doc_id	sent_index	relation_id	relation	trigger	trigger_offset	arg_num	arg_head	arg_protein	arg_domain	arg_site	arg_sugar	arg_head_offset	arg_base_np	arg_base_np_offset	arg_np	arg_np_offset	sent_text
28186505	6	0	theme	death	956:960	arg1	receptors					962:970	human TRAIL death receptors	944:970	human TRAIL death receptors	944:970	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	3	1	theme	mouse	502:506	arg1	TRAIL-R					508:514	mouse TRAIL-R	502:514	mouse TRAIL-R	502:514	Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts.
28186505	4	2	theme	apoptotic	590:598	arg1	signaling					600:608	Defective apoptotic signaling	580:608	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors	580:644	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	5	3	theme	TRAIL	803:807	arg1	N-glyc					818:823	TRAIL receptor N-glyc	803:823	TRAIL receptor N-glyc	803:823	Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies.
28186505	5	4	theme	receptor	809:816	arg1	N-glyc					818:823	TRAIL receptor N-glyc	803:823	TRAIL receptor N-glyc	803:823	Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies.
28186505	3	5	theme	TRAIL-R	508:514	arg1	mutants					478:484	N-glyc-defective mutants	461:484	N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R	461:514	Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts.
28186505	4	6	theme	Defective	580:588	arg1	signaling					600:608	Defective apoptotic signaling	580:608	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors	580:644	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	6	7	theme	human	944:948	arg1	receptors					962:970	human TRAIL death receptors	944:970	human TRAIL death receptors	944:970	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	2	8	theme	important	288:296	arg1	role					309:312	an important regulatory role	285:312	an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans	285:441	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	3	9	theme	wild-type	556:564	arg1	counterparts					566:577	their wild-type counterparts	550:577	their wild-type counterparts	550:577	Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts.
28186505	7	10	theme	virus-mediated	1255:1268	arg1	inhibition					1270:1279	virus-mediated inhibition	1255:1279	virus-mediated inhibition	1255:1279	Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.
28186505	4	11	theme	reduced	740:746	arg1	affinity					762:769	reduced TRAIL-binding affinity	740:769	reduced TRAIL-binding affinity	740:769	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	3	12	theme	N-glyc-defective	461:476	arg1	mutants					478:484	N-glyc-defective mutants	461:484	N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R	461:514	Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts.
28186505	2	13	dep	-mediated	371:379	arg1	receptor					352:359	mouse TRAIL receptor	340:359	mouse TRAIL receptor	340:359	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	1	14	theme	agonist	175:181	arg1	TRAIL-R2					207:214	TRAIL-R2	207:214	TRAIL-R2	207:214	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	1	14	theme	agonist	175:181	arg1	TRAIL-R1					194:201	TRAIL-R1	194:201	TRAIL-R1	194:201	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	1	14	theme	agonist	175:181	arg1	receptors					183:191	two agonist receptors	171:191	two agonist receptors	171:191	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	5	15	theme	immune	833:838	arg1	strategies					848:857	immune evasion strategies	833:857	immune evasion strategies	833:857	Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies.
28186505	6	16	theme	cell-surface	917:928	arg1	expression					930:939	cell-surface expression	917:939	cell-surface expression of human TRAIL death receptors	917:970	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	5	17	theme	evasion	840:846	arg1	strategies					848:857	immune evasion strategies	833:857	immune evasion strategies	833:857	Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies.
28186505	4	18	theme	N-glyc-deficient	613:628	arg1	receptors					636:644	N-glyc-deficient TRAIL receptors	613:644	N-glyc-deficient TRAIL receptors	613:644	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	4	19	theme	receptor	678:685	arg1	aggregation					687:697	lower TRAIL receptor aggregation	666:697	lower TRAIL receptor aggregation	666:697	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	2	20	theme	N-glycans	433:441	arg1	devoid					423:428	devoid	423:428	devoid	423:428	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	4	21	theme	reduced	703:709	arg1	formation					716:724	reduced DISC formation	703:724	reduced DISC formation	703:724	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	6	22	theme	TRAIL	950:954	arg1	receptors					962:970	human TRAIL death receptors	944:970	human TRAIL death receptors	944:970	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	1	23	theme	TNF-related	95:105	arg1	APO2L/TRAIL					82:92	APO2L/TRAIL	82:92	APO2L/TRAIL (TNF-related apoptosis-inducing ligand)	82:132	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	1	23	theme	TNF-related	95:105	arg1	ligand					126:131	TNF-related apoptosis-inducing ligand	95:131	TNF-related apoptosis-inducing ligand	95:131	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	0	24	theme	TRAIL-R	25:31	arg1	N-glycosylation					0:14	N-glycosylation	0:14	N-glycosylation of mouse TRAIL-R and human TRAIL-R1	0:50	N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
28186505	1	25	theme	apoptosis-inducing	107:124	arg1	APO2L/TRAIL					82:92	APO2L/TRAIL	82:92	APO2L/TRAIL (TNF-related apoptosis-inducing ligand)	82:132	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	1	25	theme	apoptosis-inducing	107:124	arg1	ligand					126:131	TNF-related apoptosis-inducing ligand	95:131	TNF-related apoptosis-inducing ligand	95:131	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	0	26	gly	N-glycosylation	0:14	arg1	TRAIL-R					25:31	mouse TRAIL-R	19:31	mouse TRAIL-R	19:31	N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
28186505	0	26	gly	N-glycosylation	0:14	arg1	TRAIL-R1					43:50	human TRAIL-R1	37:50	human TRAIL-R1	37:50	N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
28186505	0	27	theme	mouse	19:23	arg1	TRAIL-R					25:31	mouse TRAIL-R	19:31	mouse TRAIL-R	19:31	N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
28186505	6	28	theme	affinity	1003:1010	arg1	TRAIL-R1					1012:1019	significant higher affinity TRAIL-R1	984:1019	significant higher affinity TRAIL-R1 lacking N-glyc	984:1034	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	2	29	theme	regulatory	298:307	arg1	role					309:312	an important regulatory role	285:312	an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans	285:441	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	1	30	theme	tumor	151:155	arg1	cells					157:161	tumor cells	151:161	tumor cells	151:161	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
28186505	0	31	theme	human	37:41	arg1	TRAIL-R1					43:50	human TRAIL-R1	37:50	human TRAIL-R1	37:50	N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
28186505	2	32	theme	N-linked	242:249	arg1	N-glyc					266:271	N-glyc	266:271	N-glyc	266:271	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	2	32	theme	N-linked	242:249	arg1	glycosylation					251:263	N-linked glycosylation	242:263	N-linked glycosylation (N-glyc)	242:272	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	4	33	theme	TRAIL	672:676	arg1	aggregation					687:697	lower TRAIL receptor aggregation	666:697	lower TRAIL receptor aggregation	666:697	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	6	34	theme	receptor	1126:1133	arg1	inhibition					1135:1144	receptor inhibition	1126:1144	receptor inhibition by UL141	1126:1153	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	6	35	theme	significant	984:994	arg1	TRAIL-R1					1012:1019	significant higher affinity TRAIL-R1	984:1019	significant higher affinity TRAIL-R1 lacking N-glyc	984:1034	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	7	36	theme	TRAIL-R1	1207:1214	arg1	N-glyc					1197:1202	N-glyc	1197:1202	N-glyc of TRAIL-R1	1197:1214	Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.
28186505	6	37	dep	significant	984:994	arg1	higher					996:1001	higher	996:1001	higher	996:1001	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	6	38	theme	sugar	1058:1062	arg1	modification					1064:1075	this sugar modification	1053:1075	this sugar modification	1053:1075	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	4	39	theme	lower	666:670	arg1	aggregation					687:697	lower TRAIL receptor aggregation	666:697	lower TRAIL receptor aggregation	666:697	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	6	40	theme	UL141	886:890	arg1	protein					892:898	The cytomegalovirus (CMV) UL141 protein	860:898	The cytomegalovirus (CMV) UL141 protein	860:898	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	3	41	theme	TRAIL-R1	489:496	arg1	mutants					478:484	N-glyc-defective mutants	461:484	N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R	461:514	Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts.
28186505	0	42	theme	TRAIL-R1	43:50	arg1	N-glycosylation					0:14	N-glycosylation	0:14	N-glycosylation of mouse TRAIL-R and human TRAIL-R1	0:50	N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
28186505	2	43	theme	TRAIL	346:350	arg1	receptor					352:359	mouse TRAIL receptor	340:359	mouse TRAIL receptor	340:359	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	2	44	theme	mouse	340:344	arg1	receptor					352:359	mouse TRAIL receptor	340:359	mouse TRAIL receptor	340:359	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	4	45	theme	TRAIL	630:634	arg1	receptors					636:644	N-glyc-deficient TRAIL receptors	613:644	N-glyc-deficient TRAIL receptors	613:644	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	4	46	theme	DISC	711:714	arg1	formation					716:724	reduced DISC formation	703:724	reduced DISC formation	703:724	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	4	47	theme	TRAIL-binding	748:760	arg1	affinity					762:769	reduced TRAIL-binding affinity	740:769	reduced TRAIL-binding affinity	740:769	Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity.
28186505	6	48	theme	cytomegalovirus	864:878	arg1	protein					892:898	The cytomegalovirus (CMV) UL141 protein	860:898	The cytomegalovirus (CMV) UL141 protein	860:898	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	2	49	theme	-mediated	371:379	arg1	apoptosis					381:389	mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis	340:389	mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis	340:389	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	2	50	link	N-linked	242:249	arg1	N-glyc					266:271	N-glyc	266:271	N-glyc	266:271	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	2	50	link	N-linked	242:249	arg1	glycosylation					251:263	N-linked glycosylation	242:263	N-linked glycosylation (N-glyc)	242:272	We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans.
28186505	0	51	theme	TRAIL-induced	61:73	arg1	death					75:79	TRAIL-induced death	61:79	TRAIL-induced death	61:79	N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.
28186505	6	52	theme	receptors	962:970	arg1	expression					930:939	cell-surface expression	917:939	cell-surface expression of human TRAIL death receptors	917:970	The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141.
28186505	7	53	theme	TRAIL	1225:1229	arg1	signaling					1231:1239	TRAIL signaling	1225:1239	TRAIL signaling	1225:1239	Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition.
28186505	1	54	theme	cells	157:161	arg1	death					142:146	death	142:146	death of tumor cells	142:161	APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2.
30002126	9	0	theme	kidney-derived	1417:1430	arg1	VIII					1439:1442	baby hamster kidney-derived factor VIII	1404:1442	baby hamster kidney-derived factor VIII	1404:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	7	1	theme	hamster	1206:1212	arg1	VIII					1236:1239	baby hamster kidney-derived factor VIII	1201:1239	baby hamster kidney-derived factor VIII in naive hemophilia A mice	1201:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	3	2	theme	mouse	540:544	arg1	models					546:551	two hemophilia A mouse models	523:551	two hemophilia A mouse models	523:551	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	1	3	theme	recombinant	266:276	arg1	VIII					285:288	recombinant factor VIII	266:288	recombinant factor VIII produced in baby hamster kidney cells	266:326	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	5	4	gly	sialylation	952:962	arg1	sites					993:997	glycan sites	986:997	glycan sites	986:997	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	10	5	theme	hemophilia	1906:1915	arg1	A					1917:1917	hemophilia A	1906:1917	hemophilia A	1906:1917	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	10	6	theme	ovary	1677:1681	arg1	cells					1683:1687	Chinese hamster ovary cells	1661:1687	Chinese hamster ovary cells	1661:1687	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	3	7	theme	cell-derived	574:585	arg1	VIII					594:597	baby hamster kidney cell-derived factor VIII	554:597	baby hamster kidney cell-derived factor VIII	554:597	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	0	8	link	N-linked	0:7	arg1	glycosylation					9:21	N-linked glycosylation	0:21	N-linked glycosylation	0:21	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	4	9	theme	factor	705:710	arg1	VIII					712:715	factor VIII	705:715	factor VIII produced in baby hamster kidney cells	705:753	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	10	10	theme	Chinese	1661:1667	arg1	cells					1683:1687	Chinese hamster ovary cells	1661:1687	Chinese hamster ovary cells	1661:1687	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	7	11	theme	IgM	1185:1187	arg1	levels					1175:1180	increased levels	1165:1180	increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice	1165:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	3	12	theme	hamster	559:565	arg1	kidney					567:572	baby hamster kidney	554:572	baby hamster kidney cell-derived factor VIII	554:597	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	10	13	theme	mouse	1890:1894	arg1	models					1896:1901	these mouse models	1884:1901	these mouse models	1884:1901	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	8	14	theme	IgM	1297:1299	arg1	binding					1301:1307	IgM binding	1297:1307	IgM binding	1297:1307	De-N-glycosylation enhanced IgM binding, suggesting that N-glycan occupancy masks epitopes.
30002126	1	15	theme	ovary	393:397	arg1	cells					399:403	Chinese hamster ovary cells	377:403	Chinese hamster ovary cells	377:403	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	1	16	theme	hemophilia	199:208	arg1	treatment					179:187	the treatment	175:187	the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells	175:403	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	10	17	theme	N-linked	1723:1730	arg1	sites					1746:1750	N-linked glycosylation sites	1723:1750	N-linked glycosylation sites	1723:1750	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	7	18	theme	naive	1244:1248	arg1	mice					1263:1266	naive hemophilia A mice	1244:1266	naive hemophilia A mice	1244:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	5	19	from	differences	915:925	arg1	glycans					943:949	high-mannose glycans	930:949	high-mannose glycans	930:949	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	5	19	from	differences	915:925	arg1	occupancy					973:981	the occupancy	969:981	the occupancy of glycan sites	969:997	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	5	19	from	differences	915:925	arg1	sialylation					952:962	sialylation	952:962	sialylation	952:962	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	1	20	theme	Recent	213:218	arg1	evidence					236:243	A. Recent epidemiological evidence	210:243	A. Recent epidemiological evidence	210:243	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	3	21	theme	immune	619:624	arg1	response					626:633	a stronger immune response	608:633	a stronger immune response compared Chinese hamster ovary cell-derived factor VIII	608:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	5	22	theme	glycan	986:991	arg1	sites					993:997	glycan sites	986:997	glycan sites	986:997	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	10	23	from	clearance	1852:1860	arg1	models					1896:1901	these mouse models	1884:1901	these mouse models	1884:1901	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	6	24	theme	Factor	1000:1005	arg1	VIII					1007:1010	Factor VIII	1000:1010	Factor VIII desialylation	1000:1024	Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression.
30002126	5	25	gly	occupancy	973:981	arg2	sites					993:997	glycan sites	986:997	glycan sites	986:997	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	5	26	link	N-linked	889:896	arg1	glycans					898:904	total N-linked glycans	883:904	total N-linked glycans	883:904	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	10	27	from	immunogenicity	1866:1879	arg1	models					1896:1901	these mouse models	1884:1901	these mouse models	1884:1901	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	5	28	theme	sites	993:997	arg1	glycans					943:949	high-mannose glycans	930:949	high-mannose glycans	930:949	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	5	28	theme	sites	993:997	arg1	occupancy					973:981	the occupancy	969:981	the occupancy of glycan sites	969:997	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	5	28	theme	sites	993:997	arg1	sialylation					952:962	sialylation	952:962	sialylation	952:962	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	9	29	located	observed	1454:1461	arg2	levels					1370:1375	Elevated levels	1361:1375	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII	1361:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	9	29	located	observed	1454:1461	arg1	individuals					1474:1484	healthy individuals	1466:1484	healthy individuals	1466:1484	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	4	30	theme	baby	729:732	arg1	kidney					742:747	baby hamster kidney	729:747	baby hamster kidney cells	729:753	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	0	31	theme	factor	73:78	arg1	VIII					80:83	recombinant human factor VIII	55:83	recombinant human factor VIII	55:83	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	9	32	theme	IgM	1380:1382	arg1	levels					1370:1375	Elevated levels	1361:1375	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII	1361:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	5	33	theme	N-linked	889:896	arg1	glycans					898:904	total N-linked glycans	883:904	total N-linked glycans	883:904	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	4	34	theme	kidney	742:747	arg1	cells					749:753	baby hamster kidney cells	729:753	baby hamster kidney cells	729:753	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	1	35	theme	factor	353:358	arg1	VIII					360:363	factor VIII	353:363	factor VIII produced in Chinese hamster ovary cells	353:403	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	3	36	theme	cell-derived	666:677	arg1	VIII					686:689	Chinese hamster ovary cell-derived factor VIII	644:689	Chinese hamster ovary cell-derived factor VIII	644:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	10	37	gly	glycosylation	1732:1744	arg2	sites					1746:1750	N-linked glycosylation sites	1723:1750	N-linked glycosylation sites	1723:1750	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	4	38	theme	Willebrand	823:832	arg1	factor					834:839	von Willebrand factor	819:839	von Willebrand factor	819:839	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	0	39	theme	A	99:99	arg1	mice					101:104	hemophilia A mice	88:104	hemophilia A mice	88:104	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	6	40	theme	murine	1055:1060	arg1	splenocytes					1062:1072	murine splenocytes	1055:1072	murine splenocytes	1055:1072	Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression.
30002126	2	41	theme	Glycosylation	406:418	arg1	differences					420:430	Glycosylation differences	406:430	Glycosylation differences	406:430	Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates.
30002126	1	42	theme	Chinese	377:383	arg1	cells					399:403	Chinese hamster ovary cells	377:403	Chinese hamster ovary cells	377:403	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	0	43	from	immunogenicity	37:50	arg1	mice					101:104	hemophilia A mice	88:104	hemophilia A mice	88:104	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	10	44	theme	factor	1569:1574	arg1	VIII					1576:1579	factor VIII	1569:1579	factor VIII produced in baby hamster kidney cells	1569:1617	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	0	45	theme	N-linked	0:7	arg1	glycosylation					9:21	N-linked glycosylation	0:21	N-linked glycosylation	0:21	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	9	46	theme	factor	1432:1437	arg1	VIII					1439:1442	baby hamster kidney-derived factor VIII	1404:1442	baby hamster kidney-derived factor VIII	1404:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	4	47	from	circulation	792:802	arg1	clearance					777:785	accelerated clearance	765:785	accelerated clearance from circulation independent of von Willebrand factor	765:839	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	10	48	theme	kidney	1606:1611	arg1	cells					1613:1617	baby hamster kidney cells	1593:1617	baby hamster kidney cells	1593:1617	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	7	49	theme	hemophilia	1250:1259	arg1	mice					1263:1266	naive hemophilia A mice	1244:1266	naive hemophilia A mice	1244:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	1	50	theme	baby	302:305	arg1	kidney					315:320	baby hamster kidney	302:320	baby hamster kidney cells	302:326	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	1	51	theme	Immune	107:112	arg1	responses					114:122	Immune responses	107:122	Immune responses to factor VIII	107:137	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	2	52	theme	concentrates	506:517	arg1	immunogenicity					472:485	the immunogenicity	468:485	the immunogenicity of these synthetic concentrates	468:517	Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates.
30002126	10	53	theme	baby	1593:1596	arg1	kidney					1606:1611	baby hamster kidney	1593:1611	baby hamster kidney cells	1593:1617	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	1	54	theme	kidney	315:320	arg1	cells					322:326	baby hamster kidney cells	302:326	baby hamster kidney cells	302:326	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	6	55	theme	co-stimulatory	1106:1119	arg1	expression					1130:1139	surface co-stimulatory molecule expression	1098:1139	surface co-stimulatory molecule expression	1098:1139	Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression.
30002126	7	56	theme	kidney-derived	1214:1227	arg1	VIII					1236:1239	baby hamster kidney-derived factor VIII	1201:1239	baby hamster kidney-derived factor VIII in naive hemophilia A mice	1201:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	10	57	theme	complexes	1810:1818	arg1	formation					1765:1773	the formation	1761:1773	the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A	1761:1917	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	7	58	theme	factor	1229:1234	arg1	VIII					1236:1239	baby hamster kidney-derived factor VIII	1201:1239	baby hamster kidney-derived factor VIII in naive hemophilia A mice	1201:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	9	59	theme	healthy	1466:1472	arg1	individuals					1474:1484	healthy individuals	1466:1484	healthy individuals	1466:1484	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	3	60	theme	hamster	652:658	arg1	ovary					660:664	Chinese hamster ovary	644:664	Chinese hamster ovary cell-derived factor VIII	644:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	10	61	theme	VIII	1798:1801	arg1	complexes					1810:1818	IgM- and IgG-factor VIII immune complexes	1778:1818	IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A	1778:1917	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	1	62	theme	epidemiological	220:234	arg1	evidence					236:243	A. Recent epidemiological evidence	210:243	A. Recent epidemiological evidence	210:243	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	10	63	theme	enhanced	1843:1850	arg1	clearance					1852:1860	clearance	1852:1860	clearance	1852:1860	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	5	64	theme	mass	853:856	arg1	analysis					871:878	Lectin and mass spectrometry analysis	842:878	analysis	871:878	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	7	65	theme	baby	1201:1204	arg1	VIII					1236:1239	baby hamster kidney-derived factor VIII	1201:1239	baby hamster kidney-derived factor VIII in naive hemophilia A mice	1201:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	3	66	theme	A	538:538	arg1	models					546:551	two hemophilia A mouse models	523:551	two hemophilia A mouse models	523:551	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	9	67	theme	IgG	1520:1522	arg1	binding					1524:1530	IgG binding	1520:1530	IgG binding	1520:1530	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	7	68	theme	specific	1189:1196	arg1	IgM					1185:1187	IgM	1185:1187	IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice	1185:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	3	69	theme	kidney	567:572	arg1	VIII					594:597	baby hamster kidney cell-derived factor VIII	554:597	baby hamster kidney cell-derived factor VIII	554:597	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	1	70	theme	factor	278:283	arg1	VIII					285:288	recombinant factor VIII	266:288	recombinant factor VIII produced in baby hamster kidney cells	266:326	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	10	71	theme	hamster	1669:1675	arg1	cells					1683:1687	Chinese hamster ovary cells	1661:1687	Chinese hamster ovary cells	1661:1687	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	3	72	theme	baby	554:557	arg1	kidney					567:572	baby hamster kidney	554:572	baby hamster kidney cell-derived factor VIII	554:597	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	5	73	theme	high-mannose	930:941	arg1	glycans					943:949	high-mannose glycans	930:949	high-mannose glycans	930:949	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	5	74	theme	spectrometry	858:869	arg1	analysis					871:878	Lectin and mass spectrometry analysis	842:878	analysis	871:878	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	8	75	theme	N-glycan	1326:1333	arg1	occupancy					1335:1343	N-glycan occupancy	1326:1343	N-glycan occupancy	1326:1343	De-N-glycosylation enhanced IgM binding, suggesting that N-glycan occupancy masks epitopes.
30002126	10	76	theme	incomplete	1699:1708	arg1	occupancy					1710:1718	incomplete occupancy	1699:1718	incomplete occupancy of N-linked glycosylation sites	1699:1750	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	7	77	theme	increased	1165:1173	arg1	levels					1175:1180	increased levels	1165:1180	increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice	1165:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	9	78	theme	IgG	1388:1390	arg1	levels					1370:1375	Elevated levels	1361:1375	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII	1361:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	0	79	theme	recombinant	55:65	arg1	VIII					80:83	recombinant human factor VIII	55:83	recombinant human factor VIII	55:83	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	10	80	link	N-linked	1723:1730	arg1	sites					1746:1750	N-linked glycosylation sites	1723:1750	N-linked glycosylation sites	1723:1750	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	3	81	theme	factor	587:592	arg1	VIII					594:597	baby hamster kidney cell-derived factor VIII	554:597	baby hamster kidney cell-derived factor VIII	554:597	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	1	82	theme	severe	192:197	arg1	hemophilia					199:208	severe hemophilia	192:208	severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells	192:403	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	10	83	theme	glycosylation	1732:1744	arg1	sites					1746:1750	N-linked glycosylation sites	1723:1750	N-linked glycosylation sites	1723:1750	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	10	84	theme	immune	1803:1808	arg1	complexes					1810:1818	IgM- and IgG-factor VIII immune complexes	1778:1818	IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A	1778:1917	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	7	85	link	kidney-derived	1214:1227	arg1	VIII					1236:1239	baby hamster kidney-derived factor VIII	1201:1239	baby hamster kidney-derived factor VIII in naive hemophilia A mice	1201:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	1	86	theme	A.	210:211	arg1	evidence					236:243	A. Recent epidemiological evidence	210:243	A. Recent epidemiological evidence	210:243	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	3	87	theme	stronger	610:617	arg1	response					626:633	a stronger immune response	608:633	a stronger immune response compared Chinese hamster ovary cell-derived factor VIII	608:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	6	88	theme	VIII	1007:1010	arg1	desialylation					1012:1024	Factor VIII desialylation	1000:1024	Factor VIII desialylation	1000:1024	Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression.
30002126	9	89	theme	Elevated	1361:1368	arg1	levels					1370:1375	Elevated levels	1361:1375	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII	1361:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	3	90	theme	ovary	660:664	arg1	VIII					686:689	Chinese hamster ovary cell-derived factor VIII	644:689	Chinese hamster ovary cell-derived factor VIII	644:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	1	91	theme	factor	127:132	arg1	VIII					134:137	factor VIII	127:137	factor VIII	127:137	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	6	92	theme	surface	1098:1104	arg1	expression					1130:1139	surface co-stimulatory molecule expression	1098:1139	surface co-stimulatory molecule expression	1098:1139	Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression.
30002126	4	93	theme	accelerated	765:775	arg1	clearance					777:785	accelerated clearance	765:785	accelerated clearance from circulation independent of von Willebrand factor	765:839	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	0	94	theme	VIII	80:83	arg1	immunogenicity					37:50	the immunogenicity	33:50	the immunogenicity of recombinant human factor VIII in hemophilia A mice	33:104	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	3	95	theme	Chinese	644:650	arg1	ovary					660:664	Chinese hamster ovary	644:664	Chinese hamster ovary cell-derived factor VIII	644:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	5	96	theme	glycans	898:904	arg1	analysis					871:878	Lectin and mass spectrometry analysis	842:878	analysis	871:878	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	0	97	theme	hemophilia	88:97	arg1	mice					101:104	hemophilia A mice	88:104	hemophilia A mice	88:104	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	1	98	theme	greatest	150:157	arg1	complication					159:170	the greatest complication	146:170	the greatest complication	146:170	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	6	99	theme	dendritic	1077:1085	arg1	cells					1087:1091	dendritic cells	1077:1091	dendritic cells	1077:1091	Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression.
30002126	7	100	from	VIII	1236:1239	arg1	mice					1263:1266	naive hemophilia A mice	1244:1266	naive hemophilia A mice	1244:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	4	101	theme	hamster	734:740	arg1	kidney					742:747	baby hamster kidney	729:747	baby hamster kidney cells	729:753	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	9	102	theme	specific	1392:1399	arg1	IgM					1380:1382	IgM	1380:1382	IgM	1380:1382	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	10	103	gly	occupancy	1710:1718	arg2	sites					1746:1750	N-linked glycosylation sites	1723:1750	N-linked glycosylation sites	1723:1750	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	4	104	theme	von	819:821	arg1	factor					834:839	von Willebrand factor	819:839	von Willebrand factor	819:839	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	9	105	theme	baby	1404:1407	arg1	VIII					1439:1442	baby hamster kidney-derived factor VIII	1404:1442	baby hamster kidney-derived factor VIII	1404:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	9	106	link	kidney-derived	1417:1430	arg1	VIII					1439:1442	baby hamster kidney-derived factor VIII	1404:1442	baby hamster kidney-derived factor VIII	1404:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	3	107	link	cell-derived	574:585	arg1	VIII					594:597	baby hamster kidney cell-derived factor VIII	554:597	baby hamster kidney cell-derived factor VIII	554:597	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	4	108	theme	factor	834:839	arg1	independent					804:814	independent	804:814	independent	804:814	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	7	109	theme	A	1261:1261	arg1	mice					1263:1266	naive hemophilia A mice	1244:1266	naive hemophilia A mice	1244:1266	We did however observe increased levels of IgM specific to baby hamster kidney-derived factor VIII in naive hemophilia A mice.
30002126	1	110	theme	hamster	385:391	arg1	cells					399:403	Chinese hamster ovary cells	377:403	Chinese hamster ovary cells	377:403	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	10	111	theme	sites	1746:1750	arg1	occupancy					1710:1718	incomplete occupancy	1699:1718	incomplete occupancy of N-linked glycosylation sites	1699:1750	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	5	112	theme	total	883:887	arg1	glycans					898:904	total N-linked glycans	883:904	total N-linked glycans	883:904	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	3	113	link	cell-derived	666:677	arg1	VIII					686:689	Chinese hamster ovary cell-derived factor VIII	644:689	Chinese hamster ovary cell-derived factor VIII	644:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	10	114	theme	hamster	1598:1604	arg1	kidney					1606:1611	baby hamster kidney	1593:1611	baby hamster kidney cells	1593:1617	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	4	115	theme	independent	804:814	arg1	circulation					792:802	circulation	792:802	circulation independent of von Willebrand factor	792:839	Furthermore, factor VIII produced in baby hamster kidney cells exhibited accelerated clearance from circulation independent of von Willebrand factor.
30002126	10	116	theme	IgM-	1778:1781	arg1	complexes					1810:1818	IgM- and IgG-factor VIII immune complexes	1778:1818	IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A	1778:1917	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	5	117	theme	Lectin	842:847	arg1	analysis					871:878	Lectin and mass spectrometry analysis	842:878	analysis	871:878	Lectin and mass spectrometry analysis of total N-linked glycans revealed differences in high-mannose glycans, sialylation, and the occupancy of glycan sites.
30002126	1	118	theme	hamster	307:313	arg1	kidney					315:320	baby hamster kidney	302:320	baby hamster kidney cells	302:326	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30002126	6	119	theme	molecule	1121:1128	arg1	expression					1130:1139	surface co-stimulatory molecule expression	1098:1139	surface co-stimulatory molecule expression	1098:1139	Factor VIII desialylation did not influence binding to murine splenocytes or dendritic cells, nor surface co-stimulatory molecule expression.
30002126	2	120	theme	synthetic	496:504	arg1	concentrates					506:517	these synthetic concentrates	490:517	these synthetic concentrates	490:517	Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates.
30002126	3	121	theme	factor	679:684	arg1	VIII					686:689	Chinese hamster ovary cell-derived factor VIII	644:689	Chinese hamster ovary cell-derived factor VIII	644:689	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	0	122	theme	human	67:71	arg1	VIII					80:83	recombinant human factor VIII	55:83	recombinant human factor VIII	55:83	N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.
30002126	9	123	theme	hamster	1409:1415	arg1	VIII					1439:1442	baby hamster kidney-derived factor VIII	1404:1442	baby hamster kidney-derived factor VIII	1404:1442	Elevated levels of IgM and IgG specific to baby hamster kidney-derived factor VIII were also observed in healthy individuals, and de-N-glycosylation increased IgG binding.
30002126	3	124	theme	hemophilia	527:536	arg1	models					546:551	two hemophilia A mouse models	523:551	two hemophilia A mouse models	523:551	In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII.
30002126	10	125	theme	A	1917:1917	arg1	immunogenicity					1866:1879	immunogenicity	1866:1879	immunogenicity	1866:1879	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	10	125	theme	A	1917:1917	arg1	clearance					1852:1860	clearance	1852:1860	clearance	1852:1860	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	10	126	theme	IgG-factor	1787:1796	arg1	VIII					1798:1801	IgG-factor VIII	1787:1801	IgG-factor VIII	1787:1801	Collectively, our data suggest that factor VIII produced in baby hamster kidney cells is more immunogenic than that produced in Chinese hamster ovary cells, and that incomplete occupancy of N-linked glycosylation sites leads to the formation of IgM- and IgG-factor VIII immune complexes that contribute to the enhanced clearance and immunogenicity in these mouse models of hemophilia A.
30002126	1	127	dep	hemophilia	199:208	arg1	highlighted					249:259	highlighted	249:259	has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells	245:403	Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells.
30042931	7	0	from	proteins	1334:1341	arg1	patterns					1290:1297	the patterns	1286:1297	the patterns of N-linked glycosylation on JEV E proteins	1286:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	7	1	theme	N-linked	1302:1309	arg1	glycosylation					1311:1323	N-linked glycosylation	1302:1323	N-linked glycosylation on JEV E proteins	1302:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	6	2	theme	enhanced	1127:1134	arg1	binding					1144:1150	enhanced DC-SIGN binding	1127:1150	enhanced DC-SIGN binding	1127:1150	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	4	3	gly	glycosylation	811:823	arg1	mutant					856:861	the G0 mutant	849:861	the G0 mutant (E-N154A) with non-glycosylation	849:894	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	3	gly	glycosylation	811:823	arg1	E-N154A					864:870	E-N154A	864:870	E-N154A	864:870	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	3	gly	glycosylation	811:823	arg1	E-D67N/N154A					792:803	E-D67N/N154A	792:803	E-D67N/N154A	792:803	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	3	gly	glycosylation	811:823	arg1	mutant					784:789	the G1 mutant	777:789	the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site	777:842	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	6	4	theme	glycosylation	1262:1274	arg1	glycosylation					1262:1274	glycosylation	1262:1274	glycosylation	1262:1274	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	6	4	theme	glycosylation	1262:1274	arg1	site					1254:1257	this G1 site	1246:1257	this G1 site of glycosylation	1246:1274	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	1	5	theme	envelope	177:184	arg1	protein					190:196	The major structural envelope (E) protein	156:196	The major structural envelope (E) protein of Japanese encephalitis virus (JEV)	156:233	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	1	6	theme	E	187:187	arg1	protein					190:196	The major structural envelope (E) protein	156:196	The major structural envelope (E) protein of Japanese encephalitis virus (JEV)	156:233	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	7	7	link	N-linked	1302:1309	arg1	glycosylation					1311:1323	N-linked glycosylation	1302:1323	N-linked glycosylation on JEV E proteins	1302:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	6	8	theme	brain	1184:1188	arg1	invasion					1190:1197	reduced brain invasion	1176:1197	reduced brain invasion	1176:1197	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	7	9	with	interaction	1360:1370	arg1	lectins					1386:1392	cellular lectins	1377:1392	cellular lectins	1377:1392	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	4	10	theme	G1	836:837	arg1	site					839:842	G1 site	836:842	G1 site	836:842	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	0	11	theme	Viral	134:138	arg1	Invasion					146:153	Viral Brain Invasion	134:153	Viral Brain Invasion	134:153	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	3	12	theme	recombinant	516:526	arg1	JEVs					528:531	three recombinant JEVs	510:531	three recombinant JEVs with different glycosylation patterns on the E protein	510:586	We generated three recombinant JEVs with different glycosylation patterns on the E protein.
30042931	1	13	theme	Japanese	201:208	arg1	JEV					230:232	JEV	230:232	JEV	230:232	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	1	13	theme	Japanese	201:208	arg1	virus					223:227	Japanese encephalitis virus	201:227	Japanese encephalitis virus (JEV)	201:233	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	7	14	from	glycosylation	1311:1323	arg1	proteins					1334:1341	JEV E proteins	1328:1341	JEV E proteins	1328:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	0	15	theme	Invasion	146:153	arg1	Ability					123:129	the Ability	119:129	the Ability of Viral Brain Invasion	119:153	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	4	16	with	mutant	784:789	arg1	non-glycosylation					878:894	non-glycosylation	878:894	non-glycosylation	878:894	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	16	with	mutant	784:789	arg1	glycosylation					811:823	glycosylation	811:823	glycosylation shifted to G1 site	811:842	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	17	theme	G2	630:631	arg1	glycosylation					633:645	G2 glycosylation	630:645	G2 glycosylation	630:645	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	3	18	theme	glycosylation	548:560	arg1	patterns					562:569	different glycosylation patterns	538:569	different glycosylation patterns	538:569	We generated three recombinant JEVs with different glycosylation patterns on the E protein.
30042931	4	19	theme	wild-type	606:614	arg1	JEV					621:623	wild-type (WT) JEV	606:623	wild-type (WT) JEV	606:623	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	7	20	theme	viral	1412:1416	arg1	replication					1418:1428	viral replication	1412:1428	viral replication	1412:1428	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	2	21	theme	glycosylation	440:452	arg1	sites					454:458	two glycosylation sites	436:458	two glycosylation sites	436:458	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	0	22	theme	Encephalitis	75:86	arg1	Virus					88:92	Japanese Encephalitis Virus	66:92	Japanese Encephalitis Virus Envelope Protein	66:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	5	23	theme	in	983:984	arg1	replication					998:1008	potent in vitro viral replication	976:1008	potent in vitro viral replication	976:1008	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	1	24	theme	major	160:164	arg1	protein					190:196	The major structural envelope (E) protein	156:196	The major structural envelope (E) protein of Japanese encephalitis virus (JEV)	156:233	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	4	25	theme	culture	664:670	arg1	cells					672:676	culture cells	664:676	culture cells as well as neurovirulence and neuroinvasiveness in challenged mice	664:743	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	0	26	theme	Envelope	94:101	arg1	Protein					103:109	Japanese Encephalitis Virus Envelope Protein	66:109	Japanese Encephalitis Virus Envelope Protein	66:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	2	27	contain	has	338:340	arg2	site					369:372	one N-linked glycosylation site	342:372	one N-linked glycosylation site	342:372	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	2	27	contain	has	338:340	arg1	protein					330:336	JEV E protein	324:336	JEV E protein	324:336	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	5	28	dep	in	1014:1015	arg1	vivo					1017:1020	vivo	1017:1020	vivo	1017:1020	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	0	29	theme	Extra	34:38	arg1	Glycosylation					49:61	an Extra N-Linked Glycosylation	31:61	an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein	31:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	4	30	from	growth	654:659	arg1	neurovirulence					689:702	neurovirulence	689:702	neurovirulence	689:702	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	30	from	growth	654:659	arg1	cells					672:676	culture cells	664:676	culture cells as well as neurovirulence and neuroinvasiveness in challenged mice	664:743	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	2	31	theme	dengue	409:414	arg1	protein					424:430	the related dengue virus E protein	397:430	the related dengue virus E protein	397:430	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	0	32	theme	Japanese	66:73	arg1	Virus					88:92	Japanese Encephalitis Virus	66:92	Japanese Encephalitis Virus Envelope Protein	66:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	0	33	theme	DC-SIGN	0:6	arg1	Binding					8:14	DC-SIGN Binding	0:14	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein	0:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	6	34	theme	site	1254:1257	arg1	devoid					1236:1241	devoid	1236:1241	devoid	1236:1241	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	2	35	gly	glycosylation	440:452	arg2	two					436:438	two	436:438	two	436:438	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	2	35	gly	glycosylation	440:452	arg2	sites					454:458	two glycosylation sites	436:458	two glycosylation sites	436:458	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	3	36	theme	E	578:578	arg1	protein					580:586	the E protein	574:586	the E protein	574:586	We generated three recombinant JEVs with different glycosylation patterns on the E protein.
30042931	5	37	theme	viral	992:996	arg1	replication					998:1008	potent in vitro viral replication	976:1008	potent in vitro viral replication	976:1008	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	5	38	theme	G1G2	901:904	arg1	E-D67N					914:919	E-D67N	914:919	E-D67N	914:919	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	5	38	theme	G1G2	901:904	arg1	mutant					906:911	The G1G2 mutant	897:911	The G1G2 mutant (E-D67N)	897:920	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	2	39	theme	E	422:422	arg1	protein					424:430	the related dengue virus E protein	397:430	the related dengue virus E protein	397:430	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	0	40	theme	N-Linked	40:47	arg1	Glycosylation					49:61	an Extra N-Linked Glycosylation	31:61	an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein	31:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	1	41	theme	neutralizing	299:310	arg1	antibodies					312:321	neutralizing antibodies	299:321	neutralizing antibodies	299:321	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	4	42	with	mutant	856:861	arg1	non-glycosylation					878:894	non-glycosylation	878:894	non-glycosylation	878:894	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	42	with	mutant	856:861	arg1	glycosylation					811:823	glycosylation	811:823	glycosylation shifted to G1 site	811:842	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	2	43	theme	JEV	324:326	arg1	protein					330:336	JEV E protein	324:336	JEV E protein	324:336	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	1	44	theme	encephalitis	210:221	arg1	JEV					230:232	JEV	230:232	JEV	230:232	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	1	44	theme	encephalitis	210:221	arg1	virus					223:227	Japanese encephalitis virus	201:227	Japanese encephalitis virus (JEV)	201:233	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	7	45	theme	JEV	1328:1330	arg1	proteins					1334:1341	JEV E proteins	1328:1341	JEV E proteins	1328:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	2	46	theme	glycosylation	355:367	arg1	site					369:372	one N-linked glycosylation site	342:372	one N-linked glycosylation site	342:372	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	7	47	theme	glycosylation	1311:1323	arg1	patterns					1290:1297	the patterns	1286:1297	the patterns of N-linked glycosylation on JEV E proteins	1286:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	6	48	theme	WT	1226:1227	arg1	JEV					1229:1231	WT JEV	1226:1231	WT JEV	1226:1231	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	5	49	with	mutant	906:911	arg1	E-glycosylation					928:942	E-glycosylation	928:942	E-glycosylation on both G1 and G2 sites	928:966	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	6	50	theme	DC-SIGN	1136:1142	arg1	binding					1144:1150	enhanced DC-SIGN binding	1127:1150	enhanced DC-SIGN binding	1127:1150	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	1	51	theme	cellular	247:254	arg1	binding/entry					256:268	cellular binding/entry	247:268	cellular binding/entry	247:268	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	4	52	theme	G1	781:782	arg1	E-D67N/N154A					792:803	E-D67N/N154A	792:803	E-D67N/N154A	792:803	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	52	theme	G1	781:782	arg1	mutant					784:789	the G1 mutant	777:789	the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site	777:842	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	1	53	theme	structural	166:175	arg1	protein					190:196	The major structural envelope (E) protein	156:196	The major structural envelope (E) protein of Japanese encephalitis virus (JEV)	156:233	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	2	54	link	N-linked	346:353	arg1	site					369:372	one N-linked glycosylation site	342:372	one N-linked glycosylation site	342:372	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	6	55	theme	G1	1103:1104	arg1	glycosylation					1106:1118	G1 glycosylation	1103:1118	G1 glycosylation	1103:1118	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	2	56	contain	has	432:434	arg1	protein					424:430	the related dengue virus E protein	397:430	the related dengue virus E protein	397:430	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	2	56	contain	has	432:434	arg2	sites					454:458	two glycosylation sites	436:458	two glycosylation sites	436:458	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	7	57	from	patterns	1290:1297	arg1	proteins					1334:1341	JEV E proteins	1328:1341	JEV E proteins	1328:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	0	58	theme	Brain	140:144	arg1	Invasion					146:153	Viral Brain Invasion	134:153	Viral Brain Invasion	134:153	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	6	59	theme	reduced	1176:1182	arg1	invasion					1190:1197	reduced brain invasion	1176:1197	reduced brain invasion	1176:1197	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	6	60	theme	JEV	1086:1088	arg1	mutants					1090:1096	the JEV mutants	1082:1096	the JEV mutants with G1 glycosylation	1082:1118	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	1	61	theme	antibodies	312:321	arg1	target					289:294	the primary target	277:294	the primary target of neutralizing antibodies	277:321	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	5	62	theme	G1	952:953	arg1	sites					962:966	both G1 and G2 sites	947:966	both G1 and G2 sites	947:966	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	6	63	gly	glycosylation	1106:1118	arg1	mutants					1090:1096	the JEV mutants	1082:1096	the JEV mutants with G1 glycosylation	1082:1118	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	3	64	theme	different	538:546	arg1	patterns					562:569	different glycosylation patterns	538:569	different glycosylation patterns	538:569	We generated three recombinant JEVs with different glycosylation patterns on the E protein.
30042931	4	65	from	neuroinvasiveness	708:724	arg1	mice					740:743	challenged mice	729:743	challenged mice	729:743	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	2	66	theme	G2	487:488	arg1	N153					481:484	N153	481:484	N153	481:484	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	2	66	theme	G2	487:488	arg1	site					490:493	G2 site	487:493	G2 site	487:493	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	3	67	with	JEVs	528:531	arg1	patterns					562:569	different glycosylation patterns	538:569	different glycosylation patterns	538:569	We generated three recombinant JEVs with different glycosylation patterns on the E protein.
30042931	4	68	from	neurovirulence	689:702	arg1	mice					740:743	challenged mice	729:743	challenged mice	729:743	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	6	69	with	mutants	1090:1096	arg1	glycosylation					1106:1118	G1 glycosylation	1103:1118	G1 glycosylation	1103:1118	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	4	70	theme	G0	853:854	arg1	mutant					856:861	the G0 mutant	849:861	the G0 mutant (E-N154A) with non-glycosylation	849:894	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	70	theme	G0	853:854	arg1	E-N154A					864:870	E-N154A	864:870	E-N154A	864:870	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	0	71	theme	Virus	88:92	arg1	Protein					103:109	Japanese Encephalitis Virus Envelope Protein	66:109	Japanese Encephalitis Virus Envelope Protein	66:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	5	72	theme	potent	976:981	arg1	replication					998:1008	potent in vitro viral replication	976:1008	potent in vitro viral replication	976:1008	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	4	73	from	cells	672:676	arg1	mice					740:743	challenged mice	729:743	challenged mice	729:743	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	7	74	theme	cellular	1377:1384	arg1	lectins					1386:1392	cellular lectins	1377:1392	cellular lectins	1377:1392	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	2	75	theme	G1	468:469	arg1	N67					463:465	N67	463:465	N67	463:465	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	2	75	theme	G1	468:469	arg1	site					471:474	G1 site	468:474	G1 site	468:474	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	0	76	from	Glycosylation	49:61	arg1	Protein					103:109	Japanese Encephalitis Virus Envelope Protein	66:109	Japanese Encephalitis Virus Envelope Protein	66:109	DC-SIGN Binding Contributed by an Extra N-Linked Glycosylation on Japanese Encephalitis Virus Envelope Protein Reduces the Ability of Viral Brain Invasion.
30042931	3	77	from	JEVs	528:531	arg1	protein					580:586	the E protein	574:586	the E protein	574:586	We generated three recombinant JEVs with different glycosylation patterns on the E protein.
30042931	5	78	from	E-glycosylation	928:942	arg1	sites					962:966	both G1 and G2 sites	947:966	both G1 and G2 sites	947:966	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	5	79	theme	G2	959:960	arg1	sites					962:966	both G1 and G2 sites	947:966	both G1 and G2 sites	947:966	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	4	80	dep	wild-type	606:614	arg1	WT					617:618	WT	617:618	WT	617:618	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	6	81	gly	glycosylation	1262:1274	arg2	glycosylation					1262:1274	glycosylation	1262:1274	glycosylation	1262:1274	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	6	81	gly	glycosylation	1262:1274	arg2	site					1254:1257	this G1 site	1246:1257	this G1 site of glycosylation	1246:1274	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	2	82	theme	related	401:407	arg1	protein					424:430	the related dengue virus E protein	397:430	the related dengue virus E protein	397:430	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	5	83	dep	in	983:984	arg1	vitro					986:990	vitro	986:990	vitro	986:990	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	7	84	gly	glycosylation	1311:1323	arg1	proteins					1334:1341	JEV E proteins	1328:1341	JEV E proteins	1328:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	2	85	gly	glycosylation	355:367	arg2	site					369:372	one N-linked glycosylation site	342:372	one N-linked glycosylation site	342:372	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	2	85	gly	glycosylation	355:367	arg2	one					342:344	one	342:344	one	342:344	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	4	86	theme	viral	648:652	arg1	growth					654:659	viral growth	648:659	viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice	648:743	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	6	87	theme	G1	1251:1252	arg1	glycosylation					1262:1274	glycosylation	1262:1274	glycosylation	1262:1274	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	6	87	theme	G1	1251:1252	arg1	site					1254:1257	this G1 site	1246:1257	this G1 site of glycosylation	1246:1274	Furthermore, the JEV mutants with G1 glycosylation showed enhanced DC-SIGN binding, which may then lead to reduced brain invasion and explain the reason why WT JEV is devoid of this G1 site of glycosylation.
30042931	1	88	theme	primary	281:287	arg1	target					289:294	the primary target	277:294	the primary target of neutralizing antibodies	277:321	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	2	89	theme	G2	383:384	arg1	N154					377:380	N154	377:380	N154 (G2 site)	377:390	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	2	89	theme	G2	383:384	arg1	site					386:389	G2 site	383:389	G2 site	383:389	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	7	90	theme	viral	1354:1358	arg1	interaction					1360:1370	viral interaction	1354:1370	viral interaction with cellular lectins	1354:1392	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	2	91	theme	virus	416:420	arg1	protein					424:430	the related dengue virus E protein	397:430	the related dengue virus E protein	397:430	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	4	92	theme	challenged	729:738	arg1	mice					740:743	challenged mice	729:743	challenged mice	729:743	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	2	93	theme	E	328:328	arg1	protein					330:336	JEV E protein	324:336	JEV E protein	324:336	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
30042931	5	94	theme	in	1014:1015	arg1	neurovirulence					1022:1035	in vivo neurovirulence	1014:1035	in vivo neurovirulence	1014:1035	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	5	95	gly	E-glycosylation	928:942	arg1	sites					962:966	both G1 and G2 sites	947:966	both G1 and G2 sites	947:966	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	5	95	gly	E-glycosylation	928:942	arg1	E-D67N					914:919	E-D67N	914:919	E-D67N	914:919	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	5	95	gly	E-glycosylation	928:942	arg1	mutant					906:911	The G1G2 mutant	897:911	The G1G2 mutant (E-D67N)	897:920	The G1G2 mutant (E-D67N), with E-glycosylation on both G1 and G2 sites, showed potent in vitro viral replication and in vivo neurovirulence, but reduced neuroinvasiveness.
30042931	1	96	theme	virus	223:227	arg1	protein					190:196	The major structural envelope (E) protein	156:196	The major structural envelope (E) protein of Japanese encephalitis virus (JEV)	156:233	The major structural envelope (E) protein of Japanese encephalitis virus (JEV) facilitates cellular binding/entry and is the primary target of neutralizing antibodies.
30042931	7	97	theme	E	1332:1332	arg1	proteins					1334:1341	JEV E proteins	1328:1341	JEV E proteins	1328:1341	Overall, the patterns of N-linked glycosylation on JEV E proteins may affect viral interaction with cellular lectins and contribute to viral replication and pathogenesis.
30042931	4	98	gly	non-glycosylation	878:894	arg1	mutant					856:861	the G0 mutant	849:861	the G0 mutant (E-N154A) with non-glycosylation	849:894	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	98	gly	non-glycosylation	878:894	arg1	E-N154A					864:870	E-N154A	864:870	E-N154A	864:870	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	98	gly	non-glycosylation	878:894	arg1	E-D67N/N154A					792:803	E-D67N/N154A	792:803	E-D67N/N154A	792:803	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	4	98	gly	non-glycosylation	878:894	arg1	mutant					784:789	the G1 mutant	777:789	the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site	777:842	As compared with wild-type (WT) JEV with G2 glycosylation, viral growth in culture cells as well as neurovirulence and neuroinvasiveness in challenged mice were reduced when infected with the G1 mutant (E-D67N/N154A) with glycosylation shifted to G1 site, and the G0 mutant (E-N154A) with non-glycosylation.
30042931	2	99	theme	N-linked	346:353	arg1	site					369:372	one N-linked glycosylation site	342:372	one N-linked glycosylation site	342:372	JEV E protein has one N-linked glycosylation site at N154 (G2 site), but the related dengue virus E protein has two glycosylation sites at N67 (G1 site) and N153 (G2 site).
29782851	2	0	from	effects	277:283	arg1	properties					335:344	the in vitro receptor binding properties	305:344	the in vitro receptor binding properties of Cblns	305:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	4	1	dep	glutamine	573:581	arg1	to					570:571	to	570:571	to	570:571	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	7	2	theme	transgenic	1036:1045	arg1	expression					1047:1056	transgenic expression	1036:1056	transgenic expression of wild type Cbln4 or its glycosylation mutants	1036:1104	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	2	3	theme	binding	327:333	arg1	properties					335:344	the in vitro receptor binding properties	305:344	the in vitro receptor binding properties of Cblns	305:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	1	4	theme	postsynaptic	238:249	arg1	Grid2					251:255	postsynaptic Grid2	238:255	postsynaptic Grid2	238:255	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	3	5	theme	Nrxn	463:466	arg1	binding					468:474	Nrxn binding	463:474	Nrxn binding	463:474	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	5	6	theme	N-terminal	867:876	arg1	region					878:883	the N-terminal region	863:883	the N-terminal region	863:883	These mutations did not influence subunit composition of Cbln trimeric complexes (mediated through the C1q domain) nor their assembly into hexamers (mediated by the N-terminal region).
29782851	3	7	theme	C1q	501:503	arg1	region					515:520	a region	513:520	a region involved in Grid2 binding	513:546	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	7	theme	C1q	501:503	arg1	domain					505:510	the C1q domain	497:510	the C1q domain	497:510	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	7	8	theme	mutants	1098:1104	arg1	expression					1047:1056	transgenic expression	1036:1056	transgenic expression of wild type Cbln4 or its glycosylation mutants	1036:1104	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	3	9	link	N-linked	382:389	arg1	sites					405:409	two N-linked glycosylation sites	378:409	two N-linked glycosylation sites	378:409	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	9	link	N-linked	382:389	arg1	second					484:489	second	484:489	second	484:489	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	9	link	N-linked	382:389	arg1	one					412:414	one	412:414	one	412:414	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	5	10	theme	Cbln	759:762	arg1	complexes					773:781	Cbln trimeric complexes	759:781	Cbln trimeric complexes	759:781	These mutations did not influence subunit composition of Cbln trimeric complexes (mediated through the C1q domain) nor their assembly into hexamers (mediated by the N-terminal region).
29782851	3	11	theme	N-linked	382:389	arg1	sites					405:409	two N-linked glycosylation sites	378:409	two N-linked glycosylation sites	378:409	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	11	theme	N-linked	382:389	arg1	second					484:489	second	484:489	second	484:489	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	11	theme	N-linked	382:389	arg1	one					412:414	one	412:414	one	412:414	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	6	12	theme	Cblns	960:964	arg1	interfaces					946:955	the receptor binding interfaces	925:955	the receptor binding interfaces of Cblns	925:964	Therefore, glycosylation likely masks the receptor binding interfaces of Cblns.
29782851	7	13	theme	wild	1061:1064	arg1	type					1066:1069	wild type Cbln4 or its glycosylation mutants	1061:1104	type	1066:1069	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	7	14	theme	undetectable	980:991	arg1	binding					999:1005	undetectable Grid2 binding	980:1005	undetectable Grid2 binding	980:1005	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	4	15	theme	Grid2	687:691	arg1	binding					693:699	Grid2 binding	687:699	Grid2 binding	687:699	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	1	16	theme	normal	154:159	arg1	structure					169:177	normal synapse structure	154:177	normal synapse structure	154:177	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	7	17	theme	Grid2	993:997	arg1	binding					999:1005	undetectable Grid2 binding	980:1005	undetectable Grid2 binding	980:1005	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	2	18	dep	in	309:310	arg1	vitro					312:316	vitro	312:316	vitro	312:316	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	1	19	theme	synapse	161:167	arg1	structure					169:177	normal synapse structure	154:177	normal synapse structure	154:177	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	6	20	theme	receptor	929:936	arg1	interfaces					946:955	the receptor binding interfaces	925:955	the receptor binding interfaces of Cblns	925:964	Therefore, glycosylation likely masks the receptor binding interfaces of Cblns.
29782851	7	21	dep	type	1066:1069	arg1	Cbln4					1071:1075	Cbln4	1071:1075	Cbln4	1071:1075	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	2	22	theme	glycosylation	288:300	arg1	effects					277:283	the effects	273:283	the effects of glycosylation on the in vitro receptor binding properties of Cblns	273:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	3	23	theme	glycosylation	391:403	arg1	sites					405:409	two N-linked glycosylation sites	378:409	two N-linked glycosylation sites	378:409	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	23	theme	glycosylation	391:403	arg1	second					484:489	second	484:489	second	484:489	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	23	theme	glycosylation	391:403	arg1	one					412:414	one	412:414	one	412:414	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	5	24	theme	subunit	736:742	arg1	composition					744:754	subunit composition	736:754	subunit composition of Cbln trimeric complexes (mediated through the C1q domain)	736:815	These mutations did not influence subunit composition of Cbln trimeric complexes (mediated through the C1q domain) nor their assembly into hexamers (mediated by the N-terminal region).
29782851	8	25	theme	cbln1-null	1232:1241	arg1	mice					1243:1246	cbln1-null mice	1232:1246	cbln1-null mice	1232:1246	Cbln4 partially rescued and both glycosylation mutants completely rescued ataxia in cbln1-null mice.
29782851	9	26	theme	function	1367:1374	arg1	gain					1359:1362	gain	1359:1362	gain of function	1359:1374	Thus Cbln4 has intrinsic Grid2 binding that is attenuated by glycosylation, and glycosylation mutants exhibit gain of function in vivo.
29782851	1	27	theme	family	86:91	arg1	Cbln1					58:62	Cbln1	58:62	Cbln1	58:62	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	1	27	theme	family	86:91	arg1	prototype					71:79	the prototype	67:79	the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins	67:131	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	8	28	theme	glycosylation	1181:1193	arg1	mutants					1195:1201	both glycosylation mutants	1176:1201	both glycosylation mutants	1176:1201	Cbln4 partially rescued and both glycosylation mutants completely rescued ataxia in cbln1-null mice.
29782851	0	29	theme	Cblns	17:21	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation of Cblns	0:21	Glycosylation of Cblns attenuates their receptor binding.
29782851	9	30	theme	Grid2	1274:1278	arg1	binding					1280:1286	intrinsic Grid2 binding	1264:1286	intrinsic Grid2 binding that is attenuated by glycosylation	1264:1322	Thus Cbln4 has intrinsic Grid2 binding that is attenuated by glycosylation, and glycosylation mutants exhibit gain of function in vivo.
29782851	3	31	dep	second	484:489	arg1	region					515:520	a region	513:520	a region involved in Grid2 binding	513:546	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	31	dep	second	484:489	arg1	domain					505:510	the C1q domain	497:510	the C1q domain	497:510	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	4	32	theme	C1q	659:661	arg1	site					663:666	the C1q site	655:666	the C1q site	655:666	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	1	33	theme	glycoproteins	119:131	arg1	Cbln1-Cbln4					94:104	Cbln1-Cbln4	94:104	Cbln1-Cbln4	94:104	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	1	33	theme	glycoproteins	119:131	arg1	family					86:91	a family	84:91	a family (Cbln1-Cbln4) of secreted glycoproteins	84:131	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	0	34	theme	receptor	40:47	arg1	binding					49:55	their receptor binding	34:55	their receptor binding	34:55	Glycosylation of Cblns attenuates their receptor binding.
29782851	7	35	theme	glycosylation	1084:1096	arg1	mutants					1098:1104	its glycosylation mutants	1080:1104	its glycosylation mutants	1080:1104	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	0	36	gly	Glycosylation	0:12	arg1	Cblns					17:21	Cblns	17:21	Cblns	17:21	Glycosylation of Cblns attenuates their receptor binding.
29782851	7	37	contain	has	976:978	arg1	Cbln4					970:974	Cbln4	970:974	Cbln4	970:974	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	7	37	contain	has	976:978	arg2	binding					999:1005	undetectable Grid2 binding	980:1005	undetectable Grid2 binding	980:1005	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	5	38	theme	trimeric	764:771	arg1	complexes					773:781	Cbln trimeric complexes	759:781	Cbln trimeric complexes	759:781	These mutations did not influence subunit composition of Cbln trimeric complexes (mediated through the C1q domain) nor their assembly into hexamers (mediated by the N-terminal region).
29782851	4	39	theme	site	602:605	arg1	Mutation					549:556	Mutation	549:556	Mutation (asparagine to glutamine)	549:582	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	4	39	theme	site	602:605	arg1	glutamine					573:581	asparagine to glutamine	559:581	asparagine to glutamine	559:581	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	7	40	theme	type	1066:1069	arg1	expression					1047:1056	transgenic expression	1036:1056	transgenic expression of wild type Cbln4 or its glycosylation mutants	1036:1104	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29782851	4	41	theme	asparagine	559:568	arg1	Mutation					549:556	Mutation	549:556	Mutation (asparagine to glutamine)	549:582	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	4	41	theme	asparagine	559:568	arg1	glutamine					573:581	asparagine to glutamine	559:581	asparagine to glutamine	559:581	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	5	42	theme	C1q	805:807	arg1	domain					809:814	the C1q domain	801:814	the C1q domain	801:814	These mutations did not influence subunit composition of Cbln trimeric complexes (mediated through the C1q domain) nor their assembly into hexamers (mediated by the N-terminal region).
29782851	9	43	theme	intrinsic	1264:1272	arg1	binding					1280:1286	intrinsic Grid2 binding	1264:1286	intrinsic Grid2 binding that is attenuated by glycosylation	1264:1322	Thus Cbln4 has intrinsic Grid2 binding that is attenuated by glycosylation, and glycosylation mutants exhibit gain of function in vivo.
29782851	2	44	theme	receptor	318:325	arg1	properties					335:344	the in vitro receptor binding properties	305:344	the in vitro receptor binding properties of Cblns	305:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	1	45	gly	glycoproteins	119:131	arg1	glycoproteins					119:131	secreted glycoproteins	110:131	secreted glycoproteins	110:131	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	4	46	theme	neurexin	618:625	arg1	binding					627:633	neurexin binding	618:633	neurexin binding	618:633	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	3	47	dep	N-terminus	423:432	arg1	region					442:447	a region	440:447	a region implicated in Nrxn binding	440:474	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	48	from	N-terminus	423:432	arg1	sites					405:409	two N-linked glycosylation sites	378:409	two N-linked glycosylation sites	378:409	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	48	from	N-terminus	423:432	arg1	one					412:414	one	412:414	one	412:414	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	2	49	theme	in	309:310	arg1	properties					335:344	the in vitro receptor binding properties	305:344	the in vitro receptor binding properties of Cblns	305:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	4	50	theme	site	663:666	arg1	mutation					643:650	mutation	643:650	mutation of the C1q site	643:666	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	6	51	theme	binding	938:944	arg1	interfaces					946:955	the receptor binding interfaces	925:955	the receptor binding interfaces of Cblns	925:964	Therefore, glycosylation likely masks the receptor binding interfaces of Cblns.
29782851	9	52	contain	has	1260:1262	arg2	binding					1280:1286	intrinsic Grid2 binding	1264:1286	intrinsic Grid2 binding that is attenuated by glycosylation	1264:1322	Thus Cbln4 has intrinsic Grid2 binding that is attenuated by glycosylation, and glycosylation mutants exhibit gain of function in vivo.
29782851	9	52	contain	has	1260:1262	arg1	Cbln4					1254:1258	Cbln4	1254:1258	Cbln4	1254:1258	Thus Cbln4 has intrinsic Grid2 binding that is attenuated by glycosylation, and glycosylation mutants exhibit gain of function in vivo.
29782851	1	53	theme	secreted	110:117	arg1	glycoproteins					119:131	secreted glycoproteins	110:131	secreted glycoproteins	110:131	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	1	54	theme	bridging	209:216	arg1	Nrxn					230:233	bridging presynaptic Nrxn	209:233	bridging presynaptic Nrxn to postsynaptic Grid2	209:255	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	2	55	gly	glycosylation	288:300	arg1	receptor					318:325	the in vitro receptor binding properties	305:344	the in vitro receptor binding properties of Cblns	305:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	2	55	gly	glycosylation	288:300	arg1	binding					327:333	the in vitro receptor binding properties	305:344	the in vitro receptor binding properties of Cblns	305:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	2	55	gly	glycosylation	288:300	arg1	Cblns					349:353	Cblns	349:353	Cblns	349:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	5	56	theme	complexes	773:781	arg1	composition					744:754	subunit composition	736:754	subunit composition of Cbln trimeric complexes (mediated through the C1q domain)	736:815	These mutations did not influence subunit composition of Cbln trimeric complexes (mediated through the C1q domain) nor their assembly into hexamers (mediated by the N-terminal region).
29782851	3	57	gly	glycosylation	391:403	arg2	two					378:380	two	378:380	two	378:380	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	57	gly	glycosylation	391:403	arg2	second					484:489	second	484:489	second	484:489	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	57	gly	glycosylation	391:403	arg2	one					412:414	one	412:414	one	412:414	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	3	57	gly	glycosylation	391:403	arg2	sites					405:409	two N-linked glycosylation sites	378:409	two N-linked glycosylation sites	378:409	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	2	58	theme	Cblns	349:353	arg1	properties					335:344	the in vitro receptor binding properties	305:344	the in vitro receptor binding properties of Cblns	305:353	Here we report the effects of glycosylation on the in vitro receptor binding properties of Cblns.
29782851	1	59	theme	presynaptic	218:228	arg1	Nrxn					230:233	bridging presynaptic Nrxn	209:233	bridging presynaptic Nrxn to postsynaptic Grid2	209:255	Cbln1 is the prototype of a family (Cbln1-Cbln4) of secreted glycoproteins and is essential for normal synapse structure and function in cerebellum by bridging presynaptic Nrxn to postsynaptic Grid2.
29782851	3	60	theme	Grid2	534:538	arg1	binding					540:546	Grid2 binding	534:546	Grid2 binding	534:546	Cbln1, 2 and 4 harbor two N-linked glycosylation sites, one at the N-terminus is in a region implicated in Nrxn binding and the second is in the C1q domain, a region involved in Grid2 binding.
29782851	4	61	theme	N-terminal	591:600	arg1	site					602:605	the N-terminal site	587:605	the N-terminal site	587:605	Mutation (asparagine to glutamine) of the N-terminal site, increased neurexin binding whereas mutation of the C1q site markedly increased Grid2 binding.
29782851	9	62	theme	glycosylation	1329:1341	arg1	mutants					1343:1349	glycosylation mutants	1329:1349	glycosylation mutants	1329:1349	Thus Cbln4 has intrinsic Grid2 binding that is attenuated by glycosylation, and glycosylation mutants exhibit gain of function in vivo.
29782851	7	63	theme	Cbln1-null	1118:1127	arg1	phenotype					1129:1137	the Cbln1-null phenotype	1114:1137	the Cbln1-null phenotype	1114:1137	As Cbln4 has undetectable Grid2 binding in vitro we assessed whether transgenic expression of wild type Cbln4 or its glycosylation mutants rescued the Cbln1-null phenotype in vivo.
29936833	0	0	from	Functions	16:24	arg1	Brain					59:63	the Brain	55:63	the Brain	55:63	Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics.
29936833	1	1	theme	β-	172:173	arg1	N-acetylglucosamine					175:193	β- N-acetylglucosamine	172:193	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	6	2	theme	different	979:987	arg1	stimuli					989:995	different stimuli	979:995	different stimuli	979:995	Revealing sites that are dynamically altered by different stimuli or disease states will likely go a long way in this regard.
29936833	1	3	gly	glycosylation	195:207	arg2	thousands					241:249	thousands	241:249	thousands of intracellular proteins in the brain	241:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	8	4	theme	site-specific	1277:1289	arg1	O-GlcNAcomics					1321:1333	O-GlcNAcomics	1321:1333	O-GlcNAcomics	1321:1333	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	8	4	theme	site-specific	1277:1289	arg1	proteomics					1309:1318	quantitative, site-specific MS-based O-GlcNAc proteomics	1263:1318	proteomics	1309:1318	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	1	5	theme	N-acetylglucosamine	175:193	arg1	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	5	theme	N-acetylglucosamine	175:193	arg1	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	5	theme	N-acetylglucosamine	175:193	arg1	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	9	6	theme	proteins	1606:1613	arg1	study					1586:1590	the relatively low-throughput study	1556:1590	the relatively low-throughput study of individual proteins	1556:1613	These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins.
29936833	8	7	theme	O-GlcNAc	1300:1307	arg1	O-GlcNAcomics					1321:1333	O-GlcNAcomics	1321:1333	O-GlcNAcomics	1321:1333	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	8	7	theme	O-GlcNAc	1300:1307	arg1	proteomics					1309:1318	quantitative, site-specific MS-based O-GlcNAc proteomics	1263:1318	proteomics	1309:1318	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	0	8	theme	Site-Specific	78:90	arg1	O-GlcNAcomics					105:117	Site-Specific Quantitative O-GlcNAcomics	78:117	Site-Specific Quantitative O-GlcNAcomics	78:117	Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics.
29936833	3	9	from	sites	549:553	arg1	proteins					558:565	proteins	558:565	proteins	558:565	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	7	10	from	sites	1117:1121	arg1	proteins					1137:1144	individual proteins	1126:1144	individual proteins	1126:1144	Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo.
29936833	10	11	theme	neurodegenerative	1908:1924	arg1	functions					1785:1793	the regulatory functions	1770:1793	the regulatory functions of O-GlcNAc in the brain	1770:1818	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	11	theme	neurodegenerative	1908:1924	arg1	diseases					1926:1933	neurodegenerative diseases	1908:1933	neurodegenerative diseases	1908:1933	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	11	theme	neurodegenerative	1908:1924	arg1	roles					1837:1841	their roles	1831:1841	their roles in neuroprotection	1831:1860	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	12	theme	key	1752:1754	arg1	insights					1756:1763	key insights	1752:1763	key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases	1752:1933	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	3	13	theme	individual	538:547	arg1	sites					549:553	individual sites	538:553	individual sites in proteins	538:565	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	9	14	theme	low-throughput	1571:1584	arg1	study					1586:1590	the relatively low-throughput study	1556:1590	the relatively low-throughput study of individual proteins	1556:1613	These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins.
29936833	2	15	theme	functional	362:371	arg1	roles					373:377	important functional roles	352:377	important functional roles	352:377	Like phosphorylation, O-GlcNAcylation is inducible and plays important functional roles in both physiology and disease.
29936833	0	16	theme	O-GlcNAcomics	105:117	arg1	Role					70:73	The Role	66:73	The Role of Site-Specific Quantitative O-GlcNAcomics	66:117	Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics.
29936833	3	17	from	advances	418:425	arg1	MS					449:450	MS	449:450	MS	449:450	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	3	17	from	advances	418:425	arg1	bioconjugation					457:470	bioconjugation	457:470	bioconjugation	457:470	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	3	17	from	advances	418:425	arg1	spectrometry					435:446	mass spectrometry	430:446	mass spectrometry (MS)	430:451	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	3	18	dep	spectrometry	435:446	arg1	methods					472:478	methods	472:478	methods	472:478	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	9	19	theme	O-GlcNAcylated	1528:1541	arg1	proteins					1543:1550	O-GlcNAcylated proteins	1528:1550	O-GlcNAcylated proteins	1528:1550	These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins.
29936833	9	20	theme	proteins	1543:1550	arg1	high-throughput					1497:1511	high-throughput	1497:1511	high-throughput	1497:1511	These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins.
29936833	0	21	theme	Quantitative	92:103	arg1	O-GlcNAcomics					105:117	Site-Specific Quantitative O-GlcNAcomics	78:117	Site-Specific Quantitative O-GlcNAcomics	78:117	Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics.
29936833	5	22	theme	promising	821:829	arg1	sites					831:835	promising sites	821:835	promising sites	821:835	Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed.
29936833	8	23	from	sites	1414:1418	arg1	tracking					1363:1370	proteome-wide tracking	1349:1370	proteome-wide tracking of O-GlcNAcylation dynamics at individual sites	1349:1418	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	5	24	theme	O-GlcNAc	781:788	arg1	sites					790:794	O-GlcNAc sites	781:794	O-GlcNAc sites	781:794	Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed.
29936833	8	25	theme	O-GlcNAcylation	1375:1389	arg1	dynamics					1391:1398	O-GlcNAcylation dynamics	1375:1398	O-GlcNAcylation dynamics	1375:1398	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	7	26	theme	individual	1126:1135	arg1	proteins					1137:1144	individual proteins	1126:1144	individual proteins	1126:1144	Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo.
29936833	10	27	from	roles	1837:1841	arg1	neuroprotection					1846:1860	neuroprotection	1846:1860	neuroprotection	1846:1860	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	2	28	theme	important	352:360	arg1	roles					373:377	important functional roles	352:377	important functional roles	352:377	Like phosphorylation, O-GlcNAcylation is inducible and plays important functional roles in both physiology and disease.
29936833	10	29	theme	regulatory	1774:1783	arg1	functions					1785:1793	the regulatory functions	1770:1793	the regulatory functions of O-GlcNAc in the brain	1770:1818	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	29	theme	regulatory	1774:1783	arg1	learning					1883:1890	learning	1883:1890	learning	1883:1890	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	29	theme	regulatory	1774:1783	arg1	signaling					1872:1880	neuronal signaling	1863:1880	neuronal signaling	1863:1880	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	29	theme	regulatory	1774:1783	arg1	roles					1837:1841	their roles	1831:1841	their roles in neuroprotection	1831:1860	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	29	theme	regulatory	1774:1783	arg1	diseases					1926:1933	neurodegenerative diseases	1908:1933	neurodegenerative diseases	1908:1933	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	3	30	theme	mass	430:433	arg1	MS					449:450	MS	449:450	MS	449:450	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	3	30	theme	mass	430:433	arg1	spectrometry					435:446	mass spectrometry	430:446	mass spectrometry (MS)	430:451	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	6	31	theme	long	1032:1035	arg1	way					1037:1039	a long way	1030:1039	a long way	1030:1039	Revealing sites that are dynamically altered by different stimuli or disease states will likely go a long way in this regard.
29936833	7	32	theme	O-GlcNAc	1108:1115	arg1	sites					1117:1121	O-GlcNAc sites	1108:1121	O-GlcNAc sites on individual proteins and across the proteome	1108:1168	Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo.
29936833	1	33	attach	present	230:236	arg2	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	33	attach	present	230:236	arg2	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	33	attach	present	230:236	arg2	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	33	attach	present	230:236	arg1	thousands					241:249	thousands	241:249	thousands of intracellular proteins in the brain	241:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	3	34	theme	Recent	411:416	arg1	advances					418:425	Recent advances	411:425	Recent advances in mass spectrometry (MS) and bioconjugation methods	411:478	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	4	35	theme	understanding	581:593	arg1	necessary					629:637	necessary	629:637	necessary	629:637	However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy.
29936833	4	36	theme	specific	687:694	arg1	processes					696:704	specific processes	687:704	specific processes	687:704	However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy.
29936833	4	37	theme	glycosylation	604:616	arg1	events					618:623	glycosylation events	604:623	glycosylation events	604:623	However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy.
29936833	10	38	theme	neuronal	1863:1870	arg1	functions					1785:1793	the regulatory functions	1770:1793	the regulatory functions of O-GlcNAc in the brain	1770:1818	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	38	theme	neuronal	1863:1870	arg1	signaling					1872:1880	neuronal signaling	1863:1880	neuronal signaling	1863:1880	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	38	theme	neuronal	1863:1870	arg1	roles					1837:1841	their roles	1831:1841	their roles in neuroprotection	1831:1860	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	6	39	theme	Revealing	931:939	arg1	sites					941:945	Revealing sites	931:945	Revealing sites that are dynamically altered by different stimuli or disease states	931:1013	Revealing sites that are dynamically altered by different stimuli or disease states will likely go a long way in this regard.
29936833	8	40	theme	individual	1403:1412	arg1	sites					1414:1418	individual sites	1403:1418	individual sites	1403:1418	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	5	41	theme	functional	892:901	arg1	studies					903:909	resource-intensive functional studies	873:909	resource-intensive functional studies	873:909	Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed.
29936833	0	42	theme	Glycosylation	38:50	arg1	Functions					16:24	the Functions	12:24	the Functions of O-GlcNAc Glycosylation in the Brain	12:63	Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics.
29936833	5	43	theme	sheer	765:769	arg1	number					771:776	the sheer number	761:776	the sheer number of O-GlcNAc sites	761:794	Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed.
29936833	9	44	theme	cutting-edge	1427:1438	arg1	technologies					1440:1451	These cutting-edge technologies	1421:1451	These cutting-edge technologies	1421:1451	These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins.
29936833	0	45	theme	O-GlcNAc	29:36	arg1	Glycosylation					38:50	O-GlcNAc Glycosylation	29:50	O-GlcNAc Glycosylation	29:50	Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics.
29936833	1	46	from	brain	284:288	arg1	thousands					241:249	thousands	241:249	thousands of intracellular proteins in the brain	241:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	8	47	theme	dynamics	1391:1398	arg1	tracking					1363:1370	proteome-wide tracking	1349:1370	proteome-wide tracking of O-GlcNAcylation dynamics at individual sites	1349:1418	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	10	48	theme	new	1723:1725	arg1	approaches					1727:1736	these new approaches	1717:1736	these new approaches	1717:1736	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	5	49	theme	sites	790:794	arg1	number					771:776	the sheer number	761:776	the sheer number of O-GlcNAc sites	761:794	Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed.
29936833	8	50	theme	MS-based	1291:1298	arg1	O-GlcNAcomics					1321:1333	O-GlcNAcomics	1321:1333	O-GlcNAcomics	1321:1333	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	8	50	theme	MS-based	1291:1298	arg1	proteomics					1309:1318	quantitative, site-specific MS-based O-GlcNAc proteomics	1263:1318	proteomics	1309:1318	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	1	51	from	proteins	268:275	arg1	brain					284:288	the brain	280:288	the brain	280:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	52	from	thousands	241:249	arg1	brain					284:288	the brain	280:288	the brain	280:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	3	53	theme	events	528:533	arg1	mapping					501:507	the mapping	497:507	the mapping of O-GlcNAcylation events to individual sites in proteins	497:565	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	1	54	link	O-linked	163:170	arg1	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	54	link	O-linked	163:170	arg1	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	54	link	O-linked	163:170	arg1	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	6	55	theme	disease	1000:1006	arg1	states					1008:1013	disease states	1000:1013	disease states	1000:1013	Revealing sites that are dynamically altered by different stimuli or disease states will likely go a long way in this regard.
29936833	1	56	located	present	230:236	arg2	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	56	located	present	230:236	arg2	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	56	located	present	230:236	arg2	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	56	located	present	230:236	arg1	thousands					241:249	thousands	241:249	thousands of intracellular proteins in the brain	241:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	8	57	theme	quantitative	1263:1274	arg1	O-GlcNAcomics					1321:1333	O-GlcNAcomics	1321:1333	O-GlcNAcomics	1321:1333	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	8	57	theme	quantitative	1263:1274	arg1	proteomics					1309:1318	quantitative, site-specific MS-based O-GlcNAc proteomics	1263:1318	proteomics	1309:1318	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	8	58	theme	proteome-wide	1349:1361	arg1	tracking					1363:1370	proteome-wide tracking	1349:1370	proteome-wide tracking of O-GlcNAcylation dynamics at individual sites	1349:1418	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	8	59	theme	emerging	1237:1244	arg1	technologies					1246:1257	emerging technologies	1237:1257	emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites	1237:1418	We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites.
29936833	10	60	theme	O-GlcNAcylation	1634:1648	arg1	events					1650:1655	the O-GlcNAcylation events	1630:1655	the O-GlcNAcylation events that change in specific physiological and disease contexts	1630:1714	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	61	from	functions	1785:1793	arg1	brain					1814:1818	the brain	1810:1818	the brain	1810:1818	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	1	62	theme	dynamic	124:130	arg1	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	62	theme	dynamic	124:130	arg1	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	62	theme	dynamic	124:130	arg1	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	10	63	theme	disease	1699:1705	arg1	contexts					1707:1714	specific physiological and disease contexts	1672:1714	contexts	1707:1714	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	4	64	theme	protein	654:660	arg1	function					662:669	protein function	654:669	protein function	654:669	However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy.
29936833	7	65	theme	advanced	1075:1082	arg1	methods					1084:1090	advanced methods	1075:1090	advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo	1075:1216	Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo.
29936833	10	66	theme	O-GlcNAc	1798:1805	arg1	functions					1785:1793	the regulatory functions	1770:1793	the regulatory functions of O-GlcNAc in the brain	1770:1818	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	66	theme	O-GlcNAc	1798:1805	arg1	learning					1883:1890	learning	1883:1890	learning	1883:1890	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	66	theme	O-GlcNAc	1798:1805	arg1	signaling					1872:1880	neuronal signaling	1863:1880	neuronal signaling	1863:1880	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	66	theme	O-GlcNAc	1798:1805	arg1	roles					1837:1841	their roles	1831:1841	their roles in neuroprotection	1831:1860	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	10	66	theme	O-GlcNAc	1798:1805	arg1	diseases					1926:1933	neurodegenerative diseases	1908:1933	neurodegenerative diseases	1908:1933	By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.
29936833	1	67	theme	posttranslational	132:148	arg1	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	67	theme	posttranslational	132:148	arg1	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	67	theme	posttranslational	132:148	arg1	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	68	theme	intracellular	254:266	arg1	proteins					268:275	intracellular proteins	254:275	intracellular proteins in the brain	254:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	9	69	theme	individual	1595:1604	arg1	proteins					1606:1613	individual proteins	1595:1613	individual proteins	1595:1613	These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloguing of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins.
29936833	5	70	theme	resource-intensive	873:890	arg1	studies					903:909	resource-intensive functional studies	873:909	resource-intensive functional studies	873:909	Given the sheer number of O-GlcNAc sites, methods for identifying promising sites and prioritizing them for time- and resource-intensive functional studies are greatly needed.
29936833	1	71	theme	modification	150:161	arg1	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	71	theme	modification	150:161	arg1	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	71	theme	modification	150:161	arg1	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	3	72	theme	O-GlcNAcylation	512:526	arg1	events					528:533	O-GlcNAcylation events	512:533	O-GlcNAcylation events	512:533	Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins.
29936833	1	73	theme	proteins	268:275	arg1	thousands					241:249	thousands	241:249	thousands of intracellular proteins in the brain	241:288	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	7	74	dep	methods	1084:1090	arg1	determining					1178:1188	determining	1178:1188	determining their stoichiometry in vivo	1178:1216	Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo.
29936833	7	74	dep	methods	1084:1090	arg1	identifying					1096:1106	identifying	1096:1106	identifying O-GlcNAc sites on individual proteins and across the proteome	1096:1168	Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome and for determining their stoichiometry in vivo.
29936833	0	75	dep	Deciphering	0:10	arg1	Role					70:73	The Role	66:73	The Role of Site-Specific Quantitative O-GlcNAcomics	66:117	Deciphering the Functions of O-GlcNAc Glycosylation in the Brain: The Role of Site-Specific Quantitative O-GlcNAcomics.
29936833	1	76	theme	O-linked	163:170	arg1	O-GlcNAcylation					210:224	O-GlcNAcylation	210:224	O-GlcNAcylation	210:224	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	76	theme	O-linked	163:170	arg1	present					230:236	present	230:236	present	230:236	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29936833	1	76	theme	O-linked	163:170	arg1	glycosylation					195:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation	120:207	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation)	120:225	The dynamic posttranslational modification O-linked β- N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain.
29513221	0	0	theme	cytoskeleton	89:100	arg1	function					51:58	function	51:58	function	51:58	Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.
29513221	0	0	theme	cytoskeleton	89:100	arg1	form					42:45	form	42:45	form	42:45	Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.
29513221	0	1	theme	filament	80:87	arg1	cytoskeleton					89:100	the intermediate filament cytoskeleton	63:100	the intermediate filament cytoskeleton	63:100	Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.
29513221	2	2	theme	skin	333:336	arg1	disorders					338:346	skin disorders	333:346	skin disorders	333:346	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	1	3	theme	signal	242:247	arg1	transduction					249:260	signal transduction	242:260	signal transduction	242:260	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	6	4	theme	regulation	1204:1213	arg1	understanding					1183:1195	our understanding	1179:1195	our understanding of the regulation of IF proteins in general	1179:1239	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	4	5	with	modification	560:571	arg1	O-GlcNAc					650:657	O-GlcNAc	650:657	O-GlcNAc	650:657	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	4	5	with	modification	560:571	arg1	β-N-acetylglucosamine					627:647	O-linked β-N-acetylglucosamine	618:647	O-linked β-N-acetylglucosamine (O-GlcNAc)	618:658	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	4	6	theme	IF	593:594	arg1	vimentin					604:611	the prototypical IF protein vimentin	576:611	the prototypical IF protein vimentin	576:611	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	6	7	theme	IF	1218:1219	arg1	proteins					1221:1228	IF proteins	1218:1228	IF proteins	1218:1228	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	2	8	theme	IFs	280:282	arg1	Dysregulation					263:275	Dysregulation	263:275	Dysregulation of IFs	263:282	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	4	9	theme	prototypical	580:591	arg1	vimentin					604:611	the prototypical IF protein vimentin	576:611	the prototypical IF protein vimentin	576:611	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	5	10	theme	specific	924:931	arg1	sites					956:960	specific vimentin glycosylation sites	924:960	specific vimentin glycosylation sites	924:960	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	4	11	theme	protein-protein	683:697	arg1	interactions					699:710	its homotypic protein-protein interactions	669:710	its homotypic protein-protein interactions	669:710	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	1	12	theme	metazoan	160:167	arg1	cytoskeleton					169:180	the metazoan cytoskeleton	156:180	the metazoan cytoskeleton	156:180	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	6	13	theme	broad	1156:1160	arg1	implications					1162:1173	broad implications	1156:1173	broad implications for our understanding of the regulation of IF proteins in general	1156:1239	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	5	14	theme	intracellular	811:823	arg1	trachomatis					844:854	the intracellular pathogen Chlamydia trachomatis	807:854	the intracellular pathogen Chlamydia trachomatis	807:854	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	1	15	theme	cytoskeleton	169:180	arg1	component					143:151	a major component	135:151	a major component of the metazoan cytoskeleton	135:180	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	1	15	theme	cytoskeleton	169:180	arg1	filaments					116:124	Intermediate filaments	103:124	Intermediate filaments (IF)	103:129	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	3	16	theme	pathophysiological	411:428	arg1	significance					430:441	this pathophysiological significance	406:441	this pathophysiological significance	406:441	Despite this pathophysiological significance, how cells regulate IF structure, dynamics, and function remains poorly understood.
29513221	0	17	theme	Site-specific	0:12	arg1	glycosylation					14:26	Site-specific glycosylation	0:26	Site-specific glycosylation	0:26	Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.
29513221	1	18	theme	Intermediate	103:114	arg1	component					143:151	a major component	135:151	a major component of the metazoan cytoskeleton	135:180	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	1	18	theme	Intermediate	103:114	arg1	filaments					116:124	Intermediate filaments	103:124	Intermediate filaments (IF)	103:129	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	6	19	from	understanding	1183:1195	arg1	general					1233:1239	general	1233:1239	general	1233:1239	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	4	20	theme	homotypic	673:681	arg1	interactions					699:710	its homotypic protein-protein interactions	669:710	its homotypic protein-protein interactions	669:710	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	5	21	theme	pathogen	825:832	arg1	trachomatis					844:854	the intracellular pathogen Chlamydia trachomatis	807:854	the intracellular pathogen Chlamydia trachomatis	807:854	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	4	22	theme	cell	765:768	arg1	migration					770:778	cell migration	765:778	cell migration	765:778	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	5	23	theme	Chlamydia	834:842	arg1	trachomatis					844:854	the intracellular pathogen Chlamydia trachomatis	807:854	the intracellular pathogen Chlamydia trachomatis	807:854	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	5	24	theme	O-GlcNAc	966:973	arg1	transferase					975:985	O-GlcNAc transferase	966:985	O-GlcNAc transferase activity	966:994	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	4	25	link	O-linked	618:625	arg1	O-GlcNAc					650:657	O-GlcNAc	650:657	O-GlcNAc	650:657	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	4	25	link	O-linked	618:625	arg1	β-N-acetylglucosamine					627:647	O-linked β-N-acetylglucosamine	618:647	O-linked β-N-acetylglucosamine (O-GlcNAc)	618:658	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	6	26	theme	O-GlcNAcylation	1126:1140	arg1	functions					1104:1112	the biochemical and cell biological functions	1068:1112	the biochemical and cell biological functions of vimentin O-GlcNAcylation	1068:1140	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	4	27	theme	site-specific	546:558	arg1	modification					560:571	site-specific modification	546:571	site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc)	546:658	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	6	28	theme	biochemical	1072:1082	arg1	functions					1104:1112	the biochemical and cell biological functions	1068:1112	the biochemical and cell biological functions of vimentin O-GlcNAcylation	1068:1140	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	6	29	theme	biological	1093:1102	arg1	functions					1104:1112	the biochemical and cell biological functions	1068:1112	the biochemical and cell biological functions of vimentin O-GlcNAcylation	1068:1140	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	1	30	theme	normal	204:209	arg1	morphology					216:225	normal cell morphology	204:225	normal cell morphology	204:225	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	6	31	theme	vimentin	1117:1124	arg1	O-GlcNAcylation					1126:1140	vimentin O-GlcNAcylation	1117:1140	vimentin O-GlcNAcylation	1117:1140	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	5	32	gly	glycosylation	942:954	arg2	sites					956:960	specific vimentin glycosylation sites	924:960	specific vimentin glycosylation sites	924:960	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	6	33	theme	new	1051:1053	arg1	insight					1055:1061	new insight	1051:1061	new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation	1051:1140	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	1	34	theme	cell	211:214	arg1	morphology					216:225	normal cell morphology	204:225	normal cell morphology	204:225	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	6	35	from	regulation	1204:1213	arg1	general					1233:1239	general	1233:1239	general	1233:1239	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	4	36	theme	human	731:735	arg1	cells					737:741	human cells	731:741	human cells	731:741	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	5	37	theme	transferase	975:985	arg1	activity					987:994	O-GlcNAc transferase activity	966:994	O-GlcNAc transferase activity	966:994	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	0	38	dep	form	42:45	arg1	the					38:40	the	38:40	the	38:40	Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.
29513221	5	39	theme	vimentin	933:940	arg1	sites					956:960	specific vimentin glycosylation sites	924:960	specific vimentin glycosylation sites	924:960	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	2	40	theme	diseases	313:320	arg1	disorders					338:346	skin disorders	333:346	skin disorders	333:346	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	40	theme	diseases	313:320	arg1	range					298:302	a wide range	291:302	a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy	291:395	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	40	theme	diseases	313:320	arg1	lipodystrophy					367:379	lipodystrophy	367:379	lipodystrophy	367:379	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	40	theme	diseases	313:320	arg1	neuropathy					386:395	neuropathy	386:395	neuropathy	386:395	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	40	theme	diseases	313:320	arg1	cardiomyopathies					349:364	cardiomyopathies	349:364	cardiomyopathies	349:364	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	41	theme	wide	293:296	arg1	disorders					338:346	skin disorders	333:346	skin disorders	333:346	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	41	theme	wide	293:296	arg1	range					298:302	a wide range	291:302	a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy	291:395	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	41	theme	wide	293:296	arg1	lipodystrophy					367:379	lipodystrophy	367:379	lipodystrophy	367:379	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	41	theme	wide	293:296	arg1	neuropathy					386:395	neuropathy	386:395	neuropathy	386:395	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	41	theme	wide	293:296	arg1	cardiomyopathies					349:364	cardiomyopathies	349:364	cardiomyopathies	349:364	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	4	42	theme	vimentin	604:611	arg1	modification					560:571	site-specific modification	546:571	site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc)	546:658	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	5	43	theme	glycosylation	942:954	arg1	sites					956:960	specific vimentin glycosylation sites	924:960	specific vimentin glycosylation sites	924:960	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	6	44	contain	have	1151:1154	arg2	implications					1162:1173	broad implications	1156:1173	broad implications for our understanding of the regulation of IF proteins in general	1156:1239	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	6	44	contain	have	1151:1154	arg1	results					1035:1041	Our results	1031:1041	Our results	1031:1041	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	6	45	theme	proteins	1221:1228	arg1	regulation					1204:1213	the regulation	1200:1213	the regulation of IF proteins in general	1200:1239	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
29513221	2	46	theme	human	307:311	arg1	lipodystrophy					367:379	lipodystrophy	367:379	lipodystrophy	367:379	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	46	theme	human	307:311	arg1	disorders					338:346	skin disorders	333:346	skin disorders	333:346	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	46	theme	human	307:311	arg1	diseases					313:320	human diseases	307:320	human diseases	307:320	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	46	theme	human	307:311	arg1	neuropathy					386:395	neuropathy	386:395	neuropathy	386:395	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	2	46	theme	human	307:311	arg1	cardiomyopathies					349:364	cardiomyopathies	349:364	cardiomyopathies	349:364	Dysregulation of IFs causes a wide range of human diseases, including skin disorders, cardiomyopathies, lipodystrophy, and neuropathy.
29513221	4	47	theme	protein	596:602	arg1	vimentin					604:611	the prototypical IF protein vimentin	576:611	the prototypical IF protein vimentin	576:611	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	0	48	theme	intermediate	67:78	arg1	cytoskeleton					89:100	the intermediate filament cytoskeleton	63:100	the intermediate filament cytoskeleton	63:100	Site-specific glycosylation regulates the form and function of the intermediate filament cytoskeleton.
29513221	1	49	theme	major	137:141	arg1	component					143:151	a major component	135:151	a major component of the metazoan cytoskeleton	135:180	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	1	49	theme	major	137:141	arg1	filaments					116:124	Intermediate filaments	103:124	Intermediate filaments (IF)	103:129	Intermediate filaments (IF) are a major component of the metazoan cytoskeleton and are essential for normal cell morphology, motility, and signal transduction.
29513221	4	50	theme	O-linked	618:625	arg1	O-GlcNAc					650:657	O-GlcNAc	650:657	O-GlcNAc	650:657	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	4	50	theme	O-linked	618:625	arg1	β-N-acetylglucosamine					627:647	O-linked β-N-acetylglucosamine	618:647	O-linked β-N-acetylglucosamine (O-GlcNAc)	618:658	Here, we show that site-specific modification of the prototypical IF protein vimentin with O-linked β-N-acetylglucosamine (O-GlcNAc) mediates its homotypic protein-protein interactions and is required in human cells for IF morphology and cell migration.
29513221	5	51	theme	replicative	1012:1022	arg1	niche					1024:1028	its replicative niche	1008:1028	its replicative niche	1008:1028	In addition, we show that the intracellular pathogen Chlamydia trachomatis, which remodels the host IF cytoskeleton during infection, requires specific vimentin glycosylation sites and O-GlcNAc transferase activity to maintain its replicative niche.
29513221	6	52	from	general	1233:1239	arg1	understanding					1183:1195	our understanding	1179:1195	our understanding of the regulation of IF proteins in general	1179:1239	Our results provide new insight into the biochemical and cell biological functions of vimentin O-GlcNAcylation, and may have broad implications for our understanding of the regulation of IF proteins in general.
27690717	1	0	theme	subunit	296:302	arg1	Slo					230:232	Slo	230:232	Slo	230:232	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	1	0	theme	subunit	296:302	arg1	subunit					221:227	a pore-forming α subunit	204:227	a pore-forming α subunit (Slo)	204:233	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	1	0	theme	subunit	296:302	arg1	types					241:245	4 types	239:245	4 types of auxiliary β subunits or just a pore-forming α subunit	239:302	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	2	1	theme	N-linked	323:330	arg1	sites					346:350	multiple N-linked glycosylation sites	314:350	multiple N-linked glycosylation sites in the extracellular loop of β subunits	314:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	6	2	gly	N-glycosylation	1230:1244	arg1	subunits					1252:1259	β2 subunits	1249:1259	β2 subunits	1249:1259	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	6	2	gly	N-glycosylation	1230:1244	arg1	phenotypes					1383:1392	the pathological phenotypes	1366:1392	the pathological phenotypes of carbohydrate metabolic diseases	1366:1427	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	0	3	theme	functional	71:80	arg1	phenotypes					82:91	functional phenotypes	71:91	functional phenotypes of BK Channels	71:106	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	5	4	theme	extracellular	1074:1086	arg1	cavum					1088:1092	the extracellular cavum	1070:1092	the extracellular cavum above the pore of the channel	1070:1122	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	3	5	from	N119	717:720	arg1	sites					627:631	3 sites	625:631	3 sites in the extracellular loop of β2 subunit	625:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	5	from	N119	717:720	arg1	N-X-T/S					693:699	N-X-T/S	693:699	N-X-T/S	693:699	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	2	6	theme	multiple	314:321	arg1	sites					346:350	multiple N-linked glycosylation sites	314:350	multiple N-linked glycosylation sites in the extracellular loop of β subunits	314:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	0	7	theme	BK	96:97	arg1	Channels					99:106	BK Channels	96:106	BK Channels	96:106	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	5	8	theme	cavum	1088:1092	arg1	dimension					1057:1065	the dimension	1053:1065	the dimension of the extracellular cavum above the pore of the channel	1053:1122	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	6	9	gly	heterogeneity	1305:1317	arg1	channels					1325:1332	BK channels	1322:1332	BK channels	1322:1332	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	6	10	theme	diseases	1420:1427	arg1	phenotypes					1383:1392	the pathological phenotypes	1366:1392	the pathological phenotypes of carbohydrate metabolic diseases	1366:1427	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	5	11	theme	biophysical	1146:1156	arg1	properties					1178:1187	biophysical and pharmacological properties	1146:1187	biophysical and pharmacological properties of BK channels	1146:1202	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	6	12	theme	BK	1322:1323	arg1	channels					1325:1332	BK channels	1322:1332	BK channels	1322:1332	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	2	13	link	N-linked	323:330	arg1	sites					346:350	multiple N-linked glycosylation sites	314:350	multiple N-linked glycosylation sites in the extracellular loop of β subunits	314:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	4	14	theme	toxin	830:834	arg1	sensitivity					836:846	toxin sensitivity	830:846	toxin sensitivity	830:846	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	5	15	theme	molecular	936:944	arg1	MD					956:957	MD	956:957	MD	956:957	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	5	15	theme	molecular	936:944	arg1	dynamics					946:953	molecular dynamics	936:953	molecular dynamics (MD)	936:958	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	4	16	theme	sites	747:751	arg1	Glycosylation					724:736	Glycosylation	724:736	Glycosylation of these sites	724:751	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	6	17	theme	functional	1294:1303	arg1	heterogeneity					1305:1317	functional heterogeneity	1294:1317	functional heterogeneity of BK channels	1294:1332	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	5	18	theme	subunits	1030:1037	arg1	association					1010:1020	the association	1006:1020	the association of α/β2 subunits	1006:1037	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	0	19	theme	Channels	99:106	arg1	phenotypes					82:91	functional phenotypes	71:91	functional phenotypes of BK Channels	71:106	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	6	20	theme	channels	1325:1332	arg1	heterogeneity					1305:1317	functional heterogeneity	1294:1317	functional heterogeneity of BK channels	1294:1332	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	3	21	from	N88	704:706	arg1	sites					627:631	3 sites	625:631	3 sites in the extracellular loop of β2 subunit	625:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	21	from	N88	704:706	arg1	N-X-T/S					693:699	N-X-T/S	693:699	N-X-T/S	693:699	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	6	22	theme	carbohydrate	1397:1408	arg1	diseases					1420:1427	carbohydrate metabolic diseases	1397:1427	carbohydrate metabolic diseases	1397:1427	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	6	23	theme	pathological	1370:1381	arg1	phenotypes					1383:1392	the pathological phenotypes	1366:1392	the pathological phenotypes of carbohydrate metabolic diseases	1366:1427	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	2	24	theme	extracellular	359:371	arg1	loop					373:376	the extracellular loop	355:376	the extracellular loop of β subunits	355:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	6	25	theme	metabolic	1410:1418	arg1	diseases					1420:1427	carbohydrate metabolic diseases	1397:1427	carbohydrate metabolic diseases	1397:1427	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	4	26	theme	outward	807:813	arg1	rectification					815:827	outward rectification	807:827	outward rectification	807:827	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	4	27	theme	β2	891:892	arg1	subunits					894:901	the α and β2 subunits	881:901	subunits	894:901	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	3	28	from	N96	709:711	arg1	sites					627:631	3 sites	625:631	3 sites in the extracellular loop of β2 subunit	625:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	28	from	N96	709:711	arg1	N-X-T/S					693:699	N-X-T/S	693:699	N-X-T/S	693:699	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	2	29	from	sites	346:350	arg1	loop					373:376	the extracellular loop	355:376	the extracellular loop of β subunits	355:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	3	30	theme	site-directed	536:548	arg1	mutagenesis					550:560	site-directed mutagenesis	536:560	site-directed mutagenesis	536:560	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	1	31	theme	auxiliary	250:258	arg1	subunits					262:269	auxiliary β subunits	250:269	auxiliary β subunits	250:269	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	2	32	gly	glycosylation	332:344	arg2	sites					346:350	multiple N-linked glycosylation sites	314:350	multiple N-linked glycosylation sites in the extracellular loop of β subunits	314:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	1	33	dep	potassium	155:163	arg1	BK					175:176	BK	175:176	BK	175:176	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	1	33	dep	potassium	155:163	arg1	MaxiK					166:170	MaxiK	166:170	MaxiK	166:170	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	5	34	used	used	931:934	arg2	We					904:905	We	904:905	We	904:905	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	1	35	theme	β	260:260	arg1	subunits					262:269	auxiliary β subunits	250:269	auxiliary β subunits	250:269	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	2	36	dep	structure	474:482	arg1	the					470:472	the	470:472	the	470:472	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	2	37	theme	subunits	383:390	arg1	loop					373:376	the extracellular loop	355:376	the extracellular loop of β subunits	355:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	0	38	theme	loop	39:42	arg1	glycosylation					4:16	The glycosylation	0:16	The glycosylation of the extracellular loop of β2 subunits	0:57	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	1	39	theme	subunits	262:269	arg1	Slo					230:232	Slo	230:232	Slo	230:232	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	1	39	theme	subunits	262:269	arg1	subunit					221:227	a pore-forming α subunit	204:227	a pore-forming α subunit (Slo)	204:233	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	1	39	theme	subunits	262:269	arg1	types					241:245	4 types	239:245	4 types of auxiliary β subunits or just a pore-forming α subunit	239:302	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	2	40	theme	channels	503:510	arg1	function					488:495	function	488:495	function	488:495	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	2	40	theme	channels	503:510	arg1	structure					474:482	structure	474:482	structure	474:482	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	5	41	theme	pharmacological	1162:1176	arg1	properties					1178:1187	biophysical and pharmacological properties	1146:1187	biophysical and pharmacological properties of BK channels	1146:1202	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	3	42	theme	western	563:569	arg1	blot					571:574	western blot	563:574	western blot	563:574	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	2	43	theme	β	381:381	arg1	subunits					383:390	β subunits	381:390	β subunits	381:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	0	44	theme	extracellular	25:37	arg1	loop					39:42	the extracellular loop	21:42	the extracellular loop of β2 subunits	21:57	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	2	45	theme	BK	500:501	arg1	channels					503:510	BK channels	500:510	BK channels	500:510	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	5	46	theme	α/β2	1025:1028	arg1	subunits					1030:1037	α/β2 subunits	1025:1037	α/β2 subunits	1025:1037	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	0	47	gly	glycosylation	4:16	arg1	loop					39:42	the extracellular loop	21:42	the extracellular loop of β2 subunits	21:57	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	1	48	theme	pore-forming	206:217	arg1	Slo					230:232	Slo	230:232	Slo	230:232	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	1	48	theme	pore-forming	206:217	arg1	subunit					221:227	a pore-forming α subunit	204:227	a pore-forming α subunit (Slo)	204:233	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	0	49	theme	β2	47:48	arg1	subunits					50:57	β2 subunits	47:57	β2 subunits	47:57	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	3	50	dep	N-glycosylated	677:690	arg1	sites					627:631	3 sites	625:631	3 sites in the extracellular loop of β2 subunit	625:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	50	dep	N-glycosylated	677:690	arg1	N-X-T/S					693:699	N-X-T/S	693:699	N-X-T/S	693:699	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	4	51	theme	physical	852:859	arg1	association					861:871	physical association	852:871	physical association between the α and β2 subunits	852:901	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	5	52	theme	channel	1116:1122	arg1	pore					1104:1107	the pore	1100:1107	the pore of the channel	1100:1122	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	3	53	theme	mutagenesis	550:560	arg1	combination					521:531	a combination	519:531	a combination of site-directed mutagenesis, western blot and patch-clamp recordings	519:601	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	1	54	theme	Large-conductance	109:125	arg1	Ca2+-					127:131	Large-conductance Ca2+-	109:131	Large-conductance Ca2+-	109:131	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	6	55	theme	crucial	1267:1273	arg1	roles					1275:1279	crucial roles	1267:1279	crucial roles	1267:1279	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	3	56	theme	β2	662:663	arg1	subunit					665:671	β2 subunit	662:671	β2 subunit	662:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	4	57	theme	gating	790:795	arg1	kinetics					797:804	gating kinetics	790:804	gating kinetics	790:804	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	1	58	theme	pore-forming	281:292	arg1	subunit					296:302	just a pore-forming α subunit	274:302	just a pore-forming α subunit	274:302	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	6	59	theme	subunits	1252:1259	arg1	N-glycosylation					1230:1244	N-glycosylation	1230:1244	N-glycosylation of β2 subunits	1230:1259	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	3	60	theme	extracellular	640:652	arg1	loop					654:657	the extracellular loop	636:657	the extracellular loop of β2 subunit	636:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	61	theme	recordings	592:601	arg1	combination					521:531	a combination	519:531	a combination of site-directed mutagenesis, western blot and patch-clamp recordings	519:601	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	62	theme	blot	571:574	arg1	combination					521:531	a combination	519:531	a combination of site-directed mutagenesis, western blot and patch-clamp recordings	519:601	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	1	63	theme	α	219:219	arg1	Slo					230:232	Slo	230:232	Slo	230:232	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	1	63	theme	α	219:219	arg1	subunit					221:227	a pore-forming α subunit	204:227	a pore-forming α subunit (Slo)	204:233	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	6	64	theme	β2	1249:1250	arg1	subunits					1252:1259	β2 subunits	1249:1259	β2 subunits	1249:1259	Our results suggest that N-glycosylation of β2 subunits plays crucial roles in imparting functional heterogeneity of BK channels, and is potentially involved in the pathological phenotypes of carbohydrate metabolic diseases.
27690717	1	65	theme	voltage-activated	137:153	arg1	potassium					155:163	voltage-activated potassium	137:163	voltage-activated potassium (MaxiK or BK) channels	137:186	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	3	66	from	sites	627:631	arg1	loop					654:657	the extracellular loop	636:657	the extracellular loop of β2 subunit	636:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	4	67	theme	α	885:885	arg1	subunits					894:901	the α and β2 subunits	881:901	subunits	894:901	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	3	68	gly	N-glycosylated	677:690	arg1	sites					627:631	3 sites	625:631	3 sites in the extracellular loop of β2 subunit	625:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	68	gly	N-glycosylated	677:690	arg1	N-X-T/S					693:699	N-X-T/S	693:699	N-X-T/S	693:699	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	1	69	theme	potassium	155:163	arg1	channels					179:186	voltage-activated potassium (MaxiK or BK) channels	137:186	voltage-activated potassium (MaxiK or BK) channels	137:186	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	4	70	gly	Glycosylation	724:736	arg1	sites					747:751	these sites	741:751	these sites	741:751	Glycosylation of these sites strongly and differentially regulate gating kinetics, outward rectification, toxin sensitivity and physical association between the α and β2 subunits.
27690717	0	71	theme	subunits	50:57	arg1	loop					39:42	the extracellular loop	21:42	the extracellular loop of β2 subunits	21:57	The glycosylation of the extracellular loop of β2 subunits diversifies functional phenotypes of BK Channels.
27690717	1	72	theme	α	294:294	arg1	subunit					296:302	just a pore-forming α subunit	274:302	just a pore-forming α subunit	274:302	Large-conductance Ca2+- and voltage-activated potassium (MaxiK or BK) channels are composed of a pore-forming α subunit (Slo) and 4 types of auxiliary β subunits or just a pore-forming α subunit.
27690717	3	73	theme	patch-clamp	580:590	arg1	recordings					592:601	patch-clamp recordings	580:601	patch-clamp recordings	580:601	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	3	74	theme	subunit	665:671	arg1	loop					654:657	the extracellular loop	636:657	the extracellular loop of β2 subunit	636:671	Using a combination of site-directed mutagenesis, western blot and patch-clamp recordings, we demonstrated that 3 sites in the extracellular loop of β2 subunit are N-glycosylated (N-X-T/S at N88, N96 and N119).
27690717	2	75	theme	glycosylation	332:344	arg1	sites					346:350	multiple N-linked glycosylation sites	314:350	multiple N-linked glycosylation sites in the extracellular loop of β subunits	314:390	Although multiple N-linked glycosylation sites in the extracellular loop of β subunits have been identified, very little is known about how glycosylation influences the structure and function of BK channels.
27690717	5	76	theme	channels	1195:1202	arg1	properties					1178:1187	biophysical and pharmacological properties	1146:1187	biophysical and pharmacological properties of BK channels	1146:1202	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
27690717	5	77	theme	BK	1192:1193	arg1	channels					1195:1202	BK channels	1192:1202	BK channels	1192:1202	We constructed a model and used molecular dynamics (MD) to simulate how the glycosylation facilitates the association of α/β2 subunits and modulates the dimension of the extracellular cavum above the pore of the channel, ultimately to modify biophysical and pharmacological properties of BK channels.
30135544	9	0	theme	PrP	1593:1595	arg1	aggregation					1572:1582	the aggregation	1568:1582	the aggregation of human PrP	1568:1595	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	9	0	theme	PrP	1593:1595	arg1	cofactor					1469:1476	a necessary cofactor	1457:1476	a necessary cofactor	1457:1476	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	9	0	theme	PrP	1593:1595	arg1	glycosylation					1435:1447	glycosylation	1435:1447	glycosylation	1435:1447	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	9	0	theme	PrP	1593:1595	arg1	cytotoxicity					1615:1626	its cytotoxicity	1611:1626	its cytotoxicity	1611:1626	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	3	1	theme	PrP	455:457	arg1	toxicity					437:444	toxicity	437:444	toxicity	437:444	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	3	1	theme	PrP	455:457	arg1	aggregation					421:431	aggregation	421:431	aggregation	421:431	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	7	2	from	located	1084:1090	arg1	cytoplasm					1099:1107	the cytoplasm	1095:1107	the cytoplasm	1095:1107	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	6	3	theme	N-linked	923:930	arg1	deficiency					946:955	N-linked glycosylation deficiency	923:955	N-linked glycosylation deficiency	923:955	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	5	4	theme	glycosylation	715:727	arg1	site					729:732	the glycosylation site	711:732	the glycosylation site	711:732	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	3	5	from	attempt	364:370	arg1	study					354:358	this study	349:358	this study	349:358	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	7	6	theme	flow	1058:1061	arg1	cytometry					1063:1071	flow cytometry	1058:1071	flow cytometry	1058:1071	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	1	7	theme	prion	165:169	arg1	proteins					171:178	prion proteins	165:178	prion proteins	165:178	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	4	8	theme	monoglycosylated	526:541	arg1	N181D					551:555	N181D	551:555	N181D	551:555	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	8	theme	monoglycosylated	526:541	arg1	mutants					543:549	its monoglycosylated mutants	522:549	its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D	522:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	8	theme	monoglycosylated	526:541	arg1	N197D					558:562	N197D	558:562	N197D	558:562	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	8	theme	monoglycosylated	526:541	arg1	T199N/N181D/N197D					569:585	T199N/N181D/N197D	569:585	T199N/N181D/N197D	569:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	7	9	theme	greater	1131:1137	arg1	resistance					1142:1151	considerably greater PK resistance	1118:1151	considerably greater PK resistance	1118:1151	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	7	10	theme	plasma	1264:1269	arg1	membrane					1271:1278	the plasma membrane	1260:1278	the plasma membrane	1260:1278	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	7	11	theme	PK	1139:1140	arg1	resistance					1142:1151	considerably greater PK resistance	1118:1151	considerably greater PK resistance	1118:1151	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	6	12	theme	mutant	836:841	arg1	V180I					843:847	the pathological mutant V180I	819:847	the pathological mutant V180I	819:847	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	9	13	theme	PrP	1493:1495	arg1	localization					1497:1508	PrP localization	1493:1508	PrP localization on the plasma membrane	1493:1531	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	2	14	theme	protein	264:270	arg1	structure					278:286	prion protein (PrP) structure	258:286	prion protein (PrP) structure	258:286	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	6	15	theme	pathological	823:834	arg1	V180I					843:847	the pathological mutant V180I	819:847	the pathological mutant V180I	819:847	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	1	16	from	misfolding	151:160	arg1	species					217:223	cervid species	210:223	cervid species	210:223	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	1	16	from	misfolding	151:160	arg1	humans					183:188	humans	183:188	humans	183:188	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	1	16	from	misfolding	151:160	arg1	sheep					199:203	sheep	199:203	sheep	199:203	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	1	16	from	misfolding	151:160	arg1	cattle					191:196	cattle	191:196	cattle	191:196	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	2	17	theme	prion	258:262	arg1	protein					264:270	prion protein	258:270	prion protein (PrP) structure	258:286	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	2	17	theme	prion	258:262	arg1	PrP					273:275	PrP	273:275	PrP	273:275	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	1	18	theme	proteins	171:178	arg1	misfolding					151:160	the misfolding	147:160	the misfolding of prion proteins in humans, cattle, sheep, and cervid species	147:223	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	5	19	theme	altered	688:694	arg1	residue					696:702	an altered residue	685:702	an altered residue within the glycosylation site	685:732	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	4	20	gly	monoglycosylated	526:541	arg1	N181D					551:555	N181D	551:555	N181D	551:555	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	20	gly	monoglycosylated	526:541	arg1	mutants					543:549	its monoglycosylated mutants	522:549	its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D	522:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	20	gly	monoglycosylated	526:541	arg1	N197D					558:562	N197D	558:562	N197D	558:562	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	20	gly	monoglycosylated	526:541	arg1	T199N/N181D/N197D					569:585	T199N/N181D/N197D	569:585	T199N/N181D/N197D	569:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	5	21	theme	PrP	757:759	arg1	mutant					761:766	an unglycosylated PrP mutant	739:766	an unglycosylated PrP mutant	739:766	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	5	22	theme	unglycosylated	742:755	arg1	mutant					761:766	an unglycosylated PrP mutant	739:766	an unglycosylated PrP mutant	739:766	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	7	23	from	cytoplasm	1099:1107	arg1	located					1084:1090	located	1084:1090	located	1084:1090	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	6	24	theme	plasma	1010:1015	arg1	membrane					1017:1024	the plasma membrane	1006:1024	the plasma membrane	1006:1024	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	5	25	with	mutant	761:766	arg1	residue					696:702	an altered residue	685:702	an altered residue within the glycosylation site	685:732	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	2	26	gly	glycosylation	241:253	arg1	protein					264:270	prion protein	258:270	prion protein (PrP) structure	258:286	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	2	26	gly	glycosylation	241:253	arg1	PrP					273:275	PrP	273:275	PrP	273:275	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	9	27	theme	plasma	1517:1522	arg1	membrane					1524:1531	the plasma membrane	1513:1531	the plasma membrane	1513:1531	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	2	28	from	effects	230:236	arg1	function					292:299	function	292:299	function	292:299	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	2	28	from	effects	230:236	arg1	structure					278:286	prion protein (PrP) structure	258:286	prion protein (PrP) structure	258:286	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	6	29	theme	PrP	999:1001	arg1	localization					977:988	the correct localization	965:988	the correct localization of human PrP at the plasma membrane	965:1024	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	7	30	theme	located	1084:1090	arg1	PrP					1080:1082	human PrP	1074:1082	human PrP located in the cytoplasm	1074:1107	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	4	31	theme	wild-type	504:512	arg1	PrP					514:516	wild-type PrP	504:516	wild-type PrP	504:516	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	1	32	theme	Prion	108:112	arg1	diseases					114:121	Prion diseases	108:121	Prion diseases	108:121	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	6	33	theme	human	993:997	arg1	PrP					999:1001	human PrP	993:1001	human PrP	993:1001	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	5	34	gly	glycosylation	715:727	arg2	site					729:732	the glycosylation site	711:732	the glycosylation site	711:732	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	8	35	theme	human	1328:1332	arg1	cytotoxicity					1338:1349	human PrP cytotoxicity	1328:1349	human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126	1328:1405	Furthermore, glycosylation deficiency enhances human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126.
30135544	7	36	theme	located	1249:1255	arg1	PrP					1245:1247	PrP	1245:1247	PrP located on the plasma membrane	1245:1278	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	7	37	theme	human	1074:1078	arg1	PrP					1080:1082	human PrP	1074:1082	human PrP located in the cytoplasm	1074:1107	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	6	38	theme	membranous	875:884	arg1	mix					868:870	an equal mix	859:870	an equal mix of membranous and cytoplasmic PrP	859:904	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	8	39	theme	peptide	1387:1393	arg1	PrP					1395:1397	the toxic prion peptide PrP 106-126	1371:1405	the toxic prion peptide PrP 106-126	1371:1405	Furthermore, glycosylation deficiency enhances human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126.
30135544	3	40	theme	glycosylation	400:412	arg1	effects					389:395	the effects	385:395	the effects of glycosylation on the aggregation and toxicity of human PrP	385:457	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	4	41	theme	plasma	617:622	arg1	membrane					624:631	the plasma membrane	613:631	the plasma membrane	613:631	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	42	theme	immunocytochemical	475:492	arg1	staining					494:501	immunocytochemical staining	475:501	immunocytochemical staining	475:501	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	5	43	theme	pathological	660:671	arg1	mutant					673:678	a pathological mutant	658:678	a pathological mutant with an altered residue within the glycosylation site	658:732	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	4	44	dep	mutants	543:549	arg1	N181D					551:555	N181D	551:555	N181D	551:555	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	44	dep	mutants	543:549	arg1	mutants					543:549	its monoglycosylated mutants	522:549	its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D	522:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	44	dep	mutants	543:549	arg1	N197D					558:562	N197D	558:562	N197D	558:562	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	44	dep	mutants	543:549	arg1	T199N/N181D/N197D					569:585	T199N/N181D/N197D	569:585	T199N/N181D/N197D	569:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	5	45	gly	unglycosylated	742:755	arg1	mutant					761:766	an unglycosylated PrP mutant	739:766	an unglycosylated PrP mutant	739:766	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	6	46	theme	correct	969:975	arg1	localization					977:988	the correct localization	965:988	the correct localization of human PrP at the plasma membrane	965:1024	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	0	47	theme	Prion	62:66	arg1	Protein					68:74	Human Prion Protein	56:74	Human Prion Protein	56:74	Glycosylation Significantly Inhibits the Aggregation of Human Prion Protein and Decreases Its Cytotoxicity.
30135544	6	48	theme	cytoplasmic	890:900	arg1	mix					868:870	an equal mix	859:870	an equal mix of membranous and cytoplasmic PrP	859:904	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	5	49	with	mutant	673:678	arg1	residue					696:702	an altered residue	685:702	an altered residue within the glycosylation site	685:732	In contrast, PrP F198S, a pathological mutant with an altered residue within the glycosylation site, and an unglycosylated PrP mutant, N181D/N197D, primarily exist in the cytoplasm.
30135544	7	50	theme	cellular	1220:1227	arg1	levels					1233:1238	considerably higher cellular ROS levels	1200:1238	considerably higher cellular ROS levels than PrP located on the plasma membrane	1200:1278	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	0	51	theme	Human	56:60	arg1	Protein					68:74	Human Prion Protein	56:74	Human Prion Protein	56:74	Glycosylation Significantly Inhibits the Aggregation of Human Prion Protein and Decreases Its Cytotoxicity.
30135544	6	52	theme	equal	862:866	arg1	mix					868:870	an equal mix	859:870	an equal mix of membranous and cytoplasmic PrP	859:904	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	3	53	gly	glycosylation	400:412	arg1	PrP					455:457	human PrP	449:457	human PrP	449:457	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	3	54	theme	human	449:453	arg1	PrP					455:457	human PrP	449:457	human PrP	449:457	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	8	55	theme	toxic	1375:1379	arg1	PrP					1395:1397	the toxic prion peptide PrP 106-126	1371:1405	the toxic prion peptide PrP 106-126	1371:1405	Furthermore, glycosylation deficiency enhances human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126.
30135544	6	56	dep	membranous	875:884	arg1	PrP					902:904	PrP	902:904	PrP	902:904	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	2	57	theme	glycosylation	241:253	arg1	effects					230:236	The effects	226:236	The effects of glycosylation on prion protein (PrP) structure and function	226:299	The effects of glycosylation on prion protein (PrP) structure and function have not been thoroughly elucidated to date.
30135544	9	58	theme	human	1587:1591	arg1	PrP					1593:1595	human PrP	1587:1595	human PrP	1587:1595	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	6	59	link	N-linked	923:930	arg1	deficiency					946:955	N-linked glycosylation deficiency	923:955	N-linked glycosylation deficiency	923:955	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	8	60	theme	glycosylation	1294:1306	arg1	deficiency					1308:1317	glycosylation deficiency	1294:1317	glycosylation deficiency	1294:1317	Furthermore, glycosylation deficiency enhances human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126.
30135544	4	61	attach	attached	601:608	arg2	T199N/N181D/N197D					569:585	T199N/N181D/N197D	569:585	T199N/N181D/N197D	569:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	61	attach	attached	601:608	arg2	mutants					543:549	its monoglycosylated mutants	522:549	its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D	522:585	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	61	attach	attached	601:608	arg2	PrP					514:516	wild-type PrP	504:516	wild-type PrP	504:516	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	61	attach	attached	601:608	arg2	N181D					551:555	N181D	551:555	N181D	551:555	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	61	attach	attached	601:608	arg1	membrane					624:631	the plasma membrane	613:631	the plasma membrane	613:631	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	4	61	attach	attached	601:608	arg2	N197D					558:562	N197D	558:562	N197D	558:562	As revealed by immunocytochemical staining, wild-type PrP and its monoglycosylated mutants N181D, N197D, and T199N/N181D/N197D are primarily attached to the plasma membrane.
30135544	9	62	from	localization	1497:1508	arg1	membrane					1524:1531	the plasma membrane	1513:1531	the plasma membrane	1513:1531	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	7	63	theme	higher	1213:1218	arg1	levels					1233:1238	considerably higher cellular ROS levels	1200:1238	considerably higher cellular ROS levels than PrP located on the plasma membrane	1200:1278	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	1	64	theme	cervid	210:215	arg1	species					217:223	cervid species	210:223	cervid species	210:223	Prion diseases are primarily caused by the misfolding of prion proteins in humans, cattle, sheep, and cervid species.
30135544	7	65	theme	aggregation	1157:1167	arg1	ability					1169:1175	aggregation ability	1157:1175	aggregation ability	1157:1175	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	8	66	theme	PrP	1334:1336	arg1	cytotoxicity					1338:1349	human PrP cytotoxicity	1328:1349	human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126	1328:1405	Furthermore, glycosylation deficiency enhances human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126.
30135544	8	67	theme	prion	1381:1385	arg1	PrP					1395:1397	the toxic prion peptide PrP 106-126	1371:1405	the toxic prion peptide PrP 106-126	1371:1405	Furthermore, glycosylation deficiency enhances human PrP cytotoxicity induced by MG132 or the toxic prion peptide PrP 106-126.
30135544	6	68	from	membrane	1017:1024	arg1	localization					977:988	the correct localization	965:988	the correct localization of human PrP at the plasma membrane	965:1024	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
30135544	0	69	theme	Protein	68:74	arg1	Aggregation					41:51	the Aggregation	37:51	the Aggregation of Human Prion Protein	37:74	Glycosylation Significantly Inhibits the Aggregation of Human Prion Protein and Decreases Its Cytotoxicity.
30135544	3	70	dep	aggregation	421:431	arg1	the					417:419	the	417:419	the	417:419	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	3	71	from	effects	389:395	arg1	toxicity					437:444	toxicity	437:444	toxicity	437:444	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	3	71	from	effects	389:395	arg1	aggregation					421:431	aggregation	421:431	aggregation	421:431	In this study, we attempt to elucidate the effects of glycosylation on the aggregation and toxicity of human PrP.
30135544	9	72	theme	necessary	1459:1467	arg1	aggregation					1572:1582	the aggregation	1568:1582	the aggregation of human PrP	1568:1595	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	9	72	theme	necessary	1459:1467	arg1	cofactor					1469:1476	a necessary cofactor	1457:1476	a necessary cofactor	1457:1476	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	9	72	theme	necessary	1459:1467	arg1	glycosylation					1435:1447	glycosylation	1435:1447	glycosylation	1435:1447	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	9	72	theme	necessary	1459:1467	arg1	cytotoxicity					1615:1626	its cytotoxicity	1611:1626	its cytotoxicity	1611:1626	Therefore, we propose that glycosylation acts as a necessary cofactor in determining PrP localization on the plasma membrane and that it significantly inhibits the aggregation of human PrP and decreases its cytotoxicity.
30135544	7	73	theme	ROS	1229:1231	arg1	levels					1233:1238	considerably higher cellular ROS levels	1200:1238	considerably higher cellular ROS levels than PrP located on the plasma membrane	1200:1278	As shown by immunoblotting and flow cytometry, human PrP located in the cytoplasm displays considerably greater PK resistance and aggregation ability and is associated with considerably higher cellular ROS levels than PrP located on the plasma membrane.
30135544	6	74	theme	glycosylation	932:944	arg1	deficiency					946:955	N-linked glycosylation deficiency	923:955	N-linked glycosylation deficiency	923:955	In the pathological mutant V180I, there is an equal mix of membranous and cytoplasmic PrP, indicating that N-linked glycosylation deficiency impairs the correct localization of human PrP at the plasma membrane.
29717387	9	0	theme	microglia	1103:1111	arg1	activation					1089:1098	the inflammatory activation	1072:1098	the inflammatory activation	1072:1098	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	2	1	theme	transcriptional	216:230	arg1	receptor					273:280	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ	195:282	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ)	195:290	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	2	1	theme	transcriptional	216:230	arg1	PPARγ					285:289	PPARγ	285:289	PPARγ	285:289	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	4	2	link	N-linked	457:464	arg1	sites					480:484	two N-linked glycosylation sites	453:484	two N-linked glycosylation sites in its DNA binding domain (DBD)	453:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	3	3	dep	Ι	356:356	arg1	4GalT1					363:368	4GalT1	363:368	4GalT1	363:368	β-1,4-Galactosyltransferase Ι (β1, 4GalT1) mediates N-glycosylation.
29717387	3	3	dep	Ι	356:356	arg1	β1					359:360	β1	359:360	β1	359:360	β-1,4-Galactosyltransferase Ι (β1, 4GalT1) mediates N-glycosylation.
29717387	9	4	contain	has	1120:1122	arg1	activation					1089:1098	the inflammatory activation	1072:1098	the inflammatory activation	1072:1098	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	9	4	contain	has	1120:1122	arg2	implications					1124:1135	implications	1124:1135	implications for potential therapies for CNS inflammatory diseases	1124:1189	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	4	5	theme	PPARγ	435:439	arg1	N-glycosylation					416:430	the N-glycosylation	412:430	the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD),	412:517	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	6	gly	glycosylation	466:478	arg2	sites					480:484	two N-linked glycosylation sites	453:484	two N-linked glycosylation sites in its DNA binding domain (DBD)	453:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	6	gly	glycosylation	466:478	arg2	two					453:455	two	453:455	two	453:455	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	7	gly	N-glycosylation	416:430	arg1	PPARγ					435:439	PPARγ	435:439	PPARγ	435:439	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	7	gly	N-glycosylation	416:430	arg1	sites					480:484	two N-linked glycosylation sites	453:484	two N-linked glycosylation sites in its DNA binding domain (DBD)	453:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	7	gly	N-glycosylation	416:430	arg1	study					405:409	this study	400:409	this study	400:409	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	8	8	theme	anti-inflammatory	950:966	arg1	functions					968:976	anti-inflammatory functions	950:976	anti-inflammatory functions	950:976	β1, 4GalT1 promoted PPARγ's anti-transcription and anti-inflammatory functions.
29717387	9	9	theme	potential	1141:1149	arg1	therapies					1151:1159	potential therapies	1141:1159	potential therapies for CNS inflammatory diseases	1141:1189	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	4	10	theme	binding	497:503	arg1	DBD					513:515	DBD	513:515	DBD	513:515	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	10	theme	binding	497:503	arg1	domain					505:510	its DNA binding domain	489:510	its DNA binding domain (DBD)	489:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	6	11	theme	anti-inflammatory	735:751	arg1	function					753:760	the anti-inflammatory function	731:760	the anti-inflammatory function of unglycosylated PPARγ	731:784	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29717387	1	12	theme	inflammatory	91:102	arg1	activation					104:113	The inflammatory activation	87:113	The inflammatory activation of microglia	87:126	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	4	13	from	domain	505:510	arg1	N-glycosylation					416:430	the N-glycosylation	412:430	the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD),	412:517	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	7	14	theme	PPARγ	878:882	arg1	glycosylation					884:896	PPARγ glycosylation	878:896	PPARγ glycosylation	878:896	In addition, β1, 4GalT1 was shown to interact with PPARγ and to mediate PPARγ glycosylation.
29717387	4	15	theme	N-linked	457:464	arg1	sites					480:484	two N-linked glycosylation sites	453:484	two N-linked glycosylation sites in its DNA binding domain (DBD)	453:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	16	from	N-glycosylation	416:430	arg1	DBD					513:515	DBD	513:515	DBD	513:515	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	16	from	N-glycosylation	416:430	arg1	domain					505:510	its DNA binding domain	489:510	its DNA binding domain (DBD)	489:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	1	17	theme	microglia	118:126	arg1	activation					104:113	The inflammatory activation	87:113	The inflammatory activation of microglia	87:126	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	6	18	theme	microglia	714:722	arg1	activation					700:709	the inflammatory activation	683:709	the inflammatory activation of microglia	683:722	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29717387	0	19	theme	PPARγ	17:21	arg1	N-Glycosylation					23:37	PPARγ N-Glycosylation	17:37	PPARγ N-Glycosylation to Attenuate Microglia Inflammatory Activation	17:84	β4GalT1 Mediates PPARγ N-Glycosylation to Attenuate Microglia Inflammatory Activation.
29717387	3	20	theme	β-1,4-Galactosyltransferase	328:354	arg1	Ι					356:356	β-1,4-Galactosyltransferase Ι	328:356	β-1,4-Galactosyltransferase Ι (β1, 4GalT1)	328:369	β-1,4-Galactosyltransferase Ι (β1, 4GalT1) mediates N-glycosylation.
29717387	9	21	theme	CNS	1165:1167	arg1	diseases					1182:1189	CNS inflammatory diseases	1165:1189	CNS inflammatory diseases	1165:1189	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	4	22	theme	sites	480:484	arg1	N-glycosylation					416:430	the N-glycosylation	412:430	the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD),	412:517	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	9	23	theme	inflammatory	1169:1180	arg1	diseases					1182:1189	CNS inflammatory diseases	1165:1189	CNS inflammatory diseases	1165:1189	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	9	24	theme	PPARγ	1039:1043	arg1	glycosylation					1045:1057	PPARγ glycosylation	1039:1057	PPARγ glycosylation	1039:1057	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	1	25	contain	has	128:130	arg2	effects					145:151	double-edged effects	132:151	double-edged effects	132:151	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	1	25	contain	has	128:130	arg1	activation					104:113	The inflammatory activation	87:113	The inflammatory activation of microglia	87:126	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	4	26	from	sites	480:484	arg1	DBD					513:515	DBD	513:515	DBD	513:515	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	26	from	sites	480:484	arg1	domain					505:510	its DNA binding domain	489:510	its DNA binding domain (DBD)	489:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	27	theme	DNA	493:495	arg1	DBD					513:515	DBD	513:515	DBD	513:515	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	27	theme	DNA	493:495	arg1	domain					505:510	its DNA binding domain	489:510	its DNA binding domain (DBD)	489:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	5	28	theme	sites	554:558	arg1	Disruption					535:544	Disruption	535:544	Disruption of both sites by site-directed mutagenesis	535:587	Disruption of both sites by site-directed mutagenesis completely abrogated the N-glycosylation of PPARγ.
29717387	0	29	theme	Inflammatory	62:73	arg1	Activation					75:84	Microglia Inflammatory Activation	52:84	Microglia Inflammatory Activation	52:84	β4GalT1 Mediates PPARγ N-Glycosylation to Attenuate Microglia Inflammatory Activation.
29717387	6	30	dep	wild-type	645:653	arg1	WT					656:657	WT	656:657	WT	656:657	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29717387	1	31	theme	double-edged	132:143	arg1	effects					145:151	double-edged effects	132:151	double-edged effects	132:151	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	0	32	theme	Microglia	52:60	arg1	Activation					75:84	Microglia Inflammatory Activation	52:84	Microglia Inflammatory Activation	52:84	β4GalT1 Mediates PPARγ N-Glycosylation to Attenuate Microglia Inflammatory Activation.
29717387	2	33	theme	peroxisome	239:248	arg1	receptor					273:280	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ	195:282	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ)	195:290	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	2	33	theme	peroxisome	239:248	arg1	PPARγ					285:289	PPARγ	285:289	PPARγ	285:289	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	2	34	theme	proliferator-activated	250:271	arg1	receptor					273:280	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ	195:282	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ)	195:290	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	2	34	theme	proliferator-activated	250:271	arg1	PPARγ					285:289	PPARγ	285:289	PPARγ	285:289	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	5	35	theme	site-directed	563:575	arg1	mutagenesis					577:587	site-directed mutagenesis	563:587	site-directed mutagenesis	563:587	Disruption of both sites by site-directed mutagenesis completely abrogated the N-glycosylation of PPARγ.
29717387	6	36	theme	inflammatory	687:698	arg1	activation					700:709	the inflammatory activation	683:709	the inflammatory activation of microglia	683:722	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29717387	6	37	theme	wild-type	645:653	arg1	transfection					660:671	PPAR wild-type (WT) transfection	640:671	PPAR wild-type (WT) transfection	640:671	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29717387	2	38	theme	factor	232:237	arg1	receptor					273:280	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ	195:282	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ)	195:290	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	2	38	theme	factor	232:237	arg1	PPARγ					285:289	PPARγ	285:289	PPARγ	285:289	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	5	39	theme	PPARγ	633:637	arg1	N-glycosylation					614:628	the N-glycosylation	610:628	the N-glycosylation of PPARγ	610:637	Disruption of both sites by site-directed mutagenesis completely abrogated the N-glycosylation of PPARγ.
29717387	2	40	theme	inflammatory	305:316	arg1	response					318:325	the inflammatory response	301:325	the inflammatory response	301:325	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	4	41	theme	glycosylation	466:478	arg1	sites					480:484	two N-linked glycosylation sites	453:484	two N-linked glycosylation sites in its DNA binding domain (DBD)	453:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	1	42	theme	central	156:162	arg1	system					172:177	central nervous system	156:177	central nervous system (CNS) diseases	156:192	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	1	42	theme	central	156:162	arg1	CNS					180:182	CNS	180:182	CNS	180:182	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	9	43	theme	inflammatory	1076:1087	arg1	activation					1089:1098	the inflammatory activation	1072:1098	the inflammatory activation	1072:1098	Collectively, our findings define that β-1, 4GalT1 mediated PPARγ glycosylation to attenuate the inflammatory activation of microglia, which has implications for potential therapies for CNS inflammatory diseases.
29717387	4	44	from	PPARγ	435:439	arg1	DBD					513:515	DBD	513:515	DBD	513:515	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	4	44	from	PPARγ	435:439	arg1	domain					505:510	its DNA binding domain	489:510	its DNA binding domain (DBD)	489:516	In this study, the N-glycosylation of PPARγ, as well as two N-linked glycosylation sites in its DNA binding domain (DBD), was identified.
29717387	2	45	theme	ligand-activated	199:214	arg1	receptor					273:280	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ	195:282	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ)	195:290	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	2	45	theme	ligand-activated	199:214	arg1	PPARγ					285:289	PPARγ	285:289	PPARγ	285:289	The ligand-activated transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ) inhibits the inflammatory response.
29717387	6	46	theme	PPARγ	780:784	arg1	function					753:760	the anti-inflammatory function	731:760	the anti-inflammatory function of unglycosylated PPARγ	731:784	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29717387	1	47	theme	nervous	164:170	arg1	system					172:177	central nervous system	156:177	central nervous system (CNS) diseases	156:192	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	1	47	theme	nervous	164:170	arg1	CNS					180:182	CNS	180:182	CNS	180:182	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	5	48	gly	N-glycosylation	614:628	arg1	PPARγ					633:637	PPARγ	633:637	PPARγ	633:637	Disruption of both sites by site-directed mutagenesis completely abrogated the N-glycosylation of PPARγ.
29717387	6	49	theme	unglycosylated	765:778	arg1	PPARγ					780:784	unglycosylated PPARγ	765:784	unglycosylated PPARγ	765:784	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29717387	1	50	theme	system	172:177	arg1	diseases					185:192	central nervous system (CNS) diseases	156:192	central nervous system (CNS) diseases	156:192	The inflammatory activation of microglia has double-edged effects in central nervous system (CNS) diseases.
29717387	6	51	gly	unglycosylated	765:778	arg1	PPARγ					780:784	unglycosylated PPARγ	765:784	unglycosylated PPARγ	765:784	PPAR wild-type (WT) transfection inhibited the inflammatory activation of microglia, while the anti-inflammatory function of unglycosylated PPARγ was down-regulated.
29531238	7	0	theme	somatic	1161:1167	arg1	variants					1169:1176	all identified cancer somatic variants	1139:1176	all identified cancer somatic variants causing potential loss or gain of glycosylation	1139:1224	Of all identified cancer somatic variants causing potential loss or gain of glycosylation, only 36 have previously known disease associations.
29531238	4	1	from	sites	805:809	arg1	glycoproteins					820:832	4,412 glycoproteins	814:832	4,412 glycoproteins	814:832	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	2	2	theme	glycosylation	345:357	arg1	NLGs					368:371	NLGs	368:371	NLGs	368:371	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	2	theme	glycosylation	345:357	arg1	sequons					359:365	human N-linked glycosylation sequons	330:365	human N-linked glycosylation sequons (NLGs)	330:372	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	5	3	from	NLGs	954:957	arg1	proteins					968:975	7,356 proteins	962:975	7,356 proteins in cancer samples	962:993	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	8	4	theme	rank	1403:1406	arg1	biomarkers					1431:1440	rank potential cancer nsSNV biomarkers	1403:1440	rank potential cancer nsSNV biomarkers for experimental validation	1403:1468	Although this work is computational, it builds on existing genomics and glycobiology research to promote identification and rank potential cancer nsSNV biomarkers for experimental validation.
29531238	2	5	theme	N-linked	336:343	arg1	NLGs					368:371	NLGs	368:371	NLGs	368:371	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	5	theme	N-linked	336:343	arg1	sequons					359:365	human N-linked glycosylation sequons	330:365	human N-linked glycosylation sequons (NLGs)	330:372	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	8	6	theme	potential	1408:1416	arg1	biomarkers					1431:1440	rank potential cancer nsSNV biomarkers	1403:1440	rank potential cancer nsSNV biomarkers for experimental validation	1403:1468	Although this work is computational, it builds on existing genomics and glycobiology research to promote identification and rank potential cancer nsSNV biomarkers for experimental validation.
29531238	7	7	theme	identified	1143:1152	arg1	variants					1169:1176	all identified cancer somatic variants	1139:1176	all identified cancer somatic variants causing potential loss or gain of glycosylation	1139:1224	Of all identified cancer somatic variants causing potential loss or gain of glycosylation, only 36 have previously known disease associations.
29531238	2	8	theme	sequon	602:607	arg1	gain					580:583	gain	580:583	gain of glycosylation sequon	580:607	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	8	theme	sequon	602:607	arg1	loss					572:575	the expected loss	559:575	the expected loss	559:575	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	4	9	theme	validated	795:803	arg1	sites					805:809	experimentally validated sites	780:809	experimentally validated sites on 4,412 glycoproteins	780:832	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	4	9	theme	validated	795:803	arg1	%					762:762	Only 27.4%	753:762	Only 27.4% of all NLGs	753:774	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	4	9	theme	validated	795:803	arg1	NLGs					771:774	all NLGs	767:774	all NLGs	767:774	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	5	10	theme	somatic-only	927:938	arg1	nsSNVs					940:945	12,939 somatic-only nsSNVs	920:945	12,939 somatic-only nsSNVs	920:945	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	2	11	theme	variation	530:538	arg1	data					540:543	cancer variation data	523:543	cancer variation data	523:543	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	3	12	theme	NLGs	697:700	arg1	total					674:678	a total	672:678	a total of 59,341 unique NLGs (includes predicted and experimentally validated)	672:750	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	2	13	theme	glycosylation	588:600	arg1	sequon					602:607	glycosylation sequon	588:607	glycosylation sequon	588:607	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	5	14	from	proteins	968:975	arg1	samples					987:993	cancer samples	980:993	cancer samples	980:993	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	2	15	theme	cancer	523:528	arg1	data					540:543	cancer variation data	523:543	cancer variation data	523:543	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	16	link	N-linked	336:343	arg1	NLGs					368:371	NLGs	368:371	NLGs	368:371	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	16	link	N-linked	336:343	arg1	sequons					359:365	human N-linked glycosylation sequons	330:365	human N-linked glycosylation sequons (NLGs)	330:372	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	8	17	theme	experimental	1446:1457	arg1	validation					1459:1468	experimental validation	1446:1468	experimental validation	1446:1468	Although this work is computational, it builds on existing genomics and glycobiology research to promote identification and rank potential cancer nsSNV biomarkers for experimental validation.
29531238	6	18	gly	glycoproteins	1081:1093	arg1	glycoproteins					1081:1093	40 glycoproteins	1078:1093	40 glycoproteins	1078:1093	nsSNVs causing loss of 24 NLGs on 23 glycoproteins and nsSNVs creating 41 NLGs on 40 glycoproteins are identified in three or more cancers.
29531238	5	19	from	NLGs	893:896	arg1	nsSNVs					940:945	12,939 somatic-only nsSNVs	920:945	12,939 somatic-only nsSNVs	920:945	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	5	19	from	NLGs	893:896	arg1	proteins					907:914	5,204 proteins	901:914	5,204 proteins	901:914	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	2	20	theme	single-nucleotide	462:478	arg1	nsSNV					491:495	nsSNV	491:495	nsSNV	491:495	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	20	theme	single-nucleotide	462:478	arg1	variation					480:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation	416:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV)	416:496	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	3	21	theme	unique	690:695	arg1	NLGs					697:700	59,341 unique NLGs	683:700	59,341 unique NLGs (includes predicted and experimentally validated)	683:750	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	5	22	theme	5,204	901:905	arg1	proteins					907:914	5,204 proteins	901:914	5,204 proteins	901:914	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	1	23	theme	sequence	192:199	arg1	curation					209:216	sequence feature curation	192:216	sequence feature curation	192:216	Despite availability of sequence site-specific information resulting from years of sequencing and sequence feature curation, there have been few efforts to integrate and annotate this information.
29531238	2	24	theme	nonsynonymous	448:460	arg1	nsSNV					491:495	nsSNV	491:495	nsSNV	491:495	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	24	theme	nonsynonymous	448:460	arg1	variation					480:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation	416:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV)	416:496	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	4	25	theme	4,412	814:818	arg1	glycoproteins					820:832	4,412 glycoproteins	814:832	4,412 glycoproteins	814:832	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	1	26	theme	feature	201:207	arg1	curation					209:216	sequence feature curation	192:216	sequence feature curation	192:216	Despite availability of sequence site-specific information resulting from years of sequencing and sequence feature curation, there have been few efforts to integrate and annotate this information.
29531238	2	27	theme	somatic	440:446	arg1	nsSNV					491:495	nsSNV	491:495	nsSNV	491:495	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	27	theme	somatic	440:446	arg1	variation					480:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation	416:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV)	416:496	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	28	theme	expected	563:570	arg1	loss					572:575	the expected loss	559:575	the expected loss	559:575	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	0	29	link	N-linked	17:24	arg1	glycosylation					26:38	N-linked glycosylation	17:38	N-linked glycosylation	17:38	Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.
29531238	5	30	dep	cancer	851:856	arg1	respect					840:846	respect	840:846	respect	840:846	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	3	31	dep	find	613:616	arg1	have					646:649	have	646:649	find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated)	613:750	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	2	32	theme	glycosylation-impacting	416:438	arg1	nsSNV					491:495	nsSNV	491:495	nsSNV	491:495	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	32	theme	glycosylation-impacting	416:438	arg1	variation					480:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation	416:488	glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV)	416:496	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	3	33	theme	proteins	637:644	arg1	proteins					637:644	all human proteins	627:644	all human proteins	627:644	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	3	33	theme	proteins	637:644	arg1	%					622:622	75.8%	618:622	75.8% of all human proteins	618:644	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	5	34	theme	somatic-only	865:876	arg1	nsSNVs					878:883	8,895 somatic-only nsSNVs	859:883	8,895 somatic-only nsSNVs	859:883	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	7	35	theme	disease	1257:1263	arg1	associations					1265:1276	disease associations	1257:1276	disease associations	1257:1276	Of all identified cancer somatic variants causing potential loss or gain of glycosylation, only 36 have previously known disease associations.
29531238	0	36	theme	glycosylation	26:38	arg1	gain					9:12	gain	9:12	gain	9:12	Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.
29531238	0	36	theme	glycosylation	26:38	arg1	Loss					0:3	Loss	0:3	Loss	0:3	Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.
29531238	0	37	from	variation	73:81	arg1	cancer					86:91	cancer	86:91	cancer	86:91	Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.
29531238	5	38	theme	cancer	980:985	arg1	samples					987:993	cancer samples	980:993	cancer samples	980:993	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	6	39	theme	NLGs	1022:1025	arg1	loss					1011:1014	loss	1011:1014	loss of 24 NLGs on 23 glycoproteins and nsSNVs creating 41 NLGs on 40 glycoproteins	1011:1093	nsSNVs causing loss of 24 NLGs on 23 glycoproteins and nsSNVs creating 41 NLGs on 40 glycoproteins are identified in three or more cancers.
29531238	2	40	gly	glycosylation	588:600	arg2	sequon					602:607	glycosylation sequon	588:607	glycosylation sequon	588:607	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	0	41	theme	N-linked	17:24	arg1	glycosylation					26:38	N-linked glycosylation	17:38	N-linked glycosylation	17:38	Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.
29531238	2	42	gly	glycosylation	345:357	arg2	NLGs					368:371	NLGs	368:371	NLGs	368:371	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	42	gly	glycosylation	345:357	arg2	sequons					359:365	human N-linked glycosylation sequons	330:365	human N-linked glycosylation sequons (NLGs)	330:372	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	8	43	theme	nsSNV	1425:1429	arg1	biomarkers					1431:1440	rank potential cancer nsSNV biomarkers	1403:1440	rank potential cancer nsSNV biomarkers for experimental validation	1403:1468	Although this work is computational, it builds on existing genomics and glycobiology research to promote identification and rank potential cancer nsSNV biomarkers for experimental validation.
29531238	4	44	theme	NLGs	771:774	arg1	sites					805:809	experimentally validated sites	780:809	experimentally validated sites on 4,412 glycoproteins	780:832	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	4	44	theme	NLGs	771:774	arg1	%					762:762	Only 27.4%	753:762	Only 27.4% of all NLGs	753:774	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	4	44	theme	NLGs	771:774	arg1	NLGs					771:774	all NLGs	767:774	all NLGs	767:774	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	4	45	gly	glycoproteins	820:832	arg1	glycoproteins					820:832	4,412 glycoproteins	814:832	4,412 glycoproteins	814:832	Only 27.4% of all NLGs are experimentally validated sites on 4,412 glycoproteins.
29531238	3	46	theme	human	631:635	arg1	proteins					637:644	all human proteins	627:644	all human proteins	627:644	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	1	47	dep	sequencing	177:186	arg1	years					168:172	years	168:172	years	168:172	Despite availability of sequence site-specific information resulting from years of sequencing and sequence feature curation, there have been few efforts to integrate and annotate this information.
29531238	6	48	from	NLGs	1070:1073	arg1	glycoproteins					1081:1093	40 glycoproteins	1078:1093	40 glycoproteins	1078:1093	nsSNVs causing loss of 24 NLGs on 23 glycoproteins and nsSNVs creating 41 NLGs on 40 glycoproteins are identified in three or more cancers.
29531238	2	49	theme	human	330:334	arg1	NLGs					368:371	NLGs	368:371	NLGs	368:371	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	49	theme	human	330:334	arg1	sequons					359:365	human N-linked glycosylation sequons	330:365	human N-linked glycosylation sequons (NLGs)	330:372	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	2	50	theme	variation	480:488	arg1	cancer-relatedness					394:411	cancer-relatedness	394:411	cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV)	394:496	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	3	51	dep	NLGs	697:700	arg1	includes					703:710	includes	703:710	includes predicted and experimentally validated	703:749	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	6	52	gly	glycoproteins	1033:1045	arg1	glycoproteins					1033:1045	23 glycoproteins	1030:1045	23 glycoproteins	1030:1045	nsSNVs causing loss of 24 NLGs on 23 glycoproteins and nsSNVs creating 41 NLGs on 40 glycoproteins are identified in three or more cancers.
29531238	8	53	theme	glycobiology	1351:1362	arg1	research					1364:1371	genomics and glycobiology research	1338:1371	research	1364:1371	Although this work is computational, it builds on existing genomics and glycobiology research to promote identification and rank potential cancer nsSNV biomarkers for experimental validation.
29531238	1	54	theme	sequence	118:125	arg1	information					141:151	sequence site-specific information	118:151	sequence site-specific information resulting from years of sequencing and sequence feature curation	118:216	Despite availability of sequence site-specific information resulting from years of sequencing and sequence feature curation, there have been few efforts to integrate and annotate this information.
29531238	6	55	from	loss	1011:1014	arg1	nsSNVs					1051:1056	nsSNVs	1051:1056	nsSNVs	1051:1056	nsSNVs causing loss of 24 NLGs on 23 glycoproteins and nsSNVs creating 41 NLGs on 40 glycoproteins are identified in three or more cancers.
29531238	6	55	from	loss	1011:1014	arg1	glycoproteins					1033:1045	23 glycoproteins	1030:1045	23 glycoproteins	1030:1045	nsSNVs causing loss of 24 NLGs on 23 glycoproteins and nsSNVs creating 41 NLGs on 40 glycoproteins are identified in three or more cancers.
29531238	8	56	theme	genomics	1338:1345	arg1	research					1364:1371	genomics and glycobiology research	1338:1371	research	1364:1371	Although this work is computational, it builds on existing genomics and glycobiology research to promote identification and rank potential cancer nsSNV biomarkers for experimental validation.
29531238	1	57	theme	site-specific	127:139	arg1	information					141:151	sequence site-specific information	118:151	sequence site-specific information resulting from years of sequencing and sequence feature curation	118:216	Despite availability of sequence site-specific information resulting from years of sequencing and sequence feature curation, there have been few efforts to integrate and annotate this information.
29531238	5	58	theme	7,356	962:966	arg1	proteins					968:975	7,356 proteins	962:975	7,356 proteins in cancer samples	962:993	With respect to cancer, 8,895 somatic-only nsSNVs abolish NLGs in 5,204 proteins and 12,939 somatic-only nsSNVs create NLGs in 7,356 proteins in cancer samples.
29531238	1	59	theme	information	141:151	arg1	availability					102:113	availability	102:113	availability of sequence site-specific information resulting from years of sequencing and sequence feature curation	102:216	Despite availability of sequence site-specific information resulting from years of sequencing and sequence feature curation, there have been few efforts to integrate and annotate this information.
29531238	1	60	theme	few	235:237	arg1	efforts					239:245	few efforts	235:245	few efforts	235:245	Despite availability of sequence site-specific information resulting from years of sequencing and sequence feature curation, there have been few efforts to integrate and annotate this information.
29531238	0	61	theme	single-nucleotide	55:71	arg1	variation					73:81	single-nucleotide variation	55:81	single-nucleotide variation in cancer	55:91	Loss and gain of N-linked glycosylation sequons due to single-nucleotide variation in cancer.
29531238	8	62	theme	cancer	1418:1423	arg1	biomarkers					1431:1440	rank potential cancer nsSNV biomarkers	1403:1440	rank potential cancer nsSNV biomarkers for experimental validation	1403:1468	Although this work is computational, it builds on existing genomics and glycobiology research to promote identification and rank potential cancer nsSNV biomarkers for experimental validation.
29531238	7	63	theme	potential	1186:1194	arg1	loss					1196:1199	potential loss	1186:1199	potential loss	1186:1199	Of all identified cancer somatic variants causing potential loss or gain of glycosylation, only 36 have previously known disease associations.
29531238	2	64	theme	human	509:513	arg1	NLGs					515:518	human NLGs	509:518	human NLGs to cancer variation data	509:543	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	3	65	dep	includes	703:710	arg1	predicted					712:720	predicted	712:720	predicted	712:720	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	3	65	dep	includes	703:710	arg1	validated					741:749	validated	741:749	experimentally validated	726:749	We find 75.8% of all human proteins have at least one NLG for a total of 59,341 unique NLGs (includes predicted and experimentally validated).
29531238	7	66	theme	glycosylation	1212:1224	arg1	gain					1204:1207	gain	1204:1207	gain of glycosylation	1204:1224	Of all identified cancer somatic variants causing potential loss or gain of glycosylation, only 36 have previously known disease associations.
29531238	7	66	theme	glycosylation	1212:1224	arg1	loss					1196:1199	potential loss	1186:1199	potential loss	1186:1199	Of all identified cancer somatic variants causing potential loss or gain of glycosylation, only 36 have previously known disease associations.
29531238	2	67	theme	sequons	359:365	arg1	number					320:325	the number	316:325	the number of human N-linked glycosylation sequons (NLGs)	316:372	In this study, we update the number of human N-linked glycosylation sequons (NLGs), and we investigate cancer-relatedness of glycosylation-impacting somatic nonsynonymous single-nucleotide variation (nsSNV) by mapping human NLGs to cancer variation data and reporting the expected loss or gain of glycosylation sequon.
29531238	7	68	theme	cancer	1154:1159	arg1	variants					1169:1176	all identified cancer somatic variants	1139:1176	all identified cancer somatic variants causing potential loss or gain of glycosylation	1139:1224	Of all identified cancer somatic variants causing potential loss or gain of glycosylation, only 36 have previously known disease associations.
28614667	9	0	theme	Molecular	1645:1653	arg1	modeling					1655:1662	Molecular modeling	1645:1662	Molecular modeling	1645:1662	Molecular modeling suggested that this GlcNAc functions through an allosteric mechanism rather than by directly contacting the peptide.
28614667	8	1	theme	affinity	1623:1630	arg1	enhancement					1632:1642	the peptide affinity enhancement	1611:1642	the peptide affinity enhancement	1611:1642	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	6	2	from	N125	1087:1090	arg1	ECD					1113:1115	the CTR ECD	1105:1115	the CTR ECD	1105:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	2	from	N125	1087:1090	arg1	removal					1058:1064	PNGase F-catalyzed removal	1039:1064	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD	1039:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	1	3	theme	peptide	240:246	arg1	hormones					248:255	the peptide hormones calcitonin and amylin	236:277	the peptide hormones calcitonin and amylin	236:277	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	1	3	theme	peptide	240:246	arg1	amylin					272:277	amylin	272:277	amylin	272:277	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	1	3	theme	peptide	240:246	arg1	calcitonin					257:266	calcitonin	257:266	calcitonin	257:266	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	4	4	theme	CTR	581:583	arg1	N-glycosylation					585:599	CTR N-glycosylation	581:599	CTR N-glycosylation	581:599	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	8	5	theme	purified	1391:1398	arg1	mutants					1426:1432	purified N → Q CTR ECD glycan site mutants	1391:1432	purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1391:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	4	6	theme	receptor	657:664	arg1	ECD					688:690	ECD	688:690	ECD	688:690	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	4	6	theme	receptor	657:664	arg1	domain					680:685	purified calcitonin and amylin receptor extracellular domain	626:685	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	2	7	with	complex	406:412	arg1	proteins					447:454	receptor activity-modifying proteins	419:454	receptor activity-modifying proteins (RAMPs)	419:462	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	2	7	with	complex	406:412	arg1	RAMPs					457:461	RAMPs	457:461	RAMPs	457:461	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	6	8	theme	Endo	1162:1165	arg1	trimming					1179:1186	Endo H-catalyzed trimming	1162:1186	Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues	1162:1229	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	4	9	theme	domain	680:685	arg1	glycoforms					693:702	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	6	10	from	N73	1082:1084	arg1	ECD					1113:1115	the CTR ECD	1105:1115	the CTR ECD	1105:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	10	from	N73	1082:1084	arg1	removal					1058:1064	PNGase F-catalyzed removal	1039:1064	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD	1039:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	11	attach	removal	1058:1064	arg3	N130					1097:1100	N130	1097:1100	N130	1097:1100	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	11	attach	removal	1058:1064	arg3	N73					1082:1084	N73	1082:1084	N73	1082:1084	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	11	attach	removal	1058:1064	arg2	N-glycans					1069:1077	N-glycans	1069:1077	N-glycans	1069:1077	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	11	attach	removal	1058:1064	arg3	N125					1087:1090	N125	1087:1090	N125	1087:1090	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	5	12	theme	HEK293T	924:930	arg1	cells					932:936	HEK293T cells	924:936	HEK293T cells	924:936	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	4	13	theme	purified	626:633	arg1	ECD					688:690	ECD	688:690	ECD	688:690	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	4	13	theme	purified	626:633	arg1	domain					680:685	purified calcitonin and amylin receptor extracellular domain	626:685	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	0	14	theme	Hormone	127:133	arg1	Affinity					135:142	Peptide Hormone Affinity	119:142	Peptide Hormone Affinity	119:142	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	8	15	theme	PNGase	1448:1453	arg1	F					1455:1455	PNGase F	1448:1455	PNGase F	1448:1455	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	10	16	theme	N-linked	1824:1831	arg1	glycosylation					1833:1845	N-linked glycosylation	1824:1845	N-linked glycosylation	1824:1845	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	5	17	theme	CTR	904:906	arg1	ECD					908:910	CTR ECD	904:910	CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2)	904:1036	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	4	18	theme	fluorescence	708:719	arg1	polarization/anisotropy					721:743	fluorescence polarization/anisotropy	708:743	fluorescence polarization/anisotropy	708:743	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	8	19	theme	H	1466:1466	arg1	strategies					1478:1487	PNGase F and Endo H treatment strategies	1448:1487	PNGase F and Endo H treatment strategies	1448:1487	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	6	20	theme	GlcNAc	1215:1220	arg1	residues					1222:1229	single GlcNAc residues	1208:1229	single GlcNAc residues	1208:1229	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	8	21	theme	→	1402:1402	arg1	mutants					1426:1432	purified N → Q CTR ECD glycan site mutants	1391:1432	purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1391:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	4	22	gly	glycoforms	693:702	arg1	ECD					688:690	ECD	688:690	ECD	688:690	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	4	22	gly	glycoforms	693:702	arg1	domain					680:685	purified calcitonin and amylin receptor extracellular domain	626:685	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	10	23	theme	peptide	1854:1860	arg1	binding					1870:1876	the peptide hormone binding	1850:1876	the peptide hormone binding of a clinically relevant class B GPCR	1850:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	6	24	theme	F-catalyzed	1046:1056	arg1	removal					1058:1064	PNGase F-catalyzed removal	1039:1064	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD	1039:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	0	25	theme	Asparagine	19:28	arg1	N-Glycosylation					0:14	N-Glycosylation	0:14	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor	0:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	8	26	theme	mass	1493:1496	arg1	spectrometry					1498:1509	mass spectrometry	1493:1509	mass spectrometry	1493:1509	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	0	27	theme	Human	69:73	arg1	Receptor					86:93	the Human Calcitonin Receptor	65:93	the Human Calcitonin Receptor	65:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	4	28	gly	N-glycosylation	585:599	arg1	hormone					604:610	hormone binding	604:618	hormone binding	604:618	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	0	29	from	N-Glycosylation	0:14	arg1	Receptor					86:93	the Human Calcitonin Receptor	65:93	the Human Calcitonin Receptor	65:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	0	29	from	N-Glycosylation	0:14	arg1	Domain					55:60	the Extracellular Domain	37:60	the Extracellular Domain of the Human Calcitonin Receptor	37:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	0	30	theme	Receptor	86:93	arg1	Receptor					86:93	the Human Calcitonin Receptor	65:93	the Human Calcitonin Receptor	65:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	0	30	theme	Receptor	86:93	arg1	Domain					55:60	the Extracellular Domain	37:60	the Extracellular Domain of the Human Calcitonin Receptor	37:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	8	31	theme	affinities	1377:1386	arg1	Characterization					1341:1356	Characterization	1341:1356	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1341:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	5	32	theme	core	1009:1012	arg1	Man5GlcNAc2					1025:1035	Man5GlcNAc2	1025:1035	Man5GlcNAc2	1025:1035	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	5	32	theme	core	1009:1012	arg1	N-glycans					1014:1022	core N-glycans	1009:1022	core N-glycans (Man5GlcNAc2)	1009:1036	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	4	33	theme	titration	760:768	arg1	calorimetry					770:780	isothermal titration calorimetry	749:780	isothermal titration calorimetry	749:780	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	5	34	theme	HEK293S	976:982	arg1	cells					990:994	HEK293S GnTI- cells	976:994	HEK293S GnTI- cells	976:994	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	7	35	theme	ECD	1328:1330	arg1	complex					1332:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	Similar results were observed for an amylin receptor RAMP2-CTR ECD complex.
28614667	2	36	theme	activity-modifying	428:445	arg1	proteins					447:454	receptor activity-modifying proteins	419:454	receptor activity-modifying proteins (RAMPs)	419:462	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	2	36	theme	activity-modifying	428:445	arg1	RAMPs					457:461	RAMPs	457:461	RAMPs	457:461	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	6	37	contain	had	1231:1233	arg2	effect					1238:1243	no effect	1235:1243	no effect	1235:1243	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	37	contain	had	1231:1233	arg1	trimming					1179:1186	Endo H-catalyzed trimming	1162:1186	Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues	1162:1229	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	4	38	theme	peptide-binding	782:796	arg1	assays					798:803	fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays	708:803	fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays	708:803	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	5	39	theme	lower	876:880	arg1	affinity					890:897	∼10-fold lower peptide affinity	867:897	∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2)	867:1036	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	7	40	theme	receptor	1309:1316	arg1	complex					1332:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	Similar results were observed for an amylin receptor RAMP2-CTR ECD complex.
28614667	8	41	theme	single	1557:1562	arg1	responsible					1595:1605	responsible	1595:1605	responsible	1595:1605	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	8	41	theme	single	1557:1562	arg1	residue					1571:1577	a single GlcNAc residue	1555:1577	a single GlcNAc residue at CTR N130	1555:1589	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	8	42	theme	CTR	1406:1408	arg1	mutants					1426:1432	purified N → Q CTR ECD glycan site mutants	1391:1432	purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1391:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	8	43	theme	glycan	1414:1419	arg1	mutants					1426:1432	purified N → Q CTR ECD glycan site mutants	1391:1432	purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1391:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	0	44	theme	Extracellular	41:53	arg1	Receptor					86:93	the Human Calcitonin Receptor	65:93	the Human Calcitonin Receptor	65:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	0	44	theme	Extracellular	41:53	arg1	Domain					55:60	the Extracellular Domain	37:60	the Extracellular Domain of the Human Calcitonin Receptor	37:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	6	45	theme	peptide	1127:1133	arg1	affinity					1135:1142	peptide affinity	1127:1142	peptide affinity	1127:1142	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	8	46	theme	CTR	1582:1584	arg1	N130					1586:1589	CTR N130	1582:1589	CTR N130	1582:1589	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	10	47	theme	B	1909:1909	arg1	GPCR					1911:1914	a clinically relevant class B GPCR	1881:1914	a clinically relevant class B GPCR	1881:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	6	48	dep	decreased	1117:1125	arg1	whereas					1154:1160	whereas	1154:1160	whereas	1154:1160	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	4	49	theme	N-glycosylation	585:599	arg1	role					573:576	the role	569:576	the role of CTR N-glycosylation in hormone binding	569:618	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	10	50	theme	relevant	1894:1901	arg1	GPCR					1911:1914	a clinically relevant class B GPCR	1881:1914	a clinically relevant class B GPCR	1881:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	6	51	from	N130	1097:1100	arg1	ECD					1113:1115	the CTR ECD	1105:1115	the CTR ECD	1105:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	51	from	N130	1097:1100	arg1	removal					1058:1064	PNGase F-catalyzed removal	1039:1064	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD	1039:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	4	52	theme	hormone	604:610	arg1	binding					612:618	hormone binding	604:618	hormone binding	604:618	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	5	53	theme	N-Glycan-free	806:818	arg1	ECD					824:826	N-Glycan-free CTR ECD	806:826	N-Glycan-free CTR ECD produced in Escherichia coli	806:855	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	2	54	theme	blood	355:359	arg1	glucose					361:367	blood glucose	355:367	blood glucose	355:367	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	8	55	theme	peptide	1615:1621	arg1	enhancement					1632:1642	the peptide affinity enhancement	1611:1642	the peptide affinity enhancement	1611:1642	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	3	56	theme	diabetes	543:550	arg1	treatment					513:521	the treatment	509:521	the treatment of osteoporosis and diabetes	509:550	These receptors are targeted clinically for the treatment of osteoporosis and diabetes.
28614667	8	57	from	N130	1586:1589	arg1	responsible					1595:1605	responsible	1595:1605	responsible	1595:1605	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	8	57	from	N130	1586:1589	arg1	residue					1571:1577	a single GlcNAc residue	1555:1577	a single GlcNAc residue at CTR N130	1555:1589	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	3	58	theme	osteoporosis	526:537	arg1	treatment					513:521	the treatment	509:521	the treatment of osteoporosis and diabetes	509:550	These receptors are targeted clinically for the treatment of osteoporosis and diabetes.
28614667	1	59	dep	hormones	248:255	arg1	hormones					248:255	the peptide hormones calcitonin and amylin	236:277	the peptide hormones calcitonin and amylin	236:277	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	1	59	dep	hormones	248:255	arg1	amylin					272:277	amylin	272:277	amylin	272:277	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	1	59	dep	hormones	248:255	arg1	calcitonin					257:266	calcitonin	257:266	calcitonin	257:266	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	6	60	theme	H-catalyzed	1167:1177	arg1	trimming					1179:1186	Endo H-catalyzed trimming	1162:1186	Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues	1162:1229	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	4	61	theme	amylin	650:655	arg1	ECD					688:690	ECD	688:690	ECD	688:690	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	4	61	theme	amylin	650:655	arg1	domain					680:685	purified calcitonin and amylin receptor extracellular domain	626:685	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	5	62	theme	CTR	820:822	arg1	ECD					824:826	N-Glycan-free CTR ECD	806:826	N-Glycan-free CTR ECD produced in Escherichia coli	806:855	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	6	63	theme	peptide	1248:1254	arg1	binding					1256:1262	peptide binding	1248:1262	peptide binding	1248:1262	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	10	64	theme	important	1805:1813	arg1	role					1815:1818	an important role	1802:1818	an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR	1802:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	4	65	theme	extracellular	666:678	arg1	ECD					688:690	ECD	688:690	ECD	688:690	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	4	65	theme	extracellular	666:678	arg1	domain					680:685	purified calcitonin and amylin receptor extracellular domain	626:685	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	2	66	theme	bone	301:304	arg1	remodeling					306:315	bone remodeling	301:315	bone remodeling	301:315	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	5	67	theme	peptide	882:888	arg1	affinity					890:897	∼10-fold lower peptide affinity	867:897	∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2)	867:1036	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	9	68	theme	allosteric	1712:1721	arg1	mechanism					1723:1731	an allosteric mechanism	1709:1731	an allosteric mechanism	1709:1731	Molecular modeling suggested that this GlcNAc functions through an allosteric mechanism rather than by directly contacting the peptide.
28614667	8	69	theme	F	1455:1455	arg1	strategies					1478:1487	PNGase F and Endo H treatment strategies	1448:1487	PNGase F and Endo H treatment strategies	1448:1487	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	1	70	theme	protein-coupled	190:204	arg1	receptor					160:167	The calcitonin receptor	145:167	The calcitonin receptor (CTR)	145:173	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	1	70	theme	protein-coupled	190:204	arg1	receptor					206:213	a class B G protein-coupled receptor	178:213	a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin	178:277	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	8	71	theme	Endo	1461:1464	arg1	H					1466:1466	Endo H	1461:1466	Endo H	1461:1466	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	4	72	theme	calcitonin	635:644	arg1	ECD					688:690	ECD	688:690	ECD	688:690	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	4	72	theme	calcitonin	635:644	arg1	domain					680:685	purified calcitonin and amylin receptor extracellular domain	626:685	purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms	626:702	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	5	73	theme	complex	951:957	arg1	N-glycans					959:967	complex N-glycans	951:967	complex N-glycans	951:967	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	8	74	theme	treatment	1468:1476	arg1	strategies					1478:1487	PNGase F and Endo H treatment strategies	1448:1487	PNGase F and Endo H treatment strategies	1448:1487	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	2	75	dep	regulates	291:299	arg1	whereas					330:336	whereas	330:336	whereas	330:336	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	8	76	theme	mutants	1426:1432	arg1	affinities					1377:1386	peptide-binding affinities	1361:1386	peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1361:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	10	77	theme	hormone	1862:1868	arg1	binding					1870:1876	the peptide hormone binding	1850:1876	the peptide hormone binding of a clinically relevant class B GPCR	1850:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	6	78	theme	single	1208:1213	arg1	residues					1222:1229	single GlcNAc residues	1208:1229	single GlcNAc residues	1208:1229	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	4	79	theme	polarization/anisotropy	721:743	arg1	assays					798:803	fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays	708:803	fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays	708:803	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	1	80	theme	calcitonin	149:158	arg1	receptor					160:167	The calcitonin receptor	145:167	The calcitonin receptor (CTR)	145:173	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	1	80	theme	calcitonin	149:158	arg1	receptor					206:213	a class B G protein-coupled receptor	178:213	a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin	178:277	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	1	80	theme	calcitonin	149:158	arg1	CTR					170:172	CTR	170:172	CTR	170:172	The calcitonin receptor (CTR) is a class B G protein-coupled receptor that is activated by the peptide hormones calcitonin and amylin.
28614667	6	81	theme	PNGase	1039:1044	arg1	removal					1058:1064	PNGase F-catalyzed removal	1039:1064	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD	1039:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	6	82	theme	N-glycans	1195:1203	arg1	trimming					1179:1186	Endo H-catalyzed trimming	1162:1186	Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues	1162:1229	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	10	83	link	N-linked	1824:1831	arg1	glycosylation					1833:1845	N-linked glycosylation	1824:1845	N-linked glycosylation	1824:1845	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	0	84	theme	Calcitonin	75:84	arg1	Receptor					86:93	the Human Calcitonin Receptor	65:93	the Human Calcitonin Receptor	65:93	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	8	85	theme	glycan	1525:1530	arg1	species					1532:1538	the glycan species	1521:1538	the glycan species	1521:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	0	86	theme	Peptide	119:125	arg1	Affinity					135:142	Peptide Hormone Affinity	119:142	Peptide Hormone Affinity	119:142	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	10	87	from	role	1815:1818	arg1	binding					1870:1876	the peptide hormone binding	1850:1876	the peptide hormone binding of a clinically relevant class B GPCR	1850:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	8	88	theme	peptide-binding	1361:1375	arg1	affinities					1377:1386	peptide-binding affinities	1361:1386	peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1361:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	4	89	from	role	573:576	arg1	binding					612:618	hormone binding	604:618	hormone binding	604:618	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	7	90	theme	RAMP2-CTR	1318:1326	arg1	complex					1332:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	Similar results were observed for an amylin receptor RAMP2-CTR ECD complex.
28614667	4	91	theme	isothermal	749:758	arg1	calorimetry					770:780	isothermal titration calorimetry	749:780	isothermal titration calorimetry	749:780	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	2	92	theme	food	373:376	arg1	intake					378:383	food intake	373:383	food intake	373:383	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	8	93	dep	strategies	1478:1487	arg1	define					1514:1519	define	1514:1519	to define the glycan species	1511:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	5	94	theme	GnTI-	984:988	arg1	cells					990:994	HEK293S GnTI- cells	976:994	HEK293S GnTI- cells	976:994	N-Glycan-free CTR ECD produced in Escherichia coli exhibited ∼10-fold lower peptide affinity than CTR ECD produced in HEK293T cells, which yield complex N-glycans, or in HEK293S GnTI- cells, which yield core N-glycans (Man5GlcNAc2).
28614667	7	95	theme	amylin	1302:1307	arg1	complex					1332:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	an amylin receptor RAMP2-CTR ECD complex	1299:1338	Similar results were observed for an amylin receptor RAMP2-CTR ECD complex.
28614667	2	96	theme	receptor	419:426	arg1	proteins					447:454	receptor activity-modifying proteins	419:454	receptor activity-modifying proteins (RAMPs)	419:462	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	2	96	theme	receptor	419:426	arg1	RAMPs					457:461	RAMPs	457:461	RAMPs	457:461	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	8	97	theme	GlcNAc	1564:1569	arg1	responsible					1595:1605	responsible	1595:1605	responsible	1595:1605	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	8	97	theme	GlcNAc	1564:1569	arg1	residue					1571:1577	a single GlcNAc residue	1555:1577	a single GlcNAc residue at CTR N130	1555:1589	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	4	98	theme	calorimetry	770:780	arg1	assays					798:803	fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays	708:803	fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays	708:803	Here, we define the role of CTR N-glycosylation in hormone binding using purified calcitonin and amylin receptor extracellular domain (ECD) glycoforms and fluorescence polarization/anisotropy and isothermal titration calorimetry peptide-binding assays.
28614667	9	99	dep	functions	1691:1699	arg1	contacting					1757:1766	contacting	1757:1766	directly contacting the peptide	1748:1778	Molecular modeling suggested that this GlcNAc functions through an allosteric mechanism rather than by directly contacting the peptide.
28614667	0	100	gly	N-Glycosylation	0:14	arg1	Asparagine					19:28	Asparagine 130	19:32	Asparagine 130	19:32	N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.
28614667	6	101	theme	N-glycans	1069:1077	arg1	removal					1058:1064	PNGase F-catalyzed removal	1039:1064	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD	1039:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
28614667	8	102	theme	Q	1404:1404	arg1	mutants					1426:1432	purified N → Q CTR ECD glycan site mutants	1391:1432	purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1391:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	10	103	theme	GPCR	1911:1914	arg1	binding					1870:1876	the peptide hormone binding	1850:1876	the peptide hormone binding of a clinically relevant class B GPCR	1850:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	8	104	theme	ECD	1410:1412	arg1	mutants					1426:1432	purified N → Q CTR ECD glycan site mutants	1391:1432	purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1391:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	7	105	theme	Similar	1265:1271	arg1	results					1273:1279	Similar results	1265:1279	Similar results	1265:1279	Similar results were observed for an amylin receptor RAMP2-CTR ECD complex.
28614667	10	106	theme	class	1903:1907	arg1	GPCR					1911:1914	a clinically relevant class B GPCR	1881:1914	a clinically relevant class B GPCR	1881:1914	These results reveal an important role for N-linked glycosylation in the peptide hormone binding of a clinically relevant class B GPCR.
28614667	8	107	theme	site	1421:1424	arg1	mutants					1426:1432	purified N → Q CTR ECD glycan site mutants	1391:1432	purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species	1391:1538	Characterization of peptide-binding affinities of purified N → Q CTR ECD glycan site mutants combined with PNGase F and Endo H treatment strategies and mass spectrometry to define the glycan species indicated that a single GlcNAc residue at CTR N130 was responsible for the peptide affinity enhancement.
28614667	2	108	from	CTR	399:401	arg1	complex					406:412	complex	406:412	complex with receptor activity-modifying proteins (RAMPs)	406:462	Calcitonin regulates bone remodeling through CTR, whereas amylin regulates blood glucose and food intake by activating CTR in complex with receptor activity-modifying proteins (RAMPs).
28614667	6	109	theme	CTR	1109:1111	arg1	ECD					1113:1115	the CTR ECD	1105:1115	the CTR ECD	1105:1115	PNGase F-catalyzed removal of N-glycans at N73, N125, and N130 in the CTR ECD decreased peptide affinity ∼10-fold, whereas Endo H-catalyzed trimming of the N-glycans to single GlcNAc residues had no effect on peptide binding.
30016717	13	0	dep	organization	2712:2723	arg1	the					2708:2710	the	2708:2710	the	2708:2710	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	10	1	theme	O-GlcNAcylation	2012:2026	arg1	role					2004:2007	the role	2000:2007	the role of O-GlcNAcylation on a given protein	2000:2045	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	3	2	theme	unmodified	554:563	arg1	proteins					565:572	unmodified proteins	554:572	unmodified proteins	554:572	Despite the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation, it remains a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones.
30016717	8	3	from	role	1252:1255	arg1	interaction					1323:1333	interaction	1323:1333	interaction between key structural protein	1323:1364	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	8	3	from	role	1252:1255	arg1	modulation					1283:1292	the modulation	1279:1292	the modulation of sarcomere morphometry	1279:1317	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	4	4	theme	click	637:641	arg1	approach					653:660	a click chemistry approach	635:660	a click chemistry approach	635:660	Based on a click chemistry approach, O-GlcNAcylated proteins were labelled with azido-GalNAc and coupled to agarose beads.
30016717	9	5	theme	interaction	1521:1531	arg1	domains					1533:1539	protein-protein interaction domains	1505:1539	protein-protein interaction domains	1505:1539	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	8	6	theme	recent	1245:1250	arg1	role					1252:1255	the recent role	1241:1255	the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein	1241:1364	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	6	7	theme	O-GlcNAc	962:969	arg1	sites					971:975	O-GlcNAc sites	962:975	O-GlcNAc sites	962:975	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	12	8	contain	containing	2238:2247	arg1	peptides					2229:2236	620 peptides	2225:2236	620 peptides containing one or more O-GlcNAc sites	2225:2274	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	12	8	contain	containing	2238:2247	arg2	sites					2270:2274	one or more O-GlcNAc sites	2249:2274	one or more O-GlcNAc sites	2249:2274	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	12	9	theme	peptides	2229:2236	arg1	total					2216:2220	A total	2214:2220	A total of 620 peptides containing one or more O-GlcNAc sites	2214:2274	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	11	10	theme	muscle	2114:2119	arg1	cells					2121:2125	skeletal muscle cells	2105:2125	skeletal muscle cells proteome with click chemistry	2105:2155	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	13	11	theme	protein-protein	2621:2635	arg1	domains					2649:2655	protein-protein interaction domains	2621:2655	protein-protein interaction domains	2621:2655	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	10	12	theme	localization	1893:1904	arg1	ignorance					1862:1870	the ignorance	1858:1870	the ignorance of the O-GlcNAc site localization	1858:1904	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	1	13	theme	numerous	224:231	arg1	aspects					233:239	numerous aspects	224:239	numerous aspects of cellular processes	224:261	The O-linked-N-acetyl-d-glucosaminylation (O-GlcNAcylation) modulates numerous aspects of cellular processes.
30016717	8	14	theme	structural	1347:1356	arg1	protein					1358:1364	key structural protein	1343:1364	key structural protein	1343:1364	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	10	15	theme	atypical	1705:1712	arg1	O-GlcNAcylation					1683:1697	O-GlcNAcylation	1683:1697	O-GlcNAcylation	1683:1697	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	10	15	theme	atypical	1705:1712	arg1	SIGNIFICANCE					1669:1680	SIGNIFICANCE	1669:1680	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.	1669:2046	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	10	15	theme	atypical	1705:1712	arg1	glycosylation					1714:1726	an atypical glycosylation	1702:1726	an atypical glycosylation involved in the regulation of almost all if not all cellular processes	1702:1797	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	0	16	theme	skeletal	122:129	arg1	proteins					144:151	skeletal muscle cells proteins	122:151	skeletal muscle cells proteins	122:151	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	10	17	theme	O-GlcNAc	1879:1886	arg1	localization					1893:1904	the O-GlcNAc site localization	1875:1904	the O-GlcNAc site localization	1875:1904	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	13	18	theme	myofibrils	2783:2792	arg1	involvement					2674:2684	the involvement	2670:2684	the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils	2670:2792	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	10	19	theme	all	1765:1767	arg1	regulation					1744:1753	the regulation	1740:1753	the regulation of almost all if not all cellular processes	1740:1797	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	0	20	theme	cells	138:142	arg1	proteins					144:151	skeletal muscle cells proteins	122:151	skeletal muscle cells proteins	122:151	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	11	21	theme	click	2141:2145	arg1	chemistry					2147:2155	click chemistry	2141:2155	click chemistry	2141:2155	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	1	22	theme	processes	253:261	arg1	aspects					233:239	numerous aspects	224:239	numerous aspects of cellular processes	224:261	The O-linked-N-acetyl-d-glucosaminylation (O-GlcNAcylation) modulates numerous aspects of cellular processes.
30016717	8	23	theme	sarcomere	1297:1305	arg1	morphometry					1307:1317	sarcomere morphometry	1297:1317	sarcomere morphometry	1297:1317	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	11	24	theme	priori	2192:2197	arg1	consideration					2199:2211	an a priori consideration	2187:2211	an a priori consideration	2187:2211	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	13	25	from	involvement	2674:2684	arg1	organization					2712:2723	organization	2712:2723	organization	2712:2723	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	13	25	from	involvement	2674:2684	arg1	extent					2772:2777	larger extent	2765:2777	larger extent	2765:2777	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	9	26	gly	O-GlcNAcylation	1558:1572	arg1	reorganization					1625:1638	reorganization	1625:1638	reorganization	1625:1638	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	9	26	gly	O-GlcNAcylation	1558:1572	arg1	organization					1608:1619	organization	1608:1619	organization	1608:1619	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	5	27	theme	intensive	812:820	arg1	fractionation					822:834	an intensive fractionation	809:834	an intensive fractionation prior to azide-alkyne click chemistry	809:872	The proteome extracted from C2C12 myotubes was submitted to an intensive fractionation prior to azide-alkyne click chemistry.
30016717	11	28	theme	extensive	2078:2086	arg1	fractionation					2088:2100	extensive fractionation	2078:2100	extensive fractionation of skeletal muscle cells proteome with click chemistry	2078:2155	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	0	29	theme	mass	67:70	arg1	spectrometry					72:83	mass spectrometry	67:83	mass spectrometry	67:83	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	9	30	theme	sarcomere	1643:1651	arg1	reorganization					1625:1638	reorganization	1625:1638	reorganization	1625:1638	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	9	30	theme	sarcomere	1643:1651	arg1	organization					1608:1619	organization	1608:1619	organization	1608:1619	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	8	31	theme	skeletal	1426:1433	arg1	cells					1442:1446	skeletal muscle cells	1426:1446	skeletal muscle cells	1426:1446	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	9	32	theme	myofibrils	1657:1666	arg1	reorganization					1625:1638	reorganization	1625:1638	reorganization	1625:1638	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	9	32	theme	myofibrils	1657:1666	arg1	organization					1608:1619	organization	1608:1619	organization	1608:1619	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	6	33	theme	peptides	1049:1056	arg1	identification					1027:1040	the identification	1023:1040	the identification of 620 peptides containing one or more O-GlcNAc sites	1023:1094	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	8	34	theme	cells	1442:1446	arg1	cytoarchitecture					1406:1421	the cytoarchitecture	1402:1421	the cytoarchitecture of skeletal muscle cells	1402:1446	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	0	35	theme	azide-alkyne	33:44	arg1	chemistry					53:61	(azide-alkyne) click chemistry	32:61	(azide-alkyne) click chemistry	32:61	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	13	36	theme	cytoarchitecture	2546:2561	arg1	modulation					2522:2531	the modulation	2518:2531	the modulation of sarcomere cytoarchitecture	2518:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	10	37	from	role	2004:2007	arg1	protein					2039:2045	a given protein	2031:2045	a given protein	2031:2045	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	9	38	located	located	1492:1498	arg1	particular					1452:1461	particular	1452:1461	particular	1452:1461	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	9	38	located	located	1492:1498	arg2	sites					1481:1485	several O-GlcNAc sites	1464:1485	several O-GlcNAc sites	1464:1485	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	0	39	theme	O-GlcNAcylation	0:14	arg1	site					16:19	O-GlcNAcylation site	0:19	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry	0:83	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	13	40	theme	O-GlcNAcylation	2499:2513	arg1	role					2491:2494	the role	2487:2494	the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture	2487:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	12	41	theme	them	2319:2322	arg1	several					2308:2314	several	2308:2314	several	2308:2314	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	13	42	from	role	2491:2494	arg1	modulation					2522:2531	the modulation	2518:2531	the modulation of sarcomere cytoarchitecture	2518:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	3	43	theme	high	513:516	arg1	challenge					518:526	a high challenge	511:526	a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones	511:623	Despite the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation, it remains a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones.
30016717	11	44	theme	skeletal	2105:2112	arg1	cells					2121:2125	skeletal muscle cells	2105:2125	skeletal muscle cells proteome with click chemistry	2105:2155	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	5	45	theme	azide-alkyne	845:856	arg1	chemistry					864:872	azide-alkyne click chemistry	845:872	azide-alkyne click chemistry	845:872	The proteome extracted from C2C12 myotubes was submitted to an intensive fractionation prior to azide-alkyne click chemistry.
30016717	3	46	theme	major	536:540	arg1	reason					542:547	the major reason	532:547	the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones	532:623	Despite the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation, it remains a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones.
30016717	13	47	theme	O-GlcNAcylation	2689:2703	arg1	involvement					2674:2684	the involvement	2670:2684	the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils	2670:2792	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	6	48	theme	chemistry	919:927	arg1	combination					880:890	This combination	875:890	This combination of fractionation and click chemistry	875:927	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	6	48	theme	chemistry	919:927	arg1	methodology					943:953	a powerful methodology	932:953	a powerful methodology to map O-GlcNAc sites	932:975	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	10	49	theme	precise	1808:1814	arg1	role					1816:1819	its precise role	1804:1819	its precise role	1804:1819	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	9	50	theme	several	1464:1470	arg1	sites					1481:1485	several O-GlcNAc sites	1464:1485	several O-GlcNAc sites	1464:1485	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	4	51	theme	agarose	734:740	arg1	beads					742:746	agarose beads	734:746	agarose beads	734:746	Based on a click chemistry approach, O-GlcNAcylated proteins were labelled with azido-GalNAc and coupled to agarose beads.
30016717	4	52	theme	chemistry	643:651	arg1	approach					653:660	a click chemistry approach	635:660	a click chemistry approach	635:660	Based on a click chemistry approach, O-GlcNAcylated proteins were labelled with azido-GalNAc and coupled to agarose beads.
30016717	13	53	from	proteins	2444:2451	arg1	view					2456:2459	view	2456:2459	view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture	2456:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	12	54	theme	620	2225:2227	arg1	peptides					2229:2236	620 peptides	2225:2236	620 peptides containing one or more O-GlcNAc sites	2225:2274	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	5	55	theme	click	858:862	arg1	chemistry					864:872	azide-alkyne click chemistry	845:872	azide-alkyne click chemistry	845:872	The proteome extracted from C2C12 myotubes was submitted to an intensive fractionation prior to azide-alkyne click chemistry.
30016717	13	56	theme	recent	2464:2469	arg1	data					2471:2474	recent data	2464:2474	recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture	2464:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	13	57	theme	interaction	2637:2647	arg1	domains					2649:2655	protein-protein interaction domains	2621:2655	protein-protein interaction domains	2621:2655	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	10	58	theme	given	2033:2037	arg1	protein					2039:2045	a given protein	2031:2045	a given protein	2031:2045	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	7	59	theme	protein	1175:1181	arg1	modification					1183:1194	protein modification	1175:1194	protein modification	1175:1194	We localized O-GlcNAc sites on proteins involved in signalling pathways or in protein modification, as well as structural proteins.
30016717	11	60	theme	cells	2121:2125	arg1	fractionation					2088:2100	extensive fractionation	2078:2100	extensive fractionation of skeletal muscle cells proteome with click chemistry	2078:2155	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	9	61	theme	protein-protein	1505:1519	arg1	domains					1533:1539	protein-protein interaction domains	1505:1539	protein-protein interaction domains	1505:1539	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	10	62	theme	ignorance	1862:1870	arg1	obscure					1839:1845	obscure	1839:1845	obscure	1839:1845	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	8	63	theme	morphometry	1307:1317	arg1	interaction					1323:1333	interaction	1323:1333	interaction between key structural protein	1323:1364	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	8	63	theme	morphometry	1307:1317	arg1	modulation					1283:1292	the modulation	1279:1292	the modulation of sarcomere morphometry	1279:1317	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	5	64	theme	prior	836:840	arg1	fractionation					822:834	an intensive fractionation	809:834	an intensive fractionation prior to azide-alkyne click chemistry	809:872	The proteome extracted from C2C12 myotubes was submitted to an intensive fractionation prior to azide-alkyne click chemistry.
30016717	7	65	theme	signalling	1149:1158	arg1	pathways					1160:1167	signalling pathways	1149:1167	signalling pathways	1149:1167	We localized O-GlcNAc sites on proteins involved in signalling pathways or in protein modification, as well as structural proteins.
30016717	13	66	theme	structural	2433:2442	arg1	proteins					2444:2451	structural proteins	2433:2451	structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture	2433:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	6	67	theme	620	1045:1047	arg1	peptides					1049:1056	620 peptides	1045:1056	620 peptides containing one or more O-GlcNAc sites	1045:1094	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	0	68	theme	muscle	131:136	arg1	proteins					144:151	skeletal muscle cells proteins	122:151	skeletal muscle cells proteins	122:151	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	10	69	theme	site	1888:1891	arg1	localization					1893:1904	the O-GlcNAc site localization	1875:1904	the O-GlcNAc site localization	1875:1904	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	8	70	theme	O-GlcNAcylation	1260:1274	arg1	role					1252:1255	the recent role	1241:1255	the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein	1241:1364	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	8	71	theme	key	1343:1345	arg1	protein					1358:1364	key structural protein	1343:1364	key structural protein	1343:1364	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	0	72	theme	proteins	144:151	arg1	fractionation					105:117	intensive fractionation	95:117	intensive fractionation of skeletal muscle cells proteins	95:151	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	1	73	theme	cellular	244:251	arg1	processes					253:261	cellular processes	244:261	cellular processes	244:261	The O-linked-N-acetyl-d-glucosaminylation (O-GlcNAcylation) modulates numerous aspects of cellular processes.
30016717	11	74	theme	O-GlcNAc	2164:2171	arg1	sites					2173:2177	O-GlcNAc sites	2164:2177	O-GlcNAc sites	2164:2177	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	7	75	theme	O-GlcNAc	1110:1117	arg1	sites					1119:1123	O-GlcNAc sites	1110:1123	O-GlcNAc sites	1110:1123	We localized O-GlcNAc sites on proteins involved in signalling pathways or in protein modification, as well as structural proteins.
30016717	11	76	theme	a	2190:2190	arg1	consideration					2199:2211	an a priori consideration	2187:2211	an a priori consideration	2187:2211	For this purpose, we combined extensive fractionation of skeletal muscle cells proteome with click chemistry to map O-GlcNAc sites without an a priori consideration.
30016717	6	77	theme	O-GlcNAc	1081:1088	arg1	sites					1090:1094	one or more O-GlcNAc sites	1069:1094	one or more O-GlcNAc sites	1069:1094	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	2	78	dep	dynamic	315:321	arg1	reversible					324:333	reversible	324:333	reversible	324:333	Akin to phosphorylation, O-GlcNAcylation is highly dynamic, reversible, and responds rapidly to extracellular demand.
30016717	13	79	theme	larger	2765:2770	arg1	extent					2772:2777	larger extent	2765:2777	larger extent	2765:2777	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	9	80	from	particular	1452:1461	arg1	located					1492:1498	located	1492:1498	located	1492:1498	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	12	81	theme	signalling	2393:2402	arg1	pathways					2404:2411	signalling pathways	2393:2411	signalling pathways	2393:2411	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	0	82	theme	intensive	95:103	arg1	fractionation					105:117	intensive fractionation	95:117	intensive fractionation of skeletal muscle cells proteins	95:151	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	3	83	theme	O-GlcNAcylated	605:618	arg1	ones					620:623	the O-GlcNAcylated ones	601:623	the O-GlcNAcylated ones	601:623	Despite the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation, it remains a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones.
30016717	9	84	dep	organization	1608:1619	arg1	the					1604:1606	the	1604:1606	the	1604:1606	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	13	85	theme	sarcomere	2747:2755	arg1	organization					2712:2723	organization	2712:2723	organization	2712:2723	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	13	86	theme	sarcomere	2536:2544	arg1	cytoarchitecture					2546:2561	sarcomere cytoarchitecture	2536:2561	sarcomere cytoarchitecture	2536:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	3	87	theme	absolute	394:401	arg1	necessity					403:411	the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation	390:497	the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation	390:497	Despite the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation, it remains a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones.
30016717	12	88	theme	particular	2361:2370	arg1	proteins					2372:2379	particular proteins	2361:2379	particular proteins involved in signalling pathways	2361:2411	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	8	89	theme	muscle	1435:1440	arg1	cells					1442:1446	skeletal muscle cells	1426:1446	skeletal muscle cells	1426:1446	Considering the recent role of O-GlcNAcylation in the modulation of sarcomere morphometry and interaction between key structural protein, we focused on proteins involved in the cytoarchitecture of skeletal muscle cells.
30016717	13	90	theme	O-GlcNAc	2589:2596	arg1	sites					2598:2602	the O-GlcNAc sites	2585:2602	the O-GlcNAc sites	2585:2602	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	6	91	contain	containing	1058:1067	arg1	peptides					1049:1056	620 peptides	1045:1056	620 peptides containing one or more O-GlcNAc sites	1045:1094	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	6	91	contain	containing	1058:1067	arg2	sites					1090:1094	one or more O-GlcNAc sites	1069:1094	one or more O-GlcNAc sites	1069:1094	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	3	92	theme	O-GlcNAcylation	483:497	arg1	role					475:478	the role	471:478	the role of O-GlcNAcylation	471:497	Despite the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation, it remains a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones.
30016717	3	93	theme	post-translational	426:443	arg1	sites					445:449	post-translational sites	426:449	post-translational sites	426:449	Despite the absolute necessity to determine post-translational sites to fully understand the role of O-GlcNAcylation, it remains a high challenge for the major reason that unmodified proteins are in excess comparing to the O-GlcNAcylated ones.
30016717	12	94	theme	expressed	2338:2346	arg1	proteins					2348:2355	low expressed proteins	2334:2355	low expressed proteins	2334:2355	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	7	95	theme	structural	1208:1217	arg1	proteins					1219:1226	structural proteins	1208:1226	structural proteins	1208:1226	We localized O-GlcNAc sites on proteins involved in signalling pathways or in protein modification, as well as structural proteins.
30016717	9	96	from	located	1492:1498	arg1	particular					1452:1461	particular	1452:1461	particular	1452:1461	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	6	97	theme	powerful	934:941	arg1	combination					880:890	This combination	875:890	This combination of fractionation and click chemistry	875:927	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	6	97	theme	powerful	934:941	arg1	methodology					943:953	a powerful methodology	932:953	a powerful methodology to map O-GlcNAc sites	932:975	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	13	98	theme	data	2471:2474	arg1	view					2456:2459	view	2456:2459	view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture	2456:2561	We also focused on structural proteins in view of recent data supporting the role of O-GlcNAcylation in the modulation of sarcomere cytoarchitecture; importantly, some of the O-GlcNAc sites were mapped into protein-protein interaction domains, reinforcing the involvement of O-GlcNAcylation in the organization and reorganization of sarcomere, and in larger extent, of myofibrils.
30016717	10	99	theme	O-GlcNAcylated	1959:1972	arg1	sites					1974:1978	the O-GlcNAcylated sites	1955:1978	the O-GlcNAcylated sites	1955:1978	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	10	100	theme	cellular	1780:1787	arg1	processes					1789:1797	not all cellular processes	1772:1797	not all cellular processes	1772:1797	SIGNIFICANCE: O-GlcNAcylation is an atypical glycosylation involved in the regulation of almost all if not all cellular processes, but its precise role remains sometimes obscure because of the ignorance of the O-GlcNAc site localization; thus, it remains indispensable to precisely map the O-GlcNAcylated sites to fully understand the role of O-GlcNAcylation on a given protein.
30016717	0	101	theme	click	47:51	arg1	chemistry					53:61	(azide-alkyne) click chemistry	32:61	(azide-alkyne) click chemistry	32:61	O-GlcNAcylation site mapping by (azide-alkyne) click chemistry and mass spectrometry following intensive fractionation of skeletal muscle cells proteins.
30016717	5	102	theme	C2C12	777:781	arg1	myotubes					783:790	C2C12 myotubes	777:790	C2C12 myotubes	777:790	The proteome extracted from C2C12 myotubes was submitted to an intensive fractionation prior to azide-alkyne click chemistry.
30016717	6	103	theme	click	913:917	arg1	chemistry					919:927	click chemistry	913:927	click chemistry	913:927	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	12	104	theme	low	2334:2336	arg1	proteins					2348:2355	low expressed proteins	2334:2355	low expressed proteins	2334:2355	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
30016717	2	105	theme	extracellular	360:372	arg1	demand					374:379	extracellular demand	360:379	extracellular demand	360:379	Akin to phosphorylation, O-GlcNAcylation is highly dynamic, reversible, and responds rapidly to extracellular demand.
30016717	9	106	theme	O-GlcNAc	1472:1479	arg1	sites					1481:1485	several O-GlcNAc sites	1464:1485	several O-GlcNAc sites	1464:1485	In particular, several O-GlcNAc sites were located into protein-protein interaction domains, suggesting that O-GlcNAcylation could be strongly involved in the organization and reorganization of sarcomere and myofibrils.
30016717	6	107	theme	fractionation	895:907	arg1	combination					880:890	This combination	875:890	This combination of fractionation and click chemistry	875:927	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	6	107	theme	fractionation	895:907	arg1	methodology					943:953	a powerful methodology	932:953	a powerful methodology to map O-GlcNAc sites	932:975	This combination of fractionation and click chemistry is a powerful methodology to map O-GlcNAc sites; indeed, 342 proteins were identified through the identification of 620 peptides containing one or more O-GlcNAc sites.
30016717	4	108	theme	O-GlcNAcylated	663:676	arg1	proteins					678:685	O-GlcNAcylated proteins	663:685	O-GlcNAcylated proteins	663:685	Based on a click chemistry approach, O-GlcNAcylated proteins were labelled with azido-GalNAc and coupled to agarose beads.
30016717	12	109	theme	O-GlcNAc	2261:2268	arg1	sites					2270:2274	one or more O-GlcNAc sites	2249:2274	one or more O-GlcNAc sites	2249:2274	A total of 620 peptides containing one or more O-GlcNAc sites were identified; interestingly, several of them belong to low expressed proteins, in particular proteins involved in signalling pathways.
29526322	7	0	theme	NCX3	875:878	arg1	Glycosylation					858:870	Glycosylation	858:870	Glycosylation of NCX3 at the N45 site	858:894	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	8	1	theme	cells	1171:1175	arg1	arrest					1161:1166	an arrest	1158:1166	an arrest of cells in the G0/G1 phase of the cell cycle	1158:1212	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	1	2	theme	envelope	232:239	arg1	membrane					208:215	the inner membrane	198:215	the inner membrane of the nuclear envelope	198:239	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	1	2	theme	envelope	232:239	arg1	membrane					188:195	the plasma membrane	177:195	the plasma membrane	177:195	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	10	3	dep	results	1387:1393	arg1	confirmed					1441:1449	confirmed	1441:1449	confirmed endogenously in SH-SY5Y cells	1441:1479	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	10	3	dep	results	1387:1393	arg1	obtained					1396:1403	obtained	1396:1403	obtained in transfected HEK293T and HeLa	1396:1435	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	6	4	theme	S	770:770	arg1	phase					778:782	S and M phase	770:782	phase	778:782	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	4	5	theme	subcellular	544:554	arg1	localization					556:567	the subcellular localization	540:567	the subcellular localization of the NCX subtype 3 (NCX3)	540:595	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	7	6	theme	plasma	1051:1056	arg1	membrane					1058:1065	the plasma membrane	1047:1065	the plasma membrane	1047:1065	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	10	7	theme	signaling	1524:1532	arg1	toolkit					1534:1540	a dynamic Ca2+ signaling toolkit	1509:1540	a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle	1509:1625	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	8	8	theme	cell	1203:1206	arg1	cycle					1208:1212	the cell cycle	1199:1212	the cell cycle	1199:1212	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	10	9	theme	Ca2+	1519:1522	arg1	toolkit					1534:1540	a dynamic Ca2+ signaling toolkit	1509:1540	a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle	1509:1625	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	9	10	theme	de-glycosylated	1255:1269	arg1	NCX3					1271:1274	de-glycosylated NCX3	1255:1274	de-glycosylated NCX3	1255:1274	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	4	11	from	localization	556:567	arg1	cycle					624:628	the cell cycle	615:628	the cell cycle	615:628	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	10	12	theme	dynamic	1511:1517	arg1	toolkit					1534:1540	a dynamic Ca2+ signaling toolkit	1509:1540	a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle	1509:1625	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	2	13	theme	unique	350:355	arg1	proteins					361:368	unique NCX proteins	350:368	unique NCX proteins	350:368	In humans, three genes have been identified, encoding unique NCX proteins.
29526322	7	14	gly	Glycosylation	858:870	arg2	site					891:894	the N45 site	883:894	the N45 site	883:894	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	7	14	gly	Glycosylation	858:870	arg1	NCX3					875:878	NCX3	875:878	NCX3	875:878	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	8	15	theme	G0/G1	1184:1188	arg1	phase					1190:1194	the G0/G1 phase	1180:1194	the G0/G1 phase of the cell cycle	1180:1212	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	7	16	theme	NCX3	1032:1035	arg1	translocation					1015:1027	the translocation	1011:1027	the translocation of NCX3 to either the plasma membrane or the membrane of the ER	1011:1091	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	1	17	theme	Na+/Ca2+	99:106	arg1	exchanger					108:116	The Na+/Ca2+ exchanger	95:116	The Na+/Ca2+ exchanger (NCX)	95:122	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	1	17	theme	Na+/Ca2+	99:106	arg1	antiporter					138:147	a membrane antiporter	127:147	a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER)	127:293	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	1	17	theme	Na+/Ca2+	99:106	arg1	NCX					119:121	NCX	119:121	NCX	119:121	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	4	18	from	impact	605:610	arg1	cycle					624:628	the cell cycle	615:628	the cell cycle	615:628	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	4	19	theme	cell	619:622	arg1	cycle					624:628	the cell cycle	615:628	the cell cycle	615:628	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	10	20	theme	cell	1616:1619	arg1	cycle					1621:1625	the cell cycle	1612:1625	the cell cycle	1612:1625	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	8	21	from	arrest	1161:1166	arg1	phase					1190:1194	the G0/G1 phase	1180:1194	the G0/G1 phase of the cell cycle	1180:1212	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	1	22	theme	plasma	181:186	arg1	membrane					208:215	the inner membrane	198:215	the inner membrane of the nuclear envelope	198:239	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	1	22	theme	plasma	181:186	arg1	membrane					188:195	the plasma membrane	177:195	the plasma membrane	177:195	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	0	23	theme	exchanger	38:46	arg1	localization					63:74	sodium-calcium exchanger 3 sub-cellular localization	23:74	sodium-calcium exchanger 3 sub-cellular localization	23:74	Glycosylation controls sodium-calcium exchanger 3 sub-cellular localization during cell cycle.
29526322	9	24	gly	de-glycosylated	1255:1269	arg1	NCX3					1271:1274	de-glycosylated NCX3	1255:1274	de-glycosylated NCX3	1255:1274	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	7	25	theme	plasma	942:947	arg1	membrane					949:956	the plasma membrane	938:956	the plasma membrane	938:956	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	10	26	theme	NCX3	1555:1558	arg1	localization					1573:1584	the NCX3 sub-cellular localization	1551:1584	the NCX3 sub-cellular localization	1551:1584	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	8	27	theme	cycle	1208:1212	arg1	phase					1190:1194	the G0/G1 phase	1180:1194	the G0/G1 phase of the cell cycle	1180:1212	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	3	28	theme	sub-cellular	411:422	arg1	localization					424:435	the NCX's sub-cellular localization	401:435	the NCX's sub-cellular localization	401:435	Although extensively studied, the NCX's sub-cellular localization and mechanisms regulating the activity of different subtypes are still ambiguous.
29526322	0	29	theme	sodium-calcium	23:36	arg1	exchanger					38:46	sodium-calcium exchanger 3	23:48	sodium-calcium exchanger 3 sub-cellular localization	23:74	Glycosylation controls sodium-calcium exchanger 3 sub-cellular localization during cell cycle.
29526322	10	30	with	synchrony	1597:1605	arg1	cycle					1621:1625	the cell cycle	1612:1625	the cell cycle	1612:1625	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	7	31	theme	ER	1090:1091	arg1	membrane					1058:1065	the plasma membrane	1047:1065	the plasma membrane	1047:1065	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	7	31	theme	ER	1090:1091	arg1	membrane					1074:1081	the membrane	1070:1081	the membrane of the ER	1070:1091	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	9	32	theme	calcium	1333:1339	arg1	Ca2+					1347:1350	Ca2+	1347:1350	Ca2+	1347:1350	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	9	32	theme	calcium	1333:1339	arg1	ions					1341:1344	calcium ions	1333:1344	calcium ions (Ca2+) from the cytosol to the ER	1333:1378	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	7	33	from	site	891:894	arg1	Glycosylation					858:870	Glycosylation	858:870	Glycosylation of NCX3 at the N45 site	858:894	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	0	34	theme	sub-cellular	50:61	arg1	localization					63:74	sodium-calcium exchanger 3 sub-cellular localization	23:74	sodium-calcium exchanger 3 sub-cellular localization	23:74	Glycosylation controls sodium-calcium exchanger 3 sub-cellular localization during cell cycle.
29526322	1	35	theme	endoplasmic	268:278	arg1	ER					291:292	ER	291:292	ER	291:292	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	1	35	theme	endoplasmic	268:278	arg1	reticulum					280:288	the endoplasmic reticulum	264:288	the endoplasmic reticulum (ER)	264:293	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	6	36	theme	M	776:776	arg1	phase					778:782	S and M phase	770:782	phase	778:782	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	6	37	from	NCX3	735:738	arg1	membrane					754:761	the plasma membrane	743:761	the plasma membrane	743:761	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	6	37	from	NCX3	735:738	arg1	membrane					818:825	the ER membrane	811:825	the ER membrane	811:825	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	8	38	theme	deficient	1129:1137	arg1	mutant					1144:1149	an N-glycosylation deficient NCX3 mutant	1110:1149	an N-glycosylation deficient NCX3 mutant	1110:1149	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	9	39	theme	NCX3	1271:1274	arg1	accumulation					1239:1250	accumulation	1239:1250	accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER	1239:1378	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	1	40	theme	reticulum	280:288	arg1	membrane					252:259	the membrane	248:259	the membrane of the endoplasmic reticulum (ER)	248:293	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	9	41	from	accumulation	1239:1250	arg1	cytosol					1283:1289	the cytosol	1279:1289	the cytosol (that is in the ER)	1279:1309	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	3	42	dep	studied	392:398	arg1	Although					371:378	Although	371:378	Although	371:378	Although extensively studied, the NCX's sub-cellular localization and mechanisms regulating the activity of different subtypes are still ambiguous.
29526322	1	43	theme	inner	202:206	arg1	membrane					208:215	the inner membrane	198:215	the inner membrane of the nuclear envelope	198:239	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	1	43	theme	inner	202:206	arg1	membrane					188:195	the plasma membrane	177:195	the plasma membrane	177:195	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	7	44	theme	on-off	993:998	arg1	switch					1000:1005	an on-off switch	990:1005	an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER	990:1091	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	7	44	theme	on-off	993:998	arg1	site					971:974	the N45 site	963:974	the N45 site	963:974	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	10	45	theme	transfected	1408:1418	arg1	HEK293T					1420:1426	HEK293T	1420:1426	HEK293T	1420:1426	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	5	46	theme	cell	690:693	arg1	cycle					695:699	the cell cycle	686:699	the cell cycle	686:699	Two phenotypes, switching from one to the other during the cell cycle, were detected.
29526322	10	47	theme	sub-cellular	1560:1571	arg1	localization					1573:1584	the NCX3 sub-cellular localization	1551:1584	the NCX3 sub-cellular localization	1551:1584	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	8	48	theme	mutant	1144:1149	arg1	Introduction					1094:1105	Introduction	1094:1105	Introduction of an N-glycosylation deficient NCX3 mutant	1094:1149	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	7	49	theme	N45	967:969	arg1	switch					1000:1005	an on-off switch	990:1005	an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER	990:1091	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	7	49	theme	N45	967:969	arg1	site					971:974	the N45 site	963:974	the N45 site	963:974	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	7	50	theme	N45	887:889	arg1	site					891:894	the N45 site	883:894	the N45 site	883:894	Glycosylation of NCX3 at the N45 site was required for targeting the protein to the plasma membrane, and the N45 site functioned as an on-off switch for the translocation of NCX3 to either the plasma membrane or the membrane of the ER.
29526322	8	51	theme	NCX3	1139:1142	arg1	mutant					1144:1149	an N-glycosylation deficient NCX3 mutant	1110:1149	an N-glycosylation deficient NCX3 mutant	1110:1149	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	9	52	from	cytosol	1362:1368	arg1	Ca2+					1347:1350	Ca2+	1347:1350	Ca2+	1347:1350	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	9	52	from	cytosol	1362:1368	arg1	ions					1341:1344	calcium ions	1333:1344	calcium ions (Ca2+) from the cytosol to the ER	1333:1378	This was accompanied by accumulation of de-glycosylated NCX3 in the cytosol (that is in the ER), where it transported calcium ions (Ca2+) from the cytosol to the ER.
29526322	6	53	theme	ER	815:816	arg1	membrane					818:825	the ER membrane	811:825	the ER membrane	811:825	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	10	54	theme	SH-SY5Y	1467:1473	arg1	cells					1475:1479	SH-SY5Y cells	1467:1479	SH-SY5Y cells	1467:1479	These results, obtained in transfected HEK293T and HeLa and confirmed endogenously in SH-SY5Y cells, suggest that cells can use a dynamic Ca2+ signaling toolkit in which the NCX3 sub-cellular localization changes in synchrony with the cell cycle.
29526322	4	55	theme	subtype	580:586	arg1	localization					556:567	the subcellular localization	540:567	the subcellular localization of the NCX subtype 3 (NCX3)	540:595	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	4	55	theme	subtype	580:586	arg1	impact					605:610	its impact	601:610	its impact on the cell cycle	601:628	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	6	56	theme	plasma	747:752	arg1	membrane					754:761	the plasma membrane	743:761	the plasma membrane	743:761	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	1	57	theme	membrane	129:136	arg1	exchanger					108:116	The Na+/Ca2+ exchanger	95:116	The Na+/Ca2+ exchanger (NCX)	95:122	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	1	57	theme	membrane	129:136	arg1	antiporter					138:147	a membrane antiporter	127:147	a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER)	127:293	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29526322	4	58	theme	NCX	576:578	arg1	subtype					580:586	NCX subtype 3	576:588	the NCX subtype 3 (NCX3)	572:595	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	4	58	theme	NCX	576:578	arg1	NCX3					591:594	NCX3	591:594	NCX3	591:594	Here we investigated the subcellular localization of the NCX subtype 3 (NCX3) and its impact on the cell cycle.
29526322	6	59	from	NCX3	803:806	arg1	membrane					754:761	the plasma membrane	743:761	the plasma membrane	743:761	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	6	59	from	NCX3	803:806	arg1	membrane					818:825	the ER membrane	811:825	the ER membrane	811:825	One phenotype was NCX3 in the plasma membrane during S and M phase, and the other was NCX3 in the ER membrane during resting and interphase.
29526322	2	60	theme	NCX	357:359	arg1	proteins					361:368	unique NCX proteins	350:368	unique NCX proteins	350:368	In humans, three genes have been identified, encoding unique NCX proteins.
29526322	8	61	theme	N-glycosylation	1113:1127	arg1	mutant					1144:1149	an N-glycosylation deficient NCX3 mutant	1110:1149	an N-glycosylation deficient NCX3 mutant	1110:1149	Introduction of an N-glycosylation deficient NCX3 mutant led to an arrest of cells in the G0/G1 phase of the cell cycle.
29526322	3	62	theme	different	479:487	arg1	subtypes					489:496	different subtypes	479:496	different subtypes	479:496	Although extensively studied, the NCX's sub-cellular localization and mechanisms regulating the activity of different subtypes are still ambiguous.
29526322	0	63	theme	cell	83:86	arg1	cycle					88:92	cell cycle	83:92	cell cycle	83:92	Glycosylation controls sodium-calcium exchanger 3 sub-cellular localization during cell cycle.
29526322	3	64	theme	subtypes	489:496	arg1	activity					467:474	the activity	463:474	the activity of different subtypes	463:496	Although extensively studied, the NCX's sub-cellular localization and mechanisms regulating the activity of different subtypes are still ambiguous.
29526322	1	65	theme	nuclear	224:230	arg1	envelope					232:239	the nuclear envelope	220:239	the nuclear envelope	220:239	The Na+/Ca2+ exchanger (NCX) is a membrane antiporter that has been identified in the plasma membrane, the inner membrane of the nuclear envelope and in the membrane of the endoplasmic reticulum (ER).
29793953	2	0	theme	little	562:567	arg1	HBsAg					598:602	HBsAg	598:602	HBsAg	598:602	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	2	0	theme	little	562:567	arg1	antigen					589:595	very little hepatitis B surface antigen	557:595	very little hepatitis B surface antigen (HBsAg)	557:603	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	12	1	theme	HepG2	2278:2282	arg1	cells					2284:2288	HepG2 cells	2278:2288	HepG2 cells	2278:2288	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	14	2	theme	HepaRG	2678:2683	arg1	cells					2685:2689	HepaRG cells	2678:2689	HepaRG cells	2678:2689	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	10	3	theme	hepatitis	2077:2085	arg1	antigen					2097:2103	very little hepatitis B surface antigen	2065:2103	very little hepatitis B surface antigen	2065:2103	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	8	4	theme	HepG2	1590:1594	arg1	cells					1596:1600	HepG2 cells	1590:1600	HepG2 cells	1590:1600	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	6	5	gly	glycosylated	1173:1184	arg1	NTCP					1122:1125	Tagged NTCP	1115:1125	Tagged NTCP introduced to both HepG2 and HepaRG cells	1115:1167	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	13	6	theme	culture-derived	2554:2568	arg1	HBV					2570:2572	cell culture-derived HBV	2549:2572	cell culture-derived HBV	2549:2572	Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens.
29793953	8	7	theme	HepaRG	1656:1661	arg1	cells					1678:1682	HepaRG and HepG2/NTCP cells	1656:1682	HepaRG and HepG2/NTCP cells	1656:1682	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	12	8	dep	either	2357:2362	arg1	sites					2372:2376	sites	2372:2376	sites	2372:2376	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	7	9	gly	nonglycosylated	1387:1401	arg1	forms					1403:1407	both the singly glycosylated and nonglycosylated forms	1354:1407	forms	1403:1407	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	7	10	theme	cHBV	1436:1439	arg1	infection					1441:1449	cHBV infection	1436:1449	cHBV infection in HepG2 cells	1436:1464	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	9	11	theme	HepaRG	1870:1875	arg1	cells					1877:1881	differentiated HepaRG cells	1855:1881	differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor	1855:1959	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	1	12	theme	culture-derived	404:418	arg1	particles					431:439	cell culture-derived HBV (cHBV) particles	399:439	cell culture-derived HBV (cHBV) particles	399:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	8	13	theme	HepG2/NTCP	1667:1676	arg1	cells					1678:1682	HepaRG and HepG2/NTCP cells	1656:1682	HepaRG and HepG2/NTCP cells	1656:1682	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	7	14	gly	glycosylated	1370:1381	arg1	forms					1403:1407	both the singly glycosylated and nonglycosylated forms	1354:1407	forms	1403:1407	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	12	15	link	serum-derived	2465:2477	arg1	HBV					2479:2481	serum-derived HBV	2465:2481	serum-derived HBV	2465:2481	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	6	16	theme	N-linked	1218:1225	arg1	glycosylation					1227:1239	N-linked glycosylation	1218:1239	N-linked glycosylation	1218:1239	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	2	17	theme	B	579:579	arg1	HBsAg					598:602	HBsAg	598:602	HBsAg	598:602	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	2	17	theme	B	579:579	arg1	antigen					589:595	very little hepatitis B surface antigen	557:595	very little hepatitis B surface antigen (HBsAg)	557:603	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	14	18	theme	culture-derived	2854:2868	arg1	HBV					2870:2872	cell culture-derived HBV	2849:2872	cell culture-derived HBV	2849:2872	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	9	19	theme	HepG2	1892:1896	arg1	cells					1898:1902	HepG2 cells	1892:1902	differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor	1855:1959	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	1	20	from	overexpression	261:274	arg1	lines					290:294	HepG2 cell lines	279:294	HepG2 cell lines	279:294	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	2	21	theme	serum-derived	520:532	arg1	sHBV					539:542	sHBV	539:542	sHBV	539:542	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	2	21	theme	serum-derived	520:532	arg1	HBV					534:536	patient serum-derived HBV	512:536	patient serum-derived HBV (sHBV)	512:543	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	10	22	theme	culture-derived	2133:2147	arg1	HBV					2149:2151	cell culture-derived HBV	2128:2151	cell culture-derived HBV	2128:2151	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	9	23	theme	accepted	1939:1946	arg1	NTCP					1919:1922	NTCP	1919:1922	NTCP	1919:1922	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	9	23	theme	accepted	1939:1946	arg1	receptor					1952:1959	the currently accepted HBV receptor	1925:1959	the currently accepted HBV receptor	1925:1959	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	12	24	gly	glycosylation	2323:2335	arg2	two					2310:2312	two	2310:2312	two	2310:2312	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	12	24	gly	glycosylation	2323:2335	arg2	sites					2337:2341	two N-linked glycosylation sites	2310:2341	two N-linked glycosylation sites	2310:2341	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	12	25	gly	glycosylated	2294:2305	arg2	sites					2337:2341	two N-linked glycosylation sites	2310:2341	two N-linked glycosylation sites	2310:2341	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	12	25	gly	glycosylated	2294:2305	arg1	NTCP					2259:2262	NTCP	2259:2262	NTCP introduced to HepG2 cells	2259:2288	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	10	26	theme	little	2070:2075	arg1	antigen					2097:2103	very little hepatitis B surface antigen	2065:2103	very little hepatitis B surface antigen	2065:2103	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	7	27	theme	subcellular	1323:1333	arg1	localization					1335:1346	its subcellular localization	1319:1346	its subcellular localization	1319:1346	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	6	28	link	N-linked	1218:1225	arg1	glycosylation					1227:1239	N-linked glycosylation	1218:1239	N-linked glycosylation	1218:1239	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	8	29	theme	different	1718:1726	arg1	ratios					1740:1745	different HBsAg/HBeAg ratios	1718:1745	different HBsAg/HBeAg ratios	1718:1745	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	1	30	theme	hepatitis	219:227	arg1	HBV					238:240	HBV	238:240	HBV	238:240	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	30	theme	hepatitis	219:227	arg1	virus					231:235	a hepatitis B virus	217:235	a hepatitis B virus (HBV) receptor	217:250	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	7	31	from	infection	1441:1449	arg1	cells					1460:1464	HepG2 cells	1454:1464	HepG2 cells	1454:1464	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	4	32	theme	NTCP	839:842	arg1	protein					844:850	Endogenous NTCP protein	828:850	Endogenous NTCP protein from differentiated HepaRG cells	828:883	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	14	33	theme	antigen	2807:2813	arg1	production					2815:2824	balanced viral antigen production	2792:2824	balanced viral antigen production	2792:2824	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	6	34	gly	glycosylation	1227:1239	arg2	sites					1209:1213	sites	1209:1213	sites of N-linked glycosylation	1209:1239	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	6	34	gly	glycosylation	1227:1239	arg2	glycosylation					1227:1239	N-linked glycosylation	1218:1239	N-linked glycosylation	1218:1239	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	12	35	theme	N-linked	2314:2321	arg1	sites					2337:2341	two N-linked glycosylation sites	2310:2341	two N-linked glycosylation sites	2310:2341	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	14	36	theme	balanced	2792:2799	arg1	production					2815:2824	balanced viral antigen production	2792:2824	balanced viral antigen production	2792:2824	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	2	37	theme	differentiated	638:651	arg1	cells					660:664	differentiated HepaRG cells	638:664	differentiated HepaRG cells	638:664	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	9	38	theme	HBV	1948:1950	arg1	NTCP					1919:1922	NTCP	1919:1922	NTCP	1919:1922	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	9	38	theme	HBV	1948:1950	arg1	receptor					1952:1959	the currently accepted HBV receptor	1925:1959	the currently accepted HBV receptor	1925:1959	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	1	39	theme	large	385:389	arg1	dose					391:394	a large dose	383:394	a large dose of cell culture-derived HBV (cHBV) particles	383:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	8	40	theme	cHBV	1757:1760	arg1	infection					1762:1770	cHBV infection	1757:1770	cHBV infection	1757:1770	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	1	41	theme	Sodium	140:145	arg1	receptor					243:250	a hepatitis B virus (HBV) receptor	217:250	a hepatitis B virus (HBV) receptor	217:250	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	41	theme	Sodium	140:145	arg1	NTCP					188:191	NTCP	188:191	NTCP	188:191	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	41	theme	Sodium	140:145	arg1	polypeptide					175:185	Sodium taurocholate cotransporting polypeptide	140:185	Sodium taurocholate cotransporting polypeptide (NTCP)	140:192	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	3	42	theme	different	785:793	arg1	behaviors					795:803	the different behaviors	781:803	the different behaviors of the two cell types	781:825	Here, we investigated whether NTCP could explain the different behaviors of the two cell types.
29793953	2	43	theme	NTCP-reconstituted	451:468	arg1	cells					476:480	NTCP-reconstituted HepG2 cells	451:480	NTCP-reconstituted HepG2 cells	451:480	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	4	44	theme	HepaRG	872:877	arg1	cells					879:883	differentiated HepaRG cells	857:883	differentiated HepaRG cells	857:883	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	7	45	theme	surface	1287:1293	arg1	availability					1295:1306	cell surface availability	1282:1306	cell surface availability of NTCP or its subcellular localization	1282:1346	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	0	46	theme	Cotransporting	64:77	arg1	Polypeptide					79:89	Sodium Taurocholate Cotransporting Polypeptide	44:89	Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro	44:137	N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.
29793953	5	47	theme	null	1102:1105	arg1	mutant					1107:1112	the null mutant	1098:1112	the null mutant	1098:1112	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant.
29793953	1	48	theme	cotransporting	160:173	arg1	receptor					243:250	a hepatitis B virus (HBV) receptor	217:250	a hepatitis B virus (HBV) receptor	217:250	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	48	theme	cotransporting	160:173	arg1	NTCP					188:191	NTCP	188:191	NTCP	188:191	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	48	theme	cotransporting	160:173	arg1	polypeptide					175:185	Sodium taurocholate cotransporting polypeptide	140:185	Sodium taurocholate cotransporting polypeptide (NTCP)	140:192	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	3	49	theme	types	821:825	arg1	behaviors					795:803	the different behaviors	781:803	the different behaviors of the two cell types	781:825	Here, we investigated whether NTCP could explain the different behaviors of the two cell types.
29793953	12	50	theme	serum-derived	2465:2477	arg1	HBV					2479:2481	serum-derived HBV	2465:2481	serum-derived HBV	2465:2481	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	10	51	theme	serum-derived	2025:2037	arg1	particles					2043:2051	patient serum-derived HBV particles	2017:2051	patient serum-derived HBV particles	2017:2051	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	0	52	theme	Hepatitis	102:110	arg1	Virus					114:118	Hepatitis B Virus	102:118	Hepatitis B Virus Infection	102:128	N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.
29793953	1	53	theme	B	338:338	arg1	HBeAg					351:355	HBeAg	351:355	HBeAg	351:355	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	53	theme	B	338:338	arg1	antigen					342:348	hepatitis B e antigen	328:348	hepatitis B e antigen (HBeAg)	328:356	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	6	54	theme	HepaRG	1156:1161	arg1	cells					1163:1167	HepaRG cells	1156:1167	HepaRG cells	1156:1167	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	4	55	theme	coding	922:927	arg1	sequence					929:936	wild-type coding sequence	912:936	wild-type coding sequence	912:936	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	0	56	theme	Virus	114:118	arg1	Infection					120:128	Hepatitis B Virus Infection	102:128	Hepatitis B Virus Infection	102:128	N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.
29793953	1	57	theme	antigen	342:348	arg1	secretion					315:323	efficient secretion	305:323	efficient secretion of hepatitis B e antigen (HBeAg)	305:356	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	13	58	theme	cell	2549:2552	arg1	HBV					2570:2572	cell culture-derived HBV	2549:2572	cell culture-derived HBV	2549:2572	Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens.
29793953	7	59	theme	cell	1282:1285	arg1	availability					1295:1306	cell surface availability	1282:1306	cell surface availability of NTCP or its subcellular localization	1282:1346	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	8	60	theme	nonglycosylated	1482:1496	arg1	NTCP					1498:1501	nonglycosylated NTCP	1482:1501	nonglycosylated NTCP	1482:1501	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	0	61	theme	N-Linked	0:7	arg1	Glycosylation					9:21	N-Linked Glycosylation	0:21	N-Linked Glycosylation	0:21	N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.
29793953	9	62	theme	host	1789:1792	arg1	s					1801:1801	The responsible host factor(s)	1773:1802	The responsible host factor(s)	1773:1802	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	2	63	theme	cHBV	615:618	arg1	infection					620:628	cHBV infection	615:628	cHBV infection	615:628	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	7	64	dep	forms	1403:1407	arg1	both					1354:1357	both	1354:1357	both	1354:1357	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	1	65	theme	cell	285:288	arg1	lines					290:294	HepG2 cell lines	279:294	HepG2 cell lines	279:294	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	5	66	theme	NTCP	994:997	arg1	construct					1010:1018	an epitope-tagged NTCP expression construct	976:1018	an epitope-tagged NTCP expression construct	976:1018	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant.
29793953	11	67	gly	nonglycosylated	2201:2215	arg1	NTCP					2217:2220	nonglycosylated NTCP	2201:2220	nonglycosylated NTCP	2201:2220	We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence.
29793953	13	68	link	culture-derived	2554:2568	arg1	HBV					2570:2572	cell culture-derived HBV	2549:2572	cell culture-derived HBV	2549:2572	Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens.
29793953	11	69	theme	HepaRG	2178:2183	arg1	cells					2185:2189	differentiated HepaRG cells	2163:2189	differentiated HepaRG cells	2163:2189	We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence.
29793953	8	70	theme	HepaRG	1534:1539	arg1	cells					1541:1545	differentiated HepaRG cells	1519:1545	differentiated HepaRG cells	1519:1545	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	14	71	link	culture-derived	2854:2868	arg1	HBV					2870:2872	cell culture-derived HBV	2849:2872	cell culture-derived HBV	2849:2872	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	0	72	theme	Sodium	44:49	arg1	Polypeptide					79:89	Sodium Taurocholate Cotransporting Polypeptide	44:89	Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro	44:137	N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.
29793953	12	73	dep	glycosylated	2294:2305	arg1	failed					2378:2383	failed	2378:2383	failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV	2378:2481	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	1	74	theme	efficient	305:313	arg1	secretion					315:323	efficient secretion	305:323	efficient secretion of hepatitis B e antigen (HBeAg)	305:356	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	14	75	theme	efficient	2708:2716	arg1	infection					2718:2726	efficient infection	2708:2726	efficient infection by serum-derived HBV	2708:2747	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	1	76	theme	B	229:229	arg1	HBV					238:240	HBV	238:240	HBV	238:240	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	76	theme	B	229:229	arg1	virus					231:235	a hepatitis B virus	217:235	a hepatitis B virus (HBV) receptor	217:250	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	7	77	theme	HepG2	1454:1458	arg1	cells					1460:1464	HepG2 cells	1454:1464	HepG2 cells	1454:1464	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	9	78	theme	identified.IMPORTANCE	1818:1838	arg1	HBV					1840:1842	identified.IMPORTANCE HBV	1818:1842	identified.IMPORTANCE HBV	1818:1842	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	10	79	theme	B	2087:2087	arg1	antigen					2097:2103	very little hepatitis B surface antigen	2065:2103	very little hepatitis B surface antigen	2065:2103	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	8	80	theme	cHBV	1572:1575	arg1	infection					1577:1585	cHBV infection	1572:1585	cHBV infection in HepG2 cells	1572:1600	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	9	81	dep	host	1789:1792	arg1	responsible					1777:1787	responsible	1777:1787	responsible	1777:1787	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	8	82	theme	differential	1625:1636	arg1	susceptibility					1638:1651	differential susceptibility	1625:1651	differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios	1625:1745	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	1	83	link	culture-derived	404:418	arg1	particles					431:439	cell culture-derived HBV (cHBV) particles	399:439	cell culture-derived HBV (cHBV) particles	399:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	12	84	link	N-linked	2314:2321	arg1	sites					2337:2341	two N-linked glycosylation sites	2310:2341	two N-linked glycosylation sites	2310:2341	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	9	85	theme	differentiated	1855:1868	arg1	cells					1877:1881	differentiated HepaRG cells	1855:1881	differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor	1855:1959	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	1	86	theme	cell	399:402	arg1	particles					431:439	cell culture-derived HBV (cHBV) particles	399:439	cell culture-derived HBV (cHBV) particles	399:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	7	87	theme	capable	1415:1421	arg1	forms					1403:1407	both the singly glycosylated and nonglycosylated forms	1354:1407	forms	1403:1407	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	7	88	theme	nonglycosylated	1387:1401	arg1	forms					1403:1407	both the singly glycosylated and nonglycosylated forms	1354:1407	forms	1403:1407	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	10	89	theme	surface	2089:2095	arg1	antigen					2097:2103	very little hepatitis B surface antigen	2065:2103	very little hepatitis B surface antigen	2065:2103	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	6	90	theme	glycosylation	1227:1239	arg1	sites					1209:1213	sites	1209:1213	sites of N-linked glycosylation	1209:1239	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	6	90	theme	glycosylation	1227:1239	arg1	glycosylation					1227:1239	N-linked glycosylation	1218:1239	N-linked glycosylation	1218:1239	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	1	91	theme	HBV	420:422	arg1	particles					431:439	cell culture-derived HBV (cHBV) particles	399:439	cell culture-derived HBV (cHBV) particles	399:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	2	92	theme	surface	581:587	arg1	HBsAg					598:602	HBsAg	598:602	HBsAg	598:602	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	2	92	theme	surface	581:587	arg1	antigen					589:595	very little hepatitis B surface antigen	557:595	very little hepatitis B surface antigen (HBsAg)	557:603	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	7	93	theme	glycosylated	1370:1381	arg1	forms					1403:1407	both the singly glycosylated and nonglycosylated forms	1354:1407	forms	1403:1407	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	2	94	link	serum-derived	520:532	arg1	sHBV					539:542	sHBV	539:542	sHBV	539:542	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	2	94	link	serum-derived	520:532	arg1	HBV					534:536	patient serum-derived HBV	512:536	patient serum-derived HBV (sHBV)	512:543	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	1	95	theme	cHBV	425:428	arg1	particles					431:439	cell culture-derived HBV (cHBV) particles	399:439	cell culture-derived HBV (cHBV) particles	399:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	8	96	theme	cells	1678:1682	arg1	susceptibility					1638:1651	differential susceptibility	1625:1651	differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios	1625:1745	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	14	97	theme	unique	2668:2673	arg1	factors					2660:2666	host factors	2655:2666	host factors unique to HepaRG cells	2655:2689	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	2	98	theme	hepatitis	569:577	arg1	HBsAg					598:602	HBsAg	598:602	HBsAg	598:602	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	2	98	theme	hepatitis	569:577	arg1	antigen					589:595	very little hepatitis B surface antigen	557:595	very little hepatitis B surface antigen (HBsAg)	557:603	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	14	99	theme	cell	2849:2852	arg1	HBV					2870:2872	cell culture-derived HBV	2849:2872	cell culture-derived HBV	2849:2872	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	8	100	from	infection	1577:1585	arg1	cells					1596:1600	HepG2 cells	1590:1600	HepG2 cells	1590:1600	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	1	101	theme	particles	431:439	arg1	dose					391:394	a large dose	383:394	a large dose of cell culture-derived HBV (cHBV) particles	383:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	8	102	theme	cHBV	1687:1690	arg1	infection					1704:1712	cHBV versus sHBV infection	1687:1712	cHBV versus sHBV infection	1687:1712	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	14	103	theme	host	2655:2658	arg1	factors					2660:2666	host factors	2655:2666	host factors unique to HepaRG cells	2655:2689	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	4	104	theme	differentiated	857:870	arg1	cells					879:883	differentiated HepaRG cells	857:883	differentiated HepaRG cells	857:883	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	10	105	theme	cell	2128:2131	arg1	HBV					2149:2151	cell culture-derived HBV	2128:2151	cell culture-derived HBV	2128:2151	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	5	106	theme	cHBV	1050:1053	arg1	susceptibility					1055:1068	cHBV susceptibility	1050:1068	higher sHBV but not cHBV susceptibility	1030:1068	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant.
29793953	8	107	theme	sHBV	1699:1702	arg1	infection					1704:1712	cHBV versus sHBV infection	1687:1712	cHBV versus sHBV infection	1687:1712	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	7	108	theme	localization	1335:1346	arg1	availability					1295:1306	cell surface availability	1282:1306	cell surface availability of NTCP or its subcellular localization	1282:1346	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	12	109	theme	culture-derived	2414:2428	arg1	HBV					2430:2432	cell culture-derived HBV	2409:2432	cell culture-derived HBV	2409:2432	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	4	110	theme	Endogenous	828:837	arg1	protein					844:850	Endogenous NTCP protein	828:850	Endogenous NTCP protein from differentiated HepaRG cells	828:883	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	12	111	theme	glycosylation	2323:2335	arg1	sites					2337:2341	two N-linked glycosylation sites	2310:2341	two N-linked glycosylation sites	2310:2341	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	14	112	theme	viral	2801:2805	arg1	production					2815:2824	balanced viral antigen production	2792:2824	balanced viral antigen production	2792:2824	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	2	113	theme	HepaRG	653:658	arg1	cells					660:664	differentiated HepaRG cells	638:664	differentiated HepaRG cells	638:664	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	5	114	theme	higher	1030:1035	arg1	sHBV					1037:1040	higher sHBV	1030:1040	higher sHBV but not cHBV susceptibility	1030:1068	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant.
29793953	8	115	theme	HBsAg/HBeAg	1728:1738	arg1	ratios					1740:1745	different HBsAg/HBeAg ratios	1718:1745	different HBsAg/HBeAg ratios	1718:1745	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	10	116	link	culture-derived	2133:2147	arg1	HBV					2149:2151	cell culture-derived HBV	2128:2151	cell culture-derived HBV	2128:2151	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	7	117	theme	NTCP	1311:1314	arg1	availability					1295:1306	cell surface availability	1282:1306	cell surface availability of NTCP or its subcellular localization	1282:1346	Mutating N5, N11, or both did not alter cell surface availability of NTCP or its subcellular localization, with both the singly glycosylated and nonglycosylated forms still capable of mediating cHBV infection in HepG2 cells.
29793953	10	118	link	serum-derived	2025:2037	arg1	particles					2043:2051	patient serum-derived HBV particles	2017:2051	patient serum-derived HBV particles	2017:2051	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	1	119	theme	taurocholate	147:158	arg1	receptor					243:250	a hepatitis B virus (HBV) receptor	217:250	a hepatitis B virus (HBV) receptor	217:250	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	119	theme	taurocholate	147:158	arg1	NTCP					188:191	NTCP	188:191	NTCP	188:191	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	119	theme	taurocholate	147:158	arg1	polypeptide					175:185	Sodium taurocholate cotransporting polypeptide	140:185	Sodium taurocholate cotransporting polypeptide (NTCP)	140:192	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	11	120	theme	wild-type	2232:2240	arg1	sequence					2249:2256	a wild-type coding sequence	2230:2256	a wild-type coding sequence	2230:2256	We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence.
29793953	12	121	link	culture-derived	2414:2428	arg1	HBV					2430:2432	cell culture-derived HBV	2409:2432	cell culture-derived HBV	2409:2432	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29793953	10	122	theme	HepG2/NTCP	1971:1980	arg1	cells					1982:1986	HepG2/NTCP cells	1971:1986	HepG2/NTCP cells	1971:1986	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	8	123	gly	nonglycosylated	1482:1496	arg1	NTCP					1498:1501	nonglycosylated NTCP	1482:1501	nonglycosylated NTCP	1482:1501	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	2	124	theme	patient	512:518	arg1	sHBV					539:542	sHBV	539:542	sHBV	539:542	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	2	124	theme	patient	512:518	arg1	HBV					534:536	patient serum-derived HBV	512:536	patient serum-derived HBV (sHBV)	512:543	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	10	125	theme	patient	2017:2023	arg1	particles					2043:2051	patient serum-derived HBV particles	2017:2051	patient serum-derived HBV particles	2017:2051	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	0	126	theme	B	112:112	arg1	Virus					114:118	Hepatitis B Virus	102:118	Hepatitis B Virus Infection	102:128	N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.
29793953	1	127	theme	hepatitis	328:336	arg1	HBeAg					351:355	HBeAg	351:355	HBeAg	351:355	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	127	theme	hepatitis	328:336	arg1	antigen					342:348	hepatitis B e antigen	328:348	hepatitis B e antigen (HBeAg)	328:356	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	3	128	theme	cell	816:819	arg1	types					821:825	the two cell types	808:825	the two cell types	808:825	Here, we investigated whether NTCP could explain the different behaviors of the two cell types.
29793953	1	129	theme	e	340:340	arg1	HBeAg					351:355	HBeAg	351:355	HBeAg	351:355	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	129	theme	e	340:340	arg1	antigen					342:348	hepatitis B e antigen	328:348	hepatitis B e antigen (HBeAg)	328:356	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	5	130	theme	HepaRG	939:944	arg1	cells					946:950	HepaRG cells	939:950	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct	939:1018	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant.
29793953	2	131	theme	HepG2	470:474	arg1	cells					476:480	NTCP-reconstituted HepG2 cells	451:480	NTCP-reconstituted HepG2 cells	451:480	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	13	132	theme	HepRG	2507:2511	arg1	cells					2513:2517	HepRG cells	2507:2517	HepRG cells	2507:2517	Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens.
29793953	11	133	theme	coding	2242:2247	arg1	sequence					2249:2256	a wild-type coding sequence	2230:2256	a wild-type coding sequence	2230:2256	We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence.
29793953	4	134	gly	unglycosylated	889:902	arg1	protein					844:850	Endogenous NTCP protein	828:850	Endogenous NTCP protein from differentiated HepaRG cells	828:883	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	11	135	theme	differentiated	2163:2176	arg1	cells					2185:2189	differentiated HepaRG cells	2163:2189	differentiated HepaRG cells	2163:2189	We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence.
29793953	4	136	from	cells	879:883	arg1	protein					844:850	Endogenous NTCP protein	828:850	Endogenous NTCP protein from differentiated HepaRG cells	828:883	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	13	137	theme	viral	2611:2615	arg1	antigens					2617:2624	the two viral antigens	2603:2624	the two viral antigens	2603:2624	Overexpressing NTCP in HepRG cells did not increase infection by cell culture-derived HBV or distort the ratio between the two viral antigens.
29793953	1	138	with	challenge	368:376	arg1	dose					391:394	a large dose	383:394	a large dose of cell culture-derived HBV (cHBV) particles	383:439	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	9	139	theme	factor	1794:1799	arg1	s					1801:1801	The responsible host factor(s)	1773:1802	The responsible host factor(s)	1773:1802	The responsible host factor(s) remains to be identified.IMPORTANCE HBV can infect differentiated HepaRG cells and also HepG2 cells overexpressing NTCP, the currently accepted HBV receptor.
29793953	8	140	theme	differentiated	1519:1532	arg1	cells					1541:1545	differentiated HepaRG cells	1519:1545	differentiated HepaRG cells	1519:1545	In conclusion, nonglycosylated NTCP is expressed by differentiated HepaRG cells and capable of mediating cHBV infection in HepG2 cells, but it cannot explain differential susceptibility of HepaRG and HepG2/NTCP cells to cHBV versus sHBV infection and different HBsAg/HBeAg ratios following cHBV infection.
29793953	2	141	theme	sHBV	716:719	arg1	particles					721:729	sHBV particles	716:729	sHBV particles	716:729	However, NTCP-reconstituted HepG2 cells are inefficiently infected by patient serum-derived HBV (sHBV) and release very little hepatitis B surface antigen (HBsAg) following cHBV infection, unlike differentiated HepaRG cells, which are naturally susceptible to both cHBV and sHBV particles.
29793953	1	142	theme	HepG2	279:283	arg1	lines					290:294	HepG2 cell lines	279:294	HepG2 cell lines	279:294	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	5	143	theme	epitope-tagged	979:992	arg1	construct					1010:1018	an epitope-tagged NTCP expression construct	976:1018	an epitope-tagged NTCP expression construct	976:1018	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant.
29793953	14	144	theme	serum-derived	2731:2743	arg1	HBV					2745:2747	serum-derived HBV	2731:2747	serum-derived HBV	2731:2747	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	11	145	theme	nonglycosylated	2201:2215	arg1	NTCP					2217:2220	nonglycosylated NTCP	2201:2220	nonglycosylated NTCP	2201:2220	We found differentiated HepaRG cells expressed nonglycosylated NTCP despite a wild-type coding sequence.
29793953	4	146	theme	wild-type	912:920	arg1	sequence					929:936	wild-type coding sequence	912:936	wild-type coding sequence	912:936	Endogenous NTCP protein from differentiated HepaRG cells was unglycosylated despite wild-type coding sequence.
29793953	0	147	theme	Taurocholate	51:62	arg1	Polypeptide					79:89	Sodium Taurocholate Cotransporting Polypeptide	44:89	Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro	44:137	N-Linked Glycosylation Is Not Essential for Sodium Taurocholate Cotransporting Polypeptide To Mediate Hepatitis B Virus Infection In Vitro.
29793953	5	148	theme	expression	999:1008	arg1	construct					1010:1018	an epitope-tagged NTCP expression construct	976:1018	an epitope-tagged NTCP expression construct	976:1018	HepaRG cells stably transfected with an epitope-tagged NTCP expression construct displayed higher sHBV but not cHBV susceptibility than cells transfected with the null mutant.
29793953	6	149	theme	Tagged	1115:1120	arg1	NTCP					1122:1125	Tagged NTCP	1115:1125	Tagged NTCP introduced to both HepG2 and HepaRG cells	1115:1167	Tagged NTCP introduced to both HepG2 and HepaRG cells was glycosylated, with N5 and N11 being sites of N-linked glycosylation.
29793953	14	150	link	serum-derived	2731:2743	arg1	HBV					2745:2747	serum-derived HBV	2731:2747	serum-derived HBV	2731:2747	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	14	151	theme	other	2762:2766	arg1	factors					2754:2760	factors	2754:2760	factors other than NTCP	2754:2776	These findings suggest that host factors unique to HepaRG cells are required for efficient infection by serum-derived HBV, and factors other than NTCP contribute to balanced viral antigen production following infection by cell culture-derived HBV.
29793953	1	152	theme	virus	231:235	arg1	receptor					243:250	a hepatitis B virus (HBV) receptor	217:250	a hepatitis B virus (HBV) receptor	217:250	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	1	152	theme	virus	231:235	arg1	polypeptide					175:185	Sodium taurocholate cotransporting polypeptide	140:185	Sodium taurocholate cotransporting polypeptide (NTCP)	140:192	Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a hepatitis B virus (HBV) receptor, and its overexpression in HepG2 cell lines leads to efficient secretion of hepatitis B e antigen (HBeAg) following challenge with a large dose of cell culture-derived HBV (cHBV) particles.
29793953	10	153	theme	HBV	2039:2041	arg1	particles					2043:2051	patient serum-derived HBV particles	2017:2051	patient serum-derived HBV particles	2017:2051	However, HepG2/NTCP cells remain poorly susceptible to patient serum-derived HBV particles and release very little hepatitis B surface antigen following infection by cell culture-derived HBV.
29793953	12	154	theme	cell	2409:2412	arg1	HBV					2430:2432	cell culture-derived HBV	2409:2432	cell culture-derived HBV	2409:2432	NTCP introduced to HepG2 cells was glycosylated at two N-linked glycosylation sites, but mutating either or both sites failed to prevent infection by cell culture-derived HBV or to confer susceptibility to serum-derived HBV.
29541627	1	0	link	O-linked	258:265	arg1	glycosylations					267:280	N- and O-linked glycosylations	251:280	N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins	251:368	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	5	1	theme	genetic	1208:1214	arg1	variants					1216:1223	genetic variants	1208:1223	genetic variants	1208:1223	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	2	from	alteration	1148:1157	arg1	environment					1193:1203	polarity environment	1184:1203	polarity environment	1184:1203	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	2	from	alteration	1148:1157	arg1	charge					1173:1178	side-chain charge	1162:1178	side-chain charge	1162:1178	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	2	from	alteration	1148:1157	arg1	vicinity					1246:1253	the vicinity	1242:1253	the vicinity of Asn-containing epitope	1242:1279	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	3	3	dep	acids	736:740	arg1	designated					743:752	designated	743:752	designated as L, O, A, P, and N groups	743:780	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	1	4	theme	structural	178:187	arg1	diversity					204:212	The structural and functional diversity	174:212	The structural and functional diversity of the human proteome	174:234	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	1	5	theme	functional	193:202	arg1	diversity					204:212	The structural and functional diversity	174:212	The structural and functional diversity of the human proteome	174:234	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	2	6	theme	acids	566:570	arg1	contribution					515:526	the contribution	511:526	the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation	511:626	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	0	7	theme	Constitutive	114:125	arg1	Proliferation					127:139	Proliferation	127:139	Proliferation	127:139	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	4	8	theme	polarity	937:944	arg1	combinations					946:957	particular charge and polarity combinations	915:957	combinations	946:957	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	6	9	theme	non-preferred	1775:1787	arg1	sites					1789:1793	preferred and non-preferred sites	1761:1793	preferred and non-preferred sites	1761:1793	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	6	10	from	sites	1789:1793	arg1	N-glycosylation					1742:1756	N-glycosylation	1742:1756	N-glycosylation at preferred and non-preferred sites	1742:1793	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	1	11	theme	human	221:225	arg1	proteome					227:234	the human proteome	217:234	the human proteome	217:234	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	6	12	theme	preferred	1761:1769	arg1	sites					1789:1793	preferred and non-preferred sites	1761:1793	preferred and non-preferred sites	1761:1793	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	3	13	theme	N	773:773	arg1	groups					775:780	N groups	773:780	N groups	773:780	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	0	14	theme	Cells	167:171	arg1	Adhesion					145:152	Adhesion	145:152	Adhesion	145:152	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	0	14	theme	Cells	167:171	arg1	Proliferation					127:139	Proliferation	127:139	Proliferation	127:139	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	4	15	theme	acidic	983:988	arg1	chain					1022:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain	962:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	1	16	theme	O-linked	258:265	arg1	glycosylations					267:280	N- and O-linked glycosylations	251:280	N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins	251:368	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	1	17	theme	membrane-associated	341:359	arg1	proteins					361:368	extracellular and membrane-associated proteins	323:368	extracellular and membrane-associated proteins	323:368	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	4	18	theme	environment	1028:1038	arg1	charge					926:931	particular charge and polarity combinations	915:957	charge	926:931	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	4	18	theme	environment	1028:1038	arg1	combinations					946:957	particular charge and polarity combinations	915:957	combinations	946:957	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	6	19	theme	mechanistic	1622:1632	arg1	constraints					1634:1644	polarity-based mechanistic constraints	1607:1644	polarity-based mechanistic constraints in N-glycosylation	1607:1663	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	4	20	theme	basic	991:995	arg1	chain					1022:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain	962:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	5	21	theme	Asn-containing	1258:1271	arg1	epitope					1273:1279	Asn-containing epitope	1258:1279	Asn-containing epitope	1258:1279	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	6	22	from	constraints	1634:1644	arg1	N-glycosylation					1649:1663	N-glycosylation	1649:1663	N-glycosylation	1649:1663	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	3	23	theme	literature-reported	861:879	arg1	proteins					887:894	130 literature-reported human proteins	857:894	130 literature-reported human proteins	857:894	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	2	24	theme	vicinal	552:558	arg1	acids					566:570	both penultimate and vicinal amino acids	531:570	both penultimate and vicinal amino acids	531:570	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	2	25	theme	penultimate	536:546	arg1	acids					566:570	both penultimate and vicinal amino acids	531:570	both penultimate and vicinal amino acids	531:570	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	6	26	theme	neoplastic	1697:1706	arg1	phenotype					1708:1716	the neoplastic phenotype	1693:1716	the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites	1693:1793	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	6	27	from	charge-	1595:1601	arg1	N-glycosylation					1649:1663	N-glycosylation	1649:1663	N-glycosylation	1649:1663	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	4	28	theme	chain	1022:1026	arg1	environment					1028:1038	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment	962:1038	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	2	29	theme	different	398:406	arg1	tools					422:426	different computational tools	398:426	different computational tools	398:426	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	0	30	theme	Charge	0:5	arg1	Preferences					20:30	Charge and Polarity Preferences	0:30	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.	0:172	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	5	31	from	sites	1381:1385	arg1	glycosylation					1336:1348	aberrant glycosylation	1327:1348	aberrant glycosylation	1327:1348	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	2	32	theme	genome-wide	455:465	arg1	mapping					467:473	in silico based genome-wide mapping	439:473	in silico based genome-wide mapping of 1,117 human proteins	439:497	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	0	33	theme	Polarity	11:18	arg1	Preferences					20:30	Charge and Polarity Preferences	0:30	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.	0:172	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	5	34	theme	polarity	1184:1191	arg1	environment					1193:1203	polarity environment	1184:1203	polarity environment	1184:1203	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	3	35	theme	environment	704:714	arg1	involvement					669:679	the non-canonical involvement	651:679	the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process	651:812	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	5	36	theme	aberrant	1327:1334	arg1	glycosylation					1336:1348	aberrant glycosylation	1327:1348	aberrant glycosylation	1327:1348	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	4	37	theme	polar	1011:1015	arg1	chain					1022:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain	962:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	0	38	theme	Genome-Wide	55:65	arg1	Study					77:81	A Genome-Wide In Silico Study	53:81	A Genome-Wide In Silico Study	53:81	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	5	39	theme	proteins	1400:1407	arg1	glycosylation					1306:1318	constitutive glycosylation	1293:1318	constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition	1293:1494	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	1	40	theme	extracellular	323:335	arg1	proteins					361:368	extracellular and membrane-associated proteins	323:368	extracellular and membrane-associated proteins	323:368	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	5	41	dep	glycosylation	1336:1348	arg1	e.g.					1321:1324	e.g.	1321:1324	e.g.	1321:1324	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	3	42	theme	charge	684:689	arg1	involvement					669:679	the non-canonical involvement	651:679	the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process	651:812	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	4	43	theme	acids	1078:1082	arg1	environment					1028:1038	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment	962:1038	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	3	44	theme	non-canonical	655:667	arg1	involvement					669:679	the non-canonical involvement	651:679	the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process	651:812	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	3	45	theme	acids	736:740	arg1	charge					684:689	charge	684:689	charge	684:689	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	3	45	theme	acids	736:740	arg1	environment					704:714	polarity environment	695:714	polarity environment	695:714	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	5	46	theme	constitutive	1417:1428	arg1	proliferation					1430:1442	constitutive proliferation	1417:1442	constitutive proliferation	1417:1442	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	1	47	theme	proteome	227:234	arg1	diversity					204:212	The structural and functional diversity	174:212	The structural and functional diversity of the human proteome	174:234	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	3	48	theme	classified	719:728	arg1	acids					736:740	classified amino acids	719:740	classified amino acids (designated as L, O, A, P, and N groups)	719:781	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	6	49	theme	proteins	1538:1545	arg1	mapping					1521:1527	The current genome-wide mapping	1497:1527	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues)	1497:1573	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	2	50	theme	human	484:488	arg1	proteins					490:497	1,117 human proteins	478:497	1,117 human proteins	478:497	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	4	51	theme	penultimate	1048:1058	arg1	acids					1078:1082	both penultimate and vicinal amino acids	1043:1082	both penultimate and vicinal amino acids	1043:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	5	52	gly	glycosylation	1336:1348	arg1	sites					1381:1385	preferred and non-preferred sites	1353:1385	preferred and non-preferred sites	1353:1385	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	52	gly	glycosylation	1336:1348	arg2	sites					1381:1385	preferred and non-preferred sites	1353:1385	preferred and non-preferred sites	1353:1385	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	1	53	theme	N-	251:252	arg1	glycosylations					267:280	N- and O-linked glycosylations	251:280	N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins	251:368	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	4	54	theme	vicinal	1064:1070	arg1	acids					1078:1082	both penultimate and vicinal amino acids	1043:1082	both penultimate and vicinal amino acids	1043:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	6	55	theme	genome-wide	1509:1519	arg1	mapping					1521:1527	The current genome-wide mapping	1497:1527	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues)	1497:1573	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	5	56	theme	variants	1216:1223	arg1	charge					1173:1178	side-chain charge	1162:1178	side-chain charge	1162:1178	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	56	theme	variants	1216:1223	arg1	environment					1193:1203	polarity environment	1184:1203	polarity environment	1184:1203	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	6	57	gly	N-glycosylation	1742:1756	arg2	sites					1789:1793	preferred and non-preferred sites	1761:1793	preferred and non-preferred sites	1761:1793	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	6	57	gly	N-glycosylation	1742:1756	arg1	sites					1789:1793	preferred and non-preferred sites	1761:1793	preferred and non-preferred sites	1761:1793	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	6	58	used	used	1579:1582	arg2	mapping					1521:1527	The current genome-wide mapping	1497:1527	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues)	1497:1573	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	5	59	theme	epithelial-to-mesenchymal	1459:1483	arg1	transition					1485:1494	epithelial-to-mesenchymal transition	1459:1494	epithelial-to-mesenchymal transition	1459:1494	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	4	60	theme	particular	915:924	arg1	charge					926:931	particular charge and polarity combinations	915:957	charge	926:931	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	4	61	theme	N-glycosylation	1110:1124	arg1	process					1126:1132	the N-glycosylation process	1106:1132	the N-glycosylation process	1106:1132	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	2	62	theme	amino	560:564	arg1	acids					566:570	both penultimate and vicinal amino acids	531:570	both penultimate and vicinal amino acids	531:570	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	0	63	theme	Carcinoma	157:165	arg1	Cells					167:171	Carcinoma Cells	157:171	Carcinoma Cells	157:171	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	2	64	theme	asparagine-based	580:595	arg1	N-glycosylation					612:626	the asparagine-based, site-specific N-glycosylation	576:626	the asparagine-based, site-specific N-glycosylation	576:626	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	2	65	used	utilized	389:396	arg2	we					386:387	we	386:387	we	386:387	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	5	66	theme	constitutive	1293:1304	arg1	glycosylation					1306:1318	constitutive glycosylation	1293:1318	constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition	1293:1494	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	0	67	theme	In	67:68	arg1	Study					77:81	A Genome-Wide In Silico Study	53:81	A Genome-Wide In Silico Study	53:81	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	3	68	theme	N-glycosylation	790:804	arg1	process					806:812	the N-glycosylation process	786:812	the N-glycosylation process	786:812	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	1	69	theme	proteins	361:368	arg1	properties					309:318	the individual properties	294:318	the individual properties of extracellular and membrane-associated proteins	294:368	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	6	70	theme	polarity-based	1607:1620	arg1	constraints					1634:1644	polarity-based mechanistic constraints	1607:1644	polarity-based mechanistic constraints in N-glycosylation	1607:1663	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	5	71	theme	epitope	1273:1279	arg1	vicinity					1246:1253	the vicinity	1242:1253	the vicinity of Asn-containing epitope	1242:1279	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	3	72	theme	NetNGlyc	831:838	arg1	predictions					840:850	NetNGlyc predictions	831:850	NetNGlyc predictions	831:850	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	3	73	theme	human	881:885	arg1	proteins					887:894	130 literature-reported human proteins	857:894	130 literature-reported human proteins	857:894	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	6	74	theme	phenotype	1708:1716	arg1	alterations					1678:1688	alterations	1678:1688	alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites	1678:1793	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	4	75	theme	non-polar	962:970	arg1	chain					1022:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain	962:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	3	76	from	involvement	669:679	arg1	process					806:812	the N-glycosylation process	786:812	the N-glycosylation process	786:812	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	4	77	theme	aliphatic	972:980	arg1	chain					1022:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain	962:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	6	78	theme	current	1501:1507	arg1	mapping					1521:1527	The current genome-wide mapping	1497:1527	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues)	1497:1573	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	5	79	dep	proteins	1400:1407	arg1	triggering					1448:1457	triggering	1448:1457	triggering epithelial-to-mesenchymal transition	1448:1494	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	79	dep	proteins	1400:1407	arg1	causing					1409:1415	causing	1409:1415	causing constitutive proliferation	1409:1442	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	4	80	theme	side	1017:1020	arg1	chain					1022:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain	962:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	0	81	dep	In	67:68	arg1	Silico					70:75	Silico	70:75	Silico	70:75	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	2	82	theme	based	449:453	arg1	mapping					467:473	in silico based genome-wide mapping	439:473	in silico based genome-wide mapping of 1,117 human proteins	439:497	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	3	83	theme	polarity	695:702	arg1	environment					704:714	polarity environment	695:714	polarity environment	695:714	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	2	84	theme	in	439:440	arg1	mapping					467:473	in silico based genome-wide mapping	439:473	in silico based genome-wide mapping of 1,117 human proteins	439:497	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	1	85	theme	individual	298:307	arg1	properties					309:318	the individual properties	294:318	the individual properties of extracellular and membrane-associated proteins	294:368	The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins.
29541627	2	86	theme	proteins	490:497	arg1	mapping					467:473	in silico based genome-wide mapping	439:473	in silico based genome-wide mapping of 1,117 human proteins	439:497	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	5	87	gly	glycosylation	1306:1318	arg1	proteins					1400:1407	membrane proteins	1391:1407	membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition	1391:1494	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	88	theme	membrane	1391:1398	arg1	proteins					1400:1407	membrane proteins	1391:1407	membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition	1391:1494	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	2	89	dep	asparagine-based	580:595	arg1	site-specific					598:610	site-specific	598:610	site-specific	598:610	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	4	90	theme	aromatic	1002:1009	arg1	chain					1022:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain	962:1026	non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids	962:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	3	91	theme	amino	730:734	arg1	acids					736:740	classified amino acids	719:740	classified amino acids (designated as L, O, A, P, and N groups)	719:781	Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins.
29541627	2	92	dep	in	439:440	arg1	silico					442:447	silico	442:447	silico	442:447	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29541627	6	93	theme	asparagine	1554:1563	arg1	residues					1565:1572	2,909 asparagine residues	1548:1572	2,909 asparagine residues	1548:1572	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	6	93	theme	asparagine	1554:1563	arg1	proteins					1538:1545	1,117 proteins	1532:1545	1,117 proteins (2,909 asparagine residues)	1532:1573	The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
29541627	5	94	theme	side-chain	1162:1171	arg1	charge					1173:1178	side-chain charge	1162:1178	side-chain charge	1162:1178	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	0	95	dep	Preferences	20:30	arg1	Study					77:81	A Genome-Wide In Silico Study	53:81	A Genome-Wide In Silico Study	53:81	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	0	95	dep	Preferences	20:30	arg1	Implications					91:102	Its Implications	87:102	Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells	87:171	Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells.
29541627	4	96	theme	amino	1072:1076	arg1	acids					1078:1082	both penultimate and vicinal amino acids	1043:1082	both penultimate and vicinal amino acids	1043:1082	From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the N-glycosylation process.
29541627	5	97	theme	non-preferred	1367:1379	arg1	sites					1381:1385	preferred and non-preferred sites	1353:1385	preferred and non-preferred sites	1353:1385	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	5	98	theme	preferred	1353:1361	arg1	sites					1381:1385	preferred and non-preferred sites	1353:1385	preferred and non-preferred sites	1353:1385	However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition.
29541627	2	99	theme	computational	408:420	arg1	tools					422:426	different computational tools	398:426	different computational tools	398:426	In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation.
29688431	1	0	theme	post-translational	158:175	arg1	N-acetyl-β-d-glucosamine					109:132	O-linked N-acetyl-β-d-glucosamine	100:132	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc)	100:143	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	1	0	theme	post-translational	158:175	arg1	modification					177:188	a dynamic post-translational modification	148:188	a dynamic post-translational modification that modifies thousands of proteins	148:224	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	6	1	used	used	856:859	arg2	it					846:847	it	846:847	it	846:847	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	2	2	theme	reasons	344:350	arg1	one					328:330	one	328:330	one	328:330	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	2	2	theme	reasons	344:350	arg1	lack					368:371	the lack	364:371	the lack of site-specific anti-O-GlcNAc antibodies	364:413	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	2	2	theme	reasons	344:350	arg1	reasons					344:350	the main reasons	335:350	the main reasons for this	335:359	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	3	3	from	site	523:526	arg1	O-GlcNAcylated					490:503	O-GlcNAcylated	490:503	O-GlcNAcylated	490:503	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	5	4	theme	site-specific	687:699	arg1	antibody					701:708	a site-specific antibody	685:708	a site-specific antibody	685:708	Here, we describe a site-specific antibody for SIRT1 O-GlcNAcylated at S549, named SIRT1-549-O.
29688431	7	5	theme	O-GlcNAcylation	1047:1061	arg1	roles					1032:1036	the roles	1028:1036	the roles of SIRT1 O-GlcNAcylation	1028:1061	Therefore, this antibody not only provides an effective method to further understand the roles of SIRT1 O-GlcNAcylation but also makes it possible to discover the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation.
29688431	3	6	theme	serine	512:517	arg1	site					523:526	the serine 549 site	508:526	the serine 549 site (S549)	508:533	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	3	6	theme	serine	512:517	arg1	S549					529:532	S549	529:532	S549	529:532	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	2	7	theme	site-specific	376:388	arg1	antibodies					404:413	site-specific anti-O-GlcNAc antibodies	376:413	site-specific anti-O-GlcNAc antibodies	376:413	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	3	8	theme	549	519:521	arg1	site					523:526	the serine 549 site	508:526	the serine 549 site (S549)	508:533	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	3	8	theme	549	519:521	arg1	S549					529:532	S549	529:532	S549	529:532	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	5	9	theme	O-GlcNAcylated	720:733	arg1	SIRT1					714:718	SIRT1	714:718	SIRT1 O-GlcNAcylated at S549	714:741	Here, we describe a site-specific antibody for SIRT1 O-GlcNAcylated at S549, named SIRT1-549-O.
29688431	4	10	theme	O-GlcNAcylation	634:648	arg1	roles					619:623	the roles	615:623	the roles of SIRT1 O-GlcNAcylation	615:648	However, the mechanism underlying the roles of SIRT1 O-GlcNAcylation remains unclear.
29688431	7	11	theme	SIRT1	1041:1045	arg1	O-GlcNAcylation					1047:1061	SIRT1 O-GlcNAcylation	1041:1061	SIRT1 O-GlcNAcylation	1041:1061	Therefore, this antibody not only provides an effective method to further understand the roles of SIRT1 O-GlcNAcylation but also makes it possible to discover the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation.
29688431	6	12	theme	western	817:823	arg1	blotting					825:832	western blotting	817:832	western blotting	817:832	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	4	13	theme	SIRT1	628:632	arg1	O-GlcNAcylation					634:648	SIRT1 O-GlcNAcylation	628:648	SIRT1 O-GlcNAcylation	628:648	However, the mechanism underlying the roles of SIRT1 O-GlcNAcylation remains unclear.
29688431	6	14	theme	SIRT1	920:924	arg1	O-GlcNAcylation					926:940	SIRT1 O-GlcNAcylation	920:940	SIRT1 O-GlcNAcylation	920:940	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	1	15	theme	O-linked	100:107	arg1	modification					177:188	a dynamic post-translational modification	148:188	a dynamic post-translational modification that modifies thousands of proteins	148:224	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	1	15	theme	O-linked	100:107	arg1	O-GlcNAc					135:142	O-GlcNAc	135:142	O-GlcNAc	135:142	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	1	15	theme	O-linked	100:107	arg1	N-acetyl-β-d-glucosamine					109:132	O-linked N-acetyl-β-d-glucosamine	100:132	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc)	100:143	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	2	16	dep	roles	240:244	arg1	the					236:238	the	236:238	the	236:238	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	7	17	theme	pharmacological	1118:1132	arg1	factors					1134:1140	the genetic and pharmacological factors	1102:1140	the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation	1102:1209	Therefore, this antibody not only provides an effective method to further understand the roles of SIRT1 O-GlcNAcylation but also makes it possible to discover the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation.
29688431	6	18	theme	mouse	914:918	arg1	levels					889:894	the endogenous levels	874:894	the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation	874:940	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	0	19	from	serine	88:93	arg1	O-GlcNAcylated					70:83	O-GlcNAcylated	70:83	O-GlcNAcylated	70:83	Generation and characterization of a site-specific antibody for SIRT1 O-GlcNAcylated at serine 549.
29688431	0	20	theme	site-specific	37:49	arg1	antibody					51:58	a site-specific antibody	35:58	a site-specific antibody	35:58	Generation and characterization of a site-specific antibody for SIRT1 O-GlcNAcylated at serine 549.
29688431	2	21	theme	antibodies	404:413	arg1	one					328:330	one	328:330	one	328:330	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	2	21	theme	antibodies	404:413	arg1	lack					368:371	the lack	364:371	the lack of site-specific anti-O-GlcNAc antibodies	364:413	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	2	21	theme	antibodies	404:413	arg1	reasons					344:350	the main reasons	335:350	the main reasons for this	335:359	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	7	22	theme	genetic	1106:1112	arg1	factors					1134:1140	the genetic and pharmacological factors	1102:1140	the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation	1102:1209	Therefore, this antibody not only provides an effective method to further understand the roles of SIRT1 O-GlcNAcylation but also makes it possible to discover the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation.
29688431	6	23	theme	human	904:908	arg1	levels					889:894	the endogenous levels	874:894	the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation	874:940	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	6	24	dep	human	904:908	arg1	O-GlcNAcylation					926:940	SIRT1 O-GlcNAcylation	920:940	SIRT1 O-GlcNAcylation	920:940	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	2	25	theme	anti-O-GlcNAc	390:402	arg1	antibodies					404:413	site-specific anti-O-GlcNAc antibodies	376:413	site-specific anti-O-GlcNAc antibodies	376:413	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	7	26	theme	SIRT1	1162:1166	arg1	activity					1168:1175	SIRT1 activity	1162:1175	SIRT1 activity	1162:1175	Therefore, this antibody not only provides an effective method to further understand the roles of SIRT1 O-GlcNAcylation but also makes it possible to discover the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation.
29688431	6	27	theme	blotting	825:832	arg1	assays					834:839	immunoprecipitation and western blotting assays	793:839	immunoprecipitation and western blotting assays	793:839	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	2	28	theme	main	339:342	arg1	reasons					344:350	the main reasons	335:350	the main reasons for this	335:359	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	0	29	theme	antibody	51:58	arg1	characterization					15:30	characterization	15:30	characterization	15:30	Generation and characterization of a site-specific antibody for SIRT1 O-GlcNAcylated at serine 549.
29688431	0	29	theme	antibody	51:58	arg1	Generation					0:9	Generation	0:9	Generation	0:9	Generation and characterization of a site-specific antibody for SIRT1 O-GlcNAcylated at serine 549.
29688431	5	30	from	S549	738:741	arg1	O-GlcNAcylated					720:733	O-GlcNAcylated	720:733	O-GlcNAcylated	720:733	Here, we describe a site-specific antibody for SIRT1 O-GlcNAcylated at S549, named SIRT1-549-O.
29688431	3	31	theme	cytoprotective	547:560	arg1	role					562:565	a cytoprotective role	545:565	a cytoprotective role	545:565	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	7	32	theme	effective	989:997	arg1	method					999:1004	an effective method	986:1004	an effective method to further understand the roles of SIRT1 O-GlcNAcylation	986:1061	Therefore, this antibody not only provides an effective method to further understand the roles of SIRT1 O-GlcNAcylation but also makes it possible to discover the genetic and pharmacological factors that could regulate SIRT1 activity by modulating its O-GlcNAcylation.
29688431	6	33	theme	immunoprecipitation	793:811	arg1	assays					834:839	immunoprecipitation and western blotting assays	793:839	immunoprecipitation and western blotting assays	793:839	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	3	34	theme	NAD+-dependent	459:472	arg1	deacetylase					474:484	an NAD+-dependent deacetylase	456:484	an NAD+-dependent deacetylase	456:484	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	3	34	theme	NAD+-dependent	459:472	arg1	SIRT1					440:444	SIRT1	440:444	SIRT1	440:444	Recently, we found that SIRT1, which is an NAD+-dependent deacetylase, is O-GlcNAcylated at the serine 549 site (S549) and plays a cytoprotective role under stress.
29688431	1	35	link	O-linked	100:107	arg1	modification					177:188	a dynamic post-translational modification	148:188	a dynamic post-translational modification that modifies thousands of proteins	148:224	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	1	35	link	O-linked	100:107	arg1	O-GlcNAc					135:142	O-GlcNAc	135:142	O-GlcNAc	135:142	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	1	35	link	O-linked	100:107	arg1	N-acetyl-β-d-glucosamine					109:132	O-linked N-acetyl-β-d-glucosamine	100:132	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc)	100:143	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	6	36	used	used	784:787	arg2	antibody					768:775	This antibody	763:775	This antibody	763:775	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	2	37	theme	O-GlcNAcylation	264:278	arg1	mechanisms					250:259	mechanisms	250:259	mechanisms	250:259	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	2	37	theme	O-GlcNAcylation	264:278	arg1	roles					240:244	roles	240:244	roles	240:244	However, the roles and mechanisms of O-GlcNAcylation have been clarified in only a few proteins, and one of the main reasons for this is the lack of site-specific anti-O-GlcNAc antibodies.
29688431	1	38	theme	proteins	217:224	arg1	thousands					204:212	thousands	204:212	thousands of proteins	204:224	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	6	39	theme	endogenous	878:887	arg1	levels					889:894	the endogenous levels	874:894	the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation	874:940	This antibody can be used for immunoprecipitation and western blotting assays, and it can be used to recognize the endogenous levels of both human and mouse SIRT1 O-GlcNAcylation.
29688431	1	40	theme	dynamic	150:156	arg1	N-acetyl-β-d-glucosamine					109:132	O-linked N-acetyl-β-d-glucosamine	100:132	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc)	100:143	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
29688431	1	40	theme	dynamic	150:156	arg1	modification					177:188	a dynamic post-translational modification	148:188	a dynamic post-translational modification that modifies thousands of proteins	148:224	O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies thousands of proteins.
30127001	9	0	theme	O-fucose	1554:1561	arg1	mutations					1563:1571	sensitizing O-fucose mutations	1542:1571	sensitizing O-fucose mutations in EGF8 or EGF12	1542:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	6	1	from	residue	1043:1049	arg1	location					1063:1070	the same location	1054:1070	the same location	1054:1070	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	6	2	theme	serine	1036:1041	arg1	residue					1043:1049	a serine residue	1034:1049	a serine residue in the same location	1034:1070	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	3	3	from	those	526:530	arg1	distinct					512:519	distinct	512:519	distinct	512:519	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	9	4	theme	site	1495:1498	arg1	Mutation					1460:1467	Mutation	1460:1467	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12	1460:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	5	with	combination	1525:1535	arg1	mutations					1563:1571	sensitizing O-fucose mutations	1542:1571	sensitizing O-fucose mutations in EGF8 or EGF12	1542:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	8	6	theme	acceptor	1399:1406	arg1	specificities					1408:1420	distinct acceptor specificities	1390:1420	distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10	1390:1457	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	5	7	theme	HEK293T	873:879	arg1	cells					881:885	HEK293T cells	873:885	HEK293T cells lacking POGLUT2, POGLUT3, or both genes	873:925	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes showed that either POGLUT2 or POGLUT3 can add this novel O-Glc modification.
30127001	9	8	from	Mutation	1460:1467	arg1	combination					1525:1535	combination	1525:1535	combination with sensitizing O-fucose mutations in EGF8 or EGF12	1525:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	8	from	Mutation	1460:1467	arg1	serine					1510:1515	serine 435	1510:1519	serine 435	1510:1519	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	8	from	Mutation	1460:1467	arg1	EGF11					1503:1507	EGF11	1503:1507	EGF11 (serine 435)	1503:1520	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	6	9	contain	have	1029:1032	arg1	EGF11					1004:1008	EGF11	1004:1008	EGF11 of NOTCH2	1004:1018	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	6	9	contain	have	1029:1032	arg2	residue					1043:1049	a serine residue	1034:1049	a serine residue in the same location	1034:1070	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	6	10	theme	same	1181:1184	arg1	position					1186:1193	the same position	1177:1193	the same position	1177:1193	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	2	11	theme	mammalian	307:315	arg1	domain					344:349	the mammalian NOTCH1 core ligand-binding domain	303:349	the mammalian NOTCH1 core ligand-binding domain	303:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	4	12	dep	POGLUT2	698:704	arg1	KDELC2					739:744	KDELC2	739:744	KDELC2	739:744	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	4	12	dep	POGLUT2	698:704	arg1	KDELC1					728:733	formerly KDELC1	719:733	formerly KDELC1	719:733	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	8	13	with	assays	1277:1282	arg1	POGLUT3					1301:1307	POGLUT3	1301:1307	POGLUT3	1301:1307	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	8	13	with	assays	1277:1282	arg1	POGLUT2					1289:1295	POGLUT2	1289:1295	POGLUT2	1289:1295	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	0	14	theme	Notch	92:96	arg1	trafficking					98:108	Notch trafficking	92:108	Notch trafficking	92:108	Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling.
30127001	8	15	theme	NOTCH3	1446:1451	arg1	EGF10					1453:1457	NOTCH3 EGF10	1446:1457	NOTCH3 EGF10	1446:1457	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	6	16	theme	NOTCH3	1111:1116	arg1	EGF10					1102:1106	EGF10	1102:1106	EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2)	1102:1155	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	9	17	from	EGF11	1503:1507	arg1	Mutation					1460:1467	Mutation	1460:1467	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12	1460:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	5	18	theme	Mass	823:826	arg1	analysis					842:849	Mass spectrometric analysis	823:849	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes	823:925	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes showed that either POGLUT2 or POGLUT3 can add this novel O-Glc modification.
30127001	7	19	theme	sites	1214:1218	arg1	Comparison					1196:1205	Comparison	1196:1205	Comparison of the sites	1196:1218	Comparison of the sites suggests a consensus sequence for modification.
30127001	8	20	theme	In	1268:1269	arg1	assays					1277:1282	In vitro assays	1268:1282	In vitro assays with POGLUT2 and POGLUT3	1268:1307	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	1	21	theme	Notch-ligand	178:189	arg1	interactions					191:202	Notch-ligand interactions	178:202	Notch-ligand interactions	178:202	The Notch-signaling pathway is normally activated by Notch-ligand interactions.
30127001	6	22	from	EGF11	1133:1137	arg1	-2					1153:1154	-2	1153:1154	-2	1153:1154	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	6	22	from	EGF11	1133:1137	arg1	NOTCH1					1142:1147	NOTCH1	1142:1147	NOTCH1	1142:1147	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	3	23	dep	cysteines	428:436	arg1	4					444:444	4	444:444	4	444:444	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	3	23	dep	cysteines	428:436	arg1	3					438:438	3	438:438	3	438:438	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	9	24	theme	O-Glc	1476:1480	arg1	site					1495:1498	the O-Glc modification site	1472:1498	the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12	1472:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	3	25	theme	Growth	459:464	arg1	repeat					484:489	Epidermal Growth Factor-like (EGF) repeat 11	449:492	Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	449:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	0	26	theme	novel	4:8	arg1	O-glucosyltransferases					18:39	Two novel protein O-glucosyltransferases	0:39	Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling	0:122	Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling.
30127001	2	27	theme	domain	344:349	arg1	modification					273:284	a novel O-linked hexose modification	249:284	a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain	249:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	9	28	from	combination	1525:1535	arg1	Mutation					1460:1467	Mutation	1460:1467	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12	1460:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	29	theme	modification	1482:1493	arg1	site					1495:1498	the O-Glc modification site	1472:1498	the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12	1472:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	8	30	theme	distinct	1390:1397	arg1	specificities					1408:1420	distinct acceptor specificities	1390:1420	distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10	1390:1457	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	2	31	theme	ligand-binding	329:342	arg1	domain					344:349	the mammalian NOTCH1 core ligand-binding domain	303:349	the mammalian NOTCH1 core ligand-binding domain	303:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	2	32	from	modification	273:284	arg1	serine					289:294	serine 435	289:298	serine 435	289:298	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	6	33	theme	NOTCH2	1013:1018	arg1	EGF11					1004:1008	EGF11	1004:1008	EGF11 of NOTCH2	1004:1018	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	4	34	theme	formerly	719:726	arg1	KDELC1					728:733	formerly KDELC1	719:733	formerly KDELC1	719:733	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	8	35	dep	In	1268:1269	arg1	vitro					1271:1275	vitro	1271:1275	vitro	1271:1275	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	2	36	theme	core	324:327	arg1	domain					344:349	the mammalian NOTCH1 core ligand-binding domain	303:349	the mammalian NOTCH1 core ligand-binding domain	303:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	3	37	theme	EGF	479:481	arg1	repeat					484:489	Epidermal Growth Factor-like (EGF) repeat 11	449:492	Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	449:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	0	38	theme	protein	10:16	arg1	O-glucosyltransferases					18:39	Two novel protein O-glucosyltransferases	0:39	Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling	0:122	Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling.
30127001	8	39	theme	folded	1357:1362	arg1	repeats					1368:1374	only properly folded EGF repeats	1343:1374	only properly folded EGF repeats	1343:1374	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	2	40	theme	NOTCH1	317:322	arg1	domain					344:349	the mammalian NOTCH1 core ligand-binding domain	303:349	the mammalian NOTCH1 core ligand-binding domain	303:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	5	41	theme	NOTCH1	854:859	arg1	analysis					842:849	Mass spectrometric analysis	823:849	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes	823:925	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes showed that either POGLUT2 or POGLUT3 can add this novel O-Glc modification.
30127001	3	42	theme	NOTCH1	497:502	arg1	repeat					484:489	Epidermal Growth Factor-like (EGF) repeat 11	449:492	Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	449:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	9	43	theme	NOTCH1	1628:1633	arg1	activation					1646:1655	reduced activation	1638:1655	reduced activation of NOTCH1	1638:1665	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	43	theme	NOTCH1	1628:1633	arg1	presentation					1612:1623	cell-surface presentation	1599:1623	cell-surface presentation of NOTCH1	1599:1633	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	44	theme	cell-surface	1599:1610	arg1	presentation					1612:1623	cell-surface presentation	1599:1623	cell-surface presentation of NOTCH1	1599:1633	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	2	45	theme	O-linked	257:264	arg1	modification					273:284	a novel O-linked hexose modification	249:284	a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain	249:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	9	46	from	site	1495:1498	arg1	combination					1525:1535	combination	1525:1535	combination with sensitizing O-fucose mutations in EGF8 or EGF12	1525:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	46	from	site	1495:1498	arg1	serine					1510:1515	serine 435	1510:1519	serine 435	1510:1519	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	46	from	site	1495:1498	arg1	EGF11					1503:1507	EGF11	1503:1507	EGF11 (serine 435)	1503:1520	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	3	47	theme	Factor-like	466:476	arg1	repeat					484:489	Epidermal Growth Factor-like (EGF) repeat 11	449:492	Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	449:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	3	48	theme	Epidermal	449:457	arg1	repeat					484:489	Epidermal Growth Factor-like (EGF) repeat 11	449:492	Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	449:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	2	49	with	interface	363:371	arg1	ligands					382:388	its ligands	378:388	its ligands	378:388	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	2	50	theme	novel	251:255	arg1	modification					273:284	a novel O-linked hexose modification	249:284	a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain	249:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	9	51	from	mutations	1563:1571	arg1	EGF12					1584:1588	EGF12	1584:1588	EGF12	1584:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	51	from	mutations	1563:1571	arg1	EGF8					1576:1579	EGF8	1576:1579	EGF8	1576:1579	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	0	52	theme	distinct	59:66	arg1	sites					53:57	sites	53:57	sites distinct from POGLUT1	53:79	Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling.
30127001	9	53	theme	reduced	1638:1644	arg1	activation					1646:1655	reduced activation	1638:1655	reduced activation of NOTCH1	1638:1665	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	8	54	theme	EGF	1364:1366	arg1	repeats					1368:1374	only properly folded EGF repeats	1343:1374	only properly folded EGF repeats	1343:1374	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	5	55	theme	novel	978:982	arg1	modification					990:1001	this novel O-Glc modification	973:1001	this novel O-Glc modification	973:1001	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes showed that either POGLUT2 or POGLUT3 can add this novel O-Glc modification.
30127001	6	56	theme	same	1058:1061	arg1	location					1063:1070	the same location	1054:1070	the same location	1054:1070	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	8	57	theme	NOTCH1	1429:1434	arg1	EGF11					1436:1440	NOTCH1 EGF11	1429:1440	NOTCH1 EGF11	1429:1440	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	10	58	theme	Notch-signaling	1774:1788	arg1	pathway					1790:1796	the Notch-signaling pathway	1770:1796	the Notch-signaling pathway in mammals	1770:1807	This study identifies a previously undescribed mechanism for fine-tuning the Notch-signaling pathway in mammals.
30127001	5	59	theme	O-Glc	984:988	arg1	modification					990:1001	this novel O-Glc modification	973:1001	this novel O-Glc modification	973:1001	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes showed that either POGLUT2 or POGLUT3 can add this novel O-Glc modification.
30127001	0	60	from	POGLUT1	73:79	arg1	distinct					59:66	distinct	59:66	distinct	59:66	Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling.
30127001	10	61	from	pathway	1790:1796	arg1	mammals					1801:1807	mammals	1801:1807	mammals	1801:1807	This study identifies a previously undescribed mechanism for fine-tuning the Notch-signaling pathway in mammals.
30127001	6	62	theme	homologous	1119:1128	arg1	NOTCH3					1111:1116	NOTCH3	1111:1116	NOTCH3 (homologous to EGF11 in NOTCH1 and -2)	1111:1155	EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position.
30127001	7	63	theme	consensus	1231:1239	arg1	sequence					1241:1248	a consensus sequence	1229:1248	a consensus sequence for modification	1229:1265	Comparison of the sites suggests a consensus sequence for modification.
30127001	3	64	theme	different	605:613	arg1	responsible					625:635	responsible	625:635	responsible	625:635	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	3	64	theme	different	605:613	arg1	enzyme					615:620	a different enzyme	603:620	a different enzyme	603:620	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	9	65	theme	sensitizing	1542:1552	arg1	mutations					1563:1571	sensitizing O-fucose mutations	1542:1571	sensitizing O-fucose mutations in EGF8 or EGF12	1542:1588	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	1	66	theme	Notch-signaling	129:143	arg1	pathway					145:151	The Notch-signaling pathway	125:151	The Notch-signaling pathway	125:151	The Notch-signaling pathway is normally activated by Notch-ligand interactions.
30127001	3	67	theme	protein	544:550	arg1	O-glucosyltransferase					552:572	protein O-glucosyltransferase 1	544:574	protein O-glucosyltransferase 1 (POGLUT1)	544:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	3	67	theme	protein	544:550	arg1	POGLUT1					577:583	POGLUT1	577:583	POGLUT1	577:583	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	9	68	theme	NOTCH1	1660:1665	arg1	activation					1646:1655	reduced activation	1638:1655	reduced activation of NOTCH1	1638:1665	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	9	68	theme	NOTCH1	1660:1665	arg1	presentation					1612:1623	cell-surface presentation	1599:1623	cell-surface presentation of NOTCH1	1599:1633	Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively.
30127001	2	69	theme	structural	214:223	arg1	analysis					225:232	A recent structural analysis	205:232	A recent structural analysis	205:232	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	4	70	theme	novel	660:664	arg1	O-glucosyltransferases					674:695	two novel protein O-glucosyltransferases	656:695	two novel protein O-glucosyltransferases	656:695	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	4	70	theme	novel	660:664	arg1	POGLUT3					710:716	POGLUT3	710:716	POGLUT3	710:716	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	4	70	theme	novel	660:664	arg1	POGLUT2					698:704	POGLUT2	698:704	POGLUT2	698:704	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	3	71	theme	repeat	484:489	arg1	cysteines					428:436	conserved cysteines 3 and 4	418:444	conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	418:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	2	72	theme	recent	207:212	arg1	analysis					225:232	A recent structural analysis	205:232	A recent structural analysis	205:232	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	8	73	theme	only	1343:1346	arg1	repeats					1368:1374	only properly folded EGF repeats	1343:1374	only properly folded EGF repeats	1343:1374	In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10.
30127001	2	74	mod	modification	273:284	arg3	hexose					266:271	a novel O-linked hexose modification	249:284	a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain	249:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	2	74	mod	modification	273:284	arg1	domain					344:349	the mammalian NOTCH1 core ligand-binding domain	303:349	the mammalian NOTCH1 core ligand-binding domain	303:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	4	75	theme	protein	666:672	arg1	O-glucosyltransferases					674:695	two novel protein O-glucosyltransferases	656:695	two novel protein O-glucosyltransferases	656:695	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	4	75	theme	protein	666:672	arg1	POGLUT3					710:716	POGLUT3	710:716	POGLUT3	710:716	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	4	75	theme	protein	666:672	arg1	POGLUT2					698:704	POGLUT2	698:704	POGLUT2	698:704	Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435.
30127001	5	76	theme	spectrometric	828:840	arg1	analysis					842:849	Mass spectrometric analysis	823:849	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes	823:925	Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes showed that either POGLUT2 or POGLUT3 can add this novel O-Glc modification.
30127001	2	77	link	O-linked	257:264	arg1	modification					273:284	a novel O-linked hexose modification	249:284	a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain	249:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	3	78	theme	conserved	418:426	arg1	cysteines					428:436	conserved cysteines 3 and 4	418:444	conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	418:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	10	79	theme	undescribed	1732:1742	arg1	mechanism					1744:1752	a previously undescribed mechanism	1719:1752	a previously undescribed mechanism for fine-tuning the Notch-signaling pathway in mammals	1719:1807	This study identifies a previously undescribed mechanism for fine-tuning the Notch-signaling pathway in mammals.
30127001	2	80	theme	hexose	266:271	arg1	modification					273:284	a novel O-linked hexose modification	249:284	a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain	249:349	A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands.
30127001	3	81	theme	distinct	512:519	arg1	NOTCH1					497:502	NOTCH1	497:502	NOTCH1	497:502	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30127001	3	81	theme	distinct	512:519	arg1	site					507:510	a site	505:510	a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1)	505:584	This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible.
30143533	9	0	from	positions	1280:1288	arg1	residues					1268:1275	hydroxylysine residues	1254:1275	hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1254:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	5	1	with	tendons	655:661	arg1	stiffness					676:684	reduced stiffness	668:684	reduced stiffness	668:684	However, diabetic animal models have also displayed weakened tendons with reduced stiffness.
30143533	10	2	theme	oxidase	1465:1471	arg1	cross-linking					1484:1496	normal lysyl oxidase controlled cross-linking	1452:1496	normal lysyl oxidase controlled cross-linking in diabetic tendons	1452:1516	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	11	3	theme	normal	1575:1580	arg1	process					1596:1602	the normal cross-linking process	1571:1602	the normal cross-linking process	1571:1602	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	9	4	dep	positions	1280:1288	arg1	K87					1316:1318	α2(I)K87	1311:1318	α2(I)K87	1311:1318	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	4	dep	positions	1280:1288	arg1	K933					1329:1332	α2(I)K933	1324:1332	α2(I)K933	1324:1332	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	4	dep	positions	1280:1288	arg1	K87					1295:1297	α1(I)K87	1290:1297	α1(I)K87	1290:1297	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	4	dep	positions	1280:1288	arg1	positions					1280:1288	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933	1280:1332	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1280:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	4	dep	positions	1280:1288	arg1	K930					1305:1308	α1(I)K930	1300:1308	α1(I)K930	1300:1308	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	2	5	theme	impaired	292:299	arg1	tissues					301:307	impaired tissues	292:307	impaired tissues	292:307	How exactly such random glycations result in impaired tissues is still poorly understood.
30143533	7	6	theme	partial	867:873	arg1	glycations					899:908	partial fructosyl-hydroxylysine glycations	867:908	partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model	867:1034	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	9	7	theme	helix	1348:1352	arg1	K87					1316:1318	α2(I)K87	1311:1318	α2(I)K87	1311:1318	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	7	theme	helix	1348:1352	arg1	K933					1329:1332	α2(I)K933	1324:1332	α2(I)K933	1324:1332	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	7	theme	helix	1348:1352	arg1	K87					1295:1297	α1(I)K87	1290:1297	α1(I)K87	1290:1297	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	7	theme	helix	1348:1352	arg1	positions					1280:1288	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933	1280:1332	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1280:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	7	theme	helix	1348:1352	arg1	K930					1305:1308	α1(I)K930	1300:1308	α1(I)K930	1300:1308	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	10	8	theme	diabetic	1501:1508	arg1	tendons					1510:1516	diabetic tendons	1501:1516	diabetic tendons	1501:1516	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	5	9	theme	weakened	646:653	arg1	tendons					655:661	weakened tendons	646:661	weakened tendons with reduced stiffness	646:684	However, diabetic animal models have also displayed weakened tendons with reduced stiffness.
30143533	9	10	theme	lysine	1234:1239	arg1	aldehydes					1241:1249	telopeptide lysine aldehydes	1222:1249	telopeptide lysine aldehydes	1222:1249	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	7	11	theme	mass	829:832	arg1	spectrometry					834:845	targeted mass spectrometry	820:845	targeted mass spectrometry	820:845	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	1	12	theme	progressive	198:208	arg1	complications					220:232	the progressive secondary complications	194:232	the progressive secondary complications of diabetes	194:244	Non-enzymatic glycation of collagen has long been associated with the progressive secondary complications of diabetes.
30143533	9	13	dep	K933	1329:1332	arg1	I					1327:1327	I	1327:1327	I	1327:1327	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	7	14	from	model	1030:1034	arg1	tissues					1000:1006	tissues	1000:1006	tissues from a diabetic mouse model	1000:1034	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	7	15	theme	targeted	820:827	arg1	spectrometry					834:845	targeted mass spectrometry	820:845	targeted mass spectrometry	820:845	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	7	16	theme	diabetic	1015:1022	arg1	model					1030:1034	a diabetic mouse model	1013:1034	a diabetic mouse model	1013:1034	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	11	17	theme	tissue	1697:1702	arg1	properties					1713:1722	tissue material properties	1697:1722	tissue material properties	1697:1722	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	2	18	theme	random	264:269	arg1	glycations					271:280	exactly such random glycations	251:280	exactly such random glycations	251:280	How exactly such random glycations result in impaired tissues is still poorly understood.
30143533	1	19	theme	Non-enzymatic	128:140	arg1	glycation					142:150	Non-enzymatic glycation	128:150	Non-enzymatic glycation of collagen	128:162	Non-enzymatic glycation of collagen has long been associated with the progressive secondary complications of diabetes.
30143533	0	20	theme	same	53:56	arg1	sites					80:84	the same helical domain lysine sites	49:84	the same helical domain lysine sites	49:84	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	0	21	theme	domain	66:71	arg1	sites					80:84	the same helical domain lysine sites	49:84	the same helical domain lysine sites	49:84	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	3	22	theme	rate	366:369	arg1	susceptible					414:424	susceptible	414:424	susceptible	414:424	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	5	23	theme	animal	612:617	arg1	models					619:624	diabetic animal models	603:624	diabetic animal models	603:624	However, diabetic animal models have also displayed weakened tendons with reduced stiffness.
30143533	3	24	theme	slow	352:355	arg1	rate					366:369	the slow turnover rate	348:369	the slow turnover rate of most fibrillar collagens	348:397	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	7	25	from	each	913:916	arg1	glycations					899:908	partial fructosyl-hydroxylysine glycations	867:908	partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model	867:1034	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	7	26	theme	type	963:966	arg1	collagen					970:977	type I collagen	963:977	type I collagen	963:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	3	27	theme	collagens	389:397	arg1	rate					366:369	the slow turnover rate	348:369	the slow turnover rate of most fibrillar collagens	348:397	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	9	28	dep	K87	1316:1318	arg1	I					1314:1314	I	1314:1314	I	1314:1314	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	10	29	theme	site-specific	1376:1388	arg1	glycations					1390:1399	site-specific glycations	1376:1399	site-specific glycations of these specific lysines	1376:1425	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	9	30	theme	Type	1100:1103	arg1	collagen					1107:1114	Type I collagen	1100:1114	Type I collagen in mouse tendons	1100:1131	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	8	31	theme	other	1068:1072	arg1	residues					1090:1097	any other collagen lysine residues	1064:1097	any other collagen lysine residues	1064:1097	Glycation was not found at any other collagen lysine residues.
30143533	3	32	theme	most	374:377	arg1	collagens					389:397	most fibrillar collagens	374:397	most fibrillar collagens	374:397	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	7	33	theme	collagen	970:977	arg1	sites					954:958	the helical domain cross-linking sites	921:958	the helical domain cross-linking sites of type I collagen	921:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	7	33	theme	collagen	970:977	arg1	collagen					970:977	type I collagen	963:977	type I collagen	963:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	3	34	theme	subsequent	470:479	arg1	-products					509:517	subsequent advanced glycation end (AGE)-products	470:517	subsequent advanced glycation end (AGE)-products	470:517	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	0	35	theme	type	13:16	arg1	collagen					20:27	type I collagen	13:27	type I collagen	13:27	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	8	36	theme	lysine	1083:1088	arg1	residues					1090:1097	any other collagen lysine residues	1064:1097	any other collagen lysine residues	1064:1097	Glycation was not found at any other collagen lysine residues.
30143533	9	37	dep	K87	1295:1297	arg1	I					1293:1293	I	1293:1293	I	1293:1293	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	10	38	theme	specific	1410:1417	arg1	lysines					1419:1425	these specific lysines	1404:1425	these specific lysines	1404:1425	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	11	39	theme	mature	1649:1654	arg1	cross-links					1656:1666	mature cross-links	1649:1666	mature cross-links	1649:1666	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	9	40	theme	mouse	1119:1123	arg1	tendons					1125:1131	mouse tendons	1119:1131	mouse tendons	1119:1131	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	0	41	theme	collagen	20:27	arg1	Glycation					0:8	Glycation	0:8	Glycation of type I collagen	0:27	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	9	42	dep	K930	1305:1308	arg1	I					1303:1303	I	1303:1303	I	1303:1303	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	10	43	theme	lysyl	1459:1463	arg1	oxidase					1465:1471	normal lysyl oxidase	1452:1471	normal lysyl oxidase controlled cross-linking in diabetic tendons	1452:1516	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	11	44	theme	N-linked	1540:1547	arg1	glycations					1549:1558	such N-linked glycations	1535:1558	such N-linked glycations	1535:1558	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	6	45	theme	glycation	765:773	arg1	site					757:760	not a single experimentally identified specific molecular site	699:760	not a single experimentally identified specific molecular site of glycation in a collagen	699:787	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	6	45	theme	glycation	765:773	arg1	glycation					765:773	glycation	765:773	glycation	765:773	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	3	46	theme	glycation	490:498	arg1	-products					509:517	subsequent advanced glycation end (AGE)-products	470:517	subsequent advanced glycation end (AGE)-products	470:517	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	7	47	theme	cross-linking	940:952	arg1	sites					954:958	the helical domain cross-linking sites	921:958	the helical domain cross-linking sites of type I collagen	921:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	7	47	theme	cross-linking	940:952	arg1	collagen					970:977	type I collagen	963:977	type I collagen	963:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	9	48	theme	acid-labile	1169:1179	arg1	bonds					1190:1194	acid-labile aldimine bonds	1169:1194	acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1169:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	7	49	theme	helical	925:931	arg1	sites					954:958	the helical domain cross-linking sites	921:958	the helical domain cross-linking sites of type I collagen	921:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	7	49	theme	helical	925:931	arg1	collagen					970:977	type I collagen	963:977	type I collagen	963:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	10	50	theme	controlled	1473:1482	arg1	cross-linking					1484:1496	normal lysyl oxidase controlled cross-linking	1452:1496	normal lysyl oxidase controlled cross-linking in diabetic tendons	1452:1516	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	6	51	theme	specific	738:745	arg1	site					757:760	not a single experimentally identified specific molecular site	699:760	not a single experimentally identified specific molecular site of glycation in a collagen	699:787	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	6	51	theme	specific	738:745	arg1	glycation					765:773	glycation	765:773	glycation	765:773	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	6	52	from	site	757:760	arg1	collagen					780:787	a collagen	778:787	a collagen	778:787	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	4	53	theme	host	580:583	arg1	tissues					585:591	host tissues	580:591	host tissues	580:591	The latter are believed to include cross-links that stiffen host tissues.
30143533	11	54	theme	cross-linking	1582:1594	arg1	process					1596:1602	the normal cross-linking process	1571:1602	the normal cross-linking process	1571:1602	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	5	55	theme	reduced	668:674	arg1	stiffness					676:684	reduced stiffness	668:684	reduced stiffness	668:684	However, diabetic animal models have also displayed weakened tendons with reduced stiffness.
30143533	9	56	theme	triple	1341:1346	arg1	helix					1348:1352	the triple helix	1337:1352	the triple helix	1337:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	7	57	theme	fructosyl-hydroxylysine	875:897	arg1	glycations					899:908	partial fructosyl-hydroxylysine glycations	867:908	partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model	867:1034	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	9	58	theme	telopeptide	1222:1232	arg1	aldehydes					1241:1249	telopeptide lysine aldehydes	1222:1249	telopeptide lysine aldehydes	1222:1249	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	8	59	located	found	1055:1059	arg2	Glycation					1037:1045	Glycation	1037:1045	Glycation	1037:1045	Glycation was not found at any other collagen lysine residues.
30143533	8	59	located	found	1055:1059	arg1	residues					1090:1097	any other collagen lysine residues	1064:1097	any other collagen lysine residues	1064:1097	Glycation was not found at any other collagen lysine residues.
30143533	9	60	theme	aldehydes	1241:1249	arg1	addition					1210:1217	the addition	1206:1217	the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1206:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	61	theme	hydroxylysine	1254:1266	arg1	residues					1268:1275	hydroxylysine residues	1254:1275	hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1254:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	1	62	theme	secondary	210:218	arg1	complications					220:232	the progressive secondary complications	194:232	the progressive secondary complications of diabetes	194:244	Non-enzymatic glycation of collagen has long been associated with the progressive secondary complications of diabetes.
30143533	11	63	dep	content	1621:1627	arg1	the					1617:1619	the	1617:1619	the	1617:1619	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	11	64	link	N-linked	1540:1547	arg1	glycations					1549:1558	such N-linked glycations	1535:1558	such N-linked glycations	1535:1558	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	9	65	theme	α1	1290:1291	arg1	K87					1295:1297	α1(I)K87	1290:1297	α1(I)K87	1290:1297	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	65	theme	α1	1290:1291	arg1	positions					1280:1288	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933	1280:1332	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1280:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	7	66	theme	mouse	1024:1028	arg1	model					1030:1034	a diabetic mouse model	1013:1034	a diabetic mouse model	1013:1034	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	11	67	theme	material	1704:1711	arg1	properties					1713:1722	tissue material properties	1697:1722	tissue material properties	1697:1722	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	0	68	theme	helical	58:64	arg1	sites					80:84	the same helical domain lysine sites	49:84	the same helical domain lysine sites	49:84	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	2	69	theme	such	259:262	arg1	glycations					271:280	exactly such random glycations	251:280	exactly such random glycations	251:280	How exactly such random glycations result in impaired tissues is still poorly understood.
30143533	0	70	theme	lysine	73:78	arg1	sites					80:84	the same helical domain lysine sites	49:84	the same helical domain lysine sites	49:84	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	1	71	theme	collagen	155:162	arg1	glycation					142:150	Non-enzymatic glycation	128:150	Non-enzymatic glycation of collagen	128:162	Non-enzymatic glycation of collagen has long been associated with the progressive secondary complications of diabetes.
30143533	9	72	theme	α1	1300:1301	arg1	positions					1280:1288	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933	1280:1332	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1280:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	72	theme	α1	1300:1301	arg1	K930					1305:1308	α1(I)K930	1300:1308	α1(I)K930	1300:1308	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	5	73	theme	diabetic	603:610	arg1	models					619:624	diabetic animal models	603:624	diabetic animal models	603:624	However, diabetic animal models have also displayed weakened tendons with reduced stiffness.
30143533	0	74	dep	oxidase-	95:102	arg1	mediated					104:111	mediated	104:111	mediated	104:111	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	6	75	theme	identified	727:736	arg1	site					757:760	not a single experimentally identified specific molecular site	699:760	not a single experimentally identified specific molecular site of glycation in a collagen	699:787	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	6	75	theme	identified	727:736	arg1	glycation					765:773	glycation	765:773	glycation	765:773	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	0	76	theme	oxidase-	95:102	arg1	cross-linking					113:125	lysyl oxidase- mediated cross-linking	89:125	lysyl oxidase- mediated cross-linking	89:125	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	3	77	theme	turnover	357:364	arg1	rate					366:369	the slow turnover rate	348:369	the slow turnover rate of most fibrillar collagens	348:397	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	6	78	theme	single	705:710	arg1	site					757:760	not a single experimentally identified specific molecular site	699:760	not a single experimentally identified specific molecular site of glycation in a collagen	699:787	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	6	78	theme	single	705:710	arg1	glycation					765:773	glycation	765:773	glycation	765:773	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	3	79	theme	dependent	445:453	arg1	glycations					455:464	time dependent glycations	440:464	time dependent glycations	440:464	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	8	80	theme	collagen	1074:1081	arg1	residues					1090:1097	any other collagen lysine residues	1064:1097	any other collagen lysine residues	1064:1097	Glycation was not found at any other collagen lysine residues.
30143533	7	81	theme	I	968:968	arg1	collagen					970:977	type I collagen	963:977	type I collagen	963:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	9	82	theme	I	1105:1105	arg1	collagen					1107:1114	Type I collagen	1100:1114	Type I collagen in mouse tendons	1100:1131	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	0	83	theme	I	18:18	arg1	collagen					20:27	type I collagen	13:27	type I collagen	13:27	Glycation of type I collagen selectively targets the same helical domain lysine sites as lysyl oxidase- mediated cross-linking.
30143533	9	84	theme	α2	1311:1312	arg1	K87					1316:1318	α2(I)K87	1311:1318	α2(I)K87	1311:1318	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	84	theme	α2	1311:1312	arg1	positions					1280:1288	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933	1280:1332	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1280:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	3	85	theme	fibrillar	379:387	arg1	collagens					389:397	most fibrillar collagens	374:397	most fibrillar collagens	374:397	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	10	86	theme	lysines	1419:1425	arg1	glycations					1390:1399	site-specific glycations	1376:1399	site-specific glycations of these specific lysines	1376:1425	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	3	87	theme	advanced	481:488	arg1	-products					509:517	subsequent advanced glycation end (AGE)-products	470:517	subsequent advanced glycation end (AGE)-products	470:517	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	11	88	theme	such	1535:1538	arg1	glycations					1549:1558	such N-linked glycations	1535:1558	such N-linked glycations	1535:1558	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	10	89	from	cross-linking	1484:1496	arg1	tendons					1510:1516	diabetic tendons	1501:1516	diabetic tendons	1501:1516	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	10	90	theme	normal	1452:1457	arg1	oxidase					1465:1471	normal lysyl oxidase	1452:1471	normal lysyl oxidase controlled cross-linking in diabetic tendons	1452:1516	Our data reveal that site-specific glycations of these specific lysines may significantly impair normal lysyl oxidase controlled cross-linking in diabetic tendons.
30143533	9	91	from	collagen	1107:1114	arg1	tendons					1125:1131	mouse tendons	1119:1131	mouse tendons	1119:1131	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	3	92	theme	AGE	505:507	arg1	-products					509:517	subsequent advanced glycation end (AGE)-products	470:517	subsequent advanced glycation end (AGE)-products	470:517	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	7	93	theme	domain	933:938	arg1	sites					954:958	the helical domain cross-linking sites	921:958	the helical domain cross-linking sites of type I collagen	921:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	7	93	theme	domain	933:938	arg1	collagen					970:977	type I collagen	963:977	type I collagen	963:977	Here, using targeted mass spectrometry, we have identified partial fructosyl-hydroxylysine glycations at each of the helical domain cross-linking sites of type I collagen that are elevated in tissues from a diabetic mouse model.
30143533	9	94	theme	α2	1324:1325	arg1	K933					1329:1332	α2(I)K933	1324:1332	α2(I)K933	1324:1332	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	9	94	theme	α2	1324:1325	arg1	positions					1280:1288	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933	1280:1332	positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1280:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30143533	6	95	theme	molecular	747:755	arg1	site					757:760	not a single experimentally identified specific molecular site	699:760	not a single experimentally identified specific molecular site of glycation in a collagen	699:787	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	6	95	theme	molecular	747:755	arg1	glycation					765:773	glycation	765:773	glycation	765:773	Strikingly, not a single experimentally identified specific molecular site of glycation in a collagen has been reported.
30143533	11	96	theme	cross-links	1656:1666	arg1	content					1621:1627	content	1621:1627	content	1621:1627	We propose that such N-linked glycations can hinder the normal cross-linking process, so altering the content and/or placement of mature cross-links with the potential to modify tissue material properties.
30143533	3	97	theme	end	500:502	arg1	-products					509:517	subsequent advanced glycation end (AGE)-products	470:517	subsequent advanced glycation end (AGE)-products	470:517	Because of the slow turnover rate of most fibrillar collagens, they are more susceptible to accumulate time dependent glycations and subsequent advanced glycation end (AGE)-products.
30143533	1	98	theme	diabetes	237:244	arg1	complications					220:232	the progressive secondary complications	194:232	the progressive secondary complications of diabetes	194:244	Non-enzymatic glycation of collagen has long been associated with the progressive secondary complications of diabetes.
30143533	9	99	theme	aldimine	1181:1188	arg1	bonds					1190:1194	acid-labile aldimine bonds	1169:1194	acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix	1169:1352	Type I collagen in mouse tendons is cross-linked intermolecularly by acid-labile aldimine bonds formed by the addition of telopeptide lysine aldehydes to hydroxylysine residues at positions α1(I)K87, α1(I)K930, α2(I)K87 and α2(I)K933 of the triple helix.
30059200	4	0	theme	site-specific	745:757	arg1	manner					759:764	a site-specific manner	743:764	a site-specific manner	743:764	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	6	1	theme	O-GlcNAc	1121:1128	arg1	modification					1130:1141	O-GlcNAc modification	1121:1141	O-GlcNAc modification	1121:1141	The isoTCL platform provides a powerful tool for quantitative profiling of O-GlcNAc modification.
30059200	1	2	theme	modification	176:187	arg1	quantification					107:120	Large-scale quantification	95:120	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner	95:213	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	4	3	theme	sugar	624:628	arg1	donor					630:634	the sugar donor	620:634	the sugar donor	620:634	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	5	4	theme	O-GlcNAcylation	813:827	arg1	levels					843:848	the O-GlcNAcylation stoichiometry levels	809:848	the O-GlcNAcylation stoichiometry levels of more than 100 modification sites	809:884	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	3	5	theme	HeLa	544:547	arg1	cells					549:553	HeLa cells	544:553	HeLa cells	544:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	2	6	theme	linker	318:323	arg1	strategy					334:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	5	7	dep	confirmed	941:949	arg1	has					990:992	has	990:992	has a higher O-GlcNAcylation than its male counterpart	990:1043	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	5	8	theme	higher	996:1001	arg1	O-GlcNAcylation					1003:1017	a higher O-GlcNAcylation	994:1017	a higher O-GlcNAcylation than its male counterpart	994:1043	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	3	9	from	cells	549:553	arg1	quantification					501:514	quantification	501:514	quantification	501:514	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	3	9	from	cells	549:553	arg1	mapping					489:495	mapping	489:495	mapping	489:495	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	2	10	theme	cleavable	308:316	arg1	strategy					334:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	5	11	theme	male	916:919	arg1	mice					932:935	male and female mice	916:935	male and female mice	916:935	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	2	12	theme	isotopic	358:365	arg1	labeling					367:374	isotopic labeling	358:374	isotopic labeling of O-GlcNAc	358:386	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	5	13	theme	placenta	894:901	arg1	samples					903:909	placenta samples	894:909	placenta samples from male and female mice	894:935	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	4	14	theme	modification	665:676	arg1	levels					655:660	the levels	651:660	the levels of modification	651:676	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	2	15	theme	isotope-tagged	293:306	arg1	strategy					334:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	5	16	theme	female	925:930	arg1	mice					932:935	male and female mice	916:935	male and female mice	916:935	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	2	17	theme	affinity	425:432	arg1	tags					434:437	affinity tags	425:437	affinity tags	425:437	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	6	18	theme	isoTCL	1050:1055	arg1	platform					1057:1064	The isoTCL platform	1046:1064	The isoTCL platform	1046:1064	The isoTCL platform provides a powerful tool for quantitative profiling of O-GlcNAc modification.
30059200	5	19	theme	stoichiometry	829:841	arg1	levels					843:848	the O-GlcNAcylation stoichiometry levels	809:848	the O-GlcNAcylation stoichiometry levels of more than 100 modification sites	809:884	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	3	20	from	quantification	501:514	arg1	cells					549:553	HeLa cells	544:553	HeLa cells	544:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	3	20	from	quantification	501:514	arg1	application					460:470	the application	456:470	the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells	456:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	3	21	theme	O-GlcNAcylation	519:533	arg1	sites					535:539	O-GlcNAcylation sites	519:539	O-GlcNAcylation sites in HeLa cells	519:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	1	22	theme	site-specific	194:206	arg1	manner					208:213	a site-specific manner	192:213	a site-specific manner	192:213	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	23	theme	Large-scale	95:105	arg1	quantification					107:120	Large-scale quantification	95:120	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner	95:213	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	4	24	theme	labeling	725:732	arg1	probe					734:738	the O-GlcNAc labeling probe	712:738	the O-GlcNAc labeling probe	712:738	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	0	25	theme	Quantitative	0:11	arg1	Profiling					13:21	Quantitative Profiling	0:21	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker	0:92	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker.
30059200	4	26	theme	O-GlcNAcylation	589:603	arg1	sensitivity					605:615	the O-GlcNAcylation sensitivity	585:615	the O-GlcNAcylation sensitivity to the sugar donor	585:634	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	2	27	theme	bioorthogonal	396:408	arg1	conjugation					410:420	bioorthogonal conjugation	396:420	bioorthogonal conjugation of affinity tags	396:437	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	0	28	theme	Protein	26:32	arg1	Sites					50:54	Protein O-GlcNAcylation Sites	26:54	Protein O-GlcNAcylation Sites	26:54	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker.
30059200	3	29	from	sites	535:539	arg1	cells					549:553	HeLa cells	544:553	HeLa cells	544:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	2	30	theme	isoTCL	326:331	arg1	strategy					334:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	an isotope-tagged cleavable linker (isoTCL) strategy	290:341	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	6	31	theme	modification	1130:1141	arg1	profiling					1108:1116	quantitative profiling	1095:1116	quantitative profiling of O-GlcNAc modification	1095:1141	The isoTCL platform provides a powerful tool for quantitative profiling of O-GlcNAc modification.
30059200	5	32	theme	sites	880:884	arg1	levels					843:848	the O-GlcNAcylation stoichiometry levels	809:848	the O-GlcNAcylation stoichiometry levels of more than 100 modification sites	809:884	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	1	33	theme	protein	125:131	arg1	N-acetylglucosamine					145:163	protein O-linked β- N-acetylglucosamine	125:163	protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification	125:187	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	33	theme	protein	125:131	arg1	O-GlcNAc					166:173	O-GlcNAc	166:173	O-GlcNAc	166:173	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	34	theme	key	225:227	arg1	challenge					229:237	a key challenge	223:237	a key challenge	223:237	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	0	35	theme	Sites	50:54	arg1	Profiling					13:21	Quantitative Profiling	0:21	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker	0:92	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker.
30059200	3	36	theme	sites	535:539	arg1	quantification					501:514	quantification	501:514	quantification	501:514	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	3	36	theme	sites	535:539	arg1	mapping					489:495	mapping	489:495	mapping	489:495	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	4	37	theme	O-GlcNAc	716:723	arg1	probe					734:738	the O-GlcNAc labeling probe	712:738	the O-GlcNAc labeling probe	712:738	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	3	38	theme	isoTCL	479:484	arg1	application					460:470	the application	456:470	the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells	456:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	0	39	theme	O-GlcNAcylation	34:48	arg1	Sites					50:54	Protein O-GlcNAcylation Sites	26:54	Protein O-GlcNAcylation Sites	26:54	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker.
30059200	5	40	theme	modification	867:878	arg1	sites					880:884	more than 100 modification sites	853:884	more than 100 modification sites	853:884	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	3	41	from	isoTCL	479:484	arg1	quantification					501:514	quantification	501:514	quantification	501:514	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	3	41	from	isoTCL	479:484	arg1	mapping					489:495	mapping	489:495	mapping	489:495	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	2	42	theme	tags	434:437	arg1	conjugation					410:420	bioorthogonal conjugation	396:420	bioorthogonal conjugation of affinity tags	396:437	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	5	43	from	mice	932:935	arg1	samples					903:909	placenta samples	894:909	placenta samples from male and female mice	894:935	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	5	44	contain	has	990:992	arg1	placenta					981:988	female placenta	974:988	female placenta	974:988	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	5	44	contain	has	990:992	arg2	O-GlcNAcylation					1003:1017	a higher O-GlcNAcylation	994:1017	a higher O-GlcNAcylation than its male counterpart	994:1043	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	1	45	theme	O-linked	133:140	arg1	N-acetylglucosamine					145:163	protein O-linked β- N-acetylglucosamine	125:163	protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification	125:187	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	45	theme	O-linked	133:140	arg1	O-GlcNAc					166:173	O-GlcNAc	166:173	O-GlcNAc	166:173	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	3	46	from	mapping	489:495	arg1	cells					549:553	HeLa cells	544:553	HeLa cells	544:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	3	46	from	mapping	489:495	arg1	application					460:470	the application	456:470	the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells	456:553	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	1	47	theme	β-	142:143	arg1	N-acetylglucosamine					145:163	protein O-linked β- N-acetylglucosamine	125:163	protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification	125:187	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	47	theme	β-	142:143	arg1	O-GlcNAc					166:173	O-GlcNAc	166:173	O-GlcNAc	166:173	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	48	link	O-linked	133:140	arg1	N-acetylglucosamine					145:163	protein O-linked β- N-acetylglucosamine	125:163	protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification	125:187	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	48	link	O-linked	133:140	arg1	O-GlcNAc					166:173	O-GlcNAc	166:173	O-GlcNAc	166:173	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	1	49	theme	N-acetylglucosamine	145:163	arg1	modification					176:187	protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification	125:187	protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification	125:187	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	6	50	theme	quantitative	1095:1106	arg1	profiling					1108:1116	quantitative profiling	1095:1116	quantitative profiling of O-GlcNAc modification	1095:1141	The isoTCL platform provides a powerful tool for quantitative profiling of O-GlcNAc modification.
30059200	5	51	theme	female	974:979	arg1	placenta					981:988	female placenta	974:988	female placenta	974:988	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	5	52	theme	male	1028:1031	arg1	counterpart					1033:1043	its male counterpart	1024:1043	its male counterpart	1024:1043	In addition, we applied isoTCL to compare the O-GlcNAcylation stoichiometry levels of more than 100 modification sites between placenta samples from male and female mice and confirmed site-specifically that female placenta has a higher O-GlcNAcylation than its male counterpart.
30059200	4	53	theme	probe	734:738	arg1	concentrations					694:707	different concentrations	684:707	different concentrations of the O-GlcNAc labeling probe	684:738	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	1	54	theme	O-GlcNAc	251:258	arg1	biology					260:266	O-GlcNAc biology	251:266	O-GlcNAc biology	251:266	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	0	55	theme	Cleavable	77:85	arg1	Linker					87:92	an Isotope-Tagged Cleavable Linker	59:92	an Isotope-Tagged Cleavable Linker	59:92	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker.
30059200	4	56	theme	different	684:692	arg1	concentrations					694:707	different concentrations	684:707	different concentrations of the O-GlcNAc labeling probe	684:738	Furthermore, we investigated the O-GlcNAcylation sensitivity to the sugar donor by quantifying the levels of modification under different concentrations of the O-GlcNAc labeling probe in a site-specific manner.
30059200	3	57	from	application	460:470	arg1	quantification					501:514	quantification	501:514	quantification	501:514	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	3	57	from	application	460:470	arg1	mapping					489:495	mapping	489:495	mapping	489:495	We demonstrated the application of the isoTCL in mapping and quantification of O-GlcNAcylation sites in HeLa cells.
30059200	1	58	from	quantification	107:120	arg1	manner					208:213	a site-specific manner	192:213	a site-specific manner	192:213	Large-scale quantification of protein O-linked β- N-acetylglucosamine (O-GlcNAc) modification in a site-specific manner remains a key challenge in studying O-GlcNAc biology.
30059200	0	59	theme	Isotope-Tagged	62:75	arg1	Linker					87:92	an Isotope-Tagged Cleavable Linker	59:92	an Isotope-Tagged Cleavable Linker	59:92	Quantitative Profiling of Protein O-GlcNAcylation Sites by an Isotope-Tagged Cleavable Linker.
30059200	2	60	theme	O-GlcNAc	379:386	arg1	labeling					367:374	isotopic labeling	358:374	isotopic labeling of O-GlcNAc	358:386	Herein, we developed an isotope-tagged cleavable linker (isoTCL) strategy, which enabled isotopic labeling of O-GlcNAc through bioorthogonal conjugation of affinity tags.
30059200	6	61	theme	powerful	1077:1084	arg1	tool					1086:1089	a powerful tool	1075:1089	a powerful tool for quantitative profiling of O-GlcNAc modification	1075:1141	The isoTCL platform provides a powerful tool for quantitative profiling of O-GlcNAc modification.
30158294	12	0	theme	cells	2062:2066	arg1	infection					2042:2050	infection	2042:2050	infection of target cells	2042:2066	These proteins are incorporated into virions and inhibit infection of target cells unless counteracted by viral antagonists such as HIV-1 Nef.
30158294	5	1	mod	modified	751:758	arg3	glycans					776:782	high-mannose glycans	763:782	high-mannose glycans	763:782	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	5	1	mod	modified	751:758	arg1	majority					677:684	the majority	673:684	the majority of SERINC5 in cells	673:704	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	10	2	theme	lysosomal	1520:1528	arg1	A1					1514:1515	bafilomycin A1	1502:1515	bafilomycin A1 (a lysosomal inhibitor)	1502:1539	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	10	2	theme	lysosomal	1520:1528	arg1	inhibitor					1530:1538	a lysosomal inhibitor	1518:1538	a lysosomal inhibitor	1518:1538	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	6	3	theme	family	814:819	arg1	proteins					821:828	SERINC family proteins	807:828	SERINC family proteins	807:828	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	5	4	link	N-linked	638:645	arg1	glycans					656:662	N-linked, complex glycans	638:662	N-linked, complex glycans	638:662	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	9	5	theme	restrictive	1186:1196	arg1	activity					1198:1205	restrictive activity	1186:1205	restrictive activity	1186:1205	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	12	6	theme	target	2055:2060	arg1	cells					2062:2066	target cells	2055:2066	target cells	2055:2066	These proteins are incorporated into virions and inhibit infection of target cells unless counteracted by viral antagonists such as HIV-1 Nef.
30158294	13	7	theme	lipids	2257:2262	arg1	formation					2217:2225	the formation	2213:2225	the formation of serine-containing membrane lipids	2213:2262	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	13	7	theme	lipids	2257:2262	arg1	function					2154:2161	The only other biological function	2128:2161	The only other biological function with which these proteins have been associated	2128:2208	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	7	8	from	activity	979:986	arg1	glycosylation					948:960	glycosylation	948:960	glycosylation	948:960	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	6	9	theme	Sequence	785:792	arg1	alignment					794:802	Sequence alignment	785:802	Sequence alignment of SERINC family proteins	785:828	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	1	10	theme	HIV-1	183:187	arg1	Nef					189:191	HIV-1 Nef	183:191	HIV-1 Nef	183:191	SERINC5 is an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef.
30158294	6	11	from	site	877:880	arg1	SERINC5					892:898	SERINC5	892:898	SERINC5	892:898	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	5	12	theme	various	558:564	arg1	glycosidases					566:577	various glycosidases	558:577	various glycosidases	558:577	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	13	13	theme	other	2137:2141	arg1	formation					2217:2225	the formation	2213:2225	the formation of serine-containing membrane lipids	2213:2262	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	13	13	theme	other	2137:2141	arg1	function					2154:2161	The only other biological function	2128:2161	The only other biological function with which these proteins have been associated	2128:2208	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	11	14	theme	proteasomal	1819:1829	arg1	SERINC5					1854:1860	its proteasomal degradation.IMPORTANCE SERINC5	1815:1860	its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1815:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	5	15	theme	low	723:725	arg1	weight					737:742	relatively low molecular weight	712:742	relatively low molecular weight	712:742	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	15	16	from	prone	2434:2438	arg1	absence					2395:2401	the absence	2391:2401	the absence of N-glycosylation	2391:2420	In the absence of N-glycosylation, SERINC5 is prone to proteasomal degradation.
30158294	5	17	theme	SERINC5	689:695	arg1	majority					677:684	the majority	673:684	the majority of SERINC5 in cells	673:704	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	2	18	theme	infectivity	208:218	arg1	Inhibition					194:203	Inhibition	194:203	Inhibition of infectivity by SERINC5	194:229	Inhibition of infectivity by SERINC5 is associated with its incorporation into virions.
30158294	7	19	theme	SERINC5	991:997	arg1	activity					979:986	the restrictive activity	963:986	the restrictive activity of SERINC5	963:997	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	7	19	theme	SERINC5	991:997	arg1	sensitivity					1008:1018	the sensitivity	1004:1018	the sensitivity of SERINC5 to antagonism by Nef	1004:1050	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	7	19	theme	SERINC5	991:997	arg1	effect					938:943	its effect	934:943	its effect on glycosylation	934:960	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	1	20	theme	retroviral	110:119	arg1	infectivity					121:131	retroviral infectivity	110:131	retroviral infectivity	110:131	SERINC5 is an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef.
30158294	14	21	gly	glycosylated	2296:2307	arg1	SERINC5					2283:2289	SERINC5	2283:2289	SERINC5	2283:2289	Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady state expression.
30158294	14	21	gly	glycosylated	2296:2307	arg1	protein					2309:2315	a glycosylated protein	2294:2315	a glycosylated protein	2294:2315	Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady state expression.
30158294	6	22	theme	proteins	821:828	arg1	alignment					794:802	Sequence alignment	785:802	Sequence alignment of SERINC family proteins	785:828	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	12	23	theme	HIV-1	2117:2121	arg1	Nef					2123:2125	HIV-1 Nef	2117:2125	HIV-1 Nef	2117:2125	These proteins are incorporated into virions and inhibit infection of target cells unless counteracted by viral antagonists such as HIV-1 Nef.
30158294	14	24	theme	steady	2363:2368	arg1	expression					2376:2385	its steady state expression	2359:2385	its steady state expression	2359:2385	Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady state expression.
30158294	11	25	theme	non-glycosylated	1726:1741	arg1	SERINC5					1743:1749	non-glycosylated SERINC5	1726:1749	non-glycosylated SERINC5	1726:1749	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	7	26	from	effect	938:943	arg1	glycosylation					948:960	glycosylation	948:960	glycosylation	948:960	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	3	27	from	membrane	390:397	arg1	sites					351:355	sites	351:355	sites of virion assembly at the plasma membrane	351:397	Nef counteracts this inhibition, presumably by removing SERINC5 from sites of virion assembly at the plasma membrane.
30158294	3	27	from	membrane	390:397	arg1	assembly					367:374	virion assembly	360:374	virion assembly	360:374	Nef counteracts this inhibition, presumably by removing SERINC5 from sites of virion assembly at the plasma membrane.
30158294	14	28	gly	N-glycosylation	2326:2340	arg1	state					2370:2374	its steady state expression	2359:2385	its steady state expression	2359:2385	Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady state expression.
30158294	4	29	theme	weight	499:504	arg1	form					506:509	a relatively high molecular weight form	471:509	a relatively high molecular weight form	471:509	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	12	30	theme	viral	2091:2095	arg1	Nef					2123:2125	HIV-1 Nef	2117:2125	HIV-1 Nef	2117:2125	These proteins are incorporated into virions and inhibit infection of target cells unless counteracted by viral antagonists such as HIV-1 Nef.
30158294	12	30	theme	viral	2091:2095	arg1	antagonists					2097:2107	viral antagonists	2091:2107	viral antagonists such as HIV-1 Nef	2091:2125	These proteins are incorporated into virions and inhibit infection of target cells unless counteracted by viral antagonists such as HIV-1 Nef.
30158294	15	31	theme	proteasomal	2443:2453	arg1	degradation					2455:2465	proteasomal degradation	2443:2465	proteasomal degradation	2443:2465	In the absence of N-glycosylation, SERINC5 is prone to proteasomal degradation.
30158294	1	32	theme	viral	157:161	arg1	proteins					163:170	viral proteins	157:170	viral proteins	157:170	SERINC5 is an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef.
30158294	1	32	theme	viral	157:161	arg1	Nef					189:191	HIV-1 Nef	183:191	HIV-1 Nef	183:191	SERINC5 is an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef.
30158294	5	33	used	used	553:556	arg2	We					550:551	We	550:551	We	550:551	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	15	34	from	absence	2395:2401	arg1	prone					2434:2438	prone	2434:2438	prone	2434:2438	In the absence of N-glycosylation, SERINC5 is prone to proteasomal degradation.
30158294	10	35	theme	mutant	1404:1409	arg1	Expression					1385:1394	Expression	1385:1394	Expression of this mutant	1385:1409	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	9	36	theme	steady	1272:1277	arg1	state					1279:1283	the steady state	1268:1283	the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant)	1268:1348	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	16	37	gly	N-glycosylation	2481:2495	arg1	SERINC5					2543:2549	SERINC5	2543:2549	SERINC5	2543:2549	Nonetheless, N-glycosylation per se is neither required for the ability of SERINC5 to inhibit HIV-1 infectivity nor for its sensitivity to antagonism by Nef.
30158294	11	38	theme	proteins	1914:1921	arg1	family					1879:1884	a family	1877:1884	a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1877:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	4	39	theme	high	484:487	arg1	weight					499:504	a relatively high molecular weight	471:504	a relatively high molecular weight form	471:509	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	4	40	located	present	530:536	arg1	virions					541:547	virions	541:547	virions	541:547	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	4	40	located	present	530:536	arg2	form					506:509	a relatively high molecular weight form	471:509	a relatively high molecular weight form	471:509	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	11	41	theme	multi-pass	1889:1898	arg1	proteins					1914:1921	multi-pass transmembrane proteins	1889:1921	multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1889:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	9	42	theme	glycosylation-deficient	1299:1321	arg1	mutant					1342:1347	the N294A mutant	1332:1347	the N294A mutant	1332:1347	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	9	42	theme	glycosylation-deficient	1299:1321	arg1	SERINC5					1323:1329	glycosylation-deficient SERINC5	1299:1329	glycosylation-deficient SERINC5 (the N294A mutant)	1299:1348	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	3	43	theme	assembly	367:374	arg1	sites					351:355	sites	351:355	sites of virion assembly at the plasma membrane	351:397	Nef counteracts this inhibition, presumably by removing SERINC5 from sites of virion assembly at the plasma membrane.
30158294	3	43	theme	assembly	367:374	arg1	assembly					367:374	virion assembly	360:374	virion assembly	360:374	Nef counteracts this inhibition, presumably by removing SERINC5 from sites of virion assembly at the plasma membrane.
30158294	11	44	link	N-linked	1626:1633	arg1	glycosylation					1635:1647	N-linked glycosylation	1626:1647	N-linked glycosylation	1626:1647	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	6	45	gly	N-glycosylation	861:875	arg2	N294					883:886	N294	883:886	N294	883:886	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	6	45	gly	N-glycosylation	861:875	arg2	site					877:880	a conserved N-glycosylation site	849:880	a conserved N-glycosylation site	849:880	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	4	46	from	virions	541:547	arg1	present					530:536	present	530:536	present	530:536	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	9	47	theme	N294A	1336:1340	arg1	mutant					1342:1347	the N294A mutant	1332:1347	the N294A mutant	1332:1347	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	9	47	theme	N294A	1336:1340	arg1	SERINC5					1323:1329	glycosylation-deficient SERINC5	1299:1329	glycosylation-deficient SERINC5 (the N294A mutant)	1299:1348	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	0	48	theme	SERINC5	26:32	arg1	form					18:21	An N-glycosylated form	0:21	An N-glycosylated form of SERINC5	0:32	An N-glycosylated form of SERINC5 is specifically incorporated into HIV-1 virions.
30158294	6	49	theme	N-glycosylation	861:875	arg1	N294					883:886	N294	883:886	N294	883:886	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	6	49	theme	N-glycosylation	861:875	arg1	site					877:880	a conserved N-glycosylation site	849:880	a conserved N-glycosylation site	849:880	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	0	50	gly	N-glycosylated	3:16	arg1	form					18:21	An N-glycosylated form	0:21	An N-glycosylated form of SERINC5	0:32	An N-glycosylated form of SERINC5 is specifically incorporated into HIV-1 virions.
30158294	0	50	gly	N-glycosylated	3:16	arg1	SERINC5					26:32	SERINC5	26:32	SERINC5	26:32	An N-glycosylated form of SERINC5 is specifically incorporated into HIV-1 virions.
30158294	5	51	dep	N-linked	638:645	arg1	complex					648:654	complex	648:654	complex	648:654	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	4	52	from	present	530:536	arg1	virions					541:547	virions	541:547	virions	541:547	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	13	53	theme	serine-containing	2230:2246	arg1	lipids					2257:2262	serine-containing membrane lipids	2230:2262	serine-containing membrane lipids	2230:2262	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	16	54	theme	SERINC5	2543:2549	arg1	ability					2532:2538	the ability	2528:2538	the ability of SERINC5 to inhibit HIV-1 infectivity	2528:2578	Nonetheless, N-glycosylation per se is neither required for the ability of SERINC5 to inhibit HIV-1 infectivity nor for its sensitivity to antagonism by Nef.
30158294	5	55	dep	modified	626:633	arg1	whereas					665:671	whereas	665:671	whereas	665:671	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	11	56	theme	SERINC5	1709:1715	arg1	expression					1695:1704	the steady-state expression	1678:1704	the steady-state expression of SERINC5	1678:1715	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	11	57	theme	family	1879:1884	arg1	member					1867:1872	a member	1865:1872	a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1865:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	9	58	theme	wild	1366:1369	arg1	protein					1376:1382	the wild type protein	1362:1382	the wild type protein	1362:1382	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	8	59	theme	N-glycosylation	1108:1122	arg1	N-glycosylation					1108:1122	N-glycosylation	1108:1122	N-glycosylation	1108:1122	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	59	theme	N-glycosylation	1108:1122	arg1	site					1100:1103	the major site	1090:1103	the major site of N-glycosylation in SERINC5	1090:1133	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	59	theme	N-glycosylation	1108:1122	arg1	N294					1082:1085	N294	1082:1085	N294	1082:1085	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	6	60	theme	conserved	851:859	arg1	N294					883:886	N294	883:886	N294	883:886	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	6	60	theme	conserved	851:859	arg1	site					877:880	a conserved N-glycosylation site	849:880	a conserved N-glycosylation site	849:880	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	5	61	mod	modified	626:633	arg3	glycans					656:662	N-linked, complex glycans	638:662	N-linked, complex glycans	638:662	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	5	61	mod	modified	626:633	arg1	SERINC5					615:621	virion-associated SERINC5	597:621	virion-associated SERINC5	597:621	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	5	62	theme	N-linked	638:645	arg1	glycans					656:662	N-linked, complex glycans	638:662	N-linked, complex glycans	638:662	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	6	63	theme	SERINC	807:812	arg1	proteins					821:828	SERINC family proteins	807:828	SERINC family proteins	807:828	Sequence alignment of SERINC family proteins led us to identify a conserved N-glycosylation site, N294, in SERINC5.
30158294	11	64	theme	N-linked	1626:1633	arg1	glycosylation					1635:1647	N-linked glycosylation	1626:1647	N-linked glycosylation	1626:1647	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	4	65	attach	present	530:536	arg1	virions					541:547	virions	541:547	virions	541:547	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	4	65	attach	present	530:536	arg2	form					506:509	a relatively high molecular weight form	471:509	a relatively high molecular weight form	471:509	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	11	66	theme	quality-control	1776:1790	arg1	mechanism					1792:1800	a quality-control mechanism	1774:1800	a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1774:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	13	67	theme	biological	2143:2152	arg1	formation					2217:2225	the formation	2213:2225	the formation of serine-containing membrane lipids	2213:2262	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	13	67	theme	biological	2143:2152	arg1	function					2154:2161	The only other biological function	2128:2161	The only other biological function with which these proteins have been associated	2128:2208	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	11	68	theme	degradation.IMPORTANCE	1831:1852	arg1	SERINC5					1854:1860	its proteasomal degradation.IMPORTANCE SERINC5	1815:1860	its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1815:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	7	69	theme	SERINC5	1023:1029	arg1	activity					979:986	the restrictive activity	963:986	the restrictive activity of SERINC5	963:997	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	7	69	theme	SERINC5	1023:1029	arg1	sensitivity					1008:1018	the sensitivity	1004:1018	the sensitivity of SERINC5 to antagonism by Nef	1004:1050	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	7	69	theme	SERINC5	1023:1029	arg1	effect					938:943	its effect	934:943	its effect on glycosylation	934:960	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	11	70	theme	retroviruses	1955:1966	arg1	infectivity					1940:1950	the infectivity	1936:1950	the infectivity of retroviruses including HIV-1	1936:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	9	71	from	decrease	1256:1263	arg1	expression					1285:1294	the steady state expression	1268:1294	the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant)	1268:1348	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	14	72	theme	state	2370:2374	arg1	expression					2376:2385	its steady state expression	2359:2385	its steady state expression	2359:2385	Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady state expression.
30158294	1	73	theme	infectivity	121:131	arg1	SERINC5					83:89	SERINC5	83:89	SERINC5	83:89	SERINC5 is an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef.
30158294	1	73	theme	infectivity	121:131	arg1	inhibitor					97:105	an inhibitor	94:105	an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef	94:191	SERINC5 is an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef.
30158294	10	74	with	cells	1447:1451	arg1	MG132					1458:1462	MG132	1458:1462	MG132 (a proteasome-inhibitor)	1458:1487	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	10	74	with	cells	1447:1451	arg1	proteasome-inhibitor					1467:1486	a proteasome-inhibitor	1465:1486	a proteasome-inhibitor	1465:1486	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	10	74	with	cells	1447:1451	arg1	A1					1514:1515	bafilomycin A1	1502:1515	bafilomycin A1 (a lysosomal inhibitor)	1502:1539	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	10	74	with	cells	1447:1451	arg1	inhibitor					1530:1538	a lysosomal inhibitor	1518:1538	a lysosomal inhibitor	1518:1538	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	4	75	theme	SERINC5	445:451	arg1	virion-incorporation					421:440	the virion-incorporation	417:440	the virion-incorporation of SERINC5	417:451	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	0	76	theme	HIV-1	68:72	arg1	virions					74:80	HIV-1 virions	68:80	HIV-1 virions	68:80	An N-glycosylated form of SERINC5 is specifically incorporated into HIV-1 virions.
30158294	5	77	theme	high-mannose	763:774	arg1	glycans					776:782	high-mannose glycans	763:782	high-mannose glycans	763:782	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	7	78	theme	restrictive	967:977	arg1	activity					979:986	the restrictive activity	963:986	the restrictive activity of SERINC5	963:997	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	15	79	theme	N-glycosylation	2406:2420	arg1	absence					2395:2401	the absence	2391:2401	the absence of N-glycosylation	2391:2420	In the absence of N-glycosylation, SERINC5 is prone to proteasomal degradation.
30158294	5	80	theme	molecular	727:735	arg1	weight					737:742	relatively low molecular weight	712:742	relatively low molecular weight	712:742	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	11	81	dep	SERINC5	1854:1860	arg1	member					1867:1872	a member	1865:1872	a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1865:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	3	82	theme	virion	360:365	arg1	assembly					367:374	virion assembly	360:374	virion assembly	360:374	Nef counteracts this inhibition, presumably by removing SERINC5 from sites of virion assembly at the plasma membrane.
30158294	9	83	theme	state	1279:1283	arg1	expression					1285:1294	the steady state expression	1268:1294	the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant)	1268:1348	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	4	84	theme	molecular	489:497	arg1	weight					499:504	a relatively high molecular weight	471:504	a relatively high molecular weight form	471:509	While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions.
30158294	14	85	theme	glycosylated	2296:2307	arg1	SERINC5					2283:2289	SERINC5	2283:2289	SERINC5	2283:2289	Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady state expression.
30158294	14	85	theme	glycosylated	2296:2307	arg1	protein					2309:2315	a glycosylated protein	2294:2315	a glycosylated protein	2294:2315	Here we show that SERINC5 is a glycosylated protein and that N-glycosylation is important for its steady state expression.
30158294	0	86	theme	N-glycosylated	3:16	arg1	form					18:21	An N-glycosylated form	0:21	An N-glycosylated form of SERINC5	0:32	An N-glycosylated form of SERINC5 is specifically incorporated into HIV-1 virions.
30158294	3	87	theme	plasma	383:388	arg1	membrane					390:397	the plasma membrane	379:397	the plasma membrane	379:397	Nef counteracts this inhibition, presumably by removing SERINC5 from sites of virion assembly at the plasma membrane.
30158294	11	88	gly	non-glycosylated	1726:1741	arg1	SERINC5					1743:1749	non-glycosylated SERINC5	1726:1749	non-glycosylated SERINC5	1726:1749	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	11	89	theme	transmembrane	1900:1912	arg1	proteins					1914:1921	multi-pass transmembrane proteins	1889:1921	multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1	1889:1982	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	9	90	theme	SERINC5	1323:1329	arg1	expression					1285:1294	the steady state expression	1268:1294	the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant)	1268:1348	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	5	91	theme	virion-associated	597:613	arg1	SERINC5					615:621	virion-associated SERINC5	597:621	virion-associated SERINC5	597:621	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	10	92	theme	cells	1447:1451	arg1	treatment					1434:1442	treatment	1434:1442	treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor)	1434:1539	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	5	93	from	majority	677:684	arg1	cells					700:704	cells	700:704	cells	700:704	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	8	94	from	site	1100:1103	arg1	SERINC5					1127:1133	SERINC5	1127:1133	SERINC5	1127:1133	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	95	gly	N-glycosylation	1108:1122	arg2	site					1100:1103	the major site	1090:1103	the major site of N-glycosylation in SERINC5	1090:1133	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	95	gly	N-glycosylation	1108:1122	arg2	N294					1082:1085	N294	1082:1085	N294	1082:1085	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	95	gly	N-glycosylation	1108:1122	arg1	SERINC5					1127:1133	SERINC5	1127:1133	SERINC5	1127:1133	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	95	gly	N-glycosylation	1108:1122	arg2	N-glycosylation					1108:1122	N-glycosylation	1108:1122	N-glycosylation	1108:1122	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	13	96	theme	membrane	2248:2255	arg1	lipids					2257:2262	serine-containing membrane lipids	2230:2262	serine-containing membrane lipids	2230:2262	The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids.
30158294	8	97	theme	major	1094:1098	arg1	N-glycosylation					1108:1122	N-glycosylation	1108:1122	N-glycosylation	1108:1122	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	97	theme	major	1094:1098	arg1	site					1100:1103	the major site	1090:1103	the major site of N-glycosylation in SERINC5	1090:1133	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	8	97	theme	major	1094:1098	arg1	N294					1082:1085	N294	1082:1085	N294	1082:1085	Our results demonstrate that N294 is the major site of N-glycosylation in SERINC5.
30158294	7	98	from	sensitivity	1008:1018	arg1	glycosylation					948:960	glycosylation	948:960	glycosylation	948:960	We mutated this site to evaluate its effect on glycosylation, the restrictive activity of SERINC5, and the sensitivity of SERINC5 to antagonism by Nef.
30158294	11	99	theme	steady-state	1682:1693	arg1	expression					1695:1704	the steady-state expression	1678:1704	the steady-state expression of SERINC5	1678:1715	We conclude that although not required for restrictive-activity or Nef-sensitivity, N-linked glycosylation is important for maintaining the steady-state expression of SERINC5 and that non-glycosylated SERINC5 is likely subjected to a quality-control mechanism that induces its proteasomal degradation.IMPORTANCE SERINC5 is a member of a family of multi-pass transmembrane proteins that inhibit the infectivity of retroviruses including HIV-1.
30158294	5	100	from	cells	700:704	arg1	majority					677:684	the majority	673:684	the majority of SERINC5 in cells	673:704	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
30158294	16	101	theme	HIV-1	2562:2566	arg1	infectivity					2568:2578	HIV-1 infectivity	2562:2578	HIV-1 infectivity	2562:2578	Nonetheless, N-glycosylation per se is neither required for the ability of SERINC5 to inhibit HIV-1 infectivity nor for its sensitivity to antagonism by Nef.
30158294	10	102	theme	bafilomycin	1502:1512	arg1	A1					1514:1515	bafilomycin A1	1502:1515	bafilomycin A1 (a lysosomal inhibitor)	1502:1539	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	10	102	theme	bafilomycin	1502:1512	arg1	inhibitor					1530:1538	a lysosomal inhibitor	1518:1538	a lysosomal inhibitor	1518:1538	Expression of this mutant was partly restored by treatment of cells with MG132 (a proteasome-inhibitor) but not with bafilomycin A1 (a lysosomal inhibitor).
30158294	9	103	theme	type	1371:1374	arg1	protein					1376:1382	the wild type protein	1362:1382	the wild type protein	1362:1382	Although N-glycosylation was neither required for restrictive activity nor for sensitivity to Nef per se, we observed a decrease in the steady state expression of glycosylation-deficient SERINC5 (the N294A mutant) compared to the wild type protein.
30158294	5	104	from	SERINC5	689:695	arg1	cells					700:704	cells	700:704	cells	700:704	We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans.
29304374	0	0	theme	Defective	78:86	arg1	Fucosylation					88:99	Defective Fucosylation	78:99	Defective Fucosylation	78:99	Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.
29304374	6	1	theme	Splicing	928:935	arg1	analysis					937:944	Splicing analysis	928:944	Splicing analysis	928:944	Splicing analysis confirmed the c.1259+5G>T resulted in expression of an abnormal FUT8 transcript lacking exon 9.
29304374	7	2	theme	protein	1150:1156	arg1	expression					1158:1167	FUT8 protein expression	1145:1167	FUT8 protein expression	1145:1167	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	9	3	theme	congenital	1420:1429	arg1	disorder					1431:1438	a congenital disorder	1418:1438	a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse	1418:1584	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	1	4	theme	α1,6	156:159	arg1	essential					188:196	essential	188:196	essential	188:196	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	1	4	theme	α1,6	156:159	arg1	process					272:278	a process	270:278	a process known as "core fucosylation	270:306	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	1	4	theme	α1,6	156:159	arg1	Fucosyltransferase					102:119	Fucosyltransferase 8	102:121	Fucosyltransferase 8 (FUT8)	102:128	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	1	4	theme	α1,6	156:159	arg1	fucosyltransferase					161:178	a Golgi-localized α1,6 fucosyltransferase	138:178	a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins	138:267	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	7	5	theme	primary	1067:1073	arg1	fibroblasts					1075:1085	primary fibroblasts	1067:1085	primary fibroblasts from two affected individuals	1067:1115	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	9	6	theme	glycosylation	1443:1455	arg1	disorder					1431:1438	a congenital disorder	1418:1438	a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse	1418:1584	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	2	7	theme	respiratory	499:509	arg1	complications					511:523	respiratory complications	499:523	respiratory complications	499:523	Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications.
29304374	0	8	from	Mutations	10:18	arg1	FUT8					23:26	FUT8	23:26	FUT8	23:26	Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.
29304374	7	9	theme	expression	1158:1167	arg1	lack					1137:1140	a complete lack	1126:1140	a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans	1126:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	8	10	theme	serum	1272:1276	arg1	samples					1278:1284	serum samples	1272:1284	serum samples from all three individuals	1272:1311	Furthermore, serum samples from all three individuals showed a complete loss of core fucosylation.
29304374	3	11	theme	whole-exome	541:551	arg1	sequencing					553:562	whole-exome sequencing	541:562	whole-exome sequencing	541:562	Each underwent whole-exome sequencing and was found to carry pathogenic variants in FUT8.
29304374	10	12	theme	additional	1618:1627	arg1	individuals					1638:1648	additional affected individuals	1618:1648	additional affected individuals	1618:1648	Importantly, identification of additional affected individuals can be easily achieved through analysis of core fucosylation of N-glycans.
29304374	6	13	theme	transcript	1015:1024	arg1	expression					984:993	expression	984:993	expression of an abnormal FUT8 transcript lacking exon 9	984:1039	Splicing analysis confirmed the c.1259+5G>T resulted in expression of an abnormal FUT8 transcript lacking exon 9.
29304374	9	14	theme	knockout	1571:1578	arg1	mouse					1580:1584	the Fut8-/- knockout mouse	1559:1584	the Fut8-/- knockout mouse	1559:1584	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	9	15	from	mutations	1394:1402	arg1	FUT8					1407:1410	FUT8	1407:1410	FUT8	1407:1410	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	10	16	gly	fucosylation	1698:1709	arg1	N-glycans					1714:1722	N-glycans	1714:1722	N-glycans	1714:1722	Importantly, identification of additional affected individuals can be easily achieved through analysis of core fucosylation of N-glycans.
29304374	6	17	theme	FUT8	1010:1013	arg1	transcript					1015:1024	an abnormal FUT8 transcript	998:1024	an abnormal FUT8 transcript lacking exon 9	998:1039	Splicing analysis confirmed the c.1259+5G>T resulted in expression of an abnormal FUT8 transcript lacking exon 9.
29304374	10	18	theme	individuals	1638:1648	arg1	identification					1600:1613	identification	1600:1613	identification of additional affected individuals	1600:1648	Importantly, identification of additional affected individuals can be easily achieved through analysis of core fucosylation of N-glycans.
29304374	6	19	theme	abnormal	1001:1008	arg1	transcript					1015:1024	an abnormal FUT8 transcript	998:1024	an abnormal FUT8 transcript lacking exon 9	998:1039	Splicing analysis confirmed the c.1259+5G>T resulted in expression of an abnormal FUT8 transcript lacking exon 9.
29304374	1	20	dep	encodes	130:136	arg1	"					308:308	"	308:308	"	308:308	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	4	21	theme	first	620:624	arg1	individual					626:635	The first individual	616:635	The first individual (consanguineous family)	616:659	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	4	21	theme	first	620:624	arg1	family					653:658	consanguineous family	638:658	consanguineous family	638:658	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	4	21	theme	first	620:624	arg1	homozygous					665:674	homozygous	665:674	homozygous	665:674	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	7	22	theme	core	1231:1234	arg1	N-glycans					1248:1256	total core fucosylated N-glycans	1225:1256	total core fucosylated N-glycans	1225:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	7	23	from	deficiencies	1209:1220	arg1	N-glycans					1248:1256	total core fucosylated N-glycans	1225:1256	total core fucosylated N-glycans	1225:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	7	24	theme	complete	1128:1135	arg1	lack					1137:1140	a complete lack	1126:1140	a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans	1126:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	1	25	gly	glycoproteins	255:267	arg1	glycoproteins					255:267	N-linked glycoproteins	246:267	N-linked glycoproteins	246:267	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	7	26	gly	fucosylated	1236:1246	arg1	N-glycans					1248:1256	total core fucosylated N-glycans	1225:1256	total core fucosylated N-glycans	1225:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	10	27	theme	N-glycans	1714:1722	arg1	fucosylation					1698:1709	core fucosylation	1693:1709	core fucosylation of N-glycans	1693:1722	Importantly, identification of additional affected individuals can be easily achieved through analysis of core fucosylation of N-glycans.
29304374	2	28	theme	neurological	469:480	arg1	impairments					482:492	neurological impairments	469:492	neurological impairments	469:492	Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications.
29304374	7	29	theme	total	1225:1229	arg1	N-glycans					1248:1256	total core fucosylated N-glycans	1225:1256	total core fucosylated N-glycans	1225:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	7	30	from	individuals	1105:1115	arg1	fibroblasts					1075:1085	primary fibroblasts	1067:1085	primary fibroblasts from two affected individuals	1067:1115	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	10	31	theme	affected	1629:1636	arg1	individuals					1638:1648	additional affected individuals	1618:1648	additional affected individuals	1618:1648	Importantly, identification of additional affected individuals can be easily achieved through analysis of core fucosylation of N-glycans.
29304374	9	32	theme	mouse	1580:1584	arg1	aspects					1548:1554	some aspects	1543:1554	some aspects of the Fut8-/- knockout mouse	1543:1584	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	9	33	theme	defective	1485:1493	arg1	fucosylation					1500:1511	defective core fucosylation	1485:1511	defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse	1485:1584	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	0	34	theme	Biallelic	0:8	arg1	Mutations					10:18	Biallelic Mutations	0:18	Biallelic Mutations in FUT8	0:26	Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.
29304374	9	35	from	loss	1377:1380	arg1	FUT8					1407:1410	FUT8	1407:1410	FUT8	1407:1410	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	2	36	theme	growth	388:393	arg1	retardation					395:405	intrauterine growth retardation	375:405	intrauterine growth retardation	375:405	Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications.
29304374	2	37	theme	shortened	452:460	arg1	limbs					462:466	shortened limbs	452:466	shortened limbs	452:466	Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications.
29304374	1	38	theme	core	290:293	arg1	fucosylation					295:306	"core fucosylation	289:306	"core fucosylation	289:306	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	7	39	theme	affected	1096:1103	arg1	individuals					1105:1115	two affected individuals	1092:1115	two affected individuals	1092:1115	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	1	40	link	N-linked	246:253	arg1	glycoproteins					255:267	N-linked glycoproteins	246:267	N-linked glycoproteins	246:267	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	3	41	theme	pathogenic	587:596	arg1	variants					598:605	pathogenic variants	587:605	pathogenic variants in FUT8	587:613	Each underwent whole-exome sequencing and was found to carry pathogenic variants in FUT8.
29304374	9	42	from	FUT8	1407:1410	arg1	loss					1377:1380	loss	1377:1380	loss of function mutations in FUT8	1377:1410	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	5	43	theme	third	844:848	arg1	individual					850:859	The third individual	840:859	The third individual (consanguineous family)	840:883	The third individual (consanguineous family) was homozygous for a c.943C>T (p.Arg315∗).
29304374	5	43	theme	third	844:848	arg1	family					877:882	consanguineous family	862:882	consanguineous family	862:882	The third individual (consanguineous family) was homozygous for a c.943C>T (p.Arg315∗).
29304374	5	43	theme	third	844:848	arg1	homozygous					889:898	homozygous	889:898	homozygous	889:898	The third individual (consanguineous family) was homozygous for a c.943C>T (p.Arg315∗).
29304374	2	44	theme	growth	433:438	arg1	delays					440:445	growth delays	433:445	growth delays	433:445	Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications.
29304374	10	45	theme	fucosylation	1698:1709	arg1	analysis					1681:1688	analysis	1681:1688	analysis of core fucosylation of N-glycans	1681:1722	Importantly, identification of additional affected individuals can be easily achieved through analysis of core fucosylation of N-glycans.
29304374	9	46	theme	function	1385:1392	arg1	mutations					1394:1402	function mutations	1385:1402	function mutations in FUT8	1385:1410	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	5	47	theme	consanguineous	862:875	arg1	individual					850:859	The third individual	840:859	The third individual (consanguineous family)	840:883	The third individual (consanguineous family) was homozygous for a c.943C>T (p.Arg315∗).
29304374	5	47	theme	consanguineous	862:875	arg1	family					877:882	consanguineous family	862:882	consanguineous family	862:882	The third individual (consanguineous family) was homozygous for a c.943C>T (p.Arg315∗).
29304374	9	48	theme	core	1495:1498	arg1	fucosylation					1500:1511	defective core fucosylation	1485:1511	defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse	1485:1584	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	1	49	theme	monosaccharide	219:232	arg1	fucose					234:239	the monosaccharide fucose	215:239	the monosaccharide fucose	215:239	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	10	50	theme	core	1693:1696	arg1	fucosylation					1698:1709	core fucosylation	1693:1709	core fucosylation of N-glycans	1693:1722	Importantly, identification of additional affected individuals can be easily achieved through analysis of core fucosylation of N-glycans.
29304374	9	51	theme	mutations	1394:1402	arg1	loss					1377:1380	loss	1377:1380	loss of function mutations in FUT8	1377:1410	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	7	52	theme	substantial	1197:1207	arg1	deficiencies					1209:1220	substantial deficiencies	1197:1220	substantial deficiencies in total core fucosylated N-glycans	1197:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	8	53	from	individuals	1301:1311	arg1	samples					1278:1284	serum samples	1272:1284	serum samples from all three individuals	1272:1311	Furthermore, serum samples from all three individuals showed a complete loss of core fucosylation.
29304374	7	54	theme	fucosylated	1236:1246	arg1	N-glycans					1248:1256	total core fucosylated N-glycans	1225:1256	total core fucosylated N-glycans	1225:1256	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	6	55	dep	confirmed	946:954	arg1	resulted					972:979	resulted	972:979	confirmed the c.1259+5G>T resulted in expression of an abnormal FUT8 transcript lacking exon 9	946:1039	Splicing analysis confirmed the c.1259+5G>T resulted in expression of an abnormal FUT8 transcript lacking exon 9.
29304374	7	56	theme	Functional	1042:1051	arg1	studies					1053:1059	Functional studies	1042:1059	Functional studies using primary fibroblasts from two affected individuals	1042:1115	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29304374	8	57	theme	core	1339:1342	arg1	fucosylation					1344:1355	core fucosylation	1339:1355	core fucosylation	1339:1355	Furthermore, serum samples from all three individuals showed a complete loss of core fucosylation.
29304374	0	58	theme	Congenital	36:45	arg1	Disorder					47:54	a Congenital Disorder	34:54	a Congenital Disorder of Glycosylation with Defective Fucosylation	34:99	Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.
29304374	3	59	contain	carry	581:585	arg2	variants					598:605	pathogenic variants	587:605	pathogenic variants in FUT8	587:613	Each underwent whole-exome sequencing and was found to carry pathogenic variants in FUT8.
29304374	3	59	contain	carry	581:585	arg1	Each					526:529	Each	526:529	Each	526:529	Each underwent whole-exome sequencing and was found to carry pathogenic variants in FUT8.
29304374	4	60	theme	non-consanguineous	720:737	arg1	second					712:717	second	712:717	second	712:717	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	4	60	theme	non-consanguineous	720:737	arg1	family					739:744	non-consanguineous family	720:744	non-consanguineous family	720:744	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	4	61	theme	splice	807:812	arg1	variant					819:825	a splice site variant c.1259+5G>T	805:837	a splice site variant c.1259+5G>T	805:837	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	2	62	theme	unrelated	333:341	arg1	individuals					343:353	three unrelated individuals	327:353	three unrelated individuals	327:353	Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications.
29304374	3	63	from	variants	598:605	arg1	FUT8					610:613	FUT8	610:613	FUT8	610:613	Each underwent whole-exome sequencing and was found to carry pathogenic variants in FUT8.
29304374	4	64	theme	consanguineous	638:651	arg1	individual					626:635	The first individual	616:635	The first individual (consanguineous family)	616:659	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	4	64	theme	consanguineous	638:651	arg1	family					653:658	consanguineous family	638:658	consanguineous family	638:658	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	0	65	with	Disorder	47:54	arg1	Fucosylation					88:99	Defective Fucosylation	78:99	Defective Fucosylation	78:99	Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.
29304374	8	66	theme	fucosylation	1344:1355	arg1	loss					1331:1334	a complete loss	1320:1334	a complete loss of core fucosylation	1320:1355	Furthermore, serum samples from all three individuals showed a complete loss of core fucosylation.
29304374	1	67	theme	N-linked	246:253	arg1	glycoproteins					255:267	N-linked glycoproteins	246:267	N-linked glycoproteins	246:267	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	0	68	theme	Glycosylation	59:71	arg1	Disorder					47:54	a Congenital Disorder	34:54	a Congenital Disorder of Glycosylation with Defective Fucosylation	34:99	Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.
29304374	8	69	theme	complete	1322:1329	arg1	loss					1331:1334	a complete loss	1320:1334	a complete loss of core fucosylation	1320:1355	Furthermore, serum samples from all three individuals showed a complete loss of core fucosylation.
29304374	9	70	theme	Fut8-/-	1563:1569	arg1	mouse					1580:1584	the Fut8-/- knockout mouse	1559:1584	the Fut8-/- knockout mouse	1559:1584	Here, we show that loss of function mutations in FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by defective core fucosylation that phenotypically parallels some aspects of the Fut8-/- knockout mouse.
29304374	2	71	theme	intrauterine	375:386	arg1	retardation					395:405	intrauterine growth retardation	375:405	intrauterine growth retardation	375:405	Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications.
29304374	4	72	theme	site	814:817	arg1	variant					819:825	a splice site variant c.1259+5G>T	805:837	a splice site variant c.1259+5G>T	805:837	The first individual (consanguineous family) was homozygous for c.715C>T (p.Arg239∗), while the second (non-consanguineous family) was compound heterozygous for c.1009C>G (p.Arg337Gly) and a splice site variant c.1259+5G>T.
29304374	1	73	theme	Golgi-localized	140:154	arg1	essential					188:196	essential	188:196	essential	188:196	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	1	73	theme	Golgi-localized	140:154	arg1	process					272:278	a process	270:278	a process known as "core fucosylation	270:306	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	1	73	theme	Golgi-localized	140:154	arg1	Fucosyltransferase					102:119	Fucosyltransferase 8	102:121	Fucosyltransferase 8 (FUT8)	102:128	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	1	73	theme	Golgi-localized	140:154	arg1	fucosyltransferase					161:178	a Golgi-localized α1,6 fucosyltransferase	138:178	a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins	138:267	Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation."
29304374	7	74	theme	FUT8	1145:1148	arg1	expression					1158:1167	FUT8 protein expression	1145:1167	FUT8 protein expression	1145:1167	Functional studies using primary fibroblasts from two affected individuals revealed a complete lack of FUT8 protein expression that ultimately resulted in substantial deficiencies in total core fucosylated N-glycans.
29454068	11	0	theme	Genetic	1393:1399	arg1	ablation					1401:1408	Genetic ablation	1393:1408	Genetic ablation of RACK1 O-GlcNAcylation at Ser122	1393:1443	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	5	1	theme	spectrometry	655:666	arg1	analysis					668:675	mass spectrometry analysis	650:675	mass spectrometry analysis	650:675	METHODS: The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry analysis.
29454068	11	2	theme	mouse	1566:1570	arg1	model					1572:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	8	3	theme	RACK1	973:977	arg1	O-GlcNAcylation					979:993	RACK1 O-GlcNAcylation	973:993	RACK1 O-GlcNAcylation	973:993	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples.
29454068	15	4	theme	protein	2133:2139	arg1	PKCβII					2149:2154	PKCβII	2149:2154	PKCβII	2149:2154	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	4	theme	protein	2133:2139	arg1	kinase					2141:2146	the protein kinase	2129:2146	the protein kinase	2129:2146	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	6	5	theme	tumor	812:816	arg1	cells					818:822	tumor cells	812:822	tumor cells	812:822	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	7	6	used	used	864:867	arg2	mice					854:857	Transgenic knock-in mice	834:857	Transgenic knock-in mice	834:857	Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo.
29454068	11	7	theme	O-GlcNAcylation	1419:1433	arg1	ablation					1401:1408	Genetic ablation	1393:1408	Genetic ablation of RACK1 O-GlcNAcylation at Ser122	1393:1443	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	15	8	dep	SUMMARY	1962:1968	arg1	promotes					2062:2069	promotes	2062:2069	promotes	2062:2069	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	6	9	theme	behaviors	799:807	arg1	translation					762:772	the translation	758:772	the translation of oncogenic factors and behaviors of tumor cells	758:822	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	13	10	theme	O-GlcNAc	1805:1812	arg1	metabolism					1814:1823	O-GlcNAc metabolism	1805:1823	O-GlcNAc metabolism	1805:1823	CONCLUSIONS: These findings demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis.
29454068	6	11	theme	factors	787:793	arg1	translation					762:772	the translation	758:772	the translation of oncogenic factors and behaviors of tumor cells	758:822	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	7	12	theme	Transgenic	834:843	arg1	mice					854:857	Transgenic knock-in mice	834:857	Transgenic knock-in mice	834:857	Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo.
29454068	12	13	theme	HCC	1632:1634	arg1	samples					1644:1650	HCC patient samples	1632:1650	HCC patient samples	1632:1650	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	3	14	theme	previous	315:322	arg1	study					324:328	Our previous study	311:328	Our previous study	311:328	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	9	15	mod	modified	1119:1126	arg3	O-GlcNAc					1131:1138	O-GlcNAc	1131:1138	O-GlcNAc	1131:1138	RESULTS: We found that ribosomal RACK1 was highly modified by O-GlcNAc at Ser122.
29454068	9	15	mod	modified	1119:1126	arg1	RACK1					1102:1106	ribosomal RACK1	1092:1106	ribosomal RACK1	1092:1106	RESULTS: We found that ribosomal RACK1 was highly modified by O-GlcNAc at Ser122.
29454068	15	16	theme	ribosomal	1990:1998	arg1	receptor					2000:2007	ribosomal receptor	1990:2007	ribosomal receptor for activated C-kinase 1	1990:2032	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	17	with	localization	2095:2106	arg1	PKCβII					2149:2154	PKCβII	2149:2154	PKCβII	2149:2154	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	17	with	localization	2095:2106	arg1	kinase					2141:2146	the protein kinase	2129:2146	the protein kinase	2129:2146	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	18	theme	carcinoma	2235:2243	arg1	translation					2174:2184	the translation	2170:2184	the translation of oncogenes	2170:2197	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	18	theme	carcinoma	2235:2243	arg1	tumorigenesis					2203:2215	tumorigenesis	2203:2215	tumorigenesis	2203:2215	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	3	19	theme	ribosomal	345:353	arg1	C-kinase					378:385	ribosomal receptor for activated C-kinase 1	345:387	ribosomal receptor for activated C-kinase 1 (RACK1)	345:395	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	3	19	theme	ribosomal	345:353	arg1	RACK1					390:394	RACK1	390:394	RACK1	390:394	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	4	20	theme	study	484:488	arg1	aim					472:474	The aim	468:474	The aim of this study	468:488	The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis.
29454068	16	21	theme	ribosomal	2275:2283	arg1	receptor					2285:2292	ribosomal receptor	2275:2292	ribosomal receptor	2275:2292	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	12	22	gly	O-GlcNAcylation	1595:1609	arg1	samples					1644:1650	HCC patient samples	1632:1650	HCC patient samples	1632:1650	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	1	23	theme	O-linked	132:139	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	23	theme	O-linked	132:139	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	23	theme	O-linked	132:139	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	23	theme	O-linked	132:139	arg1	O-GlcNAcylation					170:184	O-GlcNAcylation	170:184	O-GlcNAcylation	170:184	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	10	24	from	phosphorylation	1327:1341	arg1	cells					1386:1390	HCC cells	1382:1390	HCC cells	1382:1390	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	12	25	located	observed	1620:1627	arg2	O-GlcNAcylation					1595:1609	Increased RACK1 O-GlcNAcylation	1579:1609	Increased RACK1 O-GlcNAcylation	1579:1609	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	12	25	located	observed	1620:1627	arg1	samples					1644:1650	HCC patient samples	1632:1650	HCC patient samples	1632:1650	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	14	26	theme	promising	1921:1929	arg1	options					1931:1937	promising options	1921:1937	promising options for HCC treatment	1921:1955	Targeting RACK1 O-GlcNAcylation provides promising options for HCC treatment.
29454068	12	27	theme	RACK1	1589:1593	arg1	O-GlcNAcylation					1595:1609	Increased RACK1 O-GlcNAcylation	1579:1609	Increased RACK1 O-GlcNAcylation	1579:1609	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	3	28	theme	for	364:366	arg1	C-kinase					378:385	ribosomal receptor for activated C-kinase 1	345:387	ribosomal receptor for activated C-kinase 1 (RACK1)	345:395	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	3	28	theme	for	364:366	arg1	RACK1					390:394	RACK1	390:394	RACK1	390:394	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	15	29	theme	acid	2047:2050	arg1	serine122					2052:2060	the amino acid serine122	2037:2060	the amino acid serine122	2037:2060	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	1	30	theme	general	191:197	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	30	theme	general	191:197	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	30	theme	general	191:197	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	4	31	theme	O-GlcNAcylation	522:536	arg1	role					508:511	the role	504:511	the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis	504:583	The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis.
29454068	11	32	theme	-induced	1553:1560	arg1	model					1572:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	8	33	theme	clinical	1047:1054	arg1	samples					1060:1066	clinical HCC samples	1047:1066	clinical HCC samples	1047:1066	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples.
29454068	5	34	theme	RACK1	610:614	arg1	s					604:604	The site(s)	595:605	The site(s) of RACK1 for O-GlcNAcylation	595:634	METHODS: The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry analysis.
29454068	6	35	theme	cell	682:685	arg1	lines					687:691	HCC cell lines	678:691	HCC cell lines	678:691	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	10	36	with	stability	1197:1205	arg1	PKCβII					1246:1251	PKCβII	1246:1251	PKCβII (PRKCB)	1246:1259	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	36	with	stability	1197:1205	arg1	PRKCB					1254:1258	PRKCB	1254:1258	PRKCB	1254:1258	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	37	theme	eukaryotic	1283:1292	arg1	4E					1324:1325	eukaryotic translation initiation factor 4E	1283:1325	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	1	38	theme	Aberrant	84:91	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	38	theme	Aberrant	84:91	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	38	theme	Aberrant	84:91	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	15	39	theme	activated	2013:2021	arg1	C-kinase					2023:2030	activated C-kinase 1	2013:2032	activated C-kinase 1	2013:2032	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	9	40	theme	ribosomal	1092:1100	arg1	RACK1					1102:1106	ribosomal RACK1	1092:1106	ribosomal RACK1	1092:1106	RESULTS: We found that ribosomal RACK1 was highly modified by O-GlcNAc at Ser122.
29454068	14	41	theme	RACK1	1890:1894	arg1	O-GlcNAcylation					1896:1910	Targeting RACK1 O-GlcNAcylation	1880:1910	Targeting RACK1 O-GlcNAcylation	1880:1910	Targeting RACK1 O-GlcNAcylation provides promising options for HCC treatment.
29454068	7	42	theme	HCC	927:929	arg1	tumorigenesis					931:943	HCC tumorigenesis	927:943	HCC tumorigenesis	927:943	Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo.
29454068	1	43	theme	mRNA	103:106	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	43	theme	mRNA	103:106	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	43	theme	mRNA	103:106	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	10	44	theme	4E	1324:1325	arg1	phosphorylation					1327:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	0	45	theme	RACK1	19:23	arg1	O-GlcNAcylation					0:14	O-GlcNAcylation	0:14	O-GlcNAcylation of RACK1	0:23	O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis.
29454068	10	46	with	interaction	1229:1239	arg1	PKCβII					1246:1251	PKCβII	1246:1251	PKCβII (PRKCB)	1246:1259	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	46	with	interaction	1229:1239	arg1	PRKCB					1254:1258	PRKCB	1254:1258	PRKCB	1254:1258	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	6	47	theme	HCC	678:680	arg1	lines					687:691	HCC cell lines	678:691	HCC cell lines	678:691	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	10	48	from	oncogenes	1369:1377	arg1	cells					1386:1390	HCC cells	1382:1390	HCC cells	1382:1390	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	15	49	theme	ribosome	2086:2093	arg1	localization					2095:2106	ribosome localization	2086:2106	ribosome localization	2086:2106	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	10	50	theme	initiation	1306:1315	arg1	4E					1324:1325	eukaryotic translation initiation factor 4E	1283:1325	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	0	51	theme	hepatocellular	34:47	arg1	carcinogenesis					49:62	hepatocellular carcinogenesis	34:62	hepatocellular carcinogenesis	34:62	O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis.
29454068	10	52	theme	RACK1	1170:1174	arg1	O-GlcNAcylation					1151:1165	O-GlcNAcylation	1151:1165	O-GlcNAcylation of RACK1	1151:1174	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	13	53	theme	HCC	1861:1863	arg1	tumorigenesis					1865:1877	HCC tumorigenesis	1861:1877	HCC tumorigenesis	1861:1877	CONCLUSIONS: These findings demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis.
29454068	3	54	theme	hepatocellular	436:449	arg1	carcinoma					451:459	hepatocellular carcinoma	436:459	hepatocellular carcinoma (HCC)	436:465	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	3	54	theme	hepatocellular	436:449	arg1	HCC					462:464	HCC	462:464	HCC	462:464	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	4	55	theme	oncogene	541:548	arg1	translation					550:560	oncogene translation	541:560	oncogene translation	541:560	The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis.
29454068	11	56	from	metastasis	1502:1511	arg1	model					1572:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	11	56	from	metastasis	1502:1511	arg1	vitro					1516:1520	vitro	1516:1520	vitro	1516:1520	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	16	57	theme	activated	2298:2306	arg1	C-kinase					2308:2315	activated C-kinase 1	2298:2317	activated C-kinase 1	2298:2317	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	10	58	theme	HCC	1382:1384	arg1	cells					1386:1390	HCC cells	1382:1390	HCC cells	1382:1390	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	7	59	theme	O-GlcNAcylation	897:911	arg1	role					883:886	the role	879:886	the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo	879:951	Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo.
29454068	1	60	theme	BACKGROUND	65:74	arg1	AIMS					78:81	BACKGROUND & AIMS	65:81	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.	65:228	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	6	61	from	effects	722:728	arg1	translation					762:772	the translation	758:772	the translation of oncogenic factors and behaviors of tumor cells	758:822	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	2	62	dep	whether	244:250	arg1	interlinked					283:293	interlinked	283:293	are interlinked	279:293	Nevertheless, whether and how these two pathways are interlinked remain unknown.
29454068	5	63	theme	mass	650:653	arg1	analysis					668:675	mass spectrometry analysis	650:675	mass spectrometry analysis	650:675	METHODS: The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry analysis.
29454068	10	64	theme	oncogenes	1369:1377	arg1	translation					1347:1357	translation	1347:1357	translation	1347:1357	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	64	theme	oncogenes	1369:1377	arg1	phosphorylation					1327:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	16	65	theme	receptor	2285:2292	arg1	O-GlcNAcylation					2256:2270	Increased O-GlcNAcylation	2246:2270	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1	2246:2317	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	8	66	theme	O-GlcNAcylation	979:993	arg1	correlation					958:968	The correlation	954:968	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse	954:1028	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples.
29454068	13	67	theme	cap-dependent	1828:1840	arg1	translation					1842:1852	cap-dependent translation	1828:1852	cap-dependent translation	1828:1852	CONCLUSIONS: These findings demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis.
29454068	6	68	theme	cells	818:822	arg1	behaviors					799:807	behaviors	799:807	behaviors of tumor cells	799:822	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	6	68	theme	cells	818:822	arg1	factors					787:793	oncogenic factors	777:793	oncogenic factors	777:793	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	10	69	theme	ribosome	1208:1215	arg1	binding					1217:1223	ribosome binding	1208:1223	ribosome binding	1208:1223	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	8	70	theme	tumor	1000:1004	arg1	progression					1006:1016	tumor progression	1000:1016	tumor progression	1000:1016	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples.
29454068	11	71	theme	RACK1	1413:1417	arg1	O-GlcNAcylation					1419:1433	RACK1 O-GlcNAcylation	1413:1433	RACK1 O-GlcNAcylation	1413:1433	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	16	72	from	recurrence	2378:2387	arg1	patients					2392:2399	patients	2392:2399	patients with hepatocellular carcinoma	2392:2429	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	4	73	from	role	508:511	arg1	translation					550:560	oncogene translation	541:560	oncogene translation	541:560	The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis.
29454068	4	73	from	role	508:511	arg1	carcinogenesis					570:583	HCC carcinogenesis	566:583	HCC carcinogenesis	566:583	The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis.
29454068	11	74	theme	HCC	1562:1564	arg1	model					1572:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	15	75	theme	receptor	2000:2007	arg1	O-GlcNAcylation					1971:1985	O-GlcNAcylation	1971:1985	O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122	1971:2060	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	76	with	stability	2075:2083	arg1	PKCβII					2149:2154	PKCβII	2149:2154	PKCβII	2149:2154	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	76	with	stability	2075:2083	arg1	kinase					2141:2146	the protein kinase	2129:2146	the protein kinase	2129:2146	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	12	77	theme	patient	1636:1642	arg1	samples					1644:1650	HCC patient samples	1632:1650	HCC patient samples	1632:1650	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	16	78	theme	Increased	2246:2254	arg1	O-GlcNAcylation					2256:2270	Increased O-GlcNAcylation	2246:2270	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1	2246:2317	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	6	79	theme	oncogenic	777:785	arg1	factors					787:793	oncogenic factors	777:793	oncogenic factors	777:793	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	7	80	theme	knock-in	845:852	arg1	mice					854:857	Transgenic knock-in mice	834:857	Transgenic knock-in mice	834:857	Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo.
29454068	15	81	theme	hepatocellular	2220:2233	arg1	carcinoma					2235:2243	hepatocellular carcinoma	2220:2243	hepatocellular carcinoma	2220:2243	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	13	82	theme	key	1784:1786	arg1	mediator					1788:1795	key mediator	1784:1795	key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis	1784:1877	CONCLUSIONS: These findings demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis.
29454068	11	83	from	Ser122	1438:1443	arg1	ablation					1401:1408	Genetic ablation	1393:1408	Genetic ablation of RACK1 O-GlcNAcylation at Ser122	1393:1443	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	1	84	theme	protein	124:130	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	84	theme	protein	124:130	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	84	theme	protein	124:130	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	84	theme	protein	124:130	arg1	O-GlcNAcylation					170:184	O-GlcNAcylation	170:184	O-GlcNAcylation	170:184	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	3	85	theme	receptor	355:362	arg1	C-kinase					378:385	ribosomal receptor for activated C-kinase 1	345:387	ribosomal receptor for activated C-kinase 1 (RACK1)	345:395	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	3	85	theme	receptor	355:362	arg1	RACK1					390:394	RACK1	390:394	RACK1	390:394	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	16	86	theme	hepatocellular	2406:2419	arg1	carcinoma					2421:2429	hepatocellular carcinoma	2406:2429	hepatocellular carcinoma	2406:2429	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	15	87	from	serine122	2052:2060	arg1	O-GlcNAcylation					1971:1985	O-GlcNAcylation	1971:1985	O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122	1971:2060	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	16	88	from	growth	2355:2360	arg1	patients					2392:2399	patients	2392:2399	patients with hepatocellular carcinoma	2392:2429	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	14	89	theme	HCC	1943:1945	arg1	treatment					1947:1955	HCC treatment	1943:1955	HCC treatment	1943:1955	Targeting RACK1 O-GlcNAcylation provides promising options for HCC treatment.
29454068	12	90	theme	Increased	1579:1587	arg1	O-GlcNAcylation					1595:1609	Increased RACK1 O-GlcNAcylation	1579:1609	Increased RACK1 O-GlcNAcylation	1579:1609	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	1	91	dep	AIMS	78:81	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	91	dep	AIMS	78:81	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	91	dep	AIMS	78:81	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	4	92	theme	RACK1	516:520	arg1	O-GlcNAcylation					522:536	RACK1 O-GlcNAcylation	516:536	RACK1 O-GlcNAcylation	516:536	The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis.
29454068	16	93	from	metastasis	2363:2372	arg1	patients					2392:2399	patients	2392:2399	patients with hepatocellular carcinoma	2392:2429	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	3	94	theme	activated	368:376	arg1	C-kinase					378:385	ribosomal receptor for activated C-kinase 1	345:387	ribosomal receptor for activated C-kinase 1 (RACK1)	345:395	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	3	94	theme	activated	368:376	arg1	RACK1					390:394	RACK1	390:394	RACK1	390:394	Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC).
29454068	8	95	theme	HCC	1056:1058	arg1	samples					1060:1066	clinical HCC samples	1047:1066	clinical HCC samples	1047:1066	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples.
29454068	1	96	theme	&	76:76	arg1	AIMS					78:81	BACKGROUND & AIMS	65:81	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.	65:228	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	15	97	theme	amino	2041:2045	arg1	serine122					2052:2060	the amino acid serine122	2037:2060	the amino acid serine122	2037:2060	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	10	98	theme	translation	1294:1304	arg1	4E					1324:1325	eukaryotic translation initiation factor 4E	1283:1325	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	16	99	with	patients	2392:2399	arg1	carcinoma					2421:2429	hepatocellular carcinoma	2406:2429	hepatocellular carcinoma	2406:2429	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	10	100	from	translation	1347:1357	arg1	cells					1386:1390	HCC cells	1382:1390	HCC cells	1382:1390	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	101	theme	increased	1273:1281	arg1	phosphorylation					1327:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	5	102	theme	site	599:602	arg1	s					604:604	The site(s)	595:605	The site(s) of RACK1 for O-GlcNAcylation	595:634	METHODS: The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry analysis.
29454068	1	103	theme	oncogenic	93:101	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	103	theme	oncogenic	93:101	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	103	theme	oncogenic	93:101	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	14	104	theme	Targeting	1880:1888	arg1	O-GlcNAcylation					1896:1910	Targeting RACK1 O-GlcNAcylation	1880:1910	Targeting RACK1 O-GlcNAcylation	1880:1910	Targeting RACK1 O-GlcNAcylation provides promising options for HCC treatment.
29454068	6	105	theme	RACK1	733:737	arg1	O-GlcNAcylation					739:753	RACK1 O-GlcNAcylation	733:753	RACK1 O-GlcNAcylation	733:753	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	10	106	with	binding	1217:1223	arg1	PKCβII					1246:1251	PKCβII	1246:1251	PKCβII (PRKCB)	1246:1259	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	106	with	binding	1217:1223	arg1	PRKCB					1254:1258	PRKCB	1254:1258	PRKCB	1254:1258	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	107	theme	factor	1317:1322	arg1	4E					1324:1325	eukaryotic translation initiation factor 4E	1283:1325	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	16	108	theme	tumor	2349:2353	arg1	growth					2355:2360	tumor growth	2349:2360	tumor growth	2349:2360	Increased O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 is positively correlated with tumor growth, metastasis and recurrence in patients with hepatocellular carcinoma.
29454068	11	109	from	angiogenesis	1484:1495	arg1	model					1572:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	11	109	from	angiogenesis	1484:1495	arg1	vitro					1516:1520	vitro	1516:1520	vitro	1516:1520	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	12	110	theme	tumor	1672:1676	arg1	development					1678:1688	tumor development	1672:1688	tumor development	1672:1688	Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy.
29454068	10	111	from	cells	1386:1390	arg1	translation					1347:1357	translation	1347:1357	translation	1347:1357	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	10	111	from	cells	1386:1390	arg1	phosphorylation					1327:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	increased eukaryotic translation initiation factor 4E phosphorylation	1273:1341	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	8	112	with	correlation	958:968	arg1	relapse					1022:1028	relapse	1022:1028	relapse	1022:1028	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples.
29454068	8	112	with	correlation	958:968	arg1	progression					1006:1016	tumor progression	1000:1016	tumor progression	1000:1016	The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples.
29454068	10	113	theme	potent	1362:1367	arg1	oncogenes					1369:1377	potent oncogenes	1362:1377	potent oncogenes in HCC cells	1362:1390	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	15	114	theme	oncogenes	2189:2197	arg1	translation					2174:2184	the translation	2170:2184	the translation of oncogenes	2170:2197	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	114	theme	oncogenes	2189:2197	arg1	tumorigenesis					2203:2215	tumorigenesis	2203:2215	tumorigenesis	2203:2215	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	4	115	theme	HCC	566:568	arg1	carcinogenesis					570:583	HCC carcinogenesis	566:583	HCC carcinogenesis	566:583	The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis.
29454068	1	116	link	O-linked	132:139	arg1	β-N-acetylglucosaminylation					141:167	protein O-linked β-N-acetylglucosaminylation	124:167	protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation)	124:185	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	116	link	O-linked	132:139	arg1	features					199:206	general features	191:206	general features	191:206	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	116	link	O-linked	132:139	arg1	translation					108:118	Aberrant oncogenic mRNA translation	84:118	Aberrant oncogenic mRNA translation	84:118	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	1	116	link	O-linked	132:139	arg1	O-GlcNAcylation					170:184	O-GlcNAcylation	170:184	O-GlcNAcylation	170:184	BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis.
29454068	6	117	theme	O-GlcNAcylation	739:753	arg1	effects					722:728	the effects	718:728	the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells	718:822	HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro.
29454068	7	118	theme	RACK1	891:895	arg1	O-GlcNAcylation					897:911	RACK1 O-GlcNAcylation	891:911	RACK1 O-GlcNAcylation	891:911	Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo.
29454068	10	119	theme	protein	1189:1195	arg1	stability					1197:1205	protein stability	1189:1205	protein stability	1189:1205	O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells.
29454068	15	120	with	interaction	2112:2122	arg1	PKCβII					2149:2154	PKCβII	2149:2154	PKCβII	2149:2154	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	15	120	with	interaction	2112:2122	arg1	kinase					2141:2146	the protein kinase	2129:2146	the protein kinase	2129:2146	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29454068	11	121	from	tumorigenesis	1469:1481	arg1	model					1572:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	diethylnitrosamine (DEN)-induced HCC mouse model	1529:1576	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	11	121	from	tumorigenesis	1469:1481	arg1	vitro					1516:1520	vitro	1516:1520	vitro	1516:1520	Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model.
29454068	15	122	theme	LAY	1958:1960	arg1	SUMMARY					1962:1968	LAY SUMMARY	1958:1968	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.	1958:2244	LAY SUMMARY: O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction with the protein kinase, PKCβII, thus driving the translation of oncogenes and tumorigenesis of hepatocellular carcinoma.
29980609	7	0	theme	AICL	1289:1292	arg1	domain					1313:1318	the AICL C-type lectin-like domain	1285:1318	the AICL C-type lectin-like domain	1285:1318	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	3	1	theme	NK	678:679	arg1	fratricide					681:690	NKp80-mediated NK fratricide	663:690	NKp80-mediated NK fratricide	663:690	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	1	2	theme	human	261:265	arg1	cells					270:274	virtually all mature human NK cells	240:274	virtually all mature human NK cells	240:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	7	3	from	domain	1313:1318	arg1	atypical					1221:1228	atypical	1221:1228	atypical	1221:1228	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	7	4	link	N-linked	1253:1260	arg1	sites					1276:1280	three conventional N-linked glycosylation sites	1234:1280	three conventional N-linked glycosylation sites	1234:1280	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	1	5	theme	C-type	183:188	arg1	receptor					202:209	the C-type lectin-like receptor NKp80	179:215	the C-type lectin-like receptor NKp80	179:215	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	9	6	theme	impaired	1777:1784	arg1	expression					1791:1800	the impaired AICL expression	1773:1800	the impaired AICL expression in calnexin-deficient cells	1773:1828	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	6	7	theme	proteasomal	1192:1202	arg1	degradation					1204:1214	proteasomal degradation	1192:1214	proteasomal degradation	1192:1214	In contrast, cytoplasmic lysines act as negative regulators targeting AICL for proteasomal degradation.
29980609	1	8	theme	receptor	202:209	arg1	glycoproteins					123:135	AICL glycoproteins	118:135	AICL glycoproteins	118:135	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	8	theme	receptor	202:209	arg1	ligands					168:174	cognate activation-induced ligands	141:174	cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells	141:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	7	9	gly	glycosylation	1403:1415	arg1	site					1460:1463	at least one conventional glycosylation site	1420:1463	at least one conventional glycosylation site	1420:1463	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	7	10	theme	site	1460:1463	arg1	glycosylation					1403:1415	glycosylation	1403:1415	glycosylation of at least one conventional glycosylation site	1403:1463	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	9	11	theme	AICL	1663:1666	arg1	expression					1676:1685	AICL surface expression	1663:1685	AICL surface expression	1663:1685	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	3	12	theme	resting	547:553	arg1	cells					558:562	resting NK cells	547:562	resting NK cells	547:562	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	7	13	gly	glycosylation	1446:1458	arg2	site					1460:1463	at least one conventional glycosylation site	1420:1463	at least one conventional glycosylation site	1420:1463	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	7	13	gly	glycosylation	1446:1458	arg2	one					1429:1431	one	1429:1431	one	1429:1431	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	5	14	gly	glycoproteins	951:963	arg1	glycoproteins					951:963	AICL glycoproteins	946:963	AICL glycoproteins	946:963	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	8	15	theme	conventional	1498:1509	arg1	glycosylation					1520:1532	conventional N-linked glycosylation	1498:1532	conventional N-linked glycosylation	1498:1532	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	7	16	theme	conventional	1433:1444	arg1	site					1460:1463	at least one conventional glycosylation site	1420:1463	at least one conventional glycosylation site	1420:1463	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	1	17	gly	glycoproteins	123:135	arg1	glycoproteins					123:135	AICL glycoproteins	118:135	AICL glycoproteins	118:135	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	17	gly	glycoproteins	123:135	arg1	ligands					168:174	cognate activation-induced ligands	141:174	cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells	141:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	3	18	theme	NK	577:578	arg1	cells					580:584	NK cells	577:584	NK cells	577:584	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	8	19	theme	glycosylation	1520:1532	arg1	extent					1488:1493	the extent	1484:1493	the extent of conventional N-linked glycosylation	1484:1532	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	5	20	theme	homodimers	1060:1069	arg1	expression					1041:1050	efficient cell surface expression	1018:1050	efficient cell surface expression of AICL homodimers	1018:1069	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	1	21	theme	AICL	118:121	arg1	glycoproteins					123:135	AICL glycoproteins	118:135	AICL glycoproteins	118:135	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	21	theme	AICL	118:121	arg1	ligands					168:174	cognate activation-induced ligands	141:174	cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells	141:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	10	22	theme	posttranslational	1956:1972	arg1	mechanisms					1974:1983	several independent cellular posttranslational mechanisms	1927:1983	several independent cellular posttranslational mechanisms	1927:1983	Collectively, our data demonstrate that AICL expression and surfacing are tightly controlled by several independent cellular posttranslational mechanisms.
29980609	5	23	theme	glycoproteins	951:963	arg1	homodimerization					926:941	stable homodimerization	919:941	stable homodimerization of AICL glycoproteins	919:963	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	2	24	theme	human	487:491	arg1	cells					496:500	human NK cells	487:500	human NK cells	487:500	Notably, AICL and NKp80 are encoded by adjacent genes in the NK gene complex and are coexpressed by human NK cells.
29980609	8	25	theme	AICL	1561:1564	arg1	expression					1574:1583	AICL surface expression	1561:1583	AICL surface expression	1561:1583	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	4	26	gly	glycoproteins	755:767	arg1	glycoproteins					755:767	AICL glycoproteins	750:767	AICL glycoproteins	750:767	In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression.
29980609	10	27	theme	independent	1935:1945	arg1	mechanisms					1974:1983	several independent cellular posttranslational mechanisms	1927:1983	several independent cellular posttranslational mechanisms	1927:1983	Collectively, our data demonstrate that AICL expression and surfacing are tightly controlled by several independent cellular posttranslational mechanisms.
29980609	1	28	theme	activation-induced	149:166	arg1	glycoproteins					123:135	AICL glycoproteins	118:135	AICL glycoproteins	118:135	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	28	theme	activation-induced	149:166	arg1	ligands					168:174	cognate activation-induced ligands	141:174	cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells	141:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	5	29	theme	stable	919:924	arg1	homodimerization					926:941	stable homodimerization	919:941	stable homodimerization of AICL glycoproteins	919:963	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	4	30	theme	glycoproteins	755:767	arg1	determinants					734:745	molecular determinants	724:745	molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression	724:847	In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression.
29980609	0	31	theme	Activating	88:97	arg1	Receptor					102:109	the Activating NK Receptor NKp80	84:115	the Activating NK Receptor NKp80	84:115	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	8	32	theme	glycosylation	1599:1611	arg1	site					1613:1616	the atypical glycosylation site	1586:1616	the atypical glycosylation site	1586:1616	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	0	33	theme	Receptor	102:109	arg1	Surfacing					32:40	Surfacing	32:40	Surfacing of AICL Glycoproteins	32:62	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	0	33	theme	Receptor	102:109	arg1	Ligands					73:79	Cognate Ligands	65:79	Cognate Ligands of the Activating NK Receptor NKp80	65:115	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	7	34	from	atypical	1221:1228	arg1	domain					1313:1318	the AICL C-type lectin-like domain	1285:1318	the AICL C-type lectin-like domain	1285:1318	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	4	35	theme	molecular	724:732	arg1	determinants					734:745	molecular determinants	724:745	molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression	724:847	In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression.
29980609	0	36	theme	Cellular	0:7	arg1	Mechanisms					9:18	Cellular Mechanisms	0:18	Cellular Mechanisms	0:18	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	5	37	theme	disulfide	968:976	arg1	bonding					978:984	disulfide bonding	968:984	disulfide bonding	968:984	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	10	38	theme	cellular	1947:1954	arg1	mechanisms					1974:1983	several independent cellular posttranslational mechanisms	1927:1983	several independent cellular posttranslational mechanisms	1927:1983	Collectively, our data demonstrate that AICL expression and surfacing are tightly controlled by several independent cellular posttranslational mechanisms.
29980609	1	39	theme	NKp80-AICL	281:290	arg1	interaction					292:302	NKp80-AICL interaction	281:302	NKp80-AICL interaction	281:302	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	9	40	theme	expression	1676:1685	arg1	control					1652:1658	Stringent control	1642:1658	Stringent control of AICL surface expression by glycosylation	1642:1702	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	1	41	theme	cognate	141:147	arg1	glycoproteins					123:135	AICL glycoproteins	118:135	AICL glycoproteins	118:135	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	41	theme	cognate	141:147	arg1	ligands					168:174	cognate activation-induced ligands	141:174	cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells	141:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	4	42	theme	AICL	825:828	arg1	expression					838:847	AICL surface expression	825:847	AICL surface expression	825:847	In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression.
29980609	9	43	with	expression	1791:1800	arg1	calnexin					1760:1767	calnexin	1760:1767	calnexin	1760:1767	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	2	44	theme	gene	451:454	arg1	complex					456:462	the NK gene complex	444:462	the NK gene complex	444:462	Notably, AICL and NKp80 are encoded by adjacent genes in the NK gene complex and are coexpressed by human NK cells.
29980609	0	45	theme	Cognate	65:71	arg1	Surfacing					32:40	Surfacing	32:40	Surfacing of AICL Glycoproteins	32:62	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	0	45	theme	Cognate	65:71	arg1	Ligands					73:79	Cognate Ligands	65:79	Cognate Ligands of the Activating NK Receptor NKp80	65:115	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	0	46	theme	Glycoproteins	50:62	arg1	Surfacing					32:40	Surfacing	32:40	Surfacing of AICL Glycoproteins	32:62	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	0	46	theme	Glycoproteins	50:62	arg1	Ligands					73:79	Cognate Ligands	65:79	Cognate Ligands of the Activating NK Receptor NKp80	65:115	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	1	47	theme	cell	318:321	arg1	functions					332:340	NK cell effector functions	315:340	NK cell effector functions such as cytotoxicity and cytokine secretion	315:384	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	47	theme	cell	318:321	arg1	cytotoxicity					350:361	cytotoxicity	350:361	cytotoxicity	350:361	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	47	theme	cell	318:321	arg1	secretion					376:384	cytokine secretion	367:384	cytokine secretion	367:384	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	5	48	theme	AICL	1055:1058	arg1	homodimers					1060:1069	AICL homodimers	1055:1069	AICL homodimers	1055:1069	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	6	49	theme	negative	1153:1160	arg1	lysines					1138:1144	cytoplasmic lysines	1126:1144	cytoplasmic lysines	1126:1144	In contrast, cytoplasmic lysines act as negative regulators targeting AICL for proteasomal degradation.
29980609	6	49	theme	negative	1153:1160	arg1	regulators					1162:1171	negative regulators	1153:1171	negative regulators targeting AICL for proteasomal degradation	1153:1214	In contrast, cytoplasmic lysines act as negative regulators targeting AICL for proteasomal degradation.
29980609	3	50	theme	NKp80-mediated	663:676	arg1	fratricide					681:690	NKp80-mediated NK fratricide	663:690	NKp80-mediated NK fratricide	663:690	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	5	51	theme	C-type	876:881	arg1	domain					895:900	the C-type lectin-like domain	872:900	the C-type lectin-like domain	872:900	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	5	52	theme	cell	1028:1031	arg1	expression					1041:1050	efficient cell surface expression	1018:1050	efficient cell surface expression of AICL homodimers	1018:1069	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	6	53	theme	cytoplasmic	1126:1136	arg1	lysines					1138:1144	cytoplasmic lysines	1126:1144	cytoplasmic lysines	1126:1144	In contrast, cytoplasmic lysines act as negative regulators targeting AICL for proteasomal degradation.
29980609	6	53	theme	cytoplasmic	1126:1136	arg1	regulators					1162:1171	negative regulators	1153:1171	negative regulators targeting AICL for proteasomal degradation	1153:1214	In contrast, cytoplasmic lysines act as negative regulators targeting AICL for proteasomal degradation.
29980609	1	54	theme	mature	254:259	arg1	cells					270:274	virtually all mature human NK cells	240:274	virtually all mature human NK cells	240:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	9	55	theme	AICL	1750:1753	arg1	expression					1791:1800	the impaired AICL expression	1773:1800	the impaired AICL expression in calnexin-deficient cells	1773:1828	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	9	55	theme	AICL	1750:1753	arg1	interaction					1735:1745	the pronounced interaction	1720:1745	the pronounced interaction of AICL with calnexin	1720:1767	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	7	56	theme	C-type	1294:1299	arg1	domain					1313:1318	the AICL C-type lectin-like domain	1285:1318	the AICL C-type lectin-like domain	1285:1318	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	10	57	theme	AICL	1871:1874	arg1	expression					1876:1885	AICL expression	1871:1885	AICL expression	1871:1885	Collectively, our data demonstrate that AICL expression and surfacing are tightly controlled by several independent cellular posttranslational mechanisms.
29980609	1	58	theme	NK	267:268	arg1	cells					270:274	virtually all mature human NK cells	240:274	virtually all mature human NK cells	240:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	59	theme	lectin-like	190:200	arg1	receptor					202:209	the C-type lectin-like receptor NKp80	179:215	the C-type lectin-like receptor NKp80	179:215	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	3	60	theme	NK	555:556	arg1	cells					558:562	resting NK cells	547:562	resting NK cells	547:562	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	5	61	theme	lectin-like	883:893	arg1	domain					895:900	the C-type lectin-like domain	872:900	the C-type lectin-like domain	872:900	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	9	62	theme	AICL	1786:1789	arg1	expression					1791:1800	the impaired AICL expression	1773:1800	the impaired AICL expression in calnexin-deficient cells	1773:1828	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	8	63	theme	N-linked	1511:1518	arg1	glycosylation					1520:1532	conventional N-linked glycosylation	1498:1532	conventional N-linked glycosylation	1498:1532	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	10	64	theme	several	1927:1933	arg1	mechanisms					1974:1983	several independent cellular posttranslational mechanisms	1927:1983	several independent cellular posttranslational mechanisms	1927:1983	Collectively, our data demonstrate that AICL expression and surfacing are tightly controlled by several independent cellular posttranslational mechanisms.
29980609	7	65	theme	glycosylation	1446:1458	arg1	site					1460:1463	at least one conventional glycosylation site	1420:1463	at least one conventional glycosylation site	1420:1463	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	7	66	theme	conventional	1240:1251	arg1	sites					1276:1280	three conventional N-linked glycosylation sites	1234:1280	three conventional N-linked glycosylation sites	1234:1280	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	3	67	theme	proinflammatory	589:603	arg1	cytokines					605:613	proinflammatory cytokines	589:613	proinflammatory cytokines	589:613	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	5	68	theme	AICL	946:949	arg1	glycoproteins					951:963	AICL glycoproteins	946:963	AICL glycoproteins	946:963	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	8	69	theme	surface	1566:1572	arg1	expression					1574:1583	AICL surface expression	1561:1583	AICL surface expression	1561:1583	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	3	70	theme	cells	580:584	arg1	exposure					565:572	exposure	565:572	exposure of NK cells to proinflammatory cytokines	565:613	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	8	71	gly	glycosylation	1599:1611	arg2	site					1613:1616	the atypical glycosylation site	1586:1616	the atypical glycosylation site	1586:1616	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	2	72	from	genes	435:439	arg1	complex					456:462	the NK gene complex	444:462	the NK gene complex	444:462	Notably, AICL and NKp80 are encoded by adjacent genes in the NK gene complex and are coexpressed by human NK cells.
29980609	7	73	theme	N-linked	1253:1260	arg1	sites					1276:1280	three conventional N-linked glycosylation sites	1234:1280	three conventional N-linked glycosylation sites	1234:1280	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	7	74	theme	glycosylation	1262:1274	arg1	sites					1276:1280	three conventional N-linked glycosylation sites	1234:1280	three conventional N-linked glycosylation sites	1234:1280	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	8	75	theme	atypical	1590:1597	arg1	site					1613:1616	the atypical glycosylation site	1586:1616	the atypical glycosylation site	1586:1616	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	0	76	theme	NK	99:100	arg1	Receptor					102:109	the Activating NK Receptor NKp80	84:115	the Activating NK Receptor NKp80	84:115	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	9	77	from	expression	1791:1800	arg1	cells					1824:1828	calnexin-deficient cells	1805:1828	calnexin-deficient cells	1805:1828	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	4	78	theme	AICL	750:753	arg1	glycoproteins					755:767	AICL glycoproteins	750:767	AICL glycoproteins	750:767	In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression.
29980609	1	79	theme	cytokine	367:374	arg1	secretion					376:384	cytokine secretion	367:384	cytokine secretion	367:384	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	9	80	theme	Stringent	1642:1650	arg1	control					1652:1658	Stringent control	1642:1658	Stringent control of AICL surface expression by glycosylation	1642:1702	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	9	81	from	interaction	1735:1745	arg1	cells					1824:1828	calnexin-deficient cells	1805:1828	calnexin-deficient cells	1805:1828	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	2	82	theme	NK	493:494	arg1	cells					496:500	human NK cells	487:500	human NK cells	487:500	Notably, AICL and NKp80 are encoded by adjacent genes in the NK gene complex and are coexpressed by human NK cells.
29980609	8	83	theme	AICL	1626:1629	arg1	surfacing					1631:1639	AICL surfacing	1626:1639	AICL surfacing	1626:1639	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	8	84	link	N-linked	1511:1518	arg1	glycosylation					1520:1532	conventional N-linked glycosylation	1498:1532	conventional N-linked glycosylation	1498:1532	However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing.
29980609	9	85	theme	calnexin-deficient	1805:1822	arg1	cells					1824:1828	calnexin-deficient cells	1805:1828	calnexin-deficient cells	1805:1828	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	9	86	theme	pronounced	1724:1733	arg1	interaction					1735:1745	the pronounced interaction	1720:1745	the pronounced interaction of AICL with calnexin	1720:1767	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	9	87	theme	surface	1668:1674	arg1	expression					1676:1685	AICL surface expression	1663:1685	AICL surface expression	1663:1685	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	7	88	theme	AICL	1366:1369	arg1	surfacing					1353:1361	surfacing	1353:1361	surfacing	1353:1361	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	7	88	theme	AICL	1366:1369	arg1	maturation					1338:1347	maturation	1338:1347	maturation	1338:1347	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	2	89	theme	adjacent	426:433	arg1	genes					435:439	adjacent genes	426:439	adjacent genes in the NK gene complex	426:462	Notably, AICL and NKp80 are encoded by adjacent genes in the NK gene complex and are coexpressed by human NK cells.
29980609	3	90	theme	AICL	626:629	arg1	surfacing					631:639	AICL surfacing	626:639	AICL surfacing	626:639	Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide.
29980609	7	91	gly	glycosylation	1262:1274	arg2	sites					1276:1280	three conventional N-linked glycosylation sites	1234:1280	three conventional N-linked glycosylation sites	1234:1280	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	7	91	gly	glycosylation	1262:1274	arg2	three					1234:1238	three	1234:1238	three	1234:1238	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	0	92	theme	AICL	45:48	arg1	Glycoproteins					50:62	AICL Glycoproteins	45:62	AICL Glycoproteins	45:62	Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80.
29980609	5	93	theme	surface	1033:1039	arg1	expression					1041:1050	efficient cell surface expression	1018:1050	efficient cell surface expression of AICL homodimers	1018:1069	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	1	94	theme	NK	315:316	arg1	functions					332:340	NK cell effector functions	315:340	NK cell effector functions such as cytotoxicity and cytokine secretion	315:384	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	94	theme	NK	315:316	arg1	cytotoxicity					350:361	cytotoxicity	350:361	cytotoxicity	350:361	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	94	theme	NK	315:316	arg1	secretion					376:384	cytokine secretion	367:384	cytokine secretion	367:384	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	2	95	theme	NK	448:449	arg1	complex					456:462	the NK gene complex	444:462	the NK gene complex	444:462	Notably, AICL and NKp80 are encoded by adjacent genes in the NK gene complex and are coexpressed by human NK cells.
29980609	4	96	theme	surface	830:836	arg1	expression					838:847	AICL surface expression	825:847	AICL surface expression	825:847	In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression.
29980609	1	97	theme	effector	323:330	arg1	functions					332:340	NK cell effector functions	315:340	NK cell effector functions such as cytotoxicity and cytokine secretion	315:384	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	97	theme	effector	323:330	arg1	cytotoxicity					350:361	cytotoxicity	350:361	cytotoxicity	350:361	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	1	97	theme	effector	323:330	arg1	secretion					376:384	cytokine secretion	367:384	cytokine secretion	367:384	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29980609	4	98	theme	intracellular	780:792	arg1	retention					794:802	intracellular retention	780:802	intracellular retention	780:802	In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression.
29980609	5	99	theme	efficient	1018:1026	arg1	expression					1041:1050	efficient cell surface expression	1018:1050	efficient cell surface expression of AICL homodimers	1018:1069	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	7	100	theme	lectin-like	1301:1311	arg1	domain					1313:1318	the AICL C-type lectin-like domain	1285:1318	the AICL C-type lectin-like domain	1285:1318	One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site.
29980609	9	101	with	interaction	1735:1745	arg1	calnexin					1760:1767	calnexin	1760:1767	calnexin	1760:1767	Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells.
29980609	5	102	dep	Cys87	850:854	arg1	only					906:909	only	906:909	only	906:909	Cys87 residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys87 is also required for efficient cell surface expression of AICL homodimers and essential for AICL-NKp80 interaction.
29980609	1	103	theme	all	250:252	arg1	cells					270:274	virtually all mature human NK cells	240:274	virtually all mature human NK cells	240:274	AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80-AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion.
29755357	2	0	from	alterations	419:429	arg1	microbiota					438:447	the microbiota	434:447	the microbiota	434:447	In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.
29755357	1	1	theme	secreted	124:131	arg1	Lipocalin					83:91	Lipocalin 2	83:93	Lipocalin 2 (LCN2)	83:100	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	1	1	theme	secreted	124:131	arg1	adipokine					133:141	a highly conserved secreted adipokine	105:141	a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids	105:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	1	2	theme	fatty	219:223	arg1	acids					225:229	fatty acids	219:229	fatty acids	219:229	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	0	3	theme	Exosome	64:70	arg1	Targeting					72:80	Exosome Targeting	64:80	Exosome Targeting	64:80	N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting.
29755357	6	4	theme	non-glycosylated	1066:1081	arg1	variants					1088:1095	the non-glycosylated LCN2 variants	1062:1095	the non-glycosylated LCN2 variants	1062:1095	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	5	5	dep	line	973:976	arg1	A549					978:981	A549	978:981	human lung carcinoma cell line A549	947:981	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	8	6	from	recruitment	1552:1562	arg1	types					1582:1586	different cell types	1567:1586	different cell types	1567:1586	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	8	7	theme	different	1567:1575	arg1	types					1582:1586	different cell types	1567:1586	different cell types	1567:1586	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	6	8	theme	membranous	1246:1255	arg1	vesicles					1271:1278	these membranous extracellular vesicles	1240:1278	these membranous extracellular vesicles	1240:1278	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	8	9	theme	LCN2	1492:1495	arg1	relevant					1602:1609	relevant	1602:1609	relevant	1602:1609	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	8	9	theme	LCN2	1492:1495	arg1	N-glycosylation					1473:1487	the N-glycosylation	1469:1487	the N-glycosylation of LCN2	1469:1495	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	5	10	theme	cell	968:971	arg1	line					973:976	human lung carcinoma cell line	947:976	human lung carcinoma cell line A549	947:981	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	7	11	gly	N-glycosylation	1343:1357	arg2	embedded					1367:1374	embedded	1367:1374	embedded	1367:1374	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	7	11	gly	N-glycosylation	1343:1357	arg2	site					1359:1362	the N-glycosylation site	1339:1362	the N-glycosylation site	1339:1362	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	5	12	theme	human	988:992	arg1	line					1015:1018	human prostate cancer cell line	988:1018	human prostate cancer cell line PC-3	988:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	13	theme	prostate	994:1001	arg1	line					1015:1018	human prostate cancer cell line	988:1018	human prostate cancer cell line PC-3	988:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	4	14	from	apparatus	694:702	arg1	trafficking					667:677	proper trafficking	660:677	proper trafficking from the Golgi apparatus to the cell surface	660:722	It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion.
29755357	4	15	theme	Golgi	688:692	arg1	apparatus					694:702	the Golgi apparatus	684:702	the Golgi apparatus	684:702	It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion.
29755357	8	16	from	secretion	1524:1532	arg1	types					1582:1586	different cell types	1567:1586	different cell types	1567:1586	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	8	17	gly	N-glycosylation	1473:1487	arg1	LCN2					1492:1495	LCN2	1492:1495	LCN2	1492:1495	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	5	18	theme	cancer	1003:1008	arg1	line					1015:1018	human prostate cancer cell line	988:1018	human prostate cancer cell line PC-3	988:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	7	19	from	surrounding	1425:1435	arg1	embedded					1367:1374	embedded	1367:1374	embedded	1367:1374	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	7	19	from	surrounding	1425:1435	arg1	site					1359:1362	the N-glycosylation site	1339:1362	the N-glycosylation site	1339:1362	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	3	20	theme	Human	450:454	arg1	LCN2					456:459	Human LCN2	450:459	Human LCN2	450:459	Human LCN2 contains one N-glycosylation site conserved in other species.
29755357	4	21	theme	effective	751:759	arg1	secretion					761:769	effective secretion	751:769	effective secretion	751:769	It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion.
29755357	5	22	theme	primary	898:904	arg1	hepatocytes					913:923	primary murine hepatocytes	898:923	primary murine hepatocytes	898:923	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	8	23	theme	cell	1577:1580	arg1	types					1582:1586	different cell types	1567:1586	different cell types	1567:1586	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	8	24	theme	exosome	1538:1544	arg1	recruitment					1552:1562	exosome cargo recruitment	1538:1562	exosome cargo recruitment	1538:1562	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	2	25	theme	bacterial	270:278	arg1	growth					280:285	bacterial growth	270:285	bacterial growth	270:285	In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.
29755357	2	26	theme	intestinal	361:370	arg1	inflammation					372:383	inflammation	372:383	inflammation	372:383	In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.
29755357	5	27	theme	N-linked	846:853	arg1	glycosylation					855:867	N-linked glycosylation	846:867	N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3	846:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	7	28	theme	conserved	1415:1423	arg1	surrounding					1425:1435	a highly hydrophobic evolutionarily conserved surrounding	1379:1435	a highly hydrophobic evolutionarily conserved surrounding	1379:1435	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	3	29	gly	N-glycosylation	474:488	arg2	site					490:493	one N-glycosylation site	470:493	one N-glycosylation site conserved in other species	470:520	Human LCN2 contains one N-glycosylation site conserved in other species.
29755357	3	29	gly	N-glycosylation	474:488	arg2	one					470:472	one	470:472	one	470:472	Human LCN2 contains one N-glycosylation site conserved in other species.
29755357	1	30	theme	transport	161:169	arg1	protein					171:177	a serum transport protein	153:177	a serum transport protein for small hydrophobic molecules such as fatty acids and steroids	153:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	0	31	theme	Lipocalin	19:27	arg1	N-Glycosylation					0:14	N-Glycosylation	0:14	N-Glycosylation of Lipocalin 2	0:29	N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting.
29755357	4	32	theme	protein	600:606	arg1	folding					608:614	protein folding	600:614	protein folding	600:614	It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion.
29755357	6	33	gly	non-glycosylated	1066:1081	arg1	variants					1088:1095	the non-glycosylated LCN2 variants	1062:1095	the non-glycosylated LCN2 variants	1062:1095	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	3	34	contain	contains	461:468	arg2	site					490:493	one N-glycosylation site	470:493	one N-glycosylation site conserved in other species	470:520	Human LCN2 contains one N-glycosylation site conserved in other species.
29755357	3	34	contain	contains	461:468	arg1	LCN2					456:459	Human LCN2	450:459	Human LCN2	450:459	Human LCN2 contains one N-glycosylation site conserved in other species.
29755357	3	35	theme	N-glycosylation	474:488	arg1	site					490:493	one N-glycosylation site	470:493	one N-glycosylation site conserved in other species	470:520	Human LCN2 contains one N-glycosylation site conserved in other species.
29755357	2	36	theme	iron-containing	303:317	arg1	siderophores					319:330	iron-containing siderophores	303:330	iron-containing siderophores	303:330	In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota.
29755357	7	37	theme	hydrophobic	1296:1306	arg1	analysis					1316:1323	a hydrophobic cluster analysis	1294:1323	a hydrophobic cluster analysis	1294:1323	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	0	38	gly	N-Glycosylation	0:14	arg1	Lipocalin					19:27	Lipocalin 2	19:29	Lipocalin 2	19:29	N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting.
29755357	1	39	theme	serum	155:159	arg1	protein					171:177	a serum transport protein	153:177	a serum transport protein for small hydrophobic molecules such as fatty acids and steroids	153:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	7	40	theme	N-glycosylation	1343:1357	arg1	embedded					1367:1374	embedded	1367:1374	embedded	1367:1374	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	7	40	theme	N-glycosylation	1343:1357	arg1	site					1359:1362	the N-glycosylation site	1339:1362	the N-glycosylation site	1339:1362	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	5	41	theme	LCN2	890:893	arg1	secretion					877:885	secretion	877:885	N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3	846:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	42	theme	homologous	794:803	arg1	tunicamycin					827:837	the homologous nucleoside antibiotic tunicamycin	790:837	the homologous nucleoside antibiotic tunicamycin	790:837	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	8	43	theme	proper	1517:1522	arg1	secretion					1524:1532	proper secretion	1517:1532	proper secretion	1517:1532	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	5	44	theme	human	947:951	arg1	line					973:976	human lung carcinoma cell line	947:976	human lung carcinoma cell line A549	947:981	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	45	from	secretion	877:885	arg1	derivatives					926:936	derivatives	926:936	derivatives thereof	926:944	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	45	from	secretion	877:885	arg1	hepatocytes					913:923	primary murine hepatocytes	898:923	primary murine hepatocytes	898:923	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	45	from	secretion	877:885	arg1	line					1015:1018	human prostate cancer cell line	988:1018	human prostate cancer cell line PC-3	988:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	45	from	secretion	877:885	arg1	line					973:976	human lung carcinoma cell line	947:976	human lung carcinoma cell line A549	947:981	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	1	46	theme	small	183:187	arg1	acids					225:229	fatty acids	219:229	fatty acids	219:229	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	1	46	theme	small	183:187	arg1	molecules					201:209	small hydrophobic molecules	183:209	small hydrophobic molecules such as fatty acids and steroids	183:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	1	46	theme	small	183:187	arg1	steroids					235:242	steroids	235:242	steroids	235:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	5	47	theme	nucleoside	805:814	arg1	tunicamycin					827:837	the homologous nucleoside antibiotic tunicamycin	790:837	the homologous nucleoside antibiotic tunicamycin	790:837	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	8	48	theme	overall	1623:1629	arg1	solubility					1631:1640	overall solubility	1623:1640	overall solubility	1623:1640	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	6	49	theme	post-translational	1155:1172	arg1	modification					1174:1185	this post-translational modification	1150:1185	this post-translational modification	1150:1185	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	5	50	theme	antibiotic	816:825	arg1	tunicamycin					827:837	the homologous nucleoside antibiotic tunicamycin	790:837	the homologous nucleoside antibiotic tunicamycin	790:837	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	4	51	theme	post-translational	551:568	arg1	modification					570:581	this post-translational modification	546:581	this post-translational modification	546:581	It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion.
29755357	6	52	theme	extracellular	1257:1269	arg1	vesicles					1271:1278	these membranous extracellular vesicles	1240:1278	these membranous extracellular vesicles	1240:1278	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	7	53	theme	hydrophobic	1388:1398	arg1	surrounding					1425:1435	a highly hydrophobic evolutionarily conserved surrounding	1379:1435	a highly hydrophobic evolutionarily conserved surrounding	1379:1435	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	3	54	theme	other	508:512	arg1	species					514:520	other species	508:520	other species	508:520	Human LCN2 contains one N-glycosylation site conserved in other species.
29755357	7	55	theme	cluster	1308:1314	arg1	analysis					1316:1323	a hydrophobic cluster analysis	1294:1323	a hydrophobic cluster analysis	1294:1323	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	5	56	theme	cell	1010:1013	arg1	line					1015:1018	human prostate cancer cell line	988:1018	human prostate cancer cell line PC-3	988:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	57	link	N-linked	846:853	arg1	glycosylation					855:867	N-linked glycosylation	846:867	N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3	846:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	7	58	from	embedded	1367:1374	arg1	surrounding					1425:1435	a highly hydrophobic evolutionarily conserved surrounding	1379:1435	a highly hydrophobic evolutionarily conserved surrounding	1379:1435	Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding.
29755357	5	59	theme	lung	953:956	arg1	line					973:976	human lung carcinoma cell line	947:976	human lung carcinoma cell line A549	947:981	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	60	theme	murine	906:911	arg1	hepatocytes					913:923	primary murine hepatocytes	898:923	primary murine hepatocytes	898:923	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	1	61	theme	hydrophobic	189:199	arg1	acids					225:229	fatty acids	219:229	fatty acids	219:229	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	1	61	theme	hydrophobic	189:199	arg1	molecules					201:209	small hydrophobic molecules	183:209	small hydrophobic molecules such as fatty acids and steroids	183:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	1	61	theme	hydrophobic	189:199	arg1	steroids					235:242	steroids	235:242	steroids	235:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	8	62	theme	cargo	1546:1550	arg1	recruitment					1552:1562	exosome cargo recruitment	1538:1562	exosome cargo recruitment	1538:1562	In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.
29755357	6	63	theme	LCN2	1083:1086	arg1	variants					1088:1095	the non-glycosylated LCN2 variants	1062:1095	the non-glycosylated LCN2 variants	1062:1095	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	5	64	theme	carcinoma	958:966	arg1	line					973:976	human lung carcinoma cell line	947:976	human lung carcinoma cell line A549	947:981	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	5	65	dep	line	1015:1018	arg1	PC-3					1020:1023	PC-3	1020:1023	human prostate cancer cell line PC-3	988:1023	We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3.
29755357	4	66	theme	proper	660:665	arg1	trafficking					667:677	proper trafficking	660:677	proper trafficking from the Golgi apparatus to the cell surface	660:722	It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion.
29755357	4	67	theme	cell	711:714	arg1	surface					716:722	the cell surface	707:722	the cell surface	707:722	It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion.
29755357	6	68	theme	proper	1208:1213	arg1	trafficking					1215:1225	proper trafficking	1208:1225	proper trafficking of LCN2 into these membranous extracellular vesicles	1208:1278	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	6	69	theme	LCN2	1230:1233	arg1	trafficking					1215:1225	proper trafficking	1208:1225	proper trafficking of LCN2 into these membranous extracellular vesicles	1208:1278	Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles.
29755357	1	70	theme	conserved	114:122	arg1	Lipocalin					83:91	Lipocalin 2	83:93	Lipocalin 2 (LCN2)	83:100	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
29755357	1	70	theme	conserved	114:122	arg1	adipokine					133:141	a highly conserved secreted adipokine	105:141	a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids	105:242	Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids.
30190529	3	0	theme	vaccinated	611:620	arg1	communities					622:632	vaccinated communities	611:632	vaccinated communities	611:632	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	1	theme	recent	591:596	arg1	outbreaks					598:606	recent outbreaks	591:606	recent outbreaks in vaccinated communities	591:632	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	1	2	from	targets	274:280	arg1	pathogenesis					243:254	mumps pathogenesis	237:254	mumps pathogenesis	237:254	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	4	3	theme	G	772:772	arg1	strains					774:780	genotype G strains	763:780	genotype G strains	763:780	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	1	4	theme	key	222:224	arg1	factors					226:232	key factors	222:232	key factors in mumps pathogenesis	222:254	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	4	theme	key	222:224	arg1	proteins					127:134	The surface proteins	115:134	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN),	115:216	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	7	5	theme	virus	1265:1269	arg1	pathogenesis					1271:1282	mumps virus pathogenesis	1259:1282	mumps virus pathogenesis	1259:1282	We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis.
30190529	2	6	theme	G	499:499	arg1	strains					501:507	mumps virus genotype G strains	478:507	mumps virus genotype G strains (from 2004 onwards)	478:527	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	6	7	theme	genotype	1124:1131	arg1	strains					1135:1141	genotype G strains	1124:1141	genotype G strains	1124:1141	These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains.
30190529	1	8	theme	fusion	160:165	arg1	virus					149:153	the mumps virus	139:153	the mumps virus	139:153	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	8	theme	fusion	160:165	arg1	F					176:176	F	176:176	F	176:176	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	8	theme	fusion	160:165	arg1	protein					167:173	the fusion protein	156:173	the fusion protein (F)	156:177	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	4	9	theme	known	812:816	arg1	epitopes					825:832	known B-cell epitopes	812:832	known B-cell epitopes	812:832	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	3	10	theme	Western	649:655	arg1	Europe					657:662	Western Europe	649:662	Western Europe	649:662	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	5	11	theme	A	957:957	arg1	sequences					973:981	genotype A or genotype G sequences	948:981	genotype A or genotype G sequences in five known B-cell epitopes of the HN protein	948:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	4	12	located	located	801:807	arg2	differences					695:705	Amino acid differences	684:705	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains	684:780	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	4	12	located	located	801:807	arg1	epitopes					825:832	known B-cell epitopes	812:832	known B-cell epitopes	812:832	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	3	13	from	outbreaks	598:606	arg1	communities					622:632	vaccinated communities	611:632	vaccinated communities	611:632	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	5	14	theme	genotype	962:969	arg1	G					971:971	genotype G	962:971	genotype G	962:971	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	2	15	from	samples	428:434	arg1	sequences					373:381	the predicted amino acid sequences	348:381	the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982)	348:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	4	16	from	located	801:807	arg1	epitopes					825:832	known B-cell epitopes	812:832	known B-cell epitopes	812:832	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	2	17	theme	genotype	490:497	arg1	strains					501:507	mumps virus genotype G strains	478:507	mumps virus genotype G strains (from 2004 onwards)	478:527	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	1	18	theme	surface	119:125	arg1	factors					226:232	key factors	222:232	key factors in mumps pathogenesis	222:254	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	18	theme	surface	119:125	arg1	proteins					127:134	The surface proteins	115:134	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN),	115:216	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	2	19	from	era	457:459	arg1	samples					428:434	Dutch mumps virus samples	410:434	Dutch mumps virus samples from the pre-vaccine era (1957-1982)	410:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	7	20	theme	HN	1206:1207	arg1	protein					1209:1215	the HN protein	1202:1215	the HN protein	1202:1215	We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis.
30190529	5	21	theme	B-cell	997:1002	arg1	epitopes					1004:1011	five known B-cell epitopes	986:1011	five known B-cell epitopes of the HN protein	986:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	2	22	theme	virus	422:426	arg1	samples					428:434	Dutch mumps virus samples	410:434	Dutch mumps virus samples from the pre-vaccine era (1957-1982)	410:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	8	23	theme	G	1348:1348	arg1	outbreaks					1350:1358	genotype G outbreaks	1339:1358	genotype G outbreaks	1339:1358	These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities.
30190529	1	24	theme	immune	290:295	arg1	response					297:304	the immune response	286:304	the immune response during mumps virus infection	286:333	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	25	theme	mumps	143:147	arg1	virus					149:153	the mumps virus	139:153	the mumps virus	139:153	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	25	theme	mumps	143:147	arg1	haemagglutinin-neuraminidase					183:210	haemagglutinin-neuraminidase	183:210	haemagglutinin-neuraminidase (HN)	183:215	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	25	theme	mumps	143:147	arg1	protein					167:173	the fusion protein	156:173	the fusion protein (F)	156:177	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	0	26	from	Differences	0:10	arg1	sites					25:29	antigenic sites	15:29	antigenic sites	15:29	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	0	26	from	Differences	0:10	arg1	regions					52:58	other functional regions	35:58	other functional regions	35:58	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	0	27	theme	G	83:83	arg1	proteins					105:112	G mumps virus surface proteins	83:112	G mumps virus surface proteins	83:112	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	2	28	theme	pre-vaccine	445:455	arg1	1957-1982					462:470	1957-1982	462:470	1957-1982	462:470	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	2	28	theme	pre-vaccine	445:455	arg1	era					457:459	the pre-vaccine era	441:459	the pre-vaccine era (1957-1982)	441:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	0	29	theme	virus	91:95	arg1	proteins					105:112	G mumps virus surface proteins	83:112	G mumps virus surface proteins	83:112	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	1	30	theme	virus	319:323	arg1	infection					325:333	mumps virus infection	313:333	mumps virus infection	313:333	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	6	31	theme	reported	1070:1077	arg1	differences					1089:1099	the reported antigenic differences	1066:1099	the reported antigenic differences between Jeryl Lynn and genotype G strains	1066:1141	These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains.
30190529	0	32	theme	antigenic	15:23	arg1	sites					25:29	antigenic sites	15:29	antigenic sites	15:29	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	1	33	theme	mumps	237:241	arg1	pathogenesis					243:254	mumps pathogenesis	237:254	mumps pathogenesis	237:254	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	4	34	gly	glycosylation	850:862	arg2	sites					864:868	N-linked glycosylation sites	841:868	N-linked glycosylation sites on the HN protein	841:886	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	2	35	theme	Dutch	410:414	arg1	samples					428:434	Dutch mumps virus samples	410:434	Dutch mumps virus samples from the pre-vaccine era (1957-1982)	410:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	4	36	theme	Jeryl	719:723	arg1	strains					738:744	the Jeryl Lynn vaccine strains	715:744	the Jeryl Lynn vaccine strains (genotype A)	715:757	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	4	36	theme	Jeryl	719:723	arg1	A					756:756	genotype A	747:756	genotype A	747:756	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	2	37	theme	amino	362:366	arg1	sequences					373:381	the predicted amino acid sequences	348:381	the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982)	348:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	5	38	theme	HN	1020:1021	arg1	protein					1023:1029	the HN protein	1016:1029	the HN protein	1016:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	5	39	theme	variable	906:913	arg1	positions					926:934	eight variable amino acid positions	900:934	eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein	900:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	2	40	theme	genes	399:403	arg1	sequences					373:381	the predicted amino acid sequences	348:381	the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982)	348:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	4	41	theme	vaccine	730:736	arg1	strains					738:744	the Jeryl Lynn vaccine strains	715:744	the Jeryl Lynn vaccine strains (genotype A)	715:757	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	4	41	theme	vaccine	730:736	arg1	A					756:756	genotype A	747:756	genotype A	747:756	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	0	42	theme	functional	41:50	arg1	regions					52:58	other functional regions	35:58	other functional regions	35:58	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	1	43	theme	important	264:272	arg1	targets					274:280	important targets	264:280	important targets for the immune response during mumps virus infection	264:333	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	5	44	theme	acid	921:924	arg1	positions					926:934	eight variable amino acid positions	900:934	eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein	900:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	7	45	theme	amino	1158:1162	arg1	differences					1169:1179	amino acid differences	1158:1179	amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis	1158:1282	We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis.
30190529	4	46	theme	acid	690:693	arg1	differences					695:705	Amino acid differences	684:705	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains	684:780	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	3	47	theme	mumps	573:577	arg1	genotype					579:586	the most frequently detected mumps genotype	544:586	the most frequently detected mumps genotype in recent outbreaks in vaccinated communities	544:632	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	47	theme	mumps	573:577	arg1	G					539:539	Genotype G	530:539	Genotype G	530:539	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	48	from	genotype	579:586	arg1	Japan					677:681	Japan	677:681	Japan	677:681	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	48	from	genotype	579:586	arg1	Europe					657:662	Western Europe	649:662	Western Europe	649:662	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	48	from	genotype	579:586	arg1	USA					669:671	the USA	665:671	the USA	665:671	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	48	from	genotype	579:586	arg1	outbreaks					598:606	recent outbreaks	591:606	recent outbreaks in vaccinated communities	591:632	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	4	49	theme	HN	877:878	arg1	protein					880:886	the HN protein	873:886	the HN protein	873:886	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	6	50	theme	G	1133:1133	arg1	strains					1135:1141	genotype G strains	1124:1141	genotype G strains	1124:1141	These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains.
30190529	8	51	from	occurrence	1325:1334	arg1	communities					1374:1384	vaccinated communities	1363:1384	vaccinated communities	1363:1384	These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities.
30190529	4	52	theme	genotype	763:770	arg1	strains					774:780	genotype G strains	763:780	genotype G strains	763:780	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	1	53	theme	virus	149:153	arg1	factors					226:232	key factors	222:232	key factors in mumps pathogenesis	222:254	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	53	theme	virus	149:153	arg1	proteins					127:134	The surface proteins	115:134	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN),	115:216	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	1	54	from	factors	226:232	arg1	pathogenesis					243:254	mumps pathogenesis	237:254	mumps pathogenesis	237:254	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	4	55	theme	genotype	747:754	arg1	strains					738:744	the Jeryl Lynn vaccine strains	715:744	the Jeryl Lynn vaccine strains (genotype A)	715:757	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	4	55	theme	genotype	747:754	arg1	A					756:756	genotype A	747:756	genotype A	747:756	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	7	56	theme	mumps	1259:1263	arg1	virus					1265:1269	mumps virus	1259:1269	mumps virus pathogenesis	1259:1282	We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis.
30190529	4	57	theme	B-cell	818:823	arg1	epitopes					825:832	known B-cell epitopes	812:832	known B-cell epitopes	812:832	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	5	58	theme	G	971:971	arg1	sequences					973:981	genotype A or genotype G sequences	948:981	genotype A or genotype G sequences in five known B-cell epitopes of the HN protein	948:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	2	59	theme	mumps	478:482	arg1	strains					501:507	mumps virus genotype G strains	478:507	mumps virus genotype G strains (from 2004 onwards)	478:527	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	5	60	theme	specific	936:943	arg1	positions					926:934	eight variable amino acid positions	900:934	eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein	900:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	3	61	theme	Genotype	530:537	arg1	genotype					579:586	the most frequently detected mumps genotype	544:586	the most frequently detected mumps genotype in recent outbreaks in vaccinated communities	544:632	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	61	theme	Genotype	530:537	arg1	G					539:539	Genotype G	530:539	Genotype G	530:539	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	2	62	theme	virus	484:488	arg1	strains					501:507	mumps virus genotype G strains	478:507	mumps virus genotype G strains (from 2004 onwards)	478:527	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	8	63	theme	genotype	1339:1346	arg1	outbreaks					1350:1358	genotype G outbreaks	1339:1358	genotype G outbreaks	1339:1358	These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities.
30190529	6	64	theme	antigenic	1079:1087	arg1	differences					1089:1099	the reported antigenic differences	1066:1099	the reported antigenic differences between Jeryl Lynn and genotype G strains	1066:1141	These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains.
30190529	0	65	theme	genotype	68:75	arg1	A					77:77	genotype A	68:77	genotype A	68:77	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	5	66	theme	genotype	948:955	arg1	A					957:957	genotype A	948:957	genotype A	948:957	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	8	67	theme	outbreaks	1350:1358	arg1	occurrence					1325:1334	the occurrence	1321:1334	the occurrence of genotype G outbreaks in vaccinated communities	1321:1384	These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities.
30190529	2	68	theme	mumps	416:420	arg1	samples					428:434	Dutch mumps virus samples	410:434	Dutch mumps virus samples from the pre-vaccine era (1957-1982)	410:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	8	69	theme	vaccinated	1363:1372	arg1	communities					1374:1384	vaccinated communities	1363:1384	vaccinated communities	1363:1384	These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities.
30190529	4	70	from	epitopes	825:832	arg1	located					801:807	located	801:807	located	801:807	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	0	71	theme	mumps	85:89	arg1	proteins					105:112	G mumps virus surface proteins	83:112	G mumps virus surface proteins	83:112	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	0	72	theme	surface	97:103	arg1	proteins					105:112	G mumps virus surface proteins	83:112	G mumps virus surface proteins	83:112	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	1	73	theme	mumps	313:317	arg1	virus					319:323	mumps virus	313:323	mumps virus infection	313:333	The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection.
30190529	4	74	theme	N-linked	841:848	arg1	sites					864:868	N-linked glycosylation sites	841:868	N-linked glycosylation sites on the HN protein	841:886	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	4	75	theme	glycosylation	850:862	arg1	sites					864:868	N-linked glycosylation sites	841:868	N-linked glycosylation sites on the HN protein	841:886	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	5	76	theme	known	991:995	arg1	epitopes					1004:1011	five known B-cell epitopes	986:1011	five known B-cell epitopes of the HN protein	986:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	2	77	theme	F	390:390	arg1	genes					399:403	the F and HN genes	386:403	genes	399:403	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	5	78	from	sequences	973:981	arg1	epitopes					1004:1011	five known B-cell epitopes	986:1011	five known B-cell epitopes of the HN protein	986:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	2	79	from	onwards	520:526	arg1	strains					501:507	mumps virus genotype G strains	478:507	mumps virus genotype G strains (from 2004 onwards)	478:527	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	2	80	theme	acid	368:371	arg1	sequences					373:381	the predicted amino acid sequences	348:381	the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982)	348:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	0	81	theme	other	35:39	arg1	regions					52:58	other functional regions	35:58	other functional regions	35:58	Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins.
30190529	7	82	theme	acid	1164:1167	arg1	differences					1169:1179	amino acid differences	1158:1179	amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis	1158:1282	We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis.
30190529	2	83	theme	predicted	352:360	arg1	sequences					373:381	the predicted amino acid sequences	348:381	the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982)	348:471	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	5	84	theme	protein	1023:1029	arg1	epitopes					1004:1011	five known B-cell epitopes	986:1011	five known B-cell epitopes of the HN protein	986:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	5	85	theme	amino	915:919	arg1	positions					926:934	eight variable amino acid positions	900:934	eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein	900:1029	There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein.
30190529	2	86	theme	HN	396:397	arg1	genes					399:403	the F and HN genes	386:403	genes	399:403	We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards).
30190529	4	87	link	N-linked	841:848	arg1	sites					864:868	N-linked glycosylation sites	841:868	N-linked glycosylation sites on the HN protein	841:886	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	4	88	theme	Lynn	725:728	arg1	strains					738:744	the Jeryl Lynn vaccine strains	715:744	the Jeryl Lynn vaccine strains (genotype A)	715:757	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	4	88	theme	Lynn	725:728	arg1	A					756:756	genotype A	747:756	genotype A	747:756	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	3	89	theme	detected	564:571	arg1	genotype					579:586	the most frequently detected mumps genotype	544:586	the most frequently detected mumps genotype in recent outbreaks in vaccinated communities	544:632	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	3	89	theme	detected	564:571	arg1	G					539:539	Genotype G	530:539	Genotype G	530:539	Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan.
30190529	4	90	theme	Amino	684:688	arg1	differences					695:705	Amino acid differences	684:705	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains	684:780	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30190529	7	91	from	sites	1193:1197	arg1	protein					1209:1215	the HN protein	1202:1215	the HN protein	1202:1215	We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis.
30190529	4	92	from	sites	864:868	arg1	protein					880:886	the HN protein	873:886	the HN protein	873:886	Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein.
30205382	1	0	theme	retinal	357:363	arg1	RVECs					393:397	RVECs	393:397	RVECs	393:397	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	0	theme	retinal	357:363	arg1	cells					386:390	primary retinal vascular endothelial cells	349:390	primary retinal vascular endothelial cells (RVECs)	349:398	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	1	from	expression	335:344	arg1	RVECs					393:397	RVECs	393:397	RVECs	393:397	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	1	from	expression	335:344	arg1	cells					386:390	primary retinal vascular endothelial cells	349:390	primary retinal vascular endothelial cells (RVECs)	349:398	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	2	theme	transducer	274:283	arg1	increase					195:202	an increase	192:202	an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	192:260	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	2	theme	transducer	274:283	arg1	expression					335:344	and signal transducer and activator of transcription proteins 3 (STAT3) expression	263:344	and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs)	263:398	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	2	3	theme	STAT3	554:558	arg1	phosphorylation					560:574	STAT3 phosphorylation	554:574	STAT3 phosphorylation	554:574	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	1	4	theme	vascular	365:372	arg1	RVECs					393:397	RVECs	393:397	RVECs	393:397	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	4	theme	vascular	365:372	arg1	cells					386:390	primary retinal vascular endothelial cells	349:390	primary retinal vascular endothelial cells (RVECs)	349:398	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	5	theme	diabetic	453:460	arg1	DR					475:476	DR	475:476	DR	475:476	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	5	theme	diabetic	453:460	arg1	retinopathy					462:472	diabetic retinopathy	453:472	diabetic retinopathy (DR)	453:477	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	10	6	theme	DR	1875:1876	arg1	mechanisms					1861:1870	the mechanisms	1857:1870	the mechanisms of DR and other diabetic complications	1857:1909	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	10	7	theme	RVECs	1720:1724	arg1	apoptosis					1726:1734	RVECs apoptosis	1720:1734	RVECs apoptosis	1720:1734	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	4	8	theme	involved	909:916	arg1	expression					926:935	involved protein expression	909:935	involved protein expression	909:935	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	0	9	from	Identification	0:13	arg1	Retinopathy					59:69	Diabetic Retinopathy	50:69	Diabetic Retinopathy	50:69	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	5	10	theme	O-GlcNAcylation	1004:1018	arg1	levels					1031:1036	Global O-GlcNAcylation and pSTAT3 levels	997:1036	Global O-GlcNAcylation and pSTAT3 levels	997:1036	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	1	11	theme	activator	289:297	arg1	increase					195:202	an increase	192:202	an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	192:260	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	11	theme	activator	289:297	arg1	expression					335:344	and signal transducer and activator of transcription proteins 3 (STAT3) expression	263:344	and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs)	263:398	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	0	12	theme	STAT3	109:113	arg1	Phosphorylation					90:104	Phosphorylation	90:104	Phosphorylation of STAT3 in Retina Vascular Endothelium Cells	90:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	4	13	theme	protein	918:924	arg1	expression					926:935	involved protein expression	909:935	involved protein expression	909:935	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	2	14	theme	O-GlcNAcylation	648:662	arg1	Expression					634:643	Expression	634:643	regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3	610:672	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	7	15	theme	augmented	1273:1281	arg1	O-GlcNAcylation					1283:1297	augmented O-GlcNAcylation	1273:1297	augmented O-GlcNAcylation	1273:1297	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	0	16	theme	Vascular	125:132	arg1	Cells					146:150	Retina Vascular Endothelium Cells	118:150	Retina Vascular Endothelium Cells	118:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	0	17	from	Retinopathy	59:69	arg1	Identification					0:13	Identification	0:13	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy	0:69	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	0	17	from	Retinopathy	59:69	arg1	Crosstalk					75:83	Crosstalk	75:83	Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells	75:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	4	18	theme	human	884:888	arg1	apoptosis					895:903	human RVEC apoptosis	884:903	human RVEC apoptosis	884:903	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	0	19	with	Crosstalk	75:83	arg1	Phosphorylation					90:104	Phosphorylation	90:104	Phosphorylation of STAT3 in Retina Vascular Endothelium Cells	90:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	5	20	theme	pSTAT3	1024:1029	arg1	levels					1031:1036	Global O-GlcNAcylation and pSTAT3 levels	997:1036	Global O-GlcNAcylation and pSTAT3 levels	997:1036	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	2	21	with	effects	597:603	arg1	regards					610:616	regards	610:616	regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3	610:672	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	6	22	theme	In	1138:1139	arg1	assays					1147:1152	In vitro assays	1138:1152	In vitro assays	1138:1152	In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose.
30205382	0	23	theme	Retina	118:123	arg1	Cells					146:150	Retina Vascular Endothelium Cells	118:150	Retina Vascular Endothelium Cells	118:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	2	24	dep	regards	610:616	arg1	METHODS					625:631	METHODS	625:631	regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3	610:672	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	2	24	dep	regards	610:616	arg1	Expression					634:643	Expression	634:643	regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3	610:672	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	2	25	theme	DR-affected	691:701	arg1	tissues					703:709	DR-affected tissues	691:709	DR-affected tissues	691:709	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	9	26	theme	related	1632:1638	arg1	apoptosis					1622:1630	human RVEC apoptosis	1611:1630	human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway	1611:1675	Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway.
30205382	7	27	theme	p727STAT3	1251:1259	arg1	expression					1261:1270	p727STAT3 expression	1251:1270	p727STAT3 expression	1251:1270	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	7	28	theme	endothelial	1390:1400	arg1	factor					1409:1414	vascular endothelial growth factor	1381:1414	vascular endothelial growth factor (VEGF) changes	1381:1429	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	7	28	theme	endothelial	1390:1400	arg1	VEGF					1417:1420	VEGF	1417:1420	VEGF	1417:1420	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	10	29	theme	STAT3	1803:1807	arg1	phosphorylation					1809:1823	STAT3 phosphorylation	1803:1823	STAT3 phosphorylation	1803:1823	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	1	30	theme	transcription	302:314	arg1	proteins					316:323	transcription proteins 3	302:325	transcription proteins 3	302:325	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	4	31	theme	RVEC	890:893	arg1	apoptosis					895:903	human RVEC apoptosis	884:903	human RVEC apoptosis	884:903	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	6	32	theme	high	1205:1208	arg1	glucose					1210:1216	high glucose	1205:1216	high glucose	1205:1216	In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose.
30205382	1	33	theme	high	406:409	arg1	conditions					419:428	high glucose conditions	406:428	high glucose conditions	406:428	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	0	34	theme	Modification	34:45	arg1	Identification					0:13	Identification	0:13	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy	0:69	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	0	34	theme	Modification	34:45	arg1	Crosstalk					75:83	Crosstalk	75:83	Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells	75:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	1	35	theme	proteins	316:323	arg1	activator					289:297	activator	289:297	activator of transcription proteins 3	289:325	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	35	theme	proteins	316:323	arg1	STAT3					328:332	STAT3	328:332	STAT3	328:332	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	35	theme	proteins	316:323	arg1	transducer					274:283	signal transducer	267:283	signal transducer	267:283	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	6	36	dep	In	1138:1139	arg1	vitro					1141:1145	vitro	1141:1145	vitro	1141:1145	In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose.
30205382	2	37	theme	STAT3	668:672	arg1	Expression					634:643	Expression	634:643	regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3	610:672	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	1	38	theme	O-GlcNAc	207:214	arg1	modification					249:260	O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	207:260	O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	207:260	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	0	39	theme	O-GlcNAcylation	18:32	arg1	Modification					34:45	O-GlcNAcylation Modification	18:45	O-GlcNAcylation Modification in Diabetic Retinopathy	18:69	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	9	40	theme	human	1611:1615	arg1	apoptosis					1622:1630	human RVEC apoptosis	1611:1630	human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway	1611:1675	Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway.
30205382	0	41	theme	Endothelium	134:144	arg1	Cells					146:150	Retina Vascular Endothelium Cells	118:150	Retina Vascular Endothelium Cells	118:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	5	42	theme	glucose	1118:1124	arg1	conditions					1126:1135	high glucose conditions	1113:1135	high glucose conditions	1113:1135	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	5	43	theme	Global	997:1002	arg1	levels					1031:1036	Global O-GlcNAcylation and pSTAT3 levels	997:1036	Global O-GlcNAcylation and pSTAT3 levels	997:1036	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	10	44	theme	new	1839:1841	arg1	insights					1843:1850	new insights	1839:1850	new insights into the mechanisms of DR and other diabetic complications	1839:1909	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	0	45	theme	Diabetic	50:57	arg1	Retinopathy					59:69	Diabetic Retinopathy	50:69	Diabetic Retinopathy	50:69	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	7	46	theme	growth	1402:1407	arg1	factor					1409:1414	vascular endothelial growth factor	1381:1414	vascular endothelial growth factor (VEGF) changes	1381:1429	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	7	46	theme	growth	1402:1407	arg1	VEGF					1417:1420	VEGF	1417:1420	VEGF	1417:1420	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	10	47	from	pathway	1754:1760	arg1	DR					1765:1766	DR	1765:1766	DR	1765:1766	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	0	48	from	Phosphorylation	90:104	arg1	Cells					146:150	Retina Vascular Endothelium Cells	118:150	Retina Vascular Endothelium Cells	118:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	5	49	theme	diabetic	1069:1076	arg1	retina					1082:1087	diabetic rat retina	1069:1087	diabetic rat retina	1069:1087	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	9	50	theme	O-GlcNAcylation	1581:1595	arg1	overexpression					1563:1576	overexpression	1563:1576	overexpression of O-GlcNAcylation	1563:1595	Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway.
30205382	1	51	theme	O-linked-ß-N-acetylglucosamine	217:246	arg1	modification					249:260	O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	207:260	O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	207:260	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	10	52	theme	STAT3	1748:1752	arg1	pathway					1754:1760	the STAT3 pathway	1744:1760	the STAT3 pathway in DR	1744:1766	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	4	53	theme	Western	974:980	arg1	blot					982:985	Western blot	974:985	Western blot	974:985	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	1	54	theme	glucose	411:417	arg1	conditions					419:428	high glucose conditions	406:428	high glucose conditions	406:428	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	5	55	theme	rat	1078:1080	arg1	retina					1082:1087	diabetic rat retina	1069:1087	diabetic rat retina	1069:1087	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	3	56	theme	Western	831:837	arg1	analysis					844:851	Western blot analysis	831:851	Western blot analysis	831:851	The relationship between O-GlcNAcylation and STAT3 was further delineated by immunoprecipitation and Western blot analysis.
30205382	2	57	theme	potential	587:595	arg1	effects					597:603	their potential effects	581:603	their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3	581:672	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	0	58	from	Crosstalk	75:83	arg1	Retinopathy					59:69	Diabetic Retinopathy	50:69	Diabetic Retinopathy	50:69	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	4	59	theme	O-GlcNAcylation	865:879	arg1	Effects					854:860	Effects	854:860	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression	854:935	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	2	60	theme	primary	715:721	arg1	RVECs					723:727	primary RVECs	715:727	primary RVECs	715:727	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	1	61	theme	endothelial	374:384	arg1	RVECs					393:397	RVECs	393:397	RVECs	393:397	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	61	theme	endothelial	374:384	arg1	cells					386:390	primary retinal vascular endothelial cells	349:390	primary retinal vascular endothelial cells (RVECs)	349:398	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	62	theme	primary	349:355	arg1	RVECs					393:397	RVECs	393:397	RVECs	393:397	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	62	theme	primary	349:355	arg1	cells					386:390	primary retinal vascular endothelial cells	349:390	primary retinal vascular endothelial cells (RVECs)	349:398	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	5	63	theme	primary	1093:1099	arg1	RVECs					1101:1105	primary RVECs	1093:1105	primary RVECs	1093:1105	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	8	64	mod	modified	1476:1483	arg3	O-GlcNAcylation					1488:1502	O-GlcNAcylation	1488:1502	O-GlcNAcylation	1488:1502	Immunoprecipitation revealed that STAT3 was modified by O-GlcNAcylation and phosphorylation simultaneously.
30205382	8	64	mod	modified	1476:1483	arg1	STAT3					1466:1470	STAT3	1466:1470	STAT3	1466:1470	Immunoprecipitation revealed that STAT3 was modified by O-GlcNAcylation and phosphorylation simultaneously.
30205382	8	64	mod	modified	1476:1483	arg3	phosphorylation					1508:1522	phosphorylation	1508:1522	phosphorylation	1508:1522	Immunoprecipitation revealed that STAT3 was modified by O-GlcNAcylation and phosphorylation simultaneously.
30205382	4	65	from	Effects	854:860	arg1	apoptosis					895:903	human RVEC apoptosis	884:903	human RVEC apoptosis	884:903	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	4	65	from	Effects	854:860	arg1	expression					926:935	involved protein expression	909:935	involved protein expression	909:935	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	7	66	theme	vascular	1381:1388	arg1	factor					1409:1414	vascular endothelial growth factor	1381:1414	vascular endothelial growth factor (VEGF) changes	1381:1429	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	7	66	theme	vascular	1381:1388	arg1	VEGF					1417:1420	VEGF	1417:1420	VEGF	1417:1420	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	4	67	theme	flow	955:958	arg1	cytometry					960:968	flow cytometry	955:968	flow cytometry	955:968	Effects of O-GlcNAcylation on human RVEC apoptosis and involved protein expression were assayed with flow cytometry and Western blot.
30205382	0	68	with	Identification	0:13	arg1	Phosphorylation					90:104	Phosphorylation	90:104	Phosphorylation of STAT3 in Retina Vascular Endothelium Cells	90:150	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	6	69	theme	Tyr705	1176:1181	arg1	sensitive					1192:1200	sensitive	1192:1200	sensitive	1192:1200	In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose.
30205382	6	69	theme	Tyr705	1176:1181	arg1	site					1183:1186	the Tyr705 site	1172:1186	the Tyr705 site	1172:1186	In vitro assays demonstrated that the Tyr705 site was sensitive to high glucose.
30205382	10	70	theme	diabetic	1888:1895	arg1	complications					1897:1909	other diabetic complications	1882:1909	other diabetic complications	1882:1909	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	3	71	theme	blot	839:842	arg1	analysis					844:851	Western blot analysis	831:851	Western blot analysis	831:851	The relationship between O-GlcNAcylation and STAT3 was further delineated by immunoprecipitation and Western blot analysis.
30205382	10	72	theme	complications	1897:1909	arg1	mechanisms					1861:1870	the mechanisms	1857:1870	the mechanisms of DR and other diabetic complications	1857:1909	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	1	73	from	increase	195:202	arg1	modification					249:260	O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	207:260	O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification	207:260	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	10	74	theme	other	1882:1886	arg1	complications					1897:1909	other diabetic complications	1882:1909	other diabetic complications	1882:1909	CONCLUSION: O-GlcNAcylation could relieve RVECs apoptosis through the STAT3 pathway in DR, and O-GlcNAcylation combined with STAT3 phosphorylation might open up new insights into the mechanisms of DR and other diabetic complications.
30205382	9	75	theme	RVEC	1617:1620	arg1	apoptosis					1622:1630	human RVEC apoptosis	1611:1630	human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway	1611:1675	Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway.
30205382	5	76	theme	high	1113:1116	arg1	conditions					1126:1135	high glucose conditions	1113:1135	high glucose conditions	1113:1135	RESULTS: Global O-GlcNAcylation and pSTAT3 levels were significantly elevated in diabetic rat retina and primary RVECs under high glucose conditions.
30205382	7	77	theme	factor	1409:1414	arg1	changes					1423:1429	vascular endothelial growth factor (VEGF) changes	1381:1429	vascular endothelial growth factor (VEGF) changes	1381:1429	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	9	78	theme	JAK2-Tyr705STAT3-VEGF	1647:1667	arg1	pathway					1669:1675	the JAK2-Tyr705STAT3-VEGF pathway	1643:1675	the JAK2-Tyr705STAT3-VEGF pathway	1643:1675	Next, we observed that overexpression of O-GlcNAcylation could relieve human RVEC apoptosis related to the JAK2-Tyr705STAT3-VEGF pathway.
30205382	7	79	theme	p705STAT3	1313:1321	arg1	expression					1323:1332	p705STAT3 expression	1313:1332	p705STAT3 expression	1313:1332	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	0	80	from	Modification	34:45	arg1	Retinopathy					59:69	Diabetic Retinopathy	50:69	Diabetic Retinopathy	50:69	Identification of O-GlcNAcylation Modification in Diabetic Retinopathy and Crosstalk with Phosphorylation of STAT3 in Retina Vascular Endothelium Cells.
30205382	2	81	located	detected	679:686	arg2	effects					597:603	their potential effects	581:603	their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3	581:672	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	2	81	located	detected	679:686	arg1	tissues					703:709	DR-affected tissues	691:709	DR-affected tissues	691:709	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	2	81	located	detected	679:686	arg1	RVECs					723:727	primary RVECs	715:727	primary RVECs	715:727	In this study, we focused on the correlations between O-GlcNAcylation and STAT3 phosphorylation, and their potential effects with regards to DR. METHODS: Expression of O-GlcNAcylation and STAT3 were detected in DR-affected tissues and primary RVECs.
30205382	7	82	theme	high	1352:1355	arg1	levels					1357:1362	relatively high levels	1341:1362	relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes	1341:1429	While O-GlcNAcylation inhibited p727STAT3 expression, augmented O-GlcNAcylation could balance p705STAT3 expression within relatively high levels corresponding to vascular endothelial growth factor (VEGF) changes.
30205382	1	83	theme	signal	267:272	arg1	STAT3					328:332	STAT3	328:332	STAT3	328:332	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
30205382	1	83	theme	signal	267:272	arg1	transducer					274:283	signal transducer	267:283	signal transducer	267:283	BACKGROUND/AIMS: Recently, we observed an increase in O-GlcNAc (O-linked-ß-N-acetylglucosamine) modification, and signal transducer and activator of transcription proteins 3 (STAT3) expression in primary retinal vascular endothelial cells (RVECs) under high glucose conditions and tissues altered by diabetic retinopathy (DR).
29302041	7	0	dep	less	935:938	arg1	IgE					940:942	IgE	940:942	IgE	940:942	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	7	1	theme	HgbβmiKO	998:1005	arg1	mice					1007:1010	HgbβmiKO mice	998:1010	HgbβmiKO mice	998:1010	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	3	2	theme	fetal	484:488	arg1	chain					495:499	the most prominent fetal Hgbβ chain	465:499	the most prominent fetal Hgbβ chain	465:499	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	3	2	theme	fetal	484:488	arg1	Hgbβmi					455:460	Hgbβmi	455:460	Hgbβmi	455:460	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	6	3	theme	higher	803:808	arg1	ratio					820:824	a higher IL-2:IL-4 ratio	801:824	a higher IL-2:IL-4 ratio	801:824	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	9	4	from	chains	1361:1366	arg1	absent					1342:1347	absent	1342:1347	absent	1342:1347	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	10	5	theme	unanticipated	1401:1413	arg1	function					1426:1433	a previously unanticipated biological function	1388:1433	a previously unanticipated biological function of a naturally secreted fetal Hgb chain	1388:1473	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	10	5	theme	unanticipated	1401:1413	arg1	responsible					1489:1499	responsible	1489:1499	responsible	1489:1499	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	9	6	theme	N-linked	1292:1299	arg1	sites					1315:1319	the two N-linked glycosylation sites	1284:1319	the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains	1284:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	2	7	with	mice	366:369	arg1	deletions					386:394	homzygous deletions	376:394	homzygous deletions	376:394	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	10	8	theme	secreted	1450:1457	arg1	chain					1469:1473	a naturally secreted fetal Hgb chain	1438:1473	a naturally secreted fetal Hgb chain	1438:1473	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	5	9	used	used	655:658	arg2	cells					609:613	CHO cells	605:613	CHO cells transfected with cloned Hgb chains	605:648	CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes.
29302041	1	10	theme	crude	174:178	arg1	FSLE					207:210	FSLE	207:210	FSLE	207:210	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	10	theme	crude	174:178	arg1	extract					198:204	a crude fetal sheep liver extract	172:204	a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH)	172:269	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	9	11	from	absent	1342:1347	arg1	chains					1361:1366	the Hgbβ chains	1352:1366	the Hgbβ chains	1352:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	8	12	theme	fetal	1145:1149	arg1	Hgbε					1162:1165	Hgbε	1162:1165	Hgbε	1162:1165	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	8	12	theme	fetal	1145:1149	arg1	chain					1155:1159	only the fetal Hgb chain	1136:1159	only the fetal Hgb chain	1136:1159	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	1	13	theme	sheep	186:190	arg1	FSLE					207:210	FSLE	207:210	FSLE	207:210	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	13	theme	sheep	186:190	arg1	extract					198:204	a crude fetal sheep liver extract	172:204	a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH)	172:269	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	8	14	theme	Hgb	1110:1112	arg1	chains					1114:1119	cloned Hgb chains	1103:1119	cloned Hgb chains	1103:1119	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	0	15	from	stimuli	73:79	arg1	mice					84:87	mice	84:87	mice with genetic defects in fetal and adult hemoglobin chain expression	84:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	4	16	theme	Hgb	571:573	arg1	HgbεKO					582:587	HgbεKO	582:587	HgbεKO	582:587	Mice lacking another fetal Hgb chain, HgbεKO, died in utero.
29302041	4	16	theme	Hgb	571:573	arg1	chain					575:579	another fetal Hgb chain	557:579	another fetal Hgb chain	557:579	Mice lacking another fetal Hgb chain, HgbεKO, died in utero.
29302041	7	17	theme	allergic-type	1045:1057	arg1	responses					1059:1067	heightened allergic-type responses	1034:1067	heightened allergic-type responses	1034:1067	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	7	18	theme	HgbβmaKO	912:919	arg1	mice					921:924	HgbβmaKO mice	912:924	HgbβmaKO mice	912:924	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	1	19	theme	extract	198:204	arg1	Injections					158:167	Injections	158:167	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH)	158:269	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	6	20	theme	HgbβmiKO	842:849	arg1	mice					851:854	HgbβmiKO mice	842:854	HgbβmiKO mice	842:854	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	9	21	gly	glycosylation	1301:1313	arg2	two					1288:1290	two	1288:1290	two	1288:1290	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	9	21	gly	glycosylation	1301:1313	arg2	sites					1315:1319	the two N-linked glycosylation sites	1284:1319	the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains	1284:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	10	22	theme	Hgb	1465:1467	arg1	chain					1469:1473	a naturally secreted fetal Hgb chain	1438:1473	a naturally secreted fetal Hgb chain	1438:1473	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	0	23	theme	hemoglobin	129:138	arg1	expression					146:155	fetal and adult hemoglobin chain expression	113:155	fetal and adult hemoglobin chain expression	113:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	9	24	theme	absent	1342:1347	arg1	sites					1315:1319	the two N-linked glycosylation sites	1284:1319	the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains	1284:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	9	25	dep	Hgbβma	1210:1215	arg1	chains					1227:1232	chains	1227:1232	chains	1227:1232	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	7	26	from	immunization	867:878	arg1	alum					906:909	alum	906:909	alum	906:909	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	11	27	theme	rabbit	1614:1619	arg1	anti-Hgbε					1621:1629	rabbit anti-Hgbε	1614:1629	rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi	1614:1671	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	1	28	theme	aged	300:303	arg1	mice					305:308	aged mice	300:308	aged mice	300:308	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	0	29	from	Analysis	0:7	arg1	response					48:55	response	48:55	response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression	48:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	5	30	theme	Hgb	639:641	arg1	chains					643:648	cloned Hgb chains	632:648	cloned Hgb chains	632:648	CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes.
29302041	3	31	from	mice	538:541	arg1	prominent					519:527	prominent	519:527	prominent	519:527	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	2	32	theme	hemoglobin	344:353	arg1	role					330:333	the role	326:333	the role of fetal hemoglobin	326:353	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	0	33	theme	genetic	94:100	arg1	defects					102:108	genetic defects	94:108	genetic defects in fetal and adult hemoglobin chain expression	94:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	11	34	theme	higher	1726:1731	arg1	ratios					1743:1748	the higher IL-2:IL-4 ratios	1722:1748	the higher IL-2:IL-4 ratios seen in HgbβmiKO mice	1722:1770	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	9	35	link	N-linked	1292:1299	arg1	sites					1315:1319	the two N-linked glycosylation sites	1284:1319	the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains	1284:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	10	36	dep	fetal	1562:1566	arg1	adult					1573:1577	adult	1573:1577	adult	1573:1577	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	0	37	theme	cytokine	12:19	arg1	profile					37:43	cytokine immune response profile	12:43	cytokine immune response profile	12:43	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	2	38	theme	major	418:422	arg1	HgbβmaKO					433:440	HgbβmaKO	433:440	HgbβmaKO	433:440	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	2	38	theme	major	418:422	arg1	βchains					424:430	the two major βchains	410:430	the two major βchains	410:430	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	2	38	theme	major	418:422	arg1	HgbβmiKO					445:452	HgbβmiKO	445:452	HgbβmiKO	445:452	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	2	39	dep	derived	358:364	arg1	investigate					314:324	investigate	314:324	To investigate the role of fetal hemoglobin	311:353	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	0	40	theme	response	28:35	arg1	profile					37:43	cytokine immune response profile	12:43	cytokine immune response profile	12:43	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	7	41	theme	heightened	1034:1043	arg1	responses					1059:1067	heightened allergic-type responses	1034:1067	heightened allergic-type responses	1034:1067	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	9	42	from	Hgbε	1332:1335	arg1	present					1321:1327	present	1321:1327	present	1321:1327	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	10	43	theme	fetal	1562:1566	arg1	Hgb					1580:1582	fetal, not adult, Hgb	1562:1582	fetal, not adult, Hgb	1562:1582	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	5	44	theme	rabbit	699:704	arg1	heteroantibodes					706:720	rabbit heteroantibodes	699:720	rabbit heteroantibodes	699:720	CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes.
29302041	9	45	from	present	1321:1327	arg1	Hgbε					1332:1335	Hgbε	1332:1335	Hgbε	1332:1335	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	6	46	from	mice	851:854	arg1	cells					831:835	cells	831:835	cells from HgbβmiKO mice	831:854	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	10	47	theme	animals	1549:1555	arg1	injection					1536:1544	injection	1536:1544	injection of animals with fetal, not adult, Hgb	1536:1582	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	7	48	theme	mice	1007:1010	arg1	absence					987:993	the absence	983:993	the absence of HgbβmiKO mice	983:1010	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	1	49	theme	fetal	224:228	arg1	hemoglobin					230:239	fetal hemoglobin	224:239	fetal hemoglobin	224:239	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	6	50	theme	IL-4	815:818	arg1	ratio					820:824	a higher IL-2:IL-4 ratio	801:824	a higher IL-2:IL-4 ratio	801:824	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	3	51	theme	prominent	474:482	arg1	chain					495:499	the most prominent fetal Hgbβ chain	465:499	the most prominent fetal Hgbβ chain	465:499	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	3	51	theme	prominent	474:482	arg1	Hgbβmi					455:460	Hgbβmi	455:460	Hgbβmi	455:460	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	6	52	theme	IL-2	810:813	arg1	ratio					820:824	a higher IL-2:IL-4 ratio	801:824	a higher IL-2:IL-4 ratio	801:824	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	10	53	theme	biological	1415:1424	arg1	function					1426:1433	a previously unanticipated biological function	1388:1433	a previously unanticipated biological function of a naturally secreted fetal Hgb chain	1388:1473	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	10	53	theme	biological	1415:1424	arg1	responsible					1489:1499	responsible	1489:1499	responsible	1489:1499	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	10	54	with	injection	1536:1544	arg1	Hgb					1580:1582	fetal, not adult, Hgb	1562:1582	fetal, not adult, Hgb	1562:1582	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	10	55	theme	fetal	1459:1463	arg1	chain					1469:1473	a naturally secreted fetal Hgb chain	1438:1473	a naturally secreted fetal Hgb chain	1438:1473	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	9	56	theme	glycosylation	1301:1313	arg1	sites					1315:1319	the two N-linked glycosylation sites	1284:1319	the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains	1284:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	8	57	theme	CHO	1076:1078	arg1	cells					1080:1084	CHO cells	1076:1084	CHO cells transfected with cloned Hgb chains	1076:1119	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	11	58	theme	anti-Hgbβma	1646:1656	arg1	injections					1600:1609	injections	1600:1609	injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi	1600:1671	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	5	59	theme	CHO	605:607	arg1	cells					609:613	CHO cells	605:613	CHO cells transfected with cloned Hgb chains	605:648	CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes.
29302041	0	60	with	mice	84:87	arg1	defects					102:108	genetic defects	94:108	genetic defects in fetal and adult hemoglobin chain expression	94:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	3	61	theme	Hgbβ	490:493	arg1	chain					495:499	the most prominent fetal Hgbβ chain	465:499	the most prominent fetal Hgbβ chain	465:499	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	3	61	theme	Hgbβ	490:493	arg1	Hgbβmi					455:460	Hgbβmi	455:460	Hgbβmi	455:460	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	1	62	theme	fetal	180:184	arg1	FSLE					207:210	FSLE	207:210	FSLE	207:210	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	62	theme	fetal	180:184	arg1	extract					198:204	a crude fetal sheep liver extract	172:204	a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH)	172:269	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	6	63	from	mice	749:752	arg1	Splenocytes					723:733	Splenocytes	723:733	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A	723:792	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	7	64	theme	HgbβmiKO	949:956	arg1	mice					958:961	HgbβmiKO mice	949:961	HgbβmiKO mice	949:961	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	3	65	theme	prominent	519:527	arg1	chain					495:499	the most prominent fetal Hgbβ chain	465:499	the most prominent fetal Hgbβ chain	465:499	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	3	65	theme	prominent	519:527	arg1	Hgbβmi					455:460	Hgbβmi	455:460	Hgbβmi	455:460	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	1	66	theme	liver	192:196	arg1	FSLE					207:210	FSLE	207:210	FSLE	207:210	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	66	theme	liver	192:196	arg1	extract					198:204	a crude fetal sheep liver extract	172:204	a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH)	172:269	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	8	67	theme	cloned	1103:1108	arg1	chains					1114:1119	cloned Hgb chains	1103:1119	cloned Hgb chains	1103:1119	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	8	68	theme	Hgb	1151:1153	arg1	Hgbε					1162:1165	Hgbε	1162:1165	Hgbε	1162:1165	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	8	68	theme	Hgb	1151:1153	arg1	chain					1155:1159	only the fetal Hgb chain	1136:1159	only the fetal Hgb chain	1136:1159	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	10	69	theme	chain	1469:1473	arg1	function					1426:1433	a previously unanticipated biological function	1388:1433	a previously unanticipated biological function of a naturally secreted fetal Hgb chain	1388:1473	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	10	69	theme	chain	1469:1473	arg1	responsible					1489:1499	responsible	1489:1499	responsible	1489:1499	We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb.
29302041	11	70	theme	day	1678:1680	arg1	gestation					1685:1693	day 14 gestation	1678:1693	day 14 gestation	1678:1693	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	0	71	theme	chain	140:144	arg1	expression					146:155	fetal and adult hemoglobin chain expression	113:155	fetal and adult hemoglobin chain expression	113:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	7	72	with	immunization	867:878	arg1	ovalbumin					893:901	ovalbumin	893:901	ovalbumin	893:901	Following immunization in vivo with ovalbumin in alum, HgbβmaKO mice produced less IgE than HgbβmiKO mice, suggesting that in the absence of HgbβmiKO mice had a predeliction to heightened allergic-type responses.
29302041	0	73	theme	fetal	113:117	arg1	expression					146:155	fetal and adult hemoglobin chain expression	113:155	fetal and adult hemoglobin chain expression	113:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	0	74	from	defects	102:108	arg1	expression					146:155	fetal and adult hemoglobin chain expression	113:155	fetal and adult hemoglobin chain expression	113:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	0	75	theme	inflammatory	60:71	arg1	stimuli					73:79	inflammatory stimuli	60:79	inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression	60:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	3	76	theme	adult	532:536	arg1	mice					538:541	adult mice	532:541	adult mice	532:541	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	9	77	theme	present	1321:1327	arg1	sites					1315:1319	the two N-linked glycosylation sites	1284:1319	the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains	1284:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	9	78	theme	Hgbβ	1356:1359	arg1	chains					1361:1366	the Hgbβ chains	1352:1366	the Hgbβ chains	1352:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	8	79	theme	high	1184:1187	arg1	levels					1189:1194	high levels	1184:1194	high levels	1184:1194	Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels.
29302041	11	80	theme	anti-Hgbε	1621:1629	arg1	injections					1600:1609	injections	1600:1609	injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi	1600:1671	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	5	81	theme	cloned	632:637	arg1	chains					643:648	cloned Hgb chains	632:648	cloned Hgb chains	632:648	CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes.
29302041	3	82	with	prominent	519:527	arg1	Hgbβma					507:512	Hgbβma	507:512	Hgbβma	507:512	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	9	83	attach	present	1321:1327	arg1	Hgbε					1332:1335	Hgbε	1332:1335	Hgbε	1332:1335	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	9	83	attach	present	1321:1327	arg2	sites					1315:1319	the two N-linked glycosylation sites	1284:1319	the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains	1284:1366	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	2	84	theme	fetal	338:342	arg1	hemoglobin					344:353	fetal hemoglobin	338:353	fetal hemoglobin	338:353	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	5	85	theme	heteroantibodes	706:720	arg1	preparation					684:694	preparation	684:694	preparation of rabbit heteroantibodes	684:720	CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes.
29302041	0	86	theme	adult	123:127	arg1	expression					146:155	fetal and adult hemoglobin chain expression	113:155	fetal and adult hemoglobin chain expression	113:155	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	6	87	theme	HgbβmaKO	740:747	arg1	mice					749:752	HgbβmaKO mice	740:752	HgbβmaKO mice stimulated in vitro with Conconavalin A	740:792	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	11	88	theme	IL-2	1733:1736	arg1	ratios					1743:1748	the higher IL-2:IL-4 ratios	1722:1748	the higher IL-2:IL-4 ratios seen in HgbβmiKO mice	1722:1770	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	0	89	theme	immune	21:26	arg1	profile					37:43	cytokine immune response profile	12:43	cytokine immune response profile	12:43	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	1	90	contain	containing	213:222	arg2	hemoglobin					230:239	fetal hemoglobin	224:239	fetal hemoglobin	224:239	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	90	contain	containing	213:222	arg1	FSLE					207:210	FSLE	207:210	FSLE	207:210	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	90	contain	containing	213:222	arg2	glutathione					252:262	glutathione	252:262	glutathione (GSSH)	252:269	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	90	contain	containing	213:222	arg2	MPLA					242:245	MPLA	242:245	MPLA	242:245	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	90	contain	containing	213:222	arg2	GSSH					265:268	GSSH	265:268	GSSH	265:268	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	1	90	contain	containing	213:222	arg1	extract					198:204	a crude fetal sheep liver extract	172:204	a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH)	172:269	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	2	91	theme	homzygous	376:384	arg1	deletions					386:394	homzygous deletions	376:394	homzygous deletions	376:394	To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO.
29302041	3	92	from	prominent	519:527	arg1	mice					538:541	adult mice	532:541	adult mice	532:541	Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice.
29302041	11	93	theme	HgbβmiKO	1758:1765	arg1	mice					1767:1770	HgbβmiKO mice	1758:1770	HgbβmiKO mice	1758:1770	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	0	94	theme	profile	37:43	arg1	Analysis					0:7	Analysis	0:7	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.	0:156	Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
29302041	9	95	theme	Hgbβma	1210:1215	arg1	Secretion					1197:1205	Secretion	1197:1205	Secretion of Hgbβma or Hgbβmi chains	1197:1232	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	6	96	theme	Conconavalin	779:790	arg1	A					792:792	Conconavalin A	779:792	Conconavalin A	779:792	Splenocytes from HgbβmaKO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from HgbβmiKO mice.
29302041	1	97	from	changes	289:295	arg1	mice					305:308	aged mice	300:308	aged mice	300:308	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	9	98	theme	Hgbβmi	1220:1225	arg1	Secretion					1197:1205	Secretion	1197:1205	Secretion of Hgbβma or Hgbβmi chains	1197:1232	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29302041	1	99	theme	cytokine	280:287	arg1	changes					289:295	cytokine changes	280:295	cytokine changes in aged mice	280:308	Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice.
29302041	4	100	theme	fetal	565:569	arg1	HgbεKO					582:587	HgbεKO	582:587	HgbεKO	582:587	Mice lacking another fetal Hgb chain, HgbεKO, died in utero.
29302041	4	100	theme	fetal	565:569	arg1	chain					575:579	another fetal Hgb chain	557:579	another fetal Hgb chain	557:579	Mice lacking another fetal Hgb chain, HgbεKO, died in utero.
29302041	11	101	theme	IL-4	1738:1741	arg1	ratios					1743:1748	the higher IL-2:IL-4 ratios	1722:1748	the higher IL-2:IL-4 ratios seen in HgbβmiKO mice	1722:1770	Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβma or anti-Hgbβmi from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in HgbβmiKO mice.
29302041	9	102	theme	genetic	1254:1260	arg1	mutation					1262:1269	genetic mutation	1254:1269	genetic mutation	1254:1269	Secretion of Hgbβma or Hgbβmi chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains.
29339411	2	0	from	information	460:470	arg1	factors					489:495	its virulence factors	475:495	its virulence factors	475:495	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	2	0	from	information	460:470	arg1	mechanisms					526:535	underlying pathogenicity mechanisms	501:535	underlying pathogenicity mechanisms	501:535	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	1	1	theme	system	307:312	arg1	colonizers					279:288	colonizers	279:288	colonizers	279:288	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	1	1	theme	system	307:312	arg1	species					267:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species	200:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species	200:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	3	2	theme	glycoprotein	598:609	arg1	report					574:579	the first report	564:579	the first report of a Selenomonas glycoprotein	564:609	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	13	3	theme	under-investigated	2340:2357	arg1	properties					2367:2376	the largely under-investigated surface properties	2328:2376	the largely under-investigated surface properties of oral bacteria	2328:2393	This study contributes to our understanding of the largely under-investigated surface properties of oral bacteria.
29339411	4	4	theme	glycan	944:949	arg1	macro-					951:956	extensive glycan macro-	934:956	extensive glycan macro-	934:956	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	3	5	link	linked	809:814	arg1	O-glycans					816:824	N-acetylglucosamine linked O-glycans	789:824	N-acetylglucosamine linked O-glycans	789:824	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	5	6	dep	protein	1135:1141	arg1	Thr199					1160:1165	Thr199	1160:1165	Thr199	1160:1165	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	6	dep	protein	1135:1141	arg1	Ser182					1152:1157	Ser182	1152:1157	Ser182	1152:1157	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	6	dep	protein	1135:1141	arg1	Thr149					1144:1149	Thr149	1144:1149	Thr149	1144:1149	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	6	dep	protein	1135:1141	arg1	Thr259					1168:1173	Thr259	1168:1173	Thr259	1168:1173	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	6	dep	protein	1135:1141	arg1	Ser334					1180:1185	Ser334	1180:1185	Ser334	1180:1185	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	10	7	dep	CID	1777:1779	arg1	ions					1789:1792	oxonium ions	1781:1792	oxonium ions	1781:1792	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	0	8	theme	Fragment	145:152	arg1	Rearrangement					154:166	Rhamnose Fragment Rearrangement	136:166	Rhamnose Fragment Rearrangement	136:166	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides.
29339411	10	9	theme	electron	1798:1805	arg1	dissociation					1816:1827	electron transfer dissociation	1798:1827	electron transfer dissociation	1798:1827	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	3	10	theme	diversely	649:657	arg1	protein					723:729	a major cellular protein	706:729	a major cellular protein	706:729	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	10	theme	diversely	649:657	arg1	C9LY14					696:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	12	11	theme	O-linked	2130:2137	arg1	glycosylation					2149:2161	O-linked flagellin glycosylation	2130:2161	O-linked flagellin glycosylation	2130:2161	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	4	12	theme	glycopeptide	1007:1018	arg1	species					1020:1026	22 unique glycopeptide species	997:1026	22 unique glycopeptide species	997:1026	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	8	13	theme	glycopeptide	1609:1620	arg1	ions					1622:1625	protonated glycopeptide ions	1598:1625	protonated glycopeptide ions	1598:1625	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	12	14	theme	flagellins	2251:2260	arg1	flagellins					2251:2260	the most heavily glycosylated flagellins	2221:2260	the most heavily glycosylated flagellins described to date	2221:2278	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	12	14	theme	flagellins	2251:2260	arg1	one					2214:2216	one	2214:2216	one	2214:2216	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	9	15	theme	pseudo	1652:1657	arg1	ions					1684:1687	pseudo Y1-glycopeptide fragment ions	1652:1687	pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide	1652:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	3	16	theme	flagellin	686:694	arg1	protein					723:729	a major cellular protein	706:729	a major cellular protein	706:729	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	16	theme	flagellin	686:694	arg1	C9LY14					696:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	12	17	link	O-linked	2130:2137	arg1	glycosylation					2149:2161	O-linked flagellin glycosylation	2130:2161	O-linked flagellin glycosylation	2130:2161	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	9	18	theme	fragment	1675:1682	arg1	ions					1684:1687	pseudo Y1-glycopeptide fragment ions	1652:1687	pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide	1652:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	5	19	theme	multiple	1038:1045	arg1	glycosylation					1056:1068	glycosylation	1056:1068	glycosylation	1056:1068	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	19	theme	multiple	1038:1045	arg1	sites					1047:1051	the multiple sites	1034:1051	the multiple sites of glycosylation	1034:1068	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	7	20	theme	sputigena	1473:1481	arg1	flagellin					1483:1491	native S. sputigena flagellin	1463:1491	native S. sputigena flagellin	1463:1491	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	3	21	gly	glycoprotein	598:609	arg1	glycoprotein					598:609	a Selenomonas glycoprotein	584:609	a Selenomonas glycoprotein	584:609	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	7	22	theme	undescribed	1349:1359	arg1	residues/modifications					1361:1382	hitherto undescribed residues/modifications	1340:1382	hitherto undescribed residues/modifications	1340:1382	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	5	23	theme	flagellin	1198:1206	arg1	protein					1208:1214	the only flagellin protein	1189:1214	the only flagellin protein identified	1189:1225	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	23	theme	flagellin	1198:1206	arg1	protein					1135:1141	the 437-amino acid C9LY14 protein	1109:1141	the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334)	1109:1186	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	4	24	gly	glycopeptide	1007:1018	arg2	glycopeptide					1007:1018	22 unique glycopeptide species	997:1026	22 unique glycopeptide species	997:1026	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	1	25	theme	Flagellated	200:210	arg1	colonizers					279:288	colonizers	279:288	colonizers	279:288	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	1	25	theme	Flagellated	200:210	arg1	species					267:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species	200:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species	200:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	9	26	from	presence	1708:1715	arg1	glycopeptide					1763:1774	a single glycopeptide	1754:1774	a single glycopeptide	1754:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	5	27	gly	glycosylation	1056:1068	arg2	sites					1047:1051	the multiple sites	1034:1051	the multiple sites of glycosylation	1034:1068	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	27	gly	glycosylation	1056:1068	arg2	glycosylation					1056:1068	glycosylation	1056:1068	glycosylation	1056:1068	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	9	28	gly	Y1-glycopeptide	1659:1673	arg2	Y1-glycopeptide					1659:1673	pseudo Y1-glycopeptide fragment ions	1652:1687	pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide	1652:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	3	29	from	O-glycans	816:824	arg1	mono-					844:848	mono-	844:848	mono-	844:848	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	29	from	O-glycans	816:824	arg1	range					833:837	the range	829:837	the range from mono- to hexasaccharides	829:867	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	9	30	theme	glycosylation	1731:1743	arg1	sites					1745:1749	additional glycosylation sites	1720:1749	additional glycosylation sites	1720:1749	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	7	31	theme	S.	1470:1471	arg1	flagellin					1483:1491	native S. sputigena flagellin	1463:1491	native S. sputigena flagellin	1463:1491	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	2	32	theme	human	428:432	arg1	pathogen					446:453	a potential human periodontal pathogen	416:453	a potential human periodontal pathogen	416:453	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	0	33	theme	Flagellin	0:8	arg1	Glycoproteomics					10:24	Flagellin Glycoproteomics	0:24	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena	0:87	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides.
29339411	5	34	theme	glycosylation	1056:1068	arg1	glycosylation					1056:1068	glycosylation	1056:1068	glycosylation	1056:1068	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	34	theme	glycosylation	1056:1068	arg1	sites					1047:1051	the multiple sites	1034:1051	the multiple sites of glycosylation	1034:1068	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	10	35	theme	moiety	2036:2041	arg1	nature					2015:2020	the molecular nature	2001:2020	the molecular nature of the glycan moiety	2001:2041	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	2	36	theme	virulence	479:487	arg1	factors					489:495	its virulence factors	475:495	its virulence factors	475:495	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	8	37	theme	monosaccharide	1513:1526	arg1	rearrangement					1528:1540	monosaccharide rearrangement	1513:1540	monosaccharide rearrangement	1513:1540	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	10	38	gly	glycopeptides	1949:1961	arg2	glycopeptides					1949:1961	glycopeptides	1949:1961	glycopeptides	1949:1961	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	9	39	theme	single	1756:1761	arg1	glycopeptide					1763:1774	a single glycopeptide	1754:1774	a single glycopeptide	1754:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	7	40	theme	high	1445:1448	arg1	diversity					1450:1458	the high diversity	1441:1458	the high diversity of native S. sputigena flagellin	1441:1491	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	3	41	theme	major	708:712	arg1	protein					723:729	a major cellular protein	706:729	a major cellular protein	706:729	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	41	theme	major	708:712	arg1	C9LY14					696:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	4	42	theme	glycoproteomic	899:912	arg1	assessment					914:923	A comprehensive glycomic and glycoproteomic assessment	870:923	A comprehensive glycomic and glycoproteomic assessment	870:923	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	0	43	theme	Periodontitis	33:45	arg1	Pathogen					58:65	the Periodontitis Associated Pathogen	29:65	the Periodontitis Associated Pathogen	29:65	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides.
29339411	13	44	theme	bacteria	2386:2393	arg1	properties					2367:2376	the largely under-investigated surface properties	2328:2376	the largely under-investigated surface properties of oral bacteria	2328:2393	This study contributes to our understanding of the largely under-investigated surface properties of oral bacteria.
29339411	2	45	theme	pathogenicity	512:524	arg1	mechanisms					526:535	underlying pathogenicity mechanisms	501:535	underlying pathogenicity mechanisms	501:535	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	8	46	theme	collision-induced	1558:1574	arg1	CID					1590:1592	CID	1590:1592	CID	1590:1592	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	8	46	theme	collision-induced	1558:1574	arg1	dissociation					1576:1587	collision-induced dissociation	1558:1587	collision-induced dissociation (CID) of protonated glycopeptide ions	1558:1625	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	0	47	theme	Pathogen	58:65	arg1	Glycoproteomics					10:24	Flagellin Glycoproteomics	0:24	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena	0:87	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides.
29339411	12	48	gly	glycosylated	2238:2249	arg1	flagellins					2251:2260	the most heavily glycosylated flagellins	2221:2260	the most heavily glycosylated flagellins described to date	2221:2278	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	6	49	theme	putative	1295:1302	arg1	acetylation					1304:1314	putative acetylation	1295:1314	putative acetylation	1295:1314	The O-glycans additionally showed modifications by methylation and putative acetylation.
29339411	13	50	theme	surface	2359:2365	arg1	properties					2367:2376	the largely under-investigated surface properties	2328:2376	the largely under-investigated surface properties of oral bacteria	2328:2393	This study contributes to our understanding of the largely under-investigated surface properties of oral bacteria.
29339411	12	51	from	report	2120:2125	arg1	glycosylation					2149:2161	O-linked flagellin glycosylation	2130:2161	O-linked flagellin glycosylation	2130:2161	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	12	51	from	report	2120:2125	arg1	species					2180:2186	a Selenomonas species	2166:2186	a Selenomonas species	2166:2186	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	5	52	theme	437-amino	1113:1121	arg1	protein					1208:1214	the only flagellin protein	1189:1214	the only flagellin protein identified	1189:1225	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	52	theme	437-amino	1113:1121	arg1	protein					1135:1141	the 437-amino acid C9LY14 protein	1109:1141	the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334)	1109:1186	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	7	53	theme	respective	1407:1416	arg1	values					1422:1427	their respective m/z values	1401:1427	their respective m/z values	1401:1427	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	9	54	gly	glycopeptide	1763:1774	arg2	glycopeptide					1763:1774	a single glycopeptide	1754:1774	a single glycopeptide	1754:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	4	55	theme	glycomic	886:893	arg1	assessment					914:923	A comprehensive glycomic and glycoproteomic assessment	870:923	A comprehensive glycomic and glycoproteomic assessment	870:923	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	10	56	theme	glycan-to-peptide	1904:1920	arg1	rearrangement					1922:1934	glycan-to-peptide rearrangement	1904:1934	glycan-to-peptide rearrangement	1904:1934	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	5	57	theme	C9LY14	1128:1133	arg1	protein					1208:1214	the only flagellin protein	1189:1214	the only flagellin protein identified	1189:1225	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	57	theme	C9LY14	1128:1133	arg1	protein					1135:1141	the 437-amino acid C9LY14 protein	1109:1141	the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334)	1109:1186	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	10	58	theme	oxonium	1781:1787	arg1	ions					1789:1792	oxonium ions	1781:1792	oxonium ions	1781:1792	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	3	59	theme	undescribed	763:773	arg1	rhamnose-					775:783	hitherto undescribed rhamnose-	754:783	hitherto undescribed rhamnose-	754:783	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	1	60	theme	digestive	297:305	arg1	system					307:312	the digestive system	293:312	the digestive system	293:312	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	3	61	theme	various	746:752	arg1	rhamnose-					775:783	hitherto undescribed rhamnose-	754:783	hitherto undescribed rhamnose-	754:783	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	62	theme	Selenomonas	586:596	arg1	glycoprotein					598:609	a Selenomonas glycoprotein	584:609	a Selenomonas glycoprotein	584:609	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	12	63	theme	Selenomonas	2168:2178	arg1	species					2180:2186	a Selenomonas species	2166:2186	a Selenomonas species	2166:2186	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	3	64	theme	linked	809:814	arg1	O-glycans					816:824	N-acetylglucosamine linked O-glycans	789:824	N-acetylglucosamine linked O-glycans	789:824	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	4	65	theme	extensive	934:942	arg1	macro-					951:956	extensive glycan macro-	934:956	extensive glycan macro-	934:956	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	3	66	gly	O-glycosylated	671:684	arg1	protein					723:729	a major cellular protein	706:729	a major cellular protein	706:729	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	66	gly	O-glycosylated	671:684	arg1	C9LY14					696:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	67	from	rhamnose-	775:783	arg1	mono-					844:848	mono-	844:848	mono-	844:848	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	67	from	rhamnose-	775:783	arg1	range					833:837	the range	829:837	the range from mono- to hexasaccharides	829:867	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	8	68	gly	glycopeptide	1609:1620	arg2	glycopeptide					1609:1620	protonated glycopeptide ions	1598:1625	protonated glycopeptide ions	1598:1625	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	12	69	theme	flagellin	2139:2147	arg1	glycosylation					2149:2161	O-linked flagellin glycosylation	2130:2161	O-linked flagellin glycosylation	2130:2161	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	8	70	theme	protonated	1598:1607	arg1	ions					1622:1625	protonated glycopeptide ions	1598:1625	protonated glycopeptide ions	1598:1625	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	10	71	theme	transfer	1807:1814	arg1	dissociation					1816:1827	electron transfer dissociation	1798:1827	electron transfer dissociation	1798:1827	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	1	72	theme	Selenomonas	255:265	arg1	colonizers					279:288	colonizers	279:288	colonizers	279:288	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	1	72	theme	Selenomonas	255:265	arg1	species					267:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species	200:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species	200:273	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	12	73	theme	first	2114:2118	arg1	study					2101:2105	This study	2096:2105	This study	2096:2105	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	12	73	theme	first	2114:2118	arg1	report					2120:2125	the first report	2110:2125	the first report on O-linked flagellin glycosylation in a Selenomonas species	2110:2186	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	8	74	theme	ions	1622:1625	arg1	CID					1590:1592	CID	1590:1592	CID	1590:1592	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	8	74	theme	ions	1622:1625	arg1	dissociation					1576:1587	collision-induced dissociation	1558:1587	collision-induced dissociation (CID) of protonated glycopeptide ions	1558:1625	We also found that monosaccharide rearrangement occurred during collision-induced dissociation (CID) of protonated glycopeptide ions.
29339411	11	75	with	pronounced	2065:2074	arg1	disaccharides					2081:2093	disaccharides	2081:2093	disaccharides	2081:2093	This effect was most pronounced with disaccharides.
29339411	4	76	theme	unique	1000:1005	arg1	species					1020:1026	22 unique glycopeptide species	997:1026	22 unique glycopeptide species	997:1026	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	12	77	theme	glycosylated	2238:2249	arg1	flagellins					2251:2260	the most heavily glycosylated flagellins	2221:2260	the most heavily glycosylated flagellins described to date	2221:2278	This study is the first report on O-linked flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of the most heavily glycosylated flagellins described to date.
29339411	3	78	theme	O-glycosylated	671:684	arg1	protein					723:729	a major cellular protein	706:729	a major cellular protein	706:729	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	78	theme	O-glycosylated	671:684	arg1	C9LY14					696:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	9	79	theme	Y1-glycopeptide	1659:1673	arg1	ions					1684:1687	pseudo Y1-glycopeptide fragment ions	1652:1687	pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide	1652:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	10	80	theme	molecular	2005:2013	arg1	nature					2015:2020	the molecular nature	2001:2020	the molecular nature of the glycan moiety	2001:2041	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	7	81	theme	flagellin	1483:1491	arg1	diversity					1450:1458	the high diversity	1441:1458	the high diversity of native S. sputigena flagellin	1441:1491	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	3	82	contain	carries	738:744	arg1	protein					723:729	a major cellular protein	706:729	a major cellular protein	706:729	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	82	contain	carries	738:744	arg1	C9LY14					696:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	82	contain	carries	738:744	arg2	rhamnose-					775:783	hitherto undescribed rhamnose-	754:783	hitherto undescribed rhamnose-	754:783	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	82	contain	carries	738:744	arg2	O-glycans					816:824	N-acetylglucosamine linked O-glycans	789:824	N-acetylglucosamine linked O-glycans	789:824	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	83	from	mono-	844:848	arg1	O-glycans					816:824	N-acetylglucosamine linked O-glycans	789:824	N-acetylglucosamine linked O-glycans	789:824	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	83	from	mono-	844:848	arg1	range					833:837	the range	829:837	the range from mono- to hexasaccharides	829:867	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	83	from	mono-	844:848	arg1	rhamnose-					775:783	hitherto undescribed rhamnose-	754:783	hitherto undescribed rhamnose-	754:783	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	0	84	theme	Rhamnose	136:143	arg1	Rearrangement					154:166	Rhamnose Fragment Rearrangement	136:166	Rhamnose Fragment Rearrangement	136:166	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides.
29339411	10	85	gly	glycosylated	1877:1888	arg1	site					1868:1871	just a single site	1854:1871	just a single site	1854:1871	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	9	86	theme	additional	1720:1729	arg1	sites					1745:1749	additional glycosylation sites	1720:1749	additional glycosylation sites	1720:1749	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	7	87	theme	native	1463:1468	arg1	flagellin					1483:1491	native S. sputigena flagellin	1463:1491	native S. sputigena flagellin	1463:1491	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	14	88	with	ProteomeXchange	2432:2446	arg1	identifier					2453:2462	identifier PXD005859	2453:2472	identifier PXD005859	2453:2472	The data have been deposited to the ProteomeXchange with identifier PXD005859.
29339411	2	89	theme	periodontal	434:444	arg1	pathogen					446:453	a potential human periodontal pathogen	416:453	a potential human periodontal pathogen	416:453	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	5	90	theme	only	1193:1196	arg1	protein					1208:1214	the only flagellin protein	1189:1214	the only flagellin protein identified	1189:1225	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	90	theme	only	1193:1196	arg1	protein					1135:1141	the 437-amino acid C9LY14 protein	1109:1141	the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334)	1109:1186	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	9	91	theme	sites	1745:1749	arg1	presence					1708:1715	the presence	1704:1715	the presence of additional glycosylation sites on a single glycopeptide	1704:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	1	92	dep	Flagellated	200:210	arg1	crescent-shaped					239:253	crescent-shaped	239:253	crescent-shaped	239:253	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	1	92	dep	Flagellated	200:210	arg1	anaerobic					228:236	anaerobic	228:236	anaerobic	228:236	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	1	92	dep	Flagellated	200:210	arg1	Gram-negative					213:225	Gram-negative	213:225	Gram-negative	213:225	Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are colonizers of the digestive system, where they act at the interface between health and disease.
29339411	2	93	theme	potential	418:426	arg1	pathogen					446:453	a potential human periodontal pathogen	416:453	a potential human periodontal pathogen	416:453	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	0	94	dep	Reveals	89:95	arg1	Described					112:120	Described	112:120	Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides	89:197	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides.
29339411	9	95	gly	glycosylation	1731:1743	arg2	sites					1745:1749	additional glycosylation sites	1720:1749	additional glycosylation sites	1720:1749	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	3	96	theme	first	568:572	arg1	report					574:579	the first report	564:579	the first report of a Selenomonas glycoprotein	564:609	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	0	97	theme	Associated	47:56	arg1	Pathogen					58:65	the Periodontitis Associated Pathogen	29:65	the Periodontitis Associated Pathogen	29:65	Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment Rearrangement Occurring on the Glycopeptides.
29339411	10	98	theme	glycan	2029:2034	arg1	moiety					2036:2041	the glycan moiety	2025:2041	the glycan moiety	2025:2041	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	7	99	theme	m/z	1418:1420	arg1	values					1422:1427	their respective m/z values	1401:1427	their respective m/z values	1401:1427	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	2	100	theme	underlying	501:510	arg1	mechanisms					526:535	underlying pathogenicity mechanisms	501:535	underlying pathogenicity mechanisms	501:535	Selenomonas sputigena is also considered a potential human periodontal pathogen, but information on its virulence factors and underlying pathogenicity mechanisms is scarce.
29339411	3	101	dep	linked	809:814	arg1	N-acetylglucosamine					789:807	N-acetylglucosamine	789:807	N-acetylglucosamine	789:807	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	102	theme	cellular	714:721	arg1	protein					723:729	a major cellular protein	706:729	a major cellular protein	706:729	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	3	102	theme	cellular	714:721	arg1	C9LY14					696:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	a diversely and heavily O-glycosylated flagellin C9LY14	647:701	Here we provide the first report of a Selenomonas glycoprotein, showing that S. sputigena produces a diversely and heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O-glycans in the range from mono- to hexasaccharides.
29339411	7	103	contain	carried	1332:1338	arg2	residues/modifications					1361:1382	hitherto undescribed residues/modifications	1340:1382	hitherto undescribed residues/modifications	1340:1382	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	7	103	contain	carried	1332:1338	arg1	O-glycans					1322:1330	Some O-glycans	1317:1330	Some O-glycans	1317:1330	Some O-glycans carried hitherto undescribed residues/modifications as determined by their respective m/z values, reflecting the high diversity of native S. sputigena flagellin.
29339411	10	104	theme	single	1861:1866	arg1	site					1868:1871	just a single site	1854:1871	just a single site	1854:1871	CID oxonium ions and electron transfer dissociation, however, confirmed that just a single site was glycosylated, showing that glycan-to-peptide rearrangement can occur on glycopeptides and that this effect is influenced by the molecular nature of the glycan moiety.
29339411	13	105	theme	properties	2367:2376	arg1	understanding					2311:2323	our understanding	2307:2323	our understanding of the largely under-investigated surface properties of oral bacteria	2307:2393	This study contributes to our understanding of the largely under-investigated surface properties of oral bacteria.
29339411	5	106	theme	acid	1123:1126	arg1	protein					1208:1214	the only flagellin protein	1189:1214	the only flagellin protein identified	1189:1225	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	5	106	theme	acid	1123:1126	arg1	protein					1135:1141	the 437-amino acid C9LY14 protein	1109:1141	the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334)	1109:1186	From the multiple sites of glycosylation, five were unambiguously identified on the 437-amino acid C9LY14 protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein identified.
29339411	9	107	attach	presence	1708:1715	arg1	glycopeptide					1763:1774	a single glycopeptide	1754:1774	a single glycopeptide	1754:1774	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	9	107	attach	presence	1708:1715	arg2	sites					1745:1749	additional glycosylation sites	1720:1749	additional glycosylation sites	1720:1749	This effect resulted in pseudo Y1-glycopeptide fragment ions that indicated the presence of additional glycosylation sites on a single glycopeptide.
29339411	4	108	theme	comprehensive	872:884	arg1	assessment					914:923	A comprehensive glycomic and glycoproteomic assessment	870:923	A comprehensive glycomic and glycoproteomic assessment	870:923	A comprehensive glycomic and glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity identified from 22 unique glycopeptide species.
29339411	13	109	theme	oral	2381:2384	arg1	bacteria					2386:2393	oral bacteria	2381:2393	oral bacteria	2381:2393	This study contributes to our understanding of the largely under-investigated surface properties of oral bacteria.
29969454	7	0	theme	varying	1248:1254	arg1	levels					1256:1261	varying levels	1248:1261	varying levels of infection and airborne transmission	1248:1300	Additionally, the isolates also showed varying levels of infection and airborne transmission.
29969454	1	1	theme	avian	135:139	arg1	viruses					151:157	the H9N2 avian influenza viruses	126:157	the H9N2 avian influenza viruses	126:157	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	7	2	theme	airborne	1280:1287	arg1	transmission					1289:1300	airborne transmission	1280:1300	airborne transmission	1280:1300	Additionally, the isolates also showed varying levels of infection and airborne transmission.
29969454	2	3	theme	poultry	417:423	arg1	markets					425:431	live poultry markets	412:431	live poultry markets in China	412:440	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	5	4	theme	avian	952:956	arg1	H10N8					992:996	H10N8	992:996	H10N8	992:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	4	theme	avian	952:956	arg1	H5N1					976:979	H5N1	976:979	H5N1	976:979	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	4	theme	avian	952:956	arg1	viruses					968:974	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	4	theme	avian	952:956	arg1	H7N9					982:985	H7N9	982:985	H7N9	982:985	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	1	5	theme	influenza	141:149	arg1	viruses					151:157	the H9N2 avian influenza viruses	126:157	the H9N2 avian influenza viruses	126:157	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	6	6	dep	H9N2	1164:1167	arg1	viruses					1186:1192	viruses	1186:1192	viruses	1186:1192	In particular, the NS gene in the phylogenetic tree revealed genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively.
29969454	3	7	theme	potential	587:595	arg1	sites					620:624	two potential N-linked glycosylation sites	583:624	two potential N-linked glycosylation sites	583:624	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	1	8	theme	gene	301:304	arg1	lineage					285:291	the fittest lineage	273:291	the fittest lineage of each gene	273:304	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	6	9	theme	phylogenetic	1033:1044	arg1	tree					1046:1049	the phylogenetic tree	1029:1049	the phylogenetic tree	1029:1049	In particular, the NS gene in the phylogenetic tree revealed genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively.
29969454	6	10	theme	virus	1086:1090	arg1	gene					1092:1095	the virus gene	1082:1095	the virus gene	1082:1095	In particular, the NS gene in the phylogenetic tree revealed genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively.
29969454	3	11	link	N-linked	597:604	arg1	sites					620:624	two potential N-linked glycosylation sites	583:624	two potential N-linked glycosylation sites	583:624	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	3	12	theme	binding	662:668	arg1	protein					685:691	the HA protein	678:691	the HA protein	678:691	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	3	12	theme	binding	662:668	arg1	site					670:673	the receptor binding site	649:673	the receptor binding site of the HA protein	649:691	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	7	13	theme	transmission	1289:1300	arg1	levels					1256:1261	varying levels	1248:1261	varying levels of infection and airborne transmission	1248:1300	Additionally, the isolates also showed varying levels of infection and airborne transmission.
29969454	2	14	attach	isolated	398:405	arg1	2011-2014					447:455	2011-2014	447:455	2011-2014	447:455	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	2	14	attach	isolated	398:405	arg2	viruses					385:391	28 H9N2 influenza viruses	367:391	28 H9N2 influenza viruses	367:391	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	2	14	attach	isolated	398:405	arg1	markets					425:431	live poultry markets	412:431	live poultry markets in China	412:440	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	1	15	theme	viruses	151:157	arg1	genotypes					113:121	The genotypes	109:121	The genotypes of the H9N2 avian influenza viruses	109:157	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	7	16	theme	infection	1266:1274	arg1	levels					1256:1261	varying levels	1248:1261	varying levels of infection and airborne transmission	1248:1300	Additionally, the isolates also showed varying levels of infection and airborne transmission.
29969454	2	17	theme	live	412:415	arg1	markets					425:431	live poultry markets	412:431	live poultry markets in China	412:440	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	0	18	theme	Genetic	0:6	arg1	characterization					23:38	Genetic and biological characterization	0:38	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.	0:107	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	3	19	theme	receptor	653:660	arg1	protein					685:691	the HA protein	678:691	the HA protein	678:691	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	3	19	theme	receptor	653:660	arg1	site					670:673	the receptor binding site	649:673	the receptor binding site of the HA protein	649:691	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	2	20	theme	variant	332:338	arg1	viruses					340:346	the H9N2 variant viruses	323:346	the H9N2 variant viruses from 2011 to 2014	323:364	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	2	21	theme	influenza	375:383	arg1	viruses					385:391	28 H9N2 influenza viruses	367:391	28 H9N2 influenza viruses	367:391	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	3	22	theme	HA	682:683	arg1	protein					685:691	the HA protein	678:691	the HA protein	678:691	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	4	23	theme	phylogenetic	768:779	arg1	tree					781:784	the phylogenetic tree	764:784	the phylogenetic tree	764:784	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	1	24	with	genotype	250:257	arg1	lineage					285:291	the fittest lineage	273:291	the fittest lineage of each gene	273:304	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	6	25	from	gene	1021:1024	arg1	tree					1046:1049	the phylogenetic tree	1029:1049	the phylogenetic tree	1029:1049	In particular, the NS gene in the phylogenetic tree revealed genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively.
29969454	2	26	theme	H9N2	327:330	arg1	viruses					340:346	the H9N2 variant viruses	323:346	the H9N2 variant viruses from 2011 to 2014	323:364	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	2	27	theme	H9N2	370:373	arg1	viruses					385:391	28 H9N2 influenza viruses	367:391	28 H9N2 influenza viruses	367:391	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	3	28	theme	protein	685:691	arg1	protein					685:691	the HA protein	678:691	the HA protein	678:691	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	3	28	theme	protein	685:691	arg1	site					670:673	the receptor binding site	649:673	the receptor binding site of the HA protein	649:691	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	6	29	theme	gene	1092:1095	arg1	divergence					1068:1077	genetic divergence	1060:1077	genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively	1060:1206	In particular, the NS gene in the phylogenetic tree revealed genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively.
29969454	0	30	theme	biological	12:21	arg1	characterization					23:38	Genetic and biological characterization	0:38	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.	0:107	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	6	31	theme	genetic	1060:1066	arg1	divergence					1068:1077	genetic divergence	1060:1077	genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively	1060:1206	In particular, the NS gene in the phylogenetic tree revealed genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively.
29969454	2	32	theme	genetic	478:484	arg1	characterization					501:516	genetic and biological characterization	478:516	genetic and biological characterization	478:516	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	2	33	from	markets	425:431	arg1	China					436:440	China	436:440	China	436:440	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	6	34	theme	NS	1018:1019	arg1	gene					1021:1024	the NS gene	1014:1024	the NS gene in the phylogenetic tree	1014:1049	In particular, the NS gene in the phylogenetic tree revealed genetic divergence of the virus gene into three branches labeled A, B, and C, which were related to the H9N2, H10N8, and H7N9 viruses, respectively.
29969454	8	35	theme	adaptive	1364:1371	arg1	evolution					1373:1381	an adaptive evolution	1361:1381	an adaptive evolution	1361:1381	These results indicated that the H9N2 virus had undergone an adaptive evolution and variation from 2011-2014.
29969454	0	36	theme	H9N2	43:46	arg1	viruses					64:70	H9N2 avian influenza viruses	43:70	H9N2 avian influenza viruses	43:70	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	1	37	from	chickens	227:234	arg1	China					239:243	China	239:243	China	239:243	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	3	38	theme	N-linked	597:604	arg1	sites					620:624	two potential N-linked glycosylation sites	583:624	two potential N-linked glycosylation sites	583:624	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	4	39	theme	HA	745:746	arg1	genes					755:759	the HA and NA genes	741:759	the HA and NA genes in the phylogenetic tree	741:784	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	4	40	from	genes	755:759	arg1	tree					781:784	the phylogenetic tree	764:784	the phylogenetic tree	764:784	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	1	41	theme	all	195:197	arg1	viruses					204:210	almost all H9N2 viruses	188:210	almost all H9N2 viruses circulating in chickens in China	188:243	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	0	42	theme	influenza	54:62	arg1	viruses					64:70	H9N2 avian influenza viruses	43:70	H9N2 avian influenza viruses	43:70	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	4	43	theme	independent	817:827	arg1	branches					829:836	two independent branches	813:836	two independent branches	813:836	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	4	43	theme	independent	817:827	arg1	B					845:845	B	845:845	B	845:845	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	4	43	theme	independent	817:827	arg1	A					839:839	A	839:839	A	839:839	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	0	44	attach	isolated	72:79	arg1	2011					95:98	2011	95:98	2011 to 2014	95:106	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	0	44	attach	isolated	72:79	arg2	characterization					23:38	Genetic and biological characterization	0:38	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.	0:107	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	8	45	theme	H9N2	1336:1339	arg1	virus					1341:1345	the H9N2 virus	1332:1345	the H9N2 virus	1332:1345	These results indicated that the H9N2 virus had undergone an adaptive evolution and variation from 2011-2014.
29969454	0	46	theme	avian	48:52	arg1	viruses					64:70	H9N2 avian influenza viruses	43:70	H9N2 avian influenza viruses	43:70	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	4	47	theme	NA	752:753	arg1	genes					755:759	the HA and NA genes	741:759	the HA and NA genes in the phylogenetic tree	741:784	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	1	48	theme	fittest	277:283	arg1	lineage					285:291	the fittest lineage	273:291	the fittest lineage of each gene	273:304	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	5	49	theme	human-infected	937:950	arg1	H10N8					992:996	H10N8	992:996	H10N8	992:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	49	theme	human-infected	937:950	arg1	H5N1					976:979	H5N1	976:979	H5N1	976:979	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	49	theme	human-infected	937:950	arg1	viruses					968:974	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	49	theme	human-infected	937:950	arg1	H7N9					982:985	H7N9	982:985	H7N9	982:985	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	50	theme	virus	885:889	arg1	genes					900:904	H9N2 virus internal genes	880:904	H9N2 virus internal genes	880:904	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	1	51	theme	H9N2	199:202	arg1	viruses					204:210	almost all H9N2 viruses	188:210	almost all H9N2 viruses circulating in chickens in China	188:243	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	2	52	theme	biological	490:499	arg1	characterization					501:516	genetic and biological characterization	478:516	genetic and biological characterization	478:516	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	3	53	theme	glycosylation	606:618	arg1	sites					620:624	two potential N-linked glycosylation sites	583:624	two potential N-linked glycosylation sites	583:624	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	5	54	theme	internal	891:898	arg1	genes					900:904	H9N2 virus internal genes	880:904	H9N2 virus internal genes	880:904	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	55	theme	H9N2	880:883	arg1	genes					900:904	H9N2 virus internal genes	880:904	H9N2 virus internal genes	880:904	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	4	56	theme	isolation	869:877	arg1	year					861:864	the year	857:864	the year of isolation	857:877	Moreover, the HA and NA genes in the phylogenetic tree were mainly clustered into two independent branches, A and B, based on the year of isolation.
29969454	5	57	theme	influenza	958:966	arg1	H10N8					992:996	H10N8	992:996	H10N8	992:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	57	theme	influenza	958:966	arg1	H5N1					976:979	H5N1	976:979	H5N1	976:979	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	57	theme	influenza	958:966	arg1	viruses					968:974	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	57	theme	influenza	958:966	arg1	H7N9					982:985	H7N9	982:985	H7N9	982:985	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	3	58	theme	amino	635:639	arg1	acid					641:644	one amino acid	631:644	one amino acid	631:644	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	2	59	from	2011	353:356	arg1	viruses					340:346	the H9N2 variant viruses	323:346	the H9N2 variant viruses from 2011 to 2014	323:364	To characterize the H9N2 variant viruses from 2011 to 2014, 28 H9N2 influenza viruses were isolated from live poultry markets in China from 2011-2014 and were analyzed by genetic and biological characterization.
29969454	5	60	dep	viruses	968:974	arg1	H10N8					992:996	H10N8	992:996	H10N8	992:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	60	dep	viruses	968:974	arg1	H5N1					976:979	H5N1	976:979	H5N1	976:979	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	60	dep	viruses	968:974	arg1	viruses					968:974	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	the human-infected avian influenza viruses H5N1, H7N9, and H10N8	933:996	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	5	60	dep	viruses	968:974	arg1	H7N9					982:985	H7N9	982:985	H7N9	982:985	H9N2 virus internal genes were related to those from the human-infected avian influenza viruses H5N1, H7N9, and H10N8.
29969454	0	61	theme	viruses	64:70	arg1	characterization					23:38	Genetic and biological characterization	0:38	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.	0:107	Genetic and biological characterization of H9N2 avian influenza viruses isolated in China from 2011 to 2014.
29969454	1	62	theme	H9N2	130:133	arg1	viruses					151:157	the H9N2 avian influenza viruses	126:157	the H9N2 avian influenza viruses	126:157	The genotypes of the H9N2 avian influenza viruses have changed since 2013 when almost all H9N2 viruses circulating in chickens in China were genotype 57 (G57) with the fittest lineage of each gene.
29969454	3	63	gly	glycosylation	606:618	arg2	sites					620:624	two potential N-linked glycosylation sites	583:624	two potential N-linked glycosylation sites	583:624	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29969454	3	63	gly	glycosylation	606:618	arg2	two					583:585	two	583:585	two	583:585	Our findings showed that 16 residues that changed antigenicity, two potential N-linked glycosylation sites, and one amino acid in the receptor binding site of the HA protein changed significantly from 2011-2014.
29267884	2	0	theme	features	379:386	arg1	number					360:365	a number	358:365	a number	358:365	We present a version 2.0 of GlycoDomainViewer incorporating a number of advanced features, which enhances visibility and accessibility of the wealth of glycoproteomic data being generated.
29267884	1	1	theme	protein	266:272	arg1	structure					274:282	protein structure	266:282	protein structure	266:282	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	1	2	theme	glycoproteomic	157:170	arg1	datasets					172:179	glycoproteomic datasets	157:179	glycoproteomic datasets from different sources	157:202	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	1	3	theme	structure	274:282	arg1	studies					255:261	studies	255:261	studies of protein structure and function	255:295	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	5	4	gly	glycosylation	946:958	arg2	sites					960:964	known glycosylation sites	940:964	known glycosylation sites	940:964	The data made available via this tool will be regularly updated to improve the coverage of known glycosylation sites and datasets, reflecting the advances currently being made in characterization of glycoproteomes.
29267884	2	5	theme	advanced	370:377	arg1	features					379:386	advanced features	370:386	advanced features	370:386	We present a version 2.0 of GlycoDomainViewer incorporating a number of advanced features, which enhances visibility and accessibility of the wealth of glycoproteomic data being generated.
29267884	3	6	theme	N-	598:599	arg1	studies					621:627	recent N- and O-glycoproteome studies	591:627	recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids	591:690	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	6	7	from	//glycodomain.glycomics.ku.dk	1095:1123	arg1	tool					1068:1071	The tool	1064:1071	The tool	1064:1071	The tool is available at https://glycodomain.glycomics.ku.dk.
29267884	6	7	from	//glycodomain.glycomics.ku.dk	1095:1123	arg1	available					1076:1084	available	1076:1084	available	1076:1084	The tool is available at https://glycodomain.glycomics.ku.dk.
29267884	5	8	theme	known	940:944	arg1	sites					960:964	known glycosylation sites	940:964	known glycosylation sites	940:964	The data made available via this tool will be regularly updated to improve the coverage of known glycosylation sites and datasets, reflecting the advances currently being made in characterization of glycoproteomes.
29267884	3	9	theme	data	554:557	arg1	exploration					524:534	visual exploration	517:534	visual exploration of glycoproteomic data	517:557	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	1	10	theme	function	288:295	arg1	studies					255:261	studies	255:261	studies of protein structure and function	255:295	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	1	11	from	mining	147:152	arg1	sources					196:202	different sources	186:202	different sources	186:202	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	1	12	theme	datasets	172:179	arg1	mining					147:152	the mining	143:152	the mining of glycoproteomic datasets from different sources	143:202	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	3	13	theme	recent	591:596	arg1	studies					621:627	recent N- and O-glycoproteome studies	591:627	recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids	591:690	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	4	14	theme	initial	697:703	arg1	data					705:708	The initial data	693:708	The initial data	693:708	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	2	15	theme	GlycoDomainViewer	326:342	arg1	version					311:317	a version 2.0	309:321	a version 2.0 of GlycoDomainViewer	309:342	We present a version 2.0 of GlycoDomainViewer incorporating a number of advanced features, which enhances visibility and accessibility of the wealth of glycoproteomic data being generated.
29267884	1	16	theme	different	186:194	arg1	sources					196:202	different sources	186:202	different sources	186:202	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	3	17	theme	human	632:636	arg1	lines					654:658	cell lines	649:658	cell lines	649:658	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	2	18	theme	data	465:468	arg1	wealth					440:445	the wealth	436:445	the wealth of glycoproteomic data	436:468	We present a version 2.0 of GlycoDomainViewer incorporating a number of advanced features, which enhances visibility and accessibility of the wealth of glycoproteomic data being generated.
29267884	5	19	theme	glycoproteomes	1048:1061	arg1	characterization					1028:1043	characterization	1028:1043	characterization of glycoproteomes	1028:1061	The data made available via this tool will be regularly updated to improve the coverage of known glycosylation sites and datasets, reflecting the advances currently being made in characterization of glycoproteomes.
29267884	3	20	theme	O-glycoproteome	605:619	arg1	studies					621:627	recent N- and O-glycoproteome studies	591:627	recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids	591:690	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	4	21	theme	O-GlcNAc	834:841	arg1	type					843:846	O-GlcNAc type	834:846	O-GlcNAc type	834:846	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	5	22	theme	datasets	970:977	arg1	coverage					928:935	the coverage	924:935	the coverage of known glycosylation sites and datasets	924:977	The data made available via this tool will be regularly updated to improve the coverage of known glycosylation sites and datasets, reflecting the advances currently being made in characterization of glycoproteomes.
29267884	2	23	theme	glycoproteomic	450:463	arg1	data					465:468	glycoproteomic data	450:468	glycoproteomic data	450:468	We present a version 2.0 of GlycoDomainViewer incorporating a number of advanced features, which enhances visibility and accessibility of the wealth of glycoproteomic data being generated.
29267884	5	24	theme	glycosylation	946:958	arg1	sites					960:964	known glycosylation sites	940:964	known glycosylation sites	940:964	The data made available via this tool will be regularly updated to improve the coverage of known glycosylation sites and datasets, reflecting the advances currently being made in characterization of glycoproteomes.
29267884	5	25	theme	sites	960:964	arg1	coverage					928:935	the coverage	924:935	the coverage of known glycosylation sites and datasets	924:977	The data made available via this tool will be regularly updated to improve the coverage of known glycosylation sites and datasets, reflecting the advances currently being made in characterization of glycoproteomes.
29267884	1	26	theme	bioinformatic	114:126	arg1	tool					128:131	a bioinformatic tool	112:131	a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function	112:295	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	1	26	theme	bioinformatic	114:126	arg1	GlycoDomainViewer					91:107	The GlycoDomainViewer	87:107	The GlycoDomainViewer	87:107	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	3	27	theme	cell	649:652	arg1	lines					654:658	cell lines	649:658	cell lines	649:658	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	3	28	theme	body	680:683	arg1	fluids					685:690	body fluids	680:690	body fluids	680:690	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	0	29	theme	bioinformatics	21:34	arg1	tool					36:39	a bioinformatics tool	19:39	GlycoDomainViewer: a bioinformatics tool for contextual exploration of glycoproteomes.	0:85	GlycoDomainViewer: a bioinformatics tool for contextual exploration of glycoproteomes.
29267884	4	30	dep	O-Mannose	784:792	arg1	yeast					813:817	yeast	813:817	yeast	813:817	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	4	30	dep	O-Mannose	784:792	arg1	human					803:807	human	803:807	human	803:807	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	0	31	theme	contextual	45:54	arg1	exploration					56:66	contextual exploration	45:66	contextual exploration of glycoproteomes	45:84	GlycoDomainViewer: a bioinformatics tool for contextual exploration of glycoproteomes.
29267884	4	32	gly	glycosylation	729:741	arg2	sites					720:724	sites	720:724	sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type	720:846	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	4	32	gly	glycosylation	729:741	arg2	glycosylation					729:741	glycosylation	729:741	glycosylation	729:741	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	3	33	theme	animal	642:647	arg1	lines					654:658	cell lines	649:658	cell lines	649:658	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	3	34	theme	glycoproteomic	539:552	arg1	data					554:557	glycoproteomic data	539:557	glycoproteomic data	539:557	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	3	35	theme	visual	517:522	arg1	exploration					524:534	visual exploration	517:534	visual exploration of glycoproteomic data	517:557	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	3	36	from	studies	621:627	arg1	lines					654:658	cell lines	649:658	cell lines	649:658	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	3	36	from	studies	621:627	arg1	organs					669:674	organs	669:674	organs	669:674	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	3	36	from	studies	621:627	arg1	information					574:584	information	574:584	information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids	574:690	The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body fluids.
29267884	1	37	theme	glycosylation	236:248	arg1	incorporation					219:231	incorporation	219:231	incorporation of glycosylation into studies of protein structure and function	219:295	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	4	38	dep	N-linked	747:754	arg1	type					843:846	O-GlcNAc type	834:846	O-GlcNAc type	834:846	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	0	39	theme	glycoproteomes	71:84	arg1	exploration					56:66	contextual exploration	45:66	contextual exploration of glycoproteomes	45:84	GlycoDomainViewer: a bioinformatics tool for contextual exploration of glycoproteomes.
29267884	1	40	from	sources	196:202	arg1	mining					147:152	the mining	143:152	the mining of glycoproteomic datasets from different sources	143:202	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	1	40	from	sources	196:202	arg1	datasets					172:179	glycoproteomic datasets	157:179	glycoproteomic datasets from different sources	157:202	The GlycoDomainViewer is a bioinformatic tool to aid in the mining of glycoproteomic datasets from different sources and facilitate incorporation of glycosylation into studies of protein structure and function.
29267884	4	41	theme	glycosylation	729:741	arg1	glycosylation					729:741	glycosylation	729:741	glycosylation	729:741	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	4	41	theme	glycosylation	729:741	arg1	sites					720:724	sites	720:724	sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type	720:846	The initial data comprises sites of glycosylation for N-linked, O-GalNAc, O-Fucose, O-Xyl, O-Mannose (in both human and yeast) and cytosolic O-GlcNAc type.
29267884	6	42	theme	https	1089:1093	arg1	//glycodomain.glycomics.ku.dk					1095:1123	https://glycodomain.glycomics.ku.dk	1089:1123	https://glycodomain.glycomics.ku.dk	1089:1123	The tool is available at https://glycodomain.glycomics.ku.dk.
29267884	0	43	dep	GlycoDomainViewer	0:16	arg1	tool					36:39	a bioinformatics tool	19:39	GlycoDomainViewer: a bioinformatics tool for contextual exploration of glycoproteomes.	0:85	GlycoDomainViewer: a bioinformatics tool for contextual exploration of glycoproteomes.
30100348	8	0	dep	detection	1041:1049	arg1	The					1037:1039	The	1037:1039	The	1037:1039	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	6	1	theme	HEK	908:910	arg1	cells					912:916	HEK cells	908:916	HEK cells	908:916	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	7	2	theme	O-GlcNAc	972:979	arg1	degree					962:967	the modification degree	945:967	the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells	945:1020	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	6	3	theme	cellular	887:894	arg1	AKT1					865:868	AKT1	865:868	AKT1	865:868	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	3	theme	cellular	887:894	arg1	PFKFB3					875:880	PFKFB3	875:880	PFKFB3	875:880	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	3	theme	cellular	887:894	arg1	CK2					860:862	CK2	860:862	CK2	860:862	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	3	theme	cellular	887:894	arg1	extracts					896:903	cellular extracts	887:903	cellular extracts of HEK cells	887:916	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	4	theme	purified	820:827	arg1	AKT1					865:868	AKT1	865:868	AKT1	865:868	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	4	theme	purified	820:827	arg1	PFKFB3					875:880	PFKFB3	875:880	PFKFB3	875:880	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	4	theme	purified	820:827	arg1	CK2					860:862	CK2	860:862	CK2	860:862	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	4	theme	purified	820:827	arg1	proteins					841:848	purified recombinant proteins	820:848	purified recombinant proteins including CK2, AKT1, and PFKFB3	820:880	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	1	5	theme	protein	184:190	arg1	activity					192:199	protein activity	184:199	protein activity	184:199	O-GlcNAcylation is a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells.
30100348	4	6	theme	in vitro	517:524	arg1	incorporation					526:538	in vitro incorporation	517:538	in vitro incorporation of GalNAz by B3GALNT2	517:560	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	4	7	theme	in vitro	594:601	arg1	incorporation					603:615	in vitro incorporation	594:615	in vitro incorporation of GlcNAz	594:625	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	0	8	theme	Study	90:94	arg1	O-GlcNAc					96:103	Study O-GlcNAc	90:103	Study O-GlcNAc	90:103	Detecting and Imaging O-GlcNAc Sites Using Glycosyltransferases: A Systematic Approach to Study O-GlcNAc.
30100348	4	9	theme	closed	485:490	arg1	sites					492:496	closed sites	485:496	closed sites	485:496	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	1	10	theme	serine/threonine	138:153	arg1	glycosylation					155:167	a reversible serine/threonine glycosylation	125:167	a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells	125:229	O-GlcNAcylation is a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells.
30100348	1	10	theme	serine/threonine	138:153	arg1	O-GlcNAcylation					106:120	O-GlcNAcylation	106:120	O-GlcNAcylation	106:120	O-GlcNAcylation is a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells.
30100348	8	11	theme	post-translational	1156:1173	arg1	modification					1175:1186	this important post-translational modification	1141:1186	this important post-translational modification	1141:1186	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	2	12	theme	O-GlcNAc	314:321	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	12	theme	O-GlcNAc	314:321	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	13	link	O-linked	282:289	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	13	link	O-linked	282:289	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	7	14	theme	O-GlcNAc	927:934	arg1	imaging					936:942	O-GlcNAc imaging	927:942	O-GlcNAc imaging	927:942	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	3	15	theme	open	406:409	arg1	sites					422:426	open and closed sites	406:426	open and closed sites	406:426	The balance between open and closed sites is believed to be dynamically regulated.
30100348	8	16	theme	systematic	1112:1121	arg1	approach					1123:1130	a systematic approach	1110:1130	a systematic approach to study this important post-translational modification	1110:1186	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	4	17	theme	click	662:666	arg1	chemistry					668:676	click chemistry	662:676	click chemistry	662:676	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	0	18	theme	Detecting	0:8	arg1	Sites					31:35	Detecting and Imaging O-GlcNAc Sites	0:35	Detecting and Imaging O-GlcNAc Sites	0:35	Detecting and Imaging O-GlcNAc Sites Using Glycosyltransferases: A Systematic Approach to Study O-GlcNAc.
30100348	0	19	theme	O-GlcNAc	22:29	arg1	Sites					31:35	Detecting and Imaging O-GlcNAc Sites	0:35	Detecting and Imaging O-GlcNAc Sites	0:35	Detecting and Imaging O-GlcNAc Sites Using Glycosyltransferases: A Systematic Approach to Study O-GlcNAc.
30100348	5	20	theme	total O-GlcNAc	693:706	arg1	sites					708:712	total O-GlcNAc sites	693:712	total O-GlcNAc sites	693:712	For assessing total O-GlcNAc sites, a sample is O-GlcNAcylated in vitro by OGT before detecting by B3GALNT2.
30100348	7	21	theme	modification	949:960	arg1	degree					962:967	the modification degree	945:967	the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells	945:1020	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	0	22	theme	Imaging	14:20	arg1	Sites					31:35	Detecting and Imaging O-GlcNAc Sites	0:35	Detecting and Imaging O-GlcNAc Sites	0:35	Detecting and Imaging O-GlcNAc Sites Using Glycosyltransferases: A Systematic Approach to Study O-GlcNAc.
30100348	7	23	from	degree	962:967	arg1	nuclei					984:989	nuclei	984:989	nuclei of Chinese hamster ovary cells	984:1020	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	4	24	theme	O-GlcNAc	630:637	arg1	OGT					652:654	OGT	652:654	OGT	652:654	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	4	24	theme	O-GlcNAc	630:637	arg1	transferase					639:649	O-GlcNAc transferase	630:649	O-GlcNAc transferase (OGT)	630:655	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	4	25	theme	open	567:570	arg1	sites					572:576	open sites	567:576	open sites	567:576	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	2	26	theme	O-GlcNAcylated	252:265	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	26	theme	O-GlcNAcylated	252:265	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	4	27	theme	GalNAz	543:548	arg1	incorporation					526:538	in vitro incorporation	517:538	in vitro incorporation of GalNAz by B3GALNT2	517:560	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	8	28	theme	open	1071:1074	arg1	sites					1096:1100	both open and closed O-GlcNAc sites	1066:1100	both open and closed O-GlcNAc sites	1066:1100	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	7	29	theme	hamster	1002:1008	arg1	cells					1016:1020	Chinese hamster ovary cells	994:1020	Chinese hamster ovary cells	994:1020	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	8	30	theme	important	1146:1154	arg1	modification					1175:1186	this important post-translational modification	1141:1186	this important post-translational modification	1141:1186	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	3	31	theme	closed	415:420	arg1	sites					422:426	open and closed sites	406:426	open and closed sites	406:426	The balance between open and closed sites is believed to be dynamically regulated.
30100348	8	32	theme	O-GlcNAc	1087:1094	arg1	sites					1096:1100	both open and closed O-GlcNAc sites	1066:1100	both open and closed O-GlcNAc sites	1066:1100	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	0	33	dep	Using	37:41	arg1	Approach					78:85	A Systematic Approach	65:85	A Systematic Approach to Study O-GlcNAc	65:103	Detecting and Imaging O-GlcNAc Sites Using Glycosyltransferases: A Systematic Approach to Study O-GlcNAc.
30100348	7	34	theme	ovary	1010:1014	arg1	cells					1016:1020	Chinese hamster ovary cells	994:1020	Chinese hamster ovary cells	994:1020	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	4	35	located	detected	502:509	arg2	sites					492:496	closed sites	485:496	closed sites	485:496	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	4	35	located	detected	502:509	arg1	report					477:482	this report	472:482	this report	472:482	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
30100348	8	36	theme	closed	1080:1085	arg1	sites					1096:1100	both open and closed O-GlcNAc sites	1066:1100	both open and closed O-GlcNAc sites	1066:1100	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	2	37	theme	given	237:241	arg1	protein					243:249	a given protein	235:249	a given protein	235:249	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	38	theme	open	360:363	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	38	theme	open	360:363	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	7	39	theme	cells	1016:1020	arg1	nuclei					984:989	nuclei	984:989	nuclei of Chinese hamster ovary cells	984:1020	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	2	40	theme	β-N-acetylglucosamine	291:311	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	40	theme	β-N-acetylglucosamine	291:311	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	7	41	theme	Chinese	994:1000	arg1	cells					1016:1020	Chinese hamster ovary cells	994:1020	Chinese hamster ovary cells	994:1020	Through O-GlcNAc imaging, the modification degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated.
30100348	1	42	theme	reversible	127:136	arg1	glycosylation					155:167	a reversible serine/threonine glycosylation	125:167	a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells	125:229	O-GlcNAcylation is a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells.
30100348	1	42	theme	reversible	127:136	arg1	O-GlcNAcylation					106:120	O-GlcNAcylation	106:120	O-GlcNAcylation	106:120	O-GlcNAcylation is a reversible serine/threonine glycosylation for regulating protein activity and availability inside cells.
30100348	8	43	theme	sites	1096:1100	arg1	detection					1041:1049	detection	1041:1049	detection	1041:1049	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	8	43	theme	sites	1096:1100	arg1	imaging					1055:1061	imaging	1055:1061	imaging	1055:1061	The detection and imaging of both open and closed O-GlcNAc sites provide a systematic approach to study this important post-translational modification.
30100348	2	44	theme	O-linked	282:289	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	44	theme	O-linked	282:289	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	45	theme	closed	349:354	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	45	theme	closed	349:354	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	0	46	theme	Systematic	67:76	arg1	Approach					78:85	A Systematic Approach	65:85	A Systematic Approach to Study O-GlcNAc	65:103	Detecting and Imaging O-GlcNAc Sites Using Glycosyltransferases: A Systematic Approach to Study O-GlcNAc.
30100348	6	47	theme	recombinant	829:839	arg1	AKT1					865:868	AKT1	865:868	AKT1	865:868	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	47	theme	recombinant	829:839	arg1	PFKFB3					875:880	PFKFB3	875:880	PFKFB3	875:880	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	47	theme	recombinant	829:839	arg1	CK2					860:862	CK2	860:862	CK2	860:862	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	47	theme	recombinant	829:839	arg1	proteins					841:848	purified recombinant proteins	820:848	purified recombinant proteins including CK2, AKT1, and PFKFB3	820:880	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	2	48	theme	unoccupied	271:280	arg1	sites					324:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites	252:328	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	2	48	theme	unoccupied	271:280	arg1	sites					365:369	closed and open sites	349:369	closed and open sites	349:369	In a given protein, O-GlcNAcylated and unoccupied O-linked β-N-acetylglucosamine (O-GlcNAc) sites are referred to as closed and open sites, respectively.
30100348	6	49	theme	cells	912:916	arg1	AKT1					865:868	AKT1	865:868	AKT1	865:868	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	49	theme	cells	912:916	arg1	PFKFB3					875:880	PFKFB3	875:880	PFKFB3	875:880	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	49	theme	cells	912:916	arg1	CK2					860:862	CK2	860:862	CK2	860:862	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	49	theme	cells	912:916	arg1	proteins					841:848	purified recombinant proteins	820:848	purified recombinant proteins including CK2, AKT1, and PFKFB3	820:880	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	6	49	theme	cells	912:916	arg1	extracts					896:903	cellular extracts	887:903	cellular extracts of HEK cells	887:916	The methods are demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3, and cellular extracts of HEK cells.
30100348	4	50	theme	GlcNAz	620:625	arg1	incorporation					603:615	in vitro incorporation	594:615	in vitro incorporation of GlcNAz	594:625	In this report, closed sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase (OGT), via click chemistry.
28303575	4	0	theme	scanning	562:569	arg1	microscopy					571:580	confocal laser scanning microscopy	547:580	confocal laser scanning microscopy	547:580	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	8	1	theme	A.	1030:1031	arg1	quality					1043:1049	isoform A. Signaling quality	1022:1049	isoform A. Signaling quality	1022:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	5	2	theme	cytometric	675:684	arg1	array					691:695	cytometric bead array	675:695	cytometric bead array	675:695	Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively.
28303575	10	3	theme	cell	1267:1270	arg1	expression					1280:1289	its cell surface expression	1263:1289	its cell surface expression	1263:1289	We show here that n-glycosylation of Dectin-1 is crucial for its cell surface expression and consequently signal transduction.
28303575	3	4	link	monocyte-derived	400:415	arg1	cells					417:421	human monocyte-derived cells	394:421	human monocyte-derived cells	394:421	Here, we analyzed the expression of both isoforms in human monocyte-derived cells.
28303575	8	5	theme	quality	1043:1049	arg1	expression					1008:1017	cell surface expression	995:1017	cell surface expression of isoform A. Signaling quality	995:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	11	6	theme	type-specific	1500:1512	arg1	mechanism					1514:1522	a cell type-specific mechanism	1493:1522	a cell type-specific mechanism of regulating anti-fungal immunity	1493:1557	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	11	6	theme	type-specific	1500:1512	arg1	usage					1484:1488	distinct isoform usage	1467:1488	distinct isoform usage	1467:1488	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	10	7	gly	n-glycosylation	1220:1234	arg1	Dectin-1					1239:1246	Dectin-1	1239:1246	Dectin-1	1239:1246	We show here that n-glycosylation of Dectin-1 is crucial for its cell surface expression and consequently signal transduction.
28303575	7	8	theme	non-glycosylated	874:889	arg1	B					899:899	non-glycosylated isoform B	874:899	non-glycosylated isoform B	874:899	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	1	9	theme	anti-fungal	173:183	arg1	immunity					185:192	anti-fungal immunity	173:192	anti-fungal immunity	173:192	Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity.
28303575	8	10	theme	Dectin-1	1061:1068	arg1	stimulation					1070:1080	Dectin-1 stimulation	1061:1080	Dectin-1 stimulation	1061:1080	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	11	11	theme	monocyte-derived	1431:1446	arg1	cells					1448:1452	monocyte-derived cells	1431:1452	monocyte-derived cells	1431:1452	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	2	12	theme	region	297:302	arg1	presence					277:284	the presence	273:284	the presence of a stalk region and its N-linked glycosylation site	273:338	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	2	13	dep	isoforms	239:246	arg1	A					248:248	A	248:248	A	248:248	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	2	13	dep	isoforms	239:246	arg1	isoforms					239:246	Dectin-1 isoforms A and B	230:254	Dectin-1 isoforms A and B	230:254	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	2	13	dep	isoforms	239:246	arg1	B					254:254	B	254:254	B	254:254	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	11	14	theme	isoforms	1419:1426	arg1	levels					1394:1399	varying expression levels	1375:1399	varying expression levels	1375:1399	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	11	14	theme	isoforms	1419:1426	arg1	secretion					1361:1369	unique cytokine secretion	1345:1369	unique cytokine secretion	1345:1369	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	4	15	theme	cellular	428:435	arg1	localization					437:448	The cellular localization	424:448	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B	424:511	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	11	16	theme	distinct	1467:1474	arg1	mechanism					1514:1522	a cell type-specific mechanism	1493:1522	a cell type-specific mechanism of regulating anti-fungal immunity	1493:1557	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	11	16	theme	distinct	1467:1474	arg1	usage					1484:1488	distinct isoform usage	1467:1488	distinct isoform usage	1467:1488	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	2	17	theme	Dectin-1	230:237	arg1	A					248:248	A	248:248	A	248:248	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	2	17	theme	Dectin-1	230:237	arg1	isoforms					239:246	Dectin-1 isoforms A and B	230:254	Dectin-1 isoforms A and B	230:254	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	2	17	theme	Dectin-1	230:237	arg1	B					254:254	B	254:254	B	254:254	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	1	18	theme	major	118:122	arg1	receptor					124:131	a major receptor	116:131	a major receptor for fungal ß-glucans	116:152	Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity.
28303575	1	18	theme	major	118:122	arg1	Dectin-1					90:97	Dectin-1	90:97	Dectin-1	90:97	Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity.
28303575	4	19	theme	Dectin-1	489:496	arg1	isoform					498:504	either Dectin-1 isoform A or B	482:511	either Dectin-1 isoform A or B	482:511	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	9	20	theme	Differential	1114:1125	arg1	secretion					1153:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion was observed by cytometric bead array.
28303575	0	21	theme	immunity	80:87	arg1	quality					57:63	the signaling quality	43:63	the signaling quality of anti-fungal immunity	43:87	Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity.
28303575	5	22	theme	Intracellular	583:595	arg1	signaling					605:613	Intracellular protein signaling	583:613	Intracellular protein signaling	583:613	Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively.
28303575	11	23	theme	cytokine	1352:1359	arg1	secretion					1361:1369	unique cytokine secretion	1345:1369	unique cytokine secretion	1345:1369	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	9	24	theme	specific	1135:1142	arg1	secretion					1153:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion was observed by cytometric bead array.
28303575	8	25	theme	B	1105:1105	arg1	cells					1107:1111	isoform B cells	1097:1111	isoform B cells	1097:1111	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	3	26	from	expression	363:372	arg1	cells					417:421	human monocyte-derived cells	394:421	human monocyte-derived cells	394:421	Here, we analyzed the expression of both isoforms in human monocyte-derived cells.
28303575	7	27	gly	non-glycosylated	874:889	arg1	B					899:899	non-glycosylated isoform B	874:899	non-glycosylated isoform B	874:899	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	11	28	theme	expression	1383:1392	arg1	levels					1394:1399	varying expression levels	1375:1399	varying expression levels	1375:1399	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	11	29	theme	anti-fungal	1538:1548	arg1	immunity					1550:1557	anti-fungal immunity	1538:1557	anti-fungal immunity	1538:1557	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	3	30	theme	monocyte-derived	400:415	arg1	cells					417:421	human monocyte-derived cells	394:421	human monocyte-derived cells	394:421	Here, we analyzed the expression of both isoforms in human monocyte-derived cells.
28303575	0	31	theme	Isoform	0:6	arg1	localization					8:19	Isoform localization	0:19	Isoform localization of Dectin-1	0:31	Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity.
28303575	8	32	theme	glycosylation	945:957	arg1	Inhibition					931:940	Inhibition	931:940	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation	931:1080	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	4	33	theme	flow	528:531	arg1	cytometry					533:541	flow cytometry	528:541	flow cytometry	528:541	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	9	34	theme	cytometric	1179:1188	arg1	array					1195:1199	cytometric bead array	1179:1199	cytometric bead array	1179:1199	Differential isoform specific cytokine secretion was observed by cytometric bead array.
28303575	7	35	theme	isoform	815:821	arg1	A					823:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	10	36	theme	Dectin-1	1239:1246	arg1	n-glycosylation					1220:1234	n-glycosylation	1220:1234	n-glycosylation of Dectin-1	1220:1246	We show here that n-glycosylation of Dectin-1 is crucial for its cell surface expression and consequently signal transduction.
28303575	2	37	gly	glycosylation	321:333	arg2	site					335:338	its N-linked glycosylation site	308:338	its N-linked glycosylation site	308:338	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	6	38	theme	isoforms	783:790	arg1	expression					761:770	cell type-specific expression	742:770	cell type-specific expression of the two isoforms	742:790	Monocyte-derived cells showed cell type-specific expression of the two isoforms.
28303575	2	39	theme	site	335:338	arg1	presence					277:284	the presence	273:284	the presence of a stalk region and its N-linked glycosylation site	273:338	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	0	40	theme	signaling	47:55	arg1	quality					57:63	the signaling quality	43:63	the signaling quality of anti-fungal immunity	43:87	Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity.
28303575	7	41	theme	Glycosylated	793:804	arg1	A					823:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	8	42	theme	cell	995:998	arg1	expression					1008:1017	cell surface expression	995:1017	cell surface expression of isoform A. Signaling quality	995:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	2	43	theme	N-linked	312:319	arg1	site					335:338	its N-linked glycosylation site	308:338	its N-linked glycosylation site	308:338	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	8	44	theme	expression	1008:1017	arg1	abrogation					981:990	efficient abrogation	971:990	efficient abrogation of cell surface expression of isoform A. Signaling quality	971:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	2	45	theme	Human	195:199	arg1	populations					210:220	Human monocyte populations	195:220	Human monocyte populations	195:220	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	11	46	link	monocyte-derived	1431:1446	arg1	cells					1448:1452	monocyte-derived cells	1431:1452	monocyte-derived cells	1431:1452	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	8	47	theme	isoform	1022:1028	arg1	quality					1043:1049	isoform A. Signaling quality	1022:1049	isoform A. Signaling quality	1022:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	11	48	theme	isoform	1476:1482	arg1	mechanism					1514:1522	a cell type-specific mechanism	1493:1522	a cell type-specific mechanism of regulating anti-fungal immunity	1493:1557	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	11	48	theme	isoform	1476:1482	arg1	usage					1484:1488	distinct isoform usage	1467:1488	distinct isoform usage	1467:1488	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	8	49	theme	Signaling	1033:1041	arg1	quality					1043:1049	isoform A. Signaling quality	1022:1049	isoform A. Signaling quality	1022:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	4	50	theme	laser	556:560	arg1	microscopy					571:580	confocal laser scanning microscopy	547:580	confocal laser scanning microscopy	547:580	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	10	51	theme	surface	1272:1278	arg1	expression					1280:1289	its cell surface expression	1263:1289	its cell surface expression	1263:1289	We show here that n-glycosylation of Dectin-1 is crucial for its cell surface expression and consequently signal transduction.
28303575	5	52	theme	cytokine	619:626	arg1	production					628:637	cytokine production	619:637	cytokine production	619:637	Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively.
28303575	4	53	dep	isoform	498:504	arg1	B					511:511	B	511:511	B	511:511	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	4	53	dep	isoform	498:504	arg1	A					506:506	A	506:506	A	506:506	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	7	54	theme	isoform	891:897	arg1	B					899:899	non-glycosylated isoform B	874:899	non-glycosylated isoform B	874:899	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	7	55	located	localized	843:851	arg1	surface					865:871	the cell surface	856:871	the cell surface	856:871	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	7	55	located	localized	843:851	arg2	A					823:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	11	56	theme	Dectin-1	1410:1417	arg1	isoforms					1419:1426	human Dectin-1 isoforms	1404:1426	human Dectin-1 isoforms	1404:1426	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	2	57	theme	stalk	291:295	arg1	region					297:302	a stalk region	289:302	a stalk region	289:302	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	4	58	from	localization	437:448	arg1	lines					458:462	cell lines	453:462	cell lines stably expressing either Dectin-1 isoform A or B	453:511	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	7	59	theme	cell	860:863	arg1	surface					865:871	the cell surface	856:871	the cell surface	856:871	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	4	60	theme	cell	453:456	arg1	lines					458:462	cell lines	453:462	cell lines stably expressing either Dectin-1 isoform A or B	453:511	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	5	61	theme	bead	686:689	arg1	array					691:695	cytometric bead array	675:695	cytometric bead array	675:695	Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively.
28303575	10	62	theme	signal	1308:1313	arg1	transduction					1315:1326	signal transduction	1308:1326	signal transduction	1308:1326	We show here that n-glycosylation of Dectin-1 is crucial for its cell surface expression and consequently signal transduction.
28303575	0	63	theme	anti-fungal	68:78	arg1	immunity					80:87	anti-fungal immunity	68:87	anti-fungal immunity	68:87	Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity.
28303575	1	64	theme	fungal	137:142	arg1	ß-glucans					144:152	fungal ß-glucans	137:152	fungal ß-glucans	137:152	Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity.
28303575	6	65	link	Monocyte-derived	712:727	arg1	cells					729:733	Monocyte-derived cells	712:733	Monocyte-derived cells	712:733	Monocyte-derived cells showed cell type-specific expression of the two isoforms.
28303575	11	66	theme	varying	1375:1381	arg1	levels					1394:1399	varying expression levels	1375:1399	varying expression levels	1375:1399	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	9	67	theme	isoform	1127:1133	arg1	secretion					1153:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion was observed by cytometric bead array.
28303575	5	68	theme	protein	597:603	arg1	signaling					605:613	Intracellular protein signaling	583:613	Intracellular protein signaling	583:613	Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively.
28303575	9	69	theme	cytokine	1144:1151	arg1	secretion					1153:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion	1114:1161	Differential isoform specific cytokine secretion was observed by cytometric bead array.
28303575	11	70	theme	human	1404:1408	arg1	isoforms					1419:1426	human Dectin-1 isoforms	1404:1426	human Dectin-1 isoforms	1404:1426	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	6	71	theme	Monocyte-derived	712:727	arg1	cells					729:733	Monocyte-derived cells	712:733	Monocyte-derived cells	712:733	Monocyte-derived cells showed cell type-specific expression of the two isoforms.
28303575	0	72	theme	Dectin-1	24:31	arg1	localization					8:19	Isoform localization	0:19	Isoform localization of Dectin-1	0:31	Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity.
28303575	11	73	from	levels	1394:1399	arg1	cells					1448:1452	monocyte-derived cells	1431:1452	monocyte-derived cells	1431:1452	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	4	74	theme	confocal	547:554	arg1	microscopy					571:580	confocal laser scanning microscopy	547:580	confocal laser scanning microscopy	547:580	The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy.
28303575	9	75	theme	bead	1190:1193	arg1	array					1195:1199	cytometric bead array	1179:1199	cytometric bead array	1179:1199	Differential isoform specific cytokine secretion was observed by cytometric bead array.
28303575	3	76	theme	human	394:398	arg1	cells					417:421	human monocyte-derived cells	394:421	human monocyte-derived cells	394:421	Here, we analyzed the expression of both isoforms in human monocyte-derived cells.
28303575	11	77	from	secretion	1361:1369	arg1	cells					1448:1452	monocyte-derived cells	1431:1452	monocyte-derived cells	1431:1452	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	8	78	theme	efficient	971:979	arg1	abrogation					981:990	efficient abrogation	971:990	efficient abrogation of cell surface expression of isoform A. Signaling quality	971:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	3	79	theme	isoforms	382:389	arg1	expression					363:372	the expression	359:372	the expression of both isoforms in human monocyte-derived cells	359:421	Here, we analyzed the expression of both isoforms in human monocyte-derived cells.
28303575	11	80	theme	unique	1345:1350	arg1	secretion					1361:1369	unique cytokine secretion	1345:1369	unique cytokine secretion	1345:1369	Taken together, unique cytokine secretion and varying expression levels of human Dectin-1 isoforms on monocyte-derived cells may indicate distinct isoform usage as a cell type-specific mechanism of regulating anti-fungal immunity.
28303575	8	81	theme	isoform	1097:1103	arg1	cells					1107:1111	isoform B cells	1097:1111	isoform B cells	1097:1111	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	2	82	theme	glycosylation	321:333	arg1	site					335:338	its N-linked glycosylation site	308:338	its N-linked glycosylation site	308:338	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	7	83	theme	Dectin-1	806:813	arg1	A					823:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A	793:823	Glycosylated Dectin-1 isoform A was predominantly localized at the cell surface, non-glycosylated isoform B was retained intracellularly.
28303575	2	84	theme	monocyte	201:208	arg1	populations					210:220	Human monocyte populations	195:220	Human monocyte populations	195:220	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	8	85	theme	surface	1000:1006	arg1	expression					1008:1017	cell surface expression	995:1017	cell surface expression of isoform A. Signaling quality	995:1049	Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin-1 stimulation was reduced in isoform B cells.
28303575	2	86	link	N-linked	312:319	arg1	site					335:338	its N-linked glycosylation site	308:338	its N-linked glycosylation site	308:338	Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site.
28303575	6	87	theme	type-specific	747:759	arg1	expression					761:770	cell type-specific expression	742:770	cell type-specific expression of the two isoforms	742:790	Monocyte-derived cells showed cell type-specific expression of the two isoforms.
28410396	4	0	theme	NA	755:756	arg1	gene					758:761	the NA gene	751:761	the NA gene	751:761	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	8	1	theme	better	1900:1905	arg1	understanding					1907:1919	a better understanding	1898:1919	a better understanding of selection pressure exerted by antiviral use	1898:1966	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	2	2	theme	strains	303:309	arg1	emergence					270:278	the emergence	266:278	the emergence of new influenza virus strains with reduced susceptibility to NAIs	266:345	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	1	3	theme	influenza	222:230	arg1	A					232:232	influenza A	222:232	influenza A	222:232	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	4	4	contain	had	845:847	arg2	substitution					854:865	this substitution	849:865	this substitution	849:865	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	4	4	contain	had	845:847	arg1	4/485					838:842	4/485	838:842	4/485	838:842	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	4	4	contain	had	845:847	arg1	%					835:835	0.82%	831:835	0.82% (4/485)	831:843	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	3	5	theme	A	493:493	arg1	strains					547:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	4	6	theme	H275Y	733:737	arg1	mutation					739:746	the H275Y mutation	729:746	the H275Y mutation in the NA gene	729:761	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	7	7	theme	evolution	1540:1548	arg1	rates					1528:1532	The overall rates	1516:1532	The overall rates of NA evolution for influenza A viruses	1516:1572	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	7	7	theme	evolution	1540:1548	arg1	higher					1579:1584	higher	1579:1584	higher	1579:1584	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	8	8	theme	pressure	1934:1941	arg1	understanding					1907:1919	a better understanding	1898:1919	a better understanding of selection pressure exerted by antiviral use	1898:1966	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	3	9	theme	influenza	477:485	arg1	H1N1					495:498	H1N1	495:498	H1N1	495:498	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	3	9	theme	influenza	477:485	arg1	A					493:493	seasonal influenza virus A	468:493	seasonal influenza virus A(H1N1)	468:499	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	2	10	dep	appear	351:356	arg1	use					367:369	the use	363:369	the use of these antivirals	363:389	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	2	10	dep	appear	351:356	arg1	naturally					399:407	naturally	399:407	naturally	399:407	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	6	11	from	predictions	1397:1407	arg1	study					1264:1268	this study	1259:1268	this study	1259:1268	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	7	12	theme	overall	1520:1526	arg1	rates					1528:1532	The overall rates	1516:1532	The overall rates of NA evolution for influenza A viruses	1516:1572	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	7	12	theme	overall	1520:1526	arg1	higher					1579:1584	higher	1579:1584	higher	1579:1584	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	7	13	theme	A	1726:1726	arg1	viruses					1728:1734	influenza A viruses	1716:1734	influenza A viruses	1716:1734	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	5	14	theme	NA	909:910	arg1	gene					912:915	the NA gene	905:915	the NA gene	905:915	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	8	15	theme	changes	1781:1787	arg1	surveillance					1751:1762	The continual surveillance	1737:1762	The continual surveillance of the antigenic changes associated with the NA protein	1737:1818	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	6	16	theme	rates	1359:1363	arg1	estimations					1320:1330	the estimations	1316:1330	the estimations of nucleotide substitution rates and selection pressure	1316:1386	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	4	17	theme	485	767:769	arg1	A					771:771	485 A	767:771	485 A(H1N1)pdm09 strains circulating in Thailand	767:814	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	4	17	theme	485	767:769	arg1	H1N1					773:776	H1N1	773:776	H1N1	773:776	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	6	18	theme	glycosylation	1441:1453	arg1	sites					1455:1459	N-linked glycosylation sites	1432:1459	N-linked glycosylation sites	1432:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	6	19	theme	nucleotide	1335:1344	arg1	rates					1359:1363	nucleotide substitution rates	1335:1363	nucleotide substitution rates	1335:1363	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	7	20	theme	influenza	1554:1562	arg1	viruses					1566:1572	influenza A viruses	1554:1572	influenza A viruses	1554:1572	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	6	21	theme	B-cell	1412:1417	arg1	epitopes					1419:1426	B-cell epitopes	1412:1426	B-cell epitopes	1412:1426	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	5	22	from	mutations	1083:1091	arg1	site					1107:1110	the active site	1096:1110	the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs	1096:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	5	22	from	mutations	1083:1091	arg1	protein					1122:1128	the NA protein	1115:1128	the NA protein previously shown to be associated with reduced susceptibility to NAIs	1115:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	0	23	theme	A	58:58	arg1	viruses					66:72	seasonal influenza A and B viruses	39:72	seasonal influenza A and B viruses	39:72	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	6	24	theme	NA	1512:1513	arg1	evolution					1499:1507	the ongoing evolution	1487:1507	the ongoing evolution of NA	1487:1513	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	5	25	theme	NA	1011:1012	arg1	amplification					1019:1031	NA gene amplification	1011:1031	NA gene amplification	1011:1031	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	0	26	theme	B	64:64	arg1	viruses					66:72	seasonal influenza A and B viruses	39:72	seasonal influenza A and B viruses	39:72	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	5	27	theme	A	947:947	arg1	strains					999:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	6	28	theme	epitopes	1419:1426	arg1	predictions					1397:1407	the predictions	1393:1407	the predictions of B-cell epitopes and N-linked glycosylation sites	1393:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	6	28	theme	epitopes	1419:1426	arg1	analysis					1214:1221	Phylogenetic analysis	1201:1221	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world	1201:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	1	29	dep	treatment	197:205	arg1	the					193:195	the	193:195	the	193:195	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	0	30	from	Evolution	0:8	arg1	Thailand					77:84	Thailand	77:84	Thailand	77:84	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	8	31	theme	continual	1741:1749	arg1	surveillance					1751:1762	The continual surveillance	1737:1762	The continual surveillance of the antigenic changes associated with the NA protein	1737:1818	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	0	32	from	gene	31:34	arg1	Thailand					77:84	Thailand	77:84	Thailand	77:84	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	5	33	theme	active	1100:1105	arg1	site					1107:1110	the active site	1096:1110	the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs	1096:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	5	33	theme	active	1100:1105	arg1	protein					1122:1128	the NA protein	1115:1128	the NA protein previously shown to be associated with reduced susceptibility to NAIs	1115:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	1	34	theme	B	238:238	arg1	infection					246:254	B virus infection	238:254	B virus infection	238:254	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	6	35	theme	selection	1369:1377	arg1	pressure					1379:1386	selection pressure	1369:1386	selection pressure	1369:1386	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	2	36	theme	antivirals	380:389	arg1	use					367:369	the use	363:369	the use of these antivirals	363:389	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	5	37	theme	various	1064:1070	arg1	mutations					1083:1091	various amino acid mutations	1064:1091	various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs	1064:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	8	38	theme	antigenic	1771:1779	arg1	changes					1781:1787	the antigenic changes	1767:1787	the antigenic changes associated with the NA protein	1767:1818	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	1	39	theme	infection	246:254	arg1	control					211:217	control	211:217	control	211:217	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	39	theme	infection	246:254	arg1	treatment					197:205	treatment	197:205	treatment	197:205	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	7	40	theme	influenza	1647:1655	arg1	virus					1659:1663	influenza B virus	1647:1663	influenza B virus	1647:1663	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	5	41	theme	acid	1078:1081	arg1	mutations					1083:1091	various amino acid mutations	1064:1091	various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs	1064:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	0	42	theme	gene	31:34	arg1	Evolution					0:8	Evolution	0:8	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.	0:107	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	7	43	theme	influenza	1595:1603	arg1	virus					1607:1611	influenza B virus	1595:1611	influenza B virus	1595:1611	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	2	44	theme	virus	297:301	arg1	strains					303:309	new influenza virus strains	283:309	new influenza virus strains with reduced susceptibility to NAIs	283:345	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	3	45	theme	neuraminidase	436:448	arg1	sequences					455:463	the neuraminidase (NA) sequences	432:463	the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand	432:576	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	0	46	theme	seasonal	39:46	arg1	viruses					66:72	seasonal influenza A and B viruses	39:72	seasonal influenza A and B viruses	39:72	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	7	47	theme	nucleotide	1620:1629	arg1	level					1631:1635	the nucleotide level	1616:1635	the nucleotide level	1616:1635	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	8	48	theme	virus	1862:1866	arg1	database					1868:1875	the influenza virus database	1848:1875	the influenza virus database	1848:1875	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	3	49	theme	strains	547:553	arg1	sequences					455:463	the neuraminidase (NA) sequences	432:463	the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand	432:576	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	2	50	theme	new	283:285	arg1	strains					303:309	new influenza virus strains	283:309	new influenza virus strains with reduced susceptibility to NAIs	283:345	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	6	51	theme	strains	1246:1252	arg1	predictions					1397:1407	the predictions	1393:1407	the predictions of B-cell epitopes and N-linked glycosylation sites	1393:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	6	51	theme	strains	1246:1252	arg1	analysis					1214:1221	Phylogenetic analysis	1201:1221	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world	1201:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	5	52	theme	influenza	981:989	arg1	B					991:991	69 influenza B	978:991	69 influenza B	978:991	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	3	53	theme	B	539:539	arg1	strains					547:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	4	54	theme	oseltamivir	688:698	arg1	resistance					700:709	oseltamivir resistance	688:709	oseltamivir resistance (characterized by the H275Y mutation in the NA gene)	688:762	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	6	55	theme	influenza	1230:1238	arg1	strains					1246:1252	the influenza virus strains	1226:1252	the influenza virus strains from this study and elsewhere around the world	1226:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	5	56	theme	virus	993:997	arg1	strains					999:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	8	57	theme	NA	1809:1810	arg1	protein					1812:1818	the NA protein	1805:1818	the NA protein	1805:1818	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	7	58	theme	A	1564:1564	arg1	viruses					1566:1572	influenza A viruses	1554:1572	influenza A viruses	1554:1572	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	1	59	theme	virus	240:244	arg1	infection					246:254	B virus infection	238:254	B virus infection	238:254	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	5	60	theme	NA	1119:1120	arg1	protein					1122:1128	the NA protein	1115:1128	the NA protein previously shown to be associated with reduced susceptibility to NAIs	1115:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	3	61	theme	virus	487:491	arg1	H1N1					495:498	H1N1	495:498	H1N1	495:498	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	3	61	theme	virus	487:491	arg1	A					493:493	seasonal influenza virus A	468:493	seasonal influenza virus A(H1N1)	468:499	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	6	62	theme	Phylogenetic	1201:1212	arg1	analysis					1214:1221	Phylogenetic analysis	1201:1221	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world	1201:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	1	63	theme	A	232:232	arg1	control					211:217	control	211:217	control	211:217	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	63	theme	A	232:232	arg1	treatment					197:205	treatment	197:205	treatment	197:205	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	7	64	theme	NA	1537:1538	arg1	evolution					1540:1548	NA evolution	1537:1548	NA evolution	1537:1548	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	3	65	theme	substitutions	598:610	arg1	presence					586:593	the presence	582:593	the presence of substitutions previously reported to reduce susceptibility to NAIs	582:663	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	3	66	theme	seasonal	468:475	arg1	H1N1					495:498	H1N1	495:498	H1N1	495:498	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	3	66	theme	seasonal	468:475	arg1	A					493:493	seasonal influenza virus A	468:493	seasonal influenza virus A(H1N1)	468:499	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	8	67	theme	selection	1924:1932	arg1	pressure					1934:1941	selection pressure	1924:1941	selection pressure exerted by antiviral use	1924:1966	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	5	68	theme	reduced	1169:1175	arg1	susceptibility					1177:1190	reduced susceptibility	1169:1190	reduced susceptibility to NAIs	1169:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	8	69	dep	will	1820:1823	arg1	only					1829:1832	only	1829:1832	only	1829:1832	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	8	70	theme	antiviral	1954:1962	arg1	use					1964:1966	antiviral use	1954:1966	antiviral use	1954:1966	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	6	71	gly	glycosylation	1441:1453	arg2	sites					1455:1459	N-linked glycosylation sites	1432:1459	N-linked glycosylation sites	1432:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	4	72	theme	pdm09	778:782	arg1	strains					784:790	485 A(H1N1)pdm09 strains	767:790	485 A(H1N1)pdm09 strains circulating in Thailand	767:814	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	6	73	theme	sites	1455:1459	arg1	predictions					1397:1407	the predictions	1393:1407	the predictions of B-cell epitopes and N-linked glycosylation sites	1393:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	6	73	theme	sites	1455:1459	arg1	analysis					1214:1221	Phylogenetic analysis	1201:1221	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world	1201:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	1	74	used	used	184:187	arg2	NAIs					139:142	NAIs	139:142	NAIs	139:142	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	74	used	used	184:187	arg2	inhibitors					127:136	The neuraminidase inhibitors	109:136	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir	109:169	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	74	used	used	184:187	arg2	zanamivir					161:169	zanamivir	161:169	zanamivir	161:169	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	74	used	used	184:187	arg2	oseltamivir					145:155	oseltamivir	145:155	oseltamivir	145:155	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	5	75	theme	gene	912:915	arg1	evolution					892:900	the evolution	888:900	the evolution of the NA gene	888:915	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	3	76	theme	A	502:502	arg1	strains					547:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	6	77	theme	substitution	1346:1357	arg1	rates					1359:1363	nucleotide substitution rates	1335:1363	nucleotide substitution rates	1335:1363	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	7	78	theme	influenza	1716:1724	arg1	viruses					1728:1734	influenza A viruses	1716:1734	influenza A viruses	1716:1734	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	6	79	theme	N-linked	1432:1439	arg1	sites					1455:1459	N-linked glycosylation sites	1432:1459	N-linked glycosylation sites	1432:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	3	80	theme	A	516:516	arg1	strains					547:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	6	81	dep	together	1302:1309	arg1	with					1311:1314	with	1311:1314	with	1311:1314	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	4	82	theme	A	771:771	arg1	strains					784:790	485 A(H1N1)pdm09 strains	767:790	485 A(H1N1)pdm09 strains circulating in Thailand	767:814	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	0	83	from	Thailand	77:84	arg1	Evolution					0:8	Evolution	0:8	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.	0:107	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	1	84	theme	neuraminidase	113:125	arg1	inhibitors					127:136	The neuraminidase inhibitors	109:136	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir	109:169	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	84	theme	neuraminidase	113:125	arg1	zanamivir					161:169	zanamivir	161:169	zanamivir	161:169	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	84	theme	neuraminidase	113:125	arg1	oseltamivir					145:155	oseltamivir	145:155	oseltamivir	145:155	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	84	theme	neuraminidase	113:125	arg1	NAIs					139:142	NAIs	139:142	NAIs	139:142	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	0	85	theme	viruses	66:72	arg1	gene					31:34	the neuraminidase gene	13:34	the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015	13:106	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	6	86	link	N-linked	1432:1439	arg1	sites					1455:1459	N-linked glycosylation sites	1432:1459	N-linked glycosylation sites	1432:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	5	87	theme	gene	1014:1017	arg1	amplification					1019:1031	NA gene amplification	1011:1031	NA gene amplification	1011:1031	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	7	88	theme	genealogical	1680:1691	arg1	diversity					1693:1701	more genealogical diversity	1675:1701	more genealogical diversity	1675:1701	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	6	89	theme	ongoing	1491:1497	arg1	evolution					1499:1507	the ongoing evolution	1487:1507	the ongoing evolution of NA	1487:1513	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	4	90	from	mutation	739:746	arg1	gene					758:761	the NA gene	751:761	the NA gene	751:761	We initially examined oseltamivir resistance (characterized by the H275Y mutation in the NA gene) in 485 A(H1N1)pdm09 strains circulating in Thailand and found that 0.82% (4/485) had this substitution.
28410396	7	91	theme	B	1657:1657	arg1	virus					1659:1663	influenza B virus	1647:1663	influenza B virus	1647:1663	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	6	92	theme	pressure	1379:1386	arg1	estimations					1320:1330	the estimations	1316:1330	the estimations of nucleotide substitution rates and selection pressure	1316:1386	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	6	93	from	study	1264:1268	arg1	strains					1246:1252	the influenza virus strains	1226:1252	the influenza virus strains from this study and elsewhere around the world	1226:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	6	93	from	study	1264:1268	arg1	predictions					1397:1407	the predictions	1393:1407	the predictions of B-cell epitopes and N-linked glycosylation sites	1393:1459	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	6	93	from	study	1264:1268	arg1	analysis					1214:1221	Phylogenetic analysis	1201:1221	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world	1201:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	0	94	theme	neuraminidase	17:29	arg1	gene					31:34	the neuraminidase gene	13:34	the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015	13:106	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	5	95	theme	A	965:965	arg1	strains					999:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	1	96	dep	inhibitors	127:136	arg1	inhibitors					127:136	The neuraminidase inhibitors	109:136	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir	109:169	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	96	dep	inhibitors	127:136	arg1	zanamivir					161:169	zanamivir	161:169	zanamivir	161:169	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	1	96	dep	inhibitors	127:136	arg1	oseltamivir					145:155	oseltamivir	145:155	oseltamivir	145:155	The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection.
28410396	5	97	theme	amino	1072:1076	arg1	mutations					1083:1091	various amino acid mutations	1064:1091	various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs	1064:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	8	98	theme	influenza	1852:1860	arg1	database					1868:1875	the influenza virus database	1848:1875	the influenza virus database	1848:1875	The continual surveillance of the antigenic changes associated with the NA protein will not only contribute to the influenza virus database but may also provide a better understanding of selection pressure exerted by antiviral use.
28410396	5	99	theme	protein	1122:1128	arg1	site					1107:1110	the active site	1096:1110	the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs	1096:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	5	99	theme	protein	1122:1128	arg1	protein					1122:1128	the NA protein	1115:1128	the NA protein previously shown to be associated with reduced susceptibility to NAIs	1115:1198	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	0	100	theme	influenza	48:56	arg1	A					58:58	influenza A	48:58	influenza A	48:58	Evolution of the neuraminidase gene of seasonal influenza A and B viruses in Thailand between 2010 and 2015.
28410396	7	101	theme	B	1605:1605	arg1	virus					1607:1611	influenza B virus	1595:1611	influenza B virus	1595:1611	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	3	102	theme	virus	541:545	arg1	strains					547:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains	468:553	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	2	103	theme	influenza	287:295	arg1	strains					303:309	new influenza virus strains	283:309	new influenza virus strains with reduced susceptibility to NAIs	283:345	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	2	104	with	strains	303:309	arg1	susceptibility					324:337	reduced susceptibility	316:337	reduced susceptibility to NAIs	316:345	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28410396	6	105	from	analysis	1214:1221	arg1	study					1264:1268	this study	1259:1268	this study	1259:1268	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	3	106	theme	influenza	529:537	arg1	B					539:539	influenza B	529:539	influenza B	529:539	We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs.
28410396	6	107	theme	virus	1240:1244	arg1	strains					1246:1252	the influenza virus strains	1226:1252	the influenza virus strains from this study and elsewhere around the world	1226:1299	Phylogenetic analysis of the influenza virus strains from this study and elsewhere around the world, together with the estimations of nucleotide substitution rates and selection pressure, and the predictions of B-cell epitopes and N-linked glycosylation sites all provided evidence for the ongoing evolution of NA.
28410396	5	108	theme	B	991:991	arg1	strains					999:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains	944:1005	To further evaluate the evolution of the NA gene, we also randomly selected 98 A(H1N1)pdm09, 158 A(H3N2), and 69 influenza B virus strains for NA gene amplification and sequencing, which revealed various amino acid mutations in the active site of the NA protein previously shown to be associated with reduced susceptibility to NAIs.
28410396	7	109	contain	possessed	1665:1673	arg2	diversity					1693:1701	more genealogical diversity	1675:1701	more genealogical diversity	1675:1701	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	7	109	contain	possessed	1665:1673	arg1	virus					1659:1663	influenza B virus	1647:1663	influenza B virus	1647:1663	The overall rates of NA evolution for influenza A viruses were higher than for influenza B virus at the nucleotide level, although influenza B virus possessed more genealogical diversity than that of influenza A viruses.
28410396	2	110	theme	reduced	316:322	arg1	susceptibility					324:337	reduced susceptibility	316:337	reduced susceptibility to NAIs	316:345	However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally.
28844738	0	0	theme	Immunoglobulin	76:89	arg1	IgE					94:96	IgE	94:96	IgE	94:96	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	0	theme	Immunoglobulin	76:89	arg1	E					91:91	immunoglobulin E. Immunoglobulin E	58:91	immunoglobulin E. Immunoglobulin E (IgE)	58:97	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	7	1	theme	simplified	1154:1163	arg1	method					1165:1170	A simplified method	1152:1170	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures	1152:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	3	2	link	N-linked	521:528	arg1	site					544:547	the N-linked glycosylation site	517:547	the N-linked glycosylation site conserved in other isotypes	517:575	This domain also contains the N-linked glycosylation site conserved in other isotypes.
28844738	1	3	dep	Cε3	321:323	arg1	the					312:314	the	312:314	the	312:314	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	3	dep	Cε3	321:323	arg1	domains					333:339	domains	333:339	domains	333:339	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	0	4	theme	E.	73:74	arg1	IgE					94:96	IgE	94:96	IgE	94:96	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	4	theme	E.	73:74	arg1	E					91:91	immunoglobulin E. Immunoglobulin E	58:91	immunoglobulin E. Immunoglobulin E (IgE)	58:97	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	5	from	sensitivity	8:18	arg1	IgE					94:96	IgE	94:96	IgE	94:96	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	5	from	sensitivity	8:18	arg1	E					91:91	immunoglobulin E. Immunoglobulin E	58:91	immunoglobulin E. Immunoglobulin E (IgE)	58:97	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	5	6	theme	greatest	958:965	arg1	flexibility					977:987	intrinsic flexibility	967:987	intrinsic flexibility	967:987	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	1	7	theme	Cε4	329:331	arg1	region					293:298	the Fc region	286:298	the Fc region	286:298	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	7	theme	Cε4	329:331	arg1	dimer					303:307	a dimer	301:307	a dimer of the Cε2, Cε3 and Cε4 domains	301:339	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	8	8	theme	fluorimetric	1383:1394	arg1	analysis					1396:1403	differential scanning fluorimetric analysis	1361:1403	differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4	1361:1424	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	3	9	gly	glycosylation	530:542	arg2	site					544:547	the N-linked glycosylation site	517:547	the N-linked glycosylation site conserved in other isotypes	517:575	This domain also contains the N-linked glycosylation site conserved in other isotypes.
28844738	1	10	from	CD23	253:256	arg1	cells					243:247	mast cells	238:247	mast cells	238:247	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	10	from	CD23	253:256	arg1	cells					263:267	B cells	261:267	B cells	261:267	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	4	11	from	resolutions	652:662	arg1	structures					605:614	the crystal structures	593:614	the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains	593:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	4	12	theme	highest	644:650	arg1	resolutions					652:662	the highest resolutions	640:662	the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains	640:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	8	13	theme	IgE-Fc	1408:1413	arg1	analysis					1396:1403	differential scanning fluorimetric analysis	1361:1403	differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4	1361:1424	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	7	14	theme	CD23	1329:1332	arg1	states					1340:1345	the FcεRI and CD23 bound states	1315:1345	the FcεRI and CD23 bound states	1315:1345	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	5	15	theme	quaternary	993:1002	arg1	variation					1015:1023	quaternary structural variation	993:1023	quaternary structural variation within IgE-Fc	993:1037	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	7	16	from	structures	1265:1274	arg1	structures					1201:1210	the quaternary structures	1186:1210	the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures	1186:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	7	17	theme	quaternary	1190:1199	arg1	structures					1201:1210	the quaternary structures	1186:1210	the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures	1186:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	1	18	theme	Fc	290:291	arg1	region					293:298	the Fc region	286:298	the Fc region	286:298	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	18	theme	Fc	290:291	arg1	dimer					303:307	a dimer	301:307	a dimer of the Cε2, Cε3 and Cε4 domains	301:339	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	0	19	theme	diseases	171:178	arg1	mechanisms					148:157	the mechanisms	144:157	the mechanisms of allergic diseases such as asthma	144:193	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	7	20	theme	receptor-bound	1243:1256	arg1	structures					1265:1274	free and receptor-bound IgE-Fc structures	1234:1274	free and receptor-bound IgE-Fc structures	1234:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	0	21	theme	allergic	162:169	arg1	diseases					171:178	allergic diseases	162:178	allergic diseases such as asthma	162:193	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	21	theme	allergic	162:169	arg1	asthma					188:193	asthma	188:193	asthma	188:193	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	6	22	theme	well-ordered	1059:1070	arg1	carbohydrate					1072:1083	well-ordered carbohydrate	1059:1083	well-ordered carbohydrate	1059:1083	Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be seen within the same Cε3 domain.
28844738	5	23	theme	earlier	881:887	arg1	IgE-Fc					889:894	all earlier IgE-Fc and Fcε3-4 structures	877:916	IgE-Fc	889:894	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	7	24	theme	IgE-Fc	1258:1263	arg1	structures					1265:1274	free and receptor-bound IgE-Fc structures	1234:1274	free and receptor-bound IgE-Fc structures	1234:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	8	25	theme	susceptible	1460:1470	arg1	Cε3					1437:1439	Cε3	1437:1439	Cε3	1437:1439	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	8	25	theme	susceptible	1460:1470	arg1	domain					1448:1453	the domain	1444:1453	the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE	1444:1576	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	5	26	theme	B-factors	843:851	arg1	Analysis					810:817	Analysis	810:817	Analysis of the crystallographic B-factors of these	810:860	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	5	27	theme	structural	1004:1013	arg1	variation					1015:1023	quaternary structural variation	993:1023	quaternary structural variation within IgE-Fc	993:1037	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	7	28	theme	free	1234:1237	arg1	structures					1265:1274	free and receptor-bound IgE-Fc structures	1234:1274	free and receptor-bound IgE-Fc structures	1234:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	0	29	theme	Thermal	0:6	arg1	antibody					106:113	the antibody	102:113	the antibody that plays a central role in the mechanisms of allergic diseases such as asthma	102:193	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	29	theme	Thermal	0:6	arg1	flexibility					24:34	flexibility	24:34	flexibility	24:34	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	29	theme	Thermal	0:6	arg1	sensitivity					8:18	Thermal sensitivity	0:18	Thermal sensitivity	0:18	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	7	30	from	structures	1201:1210	arg1	structures					1265:1274	free and receptor-bound IgE-Fc structures	1234:1274	free and receptor-bound IgE-Fc structures	1234:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	4	31	theme	IgE-Fc	619:624	arg1	structures					605:614	the crystal structures	593:614	the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains	593:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	8	32	theme	differential	1361:1372	arg1	analysis					1396:1403	differential scanning fluorimetric analysis	1361:1403	differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4	1361:1424	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	8	33	theme	Fcε3-4	1419:1424	arg1	analysis					1396:1403	differential scanning fluorimetric analysis	1361:1403	differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4	1361:1424	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	1	34	theme	mast	238:241	arg1	cells					243:247	mast cells	238:247	mast cells	238:247	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	2	35	theme	receptor	429:436	arg1	binding					438:444	receptor binding	429:444	receptor binding	429:444	A sub-fragment lacking the Cε2 domains, Fcε3-4, also binds to both receptors, although receptor binding almost exclusively involves the Cε3 domains.
28844738	6	36	theme	Cε3	1140:1142	arg1	domain					1144:1149	the same Cε3 domain	1131:1149	the same Cε3 domain	1131:1149	Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be seen within the same Cε3 domain.
28844738	5	37	theme	Cε3	934:936	arg1	domains					938:944	the Cε3 domains	930:944	the Cε3 domains	930:944	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	7	38	theme	domains	1223:1229	arg1	structures					1201:1210	the quaternary structures	1186:1210	the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures	1186:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	7	39	theme	bound	1334:1338	arg1	states					1340:1345	the FcεRI and CD23 bound states	1315:1345	the FcεRI and CD23 bound states	1315:1345	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	1	40	from	FcεRI	229:233	arg1	cells					243:247	mast cells	238:247	mast cells	238:247	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	40	from	FcεRI	229:233	arg1	cells					263:267	B cells	261:267	B cells	261:267	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	3	41	theme	glycosylation	530:542	arg1	site					544:547	the N-linked glycosylation site	517:547	the N-linked glycosylation site conserved in other isotypes	517:575	This domain also contains the N-linked glycosylation site conserved in other isotypes.
28844738	4	42	theme	Fcε3-4	630:635	arg1	structures					605:614	the crystal structures	593:614	the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains	593:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	2	43	theme	Cε2	369:371	arg1	domains					373:379	the Cε2 domains	365:379	the Cε2 domains	365:379	A sub-fragment lacking the Cε2 domains, Fcε3-4, also binds to both receptors, although receptor binding almost exclusively involves the Cε3 domains.
28844738	5	44	theme	intrinsic	967:975	arg1	flexibility					977:987	intrinsic flexibility	967:987	intrinsic flexibility	967:987	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	8	45	theme	thermally-induced	1475:1491	arg1	unfolding					1493:1501	thermally-induced unfolding	1475:1501	thermally-induced unfolding	1475:1501	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	7	46	theme	FcεRI	1319:1323	arg1	states					1340:1345	the FcεRI and CD23 bound states	1315:1345	the FcεRI and CD23 bound states	1315:1345	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	8	47	theme	scanning	1374:1381	arg1	analysis					1396:1403	differential scanning fluorimetric analysis	1361:1403	differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4	1361:1424	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	7	48	theme	Cε3	1219:1221	arg1	domains					1223:1229	the Cε3 domains	1215:1229	the Cε3 domains in free and receptor-bound IgE-Fc structures	1215:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	0	49	theme	domains	47:53	arg1	antibody					106:113	the antibody	102:113	the antibody that plays a central role in the mechanisms of allergic diseases such as asthma	102:193	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	49	theme	domains	47:53	arg1	flexibility					24:34	flexibility	24:34	flexibility	24:34	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	49	theme	domains	47:53	arg1	sensitivity					8:18	Thermal sensitivity	0:18	Thermal sensitivity	0:18	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	8	50	theme	responsible	1508:1518	arg1	Cε3					1437:1439	Cε3	1437:1439	Cε3	1437:1439	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	8	50	theme	responsible	1508:1518	arg1	domain					1448:1453	the domain	1444:1453	the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE	1444:1576	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	4	51	theme	protein	793:799	arg1	domains					801:807	protein domains	793:807	protein domains	793:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	3	52	theme	N-linked	521:528	arg1	site					544:547	the N-linked glycosylation site	517:547	the N-linked glycosylation site conserved in other isotypes	517:575	This domain also contains the N-linked glycosylation site conserved in other isotypes.
28844738	4	53	theme	crystal	597:603	arg1	structures					605:614	the crystal structures	593:614	the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains	593:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	0	54	theme	Cε3	43:45	arg1	domains					47:53	the Cε3 domains	39:53	the Cε3 domains	39:53	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	1	55	theme	B	261:261	arg1	cells					263:267	B cells	261:267	B cells	261:267	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	3	56	theme	other	562:566	arg1	isotypes					568:575	other isotypes	562:575	other isotypes	562:575	This domain also contains the N-linked glycosylation site conserved in other isotypes.
28844738	4	57	theme	unprecedented	719:731	arg1	detail					733:738	unprecedented detail	719:738	unprecedented detail regarding the carbohydrate and its interactions with protein domains	719:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	7	58	from	domains	1223:1229	arg1	structures					1265:1274	free and receptor-bound IgE-Fc structures	1234:1274	free and receptor-bound IgE-Fc structures	1234:1274	A simplified method for comparing the quaternary structures of the Cε3 domains in free and receptor-bound IgE-Fc structures is presented, which clearly delineates the FcεRI and CD23 bound states.
28844738	4	59	with	interactions	775:786	arg1	domains					801:807	protein domains	793:807	protein domains	793:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	8	60	theme	IgE	1574:1576	arg1	temperature					1559:1569	the characteristically low melting temperature	1524:1569	the characteristically low melting temperature of IgE	1524:1576	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	6	61	theme	same	1135:1138	arg1	domain					1144:1149	the same Cε3 domain	1131:1149	the same Cε3 domain	1131:1149	Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be seen within the same Cε3 domain.
28844738	5	62	dep	together	863:870	arg1	with					872:875	with	872:875	with	872:875	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	5	63	theme	these	856:860	arg1	B-factors					843:851	the crystallographic B-factors	822:851	the crystallographic B-factors of these	822:860	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	5	64	dep	flexibility	977:987	arg1	the					954:956	the	954:956	the	954:956	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	0	65	theme	central	128:134	arg1	role					136:139	a central role	126:139	a central role	126:139	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	1	66	theme	Cε3	321:323	arg1	region					293:298	the Fc region	286:298	the Fc region	286:298	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	66	theme	Cε3	321:323	arg1	dimer					303:307	a dimer	301:307	a dimer of the Cε2, Cε3 and Cε4 domains	301:339	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	67	with	Interactions	196:207	arg1	receptors					218:226	its receptors	214:226	its receptors	214:226	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	67	with	Interactions	196:207	arg1	CD23					253:256	CD23	253:256	CD23 on B cells	253:267	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	1	67	with	Interactions	196:207	arg1	FcεRI					229:233	FcεRI	229:233	FcεRI on mast cells	229:247	Interactions with its receptors, FcεRI on mast cells and CD23 on B cells, are mediated by the Fc region, a dimer of the Cε2, Cε3 and Cε4 domains.
28844738	5	68	theme	crystallographic	826:841	arg1	B-factors					843:851	the crystallographic B-factors	822:851	the crystallographic B-factors of these	822:860	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	8	69	theme	low	1547:1549	arg1	temperature					1559:1569	the characteristically low melting temperature	1524:1569	the characteristically low melting temperature of IgE	1524:1576	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
28844738	0	70	theme	immunoglobulin	58:71	arg1	IgE					94:96	IgE	94:96	IgE	94:96	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	70	theme	immunoglobulin	58:71	arg1	E					91:91	immunoglobulin E. Immunoglobulin E	58:91	immunoglobulin E. Immunoglobulin E (IgE)	58:97	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	5	71	theme	Fcε3-4	900:905	arg1	structures					907:916	all earlier IgE-Fc and Fcε3-4 structures	877:916	structures	907:916	Analysis of the crystallographic B-factors of these, together with all earlier IgE-Fc and Fcε3-4 structures, shows that the Cε3 domains exhibit the greatest intrinsic flexibility and quaternary structural variation within IgE-Fc.
28844738	6	72	theme	disordered	1089:1098	arg1	polypeptide					1100:1110	disordered polypeptide	1089:1110	disordered polypeptide	1089:1110	Intriguingly, both well-ordered carbohydrate and disordered polypeptide can be seen within the same Cε3 domain.
28844738	4	73	with	carbohydrate	754:765	arg1	domains					801:807	protein domains	793:807	protein domains	793:807	We report here the crystal structures of IgE-Fc and Fcε3-4 at the highest resolutions yet determined, 1.75Å and 2.0Å respectively, revealing unprecedented detail regarding the carbohydrate and its interactions with protein domains.
28844738	3	74	contain	contains	508:515	arg1	domain					496:501	This domain	491:501	This domain	491:501	This domain also contains the N-linked glycosylation site conserved in other isotypes.
28844738	3	74	contain	contains	508:515	arg2	site					544:547	the N-linked glycosylation site	517:547	the N-linked glycosylation site conserved in other isotypes	517:575	This domain also contains the N-linked glycosylation site conserved in other isotypes.
28844738	0	75	from	flexibility	24:34	arg1	IgE					94:96	IgE	94:96	IgE	94:96	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	0	75	from	flexibility	24:34	arg1	E					91:91	immunoglobulin E. Immunoglobulin E	58:91	immunoglobulin E. Immunoglobulin E (IgE)	58:97	Thermal sensitivity and flexibility of the Cε3 domains in immunoglobulin E. Immunoglobulin E (IgE) is the antibody that plays a central role in the mechanisms of allergic diseases such as asthma.
28844738	8	76	theme	melting	1551:1557	arg1	temperature					1559:1569	the characteristically low melting temperature	1524:1569	the characteristically low melting temperature of IgE	1524:1576	Importantly, differential scanning fluorimetric analysis of IgE-Fc and Fcε3-4 identifies Cε3 as the domain most susceptible to thermally-induced unfolding, and responsible for the characteristically low melting temperature of IgE.
29258330	0	0	theme	Coreceptor	93:102	arg1	Profile					110:116	Different Coreceptor Usage Profile	83:116	Different Coreceptor Usage Profile	83:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	2	1	theme	N-linked	485:492	arg1	sites					508:512	N-linked glycosylation sites	485:512	N-linked glycosylation sites	485:512	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	1	2	from	signatures	172:181	arg1	glycoprotein					203:214	envelope surface glycoprotein	186:214	envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains	186:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	2	3	theme	sequences	353:361	arg1	inspection					325:334	inspection	325:334	inspection of aligned HIV-2 sequences	325:361	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	0	4	theme	Different	83:91	arg1	Profile					110:116	Different Coreceptor Usage Profile	83:116	Different Coreceptor Usage Profile	83:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	3	5	theme	particular	661:670	arg1	pattern					689:695	any particular coreceptor usage pattern	657:695	any particular coreceptor usage pattern	657:695	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	5	6	theme	preferential	987:998	arg1	usage					1000:1004	the preferential usage	983:1004	the preferential usage of a specific coreceptor	983:1029	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	2	7	theme	HIV-2	347:351	arg1	sequences					353:361	aligned HIV-2 sequences	339:361	aligned HIV-2 sequences	339:361	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	0	8	from	Characterization	0:15	arg1	Isolates					69:76	HIV-2 Primary Isolates	55:76	HIV-2 Primary Isolates with Different Coreceptor Usage Profile	55:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	5	9	theme	V3	944:945	arg1	regions					947:953	V3 regions	944:953	V3 regions	944:953	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	1	10	theme	different	264:272	arg1	strains					311:317	different human immunodeficiency virus (HIV)-2 strains	264:317	different human immunodeficiency virus (HIV)-2 strains	264:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	0	11	theme	Usage	104:108	arg1	Profile					110:116	Different Coreceptor Usage Profile	83:116	Different Coreceptor Usage Profile	83:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	1	12	theme	human	274:278	arg1	HIV					304:306	HIV	304:306	HIV	304:306	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	1	12	theme	human	274:278	arg1	virus					297:301	human immunodeficiency virus	274:301	different human immunodeficiency virus (HIV)-2 strains	264:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	3	13	from	positions	629:637	arg1	region					645:650	V3 region	642:650	V3 region with any particular coreceptor usage pattern	642:695	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	2	14	theme	aligned	339:345	arg1	sequences					353:361	aligned HIV-2 sequences	339:361	aligned HIV-2 sequences	339:361	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	1	15	gly	glycoprotein	203:214	arg1	glycoprotein					203:214	envelope surface glycoprotein	186:214	envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains	186:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	0	16	with	Isolates	69:76	arg1	Profile					110:116	Different Coreceptor Usage Profile	83:116	Different Coreceptor Usage Profile	83:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	4	17	theme	genetic	743:749	arg1	distinct					789:796	distinct	789:796	distinct	789:796	In conclusion, we showed that for HIV-2, the genetic determinants for coreceptor usage are distinct from those of HIV-1.
29258330	4	17	theme	genetic	743:749	arg1	determinants					751:762	the genetic determinants	739:762	the genetic determinants for coreceptor usage	739:783	In conclusion, we showed that for HIV-2, the genetic determinants for coreceptor usage are distinct from those of HIV-1.
29258330	3	18	from	charge	598:603	arg1	region					645:650	V3 region	642:650	V3 region with any particular coreceptor usage pattern	642:695	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	1	19	theme	molecular	162:170	arg1	signatures					172:181	molecular signatures	162:181	molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains	162:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	2	20	theme	heterogeneity	443:455	arg1	degree					413:418	the highest degree	401:418	the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length	401:534	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	2	21	from	polymorphisms	468:480	arg1	sequence					515:522	sequence	515:522	sequence	515:522	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	2	21	from	polymorphisms	468:480	arg1	length					529:534	length	529:534	length	529:534	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	2	21	from	polymorphisms	468:480	arg1	sites					508:512	N-linked glycosylation sites	485:512	N-linked glycosylation sites	485:512	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	5	22	theme	discrete	892:899	arg1	positions					912:920	discrete amino acid positions	892:920	discrete amino acid positions either in V1/V2 or in V3 regions	892:953	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	2	23	theme	V1/V2	381:385	arg1	region					387:392	V1/V2 region	381:392	V1/V2 region	381:392	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	2	24	theme	sequence	434:441	arg1	heterogeneity					443:455	amino acid sequence heterogeneity	423:455	amino acid sequence heterogeneity	423:455	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	2	25	gly	glycosylation	494:506	arg2	sites					508:512	N-linked glycosylation sites	485:512	N-linked glycosylation sites	485:512	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	3	26	theme	coreceptor	672:681	arg1	pattern					689:695	any particular coreceptor usage pattern	657:695	any particular coreceptor usage pattern	657:695	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	2	27	theme	acid	429:432	arg1	heterogeneity					443:455	amino acid sequence heterogeneity	423:455	amino acid sequence heterogeneity	423:455	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	1	28	theme	immunodeficiency	280:295	arg1	HIV					304:306	HIV	304:306	HIV	304:306	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	1	28	theme	immunodeficiency	280:295	arg1	virus					297:301	human immunodeficiency virus	274:301	different human immunodeficiency virus (HIV)-2 strains	264:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	5	29	theme	amino	901:905	arg1	positions					912:920	discrete amino acid positions	892:920	discrete amino acid positions either in V1/V2 or in V3 regions	892:953	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	1	30	theme	envelope	186:193	arg1	glycoprotein					203:214	envelope surface glycoprotein	186:214	envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains	186:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	0	31	theme	Surface	29:35	arg1	Glycoprotein					37:48	Envelope Surface Glycoprotein	20:48	Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile	20:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	1	32	theme	virus	297:301	arg1	strains					311:317	different human immunodeficiency virus (HIV)-2 strains	264:317	different human immunodeficiency virus (HIV)-2 strains	264:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	5	33	theme	coreceptor	1020:1029	arg1	usage					1000:1004	the preferential usage	983:1004	the preferential usage of a specific coreceptor	983:1029	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	5	34	theme	acid	907:910	arg1	positions					912:920	discrete amino acid positions	892:920	discrete amino acid positions either in V1/V2 or in V3 regions	892:953	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	1	35	theme	surface	195:201	arg1	glycoprotein					203:214	envelope surface glycoprotein	186:214	envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains	186:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	0	36	theme	Envelope	20:27	arg1	Glycoprotein					37:48	Envelope Surface Glycoprotein	20:48	Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile	20:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	5	37	theme	molecular	862:870	arg1	signature					872:880	any molecular signature	858:880	any molecular signature	858:880	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	2	38	theme	highest	405:411	arg1	degree					413:418	the highest degree	401:418	the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length	401:534	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	3	39	with	region	645:650	arg1	pattern					689:695	any particular coreceptor usage pattern	657:695	any particular coreceptor usage pattern	657:695	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	0	40	theme	Glycoprotein	37:48	arg1	Characterization					0:15	Characterization	0:15	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.	0:117	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	3	41	theme	amino	618:622	arg1	positions					629:637	specific amino acid positions	609:637	specific amino acid positions	609:637	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	2	42	theme	amino	423:427	arg1	heterogeneity					443:455	amino acid sequence heterogeneity	423:455	amino acid sequence heterogeneity	423:455	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	2	43	link	N-linked	485:492	arg1	sites					508:512	N-linked glycosylation sites	485:512	N-linked glycosylation sites	485:512	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	0	44	theme	Primary	61:67	arg1	Isolates					69:76	HIV-2 Primary Isolates	55:76	HIV-2 Primary Isolates with Different Coreceptor Usage Profile	55:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	0	45	from	Isolates	69:76	arg1	Characterization					0:15	Characterization	0:15	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.	0:117	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	0	45	from	Isolates	69:76	arg1	Glycoprotein					37:48	Envelope Surface Glycoprotein	20:48	Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile	20:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	1	46	theme	main	123:126	arg1	goal					128:131	The main goal	119:131	The main goal of this work	119:144	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	0	47	theme	HIV-2	55:59	arg1	Isolates					69:76	HIV-2 Primary Isolates	55:76	HIV-2 Primary Isolates with Different Coreceptor Usage Profile	55:116	Characterization of Envelope Surface Glycoprotein from HIV-2 Primary Isolates with Different Coreceptor Usage Profile.
29258330	3	48	theme	acid	624:627	arg1	positions					629:637	specific amino acid positions	609:637	specific amino acid positions	609:637	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	5	49	theme	specific	1011:1018	arg1	coreceptor					1020:1029	a specific coreceptor	1009:1029	a specific coreceptor	1009:1029	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	5	50	from	positions	912:920	arg1	regions					947:953	V3 regions	944:953	V3 regions	944:953	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	5	50	from	positions	912:920	arg1	V1/V2					932:936	V1/V2	932:936	V1/V2	932:936	More specifically, we did not identify any molecular signature, based on discrete amino acid positions either in V1/V2 or in V3 regions, which could be assigned to the preferential usage of a specific coreceptor.
29258330	3	51	theme	V3	642:643	arg1	region					645:650	V3 region	642:650	V3 region with any particular coreceptor usage pattern	642:695	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	3	52	theme	specific	609:616	arg1	positions					629:637	specific amino acid positions	609:637	specific amino acid positions	609:637	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	3	53	theme	net	594:596	arg1	charge					598:603	the net charge	590:603	the net charge	590:603	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	1	54	theme	work	141:144	arg1	goal					128:131	The main goal	119:131	The main goal of this work	119:144	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29258330	2	55	theme	glycosylation	494:506	arg1	sites					508:512	N-linked glycosylation sites	485:512	N-linked glycosylation sites	485:512	From inspection of aligned HIV-2 sequences, we verified that V1/V2 region showed the highest degree of amino acid sequence heterogeneity, including polymorphisms in N-linked glycosylation sites, sequence, and length.
29258330	3	56	theme	usage	683:687	arg1	pattern					689:695	any particular coreceptor usage pattern	657:695	any particular coreceptor usage pattern	657:695	Furthermore, we did not find any correlation between the net charge and specific amino acid positions in V3 region with any particular coreceptor usage pattern.
29258330	4	57	theme	coreceptor	768:777	arg1	usage					779:783	coreceptor usage	768:783	coreceptor usage	768:783	In conclusion, we showed that for HIV-2, the genetic determinants for coreceptor usage are distinct from those of HIV-1.
29258330	4	58	from	those	803:807	arg1	distinct					789:796	distinct	789:796	distinct	789:796	In conclusion, we showed that for HIV-2, the genetic determinants for coreceptor usage are distinct from those of HIV-1.
29258330	4	58	from	those	803:807	arg1	determinants					751:762	the genetic determinants	739:762	the genetic determinants for coreceptor usage	739:783	In conclusion, we showed that for HIV-2, the genetic determinants for coreceptor usage are distinct from those of HIV-1.
29258330	1	59	theme	coreceptor	244:253	arg1	usage					255:259	coreceptor usage	244:259	coreceptor usage by different human immunodeficiency virus (HIV)-2 strains	244:317	The main goal of this work was to identify molecular signatures in envelope surface glycoprotein that may be correlated with coreceptor usage by different human immunodeficiency virus (HIV)-2 strains.
29784879	0	0	theme	ER	73:74	arg1	protein					117:123	ER degradation-enhancing α-mannosidase-like protein 3	73:125	ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3)	73:133	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	0	0	theme	ER	73:74	arg1	EDEM3					128:132	EDEM3	128:132	EDEM3	128:132	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	5	1	theme	molecular	643:651	arg1	mechanism					653:661	the molecular mechanism	639:661	the molecular mechanism of mannose removal by EDEMs	639:689	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	6	2	theme	disulfide	1049:1057	arg1	bond					1059:1062	a disulfide bond	1047:1062	a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain	1047:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	3	3	theme	glycoproteins	482:494	arg1	disposal					460:467	disposal	460:467	disposal of misfolded glycoproteins	460:494	In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins.
29784879	4	4	theme	ER	568:569	arg1	EDEMs					622:626	EDEMs	622:626	EDEMs	622:626	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	4	4	theme	ER	568:569	arg1	proteins					612:619	ER degradation-enhancing α-mannosidase-like proteins	568:619	ER degradation-enhancing α-mannosidase-like proteins (EDEMs)	568:627	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	6	5	theme	bond	1059:1062	arg1	formation					1034:1042	formation	1034:1042	formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain	1034:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	5	6	gly	glycoprotein	865:876	arg1	glycoprotein					865:876	a misfolded glycoprotein	853:876	a misfolded glycoprotein	853:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	0	7	theme	α-mannosidase-like	98:115	arg1	protein					117:123	ER degradation-enhancing α-mannosidase-like protein 3	73:125	ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3)	73:133	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	0	7	theme	α-mannosidase-like	98:115	arg1	EDEM3					128:132	EDEM3	128:132	EDEM3	128:132	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	7	8	theme	glycoprotein	1335:1346	arg1	locus					1366:1370	the glycoprotein T-cell receptor α locus	1331:1370	the glycoprotein T-cell receptor α locus (TCRα)	1331:1377	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	8	theme	glycoprotein	1335:1346	arg1	substrate					1320:1328	the model misfolded substrate	1300:1328	the model misfolded substrate	1300:1328	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	8	theme	glycoprotein	1335:1346	arg1	TCRα					1373:1376	TCRα	1373:1376	TCRα	1373:1376	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	9	dep	in	1175:1176	arg1	vitro					1178:1182	vitro	1178:1182	vitro	1178:1182	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	10	theme	misfolded	1310:1318	arg1	locus					1366:1370	the glycoprotein T-cell receptor α locus	1331:1370	the glycoprotein T-cell receptor α locus (TCRα)	1331:1377	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	10	theme	misfolded	1310:1318	arg1	substrate					1320:1328	the model misfolded substrate	1300:1328	the model misfolded substrate	1300:1328	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	4	11	theme	α-mannosidase-like	593:610	arg1	EDEMs					622:626	EDEMs	622:626	EDEMs	622:626	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	4	11	theme	α-mannosidase-like	593:610	arg1	proteins					612:619	ER degradation-enhancing α-mannosidase-like proteins	568:619	ER degradation-enhancing α-mannosidase-like proteins (EDEMs)	568:627	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	0	12	theme	degradation-enhancing	76:96	arg1	protein					117:123	ER degradation-enhancing α-mannosidase-like protein 3	73:125	ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3)	73:133	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	0	12	theme	degradation-enhancing	76:96	arg1	EDEM3					128:132	EDEM3	128:132	EDEM3	128:132	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	8	13	dep	findings	1487:1494	arg1	the					1468:1470	the	1468:1470	the	1468:1470	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	8	13	dep	findings	1487:1494	arg1	basis					1472:1476	basis	1472:1476	basis	1472:1476	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	5	14	theme	mannose	666:672	arg1	removal					674:680	mannose removal	666:680	mannose removal	666:680	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	5	15	theme	ER-resident	902:912	arg1	oxidoreductase					914:927	an ER-resident oxidoreductase	899:927	an ER-resident oxidoreductase	899:927	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	5	15	theme	ER-resident	902:912	arg1	ERp46					892:896	ERp46	892:896	ERp46	892:896	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	2	16	from	folding	224:230	arg1	ER					279:280	ER	279:280	ER	279:280	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	2	16	from	folding	224:230	arg1	reticulum					268:276	the endoplasmic reticulum	252:276	the endoplasmic reticulum (ER)	252:281	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	4	17	theme	degradation-enhancing	571:591	arg1	EDEMs					622:626	EDEMs	622:626	EDEMs	622:626	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	4	17	theme	degradation-enhancing	571:591	arg1	proteins					612:619	ER degradation-enhancing α-mannosidase-like proteins	568:619	ER degradation-enhancing α-mannosidase-like proteins (EDEMs)	568:627	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	6	18	theme	EDEM3	1134:1138	arg1	domain					1154:1159	the EDEM3 α-mannosidase domain	1130:1159	the EDEM3 α-mannosidase domain	1130:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	7	19	theme	defined	1167:1173	arg1	system					1184:1189	a defined in vitro system	1165:1189	a defined in vitro system consisting of recombinant proteins purified from HEK293 cells	1165:1251	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	1	20	from	folding	144:150	arg1	cell					159:162	the cell	155:162	the cell	155:162	Protein folding in the cell is regulated by several quality-control mechanisms.
29784879	3	21	theme	mannose	413:419	arg1	trimming					421:428	mannose trimming	413:428	mannose trimming from N-glycans	413:443	In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins.
29784879	0	22	theme	protein	117:123	arg1	activity					61:68	the mannose-trimming activity	40:68	the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3)	40:133	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	5	23	from	analysis	797:804	arg1	glycoprotein					865:876	a misfolded glycoprotein	853:876	a misfolded glycoprotein	853:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	7	24	gly	glycoprotein	1335:1346	arg1	glycoprotein					1335:1346	the glycoprotein T-cell receptor α locus	1331:1370	the glycoprotein T-cell receptor α locus (TCRα)	1331:1377	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	2	25	from	lectins	344:350	arg1	pathway					392:398	the ER-associated degradation (ERAD) pathway	355:398	the ER-associated degradation (ERAD) pathway	355:398	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	3	26	gly	glycoproteins	482:494	arg1	glycoproteins					482:494	misfolded glycoproteins	472:494	misfolded glycoproteins	472:494	In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins.
29784879	8	27	gly	glycoproteins	1535:1547	arg1	glycoproteins					1535:1547	misfolded glycoproteins	1525:1547	misfolded glycoproteins	1525:1547	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	6	28	theme	cysteine	1076:1083	arg1	domain					1154:1159	the EDEM3 α-mannosidase domain	1130:1159	the EDEM3 α-mannosidase domain	1130:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	6	28	theme	cysteine	1076:1083	arg1	sites					1120:1124	the ERp46 redox-active sites	1097:1124	the ERp46 redox-active sites	1097:1124	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	6	28	theme	cysteine	1076:1083	arg1	residues					1085:1092	the cysteine residues	1072:1092	the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain	1072:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	7	29	theme	in	1175:1176	arg1	system					1184:1189	a defined in vitro system	1165:1189	a defined in vitro system consisting of recombinant proteins purified from HEK293 cells	1165:1251	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	8	30	theme	glycoproteins	1535:1547	arg1	disposal					1513:1520	disposal	1513:1520	disposal of misfolded glycoproteins through mannose trimming	1513:1572	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	2	31	theme	degradation	373:383	arg1	pathway					392:398	the ER-associated degradation (ERAD) pathway	355:398	the ER-associated degradation (ERAD) pathway	355:398	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	0	32	theme	ER-resident	0:10	arg1	protein					12:18	ER-resident protein 46	0:21	ER-resident protein 46 (ERp46)	0:29	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	0	32	theme	ER-resident	0:10	arg1	ERp46					24:28	ERp46	24:28	ERp46	24:28	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	4	33	theme	ER	547:548	arg1	mannosidase					550:560	ER mannosidase I	547:562	ER mannosidase I	547:562	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	4	33	theme	ER	547:548	arg1	mannosidases					501:512	The mannosidases	497:512	The mannosidases responsible for this process	497:541	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	2	34	theme	ER-associated	359:371	arg1	ERAD					386:389	ERAD	386:389	ERAD	386:389	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	2	34	theme	ER-associated	359:371	arg1	degradation					373:383	ER-associated degradation	359:383	the ER-associated degradation (ERAD) pathway	355:398	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	5	35	theme	EDEM3-mediated	809:822	arg1	activity					841:848	EDEM3-mediated mannose-trimming activity	809:848	EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein	809:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	8	36	theme	misfolded	1525:1533	arg1	glycoproteins					1535:1547	misfolded glycoproteins	1525:1547	misfolded glycoproteins	1525:1547	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	6	37	theme	domain	1154:1159	arg1	domain					1154:1159	the EDEM3 α-mannosidase domain	1130:1159	the EDEM3 α-mannosidase domain	1130:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	6	37	theme	domain	1154:1159	arg1	sites					1120:1124	the ERp46 redox-active sites	1097:1124	the ERp46 redox-active sites	1097:1124	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	6	37	theme	domain	1154:1159	arg1	residues					1085:1092	the cysteine residues	1072:1092	the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain	1072:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	1	38	theme	several	180:186	arg1	mechanisms					204:213	several quality-control mechanisms	180:213	several quality-control mechanisms	180:213	Protein folding in the cell is regulated by several quality-control mechanisms.
29784879	5	39	theme	mannose-trimming	824:839	arg1	activity					841:848	EDEM3-mediated mannose-trimming activity	809:848	EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein	809:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	8	40	theme	mannose	1557:1563	arg1	trimming					1565:1572	mannose trimming	1557:1572	mannose trimming	1557:1572	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	8	41	from	regulation	1613:1622	arg1	ER					1631:1632	the ER	1627:1632	the ER	1627:1632	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	6	42	theme	α-mannosidase	1140:1152	arg1	domain					1154:1159	the EDEM3 α-mannosidase domain	1130:1159	the EDEM3 α-mannosidase domain	1130:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	1	43	theme	quality-control	188:202	arg1	mechanisms					204:213	several quality-control mechanisms	180:213	several quality-control mechanisms	180:213	Protein folding in the cell is regulated by several quality-control mechanisms.
29784879	6	44	theme	redox-active	1107:1118	arg1	sites					1120:1124	the ERp46 redox-active sites	1097:1124	the ERp46 redox-active sites	1097:1124	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	3	45	theme	misfolded	472:480	arg1	glycoproteins					482:494	misfolded glycoproteins	472:494	misfolded glycoproteins	472:494	In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins.
29784879	5	46	dep	reconstituting	742:755	arg1	revealed					878:885	revealed	878:885	revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3	878:957	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	2	47	theme	glycoproteins	235:247	arg1	folding					224:230	Correct folding	216:230	Correct folding of glycoproteins in the endoplasmic reticulum (ER)	216:281	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	7	48	theme	covalent	1432:1439	arg1	interaction					1441:1451	a covalent interaction	1430:1451	a covalent interaction with EDEM3	1430:1462	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	2	49	gly	glycoproteins	235:247	arg1	glycoproteins					235:247	glycoproteins	235:247	glycoproteins	235:247	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	5	50	theme	misfolded	855:863	arg1	glycoprotein					865:876	a misfolded glycoprotein	853:876	a misfolded glycoprotein	853:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	4	51	theme	responsible	514:524	arg1	mannosidase					550:560	ER mannosidase I	547:562	ER mannosidase I	547:562	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	4	51	theme	responsible	514:524	arg1	mannosidases					501:512	The mannosidases	497:512	The mannosidases responsible for this process	497:541	The mannosidases responsible for this process are ER mannosidase I and ER degradation-enhancing α-mannosidase-like proteins (EDEMs).
29784879	5	52	theme	removal	674:680	arg1	mechanism					653:661	the molecular mechanism	639:661	the molecular mechanism of mannose removal by EDEMs	639:689	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	5	53	theme	mannosidase	757:767	arg1	activity					769:776	mannosidase activity	757:776	mannosidase activity	757:776	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	3	54	from	N-glycans	435:443	arg1	trimming					421:428	mannose trimming	413:428	mannose trimming from N-glycans	413:443	In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins.
29784879	2	55	theme	signals	333:339	arg1	recognition					311:321	the recognition	307:321	the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway	307:398	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	2	56	theme	Correct	216:222	arg1	folding					224:230	Correct folding	216:230	Correct folding of glycoproteins in the endoplasmic reticulum (ER)	216:281	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	5	57	from	activity	841:848	arg1	glycoprotein					865:876	a misfolded glycoprotein	853:876	a misfolded glycoprotein	853:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	2	58	theme	glycan	326:331	arg1	signals					333:339	glycan signals	326:339	glycan signals	326:339	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	7	59	with	interaction	1441:1451	arg1	EDEM3					1458:1462	EDEM3	1458:1462	EDEM3	1458:1462	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	60	theme	mannose-trimming	1258:1273	arg1	activity					1275:1282	the mannose-trimming activity	1254:1282	the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα),	1254:1378	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	3	61	from	crucial	448:454	arg1	mammals					404:410	mammals	404:410	mammals	404:410	In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins.
29784879	7	62	theme	recombinant	1205:1215	arg1	proteins					1217:1224	recombinant proteins	1205:1224	recombinant proteins purified from HEK293 cells	1205:1251	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	6	63	theme	redox	1000:1004	arg1	activity					1006:1013	the redox activity	996:1013	the redox activity of ERp46	996:1022	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	7	64	theme	EDEM3	1287:1291	arg1	activity					1275:1282	the mannose-trimming activity	1254:1282	the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα),	1254:1378	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	2	65	theme	endoplasmic	256:266	arg1	ER					279:280	ER	279:280	ER	279:280	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	2	65	theme	endoplasmic	256:266	arg1	reticulum					268:276	the endoplasmic reticulum	252:276	the endoplasmic reticulum (ER)	252:281	Correct folding of glycoproteins in the endoplasmic reticulum (ER) is tightly monitored by the recognition of glycan signals by lectins in the ER-associated degradation (ERAD) pathway.
29784879	3	66	from	mammals	404:410	arg1	crucial					448:454	crucial	448:454	crucial	448:454	In mammals, mannose trimming from N-glycans is crucial for disposal of misfolded glycoproteins.
29784879	6	67	theme	sites	1120:1124	arg1	domain					1154:1159	the EDEM3 α-mannosidase domain	1130:1159	the EDEM3 α-mannosidase domain	1130:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	6	67	theme	sites	1120:1124	arg1	sites					1120:1124	the ERp46 redox-active sites	1097:1124	the ERp46 redox-active sites	1097:1124	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	6	67	theme	sites	1120:1124	arg1	residues					1085:1092	the cysteine residues	1072:1092	the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain	1072:1159	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	8	68	theme	redox-mediated	1598:1611	arg1	regulation					1613:1622	redox-mediated regulation	1598:1622	redox-mediated regulation in the ER	1598:1632	On the basis of these findings, we propose that disposal of misfolded glycoproteins through mannose trimming is tightly connected to redox-mediated regulation in the ER.
29784879	7	69	theme	HEK293	1240:1245	arg1	cells					1247:1251	HEK293 cells	1240:1251	HEK293 cells	1240:1251	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	70	theme	model	1304:1308	arg1	locus					1366:1370	the glycoprotein T-cell receptor α locus	1331:1370	the glycoprotein T-cell receptor α locus (TCRα)	1331:1377	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	70	theme	model	1304:1308	arg1	substrate					1320:1328	the model misfolded substrate	1300:1328	the model misfolded substrate	1300:1328	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	71	theme	receptor	1355:1362	arg1	locus					1366:1370	the glycoprotein T-cell receptor α locus	1331:1370	the glycoprotein T-cell receptor α locus (TCRα)	1331:1377	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	71	theme	receptor	1355:1362	arg1	substrate					1320:1328	the model misfolded substrate	1300:1328	the model misfolded substrate	1300:1328	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	71	theme	receptor	1355:1362	arg1	TCRα					1373:1376	TCRα	1373:1376	TCRα	1373:1376	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	5	72	theme	activity	841:848	arg1	analysis					797:804	our analysis	793:804	our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein	793:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	1	73	theme	Protein	136:142	arg1	folding					144:150	Protein folding	136:150	Protein folding in the cell	136:162	Protein folding in the cell is regulated by several quality-control mechanisms.
29784879	7	74	theme	T-cell	1348:1353	arg1	locus					1366:1370	the glycoprotein T-cell receptor α locus	1331:1370	the glycoprotein T-cell receptor α locus (TCRα)	1331:1377	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	74	theme	T-cell	1348:1353	arg1	substrate					1320:1328	the model misfolded substrate	1300:1328	the model misfolded substrate	1300:1328	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	74	theme	T-cell	1348:1353	arg1	TCRα					1373:1376	TCRα	1373:1376	TCRα	1373:1376	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	0	75	theme	mannose-trimming	44:59	arg1	activity					61:68	the mannose-trimming activity	40:68	the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3)	40:133	ER-resident protein 46 (ERp46) triggers the mannose-trimming activity of ER degradation-enhancing α-mannosidase-like protein 3 (EDEM3).
29784879	7	76	theme	α	1364:1364	arg1	locus					1366:1370	the glycoprotein T-cell receptor α locus	1331:1370	the glycoprotein T-cell receptor α locus (TCRα)	1331:1377	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	76	theme	α	1364:1364	arg1	substrate					1320:1328	the model misfolded substrate	1300:1328	the model misfolded substrate	1300:1328	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	7	76	theme	α	1364:1364	arg1	TCRα					1373:1376	TCRα	1373:1376	TCRα	1373:1376	In a defined in vitro system consisting of recombinant proteins purified from HEK293 cells, the mannose-trimming activity of EDEM3 toward the model misfolded substrate, the glycoprotein T-cell receptor α locus (TCRα), was reconstituted only when ERp46 had established a covalent interaction with EDEM3.
29784879	5	77	from	glycoprotein	865:876	arg1	analysis					797:804	our analysis	793:804	our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein	793:876	However, the molecular mechanism of mannose removal by EDEMs remains unclear, partly owing to the difficulty of reconstituting mannosidase activity in vitro Here, our analysis of EDEM3-mediated mannose-trimming activity on a misfolded glycoprotein revealed that ERp46, an ER-resident oxidoreductase, associates stably with EDEM3.
29784879	6	78	theme	ERp46	1101:1105	arg1	sites					1120:1124	the ERp46 redox-active sites	1097:1124	the ERp46 redox-active sites	1097:1124	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29784879	6	79	theme	ERp46	1018:1022	arg1	activity					1006:1013	the redox activity	996:1013	the redox activity of ERp46	996:1022	This interaction, which depended on the redox activity of ERp46, involved formation of a disulfide bond between the cysteine residues of the ERp46 redox-active sites and the EDEM3 α-mannosidase domain.
29933399	9	0	theme	genes	1845:1849	arg1	set					1824:1826	a narrower set	1813:1826	a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells	1813:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	9	0	theme	genes	1845:1849	arg1	genes					1845:1849	IGH/IGK/IGL-V genes	1831:1849	IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells	1831:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	6	1	theme	cell	927:930	arg1	lineages					932:939	clonal B cell lineages	918:939	clonal B cell lineages	918:939	These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization.
29933399	10	2	theme	B	2032:2032	arg1	lineages					2039:2046	particular B cell lineages	2021:2046	particular B cell lineages	2021:2046	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	4	3	theme	notable	578:584	arg1	exceptions					586:595	a few notable exceptions	572:595	a few notable exceptions	572:595	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	1	4	attach	isolated	145:152	arg1	subjects					168:175	infected subjects	159:175	infected subjects	159:175	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	1	4	attach	isolated	145:152	arg2	bNAbs					138:142	bNAbs	138:142	bNAbs	138:142	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	1	4	attach	isolated	145:152	arg2	antibodies					126:135	Broadly neutralizing HIV-1 antibodies	99:135	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects	99:175	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	4	5	with	bNAbs	560:564	arg1	exceptions					586:595	a few notable exceptions	572:595	a few notable exceptions	572:595	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	6	6	theme	clonal	918:923	arg1	lineages					932:939	clonal B cell lineages	918:939	clonal B cell lineages	918:939	These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization.
29933399	10	7	theme	lineages	2039:2046	arg1	expansion					2008:2016	the expansion	2004:2016	the expansion of particular B cell lineages	2004:2046	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	9	8	theme	small	1870:1874	arg1	fraction					1876:1883	a small fraction	1868:1883	a small fraction (0.003-0.02%) of total B cells	1868:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	9	8	theme	small	1870:1874	arg1	%					1896:1896	0.003-0.02%	1886:1896	0.003-0.02%	1886:1896	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	8	9	theme	lymph	1260:1264	arg1	nodes					1266:1270	lymph nodes	1260:1270	lymph nodes	1260:1270	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	9	theme	lymph	1260:1264	arg1	periphery					1249:1257	the periphery	1245:1257	the periphery	1245:1257	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	7	10	theme	antibodies	1124:1133	arg1	development					1092:1102	the development	1088:1102	the development of non-neutralizing antibodies	1088:1133	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	8	11	theme	high-throughput	1202:1216	arg1	analysis					1231:1238	high-throughput BCR sequence analysis	1202:1238	high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods,	1202:1359	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	12	theme	sequence	1222:1229	arg1	analysis					1231:1238	high-throughput BCR sequence analysis	1202:1238	high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods,	1202:1359	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	3	13	theme	HIV-1	288:292	arg1	Env					317:319	Env	317:319	Env	317:319	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	13	theme	HIV-1	288:292	arg1	target					340:345	the sole viral target	325:345	the sole viral target of bnAbs	325:354	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	13	theme	HIV-1	288:292	arg1	glycoprotein					303:314	The HIV-1 envelope glycoprotein	284:314	The HIV-1 envelope glycoprotein (Env)	284:320	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	8	14	theme	marrow	1281:1286	arg1	methods					1352:1358	bone marrow, as well as B cell- and antibody-isolation and characterization methods	1276:1358	bone marrow, as well as B cell- and antibody-isolation and characterization methods	1276:1358	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	14	theme	marrow	1281:1286	arg1	periphery					1249:1257	the periphery	1245:1257	the periphery	1245:1257	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	10	15	theme	cells	2125:2129	arg1	expansion					2112:2120	the expansion	2108:2120	the expansion of cells expressing particular B cell receptors	2108:2168	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	1	16	theme	animal	209:214	arg1	models					216:221	animal models	209:221	animal models	209:221	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	10	17	theme	new	1936:1938	arg1	information					1940:1950	new information	1936:1950	new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages	1936:2046	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	7	18	theme	B	1048:1048	arg1	lineages					1055:1062	particular B cell lineages	1037:1062	particular B cell lineages	1037:1062	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	9	19	theme	B	1908:1908	arg1	cells					1910:1914	total B cells	1902:1914	total B cells	1902:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	5	20	theme	intensive	663:671	arg1	efforts					673:679	intensive efforts	663:679	intensive efforts	663:679	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	8	21	theme	cell-	1302:1306	arg1	methods					1352:1358	bone marrow, as well as B cell- and antibody-isolation and characterization methods	1276:1358	bone marrow, as well as B cell- and antibody-isolation and characterization methods	1276:1358	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	21	theme	cell-	1302:1306	arg1	periphery					1249:1257	the periphery	1245:1257	the periphery	1245:1257	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	10	22	theme	Env	1959:1961	arg1	differences					1973:1983	Env antigenic differences	1959:1983	Env antigenic differences	1959:1983	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	3	23	theme	sole	329:332	arg1	glycoprotein					303:314	The HIV-1 envelope glycoprotein	284:314	The HIV-1 envelope glycoprotein (Env)	284:320	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	23	theme	sole	329:332	arg1	target					340:345	the sole viral target	325:345	the sole viral target of bnAbs	325:354	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	8	24	theme	clade	1473:1477	arg1	426c					1489:1492	the clade C HIV Env 426c	1469:1492	the clade C HIV Env 426c	1469:1492	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	25	theme	antibody-isolation	1312:1329	arg1	methods					1352:1358	bone marrow, as well as B cell- and antibody-isolation and characterization methods	1276:1358	bone marrow, as well as B cell- and antibody-isolation and characterization methods	1276:1358	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	25	theme	antibody-isolation	1312:1329	arg1	periphery					1249:1257	the periphery	1245:1257	the periphery	1245:1257	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	0	26	theme	envelope	57:64	arg1	immunization					66:77	recombinant HIV-1 envelope immunization	39:77	recombinant HIV-1 envelope immunization of rhesus macaques	39:96	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	8	27	theme	HIV	1481:1483	arg1	426c					1489:1492	the clade C HIV Env 426c	1469:1492	the clade C HIV Env 426c	1469:1492	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	10	28	theme	B	2153:2153	arg1	receptors					2160:2168	particular B cell receptors	2142:2168	particular B cell receptors	2142:2168	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	8	29	from	periphery	1249:1257	arg1	analysis					1231:1238	high-throughput BCR sequence analysis	1202:1238	high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods,	1202:1359	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	7	30	theme	current	991:997	arg1	understanding					999:1011	our current understanding	987:1011	our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies	987:1133	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	1	31	theme	infected	159:166	arg1	subjects					168:175	infected subjects	159:175	infected subjects	159:175	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	3	32	theme	bnAbs	350:354	arg1	glycoprotein					303:314	The HIV-1 envelope glycoprotein	284:314	The HIV-1 envelope glycoprotein (Env)	284:320	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	32	theme	bnAbs	350:354	arg1	target					340:345	the sole viral target	325:345	the sole viral target of bnAbs	325:354	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	8	33	theme	426c	1489:1492	arg1	forms					1460:1464	two forms	1456:1464	two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites	1456:1660	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	34	dep	analysis	1180:1187	arg1	addition					1156:1163	addition	1156:1163	addition	1156:1163	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	0	35	theme	macaques	89:96	arg1	immunization					66:77	recombinant HIV-1 envelope immunization	39:77	recombinant HIV-1 envelope immunization of rhesus macaques	39:96	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	8	36	dep	domains	1594:1600	arg1	3					1611:1611	3	1611:1611	3	1611:1611	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	36	dep	domains	1594:1600	arg1	1					1602:1602	1	1602:1602	1	1602:1602	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	4	37	theme	various	457:463	arg1	species					472:478	various animal species	457:478	various animal species	457:478	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	5	38	theme	antibodies	739:748	arg1	specificities					709:721	the binding specificities	697:721	the binding specificities of the elicited antibodies;	697:749	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	8	39	theme	great	1375:1379	arg1	detail					1381:1386	great detail	1375:1386	great detail	1375:1386	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	0	40	theme	B	0:0	arg1	lineage					14:20	B cell clonal lineage	0:20	B cell clonal lineage	0:20	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	8	41	link	N-linked	1633:1640	arg1	sites					1656:1660	three conserved N-linked glycosylation sites	1617:1660	three conserved N-linked glycosylation sites	1617:1660	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	7	42	theme	non-neutralizing	1107:1122	arg1	antibodies					1124:1133	non-neutralizing antibodies	1107:1133	non-neutralizing antibodies	1107:1133	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	9	43	theme	restricted	1778:1787	arg1	expansion					1789:1797	a more restricted expansion	1771:1797	a more restricted expansion of B cells	1771:1808	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	8	44	theme	length	1521:1526	arg1	portion					1542:1548	the full length extracellular portion	1512:1548	the full length extracellular portion of Env	1512:1555	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	0	45	theme	clonal	7:12	arg1	lineage					14:20	B cell clonal lineage	0:20	B cell clonal lineage	0:20	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	1	46	theme	neutralizing	107:118	arg1	bNAbs					138:142	bNAbs	138:142	bNAbs	138:142	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	1	46	theme	neutralizing	107:118	arg1	antibodies					126:135	Broadly neutralizing HIV-1 antibodies	99:135	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects	99:175	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	8	47	dep	forms	1460:1464	arg1	one					1495:1497	one	1495:1497	one	1495:1497	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	9	48	theme	B	1802:1802	arg1	cells					1804:1808	B cells	1802:1808	B cells	1802:1808	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	9	49	theme	cells	1804:1808	arg1	expansion					1789:1797	a more restricted expansion	1771:1797	a more restricted expansion of B cells	1771:1808	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	8	50	theme	Env	1553:1555	arg1	portion					1542:1548	the full length extracellular portion	1512:1548	the full length extracellular portion of Env	1512:1555	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	51	theme	antibody	1403:1410	arg1	responses					1412:1420	the B cell and antibody responses	1388:1420	responses	1412:1420	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	5	52	theme	monoclonal	799:808	arg1	antibody					810:817	monoclonal antibody	799:817	monoclonal antibody	799:817	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	10	53	theme	particular	2021:2030	arg1	lineages					2039:2046	particular B cell lineages	2021:2046	particular B cell lineages	2021:2046	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	4	54	theme	neutralizing	528:539	arg1	antibodies					541:550	binding and autologous neutralizing antibodies	505:550	antibodies	541:550	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	6	55	dep	ontogenies	903:912	arg1	the					899:901	the	899:901	the	899:901	These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization.
29933399	8	56	theme	non-human	1434:1442	arg1	primates					1444:1451	non-human primates	1434:1451	non-human primates	1434:1451	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	9	57	theme	IGH/IGK/IGL-V	1831:1843	arg1	genes					1845:1849	IGH/IGK/IGL-V genes	1831:1849	IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells	1831:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	8	58	theme	variable	1585:1592	arg1	domains					1594:1600	the variable domains 1, 2 and 3	1581:1611	the variable domains 1, 2 and 3	1581:1611	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	59	theme	N-linked	1633:1640	arg1	sites					1656:1660	three conserved N-linked glycosylation sites	1617:1660	three conserved N-linked glycosylation sites	1617:1660	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	3	60	gly	glycoprotein	303:314	arg1	Env					317:319	Env	317:319	Env	317:319	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	60	gly	glycoprotein	303:314	arg1	target					340:345	the sole viral target	325:345	the sole viral target of bnAbs	325:354	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	60	gly	glycoprotein	303:314	arg1	glycoprotein					303:314	The HIV-1 envelope glycoprotein	284:314	The HIV-1 envelope glycoprotein (Env)	284:320	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	10	61	theme	cell	2034:2037	arg1	lineages					2039:2046	particular B cell lineages	2021:2046	particular B cell lineages	2021:2046	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	8	62	theme	serological	1168:1178	arg1	analysis					1180:1187	serological analysis	1168:1187	serological analysis	1168:1187	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	6	63	theme	B	925:925	arg1	lineages					932:939	clonal B cell lineages	918:939	clonal B cell lineages	918:939	These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization.
29933399	4	64	theme	few	574:576	arg1	exceptions					586:595	a few notable exceptions	572:595	a few notable exceptions	572:595	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	5	65	theme	underlying	603:612	arg1	reasons					614:620	The underlying reasons	599:620	The underlying reasons for this	599:629	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	0	66	theme	recombinant	39:49	arg1	immunization					66:77	recombinant HIV-1 envelope immunization	39:77	recombinant HIV-1 envelope immunization of rhesus macaques	39:96	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	8	67	gly	glycosylation	1642:1654	arg2	sites					1656:1660	three conserved N-linked glycosylation sites	1617:1660	three conserved N-linked glycosylation sites	1617:1660	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	67	gly	glycosylation	1642:1654	arg2	three					1617:1621	three	1617:1621	three	1617:1621	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	10	68	theme	immunogen-design	2061:2076	arg1	efforts					2078:2084	immunogen-design efforts	2061:2084	immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors	2061:2168	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	6	69	from	information	884:894	arg1	lineages					932:939	clonal B cell lineages	918:939	clonal B cell lineages	918:939	These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization.
29933399	6	69	from	information	884:894	arg1	ontogenies					903:912	ontogenies	903:912	ontogenies	903:912	These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization.
29933399	1	70	theme	protective	185:194	arg1	potential					196:204	protective potential	185:204	protective potential	185:204	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	5	71	dep	methodologies	781:793	arg1	isolation					819:827	isolation	819:827	isolation	819:827	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	5	71	dep	methodologies	781:793	arg1	methodologies					781:793	serologic methodologies	771:793	serologic methodologies	771:793	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	5	71	dep	methodologies	781:793	arg1	characterization					833:848	characterization	833:848	characterization	833:848	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	8	72	theme	BCR	1218:1220	arg1	analysis					1231:1238	high-throughput BCR sequence analysis	1202:1238	high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods,	1202:1359	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	3	73	theme	envelope	294:301	arg1	Env					317:319	Env	317:319	Env	317:319	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	73	theme	envelope	294:301	arg1	target					340:345	the sole viral target	325:345	the sole viral target of bnAbs	325:354	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	73	theme	envelope	294:301	arg1	glycoprotein					303:314	The HIV-1 envelope glycoprotein	284:314	The HIV-1 envelope glycoprotein (Env)	284:320	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	7	74	attach	linked	1078:1083	arg2	understanding					999:1011	our current understanding	987:1011	our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies	987:1133	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	7	74	attach	linked	1078:1083	arg1	development					1092:1102	the development	1088:1102	the development of non-neutralizing antibodies	1088:1133	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	7	74	attach	linked	1078:1083	arg2	expansion					1024:1032	the expansion	1020:1032	the expansion of particular B cell lineages by Env	1020:1069	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	8	75	theme	bone	1276:1279	arg1	marrow					1281:1286	bone marrow	1276:1286	bone marrow	1276:1286	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	5	76	theme	binding	701:707	arg1	specificities					709:721	the binding specificities	697:721	the binding specificities of the elicited antibodies;	697:749	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	9	77	theme	total	1902:1906	arg1	cells					1910:1914	total B cells	1902:1914	total B cells	1902:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	9	78	theme	neutralizing	1732:1743	arg1	antibodies					1745:1754	neutralizing antibodies	1732:1754	neutralizing antibodies	1732:1754	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	7	79	theme	cell	1050:1053	arg1	lineages					1055:1062	particular B cell lineages	1037:1062	particular B cell lineages	1037:1062	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	1	80	theme	HIV-1	120:124	arg1	bNAbs					138:142	bNAbs	138:142	bNAbs	138:142	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	1	80	theme	HIV-1	120:124	arg1	antibodies					126:135	Broadly neutralizing HIV-1 antibodies	99:135	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects	99:175	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	9	81	theme	cells	1910:1914	arg1	fraction					1876:1883	a small fraction	1868:1883	a small fraction (0.003-0.02%) of total B cells	1868:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	9	81	theme	cells	1910:1914	arg1	%					1896:1896	0.003-0.02%	1886:1896	0.003-0.02%	1886:1896	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	7	82	theme	lineages	1055:1062	arg1	expansion					1024:1032	the expansion	1020:1032	the expansion of particular B cell lineages by Env	1020:1069	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	7	83	theme	particular	1037:1046	arg1	lineages					1055:1062	particular B cell lineages	1037:1062	particular B cell lineages	1037:1062	Thus, our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited.
29933399	8	84	theme	C	1479:1479	arg1	426c					1489:1492	the clade C HIV Env 426c	1469:1492	the clade C HIV Env 426c	1469:1492	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	85	theme	B	1300:1300	arg1	cell-					1302:1306	B cell-	1300:1306	B cell-	1300:1306	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	3	86	theme	viral	334:338	arg1	glycoprotein					303:314	The HIV-1 envelope glycoprotein	284:314	The HIV-1 envelope glycoprotein (Env)	284:320	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	86	theme	viral	334:338	arg1	target					340:345	the sole viral target	325:345	the sole viral target of bnAbs	325:354	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	8	87	theme	Env	1485:1487	arg1	426c					1489:1492	the clade C HIV Env 426c	1469:1492	the clade C HIV Env 426c	1469:1492	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	10	88	theme	cell	2155:2158	arg1	receptors					2160:2168	particular B cell receptors	2142:2168	particular B cell receptors	2142:2168	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	0	89	theme	rhesus	82:87	arg1	macaques					89:96	rhesus macaques	82:96	rhesus macaques	82:96	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	4	90	theme	Env-based	419:427	arg1	immunogens					429:438	Env-based immunogens	419:438	Env-based immunogens tested so far in various animal species and humans	419:489	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	4	91	theme	binding	505:511	arg1	antibodies					541:550	binding and autologous neutralizing antibodies	505:550	antibodies	541:550	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	4	92	theme	animal	465:470	arg1	species					472:478	various animal species	457:478	various animal species	457:478	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	10	93	theme	antigenic	1963:1971	arg1	differences					1973:1983	Env antigenic differences	1959:1983	Env antigenic differences	1959:1983	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	5	94	theme	elicited	730:737	arg1	antibodies					739:748	the elicited antibodies	726:748	the elicited antibodies	726:748	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	8	95	theme	full	1516:1519	arg1	portion					1542:1548	the full length extracellular portion	1512:1548	the full length extracellular portion of Env	1512:1555	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	0	96	theme	cell	2:5	arg1	lineage					14:20	B cell clonal lineage	0:20	B cell clonal lineage	0:20	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	8	97	theme	extracellular	1528:1540	arg1	portion					1542:1548	the full length extracellular portion	1512:1548	the full length extracellular portion of Env	1512:1555	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	1	98	theme	Broadly	99:105	arg1	bNAbs					138:142	bNAbs	138:142	bNAbs	138:142	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	1	98	theme	Broadly	99:105	arg1	antibodies					126:135	Broadly neutralizing HIV-1 antibodies	99:135	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects	99:175	Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models.
29933399	5	99	theme	serologic	771:779	arg1	isolation					819:827	isolation	819:827	isolation	819:827	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	5	99	theme	serologic	771:779	arg1	methodologies					781:793	serologic methodologies	771:793	serologic methodologies	771:793	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	5	99	theme	serologic	771:779	arg1	characterization					833:848	characterization	833:848	characterization	833:848	The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization.
29933399	3	100	theme	non-neutralizing	390:405	arg1	binding					381:387	binding	381:387	binding	381:387	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	3	100	theme	non-neutralizing	390:405	arg1	antibodies					407:416	non-neutralizing antibodies	390:416	non-neutralizing antibodies	390:416	The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies.
29933399	4	101	theme	autologous	517:526	arg1	antibodies					541:550	binding and autologous neutralizing antibodies	505:550	antibodies	541:550	Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions).
29933399	8	102	theme	B	1392:1392	arg1	cell					1394:1397	the B cell and antibody responses	1388:1420	cell	1394:1397	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	0	103	theme	HIV-1	51:55	arg1	immunization					66:77	recombinant HIV-1 envelope immunization	39:77	recombinant HIV-1 envelope immunization of rhesus macaques	39:96	B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
29933399	6	104	theme	limited	876:882	arg1	information					884:894	limited information	876:894	limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization	876:978	These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization.
29933399	9	105	theme	narrower	1815:1822	arg1	set					1824:1826	a narrower set	1813:1826	a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells	1813:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	9	105	theme	narrower	1815:1822	arg1	genes					1845:1849	IGH/IGK/IGL-V genes	1831:1849	IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells	1831:1914	The two forms were equally immunogenic, but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02%) of total B cells.
29933399	10	106	theme	particular	2142:2151	arg1	receptors					2160:2168	particular B cell receptors	2142:2168	particular B cell receptors	2142:2168	Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
29933399	8	107	theme	conserved	1623:1631	arg1	sites					1656:1660	three conserved N-linked glycosylation sites	1617:1660	three conserved N-linked glycosylation sites	1617:1660	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29933399	8	108	theme	glycosylation	1642:1654	arg1	sites					1656:1660	three conserved N-linked glycosylation sites	1617:1660	three conserved N-linked glycosylation sites	1617:1660	Here, in addition to serological analysis, we employed high-throughput BCR sequence analysis from the periphery, lymph nodes and bone marrow, as well as B cell- and antibody-isolation and characterization methods, to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1, 2 and 3 and three conserved N-linked glycosylation sites.
29045410	2	0	theme	host	401:404	arg1	immunity					406:413	host immunity	401:413	host immunity	401:413	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	0	1	from	rates	13:17	arg1	B					55:55	HIV-1 subtype B	41:55	HIV-1 subtype B	41:55	Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
29045410	5	2	theme	nucleotide	975:984	arg1	rates					999:1003	ensuing nucleotide substitution rates	967:1003	ensuing nucleotide substitution rates	967:1003	No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein.
29045410	1	3	theme	HIV	133:135	arg1	infection					137:145	HIV infection	133:145	HIV infection	133:145	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	7	4	theme	immune	1505:1510	arg1	system					1512:1517	immune system composition and sensitivities	1505:1547	system	1512:1517	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	2	5	from	evolution	352:360	arg1	majority					326:333	the vast majority	317:333	the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences,	317:455	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	7	6	from	differences	1450:1460	arg1	progression					1479:1489	HIV-1 disease progression	1465:1489	HIV-1 disease progression attributed to immune system composition and sensitivities	1465:1547	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	1	7	theme	infection	137:145	arg1	course					123:128	the course	119:128	the course of HIV infection	119:145	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	7	8	theme	global	1590:1595	arg1	patterns					1597:1604	global patterns	1590:1604	global patterns	1590:1604	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	6	9	theme	P	1211:1211	arg1	0.017					1215:1219	P = 0.017	1211:1219	P = 0.017	1211:1219	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	6	9	theme	P	1211:1211	arg1	200					1206:1208	200	1206:1208	200	1206:1208	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	0	10	from	Patterns	0:7	arg1	B					55:55	HIV-1 subtype B	41:55	HIV-1 subtype B	41:55	Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
29045410	3	11	from	participants	645:656	arg1	years					582:586	the first 6-11 years	567:586	the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	567:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	4	12	with	homogenous	890:899	arg1	differences					909:919	no differences	906:919	no differences in diversity between sexes	906:946	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	6	13	theme	changes	1366:1372	arg1	majority					1354:1361	the majority	1350:1361	the majority of changes	1350:1372	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	3	14	theme	antiretroviral	691:704	arg1	therapy					706:712	combination antiretroviral therapy	679:712	combination antiretroviral therapy (ART)	679:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	3	14	theme	antiretroviral	691:704	arg1	ART					715:717	ART	715:717	ART	715:717	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	3	15	theme	Women	608:612	arg1	participants					645:656	8 Women's Interagency HIV Study (WIHS) participants	606:656	8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	606:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	3	15	theme	Women	608:612	arg1	WIHS					639:642	WIHS	639:642	WIHS	639:642	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	4	16	theme	similar	742:748	arg1	data					750:753	similar data	742:753	similar data previously collected from men	742:783	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	6	17	dep	increased	1290:1298	arg1	followed					1311:1318	followed	1311:1318	followed	1311:1318	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	4	18	from	differences	909:919	arg1	diversity					924:932	diversity	924:932	diversity between sexes	924:946	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	6	19	from	diversity	1113:1121	arg1	env-gp120					1126:1134	env-gp120	1126:1134	env-gp120 in women	1126:1143	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	7	20	theme	patterns	1597:1604	arg1	latter					1630:1635	latter	1630:1635	latter	1630:1635	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	4	21	theme	HIV-1	817:821	arg1	subtype					823:829	HIV-1 subtype	817:829	HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes	817:946	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	5	22	theme	ensuing	967:973	arg1	rates					999:1003	ensuing nucleotide substitution rates	967:1003	ensuing nucleotide substitution rates	967:1003	No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein.
29045410	6	23	from	env-gp120	1126:1134	arg1	women					1139:1143	women	1139:1143	women	1139:1143	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	2	24	theme	vast	321:324	arg1	majority					326:333	the vast majority	317:333	the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences,	317:455	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	6	25	theme	sites	1274:1278	arg1	number					1231:1236	the number	1227:1236	the number of predicted N-linked glycosylation sites	1227:1278	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	4	26	theme	virus	840:844	arg1	populations					846:856	B. Early virus populations	831:856	B. Early virus populations in men and women	831:873	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	6	27	theme	peak	1108:1111	arg1	diversity					1113:1121	peak diversity	1108:1121	peak diversity in env-gp120 in women	1108:1143	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	5	28	theme	female	1028:1033	arg1	cohorts					1044:1050	the female and male cohorts	1024:1050	the female and male cohorts studied herein	1024:1065	No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein.
29045410	6	29	gly	glycosylation	1260:1272	arg2	sites					1274:1278	predicted N-linked glycosylation sites	1241:1278	predicted N-linked glycosylation sites	1241:1278	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	2	30	attach	derived	466:472	arg2	majority					326:333	the vast majority	317:333	the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences,	317:455	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	2	30	attach	derived	466:472	arg1	men					479:481	men	479:481	men	479:481	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	1	31	theme	untreated	153:161	arg1	women					163:167	untreated women	153:167	untreated women having lower viral loads compared to their male counterparts	153:228	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	6	32	theme	glycosylation	1260:1272	arg1	sites					1274:1278	predicted N-linked glycosylation sites	1241:1278	predicted N-linked glycosylation sites	1241:1278	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	5	33	theme	male	1039:1042	arg1	cohorts					1044:1050	the female and male cohorts	1024:1050	the female and male cohorts studied herein	1024:1065	No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein.
29045410	1	34	contain	have	265:268	arg1	women					259:263	women	259:263	women	259:263	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	1	34	contain	have	265:268	arg2	rate					279:282	a higher rate	270:282	a higher rate of progression to AIDS	270:305	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	7	35	theme	viral	1609:1613	arg1	evolution					1615:1623	viral evolution	1609:1623	viral evolution	1609:1623	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	3	36	theme	evolution	546:554	arg1	analysis					510:517	an intensive analysis	497:517	an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	497:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	5	37	from	differences	952:962	arg1	rates					999:1003	ensuing nucleotide substitution rates	967:1003	ensuing nucleotide substitution rates	967:1003	No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein.
29045410	1	38	theme	given	241:245	arg1	load					253:256	a given viral load	239:256	a given viral load	239:256	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	4	39	dep	subtype	823:829	arg1	homogenous					890:899	homogenous	890:899	homogenous	890:899	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	6	40	theme	=	1213:1213	arg1	0.017					1215:1219	P = 0.017	1211:1219	P = 0.017	1211:1219	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	6	40	theme	=	1213:1213	arg1	200					1206:1208	200	1206:1208	200	1206:1208	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	2	41	theme	viral	346:350	arg1	evolution					352:360	viral evolution	346:360	viral evolution	346:360	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	2	41	theme	viral	346:350	arg1	process					365:371	a process	363:371	a process that is clearly impacted by host immunity and could be impacted by sex differences	363:454	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	6	42	theme	predicted	1241:1249	arg1	sites					1274:1278	predicted N-linked glycosylation sites	1241:1278	predicted N-linked glycosylation sites	1241:1278	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	1	43	theme	viral	247:251	arg1	load					253:256	a given viral load	239:256	a given viral load	239:256	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	6	44	theme	cell	1189:1192	arg1	count					1194:1198	CD4+ cell count	1184:1198	CD4+ cell count below 200 (P = 0.017)	1184:1220	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	3	45	theme	env-gp120	536:544	arg1	evolution					546:554	env-gp120 evolution	536:554	env-gp120 evolution	536:554	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	1	46	theme	Biological	85:94	arg1	differences					100:110	Biological sex differences	85:110	Biological sex differences	85:110	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	7	47	theme	HIV-1	1465:1469	arg1	progression					1479:1489	HIV-1 disease progression	1465:1489	HIV-1 disease progression attributed to immune system composition and sensitivities	1465:1547	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	1	48	theme	lower	176:180	arg1	loads					188:192	lower viral loads	176:192	lower viral loads	176:192	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	0	49	theme	evolution	28:36	arg1	rates					13:17	rates	13:17	rates	13:17	Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
29045410	0	49	theme	evolution	28:36	arg1	Patterns					0:7	Patterns	0:7	Patterns	0:7	Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
29045410	3	50	theme	HIV	628:630	arg1	Study					632:636	Interagency HIV Study	616:636	8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	606:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	6	51	theme	CD4+	1184:1187	arg1	count					1194:1198	CD4+ cell count	1184:1198	CD4+ cell count below 200 (P = 0.017)	1184:1220	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	2	52	theme	data	338:341	arg1	majority					326:333	the vast majority	317:333	the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences,	317:455	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	7	53	theme	disease	1471:1477	arg1	progression					1479:1489	HIV-1 disease progression	1465:1489	HIV-1 disease progression attributed to immune system composition and sensitivities	1465:1547	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	1	54	theme	viral	182:186	arg1	loads					188:192	lower viral loads	176:192	lower viral loads	176:192	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	0	55	theme	viral	22:26	arg1	evolution					28:36	viral evolution	22:36	viral evolution	22:36	Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
29045410	2	56	theme	sex	440:442	arg1	differences					444:454	sex differences	440:454	sex differences	440:454	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	3	57	theme	gag	528:530	arg1	analysis					510:517	an intensive analysis	497:517	an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	497:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	6	58	theme	N-linked	1251:1258	arg1	sites					1274:1278	predicted N-linked glycosylation sites	1241:1278	predicted N-linked glycosylation sites	1241:1278	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	6	59	link	N-linked	1251:1258	arg1	sites					1274:1278	predicted N-linked glycosylation sites	1241:1278	predicted N-linked glycosylation sites	1241:1278	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	0	60	theme	HIV-1	41:45	arg1	B					55:55	HIV-1 subtype B	41:55	HIV-1 subtype B	41:55	Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
29045410	4	61	theme	B.	831:832	arg1	populations					846:856	B. Early virus populations	831:856	B. Early virus populations in men and women	831:873	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	7	62	theme	sex	1446:1448	arg1	differences					1450:1460	the sex differences	1442:1460	the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities	1442:1547	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	1	63	theme	sex	96:98	arg1	differences					100:110	Biological sex differences	85:110	Biological sex differences	85:110	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	1	64	theme	progression	287:297	arg1	rate					279:282	a higher rate	270:282	a higher rate of progression to AIDS	270:305	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	3	65	dep	Women	608:612	arg1	Study					632:636	Interagency HIV Study	616:636	8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	606:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	5	66	theme	substitution	986:997	arg1	rates					999:1003	ensuing nucleotide substitution rates	967:1003	ensuing nucleotide substitution rates	967:1003	No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein.
29045410	2	67	from	majority	326:333	arg1	evolution					352:360	viral evolution	346:360	viral evolution	346:360	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	2	67	from	majority	326:333	arg1	process					365:371	a process	363:371	a process that is clearly impacted by host immunity and could be impacted by sex differences	363:454	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	7	68	dep	system	1512:1517	arg1	composition					1519:1529	composition	1519:1529	composition	1519:1529	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	3	69	theme	first	571:575	arg1	years					582:586	the first 6-11 years	567:586	the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	567:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	6	70	theme	V1-V2	1391:1395	arg1	region					1397:1402	the V1-V2 region	1387:1402	the V1-V2 region	1387:1402	As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region.
29045410	3	71	theme	Interagency	616:626	arg1	Study					632:636	Interagency HIV Study	616:636	8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	606:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	7	72	theme	evolution	1615:1623	arg1	patterns					1597:1604	global patterns	1590:1604	global patterns	1590:1604	These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.
29045410	4	73	from	populations	846:856	arg1	women					869:873	women	869:873	women	869:873	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	4	73	from	populations	846:856	arg1	men					861:863	men	861:863	men	861:863	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	3	74	theme	HIV-1	522:526	arg1	gag					528:530	HIV-1 gag	522:530	HIV-1 gag	522:530	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	2	75	from	data	338:341	arg1	evolution					352:360	viral evolution	346:360	viral evolution	346:360	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	2	75	from	data	338:341	arg1	process					365:371	a process	363:371	a process that is clearly impacted by host immunity and could be impacted by sex differences	363:454	However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men.
29045410	3	76	theme	combination	679:689	arg1	therapy					706:712	combination antiretroviral therapy	679:712	combination antiretroviral therapy (ART)	679:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	3	76	theme	combination	679:689	arg1	ART					715:717	ART	715:717	ART	715:717	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	4	77	theme	Early	834:838	arg1	populations					846:856	B. Early virus populations	831:856	B. Early virus populations in men and women	831:873	This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes.
29045410	1	78	contain	having	169:174	arg2	loads					188:192	lower viral loads	176:192	lower viral loads	176:192	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	1	78	contain	having	169:174	arg1	women					163:167	untreated women	153:167	untreated women having lower viral loads compared to their male counterparts	153:228	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	3	79	theme	intensive	500:508	arg1	analysis					510:517	an intensive analysis	497:517	an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	497:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	0	80	theme	subtype	47:53	arg1	B					55:55	HIV-1 subtype B	41:55	HIV-1 subtype B	41:55	Patterns and rates of viral evolution in HIV-1 subtype B infected females and males.
29045410	1	81	theme	higher	272:277	arg1	rate					279:282	a higher rate	270:282	a higher rate of progression to AIDS	270:305	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
29045410	3	82	theme	infection	591:599	arg1	years					582:586	the first 6-11 years	567:586	the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART)	567:718	We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART).
29045410	1	83	theme	male	212:215	arg1	counterparts					217:228	their male counterparts	206:228	their male counterparts	206:228	Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS.
27643667	5	0	used	used	347:350	arg2	We					344:345	We	344:345	We	344:345	METHODS: We used eight glycosidases to remove different glycans on MPO separately.
27643667	3	1	theme	glycosylation	217:229	arg1	sites					231:235	five N-linked glycosylation sites	203:235	five N-linked glycosylation sites	203:235	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	4	2	theme	MPO	314:316	arg1	functions					301:309	the functions	297:309	the functions of MPO	297:316	The effect of glycosylation pattern to the functions of MPO is barely known.
27643667	11	3	theme	innermost	1457:1465	arg1	GlcNAc					1467:1472	innermost GlcNAc	1457:1472	innermost GlcNAc	1457:1472	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001).
27643667	6	4	theme	reversing	503:511	arg1	effect					513:518	the reversing effect	499:518	the reversing effect of MPO-ANCA to this binding	499:546	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	6	5	theme	chlorination	422:433	arg1	activity					435:442	The chlorination activity	418:442	The chlorination activity of MPO	418:449	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	11	6	theme	β-galactopyranoside	1475:1493	arg1	Removal					1446:1452	Removal	1446:1452	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase	1446:1513	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001).
27643667	12	7	with	binding	1688:1694	arg1	ceruloplasmin					1701:1713	ceruloplasmin	1701:1713	ceruloplasmin	1701:1713	CONCLUSIONS: Deglycosylation decreased oxidation activity of MPO and its binding with ceruloplasmin.
27643667	7	8	gly	de-glycosylated	569:583	arg1	MPOs					585:588	Three de-glycosylated MPOs	563:588	Three de-glycosylated MPOs	563:588	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	11	9	theme	α-neuraminidase	1586:1600	arg1	removal					1575:1581	the removal	1571:1581	the removal of α-neuraminidase (P < 0.001)	1571:1612	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001).
27643667	8	10	dep	0.35 ± 0.02	870:880	arg1	P < 0.001					899:907	P < 0.001	899:907	P < 0.001	899:907	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	11	theme	most	924:927	arg1	significance					929:940	the most significance	920:940	the most significance	920:940	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	10	12	theme	core	1347:1350	arg1	removal					1262:1268	the removal	1258:1268	the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002)	1258:1443	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	3	13	theme	N-linked	208:215	arg1	sites					231:235	five N-linked glycosylation sites	203:235	five N-linked glycosylation sites	203:235	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	10	14	dep	%	1363:1363	arg1	P = 0.001					1382:1390	P = 0.001	1382:1390	P = 0.001	1382:1390	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	7	15	theme	de-glycosylated	569:583	arg1	MPOs					585:588	Three de-glycosylated MPOs	563:588	Three de-glycosylated MPOs	563:588	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	4	16	theme	pattern	286:292	arg1	effect					262:267	The effect	258:267	The effect of glycosylation pattern to the functions of MPO	258:316	The effect of glycosylation pattern to the functions of MPO is barely known.
27643667	7	17	used	used	595:598	arg2	MPOs					585:588	Three de-glycosylated MPOs	563:588	Three de-glycosylated MPOs	563:588	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	12	18	theme	oxidation	1654:1662	arg1	activity					1664:1671	oxidation activity	1654:1671	oxidation activity of MPO	1654:1678	CONCLUSIONS: Deglycosylation decreased oxidation activity of MPO and its binding with ceruloplasmin.
27643667	10	19	theme	acid	1289:1292	arg1	removal					1262:1268	the removal	1258:1268	the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002)	1258:1443	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	3	20	theme	heavy	244:248	arg1	chains					250:255	its heavy chains	240:255	its heavy chains	240:255	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	1	21	from	vasculitis	147:156	arg1	AIM					87:89	AIM	87:89	AIM: Myeloperoxidase (MPO) is pathogenic in ANCA associated vasculitis.	87:157	AIM: Myeloperoxidase (MPO) is pathogenic in ANCA associated vasculitis.
27643667	1	21	from	vasculitis	147:156	arg1	pathogenic					117:126	pathogenic	117:126	pathogenic	117:126	AIM: Myeloperoxidase (MPO) is pathogenic in ANCA associated vasculitis.
27643667	4	22	theme	glycosylation	272:284	arg1	pattern					286:292	glycosylation pattern	272:292	glycosylation pattern	272:292	The effect of glycosylation pattern to the functions of MPO is barely known.
27643667	10	23	from	deglycosylation	1227:1241	arg1	removal					1262:1268	the removal	1258:1268	the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002)	1258:1443	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	8	24	theme	sialic	857:862	arg1	0.50 ± 0.04					886:896	0.50 ± 0.04	886:896	0.50 ± 0.04	886:896	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	24	theme	sialic	857:862	arg1	0.35 ± 0.02					870:880	0.35 ± 0.02	870:880	0.35 ± 0.02	870:880	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	24	theme	sialic	857:862	arg1	acid					864:867	α-linked sialic acid	848:867	α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001)	848:908	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	10	25	dep	%	1415:1415	arg1	P = 0.002					1434:1442	P = 0.002	1434:1442	P = 0.002	1434:1442	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	13	26	theme	MPO	1779:1781	arg1	effect					1769:1774	the microbicidal effect	1752:1774	the microbicidal effect	1752:1774	Deglycosylation could also decrease the microbicidal effect of MPO, which might contribute to more severe infections and inflammation.
27643667	12	27	with	activity	1664:1671	arg1	ceruloplasmin					1701:1713	ceruloplasmin	1701:1713	ceruloplasmin	1701:1713	CONCLUSIONS: Deglycosylation decreased oxidation activity of MPO and its binding with ceruloplasmin.
27643667	8	28	theme	α-linked	848:855	arg1	0.50 ± 0.04					886:896	0.50 ± 0.04	886:896	0.50 ± 0.04	886:896	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	28	theme	α-linked	848:855	arg1	0.35 ± 0.02					870:880	0.35 ± 0.02	870:880	0.35 ± 0.02	870:880	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	28	theme	α-linked	848:855	arg1	acid					864:867	α-linked sialic acid	848:867	α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001)	848:908	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	14	29	gly	Deglycosylated	1851:1864	arg1	MPO					1866:1868	Deglycosylated MPO	1851:1868	Deglycosylated MPO	1851:1868	Deglycosylated MPO presented less antigenicity to MPO-ANCA, which indicated the contribution of glycans to MPO epitopes.
27643667	11	30	theme	α-neuraminidase	1499:1513	arg1	Removal					1446:1452	Removal	1446:1452	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase	1446:1513	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001).
27643667	10	31	gly	deglycosylation	1227:1241	arg1	removal					1262:1268	the removal	1258:1268	the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002)	1258:1443	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	32	theme	GlcNAc	1397:1402	arg1	removal					1262:1268	the removal	1258:1268	the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002)	1258:1443	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	3	33	contain	has	199:201	arg2	sites					231:235	five N-linked glycosylation sites	203:235	five N-linked glycosylation sites	203:235	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	3	33	contain	has	199:201	arg1	MPO					195:197	MPO	195:197	MPO	195:197	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	10	34	link	α-linked	1273:1280	arg1	acid					1289:1292	α-linked sialic acid	1273:1292	α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009)	1273:1333	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	34	link	α-linked	1273:1280	arg1	%					1305:1305	71.2 ± 5.1%	1295:1305	71.2 ± 5.1%	1295:1305	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	34	link	α-linked	1273:1280	arg1	%					1321:1321	88.3 ± 1.0%	1311:1321	88.3 ± 1.0%	1311:1321	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	1	35	from	pathogenic	117:126	arg1	vasculitis					147:156	ANCA associated vasculitis	131:156	ANCA associated vasculitis	131:156	AIM: Myeloperoxidase (MPO) is pathogenic in ANCA associated vasculitis.
27643667	9	36	theme	innermost	1092:1100	arg1	GlcNAc					1102:1107	innermost GlcNAc	1092:1107	innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001)	1092:1148	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	8	37	theme	intact	696:701	arg1	MPO					703:705	intact MPO	696:705	intact MPO	696:705	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	38	link	α-linked	848:855	arg1	0.50 ± 0.04					886:896	0.50 ± 0.04	886:896	0.50 ± 0.04	886:896	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	38	link	α-linked	848:855	arg1	0.35 ± 0.02					870:880	0.35 ± 0.02	870:880	0.35 ± 0.02	870:880	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	38	link	α-linked	848:855	arg1	acid					864:867	α-linked sialic acid	848:867	α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001)	848:908	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	2	39	theme	bactericidal	175:186	arg1	agent					188:192	bactericidal agent	175:192	bactericidal agent	175:192	It also acts as bactericidal agent.
27643667	9	40	theme	GlcNAc	1102:1107	arg1	removal					1081:1087	the removal	1077:1087	the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001)	1077:1148	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	3	41	link	N-linked	208:215	arg1	sites					231:235	five N-linked glycosylation sites	203:235	five N-linked glycosylation sites	203:235	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	9	42	theme	binding	971:977	arg1	capacity					979:986	the binding capacity	967:986	the binding capacity between MPO and its physiological inhibitor-ceruloplasmin	967:1044	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	10	43	theme	sialic	1282:1287	arg1	acid					1289:1292	α-linked sialic acid	1273:1292	α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009)	1273:1333	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	43	theme	sialic	1282:1287	arg1	%					1305:1305	71.2 ± 5.1%	1295:1305	71.2 ± 5.1%	1295:1305	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	43	theme	sialic	1282:1287	arg1	%					1321:1321	88.3 ± 1.0%	1311:1321	88.3 ± 1.0%	1311:1321	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	14	44	theme	MPO	1958:1960	arg1	epitopes					1962:1969	MPO epitopes	1958:1969	MPO epitopes	1958:1969	Deglycosylated MPO presented less antigenicity to MPO-ANCA, which indicated the contribution of glycans to MPO epitopes.
27643667	13	45	theme	severe	1815:1820	arg1	infections					1822:1831	more severe infections	1810:1831	more severe infections	1810:1831	Deglycosylation could also decrease the microbicidal effect of MPO, which might contribute to more severe infections and inflammation.
27643667	3	46	gly	glycosylation	217:229	arg2	five					203:206	five	203:206	five	203:206	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	3	46	gly	glycosylation	217:229	arg2	sites					231:235	five N-linked glycosylation sites	203:235	five N-linked glycosylation sites	203:235	MPO has five N-linked glycosylation sites on its heavy chains.
27643667	8	47	attach	presented	910:918	arg2	removing					771:778	removing	771:778	removing	771:778	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	47	attach	presented	910:918	arg1	which					765:769	which	765:769	which	765:769	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	0	48	theme	oxidation	31:39	arg1	activity					41:48	oxidation activity	31:48	oxidation activity	31:48	Deglycosylation influences the oxidation activity and antigenicity of myeloperoxidase.
27643667	14	49	theme	Deglycosylated	1851:1864	arg1	MPO					1866:1868	Deglycosylated MPO	1851:1868	Deglycosylated MPO	1851:1868	Deglycosylated MPO presented less antigenicity to MPO-ANCA, which indicated the contribution of glycans to MPO epitopes.
27643667	7	50	from	influence	613:621	arg1	effect					658:663	microbicidal effect	645:663	microbicidal effect of MPO	645:670	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	7	51	theme	MPO	668:670	arg1	effect					658:663	microbicidal effect	645:663	microbicidal effect of MPO	645:670	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	14	52	theme	glycans	1947:1953	arg1	contribution					1931:1942	the contribution	1927:1942	the contribution of glycans to MPO epitopes	1927:1969	Deglycosylated MPO presented less antigenicity to MPO-ANCA, which indicated the contribution of glycans to MPO epitopes.
27643667	11	53	theme	MPO	1555:1557	arg1	effect					1545:1550	the bactericidal effect	1528:1550	the bactericidal effect of MPO	1528:1557	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001).
27643667	13	54	theme	microbicidal	1756:1767	arg1	effect					1769:1774	the microbicidal effect	1752:1774	the microbicidal effect	1752:1774	Deglycosylation could also decrease the microbicidal effect of MPO, which might contribute to more severe infections and inflammation.
27643667	7	55	theme	microbicidal	645:656	arg1	effect					658:663	microbicidal effect	645:663	microbicidal effect of MPO	645:670	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	0	56	dep	activity	41:48	arg1	the					27:29	the	27:29	the	27:29	Deglycosylation influences the oxidation activity and antigenicity of myeloperoxidase.
27643667	11	57	theme	bactericidal	1532:1543	arg1	effect					1545:1550	the bactericidal effect	1528:1550	the bactericidal effect of MPO	1528:1557	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001).
27643667	12	58	theme	MPO	1676:1678	arg1	binding					1688:1694	its binding	1684:1694	its binding with ceruloplasmin	1684:1713	CONCLUSIONS: Deglycosylation decreased oxidation activity of MPO and its binding with ceruloplasmin.
27643667	12	58	theme	MPO	1676:1678	arg1	activity					1664:1671	oxidation activity	1654:1671	oxidation activity of MPO	1654:1678	CONCLUSIONS: Deglycosylation decreased oxidation activity of MPO and its binding with ceruloplasmin.
27643667	8	59	theme	chlorination	708:719	arg1	activity					721:728	chlorination activity	708:728	chlorination activity of deglycosylated MPO	708:750	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	6	60	theme	MPO	447:449	arg1	effect					513:518	the reversing effect	499:518	the reversing effect of MPO-ANCA to this binding	499:546	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	6	60	theme	MPO	447:449	arg1	binding					456:462	the binding	452:462	the binding between ceruloplasmin and MPO	452:492	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	6	60	theme	MPO	447:449	arg1	activity					435:442	The chlorination activity	418:442	The chlorination activity of MPO	418:449	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	11	61	theme	GlcNAc	1467:1472	arg1	Removal					1446:1452	Removal	1446:1452	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase	1446:1513	Removal of innermost GlcNAc, β-galactopyranoside and α-neuraminidase could weaken the bactericidal effect of MPO, especially the removal of α-neuraminidase (P < 0.001).
27643667	8	62	gly	deglycosylated	733:746	arg1	MPO					748:750	deglycosylated MPO	733:750	deglycosylated MPO	733:750	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	63	theme	deglycosylated	733:746	arg1	MPO					748:750	deglycosylated MPO	733:750	deglycosylated MPO	733:750	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	10	64	dep	%	1305:1305	arg1	P = 0.009					1324:1332	P = 0.009	1324:1332	P = 0.009	1324:1332	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	7	65	theme	deglycosylation	626:640	arg1	influence					613:621	the influence	609:621	the influence of deglycosylation on microbicidal effect of MPO	609:670	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	9	66	dep	GlcNAc	1102:1107	arg1	0.37 ± 0.04					1110:1120	0.37 ± 0.04	1110:1120	0.37 ± 0.04	1110:1120	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	9	66	dep	GlcNAc	1102:1107	arg1	P < 0.001					1139:1147	P < 0.001	1139:1147	P < 0.001	1139:1147	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	1	67	theme	ANCA	131:134	arg1	vasculitis					147:156	ANCA associated vasculitis	131:156	ANCA associated vasculitis	131:156	AIM: Myeloperoxidase (MPO) is pathogenic in ANCA associated vasculitis.
27643667	9	68	theme	physiological	1008:1020	arg1	inhibitor-ceruloplasmin					1022:1044	its physiological inhibitor-ceruloplasmin	1004:1044	its physiological inhibitor-ceruloplasmin	1004:1044	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	10	69	theme	α-linked	1273:1280	arg1	acid					1289:1292	α-linked sialic acid	1273:1292	α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009)	1273:1333	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	69	theme	α-linked	1273:1280	arg1	%					1305:1305	71.2 ± 5.1%	1295:1305	71.2 ± 5.1%	1295:1305	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	69	theme	α-linked	1273:1280	arg1	%					1321:1321	88.3 ± 1.0%	1311:1321	88.3 ± 1.0%	1311:1321	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	6	70	theme	MPO-ANCA	523:530	arg1	effect					513:518	the reversing effect	499:518	the reversing effect of MPO-ANCA to this binding	499:546	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	6	70	theme	MPO-ANCA	523:530	arg1	binding					456:462	the binding	452:462	the binding between ceruloplasmin and MPO	452:492	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	6	70	theme	MPO-ANCA	523:530	arg1	activity					435:442	The chlorination activity	418:442	The chlorination activity of MPO	418:449	The chlorination activity of MPO, the binding between ceruloplasmin and MPO, and the reversing effect of MPO-ANCA to this binding were measured.
27643667	9	71	theme	most	1056:1059	arg1	significance					1061:1072	the most significance	1052:1072	the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001)	1052:1148	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	9	72	from	significance	1061:1072	arg1	removal					1081:1087	the removal	1077:1087	the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001)	1077:1148	Deglycosylation reduced the binding capacity between MPO and its physiological inhibitor-ceruloplasmin, with the most significance on the removal of innermost GlcNAc (0.37 ± 0.04 vs. 1.06 ± 0.11, P < 0.001).
27643667	10	73	theme	chitobiose	1336:1345	arg1	%					1363:1363	73.6 ± 1.9%	1353:1363	73.6 ± 1.9%	1353:1363	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	73	theme	chitobiose	1336:1345	arg1	%					1379:1379	88.3 ± 1.0%	1369:1379	88.3 ± 1.0%	1369:1379	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	10	73	theme	chitobiose	1336:1345	arg1	core					1347:1350	chitobiose core	1336:1350	chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001)	1336:1391	Binding between MPO and ceruloplasmin was hardly reversed by MPO-ANCA after deglycosylation, especially on the removal of α-linked sialic acid (71.2 ± 5.1% vs. 88.3 ± 1.0%, P = 0.009), chitobiose core (73.6 ± 1.9% vs. 88.3 ± 1.0%, P = 0.001) and GlcNAc (77.9 ± 1.9% vs. 88.3 ± 1.0%, P = 0.002).
27643667	1	74	theme	associated	136:145	arg1	vasculitis					147:156	ANCA associated vasculitis	131:156	ANCA associated vasculitis	131:156	AIM: Myeloperoxidase (MPO) is pathogenic in ANCA associated vasculitis.
27643667	7	75	gly	deglycosylation	626:640	arg1	microbicidal					645:656	microbicidal effect	645:663	microbicidal effect of MPO	645:670	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	7	75	gly	deglycosylation	626:640	arg1	MPO					668:670	MPO	668:670	MPO	668:670	Three de-glycosylated MPOs were used to assay the influence of deglycosylation on microbicidal effect of MPO.
27643667	0	76	theme	myeloperoxidase	70:84	arg1	antigenicity					54:65	antigenicity	54:65	antigenicity	54:65	Deglycosylation influences the oxidation activity and antigenicity of myeloperoxidase.
27643667	0	76	theme	myeloperoxidase	70:84	arg1	activity					41:48	oxidation activity	31:48	oxidation activity	31:48	Deglycosylation influences the oxidation activity and antigenicity of myeloperoxidase.
27643667	8	77	theme	MPO	748:750	arg1	activity					721:728	chlorination activity	708:728	chlorination activity of deglycosylated MPO	708:750	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	78	dep	β-galactopyranoside	783:801	arg1	0.50 ± 0.04					820:830	0.50 ± 0.04	820:830	0.50 ± 0.04	820:830	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	8	78	dep	β-galactopyranoside	783:801	arg1	0.35 ± 0.02					804:814	0.35 ± 0.02	804:814	0.35 ± 0.02	804:814	RESULTS: Compared with intact MPO, chlorination activity of deglycosylated MPO declined, in which removing of β-galactopyranoside (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) and α-linked sialic acid (0.35 ± 0.02 vs. 0.50 ± 0.04, P < 0.001) presented the most significance.
27643667	5	79	theme	different	381:389	arg1	glycans					391:397	different glycans	381:397	different glycans	381:397	METHODS: We used eight glycosidases to remove different glycans on MPO separately.
28497210	1	0	from	endemic	194:200	arg1	parts					210:214	many parts	205:214	many parts of the country	205:229	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	7	1	from	variations	984:993	arg1	HA					998:999	HA	998:999	HA	998:999	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	7	1	from	variations	984:993	arg1	gene					1008:1011	NA gene	1005:1011	NA gene	1005:1011	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	8	2	with	position	1169:1176	arg1	strain					1191:1196	vaccine strain A/California/07/2009	1183:1217	vaccine strain A/California/07/2009	1183:1217	Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually.
28497210	7	3	theme	N-linked	1040:1047	arg1	motif					1063:1067	the N-linked glycosylation motif	1036:1067	the N-linked glycosylation motif which may lead to immune evasion	1036:1100	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	9	4	theme	continuous	1371:1380	arg1	surveillance					1382:1393	continuous surveillance	1371:1393	continuous surveillance	1371:1393	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	6	5	theme	HA	817:818	arg1	gene					820:823	the HA gene	813:823	the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain	813:895	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	2	6	theme	Influenza	232:240	arg1	viruses					244:250	Influenza A viruses	232:250	Influenza A viruses	232:250	Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations.
28497210	4	7	theme	cell	589:592	arg1	line					594:597	Madin-Darby canine kidney cell line	563:597	Madin-Darby canine kidney cell line for virus isolation	563:617	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	8	8	theme	Phylogenetic	1103:1114	arg1	analysis					1116:1123	Phylogenetic analysis	1103:1123	Phylogenetic analysis of the isolates	1103:1139	Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually.
28497210	6	9	theme	acid	795:798	arg1	sequences					800:808	Nucleotide and amino acid sequences	774:808	sequences	800:808	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	9	10	theme	present	1276:1282	arg1	study					1284:1288	the present study	1272:1288	the present study	1272:1288	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	8	11	theme	vaccine	1183:1189	arg1	strain					1191:1196	vaccine strain A/California/07/2009	1183:1217	vaccine strain A/California/07/2009	1183:1217	Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually.
28497210	5	12	theme	phylogenetic	634:645	arg1	analysis					647:654	Molecular and phylogenetic analysis	620:654	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates	620:692	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	1	13	located	detected	138:145	arg2	virus					122:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	1	13	located	detected	138:145	arg1	India					150:154	India	150:154	India in May 2009 which subsequently became endemic in many parts of the country	150:229	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	8	14	theme	isolates	1132:1139	arg1	analysis					1116:1123	Phylogenetic analysis	1103:1123	Phylogenetic analysis of the isolates	1103:1139	Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually.
28497210	6	15	theme	A/California/07/2009-vaccine	861:888	arg1	strain					890:895	A/California/07/2009-vaccine strain	861:895	A/California/07/2009-vaccine strain	861:895	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	4	16	theme	canine	575:580	arg1	line					594:597	Madin-Darby canine kidney cell line	563:597	Madin-Darby canine kidney cell line for virus isolation	563:617	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	1	17	from	parts	210:214	arg1	endemic					194:200	endemic	194:200	endemic	194:200	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	5	18	theme	strains	765:771	arg1	evolution					726:734	evolution	726:734	evolution	726:734	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	5	18	theme	strains	765:771	arg1	diversity					748:756	genetic diversity	740:756	genetic diversity	740:756	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	7	19	theme	acid	979:982	arg1	variations					984:993	Amino acid variations	973:993	Amino acid variations in HA and NA gene	973:1011	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	1	20	theme	A	108:108	arg1	virus					122:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	6	21	theme	isolates	835:842	arg1	gene					820:823	the HA gene	813:823	the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain	813:895	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	5	22	theme	Molecular	620:628	arg1	analysis					647:654	Molecular and phylogenetic analysis	620:654	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates	620:692	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	1	23	theme	H1N1	111:114	arg1	virus					122:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	5	24	theme	pdm	678:680	arg1	isolates					685:692	influenza A (H1N1) pdm 09 isolates	659:692	influenza A (H1N1) pdm 09 isolates	659:692	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	6	25	theme	located	941:947	arg1	differences					929:939	14 specific amino acid differences	906:939	14 specific amino acid differences located at the antigenic sites	906:970	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	0	26	theme	Virus	61:65	arg1	Isolates					67:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates	28:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai	28:86	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	6	27	theme	acid	924:927	arg1	differences					929:939	14 specific amino acid differences	906:939	14 specific amino acid differences located at the antigenic sites	906:970	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	5	28	theme	A	669:669	arg1	isolates					685:692	influenza A (H1N1) pdm 09 isolates	659:692	influenza A (H1N1) pdm 09 isolates	659:692	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	6	29	theme	specific	909:916	arg1	differences					929:939	14 specific amino acid differences	906:939	14 specific amino acid differences located at the antigenic sites	906:970	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	3	30	theme	A	384:384	arg1	viruses					400:406	influenza A (H1N1) pdm 09 viruses	374:406	influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period	374:473	The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period.
28497210	2	31	theme	antigenic	321:329	arg1	variations					331:340	antigenic variations	321:340	antigenic variations	321:340	Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations.
28497210	0	32	theme	Genetic	0:6	arg1	Characterization					8:23	Genetic Characterization	0:23	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.	0:87	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	1	33	theme	country	223:229	arg1	parts					210:214	many parts	205:214	many parts of the country	205:229	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	3	34	theme	pdm	393:395	arg1	viruses					400:406	influenza A (H1N1) pdm 09 viruses	374:406	influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period	374:473	The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period.
28497210	5	35	theme	genetic	740:746	arg1	diversity					748:756	genetic diversity	740:756	genetic diversity	740:756	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	6	36	theme	amino	789:793	arg1	sequences					800:808	Nucleotide and amino acid sequences	774:808	sequences	800:808	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	1	37	theme	Pandemic	89:96	arg1	virus					122:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	0	38	theme	A	38:38	arg1	Isolates					67:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates	28:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai	28:86	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	6	39	theme	Nucleotide	774:783	arg1	sequences					800:808	Nucleotide and amino acid sequences	774:808	sequences	800:808	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	0	40	theme	Pandemic	47:54	arg1	Isolates					67:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates	28:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai	28:86	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	2	41	theme	immune	282:287	arg1	response					289:296	the immune response	278:296	the immune response	278:296	Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations.
28497210	9	42	theme	influenza	1321:1329	arg1	viruses					1331:1337	influenza viruses	1321:1337	influenza viruses	1321:1337	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	4	43	theme	pdm	529:531	arg1	viruses					536:542	influenza A (H1N1) pdm 09 viruses	510:542	influenza A (H1N1) pdm 09 viruses	510:542	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	3	44	theme	pandemic	441:448	arg1	period					468:473	the pandemic and post-pandemic period	437:473	the pandemic and post-pandemic period	437:473	The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period.
28497210	4	45	theme	kidney	582:587	arg1	line					594:597	Madin-Darby canine kidney cell line	563:597	Madin-Darby canine kidney cell line for virus isolation	563:617	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	6	46	theme	Mumbai	828:833	arg1	isolates					835:842	Mumbai isolates	828:842	Mumbai isolates when compared to A/California/07/2009-vaccine strain	828:895	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	5	47	theme	09	682:683	arg1	isolates					685:692	influenza A (H1N1) pdm 09 isolates	659:692	influenza A (H1N1) pdm 09 isolates	659:692	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	1	48	theme	many	205:208	arg1	parts					210:214	many parts	205:214	many parts of the country	205:229	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	6	49	theme	gene	820:823	arg1	sequences					800:808	Nucleotide and amino acid sequences	774:808	sequences	800:808	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	4	50	theme	A	520:520	arg1	viruses					536:542	influenza A (H1N1) pdm 09 viruses	510:542	influenza A (H1N1) pdm 09 viruses	510:542	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	2	51	theme	A	242:242	arg1	viruses					244:250	Influenza A viruses	232:250	Influenza A viruses	232:250	Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations.
28497210	9	52	theme	surveillance	1382:1393	arg1	importance					1357:1366	the importance	1353:1366	the importance of continuous surveillance during influenza outbreaks	1353:1420	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	5	53	dep	evolution	726:734	arg1	the					722:724	the	722:724	the	722:724	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	3	54	theme	post-pandemic	454:466	arg1	period					468:473	the pandemic and post-pandemic period	437:473	the pandemic and post-pandemic period	437:473	The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period.
28497210	9	55	theme	influenza	1402:1410	arg1	outbreaks					1412:1420	influenza outbreaks	1402:1420	influenza outbreaks	1402:1420	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	8	56	theme	evolutionary	1156:1167	arg1	position					1169:1176	their evolutionary position	1150:1176	their evolutionary position with vaccine strain A/California/07/2009	1150:1217	Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually.
28497210	5	57	theme	isolates	685:692	arg1	analysis					647:654	Molecular and phylogenetic analysis	620:654	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates	620:692	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	7	58	theme	NA	1005:1006	arg1	gene					1008:1011	NA gene	1005:1011	NA gene	1005:1011	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	6	59	from	sites	966:970	arg1	located					941:947	located	941:947	located	941:947	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	9	60	from	findings	1260:1267	arg1	study					1284:1288	the present study	1272:1288	the present study	1272:1288	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	4	61	theme	Madin-Darby	563:573	arg1	line					594:597	Madin-Darby canine kidney cell line	563:597	Madin-Darby canine kidney cell line for virus isolation	563:617	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	7	62	theme	Amino	973:977	arg1	variations					984:993	Amino acid variations	973:993	Amino acid variations in HA and NA gene	973:1011	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	1	63	theme	influenza	98:106	arg1	virus					122:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus	89:126	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	6	64	theme	antigenic	956:964	arg1	sites					966:970	the antigenic sites	952:970	the antigenic sites	952:970	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	0	65	from	Mumbai	81:86	arg1	Isolates					67:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates	28:74	Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai	28:86	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	0	65	from	Mumbai	81:86	arg1	Characterization					8:23	Genetic Characterization	0:23	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.	0:87	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	1	66	from	India	150:154	arg1	May					159:161	May 2009	159:166	May 2009	159:166	Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country.
28497210	4	67	theme	virus	603:607	arg1	isolation					609:617	virus isolation	603:617	virus isolation	603:617	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	0	68	theme	Isolates	67:74	arg1	Characterization					8:23	Genetic Characterization	0:23	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.	0:87	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	0	69	from	Characterization	8:23	arg1	Mumbai					81:86	Mumbai	81:86	Mumbai	81:86	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	5	70	theme	influenza	659:667	arg1	H1N1					672:675	H1N1	672:675	H1N1	672:675	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	5	70	theme	influenza	659:667	arg1	A					669:669	influenza A	659:669	influenza A (H1N1) pdm 09 isolates	659:692	Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains.
28497210	6	71	theme	amino	918:922	arg1	differences					929:939	14 specific amino acid differences	906:939	14 specific amino acid differences located at the antigenic sites	906:970	Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites.
28497210	2	72	theme	variations	331:340	arg1	ability					310:316	its ability	306:316	its ability of antigenic variations	306:340	Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations.
28497210	7	73	theme	immune	1087:1092	arg1	evasion					1094:1100	immune evasion	1087:1100	immune evasion	1087:1100	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	4	74	theme	positive	497:504	arg1	swabs					491:495	Nasopharyngeal swabs	476:495	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses	476:542	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	3	75	theme	influenza	374:382	arg1	A					384:384	influenza A	374:384	influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period	374:473	The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period.
28497210	3	75	theme	influenza	374:382	arg1	H1N1					387:390	H1N1	387:390	H1N1	387:390	The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period.
28497210	0	76	theme	Influenza	28:36	arg1	H1N1					41:44	H1N1	41:44	H1N1	41:44	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	0	76	theme	Influenza	28:36	arg1	A					38:38	Influenza A	28:38	Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai	28:86	Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.
28497210	4	77	theme	influenza	510:518	arg1	H1N1					523:526	H1N1	523:526	H1N1	523:526	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	4	77	theme	influenza	510:518	arg1	A					520:520	influenza A	510:520	influenza A (H1N1) pdm 09 viruses	510:542	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	3	78	theme	09	397:398	arg1	viruses					400:406	influenza A (H1N1) pdm 09 viruses	374:406	influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period	374:473	The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period.
28497210	9	79	theme	genetic	1298:1304	arg1	variability					1306:1316	genetic variability	1298:1316	genetic variability of influenza viruses	1298:1337	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	7	80	from	changes	1025:1031	arg1	motif					1063:1067	the N-linked glycosylation motif	1036:1067	the N-linked glycosylation motif which may lead to immune evasion	1036:1100	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	7	81	link	N-linked	1040:1047	arg1	motif					1063:1067	the N-linked glycosylation motif	1036:1067	the N-linked glycosylation motif which may lead to immune evasion	1036:1100	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	7	82	theme	glycosylation	1049:1061	arg1	motif					1063:1067	the N-linked glycosylation motif	1036:1067	the N-linked glycosylation motif which may lead to immune evasion	1036:1100	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	2	83	contain	have	252:255	arg2	ability					261:267	the ability to evade the immune response through its ability of antigenic variations	257:340	the ability to evade the immune response through its ability of antigenic variations	257:340	Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations.
28497210	2	83	contain	have	252:255	arg1	viruses					244:250	Influenza A viruses	232:250	Influenza A viruses	232:250	Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations.
28497210	4	84	theme	Nasopharyngeal	476:489	arg1	swabs					491:495	Nasopharyngeal swabs	476:495	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses	476:542	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
28497210	7	85	gly	glycosylation	1049:1061	arg2	motif					1063:1067	the N-linked glycosylation motif	1036:1067	the N-linked glycosylation motif which may lead to immune evasion	1036:1100	Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion.
28497210	9	86	theme	viruses	1331:1337	arg1	variability					1306:1316	genetic variability	1298:1316	genetic variability of influenza viruses	1298:1337	The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.
28497210	4	87	theme	09	533:534	arg1	viruses					536:542	influenza A (H1N1) pdm 09 viruses	510:542	influenza A (H1N1) pdm 09 viruses	510:542	Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation.
29463718	2	0	from	Mutations	186:194	arg1	hTRPM4					212:217	hTRPM4	212:217	hTRPM4	212:217	Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block.
29463718	2	0	from	Mutations	186:194	arg1	TRPM4					205:209	human TRPM4	199:209	human TRPM4 (hTRPM4)	199:218	Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block.
29463718	8	1	theme	potential	1044:1052	arg1	mechanisms					1054:1063	potential mechanisms	1044:1063	potential mechanisms of regulation and gating of human full-length TRPM4	1044:1115	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	5	2	theme	selectivity	577:587	arg1	filter					589:594	the selectivity filter	573:594	the selectivity filter	573:594	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	7	3	theme	extracellular	893:905	arg1	site					907:910	an N-linked extracellular site	881:910	an N-linked extracellular site	881:910	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	5	4	theme	lower	602:606	arg1	gate					608:611	a lower gate	600:611	a lower gate at the entrance to the cytoplasmic coiled-coil domain	600:665	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	3	5	from	hTRPM4	321:326	arg1	state					356:360	a closed, Na+-bound, apo state	331:360	state	356:360	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	3	5	from	hTRPM4	321:326	arg1	pH					365:366	pH 7.5	365:370	pH 7.5	365:370	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	6	6	theme	N-terminal	747:756	arg1	domain					758:763	N-terminal domain	747:763	N-terminal domain	747:763	Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini.
29463718	5	7	theme	coiled-coil	648:658	arg1	domain					660:665	the cytoplasmic coiled-coil domain	632:665	the cytoplasmic coiled-coil domain	632:665	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	3	8	dep	state	356:360	arg1	apo					352:354	a closed, Na+-bound, apo state	331:360	apo	352:354	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	1	9	theme	potential	57:65	arg1	member					88:93	Transient receptor potential melastatin subfamily member 4	38:95	Transient receptor potential melastatin subfamily member 4 (TRPM4)	38:103	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	9	theme	potential	57:65	arg1	TRPM4					98:102	TRPM4	98:102	TRPM4	98:102	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	9	theme	potential	57:65	arg1	channel					177:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	5	10	from	entrance	620:627	arg1	gate					565:568	an upper gate	556:568	an upper gate in the selectivity filter	556:594	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	5	10	from	entrance	620:627	arg1	gate					608:611	a lower gate	600:611	a lower gate at the entrance to the cytoplasmic coiled-coil domain	600:665	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	4	11	theme	sodium	431:436	arg1	ions					438:441	Five partially hydrated sodium ions	407:441	Five partially hydrated sodium ions	407:441	Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain.
29463718	1	12	theme	melastatin	67:76	arg1	member					88:93	Transient receptor potential melastatin subfamily member 4	38:95	Transient receptor potential melastatin subfamily member 4 (TRPM4)	38:103	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	12	theme	melastatin	67:76	arg1	TRPM4					98:102	TRPM4	98:102	TRPM4	98:102	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	12	theme	melastatin	67:76	arg1	channel					177:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	13	dep	distributed	117:127	arg1	calcium-activated					130:146	calcium-activated	130:146	calcium-activated	130:146	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	13	dep	distributed	117:127	arg1	monovalent-selective					149:168	monovalent-selective	149:168	monovalent-selective	149:168	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	4	14	theme	coiled-coil	524:534	arg1	domain					536:541	the coiled-coil domain	520:541	the coiled-coil domain	520:541	Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain.
29463718	4	15	theme	hydrated	422:429	arg1	ions					438:441	Five partially hydrated sodium ions	407:441	Five partially hydrated sodium ions	407:441	Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain.
29463718	5	16	theme	upper	559:563	arg1	gate					565:568	an upper gate	556:568	an upper gate in the selectivity filter	556:594	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	6	17	theme	S4-S5	733:737	arg1	linker					739:744	the S4-S5 linker	729:744	the S4-S5 linker	729:744	Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini.
29463718	1	18	theme	subfamily	78:86	arg1	member					88:93	Transient receptor potential melastatin subfamily member 4	38:95	Transient receptor potential melastatin subfamily member 4 (TRPM4)	38:103	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	18	theme	subfamily	78:86	arg1	TRPM4					98:102	TRPM4	98:102	TRPM4	98:102	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	18	theme	subfamily	78:86	arg1	channel					177:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	7	19	from	site	907:910	arg1	sites					962:966	24 lipid binding sites	945:966	24 lipid binding sites	945:966	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	7	19	from	site	907:910	arg1	interactions					817:828	aromatic interactions	808:828	aromatic interactions via π-π bonds and cation-π bonds	808:861	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	7	19	from	site	907:910	arg1	bond					935:938	a pore-loop disulfide bond	913:938	a pore-loop disulfide bond	913:938	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	7	19	from	site	907:910	arg1	glycosylation					864:876	glycosylation	864:876	glycosylation at an N-linked extracellular site	864:910	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	1	20	theme	cation	170:175	arg1	member					88:93	Transient receptor potential melastatin subfamily member 4	38:95	Transient receptor potential melastatin subfamily member 4 (TRPM4)	38:103	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	20	theme	cation	170:175	arg1	channel					177:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	3	21	theme	closed	333:338	arg1	state					356:360	a closed, Na+-bound, apo state	331:360	state	356:360	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	3	22	from	state	356:360	arg1	structure					308:316	the electron cryomicroscopy structure	280:316	the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å	280:404	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	7	23	theme	cation-π	848:855	arg1	bonds					857:861	cation-π bonds	848:861	cation-π bonds	848:861	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	7	24	theme	lipid	948:952	arg1	sites					962:966	24 lipid binding sites	945:966	24 lipid binding sites	945:966	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	3	25	dep	closed	333:338	arg1	Na+-bound					341:349	Na+-bound	341:349	Na+-bound	341:349	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	3	26	theme	overall	378:384	arg1	resolution					386:395	an overall resolution	375:395	an overall resolution of 3.7 Å	375:404	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	8	27	theme	gating	1083:1088	arg1	mechanisms					1054:1063	potential mechanisms	1044:1063	potential mechanisms of regulation and gating of human full-length TRPM4	1044:1115	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	7	28	link	N-linked	884:891	arg1	site					907:910	an N-linked extracellular site	881:910	an N-linked extracellular site	881:910	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	0	29	theme	human	25:29	arg1	TRPM4					31:35	full-length human TRPM4	13:35	full-length human TRPM4	13:35	Structure of full-length human TRPM4.
29463718	1	30	theme	Transient	38:46	arg1	member					88:93	Transient receptor potential melastatin subfamily member 4	38:95	Transient receptor potential melastatin subfamily member 4 (TRPM4)	38:103	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	30	theme	Transient	38:46	arg1	TRPM4					98:102	TRPM4	98:102	TRPM4	98:102	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	30	theme	Transient	38:46	arg1	channel					177:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	6	31	theme	TRP	714:716	arg1	domain					718:723	the TRP domain	710:723	the TRP domain	710:723	Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini.
29463718	0	32	theme	full-length	13:23	arg1	TRPM4					31:35	full-length human TRPM4	13:35	full-length human TRPM4	13:35	Structure of full-length human TRPM4.
29463718	6	33	dep	N	770:770	arg1	termini					778:784	termini	778:784	termini	778:784	Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini.
29463718	5	34	from	gate	565:568	arg1	filter					589:594	the selectivity filter	573:594	the selectivity filter	573:594	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	7	35	theme	binding	954:960	arg1	sites					962:966	24 lipid binding sites	945:966	24 lipid binding sites	945:966	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	8	36	theme	human	1093:1097	arg1	TRPM4					1111:1115	human full-length TRPM4	1093:1115	human full-length TRPM4	1093:1115	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	3	37	theme	Å	404:404	arg1	resolution					386:395	an overall resolution	375:395	an overall resolution of 3.7 Å	375:404	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	0	38	theme	TRPM4	31:35	arg1	Structure					0:8	Structure	0:8	Structure of full-length human TRPM4	0:35	Structure of full-length human TRPM4.
29463718	5	39	theme	cytoplasmic	636:646	arg1	domain					660:665	the cytoplasmic coiled-coil domain	632:665	the cytoplasmic coiled-coil domain	632:665	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
29463718	8	40	theme	full-length	1099:1109	arg1	TRPM4					1111:1115	human full-length TRPM4	1093:1115	human full-length TRPM4	1093:1115	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	7	41	theme	disulfide	925:933	arg1	bond					935:938	a pore-loop disulfide bond	913:938	a pore-loop disulfide bond	913:938	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	8	42	theme	regulation	1068:1077	arg1	mechanisms					1054:1063	potential mechanisms	1044:1063	potential mechanisms of regulation and gating of human full-length TRPM4	1044:1115	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	3	43	theme	electron	284:291	arg1	structure					308:316	the electron cryomicroscopy structure	280:316	the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å	280:404	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	4	44	theme	pore	495:498	arg1	center					470:475	the center	466:475	the center of the conduction pore	466:498	Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain.
29463718	4	44	theme	pore	495:498	arg1	entrance					508:515	the entrance	504:515	the entrance to the coiled-coil domain	504:541	Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain.
29463718	4	45	theme	conduction	484:493	arg1	pore					495:498	the conduction pore	480:498	the conduction pore	480:498	Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain.
29463718	3	46	theme	cryomicroscopy	293:306	arg1	structure					308:316	the electron cryomicroscopy structure	280:316	the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å	280:404	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	3	47	from	structure	308:316	arg1	state					356:360	a closed, Na+-bound, apo state	331:360	state	356:360	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	1	48	theme	receptor	48:55	arg1	member					88:93	Transient receptor potential melastatin subfamily member 4	38:95	Transient receptor potential melastatin subfamily member 4 (TRPM4)	38:103	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	48	theme	receptor	48:55	arg1	TRPM4					98:102	TRPM4	98:102	TRPM4	98:102	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	48	theme	receptor	48:55	arg1	channel					177:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	8	49	theme	TRP	1019:1021	arg1	channels					1023:1030	other TRP channels	1013:1030	other TRP channels	1013:1030	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	7	50	theme	pore-loop	915:923	arg1	bond					935:938	a pore-loop disulfide bond	913:938	a pore-loop disulfide bond	913:938	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	7	51	theme	π-π	834:836	arg1	bonds					838:842	π-π bonds	834:842	π-π bonds	834:842	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	8	52	theme	other	1013:1017	arg1	channels					1023:1030	other TRP channels	1013:1030	other TRP channels	1013:1030	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	2	53	theme	human	199:203	arg1	hTRPM4					212:217	hTRPM4	212:217	hTRPM4	212:217	Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block.
29463718	2	53	theme	human	199:203	arg1	TRPM4					205:209	human TRPM4	199:209	human TRPM4 (hTRPM4)	199:218	Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block.
29463718	2	54	theme	heart	251:255	arg1	block					257:261	progressive familial heart block	230:261	progressive familial heart block	230:261	Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block.
29463718	6	55	theme	Intramolecular	668:681	arg1	interactions					683:694	Intramolecular interactions	668:694	Intramolecular interactions	668:694	Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini.
29463718	1	56	theme	distributed	117:127	arg1	member					88:93	Transient receptor potential melastatin subfamily member 4	38:95	Transient receptor potential melastatin subfamily member 4 (TRPM4)	38:103	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	1	56	theme	distributed	117:127	arg1	channel					177:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	a widely distributed, calcium-activated, monovalent-selective cation channel	108:183	Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel.
29463718	7	57	theme	aromatic	808:815	arg1	interactions					817:828	aromatic interactions	808:828	aromatic interactions via π-π bonds and cation-π bonds	808:861	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	8	58	theme	TRPM4	1111:1115	arg1	gating					1083:1088	gating	1083:1088	gating	1083:1088	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	8	58	theme	TRPM4	1111:1115	arg1	regulation					1068:1077	regulation	1068:1077	regulation	1068:1077	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	3	59	theme	hTRPM4	321:326	arg1	structure					308:316	the electron cryomicroscopy structure	280:316	the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å	280:404	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	2	60	theme	familial	242:249	arg1	block					257:261	progressive familial heart block	230:261	progressive familial heart block	230:261	Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block.
29463718	8	61	with	contrast	984:991	arg1	channels					1023:1030	other TRP channels	1013:1030	other TRP channels	1013:1030	We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.
29463718	7	62	gly	glycosylation	864:876	arg1	site					907:910	an N-linked extracellular site	881:910	an N-linked extracellular site	881:910	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	7	62	gly	glycosylation	864:876	arg2	site					907:910	an N-linked extracellular site	881:910	an N-linked extracellular site	881:910	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	3	63	from	pH	365:366	arg1	hTRPM4					321:326	hTRPM4	321:326	hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å	321:404	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	3	63	from	pH	365:366	arg1	state					356:360	a closed, Na+-bound, apo state	331:360	state	356:360	Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å.
29463718	2	64	theme	progressive	230:240	arg1	block					257:261	progressive familial heart block	230:261	progressive familial heart block	230:261	Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block.
29463718	7	65	theme	N-linked	884:891	arg1	site					907:910	an N-linked extracellular site	881:910	an N-linked extracellular site	881:910	Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites.
29463718	5	66	from	gate	608:611	arg1	filter					589:594	the selectivity filter	573:594	the selectivity filter	573:594	We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain.
30086619	0	0	theme	Asn-X-Ser/Thr	94:106	arg1	motif					108:112	an important Asn-X-Ser/Thr motif	81:112	an important Asn-X-Ser/Thr motif for its activity	81:129	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	1	1	theme	enzymes	163:169	arg1	Hyaluronidases					132:145	Hyaluronidases	132:145	Hyaluronidases	132:145	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	1	1	theme	enzymes	163:169	arg1	family					153:158	a family	151:158	a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex	151:290	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	1	2	theme	extracellular	244:256	arg1	matrix					258:263	the extracellular matrix	240:263	the extracellular matrix	240:263	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	2	3	theme	reading	464:470	arg1	frame					472:476	the bovine SPAM1 open reading frame	442:476	the bovine SPAM1 open reading frame	442:476	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	3	4	theme	gel	681:683	arg1	electrophoresis					685:699	gel electrophoresis	681:699	gel electrophoresis	681:699	Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.
30086619	6	5	theme	activity	1156:1163	arg1	inhibition					1131:1140	significant inhibition	1119:1140	significant inhibition of hyaluronic activity	1119:1163	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	7	6	theme	bovine	1178:1183	arg1	SPAM1					1185:1189	Recombinant bovine SPAM1	1166:1189	Recombinant bovine SPAM1	1166:1189	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	7	7	contain	has	1191:1193	arg2	ability					1256:1262	hyaluronan degradation and cumulus oocyte complex dispersion ability	1195:1262	ability	1256:1262	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	7	7	contain	has	1191:1193	arg1	SPAM1					1185:1189	Recombinant bovine SPAM1	1166:1189	Recombinant bovine SPAM1	1166:1189	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	7	7	contain	has	1191:1193	arg2	degradation					1206:1216	hyaluronan degradation and cumulus oocyte complex dispersion ability	1195:1262	degradation	1206:1216	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	2	8	theme	expression	508:517	arg1	vector					519:524	the mammalian expression vector	494:524	the mammalian expression vector pCXN2	494:530	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	7	9	theme	Recombinant	1166:1176	arg1	SPAM1					1185:1189	Recombinant bovine SPAM1	1166:1189	Recombinant bovine SPAM1	1166:1189	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	0	10	theme	motif	108:112	arg1	Characterization					0:15	Characterization	0:15	Characterization of recombinant bovine sperm hyaluronidase	0:57	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	0	10	theme	motif	108:112	arg1	identification					63:76	identification	63:76	identification of an important Asn-X-Ser/Thr motif for its activity	63:129	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	2	11	theme	cell	567:570	arg1	line					572:575	the HEK293 cell line	556:575	the HEK293 cell line	556:575	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	4	12	theme	Recombinant	702:712	arg1	hyaluronidase					714:726	Recombinant hyaluronidase	702:726	Recombinant hyaluronidase	702:726	Recombinant hyaluronidase could resolve highly polymeric hyaluronic acid and also caused dispersal of the cumulus cell layer.
30086619	1	13	theme	cumulus	269:275	arg1	complex					284:290	cumulus oocyte complex	269:290	cumulus oocyte complex	269:290	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	5	14	theme	bovine	937:942	arg1	hyaluronidase					950:962	bovine sperm hyaluronidase	937:962	bovine sperm hyaluronidase	937:962	Comparative analysis with respect to enzyme activity was carried out for the glycosylated and deglycosylated bovine sperm hyaluronidase by N-glycosidase F treatment.
30086619	6	15	theme	hyaluronic	1145:1154	arg1	activity					1156:1163	hyaluronic activity	1145:1163	hyaluronic activity	1145:1163	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	2	16	theme	Asn-X-Ser/Thr	405:417	arg1	motif					419:423	the Asn-X-Ser/Thr motif	401:423	the Asn-X-Ser/Thr motif	401:423	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	2	17	theme	open	459:462	arg1	frame					472:476	the bovine SPAM1 open reading frame	442:476	the bovine SPAM1 open reading frame	442:476	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	5	18	theme	N-glycosidase	967:979	arg1	treatment					983:991	N-glycosidase F treatment	967:991	N-glycosidase F treatment	967:991	Comparative analysis with respect to enzyme activity was carried out for the glycosylated and deglycosylated bovine sperm hyaluronidase by N-glycosidase F treatment.
30086619	3	19	with	assay	670:674	arg1	electrophoresis					685:699	gel electrophoresis	681:699	gel electrophoresis	681:699	Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.
30086619	6	20	theme	significant	1119:1129	arg1	inhibition					1131:1140	significant inhibition	1119:1140	significant inhibition of hyaluronic activity	1119:1163	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	7	21	theme	dispersion	1245:1254	arg1	ability					1256:1262	hyaluronan degradation and cumulus oocyte complex dispersion ability	1195:1262	ability	1256:1262	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	0	22	theme	important	84:92	arg1	motif					108:112	an important Asn-X-Ser/Thr motif	81:112	an important Asn-X-Ser/Thr motif for its activity	81:129	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	4	23	theme	hyaluronic	759:768	arg1	acid					770:773	highly polymeric hyaluronic acid	742:773	highly polymeric hyaluronic acid	742:773	Recombinant hyaluronidase could resolve highly polymeric hyaluronic acid and also caused dispersal of the cumulus cell layer.
30086619	5	24	theme	Comparative	828:838	arg1	analysis					840:847	Comparative analysis	828:847	Comparative analysis with respect to enzyme activity	828:879	Comparative analysis with respect to enzyme activity was carried out for the glycosylated and deglycosylated bovine sperm hyaluronidase by N-glycosidase F treatment.
30086619	1	25	theme	oocyte	277:282	arg1	complex					284:290	cumulus oocyte complex	269:290	cumulus oocyte complex	269:290	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	1	26	from	complex	284:290	arg1	abundant					228:235	abundant	228:235	abundant	228:235	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	4	27	theme	polymeric	749:757	arg1	acid					770:773	highly polymeric hyaluronic acid	742:773	highly polymeric hyaluronic acid	742:773	Recombinant hyaluronidase could resolve highly polymeric hyaluronic acid and also caused dispersal of the cumulus cell layer.
30086619	0	28	theme	bovine	32:37	arg1	hyaluronidase					45:57	recombinant bovine sperm hyaluronidase	20:57	recombinant bovine sperm hyaluronidase	20:57	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	6	29	theme	mutagenesis	1003:1013	arg1	analysis					1015:1022	mutagenesis analysis	1003:1022	mutagenesis analysis	1003:1022	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	5	30	dep	the	901:903	arg1	hyaluronidase					950:962	bovine sperm hyaluronidase	937:962	bovine sperm hyaluronidase	937:962	Comparative analysis with respect to enzyme activity was carried out for the glycosylated and deglycosylated bovine sperm hyaluronidase by N-glycosidase F treatment.
30086619	1	31	theme	hyaluronic	202:211	arg1	acid					213:216	hyaluronic acid	202:216	hyaluronic acid	202:216	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	0	32	theme	recombinant	20:30	arg1	hyaluronidase					45:57	recombinant bovine sperm hyaluronidase	20:57	recombinant bovine sperm hyaluronidase	20:57	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	5	33	theme	F	981:981	arg1	treatment					983:991	N-glycosidase F treatment	967:991	N-glycosidase F treatment	967:991	Comparative analysis with respect to enzyme activity was carried out for the glycosylated and deglycosylated bovine sperm hyaluronidase by N-glycosidase F treatment.
30086619	7	34	theme	cumulus	1222:1228	arg1	ability					1256:1262	hyaluronan degradation and cumulus oocyte complex dispersion ability	1195:1262	ability	1256:1262	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	1	35	theme	acid	213:216	arg1	breakdown					189:197	the breakdown	185:197	the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex	185:290	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	0	36	theme	hyaluronidase	45:57	arg1	Characterization					0:15	Characterization	0:15	Characterization of recombinant bovine sperm hyaluronidase	0:57	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	0	36	theme	hyaluronidase	45:57	arg1	identification					63:76	identification	63:76	identification of an important Asn-X-Ser/Thr motif for its activity	63:129	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	5	37	theme	sperm	944:948	arg1	hyaluronidase					950:962	bovine sperm hyaluronidase	937:962	bovine sperm hyaluronidase	937:962	Comparative analysis with respect to enzyme activity was carried out for the glycosylated and deglycosylated bovine sperm hyaluronidase by N-glycosidase F treatment.
30086619	6	38	gly	glycosylation	1072:1084	arg2	sites					1086:1090	the five potential N-linked glycosylation sites	1044:1090	the five potential N-linked glycosylation sites	1044:1090	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	6	38	gly	glycosylation	1072:1084	arg2	five					1048:1051	five	1048:1051	five	1048:1051	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	5	39	theme	enzyme	865:870	arg1	activity					872:879	enzyme activity	865:879	enzyme activity	865:879	Comparative analysis with respect to enzyme activity was carried out for the glycosylated and deglycosylated bovine sperm hyaluronidase by N-glycosidase F treatment.
30086619	2	40	theme	SPAM1	453:457	arg1	frame					472:476	the bovine SPAM1 open reading frame	442:476	the bovine SPAM1 open reading frame	442:476	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	0	41	theme	sperm	39:43	arg1	hyaluronidase					45:57	recombinant bovine sperm hyaluronidase	20:57	recombinant bovine sperm hyaluronidase	20:57	Characterization of recombinant bovine sperm hyaluronidase and identification of an important Asn-X-Ser/Thr motif for its activity.
30086619	7	42	theme	oocyte	1230:1235	arg1	ability					1256:1262	hyaluronan degradation and cumulus oocyte complex dispersion ability	1195:1262	ability	1256:1262	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	7	43	theme	complex	1237:1243	arg1	ability					1256:1262	hyaluronan degradation and cumulus oocyte complex dispersion ability	1195:1262	ability	1256:1262	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	2	44	theme	bovine	446:451	arg1	frame					472:476	the bovine SPAM1 open reading frame	442:476	the bovine SPAM1 open reading frame	442:476	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	2	45	theme	HEK293	560:565	arg1	line					572:575	the HEK293 cell line	556:575	the HEK293 cell line	556:575	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	7	46	theme	N-linked	1273:1280	arg1	important					1303:1311	important	1303:1311	important	1303:1311	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	7	46	theme	N-linked	1273:1280	arg1	oligosaccharides					1282:1297	the N-linked oligosaccharides	1269:1297	the N-linked oligosaccharides	1269:1297	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	2	47	theme	hyaluronidase	349:361	arg1	activity					312:319	the activity	308:319	the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1)	308:371	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	1	48	from	matrix	258:263	arg1	abundant					228:235	abundant	228:235	abundant	228:235	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	7	49	link	N-linked	1273:1280	arg1	important					1303:1311	important	1303:1311	important	1303:1311	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	7	49	link	N-linked	1273:1280	arg1	oligosaccharides					1282:1297	the N-linked oligosaccharides	1269:1297	the N-linked oligosaccharides	1269:1297	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	2	50	from	effect	391:396	arg1	activity					432:439	its activity	428:439	its activity	428:439	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	2	51	theme	sperm	343:347	arg1	hyaluronidase					349:361	recombinant bovine sperm hyaluronidase 1	324:363	recombinant bovine sperm hyaluronidase 1 (SPAM1)	324:371	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	2	51	theme	sperm	343:347	arg1	SPAM1					366:370	SPAM1	366:370	SPAM1	366:370	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	4	52	theme	cell	816:819	arg1	layer					821:825	the cumulus cell layer	804:825	the cumulus cell layer	804:825	Recombinant hyaluronidase could resolve highly polymeric hyaluronic acid and also caused dispersal of the cumulus cell layer.
30086619	4	53	theme	cumulus	808:814	arg1	layer					821:825	the cumulus cell layer	804:825	the cumulus cell layer	804:825	Recombinant hyaluronidase could resolve highly polymeric hyaluronic acid and also caused dispersal of the cumulus cell layer.
30086619	3	54	theme	bovine	604:609	arg1	hyaluronidase					611:623	recombinant bovine hyaluronidase	592:623	recombinant bovine hyaluronidase	592:623	Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.
30086619	2	55	theme	bovine	336:341	arg1	hyaluronidase					349:361	recombinant bovine sperm hyaluronidase 1	324:363	recombinant bovine sperm hyaluronidase 1 (SPAM1)	324:371	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	2	55	theme	bovine	336:341	arg1	SPAM1					366:370	SPAM1	366:370	SPAM1	366:370	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	6	56	link	N-linked	1063:1070	arg1	sites					1086:1090	the five potential N-linked glycosylation sites	1044:1090	the five potential N-linked glycosylation sites	1044:1090	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	1	57	from	abundant	228:235	arg1	matrix					258:263	the extracellular matrix	240:263	the extracellular matrix	240:263	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	1	57	from	abundant	228:235	arg1	complex					284:290	cumulus oocyte complex	269:290	cumulus oocyte complex	269:290	Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex.
30086619	3	58	theme	hyaluronidase	647:659	arg1	assay					670:674	a hyaluronidase activity assay	645:674	a hyaluronidase activity assay with gel electrophoresis	645:699	Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.
30086619	3	59	theme	hyaluronidase	611:623	arg1	Expression					578:587	Expression	578:587	Expression of recombinant bovine hyaluronidase	578:623	Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.
30086619	2	60	theme	recombinant	324:334	arg1	hyaluronidase					349:361	recombinant bovine sperm hyaluronidase 1	324:363	recombinant bovine sperm hyaluronidase 1 (SPAM1)	324:371	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	2	60	theme	recombinant	324:334	arg1	SPAM1					366:370	SPAM1	366:370	SPAM1	366:370	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	6	61	theme	N-linked	1063:1070	arg1	sites					1086:1090	the five potential N-linked glycosylation sites	1044:1090	the five potential N-linked glycosylation sites	1044:1090	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	3	62	theme	activity	661:668	arg1	assay					670:674	a hyaluronidase activity assay	645:674	a hyaluronidase activity assay with gel electrophoresis	645:699	Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.
30086619	4	63	theme	layer	821:825	arg1	dispersal					791:799	dispersal	791:799	dispersal of the cumulus cell layer	791:825	Recombinant hyaluronidase could resolve highly polymeric hyaluronic acid and also caused dispersal of the cumulus cell layer.
30086619	2	64	theme	motif	419:423	arg1	effect					391:396	the effect	387:396	the effect of the Asn-X-Ser/Thr motif on its activity	387:439	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
30086619	7	65	theme	hyaluronidase	1386:1398	arg1	commercialization					1365:1381	the commercialization	1361:1381	the commercialization of hyaluronidase	1361:1398	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	6	66	theme	potential	1053:1061	arg1	sites					1086:1090	the five potential N-linked glycosylation sites	1044:1090	the five potential N-linked glycosylation sites	1044:1090	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	7	67	theme	hyaluronan	1195:1204	arg1	degradation					1206:1216	hyaluronan degradation and cumulus oocyte complex dispersion ability	1195:1262	degradation	1206:1216	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	3	68	theme	recombinant	592:602	arg1	hyaluronidase					611:623	recombinant bovine hyaluronidase	592:623	recombinant bovine hyaluronidase	592:623	Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.
30086619	6	69	theme	glycosylation	1072:1084	arg1	sites					1086:1090	the five potential N-linked glycosylation sites	1044:1090	the five potential N-linked glycosylation sites	1044:1090	Finally, mutagenesis analysis revealed that among the five potential N-linked glycosylation sites, only three contributed to significant inhibition of hyaluronic activity.
30086619	7	70	theme	enzyme	1317:1322	arg1	activity					1324:1331	enzyme activity	1317:1331	enzyme activity	1317:1331	Recombinant bovine SPAM1 has hyaluronan degradation and cumulus oocyte complex dispersion ability, and the N-linked oligosaccharides are important for enzyme activity, providing a foundation for the commercialization of hyaluronidase.
30086619	2	71	theme	mammalian	498:506	arg1	vector					519:524	the mammalian expression vector	494:524	the mammalian expression vector pCXN2	494:530	To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line.
29621585	0	0	theme	cell	72:75	arg1	antigen-2					77:85	bone marrow stromal cell antigen-2	52:85	bone marrow stromal cell antigen-2	52:85	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	9	1	theme	characterization	1124:1139	arg1	study					1077:1081	This study	1072:1081	This study	1072:1081	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	1	theme	characterization	1124:1139	arg1	report					1096:1101	the first report	1086:1101	the first report of the isolation and characterization of BST-2 from C. nippon	1086:1163	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	1	2	from	cells	276:280	arg1	range					235:239	a wide range	228:239	a wide range of enveloped viruses from infected cells	228:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	1	2	from	cells	276:280	arg1	viruses					254:260	enveloped viruses	244:260	enveloped viruses from infected cells	244:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	0	3	theme	stromal	64:70	arg1	antigen-2					77:85	bone marrow stromal cell antigen-2	52:85	bone marrow stromal cell antigen-2	52:85	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	6	4	theme	cell	790:793	arg1	surface					795:801	the cell surface	786:801	the cell surface	786:801	cnBST-2 was shown to be expressed on the cell surface, like human BST-2.
29621585	9	5	theme	first	1090:1094	arg1	study					1077:1081	This study	1072:1081	This study	1072:1081	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	5	theme	first	1090:1094	arg1	report					1096:1101	the first report	1086:1101	the first report of the isolation and characterization of BST-2 from C. nippon	1086:1163	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	6	dep	isolation	1110:1118	arg1	the					1106:1108	the	1106:1108	the	1106:1108	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	7	theme	BST-2	1144:1148	arg1	characterization					1124:1139	characterization	1124:1139	characterization	1124:1139	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	7	theme	BST-2	1144:1148	arg1	isolation					1110:1118	isolation	1110:1118	isolation	1110:1118	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	7	8	theme	cnBST-2	846:852	arg1	expression					832:841	Exogenous expression	822:841	Exogenous expression of cnBST-2	822:852	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	0	9	theme	antigen-2	77:85	arg1	identification					9:22	identification	9:22	identification	9:22	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	0	9	theme	antigen-2	77:85	arg1	Cloning					0:6	Cloning	0:6	Cloning	0:6	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	0	9	theme	antigen-2	77:85	arg1	analysis					40:47	functional analysis	29:47	functional analysis	29:47	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	9	10	from	report	1096:1101	arg1	nippon					1158:1163	nippon	1158:1163	nippon	1158:1163	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	7	11	theme	Exogenous	822:830	arg1	expression					832:841	Exogenous expression	822:841	Exogenous expression of cnBST-2	822:852	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	1	12	theme	wide	230:233	arg1	range					235:239	a wide range	228:239	a wide range of enveloped viruses from infected cells	228:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	5	13	theme	potential	719:727	arg1	sites					742:746	three potential dimerization sites	713:746	three potential dimerization sites	713:746	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	4	14	theme	%	544:544	arg1	identity					546:553	37.8% and 74.2% identity	530:553	37.8% and 74.2% identity	530:553	cnBST-2 shares 37.8% and 74.2% identity with the BST-2 homologs from Homo sapiens and Ovis aries, respectively.
29621585	0	15	theme	sika	92:95	arg1	nippon					110:115	Cervus nippon	103:115	Cervus nippon	103:115	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	0	15	theme	sika	92:95	arg1	deer					97:100	sika deer	92:100	sika deer (Cervus nippon)	92:116	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	5	16	theme	cnBST-2	655:661	arg1	cnBST-2					655:661	cnBST-2	655:661	cnBST-2	655:661	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	16	theme	cnBST-2	655:661	arg1	domain					645:650	The extracellular domain	627:650	The extracellular domain of cnBST-2	627:661	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	17	theme	N-linked	680:687	arg1	sites					703:707	two putative N-linked glycosylation sites	667:707	two putative N-linked glycosylation sites	667:707	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	1	18	from	range	235:239	arg1	cells					276:280	infected cells	267:280	infected cells	267:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	3	19	theme	homolog	475:481	arg1	protein					454:460	the protein	450:460	the protein of the BST-2 homolog from sika deer (Cervus nippon)	450:512	In this study, we cloned the gene and characterized the protein of the BST-2 homolog from sika deer (Cervus nippon).
29621585	5	20	theme	glycosylation	689:701	arg1	sites					703:707	two putative N-linked glycosylation sites	667:707	two putative N-linked glycosylation sites	667:707	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	1	21	theme	range	235:239	arg1	release					217:223	the release	213:223	the release of a wide range of enveloped viruses from infected cells	213:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	9	22	theme	isolation	1110:1118	arg1	study					1077:1081	This study	1072:1081	This study	1072:1081	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	22	theme	isolation	1110:1118	arg1	report					1096:1101	the first report	1086:1101	the first report of the isolation and characterization of BST-2 from C. nippon	1086:1163	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	7	23	from	inhibition	873:882	arg1	cells					918:922	293T cells	913:922	293T cells	913:922	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	8	24	theme	nuclear	1025:1031	arg1	factor-κB					1033:1041	nuclear factor-κB	1025:1041	nuclear factor-κB	1025:1041	Moreover, cnBST-2 was not able to activate nuclear factor-κB, in contrast to human BST-2.
29621585	0	25	theme	Cervus	103:108	arg1	nippon					110:115	Cervus nippon	103:115	Cervus nippon	103:115	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	0	25	theme	Cervus	103:108	arg1	deer					97:100	sika deer	92:100	sika deer (Cervus nippon)	92:116	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	4	26	from	aries	606:610	arg1	homologs					570:577	the BST-2 homologs	560:577	the BST-2 homologs from Homo sapiens and Ovis aries	560:610	cnBST-2 shares 37.8% and 74.2% identity with the BST-2 homologs from Homo sapiens and Ovis aries, respectively.
29621585	3	27	from	deer	493:496	arg1	protein					454:460	the protein	450:460	the protein of the BST-2 homolog from sika deer (Cervus nippon)	450:512	In this study, we cloned the gene and characterized the protein of the BST-2 homolog from sika deer (Cervus nippon).
29621585	1	28	theme	enveloped	244:252	arg1	viruses					254:260	enveloped viruses	244:260	enveloped viruses from infected cells	244:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	3	29	theme	BST-2	469:473	arg1	homolog					475:481	the BST-2 homolog	465:481	the BST-2 homolog	465:481	In this study, we cloned the gene and characterized the protein of the BST-2 homolog from sika deer (Cervus nippon).
29621585	4	30	theme	BST-2	564:568	arg1	homologs					570:577	the BST-2 homologs	560:577	the BST-2 homologs from Homo sapiens and Ovis aries	560:610	cnBST-2 shares 37.8% and 74.2% identity with the BST-2 homologs from Homo sapiens and Ovis aries, respectively.
29621585	0	31	theme	functional	29:38	arg1	analysis					40:47	functional analysis	29:47	functional analysis	29:47	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	1	32	theme	viruses	254:260	arg1	range					235:239	a wide range	228:239	a wide range of enveloped viruses from infected cells	228:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	8	33	dep	BST-2	1065:1069	arg1	contrast					1047:1054	contrast	1047:1054	contrast	1047:1054	Moreover, cnBST-2 was not able to activate nuclear factor-κB, in contrast to human BST-2.
29621585	5	34	theme	dimerization	729:740	arg1	sites					742:746	three potential dimerization sites	713:746	three potential dimerization sites	713:746	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	35	gly	glycosylation	689:701	arg2	sites					703:707	two putative N-linked glycosylation sites	667:707	two putative N-linked glycosylation sites	667:707	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	35	gly	glycosylation	689:701	arg2	two					667:669	two	667:669	two	667:669	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	1	36	theme	cellular	173:180	arg1	BST-2					119:123	BST-2	119:123	BST-2(tetherin/CD317/HM1.24)	119:146	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	1	36	theme	cellular	173:180	arg1	factor					192:197	a cellular antiviral factor	171:197	a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells	171:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	8	37	theme	human	1059:1063	arg1	BST-2					1065:1069	human BST-2	1059:1069	human BST-2	1059:1069	Moreover, cnBST-2 was not able to activate nuclear factor-κB, in contrast to human BST-2.
29621585	3	38	theme	Cervus	499:504	arg1	deer					493:496	sika deer	488:496	sika deer (Cervus nippon)	488:512	In this study, we cloned the gene and characterized the protein of the BST-2 homolog from sika deer (Cervus nippon).
29621585	3	38	theme	Cervus	499:504	arg1	nippon					506:511	Cervus nippon	499:511	Cervus nippon	499:511	In this study, we cloned the gene and characterized the protein of the BST-2 homolog from sika deer (Cervus nippon).
29621585	7	39	theme	particle	893:900	arg1	release					902:908	HIV-1 particle release	887:908	HIV-1 particle release	887:908	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	1	40	theme	antiviral	182:190	arg1	BST-2					119:123	BST-2	119:123	BST-2(tetherin/CD317/HM1.24)	119:146	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	1	40	theme	antiviral	182:190	arg1	factor					192:197	a cellular antiviral factor	171:197	a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells	171:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	1	41	theme	infected	267:274	arg1	cells					276:280	infected cells	267:280	infected cells	267:280	BST-2(tetherin/CD317/HM1.24) has been identified as a cellular antiviral factor that inhibits the release of a wide range of enveloped viruses from infected cells.
29621585	5	42	theme	extracellular	631:643	arg1	cnBST-2					655:661	cnBST-2	655:661	cnBST-2	655:661	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	42	theme	extracellular	631:643	arg1	domain					645:650	The extracellular domain	627:650	The extracellular domain of cnBST-2	627:661	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	3	43	theme	sika	488:491	arg1	deer					493:496	sika deer	488:496	sika deer (Cervus nippon)	488:512	In this study, we cloned the gene and characterized the protein of the BST-2 homolog from sika deer (Cervus nippon).
29621585	3	43	theme	sika	488:491	arg1	nippon					506:511	Cervus nippon	499:511	Cervus nippon	499:511	In this study, we cloned the gene and characterized the protein of the BST-2 homolog from sika deer (Cervus nippon).
29621585	7	44	theme	release	902:908	arg1	inhibition					873:882	potent inhibition	866:882	potent inhibition of HIV-1 particle release in 293T cells	866:922	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	5	45	theme	putative	671:678	arg1	sites					703:707	two putative N-linked glycosylation sites	667:707	two putative N-linked glycosylation sites	667:707	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	6	46	theme	human	809:813	arg1	BST-2					815:819	human BST-2	809:819	human BST-2	809:819	cnBST-2 was shown to be expressed on the cell surface, like human BST-2.
29621585	0	47	from	deer	97:100	arg1	identification					9:22	identification	9:22	identification	9:22	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	0	47	from	deer	97:100	arg1	Cloning					0:6	Cloning	0:6	Cloning	0:6	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	0	47	from	deer	97:100	arg1	analysis					40:47	functional analysis	29:47	functional analysis	29:47	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	7	48	theme	HIV-1	971:975	arg1	Vpu					977:979	HIV-1 Vpu	971:979	HIV-1 Vpu	971:979	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	2	49	theme	BST-2	296:300	arg1	Orthologs					283:291	Orthologs	283:291	Orthologs of BST-2	283:300	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	7	50	theme	HIV-1	887:891	arg1	release					902:908	HIV-1 particle release	887:908	HIV-1 particle release	887:908	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	4	51	theme	Ovis	601:604	arg1	aries					606:610	Ovis aries	601:610	Ovis aries	601:610	cnBST-2 shares 37.8% and 74.2% identity with the BST-2 homologs from Homo sapiens and Ovis aries, respectively.
29621585	7	52	theme	293T	913:916	arg1	cells					918:922	293T cells	913:922	293T cells	913:922	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	5	53	contain	has	663:665	arg2	sites					742:746	three potential dimerization sites	713:746	three potential dimerization sites	713:746	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	53	contain	has	663:665	arg1	cnBST-2					655:661	cnBST-2	655:661	cnBST-2	655:661	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	53	contain	has	663:665	arg2	sites					703:707	two putative N-linked glycosylation sites	667:707	two putative N-linked glycosylation sites	667:707	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	5	53	contain	has	663:665	arg1	domain					645:650	The extracellular domain	627:650	The extracellular domain of cnBST-2	627:661	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	7	54	theme	potent	866:871	arg1	inhibition					873:882	potent inhibition	866:882	potent inhibition of HIV-1 particle release in 293T cells	866:922	Exogenous expression of cnBST-2 resulted in potent inhibition of HIV-1 particle release in 293T cells; however, this activity resisted antagonism by HIV-1 Vpu.
29621585	4	55	from	sapiens	589:595	arg1	homologs					570:577	the BST-2 homologs	560:577	the BST-2 homologs from Homo sapiens and Ovis aries	560:610	cnBST-2 shares 37.8% and 74.2% identity with the BST-2 homologs from Homo sapiens and Ovis aries, respectively.
29621585	0	56	theme	marrow	57:62	arg1	antigen-2					77:85	bone marrow stromal cell antigen-2	52:85	bone marrow stromal cell antigen-2	52:85	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	4	57	theme	%	534:534	arg1	identity					546:553	37.8% and 74.2% identity	530:553	37.8% and 74.2% identity	530:553	cnBST-2 shares 37.8% and 74.2% identity with the BST-2 homologs from Homo sapiens and Ovis aries, respectively.
29621585	5	58	link	N-linked	680:687	arg1	sites					703:707	two putative N-linked glycosylation sites	667:707	two putative N-linked glycosylation sites	667:707	The extracellular domain of cnBST-2 has two putative N-linked glycosylation sites and three potential dimerization sites.
29621585	2	59	theme	several	326:332	arg1	humans					352:357	humans	352:357	humans	352:357	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	2	59	theme	several	326:332	arg1	sheep					375:379	sheep	375:379	sheep	375:379	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	2	59	theme	several	326:332	arg1	pigs					382:385	pigs	382:385	pigs	382:385	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	2	59	theme	several	326:332	arg1	monkeys					360:366	monkeys	360:366	monkeys	360:366	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	2	59	theme	several	326:332	arg1	cows					369:372	cows	369:372	cows	369:372	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	2	59	theme	several	326:332	arg1	mice					392:395	mice	392:395	mice	392:395	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	2	59	theme	several	326:332	arg1	species					334:340	several species	326:340	several species including humans, monkeys, cows, sheep, pigs, and mice	326:395	Orthologs of BST-2 have been identified in several species including humans, monkeys, cows, sheep, pigs, and mice.
29621585	0	60	theme	bone	52:55	arg1	marrow					57:62	bone marrow	52:62	bone marrow stromal cell antigen-2	52:85	Cloning, identification, and functional analysis of bone marrow stromal cell antigen-2 from sika deer (Cervus nippon).
29621585	9	61	from	nippon	1158:1163	arg1	study					1077:1081	This study	1072:1081	This study	1072:1081	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	61	from	nippon	1158:1163	arg1	characterization					1124:1139	characterization	1124:1139	characterization	1124:1139	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	61	from	nippon	1158:1163	arg1	report					1096:1101	the first report	1086:1101	the first report of the isolation and characterization of BST-2 from C. nippon	1086:1163	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	9	61	from	nippon	1158:1163	arg1	isolation					1110:1118	isolation	1110:1118	isolation	1110:1118	This study is the first report of the isolation and characterization of BST-2 from C. nippon.
29621585	4	62	theme	Homo	584:587	arg1	sapiens					589:595	Homo sapiens	584:595	Homo sapiens	584:595	cnBST-2 shares 37.8% and 74.2% identity with the BST-2 homologs from Homo sapiens and Ovis aries, respectively.
28657654	0	0	theme	proteins	105:112	arg1	O-GlcNAcylation					43:57	altered O-GlcNAcylation	35:57	altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease	35:135	Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease.
28657654	7	1	theme	AD	1502:1503	arg1	development					1478:1488	the development	1474:1488	the development of sporadic AD	1474:1503	These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD.
28657654	6	2	theme	memory-associated	1339:1355	arg1	proteins					1357:1364	memory-associated proteins	1339:1364	memory-associated proteins	1339:1364	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	9	3	theme	&	1598:1598	arg1	Sons					1600:1603	John Wiley & Sons	1587:1603	John Wiley & Sons	1587:1603	Published by John Wiley & Sons, Ltd.
28657654	2	4	from	O-GlcNAcylation	588:602	arg1	tissues					630:636	postmortem human brain tissues	607:636	postmortem human brain tissues	607:636	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	0	5	theme	memory-associated	87:103	arg1	proteins					105:112	structural, synaptic and memory-associated proteins	62:112	structural, synaptic and memory-associated proteins	62:112	Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease.
28657654	1	6	theme	important	350:358	arg1	modification					387:398	this important protein post-translational modification	345:398	this important protein post-translational modification at the proteome level	345:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	7	from	characterization	325:340	arg1	level					416:420	the proteome level	403:420	the proteome level	403:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	2	8	theme	isobaric	672:679	arg1	mass					688:691	isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry	672:802	mass	688:691	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	5	9	theme	peptide	1092:1098	arg1	abundance					1100:1108	O-GlcNAc peptide abundance	1083:1108	O-GlcNAc peptide abundance	1083:1108	Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes.
28657654	1	10	theme	protein	360:366	arg1	modification					387:398	this important protein post-translational modification	345:398	this important protein post-translational modification at the proteome level	345:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	2	11	theme	brain	624:628	arg1	tissues					630:636	postmortem human brain tissues	607:636	postmortem human brain tissues	607:636	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	7	12	theme	proteins	1446:1453	arg1	O-GlcNAcylation					1412:1426	O-GlcNAcylation	1412:1426	O-GlcNAcylation of multiple brain proteins	1412:1453	These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD.
28657654	9	13	dep	Published	1574:1582	arg1	Ltd.					1606:1609	Ltd.	1606:1609	Ltd.	1606:1609	Published by John Wiley & Sons, Ltd.
28657654	2	14	theme	comprehensive	528:540	arg1	analysis					567:574	the most comprehensive, quantitative proteomics analysis	519:574	the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry	519:802	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	1	15	theme	post-translational	368:385	arg1	modification					387:398	this important protein post-translational modification	345:398	this important protein post-translational modification at the proteome level	345:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	2	16	theme	human	618:622	arg1	tissues					630:636	postmortem human brain tissues	607:636	postmortem human brain tissues	607:636	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	1	17	theme	low	464:466	arg1	stoichiometry					468:480	low stoichiometry	464:480	low stoichiometry	464:480	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	3	18	theme	O-GlcNAcylation	853:867	arg1	sites					869:873	1094 O-GlcNAcylation sites	848:873	1094 O-GlcNAcylation sites	848:873	A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain.
28657654	1	19	theme	modification	387:398	arg1	characterization					325:340	detailed molecular characterization	306:340	detailed molecular characterization of this important protein post-translational modification at the proteome level	306:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	6	20	theme	cytoskeleton	1312:1323	arg1	proteins					1325:1332	cytoskeleton proteins	1312:1332	cytoskeleton proteins	1312:1332	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	21	theme	O-GlcNAcylated	1203:1216	arg1	proteins					1218:1225	The altered O-GlcNAcylated proteins	1191:1225	The altered O-GlcNAcylated proteins	1191:1225	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	2	22	theme	mass	786:789	arg1	spectrometry					791:802	mass spectrometry	786:802	mass spectrometry	786:802	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	6	23	theme	structural	1245:1254	arg1	categories					1271:1280	several structural and functional categories	1237:1280	several structural and functional categories	1237:1280	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	23	theme	structural	1245:1254	arg1	proteins					1357:1364	memory-associated proteins	1339:1364	memory-associated proteins	1339:1364	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	23	theme	structural	1245:1254	arg1	proteins					1302:1309	synaptic proteins	1293:1309	synaptic proteins	1293:1309	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	23	theme	structural	1245:1254	arg1	proteins					1325:1332	cytoskeleton proteins	1312:1332	cytoskeleton proteins	1312:1332	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	1	24	from	level	416:420	arg1	modification					387:398	this important protein post-translational modification	345:398	this important protein post-translational modification at the proteome level	345:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	24	from	level	416:420	arg1	characterization					325:340	detailed molecular characterization	306:340	detailed molecular characterization of this important protein post-translational modification at the proteome level	306:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	9	25	theme	John	1587:1590	arg1	Sons					1600:1603	John Wiley & Sons	1587:1603	John Wiley & Sons	1587:1603	Published by John Wiley & Sons, Ltd.
28657654	6	26	theme	altered	1195:1201	arg1	proteins					1218:1225	The altered O-GlcNAcylated proteins	1191:1225	The altered O-GlcNAcylated proteins	1191:1225	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	5	27	theme	O-GlcNAcylation	1138:1152	arg1	level					1154:1158	O-GlcNAcylation level	1138:1158	O-GlcNAcylation level than to protein level changes	1138:1188	Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes.
28657654	1	28	theme	labile	486:491	arg1	nature					493:498	labile nature	486:498	labile nature	486:498	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	2	29	theme	proteomics	556:565	arg1	analysis					567:574	the most comprehensive, quantitative proteomics analysis	519:574	the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry	519:802	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	0	30	theme	Quantitative	0:11	arg1	proteomics					13:22	Quantitative proteomics	0:22	Quantitative proteomics	0:22	Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease.
28657654	6	31	theme	synaptic	1293:1300	arg1	proteins					1302:1309	synaptic proteins	1293:1309	synaptic proteins	1293:1309	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	2	32	theme	mass	688:691	arg1	use					665:667	the use	661:667	the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry	661:802	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	7	33	theme	brain	1440:1444	arg1	proteins					1446:1453	multiple brain proteins	1431:1453	multiple brain proteins	1431:1453	These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD.
28657654	0	34	theme	altered	35:41	arg1	O-GlcNAcylation					43:57	altered O-GlcNAcylation	35:57	altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease	35:135	Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease.
28657654	6	35	theme	several	1237:1243	arg1	categories					1271:1280	several structural and functional categories	1237:1280	several structural and functional categories	1237:1280	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	35	theme	several	1237:1243	arg1	proteins					1357:1364	memory-associated proteins	1339:1364	memory-associated proteins	1339:1364	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	35	theme	several	1237:1243	arg1	proteins					1302:1309	synaptic proteins	1293:1309	synaptic proteins	1293:1309	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	35	theme	several	1237:1243	arg1	proteins					1325:1332	cytoskeleton proteins	1312:1332	cytoskeleton proteins	1312:1332	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	4	36	theme	O-GlcNAc	956:963	arg1	peptides					965:972	thirty-one O-GlcNAc peptides	945:972	thirty-one O-GlcNAc peptides covering 81 proteins	945:993	One hundred and thirty-one O-GlcNAc peptides covering 81 proteins were altered in AD brains as compared with controls (q < 0.05).
28657654	2	37	theme	tandem	681:686	arg1	mass					688:691	isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry	672:802	mass	688:691	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	4	38	theme	thirty-one	945:954	arg1	peptides					965:972	thirty-one O-GlcNAc peptides	945:972	thirty-one O-GlcNAc peptides covering 81 proteins	945:993	One hundred and thirty-one O-GlcNAc peptides covering 81 proteins were altered in AD brains as compared with controls (q < 0.05).
28657654	1	39	theme	proteome	407:414	arg1	level					416:420	the proteome level	403:420	the proteome level	403:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	40	theme	important	222:230	arg1	factor					232:237	an important factor	219:237	an important factor in the pathogenesis of sporadic Alzheimer's disease (AD)	219:294	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	41	link	O-linked	162:169	arg1	β-N-acetylglucosamine					171:191	O-linked β-N-acetylglucosamine	162:191	O-linked β-N-acetylglucosamine (O-GlcNAc)	162:202	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	41	link	O-linked	162:169	arg1	O-GlcNAc					194:201	O-GlcNAc	194:201	O-GlcNAc	194:201	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	5	42	theme	abundance	1100:1108	arg1	alteration					1069:1078	alteration	1069:1078	alteration of O-GlcNAc peptide abundance	1069:1108	Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes.
28657654	3	43	theme	530	896:898	arg1	proteins					900:907	530 proteins	896:907	530 proteins	896:907	A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain.
28657654	5	44	theme	level	1176:1180	arg1	changes					1182:1188	protein level changes	1168:1188	protein level changes	1168:1188	Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes.
28657654	2	45	dep	comprehensive	528:540	arg1	quantitative					543:554	quantitative	543:554	quantitative	543:554	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	1	46	from	factor	232:237	arg1	pathogenesis					246:257	the pathogenesis	242:257	the pathogenesis of sporadic Alzheimer's disease (AD)	242:294	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	47	theme	detailed	306:313	arg1	characterization					325:340	detailed molecular characterization	306:340	detailed molecular characterization of this important protein post-translational modification at the proteome level	306:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	2	48	theme	postmortem	607:616	arg1	tissues					630:636	postmortem human brain tissues	607:636	postmortem human brain tissues	607:636	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	7	49	theme	O-GlcNAcylation	1412:1426	arg1	dysregulation					1395:1407	dysregulation	1395:1407	dysregulation of O-GlcNAcylation of multiple brain proteins	1395:1453	These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD.
28657654	2	50	theme	photocleavage	723:735	arg1	enrichment					737:746	chemoenzymatic photocleavage enrichment	708:746	chemoenzymatic photocleavage enrichment	708:746	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	0	51	theme	structural	62:71	arg1	proteins					105:112	structural, synaptic and memory-associated proteins	62:112	structural, synaptic and memory-associated proteins	62:112	Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease.
28657654	1	52	theme	molecular	315:323	arg1	characterization					325:340	detailed molecular characterization	306:340	detailed molecular characterization of this important protein post-translational modification at the proteome level	306:420	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	8	53	theme	Great	1547:1551	arg1	Britain					1553:1559	Great Britain	1547:1559	Great Britain	1547:1559	Copyright © 2017 Pathological Society of Great Britain and Ireland.
28657654	6	54	theme	functional	1260:1269	arg1	categories					1271:1280	several structural and functional categories	1237:1280	several structural and functional categories	1237:1280	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	54	theme	functional	1260:1269	arg1	proteins					1357:1364	memory-associated proteins	1339:1364	memory-associated proteins	1339:1364	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	54	theme	functional	1260:1269	arg1	proteins					1302:1309	synaptic proteins	1293:1309	synaptic proteins	1293:1309	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	6	54	theme	functional	1260:1269	arg1	proteins					1325:1332	cytoskeleton proteins	1312:1332	cytoskeleton proteins	1312:1332	The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins.
28657654	2	55	theme	chemoenzymatic	708:721	arg1	enrichment					737:746	chemoenzymatic photocleavage enrichment	708:746	chemoenzymatic photocleavage enrichment	708:746	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	1	56	theme	Protein	138:144	arg1	modification					146:157	Protein modification	138:157	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc)	138:202	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	2	57	dep	mass	688:691	arg1	labelling					697:705	tag labelling	693:705	tag labelling	693:705	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	7	58	theme	multiple	1431:1438	arg1	proteins					1446:1453	multiple brain proteins	1431:1453	multiple brain proteins	1431:1453	These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD.
28657654	7	59	theme	sporadic	1493:1500	arg1	AD					1502:1503	sporadic AD	1493:1503	sporadic AD	1493:1503	These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD.
28657654	3	60	theme	peptides	830:837	arg1	total					807:811	A total	805:811	A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites	805:873	A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain.
28657654	2	61	theme	protein	580:586	arg1	O-GlcNAcylation					588:602	protein O-GlcNAcylation	580:602	protein O-GlcNAcylation in postmortem human brain tissues with and without AD	580:656	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	2	62	theme	enrichment	737:746	arg1	use					665:667	the use	661:667	the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry	661:802	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	2	63	theme	chromatography	760:773	arg1	use					665:667	the use	661:667	the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry	661:802	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	2	64	theme	tag	693:695	arg1	labelling					697:705	tag labelling	693:705	tag labelling	693:705	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	4	65	theme	AD	1011:1012	arg1	brains					1014:1019	AD brains	1011:1019	AD brains	1011:1019	One hundred and thirty-one O-GlcNAc peptides covering 81 proteins were altered in AD brains as compared with controls (q < 0.05).
28657654	5	66	theme	O-GlcNAc	1083:1090	arg1	abundance					1100:1108	O-GlcNAc peptide abundance	1083:1108	O-GlcNAc peptide abundance	1083:1108	Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes.
28657654	5	67	theme	protein	1168:1174	arg1	changes					1182:1188	protein level changes	1168:1188	protein level changes	1168:1188	Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes.
28657654	2	68	theme	liquid	753:758	arg1	chromatography					760:773	liquid chromatography	753:773	liquid chromatography coupled to mass spectrometry	753:802	Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry.
28657654	1	69	theme	O-linked	162:169	arg1	β-N-acetylglucosamine					171:191	O-linked β-N-acetylglucosamine	162:191	O-linked β-N-acetylglucosamine (O-GlcNAc)	162:202	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	69	theme	O-linked	162:169	arg1	O-GlcNAc					194:201	O-GlcNAc	194:201	O-GlcNAc	194:201	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	3	70	theme	1850	816:819	arg1	peptides					830:837	1850 O-GlcNAc peptides	816:837	1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites	816:873	A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain.
28657654	0	71	theme	synaptic	74:81	arg1	proteins					105:112	structural, synaptic and memory-associated proteins	62:112	structural, synaptic and memory-associated proteins	62:112	Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease.
28657654	3	72	theme	O-GlcNAc	821:828	arg1	peptides					830:837	1850 O-GlcNAc peptides	816:837	1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites	816:873	A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain.
28657654	9	73	theme	Wiley	1592:1596	arg1	Sons					1600:1603	John Wiley & Sons	1587:1603	John Wiley & Sons	1587:1603	Published by John Wiley & Sons, Ltd.
28657654	3	74	theme	human	916:920	arg1	brain					922:926	the human brain	912:926	the human brain	912:926	A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain.
28657654	1	75	theme	sporadic	262:269	arg1	AD					292:293	AD	292:293	AD	292:293	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
28657654	1	75	theme	sporadic	262:269	arg1	disease					283:289	sporadic Alzheimer's disease	262:289	sporadic Alzheimer's disease (AD)	262:294	Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature.
27912985	7	0	theme	Pfs48/45	1194:1201	arg1	immunogenicity					1172:1185	improved functional immunogenicity	1152:1185	improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact)	1152:1232	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	1	theme	N-glycosylation	1289:1303	arg1	sites					1305:1309	all N-glycosylation sites	1285:1309	all N-glycosylation sites mutated	1285:1317	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	4	2	theme	reducing	704:711	arg1	responses					720:728	significant transmission reducing immune responses	679:728	significant transmission reducing immune responses	679:728	In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses.
27912985	3	3	theme	folded	499:504	arg1	Pfs48/45					527:534	a fully folded, functionally active Pfs48/45	491:534	a fully folded, functionally active Pfs48/45	491:534	However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms.
27912985	9	4	theme	different	1711:1719	arg1	stages					1732:1737	different life cycle stages	1711:1737	different life cycle stages	1711:1737	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	1	5	theme	leading	173:179	arg1	Pfs25					163:167	Pfs25	163:167	Pfs25	163:167	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	1	5	theme	leading	173:179	arg1	candidates					181:190	leading candidates	173:190	leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV)	173:272	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	1	5	theme	leading	173:179	arg1	Pfs48/45					150:157	Pfs48/45	150:157	Pfs48/45	150:157	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	2	6	from	presentation	336:347	arg1	stages					325:330	the erythrocytic sexual stages	301:330	the erythrocytic sexual stages	301:330	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	2	6	from	presentation	336:347	arg1	host					400:403	the human host	390:403	the human host	390:403	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	8	7	theme	reducing	1503:1510	arg1	capabilities					1512:1523	transmission reducing capabilities	1490:1523	transmission reducing capabilities of all four DNA vaccines	1490:1548	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	9	8	theme	plasmids	1599:1606	arg1	combination					1580:1590	a combination	1578:1590	a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25)	1578:1635	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	2	9	theme	erythrocytic	305:316	arg1	stages					325:330	the erythrocytic sexual stages	301:330	the erythrocytic sexual stages	301:330	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	3	10	theme	expression	559:568	arg1	platforms					570:578	various protein expression platforms	543:578	various protein expression platforms	543:578	However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms.
27912985	0	11	theme	DNA	90:92	arg1	vaccines					94:101	DNA vaccines	90:101	DNA vaccines administered by intramuscular electroporation	90:147	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	3	12	theme	various	543:549	arg1	platforms					570:578	various protein expression platforms	543:578	various protein expression platforms	543:578	However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms.
27912985	4	13	theme	transmission	691:702	arg1	responses					720:728	significant transmission reducing immune responses	679:728	significant transmission reducing immune responses	679:728	In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses.
27912985	6	14	theme	antibody	998:1005	arg1	titers					1007:1012	antibody titers	998:1012	antibody titers	998:1012	EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine.
27912985	6	15	theme	DNA	1092:1094	arg1	vaccine					1096:1102	SYN Pfs48/45 DNA vaccine	1079:1102	SYN Pfs48/45 DNA vaccine	1079:1102	EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine.
27912985	7	16	theme	Mosquito	1105:1112	arg1	assays					1131:1136	Mosquito membrane feeding assays	1105:1136	Mosquito membrane feeding assays	1105:1136	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	8	17	theme	DNA	1537:1539	arg1	vaccines					1541:1548	all four DNA vaccines	1528:1548	all four DNA vaccines	1528:1548	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	9	18	dep	plasmids	1599:1606	arg1	plasmids					1599:1606	DNA plasmids	1595:1606	DNA plasmids (SYN Pfs48/45 and SYN Pfs25)	1595:1635	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	9	18	dep	plasmids	1599:1606	arg1	Pfs48/45					1613:1620	SYN Pfs48/45	1609:1620	SYN Pfs48/45	1609:1620	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	9	18	dep	plasmids	1599:1606	arg1	Pfs25					1630:1634	SYN Pfs25	1626:1634	SYN Pfs25	1626:1634	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	2	19	theme	Pfs48/45	289:296	arg1	Expression					275:284	Expression	275:284	Expression of Pfs48/45 in the erythrocytic sexual stages	275:330	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	2	19	theme	Pfs48/45	289:296	arg1	presentation					336:347	presentation	336:347	presentation to the immune system	336:368	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	6	20	theme	blocking	1031:1038	arg1	activity					1040:1047	transmission blocking activity	1018:1047	transmission blocking activity	1018:1047	EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine.
27912985	6	21	with	immunization	1061:1072	arg1	vaccine					1096:1102	SYN Pfs48/45 DNA vaccine	1079:1102	SYN Pfs48/45 DNA vaccine	1079:1102	EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine.
27912985	7	22	gly	N-glycosylation	1289:1303	arg2	sites					1305:1309	all N-glycosylation sites	1285:1309	all N-glycosylation sites mutated	1285:1317	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	5	23	link	-linked	884:890	arg1	glycosylation					892:904	any asparagine (N)-linked glycosylation	866:904	any asparagine (N)-linked glycosylation	866:904	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	3	24	dep	folded	499:504	arg1	active					520:525	active	520:525	active	520:525	However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms.
27912985	9	25	theme	life	1721:1724	arg1	stages					1732:1737	different life cycle stages	1711:1737	different life cycle stages	1711:1737	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	6	26	theme	transmission	1018:1029	arg1	activity					1040:1047	transmission blocking activity	1018:1047	transmission blocking activity	1018:1047	EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine.
27912985	7	27	theme	improved	1152:1159	arg1	immunogenicity					1172:1185	improved functional immunogenicity	1152:1185	improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact)	1152:1232	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	28	theme	feeding	1123:1129	arg1	assays					1131:1136	Mosquito membrane feeding assays	1105:1136	Mosquito membrane feeding assays	1105:1136	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	8	29	theme	response	1468:1475	arg1	boosting					1447:1454	significant boosting	1435:1454	significant boosting of antibody response	1435:1475	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	7	30	gly	N-glycosylation	1204:1218	arg2	sites					1220:1224	N-glycosylation sites intact	1204:1231	N-glycosylation sites intact	1204:1231	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	30	gly	N-glycosylation	1204:1218	arg2	Pfs48/45					1194:1201	SYN Pfs48/45	1190:1201	SYN Pfs48/45 (N-glycosylation sites intact)	1190:1232	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	31	theme	Pfs48/45	1262:1269	arg1	plasmids					1275:1282	MUT2 Pfs48/45 DNA plasmids	1257:1282	MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated)	1257:1318	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	2	32	theme	human	394:398	arg1	host					400:403	the human host	390:403	the human host	390:403	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	9	33	with	immunization	1560:1571	arg1	combination					1580:1590	a combination	1578:1590	a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25)	1578:1635	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	8	34	theme	vaccines	1541:1548	arg1	capabilities					1512:1523	transmission reducing capabilities	1490:1523	transmission reducing capabilities of all four DNA vaccines	1490:1548	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	3	35	theme	protein	551:557	arg1	platforms					570:578	various protein expression platforms	543:578	various protein expression platforms	543:578	However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms.
27912985	8	36	theme	transmission	1490:1501	arg1	capabilities					1512:1523	transmission reducing capabilities	1490:1523	transmission reducing capabilities of all four DNA vaccines	1490:1548	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	2	37	theme	natural	429:435	arg1	boosting					437:444	natural boosting	429:444	natural boosting	429:444	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	0	38	theme	malaria	19:25	arg1	transmission					27:38	malaria transmission	19:38	malaria transmission	19:38	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	0	39	theme	intramuscular	119:131	arg1	electroporation					133:147	intramuscular electroporation	119:147	intramuscular electroporation	119:147	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	2	40	theme	sexual	318:323	arg1	stages					325:330	the erythrocytic sexual stages	301:330	the erythrocytic sexual stages	301:330	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	1	41	theme	Plasmodium	215:224	arg1	falciparum					226:235	Plasmodium falciparum transmission blocking vaccines (TBV)	215:272	Plasmodium falciparum transmission blocking vaccines (TBV)	215:272	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	7	42	theme	membrane	1114:1121	arg1	assays					1131:1136	Mosquito membrane feeding assays	1105:1136	Mosquito membrane feeding assays	1105:1136	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	4	43	theme	immune	713:718	arg1	responses					720:728	significant transmission reducing immune responses	679:728	significant transmission reducing immune responses	679:728	In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses.
27912985	8	44	with	immunization	1370:1381	arg1	each					1388:1391	each	1388:1391	each	1388:1391	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	8	44	with	immunization	1370:1381	arg1	vaccines					1414:1421	the different DNA vaccines	1396:1421	the different DNA vaccines	1396:1421	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	4	45	theme	DNA	648:650	arg1	plasmids					652:659	DNA plasmids	648:659	DNA plasmids	648:659	In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses.
27912985	2	46	from	Expression	275:284	arg1	stages					325:330	the erythrocytic sexual stages	301:330	the erythrocytic sexual stages	301:330	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	2	46	from	Expression	275:284	arg1	host					400:403	the human host	390:403	the human host	390:403	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	1	47	theme	falciparum	226:235	arg1	development					200:210	the development	196:210	the development of Plasmodium falciparum transmission blocking vaccines (TBV)	196:272	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	0	48	theme	reducing	40:47	arg1	potency					49:55	reducing potency	40:55	reducing potency	40:55	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	5	49	theme	DNA	731:733	arg1	plasmids					735:742	DNA plasmids	731:742	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation	731:904	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	9	50	theme	DNA	1595:1597	arg1	plasmids					1599:1606	DNA plasmids	1595:1606	DNA plasmids (SYN Pfs48/45 and SYN Pfs25)	1595:1635	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	9	50	theme	DNA	1595:1597	arg1	Pfs48/45					1613:1620	SYN Pfs48/45	1609:1620	SYN Pfs48/45	1609:1620	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	9	50	theme	DNA	1595:1597	arg1	Pfs25					1630:1634	SYN Pfs25	1626:1634	SYN Pfs25	1626:1634	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	1	51	theme	transmission	237:248	arg1	TBV					269:271	TBV	269:271	TBV	269:271	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	1	51	theme	transmission	237:248	arg1	vaccines					259:266	transmission blocking vaccines	237:266	Plasmodium falciparum transmission blocking vaccines (TBV)	215:272	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	0	52	theme	Pfs48/45	60:67	arg1	Immunogenicity					0:13	Immunogenicity	0:13	Immunogenicity	0:13	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	0	52	theme	Pfs48/45	60:67	arg1	transmission					27:38	malaria transmission	19:38	malaria transmission	19:38	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	8	53	theme	Pfs48/45	1347:1354	arg1	protein					1356:1362	recombinant Pfs48/45 protein	1335:1362	recombinant Pfs48/45 protein	1335:1362	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	8	54	theme	significant	1435:1445	arg1	boosting					1447:1454	significant boosting	1435:1454	significant boosting of antibody response	1435:1475	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	5	55	dep	mutated	830:836	arg1	MUT2					848:851	MUT2	848:851	MUT2	848:851	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	5	55	dep	mutated	830:836	arg1	MUT1					839:842	MUT1	839:842	MUT1	839:842	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	8	56	theme	recombinant	1335:1345	arg1	protein					1356:1362	recombinant Pfs48/45 protein	1335:1362	recombinant Pfs48/45 protein	1335:1362	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	5	57	theme	optimized	790:798	arg1	codon					784:788	codon optimized	784:798	codon optimized (SYN)	784:804	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	5	57	theme	optimized	790:798	arg1	SYN					801:803	SYN	801:803	SYN	801:803	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	5	57	theme	optimized	790:798	arg1	native					771:776	native	771:776	native	771:776	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	7	58	theme	N-glycosylation	1204:1218	arg1	Pfs48/45					1194:1201	SYN Pfs48/45	1190:1201	SYN Pfs48/45 (N-glycosylation sites intact)	1190:1232	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	58	theme	N-glycosylation	1204:1218	arg1	sites					1220:1224	N-glycosylation sites intact	1204:1231	N-glycosylation sites intact	1204:1231	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	8	59	theme	antibody	1459:1466	arg1	response					1468:1475	antibody response	1459:1475	antibody response	1459:1475	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	2	60	theme	immune	356:361	arg1	system					363:368	the immune system	352:368	the immune system	352:368	Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting.
27912985	5	61	dep	native	771:776	arg1	optimized					816:824	optimized	816:824	optimized	816:824	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	5	61	dep	native	771:776	arg1	mutated					830:836	mutated	830:836	mutated	830:836	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	5	61	dep	native	771:776	arg1	WT					779:780	WT	779:780	WT	779:780	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	8	62	theme	DNA	1410:1412	arg1	vaccines					1414:1421	the different DNA vaccines	1396:1421	the different DNA vaccines	1396:1421	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	9	63	theme	cycle	1726:1730	arg1	stages					1732:1737	different life cycle stages	1711:1737	different life cycle stages	1711:1737	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	8	64	theme	different	1400:1408	arg1	vaccines					1414:1421	the different DNA vaccines	1396:1421	the different DNA vaccines	1396:1421	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	1	65	dep	falciparum	226:235	arg1	TBV					269:271	TBV	269:271	TBV	269:271	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	1	65	dep	falciparum	226:235	arg1	vaccines					259:266	transmission blocking vaccines	237:266	Plasmodium falciparum transmission blocking vaccines (TBV)	215:272	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	9	66	theme	SYN	1626:1628	arg1	plasmids					1599:1606	DNA plasmids	1595:1606	DNA plasmids (SYN Pfs48/45 and SYN Pfs25)	1595:1635	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	9	66	theme	SYN	1626:1628	arg1	Pfs25					1630:1634	SYN Pfs25	1626:1634	SYN Pfs25	1626:1634	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	6	67	theme	Pfs48/45	1083:1090	arg1	vaccine					1096:1102	SYN Pfs48/45 DNA vaccine	1079:1102	SYN Pfs48/45 DNA vaccine	1079:1102	EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine.
27912985	5	68	theme	-linked	884:890	arg1	glycosylation					892:904	any asparagine (N)-linked glycosylation	866:904	any asparagine (N)-linked glycosylation	866:904	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	1	69	theme	blocking	250:257	arg1	TBV					269:271	TBV	269:271	TBV	269:271	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	1	69	theme	blocking	250:257	arg1	vaccines					259:266	transmission blocking vaccines	237:266	Plasmodium falciparum transmission blocking vaccines (TBV)	215:272	Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV).
27912985	7	70	theme	MUT2	1257:1260	arg1	plasmids					1275:1282	MUT2 Pfs48/45 DNA plasmids	1257:1282	MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated)	1257:1318	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	5	71	theme	intramuscular	936:948	arg1	electroporation					950:964	intramuscular electroporation	936:964	intramuscular electroporation (EP)	936:969	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	5	71	theme	intramuscular	936:948	arg1	EP					967:968	EP	967:968	EP	967:968	DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP).
27912985	6	72	theme	SYN	1079:1081	arg1	vaccine					1096:1102	SYN Pfs48/45 DNA vaccine	1079:1102	SYN Pfs48/45 DNA vaccine	1079:1102	EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine.
27912985	8	73	with	Boosting	1321:1328	arg1	protein					1356:1362	recombinant Pfs48/45 protein	1335:1362	recombinant Pfs48/45 protein	1335:1362	Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines.
27912985	0	74	theme	Pfs25	73:77	arg1	Immunogenicity					0:13	Immunogenicity	0:13	Immunogenicity	0:13	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	0	74	theme	Pfs25	73:77	arg1	transmission					27:38	malaria transmission	19:38	malaria transmission	19:38	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	7	75	theme	DNA	1271:1273	arg1	plasmids					1275:1282	MUT2 Pfs48/45 DNA plasmids	1257:1282	MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated)	1257:1318	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	76	dep	plasmids	1275:1282	arg1	sites					1305:1309	all N-glycosylation sites	1285:1309	all N-glycosylation sites mutated	1285:1317	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	9	77	theme	SYN	1609:1611	arg1	plasmids					1599:1606	DNA plasmids	1595:1606	DNA plasmids (SYN Pfs48/45 and SYN Pfs25)	1595:1635	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	9	77	theme	SYN	1609:1611	arg1	Pfs48/45					1613:1620	SYN Pfs48/45	1609:1620	SYN Pfs48/45	1609:1620	Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.
27912985	4	78	theme	significant	679:689	arg1	responses					720:728	significant transmission reducing immune responses	679:728	significant transmission reducing immune responses	679:728	In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses.
27912985	4	79	theme	full-length	616:626	arg1	Pfs48/45					628:635	full-length Pfs48/45	616:635	full-length Pfs48/45 encoded by DNA plasmids	616:659	In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses.
27912985	7	80	theme	functional	1161:1170	arg1	immunogenicity					1172:1185	improved functional immunogenicity	1152:1185	improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact)	1152:1232	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	0	81	dep	Immunogenicity	0:13	arg1	potency					49:55	reducing potency	40:55	reducing potency	40:55	Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation.
27912985	7	82	theme	intact	1226:1231	arg1	Pfs48/45					1194:1201	SYN Pfs48/45	1190:1201	SYN Pfs48/45 (N-glycosylation sites intact)	1190:1232	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	82	theme	intact	1226:1231	arg1	sites					1220:1224	N-glycosylation sites intact	1204:1231	N-glycosylation sites intact	1204:1231	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	83	theme	SYN	1190:1192	arg1	Pfs48/45					1194:1201	SYN Pfs48/45	1190:1201	SYN Pfs48/45 (N-glycosylation sites intact)	1190:1232	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
27912985	7	83	theme	SYN	1190:1192	arg1	sites					1220:1224	N-glycosylation sites intact	1204:1231	N-glycosylation sites intact	1204:1231	Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated).
30044221	6	0	theme	rational	1194:1201	arg1	design					1203:1208	rational design	1194:1208	rational design of novel therapeutic agents	1194:1236	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	4	1	theme	Å	820:820	arg1	resolution					822:831	3.1-3.8 Å resolution	812:831	3.1-3.8 Å resolution	812:831	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	6	2	theme	structural	1124:1133	arg1	studies					1135:1141	structural studies	1124:1141	structural studies of heteromeric GABAA receptors	1124:1172	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	3	3	theme	heteromeric	557:567	arg1	receptors					575:583	heteromeric GABAA receptors	557:583	heteromeric GABAA receptors	557:583	Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination.
30044221	1	4	theme	Cys-loop	277:284	arg1	receptors					286:294	pentameric Cys-loop receptors	266:294	pentameric Cys-loop receptors	266:294	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	0	5	from	structure	8:16	arg1	complex					92:98	complex	92:98	complex with GABA	92:108	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	3	6	theme	GABAA	569:573	arg1	receptors					575:583	heteromeric GABAA receptors	557:583	heteromeric GABAA receptors	557:583	Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination.
30044221	1	7	theme	receptors	286:294	arg1	superfamily					251:261	the superfamily	247:261	the superfamily of pentameric Cys-loop receptors	247:294	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	0	8	with	complex	92:98	arg1	GABA					105:108	GABA	105:108	GABA	105:108	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	2	9	theme	heteromeric	324:334	arg1	receptors					310:318	Native GABAA receptors	297:318	Native GABAA receptors	297:318	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	2	9	theme	heteromeric	324:334	arg1	assemblies					336:345	heteromeric assemblies	324:345	heteromeric assemblies sensitive to many important drugs	324:379	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	6	10	theme	therapeutic	1219:1229	arg1	agents					1231:1236	novel therapeutic agents	1213:1236	novel therapeutic agents	1213:1236	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	5	11	link	N-linked	920:927	arg1	glycosylation					929:941	Remarkable N-linked glycosylation	909:941	Remarkable N-linked glycosylation on the α1 subunit	909:959	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	2	12	theme	important	365:373	arg1	drugs					375:379	many important drugs	360:379	many important drugs	360:379	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	5	13	theme	N-linked	920:927	arg1	glycosylation					929:941	Remarkable N-linked glycosylation	909:941	Remarkable N-linked glycosylation on the α1 subunit	909:959	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	4	14	theme	molecular	846:854	arg1	principles					856:865	molecular principles	846:865	molecular principles of receptor assembly and agonist binding	846:906	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	5	15	gly	glycosylation	929:941	arg1	subunit					953:959	the α1 subunit	946:959	the α1 subunit	946:959	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	4	16	theme	GABAA	734:738	arg1	receptor					740:747	a tri-heteromeric α1β1γ2SEM GABAA receptor	706:747	a tri-heteromeric α1β1γ2SEM GABAA receptor	706:747	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	2	17	theme	neurological	499:510	arg1	diseases					512:519	multiple neurological diseases	490:519	multiple neurological diseases	490:519	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	6	18	theme	agents	1231:1236	arg1	design					1203:1208	rational design	1194:1208	rational design of novel therapeutic agents	1194:1236	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	2	19	theme	GABAA	304:308	arg1	receptors					310:318	Native GABAA receptors	297:318	Native GABAA receptors	297:318	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	2	19	theme	GABAA	304:308	arg1	assemblies					336:345	heteromeric assemblies	324:345	heteromeric assemblies sensitive to many important drugs	324:379	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	4	20	theme	α1β1γ2SEM	724:732	arg1	receptor					740:747	a tri-heteromeric α1β1γ2SEM GABAA receptor	706:747	a tri-heteromeric α1β1γ2SEM GABAA receptor	706:747	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	2	21	theme	multiple	490:497	arg1	diseases					512:519	multiple neurological diseases	490:519	multiple neurological diseases	490:519	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	4	22	with	complex	752:758	arg1	GABA					765:768	GABA	765:768	GABA	765:768	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	6	23	theme	receptors	1164:1172	arg1	studies					1135:1141	structural studies	1124:1141	structural studies of heteromeric GABAA receptors	1124:1172	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	2	24	from	sedatives	387:395	arg1	receptors					310:318	Native GABAA receptors	297:318	Native GABAA receptors	297:318	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	2	24	from	sedatives	387:395	arg1	assemblies					336:345	heteromeric assemblies	324:345	heteromeric assemblies sensitive to many important drugs	324:379	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	2	25	theme	many	360:363	arg1	drugs					375:379	many important drugs	360:379	many important drugs	360:379	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	3	26	theme	receptors	575:583	arg1	importance					543:552	the profound importance	530:552	the profound importance of heteromeric GABAA receptors in neuroscience and medicine	530:612	Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination.
30044221	1	27	theme	GABAA	200:204	arg1	receptors					206:214	GABAA receptors	200:214	GABAA receptors	200:214	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	1	27	theme	GABAA	200:204	arg1	members					236:242	chloride-selective members	217:242	chloride-selective members of the superfamily of pentameric Cys-loop receptors	217:294	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	0	28	theme	Cryo-EM	0:6	arg1	structure					8:16	Cryo-EM structure	0:16	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.	0:109	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	4	29	theme	single	785:790	arg1	cryo-EM					801:807	single particle cryo-EM	785:807	single particle cryo-EM	785:807	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	1	30	from	neurotransmission	127:143	arg1	system					170:175	the mammalian nervous system	148:175	the mammalian nervous system	148:175	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	2	31	theme	anticonvulsant	416:429	arg1	agents					431:436	anticonvulsant agents	416:436	anticonvulsant agents	416:436	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	3	32	from	importance	543:552	arg1	medicine					605:612	medicine	605:612	medicine	605:612	Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination.
30044221	3	32	from	importance	543:552	arg1	neuroscience					588:599	neuroscience	588:599	neuroscience	588:599	Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination.
30044221	4	33	theme	binding	900:906	arg1	principles					856:865	molecular principles	846:865	molecular principles of receptor assembly and agonist binding	846:906	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	1	34	theme	Fast	111:114	arg1	neurotransmission					127:143	Fast inhibitory neurotransmission	111:143	Fast inhibitory neurotransmission in the mammalian nervous system	111:175	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	6	35	theme	GABAA	1158:1162	arg1	receptors					1164:1172	heteromeric GABAA receptors	1146:1172	heteromeric GABAA receptors	1146:1172	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	2	36	theme	GABAA	460:464	arg1	receptors					466:474	GABAA receptors	460:474	GABAA receptors implicated in multiple neurological diseases	460:519	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	2	37	theme	receptors	466:474	arg1	forms					451:455	mutant forms	444:455	mutant forms of GABAA receptors implicated in multiple neurological diseases	444:519	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	1	38	theme	inhibitory	116:125	arg1	neurotransmission					127:143	Fast inhibitory neurotransmission	111:143	Fast inhibitory neurotransmission in the mammalian nervous system	111:175	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	1	39	theme	chloride-selective	217:234	arg1	receptors					206:214	GABAA receptors	200:214	GABAA receptors	200:214	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	1	39	theme	chloride-selective	217:234	arg1	members					236:242	chloride-selective members	217:242	chloride-selective members of the superfamily of pentameric Cys-loop receptors	217:294	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	0	40	theme	α1β1γ2S	50:56	arg1	receptor					80:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	5	41	theme	receptor	1043:1050	arg1	assembly					1052:1059	receptor assembly	1043:1059	receptor assembly	1043:1059	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	4	42	theme	agonist	892:898	arg1	binding					900:906	agonist binding	892:906	agonist binding	892:906	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	4	43	theme	receptor	740:747	arg1	structure					693:701	the structure	689:701	the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA	689:768	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	4	44	theme	tri-heteromeric	708:722	arg1	receptor					740:747	a tri-heteromeric α1β1γ2SEM GABAA receptor	706:747	a tri-heteromeric α1β1γ2SEM GABAA receptor	706:747	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	0	45	theme	benzodiazepine-sensitive	25:48	arg1	receptor					80:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	2	46	with	assemblies	336:345	arg1	forms					451:455	mutant forms	444:455	mutant forms of GABAA receptors implicated in multiple neurological diseases	444:519	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	5	47	from	glycosylation	929:941	arg1	subunit					953:959	the α1 subunit	946:959	the α1 subunit	946:959	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	2	48	theme	mutant	444:449	arg1	forms					451:455	mutant forms	444:455	mutant forms of GABAA receptors implicated in multiple neurological diseases	444:519	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	0	49	theme	GABAA	74:78	arg1	receptor					80:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	6	50	theme	novel	1213:1217	arg1	agents					1231:1236	novel therapeutic agents	1213:1236	novel therapeutic agents	1213:1236	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	0	51	theme	tri-heteromeric	58:72	arg1	receptor					80:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor	21:87	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	3	52	theme	structure	648:656	arg1	determination					658:670	structure determination	648:670	structure determination	648:670	Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination.
30044221	5	53	theme	ion	1005:1007	arg1	channel					1009:1015	the ion channel	1001:1015	the ion channel	1001:1015	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	5	54	theme	ion	1073:1075	arg1	gating					1085:1090	ion channel gating	1073:1090	ion channel gating	1073:1090	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	2	55	theme	Native	297:302	arg1	receptors					310:318	Native GABAA receptors	297:318	Native GABAA receptors	297:318	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	2	55	theme	Native	297:302	arg1	assemblies					336:345	heteromeric assemblies	324:345	heteromeric assemblies sensitive to many important drugs	324:379	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	4	56	theme	particle	792:799	arg1	cryo-EM					801:807	single particle cryo-EM	785:807	single particle cryo-EM	785:807	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	2	57	theme	sensitive	347:355	arg1	receptors					310:318	Native GABAA receptors	297:318	Native GABAA receptors	297:318	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	2	57	theme	sensitive	347:355	arg1	assemblies					336:345	heteromeric assemblies	324:345	heteromeric assemblies sensitive to many important drugs	324:379	Native GABAA receptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsant agents, with mutant forms of GABAA receptors implicated in multiple neurological diseases.
30044221	6	58	theme	heteromeric	1146:1156	arg1	receptors					1164:1172	heteromeric GABAA receptors	1146:1172	heteromeric GABAA receptors	1146:1172	Our work provides a pathway to structural studies of heteromeric GABAA receptors and a framework for rational design of novel therapeutic agents.
30044221	5	59	theme	channel	1009:1015	arg1	vestibule					988:996	the extracellular vestibule	970:996	the extracellular vestibule of the ion channel	970:1015	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	5	60	theme	channel	1077:1083	arg1	gating					1085:1090	ion channel gating	1073:1090	ion channel gating	1073:1090	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	1	61	theme	mammalian	152:160	arg1	system					170:175	the mammalian nervous system	148:175	the mammalian nervous system	148:175	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	1	62	theme	superfamily	251:261	arg1	receptors					206:214	GABAA receptors	200:214	GABAA receptors	200:214	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	1	62	theme	superfamily	251:261	arg1	members					236:242	chloride-selective members	217:242	chloride-selective members of the superfamily of pentameric Cys-loop receptors	217:294	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	4	63	theme	assembly	879:886	arg1	principles					856:865	molecular principles	846:865	molecular principles of receptor assembly and agonist binding	846:906	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	5	64	theme	Remarkable	909:918	arg1	glycosylation					929:941	Remarkable N-linked glycosylation	909:941	Remarkable N-linked glycosylation on the α1 subunit	909:959	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	1	65	theme	nervous	162:168	arg1	system					170:175	the mammalian nervous system	148:175	the mammalian nervous system	148:175	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
30044221	3	66	theme	profound	534:541	arg1	importance					543:552	the profound importance	530:552	the profound importance of heteromeric GABAA receptors in neuroscience and medicine	530:612	Despite the profound importance of heteromeric GABAA receptors in neuroscience and medicine, they have proven recalcitrant to structure determination.
30044221	0	67	theme	receptor	80:87	arg1	structure					8:16	Cryo-EM structure	0:16	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.	0:109	Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
30044221	4	68	from	structure	693:701	arg1	complex					752:758	complex	752:758	complex with GABA	752:768	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	4	69	theme	receptor	870:877	arg1	assembly					879:886	receptor assembly	870:886	receptor assembly	870:886	Here we present the structure of a tri-heteromeric α1β1γ2SEM GABAA receptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating molecular principles of receptor assembly and agonist binding.
30044221	5	70	theme	extracellular	974:986	arg1	vestibule					988:996	the extracellular vestibule	970:996	the extracellular vestibule of the ion channel	970:1015	Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating.
30044221	1	71	theme	pentameric	266:275	arg1	receptors					286:294	pentameric Cys-loop receptors	266:294	pentameric Cys-loop receptors	266:294	Fast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAA receptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors.
29562282	10	0	theme	diverse	1576:1582	arg1	progresses					1593:1602	diverse cellular progresses	1576:1602	diverse cellular progresses	1576:1602	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	12	1	theme	useful	1840:1845	arg1	tool					1847:1850	a new useful tool	1834:1850	a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides	1834:1924	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	12	1	theme	useful	1840:1845	arg1	lectin					1824:1829	the AANL lectin	1815:1829	the AANL lectin	1815:1829	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	9	2	from	samples	1371:1377	arg1	peak					1354:1357	the late flow-through peak	1332:1357	the late flow-through peak from simple samples	1332:1377	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	9	3	theme	Sepharose	1405:1413	arg1	4B-AANL					1415:1421	Sepharose 4B-AANL	1405:1421	Sepharose 4B-AANL	1405:1421	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	9	3	theme	Sepharose	1405:1413	arg1	columns					1397:1403	affinity columns Sepharose 4B-AANL or POROS-AANL	1388:1435	affinity columns Sepharose 4B-AANL or POROS-AANL	1388:1435	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	10	4	theme	cellular	1584:1591	arg1	progresses					1593:1602	diverse cellular progresses	1576:1602	diverse cellular progresses	1576:1602	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	2	5	theme	polypeptide	372:382	arg1	chains					384:389	nascent polypeptide chains	364:389	nascent polypeptide chains	364:389	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	6	6	theme	binding	1044:1050	arg1	selectivity					1052:1062	high binding selectivity	1039:1062	high binding selectivity for terminal N-acetylglucosamine	1039:1095	A novel lectin from Agrocybe aegerita shows high binding selectivity for terminal N-acetylglucosamine.
29562282	1	7	theme	post-translational	148:165	arg1	modification					167:178	an important post-translational modification	135:178	an important post-translational modification	135:178	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	7	theme	post-translational	148:165	arg1	N-acetylglucosamine					94:112	O-linked N-acetylglucosamine	85:112	O-linked N-acetylglucosamine (O-GlcNAcylation)	85:130	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	10	8	theme	urea	1651:1654	arg1	cycle					1656:1660	urea cycle	1651:1660	urea cycle	1651:1660	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	5	9	theme	array	677:681	arg1	analyses					683:690	Glycan array analyses	670:690	Glycan array analyses	670:690	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	10	theme	Pan	939:941	arg1	Y					943:943	Pan Y	939:943	Pan Y	939:943	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	10	theme	Pan	939:941	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	2	11	theme	cell	288:291	arg1	chains					384:389	nascent polypeptide chains	364:389	nascent polypeptide chains	364:389	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	11	theme	cell	288:291	arg1	processes					293:301	many cell processes	283:301	many cell processes	283:301	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	11	theme	cell	288:291	arg1	transcription					314:326	transcription	314:326	transcription	314:326	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	11	theme	cell	288:291	arg1	cycle					334:338	cell cycle	329:338	cell cycle	329:338	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	11	theme	cell	288:291	arg1	development					348:358	neural development	341:358	neural development	341:358	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	10	12	theme	AANL	1455:1458	arg1	column					1469:1474	AANL affinity column	1455:1474	AANL affinity column	1455:1474	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	1	13	theme	O-linked	85:92	arg1	N-acetylglucosamine					94:112	O-linked N-acetylglucosamine	85:112	O-linked N-acetylglucosamine (O-GlcNAcylation)	85:130	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	13	theme	O-linked	85:92	arg1	modification					167:178	an important post-translational modification	135:178	an important post-translational modification	135:178	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	13	theme	O-linked	85:92	arg1	O-GlcNAcylation					115:129	O-GlcNAcylation	115:129	O-GlcNAcylation	115:129	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	6	14	theme	novel	997:1001	arg1	lectin					1003:1008	A novel lectin	995:1008	A novel lectin from Agrocybe aegerita	995:1031	A novel lectin from Agrocybe aegerita shows high binding selectivity for terminal N-acetylglucosamine.
29562282	10	15	theme	hydrolysis	1630:1639	arg1	progress					1641:1648	hydrolysis progress	1630:1648	hydrolysis progress	1630:1648	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	1	16	from	modification	167:178	arg1	threonine					193:201	threonine	193:201	threonine	193:201	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	16	from	modification	167:178	arg1	serine					183:188	serine	183:188	serine	183:188	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	9	17	theme	flow-through	1341:1352	arg1	peak					1354:1357	the late flow-through peak	1332:1357	the late flow-through peak from simple samples	1332:1377	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	12	18	theme	proteins	1904:1911	arg1	identification					1871:1884	identification	1871:1884	identification	1871:1884	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	12	18	theme	proteins	1904:1911	arg1	enrichment					1856:1865	enrichment	1856:1865	enrichment	1856:1865	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	10	19	theme	cell	1686:1689	arg1	cycle					1691:1695	cell cycle	1686:1695	cell cycle	1686:1695	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	5	20	with	consistent	821:830	arg1	result					841:846	the result	837:846	the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y	837:921	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	20	with	consistent	821:830	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	12	21	theme	peptides	1917:1924	arg1	identification					1871:1884	identification	1871:1884	identification	1871:1884	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	12	21	theme	peptides	1917:1924	arg1	enrichment					1856:1865	enrichment	1856:1865	enrichment	1856:1865	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	0	22	theme	facile	43:48	arg1	AANL					0:3	AANL	0:3	AANL (Agrocybe aegerita lectin 2)	0:32	AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.
29562282	0	22	theme	facile	43:48	arg1	tool					50:53	a new facile tool	37:53	a new facile tool to probe for O-GlcNAcylation	37:82	AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.
29562282	5	23	theme	plasmon	704:710	arg1	resonance					712:720	surface plasmon resonance	696:720	surface plasmon resonance (SPR) assays	696:733	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	23	theme	plasmon	704:710	arg1	SPR					723:725	SPR	723:725	SPR	723:725	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	24	dep	Liang	973:977	arg1	Y					979:979	Y	979:979	Wong BH, Liang Y	964:979	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	25	theme	Yu	952:953	arg1	G					955:955	Yu G	952:955	Yu G	952:955	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	25	theme	Yu	952:953	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	3	26	theme	facile	419:424	arg1	identification					426:439	the facile identification	415:439	the facile identification of O-GlcNAc	415:451	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
29562282	3	26	theme	facile	419:424	arg1	bottleneck					464:473	a major bottleneck	456:473	a major bottleneck in O-GlcNAcylation research	456:501	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
29562282	4	27	theme	Agrocybe	537:544	arg1	aegerita					546:553	Agrocybe aegerita	537:553	Agrocybe aegerita GlcNAc-specific lectin (AANL)	537:583	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	3	28	theme	major	458:462	arg1	identification					426:439	the facile identification	415:439	the facile identification of O-GlcNAc	415:451	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
29562282	3	28	theme	major	458:462	arg1	bottleneck					464:473	a major bottleneck	456:473	a major bottleneck in O-GlcNAcylation research	456:501	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
29562282	0	29	theme	Agrocybe	6:13	arg1	aegerita					15:22	Agrocybe aegerita	6:22	Agrocybe aegerita lectin 2	6:31	AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.
29562282	5	30	theme	et	982:983	arg1	2012					989:992	et al. 2012	982:992	et al. 2012	982:992	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	30	theme	et	982:983	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	8	31	theme	Confocal	1124:1131	arg1	imaging					1133:1139	Confocal imaging	1124:1139	Confocal imaging	1124:1139	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	4	32	theme	GlcNAc-specific	555:569	arg1	lectin					529:534	a lectin	527:534	a lectin	527:534	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	4	32	theme	GlcNAc-specific	555:569	arg1	AANL					579:582	AANL	579:582	AANL	579:582	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	4	32	theme	GlcNAc-specific	555:569	arg1	lectin					571:576	Agrocybe aegerita GlcNAc-specific lectin	537:576	Agrocybe aegerita GlcNAc-specific lectin (AANL)	537:583	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	10	33	theme	HexNAc-modified	1519:1533	arg1	peptides					1535:1542	28 high-confidence O-linked HexNAc-modified peptides	1491:1542	28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle	1491:1695	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	8	34	theme	O-GlcNAcylated	1204:1217	arg1	NUP62					1187:1191	NUP62	1187:1191	NUP62	1187:1191	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	8	34	theme	O-GlcNAcylated	1204:1217	arg1	glycoprotein					1245:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	11	35	theme	dbOGAP	1771:1776	arg1	database					1778:1785	the dbOGAP database	1767:1785	the dbOGAP database	1767:1785	And most importantly, major proteins and sites were not annotated in the dbOGAP database.
29562282	8	36	theme	abundant	1223:1230	arg1	NUP62					1187:1191	NUP62	1187:1191	NUP62	1187:1191	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	8	36	theme	abundant	1223:1230	arg1	glycoprotein					1245:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	10	37	link	O-linked	1510:1517	arg1	peptides					1535:1542	28 high-confidence O-linked HexNAc-modified peptides	1491:1542	28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle	1491:1695	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	8	38	theme	pore	1240:1243	arg1	NUP62					1187:1191	NUP62	1187:1191	NUP62	1187:1191	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	8	38	theme	pore	1240:1243	arg1	glycoprotein					1245:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	3	39	from	bottleneck	464:473	arg1	research					494:501	O-GlcNAcylation research	478:501	O-GlcNAcylation research	478:501	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
29562282	1	40	theme	proteins	206:213	arg1	threonine					193:201	threonine	193:201	threonine	193:201	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	40	theme	proteins	206:213	arg1	serine					183:188	serine	183:188	serine	183:188	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	5	41	theme	dissociation	773:784	arg1	KD					796:797	KD	796:797	KD	796:797	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	41	theme	dissociation	773:784	arg1	consistent					821:830	consistent	821:830	consistent	821:830	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	41	theme	dissociation	773:784	arg1	constant					786:793	a dissociation constant	771:793	a dissociation constant (KD)	771:798	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	0	42	dep	AANL	0:3	arg1	aegerita					15:22	Agrocybe aegerita	6:22	Agrocybe aegerita lectin 2	6:31	AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.
29562282	2	43	theme	neural	341:346	arg1	development					348:358	neural development	341:358	neural development	341:358	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	6	44	theme	terminal	1068:1075	arg1	N-acetylglucosamine					1077:1095	terminal N-acetylglucosamine	1068:1095	terminal N-acetylglucosamine	1068:1095	A novel lectin from Agrocybe aegerita shows high binding selectivity for terminal N-acetylglucosamine.
29562282	1	45	located	observed	223:230	arg1	nucleus					235:241	nucleus	235:241	nucleus	235:241	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	45	located	observed	223:230	arg1	cytoplasm					246:254	cytoplasm	246:254	cytoplasm	246:254	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	45	located	observed	223:230	arg2	N-acetylglucosamine					94:112	O-linked N-acetylglucosamine	85:112	O-linked N-acetylglucosamine (O-GlcNAcylation)	85:130	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	45	located	observed	223:230	arg2	modification					167:178	an important post-translational modification	135:178	an important post-translational modification	135:178	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	2	46	theme	many	283:286	arg1	chains					384:389	nascent polypeptide chains	364:389	nascent polypeptide chains	364:389	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	46	theme	many	283:286	arg1	processes					293:301	many cell processes	283:301	many cell processes	283:301	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	46	theme	many	283:286	arg1	transcription					314:326	transcription	314:326	transcription	314:326	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	46	theme	many	283:286	arg1	cycle					334:338	cell cycle	329:338	cell cycle	329:338	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	46	theme	many	283:286	arg1	development					348:358	neural development	341:358	neural development	341:358	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	8	47	gly	glycoprotein	1245:1256	arg1	NUP62					1187:1191	NUP62	1187:1191	NUP62	1187:1191	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	8	47	gly	glycoprotein	1245:1256	arg1	glycoprotein					1245:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	12	48	theme	new	1836:1838	arg1	tool					1847:1850	a new useful tool	1834:1850	a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides	1834:1924	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	12	48	theme	new	1836:1838	arg1	lectin					1824:1829	the AANL lectin	1815:1829	the AANL lectin	1815:1829	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	9	49	theme	O-GlcNAc-modified	1272:1288	arg1	peptides					1290:1297	O-GlcNAc-modified peptides	1272:1297	O-GlcNAc-modified peptides	1272:1297	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	1	50	theme	important	138:146	arg1	modification					167:178	an important post-translational modification	135:178	an important post-translational modification	135:178	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	50	theme	important	138:146	arg1	N-acetylglucosamine					94:112	O-linked N-acetylglucosamine	85:112	O-linked N-acetylglucosamine (O-GlcNAcylation)	85:130	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	6	51	theme	high	1039:1042	arg1	selectivity					1052:1062	high binding selectivity	1039:1062	high binding selectivity for terminal N-acetylglucosamine	1039:1095	A novel lectin from Agrocybe aegerita shows high binding selectivity for terminal N-acetylglucosamine.
29562282	5	52	theme	μM	808:809	arg1	KD					796:797	KD	796:797	KD	796:797	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	52	theme	μM	808:809	arg1	consistent					821:830	consistent	821:830	consistent	821:830	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	52	theme	μM	808:809	arg1	constant					786:793	a dissociation constant	771:793	a dissociation constant (KD)	771:798	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	12	53	theme	AANL	1819:1822	arg1	tool					1847:1850	a new useful tool	1834:1850	a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides	1834:1924	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	12	53	theme	AANL	1819:1822	arg1	lectin					1824:1829	the AANL lectin	1815:1829	the AANL lectin	1815:1829	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	4	54	theme	powerful	626:633	arg1	lectin					529:534	a lectin	527:534	a lectin	527:534	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	4	54	theme	powerful	626:633	arg1	probe					635:639	a powerful probe	624:639	a powerful probe for O-GlcNAc identification	624:667	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	5	55	theme	Glycan	670:675	arg1	analyses					683:690	Glycan array analyses	670:690	Glycan array analyses	670:690	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	56	dep	Chen	916:919	arg1	Y					921:921	Y	921:921	(Jiang S, Chen Y	906:921	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	11	57	theme	major	1720:1724	arg1	proteins					1726:1733	major proteins	1720:1733	major proteins	1720:1733	And most importantly, major proteins and sites were not annotated in the dbOGAP database.
29562282	6	58	theme	Agrocybe	1015:1022	arg1	aegerita					1024:1031	Agrocybe aegerita	1015:1031	Agrocybe aegerita	1015:1031	A novel lectin from Agrocybe aegerita shows high binding selectivity for terminal N-acetylglucosamine.
29562282	10	59	theme	affinity	1460:1467	arg1	column					1469:1474	AANL affinity column	1455:1474	AANL affinity column	1455:1474	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	5	60	theme	Gu	946:947	arg1	B					949:949	Gu B	946:949	Gu B	946:949	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	60	theme	Gu	946:947	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	10	61	theme	alcohol	1663:1669	arg1	metabolism					1671:1680	alcohol metabolism	1663:1680	alcohol metabolism	1663:1680	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	9	62	dep	columns	1397:1403	arg1	4B-AANL					1415:1421	Sepharose 4B-AANL	1405:1421	Sepharose 4B-AANL	1405:1421	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	9	62	dep	columns	1397:1403	arg1	columns					1397:1403	affinity columns Sepharose 4B-AANL or POROS-AANL	1388:1435	affinity columns Sepharose 4B-AANL or POROS-AANL	1388:1435	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	9	62	dep	columns	1397:1403	arg1	POROS-AANL					1426:1435	POROS-AANL	1426:1435	POROS-AANL	1426:1435	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	5	63	theme	Yin	932:934	arg1	Y					936:936	Yin Y	932:936	Yin Y	932:936	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	63	theme	Yin	932:934	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	9	64	theme	late	1336:1339	arg1	peak					1354:1357	the late flow-through peak	1332:1357	the late flow-through peak from simple samples	1332:1377	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	6	65	from	aegerita	1024:1031	arg1	lectin					1003:1008	A novel lectin	995:1008	A novel lectin from Agrocybe aegerita	995:1031	A novel lectin from Agrocybe aegerita shows high binding selectivity for terminal N-acetylglucosamine.
29562282	0	66	theme	new	39:41	arg1	AANL					0:3	AANL	0:3	AANL (Agrocybe aegerita lectin 2)	0:32	AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.
29562282	0	66	theme	new	39:41	arg1	tool					50:53	a new facile tool	37:53	a new facile tool to probe for O-GlcNAcylation	37:82	AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.
29562282	4	67	used	used	616:619	arg2	lectin					571:576	Agrocybe aegerita GlcNAc-specific lectin	537:576	Agrocybe aegerita GlcNAc-specific lectin (AANL)	537:583	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	4	67	used	used	616:619	arg2	probe					635:639	a powerful probe	624:639	a powerful probe for O-GlcNAc identification	624:667	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	4	67	used	used	616:619	arg2	lectin					529:534	a lectin	527:534	a lectin	527:534	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	12	68	theme	O-GlcNAcylated	1889:1902	arg1	proteins					1904:1911	O-GlcNAcylated proteins	1889:1911	O-GlcNAcylated proteins	1889:1911	These results suggest that the AANL lectin is a new useful tool for enrichment and identification of O-GlcNAcylated proteins and peptides.
29562282	5	69	theme	Li	958:959	arg1	Y					961:961	Li Y	958:961	Li Y	958:961	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	69	theme	Li	958:959	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	9	70	theme	simple	1364:1369	arg1	samples					1371:1377	simple samples	1364:1377	simple samples	1364:1377	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	5	71	theme	surface	696:702	arg1	resonance					712:720	surface plasmon resonance	696:720	surface plasmon resonance (SPR) assays	696:733	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	71	theme	surface	696:702	arg1	SPR					723:725	SPR	723:725	SPR	723:725	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	72	theme	resonance	712:720	arg1	assays					728:733	surface plasmon resonance (SPR) assays	696:733	surface plasmon resonance (SPR) assays	696:733	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	9	73	theme	affinity	1388:1395	arg1	4B-AANL					1415:1421	Sepharose 4B-AANL	1405:1421	Sepharose 4B-AANL	1405:1421	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	9	73	theme	affinity	1388:1395	arg1	columns					1397:1403	affinity columns Sepharose 4B-AANL or POROS-AANL	1388:1435	affinity columns Sepharose 4B-AANL or POROS-AANL	1388:1435	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	9	73	theme	affinity	1388:1395	arg1	POROS-AANL					1426:1435	POROS-AANL	1426:1435	POROS-AANL	1426:1435	Furthermore, O-GlcNAc-modified peptides could be effectively enriched in the late flow-through peak from simple samples by using affinity columns Sepharose 4B-AANL or POROS-AANL.
29562282	3	74	theme	O-GlcNAc	444:451	arg1	identification					426:439	the facile identification	415:439	the facile identification of O-GlcNAc	415:451	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
29562282	3	74	theme	O-GlcNAc	444:451	arg1	bottleneck					464:473	a major bottleneck	456:473	a major bottleneck in O-GlcNAcylation research	456:501	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
29562282	5	75	theme	isothiocyanate	863:876	arg1	assay					884:888	isothiocyanate (ITC) assay	863:888	isothiocyanate (ITC) assay reported before (Jiang S, Chen Y	863:921	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	4	76	theme	aegerita	546:553	arg1	lectin					529:534	a lectin	527:534	a lectin	527:534	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	4	76	theme	aegerita	546:553	arg1	AANL					579:582	AANL	579:582	AANL	579:582	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	4	76	theme	aegerita	546:553	arg1	lectin					571:576	Agrocybe aegerita GlcNAc-specific lectin	537:576	Agrocybe aegerita GlcNAc-specific lectin (AANL)	537:583	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	2	77	dep	transcription	314:326	arg1	stabilization					391:403	stabilization	391:403	stabilization	391:403	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	2	78	theme	nascent	364:370	arg1	chains					384:389	nascent polypeptide chains	364:389	nascent polypeptide chains	364:389	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	5	79	theme	al.	985:987	arg1	2012					989:992	et al. 2012	982:992	et al. 2012	982:992	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	79	theme	al.	985:987	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	4	80	theme	O-GlcNAc	645:652	arg1	identification					654:667	O-GlcNAc identification	645:667	O-GlcNAc identification	645:667	Herein, we report that a lectin, Agrocybe aegerita GlcNAc-specific lectin (AANL), also reported as AAL2, can be used as a powerful probe for O-GlcNAc identification.
29562282	10	81	theme	O-linked	1510:1517	arg1	peptides					1535:1542	28 high-confidence O-linked HexNAc-modified peptides	1491:1542	28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle	1491:1695	Therefore, using AANL affinity column, we identified 28 high-confidence O-linked HexNAc-modified peptides mapped on 17 proteins involving diverse cellular progresses, including transcription, hydrolysis progress, urea cycle, alcohol metabolism and cell cycle.
29562282	5	82	theme	Wang	924:927	arg1	result					841:846	the result	837:846	the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y	837:921	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	Y					961:961	Li Y	958:961	Li Y	958:961	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	Y					936:936	Yin Y	932:936	Yin Y	932:936	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	B					949:949	Gu B	946:949	Gu B	946:949	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	G					955:955	Yu G	952:955	Yu G	952:955	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	M					929:929	Wang M	924:929	Wang M	924:929	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	Y					943:943	Pan Y	939:943	Pan Y	939:943	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	2012					989:992	et al. 2012	982:992	et al. 2012	982:992	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	5	82	theme	Wang	924:927	arg1	Liang					973:977	Liang	973:977	Liang	973:977	Glycan array analyses and surface plasmon resonance (SPR) assays show that AANL binds to GlcNAc with a dissociation constant (KD) of 94.6 μM, which is consistent with the result tested through isothiocyanate (ITC) assay reported before (Jiang S, Chen Y, Wang M, Yin Y, Pan Y, Gu B, Yu G, Li Y, Wong BH, Liang Y, et al. 2012.
29562282	2	83	theme	cell	329:332	arg1	cycle					334:338	cell cycle	329:338	cell cycle	329:338	O-GlcNAcylation regulates many cell processes, including transcription, cell cycle, neural development and nascent polypeptide chains stabilization.
29562282	0	84	dep	aegerita	15:22	arg1	lectin					24:29	lectin 2	24:31	Agrocybe aegerita lectin 2	6:31	AANL (Agrocybe aegerita lectin 2) is a new facile tool to probe for O-GlcNAcylation.
29562282	1	85	link	O-linked	85:92	arg1	N-acetylglucosamine					94:112	O-linked N-acetylglucosamine	85:112	O-linked N-acetylglucosamine (O-GlcNAcylation)	85:130	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	85	link	O-linked	85:92	arg1	modification					167:178	an important post-translational modification	135:178	an important post-translational modification	135:178	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	1	85	link	O-linked	85:92	arg1	O-GlcNAcylation					115:129	O-GlcNAcylation	115:129	O-GlcNAcylation	115:129	O-linked N-acetylglucosamine (O-GlcNAcylation) is an important post-translational modification on serine or threonine of proteins, mainly observed in nucleus or cytoplasm.
29562282	8	86	theme	nuclear	1232:1238	arg1	NUP62					1187:1191	NUP62	1187:1191	NUP62	1187:1191	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	8	86	theme	nuclear	1232:1238	arg1	glycoprotein					1245:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein	1194:1256	Confocal imaging shows that AANL co-localizes extensively with NUP62, a heavily O-GlcNAcylated and abundant nuclear pore glycoprotein.
29562282	3	87	theme	O-GlcNAcylation	478:492	arg1	research					494:501	O-GlcNAcylation research	478:501	O-GlcNAcylation research	478:501	However, the facile identification of O-GlcNAc is a major bottleneck in O-GlcNAcylation research.
28970495	5	0	theme	CD22	765:768	arg1	site					770:773	the CD22 site	761:773	the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution	761:842	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	7	1	theme	inhibition	1379:1388	arg1	mechanism					1366:1374	the mechanism	1362:1374	the mechanism of inhibition of B-cell activation	1362:1409	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	6	2	from	design	1040:1045	arg1	dysfunction.The					1078:1092	B-cell dysfunction.The	1071:1092	B-cell dysfunction.The	1071:1092	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	5	3	from	role	869:872	arg1	engagement					918:927	antibody engagement	909:927	antibody engagement	909:927	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	6	4	theme	therapeutic	1132:1142	arg1	target					1144:1149	a therapeutic target	1130:1149	a therapeutic target for depleting dysregulated B cells	1130:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	6	4	theme	therapeutic	1132:1142	arg1	CD22					1122:1125	B-cell-specific co-receptor CD22	1094:1125	B-cell-specific co-receptor CD22	1094:1125	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	7	5	theme	crystal	1269:1275	arg1	structure					1277:1285	its crystal structure	1265:1285	its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation	1265:1409	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	3	6	theme	unique	470:475	arg1	mode					477:480	a unique mode	468:480	a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins	468:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	4	7	theme	CD22	557:560	arg1	ectodomain					562:571	The CD22 ectodomain	553:571	The CD22 ectodomain	553:571	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	3	8	theme	human	335:339	arg1	CD22					341:344	human CD22	335:344	human CD22	335:344	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	3	9	theme	sialic	504:509	arg1	lectins					544:550	sialic acid-binding immunoglobulin-type lectins	504:550	sialic acid-binding immunoglobulin-type lectins	504:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	4	10	theme	B	664:664	arg1	cells					666:670	B cells	664:670	B cells	664:670	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	6	11	theme	valuable	1017:1024	arg1	clues					1026:1030	valuable clues	1017:1030	valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells	1017:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	3	12	theme	CD22	341:344	arg1	structure					322:330	the crystal structure	310:330	the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins	310:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	6	13	dep	modulators	1057:1066	arg1	target					1144:1149	a therapeutic target	1130:1149	a therapeutic target for depleting dysregulated B cells	1130:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	6	13	dep	modulators	1057:1066	arg1	CD22					1122:1125	B-cell-specific co-receptor CD22	1094:1125	B-cell-specific co-receptor CD22	1094:1125	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	7	14	theme	bound	1296:1300	arg1	epratuzumab					1323:1333	the bound therapeutic antibody epratuzumab	1292:1333	the bound therapeutic antibody epratuzumab	1292:1333	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	3	15	theme	acid-binding	511:522	arg1	lectins					544:550	sialic acid-binding immunoglobulin-type lectins	504:550	sialic acid-binding immunoglobulin-type lectins	504:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	5	16	theme	critical	860:867	arg1	role					869:872	a critical role	858:872	a critical role for CD22 N-linked glycosylation in antibody engagement	858:927	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	4	17	theme	trans	687:691	arg1	ligands					693:699	trans ligands	687:699	trans ligands	687:699	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	6	18	theme	B-cell	1071:1076	arg1	dysfunction.The					1078:1092	B-cell dysfunction.The	1071:1092	B-cell dysfunction.The	1071:1092	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	2	19	theme	autoimmune	256:265	arg1	diseases					267:274	autoimmune diseases	256:274	autoimmune diseases	256:274	As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers.
28970495	7	20	theme	activation	1400:1409	arg1	inhibition					1379:1388	inhibition	1379:1388	inhibition of B-cell activation	1379:1409	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	3	21	theme	sialic	407:412	arg1	ligands					419:425	α2-6 sialic acid ligands	402:425	α2-6 sialic acid ligands	402:425	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	7	22	theme	CD22	1248:1251	arg1	CD22					1248:1251	CD22	1248:1251	CD22	1248:1251	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	7	22	theme	CD22	1248:1251	arg1	ectodomain					1234:1243	the ectodomain	1230:1243	the ectodomain of CD22	1230:1251	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	3	23	from	resolution	355:364	arg1	structure					322:330	the crystal structure	310:330	the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins	310:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	6	24	theme	dysregulated	1165:1176	arg1	cells					1180:1184	dysregulated B cells	1165:1184	dysregulated B cells	1165:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	7	25	with	structure	1277:1285	arg1	epratuzumab					1323:1333	the bound therapeutic antibody epratuzumab	1292:1333	the bound therapeutic antibody epratuzumab	1292:1333	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	3	26	theme	acid	414:417	arg1	ligands					419:425	α2-6 sialic acid ligands	402:425	α2-6 sialic acid ligands	402:425	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	5	27	theme	antibody	803:810	arg1	epratuzumab					812:822	the therapeutic antibody epratuzumab	787:822	the therapeutic antibody epratuzumab at 3.1 Å resolution	787:842	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	6	28	from	modulators	1057:1066	arg1	dysfunction.The					1078:1092	B-cell dysfunction.The	1071:1092	B-cell dysfunction.The	1071:1092	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	6	29	theme	co-receptor	1110:1120	arg1	target					1144:1149	a therapeutic target	1130:1149	a therapeutic target for depleting dysregulated B cells	1130:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	6	29	theme	co-receptor	1110:1120	arg1	CD22					1122:1125	B-cell-specific co-receptor CD22	1094:1125	B-cell-specific co-receptor CD22	1094:1125	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	0	30	theme	Molecular	0:8	arg1	basis					10:14	Molecular basis	0:14	Molecular basis of human CD22 function and therapeutic targeting	0:63	Molecular basis of human CD22 function and therapeutic targeting.
28970495	6	31	from	dysfunction.The	1078:1092	arg1	design					1040:1045	the design	1036:1045	the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells	1036:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	1	32	theme	baseline	83:90	arg1	level					92:96	a baseline level	81:96	a baseline level of B-cell inhibition	81:117	CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check.
28970495	4	33	from	formation	651:659	arg1	cells					666:670	B cells	664:670	B cells	664:670	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	3	34	theme	α2-6	402:405	arg1	ligands					419:425	α2-6 sialic acid ligands	402:425	α2-6 sialic acid ligands	402:425	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	0	35	theme	human	19:23	arg1	function					30:37	human CD22 function	19:37	human CD22 function	19:37	Molecular basis of human CD22 function and therapeutic targeting.
28970495	6	36	theme	B-cell	995:1000	arg1	inhibition					1002:1011	B-cell inhibition	995:1011	B-cell inhibition	995:1011	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	3	37	theme	immunoglobulin-type	524:542	arg1	lectins					544:550	sialic acid-binding immunoglobulin-type lectins	504:550	sialic acid-binding immunoglobulin-type lectins	504:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	4	38	theme	CD22	634:637	arg1	formation					651:659	concomitant CD22 nanocluster formation	622:659	concomitant CD22 nanocluster formation on B cells	622:670	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	3	39	theme	2.1 Å	349:353	arg1	resolution					355:364	2.1 Å resolution	349:364	2.1 Å resolution	349:364	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	3	40	theme	recognition	485:495	arg1	mode					477:480	a unique mode	468:480	a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins	468:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	2	41	theme	B-cell-restricted	159:175	arg1	CD22					186:189	CD22	186:189	CD22	186:189	As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers.
28970495	2	41	theme	B-cell-restricted	159:175	arg1	antigen					177:183	a B-cell-restricted antigen	157:183	a B-cell-restricted antigen	157:183	As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers.
28970495	2	42	theme	blood	280:284	arg1	cancers					286:292	blood cancers	280:292	blood cancers	280:292	As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers.
28970495	4	43	theme	concomitant	622:632	arg1	formation					651:659	concomitant CD22 nanocluster formation	622:659	concomitant CD22 nanocluster formation on B cells	622:670	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	0	44	theme	function	30:37	arg1	basis					10:14	Molecular basis	0:14	Molecular basis of human CD22 function and therapeutic targeting	0:63	Molecular basis of human CD22 function and therapeutic targeting.
28970495	6	45	theme	B	1178:1178	arg1	cells					1180:1184	dysregulated B cells	1165:1184	dysregulated B cells	1165:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	5	46	link	N-linked	883:890	arg1	glycosylation					892:904	CD22 N-linked glycosylation	878:904	CD22 N-linked glycosylation	878:904	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	7	47	theme	therapeutic	1302:1312	arg1	epratuzumab					1323:1333	the bound therapeutic antibody epratuzumab	1292:1333	the bound therapeutic antibody epratuzumab	1292:1333	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	5	48	theme	CD22	878:881	arg1	glycosylation					892:904	CD22 N-linked glycosylation	878:904	CD22 N-linked glycosylation	878:904	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	0	49	theme	CD22	25:28	arg1	function					30:37	human CD22 function	19:37	human CD22 function	19:37	Molecular basis of human CD22 function and therapeutic targeting.
28970495	4	50	theme	nanocluster	639:649	arg1	formation					651:659	concomitant CD22 nanocluster formation	622:659	concomitant CD22 nanocluster formation on B cells	622:670	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	0	51	theme	therapeutic	43:53	arg1	targeting					55:63	therapeutic targeting	43:63	therapeutic targeting	43:63	Molecular basis of human CD22 function and therapeutic targeting.
28970495	5	52	theme	N-linked	883:890	arg1	glycosylation					892:904	CD22 N-linked glycosylation	878:904	CD22 N-linked glycosylation	878:904	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	6	53	theme	modulators	1057:1066	arg1	design					1040:1045	the design	1036:1045	the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells	1036:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	0	54	theme	targeting	55:63	arg1	basis					10:14	Molecular basis	0:14	Molecular basis of human CD22 function and therapeutic targeting	0:63	Molecular basis of human CD22 function and therapeutic targeting.
28970495	1	55	theme	B-cell	101:106	arg1	inhibition					108:117	B-cell inhibition	101:117	B-cell inhibition	101:117	CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check.
28970495	5	56	theme	therapeutic	791:801	arg1	epratuzumab					812:822	the therapeutic antibody epratuzumab	787:822	the therapeutic antibody epratuzumab at 3.1 Å resolution	787:842	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	6	57	theme	molecular	950:958	arg1	insights					960:967	molecular insights	950:967	molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells	950:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	6	58	theme	B-cell-specific	1094:1108	arg1	target					1144:1149	a therapeutic target	1130:1149	a therapeutic target for depleting dysregulated B cells	1130:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	6	58	theme	B-cell-specific	1094:1108	arg1	CD22					1122:1125	B-cell-specific co-receptor CD22	1094:1125	B-cell-specific co-receptor CD22	1094:1125	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	5	59	from	resolution	833:842	arg1	epratuzumab					812:822	the therapeutic antibody epratuzumab	787:822	the therapeutic antibody epratuzumab at 3.1 Å resolution	787:842	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	1	60	theme	inhibition	108:117	arg1	level					92:96	a baseline level	81:96	a baseline level of B-cell inhibition	81:117	CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check.
28970495	5	61	theme	antibody	909:916	arg1	engagement					918:927	antibody engagement	909:927	antibody engagement	909:927	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	4	62	from	autoimmunity	710:721	arg1	mammals					726:732	mammals	726:732	mammals	726:732	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	6	63	theme	immune	1050:1055	arg1	modulators					1057:1066	immune modulators	1050:1066	immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells	1050:1184	Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells.
28970495	5	64	theme	3.1 Å	827:831	arg1	resolution					833:842	3.1 Å resolution	827:842	3.1 Å resolution	827:842	We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement.
28970495	3	65	theme	pre-formed	444:453	arg1	β-hairpin					455:463	a pre-formed β-hairpin	442:463	a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins	442:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	4	66	theme	extended	583:590	arg1	conformation					592:603	an extended conformation	580:603	an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals	580:732	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	4	67	from	binding	676:682	arg1	cells					666:670	B cells	664:670	B cells	664:670	The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals.
28970495	2	68	theme	B	237:237	arg1	cells					239:243	dysregulated B cells	224:243	dysregulated B cells that cause autoimmune diseases and blood cancers	224:292	As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers.
28970495	1	69	theme	humoral	127:133	arg1	immunity					135:142	humoral immunity	127:142	humoral immunity	127:142	CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check.
28970495	7	70	theme	B-cell	1393:1398	arg1	activation					1400:1409	B-cell activation	1393:1409	B-cell activation	1393:1409	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28970495	3	71	theme	crystal	314:320	arg1	structure					322:330	the crystal structure	310:330	the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins	310:550	Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins.
28970495	2	72	theme	dysregulated	224:235	arg1	cells					239:243	dysregulated B cells	224:243	dysregulated B cells that cause autoimmune diseases and blood cancers	224:292	As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers.
28970495	7	73	theme	antibody	1314:1321	arg1	epratuzumab					1323:1333	the bound therapeutic antibody epratuzumab	1292:1333	the bound therapeutic antibody epratuzumab	1292:1333	Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.
28700571	2	0	from	trimer	333:338	arg1	surface					347:353	the surface	343:353	the surface of HIV	343:360	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	7	1	theme	7.4 Å	1337:1341	arg1	resolution					1343:1352	7.4 Å resolution	1337:1352	7.4 Å resolution	1337:1352	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	2	theme	antibody	1302:1309	arg1	PGV04					1311:1315	the CD4-binding-site antibody PGV04	1281:1315	the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1281:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	9	3	theme	formed	1770:1775	arg1	pocket					1777:1782	a newly formed pocket	1762:1782	a newly formed pocket	1762:1782	Both CD4 and b12 induce large, previously uncharacterized conformational rearrangements in the gp41 subunits, and the fusion peptide becomes buried in a newly formed pocket.
28700571	3	4	gly	glycosylation	517:529	arg2	sites					531:535	N-linked glycosylation sites	508:535	N-linked glycosylation sites that contribute roughly half the mass of Env	508:580	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	1	5	theme	events	194:199	arg1	series					184:189	a series	182:189	a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication	182:298	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	4	6	theme	Env	724:726	arg1	trimers					728:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	6	theme	Env	724:726	arg1	mimics					765:770	structural and antigenic mimics	740:770	structural and antigenic mimics of the pre-fusion native, surface-presented Env	740:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	6	7	theme	antibody	1062:1069	arg1	17b					1071:1073	antibody 17b	1062:1073	antibody 17b	1062:1073	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	8	attach	present	943:949	arg1	resolutions					1101:1111	resolutions	1101:1111	resolutions of 3.7 Å and 3.6 Å	1101:1130	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	8	attach	present	943:949	arg2	we					940:941	we	940:941	we	940:941	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	9	theme	3.6 Å	1126:1130	arg1	resolutions					1101:1111	resolutions	1101:1111	resolutions of 3.7 Å and 3.6 Å	1101:1130	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	3	10	theme	high	438:441	arg1	degree					443:448	a high degree	436:448	a high degree of mutation in five variable regions (V1-V5)	436:493	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	8	11	theme	host	1599:1602	arg1	cells					1604:1608	host cells	1599:1608	host cells	1599:1608	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	3	12	theme	receptor	623:630	arg1	recognition					608:618	recognition	608:618	recognition of receptor CD4 and co-receptor CXCR4/CCR5	608:661	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	6	13	theme	3.7 Å	1116:1120	arg1	resolutions					1101:1111	resolutions	1101:1111	resolutions of 3.7 Å and 3.6 Å	1101:1130	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	3	14	theme	variable	470:477	arg1	V1-V5					488:492	V1-V5	488:492	V1-V5	488:492	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	3	14	theme	variable	470:477	arg1	regions					479:485	five variable regions	465:485	five variable regions (V1-V5)	465:493	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	10	15	theme	biological	1829:1838	arg1	function					1840:1847	the biological function	1825:1847	the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design	1825:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	9	16	dep	large	1635:1639	arg1	uncharacterized					1653:1667	uncharacterized	1653:1667	uncharacterized	1653:1667	Both CD4 and b12 induce large, previously uncharacterized conformational rearrangements in the gp41 subunits, and the fusion peptide becomes buried in a newly formed pocket.
28700571	6	17	from	complex	1041:1047	arg1	structures					992:1001	high-resolution cryo-electron microscopy structures	951:1001	high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	951:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	10	18	theme	viral	1863:1867	arg1	fusion					1869:1874	the type I viral fusion	1852:1874	the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design	1852:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	7	19	from	resolution	1343:1352	arg1	CD4					1274:1276	CD4	1274:1276	CD4	1274:1276	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	19	from	resolution	1343:1352	arg1	PGV04					1311:1315	the CD4-binding-site antibody PGV04	1281:1315	the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1281:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	10	20	theme	type	1856:1859	arg1	fusion					1869:1874	the type I viral fusion	1852:1874	the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design	1852:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	4	21	theme	native	790:795	arg1	Env					816:818	the pre-fusion native, surface-presented Env	775:818	the pre-fusion native, surface-presented Env	775:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	10	22	theme	HIV-1	1889:1893	arg1	templates					1910:1918	HIV-1 as well as new templates	1889:1918	HIV-1 as well as new templates for inhibitor design	1889:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	4	23	theme	neutralizing	848:859	arg1	antibodies					861:870	broadly neutralizing antibodies	840:870	broadly neutralizing antibodies	840:870	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	7	24	theme	Env	1221:1223	arg1	trimers					1225:1231	B41 SOSIP Env trimers	1211:1231	B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1211:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	25	with	trimers	1225:1231	arg1	ligand					1241:1246	no ligand	1238:1246	no ligand	1238:1246	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	1	26	from	s	138:138	arg1	cell					151:154	a host cell	144:154	a host cell	144:154	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	8	27	theme	molecular	1499:1507	arg1	basis					1509:1513	the molecular basis	1495:1513	the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells	1495:1608	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	9	28	theme	large	1635:1639	arg1	rearrangements					1684:1697	large, previously uncharacterized conformational rearrangements	1635:1697	large, previously uncharacterized conformational rearrangements	1635:1697	Both CD4 and b12 induce large, previously uncharacterized conformational rearrangements in the gp41 subunits, and the fusion peptide becomes buried in a newly formed pocket.
28700571	10	29	theme	new	1906:1908	arg1	templates					1910:1918	HIV-1 as well as new templates	1889:1918	HIV-1 as well as new templates for inhibitor design	1889:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	0	30	theme	HIV-1	66:70	arg1	spike					81:85	the HIV-1 envelope spike	62:85	the HIV-1 envelope spike	62:85	Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.
28700571	3	31	dep	receptor	623:630	arg1	CD4					632:634	CD4	632:634	CD4	632:634	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	3	31	dep	receptor	623:630	arg1	CXCR4/CCR5					652:661	co-receptor CXCR4/CCR5	640:661	co-receptor CXCR4/CCR5	640:661	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	3	32	theme	viral	695:699	arg1	fitness					701:707	viral fitness	695:707	viral fitness	695:707	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	1	33	theme	material	275:282	arg1	fusion					216:221	fusion	216:221	fusion with the host cell membrane	216:249	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	1	33	theme	material	275:282	arg1	transfer					255:262	transfer	255:262	transfer of genetic material for replication	255:298	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	2	34	gly	glycoprotein	314:325	arg1	glycoprotein					314:325	envelope glycoprotein	305:325	The envelope glycoprotein (Env) trimer on the surface of HIV	301:360	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	2	34	gly	glycoprotein	314:325	arg1	Env					328:330	Env	328:330	Env	328:330	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	7	35	with	complex	1254:1260	arg1	CD4					1274:1276	CD4	1274:1276	CD4	1274:1276	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	35	with	complex	1254:1260	arg1	PGV04					1311:1315	the CD4-binding-site antibody PGV04	1281:1315	the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1281:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	36	theme	SOSIP	1215:1219	arg1	trimers					1225:1231	B41 SOSIP Env trimers	1211:1231	B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1211:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	2	37	theme	HIV	358:360	arg1	surface					347:353	the surface	343:353	the surface of HIV	343:360	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	2	38	theme	envelope	305:312	arg1	glycoprotein					314:325	envelope glycoprotein	305:325	The envelope glycoprotein (Env) trimer on the surface of HIV	301:360	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	2	38	theme	envelope	305:312	arg1	Env					328:330	Env	328:330	Env	328:330	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	0	39	theme	Open	0:3	arg1	structures					16:25	Open and closed structures	0:25	Open and closed structures	0:25	Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.
28700571	8	40	theme	complete	1403:1410	arg1	description					1412:1422	the most complete description	1394:1422	the most complete description	1394:1422	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	0	41	theme	closed	9:14	arg1	structures					16:25	Open and closed structures	0:25	Open and closed structures	0:25	Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.
28700571	1	42	theme	many	92:95	arg1	viruses					107:113	many enveloped viruses	92:113	many enveloped viruses	92:113	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	7	43	theme	microscopy	1181:1190	arg1	reconstructions					1192:1206	cryo-electron microscopy reconstructions	1167:1206	cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1167:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	2	44	theme	receptor	381:388	arg1	binding					390:396	receptor binding	381:396	receptor binding	381:396	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	3	45	theme	glycosylation	517:529	arg1	sites					531:535	N-linked glycosylation sites	508:535	N-linked glycosylation sites that contribute roughly half the mass of Env	508:580	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	4	46	theme	Soluble	710:716	arg1	trimers					728:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	46	theme	Soluble	710:716	arg1	mimics					765:770	structural and antigenic mimics	740:770	structural and antigenic mimics of the pre-fusion native, surface-presented Env	740:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	10	47	theme	key	1810:1812	arg1	details					1814:1820	key details	1810:1820	key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design	1810:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	1	48	theme	cell	237:240	arg1	membrane					242:249	the host cell membrane	228:249	the host cell membrane	228:249	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	5	49	theme	vaccine	914:920	arg1	development					922:932	vaccine development	914:932	vaccine development	914:932	Thus, they are attractive immunogens for vaccine development.
28700571	6	50	theme	Env	1026:1028	arg1	trimers					1030:1036	subtype B B41 SOSIP Env trimers	1006:1036	subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	1006:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	9	51	theme	fusion	1729:1734	arg1	peptide					1736:1742	the fusion peptide	1725:1742	the fusion peptide	1725:1742	Both CD4 and b12 induce large, previously uncharacterized conformational rearrangements in the gp41 subunits, and the fusion peptide becomes buried in a newly formed pocket.
28700571	7	52	from	reconstructions	1192:1206	arg1	complex					1254:1260	complex	1254:1260	complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1254:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	6	53	theme	B41	1016:1018	arg1	trimers					1030:1036	subtype B B41 SOSIP Env trimers	1006:1036	subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	1006:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	54	from	structures	992:1001	arg1	complex					1041:1047	complex	1041:1047	complex with CD4 and antibody 17b, or with antibody b12	1041:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	55	theme	subtype	1006:1012	arg1	trimers					1030:1036	subtype B B41 SOSIP Env trimers	1006:1036	subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	1006:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	3	56	link	N-linked	508:515	arg1	sites					531:535	N-linked glycosylation sites	508:535	N-linked glycosylation sites that contribute roughly half the mass of Env	508:580	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	8	57	theme	CD4-17b-induced	1454:1468	arg1	intermediate					1470:1481	the CD4-17b-induced intermediate	1450:1481	the CD4-17b-induced intermediate	1450:1481	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	8	58	theme	conformational	1547:1560	arg1	change					1562:1567	the receptor-binding-induced conformational change	1518:1567	the receptor-binding-induced conformational change required for HIV-1 entry into host cells	1518:1608	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	3	59	dep	contribute	542:551	arg1	half					561:564	half	561:564	half	561:564	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	4	60	theme	structural	740:749	arg1	trimers					728:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	60	theme	structural	740:749	arg1	mimics					765:770	structural and antigenic mimics	740:770	structural and antigenic mimics of the pre-fusion native, surface-presented Env	740:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	61	theme	antigenic	755:763	arg1	trimers					728:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	61	theme	antigenic	755:763	arg1	mimics					765:770	structural and antigenic mimics	740:770	structural and antigenic mimics of the pre-fusion native, surface-presented Env	740:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	8	62	theme	HIV-1	1582:1586	arg1	entry					1588:1592	HIV-1 entry	1582:1592	HIV-1 entry into host cells	1582:1608	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	4	63	theme	SOSIP	718:722	arg1	trimers					728:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	63	theme	SOSIP	718:722	arg1	mimics					765:770	structural and antigenic mimics	740:770	structural and antigenic mimics of the pre-fusion native, surface-presented Env	740:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	1	64	with	fusion	216:221	arg1	membrane					242:249	the host cell membrane	228:249	the host cell membrane	228:249	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	7	65	theme	CD4-binding-site	1285:1300	arg1	PGV04					1311:1315	the CD4-binding-site antibody PGV04	1281:1315	the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1281:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	3	66	theme	functional	587:596	arg1	sites					598:602	the functional sites	583:602	the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5	583:661	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	7	67	from	5.6 Å	1320:1324	arg1	CD4					1274:1276	CD4	1274:1276	CD4	1274:1276	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	67	from	5.6 Å	1320:1324	arg1	PGV04					1311:1315	the CD4-binding-site antibody PGV04	1281:1315	the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1281:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	3	68	theme	mutation	453:460	arg1	degree					443:448	a high degree	436:448	a high degree of mutation in five variable regions (V1-V5)	436:493	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	1	69	theme	host	146:149	arg1	cell					151:154	a host cell	144:154	a host cell	144:154	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	7	70	from	5.2 Å	1327:1331	arg1	CD4					1274:1276	CD4	1274:1276	CD4	1274:1276	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	70	from	5.2 Å	1327:1331	arg1	PGV04					1311:1315	the CD4-binding-site antibody PGV04	1281:1315	the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1281:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	6	71	with	complex	1041:1047	arg1	b12					1093:1095	antibody b12	1084:1095	antibody b12	1084:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	71	with	complex	1041:1047	arg1	CD4					1054:1056	CD4	1054:1056	CD4	1054:1056	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	4	72	theme	Env	816:818	arg1	targets					829:835	targets	829:835	targets of broadly neutralizing antibodies	829:870	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	72	theme	Env	816:818	arg1	trimers					728:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	72	theme	Env	816:818	arg1	mimics					765:770	structural and antigenic mimics	740:770	structural and antigenic mimics of the pre-fusion native, surface-presented Env	740:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	10	73	theme	I	1861:1861	arg1	fusion					1869:1874	the type I viral fusion	1852:1874	the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design	1852:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	1	74	from	step	174:177	arg1	series					184:189	a series	182:189	a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication	182:298	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	1	75	theme	enveloped	97:105	arg1	viruses					107:113	many enveloped viruses	92:113	many enveloped viruses	92:113	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	10	76	from	details	1814:1820	arg1	function					1840:1847	the biological function	1825:1847	the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design	1825:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	3	77	from	mutation	453:460	arg1	V1-V5					488:492	V1-V5	488:492	V1-V5	488:492	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	3	77	from	mutation	453:460	arg1	regions					479:485	five variable regions	465:485	five variable regions (V1-V5)	465:493	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	3	78	theme	co-receptor	640:650	arg1	CXCR4/CCR5					652:661	co-receptor CXCR4/CCR5	640:661	co-receptor CXCR4/CCR5	640:661	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	4	79	theme	pre-fusion	779:788	arg1	Env					816:818	the pre-fusion native, surface-presented Env	775:818	the pre-fusion native, surface-presented Env	775:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	6	80	theme	antibody	1084:1091	arg1	b12					1093:1095	antibody b12	1084:1095	antibody b12	1084:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	4	81	dep	native	790:795	arg1	surface-presented					798:814	surface-presented	798:814	surface-presented	798:814	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	7	82	theme	trimers	1225:1231	arg1	reconstructions					1192:1206	cryo-electron microscopy reconstructions	1167:1206	cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1167:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	10	83	theme	fusion	1869:1874	arg1	function					1840:1847	the biological function	1825:1847	the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design	1825:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	0	84	theme	envelope	72:79	arg1	spike					81:85	the HIV-1 envelope spike	62:85	the HIV-1 envelope spike	62:85	Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.
28700571	1	85	theme	receptor	129:136	arg1	s					138:138	a receptor(s)	127:139	a receptor(s) on a host cell	127:154	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	4	86	theme	antibodies	861:870	arg1	targets					829:835	targets	829:835	targets of broadly neutralizing antibodies	829:870	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	86	theme	antibodies	861:870	arg1	trimers					728:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers	710:734	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	4	86	theme	antibodies	861:870	arg1	mimics					765:770	structural and antigenic mimics	740:770	structural and antigenic mimics of the pre-fusion native, surface-presented Env	740:818	Soluble SOSIP Env trimers are structural and antigenic mimics of the pre-fusion native, surface-presented Env, and are targets of broadly neutralizing antibodies.
28700571	3	87	from	degree	443:448	arg1	V1-V5					488:492	V1-V5	488:492	V1-V5	488:492	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	3	87	from	degree	443:448	arg1	regions					479:485	five variable regions	465:485	five variable regions (V1-V5)	465:493	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	1	88	theme	genetic	267:273	arg1	material					275:282	genetic material	267:282	genetic material for replication	267:298	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	1	89	with	transfer	255:262	arg1	membrane					242:249	the host cell membrane	228:249	the host cell membrane	228:249	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	0	90	from	pliability	48:57	arg1	spike					81:85	the HIV-1 envelope spike	62:85	the HIV-1 envelope spike	62:85	Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.
28700571	7	91	from	trimers	1225:1231	arg1	complex					1254:1260	complex	1254:1260	complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1254:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	6	92	theme	microscopy	981:990	arg1	structures					992:1001	high-resolution cryo-electron microscopy structures	951:1001	high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	951:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	9	93	theme	conformational	1669:1682	arg1	rearrangements					1684:1697	large, previously uncharacterized conformational rearrangements	1635:1697	large, previously uncharacterized conformational rearrangements	1635:1697	Both CD4 and b12 induce large, previously uncharacterized conformational rearrangements in the gp41 subunits, and the fusion peptide becomes buried in a newly formed pocket.
28700571	0	94	from	allostery	34:42	arg1	spike					81:85	the HIV-1 envelope spike	62:85	the HIV-1 envelope spike	62:85	Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike.
28700571	2	95	theme	glycoprotein	314:325	arg1	responsible					365:375	responsible	365:375	responsible	365:375	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	2	95	theme	glycoprotein	314:325	arg1	trimer					333:338	The envelope glycoprotein (Env) trimer	301:338	The envelope glycoprotein (Env) trimer on the surface of HIV	301:360	The envelope glycoprotein (Env) trimer on the surface of HIV is responsible for receptor binding and fusion.
28700571	6	96	theme	high-resolution	951:965	arg1	microscopy					981:990	high-resolution cryo-electron microscopy	951:990	high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	951:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	3	97	from	regions	479:485	arg1	degree					443:448	a high degree	436:448	a high degree of mutation in five variable regions (V1-V5)	436:493	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	7	98	theme	cryo-electron	1167:1179	arg1	microscopy					1181:1190	cryo-electron microscopy	1167:1190	cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1167:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	5	99	theme	attractive	888:897	arg1	they					879:882	they	879:882	they	879:882	Thus, they are attractive immunogens for vaccine development.
28700571	5	99	theme	attractive	888:897	arg1	immunogens					899:908	attractive immunogens	888:908	attractive immunogens for vaccine development	888:932	Thus, they are attractive immunogens for vaccine development.
28700571	7	100	from	complex	1254:1260	arg1	reconstructions					1192:1206	cryo-electron microscopy reconstructions	1167:1206	cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1167:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	7	101	theme	B41	1211:1213	arg1	trimers					1225:1231	B41 SOSIP Env trimers	1211:1231	B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively	1211:1366	We compare these to cryo-electron microscopy reconstructions of B41 SOSIP Env trimers with no ligand or in complex with either CD4 or the CD4-binding-site antibody PGV04 at 5.6 Å, 5.2 Å and 7.4 Å resolution, respectively.
28700571	3	102	theme	N-linked	508:515	arg1	sites					531:535	N-linked glycosylation sites	508:535	N-linked glycosylation sites that contribute roughly half the mass of Env	508:580	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	1	103	theme	host	232:235	arg1	membrane					242:249	the host cell membrane	228:249	the host cell membrane	228:249	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	6	104	theme	trimers	1030:1036	arg1	structures					992:1001	high-resolution cryo-electron microscopy structures	951:1001	high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	951:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	105	from	trimers	1030:1036	arg1	complex					1041:1047	complex	1041:1047	complex with CD4 and antibody 17b, or with antibody b12	1041:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	106	theme	SOSIP	1020:1024	arg1	trimers					1030:1036	subtype B B41 SOSIP Env trimers	1006:1036	subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	1006:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	10	107	theme	inhibitor	1924:1932	arg1	design					1934:1939	inhibitor design	1924:1939	inhibitor design	1924:1939	These structures provide key details on the biological function of the type I viral fusion machine from HIV-1 as well as new templates for inhibitor design.
28700571	8	108	theme	receptor-binding-induced	1522:1545	arg1	change					1562:1567	the receptor-binding-induced conformational change	1518:1567	the receptor-binding-induced conformational change required for HIV-1 entry into host cells	1518:1608	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	1	109	theme	first	168:172	arg1	step					174:177	the first step	164:177	the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication	164:298	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	1	109	theme	first	168:172	arg1	binding					116:122	binding	116:122	binding to a receptor(s) on a host cell	116:154	For many enveloped viruses, binding to a receptor(s) on a host cell acts as the first step in a series of events culminating in fusion with the host cell membrane and transfer of genetic material for replication.
28700571	6	110	theme	B	1014:1014	arg1	trimers					1030:1036	subtype B B41 SOSIP Env trimers	1006:1036	subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	1006:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	6	111	theme	cryo-electron	967:979	arg1	microscopy					981:990	high-resolution cryo-electron microscopy	951:990	high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12	951:1095	Here we present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP Env trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively.
28700571	8	112	theme	intermediate	1470:1481	arg1	knowledge					1436:1444	our knowledge	1432:1444	our knowledge	1432:1444	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
28700571	3	113	theme	Env	578:580	arg1	mass					570:573	the mass	566:573	the mass of Env	566:580	Although Env can tolerate a high degree of mutation in five variable regions (V1-V5), and also at N-linked glycosylation sites that contribute roughly half the mass of Env, the functional sites for recognition of receptor CD4 and co-receptor CXCR4/CCR5 are conserved and essential for viral fitness.
28700571	8	114	theme	change	1562:1567	arg1	basis					1509:1513	the molecular basis	1495:1513	the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells	1495:1608	Consequently, we present the most complete description yet, to our knowledge, of the CD4-17b-induced intermediate and provide the molecular basis of the receptor-binding-induced conformational change required for HIV-1 entry into host cells.
29649119	0	0	theme	Protein	71:77	arg1	SV2C					88:91	the Human Protein Receptor SV2C	61:91	the Human Protein Receptor SV2C	61:91	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	7	1	located	observed	1155:1162	arg2	BoNT/A1					1135:1141	BoNT/A1	1135:1141	BoNT/A1	1135:1141	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	7	1	located	observed	1155:1162	arg1	clinic					1171:1176	the clinic	1167:1176	the clinic	1167:1176	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	1	2	theme	major	225:229	arg1	serotypes					231:239	seven major serotypes	219:239	seven major serotypes (BoNT/A-G)	219:250	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	1	2	theme	major	225:229	arg1	BoNT/A-G					242:249	BoNT/A-G	242:249	BoNT/A-G	242:249	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	0	3	theme	Human	65:69	arg1	SV2C					88:91	the Human Protein Receptor SV2C	61:91	the Human Protein Receptor SV2C	61:91	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	0	4	from	Structure	8:16	arg1	Complex					48:54	Complex	48:54	Complex with the Human Protein Receptor SV2C	48:91	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	2	5	used	utilized	302:309	arg2	BoNT/B1					283:289	BoNT/B1	283:289	BoNT/B1	283:289	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	2	5	used	utilized	302:309	arg2	BoNT/A1					271:277	BoNT/A1	271:277	BoNT/A1	271:277	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	2	5	used	utilized	302:309	arg2	Members					253:259	Members	253:259	Members of BoNTs	253:268	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	3	6	theme	promising	449:457	arg1	properties					471:480	promising therapeutic properties	449:480	promising therapeutic properties	449:480	The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties.
29649119	4	7	theme	protein	551:557	arg1	SV2					559:561	synaptic vesicle protein SV2	534:561	synaptic vesicle protein SV2 (SV2A, B, and C)	534:578	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	0	8	theme	Receptor	79:86	arg1	SV2C					88:91	the Human Protein Receptor SV2C	61:91	the Human Protein Receptor SV2C	61:91	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	6	9	theme	BoNT/A-SV2C	805:815	arg1	complexes					817:825	previously reported BoNT/A-SV2C complexes	785:825	previously reported BoNT/A-SV2C complexes	785:825	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	7	10	theme	binding	1016:1022	arg1	interface					1024:1032	the binding interface	1012:1032	the binding interface	1012:1032	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	4	11	theme	vesicle	543:549	arg1	SV2					559:561	synaptic vesicle protein SV2	534:561	synaptic vesicle protein SV2 (SV2A, B, and C)	534:578	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	6	12	theme	reported	796:803	arg1	complexes					817:825	previously reported BoNT/A-SV2C complexes	785:825	previously reported BoNT/A-SV2C complexes	785:825	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	5	13	theme	luminal	741:747	arg1	domain					749:754	the human SV2C luminal domain	726:754	the human SV2C luminal domain	726:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	2	14	theme	medical	344:350	arg1	conditions					352:361	medical conditions	344:361	medical conditions	344:361	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	7	15	from	differences	981:991	arg1	residues					1000:1007	key residues	996:1007	key residues at the binding interface	996:1032	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	7	15	from	differences	981:991	arg1	interface					1024:1032	the binding interface	1012:1032	the binding interface	1012:1032	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	4	16	theme	synaptic	534:541	arg1	SV2					559:561	synaptic vesicle protein SV2	534:561	synaptic vesicle protein SV2 (SV2A, B, and C)	534:578	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	7	17	theme	key	996:998	arg1	residues					1000:1007	key residues	996:1007	key residues at the binding interface	996:1032	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	5	18	from	structure	661:669	arg1	complex					713:719	complex	713:719	complex with the human SV2C luminal domain	713:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	6	19	from	shift	834:838	arg1	BoNT/A2					875:881	BoNT/A2	875:881	BoNT/A2	875:881	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	4	20	theme	protein	589:595	arg1	receptors					597:605	their protein receptors	583:605	their protein receptors	583:605	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	4	20	theme	protein	589:595	arg1	isoforms					522:529	three isoforms	516:529	three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C)	516:578	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	0	21	theme	Crystal	0:6	arg1	Structure					8:16	Crystal Structure	0:16	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C	0:91	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	4	22	dep	SV2	559:561	arg1	B					570:570	B	570:570	B	570:570	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	4	22	dep	SV2	559:561	arg1	C					577:577	C	577:577	C	577:577	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	4	22	dep	SV2	559:561	arg1	SV2A					564:567	SV2A	564:567	SV2A	564:567	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	2	23	theme	increasing	323:332	arg1	number					334:339	an increasing number	320:339	an increasing number of medical conditions	320:361	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	0	24	theme	Botulinum	21:29	arg1	Neurotoxin					31:40	Botulinum Neurotoxin	21:40	Botulinum Neurotoxin A2	21:43	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	0	25	theme	Receptor	115:122	arg1	Binding					124:130	Receptor Binding	115:130	Receptor Binding	115:130	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	5	26	with	complex	713:719	arg1	domain					749:754	the human SV2C luminal domain	726:754	the human SV2C luminal domain	726:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	5	27	theme	SV2C	736:739	arg1	domain					749:754	the human SV2C luminal domain	726:754	the human SV2C luminal domain	726:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	5	28	theme	human	730:734	arg1	domain					749:754	the human SV2C luminal domain	726:754	the human SV2C luminal domain	726:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	2	29	theme	BoNTs	264:268	arg1	Members					253:259	Members	253:259	Members of BoNTs	253:268	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	2	29	theme	BoNTs	264:268	arg1	BoNT/B1					283:289	BoNT/B1	283:289	BoNT/B1	283:289	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	2	29	theme	BoNTs	264:268	arg1	BoNT/A1					271:277	BoNT/A1	271:277	BoNT/A1	271:277	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	3	30	theme	therapeutic	459:469	arg1	properties					471:480	promising therapeutic properties	449:480	promising therapeutic properties	449:480	The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties.
29649119	0	31	theme	A2	42:43	arg1	Structure					8:16	Crystal Structure	0:16	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C	0:91	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	6	32	theme	segment	864:870	arg1	shift					834:838	a shift	832:838	a shift of the receptor-binding segment in BoNT/A2	832:881	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	5	33	theme	high	626:629	arg1	Å					647:647	2.0 Å	643:647	2.0 Å	643:647	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	5	33	theme	high	626:629	arg1	resolution					631:640	high resolution	626:640	a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain	624:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	6	34	theme	interaction	962:972	arg1	behavior					946:953	the dynamic behavior	934:953	the dynamic behavior of the interaction	934:972	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	1	35	theme	dangerous	186:194	arg1	toxins					206:211	highly dangerous bacterial toxins	179:211	highly dangerous bacterial toxins	179:211	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	0	36	theme	Neurotoxin	31:40	arg1	A2					42:43	Botulinum Neurotoxin A2	21:43	Botulinum Neurotoxin A2	21:43	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	6	37	theme	receptor-binding	847:862	arg1	segment					864:870	the receptor-binding segment	843:870	the receptor-binding segment	843:870	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	3	38	theme	clinical	368:375	arg1	ongoing					388:394	ongoing	388:394	ongoing	388:394	The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties.
29649119	3	38	theme	clinical	368:375	arg1	trials					377:382	The clinical trials	364:382	The clinical trials	364:382	The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties.
29649119	7	39	theme	different	1063:1071	arg1	isoforms					1077:1084	different SV2 isoforms	1063:1084	different SV2 isoforms	1063:1084	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	2	40	theme	conditions	352:361	arg1	number					334:339	an increasing number	320:339	an increasing number of medical conditions	320:361	Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions.
29649119	5	41	theme	domain	703:708	arg1	structure					661:669	a high resolution (2.0 Å) co-crystal structure	624:669	a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain	624:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	7	42	theme	Small	975:979	arg1	differences					981:991	Small differences	975:991	Small differences in key residues at the binding interface	975:1032	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	6	43	theme	dynamic	938:944	arg1	behavior					946:953	the dynamic behavior	934:953	the dynamic behavior of the interaction	934:972	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	5	44	theme	resolution	631:640	arg1	structure					661:669	a high resolution (2.0 Å) co-crystal structure	624:669	a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain	624:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	7	45	from	interface	1024:1032	arg1	residues					1000:1007	key residues	996:1007	key residues at the binding interface	996:1032	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	7	45	from	interface	1024:1032	arg1	differences					981:991	Small differences	975:991	Small differences in key residues at the binding interface	975:1032	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
29649119	1	46	with	family	169:174	arg1	serotypes					231:239	seven major serotypes	219:239	seven major serotypes (BoNT/A-G)	219:250	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	1	46	with	family	169:174	arg1	BoNT/A-G					242:249	BoNT/A-G	242:249	BoNT/A-G	242:249	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	0	47	from	Plasticity	101:110	arg1	Binding					124:130	Receptor Binding	115:130	Receptor Binding	115:130	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	6	48	from	SV2C	891:894	arg1	dimensions					903:912	two dimensions	899:912	two dimensions	899:912	The structure is similar to previously reported BoNT/A-SV2C complexes, but a shift of the receptor-binding segment in BoNT/A2 rotates SV2C in two dimensions giving insight into the dynamic behavior of the interaction.
29649119	1	49	theme	toxins	206:211	arg1	neurotoxins					143:153	Botulinum neurotoxins	133:153	Botulinum neurotoxins (BoNTs)	133:161	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	1	49	theme	toxins	206:211	arg1	family					169:174	a family	167:174	a family of highly dangerous bacterial toxins	167:211	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	5	50	theme	BoNT/A2	678:684	arg1	domain					703:708	the BoNT/A2 receptor-binding domain	674:708	the BoNT/A2 receptor-binding domain	674:708	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	0	51	with	Complex	48:54	arg1	SV2C					88:91	the Human Protein Receptor SV2C	61:91	the Human Protein Receptor SV2C	61:91	Crystal Structure of Botulinum Neurotoxin A2 in Complex with the Human Protein Receptor SV2C Reveals Plasticity in Receptor Binding.
29649119	3	52	theme	BoNT/A	428:433	arg1	BoNT/A2					400:406	BoNT/A2	400:406	BoNT/A2	400:406	The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties.
29649119	3	52	theme	BoNT/A	428:433	arg1	subtype					417:423	another subtype	409:423	another subtype of BoNT/A	409:433	The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties.
29649119	4	53	theme	SV2	559:561	arg1	receptors					597:605	their protein receptors	583:605	their protein receptors	583:605	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	4	53	theme	SV2	559:561	arg1	isoforms					522:529	three isoforms	516:529	three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C)	516:578	Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors.
29649119	5	54	theme	co-crystal	650:659	arg1	structure					661:669	a high resolution (2.0 Å) co-crystal structure	624:669	a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain	624:754	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	1	55	theme	bacterial	196:204	arg1	toxins					206:211	highly dangerous bacterial toxins	179:211	highly dangerous bacterial toxins	179:211	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	1	56	theme	Botulinum	133:141	arg1	neurotoxins					143:153	Botulinum neurotoxins	133:153	Botulinum neurotoxins (BoNTs)	133:161	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	1	56	theme	Botulinum	133:141	arg1	family					169:174	a family	167:174	a family of highly dangerous bacterial toxins	167:211	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	1	56	theme	Botulinum	133:141	arg1	BoNTs					156:160	BoNTs	156:160	BoNTs	156:160	Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G).
29649119	5	57	theme	receptor-binding	686:701	arg1	domain					703:708	the BoNT/A2 receptor-binding domain	674:708	the BoNT/A2 receptor-binding domain	674:708	We here present a high resolution (2.0 Å) co-crystal structure of the BoNT/A2 receptor-binding domain in complex with the human SV2C luminal domain.
29649119	7	58	theme	SV2	1073:1075	arg1	isoforms					1077:1084	different SV2 isoforms	1063:1084	different SV2 isoforms	1063:1084	Small differences in key residues at the binding interface may influence the binding to different SV2 isoforms, which may contribute to the differences between BoNT/A1 and BoNT/A2 observed in the clinic.
30028870	2	0	theme	homologous	349:358	arg1	subunits					360:367	five identical or homologous subunits	331:367	five identical or homologous subunits	331:367	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	10	1	theme	binding	1877:1883	arg1	activity					1885:1892	high affinity agonist binding activity	1855:1892	high affinity agonist binding activity	1855:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	1	2	theme	central	267:273	arg1	system					283:288	the central nervous system	263:288	the central nervous system	263:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	8	3	theme	cytoplasmic	1342:1352	arg1	loop					1354:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	10	4	theme	affinity	1860:1867	arg1	activity					1885:1892	high affinity agonist binding activity	1855:1892	high affinity agonist binding activity	1855:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	1	5	theme	GABAA	170:174	arg1	receptors					176:184	GABAA receptors	170:184	GABAA receptors	170:184	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	7	6	theme	assemblies	1214:1223	arg1	formation					1188:1196	formation	1188:1196	formation of monodisperse assemblies	1188:1223	In contrast to expression of α1 alone, co-expression with the β subunit promoted formation of monodisperse assemblies.
30028870	8	7	theme	large	1297:1301	arg1	truncations					1303:1313	large truncations	1297:1313	large truncations in the non-conserved M3/M4 cytoplasmic loop	1297:1357	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	2	8	theme	pentameric	305:314	arg1	arrangement					316:326	the pentameric arrangement	301:326	the pentameric arrangement of five identical or homologous subunits	301:367	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	4	9	theme	expression	664:673	arg1	protocols					692:700	Robust heterologous expression and purification protocols	644:700	Robust heterologous expression and purification protocols of high expressing receptor constructs	644:739	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	3	10	theme	distinct	512:519	arg1	properties					530:539	distinct receptor properties	512:539	distinct receptor properties	512:539	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	8	11	theme	α	1267:1267	arg1	subunits					1275:1282	the α and β subunits	1263:1282	the α and β subunits	1263:1282	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	9	12	theme	receptor	1578:1585	arg1	expression					1587:1596	GABAA receptor expression	1572:1596	GABAA receptor expression in mammalian cell culture	1572:1622	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	4	13	theme	purification	679:690	arg1	protocols					692:700	Robust heterologous expression and purification protocols	644:700	Robust heterologous expression and purification protocols of high expressing receptor constructs	644:739	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	10	14	theme	functional	1736:1745	arg1	construct					1747:1755	a well-behaving minimal functional construct	1712:1755	a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity	1712:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	1	15	theme	primary	203:209	arg1	gatekeepers					211:221	the primary gatekeepers	199:221	the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system	199:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	1	15	theme	primary	203:209	arg1	channels					119:126	The GABA-gated chloride channels	95:126	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors,	95:185	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	8	16	theme	β	1273:1273	arg1	subunits					1275:1282	the α and β subunits	1263:1282	the α and β subunits	1263:1282	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	4	17	theme	structural	755:764	arg1	studies					766:772	structural studies	755:772	structural studies	755:772	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	10	18	theme	well-behaving	1714:1726	arg1	construct					1747:1755	a well-behaving minimal functional construct	1712:1755	a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity	1712:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	3	19	theme	structural	593:602	arg1	information					604:614	high resolution structural information	577:614	high resolution structural information for heteromeric assemblies	577:641	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	5	20	theme	fluorescence	958:969	arg1	FSEC					1012:1015	FSEC	1012:1015	FSEC	1012:1015	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	20	theme	fluorescence	958:969	arg1	chromatography					996:1009	fluorescence detection size exclusion chromatography	958:1009	fluorescence detection size exclusion chromatography (FSEC)	958:1016	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	21	theme	size	981:984	arg1	FSEC					1012:1015	FSEC	1012:1015	FSEC	1012:1015	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	21	theme	size	981:984	arg1	chromatography					996:1009	fluorescence detection size exclusion chromatography	958:1009	fluorescence detection size exclusion chromatography (FSEC)	958:1016	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	8	22	theme	oligomeric	1380:1389	arg1	assembly					1391:1398	oligomeric assembly	1380:1398	oligomeric assembly	1380:1398	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	5	23	theme	unique	795:800	arg1	approach					802:809	a unique approach	793:809	a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC)	793:1016	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	24	theme	subunit	869:875	arg1	assemblies					877:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	1	25	theme	family	153:158	arg1	channels					119:126	The GABA-gated chloride channels	95:126	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors,	95:185	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	1	25	theme	family	153:158	arg1	gatekeepers					211:221	the primary gatekeepers	199:221	the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system	199:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	0	26	theme	structural	75:84	arg1	studies					86:92	structural studies	75:92	structural studies	75:92	Expression and purification of a functional heteromeric GABAA receptor for structural studies.
30028870	8	27	theme	channel	1414:1420	arg1	activity					1422:1429	GABA-gated channel activity	1403:1429	GABA-gated channel activity	1403:1429	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	9	28	theme	recombinant	1636:1646	arg1	transduction					1660:1671	recombinant baculovirus transduction	1636:1671	recombinant baculovirus transduction	1636:1671	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	6	29	theme	receptor	1029:1036	arg1	expression					1038:1047	receptor expression	1029:1047	receptor expression	1029:1047	To detect receptor expression, GFP fusions were introduced into the α1 subunit isoform.
30028870	0	30	theme	GABAA	56:60	arg1	receptor					62:69	a functional heteromeric GABAA receptor	31:69	a functional heteromeric GABAA receptor for structural studies	31:92	Expression and purification of a functional heteromeric GABAA receptor for structural studies.
30028870	10	31	theme	GABAA	1771:1775	arg1	subtype					1786:1792	the α1/β1 GABAA receptor subtype	1761:1792	the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity	1761:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	2	32	theme	channel	448:454	arg1	properties					456:465	ion channel properties	444:465	ion channel properties	444:465	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	1	33	theme	Cys-loop	135:142	arg1	family					153:158	the Cys-loop receptor family	131:158	the Cys-loop receptor family	131:158	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	5	34	theme	GABAA	854:858	arg1	assemblies					877:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	1	35	theme	nervous	275:281	arg1	system					283:288	the central nervous system	263:288	the central nervous system	263:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	8	36	theme	N-linked	1452:1459	arg1	sites					1475:1479	N-linked glycosylation sites	1452:1479	N-linked glycosylation sites	1452:1479	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	7	37	theme	monodisperse	1201:1212	arg1	assemblies					1214:1223	monodisperse assemblies	1201:1223	monodisperse assemblies	1201:1223	In contrast to expression of α1 alone, co-expression with the β subunit promoted formation of monodisperse assemblies.
30028870	10	38	theme	high	1855:1858	arg1	activity					1885:1892	high affinity agonist binding activity	1855:1892	high affinity agonist binding activity	1855:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	1	39	theme	chloride	110:117	arg1	channels					119:126	The GABA-gated chloride channels	95:126	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors,	95:185	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	1	39	theme	chloride	110:117	arg1	gatekeepers					211:221	the primary gatekeepers	199:221	the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system	199:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	6	40	theme	subunit	1090:1096	arg1	isoform					1098:1104	the α1 subunit isoform	1083:1104	the α1 subunit isoform	1083:1104	To detect receptor expression, GFP fusions were introduced into the α1 subunit isoform.
30028870	8	41	theme	sites	1475:1479	arg1	removal					1441:1447	removal	1441:1447	removal of N-linked glycosylation sites	1441:1479	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	0	42	theme	receptor	62:69	arg1	purification					15:26	purification	15:26	purification	15:26	Expression and purification of a functional heteromeric GABAA receptor for structural studies.
30028870	0	42	theme	receptor	62:69	arg1	Expression					0:9	Expression	0:9	Expression	0:9	Expression and purification of a functional heteromeric GABAA receptor for structural studies.
30028870	3	43	theme	structural	492:501	arg1	basis					503:507	the structural basis	488:507	the structural basis of distinct receptor properties	488:539	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	0	44	theme	heteromeric	44:54	arg1	receptor					62:69	a functional heteromeric GABAA receptor	31:69	a functional heteromeric GABAA receptor for structural studies	31:92	Expression and purification of a functional heteromeric GABAA receptor for structural studies.
30028870	8	45	gly	glycosylation	1461:1473	arg2	sites					1475:1479	N-linked glycosylation sites	1452:1479	N-linked glycosylation sites	1452:1479	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	9	46	theme	cell	1611:1614	arg1	culture					1616:1622	mammalian cell culture	1601:1622	mammalian cell culture	1601:1622	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	3	47	theme	receptor	521:528	arg1	properties					530:539	distinct receptor properties	512:539	distinct receptor properties	512:539	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	1	48	theme	fast	226:229	arg1	neurotransmission					242:258	fast inhibitory neurotransmission	226:258	fast inhibitory neurotransmission	226:258	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	7	49	theme	β	1169:1169	arg1	subunit					1171:1177	the β subunit	1165:1177	the β subunit	1165:1177	In contrast to expression of α1 alone, co-expression with the β subunit promoted formation of monodisperse assemblies.
30028870	7	50	with	co-expression	1146:1158	arg1	subunit					1171:1177	the β subunit	1165:1177	the β subunit	1165:1177	In contrast to expression of α1 alone, co-expression with the β subunit promoted formation of monodisperse assemblies.
30028870	2	51	theme	subunits	360:367	arg1	arrangement					316:326	the pentameric arrangement	301:326	the pentameric arrangement of five identical or homologous subunits	301:367	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	1	52	theme	neurotransmission	242:258	arg1	gatekeepers					211:221	the primary gatekeepers	199:221	the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system	199:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	1	52	theme	neurotransmission	242:258	arg1	channels					119:126	The GABA-gated chloride channels	95:126	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors,	95:185	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	10	53	theme	milligram	1818:1826	arg1	quantities					1828:1837	milligram quantities	1818:1837	milligram quantities	1818:1837	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	7	54	theme	α1	1136:1137	arg1	expression					1122:1131	expression	1122:1131	expression of α1 alone	1122:1143	In contrast to expression of α1 alone, co-expression with the β subunit promoted formation of monodisperse assemblies.
30028870	10	55	theme	agonist	1869:1875	arg1	activity					1885:1892	high affinity agonist binding activity	1855:1892	high affinity agonist binding activity	1855:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	4	56	theme	expressing	710:719	arg1	constructs					730:739	high expressing receptor constructs	705:739	high expressing receptor constructs	705:739	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	5	57	theme	Xenopus	901:907	arg1	oocyte					909:914	the Xenopus oocyte	897:914	the Xenopus oocyte	897:914	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	57	theme	Xenopus	901:907	arg1	host					933:936	an expression host	919:936	an expression host	919:936	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	9	58	from	expression	1587:1596	arg1	culture					1616:1622	mammalian cell culture	1601:1622	mammalian cell culture	1601:1622	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	8	59	theme	Mutagenesis	1226:1236	arg1	experiments					1238:1248	Mutagenesis experiments	1226:1248	Mutagenesis experiments	1226:1248	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	4	60	theme	high	705:708	arg1	constructs					730:739	high expressing receptor constructs	705:739	high expressing receptor constructs	705:739	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	2	61	theme	GABAA	370:374	arg1	subtypes					385:392	GABAA receptor subtypes	370:392	GABAA receptor subtypes	370:392	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	4	62	theme	heterologous	651:662	arg1	expression					664:673	Robust heterologous expression	644:673	Robust heterologous expression	644:673	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	7	63	dep	expression	1122:1131	arg1	contrast					1110:1117	contrast	1110:1117	contrast	1110:1117	In contrast to expression of α1 alone, co-expression with the β subunit promoted formation of monodisperse assemblies.
30028870	2	64	theme	identical	336:344	arg1	subunits					360:367	five identical or homologous subunits	331:367	five identical or homologous subunits	331:367	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	3	65	theme	information	604:614	arg1	absence					566:572	the absence	562:572	the absence of high resolution structural information for heteromeric assemblies	562:641	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	8	66	link	N-linked	1452:1459	arg1	sites					1475:1479	N-linked glycosylation sites	1452:1479	N-linked glycosylation sites	1452:1479	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	10	67	theme	minimal	1728:1734	arg1	construct					1747:1755	a well-behaving minimal functional construct	1712:1755	a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity	1712:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	9	68	theme	GABAA	1572:1576	arg1	expression					1587:1596	GABAA receptor expression	1572:1596	GABAA receptor expression in mammalian cell culture	1572:1622	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	8	69	theme	M3/M4	1336:1340	arg1	loop					1354:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	1	70	from	gatekeepers	211:221	arg1	system					283:288	the central nervous system	263:288	the central nervous system	263:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	5	71	theme	detection	971:979	arg1	FSEC					1012:1015	FSEC	1012:1015	FSEC	1012:1015	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	71	theme	detection	971:979	arg1	chromatography					996:1009	fluorescence detection size exclusion chromatography	958:1009	fluorescence detection size exclusion chromatography (FSEC)	958:1016	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	3	72	theme	heteromeric	620:630	arg1	assemblies					632:641	heteromeric assemblies	620:641	heteromeric assemblies	620:641	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	9	73	theme	mammalian	1601:1609	arg1	culture					1616:1622	mammalian cell culture	1601:1622	mammalian cell culture	1601:1622	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	5	74	theme	expression	922:931	arg1	oocyte					909:914	the Xenopus oocyte	897:914	the Xenopus oocyte	897:914	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	74	theme	expression	922:931	arg1	host					933:936	an expression host	919:936	an expression host	919:936	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	4	75	theme	receptor	721:728	arg1	constructs					730:739	high expressing receptor constructs	705:739	high expressing receptor constructs	705:739	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	8	76	from	truncations	1303:1313	arg1	loop					1354:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	6	77	theme	GFP	1050:1052	arg1	fusions					1054:1060	GFP fusions	1050:1060	GFP fusions	1050:1060	To detect receptor expression, GFP fusions were introduced into the α1 subunit isoform.
30028870	5	78	with	combination	941:951	arg1	FSEC					1012:1015	FSEC	1012:1015	FSEC	1012:1015	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	78	with	combination	941:951	arg1	chromatography					996:1009	fluorescence detection size exclusion chromatography	958:1009	fluorescence detection size exclusion chromatography (FSEC)	958:1016	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	8	79	theme	GABA-gated	1403:1412	arg1	activity					1422:1429	GABA-gated channel activity	1403:1429	GABA-gated channel activity	1403:1429	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	9	80	theme	baculovirus	1648:1658	arg1	transduction					1660:1671	recombinant baculovirus transduction	1636:1671	recombinant baculovirus transduction	1636:1671	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	10	81	theme	α1/β1	1765:1769	arg1	subtype					1786:1792	the α1/β1 GABAA receptor subtype	1761:1792	the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity	1761:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	5	82	theme	functional	843:852	arg1	assemblies					877:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	83	theme	exclusion	986:994	arg1	FSEC					1012:1015	FSEC	1012:1015	FSEC	1012:1015	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	5	83	theme	exclusion	986:994	arg1	chromatography					996:1009	fluorescence detection size exclusion chromatography	958:1009	fluorescence detection size exclusion chromatography (FSEC)	958:1016	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	2	84	theme	ion	444:446	arg1	properties					456:465	ion channel properties	444:465	ion channel properties	444:465	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	2	85	theme	receptor	376:383	arg1	subtypes					385:392	GABAA receptor subtypes	370:392	GABAA receptor subtypes	370:392	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	5	86	theme	receptor	860:867	arg1	assemblies					877:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	1	87	theme	GABA-gated	99:108	arg1	channels					119:126	The GABA-gated chloride channels	95:126	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors,	95:185	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	1	87	theme	GABA-gated	99:108	arg1	gatekeepers					211:221	the primary gatekeepers	199:221	the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system	199:288	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	2	88	theme	subunit	413:419	arg1	composition					421:431	the subunit composition	409:431	the subunit composition that shape ion channel properties	409:465	Formed by the pentameric arrangement of five identical or homologous subunits, GABAA receptor subtypes are defined by the subunit composition that shape ion channel properties.
30028870	0	89	theme	functional	33:42	arg1	receptor					62:69	a functional heteromeric GABAA receptor	31:69	a functional heteromeric GABAA receptor for structural studies	31:92	Expression and purification of a functional heteromeric GABAA receptor for structural studies.
30028870	8	90	theme	non-conserved	1322:1334	arg1	loop					1354:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	the non-conserved M3/M4 cytoplasmic loop	1318:1357	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	6	91	theme	α1	1087:1088	arg1	isoform					1098:1104	the α1 subunit isoform	1083:1104	the α1 subunit isoform	1083:1104	To detect receptor expression, GFP fusions were introduced into the α1 subunit isoform.
30028870	4	92	theme	constructs	730:739	arg1	protocols					692:700	Robust heterologous expression and purification protocols	644:700	Robust heterologous expression and purification protocols of high expressing receptor constructs	644:739	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	8	93	theme	glycosylation	1461:1473	arg1	sites					1475:1479	N-linked glycosylation sites	1452:1479	N-linked glycosylation sites	1452:1479	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	10	94	theme	receptor	1777:1784	arg1	subtype					1786:1792	the α1/β1 GABAA receptor subtype	1761:1792	the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity	1761:1892	From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
30028870	5	95	theme	well-behaving	825:837	arg1	assemblies					877:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	well-behaving and functional GABAA receptor subunit assemblies	825:886	Here, we describe a unique approach to screen for well-behaving and functional GABAA receptor subunit assemblies by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography (FSEC).
30028870	3	96	theme	basis	503:507	arg1	understanding					471:483	An understanding	468:483	An understanding of the structural basis of distinct receptor properties	468:539	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	9	97	dep	methods	1553:1559	arg1	improve					1564:1570	improve	1564:1570	to improve GABAA receptor expression in mammalian cell culture	1561:1622	Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction.
30028870	1	98	theme	receptor	144:151	arg1	family					153:158	the Cys-loop receptor family	131:158	the Cys-loop receptor family	131:158	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30028870	4	99	theme	Robust	644:649	arg1	expression					664:673	Robust heterologous expression	644:673	Robust heterologous expression	644:673	Robust heterologous expression and purification protocols of high expressing receptor constructs are vital for structural studies.
30028870	8	100	theme	expression	1511:1520	arg1	level					1522:1526	expression level	1511:1526	expression level	1511:1526	Mutagenesis experiments suggest that the α and β subunits can tolerate large truncations in the non-conserved M3/M4 cytoplasmic loop without compromising oligomeric assembly or GABA-gated channel activity, although removal of N-linked glycosylation sites is negatively correlated with expression level.
30028870	3	101	theme	properties	530:539	arg1	basis					503:507	the structural basis	488:507	the structural basis of distinct receptor properties	488:539	An understanding of the structural basis of distinct receptor properties has been hindered by the absence of high resolution structural information for heteromeric assemblies.
30028870	1	102	theme	inhibitory	231:240	arg1	neurotransmission					242:258	fast inhibitory neurotransmission	226:258	fast inhibitory neurotransmission	226:258	The GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system.
30032777	0	0	theme	selective	100:108	arg1	enrichment					110:119	selective enrichment	100:119	selective enrichment of glycopeptides	100:136	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	2	1	theme	MAR	367:369	arg1	MOP					371:373	The resulting MAR@MOP	353:373	The resulting MAR@MOP	353:373	The resulting MAR@MOP exhibited high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g).
30032777	7	2	theme	complicated	1308:1318	arg1	samples					1331:1337	complicated biological samples	1308:1337	complicated biological samples	1308:1337	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	2	3	theme	surface	399:405	arg1	area					407:410	high specific surface area	385:410	high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g)	385:480	The resulting MAR@MOP exhibited high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g).
30032777	6	4	gly	glycopeptides	1017:1029	arg2	glycopeptides					1017:1029	811 unique glycopeptides sequence	1006:1038	811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins	1006:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	2	5	theme	resulting	357:365	arg1	MOP					371:373	The resulting MAR@MOP	353:373	The resulting MAR@MOP	353:373	The resulting MAR@MOP exhibited high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g).
30032777	3	6	theme	MAR	620:622	arg1	surface					609:615	the surface	605:615	the surface of MAR	605:622	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	5	7	gly	glycopeptides	789:801	arg2	glycopeptides					789:801	glycopeptides	789:801	glycopeptides	789:801	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	4	8	theme	Fourier-transform	678:694	arg1	spectroscopy					705:716	Fourier-transform infrared spectroscopy	678:716	Fourier-transform infrared spectroscopy	678:716	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	5	9	theme	immunoglobulin	885:898	arg1	IgG					903:905	IgG	903:905	IgG	903:905	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	9	theme	immunoglobulin	885:898	arg1	G					900:900	human immunoglobulin G	879:900	human immunoglobulin G (IgG)	879:906	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	1	10	theme	microporous	282:292	arg1	MOP					312:314	MOP	312:314	MOP	312:314	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	1	10	theme	microporous	282:292	arg1	polymers					302:309	microporous organic polymers	282:309	microporous organic polymers (MOP)	282:315	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	7	11	from	enrichment	1235:1244	arg1	samples					1331:1337	complicated biological samples	1308:1337	complicated biological samples	1308:1337	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	6	12	from	sites	997:1001	arg1	sequence					1031:1038	811 unique glycopeptides sequence	1006:1038	811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins	1006:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	4	13	theme	MAR	653:655	arg1	MOP					657:659	MAR@MOP	653:659	MAR@MOP	653:659	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	7	14	theme	biological	1320:1329	arg1	samples					1331:1337	complicated biological samples	1308:1337	complicated biological samples	1308:1337	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	1	15	theme	organic	294:300	arg1	MOP					312:314	MOP	312:314	MOP	312:314	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	1	15	theme	organic	294:300	arg1	polymers					302:309	microporous organic polymers	282:309	microporous organic polymers (MOP)	282:315	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	6	16	theme	516 N-glycosylated	1050:1067	arg1	proteins					1069:1076	516 N-glycosylated proteins	1050:1076	516 N-glycosylated proteins	1050:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	7	17	gly	glycopeptides	1291:1303	arg2	glycopeptides					1291:1303	low-abundance N-linked glycopeptides	1268:1303	low-abundance N-linked glycopeptides	1268:1303	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	2	18	theme	131.3 m2/g	415:424	arg1	area					407:410	high specific surface area	385:410	high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g)	385:480	The resulting MAR@MOP exhibited high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g).
30032777	6	19	theme	unique	974:979	arg1	sites					997:1001	879 unique N-glycosylation sites	970:1001	879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins	970:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	1	20	theme	∼10 μm	181:186	arg1	diameter					188:195	∼10 μm diameter	181:195	∼10 μm diameter	181:195	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	0	21	theme	glycopeptides	124:136	arg1	enrichment					110:119	selective enrichment	100:119	selective enrichment of glycopeptides	100:136	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	1	22	with	resin	164:168	arg1	diameter					188:195	∼10 μm diameter	181:195	∼10 μm diameter	181:195	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	4	23	theme	infrared	696:703	arg1	spectroscopy					705:716	Fourier-transform infrared spectroscopy	678:716	Fourier-transform infrared spectroscopy	678:716	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	2	24	theme	specific	390:397	arg1	area					407:410	high specific surface area	385:410	high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g)	385:480	The resulting MAR@MOP exhibited high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g).
30032777	7	25	link	N-linked	1282:1289	arg1	glycopeptides					1291:1303	low-abundance N-linked glycopeptides	1268:1303	low-abundance N-linked glycopeptides	1268:1303	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	4	26	theme	MOP	657:659	arg1	composition					638:648	The chemical composition	625:648	The chemical composition of MAR@MOP	625:659	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	2	27	theme	high	385:388	arg1	area					407:410	high specific surface area	385:410	high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g)	385:480	The resulting MAR@MOP exhibited high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g).
30032777	0	28	theme	Facile	0:5	arg1	preparation					7:17	Facile preparation	0:17	Facile preparation of microporous organic polymers	0:49	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	1	29	theme	polymers	302:309	arg1	layer					273:277	a layer	271:277	a layer of microporous organic polymers (MOP)	271:315	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	5	30	theme	@	781:781	arg1	MOP					782:784	MAR@MOP	778:784	MAR@MOP	778:784	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	4	31	theme	@	656:656	arg1	MOP					657:659	MAR@MOP	653:659	MAR@MOP	653:659	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	0	32	theme	microporous	22:32	arg1	polymers					42:49	microporous organic polymers	22:49	microporous organic polymers	22:49	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	6	33	theme	N-glycosylation	981:995	arg1	sites					997:1001	879 unique N-glycosylation sites	970:1001	879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins	970:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	5	34	gly	glycopeptides	841:853	arg2	glycopeptides					841:853	N-linked glycopeptides	832:853	trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	823:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	34	gly	glycopeptides	841:853	arg1	digests					868:874	tryptic digests	860:874	tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	860:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	35	theme	bovine	942:947	arg1	fetuin					949:954	bovine fetuin	942:954	bovine fetuin	942:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	0	36	gly	glycopeptides	124:136	arg2	glycopeptides					124:136	glycopeptides	124:136	glycopeptides	124:136	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	5	37	theme	G	900:900	arg1	digests					868:874	tryptic digests	860:874	tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	860:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	38	dep	trapping	823:830	arg1	glycopeptides					841:853	N-linked glycopeptides	832:853	trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	823:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	1	39	mod	modified	257:264	arg1	MAR					171:173	MAR	171:173	MAR	171:173	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	1	39	mod	modified	257:264	arg1	resin					164:168	A macroporous adsorption resin	139:168	A macroporous adsorption resin (MAR) with ∼10 μm diameter	139:195	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	1	39	mod	modified	257:264	arg3	layer					273:277	a layer	271:277	a layer of microporous organic polymers (MOP)	271:315	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	3	40	theme	contact	487:493	arg1	angle					495:499	The contact angle	483:499	The contact angle	483:499	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	1	41	theme	seed-swelling	216:228	arg1	polymerization					230:243	seed-swelling polymerization	216:243	seed-swelling polymerization	216:243	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	0	42	theme	polymers	42:49	arg1	preparation					7:17	Facile preparation	0:17	Facile preparation of microporous organic polymers	0:49	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	4	43	theme	chemical	629:636	arg1	composition					638:648	The chemical composition	625:648	The chemical composition of MAR@MOP	625:659	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	3	44	theme	@	544:544	arg1	MOP					545:547	MAR@MOP	541:547	MAR@MOP	541:547	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	3	44	theme	@	544:544	arg1	24°					536:538	24°	536:538	24°	536:538	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	0	45	theme	organic	34:40	arg1	polymers					42:49	microporous organic polymers	22:49	microporous organic polymers	22:49	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	7	46	theme	N-linked	1282:1289	arg1	glycopeptides					1291:1303	low-abundance N-linked glycopeptides	1268:1303	low-abundance N-linked glycopeptides	1268:1303	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	4	47	theme	element	731:737	arg1	analysis					739:746	element analysis	731:746	element analysis	731:746	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	6	48	dep	analyses	1113:1120	arg1	replicate					1103:1111	replicate	1103:1111	replicate	1103:1111	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	5	49	theme	MAR	778:780	arg1	MOP					782:784	MAR@MOP	778:784	MAR@MOP	778:784	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	0	50	theme	macroporous	66:76	arg1	resin					90:94	macroporous hydrophilic resin	66:94	macroporous hydrophilic resin for selective enrichment of glycopeptides	66:136	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	6	51	gly	N-glycosylation	981:995	arg2	sites					997:1001	879 unique N-glycosylation sites	970:1001	879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins	970:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	6	51	gly	N-glycosylation	981:995	arg2	879					970:972	879	970:972	879	970:972	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	7	52	dep	enrichment	1235:1244	arg1	the					1231:1233	the	1231:1233	the	1231:1233	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	6	53	theme	glycopeptides	1017:1029	arg1	sequence					1031:1038	811 unique glycopeptides sequence	1006:1038	811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins	1006:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	5	54	theme	N-linked	832:839	arg1	glycopeptides					841:853	N-linked glycopeptides	832:853	trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	823:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	1	55	theme	one-pot	321:327	arg1	reaction					343:350	"one-pot" solvothermal reaction	320:350	"one-pot" solvothermal reaction	320:350	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	5	56	theme	fetuin	949:954	arg1	digests					868:874	tryptic digests	860:874	tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	860:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	3	57	theme	MAR	541:543	arg1	MOP					545:547	MAR@MOP	541:547	MAR@MOP	541:547	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	3	57	theme	MAR	541:543	arg1	24°					536:538	24°	536:538	24°	536:538	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	7	58	theme	glycopeptides	1291:1303	arg1	identification					1250:1263	identification	1250:1263	identification	1250:1263	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	7	58	theme	glycopeptides	1291:1303	arg1	enrichment					1235:1244	enrichment	1235:1244	enrichment	1235:1244	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	1	59	theme	macroporous	141:151	arg1	MAR					171:173	MAR	171:173	MAR	171:173	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	1	59	theme	macroporous	141:151	arg1	resin					164:168	A macroporous adsorption resin	139:168	A macroporous adsorption resin (MAR) with ∼10 μm diameter	139:195	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	1	60	theme	"	328:328	arg1	reaction					343:350	"one-pot" solvothermal reaction	320:350	"one-pot" solvothermal reaction	320:350	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	5	61	link	N-linked	832:839	arg1	glycopeptides					841:853	N-linked glycopeptides	832:853	trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	823:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	6	62	theme	mouse	1149:1153	arg1	liver					1155:1159	mouse liver	1149:1159	mouse liver	1149:1159	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	4	63	theme	13C	719:721	arg1	NMR					723:725	13C NMR	719:725	13C NMR	719:725	The chemical composition of MAR@MOP was confirmed by Fourier-transform infrared spectroscopy, 13C NMR and element analysis.
30032777	7	64	from	identification	1250:1263	arg1	samples					1331:1337	complicated biological samples	1308:1337	complicated biological samples	1308:1337	Therefore, this hydrophilic MOP-coated adsorbent would be applied in the enrichment and identification of low-abundance N-linked glycopeptides in complicated biological samples.
30032777	1	65	theme	adsorption	153:162	arg1	MAR					171:173	MAR	171:173	MAR	171:173	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	1	65	theme	adsorption	153:162	arg1	resin					164:168	A macroporous adsorption resin	139:168	A macroporous adsorption resin (MAR) with ∼10 μm diameter	139:195	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	5	66	theme	human	879:883	arg1	IgG					903:905	IgG	903:905	IgG	903:905	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	66	theme	human	879:883	arg1	G					900:900	human immunoglobulin G	879:900	human immunoglobulin G (IgG)	879:906	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	67	theme	horseradish	909:919	arg1	peroxidase					921:930	horseradish peroxidase	909:930	horseradish peroxidase (HRP)	909:936	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	67	theme	horseradish	909:919	arg1	HRP					933:935	HRP	933:935	HRP	933:935	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	68	theme	tryptic	860:866	arg1	digests					868:874	tryptic digests	860:874	tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	860:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	69	from	digests	868:874	arg1	glycopeptides					841:853	N-linked glycopeptides	832:853	trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	823:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	3	70	dep	58.8°	521:525	arg1	MOP					545:547	MAR@MOP	541:547	MAR@MOP	541:547	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	3	70	dep	58.8°	521:525	arg1	to					533:534	to	533:534	to	533:534	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	3	70	dep	58.8°	521:525	arg1	24°					536:538	24°	536:538	24°	536:538	The contact angle also decreased from 58.8° (MAR) to 24° (MAR@MOP), indicating that the MOP was successfully grafted onto the surface of MAR.
30032777	6	71	theme	unique	1010:1015	arg1	sequence					1031:1038	811 unique glycopeptides sequence	1006:1038	811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins	1006:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	5	72	theme	peroxidase	921:930	arg1	digests					868:874	tryptic digests	860:874	tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin	860:954	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	5	73	theme	enrichment	753:762	arg1	efficiency					764:773	The enrichment efficiency	749:773	The enrichment efficiency of MAR@MOP to glycopeptides	749:801	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	6	74	gly	516 N-glycosylated	1050:1067	arg1	proteins					1069:1076	516 N-glycosylated proteins	1050:1076	516 N-glycosylated proteins	1050:1076	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	5	75	theme	MOP	782:784	arg1	efficiency					764:773	The enrichment efficiency	749:773	The enrichment efficiency of MAR@MOP to glycopeptides	749:801	The enrichment efficiency of MAR@MOP to glycopeptides was demonstrated by trapping N-linked glycopeptides from tryptic digests of human immunoglobulin G (IgG), horseradish peroxidase (HRP) and bovine fetuin.
30032777	0	76	theme	hydrophilic	78:88	arg1	resin					90:94	macroporous hydrophilic resin	66:94	macroporous hydrophilic resin for selective enrichment of glycopeptides	66:136	Facile preparation of microporous organic polymers functionalized macroporous hydrophilic resin for selective enrichment of glycopeptides.
30032777	1	77	theme	solvothermal	330:341	arg1	reaction					343:350	"one-pot" solvothermal reaction	320:350	"one-pot" solvothermal reaction	320:350	A macroporous adsorption resin (MAR) with ∼10 μm diameter was synthesized by seed-swelling polymerization and further modified with a layer of microporous organic polymers (MOP) by "one-pot" solvothermal reaction.
30032777	6	78	theme	proteins	1125:1132	arg1	analyses					1113:1120	three replicate analyses	1097:1120	three replicate analyses of proteins extracted from mouse liver	1097:1159	Furthermore, 879 unique N-glycosylation sites in 811 unique glycopeptides sequence mapped to 516 N-glycosylated proteins were identified in three replicate analyses of proteins extracted from mouse liver.
30032777	2	79	theme	@	370:370	arg1	MOP					371:373	The resulting MAR@MOP	353:373	The resulting MAR@MOP	353:373	The resulting MAR@MOP exhibited high specific surface area of 131.3 m2/g, which was higher than that of pristine MAR (57.8 m2/g).
29687407	10	0	theme	non-brain	1891:1899	arg1	sequences					1901:1909	most non-brain sequences	1886:1909	most non-brain sequences	1886:1909	All brain sequences were predicted to use the CCR5 co-receptor, while most non-brain sequences were predicted to use CXCR4 co-receptor.
29687407	10	1	theme	most	1886:1889	arg1	sequences					1901:1909	most non-brain sequences	1886:1909	most non-brain sequences	1886:1909	All brain sequences were predicted to use the CCR5 co-receptor, while most non-brain sequences were predicted to use CXCR4 co-receptor.
29687407	0	2	theme	peripheral	198:207	arg1	tissues					209:215	immune and peripheral tissues	187:215	tissues	209:215	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	2	3	theme	long	619:622	arg1	sequence					624:631	long sequence	619:631	long sequence reads in a single run	619:653	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	13	4	theme	differential	2323:2334	arg1	pressure					2346:2353	differential selective pressure	2323:2353	differential selective pressure in the brain that may contribute to neurological disease	2323:2410	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	1	5	theme	neurological	294:305	arg1	disorders					307:315	neurological disorders	294:315	neurological disorders	294:315	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	6	6	theme	peripheral	1201:1210	arg1	tissues					1212:1218	all peripheral tissues	1197:1218	all peripheral tissues	1197:1218	Variants from all peripheral tissues were intermixed on the tree but independent of the brain clades.
29687407	3	7	theme	HIV	732:734	arg1	> 2200 bp					756:764	> 2200 bp	756:764	> 2200 bp	756:764	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	7	theme	HIV	732:734	arg1	sequences					745:753	~ 50,000 high-quality full-length HIV envelope sequences	698:753	~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites	698:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	4	8	theme	Sanger	870:875	arg1	sequencing					877:886	Sanger sequencing	870:886	Sanger sequencing	870:886	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	6	9	theme	brain	1271:1275	arg1	clades					1277:1282	the brain clades	1267:1282	the brain clades	1267:1282	Variants from all peripheral tissues were intermixed on the tree but independent of the brain clades.
29687407	9	10	theme	putative	1715:1722	arg1	N-sites					1754:1760	N-sites	1754:1760	N-sites	1754:1760	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	10	theme	putative	1715:1722	arg1	sites					1747:1751	putative N-linked glycosylation sites	1715:1751	putative N-linked glycosylation sites (N-sites)	1715:1761	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	10	theme	putative	1715:1722	arg1	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	4	11	dep	in	969:970	arg1	vitro					972:976	vitro	972:976	vitro	972:976	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	1	12	theme	antiretroviral	235:248	arg1	cART					259:262	cART	259:262	cART	259:262	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	1	12	theme	antiretroviral	235:248	arg1	therapy					250:256	combined antiretroviral therapy	226:256	combined antiretroviral therapy (cART)	226:263	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	9	13	theme	glycosylation	1733:1745	arg1	N-sites					1754:1760	N-sites	1754:1760	N-sites	1754:1760	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	13	theme	glycosylation	1733:1745	arg1	sites					1747:1751	putative N-linked glycosylation sites	1715:1751	putative N-linked glycosylation sites (N-sites)	1715:1761	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	13	theme	glycosylation	1733:1745	arg1	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	8	14	theme	brain	1422:1426	arg1	sequences					1428:1436	All brain sequences	1418:1436	All brain sequences	1418:1436	All brain sequences clustered exclusive of any non-brain sequences at all thresholds; however, frontal lobe sequences clustered independently of occipital and parietal lobes.
29687407	11	15	theme	Tropism	1952:1958	arg1	results					1960:1966	Tropism results	1952:1966	Tropism results	1952:1966	Tropism results were confirmed by in vitro infection assays.
29687407	13	16	theme	envelope	2291:2298	arg1	gene					2300:2303	the entire envelope gene	2280:2303	the entire envelope gene	2280:2303	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	12	17	theme	SMRT	2045:2048	arg1	approach					2061:2068	a SMRT sequencing approach	2043:2068	a SMRT sequencing approach	2043:2068	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	3	18	theme	autopsy	778:784	arg1	tissues					786:792	seven autopsy tissues	772:792	seven autopsy tissues	772:792	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	18	theme	autopsy	778:784	arg1	sites					863:867	four non-brain sites	848:867	four non-brain sites	848:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	18	theme	autopsy	778:784	arg1	brain					838:842	three brain	832:842	three brain	832:842	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	9	19	theme	non-brain	1676:1684	arg1	sequences					1686:1694	non-brain sequences	1676:1694	non-brain sequences	1676:1694	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	0	20	theme	immune	187:192	arg1	tissues					209:215	immune and peripheral tissues	187:215	tissues	209:215	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	10	21	theme	brain	1820:1824	arg1	sequences					1826:1834	All brain sequences	1816:1834	All brain sequences	1816:1834	All brain sequences were predicted to use the CCR5 co-receptor, while most non-brain sequences were predicted to use CXCR4 co-receptor.
29687407	3	22	theme	non-brain	853:861	arg1	sites					863:867	four non-brain sites	848:867	four non-brain sites	848:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	9	23	theme	V1	1764:1765	arg1	length					1767:1772	V1 length	1764:1772	V1 length	1764:1772	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	8	24	theme	non-brain	1465:1473	arg1	sequences					1475:1483	any non-brain sequences	1461:1483	any non-brain sequences	1461:1483	All brain sequences clustered exclusive of any non-brain sequences at all thresholds; however, frontal lobe sequences clustered independently of occipital and parietal lobes.
29687407	7	25	theme	similarity	1354:1363	arg1	thresholds					1365:1374	three similarity thresholds	1348:1374	three similarity thresholds (99, 99.5, and 99.9%)	1348:1396	Due to the large number of sequences, a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%) was also performed.
29687407	7	25	theme	similarity	1354:1363	arg1	%					1395:1395	99, 99.5, and 99.9%	1377:1395	99, 99.5, and 99.9%	1377:1395	Due to the large number of sequences, a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%) was also performed.
29687407	3	26	theme	HIV+/cART+	802:811	arg1	subject					813:819	an HIV+/cART+ subject	799:819	an HIV+/cART+ subject	799:819	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	0	27	theme	complete	71:78	arg1	compartmentalization					80:99	complete compartmentalization	71:99	complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues	71:215	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	1	28	theme	HIV	349:351	arg1	infection					353:361	persistent HIV infection	338:361	persistent HIV infection	338:361	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	0	29	theme	real-time	26:34	arg1	sequencing					36:45	Ultradeep single-molecule real-time sequencing	0:45	Ultradeep single-molecule real-time sequencing of HIV envelope	0:61	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	13	30	theme	sequence	2232:2239	arg1	length					2241:2246	the long sequence length	2223:2246	the long sequence length	2223:2246	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	2	31	theme	HIV	523:525	arg1	isolates					527:534	HIV isolates	523:534	HIV isolates	523:534	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	2	32	theme	lymphoid	553:560	arg1	tissues					562:568	lymphoid tissues	553:568	lymphoid tissues	553:568	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	0	33	theme	macrophage-tropic	111:127	arg1	variants					141:148	highly macrophage-tropic R5 proviral variants	104:148	highly macrophage-tropic R5 proviral variants	104:148	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	9	34	from	differences	1646:1656	arg1	location					1703:1710	the location	1699:1710	the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites	1699:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	13	35	from	pressure	2346:2353	arg1	brain					2362:2366	the brain	2358:2366	the brain that may contribute to neurological disease	2358:2410	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	0	36	theme	proviral	132:139	arg1	variants					141:148	highly macrophage-tropic R5 proviral variants	104:148	highly macrophage-tropic R5 proviral variants	104:148	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	1	37	theme	brain	390:394	arg1	tissues					396:402	brain tissues	390:402	brain tissues	390:402	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	12	38	from	compartmentalization	2083:2102	arg1	tissues					2107:2113	tissues	2107:2113	tissues	2107:2113	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	5	39	theme	Phylogenetic	994:1005	arg1	analysis					1007:1014	Phylogenetic analysis	994:1014	Phylogenetic analysis	994:1014	Phylogenetic analysis demonstrated that brain-derived HIV was compartmentalized from HIV outside the brain and that the variants from each of the three brain tissues grouped independently.
29687407	9	40	theme	number	1794:1799	arg1	location					1703:1710	the location	1699:1710	the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites	1699:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	8	41	theme	frontal	1513:1519	arg1	sequences					1526:1534	frontal lobe sequences	1513:1534	frontal lobe sequences	1513:1534	All brain sequences clustered exclusive of any non-brain sequences at all thresholds; however, frontal lobe sequences clustered independently of occipital and parietal lobes.
29687407	6	42	from	tissues	1212:1218	arg1	Variants					1183:1190	Variants	1183:1190	Variants from all peripheral tissues	1183:1218	Variants from all peripheral tissues were intermixed on the tree but independent of the brain clades.
29687407	2	43	theme	Single-molecule	405:419	arg1	SMRT					432:435	SMRT	432:435	SMRT	432:435	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	2	43	theme	Single-molecule	405:419	arg1	technology					449:458	Single-molecule real-time (SMRT) sequencing technology	405:458	Single-molecule real-time (SMRT) sequencing technology	405:458	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	0	44	theme	Ultradeep	0:8	arg1	sequencing					36:45	Ultradeep single-molecule real-time sequencing	0:45	Ultradeep single-molecule real-time sequencing of HIV envelope	0:61	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	4	45	used	used	892:895	arg2	sequencing					877:886	Sanger sequencing	870:886	Sanger sequencing	870:886	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	9	46	theme	V4	1804:1805	arg1	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	5	47	from	each	1128:1131	arg1	variants					1114:1121	the variants	1110:1121	the variants from each of the three brain tissues	1110:1158	Phylogenetic analysis demonstrated that brain-derived HIV was compartmentalized from HIV outside the brain and that the variants from each of the three brain tissues grouped independently.
29687407	13	48	theme	neurological	2391:2402	arg1	disease					2404:2410	neurological disease	2391:2410	neurological disease	2391:2410	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	9	49	theme	Translated	1593:1602	arg1	sequences					1604:1612	Translated sequences	1593:1612	Translated sequences	1593:1612	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	7	50	theme	sequences	1312:1320	arg1	number					1302:1307	the large number	1292:1307	the large number of sequences	1292:1320	Due to the large number of sequences, a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%) was also performed.
29687407	8	51	theme	occipital	1563:1571	arg1	lobes					1586:1590	occipital and parietal lobes	1563:1590	occipital and parietal lobes	1563:1590	All brain sequences clustered exclusive of any non-brain sequences at all thresholds; however, frontal lobe sequences clustered independently of occipital and parietal lobes.
29687407	9	52	theme	length	1767:1772	arg1	location					1703:1710	the location	1699:1710	the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites	1699:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	1	53	from	infection	353:361	arg1	tissues					396:402	brain tissues	390:402	brain tissues	390:402	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	8	54	theme	parietal	1577:1584	arg1	lobes					1586:1590	occipital and parietal lobes	1563:1590	occipital and parietal lobes	1563:1590	All brain sequences clustered exclusive of any non-brain sequences at all thresholds; however, frontal lobe sequences clustered independently of occipital and parietal lobes.
29687407	9	55	theme	functional	1635:1644	arg1	differences					1646:1656	potentially functional differences	1623:1656	potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites	1623:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	3	56	theme	SMRT	670:673	arg1	sequencing					675:684	SMRT sequencing	670:684	SMRT sequencing	670:684	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	12	57	theme	limited	2145:2151	arg1	trafficking					2153:2163	limited trafficking	2145:2163	limited trafficking between brain and non-brain sequences during cART	2145:2213	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	5	58	theme	brain-derived	1034:1046	arg1	HIV					1048:1050	brain-derived HIV	1034:1050	brain-derived HIV	1034:1050	Phylogenetic analysis demonstrated that brain-derived HIV was compartmentalized from HIV outside the brain and that the variants from each of the three brain tissues grouped independently.
29687407	3	59	used	used	665:668	arg2	we					662:663	we	662:663	we	662:663	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	60	theme	full-length	720:730	arg1	> 2200 bp					756:764	> 2200 bp	756:764	> 2200 bp	756:764	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	60	theme	full-length	720:730	arg1	sequences					745:753	~ 50,000 high-quality full-length HIV envelope sequences	698:753	~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites	698:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	2	61	theme	sequence	624:631	arg1	thousands					606:614	thousands	606:614	thousands of long sequence reads in a single run	606:653	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	9	62	link	N-linked	1724:1731	arg1	N-sites					1754:1760	N-sites	1754:1760	N-sites	1754:1760	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	62	link	N-linked	1724:1731	arg1	sites					1747:1751	putative N-linked glycosylation sites	1715:1751	putative N-linked glycosylation sites (N-sites)	1715:1761	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	62	link	N-linked	1724:1731	arg1	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	11	63	theme	infection	1995:2003	arg1	assays					2005:2010	in vitro infection assays	1986:2010	in vitro infection assays	1986:2010	Tropism results were confirmed by in vitro infection assays.
29687407	0	64	from	variants	175:182	arg1	tissues					209:215	immune and peripheral tissues	187:215	tissues	209:215	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	11	65	theme	in	1986:1987	arg1	assays					2005:2010	in vitro infection assays	1986:2010	in vitro infection assays	1986:2010	Tropism results were confirmed by in vitro infection assays.
29687407	0	66	theme	envelope	54:61	arg1	sequencing					36:45	Ultradeep single-molecule real-time sequencing	0:45	Ultradeep single-molecule real-time sequencing of HIV envelope	0:61	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	2	67	theme	single	644:649	arg1	run					651:653	a single run	642:653	a single run	642:653	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	3	68	theme	envelope	736:743	arg1	> 2200 bp					756:764	> 2200 bp	756:764	> 2200 bp	756:764	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	68	theme	envelope	736:743	arg1	sequences					745:753	~ 50,000 high-quality full-length HIV envelope sequences	698:753	~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites	698:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	6	69	theme	clades	1277:1282	arg1	independent					1252:1262	independent	1252:1262	independent	1252:1262	Variants from all peripheral tissues were intermixed on the tree but independent of the brain clades.
29687407	9	70	gly	glycosylation	1733:1745	arg2	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	70	gly	glycosylation	1733:1745	arg2	N-sites					1754:1760	N-sites	1754:1760	N-sites	1754:1760	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	70	gly	glycosylation	1733:1745	arg1	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	70	gly	glycosylation	1733:1745	arg2	sites					1747:1751	putative N-linked glycosylation sites	1715:1751	putative N-linked glycosylation sites (N-sites)	1715:1761	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	5	71	link	brain-derived	1034:1046	arg1	HIV					1048:1050	brain-derived HIV	1034:1050	brain-derived HIV	1034:1050	Phylogenetic analysis demonstrated that brain-derived HIV was compartmentalized from HIV outside the brain and that the variants from each of the three brain tissues grouped independently.
29687407	1	72	theme	combined	226:233	arg1	cART					259:262	cART	259:262	cART	259:262	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	1	72	theme	combined	226:233	arg1	therapy					250:256	combined antiretroviral therapy	226:256	combined antiretroviral therapy (cART)	226:263	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	9	73	theme	N-linked	1724:1731	arg1	N-sites					1754:1760	N-sites	1754:1760	N-sites	1754:1760	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	73	theme	N-linked	1724:1731	arg1	sites					1747:1751	putative N-linked glycosylation sites	1715:1751	putative N-linked glycosylation sites (N-sites)	1715:1761	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	73	theme	N-linked	1724:1731	arg1	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	10	74	theme	CXCR4	1933:1937	arg1	co-receptor					1939:1949	CXCR4 co-receptor	1933:1949	CXCR4 co-receptor	1933:1949	All brain sequences were predicted to use the CCR5 co-receptor, while most non-brain sequences were predicted to use CXCR4 co-receptor.
29687407	0	75	theme	CXCR4-using	163:173	arg1	variants					175:182	CXCR4-using variants	163:182	CXCR4-using variants	163:182	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	13	76	theme	entire	2284:2289	arg1	gene					2300:2303	the entire envelope gene	2280:2303	the entire envelope gene	2280:2303	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	4	77	theme	clone	934:938	arg1	pseudoviruses					951:963	clone functional pseudoviruses	934:963	clone functional pseudoviruses	934:963	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	0	78	from	compartmentalization	80:99	arg1	brain					153:157	brain	153:157	brain	153:157	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	0	78	from	compartmentalization	80:99	arg1	variants					175:182	CXCR4-using variants	163:182	CXCR4-using variants	163:182	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	12	79	theme	HIV	2079:2081	arg1	compartmentalization					2083:2102	HIV compartmentalization	2079:2102	HIV compartmentalization in tissues	2079:2113	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	9	80	theme	charge	1778:1783	arg1	location					1703:1710	the location	1699:1710	the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites	1699:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	11	81	dep	in	1986:1987	arg1	vitro					1989:1993	vitro	1989:1993	vitro	1989:1993	Tropism results were confirmed by in vitro infection assays.
29687407	2	82	dep	sequence	624:631	arg1	reads					633:637	reads	633:637	reads in a single run	633:653	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	4	83	theme	SMRT	917:920	arg1	data					922:925	SMRT data	917:925	SMRT data	917:925	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	8	84	theme	sequences	1475:1483	arg1	exclusive					1448:1456	exclusive	1448:1456	exclusive	1448:1456	All brain sequences clustered exclusive of any non-brain sequences at all thresholds; however, frontal lobe sequences clustered independently of occipital and parietal lobes.
29687407	12	85	theme	sequencing	2050:2059	arg1	approach					2061:2068	a SMRT sequencing approach	2043:2068	a SMRT sequencing approach	2043:2068	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	4	86	dep	data	922:925	arg1	pseudoviruses					951:963	clone functional pseudoviruses	934:963	clone functional pseudoviruses	934:963	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	13	87	theme	long	2227:2230	arg1	length					2241:2246	the long sequence length	2223:2246	the long sequence length	2223:2246	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	4	88	theme	tropism	978:984	arg1	assays					986:991	in vitro tropism assays	969:991	in vitro tropism assays	969:991	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	5	89	theme	brain	1146:1150	arg1	tissues					1152:1158	the three brain tissues	1136:1158	the three brain tissues	1136:1158	Phylogenetic analysis demonstrated that brain-derived HIV was compartmentalized from HIV outside the brain and that the variants from each of the three brain tissues grouped independently.
29687407	9	90	theme	V3	1775:1776	arg1	charge					1778:1783	V3 charge	1775:1783	V3 charge	1775:1783	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	3	91	from	tissues	786:792	arg1	> 2200 bp					756:764	> 2200 bp	756:764	> 2200 bp	756:764	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	91	from	tissues	786:792	arg1	sequences					745:753	~ 50,000 high-quality full-length HIV envelope sequences	698:753	~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites	698:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	0	92	theme	R5	129:130	arg1	variants					141:148	highly macrophage-tropic R5 proviral variants	104:148	highly macrophage-tropic R5 proviral variants	104:148	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	1	93	theme	selective	367:375	arg1	evolution					377:385	selective evolution	367:385	selective evolution	367:385	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	0	94	theme	variants	141:148	arg1	compartmentalization					80:99	complete compartmentalization	71:99	complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues	71:215	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	12	95	dep	first	2030:2034	arg1	use					2039:2041	use	2039:2041	to use a SMRT sequencing approach to study HIV compartmentalization in tissues	2036:2113	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	12	95	dep	first	2030:2034	arg1	study					2017:2021	The study	2013:2021	The study	2013:2021	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	12	95	dep	first	2030:2034	arg1	first					2030:2034	first	2030:2034	first	2030:2034	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	12	95	dep	first	2030:2034	arg1	supports					2119:2126	supports	2119:2126	supports other reports of limited trafficking between brain and non-brain sequences during cART	2119:2213	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	7	96	from	thresholds	1365:1374	arg1	analysis					1336:1343	a clustering analysis	1323:1343	a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%)	1323:1396	Due to the large number of sequences, a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%) was also performed.
29687407	4	97	theme	in	969:970	arg1	assays					986:991	in vitro tropism assays	969:991	in vitro tropism assays	969:991	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	2	98	from	relationship	504:515	arg1	brain					543:547	brain	543:547	brain	543:547	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	2	98	from	relationship	504:515	arg1	tissues					562:568	lymphoid tissues	553:568	lymphoid tissues	553:568	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	4	99	theme	functional	940:949	arg1	pseudoviruses					951:963	clone functional pseudoviruses	934:963	clone functional pseudoviruses	934:963	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	2	100	theme	real-time	421:429	arg1	SMRT					432:435	SMRT	432:435	SMRT	432:435	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	2	100	theme	real-time	421:429	arg1	technology					449:458	Single-molecule real-time (SMRT) sequencing technology	405:458	Single-molecule real-time (SMRT) sequencing technology	405:458	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	0	101	theme	single-molecule	10:24	arg1	sequencing					36:45	Ultradeep single-molecule real-time sequencing	0:45	Ultradeep single-molecule real-time sequencing of HIV envelope	0:61	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	7	102	theme	clustering	1325:1334	arg1	analysis					1336:1343	a clustering analysis	1323:1343	a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%)	1323:1396	Due to the large number of sequences, a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%) was also performed.
29687407	2	103	theme	improved	470:477	arg1	opportunity					479:489	an improved opportunity	467:489	an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run	467:653	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	12	104	theme	non-brain	2183:2191	arg1	sequences					2193:2201	non-brain sequences	2183:2201	non-brain sequences	2183:2201	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	1	105	from	evolution	377:385	arg1	tissues					396:402	brain tissues	390:402	brain tissues	390:402	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	2	106	dep	brain	543:547	arg1	the					539:541	the	539:541	the	539:541	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	9	107	theme	N-sites	1807:1813	arg1	N-sites					1754:1760	N-sites	1754:1760	N-sites	1754:1760	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	107	theme	N-sites	1807:1813	arg1	N-sites					1807:1813	V4 N-sites	1804:1813	V4 N-sites	1804:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	107	theme	N-sites	1807:1813	arg1	charge					1778:1783	V3 charge	1775:1783	V3 charge	1775:1783	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	107	theme	N-sites	1807:1813	arg1	sites					1747:1751	putative N-linked glycosylation sites	1715:1751	putative N-linked glycosylation sites (N-sites)	1715:1761	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	107	theme	N-sites	1807:1813	arg1	length					1767:1772	V1 length	1764:1772	V1 length	1764:1772	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	9	107	theme	N-sites	1807:1813	arg1	number					1794:1799	the number	1790:1799	the number of V4 N-sites	1790:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	2	108	theme	sequencing	438:447	arg1	SMRT					432:435	SMRT	432:435	SMRT	432:435	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	2	108	theme	sequencing	438:447	arg1	technology					449:458	Single-molecule real-time (SMRT) sequencing technology	405:458	Single-molecule real-time (SMRT) sequencing technology	405:458	Single-molecule real-time (SMRT) sequencing technology offers an improved opportunity to study the relationship among HIV isolates in the brain and lymphoid tissues because it is capable of generating thousands of long sequence reads in a single run.
29687407	0	109	theme	HIV	50:52	arg1	envelope					54:61	HIV envelope	50:61	HIV envelope	50:61	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	4	110	with	comparison	901:910	arg1	to					931:932	to	931:932	to	931:932	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	4	110	with	comparison	901:910	arg1	data					922:925	SMRT data	917:925	SMRT data	917:925	Sanger sequencing was used for comparison with SMRT data and to clone functional pseudoviruses for in vitro tropism assays.
29687407	12	111	theme	trafficking	2153:2163	arg1	reports					2134:2140	other reports	2128:2140	other reports of limited trafficking between brain and non-brain sequences during cART	2128:2213	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	8	112	theme	lobe	1521:1524	arg1	sequences					1526:1534	frontal lobe sequences	1513:1534	frontal lobe sequences	1513:1534	All brain sequences clustered exclusive of any non-brain sequences at all thresholds; however, frontal lobe sequences clustered independently of occipital and parietal lobes.
29687407	7	113	theme	large	1296:1300	arg1	number					1302:1307	the large number	1292:1307	the large number of sequences	1292:1320	Due to the large number of sequences, a clustering analysis at three similarity thresholds (99, 99.5, and 99.9%) was also performed.
29687407	9	114	theme	sites	1747:1751	arg1	location					1703:1710	the location	1699:1710	the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites	1699:1813	Translated sequences revealed potentially functional differences between brain and non-brain sequences in the location of putative N-linked glycosylation sites (N-sites), V1 length, V3 charge, and the number of V4 N-sites.
29687407	3	115	from	subject	813:819	arg1	tissues					786:792	seven autopsy tissues	772:792	seven autopsy tissues	772:792	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	115	from	subject	813:819	arg1	sites					863:867	four non-brain sites	848:867	four non-brain sites	848:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	115	from	subject	813:819	arg1	brain					838:842	three brain	832:842	three brain	832:842	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	1	116	theme	persistent	338:347	arg1	infection					353:361	persistent HIV infection	338:361	persistent HIV infection	338:361	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
29687407	10	117	theme	CCR5	1862:1865	arg1	co-receptor					1867:1877	the CCR5 co-receptor	1858:1877	the CCR5 co-receptor	1858:1877	All brain sequences were predicted to use the CCR5 co-receptor, while most non-brain sequences were predicted to use CXCR4 co-receptor.
29687407	12	118	theme	other	2128:2132	arg1	reports					2134:2140	other reports	2128:2140	other reports of limited trafficking between brain and non-brain sequences during cART	2128:2213	The study is the first to use a SMRT sequencing approach to study HIV compartmentalization in tissues and supports other reports of limited trafficking between brain and non-brain sequences during cART.
29687407	13	119	theme	selective	2336:2344	arg1	pressure					2346:2353	differential selective pressure	2323:2353	differential selective pressure in the brain that may contribute to neurological disease	2323:2410	Due to the long sequence length, we could observe changes along the entire envelope gene, likely caused by differential selective pressure in the brain that may contribute to neurological disease.
29687407	0	120	from	brain	153:157	arg1	tissues					209:215	immune and peripheral tissues	187:215	tissues	209:215	Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues.
29687407	3	121	theme	high-quality	707:718	arg1	> 2200 bp					756:764	> 2200 bp	756:764	> 2200 bp	756:764	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	3	121	theme	high-quality	707:718	arg1	sequences					745:753	~ 50,000 high-quality full-length HIV envelope sequences	698:753	~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites	698:867	Here, we used SMRT sequencing to generate ~ 50,000 high-quality full-length HIV envelope sequences (> 2200 bp) from seven autopsy tissues from an HIV+/cART+ subject, including three brain and four non-brain sites.
29687407	1	122	theme	HIV+	266:269	arg1	patients					271:278	HIV+ patients	266:278	HIV+ patients	266:278	Despite combined antiretroviral therapy (cART), HIV+ patients still develop neurological disorders, which may be due to persistent HIV infection and selective evolution in brain tissues.
27343203	7	0	from	binding	1341:1347	arg1	RESULTS					1183:1189	RESULTS	1183:1189	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.	1183:1380	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	7	0	from	binding	1341:1347	arg1	superior					1325:1332	superior	1325:1332	superior	1325:1332	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	7	0	from	binding	1341:1347	arg1	version					1305:1311	the non-N-glycosylated monomeric version	1272:1311	the non-N-glycosylated monomeric version of CD23	1272:1319	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	7	1	theme	non-N-glycosylated	1276:1293	arg1	superior					1325:1332	superior	1325:1332	superior	1325:1332	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	7	1	theme	non-N-glycosylated	1276:1293	arg1	version					1305:1311	the non-N-glycosylated monomeric version	1272:1311	the non-N-glycosylated monomeric version of CD23	1272:1319	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	2	2	dep	allergen	430:437	arg1	v					443:443	Bet v 1	439:445	the corresponding birch pollen allergen Bet v 1	399:445	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	10	3	theme	antibody	1751:1758	arg1	omalizumab					1760:1769	the therapeutic anti-IgE antibody omalizumab	1726:1769	the therapeutic anti-IgE antibody omalizumab	1726:1769	We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
27343203	0	4	theme	IgE	60:62	arg1	binding					64:70	IgE binding	60:70	IgE binding	60:70	Critical and direct involvement of the CD23 stalk region in IgE binding.
27343203	4	5	theme	head	776:779	arg1	domain					781:786	the head domain	772:786	the head domain	772:786	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	4	5	theme	head	776:779	arg1	complete					791:798	complete	791:798	complete	791:798	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	4	5	theme	head	776:779	arg1	truncated					806:814	truncated	806:814	truncated	806:814	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	7	6	theme	IgE	1337:1339	arg1	binding					1341:1347	IgE binding	1337:1347	IgE binding	1337:1347	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	6	7	theme	stain	1141:1145	arg1	microscopy					1156:1165	negative stain electron microscopy	1132:1165	negative stain electron microscopy	1132:1165	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	10	8	theme	anti-IgE	1742:1749	arg1	omalizumab					1760:1769	the therapeutic anti-IgE antibody omalizumab	1726:1769	the therapeutic anti-IgE antibody omalizumab	1726:1769	We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
27343203	5	9	theme	monomeric	854:862	arg1	proteins					888:895	monomeric and structurally folded proteins	854:895	monomeric and structurally folded proteins	854:895	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	5	9	theme	monomeric	854:862	arg1	variants					828:835	The 4 CD23 variants	817:835	The 4 CD23 variants	817:835	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	7	10	theme	CD23	1262:1265	arg1	region					1252:1257	the stalk region	1242:1257	the stalk region of CD23	1242:1265	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	1	11	theme	IgE	228:230	arg1	responses					232:240	IgE responses	228:240	IgE responses	228:240	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	10	12	theme	CD23	1641:1644	arg1	region					1631:1636	the stalk region	1621:1636	the stalk region of CD23	1621:1644	We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
27343203	6	13	theme	negative	1132:1139	arg1	microscopy					1156:1165	negative stain electron microscopy	1132:1165	negative stain electron microscopy	1132:1165	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	3	14	theme	CD23	493:496	arg1	variants					498:505	4 CD23 variants	491:505	4 CD23 variants	491:505	METHODS: We expressed 4 CD23 variants.
27343203	10	15	theme	therapeutic	1730:1740	arg1	omalizumab					1760:1769	the therapeutic anti-IgE antibody omalizumab	1726:1769	the therapeutic anti-IgE antibody omalizumab	1726:1769	We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
27343203	1	16	theme	responses	232:240	arg1	enhancement					247:257	enhancement	247:257	enhancement of transepithelial allergen migration	247:295	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	1	16	theme	responses	232:240	arg1	presentation					189:200	allergen presentation	180:200	allergen presentation to T cells	180:211	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	1	16	theme	responses	232:240	arg1	regulation					214:223	regulation	214:223	regulation of IgE responses	214:240	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	7	17	gly	non-N-glycosylated	1276:1293	arg1	superior					1325:1332	superior	1325:1332	superior	1325:1332	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	7	17	gly	non-N-glycosylated	1276:1293	arg1	version					1305:1311	the non-N-glycosylated monomeric version	1272:1311	the non-N-glycosylated monomeric version of CD23	1272:1319	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	4	18	with	identical	621:629	arg1	first					640:644	first	640:644	first	640:644	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	4	19	from	exchange	672:679	arg1	region					694:699	the stalk region	684:699	the stalk region abolishing the N-linked glycosylation site	684:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	4	20	theme	stalk	688:692	arg1	region					694:699	the stalk region	684:699	the stalk region abolishing the N-linked glycosylation site	684:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	2	21	theme	chimeric	364:371	arg1	IgE					390:392	chimeric monoclonal human IgE	364:392	chimeric monoclonal human IgE	364:392	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	0	22	theme	CD23	39:42	arg1	region					50:55	the CD23 stalk region	35:55	the CD23 stalk region	35:55	Critical and direct involvement of the CD23 stalk region in IgE binding.
27343203	6	23	theme	IgE	973:975	arg1	mAb					977:979	a human IgE mAb	965:979	a human IgE mAb	965:979	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	23	theme	IgE	973:975	arg1	v					1013:1013	the corresponding allergen Bet v 1	982:1015	the corresponding allergen Bet v 1	982:1015	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	2	24	theme	corresponding	403:415	arg1	allergen					430:437	the corresponding birch pollen allergen	399:437	the corresponding birch pollen allergen Bet v 1	399:445	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	4	25	theme	head	594:597	arg1	domain					599:604	the stalk and head domain	580:604	domain	599:604	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	2	26	theme	birch	417:421	arg1	allergen					430:437	the corresponding birch pollen allergen	399:437	the corresponding birch pollen allergen Bet v 1	399:445	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	7	27	theme	CD23	1316:1319	arg1	superior					1325:1332	superior	1325:1332	superior	1325:1332	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	7	27	theme	CD23	1316:1319	arg1	version					1305:1311	the non-N-glycosylated monomeric version	1272:1311	the non-N-glycosylated monomeric version of CD23	1272:1319	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	6	28	theme	inhibition	1110:1119	arg1	assays					1121:1126	both binding and inhibition assays	1093:1126	assays	1121:1126	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	9	29	theme	CD23-IgE	1586:1593	arg1	interaction					1595:1605	the CD23-IgE interaction	1582:1605	the CD23-IgE interaction	1582:1605	CONCLUSION: Our results provide a new model for the CD23-IgE interaction.
27343203	10	30	theme	stalk	1625:1629	arg1	region					1631:1636	the stalk region	1621:1636	the stalk region of CD23	1621:1644	We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
27343203	8	31	theme	IgE	1476:1478	arg1	binding					1480:1486	IgE binding	1476:1486	IgE binding to FcεRI	1476:1495	Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.
27343203	0	32	theme	Critical	0:7	arg1	involvement					20:30	Critical and direct involvement	0:30	Critical and direct involvement of the CD23 stalk region in IgE binding.	0:71	Critical and direct involvement of the CD23 stalk region in IgE binding.
27343203	7	33	theme	glycosylated	1363:1374	arg1	CD23					1376:1379	glycosylated CD23	1363:1379	glycosylated CD23	1363:1379	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	5	34	theme	circular	936:943	arg1	dichroism					945:953	circular dichroism	936:953	circular dichroism	936:953	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	6	35	theme	electron	1147:1154	arg1	microscopy					1156:1165	negative stain electron microscopy	1132:1165	negative stain electron microscopy	1132:1165	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	7	36	theme	IgE-binding	1211:1221	arg1	site					1223:1226	A hitherto unknown IgE-binding site	1192:1226	A hitherto unknown IgE-binding site	1192:1226	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	4	37	theme	acid	667:670	arg1	exchange					672:679	an amino acid exchange	658:679	an amino acid exchange in the stalk region abolishing the N-linked glycosylation site	658:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	7	38	theme	stalk	1246:1250	arg1	region					1252:1257	the stalk region	1242:1257	the stalk region of CD23	1242:1265	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	1	39	theme	allergic	150:157	arg1	inflammation					159:170	allergic inflammation	150:170	allergic inflammation	150:170	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	0	40	theme	direct	13:18	arg1	involvement					20:30	Critical and direct involvement	0:30	Critical and direct involvement of the CD23 stalk region in IgE binding.	0:71	Critical and direct involvement of the CD23 stalk region in IgE binding.
27343203	8	41	theme	anti-IgE	1430:1437	arg1	omalizumab					1449:1458	omalizumab	1449:1458	omalizumab	1449:1458	Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.
27343203	8	41	theme	anti-IgE	1430:1437	arg1	antibody					1439:1446	a therapeutic anti-IgE antibody	1416:1446	a therapeutic anti-IgE antibody	1416:1446	Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.
27343203	6	42	theme	antibodies	1033:1042	arg1	mAb					977:979	a human IgE mAb	965:979	a human IgE mAb	965:979	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	42	theme	antibodies	1033:1042	arg1	panel					1024:1028	a panel	1022:1028	a panel of antibodies specific for peptides spanning the CD23 surface	1022:1090	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	42	theme	antibodies	1033:1042	arg1	v					1013:1013	the corresponding allergen Bet v 1	982:1015	the corresponding allergen Bet v 1	982:1015	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	4	43	theme	amino	661:665	arg1	exchange					672:679	an amino acid exchange	658:679	an amino acid exchange in the stalk region abolishing the N-linked glycosylation site	658:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	8	44	theme	therapeutic	1418:1428	arg1	omalizumab					1449:1458	omalizumab	1449:1458	omalizumab	1449:1458	Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.
27343203	8	44	theme	therapeutic	1418:1428	arg1	antibody					1439:1446	a therapeutic anti-IgE antibody	1416:1446	a therapeutic anti-IgE antibody	1416:1446	Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.
27343203	4	45	theme	stalk	584:588	arg1	domain					599:604	the stalk and head domain	580:604	domain	599:604	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	2	46	theme	human	384:388	arg1	IgE					390:392	chimeric monoclonal human IgE	364:392	chimeric monoclonal human IgE	364:392	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	2	47	theme	Bet	439:441	arg1	v					443:443	Bet v 1	439:445	the corresponding birch pollen allergen Bet v 1	399:445	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	1	48	theme	transepithelial	262:276	arg1	migration					287:295	transepithelial allergen migration	262:295	transepithelial allergen migration	262:295	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	6	49	theme	specific	1044:1051	arg1	antibodies					1033:1042	antibodies	1033:1042	antibodies specific for peptides spanning the CD23 surface	1033:1090	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	4	50	theme	glycosylation	725:737	arg1	site					739:742	the N-linked glycosylation site	712:742	the N-linked glycosylation site	712:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	2	51	theme	monoclonal	373:382	arg1	IgE					390:392	chimeric monoclonal human IgE	364:392	chimeric monoclonal human IgE	364:392	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	0	52	theme	stalk	44:48	arg1	region					50:55	the CD23 stalk region	35:55	the CD23 stalk region	35:55	Critical and direct involvement of the CD23 stalk region in IgE binding.
27343203	1	53	theme	allergen	278:285	arg1	migration					287:295	transepithelial allergen migration	262:295	transepithelial allergen migration	262:295	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	9	54	theme	new	1568:1570	arg1	model					1572:1576	a new model	1566:1576	a new model for the CD23-IgE interaction	1566:1605	CONCLUSION: Our results provide a new model for the CD23-IgE interaction.
27343203	1	55	theme	low-affinity	89:100	arg1	FcεRII					120:125	FcεRII	120:125	FcεRII (CD23)	120:132	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	1	55	theme	low-affinity	89:100	arg1	receptor					102:109	The low-affinity receptor	85:109	The low-affinity receptor for IgE	85:117	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	2	56	theme	pollen	423:428	arg1	allergen					430:437	the corresponding birch pollen allergen	399:437	the corresponding birch pollen allergen Bet v 1	399:445	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	1	57	theme	migration	287:295	arg1	enhancement					247:257	enhancement	247:257	enhancement of transepithelial allergen migration	247:295	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	1	57	theme	migration	287:295	arg1	presentation					189:200	allergen presentation	180:200	allergen presentation to T cells	180:211	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	1	57	theme	migration	287:295	arg1	regulation					214:223	regulation	214:223	regulation of IgE responses	214:240	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	10	58	theme	IgE	1671:1673	arg1	binding					1675:1681	IgE binding	1671:1681	IgE binding	1671:1681	We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab.
27343203	4	59	theme	extracellular	539:551	arg1	portion					553:559	the full extracellular portion	530:559	the full extracellular portion of CD23	530:567	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	7	60	theme	unknown	1203:1209	arg1	site					1223:1226	A hitherto unknown IgE-binding site	1192:1226	A hitherto unknown IgE-binding site	1192:1226	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	8	61	theme	IgE	1513:1515	arg1	binding					1517:1523	IgE binding	1513:1523	IgE binding to CD23	1513:1531	Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23.
27343203	2	62	from	level	462:466	arg1	interaction					338:348	the interaction	334:348	the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level	334:466	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	6	63	theme	CD23	1079:1082	arg1	surface					1084:1090	the CD23 surface	1075:1090	the CD23 surface	1075:1090	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	5	64	theme	gel	917:919	arg1	filtration					921:930	gel filtration	917:930	gel filtration	917:930	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	6	65	theme	Bet	1009:1011	arg1	mAb					977:979	a human IgE mAb	965:979	a human IgE mAb	965:979	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	65	theme	Bet	1009:1011	arg1	v					1013:1013	the corresponding allergen Bet v 1	982:1015	the corresponding allergen Bet v 1	982:1015	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	66	theme	allergen	1000:1007	arg1	mAb					977:979	a human IgE mAb	965:979	a human IgE mAb	965:979	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	66	theme	allergen	1000:1007	arg1	v					1013:1013	the corresponding allergen Bet v 1	982:1015	the corresponding allergen Bet v 1	982:1015	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	5	67	theme	folded	881:886	arg1	proteins					888:895	monomeric and structurally folded proteins	854:895	monomeric and structurally folded proteins	854:895	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	5	67	theme	folded	881:886	arg1	variants					828:835	The 4 CD23 variants	817:835	The 4 CD23 variants	817:835	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	7	68	theme	monomeric	1295:1303	arg1	superior					1325:1332	superior	1325:1332	superior	1325:1332	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	7	68	theme	monomeric	1295:1303	arg1	version					1305:1311	the non-N-glycosylated monomeric version	1272:1311	the non-N-glycosylated monomeric version of CD23	1272:1319	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	5	69	theme	CD23	823:826	arg1	variants					828:835	The 4 CD23 variants	817:835	The 4 CD23 variants	817:835	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	5	69	theme	CD23	823:826	arg1	proteins					888:895	monomeric and structurally folded proteins	854:895	monomeric and structurally folded proteins	854:895	The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism.
27343203	7	70	gly	glycosylated	1363:1374	arg1	CD23					1376:1379	glycosylated CD23	1363:1379	glycosylated CD23	1363:1379	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	2	71	theme	molecular	452:460	arg1	level					462:466	a molecular level	450:466	a molecular level	450:466	OBJECTIVE: We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level.
27343203	1	72	theme	allergen	180:187	arg1	presentation					189:200	allergen presentation	180:200	allergen presentation to T cells	180:211	BACKGROUND: The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration.
27343203	4	73	theme	N-linked	716:723	arg1	site					739:742	the N-linked glycosylation site	712:742	the N-linked glycosylation site	712:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	4	74	link	N-linked	716:723	arg1	site					739:742	the N-linked glycosylation site	712:742	the N-linked glycosylation site	712:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	6	75	theme	corresponding	986:998	arg1	mAb					977:979	a human IgE mAb	965:979	a human IgE mAb	965:979	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	75	theme	corresponding	986:998	arg1	v					1013:1013	the corresponding allergen Bet v 1	982:1015	the corresponding allergen Bet v 1	982:1015	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	76	theme	human	967:971	arg1	mAb					977:979	a human IgE mAb	965:979	a human IgE mAb	965:979	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	6	76	theme	human	967:971	arg1	v					1013:1013	the corresponding allergen Bet v 1	982:1015	the corresponding allergen Bet v 1	982:1015	By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed.
27343203	4	77	theme	full	534:537	arg1	portion					553:559	the full extracellular portion	530:559	the full extracellular portion of CD23	530:567	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	0	78	theme	region	50:55	arg1	involvement					20:30	Critical and direct involvement	0:30	Critical and direct involvement of the CD23 stalk region in IgE binding.	0:71	Critical and direct involvement of the CD23 stalk region in IgE binding.
27343203	0	79	from	involvement	20:30	arg1	binding					64:70	IgE binding	60:70	IgE binding	60:70	Critical and direct involvement of the CD23 stalk region in IgE binding.
27343203	7	80	from	superior	1325:1332	arg1	binding					1341:1347	IgE binding	1337:1347	IgE binding	1337:1347	RESULTS: A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23.
27343203	4	81	gly	glycosylation	725:737	arg2	site					739:742	the N-linked glycosylation site	712:742	the N-linked glycosylation site	712:742	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
27343203	4	82	theme	CD23	564:567	arg1	portion					553:559	the full extracellular portion	530:559	the full extracellular portion of CD23	530:567	One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated.
28878070	7	0	theme	recombinant	1382:1392	arg1	viruses					1394:1400	the recombinant viruses	1378:1400	the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78	1378:1468	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	4	1	theme	reporter	769:776	arg1	gene					778:781	the reporter gene	765:781	the reporter gene	765:781	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	2	2	link	disulfide-linked	306:321	arg1	oligomerization					323:337	disulfide-linked oligomerization	306:337	disulfide-linked oligomerization	306:337	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	6	3	theme	recombinant	1162:1172	arg1	virus					1186:1190	the recombinant influenza C virus	1158:1190	the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78	1158:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	2	4	theme	oligomerization	323:337	arg1	effects					271:277	the effects	267:277	the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication	267:385	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	9	5	theme	nuclear	2001:2007	arg1	NEP					2025:2027	NEP	2025:2027	NEP	2025:2027	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	5	theme	nuclear	2001:2007	arg1	proteins					1971:1978	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	5	theme	nuclear	2001:2007	arg1	protein					2016:2022	the nuclear export protein	1997:2022	the nuclear export protein (NEP)	1997:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	10	6	theme	virus	2219:2223	arg1	phosphorylation					2184:2198	phosphorylation	2184:2198	phosphorylation	2184:2198	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	8	7	theme	CM2	1612:1614	arg1	phosphorylation					1593:1607	phosphorylation	1593:1607	phosphorylation of CM2	1593:1614	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	1	8	theme	influenza	227:235	arg1	virus					239:243	influenza C virus	227:243	influenza C virus replication	227:255	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	7	9	theme	virus	1362:1366	arg1	identical					1524:1532	identical	1524:1532	identical	1524:1532	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	7	9	theme	virus	1362:1366	arg1	growth					1368:1373	the virus growth	1358:1373	the virus growth	1358:1373	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	8	10	dep	site.IMPORTANCE	1741:1755	arg1	well-known					1763:1772	well-known	1763:1772	well-known	1763:1772	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	10	11	theme	virus	2305:2309	arg1	replication					2311:2321	virus replication	2305:2321	virus replication in vitro or in vivo	2305:2341	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	6	12	theme	virus	1138:1142	arg1	production					1144:1153	The virus production	1134:1153	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78	1134:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	6	12	theme	virus	1138:1142	arg1	lower					1285:1289	lower	1285:1289	lower	1285:1289	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	7	13	with	CM2	1413:1415	arg1	change					1448:1453	a serine-to-aspartic acid change	1422:1453	a serine-to-aspartic acid change at position 78	1422:1468	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	3	14	from	effects	617:623	arg1	replication					677:687	influenza C virus replication	659:687	influenza C virus replication	659:687	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	3	15	theme	phosphorylation	640:654	arg1	loss					632:635	the loss	628:635	the loss of phosphorylation	628:654	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	8	16	theme	viral	1793:1797	arg1	proteins					1799:1806	many host and viral proteins	1779:1806	proteins	1799:1806	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	3	17	theme	loss	632:635	arg1	effects					617:623	the effects	613:623	the effects of the loss of phosphorylation on influenza C virus replication	613:687	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	3	18	theme	phosphorylation	512:526	arg1	s					533:533	s	533:533	s	533:533	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	3	18	theme	phosphorylation	512:526	arg1	site					528:531	a phosphorylation site	510:531	a phosphorylation site(s) at residue 78	510:548	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	8	19	theme	virus	1642:1646	arg1	replication					1648:1658	efficient virus replication	1632:1658	efficient virus replication	1632:1658	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	3	20	theme	virus	671:675	arg1	replication					677:687	influenza C virus replication	659:687	influenza C virus replication	659:687	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	1	21	from	processes	214:222	arg1	replication					245:255	influenza C virus replication	227:255	influenza C virus replication	227:255	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	4	22	theme	C	801:801	arg1	VLPs					825:828	VLPs	825:828	VLPs	825:828	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	4	22	theme	C	801:801	arg1	particles					814:822	influenza C virus-like particles	791:822	influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s)	791:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	3	23	theme	influenza	659:667	arg1	virus					671:675	influenza C virus	659:675	influenza C virus replication	659:687	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	6	24	theme	C	1184:1184	arg1	virus					1186:1190	the recombinant influenza C virus	1158:1190	the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78	1158:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	9	25	dep	proteins	1971:1978	arg1	protein					2016:2022	the nuclear export protein	1997:2022	the nuclear export protein (NEP)	1997:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	25	dep	proteins	1971:1978	arg1	NS1					1988:1990	NS1	1988:1990	NS1	1988:1990	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	25	dep	proteins	1971:1978	arg1	proteins					1971:1978	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	25	dep	proteins	1971:1978	arg1	NEP					2025:2027	NEP	2025:2027	NEP	2025:2027	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	25	dep	proteins	1971:1978	arg1	NP					1980:1981	NP	1980:1981	NP	1980:1981	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	25	dep	proteins	1971:1978	arg1	M1					1984:1985	M1	1984:1985	M1	1984:1985	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	10	26	theme	M2	2225:2226	arg1	protein					2240:2246	M2 ion channel protein	2225:2246	the influenza A virus M2 ion channel protein	2203:2246	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	27	contain	has	2288:2290	arg1	phosphorylation					2184:2198	phosphorylation	2184:2198	phosphorylation	2184:2198	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	27	contain	has	2288:2290	arg2	effect					2295:2300	no effect	2292:2300	no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication	2292:2603	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	28	theme	influenza	2379:2387	arg1	CM2					2397:2399	the influenza C virus CM2	2375:2399	the influenza C virus CM2 ion channel protein	2375:2419	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	0	29	theme	C	54:54	arg1	Virus					56:60	Influenza C Virus	44:60	Influenza C Virus Replication	44:72	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.
28878070	0	30	theme	Phosphorylation	10:24	arg1	Effect					0:5	Effect	0:5	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.	0:73	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.
28878070	1	31	theme	C	127:127	arg1	virus					129:133	the influenza C virus	113:133	the influenza C virus	113:133	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	2	32	theme	virus	451:455	arg1	replication					457:467	virus replication	451:467	virus replication	451:467	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	5	33	contain	containing	1030:1039	arg2	mutants					1049:1055	the CM2 mutants	1041:1055	the CM2 mutants	1041:1055	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	5	33	contain	containing	1030:1039	arg1	VLPs					1025:1028	VLPs	1025:1028	VLPs containing the CM2 mutants	1025:1055	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	8	34	theme	charge	1705:1710	arg1	addition					1682:1689	the addition	1678:1689	the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins	1678:1913	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	6	35	contain	possessing	1192:1201	arg1	virus					1186:1190	the recombinant influenza C virus	1158:1190	the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78	1158:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	6	35	contain	possessing	1192:1201	arg2	mutants					1207:1213	CM2 mutants	1203:1213	CM2 mutants containing a serine-to-alanine change at residue 78	1203:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	5	36	from	expression	984:993	arg1	cells					1005:1009	HMV-II cells	998:1009	HMV-II cells infected with VLPs containing the CM2 mutants	998:1055	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	4	37	theme	293T	845:848	arg1	cells					850:854	293T cells	845:854	293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s)	845:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	0	38	from	Effect	0:5	arg1	Replication					62:72	Influenza C Virus Replication	44:72	Influenza C Virus Replication	44:72	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.
28878070	10	39	theme	ion	2401:2403	arg1	protein					2413:2419	the influenza C virus CM2 ion channel protein	2375:2419	the influenza C virus CM2 ion channel protein	2375:2419	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	11	40	theme	virus	2685:2689	arg1	protein					2707:2713	the influenza C virus CM2 ion channel protein	2669:2713	the influenza C virus CM2 ion channel protein	2669:2713	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	5	41	theme	gene	979:982	arg1	expression					984:993	Reporter gene expression	970:993	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants	970:1055	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	10	42	theme	channel	2232:2238	arg1	protein					2240:2246	M2 ion channel protein	2225:2246	the influenza A virus M2 ion channel protein	2203:2246	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	43	theme	virus	2587:2591	arg1	replication					2593:2603	virus replication	2587:2603	virus replication	2587:2603	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	9	44	theme	A	1929:1929	arg1	viruses					1937:1943	influenza A and B viruses	1919:1943	influenza A and B viruses	1919:1943	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	10	45	theme	virus	2391:2395	arg1	CM2					2397:2399	the influenza C virus CM2	2375:2399	the influenza C virus CM2 ion channel protein	2375:2419	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	2	46	theme	virus	369:373	arg1	replication					375:385	virus replication	369:385	virus replication	369:385	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	0	47	theme	Protein	33:39	arg1	Phosphorylation					10:24	Phosphorylation	10:24	Phosphorylation of CM2 Protein	10:39	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.
28878070	8	48	theme	phosphorylation	1725:1739	arg1	site.IMPORTANCE					1741:1755	the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins	1715:1913	the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins	1715:1913	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	4	49	theme	CM2	921:923	arg1	mutants					925:931	the CM2 mutants	917:931	the CM2 mutants lacking the phosphorylation site(s)	917:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	9	50	theme	B	1935:1935	arg1	viruses					1937:1943	influenza A and B viruses	1919:1943	influenza A and B viruses	1919:1943	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	11	51	theme	CM2	2691:2693	arg1	protein					2707:2713	the influenza C virus CM2 ion channel protein	2669:2713	the influenza C virus CM2 ion channel protein	2669:2713	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	10	52	theme	A	2217:2217	arg1	virus					2219:2223	the influenza A virus M2 ion channel protein	2203:2246	the influenza A virus M2 ion channel protein	2203:2246	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	2	53	theme	CM2	362:364	arg1	glycosylation					291:303	N-linked glycosylation	282:303	N-linked glycosylation	282:303	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	2	53	theme	CM2	362:364	arg1	oligomerization					323:337	disulfide-linked oligomerization	306:337	disulfide-linked oligomerization	306:337	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	2	53	theme	CM2	362:364	arg1	palmitoylation					344:357	palmitoylation	344:357	palmitoylation of CM2	344:364	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	11	54	dep	virus	2747:2751	arg1	protein					2756:2762	M2 protein	2753:2762	the influenza A virus M2 protein	2731:2762	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	1	55	theme	C	237:237	arg1	virus					239:243	influenza C virus	227:243	influenza C virus replication	227:255	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	11	56	theme	C	2683:2683	arg1	virus					2685:2689	influenza C virus	2673:2689	the influenza C virus CM2 ion channel protein	2669:2713	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	9	57	theme	virus	2135:2139	arg1	replication					2141:2151	virus replication	2135:2151	virus replication	2135:2151	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	6	58	theme	influenza	1326:1334	arg1	virus					1338:1342	wild-type recombinant influenza C virus	1304:1342	wild-type recombinant influenza C virus	1304:1342	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	7	59	from	position	1458:1465	arg1	change					1448:1453	a serine-to-aspartic acid change	1422:1453	a serine-to-aspartic acid change at position 78	1422:1468	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	7	60	theme	acid	1443:1446	arg1	change					1448:1453	a serine-to-aspartic acid change	1422:1453	a serine-to-aspartic acid change at position 78	1422:1468	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	1	61	theme	second	86:91	arg1	protein					102:108	the second membrane protein	82:108	the second membrane protein of the influenza C virus	82:133	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	1	61	theme	second	86:91	arg1	CM2					75:77	CM2	75:77	CM2	75:77	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	7	62	theme	wild-type	1549:1557	arg1	virus					1559:1563	the wild-type virus	1545:1563	the wild-type virus	1545:1563	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	2	63	theme	CM2	444:446	arg1	phosphorylation					425:439	the phosphorylation	421:439	the phosphorylation of CM2	421:446	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	3	64	from	residue	539:545	arg1	s					533:533	s	533:533	s	533:533	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	3	64	from	residue	539:545	arg1	site					528:531	a phosphorylation site	510:531	a phosphorylation site(s) at residue 78	510:548	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	6	65	theme	wild-type	1304:1312	arg1	virus					1338:1342	wild-type recombinant influenza C virus	1304:1342	wild-type recombinant influenza C virus	1304:1342	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	0	66	theme	CM2	29:31	arg1	Protein					33:39	CM2 Protein	29:39	CM2 Protein	29:39	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.
28878070	2	67	theme	phosphorylation	425:439	arg1	effect					411:416	the effect	407:416	the effect of the phosphorylation of CM2 on virus replication	407:467	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	9	68	theme	proteins	1971:1978	arg1	phosphorylation					1946:1960	phosphorylation	1946:1960	phosphorylation	1946:1960	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	2	69	theme	disulfide-linked	306:321	arg1	oligomerization					323:337	disulfide-linked oligomerization	306:337	disulfide-linked oligomerization	306:337	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	11	70	theme	protein	2707:2713	arg1	phosphorylation					2650:2664	phosphorylation	2650:2664	phosphorylation of the influenza C virus CM2 ion channel protein	2650:2713	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	5	71	theme	CM2	1045:1047	arg1	mutants					1049:1055	the CM2 mutants	1041:1055	the CM2 mutants	1041:1055	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	11	72	theme	influenza	2735:2743	arg1	virus					2747:2751	the influenza A virus M2 protein	2731:2762	the influenza A virus M2 protein	2731:2762	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	9	73	theme	viral	1965:1969	arg1	M1					1984:1985	M1	1984:1985	M1	1984:1985	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	73	theme	viral	1965:1969	arg1	NS1					1988:1990	NS1	1988:1990	NS1	1988:1990	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	73	theme	viral	1965:1969	arg1	proteins					1971:1978	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	73	theme	viral	1965:1969	arg1	protein					2016:2022	the nuclear export protein	1997:2022	the nuclear export protein (NEP)	1997:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	73	theme	viral	1965:1969	arg1	NP					1980:1981	NP	1980:1981	NP	1980:1981	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	10	74	mod	modified	2424:2431	arg3	phosphorylation					2490:2504	phosphorylation	2490:2504	phosphorylation	2490:2504	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	74	mod	modified	2424:2431	arg1	protein					2413:2419	the influenza C virus CM2 ion channel protein	2375:2419	the influenza C virus CM2 ion channel protein	2375:2419	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	74	mod	modified	2424:2431	arg3	N-glycosylation					2436:2450	N-glycosylation	2436:2450	N-glycosylation	2436:2450	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	74	mod	modified	2424:2431	arg3	oligomerization					2453:2467	oligomerization	2453:2467	oligomerization	2453:2467	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	74	mod	modified	2424:2431	arg3	palmitoylation					2470:2483	palmitoylation	2470:2483	palmitoylation	2470:2483	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	2	75	theme	glycosylation	291:303	arg1	effects					271:277	the effects	267:277	the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication	267:385	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	10	76	dep	virus	2219:2223	arg1	protein					2240:2246	M2 ion channel protein	2225:2246	the influenza A virus M2 ion channel protein	2203:2246	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	7	77	theme	viruses	1394:1400	arg1	identical					1524:1532	identical	1524:1532	identical	1524:1532	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	7	77	theme	viruses	1394:1400	arg1	growth					1368:1373	the virus growth	1358:1373	the virus growth	1358:1373	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	3	78	theme	alanine	589:595	arg1	s					605:605	s	605:605	s	605:605	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	3	78	theme	alanine	589:595	arg1	residue					597:603	an alanine residue	586:603	an alanine residue(s)	586:606	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	11	79	theme	first	2618:2622	arg1	report					2624:2629	the first report	2614:2629	the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication	2614:2797	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	11	79	theme	first	2618:2622	arg1	This					2606:2609	This	2606:2609	This	2606:2609	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	2	80	theme	palmitoylation	344:357	arg1	effects					271:277	the effects	267:277	the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication	267:385	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	5	81	theme	wild-type	1118:1126	arg1	VLPs					1128:1131	wild-type VLPs	1118:1131	wild-type VLPs	1118:1131	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	4	82	theme	phosphorylation	945:959	arg1	site					961:964	the phosphorylation site	941:964	the phosphorylation site(s)	941:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	4	82	theme	phosphorylation	945:959	arg1	s					966:966	s	966:966	s	966:966	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	4	83	located	observed	736:743	arg1	packaging					752:760	the packaging	748:760	the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s)	748:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	4	83	located	observed	736:743	arg2	differences					719:729	No significant differences	704:729	No significant differences	704:729	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	2	84	link	N-linked	282:289	arg1	glycosylation					291:303	N-linked glycosylation	282:303	N-linked glycosylation	282:303	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	6	85	theme	influenza	1174:1182	arg1	virus					1186:1190	the recombinant influenza C virus	1158:1190	the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78	1158:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	1	86	theme	packaging	204:212	arg1	processes					214:222	the uncoating and genome packaging processes	179:222	the uncoating and genome packaging processes in influenza C virus replication	179:255	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	8	87	theme	many	1779:1782	arg1	host					1784:1787	many host and viral proteins	1779:1806	host	1784:1787	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	4	88	theme	gene	778:781	arg1	packaging					752:760	the packaging	748:760	the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s)	748:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	9	89	theme	export	2009:2014	arg1	NEP					2025:2027	NEP	2025:2027	NEP	2025:2027	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	89	theme	export	2009:2014	arg1	proteins					1971:1978	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	viral proteins NP, M1, NS1, and the nuclear export protein (NEP)	1965:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	9	89	theme	export	2009:2014	arg1	protein					2016:2022	the nuclear export protein	1997:2022	the nuclear export protein (NEP)	1997:2028	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	7	90	contain	possessing	1402:1411	arg1	viruses					1394:1400	the recombinant viruses	1378:1400	the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78	1378:1468	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	7	90	contain	possessing	1402:1411	arg2	CM2					1413:1415	CM2	1413:1415	CM2 with a serine-to-aspartic acid change at position 78	1413:1468	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	5	91	with	comparison	1074:1083	arg1	that					1090:1093	that	1090:1093	that	1090:1093	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	6	92	theme	serine-to-alanine	1228:1244	arg1	change					1246:1251	a serine-to-alanine change	1226:1251	a serine-to-alanine change	1226:1251	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	11	93	theme	virus	2781:2785	arg1	replication					2787:2797	virus replication	2781:2797	virus replication	2781:2797	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	8	94	theme	efficient	1632:1640	arg1	replication					1648:1658	efficient virus replication	1632:1658	efficient virus replication	1632:1658	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	10	95	from	effect	2295:2300	arg1	replication					2311:2321	virus replication	2305:2321	virus replication in vitro or in vivo	2305:2341	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	96	from	effects	2528:2534	arg1	replication					2593:2603	virus replication	2587:2603	virus replication	2587:2603	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	6	97	theme	CM2	1203:1205	arg1	mutants					1207:1213	CM2 mutants	1203:1213	CM2 mutants containing a serine-to-alanine change at residue 78	1203:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	5	98	theme	Reporter	970:977	arg1	expression					984:993	Reporter gene expression	970:993	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants	970:1055	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	1	99	theme	membrane	93:100	arg1	protein					102:108	the second membrane protein	82:108	the second membrane protein of the influenza C virus	82:133	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	1	99	theme	membrane	93:100	arg1	CM2					75:77	CM2	75:77	CM2	75:77	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	2	100	from	effect	411:416	arg1	replication					457:467	virus replication	451:467	virus replication	451:467	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	4	101	theme	influenza	791:799	arg1	VLPs					825:828	VLPs	825:828	VLPs	825:828	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	4	101	theme	influenza	791:799	arg1	particles					814:822	influenza C virus-like particles	791:822	influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s)	791:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	3	102	theme	C	669:669	arg1	virus					671:675	influenza C virus	659:675	influenza C virus replication	659:687	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	6	103	theme	virus	1186:1190	arg1	production					1144:1153	The virus production	1134:1153	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78	1134:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	6	103	theme	virus	1186:1190	arg1	lower					1285:1289	lower	1285:1289	lower	1285:1289	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	10	104	dep	effect	2295:2300	arg1	demonstrated					2357:2368	demonstrated	2357:2368	demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication	2357:2603	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	6	105	contain	containing	1215:1224	arg2	change					1246:1251	a serine-to-alanine change	1226:1251	a serine-to-alanine change	1226:1251	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	6	105	contain	containing	1215:1224	arg1	mutants					1207:1213	CM2 mutants	1203:1213	CM2 mutants containing a serine-to-alanine change at residue 78	1203:1265	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	7	106	theme	constitutive	1480:1491	arg1	phosphorylation					1493:1507	constitutive phosphorylation	1480:1507	constitutive phosphorylation	1480:1507	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	4	107	theme	virus-like	803:812	arg1	VLPs					825:828	VLPs	825:828	VLPs	825:828	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	4	107	theme	virus-like	803:812	arg1	particles					814:822	influenza C virus-like particles	791:822	influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s)	791:967	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	0	108	theme	Virus	56:60	arg1	Replication					62:72	Influenza C Virus Replication	44:72	Influenza C Virus Replication	44:72	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.
28878070	1	109	theme	influenza	117:125	arg1	virus					129:133	the influenza C virus	113:133	the influenza C virus	113:133	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	4	110	theme	wild-type	867:875	arg1	CM2					877:879	wild-type CM2	867:879	wild-type CM2	867:879	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	11	111	theme	M2	2753:2754	arg1	protein					2756:2762	M2 protein	2753:2762	the influenza A virus M2 protein	2731:2762	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	1	112	theme	virus	129:133	arg1	protein					102:108	the second membrane protein	82:108	the second membrane protein of the influenza C virus	82:133	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	1	112	theme	virus	129:133	arg1	CM2					75:77	CM2	75:77	CM2	75:77	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	10	113	theme	influenza	2207:2215	arg1	virus					2219:2223	the influenza A virus M2 ion channel protein	2203:2246	the influenza A virus M2 ion channel protein	2203:2246	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	11	114	theme	A	2745:2745	arg1	virus					2747:2751	the influenza A virus M2 protein	2731:2762	the influenza A virus M2 protein	2731:2762	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	8	115	theme	negative	1696:1703	arg1	charge					1705:1710	a negative charge	1694:1710	a negative charge	1694:1710	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	2	116	from	effects	271:277	arg1	replication					375:385	virus replication	369:385	virus replication	369:385	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	11	117	theme	influenza	2673:2681	arg1	virus					2685:2689	influenza C virus	2673:2689	the influenza C virus CM2 ion channel protein	2669:2713	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	9	118	theme	influenza	1919:1927	arg1	A					1929:1929	influenza A	1919:1929	influenza A	1919:1929	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	10	119	theme	CM2	2397:2399	arg1	protein					2413:2419	the influenza C virus CM2 ion channel protein	2375:2419	the influenza C virus CM2 ion channel protein	2375:2419	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	8	120	theme	proteins	1906:1913	arg1	functions					1887:1895	the functions	1883:1895	the functions of these proteins	1883:1913	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	8	121	mod	modified	1832:1839	arg3	phosphorylation					1844:1858	phosphorylation	1844:1858	phosphorylation	1844:1858	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	8	121	mod	modified	1832:1839	arg1	host					1784:1787	many host and viral proteins	1779:1806	host	1784:1787	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	8	121	mod	modified	1832:1839	arg1	proteins					1799:1806	many host and viral proteins	1779:1806	proteins	1799:1806	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	10	122	theme	ion	2228:2230	arg1	protein					2240:2246	M2 ion channel protein	2225:2246	the influenza A virus M2 ion channel protein	2203:2246	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	10	123	theme	C	2389:2389	arg1	CM2					2397:2399	the influenza C virus CM2	2375:2399	the influenza C virus CM2 ion channel protein	2375:2419	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	5	124	theme	HMV-II	998:1003	arg1	cells					1005:1009	HMV-II cells	998:1009	HMV-II cells infected with VLPs containing the CM2 mutants	998:1055	Reporter gene expression in HMV-II cells infected with VLPs containing the CM2 mutants was inhibited in comparison with that in cells infected with wild-type VLPs.
28878070	8	125	theme	Ser78	1719:1723	arg1	site.IMPORTANCE					1741:1755	the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins	1715:1913	the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins	1715:1913	These results suggest that phosphorylation of CM2 plays a role in efficient virus replication, probably through the addition of a negative charge to the Ser78 phosphorylation site.IMPORTANCE It is well-known that many host and viral proteins are posttranslationally modified by phosphorylation, which plays a role in the functions of these proteins.
28878070	11	126	theme	ion	2695:2697	arg1	protein					2707:2713	the influenza C virus CM2 ion channel protein	2669:2713	the influenza C virus CM2 ion channel protein	2669:2713	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	6	127	theme	C	1336:1336	arg1	virus					1338:1342	wild-type recombinant influenza C virus	1304:1342	wild-type recombinant influenza C virus	1304:1342	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	1	128	theme	virus	239:243	arg1	replication					245:255	influenza C virus replication	227:255	influenza C virus replication	227:255	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	10	129	theme	channel	2405:2411	arg1	protein					2413:2419	the influenza C virus CM2 ion channel protein	2375:2419	the influenza C virus CM2 ion channel protein	2375:2419	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	6	130	theme	recombinant	1314:1324	arg1	virus					1338:1342	wild-type recombinant influenza C virus	1304:1342	wild-type recombinant influenza C virus	1304:1342	The virus production of the recombinant influenza C virus possessing CM2 mutants containing a serine-to-alanine change at residue 78 was significantly lower than that of wild-type recombinant influenza C virus.
28878070	11	131	theme	channel	2699:2705	arg1	protein					2707:2713	the influenza C virus CM2 ion channel protein	2669:2713	the influenza C virus CM2 ion channel protein	2669:2713	This is the first report demonstrating that phosphorylation of the influenza C virus CM2 ion channel protein, unlike that of the influenza A virus M2 protein, plays a role in virus replication.
28878070	9	132	theme	proteins	2107:2114	arg1	functions					2088:2096	the functions	2084:2096	the functions of these proteins	2084:2114	In influenza A and B viruses, phosphorylation of viral proteins NP, M1, NS1, and the nuclear export protein (NEP), which are not integrated into the membranes, affects the functions of these proteins, thereby affecting virus replication.
28878070	3	133	theme	CM2	564:566	arg1	CM2					564:566	CM2	564:566	CM2	564:566	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	3	133	theme	CM2	564:566	arg1	103					557:559	103	557:559	103	557:559	In this study, a phosphorylation site(s) at residue 78 and/or 103 of CM2 was replaced with an alanine residue(s), and the effects of the loss of phosphorylation on influenza C virus replication were analyzed.
28878070	4	134	theme	significant	707:717	arg1	differences					719:729	No significant differences	704:729	No significant differences	704:729	No significant differences were observed in the packaging of the reporter gene between influenza C virus-like particles (VLPs) produced from 293T cells expressing wild-type CM2 and those from the cells expressing the CM2 mutants lacking the phosphorylation site(s).
28878070	0	135	theme	Influenza	44:52	arg1	Virus					56:60	Influenza C Virus	44:60	Influenza C Virus Replication	44:72	Effect of Phosphorylation of CM2 Protein on Influenza C Virus Replication.
28878070	7	136	theme	serine-to-aspartic	1424:1441	arg1	change					1448:1453	a serine-to-aspartic acid change	1422:1453	a serine-to-aspartic acid change at position 78	1422:1468	Furthermore, the virus growth of the recombinant viruses possessing CM2 with a serine-to-aspartic acid change at position 78, to mimic constitutive phosphorylation, was virtually identical to that of the wild-type virus.
28878070	2	137	gly	glycosylation	291:303	arg1	virus					369:373	virus replication	369:385	virus replication	369:385	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	2	137	gly	glycosylation	291:303	arg1	CM2					362:364	CM2	362:364	CM2	362:364	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	2	138	theme	N-linked	282:289	arg1	glycosylation					291:303	N-linked glycosylation	282:303	N-linked glycosylation	282:303	Although the effects of N-linked glycosylation, disulfide-linked oligomerization, and palmitoylation of CM2 on virus replication have been analyzed, the effect of the phosphorylation of CM2 on virus replication remains to be determined.
28878070	1	139	theme	uncoating	183:191	arg1	processes					214:222	the uncoating and genome packaging processes	179:222	the uncoating and genome packaging processes in influenza C virus replication	179:255	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
28878070	10	140	theme	modifications	2545:2557	arg1	effects					2528:2534	the effects	2524:2534	the effects of these modifications, except phosphorylation, on virus replication	2524:2603	However, it was reported that phosphorylation of the influenza A virus M2 ion channel protein, which is integrated into the membrane, has no effect on virus replication in vitro or in vivo We previously demonstrated that the influenza C virus CM2 ion channel protein is modified by N-glycosylation, oligomerization, palmitoylation, and phosphorylation and have analyzed the effects of these modifications, except phosphorylation, on virus replication.
28878070	1	141	theme	genome	197:202	arg1	packaging					204:212	genome packaging	197:212	genome packaging	197:212	CM2 is the second membrane protein of the influenza C virus and has been demonstrated to play a role in the uncoating and genome packaging processes in influenza C virus replication.
29030255	6	0	theme	CA	737:738	arg1	zebrafish					759:767	zebrafish	759:767	zebrafish	759:767	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	0	theme	CA	737:738	arg1	arowana					776:782	Asian arowana	770:782	Asian arowana	770:782	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	0	theme	CA	737:738	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	0	theme	CA	737:738	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	0	theme	CA	737:738	arg1	salmon					785:790	salmon	785:790	salmon	785:790	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	5	1	dep	CA	669:670	arg1	VI					672:673	VI	672:673	VI	672:673	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	4	2	theme	acid	499:502	arg1	sequence					504:511	a deduced amino acid sequence	483:511	a deduced amino acid sequence of 540 amino acids from the open reading frame	483:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	6	3	theme	other	726:730	arg1	zebrafish					759:767	zebrafish	759:767	zebrafish	759:767	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	3	theme	other	726:730	arg1	arowana					776:782	Asian arowana	770:782	Asian arowana	770:782	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	3	theme	other	726:730	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	3	theme	other	726:730	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	3	theme	other	726:730	arg1	salmon					785:790	salmon	785:790	salmon	785:790	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	12	4	theme	Homology	1505:1512	arg1	modeling					1514:1521	Homology modeling	1505:1521	Homology modeling of puffer CA VI	1505:1537	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	7	5	theme	pufferfish	903:912	arg1	CA					914:915	pufferfish CA VI	903:918	pufferfish CA VI	903:918	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	13	6	theme	transcription-polymerase	1672:1695	arg1	reaction					1703:1710	Reverse transcription-polymerase chain reaction	1664:1710	Reverse transcription-polymerase chain reaction (PCR)	1664:1716	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	13	6	theme	transcription-polymerase	1672:1695	arg1	PCR					1713:1715	PCR	1713:1715	PCR	1713:1715	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	5	7	theme	gar	665:667	arg1	CA					669:670	gar CA VI	665:673	gar CA VI	665:673	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	9	8	from	CA	1251:1252	arg1	present					1229:1235	present	1229:1235	present	1229:1235	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	10	9	theme	extracellular	1331:1343	arg1	CA					1319:1320	pufferfish CA VI	1308:1323	pufferfish CA VI	1308:1323	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	10	9	theme	extracellular	1331:1343	arg1	protein					1355:1361	an extracellular secretory protein	1328:1361	an extracellular secretory protein	1328:1361	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	13	10	theme	reaction	1703:1710	arg1	results					1762:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results	1664:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results	1664:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	4	11	from	frame	554:558	arg1	sequence					460:467	a complete coding sequence	442:467	a complete coding sequence of 1623bp	442:477	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	4	11	from	frame	554:558	arg1	sequence					504:511	a deduced amino acid sequence	483:511	a deduced amino acid sequence of 540 amino acids from the open reading frame	483:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	4	11	from	frame	554:558	arg1	acids					526:530	540 amino acids	516:530	540 amino acids from the open reading frame	516:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	8	12	theme	acids	1025:1029	arg1	peptide					1005:1011	An NH2-terminal signal peptide	982:1011	An NH2-terminal signal peptide of 18 amino acids in length	982:1039	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	9	13	theme	disulfide	1209:1217	arg1	bond					1219:1222	one disulfide bond	1205:1222	one disulfide bond	1205:1222	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	6	14	theme	Asian	770:774	arg1	arowana					776:782	Asian arowana	770:782	Asian arowana	770:782	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	14	theme	Asian	770:774	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	0	15	from	pufferfish	77:86	arg1	characterization					22:37	characterization	22:37	characterization	22:37	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	0	15	from	pufferfish	77:86	arg1	cloning					10:16	Molecular cloning	0:16	Molecular cloning	0:16	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	10	16	dep	CA	1319:1320	arg1	VI					1322:1323	VI	1322:1323	VI	1322:1323	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	4	17	from	sequence	504:511	arg1	frame					554:558	the open reading frame	537:558	the open reading frame	537:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	2	18	theme	present	201:207	arg1	study					209:213	Our present study	197:213	Our present study	197:213	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	8	19	theme	NH2-terminal	985:996	arg1	peptide					1005:1011	An NH2-terminal signal peptide	982:1011	An NH2-terminal signal peptide of 18 amino acids in length	982:1039	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	9	20	dep	residues	1151:1158	arg1	Cys-209					1172:1178	Cys-209	1172:1178	Cys-209	1172:1178	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	20	dep	residues	1151:1158	arg1	Cys-28					1161:1166	Cys-28	1161:1166	Cys-28	1161:1166	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	20	dep	residues	1151:1158	arg1	residues					1151:1158	two cysteine residues	1138:1158	two cysteine residues (Cys-28 and Cys-209)	1138:1179	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	8	21	from	peptide	1005:1011	arg1	length					1034:1039	length	1034:1039	length	1034:1039	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	5	22	with	identity	631:638	arg1	tilapia					652:658	tilapia	652:658	tilapia	652:658	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	5	22	with	identity	631:638	arg1	human					645:649	human	645:649	human	645:649	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	5	22	with	identity	631:638	arg1	CA					669:670	gar CA VI	665:673	gar CA VI	665:673	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	2	23	from	pufferfish	252:261	arg1	occurrence					229:238	the occurrence	225:238	the occurrence of CA VI in pufferfish (Takifugu rubripes)	225:281	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	8	24	theme	CA	1073:1074	arg1	sequence					1079:1086	the pufferfish CA VI sequence	1058:1086	the pufferfish CA VI sequence	1058:1086	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	13	25	theme	Reverse	1664:1670	arg1	reaction					1703:1710	Reverse transcription-polymerase chain reaction	1664:1710	Reverse transcription-polymerase chain reaction (PCR)	1664:1716	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	13	25	theme	Reverse	1664:1670	arg1	PCR					1713:1715	PCR	1713:1715	PCR	1713:1715	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	5	26	theme	%	629:629	arg1	identity					631:638	67% identity	627:638	67% identity with human, tilapia, and gar CA VI	627:673	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	7	27	dep	%	930:930	arg1	%					926:926	%	926:926	%	926:926	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	10	28	dep	In	1258:1259	arg1	silico					1261:1266	silico	1261:1266	silico	1261:1266	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	12	29	theme	high	1647:1650	arg1	similarity					1652:1661	high similarity	1647:1661	high similarity	1647:1661	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	6	30	theme	large	797:801	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	30	theme	large	797:801	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	3	31	theme	sequence	307:314	arg1	information					316:326	genomic sequence information	299:326	genomic sequence information for the CA VI of pufferfish	299:354	In this study, genomic sequence information for the CA VI of pufferfish was used for molecular cloning.
29030255	0	32	theme	Takifugu	89:96	arg1	pufferfish					77:86	pufferfish	77:86	pufferfish (Takifugu rubripes)	77:106	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	0	32	theme	Takifugu	89:96	arg1	rubripes					98:105	Takifugu rubripes	89:105	Takifugu rubripes	89:105	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	4	33	theme	bp	405:406	arg1	sequence					413:420	a 1821 bp cDNA sequence	398:420	a 1821 bp cDNA sequence	398:420	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	7	34	theme	fish	960:963	arg1	sequences					971:979	mammalian and fish CA II sequences	946:979	mammalian and fish CA II sequences	946:979	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	13	35	theme	pufferfish	1789:1798	arg1	CA					1800:1801	the pufferfish CA	1785:1801	the pufferfish CA	1785:1801	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	3	36	theme	CA	336:337	arg1	pufferfish					345:354	the CA VI of pufferfish	332:354	the CA VI of pufferfish	332:354	In this study, genomic sequence information for the CA VI of pufferfish was used for molecular cloning.
29030255	12	37	dep	CA	1533:1534	arg1	VI					1536:1537	VI	1536:1537	VI	1536:1537	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	0	38	theme	Molecular	0:8	arg1	cloning					10:16	Molecular cloning	0:16	Molecular cloning	0:16	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	13	39	dep	in	1740:1741	arg1	situ					1743:1746	situ	1743:1746	situ	1743:1746	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	4	40	theme	1623bp	472:477	arg1	sequence					460:467	a complete coding sequence	442:467	a complete coding sequence of 1623bp	442:477	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	4	40	theme	1623bp	472:477	arg1	sequence					504:511	a deduced amino acid sequence	483:511	a deduced amino acid sequence of 540 amino acids from the open reading frame	483:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	1	41	dep	CA	132:133	arg1	VI					135:136	VI	135:136	VI	135:136	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	8	42	dep	sequence	1079:1086	arg1	VI					1076:1077	VI	1076:1077	VI	1076:1077	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	9	43	theme	potential	1095:1103	arg1	sites					1128:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	6	44	theme	%	706:706	arg1	identity					712:719	63%-77% identity	704:719	63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	704:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	7	45	theme	mammalian	946:954	arg1	sequences					971:979	mammalian and fish CA II sequences	946:979	mammalian and fish CA II sequences	946:979	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	7	46	theme	-37	927:929	arg1	%					926:926	%	926:926	%	926:926	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	9	47	theme	glycosylation	1114:1126	arg1	sites					1128:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	4	48	from	sequence	460:467	arg1	frame					554:558	the open reading frame	537:558	the open reading frame	537:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	3	49	theme	of	342:343	arg1	pufferfish					345:354	the CA VI of pufferfish	332:354	the CA VI of pufferfish	332:354	In this study, genomic sequence information for the CA VI of pufferfish was used for molecular cloning.
29030255	4	50	theme	complete	444:451	arg1	sequence					460:467	a complete coding sequence	442:467	a complete coding sequence of 1623bp	442:477	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	6	51	dep	sequences	748:756	arg1	zebrafish					759:767	zebrafish	759:767	zebrafish	759:767	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	51	dep	sequences	748:756	arg1	arowana					776:782	Asian arowana	770:782	Asian arowana	770:782	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	51	dep	sequences	748:756	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	51	dep	sequences	748:756	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	51	dep	sequences	748:756	arg1	salmon					785:790	salmon	785:790	salmon	785:790	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	7	52	theme	34	924:925	arg1	%					926:926	%	926:926	%	926:926	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	9	53	theme	cysteine	1142:1149	arg1	Cys-209					1172:1178	Cys-209	1172:1178	Cys-209	1172:1178	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	53	theme	cysteine	1142:1149	arg1	Cys-28					1161:1166	Cys-28	1161:1166	Cys-28	1161:1166	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	53	theme	cysteine	1142:1149	arg1	residues					1151:1158	two cysteine residues	1138:1158	two cysteine residues (Cys-28 and Cys-209)	1138:1179	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	2	54	theme	CA	243:244	arg1	occurrence					229:238	the occurrence	225:238	the occurrence of CA VI in pufferfish (Takifugu rubripes)	225:281	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	2	55	dep	CA	243:244	arg1	VI					246:247	VI	246:247	VI	246:247	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	4	56	theme	540	516:518	arg1	acids					526:530	540 amino acids	516:530	540 amino acids from the open reading frame	516:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	11	57	theme	characteristic	1452:1465	arg1	substitution					1475:1486	a characteristic Val/Ile substitution	1450:1486	a characteristic Val/Ile substitution at position 207	1450:1502	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	11	58	theme	site	1371:1374	arg1	analysis					1376:1383	Active site analysis	1364:1383	Active site analysis	1364:1383	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	6	59	theme	VI-like	740:746	arg1	zebrafish					759:767	zebrafish	759:767	zebrafish	759:767	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	59	theme	VI-like	740:746	arg1	arowana					776:782	Asian arowana	770:782	Asian arowana	770:782	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	59	theme	VI-like	740:746	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	59	theme	VI-like	740:746	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	59	theme	VI-like	740:746	arg1	salmon					785:790	salmon	785:790	salmon	785:790	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	4	60	theme	acids	526:530	arg1	sequence					460:467	a complete coding sequence	442:467	a complete coding sequence of 1623bp	442:477	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	4	60	theme	acids	526:530	arg1	sequence					504:511	a deduced amino acid sequence	483:511	a deduced amino acid sequence of 540 amino acids from the open reading frame	483:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	10	61	theme	phylogenetic	1272:1283	arg1	analyses					1285:1292	In silico and phylogenetic analyses	1258:1292	In silico and phylogenetic analyses	1258:1292	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	7	62	theme	CA	914:915	arg1	sequence					891:898	the protein sequence	879:898	the protein sequence of pufferfish CA VI	879:918	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	6	63	theme	fish	732:735	arg1	zebrafish					759:767	zebrafish	759:767	zebrafish	759:767	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	63	theme	fish	732:735	arg1	arowana					776:782	Asian arowana	770:782	Asian arowana	770:782	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	63	theme	fish	732:735	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	63	theme	fish	732:735	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	63	theme	fish	732:735	arg1	salmon					785:790	salmon	785:790	salmon	785:790	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	64	with	identity	712:719	arg1	zebrafish					759:767	zebrafish	759:767	zebrafish	759:767	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	64	with	identity	712:719	arg1	arowana					776:782	Asian arowana	770:782	Asian arowana	770:782	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	64	with	identity	712:719	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	64	with	identity	712:719	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	64	with	identity	712:719	arg1	salmon					785:790	salmon	785:790	salmon	785:790	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	4	65	theme	amino	493:497	arg1	sequence					504:511	a deduced amino acid sequence	483:511	a deduced amino acid sequence of 540 amino acids from the open reading frame	483:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	5	66	theme	BLAST	563:567	arg1	search					569:574	A BLAST search	561:574	A BLAST search	561:574	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	7	67	contain	has	920:922	arg2	identity					932:939	34%-37% identity	924:939	34%-37% identity with mammalian and fish CA II sequences	924:979	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	7	67	contain	has	920:922	arg1	sequence					891:898	the protein sequence	879:898	the protein sequence of pufferfish CA VI	879:918	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	12	68	theme	puffer	1526:1531	arg1	CA					1533:1534	puffer CA VI	1526:1537	puffer CA VI	1526:1537	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	10	69	theme	pufferfish	1308:1317	arg1	CA					1319:1320	pufferfish CA VI	1308:1323	pufferfish CA VI	1308:1323	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	10	69	theme	pufferfish	1308:1317	arg1	protein					1355:1361	an extracellular secretory protein	1328:1361	an extracellular secretory protein	1328:1361	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	11	70	theme	low-activity	1418:1429	arg1	isozymes					1434:1441	a low-activity CA isozymes	1416:1441	a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207	1416:1502	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	11	70	theme	low-activity	1418:1429	arg1	protein					1405:1411	this protein	1400:1411	this protein	1400:1411	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	7	71	theme	protein	883:889	arg1	sequence					891:898	the protein sequence	879:898	the protein sequence of pufferfish CA VI	879:918	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	13	72	theme	quantitative	1719:1730	arg1	PCR					1732:1734	quantitative PCR	1719:1734	quantitative PCR	1719:1734	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	0	73	theme	carbonic	52:59	arg1	anhydrase					61:69	secretory carbonic anhydrase VI	42:72	secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes)	42:106	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	6	74	theme	%	710:710	arg1	identity					712:719	63%-77% identity	704:719	63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	704:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	8	75	theme	signal	998:1003	arg1	peptide					1005:1011	An NH2-terminal signal peptide	982:1011	An NH2-terminal signal peptide of 18 amino acids in length	982:1039	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	10	76	theme	secretory	1345:1353	arg1	CA					1319:1320	pufferfish CA VI	1308:1323	pufferfish CA VI	1308:1323	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	10	76	theme	secretory	1345:1353	arg1	protein					1355:1361	an extracellular secretory protein	1328:1361	an extracellular secretory protein	1328:1361	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	13	77	theme	chain	1697:1701	arg1	reaction					1703:1710	Reverse transcription-polymerase chain reaction	1664:1710	Reverse transcription-polymerase chain reaction (PCR)	1664:1716	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	13	77	theme	chain	1697:1701	arg1	PCR					1713:1715	PCR	1713:1715	PCR	1713:1715	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	9	78	from	present	1229:1235	arg1	CA					1251:1252	pufferfish CA VI	1240:1255	pufferfish CA VI	1240:1255	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	7	79	with	identity	932:939	arg1	sequences					971:979	mammalian and fish CA II sequences	946:979	mammalian and fish CA II sequences	946:979	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	7	80	dep	CA	914:915	arg1	VI					917:918	VI	917:918	VI	917:918	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	7	81	theme	sequences	855:863	arg1	alignment					830:838	alignment	830:838	alignment of two or more sequences	830:863	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	2	82	theme	Takifugu	264:271	arg1	pufferfish					252:261	pufferfish	252:261	pufferfish (Takifugu rubripes)	252:281	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	2	82	theme	Takifugu	264:271	arg1	rubripes					273:280	Takifugu rubripes	264:280	Takifugu rubripes	264:280	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	1	83	theme	secretory	167:175	arg1	isozyme					177:183	a secretory isozyme	165:183	a secretory isozyme in mammals	165:194	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	1	83	theme	secretory	167:175	arg1	anhydrase					118:126	Carbonic anhydrase VI (CA VI)	109:137	Carbonic anhydrase VI (CA VI)	109:137	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	9	84	located	present	1229:1235	arg2	sites					1128:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	84	located	present	1229:1235	arg1	CA					1251:1252	pufferfish CA VI	1240:1255	pufferfish CA VI	1240:1255	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	84	located	present	1229:1235	arg2	Cys-28					1161:1166	Cys-28	1161:1166	Cys-28	1161:1166	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	84	located	present	1229:1235	arg2	Cys-209					1172:1178	Cys-209	1172:1178	Cys-209	1172:1178	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	84	located	present	1229:1235	arg2	residues					1151:1158	two cysteine residues	1138:1158	two cysteine residues (Cys-28 and Cys-209)	1138:1179	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	8	85	theme	amino	1019:1023	arg1	acids					1025:1029	18 amino acids	1016:1029	18 amino acids	1016:1029	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	4	86	theme	1821	400:403	arg1	bp					405:406	bp	405:406	bp	405:406	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	4	87	theme	reading	546:552	arg1	frame					554:558	the open reading frame	537:558	the open reading frame	537:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	12	88	theme	anhydrase	1599:1607	arg1	structure					1627:1635	a template structure	1616:1635	a template structure	1616:1635	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	12	88	theme	anhydrase	1599:1607	arg1	structure					1571:1579	the crystal structure	1559:1579	the crystal structure of human carbonic anhydrase XIV	1559:1611	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	1	89	theme	Carbonic	109:116	arg1	isozyme					177:183	a secretory isozyme	165:183	a secretory isozyme in mammals	165:194	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	1	89	theme	Carbonic	109:116	arg1	anhydrase					118:126	Carbonic anhydrase VI (CA VI)	109:137	Carbonic anhydrase VI (CA VI)	109:137	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	1	89	theme	Carbonic	109:116	arg1	CA					132:133	CA	132:133	CA	132:133	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	11	90	from	position	1491:1498	arg1	substitution					1475:1486	a characteristic Val/Ile substitution	1450:1486	a characteristic Val/Ile substitution at position 207	1450:1502	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	5	91	with	%	620:620	arg1	tilapia					652:658	tilapia	652:658	tilapia	652:658	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	5	91	with	%	620:620	arg1	human					645:649	human	645:649	human	645:649	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	5	91	with	%	620:620	arg1	CA					669:670	gar CA VI	665:673	gar CA VI	665:673	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	13	92	theme	liver	1829:1833	arg1	tissue					1835:1840	liver tissue	1829:1840	liver tissue	1829:1840	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	1	93	from	isozyme	177:183	arg1	mammals					188:194	mammals	188:194	mammals	188:194	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	9	94	theme	pufferfish	1240:1249	arg1	CA					1251:1252	pufferfish CA VI	1240:1255	pufferfish CA VI	1240:1255	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	2	95	from	CA	243:244	arg1	pufferfish					252:261	pufferfish	252:261	pufferfish (Takifugu rubripes)	252:281	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	2	95	from	CA	243:244	arg1	rubripes					273:280	Takifugu rubripes	264:280	Takifugu rubripes	264:280	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	5	96	theme	67	627:628	arg1	%					629:629	%	629:629	%	629:629	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	4	97	theme	open	541:544	arg1	frame					554:558	the open reading frame	537:558	the open reading frame	537:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	0	98	from	characterization	22:37	arg1	pufferfish					77:86	pufferfish	77:86	pufferfish (Takifugu rubripes)	77:106	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	0	98	from	characterization	22:37	arg1	rubripes					98:105	Takifugu rubripes	89:105	Takifugu rubripes	89:105	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	8	99	theme	pufferfish	1062:1071	arg1	sequence					1079:1086	the pufferfish CA VI sequence	1058:1086	the pufferfish CA VI sequence	1058:1086	An NH2-terminal signal peptide of 18 amino acids in length was predicted in the pufferfish CA VI sequence.
29030255	7	100	theme	II	968:969	arg1	sequences					971:979	mammalian and fish CA II sequences	946:979	mammalian and fish CA II sequences	946:979	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	12	101	theme	carbonic	1590:1597	arg1	anhydrase					1599:1607	human carbonic anhydrase XIV	1584:1611	human carbonic anhydrase XIV	1584:1611	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	0	102	from	anhydrase	61:69	arg1	pufferfish					77:86	pufferfish	77:86	pufferfish (Takifugu rubripes)	77:106	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	0	102	from	anhydrase	61:69	arg1	rubripes					98:105	Takifugu rubripes	89:105	Takifugu rubripes	89:105	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	6	103	theme	yellow	803:808	arg1	sequences					748:756	other fish CA VI-like sequences	726:756	other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker)	726:817	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	6	103	theme	yellow	803:808	arg1	croaker					810:816	large yellow croaker	797:816	large yellow croaker	797:816	It also shows 63%-77% identity with other fish CA VI-like sequences (zebrafish, Asian arowana, salmon, and large yellow croaker).
29030255	0	104	from	cloning	10:16	arg1	pufferfish					77:86	pufferfish	77:86	pufferfish (Takifugu rubripes)	77:106	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	0	104	from	cloning	10:16	arg1	rubripes					98:105	Takifugu rubripes	89:105	Takifugu rubripes	89:105	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	7	105	dep	identity	932:939	arg1	%					930:930	%	930:930	%	930:930	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	7	106	theme	CA	965:966	arg1	sequences					971:979	mammalian and fish CA II sequences	946:979	mammalian and fish CA II sequences	946:979	Moreover, alignment of two or more sequences revealed that the protein sequence of pufferfish CA VI has 34%-37% identity with mammalian and fish CA II sequences.
29030255	13	107	theme	PCR	1732:1734	arg1	results					1762:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results	1664:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results	1664:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	4	108	theme	cDNA	408:411	arg1	sequence					413:420	a 1821 bp cDNA sequence	398:420	a 1821 bp cDNA sequence	398:420	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	9	109	dep	CA	1251:1252	arg1	VI					1254:1255	VI	1254:1255	VI	1254:1255	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	3	110	theme	genomic	299:305	arg1	information					316:326	genomic sequence information	299:326	genomic sequence information for the CA VI of pufferfish	299:354	In this study, genomic sequence information for the CA VI of pufferfish was used for molecular cloning.
29030255	3	111	dep	pufferfish	345:354	arg1	VI					339:340	VI	339:340	VI	339:340	In this study, genomic sequence information for the CA VI of pufferfish was used for molecular cloning.
29030255	1	112	dep	anhydrase	118:126	arg1	VI					128:129	VI	128:129	VI	128:129	Carbonic anhydrase VI (CA VI) has been characterized as a secretory isozyme in mammals.
29030255	9	113	gly	glycosylation	1114:1126	arg2	sites					1128:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	113	gly	glycosylation	1114:1126	arg1	CA					1251:1252	pufferfish CA VI	1240:1255	pufferfish CA VI	1240:1255	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	113	gly	glycosylation	1114:1126	arg2	Three					1089:1093	Three	1089:1093	Three	1089:1093	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	3	114	theme	molecular	369:377	arg1	cloning					379:385	molecular cloning	369:385	molecular cloning	369:385	In this study, genomic sequence information for the CA VI of pufferfish was used for molecular cloning.
29030255	5	115	with	%	615:615	arg1	tilapia					652:658	tilapia	652:658	tilapia	652:658	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	5	115	with	%	615:615	arg1	human					645:649	human	645:649	human	645:649	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	5	115	with	%	615:615	arg1	CA					669:670	gar CA VI	665:673	gar CA VI	665:673	A BLAST search indicated that this protein exhibits 53%, 79%, and 67% identity with human, tilapia, and gar CA VI, respectively.
29030255	12	116	theme	CA	1533:1534	arg1	modeling					1514:1521	Homology modeling	1505:1521	Homology modeling of puffer CA VI	1505:1537	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	4	117	theme	deduced	485:491	arg1	sequence					504:511	a deduced amino acid sequence	483:511	a deduced amino acid sequence of 540 amino acids from the open reading frame	483:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	9	118	attach	present	1229:1235	arg2	sites					1128:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	118	attach	present	1229:1235	arg1	CA					1251:1252	pufferfish CA VI	1240:1255	pufferfish CA VI	1240:1255	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	118	attach	present	1229:1235	arg2	Cys-28					1161:1166	Cys-28	1161:1166	Cys-28	1161:1166	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	118	attach	present	1229:1235	arg2	Cys-209					1172:1178	Cys-209	1172:1178	Cys-209	1172:1178	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	9	118	attach	present	1229:1235	arg2	residues					1151:1158	two cysteine residues	1138:1158	two cysteine residues (Cys-28 and Cys-209)	1138:1179	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	11	119	theme	due	1443:1445	arg1	isozymes					1434:1441	a low-activity CA isozymes	1416:1441	a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207	1416:1502	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	11	119	theme	due	1443:1445	arg1	protein					1405:1411	this protein	1400:1411	this protein	1400:1411	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	0	120	theme	secretory	42:50	arg1	anhydrase					61:69	secretory carbonic anhydrase VI	42:72	secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes)	42:106	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	9	121	theme	N-linked	1105:1112	arg1	sites					1128:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	12	122	theme	template	1618:1625	arg1	structure					1627:1635	a template structure	1616:1635	a template structure	1616:1635	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	12	122	theme	template	1618:1625	arg1	structure					1571:1579	the crystal structure	1559:1579	the crystal structure of human carbonic anhydrase XIV	1559:1611	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	0	123	dep	anhydrase	61:69	arg1	VI					71:72	VI	71:72	VI	71:72	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	2	124	from	occurrence	229:238	arg1	pufferfish					252:261	pufferfish	252:261	pufferfish (Takifugu rubripes)	252:281	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	2	124	from	occurrence	229:238	arg1	rubripes					273:280	Takifugu rubripes	264:280	Takifugu rubripes	264:280	Our present study confirmed the occurrence of CA VI in pufferfish (Takifugu rubripes).
29030255	4	125	theme	coding	453:458	arg1	sequence					460:467	a complete coding sequence	442:467	a complete coding sequence of 1623bp	442:477	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	11	126	theme	CA	1431:1432	arg1	isozymes					1434:1441	a low-activity CA isozymes	1416:1441	a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207	1416:1502	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	11	126	theme	CA	1431:1432	arg1	protein					1405:1411	this protein	1400:1411	this protein	1400:1411	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	13	127	theme	hybridization	1748:1760	arg1	results					1762:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results	1664:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results	1664:1768	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	0	128	theme	anhydrase	61:69	arg1	characterization					22:37	characterization	22:37	characterization	22:37	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	0	128	theme	anhydrase	61:69	arg1	cloning					10:16	Molecular cloning	0:16	Molecular cloning	0:16	Molecular cloning and characterization of secretory carbonic anhydrase VI in pufferfish (Takifugu rubripes).
29030255	12	129	theme	human	1584:1588	arg1	anhydrase					1599:1607	human carbonic anhydrase XIV	1584:1611	human carbonic anhydrase XIV	1584:1611	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	10	130	theme	In	1258:1259	arg1	analyses					1285:1292	In silico and phylogenetic analyses	1258:1292	In silico and phylogenetic analyses	1258:1292	In silico and phylogenetic analyses revealed that pufferfish CA VI is an extracellular secretory protein.
29030255	11	131	theme	Val/Ile	1467:1473	arg1	substitution					1475:1486	a characteristic Val/Ile substitution	1450:1486	a characteristic Val/Ile substitution at position 207	1450:1502	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	3	132	used	used	360:363	arg2	information					316:326	genomic sequence information	299:326	genomic sequence information for the CA VI of pufferfish	299:354	In this study, genomic sequence information for the CA VI of pufferfish was used for molecular cloning.
29030255	12	133	theme	crystal	1563:1569	arg1	structure					1627:1635	a template structure	1616:1635	a template structure	1616:1635	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	12	133	theme	crystal	1563:1569	arg1	structure					1571:1579	the crystal structure	1559:1579	the crystal structure of human carbonic anhydrase XIV	1559:1611	Homology modeling of puffer CA VI was performed using the crystal structure of human carbonic anhydrase XIV as a template structure, based on high similarity.
29030255	4	134	theme	amino	520:524	arg1	acids					526:530	540 amino acids	516:530	540 amino acids from the open reading frame	516:558	We cloned a 1821 bp cDNA sequence, which consisted of a complete coding sequence of 1623bp and a deduced amino acid sequence of 540 amino acids from the open reading frame.
29030255	11	135	theme	Active	1364:1369	arg1	analysis					1376:1383	Active site analysis	1364:1383	Active site analysis	1364:1383	Active site analysis indicated that this protein is a low-activity CA isozymes due to a characteristic Val/Ile substitution at position 207.
29030255	13	136	dep	expressed	1816:1824	arg1	VI					1803:1804	VI	1803:1804	VI	1803:1804	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29030255	9	137	link	N-linked	1105:1112	arg1	sites					1128:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites	1089:1132	Three potential N-linked glycosylation sites and two cysteine residues (Cys-28 and Cys-209) that are likely to form one disulfide bond were present in pufferfish CA VI.
29030255	13	138	theme	in	1740:1741	arg1	hybridization					1748:1760	in situ hybridization	1740:1760	in situ hybridization	1740:1760	Reverse transcription-polymerase chain reaction (PCR), quantitative PCR and in situ hybridization results revealed that, the pufferfish CA VI is highly expressed in liver tissue.
29491151	7	0	theme	infectivity	1482:1492	arg1	titer					1494:1498	a higher infectivity titer	1473:1498	a higher infectivity titer	1473:1498	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	2	1	theme	envelope	603:610	arg1	glycoproteins					612:624	250 patient-derived gp120 envelope glycoproteins	577:624	250 patient-derived gp120 envelope glycoproteins	577:624	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	1	2	theme	HIV	268:270	arg1	infection					272:280	HIV infection	268:280	HIV infection	268:280	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	2	3	theme	patient-derived	581:595	arg1	glycoproteins					612:624	250 patient-derived gp120 envelope glycoproteins	577:624	250 patient-derived gp120 envelope glycoproteins	577:624	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	10	4	theme	infectious	2293:2302	arg1	fitness					2304:2310	the unique infectious fitness	2282:2310	the unique infectious fitness of the virus	2282:2323	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	6	5	theme	viral	1284:1288	arg1	clones					1290:1295	the viral clones	1280:1295	the viral clones	1280:1295	Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants.
29491151	12	6	theme	long	2548:2551	arg1	way					2553:2555	a long way	2546:2555	a long way toward helping with the design of an effective vaccine against HIV	2546:2622	An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV.
29491151	7	7	theme	reduced	1411:1417	arg1	number					1419:1424	a reduced number	1409:1424	a reduced number of potential N-linked glycosylation sites	1409:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	7	7	theme	reduced	1411:1417	arg1	regions					1400:1406	shorter V1V2 regions	1387:1406	shorter V1V2 regions	1387:1406	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	9	8	theme	variants	1749:1756	arg1	sensitivity					1727:1737	The sensitivity	1723:1737	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121)	1723:1860	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	8	theme	variants	1749:1756	arg1	lower					1883:1887	lower	1883:1887	lower	1883:1887	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	8	9	theme	chimeric	1675:1682	arg1	viruses					1684:1690	all 65 chimeric viruses	1668:1690	all 65 chimeric viruses	1668:1690	CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses.
29491151	7	10	theme	glycosylation	1448:1460	arg1	sites					1462:1466	potential N-linked glycosylation sites	1429:1466	potential N-linked glycosylation sites	1429:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	12	11	theme	salient	2504:2510	arg1	features					2512:2519	the salient features	2500:2519	the salient features of the TF virus	2500:2535	An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV.
29491151	9	12	theme	HIV	2058:2060	arg1	research					2062:2069	HIV research	2058:2069	HIV research	2058:2069	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	6	13	theme	phenotypic	1257:1266	arg1	analysis					1268:1275	genotypic and phenotypic analysis	1243:1275	genotypic and phenotypic analysis of the viral clones	1243:1295	Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants.
29491151	13	14	attach	isolated	2699:2706	arg2	viruses					2691:2697	recently transmitted viruses	2670:2697	recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host	2670:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	13	14	attach	isolated	2699:2706	arg1	infants					2713:2719	infants	2713:2719	infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host	2713:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	1	15	theme	molecular	195:203	arg1	composition					220:230	the precise molecular and biological composition	183:230	the precise molecular and biological composition of the viral strains that establish HIV infection in the human host	183:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	10	16	theme	vaccine	2200:2206	arg1	research					2208:2215	vaccine research	2200:2215	vaccine research	2200:2215	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	7	17	theme	V1V2	1395:1398	arg1	number					1419:1424	a reduced number	1409:1424	a reduced number of potential N-linked glycosylation sites	1409:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	7	17	theme	V1V2	1395:1398	arg1	regions					1400:1406	shorter V1V2 regions	1387:1406	shorter V1V2 regions	1387:1406	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	0	18	theme	Coreceptor	116:125	arg1	Use					103:105	Use	103:105	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.	0:157	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	1	19	theme	biological	209:218	arg1	composition					220:230	the precise molecular and biological composition	183:230	the precise molecular and biological composition of the viral strains that establish HIV infection in the human host	183:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	10	20	theme	research	2150:2157	arg1	areas					2137:2141	the frontier areas	2124:2141	the frontier areas of HIV research	2124:2157	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	5	21	theme	neutralizing	1209:1220	arg1	antibodies					1222:1231	broadly neutralizing antibodies	1201:1231	broadly neutralizing antibodies	1201:1231	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	5	22	theme	molecular	1071:1079	arg1	features					1081:1088	molecular features	1071:1088	molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies	1071:1231	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	3	23	theme	mother-to-child	787:801	arg1	transmission					803:814	mother-to-child transmission	787:814	mother-to-child transmission (MTCT)	787:821	Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection.
29491151	3	23	theme	mother-to-child	787:801	arg1	MTCT					817:820	MTCT	817:820	MTCT	817:820	Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection.
29491151	6	24	theme	TF	1315:1316	arg1	viruses					1318:1324	10 TF viruses	1312:1324	10 TF viruses from the eight infants	1312:1347	Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants.
29491151	10	25	theme	HIV	2146:2148	arg1	research					2150:2157	HIV research	2146:2157	HIV research	2146:2157	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	2	26	theme	transmitted	556:566	arg1	viruses					568:574	the early transmitted viruses	546:574	the early transmitted viruses	546:574	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	11	27	theme	transmitted	2415:2425	arg1	virus					2440:2444	transmitted founder [TF] virus	2415:2444	the virus that establishes successful infection (transmitted founder [TF] virus)	2366:2445	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	7	28	theme	TF	1354:1355	arg1	viruses					1357:1363	The TF viruses	1350:1363	The TF viruses	1350:1363	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	13	29	theme	transmitted	2679:2689	arg1	viruses					2691:2697	recently transmitted viruses	2670:2697	recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host	2670:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	11	30	dep	virus	2370:2374	arg1	virus					2440:2444	transmitted founder [TF] virus	2415:2444	the virus that establishes successful infection (transmitted founder [TF] virus)	2366:2445	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	2	31	theme	TF	505:506	arg1	virus					508:512	the TF virus	501:512	the TF virus	501:512	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	0	32	theme	C	72:72	arg1	gp120					96:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	5	33	theme	per-infectious-particle	1107:1129	arg1	infectivity					1131:1141	per-infectious-particle infectivity	1107:1141	per-infectious-particle infectivity	1107:1141	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	5	34	theme	sensitivity	1186:1196	arg1	features					1081:1088	molecular features	1071:1088	molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies	1071:1231	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	13	35	theme	viruses	2691:2697	arg1	properties					2656:2665	the biological properties	2641:2665	the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host	2641:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	0	36	theme	Glycoprotein	83:94	arg1	gp120					96:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	1	37	theme	HIV	353:355	arg1	infection					357:365	HIV infection	353:365	HIV infection	353:365	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	7	38	theme	chronic	1554:1560	arg1	stage					1562:1566	the chronic stage	1550:1566	the chronic stage of infection	1550:1579	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	10	39	theme	HIV-1	2272:2276	arg1	diversity					2259:2267	the enormous genetic diversity	2238:2267	the enormous genetic diversity of HIV-1	2238:2276	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	10	39	theme	HIV-1	2272:2276	arg1	fitness					2304:2310	the unique infectious fitness	2282:2310	the unique infectious fitness of the virus	2282:2323	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	3	40	theme	infection	925:933	arg1	stage					916:920	the chronic stage	904:920	the chronic stage of infection	904:933	Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection.
29491151	13	41	theme	TF	2815:2816	arg1	virus					2818:2822	the TF virus	2811:2822	the TF virus that establishes infection in the human host	2811:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	4	42	theme	chimeric	968:975	arg1	viruses					977:983	65 chimeric viruses	965:983	65 chimeric viruses	965:983	Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C.
29491151	2	43	theme	transmitted	398:408	arg1	virus					423:427	the transmitted founder (TF) virus	394:427	the transmitted founder (TF) virus	394:427	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	5	44	theme	envelope	1097:1104	arg1	features					1081:1088	molecular features	1071:1088	molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies	1071:1231	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	10	45	theme	virus	2319:2323	arg1	diversity					2259:2267	the enormous genetic diversity	2238:2267	the enormous genetic diversity of HIV-1	2238:2276	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	10	45	theme	virus	2319:2323	arg1	fitness					2304:2310	the unique infectious fitness	2282:2310	the unique infectious fitness of the virus	2282:2323	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	7	46	gly	glycosylation	1448:1460	arg2	sites					1462:1466	potential N-linked glycosylation sites	1429:1466	potential N-linked glycosylation sites	1429:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	4	47	theme	subtype	1028:1034	arg1	C					1036:1036	HIV-1 subtype C	1022:1036	HIV-1 subtype C	1022:1036	Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C.
29491151	11	48	theme	viral	2350:2354	arg1	variants					2356:2363	viral variants	2350:2363	viral variants	2350:2363	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	10	49	theme	frontier	2128:2135	arg1	areas					2137:2141	the frontier areas	2124:2141	the frontier areas of HIV research	2124:2157	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	0	50	theme	Unique	0:5	arg1	Characteristics					18:32	Unique Phenotypic Characteristics	0:32	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.	0:157	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	9	51	theme	chronic	1944:1950	arg1	stage					1952:1956	the chronic stage	1940:1956	the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist	1940:2114	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	6	52	from	infants	1341:1347	arg1	viruses					1318:1324	10 TF viruses	1312:1324	10 TF viruses from the eight infants	1312:1347	Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants.
29491151	10	53	theme	unique	2286:2291	arg1	fitness					2304:2310	the unique infectious fitness	2282:2310	the unique infectious fitness of the virus	2282:2323	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	2	54	theme	infectious	477:486	arg1	potential					488:496	infectious potential	477:496	infectious potential	477:496	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	5	55	theme	tropism	1155:1161	arg1	features					1081:1088	molecular features	1071:1088	molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies	1071:1231	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	7	56	theme	virus	1516:1520	arg1	variants					1522:1529	the virus variants	1512:1529	the virus variants from the adults in the chronic stage of infection	1512:1579	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	9	57	theme	standard	1777:1784	arg1	panel					1786:1790	a standard panel	1775:1790	a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121)	1775:1860	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	58	theme	Tremendous	1982:1991	arg1	progress					1993:2000	infection.IMPORTANCE Tremendous progress	1961:2000	infection.IMPORTANCE Tremendous progress	1961:2000	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	0	59	theme	HIV-1	58:62	arg1	gp120					96:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	5	60	theme	drug	1164:1167	arg1	sensitivity					1169:1179	drug sensitivity	1164:1179	drug sensitivity	1164:1179	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	1	61	theme	immunization	332:343	arg1	means					323:327	effective means	313:327	effective means of immunization against HIV infection	313:365	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	2	62	link	patient-derived	581:595	arg1	glycoproteins					612:624	250 patient-derived gp120 envelope glycoproteins	577:624	250 patient-derived gp120 envelope glycoproteins	577:624	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	0	63	dep	Characteristics	18:32	arg1	Use					103:105	Use	103:105	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.	0:157	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	13	64	from	infection	2841:2849	arg1	host					2864:2867	the human host	2854:2867	the human host	2854:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	9	65	theme	monoclonal	1808:1817	arg1	antibodies					1819:1828	monoclonal antibodies	1808:1828	neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121)	1795:1860	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	65	theme	monoclonal	1808:1817	arg1	PG16					1844:1847	PG16	1844:1847	PG16	1844:1847	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	65	theme	monoclonal	1808:1817	arg1	PGT121					1854:1859	PGT121	1854:1859	PGT121	1854:1859	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	8	66	theme	CXCR6	1582:1586	arg1	usage					1599:1603	CXCR6 coreceptor usage	1582:1603	CXCR6 coreceptor usage	1582:1603	CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses.
29491151	8	67	used	used	1660:1663	arg2	usage					1599:1603	CXCR6 coreceptor usage	1582:1603	CXCR6 coreceptor usage	1582:1603	CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses.
29491151	8	68	theme	CCR5	1633:1636	arg1	coreceptor					1638:1647	the CCR5 coreceptor	1629:1647	the CCR5 coreceptor	1629:1647	CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses.
29491151	1	69	theme	strains	245:251	arg1	composition					220:230	the precise molecular and biological composition	183:230	the precise molecular and biological composition of the viral strains that establish HIV infection in the human host	183:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	10	70	dep	research	2208:2215	arg1	diversity					2259:2267	the enormous genetic diversity	2238:2267	the enormous genetic diversity of HIV-1	2238:2276	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	10	70	dep	research	2208:2215	arg1	fitness					2304:2310	the unique infectious fitness	2282:2310	the unique infectious fitness of the virus	2282:2323	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	7	71	theme	higher	1475:1480	arg1	titer					1494:1498	a higher infectivity titer	1473:1498	a higher infectivity titer	1473:1498	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	11	72	theme	[TF	2435:2437	arg1	virus					2440:2444	transmitted founder [TF] virus	2415:2444	the virus that establishes successful infection (transmitted founder [TF] virus)	2366:2445	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	2	73	theme	gp120	597:601	arg1	glycoproteins					612:624	250 patient-derived gp120 envelope glycoproteins	577:624	250 patient-derived gp120 envelope glycoproteins	577:624	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	6	74	theme	clones	1290:1295	arg1	analysis					1268:1275	genotypic and phenotypic analysis	1243:1275	genotypic and phenotypic analysis of the viral clones	1243:1295	Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants.
29491151	12	75	theme	vaccine	2604:2610	arg1	design					2581:2586	the design	2577:2586	the design of an effective vaccine against HIV	2577:2622	An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV.
29491151	7	76	theme	sites	1462:1466	arg1	number					1419:1424	a reduced number	1409:1424	a reduced number of potential N-linked glycosylation sites	1409:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	7	76	theme	sites	1462:1466	arg1	regions					1400:1406	shorter V1V2 regions	1387:1406	shorter V1V2 regions	1387:1406	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	7	77	theme	potential	1429:1437	arg1	sites					1462:1466	potential N-linked glycosylation sites	1429:1466	potential N-linked glycosylation sites	1429:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	7	78	link	N-linked	1439:1446	arg1	sites					1462:1466	potential N-linked glycosylation sites	1429:1466	potential N-linked glycosylation sites	1429:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	9	79	theme	half	2042:2045	arg1	decades					2047:2053	the last three and half decades	2023:2053	decades	2047:2053	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	1	80	theme	precise	187:193	arg1	composition					220:230	the precise molecular and biological composition	183:230	the precise molecular and biological composition of the viral strains that establish HIV infection in the human host	183:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	2	81	theme	biological	451:460	arg1	properties					462:471	biological properties	451:471	biological properties	451:471	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	7	82	theme	N-linked	1439:1446	arg1	sites					1462:1466	potential N-linked glycosylation sites	1429:1466	potential N-linked glycosylation sites	1429:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	2	83	gly	glycoproteins	612:624	arg1	glycoproteins					612:624	250 patient-derived gp120 envelope glycoproteins	577:624	250 patient-derived gp120 envelope glycoproteins	577:624	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	12	84	theme	virus	2531:2535	arg1	features					2512:2519	the salient features	2500:2519	the salient features of the TF virus	2500:2535	An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV.
29491151	9	85	theme	research	2062:2069	arg1	three					2032:2036	three	2032:2036	three	2032:2036	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	85	theme	research	2062:2069	arg1	research					2062:2069	HIV research	2058:2069	HIV research	2058:2069	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	86	theme	virus	1906:1910	arg1	variants					1912:1919	the virus variants	1902:1919	the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist	1902:2114	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	12	87	theme	TF	2528:2529	arg1	virus					2531:2535	the TF virus	2524:2535	the TF virus	2524:2535	An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV.
29491151	0	88	theme	Founder	142:148	arg1	Viruses					150:156	Transmitted Founder Viruses	130:156	Transmitted Founder Viruses	130:156	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	7	89	theme	shorter	1387:1393	arg1	number					1419:1424	a reduced number	1409:1424	a reduced number of potential N-linked glycosylation sites	1409:1466	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	7	89	theme	shorter	1387:1393	arg1	regions					1400:1406	shorter V1V2 regions	1387:1406	shorter V1V2 regions	1387:1406	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	9	90	theme	significant	2081:2091	arg1	gaps					2093:2096	some significant gaps	2076:2096	some significant gaps	2076:2096	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	13	91	theme	human	2858:2862	arg1	host					2864:2867	the human host	2854:2867	the human host	2854:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	2	92	theme	viruses	568:574	arg1	population					532:541	the population	528:541	the population of the early transmitted viruses	528:574	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	9	93	dep	antibodies	1819:1828	arg1	antibodies					1819:1828	monoclonal antibodies	1808:1828	neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121)	1795:1860	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	93	dep	antibodies	1819:1828	arg1	PG16					1844:1847	PG16	1844:1847	PG16	1844:1847	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	93	dep	antibodies	1819:1828	arg1	PGT121					1854:1859	PGT121	1854:1859	PGT121	1854:1859	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	7	94	theme	infection	1571:1579	arg1	stage					1562:1566	the chronic stage	1550:1566	the chronic stage of infection	1550:1579	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	11	95	theme	successful	2393:2402	arg1	infection					2404:2412	successful infection	2393:2412	successful infection	2393:2412	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	0	96	theme	Envelope	74:81	arg1	gp120					96:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	3	97	theme	heterosexual	873:884	arg1	route					886:890	the heterosexual route	869:890	the heterosexual route	869:890	Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection.
29491151	0	98	theme	gp120	96:100	arg1	Characteristics					18:32	Unique Phenotypic Characteristics	0:32	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.	0:157	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	5	99	theme	infectivity	1131:1141	arg1	features					1081:1088	molecular features	1071:1088	molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies	1071:1231	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	2	100	dep	properties	462:471	arg1	the					447:449	the	447:449	the	447:449	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	13	101	theme	biological	2645:2654	arg1	properties					2656:2665	the biological properties	2641:2665	the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host	2641:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	1	102	theme	Adequate	159:166	arg1	information					168:178	Adequate information	159:178	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host	159:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	3	103	theme	chronic	908:914	arg1	stage					916:920	the chronic stage	904:920	the chronic stage of infection	904:933	Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection.
29491151	10	104	theme	enormous	2242:2249	arg1	diversity					2259:2267	the enormous genetic diversity	2238:2267	the enormous genetic diversity of HIV-1	2238:2276	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	2	105	theme	chimeric	678:685	arg1	viruses					687:693	chimeric viruses	678:693	chimeric viruses	678:693	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	10	106	theme	genetic	2251:2257	arg1	diversity					2259:2267	the enormous genetic diversity	2238:2267	the enormous genetic diversity of HIV-1	2238:2276	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	5	107	theme	coreceptor	1144:1153	arg1	tropism					1155:1161	coreceptor tropism	1144:1161	coreceptor tropism	1144:1161	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	1	108	from	information	168:178	arg1	composition					220:230	the precise molecular and biological composition	183:230	the precise molecular and biological composition of the viral strains that establish HIV infection in the human host	183:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	2	109	dep	obtain	671:676	arg1	pMN-K7-Luc-IRESs-NefΔgp120					641:666	pMN-K7-Luc-IRESs-NefΔgp120	641:666	pMN-K7-Luc-IRESs-NefΔgp120	641:666	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	11	110	theme	variants	2356:2363	arg1	repertoire					2336:2345	the repertoire	2332:2345	the repertoire of viral variants	2332:2363	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	11	110	theme	variants	2356:2363	arg1	variants					2356:2363	viral variants	2350:2363	viral variants	2350:2363	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	0	111	theme	CXCR6	110:114	arg1	Coreceptor					116:125	CXCR6 Coreceptor	110:125	CXCR6 Coreceptor	110:125	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	2	112	theme	virus	508:512	arg1	properties					462:471	biological properties	451:471	biological properties	451:471	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	2	112	theme	virus	508:512	arg1	potential					488:496	infectious potential	477:496	infectious potential	477:496	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	10	113	theme	areas	2137:2141	arg1	One					2117:2119	One	2117:2119	One	2117:2119	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	10	113	theme	areas	2137:2141	arg1	areas					2137:2141	the frontier areas	2124:2141	the frontier areas of HIV research	2124:2157	One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus.
29491151	0	114	theme	Phenotypic	7:16	arg1	Characteristics					18:32	Unique Phenotypic Characteristics	0:32	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.	0:157	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	12	115	theme	effective	2594:2602	arg1	vaccine					2604:2610	an effective vaccine	2591:2610	an effective vaccine against HIV	2591:2622	An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV.
29491151	4	116	theme	HIV-1	1022:1026	arg1	C					1036:1036	HIV-1 subtype C	1022:1036	HIV-1 subtype C	1022:1036	Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C.
29491151	1	117	theme	human	289:293	arg1	host					295:298	the human host	285:298	the human host	285:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	7	118	from	adults	1540:1545	arg1	variants					1522:1529	the virus variants	1512:1529	the virus variants from the adults in the chronic stage of infection	1512:1579	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	7	118	from	adults	1540:1545	arg1	stage					1562:1566	the chronic stage	1550:1566	the chronic stage of infection	1550:1579	The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection.
29491151	0	119	theme	Transmitted	46:56	arg1	gp120					96:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	9	120	theme	infection.IMPORTANCE	1961:1980	arg1	progress					1993:2000	infection.IMPORTANCE Tremendous progress	1961:2000	infection.IMPORTANCE Tremendous progress	1961:2000	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	2	121	theme	founder	410:416	arg1	virus					423:427	the transmitted founder (TF) virus	394:427	the transmitted founder (TF) virus	394:427	In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses.
29491151	0	122	theme	Subtype	64:70	arg1	gp120					96:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120	37:100	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	1	123	theme	effective	313:321	arg1	means					323:327	effective means	313:327	effective means of immunization against HIV infection	313:365	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	13	124	theme	unique	2782:2787	arg1	characterizations					2789:2805	unique characterizations	2782:2805	unique characterizations for the TF virus that establishes infection in the human host	2782:2867	Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.
29491151	0	125	theme	Transmitted	130:140	arg1	Viruses					150:156	Transmitted Founder Viruses	130:156	Transmitted Founder Viruses	130:156	Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses.
29491151	5	126	theme	sensitivity	1169:1179	arg1	features					1081:1088	molecular features	1071:1088	molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies	1071:1231	The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies.
29491151	6	127	theme	genotypic	1243:1251	arg1	analysis					1268:1275	genotypic and phenotypic analysis	1243:1275	genotypic and phenotypic analysis of the viral clones	1243:1295	Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants.
29491151	9	128	from	adults	1930:1935	arg1	stage					1952:1956	the chronic stage	1940:1956	the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist	1940:2114	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	128	from	adults	1930:1935	arg1	variants					1912:1919	the virus variants	1902:1919	the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist	1902:2114	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	129	theme	neutralizing	1795:1806	arg1	antibodies					1819:1828	monoclonal antibodies	1808:1828	neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121)	1795:1860	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	129	theme	neutralizing	1795:1806	arg1	PG16					1844:1847	PG16	1844:1847	PG16	1844:1847	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	129	theme	neutralizing	1795:1806	arg1	PGT121					1854:1859	PGT121	1854:1859	PGT121	1854:1859	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	8	130	theme	coreceptor	1588:1597	arg1	usage					1599:1603	CXCR6 coreceptor usage	1582:1603	CXCR6 coreceptor usage	1582:1603	CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses.
29491151	1	131	theme	viral	239:243	arg1	strains					245:251	the viral strains	235:251	the viral strains that establish HIV infection in the human host	235:298	Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection.
29491151	9	132	theme	antibodies	1819:1828	arg1	maraviroc					1761:1769	maraviroc	1761:1769	maraviroc	1761:1769	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	9	132	theme	antibodies	1819:1828	arg1	panel					1786:1790	a standard panel	1775:1790	a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121)	1775:1860	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
29491151	11	133	theme	founder	2427:2433	arg1	virus					2440:2444	transmitted founder [TF] virus	2415:2444	the virus that establishes successful infection (transmitted founder [TF] virus)	2366:2445	Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet.
29491151	9	134	theme	TF	1746:1747	arg1	variants					1749:1756	the TF variants	1742:1756	the TF variants	1742:1756	The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist.
28734139	0	0	theme	northern	61:68	arg1	Greece					70:75	northern Greece	61:75	northern Greece	61:75	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	4	1	theme	Virus	458:462	arg1	samples					464:470	Virus samples	458:470	Virus samples	458:470	Virus samples originated from vaccinated and unvaccinated patients, obtained at the National Influenza Centre for northern Greece.
28734139	10	2	theme	N-linked	1539:1546	arg1	sites					1562:1566	N-linked glycosylation sites	1539:1566	N-linked glycosylation sites	1539:1566	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	10	2	theme	N-linked	1539:1546	arg1	virus					1575:1579	the virus	1571:1579	the virus	1571:1579	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	11	3	from	antigenicity	1677:1688	arg1	effectiveness					1753:1765	vaccine effectiveness	1745:1765	vaccine effectiveness	1745:1765	Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.
28734139	4	4	theme	Influenza	551:559	arg1	Centre					561:566	the National Influenza Centre	538:566	the National Influenza Centre for northern Greece	538:586	Virus samples originated from vaccinated and unvaccinated patients, obtained at the National Influenza Centre for northern Greece.
28734139	5	5	dep	virus	683:687	arg1	Kong/4801/2014					696:709	Kong/4801/2014	696:709	Kong/4801/2014	696:709	Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed.
28734139	11	6	theme	Further	1633:1639	arg1	studies					1641:1647	Further studies	1633:1647	Further studies	1633:1647	Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.
28734139	5	7	theme	haemagglutinin	633:646	arg1	gene					648:651	the haemagglutinin gene	629:651	the haemagglutinin gene of the viruses	629:666	Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed.
28734139	3	8	located	detected	425:432	arg1	patients					448:455	vaccinated patients	437:455	vaccinated patients	437:455	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	3	8	located	detected	425:432	arg2	viruses					405:411	A(H3N2) circulating viruses	385:411	A(H3N2) circulating viruses	385:411	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	1	9	theme	influenza	128:136	arg1	season					148:153	the influenza 2016/2017 season	124:153	the influenza 2016/2017 season	124:153	Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification.
28734139	4	10	theme	National	542:549	arg1	Centre					561:566	the National Influenza Centre	538:566	the National Influenza Centre for northern Greece	538:586	Virus samples originated from vaccinated and unvaccinated patients, obtained at the National Influenza Centre for northern Greece.
28734139	10	11	theme	virus	1575:1579	arg1	sites					1562:1566	N-linked glycosylation sites	1539:1566	N-linked glycosylation sites	1539:1566	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	10	11	theme	virus	1575:1579	arg1	virus					1575:1579	the virus	1571:1579	the virus	1571:1579	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	5	12	theme	gene	648:651	arg1	comparison					615:624	comparison	615:624	comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014	615:709	Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed.
28734139	5	12	theme	gene	648:651	arg1	analysis					602:609	Phylogenetic analysis	589:609	Phylogenetic analysis	589:609	Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed.
28734139	7	13	theme	distinct	935:942	arg1	subcluster					944:953	a distinct subcluster	933:953	a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin	933:1070	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	3	14	theme	study	329:333	arg1	scope					316:320	The scope	312:320	The scope of the study	312:333	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	6	15	theme	clade	789:793	arg1	3C.2a					795:799	the genetic clade 3C.2a	777:799	the genetic clade 3C.2a	777:799	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	10	16	theme	viral	1613:1617	arg1	antigenicity					1619:1630	viral antigenicity	1613:1630	viral antigenicity	1613:1630	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	0	17	from	variants	26:33	arg1	patients					49:56	vaccinated patients	38:56	vaccinated patients in northern Greece	38:75	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	5	18	theme	Phylogenetic	589:600	arg1	analysis					602:609	Phylogenetic analysis	589:609	Phylogenetic analysis	589:609	Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed.
28734139	2	19	theme	2016/17	256:262	arg1	season					264:269	the 2016/17 season	252:269	the 2016/17 season in Greece	252:279	A high vaccination failure rate was noticed during the 2016/17 season in Greece, especially among the elderly.
28734139	1	20	theme	2016/2017	138:146	arg1	season					148:153	the influenza 2016/2017 season	124:153	the influenza 2016/2017 season	124:153	Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification.
28734139	10	21	theme	sites	1562:1566	arg1	losses					1529:1534	losses	1529:1534	losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity	1529:1630	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	9	22	theme	northern	1394:1401	arg1	Greece					1403:1408	northern Greece	1394:1408	northern Greece	1394:1408	However, viruses belonging to a specific 3C.2a1 subcluster was extensively circulating in northern Greece and among vaccinated individuals.
28734139	7	23	theme	vaccinated	903:912	arg1	patients					914:921	vaccinated patients	903:921	vaccinated patients	903:921	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	24	theme	3C.2a1	966:971	arg1	subclade					973:980	the 3C.2a1 subclade	962:980	the 3C.2a1 subclade	962:980	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	3	25	theme	circulating	393:403	arg1	viruses					405:411	A(H3N2) circulating viruses	385:411	A(H3N2) circulating viruses	385:411	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	0	26	theme	A	10:10	arg1	variants					26:33	Ιnfluenza A(H3N2) genetic variants	0:33	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece	0:75	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	10	27	theme	glycosylation	1548:1560	arg1	sites					1562:1566	N-linked glycosylation sites	1539:1566	N-linked glycosylation sites	1539:1566	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	10	27	theme	glycosylation	1548:1560	arg1	virus					1575:1579	the virus	1571:1579	the virus	1571:1579	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	7	28	theme	amino	1013:1017	arg1	substitutions					1024:1036	the amino acid substitutions	1009:1036	the amino acid substitutions N122D and T135K in haemagglutinin	1009:1070	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	28	theme	amino	1013:1017	arg1	T135K					1048:1052	T135K	1048:1052	T135K	1048:1052	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	28	theme	amino	1013:1017	arg1	N122D					1038:1042	N122D	1038:1042	N122D	1038:1042	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	0	29	theme	Ιnfluenza	0:8	arg1	H3N2					12:15	H3N2	12:15	H3N2	12:15	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	0	29	theme	Ιnfluenza	0:8	arg1	A					10:10	Ιnfluenza A	0:10	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece	0:75	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	10	30	gly	glycosylation	1548:1560	arg2	virus					1575:1579	the virus	1571:1579	the virus	1571:1579	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	10	30	gly	glycosylation	1548:1560	arg2	sites					1562:1566	N-linked glycosylation sites	1539:1566	N-linked glycosylation sites	1539:1566	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	10	30	gly	glycosylation	1548:1560	arg1	virus					1575:1579	the virus	1571:1579	the virus	1571:1579	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	5	31	theme	vaccine	675:681	arg1	virus					683:687	the vaccine virus A/Hong Kong/4801/2014	671:709	the vaccine virus A/Hong Kong/4801/2014	671:709	Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed.
28734139	6	32	theme	genetic	781:787	arg1	3C.2a					795:799	the genetic clade 3C.2a	777:799	the genetic clade 3C.2a	777:799	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	1	33	theme	Influenza	78:86	arg1	H3N2					90:93	H3N2	90:93	H3N2	90:93	Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification.
28734139	1	33	theme	Influenza	78:86	arg1	A					88:88	Influenza A	78:88	Influenza A(H3N2) viruses	78:102	Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification.
28734139	3	34	theme	viruses	417:423	arg1	characteristics					366:380	the genetic characteristics	354:380	the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients	354:455	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	7	35	located	detected	891:898	arg2	viruses					883:889	viruses	883:889	viruses detected in vaccinated patients	883:921	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	35	located	detected	891:898	arg1	patients					914:921	vaccinated patients	903:921	vaccinated patients	903:921	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	11	36	theme	variant	1698:1704	arg1	strain					1706:1711	this variant strain	1693:1711	this variant strain	1693:1711	Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.
28734139	1	37	theme	A	88:88	arg1	viruses					96:102	Influenza A(H3N2) viruses	78:102	Influenza A(H3N2) viruses	78:102	Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification.
28734139	1	38	theme	genetic	176:182	arg1	diversification					184:198	extensive genetic diversification	166:198	extensive genetic diversification	166:198	Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification.
28734139	0	39	theme	genetic	18:24	arg1	variants					26:33	Ιnfluenza A(H3N2) genetic variants	0:33	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece	0:75	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	6	40	from	clustering	763:772	arg1	subclade					825:832	a newly emerged subclade	809:832	a newly emerged subclade	809:832	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	6	40	from	clustering	763:772	arg1	3C.2a					795:799	the genetic clade 3C.2a	777:799	the genetic clade 3C.2a	777:799	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	7	41	theme	acid	1019:1022	arg1	substitutions					1024:1036	the amino acid substitutions	1009:1036	the amino acid substitutions N122D and T135K in haemagglutinin	1009:1070	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	41	theme	acid	1019:1022	arg1	T135K					1048:1052	T135K	1048:1052	T135K	1048:1052	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	41	theme	acid	1019:1022	arg1	N122D					1038:1042	N122D	1038:1042	N122D	1038:1042	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	11	42	theme	strain	1706:1711	arg1	antigenicity					1677:1688	the antigenicity	1673:1688	the antigenicity of this variant strain and its possible implication in vaccine effectiveness	1673:1765	Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.
28734139	2	43	theme	failure	220:226	arg1	rate					228:231	A high vaccination failure rate	201:231	A high vaccination failure rate	201:231	A high vaccination failure rate was noticed during the 2016/17 season in Greece, especially among the elderly.
28734139	3	44	theme	viruses	405:411	arg1	characteristics					366:380	the genetic characteristics	354:380	the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients	354:455	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	3	45	theme	A	385:385	arg1	viruses					405:411	A(H3N2) circulating viruses	385:411	A(H3N2) circulating viruses	385:411	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	7	46	from	substitutions	1024:1036	arg1	haemagglutinin					1057:1070	haemagglutinin	1057:1070	haemagglutinin	1057:1070	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	0	47	from	patients	49:56	arg1	Greece					70:75	northern Greece	61:75	northern Greece	61:75	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	2	48	theme	vaccination	208:218	arg1	rate					228:231	A high vaccination failure rate	201:231	A high vaccination failure rate	201:231	A high vaccination failure rate was noticed during the 2016/17 season in Greece, especially among the elderly.
28734139	6	49	theme	viruses	751:757	arg1	clustering					763:772	clustering	763:772	clustering	763:772	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	6	49	theme	viruses	751:757	arg1	majority					730:737	The majority	726:737	The majority of analysed viruses	726:757	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	7	50	dep	substitutions	1024:1036	arg1	substitutions					1024:1036	the amino acid substitutions	1009:1036	the amino acid substitutions N122D and T135K in haemagglutinin	1009:1070	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	50	dep	substitutions	1024:1036	arg1	T135K					1048:1052	T135K	1048:1052	T135K	1048:1052	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	7	50	dep	substitutions	1024:1036	arg1	N122D					1038:1042	N122D	1038:1042	N122D	1038:1042	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	3	51	theme	genetic	358:364	arg1	characteristics					366:380	the genetic characteristics	354:380	the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients	354:455	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	4	52	theme	vaccinated	488:497	arg1	patients					516:523	vaccinated and unvaccinated patients	488:523	vaccinated and unvaccinated patients	488:523	Virus samples originated from vaccinated and unvaccinated patients, obtained at the National Influenza Centre for northern Greece.
28734139	6	53	theme	emerged	817:823	arg1	subclade					825:832	a newly emerged subclade	809:832	a newly emerged subclade	809:832	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	2	54	theme	high	203:206	arg1	rate					228:231	A high vaccination failure rate	201:231	A high vaccination failure rate	201:231	A high vaccination failure rate was noticed during the 2016/17 season in Greece, especially among the elderly.
28734139	6	55	theme	analysed	742:749	arg1	viruses					751:757	analysed viruses	742:757	analysed viruses	742:757	The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1.
28734139	9	56	theme	3C.2a1	1345:1350	arg1	subcluster					1352:1361	a specific 3C.2a1 subcluster	1334:1361	a specific 3C.2a1 subcluster	1334:1361	However, viruses belonging to a specific 3C.2a1 subcluster was extensively circulating in northern Greece and among vaccinated individuals.
28734139	5	57	theme	viruses	660:666	arg1	gene					648:651	the haemagglutinin gene	629:651	the haemagglutinin gene of the viruses	629:666	Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed.
28734139	11	58	theme	possible	1721:1728	arg1	implication					1730:1740	its possible implication	1717:1740	its possible implication	1717:1740	Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.
28734139	9	59	theme	vaccinated	1420:1429	arg1	individuals					1431:1441	vaccinated individuals	1420:1441	vaccinated individuals	1420:1441	However, viruses belonging to a specific 3C.2a1 subcluster was extensively circulating in northern Greece and among vaccinated individuals.
28734139	4	60	theme	unvaccinated	503:514	arg1	patients					516:523	vaccinated and unvaccinated patients	488:523	vaccinated and unvaccinated patients	488:523	Virus samples originated from vaccinated and unvaccinated patients, obtained at the National Influenza Centre for northern Greece.
28734139	11	61	theme	implication	1730:1740	arg1	antigenicity					1677:1688	the antigenicity	1673:1688	the antigenicity of this variant strain and its possible implication in vaccine effectiveness	1673:1765	Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.
28734139	10	62	link	N-linked	1539:1546	arg1	sites					1562:1566	N-linked glycosylation sites	1539:1566	N-linked glycosylation sites	1539:1566	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	10	62	link	N-linked	1539:1546	arg1	virus					1575:1579	the virus	1571:1579	the virus	1571:1579	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	7	63	theme	viruses	883:889	arg1	proportion					869:878	The highest proportion	857:878	The highest proportion of viruses detected in vaccinated patients	857:921	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	10	64	theme	antigenic	1502:1510	arg1	sites					1512:1516	antigenic sites	1502:1516	antigenic sites	1502:1516	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	3	65	theme	vaccinated	437:446	arg1	patients					448:455	vaccinated patients	437:455	vaccinated patients	437:455	The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients.
28734139	7	66	theme	highest	861:867	arg1	proportion					869:878	The highest proportion	857:878	The highest proportion of viruses detected in vaccinated patients	857:921	The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin.
28734139	4	67	theme	northern	572:579	arg1	Greece					581:586	northern Greece	572:586	northern Greece	572:586	Virus samples originated from vaccinated and unvaccinated patients, obtained at the National Influenza Centre for northern Greece.
28734139	8	68	theme	3C.2a	1100:1104	arg1	clade					1106:1110	the 3C.2a clade	1096:1110	the 3C.2a clade	1096:1110	Viruses that belong to the 3C.2a clade are generally considered to resemble antigenically to the northern hemisphere vaccine component A/Hong Kong/4801/2014 that was recommended by WHO to be included also into the 2017/18 vaccine.
28734139	1	69	theme	extensive	166:174	arg1	diversification					184:198	extensive genetic diversification	166:198	extensive genetic diversification	166:198	Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification.
28734139	10	70	located	located	1491:1497	arg1	sites					1512:1516	antigenic sites	1502:1516	antigenic sites	1502:1516	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	10	70	located	located	1491:1497	arg2	substitutions					1449:1461	Both substitutions	1444:1461	Both substitutions carried by this strain	1444:1484	Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity.
28734139	2	71	from	season	264:269	arg1	Greece					274:279	Greece	274:279	Greece	274:279	A high vaccination failure rate was noticed during the 2016/17 season in Greece, especially among the elderly.
28734139	0	72	theme	vaccinated	38:47	arg1	patients					49:56	vaccinated patients	38:56	vaccinated patients in northern Greece	38:75	Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.
28734139	11	73	theme	vaccine	1745:1751	arg1	effectiveness					1753:1765	vaccine effectiveness	1745:1765	vaccine effectiveness	1745:1765	Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.
28734139	8	74	theme	2017/18	1287:1293	arg1	vaccine					1295:1301	the 2017/18 vaccine	1283:1301	the 2017/18 vaccine	1283:1301	Viruses that belong to the 3C.2a clade are generally considered to resemble antigenically to the northern hemisphere vaccine component A/Hong Kong/4801/2014 that was recommended by WHO to be included also into the 2017/18 vaccine.
28734139	9	75	theme	specific	1336:1343	arg1	subcluster					1352:1361	a specific 3C.2a1 subcluster	1334:1361	a specific 3C.2a1 subcluster	1334:1361	However, viruses belonging to a specific 3C.2a1 subcluster was extensively circulating in northern Greece and among vaccinated individuals.
28778927	6	0	theme	identified	1068:1077	arg1	sequences					1079:1087	the identified sequences	1064:1087	the identified sequences	1064:1087	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	1	link	N-linked	1135:1142	arg1	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	1	link	N-linked	1135:1142	arg1	sites					1158:1162	N-linked glycosylation sites	1135:1162	N-linked glycosylation sites	1135:1162	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	3	2	theme	new	474:476	arg1	sequences					494:502	257 new putative evasin sequences	470:502	257 new putative evasin sequences	470:502	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	5	3	theme	disulfide	1039:1047	arg1	bonds					1049:1053	these disulfide bonds	1033:1053	these disulfide bonds	1033:1053	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	1	4	theme	host	156:159	arg1	molecules					169:177	host defense molecules	156:177	host defense molecules	156:177	To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules.
28778927	3	5	theme	Ixodidae	654:661	arg1	family					663:668	the Ixodidae family	650:668	the Ixodidae family	650:668	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	6	6	theme	N-linked	1135:1142	arg1	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	6	theme	N-linked	1135:1142	arg1	sites					1158:1162	N-linked glycosylation sites	1135:1162	N-linked glycosylation sites	1135:1162	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	3	7	theme	salivary	530:537	arg1	transcriptomes					551:564	salivary or visceral transcriptomes	530:564	salivary or visceral transcriptomes	530:564	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	7	8	theme	evasin	1243:1248	arg1	proteins					1250:1257	chemokine-binding evasin proteins	1225:1257	chemokine-binding evasin proteins	1225:1257	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	7	9	theme	anti-inflammatory	1421:1437	arg1	proteins					1439:1446	anti-inflammatory proteins	1421:1446	anti-inflammatory proteins	1421:1446	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	7	10	theme	valuable	1404:1411	arg1	pool					1413:1416	a valuable pool	1402:1416	a valuable pool of anti-inflammatory proteins for potential future therapeutic applications	1402:1492	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	5	11	dep	share	927:931	arg1	whereas					995:1001	whereas	995:1001	whereas	995:1001	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	3	12	dep	genomes	519:525	arg1	the					515:517	the	515:517	the	515:517	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	6	13	theme	predicted	1097:1105	arg1	sequences					1124:1132	predicted secretion leader sequences	1097:1132	predicted secretion leader sequences	1097:1132	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	5	14	theme	Cys	958:960	arg1	bonds					987:991	four disulfide bonds	972:991	four disulfide bonds	972:991	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	14	theme	Cys	958:960	arg1	residues					962:969	eight Cys residues	952:969	eight Cys residues (four disulfide bonds)	952:992	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	1	15	theme	defense	161:167	arg1	molecules					169:177	host defense molecules	156:177	host defense molecules	156:177	To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules.
28778927	2	16	gly	glycoproteins	270:282	arg1	glycoproteins					270:282	three salivary glycoproteins	255:282	three salivary glycoproteins named "evasins," which bind to host chemokines	255:329	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	4	17	theme	human	818:822	arg1	chemokines					824:833	human chemokines	818:833	human chemokines	818:833	Nine representative sequences were successfully expressed in Escherichia coli, and eight of the nine candidates exhibited high-affinity binding to human chemokines.
28778927	2	18	theme	salivary	261:268	arg1	glycoproteins					270:282	three salivary glycoproteins	255:282	three salivary glycoproteins named "evasins," which bind to host chemokines	255:329	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	2	19	theme	leukocytes	370:379	arg1	recruitment					355:365	the recruitment	351:365	the recruitment of leukocytes to the location of the tick bite	351:412	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	5	20	theme	disulfide	977:985	arg1	bonds					987:991	four disulfide bonds	972:991	four disulfide bonds	972:991	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	20	theme	disulfide	977:985	arg1	residues					962:969	eight Cys residues	952:969	eight Cys residues (four disulfide bonds)	952:992	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	7	21	theme	proteins	1439:1446	arg1	pool					1413:1416	a valuable pool	1402:1416	a valuable pool of anti-inflammatory proteins for potential future therapeutic applications	1402:1492	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	3	22	theme	visceral	542:549	arg1	transcriptomes					551:564	salivary or visceral transcriptomes	530:564	salivary or visceral transcriptomes	530:564	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	6	23	gly	glycosylation	1144:1156	arg2	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	23	gly	glycosylation	1144:1156	arg2	sites					1158:1162	N-linked glycosylation sites	1135:1162	N-linked glycosylation sites	1135:1162	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	23	gly	glycosylation	1144:1156	arg1	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	2	24	theme	bite	409:412	arg1	location					388:395	the location	384:395	the location of the tick bite	384:412	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	4	25	theme	candidates	772:781	arg1	candidates					772:781	the nine candidates	763:781	the nine candidates	763:781	Nine representative sequences were successfully expressed in Escherichia coli, and eight of the nine candidates exhibited high-affinity binding to human chemokines.
28778927	4	25	theme	candidates	772:781	arg1	eight					754:758	eight	754:758	eight	754:758	Nine representative sequences were successfully expressed in Escherichia coli, and eight of the nine candidates exhibited high-affinity binding to human chemokines.
28778927	5	26	theme	C6	1003:1004	arg1	evasins					1006:1012	C6 evasins	1003:1012	C6 evasins	1003:1012	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	27	theme	conserved	935:943	arg1	set					945:947	a conserved set	933:947	a conserved set of eight Cys residues (four disulfide bonds)	933:992	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	27	theme	conserved	935:943	arg1	bonds					987:991	four disulfide bonds	972:991	four disulfide bonds	972:991	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	27	theme	conserved	935:943	arg1	residues					962:969	eight Cys residues	952:969	eight Cys residues (four disulfide bonds)	952:992	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	4	28	theme	high-affinity	793:805	arg1	binding					807:813	high-affinity binding	793:813	high-affinity binding to human chemokines	793:833	Nine representative sequences were successfully expressed in Escherichia coli, and eight of the nine candidates exhibited high-affinity binding to human chemokines.
28778927	7	29	theme	tick	1286:1289	arg1	species					1291:1297	tick species	1286:1297	tick species of the Ixodidae family	1286:1320	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	2	30	theme	tick	404:407	arg1	bite					409:412	the tick bite	400:412	the tick bite	400:412	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	5	31	dep	subfamilies	903:913	arg1	share					927:931	share	927:931	share a conserved set of eight Cys residues (four disulfide bonds)	927:992	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	2	32	theme	evasins	291:297	arg1	"					299:299	evasins,"	291:299	"	299:299	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	0	33	theme	chemokine-inhibitory	33:52	arg1	Ticks					0:4	Ticks	0:4	Ticks from diverse genera	0:24	Ticks from diverse genera encode chemokine-inhibitory evasin proteins.
28778927	0	33	theme	chemokine-inhibitory	33:52	arg1	proteins					61:68	chemokine-inhibitory evasin proteins	33:68	chemokine-inhibitory evasin proteins	33:68	Ticks from diverse genera encode chemokine-inhibitory evasin proteins.
28778927	7	34	dep	potential	1452:1460	arg1	therapeutic					1469:1479	therapeutic	1469:1479	therapeutic	1469:1479	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	3	35	theme	numerous	569:576	arg1	ticks					583:587	numerous hard ticks	569:587	numerous hard ticks	569:587	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	3	36	theme	sequence	421:428	arg1	searches					441:448	sequence similarity searches	421:448	sequence similarity searches	421:448	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	7	37	theme	Ixodidae	1306:1313	arg1	family					1315:1320	the Ixodidae family	1302:1320	the Ixodidae family	1302:1320	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	3	38	theme	genera	603:608	arg1	Rhipicephalus					610:622	the genera Rhipicephalus	599:622	the genera Rhipicephalus	599:622	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	3	39	theme	hard	578:581	arg1	ticks					583:587	numerous hard ticks	569:587	numerous hard ticks	569:587	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	7	40	theme	important	1342:1350	arg1	roles					1352:1356	important roles	1342:1356	important roles	1342:1356	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	3	41	theme	similarity	430:439	arg1	searches					441:448	sequence similarity searches	421:448	sequence similarity searches	421:448	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	5	42	contain	have	1014:1017	arg2	bonds					1049:1053	these disulfide bonds	1033:1053	these disulfide bonds	1033:1053	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	42	contain	have	1014:1017	arg1	evasins					1006:1012	C6 evasins	1003:1012	C6 evasins	1003:1012	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	42	contain	have	1014:1017	arg2	three					1024:1028	three	1024:1028	three	1024:1028	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	43	theme	bonds	1049:1053	arg1	three					1024:1028	three	1024:1028	three	1024:1028	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	43	theme	bonds	1049:1053	arg1	bonds					1049:1053	these disulfide bonds	1033:1053	these disulfide bonds	1033:1053	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	6	44	theme	tyrosine	1188:1195	arg1	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	4	45	theme	representative	676:689	arg1	sequences					691:699	Nine representative sequences	671:699	Nine representative sequences	671:699	Nine representative sequences were successfully expressed in Escherichia coli, and eight of the nine candidates exhibited high-affinity binding to human chemokines.
28778927	0	46	theme	evasin	54:59	arg1	Ticks					0:4	Ticks	0:4	Ticks from diverse genera	0:24	Ticks from diverse genera encode chemokine-inhibitory evasin proteins.
28778927	0	46	theme	evasin	54:59	arg1	proteins					61:68	chemokine-inhibitory evasin proteins	33:68	chemokine-inhibitory evasin proteins	33:68	Ticks from diverse genera encode chemokine-inhibitory evasin proteins.
28778927	3	47	theme	family	663:668	arg1	Amblyomma					625:633	Amblyomma	625:633	Amblyomma	625:633	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	3	47	theme	family	663:668	arg1	Ixodes					640:645	Ixodes	640:645	Ixodes	640:645	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	3	47	theme	family	663:668	arg1	Rhipicephalus					610:622	the genera Rhipicephalus	599:622	the genera Rhipicephalus	599:622	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	2	48	theme	tick	199:202	arg1	sanguineus					218:227	the tick Rhipicephalus sanguineus	195:227	the tick Rhipicephalus sanguineus	195:227	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	2	49	theme	Rhipicephalus	204:216	arg1	sanguineus					218:227	the tick Rhipicephalus sanguineus	195:227	the tick Rhipicephalus sanguineus	195:227	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	3	50	theme	putative	478:485	arg1	sequences					494:502	257 new putative evasin sequences	470:502	257 new putative evasin sequences	470:502	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	2	51	theme	host	315:318	arg1	chemokines					320:329	host chemokines	315:329	host chemokines	315:329	In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named "evasins," which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite.
28778927	7	52	theme	potential	1452:1460	arg1	applications					1481:1492	potential future therapeutic applications	1452:1492	potential future therapeutic applications	1452:1492	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	7	53	theme	chemokine-binding	1225:1241	arg1	proteins					1250:1257	chemokine-binding evasin proteins	1225:1257	chemokine-binding evasin proteins	1225:1257	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	6	54	theme	sulfation	1197:1205	arg1	sequences					1124:1132	predicted secretion leader sequences	1097:1132	predicted secretion leader sequences	1097:1132	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	54	theme	sulfation	1197:1205	arg1	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	54	theme	sulfation	1197:1205	arg1	site					1180:1183	a putative site	1169:1183	a putative site of tyrosine sulfation	1169:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	54	theme	sulfation	1197:1205	arg1	sites					1158:1162	N-linked glycosylation sites	1135:1162	N-linked glycosylation sites	1135:1162	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	1	55	theme	many	122:125	arg1	factors					136:142	many salivary factors	122:142	many salivary factors that target host defense molecules	122:177	To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules.
28778927	6	56	theme	leader	1117:1122	arg1	sequences					1124:1132	predicted secretion leader sequences	1097:1132	predicted secretion leader sequences	1097:1132	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	57	theme	secretion	1107:1115	arg1	sequences					1124:1132	predicted secretion leader sequences	1097:1132	predicted secretion leader sequences	1097:1132	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	5	58	theme	residues	962:969	arg1	set					945:947	a conserved set	933:947	a conserved set of eight Cys residues (four disulfide bonds)	933:992	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	58	theme	residues	962:969	arg1	bonds					987:991	four disulfide bonds	972:991	four disulfide bonds	972:991	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	5	58	theme	residues	962:969	arg1	residues					962:969	eight Cys residues	952:969	eight Cys residues (four disulfide bonds)	952:992	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	6	59	theme	putative	1171:1178	arg1	site					1180:1183	a putative site	1169:1183	a putative site of tyrosine sulfation	1169:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	59	theme	putative	1171:1178	arg1	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	1	60	theme	salivary	127:134	arg1	factors					136:142	many salivary factors	122:142	many salivary factors that target host defense molecules	122:177	To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules.
28778927	7	61	theme	family	1315:1320	arg1	species					1291:1297	tick species	1286:1297	tick species of the Ixodidae family	1286:1320	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28778927	5	62	theme	C8	916:917	arg1	evasins					919:925	C8 evasins	916:925	C8 evasins	916:925	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	6	63	contain	contain	1089:1095	arg1	sequences					1079:1087	the identified sequences	1064:1087	the identified sequences	1064:1087	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	63	contain	contain	1089:1095	arg2	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	63	contain	contain	1089:1095	arg1	Most					1056:1059	Most	1056:1059	Most	1056:1059	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	63	contain	contain	1089:1095	arg2	sequences					1124:1132	predicted secretion leader sequences	1097:1132	predicted secretion leader sequences	1097:1132	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	63	contain	contain	1089:1095	arg2	site					1180:1183	a putative site	1169:1183	a putative site of tyrosine sulfation	1169:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	63	contain	contain	1089:1095	arg2	sites					1158:1162	N-linked glycosylation sites	1135:1162	N-linked glycosylation sites	1135:1162	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	5	64	theme	Sequence	836:843	arg1	alignments					845:854	Sequence alignments	836:854	Sequence alignments	836:854	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	3	65	theme	ticks	583:587	arg1	transcriptomes					551:564	salivary or visceral transcriptomes	530:564	salivary or visceral transcriptomes	530:564	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	3	65	theme	ticks	583:587	arg1	genomes					519:525	genomes	519:525	genomes	519:525	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	3	66	theme	evasin	487:492	arg1	sequences					494:502	257 new putative evasin sequences	470:502	257 new putative evasin sequences	470:502	Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family.
28778927	6	67	theme	glycosylation	1144:1156	arg1	sulfation					1197:1205	tyrosine sulfation	1188:1205	tyrosine sulfation	1188:1205	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	6	67	theme	glycosylation	1144:1156	arg1	sites					1158:1162	N-linked glycosylation sites	1135:1162	N-linked glycosylation sites	1135:1162	Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation.
28778927	0	68	from	genera	19:24	arg1	Ticks					0:4	Ticks	0:4	Ticks from diverse genera	0:24	Ticks from diverse genera encode chemokine-inhibitory evasin proteins.
28778927	0	68	from	genera	19:24	arg1	proteins					61:68	chemokine-inhibitory evasin proteins	33:68	chemokine-inhibitory evasin proteins	33:68	Ticks from diverse genera encode chemokine-inhibitory evasin proteins.
28778927	0	69	theme	diverse	11:17	arg1	genera					19:24	diverse genera	11:24	diverse genera	11:24	Ticks from diverse genera encode chemokine-inhibitory evasin proteins.
28778927	5	70	theme	evasins	886:892	arg1	classification					864:877	classification	864:877	classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds	864:1053	Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds.
28778927	7	71	theme	host	1372:1375	arg1	defenses					1377:1384	host defenses	1372:1384	host defenses	1372:1384	We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.
28366604	0	0	theme	vaccine-elicited	85:100	arg1	neutralizing					107:118	vaccine-elicited CD4i neutralizing and anti-V2 antibody responses	85:149	neutralizing	107:118	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	0	1	from	substitution	13:24	arg1	C2					29:30	C2	29:30	C2	29:30	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	5	2	theme	yeast	982:986	arg1	mapping					1004:1010	yeast antigen display mapping	982:1010	yeast antigen display mapping	982:1010	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	6	3	theme	elevated	1098:1105	arg1	activity					1155:1162	elevated antibody-dependent cellular cytotoxicity (ADCC) activity	1098:1162	elevated antibody-dependent cellular cytotoxicity (ADCC) activity	1098:1162	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	8	4	theme	domain	1308:1313	arg1	determinant					1284:1294	a determinant	1282:1294	a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239	1282:1391	Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239.
28366604	2	5	theme	CD4i	371:374	arg1	Abs					389:391	Abs	389:391	Abs	389:391	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	2	5	theme	CD4i	371:374	arg1	antibodies					377:386	CD4-induced (CD4i) antibodies	358:386	CD4-induced (CD4i) antibodies (Abs)	358:392	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	5	6	theme	anti-V2	934:940	arg1	responses					945:953	anti-V2 Ab responses	934:953	anti-V2 Ab responses	934:953	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	4	7	theme	CD4i	781:784	arg1	domain					789:794	the CD4i Ab domain	777:794	the CD4i Ab domain	777:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	8	8	theme	anti-V2	1350:1356	arg1	Ab					1358:1359	vaccine-elicited anti-V2 Ab and ADCC responses	1333:1378	Ab	1358:1359	Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239.
28366604	9	9	theme	immunogens	1443:1452	arg1	design					1433:1438	design	1433:1438	design of immunogens to direct B cell recognition	1433:1481	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	5	10	theme	domain	887:892	arg1	immunogenicity					862:875	the immunogenicity	858:875	the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses	858:953	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	5	11	theme	antigen	988:994	arg1	mapping					1004:1010	yeast antigen display mapping	982:1010	yeast antigen display mapping	982:1010	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	0	12	theme	CD4i	102:105	arg1	neutralizing					107:118	vaccine-elicited CD4i neutralizing and anti-V2 antibody responses	85:149	neutralizing	107:118	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	9	13	theme	B	1464:1464	arg1	recognition					1471:1481	direct B cell recognition	1457:1481	direct B cell recognition	1457:1481	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	8	14	theme	vaccine-elicited	1333:1348	arg1	Ab					1358:1359	vaccine-elicited anti-V2 Ab and ADCC responses	1333:1378	Ab	1358:1359	Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239.
28366604	2	15	theme	HIV/SIV	302:308	arg1	infections					310:319	HIV/SIV infections	302:319	HIV/SIV infections	302:319	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	3	16	from	levels	604:609	arg1	animals					639:645	experimental animals	626:645	experimental animals	626:645	Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals.
28366604	6	17	theme	cytotoxicity	1135:1146	arg1	activity					1155:1162	elevated antibody-dependent cellular cytotoxicity (ADCC) activity	1098:1162	elevated antibody-dependent cellular cytotoxicity (ADCC) activity	1098:1162	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	0	18	theme	anti-V2	124:130	arg1	responses					141:149	vaccine-elicited CD4i neutralizing and anti-V2 antibody responses	85:149	responses	141:149	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	9	19	theme	cell	1466:1469	arg1	recognition					1471:1481	direct B cell recognition	1457:1481	direct B cell recognition	1457:1481	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	7	20	theme	Ab	1218:1219	arg1	titer					1221:1225	the anti-V2 Ab titer	1206:1225	the anti-V2 Ab titer	1206:1225	ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer.
28366604	5	21	theme	higher	903:908	arg1	titers					910:915	higher titers	903:915	higher titers	903:915	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	9	22	theme	Ab-based	1508:1515	arg1	vaccine					1521:1527	an Ab-based HIV vaccine	1505:1527	an Ab-based HIV vaccine	1505:1527	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	0	23	theme	Single	0:5	arg1	substitution					13:24	Single N277A substitution	0:24	Single N277A substitution in C2 of simian immunodeficiency virus envelope	0:72	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	6	24	theme	N277A-mutated	1068:1080	arg1	gp160					1082:1086	the N277A-mutated gp160	1064:1086	the N277A-mutated gp160	1064:1086	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	0	25	theme	N277A	7:11	arg1	substitution					13:24	Single N277A substitution	0:24	Single N277A substitution in C2 of simian immunodeficiency virus envelope	0:72	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	9	26	theme	vaccine	1521:1527	arg1	development					1490:1500	the development	1486:1500	the development of an Ab-based HIV vaccine	1486:1527	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	2	27	theme	abundant	335:342	arg1	production					344:353	the abundant production	331:353	the abundant production of CD4-induced (CD4i) antibodies (Abs)	331:392	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	2	28	theme	steric	431:436	arg1	restrictions					438:449	steric restrictions	431:449	steric restrictions following gp120 binding to CD4 on target cells	431:496	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	7	29	theme	Ab	1252:1253	arg1	titer					1255:1259	CD4i Ab titer	1247:1259	CD4i Ab titer	1247:1259	ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer.
28366604	3	30	theme	SIVmac239	566:574	arg1	gp160					576:580	SIVmac239 gp160	566:580	SIVmac239 gp160	566:580	Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals.
28366604	9	31	theme	HIV	1517:1519	arg1	vaccine					1521:1527	an Ab-based HIV vaccine	1505:1527	an Ab-based HIV vaccine	1505:1527	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	8	32	theme	CD4i	1303:1306	arg1	domain					1308:1313	the CD4i domain	1299:1313	the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239	1299:1391	Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239.
28366604	9	33	contain	have	1411:1414	arg1	findings					1398:1405	Our findings	1394:1405	Our findings	1394:1405	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	9	33	contain	have	1411:1414	arg2	implications					1416:1427	implications	1416:1427	implications for design of immunogens to direct B cell recognition	1416:1481	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	3	34	theme	vaccinia-based	533:546	arg1	vaccines					548:555	vaccinia-based vaccines	533:555	vaccinia-based vaccines encoding SIVmac239 gp160	533:580	Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals.
28366604	1	35	theme	capable	209:215	arg1	immunogens					198:207	immunogens	198:207	immunogens capable of eliciting protective host humoral immunity	198:261	An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified.
28366604	5	36	theme	Ab	942:943	arg1	responses					945:953	anti-V2 Ab responses	934:953	anti-V2 Ab responses	934:953	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	0	37	theme	antibody	132:139	arg1	responses					141:149	vaccine-elicited CD4i neutralizing and anti-V2 antibody responses	85:149	responses	141:149	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	5	38	theme	responses	945:953	arg1	frequency					921:929	frequency	921:929	frequency of anti-V2 Ab responses	921:953	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	5	38	theme	responses	945:953	arg1	titers					910:915	higher titers	903:915	higher titers	903:915	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	4	39	theme	glycosylation	690:702	arg1	site					704:707	a highly conserved N-linked glycosylation site N277	662:712	a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain	662:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	4	40	theme	N-linked	681:688	arg1	site					704:707	a highly conserved N-linked glycosylation site N277	662:712	a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain	662:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	7	41	theme	ADCC	1165:1168	arg1	activity					1170:1177	ADCC activity	1165:1177	ADCC activity	1165:1177	ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer.
28366604	2	42	from	CD4	478:480	arg1	cells					492:496	target cells	485:496	target cells	485:496	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	9	43	theme	direct	1457:1462	arg1	recognition					1471:1481	direct B cell recognition	1457:1481	direct B cell recognition	1457:1481	Our findings may have implications for design of immunogens to direct B cell recognition in the development of an Ab-based HIV vaccine.
28366604	6	44	theme	immune	1040:1045	arg1	sera					1047:1050	immune sera	1040:1050	immune sera elicited by the N277A-mutated gp160	1040:1086	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	3	45	theme	high	599:602	arg1	levels					604:609	high levels	599:609	high levels of CD4i Abs in experimental animals	599:645	Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals.
28366604	1	46	theme	protective	230:239	arg1	immunity					254:261	protective host humoral immunity	230:261	protective host humoral immunity	230:261	An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified.
28366604	0	47	theme	immunodeficiency	42:57	arg1	virus					59:63	simian immunodeficiency virus	35:63	simian immunodeficiency virus envelope	35:72	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	5	48	theme	V2	884:885	arg1	domain					887:892	the V2 domain	880:892	the V2 domain yielding higher titers and frequency of anti-V2 Ab responses	880:953	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	5	49	theme	single	809:814	arg1	substitution					822:833	a single N277A substitution	807:833	a single N277A substitution	807:833	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	0	50	theme	virus	59:63	arg1	envelope					65:72	simian immunodeficiency virus envelope	35:72	simian immunodeficiency virus envelope	35:72	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	6	51	theme	cellular	1126:1133	arg1	ADCC					1149:1152	ADCC	1149:1152	ADCC	1149:1152	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	6	51	theme	cellular	1126:1133	arg1	cytotoxicity					1135:1146	antibody-dependent cellular cytotoxicity	1107:1146	elevated antibody-dependent cellular cytotoxicity (ADCC) activity	1098:1162	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	0	52	theme	simian	35:40	arg1	virus					59:63	simian immunodeficiency virus	35:63	simian immunodeficiency virus envelope	35:72	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	3	53	theme	experimental	626:637	arg1	animals					639:645	experimental animals	626:645	experimental animals	626:645	Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals.
28366604	2	54	theme	CD4-induced	358:368	arg1	Abs					389:391	Abs	389:391	Abs	389:391	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	2	54	theme	CD4-induced	358:368	arg1	antibodies					377:386	CD4-induced (CD4i) antibodies	358:386	CD4-induced (CD4i) antibodies (Abs)	358:392	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	4	55	gly	glycosylation	690:702	arg2	site					704:707	a highly conserved N-linked glycosylation site N277	662:712	a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain	662:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	4	55	gly	glycosylation	690:702	arg2	N277					709:712	N277	709:712	N277	709:712	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	4	56	theme	Ab	786:787	arg1	domain					789:794	the CD4i Ab domain	777:794	the CD4i Ab domain	777:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	3	57	theme	CD4i	614:617	arg1	Abs					619:621	CD4i Abs	614:621	CD4i Abs	614:621	Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals.
28366604	4	58	theme	conserved	671:679	arg1	site					704:707	a highly conserved N-linked glycosylation site N277	662:712	a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain	662:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	4	59	theme	C2	721:722	arg1	region					724:729	the C2 region	717:729	the C2 region which strongly affected the immunogenicity of the CD4i Ab domain	717:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	4	60	link	N-linked	681:688	arg1	site					704:707	a highly conserved N-linked glycosylation site N277	662:712	a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain	662:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	1	61	theme	host	241:244	arg1	immunity					254:261	protective host humoral immunity	230:261	protective host humoral immunity	230:261	An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified.
28366604	3	62	theme	Abs	619:621	arg1	levels					604:609	high levels	599:609	high levels of CD4i Abs in experimental animals	599:645	Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals.
28366604	1	63	theme	HIV	165:167	arg1	vaccine					169:175	An effective HIV vaccine	152:175	An effective HIV vaccine	152:175	An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified.
28366604	8	64	theme	ADCC	1365:1368	arg1	responses					1370:1378	vaccine-elicited anti-V2 Ab and ADCC responses	1333:1378	responses	1370:1378	Thus, we identified a determinant of the CD4i domain that might affect vaccine-elicited anti-V2 Ab and ADCC responses to SIVmac239.
28366604	1	65	theme	humoral	246:252	arg1	immunity					254:261	protective host humoral immunity	230:261	protective host humoral immunity	230:261	An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified.
28366604	0	66	theme	envelope	65:72	arg1	substitution					13:24	Single N277A substitution	0:24	Single N277A substitution in C2 of simian immunodeficiency virus envelope	0:72	Single N277A substitution in C2 of simian immunodeficiency virus envelope influences vaccine-elicited CD4i neutralizing and anti-V2 antibody responses.
28366604	6	67	theme	antibody-dependent	1107:1124	arg1	ADCC					1149:1152	ADCC	1149:1152	ADCC	1149:1152	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	6	67	theme	antibody-dependent	1107:1124	arg1	cytotoxicity					1135:1146	antibody-dependent cellular cytotoxicity	1107:1146	elevated antibody-dependent cellular cytotoxicity (ADCC) activity	1098:1162	Importantly, immune sera elicited by the N277A-mutated gp160 exhibited elevated antibody-dependent cellular cytotoxicity (ADCC) activity.
28366604	5	68	theme	display	996:1002	arg1	mapping					1004:1010	yeast antigen display mapping	982:1010	yeast antigen display mapping	982:1010	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	5	69	theme	N277A	816:820	arg1	substitution					822:833	a single N277A substitution	807:833	a single N277A substitution	807:833	Moreover, a single N277A substitution significantly enhanced the immunogenicity of the V2 domain yielding higher titers and frequency of anti-V2 Ab responses as determined by ELISA and yeast antigen display mapping, respectively.
28366604	1	70	theme	effective	155:163	arg1	vaccine					169:175	An effective HIV vaccine	152:175	An effective HIV vaccine	152:175	An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified.
28366604	7	71	theme	CD4i	1247:1250	arg1	titer					1255:1259	CD4i Ab titer	1247:1259	CD4i Ab titer	1247:1259	ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer.
28366604	2	72	theme	target	485:490	arg1	cells					492:496	target cells	485:496	target cells	485:496	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	7	73	theme	anti-V2	1210:1216	arg1	titer					1221:1225	the anti-V2 Ab titer	1206:1225	the anti-V2 Ab titer	1206:1225	ADCC activity correlated positively with the anti-V2 Ab titer yet, inversely with CD4i Ab titer.
28366604	4	74	theme	domain	789:794	arg1	immunogenicity					759:772	the immunogenicity	755:772	the immunogenicity of the CD4i Ab domain	755:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
28366604	2	75	theme	antibodies	377:386	arg1	production					344:353	the abundant production	331:353	the abundant production of CD4-induced (CD4i) antibodies (Abs)	331:392	Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells.
28366604	4	76	from	site	704:707	arg1	region					724:729	the C2 region	717:729	the C2 region which strongly affected the immunogenicity of the CD4i Ab domain	717:794	We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain.
30040982	0	0	from	regulation	20:29	arg1	cells					79:83	breast cancer cells	65:83	breast cancer cells	65:83	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	8	1	theme	ST3GAL1	1039:1045	arg1	expression					1025:1034	high expression	1020:1034	high expression of ST3GAL1	1020:1045	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	8	2	theme	clinical	1072:1079	arg1	outcome					1081:1087	poor clinical outcome	1067:1087	poor clinical outcome in patients with late stage breast cancer	1067:1129	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	5	3	theme	cell	734:737	arg1	proliferation					739:751	GDNF-mediated cell proliferation	720:751	GDNF-mediated cell proliferation	720:751	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	0	4	theme	cancer	72:77	arg1	cells					79:83	breast cancer cells	65:83	breast cancer cells	65:83	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	3	5	from	site	416:419	arg1	RET					433:435	RET	433:435	RET	433:435	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	3	5	from	site	416:419	arg1	GFRA1					424:428	GFRA1	424:428	GFRA1	424:428	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	5	6	theme	breast	631:636	arg1	cells					645:649	breast cancer cells	631:649	breast cancer cells	631:649	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	7	7	theme	inhibitors	981:990	arg1	efficacy					969:976	anti-cancer efficacy	957:976	anti-cancer efficacy of inhibitors of RET and/or ER	957:1007	Finally, we demonstrated ST3GAL1 knockdown augments anti-cancer efficacy of inhibitors of RET and/or ER.
30040982	3	8	gly	sialylation	404:414	arg2	site					416:419	no O-linked sialylation site	392:419	no O-linked sialylation site on GFRA1 or RET	392:435	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	8	9	theme	grade	1223:1227	arg1	tumors					1229:1234	high grade tumors	1218:1234	high grade tumors	1218:1234	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	4	10	theme	breast	589:594	arg1	cells					603:607	ER-positive breast cancer cells	577:607	ER-positive breast cancer cells	577:607	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	8	11	theme	ST3GAL1	1159:1165	arg1	expression					1140:1149	high expression	1135:1149	high expression of both ST3GAL1 and GFRA1	1135:1175	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	2	12	theme	transcriptional	272:286	arg1	activation					288:297	estrogen-independent transcriptional activation	251:297	estrogen-independent transcriptional activation	251:297	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	4	13	theme	ER-positive	577:587	arg1	cells					603:607	ER-positive breast cancer cells	577:607	ER-positive breast cancer cells	577:607	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	5	14	theme	GDNF-mediated	720:732	arg1	proliferation					739:751	GDNF-mediated cell proliferation	720:751	GDNF-mediated cell proliferation	720:751	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	8	15	theme	poor	1067:1070	arg1	outcome					1081:1087	poor clinical outcome	1067:1087	poor clinical outcome in patients with late stage breast cancer	1067:1129	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	5	16	theme	Silencing	610:618	arg1	ST3GAL1					620:626	Silencing ST3GAL1	610:626	Silencing ST3GAL1 in breast cancer cells	610:649	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	2	17	theme	estrogen-independent	251:270	arg1	activation					288:297	estrogen-independent transcriptional activation	251:297	estrogen-independent transcriptional activation	251:297	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	1	18	theme	-positive	143:151	arg1	cancers					160:166	estrogen receptor (ER)-positive breast cancers	121:166	estrogen receptor (ER)-positive breast cancers	121:166	GFRA1 and RET are overexpressed in estrogen receptor (ER)-positive breast cancers.
30040982	3	19	theme	membrane	345:352	arg1	RET					337:339	RET	337:339	RET	337:339	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	3	19	theme	membrane	345:352	arg1	proteins					354:361	membrane proteins	345:361	membrane proteins which are N-glycosylated	345:386	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	3	19	theme	membrane	345:352	arg1	GFRA1					327:331	GFRA1	327:331	GFRA1	327:331	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	6	20	theme	breast	889:894	arg1	cancers					896:902	breast cancers	889:902	breast cancers	889:902	Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers.
30040982	1	21	theme	breast	153:158	arg1	cancers					160:166	estrogen receptor (ER)-positive breast cancers	121:166	estrogen receptor (ER)-positive breast cancers	121:166	GFRA1 and RET are overexpressed in estrogen receptor (ER)-positive breast cancers.
30040982	0	22	theme	feedback	11:18	arg1	regulation					20:29	Reciprocal feedback regulation	0:29	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.	0:84	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	4	23	link	O-linked	509:516	arg1	sialylation					518:528	ST3GAL1-mediated O-linked sialylation	492:528	ST3GAL1-mediated O-linked sialylation	492:528	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	3	24	gly	N-glycosylated	373:386	arg1	reported					446:453	reported	446:453	has been reported	437:453	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	3	24	gly	N-glycosylated	373:386	arg1	RET					337:339	RET	337:339	RET	337:339	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	3	24	gly	N-glycosylated	373:386	arg1	proteins					354:361	membrane proteins	345:361	membrane proteins which are N-glycosylated	345:386	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	3	24	gly	N-glycosylated	373:386	arg1	GFRA1					327:331	GFRA1	327:331	GFRA1	327:331	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	7	25	theme	anti-cancer	957:967	arg1	efficacy					969:976	anti-cancer efficacy	957:976	anti-cancer efficacy of inhibitors of RET and/or ER	957:1007	Finally, we demonstrated ST3GAL1 knockdown augments anti-cancer efficacy of inhibitors of RET and/or ER.
30040982	3	26	theme	sialylation	404:414	arg1	site					416:419	no O-linked sialylation site	392:419	no O-linked sialylation site on GFRA1 or RET	392:435	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	8	27	theme	stage	1111:1115	arg1	cancer					1124:1129	late stage breast cancer	1106:1129	late stage breast cancer	1106:1129	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	0	28	theme	Reciprocal	0:9	arg1	regulation					20:29	Reciprocal feedback regulation	0:29	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.	0:84	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	5	29	theme	cancer	638:643	arg1	cells					645:649	breast cancer cells	631:649	breast cancer cells	631:649	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	7	30	theme	ST3GAL1	930:936	arg1	knockdown					938:946	ST3GAL1 knockdown	930:946	ST3GAL1 knockdown	930:946	Finally, we demonstrated ST3GAL1 knockdown augments anti-cancer efficacy of inhibitors of RET and/or ER.
30040982	2	31	theme	genes	315:319	arg1	activation					288:297	estrogen-independent transcriptional activation	251:297	estrogen-independent transcriptional activation	251:297	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	2	31	theme	genes	315:319	arg1	phosphorylation					231:245	ER phosphorylation	228:245	ER phosphorylation	228:245	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	6	32	from	signaling	876:884	arg1	cancers					896:902	breast cancers	889:902	breast cancers	889:902	Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers.
30040982	8	33	theme	GFRA1	1171:1175	arg1	expression					1140:1149	high expression	1135:1149	high expression of both ST3GAL1 and GFRA1	1135:1175	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	6	34	theme	ST3GAL1	794:800	arg1	transcription					777:789	transcription	777:789	transcription of ST3GAL1	777:800	Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers.
30040982	2	35	theme	ER-dependent	302:313	arg1	genes					315:319	ER-dependent genes	302:319	ER-dependent genes	302:319	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	4	36	theme	GDNF-induced	551:562	arg1	signaling					564:572	GDNF-induced signaling	551:572	GDNF-induced signaling in ER-positive breast cancer cells	551:607	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	5	37	theme	ERα	704:706	arg1	proliferation					739:751	GDNF-mediated cell proliferation	720:751	GDNF-mediated cell proliferation	720:751	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	5	37	theme	ERα	704:706	arg1	phosphorylation					672:686	GDNF-induced phosphorylation	659:686	GDNF-induced phosphorylation of RET, AKT and ERα	659:706	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	8	38	theme	high	1218:1221	arg1	tumors					1229:1234	high grade tumors	1218:1234	high grade tumors	1218:1234	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	8	39	theme	late	1106:1109	arg1	cancer					1124:1129	late stage breast cancer	1106:1129	late stage breast cancer	1106:1129	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	6	40	theme	GDNF/GFRA1/RET	861:874	arg1	signaling					876:884	ST3GAL1 and GDNF/GFRA1/RET signaling	849:884	ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers	849:902	Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers.
30040982	3	41	link	O-linked	395:402	arg1	site					416:419	no O-linked sialylation site	392:419	no O-linked sialylation site on GFRA1 or RET	392:435	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	5	42	from	ST3GAL1	620:626	arg1	cells					645:649	breast cancer cells	631:649	breast cancer cells	631:649	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	0	43	theme	ST3GAL1	34:40	arg1	regulation					20:29	Reciprocal feedback regulation	0:29	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.	0:84	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	4	44	theme	sialylation	518:528	arg1	substrate					479:487	a substrate	477:487	a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells	477:607	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	2	45	theme	RET	203:205	arg1	signaling					207:215	RET signaling	203:215	RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes	203:319	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	4	46	theme	ST3GAL1-mediated	492:507	arg1	sialylation					518:528	ST3GAL1-mediated O-linked sialylation	492:528	ST3GAL1-mediated O-linked sialylation	492:528	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	4	47	from	signaling	564:572	arg1	cells					603:607	ER-positive breast cancer cells	577:607	ER-positive breast cancer cells	577:607	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	3	48	theme	O-linked	395:402	arg1	site					416:419	no O-linked sialylation site	392:419	no O-linked sialylation site on GFRA1 or RET	392:435	Both GFRA1 and RET are membrane proteins which are N-glycosylated but no O-linked sialylation site on GFRA1 or RET has been reported.
30040982	4	49	theme	O-linked	509:516	arg1	sialylation					518:528	ST3GAL1-mediated O-linked sialylation	492:528	ST3GAL1-mediated O-linked sialylation	492:528	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	8	50	theme	breast	1117:1122	arg1	cancer					1124:1129	late stage breast cancer	1106:1129	late stage breast cancer	1106:1129	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	6	51	theme	ST3GAL1	849:855	arg1	signaling					876:884	ST3GAL1 and GDNF/GFRA1/RET signaling	849:884	ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers	849:902	Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers.
30040982	1	52	dep	-positive	143:151	arg1	receptor					130:137	estrogen receptor	121:137	estrogen receptor	121:137	GFRA1 and RET are overexpressed in estrogen receptor (ER)-positive breast cancers.
30040982	0	53	theme	GFRA1	46:50	arg1	regulation					20:29	Reciprocal feedback regulation	0:29	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.	0:84	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	5	54	theme	RET	691:693	arg1	proliferation					739:751	GDNF-mediated cell proliferation	720:751	GDNF-mediated cell proliferation	720:751	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	5	54	theme	RET	691:693	arg1	phosphorylation					672:686	GDNF-induced phosphorylation	659:686	GDNF-induced phosphorylation of RET, AKT and ERα	659:706	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	0	55	dep	ST3GAL1	34:40	arg1	signaling					52:60	signaling	52:60	signaling	52:60	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	5	56	theme	GDNF-induced	659:670	arg1	phosphorylation					672:686	GDNF-induced phosphorylation	659:686	GDNF-induced phosphorylation of RET, AKT and ERα	659:706	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	8	57	theme	high	1020:1023	arg1	expression					1025:1034	high expression	1020:1034	high expression of ST3GAL1	1020:1045	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	8	58	from	outcome	1081:1087	arg1	patients					1092:1099	patients	1092:1099	patients with late stage breast cancer	1092:1129	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	2	59	theme	GDNF	180:183	arg1	Binding					169:175	Binding	169:175	Binding of GDNF to GFRA1	169:192	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	5	60	theme	AKT	696:698	arg1	proliferation					739:751	GDNF-mediated cell proliferation	720:751	GDNF-mediated cell proliferation	720:751	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	5	60	theme	AKT	696:698	arg1	phosphorylation					672:686	GDNF-induced phosphorylation	659:686	GDNF-induced phosphorylation of RET, AKT and ERα	659:706	Silencing ST3GAL1 in breast cancer cells reduced GDNF-induced phosphorylation of RET, AKT and ERα, as well as GDNF-mediated cell proliferation.
30040982	6	61	theme	feedback	824:831	arg1	loop					833:836	a positive feedback loop	813:836	a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers	813:902	Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers.
30040982	2	62	theme	ER	228:229	arg1	phosphorylation					231:245	ER phosphorylation	228:245	ER phosphorylation	228:245	Binding of GDNF to GFRA1 triggers RET signaling leading to ER phosphorylation and estrogen-independent transcriptional activation of ER-dependent genes.
30040982	7	63	theme	ER	1006:1007	arg1	inhibitors					981:990	inhibitors	981:990	inhibitors of RET and/or ER	981:1007	Finally, we demonstrated ST3GAL1 knockdown augments anti-cancer efficacy of inhibitors of RET and/or ER.
30040982	1	64	theme	estrogen	121:128	arg1	receptor					130:137	estrogen receptor	121:137	estrogen receptor	121:137	GFRA1 and RET are overexpressed in estrogen receptor (ER)-positive breast cancers.
30040982	8	65	with	patients	1092:1099	arg1	cancer					1124:1129	late stage breast cancer	1106:1129	late stage breast cancer	1106:1129	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	4	66	theme	cancer	596:601	arg1	cells					603:607	ER-positive breast cancer cells	577:607	ER-positive breast cancer cells	577:607	We found GFRA1 to be a substrate of ST3GAL1-mediated O-linked sialylation, which is crucial to GDNF-induced signaling in ER-positive breast cancer cells.
30040982	0	67	theme	breast	65:70	arg1	cells					79:83	breast cancer cells	65:83	breast cancer cells	65:83	Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells.
30040982	6	68	theme	positive	815:822	arg1	loop					833:836	a positive feedback loop	813:836	a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers	813:902	Moreover, GDNF induced transcription of ST3GAL1, revealing a positive feedback loop regulating ST3GAL1 and GDNF/GFRA1/RET signaling in breast cancers.
30040982	8	69	theme	high	1135:1138	arg1	expression					1140:1149	high expression	1135:1149	high expression of both ST3GAL1 and GFRA1	1135:1175	Moreover, high expression of ST3GAL1 was associated with poor clinical outcome in patients with late stage breast cancer and high expression of both ST3GAL1 and GFRA1 adversely impacted outcome in those with high grade tumors.
30040982	7	70	theme	RET	995:997	arg1	inhibitors					981:990	inhibitors	981:990	inhibitors of RET and/or ER	981:1007	Finally, we demonstrated ST3GAL1 knockdown augments anti-cancer efficacy of inhibitors of RET and/or ER.
30023808	4	0	theme	novel	917:921	arg1	NPs					942:944	novel Fe3O4-PEI-pMaltose NPs	917:944	novel Fe3O4-PEI-pMaltose NPs	917:944	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	5	1	theme	glycosylation	1265:1277	arg1	sites					1279:1283	476 glycosylation sites	1261:1283	476 glycosylation sites	1261:1283	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	4	2	theme	NPs	942:944	arg1	performance					902:912	The above-mentioned excellent performance	872:912	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs	872:944	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	3	3	theme	large	795:799	arg1	capacity					809:816	large binding capacity	795:816	large binding capacity (200 mg/g)	795:827	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	3	theme	large	795:799	arg1	mg/g					823:826	200 mg/g	819:826	200 mg/g	819:826	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	6	4	theme	as-synthesized	1328:1341	arg1	NPs					1362:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	3	5	theme	high	680:683	arg1	selectivity					685:695	high selectivity	680:695	high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest)	680:761	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	4	6	theme	above-mentioned	876:890	arg1	performance					902:912	The above-mentioned excellent performance	872:912	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs	872:944	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	2	7	theme	high	320:323	arg1	polyethylenimine					337:352	the high hydrophilic polyethylenimine	316:352	the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose	316:471	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	6	8	theme	proteome	1603:1610	arg1	analysis					1612:1619	N-glycosylation proteome analysis	1587:1619	N-glycosylation proteome analysis of complex biological samples	1587:1649	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	1	9	theme	biomedical	247:256	arg1	sciences					258:265	the biomedical sciences	243:265	the biomedical sciences	243:265	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	4	10	theme	maltose	973:979	arg1	brushes					989:995	maltose polymer brushes	973:995	maltose polymer brushes	973:995	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	5	11	theme	cell	1148:1151	arg1	digest					1176:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	2	12	theme	polymaltose	365:375	arg1	brushes					385:391	polymaltose polymer brushes	365:391	polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose	365:471	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	6	13	theme	huge	1569:1572	arg1	potential					1574:1582	a huge potential	1567:1582	a huge potential	1567:1582	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	4	14	theme	brushes	989:995	arg1	graft					964:968	graft	964:968	graft of maltose polymer brushes and efficient assembly strategy	964:1027	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	6	15	theme	high	1401:1404	arg1	capacity					1414:1421	high binding capacity	1401:1421	high binding capacity	1401:1421	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	3	16	theme	HRP	720:722	arg1	digest					755:760	bovine serum albumin (BSA) digest	728:760	bovine serum albumin (BSA) digest	728:760	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	16	theme	HRP	720:722	arg1	1:100					698:702	1:100	698:702	1:100	698:702	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	16	theme	HRP	720:722	arg1	ratios					710:715	mass ratios	705:715	mass ratios of HRP	705:722	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	1	17	theme	particular	271:280	arg1	research					292:299	particular biomarker research	271:299	particular biomarker research	271:299	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	1	18	from	sciences	258:265	arg1	important					230:238	important	230:238	important	230:238	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	5	19	gly	glycoproteins	1243:1255	arg1	glycoproteins					1243:1255	323 different glycoproteins	1229:1255	323 different glycoproteins	1229:1255	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	1	20	from	research	292:299	arg1	important					230:238	important	230:238	important	230:238	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	6	21	gly	N-glycosylation	1587:1601	arg1	samples					1643:1649	complex biological samples	1624:1649	complex biological samples	1624:1649	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	3	22	theme	albumin	741:747	arg1	digest					755:760	bovine serum albumin (BSA) digest	728:760	bovine serum albumin (BSA) digest	728:760	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	1	23	theme	complex	192:198	arg1	solutions					211:219	complex biological solutions	192:219	complex biological solutions	192:219	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	3	24	theme	Fe3O4-PEI-pMaltose	569:586	arg1	NPs					588:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs	539:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs	539:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	25	theme	enrichment	839:848	arg1	%					868:868	above 85%	860:868	above 85%	860:868	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	25	theme	enrichment	839:848	arg1	recovery					850:857	high enrichment recovery	834:857	high enrichment recovery (above 85%)	834:869	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	26	theme	bovine	728:733	arg1	BSA					750:752	BSA	750:752	BSA	750:752	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	26	theme	bovine	728:733	arg1	albumin					741:747	bovine serum albumin	728:747	bovine serum albumin (BSA) digest	728:760	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	1	27	from	important	230:238	arg1	research					292:299	particular biomarker research	271:299	particular biomarker research	271:299	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	1	27	from	important	230:238	arg1	sciences					258:265	the biomedical sciences	243:265	the biomedical sciences	243:265	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	6	28	contain	possessing	1367:1376	arg1	NPs					1362:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	28	contain	possessing	1367:1376	arg2	performance					1388:1398	excellent performance	1378:1398	excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure	1378:1559	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	29	theme	detection	1446:1454	arg1	limit					1456:1460	low detection limit	1442:1460	low detection limit	1442:1460	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	5	30	theme	renal	1132:1136	arg1	cell					1148:1151	renal mesangial cell	1132:1151	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	4	31	theme	efficient	1001:1009	arg1	strategy					1020:1027	efficient assembly strategy	1001:1027	efficient assembly strategy	1001:1027	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	0	32	theme	N-Linked	114:121	arg1	Glycopeptides					123:135	N-Linked Glycopeptides	114:135	N-Linked Glycopeptides	114:135	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	4	33	theme	strategy	1020:1027	arg1	graft					964:968	graft	964:968	graft of maltose polymer brushes and efficient assembly strategy	964:1027	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	6	34	theme	good	1424:1427	arg1	selectivity					1429:1439	good selectivity	1424:1439	good selectivity	1424:1439	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	5	35	theme	Fe3O4-PEI-pMaltose	1040:1057	arg1	NPs					1059:1061	Fe3O4-PEI-pMaltose NPs	1040:1061	Fe3O4-PEI-pMaltose NPs	1040:1061	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	6	36	theme	high	1463:1466	arg1	recovery					1479:1486	high enrichment recovery	1463:1486	high enrichment recovery	1463:1486	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	0	37	theme	Maltose-Functionalized	0:21	arg1	Nanoparticles					44:56	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles	0:56	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.	0:136	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	5	38	gly	glycopeptides	1107:1119	arg2	glycopeptides					1107:1119	glycopeptides	1107:1119	glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest	1107:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	5	38	gly	glycopeptides	1107:1119	arg1	digest					1176:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	2	39	theme	simple	509:514	arg1	modification					525:536	a simple two-step modification	507:536	a simple two-step modification	507:536	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	0	40	theme	Magnetic	35:42	arg1	Nanoparticles					44:56	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles	0:56	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.	0:136	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	3	41	theme	glycopeptides	655:667	arg1	enrichment					632:641	the enrichment	628:641	the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%)	628:869	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	1	42	theme	Efficient	138:146	arg1	glycoproteins/glycopeptides					159:185	Efficient enrichment glycoproteins/glycopeptides	138:185	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions	138:219	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	1	43	theme	biological	200:209	arg1	solutions					211:219	complex biological solutions	192:219	complex biological solutions	192:219	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	3	44	theme	obtained	543:550	arg1	NPs					588:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs	539:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs	539:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	5	45	theme	N-linked	1192:1199	arg1	glycopeptides					1201:1213	449 N-linked glycopeptides	1188:1213	449 N-linked glycopeptides	1188:1213	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	6	46	contain	have	1562:1565	arg1	NPs					1362:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	46	contain	have	1562:1565	arg2	potential					1574:1582	a huge potential	1567:1582	a huge potential	1567:1582	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	5	47	used	utilized	1076:1083	arg2	NPs					1059:1061	Fe3O4-PEI-pMaltose NPs	1040:1061	Fe3O4-PEI-pMaltose NPs	1040:1061	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	6	48	theme	enrichment	1468:1477	arg1	recovery					1479:1486	high enrichment recovery	1463:1486	high enrichment recovery	1463:1486	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	5	49	link	N-linked	1192:1199	arg1	glycopeptides					1201:1213	449 N-linked glycopeptides	1188:1213	449 N-linked glycopeptides	1188:1213	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	3	50	theme	detection	768:776	arg1	limit					778:782	low detection limit	764:782	low detection limit (10 fmol)	764:792	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	50	theme	detection	768:776	arg1	fmol					788:791	10 fmol	785:791	10 fmol	785:791	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	2	51	theme	Fe3O4	417:421	arg1	nanoparticles					423:435	magnetic Fe3O4 nanoparticles	408:435	magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose	408:471	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	2	51	theme	Fe3O4	417:421	arg1	NPs					438:440	NPs	438:440	NPs	438:440	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	6	52	theme	biological	1632:1641	arg1	samples					1643:1649	complex biological samples	1624:1649	complex biological samples	1624:1649	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	1	53	theme	biomarker	282:290	arg1	research					292:299	particular biomarker research	271:299	particular biomarker research	271:299	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	6	54	theme	preparation	1539:1549	arg1	procedure					1551:1559	a facile preparation procedure	1530:1559	a facile preparation procedure	1530:1559	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	5	55	theme	476	1261:1263	arg1	sites					1279:1283	476 glycosylation sites	1261:1283	476 glycosylation sites	1261:1283	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	6	56	theme	Fe3O4-PEI-pMaltose	1343:1360	arg1	NPs					1362:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	the as-synthesized Fe3O4-PEI-pMaltose NPs	1324:1364	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	4	57	theme	Fe3O4-PEI-pMaltose	923:940	arg1	NPs					942:944	novel Fe3O4-PEI-pMaltose NPs	917:944	novel Fe3O4-PEI-pMaltose NPs	917:944	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	3	58	theme	binding	801:807	arg1	capacity					809:816	large binding capacity	795:816	large binding capacity (200 mg/g)	795:827	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	58	theme	binding	801:807	arg1	mg/g					823:826	200 mg/g	819:826	200 mg/g	819:826	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	2	59	theme	hydrophilic	325:335	arg1	polyethylenimine					337:352	the high hydrophilic polyethylenimine	316:352	the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose	316:471	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	6	60	theme	N-glycosylation	1587:1601	arg1	analysis					1612:1619	N-glycosylation proteome analysis	1587:1619	N-glycosylation proteome analysis of complex biological samples	1587:1649	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	4	61	theme	excellent	892:900	arg1	performance					902:912	The above-mentioned excellent performance	872:912	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs	872:944	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	1	62	gly	glycoproteins/glycopeptides	159:185	arg1	solutions					211:219	complex biological solutions	192:219	complex biological solutions	192:219	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	1	62	gly	glycoproteins/glycopeptides	159:185	arg2	glycoproteins/glycopeptides					159:185	Efficient enrichment glycoproteins/glycopeptides	138:185	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions	138:219	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	2	63	theme	polymer	377:383	arg1	brushes					385:391	polymaltose polymer brushes	365:391	polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose	365:471	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	6	64	dep	performance	1388:1398	arg1	separation					1507:1516	easy magnetic separation	1493:1516	easy magnetic separation	1493:1516	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	64	dep	performance	1388:1398	arg1	recovery					1479:1486	high enrichment recovery	1463:1486	high enrichment recovery	1463:1486	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	64	dep	performance	1388:1398	arg1	capacity					1414:1421	high binding capacity	1401:1421	high binding capacity	1401:1421	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	64	dep	performance	1388:1398	arg1	selectivity					1429:1439	good selectivity	1424:1439	good selectivity	1424:1439	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	64	dep	performance	1388:1398	arg1	limit					1456:1460	low detection limit	1442:1460	low detection limit	1442:1460	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	6	65	theme	binding	1406:1412	arg1	capacity					1414:1421	high binding capacity	1401:1421	high binding capacity	1401:1421	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	3	66	link	N-linked	646:653	arg1	glycopeptides					655:667	N-linked glycopeptides	646:667	N-linked glycopeptides	646:667	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	66	link	N-linked	646:653	arg1	capacity					809:816	large binding capacity	795:816	large binding capacity (200 mg/g)	795:827	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	66	link	N-linked	646:653	arg1	limit					778:782	low detection limit	764:782	low detection limit (10 fmol)	764:792	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	66	link	N-linked	646:653	arg1	selectivity					685:695	high selectivity	680:695	high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest)	680:761	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	66	link	N-linked	646:653	arg1	recovery					850:857	high enrichment recovery	834:857	high enrichment recovery (above 85%)	834:869	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	67	theme	high	834:837	arg1	%					868:868	above 85%	860:868	above 85%	860:868	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	67	theme	high	834:837	arg1	recovery					850:857	high enrichment recovery	834:857	high enrichment recovery (above 85%)	834:869	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	6	68	theme	low	1442:1444	arg1	limit					1456:1460	low detection limit	1442:1460	low detection limit	1442:1460	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	3	69	theme	mass	705:708	arg1	ratios					710:715	mass ratios	705:715	mass ratios of HRP	705:722	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	1	70	theme	enrichment	148:157	arg1	glycoproteins/glycopeptides					159:185	Efficient enrichment glycoproteins/glycopeptides	138:185	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions	138:219	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	6	71	theme	excellent	1378:1386	arg1	performance					1388:1398	excellent performance	1378:1398	excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure	1378:1559	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	5	72	theme	human	1126:1130	arg1	digest					1176:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	3	73	theme	serum	735:739	arg1	BSA					750:752	BSA	750:752	BSA	750:752	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	73	theme	serum	735:739	arg1	albumin					741:747	bovine serum albumin	728:747	bovine serum albumin (BSA) digest	728:760	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	5	74	gly	glycopeptides	1201:1213	arg2	glycopeptides					1201:1213	449 N-linked glycopeptides	1188:1213	449 N-linked glycopeptides	1188:1213	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	0	75	theme	Selective	90:98	arg1	Enrichment					100:109	Highly Selective Enrichment	83:109	Highly Selective Enrichment of N-Linked Glycopeptides	83:135	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	5	76	theme	mesangial	1138:1146	arg1	cell					1148:1151	renal mesangial cell	1132:1151	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	6	77	theme	samples	1643:1649	arg1	analysis					1612:1619	N-glycosylation proteome analysis	1587:1619	N-glycosylation proteome analysis of complex biological samples	1587:1649	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	3	78	dep	selectivity	685:695	arg1	digest					755:760	bovine serum albumin (BSA) digest	728:760	bovine serum albumin (BSA) digest	728:760	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	78	dep	selectivity	685:695	arg1	1:100					698:702	1:100	698:702	1:100	698:702	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	78	dep	selectivity	685:695	arg1	ratios					710:715	mass ratios	705:715	mass ratios of HRP	705:722	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	6	79	theme	complex	1624:1630	arg1	samples					1643:1649	complex biological samples	1624:1649	complex biological samples	1624:1649	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	3	80	gly	glycopeptides	655:667	arg2	capacity					809:816	large binding capacity	795:816	large binding capacity (200 mg/g)	795:827	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	80	gly	glycopeptides	655:667	arg2	glycopeptides					655:667	N-linked glycopeptides	646:667	N-linked glycopeptides	646:667	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	80	gly	glycopeptides	655:667	arg2	selectivity					685:695	high selectivity	680:695	high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest)	680:761	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	80	gly	glycopeptides	655:667	arg2	recovery					850:857	high enrichment recovery	834:857	high enrichment recovery (above 85%)	834:869	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	80	gly	glycopeptides	655:667	arg2	limit					778:782	low detection limit	764:782	low detection limit (10 fmol)	764:792	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	6	81	theme	easy	1493:1496	arg1	separation					1507:1516	easy magnetic separation	1493:1516	easy magnetic separation	1493:1516	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	0	82	theme	Glycopeptides	123:135	arg1	Enrichment					100:109	Highly Selective Enrichment	83:109	Highly Selective Enrichment of N-Linked Glycopeptides	83:135	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	3	83	theme	outstanding	602:612	arg1	advantages					614:623	outstanding advantages	602:623	outstanding advantages	602:623	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	1	84	from	solutions	211:219	arg1	glycoproteins/glycopeptides					159:185	Efficient enrichment glycoproteins/glycopeptides	138:185	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions	138:219	Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research.
30023808	4	85	theme	assembly	1011:1018	arg1	strategy					1020:1027	efficient assembly strategy	1001:1027	efficient assembly strategy	1001:1027	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	5	86	gly	glycosylation	1265:1277	arg2	sites					1279:1283	476 glycosylation sites	1261:1283	476 glycosylation sites	1261:1283	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	0	87	theme	Hydrophilic	23:33	arg1	Nanoparticles					44:56	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles	0:56	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.	0:136	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	5	88	theme	tryptic	1168:1174	arg1	digest					1176:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	human renal mesangial cell (HRMC, 200 μg) tryptic digest	1126:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	6	89	theme	magnetic	1498:1505	arg1	separation					1507:1516	easy magnetic separation	1493:1516	easy magnetic separation	1493:1516	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
30023808	5	90	theme	different	1233:1241	arg1	glycoproteins					1243:1255	323 different glycoproteins	1229:1255	323 different glycoproteins	1229:1255	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	2	91	theme	two-step	516:523	arg1	modification					525:536	a simple two-step modification	507:536	a simple two-step modification	507:536	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	0	92	theme	Polymer	63:69	arg1	Brushes					71:77	Polymer Brushes	63:77	Polymer Brushes	63:77	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	0	93	with	Nanoparticles	44:56	arg1	Brushes					71:77	Polymer Brushes	63:77	Polymer Brushes	63:77	Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.
30023808	3	94	theme	superhydrophilic	552:567	arg1	NPs					588:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs	539:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs	539:590	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	5	95	from	digest	1176:1181	arg1	glycopeptides					1107:1119	glycopeptides	1107:1119	glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest	1107:1181	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	4	96	theme	polymer	981:987	arg1	brushes					989:995	maltose polymer brushes	973:995	maltose polymer brushes	973:995	The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy.
30023808	3	97	theme	low	764:766	arg1	limit					778:782	low detection limit	764:782	low detection limit (10 fmol)	764:792	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	97	theme	low	764:766	arg1	fmol					788:791	10 fmol	785:791	10 fmol	785:791	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	2	98	theme	magnetic	408:415	arg1	nanoparticles					423:435	magnetic Fe3O4 nanoparticles	408:435	magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose	408:471	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	2	98	theme	magnetic	408:415	arg1	NPs					438:440	NPs	438:440	NPs	438:440	In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification.
30023808	5	99	dep	cell	1148:1151	arg1	HRMC					1154:1157	HRMC	1154:1157	HRMC	1154:1157	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	5	99	dep	cell	1148:1151	arg1	μg					1164:1165	200 μg	1160:1165	200 μg	1160:1165	Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 μg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified.
30023808	3	100	theme	N-linked	646:653	arg1	glycopeptides					655:667	N-linked glycopeptides	646:667	N-linked glycopeptides	646:667	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	100	theme	N-linked	646:653	arg1	capacity					809:816	large binding capacity	795:816	large binding capacity (200 mg/g)	795:827	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	100	theme	N-linked	646:653	arg1	limit					778:782	low detection limit	764:782	low detection limit (10 fmol)	764:792	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	100	theme	N-linked	646:653	arg1	selectivity					685:695	high selectivity	680:695	high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest)	680:761	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	3	100	theme	N-linked	646:653	arg1	recovery					850:857	high enrichment recovery	834:857	high enrichment recovery (above 85%)	834:869	The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%).
30023808	6	101	theme	facile	1532:1537	arg1	preparation					1539:1549	a facile preparation	1530:1549	a facile preparation procedure	1530:1559	It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.
29842980	7	0	from	differences	1206:1216	arg1	protein					1231:1237	their VP7 protein	1221:1237	their VP7 protein	1221:1237	Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein.
29842980	6	1	theme	intergenogroup	958:971	arg1	reassortment					973:984	intergenogroup reassortment	958:984	intergenogroup reassortment	958:984	The analyses revealed intergenogroup reassortment in G3P[4] strains (among Wa and DS-1-like genogroup) whereas G3P[8] strains were authentic Wa-like.
29842980	1	2	theme	A	249:249	arg1	RVA					262:264	RVA	262:264	RVA	262:264	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	2	theme	A	249:249	arg1	one					268:270	one	268:270	one	268:270	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	2	theme	A	249:249	arg1	rotavirus					251:259	group- A rotavirus	242:259	group- A rotavirus (RVA)	242:265	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	2	theme	A	249:249	arg1	causes					285:290	the major causes	275:290	the major causes of childhood gastroenteritis	275:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	11	3	theme	strains	1757:1763	arg1	monitoring					1727:1736	Continuous monitoring	1716:1736	Continuous monitoring of circulating RVA strains in endemic settings like India	1716:1794	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	4	4	from	strain	593:598	arg1	2014-2015					611:619	2014-2015	611:619	2014-2015	611:619	G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%).
29842980	9	5	theme	RotaTeq	1525:1531	arg1	vaccine					1533:1539	RotaTeq vaccine	1525:1539	RotaTeq vaccine	1525:1539	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	11	6	theme	genotypes	1899:1907	arg1	emergence					1870:1878	the emergence	1866:1878	the emergence of new reassortant genotypes in addition to assessing vaccine efficacy	1866:1949	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	1	7	theme	new	158:160	arg1	strains					162:168	new strains	158:168	new strains	158:168	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	6	8	theme	DS-1-like	1018:1026	arg1	genogroup					1028:1036	DS-1-like genogroup	1018:1036	DS-1-like genogroup	1018:1036	The analyses revealed intergenogroup reassortment in G3P[4] strains (among Wa and DS-1-like genogroup) whereas G3P[8] strains were authentic Wa-like.
29842980	3	9	theme	acute	502:506	arg1	gastroenteritis					508:522	acute gastroenteritis	502:522	acute gastroenteritis	502:522	Stool samples from children (n = 3048) with acute gastroenteritis were tested of which 38.7% were RVA positive.
29842980	11	10	from	period	1848:1853	arg1	important					1809:1817	important	1809:1817	important	1809:1817	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	5	11	theme	strains	927:933	arg1	emergence					861:869	emergence	861:869	emergence	861:869	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	5	11	theme	strains	927:933	arg1	constellation					883:895	genetic constellation	875:895	genetic constellation	875:895	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	5	12	theme	past	702:705	arg1	decade					707:712	the past decade G3 strains were not observed in this region	698:756	the past decade G3 strains were not observed in this region	698:756	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	9	13	theme	circulating	1568:1578	arg1	strains					1583:1589	the currently circulating G3 strains	1554:1589	the currently circulating G3 strains	1554:1589	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	8	14	theme	acid	1304:1307	arg1	position					1309:1316	87 amino acid position	1295:1316	87 amino acid position	1295:1316	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	5	15	located	observed	734:741	arg1	region					751:756	this region	746:756	this region	746:756	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	5	15	located	observed	734:741	arg2	strains					717:723	G3 strains	714:723	G3 strains	714:723	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	10	16	theme	circulating	1665:1675	arg1	constellations					1700:1713	the circulating heterogeneous genotype constellations	1661:1713	the circulating heterogeneous genotype constellations	1661:1713	The study is important as efficiency of rotavirus vaccine depends on the circulating heterogeneous genotype constellations.
29842980	5	17	theme	G3	714:715	arg1	strains					717:723	G3 strains	714:723	G3 strains	714:723	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	0	18	from	India	48:52	arg1	spread					12:17	spread	12:17	spread	12:17	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	0	18	from	India	48:52	arg1	Upsurge					0:6	Upsurge	0:6	Upsurge	0:6	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	11	19	dep	assessing	1924:1932	arg1	addition					1912:1919	addition	1912:1919	addition	1912:1919	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	0	20	theme	genomic	125:131	arg1	constellation					133:145	Wa-like genomic constellation	117:145	Wa-like genomic constellation	117:145	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	1	21	from	shift	174:178	arg1	genotypes					209:217	predominantly circulating genotypes	183:217	predominantly circulating genotypes	183:217	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	7	22	theme	VP7	1227:1229	arg1	protein					1231:1237	their VP7 protein	1221:1237	their VP7 protein	1221:1237	Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein.
29842980	6	23	theme	authentic	1067:1075	arg1	Wa-like					1077:1083	authentic Wa-like	1067:1083	authentic Wa-like	1067:1083	The analyses revealed intergenogroup reassortment in G3P[4] strains (among Wa and DS-1-like genogroup) whereas G3P[8] strains were authentic Wa-like.
29842980	9	24	theme	glycoprotein	1448:1459	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	24	theme	glycoprotein	1448:1459	arg1	site					1418:1421	additional N-linked glycosylation site	1384:1421	additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1384:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	5	25	theme	human	918:922	arg1	strains					927:933	these circulating human G3 strains	900:933	these circulating human G3 strains	900:933	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	11	26	theme	new	1883:1885	arg1	genotypes					1899:1907	new reassortant genotypes	1883:1907	new reassortant genotypes	1883:1907	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	5	27	theme	genome	778:783	arg1	sequencing					785:794	whole genome sequencing	772:794	whole genome sequencing of representative strains	772:820	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	10	28	theme	genotype	1691:1698	arg1	constellations					1700:1713	the circulating heterogeneous genotype constellations	1661:1713	the circulating heterogeneous genotype constellations	1661:1713	The study is important as efficiency of rotavirus vaccine depends on the circulating heterogeneous genotype constellations.
29842980	9	29	theme	N-linked	1395:1402	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	29	theme	N-linked	1395:1402	arg1	site					1418:1421	additional N-linked glycosylation site	1384:1421	additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1384:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	30	from	acid	1432:1435	arg1	Presence					1372:1379	Presence	1372:1379	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1372:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	30	from	acid	1432:1435	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	30	from	acid	1432:1435	arg1	site					1418:1421	additional N-linked glycosylation site	1384:1421	additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1384:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	0	31	from	spread	12:17	arg1	2014-2016					55:63	2014-2016	55:63	2014-2016	55:63	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	0	31	from	spread	12:17	arg1	India					48:52	India	48:52	India	48:52	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	1	32	theme	gastroenteritis	305:319	arg1	causes					285:290	the major causes	275:290	the major causes of childhood gastroenteritis	275:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	9	33	theme	site	1418:1421	arg1	Presence					1372:1379	Presence	1372:1379	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1372:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	0	34	from	Upsurge	0:6	arg1	2014-2016					55:63	2014-2016	55:63	2014-2016	55:63	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	0	34	from	Upsurge	0:6	arg1	India					48:52	India	48:52	India	48:52	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	9	35	theme	amino	1426:1430	arg1	acid					1432:1435	amino acid 283	1426:1439	amino acid 283	1426:1439	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	0	36	theme	genome	72:77	arg1	analyses					79:86	Full genome analyses	67:86	G3 rotaviruses in Eastern India (2014-2016): Full genome analyses	22:86	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	9	37	from	epitope	1498:1504	arg1	G3					1518:1519	G3	1518:1519	G3	1518:1519	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	37	from	epitope	1498:1504	arg1	VP7					1513:1515	the VP7	1509:1515	the VP7 (G3) of RotaTeq vaccine	1509:1539	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	2	38	theme	circulating	402:412	arg1	strains					418:424	circulating RVA strains	402:424	circulating RVA strains	402:424	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	9	39	gly	glycosylation	1404:1416	arg2	site					1418:1421	additional N-linked glycosylation site	1384:1421	additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1384:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	39	gly	glycosylation	1404:1416	arg2	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	39	gly	glycosylation	1404:1416	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	39	gly	glycosylation	1404:1416	arg2	acid					1432:1435	amino acid 283	1426:1439	amino acid 283	1426:1439	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	40	theme	VP7	1444:1446	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	11	41	theme	pre-	1822:1825	arg1	period					1848:1853	pre- and post-vaccination period	1822:1853	pre- and post-vaccination period	1822:1853	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	5	42	theme	strains	814:820	arg1	sequencing					785:794	whole genome sequencing	772:794	whole genome sequencing of representative strains	772:820	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	0	43	theme	G3	22:23	arg1	rotaviruses					25:35	G3 rotaviruses	22:35	G3 rotaviruses in Eastern India (2014-2016): Full genome analyses	22:86	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	9	44	link	N-linked	1395:1402	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	44	link	N-linked	1395:1402	arg1	site					1418:1421	additional N-linked glycosylation site	1384:1421	additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1384:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	5	45	theme	genetic	875:881	arg1	constellation					883:895	genetic constellation	875:895	genetic constellation	875:895	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	8	46	theme	wild-type	1272:1280	arg1	threonine					1282:1290	the wild-type threonine	1268:1290	the wild-type threonine	1268:1290	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	11	47	theme	circulating	1741:1751	arg1	strains					1757:1763	circulating RVA strains	1741:1763	circulating RVA strains	1741:1763	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	1	48	theme	major	279:283	arg1	causes					285:290	the major causes	275:290	the major causes of childhood gastroenteritis	275:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	9	49	theme	neutralizing	1485:1496	arg1	epitope					1498:1504	the major neutralizing epitope	1475:1504	the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine	1475:1539	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	2	50	from	India	372:376	arg1	surveillance					347:358	diarrheal disease surveillance	329:358	diarrheal disease surveillance at Kolkata, India (2014-2016)	329:388	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	9	51	gly	glycoprotein	1448:1459	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	5	52	dep	decade	707:712	arg1	observed					734:741	observed	734:741	were not observed in this region	725:756	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	7	53	theme	polymorphic	1139:1149	arg1	strains					1128:1134	Kolkata G3 strains	1117:1134	Kolkata G3 strains as polymorphic	1117:1149	Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein.
29842980	8	54	theme	amino	1298:1302	arg1	position					1309:1316	87 amino acid position	1295:1316	87 amino acid position	1295:1316	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	11	55	theme	endemic	1768:1774	arg1	settings					1776:1783	endemic settings	1768:1783	endemic settings like India	1768:1794	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	5	56	theme	emergence	861:869	arg1	phenomenon					847:856	the phenomenon	843:856	the phenomenon of emergence and genetic constellation of these circulating human G3 strains	843:933	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	2	57	theme	diarrheal	329:337	arg1	surveillance					347:358	diarrheal disease surveillance	329:358	diarrheal disease surveillance at Kolkata, India (2014-2016)	329:388	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	1	58	theme	group-	242:247	arg1	RVA					262:264	RVA	262:264	RVA	262:264	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	58	theme	group-	242:247	arg1	one					268:270	one	268:270	one	268:270	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	58	theme	group-	242:247	arg1	rotavirus					251:259	group- A rotavirus	242:259	group- A rotavirus (RVA)	242:265	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	58	theme	group-	242:247	arg1	causes					285:290	the major causes	275:290	the major causes of childhood gastroenteritis	275:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	7	59	theme	Kolkata	1117:1123	arg1	strains					1128:1134	Kolkata G3 strains	1117:1134	Kolkata G3 strains as polymorphic	1117:1149	Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein.
29842980	0	60	dep	rotaviruses	25:35	arg1	analyses					79:86	Full genome analyses	67:86	G3 rotaviruses in Eastern India (2014-2016): Full genome analyses	22:86	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	1	61	theme	rotavirus	251:259	arg1	characteristics					223:237	characteristics	223:237	characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis	223:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	61	theme	rotavirus	251:259	arg1	shift					174:178	shift	174:178	shift in predominantly circulating genotypes	174:217	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	61	theme	rotavirus	251:259	arg1	Advent					148:153	Advent	148:153	Advent of new strains	148:168	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	11	62	theme	reassortant	1887:1897	arg1	genotypes					1899:1907	new reassortant genotypes	1883:1907	new reassortant genotypes	1883:1907	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	2	63	theme	RVA	414:416	arg1	strains					418:424	circulating RVA strains	402:424	circulating RVA strains	402:424	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	9	64	theme	vaccine	1533:1539	arg1	G3					1518:1519	G3	1518:1519	G3	1518:1519	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	64	theme	vaccine	1533:1539	arg1	VP7					1513:1515	the VP7	1509:1515	the VP7 (G3) of RotaTeq vaccine	1509:1539	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	65	from	Presence	1372:1379	arg1	acid					1432:1435	amino acid 283	1426:1439	amino acid 283	1426:1439	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	11	66	theme	vaccine	1934:1940	arg1	efficacy					1942:1949	vaccine efficacy	1934:1949	vaccine efficacy	1934:1949	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	1	67	theme	strains	162:168	arg1	characteristics					223:237	characteristics	223:237	characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis	223:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	67	theme	strains	162:168	arg1	shift					174:178	shift	174:178	shift in predominantly circulating genotypes	174:217	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	67	theme	strains	162:168	arg1	Advent					148:153	Advent	148:153	Advent of new strains	148:168	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	4	68	theme	predominant	581:591	arg1	%					605:605	65.3%	601:605	65.3%	601:605	G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%).
29842980	4	68	theme	predominant	581:591	arg1	G1					570:571	G1	570:571	G1	570:571	G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%).
29842980	4	68	theme	predominant	581:591	arg1	strain					593:598	the predominant strain	577:598	the predominant strain (65.3%)	577:606	G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%).
29842980	10	69	theme	rotavirus	1632:1640	arg1	vaccine					1642:1648	rotavirus vaccine	1632:1648	rotavirus vaccine	1632:1648	The study is important as efficiency of rotavirus vaccine depends on the circulating heterogeneous genotype constellations.
29842980	10	70	theme	vaccine	1642:1648	arg1	efficiency					1618:1627	efficiency	1618:1627	efficiency of rotavirus vaccine	1618:1648	The study is important as efficiency of rotavirus vaccine depends on the circulating heterogeneous genotype constellations.
29842980	0	71	theme	Wa-like	117:123	arg1	constellation					133:145	Wa-like genomic constellation	117:145	Wa-like genomic constellation	117:145	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	10	72	theme	heterogeneous	1677:1689	arg1	constellations					1700:1713	the circulating heterogeneous genotype constellations	1661:1713	the circulating heterogeneous genotype constellations	1661:1713	The study is important as efficiency of rotavirus vaccine depends on the circulating heterogeneous genotype constellations.
29842980	9	73	theme	G3	1580:1581	arg1	strains					1583:1589	the currently circulating G3 strains	1554:1589	the currently circulating G3 strains	1554:1589	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	11	74	from	important	1809:1817	arg1	period					1848:1853	pre- and post-vaccination period	1822:1853	pre- and post-vaccination period	1822:1853	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	11	75	theme	Continuous	1716:1725	arg1	monitoring					1727:1736	Continuous monitoring	1716:1736	Continuous monitoring of circulating RVA strains in endemic settings like India	1716:1794	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	11	76	theme	post-vaccination	1831:1846	arg1	period					1848:1853	pre- and post-vaccination period	1822:1853	pre- and post-vaccination period	1822:1853	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	5	77	theme	circulating	906:916	arg1	strains					927:933	these circulating human G3 strains	900:933	these circulating human G3 strains	900:933	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	5	78	theme	whole	772:776	arg1	sequencing					785:794	whole genome sequencing	772:794	whole genome sequencing of representative strains	772:820	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	8	79	theme	isoleucine	1351:1360	arg1	mutation					1362:1369	an isoleucine mutation	1348:1369	an isoleucine mutation	1348:1369	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	7	80	theme	Phylogenetic	1086:1097	arg1	analysis					1099:1106	Phylogenetic analysis	1086:1106	Phylogenetic analysis	1086:1106	Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein.
29842980	5	81	theme	G3	924:925	arg1	strains					927:933	these circulating human G3 strains	900:933	these circulating human G3 strains	900:933	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	3	82	theme	which	539:543	arg1	positive					560:567	positive	560:567	positive	560:567	Stool samples from children (n = 3048) with acute gastroenteritis were tested of which 38.7% were RVA positive.
29842980	9	83	theme	additional	1384:1393	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	83	theme	additional	1384:1393	arg1	site					1418:1421	additional N-linked glycosylation site	1384:1421	additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1384:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	2	84	from	shift	393:397	arg1	strains					418:424	circulating RVA strains	402:424	circulating RVA strains	402:424	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	1	85	theme	childhood	295:303	arg1	gastroenteritis					305:319	childhood gastroenteritis	295:319	childhood gastroenteritis	295:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	9	86	theme	glycosylation	1404:1416	arg1	glycoprotein					1448:1459	VP7 glycoprotein	1444:1459	VP7 glycoprotein	1444:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	9	86	theme	glycosylation	1404:1416	arg1	site					1418:1421	additional N-linked glycosylation site	1384:1421	additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein	1384:1459	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	3	87	from	children	477:484	arg1	samples					464:470	Stool samples	458:470	Stool samples from children (n = 3048) with acute gastroenteritis	458:522	Stool samples from children (n = 3048) with acute gastroenteritis were tested of which 38.7% were RVA positive.
29842980	0	88	theme	Full	67:70	arg1	analyses					79:86	Full genome analyses	67:86	G3 rotaviruses in Eastern India (2014-2016): Full genome analyses	22:86	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	2	89	dep	G1P[8	431:435	arg1	G3P[8					441:445	G3P[8	441:445	G3P[8	441:445	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	2	89	dep	G1P[8	431:435	arg1	to					438:439	to	438:439	to	438:439	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	1	90	from	Advent	148:153	arg1	genotypes					209:217	predominantly circulating genotypes	183:217	predominantly circulating genotypes	183:217	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	6	91	theme	G3P[4	989:993	arg1	strains					996:1002	G3P[4] strains	989:1002	G3P[4] strains	989:1002	The analyses revealed intergenogroup reassortment in G3P[4] strains (among Wa and DS-1-like genogroup) whereas G3P[8] strains were authentic Wa-like.
29842980	7	92	theme	antigenic	1196:1204	arg1	differences					1206:1216	antigenic differences	1196:1216	antigenic differences in their VP7 protein	1196:1237	Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein.
29842980	0	93	from	rotaviruses	25:35	arg1	2014-2016					55:63	2014-2016	55:63	2014-2016	55:63	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	0	93	from	rotaviruses	25:35	arg1	India					48:52	India	48:52	India	48:52	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	11	94	from	monitoring	1727:1736	arg1	settings					1776:1783	endemic settings	1768:1783	endemic settings like India	1768:1794	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	5	95	theme	representative	799:812	arg1	strains					814:820	representative strains	799:820	representative strains	799:820	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	0	96	theme	rotaviruses	25:35	arg1	spread					12:17	spread	12:17	spread	12:17	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	0	96	theme	rotaviruses	25:35	arg1	Upsurge					0:6	Upsurge	0:6	Upsurge	0:6	Upsurge and spread of G3 rotaviruses in Eastern India (2014-2016): Full genome analyses reveals heterogeneity within Wa-like genomic constellation.
29842980	8	97	theme	sub-clusters	1251:1262	arg1	One					1240:1242	One	1240:1242	One	1240:1242	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	8	97	theme	sub-clusters	1251:1262	arg1	sub-clusters					1251:1262	the sub-clusters	1247:1262	the sub-clusters	1247:1262	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	3	98	with	children	477:484	arg1	gastroenteritis					508:522	acute gastroenteritis	502:522	acute gastroenteritis	502:522	Stool samples from children (n = 3048) with acute gastroenteritis were tested of which 38.7% were RVA positive.
29842980	5	99	theme	constellation	883:895	arg1	phenomenon					847:856	the phenomenon	843:856	the phenomenon of emergence and genetic constellation of these circulating human G3 strains	843:933	In the past decade G3 strains were not observed in this region, we conducted whole genome sequencing of representative strains to gain insight into the phenomenon of emergence and genetic constellation of these circulating human G3 strains.
29842980	2	100	from	G1P[8	431:435	arg1	shift					393:397	a shift	391:397	a shift in circulating RVA strains from G1P[8] to G3P[8]	391:446	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	8	101	contain	had	1264:1266	arg1	One					1240:1242	One	1240:1242	One	1240:1242	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	8	101	contain	had	1264:1266	arg1	sub-clusters					1251:1262	the sub-clusters	1247:1262	the sub-clusters	1247:1262	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	8	101	contain	had	1264:1266	arg2	threonine					1282:1290	the wild-type threonine	1268:1290	the wild-type threonine	1268:1290	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	11	102	theme	RVA	1753:1755	arg1	strains					1757:1763	circulating RVA strains	1741:1763	circulating RVA strains	1741:1763	Continuous monitoring of circulating RVA strains in endemic settings like India is therefore important in pre- and post-vaccination period to monitor the emergence of new reassortant genotypes in addition to assessing vaccine efficacy.
29842980	1	103	theme	causes	285:290	arg1	one					268:270	one	268:270	one	268:270	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	103	theme	causes	285:290	arg1	rotavirus					251:259	group- A rotavirus	242:259	group- A rotavirus (RVA)	242:265	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	1	103	theme	causes	285:290	arg1	causes					285:290	the major causes	275:290	the major causes of childhood gastroenteritis	275:319	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	9	104	theme	major	1479:1483	arg1	epitope					1498:1504	the major neutralizing epitope	1475:1504	the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine	1475:1539	Presence of additional N-linked glycosylation site at amino acid 283 of VP7 glycoprotein suggests that the major neutralizing epitope on the VP7 (G3) of RotaTeq vaccine differs from the currently circulating G3 strains.
29842980	4	105	theme	preponderant	666:677	arg1	strain					679:684	the preponderant strain	662:684	the preponderant strain (44.6%)	662:692	G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%).
29842980	4	105	theme	preponderant	666:677	arg1	%					691:691	44.6%	687:691	44.6%	687:691	G1 was the predominant strain (65.3%) in 2014-2015 whereas in late 2015 and 2016, G3 became the preponderant strain (44.6%).
29842980	2	106	theme	disease	339:345	arg1	surveillance					347:358	diarrheal disease surveillance	329:358	diarrheal disease surveillance at Kolkata, India (2014-2016)	329:388	During diarrheal disease surveillance at Kolkata, India (2014-2016), a shift in circulating RVA strains from G1P[8] to G3P[8] was seen.
29842980	1	107	theme	circulating	197:207	arg1	genotypes					209:217	predominantly circulating genotypes	183:217	predominantly circulating genotypes	183:217	Advent of new strains and shift in predominantly circulating genotypes are characteristics of group- A rotavirus (RVA), one of the major causes of childhood gastroenteritis.
29842980	7	108	theme	G3	1125:1126	arg1	strains					1128:1134	Kolkata G3 strains	1117:1134	Kolkata G3 strains as polymorphic	1117:1149	Phylogenetic analysis revealed Kolkata G3 strains as polymorphic and thus they formed two sub-clusters due to antigenic differences in their VP7 protein.
29842980	8	109	contain	had	1344:1346	arg2	mutation					1362:1369	an isoleucine mutation	1348:1369	an isoleucine mutation	1348:1369	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	8	109	contain	had	1344:1346	arg1	sub-cluster					1332:1342	another sub-cluster	1324:1342	another sub-cluster	1324:1342	One of the sub-clusters had the wild-type threonine at 87 amino acid position while another sub-cluster had an isoleucine mutation.
29842980	3	110	theme	Stool	458:462	arg1	samples					464:470	Stool samples	458:470	Stool samples from children (n = 3048) with acute gastroenteritis	458:522	Stool samples from children (n = 3048) with acute gastroenteritis were tested of which 38.7% were RVA positive.
28591079	8	0	theme	humor	1131:1135	arg1	sequences					1137:1145	Aqueous humor sequences	1123:1145	Aqueous humor sequences	1123:1145	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	2	1	with	individuals	369:379	arg1	uveitis					386:392	uveitis	386:392	uveitis	386:392	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.
28591079	1	2	theme	disease	292:298	arg1	pathogenesis					257:268	the pathogenesis	253:268	the pathogenesis of HIV-associated eye disease	253:298	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	5	3	theme	Sequence	690:697	arg1	analyses					699:706	Sequence analyses	690:706	Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy	690:762	Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy evaluated relationships between HIV in plasma and aqueous humor.
28591079	10	4	from	population	1714:1723	arg1	variants					1679:1686	variants	1679:1686	variants from each patient's viral population	1679:1723	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	10	4	from	population	1714:1723	arg1	subset					1669:1674	a small subset	1661:1674	a small subset of variants from each patient's viral population	1661:1723	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	4	5	theme	single-genome	578:590	arg1	amplification					592:604	single-genome amplification	578:604	single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing	578:687	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	8	6	theme	median	1157:1162	arg1	diversity					1172:1180	lower median genetic diversity	1151:1180	lower median genetic diversity compared with plasma across all patients	1151:1221	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	6	7	theme	15	870:871	arg1	humor					895:899	15 (range: 9-18) aqueous humor	870:899	15 (range: 9-18) aqueous humor	870:899	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	4	8	theme	Sanger	671:676	arg1	sequencing					678:687	bidirectional Sanger sequencing	657:687	bidirectional Sanger sequencing	657:687	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	8	9	contain	had	1147:1149	arg2	divergence					1236:1245	similar divergence	1228:1245	similar divergence	1228:1245	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	8	9	contain	had	1147:1149	arg2	diversity					1172:1180	lower median genetic diversity	1151:1180	lower median genetic diversity compared with plasma across all patients	1151:1221	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	8	9	contain	had	1147:1149	arg1	sequences					1137:1145	Aqueous humor sequences	1123:1145	Aqueous humor sequences	1123:1145	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	6	10	theme	plasma	859:864	arg1	sequences					901:909	20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences	841:909	20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences	841:909	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	10	11	dep	compartmentalization	1546:1565	arg1	the					1532:1534	the	1532:1534	the	1532:1534	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	7	12	theme	aqueous	1076:1082	arg1	humor					1084:1088	aqueous humor	1076:1088	aqueous humor	1076:1088	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	10	13	theme	blood	1612:1616	arg1	sequences					1618:1626	blood sequences	1612:1626	blood sequences	1612:1626	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	2	14	theme	individuals	369:379	arg1	series					320:325	A prospective case series	301:325	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis	301:392	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.
28591079	7	15	theme	predicted-N-linked-glycosylation	982:1013	arg1	sites					1015:1019	predicted-N-linked-glycosylation sites	982:1019	predicted-N-linked-glycosylation sites	982:1019	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	6	16	theme	sequences	901:909	arg1	median					831:836	A median	829:836	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences	829:909	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	7	17	theme	receptor	1041:1048	arg1	type					1050:1053	C-X-C chemokine receptor type 4	1025:1055	C-X-C chemokine receptor type 4	1025:1055	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	7	18	theme	sequences	967:975	arg1	frequencies					952:962	The frequencies	948:962	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4	948:1055	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	7	18	theme	sequences	967:975	arg1	comparable					1062:1071	comparable	1062:1071	comparable	1062:1071	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	1	19	theme	env	118:120	arg1	sequences					122:130	HIV-1 env sequences	112:130	HIV-1 env sequences from the eye	112:143	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	6	20	theme	aqueous	887:893	arg1	humor					895:899	15 (range: 9-18) aqueous humor	870:899	15 (range: 9-18) aqueous humor	870:899	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	7	21	theme	C-X-C	1025:1029	arg1	type					1050:1053	C-X-C chemokine receptor type 4	1025:1055	C-X-C chemokine receptor type 4	1025:1055	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	3	22	theme	aqueous	457:463	arg1	humor					465:469	ocular aqueous humor	450:469	ocular aqueous humor	450:469	RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers.
28591079	4	23	dep	HXB2	533:536	arg1	6990-7668					539:547	6990-7668	539:547	6990-7668	539:547	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	5	24	from	HIV	796:798	arg1	plasma					803:808	plasma	803:808	plasma	803:808	Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy evaluated relationships between HIV in plasma and aqueous humor.
28591079	5	24	from	HIV	796:798	arg1	humor					822:826	aqueous humor	814:826	aqueous humor	814:826	Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy evaluated relationships between HIV in plasma and aqueous humor.
28591079	9	25	theme	humor	1282:1286	arg1	sequences					1292:1300	Aqueous humor HIV sequences	1274:1300	Aqueous humor HIV sequences	1274:1300	Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
28591079	3	26	dep	reverse	475:481	arg1	transcribed					483:493	transcribed	483:493	was reverse transcribed using random hexamers	471:515	RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers.
28591079	3	27	theme	blood	433:437	arg1	plasma					439:444	blood plasma	433:444	blood plasma	433:444	RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers.
28591079	0	28	theme	Genetic	0:6	arg1	analyses					8:15	Genetic analyses	0:15	Genetic analyses of HIV env	0:26	Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals.
28591079	10	29	theme	viral	1708:1712	arg1	population					1714:1723	each patient's viral population	1693:1723	each patient's viral population	1693:1723	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	10	30	with	individuals	1488:1498	arg1	uveitis					1505:1511	uveitis	1505:1511	uveitis attributed to HIV	1505:1529	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	6	31	dep	20	841:842	arg1	range					845:849	range	845:849	range: 13-22	845:856	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	2	32	theme	other	407:411	arg1	pathogens					413:421	other pathogens	407:421	other pathogens	407:421	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.
28591079	0	33	theme	env	24:26	arg1	analyses					8:15	Genetic analyses	0:15	Genetic analyses of HIV env	0:26	Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals.
28591079	1	34	theme	HIV-associated	273:286	arg1	disease					292:298	HIV-associated eye disease	273:298	HIV-associated eye disease	273:298	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	7	35	gly	predicted-N-linked-glycosylation	982:1013	arg2	sites					1015:1019	predicted-N-linked-glycosylation sites	982:1019	predicted-N-linked-glycosylation sites	982:1019	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	10	36	theme	universal	1536:1544	arg1	compartmentalization					1546:1565	universal compartmentalization	1536:1565	universal compartmentalization	1536:1565	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	10	37	theme	eye	1734:1736	arg1	tissues					1738:1744	the eye tissues	1730:1744	the eye tissues	1730:1744	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	9	38	theme	Critchlow	1356:1364	arg1	coefficient					1378:1388	Critchlow correlation coefficient	1356:1388	Critchlow correlation coefficient	1356:1388	Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
28591079	6	39	dep	range	845:849	arg1	13-22					852:856	13-22	852:856	13-22	852:856	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	3	40	from	humor	465:469	arg1	RNA					424:426	RNA	424:426	RNA from blood plasma and ocular aqueous humor	424:469	RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers.
28591079	2	41	theme	prospective	303:313	arg1	series					320:325	A prospective case series	301:325	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis	301:392	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.
28591079	10	42	theme	limited	1759:1765	arg1	selection					1774:1782	limited immune selection	1759:1782	limited immune selection	1759:1782	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	2	43	theme	antiretroviral-naive	348:367	arg1	individuals					369:379	five HIV-infected antiretroviral-naive individuals	330:379	five HIV-infected antiretroviral-naive individuals with uveitis	330:392	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.
28591079	6	44	dep	15	870:871	arg1	range					874:878	range	874:878	range: 9-18	874:884	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	3	45	from	plasma	439:444	arg1	RNA					424:426	RNA	424:426	RNA from blood plasma and ocular aqueous humor	424:469	RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers.
28591079	3	46	theme	random	501:506	arg1	hexamers					508:515	random hexamers	501:515	random hexamers	501:515	RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers.
28591079	8	47	theme	Aqueous	1123:1129	arg1	humor					1131:1135	Aqueous humor	1123:1135	Aqueous humor sequences	1123:1145	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	6	48	dep	range	874:878	arg1	9-18					881:884	9-18	881:884	9-18	881:884	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	9	49	theme	nearest-neighbor	1413:1428	arg1	statistic					1430:1438	nearest-neighbor statistic	1413:1438	nearest-neighbor statistic	1413:1438	Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
28591079	7	50	from	comparable	1062:1071	arg1	humor					1084:1088	aqueous humor	1076:1088	aqueous humor	1076:1088	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	7	50	from	comparable	1062:1071	arg1	plasma					1094:1099	plasma	1094:1099	plasma	1094:1099	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	10	51	theme	eye	1594:1596	arg1	compartmentalization					1546:1565	universal compartmentalization	1536:1565	universal compartmentalization	1536:1565	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	10	51	theme	eye	1594:1596	arg1	diversity					1581:1589	decreased diversity	1571:1589	decreased diversity	1571:1589	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	10	52	theme	immune	1767:1772	arg1	selection					1774:1782	limited immune selection	1759:1782	limited immune selection	1759:1782	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	8	53	theme	lower	1151:1155	arg1	diversity					1172:1180	lower median genetic diversity	1151:1180	lower median genetic diversity compared with plasma across all patients	1151:1221	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	4	54	theme	bidirectional	657:669	arg1	sequencing					678:687	bidirectional Sanger sequencing	657:687	bidirectional Sanger sequencing	657:687	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	10	55	theme	time-limited	1637:1648	arg1	passage					1650:1656	time-limited passage	1637:1656	time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection	1637:1782	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	9	56	theme	Fixation	1445:1452	arg1	index					1454:1458	Fixation index	1445:1458	Fixation index	1445:1458	Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
28591079	8	57	theme	genetic	1164:1170	arg1	diversity					1172:1180	lower median genetic diversity	1151:1180	lower median genetic diversity compared with plasma across all patients	1151:1221	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	8	58	theme	similar	1228:1234	arg1	divergence					1236:1245	similar divergence	1228:1245	similar divergence	1228:1245	Aqueous humor sequences had lower median genetic diversity compared with plasma across all patients, but similar divergence, in four of five patients.
28591079	10	59	theme	inflammatory	1796:1807	arg1	uveitis					1809:1815	the inflammatory uveitis	1792:1815	the inflammatory uveitis	1792:1815	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	1	60	theme	individuals	172:182	arg1	blood					163:167	the blood	159:167	the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease	159:298	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	4	61	theme	chain	630:634	arg1	reaction					636:643	nested polymerase chain reaction	612:643	nested polymerase chain reaction followed by bidirectional Sanger sequencing	612:687	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	10	62	theme	small	1663:1667	arg1	subset					1669:1674	a small subset	1661:1674	a small subset of variants from each patient's viral population	1661:1723	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	7	63	theme	chemokine	1031:1039	arg1	type					1050:1053	C-X-C chemokine receptor type 4	1025:1055	C-X-C chemokine receptor type 4	1025:1055	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	4	64	theme	C2-V5	526:530	arg1	env					522:524	HIV env C2-V5	518:530	HIV env C2-V5 (HXB2: 6990-7668) sequences	518:558	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	1	65	theme	HIV-1	112:116	arg1	sequences					122:130	HIV-1 env sequences	112:130	HIV-1 env sequences from the eye	112:143	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	9	66	theme	Aqueous	1274:1280	arg1	humor					1282:1286	Aqueous humor	1274:1286	Aqueous humor HIV sequences	1274:1300	Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
28591079	6	67	theme	humor	895:899	arg1	sequences					901:909	20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences	841:909	20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences	841:909	A median of 20 (range: 13-22) plasma and 15 (range: 9-18) aqueous humor sequences were generated from each individual.
28591079	0	68	theme	antiretroviral-naive	55:74	arg1	individuals					76:86	antiretroviral-naive individuals	55:86	antiretroviral-naive individuals	55:86	Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals.
28591079	7	69	with	sequences	967:975	arg1	type					1050:1053	C-X-C chemokine receptor type 4	1025:1055	C-X-C chemokine receptor type 4	1025:1055	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	7	69	with	sequences	967:975	arg1	sites					1015:1019	predicted-N-linked-glycosylation sites	982:1019	predicted-N-linked-glycosylation sites	982:1019	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	4	70	theme	HIV	518:520	arg1	env					522:524	HIV env C2-V5	518:530	HIV env C2-V5 (HXB2: 6990-7668) sequences	518:558	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	4	71	dep	env	522:524	arg1	HXB2					533:536	HXB2	533:536	HXB2: 6990-7668	533:547	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	9	72	theme	HIV	1288:1290	arg1	sequences					1292:1300	Aqueous humor HIV sequences	1274:1300	Aqueous humor HIV sequences	1274:1300	Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
28591079	1	73	from	eye	141:143	arg1	sequences					122:130	HIV-1 env sequences	112:130	HIV-1 env sequences from the eye	112:143	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	10	74	theme	antiretroviral-naive	1467:1486	arg1	individuals					1488:1498	antiretroviral-naive individuals	1467:1498	antiretroviral-naive individuals with uveitis attributed to HIV	1467:1529	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	10	75	theme	variants	1679:1686	arg1	subset					1669:1674	a small subset	1661:1674	a small subset of variants from each patient's viral population	1661:1723	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	5	76	theme	aqueous	814:820	arg1	humor					822:826	aqueous humor	814:826	aqueous humor	814:826	Sequence analyses by Geneious, Geno2Pheno, N-GLYCOSITE, DIVEIN, and HyPhy evaluated relationships between HIV in plasma and aqueous humor.
28591079	10	77	theme	subset	1669:1674	arg1	passage					1650:1656	time-limited passage	1637:1656	time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection	1637:1782	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	0	78	theme	HIV	20:22	arg1	env					24:26	HIV env	20:26	HIV env	20:26	Genetic analyses of HIV env associated with uveitis in antiretroviral-naive individuals.
28591079	7	79	from	humor	1084:1088	arg1	frequencies					952:962	The frequencies	948:962	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4	948:1055	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	7	79	from	humor	1084:1088	arg1	comparable					1062:1071	comparable	1062:1071	comparable	1062:1071	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	1	80	with	individuals	172:182	arg1	uveitis					189:195	uveitis	189:195	uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease	189:298	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	7	81	from	plasma	1094:1099	arg1	frequencies					952:962	The frequencies	948:962	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4	948:1055	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	7	81	from	plasma	1094:1099	arg1	comparable					1062:1071	comparable	1062:1071	comparable	1062:1071	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	3	82	theme	ocular	450:455	arg1	humor					465:469	ocular aqueous humor	450:469	ocular aqueous humor	450:469	RNA from blood plasma and ocular aqueous humor was reverse transcribed using random hexamers.
28591079	7	83	theme	patients	1113:1120	arg1	humor					1084:1088	aqueous humor	1076:1088	aqueous humor	1076:1088	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	7	83	theme	patients	1113:1120	arg1	plasma					1094:1099	plasma	1094:1099	plasma	1094:1099	The frequencies of sequences with predicted-N-linked-glycosylation sites and C-X-C chemokine receptor type 4 were comparable in aqueous humor and plasma of all five patients.
28591079	1	84	theme	eye	288:290	arg1	disease					292:298	HIV-associated eye disease	273:298	HIV-associated eye disease	273:298	To analyze and compare HIV-1 env sequences from the eye to those from the blood of individuals with uveitis attributed to HIV with the goal of gaining insight into the pathogenesis of HIV-associated eye disease.
28591079	10	85	from	subset	1669:1674	arg1	population					1714:1723	each patient's viral population	1693:1723	each patient's viral population	1693:1723	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	2	86	theme	case	315:318	arg1	series					320:325	A prospective case series	301:325	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis	301:392	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.
28591079	9	87	theme	correlation	1366:1376	arg1	coefficient					1378:1388	Critchlow correlation coefficient	1356:1388	Critchlow correlation coefficient	1356:1388	Aqueous humor HIV sequences were compartmentalized from plasma across subjects by Critchlow correlation coefficient, Slatkin and Maddison, nearest-neighbor statistic, and Fixation index.
28591079	4	88	theme	env	522:524	arg1	sequences					550:558	HIV env C2-V5 (HXB2: 6990-7668) sequences	518:558	HIV env C2-V5 (HXB2: 6990-7668) sequences	518:558	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	4	89	theme	polymerase	619:628	arg1	reaction					636:643	nested polymerase chain reaction	612:643	nested polymerase chain reaction followed by bidirectional Sanger sequencing	612:687	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	10	90	theme	decreased	1571:1579	arg1	diversity					1581:1589	decreased diversity	1571:1589	decreased diversity	1571:1589	Among antiretroviral-naive individuals with uveitis attributed to HIV, the universal compartmentalization and decreased diversity of eye compared with blood sequences suggests time-limited passage of a small subset of variants from each patient's viral population into the eye tissues, followed by limited immune selection despite the inflammatory uveitis.
28591079	4	91	theme	nested	612:617	arg1	reaction					636:643	nested polymerase chain reaction	612:643	nested polymerase chain reaction followed by bidirectional Sanger sequencing	612:687	HIV env C2-V5 (HXB2: 6990-7668) sequences were generated by single-genome amplification using nested polymerase chain reaction followed by bidirectional Sanger sequencing.
28591079	2	92	theme	HIV-infected	335:346	arg1	individuals					369:379	five HIV-infected antiretroviral-naive individuals	330:379	five HIV-infected antiretroviral-naive individuals with uveitis	330:392	A prospective case series of five HIV-infected antiretroviral-naive individuals with uveitis negative for other pathogens.
28922609	7	0	theme	serum	1412:1416	arg1	concentrations					1418:1431	the serum concentrations	1408:1431	the serum concentrations of 160 proteins in samples from FAC and FAP patients	1408:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	4	1	theme	disease	807:813	arg1	biomarkers					793:802	no definitive biomarkers	779:802	no definitive biomarkers of disease	779:813	FAC and FAP are pathologies that can be challenging to diagnose as there are no definitive biomarkers of disease; moreover, disease-specific measures of progression are lacking, and treatment options are limited.
28922609	13	2	located	found	2463:2467	arg2	associations					2445:2456	no associations	2442:2456	no associations	2442:2456	Predicted protein-protein associations in FAC were seen for reaction, binding, and activation processes; no associations were found in FAP.
28922609	13	2	located	found	2463:2467	arg1	FAP					2472:2474	FAP	2472:2474	FAP	2472:2474	Predicted protein-protein associations in FAC were seen for reaction, binding, and activation processes; no associations were found in FAP.
28922609	3	3	theme	amyloid	637:643	arg1	FAP					661:663	FAP	661:663	FAP	661:663	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	3	theme	amyloid	637:643	arg1	ATTR					445:448	ATTR	445:448	ATTR	445:448	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	3	theme	amyloid	637:643	arg1	polyneuropathy					645:658	familial amyloid polyneuropathy	628:658	familial amyloid polyneuropathy (FAP)	628:664	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	13	4	from	associations	2363:2374	arg1	FAC					2379:2381	FAC	2379:2381	FAC	2379:2381	Predicted protein-protein associations in FAC were seen for reaction, binding, and activation processes; no associations were found in FAP.
28922609	14	5	theme	proteins	2661:2668	arg1	levels					2643:2648	the circulating levels	2627:2648	the circulating levels of several proteins including TTR	2627:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	10	6	theme	proteins	1906:1913	arg1	concentrations					1842:1855	concentrations	1842:1855	concentrations as well as interactions and functions of several proteins	1842:1913	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	10	6	theme	proteins	1906:1913	arg1	functions					1885:1893	functions	1885:1893	functions	1885:1893	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	10	6	theme	proteins	1906:1913	arg1	interactions					1868:1879	interactions	1868:1879	interactions	1868:1879	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	7	7	used	used	1392:1395	arg2	MRM-MS					1334:1339	MRM-MS	1334:1339	MRM-MS	1334:1339	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	7	used	used	1392:1395	arg2	technique					1354:1362	a powerful technique	1343:1362	a powerful technique in profiling proteomes	1343:1385	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	7	used	used	1392:1395	arg2	spectrometry					1320:1331	Multiple-reaction monitoring mass spectrometry	1286:1331	Multiple-reaction monitoring mass spectrometry (MRM-MS)	1286:1340	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	13	8	theme	Predicted	2337:2345	arg1	associations					2363:2374	Predicted protein-protein associations	2337:2374	Predicted protein-protein associations in FAC	2337:2381	Predicted protein-protein associations in FAC were seen for reaction, binding, and activation processes; no associations were found in FAP.
28922609	1	9	theme	fibrils	265:271	arg1	deposition					243:252	extracellular deposition	229:252	extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues	229:314	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
28922609	7	10	theme	powerful	1345:1352	arg1	technique					1354:1362	a powerful technique	1343:1362	a powerful technique in profiling proteomes	1343:1385	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	10	theme	powerful	1345:1352	arg1	spectrometry					1320:1331	Multiple-reaction monitoring mass spectrometry	1286:1331	Multiple-reaction monitoring mass spectrometry (MRM-MS)	1286:1340	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	9	11	from	differences	1729:1739	arg1	proteins					1774:1781	the serum proteins	1764:1781	the serum proteins	1764:1781	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	9	11	from	differences	1729:1739	arg1	192					1751:1753	192	1751:1753	192	1751:1753	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	12	12	dep	FAC	2195:2197	arg1	site					2224:2227	secreted, glycosylation site	2200:2227	site	2224:2227	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	15	13	theme	proteins	2713:2720	arg1	identification					2689:2702	The identification	2685:2702	The identification of serum proteins unique to FAC and FAP	2685:2742	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	9	14	theme	serum	1768:1772	arg1	proteins					1774:1781	the serum proteins	1764:1781	the serum proteins	1764:1781	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	3	15	theme	clinical	682:689	arg1	phenotype					691:699	the clinical phenotype	678:699	the clinical phenotype	678:699	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	6	16	theme	FAP	1266:1268	arg1	types					1270:1274	FAP types	1266:1274	FAP types	1266:1274	In this study, the goal was to investigate serum proteomic features unique to FAC and FAP types of ATTRm.
28922609	14	17	theme	phenotype-associated	2592:2611	arg1	variations					2613:2622	ATTRm phenotype-associated variations	2586:2622	ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR	2586:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	4	18	theme	disease-specific	826:841	arg1	measures					843:850	disease-specific measures	826:850	disease-specific measures of progression	826:865	FAC and FAP are pathologies that can be challenging to diagnose as there are no definitive biomarkers of disease; moreover, disease-specific measures of progression are lacking, and treatment options are limited.
28922609	7	19	theme	monitoring	1304:1313	arg1	technique					1354:1362	a powerful technique	1343:1362	a powerful technique in profiling proteomes	1343:1385	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	19	theme	monitoring	1304:1313	arg1	MRM-MS					1334:1339	MRM-MS	1334:1339	MRM-MS	1334:1339	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	19	theme	monitoring	1304:1313	arg1	spectrometry					1320:1331	Multiple-reaction monitoring mass spectrometry	1286:1331	Multiple-reaction monitoring mass spectrometry (MRM-MS)	1286:1340	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	6	20	theme	unique	1248:1253	arg1	features					1239:1246	serum proteomic features	1223:1246	serum proteomic features unique to FAC and FAP types of ATTRm	1223:1283	In this study, the goal was to investigate serum proteomic features unique to FAC and FAP types of ATTRm.
28922609	5	21	theme	disease	975:981	arg1	indicators					961:970	sensitive and specific indicators	938:970	sensitive and specific indicators of disease	938:981	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	3	22	from	mutations	528:536	arg1	gene					549:552	the TTR gene	541:552	the TTR gene	541:552	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	8	23	from	sera	1538:1541	arg1	data					1512:1515	data	1512:1515	data from healthy control sera obtained from individuals matched to age (≥60 years), gender (male), and race (Caucasian)	1512:1631	Results were compared to data from healthy control sera obtained from individuals matched to age (≥60 years), gender (male), and race (Caucasian).
28922609	15	24	theme	serum	2707:2711	arg1	proteins					2713:2720	serum proteins	2707:2720	serum proteins unique to FAC and FAP	2707:2742	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	15	25	theme	unique	2722:2727	arg1	proteins					2713:2720	serum proteins	2707:2720	serum proteins unique to FAC and FAP	2707:2742	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	5	26	theme	FAP	1148:1150	arg1	mechanisms					1168:1177	FAP pathobiological mechanisms	1148:1177	FAP pathobiological mechanisms	1148:1177	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	5	27	theme	amyloid	1056:1062	arg1	progression					1064:1074	amyloid progression	1056:1074	amyloid progression	1056:1074	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	6	28	theme	proteomic	1229:1237	arg1	features					1239:1246	serum proteomic features	1223:1246	serum proteomic features unique to FAC and FAP types of ATTRm	1223:1283	In this study, the goal was to investigate serum proteomic features unique to FAC and FAP types of ATTRm.
28922609	1	29	theme	circulating	149:159	arg1	protein					161:167	a plasma circulating protein	140:167	normally a plasma circulating protein	131:167	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
28922609	1	29	theme	circulating	149:159	arg1	Transthyretin					110:122	Transthyretin	110:122	Transthyretin (TTR)	110:128	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
28922609	4	30	theme	treatment	884:892	arg1	options					894:900	treatment options	884:900	treatment options	884:900	FAC and FAP are pathologies that can be challenging to diagnose as there are no definitive biomarkers of disease; moreover, disease-specific measures of progression are lacking, and treatment options are limited.
28922609	14	31	theme	several	2653:2659	arg1	TTR					2680:2682	TTR	2680:2682	TTR	2680:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	14	31	theme	several	2653:2659	arg1	proteins					2661:2668	several proteins	2653:2668	several proteins including TTR	2653:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	7	32	theme	FAP	1473:1475	arg1	patients					1477:1484	FAC and FAP patients	1465:1484	patients	1477:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	11	33	theme	Annotated	2030:2038	arg1	clustering					2051:2060	Annotated functional clustering	2030:2060	Annotated functional clustering	2030:2060	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	0	34	from	Phenotype	53:61	arg1	Amyloidosis					89:99	Familial Transthyretin Amyloidosis	66:99	Familial Transthyretin Amyloidosis (ATTRm)	66:107	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	0	34	from	Phenotype	53:61	arg1	ATTRm					102:106	ATTRm	102:106	ATTRm	102:106	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	5	35	theme	pathobiological	1152:1166	arg1	mechanisms					1168:1177	FAP pathobiological mechanisms	1148:1177	FAP pathobiological mechanisms	1148:1177	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	13	36	theme	protein-protein	2347:2361	arg1	associations					2363:2374	Predicted protein-protein associations	2337:2374	Predicted protein-protein associations in FAC	2337:2381	Predicted protein-protein associations in FAC were seen for reaction, binding, and activation processes; no associations were found in FAP.
28922609	9	37	dep	192	1751:1753	arg1	%					1758:1758	56%	1756:1758	56%	1756:1758	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	11	38	theme	common	2131:2136	arg1	peptide					2114:2120	signal peptide	2107:2120	signal peptide	2107:2120	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	38	theme	common	2131:2136	arg1	signal					2095:2100	signal	2095:2100	signal	2095:2100	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	38	theme	common	2131:2136	arg1	terms					2125:2129	terms	2125:2129	terms common to FAC and FAP	2125:2151	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	38	theme	common	2131:2136	arg1	region					2087:2092	extracellular region	2073:2092	extracellular region	2073:2092	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	12	39	theme	N-linked	2230:2237	arg1	glycosylation					2240:2252	glycosylation	2240:2252	glycosylation	2240:2252	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	13	40	theme	activation	2420:2429	arg1	processes					2431:2439	activation processes	2420:2439	activation processes	2420:2439	Predicted protein-protein associations in FAC were seen for reaction, binding, and activation processes; no associations were found in FAP.
28922609	0	41	theme	Serum	0:4	arg1	Variability					16:26	Serum Proteomic Variability	0:26	Serum Proteomic Variability	0:26	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	14	42	theme	proteomic	2513:2521	arg1	differences					2523:2533	significant proteomic differences	2501:2533	significant proteomic differences between ATTRm patient and control sera	2501:2572	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	0	43	theme	Familial	66:73	arg1	Amyloidosis					89:99	Familial Transthyretin Amyloidosis	66:99	Familial Transthyretin Amyloidosis (ATTRm)	66:107	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	0	43	theme	Familial	66:73	arg1	ATTRm					102:106	ATTRm	102:106	ATTRm	102:106	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	5	44	theme	specific	952:959	arg1	indicators					961:970	sensitive and specific indicators	938:970	sensitive and specific indicators of disease	938:981	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	15	45	theme	prognostic	2768:2777	arg1	utility					2779:2785	diagnostic and prognostic utility	2753:2785	diagnostic and prognostic utility	2753:2785	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	9	46	theme	samples	1688:1694	arg1	analyses					1644:1651	Proteomic analyses	1634:1651	Proteomic analyses of ATTRm (FAC and FAP) and control samples	1634:1694	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	3	47	theme	amyloid	596:602	arg1	cardiomyopathy					604:617	familial amyloid cardiomyopathy	587:617	familial amyloid cardiomyopathy (FAC)	587:623	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	47	theme	amyloid	596:602	arg1	ATTR					445:448	ATTR	445:448	ATTR	445:448	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	47	theme	amyloid	596:602	arg1	FAC					620:622	FAC	620:622	FAC	620:622	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	2	48	theme	TTR-associated	332:345	arg1	ATTR					360:363	ATTR	360:363	ATTR	360:363	Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated.
28922609	2	48	theme	TTR-associated	332:345	arg1	amyloidoses					347:357	TTR-associated amyloidoses	332:357	TTR-associated amyloidoses (ATTR)	332:364	Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated.
28922609	10	49	theme	several	1898:1904	arg1	proteins					1906:1913	several proteins	1898:1913	several proteins	1898:1913	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	3	50	theme	familial	628:635	arg1	FAP					661:663	FAP	661:663	FAP	661:663	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	50	theme	familial	628:635	arg1	ATTR					445:448	ATTR	445:448	ATTR	445:448	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	50	theme	familial	628:635	arg1	polyneuropathy					645:658	familial amyloid polyneuropathy	628:658	familial amyloid polyneuropathy (FAP)	628:664	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	11	51	theme	extracellular	2073:2085	arg1	peptide					2114:2120	signal peptide	2107:2120	signal peptide	2107:2120	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	51	theme	extracellular	2073:2085	arg1	signal					2095:2100	signal	2095:2100	signal	2095:2100	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	51	theme	extracellular	2073:2085	arg1	region					2087:2092	extracellular region	2073:2092	extracellular region	2073:2092	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	51	theme	extracellular	2073:2085	arg1	terms					2125:2129	terms	2125:2129	terms common to FAC and FAP	2125:2151	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	5	52	contain	has	983:985	arg2	potential					991:999	the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms	987:1177	the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms	987:1177	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	5	52	contain	has	983:985	arg1	discovery					925:933	the discovery	921:933	the discovery of sensitive and specific indicators of disease	921:981	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	5	53	theme	sensitive	938:946	arg1	indicators					961:970	sensitive and specific indicators	938:970	sensitive and specific indicators of disease	938:981	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	8	54	theme	healthy	1522:1528	arg1	sera					1538:1541	healthy control sera	1522:1541	healthy control sera obtained from individuals matched to age (≥60 years), gender (male), and race (Caucasian)	1522:1631	Results were compared to data from healthy control sera obtained from individuals matched to age (≥60 years), gender (male), and race (Caucasian).
28922609	6	55	theme	serum	1223:1227	arg1	features					1239:1246	serum proteomic features	1223:1246	serum proteomic features unique to FAC and FAP types of ATTRm	1223:1283	In this study, the goal was to investigate serum proteomic features unique to FAC and FAP types of ATTRm.
28922609	3	56	theme	TTR	485:487	arg1	proteins					489:496	amyloid-forming variant TTR proteins	461:496	amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene	461:552	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	56	theme	TTR	485:487	arg1	ATTRm					499:503	ATTRm	499:503	ATTRm	499:503	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	15	57	theme	diagnostic	2753:2762	arg1	utility					2779:2785	diagnostic and prognostic utility	2753:2785	diagnostic and prognostic utility	2753:2785	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	1	58	theme	amyloid	257:263	arg1	fibrils					265:271	amyloid fibrils	257:271	amyloid fibrils usually targeted to heart or nerve tissues	257:314	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
28922609	14	59	theme	circulating	2631:2641	arg1	levels					2643:2648	the circulating levels	2627:2648	the circulating levels of several proteins including TTR	2627:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	7	60	theme	profiling	1367:1375	arg1	proteomes					1377:1385	profiling proteomes	1367:1385	profiling proteomes	1367:1385	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	12	61	theme	disulfide	2166:2174	arg1	bond					2176:2179	disulfide bond	2166:2179	disulfide bond	2166:2179	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	3	62	theme	amyloid-forming	461:475	arg1	proteins					489:496	amyloid-forming variant TTR proteins	461:496	amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene	461:552	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	62	theme	amyloid-forming	461:475	arg1	ATTRm					499:503	ATTRm	499:503	ATTRm	499:503	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	12	63	theme	sequence	2287:2294	arg1	variant					2296:2302	sequence variant	2287:2302	sequence variant	2287:2302	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	14	64	from	variations	2613:2622	arg1	levels					2643:2648	the circulating levels	2627:2648	the circulating levels of several proteins including TTR	2627:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	4	65	theme	definitive	782:791	arg1	biomarkers					793:802	no definitive biomarkers	779:802	no definitive biomarkers of disease	779:813	FAC and FAP are pathologies that can be challenging to diagnose as there are no definitive biomarkers of disease; moreover, disease-specific measures of progression are lacking, and treatment options are limited.
28922609	11	66	theme	signal	2107:2112	arg1	signal					2095:2100	signal	2095:2100	signal	2095:2100	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	66	theme	signal	2107:2112	arg1	region					2087:2092	extracellular region	2073:2092	extracellular region	2073:2092	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	66	theme	signal	2107:2112	arg1	terms					2125:2129	terms	2125:2129	terms common to FAC and FAP	2125:2151	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	11	66	theme	signal	2107:2112	arg1	peptide					2114:2120	signal peptide	2107:2120	signal peptide	2107:2120	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	3	67	theme	point	522:526	arg1	mutations					528:536	point mutations	522:536	point mutations in the TTR gene	522:552	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	4	68	theme	progression	855:865	arg1	measures					843:850	disease-specific measures	826:850	disease-specific measures of progression	826:865	FAC and FAP are pathologies that can be challenging to diagnose as there are no definitive biomarkers of disease; moreover, disease-specific measures of progression are lacking, and treatment options are limited.
28922609	9	69	theme	proteins	1774:1781	arg1	proteins					1774:1781	the serum proteins	1764:1781	the serum proteins	1764:1781	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	9	69	theme	proteins	1774:1781	arg1	192					1751:1753	192	1751:1753	192	1751:1753	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	9	70	theme	significant	1703:1713	arg1	differences					1729:1739	significant concentration differences	1703:1739	significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied	1703:1799	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	12	71	link	N-linked	2230:2237	arg1	glycosylation					2240:2252	glycosylation	2240:2252	glycosylation	2240:2252	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	9	72	dep	ATTRm	1656:1660	arg1	FAP					1671:1673	FAP	1671:1673	FAP	1671:1673	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	9	72	dep	ATTRm	1656:1660	arg1	FAC					1663:1665	FAC	1663:1665	FAC	1663:1665	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	3	73	theme	TTR	545:547	arg1	gene					549:552	the TTR gene	541:552	the TTR gene	541:552	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	7	74	theme	mass	1315:1318	arg1	technique					1354:1362	a powerful technique	1343:1362	a powerful technique in profiling proteomes	1343:1385	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	74	theme	mass	1315:1318	arg1	MRM-MS					1334:1339	MRM-MS	1334:1339	MRM-MS	1334:1339	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	74	theme	mass	1315:1318	arg1	spectrometry					1320:1331	Multiple-reaction monitoring mass spectrometry	1286:1331	Multiple-reaction monitoring mass spectrometry (MRM-MS)	1286:1340	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	10	75	theme	TTR	1988:1990	arg1	levels					1978:1983	significantly lower levels	1958:1983	significantly lower levels of TTR	1958:1990	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	12	76	gly	glycoprotein	2255:2266	arg1	glycoprotein					2255:2266	glycoprotein	2255:2266	glycoprotein	2255:2266	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	7	77	theme	Multiple-reaction	1286:1302	arg1	technique					1354:1362	a powerful technique	1343:1362	a powerful technique in profiling proteomes	1343:1385	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	77	theme	Multiple-reaction	1286:1302	arg1	MRM-MS					1334:1339	MRM-MS	1334:1339	MRM-MS	1334:1339	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	77	theme	Multiple-reaction	1286:1302	arg1	spectrometry					1320:1331	Multiple-reaction monitoring mass spectrometry	1286:1331	Multiple-reaction monitoring mass spectrometry (MRM-MS)	1286:1340	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	10	78	theme	lower	1972:1976	arg1	levels					1978:1983	significantly lower levels	1958:1983	significantly lower levels of TTR	1958:1990	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	0	79	theme	Transthyretin	75:87	arg1	Amyloidosis					89:99	Familial Transthyretin Amyloidosis	66:99	Familial Transthyretin Amyloidosis (ATTRm)	66:107	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	0	79	theme	Transthyretin	75:87	arg1	ATTRm					102:106	ATTRm	102:106	ATTRm	102:106	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	14	80	theme	control	2561:2567	arg1	sera					2569:2572	ATTRm patient and control sera	2543:2572	sera	2569:2572	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	5	81	theme	progression	1064:1074	arg1	measurement					1041:1051	accurate measurement	1032:1051	accurate measurement of amyloid progression	1032:1074	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	5	81	theme	progression	1064:1074	arg1	response					1080:1087	response	1080:1087	response to treatment	1080:1100	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	1	82	theme	plasma	142:147	arg1	protein					161:167	a plasma circulating protein	140:167	normally a plasma circulating protein	131:167	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
28922609	1	82	theme	plasma	142:147	arg1	Transthyretin					110:122	Transthyretin	110:122	Transthyretin (TTR)	110:128	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
28922609	7	83	from	technique	1354:1362	arg1	proteomes					1377:1385	profiling proteomes	1367:1385	profiling proteomes	1367:1385	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	9	84	theme	Proteomic	1634:1642	arg1	analyses					1644:1651	Proteomic analyses	1634:1651	Proteomic analyses of ATTRm (FAC and FAP) and control samples	1634:1694	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	6	85	theme	ATTRm	1279:1283	arg1	FAC					1258:1260	FAC	1258:1260	FAC	1258:1260	In this study, the goal was to investigate serum proteomic features unique to FAC and FAP types of ATTRm.
28922609	6	85	theme	ATTRm	1279:1283	arg1	types					1270:1274	FAP types	1266:1274	FAP types	1266:1274	In this study, the goal was to investigate serum proteomic features unique to FAC and FAP types of ATTRm.
28922609	5	86	theme	accurate	1032:1039	arg1	measurement					1041:1051	accurate measurement	1032:1051	accurate measurement of amyloid progression	1032:1074	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	11	87	theme	functional	2040:2049	arg1	clustering					2051:2060	Annotated functional clustering	2030:2060	Annotated functional clustering	2030:2060	Annotated functional clustering identified extracellular region, signal, and signal peptide as terms common to FAC and FAP.
28922609	9	88	theme	ATTRm	1656:1660	arg1	analyses					1644:1651	Proteomic analyses	1634:1651	Proteomic analyses of ATTRm (FAC and FAP) and control samples	1634:1694	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	0	89	theme	Proteomic	6:14	arg1	Variability					16:26	Serum Proteomic Variability	0:26	Serum Proteomic Variability	0:26	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	12	90	dep	site	2224:2227	arg1	glycosylation					2210:2222	secreted, glycosylation site	2200:2227	glycosylation	2210:2222	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	14	91	theme	ATTRm	2543:2547	arg1	patient					2549:2555	ATTRm patient and control sera	2543:2572	patient	2549:2555	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	5	92	theme	key	1114:1116	arg1	information					1118:1128	key information	1114:1128	key information regarding FAC and FAP pathobiological mechanisms	1114:1177	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	10	93	from	differences	1827:1837	arg1	concentrations					1842:1855	concentrations	1842:1855	concentrations as well as interactions and functions of several proteins	1842:1913	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	10	93	from	differences	1827:1837	arg1	interactions					1868:1879	interactions	1868:1879	interactions	1868:1879	In comparing FAC to FAP, differences in concentrations as well as interactions and functions of several proteins were identified as unique to each disease; significantly lower levels of TTR were specific to FAC, but not to FAP.
28922609	15	94	contain	have	2748:2751	arg1	identification					2689:2702	The identification	2685:2702	The identification of serum proteins unique to FAC and FAP	2685:2742	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	15	94	contain	have	2748:2751	arg2	utility					2779:2785	diagnostic and prognostic utility	2753:2785	diagnostic and prognostic utility	2753:2785	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	14	95	from	differences	2523:2533	arg1	levels					2643:2648	the circulating levels	2627:2648	the circulating levels of several proteins including TTR	2627:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	0	96	theme	Clinical	44:51	arg1	Phenotype					53:61	Clinical Phenotype	44:61	Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm)	44:107	Serum Proteomic Variability Associated with Clinical Phenotype in Familial Transthyretin Amyloidosis (ATTRm).
28922609	7	97	from	patients	1477:1484	arg1	samples					1452:1458	samples	1452:1458	samples from FAC and FAP patients	1452:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	97	from	patients	1477:1484	arg1	concentrations					1418:1431	the serum concentrations	1408:1431	the serum concentrations of 160 proteins in samples from FAC and FAP patients	1408:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	98	theme	FAC	1465:1467	arg1	patients					1477:1484	FAC and FAP patients	1465:1484	patients	1477:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	14	99	theme	significant	2501:2511	arg1	differences					2523:2533	significant proteomic differences	2501:2533	significant proteomic differences between ATTRm patient and control sera	2501:2572	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	9	100	theme	control	1680:1686	arg1	samples					1688:1694	control samples	1680:1694	control samples	1680:1694	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	12	101	theme	secreted	2200:2207	arg1	site					2224:2227	secreted, glycosylation site	2200:2227	site	2224:2227	Conversely, disulfide bond was unique to FAC; secreted, glycosylation site: N-linked, glycosylation, glycoprotein, polymorphism, and sequence variant were associated solely with FAP.
28922609	3	102	theme	familial	587:594	arg1	cardiomyopathy					604:617	familial amyloid cardiomyopathy	587:617	familial amyloid cardiomyopathy (FAC)	587:623	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	102	theme	familial	587:594	arg1	ATTR					445:448	ATTR	445:448	ATTR	445:448	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	102	theme	familial	587:594	arg1	FAC					620:622	FAC	620:622	FAC	620:622	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	2	103	theme	diseases	381:388	arg1	group					372:376	this group	367:376	this group of diseases	367:388	Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated.
28922609	2	103	theme	diseases	381:388	arg1	diseases					381:388	diseases	381:388	diseases	381:388	Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated.
28922609	1	104	theme	nerve	302:306	arg1	tissues					308:314	nerve tissues	302:314	nerve tissues	302:314	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
28922609	5	105	theme	indicators	961:970	arg1	discovery					925:933	the discovery	921:933	the discovery of sensitive and specific indicators of disease	921:981	Thus, the discovery of sensitive and specific indicators of disease has the potential to improve recognition, enable accurate measurement of amyloid progression and response to treatment, and reveal key information regarding FAC and FAP pathobiological mechanisms.
28922609	3	106	theme	variant	477:483	arg1	proteins					489:496	amyloid-forming variant TTR proteins	461:496	amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene	461:552	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	3	106	theme	variant	477:483	arg1	ATTRm					499:503	ATTRm	499:503	ATTRm	499:503	ATTR, caused by amyloid-forming variant TTR proteins (ATTRm) that arise from point mutations in the TTR gene, were classically referred to as familial amyloid cardiomyopathy (FAC) or familial amyloid polyneuropathy (FAP), reflecting the clinical phenotype.
28922609	7	107	theme	proteins	1440:1447	arg1	concentrations					1418:1431	the serum concentrations	1408:1431	the serum concentrations of 160 proteins in samples from FAC and FAP patients	1408:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	14	108	theme	ATTRm	2586:2590	arg1	variations					2613:2622	ATTRm phenotype-associated variations	2586:2622	ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR	2586:2682	This study demonstrates significant proteomic differences between ATTRm patient and control sera, as well as ATTRm phenotype-associated variations in the circulating levels of several proteins including TTR.
28922609	9	109	theme	concentration	1715:1727	arg1	differences					1729:1739	significant concentration differences	1703:1739	significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied	1703:1799	Proteomic analyses of ATTRm (FAC and FAP) and control samples showed significant concentration differences in 107 of 192 (56%) of the serum proteins that were studied.
28922609	7	110	from	concentrations	1418:1431	arg1	patients					1477:1484	FAC and FAP patients	1465:1484	patients	1477:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	7	110	from	concentrations	1418:1431	arg1	samples					1452:1458	samples	1452:1458	samples from FAC and FAP patients	1452:1484	Multiple-reaction monitoring mass spectrometry (MRM-MS), a powerful technique in profiling proteomes, was used to measure the serum concentrations of 160 proteins in samples from FAC and FAP patients.
28922609	15	111	theme	disease	2836:2842	arg1	mechanisms					2844:2853	disease mechanisms	2836:2853	disease mechanisms	2836:2853	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	15	112	theme	important	2814:2822	arg1	clues					2824:2828	important clues	2814:2828	important clues about disease mechanisms	2814:2853	The identification of serum proteins unique to FAC and FAP may have diagnostic and prognostic utility and could possibly provide important clues about disease mechanisms.
28922609	8	113	theme	control	1530:1536	arg1	sera					1538:1541	healthy control sera	1522:1541	healthy control sera obtained from individuals matched to age (≥60 years), gender (male), and race (Caucasian)	1522:1631	Results were compared to data from healthy control sera obtained from individuals matched to age (≥60 years), gender (male), and race (Caucasian).
28922609	1	114	theme	extracellular	229:241	arg1	deposition					243:252	extracellular deposition	229:252	extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues	229:314	Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues.
29708975	9	0	from	report	1213:1218	arg1	epidemiology					1237:1248	the molecular epidemiology	1223:1248	the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1223:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	6	1	theme	infections	785:794	arg1	majority					773:780	majority	773:780	majority of infections in children less than 06 months	773:826	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	7	2	theme	Pakistani	854:862	arg1	strains					867:873	Pakistani G3 strains	854:873	Pakistani G3 strains	854:873	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	9	3	theme	RV	1343:1344	arg1	vaccine					1346:1352	RV vaccine	1343:1352	RV vaccine	1343:1352	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	5	4	dep	responsible	607:617	arg1	gastroenteritis					623:637	RVA gastroenteritis	619:637	RVA gastroenteritis	619:637	We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014.
29708975	0	5	from	prevalence	5:14	arg1	children					48:55	hospitalized children	35:55	hospitalized children in Rawalpindi, Pakistan during 2014	35:91	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.
29708975	9	6	theme	strains	1266:1272	arg1	epidemiology					1237:1248	the molecular epidemiology	1223:1248	the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1223:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	7	7	theme	Phylogenetic	829:840	arg1	analysis					842:849	Phylogenetic analysis	829:849	Phylogenetic analysis of Pakistani G3 strains	829:873	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	1	8	theme	leading	127:133	arg1	cause					135:139	the leading cause	123:139	the leading cause of severe diarrhea among children in both developed and developing countries	123:216	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	1	8	theme	leading	127:133	arg1	species					106:112	Rotavirus A species	94:112	Rotavirus A species (RVA)	94:118	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	7	9	theme	new	913:915	arg1	"					927:927	"new variant G3"	912:927	"new variant G3"	912:927	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	8	10	link	N-linked	1109:1116	arg1	site					1132:1135	an extra N-linked glycosylation site	1100:1135	an extra N-linked glycosylation site	1100:1135	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	8	11	gly	glycosylation	1118:1130	arg2	site					1132:1135	an extra N-linked glycosylation site	1100:1135	an extra N-linked glycosylation site	1100:1135	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	8	12	theme	RotaTeqTM	1166:1174	arg1	strain					1156:1161	the G3 strain	1149:1161	the G3 strain of RotaTeqTM	1149:1174	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	9	13	theme	country	1397:1403	arg1	program					1382:1388	the routine immunization program	1357:1388	the routine immunization program of the country on priority	1357:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	9	14	theme	molecular	1227:1235	arg1	epidemiology					1237:1248	the molecular epidemiology	1223:1248	the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1223:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	0	15	from	children	48:55	arg1	Pakistan					72:79	Pakistan	72:79	Pakistan	72:79	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.
29708975	8	16	contain	containing	1089:1098	arg1	3d					1085:1086	sub-lineage 3d	1073:1086	sub-lineage 3d	1073:1086	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	8	16	contain	containing	1089:1098	arg2	site					1132:1135	an extra N-linked glycosylation site	1100:1135	an extra N-linked glycosylation site	1100:1135	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	9	17	theme	first	1207:1211	arg1	report					1213:1218	the first report	1203:1218	the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1203:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	9	17	theme	first	1207:1211	arg1	this					1195:1198	this	1195:1198	this	1195:1198	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	8	18	theme	glycosylation	1118:1130	arg1	site					1132:1135	an extra N-linked glycosylation site	1100:1135	an extra N-linked glycosylation site	1100:1135	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	9	19	theme	routine	1361:1367	arg1	program					1382:1388	the routine immunization program	1357:1388	the routine immunization program of the country on priority	1357:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	9	20	theme	rotavirus	1256:1264	arg1	strains					1266:1272	G3 rotavirus strains	1253:1272	G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1253:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	9	21	theme	immunization	1369:1380	arg1	program					1382:1388	the routine immunization program	1357:1388	the routine immunization program of the country on priority	1357:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	6	22	theme	common	749:754	arg1	genotype					756:763	the most common genotype	740:763	the most common genotype causing majority of infections in children less than 06 months	740:826	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	6	22	theme	common	749:754	arg1	G3P[8					701:705	G3P[8	701:705	G3P[8	701:705	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	9	23	from	Pakistan	1279:1286	arg1	strains					1266:1272	G3 rotavirus strains	1253:1272	G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1253:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	9	23	from	Pakistan	1279:1286	arg1	epidemiology					1237:1248	the molecular epidemiology	1223:1248	the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1223:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	2	24	theme	G	239:239	arg1	types					241:245	different RVA G types	225:245	different RVA G types	225:245	Among different RVA G types, humans are most commonly infected with G1, G2, G3, G4 and G9.
29708975	3	25	theme	new	352:354	arg1	"					366:366	"new variant G3"	351:366	"new variant G3"	351:366	During 2003-2004, G3 rotavirus termed as "new variant G3" emerged in Japan that later disseminated to multiple countries across the world.
29708975	9	26	from	epidemiology	1237:1248	arg1	Pakistan					1279:1286	Pakistan	1279:1286	Pakistan	1279:1286	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	9	26	from	epidemiology	1237:1248	arg1	calls					1292:1296	calls	1292:1296	calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1292:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	6	27	from	infections	785:794	arg1	children					799:806	children	799:806	children less than 06 months	799:826	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	7	28	theme	G3	933:934	arg1	strains					936:942	G3 strains	933:942	G3 strains	933:942	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	6	29	dep	=	718:718	arg1	%					713:713	18.3%	709:713	18.3%	709:713	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	6	30	dep	G3P[8	701:705	arg1	=					718:718	=	718:718	=	718:718	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	1	31	theme	severe	144:149	arg1	diarrhea					151:158	severe diarrhea	144:158	severe diarrhea	144:158	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	0	32	theme	High	0:3	arg1	prevalence					5:14	High prevalence	0:14	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.	0:92	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.
29708975	4	33	theme	G3	458:459	arg1	rotaviruses					461:471	G3 rotaviruses	458:471	G3 rotaviruses	458:471	Although G3 rotaviruses are now commonly detected globally, they have been rarely reported from Pakistan.
29708975	1	34	theme	diarrhea	151:158	arg1	cause					135:139	the leading cause	123:139	the leading cause of severe diarrhea among children in both developed and developing countries	123:216	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	1	34	theme	diarrhea	151:158	arg1	species					106:112	Rotavirus A species	94:112	Rotavirus A species (RVA)	94:118	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	0	35	theme	G3	19:20	arg1	rotavirus					22:30	G3 rotavirus	19:30	G3 rotavirus	19:30	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.
29708975	5	36	theme	strains	599:605	arg1	diversity					583:591	the genetic diversity	571:591	the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan	571:686	We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014.
29708975	8	37	theme	G3	1153:1154	arg1	strain					1156:1161	the G3 strain	1149:1161	the G3 strain of RotaTeqTM	1149:1174	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	8	38	theme	Pakistani	1023:1031	arg1	strains					1036:1042	Pakistani G3 strains	1023:1042	Pakistani G3 strains	1023:1042	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	7	39	theme	variant	917:923	arg1	"					927:927	"new variant G3"	912:927	"new variant G3"	912:927	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	5	40	theme	responsible	607:617	arg1	strains					599:605	G3 strains	596:605	G3 strains responsible RVA gastroenteritis	596:637	We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014.
29708975	9	41	from	calls	1292:1296	arg1	strains					1266:1272	G3 rotavirus strains	1253:1272	G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1253:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	9	41	from	calls	1292:1296	arg1	epidemiology					1237:1248	the molecular epidemiology	1223:1248	the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1223:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	1	42	theme	Rotavirus	94:102	arg1	cause					135:139	the leading cause	123:139	the leading cause of severe diarrhea among children in both developed and developing countries	123:216	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	1	42	theme	Rotavirus	94:102	arg1	RVA					115:117	RVA	115:117	RVA	115:117	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	1	42	theme	Rotavirus	94:102	arg1	species					106:112	Rotavirus A species	94:112	Rotavirus A species (RVA)	94:118	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	3	43	theme	G3	328:329	arg1	rotavirus					331:339	G3 rotavirus	328:339	G3 rotavirus termed as "new variant G3"	328:366	During 2003-2004, G3 rotavirus termed as "new variant G3" emerged in Japan that later disseminated to multiple countries across the world.
29708975	9	44	theme	immediate	1302:1310	arg1	measures					1321:1328	immediate response measures	1302:1328	immediate response measures	1302:1328	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	5	45	theme	RVA	619:621	arg1	gastroenteritis					623:637	RVA gastroenteritis	619:637	RVA gastroenteritis	619:637	We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014.
29708975	8	46	theme	extra	1103:1107	arg1	site					1132:1135	an extra N-linked glycosylation site	1100:1135	an extra N-linked glycosylation site	1100:1135	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	8	47	theme	sub-lineage	1073:1083	arg1	3d					1085:1086	sub-lineage 3d	1073:1086	sub-lineage 3d	1073:1086	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	3	48	theme	variant	356:362	arg1	"					366:366	"new variant G3"	351:366	"new variant G3"	351:366	During 2003-2004, G3 rotavirus termed as "new variant G3" emerged in Japan that later disseminated to multiple countries across the world.
29708975	0	49	theme	rotavirus	22:30	arg1	prevalence					5:14	High prevalence	0:14	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.	0:92	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.
29708975	6	50	theme	06	818:819	arg1	months					821:826	06 months	818:826	06 months	818:826	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	7	51	theme	G3	925:926	arg1	"					927:927	"new variant G3"	912:927	"new variant G3"	912:927	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	8	52	theme	G3	1033:1034	arg1	strains					1036:1042	Pakistani G3 strains	1023:1042	Pakistani G3 strains	1023:1042	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	7	53	theme	amino	887:891	arg1	similarity					898:907	high amino acid similarity	882:907	high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary	882:1003	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	3	54	theme	G3	364:365	arg1	"					366:366	"new variant G3"	351:366	"new variant G3"	351:366	During 2003-2004, G3 rotavirus termed as "new variant G3" emerged in Japan that later disseminated to multiple countries across the world.
29708975	5	55	theme	genetic	575:581	arg1	diversity					583:591	the genetic diversity	571:591	the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan	571:686	We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014.
29708975	7	56	theme	acid	893:896	arg1	similarity					898:907	high amino acid similarity	882:907	high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary	882:1003	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	1	57	theme	A	104:104	arg1	cause					135:139	the leading cause	123:139	the leading cause of severe diarrhea among children in both developed and developing countries	123:216	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	1	57	theme	A	104:104	arg1	RVA					115:117	RVA	115:117	RVA	115:117	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	1	57	theme	A	104:104	arg1	species					106:112	Rotavirus A species	94:112	Rotavirus A species (RVA)	94:118	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	0	58	theme	hospitalized	35:46	arg1	children					48:55	hospitalized children	35:55	hospitalized children in Rawalpindi, Pakistan during 2014	35:91	High prevalence of G3 rotavirus in hospitalized children in Rawalpindi, Pakistan during 2014.
29708975	6	59	theme	less	808:811	arg1	children					799:806	children	799:806	children less than 06 months	799:826	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	6	60	from	children	799:806	arg1	majority					773:780	majority	773:780	majority of infections in children less than 06 months	773:826	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	8	61	theme	N-linked	1109:1116	arg1	site					1132:1135	an extra N-linked glycosylation site	1100:1135	an extra N-linked glycosylation site	1100:1135	Pakistani G3 strains belonged to lineage 3 within sub-lineage 3d, containing an extra N-linked glycosylation site compared to the G3 strain of RotaTeqTM.
29708975	2	62	theme	RVA	235:237	arg1	types					241:245	different RVA G types	225:245	different RVA G types	225:245	Among different RVA G types, humans are most commonly infected with G1, G2, G3, G4 and G9.
29708975	1	63	from	children	166:173	arg1	developed					183:191	developed	183:191	developed	183:191	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	1	63	from	children	166:173	arg1	countries					208:216	developing countries	197:216	developing countries	197:216	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	9	64	theme	response	1312:1319	arg1	measures					1321:1328	immediate response measures	1302:1328	immediate response measures	1302:1328	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	5	65	theme	G3	596:597	arg1	strains					599:605	G3 strains	596:605	G3 strains responsible RVA gastroenteritis	596:637	We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014.
29708975	2	66	theme	different	225:233	arg1	types					241:245	different RVA G types	225:245	different RVA G types	225:245	Among different RVA G types, humans are most commonly infected with G1, G2, G3, G4 and G9.
29708975	7	67	theme	G3	864:865	arg1	strains					867:873	Pakistani G3 strains	854:873	Pakistani G3 strains	854:873	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	9	68	from	program	1382:1388	arg1	priority					1408:1415	priority	1408:1415	priority	1408:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	7	69	theme	high	882:885	arg1	similarity					898:907	high amino acid similarity	882:907	high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary	882:1003	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	7	70	theme	strains	867:873	arg1	analysis					842:849	Phylogenetic analysis	829:849	Phylogenetic analysis of Pakistani G3 strains	829:873	Phylogenetic analysis of Pakistani G3 strains showed high amino acid similarity to "new variant G3" and G3 strains reported from China, Russia, USA, Japan, Belgium and Hungary during 2007-2012.
29708975	3	71	theme	multiple	412:419	arg1	countries					421:429	multiple countries	412:429	multiple countries across the world	412:446	During 2003-2004, G3 rotavirus termed as "new variant G3" emerged in Japan that later disseminated to multiple countries across the world.
29708975	9	72	theme	G3	1253:1254	arg1	rotavirus					1256:1264	G3 rotavirus	1253:1264	G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority	1253:1415	To our knowledge, this is the first report on the molecular epidemiology of G3 rotavirus strains from Pakistan and calls for immediate response measures to introduce RV vaccine in the routine immunization program of the country on priority.
29708975	1	73	theme	developing	197:206	arg1	countries					208:216	developing countries	197:216	developing countries	197:216	Rotavirus A species (RVA) is the leading cause of severe diarrhea among children in both developed and developing countries.
29708975	6	74	from	majority	773:780	arg1	children					799:806	children	799:806	children less than 06 months	799:826	G3P[8] (18.3%; n = 24) was detected as the most common genotype causing majority of infections in children less than 06 months.
29708975	5	75	from	diversity	583:591	arg1	children					642:649	children	642:649	children hospitalized in Rawalpindi, Pakistan	642:686	We investigated the genetic diversity of G3 strains responsible RVA gastroenteritis in children hospitalized in Rawalpindi, Pakistan during 2014.
29780502	2	0	from	glycans	205:211	arg1	particular					216:225	particular	216:225	particular	216:225	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	4	1	theme	galactose	866:874	arg1	moieties					876:883	α-O-linked mannose, glucose, and galactose moieties	833:883	α-O-linked mannose, glucose, and galactose moieties	833:883	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	6	2	theme	linker	1295:1300	arg1	features					1279:1286	the conformational features	1260:1286	the conformational features of the linker	1260:1300	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	3	3	theme	preferred	525:533	arg1	glycan					535:540	the preferred glycan	521:540	the preferred glycan	521:540	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	3	3	theme	preferred	525:533	arg1	mannose					504:510	mannose	504:510	mannose	504:510	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	2	4	from	O-mannosylation	342:356	arg1	regions					386:392	intrinsically disordered regions	361:392	intrinsically disordered regions	361:392	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	6	5	theme	conformational	1264:1277	arg1	features					1279:1286	the conformational features	1260:1286	the conformational features of the linker	1260:1300	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	2	6	theme	secreted	283:290	arg1	proteins					292:299	secreted proteins	283:299	secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions	283:462	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	7	7	theme	backbone	1486:1493	arg1	orientation					1495:1505	perpendicular glycan-protein backbone orientation	1457:1505	perpendicular glycan-protein backbone orientation	1457:1505	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	6	8	theme	C2-hydroxyl	1166:1176	arg1	2-OH					1185:1188	2-OH	1185:1188	2-OH	1185:1188	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	6	8	theme	C2-hydroxyl	1166:1176	arg1	group					1178:1182	the C2-hydroxyl group	1162:1182	the C2-hydroxyl group (2-OH)	1162:1189	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	8	9	from	interactions	1626:1637	arg1	contributions					1592:1604	contributions	1592:1604	contributions from protein-glycan interactions, protein flexibility, and protein stability	1592:1681	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	3	10	theme	protein	582:588	arg1	sequence					590:597	the neighboring protein sequence	566:597	the neighboring protein sequence	566:597	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	9	11	theme	driving	1757:1763	arg1	resistance					1715:1724	resistance	1715:1724	resistance to proteolysis	1715:1739	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	9	11	theme	driving	1757:1763	arg1	force					1765:1769	an important driving force	1744:1769	an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs	1744:1828	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	7	12	theme	equatorial	1402:1411	arg1	groups					1418:1423	equatorial 2-OH groups	1402:1423	equatorial 2-OH groups	1402:1423	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	6	13	theme	glycan-peptide	1220:1233	arg1	bond					1235:1238	the glycan-peptide bond	1216:1238	the glycan-peptide bond	1216:1238	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	4	14	theme	non-glycosylated	899:914	arg1	linker					916:921	a non-glycosylated linker	897:921	a non-glycosylated linker	897:921	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	1	15	theme	diverse	115:121	arg1	modification					142:153	a diverse post-translational modification	113:153	a diverse post-translational modification that serves myriad biological functions	113:193	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	1	15	theme	diverse	115:121	arg1	glycosylation					96:108	Protein glycosylation	88:108	Protein glycosylation	88:108	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	9	16	theme	α-mannose	1801:1809	arg1	selection					1788:1796	evolutionary selection	1775:1796	evolutionary selection of α-mannose in eukaryotic IDPs	1775:1828	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	7	17	theme	chain	1366:1370	arg1	torsions					1341:1348	the torsions	1337:1348	the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation	1337:1505	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	2	18	from	fungi	306:310	arg1	proteins					292:299	secreted proteins	283:299	secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions	283:462	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	9	19	theme	eukaryotic	1814:1823	arg1	IDPs					1825:1828	eukaryotic IDPs	1814:1828	eukaryotic IDPs	1814:1828	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	7	20	theme	IDP	1357:1359	arg1	chain					1366:1370	the IDP main chain	1353:1370	the IDP main chain	1353:1370	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	2	21	from	yeast	316:320	arg1	proteins					292:299	secreted proteins	283:299	secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions	283:462	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	0	22	theme	disordered	67:76	arg1	proteins					78:85	intrinsically disordered proteins	53:85	intrinsically disordered proteins	53:85	The impact of O-glycan chemistry on the stability of intrinsically disordered proteins.
29780502	1	23	theme	biological	174:183	arg1	functions					185:193	myriad biological functions	167:193	myriad biological functions	167:193	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	6	24	theme	adjacent	1204:1211	arg1	α-mannose					1194:1202	α-mannose	1194:1202	α-mannose adjacent to the glycan-peptide bond	1194:1238	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	4	25	theme	O-mannosylated	784:797	arg1	IDP					755:757	a model IDP	747:757	a model IDP	747:757	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	4	25	theme	O-mannosylated	784:797	arg1	linker					799:804	a natively O-mannosylated linker	773:804	a natively O-mannosylated linker from a fungal enzyme	773:825	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	6	26	theme	molecular	1073:1081	arg1	simulations					1092:1102	extensive molecular dynamics simulations	1063:1102	extensive molecular dynamics simulations	1063:1102	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	9	27	theme	glycan	1854:1859	arg1	motifs					1861:1866	glycan motifs	1854:1866	glycan motifs for proteolysis protection	1854:1893	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	4	28	theme	model	749:753	arg1	IDP					755:757	a model IDP	747:757	a model IDP	747:757	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	4	28	theme	model	749:753	arg1	linker					799:804	a natively O-mannosylated linker	773:804	a natively O-mannosylated linker from a fungal enzyme	773:825	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	1	29	theme	Protein	88:94	arg1	modification					142:153	a diverse post-translational modification	113:153	a diverse post-translational modification that serves myriad biological functions	113:193	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	1	29	theme	Protein	88:94	arg1	glycosylation					96:108	Protein glycosylation	88:108	Protein glycosylation	88:108	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	6	30	theme	α-mannose	1194:1202	arg1	configuration					1145:1157	the axial configuration	1135:1157	the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond	1135:1238	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	2	31	theme	O-linked	196:203	arg1	glycans					205:211	O-linked glycans	196:211	O-linked glycans in particular	196:225	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	0	32	theme	chemistry	23:31	arg1	impact					4:9	The impact	0:9	The impact of O-glycan chemistry on the stability of intrinsically disordered proteins	0:85	The impact of O-glycan chemistry on the stability of intrinsically disordered proteins.
29780502	5	33	theme	proteolysis	1010:1020	arg1	protection					1022:1031	proteolysis protection	1010:1031	proteolysis protection	1010:1031	Upon exposure to thermolysin, O-mannosylation, by far, provides the highest extent of proteolysis protection.
29780502	4	34	theme	α-O-linked	833:842	arg1	moieties					876:883	α-O-linked mannose, glucose, and galactose moieties	833:883	α-O-linked mannose, glucose, and galactose moieties	833:883	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	2	35	theme	disordered	375:384	arg1	regions					386:392	intrinsically disordered regions	361:392	intrinsically disordered regions	361:392	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	8	36	theme	protein	1640:1646	arg1	flexibility					1648:1658	protein flexibility	1640:1658	protein flexibility	1640:1658	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	2	37	gly	O-mannosylation	342:356	arg1	regions					386:392	intrinsically disordered regions	361:392	intrinsically disordered regions	361:392	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	9	38	attach	attach	1951:1956	arg1	sequence					1928:1935	the protein sequence	1916:1935	the protein sequence to which they attach	1916:1956	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	9	38	attach	attach	1951:1956	arg2	they					1946:1949	they	1946:1949	they	1946:1949	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	4	39	theme	fungal	813:818	arg1	enzyme					820:825	a fungal enzyme	811:825	a fungal enzyme	811:825	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	8	40	theme	protein	1665:1671	arg1	stability					1673:1681	protein stability	1665:1681	protein stability	1665:1681	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	3	41	gly	glycosylated	659:670	arg1	proteins					697:704	glycosylated intrinsically disordered proteins	659:704	glycosylated intrinsically disordered proteins (IDPs)	659:711	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	3	41	gly	glycosylated	659:670	arg1	IDPs					707:710	IDPs	707:710	IDPs	707:710	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	3	42	from	proteolysis	644:654	arg1	proteins					697:704	glycosylated intrinsically disordered proteins	659:704	glycosylated intrinsically disordered proteins (IDPs)	659:711	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	3	42	from	proteolysis	644:654	arg1	IDPs					707:710	IDPs	707:710	IDPs	707:710	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	7	43	theme	perpendicular	1457:1469	arg1	orientation					1495:1505	perpendicular glycan-protein backbone orientation	1457:1505	perpendicular glycan-protein backbone orientation	1457:1505	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	8	44	from	flexibility	1648:1658	arg1	contributions					1592:1604	contributions	1592:1604	contributions from protein-glycan interactions, protein flexibility, and protein stability	1592:1681	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	7	45	theme	glycan-protein	1471:1484	arg1	orientation					1495:1505	perpendicular glycan-protein backbone orientation	1457:1505	perpendicular glycan-protein backbone orientation	1457:1505	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	4	46	theme	mannose	844:850	arg1	moieties					876:883	α-O-linked mannose, glucose, and galactose moieties	833:883	α-O-linked mannose, glucose, and galactose moieties	833:883	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	6	47	theme	group	1178:1182	arg1	configuration					1145:1157	the axial configuration	1135:1157	the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond	1135:1238	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	4	48	gly	O-mannosylated	784:797	arg1	IDP					755:757	a model IDP	747:757	a model IDP	747:757	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	4	48	gly	O-mannosylated	784:797	arg1	linker					799:804	a natively O-mannosylated linker	773:804	a natively O-mannosylated linker from a fungal enzyme	773:825	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	3	49	theme	neighboring	570:580	arg1	sequence					590:597	the neighboring protein sequence	566:597	the neighboring protein sequence	566:597	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	4	50	theme	glucose	853:859	arg1	moieties					876:883	α-O-linked mannose, glucose, and galactose moieties	833:883	α-O-linked mannose, glucose, and galactose moieties	833:883	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	8	51	from	stability	1673:1681	arg1	contributions					1592:1604	contributions	1592:1604	contributions from protein-glycan interactions, protein flexibility, and protein stability	1592:1681	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	4	52	gly	non-glycosylated	899:914	arg1	linker					916:921	a non-glycosylated linker	897:921	a non-glycosylated linker	897:921	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	9	53	theme	important	1747:1755	arg1	resistance					1715:1724	resistance	1715:1724	resistance to proteolysis	1715:1739	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	9	53	theme	important	1747:1755	arg1	force					1765:1769	an important driving force	1744:1769	an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs	1744:1828	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	2	54	with	eukaryotes	266:275	arg1	proteins					292:299	secreted proteins	283:299	secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions	283:462	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	9	55	theme	evolutionary	1775:1786	arg1	selection					1788:1796	evolutionary selection	1775:1796	evolutionary selection of α-mannose in eukaryotic IDPs	1775:1828	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	7	56	theme	other	1382:1386	arg1	glycans					1388:1394	other glycans	1382:1394	other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation	1382:1505	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	4	57	from	enzyme	820:825	arg1	IDP					755:757	a model IDP	747:757	a model IDP	747:757	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	4	57	from	enzyme	820:825	arg1	linker					799:804	a natively O-mannosylated linker	773:804	a natively O-mannosylated linker from a fungal enzyme	773:825	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	1	58	theme	post-translational	123:140	arg1	modification					142:153	a diverse post-translational modification	113:153	a diverse post-translational modification that serves myriad biological functions	113:193	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	1	58	theme	post-translational	123:140	arg1	glycosylation					96:108	Protein glycosylation	88:108	Protein glycosylation	88:108	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	8	59	theme	IDP	1524:1526	arg1	stiffening					1528:1537	IDP stiffening	1524:1537	IDP stiffening due to O-mannosylation	1524:1560	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	7	60	theme	more	1372:1375	arg1	torsions					1341:1348	the torsions	1337:1348	the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation	1337:1505	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	0	61	theme	intrinsically	53:65	arg1	proteins					78:85	intrinsically disordered proteins	53:85	intrinsically disordered proteins	53:85	The impact of O-glycan chemistry on the stability of intrinsically disordered proteins.
29780502	9	62	from	selection	1788:1796	arg1	IDPs					1825:1828	eukaryotic IDPs	1814:1828	eukaryotic IDPs	1814:1828	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	7	63	theme	main	1361:1364	arg1	chain					1366:1370	the IDP main chain	1353:1370	the IDP main chain	1353:1370	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	0	64	theme	proteins	78:85	arg1	stability					40:48	the stability	36:48	the stability of intrinsically disordered proteins	36:85	The impact of O-glycan chemistry on the stability of intrinsically disordered proteins.
29780502	1	65	theme	myriad	167:172	arg1	functions					185:193	myriad biological functions	167:193	myriad biological functions	167:193	Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.
29780502	0	66	from	impact	4:9	arg1	stability					40:48	the stability	36:48	the stability of intrinsically disordered proteins	36:85	The impact of O-glycan chemistry on the stability of intrinsically disordered proteins.
29780502	7	67	theme	2-OH	1413:1416	arg1	groups					1418:1423	equatorial 2-OH groups	1402:1423	equatorial 2-OH groups	1402:1423	Specifically, α-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation.
29780502	8	68	theme	protease	1570:1577	arg1	action					1579:1584	protease action	1570:1584	protease action	1570:1584	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	6	69	theme	dynamics	1083:1090	arg1	simulations					1092:1102	extensive molecular dynamics simulations	1063:1102	extensive molecular dynamics simulations	1063:1102	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	2	70	theme	proteolysis	418:428	arg1	protection					430:439	proteolysis protection	418:439	proteolysis protection	418:439	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	6	71	theme	extensive	1063:1071	arg1	simulations					1092:1102	extensive molecular dynamics simulations	1063:1102	extensive molecular dynamics simulations	1063:1102	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	2	72	link	O-linked	196:203	arg1	glycans					205:211	O-linked glycans	196:211	O-linked glycans in particular	196:225	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	0	73	theme	O-glycan	14:21	arg1	chemistry					23:31	O-glycan chemistry	14:31	O-glycan chemistry	14:31	The impact of O-glycan chemistry on the stability of intrinsically disordered proteins.
29780502	9	74	theme	proteolysis	1872:1882	arg1	protection					1884:1893	proteolysis protection	1872:1893	proteolysis protection	1872:1893	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	8	75	theme	protein-glycan	1611:1624	arg1	interactions					1626:1637	protein-glycan interactions	1611:1637	protein-glycan interactions	1611:1637	We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability.
29780502	3	76	theme	glycosylated	659:670	arg1	proteins					697:704	glycosylated intrinsically disordered proteins	659:704	glycosylated intrinsically disordered proteins (IDPs)	659:711	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	3	76	theme	glycosylated	659:670	arg1	IDPs					707:710	IDPs	707:710	IDPs	707:710	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	4	77	theme	IDP	755:757	arg1	variants					735:742	variants	735:742	variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme	735:825	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	2	78	theme	other	448:452	arg1	functions					454:462	other functions	448:462	other functions	448:462	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
29780502	4	79	link	α-O-linked	833:842	arg1	moieties					876:883	α-O-linked mannose, glucose, and galactose moieties	833:883	α-O-linked mannose, glucose, and galactose moieties	833:883	Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with α-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker.
29780502	5	80	theme	protection	1022:1031	arg1	extent					1000:1005	the highest extent	988:1005	the highest extent of proteolysis protection	988:1031	Upon exposure to thermolysin, O-mannosylation, by far, provides the highest extent of proteolysis protection.
29780502	6	81	theme	axial	1139:1143	arg1	configuration					1145:1157	the axial configuration	1135:1157	the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond	1135:1238	To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of α-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker.
29780502	9	82	theme	protein	1920:1926	arg1	sequence					1928:1935	the protein sequence	1916:1935	the protein sequence to which they attach	1916:1956	Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of α-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.
29780502	3	83	theme	disordered	686:695	arg1	proteins					697:704	glycosylated intrinsically disordered proteins	659:704	glycosylated intrinsically disordered proteins (IDPs)	659:711	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	3	83	theme	disordered	686:695	arg1	IDPs					707:710	IDPs	707:710	IDPs	707:710	However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs).
29780502	5	84	theme	highest	992:998	arg1	extent					1000:1005	the highest extent	988:1005	the highest extent of proteolysis protection	988:1031	Upon exposure to thermolysin, O-mannosylation, by far, provides the highest extent of proteolysis protection.
29780502	2	85	theme	proteins	397:404	arg1	regions					386:392	intrinsically disordered regions	361:392	intrinsically disordered regions	361:392	O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions.
31516400	7	0	theme	body	1388:1391	arg1	fluids					1393:1398	body fluids	1388:1398	body fluids	1388:1398	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	1	theme	representing > 14,000	1240:1260	arg1	peptides					1230:1237	more than 30,000 glycosite-containing peptides	1192:1237	more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1192:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	1	theme	representing > 14,000	1240:1260	arg1	sites					1278:1282	representing > 14,000 N-glycosylation sites	1240:1282	representing > 14,000 N-glycosylation sites	1240:1282	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	2	2	theme	structure	426:434	arg1	interdependence					394:408	the interdependence	390:408	the interdependence of glycoprotein structure and protein function	390:455	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	5	3	used	used	931:934	arg2	resource					874:881	A database resource	863:881	A database resource termed N-GlycositeAtlas	863:905	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	1	4	theme	proteins	192:199	arg1	glycoprotein					146:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	1	4	theme	proteins	192:199	arg1	class					183:187	a highly interesting class	162:187	a highly interesting class of proteins for clinical and biological research	162:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	3	5	from	integration	550:560	arg1	tissues					600:606	different tissues	590:606	different tissues	590:606	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	3	5	from	integration	550:560	arg1	fluids					614:619	body fluids	609:619	body fluids	609:619	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	3	5	from	integration	550:560	arg1	types					629:633	cell types	624:633	cell types	624:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	7	6	link	human-derived	1365:1377	arg1	tissues					1379:1385	human-derived tissues	1365:1385	human-derived tissues	1365:1385	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	1	7	theme	clinical	205:212	arg1	research					229:236	clinical and biological research	205:236	clinical and biological research	205:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	4	8	theme	glycosite-containing	682:701	arg1	peptides					703:710	the human glycosite-containing peptides	672:710	the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory	672:860	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	2	9	gly	glycoproteins	284:296	arg1	glycoproteins					284:296	N-linked glycoproteins	275:296	N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics	275:352	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	3	10	theme	cell	624:627	arg1	types					629:633	cell types	624:633	cell types	624:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	1	11	theme	biological	218:227	arg1	research					229:236	clinical and biological research	205:236	clinical and biological research	205:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	6	12	theme	web	1048:1050	arg1	interface					1052:1060	a web interface	1046:1060	a web interface of N-GlycositeAtlas	1046:1080	Finally, a web interface of N-GlycositeAtlas was created to maximize the utility and value of the database.
31516400	1	13	gly	glycoprotein	146:157	arg1	glycoprotein					146:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	1	13	gly	glycoprotein	146:157	arg1	class					183:187	a highly interesting class	162:187	a highly interesting class of proteins for clinical and biological research	162:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	5	14	theme	distribution	944:955	arg1	analyses					957:964	the distribution analyses	940:964	the distribution analyses of glycoproteins among different human cells, tissues and body fluids	940:1034	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	7	15	from	sources	1347:1353	arg1	peptides					1230:1237	more than 30,000 glycosite-containing peptides	1192:1237	more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1192:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	15	from	sources	1347:1353	arg1	sites					1278:1282	representing > 14,000 N-glycosylation sites	1240:1282	representing > 14,000 N-glycosylation sites	1240:1282	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	16	theme	glycosite-containing	1209:1228	arg1	peptides					1230:1237	more than 30,000 glycosite-containing peptides	1192:1237	more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1192:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	16	theme	glycosite-containing	1209:1228	arg1	sites					1278:1282	representing > 14,000 N-glycosylation sites	1240:1282	representing > 14,000 N-glycosylation sites	1240:1282	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	17	contain	contains	1183:1190	arg2	peptides					1230:1237	more than 30,000 glycosite-containing peptides	1192:1237	more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1192:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	17	contain	contains	1183:1190	arg2	sites					1278:1282	representing > 14,000 N-glycosylation sites	1240:1282	representing > 14,000 N-glycosylation sites	1240:1282	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	17	contain	contains	1183:1190	arg1	database					1174:1181	The N-GlycositeAtlas database	1153:1181	The N-GlycositeAtlas database	1153:1181	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	8	18	theme	human	1461:1465	arg1	database					1483:1490	The entire human N-glycoproteome database	1450:1490	The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids	1450:1568	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	0	19	theme	human	66:70	arg1	glycoprotein					81:92	mass spectrometry-based human N-linked glycoprotein	42:92	mass spectrometry-based human N-linked glycoprotein	42:92	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	2	20	theme	N-linked	275:282	arg1	glycoproteins					284:296	N-linked glycoproteins	275:296	N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics	275:352	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	5	21	theme	human	999:1003	arg1	cells					1005:1009	different human cells	989:1009	different human cells	989:1009	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	7	22	theme	human-derived	1365:1377	arg1	tissues					1379:1385	human-derived tissues	1365:1385	human-derived tissues	1365:1385	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	3	23	from	fluids	614:619	arg1	integration					550:560	the integration	546:560	the integration of glycoproteomic data from different tissues, body fluids or cell types	546:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	3	23	from	fluids	614:619	arg1	data					580:583	glycoproteomic data	565:583	glycoproteomic data from different tissues, body fluids or cell types	565:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	0	24	theme	glycosylation	98:110	arg1	mapping					117:123	glycosylation site mapping	98:123	glycosylation site mapping	98:123	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	7	25	theme	different	1326:1334	arg1	sources					1347:1353	different biological sources	1326:1353	different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1326:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	25	theme	different	1326:1334	arg1	tissues					1379:1385	human-derived tissues	1365:1385	human-derived tissues	1365:1385	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	25	theme	different	1326:1334	arg1	fluids					1393:1398	body fluids	1388:1398	body fluids	1388:1398	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	25	theme	different	1326:1334	arg1	lines					1409:1413	cell lines	1404:1413	cell lines	1404:1413	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	26	from	N-glycoproteins	1305:1319	arg1	peptides					1230:1237	more than 30,000 glycosite-containing peptides	1192:1237	more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1192:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	26	from	N-glycoproteins	1305:1319	arg1	sites					1278:1282	representing > 14,000 N-glycosylation sites	1240:1282	representing > 14,000 N-glycosylation sites	1240:1282	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	8	27	theme	individual	1536:1545	arg1	tissues					1547:1553	individual tissues	1536:1553	individual tissues	1536:1553	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	6	28	theme	database	1135:1142	arg1	utility					1110:1116	utility	1110:1116	utility	1110:1116	Finally, a web interface of N-GlycositeAtlas was created to maximize the utility and value of the database.
31516400	6	28	theme	database	1135:1142	arg1	value					1122:1126	value	1122:1126	value	1122:1126	Finally, a web interface of N-GlycositeAtlas was created to maximize the utility and value of the database.
31516400	3	29	theme	sample	524:529	arg1	type					531:534	specific sample type	515:534	specific sample type	515:534	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	7	30	from	studies	1429:1435	arg1	tissues					1379:1385	human-derived tissues	1365:1385	human-derived tissues	1365:1385	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	30	from	studies	1429:1435	arg1	fluids					1393:1398	body fluids	1388:1398	body fluids	1388:1398	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	30	from	studies	1429:1435	arg1	lines					1409:1413	cell lines	1404:1413	cell lines	1404:1413	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	2	31	theme	glycoprotein	413:424	arg1	structure					426:434	glycoprotein structure	413:434	glycoprotein structure	413:434	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	0	32	link	N-linked	72:79	arg1	glycoprotein					81:92	mass spectrometry-based human N-linked glycoprotein	42:92	mass spectrometry-based human N-linked glycoprotein	42:92	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	7	33	gly	N-glycoproteins	1305:1319	arg1	N-glycoproteins					1305:1319	more than 7200 N-glycoproteins	1290:1319	more than 7200 N-glycoproteins	1290:1319	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	4	34	from	publications	794:805	arg1	spectrometry					767:778	mass spectrometry	762:778	mass spectrometry from over 100 publications	762:805	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	4	34	from	publications	794:805	arg1	datasets					823:830	unpublished datasets	811:830	unpublished datasets generated from our laboratory	811:860	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	8	35	dep	CONCLUSIONS	1438:1448	arg1	//nglycositeatlas.biomarkercenter.org					1630:1666	//nglycositeatlas.biomarkercenter.org	1630:1666	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.	1438:1667	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	8	35	dep	CONCLUSIONS	1438:1448	arg1	downloaded					1577:1586	downloaded	1577:1586	can be downloaded from the N-GlycositeAtlas website at http	1570:1628	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	7	36	dep	RESULTS	1145:1151	arg1	contains					1183:1190	contains	1183:1190	contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1183:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	2	37	theme	function	448:455	arg1	interdependence					394:408	the interdependence	390:408	the interdependence of glycoprotein structure and protein function	390:455	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	0	38	theme	spectrometry-based	47:64	arg1	glycoprotein					81:92	mass spectrometry-based human N-linked glycoprotein	42:92	mass spectrometry-based human N-linked glycoprotein	42:92	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	0	39	dep	N-GlycositeAtlas	0:15	arg1	resource					29:36	a database resource	18:36	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.	0:124	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	7	40	theme	cell	1404:1407	arg1	lines					1409:1413	cell lines	1404:1413	cell lines	1404:1413	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	3	41	theme	glycoproteomic	565:578	arg1	data					580:583	glycoproteomic data	565:583	glycoproteomic data from different tissues, body fluids or cell types	565:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	4	42	gly	de-glycosylated	737:751	arg1	forms					753:757	their de-glycosylated forms	731:757	their de-glycosylated forms	731:757	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	3	43	theme	body	609:612	arg1	fluids					614:619	body fluids	609:619	body fluids	609:619	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	5	44	gly	glycoproteins	969:981	arg1	glycoproteins					969:981	glycoproteins	969:981	glycoproteins among different human cells, tissues and body fluids	969:1034	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	2	45	theme	spectrometry-based	319:336	arg1	glycoproteomics					338:352	mass spectrometry-based glycoproteomics	314:352	mass spectrometry-based glycoproteomics	314:352	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	5	46	theme	glycoproteins	969:981	arg1	analyses					957:964	the distribution analyses	940:964	the distribution analyses of glycoproteins among different human cells, tissues and body fluids	940:1034	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	6	47	theme	N-GlycositeAtlas	1065:1080	arg1	interface					1052:1060	a web interface	1046:1060	a web interface of N-GlycositeAtlas	1046:1080	Finally, a web interface of N-GlycositeAtlas was created to maximize the utility and value of the database.
31516400	4	48	theme	de-glycosylated	737:751	arg1	forms					753:757	their de-glycosylated forms	731:757	their de-glycosylated forms	731:757	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	7	49	theme	N-GlycositeAtlas	1157:1172	arg1	database					1174:1181	The N-GlycositeAtlas database	1153:1181	The N-GlycositeAtlas database	1153:1181	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	50	gly	N-glycosylation	1262:1276	arg2	peptides					1230:1237	more than 30,000 glycosite-containing peptides	1192:1237	more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1192:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	50	gly	N-glycosylation	1262:1276	arg2	sites					1278:1282	representing > 14,000 N-glycosylation sites	1240:1282	representing > 14,000 N-glycosylation sites	1240:1282	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	2	51	theme	valuable	367:374	arg1	insights					376:383	valuable insights	367:383	valuable insights into the interdependence of glycoprotein structure and protein function	367:455	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	8	52	theme	N-GlycositeAtlas	1597:1612	arg1	website					1614:1620	the N-GlycositeAtlas website	1593:1620	the N-GlycositeAtlas website	1593:1620	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	4	53	theme	human	676:680	arg1	peptides					703:710	the human glycosite-containing peptides	672:710	the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory	672:860	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	7	54	theme	biological	1336:1345	arg1	sources					1347:1353	different biological sources	1326:1353	different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1326:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	54	theme	biological	1336:1345	arg1	tissues					1379:1385	human-derived tissues	1365:1385	human-derived tissues	1365:1385	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	54	theme	biological	1336:1345	arg1	fluids					1393:1398	body fluids	1388:1398	body fluids	1388:1398	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	54	theme	biological	1336:1345	arg1	lines					1409:1413	cell lines	1404:1413	cell lines	1404:1413	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	4	55	dep	METHODS	636:642	arg1	collected					662:670	collected	662:670	collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory	662:860	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	2	56	theme	large-scale	243:253	arg1	characterization					255:270	The large-scale characterization	239:270	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics	239:352	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	1	57	theme	BACKGROUND	126:135	arg1	glycoprotein					146:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	1	57	theme	BACKGROUND	126:135	arg1	class					183:187	a highly interesting class	162:187	a highly interesting class of proteins for clinical and biological research	162:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	5	58	theme	body	1024:1027	arg1	fluids					1029:1034	body fluids	1024:1034	body fluids	1024:1034	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	3	59	from	types	629:633	arg1	integration					550:560	the integration	546:560	the integration of glycoproteomic data from different tissues, body fluids or cell types	546:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	3	59	from	types	629:633	arg1	data					580:583	glycoproteomic data	565:583	glycoproteomic data from different tissues, body fluids or cell types	565:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	0	60	theme	N-linked	72:79	arg1	glycoprotein					81:92	mass spectrometry-based human N-linked glycoprotein	42:92	mass spectrometry-based human N-linked glycoprotein	42:92	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	2	61	theme	glycoproteins	284:296	arg1	characterization					255:270	The large-scale characterization	239:270	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics	239:352	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	5	62	theme	different	989:997	arg1	cells					1005:1009	different human cells	989:1009	different human cells	989:1009	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	1	63	theme	N-linked	137:144	arg1	glycoprotein					146:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	1	63	theme	N-linked	137:144	arg1	class					183:187	a highly interesting class	162:187	a highly interesting class of proteins for clinical and biological research	162:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	8	64	theme	entire	1454:1459	arg1	database					1483:1490	The entire human N-glycoproteome database	1450:1490	The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids	1450:1568	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	3	65	from	tissues	600:606	arg1	integration					550:560	the integration	546:560	the integration of glycoproteomic data from different tissues, body fluids or cell types	546:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	3	65	from	tissues	600:606	arg1	data					580:583	glycoproteomic data	565:583	glycoproteomic data from different tissues, body fluids or cell types	565:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	1	66	theme	interesting	171:181	arg1	glycoprotein					146:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	1	66	theme	interesting	171:181	arg1	class					183:187	a highly interesting class	162:187	a highly interesting class of proteins for clinical and biological research	162:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	8	67	theme	N-glycoproteome	1467:1481	arg1	database					1483:1490	The entire human N-glycoproteome database	1450:1490	The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids	1450:1568	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	2	68	link	N-linked	275:282	arg1	glycoproteins					284:296	N-linked glycoproteins	275:296	N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics	275:352	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	0	69	theme	site	112:115	arg1	mapping					117:123	glycosylation site mapping	98:123	glycosylation site mapping	98:123	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	6	70	dep	utility	1110:1116	arg1	the					1106:1108	the	1106:1108	the	1106:1108	Finally, a web interface of N-GlycositeAtlas was created to maximize the utility and value of the database.
31516400	0	71	gly	glycoprotein	81:92	arg1	glycoprotein					81:92	mass spectrometry-based human N-linked glycoprotein	42:92	mass spectrometry-based human N-linked glycoprotein	42:92	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	3	72	theme	specific	515:522	arg1	type					531:534	specific sample type	515:534	specific sample type	515:534	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	0	73	gly	glycosylation	98:110	arg2	site					112:115	glycosylation site mapping	98:123	glycosylation site mapping	98:123	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	0	73	gly	glycosylation	98:110	arg2	mapping					117:123	glycosylation site mapping	98:123	glycosylation site mapping	98:123	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	4	74	theme	unpublished	811:821	arg1	datasets					823:830	unpublished datasets	811:830	unpublished datasets generated from our laboratory	811:860	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	0	75	theme	database	20:27	arg1	resource					29:36	a database resource	18:36	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.	0:124	N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
31516400	5	76	theme	database	865:872	arg1	resource					874:881	A database resource	863:881	A database resource termed N-GlycositeAtlas	863:905	A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids.
31516400	4	77	theme	mass	762:765	arg1	spectrometry					767:778	mass spectrometry	762:778	mass spectrometry from over 100 publications	762:805	METHODS In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory.
31516400	3	78	theme	type	531:534	arg1	analysis					503:510	the analysis	499:510	the analysis of specific sample type	499:534	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	7	79	theme	N-glycosylation	1262:1276	arg1	peptides					1230:1237	more than 30,000 glycosite-containing peptides	1192:1237	more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies	1192:1435	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	7	79	theme	N-glycosylation	1262:1276	arg1	sites					1278:1282	representing > 14,000 N-glycosylation sites	1240:1282	representing > 14,000 N-glycosylation sites	1240:1282	RESULTS The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies.
31516400	2	80	gly	glycoprotein	413:424	arg1	glycoprotein					413:424	glycoprotein structure	413:434	glycoprotein structure	413:434	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	8	81	theme	body	1558:1561	arg1	fluids					1563:1568	body fluids	1558:1568	body fluids	1558:1568	CONCLUSIONS The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.
31516400	3	82	theme	data	580:583	arg1	integration					550:560	the integration	546:560	the integration of glycoproteomic data from different tissues, body fluids or cell types	546:633	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31516400	1	83	link	N-linked	137:144	arg1	glycoprotein					146:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein	126:157	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	1	83	link	N-linked	137:144	arg1	class					183:187	a highly interesting class	162:187	a highly interesting class of proteins for clinical and biological research	162:236	BACKGROUND N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research.
31516400	2	84	theme	protein	440:446	arg1	function					448:455	protein function	440:455	protein function	440:455	The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function.
31516400	3	85	theme	different	590:598	arg1	tissues					600:606	different tissues	590:606	different tissues	590:606	However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types.
31450586	12	0	from	modifications	1687:1699	arg1	proteins					1742:1749	the extracellular matrix organization proteins	1704:1749	the extracellular matrix organization proteins	1704:1749	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	12	1	theme	N-glycosylation	1671:1685	arg1	modifications					1687:1699	N-glycosylation modifications	1671:1699	N-glycosylation modifications in the extracellular matrix organization proteins	1671:1749	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	12	1	theme	N-glycosylation	1671:1685	arg1	factor					1773:1778	a contributing factor	1758:1778	a contributing factor for the mesenchymal aggressive phenotype in non-type subtype	1758:1839	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	10	2	gly	glycosylation	1451:1463	arg2	site					1465:1468	the glycosylation site occupancy	1447:1478	the glycosylation site occupancy	1447:1478	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	10	2	gly	glycosylation	1451:1463	arg2	occupancy					1470:1478	the glycosylation site occupancy	1447:1478	the glycosylation site occupancy	1447:1478	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	7	3	link	N-linked	949:956	arg1	glycopeptides					958:970	1299 unique N-linked glycopeptides	937:970	1299 unique N-linked glycopeptides corresponding to 460 proteins	937:1000	We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins.
31450586	4	4	theme	disease	676:682	arg1	pathology					684:692	disease pathology	676:692	disease pathology	676:692	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	5	5	theme	glycosylation	748:760	arg1	analysis					727:734	the comparative analysis	711:734	the comparative analysis of N-linked glycosylation across bladder cancer subtypes	711:791	Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes.
31450586	2	6	theme	new	389:391	arg1	strategies					405:414	new therapeutic strategies	389:414	new therapeutic strategies	389:414	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	8	7	theme	non-type	1136:1143	arg1	subtypes					1145:1152	non-type subtypes	1136:1152	non-type subtypes	1136:1152	Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes.
31450586	5	8	theme	bladder	769:775	arg1	subtypes					784:791	bladder cancer subtypes	769:791	bladder cancer subtypes	769:791	Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes.
31450586	5	9	theme	comparative	715:725	arg1	analysis					727:734	the comparative analysis	711:734	the comparative analysis of N-linked glycosylation across bladder cancer subtypes	711:791	Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes.
31450586	2	10	theme	better	308:313	arg1	understanding					315:327	better understanding	308:327	better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies	308:414	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	1	11	theme	variable	203:210	arg1	outcomes					221:228	variable clinical outcomes	203:228	variable clinical outcomes	203:228	Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes.
31450586	2	12	theme	pathogenesis	336:347	arg1	understanding					315:327	better understanding	308:327	better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies	308:414	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	11	13	theme	matrix	1580:1585	arg1	organization					1587:1598	the extracellular matrix organization	1562:1598	the extracellular matrix organization pathway	1562:1606	Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma.
31450586	1	14	theme	metastatic	140:149	arg1	carcinoma					159:167	advanced and metastatic bladder carcinoma	127:167	advanced and metastatic bladder carcinoma	127:167	Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes.
31450586	3	15	contain	has	480:482	arg1	subtype					438:444	The non-type bladder subtype	417:444	The non-type bladder subtype	417:444	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	3	15	contain	has	480:482	arg1	mesenchymal					464:474	mesenchymal	464:474	mesenchymal	464:474	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	3	15	contain	has	480:482	arg2	features					496:503	mesenchymal features	484:503	mesenchymal features	484:503	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	8	16	link	N-linked	1042:1049	arg1	glycopeptides					1051:1063	118 unique N-linked glycopeptides	1031:1063	118 unique N-linked glycopeptides corresponding to 84 proteins	1031:1092	Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes.
31450586	1	17	theme	carcinoma	159:167	arg1	Treatment					114:122	Treatment	114:122	Treatment of advanced and metastatic bladder carcinoma	114:167	Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes.
31450586	12	18	theme	aggressive	1800:1809	arg1	phenotype					1811:1819	the mesenchymal aggressive phenotype	1784:1819	the mesenchymal aggressive phenotype in non-type subtype	1784:1839	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	10	19	theme	abundance	1412:1420	arg1	level					1422:1426	the protein abundance level	1400:1426	the protein abundance level	1400:1426	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	2	20	theme	carcinoma	285:293	arg1	subtype					266:272	this aggressive molecular subtype	240:272	this aggressive molecular subtype of bladder carcinoma	240:293	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	4	21	theme	oligosaccharide	568:582	arg1	residues					584:591	oligosaccharide residues	568:591	oligosaccharide residues	568:591	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	10	22	theme	glycosylation	1451:1463	arg1	occupancy					1470:1478	the glycosylation site occupancy	1447:1478	the glycosylation site occupancy	1447:1478	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	0	23	theme	Bladder	95:101	arg1	Carcinoma					103:111	Non-Type Bladder Carcinoma	86:111	Non-Type Bladder Carcinoma	86:111	N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma.
31450586	7	24	gly	glycopeptides	958:970	arg2	glycopeptides					958:970	1299 unique N-linked glycopeptides	937:970	1299 unique N-linked glycopeptides corresponding to 460 proteins	937:1000	We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins.
31450586	13	25	theme	therapeutic	1989:1999	arg1	targets					2001:2007	novel therapeutic targets	1983:2007	novel therapeutic targets	1983:2007	These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.
31450586	9	26	theme	expression	1283:1292	arg1	levels					1294:1299	their global protein expression levels	1262:1299	their global protein expression levels	1262:1299	Most of the altered glycoproteins were also observed with changes in their global protein expression levels.
31450586	6	27	theme	glycosite-containing	809:828	arg1	peptides					830:837	the glycosite-containing peptides	805:837	the glycosite-containing peptides	805:837	To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling.
31450586	9	28	gly	glycoproteins	1213:1225	arg1	glycoproteins					1213:1225	the altered glycoproteins	1201:1225	the altered glycoproteins	1201:1225	Most of the altered glycoproteins were also observed with changes in their global protein expression levels.
31450586	8	29	theme	unique	1035:1040	arg1	glycopeptides					1051:1063	118 unique N-linked glycopeptides	1031:1063	118 unique N-linked glycopeptides corresponding to 84 proteins	1031:1092	Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes.
31450586	3	30	theme	bladder	430:436	arg1	subtype					438:444	The non-type bladder subtype	417:444	The non-type bladder subtype	417:444	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	3	30	theme	bladder	430:436	arg1	mesenchymal					464:474	mesenchymal	464:474	mesenchymal	464:474	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	11	31	theme	bladder	1652:1658	arg1	carcinoma					1660:1668	bladder carcinoma	1652:1668	bladder carcinoma	1652:1668	Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma.
31450586	0	32	theme	N-Glycoproteomic	0:15	arg1	Profiling					17:25	N-Glycoproteomic Profiling	0:25	N-Glycoproteomic Profiling	0:25	N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma.
31450586	7	33	theme	unique	942:947	arg1	glycopeptides					958:970	1299 unique N-linked glycopeptides	937:970	1299 unique N-linked glycopeptides corresponding to 460 proteins	937:1000	We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins.
31450586	4	34	theme	cellular	638:645	arg1	functions					647:655	cellular functions	638:655	cellular functions	638:655	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	13	35	theme	glycan-based	1922:1933	arg1	therapies					1935:1943	glycan-based therapies	1922:1943	glycan-based therapies	1922:1943	These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.
31450586	9	36	theme	protein	1275:1281	arg1	levels					1294:1299	their global protein expression levels	1262:1299	their global protein expression levels	1262:1299	Most of the altered glycoproteins were also observed with changes in their global protein expression levels.
31450586	3	37	theme	metastatic	517:526	arg1	ability					528:534	a high metastatic ability	510:534	a high metastatic ability	510:534	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	1	38	theme	advanced	127:134	arg1	carcinoma					159:167	advanced and metastatic bladder carcinoma	127:167	advanced and metastatic bladder carcinoma	127:167	Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes.
31450586	9	39	theme	altered	1205:1211	arg1	glycoproteins					1213:1225	the altered glycoproteins	1201:1225	the altered glycoproteins	1201:1225	Most of the altered glycoproteins were also observed with changes in their global protein expression levels.
31450586	5	40	link	N-linked	739:746	arg1	glycosylation					748:760	N-linked glycosylation	739:760	N-linked glycosylation	739:760	Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes.
31450586	10	41	theme	expressed	1344:1352	arg1	glycoproteins					1354:1366	55 differentially expressed glycoproteins	1326:1366	55 differentially expressed glycoproteins	1326:1366	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	12	42	theme	contributing	1760:1771	arg1	modifications					1687:1699	N-glycosylation modifications	1671:1699	N-glycosylation modifications in the extracellular matrix organization proteins	1671:1749	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	12	42	theme	contributing	1760:1771	arg1	factor					1773:1778	a contributing factor	1758:1778	a contributing factor for the mesenchymal aggressive phenotype in non-type subtype	1758:1839	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	6	43	contain	carried	843:849	arg1	we					840:841	we	840:841	we	840:841	To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling.
31450586	6	43	contain	carried	843:849	arg2	profiling					912:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling.
31450586	4	44	theme	important	599:607	arg1	addition					556:563	Post-translational addition	537:563	Post-translational addition of oligosaccharide residues	537:591	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	4	44	theme	important	599:607	arg1	modification					609:620	an important modification	596:620	an important modification that influences cellular functions and contributes to disease pathology	596:692	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	13	45	theme	additional	1893:1902	arg1	avenues					1904:1910	additional avenues	1893:1910	additional avenues	1893:1910	These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.
31450586	6	46	theme	proteomic	883:891	arg1	profiling					912:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling.
31450586	0	47	theme	Matrix	63:68	arg1	Organization					70:81	Extracellular Matrix Organization	49:81	Extracellular Matrix Organization In Non-Type Bladder Carcinoma	49:111	N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma.
31450586	0	48	from	Alteration	35:44	arg1	Organization					70:81	Extracellular Matrix Organization	49:81	Extracellular Matrix Organization In Non-Type Bladder Carcinoma	49:111	N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma.
31450586	12	49	theme	matrix	1722:1727	arg1	proteins					1742:1749	the extracellular matrix organization proteins	1704:1749	the extracellular matrix organization proteins	1704:1749	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	6	50	theme	LC-MS/MS-based	855:868	arg1	profiling					912:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling.
31450586	10	51	theme	significant	1378:1388	arg1	change					1390:1395	no significant change	1375:1395	no significant change	1375:1395	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	11	52	theme	organization	1587:1598	arg1	pathway					1600:1606	the extracellular matrix organization pathway	1562:1606	the extracellular matrix organization pathway	1562:1606	Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma.
31450586	5	53	theme	N-linked	739:746	arg1	glycosylation					748:760	N-linked glycosylation	739:760	N-linked glycosylation	739:760	Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes.
31450586	2	54	theme	therapeutic	393:403	arg1	strategies					405:414	new therapeutic strategies	389:414	new therapeutic strategies	389:414	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	10	55	theme	protein	1404:1410	arg1	level					1422:1426	the protein abundance level	1400:1426	the protein abundance level	1400:1426	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	11	56	theme	non-type	1632:1639	arg1	subtype					1641:1647	the non-type subtype	1628:1647	the non-type subtype of bladder carcinoma	1628:1668	Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma.
31450586	10	57	from	alterations	1311:1321	arg1	glycoproteins					1354:1366	55 differentially expressed glycoproteins	1326:1366	55 differentially expressed glycoproteins	1326:1366	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	13	58	theme	protein	1857:1863	arg1	glycosylation					1865:1877	These aberrant protein glycosylation	1842:1877	These aberrant protein glycosylation	1842:1877	These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.
31450586	8	59	theme	luminal/basal	1169:1181	arg1	subtypes					1183:1190	luminal/basal subtypes	1169:1190	luminal/basal subtypes	1169:1190	Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes.
31450586	1	60	theme	clinical	212:219	arg1	outcomes					221:228	variable clinical outcomes	203:228	variable clinical outcomes	203:228	Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes.
31450586	6	61	theme	glycoproteomic	897:910	arg1	profiling					912:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling.
31450586	7	62	theme	460	989:991	arg1	proteins					993:1000	460 proteins	989:1000	460 proteins	989:1000	We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins.
31450586	11	63	theme	extracellular	1566:1578	arg1	organization					1587:1598	the extracellular matrix organization	1562:1598	the extracellular matrix organization pathway	1562:1606	Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma.
31450586	2	64	theme	bladder	277:283	arg1	carcinoma					285:293	bladder carcinoma	277:293	bladder carcinoma	277:293	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	5	65	theme	cancer	777:782	arg1	subtypes					784:791	bladder cancer subtypes	769:791	bladder cancer subtypes	769:791	Here, we report the comparative analysis of N-linked glycosylation across bladder cancer subtypes.
31450586	1	66	theme	bladder	151:157	arg1	carcinoma					159:167	advanced and metastatic bladder carcinoma	127:167	advanced and metastatic bladder carcinoma	127:167	Treatment of advanced and metastatic bladder carcinoma is often ineffective and displays variable clinical outcomes.
31450586	10	67	theme	luminal/basal	1525:1537	arg1	subtypes					1539:1546	the non-type subtype and luminal/basal subtypes	1500:1546	subtypes	1539:1546	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	0	68	theme	Non-Type	86:93	arg1	Carcinoma					103:111	Non-Type Bladder Carcinoma	86:111	Non-Type Bladder Carcinoma	86:111	N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma.
31450586	10	69	gly	glycoproteins	1354:1366	arg1	glycoproteins					1354:1366	55 differentially expressed glycoproteins	1326:1366	55 differentially expressed glycoproteins	1326:1366	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	12	70	theme	non-type	1824:1831	arg1	subtype					1833:1839	non-type subtype	1824:1839	non-type subtype	1824:1839	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	4	71	theme	residues	584:591	arg1	addition					556:563	Post-translational addition	537:563	Post-translational addition of oligosaccharide residues	537:591	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	4	71	theme	residues	584:591	arg1	modification					609:620	an important modification	596:620	an important modification that influences cellular functions and contributes to disease pathology	596:692	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	10	72	theme	site	1465:1468	arg1	occupancy					1470:1478	the glycosylation site occupancy	1447:1478	the glycosylation site occupancy	1447:1478	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	0	73	from	Organization	70:81	arg1	Carcinoma					103:111	Non-Type Bladder Carcinoma	86:111	Non-Type Bladder Carcinoma	86:111	N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma.
31450586	13	74	theme	novel	1983:1987	arg1	targets					2001:2007	novel therapeutic targets	1983:2007	novel therapeutic targets	1983:2007	These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.
31450586	12	75	from	phenotype	1811:1819	arg1	subtype					1833:1839	non-type subtype	1824:1839	non-type subtype	1824:1839	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	13	76	theme	aberrant	1848:1855	arg1	glycosylation					1865:1877	These aberrant protein glycosylation	1842:1877	These aberrant protein glycosylation	1842:1877	These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.
31450586	12	77	theme	mesenchymal	1788:1798	arg1	phenotype					1811:1819	the mesenchymal aggressive phenotype	1784:1819	the mesenchymal aggressive phenotype in non-type subtype	1784:1839	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	4	78	theme	Post-translational	537:554	arg1	addition					556:563	Post-translational addition	537:563	Post-translational addition of oligosaccharide residues	537:591	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	4	78	theme	Post-translational	537:554	arg1	modification					609:620	an important modification	596:620	an important modification that influences cellular functions and contributes to disease pathology	596:692	Post-translational addition of oligosaccharide residues is an important modification that influences cellular functions and contributes to disease pathology.
31450586	13	79	theme	targets	2001:2007	arg1	identification					1965:1978	the identification	1961:1978	the identification of novel therapeutic targets	1961:2007	These aberrant protein glycosylation would provide additional avenues to employ glycan-based therapies and may lead to the identification of novel therapeutic targets.
31450586	11	80	theme	carcinoma	1660:1668	arg1	subtype					1641:1647	the non-type subtype	1628:1647	the non-type subtype of bladder carcinoma	1628:1668	Importantly, the extracellular matrix organization pathway was dysregulated in the non-type subtype of bladder carcinoma.
31450586	9	81	theme	global	1268:1273	arg1	levels					1294:1299	their global protein expression levels	1262:1299	their global protein expression levels	1262:1299	Most of the altered glycoproteins were also observed with changes in their global protein expression levels.
31450586	3	82	theme	mesenchymal	484:494	arg1	features					496:503	mesenchymal features	484:503	mesenchymal features	484:503	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	7	83	theme	N-linked	949:956	arg1	glycopeptides					958:970	1299 unique N-linked glycopeptides	937:970	1299 unique N-linked glycopeptides corresponding to 460 proteins	937:1000	We identified 1299 unique N-linked glycopeptides corresponding to 460 proteins.
31450586	8	84	theme	N-linked	1042:1049	arg1	glycopeptides					1051:1063	118 unique N-linked glycopeptides	1031:1063	118 unique N-linked glycopeptides corresponding to 84 proteins	1031:1092	Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes.
31450586	3	85	theme	non-type	421:428	arg1	subtype					438:444	The non-type bladder subtype	417:444	The non-type bladder subtype	417:444	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	3	85	theme	non-type	421:428	arg1	mesenchymal					464:474	mesenchymal	464:474	mesenchymal	464:474	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	10	86	theme	non-type	1504:1511	arg1	subtype					1513:1519	the non-type subtype and luminal/basal subtypes	1500:1546	subtype	1513:1519	However, alterations in 55 differentially expressed glycoproteins showed no significant change at the protein abundance level, representing that the glycosylation site occupancy was changed between the non-type subtype and luminal/basal subtypes.
31450586	0	87	theme	Extracellular	49:61	arg1	Organization					70:81	Extracellular Matrix Organization	49:81	Extracellular Matrix Organization In Non-Type Bladder Carcinoma	49:111	N-Glycoproteomic Profiling Reveals Alteration In Extracellular Matrix Organization In Non-Type Bladder Carcinoma.
31450586	3	88	theme	high	512:515	arg1	ability					528:534	a high metastatic ability	510:534	a high metastatic ability	510:534	The non-type bladder subtype is phenotypically mesenchymal and has mesenchymal features with a high metastatic ability.
31450586	8	89	gly	glycopeptides	1051:1063	arg2	glycopeptides					1051:1063	118 unique N-linked glycopeptides	1031:1063	118 unique N-linked glycopeptides corresponding to 84 proteins	1031:1092	Additionally, we identified 118 unique N-linked glycopeptides corresponding to 84 proteins to be differentially glycosylated only in non-type subtypes as compared to luminal/basal subtypes.
31450586	2	90	theme	aggressive	245:254	arg1	subtype					266:272	this aggressive molecular subtype	240:272	this aggressive molecular subtype of bladder carcinoma	240:293	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	6	91	theme	quantitative	870:881	arg1	profiling					912:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	LC-MS/MS-based quantitative proteomic and glycoproteomic profiling	855:920	To analyze the glycosite-containing peptides, we carried out LC-MS/MS-based quantitative proteomic and glycoproteomic profiling.
31450586	12	92	theme	extracellular	1708:1720	arg1	proteins					1742:1749	the extracellular matrix organization proteins	1704:1749	the extracellular matrix organization proteins	1704:1749	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	12	93	theme	organization	1729:1740	arg1	proteins					1742:1749	the extracellular matrix organization proteins	1704:1749	the extracellular matrix organization proteins	1704:1749	N-glycosylation modifications in the extracellular matrix organization proteins may be a contributing factor for the mesenchymal aggressive phenotype in non-type subtype.
31450586	2	94	dep	aggressive	245:254	arg1	molecular					256:264	molecular	256:264	molecular	256:264	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
31450586	9	95	from	changes	1251:1257	arg1	levels					1294:1299	their global protein expression levels	1262:1299	their global protein expression levels	1262:1299	Most of the altered glycoproteins were also observed with changes in their global protein expression levels.
31450586	2	96	theme	strategies	405:414	arg1	identification					371:384	the identification	367:384	the identification of new therapeutic strategies	367:414	Studying this aggressive molecular subtype of bladder carcinoma will lead to better understanding of the pathogenesis which may lead to the identification of new therapeutic strategies.
29273674	7	0	theme	G-rich	1085:1090	arg1	motifs					1097:1102	3 G-rich loop motifs	1083:1102	3 G-rich loop motifs in Alg2	1083:1110	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	2	1	theme	unusual	366:372	arg1	Alg2					357:360	Alg2	357:360	Alg2	357:360	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	2	1	theme	unusual	366:372	arg1	MTase					395:399	MTase	395:399	MTase	395:399	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	2	1	theme	unusual	366:372	arg1	mannosyltransferase					374:392	an unusual mannosyltransferase	363:392	an unusual mannosyltransferase (MTase) with two different MTase activities	363:436	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	5	2	theme	Alg2-dependent	786:799	arg1	production					818:827	Alg2-dependent Man3GlcNAc2-PDol production	786:827	Alg2-dependent Man3GlcNAc2-PDol production	786:827	Alg2-dependent Man3GlcNAc2-PDol production relied on net-neutral lipids with a propensity to form bilayers.
29273674	1	3	theme	endoplasmic	273:283	arg1	reticulum					285:293	the endoplasmic reticulum	269:293	the endoplasmic reticulum	269:293	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	2	4	dep	α1,3-	457:461	arg1	an					454:455	an	454:455	an	454:455	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	1	5	from	synthesis	150:158	arg1	reticulum					285:293	the endoplasmic reticulum	269:293	the endoplasmic reticulum	269:293	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	7	6	theme	C-terminal	1029:1038	arg1	motif					1045:1049	The conserved C-terminal EX7E motif	1015:1049	The conserved C-terminal EX7E motif	1015:1049	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	8	7	theme	oligosaccharide.-Li	1386:1404	arg1	catalysis					1352:1360	Alg2 catalysis	1347:1360	Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D	1347:1494	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	2	8	theme	fifth	311:315	arg1	steps					317:321	The fourth and fifth steps	296:321	The fourth and fifth steps of LLO synthesis	296:338	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	1	9	dep	ordered	132:138	arg1	stepwise					141:148	stepwise	141:148	stepwise	141:148	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	8	10	theme	new	1286:1288	arg1	model					1290:1294	a new model	1284:1294	a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D	1284:1494	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	2	11	theme	core	525:528	arg1	Man3GlcNAc2-PDol					530:545	the trimannosyl core Man3GlcNAc2-PDol	509:545	the trimannosyl core Man3GlcNAc2-PDol	509:545	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	4	12	theme	liquid	640:645	arg1	assay					699:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	8	13	theme	trimannosyl	1369:1379	arg1	oligosaccharide.-Li					1386:1404	the trimannosyl core oligosaccharide.-Li	1365:1404	the trimannosyl core oligosaccharide.-Li	1365:1404	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	8	13	theme	trimannosyl	1369:1379	arg1	Wang					1414:1417	Wang	1414:1417	Wang	1414:1417	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	1	14	theme	lipid-linked	163:174	arg1	LLO					193:195	LLO	193:195	LLO	193:195	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	1	14	theme	lipid-linked	163:174	arg1	oligosaccharide					176:190	lipid-linked oligosaccharide	163:190	lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol)	163:264	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	2	15	theme	trimannosyl	513:523	arg1	Man3GlcNAc2-PDol					530:545	the trimannosyl core Man3GlcNAc2-PDol	509:545	the trimannosyl core Man3GlcNAc2-PDol	509:545	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	6	16	theme	α1,6-mannose	938:949	arg1	addition					912:919	addition	912:919	addition of the α1,3- and α1,6-mannose	912:949	We further showed addition of the α1,3- and α1,6-mannose can occur independently in either order but at differing rates.
29273674	5	17	theme	net-neutral	839:849	arg1	lipids					851:856	net-neutral lipids	839:856	net-neutral lipids with a propensity to form bilayers	839:891	Alg2-dependent Man3GlcNAc2-PDol production relied on net-neutral lipids with a propensity to form bilayers.
29273674	2	18	theme	fourth	300:305	arg1	steps					317:321	The fourth and fifth steps	296:321	The fourth and fifth steps of LLO synthesis	296:338	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	1	19	theme	oligosaccharide	176:190	arg1	Glc3Man9Gn2-PDol					248:263	Glc3Man9Gn2-PDol	248:263	Glc3Man9Gn2-PDol	248:263	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	1	19	theme	oligosaccharide	176:190	arg1	Glc3Man9GlcNAc2-pyrophosphate-dolichol					208:245	lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol	163:245	lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol)	163:264	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	1	20	link	lipid-linked	163:174	arg1	LLO					193:195	LLO	193:195	LLO	193:195	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	1	20	link	lipid-linked	163:174	arg1	oligosaccharide					176:190	lipid-linked oligosaccharide	163:190	lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol)	163:264	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	4	21	theme	Alg2	780:783	arg1	activities					751:760	the MTase activities	741:760	the MTase activities of purified yeast Alg2	741:783	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	4	22	theme	quantitative	686:697	arg1	assay					699:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	0	23	theme	Alternative	0:10	arg1	routes					12:17	Alternative routes	0:17	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.	0:80	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	8	24	theme	Alg2	1246:1249	arg1	bifunctionality					1227:1241	the unique bifunctionality	1216:1241	the unique bifunctionality of Alg2 during LLO synthesis	1216:1270	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	0	25	link	N-linked	36:43	arg1	glycans					45:51	N-linked glycans	36:51	N-linked glycans	36:51	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	2	26	theme	synthesis	330:338	arg1	steps					317:321	The fourth and fifth steps	296:321	The fourth and fifth steps of LLO synthesis	296:338	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	9	27	theme	Alternative	1497:1507	arg1	routes					1509:1514	Alternative routes	1497:1514	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.	1497:1577	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	4	28	used	used	725:728	arg2	assay					699:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	2	29	theme	LLO	326:328	arg1	synthesis					330:338	LLO synthesis	326:338	LLO synthesis	326:338	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	7	30	theme	conserved	1019:1027	arg1	motif					1045:1049	The conserved C-terminal EX7E motif	1015:1049	The conserved C-terminal EX7E motif	1015:1049	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	4	31	theme	chromatography/mass	647:665	arg1	assay					699:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	4	32	theme	yeast	774:778	arg1	Alg2					780:783	purified yeast Alg2	765:783	purified yeast Alg2	765:783	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	6	33	dep	showed	905:910	arg1	occur					955:959	occur	955:959	can occur independently in either order	951:989	We further showed addition of the α1,3- and α1,6-mannose can occur independently in either order but at differing rates.
29273674	6	33	dep	showed	905:910	arg1	rates					1008:1012	differing rates	998:1012	differing rates	998:1012	We further showed addition of the α1,3- and α1,6-mannose can occur independently in either order but at differing rates.
29273674	7	34	theme	crucial	1117:1123	arg1	roles					1125:1129	crucial roles	1117:1129	crucial roles	1117:1129	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	6	35	theme	α1,3-	928:932	arg1	addition					912:919	addition	912:919	addition of the α1,3- and α1,6-mannose	912:949	We further showed addition of the α1,3- and α1,6-mannose can occur independently in either order but at differing rates.
29273674	1	36	theme	-linked	97:103	arg1	glycosylation					105:117	Asparagine ( N)-linked glycosylation	82:117	Asparagine ( N)-linked glycosylation	82:117	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	1	37	theme	precursor	198:206	arg1	Glc3Man9Gn2-PDol					248:263	Glc3Man9Gn2-PDol	248:263	Glc3Man9Gn2-PDol	248:263	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	1	37	theme	precursor	198:206	arg1	Glc3Man9GlcNAc2-pyrophosphate-dolichol					208:245	lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol	163:245	lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol)	163:264	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	0	38	theme	N-linked	36:43	arg1	glycans					45:51	N-linked glycans	36:51	N-linked glycans	36:51	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	7	39	from	tail	1073:1076	arg1	Alg2					1107:1110	Alg2	1107:1110	Alg2	1107:1110	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	1	40	theme	Glc3Man9GlcNAc2-pyrophosphate-dolichol	208:245	arg1	synthesis					150:158	the ordered, stepwise synthesis	128:158	the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum	128:293	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	4	41	theme	spectrometry-based	667:684	arg1	assay					699:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	a liquid chromatography/mass spectrometry-based quantitative assay	638:703	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	2	42	theme	MTase	421:425	arg1	activities					427:436	two different MTase activities	407:436	two different MTase activities	407:436	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	5	43	with	lipids	851:856	arg1	propensity					865:874	a propensity	863:874	a propensity to form bilayers	863:891	Alg2-dependent Man3GlcNAc2-PDol production relied on net-neutral lipids with a propensity to form bilayers.
29273674	2	44	theme	different	411:419	arg1	activities					427:436	two different MTase activities	407:436	two different MTase activities	407:436	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	8	45	theme	LLO	1258:1260	arg1	synthesis					1262:1270	LLO synthesis	1258:1270	LLO synthesis	1258:1270	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	6	46	theme	differing	998:1006	arg1	rates					1008:1012	differing rates	998:1012	differing rates	998:1012	We further showed addition of the α1,3- and α1,6-mannose can occur independently in either order but at differing rates.
29273674	7	47	theme	loop	1092:1095	arg1	motifs					1097:1102	3 G-rich loop motifs	1083:1102	3 G-rich loop motifs in Alg2	1083:1110	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	0	48	theme	Alg2	56:59	arg1	mannosyltransferase					61:79	Alg2 mannosyltransferase	56:79	Alg2 mannosyltransferase	56:79	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	8	49	dep	exist	1337:1341	arg1	alternative					1305:1315	alternative	1305:1315	alternative	1305:1315	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	8	50	theme	core	1381:1384	arg1	oligosaccharide.-Li					1386:1404	the trimannosyl core oligosaccharide.-Li	1365:1404	the trimannosyl core oligosaccharide.-Li	1365:1404	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	8	50	theme	core	1381:1384	arg1	Wang					1414:1417	Wang	1414:1417	Wang	1414:1417	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	0	51	theme	glycans	45:51	arg1	synthesis					23:31	synthesis	23:31	synthesis of N-linked glycans by Alg2 mannosyltransferase	23:79	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	6	52	dep	α1,3-	928:932	arg1	the					924:926	the	924:926	the	924:926	We further showed addition of the α1,3- and α1,6-mannose can occur independently in either order but at differing rates.
29273674	9	53	theme	glycans	1542:1548	arg1	synthesis					1520:1528	synthesis	1520:1528	synthesis of N-linked glycans by Alg2 mannosyltransferase	1520:1576	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	7	54	theme	cytosolic	1063:1071	arg1	tail					1073:1076	N-terminal cytosolic tail	1052:1076	N-terminal cytosolic tail	1052:1076	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	4	55	theme	MTase	745:749	arg1	activities					751:760	the MTase activities	741:760	the MTase activities of purified yeast Alg2	741:783	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	9	56	theme	N-linked	1533:1540	arg1	glycans					1542:1548	N-linked glycans	1533:1548	N-linked glycans	1533:1548	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	9	57	link	N-linked	1533:1540	arg1	glycans					1542:1548	N-linked glycans	1533:1548	N-linked glycans	1533:1548	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	4	58	theme	purified	765:772	arg1	Alg2					780:783	purified yeast Alg2	765:783	purified yeast Alg2	765:783	In this study, a liquid chromatography/mass spectrometry-based quantitative assay was established and used to analyze the MTase activities of purified yeast Alg2.
29273674	3	59	theme	Alg2	578:581	arg1	properties					564:573	The biochemical properties	548:573	The biochemical properties of Alg2	548:581	The biochemical properties of Alg2 are controversial and remain undefined.
29273674	3	59	theme	Alg2	578:581	arg1	controversial					587:599	controversial	587:599	controversial	587:599	The biochemical properties of Alg2 are controversial and remain undefined.
29273674	3	60	theme	biochemical	552:562	arg1	properties					564:573	The biochemical properties	548:573	The biochemical properties of Alg2	548:581	The biochemical properties of Alg2 are controversial and remain undefined.
29273674	3	60	theme	biochemical	552:562	arg1	controversial					587:599	controversial	587:599	controversial	587:599	The biochemical properties of Alg2 are controversial and remain undefined.
29273674	9	61	theme	Alg2	1553:1556	arg1	mannosyltransferase					1558:1576	Alg2 mannosyltransferase	1553:1576	Alg2 mannosyltransferase	1553:1576	Alternative routes for synthesis of N-linked glycans by Alg2 mannosyltransferase.
29273674	1	62	theme	ordered	132:138	arg1	synthesis					150:158	the ordered, stepwise synthesis	128:158	the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum	128:293	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	8	63	theme	Alg2	1347:1350	arg1	catalysis					1352:1360	Alg2 catalysis	1347:1360	Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D	1347:1494	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	8	64	theme	independent	1318:1328	arg1	routes					1330:1335	independent routes	1318:1335	independent routes	1318:1335	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	5	65	theme	Man3GlcNAc2-PDol	801:816	arg1	production					818:827	Alg2-dependent Man3GlcNAc2-PDol production	786:827	Alg2-dependent Man3GlcNAc2-PDol production	786:827	Alg2-dependent Man3GlcNAc2-PDol production relied on net-neutral lipids with a propensity to form bilayers.
29273674	2	66	with	mannosyltransferase	374:392	arg1	activities					427:436	two different MTase activities	407:436	two different MTase activities	407:436	The fourth and fifth steps of LLO synthesis are catalyzed by Alg2, an unusual mannosyltransferase (MTase) with two different MTase activities; Alg2 adds both an α1,3- and α1,6-mannose onto ManGlcNAc2-PDol to form the trimannosyl core Man3GlcNAc2-PDol.
29273674	7	67	theme	N-terminal	1052:1061	arg1	tail					1073:1076	N-terminal cytosolic tail	1052:1076	N-terminal cytosolic tail	1052:1076	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	7	68	from	motif	1045:1049	arg1	Alg2					1107:1110	Alg2	1107:1110	Alg2	1107:1110	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	1	69	link	-linked	97:103	arg1	glycosylation					105:117	Asparagine ( N)-linked glycosylation	82:117	Asparagine ( N)-linked glycosylation	82:117	Asparagine ( N)-linked glycosylation requires the ordered, stepwise synthesis of lipid-linked oligosaccharide (LLO) precursor Glc3Man9GlcNAc2-pyrophosphate-dolichol (Glc3Man9Gn2-PDol) on the endoplasmic reticulum.
29273674	8	70	theme	unique	1220:1225	arg1	bifunctionality					1227:1241	the unique bifunctionality	1216:1241	the unique bifunctionality of Alg2 during LLO synthesis	1216:1270	These findings provide insight into the unique bifunctionality of Alg2 during LLO synthesis and lead to a new model in which alternative, independent routes exist for Alg2 catalysis of the trimannosyl core oligosaccharide.-Li, S.-T., Wang, N., Xu, X.-X., Fujita, M., Nakanishi, H., Kitajima, T., Dean, N., Gao, X.-D.
29273674	7	71	theme	EX7E	1040:1043	arg1	motif					1045:1049	The conserved C-terminal EX7E motif	1015:1049	The conserved C-terminal EX7E motif	1015:1049	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
29273674	7	72	from	motifs	1097:1102	arg1	Alg2					1107:1110	Alg2	1107:1110	Alg2	1107:1110	The conserved C-terminal EX7E motif, N-terminal cytosolic tail, and 3 G-rich loop motifs in Alg2 play crucial roles for these activities, both in vitro and in vivo.
30697857	5	0	theme	strict	666:671	arg1	control					681:687	the strict quality control	662:687	the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects)	662:836	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	4	1	theme	reduced	607:613	arg1	anticorrelation					619:633	a significantly reduced E-R anticorrelation	591:633	a significantly reduced E-R anticorrelation	591:633	We have recently shown that secreted proteins either lack an E-R anticorrelation or exhibit a significantly reduced E-R anticorrelation.
30697857	8	2	theme	E-R	1157:1159	arg1	correlation					1161:1171	a positive E-R correlation	1146:1171	a positive E-R correlation among N-glycosylated proteins	1146:1201	Strikingly, we observe a positive E-R correlation among N-glycosylated proteins.
30697857	5	3	theme	quality	673:679	arg1	control					681:687	the strict quality control	662:687	the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects)	662:836	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	7	4	theme	N-linked	1067:1074	arg1	glycosylation					1076:1088	N-linked glycosylation	1067:1088	N-linked glycosylation	1067:1088	Here, we investigate how N-linked glycosylation affects the E-R anticorrelation.
30697857	3	5	theme	rate	371:374	arg1	anticorrelation					382:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	4	6	theme	secreted	527:534	arg1	proteins					536:543	secreted proteins	527:543	secreted proteins	527:543	We have recently shown that secreted proteins either lack an E-R anticorrelation or exhibit a significantly reduced E-R anticorrelation.
30697857	9	7	theme	expressed	1289:1297	arg1	N-glycoproteins					1299:1313	lowly expressed N-glycoproteins	1283:1313	lowly expressed N-glycoproteins	1283:1313	That is, N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins.
30697857	2	8	theme	slow	299:302	arg1	rates					304:308	slow rates	299:308	slow rates	299:308	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	5	9	from	subject	720:726	arg1	reticulum					747:755	the endoplasmic reticulum	731:755	the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects)	731:836	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	9	10	theme	intracellular	1354:1366	arg1	proteins					1368:1375	intracellular proteins	1354:1375	intracellular proteins	1354:1375	That is, N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins.
30697857	4	11	theme	E-R	615:617	arg1	anticorrelation					619:633	a significantly reduced E-R anticorrelation	591:633	a significantly reduced E-R anticorrelation	591:633	We have recently shown that secreted proteins either lack an E-R anticorrelation or exhibit a significantly reduced E-R anticorrelation.
30697857	3	12	theme	expression	341:350	arg1	anticorrelation					382:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	1	13	theme	different	87:95	arg1	proteins					97:104	The different proteins	83:104	The different proteins of any proteome	83:120	The different proteins of any proteome evolve at enormously different rates.
30697857	3	14	theme	deleterious	446:456	arg1	effects					458:464	the abundance-dependent deleterious effects	422:464	the abundance-dependent deleterious effects of misfolding or misinteraction	422:496	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	3	15	theme	level-evolutionary	352:369	arg1	anticorrelation					382:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	9	16	theme	faster	1265:1270	arg1	rates					1272:1276	faster rates	1265:1276	faster rates than lowly expressed N-glycoproteins	1265:1313	That is, N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins.
30697857	6	17	gly	N-glycosylated	975:988	arg1	ones					990:993	N-glycosylated ones	975:993	N-glycosylated ones	975:993	Among secreted proteins, N-glycosylated ones are under particularly strong quality control.
30697857	5	18	theme	effects	940:946	arg1	rate					897:900	the rate	893:900	the rate of misinteraction and its deleterious effects	893:946	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	5	19	theme	deleterious	817:827	arg1	effects					829:835	its deleterious effects	813:835	its deleterious effects	813:835	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	2	20	with	level	240:244	arg1	proteins					269:276	highly expressed proteins	252:276	highly expressed proteins tending to evolve at slow rates	252:308	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	7	21	link	N-linked	1067:1074	arg1	glycosylation					1076:1088	N-linked glycosylation	1067:1088	N-linked glycosylation	1067:1088	Here, we investigate how N-linked glycosylation affects the E-R anticorrelation.
30697857	3	22	theme	abundance-dependent	426:444	arg1	effects					458:464	the abundance-dependent deleterious effects	422:464	the abundance-dependent deleterious effects of misfolding or misinteraction	422:496	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	3	23	theme	E-R	377:379	arg1	anticorrelation					382:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	the expression level-evolutionary rate (E-R) anticorrelation	337:396	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	1	24	theme	proteome	113:120	arg1	proteins					97:104	The different proteins	83:104	The different proteins of any proteome	83:120	The different proteins of any proteome evolve at enormously different rates.
30697857	5	25	theme	effects	829:835	arg1	rate					790:793	the rate	786:793	the rate of misfolding and its deleterious effects	786:835	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	3	26	theme	misinteraction	483:496	arg1	effects					458:464	the abundance-dependent deleterious effects	422:464	the abundance-dependent deleterious effects of misfolding or misinteraction	422:496	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	0	27	theme	level-evolutionary	46:63	arg1	correlation					70:80	a positive expression level-evolutionary rate correlation	24:80	a positive expression level-evolutionary rate correlation	24:80	N-glycoproteins exhibit a positive expression level-evolutionary rate correlation.
30697857	6	28	theme	secreted	956:963	arg1	proteins					965:972	secreted proteins	956:972	secreted proteins	956:972	Among secreted proteins, N-glycosylated ones are under particularly strong quality control.
30697857	0	29	gly	N-glycoproteins	0:14	arg1	N-glycoproteins					0:14	N-glycoproteins	0:14	N-glycoproteins	0:14	N-glycoproteins exhibit a positive expression level-evolutionary rate correlation.
30697857	9	30	gly	N-glycoproteins	1299:1313	arg1	N-glycoproteins					1299:1313	lowly expressed N-glycoproteins	1283:1313	lowly expressed N-glycoproteins	1283:1313	That is, N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins.
30697857	0	31	theme	expression	35:44	arg1	correlation					70:80	a positive expression level-evolutionary rate correlation	24:80	a positive expression level-evolutionary rate correlation	24:80	N-glycoproteins exhibit a positive expression level-evolutionary rate correlation.
30697857	9	32	dep	observed	1339:1346	arg1	contrast					1319:1326	contrast	1319:1326	contrast	1319:1326	That is, N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins.
30697857	5	33	theme	endoplasmic	735:745	arg1	reticulum					747:755	the endoplasmic reticulum	731:755	the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects)	731:836	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	2	34	theme	factors	179:185	arg1	One					160:162	One	160:162	One	160:162	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	2	34	theme	factors	179:185	arg1	factors					179:185	the primary factors	167:185	the primary factors influencing rates of protein evolution	167:224	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	0	35	theme	positive	26:33	arg1	correlation					70:80	a positive expression level-evolutionary rate correlation	24:80	a positive expression level-evolutionary rate correlation	24:80	N-glycoproteins exhibit a positive expression level-evolutionary rate correlation.
30697857	3	36	theme	misfolding	469:478	arg1	effects					458:464	the abundance-dependent deleterious effects	422:464	the abundance-dependent deleterious effects of misfolding or misinteraction	422:496	This phenomenon, known as the expression level-evolutionary rate (E-R) anticorrelation, has been attributed to the abundance-dependent deleterious effects of misfolding or misinteraction.
30697857	5	37	theme	misfolding	798:807	arg1	rate					790:793	the rate	786:793	the rate of misfolding and its deleterious effects	786:835	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	8	38	theme	N-glycosylated	1179:1192	arg1	proteins					1194:1201	N-glycosylated proteins	1179:1201	N-glycosylated proteins	1179:1201	Strikingly, we observe a positive E-R correlation among N-glycosylated proteins.
30697857	2	39	theme	primary	171:177	arg1	factors					179:185	the primary factors	167:185	the primary factors influencing rates of protein evolution	167:224	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	5	40	dep	location	864:871	arg1	expected					874:881	expected	874:881	expected to reduce the rate of misinteraction and its deleterious effects	874:946	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	5	41	theme	misinteraction	905:918	arg1	rate					897:900	the rate	893:900	the rate of misinteraction and its deleterious effects	893:946	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	0	42	theme	rate	65:68	arg1	correlation					70:80	a positive expression level-evolutionary rate correlation	24:80	a positive expression level-evolutionary rate correlation	24:80	N-glycoproteins exhibit a positive expression level-evolutionary rate correlation.
30697857	4	43	theme	E-R	560:562	arg1	anticorrelation					564:578	an E-R anticorrelation	557:578	an E-R anticorrelation	557:578	We have recently shown that secreted proteins either lack an E-R anticorrelation or exhibit a significantly reduced E-R anticorrelation.
30697857	5	44	theme	secreted	698:705	arg1	proteins					707:714	secreted proteins	698:714	secreted proteins	698:714	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	2	45	theme	expression	229:238	arg1	level					240:244	expression level	229:244	expression level	229:244	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	5	46	from	reticulum	747:755	arg1	subject					720:726	subject	720:726	subject	720:726	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	2	47	theme	evolution	216:224	arg1	rates					199:203	rates	199:203	rates of protein evolution	199:224	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	1	48	theme	different	143:151	arg1	rates					153:157	enormously different rates	132:157	enormously different rates	132:157	The different proteins of any proteome evolve at enormously different rates.
30697857	2	49	theme	protein	208:214	arg1	evolution					216:224	protein evolution	208:224	protein evolution	208:224	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	5	50	theme	deleterious	928:938	arg1	effects					940:946	its deleterious effects	924:946	its deleterious effects	924:946	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	7	51	theme	E-R	1102:1104	arg1	anticorrelation					1106:1120	the E-R anticorrelation	1098:1120	the E-R anticorrelation	1098:1120	Here, we investigate how N-linked glycosylation affects the E-R anticorrelation.
30697857	8	52	theme	positive	1148:1155	arg1	correlation					1161:1171	a positive E-R correlation	1146:1171	a positive E-R correlation among N-glycosylated proteins	1146:1201	Strikingly, we observe a positive E-R correlation among N-glycosylated proteins.
30697857	5	53	theme	extracellular	850:862	arg1	location					864:871	their extracellular location	844:871	their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects)	844:947	This effect may be due to the strict quality control to which secreted proteins are subject in the endoplasmic reticulum (which is expected to reduce the rate of misfolding and its deleterious effects) or to their extracellular location (expected to reduce the rate of misinteraction and its deleterious effects).
30697857	2	54	theme	expressed	259:267	arg1	proteins					269:276	highly expressed proteins	252:276	highly expressed proteins tending to evolve at slow rates	252:308	One of the primary factors influencing rates of protein evolution is expression level, with highly expressed proteins tending to evolve at slow rates.
30697857	8	55	gly	N-glycosylated	1179:1192	arg1	proteins					1194:1201	N-glycosylated proteins	1179:1201	N-glycosylated proteins	1179:1201	Strikingly, we observe a positive E-R correlation among N-glycosylated proteins.
30697857	6	56	theme	quality	1025:1031	arg1	control					1033:1039	particularly strong quality control	1005:1039	particularly strong quality control	1005:1039	Among secreted proteins, N-glycosylated ones are under particularly strong quality control.
30697857	9	57	gly	N-glycoproteins	1213:1227	arg1	N-glycoproteins					1213:1227	N-glycoproteins	1213:1227	N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins	1213:1375	That is, N-glycoproteins that are highly expressed evolve at faster rates than lowly expressed N-glycoproteins, in contrast to what is observed among intracellular proteins.
30697857	6	58	theme	N-glycosylated	975:988	arg1	ones					990:993	N-glycosylated ones	975:993	N-glycosylated ones	975:993	Among secreted proteins, N-glycosylated ones are under particularly strong quality control.
30697857	7	59	gly	glycosylation	1076:1088	arg1	E-R					1102:1104	the E-R anticorrelation	1098:1120	the E-R anticorrelation	1098:1120	Here, we investigate how N-linked glycosylation affects the E-R anticorrelation.
30697857	6	60	theme	strong	1018:1023	arg1	control					1033:1039	particularly strong quality control	1005:1039	particularly strong quality control	1005:1039	Among secreted proteins, N-glycosylated ones are under particularly strong quality control.
31671706	2	0	from	sites	404:408	arg1	region					436:441	the VEGFR-1 region	424:441	the VEGFR-1 region	424:441	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	0	from	sites	404:408	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	0	from	sites	404:408	arg1	region					469:474	the VEGFR-2 region	457:474	the VEGFR-2 region	457:474	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	5	1	gly	glycosylation	1013:1025	arg2	site					1027:1030	each glycosylation site	1008:1030	each glycosylation site	1008:1030	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	3	2	theme	tryptic	619:625	arg1	digests					627:633	the resulting tryptic digests	605:633	the resulting tryptic digests	605:633	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	1	3	theme	Fc	259:260	arg1	portion					262:268	the Fc portion	255:268	the Fc portion of human IgG1	255:282	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	4	4	theme	Integrated	866:875	arg1	I-GPA					901:905	I-GPA	901:905	I-GPA	901:905	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	4	4	theme	Integrated	866:875	arg1	Analyzer					891:898	Integrated GlycoProteome Analyzer	866:898	Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data	866:945	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	3	5	theme	chromatography-electrospray	659:685	arg1	spectrometry					710:721	liquid chromatography-electrospray ionization tandem mass spectrometry	652:721	liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS)	652:736	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	3	5	theme	chromatography-electrospray	659:685	arg1	MS/MS					731:735	LC-ESI MS/MS	724:735	LC-ESI MS/MS	724:735	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	4	6	theme	site-specific	814:826	arg1	mapping					841:847	site-specific glycopeptide mapping	814:847	site-specific glycopeptide mapping	814:847	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	6	7	theme	glycan	1229:1234	arg1	microheterogeneity					1236:1253	glycan microheterogeneity	1229:1253	glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein	1229:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	2	8	theme	human	497:501	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	3	9	theme	tandem	698:703	arg1	spectrometry					710:721	liquid chromatography-electrospray ionization tandem mass spectrometry	652:721	liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS)	652:736	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	3	9	theme	tandem	698:703	arg1	MS/MS					731:735	LC-ESI MS/MS	724:735	LC-ESI MS/MS	724:735	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	5	10	theme	different	1053:1061	arg1	patterns					1063:1070	significantly different patterns	1039:1070	significantly different patterns	1039:1070	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	4	11	theme	resulting	916:924	arg1	data					942:945	the resulting raw tandem mass data	912:945	the resulting raw tandem mass data	912:945	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	2	12	from	sites	448:452	arg1	region					436:441	the VEGFR-1 region	424:441	the VEGFR-1 region	424:441	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	12	from	sites	448:452	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	12	from	sites	448:452	arg1	region					469:474	the VEGFR-2 region	457:474	the VEGFR-2 region	457:474	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	5	13	link	N-linked	987:994	arg1	glycans					996:1002	N-linked glycans	987:1002	N-linked glycans for each glycosylation site	987:1030	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	6	14	theme	unique	1210:1215	arg1	features					1217:1224	the unique features	1206:1224	the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein	1206:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	3	15	theme	LC-ESI	724:729	arg1	spectrometry					710:721	liquid chromatography-electrospray ionization tandem mass spectrometry	652:721	liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS)	652:736	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	3	15	theme	LC-ESI	724:729	arg1	MS/MS					731:735	LC-ESI MS/MS	724:735	LC-ESI MS/MS	724:735	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	6	16	theme	protein	1308:1314	arg1	protein					1308:1314	VEGFR-IgG fusion protein	1291:1314	VEGFR-IgG fusion protein	1291:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	6	16	theme	protein	1308:1314	arg1	sites					1282:1286	the five glycosylation sites	1259:1286	the five glycosylation sites of VEGFR-IgG fusion protein	1259:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	5	17	theme	glycosylation	1013:1025	arg1	site					1027:1030	each glycosylation site	1008:1030	each glycosylation site	1008:1030	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	3	18	theme	site-specific	522:534	arg1	analysis					543:550	site-specific glycan analysis	522:550	site-specific glycan analysis	522:550	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	1	19	theme	fusion	140:145	arg1	protein					147:153	A biosimilar fusion protein VEGFR-IgG	127:163	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2)	127:249	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	2	20	theme	Fc	507:508	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	21	from	region	469:474	arg1	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	6	22	theme	VEGFR-IgG	1291:1299	arg1	protein					1308:1314	VEGFR-IgG fusion protein	1291:1314	VEGFR-IgG fusion protein	1291:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	2	23	theme	VEGFR-2	461:467	arg1	region					469:474	the VEGFR-2 region	457:474	the VEGFR-2 region	457:474	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	6	24	theme	mapping	1189:1195	arg1	results					1197:1203	the mapping results	1185:1203	the mapping results	1185:1203	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	5	25	gly	glycosylation	1141:1153	arg2	site					1155:1158	each glycosylation site	1136:1158	each glycosylation site	1136:1158	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	6	26	from	features	1217:1224	arg1	microheterogeneity					1236:1253	glycan microheterogeneity	1229:1253	glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein	1229:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	0	27	theme	N-Glycopeptide	75:88	arg1	Mapping					90:96	N-Glycopeptide Mapping	75:96	N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein	75:124	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	5	28	theme	certain	1114:1120	arg1	functions					1122:1130	certain functions	1114:1130	certain functions for each glycosylation site in the protein	1114:1173	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	6	29	theme	functional	1388:1397	arg1	meaning					1399:1405	the functional meaning	1384:1405	the functional meaning of each glycosylation pattern	1384:1435	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	1	30	theme	endothelial	188:198	arg1	factor					207:212	vascular endothelial growth factor receptors 1 and 2	179:230	vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2)	179:249	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	4	31	theme	tandem	930:935	arg1	data					942:945	the resulting raw tandem mass data	912:945	the resulting raw tandem mass data	912:945	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	0	32	from	Investigation	0:12	arg1	Microheterogeneity					53:70	Glycan Microheterogeneity	46:70	Glycan Microheterogeneity	46:70	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	0	33	theme	Fusion	111:116	arg1	Protein					118:124	VEGFR-IgG Fusion Protein	101:124	VEGFR-IgG Fusion Protein	101:124	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	0	34	from	Microheterogeneity	53:70	arg1	Investigation					0:12	Investigation	0:12	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.	0:125	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	1	35	theme	human	273:277	arg1	IgG1					279:282	human IgG1	273:282	human IgG1	273:282	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	2	36	theme	sites	415:419	arg1	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	0	37	theme	Site-Specific	17:29	arg1	Differences					31:41	Site-Specific Differences	17:41	Site-Specific Differences in Glycan Microheterogeneity	17:70	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	4	38	link	N-linked	752:759	arg1	sites					775:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	1	39	dep	receptors	214:222	arg1	2					230:230	2	230:230	2	230:230	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	1	39	dep	receptors	214:222	arg1	1					224:224	1	224:224	1	224:224	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	2	40	theme	glycosylation	390:402	arg1	sites					404:408	five N-linked glycosylation sites	376:408	five N-linked glycosylation sites	376:408	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	5	41	theme	glycosylation	1141:1153	arg1	site					1155:1158	each glycosylation site	1136:1158	each glycosylation site	1136:1158	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	2	42	from	total	367:371	arg1	region					436:441	the VEGFR-1 region	424:441	the VEGFR-1 region	424:441	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	42	from	total	367:371	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	42	from	total	367:371	arg1	region					469:474	the VEGFR-2 region	457:474	the VEGFR-2 region	457:474	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	4	43	gly	glycosylation	761:773	arg2	sites					775:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	0	44	from	Differences	31:41	arg1	Microheterogeneity					53:70	Glycan Microheterogeneity	46:70	Glycan Microheterogeneity	46:70	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	3	45	theme	resulting	609:617	arg1	digests					627:633	the resulting tryptic digests	605:633	the resulting tryptic digests	605:633	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	4	46	theme	expected	743:750	arg1	sites					775:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	2	47	theme	prepared	317:324	arg1	protein					333:339	The prepared fusion protein	313:339	The prepared fusion protein	313:339	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	48	from	site	485:488	arg1	region					436:441	the VEGFR-1 region	424:441	the VEGFR-1 region	424:441	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	48	from	site	485:488	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	48	from	site	485:488	arg1	region					469:474	the VEGFR-2 region	457:474	the VEGFR-2 region	457:474	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	4	49	theme	glycosylation	761:773	arg1	sites					775:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	5	50	from	functions	1122:1130	arg1	protein					1167:1173	the protein	1163:1173	the protein	1163:1173	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	6	51	theme	glycosylation	1268:1280	arg1	protein					1308:1314	VEGFR-IgG fusion protein	1291:1314	VEGFR-IgG fusion protein	1291:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	6	51	theme	glycosylation	1268:1280	arg1	sites					1282:1286	the five glycosylation sites	1259:1286	the five glycosylation sites of VEGFR-IgG fusion protein	1259:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	2	52	from	region	510:515	arg1	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	3	53	theme	ionization	687:696	arg1	spectrometry					710:721	liquid chromatography-electrospray ionization tandem mass spectrometry	652:721	liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS)	652:736	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	3	53	theme	ionization	687:696	arg1	MS/MS					731:735	LC-ESI MS/MS	724:735	LC-ESI MS/MS	724:735	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	1	54	theme	growth	200:205	arg1	factor					207:212	vascular endothelial growth factor receptors 1 and 2	179:230	vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2)	179:249	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	6	55	theme	glycosylation	1415:1427	arg1	pattern					1429:1435	each glycosylation pattern	1410:1435	each glycosylation pattern	1410:1435	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	3	56	theme	liquid	652:657	arg1	spectrometry					710:721	liquid chromatography-electrospray ionization tandem mass spectrometry	652:721	liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS)	652:736	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	3	56	theme	liquid	652:657	arg1	MS/MS					731:735	LC-ESI MS/MS	724:735	LC-ESI MS/MS	724:735	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	4	57	theme	glycopeptide	828:839	arg1	mapping					841:847	site-specific glycopeptide mapping	814:847	site-specific glycopeptide mapping	814:847	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	6	58	gly	glycosylation	1268:1280	arg1	protein					1308:1314	VEGFR-IgG fusion protein	1291:1314	VEGFR-IgG fusion protein	1291:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	6	58	gly	glycosylation	1268:1280	arg2	sites					1282:1286	the five glycosylation sites	1259:1286	the five glycosylation sites of VEGFR-IgG fusion protein	1259:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	6	58	gly	glycosylation	1268:1280	arg2	five					1263:1266	five	1263:1266	five	1263:1266	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	6	58	gly	glycosylation	1268:1280	arg2	protein					1308:1314	VEGFR-IgG fusion protein	1291:1314	VEGFR-IgG fusion protein	1291:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	3	59	theme	mass	705:708	arg1	spectrometry					710:721	liquid chromatography-electrospray ionization tandem mass spectrometry	652:721	liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS)	652:736	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	3	59	theme	mass	705:708	arg1	MS/MS					731:735	LC-ESI MS/MS	724:735	LC-ESI MS/MS	724:735	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	3	60	theme	glycan	536:541	arg1	analysis					543:550	site-specific glycan analysis	522:550	site-specific glycan analysis	522:550	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	4	61	gly	glycopeptide	828:839	arg2	glycopeptide					828:839	site-specific glycopeptide mapping	814:847	site-specific glycopeptide mapping	814:847	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	2	62	theme	site	485:488	arg1	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	1	63	theme	biosimilar	129:138	arg1	protein					147:153	A biosimilar fusion protein VEGFR-IgG	127:163	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2)	127:249	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	4	64	theme	GlycoProteome	877:889	arg1	I-GPA					901:905	I-GPA	901:905	I-GPA	901:905	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	4	64	theme	GlycoProteome	877:889	arg1	Analyzer					891:898	Integrated GlycoProteome Analyzer	866:898	Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data	866:945	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	2	65	link	N-linked	381:388	arg1	sites					404:408	five N-linked glycosylation sites	376:408	five N-linked glycosylation sites	376:408	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	6	66	theme	fusion	1301:1306	arg1	protein					1308:1314	VEGFR-IgG fusion protein	1291:1314	VEGFR-IgG fusion protein	1291:1314	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	3	67	theme	fusion	557:562	arg1	protein					564:570	the fusion protein	553:570	the fusion protein	553:570	For site-specific glycan analysis, the fusion protein was hydrolyzed with trypsin, and the resulting tryptic digests were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS).
31671706	2	68	theme	IgG	503:505	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	69	from	sites	415:419	arg1	region					436:441	the VEGFR-1 region	424:441	the VEGFR-1 region	424:441	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	69	from	sites	415:419	arg1	region					510:515	the human IgG Fc region	493:515	the human IgG Fc region	493:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	69	from	sites	415:419	arg1	region					469:474	the VEGFR-2 region	457:474	the VEGFR-2 region	457:474	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	0	70	theme	VEGFR-IgG	101:109	arg1	Protein					118:124	VEGFR-IgG Fusion Protein	101:124	VEGFR-IgG Fusion Protein	101:124	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	1	71	theme	vascular	179:186	arg1	factor					207:212	vascular endothelial growth factor receptors 1 and 2	179:230	vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2)	179:249	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	2	72	theme	sites	448:452	arg1	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	0	73	theme	Protein	118:124	arg1	Mapping					90:96	N-Glycopeptide Mapping	75:96	N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein	75:124	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	4	74	theme	raw	926:928	arg1	data					942:945	the resulting raw tandem mass data	912:945	the resulting raw tandem mass data	912:945	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	2	75	from	region	436:441	arg1	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	76	gly	glycosylation	390:402	arg2	sites					404:408	five N-linked glycosylation sites	376:408	five N-linked glycosylation sites	376:408	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	76	gly	glycosylation	390:402	arg2	five					376:379	five	376:379	five	376:379	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	4	77	theme	mass	937:940	arg1	data					942:945	the resulting raw tandem mass data	912:945	the resulting raw tandem mass data	912:945	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
31671706	2	78	contain	possess	357:363	arg1	protein					333:339	The prepared fusion protein	313:339	The prepared fusion protein	313:339	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	2	78	contain	possess	357:363	arg2	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	0	79	theme	Differences	31:41	arg1	Investigation					0:12	Investigation	0:12	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.	0:125	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	1	80	theme	IgG1	279:282	arg1	protein					147:153	A biosimilar fusion protein VEGFR-IgG	127:163	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2)	127:249	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	1	80	theme	IgG1	279:282	arg1	portion					262:268	the Fc portion	255:268	the Fc portion of human IgG1	255:282	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	2	81	theme	sites	404:408	arg1	total					367:371	a total	365:371	a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region	365:515	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	0	82	theme	Glycan	46:51	arg1	Microheterogeneity					53:70	Glycan Microheterogeneity	46:70	Glycan Microheterogeneity	46:70	Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein.
31671706	5	83	theme	N-linked	987:994	arg1	glycans					996:1002	N-linked glycans	987:1002	N-linked glycans for each glycosylation site	987:1030	Finally, it was clearly confirmed that N-linked glycans for each glycosylation site showed significantly different patterns in microheterogeneity, which may indicate certain functions for each glycosylation site in the protein.
31671706	2	84	theme	N-linked	381:388	arg1	sites					404:408	five N-linked glycosylation sites	376:408	five N-linked glycosylation sites	376:408	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	6	85	theme	pattern	1429:1435	arg1	meaning					1399:1405	the functional meaning	1384:1405	the functional meaning of each glycosylation pattern	1384:1435	Based on the mapping results, the unique features in glycan microheterogeneity for the five glycosylation sites of VEGFR-IgG fusion protein were compared site-specifically and further discussed to understand the functional meaning of each glycosylation pattern.
31671706	2	86	theme	VEGFR-1	428:434	arg1	region					436:441	the VEGFR-1 region	424:441	the VEGFR-1 region	424:441	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	1	87	dep	factor	207:212	arg1	receptors					214:222	receptors 1 and 2	214:230	vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2)	179:249	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	1	87	dep	factor	207:212	arg1	VEGFR-2					242:248	VEGFR-2	242:248	VEGFR-2	242:248	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	1	87	dep	factor	207:212	arg1	VEGFR-1					233:239	VEGFR-1	233:239	VEGFR-1	233:239	A biosimilar fusion protein VEGFR-IgG consisting of vascular endothelial growth factor receptors 1 and 2 (VEGFR-1, VEGFR-2) and the Fc portion of human IgG1 was prepared for this study.
31671706	2	88	theme	fusion	326:331	arg1	protein					333:339	The prepared fusion protein	313:339	The prepared fusion protein	313:339	The prepared fusion protein was expected to possess a total of five N-linked glycosylation sites: two sites in the VEGFR-1 region, two sites in the VEGFR-2 region, and one site in the human IgG Fc region.
31671706	4	89	theme	N-linked	752:759	arg1	sites					775:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites	739:779	The expected N-linked glycosylation sites were successfully identified and site-specific glycopeptide mapping was completed by Integrated GlycoProteome Analyzer (I-GPA) for the resulting raw tandem mass data.
30375453	10	0	theme	MD	1417:1418	arg1	simulations					1420:1430	standard MD simulations	1408:1430	standard MD simulations	1408:1430	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	7	1	theme	unfolding	902:910	arg1	sequence					912:919	This unfolding sequence	897:919	This unfolding sequence	897:919	This unfolding sequence varied due to protein-glycan interactions.
30375453	1	2	theme	multimeric	148:157	arg1	Factor					124:129	von Willebrand Factor	109:129	von Willebrand Factor (vWF)	109:135	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	1	2	theme	multimeric	148:157	arg1	protein					159:165	a large multimeric protein	140:165	a large multimeric protein that binds to platelets and collagen in blood clotting	140:220	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	10	3	theme	long-ranged	1487:1497	arg1	interactions					1514:1525	long-ranged protein-glycan interactions	1487:1525	long-ranged protein-glycan interactions	1487:1525	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	2	4	with	Disintegrin	278:288	arg1	motif					339:343	a ThromboSpondin type 1 motif	315:343	a ThromboSpondin type 1 motif	315:343	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	2	4	with	Disintegrin	278:288	arg1	member					346:351	member 13	346:354	member 13	346:354	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	0	5	theme	Mechanical	87:96	arg1	Unfolding					98:106	Mechanical Unfolding	87:106	Mechanical Unfolding	87:106	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	9	6	link	N-linked	1148:1155	arg1	glycans					1157:1163	N-linked glycans	1148:1163	N-linked glycans	1148:1163	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	2	7	dep	ADAMTS13	266:273	arg1	Disintegrin					278:288	A Disintegrin	276:288	A Disintegrin	276:288	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	2	7	dep	ADAMTS13	266:273	arg1	Metalloprotease					294:308	Metalloprotease	294:308	Metalloprotease	294:308	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	10	8	theme	standard	1408:1415	arg1	simulations					1420:1430	standard MD simulations	1408:1430	standard MD simulations	1408:1430	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	6	9	theme	β-strands	822:830	arg1	pullout					811:817	The sequential pullout	796:817	The sequential pullout of β-strands	796:830	The sequential pullout of β-strands was used to represent a characteristic unfolding sequence of A2.
30375453	10	10	theme	A2	1351:1352	arg1	structure					1361:1369	A2 domain structure	1351:1369	A2 domain structure itself with and without glycans from standard MD simulations	1351:1430	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	5	11	theme	A2	725:726	arg1	domain					728:733	A2 domain	725:733	A2 domain	725:733	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	2	12	with	Metalloprotease	294:308	arg1	motif					339:343	a ThromboSpondin type 1 motif	315:343	a ThromboSpondin type 1 motif	315:343	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	2	12	with	Metalloprotease	294:308	arg1	member					346:351	member 13	346:354	member 13	346:354	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	9	13	theme	ADAMTS13	1261:1268	arg1	site					1279:1282	ADAMTS13 cleavage site	1261:1282	ADAMTS13 cleavage site exposure	1261:1291	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	3	14	theme	flowing	517:523	arg1	blood					525:529	flowing blood	517:529	flowing blood	517:529	This regulation process is highly sensitive to force conditions and protein-glycan interactions as the process occurs in flowing blood.
30375453	9	15	theme	N-linked	1148:1155	arg1	glycans					1157:1163	N-linked glycans	1148:1163	N-linked glycans	1148:1163	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	3	16	theme	protein-glycan	464:477	arg1	interactions					479:490	protein-glycan interactions	464:490	protein-glycan interactions	464:490	This regulation process is highly sensitive to force conditions and protein-glycan interactions as the process occurs in flowing blood.
30375453	8	17	theme	total	988:992	arg1	profiles					1011:1018	The force-extension and total energy-extension profiles	964:1018	profiles	1011:1018	The force-extension and total energy-extension profiles also show differences in magnitude but similar characteristic shapes between the systems with and without glycans.
30375453	4	18	from	sites	546:550	arg1	domain					558:563	A2 domain	555:563	A2 domain (N1515 and N1574) bearing various N-linked glycan structures	555:624	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	9	19	theme	cleavage	1270:1277	arg1	site					1279:1282	ADAMTS13 cleavage site	1261:1282	ADAMTS13 cleavage site exposure	1261:1291	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	8	20	theme	energy-extension	994:1009	arg1	profiles					1011:1018	The force-extension and total energy-extension profiles	964:1018	profiles	1011:1018	The force-extension and total energy-extension profiles also show differences in magnitude but similar characteristic shapes between the systems with and without glycans.
30375453	10	21	from	simulations	1420:1430	arg1	glycans					1395:1401	glycans	1395:1401	glycans from standard MD simulations	1395:1430	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	5	22	used	used	645:648	arg2	we					642:643	we	642:643	we	642:643	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	4	23	theme	glycan	608:613	arg1	structures					615:624	various N-linked glycan structures	591:624	various N-linked glycan structures	591:624	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	5	24	theme	domain	728:733	arg1	unfolding					712:720	the force-induced unfolding	694:720	the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site	694:793	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	6	25	theme	sequential	800:809	arg1	pullout					811:817	The sequential pullout	796:817	The sequential pullout of β-strands	796:830	The sequential pullout of β-strands was used to represent a characteristic unfolding sequence of A2.
30375453	5	26	link	N-linked	761:768	arg1	type					777:780	a single N-linked glycan type	752:780	a single N-linked glycan type on each site	752:793	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	3	27	theme	regulation	401:410	arg1	process					412:418	This regulation process	396:418	This regulation process	396:418	This regulation process is highly sensitive to force conditions and protein-glycan interactions as the process occurs in flowing blood.
30375453	0	28	theme	Protein-glycan	12:25	arg1	Interactions					27:38	Long-ranged Protein-glycan Interactions	0:38	Long-ranged Protein-glycan Interactions	0:38	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	5	29	theme	force-induced	698:710	arg1	unfolding					712:720	the force-induced unfolding	694:720	the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site	694:793	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	9	30	theme	higher	1177:1182	arg1	barriers					1191:1198	higher energy barriers	1177:1198	higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure	1177:1291	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	0	31	theme	Long-ranged	0:10	arg1	Interactions					27:38	Long-ranged Protein-glycan Interactions	0:38	Long-ranged Protein-glycan Interactions	0:38	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	9	32	dep	point	1252:1256	arg1	up					1242:1243	up	1242:1243	up	1242:1243	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	9	33	theme	exposure	1284:1291	arg1	point					1252:1256	the point	1248:1256	the point of ADAMTS13 cleavage site exposure	1248:1291	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	9	34	theme	energy	1184:1189	arg1	barriers					1191:1198	higher energy barriers	1177:1198	higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure	1177:1291	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	1	35	theme	von	109:111	arg1	protein					159:165	a large multimeric protein	140:165	a large multimeric protein that binds to platelets and collagen in blood clotting	140:220	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	1	35	theme	von	109:111	arg1	vWF					132:134	vWF	132:134	vWF	132:134	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	1	35	theme	von	109:111	arg1	Factor					124:129	von Willebrand Factor	109:129	von Willebrand Factor (vWF)	109:135	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	9	36	theme	full	1204:1207	arg1	unfolding					1209:1217	full unfolding	1204:1217	full unfolding	1204:1217	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	6	37	theme	A2	893:894	arg1	sequence					881:888	a characteristic unfolding sequence	854:888	a characteristic unfolding sequence of A2	854:894	The sequential pullout of β-strands was used to represent a characteristic unfolding sequence of A2.
30375453	1	38	theme	Willebrand	113:122	arg1	protein					159:165	a large multimeric protein	140:165	a large multimeric protein that binds to platelets and collagen in blood clotting	140:220	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	1	38	theme	Willebrand	113:122	arg1	vWF					132:134	vWF	132:134	vWF	132:134	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	1	38	theme	Willebrand	113:122	arg1	Factor					124:129	von Willebrand Factor	109:129	von Willebrand Factor (vWF)	109:135	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	10	39	theme	domain	1354:1359	arg1	structure					1361:1369	A2 domain structure	1351:1369	A2 domain structure itself with and without glycans from standard MD simulations	1351:1430	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	2	40	theme	vWF	381:383	arg1	multimers					385:393	vWF multimers	381:393	vWF multimers	381:393	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	2	41	theme	multimers	385:393	arg1	size					373:376	the size	369:376	the size of vWF multimers	369:393	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	10	42	theme	N-glycans	1453:1461	arg1	roles					1444:1448	roles	1444:1448	roles of N-glycans in A2 unfolding	1444:1477	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	0	43	from	Unfolding	98:106	arg1	Domain					75:80	von Willebrand Factor A2 Domain	50:80	von Willebrand Factor A2 Domain from Mechanical Unfolding	50:106	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	5	44	theme	N-linked	761:768	arg1	type					777:780	a single N-linked glycan type	752:780	a single N-linked glycan type on each site	752:793	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	0	45	theme	Willebrand	54:63	arg1	Domain					75:80	von Willebrand Factor A2 Domain	50:80	von Willebrand Factor A2 Domain from Mechanical Unfolding	50:106	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	5	46	theme	molecular	650:658	arg1	MD					670:671	MD	670:671	MD	670:671	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	5	46	theme	molecular	650:658	arg1	dynamics					660:667	molecular dynamics	650:667	molecular dynamics (MD) simulation	650:683	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	5	47	theme	glycan	770:775	arg1	type					777:780	a single N-linked glycan type	752:780	a single N-linked glycan type on each site	752:793	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	2	48	theme	A2	227:228	arg1	domain					230:235	vWF A2 domain	223:235	vWF A2 domain	223:235	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	4	49	theme	various	591:597	arg1	structures					615:624	various N-linked glycan structures	591:624	various N-linked glycan structures	591:624	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	0	50	theme	von	50:52	arg1	Domain					75:80	von Willebrand Factor A2 Domain	50:80	von Willebrand Factor A2 Domain from Mechanical Unfolding	50:106	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	6	51	theme	unfolding	871:879	arg1	sequence					881:888	a characteristic unfolding sequence	854:888	a characteristic unfolding sequence of A2	854:894	The sequential pullout of β-strands was used to represent a characteristic unfolding sequence of A2.
30375453	5	52	theme	dynamics	660:667	arg1	simulation					674:683	molecular dynamics (MD) simulation	650:683	molecular dynamics (MD) simulation	650:683	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	2	53	theme	vWF	223:225	arg1	domain					230:235	vWF A2 domain	223:235	vWF A2 domain	223:235	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	7	54	theme	protein-glycan	935:948	arg1	interactions					950:961	protein-glycan interactions	935:961	protein-glycan interactions	935:961	This unfolding sequence varied due to protein-glycan interactions.
30375453	1	55	theme	blood	207:211	arg1	clotting					213:220	blood clotting	207:220	blood clotting	207:220	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	0	56	theme	A2	72:73	arg1	Domain					75:80	von Willebrand Factor A2 Domain	50:80	von Willebrand Factor A2 Domain from Mechanical Unfolding	50:106	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	6	57	theme	characteristic	856:869	arg1	sequence					881:888	a characteristic unfolding sequence	854:888	a characteristic unfolding sequence of A2	854:894	The sequential pullout of β-strands was used to represent a characteristic unfolding sequence of A2.
30375453	8	58	theme	similar	1059:1065	arg1	shapes					1082:1087	similar characteristic shapes	1059:1087	similar characteristic shapes	1059:1087	The force-extension and total energy-extension profiles also show differences in magnitude but similar characteristic shapes between the systems with and without glycans.
30375453	5	59	from	type	777:780	arg1	site					790:793	each site	785:793	each site	785:793	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	2	60	theme	type	332:335	arg1	motif					339:343	a ThromboSpondin type 1 motif	315:343	a ThromboSpondin type 1 motif	315:343	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	2	60	theme	type	332:335	arg1	member					346:351	member 13	346:354	member 13	346:354	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	0	61	theme	Factor	65:70	arg1	Domain					75:80	von Willebrand Factor A2 Domain	50:80	von Willebrand Factor A2 Domain from Mechanical Unfolding	50:106	Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding.
30375453	9	62	with	Systems	1135:1141	arg1	glycans					1157:1163	N-linked glycans	1148:1163	N-linked glycans	1148:1163	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	4	63	link	N-linked	599:606	arg1	structures					615:624	various N-linked glycan structures	591:624	various N-linked glycan structures	591:624	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	2	64	theme	ThromboSpondin	317:330	arg1	type					332:335	ThromboSpondin type 1	317:337	a ThromboSpondin type 1 motif	315:343	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	9	65	theme	site	1279:1282	arg1	exposure					1284:1291	ADAMTS13 cleavage site exposure	1261:1291	ADAMTS13 cleavage site exposure	1261:1291	Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure.
30375453	2	66	theme	proteolytic	245:255	arg1	site					257:260	a proteolytic site	243:260	a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers	243:393	vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers.
30375453	8	67	theme	characteristic	1067:1080	arg1	shapes					1082:1087	similar characteristic shapes	1059:1087	similar characteristic shapes	1059:1087	The force-extension and total energy-extension profiles also show differences in magnitude but similar characteristic shapes between the systems with and without glycans.
30375453	3	68	theme	force	443:447	arg1	conditions					449:458	force conditions	443:458	force conditions	443:458	This regulation process is highly sensitive to force conditions and protein-glycan interactions as the process occurs in flowing blood.
30375453	10	69	from	roles	1444:1448	arg1	unfolding					1469:1477	A2 unfolding	1466:1477	A2 unfolding	1466:1477	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	4	70	dep	domain	558:563	arg1	N1574					576:580	N1574	576:580	N1574	576:580	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	4	70	dep	domain	558:563	arg1	N1515					566:570	N1515	566:570	N1515	566:570	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	6	71	used	used	836:839	arg2	pullout					811:817	The sequential pullout	796:817	The sequential pullout of β-strands	796:830	The sequential pullout of β-strands was used to represent a characteristic unfolding sequence of A2.
30375453	5	72	theme	single	754:759	arg1	type					777:780	a single N-linked glycan type	752:780	a single N-linked glycan type on each site	752:793	In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site.
30375453	10	73	theme	protein-glycan	1499:1512	arg1	interactions					1514:1525	long-ranged protein-glycan interactions	1487:1525	long-ranged protein-glycan interactions	1487:1525	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
30375453	4	74	theme	N-linked	599:606	arg1	structures					615:624	various N-linked glycan structures	591:624	various N-linked glycan structures	591:624	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	8	75	from	differences	1030:1040	arg1	magnitude					1045:1053	magnitude	1045:1053	magnitude	1045:1053	The force-extension and total energy-extension profiles also show differences in magnitude but similar characteristic shapes between the systems with and without glycans.
30375453	8	75	from	differences	1030:1040	arg1	shapes					1082:1087	similar characteristic shapes	1059:1087	similar characteristic shapes	1059:1087	The force-extension and total energy-extension profiles also show differences in magnitude but similar characteristic shapes between the systems with and without glycans.
30375453	4	76	theme	A2	555:556	arg1	domain					558:563	A2 domain	555:563	A2 domain (N1515 and N1574) bearing various N-linked glycan structures	555:624	There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures.
30375453	1	77	theme	large	142:146	arg1	Factor					124:129	von Willebrand Factor	109:129	von Willebrand Factor (vWF)	109:135	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	1	77	theme	large	142:146	arg1	protein					159:165	a large multimeric protein	140:165	a large multimeric protein that binds to platelets and collagen in blood clotting	140:220	von Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting.
30375453	10	78	theme	A2	1466:1467	arg1	unfolding					1469:1477	A2 unfolding	1466:1477	A2 unfolding	1466:1477	Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
32010524	0	0	with	microorganisms	31:44	arg1	spectroscopy					61:72	terahertz spectroscopy	51:72	terahertz spectroscopy	51:72	Identifying different types of microorganisms with terahertz spectroscopy.
32010524	9	1	theme	long	1383:1386	arg1	branches					1388:1395	short and long branches	1373:1395	short and long branches	1373:1395	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	6	2	theme	microfluidic	910:921	arg1	metamaterials					923:935	microfluidic metamaterials	910:935	microfluidic metamaterials	910:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	2	3	theme	frequency	358:366	arg1	range					368:372	the THz frequency range	350:372	the THz frequency range	350:372	Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range.
32010524	9	4	theme	main	1448:1451	arg1	composition					1428:1438	cell wall composition	1418:1438	cell wall composition	1418:1438	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	4	theme	main	1448:1451	arg1	cause					1453:1457	the main cause	1444:1457	the main cause of the observed differences in dielectric constants for different types of microorganisms	1444:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	4	5	theme	dielectric	571:580	arg1	1.24-1.85					608:616	1.24-1.85	608:616	1.24-1.85	608:616	The dielectric constant of the molds was 1.24-1.85, which was lower than that of bacteria ranging from 2.75-4.11.
32010524	4	5	theme	dielectric	571:580	arg1	constant					582:589	The dielectric constant	567:589	The dielectric constant of the molds	567:602	The dielectric constant of the molds was 1.24-1.85, which was lower than that of bacteria ranging from 2.75-4.11.
32010524	5	6	theme	dielectric	720:729	arg1	constants					731:739	particularly high dielectric constants	702:739	particularly high dielectric constants	702:739	The yeasts exhibited particularly high dielectric constants reaching 5.63-5.97, which were even higher than that of water.
32010524	9	7	theme	differences	1475:1485	arg1	composition					1428:1438	cell wall composition	1418:1438	cell wall composition	1418:1438	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	7	theme	differences	1475:1485	arg1	cause					1453:1457	the main cause	1444:1457	the main cause of the observed differences in dielectric constants for different types of microorganisms	1444:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	2	8	from	constants	337:345	arg1	range					368:372	the THz frequency range	350:372	the THz frequency range	350:372	Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range.
32010524	3	9	theme	effective	542:550	arg1	theory					559:564	the effective medium theory	538:564	the effective medium theory	538:564	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
32010524	7	10	theme	blue	955:958	arg1	shift					960:964	a blue shift	953:964	a blue shift in the metamaterial resonance	953:994	In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment.
32010524	1	11	theme	Most	75:78	arg1	techniques					100:109	Most microbial detection techniques	75:109	Most microbial detection techniques	75:109	Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes.
32010524	6	12	from	environment	892:902	arg1	results					842:848	the results	838:848	the results of low-density measurements in an aqueous environment using microfluidic metamaterials	838:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	6	13	theme	aqueous	884:890	arg1	environment					892:902	an aqueous environment	881:902	an aqueous environment using microfluidic metamaterials	881:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	9	14	from	differences	1475:1485	arg1	constants					1501:1509	dielectric constants	1490:1509	dielectric constants for different types of microorganisms	1490:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	1	15	theme	microbial	80:88	arg1	techniques					100:109	Most microbial detection techniques	75:109	Most microbial detection techniques	75:109	Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes.
32010524	9	16	from	constants	1501:1509	arg1	composition					1428:1438	cell wall composition	1418:1438	cell wall composition	1418:1438	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	16	from	constants	1501:1509	arg1	cause					1453:1457	the main cause	1444:1457	the main cause of the observed differences in dielectric constants for different types of microorganisms	1444:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	17	theme	wall	1423:1426	arg1	composition					1428:1438	cell wall composition	1418:1438	cell wall composition	1418:1438	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	17	theme	wall	1423:1426	arg1	cause					1453:1457	the main cause	1444:1457	the main cause of the observed differences in dielectric constants for different types of microorganisms	1444:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	7	18	theme	aqueous	1096:1102	arg1	environment					1104:1114	the aqueous environment	1092:1114	the aqueous environment	1092:1114	In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment.
32010524	9	19	with	chitin	1335:1340	arg1	branches					1388:1395	short and long branches	1373:1395	short and long branches	1373:1395	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	1	20	theme	detection	90:98	arg1	techniques					100:109	Most microbial detection techniques	75:109	Most microbial detection techniques	75:109	Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes.
32010524	7	21	contain	have	1047:1050	arg1	molds					1041:1045	the molds	1037:1045	the molds	1037:1045	In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment.
32010524	7	21	contain	have	1047:1050	arg2	contrast					1059:1066	higher contrast	1052:1066	higher contrast relative to bacteria	1052:1087	In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment.
32010524	3	22	theme	wide	446:449	arg1	range					451:455	a wide range	444:455	a wide range of microbial species	444:476	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
32010524	0	23	theme	different	12:20	arg1	types					22:26	different types	12:26	different types of microorganisms with terahertz spectroscopy	12:72	Identifying different types of microorganisms with terahertz spectroscopy.
32010524	9	24	theme	polysaccharides	1311:1325	arg1	chitin					1335:1340	chitin	1335:1340	chitin	1335:1340	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	24	theme	polysaccharides	1311:1325	arg1	constants					1280:1288	the dielectric constants	1265:1288	the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches)	1265:1396	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	24	theme	polysaccharides	1311:1325	arg1	α-glucan					1343:1350	α-glucan	1343:1350	α-glucan	1343:1350	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	24	theme	polysaccharides	1311:1325	arg1	β-glucans					1357:1365	β-glucans	1357:1365	β-glucans (with short and long branches)	1357:1396	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	2	25	theme	dielectric	326:335	arg1	constants					337:345	their intrinsic dielectric constants	310:345	their intrinsic dielectric constants in the THz frequency range	310:372	Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range.
32010524	9	26	theme	peptidoglycan	1293:1305	arg1	chitin					1335:1340	chitin	1335:1340	chitin	1335:1340	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	26	theme	peptidoglycan	1293:1305	arg1	constants					1280:1288	the dielectric constants	1265:1288	the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches)	1265:1396	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	26	theme	peptidoglycan	1293:1305	arg1	α-glucan					1343:1350	α-glucan	1343:1350	α-glucan	1343:1350	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	26	theme	peptidoglycan	1293:1305	arg1	β-glucans					1357:1365	β-glucans	1357:1365	β-glucans (with short and long branches)	1357:1396	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	3	27	theme	dielectric	397:406	arg1	constant					408:415	the dielectric constant	393:415	the dielectric constant of films that consisted of a wide range of microbial species	393:476	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
32010524	2	28	theme	intrinsic	316:324	arg1	constants					337:345	their intrinsic dielectric constants	310:345	their intrinsic dielectric constants in the THz frequency range	310:372	Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range.
32010524	9	29	with	α-glucan	1343:1350	arg1	branches					1388:1395	short and long branches	1373:1395	short and long branches	1373:1395	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	30	theme	cell	1418:1421	arg1	composition					1428:1438	cell wall composition	1418:1438	cell wall composition	1418:1438	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	30	theme	cell	1418:1421	arg1	cause					1453:1457	the main cause	1444:1457	the main cause of the observed differences in dielectric constants for different types of microorganisms	1444:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	6	31	from	measurements	865:876	arg1	environment					892:902	an aqueous environment	881:902	an aqueous environment using microfluidic metamaterials	881:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	9	32	from	cause	1453:1457	arg1	constants					1501:1509	dielectric constants	1490:1509	dielectric constants for different types of microorganisms	1490:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	3	33	theme	medium	552:557	arg1	theory					559:564	the effective medium theory	538:564	the effective medium theory	538:564	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
32010524	3	34	theme	microbial	460:468	arg1	species					470:476	microbial species	460:476	microbial species	460:476	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
32010524	9	35	theme	microorganisms	1534:1547	arg1	types					1525:1529	different types	1515:1529	different types of microorganisms	1515:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	36	theme	different	1515:1523	arg1	types					1525:1529	different types	1515:1529	different types of microorganisms	1515:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	6	37	theme	measurements	865:876	arg1	results					842:848	the results	838:848	the results of low-density measurements in an aqueous environment using microfluidic metamaterials	838:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	9	38	theme	dielectric	1490:1499	arg1	constants					1501:1509	dielectric constants	1490:1509	dielectric constants for different types of microorganisms	1490:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	3	39	theme	species	470:476	arg1	range					451:455	a wide range	444:455	a wide range of microbial species	444:476	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
32010524	3	40	theme	films	420:424	arg1	constant					408:415	the dielectric constant	393:415	the dielectric constant of films that consisted of a wide range of microbial species	393:476	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
32010524	7	41	theme	higher	1052:1057	arg1	contrast					1059:1066	higher contrast	1052:1066	higher contrast relative to bacteria	1052:1087	In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment.
32010524	6	42	theme	low-density	853:863	arg1	measurements					865:876	low-density measurements	853:876	low-density measurements in an aqueous environment using microfluidic metamaterials	853:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	0	43	theme	microorganisms	31:44	arg1	types					22:26	different types	12:26	different types of microorganisms with terahertz spectroscopy	12:72	Identifying different types of microorganisms with terahertz spectroscopy.
32010524	5	44	theme	high	715:718	arg1	constants					731:739	particularly high dielectric constants	702:739	particularly high dielectric constants	702:739	The yeasts exhibited particularly high dielectric constants reaching 5.63-5.97, which were even higher than that of water.
32010524	7	45	from	shift	960:964	arg1	resonance					986:994	the metamaterial resonance	969:994	the metamaterial resonance	969:994	In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment.
32010524	8	46	theme	yeasts	1152:1157	arg1	deposition					1134:1143	the deposition	1130:1143	the deposition of the yeasts	1130:1157	By contrast, the deposition of the yeasts induced a red shift because their dielectric constant was higher than that of water.
32010524	8	47	theme	dielectric	1193:1202	arg1	constant					1204:1211	their dielectric constant	1187:1211	their dielectric constant	1187:1211	By contrast, the deposition of the yeasts induced a red shift because their dielectric constant was higher than that of water.
32010524	2	48	theme	THz	354:356	arg1	range					368:372	the THz frequency range	350:372	the THz frequency range	350:372	Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range.
32010524	0	49	theme	terahertz	51:59	arg1	spectroscopy					61:72	terahertz spectroscopy	51:72	terahertz spectroscopy	51:72	Identifying different types of microorganisms with terahertz spectroscopy.
32010524	6	50	from	results	842:848	arg1	environment					892:902	an aqueous environment	881:902	an aqueous environment using microfluidic metamaterials	881:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	1	51	theme	fluorescent	141:151	arg1	labeling					153:160	fluorescent labeling	141:160	fluorescent labeling	141:160	Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes.
32010524	9	52	with	β-glucans	1357:1365	arg1	branches					1388:1395	short and long branches	1373:1395	short and long branches	1373:1395	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	8	53	theme	red	1169:1171	arg1	shift					1173:1177	a red shift	1167:1177	a red shift	1167:1177	By contrast, the deposition of the yeasts induced a red shift because their dielectric constant was higher than that of water.
32010524	1	54	theme	cultivation	166:176	arg1	processes					178:186	cultivation processes	166:186	cultivation processes	166:186	Most microbial detection techniques require pretreatment, such as fluorescent labeling and cultivation processes.
32010524	4	55	theme	molds	598:602	arg1	1.24-1.85					608:616	1.24-1.85	608:616	1.24-1.85	608:616	The dielectric constant of the molds was 1.24-1.85, which was lower than that of bacteria ranging from 2.75-4.11.
32010524	4	55	theme	molds	598:602	arg1	constant					582:589	The dielectric constant	567:589	The dielectric constant of the molds	567:602	The dielectric constant of the molds was 1.24-1.85, which was lower than that of bacteria ranging from 2.75-4.11.
32010524	2	56	theme	novel	206:210	arg1	tools					212:216	novel tools	206:216	novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range	206:372	Here, we propose novel tools for classifying and identifying microorganisms such as molds, yeasts, and bacteria based on their intrinsic dielectric constants in the THz frequency range.
32010524	6	57	with	consistent	822:831	arg1	results					842:848	the results	838:848	the results of low-density measurements in an aqueous environment using microfluidic metamaterials	838:935	These values were consistent with the results of low-density measurements in an aqueous environment using microfluidic metamaterials.
32010524	9	58	theme	observed	1466:1473	arg1	differences					1475:1485	the observed differences	1462:1485	the observed differences in dielectric constants for different types of microorganisms	1462:1547	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	59	theme	short	1373:1377	arg1	branches					1388:1395	short and long branches	1373:1395	short and long branches	1373:1395	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	60	theme	dielectric	1269:1278	arg1	chitin					1335:1340	chitin	1335:1340	chitin	1335:1340	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	60	theme	dielectric	1269:1278	arg1	constants					1280:1288	the dielectric constants	1265:1288	the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches)	1265:1396	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	60	theme	dielectric	1269:1278	arg1	α-glucan					1343:1350	α-glucan	1343:1350	α-glucan	1343:1350	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	9	60	theme	dielectric	1269:1278	arg1	β-glucans					1357:1365	β-glucans	1357:1365	β-glucans (with short and long branches)	1357:1396	Finally, we measured the dielectric constants of peptidoglycan and polysaccharides such as chitin, α-glucan, and β-glucans (with short and long branches), and confirmed that cell wall composition was the main cause of the observed differences in dielectric constants for different types of microorganisms.
32010524	7	61	theme	metamaterial	973:984	arg1	resonance					986:994	the metamaterial resonance	969:994	the metamaterial resonance	969:994	In particular, a blue shift in the metamaterial resonance occurred for molds and bacteria, whereas the molds have higher contrast relative to bacteria in the aqueous environment.
32010524	3	62	theme	individual	512:521	arg1	microbes					523:530	the individual microbes	508:530	the individual microbes using the effective medium theory	508:564	We first measured the dielectric constant of films that consisted of a wide range of microbial species, and extracted the values for the individual microbes using the effective medium theory.
31017130	9	0	from	localization	1597:1608	arg1	domain					1666:1671	time-frequency domain	1651:1671	time-frequency domain	1651:1671	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	9	0	from	localization	1597:1608	arg1	space					1638:1642	space	1638:1642	space	1638:1642	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	1	1	theme	embedded	156:163	arg1	bacteria					147:154	bacteria	147:154	bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	147:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	2	theme	polysaccharides	247:261	arg1	composition					232:242	a complex composition	222:242	a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	222:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	0	3	theme	cells	85:89	arg1	properties					51:60	mechanical properties	40:60	mechanical properties of biofilms and single cells	40:89	Acquisition of time-frequency localized mechanical properties of biofilms and single cells with high spatial resolution.
31017130	3	4	theme	high	674:677	arg1	resolution					687:696	a high spatial resolution	672:696	a high spatial resolution	672:696	However, it is challenging yet important to investigate mechanical behaviors of biofilms with a high spatial resolution because biofilms are very heterogeneous.
31017130	9	5	theme	biofilm	1717:1723	arg1	stability					1725:1733	biofilm stability	1717:1733	biofilm stability	1717:1733	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	1	6	from	embedded	156:163	arg1	substances					192:201	extracellular polymeric substances	168:201	extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	168:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	6	from	embedded	156:163	arg1	EPS					204:206	EPS	204:206	EPS	204:206	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	2	7	theme	biofilms	343:350	arg1	properties					325:334	Desirable mechanical properties	304:334	Desirable mechanical properties of the biofilms	304:350	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	5	8	theme	wide	1084:1087	arg1	window					1104:1109	a wide time-frequency window	1082:1109	a wide time-frequency window	1082:1109	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	0	9	theme	spatial	101:107	arg1	resolution					109:118	high spatial resolution	96:118	high spatial resolution	96:118	Acquisition of time-frequency localized mechanical properties of biofilms and single cells with high spatial resolution.
31017130	3	10	theme	spatial	679:685	arg1	resolution					687:696	a high spatial resolution	672:696	a high spatial resolution	672:696	However, it is challenging yet important to investigate mechanical behaviors of biofilms with a high spatial resolution because biofilms are very heterogeneous.
31017130	9	11	theme	stability	1725:1733	arg1	understanding					1700:1712	the understanding	1696:1712	the understanding of biofilm stability, cohesiveness, dispersal, and control	1696:1771	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	6	12	theme	intensive	1239:1247	arg1	amount					1249:1254	the intensive amount	1235:1254	the intensive amount of time-dependent information experimentally available that has been largely overlooked	1235:1342	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	6	12	theme	intensive	1239:1247	arg1	information					1274:1284	time-dependent information	1259:1284	time-dependent information experimentally available	1259:1309	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	7	13	theme	single-cell	1451:1461	arg1	level					1463:1467	the single-cell level	1447:1467	the single-cell level	1447:1467	It is shown that this technique provides a detailed nanorheological signature of the biofilms even at the single-cell level.
31017130	1	14	theme	proteins	264:271	arg1	composition					232:242	a complex composition	222:242	a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	222:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	0	15	theme	high	96:99	arg1	resolution					109:118	high spatial resolution	96:118	high spatial resolution	96:118	Acquisition of time-frequency localized mechanical properties of biofilms and single cells with high spatial resolution.
31017130	6	16	theme	spectroscopy	1150:1161	arg1	use					1130:1132	the use	1126:1132	the use of static force spectroscopy in combination with an appropriate viscoelastic framework	1126:1219	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	9	17	theme	cohesiveness	1736:1747	arg1	understanding					1700:1712	the understanding	1696:1712	the understanding of biofilm stability, cohesiveness, dispersal, and control	1696:1771	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	6	18	theme	viscoelastic	1198:1209	arg1	framework					1211:1219	an appropriate viscoelastic framework	1183:1219	an appropriate viscoelastic framework	1183:1219	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	7	19	theme	detailed	1388:1395	arg1	signature					1413:1421	a detailed nanorheological signature	1386:1421	a detailed nanorheological signature of the biofilms	1386:1437	It is shown that this technique provides a detailed nanorheological signature of the biofilms even at the single-cell level.
31017130	1	20	theme	extracellular	168:180	arg1	substances					192:201	extracellular polymeric substances	168:201	extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	168:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	20	theme	extracellular	168:180	arg1	EPS					204:206	EPS	204:206	EPS	204:206	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	5	21	theme	atomic	934:939	arg1	microscope					947:956	an atomic force microscope	931:956	an atomic force microscope (AFM)	931:962	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	5	21	theme	atomic	934:939	arg1	AFM					959:961	AFM	959:961	AFM	959:961	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	1	22	theme	polymeric	182:190	arg1	substances					192:201	extracellular polymeric substances	168:201	extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	168:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	22	theme	polymeric	182:190	arg1	EPS					204:206	EPS	204:206	EPS	204:206	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	2	23	theme	treatment	468:476	arg1	conditions					478:487	different treatment conditions	458:487	different treatment conditions	458:487	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	6	24	theme	available	1301:1309	arg1	information					1274:1284	time-dependent information	1259:1284	time-dependent information experimentally available	1259:1309	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	9	25	theme	mechanical	1613:1622	arg1	properties					1624:1633	mechanical properties	1613:1633	mechanical properties	1613:1633	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	2	26	theme	Desirable	304:312	arg1	properties					325:334	Desirable mechanical properties	304:334	Desirable mechanical properties of the biofilms	304:350	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	8	27	theme	raw	1574:1576	arg1	data					1578:1581	experimental raw data	1561:1581	experimental raw data	1561:1581	We share the computational routines that would allow any user to perform the analysis from experimental raw data.
31017130	5	28	theme	powerful	867:874	arg1	technique					876:884	a powerful technique	865:884	a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window	865:1109	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	8	29	theme	experimental	1561:1572	arg1	data					1578:1581	experimental raw data	1561:1581	experimental raw data	1561:1581	We share the computational routines that would allow any user to perform the analysis from experimental raw data.
31017130	5	30	theme	force	941:945	arg1	microscope					947:956	an atomic force microscope	931:956	an atomic force microscope (AFM)	931:962	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	5	30	theme	force	941:945	arg1	AFM					959:961	AFM	959:961	AFM	959:961	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	9	31	theme	dispersal	1750:1758	arg1	understanding					1700:1712	the understanding	1696:1712	the understanding of biofilm stability, cohesiveness, dispersal, and control	1696:1771	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	1	32	theme	extracellular	278:290	arg1	DNA					292:294	extracellular DNA	278:294	extracellular DNA (eDNA)	278:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	32	theme	extracellular	278:290	arg1	eDNA					297:300	eDNA	297:300	eDNA	297:300	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	7	33	theme	biofilms	1430:1437	arg1	signature					1413:1421	a detailed nanorheological signature	1386:1421	a detailed nanorheological signature of the biofilms	1386:1437	It is shown that this technique provides a detailed nanorheological signature of the biofilms even at the single-cell level.
31017130	5	34	theme	biofilm	1056:1062	arg1	properties					1064:1073	highly spatial-localized biofilm properties	1031:1073	highly spatial-localized biofilm properties	1031:1073	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	0	35	theme	time-frequency	15:28	arg1	Acquisition					0:10	Acquisition	0:10	Acquisition of time-frequency	0:28	Acquisition of time-frequency localized mechanical properties of biofilms and single cells with high spatial resolution.
31017130	1	36	theme	DNA	292:294	arg1	composition					232:242	a complex composition	222:242	a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	222:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	9	37	theme	control	1765:1771	arg1	understanding					1700:1712	the understanding	1696:1712	the understanding of biofilm stability, cohesiveness, dispersal, and control	1696:1771	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	3	38	theme	mechanical	634:643	arg1	behaviors					645:653	mechanical behaviors	634:653	mechanical behaviors of biofilms	634:665	However, it is challenging yet important to investigate mechanical behaviors of biofilms with a high spatial resolution because biofilms are very heterogeneous.
31017130	5	39	theme	high	904:907	arg1	resolution					917:926	the high spatial resolution	900:926	the high spatial resolution of an atomic force microscope (AFM)	900:962	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	8	40	theme	computational	1483:1495	arg1	routines					1497:1504	the computational routines	1479:1504	the computational routines that would allow any user to perform the analysis from experimental raw data	1479:1581	We share the computational routines that would allow any user to perform the analysis from experimental raw data.
31017130	2	41	theme	different	458:466	arg1	conditions					478:487	different treatment conditions	458:487	different treatment conditions	458:487	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	9	42	theme	properties	1624:1633	arg1	localization					1597:1608	The detailed localization	1584:1608	The detailed localization of mechanical properties in space and in time-frequency domain	1584:1671	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	5	43	theme	time-frequency	1089:1102	arg1	window					1104:1109	a wide time-frequency window	1082:1109	a wide time-frequency window	1082:1109	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	6	44	theme	information	1274:1284	arg1	amount					1249:1254	the intensive amount	1235:1254	the intensive amount of time-dependent information experimentally available that has been largely overlooked	1235:1342	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	6	44	theme	information	1274:1284	arg1	information					1274:1284	time-dependent information	1259:1284	time-dependent information experimentally available	1259:1309	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	0	45	theme	mechanical	40:49	arg1	properties					51:60	mechanical properties	40:60	mechanical properties of biofilms and single cells	40:89	Acquisition of time-frequency localized mechanical properties of biofilms and single cells with high spatial resolution.
31017130	6	46	with	combination	1166:1176	arg1	framework					1211:1219	an appropriate viscoelastic framework	1183:1219	an appropriate viscoelastic framework	1183:1219	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	6	47	theme	time-dependent	1259:1272	arg1	information					1274:1284	time-dependent information	1259:1284	time-dependent information experimentally available	1259:1309	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	2	48	theme	properties	444:453	arg1	response					421:428	the response	417:428	the response of mechanical properties to different treatment conditions	417:487	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	5	49	theme	spatial	909:915	arg1	resolution					917:926	the high spatial resolution	900:926	the high spatial resolution of an atomic force microscope (AFM)	900:962	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	2	50	theme	mechanical	433:442	arg1	properties					444:453	mechanical properties	433:453	mechanical properties	433:453	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	8	51	from	data	1578:1581	arg1	analysis					1547:1554	the analysis	1543:1554	the analysis from experimental raw data	1543:1581	We share the computational routines that would allow any user to perform the analysis from experimental raw data.
31017130	2	52	theme	engineering	556:566	arg1	surfaces					568:575	engineering surfaces	556:575	engineering surfaces	556:575	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	1	53	contain	contain	214:220	arg1	substances					192:201	extracellular polymeric substances	168:201	extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	168:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	53	contain	contain	214:220	arg1	EPS					204:206	EPS	204:206	EPS	204:206	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	53	contain	contain	214:220	arg2	composition					232:242	a complex composition	222:242	a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	222:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	5	54	theme	spatial-localized	1038:1054	arg1	properties					1064:1073	highly spatial-localized biofilm properties	1031:1073	highly spatial-localized biofilm properties	1031:1073	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	6	55	theme	force	1144:1148	arg1	spectroscopy					1150:1161	static force spectroscopy	1137:1161	static force spectroscopy	1137:1161	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	7	56	theme	nanorheological	1397:1411	arg1	signature					1413:1421	a detailed nanorheological signature	1386:1421	a detailed nanorheological signature of the biofilms	1386:1437	It is shown that this technique provides a detailed nanorheological signature of the biofilms even at the single-cell level.
31017130	5	57	theme	rigorous	971:978	arg1	analysis					1011:1018	a rigorous history-dependent viscoelastic analysis	969:1018	a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window	969:1109	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	4	58	theme	time-dependent	786:799	arg1	behavior					812:819	their time-dependent mechanical behavior	780:819	their time-dependent mechanical behavior	780:819	Moreover, biofilms are viscoelastic, and their time-dependent mechanical behavior is difficult to capture.
31017130	9	59	theme	time-frequency	1651:1664	arg1	domain					1666:1671	time-frequency domain	1651:1671	time-frequency domain	1651:1671	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	6	60	theme	static	1137:1142	arg1	spectroscopy					1150:1161	static force spectroscopy	1137:1161	static force spectroscopy	1137:1161	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	5	61	theme	microscope	947:956	arg1	resolution					917:926	the high spatial resolution	900:926	the high spatial resolution of an atomic force microscope (AFM)	900:962	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	6	62	theme	appropriate	1186:1196	arg1	framework					1211:1219	an appropriate viscoelastic framework	1183:1219	an appropriate viscoelastic framework	1183:1219	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	9	63	theme	detailed	1588:1595	arg1	localization					1597:1608	The detailed localization	1584:1608	The detailed localization of mechanical properties in space and in time-frequency domain	1584:1671	The detailed localization of mechanical properties in space and in time-frequency domain provides insights into the understanding of biofilm stability, cohesiveness, dispersal, and control.
31017130	5	64	theme	history-dependent	980:996	arg1	analysis					1011:1018	a rigorous history-dependent viscoelastic analysis	969:1018	a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window	969:1109	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	1	65	from	substances	192:201	arg1	embedded					156:163	embedded	156:163	embedded	156:163	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	2	66	theme	mechanical	314:323	arg1	properties					325:334	Desirable mechanical properties	304:334	Desirable mechanical properties of the biofilms	304:350	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
31017130	1	67	theme	complex	224:230	arg1	composition					232:242	a complex composition	222:242	a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	222:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	0	68	theme	single	78:83	arg1	cells					85:89	single cells	78:89	single cells	78:89	Acquisition of time-frequency localized mechanical properties of biofilms and single cells with high spatial resolution.
31017130	3	69	theme	biofilms	658:665	arg1	behaviors					645:653	mechanical behaviors	634:653	mechanical behaviors of biofilms	634:665	However, it is challenging yet important to investigate mechanical behaviors of biofilms with a high spatial resolution because biofilms are very heterogeneous.
31017130	5	70	theme	viscoelastic	998:1009	arg1	analysis					1011:1018	a rigorous history-dependent viscoelastic analysis	969:1018	a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window	969:1109	Herein, we develop a powerful technique that combines the high spatial resolution of an atomic force microscope (AFM) with a rigorous history-dependent viscoelastic analysis to deliver highly spatial-localized biofilm properties within a wide time-frequency window.
31017130	0	71	theme	biofilms	65:72	arg1	properties					51:60	mechanical properties	40:60	mechanical properties of biofilms and single cells	40:89	Acquisition of time-frequency localized mechanical properties of biofilms and single cells with high spatial resolution.
31017130	4	72	theme	mechanical	801:810	arg1	behavior					812:819	their time-dependent mechanical behavior	780:819	their time-dependent mechanical behavior	780:819	Moreover, biofilms are viscoelastic, and their time-dependent mechanical behavior is difficult to capture.
31017130	6	73	from	use	1130:1132	arg1	combination					1166:1176	combination	1166:1176	combination with an appropriate viscoelastic framework	1166:1219	By exploiting the use of static force spectroscopy in combination with an appropriate viscoelastic framework, we highlight the intensive amount of time-dependent information experimentally available that has been largely overlooked.
31017130	1	74	theme	bacteria	147:154	arg1	Biofilms					121:128	Biofilms	121:128	Biofilms	121:128	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	1	74	theme	bacteria	147:154	arg1	cluster					136:142	a cluster	134:142	a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA)	134:301	Biofilms are a cluster of bacteria embedded in extracellular polymeric substances (EPS) that contain a complex composition of polysaccharides, proteins, and extracellular DNA (eDNA).
31017130	2	75	theme	biofilm	509:515	arg1	control					517:523	biofilm control	509:523	biofilm control	509:523	Desirable mechanical properties of the biofilms are critical for their survival, propagation, and dispersal, and the response of mechanical properties to different treatment conditions also sheds light on biofilm control and eradication in vivo and on engineering surfaces.
29515825	0	0	theme	-O-linked	46:54	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	4	1	theme	cell	490:493	arg1	lines					495:499	tumour cell lines	483:499	tumour cell lines	483:499	The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.
29515825	0	2	theme	norcantharidin	69:82	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	4	3	theme	tumour	483:488	arg1	lines					495:499	tumour cell lines	483:499	tumour cell lines	483:499	The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.
29515825	0	4	theme	camptothecin	56:67	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	4	5	theme	solubility	443:452	arg1	activity					466:473	better solubility and similar activity	436:473	better solubility and similar activity against tumour cell lines	436:499	The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.
29515825	4	6	theme	new	385:387	arg1	compound					399:406	The new synthetic compound I	381:408	The new synthetic compound I	381:408	The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.
29515825	0	7	theme	ester	89:93	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	0	8	theme	acid	84:87	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	4	9	theme	similar	458:464	arg1	activity					466:473	better solubility and similar activity	436:473	better solubility and similar activity against tumour cell lines	436:499	The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.
29515825	0	10	theme	simple	2:7	arg1	route					9:13	A simple route	0:13	A simple route	0:13	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	3	11	theme	high	309:312	arg1	yield					314:318	high yield	309:318	high yield	309:318	This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues.
29515825	1	12	theme	novel	153:157	arg1	derivative					213:222	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	1	13	theme	acid-sensitive	159:172	arg1	derivative					213:222	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	1	14	theme	camptothecin	174:185	arg1	derivative					213:222	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	1	15	theme	norcantharidin	187:200	arg1	derivative					213:222	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	0	16	theme	novel	20:24	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	1	17	theme	acid	202:205	arg1	derivative					213:222	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	0	18	link	-O-linked	46:54	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	1	19	theme	ester	207:211	arg1	derivative					213:222	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	a novel acid-sensitive camptothecin norcantharidin acid ester derivative I	151:224	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	3	20	theme	analogues	370:378	arg1	synthesis					357:365	the synthesis	353:365	the synthesis of analogues	353:378	This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues.
29515825	3	21	theme	working	331:337	arg1	procedure					339:347	simple working procedure	324:347	simple working procedure for the synthesis of analogues	324:378	This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues.
29515825	3	22	theme	several	279:285	arg1	procedure					339:347	simple working procedure	324:347	simple working procedure for the synthesis of analogues	324:378	This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues.
29515825	3	22	theme	several	279:285	arg1	yield					314:318	high yield	309:318	high yield	309:318	This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues.
29515825	3	22	theme	several	279:285	arg1	advantages					287:296	several advantages	279:296	several advantages	279:296	This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues.
29515825	0	23	theme	acid-sensitive	26:39	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	3	24	theme	simple	324:329	arg1	procedure					339:347	simple working procedure	324:347	simple working procedure for the synthesis of analogues	324:378	This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues.
29515825	4	25	theme	synthetic	389:397	arg1	compound					399:406	The new synthetic compound I	381:408	The new synthetic compound I	381:408	The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.
29515825	0	26	dep	route	9:13	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	1	27	theme	facile	109:114	arg1	method					126:131	A facile synthetic method	107:131	A facile synthetic method	107:131	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	0	28	theme	S	44:44	arg1	derivative					95:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative	18:104	A simple route to a novel acid-sensitive 20(S)-O-linked camptothecin norcantharidin acid ester derivative.
29515825	1	29	theme	synthetic	116:124	arg1	method					126:131	A facile synthetic method	107:131	A facile synthetic method	107:131	A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I.
29515825	2	30	theme	total	231:235	arg1	yield					237:241	The total yield	227:241	The total yield	227:241	The total yield can reach 71%.
31152018	7	0	theme	hydrolytic	1132:1141	arg1	potential					1143:1151	the community hydrolytic potential	1118:1151	the community hydrolytic potential	1118:1151	The results confirm the retention of the community hydrolytic potential during acidosis and indicate Bacteroidetes to be largely involved in biomass degradation.
31152018	3	1	theme	community	495:503	arg1	redundancy					516:525	the community functional redundancy	491:525	the community functional redundancy	491:525	This suggests the retention of the community functional redundancy during the process failure.
31152018	9	2	theme	analyses	1463:1470	arg1	combination					1434:1444	The combination	1430:1444	The combination of bioinformatic analyses and activity tests	1430:1489	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	9	3	theme	activity	1476:1483	arg1	tests					1485:1489	activity tests	1476:1489	activity tests	1476:1489	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	14	4	theme	biomass	2645:2651	arg1	pretreatment					2653:2664	biomass pretreatment	2645:2664	biomass pretreatment	2645:2664	Using naturally evolved cocktails of enzymes for biomass pretreatment could be an interesting alternative to the commonly used chemical pretreatments.
31152018	11	5	theme	digestion	2125:2133	arg1	systems					2135:2141	some anaerobic digestion systems	2110:2141	some anaerobic digestion systems	2110:2141	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	14	6	theme	enzymes	2633:2639	arg1	cocktails					2620:2628	naturally evolved cocktails	2602:2628	naturally evolved cocktails of enzymes for biomass pretreatment	2602:2664	Using naturally evolved cocktails of enzymes for biomass pretreatment could be an interesting alternative to the commonly used chemical pretreatments.
31152018	4	7	theme	hydrolytic	672:681	arg1	potential					683:691	the carbohydrate hydrolytic potential	655:691	the carbohydrate hydrolytic potential of the microbial community	655:718	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	2	8	theme	microbial	311:319	arg1	communities					321:331	microbial communities	311:331	microbial communities	311:331	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	5	9	theme	key	877:879	arg1	microbes					881:888	key microbes	877:888	key microbes	877:888	To that purpose, carbohydrate-active enzymes were identified, and to further link the community hydrolytic potential with key microbes, bacterial genomes were reconstructed.
31152018	9	10	theme	tests	1485:1489	arg1	combination					1434:1444	The combination	1430:1444	The combination of bioinformatic analyses and activity tests	1430:1489	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	4	11	theme	analyses	629:636	arg1	use					579:581	the use	575:581	the use of metagenomics and downstream bioinformatics analyses	575:636	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	13	12	dep	model	2415:2419	arg1	substrate					2528:2536	a common substrate	2519:2536	a common substrate for many industries, including pulp and paper production	2519:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	13	12	dep	model	2415:2419	arg1	biomass					2508:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	10	13	theme	functional	1853:1862	arg1	redundancy					1864:1873	its hydrolytic functional redundancy	1838:1873	its hydrolytic functional redundancy	1838:1873	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	13	14	theme	Bacteroidetes	2462:2474	arg1	substrate					2528:2536	a common substrate	2519:2536	a common substrate for many industries, including pulp and paper production	2519:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	13	14	theme	Bacteroidetes	2462:2474	arg1	biomass					2508:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	4	15	theme	community	710:718	arg1	potential					683:691	the carbohydrate hydrolytic potential	655:691	the carbohydrate hydrolytic potential of the microbial community	655:718	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	8	16	theme	hydrolytic	1317:1326	arg1	enzymes					1328:1334	carbohydrate hydrolytic enzymes	1304:1334	carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors	1304:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	1	17	theme	reactors	221:228	arg1	production					252:261	decreased methane production	234:261	decreased methane production	234:261	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	1	17	theme	reactors	221:228	arg1	acidosis					199:206	acidosis	199:206	acidosis of anaerobic reactors	199:228	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	10	18	theme	severe	1887:1892	arg1	acidosis					1894:1901	severe acidosis	1887:1901	severe acidosis	1887:1901	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	9	19	theme	glucomannan	1535:1545	arg1	degradation					1547:1557	acetylated glucomannan degradation	1524:1557	acetylated glucomannan degradation	1524:1557	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	10	20	theme	hydrolytic	1842:1851	arg1	redundancy					1864:1873	its hydrolytic functional redundancy	1838:1873	its hydrolytic functional redundancy	1838:1873	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	1	21	theme	Increased	137:145	arg1	hydrolysis					147:156	Increased hydrolysis	137:156	Increased hydrolysis of easily digestible biomass	137:185	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	13	22	theme	glucomannan	2435:2445	arg1	degradation					2447:2457	acetylated glucomannan degradation	2424:2457	acetylated glucomannan degradation	2424:2457	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	6	23	dep	specificity	977:987	arg1	the					973:975	the	973:975	the	973:975	In addition, we characterized biochemically the specificity and activity of selected enzymes, thus verifying the accuracy of the in silico predictions.
31152018	0	24	theme	Digestion	65:73	arg1	Microbiome					75:84	an Anaerobic Digestion Microbiome	52:84	an Anaerobic Digestion Microbiome	52:84	Carbohydrate Hydrolytic Potential and Redundancy of an Anaerobic Digestion Microbiome Exposed to Acidosis, as Uncovered by Metagenomics.
31152018	11	25	theme	phylum	2100:2105	arg1	abundance					2082:2090	the abundance	2078:2090	the abundance of this phylum in some anaerobic digestion systems	2078:2141	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	4	26	theme	microbial	700:708	arg1	community					710:718	the microbial community	696:718	the microbial community	696:718	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	1	27	theme	digestible	168:177	arg1	biomass					179:185	easily digestible biomass	161:185	easily digestible biomass	161:185	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	6	28	theme	selected	1005:1012	arg1	enzymes					1014:1020	selected enzymes	1005:1020	selected enzymes	1005:1020	In addition, we characterized biochemically the specificity and activity of selected enzymes, thus verifying the accuracy of the in silico predictions.
31152018	7	29	theme	biomass	1222:1228	arg1	degradation					1230:1240	biomass degradation	1222:1240	biomass degradation	1222:1240	The results confirm the retention of the community hydrolytic potential during acidosis and indicate Bacteroidetes to be largely involved in biomass degradation.
31152018	13	30	theme	acetylated	2424:2433	arg1	degradation					2447:2457	acetylated glucomannan degradation	2424:2457	acetylated glucomannan degradation	2424:2457	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	9	31	theme	lignocellulosic	1614:1628	arg1	biomass					1630:1636	lignocellulosic biomass	1614:1636	lignocellulosic biomass	1614:1636	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	13	32	theme	degradation	2447:2457	arg1	model					2415:2419	the model	2411:2419	the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production	2411:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	6	33	dep	in	1058:1059	arg1	silico					1061:1066	silico	1061:1066	silico	1061:1066	In addition, we characterized biochemically the specificity and activity of selected enzymes, thus verifying the accuracy of the in silico predictions.
31152018	0	34	theme	Carbohydrate	0:11	arg1	Potential					24:32	Carbohydrate Hydrolytic Potential	0:32	Carbohydrate Hydrolytic Potential	0:32	Carbohydrate Hydrolytic Potential and Redundancy of an Anaerobic Digestion Microbiome Exposed to Acidosis, as Uncovered by Metagenomics.
31152018	4	35	from	focus	736:740	arg1	acidosis					745:752	acidosis	745:752	acidosis	745:752	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	10	36	from	changes	1924:1930	arg1	composition					1945:1955	taxonomic composition	1935:1955	taxonomic composition	1935:1955	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	13	37	theme	various	2380:2386	arg1	biomasses					2388:2396	various biomasses	2380:2396	various biomasses	2380:2396	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	13	38	theme	Acetylated	2476:2485	arg1	substrate					2528:2536	a common substrate	2519:2536	a common substrate for many industries, including pulp and paper production	2519:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	13	38	theme	Acetylated	2476:2485	arg1	biomass					2508:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	11	39	theme	hydrolytic	2038:2047	arg1	diversity					2054:2062	Bacteroidetes hydrolytic gene diversity	2024:2062	Bacteroidetes hydrolytic gene diversity	2024:2062	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	5	40	theme	hydrolytic	851:860	arg1	potential					862:870	the community hydrolytic potential	837:870	the community hydrolytic potential with key microbes	837:888	To that purpose, carbohydrate-active enzymes were identified, and to further link the community hydrolytic potential with key microbes, bacterial genomes were reconstructed.
31152018	5	41	theme	carbohydrate-active	772:790	arg1	enzymes					792:798	carbohydrate-active enzymes	772:798	carbohydrate-active enzymes	772:798	To that purpose, carbohydrate-active enzymes were identified, and to further link the community hydrolytic potential with key microbes, bacterial genomes were reconstructed.
31152018	14	42	theme	chemical	2723:2730	arg1	pretreatments					2732:2744	the commonly used chemical pretreatments	2705:2744	the commonly used chemical pretreatments	2705:2744	Using naturally evolved cocktails of enzymes for biomass pretreatment could be an interesting alternative to the commonly used chemical pretreatments.
31152018	9	43	theme	enzymes	1692:1698	arg1	action					1662:1667	the action	1658:1667	the action of carbohydrate-active enzymes	1658:1698	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	10	44	theme	significant	1912:1922	arg1	changes					1924:1930	significant changes	1912:1930	significant changes in taxonomic composition	1912:1955	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	10	45	theme	digestion	1778:1786	arg1	experiment					1788:1797	the anaerobic digestion experiment	1764:1797	the anaerobic digestion experiment	1764:1797	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	10	46	from	stages	1754:1759	arg1	profiles					1728:1735	the gene profiles	1719:1735	the gene profiles at the different stages of the anaerobic digestion experiment	1719:1797	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	10	47	theme	different	1744:1752	arg1	stages					1754:1759	the different stages	1740:1759	the different stages of the anaerobic digestion experiment	1740:1797	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	9	48	dep	propose	1505:1511	arg1	driven					1648:1653	driven	1648:1653	is mainly driven by the action of carbohydrate-active enzymes	1638:1698	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	3	49	theme	functional	505:514	arg1	redundancy					516:525	the community functional redundancy	491:525	the community functional redundancy	491:525	This suggests the retention of the community functional redundancy during the process failure.
31152018	12	50	theme	hydrolytic	2248:2257	arg1	potential					2259:2267	the preserved hydrolytic potential	2234:2267	the preserved hydrolytic potential	2234:2267	Further, we observe genetic redundancy within the Bacteroidetes group, which accounts for the preserved hydrolytic potential during acidosis.
31152018	1	51	theme	methane	244:250	arg1	production					252:261	decreased methane production	234:261	decreased methane production	234:261	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	0	52	theme	Anaerobic	55:63	arg1	Microbiome					75:84	an Anaerobic Digestion Microbiome	52:84	an Anaerobic Digestion Microbiome	52:84	Carbohydrate Hydrolytic Potential and Redundancy of an Anaerobic Digestion Microbiome Exposed to Acidosis, as Uncovered by Metagenomics.
31152018	14	53	theme	interesting	2678:2688	arg1	alternative					2690:2700	an interesting alternative	2675:2700	an interesting alternative to the commonly used chemical pretreatments	2675:2744	Using naturally evolved cocktails of enzymes for biomass pretreatment could be an interesting alternative to the commonly used chemical pretreatments.
31152018	7	54	theme	community	1122:1130	arg1	potential					1143:1151	the community hydrolytic potential	1118:1151	the community hydrolytic potential	1118:1151	The results confirm the retention of the community hydrolytic potential during acidosis and indicate Bacteroidetes to be largely involved in biomass degradation.
31152018	11	55	theme	reconstructed	1971:1983	arg1	genomes					1995:2001	reconstructed bacterial genomes	1971:2001	reconstructed bacterial genomes	1971:2001	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	9	56	theme	bioinformatic	1449:1461	arg1	analyses					1463:1470	bioinformatic analyses	1449:1470	bioinformatic analyses	1449:1470	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	13	57	theme	pulp	2569:2572	arg1	production					2584:2593	pulp and paper production	2569:2593	pulp and paper production	2569:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	3	58	theme	process	538:544	arg1	failure					546:552	the process failure	534:552	the process failure	534:552	This suggests the retention of the community functional redundancy during the process failure.
31152018	9	59	theme	enzymatic	1590:1598	arg1	hydrolysis					1600:1609	The enzymatic hydrolysis	1586:1609	The enzymatic hydrolysis of lignocellulosic biomass	1586:1636	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	11	60	theme	anaerobic	2115:2123	arg1	systems					2135:2141	some anaerobic digestion systems	2110:2141	some anaerobic digestion systems	2110:2141	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	8	61	theme	genomic	1285:1291	arg1	content					1293:1299	genomic content	1285:1299	genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors	1285:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	1	62	theme	biomass	179:185	arg1	hydrolysis					147:156	Increased hydrolysis	137:156	Increased hydrolysis of easily digestible biomass	137:185	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	8	63	theme	higher	1264:1269	arg1	diversity					1271:1279	higher diversity	1264:1279	higher diversity	1264:1279	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	2	64	theme	communities	321:331	arg1	structure					298:306	the structure	294:306	the structure of microbial communities	294:331	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	4	65	theme	carbohydrate	659:670	arg1	potential					683:691	the carbohydrate hydrolytic potential	655:691	the carbohydrate hydrolytic potential of the microbial community	655:718	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	11	66	from	abundance	2082:2090	arg1	systems					2135:2141	some anaerobic digestion systems	2110:2141	some anaerobic digestion systems	2110:2141	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	4	67	theme	bioinformatics	614:627	arg1	analyses					629:636	downstream bioinformatics analyses	603:636	downstream bioinformatics analyses	603:636	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	13	68	theme	common	2521:2526	arg1	substrate					2528:2536	a common substrate	2519:2536	a common substrate for many industries, including pulp and paper production	2519:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	13	68	theme	common	2521:2526	arg1	biomass					2508:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	1	69	theme	anaerobic	211:219	arg1	reactors					221:228	anaerobic reactors	211:228	anaerobic reactors	211:228	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	8	70	theme	carbohydrate	1304:1315	arg1	enzymes					1328:1334	carbohydrate hydrolytic enzymes	1304:1334	carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors	1304:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	9	71	theme	acetylated	1524:1533	arg1	degradation					1547:1557	acetylated glucomannan degradation	1524:1557	acetylated glucomannan degradation	1524:1557	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	12	72	theme	Bacteroidetes	2194:2206	arg1	group					2208:2212	the Bacteroidetes group	2190:2212	the Bacteroidetes group	2190:2212	Further, we observe genetic redundancy within the Bacteroidetes group, which accounts for the preserved hydrolytic potential during acidosis.
31152018	8	73	theme	enzymes	1328:1334	arg1	diversity					1271:1279	higher diversity	1264:1279	higher diversity	1264:1279	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	8	73	theme	enzymes	1328:1334	arg1	content					1293:1299	genomic content	1285:1299	genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors	1285:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	13	74	theme	glucomannan-enriched	2487:2506	arg1	substrate					2528:2536	a common substrate	2519:2536	a common substrate for many industries, including pulp and paper production	2519:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	13	74	theme	glucomannan-enriched	2487:2506	arg1	biomass					2508:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	Bacteroidetes Acetylated glucomannan-enriched biomass	2462:2514	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	10	75	theme	taxonomic	1935:1943	arg1	composition					1945:1955	taxonomic composition	1935:1955	taxonomic composition	1935:1955	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	9	76	theme	degradation	1547:1557	arg1	model					1515:1519	a model	1513:1519	a model of acetylated glucomannan degradation	1513:1557	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	0	77	theme	Microbiome	75:84	arg1	Potential					24:32	Carbohydrate Hydrolytic Potential	0:32	Carbohydrate Hydrolytic Potential	0:32	Carbohydrate Hydrolytic Potential and Redundancy of an Anaerobic Digestion Microbiome Exposed to Acidosis, as Uncovered by Metagenomics.
31152018	0	77	theme	Microbiome	75:84	arg1	Redundancy					38:47	Redundancy	38:47	Redundancy	38:47	Carbohydrate Hydrolytic Potential and Redundancy of an Anaerobic Digestion Microbiome Exposed to Acidosis, as Uncovered by Metagenomics.
31152018	12	78	theme	genetic	2164:2170	arg1	redundancy					2172:2181	genetic redundancy	2164:2181	genetic redundancy	2164:2181	Further, we observe genetic redundancy within the Bacteroidetes group, which accounts for the preserved hydrolytic potential during acidosis.
31152018	11	79	theme	bacterial	1985:1993	arg1	genomes					1995:2001	reconstructed bacterial genomes	1971:2001	reconstructed bacterial genomes	1971:2001	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	5	80	theme	bacterial	891:899	arg1	genomes					901:907	bacterial genomes	891:907	bacterial genomes	891:907	To that purpose, carbohydrate-active enzymes were identified, and to further link the community hydrolytic potential with key microbes, bacterial genomes were reconstructed.
31152018	6	81	theme	enzymes	1014:1020	arg1	activity					993:1000	activity	993:1000	activity	993:1000	In addition, we characterized biochemically the specificity and activity of selected enzymes, thus verifying the accuracy of the in silico predictions.
31152018	6	81	theme	enzymes	1014:1020	arg1	specificity					977:987	specificity	977:987	specificity	977:987	In addition, we characterized biochemically the specificity and activity of selected enzymes, thus verifying the accuracy of the in silico predictions.
31152018	13	82	theme	polysaccharide	2314:2327	arg1	loci					2341:2344	new polysaccharide utilization loci	2310:2344	new polysaccharide utilization loci involved in the deconstruction of various biomasses	2310:2396	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	8	83	theme	phylum	1375:1380	arg1	dominance					1357:1365	the dominance	1353:1365	the dominance of this phylum over other bacteria in some anaerobic reactors	1353:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	2	84	dep	CO2	426:428	arg1	initially					416:424	initially	416:424	initially	416:424	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	9	85	theme	biomass	1630:1636	arg1	hydrolysis					1600:1609	The enzymatic hydrolysis	1586:1609	The enzymatic hydrolysis of lignocellulosic biomass	1586:1636	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	13	86	theme	new	2310:2312	arg1	loci					2341:2344	new polysaccharide utilization loci	2310:2344	new polysaccharide utilization loci involved in the deconstruction of various biomasses	2310:2396	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	8	87	theme	other	1387:1391	arg1	bacteria					1393:1400	other bacteria	1387:1400	other bacteria in some anaerobic reactors	1387:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	11	88	theme	Bacteroidetes	2024:2036	arg1	diversity					2054:2062	Bacteroidetes hydrolytic gene diversity	2024:2062	Bacteroidetes hydrolytic gene diversity	2024:2062	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	0	89	theme	Hydrolytic	13:22	arg1	Potential					24:32	Carbohydrate Hydrolytic Potential	0:32	Carbohydrate Hydrolytic Potential	0:32	Carbohydrate Hydrolytic Potential and Redundancy of an Anaerobic Digestion Microbiome Exposed to Acidosis, as Uncovered by Metagenomics.
31152018	13	90	theme	paper	2578:2582	arg1	production					2584:2593	pulp and paper production	2569:2593	pulp and paper production	2569:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	6	91	theme	predictions	1068:1078	arg1	accuracy					1042:1049	the accuracy	1038:1049	the accuracy of the in silico predictions	1038:1078	In addition, we characterized biochemically the specificity and activity of selected enzymes, thus verifying the accuracy of the in silico predictions.
31152018	4	92	theme	special	728:734	arg1	focus					736:740	a special focus	726:740	a special focus on acidosis	726:752	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	10	93	theme	gene	1723:1726	arg1	profiles					1728:1735	the gene profiles	1719:1735	the gene profiles at the different stages of the anaerobic digestion experiment	1719:1797	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	6	94	theme	in	1058:1059	arg1	predictions					1068:1078	the in silico predictions	1054:1078	the in silico predictions	1054:1078	In addition, we characterized biochemically the specificity and activity of selected enzymes, thus verifying the accuracy of the in silico predictions.
31152018	8	95	theme	anaerobic	1410:1418	arg1	reactors					1420:1427	some anaerobic reactors	1405:1427	some anaerobic reactors	1405:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	2	96	theme	biogas	408:413	arg1	production					431:440	biogas (initially CO2) production	408:440	biogas (initially CO2) production	408:440	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	13	97	theme	biomasses	2388:2396	arg1	deconstruction					2362:2375	the deconstruction	2358:2375	the deconstruction of various biomasses	2358:2396	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	12	98	theme	preserved	2238:2246	arg1	potential					2259:2267	the preserved hydrolytic potential	2234:2267	the preserved hydrolytic potential	2234:2267	Further, we observe genetic redundancy within the Bacteroidetes group, which accounts for the preserved hydrolytic potential during acidosis.
31152018	2	99	dep	optimal	399:405	arg1	conditions					376:385	the conditions	372:385	the conditions	372:385	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	2	99	dep	optimal	399:405	arg1	to					396:397	to	396:397	to	396:397	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	2	99	dep	optimal	399:405	arg1	optimal					399:405	optimal	399:405	optimal	399:405	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	11	100	theme	gene	2049:2052	arg1	diversity					2054:2062	Bacteroidetes hydrolytic gene diversity	2024:2062	Bacteroidetes hydrolytic gene diversity	2024:2062	By analyzing reconstructed bacterial genomes, we demonstrate that Bacteroidetes hydrolytic gene diversity likely favors the abundance of this phylum in some anaerobic digestion systems.
31152018	7	101	theme	potential	1143:1151	arg1	retention					1105:1113	the retention	1101:1113	the retention of the community hydrolytic potential during acidosis	1101:1167	The results confirm the retention of the community hydrolytic potential during acidosis and indicate Bacteroidetes to be largely involved in biomass degradation.
31152018	14	102	theme	used	2718:2721	arg1	pretreatments					2732:2744	the commonly used chemical pretreatments	2705:2744	the commonly used chemical pretreatments	2705:2744	Using naturally evolved cocktails of enzymes for biomass pretreatment could be an interesting alternative to the commonly used chemical pretreatments.
31152018	9	103	theme	carbohydrate-active	1672:1690	arg1	enzymes					1692:1698	carbohydrate-active enzymes	1672:1698	carbohydrate-active enzymes	1672:1698	The combination of bioinformatic analyses and activity tests enabled us to propose a model of acetylated glucomannan degradation by BacteroidetesIMPORTANCE The enzymatic hydrolysis of lignocellulosic biomass is mainly driven by the action of carbohydrate-active enzymes.
31152018	2	104	dep	biogas	408:413	arg1	CO2					426:428	CO2	426:428	CO2	426:428	Previously, it was shown that the structure of microbial communities changed during acidosis; however, once the conditions are back to optimal, biogas (initially CO2) production quickly restarts.
31152018	14	105	theme	evolved	2612:2618	arg1	cocktails					2620:2628	naturally evolved cocktails	2602:2628	naturally evolved cocktails of enzymes for biomass pretreatment	2602:2664	Using naturally evolved cocktails of enzymes for biomass pretreatment could be an interesting alternative to the commonly used chemical pretreatments.
31152018	10	106	theme	experiment	1788:1797	arg1	stages					1754:1759	the different stages	1740:1759	the different stages of the anaerobic digestion experiment	1740:1797	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	8	107	from	bacteria	1393:1400	arg1	reactors					1420:1427	some anaerobic reactors	1405:1427	some anaerobic reactors	1405:1427	Bacteroidetes showed higher diversity and genomic content of carbohydrate hydrolytic enzymes that might favor the dominance of this phylum over other bacteria in some anaerobic reactors.
31152018	4	108	theme	metagenomics	586:597	arg1	use					579:581	the use	575:581	the use of metagenomics and downstream bioinformatics analyses	575:636	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	5	109	with	potential	862:870	arg1	microbes					881:888	key microbes	877:888	key microbes	877:888	To that purpose, carbohydrate-active enzymes were identified, and to further link the community hydrolytic potential with key microbes, bacterial genomes were reconstructed.
31152018	10	110	theme	anaerobic	1768:1776	arg1	experiment					1788:1797	the anaerobic digestion experiment	1764:1797	the anaerobic digestion experiment	1764:1797	By characterizing the gene profiles at the different stages of the anaerobic digestion experiment, we showed that the microbiome retains its hydrolytic functional redundancy even during severe acidosis, despite significant changes in taxonomic composition.
31152018	1	111	theme	decreased	234:242	arg1	production					252:261	decreased methane production	234:261	decreased methane production	234:261	Increased hydrolysis of easily digestible biomass may lead to acidosis of anaerobic reactors and decreased methane production.
31152018	5	112	theme	community	841:849	arg1	potential					862:870	the community hydrolytic potential	837:870	the community hydrolytic potential with key microbes	837:888	To that purpose, carbohydrate-active enzymes were identified, and to further link the community hydrolytic potential with key microbes, bacterial genomes were reconstructed.
31152018	13	113	theme	many	2542:2545	arg1	industries					2547:2556	many industries	2542:2556	many industries	2542:2556	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	13	113	theme	many	2542:2545	arg1	production					2584:2593	pulp and paper production	2569:2593	pulp and paper production	2569:2593	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31152018	4	114	theme	downstream	603:612	arg1	analyses					629:636	downstream bioinformatics analyses	603:636	downstream bioinformatics analyses	603:636	In this study, with the use of metagenomics and downstream bioinformatics analyses, we characterize the carbohydrate hydrolytic potential of the microbial community, with a special focus on acidosis.
31152018	3	115	theme	redundancy	516:525	arg1	retention					478:486	the retention	474:486	the retention of the community functional redundancy during the process failure	474:552	This suggests the retention of the community functional redundancy during the process failure.
31152018	13	116	theme	utilization	2329:2339	arg1	loci					2341:2344	new polysaccharide utilization loci	2310:2344	new polysaccharide utilization loci involved in the deconstruction of various biomasses	2310:2396	This work also uncovers new polysaccharide utilization loci involved in the deconstruction of various biomasses and proposes the model of acetylated glucomannan degradation by Bacteroidetes Acetylated glucomannan-enriched biomass is a common substrate for many industries, including pulp and paper production.
31821772	11	0	theme	potential	1664:1672	arg1	outcome					1635:1641	this outcome	1630:1641	this outcome	1630:1641	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	11	0	theme	potential	1664:1672	arg1	strategy					1674:1681	a potential strategy	1662:1681	a potential strategy contributing to the management of dental caries	1662:1729	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	6	1	theme	glucose	827:833	arg1	metabolism					835:844	galactose and glucose metabolism	813:844	metabolism	835:844	In particular, overproducing ASvicR demonstrated a reduction in galactose and glucose metabolism by monosaccharide composition analysis.
31821772	3	2	theme	small	487:491	arg1	msRNAs					499:504	msRNAs	499:504	msRNAs	499:504	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	2	theme	small	487:491	arg1	RNAs					493:496	microRNA-size small RNAs	473:496	microRNA-size small RNAs (msRNAs)	473:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	12	3	theme	ASvicR-mediated	1790:1804	arg1	regulation					1813:1822	ASvicR-mediated sponge regulation	1790:1822	ASvicR-mediated sponge regulation	1790:1822	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	4	4	theme	impeded	565:571	arg1	growth					583:588	significantly impeded bacterial growth	551:588	significantly impeded bacterial growth	551:588	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	6	5	theme	galactose	813:821	arg1	metabolism					835:844	galactose and glucose metabolism	813:844	metabolism	835:844	In particular, overproducing ASvicR demonstrated a reduction in galactose and glucose metabolism by monosaccharide composition analysis.
31821772	12	6	theme	regulation	1813:1822	arg1	role					1782:1785	an important role	1769:1785	an important role of ASvicR-mediated sponge regulation in S. mutans	1769:1835	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	11	7	theme	caries	1613:1618	arg1	patients					1620:1627	early childhood caries patients	1597:1627	early childhood caries patients	1597:1627	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	11	8	theme	early	1597:1601	arg1	patients					1620:1627	early childhood caries patients	1597:1627	early childhood caries patients	1597:1627	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	2	9	theme	response	314:321	arg1	VicR					334:337	VicR	334:337	VicR	334:337	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	9	theme	response	314:321	arg1	regulator					323:331	a global and vital response regulator	295:331	a global and vital response regulator	295:331	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	9	10	theme	rnc-related	1216:1226	arg1	RNA					1238:1240	an rnc-related messenger RNA	1213:1240	an rnc-related messenger RNA	1213:1240	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	9	10	theme	rnc-related	1216:1226	arg1	msRNA1657					1193:1201	putative msRNA1657	1184:1201	putative msRNA1657	1184:1201	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	5	11	theme	ASvicR	696:701	arg1	RNA					703:705	the ASvicR RNA	692:705	the ASvicR RNA	692:705	Transcriptome analysis revealed that the ASvicR RNA mainly regulated carbohydrate metabolism.
31821772	11	12	theme	mutans	1507:1512	arg1	strains					1514:1520	clinical S. mutans strains	1495:1520	clinical S. mutans strains from caries-free children	1495:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	13	13	theme	bacterial	2024:2032	arg1	regulation					2039:2048	bacterial gene regulation	2024:2048	bacterial gene regulation	2024:2048	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	4	14	dep	overexpression	536:549	arg1	growth					583:588	significantly impeded bacterial growth	551:588	significantly impeded bacterial growth	551:588	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	4	14	dep	overexpression	536:549	arg1	synthesis					617:625	biofilm exopolysaccharide synthesis	591:625	biofilm exopolysaccharide synthesis	591:625	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	4	14	dep	overexpression	536:549	arg1	cariogenicity					632:644	cariogenicity	632:644	cariogenicity	632:644	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	2	15	theme	bacterial	224:232	arg1	adaptation					234:243	bacterial adaptation	224:243	bacterial adaptation	224:243	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	1	16	theme	major	100:104	arg1	pathogen					117:124	a major cariogenic pathogen	98:124	a major cariogenic pathogen that resides in multispecies oral microbial biofilms	98:177	Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms.
31821772	1	16	theme	major	100:104	arg1	mutans					88:93	Streptococcus mutans	74:93	Streptococcus mutans	74:93	Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms.
31821772	13	17	theme	implications	1972:1983	arg1	number					1962:1967	a number	1960:1967	a number of implications	1960:1983	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	9	18	theme	vicR	1293:1296	arg1	gene					1298:1301	the vicR gene	1289:1301	the vicR gene	1289:1301	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	2	19	theme	biofilm	261:267	arg1	organization					269:280	biofilm organization	261:280	biofilm organization	261:280	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	11	20	theme	caries-free	1527:1537	arg1	children					1539:1546	caries-free children	1527:1546	caries-free children	1527:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	7	21	theme	molecular	1032:1040	arg1	weights					1042:1048	much lower molecular weights	1021:1048	much lower molecular weights	1021:1048	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	1	22	theme	oral	155:158	arg1	biofilms					170:177	multispecies oral microbial biofilms	142:177	multispecies oral microbial biofilms	142:177	Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms.
31821772	11	23	theme	ASvicR	1573:1578	arg1	expression					1559:1568	the expression	1555:1568	the expression of ASvicR	1555:1578	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	5	24	theme	carbohydrate	724:735	arg1	metabolism					737:746	carbohydrate metabolism	724:746	carbohydrate metabolism	724:746	Transcriptome analysis revealed that the ASvicR RNA mainly regulated carbohydrate metabolism.
31821772	9	25	theme	T4	1169:1170	arg1	ligase					1176:1181	T4 RNA ligase	1169:1181	T4 RNA ligase	1169:1181	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	0	26	from	RNA	52:54	arg1	Cariogenicity					59:71	Cariogenicity	59:71	Cariogenicity	59:71	Carbohydrate Metabolism Regulated by Antisense vicR RNA in Cariogenicity.
31821772	3	27	theme	RNase	422:426	arg1	relevant					461:468	relevant	461:468	relevant	461:468	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	27	theme	RNase	422:426	arg1	gene					447:450	an adjacent RNase III-encoding (rnc) gene	410:450	an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs)	410:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	13	28	theme	regulatory	2106:2115	arg1	RNAs					2117:2120	regulatory RNAs	2106:2120	regulatory RNAs	2106:2120	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	11	29	theme	transcript	1474:1483	arg1	levels					1485:1490	ASvicR transcript levels	1467:1490	ASvicR transcript levels in clinical S. mutans strains from caries-free children	1467:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	0	30	theme	Carbohydrate	0:11	arg1	Metabolism					13:22	Carbohydrate Metabolism	0:22	Carbohydrate Metabolism	0:22	Carbohydrate Metabolism Regulated by Antisense vicR RNA in Cariogenicity.
31821772	8	31	theme	rnc-encoded	1121:1131	arg1	RNase					1133:1137	rnc-encoded RNase III	1121:1141	rnc-encoded RNase III	1121:1141	Furthermore, direct evidence showed that total RNAs were disrupted by rnc-encoded RNase III.
31821772	7	32	theme	water-insoluble	966:980	arg1	glucans					982:988	the water-insoluble glucans	962:988	the water-insoluble glucans isolated from ASvicR	962:1009	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	9	33	theme	RNA	1172:1174	arg1	ligase					1176:1181	T4 RNA ligase	1169:1181	T4 RNA ligase	1169:1181	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	3	34	theme	antisense	366:374	arg1	RNA					381:383	an antisense vicR RNA	363:383	an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs)	363:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	34	theme	antisense	366:374	arg1	ASvicR					386:391	ASvicR	386:391	ASvicR	386:391	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	13	35	theme	gene	2034:2037	arg1	regulation					2039:2048	bacterial gene regulation	2024:2048	bacterial gene regulation	2024:2048	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	12	36	theme	response	1903:1910	arg1	regulator					1912:1920	a vital response regulator	1895:1920	a vital response regulator in cariogenicity	1895:1937	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	1	37	theme	cariogenic	106:115	arg1	pathogen					117:124	a major cariogenic pathogen	98:124	a major cariogenic pathogen that resides in multispecies oral microbial biofilms	98:177	Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms.
31821772	1	37	theme	cariogenic	106:115	arg1	mutans					88:93	Streptococcus mutans	74:93	Streptococcus mutans	74:93	Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms.
31821772	12	38	from	role	1782:1785	arg1	mutans					1830:1835	S. mutans	1827:1835	S. mutans	1827:1835	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	2	39	theme	VicRK	184:188	arg1	crucial					212:218	crucial	212:218	crucial	212:218	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	39	theme	VicRK	184:188	arg1	system					202:207	The VicRK 2-component system	180:207	The VicRK 2-component system	180:207	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	11	40	theme	S.	1504:1505	arg1	strains					1514:1520	clinical S. mutans strains	1495:1520	clinical S. mutans strains from caries-free children	1495:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	0	41	theme	Antisense	37:45	arg1	RNA					52:54	Antisense vicR RNA	37:54	Antisense vicR RNA in Cariogenicity	37:71	Carbohydrate Metabolism Regulated by Antisense vicR RNA in Cariogenicity.
31821772	12	42	theme	metabolism	1881:1890	arg1	characterization					1853:1868	the characterization	1849:1868	the characterization of lactose metabolism	1849:1890	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	6	43	theme	composition	864:874	arg1	analysis					876:883	monosaccharide composition analysis	849:883	monosaccharide composition analysis	849:883	In particular, overproducing ASvicR demonstrated a reduction in galactose and glucose metabolism by monosaccharide composition analysis.
31821772	12	44	theme	lactose	1873:1879	arg1	metabolism					1881:1890	lactose metabolism	1873:1890	lactose metabolism	1873:1890	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	12	45	theme	important	1772:1780	arg1	role					1782:1785	an important role	1769:1785	an important role of ASvicR-mediated sponge regulation in S. mutans	1769:1835	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	10	46	theme	regulatory-mediated	1353:1371	arg1	network					1373:1379	a sponge regulatory-mediated network	1344:1379	a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes	1344:1439	Furthermore, ASvicR regulation revealed a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes.
31821772	6	47	theme	overproducing	764:776	arg1	ASvicR					778:783	overproducing ASvicR	764:783	overproducing ASvicR	764:783	In particular, overproducing ASvicR demonstrated a reduction in galactose and glucose metabolism by monosaccharide composition analysis.
31821772	4	48	theme	bacterial	573:581	arg1	growth					583:588	significantly impeded bacterial growth	551:588	significantly impeded bacterial growth	551:588	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	10	49	theme	adjacent	1407:1414	arg1	genes					1435:1439	adjacent RNase III-encoding genes	1407:1439	adjacent RNase III-encoding genes	1407:1439	Furthermore, ASvicR regulation revealed a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes.
31821772	13	50	theme	transcriptional	2059:2073	arg1	conception					2075:2084	its transcriptional conception	2055:2084	its transcriptional conception to the key roles of regulatory RNAs	2055:2120	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	3	51	theme	microRNA-size	473:485	arg1	msRNAs					499:504	msRNAs	499:504	msRNAs	499:504	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	51	theme	microRNA-size	473:485	arg1	RNAs					493:496	microRNA-size small RNAs	473:496	microRNA-size small RNAs (msRNAs)	473:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	7	52	theme	permeation	922:931	arg1	chromatography					933:946	high-performance gel permeation chromatography	901:946	high-performance gel permeation chromatography	901:946	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	12	53	theme	sponge	1806:1811	arg1	regulation					1813:1822	ASvicR-mediated sponge regulation	1790:1822	ASvicR-mediated sponge regulation	1790:1822	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	4	54	theme	ASvicR	529:534	arg1	overexpression					536:549	that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo	524:652	that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo	524:652	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	9	55	theme	messenger	1228:1236	arg1	RNA					1238:1240	an rnc-related messenger RNA	1213:1240	an rnc-related messenger RNA	1213:1240	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	9	55	theme	messenger	1228:1236	arg1	msRNA1657					1193:1201	putative msRNA1657	1184:1201	putative msRNA1657	1184:1201	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	2	56	theme	global	297:302	arg1	VicR					334:337	VicR	334:337	VicR	334:337	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	56	theme	global	297:302	arg1	regulator					323:331	a global and vital response regulator	295:331	a global and vital response regulator	295:331	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	7	57	theme	high-performance	901:916	arg1	chromatography					933:946	high-performance gel permeation chromatography	901:946	high-performance gel permeation chromatography	901:946	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	11	58	theme	dental	1717:1722	arg1	caries					1724:1729	dental caries	1717:1729	dental caries	1717:1729	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	10	59	theme	III-encoding	1422:1433	arg1	genes					1435:1439	adjacent RNase III-encoding genes	1407:1439	adjacent RNase III-encoding genes	1407:1439	Furthermore, ASvicR regulation revealed a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes.
31821772	8	60	theme	direct	1064:1069	arg1	evidence					1071:1078	direct evidence	1064:1078	direct evidence	1064:1078	Furthermore, direct evidence showed that total RNAs were disrupted by rnc-encoded RNase III.
31821772	11	61	theme	childhood	1603:1611	arg1	patients					1620:1627	early childhood caries patients	1597:1627	early childhood caries patients	1597:1627	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	2	62	theme	vital	308:312	arg1	VicR					334:337	VicR	334:337	VicR	334:337	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	62	theme	vital	308:312	arg1	regulator					323:331	a global and vital response regulator	295:331	a global and vital response regulator	295:331	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	12	63	from	regulator	1912:1920	arg1	cariogenicity					1925:1937	cariogenicity	1925:1937	cariogenicity	1925:1937	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	4	64	theme	exopolysaccharide	599:615	arg1	synthesis					617:625	biofilm exopolysaccharide synthesis	591:625	biofilm exopolysaccharide synthesis	591:625	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	5	65	theme	Transcriptome	655:667	arg1	analysis					669:676	Transcriptome analysis	655:676	Transcriptome analysis	655:676	Transcriptome analysis revealed that the ASvicR RNA mainly regulated carbohydrate metabolism.
31821772	13	66	theme	key	2093:2095	arg1	roles					2097:2101	the key roles	2089:2101	the key roles of regulatory RNAs	2089:2120	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	9	67	theme	gene	1298:1301	arg1	regions					1278:1284	the 5'-UTR regions	1267:1284	the 5'-UTR regions of the vicR gene	1267:1301	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	1	68	theme	multispecies	142:153	arg1	biofilms					170:177	multispecies oral microbial biofilms	142:177	multispecies oral microbial biofilms	142:177	Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms.
31821772	8	69	theme	total	1092:1096	arg1	RNAs					1098:1101	total RNAs	1092:1101	total RNAs	1092:1101	Furthermore, direct evidence showed that total RNAs were disrupted by rnc-encoded RNase III.
31821772	1	70	theme	microbial	160:168	arg1	biofilms					170:177	multispecies oral microbial biofilms	142:177	multispecies oral microbial biofilms	142:177	Streptococcus mutans is a major cariogenic pathogen that resides in multispecies oral microbial biofilms.
31821772	7	71	theme	lower	1026:1030	arg1	weights					1042:1048	much lower molecular weights	1021:1048	much lower molecular weights	1021:1048	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	13	72	theme	regulation	2039:2048	arg1	understanding					2007:2019	our understanding	2003:2019	our understanding of bacterial gene regulation	2003:2048	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	13	73	contain	have	1955:1958	arg1	findings					1946:1953	These findings	1940:1953	These findings	1940:1953	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	13	73	contain	have	1955:1958	arg2	number					1962:1967	a number	1960:1967	a number of implications	1960:1983	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	10	74	theme	ASvicR	1317:1322	arg1	regulation					1324:1333	ASvicR regulation	1317:1333	ASvicR regulation	1317:1333	Furthermore, ASvicR regulation revealed a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes.
31821772	11	75	theme	ASvicR	1467:1472	arg1	levels					1485:1490	ASvicR transcript levels	1467:1490	ASvicR transcript levels in clinical S. mutans strains from caries-free children	1467:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	3	76	theme	III-encoding	428:439	arg1	relevant					461:468	relevant	461:468	relevant	461:468	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	76	theme	III-encoding	428:439	arg1	gene					447:450	an adjacent RNase III-encoding (rnc) gene	410:450	an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs)	410:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	13	77	theme	RNAs	2117:2120	arg1	roles					2097:2101	the key roles	2089:2101	the key roles of regulatory RNAs	2089:2120	These findings have a number of implications and have reshaped our understanding of bacterial gene regulation from its transcriptional conception to the key roles of regulatory RNAs.
31821772	7	78	attach	isolated	990:997	arg1	ASvicR					1004:1009	ASvicR	1004:1009	ASvicR	1004:1009	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	7	78	attach	isolated	990:997	arg2	glucans					982:988	the water-insoluble glucans	962:988	the water-insoluble glucans isolated from ASvicR	962:1009	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	10	79	theme	sponge	1346:1351	arg1	network					1373:1379	a sponge regulatory-mediated network	1344:1379	a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes	1344:1439	Furthermore, ASvicR regulation revealed a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes.
31821772	3	80	theme	adjacent	413:420	arg1	relevant					461:468	relevant	461:468	relevant	461:468	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	80	theme	adjacent	413:420	arg1	gene					447:450	an adjacent RNase III-encoding (rnc) gene	410:450	an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs)	410:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	2	81	contain	contains	286:293	arg2	regulator					323:331	a global and vital response regulator	295:331	a global and vital response regulator	295:331	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	81	contain	contains	286:293	arg1	crucial					212:218	crucial	212:218	crucial	212:218	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	81	contain	contains	286:293	arg2	VicR					334:337	VicR	334:337	VicR	334:337	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	81	contain	contains	286:293	arg1	system					202:207	The VicRK 2-component system	180:207	The VicRK 2-component system	180:207	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	11	82	from	children	1539:1546	arg1	levels					1485:1490	ASvicR transcript levels	1467:1490	ASvicR transcript levels in clinical S. mutans strains from caries-free children	1467:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	11	82	from	children	1539:1546	arg1	strains					1514:1520	clinical S. mutans strains	1495:1520	clinical S. mutans strains from caries-free children	1495:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	3	83	theme	vicR	376:379	arg1	RNA					381:383	an antisense vicR RNA	363:383	an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs)	363:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	83	theme	vicR	376:379	arg1	ASvicR					386:391	ASvicR	386:391	ASvicR	386:391	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	2	84	theme	2-component	190:200	arg1	crucial					212:218	crucial	212:218	crucial	212:218	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	2	84	theme	2-component	190:200	arg1	system					202:207	The VicRK 2-component system	180:207	The VicRK 2-component system	180:207	The VicRK 2-component system is crucial for bacterial adaptation, virulence, and biofilm organization and contains a global and vital response regulator, VicR.
31821772	11	85	theme	clinical	1495:1502	arg1	strains					1514:1520	clinical S. mutans strains	1495:1520	clinical S. mutans strains from caries-free children	1495:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	0	86	theme	vicR	47:50	arg1	RNA					52:54	Antisense vicR RNA	37:54	Antisense vicR RNA in Cariogenicity	37:71	Carbohydrate Metabolism Regulated by Antisense vicR RNA in Cariogenicity.
31821772	6	87	from	reduction	800:808	arg1	metabolism					835:844	galactose and glucose metabolism	813:844	metabolism	835:844	In particular, overproducing ASvicR demonstrated a reduction in galactose and glucose metabolism by monosaccharide composition analysis.
31821772	11	88	theme	caries	1724:1729	arg1	management					1703:1712	the management	1699:1712	the management of dental caries	1699:1729	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	9	89	theme	ligase	1176:1181	arg1	coexpression					1153:1164	the coexpression	1149:1164	the coexpression of T4 RNA ligase	1149:1181	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	3	90	theme	rnc	442:444	arg1	relevant					461:468	relevant	461:468	relevant	461:468	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	3	90	theme	rnc	442:444	arg1	gene					447:450	an adjacent RNase III-encoding (rnc) gene	410:450	an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs)	410:505	Notably, we identified an antisense vicR RNA (ASvicR) associated with an adjacent RNase III-encoding (rnc) gene that was relevant to microRNA-size small RNAs (msRNAs).
31821772	9	91	theme	putative	1184:1191	arg1	RNA					1238:1240	an rnc-related messenger RNA	1213:1240	an rnc-related messenger RNA	1213:1240	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	9	91	theme	putative	1184:1191	arg1	msRNA1657					1193:1201	putative msRNA1657	1184:1201	putative msRNA1657	1184:1201	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	9	92	theme	5'-UTR	1271:1276	arg1	regions					1278:1284	the 5'-UTR regions	1267:1284	the 5'-UTR regions of the vicR gene	1267:1301	With the coexpression of T4 RNA ligase, putative msRNA1657, which is an rnc-related messenger RNA, was verified to bind to the 5'-UTR regions of the vicR gene.
31821772	12	93	theme	vital	1897:1901	arg1	regulator					1912:1920	a vital response regulator	1895:1920	a vital response regulator in cariogenicity	1895:1937	Taken together, our findings suggest an important role of ASvicR-mediated sponge regulation in S. mutans, indicating the characterization of lactose metabolism by a vital response regulator in cariogenicity.
31821772	6	94	theme	monosaccharide	849:862	arg1	analysis					876:883	monosaccharide composition analysis	849:883	monosaccharide composition analysis	849:883	In particular, overproducing ASvicR demonstrated a reduction in galactose and glucose metabolism by monosaccharide composition analysis.
31821772	11	95	from	increase	1455:1462	arg1	levels					1485:1490	ASvicR transcript levels	1467:1490	ASvicR transcript levels in clinical S. mutans strains from caries-free children	1467:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	10	96	theme	RNase	1416:1420	arg1	genes					1435:1439	adjacent RNase III-encoding genes	1407:1439	adjacent RNase III-encoding genes	1407:1439	Furthermore, ASvicR regulation revealed a sponge regulatory-mediated network for msRNA associated with adjacent RNase III-encoding genes.
31821772	7	97	theme	chromatography	933:946	arg1	results					890:896	The results	886:896	The results of high-performance gel permeation chromatography	886:946	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
31821772	11	98	from	levels	1485:1490	arg1	children					1539:1546	caries-free children	1527:1546	caries-free children	1527:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	11	98	from	levels	1485:1490	arg1	strains					1514:1520	clinical S. mutans strains	1495:1520	clinical S. mutans strains from caries-free children	1495:1546	There was an increase in ASvicR transcript levels in clinical S. mutans strains from caries-free children, while the expression of ASvicR was decreased in early childhood caries patients; this outcome may be explored as a potential strategy contributing to the management of dental caries.
31821772	4	99	theme	biofilm	591:597	arg1	synthesis					617:625	biofilm exopolysaccharide synthesis	591:625	biofilm exopolysaccharide synthesis	591:625	Here, we report that ASvicR overexpression significantly impeded bacterial growth, biofilm exopolysaccharide synthesis, and cariogenicity in vivo.
31821772	7	100	theme	gel	918:920	arg1	chromatography					933:946	high-performance gel permeation chromatography	901:946	high-performance gel permeation chromatography	901:946	The results of high-performance gel permeation chromatography revealed that the water-insoluble glucans isolated from ASvicR presented much lower molecular weights.
30838579	4	0	from	extraction	511:520	arg1	matrices					555:562	the bone and dentin matrices	535:562	matrices	555:562	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	0	from	extraction	511:520	arg1	NCPs					636:639	NCPs	636:639	NCPs	636:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	1	1	contain	contains	109:116	arg2	NCPs					152:155	NCPs	152:155	NCPs	152:155	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	1	1	contain	contains	109:116	arg2	proteins					142:149	several non-collagenous proteins	118:149	several non-collagenous proteins (NCPs)	118:156	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	1	1	contain	contains	109:116	arg1	matrix					79:84	The extracellular matrix	61:84	The extracellular matrix of the bone and dentin	61:107	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	3	2	theme	abundant	416:423	arg1	phosphoserines					425:438	abundant phosphoserines	416:438	abundant phosphoserines	416:438	These proteins have abundant phosphoserines, aspartic acids, and glutamic acids.
30838579	4	3	from	isolation	597:605	arg1	matrices					555:562	the bone and dentin matrices	535:562	matrices	555:562	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	3	from	isolation	597:605	arg1	NCPs					636:639	NCPs	636:639	NCPs	636:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	4	theme	gradient	785:792	arg1	elution					794:800	a gradient elution	783:800	a gradient elution by NaCl	783:808	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	5	theme	SIBLING	194:200	arg1	family					257:262	the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family	190:262	the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family	190:262	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	5	theme	SIBLING	194:200	arg1	ligand					226:231	small integrin-binding ligand	203:231	small integrin-binding ligand	203:231	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	4	6	theme	fast	660:663	arg1	chromatography					680:693	ion-exchange fast protein liquid chromatography	647:693	ion-exchange fast protein liquid chromatography (FPLC)	647:700	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	6	theme	fast	660:663	arg1	FPLC					696:699	FPLC	696:699	FPLC	696:699	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	7	link	N-linked	234:241	arg1	glycoprotein					243:254	N-linked glycoprotein	234:254	N-linked glycoprotein	234:254	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	0	8	from	Dentin	44:49	arg1	Isolation					0:8	Isolation	0:8	Isolation of SIBLING Proteins from Bone and Dentin Matrices.	0:59	Isolation of SIBLING Proteins from Bone and Dentin Matrices.
30838579	4	9	theme	liquid	673:678	arg1	chromatography					680:693	ion-exchange fast protein liquid chromatography	647:693	ion-exchange fast protein liquid chromatography (FPLC)	647:700	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	9	theme	liquid	673:678	arg1	FPLC					696:699	FPLC	696:699	FPLC	696:699	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	3	10	theme	glutamic	461:468	arg1	acids					470:474	glutamic acids	461:474	glutamic acids	461:474	These proteins have abundant phosphoserines, aspartic acids, and glutamic acids.
30838579	2	11	gly	glycoprotein	243:254	arg1	glycoprotein					243:254	N-linked glycoprotein	234:254	N-linked glycoprotein	234:254	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	4	12	theme	SIBLINGs	622:629	arg1	isolation					597:605	the isolation	593:605	the isolation of polyanionic SIBLINGs from NCPs	593:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	12	theme	SIBLINGs	622:629	arg1	extraction					511:520	the extraction	507:520	the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA	507:587	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	13	dep	ligand	226:231	arg1	glycoprotein					243:254	N-linked glycoprotein	234:254	N-linked glycoprotein	234:254	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	0	14	from	Bone	35:38	arg1	Isolation					0:8	Isolation	0:8	Isolation of SIBLING Proteins from Bone and Dentin Matrices.	0:59	Isolation of SIBLING Proteins from Bone and Dentin Matrices.
30838579	4	15	theme	different	755:763	arg1	fractions					765:773	different fractions	755:773	different fractions	755:773	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	1	16	theme	extracellular	65:77	arg1	matrix					79:84	The extracellular matrix	61:84	The extracellular matrix of the bone and dentin	61:107	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	4	17	from	matrices	555:562	arg1	isolation					597:605	the isolation	593:605	the isolation of polyanionic SIBLINGs from NCPs	593:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	17	from	matrices	555:562	arg1	extraction					511:520	the extraction	507:520	the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA	507:587	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	17	from	matrices	555:562	arg1	NCPs					525:528	NCPs	525:528	NCPs from the bone and dentin matrices using guanidine-HCl/EDTA	525:587	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	18	theme	matrix	331:336	arg1	osteopontin					280:290	osteopontin	280:290	osteopontin (OPN)	280:296	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	18	theme	matrix	331:336	arg1	protein					338:344	dentin matrix protein 1	324:346	dentin matrix protein 1 (DMP1)	324:353	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	18	theme	matrix	331:336	arg1	DMP1					349:352	DMP1	349:352	DMP1	349:352	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	4	19	theme	ion-exchange	647:658	arg1	chromatography					680:693	ion-exchange fast protein liquid chromatography	647:693	ion-exchange fast protein liquid chromatography (FPLC)	647:700	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	19	theme	ion-exchange	647:658	arg1	FPLC					696:699	FPLC	696:699	FPLC	696:699	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	20	theme	dentin	324:329	arg1	osteopontin					280:290	osteopontin	280:290	osteopontin (OPN)	280:296	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	20	theme	dentin	324:329	arg1	protein					338:344	dentin matrix protein 1	324:346	dentin matrix protein 1 (DMP1)	324:353	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	20	theme	dentin	324:329	arg1	DMP1					349:352	DMP1	349:352	DMP1	349:352	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	21	theme	dentin	356:361	arg1	sialophosphoprotein					363:381	dentin sialophosphoprotein	356:381	dentin sialophosphoprotein (DSPP)	356:388	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	21	theme	dentin	356:361	arg1	osteopontin					280:290	osteopontin	280:290	osteopontin (OPN)	280:296	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	21	theme	dentin	356:361	arg1	DSPP					384:387	DSPP	384:387	DSPP	384:387	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	4	22	theme	protein	665:671	arg1	chromatography					680:693	ion-exchange fast protein liquid chromatography	647:693	ion-exchange fast protein liquid chromatography (FPLC)	647:700	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	22	theme	protein	665:671	arg1	FPLC					696:699	FPLC	696:699	FPLC	696:699	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	23	theme	charged	733:739	arg1	proteins					741:748	the differentially charged proteins	714:748	the differentially charged proteins	714:748	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	0	24	theme	SIBLING	13:19	arg1	Proteins					21:28	SIBLING Proteins	13:28	SIBLING Proteins	13:28	Isolation of SIBLING Proteins from Bone and Dentin Matrices.
30838579	1	25	theme	bone	93:96	arg1	matrix					79:84	The extracellular matrix	61:84	The extracellular matrix of the bone and dentin	61:107	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	4	26	theme	polyanionic	610:620	arg1	SIBLINGs					622:629	polyanionic SIBLINGs	610:629	polyanionic SIBLINGs from NCPs	610:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	27	theme	small	203:207	arg1	family					257:262	the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family	190:262	the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family	190:262	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	27	theme	small	203:207	arg1	ligand					226:231	small integrin-binding ligand	203:231	small integrin-binding ligand	203:231	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	0	28	theme	Proteins	21:28	arg1	Isolation					0:8	Isolation	0:8	Isolation of SIBLING Proteins from Bone and Dentin Matrices.	0:59	Isolation of SIBLING Proteins from Bone and Dentin Matrices.
30838579	4	29	theme	bone	539:542	arg1	matrices					555:562	the bone and dentin matrices	535:562	matrices	555:562	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	0	30	dep	Bone	35:38	arg1	Matrices					51:58	Matrices	51:58	Matrices	51:58	Isolation of SIBLING Proteins from Bone and Dentin Matrices.
30838579	3	31	contain	have	411:414	arg1	proteins					402:409	These proteins	396:409	These proteins	396:409	These proteins have abundant phosphoserines, aspartic acids, and glutamic acids.
30838579	3	31	contain	have	411:414	arg2	acids					450:454	aspartic acids	441:454	aspartic acids	441:454	These proteins have abundant phosphoserines, aspartic acids, and glutamic acids.
30838579	3	31	contain	have	411:414	arg2	phosphoserines					425:438	abundant phosphoserines	416:438	abundant phosphoserines	416:438	These proteins have abundant phosphoserines, aspartic acids, and glutamic acids.
30838579	3	31	contain	have	411:414	arg2	acids					470:474	glutamic acids	461:474	glutamic acids	461:474	These proteins have abundant phosphoserines, aspartic acids, and glutamic acids.
30838579	2	32	theme	bone	299:302	arg1	osteopontin					280:290	osteopontin	280:290	osteopontin (OPN)	280:296	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	32	theme	bone	299:302	arg1	BSP					318:320	BSP	318:320	BSP	318:320	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	32	theme	bone	299:302	arg1	sialoprotein					304:315	bone sialoprotein	299:315	bone sialoprotein (BSP)	299:321	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	1	33	theme	dentin	102:107	arg1	matrix					79:84	The extracellular matrix	61:84	The extracellular matrix of the bone and dentin	61:107	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	4	34	from	NCPs	636:639	arg1	isolation					597:605	the isolation	593:605	the isolation of polyanionic SIBLINGs from NCPs	593:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	34	from	NCPs	636:639	arg1	extraction					511:520	the extraction	507:520	the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA	507:587	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	34	from	NCPs	636:639	arg1	SIBLINGs					622:629	polyanionic SIBLINGs	610:629	polyanionic SIBLINGs from NCPs	610:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	35	theme	N-linked	234:241	arg1	glycoprotein					243:254	N-linked glycoprotein	234:254	N-linked glycoprotein	234:254	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	36	theme	NCPs	175:178	arg1	category					163:170	One category	159:170	One category of NCPs	159:178	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	1	37	theme	several	118:124	arg1	proteins					142:149	several non-collagenous proteins	118:149	several non-collagenous proteins (NCPs)	118:156	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	1	37	theme	several	118:124	arg1	NCPs					152:155	NCPs	152:155	NCPs	152:155	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	1	38	theme	non-collagenous	126:140	arg1	proteins					142:149	several non-collagenous proteins	118:149	several non-collagenous proteins (NCPs)	118:156	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	1	38	theme	non-collagenous	126:140	arg1	NCPs					152:155	NCPs	152:155	NCPs	152:155	The extracellular matrix of the bone and dentin contains several non-collagenous proteins (NCPs).
30838579	4	39	theme	dentin	548:553	arg1	matrices					555:562	the bone and dentin matrices	535:562	matrices	555:562	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	40	theme	NCPs	525:528	arg1	isolation					597:605	the isolation	593:605	the isolation of polyanionic SIBLINGs from NCPs	593:639	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	4	40	theme	NCPs	525:528	arg1	extraction					511:520	the extraction	507:520	the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA	507:587	In this protocol, we describe the extraction of NCPs from the bone and dentin matrices using guanidine-HCl/EDTA and the isolation of polyanionic SIBLINGs from NCPs using ion-exchange fast protein liquid chromatography (FPLC) to separate the differentially charged proteins into different fractions through a gradient elution by NaCl.
30838579	2	41	theme	integrin-binding	209:224	arg1	family					257:262	the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family	190:262	the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family	190:262	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	2	41	theme	integrin-binding	209:224	arg1	ligand					226:231	small integrin-binding ligand	203:231	small integrin-binding ligand	203:231	One category of NCPs is termed the SIBLING (small integrin-binding ligand, N-linked glycoprotein) family, which includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), etc.
30838579	3	42	theme	aspartic	441:448	arg1	acids					450:454	aspartic acids	441:454	aspartic acids	441:454	These proteins have abundant phosphoserines, aspartic acids, and glutamic acids.
31892091	4	0	theme	optimized	794:802	arg1	conditions					804:813	the optimized conditions	790:813	the optimized conditions	790:813	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	1	1	theme	solid-phase	175:185	arg1	method					259:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method	147:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	5	2	contain	containing	1068:1077	arg2	NeuGc					1089:1093	NeuGc	1089:1093	NeuGc	1089:1093	The method was linear between 0.5 and 50 mg L-1 and 10-50 mg L-1 for O126 glycoforms containing NeuAc and NeuGc, respectively, and limits of detection (LODs) were up to 100 times lower than by CE-MS.
31892091	5	2	contain	containing	1068:1077	arg2	NeuAc					1079:1083	NeuAc	1079:1083	NeuAc	1079:1083	The method was linear between 0.5 and 50 mg L-1 and 10-50 mg L-1 for O126 glycoforms containing NeuAc and NeuGc, respectively, and limits of detection (LODs) were up to 100 times lower than by CE-MS.
31892091	5	2	contain	containing	1068:1077	arg1	glycoforms					1057:1066	O126 glycoforms	1052:1066	O126 glycoforms containing NeuAc and NeuGc, respectively	1052:1107	The method was linear between 0.5 and 50 mg L-1 and 10-50 mg L-1 for O126 glycoforms containing NeuAc and NeuGc, respectively, and limits of detection (LODs) were up to 100 times lower than by CE-MS.
31892091	1	3	theme	glycopeptide	290:301	arg1	glycoforms					303:312	the glycopeptide glycoforms	286:312	the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	286:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	0	4	theme	electrophoresis-mass	85:104	arg1	spectrometry					106:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	4	5	theme	migration	936:944	arg1	times					946:950	migration times	936:950	migration times	936:950	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	1	6	theme	extraction	187:196	arg1	method					259:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method	147:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	1	7	theme	glycoforms	303:312	arg1	analysis					274:281	the analysis	270:281	the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	270:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	7	8	gly	glycoprotein	1511:1522	arg1	bAGP					1525:1528	bAGP	1525:1528	bAGP	1525:1528	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	7	8	gly	glycoprotein	1511:1522	arg1	glycoprotein					1511:1522	bovine alpha-1-acid glycoprotein	1491:1522	bovine alpha-1-acid glycoprotein (bAGP)	1491:1529	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	4	9	theme	peak	956:959	arg1	areas					961:965	peak areas	956:965	peak areas	956:965	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	4	10	theme	%	920:920	arg1	values					906:911	%RSD values	901:911	%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively	901:979	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	7	11	theme	alpha-1-acid	1498:1509	arg1	bAGP					1525:1528	bAGP	1525:1528	bAGP	1525:1528	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	7	11	theme	alpha-1-acid	1498:1509	arg1	glycoprotein					1511:1522	bovine alpha-1-acid glycoprotein	1491:1522	bovine alpha-1-acid glycoprotein (bAGP)	1491:1529	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	7	12	gly	glycopeptides	1587:1599	arg2	glycopeptides					1587:1599	glycopeptides	1587:1599	glycopeptides with different glycan composition and nature	1587:1644	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	6	13	gly	N83-glycopeptides	1281:1297	arg2	N83-glycopeptides					1281:1297	N83-glycopeptides	1281:1297	N83-glycopeptides	1281:1297	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	3	14	theme	peak	609:612	arg1	efficiency					614:623	peak efficiency	609:623	peak efficiency	609:623	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	3	15	theme	Several	544:550	arg1	aspects					552:558	Several aspects	544:558	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms	544:677	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	7	16	theme	apolipoprotein	1458:1471	arg1	APO-C3					1479:1484	APO-C3	1479:1484	APO-C3	1479:1484	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	7	16	theme	apolipoprotein	1458:1471	arg1	CIII					1473:1476	human apolipoprotein CIII	1452:1476	human apolipoprotein CIII (APO-C3)	1452:1485	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	1	17	theme	capillary	198:206	arg1	method					259:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method	147:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	2	18	theme	biopharmaceuticals	504:521	arg1	control					493:499	quality control	485:499	quality control of biopharmaceuticals and doping analysis	485:541	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	2	19	theme	analysis	534:541	arg1	control					493:499	quality control	485:499	quality control of biopharmaceuticals and doping analysis	485:541	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	7	20	theme	bovine	1491:1496	arg1	bAGP					1525:1528	bAGP	1525:1528	bAGP	1525:1528	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	7	20	theme	bovine	1491:1496	arg1	glycoprotein					1511:1522	bovine alpha-1-acid glycoprotein	1491:1522	bovine alpha-1-acid glycoprotein (bAGP)	1491:1529	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	1	21	theme	electrophoresis-mass	208:227	arg1	method					259:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method	147:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	7	22	gly	glycoproteins	1432:1444	arg1	glycoproteins					1432:1444	other glycoproteins	1426:1444	other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP))	1426:1530	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	5	23	theme	100	1152:1154	arg1	times					1156:1160	times	1156:1160	times	1156:1160	The method was linear between 0.5 and 50 mg L-1 and 10-50 mg L-1 for O126 glycoforms containing NeuAc and NeuGc, respectively, and limits of detection (LODs) were up to 100 times lower than by CE-MS.
31892091	1	24	gly	glycopeptide	290:301	arg2	glycopeptide					290:301	glycopeptide	290:301	glycopeptide	290:301	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	3	25	theme	electrophoretic	629:643	arg1	separation					645:654	electrophoretic separation	629:654	electrophoretic separation	629:654	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	1	26	theme	spectrometry	229:240	arg1	method					259:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method	147:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	6	27	theme	acids	1400:1404	arg1	number					1383:1388	different number	1373:1388	different number of sialic acids	1373:1404	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	4	28	theme	%	930:930	arg1	values					906:911	%RSD values	901:911	%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively	901:979	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	6	29	gly	O-glycopeptides	1206:1220	arg2	O-glycopeptides					1206:1220	O-glycopeptides	1206:1220	O-glycopeptides	1206:1220	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	4	30	dep	acceptable	889:898	arg1	values					906:911	%RSD values	901:911	%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively	901:979	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	0	31	theme	biomarkers	25:34	arg1	Analysis					0:7	Analysis	0:7	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.	0:118	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	1	32	theme	tryptic	332:338	arg1	digests					340:346	the tryptic digests	328:346	the tryptic digests of recombinant human erythropoietin (rhEPO)	328:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	7	33	theme	human	1452:1456	arg1	APO-C3					1479:1484	APO-C3	1479:1484	APO-C3	1479:1484	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	7	33	theme	human	1452:1456	arg1	CIII					1473:1476	human apolipoprotein CIII	1452:1476	human apolipoprotein CIII (APO-C3)	1452:1485	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	1	34	theme	TiO2-SPE-CE-MS	243:256	arg1	method					259:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method	147:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	0	35	theme	glycopeptide	12:23	arg1	biomarkers					25:34	glycopeptide biomarkers	12:34	glycopeptide biomarkers	12:34	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	5	36	dep	times	1156:1160	arg1	to					1149:1150	to	1149:1150	to	1149:1150	The method was linear between 0.5 and 50 mg L-1 and 10-50 mg L-1 for O126 glycoforms containing NeuAc and NeuGc, respectively, and limits of detection (LODs) were up to 100 times lower than by CE-MS.
31892091	5	36	dep	times	1156:1160	arg1	lower					1162:1166	lower	1162:1166	lower	1162:1166	The method was linear between 0.5 and 50 mg L-1 and 10-50 mg L-1 for O126 glycoforms containing NeuAc and NeuGc, respectively, and limits of detection (LODs) were up to 100 times lower than by CE-MS.
31892091	5	37	theme	detection	1124:1132	arg1	limits					1114:1119	limits	1114:1119	limits of detection (LODs)	1114:1139	The method was linear between 0.5 and 50 mg L-1 and 10-50 mg L-1 for O126 glycoforms containing NeuAc and NeuGc, respectively, and limits of detection (LODs) were up to 100 times lower than by CE-MS.
31892091	3	38	theme	selective	576:584	arg1	retention					586:594	the selective retention	572:594	the selective retention	572:594	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	0	39	theme	on-line	39:45	arg1	spectrometry					106:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	2	40	gly	O126-glycopeptide	397:413	arg1	rhEPO					418:422	rhEPO	418:422	rhEPO	418:422	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	2	40	gly	O126-glycopeptide	397:413	arg2	O126-glycopeptide					397:413	The O126-glycopeptide	393:413	The O126-glycopeptide of rhEPO	393:422	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	7	41	theme	glycan	1616:1621	arg1	composition					1623:1633	different glycan composition	1606:1633	different glycan composition	1606:1633	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	6	42	theme	N83-glycopeptides	1281:1297	arg1	preconcentration					1261:1276	preconcentration	1261:1276	preconcentration of N83-glycopeptides	1261:1297	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	7	43	with	glycopeptides	1587:1599	arg1	nature					1639:1644	nature	1639:1644	nature	1639:1644	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	7	43	with	glycopeptides	1587:1599	arg1	composition					1623:1633	different glycan composition	1606:1633	different glycan composition	1606:1633	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	2	44	theme	doping	527:532	arg1	analysis					534:541	doping analysis	527:541	doping analysis	527:541	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	1	45	theme	recombinant	351:361	arg1	rhEPO					385:389	rhEPO	385:389	rhEPO	385:389	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	1	45	theme	recombinant	351:361	arg1	erythropoietin					369:382	recombinant human erythropoietin	351:382	recombinant human erythropoietin (rhEPO)	351:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	6	46	theme	sialic	1393:1398	arg1	acids					1400:1404	sialic acids	1393:1404	sialic acids	1393:1404	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	3	47	theme	detection	709:717	arg1	sensitivity					719:729	detection sensitivity	709:729	detection sensitivity	709:729	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	2	48	theme	quality	485:491	arg1	control					493:499	quality control	485:499	quality control of biopharmaceuticals and doping analysis	485:541	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	0	49	theme	solid-phase	52:62	arg1	spectrometry					106:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	1	50	theme	human	363:367	arg1	rhEPO					385:389	rhEPO	385:389	rhEPO	385:389	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	1	50	theme	human	363:367	arg1	erythropoietin					369:382	recombinant human erythropoietin	351:382	recombinant human erythropoietin (rhEPO)	351:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	0	51	gly	glycopeptide	12:23	arg2	glycopeptide					12:23	glycopeptide biomarkers	12:34	glycopeptide biomarkers	12:34	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	6	52	theme	different	1373:1381	arg1	number					1383:1388	different number	1373:1388	different number of sialic acids	1373:1404	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	0	53	theme	TiO2	47:50	arg1	spectrometry					106:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	1	54	theme	erythropoietin	369:382	arg1	digests					340:346	the tryptic digests	328:346	the tryptic digests of recombinant human erythropoietin (rhEPO)	328:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	6	55	gly	glycopeptide	1344:1355	arg2	glycopeptide					1344:1355	glycopeptide	1344:1355	glycopeptide	1344:1355	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	2	56	theme	rhEPO	418:422	arg1	O126-glycopeptide					397:413	The O126-glycopeptide	393:413	The O126-glycopeptide of rhEPO	393:422	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	6	57	theme	glycopeptide	1344:1355	arg1	glycoforms					1357:1366	glycopeptide glycoforms	1344:1366	glycopeptide glycoforms with different number of sialic acids	1344:1404	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	3	58	theme	peptides	774:781	arg1	retention					761:769	non-specific retention	748:769	non-specific retention of peptides	748:781	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	7	59	theme	other	1426:1430	arg1	glycoproteins					1432:1444	other glycoproteins	1426:1444	other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP))	1426:1530	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	3	60	theme	glycoforms	668:677	arg1	separation					645:654	electrophoretic separation	629:654	electrophoretic separation	629:654	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	3	60	theme	glycoforms	668:677	arg1	elution					600:606	elution	600:606	elution	600:606	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	3	60	theme	glycoforms	668:677	arg1	efficiency					614:623	peak efficiency	609:623	peak efficiency	609:623	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	3	60	theme	glycoforms	668:677	arg1	retention					586:594	the selective retention	572:594	the selective retention	572:594	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	4	61	theme	microcartridge	820:833	arg1	lifetime					835:842	the microcartridge lifetime	816:842	the microcartridge lifetime	816:842	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	3	62	theme	non-specific	748:759	arg1	retention					761:769	non-specific retention	748:769	non-specific retention of peptides	748:781	Several aspects that affect the selective retention and elution, peak efficiency and electrophoretic separation of the O126 glycoforms were investigated to maximize detection sensitivity while minimizing non-specific retention of peptides.
31892091	7	63	theme	glycoproteins	1432:1444	arg1	digests					1415:1421	Tryptic digests	1407:1421	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP))	1407:1530	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	2	64	used	used	428:431	arg2	O126-glycopeptide					397:413	The O126-glycopeptide	393:413	The O126-glycopeptide of rhEPO	393:422	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	1	65	theme	on-line	150:156	arg1	dioxide					167:173	an on-line titanium dioxide	147:173	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	6	66	with	glycoforms	1357:1366	arg1	number					1383:1388	different number	1373:1388	different number of sialic acids	1373:1404	Although optimized for O-glycopeptides, the method proved also successful for preconcentration of N83-glycopeptides, without compromising the separation between glycopeptide glycoforms with different number of sialic acids.
31892091	0	67	theme	capillary	75:83	arg1	spectrometry					106:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	4	68	theme	RSD	902:904	arg1	values					906:911	%RSD values	901:911	%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively	901:979	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	1	69	theme	titanium	158:165	arg1	dioxide					167:173	an on-line titanium dioxide	147:173	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	7	70	theme	Tryptic	1407:1413	arg1	digests					1415:1421	Tryptic digests	1407:1421	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP))	1407:1530	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	0	71	theme	extraction	64:73	arg1	spectrometry					106:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry	39:117	Analysis of glycopeptide biomarkers by on-line TiO2 solid-phase extraction capillary electrophoresis-mass spectrometry.
31892091	7	72	dep	CIII	1473:1476	arg1	i.e.					1447:1450	i.e.	1447:1450	i.e.	1447:1450	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
31892091	4	73	theme	%	901:901	arg1	values					906:911	%RSD values	901:911	%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively	901:979	Under the optimized conditions, the microcartridge lifetime was around 10 analyses and repeatability was acceptable (%RSD values of 9-11% and 6-11% for migration times and peak areas, respectively).
31892091	2	74	from	importance	471:480	arg1	control					493:499	quality control	485:499	quality control of biopharmaceuticals and doping analysis	485:541	The O126-glycopeptide of rhEPO was used to optimize the methodology given its importance in quality control of biopharmaceuticals and doping analysis.
31892091	1	75	theme	dioxide	167:173	arg1	method					259:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method	147:264	an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO)	147:390	In this study is described an on-line titanium dioxide solid-phase extraction capillary electrophoresis-mass spectrometry (TiO2-SPE-CE-MS) method for the analysis of the glycopeptide glycoforms obtained from the tryptic digests of recombinant human erythropoietin (rhEPO).
31892091	7	76	theme	different	1606:1614	arg1	composition					1623:1633	different glycan composition	1606:1633	different glycan composition	1606:1633	Tryptic digests of other glycoproteins (i.e. human apolipoprotein CIII (APO-C3) and bovine alpha-1-acid glycoprotein (bAGP)) were also analyzed, demonstrating the applicability to glycopeptides with different glycan composition and nature.
29553370	0	0	theme	frustrated	101:110	arg1	phagosomes					112:121	microbiostatic frustrated phagosomes	86:121	microbiostatic frustrated phagosomes	86:121	Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes.
29553370	4	1	theme	phagosomal	545:554	arg1	membranes					556:564	invaginating phagosomal membranes	532:564	invaginating phagosomal membranes	532:564	Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition.
29553370	0	2	theme	microbiostatic	86:99	arg1	phagosomes					112:121	microbiostatic frustrated phagosomes	86:121	microbiostatic frustrated phagosomes	86:121	Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes.
29553370	5	3	attach	present	631:637	arg1	plasmalemma					646:656	the plasmalemma	642:656	the plasmalemma	642:656	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	5	3	attach	present	631:637	arg2	P2					625:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	5	4	theme	phagosomal	687:696	arg1	membrane					698:705	the phagosomal membrane	683:705	the phagosomal membrane	683:705	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	7	5	theme	barrier	973:979	arg1	presence					949:956	the presence	945:956	the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma	945:1067	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	6	6	attach	present	852:858	arg1	membrane					883:890	the phagosomal membrane	868:890	the phagosomal membrane	868:890	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	6	6	attach	present	852:858	arg2	proteins					839:846	endo-lysosomal proteins	824:846	endo-lysosomal proteins	824:846	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	6	7	located	present	852:858	arg1	membrane					883:890	the phagosomal membrane	868:890	the phagosomal membrane	868:890	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	6	7	located	present	852:858	arg2	proteins					839:846	endo-lysosomal proteins	824:846	endo-lysosomal proteins	824:846	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	3	8	theme	F-actin	394:400	arg1	cuff					386:389	a thick cuff	378:389	a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan	378:487	These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan.
29553370	0	9	theme	phagosomes	112:121	arg1	formation					73:81	the formation	69:81	the formation of microbiostatic frustrated phagosomes	69:121	Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes.
29553370	5	10	from	membrane	804:811	arg1	absent					780:785	absent	780:785	absent	780:785	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	7	11	theme	phagosome	1029:1037	arg1	identity					1000:1007	the identity	996:1007	the identity of the open tubular phagosome separate from the plasmalemma	996:1067	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	7	12	theme	diffusion	963:971	arg1	barrier					973:979	a diffusion barrier	961:979	a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma	961:1067	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	2	13	theme	tubular	312:318	arg1	phagosomes					320:329	incompletely sealed tubular phagosomes	292:329	incompletely sealed tubular phagosomes	292:329	Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes.
29553370	6	14	from	membrane	883:890	arg1	present					852:858	present	852:858	present	852:858	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	4	15	theme	invaginating	532:543	arg1	membranes					556:564	invaginating phagosomal membranes	532:564	invaginating phagosomal membranes	532:564	Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition.
29553370	3	16	dep	activation	448:457	arg1	response					422:429	response	422:429	response	422:429	These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan.
29553370	2	17	theme	sealed	305:310	arg1	phagosomes					320:329	incompletely sealed tubular phagosomes	292:329	incompletely sealed tubular phagosomes	292:329	Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes.
29553370	0	18	theme	diffusion	15:23	arg1	barrier					25:31	Integrin-based diffusion barrier	0:31	Integrin-based diffusion barrier	0:31	Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes.
29553370	0	19	theme	Integrin-based	0:13	arg1	barrier					25:31	Integrin-based diffusion barrier	0:31	Integrin-based diffusion barrier	0:31	Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes.
29553370	5	20	from	detectable	669:678	arg1	membrane					698:705	the phagosomal membrane	683:705	the phagosomal membrane	683:705	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	3	21	theme	fungal	475:480	arg1	glycan					482:487	fungal glycan	475:487	fungal glycan	475:487	These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan.
29553370	5	22	theme	surface	796:802	arg1	membrane					804:811	the surface membrane	792:811	the surface membrane	792:811	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	9	23	theme	hyphae	1235:1240	arg1	growth					1221:1226	the growth	1217:1226	the growth of the hyphae	1217:1240	Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae.
29553370	1	24	theme	Candida	124:130	arg1	albicans					132:139	Candida albicans	124:139	Candida albicans hyphae	124:146	Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes.
29553370	7	25	from	plasmalemma	1057:1067	arg1	separate					1039:1046	separate	1039:1046	separate	1039:1046	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	8	26	theme	barrier	1088:1094	arg1	Formation					1070:1078	Formation	1070:1078	Formation of this barrier	1070:1094	Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly.
29553370	1	27	theme	albicans	132:139	arg1	hyphae					141:146	Candida albicans hyphae	124:146	Candida albicans hyphae	124:146	Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes.
29553370	6	28	theme	phagosomal	872:881	arg1	membrane					883:890	the phagosomal membrane	868:890	the phagosomal membrane	868:890	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	9	29	theme	Antimicrobial	1158:1170	arg1	mechanisms					1172:1181	Antimicrobial mechanisms	1158:1181	Antimicrobial mechanisms	1158:1181	Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae.
29553370	0	30	theme	membrane	43:50	arg1	domains					52:58	membrane domains	43:58	membrane domains enabling the formation of microbiostatic frustrated phagosomes	43:121	Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated phagosomes.
29553370	4	31	theme	distinct	586:593	arg1	composition					601:611	a strikingly distinct lipid composition	573:611	a strikingly distinct lipid composition	573:611	Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition.
29553370	3	32	theme	integrins	462:470	arg1	activation					448:457	non-canonical activation	434:457	non-canonical activation of integrins by fungal glycan	434:487	These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan.
29553370	7	33	theme	tubular	1021:1027	arg1	phagosome					1029:1037	the open tubular phagosome	1012:1037	the open tubular phagosome separate from the plasmalemma	1012:1067	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	3	34	theme	non-canonical	434:446	arg1	activation					448:457	non-canonical activation	434:457	non-canonical activation of integrins by fungal glycan	434:487	These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan.
29553370	5	35	from	membrane	698:705	arg1	detectable					669:678	detectable	669:678	detectable	669:678	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	8	36	theme	actin	1142:1146	arg1	assembly					1148:1155	formin-dependent actin assembly	1125:1155	formin-dependent actin assembly	1125:1155	Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly.
29553370	5	37	theme	PtdIns	614:619	arg1	P2					625:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	5	38	theme	PtdIns	729:734	arg1	P3					742:743	PtdIns(3,4,5)P3	729:743	PtdIns(3,4,5)P3	729:743	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	5	39	theme	PtdIns	714:719	arg1	P					723:723	PtdIns(3)P	714:723	PtdIns(3)P	714:723	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	4	40	theme	lipid	595:599	arg1	composition					601:611	a strikingly distinct lipid composition	573:611	a strikingly distinct lipid composition	573:611	Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition.
29553370	7	41	theme	separate	1039:1046	arg1	phagosome					1029:1037	the open tubular phagosome	1012:1037	the open tubular phagosome separate from the plasmalemma	1012:1067	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	6	42	theme	endo-lysosomal	824:837	arg1	proteins					839:846	endo-lysosomal proteins	824:846	endo-lysosomal proteins	824:846	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	5	43	theme	4,5	621:623	arg1	P2					625:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	3	44	theme	frustrated	338:347	arg1	phagosomes					349:358	These frustrated phagosomes	332:358	These frustrated phagosomes	332:358	These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan.
29553370	8	45	theme	formin-dependent	1125:1140	arg1	assembly					1148:1155	formin-dependent actin assembly	1125:1155	formin-dependent actin assembly	1125:1155	Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly.
29553370	1	46	theme	enormous	158:165	arg1	lengths					167:173	enormous lengths	158:173	enormous lengths	158:173	Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes.
29553370	7	47	theme	Fluorescence	893:904	arg1	recovery					906:913	Fluorescence recovery	893:913	Fluorescence recovery after photobleaching	893:934	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	7	48	theme	open	1016:1019	arg1	phagosome					1029:1037	the open tubular phagosome	1012:1037	the open tubular phagosome separate from the plasmalemma	1012:1067	Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma.
29553370	5	49	from	plasmalemma	646:656	arg1	present					631:637	present	631:637	present	631:637	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	3	50	theme	thick	380:384	arg1	cuff					386:389	a thick cuff	378:389	a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan	378:487	These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan.
29553370	2	51	theme	hypha	274:278	arg1	portion					259:265	a portion	257:265	a portion of the hypha	257:278	Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes.
29553370	5	52	located	present	631:637	arg1	plasmalemma					646:656	the plasmalemma	642:656	the plasmalemma	642:656	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	5	52	located	present	631:637	arg2	P2					625:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2	614:626	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
29553370	6	53	from	present	852:858	arg1	membrane					883:890	the phagosomal membrane	868:890	the phagosomal membrane	868:890	Moreover, endo-lysosomal proteins are present only in the phagosomal membrane.
29553370	5	54	theme	3,4,5	736:740	arg1	P3					742:743	PtdIns(3,4,5)P3	729:743	PtdIns(3,4,5)P3	729:743	PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane.
30938161	2	0	theme	acetonitrile	346:357	arg1	molecules					367:375	acetonitrile solvent molecules	346:375	acetonitrile solvent molecules	346:375	In the solid state, 1 forms a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules.
30938161	1	1	theme	solvatochromic	150:163	arg1	properties					165:174	solvatochromic properties	150:174	solvatochromic properties	150:174	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	4	2	theme	1	580:580	arg1	species					499:505	The species	495:505	The species responsible for this phenomenon	495:537	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	4	2	theme	1	580:580	arg1	form					572:575	the monodeprotonated betainic form	542:575	the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality	542:629	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	4	3	theme	responsible	507:517	arg1	species					499:505	The species	495:505	The species responsible for this phenomenon	495:537	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	4	3	theme	responsible	507:517	arg1	form					572:575	the monodeprotonated betainic form	542:575	the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality	542:629	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	2	4	theme	dimeric	264:270	arg1	assembly					272:279	a dimeric assembly	262:279	a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules	262:375	In the solid state, 1 forms a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules.
30938161	3	5	theme	TD-DFT	474:479	arg1	calculations					481:492	TD-DFT calculations	474:492	TD-DFT calculations	474:492	In solution, 1 shows a peculiar negative solvatochromism which was rationalized with the aid of TD-DFT calculations.
30938161	1	6	link	N-linked	181:188	arg1	derivative					220:229	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	1	7	dep	synthesis	106:114	arg1	the					102:104	the	102:104	the	102:104	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	3	8	theme	negative	410:417	arg1	solvatochromism					419:433	a peculiar negative solvatochromism	399:433	a peculiar negative solvatochromism which was rationalized with the aid of TD-DFT calculations	399:492	In solution, 1 shows a peculiar negative solvatochromism which was rationalized with the aid of TD-DFT calculations.
30938161	0	9	theme	Negative	0:7	arg1	Solvatochromism					9:23	Negative Solvatochromism	0:23	Negative Solvatochromism	0:23	Negative Solvatochromism in a N-Linked p-Pyridiniumcalix[4]arene Derivative.
30938161	4	10	theme	betainic	563:570	arg1	species					499:505	The species	495:505	The species responsible for this phenomenon	495:537	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	4	10	theme	betainic	563:570	arg1	form					572:575	the monodeprotonated betainic form	542:575	the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality	542:629	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	1	11	theme	N-linked	181:188	arg1	derivative					220:229	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	3	12	dep	the	463:465	arg1	aid					467:469	aid	467:469	aid	467:469	In solution, 1 shows a peculiar negative solvatochromism which was rationalized with the aid of TD-DFT calculations.
30938161	1	13	theme	p-pyridiniumcalix[4	190:208	arg1	derivative					220:229	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	0	14	theme	p-Pyridiniumcalix[4	39:57	arg1	Derivative					65:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	Negative Solvatochromism in a N-Linked p-Pyridiniumcalix[4]arene Derivative.
30938161	1	15	theme	arenediol	210:218	arg1	derivative					220:229	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	a N-linked p-pyridiniumcalix[4]arenediol derivative 1	179:231	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	0	16	theme	N-Linked	30:37	arg1	Derivative					65:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	Negative Solvatochromism in a N-Linked p-Pyridiniumcalix[4]arene Derivative.
30938161	3	17	theme	peculiar	401:408	arg1	solvatochromism					419:433	a peculiar negative solvatochromism	399:433	a peculiar negative solvatochromism which was rationalized with the aid of TD-DFT calculations	399:492	In solution, 1 shows a peculiar negative solvatochromism which was rationalized with the aid of TD-DFT calculations.
30938161	1	18	theme	derivative	220:229	arg1	properties					165:174	solvatochromic properties	150:174	solvatochromic properties	150:174	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	1	18	theme	derivative	220:229	arg1	synthesis					106:114	synthesis	106:114	synthesis	106:114	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	1	18	theme	derivative	220:229	arg1	characterization					128:143	structural characterization	117:143	structural characterization	117:143	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	0	19	theme	arene	59:63	arg1	Derivative					65:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	Negative Solvatochromism in a N-Linked p-Pyridiniumcalix[4]arene Derivative.
30938161	4	20	theme	monodeprotonated	546:561	arg1	species					499:505	The species	495:505	The species responsible for this phenomenon	495:537	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	4	20	theme	monodeprotonated	546:561	arg1	form					572:575	the monodeprotonated betainic form	542:575	the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality	542:629	The species responsible for this phenomenon is the monodeprotonated betainic form of 1 which is easily formed at pH close to neutrality.
30938161	2	21	theme	interactions	323:334	arg1	network					297:303	a network	295:303	a network of weak H-bonding interactions involving acetonitrile solvent molecules	295:375	In the solid state, 1 forms a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules.
30938161	2	22	theme	H-bonding	313:321	arg1	interactions					323:334	weak H-bonding interactions	308:334	weak H-bonding interactions involving acetonitrile solvent molecules	308:375	In the solid state, 1 forms a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules.
30938161	2	23	theme	weak	308:311	arg1	interactions					323:334	weak H-bonding interactions	308:334	weak H-bonding interactions involving acetonitrile solvent molecules	308:375	In the solid state, 1 forms a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules.
30938161	1	24	theme	structural	117:126	arg1	characterization					128:143	structural characterization	117:143	structural characterization	117:143	In this paper, we report the synthesis, structural characterization, and solvatochromic properties of a N-linked p-pyridiniumcalix[4]arenediol derivative 1.
30938161	0	25	dep	Solvatochromism	9:23	arg1	Derivative					65:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	a N-Linked p-Pyridiniumcalix[4]arene Derivative	28:74	Negative Solvatochromism in a N-Linked p-Pyridiniumcalix[4]arene Derivative.
30938161	2	26	theme	solid	241:245	arg1	state					247:251	the solid state	237:251	the solid state	237:251	In the solid state, 1 forms a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules.
30938161	2	27	theme	solvent	359:365	arg1	molecules					367:375	acetonitrile solvent molecules	346:375	acetonitrile solvent molecules	346:375	In the solid state, 1 forms a dimeric assembly stabilized by a network of weak H-bonding interactions involving acetonitrile solvent molecules.
30255241	2	0	contain	have	419:422	arg1	purification					322:333	purification	322:333	purification	322:333	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	0	contain	have	419:422	arg1	activities					350:359	biological activities	339:359	biological activities	339:359	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	0	contain	have	419:422	arg1	extraction					310:319	extraction	310:319	extraction	310:319	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	0	contain	have	419:422	arg2	meaning					436:442	significant meaning	424:442	significant meaning	424:442	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	9	1	theme	Bax-dependent	1923:1935	arg1	pathway					1937:1943	the Bcl-2 and Bax-dependent pathway	1909:1943	pathway	1937:1943	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	10	2	theme	Fractional	1958:1967	arg1	precipitation					1969:1981	CONCLUSIONS Fractional precipitation	1946:1981	CONCLUSIONS Fractional precipitation with ethanol	1946:1994	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	6	3	theme	HepG2	1349:1353	arg1	cells					1355:1359	HepG2 cells	1349:1359	HepG2 cells	1349:1359	Finally, the anticancer activities of them were investigated via the MTT assay and the western blot analysis using HepG2 cells.
30255241	3	4	theme	water	558:562	arg1	method					598:603	hot water extraction- ethanol precipitation method	554:603	hot water extraction- ethanol precipitation method	554:603	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	7	5	theme	molecular	1501:1509	arg1	weights					1511:1517	their average molecular weights	1487:1517	their average molecular weights	1487:1517	RESULTS Among these four purified fractions were mainly composed of D-mannose and D-glucose with different molar ratios, and their average molecular weights were 999, 657, 243 and 50.3 kDa, respectively.
30255241	8	6	theme	close	1692:1696	arg1	antioxidant					1698:1708	very close antioxidant	1687:1708	very close antioxidant	1687:1708	What's more, DOP-70 always exhibited the strongest antioxidant and anticancer activities, while DOP-40 and DOP-60 showed very close antioxidant and anticancer activities which were better than that of DOP-50.
30255241	3	7	theme	hot	554:556	arg1	method					598:603	hot water extraction- ethanol precipitation method	554:603	hot water extraction- ethanol precipitation method	554:603	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	6	8	theme	western	1321:1327	arg1	analysis					1334:1341	the western blot analysis	1317:1341	the western blot analysis using HepG2 cells	1317:1359	Finally, the anticancer activities of them were investigated via the MTT assay and the western blot analysis using HepG2 cells.
30255241	4	9	theme	purified	902:909	arg1	fractions					911:919	four purified fractions	897:919	four purified fractions	897:919	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	9	10	theme	western	1779:1785	arg1	analysis					1796:1803	The western blotting analysis	1775:1803	The western blotting analysis	1775:1803	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	10	11	theme	new	2037:2039	arg1	fractions					2056:2064	extract four new polysaccharide fractions	2024:2064	extract four new polysaccharide fractions from Dendrobium officinale stems	2024:2097	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	1	12	theme	traditional	224:234	arg1	herb					244:247	a precious traditional Chinese herb	213:247	a precious traditional Chinese herb	213:247	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb is widely used in medicines and health supplements.
30255241	7	13	theme	molar	1469:1473	arg1	ratios					1475:1480	different molar ratios	1459:1480	different molar ratios	1459:1480	RESULTS Among these four purified fractions were mainly composed of D-mannose and D-glucose with different molar ratios, and their average molecular weights were 999, 657, 243 and 50.3 kDa, respectively.
30255241	10	14	theme	extract	2024:2030	arg1	fractions					2056:2064	extract four new polysaccharide fractions	2024:2064	extract four new polysaccharide fractions from Dendrobium officinale stems	2024:2097	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	0	15	theme	cells	150:154	arg1	activities					156:165	their preliminary antioxidant and anti-HepG2 cells activities	105:165	their preliminary antioxidant and anti-HepG2 cells activities in vitro	105:174	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	3	16	theme	new	615:617	arg1	DOP-60					661:666	DOP-60	661:666	DOP-60	661:666	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	16	theme	new	615:617	arg1	DOP-70					673:678	DOP-70	673:678	DOP-70	673:678	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	16	theme	new	615:617	arg1	fractions					634:642	four new polysaccharide fractions	610:642	four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70)	610:679	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	4	17	theme	performance	996:1006	arg1	chromatography					1015:1028	high performance liquid chromatography	991:1028	high performance liquid chromatography	991:1028	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	10	18	with	precipitation	1969:1981	arg1	ethanol					1988:1994	ethanol	1988:1994	ethanol	1988:1994	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	10	19	theme	Dendrobium	2071:2080	arg1	stems					2093:2097	Dendrobium officinale stems	2071:2097	Dendrobium officinale stems	2071:2097	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	4	20	theme	performance	945:955	arg1	chromatography					972:985	high performance anion exchange chromatography	940:985	high performance anion exchange chromatography	940:985	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	9	21	theme	blotting	1787:1794	arg1	analysis					1796:1803	The western blotting analysis	1775:1803	The western blotting analysis	1775:1803	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	2	22	from	extraction	310:319	arg1	stem					389:392	the stem	385:392	the stem of Dendrobium officinale	385:417	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	4	23	theme	exchange	963:970	arg1	chromatography					972:985	high performance anion exchange chromatography	940:985	high performance anion exchange chromatography	940:985	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	5	24	theme	superoxide	1118:1127	arg1	anion					1129:1133	the superoxide anion	1114:1133	the superoxide anion	1114:1133	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	2	25	from	purification	322:333	arg1	stem					389:392	the stem	385:392	the stem of Dendrobium officinale	385:417	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	6	26	theme	them	1272:1275	arg1	activities					1258:1267	the anticancer activities	1243:1267	the anticancer activities of them	1243:1275	Finally, the anticancer activities of them were investigated via the MTT assay and the western blot analysis using HepG2 cells.
30255241	2	27	dep	extraction	310:319	arg1	the					306:308	the	306:308	the	306:308	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	3	28	theme	gel	831:833	arg1	resin					835:839	Toyopearl-H65F gel resin	816:839	Toyopearl-H65F gel resin	816:839	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	0	29	theme	fractional	76:85	arg1	precipitation					87:99	fractional precipitation	76:99	fractional precipitation	76:99	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	5	30	theme	free	1187:1190	arg1	radicals					1192:1199	hydroxyl free radicals	1178:1199	hydroxyl free radicals	1178:1199	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	1	31	theme	BACKGROUND	177:186	arg1	officinale					199:208	BACKGROUND Dendrobium officinale	177:208	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb	177:247	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb is widely used in medicines and health supplements.
30255241	7	32	with	D-mannose	1430:1438	arg1	ratios					1475:1480	different molar ratios	1459:1480	different molar ratios	1459:1480	RESULTS Among these four purified fractions were mainly composed of D-mannose and D-glucose with different molar ratios, and their average molecular weights were 999, 657, 243 and 50.3 kDa, respectively.
30255241	5	33	theme	scavenging	1201:1210	arg1	assays					1212:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	3	34	dep	fractions	634:642	arg1	DOP-60					661:666	DOP-60	661:666	DOP-60	661:666	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	34	dep	fractions	634:642	arg1	DOP-70					673:678	DOP-70	673:678	DOP-70	673:678	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	34	dep	fractions	634:642	arg1	fractions					634:642	four new polysaccharide fractions	610:642	four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70)	610:679	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	10	35	theme	polysaccharide	2108:2121	arg1	fractions					2123:2131	the polysaccharide fractions	2104:2131	the polysaccharide fractions	2104:2131	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	0	36	theme	preliminary	111:121	arg1	antioxidant					123:133	their preliminary antioxidant	105:133	their preliminary antioxidant	105:133	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	0	37	from	officinale	62:71	arg1	polysaccharides					30:44	polysaccharides	30:44	polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro	30:174	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	0	37	from	officinale	62:71	arg1	properties					16:25	Physicochemical properties	0:25	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.	0:175	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	3	38	theme	crude	489:493	arg1	polysaccharide					517:530	The crude Dendrobium officinale polysaccharide	485:530	METHODS The crude Dendrobium officinale polysaccharide (DOP)	477:536	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	38	theme	crude	489:493	arg1	DOP					533:535	DOP	533:535	DOP	533:535	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	5	39	theme	them	1061:1064	arg1	activities					1047:1056	The antioxidant activities	1031:1056	The antioxidant activities of them	1031:1064	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	0	40	theme	Physicochemical	0:14	arg1	properties					16:25	Physicochemical properties	0:25	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.	0:175	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	7	41	theme	purified	1387:1394	arg1	fractions					1396:1404	these four purified fractions	1376:1404	these four purified fractions	1376:1404	RESULTS Among these four purified fractions were mainly composed of D-mannose and D-glucose with different molar ratios, and their average molecular weights were 999, 657, 243 and 50.3 kDa, respectively.
30255241	10	42	contain	possessed	2133:2141	arg2	DOP-70					2203:2208	DOP-70	2203:2208	DOP-70	2203:2208	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	10	42	contain	possessed	2133:2141	arg1	fractions					2123:2131	the polysaccharide fractions	2104:2131	the polysaccharide fractions	2104:2131	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	10	42	contain	possessed	2133:2141	arg2	activities					2180:2189	anticancer activities	2169:2189	anticancer activities	2169:2189	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	10	42	contain	possessed	2133:2141	arg2	antioxidant					2153:2163	efficient antioxidant	2143:2163	efficient antioxidant	2143:2163	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	3	43	dep	METHODS	477:483	arg1	polysaccharide					517:530	The crude Dendrobium officinale polysaccharide	485:530	METHODS The crude Dendrobium officinale polysaccharide (DOP)	477:536	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	43	dep	METHODS	477:483	arg1	DOP					533:535	DOP	533:535	DOP	533:535	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	9	44	theme	HepG2	1870:1874	arg1	cells					1895:1899	HepG2 human liver cancer cells	1870:1899	HepG2 human liver cancer cells	1870:1899	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	3	45	theme	officinale	506:515	arg1	polysaccharide					517:530	The crude Dendrobium officinale polysaccharide	485:530	METHODS The crude Dendrobium officinale polysaccharide (DOP)	477:536	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	45	theme	officinale	506:515	arg1	DOP					533:535	DOP	533:535	DOP	533:535	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	5	46	theme	power	1097:1101	arg1	assay					1103:1107	the reducing power assay	1084:1107	the reducing power assay	1084:1107	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	9	47	theme	liver	1882:1886	arg1	cells					1895:1899	HepG2 human liver cancer cells	1870:1899	HepG2 human liver cancer cells	1870:1899	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	8	48	theme	antioxidant	1617:1627	arg1	activities					1644:1653	antioxidant and anticancer activities	1617:1653	the strongest antioxidant and anticancer activities	1603:1653	What's more, DOP-70 always exhibited the strongest antioxidant and anticancer activities, while DOP-40 and DOP-60 showed very close antioxidant and anticancer activities which were better than that of DOP-50.
30255241	4	49	theme	monosaccharide	867:880	arg1	composition					882:892	monosaccharide composition	867:892	monosaccharide composition	867:892	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	10	50	theme	anticancer	2169:2178	arg1	activities					2180:2189	anticancer activities	2169:2189	anticancer activities	2169:2189	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	8	51	theme	anticancer	1633:1642	arg1	activities					1644:1653	antioxidant and anticancer activities	1617:1653	the strongest antioxidant and anticancer activities	1603:1653	What's more, DOP-70 always exhibited the strongest antioxidant and anticancer activities, while DOP-40 and DOP-60 showed very close antioxidant and anticancer activities which were better than that of DOP-50.
30255241	3	52	theme	crude	712:716	arg1	DOP					718:720	the crude DOP	708:720	the crude DOP	708:720	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	2	53	dep	theory	447:452	arg1	value					470:474	value	470:474	value	470:474	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	3	54	theme	extraction-	564:574	arg1	method					598:603	hot water extraction- ethanol precipitation method	554:603	hot water extraction- ethanol precipitation method	554:603	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	8	55	theme	anticancer	1714:1723	arg1	activities					1725:1734	anticancer activities	1714:1734	anticancer activities	1714:1734	What's more, DOP-70 always exhibited the strongest antioxidant and anticancer activities, while DOP-40 and DOP-60 showed very close antioxidant and anticancer activities which were better than that of DOP-50.
30255241	8	56	dep	more	1573:1576	arg1	's					1570:1571	's	1570:1571	's	1570:1571	What's more, DOP-70 always exhibited the strongest antioxidant and anticancer activities, while DOP-40 and DOP-60 showed very close antioxidant and anticancer activities which were better than that of DOP-50.
30255241	10	57	theme	officinale	2082:2091	arg1	stems					2093:2097	Dendrobium officinale stems	2071:2097	Dendrobium officinale stems	2071:2097	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	2	58	theme	Dendrobium	397:406	arg1	officinale					408:417	Dendrobium officinale	397:417	Dendrobium officinale	397:417	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	1	59	theme	health	281:286	arg1	supplements					288:298	health supplements	281:298	health supplements	281:298	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb is widely used in medicines and health supplements.
30255241	4	60	theme	fractions	911:919	arg1	weight					856:861	molecular weight	846:861	molecular weight	846:861	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	4	60	theme	fractions	911:919	arg1	composition					882:892	monosaccharide composition	867:892	monosaccharide composition	867:892	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	10	61	theme	CONCLUSIONS	1946:1956	arg1	precipitation					1969:1981	CONCLUSIONS Fractional precipitation	1946:1981	CONCLUSIONS Fractional precipitation with ethanol	1946:1994	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	3	62	with	precipitation	736:748	arg1	method					763:768	ethanol method	755:768	ethanol method	755:768	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	2	63	from	stem	389:392	arg1	polysaccharides					364:378	polysaccharides	364:378	polysaccharides from the stem of Dendrobium officinale	364:417	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	63	from	stem	389:392	arg1	purification					322:333	purification	322:333	purification	322:333	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	63	from	stem	389:392	arg1	activities					350:359	biological activities	339:359	biological activities	339:359	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	63	from	stem	389:392	arg1	extraction					310:319	extraction	310:319	extraction	310:319	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	6	64	theme	anticancer	1247:1256	arg1	activities					1258:1267	the anticancer activities	1243:1267	the anticancer activities of them	1243:1275	Finally, the anticancer activities of them were investigated via the MTT assay and the western blot analysis using HepG2 cells.
30255241	6	65	theme	blot	1329:1332	arg1	analysis					1334:1341	the western blot analysis	1317:1341	the western blot analysis using HepG2 cells	1317:1359	Finally, the anticancer activities of them were investigated via the MTT assay and the western blot analysis using HepG2 cells.
30255241	3	66	theme	precipitation	584:596	arg1	method					598:603	hot water extraction- ethanol precipitation method	554:603	hot water extraction- ethanol precipitation method	554:603	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	9	67	theme	cancer	1888:1893	arg1	cells					1895:1899	HepG2 human liver cancer cells	1870:1899	HepG2 human liver cancer cells	1870:1899	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	7	68	theme	average	1493:1499	arg1	weights					1511:1517	their average molecular weights	1487:1517	their average molecular weights	1487:1517	RESULTS Among these four purified fractions were mainly composed of D-mannose and D-glucose with different molar ratios, and their average molecular weights were 999, 657, 243 and 50.3 kDa, respectively.
30255241	3	69	theme	ethanol	755:761	arg1	method					763:768	ethanol method	755:768	ethanol method	755:768	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	70	theme	polysaccharide	619:632	arg1	DOP-60					661:666	DOP-60	661:666	DOP-60	661:666	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	70	theme	polysaccharide	619:632	arg1	DOP-70					673:678	DOP-70	673:678	DOP-70	673:678	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	70	theme	polysaccharide	619:632	arg1	fractions					634:642	four new polysaccharide fractions	610:642	four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70)	610:679	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	1	71	theme	precious	215:222	arg1	herb					244:247	a precious traditional Chinese herb	213:247	a precious traditional Chinese herb	213:247	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb is widely used in medicines and health supplements.
30255241	2	72	theme	biological	339:348	arg1	activities					350:359	biological activities	339:359	biological activities	339:359	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	1	73	theme	Chinese	236:242	arg1	herb					244:247	a precious traditional Chinese herb	213:247	a precious traditional Chinese herb	213:247	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb is widely used in medicines and health supplements.
30255241	5	74	theme	2,2-diphenyl-1-picrylhydrazyl	1136:1164	arg1	assays					1212:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	4	75	dep	weight	856:861	arg1	The					842:844	The	842:844	The	842:844	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	4	76	theme	high	991:994	arg1	chromatography					1015:1028	high performance liquid chromatography	991:1028	high performance liquid chromatography	991:1028	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	7	77	theme	different	1459:1467	arg1	ratios					1475:1480	different molar ratios	1459:1480	different molar ratios	1459:1480	RESULTS Among these four purified fractions were mainly composed of D-mannose and D-glucose with different molar ratios, and their average molecular weights were 999, 657, 243 and 50.3 kDa, respectively.
30255241	3	78	theme	Toyopearl-H65F	816:829	arg1	resin					835:839	Toyopearl-H65F gel resin	816:839	Toyopearl-H65F gel resin	816:839	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	4	79	theme	high	940:943	arg1	chromatography					972:985	high performance anion exchange chromatography	940:985	high performance anion exchange chromatography	940:985	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	10	80	theme	polysaccharide	2041:2054	arg1	fractions					2056:2064	extract four new polysaccharide fractions	2024:2064	extract four new polysaccharide fractions from Dendrobium officinale stems	2024:2097	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	4	81	theme	anion	957:961	arg1	chromatography					972:985	high performance anion exchange chromatography	940:985	high performance anion exchange chromatography	940:985	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	5	82	theme	anion	1129:1133	arg1	assays					1212:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	7	83	with	D-glucose	1444:1452	arg1	ratios					1475:1480	different molar ratios	1459:1480	different molar ratios	1459:1480	RESULTS Among these four purified fractions were mainly composed of D-mannose and D-glucose with different molar ratios, and their average molecular weights were 999, 657, 243 and 50.3 kDa, respectively.
30255241	5	84	theme	radicals	1192:1199	arg1	assays					1212:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays	1114:1217	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	1	85	theme	Dendrobium	188:197	arg1	officinale					199:208	BACKGROUND Dendrobium officinale	177:208	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb	177:247	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb is widely used in medicines and health supplements.
30255241	0	86	from	properties	16:25	arg1	officinale					62:71	Dendrobium officinale	51:71	Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro	51:174	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	0	87	theme	antioxidant	123:133	arg1	activities					156:165	their preliminary antioxidant and anti-HepG2 cells activities	105:165	their preliminary antioxidant and anti-HepG2 cells activities in vitro	105:174	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	5	88	theme	antioxidant	1035:1045	arg1	activities					1047:1056	The antioxidant activities	1031:1056	The antioxidant activities of them	1031:1064	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	2	89	from	activities	350:359	arg1	stem					389:392	the stem	385:392	the stem of Dendrobium officinale	385:417	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	4	90	theme	liquid	1008:1013	arg1	chromatography					1015:1028	high performance liquid chromatography	991:1028	high performance liquid chromatography	991:1028	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	0	91	theme	anti-HepG2	139:148	arg1	cells					150:154	anti-HepG2 cells	139:154	anti-HepG2 cells	139:154	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	3	92	theme	Dendrobium	495:504	arg1	polysaccharide					517:530	The crude Dendrobium officinale polysaccharide	485:530	METHODS The crude Dendrobium officinale polysaccharide (DOP)	477:536	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	92	theme	Dendrobium	495:504	arg1	DOP					533:535	DOP	533:535	DOP	533:535	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	5	93	theme	hydroxyl	1178:1185	arg1	radicals					1192:1199	hydroxyl free radicals	1178:1199	hydroxyl free radicals	1178:1199	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	2	94	theme	significant	424:434	arg1	meaning					436:442	significant meaning	424:442	significant meaning	424:442	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	0	95	theme	polysaccharides	30:44	arg1	properties					16:25	Physicochemical properties	0:25	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.	0:175	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	10	96	from	stems	2093:2097	arg1	fractions					2056:2064	extract four new polysaccharide fractions	2024:2064	extract four new polysaccharide fractions from Dendrobium officinale stems	2024:2097	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	8	97	theme	strongest	1607:1615	arg1	activities					1644:1653	antioxidant and anticancer activities	1617:1653	the strongest antioxidant and anticancer activities	1603:1653	What's more, DOP-70 always exhibited the strongest antioxidant and anticancer activities, while DOP-40 and DOP-60 showed very close antioxidant and anticancer activities which were better than that of DOP-50.
30255241	0	98	theme	Dendrobium	51:60	arg1	officinale					62:71	Dendrobium officinale	51:71	Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro	51:174	Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro.
30255241	5	99	theme	reducing	1088:1095	arg1	assay					1103:1107	the reducing power assay	1084:1107	the reducing power assay	1084:1107	The antioxidant activities of them were evaluated by the reducing power assay, and the superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and hydroxyl free radicals scavenging assays, respectively.
30255241	10	100	theme	efficient	2143:2151	arg1	antioxidant					2153:2163	efficient antioxidant	2143:2163	efficient antioxidant	2143:2163	CONCLUSIONS Fractional precipitation with ethanol could successfully apply to extract four new polysaccharide fractions from Dendrobium officinale stems, and the polysaccharide fractions possessed efficient antioxidant and anticancer activities, especially DOP-70.
30255241	9	101	theme	human	1876:1880	arg1	cells					1895:1899	HepG2 human liver cancer cells	1870:1899	HepG2 human liver cancer cells	1870:1899	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	4	102	theme	molecular	846:854	arg1	weight					856:861	molecular weight	846:861	molecular weight	846:861	The molecular weight and monosaccharide composition of four purified fractions were determined by high performance anion exchange chromatography and high performance liquid chromatography.
30255241	2	103	theme	officinale	408:417	arg1	stem					389:392	the stem	385:392	the stem of Dendrobium officinale	385:417	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	6	104	theme	MTT	1303:1305	arg1	assay					1307:1311	the MTT assay	1299:1311	the MTT assay	1299:1311	Finally, the anticancer activities of them were investigated via the MTT assay and the western blot analysis using HepG2 cells.
30255241	2	105	theme	polysaccharides	364:378	arg1	purification					322:333	purification	322:333	purification	322:333	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	105	theme	polysaccharides	364:378	arg1	activities					350:359	biological activities	339:359	biological activities	339:359	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	2	105	theme	polysaccharides	364:378	arg1	extraction					310:319	extraction	310:319	extraction	310:319	Thus the extraction, purification and biological activities of polysaccharides from the stem of Dendrobium officinale have significant meaning on theory and application value.
30255241	1	106	used	used	259:262	arg2	officinale					199:208	BACKGROUND Dendrobium officinale	177:208	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb	177:247	BACKGROUND Dendrobium officinale as a precious traditional Chinese herb is widely used in medicines and health supplements.
30255241	9	107	theme	Bcl-2	1913:1917	arg1	pathway					1937:1943	the Bcl-2 and Bax-dependent pathway	1909:1943	pathway	1937:1943	The western blotting analysis also showed that DOP-40, DOP-60, and DOP-70 induced apoptosis in HepG2 human liver cancer cells through the Bcl-2 and Bax-dependent pathway.
30255241	3	108	theme	fractional	725:734	arg1	precipitation					736:748	fractional precipitation	725:748	fractional precipitation with ethanol method	725:768	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30255241	3	109	theme	ethanol	576:582	arg1	method					598:603	hot water extraction- ethanol precipitation method	554:603	hot water extraction- ethanol precipitation method	554:603	METHODS The crude Dendrobium officinale polysaccharide (DOP) was obtained by hot water extraction- ethanol precipitation method, and four new polysaccharide fractions (DOP-40, DOP-50, DOP-60, and DOP-70) were further obtained from the crude DOP by fractional precipitation with ethanol method, then four fractions were further purified by Toyopearl-H65F gel resin.
30721968	7	0	theme	wrestler	1288:1295	arg1	MC4R					1312:1315	MC4R	1312:1315	MC4R	1312:1315	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	0	theme	wrestler	1288:1295	arg1	FTO					1304:1306	FTO	1304:1306	FTO	1304:1306	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	0	theme	wrestler	1288:1295	arg1	loci					1298:1301	"sumo wrestler" loci	1282:1301	"sumo wrestler" loci (FTO and MC4R)	1282:1316	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	5	1	dep	adjustments	751:761	arg1	adjustment					779:788	Model 1 no fat adjustment	764:788	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	3	2	contain	having	290:295	arg1	signals					282:288	genetic signals	274:288	genetic signals having an association with both lean mass and fat mass	274:343	Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.
30721968	3	2	contain	having	290:295	arg2	association					300:310	an association	297:310	an association with both lean mass and fat mass	297:343	Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.
30721968	9	3	theme	SNPs	1626:1629	arg1	alleles					1615:1621	LM increasing alleles	1601:1621	LM increasing alleles of SNPs in "body builder" loci	1601:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	8	4	theme	body	1384:1387	arg1	VCAN					1404:1407	VCAN	1404:1407	VCAN	1404:1407	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	4	theme	body	1384:1387	arg1	loci					1398:1401	body builder" loci	1384:1401	body builder" loci (VCAN and ADAMTSL3)	1384:1421	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	4	theme	body	1384:1387	arg1	ADAMTSL3					1413:1420	ADAMTSL3	1413:1420	ADAMTSL3	1413:1420	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	7	5	dep	loci	1298:1301	arg1	MC4R					1312:1315	MC4R	1312:1315	MC4R	1312:1315	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	5	dep	loci	1298:1301	arg1	FTO					1304:1306	FTO	1304:1306	FTO	1304:1306	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	5	dep	loci	1298:1301	arg1	loci					1298:1301	"sumo wrestler" loci	1282:1301	"sumo wrestler" loci (FTO and MC4R)	1282:1316	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	6	theme	same	1245:1248	arg1	direction					1250:1258	the same direction	1241:1258	the same direction	1241:1258	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	8	7	theme	"	1396:1396	arg1	VCAN					1404:1407	VCAN	1404:1407	VCAN	1404:1407	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	7	theme	"	1396:1396	arg1	loci					1398:1401	body builder" loci	1384:1401	body builder" loci (VCAN and ADAMTSL3)	1384:1421	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	7	theme	"	1396:1396	arg1	ADAMTSL3					1413:1420	ADAMTSL3	1413:1420	ADAMTSL3	1413:1420	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	5	8	theme	X-ray	627:631	arg1	absorptiometry					633:646	dual-energy X-ray absorptiometry	615:646	dual-energy X-ray absorptiometry	615:646	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	11	9	theme	harmful	1858:1864	arg1	effects					1880:1886	either harmful or protective effects	1851:1886	either harmful or protective effects	1851:1886	Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
30721968	7	10	from	associations	1122:1133	arg1	Model					1138:1142	Model 1	1138:1144	Model 1	1138:1144	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	10	from	associations	1122:1133	arg1	Model					1149:1153	Model 3	1149:1155	Model 3	1149:1155	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	9	11	theme	builder	1640:1646	arg1	loci					1649:1652	"body builder" loci	1634:1652	"body builder" loci	1634:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	8	12	from	impact	1345:1350	arg1	LM					1368:1369	LM	1368:1369	LM	1368:1369	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	5	13	from	mass	880:883	arg1	kilograms					888:896	kilograms	888:896	kilograms	888:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	7	14	from	Model	1138:1142	arg1	strengths					1105:1113	the strengths	1101:1113	the strengths of the associations in Model 1 vs Model 3	1101:1155	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	15	theme	fat	1229:1231	arg1	mass					1233:1236	fat mass	1229:1236	fat mass	1229:1236	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	9	16	theme	existing	1430:1437	arg1	databases					1479:1487	existing available genome-wide association study databases	1430:1487	existing available genome-wide association study databases	1430:1487	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	9	17	theme	genome-wide	1449:1459	arg1	databases					1479:1487	existing available genome-wide association study databases	1430:1487	existing available genome-wide association study databases	1430:1487	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	4	18	theme	fat	394:396	arg1	adjustments					403:413	different fat mass adjustments	384:413	different fat mass adjustments	384:413	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	3	19	with	association	300:310	arg1	mass					327:330	lean mass	322:330	lean mass	322:330	Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.
30721968	3	19	with	association	300:310	arg1	mass					340:343	fat mass	336:343	fat mass	336:343	Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.
30721968	9	20	theme	metabolic	1675:1683	arg1	protection					1685:1694	metabolic protection	1675:1694	metabolic protection	1675:1694	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	2	21	theme	fat	199:201	arg1	mass					203:206	fat mass	199:206	fat mass in kilograms	199:219	We previously identified five loci associated with LM adjusted for fat mass in kilograms.
30721968	5	22	theme	fat	775:777	arg1	adjustment					779:788	Model 1 no fat adjustment	764:788	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	9	23	theme	study	1473:1477	arg1	databases					1479:1487	existing available genome-wide association study databases	1430:1487	existing available genome-wide association study databases	1430:1487	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	4	24	theme	adjustments	403:413	arg1	impact					374:379	the impact	370:379	the impact of different fat mass adjustments on genetic architecture of LM	370:443	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	5	25	theme	association	511:521	arg1	analyses					523:530	genome-wide association analyses	499:530	genome-wide association analyses	499:530	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	26	with	cohorts	554:560	arg1	n = 38,292					588:597	n = 38,292	588:597	n = 38,292	588:597	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	27	theme	bioelectrical	652:664	arg1	analysis					676:683	bioelectrical impedance analysis	652:683	bioelectrical impedance analysis	652:683	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	6	28	theme	47,227	1056:1061	arg1	individuals					1063:1073	an additional 47,227 individuals	1042:1073	an additional 47,227 individuals from 29 cohorts	1042:1089	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	9	29	theme	increasing	1493:1502	arg1	alleles					1504:1510	LM increasing alleles	1490:1510	LM increasing alleles of SNPs in sumo wrestler loci	1490:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	10	30	theme	novel	1742:1746	arg1	TNRC6B					1758:1763	TNRC6B	1758:1763	TNRC6B	1758:1763	Conclusions In conclusion, we identified one novel LM locus (TNRC6B).
30721968	10	30	theme	novel	1742:1746	arg1	locus					1751:1755	one novel LM locus	1738:1755	one novel LM locus (TNRC6B)	1738:1764	Conclusions In conclusion, we identified one novel LM locus (TNRC6B).
30721968	1	31	theme	metabolic	112:120	arg1	function					122:129	metabolic function	112:129	metabolic function	112:129	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	3	32	theme	genetic	274:280	arg1	signals					282:288	genetic signals	274:288	genetic signals having an association with both lean mass and fat mass	274:343	Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.
30721968	8	33	dep	loci	1398:1401	arg1	VCAN					1404:1407	VCAN	1404:1407	VCAN	1404:1407	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	33	dep	loci	1398:1401	arg1	loci					1398:1401	body builder" loci	1384:1401	body builder" loci (VCAN and ADAMTSL3)	1384:1421	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	33	dep	loci	1398:1401	arg1	ADAMTSL3					1413:1420	ADAMTSL3	1413:1420	ADAMTSL3	1413:1420	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	9	34	dep	associated	1547:1556	arg1	whereas					1593:1599	whereas	1593:1599	whereas	1593:1599	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	4	35	theme	additional	458:467	arg1	loci					472:475	additional LM loci	458:475	additional LM loci	458:475	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	1	36	theme	body	57:60	arg1	mass					62:65	Background Lean body mass	41:65	Background Lean body mass (LM)	41:70	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	1	36	theme	body	57:60	arg1	LM					68:69	LM	68:69	LM	68:69	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	9	37	theme	wrestler	1528:1535	arg1	loci					1537:1540	sumo wrestler loci	1523:1540	sumo wrestler loci	1523:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	4	38	theme	genetic	418:424	arg1	architecture					426:437	genetic architecture	418:437	genetic architecture of LM	418:443	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	5	39	theme	fat	876:878	arg1	mass					880:883	fat mass	876:883	fat mass in kilograms	876:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	2	40	from	mass	203:206	arg1	kilograms					211:219	kilograms	211:219	kilograms	211:219	We previously identified five loci associated with LM adjusted for fat mass in kilograms.
30721968	3	41	theme	fat	336:338	arg1	mass					340:343	fat mass	336:343	fat mass	336:343	Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.
30721968	10	42	dep	Conclusions	1697:1707	arg1	conclusion					1712:1721	conclusion	1712:1721	conclusion	1712:1721	Conclusions In conclusion, we identified one novel LM locus (TNRC6B).
30721968	5	43	theme	mass	746:749	arg1	adjustments					751:761	fat mass adjustments	742:761	fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms)	742:897	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	44	theme	mass	847:850	arg1	percentage					828:837	a percentage	826:837	a percentage of body mass	826:850	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	7	45	from	effect	1200:1205	arg1	mass					1220:1223	lean mass	1215:1223	lean mass	1215:1223	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	45	from	effect	1200:1205	arg1	mass					1233:1236	fat mass	1229:1236	fat mass	1229:1236	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	45	from	effect	1200:1205	arg1	direction					1250:1258	the same direction	1241:1258	the same direction	1241:1258	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	11	46	theme	protective	1869:1878	arg1	effects					1880:1886	either harmful or protective effects	1851:1886	either harmful or protective effects	1851:1886	Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
30721968	5	47	theme	Model	853:857	arg1	adjustment					861:870	Model 3 adjustment	853:870	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	9	48	theme	adverse	1566:1572	arg1	profile					1584:1590	an adverse metabolic profile	1563:1590	an adverse metabolic profile	1563:1590	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	0	49	theme	lean	30:33	arg1	mass					35:38	lean mass	30:38	lean mass	30:38	Disentangling the genetics of lean mass.
30721968	7	50	from	Model	1149:1153	arg1	strengths					1105:1113	the strengths	1101:1113	the strengths of the associations in Model 1 vs Model 3	1101:1155	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	5	51	dep	adjustment	779:788	arg1	adjustment					861:870	Model 3 adjustment	853:870	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	51	dep	adjustment	779:788	arg1	adjustment					799:808	Model 2 adjustment	791:808	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	7	52	theme	"	1296:1296	arg1	MC4R					1312:1315	MC4R	1312:1315	MC4R	1312:1315	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	52	theme	"	1296:1296	arg1	FTO					1304:1306	FTO	1304:1306	FTO	1304:1306	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	52	theme	"	1296:1296	arg1	loci					1298:1301	"sumo wrestler" loci	1282:1301	"sumo wrestler" loci (FTO and MC4R)	1282:1316	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	9	53	theme	increasing	1604:1613	arg1	alleles					1615:1621	LM increasing alleles	1601:1621	LM increasing alleles of SNPs in "body builder" loci	1601:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	7	54	theme	sumo	1283:1286	arg1	MC4R					1312:1315	MC4R	1312:1315	MC4R	1312:1315	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	54	theme	sumo	1283:1286	arg1	FTO					1304:1306	FTO	1304:1306	FTO	1304:1306	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	54	theme	sumo	1283:1286	arg1	loci					1298:1301	"sumo wrestler" loci	1282:1301	"sumo wrestler" loci (FTO and MC4R)	1282:1316	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	1	55	theme	Background	41:50	arg1	mass					62:65	Background Lean body mass	41:65	Background Lean body mass (LM)	41:70	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	1	55	theme	Background	41:50	arg1	LM					68:69	LM	68:69	LM	68:69	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	7	56	theme	associations	1122:1133	arg1	strengths					1105:1113	the strengths	1101:1113	the strengths of the associations in Model 1 vs Model 3	1101:1155	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	5	57	dep	LM	547:548	arg1	measured					600:607	measured	600:607	measured using dual-energy X-ray absorptiometry	600:646	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	7	58	from	strengths	1105:1113	arg1	Model					1138:1142	Model 1	1138:1144	Model 1	1138:1144	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	7	58	from	strengths	1105:1113	arg1	Model					1149:1153	Model 3	1149:1155	Model 3	1149:1155	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	5	59	theme	dual-energy	615:625	arg1	absorptiometry					633:646	dual-energy X-ray absorptiometry	615:646	dual-energy X-ray absorptiometry	615:646	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	11	60	theme	lean	1829:1832	arg1	mass					1834:1837	lean mass	1829:1837	lean mass	1829:1837	Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
30721968	6	61	theme	additional	1045:1054	arg1	individuals					1063:1073	an additional 47,227 individuals	1042:1073	an additional 47,227 individuals from 29 cohorts	1042:1089	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	9	62	theme	body	1635:1638	arg1	loci					1649:1652	"body builder" loci	1634:1652	"body builder" loci	1634:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	8	63	theme	builder	1389:1395	arg1	VCAN					1404:1407	VCAN	1404:1407	VCAN	1404:1407	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	63	theme	builder	1389:1395	arg1	loci					1398:1401	body builder" loci	1384:1401	body builder" loci (VCAN and ADAMTSL3)	1384:1421	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	8	63	theme	builder	1389:1395	arg1	ADAMTSL3					1413:1420	ADAMTSL3	1413:1420	ADAMTSL3	1413:1420	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	5	64	theme	ancestry	574:581	arg1	cohorts					554:560	20 cohorts	551:560	20 cohorts of European ancestry with n = 38,292	551:597	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	9	65	from	SNPs	1626:1629	arg1	loci					1649:1652	"body builder" loci	1634:1652	"body builder" loci	1634:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	9	66	theme	"	1647:1647	arg1	loci					1649:1652	"body builder" loci	1634:1652	"body builder" loci	1634:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	6	67	from	polymorphisms	932:944	arg1	loci					965:968	separate loci	956:968	separate loci	956:968	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	6	67	from	polymorphisms	932:944	arg1	locus					994:998	one novel LM locus	981:998	one novel LM locus (TNRC6B)	981:1007	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	5	68	theme	Model	791:795	arg1	adjustment					799:808	Model 2 adjustment	791:808	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	9	69	from	alleles	1615:1621	arg1	loci					1649:1652	"body builder" loci	1634:1652	"body builder" loci	1634:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	5	70	dep	Methods	478:484	arg1	performed					489:497	performed	489:497	performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms)	489:897	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	71	theme	impedance	666:674	arg1	analysis					676:683	bioelectrical impedance analysis	652:683	bioelectrical impedance analysis	652:683	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	72	theme	Model	764:768	arg1	adjustment					779:788	Model 1 no fat adjustment	764:788	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	9	73	theme	available	1439:1447	arg1	databases					1479:1487	existing available genome-wide association study databases	1430:1487	existing available genome-wide association study databases	1430:1487	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	4	74	theme	mass	398:401	arg1	adjustments					403:413	different fat mass adjustments	384:413	different fat mass adjustments	384:413	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	8	75	with	loci	1332:1335	arg1	impact					1345:1350	an impact	1342:1350	an impact specifically on LM	1342:1369	In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3).
30721968	5	76	theme	no	772:773	arg1	adjustment					779:788	Model 1 no fat adjustment	764:788	Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms	764:896	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	9	77	theme	association	1461:1471	arg1	databases					1479:1487	existing available genome-wide association study databases	1430:1487	existing available genome-wide association study databases	1430:1487	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	7	78	theme	lean	1215:1218	arg1	mass					1220:1223	lean mass	1215:1223	lean mass	1215:1223	Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R).
30721968	5	79	theme	genome-wide	499:509	arg1	analyses					523:530	genome-wide association analyses	499:530	genome-wide association analyses	499:530	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	1	80	theme	important	81:89	arg1	role					91:94	an important role	78:94	an important role	78:94	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	4	81	from	impact	374:379	arg1	architecture					426:437	genetic architecture	418:437	genetic architecture of LM	418:443	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	6	82	theme	single-nucleotide	914:930	arg1	SNPs					947:950	SNPs	947:950	SNPs	947:950	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	6	82	theme	single-nucleotide	914:930	arg1	polymorphisms					932:944	Seven single-nucleotide polymorphisms	908:944	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B),	900:1008	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	9	83	theme	LM	1490:1491	arg1	alleles					1504:1510	LM increasing alleles	1490:1510	LM increasing alleles of SNPs in sumo wrestler loci	1490:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	4	84	theme	different	384:392	arg1	adjustments					403:413	different fat mass adjustments	384:413	different fat mass adjustments	384:413	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	9	85	from	loci	1649:1652	arg1	alleles					1615:1621	LM increasing alleles	1601:1621	LM increasing alleles of SNPs in "body builder" loci	1601:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	10	86	theme	LM	1748:1749	arg1	TNRC6B					1758:1763	TNRC6B	1758:1763	TNRC6B	1758:1763	Conclusions In conclusion, we identified one novel LM locus (TNRC6B).
30721968	10	86	theme	LM	1748:1749	arg1	locus					1751:1755	one novel LM locus	1738:1755	one novel LM locus (TNRC6B)	1738:1764	Conclusions In conclusion, we identified one novel LM locus (TNRC6B).
30721968	11	87	theme	fat	1938:1940	arg1	mass					1942:1945	fat mass	1938:1945	fat mass	1938:1945	Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
30721968	9	88	theme	sumo	1523:1526	arg1	loci					1537:1540	sumo wrestler loci	1523:1540	sumo wrestler loci	1523:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	5	89	theme	fat	814:816	arg1	mass					818:821	fat mass	814:821	fat mass as a percentage of body mass	814:850	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	9	90	theme	SNPs	1515:1518	arg1	alleles					1504:1510	LM increasing alleles	1490:1510	LM increasing alleles of SNPs in sumo wrestler loci	1490:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	4	91	theme	LM	469:470	arg1	loci					472:475	additional LM loci	458:475	additional LM loci	458:475	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	6	92	from	cohorts	1083:1089	arg1	individuals					1063:1073	an additional 47,227 individuals	1042:1073	an additional 47,227 individuals from 29 cohorts	1042:1089	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	1	93	theme	Lean	52:55	arg1	mass					62:65	Background Lean body mass	41:65	Background Lean body mass (LM)	41:70	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	1	93	theme	Lean	52:55	arg1	LM					68:69	LM	68:69	LM	68:69	Background Lean body mass (LM) plays an important role in mobility and metabolic function.
30721968	3	94	theme	lean	322:325	arg1	mass					327:330	lean mass	322:330	lean mass	322:330	Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.
30721968	6	95	dep	Results	900:906	arg1	SNPs					947:950	SNPs	947:950	SNPs	947:950	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	6	95	dep	Results	900:906	arg1	polymorphisms					932:944	Seven single-nucleotide polymorphisms	908:944	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B),	900:1008	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	5	96	theme	European	565:572	arg1	ancestry					574:581	European ancestry	565:581	European ancestry	565:581	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	11	97	from	increase	1817:1824	arg1	mass					1834:1837	lean mass	1829:1837	lean mass	1829:1837	Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
30721968	4	98	theme	LM	442:443	arg1	architecture					426:437	genetic architecture	418:437	genetic architecture of LM	418:443	Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
30721968	5	99	theme	fat	742:744	arg1	adjustments					751:761	fat mass adjustments	742:761	fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms)	742:897	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	100	theme	whole-body	536:545	arg1	LM					547:548	whole-body LM	536:548	whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry)	536:647	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	5	101	theme	body	842:845	arg1	mass					847:850	body mass	842:850	body mass	842:850	Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).
30721968	6	102	theme	separate	956:963	arg1	loci					965:968	separate loci	956:968	separate loci	956:968	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	6	102	theme	separate	956:963	arg1	locus					994:998	one novel LM locus	981:998	one novel LM locus (TNRC6B)	981:1007	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	11	103	theme	metabolic	1891:1899	arg1	traits					1901:1906	metabolic traits	1891:1906	metabolic traits	1891:1906	Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
30721968	0	104	theme	mass	35:38	arg1	genetics					18:25	the genetics	14:25	the genetics of lean mass	14:38	Disentangling the genetics of lean mass.
30721968	9	105	from	loci	1537:1540	arg1	alleles					1504:1510	LM increasing alleles	1490:1510	LM increasing alleles of SNPs in sumo wrestler loci	1490:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	9	106	theme	metabolic	1574:1582	arg1	profile					1584:1590	an adverse metabolic profile	1563:1590	an adverse metabolic profile	1563:1590	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	11	107	theme	determined	1806:1815	arg1	increase					1817:1824	a genetically determined increase	1792:1824	a genetically determined increase in lean mass	1792:1837	Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
30721968	9	108	from	SNPs	1515:1518	arg1	loci					1537:1540	sumo wrestler loci	1523:1540	sumo wrestler loci	1523:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	9	109	theme	LM	1601:1602	arg1	alleles					1615:1621	LM increasing alleles	1601:1621	LM increasing alleles of SNPs in "body builder" loci	1601:1652	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	6	110	theme	novel	985:989	arg1	TNRC6B					1001:1006	TNRC6B	1001:1006	TNRC6B	1001:1006	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	6	110	theme	novel	985:989	arg1	locus					994:998	one novel LM locus	981:998	one novel LM locus (TNRC6B)	981:1007	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	9	111	from	alleles	1504:1510	arg1	loci					1537:1540	sumo wrestler loci	1523:1540	sumo wrestler loci	1523:1540	Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.
30721968	6	112	theme	LM	991:992	arg1	TNRC6B					1001:1006	TNRC6B	1001:1006	TNRC6B	1001:1006	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
30721968	6	112	theme	LM	991:992	arg1	locus					994:998	one novel LM locus	981:998	one novel LM locus (TNRC6B)	981:1007	Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts.
31480247	6	0	theme	full-length	1278:1288	arg1	cardosin					1290:1297	the full-length cardosin	1274:1297	the full-length cardosin	1274:1297	This is also true when the PSI domain is analyzed in the context of the full-length cardosin.
31480247	7	1	theme	comprehensive	1386:1398	arg1	study					1400:1404	a more comprehensive study	1379:1404	a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole	1379:1479	Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.
31480247	7	2	dep	opening	1314:1320	arg1	gaps					1340:1343	exciting research gaps	1322:1343	opening exciting research gaps	1314:1343	Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.
31480247	5	3	dep	observed	972:979	arg1	Using					851:855	Using	851:855	Using site-directed mutagenesis to obtain mutated versions of the two PSIs	851:924	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	0	4	theme	Specific	90:97	arg1	Insert					99:104	the Plant Specific Insert	80:104	the Plant Specific Insert	80:104	N-Linked Glycosylation Modulates Golgi-Independent Vacuolar Sorting Mediated by the Plant Specific Insert.
31480247	5	5	theme	protein	1060:1066	arg1	trafficking					1041:1051	the trafficking	1037:1051	the trafficking of the protein	1037:1066	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	3	6	from	differences	691:701	arg1	terms					706:710	terms	706:710	terms of post-translational modifications	706:746	Given the high sequence similarity between the PSI domains, we sought to depict the differences in terms of post-translational modifications.
31480247	2	7	theme	related	532:538	arg1	PSIs					540:543	two related PSIs	528:543	two related PSIs	528:543	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	8	dep	cardosin	425:432	arg1	characteristic					487:500	a characteristic	485:500	a characteristic shared by all PSIs	485:519	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	8	dep	cardosin	425:432	arg1	ability					470:476	this Golgi-bypass ability	452:476	this Golgi-bypass ability	452:476	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	9	theme	ER-to-Golgi	585:595	arg1	blockage					597:604	ER-to-Golgi blockage	585:604	ER-to-Golgi blockage	585:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	10	theme	unconventional	265:278	arg1	sorting					280:286	unconventional sorting	265:286	unconventional sorting to the vacuole	265:301	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	1	11	theme	endoplasmic	174:184	arg1	reticulum					186:194	the endoplasmic reticulum	170:194	the endoplasmic reticulum	170:194	In plant cells, the conventional route to the vacuole involves the endoplasmic reticulum, the Golgi and the prevacuolar compartment.
31480247	2	12	theme	different	560:568	arg1	sensitivity					570:580	different sensitivity	560:580	different sensitivity to ER-to-Golgi blockage	560:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	13	theme	Golgi-bypass	457:468	arg1	characteristic					487:500	a characteristic	485:500	a characteristic shared by all PSIs	485:519	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	13	theme	Golgi-bypass	457:468	arg1	ability					470:476	this Golgi-bypass ability	452:476	this Golgi-bypass ability	452:476	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	4	14	gly	N-glycosylated	810:823	arg1	one					803:805	one	803:805	one	803:805	In fact, one feature that draws our attention is that one is N-glycosylated and the other one is not.
31480247	0	15	theme	N-Linked	0:7	arg1	Glycosylation					9:21	N-Linked Glycosylation	0:21	N-Linked Glycosylation	0:21	N-Linked Glycosylation Modulates Golgi-Independent Vacuolar Sorting Mediated by the Plant Specific Insert.
31480247	7	16	theme	exciting	1322:1329	arg1	gaps					1340:1343	exciting research gaps	1322:1343	opening exciting research gaps	1314:1343	Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.
31480247	0	17	theme	Golgi-Independent	33:49	arg1	Sorting					60:66	Golgi-Independent Vacuolar Sorting	33:66	Golgi-Independent Vacuolar Sorting Mediated by the Plant Specific Insert	33:104	N-Linked Glycosylation Modulates Golgi-Independent Vacuolar Sorting Mediated by the Plant Specific Insert.
31480247	1	18	theme	plant	110:114	arg1	cells					116:120	plant cells	110:120	plant cells	110:120	In plant cells, the conventional route to the vacuole involves the endoplasmic reticulum, the Golgi and the prevacuolar compartment.
31480247	5	19	gly	glycosylation	948:960	arg2	motif					962:966	the glycosylation motif	944:966	the glycosylation motif	944:966	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	5	20	theme	native	1110:1115	arg1	form					1130:1133	its native glycosylated form	1106:1133	its native glycosylated form	1106:1133	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	7	21	theme	research	1331:1338	arg1	gaps					1340:1343	exciting research gaps	1322:1343	opening exciting research gaps	1314:1343	Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.
31480247	7	22	theme	unconventional	1436:1449	arg1	sorting					1458:1464	this unconventional direct sorting	1431:1464	this unconventional direct sorting	1431:1464	Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.
31480247	5	23	theme	mutated	893:899	arg1	versions					901:908	mutated versions	893:908	mutated versions of the two PSIs	893:924	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	2	24	theme	Insert	385:390	arg1	case					358:361	the case	354:361	the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage	354:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	24	theme	Insert	385:390	arg1	which					345:349	which	345:349	which	345:349	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	5	25	theme	glycosylated	1117:1128	arg1	form					1130:1133	its native glycosylated form	1106:1133	its native glycosylated form	1106:1133	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	7	26	theme	direct	1451:1456	arg1	sorting					1458:1464	this unconventional direct sorting	1431:1464	this unconventional direct sorting	1431:1464	Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.
31480247	6	27	theme	PSI	1233:1235	arg1	domain					1237:1242	the PSI domain	1229:1242	the PSI domain	1229:1242	This is also true when the PSI domain is analyzed in the context of the full-length cardosin.
31480247	2	28	theme	Plant-Specific	370:383	arg1	PSI					393:395	PSI	393:395	PSI	393:395	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	28	theme	Plant-Specific	370:383	arg1	Insert					385:390	the Plant-Specific Insert	366:390	the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage	366:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	0	29	theme	Vacuolar	51:58	arg1	Sorting					60:66	Golgi-Independent Vacuolar Sorting	33:66	Golgi-Independent Vacuolar Sorting Mediated by the Plant Specific Insert	33:104	N-Linked Glycosylation Modulates Golgi-Independent Vacuolar Sorting Mediated by the Plant Specific Insert.
31480247	3	30	theme	post-translational	715:732	arg1	modifications					734:746	post-translational modifications	715:746	post-translational modifications	715:746	Given the high sequence similarity between the PSI domains, we sought to depict the differences in terms of post-translational modifications.
31480247	2	31	theme	cardosin	425:432	arg1	PSI					393:395	PSI	393:395	PSI	393:395	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	31	theme	cardosin	425:432	arg1	Insert					385:390	the Plant-Specific Insert	366:390	the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage	366:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	5	32	theme	glycosylation	999:1011	arg1	pattern					1013:1019	the glycosylation pattern	995:1019	the glycosylation pattern	995:1019	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	2	33	theme	proteinase	414:423	arg1	cardosin					425:432	the aspartic proteinase cardosin	401:432	the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage	401:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	33	theme	proteinase	414:423	arg1	A.					434:435	A.	434:435	A.	434:435	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	3	34	theme	modifications	734:746	arg1	terms					706:710	terms	706:710	terms of post-translational modifications	706:746	Given the high sequence similarity between the PSI domains, we sought to depict the differences in terms of post-translational modifications.
31480247	5	35	theme	glycosylation	948:960	arg1	motif					962:966	the glycosylation motif	944:966	the glycosylation motif	944:966	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	2	36	theme	aspartic	405:412	arg1	cardosin					425:432	the aspartic proteinase cardosin	401:432	the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage	401:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	36	theme	aspartic	405:412	arg1	A.					434:435	A.	434:435	A.	434:435	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	3	37	theme	sequence	622:629	arg1	similarity					631:640	the high sequence similarity	613:640	the high sequence similarity between the PSI domains	613:664	Given the high sequence similarity between the PSI domains, we sought to depict the differences in terms of post-translational modifications.
31480247	5	38	gly	glycosylated	1117:1128	arg1	form					1130:1133	its native glycosylated form	1106:1133	its native glycosylated form	1106:1133	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	7	39	theme	mechanisms	1413:1422	arg1	study					1400:1404	a more comprehensive study	1379:1404	a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole	1379:1479	Regardless of opening exciting research gaps, the results obtained so far need a more comprehensive study of the mechanisms behind this unconventional direct sorting to the vacuole.
31480247	5	40	theme	PSIs	921:924	arg1	versions					901:908	mutated versions	893:908	mutated versions of the two PSIs	893:924	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	1	41	theme	conventional	127:138	arg1	route					140:144	the conventional route	123:144	the conventional route to the vacuole	123:159	In plant cells, the conventional route to the vacuole involves the endoplasmic reticulum, the Golgi and the prevacuolar compartment.
31480247	1	42	theme	prevacuolar	215:225	arg1	compartment					227:237	the prevacuolar compartment	211:237	the prevacuolar compartment	211:237	In plant cells, the conventional route to the vacuole involves the endoplasmic reticulum, the Golgi and the prevacuolar compartment.
31480247	5	43	gly	non-glycosylated	1075:1090	arg1	PSI-B					1092:1096	the non-glycosylated PSI-B	1071:1096	the non-glycosylated PSI-B	1071:1096	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	5	43	gly	non-glycosylated	1075:1090	arg1	able					1139:1142	able	1139:1142	able	1139:1142	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	5	44	theme	site-directed	857:869	arg1	mutagenesis					871:881	site-directed mutagenesis	857:881	site-directed mutagenesis	857:881	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	0	45	theme	Plant	84:88	arg1	Insert					99:104	the Plant Specific Insert	80:104	the Plant Specific Insert	80:104	N-Linked Glycosylation Modulates Golgi-Independent Vacuolar Sorting Mediated by the Plant Specific Insert.
31480247	3	46	theme	high	617:620	arg1	similarity					631:640	the high sequence similarity	613:640	the high sequence similarity between the PSI domains	613:664	Given the high sequence similarity between the PSI domains, we sought to depict the differences in terms of post-translational modifications.
31480247	5	47	theme	ER-to-Golgi	1154:1164	arg1	blockage					1166:1173	ER-to-Golgi blockage	1154:1173	ER-to-Golgi blockage	1154:1173	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	6	48	theme	cardosin	1290:1297	arg1	context					1263:1269	the context	1259:1269	the context of the full-length cardosin	1259:1297	This is also true when the PSI domain is analyzed in the context of the full-length cardosin.
31480247	3	49	theme	PSI	654:656	arg1	domains					658:664	the PSI domains	650:664	the PSI domains	650:664	Given the high sequence similarity between the PSI domains, we sought to depict the differences in terms of post-translational modifications.
31480247	2	50	contain	have	555:558	arg2	sensitivity					570:580	different sensitivity	560:580	different sensitivity to ER-to-Golgi blockage	560:604	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	2	50	contain	have	555:558	arg1	PSIs					540:543	two related PSIs	528:543	two related PSIs	528:543	However, over the years, unconventional sorting to the vacuole, bypassing the Golgi, has been described, which is the case of the Plant-Specific Insert (PSI) of the aspartic proteinase cardosin A. Interestingly, this Golgi-bypass ability is not a characteristic shared by all PSIs, since two related PSIs showed to have different sensitivity to ER-to-Golgi blockage.
31480247	5	51	theme	non-glycosylated	1075:1090	arg1	PSI-B					1092:1096	the non-glycosylated PSI-B	1071:1096	the non-glycosylated PSI-B	1071:1096	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
31480247	5	51	theme	non-glycosylated	1075:1090	arg1	able					1139:1142	able	1139:1142	able	1139:1142	Using site-directed mutagenesis to obtain mutated versions of the two PSIs, with and without the glycosylation motif, we observed that altering the glycosylation pattern interferes with the trafficking of the protein as the non-glycosylated PSI-B, unlike its native glycosylated form, is able to bypass ER-to-Golgi blockage and accumulate in the vacuole.
29861440	3	0	theme	Multiple	374:381	arg1	studies					383:389	Multiple studies	374:389	Multiple studies	374:389	Multiple studies also showed that cell cycle might be modulated by O-GlcNAc.
29861440	4	1	theme	mitotic	536:542	arg1	organization					552:563	mitotic spindle organization	536:563	mitotic spindle organization	536:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	10	2	theme	cells	1340:1344	arg1	collection					1326:1335	collection	1326:1335	collection	1326:1335	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	2	theme	cells	1340:1344	arg1	selection					1312:1320	selection	1312:1320	selection	1312:1320	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	2	theme	cells	1340:1344	arg1	requirement					1413:1423	a challenging, but necessary requirement	1384:1423	a challenging, but necessary requirement for O-GlcNAc studies	1384:1444	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	9	3	theme	time	1300:1303	arg1	period					1290:1295	a short period	1282:1295	a short period of time	1282:1303	Our data verify that O-GlcNAc is elevated during mitosis, but also emphasize that O-GlcNAc levels can significantly change in a short period of time.
29861440	8	4	theme	round	1087:1091	arg1	cells					1100:1104	harvesting round shaped cells	1076:1104	harvesting round shaped cells from the G₂/M fraction of the synchronized cells	1076:1153	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	6	5	theme	G₂	844:845	arg1	phase					853:857	G₁, S, G₂ and M phase	837:857	phase	853:857	O-GlcNAc levels in G₁, S, G₂ and M phase were measured.
29861440	1	6	theme	threonine	179:187	arg1	modification					152:163	a dynamic post-translational modification	123:163	a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins	123:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	6	theme	threonine	179:187	arg1	N-acetylglucosamine					89:107	O-linked N-acetylglucosamine	80:107	O-linked N-acetylglucosamine (O-GlcNAc)	80:118	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	8	7	from	fraction	1120:1127	arg1	cells					1100:1104	harvesting round shaped cells	1076:1104	harvesting round shaped cells from the G₂/M fraction of the synchronized cells	1076:1153	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	1	8	link	O-linked	80:87	arg1	O-GlcNAc					110:117	O-GlcNAc	110:117	O-GlcNAc	110:117	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	8	link	O-linked	80:87	arg1	N-acetylglucosamine					89:107	O-linked N-acetylglucosamine	80:107	O-linked N-acetylglucosamine (O-GlcNAc)	80:118	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	8	link	O-linked	80:87	arg1	modification					152:163	a dynamic post-translational modification	123:163	a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins	123:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	10	9	theme	necessary	1403:1411	arg1	collection					1326:1335	collection	1326:1335	collection	1326:1335	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	9	theme	necessary	1403:1411	arg1	selection					1312:1320	selection	1312:1320	selection	1312:1320	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	9	theme	necessary	1403:1411	arg1	requirement					1413:1423	a challenging, but necessary requirement	1384:1423	a challenging, but necessary requirement for O-GlcNAc studies	1384:1444	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	10	theme	O-GlcNAc	1429:1436	arg1	studies					1438:1444	O-GlcNAc studies	1429:1444	O-GlcNAc studies	1429:1444	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	7	11	theme	other	971:975	arg1	phases					988:993	the other cell cycle phases	967:993	the other cell cycle phases	967:993	We observed that O-GlcNAc levels are significantly increased during mitosis in comparison to the other cell cycle phases.
29861440	4	12	from	role	464:467	arg1	phosphorylation					576:590	histone phosphorylation	568:590	histone phosphorylation	568:590	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	4	12	from	role	464:467	arg1	regulation					488:497	the regulation	484:497	the regulation of some cell cycle processes such as mitotic spindle organization	484:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	7	13	theme	O-GlcNAc	891:898	arg1	levels					900:905	O-GlcNAc levels	891:905	O-GlcNAc levels	891:905	We observed that O-GlcNAc levels are significantly increased during mitosis in comparison to the other cell cycle phases.
29861440	4	14	theme	regulation	647:656	arg1	behaviour					625:633	the general behaviour	613:633	the general behaviour of O-GlcNAc regulation during cell cycle	613:674	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	4	14	theme	regulation	647:656	arg1	controversial					685:697	controversial	685:697	controversial	685:697	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	5	15	theme	HeLa	777:780	arg1	cells					782:786	HeLa cells	777:786	HeLa cells	777:786	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	4	16	theme	processes	518:526	arg1	phosphorylation					576:590	histone phosphorylation	568:590	histone phosphorylation	568:590	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	4	16	theme	processes	518:526	arg1	regulation					488:497	the regulation	484:497	the regulation of some cell cycle processes such as mitotic spindle organization	484:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	8	17	theme	mitotic	1045:1051	arg1	cells					1053:1057	mitotic cells	1045:1057	mitotic cells	1045:1057	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	6	18	theme	S	841:841	arg1	phase					853:857	G₁, S, G₂ and M phase	837:857	phase	853:857	O-GlcNAc levels in G₁, S, G₂ and M phase were measured.
29861440	2	19	theme	signal	329:334	arg1	transduction					336:347	signal transduction	329:347	signal transduction	329:347	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	4	20	theme	O-GlcNAc	638:645	arg1	regulation					647:656	O-GlcNAc regulation	638:656	O-GlcNAc regulation	638:656	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	4	21	theme	cycle	512:516	arg1	organization					552:563	mitotic spindle organization	536:563	mitotic spindle organization	536:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	4	21	theme	cycle	512:516	arg1	processes					518:526	some cell cycle processes	502:526	some cell cycle processes such as mitotic spindle organization	502:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	7	22	theme	cell	977:980	arg1	phases					988:993	the other cell cycle phases	967:993	the other cell cycle phases	967:993	We observed that O-GlcNAc levels are significantly increased during mitosis in comparison to the other cell cycle phases.
29861440	1	23	theme	O-linked	80:87	arg1	O-GlcNAc					110:117	O-GlcNAc	110:117	O-GlcNAc	110:117	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	23	theme	O-linked	80:87	arg1	N-acetylglucosamine					89:107	O-linked N-acetylglucosamine	80:107	O-linked N-acetylglucosamine (O-GlcNAc)	80:118	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	23	theme	O-linked	80:87	arg1	modification					152:163	a dynamic post-translational modification	123:163	a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins	123:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	3	24	theme	cell	408:411	arg1	cycle					413:417	cell cycle	408:417	cell cycle	408:417	Multiple studies also showed that cell cycle might be modulated by O-GlcNAc.
29861440	6	25	theme	G₁	837:838	arg1	phase					853:857	G₁, S, G₂ and M phase	837:857	phase	853:857	O-GlcNAc levels in G₁, S, G₂ and M phase were measured.
29861440	9	26	theme	O-GlcNAc	1238:1245	arg1	levels					1247:1252	O-GlcNAc levels	1238:1252	O-GlcNAc levels	1238:1252	Our data verify that O-GlcNAc is elevated during mitosis, but also emphasize that O-GlcNAc levels can significantly change in a short period of time.
29861440	8	27	theme	cells	1149:1153	arg1	fraction					1120:1127	the G₂/M fraction	1111:1127	the G₂/M fraction of the synchronized cells	1111:1153	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	8	28	theme	harvesting	1076:1085	arg1	cells					1100:1104	harvesting round shaped cells	1076:1104	harvesting round shaped cells from the G₂/M fraction of the synchronized cells	1076:1153	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	1	29	from	modification	152:163	arg1	proteins					225:232	nuclear and cytoplasmic proteins	201:232	nuclear and cytoplasmic proteins	201:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	30	theme	nuclear	201:207	arg1	proteins					225:232	nuclear and cytoplasmic proteins	201:232	nuclear and cytoplasmic proteins	201:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	0	31	theme	O-Linked	0:7	arg1	N-Acetylglucosamine					9:27	O-Linked N-Acetylglucosamine	0:27	O-Linked N-Acetylglucosamine	0:27	O-Linked N-Acetylglucosamine Transiently Elevates in HeLa Cells during Mitosis.
29861440	4	32	theme	O-GlcNAc	472:479	arg1	role					464:467	the role	460:467	the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation	460:590	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	8	33	theme	shaped	1093:1098	arg1	cells					1100:1104	harvesting round shaped cells	1076:1104	harvesting round shaped cells from the G₂/M fraction of the synchronized cells	1076:1153	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	6	34	theme	O-GlcNAc	818:825	arg1	levels					827:832	O-GlcNAc levels	818:832	O-GlcNAc levels in G₁, S, G₂ and M phase	818:857	O-GlcNAc levels in G₁, S, G₂ and M phase were measured.
29861440	2	35	theme	protein	353:359	arg1	degradation					361:371	protein degradation	353:371	protein degradation	353:371	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	7	36	theme	cycle	982:986	arg1	phases					988:993	the other cell cycle phases	967:993	the other cell cycle phases	967:993	We observed that O-GlcNAc levels are significantly increased during mitosis in comparison to the other cell cycle phases.
29861440	1	37	theme	cytoplasmic	213:223	arg1	proteins					225:232	nuclear and cytoplasmic proteins	201:232	nuclear and cytoplasmic proteins	201:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	8	38	theme	synchronized	1136:1147	arg1	cells					1149:1153	the synchronized cells	1132:1153	the synchronized cells	1132:1153	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	4	39	theme	general	617:623	arg1	behaviour					625:633	the general behaviour	613:633	the general behaviour of O-GlcNAc regulation during cell cycle	613:674	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	4	39	theme	general	617:623	arg1	controversial					685:697	controversial	685:697	controversial	685:697	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	5	40	theme	overall	750:756	arg1	levels					767:772	overall O-GlcNAc levels	750:772	overall O-GlcNAc levels	750:772	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	10	41	theme	challenging	1386:1396	arg1	collection					1326:1335	collection	1326:1335	collection	1326:1335	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	41	theme	challenging	1386:1396	arg1	selection					1312:1320	selection	1312:1320	selection	1312:1320	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	41	theme	challenging	1386:1396	arg1	requirement					1413:1423	a challenging, but necessary requirement	1384:1423	a challenging, but necessary requirement for O-GlcNAc studies	1384:1444	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	1	42	dep	serine	168:173	arg1	residues					189:196	residues	189:196	residues	189:196	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	0	43	theme	HeLa	53:56	arg1	Cells					58:62	HeLa Cells	53:62	HeLa Cells	53:62	O-Linked N-Acetylglucosamine Transiently Elevates in HeLa Cells during Mitosis.
29861440	10	44	from	checkpoints	1369:1379	arg1	collection					1326:1335	collection	1326:1335	collection	1326:1335	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	44	from	checkpoints	1369:1379	arg1	selection					1312:1320	selection	1312:1320	selection	1312:1320	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	10	44	from	checkpoints	1369:1379	arg1	requirement					1413:1423	a challenging, but necessary requirement	1384:1423	a challenging, but necessary requirement for O-GlcNAc studies	1384:1444	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	5	45	theme	O-GlcNAc	758:765	arg1	levels					767:772	overall O-GlcNAc levels	750:772	overall O-GlcNAc levels	750:772	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	2	46	theme	cellular	273:280	arg1	metabolism					317:326	carbohydrate metabolism	304:326	carbohydrate metabolism	304:326	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	2	46	theme	cellular	273:280	arg1	transduction					336:347	signal transduction	329:347	signal transduction	329:347	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	2	46	theme	cellular	273:280	arg1	degradation					361:371	protein degradation	353:371	protein degradation	353:371	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	2	46	theme	cellular	273:280	arg1	mechanisms					282:291	many cellular mechanisms	268:291	many cellular mechanisms	268:291	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	5	47	theme	levels	767:772	arg1	changes					739:745	the dynamic changes	727:745	the dynamic changes of overall O-GlcNAc levels in HeLa cells	727:786	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	4	48	theme	cell	507:510	arg1	organization					552:563	mitotic spindle organization	536:563	mitotic spindle organization	536:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	4	48	theme	cell	507:510	arg1	processes					518:526	some cell cycle processes	502:526	some cell cycle processes such as mitotic spindle organization	502:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	2	49	theme	many	268:271	arg1	metabolism					317:326	carbohydrate metabolism	304:326	carbohydrate metabolism	304:326	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	2	49	theme	many	268:271	arg1	transduction					336:347	signal transduction	329:347	signal transduction	329:347	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	2	49	theme	many	268:271	arg1	degradation					361:371	protein degradation	353:371	protein degradation	353:371	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	2	49	theme	many	268:271	arg1	mechanisms					282:291	many cellular mechanisms	268:291	many cellular mechanisms	268:291	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	4	50	theme	histone	568:574	arg1	phosphorylation					576:590	histone phosphorylation	568:590	histone phosphorylation	568:590	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	8	51	theme	G₂/M	1115:1118	arg1	fraction					1120:1127	the G₂/M fraction	1111:1127	the G₂/M fraction of the synchronized cells	1111:1153	However, this change could only be detected when mitotic cells were enriched by harvesting round shaped cells from the G₂/M fraction of the synchronized cells.
29861440	2	52	theme	O-GlcNAc	235:242	arg1	modification					244:255	O-GlcNAc modification	235:255	O-GlcNAc modification	235:255	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	9	53	theme	short	1284:1288	arg1	period					1290:1295	a short period	1282:1295	a short period of time	1282:1303	Our data verify that O-GlcNAc is elevated during mitosis, but also emphasize that O-GlcNAc levels can significantly change in a short period of time.
29861440	1	54	theme	dynamic	125:131	arg1	modification					152:163	a dynamic post-translational modification	123:163	a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins	123:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	54	theme	dynamic	125:131	arg1	N-acetylglucosamine					89:107	O-linked N-acetylglucosamine	80:107	O-linked N-acetylglucosamine (O-GlcNAc)	80:118	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	5	55	theme	dynamic	731:737	arg1	changes					739:745	the dynamic changes	727:745	the dynamic changes of overall O-GlcNAc levels in HeLa cells	727:786	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	2	56	theme	carbohydrate	304:315	arg1	metabolism					317:326	carbohydrate metabolism	304:326	carbohydrate metabolism	304:326	O-GlcNAc modification influences many cellular mechanisms, including carbohydrate metabolism, signal transduction and protein degradation.
29861440	1	57	theme	post-translational	133:150	arg1	modification					152:163	a dynamic post-translational modification	123:163	a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins	123:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	57	theme	post-translational	133:150	arg1	N-acetylglucosamine					89:107	O-linked N-acetylglucosamine	80:107	O-linked N-acetylglucosamine (O-GlcNAc)	80:118	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	4	58	theme	cell	665:668	arg1	cycle					670:674	cell cycle	665:674	cell cycle	665:674	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	6	59	theme	M	851:851	arg1	phase					853:857	G₁, S, G₂ and M phase	837:857	phase	853:857	O-GlcNAc levels in G₁, S, G₂ and M phase were measured.
29861440	10	60	theme	cell-cycle	1358:1367	arg1	checkpoints					1369:1379	specific cell-cycle checkpoints	1349:1379	specific cell-cycle checkpoints	1349:1379	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	5	61	from	changes	739:745	arg1	cells					782:786	HeLa cells	777:786	HeLa cells	777:786	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	5	62	theme	double	794:799	arg1	block					811:815	double thymidine block	794:815	double thymidine block	794:815	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	10	63	theme	specific	1349:1356	arg1	checkpoints					1369:1379	specific cell-cycle checkpoints	1349:1379	specific cell-cycle checkpoints	1349:1379	Thus, selection and collection of cells at specific cell-cycle checkpoints is a challenging, but necessary requirement for O-GlcNAc studies.
29861440	6	64	from	levels	827:832	arg1	phase					853:857	G₁, S, G₂ and M phase	837:857	phase	853:857	O-GlcNAc levels in G₁, S, G₂ and M phase were measured.
29861440	5	65	theme	thymidine	801:809	arg1	block					811:815	double thymidine block	794:815	double thymidine block	794:815	In this study, we analysed the dynamic changes of overall O-GlcNAc levels in HeLa cells using double thymidine block.
29861440	4	66	theme	spindle	544:550	arg1	organization					552:563	mitotic spindle organization	536:563	mitotic spindle organization	536:563	Although the role of O-GlcNAc in the regulation of some cell cycle processes such as mitotic spindle organization or histone phosphorylation is well established, the general behaviour of O-GlcNAc regulation during cell cycle is still controversial.
29861440	1	67	theme	serine	168:173	arg1	modification					152:163	a dynamic post-translational modification	123:163	a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins	123:232	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
29861440	1	67	theme	serine	168:173	arg1	N-acetylglucosamine					89:107	O-linked N-acetylglucosamine	80:107	O-linked N-acetylglucosamine (O-GlcNAc)	80:118	O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins.
31105673	5	0	theme	same	875:878	arg1	concentration					880:892	the same concentration	871:892	the same concentration	871:892	For most of the strains tested of these bacteria the product was bactericidal as well as bacteriostatic at the same concentration, and the minimum bactericidal concentrations ranged from 16 to 256 μg/mL.
31105673	10	1	theme	cells	1918:1922	arg1	number					1897:1902	the number	1893:1902	the number of non-viable cells	1893:1922	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	1	2	theme	pharmaceutical	240:253	arg1	industry					255:262	the pharmaceutical industry	236:262	the pharmaceutical industry	236:262	The screening for alternatives to antibiotics is an urgent need for the pharmaceutical industry.
31105673	8	3	theme	mode	1490:1493	arg1	knowledge					1473:1481	the knowledge	1469:1481	the knowledge of the mode of action of the product	1469:1518	During the study, the techniques used were evaluated to clarify their contribution to the knowledge of the mode of action of the product.
31105673	10	4	theme	altered	1846:1852	arg1	permeability					1863:1874	altered membrane permeability	1846:1874	altered membrane permeability	1846:1874	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	11	5	theme	other	2282:2286	arg1	techniques					2288:2297	other techniques	2282:2297	other techniques	2282:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	5	6	theme	bactericidal	911:922	arg1	concentrations					924:937	the minimum bactericidal concentrations	899:937	the minimum bactericidal concentrations	899:937	For most of the strains tested of these bacteria the product was bactericidal as well as bacteriostatic at the same concentration, and the minimum bactericidal concentrations ranged from 16 to 256 μg/mL.
31105673	11	7	theme	mode	2199:2202	arg1	studies					2184:2190	studies	2184:2190	studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques	2184:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	9	8	theme	cells	1639:1643	arg1	viability					1622:1630	the viability	1618:1630	the viability of the cells	1618:1643	The survival test elucidated whether the modifications displayed using other techniques affected the viability of the cells or on the contrary, the cells remained viable even with evident changes in their structure, composition or morphology.
31105673	5	9	from	concentration	880:892	arg1	bactericidal					829:840	bactericidal	829:840	bactericidal	829:840	For most of the strains tested of these bacteria the product was bactericidal as well as bacteriostatic at the same concentration, and the minimum bactericidal concentrations ranged from 16 to 256 μg/mL.
31105673	5	9	from	concentration	880:892	arg1	product					817:823	the product	813:823	the product	813:823	For most of the strains tested of these bacteria the product was bactericidal as well as bacteriostatic at the same concentration, and the minimum bactericidal concentrations ranged from 16 to 256 μg/mL.
31105673	0	10	theme	Action	83:88	arg1	Mode					75:78	the Mode	71:78	the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens	71:165	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	8	11	theme	action	1498:1503	arg1	mode					1490:1493	the mode	1486:1493	the mode of action of the product	1486:1518	During the study, the techniques used were evaluated to clarify their contribution to the knowledge of the mode of action of the product.
31105673	3	12	theme	bactericidal	544:555	arg1	effect					557:562	its bacteriostatic and bactericidal effect	521:562	its bacteriostatic and bactericidal effect	521:562	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	2	13	theme	alternatives	278:289	arg1	alternatives					278:289	these alternatives	272:289	these alternatives	272:289	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	2	13	theme	alternatives	278:289	arg1	extracts					320:327	the citrus fruit extracts	303:327	the citrus fruit extracts	303:327	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	2	13	theme	alternatives	278:289	arg1	One					265:267	One	265:267	One	265:267	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	11	14	theme	antimicrobials	2217:2230	arg1	action					2207:2212	action	2207:2212	action of antimicrobials to make a correct interpretation of the data from other techniques	2207:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	3	15	dep	Salmonella	663:672	arg1	enterica					674:681	enterica	674:681	enterica	674:681	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	0	16	theme	Promising	95:103	arg1	Extract					133:139	a Promising Non-antibiotic Citrus Fruit Extract	93:139	a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens	93:165	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	5	17	dep	256	957:959	arg1	to					954:955	to	954:955	to	954:955	For most of the strains tested of these bacteria the product was bactericidal as well as bacteriostatic at the same concentration, and the minimum bactericidal concentrations ranged from 16 to 256 μg/mL.
31105673	6	18	dep	Fourier	1138:1144	arg1	transform					1146:1154	transform	1146:1154	transform infrared spectroscopy	1146:1176	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	3	19	from	pathogens	604:612	arg1	effect					557:562	its bacteriostatic and bactericidal effect	521:562	its bacteriostatic and bactericidal effect	521:562	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	19	from	pathogens	604:612	arg1	mode					572:575	its mode	568:575	its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp	568:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	2	20	theme	Gram-negative	393:405	arg1	bacteria					425:432	Gram-negative and Gram-positive bacteria	393:432	Gram-negative and Gram-positive bacteria	393:432	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	10	21	theme	cells	1987:1991	arg1	viability					1969:1977	the viability	1965:1977	the viability of some cells	1965:1991	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	11	22	from	techniques	2288:2297	arg1	data					2272:2275	the data	2268:2275	the data from other techniques	2268:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	11	22	from	techniques	2288:2297	arg1	interpretation					2250:2263	a correct interpretation	2240:2263	a correct interpretation of the data from other techniques	2240:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	3	23	dep	Escherichia	645:655	arg1	coli					657:660	coli	657:660	coli	657:660	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	23	dep	Escherichia	645:655	arg1	Salmonella					663:672	Salmonella	663:672	Salmonella	663:672	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	24	theme	bacteriostatic	525:538	arg1	effect					557:562	its bacteriostatic and bactericidal effect	521:562	its bacteriostatic and bactericidal effect	521:562	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	11	25	theme	action	2207:2212	arg1	mode					2199:2202	the mode	2195:2202	the mode of action of antimicrobials to make a correct interpretation of the data from other techniques	2195:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	3	26	theme	citrus	448:453	arg1	extracts					455:462	these citrus extracts	442:462	these citrus extracts	442:462	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	11	27	from	indispensable	2167:2179	arg1	studies					2184:2190	studies	2184:2190	studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques	2184:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	6	28	from	changes	1008:1014	arg1	structure					1037:1045	structure	1037:1045	structure	1037:1045	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	6	28	from	changes	1008:1014	arg1	permeability					1023:1034	permeability	1023:1034	permeability	1023:1034	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	6	28	from	changes	1008:1014	arg1	morphology					1064:1073	morphology	1064:1073	morphology	1064:1073	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	6	28	from	changes	1008:1014	arg1	composition					1048:1058	composition	1048:1058	composition	1048:1058	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	2	29	theme	citrus	307:312	arg1	alternatives					278:289	these alternatives	272:289	these alternatives	272:289	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	2	29	theme	citrus	307:312	arg1	extracts					320:327	the citrus fruit extracts	303:327	the citrus fruit extracts	303:327	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	2	29	theme	citrus	307:312	arg1	One					265:267	One	265:267	One	265:267	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	10	30	theme	non-viable	1907:1916	arg1	cells					1918:1922	non-viable cells	1907:1922	non-viable cells	1907:1922	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	0	31	theme	In	0:1	arg1	Susceptibility					9:22	In vitro Susceptibility	0:22	In vitro Susceptibility	0:22	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	11	32	theme	correct	2242:2248	arg1	interpretation					2250:2263	a correct interpretation	2240:2263	a correct interpretation of the data from other techniques	2240:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	2	33	theme	antibacterial	362:374	arg1	activity					376:383	a significant antibacterial activity	348:383	a significant antibacterial activity against Gram-negative and Gram-positive bacteria	348:432	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	6	34	theme	scanning	1182:1189	arg1	microscopy					1200:1209	scanning electron microscopy	1182:1209	scanning electron microscopy	1182:1209	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	0	35	theme	Citrus	120:125	arg1	Extract					133:139	a Promising Non-antibiotic Citrus Fruit Extract	93:139	a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens	93:165	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	5	36	theme	minimum	903:909	arg1	concentrations					924:937	the minimum bactericidal concentrations	899:937	the minimum bactericidal concentrations	899:937	For most of the strains tested of these bacteria the product was bactericidal as well as bacteriostatic at the same concentration, and the minimum bactericidal concentrations ranged from 16 to 256 μg/mL.
31105673	6	37	theme	flow	1122:1125	arg1	cytometry					1127:1135	flow cytometry	1122:1135	flow cytometry	1122:1135	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	3	38	from	action	580:585	arg1	pathogens					604:612	the important pathogens	590:612	the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp	590:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	6	39	dep	transform	1146:1154	arg1	infrared					1156:1163	infrared	1156:1163	transform infrared spectroscopy	1146:1176	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	6	40	theme	bacterial	1082:1090	arg1	envelope					1092:1099	the bacterial envelope	1078:1099	the bacterial envelope	1078:1099	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	0	41	theme	Non-antibiotic	105:118	arg1	Extract					133:139	a Promising Non-antibiotic Citrus Fruit Extract	93:139	a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens	93:165	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	11	42	theme	survival	2130:2137	arg1	test					2139:2142	the survival test	2126:2142	the survival test	2126:2142	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	11	43	theme	apparent	2074:2081	arg1	damage					2083:2088	no apparent damage	2071:2088	no apparent damage	2071:2088	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	3	44	dep	pathogens	604:612	arg1	jejuni					637:642	jejuni	637:642	jejuni	637:642	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	44	dep	pathogens	604:612	arg1	Campylobacter					614:626	Campylobacter	614:626	Campylobacter	614:626	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	44	dep	pathogens	604:612	arg1	ssp					683:685	Escherichia coli, Salmonella enterica ssp	645:685	Escherichia coli, Salmonella enterica ssp	645:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	11	45	with	microscopy	2055:2064	arg1	damage					2083:2088	no apparent damage	2071:2088	no apparent damage	2071:2088	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	0	46	theme	Extract	133:139	arg1	Action					83:88	Action	83:88	Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens	83:165	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	2	47	theme	Gram-positive	411:423	arg1	bacteria					425:432	Gram-negative and Gram-positive bacteria	393:432	Gram-negative and Gram-positive bacteria	393:432	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	7	48	theme	specific	1365:1372	arg1	effects					1374:1380	other specific effects	1359:1380	other specific effects	1359:1380	The main effect of the product was found over carbohydrates and polysaccharides, inducing the release of microvesicles by the cells in addition to other specific effects.
31105673	3	49	theme	extracts	455:462	arg1	One					435:437	One	435:437	One	435:437	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	49	theme	extracts	455:462	arg1	extracts					455:462	these citrus extracts	442:462	these citrus extracts	442:462	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	7	50	theme	microvesicles	1317:1329	arg1	release					1306:1312	the release	1302:1312	the release of microvesicles by the cells	1302:1342	The main effect of the product was found over carbohydrates and polysaccharides, inducing the release of microvesicles by the cells in addition to other specific effects.
31105673	7	51	theme	product	1235:1241	arg1	effect					1221:1226	The main effect	1212:1226	The main effect of the product	1212:1241	The main effect of the product was found over carbohydrates and polysaccharides, inducing the release of microvesicles by the cells in addition to other specific effects.
31105673	0	52	theme	Fruit	127:131	arg1	Extract					133:139	a Promising Non-antibiotic Citrus Fruit Extract	93:139	a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens	93:165	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	11	53	from	interpretation	2250:2263	arg1	techniques					2288:2297	other techniques	2282:2297	other techniques	2282:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	7	54	theme	other	1359:1363	arg1	effects					1374:1380	other specific effects	1359:1380	other specific effects	1359:1380	The main effect of the product was found over carbohydrates and polysaccharides, inducing the release of microvesicles by the cells in addition to other specific effects.
31105673	11	55	theme	electron	2046:2053	arg1	microscopy					2055:2064	scanning electron microscopy	2037:2064	scanning electron microscopy with no apparent damage	2037:2088	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	0	56	theme	Several	149:155	arg1	Pathogens					157:165	Several Pathogens	149:165	Several Pathogens	149:165	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	8	57	theme	product	1512:1518	arg1	action					1498:1503	action	1498:1503	action of the product	1498:1518	During the study, the techniques used were evaluated to clarify their contribution to the knowledge of the mode of action of the product.
31105673	3	58	dep	Campylobacter	614:626	arg1	coli					628:631	Campylobacter coli	614:631	Campylobacter coli	614:631	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	4	59	theme	Clostridium	698:708	arg1	difficile					710:718	Clostridium difficile	698:718	Clostridium difficile	698:718	enterica, Clostridium difficile, C. perfringens, and Staphylococcus aureus.
31105673	0	60	theme	Techniques	42:51	arg1	Susceptibility					9:22	In vitro Susceptibility	0:22	In vitro Susceptibility	0:22	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	0	60	theme	Techniques	42:51	arg1	Evaluation					28:37	Evaluation	28:37	Evaluation	28:37	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	11	61	theme	scanning	2037:2044	arg1	microscopy					2055:2064	scanning electron microscopy	2037:2064	scanning electron microscopy with no apparent damage	2037:2088	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	10	62	theme	cells	1826:1830	arg1	proportion					1812:1821	the proportion	1808:1821	the proportion of cells detected with altered membrane permeability	1808:1874	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	10	62	theme	cells	1826:1830	arg1	higher					1881:1886	higher	1881:1886	higher	1881:1886	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	3	63	theme	action	580:585	arg1	effect					557:562	its bacteriostatic and bactericidal effect	521:562	its bacteriostatic and bactericidal effect	521:562	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	63	theme	action	580:585	arg1	mode					572:575	its mode	568:575	its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp	568:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	64	from	effect	557:562	arg1	pathogens					604:612	the important pathogens	590:612	the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp	590:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	10	65	theme	Flow	1764:1767	arg1	cytometry					1769:1777	Flow cytometry	1764:1777	Flow cytometry	1764:1777	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	9	66	theme	evident	1701:1707	arg1	changes					1709:1715	evident changes	1701:1715	evident changes in their structure, composition or morphology	1701:1761	The survival test elucidated whether the modifications displayed using other techniques affected the viability of the cells or on the contrary, the cells remained viable even with evident changes in their structure, composition or morphology.
31105673	10	67	theme	membrane	1854:1861	arg1	permeability					1863:1874	altered membrane permeability	1846:1874	altered membrane permeability	1846:1874	Flow cytometry showed that for some strains the proportion of cells detected with altered membrane permeability were higher than the number of non-viable cells, and therefore the damage did not affect the viability of some cells.
31105673	6	68	theme	envelope	1092:1099	arg1	structure					1037:1045	structure	1037:1045	structure	1037:1045	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	6	68	theme	envelope	1092:1099	arg1	permeability					1023:1034	permeability	1023:1034	permeability	1023:1034	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	6	68	theme	envelope	1092:1099	arg1	morphology					1064:1073	morphology	1064:1073	morphology	1064:1073	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	6	68	theme	envelope	1092:1099	arg1	composition					1048:1058	composition	1048:1058	composition	1048:1058	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	11	69	theme	data	2272:2275	arg1	interpretation					2250:2263	a correct interpretation	2240:2263	a correct interpretation of the data from other techniques	2240:2297	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	1	70	theme	urgent	220:225	arg1	need					227:230	an urgent need	217:230	an urgent need for the pharmaceutical industry	217:262	The screening for alternatives to antibiotics is an urgent need for the pharmaceutical industry.
31105673	1	70	theme	urgent	220:225	arg1	screening					172:180	The screening	168:180	The screening for alternatives to antibiotics	168:212	The screening for alternatives to antibiotics is an urgent need for the pharmaceutical industry.
31105673	9	71	theme	survival	1525:1532	arg1	test					1534:1537	The survival test	1521:1537	The survival test	1521:1537	The survival test elucidated whether the modifications displayed using other techniques affected the viability of the cells or on the contrary, the cells remained viable even with evident changes in their structure, composition or morphology.
31105673	3	72	theme	Escherichia	645:655	arg1	Campylobacter					614:626	Campylobacter	614:626	Campylobacter	614:626	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	3	72	theme	Escherichia	645:655	arg1	ssp					683:685	Escherichia coli, Salmonella enterica ssp	645:685	Escherichia coli, Salmonella enterica ssp	645:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	6	73	theme	electron	1191:1198	arg1	microscopy					1200:1209	scanning electron microscopy	1182:1209	scanning electron microscopy	1182:1209	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	2	74	theme	fruit	314:318	arg1	alternatives					278:289	these alternatives	272:289	these alternatives	272:289	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	2	74	theme	fruit	314:318	arg1	extracts					320:327	the citrus fruit extracts	303:327	the citrus fruit extracts	303:327	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	2	74	theme	fruit	314:318	arg1	One					265:267	One	265:267	One	265:267	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	9	75	from	changes	1709:1715	arg1	structure					1726:1734	their structure	1720:1734	their structure	1720:1734	The survival test elucidated whether the modifications displayed using other techniques affected the viability of the cells or on the contrary, the cells remained viable even with evident changes in their structure, composition or morphology.
31105673	9	75	from	changes	1709:1715	arg1	morphology					1752:1761	morphology	1752:1761	morphology	1752:1761	The survival test elucidated whether the modifications displayed using other techniques affected the viability of the cells or on the contrary, the cells remained viable even with evident changes in their structure, composition or morphology.
31105673	9	75	from	changes	1709:1715	arg1	composition					1737:1747	composition	1737:1747	composition	1737:1747	The survival test elucidated whether the modifications displayed using other techniques affected the viability of the cells or on the contrary, the cells remained viable even with evident changes in their structure, composition or morphology.
31105673	7	76	theme	main	1216:1219	arg1	effect					1221:1226	The main effect	1212:1226	The main effect of the product	1212:1241	The main effect of the product was found over carbohydrates and polysaccharides, inducing the release of microvesicles by the cells in addition to other specific effects.
31105673	11	77	from	studies	2184:2190	arg1	indispensable					2167:2179	indispensable	2167:2179	indispensable	2167:2179	On the contrary, some cells observed using scanning electron microscopy with no apparent damage, were demonstrated non-viable using the survival test, making this technique indispensable in studies of the mode of action of antimicrobials to make a correct interpretation of the data from other techniques.
31105673	3	78	theme	important	594:602	arg1	pathogens					604:612	the important pathogens	590:612	the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp	590:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	2	79	theme	significant	350:360	arg1	activity					376:383	a significant antibacterial activity	348:383	a significant antibacterial activity against Gram-negative and Gram-positive bacteria	348:432	One of these alternatives seems to be the citrus fruit extracts, which are showing a significant antibacterial activity against Gram-negative and Gram-positive bacteria.
31105673	3	80	from	mode	572:575	arg1	pathogens					604:612	the important pathogens	590:612	the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp	590:685	One of these citrus extracts, named BIOCITRO®, is assessed in this study to elucidate its bacteriostatic and bactericidal effect and its mode of action on the important pathogens Campylobacter coli, C. jejuni, Escherichia coli, Salmonella enterica ssp.
31105673	6	81	theme	action	990:995	arg1	mode					982:985	the mode	978:985	the mode of action	978:995	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	0	82	dep	In	0:1	arg1	vitro					3:7	vitro	3:7	vitro	3:7	In vitro Susceptibility and Evaluation of Techniques for Understanding the Mode of Action of a Promising Non-antibiotic Citrus Fruit Extract Against Several Pathogens.
31105673	6	83	theme	important	998:1006	arg1	changes					1008:1014	important changes	998:1014	important changes in the permeability, structure, composition and morphology of the bacterial envelope	998:1099	Regarding the mode of action, important changes in the permeability, structure, composition and morphology of the bacterial envelope were evidenced using flow cytometry, Fourier transform infrared spectroscopy and scanning electron microscopy.
31105673	9	84	theme	other	1592:1596	arg1	techniques					1598:1607	other techniques	1592:1607	other techniques	1592:1607	The survival test elucidated whether the modifications displayed using other techniques affected the viability of the cells or on the contrary, the cells remained viable even with evident changes in their structure, composition or morphology.
30089930	2	0	theme	Astragalus	591:600	arg1	fermentation					602:613	Astragalus fermentation	591:613	Astragalus fermentation	591:613	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	4	1	from	%	931:931	arg1	day					947:949	day 10	947:952	day 10	947:952	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	3	2	from	3081.99 mg/kg	835:847	arg1	day					775:777	day 15	775:780	day 15	775:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	2	from	3081.99 mg/kg	835:847	arg1	day					823:825	day 15	823:828	day 15	823:828	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	2	from	3081.99 mg/kg	835:847	arg1	day					799:801	day 30	799:804	day 30	799:804	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	2	from	3081.99 mg/kg	835:847	arg1	day					852:854	day 20	852:857	day 20	852:857	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	0	3	theme	sequencing	190:199	arg1	molecule					170:177	single molecule	163:177	single molecule	163:177	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	0	3	theme	sequencing	190:199	arg1	technology					201:210	real-time sequencing technology	180:210	real-time sequencing technology	180:210	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	1	4	theme	health-promoting	301:316	arg1	compounds					329:337	health-promoting biological compounds	301:337	health-promoting biological compounds	301:337	We investigated if fermentation with probiotic cultures could improve the production of health-promoting biological compounds in Astragalus membranaceus.
30089930	0	5	theme	plantarum	88:96	arg1	properties					34:43	physicochemical properties	18:43	physicochemical properties	18:43	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	0	5	theme	plantarum	88:96	arg1	composition					59:69	bacterial composition	49:69	bacterial composition	49:69	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	1	6	theme	biological	318:327	arg1	compounds					329:337	health-promoting biological compounds	301:337	health-promoting biological compounds	301:337	We investigated if fermentation with probiotic cultures could improve the production of health-promoting biological compounds in Astragalus membranaceus.
30089930	0	7	theme	faecium-fermented	115:131	arg1	membranaceus					144:155	Enterococcus faecium-fermented Astragalus membranaceus	102:155	Enterococcus faecium-fermented Astragalus membranaceus	102:155	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	6	8	theme	solid	1412:1416	arg1	process					1437:1443	the Astragalus solid state fermentation process	1397:1443	the Astragalus solid state fermentation process	1397:1443	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	1	9	theme	compounds	329:337	arg1	production					287:296	the production	283:296	the production of health-promoting biological compounds in Astragalus membranaceus	283:364	We investigated if fermentation with probiotic cultures could improve the production of health-promoting biological compounds in Astragalus membranaceus.
30089930	0	10	theme	Enterococcus	102:113	arg1	membranaceus					144:155	Enterococcus faecium-fermented Astragalus membranaceus	102:155	Enterococcus faecium-fermented Astragalus membranaceus	102:155	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	4	11	from	%	924:924	arg1	day					947:949	day 10	947:952	day 10	947:952	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	3	12	theme	acetic	654:659	arg1	acid					661:664	acetic acid	654:664	acetic acid	654:664	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	6	13	theme	E.	1321:1322	arg1	plantarum					1337:1345	E. faecium + L. plantarum	1321:1345	E. faecium + L. plantarum	1321:1345	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	0	14	theme	membranaceus	144:155	arg1	properties					34:43	physicochemical properties	18:43	physicochemical properties	18:43	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	0	14	theme	membranaceus	144:155	arg1	composition					59:69	bacterial composition	49:69	bacterial composition	49:69	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	2	15	theme	real-time	525:533	arg1	SMRT					558:561	SMRT	558:561	SMRT	558:561	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	15	theme	real-time	525:533	arg1	technology					546:555	real-time sequencing technology	525:555	real-time sequencing technology (SMRT)	525:562	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	15	theme	real-time	525:533	arg1	molecule					515:522	PacBio single molecule	501:522	PacBio single molecule	501:522	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	3	16	theme	production	634:643	arg1	rates					645:649	the production rates	630:649	the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum	630:751	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	16	theme	production	634:643	arg1	1866.24 mg/kg					758:770	1866.24 mg/kg	758:770	1866.24 mg/kg on day 15	758:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	2	17	theme	single	508:513	arg1	technology					546:555	real-time sequencing technology	525:555	real-time sequencing technology (SMRT)	525:562	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	17	theme	single	508:513	arg1	molecule					515:522	PacBio single molecule	501:522	PacBio single molecule	501:522	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	0	18	theme	Astragalus	133:142	arg1	membranaceus					144:155	Enterococcus faecium-fermented Astragalus membranaceus	102:155	Enterococcus faecium-fermented Astragalus membranaceus	102:155	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	4	19	from	21.6630 mg/g	979:990	arg1	day					1012:1014	day 15	1012:1017	day 15	1012:1017	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	2	20	theme	PacBio	501:506	arg1	technology					546:555	real-time sequencing technology	525:555	real-time sequencing technology (SMRT)	525:562	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	20	theme	PacBio	501:506	arg1	molecule					515:522	PacBio single molecule	501:522	PacBio single molecule	501:522	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	4	21	from	polysaccharides	903:917	arg1	day					1081:1083	day 20	1081:1086	day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively	1081:1161	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	6	22	theme	single	1379:1384	arg1	strains					1386:1392	single strains	1379:1392	single strains in the Astragalus solid state fermentation process	1379:1443	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	3	23	theme	methylacetic	667:678	arg1	acid					680:683	methylacetic acid	667:683	methylacetic acid	667:683	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	0	24	theme	real-time	180:188	arg1	molecule					170:177	single molecule	163:177	single molecule	163:177	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	0	24	theme	real-time	180:188	arg1	technology					201:210	real-time sequencing technology	180:210	real-time sequencing technology	180:210	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	6	25	theme	fermentation	1424:1435	arg1	process					1437:1443	the Astragalus solid state fermentation process	1397:1443	the Astragalus solid state fermentation process	1397:1443	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	1	26	theme	Astragalus	342:351	arg1	membranaceus					353:364	Astragalus membranaceus	342:364	Astragalus membranaceus	342:364	We investigated if fermentation with probiotic cultures could improve the production of health-promoting biological compounds in Astragalus membranaceus.
30089930	7	27	theme	sequencing	1482:1491	arg1	applicable					1505:1514	applicable	1505:1514	applicable	1505:1514	Our data demonstrated that the SMRT sequencing platform is applicable to quality assessment of Astragalus fermentation.
30089930	7	27	theme	sequencing	1482:1491	arg1	platform					1493:1500	the SMRT sequencing platform	1473:1500	the SMRT sequencing platform	1473:1500	Our data demonstrated that the SMRT sequencing platform is applicable to quality assessment of Astragalus fermentation.
30089930	3	28	theme	acid	680:683	arg1	rates					645:649	the production rates	630:649	the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum	630:751	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	28	theme	acid	680:683	arg1	1866.24 mg/kg					758:770	1866.24 mg/kg	758:770	1866.24 mg/kg on day 15	758:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	6	29	from	strains	1386:1392	arg1	process					1437:1443	the Astragalus solid state fermentation process	1397:1443	the Astragalus solid state fermentation process	1397:1443	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	0	30	theme	physicochemical	18:32	arg1	properties					34:43	physicochemical properties	18:43	physicochemical properties	18:43	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	0	31	theme	single	163:168	arg1	molecule					170:177	single molecule	163:177	single molecule	163:177	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	0	31	theme	single	163:168	arg1	technology					201:210	real-time sequencing technology	180:210	real-time sequencing technology	180:210	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	3	32	theme	aethyl	686:691	arg1	acid					700:703	aethyl acetic acid	686:703	aethyl acetic acid	686:703	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	33	theme	acid	661:664	arg1	rates					645:649	the production rates	630:649	the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum	630:751	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	33	theme	acid	661:664	arg1	1866.24 mg/kg					758:770	1866.24 mg/kg	758:770	1866.24 mg/kg on day 15	758:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	2	34	theme	sequencing	535:544	arg1	SMRT					558:561	SMRT	558:561	SMRT	558:561	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	34	theme	sequencing	535:544	arg1	technology					546:555	real-time sequencing technology	525:555	real-time sequencing technology (SMRT)	525:562	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	34	theme	sequencing	535:544	arg1	molecule					515:522	PacBio single molecule	501:522	PacBio single molecule	501:522	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	4	35	dep	polysaccharides	903:917	arg1	saponins					955:962	saponins	955:962	saponins	955:962	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	1	36	theme	probiotic	250:258	arg1	cultures					260:267	probiotic cultures	250:267	probiotic cultures	250:267	We investigated if fermentation with probiotic cultures could improve the production of health-promoting biological compounds in Astragalus membranaceus.
30089930	6	37	theme	Astragalus	1401:1410	arg1	process					1437:1443	the Astragalus solid state fermentation process	1397:1443	the Astragalus solid state fermentation process	1397:1443	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	4	38	from	19.6912 mg/g	965:976	arg1	day					1012:1014	day 15	1012:1017	day 15	1012:1017	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	7	39	theme	Astragalus	1541:1550	arg1	fermentation					1552:1563	Astragalus fermentation	1541:1563	Astragalus fermentation	1541:1563	Our data demonstrated that the SMRT sequencing platform is applicable to quality assessment of Astragalus fermentation.
30089930	3	40	theme	acetic	693:698	arg1	acid					700:703	aethyl acetic acid	686:703	aethyl acetic acid	686:703	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	0	41	theme	properties	34:43	arg1	Assessment					0:9	Assessment	0:9	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus	0:155	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	4	42	from	flavonoids	1024:1033	arg1	day					1081:1083	day 20	1081:1086	day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively	1081:1161	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	3	43	from	203.80 mg/kg	783:794	arg1	day					852:854	day 20	852:857	day 20	852:857	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	43	from	203.80 mg/kg	783:794	arg1	day					823:825	day 15	823:828	day 15	823:828	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	43	from	203.80 mg/kg	783:794	arg1	day					799:801	day 30	799:804	day 30	799:804	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	43	from	203.80 mg/kg	783:794	arg1	day					775:777	day 15	775:780	day 15	775:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	7	44	theme	quality	1519:1525	arg1	assessment					1527:1536	quality assessment	1519:1536	quality assessment of Astragalus fermentation	1519:1563	Our data demonstrated that the SMRT sequencing platform is applicable to quality assessment of Astragalus fermentation.
30089930	3	45	theme	acid	700:703	arg1	rates					645:649	the production rates	630:649	the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum	630:751	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	45	theme	acid	700:703	arg1	1866.24 mg/kg					758:770	1866.24 mg/kg	758:770	1866.24 mg/kg on day 15	758:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	6	46	theme	faecium + L.	1324:1335	arg1	plantarum					1337:1345	E. faecium + L. plantarum	1321:1345	E. faecium + L. plantarum	1321:1345	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	0	47	theme	composition	59:69	arg1	Assessment					0:9	Assessment	0:9	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus	0:155	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	1	48	from	production	287:296	arg1	membranaceus					353:364	Astragalus membranaceus	342:364	Astragalus membranaceus	342:364	We investigated if fermentation with probiotic cultures could improve the production of health-promoting biological compounds in Astragalus membranaceus.
30089930	4	49	dep	L.	1106:1107	arg1	plantarum					1109:1117	L. plantarum	1106:1117	L. plantarum	1106:1117	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	7	50	theme	fermentation	1552:1563	arg1	assessment					1527:1536	quality assessment	1519:1536	quality assessment of Astragalus fermentation	1519:1563	Our data demonstrated that the SMRT sequencing platform is applicable to quality assessment of Astragalus fermentation.
30089930	0	51	theme	bacterial	49:57	arg1	composition					59:69	bacterial composition	49:69	bacterial composition	49:69	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	1	52	with	fermentation	232:243	arg1	cultures					260:267	probiotic cultures	250:267	probiotic cultures	250:267	We investigated if fermentation with probiotic cultures could improve the production of health-promoting biological compounds in Astragalus membranaceus.
30089930	0	53	dep	properties	34:43	arg1	the					14:16	the	14:16	the	14:16	Assessment of the physicochemical properties and bacterial composition of Lactobacillus plantarum and Enterococcus faecium-fermented Astragalus membranaceus using single molecule, real-time sequencing technology.
30089930	4	54	from	%	942:942	arg1	day					947:949	day 10	947:952	day 10	947:952	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	3	55	theme	acid	716:719	arg1	rates					645:649	the production rates	630:649	the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum	630:751	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	55	theme	acid	716:719	arg1	1866.24 mg/kg					758:770	1866.24 mg/kg	758:770	1866.24 mg/kg on day 15	758:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	4	56	theme	production	880:889	arg1	rates					891:895	Other production rates	874:895	Other production rates	874:895	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	6	57	theme	positive	1357:1364	arg1	effects					1366:1372	more positive effects	1352:1372	more positive effects	1352:1372	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	5	58	used	used	1173:1176	arg2	SMRT					1164:1167	SMRT	1164:1167	SMRT	1164:1167	SMRT was used to analyze microbial composition, and we found that E. faecium and L. plantarum were the most prevalent species after fermentation for 3 days.
30089930	5	59	theme	microbial	1189:1197	arg1	composition					1199:1209	microbial composition	1189:1209	microbial composition	1189:1209	SMRT was used to analyze microbial composition, and we found that E. faecium and L. plantarum were the most prevalent species after fermentation for 3 days.
30089930	2	60	dep	probiotics	381:390	arg1	faecium					405:411	Enterococcus faecium	392:411	Enterococcus faecium	392:411	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	60	dep	probiotics	381:390	arg1	plantarum					428:436	Lactobacillus plantarum	414:436	Lactobacillus plantarum	414:436	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	2	60	dep	probiotics	381:390	arg1	plantarum					479:487	Enterococcus faecium + Lactobacillus plantarum	442:487	Enterococcus faecium + Lactobacillus plantarum	442:487	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	3	61	dep	faecium + L.	730:741	arg1	plantarum					743:751	E. faecium + L. plantarum	727:751	E. faecium + L. plantarum	727:751	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	62	from	1866.24 mg/kg	758:770	arg1	day					852:854	day 20	852:857	day 20	852:857	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	62	from	1866.24 mg/kg	758:770	arg1	day					823:825	day 15	823:828	day 15	823:828	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	62	from	1866.24 mg/kg	758:770	arg1	day					799:801	day 30	799:804	day 30	799:804	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	62	from	1866.24 mg/kg	758:770	arg1	day					775:777	day 15	775:780	day 15	775:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	6	63	theme	state	1418:1422	arg1	process					1437:1443	the Astragalus solid state fermentation process	1397:1443	the Astragalus solid state fermentation process	1397:1443	E. faecium + L. plantarum gave more positive effects than single strains in the Astragalus solid state fermentation process.
30089930	4	64	theme	Other	874:878	arg1	rates					891:895	Other production rates	874:895	Other production rates	874:895	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	4	65	dep	faecium + L.	1126:1137	arg1	plantarum					1139:1147	E. faecium + L. plantarum	1123:1147	E. faecium + L. plantarum	1123:1147	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	5	66	theme	prevalent	1272:1280	arg1	species					1282:1288	the most prevalent species	1263:1288	the most prevalent species	1263:1288	SMRT was used to analyze microbial composition, and we found that E. faecium and L. plantarum were the most prevalent species after fermentation for 3 days.
30089930	5	66	theme	prevalent	1272:1280	arg1	plantarum					1248:1256	L. plantarum	1245:1256	L. plantarum	1245:1256	SMRT was used to analyze microbial composition, and we found that E. faecium and L. plantarum were the most prevalent species after fermentation for 3 days.
30089930	5	66	theme	prevalent	1272:1280	arg1	faecium					1233:1239	E. faecium	1230:1239	E. faecium	1230:1239	SMRT was used to analyze microbial composition, and we found that E. faecium and L. plantarum were the most prevalent species after fermentation for 3 days.
30089930	4	67	from	20.2084 mg/g	996:1007	arg1	day					1012:1014	day 15	1012:1017	day 15	1012:1017	Other production rates were: polysaccharides, 9.43%, 8.51%, and 7.59% on day 10; saponins, 19.6912 mg/g, 21.6630 mg/g and 20.2084 mg/g on day 15; and flavonoids, 1.9032 mg/g, 2.0835 mg/g, and 1.7086 mg/g on day 20 using E. faecium, L. plantarum and E. faecium + L. plantarum, respectively.
30089930	2	68	theme	fermentation	602:613	arg1	quality					580:586	the quality	576:586	the quality of Astragalus fermentation	576:613	We tested the probiotics Enterococcus faecium, Lactobacillus plantarum and Enterococcus faecium + Lactobacillus plantarum and applied PacBio single molecule, real-time sequencing technology (SMRT) to evaluate the quality of Astragalus fermentation.
30089930	7	69	theme	SMRT	1477:1480	arg1	applicable					1505:1514	applicable	1505:1514	applicable	1505:1514	Our data demonstrated that the SMRT sequencing platform is applicable to quality assessment of Astragalus fermentation.
30089930	7	69	theme	SMRT	1477:1480	arg1	platform					1493:1500	the SMRT sequencing platform	1473:1500	the SMRT sequencing platform	1473:1500	Our data demonstrated that the SMRT sequencing platform is applicable to quality assessment of Astragalus fermentation.
30089930	3	70	theme	lactic	709:714	arg1	acid					716:719	lactic acid	709:719	lactic acid	709:719	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	71	from	996.04 mg/kg	807:818	arg1	day					852:854	day 20	852:857	day 20	852:857	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	71	from	996.04 mg/kg	807:818	arg1	day					823:825	day 15	823:828	day 15	823:828	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	71	from	996.04 mg/kg	807:818	arg1	day					799:801	day 30	799:804	day 30	799:804	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
30089930	3	71	from	996.04 mg/kg	807:818	arg1	day					775:777	day 15	775:780	day 15	775:780	We found that the production rates of acetic acid, methylacetic acid, aethyl acetic acid and lactic acid using E. faecium + L. plantarum were 1866.24 mg/kg on day 15, 203.80 mg/kg on day 30, 996.04 mg/kg on day 15, and 3081.99 mg/kg on day 20, respectively.
29507058	11	0	theme	gut	1757:1759	arg1	microbiome					1761:1770	gut microbiome	1757:1770	gut microbiome	1757:1770	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	5	1	from	patients	910:917	arg1	plasma					745:750	plasma	745:750	plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	745:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	4	2	with	patients	674:681	arg1	BP					693:694	high BP	688:694	high BP	688:694	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	4	3	theme	high	688:691	arg1	BP					693:694	high BP	688:694	high BP	688:694	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	9	4	theme	barrier	1543:1549	arg1	function					1551:1558	gut barrier function	1539:1558	gut barrier function	1539:1558	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	9	5	theme	mouse	1429:1433	arg1	model					1435:1439	The mouse model	1425:1439	The mouse model of HTN, chronic angiotensin II (Ang II) infusion,	1425:1489	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	4	6	theme	altered	638:644	arg1	production					655:664	altered butyrate production	638:664	altered butyrate production between patients with high BP and reference subjects	638:717	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	5	7	theme	augmented	833:841	arg1	helper					876:881	augmented gut-targetting proinflammatory T helper 17	833:884	augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	833:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	7	theme	augmented	833:841	arg1	Th17					887:890	Th17	887:890	Th17	887:890	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	9	8	theme	cardiovascular	1567:1580	arg1	system					1582:1587	the cardiovascular system	1563:1587	the cardiovascular system	1563:1587	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	4	9	theme	taxonomic	594:602	arg1	changes					619:625	taxonomic and functional changes	594:625	taxonomic and functional changes	594:625	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	10	10	theme	barrier	1650:1656	arg1	dysfunction					1658:1668	intestinal barrier dysfunction	1639:1668	intestinal barrier dysfunction	1639:1668	These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans.
29507058	5	11	theme	lipopolysaccharide	803:820	arg1	plasma					745:750	plasma	745:750	plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	745:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	4	12	theme	functional	608:617	arg1	changes					619:625	taxonomic and functional changes	594:625	taxonomic and functional changes	594:625	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	8	13	theme	regression	1243:1252	arg1	analysis					1254:1261	stepwise linear regression analysis	1227:1261	stepwise linear regression analysis of microbiome data	1227:1280	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	4	14	with	subjects	710:717	arg1	BP					693:694	high BP	688:694	high BP	688:694	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	5	15	from	plasma	745:750	arg1	patients					910:917	high BP patients	902:917	high BP patients	902:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	11	16	theme	diagnostic	1831:1840	arg1	avenues					1842:1848	the new therapeutic and diagnostic avenues	1807:1848	the new therapeutic and diagnostic avenues for HTN	1807:1856	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	11	16	theme	diagnostic	1831:1840	arg1	manipulation					1741:1752	manipulation	1741:1752	manipulation of gut microbiome and its barrier functions	1741:1796	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	4	17	theme	butyrate	646:653	arg1	production					655:664	altered butyrate production	638:664	altered butyrate production between patients with high BP and reference subjects	638:717	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	5	18	from	increases	732:740	arg1	plasma					745:750	plasma	745:750	plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	745:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	10	19	theme	intestinal	1639:1648	arg1	dysfunction					1658:1668	intestinal barrier dysfunction	1639:1668	intestinal barrier dysfunction	1639:1668	These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans.
29507058	8	20	theme	data	1277:1280	arg1	analysis					1254:1261	stepwise linear regression analysis	1227:1261	stepwise linear regression analysis of microbiome data	1227:1280	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	8	20	theme	data	1277:1280	arg1	markers					1298:1304	circulating markers	1286:1304	circulating markers of gut health	1286:1318	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	8	21	from	plasma	1393:1398	arg1	prediction					1359:1368	prediction	1359:1368	prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001)	1359:1422	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	5	22	theme	proinflammatory	858:872	arg1	helper					876:881	augmented gut-targetting proinflammatory T helper 17	833:884	augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	833:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	22	theme	proinflammatory	858:872	arg1	Th17					887:890	Th17	887:890	Th17	887:890	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	8	23	theme	circulating	1286:1296	arg1	markers					1298:1304	circulating markers	1286:1304	circulating markers of gut health	1286:1318	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	8	24	from	zonulin	1382:1388	arg1	SBP					1373:1375	SBP	1373:1375	SBP from zonulin in plasma (R2 = 0.4608, P<0.0001)	1373:1422	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	8	24	from	zonulin	1382:1388	arg1	prediction					1359:1368	prediction	1359:1368	prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001)	1359:1422	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	5	25	theme	helper	876:881	arg1	cells					893:897	augmented gut-targetting proinflammatory T helper 17 (Th17) cells	833:897	augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	833:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	3	26	dep	hypotheses	346:355	arg1	have					396:399	have	396:399	have distinct gut microbiomes	396:424	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	3	26	dep	hypotheses	346:355	arg1	predict					508:514	predict	508:514	could predict systolic BP (SBP)	502:532	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	0	27	dep	dysfunction	62:72	arg1	intestinal					32:41	intestinal	32:41	intestinal	32:41	Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.
29507058	0	28	theme	high	91:94	arg1	pressure					102:109	high blood pressure	91:109	high blood pressure	91:109	Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.
29507058	9	29	theme	chronic	1449:1455	arg1	infusion					1481:1488	chronic angiotensin II (Ang II) infusion	1449:1488	chronic angiotensin II (Ang II) infusion	1449:1488	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	9	29	theme	chronic	1449:1455	arg1	HTN					1444:1446	HTN	1444:1446	HTN	1444:1446	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	3	30	theme	present	315:321	arg1	study					323:327	the present study	311:327	the present study	311:327	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	11	31	theme	therapeutic	1815:1825	arg1	avenues					1842:1848	the new therapeutic and diagnostic avenues	1807:1848	the new therapeutic and diagnostic avenues for HTN	1807:1856	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	11	31	theme	therapeutic	1815:1825	arg1	manipulation					1741:1752	manipulation	1741:1752	manipulation of gut microbiome and its barrier functions	1741:1796	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	8	32	theme	health	1313:1318	arg1	analysis					1254:1261	stepwise linear regression analysis	1227:1261	stepwise linear regression analysis of microbiome data	1227:1280	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	8	32	theme	health	1313:1318	arg1	markers					1298:1304	circulating markers	1286:1304	circulating markers of gut health	1286:1318	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	11	33	theme	functions	1788:1796	arg1	avenues					1842:1848	the new therapeutic and diagnostic avenues	1807:1848	the new therapeutic and diagnostic avenues for HTN	1807:1856	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	11	33	theme	functions	1788:1796	arg1	manipulation					1741:1752	manipulation	1741:1752	manipulation of gut microbiome and its barrier functions	1741:1796	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	5	34	theme	Significant	720:730	arg1	increases					732:740	Significant increases	720:740	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	720:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	35	from	protein	785:791	arg1	patients					910:917	high BP patients	902:917	high BP patients	902:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	3	36	dep	function	458:465	arg1	markers					467:473	markers	467:473	markers	467:473	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	11	37	theme	new	1811:1813	arg1	avenues					1842:1848	the new therapeutic and diagnostic avenues	1807:1848	the new therapeutic and diagnostic avenues for HTN	1807:1856	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	11	37	theme	new	1811:1813	arg1	manipulation					1741:1752	manipulation	1741:1752	manipulation of gut microbiome and its barrier functions	1741:1796	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	0	38	theme	gut	13:15	arg1	Imbalance					0:8	Imbalance	0:8	Imbalance of gut	0:15	Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.
29507058	5	39	theme	BP	907:908	arg1	patients					910:917	high BP patients	902:917	high BP patients	902:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	6	40	theme	junction	1016:1023	arg1	Zonulin					984:990	Zonulin	984:990	Zonulin	984:990	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	6	40	theme	junction	1016:1023	arg1	regulator					1033:1041	a gut epithelial tight junction protein regulator	993:1041	a gut epithelial tight junction protein regulator	993:1041	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	3	41	theme	pressure	373:380	arg1	patients					387:394	high blood pressure (BP) patients	362:394	high blood pressure (BP) patients	362:394	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	8	42	theme	separate	1340:1347	arg1	cohort					1349:1354	a separate cohort	1338:1354	a separate cohort	1338:1354	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	3	43	theme	distinct	401:408	arg1	microbiomes					414:424	distinct gut microbiomes	401:424	distinct gut microbiomes	401:424	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	5	44	theme	fatty	766:770	arg1	I-FABP					794:799	I-FABP	794:799	I-FABP	794:799	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	44	theme	fatty	766:770	arg1	protein					785:791	intestinal fatty acid binding protein	755:791	intestinal fatty acid binding protein (I-FABP)	755:800	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	6	45	theme	epithelial	999:1008	arg1	Zonulin					984:990	Zonulin	984:990	Zonulin	984:990	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	6	45	theme	epithelial	999:1008	arg1	regulator					1033:1041	a gut epithelial tight junction protein regulator	993:1041	a gut epithelial tight junction protein regulator	993:1041	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	3	46	theme	high	362:365	arg1	BP					383:384	BP	383:384	BP	383:384	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	3	46	theme	high	362:365	arg1	pressure					373:380	high blood pressure	362:380	high blood pressure (BP) patients	362:394	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	3	47	theme	barrier	450:456	arg1	function					458:465	gut-epithelial barrier function markers and microbiome composition	435:500	function	458:465	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	0	48	theme	epithelial	43:52	arg1	dysfunction					62:72	and intestinal epithelial barrier dysfunction	28:72	dysfunction	62:72	Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.
29507058	7	49	dep	=	1163:1163	arg1	0.5301					1165:1170	0.5301	1165:1170	0.5301	1165:1170	Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001).
29507058	6	50	from	dysfunction	1098:1108	arg1	BP					1118:1119	high BP	1113:1119	high BP	1113:1119	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	1	51	theme	animal	209:214	arg1	models					216:221	animal models	209:221	animal models	209:221	Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models.
29507058	9	52	used	used	1495:1498	arg2	model					1435:1439	The mouse model	1425:1439	The mouse model of HTN, chronic angiotensin II (Ang II) infusion,	1425:1489	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	6	53	theme	gut	1086:1088	arg1	dysfunction					1098:1108	gut barrier dysfunction	1086:1108	gut barrier dysfunction in high BP	1086:1119	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	3	54	theme	microbiome	479:488	arg1	composition					490:500	microbiome composition	479:500	microbiome composition	479:500	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	0	55	theme	barrier	54:60	arg1	dysfunction					62:72	and intestinal epithelial barrier dysfunction	28:72	dysfunction	62:72	Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.
29507058	9	56	theme	butyrate	1526:1533	arg1	effects					1515:1521	the effects	1511:1521	the effects of butyrate and gut barrier function on the cardiovascular system and BP	1511:1594	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	4	57	theme	Fecal	535:539	arg1	samples					541:547	Fecal samples	535:547	Fecal samples	535:547	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	0	58	with	patients	77:84	arg1	pressure					102:109	high blood pressure	91:109	high blood pressure	91:109	Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.
29507058	3	59	theme	systolic	516:523	arg1	SBP					529:531	SBP	529:531	SBP	529:531	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	3	59	theme	systolic	516:523	arg1	BP					525:526	systolic BP	516:526	systolic BP (SBP)	516:532	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	9	60	theme	gut	1539:1541	arg1	function					1551:1558	gut barrier function	1539:1558	gut barrier function	1539:1558	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	5	61	theme	T	874:874	arg1	helper					876:881	augmented gut-targetting proinflammatory T helper 17	833:884	augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	833:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	61	theme	T	874:874	arg1	Th17					887:890	Th17	887:890	Th17	887:890	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	62	theme	binding	777:783	arg1	I-FABP					794:799	I-FABP	794:799	I-FABP	794:799	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	62	theme	binding	777:783	arg1	protein					785:791	intestinal fatty acid binding protein	755:791	intestinal fatty acid binding protein (I-FABP)	755:800	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	9	63	theme	function	1551:1558	arg1	effects					1515:1521	the effects	1511:1521	the effects of butyrate and gut barrier function on the cardiovascular system and BP	1511:1594	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	10	64	theme	microbiome	1674:1683	arg1	function					1685:1692	microbiome function	1674:1692	microbiome function	1674:1692	These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans.
29507058	8	65	from	SBP	1373:1375	arg1	plasma					1393:1398	plasma	1393:1398	plasma (R2 = 0.4608, P<0.0001)	1393:1422	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	6	66	theme	high	1113:1116	arg1	BP					1118:1119	high BP	1113:1119	high BP	1113:1119	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	9	67	theme	HTN	1444:1446	arg1	model					1435:1439	The mouse model	1425:1439	The mouse model of HTN, chronic angiotensin II (Ang II) infusion,	1425:1489	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	10	68	attach	linked	1698:1703	arg2	function					1685:1692	microbiome function	1674:1692	microbiome function	1674:1692	These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans.
29507058	10	68	attach	linked	1698:1703	arg2	dysfunction					1658:1668	intestinal barrier dysfunction	1639:1668	intestinal barrier dysfunction	1639:1668	These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans.
29507058	10	68	attach	linked	1698:1703	arg1	HTN					1708:1710	HTN	1708:1710	HTN in humans	1708:1720	These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans.
29507058	8	69	from	prediction	1359:1368	arg1	plasma					1393:1398	plasma	1393:1398	plasma (R2 = 0.4608, P<0.0001)	1393:1422	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	8	69	from	prediction	1359:1368	arg1	zonulin					1382:1388	zonulin	1382:1388	zonulin	1382:1388	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	7	70	theme	=	1163:1163	arg1	R2					1160:1161	R2	1160:1161	R2 = 0.5301	1160:1170	Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001).
29507058	1	71	theme	Recent	112:117	arg1	evidence					119:126	Recent evidence	112:126	Recent evidence	112:126	Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models.
29507058	8	72	theme	linear	1236:1241	arg1	analysis					1254:1261	stepwise linear regression analysis	1227:1261	stepwise linear regression analysis of microbiome data	1227:1280	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	3	73	from	objectives	297:306	arg1	study					323:327	the present study	311:327	the present study	311:327	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	5	74	from	lipopolysaccharide	803:820	arg1	patients					910:917	high BP patients	902:917	high BP patients	902:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	6	75	theme	gut	995:997	arg1	Zonulin					984:990	Zonulin	984:990	Zonulin	984:990	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	6	75	theme	gut	995:997	arg1	regulator					1033:1041	a gut epithelial tight junction protein regulator	993:1041	a gut epithelial tight junction protein regulator	993:1041	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	3	76	contain	have	396:399	arg1	patients					387:394	high blood pressure (BP) patients	362:394	high blood pressure (BP) patients	362:394	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	3	76	contain	have	396:399	arg2	microbiomes					414:424	distinct gut microbiomes	401:424	distinct gut microbiomes	401:424	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	1	77	from	hypertension	187:198	arg1	models					216:221	animal models	209:221	animal models	209:221	Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models.
29507058	5	78	theme	gut-targetting	843:856	arg1	helper					876:881	augmented gut-targetting proinflammatory T helper 17	833:884	augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	833:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	78	theme	gut-targetting	843:856	arg1	Th17					887:890	Th17	887:890	Th17	887:890	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	8	79	theme	microbiome	1266:1275	arg1	data					1277:1280	microbiome data	1266:1280	microbiome data	1266:1280	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	1	80	theme	gut	153:155	arg1	pathology					157:165	gut pathology	153:165	gut pathology	153:165	Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models.
29507058	7	81	dep	correlated	1139:1148	arg1	R2					1160:1161	R2	1160:1161	R2 = 0.5301	1160:1170	Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001).
29507058	0	82	theme	blood	96:100	arg1	pressure					102:109	high blood pressure	91:109	high blood pressure	91:109	Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.
29507058	1	83	with	link	140:143	arg1	HTN					201:203	HTN	201:203	HTN	201:203	Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models.
29507058	1	83	with	link	140:143	arg1	hypertension					187:198	hypertension	187:198	hypertension (HTN) in animal models	187:221	Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models.
29507058	5	84	theme	increased	932:940	arg1	inflammation					953:964	increased intestinal inflammation	932:964	increased intestinal inflammation	932:964	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	9	85	from	effects	1515:1521	arg1	BP					1593:1594	BP	1593:1594	BP	1593:1594	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	9	85	from	effects	1515:1521	arg1	system					1582:1587	the cardiovascular system	1563:1587	the cardiovascular system	1563:1587	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	8	86	theme	gut	1309:1311	arg1	health					1313:1318	gut health	1309:1318	gut health	1309:1318	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	5	87	theme	protein	785:791	arg1	plasma					745:750	plasma	745:750	plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	745:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	88	theme	cells	893:897	arg1	plasma					745:750	plasma	745:750	plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients	745:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	4	89	theme	reference	700:708	arg1	subjects					710:717	reference subjects	700:717	reference subjects	700:717	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	11	90	theme	barrier	1780:1786	arg1	functions					1788:1796	its barrier functions	1776:1796	its barrier functions	1776:1796	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	5	91	theme	high	902:905	arg1	patients					910:917	high BP patients	902:917	high BP patients	902:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	10	92	from	HTN	1708:1710	arg1	humans					1715:1720	humans	1715:1720	humans	1715:1720	These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans.
29507058	6	93	theme	protein	1025:1031	arg1	Zonulin					984:990	Zonulin	984:990	Zonulin	984:990	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	6	93	theme	protein	1025:1031	arg1	regulator					1033:1041	a gut epithelial tight junction protein regulator	993:1041	a gut epithelial tight junction protein regulator	993:1041	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	9	94	theme	angiotensin	1457:1467	arg1	infusion					1481:1488	chronic angiotensin II (Ang II) infusion	1449:1488	chronic angiotensin II (Ang II) infusion	1449:1488	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	9	94	theme	angiotensin	1457:1467	arg1	HTN					1444:1446	HTN	1444:1446	HTN	1444:1446	The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP.
29507058	11	95	theme	microbiome	1761:1770	arg1	avenues					1842:1848	the new therapeutic and diagnostic avenues	1807:1848	the new therapeutic and diagnostic avenues for HTN	1807:1856	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	11	95	theme	microbiome	1761:1770	arg1	manipulation					1741:1752	manipulation	1741:1752	manipulation of gut microbiome and its barrier functions	1741:1796	They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
29507058	5	96	theme	intestinal	755:764	arg1	I-FABP					794:799	I-FABP	794:799	I-FABP	794:799	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	96	theme	intestinal	755:764	arg1	protein					785:791	intestinal fatty acid binding protein	755:791	intestinal fatty acid binding protein (I-FABP)	755:800	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	8	97	theme	stepwise	1227:1234	arg1	analysis					1254:1261	stepwise linear regression analysis	1227:1261	stepwise linear regression analysis of microbiome data	1227:1280	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	6	98	theme	tight	1010:1014	arg1	Zonulin					984:990	Zonulin	984:990	Zonulin	984:990	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	6	98	theme	tight	1010:1014	arg1	regulator					1033:1041	a gut epithelial tight junction protein regulator	993:1041	a gut epithelial tight junction protein regulator	993:1041	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	3	99	theme	gut	410:412	arg1	microbiomes					414:424	distinct gut microbiomes	401:424	distinct gut microbiomes	401:424	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	5	100	theme	acid	772:775	arg1	I-FABP					794:799	I-FABP	794:799	I-FABP	794:799	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	5	100	theme	acid	772:775	arg1	protein					785:791	intestinal fatty acid binding protein	755:791	intestinal fatty acid binding protein (I-FABP)	755:800	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	8	101	dep	plasma	1393:1398	arg1	P<0.0001					1414:1421	P<0.0001	1414:1421	P<0.0001	1414:1421	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	8	101	dep	plasma	1393:1398	arg1	R2					1401:1402	R2	1401:1402	R2 = 0.4608	1401:1411	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
29507058	3	102	theme	blood	367:371	arg1	BP					383:384	BP	383:384	BP	383:384	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	3	102	theme	blood	367:371	arg1	pressure					373:380	high blood pressure	362:380	high blood pressure (BP) patients	362:394	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	7	103	dep	R2	1160:1161	arg1	P<0.0001					1173:1180	P<0.0001	1173:1180	P<0.0001	1173:1180	Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001).
29507058	6	104	theme	barrier	1090:1096	arg1	dysfunction					1098:1108	gut barrier dysfunction	1086:1108	gut barrier dysfunction in high BP	1086:1119	Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP.
29507058	4	105	theme	shotgun	562:568	arg1	metagenomics					570:581	shotgun metagenomics	562:581	shotgun metagenomics	562:581	Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects.
29507058	5	106	theme	intestinal	942:951	arg1	inflammation					953:964	increased intestinal inflammation	932:964	increased intestinal inflammation	932:964	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	3	107	theme	gut-epithelial	435:448	arg1	function					458:465	gut-epithelial barrier function markers and microbiome composition	435:500	function	458:465	Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP).
29507058	5	108	from	cells	893:897	arg1	patients					910:917	high BP patients	902:917	high BP patients	902:917	Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability.
29507058	8	109	theme	SBP	1373:1375	arg1	prediction					1359:1368	prediction	1359:1368	prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001)	1359:1422	Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001).
31775336	7	0	theme	ethanolic	1642:1650	arg1	extract					1652:1658	96% ethanolic extract	1638:1658	96% ethanolic extract	1638:1658	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	7	0	theme	ethanolic	1642:1650	arg1	active					1675:1680	active	1675:1680	active	1675:1680	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	8	1	theme	G.	1796:1797	arg1	herb					1807:1810	G. aparine herb	1796:1810	G. aparine herb	1796:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	0	2	theme	spread	156:161	arg1	Activity					53:60	In Vitro Immunomodulatory Activity	27:60	In Vitro Immunomodulatory Activity	27:60	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	2	theme	spread	156:161	arg1	species					163:169	a widely spread species	147:169	a widely spread species in the Galium genus	147:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	2	theme	spread	156:161	arg1	Profiles					14:21	Phytochemical Profiles	0:21	Phytochemical Profiles	0:21	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	2	3	theme	chemical	296:303	arg1	composition					305:315	chemical composition	296:315	chemical composition	296:315	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	7	4	theme	96	1638:1639	arg1	%					1640:1640	%	1640:1640	%	1640:1640	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	1	5	theme	folk	226:229	arg1	remedies					231:238	folk remedies	226:238	folk remedies	226:238	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	4	6	theme	immunomodulatory	848:863	arg1	activity					865:872	the immunomodulatory activity	844:872	the immunomodulatory activity of extracts	844:884	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	0	7	theme	Galium	178:183	arg1	genus					185:189	the Galium genus	174:189	the Galium genus	174:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	7	8	theme	blood	1620:1624	arg1	cells					1626:1630	immunocompetent blood cells	1604:1630	immunocompetent blood cells	1604:1630	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	5	9	theme	caffeic	1256:1262	arg1	derivatives					1269:1279	caffeic acid derivatives	1256:1279	caffeic acid derivatives	1256:1279	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	4	10	theme	qualitative	650:660	arg1	composition					662:672	The qualitative composition	646:672	The qualitative composition	646:672	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	4	11	theme	transformation	937:950	arg1	reaction					908:915	the reaction	904:915	the reaction of lymphocyte blast transformation	904:950	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	7	12	theme	herb	1537:1540	arg1	extracts					1552:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	5	13	theme	acid	1111:1114	arg1	derivatives					1116:1126	hydroxycinnamic acid derivatives	1095:1126	hydroxycinnamic acid derivatives	1095:1126	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	3	14	theme	acid	496:499	arg1	derivatives					501:511	hydroxycinnamic acid derivatives	480:511	hydroxycinnamic acid derivatives	480:511	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols were determined spectrophotometrically, with extractives and polysaccharides quantified gravimetrically.
31775336	7	15	theme	G.	1526:1527	arg1	extracts					1552:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	5	16	dep	monotropein	1004:1014	arg1	i.e.					998:1001	i.e.	998:1001	i.e.	998:1001	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	0	17	theme	family	126:131	arg1	L.					122:123	L.	122:123	L.	122:123	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	17	theme	family	126:131	arg1	Rubiaceae					133:141	family Rubiaceae	126:141	family Rubiaceae	126:141	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	5	18	theme	p-hydroxybenzoic	1072:1087	arg1	acid					1089:1092	p-hydroxybenzoic acid	1072:1092	p-hydroxybenzoic acid	1072:1092	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	4	19	theme	lymphocyte	920:929	arg1	transformation					937:950	lymphocyte blast transformation	920:950	lymphocyte blast transformation	920:950	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	2	20	with	maceration	423:432	arg1	ethanol					455:461	20%, 60% or 96% ethanol	439:461	20%, 60% or 96% ethanol	439:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	2	21	theme	%	446:446	arg1	ethanol					455:461	20%, 60% or 96% ethanol	439:461	20%, 60% or 96% ethanol	439:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	0	22	theme	Ethanolic	65:73	arg1	Extracts					75:82	Ethanolic Extracts	65:82	Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae,	65:142	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	2	23	dep	composition	305:315	arg1	the					292:294	the	292:294	the	292:294	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	0	24	from	Activity	53:60	arg1	L.					122:123	L.	122:123	L.	122:123	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	24	from	Activity	53:60	arg1	Rubiaceae					133:141	family Rubiaceae	126:141	family Rubiaceae	126:141	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	2	25	theme	aparine	355:361	arg1	extracts					378:385	G. aparine herb ethanolic extracts	352:385	G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol	352:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	0	26	theme	Phytochemical	0:12	arg1	Activity					53:60	In Vitro Immunomodulatory Activity	27:60	In Vitro Immunomodulatory Activity	27:60	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	26	theme	Phytochemical	0:12	arg1	Profiles					14:21	Phytochemical Profiles	0:21	Phytochemical Profiles	0:21	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	26	theme	Phytochemical	0:12	arg1	species					163:169	a widely spread species	147:169	a widely spread species in the Galium genus	147:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	1	27	theme	remedies	231:238	arg1	part					218:221	part	218:221	part of folk remedies and dietary supplements	218:262	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	1	27	theme	remedies	231:238	arg1	herb					196:199	The herb	192:199	The herb of G. aparine	192:213	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	1	28	theme	dietary	244:250	arg1	supplements					252:262	dietary supplements	244:262	dietary supplements	244:262	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	8	29	theme	further	1713:1719	arg1	research					1721:1728	further research	1713:1728	further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb	1713:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	2	30	theme	ethanolic	368:376	arg1	extracts					378:385	G. aparine herb ethanolic extracts	352:385	G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol	352:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	5	31	theme	asperulosidic	1052:1064	arg1	acid					1066:1069	asperulosidic acid	1052:1069	asperulosidic acid	1052:1069	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	5	32	dep	5-O-caffeoylquinic	1155:1172	arg1	3,4-O-dicaffeoylquinic					1175:1196	3,4-O-dicaffeoylquinic	1175:1196	3,4-O-dicaffeoylquinic	1175:1196	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	5	32	dep	5-O-caffeoylquinic	1155:1172	arg1	3,5-O-dicaffeoylquinic					1199:1220	3,5-O-dicaffeoylquinic	1199:1220	3,5-O-dicaffeoylquinic	1199:1220	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	8	33	theme	immunomodulatory	1753:1768	arg1	activity					1770:1777	immunomodulatory activity	1753:1777	immunomodulatory activity of extracts from G. aparine herb	1753:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	2	34	theme	immunomodulatory	321:336	arg1	activities					338:347	immunomodulatory activities	321:347	immunomodulatory activities	321:347	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	1	35	theme	G.	204:205	arg1	aparine					207:213	G. aparine	204:213	G. aparine	204:213	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	7	36	theme	%	1640:1640	arg1	extract					1652:1658	96% ethanolic extract	1638:1658	96% ethanolic extract	1638:1658	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	7	36	theme	%	1640:1640	arg1	active					1675:1680	active	1675:1680	active	1675:1680	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	0	37	from	L.	122:123	arg1	species					163:169	a widely spread species	147:169	a widely spread species in the Galium genus	147:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	37	from	L.	122:123	arg1	Activity					53:60	In Vitro Immunomodulatory Activity	27:60	In Vitro Immunomodulatory Activity	27:60	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	37	from	L.	122:123	arg1	Profiles					14:21	Phytochemical Profiles	0:21	Phytochemical Profiles	0:21	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	37	from	L.	122:123	arg1	Extracts					75:82	Ethanolic Extracts	65:82	Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae,	65:142	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	6	38	theme	quercetin	1405:1413	arg1	3-O-rhamnoglucoside-7-O-glucoside					1415:1447	quercetin 3-O-rhamnoglucoside-7-O-glucoside	1405:1447	quercetin 3-O-rhamnoglucoside-7-O-glucoside	1405:1447	Significantly, quercetin 3-O-rhamnoglucoside-7-O-glucoside was first isolated and identified in Galium species so far investigated.
31775336	4	39	theme	extracts	877:884	arg1	activity					865:872	the immunomodulatory activity	844:872	the immunomodulatory activity of extracts	844:884	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	7	40	theme	cells	1626:1630	arg1	activity					1592:1599	the transformational activity	1571:1599	the transformational activity of immunocompetent blood cells	1571:1630	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	8	41	theme	aparine	1799:1805	arg1	herb					1807:1810	G. aparine herb	1796:1810	G. aparine herb	1796:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	7	42	theme	immunocompetent	1604:1618	arg1	cells					1626:1630	immunocompetent blood cells	1604:1630	immunocompetent blood cells	1604:1630	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	7	43	theme	transformational	1575:1590	arg1	activity					1592:1599	the transformational activity	1571:1599	the transformational activity of immunocompetent blood cells	1571:1630	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	3	44	theme	derivatives	501:511	arg1	contents					468:475	The contents	464:475	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols	464:539	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols were determined spectrophotometrically, with extractives and polysaccharides quantified gravimetrically.
31775336	6	45	theme	Galium	1486:1491	arg1	species					1493:1499	Galium species	1486:1499	Galium species so far investigated	1486:1519	Significantly, quercetin 3-O-rhamnoglucoside-7-O-glucoside was first isolated and identified in Galium species so far investigated.
31775336	3	46	theme	hydroxycinnamic	480:494	arg1	derivatives					501:511	hydroxycinnamic acid derivatives	480:511	hydroxycinnamic acid derivatives	480:511	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols were determined spectrophotometrically, with extractives and polysaccharides quantified gravimetrically.
31775336	4	47	theme	blast	931:935	arg1	transformation					937:950	lymphocyte blast transformation	920:950	lymphocyte blast transformation	920:950	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	7	48	theme	ethanolic	1542:1550	arg1	extracts					1552:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	5	49	dep	acid	1043:1046	arg1	derivatives					1116:1126	hydroxycinnamic acid derivatives	1095:1126	hydroxycinnamic acid derivatives	1095:1126	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	5	49	dep	acid	1043:1046	arg1	flavonoids					1282:1291	flavonoids	1282:1291	flavonoids	1282:1291	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	5	49	dep	acid	1043:1046	arg1	acid					1089:1092	p-hydroxybenzoic acid	1072:1092	p-hydroxybenzoic acid	1072:1092	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	8	50	from	activity	1770:1777	arg1	herb					1807:1810	G. aparine herb	1796:1810	G. aparine herb	1796:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	3	51	theme	polyphenols	529:539	arg1	contents					468:475	The contents	464:475	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols	464:539	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols were determined spectrophotometrically, with extractives and polysaccharides quantified gravimetrically.
31775336	7	52	theme	aparine	1529:1535	arg1	extracts					1552:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts	1522:1559	All G. aparine herb ethanolic extracts stimulate the transformational activity of immunocompetent blood cells, with 96% ethanolic extract being the most active.
31775336	8	53	from	herb	1807:1810	arg1	extracts					1782:1789	extracts	1782:1789	extracts from G. aparine herb	1782:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	8	53	from	herb	1807:1810	arg1	activity					1770:1777	immunomodulatory activity	1753:1777	immunomodulatory activity of extracts from G. aparine herb	1753:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	3	54	theme	flavonoids	514:523	arg1	contents					468:475	The contents	464:475	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols	464:539	The contents of hydroxycinnamic acid derivatives, flavonoids and polyphenols were determined spectrophotometrically, with extractives and polysaccharides quantified gravimetrically.
31775336	4	55	theme	UHPLC-DAD-MS/MS	692:706	arg1	analysis					708:715	UHPLC-DAD-MS/MS analysis	692:715	UHPLC-DAD-MS/MS analysis	692:715	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	4	56	theme	aparine	759:765	arg1	rhamnoglucoside					777:791	G. aparine quercetin rhamnoglucoside	756:791	G. aparine quercetin rhamnoglucoside	756:791	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	0	57	theme	Extracts	75:82	arg1	Activity					53:60	In Vitro Immunomodulatory Activity	27:60	In Vitro Immunomodulatory Activity	27:60	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	57	theme	Extracts	75:82	arg1	Profiles					14:21	Phytochemical Profiles	0:21	Phytochemical Profiles	0:21	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	57	theme	Extracts	75:82	arg1	species					163:169	a widely spread species	147:169	a widely spread species in the Galium genus	147:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	5	58	theme	hydroxycinnamic	1095:1109	arg1	derivatives					1116:1126	hydroxycinnamic acid derivatives	1095:1126	hydroxycinnamic acid derivatives	1095:1126	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	2	59	theme	%	441:441	arg1	ethanol					455:461	20%, 60% or 96% ethanol	439:461	20%, 60% or 96% ethanol	439:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	0	60	from	Profiles	14:21	arg1	L.					122:123	L.	122:123	L.	122:123	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	60	from	Profiles	14:21	arg1	Rubiaceae					133:141	family Rubiaceae	126:141	family Rubiaceae	126:141	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	5	61	theme	isorhamnetin	1356:1367	arg1	3-O-glucorhamnoside					1369:1387	isorhamnetin 3-O-glucorhamnoside	1356:1387	isorhamnetin 3-O-glucorhamnoside	1356:1387	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	2	62	theme	%	453:453	arg1	ethanol					455:461	20%, 60% or 96% ethanol	439:461	20%, 60% or 96% ethanol	439:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	5	63	dep	acids	1246:1250	arg1	i.e.					1129:1132	i.e.	1129:1132	i.e.	1129:1132	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	5	64	dep	Major	953:957	arg1	constitutes					959:969	constitutes	959:969	constitutes	959:969	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	4	65	theme	G.	756:757	arg1	rhamnoglucoside					777:791	G. aparine quercetin rhamnoglucoside	756:791	G. aparine quercetin rhamnoglucoside	756:791	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	5	66	theme	3-O-caffeoylquinic	1135:1152	arg1	acids					1246:1250	4,5-O-dicaffeoylquinic acids	1223:1250	4,5-O-dicaffeoylquinic acids	1223:1250	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	4	67	theme	quercetin	767:775	arg1	rhamnoglucoside					777:791	G. aparine quercetin rhamnoglucoside	756:791	G. aparine quercetin rhamnoglucoside	756:791	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	2	68	theme	G.	352:353	arg1	extracts					378:385	G. aparine herb ethanolic extracts	352:385	G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol	352:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	5	69	theme	5-O-caffeoylquinic	1155:1172	arg1	acids					1246:1250	4,5-O-dicaffeoylquinic acids	1223:1250	4,5-O-dicaffeoylquinic acids	1223:1250	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	2	70	theme	plant	405:409	arg1	material					411:418	the plant material	401:418	the plant material	401:418	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	0	71	theme	In	27:28	arg1	Activity					53:60	In Vitro Immunomodulatory Activity	27:60	In Vitro Immunomodulatory Activity	27:60	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	71	theme	In	27:28	arg1	species					163:169	a widely spread species	147:169	a widely spread species in the Galium genus	147:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	71	theme	In	27:28	arg1	Profiles					14:21	Phytochemical Profiles	0:21	Phytochemical Profiles	0:21	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	5	72	theme	acid	1264:1267	arg1	derivatives					1269:1279	caffeic acid derivatives	1256:1279	caffeic acid derivatives	1256:1279	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	5	73	theme	extracts	974:981	arg1	Major					953:957	Major	953:957	Major	953:957	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	0	74	from	species	163:169	arg1	genus					185:189	the Galium genus	174:189	the Galium genus	174:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	2	75	theme	extracts	378:385	arg1	composition					305:315	chemical composition	296:315	chemical composition	296:315	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	2	75	theme	extracts	378:385	arg1	activities					338:347	immunomodulatory activities	321:347	immunomodulatory activities	321:347	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	0	76	theme	Immunomodulatory	36:51	arg1	Activity					53:60	In Vitro Immunomodulatory Activity	27:60	In Vitro Immunomodulatory Activity	27:60	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	76	theme	Immunomodulatory	36:51	arg1	species					163:169	a widely spread species	147:169	a widely spread species in the Galium genus	147:189	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	0	76	theme	Immunomodulatory	36:51	arg1	Profiles					14:21	Phytochemical Profiles	0:21	Phytochemical Profiles	0:21	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	1	77	theme	supplements	252:262	arg1	part					218:221	part	218:221	part of folk remedies and dietary supplements	218:262	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	1	77	theme	supplements	252:262	arg1	herb					196:199	The herb	192:199	The herb of G. aparine	192:213	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	4	78	theme	column	817:822	arg1	chromatography					824:837	column chromatography	817:837	column chromatography	817:837	The qualitative composition was studied using UHPLC-DAD-MS/MS analysis; isolation not previously described in G. aparine quercetin rhamnoglucoside was carried out through column chromatography, and the immunomodulatory activity of extracts was determined in the reaction of lymphocyte blast transformation.
31775336	2	79	theme	herb	363:366	arg1	extracts					378:385	G. aparine herb ethanolic extracts	352:385	G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol	352:461	In this study, we analyzed the chemical composition and immunomodulatory activities of G. aparine herb ethanolic extracts obtained from the plant material by maceration with 20%, 60% or 96% ethanol.
31775336	5	80	theme	4,5-O-dicaffeoylquinic	1223:1244	arg1	acids					1246:1250	4,5-O-dicaffeoylquinic acids	1223:1250	4,5-O-dicaffeoylquinic acids	1223:1250	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	0	81	dep	In	27:28	arg1	Vitro					30:34	Vitro	30:34	Vitro	30:34	Phytochemical Profiles and In Vitro Immunomodulatory Activity of Ethanolic Extracts from Galium aparine L. Galium aparine L., family Rubiaceae, is a widely spread species in the Galium genus.
31775336	8	82	theme	activity	1770:1777	arg1	mechanisms					1739:1748	the mechanisms	1735:1748	the mechanisms of immunomodulatory activity of extracts from G. aparine herb	1735:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	5	83	theme	10-desacetylasperulosidic	1017:1041	arg1	acid					1043:1046	10-desacetylasperulosidic acid	1017:1046	10-desacetylasperulosidic acid	1017:1046	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	8	84	theme	extracts	1782:1789	arg1	activity					1770:1777	immunomodulatory activity	1753:1777	immunomodulatory activity of extracts from G. aparine herb	1753:1810	The data obtained necessitate further research into the mechanisms of immunomodulatory activity of extracts from G. aparine herb.
31775336	5	85	theme	quercetin	1307:1315	arg1	3-O-rhamnoglucoside-7-O-glucoside					1317:1349	quercetin 3-O-rhamnoglucoside-7-O-glucoside	1307:1349	quercetin 3-O-rhamnoglucoside-7-O-glucoside	1307:1349	Major constitutes of extracts were iridoids, i.e., monotropein, 10-desacetylasperulosidic acid and asperulosidic acid; p-hydroxybenzoic acid; hydroxycinnamic acid derivatives, i.e., 3-O-caffeoylquinic, 5-O-caffeoylquinic, 3,4-O-dicaffeoylquinic, 3,5-O-dicaffeoylquinic, 4,5-O-dicaffeoylquinic acids and caffeic acid derivatives; flavonoids, i.e., rutin, quercetin 3-O-rhamnoglucoside-7-O-glucoside, and isorhamnetin 3-O-glucorhamnoside.
31775336	1	86	theme	aparine	207:213	arg1	part					218:221	part	218:221	part of folk remedies and dietary supplements	218:262	The herb of G. aparine is part of folk remedies and dietary supplements.
31775336	1	86	theme	aparine	207:213	arg1	herb					196:199	The herb	192:199	The herb of G. aparine	192:213	The herb of G. aparine is part of folk remedies and dietary supplements.
30371162	7	0	theme	function	1190:1197	arg1	recovery					1167:1174	poorer recovery	1160:1174	poorer recovery of neurologic function	1160:1197	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	0	theme	function	1190:1197	arg1	damage					1124:1129	more severe tissue damage	1105:1129	more severe tissue damage in the brain and kidney	1105:1153	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	0	theme	function	1190:1197	arg1	rates					1098:1102	trended lower survival rates	1075:1102	trended lower survival rates	1075:1102	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	10	1	theme	Conclusions	1574:1584	arg1	Results					1586:1592	Conclusions Results	1574:1592	Conclusions Results	1574:1592	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	11	2	theme	pathways	1905:1912	arg1	impairment					1870:1879	aging-related impairment	1856:1879	aging-related impairment of proteostasis-related pathways after CA / CPR	1856:1927	Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
30371162	4	3	theme	neurologic	690:699	arg1	deficits					701:708	neurologic deficits	690:708	neurologic deficits	690:708	Functional outcome and organ damage were evaluated by assessing neurologic deficits, histological features, and creatinine level.
30371162	5	4	theme	CPR	761:763	arg1	changes					774:780	CA / CPR -related changes	756:780	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response	756:876	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	6	5	used	used	982:985	arg2	Thiamet-G					968:976	Thiamet-G	968:976	Thiamet-G	968:976	Thiamet-G was used to increase O-linked β-N-acetylglucosamine modification.
30371162	3	6	theme	aged	520:523	arg1	mice					557:560	Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	493:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	473:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	4	7	theme	organ	649:653	arg1	damage					655:660	organ damage	649:660	organ damage	649:660	Functional outcome and organ damage were evaluated by assessing neurologic deficits, histological features, and creatinine level.
30371162	10	8	theme	impaired	1607:1614	arg1	activation					1616:1625	impaired activation	1607:1625	impaired activation of prosurvival pathways	1607:1649	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	7	9	theme	aged	1061:1064	arg1	mice					1066:1069	aged mice	1061:1069	aged mice	1061:1069	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	3	10	theme	C57Bl/6	549:555	arg1	mice					557:560	Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	493:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	473:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	5	11	theme	protein	861:867	arg1	response					869:876	the unfolded protein response	848:876	the unfolded protein response	848:876	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	4	12	theme	histological	711:722	arg1	features					724:731	histological features	711:731	histological features	711:731	Functional outcome and organ damage were evaluated by assessing neurologic deficits, histological features, and creatinine level.
30371162	10	13	theme	cells	1775:1779	arg1	survival					1763:1770	the survival	1759:1770	the survival of cells stressed by ischemia	1759:1800	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	10	14	theme	pathways	1642:1649	arg1	activation					1616:1625	impaired activation	1607:1625	impaired activation of prosurvival pathways	1607:1649	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	7	15	theme	CA	1050:1051	arg1	CPR					1055:1057	CA / CPR	1050:1057	CA / CPR	1050:1057	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	8	16	theme	ubiquitin-like	1244:1257	arg1	conjugation					1268:1278	small ubiquitin-like modifier conjugation	1238:1278	small ubiquitin-like modifier conjugation	1238:1278	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	11	17	theme	pharmacologic	1816:1828	arg1	intervention					1830:1841	a pharmacologic intervention	1814:1841	a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR	1814:1927	Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
30371162	5	18	theme	mRNA	905:908	arg1	levels					922:927	mRNA and protein levels	905:927	mRNA and protein levels in the brain, kidney, and spinal cord	905:965	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	8	19	link	O-linked	1328:1335	arg1	modification					1359:1370	O-linked β-N-acetylglucosamine modification	1328:1370	O-linked β-N-acetylglucosamine modification	1328:1370	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	7	20	from	recovery	1167:1174	arg1	kidney					1148:1153	kidney	1148:1153	kidney	1148:1153	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	20	from	recovery	1167:1174	arg1	brain					1138:1142	brain	1138:1142	brain	1138:1142	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	5	21	theme	protein	914:920	arg1	levels					922:927	mRNA and protein levels	905:927	mRNA and protein levels in the brain, kidney, and spinal cord	905:965	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	0	22	from	Arrest	99:104	arg1	Mice					109:112	Mice	109:112	Mice	109:112	Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.
30371162	7	23	theme	neurologic	1179:1188	arg1	function					1190:1197	neurologic function	1179:1197	neurologic function	1179:1197	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	1	24	from	age	178:180	arg1	outcome					158:164	worse outcome	152:164	worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation	152:226	Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood.
30371162	9	25	theme	increasing	1492:1501	arg1	modification					1534:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification	1474:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA	1474:1554	Finally, pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA improved outcome.
30371162	8	26	theme	unfolded	1297:1304	arg1	response					1314:1321	unfolded protein response	1297:1321	unfolded protein response	1297:1321	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	5	27	theme	CA	756:757	arg1	changes					774:780	CA / CPR -related changes	756:780	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response	756:876	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	1	28	theme	advanced	169:176	arg1	age					178:180	advanced age	169:180	advanced age	169:180	Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood.
30371162	1	29	dep	Background	115:124	arg1	understood					241:250	understood	241:250	are not well understood	228:250	Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood.
30371162	3	30	dep	Young	493:497	arg1	old					511:513	old	511:513	old	511:513	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	3	30	dep	Young	493:497	arg1	old					539:541	old	539:541	old	539:541	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	8	31	theme	β-N-acetylglucosamine	1337:1357	arg1	modification					1359:1370	O-linked β-N-acetylglucosamine modification	1328:1370	O-linked β-N-acetylglucosamine modification	1328:1370	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	10	32	theme	worse	1666:1670	arg1	outcome					1672:1678	worse outcome	1666:1678	worse outcome after CA / CPR in aged mice	1666:1706	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	5	33	theme	small	785:789	arg1	conjugation					815:825	small ubiquitin-like modifier conjugation	785:825	small ubiquitin-like modifier conjugation	785:825	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	2	34	theme	proteostasis-related	410:429	arg1	pathways					443:450	proteostasis-related prosurvival pathways	410:450	proteostasis-related prosurvival pathways activated after CA	410:469	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	2	35	theme	age	403:405	arg1	effects					392:398	the effects	388:398	the effects of age on proteostasis-related prosurvival pathways activated after CA	388:469	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	5	36	theme	modifier	806:813	arg1	conjugation					815:825	small ubiquitin-like modifier conjugation	785:825	small ubiquitin-like modifier conjugation	785:825	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	11	37	theme	promising	1945:1953	arg1	strategy					1967:1974	a promising therapeutic strategy	1943:1974	a promising therapeutic strategy	1943:1974	Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
30371162	7	38	theme	tissue	1117:1122	arg1	damage					1124:1129	more severe tissue damage	1105:1129	more severe tissue damage in the brain and kidney	1105:1153	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	0	39	theme	Impaired	25:32	arg1	Activation					34:43	Impaired Activation	25:43	Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice	25:112	Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.
30371162	6	40	theme	O-linked	999:1006	arg1	modification					1030:1041	O-linked β-N-acetylglucosamine modification	999:1041	O-linked β-N-acetylglucosamine modification	999:1041	Thiamet-G was used to increase O-linked β-N-acetylglucosamine modification.
30371162	0	41	theme	Homeostasis-Related	56:74	arg1	Pathways					76:83	Protein Homeostasis-Related Pathways	48:83	Protein Homeostasis-Related Pathways	48:83	Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.
30371162	7	42	from	rates	1098:1102	arg1	kidney					1148:1153	kidney	1148:1153	kidney	1148:1153	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	42	from	rates	1098:1102	arg1	brain					1138:1142	brain	1138:1142	brain	1138:1142	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	2	43	theme	organismal	326:335	arg1	health					337:342	cellular and organismal health	313:342	cellular and organismal health	313:342	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	2	44	from	effects	392:398	arg1	pathways					443:450	proteostasis-related prosurvival pathways	410:450	proteostasis-related prosurvival pathways activated after CA	410:469	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	11	45	theme	therapeutic	1955:1965	arg1	strategy					1967:1974	a promising therapeutic strategy	1943:1974	a promising therapeutic strategy	1943:1974	Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
30371162	11	46	theme	CA	1920:1921	arg1	CPR					1925:1927	CA / CPR	1920:1927	CA / CPR	1920:1927	Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
30371162	0	47	theme	Protein	48:54	arg1	Pathways					76:83	Protein Homeostasis-Related Pathways	48:83	Protein Homeostasis-Related Pathways	48:83	Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.
30371162	7	48	theme	young	1213:1217	arg1	mice					1219:1222	young mice	1213:1222	young mice	1213:1222	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	49	theme	poorer	1160:1165	arg1	recovery					1167:1174	poorer recovery	1160:1174	poorer recovery of neurologic function	1160:1197	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	50	theme	survival	1089:1096	arg1	rates					1098:1102	trended lower survival rates	1075:1102	trended lower survival rates	1075:1102	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	10	51	theme	proteostasis	1731:1742	arg1	restoration					1716:1726	restoration	1716:1726	restoration of proteostasis	1716:1742	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	7	52	theme	trended	1075:1081	arg1	rates					1098:1102	trended lower survival rates	1075:1102	trended lower survival rates	1075:1102	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	2	53	theme	cellular	313:320	arg1	health					337:342	cellular and organismal health	313:342	cellular and organismal health	313:342	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	6	54	link	O-linked	999:1006	arg1	modification					1030:1041	O-linked β-N-acetylglucosamine modification	999:1041	O-linked β-N-acetylglucosamine modification	999:1041	Thiamet-G was used to increase O-linked β-N-acetylglucosamine modification.
30371162	5	55	theme	unfolded	852:859	arg1	response					869:876	the unfolded protein response	848:876	the unfolded protein response	848:876	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	4	56	theme	Functional	626:635	arg1	outcome					637:643	Functional outcome	626:643	Functional outcome	626:643	Functional outcome and organ damage were evaluated by assessing neurologic deficits, histological features, and creatinine level.
30371162	7	57	dep	trended	1075:1081	arg1	lower					1083:1087	lower	1083:1087	lower	1083:1087	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	3	58	theme	male	544:547	arg1	mice					557:560	Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	493:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	473:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	1	59	theme	cardiac	188:194	arg1	CA					205:206	CA	205:206	CA	205:206	Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood.
30371162	1	59	theme	cardiac	188:194	arg1	arrest					196:201	cardiac arrest	188:201	cardiac arrest ( CA )	188:208	Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood.
30371162	9	60	theme	β-N-acetylglucosamine	1512:1532	arg1	modification					1534:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification	1474:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA	1474:1554	Finally, pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA improved outcome.
30371162	3	61	theme	cardiopulmonary	587:601	arg1	CPR					619:621	CPR	619:621	CPR	619:621	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	3	61	theme	cardiopulmonary	587:601	arg1	resuscitation					603:615	CA and cardiopulmonary resuscitation	580:615	resuscitation	603:615	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	8	62	from	CPR	1398:1400	arg1	mice					1411:1414	young mice	1405:1414	young mice	1405:1414	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	10	63	theme	prosurvival	1630:1640	arg1	pathways					1642:1649	prosurvival pathways	1630:1649	prosurvival pathways	1630:1649	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	8	64	theme	small	1238:1242	arg1	conjugation					1268:1278	small ubiquitin-like modifier conjugation	1238:1278	small ubiquitin-like modifier conjugation	1238:1278	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	2	65	theme	protein	261:267	arg1	proteostasis					282:293	proteostasis	282:293	proteostasis	282:293	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	2	65	theme	protein	261:267	arg1	homeostasis					269:279	protein homeostasis	261:279	protein homeostasis (proteostasis)	261:294	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	8	66	theme	aged	1454:1457	arg1	mice					1459:1462	aged mice	1454:1462	aged mice	1454:1462	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	8	67	theme	modifier	1259:1266	arg1	conjugation					1268:1278	small ubiquitin-like modifier conjugation	1238:1278	small ubiquitin-like modifier conjugation	1238:1278	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	7	68	contain	had	1071:1073	arg1	mice					1066:1069	aged mice	1061:1069	aged mice	1061:1069	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	68	contain	had	1071:1073	arg2	rates					1098:1102	trended lower survival rates	1075:1102	trended lower survival rates	1075:1102	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	68	contain	had	1071:1073	arg2	recovery					1167:1174	poorer recovery	1160:1174	poorer recovery of neurologic function	1160:1197	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	68	contain	had	1071:1073	arg2	damage					1124:1129	more severe tissue damage	1105:1129	more severe tissue damage in the brain and kidney	1105:1153	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	11	69	theme	aging-related	1856:1868	arg1	impairment					1870:1879	aging-related impairment	1856:1879	aging-related impairment of proteostasis-related pathways after CA / CPR	1856:1927	Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
30371162	0	70	theme	Pathways	76:83	arg1	Activation					34:43	Impaired Activation	25:43	Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice	25:112	Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.
30371162	3	71	theme	CA	580:581	arg1	CPR					619:621	CPR	619:621	CPR	619:621	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	3	71	theme	CA	580:581	arg1	resuscitation					603:615	CA and cardiopulmonary resuscitation	580:615	resuscitation	603:615	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	1	72	theme	worse	152:156	arg1	outcome					158:164	worse outcome	152:164	worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation	152:226	Background The mechanisms underlying worse outcome at advanced age after cardiac arrest ( CA ) and resuscitation are not well understood.
30371162	5	73	dep	brain	936:940	arg1	the					932:934	the	932:934	the	932:934	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	0	74	theme	Cardiac	91:97	arg1	Arrest					99:104	Cardiac Arrest	91:104	Cardiac Arrest in Mice	91:112	Aging Is Associated With Impaired Activation of Protein Homeostasis-Related Pathways After Cardiac Arrest in Mice.
30371162	5	75	from	changes	774:780	arg1	ubiquitination					828:841	ubiquitination	828:841	ubiquitination	828:841	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	5	75	from	changes	774:780	arg1	response					869:876	the unfolded protein response	848:876	the unfolded protein response	848:876	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	5	75	from	changes	774:780	arg1	conjugation					815:825	small ubiquitin-like modifier conjugation	785:825	small ubiquitin-like modifier conjugation	785:825	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	9	76	theme	O-linked	1503:1510	arg1	modification					1534:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification	1474:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA	1474:1554	Finally, pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA improved outcome.
30371162	3	77	dep	Methods	473:479	arg1	mice					557:560	Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	493:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	473:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	7	78	from	damage	1124:1129	arg1	kidney					1148:1153	kidney	1148:1153	kidney	1148:1153	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	7	78	from	damage	1124:1129	arg1	brain					1138:1142	brain	1138:1142	brain	1138:1142	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	4	79	theme	creatinine	738:747	arg1	level					749:753	creatinine level	738:753	creatinine level	738:753	Functional outcome and organ damage were evaluated by assessing neurologic deficits, histological features, and creatinine level.
30371162	8	80	theme	protein	1306:1312	arg1	response					1314:1321	unfolded protein response	1297:1321	unfolded protein response	1297:1321	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	2	81	theme	prosurvival	431:441	arg1	pathways					443:450	proteostasis-related prosurvival pathways	410:450	proteostasis-related prosurvival pathways activated after CA	410:469	Because protein homeostasis (proteostasis) is essential for cellular and organismal health, but is impaired after CA , we investigated the effects of age on proteostasis-related prosurvival pathways activated after CA .
30371162	8	82	theme	O-linked	1328:1335	arg1	modification					1359:1370	O-linked β-N-acetylglucosamine modification	1328:1370	O-linked β-N-acetylglucosamine modification	1328:1370	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	5	83	theme	ubiquitin-like	791:804	arg1	conjugation					815:825	small ubiquitin-like modifier conjugation	785:825	small ubiquitin-like modifier conjugation	785:825	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	9	84	link	O-linked	1503:1510	arg1	modification					1534:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification	1474:1545	pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA	1474:1554	Finally, pharmacologically increasing O-linked β-N-acetylglucosamine modification after CA improved outcome.
30371162	7	85	theme	severe	1110:1115	arg1	damage					1124:1129	more severe tissue damage	1105:1129	more severe tissue damage in the brain and kidney	1105:1153	After CA / CPR , aged mice had trended lower survival rates, more severe tissue damage in the brain and kidney, and poorer recovery of neurologic function compared with young mice.
30371162	6	86	theme	β-N-acetylglucosamine	1008:1028	arg1	modification					1030:1041	O-linked β-N-acetylglucosamine modification	999:1041	O-linked β-N-acetylglucosamine modification	999:1041	Thiamet-G was used to increase O-linked β-N-acetylglucosamine modification.
30371162	10	87	theme	CA	1686:1687	arg1	CPR					1691:1693	CA / CPR	1686:1693	CA / CPR	1686:1693	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	5	88	theme	-related	765:772	arg1	changes					774:780	CA / CPR -related changes	756:780	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response	756:876	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	8	89	theme	CA	1393:1394	arg1	CPR					1398:1400	CA / CPR	1393:1400	CA / CPR in young mice	1393:1414	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
30371162	3	90	theme	Young	493:497	arg1	mice					557:560	Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	493:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice	473:560	Methods and Results Young (2-3 months old) and aged (21-22 months old) male C57Bl/6 mice were subjected to CA and cardiopulmonary resuscitation ( CPR ).
30371162	11	91	theme	proteostasis-related	1884:1903	arg1	pathways					1905:1912	proteostasis-related pathways	1884:1912	proteostasis-related pathways	1884:1912	Therefore, a pharmacologic intervention that targets aging-related impairment of proteostasis-related pathways after CA / CPR may represent a promising therapeutic strategy.
30371162	5	92	theme	spinal	955:960	arg1	cord					962:965	spinal cord	955:965	spinal cord	955:965	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	10	93	from	outcome	1672:1678	arg1	mice					1703:1706	aged mice	1698:1706	aged mice	1698:1706	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	10	94	theme	aged	1698:1701	arg1	mice					1703:1706	aged mice	1698:1706	aged mice	1698:1706	Conclusions Results suggest that impaired activation of prosurvival pathways contributes to worse outcome after CA / CPR in aged mice because restoration of proteostasis is critical to the survival of cells stressed by ischemia.
30371162	5	95	from	levels	922:927	arg1	kidney					943:948	kidney	943:948	kidney	943:948	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	5	95	from	levels	922:927	arg1	brain					936:940	brain	936:940	brain	936:940	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	5	95	from	levels	922:927	arg1	cord					962:965	spinal cord	955:965	spinal cord	955:965	CA / CPR -related changes in small ubiquitin-like modifier conjugation, ubiquitination, and the unfolded protein response were analyzed by measuring mRNA and protein levels in the brain, kidney, and spinal cord.
30371162	8	96	theme	young	1405:1409	arg1	mice					1411:1414	young mice	1405:1414	young mice	1405:1414	Furthermore, small ubiquitin-like modifier conjugation, ubiquitination, unfolded protein response, and O-linked β-N-acetylglucosamine modification were activated after CA / CPR in young mice, but their activation was impaired in aged mice.
31887507	7	0	theme	Environmental	1310:1322	arg1	process					1324:1330	Environmental process	1310:1330	Environmental process	1310:1330	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	6	1	contain	contained	1212:1220	arg2	groups					1272:1277	hydroxyl, carboxyl, amide and carbonyl functional groups	1222:1277	groups	1272:1277	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	6	1	contain	contained	1212:1220	arg1	fractions					1202:1210	original- and environmental GRSP fractions	1169:1210	original- and environmental GRSP fractions	1169:1210	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	3	2	theme	arbuscular	693:702	arg1	fungi					716:720	three arbuscular mycorrhizal fungi	687:720	three arbuscular mycorrhizal fungi	687:720	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	1	3	theme	terrestrial	251:261	arg1	quality					268:274	terrestrial soil quality	251:274	terrestrial soil quality	251:274	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	4	4	theme	mangrove	910:917	arg1	wetlands					919:926	major subtropical and tropical mangrove wetlands	879:926	major subtropical and tropical mangrove wetlands in southern China	879:944	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	7	5	theme	relative	1427:1434	arg1	content					1436:1442	the relative content	1423:1442	the relative content of the functional groups	1423:1467	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	6	6	theme	carbonyl	1252:1259	arg1	groups					1272:1277	hydroxyl, carboxyl, amide and carbonyl functional groups	1222:1277	groups	1272:1277	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	6	7	theme	amide	1242:1246	arg1	groups					1272:1277	hydroxyl, carboxyl, amide and carbonyl functional groups	1222:1277	groups	1272:1277	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	3	8	theme	Glomus	723:728	arg1	intraradices					730:741	Glomus intraradices	723:741	Glomus intraradices	723:741	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	10	9	theme	GRSP	1852:1855	arg1	fingerprints					1866:1877	GRSP infrared fingerprints	1852:1877	GRSP infrared fingerprints coupled with multivariate analyses	1852:1912	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	1	10	theme	glomalin-related	178:193	arg1	GRSP					209:212	GRSP	209:212	GRSP	209:212	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	1	10	theme	glomalin-related	178:193	arg1	protein					200:206	glomalin-related soil protein	178:206	glomalin-related soil protein (GRSP)	178:213	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	4	11	theme	major	879:883	arg1	wetlands					919:926	major subtropical and tropical mangrove wetlands	879:926	major subtropical and tropical mangrove wetlands in southern China	879:944	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	6	12	theme	carboxyl	1232:1239	arg1	groups					1272:1277	hydroxyl, carboxyl, amide and carbonyl functional groups	1222:1277	groups	1272:1277	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	10	13	theme	contributing	2028:2039	arg1	sources					2041:2047	contributing sources	2028:2047	contributing sources	2028:2047	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	3	14	theme	Acaulospora	766:776	arg1	laevis					778:783	Acaulospora laevis	766:783	Acaulospora laevis	766:783	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	9	15	theme	functional	1748:1757	arg1	contents					1765:1772	functional group contents	1748:1772	functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids	1748:1846	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	3	16	attach	derived	674:680	arg1	fungi					716:720	three arbuscular mycorrhizal fungi	687:720	three arbuscular mycorrhizal fungi	687:720	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	3	16	attach	derived	674:680	arg1	intraradices					730:741	Glomus intraradices	723:741	Glomus intraradices	723:741	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	3	16	attach	derived	674:680	arg1	versiforme					751:760	Glomus versiforme	744:760	Glomus versiforme	744:760	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	3	16	attach	derived	674:680	arg1	laevis					778:783	Acaulospora laevis	766:783	Acaulospora laevis	766:783	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	3	16	attach	derived	674:680	arg2	GRSP					669:672	original GRSP	660:672	original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis	660:783	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	6	17	theme	hydroxyl	1222:1229	arg1	groups					1272:1277	hydroxyl, carboxyl, amide and carbonyl functional groups	1222:1277	groups	1272:1277	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	9	18	theme	group	1759:1763	arg1	contents					1765:1772	functional group contents	1748:1772	functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids	1748:1846	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	2	19	theme	environmental	521:533	arg1	conditions					535:544	environmental conditions	521:544	environmental conditions	521:544	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	2	20	from	soils	468:472	arg1	patterns					419:426	the metal sequestration patterns	395:426	the metal sequestration patterns of GRSP in both terrestrial and aquatic soils	395:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	3	21	theme	microcosm	596:604	arg1	experiments					606:616	microcosm experiments	596:616	microcosm experiments	596:616	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	9	22	theme	nucleic	1834:1840	arg1	acids					1842:1846	nucleic acids	1834:1846	nucleic acids	1834:1846	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	8	23	theme	environmental	1521:1533	arg1	GRSP					1535:1538	original- and environmental GRSP	1507:1538	original- and environmental GRSP	1507:1538	The infrared fingerprint analyses of original- and environmental GRSP revealed field-specific, however, no taxon-specific characteristics of GRSP.
31887507	6	24	theme	metal	1295:1299	arg1	binding					1301:1307	metal binding	1295:1307	metal binding	1295:1307	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	5	25	theme	GRSP-bound	947:956	arg1	metals					958:963	GRSP-bound metals	947:963	GRSP-bound metals	947:963	GRSP-bound metals were significantly and positively correlated with total metals, and the metal binding contributed to the metal sequestration of mangrove soils.
31887507	5	26	theme	mangrove	1093:1100	arg1	soils					1102:1106	mangrove soils	1093:1106	mangrove soils	1093:1106	GRSP-bound metals were significantly and positively correlated with total metals, and the metal binding contributed to the metal sequestration of mangrove soils.
31887507	1	27	theme	particles	154:162	arg1	binding					135:141	binding	135:141	binding of mineral particles and elements	135:175	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	2	28	from	patterns	419:426	arg1	soils					468:472	both terrestrial and aquatic soils	439:472	both terrestrial and aquatic soils	439:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	2	29	theme	GRSP	556:559	arg1	characteristics					561:575	GRSP characteristics	556:575	GRSP characteristics	556:575	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	0	30	theme	pollution	71:79	arg1	bioindicators					81:93	soil pollution bioindicators	66:93	soil pollution bioindicators in mangrove wetland ecosystems	66:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	1	31	theme	aquatic	336:342	arg1	ecosystems					344:353	aquatic ecosystems	336:353	aquatic ecosystems	336:353	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	1	32	theme	elements	168:175	arg1	binding					135:141	binding	135:141	binding of mineral particles and elements	135:175	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	8	33	theme	taxon-specific	1577:1590	arg1	characteristics					1592:1606	no taxon-specific characteristics	1574:1606	no taxon-specific characteristics of GRSP	1574:1614	The infrared fingerprint analyses of original- and environmental GRSP revealed field-specific, however, no taxon-specific characteristics of GRSP.
31887507	5	34	theme	total	1015:1019	arg1	metals					1021:1026	total metals	1015:1026	total metals	1015:1026	GRSP-bound metals were significantly and positively correlated with total metals, and the metal binding contributed to the metal sequestration of mangrove soils.
31887507	0	35	theme	wetland	107:113	arg1	ecosystems					115:124	mangrove wetland ecosystems	98:124	mangrove wetland ecosystems	98:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	9	36	theme	GRSP	1648:1651	arg1	composition					1663:1673	the GRSP molecular composition	1644:1673	the GRSP molecular composition	1644:1673	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	6	37	theme	infrared	1127:1134	arg1	results					1149:1155	Fourier-transform infrared spectroscopy results	1109:1155	Fourier-transform infrared spectroscopy results	1109:1155	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	4	38	from	wetlands	919:926	arg1	China					940:944	southern China	931:944	southern China	931:944	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	9	39	theme	composition	1663:1673	arg1	analysis					1632:1639	Biostatistical analysis	1617:1639	Biostatistical analysis of the GRSP molecular composition	1617:1673	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	7	40	theme	GRSP	1386:1389	arg1	groups					1372:1377	functional groups	1361:1377	functional groups of the GRSP	1361:1389	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	7	40	theme	GRSP	1386:1389	arg1	GRSP					1386:1389	the GRSP	1382:1389	the GRSP	1382:1389	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	2	41	theme	sequestration	405:417	arg1	patterns					419:426	the metal sequestration patterns	395:426	the metal sequestration patterns of GRSP in both terrestrial and aquatic soils	395:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	0	42	theme	soil	16:19	arg1	metals					21:26	soil metals	16:26	soil metals	16:26	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	2	43	theme	aquatic	460:466	arg1	soils					468:472	both terrestrial and aquatic soils	439:472	both terrestrial and aquatic soils	439:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	3	44	theme	original	660:667	arg1	GRSP					669:672	original GRSP	660:672	original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis	660:783	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	7	45	theme	functional	1361:1370	arg1	groups					1372:1377	functional groups	1361:1377	functional groups of the GRSP	1361:1389	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	7	45	theme	functional	1361:1370	arg1	GRSP					1386:1389	the GRSP	1382:1389	the GRSP	1382:1389	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	2	46	theme	terrestrial	444:454	arg1	soils					468:472	both terrestrial and aquatic soils	439:472	both terrestrial and aquatic soils	439:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	10	47	theme	heavy	1969:1973	arg1	pollution					1981:1989	heavy metal pollution	1969:1989	heavy metal pollution	1969:1989	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	4	48	theme	GRSP	857:860	arg1	patterns					831:838	the metal sequestration patterns	807:838	the metal sequestration patterns of environmental GRSP	807:860	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	10	49	theme	pollution	1981:1989	arg1	identification					1951:1964	source identification	1944:1964	source identification of heavy metal pollution	1944:1989	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	0	50	theme	soil	50:53	arg1	protein					55:61	glomalin-related soil protein	33:61	glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems	33:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	1	51	theme	elements	307:314	arg1	fate					299:302	the fate	295:302	the fate of elements from terrestrial to aquatic ecosystems	295:353	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	5	52	theme	metal	1070:1074	arg1	sequestration					1076:1088	the metal sequestration	1066:1088	the metal sequestration of mangrove soils	1066:1106	GRSP-bound metals were significantly and positively correlated with total metals, and the metal binding contributed to the metal sequestration of mangrove soils.
31887507	9	53	theme	contents	1765:1772	arg1	ratios					1738:1743	the ratios	1734:1743	the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids	1734:1846	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	6	54	theme	GRSP	1197:1200	arg1	fractions					1202:1210	original- and environmental GRSP fractions	1169:1210	original- and environmental GRSP fractions	1169:1210	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	10	55	theme	reliable	2004:2011	arg1	evidence					2013:2020	more reliable evidence	1999:2020	more reliable evidence about contributing sources	1999:2047	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	8	56	theme	fingerprint	1483:1493	arg1	analyses					1495:1502	The infrared fingerprint analyses	1470:1502	The infrared fingerprint analyses of original- and environmental GRSP	1470:1538	The infrared fingerprint analyses of original- and environmental GRSP revealed field-specific, however, no taxon-specific characteristics of GRSP.
31887507	0	57	with	Interactions	0:11	arg1	protein					55:61	glomalin-related soil protein	33:61	glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems	33:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	4	58	theme	sequestration	817:829	arg1	patterns					831:838	the metal sequestration patterns	807:838	the metal sequestration patterns of environmental GRSP	807:860	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	2	59	theme	little	365:370	arg1	knowledge					372:380	little knowledge	365:380	little knowledge	365:380	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	10	60	theme	metal	1975:1979	arg1	pollution					1981:1989	heavy metal pollution	1969:1989	heavy metal pollution	1969:1989	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	4	61	theme	subtropical	885:895	arg1	wetlands					919:926	major subtropical and tropical mangrove wetlands	879:926	major subtropical and tropical mangrove wetlands in southern China	879:944	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	3	62	theme	mycorrhizal	704:714	arg1	fungi					716:720	three arbuscular mycorrhizal fungi	687:720	three arbuscular mycorrhizal fungi	687:720	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	1	63	from	fate	299:302	arg1	terrestrial					321:331	terrestrial	321:331	terrestrial	321:331	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	1	64	theme	soil	263:266	arg1	quality					268:274	terrestrial soil quality	251:274	terrestrial soil quality	251:274	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	4	65	theme	tropical	901:908	arg1	wetlands					919:926	major subtropical and tropical mangrove wetlands	879:926	major subtropical and tropical mangrove wetlands in southern China	879:944	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	3	66	theme	Glomus	744:749	arg1	versiforme					751:760	Glomus versiforme	744:760	Glomus versiforme	744:760	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	10	67	theme	infrared	1857:1864	arg1	fingerprints					1866:1877	GRSP infrared fingerprints	1852:1877	GRSP infrared fingerprints coupled with multivariate analyses	1852:1912	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	1	68	theme	soil	195:198	arg1	GRSP					209:212	GRSP	209:212	GRSP	209:212	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	1	68	theme	soil	195:198	arg1	protein					200:206	glomalin-related soil protein	178:206	glomalin-related soil protein (GRSP)	178:213	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	9	69	theme	pollution	1706:1714	arg1	sources					1716:1722	the soil pollution sources	1697:1722	the soil pollution sources	1697:1722	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	10	70	theme	multivariate	1892:1903	arg1	analyses					1905:1912	multivariate analyses	1892:1912	multivariate analyses	1892:1912	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	0	71	from	bioindicators	81:93	arg1	ecosystems					115:124	mangrove wetland ecosystems	98:124	mangrove wetland ecosystems	98:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	7	72	theme	groups	1462:1467	arg1	content					1436:1442	the relative content	1423:1442	the relative content of the functional groups	1423:1467	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	9	73	theme	Biostatistical	1617:1630	arg1	analysis					1632:1639	Biostatistical analysis	1617:1639	Biostatistical analysis of the GRSP molecular composition	1617:1673	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	8	74	theme	GRSP	1535:1538	arg1	analyses					1495:1502	The infrared fingerprint analyses	1470:1502	The infrared fingerprint analyses of original- and environmental GRSP	1470:1538	The infrared fingerprint analyses of original- and environmental GRSP revealed field-specific, however, no taxon-specific characteristics of GRSP.
31887507	2	75	from	GRSP	431:434	arg1	soils					468:472	both terrestrial and aquatic soils	439:472	both terrestrial and aquatic soils	439:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	7	76	theme	functional	1451:1460	arg1	groups					1462:1467	the functional groups	1447:1467	the functional groups	1447:1467	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	4	77	theme	southern	931:938	arg1	China					940:944	southern China	931:944	southern China	931:944	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	0	78	theme	soil	66:69	arg1	bioindicators					81:93	soil pollution bioindicators	66:93	soil pollution bioindicators in mangrove wetland ecosystems	66:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	5	79	theme	soils	1102:1106	arg1	sequestration					1076:1088	the metal sequestration	1066:1088	the metal sequestration of mangrove soils	1066:1106	GRSP-bound metals were significantly and positively correlated with total metals, and the metal binding contributed to the metal sequestration of mangrove soils.
31887507	10	80	theme	source	1944:1949	arg1	identification					1951:1964	source identification	1944:1964	source identification of heavy metal pollution	1944:1989	By GRSP infrared fingerprints coupled with multivariate analyses, we developed a technique for source identification of heavy metal pollution, giving more reliable evidence about contributing sources.
31887507	1	81	theme	mineral	146:152	arg1	particles					154:162	mineral particles	146:162	mineral particles	146:162	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	6	82	theme	functional	1261:1270	arg1	groups					1272:1277	hydroxyl, carboxyl, amide and carbonyl functional groups	1222:1277	groups	1272:1277	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	0	83	theme	mangrove	98:105	arg1	ecosystems					115:124	mangrove wetland ecosystems	98:124	mangrove wetland ecosystems	98:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	7	84	contain	had	1332:1334	arg1	process					1324:1330	Environmental process	1310:1330	Environmental process	1310:1330	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	7	84	contain	had	1332:1334	arg2	effect					1339:1344	no effect	1336:1344	no effect	1336:1344	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	8	85	theme	GRSP	1611:1614	arg1	characteristics					1592:1606	no taxon-specific characteristics	1574:1606	no taxon-specific characteristics of GRSP	1574:1614	The infrared fingerprint analyses of original- and environmental GRSP revealed field-specific, however, no taxon-specific characteristics of GRSP.
31887507	6	86	theme	spectroscopy	1136:1147	arg1	results					1149:1155	Fourier-transform infrared spectroscopy results	1109:1155	Fourier-transform infrared spectroscopy results	1109:1155	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	9	87	theme	molecular	1653:1661	arg1	composition					1663:1673	the GRSP molecular composition	1644:1673	the GRSP molecular composition	1644:1673	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	6	88	theme	Fourier-transform	1109:1125	arg1	results					1149:1155	Fourier-transform infrared spectroscopy results	1109:1155	Fourier-transform infrared spectroscopy results	1109:1155	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	2	89	theme	GRSP	431:434	arg1	patterns					419:426	the metal sequestration patterns	395:426	the metal sequestration patterns of GRSP in both terrestrial and aquatic soils	395:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	8	90	theme	original-	1507:1515	arg1	GRSP					1535:1538	original- and environmental GRSP	1507:1538	original- and environmental GRSP	1507:1538	The infrared fingerprint analyses of original- and environmental GRSP revealed field-specific, however, no taxon-specific characteristics of GRSP.
31887507	0	91	theme	metals	21:26	arg1	Interactions					0:11	Interactions	0:11	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.	0:125	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	7	92	theme	groups	1372:1377	arg1	type					1353:1356	the type	1349:1356	the type of functional groups of the GRSP	1349:1389	Environmental process had no effect on the type of functional groups of the GRSP, while it significantly changed the relative content of the functional groups.
31887507	2	93	theme	patterns	419:426	arg1	knowledge					372:380	little knowledge	365:380	little knowledge	365:380	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	2	94	theme	metal	399:403	arg1	patterns					419:426	the metal sequestration patterns	395:426	the metal sequestration patterns of GRSP in both terrestrial and aquatic soils	395:472	There is little knowledge, however, of the metal sequestration patterns of GRSP in both terrestrial and aquatic soils, and this limits progress in understanding how environmental conditions influence GRSP characteristics.
31887507	0	95	theme	glomalin-related	33:48	arg1	protein					55:61	glomalin-related soil protein	33:61	glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems	33:124	Interactions of soil metals with glomalin-related soil protein as soil pollution bioindicators in mangrove wetland ecosystems.
31887507	3	96	theme	molecular	635:643	arg1	composition					645:655	the molecular composition	631:655	the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis	631:783	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	1	97	from	terrestrial	321:331	arg1	elements					307:314	elements	307:314	elements from terrestrial	307:331	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	1	97	from	terrestrial	321:331	arg1	fate					299:302	the fate	295:302	the fate of elements from terrestrial to aquatic ecosystems	295:353	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	9	98	theme	soil	1701:1704	arg1	sources					1716:1722	the soil pollution sources	1697:1722	the soil pollution sources	1697:1722	Biostatistical analysis of the GRSP molecular composition further revealed that the soil pollution sources regulated the ratios of functional group contents associated with hydrocarbons, proteins, polysaccharides and nucleic acids.
31887507	4	99	theme	environmental	843:855	arg1	GRSP					857:860	environmental GRSP	843:860	environmental GRSP	843:860	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31887507	6	100	theme	environmental	1183:1195	arg1	fractions					1202:1210	original- and environmental GRSP fractions	1169:1210	original- and environmental GRSP fractions	1169:1210	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	3	101	theme	GRSP	669:672	arg1	composition					645:655	the molecular composition	631:655	the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis	631:783	Here, we employed microcosm experiments to determine the molecular composition of original GRSP derived from three arbuscular mycorrhizal fungi, Glomus intraradices, Glomus versiforme and Acaulospora laevis.
31887507	8	102	theme	infrared	1474:1481	arg1	analyses					1495:1502	The infrared fingerprint analyses	1470:1502	The infrared fingerprint analyses of original- and environmental GRSP	1470:1538	The infrared fingerprint analyses of original- and environmental GRSP revealed field-specific, however, no taxon-specific characteristics of GRSP.
31887507	1	103	theme	critical	223:230	arg1	role					232:235	a critical role	221:235	a critical role	221:235	Through binding of mineral particles and elements, glomalin-related soil protein (GRSP) plays a critical role in sustaining terrestrial soil quality and contributes to the fate of elements from terrestrial to aquatic ecosystems.
31887507	5	104	theme	metal	1037:1041	arg1	binding					1043:1049	the metal binding	1033:1049	the metal binding	1033:1049	GRSP-bound metals were significantly and positively correlated with total metals, and the metal binding contributed to the metal sequestration of mangrove soils.
31887507	6	105	theme	original-	1169:1177	arg1	fractions					1202:1210	original- and environmental GRSP fractions	1169:1210	original- and environmental GRSP fractions	1169:1210	Fourier-transform infrared spectroscopy results showed that original- and environmental GRSP fractions contained hydroxyl, carboxyl, amide and carbonyl functional groups, which enhanced metal binding.
31887507	4	106	theme	metal	811:815	arg1	patterns					831:838	the metal sequestration patterns	807:838	the metal sequestration patterns of environmental GRSP	807:860	To gain insight into the metal sequestration patterns of environmental GRSP, we investigated major subtropical and tropical mangrove wetlands in southern China.
31101650	4	0	theme	canonical	633:641	arg1	receptor					683:690	the insulin receptor	671:690	the insulin receptor	671:690	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	0	theme	canonical	633:641	arg1	receptor					725:732	insulin-like growth factor 1 receptor	696:732	insulin-like growth factor 1 receptor (IGF-1R)	696:741	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	0	theme	canonical	633:641	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	1	theme	receptor	652:659	arg1	receptor					683:690	the insulin receptor	671:690	the insulin receptor	671:690	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	1	theme	receptor	652:659	arg1	receptor					725:732	insulin-like growth factor 1 receptor	696:732	insulin-like growth factor 1 receptor (IGF-1R)	696:741	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	1	theme	receptor	652:659	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	2	theme	endoplasmic	891:901	arg1	reticulum					903:911	endoplasmic reticulum	891:911	increased endoplasmic reticulum localization	881:924	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	6	3	theme	inhibitor	1250:1258	arg1	NGI-1					1260:1264	the oligosaccharyltransferase inhibitor NGI-1	1220:1264	the oligosaccharyltransferase inhibitor NGI-1	1220:1264	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	8	4	theme	abnormal	1769:1776	arg1	glycosylation					1778:1790	abnormal glycosylation	1769:1790	abnormal glycosylation	1769:1790	These results provide new insight into CDG pathogenesis and highlight how the surface abundance of some glycoproteins can be dually impacted by abnormal glycosylation.
31101650	3	5	theme	glycoproteins	585:597	arg1	presence					535:542	presence	535:542	presence	535:542	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	5	theme	glycoproteins	585:597	arg1	status					562:567	glycosylation status	548:567	glycosylation status	548:567	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	5	6	theme	Providing	927:935	arg1	cDNA					937:940	Providing cDNA	927:940	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a)	927:1015	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	7	7	theme	receptor	1579:1586	arg1	processing					1588:1597	receptor processing	1579:1597	receptor processing	1579:1597	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	2	8	theme	glycosylation	360:372	arg1	disorders					347:355	the congenital disorders	332:355	the congenital disorders of glycosylation (CDG)	332:378	This limits our understanding of pathogenesis in the congenital disorders of glycosylation (CDG).
31101650	7	9	theme	N-linked	1486:1493	arg1	glycosylation					1495:1507	N-linked glycosylation	1486:1507	N-linked glycosylation	1486:1507	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	7	10	theme	receptor	1512:1519	arg1	kinases					1530:1536	receptor tyrosine kinases	1512:1536	receptor tyrosine kinases	1512:1536	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	7	11	theme	glycosylation	1495:1507	arg1	inhibition					1472:1481	STT3A-dependent inhibition	1456:1481	STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases	1456:1558	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	4	12	theme	growth	709:714	arg1	IGF-1R					735:740	IGF-1R	735:740	IGF-1R	735:740	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	12	theme	growth	709:714	arg1	receptor					725:732	insulin-like growth factor 1 receptor	696:732	insulin-like growth factor 1 receptor (IGF-1R)	696:741	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	12	theme	growth	709:714	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	3	13	gly	glycosylation	548:560	arg1	glycoproteins					585:597	cell surface glycoproteins	572:597	cell surface glycoproteins	572:597	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	4	14	theme	cell	752:755	arg1	surface					757:763	the cell surface	748:763	the cell surface	748:763	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	7	15	theme	STT3A-dependent	1456:1470	arg1	inhibition					1472:1481	STT3A-dependent inhibition	1456:1481	STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases	1456:1558	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	1	16	theme	N-linked	113:120	arg1	glycosylation					122:134	N-linked glycosylation	113:134	N-linked glycosylation	113:134	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	0	17	theme	kinase	73:78	arg1	processing					80:89	receptor tyrosine kinase processing	55:89	receptor tyrosine kinase processing	55:89	Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.
31101650	4	18	from	occupancy	824:832	arg1	combination					864:874	combination	864:874	combination with increased endoplasmic reticulum localization	864:924	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	5	19	theme	proprotein	961:970	arg1	convertase					972:981	Golgi-resident proprotein convertase	946:981	Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a)	946:1015	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	6	20	contain	have	1389:1392	arg1	alterations					1337:1347	alterations	1337:1347	alterations in the glycosylation of this convertase	1337:1387	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	6	20	contain	have	1389:1392	arg2	consequences					1405:1416	functional consequences	1394:1416	functional consequences	1394:1416	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	3	21	gly	glycoproteins	585:597	arg1	glycoproteins					585:597	cell surface glycoproteins	572:597	cell surface glycoproteins	572:597	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	5	22	theme	subtilisin/kexin	983:998	arg1	5a					1005:1006	Golgi-resident proprotein convertase subtilisin/kexin type 5a	946:1006	Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a)	946:1015	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	5	22	theme	subtilisin/kexin	983:998	arg1	PCSK5a					1009:1014	PCSK5a	1009:1014	PCSK5a	1009:1014	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	3	23	theme	exo-enzymatic	399:411	arg1	labeling					413:420	selective exo-enzymatic labeling	389:420	selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B -	389:518	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	8	24	theme	new	1647:1649	arg1	insight					1651:1657	new insight	1647:1657	new insight into CDG pathogenesis	1647:1679	These results provide new insight into CDG pathogenesis and highlight how the surface abundance of some glycoproteins can be dually impacted by abnormal glycosylation.
31101650	4	25	theme	decreased	793:801	arg1	occupancy					824:832	decreased N-linked glycan site occupancy	793:832	decreased N-linked glycan site occupancy	793:832	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	8	26	gly	glycoproteins	1729:1741	arg1	glycoproteins					1729:1741	some glycoproteins	1724:1741	some glycoproteins	1724:1741	These results provide new insight into CDG pathogenesis and highlight how the surface abundance of some glycoproteins can be dually impacted by abnormal glycosylation.
31101650	5	27	theme	wild-type	1035:1043	arg1	cells					1056:1060	wild-type and mutant cells	1035:1060	wild-type and mutant cells	1035:1060	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	4	28	theme	glycan	812:817	arg1	occupancy					824:832	decreased N-linked glycan site occupancy	793:832	decreased N-linked glycan site occupancy	793:832	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	3	29	from	deficient	431:439	arg1	subunits					462:469	the two catalytic subunits	444:469	the two catalytic subunits of oligosaccharyltransferase	444:498	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	30	used	used	384:387	arg2	We					381:382	We	381:382	We	381:382	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	5	31	theme	mutant	1049:1054	arg1	cells					1056:1060	wild-type and mutant cells	1035:1060	wild-type and mutant cells	1035:1060	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	3	32	theme	deficient	431:439	arg1	STT3B					512:516	STT3B	512:516	STT3B	512:516	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	32	theme	deficient	431:439	arg1	STT3A					502:506	STT3A	502:506	STT3A	502:506	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	32	theme	deficient	431:439	arg1	cells					425:429	cells	425:429	cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B -	425:518	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	0	33	theme	Selective	0:8	arg1	inhibition					10:19	Selective inhibition	0:19	Selective inhibition of N-linked glycosylation	0:45	Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.
31101650	1	34	theme	glycosylation	122:134	arg1	inhibition					99:108	Global inhibition	92:108	Global inhibition of N-linked glycosylation	92:134	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	3	35	theme	catalytic	452:460	arg1	subunits					462:469	the two catalytic subunits	444:469	the two catalytic subunits of oligosaccharyltransferase	444:498	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	0	36	theme	glycosylation	33:45	arg1	inhibition					10:19	Selective inhibition	0:19	Selective inhibition of N-linked glycosylation	0:45	Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.
31101650	5	37	theme	PCSK5a	1099:1104	arg1	forms					1090:1094	under-glycosylated forms	1071:1094	under-glycosylated forms of PCSK5a, but not furin,	1071:1120	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	0	38	theme	receptor	55:62	arg1	kinase					73:78	receptor tyrosine kinase	55:78	receptor tyrosine kinase processing	55:89	Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.
31101650	4	39	link	N-linked	803:810	arg1	occupancy					824:832	decreased N-linked glycan site occupancy	793:832	decreased N-linked glycan site occupancy	793:832	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	40	from	surface	757:763	arg1	abundance					616:624	reduced abundance	608:624	reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface	608:763	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	2	41	theme	pathogenesis	316:327	arg1	understanding					299:311	our understanding	295:311	our understanding of pathogenesis	295:327	This limits our understanding of pathogenesis in the congenital disorders of glycosylation (CDG).
31101650	4	42	theme	kinases	661:667	arg1	abundance					616:624	reduced abundance	608:624	reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface	608:763	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	1	43	link	N-linked	113:120	arg1	glycosylation					122:134	N-linked glycosylation	113:134	N-linked glycosylation	113:134	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	4	44	theme	proteolytic	838:848	arg1	processing					850:859	proteolytic processing	838:859	proteolytic processing	838:859	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	6	45	theme	convertase	1378:1387	arg1	glycosylation					1356:1368	the glycosylation	1352:1368	the glycosylation of this convertase	1352:1387	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	3	46	theme	glycosylation	548:560	arg1	status					562:567	glycosylation status	548:567	glycosylation status	548:567	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	6	47	from	alterations	1337:1347	arg1	glycosylation					1356:1368	the glycosylation	1352:1368	the glycosylation of this convertase	1352:1387	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	7	48	theme	surface	1603:1609	arg1	localization					1611:1622	surface localization	1603:1622	surface localization	1603:1622	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	0	49	link	N-linked	24:31	arg1	glycosylation					33:45	N-linked glycosylation	24:45	N-linked glycosylation	24:45	Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.
31101650	6	50	theme	Reduced	1146:1152	arg1	glycosylation					1154:1166	Reduced glycosylation	1146:1166	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1	1146:1264	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	2	51	theme	congenital	336:345	arg1	disorders					347:355	the congenital disorders	332:355	the congenital disorders of glycosylation (CDG)	332:378	This limits our understanding of pathogenesis in the congenital disorders of glycosylation (CDG).
31101650	6	52	gly	glycosylation	1356:1368	arg1	convertase					1378:1387	this convertase	1373:1387	this convertase	1373:1387	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	4	53	theme	tyrosine	643:650	arg1	receptor					683:690	the insulin receptor	671:690	the insulin receptor	671:690	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	53	theme	tyrosine	643:650	arg1	receptor					725:732	insulin-like growth factor 1 receptor	696:732	insulin-like growth factor 1 receptor (IGF-1R)	696:741	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	53	theme	tyrosine	643:650	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	3	54	theme	surface	577:583	arg1	glycoproteins					585:597	cell surface glycoproteins	572:597	cell surface glycoproteins	572:597	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	4	55	theme	increased	881:889	arg1	localization					913:924	increased endoplasmic reticulum localization	881:924	increased endoplasmic reticulum localization	881:924	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	6	56	theme	oligosaccharyltransferase	1224:1248	arg1	NGI-1					1260:1264	the oligosaccharyltransferase inhibitor NGI-1	1220:1264	the oligosaccharyltransferase inhibitor NGI-1	1220:1264	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	4	57	theme	factor	716:721	arg1	IGF-1R					735:740	IGF-1R	735:740	IGF-1R	735:740	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	57	theme	factor	716:721	arg1	receptor					725:732	insulin-like growth factor 1 receptor	696:732	insulin-like growth factor 1 receptor (IGF-1R)	696:741	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	57	theme	factor	716:721	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	1	58	gly	glycoproteins	253:265	arg1	glycoproteins					253:265	specific glycoproteins	244:265	specific glycoproteins	244:265	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	4	59	theme	reticulum	903:911	arg1	localization					913:924	increased endoplasmic reticulum localization	881:924	increased endoplasmic reticulum localization	881:924	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	7	60	theme	tyrosine	1521:1528	arg1	kinases					1530:1536	receptor tyrosine kinases	1512:1536	receptor tyrosine kinases	1512:1536	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	1	61	theme	specific	244:251	arg1	glycoproteins					253:265	specific glycoproteins	244:265	specific glycoproteins	244:265	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	4	62	theme	insulin-like	696:707	arg1	IGF-1R					735:740	IGF-1R	735:740	IGF-1R	735:740	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	62	theme	insulin-like	696:707	arg1	receptor					725:732	insulin-like growth factor 1 receptor	696:732	insulin-like growth factor 1 receptor (IGF-1R)	696:741	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	62	theme	insulin-like	696:707	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	1	63	gly	glycoproteins	172:184	arg1	glycoproteins					172:184	glycoproteins	172:184	glycoproteins	172:184	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	5	64	theme	type	1000:1003	arg1	5a					1005:1006	Golgi-resident proprotein convertase subtilisin/kexin type 5a	946:1006	Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a)	946:1015	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	5	64	theme	type	1000:1003	arg1	PCSK5a					1009:1014	PCSK5a	1009:1014	PCSK5a	1009:1014	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	6	65	theme	receptor	1302:1309	arg1	processing					1311:1320	receptor processing	1302:1320	receptor processing	1302:1320	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	6	66	theme	functional	1394:1403	arg1	consequences					1405:1416	functional consequences	1394:1416	functional consequences	1394:1416	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	5	67	theme	furin	1115:1119	arg1	forms					1090:1094	under-glycosylated forms	1071:1094	under-glycosylated forms of PCSK5a, but not furin,	1071:1120	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	4	68	from	processing	850:859	arg1	combination					864:874	combination	864:874	combination with increased endoplasmic reticulum localization	864:924	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	1	69	theme	glycan	152:157	arg1	occupancy					159:167	glycan occupancy	152:167	glycan occupancy on glycoproteins	152:184	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	4	70	with	combination	864:874	arg1	localization					913:924	increased endoplasmic reticulum localization	881:924	increased endoplasmic reticulum localization	881:924	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	71	dep	kinases	661:667	arg1	receptor					683:690	the insulin receptor	671:690	the insulin receptor	671:690	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	71	dep	kinases	661:667	arg1	receptor					725:732	insulin-like growth factor 1 receptor	696:732	insulin-like growth factor 1 receptor (IGF-1R)	696:741	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	71	dep	kinases	661:667	arg1	IGF-1R					735:740	IGF-1R	735:740	IGF-1R	735:740	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	71	dep	kinases	661:667	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	5	72	theme	Golgi-resident	946:959	arg1	convertase					972:981	Golgi-resident proprotein convertase	946:981	Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a)	946:1015	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	5	73	theme	convertase	972:981	arg1	5a					1005:1006	Golgi-resident proprotein convertase subtilisin/kexin type 5a	946:1006	Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a)	946:1015	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	5	73	theme	convertase	972:981	arg1	PCSK5a					1009:1014	PCSK5a	1009:1014	PCSK5a	1009:1014	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	3	74	dep	cells	425:429	arg1	STT3B					512:516	STT3B	512:516	STT3B	512:516	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	74	dep	cells	425:429	arg1	STT3A					502:506	STT3A	502:506	STT3A	502:506	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	74	dep	cells	425:429	arg1	cells					425:429	cells	425:429	cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B -	425:518	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	75	from	subunits	462:469	arg1	deficient					431:439	deficient	431:439	deficient	431:439	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	8	76	theme	CDG	1664:1666	arg1	pathogenesis					1668:1679	CDG pathogenesis	1664:1679	CDG pathogenesis	1664:1679	These results provide new insight into CDG pathogenesis and highlight how the surface abundance of some glycoproteins can be dually impacted by abnormal glycosylation.
31101650	6	77	gly	glycosylation	1154:1166	arg1	cells					1201:1205	cells	1201:1205	cells	1201:1205	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	6	77	gly	glycosylation	1154:1166	arg1	PCSK5a					1171:1176	PCSK5a	1171:1176	PCSK5a	1171:1176	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	6	77	gly	glycosylation	1154:1166	arg1	cells					1192:1196	STT3A-null cells	1181:1196	STT3A-null cells	1181:1196	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	3	78	dep	presence	535:542	arg1	the					531:533	the	531:533	the	531:533	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	3	79	theme	selective	389:397	arg1	labeling					413:420	selective exo-enzymatic labeling	389:420	selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B -	389:518	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	4	80	theme	N-linked	803:810	arg1	occupancy					824:832	decreased N-linked glycan site occupancy	793:832	decreased N-linked glycan site occupancy	793:832	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	1	81	from	occupancy	159:167	arg1	glycoproteins					172:184	glycoproteins	172:184	glycoproteins	172:184	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	7	82	from	inhibition	1472:1481	arg1	kinases					1530:1536	receptor tyrosine kinases	1512:1536	receptor tyrosine kinases	1512:1536	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	7	82	from	inhibition	1472:1481	arg1	convertases					1548:1558	their convertases	1542:1558	their convertases	1542:1558	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	4	83	theme	reduced	608:614	arg1	abundance					616:624	reduced abundance	608:624	reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface	608:763	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	84	theme	STT3A-null	768:777	arg1	cells					779:783	STT3A-null cells	768:783	STT3A-null cells	768:783	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	3	85	theme	oligosaccharyltransferase	474:498	arg1	subunits					462:469	the two catalytic subunits	444:469	the two catalytic subunits of oligosaccharyltransferase	444:498	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	0	86	theme	N-linked	24:31	arg1	glycosylation					33:45	N-linked glycosylation	24:45	N-linked glycosylation	24:45	Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.
31101650	5	87	theme	furin	1021:1025	arg1	cDNA					1027:1030	furin cDNA	1021:1030	furin cDNA to wild-type and mutant cells	1021:1060	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	3	88	theme	cells	425:429	arg1	labeling					413:420	selective exo-enzymatic labeling	389:420	selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B -	389:518	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31101650	8	89	theme	surface	1703:1709	arg1	abundance					1711:1719	the surface abundance	1699:1719	the surface abundance of some glycoproteins	1699:1741	These results provide new insight into CDG pathogenesis and highlight how the surface abundance of some glycoproteins can be dually impacted by abnormal glycosylation.
31101650	7	90	link	N-linked	1486:1493	arg1	glycosylation					1495:1507	N-linked glycosylation	1486:1507	N-linked glycosylation	1486:1507	Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization.
31101650	0	91	theme	tyrosine	64:71	arg1	kinase					73:78	receptor tyrosine kinase	55:78	receptor tyrosine kinase processing	55:89	Selective inhibition of N-linked glycosylation impairs receptor tyrosine kinase processing.
31101650	5	92	gly	under-glycosylated	1071:1088	arg1	PCSK5a					1099:1104	PCSK5a	1099:1104	PCSK5a	1099:1104	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	5	92	gly	under-glycosylated	1071:1088	arg1	forms					1090:1094	under-glycosylated forms	1071:1094	under-glycosylated forms of PCSK5a, but not furin,	1071:1120	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	5	92	gly	under-glycosylated	1071:1088	arg1	furin					1115:1119	furin	1115:1119	furin	1115:1119	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	8	93	theme	glycoproteins	1729:1741	arg1	abundance					1711:1719	the surface abundance	1699:1719	the surface abundance of some glycoproteins	1699:1741	These results provide new insight into CDG pathogenesis and highlight how the surface abundance of some glycoproteins can be dually impacted by abnormal glycosylation.
31101650	6	94	theme	STT3A-null	1181:1190	arg1	cells					1192:1196	STT3A-null cells	1181:1196	STT3A-null cells	1181:1196	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	1	95	theme	Global	92:97	arg1	inhibition					99:108	Global inhibition	92:108	Global inhibition of N-linked glycosylation	92:134	Global inhibition of N-linked glycosylation broadly reduces glycan occupancy on glycoproteins, but identifying how this inhibition functionally impacts specific glycoproteins is challenging.
31101650	4	96	theme	site	819:822	arg1	occupancy					824:832	decreased N-linked glycan site occupancy	793:832	decreased N-linked glycan site occupancy	793:832	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	6	97	from	glycosylation	1154:1166	arg1	cells					1201:1205	cells	1201:1205	cells	1201:1205	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	6	97	from	glycosylation	1154:1166	arg1	cells					1192:1196	STT3A-null cells	1181:1196	STT3A-null cells	1181:1196	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	5	98	theme	under-glycosylated	1071:1088	arg1	forms					1090:1094	under-glycosylated forms	1071:1094	under-glycosylated forms of PCSK5a, but not furin,	1071:1120	Providing cDNA for Golgi-resident proprotein convertase subtilisin/kexin type 5a (PCSK5a) and furin cDNA to wild-type and mutant cells produced under-glycosylated forms of PCSK5a, but not furin, in cells lacking STT3A.
31101650	6	99	theme	PCSK5a	1171:1176	arg1	glycosylation					1154:1166	Reduced glycosylation	1146:1166	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1	1146:1264	Reduced glycosylation of PCSK5a in STT3A-null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences.
31101650	4	100	theme	insulin	675:681	arg1	receptor					683:690	the insulin receptor	671:690	the insulin receptor	671:690	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	4	100	theme	insulin	675:681	arg1	kinases					661:667	two canonical tyrosine receptor kinases	629:667	two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) -	629:743	We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A-null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization.
31101650	3	101	theme	cell	572:575	arg1	glycoproteins					585:597	cell surface glycoproteins	572:597	cell surface glycoproteins	572:597	We used selective exo-enzymatic labeling of cells deficient in the two catalytic subunits of oligosaccharyltransferase - STT3A and STT3B - to monitor the presence and glycosylation status of cell surface glycoproteins.
31019513	2	0	theme	signaling	571:579	arg1	pathogens					502:510	pathogens	502:510	pathogens	502:510	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	0	theme	signaling	571:579	arg1	effects					543:549	the potential deleterious effects	517:549	the potential deleterious effects of dysregulated BCR signaling	517:579	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	0	theme	signaling	571:579	arg1	malignancies					600:611	B cell malignancies	593:611	B cell malignancies	593:611	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	0	theme	signaling	571:579	arg1	disease					627:633	autoimmune disease	616:633	autoimmune disease	616:633	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	3	1	from	co-receptors	659:670	arg1	cells					677:681	B cells	675:681	B cells	675:681	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	11	2	theme	altered	1821:1827	arg1	organization					1834:1845	altered CD22 organization	1821:1845	altered CD22 organization	1821:1845	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	9	3	theme	CD22	1604:1607	arg1	association					1617:1627	its association	1613:1627	its association with BCR	1613:1636	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	9	3	theme	CD22	1604:1607	arg1	organization					1588:1599	the nanoscale organization	1574:1599	the nanoscale organization of CD22	1574:1607	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	6	4	gly	glycosylation	1187:1199	arg2	sites					1201:1205	these glycosylation sites	1181:1205	these glycosylation sites	1181:1205	We were interested in how these glycosylation sites mediate homotypic vs. heterotypic interactions.
31019513	6	5	theme	heterotypic	1229:1239	arg1	interactions					1241:1252	homotypic vs. heterotypic interactions	1215:1252	homotypic vs. heterotypic interactions	1215:1252	We were interested in how these glycosylation sites mediate homotypic vs. heterotypic interactions.
31019513	11	6	theme	BCR	1971:1973	arg1	signaling					1975:1983	BCR signaling	1971:1983	BCR signaling	1971:1983	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	7	7	theme	acid	1371:1374	arg1	site					1384:1387	the sialic acid binding site	1360:1387	the sialic acid binding site	1360:1387	To this end, we mutated five out of the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site.
31019513	6	8	theme	homotypic	1215:1223	arg1	interactions					1241:1252	homotypic vs. heterotypic interactions	1215:1252	homotypic vs. heterotypic interactions	1215:1252	We were interested in how these glycosylation sites mediate homotypic vs. heterotypic interactions.
31019513	10	9	theme	glycosylation	1675:1687	arg1	sites					1689:1693	these five glycosylation sites	1664:1693	these five glycosylation sites	1664:1693	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	2	10	theme	cell	595:598	arg1	malignancies					600:611	B cell malignancies	593:611	B cell malignancies	593:611	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	11	theme	effects	543:549	arg1	clearance					489:497	the clearance	485:497	the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease	485:633	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	9	12	used	used	1471:1474	arg2	We					1468:1469	We	1468:1469	We	1468:1469	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	3	13	theme	binding	706:712	arg1	protein					714:720	a sialic-acid binding protein	692:720	a sialic-acid binding protein	692:720	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	3	13	theme	binding	706:712	arg1	CD22					686:689	CD22	686:689	CD22	686:689	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	10	14	theme	clustering	1709:1718	arg1	tendency					1720:1727	the clustering tendency	1705:1727	the clustering tendency of CD22	1705:1735	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	13	15	theme	CD22	2261:2264	arg1	organization					2232:2243	organization	2232:2243	organization	2232:2243	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	13	15	theme	CD22	2261:2264	arg1	function					2249:2256	function	2249:2256	function	2249:2256	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	2	16	theme	potential	521:529	arg1	effects					543:549	the potential deleterious effects	517:549	the potential deleterious effects of dysregulated BCR signaling	517:579	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	16	theme	potential	521:529	arg1	malignancies					600:611	B cell malignancies	593:611	B cell malignancies	593:611	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	16	theme	potential	521:529	arg1	disease					627:633	autoimmune disease	616:633	autoimmune disease	616:633	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	8	17	theme	Glycan	1390:1395	arg1	N101					1402:1405	Glycan site N101	1390:1405	Glycan site N101	1390:1405	Glycan site N101 was not mutated as this resulted in lack of CD22 expression.
31019513	6	18	theme	glycosylation	1187:1199	arg1	sites					1201:1205	these glycosylation sites	1181:1205	these glycosylation sites	1181:1205	We were interested in how these glycosylation sites mediate homotypic vs. heterotypic interactions.
31019513	12	19	theme	secreted	2061:2068	arg1	galectin-9					2078:2087	galectin-9	2078:2087	galectin-9	2078:2087	Importantly, we identified that these sites may be ligands for the soluble secreted lectin, galectin-9, and are necessary for galectin-9 mediated inhibition of BCR signaling.
31019513	12	19	theme	secreted	2061:2068	arg1	lectin					2070:2075	the soluble secreted lectin	2049:2075	the soluble secreted lectin	2049:2075	Importantly, we identified that these sites may be ligands for the soluble secreted lectin, galectin-9, and are necessary for galectin-9 mediated inhibition of BCR signaling.
31019513	7	20	link	N-linked	1299:1306	arg1	residues					1322:1329	the six N-linked glycosylation residues	1291:1329	the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site	1291:1387	To this end, we mutated five out of the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site.
31019513	4	21	theme	CD22	864:867	arg1	importance					850:859	the importance	846:859	the importance of CD22 in attenuating BCR signaling	846:896	Although the importance of CD22 in attenuating BCR signaling is well established, we still do not fully understand what mediates CD22 organization and association to BCRs.
31019513	11	22	theme	CD22	1900:1903	arg1	phosphorylation					1905:1919	CD22 phosphorylation	1900:1919	CD22 phosphorylation	1900:1919	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	2	23	theme	dysregulated	554:565	arg1	signaling					571:579	dysregulated BCR signaling	554:579	dysregulated BCR signaling	554:579	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	7	24	theme	N-linked	1299:1306	arg1	residues					1322:1329	the six N-linked glycosylation residues	1291:1329	the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site	1291:1387	To this end, we mutated five out of the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site.
31019513	3	25	gly	sialylated	764:773	arg1	molecules					780:788	other sialylated CD22 molecules	758:788	other sialylated CD22 molecules	758:788	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	3	26	theme	sialylated	764:773	arg1	molecules					780:788	other sialylated CD22 molecules	758:788	other sialylated CD22 molecules	758:788	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	10	27	theme	density	1760:1766	arg1	nanoclusters					1773:1784	higher density CD22 nanoclusters	1753:1784	higher density CD22 nanoclusters	1753:1784	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	13	28	theme	N-linked	2202:2209	arg1	glycosylation					2211:2223	N-linked glycosylation	2202:2223	N-linked glycosylation	2202:2223	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	5	29	from	function	1114:1121	arg1	domain					1102:1107	its extracellular domain	1084:1107	its extracellular domain	1084:1107	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	5	30	theme	N-linked	1052:1059	arg1	sites					1075:1079	12 N-linked glycosylation sites	1049:1079	12 N-linked glycosylation sites	1049:1079	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	9	31	theme	dual-color	1476:1485	arg1	imaging					1504:1510	dual-color super-resolution imaging	1476:1510	dual-color super-resolution imaging	1476:1510	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	2	32	theme	pathogens	502:510	arg1	clearance					489:497	the clearance	485:497	the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease	485:633	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	8	33	theme	CD22	1451:1454	arg1	expression					1456:1465	CD22 expression	1451:1465	CD22 expression	1451:1465	Glycan site N101 was not mutated as this resulted in lack of CD22 expression.
31019513	2	34	theme	autoimmune	616:625	arg1	disease					627:633	autoimmune disease	616:633	autoimmune disease	616:633	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	35	theme	B	406:406	arg1	receptor					413:420	B cell receptor	406:420	B cell receptor (BCR) signaling	406:436	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	35	theme	B	406:406	arg1	BCR					423:425	BCR	423:425	BCR	423:425	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	5	36	theme	sites	1075:1079	arg1	function					1114:1121	the function	1110:1121	the function	1110:1121	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	5	37	link	N-linked	1052:1059	arg1	sites					1075:1079	12 N-linked glycosylation sites	1049:1079	12 N-linked glycosylation sites	1049:1079	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	13	38	gly	glycosylation	2211:2223	arg1	organization					2232:2243	organization	2232:2243	organization	2232:2243	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	13	38	gly	glycosylation	2211:2223	arg1	function					2249:2256	function	2249:2256	function	2249:2256	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	12	39	theme	signaling	2150:2158	arg1	inhibition					2132:2141	galectin-9 mediated inhibition	2112:2141	galectin-9 mediated inhibition of BCR signaling	2112:2158	Importantly, we identified that these sites may be ligands for the soluble secreted lectin, galectin-9, and are necessary for galectin-9 mediated inhibition of BCR signaling.
31019513	0	40	theme	N-Linked	0:7	arg1	Glycosylation					9:21	N-Linked Glycosylation	0:21	N-Linked Glycosylation	0:21	N-Linked Glycosylation Regulates CD22 Organization and Function.
31019513	1	41	theme	cell	100:103	arg1	proteins					113:120	cell surface proteins	100:120	cell surface proteins	100:120	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	7	42	from	residues	1322:1329	arg1	CD22					1334:1337	CD22	1334:1337	CD22 localized closest to the sialic acid binding site	1334:1387	To this end, we mutated five out of the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site.
31019513	2	43	theme	signaling	428:436	arg1	importance					392:401	the importance	388:401	the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease	388:633	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	11	44	theme	BCR	1926:1928	arg1	stimulation					1930:1940	BCR stimulation	1926:1940	BCR stimulation	1926:1940	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	11	45	theme	N-glycan	1874:1881	arg1	sites					1883:1887	N-glycan sites	1874:1887	N-glycan sites	1874:1887	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	1	46	theme	proteins	113:120	arg1	clustering					86:95	clustering	86:95	clustering	86:95	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	1	46	theme	proteins	113:120	arg1	organization					69:80	organization	69:80	organization	69:80	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	12	47	theme	mediated	2123:2130	arg1	inhibition					2132:2141	galectin-9 mediated inhibition	2112:2141	galectin-9 mediated inhibition of BCR signaling	2112:2158	Importantly, we identified that these sites may be ligands for the soluble secreted lectin, galectin-9, and are necessary for galectin-9 mediated inhibition of BCR signaling.
31019513	2	48	theme	receptor	413:420	arg1	signaling					428:436	B cell receptor (BCR) signaling	406:436	B cell receptor (BCR) signaling	406:436	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	9	49	theme	altered	1541:1547	arg1	glycosylation					1549:1561	altered glycosylation	1541:1561	altered glycosylation of CD22	1541:1569	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	10	50	gly	glycosylation	1675:1687	arg2	five					1670:1673	five	1670:1673	five	1670:1673	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	10	50	gly	glycosylation	1675:1687	arg2	sites					1689:1693	these five glycosylation sites	1664:1693	these five glycosylation sites	1664:1693	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	3	51	theme	co-receptors	659:670	arg1	One					636:638	One	636:638	One	636:638	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	3	51	theme	co-receptors	659:670	arg1	co-receptors					659:670	main inhibitory co-receptors	643:670	main inhibitory co-receptors on B cells	643:681	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	2	52	theme	function	350:357	arg1	understanding					326:338	our understanding	322:338	our understanding of immune function in health and disease	322:379	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	3	53	theme	main	643:646	arg1	co-receptors					659:670	main inhibitory co-receptors	643:670	main inhibitory co-receptors on B cells	643:681	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	11	54	theme	CD22	1829:1832	arg1	organization					1834:1845	altered CD22 organization	1821:1845	altered CD22 organization	1821:1845	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	9	55	theme	nanoscale	1578:1586	arg1	organization					1588:1599	the nanoscale organization	1574:1599	the nanoscale organization of CD22	1574:1607	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	9	56	gly	glycosylation	1549:1561	arg1	CD22					1566:1569	CD22	1566:1569	CD22	1566:1569	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	9	57	with	organization	1588:1599	arg1	BCR					1634:1636	BCR	1634:1636	BCR	1634:1636	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	2	58	from	function	350:357	arg1	disease					373:379	disease	373:379	disease	373:379	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	58	from	function	350:357	arg1	health					362:367	health	362:367	health	362:367	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	3	59	theme	B	675:675	arg1	cells					677:681	B cells	675:681	B cells	675:681	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	2	60	from	health	362:367	arg1	understanding					326:338	our understanding	322:338	our understanding of immune function in health and disease	322:379	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	3	61	theme	sialic-acid	694:704	arg1	protein					714:720	a sialic-acid binding protein	692:720	a sialic-acid binding protein	692:720	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	3	61	theme	sialic-acid	694:704	arg1	CD22					686:689	CD22	686:689	CD22	686:689	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	11	62	with	Consistent	1787:1796	arg1	findings					1809:1816	these findings	1803:1816	these findings of altered CD22 organization	1803:1845	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	10	63	theme	sites	1689:1693	arg1	mutation					1652:1659	mutation	1652:1659	mutation of these five glycosylation sites	1652:1693	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	2	64	theme	B	451:451	arg1	cells					453:457	B cells	451:457	B cells	451:457	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	65	from	disease	373:379	arg1	understanding					326:338	our understanding	322:338	our understanding of immune function in health and disease	322:379	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	7	66	theme	binding	1376:1382	arg1	site					1384:1387	the sialic acid binding site	1360:1387	the sialic acid binding site	1360:1387	To this end, we mutated five out of the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site.
31019513	10	67	theme	CD22	1732:1735	arg1	tendency					1720:1727	the clustering tendency	1705:1727	the clustering tendency of CD22	1705:1735	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	13	68	theme	heterotypic	2293:2303	arg1	interactions					2305:2316	heterotypic interactions	2293:2316	heterotypic interactions between CD22 and its binding partners	2293:2354	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	2	69	theme	B	593:593	arg1	malignancies					600:611	B cell malignancies	593:611	B cell malignancies	593:611	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	7	70	theme	sialic	1364:1369	arg1	site					1384:1387	the sialic acid binding site	1360:1387	the sialic acid binding site	1360:1387	To this end, we mutated five out of the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site.
31019513	5	71	gly	glycosylation	1061:1073	arg2	12					1049:1050	12	1049:1050	12	1049:1050	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	5	71	gly	glycosylation	1061:1073	arg2	sites					1075:1079	12 N-linked glycosylation sites	1049:1079	12 N-linked glycosylation sites	1049:1079	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	1	72	theme	biophysical	192:202	arg1	mechanisms					204:213	the biophysical mechanisms	188:213	the biophysical mechanisms regulating these parameters	188:241	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	4	73	theme	BCR	884:886	arg1	signaling					888:896	BCR signaling	884:896	BCR signaling	884:896	Although the importance of CD22 in attenuating BCR signaling is well established, we still do not fully understand what mediates CD22 organization and association to BCRs.
31019513	8	74	theme	site	1397:1400	arg1	N101					1402:1405	Glycan site N101	1390:1405	Glycan site N101	1390:1405	Glycan site N101 was not mutated as this resulted in lack of CD22 expression.
31019513	10	75	theme	higher	1753:1758	arg1	nanoclusters					1773:1784	higher density CD22 nanoclusters	1753:1784	higher density CD22 nanoclusters	1753:1784	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	12	76	theme	soluble	2053:2059	arg1	galectin-9					2078:2087	galectin-9	2078:2087	galectin-9	2078:2087	Importantly, we identified that these sites may be ligands for the soluble secreted lectin, galectin-9, and are necessary for galectin-9 mediated inhibition of BCR signaling.
31019513	12	76	theme	soluble	2053:2059	arg1	lectin					2070:2075	the soluble secreted lectin	2049:2075	the soluble secreted lectin	2049:2075	Importantly, we identified that these sites may be ligands for the soluble secreted lectin, galectin-9, and are necessary for galectin-9 mediated inhibition of BCR signaling.
31019513	3	77	theme	other	758:762	arg1	molecules					780:788	other sialylated CD22 molecules	758:788	other sialylated CD22 molecules	758:788	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	2	78	theme	BCR	567:569	arg1	signaling					571:579	dysregulated BCR signaling	554:579	dysregulated BCR signaling	554:579	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	1	79	theme	critical	130:137	arg1	role					139:142	a critical role	128:142	a critical role	128:142	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	9	80	from	impact	1531:1536	arg1	association					1617:1627	its association	1613:1627	its association with BCR	1613:1636	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	9	80	from	impact	1531:1536	arg1	organization					1588:1599	the nanoscale organization	1574:1599	the nanoscale organization of CD22	1574:1607	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	7	81	theme	glycosylation	1308:1320	arg1	residues					1322:1329	the six N-linked glycosylation residues	1291:1329	the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site	1291:1387	To this end, we mutated five out of the six N-linked glycosylation residues on CD22 localized closest to the sialic acid binding site.
31019513	1	82	dep	organization	69:80	arg1	The					65:67	The	65:67	The	65:67	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	10	83	theme	CD22	1768:1771	arg1	nanoclusters					1773:1784	higher density CD22 nanoclusters	1753:1784	higher density CD22 nanoclusters	1753:1784	We show that mutation of these five glycosylation sites increased the clustering tendency of CD22 and resulted in higher density CD22 nanoclusters.
31019513	3	84	theme	CD22	775:778	arg1	molecules					780:788	other sialylated CD22 molecules	758:788	other sialylated CD22 molecules	758:788	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	5	85	theme	extracellular	1088:1100	arg1	domain					1102:1107	its extracellular domain	1084:1107	its extracellular domain	1084:1107	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	1	86	theme	receptor	159:166	arg1	signaling					168:176	receptor signaling	159:176	receptor signaling	159:176	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	2	87	theme	deleterious	531:541	arg1	effects					543:549	the potential deleterious effects	517:549	the potential deleterious effects of dysregulated BCR signaling	517:579	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	87	theme	deleterious	531:541	arg1	malignancies					600:611	B cell malignancies	593:611	B cell malignancies	593:611	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	87	theme	deleterious	531:541	arg1	disease					627:633	autoimmune disease	616:633	autoimmune disease	616:633	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	88	from	understanding	326:338	arg1	disease					373:379	disease	373:379	disease	373:379	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	88	from	understanding	326:338	arg1	health					362:367	health	362:367	health	362:367	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	8	89	theme	expression	1456:1465	arg1	lack					1443:1446	lack	1443:1446	lack of CD22 expression	1443:1465	Glycan site N101 was not mutated as this resulted in lack of CD22 expression.
31019513	2	90	theme	immune	343:348	arg1	function					350:357	immune function	343:357	immune function in health and disease	343:379	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	5	91	theme	glycosylation	1061:1073	arg1	sites					1075:1079	12 N-linked glycosylation sites	1049:1079	12 N-linked glycosylation sites	1049:1079	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	9	92	theme	super-resolution	1487:1502	arg1	imaging					1504:1510	dual-color super-resolution imaging	1476:1510	dual-color super-resolution imaging	1476:1510	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	5	93	from	sites	1075:1079	arg1	domain					1102:1107	its extracellular domain	1084:1107	its extracellular domain	1084:1107	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	12	94	theme	BCR	2146:2148	arg1	signaling					2150:2158	BCR signaling	2146:2158	BCR signaling	2146:2158	Importantly, we identified that these sites may be ligands for the soluble secreted lectin, galectin-9, and are necessary for galectin-9 mediated inhibition of BCR signaling.
31019513	0	95	theme	CD22	33:36	arg1	Organization					38:49	CD22 Organization	33:49	CD22 Organization	33:49	N-Linked Glycosylation Regulates CD22 Organization and Function.
31019513	1	96	theme	surface	105:111	arg1	proteins					113:120	cell surface proteins	100:120	cell surface proteins	100:120	The organization and clustering of cell surface proteins plays a critical role in controlling receptor signaling; however, the biophysical mechanisms regulating these parameters are not well understood.
31019513	11	97	theme	sites	1883:1887	arg1	mutation					1862:1869	mutation	1862:1869	mutation of N-glycan sites	1862:1887	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
31019513	5	98	from	domain	1102:1107	arg1	function					1114:1121	the function	1110:1121	the function	1110:1121	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	13	99	theme	binding	2339:2345	arg1	partners					2347:2354	its binding partners	2335:2354	its binding partners	2335:2354	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	13	100	link	N-linked	2202:2209	arg1	glycosylation					2211:2223	N-linked glycosylation	2202:2223	N-linked glycosylation	2202:2223	Taken together, these findings implicate N-linked glycosylation in the organization and function of CD22, likely through regulating heterotypic interactions between CD22 and its binding partners.
31019513	2	101	theme	cell	408:411	arg1	receptor					413:420	B cell receptor	406:420	B cell receptor (BCR) signaling	406:436	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	2	101	theme	cell	408:411	arg1	BCR					423:425	BCR	423:425	BCR	423:425	Elucidating these mechanisms is highly significant to our understanding of immune function in health and disease, given the importance of B cell receptor (BCR) signaling in directing B cells to produce antibodies for the clearance of pathogens, and the potential deleterious effects of dysregulated BCR signaling, such as in B cell malignancies or autoimmune disease.
31019513	9	102	theme	glycosylation	1549:1561	arg1	impact					1531:1536	the impact	1527:1536	the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR	1527:1636	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	4	103	theme	CD22	966:969	arg1	organization					971:982	CD22 organization	966:982	CD22 organization	966:982	Although the importance of CD22 in attenuating BCR signaling is well established, we still do not fully understand what mediates CD22 organization and association to BCRs.
31019513	3	104	theme	inhibitory	648:657	arg1	co-receptors					659:670	main inhibitory co-receptors	643:670	main inhibitory co-receptors on B cells	643:681	One of main inhibitory co-receptors on B cells is CD22, a sialic-acid binding protein, which interacts homotypically with other sialylated CD22 molecules, as well as heterotypically with IgM and CD45.
31019513	9	105	theme	CD22	1566:1569	arg1	glycosylation					1549:1561	altered glycosylation	1541:1561	altered glycosylation of CD22	1541:1569	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	5	106	gly	glycosylated	1024:1035	arg1	CD22					1009:1012	CD22	1009:1012	CD22	1009:1012	CD22 is highly glycosylated, containing 12 N-linked glycosylation sites on its extracellular domain, the function of which remain to be resolved.
31019513	9	107	with	association	1617:1627	arg1	BCR					1634:1636	BCR	1634:1636	BCR	1634:1636	We used dual-color super-resolution imaging to investigate the impact of altered glycosylation of CD22 on the nanoscale organization of CD22 and its association with BCR.
31019513	11	108	theme	organization	1834:1845	arg1	findings					1809:1816	these findings	1803:1816	these findings of altered CD22 organization	1803:1845	Consistent with these findings of altered CD22 organization, we found that mutation of N-glycan sites attenuated CD22 phosphorylation upon BCR stimulation, and consequently, increased BCR signaling.
30224358	8	0	from	combination	1452:1462	arg1	disruption					1394:1403	disruption	1394:1403	disruption of both proposed activation mechanisms even in combination	1394:1462	In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis.
30224358	2	1	theme	HCF-1PRO	397:404	arg1	repeat					406:411	a single known substrate-the so-called HCF-1PRO repeat	358:411	a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1)	358:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	4	2	theme	extended	635:642	arg1	region					659:664	an important extended threonine-rich region	622:664	an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region	622:735	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	2	3	theme	so-called	387:395	arg1	repeat					406:411	a single known substrate-the so-called HCF-1PRO repeat	358:411	a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1)	358:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	4	4	theme	important	625:633	arg1	region					659:664	an important extended threonine-rich region	622:664	an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region	622:735	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	7	5	theme	activation	1291:1300	arg1	mechanisms					1302:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	2	6	theme	transient	315:323	arg1	glycosylation					335:347	a transient glutamate glycosylation	313:347	a transient glutamate glycosylation	313:347	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	6	7	theme	glutamate	1131:1139	arg1	residue					1141:1147	an appropriately positioned glutamate residue	1103:1147	an appropriately positioned glutamate residue	1103:1147	Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue.
30224358	0	8	theme	UDP-GlcNAc	85:94	arg1	glycosylation					96:108	UDP-GlcNAc glycosylation	85:108	UDP-GlcNAc glycosylation	85:108	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	5	9	with	glycosylation	875:887	arg1	phosphorothioate					943:958	the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	894:994	phosphorothioate	943:958	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	5	9	with	glycosylation	875:887	arg1	co-substrates					982:994	the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	894:994	co-substrates	982:994	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	4	10	theme	threonine-rich	644:657	arg1	region					659:664	an important extended threonine-rich region	622:664	an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region	622:735	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	0	11	theme	proteolysis	114:124	arg1	activities					126:135	proteolysis activities	114:135	proteolysis activities	114:135	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	3	12	theme	distinct	524:531	arg1	glycosylation					533:545	these distinct glycosylation and proteolytic activities	518:572	glycosylation	533:545	Here, we probed the relationship between these distinct glycosylation and proteolytic activities.
30224358	7	13	theme	serine-acceptor	1267:1281	arg1	mechanisms					1302:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	5	14	theme	diastereomer	930:941	arg1	phosphorothioate					943:958	the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	894:994	phosphorothioate	943:958	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	9	15	theme	alternative	1630:1640	arg1	strategies					1663:1672	alternative molecular regulatory strategies	1630:1672	alternative molecular regulatory strategies	1630:1672	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	2	16	theme	transcriptional	420:434	arg1	factor					459:464	the transcriptional co-regulator host-cell factor 1	416:466	the transcriptional co-regulator host-cell factor 1 (HCF-1)	416:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	2	16	theme	transcriptional	420:434	arg1	HCF-1					469:473	HCF-1	469:473	HCF-1	469:473	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	2	17	theme	host-cell	449:457	arg1	factor					459:464	the transcriptional co-regulator host-cell factor 1	416:466	the transcriptional co-regulator host-cell factor 1 (HCF-1)	416:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	2	17	theme	host-cell	449:457	arg1	HCF-1					469:473	HCF-1	469:473	HCF-1	469:473	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	6	18	theme	positioned	1120:1129	arg1	residue					1141:1147	an appropriately positioned glutamate residue	1103:1147	an appropriately positioned glutamate residue	1103:1147	Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue.
30224358	7	19	theme	residue	1283:1289	arg1	mechanisms					1302:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	2	20	theme	co-regulator	436:447	arg1	factor					459:464	the transcriptional co-regulator host-cell factor 1	416:466	the transcriptional co-regulator host-cell factor 1 (HCF-1)	416:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	2	20	theme	co-regulator	436:447	arg1	HCF-1					469:473	HCF-1	469:473	HCF-1	469:473	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	0	21	theme	conserved	4:12	arg1	region					29:34	The conserved threonine-rich region	0:34	The conserved threonine-rich region of the HCF-1PRO repeat	0:57	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	8	22	from	disruption	1394:1403	arg1	combination					1452:1462	combination	1452:1462	combination	1452:1462	In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis.
30224358	5	23	theme	heterologous	811:822	arg1	sequences					834:842	heterologous substrate sequences	811:842	heterologous substrate sequences	811:842	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	4	24	contain	possesses	612:620	arg1	repeat					605:610	the HCF-1PRO repeat	592:610	the HCF-1PRO repeat	592:610	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	4	24	contain	possesses	612:620	arg2	region					659:664	an important extended threonine-rich region	622:664	an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region	622:735	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	1	25	theme	glycosyltransferase-protease	187:214	arg1	activities					216:225	dual glycosyltransferase-protease activities	182:225	dual glycosyltransferase-protease activities	182:225	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	9	26	theme	OGT	1545:1547	arg1	some					1575:1578	some	1575:1578	some	1575:1578	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	9	26	theme	OGT	1545:1547	arg1	strategies					1563:1572	OGT glycosylation strategies	1545:1572	OGT glycosylation strategies	1545:1572	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	7	27	theme	UDP-GlcNAc-based	1250:1265	arg1	mechanisms					1302:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	5	28	theme	UDP-5S-GlcNAc	964:976	arg1	co-substrates					982:994	the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	894:994	co-substrates	982:994	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	0	29	dep	OGT	81:83	arg1	glycosylation					96:108	UDP-GlcNAc glycosylation	85:108	UDP-GlcNAc glycosylation	85:108	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	0	29	dep	OGT	81:83	arg1	activities					126:135	proteolysis activities	114:135	proteolysis activities	114:135	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	4	30	theme	HCF-1PRO	596:603	arg1	repeat					605:610	the HCF-1PRO repeat	592:610	the HCF-1PRO repeat	592:610	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	7	31	theme	proposed	1228:1235	arg1	mechanisms					1302:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	9	32	theme	molecular	1642:1650	arg1	strategies					1663:1672	alternative molecular regulatory strategies	1630:1672	alternative molecular regulatory strategies	1630:1672	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	5	33	theme	serine	868:873	arg1	glycosylation					875:887	robust serine glycosylation	861:887	robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	861:994	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	9	34	theme	strategies	1663:1672	arg1	targets					1619:1625	targets	1619:1625	targets of alternative molecular regulatory strategies	1619:1672	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	5	35	theme	Rp-αS-UDP-GlcNAc	913:928	arg1	phosphorothioate					943:958	the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	894:994	phosphorothioate	943:958	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	0	36	theme	threonine-rich	14:27	arg1	region					29:34	The conserved threonine-rich region	0:34	The conserved threonine-rich region of the HCF-1PRO repeat	0:57	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	9	37	theme	glycosylation	1549:1561	arg1	some					1575:1578	some	1575:1578	some	1575:1578	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	9	37	theme	glycosylation	1549:1561	arg1	strategies					1563:1572	OGT glycosylation strategies	1545:1572	OGT glycosylation strategies	1545:1572	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	7	38	theme	OGT-based	1237:1245	arg1	mechanisms					1302:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms	1228:1311	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	2	39	theme	glutamate	325:333	arg1	glycosylation					335:347	a transient glutamate glycosylation	313:347	a transient glutamate glycosylation	313:347	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	2	40	dep	glycosylates	247:258	arg1	cleaves					350:356	cleaves	350:356	cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1)	350:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	8	41	theme	OGT-mediated	1480:1491	arg1	proteolysis					1493:1503	OGT-mediated proteolysis	1480:1503	OGT-mediated proteolysis	1480:1503	In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis.
30224358	4	42	theme	tetratricopeptide-repeat	699:722	arg1	region					730:735	the OGT tetratricopeptide-repeat (TPR) region	691:735	the OGT tetratricopeptide-repeat (TPR) region	691:735	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	4	43	theme	TPR	725:727	arg1	region					730:735	the OGT tetratricopeptide-repeat (TPR) region	691:735	the OGT tetratricopeptide-repeat (TPR) region	691:735	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	5	44	theme	OGT	978:980	arg1	co-substrates					982:994	the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	894:994	co-substrates	982:994	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	5	45	theme	HCF-1PRO-repeat	769:783	arg1	region					801:806	this HCF-1PRO-repeat, threonine-rich region	764:806	this HCF-1PRO-repeat, threonine-rich region	764:806	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	6	46	contain	contained	1093:1101	arg1	it					1090:1091	it	1090:1091	it	1090:1091	Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue.
30224358	6	46	contain	contained	1093:1101	arg2	residue					1141:1147	an appropriately positioned glutamate residue	1103:1147	an appropriately positioned glutamate residue	1103:1147	Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue.
30224358	2	47	theme	factor	459:464	arg1	repeat					406:411	a single known substrate-the so-called HCF-1PRO repeat	358:411	a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1)	358:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	0	48	theme	repeat	52:57	arg1	region					29:34	The conserved threonine-rich region	0:34	The conserved threonine-rich region of the HCF-1PRO repeat	0:57	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	9	49	theme	regulatory	1652:1661	arg1	strategies					1663:1672	alternative molecular regulatory strategies	1630:1672	alternative molecular regulatory strategies	1630:1672	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	5	50	theme	poor	908:911	arg1	phosphorothioate					943:958	the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	894:994	phosphorothioate	943:958	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	1	51	contain	possesses	172:180	arg1	OGT					167:169	OGT	167:169	OGT	167:169	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	1	51	contain	possesses	172:180	arg2	activities					216:225	dual glycosyltransferase-protease activities	182:225	dual glycosyltransferase-protease activities	182:225	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	1	51	contain	possesses	172:180	arg1	transferase					154:164	O-Linked GlcNAc transferase	138:164	O-Linked GlcNAc transferase (OGT)	138:170	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	7	52	theme	glutamate-containing	1167:1186	arg1	sequences					1204:1212	serine- or glutamate-containing HCF-1PRO-repeat sequences	1156:1212	serine- or glutamate-containing HCF-1PRO-repeat sequences	1156:1212	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	2	53	theme	substrate-the	373:385	arg1	repeat					406:411	a single known substrate-the so-called HCF-1PRO repeat	358:411	a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1)	358:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	0	54	theme	HCF-1PRO	43:50	arg1	repeat					52:57	the HCF-1PRO repeat	39:57	the HCF-1PRO repeat	39:57	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	6	55	theme	sequence	1071:1078	arg1	proteolysis					1025:1035	proteolysis	1025:1035	proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue	1025:1147	Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue.
30224358	3	56	theme	proteolytic	551:561	arg1	activities					563:572	these distinct glycosylation and proteolytic activities	518:572	activities	563:572	Here, we probed the relationship between these distinct glycosylation and proteolytic activities.
30224358	2	57	theme	known	367:371	arg1	repeat					406:411	a single known substrate-the so-called HCF-1PRO repeat	358:411	a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1)	358:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	6	58	theme	cleavage	1062:1069	arg1	sequence					1071:1078	a non-HCF-1PRO-repeat cleavage sequence	1040:1078	a non-HCF-1PRO-repeat cleavage sequence	1040:1078	Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue.
30224358	7	59	theme	HCF-1PRO-repeat	1188:1202	arg1	sequences					1204:1212	serine- or glutamate-containing HCF-1PRO-repeat sequences	1156:1212	serine- or glutamate-containing HCF-1PRO-repeat sequences	1156:1212	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	9	60	theme	strategies	1563:1572	arg1	multiplicity					1529:1540	a multiplicity	1527:1540	a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies	1527:1672	These results reveal a multiplicity of OGT glycosylation strategies, some leading to proteolysis, which could be targets of alternative molecular regulatory strategies.
30224358	5	61	theme	substrate	824:832	arg1	sequences					834:842	heterologous substrate sequences	811:842	heterologous substrate sequences	811:842	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	1	62	theme	O-Linked	138:145	arg1	OGT					167:169	OGT	167:169	OGT	167:169	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	1	62	theme	O-Linked	138:145	arg1	transferase					154:164	O-Linked GlcNAc transferase	138:164	O-Linked GlcNAc transferase (OGT)	138:170	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	8	63	from	mechanisms	1433:1442	arg1	combination					1452:1462	combination	1452:1462	combination	1452:1462	In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis.
30224358	5	64	theme	region	801:806	arg1	linkage					753:759	linkage	753:759	linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences	753:842	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	7	65	theme	serine-	1156:1162	arg1	sequences					1204:1212	serine- or glutamate-containing HCF-1PRO-repeat sequences	1156:1212	serine- or glutamate-containing HCF-1PRO-repeat sequences	1156:1212	Using serine- or glutamate-containing HCF-1PRO-repeat sequences, we show that proposed OGT-based or UDP-GlcNAc-based serine-acceptor residue activation mechanisms can be circumvented independently, but not when disrupted together.
30224358	8	66	theme	activation	1422:1431	arg1	mechanisms					1433:1442	both proposed activation mechanisms	1408:1442	both proposed activation mechanisms even in combination	1408:1462	In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis.
30224358	2	67	theme	proteins	295:302	arg1	threonines					272:281	threonines	272:281	threonines	272:281	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	2	67	theme	proteins	295:302	arg1	serines					260:266	serines	260:266	serines	260:266	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	1	68	theme	GlcNAc	147:152	arg1	OGT					167:169	OGT	167:169	OGT	167:169	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	1	68	theme	GlcNAc	147:152	arg1	transferase					154:164	O-Linked GlcNAc transferase	138:164	O-Linked GlcNAc transferase (OGT)	138:170	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	8	69	theme	proposed	1413:1420	arg1	mechanisms					1433:1442	both proposed activation mechanisms	1408:1442	both proposed activation mechanisms even in combination	1408:1462	In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis.
30224358	2	70	theme	single	360:365	arg1	repeat					406:411	a single known substrate-the so-called HCF-1PRO repeat	358:411	a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1)	358:474	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	0	71	theme	promiscuous	69:79	arg1	OGT					81:83	promiscuous OGT	69:83	promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities	69:135	The conserved threonine-rich region of the HCF-1PRO repeat activates promiscuous OGT:UDP-GlcNAc glycosylation and proteolysis activities.
30224358	4	72	theme	OGT	695:697	arg1	region					730:735	the OGT tetratricopeptide-repeat (TPR) region	691:735	the OGT tetratricopeptide-repeat (TPR) region	691:735	For proteolysis, the HCF-1PRO repeat possesses an important extended threonine-rich region that is tightly bound by the OGT tetratricopeptide-repeat (TPR) region.
30224358	2	73	theme	numerous	286:293	arg1	proteins					295:302	numerous proteins	286:302	numerous proteins	286:302	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	1	74	theme	dual	182:185	arg1	activities					216:225	dual glycosyltransferase-protease activities	182:225	dual glycosyltransferase-protease activities	182:225	O-Linked GlcNAc transferase (OGT) possesses dual glycosyltransferase-protease activities.
30224358	2	75	gly	glycosylates	247:258	arg1	threonines					272:281	threonines	272:281	threonines	272:281	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	2	75	gly	glycosylates	247:258	arg1	serines					260:266	serines	260:266	serines	260:266	OGT thereby stably glycosylates serines and threonines of numerous proteins and, via a transient glutamate glycosylation, cleaves a single known substrate-the so-called HCF-1PRO repeat of the transcriptional co-regulator host-cell factor 1 (HCF-1).
30224358	6	76	theme	non-HCF-1PRO-repeat	1042:1060	arg1	sequence					1071:1078	a non-HCF-1PRO-repeat cleavage sequence	1040:1078	a non-HCF-1PRO-repeat cleavage sequence	1040:1078	Furthermore, it potentiated proteolysis of a non-HCF-1PRO-repeat cleavage sequence, provided it contained an appropriately positioned glutamate residue.
30224358	5	77	theme	robust	861:866	arg1	glycosylation					875:887	robust serine glycosylation	861:887	robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates	861:994	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30224358	8	78	theme	mechanisms	1433:1442	arg1	disruption					1394:1403	disruption	1394:1403	disruption of both proposed activation mechanisms even in combination	1394:1462	In contrast, disruption of both proposed activation mechanisms even in combination did not inhibit OGT-mediated proteolysis.
30224358	5	79	dep	HCF-1PRO-repeat	769:783	arg1	threonine-rich					786:799	threonine-rich	786:799	threonine-rich	786:799	We report that linkage of this HCF-1PRO-repeat, threonine-rich region to heterologous substrate sequences also potentiates robust serine glycosylation with the otherwise poor Rp-αS-UDP-GlcNAc diastereomer phosphorothioate and UDP-5S-GlcNAc OGT co-substrates.
30786927	4	0	theme	bacterial	534:542	arg1	genomes					544:550	12 key bacterial genomes	527:550	12 key bacterial genomes from different phases of bloom	527:581	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	14	1	theme	global	2402:2407	arg1	changes					2425:2431	global warming-related changes	2402:2431	global warming-related changes in carbon remineralization	2402:2458	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	11	2	from	dominant	1743:1750	arg1	phases					1759:1764	all phases	1755:1764	all phases of the polynya bloom	1755:1785	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	8	3	dep	Gammaproteobacteria	1171:1189	arg1	SAR92					1211:1215	SAR92	1211:1215	SAR92	1211:1215	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	8	3	dep	Gammaproteobacteria	1171:1189	arg1	Ant4D3					1192:1197	Ant4D3	1192:1197	Ant4D3	1192:1197	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	8	3	dep	Gammaproteobacteria	1171:1189	arg1	SUP05					1200:1204	SUP05	1200:1204	SUP05	1200:1204	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	2	4	theme	trophic	286:292	arg1	levels					294:299	higher trophic levels	279:299	higher trophic levels	279:299	Carbon fixed by phytoplankton in the water column is transferred to higher trophic levels, and finally, to the deep ocean.
30786927	4	5	theme	genes	614:618	arg1	expression					600:609	the expression	596:609	the expression of genes involved in organic carbon remineralization	596:662	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	3	6	theme	heterotrophic	478:490	arg1	activity					492:499	high bacterial heterotrophic activity	463:499	high bacterial heterotrophic activity	463:499	However, in the Amundsen Sea, most of this organic carbon does not reach the sediment but is degraded in the water column due to high bacterial heterotrophic activity.
30786927	9	7	attach	predominant	1500:1510	arg1	ocean					1548:1552	the sea ice-covered oligotrophic ocean	1515:1552	the sea ice-covered oligotrophic ocean	1515:1552	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	9	7	attach	predominant	1500:1510	arg2	clade					1478:1482	the SAR11 clade	1468:1482	the SAR11 clade	1468:1482	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	9	7	attach	predominant	1500:1510	arg2	predominant					1500:1510	predominant	1500:1510	predominant	1500:1510	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	10	8	theme	peak	1701:1704	arg1	phases					1718:1723	the peak and decline phases	1697:1723	the peak and decline phases	1697:1723	SAR92 clade showed transcriptional activity for utilization of both polysaccharides and LMW-DOM; this may account for their abundance both in the peak and decline phases.
30786927	1	9	theme	Phaeocystis	187:197	arg1	antarctica					199:208	Phaeocystis antarctica	187:208	Phaeocystis antarctica	187:208	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	12	10	theme	Genomic	1899:1905	arg1	reconstruction					1907:1920	CONCLUSIONS Genomic reconstruction	1887:1920	CONCLUSIONS Genomic reconstruction	1887:1920	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	9	11	from	abundance	1413:1421	arg1	waters					1454:1459	organic carbon-rich polynya waters	1426:1459	organic carbon-rich polynya waters	1426:1459	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	14	12	from	antarctica	2299:2308	arg1	phytoplankton					2277:2289	phytoplankton	2277:2289	phytoplankton from P. antarctica to diatoms	2277:2319	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	14	12	from	antarctica	2299:2308	arg1	changes					2266:2272	compositional changes	2252:2272	compositional changes in phytoplankton from P. antarctica to diatoms	2252:2319	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	12	13	theme	Antarctic	2027:2035	arg1	polynya					2037:2043	the Antarctic polynya	2023:2043	the Antarctic polynya	2023:2043	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	5	14	theme	high	667:670	arg1	correlation					672:682	A high correlation	665:682	A high correlation of gene expression between the peak and decline phases	665:737	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	5	15	dep	peak	715:718	arg1	the					711:713	the	711:713	the	711:713	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	5	15	dep	peak	715:718	arg1	phases					732:737	phases	732:737	phases	732:737	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	7	16	theme	Polaribacter	998:1009	arg1	bins					1011:1014	Two dominant Polaribacter bins	985:1014	Two dominant Polaribacter bins	985:1014	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	11	17	theme	Antarctic	1867:1875	arg1	polynyas					1877:1884	the Antarctic polynyas	1863:1884	the Antarctic polynyas	1863:1884	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	5	18	theme	expression	814:823	arg1	comparison					795:804	an individual genome bin-based pairwise comparison	755:804	an individual genome bin-based pairwise comparison of gene expression	755:823	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	12	19	theme	dominant	2002:2009	arg1	bacteria					2011:2018	dominant bacteria	2002:2018	dominant bacteria	2002:2018	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	10	20	theme	decline	1710:1716	arg1	phases					1718:1723	the peak and decline phases	1697:1723	the peak and decline phases	1697:1723	SAR92 clade showed transcriptional activity for utilization of both polysaccharides and LMW-DOM; this may account for their abundance both in the peak and decline phases.
30786927	6	21	theme	peak	898:901	arg1	phase					903:907	the peak phase	894:907	the peak phase	894:907	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	13	22	theme	substrates	2172:2181	arg1	availability					2156:2167	the availability	2152:2167	the availability of substrates derived from the P. antarctica bloom	2152:2218	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	9	23	theme	organic	1426:1432	arg1	waters					1454:1459	organic carbon-rich polynya waters	1426:1459	organic carbon-rich polynya waters	1426:1459	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	6	24	theme	total	966:970	arg1	mRNA					972:975	the total mRNA reads	962:981	the total mRNA reads	962:981	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	4	25	theme	carbon	640:645	arg1	remineralization					647:662	organic carbon remineralization	632:662	organic carbon remineralization	632:662	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	5	26	theme	pairwise	786:793	arg1	comparison					795:804	an individual genome bin-based pairwise comparison	755:804	an individual genome bin-based pairwise comparison of gene expression	755:823	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	9	27	theme	polynya	1446:1452	arg1	waters					1454:1459	organic carbon-rich polynya waters	1426:1459	organic carbon-rich polynya waters	1426:1459	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	6	28	dep	high	947:950	arg1	%					957:957	48.9%	953:957	48.9% of the total mRNA reads	953:981	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	6	28	dep	high	947:950	arg1	mRNA					972:975	the total mRNA reads	962:981	the total mRNA reads	962:981	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	1	29	theme	production	165:174	arg1	Polynyas					103:110	BACKGROUND Polynyas	92:110	BACKGROUND Polynyas in the Southern Ocean	92:132	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	1	29	theme	production	165:174	arg1	regions					138:144	regions	138:144	regions of intense primary production	138:174	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	14	30	theme	Global	2221:2226	arg1	warming					2228:2234	Global warming	2221:2234	Global warming	2221:2234	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	5	31	theme	expression	692:701	arg1	correlation					672:682	A high correlation	665:682	A high correlation of gene expression between the peak and decline phases	665:737	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	9	32	from	ocean	1548:1552	arg1	predominant					1500:1510	predominant	1500:1510	predominant	1500:1510	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	9	32	from	ocean	1548:1552	arg1	clade					1478:1482	the SAR11 clade	1468:1482	the SAR11 clade	1468:1482	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	8	33	theme	molecular	1253:1261	arg1	LMW-DOM					1296:1302	LMW-DOM	1296:1302	LMW-DOM	1296:1302	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	8	33	theme	molecular	1253:1261	arg1	matter					1288:1293	low molecular weight-dissolved organic matter	1249:1293	low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes	1249:1332	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	10	34	theme	transcriptional	1574:1588	arg1	activity					1590:1597	transcriptional activity	1574:1597	transcriptional activity for utilization of both polysaccharides and LMW-DOM	1574:1649	SAR92 clade showed transcriptional activity for utilization of both polysaccharides and LMW-DOM; this may account for their abundance both in the peak and decline phases.
30786927	5	35	located	observed	743:750	arg1	comparison					795:804	an individual genome bin-based pairwise comparison	755:804	an individual genome bin-based pairwise comparison of gene expression	755:823	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	5	35	located	observed	743:750	arg2	correlation					672:682	A high correlation	665:682	A high correlation of gene expression between the peak and decline phases	665:737	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	11	36	from	phases	1759:1764	arg1	dominant					1743:1750	dominant	1743:1750	dominant	1743:1750	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	8	37	theme	organic	1280:1286	arg1	LMW-DOM					1296:1302	LMW-DOM	1296:1302	LMW-DOM	1296:1302	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	8	37	theme	organic	1280:1286	arg1	matter					1288:1293	low molecular weight-dissolved organic matter	1249:1293	low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes	1249:1332	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	0	38	theme	Genomic	0:6	arg1	analyses					31:38	Genomic and metatranscriptomic analyses	0:38	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya	0:89	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya.
30786927	0	39	theme	metatranscriptomic	12:29	arg1	analyses					31:38	Genomic and metatranscriptomic analyses	0:38	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya	0:89	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya.
30786927	3	40	theme	bacterial	468:476	arg1	activity					492:499	high bacterial heterotrophic activity	463:499	high bacterial heterotrophic activity	463:499	However, in the Amundsen Sea, most of this organic carbon does not reach the sediment but is degraded in the water column due to high bacterial heterotrophic activity.
30786927	9	41	from	predominant	1500:1510	arg1	ocean					1548:1552	the sea ice-covered oligotrophic ocean	1515:1552	the sea ice-covered oligotrophic ocean	1515:1552	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	12	42	theme	unique	1972:1977	arg1	potential					1989:1997	the unique metabolic potential	1968:1997	the unique metabolic potential of dominant bacteria of the Antarctic polynya	1968:2043	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	11	43	dep	polynya	1773:1779	arg1	bloom					1781:1785	bloom	1781:1785	bloom	1781:1785	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	12	44	theme	finer	2050:2054	arg1	level					2066:2070	a finer taxonomic level	2048:2070	a finer taxonomic level	2048:2070	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	13	45	theme	temporal	2112:2119	arg1	succession					2131:2140	temporal community succession	2112:2140	temporal community succession linked to the availability of substrates derived from the P. antarctica bloom	2112:2218	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	12	46	theme	in	1926:1927	arg1	expression					1939:1948	in situ gene expression	1926:1948	in situ gene expression	1926:1948	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	6	47	from	phase	903:907	arg1	dominant					882:889	dominant	882:889	dominant	882:889	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	8	48	theme	compatible	1315:1324	arg1	solutes					1326:1332	compatible solutes	1315:1332	compatible solutes	1315:1332	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	14	49	theme	various	2361:2367	arg1	polynyas					2369:2376	various polynyas	2361:2376	various polynyas	2361:2376	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	10	50	theme	LMW-DOM	1643:1649	arg1	utilization					1603:1613	utilization	1603:1613	utilization of both polysaccharides and LMW-DOM	1603:1649	SAR92 clade showed transcriptional activity for utilization of both polysaccharides and LMW-DOM; this may account for their abundance both in the peak and decline phases.
30786927	0	51	theme	remineralization	50:65	arg1	analyses					31:38	Genomic and metatranscriptomic analyses	0:38	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya	0:89	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya.
30786927	9	52	theme	sea	1519:1521	arg1	ocean					1548:1552	the sea ice-covered oligotrophic ocean	1515:1552	the sea ice-covered oligotrophic ocean	1515:1552	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	2	53	theme	water	248:252	arg1	column					254:259	the water column	244:259	the water column	244:259	Carbon fixed by phytoplankton in the water column is transferred to higher trophic levels, and finally, to the deep ocean.
30786927	10	54	theme	polysaccharides	1623:1637	arg1	utilization					1603:1613	utilization	1603:1613	utilization of both polysaccharides and LMW-DOM	1603:1649	SAR92 clade showed transcriptional activity for utilization of both polysaccharides and LMW-DOM; this may account for their abundance both in the peak and decline phases.
30786927	9	55	theme	oligotrophic	1535:1546	arg1	ocean					1548:1552	the sea ice-covered oligotrophic ocean	1515:1552	the sea ice-covered oligotrophic ocean	1515:1552	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	1	56	theme	intense	149:155	arg1	production					165:174	intense primary production	149:174	intense primary production	149:174	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	4	57	theme	different	557:565	arg1	phases					567:572	different phases	557:572	different phases of bloom	557:581	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	6	58	from	dominant	882:889	arg1	phase					903:907	the peak phase	894:907	the peak phase	894:907	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	14	59	theme	repeated	2332:2339	arg1	studies					2350:2356	repeated parallel studies	2332:2356	repeated parallel studies in various polynyas	2332:2376	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	1	60	from	Polynyas	103:110	arg1	Ocean					128:132	the Southern Ocean	115:132	the Southern Ocean	115:132	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	12	61	theme	gene	1934:1937	arg1	expression					1939:1948	in situ gene expression	1926:1948	in situ gene expression	1926:1948	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	7	62	theme	hydrolases	1137:1146	arg1	set					1121:1123	a distinct set	1110:1123	a distinct set of glycosyl hydrolases	1110:1146	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	7	62	theme	hydrolases	1137:1146	arg1	hydrolases					1137:1146	glycosyl hydrolases	1128:1146	glycosyl hydrolases	1128:1146	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	11	63	theme	polynya	1773:1779	arg1	phases					1759:1764	all phases	1755:1764	all phases of the polynya bloom	1755:1785	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	13	64	attach	derived	2183:2189	arg2	substrates					2172:2181	substrates	2172:2181	substrates derived from the P. antarctica bloom	2172:2218	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	13	64	attach	derived	2183:2189	arg1	bloom					2214:2218	bloom	2214:2218	bloom	2214:2218	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	14	65	theme	warming-related	2409:2423	arg1	changes					2425:2431	global warming-related changes	2402:2431	global warming-related changes in carbon remineralization	2402:2458	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	4	66	theme	key	530:532	arg1	genomes					544:550	12 key bacterial genomes	527:550	12 key bacterial genomes from different phases of bloom	527:581	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	7	67	theme	major	1045:1049	arg1	polymers					1051:1058	major polymers	1045:1058	major polymers	1045:1058	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	12	68	theme	reconstruction	1907:1920	arg1	analyses					1950:1957	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses	1887:1957	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses	1887:1957	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	2	69	theme	higher	279:284	arg1	levels					294:299	higher trophic levels	279:299	higher trophic levels	279:299	Carbon fixed by phytoplankton in the water column is transferred to higher trophic levels, and finally, to the deep ocean.
30786927	2	70	from	Carbon	211:216	arg1	column					254:259	the water column	244:259	the water column	244:259	Carbon fixed by phytoplankton in the water column is transferred to higher trophic levels, and finally, to the deep ocean.
30786927	8	71	theme	decline	1156:1162	arg1	phase					1164:1168	the decline phase	1152:1168	the decline phase	1152:1168	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	12	72	theme	taxonomic	2056:2064	arg1	level					2066:2070	a finer taxonomic level	2048:2070	a finer taxonomic level	2048:2070	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	11	73	theme	Ant4D3	1726:1731	arg1	clade					1733:1737	Ant4D3 clade	1726:1737	Ant4D3 clade	1726:1737	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	9	74	theme	Gammaproteobacteria	1369:1387	arg1	versatility					1354:1364	The versatility	1350:1364	The versatility of Gammaproteobacteria	1350:1387	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	12	75	theme	CONCLUSIONS	1887:1897	arg1	reconstruction					1907:1920	CONCLUSIONS Genomic reconstruction	1887:1920	CONCLUSIONS Genomic reconstruction	1887:1920	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	6	76	theme	transcriptional	918:932	arg1	activity					934:941	its transcriptional activity	914:941	its transcriptional activity	914:941	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	12	77	theme	metabolic	1979:1987	arg1	potential					1989:1997	the unique metabolic potential	1968:1997	the unique metabolic potential of dominant bacteria of the Antarctic polynya	1968:2043	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	2	78	theme	deep	322:325	arg1	ocean					327:331	the deep ocean	318:331	the deep ocean	318:331	Carbon fixed by phytoplankton in the water column is transferred to higher trophic levels, and finally, to the deep ocean.
30786927	7	79	theme	dominant	989:996	arg1	bins					1011:1014	Two dominant Polaribacter bins	985:1014	Two dominant Polaribacter bins	985:1014	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	5	80	theme	gene	809:812	arg1	expression					814:823	gene expression	809:823	gene expression	809:823	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	14	81	from	studies	2350:2356	arg1	polynyas					2369:2376	various polynyas	2361:2376	various polynyas	2361:2376	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	12	82	theme	polynya	2037:2043	arg1	potential					1989:1997	the unique metabolic potential	1968:1997	the unique metabolic potential of dominant bacteria of the Antarctic polynya	1968:2043	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	1	83	theme	Southern	119:126	arg1	Ocean					128:132	the Southern Ocean	115:132	the Southern Ocean	115:132	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	6	84	theme	mRNA	972:975	arg1	%					957:957	48.9%	953:957	48.9% of the total mRNA reads	953:981	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	6	84	theme	mRNA	972:975	arg1	mRNA					972:975	the total mRNA reads	962:981	the total mRNA reads	962:981	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	12	85	theme	bacteria	2011:2018	arg1	potential					1989:1997	the unique metabolic potential	1968:1997	the unique metabolic potential of dominant bacteria of the Antarctic polynya	1968:2043	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	14	86	theme	compositional	2252:2264	arg1	changes					2266:2272	compositional changes	2252:2272	compositional changes in phytoplankton from P. antarctica to diatoms	2252:2319	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	0	87	theme	Antarctic	73:81	arg1	polynya					83:89	an Antarctic polynya	70:89	an Antarctic polynya	70:89	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya.
30786927	9	88	theme	carbon-rich	1434:1444	arg1	waters					1454:1459	organic carbon-rich polynya waters	1426:1459	organic carbon-rich polynya waters	1426:1459	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	0	89	from	analyses	31:38	arg1	polynya					83:89	an Antarctic polynya	70:89	an Antarctic polynya	70:89	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya.
30786927	11	90	from	roles	1812:1816	arg1	remineralization					1843:1858	LMW-DOM remineralization	1835:1858	LMW-DOM remineralization	1835:1858	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	4	91	theme	organic	632:638	arg1	remineralization					647:662	organic carbon remineralization	632:662	organic carbon remineralization	632:662	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	7	92	theme	glycosyl	1128:1135	arg1	hydrolases					1137:1146	glycosyl hydrolases	1128:1146	glycosyl hydrolases	1128:1146	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	4	93	from	phases	567:572	arg1	genomes					544:550	12 key bacterial genomes	527:550	12 key bacterial genomes from different phases of bloom	527:581	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	1	94	theme	primary	157:163	arg1	production					165:174	intense primary production	149:174	intense primary production	149:174	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	10	95	dep	abundance	1679:1687	arg1	both					1689:1692	both	1689:1692	both	1689:1692	SAR92 clade showed transcriptional activity for utilization of both polysaccharides and LMW-DOM; this may account for their abundance both in the peak and decline phases.
30786927	5	96	theme	gene	687:690	arg1	expression					692:701	gene expression	687:701	gene expression	687:701	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	14	97	from	changes	2425:2431	arg1	remineralization					2443:2458	carbon remineralization	2436:2458	carbon remineralization	2436:2458	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	14	98	from	changes	2266:2272	arg1	phytoplankton					2277:2289	phytoplankton	2277:2289	phytoplankton from P. antarctica to diatoms	2277:2319	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	14	98	from	changes	2266:2272	arg1	antarctica					2299:2308	antarctica	2299:2308	antarctica	2299:2308	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	7	99	theme	distinct	1112:1119	arg1	set					1121:1123	a distinct set	1110:1123	a distinct set of glycosyl hydrolases	1110:1146	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	7	99	theme	distinct	1112:1119	arg1	hydrolases					1137:1146	glycosyl hydrolases	1128:1146	glycosyl hydrolases	1128:1146	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	9	100	theme	SAR11	1472:1476	arg1	predominant					1500:1510	predominant	1500:1510	predominant	1500:1510	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	9	100	theme	SAR11	1472:1476	arg1	clade					1478:1482	the SAR11 clade	1468:1482	the SAR11 clade	1468:1482	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	6	101	dep	mRNA	972:975	arg1	reads					977:981	reads	977:981	reads	977:981	Polaribacter belonging to Bacteroidetes was found to be dominant in the peak phase, and its transcriptional activity was high (48.9% of the total mRNA reads).
30786927	8	102	theme	low	1249:1251	arg1	LMW-DOM					1296:1302	LMW-DOM	1296:1302	LMW-DOM	1296:1302	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	8	102	theme	low	1249:1251	arg1	matter					1288:1293	low molecular weight-dissolved organic matter	1249:1293	low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes	1249:1332	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	5	103	theme	individual	758:767	arg1	comparison					795:804	an individual genome bin-based pairwise comparison	755:804	an individual genome bin-based pairwise comparison of gene expression	755:823	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	4	104	dep	RESULTS	502:508	arg1	reconstructed					513:525	reconstructed	513:525	reconstructed 12 key bacterial genomes from different phases of bloom	513:581	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	4	104	dep	RESULTS	502:508	arg1	analyzed					587:594	analyzed	587:594	analyzed the expression of genes involved in organic carbon remineralization	587:662	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	1	105	theme	BACKGROUND	92:101	arg1	Polynyas					103:110	BACKGROUND Polynyas	92:110	BACKGROUND Polynyas in the Southern Ocean	92:132	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	1	105	theme	BACKGROUND	92:101	arg1	regions					138:144	regions	138:144	regions of intense primary production	138:174	BACKGROUND Polynyas in the Southern Ocean are regions of intense primary production, mainly by Phaeocystis antarctica.
30786927	8	106	theme	weight-dissolved	1263:1278	arg1	LMW-DOM					1296:1302	LMW-DOM	1296:1302	LMW-DOM	1296:1302	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	8	106	theme	weight-dissolved	1263:1278	arg1	matter					1288:1293	low molecular weight-dissolved organic matter	1249:1293	low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes	1249:1332	In the decline phase, Gammaproteobacteria (Ant4D3, SUP05, and SAR92), with the potential to utilize low molecular weight-dissolved organic matter (LMW-DOM) including compatible solutes, was increased.
30786927	11	107	theme	crucial	1804:1810	arg1	roles					1812:1816	the crucial roles	1800:1816	the crucial roles of this clade in LMW-DOM remineralization	1800:1858	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	5	108	theme	bin-based	776:784	arg1	comparison					795:804	an individual genome bin-based pairwise comparison	755:804	an individual genome bin-based pairwise comparison of gene expression	755:823	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	5	109	theme	genome	769:774	arg1	comparison					795:804	an individual genome bin-based pairwise comparison	755:804	an individual genome bin-based pairwise comparison of gene expression	755:823	A high correlation of gene expression between the peak and decline phases was observed in an individual genome bin-based pairwise comparison of gene expression.
30786927	3	110	theme	Amundsen	350:357	arg1	Sea					359:361	the Amundsen Sea	346:361	the Amundsen Sea	346:361	However, in the Amundsen Sea, most of this organic carbon does not reach the sediment but is degraded in the water column due to high bacterial heterotrophic activity.
30786927	12	111	dep	in	1926:1927	arg1	situ					1929:1932	situ	1929:1932	situ	1929:1932	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	7	112	contain	had	1016:1018	arg1	bins					1011:1014	Two dominant Polaribacter bins	985:1014	Two dominant Polaribacter bins	985:1014	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	7	112	contain	had	1016:1018	arg2	potential					1024:1032	the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases	1020:1146	the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases	1020:1146	Two dominant Polaribacter bins had the potential to utilize major polymers in P. antarctica, chrysolaminarin and xylan, with a distinct set of glycosyl hydrolases.
30786927	11	113	theme	LMW-DOM	1835:1841	arg1	remineralization					1843:1858	LMW-DOM remineralization	1835:1858	LMW-DOM remineralization	1835:1858	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	0	114	theme	carbon	43:48	arg1	remineralization					50:65	carbon remineralization	43:65	carbon remineralization	43:65	Genomic and metatranscriptomic analyses of carbon remineralization in an Antarctic polynya.
30786927	3	115	theme	organic	377:383	arg1	carbon					385:390	this organic carbon	372:390	this organic carbon	372:390	However, in the Amundsen Sea, most of this organic carbon does not reach the sediment but is degraded in the water column due to high bacterial heterotrophic activity.
30786927	11	116	theme	clade	1826:1830	arg1	roles					1812:1816	the crucial roles	1800:1816	the crucial roles of this clade in LMW-DOM remineralization	1800:1858	Ant4D3 clade was dominant in all phases of the polynya bloom, implicating the crucial roles of this clade in LMW-DOM remineralization in the Antarctic polynyas.
30786927	13	117	theme	community	2121:2129	arg1	succession					2131:2140	temporal community succession	2112:2140	temporal community succession linked to the availability of substrates derived from the P. antarctica bloom	2112:2218	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	2	118	theme	fixed	218:222	arg1	Carbon					211:216	Carbon fixed	211:222	Carbon fixed by phytoplankton in the water column	211:259	Carbon fixed by phytoplankton in the water column is transferred to higher trophic levels, and finally, to the deep ocean.
30786927	3	119	theme	water	443:447	arg1	column					449:454	the water column	439:454	the water column due to high bacterial heterotrophic activity	439:499	However, in the Amundsen Sea, most of this organic carbon does not reach the sediment but is degraded in the water column due to high bacterial heterotrophic activity.
30786927	13	120	used	used	2096:2099	arg2	information					2077:2087	The information	2073:2087	The information	2073:2087	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	9	121	theme	ice-covered	1523:1533	arg1	ocean					1548:1552	the sea ice-covered oligotrophic ocean	1515:1552	the sea ice-covered oligotrophic ocean	1515:1552	The versatility of Gammaproteobacteria may contribute to their abundance in organic carbon-rich polynya waters, while the SAR11 clade was found to be predominant in the sea ice-covered oligotrophic ocean.
30786927	14	122	theme	parallel	2341:2348	arg1	studies					2350:2356	repeated parallel studies	2332:2356	repeated parallel studies in various polynyas	2332:2376	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	12	123	theme	expression	1939:1948	arg1	analyses					1950:1957	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses	1887:1957	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses	1887:1957	CONCLUSIONS Genomic reconstruction and in situ gene expression analyses revealed the unique metabolic potential of dominant bacteria of the Antarctic polynya at a finer taxonomic level.
30786927	14	124	theme	carbon	2436:2441	arg1	remineralization					2443:2458	carbon remineralization	2436:2458	carbon remineralization	2436:2458	Global warming has resulted in compositional changes in phytoplankton from P. antarctica to diatoms, and thus, repeated parallel studies in various polynyas are required to predict global warming-related changes in carbon remineralization.
30786927	4	125	theme	bloom	577:581	arg1	phases					567:572	different phases	557:572	different phases of bloom	557:581	RESULTS We reconstructed 12 key bacterial genomes from different phases of bloom and analyzed the expression of genes involved in organic carbon remineralization.
30786927	13	126	attach	linked	2142:2147	arg1	availability					2156:2167	the availability	2152:2167	the availability of substrates derived from the P. antarctica bloom	2152:2218	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	13	126	attach	linked	2142:2147	arg2	succession					2131:2140	temporal community succession	2112:2140	temporal community succession linked to the availability of substrates derived from the P. antarctica bloom	2112:2218	The information can be used to predict temporal community succession linked to the availability of substrates derived from the P. antarctica bloom.
30786927	3	127	theme	high	463:466	arg1	activity					492:499	high bacterial heterotrophic activity	463:499	high bacterial heterotrophic activity	463:499	However, in the Amundsen Sea, most of this organic carbon does not reach the sediment but is degraded in the water column due to high bacterial heterotrophic activity.
30592403	4	0	theme	multiacrylate	553:565	arg1	groups					571:576	multiacrylate end groups	553:576	multiacrylate end groups	553:576	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	6	1	theme	thiolate	1048:1055	arg1	groups					1069:1074	thiolate and quinone groups	1048:1074	groups	1069:1074	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	0	2	theme	ROS-Sensitive	91:103	arg1	Hydrogels					105:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	5	3	theme	polydopamine	728:739	arg1	deposited					753:761	a polydopamine (PDA) layer deposited	726:761	a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly	726:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	4	4	theme	ROS-sensitive	515:527	arg1	HB-PBAE					539:545	HB-PBAE	539:545	HB-PBAE	539:545	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	4	4	theme	ROS-sensitive	515:527	arg1	macromer					529:536	A hyperbranched ROS-sensitive macromer	499:536	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups	499:576	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	5	5	theme	TIIA	786:789	arg1	nanoparticles					792:804	the tanshinone IIA (TIIA) nanoparticles	766:804	the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly	766:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	5	5	theme	TIIA	786:789	arg1	NPs					807:809	NPs	807:809	NPs	807:809	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	7	6	theme	degradation	1136:1146	arg1	behavior					1148:1155	The in vivo degradation behavior	1124:1155	The in vivo degradation behavior of the hydrogels	1124:1172	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	7	7	from	that	1278:1281	arg1	behavior					1237:1244	a much slower degradation behavior	1211:1244	a much slower degradation behavior that is markedly different from that of in vitro	1211:1293	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	7	7	from	that	1278:1281	arg1	different					1263:1271	different	1263:1271	different	1263:1271	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	8	8	theme	hydrogel	1375:1382	arg1	injection					1384:1392	hydrogel injection	1375:1392	hydrogel injection	1375:1392	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	5	9	theme	PDA	742:744	arg1	deposited					753:761	a polydopamine (PDA) layer deposited	726:761	a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly	726:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	5	10	theme	dopamine	677:684	arg1	polymerization					686:699	dopamine polymerization	677:699	dopamine polymerization	677:699	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	6	11	theme	chemical	1020:1027	arg1	cross-link					1029:1038	the chemical cross-link	1016:1038	the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels	1016:1121	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	8	12	theme	significant	1311:1321	arg1	improvement					1323:1333	a significant improvement	1309:1333	a significant improvement of cardiac functions	1309:1354	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	7	13	theme	in	1128:1129	arg1	behavior					1148:1155	The in vivo degradation behavior	1124:1155	The in vivo degradation behavior of the hydrogels	1124:1172	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	6	14	theme	hydrogels	1113:1121	arg1	modulus					1102:1108	the modulus	1098:1108	the modulus of hydrogels	1098:1121	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	4	15	with	macromer	529:536	arg1	groups					571:576	multiacrylate end groups	553:576	multiacrylate end groups	553:576	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	7	16	theme	slower	1218:1223	arg1	behavior					1237:1244	a much slower degradation behavior	1211:1244	a much slower degradation behavior that is markedly different from that of in vitro	1211:1293	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	7	16	theme	slower	1218:1223	arg1	different					1263:1271	different	1263:1271	different	1263:1271	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	6	17	theme	in	941:942	arg1	hydrogel					949:956	an in situ hydrogel	938:956	an in situ hydrogel	938:956	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	7	18	dep	in	1128:1129	arg1	vivo					1131:1134	vivo	1131:1134	vivo	1131:1134	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	6	19	theme	@	969:969	arg1	NPs					974:976	TIIA@PDA NPs	965:976	TIIA@PDA NPs	965:976	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	0	20	theme	Postinfarcted	11:23	arg1	Functions					33:41	Postinfarcted Cardiac Functions	11:41	Postinfarcted Cardiac Functions	11:41	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	1	21	contain	possess	169:175	arg2	potential					182:190	huge potential	177:190	huge potential for applications in tissue engineering	177:229	Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering.
30592403	1	21	contain	possess	169:175	arg1	hydrogels					139:147	Drug-loaded injectable hydrogels	116:147	Drug-loaded injectable hydrogels	116:147	Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering.
30592403	2	22	theme	myocardial	351:360	arg1	infarction					362:371	myocardial infarction	351:371	myocardial infarction face a huge challenge	351:393	However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge.
30592403	1	23	theme	tissue	212:217	arg1	engineering					219:229	tissue engineering	212:229	tissue engineering	212:229	Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering.
30592403	3	24	theme	ROS-sensitive	417:429	arg1	hydrogel					442:449	an ROS-sensitive injectable hydrogel	414:449	an ROS-sensitive injectable hydrogel strengthened by self-nanodrugs	414:480	In this research, an ROS-sensitive injectable hydrogel strengthened by self-nanodrugs was constructed.
30592403	8	25	theme	factors	1525:1531	arg1	expression					1498:1507	the expression	1494:1507	the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α	1494:1563	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	5	26	theme	simple	652:657	arg1	protocol					659:666	a simple protocol	650:666	a simple protocol based on dopamine polymerization	650:699	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	5	26	theme	simple	652:657	arg1	Meanwhile					639:647	Meanwhile	639:647	Meanwhile	639:647	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	1	27	theme	Drug-loaded	116:126	arg1	hydrogels					139:147	Drug-loaded injectable hydrogels	116:147	Drug-loaded injectable hydrogels	116:147	Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering.
30592403	4	28	theme	Michael	621:627	arg1	addition					629:636	dynamic controlled Michael addition	602:636	dynamic controlled Michael addition	602:636	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	1	29	theme	injectable	128:137	arg1	hydrogels					139:147	Drug-loaded injectable hydrogels	116:147	Drug-loaded injectable hydrogels	116:147	Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering.
30592403	8	30	theme	infarction	1448:1457	arg1	size					1459:1462	decreased infarction size	1438:1462	decreased infarction size	1438:1462	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	2	31	dep	infarction	362:371	arg1	face					373:376	face	373:376	face	373:376	However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge.
30592403	5	32	theme	tanshinone	770:779	arg1	nanoparticles					792:804	the tanshinone IIA (TIIA) nanoparticles	766:804	the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly	766:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	5	32	theme	tanshinone	770:779	arg1	NPs					807:809	NPs	807:809	NPs	807:809	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	4	33	theme	hyperbranched	501:513	arg1	HB-PBAE					539:545	HB-PBAE	539:545	HB-PBAE	539:545	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	4	33	theme	hyperbranched	501:513	arg1	macromer					529:536	A hyperbranched ROS-sensitive macromer	499:536	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups	499:576	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	8	34	theme	increased	1406:1414	arg1	fraction					1425:1432	increased ejection fraction	1406:1432	increased ejection fraction	1406:1432	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	6	35	theme	TIIA	965:968	arg1	NPs					974:976	TIIA@PDA NPs	965:976	TIIA@PDA NPs	965:976	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	5	36	theme	spontaneous	824:834	arg1	self-assembly					848:860	spontaneous hydrophobic self-assembly	824:860	spontaneous hydrophobic self-assembly	824:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	5	37	theme	IIA	781:783	arg1	nanoparticles					792:804	the tanshinone IIA (TIIA) nanoparticles	766:804	the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly	766:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	5	37	theme	IIA	781:783	arg1	NPs					807:809	NPs	807:809	NPs	807:809	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	7	38	theme	hydrogels	1164:1172	arg1	behavior					1148:1155	The in vivo degradation behavior	1124:1155	The in vivo degradation behavior of the hydrogels	1124:1172	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	5	39	theme	hydrophobic	836:846	arg1	self-assembly					848:860	spontaneous hydrophobic self-assembly	824:860	spontaneous hydrophobic self-assembly	824:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	6	40	dep	in	941:942	arg1	situ					944:947	situ	944:947	situ	944:947	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	8	41	theme	expression	1498:1507	arg1	inhibition					1480:1489	inhibition	1480:1489	inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α	1480:1563	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	2	42	theme	loading	261:267	arg1	capacity					269:276	the drug loading capacity	252:276	the drug loading capacity	252:276	However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge.
30592403	6	43	theme	PDA	970:972	arg1	NPs					974:976	TIIA@PDA NPs	965:976	TIIA@PDA NPs	965:976	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	3	44	theme	injectable	431:440	arg1	hydrogel					442:449	an ROS-sensitive injectable hydrogel	414:449	an ROS-sensitive injectable hydrogel strengthened by self-nanodrugs	414:480	In this research, an ROS-sensitive injectable hydrogel strengthened by self-nanodrugs was constructed.
30592403	7	45	theme	degradation	1225:1235	arg1	behavior					1237:1244	a much slower degradation behavior	1211:1244	a much slower degradation behavior that is markedly different from that of in vitro	1211:1293	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	7	45	theme	degradation	1225:1235	arg1	different					1263:1271	different	1263:1271	different	1263:1271	The in vivo degradation behavior of the hydrogels was characterized by MRI, exhibiting a much slower degradation behavior that is markedly different from that of in vitro.
30592403	0	46	theme	PDA	61:63	arg1	Hydrogels					105:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	2	47	theme	drug	256:259	arg1	capacity					269:276	the drug loading capacity	252:276	the drug loading capacity	252:276	However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge.
30592403	2	48	theme	huge	380:383	arg1	challenge					385:393	a huge challenge	378:393	a huge challenge	378:393	However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge.
30592403	0	49	theme	TIIA	56:59	arg1	Hydrogels					105:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	4	50	theme	controlled	610:619	arg1	addition					629:636	dynamic controlled Michael addition	602:636	dynamic controlled Michael addition	602:636	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	5	51	theme	layer	747:751	arg1	deposited					753:761	a polydopamine (PDA) layer deposited	726:761	a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly	726:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	8	52	theme	inflammation	1512:1523	arg1	IL-1β					1542:1546	IL-1β	1542:1546	IL-1β	1542:1546	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	8	52	theme	inflammation	1512:1523	arg1	factors					1525:1531	inflammation factors	1512:1531	inflammation factors	1512:1531	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	8	52	theme	inflammation	1512:1523	arg1	IL-6					1549:1552	IL-6	1549:1552	IL-6	1549:1552	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	8	52	theme	inflammation	1512:1523	arg1	TNF-α					1559:1563	TNF-α	1559:1563	TNF-α	1559:1563	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	8	53	theme	decreased	1438:1446	arg1	size					1459:1462	decreased infarction size	1438:1462	decreased infarction size	1438:1462	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	0	54	link	Nanoparticle-Cross-linked	65:89	arg1	Hydrogels					105:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	4	55	theme	dynamic	602:608	arg1	addition					629:636	dynamic controlled Michael addition	602:636	dynamic controlled Michael addition	602:636	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	2	56	theme	release	297:303	arg1	system					305:310	the release system	293:310	the release system to adapt to the microenvironment after myocardial infarction face a huge challenge	293:393	However, increasing the drug loading capacity and regulating the release system to adapt to the microenvironment after myocardial infarction face a huge challenge.
30592403	8	57	theme	fraction	1425:1432	arg1	terms					1397:1401	terms	1397:1401	terms of increased ejection fraction and decreased infarction size	1397:1462	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	8	58	theme	ejection	1416:1423	arg1	fraction					1425:1432	increased ejection fraction	1406:1432	increased ejection fraction	1406:1432	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	5	59	from	deposited	753:761	arg1	nanoparticles					792:804	the tanshinone IIA (TIIA) nanoparticles	766:804	the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly	766:860	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	5	59	from	deposited	753:761	arg1	NPs					807:809	NPs	807:809	NPs	807:809	Meanwhile, a simple protocol based on dopamine polymerization was employed to generate a polydopamine (PDA) layer deposited on the tanshinone IIA (TIIA) nanoparticles (NPs) formed from spontaneous hydrophobic self-assembly.
30592403	6	60	theme	hyaluronic	906:915	arg1	acid					917:920	thiolate-modified hyaluronic acid	888:920	thiolate-modified hyaluronic acid (HA-SH)	888:928	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	6	60	theme	hyaluronic	906:915	arg1	HA-SH					923:927	HA-SH	923:927	HA-SH	923:927	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	8	61	theme	size	1459:1462	arg1	terms					1397:1401	terms	1397:1401	terms of increased ejection fraction and decreased infarction size	1397:1462	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	8	62	theme	cardiac	1338:1344	arg1	functions					1346:1354	cardiac functions	1338:1354	cardiac functions	1338:1354	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	0	63	theme	Nanoparticle-Cross-linked	65:89	arg1	Hydrogels					105:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	6	64	theme	thiolate-modified	888:904	arg1	acid					917:920	thiolate-modified hyaluronic acid	888:920	thiolate-modified hyaluronic acid (HA-SH)	888:928	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	6	64	theme	thiolate-modified	888:904	arg1	HA-SH					923:927	HA-SH	923:927	HA-SH	923:927	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	6	65	from	groups	1069:1074	arg1	PDA					1079:1081	PDA	1079:1081	PDA	1079:1081	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	8	66	theme	functions	1346:1354	arg1	improvement					1323:1333	a significant improvement	1309:1333	a significant improvement of cardiac functions	1309:1354	Importantly, a significant improvement of cardiac functions was achieved after hydrogel injection in terms of increased ejection fraction and decreased infarction size, accompanied by inhibition of the expression of inflammation factors, such as IL-1β, IL-6, and TNF-α.
30592403	6	67	theme	quinone	1061:1067	arg1	groups					1069:1074	thiolate and quinone groups	1048:1074	groups	1069:1074	The HB-PBAE reacted with thiolate-modified hyaluronic acid (HA-SH) to form an in situ hydrogel, where TIIA@PDA NPs can be conveniently entrapped through the chemical cross-link between thiolate and quinone groups on PDA, which doubles the modulus of hydrogels.
30592403	0	68	theme	@	60:60	arg1	Hydrogels					105:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels	56:113	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	4	69	theme	end	567:569	arg1	groups					571:576	multiacrylate end groups	553:576	multiacrylate end groups	553:576	A hyperbranched ROS-sensitive macromer (HB-PBAE) with multiacrylate end groups was synthesized through dynamic controlled Michael addition.
30592403	0	70	theme	Cardiac	25:31	arg1	Functions					33:41	Postinfarcted Cardiac Functions	11:41	Postinfarcted Cardiac Functions	11:41	Rebuilding Postinfarcted Cardiac Functions by Injecting TIIA@PDA Nanoparticle-Cross-linked ROS-Sensitive Hydrogels.
30592403	1	71	from	applications	196:207	arg1	engineering					219:229	tissue engineering	212:229	tissue engineering	212:229	Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering.
30592403	1	72	theme	huge	177:180	arg1	potential					182:190	huge potential	177:190	huge potential for applications in tissue engineering	177:229	Drug-loaded injectable hydrogels have been proven to possess huge potential for applications in tissue engineering.
30333848	14	0	theme	pectic	2059:2064	arg1	elements					2077:2084	that pectic structural elements	2054:2084	that pectic structural elements	2054:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	7	1	theme	α-arabinopyranose	1186:1202	arg1	residues					1204:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	10	2	theme	detected	1499:1506	arg1	variations					1519:1528	previously detected structural variations	1488:1528	previously detected structural variations	1488:1528	It was demonstrated that arabinan decomposition is independent of previously detected structural variations.
30333848	7	3	theme	β-arabinofuranose	1164:1180	arg1	residues					1204:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	3	4	theme	chain	546:550	arg1	substituents					552:563	side chain substituents	541:563	side chain substituents	541:563	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	4	5	theme	fine	678:681	arg1	structures					683:692	fine structures	678:692	fine structures of arabinans and galactans	678:719	Therefore, fine structures of arabinans and galactans were analyzed in 14 apple cultivars before and after storage.
30333848	7	6	theme	structural	1136:1145	arg1	elements					1147:1154	rare structural elements	1131:1154	rare structural elements such as β-arabinofuranose and α-arabinopyranose residues	1131:1211	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	7	6	theme	structural	1136:1145	arg1	residues					1204:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	10	7	theme	variations	1519:1528	arg1	independent					1473:1483	independent	1473:1483	independent	1473:1483	It was demonstrated that arabinan decomposition is independent of previously detected structural variations.
30333848	2	8	theme	pectic	319:324	arg1	chains					331:336	neutral pectic side chains	311:336	neutral pectic side chains (arabinans and galactans)	311:362	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	8	9	theme	methods	1264:1270	arg1	combination					1245:1255	the combination	1241:1255	the combination of all methods	1241:1270	In addition, the combination of all methods indicated structural differences with regard to ramification position or patterns.
30333848	12	10	theme	endo-galactanase	1736:1751	arg1	hydrolysates					1753:1764	endo-galactanase hydrolysates	1736:1764	endo-galactanase hydrolysates	1736:1764	Analysis of endo-galactanase hydrolysates showed decreased portions of galactan-bound, terminal α-arabinopyranose units after storage.
30333848	6	11	link	β-1,4-linked	1035:1046	arg1	galactans					1048:1056	linear β-1,4-linked galactans	1028:1056	linear β-1,4-linked galactans	1028:1056	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	14	12	from	elements	2077:2084	arg1	complexity					1999:2008	the high complexity	1990:2008	the high complexity of neutral pectin side chains in apples and that pectic structural elements	1990:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	14	13	theme	structural	2066:2075	arg1	elements					2077:2084	that pectic structural elements	2054:2084	that pectic structural elements	2054:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	8	14	theme	structural	1282:1291	arg1	differences					1293:1303	structural differences	1282:1303	structural differences with regard to ramification position or patterns	1282:1352	In addition, the combination of all methods indicated structural differences with regard to ramification position or patterns.
30333848	1	15	theme	Physiological	117:129	arg1	properties					144:153	Physiological and textural properties	117:153	Physiological and textural properties of apples	117:163	Physiological and textural properties of apples are greatly influenced by both cultivar and structural composition of their pectic polysaccharides.
30333848	7	16	theme	profiling	1109:1117	arg1	approaches					1119:1128	enzymatic profiling approaches	1099:1128	enzymatic profiling approaches	1099:1128	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	14	17	from	complexity	1999:2008	arg1	elements					2077:2084	that pectic structural elements	2054:2084	that pectic structural elements	2054:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	14	17	from	complexity	1999:2008	arg1	apples					2043:2048	apples	2043:2048	apples	2043:2048	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	3	18	contain	have	466:469	arg1	polymers					457:464	these complex polymers	443:464	these complex polymers	443:464	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	3	18	contain	have	466:469	arg2	heterogeneity					489:501	a high structural heterogeneity	471:501	a high structural heterogeneity	471:501	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	13	19	theme	postharvest	1916:1926	arg1	decomposition					1937:1949	postharvest galactan decomposition	1916:1949	postharvest galactan decomposition	1916:1949	Therefore, these residues are most likely removed during postharvest galactan decomposition.
30333848	3	20	theme	residues	597:604	arg1	substitution					569:580	substitution	569:580	substitution of neighboring residues	569:604	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	3	20	theme	residues	597:604	arg1	substituents					552:563	side chain substituents	541:563	side chain substituents	541:563	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	5	21	theme	side	950:953	arg1	chains					955:960	the neutral side chains	938:960	the neutral side chains of pectins	938:971	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	4	22	theme	apple	741:745	arg1	cultivars					747:755	14 apple cultivars	738:755	14 apple cultivars	738:755	Therefore, fine structures of arabinans and galactans were analyzed in 14 apple cultivars before and after storage.
30333848	3	23	theme	conventional	634:645	arg1	methods					658:664	conventional analytical methods	634:664	conventional analytical methods	634:664	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	1	24	theme	textural	135:142	arg1	properties					144:153	Physiological and textural properties	117:153	Physiological and textural properties of apples	117:163	Physiological and textural properties of apples are greatly influenced by both cultivar and structural composition of their pectic polysaccharides.
30333848	11	25	theme	containing	1622:1631	arg1	chains					1638:1643	β-arabinofuranose containing side chains	1604:1643	β-arabinofuranose containing side chains	1604:1643	In addition, analysis of endo-arabinanase hydrolysates demonstrated that β-arabinofuranose containing side chains are enriched after storage and may play a major role in postharvest processes.
30333848	14	26	theme	pectin	2021:2026	arg1	chains					2033:2038	neutral pectin side chains	2013:2038	neutral pectin side chains in apples and that pectic structural elements	2013:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	0	27	theme	Cultivars	76:84	arg1	Galactans					54:62	Galactans	54:62	Galactans	54:62	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	0	27	theme	Cultivars	76:84	arg1	Arabinans					40:48	Arabinans	40:48	Arabinans	40:48	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	6	28	theme	β-1,4-linked	1035:1046	arg1	galactans					1048:1056	linear β-1,4-linked galactans	1028:1056	linear β-1,4-linked galactans	1028:1056	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	2	29	theme	previous	268:275	arg1	studies					277:283	previous studies	268:283	previous studies	268:283	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	12	30	theme	α-arabinopyranose	1820:1836	arg1	units					1838:1842	galactan-bound, terminal α-arabinopyranose units	1795:1842	galactan-bound, terminal α-arabinopyranose units	1795:1842	Analysis of endo-galactanase hydrolysates showed decreased portions of galactan-bound, terminal α-arabinopyranose units after storage.
30333848	14	31	theme	chains	2033:2038	arg1	complexity					1999:2008	the high complexity	1990:2008	the high complexity of neutral pectin side chains in apples and that pectic structural elements	1990:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	2	32	theme	fruit	389:393	arg1	development					395:405	fruit development	389:405	fruit development	389:405	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	0	33	theme	Cold	103:106	arg1	Storage					108:114	Cold Storage	103:114	Cold Storage	103:114	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	9	34	theme	branched	1402:1409	arg1	arabinans					1411:1419	branched arabinans	1402:1419	branched arabinans	1402:1419	Cold storage resulted in decreased portions of branched arabinans.
30333848	0	35	theme	Detailed	0:7	arg1	Characterization					20:35	Detailed Structural Characterization	0:35	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.	0:115	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	14	36	theme	side	2028:2031	arg1	chains					2033:2038	neutral pectin side chains	2013:2038	neutral pectin side chains in apples and that pectic structural elements	2013:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	11	37	theme	hydrolysates	1573:1584	arg1	analysis					1544:1551	analysis	1544:1551	analysis of endo-arabinanase hydrolysates	1544:1584	In addition, analysis of endo-arabinanase hydrolysates demonstrated that β-arabinofuranose containing side chains are enriched after storage and may play a major role in postharvest processes.
30333848	3	38	theme	complex	449:455	arg1	polymers					457:464	these complex polymers	443:464	these complex polymers	443:464	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	0	39	theme	Arabinans	40:48	arg1	Characterization					20:35	Detailed Structural Characterization	0:35	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.	0:115	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	14	40	theme	study	1972:1976	arg1	results					1956:1962	The results	1952:1962	The results of this study	1952:1976	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	12	41	dep	galactan-bound	1795:1808	arg1	terminal					1811:1818	terminal	1811:1818	terminal	1811:1818	Analysis of endo-galactanase hydrolysates showed decreased portions of galactan-bound, terminal α-arabinopyranose units after storage.
30333848	5	42	theme	methylation	820:830	arg1	analysis					832:839	methylation analysis	820:839	methylation analysis	820:839	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	3	43	theme	high	473:476	arg1	heterogeneity					489:501	a high structural heterogeneity	471:501	a high structural heterogeneity	471:501	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	14	44	from	chains	2033:2038	arg1	elements					2077:2084	that pectic structural elements	2054:2084	that pectic structural elements	2054:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	14	44	from	chains	2033:2038	arg1	apples					2043:2048	apples	2043:2048	apples	2043:2048	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	3	45	theme	structural	513:522	arg1	substitution					569:580	substitution	569:580	substitution of neighboring residues	569:604	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	3	45	theme	structural	513:522	arg1	substituents					552:563	side chain substituents	541:563	side chain substituents	541:563	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	3	45	theme	structural	513:522	arg1	elements					524:531	some structural elements	508:531	some structural elements such as side chain substituents and substitution of neighboring residues	508:604	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	14	46	from	apples	2043:2048	arg1	complexity					1999:2008	the high complexity	1990:2008	the high complexity of neutral pectin side chains in apples and that pectic structural elements	1990:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	1	47	theme	pectic	241:246	arg1	polysaccharides					248:262	their pectic polysaccharides	235:262	their pectic polysaccharides	235:262	Physiological and textural properties of apples are greatly influenced by both cultivar and structural composition of their pectic polysaccharides.
30333848	14	48	theme	postharvest	2111:2121	arg1	modifications					2123:2135	postharvest modifications	2111:2135	postharvest modifications	2111:2135	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	3	49	theme	side	541:544	arg1	substituents					552:563	side chain substituents	541:563	side chain substituents	541:563	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	14	50	theme	neutral	2013:2019	arg1	chains					2033:2038	neutral pectin side chains	2013:2038	neutral pectin side chains in apples and that pectic structural elements	2013:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	0	51	theme	Galactans	54:62	arg1	Characterization					20:35	Detailed Structural Characterization	0:35	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.	0:115	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	13	52	theme	galactan	1928:1935	arg1	decomposition					1937:1949	postharvest galactan decomposition	1916:1949	postharvest galactan decomposition	1916:1949	Therefore, these residues are most likely removed during postharvest galactan decomposition.
30333848	5	53	theme	conventional	791:802	arg1	methods					804:810	conventional methods	791:810	conventional methods such as methylation analysis	791:839	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	5	53	theme	conventional	791:802	arg1	analysis					832:839	methylation analysis	820:839	methylation analysis	820:839	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	7	54	theme	rare	1131:1134	arg1	elements					1147:1154	rare structural elements	1131:1154	rare structural elements such as β-arabinofuranose and α-arabinopyranose residues	1131:1211	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	7	54	theme	rare	1131:1134	arg1	residues					1204:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	β-arabinofuranose and α-arabinopyranose residues	1164:1211	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	11	55	theme	postharvest	1701:1711	arg1	processes					1713:1721	postharvest processes	1701:1721	postharvest processes	1701:1721	In addition, analysis of endo-arabinanase hydrolysates demonstrated that β-arabinofuranose containing side chains are enriched after storage and may play a major role in postharvest processes.
30333848	2	56	theme	side	326:329	arg1	chains					331:336	neutral pectic side chains	311:336	neutral pectic side chains (arabinans and galactans)	311:362	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	12	57	theme	hydrolysates	1753:1764	arg1	Analysis					1724:1731	Analysis	1724:1731	Analysis of endo-galactanase hydrolysates	1724:1764	Analysis of endo-galactanase hydrolysates showed decreased portions of galactan-bound, terminal α-arabinopyranose units after storage.
30333848	8	58	theme	ramification	1320:1331	arg1	position					1333:1340	ramification position	1320:1340	ramification position	1320:1340	In addition, the combination of all methods indicated structural differences with regard to ramification position or patterns.
30333848	11	59	theme	major	1687:1691	arg1	role					1693:1696	a major role	1685:1696	a major role	1685:1696	In addition, analysis of endo-arabinanase hydrolysates demonstrated that β-arabinofuranose containing side chains are enriched after storage and may play a major role in postharvest processes.
30333848	10	60	theme	structural	1508:1517	arg1	variations					1519:1528	previously detected structural variations	1488:1528	previously detected structural variations	1488:1528	It was demonstrated that arabinan decomposition is independent of previously detected structural variations.
30333848	2	61	theme	neutral	311:317	arg1	chains					331:336	neutral pectic side chains	311:336	neutral pectic side chains (arabinans and galactans)	311:362	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	1	62	theme	cultivar	196:203	arg1	composition					220:230	both cultivar and structural composition	191:230	both cultivar and structural composition of their pectic polysaccharides	191:262	Physiological and textural properties of apples are greatly influenced by both cultivar and structural composition of their pectic polysaccharides.
30333848	12	63	theme	decreased	1773:1781	arg1	portions					1783:1790	decreased portions	1773:1790	decreased portions of galactan-bound, terminal α-arabinopyranose units	1773:1842	Analysis of endo-galactanase hydrolysates showed decreased portions of galactan-bound, terminal α-arabinopyranose units after storage.
30333848	7	64	theme	enzymatic	1099:1107	arg1	approaches					1119:1128	enzymatic profiling approaches	1099:1128	enzymatic profiling approaches	1099:1128	By using enzymatic profiling approaches, rare structural elements such as β-arabinofuranose and α-arabinopyranose residues were detected.
30333848	5	65	theme	enzymatic	872:880	arg1	cleavage					882:889	enzymatic cleavage	872:889	enzymatic cleavage	872:889	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	6	66	theme	different	987:995	arg1	arabinans					1014:1022	Structurally different, highly branched arabinans	974:1022	Structurally different, highly branched arabinans	974:1022	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	6	67	dep	different	987:995	arg1	branched					1005:1012	branched	1005:1012	branched	1005:1012	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	14	68	dep	demonstrate	1978:1988	arg1	prone					2102:2106	prone	2102:2106	prone	2102:2106	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	3	69	theme	neighboring	585:595	arg1	residues					597:604	neighboring residues	585:604	neighboring residues	585:604	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	5	70	theme	neutral	942:948	arg1	chains					955:960	the neutral side chains	938:960	the neutral side chains of pectins	938:971	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	11	71	theme	side	1633:1636	arg1	chains					1638:1643	β-arabinofuranose containing side chains	1604:1643	β-arabinofuranose containing side chains	1604:1643	In addition, analysis of endo-arabinanase hydrolysates demonstrated that β-arabinofuranose containing side chains are enriched after storage and may play a major role in postharvest processes.
30333848	11	72	theme	β-arabinofuranose	1604:1620	arg1	chains					1638:1643	β-arabinofuranose containing side chains	1604:1643	β-arabinofuranose containing side chains	1604:1643	In addition, analysis of endo-arabinanase hydrolysates demonstrated that β-arabinofuranose containing side chains are enriched after storage and may play a major role in postharvest processes.
30333848	0	73	theme	Apple	70:74	arg1	Cultivars					76:84	14 Apple Cultivars	67:84	14 Apple Cultivars	67:84	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	9	74	theme	Cold	1355:1358	arg1	storage					1360:1366	Cold storage	1355:1366	Cold storage	1355:1366	Cold storage resulted in decreased portions of branched arabinans.
30333848	5	75	theme	detailed	914:921	arg1	information					923:933	detailed information	914:933	detailed information on the neutral side chains of pectins	914:971	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	4	76	theme	arabinans	697:705	arg1	structures					683:692	fine structures	678:692	fine structures of arabinans and galactans	678:719	Therefore, fine structures of arabinans and galactans were analyzed in 14 apple cultivars before and after storage.
30333848	1	77	theme	apples	158:163	arg1	properties					144:153	Physiological and textural properties	117:153	Physiological and textural properties of apples	117:163	Physiological and textural properties of apples are greatly influenced by both cultivar and structural composition of their pectic polysaccharides.
30333848	4	78	theme	galactans	711:719	arg1	structures					683:692	fine structures	678:692	fine structures of arabinans and galactans	678:719	Therefore, fine structures of arabinans and galactans were analyzed in 14 apple cultivars before and after storage.
30333848	9	79	theme	decreased	1380:1388	arg1	portions					1390:1397	decreased portions	1380:1397	decreased portions of branched arabinans	1380:1419	Cold storage resulted in decreased portions of branched arabinans.
30333848	6	80	theme	linear	1028:1033	arg1	galactans					1048:1056	linear β-1,4-linked galactans	1028:1056	linear β-1,4-linked galactans	1028:1056	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	5	81	from	information	923:933	arg1	chains					955:960	the neutral side chains	938:960	the neutral side chains of pectins	938:971	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	0	82	theme	Structural	9:18	arg1	Characterization					20:35	Detailed Structural Characterization	0:35	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.	0:115	Detailed Structural Characterization of Arabinans and Galactans of 14 Apple Cultivars Before and After Cold Storage.
30333848	9	83	theme	arabinans	1411:1419	arg1	portions					1390:1397	decreased portions	1380:1397	decreased portions of branched arabinans	1380:1419	Cold storage resulted in decreased portions of branched arabinans.
30333848	5	84	theme	pectins	965:971	arg1	chains					955:960	the neutral side chains	938:960	the neutral side chains of pectins	938:971	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	12	85	theme	units	1838:1842	arg1	portions					1783:1790	decreased portions	1773:1790	decreased portions of galactan-bound, terminal α-arabinopyranose units	1773:1842	Analysis of endo-galactanase hydrolysates showed decreased portions of galactan-bound, terminal α-arabinopyranose units after storage.
30333848	2	86	dep	chains	331:336	arg1	arabinans					339:347	arabinans	339:347	arabinans	339:347	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	2	86	dep	chains	331:336	arg1	galactans					353:361	galactans	353:361	galactans	353:361	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	2	87	theme	major	371:375	arg1	role					377:380	a major role	369:380	a major role	369:380	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	5	88	theme	profiling	842:850	arg1	approaches					852:861	profiling approaches	842:861	profiling approaches based on enzymatic cleavage	842:889	Besides conventional methods such as methylation analysis, profiling approaches based on enzymatic cleavage were applied to obtain detailed information on the neutral side chains of pectins.
30333848	14	89	theme	high	1994:1997	arg1	complexity					1999:2008	the high complexity	1990:2008	the high complexity of neutral pectin side chains in apples and that pectic structural elements	1990:2084	The results of this study demonstrate the high complexity of neutral pectin side chains in apples and that pectic structural elements are differently prone to postharvest modifications.
30333848	6	90	located	detected	1063:1070	arg2	arabinans					1014:1022	Structurally different, highly branched arabinans	974:1022	Structurally different, highly branched arabinans	974:1022	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	6	90	located	detected	1063:1070	arg1	cultivars					1079:1087	all cultivars	1075:1087	all cultivars	1075:1087	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	6	90	located	detected	1063:1070	arg2	galactans					1048:1056	linear β-1,4-linked galactans	1028:1056	linear β-1,4-linked galactans	1028:1056	Structurally different, highly branched arabinans and linear β-1,4-linked galactans were detected in all cultivars.
30333848	11	91	theme	endo-arabinanase	1556:1571	arg1	hydrolysates					1573:1584	endo-arabinanase hydrolysates	1556:1584	endo-arabinanase hydrolysates	1556:1584	In addition, analysis of endo-arabinanase hydrolysates demonstrated that β-arabinofuranose containing side chains are enriched after storage and may play a major role in postharvest processes.
30333848	2	92	theme	postharvest	411:421	arg1	processes					423:431	postharvest processes	411:431	postharvest processes	411:431	In previous studies, it was demonstrated that neutral pectic side chains (arabinans and galactans) play a major role during fruit development and postharvest processes.
30333848	1	93	theme	structural	209:218	arg1	composition					220:230	both cultivar and structural composition	191:230	both cultivar and structural composition of their pectic polysaccharides	191:262	Physiological and textural properties of apples are greatly influenced by both cultivar and structural composition of their pectic polysaccharides.
30333848	12	94	theme	galactan-bound	1795:1808	arg1	units					1838:1842	galactan-bound, terminal α-arabinopyranose units	1795:1842	galactan-bound, terminal α-arabinopyranose units	1795:1842	Analysis of endo-galactanase hydrolysates showed decreased portions of galactan-bound, terminal α-arabinopyranose units after storage.
30333848	3	95	theme	analytical	647:656	arg1	methods					658:664	conventional analytical methods	634:664	conventional analytical methods	634:664	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	3	96	theme	structural	478:487	arg1	heterogeneity					489:501	a high structural heterogeneity	471:501	a high structural heterogeneity	471:501	However, these complex polymers have a high structural heterogeneity, and some structural elements such as side chain substituents and substitution of neighboring residues cannot be analyzed by using conventional analytical methods.
30333848	10	97	theme	arabinan	1447:1454	arg1	decomposition					1456:1468	arabinan decomposition	1447:1468	arabinan decomposition	1447:1468	It was demonstrated that arabinan decomposition is independent of previously detected structural variations.
30333848	1	98	theme	polysaccharides	248:262	arg1	composition					220:230	both cultivar and structural composition	191:230	both cultivar and structural composition of their pectic polysaccharides	191:262	Physiological and textural properties of apples are greatly influenced by both cultivar and structural composition of their pectic polysaccharides.
32172531	4	0	theme	glycosylated	616:627	arg1	channels					634:641	normal glycosylated hERG channels	609:641	normal glycosylated hERG channels	609:641	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	4	1	gly	glycosylated	616:627	arg1	channels					634:641	normal glycosylated hERG channels	609:641	normal glycosylated hERG channels	609:641	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	1	2	theme	channel	156:162	arg1	hERG					164:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	3	3	theme	S5-pore	491:497	arg1	linker					499:504	the S5-pore linker	487:504	the S5-pore linker of hERG	487:512	The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, protects hERG from such cleavage.
32172531	0	4	theme	proteolytic	76:86	arg1	susceptibility					88:101	proteolytic susceptibility	76:101	proteolytic susceptibility	76:101	Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	7	5	attach	present	1182:1188	arg1	medium					1197:1202	the medium	1193:1202	the medium of human embryonic kidney cells	1193:1234	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	7	5	attach	present	1182:1188	arg2	CAPN					1166:1169	CAPN	1166:1169	CAPN	1166:1169	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	9	6	link	N-linked	1383:1390	arg1	glycosylation					1392:1404	N-linked glycosylation	1383:1404	N-linked glycosylation	1383:1404	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	4	7	theme	normal	609:614	arg1	channels					634:641	normal glycosylated hERG channels	609:641	normal glycosylated hERG channels	609:641	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	1	8	theme	long	253:256	arg1	linker					266:271	the unusually long S5-pore linker	239:271	the unusually long S5-pore linker of the channel	239:286	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	10	9	theme	M.	1542:1543	arg1	Glycosylation					1596:1608	- Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation	1528:1608	- Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation	1528:1608	- Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	7	10	theme	normal	1055:1060	arg1	channels					1075:1082	normal glycosylated channels	1055:1082	normal glycosylated channels	1055:1082	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	10	11	theme	hERG	1621:1624	arg1	channels					1626:1633	hERG channels	1621:1633	hERG channels on the plasma membrane	1621:1656	- Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	9	12	theme	plasma	1512:1517	arg1	membrane					1519:1526	the plasma membrane	1508:1526	the plasma membrane	1508:1526	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	8	13	theme	hERG	1331:1334	arg1	current					1336:1342	nonglycosylated hERG current	1315:1342	nonglycosylated hERG current	1315:1342	Inhibition of CAPN resulted in an increase of nonglycosylated hERG current.
32172531	1	14	theme	S5-pore	258:264	arg1	linker					266:271	the unusually long S5-pore linker	239:271	the unusually long S5-pore linker of the channel	239:286	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	5	15	from	PK-cleavage	801:811	arg1	hERG					791:794	hERG	791:794	hERG from PK-cleavage	791:811	Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited.
32172531	9	16	theme	hERG	1482:1485	arg1	stability					1495:1503	hERG channel stability	1482:1503	hERG channel stability	1482:1503	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	1	17	gly	glycosylation	188:200	arg1	position					205:212	position 598	205:216	position 598	205:216	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	1	17	gly	glycosylation	188:200	arg1	hERG					164:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	7	18	from	medium	1197:1202	arg1	present					1182:1188	present	1182:1188	present	1182:1188	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	3	19	theme	toxin	458:462	arg1	BeKm-1					464:469	The scorpion toxin BeKm-1	445:469	The scorpion toxin BeKm-1	445:469	The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, protects hERG from such cleavage.
32172531	8	20	theme	CAPN	1283:1286	arg1	Inhibition					1269:1278	Inhibition	1269:1278	Inhibition of CAPN	1269:1286	Inhibition of CAPN resulted in an increase of nonglycosylated hERG current.
32172531	5	21	theme	hERG	844:847	arg1	glycosylation					827:839	glycosylation	827:839	glycosylation of hERG	827:847	Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited.
32172531	9	22	theme	protease-mediated	1428:1444	arg1	degradation					1446:1456	protease-mediated degradation	1428:1456	protease-mediated degradation	1428:1456	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	6	23	theme	PK	1028:1029	arg1	cleavage					1031:1038	PK cleavage	1028:1038	PK cleavage	1028:1038	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	7	24	theme	hERG	1101:1104	arg1	channels					1106:1113	nonglycosylated hERG channels	1085:1113	nonglycosylated hERG channels	1085:1113	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	8	25	gly	nonglycosylated	1315:1329	arg1	current					1336:1342	nonglycosylated hERG current	1315:1342	nonglycosylated hERG current	1315:1342	Inhibition of CAPN resulted in an increase of nonglycosylated hERG current.
32172531	6	26	theme	PK	946:947	arg1	cleavage					949:956	PK cleavage	946:956	PK cleavage	946:956	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	1	27	theme	N-linked	179:186	arg1	glycosylation					188:200	N-linked glycosylation	179:200	N-linked glycosylation	179:200	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	7	28	from	present	1182:1188	arg1	medium					1197:1202	the medium	1193:1202	the medium of human embryonic kidney cells	1193:1234	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	10	29	theme	proteolytic	1672:1682	arg1	susceptibility					1684:1697	proteolytic susceptibility	1672:1697	proteolytic susceptibility	1672:1697	- Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	3	30	theme	hERG	509:512	arg1	linker					499:504	the S5-pore linker	487:504	the S5-pore linker of hERG	487:512	The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, protects hERG from such cleavage.
32172531	1	31	link	N-linked	179:186	arg1	glycosylation					188:200	N-linked glycosylation	179:200	N-linked glycosylation	179:200	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	10	32	from	channels	1626:1633	arg1	membrane					1649:1656	the plasma membrane	1638:1656	the plasma membrane	1638:1656	- Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	4	33	theme	hERG	660:663	arg1	channels					665:672	nonglycosylated hERG channels	644:672	nonglycosylated hERG channels	644:672	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	2	34	theme	proteolytic	361:371	arg1	cleavage					373:380	proteolytic cleavage	361:380	proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN)	361:442	In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN).
32172531	7	35	theme	glycosylated	1062:1073	arg1	channels					1075:1082	normal glycosylated channels	1055:1082	normal glycosylated channels	1055:1082	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	5	36	gly	glycosylation	827:839	arg1	hERG					844:847	hERG	844:847	hERG	844:847	Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited.
32172531	2	37	theme	other	292:296	arg1	work					298:301	other work	292:301	other work	292:301	In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN).
32172531	7	38	theme	culture	1249:1255	arg1	conditions					1257:1266	normal culture conditions	1242:1266	normal culture conditions	1242:1266	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	0	39	theme	hERG	25:28	arg1	channels					30:37	hERG channels	25:37	hERG channels	25:37	Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	1	40	theme	channel	280:286	arg1	linker					266:271	the unusually long S5-pore linker	239:271	the unusually long S5-pore linker of the channel	239:286	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	1	41	from	linker	266:271	arg1	located					228:234	located	228:234	located	228:234	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	9	42	gly	glycosylation	1392:1404	arg1	hERG					1482:1485	hERG channel stability	1482:1503	hERG channel stability	1482:1503	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	9	42	gly	glycosylation	1392:1404	arg1	channel					1487:1493	hERG channel stability	1482:1503	hERG channel stability	1482:1503	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	1	43	theme	ether-a-go-go	114:126	arg1	hERG					142:145	hERG	142:145	hERG	142:145	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	1	43	theme	ether-a-go-go	114:126	arg1	gene					136:139	The human ether-a-go-go related gene	104:139	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	10	44	theme	plasma	1642:1647	arg1	membrane					1649:1656	the plasma membrane	1638:1656	the plasma membrane	1638:1656	- Lamothe, S. M., Hulbert, M., Guo, J., Li, W., Yang, T., Zhang, S. Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	4	45	theme	present	556:562	arg1	study					564:568	the present study	552:568	the present study	552:568	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	3	46	theme	scorpion	449:456	arg1	BeKm-1					464:469	The scorpion toxin BeKm-1	445:469	The scorpion toxin BeKm-1	445:469	The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, protects hERG from such cleavage.
32172531	6	47	theme	glycosylation	977:989	arg1	inhibition					963:972	inhibition	963:972	inhibition of glycosylation	963:989	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	1	48	located	located	228:234	arg2	position					205:212	position 598	205:216	position 598	205:216	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	1	48	located	located	228:234	arg1	linker					266:271	the unusually long S5-pore linker	239:271	the unusually long S5-pore linker of the channel	239:286	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	5	49	theme	BeKm-1	781:786	arg1	effect					771:776	the protective effect	756:776	the protective effect of BeKm-1 on hERG from PK-cleavage	756:811	Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited.
32172531	9	50	theme	N-linked	1383:1390	arg1	glycosylation					1392:1404	N-linked glycosylation	1383:1404	N-linked glycosylation	1383:1404	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	6	51	theme	hERG	898:901	arg1	S620T					912:916	S620T	912:916	S620T	912:916	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	51	theme	hERG	898:901	arg1	resistant					933:941	resistant	933:941	resistant	933:941	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	51	theme	hERG	898:901	arg1	channels					903:910	The inactivation-deficient mutant hERG channels	864:910	The inactivation-deficient mutant hERG channels S620T and S631A	864:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	51	theme	hERG	898:901	arg1	S631A					922:926	S631A	922:926	S631A	922:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	4	52	gly	nonglycosylated	644:658	arg1	channels					665:672	nonglycosylated hERG channels	644:672	nonglycosylated hERG channels	644:672	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	3	53	theme	such	534:537	arg1	cleavage					539:546	such cleavage	534:546	such cleavage	534:546	The scorpion toxin BeKm-1, which binds to the S5-pore linker of hERG, protects hERG from such cleavage.
32172531	2	54	theme	S5-pore	389:395	arg1	linker					397:402	the S5-pore linker	385:402	the S5-pore linker	385:402	In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN).
32172531	7	55	theme	nonglycosylated	1085:1099	arg1	channels					1106:1113	nonglycosylated hERG channels	1085:1113	nonglycosylated hERG channels	1085:1113	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	6	56	theme	mutant	891:896	arg1	S620T					912:916	S620T	912:916	S620T	912:916	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	56	theme	mutant	891:896	arg1	resistant					933:941	resistant	933:941	resistant	933:941	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	56	theme	mutant	891:896	arg1	channels					903:910	The inactivation-deficient mutant hERG channels	864:910	The inactivation-deficient mutant hERG channels S620T and S631A	864:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	56	theme	mutant	891:896	arg1	S631A					922:926	S631A	922:926	S631A	922:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	8	57	theme	nonglycosylated	1315:1329	arg1	current					1336:1342	nonglycosylated hERG current	1315:1342	nonglycosylated hERG current	1315:1342	Inhibition of CAPN resulted in an increase of nonglycosylated hERG current.
32172531	7	58	theme	kidney	1223:1228	arg1	cells					1230:1234	human embryonic kidney cells	1207:1234	human embryonic kidney cells	1207:1234	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	2	59	dep	proteinase	407:416	arg1	PK					421:422	PK	421:422	PK	421:422	In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN).
32172531	2	59	dep	proteinase	407:416	arg1	K					418:418	K	418:418	proteinase K (PK)	407:423	In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN).
32172531	1	60	theme	related	128:134	arg1	hERG					142:145	hERG	142:145	hERG	142:145	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	1	60	theme	related	128:134	arg1	gene					136:139	The human ether-a-go-go related gene	104:139	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	0	61	theme	plasma	46:51	arg1	membrane					53:60	the plasma membrane	42:60	the plasma membrane	42:60	Glycosylation stabilizes hERG channels on the plasma membrane by decreasing proteolytic susceptibility.
32172531	6	62	theme	inactivation-deficient	868:889	arg1	S620T					912:916	S620T	912:916	S620T	912:916	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	62	theme	inactivation-deficient	868:889	arg1	resistant					933:941	resistant	933:941	resistant	933:941	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	62	theme	inactivation-deficient	868:889	arg1	channels					903:910	The inactivation-deficient mutant hERG channels	864:910	The inactivation-deficient mutant hERG channels S620T and S631A	864:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	62	theme	inactivation-deficient	868:889	arg1	S631A					922:926	S631A	922:926	S631A	922:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	7	63	gly	nonglycosylated	1085:1099	arg1	channels					1106:1113	nonglycosylated hERG channels	1085:1113	nonglycosylated hERG channels	1085:1113	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	5	64	from	effect	771:776	arg1	hERG					791:794	hERG	791:794	hERG from PK-cleavage	791:811	Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited.
32172531	1	65	theme	gene	136:139	arg1	hERG					164:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	6	66	dep	channels	903:910	arg1	S620T					912:916	S620T	912:916	S620T	912:916	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	66	dep	channels	903:910	arg1	channels					903:910	The inactivation-deficient mutant hERG channels	864:910	The inactivation-deficient mutant hERG channels S620T and S631A	864:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	6	66	dep	channels	903:910	arg1	S631A					922:926	S631A	922:926	S631A	922:926	The inactivation-deficient mutant hERG channels S620T and S631A were resistant to PK cleavage, and inhibition of glycosylation rendered both mutants susceptible to PK cleavage.
32172531	4	67	theme	extracellular	725:737	arg1	PK					739:740	extracellular PK	725:740	extracellular PK	725:740	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	4	68	theme	nonglycosylated	644:658	arg1	channels					665:672	nonglycosylated hERG channels	644:672	nonglycosylated hERG channels	644:672	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
32172531	1	69	theme	human	108:112	arg1	hERG					142:145	hERG	142:145	hERG	142:145	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	1	69	theme	human	108:112	arg1	gene					136:139	The human ether-a-go-go related gene	104:139	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	1	70	from	located	228:234	arg1	linker					266:271	the unusually long S5-pore linker	239:271	the unusually long S5-pore linker of the channel	239:286	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	7	71	theme	cells	1230:1234	arg1	medium					1197:1202	the medium	1193:1202	the medium of human embryonic kidney cells	1193:1234	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	2	72	from	linker	397:402	arg1	cleavage					373:380	proteolytic cleavage	361:380	proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN)	361:442	In other work we have demonstrated that hERG is uniquely susceptible to proteolytic cleavage at the S5-pore linker by proteinase K (PK) and calpain (CAPN).
32172531	7	73	theme	embryonic	1213:1221	arg1	cells					1230:1234	human embryonic kidney cells	1207:1234	human embryonic kidney cells	1207:1234	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	7	74	gly	glycosylated	1062:1073	arg1	channels					1075:1082	normal glycosylated channels	1055:1082	normal glycosylated channels	1055:1082	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	7	75	theme	human	1207:1211	arg1	cells					1230:1234	human embryonic kidney cells	1207:1234	human embryonic kidney cells	1207:1234	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	7	76	theme	normal	1242:1247	arg1	conditions					1257:1266	normal culture conditions	1242:1266	normal culture conditions	1242:1266	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	9	77	theme	channel	1487:1493	arg1	stability					1495:1503	hERG channel stability	1482:1503	hERG channel stability	1482:1503	In summary, our results revealed that N-linked glycosylation protects hERG against protease-mediated degradation and thus contributes to hERG channel stability on the plasma membrane.
32172531	8	78	theme	current	1336:1342	arg1	increase					1303:1310	an increase	1300:1310	an increase of nonglycosylated hERG current	1300:1342	Inhibition of CAPN resulted in an increase of nonglycosylated hERG current.
32172531	5	79	theme	protective	760:769	arg1	effect					771:776	the protective effect	756:776	the protective effect of BeKm-1 on hERG from PK-cleavage	756:811	Furthermore, the protective effect of BeKm-1 on hERG from PK-cleavage was lost when glycosylation of hERG was inhibited.
32172531	7	80	located	present	1182:1188	arg1	medium					1197:1202	the medium	1193:1202	the medium of human embryonic kidney cells	1193:1234	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	7	80	located	present	1182:1188	arg2	CAPN					1166:1169	CAPN	1166:1169	CAPN	1166:1169	Compared with normal glycosylated channels, nonglycosylated hERG channels were also more susceptible to cleavage mediated by CAPN, which was present in the medium of human embryonic kidney cells under normal culture conditions.
32172531	1	81	theme	-encoded	147:154	arg1	hERG					164:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG	104:167	The human ether-a-go-go related gene (hERG)-encoded channel hERG undergoes N-linked glycosylation at position 598, which is located in the unusually long S5-pore linker of the channel.
32172531	4	82	theme	hERG	629:632	arg1	channels					634:641	normal glycosylated hERG channels	609:641	normal glycosylated hERG channels	609:641	In the present study, our data revealed that, compared with normal glycosylated hERG channels, nonglycosylated hERG channels were significantly more susceptible to cleavage by extracellular PK.
31320925	4	0	theme	sugar	913:917	arg1	release					919:925	maximum sugar release	905:925	maximum sugar release	905:925	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	1	1	theme	cell	285:288	arg1	walls					290:294	cell walls	285:294	cell walls	285:294	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
31320925	9	2	theme	knife	1726:1730	arg1	milling					1732:1738	knife milling	1726:1738	knife milling	1726:1738	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	6	3	theme	hemicellulose	1229:1241	arg1	majority					1217:1224	the majority	1213:1224	the majority of hemicellulose	1213:1241	In general, DSA successfully solubilized hemicellulose, while CELF removed nearly 80% of Klason lignin from switchgrass in addition to the majority of hemicellulose.
31320925	12	4	theme	biological	2279:2288	arg1	processing					2290:2299	biological processing	2279:2299	biological processing of biomass to fuels	2279:2319	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	3	5	theme	overall	589:595	arg1	cost					605:608	the overall capital cost	585:608	the overall capital cost	585:608	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	7	6	from	impact	1310:1315	arg1	compositions					1328:1339	biomass compositions	1320:1339	biomass compositions	1320:1339	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	12	7	theme	particle	2197:2204	arg1	reduction					2211:2219	particle size reduction	2197:2219	particle size reduction prior to pretreatment	2197:2241	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	11	8	theme	pretreated	2073:2082	arg1	solids					2096:2101	pretreated switchgrass solids	2073:2101	pretreated switchgrass solids	2073:2101	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	11	9	from	hydrolysis	2059:2068	arg1	yields					2037:2042	nearly theoretical sugar yields	2012:2042	nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids	2012:2101	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	4	10	theme	enzymatic	972:980	arg1	hydrolysis					982:991	subsequent enzymatic hydrolysis	961:991	subsequent enzymatic hydrolysis	961:991	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	11	theme	reduction	662:670	arg1	effect					638:643	the effect	634:643	the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass	634:736	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	11	12	theme	size	2111:2114	arg1	reduction					2116:2124	size reduction	2111:2124	size reduction	2111:2124	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	1	13	theme	natural	224:230	arg1	recalcitrance					232:244	the natural recalcitrance	220:244	the natural recalcitrance of plant biomass so polysaccharides in cell walls	220:294	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
31320925	9	14	theme	adequate	1770:1777	arg1	yields					1785:1790	adequate sugar yields	1770:1790	adequate sugar yields	1770:1790	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	8	15	theme	unsoaked	1509:1516	arg1	samples					1518:1524	unsoaked samples	1509:1524	unsoaked samples	1509:1524	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	4	16	theme	biomass	676:682	arg1	presoaking					684:693	biomass presoaking	676:693	biomass presoaking	676:693	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	0	17	theme	sulfuric	143:150	arg1	acid					152:155	dilute sulfuric acid	136:155	dilute sulfuric acid pretreatment	136:168	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	11	18	theme	sugar	2031:2035	arg1	yields					2037:2042	nearly theoretical sugar yields	2012:2042	nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids	2012:2101	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	1	19	from	recalcitrance	232:244	arg1	walls					290:294	cell walls	285:294	cell walls	285:294	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
31320925	12	20	theme	prior	2221:2225	arg1	reduction					2211:2219	particle size reduction	2197:2219	particle size reduction prior to pretreatment	2197:2241	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	8	21	dep	18 h	1635:1638	arg1	to					1632:1633	to	1632:1633	to	1632:1633	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	9	22	theme	subsequent	1795:1804	arg1	hydrolysis					1816:1825	subsequent enzymatic hydrolysis	1795:1825	subsequent enzymatic hydrolysis	1795:1825	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	8	23	theme	sugar	1535:1539	arg1	yields					1541:1546	sugar yields	1535:1546	sugar yields from enzymatic hydrolysis of CELF solids	1535:1587	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	10	24	from	solids	1833:1838	arg1	hand					1854:1857	the other hand	1844:1857	the other hand	1844:1857	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	4	25	theme	Alamo	720:724	arg1	switchgrass					726:736	Alamo switchgrass	720:736	Alamo switchgrass	720:736	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	10	26	theme	identical	1876:1884	arg1	yields					1892:1897	nearly identical sugar yields	1869:1897	nearly identical sugar yields	1869:1897	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	0	27	theme	maximum	87:93	arg1	recovery					101:108	maximum sugar recovery	87:108	maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment	87:168	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	8	28	theme	CELF	1577:1580	arg1	solids					1582:1587	CELF solids	1577:1587	CELF solids	1577:1587	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	7	29	theme	size	1268:1271	arg1	reduction					1273:1281	particle size reduction	1259:1281	particle size reduction	1259:1281	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	4	30	theme	sulfuric	783:790	arg1	DSA					798:800	DSA	798:800	DSA	798:800	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	30	theme	sulfuric	783:790	arg1	acid					792:795	dilute sulfuric acid	776:795	dilute sulfuric acid (DSA)	776:801	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	7	31	theme	particle	1259:1266	arg1	reduction					1273:1281	particle size reduction	1259:1281	particle size reduction	1259:1281	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	10	32	theme	CELF	1828:1831	arg1	solids					1833:1838	CELF solids	1828:1838	CELF solids	1828:1838	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	0	33	theme	Alamo	113:117	arg1	switchgrass					119:129	Alamo switchgrass	113:129	Alamo switchgrass	113:129	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	4	34	theme	dilute	776:781	arg1	DSA					798:800	DSA	798:800	DSA	798:800	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	34	theme	dilute	776:781	arg1	acid					792:795	dilute sulfuric acid	776:795	dilute sulfuric acid (DSA)	776:801	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	11	35	theme	solids	2096:2101	arg1	hydrolysis					2059:2068	enzymatic hydrolysis	2049:2068	enzymatic hydrolysis of pretreated switchgrass solids	2049:2101	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	2	36	theme	sugar	469:473	arg1	yields					475:480	high sugar yields	464:480	high sugar yields	464:480	Furthermore, lignocellulosic biomass must typically be reduced in size to increase the pretreatment effectiveness and realize high sugar yields.
31320925	3	37	theme	biomass	492:498	arg1	operation					542:550	a very energy-intensive operation	518:550	a very energy-intensive operation	518:550	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	3	37	theme	biomass	492:498	arg1	reduction					505:513	biomass size reduction	492:513	biomass size reduction	492:513	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	8	38	from	hydrolysis	1563:1572	arg1	yields					1541:1546	sugar yields	1535:1546	sugar yields from enzymatic hydrolysis of CELF solids	1535:1587	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	5	39	theme	enzymatic	1010:1018	arg1	hydrolysis					1020:1029	enzymatic hydrolysis	1010:1029	enzymatic hydrolysis	1010:1029	Sugar yields by enzymatic hydrolysis were measured over a range of enzyme loadings.
31320925	10	40	theme	milled	1917:1922	arg1	switchgrass					1924:1934	unmilled and milled switchgrass	1904:1934	unmilled and milled switchgrass	1904:1934	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	8	41	theme	enzymatic	1446:1454	arg1	hydrolysis					1456:1465	enzymatic hydrolysis	1446:1465	enzymatic hydrolysis of DSA-pretreated switchgrass	1446:1495	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	9	42	theme	particular	1663:1672	arg1	importance					1674:1683	particular importance	1663:1683	particular importance	1663:1683	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	10	43	theme	unmilled	1904:1911	arg1	switchgrass					1924:1934	unmilled and milled switchgrass	1904:1934	unmilled and milled switchgrass	1904:1934	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	6	44	theme	lignin	1174:1179	arg1	%					1162:1162	nearly 80%	1153:1162	nearly 80% of Klason lignin	1153:1179	In general, DSA successfully solubilized hemicellulose, while CELF removed nearly 80% of Klason lignin from switchgrass in addition to the majority of hemicellulose.
31320925	6	44	theme	lignin	1174:1179	arg1	lignin					1174:1179	Klason lignin	1167:1179	Klason lignin	1167:1179	In general, DSA successfully solubilized hemicellulose, while CELF removed nearly 80% of Klason lignin from switchgrass in addition to the majority of hemicellulose.
31320925	8	45	theme	time	1654:1657	arg1	18 h					1635:1638	18 h	1635:1638	18 h	1635:1638	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	8	45	theme	time	1654:1657	arg1	time					1654:1657	presoaking time	1643:1657	presoaking time	1643:1657	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	8	46	theme	switchgrass	1485:1495	arg1	hydrolysis					1456:1465	enzymatic hydrolysis	1446:1465	enzymatic hydrolysis of DSA-pretreated switchgrass	1446:1495	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	2	47	theme	lignocellulosic	351:365	arg1	biomass					367:373	lignocellulosic biomass	351:373	lignocellulosic biomass	351:373	Furthermore, lignocellulosic biomass must typically be reduced in size to increase the pretreatment effectiveness and realize high sugar yields.
31320925	1	48	theme	plant	249:253	arg1	polysaccharides					266:280	plant biomass so polysaccharides	249:280	plant biomass so polysaccharides	249:280	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
31320925	13	49	theme	enzyme	2416:2421	arg1	loadings					2423:2430	low enzyme loadings	2412:2430	low enzyme loadings	2412:2430	In addition, presoaking proved much more effective for CELF than for DSA, particularly at low enzyme loadings.
31320925	12	50	theme	processing	2290:2299	arg1	costs					2270:2274	overall costs	2262:2274	overall costs of biological processing of biomass to fuels	2262:2319	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	7	51	theme	biomass	1320:1326	arg1	compositions					1328:1339	biomass compositions	1320:1339	biomass compositions	1320:1339	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	1	52	theme	so	263:264	arg1	polysaccharides					266:280	plant biomass so polysaccharides	249:280	plant biomass so polysaccharides	249:280	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
31320925	5	53	theme	enzyme	1061:1066	arg1	loadings					1068:1075	enzyme loadings	1061:1075	enzyme loadings	1061:1075	Sugar yields by enzymatic hydrolysis were measured over a range of enzyme loadings.
31320925	4	54	from	effect	638:643	arg1	deconstruction					702:715	the deconstruction	698:715	the deconstruction of Alamo switchgrass	698:736	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	3	55	theme	energy-intensive	525:540	arg1	operation					542:550	a very energy-intensive operation	518:550	a very energy-intensive operation	518:550	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	3	55	theme	energy-intensive	525:540	arg1	reduction					505:513	biomass size reduction	492:513	biomass size reduction	492:513	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	4	56	theme	maximum	905:911	arg1	release					919:925	maximum sugar release	905:925	maximum sugar release	905:925	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	10	57	theme	enzyme	1953:1958	arg1	loadings					1960:1967	very low enzyme loadings	1944:1967	very low enzyme loadings	1944:1967	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	11	58	theme	switchgrass	2084:2094	arg1	solids					2096:2101	pretreated switchgrass solids	2073:2101	pretreated switchgrass solids	2073:2101	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	4	59	theme	pretreatment	867:878	arg1	conditions					880:889	pretreatment conditions	867:889	pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis	867:991	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	60	theme	presoaking	684:693	arg1	effect					638:643	the effect	634:643	the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass	634:736	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	10	61	theme	other	1848:1852	arg1	hand					1854:1857	the other hand	1844:1857	the other hand	1844:1857	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	8	62	dep	increased	1420:1428	arg1	whereas					1527:1533	whereas	1527:1533	whereas	1527:1533	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	12	63	theme	size	2206:2209	arg1	reduction					2211:2219	particle size reduction	2197:2219	particle size reduction prior to pretreatment	2197:2241	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	0	64	theme	dilute	136:141	arg1	acid					152:155	dilute sulfuric acid	136:155	dilute sulfuric acid pretreatment	136:168	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	3	65	theme	capital	597:603	arg1	cost					605:608	the overall capital cost	585:608	the overall capital cost	585:608	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	4	66	theme	subsequent	961:970	arg1	hydrolysis					982:991	subsequent enzymatic hydrolysis	961:991	subsequent enzymatic hydrolysis	961:991	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	67	theme	size	657:660	arg1	reduction					662:670	particle size reduction	648:670	particle size reduction	648:670	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	0	68	theme	acid	152:155	arg1	pretreatment					157:168	dilute sulfuric acid pretreatment	136:168	dilute sulfuric acid pretreatment	136:168	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	11	69	theme	theoretical	2019:2029	arg1	yields					2037:2042	nearly theoretical sugar yields	2012:2042	nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids	2012:2101	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	9	70	theme	sugar	1779:1783	arg1	yields					1785:1790	adequate sugar yields	1770:1790	adequate sugar yields	1770:1790	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	4	71	theme	Enhanced	818:825	arg1	CELF					858:861	CELF	858:861	CELF	858:861	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	71	theme	Enhanced	818:825	arg1	Fractionation					843:855	Co-solvent Enhanced Lignocellulosic Fractionation	807:855	Co-solvent Enhanced Lignocellulosic Fractionation (CELF)	807:862	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	11	72	theme	enzymatic	2049:2057	arg1	hydrolysis					2059:2068	enzymatic hydrolysis	2049:2068	enzymatic hydrolysis of pretreated switchgrass solids	2049:2101	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	9	73	theme	enzymatic	1806:1814	arg1	hydrolysis					1816:1825	subsequent enzymatic hydrolysis	1795:1825	subsequent enzymatic hydrolysis	1795:1825	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	8	74	theme	enzymatic	1553:1561	arg1	hydrolysis					1563:1572	enzymatic hydrolysis	1553:1572	enzymatic hydrolysis of CELF solids	1553:1587	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	10	75	theme	sugar	1886:1890	arg1	yields					1892:1897	nearly identical sugar yields	1869:1897	nearly identical sugar yields	1869:1897	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	6	76	dep	majority	1217:1224	arg1	addition					1201:1208	addition	1201:1208	addition	1201:1208	In general, DSA successfully solubilized hemicellulose, while CELF removed nearly 80% of Klason lignin from switchgrass in addition to the majority of hemicellulose.
31320925	0	77	theme	sugar	95:99	arg1	recovery					101:108	maximum sugar recovery	87:108	maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment	87:168	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	7	78	contain	have	1291:1294	arg1	reduction					1273:1281	particle size reduction	1259:1281	particle size reduction	1259:1281	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	7	78	contain	have	1291:1294	arg2	impact					1310:1315	a significant impact	1296:1315	a significant impact on biomass compositions	1296:1339	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	7	78	contain	have	1291:1294	arg1	Presoaking					1244:1253	Presoaking	1244:1253	Presoaking	1244:1253	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	1	79	theme	BACKGROUND	171:180	arg1	Pretreatment					182:193	BACKGROUND Pretreatment	171:193	BACKGROUND Pretreatment	171:193	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
31320925	12	80	dep	eliminate	2187:2195	arg1	reduce					2255:2260	reduce	2255:2260	reduce overall costs of biological processing of biomass to fuels	2255:2319	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	8	81	theme	solids	1582:1587	arg1	hydrolysis					1563:1572	enzymatic hydrolysis	1553:1572	enzymatic hydrolysis of CELF solids	1553:1587	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	4	82	theme	switchgrass	726:736	arg1	deconstruction					702:715	the deconstruction	698:715	the deconstruction of Alamo switchgrass	698:736	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	83	theme	Co-solvent	807:816	arg1	CELF					858:861	CELF	858:861	CELF	858:861	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	83	theme	Co-solvent	807:816	arg1	Fractionation					843:855	Co-solvent Enhanced Lignocellulosic Fractionation	807:855	Co-solvent Enhanced Lignocellulosic Fractionation (CELF)	807:862	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	12	84	theme	biomass	2304:2310	arg1	processing					2290:2299	biological processing	2279:2299	biological processing of biomass to fuels	2279:2319	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	0	85	theme	switchgrass	119:129	arg1	recovery					101:108	maximum sugar recovery	87:108	maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment	87:168	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	11	86	theme	CONCLUSIONS	1970:1980	arg1	CELF					1982:1985	CONCLUSIONS CELF	1970:1985	CONCLUSIONS CELF	1970:1985	CONCLUSIONS CELF was capable of achieving nearly theoretical sugar yields from enzymatic hydrolysis of pretreated switchgrass solids without size reduction, unlike DSA.
31320925	5	87	theme	Sugar	994:998	arg1	yields					1000:1005	Sugar yields	994:1005	Sugar yields by enzymatic hydrolysis	994:1029	Sugar yields by enzymatic hydrolysis were measured over a range of enzyme loadings.
31320925	0	88	theme	milling	27:33	arg1	requirements					35:46	milling requirements	27:46	milling requirements	27:46	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	2	89	theme	high	464:467	arg1	yields					475:480	high sugar yields	464:480	high sugar yields	464:480	Furthermore, lignocellulosic biomass must typically be reduced in size to increase the pretreatment effectiveness and realize high sugar yields.
31320925	8	90	theme	sugar	1430:1434	arg1	yields					1436:1441	sugar yields	1430:1441	sugar yields	1430:1441	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	3	91	theme	size	500:503	arg1	operation					542:550	a very energy-intensive operation	518:550	a very energy-intensive operation	518:550	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	3	91	theme	size	500:503	arg1	reduction					505:513	biomass size reduction	492:513	biomass size reduction	492:513	However, biomass size reduction is a very energy-intensive operation and contributes significantly to the overall capital cost.
31320925	5	92	theme	loadings	1068:1075	arg1	range					1052:1056	a range	1050:1056	a range of enzyme loadings	1050:1075	Sugar yields by enzymatic hydrolysis were measured over a range of enzyme loadings.
31320925	8	93	theme	presoaking	1643:1652	arg1	time					1654:1657	presoaking time	1643:1657	presoaking time	1643:1657	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	2	94	theme	pretreatment	425:436	arg1	effectiveness					438:450	the pretreatment effectiveness	421:450	the pretreatment effectiveness	421:450	Furthermore, lignocellulosic biomass must typically be reduced in size to increase the pretreatment effectiveness and realize high sugar yields.
31320925	0	95	theme	soaking	61:67	arg1	effectiveness					69:81	soaking effectiveness	61:81	soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment	61:168	CELF significantly reduces milling requirements and improves soaking effectiveness for maximum sugar recovery of Alamo switchgrass over dilute sulfuric acid pretreatment.
31320925	10	96	theme	low	1949:1951	arg1	loadings					1960:1967	very low enzyme loadings	1944:1967	very low enzyme loadings	1944:1967	CELF solids, on the other hand, realized nearly identical sugar yields from unmilled and milled switchgrass even at very low enzyme loadings.
31320925	12	97	theme	overall	2262:2268	arg1	costs					2270:2274	overall costs	2262:2274	overall costs of biological processing of biomass to fuels	2262:2319	These results indicate that CELF may be able to eliminate particle size reduction prior to pretreatment and thereby reduce overall costs of biological processing of biomass to fuels.
31320925	9	98	theme	size	1708:1711	arg1	reduction					1713:1721	particle size reduction	1699:1721	particle size reduction by knife milling to < 2 mm	1699:1748	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	13	99	theme	low	2412:2414	arg1	loadings					2423:2430	low enzyme loadings	2412:2430	low enzyme loadings	2412:2430	In addition, presoaking proved much more effective for CELF than for DSA, particularly at low enzyme loadings.
31320925	6	100	theme	Klason	1167:1172	arg1	lignin					1174:1179	Klason lignin	1167:1179	Klason lignin	1167:1179	In general, DSA successfully solubilized hemicellulose, while CELF removed nearly 80% of Klason lignin from switchgrass in addition to the majority of hemicellulose.
31320925	8	101	theme	DSA-pretreated	1470:1483	arg1	switchgrass					1485:1495	DSA-pretreated switchgrass	1470:1495	DSA-pretreated switchgrass	1470:1495	However, presoaking for 4 h slightly increased sugar yields by enzymatic hydrolysis of DSA-pretreated switchgrass compared to unsoaked samples, whereas sugar yields from enzymatic hydrolysis of CELF solids continued to increase substantially for up to 18 h of presoaking time.
31320925	1	102	theme	biomass	255:261	arg1	polysaccharides					266:280	plant biomass so polysaccharides	249:280	plant biomass so polysaccharides	249:280	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
31320925	9	103	theme	particle	1699:1706	arg1	reduction					1713:1721	particle size reduction	1699:1721	particle size reduction by knife milling to < 2 mm	1699:1748	Of particular importance, DSA required particle size reduction by knife milling to < 2 mm in order to achieve adequate sugar yields by subsequent enzymatic hydrolysis.
31320925	7	104	theme	significant	1298:1308	arg1	impact					1310:1315	a significant impact	1296:1315	a significant impact on biomass compositions	1296:1339	Presoaking and particle size reduction did not have a significant impact on biomass compositions after pretreatment for both DSA and CELF.
31320925	4	105	theme	particle	648:655	arg1	reduction					662:670	particle size reduction	648:670	particle size reduction	648:670	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	106	theme	Lignocellulosic	827:841	arg1	CELF					858:861	CELF	858:861	CELF	858:861	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	4	106	theme	Lignocellulosic	827:841	arg1	Fractionation					843:855	Co-solvent Enhanced Lignocellulosic Fractionation	807:855	Co-solvent Enhanced Lignocellulosic Fractionation (CELF)	807:862	RESULTS In this study, the effect of particle size reduction and biomass presoaking on the deconstruction of Alamo switchgrass was examined prior to pretreatment by dilute sulfuric acid (DSA) and Co-solvent Enhanced Lignocellulosic Fractionation (CELF) at pretreatment conditions optimized for maximum sugar release by each pretreatment coupled with subsequent enzymatic hydrolysis.
31320925	1	107	theme	polysaccharides	266:280	arg1	recalcitrance					232:244	the natural recalcitrance	220:244	the natural recalcitrance of plant biomass so polysaccharides in cell walls	220:294	BACKGROUND Pretreatment is effective in reducing the natural recalcitrance of plant biomass so polysaccharides in cell walls can be accessed for conversion to sugars.
30850477	6	0	dep	blood	731:735	arg1	cells					755:759	B cells	753:759	B cells	753:759	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	6	1	theme	individuals	775:785	arg1	blood					731:735	peripheral blood	720:735	peripheral blood	720:735	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	6	1	theme	individuals	775:785	arg1	marrow					746:751	bone marrow	741:751	bone marrow	741:751	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	2	2	theme	Ab	264:265	arg1	stability					267:275	Ab stability	264:275	Ab stability	264:275	Among others, these N-linked glycans can affect Ag binding and Ab stability.
30850477	12	3	theme	TH2-like	1693:1700	arg1	responses					1711:1719	TH2-like IgG4/IgE responses	1693:1719	TH2-like IgG4/IgE responses	1693:1719	Elevated Fab glycosylation represents an additional hallmark of TH2-like IgG4/IgE responses.
30850477	5	4	theme	B	611:611	arg1	subsets					618:624	B cell subsets	611:624	B cell subsets	611:624	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	11	5	theme	acquisition	1489:1499	arg1	pressure					1456:1463	a differential selection pressure	1431:1463	a differential selection pressure of N-glycosylation site acquisition	1431:1499	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	6	6	theme	erythematosus	845:857	arg1	patients					859:866	six systemic lupus erythematosus patients	826:866	six systemic lupus erythematosus patients	826:866	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	11	7	theme	N-glycosylation	1468:1482	arg1	acquisition					1489:1499	N-glycosylation site acquisition	1468:1499	N-glycosylation site acquisition	1468:1499	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	1	8	theme	B	183:183	arg1	responses					190:198	Ag-specific B cell responses	171:198	Ag-specific B cell responses	171:198	Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses.
30850477	5	9	theme	Ab	578:579	arg1	regions					583:589	Ab V regions	578:589	Ab V regions of naive and memory B cell subsets	578:624	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	4	10	theme	Basic	386:390	arg1	knowledge					392:400	Basic knowledge	386:400	Basic knowledge about patterns of V region glycosylation at different stages of B cell development	386:483	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	4	11	from	stages	456:461	arg1	knowledge					392:400	Basic knowledge	386:400	Basic knowledge about patterns of V region glycosylation at different stages of B cell development	386:483	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	7	12	theme	L	988:988	arg1	chains					990:995	both H and L chains	977:995	chains	990:995	N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients.
30850477	8	13	theme	H	1178:1178	arg1	chain					1180:1184	the H chain	1174:1184	the H chain	1174:1184	No evidence was found for an overall selection bias against acquiring an N-glycosylation site, except for the CDR3 of the H chain.
30850477	3	14	theme	N-linked	287:294	arg1	glycosylation					296:308	Elevated N-linked glycosylation	278:308	Elevated N-linked glycosylation	278:308	Elevated N-linked glycosylation has furthermore been associated with several B cell-associated pathologies.
30850477	4	15	theme	B	466:466	arg1	development					473:483	B cell development	466:483	B cell development	466:483	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	7	16	theme	H	982:982	arg1	chains					990:995	both H and L chains	977:995	chains	990:995	N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients.
30850477	4	17	theme	region	422:427	arg1	glycosylation					429:441	V region glycosylation	420:441	V region glycosylation	420:441	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	5	18	theme	current	511:517	arg1	study					519:523	the current study	507:523	the current study	507:523	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	1	19	theme	N-linked	128:135	arg1	glycans					137:143	N-linked glycans	128:143	N-linked glycans in their V regions	128:162	Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses.
30850477	12	20	theme	Fab	1638:1640	arg1	glycosylation					1642:1654	Elevated Fab glycosylation	1629:1654	Elevated Fab glycosylation	1629:1654	Elevated Fab glycosylation represents an additional hallmark of TH2-like IgG4/IgE responses.
30850477	2	21	link	N-linked	221:228	arg1	glycans					230:236	these N-linked glycans	215:236	these N-linked glycans	215:236	Among others, these N-linked glycans can affect Ag binding and Ab stability.
30850477	0	22	theme	Antibody	68:75	arg1	Region					79:84	the Antibody V Region	64:84	the Antibody V Region	64:84	Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation.
30850477	7	23	theme	DE	965:966	arg1	loop					968:971	the DE loop	961:971	the DE loop	961:971	N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients.
30850477	11	24	gly	N-glycosylation	1468:1482	arg2	site					1484:1487	N-glycosylation site acquisition	1468:1499	N-glycosylation site acquisition	1468:1499	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	11	24	gly	N-glycosylation	1468:1482	arg2	acquisition					1489:1499	N-glycosylation site acquisition	1468:1499	N-glycosylation site acquisition	1468:1499	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	1	25	theme	V	154:154	arg1	regions					156:162	their V regions	148:162	their V regions	148:162	Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses.
30850477	3	26	theme	B	355:355	arg1	pathologies					373:383	several B cell-associated pathologies	347:383	several B cell-associated pathologies	347:383	Elevated N-linked glycosylation has furthermore been associated with several B cell-associated pathologies.
30850477	6	27	dep	distribution	643:654	arg1	the					639:641	the	639:641	the	639:641	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	0	28	theme	B	93:93	arg1	Maturation					100:109	B Cell Maturation	93:109	B Cell Maturation	93:109	Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation.
30850477	9	29	theme	higher	1242:1247	arg1	propensity					1249:1258	a 2-fold higher propensity	1233:1258	a 2-fold higher propensity to acquire Fab glycans	1233:1281	Interestingly, both IgE and IgG4 subsets have a 2-fold higher propensity to acquire Fab glycans compared with IgG1 or IgA.
30850477	1	30	from	glycans	137:143	arg1	regions					156:162	their V regions	148:162	their V regions	148:162	Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses.
30850477	4	31	theme	development	473:483	arg1	stages					456:461	different stages	446:461	different stages of B cell development	446:483	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	5	32	theme	sites	569:573	arg1	patterns					541:548	patterns	541:548	patterns of N-glycosylation sites	541:573	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	10	33	theme	nongermline	1353:1363	arg1	sites					1381:1385	35 out of 38 (92%) nongermline N-glycosylation sites	1334:1385	35 out of 38 (92%) nongermline N-glycosylation sites	1334:1385	When expressed as rmAb, 35 out of 38 (92%) nongermline N-glycosylation sites became occupied.
30850477	6	34	theme	N-glycosylation	675:689	arg1	sites					691:695	N-glycosylation sites	675:695	N-glycosylation sites	675:695	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	0	35	theme	Biased	0:5	arg1	Distribution					28:39	Biased N-Glycosylation Site Distribution	0:39	Biased N-Glycosylation Site Distribution	0:39	Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation.
30850477	9	36	theme	Fab	1271:1273	arg1	glycans					1275:1281	Fab glycans	1271:1281	Fab glycans	1271:1281	Interestingly, both IgE and IgG4 subsets have a 2-fold higher propensity to acquire Fab glycans compared with IgG1 or IgA.
30850477	7	37	theme	N-glycosylation	909:923	arg1	sites					925:929	N-glycosylation sites	909:929	N-glycosylation sites	909:929	N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients.
30850477	11	38	theme	selection	1446:1454	arg1	pressure					1456:1463	a differential selection pressure	1431:1463	a differential selection pressure of N-glycosylation site acquisition	1431:1499	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	0	39	theme	Site	23:26	arg1	Distribution					28:39	Biased N-Glycosylation Site Distribution	0:39	Biased N-Glycosylation Site Distribution	0:39	Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation.
30850477	6	40	theme	lupus	839:843	arg1	erythematosus					845:857	six systemic lupus erythematosus	826:857	six systemic lupus erythematosus patients	826:866	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	10	41	dep	38	1344:1345	arg1	%					1350:1350	92%	1348:1350	92%	1348:1350	When expressed as rmAb, 35 out of 38 (92%) nongermline N-glycosylation sites became occupied.
30850477	6	42	theme	bone	741:744	arg1	marrow					746:751	bone marrow	741:751	bone marrow	741:751	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	10	43	gly	N-glycosylation	1365:1379	arg2	sites					1381:1385	35 out of 38 (92%) nongermline N-glycosylation sites	1334:1385	35 out of 38 (92%) nongermline N-glycosylation sites	1334:1385	When expressed as rmAb, 35 out of 38 (92%) nongermline N-glycosylation sites became occupied.
30850477	10	43	gly	N-glycosylation	1365:1379	arg2	38					1344:1345	38	1344:1345	38	1344:1345	When expressed as rmAb, 35 out of 38 (92%) nongermline N-glycosylation sites became occupied.
30850477	11	44	theme	differential	1433:1444	arg1	pressure					1456:1463	a differential selection pressure	1431:1463	a differential selection pressure of N-glycosylation site acquisition	1431:1499	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	6	45	theme	blood	731:735	arg1	regions					709:715	Ab V regions	704:715	Ab V regions	704:715	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	3	46	link	N-linked	287:294	arg1	glycosylation					296:308	Elevated N-linked glycosylation	278:308	Elevated N-linked glycosylation	278:308	Elevated N-linked glycosylation has furthermore been associated with several B cell-associated pathologies.
30850477	6	47	gly	N-glycosylation	675:689	arg2	sites					691:695	N-glycosylation sites	675:695	N-glycosylation sites	675:695	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	8	48	theme	overall	1085:1091	arg1	bias					1103:1106	an overall selection bias	1082:1106	an overall selection bias against acquiring an N-glycosylation site	1082:1148	No evidence was found for an overall selection bias against acquiring an N-glycosylation site, except for the CDR3 of the H chain.
30850477	7	49	gly	N-glycosylation	909:923	arg2	sites					925:929	N-glycosylation sites	909:929	N-glycosylation sites	909:929	N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients.
30850477	6	50	theme	V	707:707	arg1	regions					709:715	Ab V regions	704:715	Ab V regions	704:715	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	11	51	dep	dependent	1618:1626	arg1	isotype					1597:1603	isotype	1597:1603	isotype	1597:1603	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	6	52	theme	next-generation	881:895	arg1	sequencing					897:906	next-generation sequencing	881:906	next-generation sequencing	881:906	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	12	53	theme	IgG4/IgE	1702:1709	arg1	responses					1711:1719	TH2-like IgG4/IgE responses	1693:1719	TH2-like IgG4/IgE responses	1693:1719	Elevated Fab glycosylation represents an additional hallmark of TH2-like IgG4/IgE responses.
30850477	11	54	theme	B	1531:1531	arg1	cells					1533:1537	B cells	1531:1537	B cells	1531:1537	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	4	55	theme	V	420:420	arg1	glycosylation					429:441	V region glycosylation	420:441	V region glycosylation	420:441	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	5	56	theme	memory	604:609	arg1	regions					583:589	Ab V regions	578:589	Ab V regions of naive and memory B cell subsets	578:624	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	6	57	theme	healthy	767:773	arg1	individuals					775:785	12 healthy individuals	764:785	12 healthy individuals	764:785	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	8	58	theme	N-glycosylation	1129:1143	arg1	site					1145:1148	an N-glycosylation site	1126:1148	an N-glycosylation site	1126:1148	No evidence was found for an overall selection bias against acquiring an N-glycosylation site, except for the CDR3 of the H chain.
30850477	6	59	theme	patients	859:866	arg1	blood					731:735	peripheral blood	720:735	peripheral blood	720:735	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	6	59	theme	patients	859:866	arg1	marrow					746:751	bone marrow	741:751	bone marrow	741:751	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	8	60	theme	chain	1180:1184	arg1	CDR3					1166:1169	the CDR3	1162:1169	the CDR3 of the H chain	1162:1184	No evidence was found for an overall selection bias against acquiring an N-glycosylation site, except for the CDR3 of the H chain.
30850477	11	61	theme	V	1581:1581	arg1	region					1583:1588	the V region	1577:1588	the V region	1577:1588	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	5	62	theme	cell	613:616	arg1	subsets					618:624	B cell subsets	611:624	B cell subsets	611:624	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	1	63	theme	Ag-specific	171:181	arg1	responses					190:198	Ag-specific B cell responses	171:198	Ag-specific B cell responses	171:198	Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses.
30850477	12	64	theme	additional	1670:1679	arg1	hallmark					1681:1688	an additional hallmark	1667:1688	an additional hallmark of TH2-like IgG4/IgE responses	1667:1719	Elevated Fab glycosylation represents an additional hallmark of TH2-like IgG4/IgE responses.
30850477	6	65	theme	B	753:753	arg1	cells					755:759	B cells	753:759	B cells	753:759	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	1	66	theme	cell	185:188	arg1	responses					190:198	Ag-specific B cell responses	171:198	Ag-specific B cell responses	171:198	Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses.
30850477	2	67	theme	N-linked	221:228	arg1	glycans					230:236	these N-linked glycans	215:236	these N-linked glycans	215:236	Among others, these N-linked glycans can affect Ag binding and Ab stability.
30850477	5	68	dep	naive	594:598	arg1	subsets					618:624	B cell subsets	611:624	B cell subsets	611:624	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	4	69	theme	cell	468:471	arg1	development					473:483	B cell development	466:483	B cell development	466:483	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	7	70	theme	similar	1003:1009	arg1	frequencies					1011:1021	similar frequencies	1003:1021	similar frequencies for healthy donors and patients	1003:1053	N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients.
30850477	4	71	theme	glycosylation	429:441	arg1	patterns					408:415	patterns	408:415	patterns of V region glycosylation	408:441	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	11	72	theme	site	1484:1487	arg1	acquisition					1489:1499	N-glycosylation site acquisition	1468:1499	N-glycosylation site acquisition	1468:1499	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	9	73	theme	IgE	1207:1209	arg1	subsets					1220:1226	both IgE and IgG4 subsets	1202:1226	both IgE and IgG4 subsets	1202:1226	Interestingly, both IgE and IgG4 subsets have a 2-fold higher propensity to acquire Fab glycans compared with IgG1 or IgA.
30850477	2	74	theme	Ag	249:250	arg1	binding					252:258	Ag binding	249:258	Ag binding	249:258	Among others, these N-linked glycans can affect Ag binding and Ab stability.
30850477	5	75	theme	N-glycosylation	553:567	arg1	sites					569:573	N-glycosylation sites	553:573	N-glycosylation sites	553:573	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	3	76	theme	Elevated	278:285	arg1	glycosylation					296:308	Elevated N-linked glycosylation	278:308	Elevated N-linked glycosylation	278:308	Elevated N-linked glycosylation has furthermore been associated with several B cell-associated pathologies.
30850477	4	77	theme	different	446:454	arg1	stages					456:461	different stages	446:461	different stages of B cell development	446:483	Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce.
30850477	0	78	theme	V	77:77	arg1	Region					79:84	the Antibody V Region	64:84	the Antibody V Region	64:84	Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation.
30850477	9	79	theme	IgG4	1215:1218	arg1	subsets					1220:1226	both IgE and IgG4 subsets	1202:1226	both IgE and IgG4 subsets	1202:1226	Interestingly, both IgE and IgG4 subsets have a 2-fold higher propensity to acquire Fab glycans compared with IgG1 or IgA.
30850477	5	80	theme	study	519:523	arg1	aim					500:502	The aim	496:502	The aim of the current study	496:523	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	12	81	theme	Elevated	1629:1636	arg1	glycosylation					1642:1654	Elevated Fab glycosylation	1629:1654	Elevated Fab glycosylation	1629:1654	Elevated Fab glycosylation represents an additional hallmark of TH2-like IgG4/IgE responses.
30850477	6	82	theme	gravis	805:810	arg1	patients					812:819	eight myasthenia gravis patients	788:819	eight myasthenia gravis patients	788:819	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	0	83	theme	Cell	95:98	arg1	Maturation					100:109	B Cell Maturation	93:109	B Cell Maturation	93:109	Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation.
30850477	5	84	theme	naive	594:598	arg1	regions					583:589	Ab V regions	578:589	Ab V regions of naive and memory B cell subsets	578:624	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	3	85	theme	cell-associated	357:371	arg1	pathologies					373:383	several B cell-associated pathologies	347:383	several B cell-associated pathologies	347:383	Elevated N-linked glycosylation has furthermore been associated with several B cell-associated pathologies.
30850477	6	86	theme	Ab	704:705	arg1	regions					709:715	Ab V regions	704:715	Ab V regions	704:715	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	3	87	theme	several	347:353	arg1	pathologies					373:383	several B cell-associated pathologies	347:383	several B cell-associated pathologies	347:383	Elevated N-linked glycosylation has furthermore been associated with several B cell-associated pathologies.
30850477	10	88	theme	N-glycosylation	1365:1379	arg1	sites					1381:1385	35 out of 38 (92%) nongermline N-glycosylation sites	1334:1385	35 out of 38 (92%) nongermline N-glycosylation sites	1334:1385	When expressed as rmAb, 35 out of 38 (92%) nongermline N-glycosylation sites became occupied.
30850477	6	89	theme	sites	691:695	arg1	acquisition					660:670	acquisition	660:670	acquisition	660:670	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	6	89	theme	sites	691:695	arg1	distribution					643:654	distribution	643:654	distribution	643:654	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	0	90	theme	N-Glycosylation	7:21	arg1	Distribution					28:39	Biased N-Glycosylation Site Distribution	0:39	Biased N-Glycosylation Site Distribution	0:39	Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation.
30850477	5	91	theme	V	581:581	arg1	regions					583:589	Ab V regions	578:589	Ab V regions of naive and memory B cell subsets	578:624	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	5	92	gly	N-glycosylation	553:567	arg2	sites					569:573	N-glycosylation sites	553:573	N-glycosylation sites	553:573	The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets.
30850477	6	93	theme	systemic	830:837	arg1	erythematosus					845:857	six systemic lupus erythematosus	826:857	six systemic lupus erythematosus patients	826:866	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	6	94	theme	marrow	746:751	arg1	regions					709:715	Ab V regions	704:715	Ab V regions	704:715	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	7	95	theme	healthy	1027:1033	arg1	donors					1035:1040	healthy donors	1027:1040	healthy donors	1027:1040	N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients.
30850477	1	96	link	N-linked	128:135	arg1	glycans					137:143	N-linked glycans	128:143	N-linked glycans in their V regions	128:162	Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses.
30850477	11	97	theme	affinity	1508:1515	arg1	maturation					1517:1526	affinity maturation	1508:1526	affinity maturation	1508:1526	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	6	98	theme	patients	812:819	arg1	blood					731:735	peripheral blood	720:735	peripheral blood	720:735	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	6	98	theme	patients	812:819	arg1	marrow					746:751	bone marrow	741:751	bone marrow	741:751	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	11	99	theme	cells	1533:1537	arg1	maturation					1517:1526	affinity maturation	1508:1526	affinity maturation	1508:1526	These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent.
30850477	6	100	theme	peripheral	720:729	arg1	blood					731:735	peripheral blood	720:735	peripheral blood	720:735	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	9	101	contain	have	1228:1231	arg1	subsets					1220:1226	both IgE and IgG4 subsets	1202:1226	both IgE and IgG4 subsets	1202:1226	Interestingly, both IgE and IgG4 subsets have a 2-fold higher propensity to acquire Fab glycans compared with IgG1 or IgA.
30850477	9	101	contain	have	1228:1231	arg2	propensity					1249:1258	a 2-fold higher propensity	1233:1258	a 2-fold higher propensity to acquire Fab glycans	1233:1281	Interestingly, both IgE and IgG4 subsets have a 2-fold higher propensity to acquire Fab glycans compared with IgG1 or IgA.
30850477	8	102	theme	selection	1093:1101	arg1	bias					1103:1106	an overall selection bias	1082:1106	an overall selection bias against acquiring an N-glycosylation site	1082:1148	No evidence was found for an overall selection bias against acquiring an N-glycosylation site, except for the CDR3 of the H chain.
30850477	6	103	theme	myasthenia	794:803	arg1	gravis					805:810	eight myasthenia gravis	788:810	eight myasthenia gravis patients	788:819	We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing.
30850477	12	104	theme	responses	1711:1719	arg1	hallmark					1681:1688	an additional hallmark	1667:1688	an additional hallmark of TH2-like IgG4/IgE responses	1667:1719	Elevated Fab glycosylation represents an additional hallmark of TH2-like IgG4/IgE responses.
30850477	8	105	gly	N-glycosylation	1129:1143	arg2	site					1145:1148	an N-glycosylation site	1126:1148	an N-glycosylation site	1126:1148	No evidence was found for an overall selection bias against acquiring an N-glycosylation site, except for the CDR3 of the H chain.
30538676	0	0	theme	Epithelial	92:101	arg1	Cells					103:107	Human Bronchial Epithelial Cells	76:107	Human Bronchial Epithelial Cells	76:107	FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
30538676	3	1	theme	/nuclear	676:683	arg1	NFAT					714:717	NFAT	714:717	NFAT	714:717	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	1	theme	/nuclear	676:683	arg1	factor					685:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor	643:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	643:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	9	2	theme	metabolic	1705:1713	arg1	syndromes					1715:1723	metabolic syndromes	1705:1723	COPD and CF as well as metabolic syndromes	1682:1723	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	5	3	theme	NFAT	1046:1049	arg1	secretion					1055:1063	secretion	1055:1063	secretion of interleukin-6 (IL-6)	1055:1087	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	5	3	theme	NFAT	1046:1049	arg1	activation					1032:1041	the downstream activation	1017:1041	the downstream activation of NFAT	1017:1049	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	0	4	theme	Bronchial	82:90	arg1	Cells					103:107	Human Bronchial Epithelial Cells	76:107	Human Bronchial Epithelial Cells	76:107	FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
30538676	7	5	theme	O-GlcNAc	1350:1357	arg1	levels					1359:1364	the HBP and O-GlcNAc levels	1338:1364	levels	1359:1364	Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs.
30538676	2	6	theme	factor	341:346	arg1	activation					376:385	nuclear factor of activated T-cells (NFAT) activation	333:385	nuclear factor of activated T-cells (NFAT) activation	333:385	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	4	7	from	modification	904:915	arg1	HBECs					932:936	HBECs	932:936	HBECs	932:936	Here, we demonstrate that FGF23 increased the O-GlcNAc modification of proteins in HBECs.
30538676	4	8	theme	O-GlcNAc	895:902	arg1	modification					904:915	the O-GlcNAc modification	891:915	the O-GlcNAc modification of proteins in HBECs	891:936	Here, we demonstrate that FGF23 increased the O-GlcNAc modification of proteins in HBECs.
30538676	3	9	theme	PLCγ	671:674	arg1	NFAT					714:717	NFAT	714:717	NFAT	714:717	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	9	theme	PLCγ	671:674	arg1	factor					685:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor	643:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	643:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	10	theme	Factor	554:559	arg1	mediator					611:618	an important endocrine pro-inflammatory mediator	571:618	an important endocrine pro-inflammatory mediator	571:618	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	10	theme	Factor	554:559	arg1	FGF					562:564	Fibroblast Growth Factor (FGF) 23	536:568	Fibroblast Growth Factor (FGF) 23	536:568	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	11	theme	activated	695:703	arg1	T-cells					705:711	activated T-cells	695:711	activated T-cells	695:711	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	12	theme	Fibroblast	536:545	arg1	mediator					611:618	an important endocrine pro-inflammatory mediator	571:618	an important endocrine pro-inflammatory mediator	571:618	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	12	theme	Fibroblast	536:545	arg1	FGF					562:564	Fibroblast Growth Factor (FGF) 23	536:568	Fibroblast Growth Factor (FGF) 23	536:568	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	1	13	mod	modification	226:237	arg3	β-N-acetylglucosamine					193:213	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification	180:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	180:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	1	13	mod	modification	226:237	arg1	proteins					242:249	proteins	242:249	proteins	242:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	1	13	mod	modification	226:237	arg3	O-GlcNAc					216:223	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification	180:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	180:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	2	14	theme	nuclear	333:339	arg1	NFAT					370:373	NFAT	370:373	NFAT	370:373	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	14	theme	nuclear	333:339	arg1	factor					341:346	nuclear factor	333:346	nuclear factor of activated T-cells (NFAT) activation	333:385	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	1	15	link	O-linked	184:191	arg1	modification					226:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification	180:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	180:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	3	16	theme	cystic	778:783	arg1	CF					795:796	CF	795:796	CF	795:796	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	16	theme	cystic	778:783	arg1	fibrosis					785:792	cystic fibrosis	778:792	cystic fibrosis (CF)	778:797	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	2	17	theme	stress	277:282	arg1	sensor					284:289	a stress sensor	275:289	a stress sensor	275:289	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	17	theme	stress	277:282	arg1	HBP					256:258	The HBP	252:258	The HBP	252:258	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	5	18	from	increase	956:963	arg1	levels					977:982	O-GlcNAc levels	968:982	O-GlcNAc levels	968:982	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	7	19	from	activation	1324:1333	arg1	HBECs					1369:1373	HBECs	1369:1373	HBECs	1369:1373	Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs.
30538676	3	20	theme	factor	685:690	arg1	signaling					720:728	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling	643:728	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	643:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	8	21	theme	O-GlcNAc	1451:1458	arg1	levels					1460:1465	O-GlcNAc levels	1451:1465	O-GlcNAc levels	1451:1465	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	2	22	theme	cellular	421:428	arg1	proliferation					467:479	proliferation	467:479	proliferation	467:479	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	22	theme	cellular	421:428	arg1	processes					430:438	multiple cellular processes	412:438	multiple cellular processes including cell metabolism, proliferation, and inflammation	412:497	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	22	theme	cellular	421:428	arg1	metabolism					455:464	cell metabolism	450:464	cell metabolism	450:464	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	22	theme	cellular	421:428	arg1	inflammation					486:497	inflammation	486:497	inflammation	486:497	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	8	23	theme	levels	1460:1465	arg1	FGF23					1421:1425	FGF23	1421:1425	FGF23	1421:1425	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	8	23	theme	levels	1460:1465	arg1	augmentation					1435:1446	the augmentation	1431:1446	the augmentation of O-GlcNAc levels	1431:1465	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	7	24	theme	HBP	1342:1344	arg1	levels					1359:1364	the HBP and O-GlcNAc levels	1338:1364	levels	1359:1364	Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs.
30538676	3	25	theme	T-cells	705:711	arg1	NFAT					714:717	NFAT	714:717	NFAT	714:717	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	25	theme	T-cells	705:711	arg1	factor					685:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor	643:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	643:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	1	26	theme	O-linked	184:191	arg1	modification					226:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification	180:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	180:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	0	27	theme	FGF23	0:4	arg1	Induction					6:14	FGF23 Induction	0:14	FGF23 Induction of O-Linked N-Acetylglucosamine	0:46	FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
30538676	8	28	from	upregulation	1529:1540	arg1	HBECs					1545:1549	HBECs	1545:1549	HBECs	1545:1549	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	3	29	from	signaling	720:728	arg1	diseases					761:768	chronic inflammatory airway diseases	733:768	chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	733:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	29	from	signaling	720:728	arg1	disease					833:839	chronic obstructive pulmonary disease	803:839	chronic obstructive pulmonary disease (COPD)	803:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	29	from	signaling	720:728	arg1	fibrosis					785:792	cystic fibrosis	778:792	cystic fibrosis (CF)	778:797	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	5	30	theme	FGF23	987:991	arg1	stimulation					993:1003	FGF23 stimulation	987:1003	FGF23 stimulation	987:1003	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	1	31	theme	β-N-acetylglucosamine	193:213	arg1	modification					226:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification	180:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	180:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	0	32	theme	O-Linked	19:26	arg1	N-Acetylglucosamine					28:46	O-Linked N-Acetylglucosamine	19:46	O-Linked N-Acetylglucosamine	19:46	FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
30538676	6	33	theme	transferase	1148:1158	arg1	/O-GlcNAc					1165:1173	O-GlcNAc transferase (OGT)/O-GlcNAc	1139:1173	O-GlcNAc transferase (OGT)/O-GlcNAc	1139:1173	Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects.
30538676	9	34	theme	inflammatory	1645:1656	arg1	diseases					1665:1672	chronic inflammatory airway diseases	1637:1672	chronic inflammatory airway diseases	1637:1672	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	34	theme	inflammatory	1645:1656	arg1	COPD					1682:1685	COPD	1682:1685	COPD	1682:1685	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	34	theme	inflammatory	1645:1656	arg1	diabetes					1736:1743	diabetes	1736:1743	diabetes	1736:1743	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	34	theme	inflammatory	1645:1656	arg1	syndromes					1715:1723	metabolic syndromes	1705:1723	COPD and CF as well as metabolic syndromes	1682:1723	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	34	theme	inflammatory	1645:1656	arg1	CF					1691:1692	CF	1691:1692	CF	1691:1692	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	35	theme	chronic	1637:1643	arg1	diseases					1665:1672	chronic inflammatory airway diseases	1637:1672	chronic inflammatory airway diseases	1637:1672	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	35	theme	chronic	1637:1643	arg1	COPD					1682:1685	COPD	1682:1685	COPD	1682:1685	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	35	theme	chronic	1637:1643	arg1	diabetes					1736:1743	diabetes	1736:1743	diabetes	1736:1743	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	35	theme	chronic	1637:1643	arg1	syndromes					1715:1723	metabolic syndromes	1705:1723	COPD and CF as well as metabolic syndromes	1682:1723	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	35	theme	chronic	1637:1643	arg1	CF					1691:1692	CF	1691:1692	CF	1691:1692	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	3	36	theme	Growth	547:552	arg1	mediator					611:618	an important endocrine pro-inflammatory mediator	571:618	an important endocrine pro-inflammatory mediator	571:618	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	36	theme	Growth	547:552	arg1	FGF					562:564	Fibroblast Growth Factor (FGF) 23	536:568	Fibroblast Growth Factor (FGF) 23	536:568	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	7	37	theme	IL-6	1251:1254	arg1	upregulation					1256:1267	FGF23 induced IL-6 upregulation	1237:1267	FGF23 induced IL-6 upregulation	1237:1267	Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs.
30538676	8	38	theme	novel	1402:1406	arg1	link					1408:1411	a novel link	1400:1411	a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs	1400:1549	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	8	39	theme	NFAT	1504:1507	arg1	activation					1509:1518	NFAT activation	1504:1518	NFAT activation	1504:1518	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	3	40	theme	published	518:526	arg1	report					528:533	our previously published report	503:533	our previously published report	503:533	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	1	41	theme	hexosamine	114:123	arg1	HBP					147:149	HBP	147:149	HBP	147:149	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	1	41	theme	hexosamine	114:123	arg1	pathway					138:144	The hexosamine biosynthetic pathway	110:144	The hexosamine biosynthetic pathway (HBP)	110:150	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	1	42	theme	O-GlcNAc	216:223	arg1	modification					226:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification	180:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	180:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	8	43	theme	IL-6	1524:1527	arg1	upregulation					1529:1540	IL-6 upregulation	1524:1540	IL-6 upregulation	1524:1540	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	9	44	theme	diseases	1665:1672	arg1	pathogenesis					1621:1632	the pathogenesis	1617:1632	the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes	1617:1743	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	5	45	theme	downstream	1021:1030	arg1	activation					1032:1041	the downstream activation	1017:1041	the downstream activation of NFAT	1017:1049	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	6	46	theme	O-GlcNAc	1139:1146	arg1	OGT					1161:1163	OGT	1161:1163	OGT	1161:1163	Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects.
30538676	6	46	theme	O-GlcNAc	1139:1146	arg1	transferase					1148:1158	O-GlcNAc transferase	1139:1158	O-GlcNAc transferase (OGT)/O-GlcNAc	1139:1173	Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects.
30538676	7	47	theme	FGF23	1237:1241	arg1	upregulation					1256:1267	FGF23 induced IL-6 upregulation	1237:1267	FGF23 induced IL-6 upregulation	1237:1267	Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs.
30538676	0	48	theme	N-Acetylglucosamine	28:46	arg1	Induction					6:14	FGF23 Induction	0:14	FGF23 Induction of O-Linked N-Acetylglucosamine	0:46	FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
30538676	3	49	theme	inflammatory	741:752	arg1	diseases					761:768	chronic inflammatory airway diseases	733:768	chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	733:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	49	theme	inflammatory	741:752	arg1	disease					833:839	chronic obstructive pulmonary disease	803:839	chronic obstructive pulmonary disease (COPD)	803:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	49	theme	inflammatory	741:752	arg1	fibrosis					785:792	cystic fibrosis	778:792	cystic fibrosis (CF)	778:797	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	2	50	theme	multiple	412:419	arg1	proliferation					467:479	proliferation	467:479	proliferation	467:479	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	50	theme	multiple	412:419	arg1	processes					430:438	multiple cellular processes	412:438	multiple cellular processes including cell metabolism, proliferation, and inflammation	412:497	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	50	theme	multiple	412:419	arg1	metabolism					455:464	cell metabolism	450:464	cell metabolism	450:464	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	50	theme	multiple	412:419	arg1	inflammation					486:497	inflammation	486:497	inflammation	486:497	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	7	51	theme	induced	1243:1249	arg1	upregulation					1256:1267	FGF23 induced IL-6 upregulation	1237:1267	FGF23 induced IL-6 upregulation	1237:1267	Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs.
30538676	2	52	theme	cell	450:453	arg1	metabolism					455:464	cell metabolism	450:464	cell metabolism	450:464	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	3	53	theme	airway	754:759	arg1	diseases					761:768	chronic inflammatory airway diseases	733:768	chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	733:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	53	theme	airway	754:759	arg1	disease					833:839	chronic obstructive pulmonary disease	803:839	chronic obstructive pulmonary disease (COPD)	803:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	53	theme	airway	754:759	arg1	fibrosis					785:792	cystic fibrosis	778:792	cystic fibrosis (CF)	778:797	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	8	54	theme	airway	1476:1481	arg1	inflammation					1483:1494	airway inflammation	1476:1494	airway inflammation	1476:1494	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	6	55	theme	/O-GlcNAc	1165:1173	arg1	inhibition					1102:1111	inhibition	1102:1111	inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc	1102:1173	Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects.
30538676	1	56	theme	biosynthetic	125:136	arg1	HBP					147:149	HBP	147:149	HBP	147:149	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	1	56	theme	biosynthetic	125:136	arg1	pathway					138:144	The hexosamine biosynthetic pathway	110:144	The hexosamine biosynthetic pathway (HBP)	110:150	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	0	57	theme	IL-6	58:61	arg1	Secretion					63:71	IL-6 Secretion	58:71	IL-6 Secretion	58:71	FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
30538676	6	58	theme	signaling	1122:1130	arg1	inhibition					1102:1111	inhibition	1102:1111	inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc	1102:1173	Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects.
30538676	3	59	theme	FGFR4/phospholipase	647:665	arg1	NFAT					714:717	NFAT	714:717	NFAT	714:717	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	59	theme	FGFR4/phospholipase	647:665	arg1	factor					685:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor	643:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	643:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	60	theme	obstructive	811:821	arg1	COPD					842:845	COPD	842:845	COPD	842:845	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	60	theme	obstructive	811:821	arg1	disease					833:839	chronic obstructive pulmonary disease	803:839	chronic obstructive pulmonary disease (COPD)	803:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	61	theme	chronic	733:739	arg1	diseases					761:768	chronic inflammatory airway diseases	733:768	chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	733:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	61	theme	chronic	733:739	arg1	disease					833:839	chronic obstructive pulmonary disease	803:839	chronic obstructive pulmonary disease (COPD)	803:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	61	theme	chronic	733:739	arg1	fibrosis					785:792	cystic fibrosis	778:792	cystic fibrosis (CF)	778:797	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	62	theme	Cγ	667:668	arg1	NFAT					714:717	NFAT	714:717	NFAT	714:717	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	62	theme	Cγ	667:668	arg1	factor					685:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor	643:690	the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD)	643:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	63	theme	pro-inflammatory	594:609	arg1	FGF					562:564	Fibroblast Growth Factor (FGF) 23	536:568	Fibroblast Growth Factor (FGF) 23	536:568	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	63	theme	pro-inflammatory	594:609	arg1	mediator					611:618	an important endocrine pro-inflammatory mediator	571:618	an important endocrine pro-inflammatory mediator	571:618	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	5	64	theme	O-GlcNAc	968:975	arg1	levels					977:982	O-GlcNAc levels	968:982	O-GlcNAc levels	968:982	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	3	65	theme	pulmonary	823:831	arg1	COPD					842:845	COPD	842:845	COPD	842:845	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	65	theme	pulmonary	823:831	arg1	disease					833:839	chronic obstructive pulmonary disease	803:839	chronic obstructive pulmonary disease (COPD)	803:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	7	66	theme	levels	1359:1364	arg1	activation					1324:1333	the activation	1320:1333	the activation of the HBP and O-GlcNAc levels in HBECs	1320:1373	Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs.
30538676	8	67	from	activation	1509:1518	arg1	HBECs					1545:1549	HBECs	1545:1549	HBECs	1545:1549	These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs.
30538676	6	68	theme	FGF23	1116:1120	arg1	signaling					1122:1130	FGF23 signaling	1116:1130	FGF23 signaling	1116:1130	Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects.
30538676	9	69	theme	signaling	1580:1588	arg1	pathways					1590:1597	these signaling pathways	1574:1597	these signaling pathways	1574:1597	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	1	70	theme	proteins	242:249	arg1	modification					226:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification	180:237	the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	180:249	The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins.
30538676	0	71	theme	Human	76:80	arg1	Cells					103:107	Human Bronchial Epithelial Cells	76:107	Human Bronchial Epithelial Cells	76:107	FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
30538676	3	72	theme	important	574:582	arg1	FGF					562:564	Fibroblast Growth Factor (FGF) 23	536:568	Fibroblast Growth Factor (FGF) 23	536:568	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	72	theme	important	574:582	arg1	mediator					611:618	an important endocrine pro-inflammatory mediator	571:618	an important endocrine pro-inflammatory mediator	571:618	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	2	73	theme	T-cells	361:367	arg1	NFAT					370:373	NFAT	370:373	NFAT	370:373	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	2	73	theme	T-cells	361:367	arg1	factor					341:346	nuclear factor	333:346	nuclear factor of activated T-cells (NFAT) activation	333:385	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	3	74	theme	chronic	803:809	arg1	COPD					842:845	COPD	842:845	COPD	842:845	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	74	theme	chronic	803:809	arg1	disease					833:839	chronic obstructive pulmonary disease	803:839	chronic obstructive pulmonary disease (COPD)	803:846	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	4	75	theme	proteins	920:927	arg1	modification					904:915	the O-GlcNAc modification	891:915	the O-GlcNAc modification of proteins in HBECs	891:936	Here, we demonstrate that FGF23 increased the O-GlcNAc modification of proteins in HBECs.
30538676	5	76	theme	interleukin-6	1068:1080	arg1	secretion					1055:1063	secretion	1055:1063	secretion of interleukin-6 (IL-6)	1055:1087	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	5	76	theme	interleukin-6	1068:1080	arg1	activation					1032:1041	the downstream activation	1017:1041	the downstream activation of NFAT	1017:1049	Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6).
30538676	3	77	theme	endocrine	584:592	arg1	FGF					562:564	Fibroblast Growth Factor (FGF) 23	536:568	Fibroblast Growth Factor (FGF) 23	536:568	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	3	77	theme	endocrine	584:592	arg1	mediator					611:618	an important endocrine pro-inflammatory mediator	571:618	an important endocrine pro-inflammatory mediator	571:618	In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
30538676	2	78	theme	activated	351:359	arg1	T-cells					361:367	activated T-cells	351:367	activated T-cells	351:367	The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation.
30538676	9	79	theme	airway	1658:1663	arg1	diseases					1665:1672	chronic inflammatory airway diseases	1637:1672	chronic inflammatory airway diseases	1637:1672	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	79	theme	airway	1658:1663	arg1	COPD					1682:1685	COPD	1682:1685	COPD	1682:1685	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	79	theme	airway	1658:1663	arg1	diabetes					1736:1743	diabetes	1736:1743	diabetes	1736:1743	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	79	theme	airway	1658:1663	arg1	syndromes					1715:1723	metabolic syndromes	1705:1723	COPD and CF as well as metabolic syndromes	1682:1723	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
30538676	9	79	theme	airway	1658:1663	arg1	CF					1691:1692	CF	1691:1692	CF	1691:1692	The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
31822723	2	0	theme	interfacial	358:368	arg1	formation					412:420	formation	412:420	formation of organo-mineral associations	412:451	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	2	0	theme	interfacial	358:368	arg1	transformations					392:406	OM transformations	389:406	OM transformations	389:406	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	2	0	theme	interfacial	358:368	arg1	reactions					370:378	interfacial reactions	358:378	interfacial reactions	358:378	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	5	1	theme	SWI	780:782	arg1	processes					784:792	SWI processes	780:792	SWI processes	780:792	Dissolved organic matter from the original soil was added on the SoilChips to mimic SWI processes.
31822723	6	2	theme	photoelectron	910:922	arg1	spectroscopy					924:935	X-ray photoelectron spectroscopy	904:935	X-ray photoelectron spectroscopy	904:935	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	9	3	theme	specific	1293:1300	arg1	processing					1315:1324	the specific OM molecular processing	1289:1324	the specific OM molecular processing	1289:1324	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	1	4	theme	soil	183:186	arg1	pores					188:192	soil pores	183:192	soil pores	183:192	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	4	5	theme	800-μm-diameter	577:591	arg1	SoilChips					593:601	Homogeneous 800-μm-diameter SoilChips	565:601	Homogeneous 800-μm-diameter SoilChips	565:601	Homogeneous 800-μm-diameter SoilChips were constructed by depositing a dispersed Oxisol A horizon suspension on a patterned glass.
31822723	0	6	theme	polysaccharides	121:135	arg1	synthesis					137:145	microbial polysaccharides synthesis	111:145	microbial polysaccharides synthesis	111:145	Nitrogen fertilization modifies organic transformations and coatings on soil biogeochemical interfaces through microbial polysaccharides synthesis.
31822723	6	7	theme	X-ray	904:908	arg1	spectroscopy					924:935	X-ray photoelectron spectroscopy	904:935	X-ray photoelectron spectroscopy	904:935	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	6	8	theme	fertilization	819:831	arg1	effects					799:805	The effects	795:805	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs	795:883	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	0	9	theme	microbial	111:119	arg1	synthesis					137:145	microbial polysaccharides synthesis	111:145	microbial polysaccharides synthesis	111:145	Nitrogen fertilization modifies organic transformations and coatings on soil biogeochemical interfaces through microbial polysaccharides synthesis.
31822723	6	10	theme	ammonium	810:817	arg1	soil					847:850	90 mg N kg-1 soil	834:850	90 mg N kg-1 soil	834:850	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	6	10	theme	ammonium	810:817	arg1	fertilization					819:831	ammonium fertilization	810:831	ammonium fertilization (90 mg N kg-1 soil)	810:851	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	2	11	theme	opaque	285:290	arg1	nature					292:297	the heterogeneous and opaque nature	263:297	the heterogeneous and opaque nature of soil microenvironment	263:322	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	4	12	theme	Oxisol	646:651	arg1	suspension					663:672	a dispersed Oxisol A horizon suspension	634:672	a dispersed Oxisol A horizon suspension	634:672	Homogeneous 800-μm-diameter SoilChips were constructed by depositing a dispersed Oxisol A horizon suspension on a patterned glass.
31822723	8	13	theme	microbial	1211:1219	arg1	production					1221:1230	the microbial production	1207:1230	the microbial production of glucans	1207:1241	Molecular modeling of OM composition at SWIs showed that N fertilization mainly facilitated the microbial production of glucans.
31822723	9	14	from	processing	1315:1324	arg1	SWIs					1352:1355	SWIs	1352:1355	SWIs	1352:1355	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	8	15	theme	glucans	1235:1241	arg1	production					1221:1230	the microbial production	1207:1230	the microbial production of glucans	1207:1241	Molecular modeling of OM composition at SWIs showed that N fertilization mainly facilitated the microbial production of glucans.
31822723	1	16	from	interfaces	163:172	arg1	pores					188:192	soil pores	183:192	soil pores	183:192	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	2	17	theme	heterogeneous	267:279	arg1	nature					292:297	the heterogeneous and opaque nature	263:297	the heterogeneous and opaque nature of soil microenvironment	263:322	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	9	18	theme	N	1265:1265	arg1	availability					1267:1278	N availability	1265:1278	N availability	1265:1278	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	2	19	theme	OM	389:390	arg1	transformations					392:406	OM transformations	389:406	OM transformations	389:406	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	7	20	theme	ammonium	952:959	arg1	addition					961:968	ammonium addition	952:968	ammonium addition	952:968	Over 21 days, ammonium addition increased OM coatings at SWIs and modified the OM chemical structure with more alcoholic- and carboxylic-C compared to the unfertilized control.
31822723	6	21	theme	SWIs	880:883	arg1	composition					865:875	chemical composition	856:875	chemical composition of SWIs	856:883	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	8	22	theme	Molecular	1115:1123	arg1	modeling					1125:1132	Molecular modeling	1115:1132	Molecular modeling of OM composition at SWIs	1115:1158	Molecular modeling of OM composition at SWIs showed that N fertilization mainly facilitated the microbial production of glucans.
31822723	0	23	theme	Nitrogen	0:7	arg1	fertilization					9:21	Nitrogen fertilization	0:21	Nitrogen fertilization	0:21	Nitrogen fertilization modifies organic transformations and coatings on soil biogeochemical interfaces through microbial polysaccharides synthesis.
31822723	7	24	theme	unfertilized	1093:1104	arg1	control					1106:1112	the unfertilized control	1089:1112	the unfertilized control	1089:1112	Over 21 days, ammonium addition increased OM coatings at SWIs and modified the OM chemical structure with more alcoholic- and carboxylic-C compared to the unfertilized control.
31822723	2	25	theme	microenvironment	307:322	arg1	nature					292:297	the heterogeneous and opaque nature	263:297	the heterogeneous and opaque nature of soil microenvironment	263:322	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	4	26	theme	patterned	679:687	arg1	glass					689:693	a patterned glass	677:693	a patterned glass	677:693	Homogeneous 800-μm-diameter SoilChips were constructed by depositing a dispersed Oxisol A horizon suspension on a patterned glass.
31822723	0	27	theme	organic	32:38	arg1	transformations					40:54	organic transformations	32:54	organic transformations	32:54	Nitrogen fertilization modifies organic transformations and coatings on soil biogeochemical interfaces through microbial polysaccharides synthesis.
31822723	2	28	theme	soil	302:305	arg1	microenvironment					307:322	soil microenvironment	302:322	soil microenvironment	302:322	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	2	29	theme	organo-mineral	425:438	arg1	associations					440:451	organo-mineral associations	425:451	organo-mineral associations	425:451	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	2	30	theme	associations	440:451	arg1	formation					412:420	formation	412:420	formation of organo-mineral associations	412:451	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	2	30	theme	associations	440:451	arg1	transformations					392:406	OM transformations	389:406	OM transformations	389:406	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	4	31	theme	Homogeneous	565:575	arg1	SoilChips					593:601	Homogeneous 800-μm-diameter SoilChips	565:601	Homogeneous 800-μm-diameter SoilChips	565:601	Homogeneous 800-μm-diameter SoilChips were constructed by depositing a dispersed Oxisol A horizon suspension on a patterned glass.
31822723	3	32	theme	microarray	507:516	arg1	SoilChips					530:538	SoilChips	530:538	SoilChips	530:538	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31822723	3	32	theme	microarray	507:516	arg1	technology					518:527	a new soil microarray technology	496:527	a new soil microarray technology (SoilChips)	496:539	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31822723	1	33	theme	matter	219:224	arg1	transformation					231:244	organic matter (OM) transformation	211:244	organic matter (OM) transformation	211:244	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	3	34	theme	soil	502:505	arg1	SoilChips					530:538	SoilChips	530:538	SoilChips	530:538	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31822723	3	34	theme	soil	502:505	arg1	technology					518:527	a new soil microarray technology	496:527	a new soil microarray technology (SoilChips)	496:539	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31822723	2	35	theme	continuous	336:345	arg1	tracing					347:353	direct and continuous tracing	325:353	direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations,	325:452	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	5	36	theme	original	730:737	arg1	soil					739:742	the original soil	726:742	the original soil	726:742	Dissolved organic matter from the original soil was added on the SoilChips to mimic SWI processes.
31822723	8	37	from	SWIs	1155:1158	arg1	modeling					1125:1132	Molecular modeling	1115:1132	Molecular modeling of OM composition at SWIs	1115:1158	Molecular modeling of OM composition at SWIs showed that N fertilization mainly facilitated the microbial production of glucans.
31822723	6	38	from	effects	799:805	arg1	composition					865:875	chemical composition	856:875	chemical composition of SWIs	856:883	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	8	39	theme	OM	1137:1138	arg1	composition					1140:1150	OM composition	1137:1150	OM composition	1137:1150	Molecular modeling of OM composition at SWIs showed that N fertilization mainly facilitated the microbial production of glucans.
31822723	5	40	from	soil	739:742	arg1	matter					714:719	Dissolved organic matter	696:719	Dissolved organic matter from the original soil	696:742	Dissolved organic matter from the original soil was added on the SoilChips to mimic SWI processes.
31822723	6	41	theme	chemical	856:863	arg1	composition					865:875	chemical composition	856:875	chemical composition of SWIs	856:883	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	9	42	from	immobilization	1334:1347	arg1	SWIs					1352:1355	SWIs	1352:1355	SWIs	1352:1355	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	7	43	theme	OM	1017:1018	arg1	structure					1029:1037	the OM chemical structure	1013:1037	the OM chemical structure	1013:1037	Over 21 days, ammonium addition increased OM coatings at SWIs and modified the OM chemical structure with more alcoholic- and carboxylic-C compared to the unfertilized control.
31822723	4	44	theme	horizon	655:661	arg1	suspension					663:672	a dispersed Oxisol A horizon suspension	634:672	a dispersed Oxisol A horizon suspension	634:672	Homogeneous 800-μm-diameter SoilChips were constructed by depositing a dispersed Oxisol A horizon suspension on a patterned glass.
31822723	9	45	theme	OM	1302:1303	arg1	processing					1315:1324	the specific OM molecular processing	1289:1324	the specific OM molecular processing	1289:1324	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	8	46	theme	N	1172:1172	arg1	fertilization					1174:1186	N fertilization	1172:1186	N fertilization	1172:1186	Molecular modeling of OM composition at SWIs showed that N fertilization mainly facilitated the microbial production of glucans.
31822723	8	47	theme	composition	1140:1150	arg1	modeling					1125:1132	Molecular modeling	1115:1132	Molecular modeling of OM composition at SWIs	1115:1158	Molecular modeling of OM composition at SWIs showed that N fertilization mainly facilitated the microbial production of glucans.
31822723	7	48	theme	chemical	1020:1027	arg1	structure					1029:1037	the OM chemical structure	1013:1037	the OM chemical structure	1013:1037	Over 21 days, ammonium addition increased OM coatings at SWIs and modified the OM chemical structure with more alcoholic- and carboxylic-C compared to the unfertilized control.
31822723	3	49	used	used	559:562	arg2	SoilChips					530:538	SoilChips	530:538	SoilChips	530:538	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31822723	3	49	used	used	559:562	arg2	technology					518:527	a new soil microarray technology	496:527	a new soil microarray technology (SoilChips)	496:539	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31822723	9	50	theme	biogeochemical	1398:1411	arg1	transformation					1413:1426	biogeochemical transformation	1398:1426	biogeochemical transformation of OM	1398:1432	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	5	51	theme	Dissolved	696:704	arg1	matter					714:719	Dissolved organic matter	696:719	Dissolved organic matter from the original soil	696:742	Dissolved organic matter from the original soil was added on the SoilChips to mimic SWI processes.
31822723	1	52	theme	soil-water	152:161	arg1	interfaces					163:172	The soil-water interfaces	148:172	The soil-water interfaces (SWI) in soil pores	148:192	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	1	52	theme	soil-water	152:161	arg1	hotspots					198:205	hotspots	198:205	hotspots for organic matter (OM) transformation	198:244	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	1	52	theme	soil-water	152:161	arg1	SWI					175:177	SWI	175:177	SWI	175:177	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	5	53	theme	organic	706:712	arg1	matter					714:719	Dissolved organic matter	696:719	Dissolved organic matter from the original soil	696:742	Dissolved organic matter from the original soil was added on the SoilChips to mimic SWI processes.
31822723	9	54	theme	direct	1378:1383	arg1	insight					1385:1391	a direct insight	1376:1391	a direct insight into biogeochemical transformation of OM	1376:1432	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	7	55	theme	OM	980:981	arg1	coatings					983:990	OM coatings	980:990	OM coatings	980:990	Over 21 days, ammonium addition increased OM coatings at SWIs and modified the OM chemical structure with more alcoholic- and carboxylic-C compared to the unfertilized control.
31822723	6	56	theme	kg-1	842:845	arg1	soil					847:850	90 mg N kg-1 soil	834:850	90 mg N kg-1 soil	834:850	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	6	56	theme	kg-1	842:845	arg1	fertilization					819:831	ammonium fertilization	810:831	ammonium fertilization (90 mg N kg-1 soil)	810:851	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	2	57	theme	direct	325:330	arg1	tracing					347:353	direct and continuous tracing	325:353	direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations,	325:452	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	9	58	theme	OM	1431:1432	arg1	transformation					1413:1426	biogeochemical transformation	1398:1426	biogeochemical transformation of OM	1398:1432	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	0	59	theme	biogeochemical	77:90	arg1	interfaces					92:101	soil biogeochemical interfaces	72:101	soil biogeochemical interfaces	72:101	Nitrogen fertilization modifies organic transformations and coatings on soil biogeochemical interfaces through microbial polysaccharides synthesis.
31822723	6	60	theme	90 mg N	834:840	arg1	soil					847:850	90 mg N kg-1 soil	834:850	90 mg N kg-1 soil	834:850	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	6	60	theme	90 mg N	834:840	arg1	fertilization					819:831	ammonium fertilization	810:831	ammonium fertilization (90 mg N kg-1 soil)	810:851	The effects of ammonium fertilization (90 mg N kg-1 soil) on chemical composition of SWIs were evaluated via X-ray photoelectron spectroscopy.
31822723	1	61	theme	organic	211:217	arg1	matter					219:224	organic matter	211:224	organic matter (OM) transformation	211:244	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	1	61	theme	organic	211:217	arg1	OM					227:228	OM	227:228	OM	227:228	The soil-water interfaces (SWI) in soil pores are hotspots for organic matter (OM) transformation.
31822723	4	62	theme	dispersed	636:644	arg1	suspension					663:672	a dispersed Oxisol A horizon suspension	634:672	a dispersed Oxisol A horizon suspension	634:672	Homogeneous 800-μm-diameter SoilChips were constructed by depositing a dispersed Oxisol A horizon suspension on a patterned glass.
31822723	0	63	theme	soil	72:75	arg1	interfaces					92:101	soil biogeochemical interfaces	72:101	soil biogeochemical interfaces	72:101	Nitrogen fertilization modifies organic transformations and coatings on soil biogeochemical interfaces through microbial polysaccharides synthesis.
31822723	9	64	theme	molecular	1305:1313	arg1	processing					1315:1324	the specific OM molecular processing	1289:1324	the specific OM molecular processing	1289:1324	We demonstrated that N availability modifies the specific OM molecular processing and its immobilization on SWIs, thereby providing a direct insight into biogeochemical transformation of OM at micro-scale.
31822723	4	65	theme	A	653:653	arg1	suspension					663:672	a dispersed Oxisol A horizon suspension	634:672	a dispersed Oxisol A horizon suspension	634:672	Homogeneous 800-μm-diameter SoilChips were constructed by depositing a dispersed Oxisol A horizon suspension on a patterned glass.
31822723	2	66	theme	reactions	370:378	arg1	tracing					347:353	direct and continuous tracing	325:353	direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations,	325:452	However, due to the heterogeneous and opaque nature of soil microenvironment, direct and continuous tracing of interfacial reactions, such as OM transformations and formation of organo-mineral associations, are rare.
31822723	3	67	theme	new	498:500	arg1	SoilChips					530:538	SoilChips	530:538	SoilChips	530:538	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31822723	3	67	theme	new	498:500	arg1	technology					518:527	a new soil microarray technology	496:527	a new soil microarray technology (SoilChips)	496:539	To investigate these processes, a new soil microarray technology (SoilChips) was developed and used.
31216277	6	0	theme	broiler	1086:1092	arg1	chickens					1094:1101	the broiler chickens	1082:1101	the broiler chickens	1082:1101	Lysozyme administration did not contribute significantly (P > 0.05) to the growth of the broiler chickens.
31216277	2	1	theme	bacterial	354:362	arg1	strains					364:370	antibiotic-resistant bacterial strains	333:370	antibiotic-resistant bacterial strains	333:370	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	8	2	theme	substrate	1472:1480	arg1	transport					1482:1490	cross-cell substrate transport	1461:1490	cross-cell substrate transport	1461:1490	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	7	3	theme	diet	1268:1271	arg1	groups					1273:1278	the different diet groups	1254:1278	the different diet groups	1254:1278	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	7	4	theme	cecal	1222:1226	arg1	microbiota					1228:1237	the cecal microbiota	1218:1237	the cecal microbiota of chickens in the different diet groups	1218:1278	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	8	5	theme	bacterial	1419:1427	arg1	membranes					1435:1443	bacterial outer membranes	1419:1443	bacterial outer membranes	1419:1443	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	9	6	theme	polysaccharide	1691:1704	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	6	theme	polysaccharide	1691:1704	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	2	7	theme	antibiotic	257:266	arg1	promoters					275:283	antibiotic growth promoters	257:283	antibiotic growth promoters	257:283	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	8	8	theme	carbohydrate	1497:1508	arg1	processes					1520:1528	carbohydrate metabolic processes	1497:1528	carbohydrate metabolic processes	1497:1528	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	7	9	theme	chickens	1242:1249	arg1	microbiota					1228:1237	the cecal microbiota	1218:1237	the cecal microbiota of chickens in the different diet groups	1218:1278	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	7	10	theme	fungal	1196:1201	arg1	communities					1203:1213	the bacterial and fungal communities	1178:1213	the bacterial and fungal communities	1178:1213	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	9	11	theme	genes	1712:1716	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	%					1784:1784	8.8%	1781:1784	8.8% of auxiliary activity genes (705-1,000)	1781:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	%					1885:1885	13.9%	1881:1885	13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1881:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	genes					1856:1860	glycosyltransferase genes	1836:1860	glycosyltransferase genes (5,301-6,844)	1836:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	17,681-24,590					1666:1678	17,681-24,590	1666:1678	17,681-24,590	1666:1678	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	5,301-6,844					1863:1873	5,301-6,844	1863:1873	5,301-6,844	1863:1873	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	%					1634:1634	31.9%	1630:1634	31.9% of glycoside hydrolase genes (17,681-24,590)	1630:1679	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	%					1733:1733	20.7%	1729:1733	20.7% of carbohydrate esterase genes (3,509-4,101)	1729:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	%					1831:1831	16.2%	1827:1831	16.2% of glycosyltransferase genes (5,301-6,844)	1827:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	11	theme	genes	1712:1716	arg1	%					1686:1686	26.1%	1682:1686	26.1% of polysaccharide lyase genes (479-675)	1682:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	3	12	used	used	532:535	arg2	we					529:530	we	529:530	we	529:530	Here, we used the 16S rRNA gene and ITS fragment Illumina sequencing combined with transcriptomic analysis to address this issue.
31216277	4	13	dep	four	749:752	arg1	replicates					754:763	replicates	754:763	replicates	754:763	A total of 400 1-d-old Di Gao chicks were allocated randomly to five groups, each consisting of four replicates (20 birds/group).
31216277	7	14	theme	bacterial	1182:1190	arg1	communities					1203:1213	the bacterial and fungal communities	1178:1213	the bacterial and fungal communities	1178:1213	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	9	15	theme	module	1911:1916	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	15	theme	module	1911:1916	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	0	16	theme	broiler	106:112	arg1	chickens					114:121	broiler chickens	106:121	broiler chickens	106:121	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	5	17	theme	ppm	914:916	arg1	lysozyme					927:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	3	18	theme	16S	541:543	arg1	gene					550:553	the 16S rRNA gene	537:553	the 16S rRNA gene	537:553	Here, we used the 16S rRNA gene and ITS fragment Illumina sequencing combined with transcriptomic analysis to address this issue.
31216277	10	19	theme	polysaccharides	2035:2049	arg1	breakdown					2011:2019	the breakdown	2007:2019	the breakdown of non-starch polysaccharides in the cecum	2007:2062	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	0	20	from	function	70:77	arg1	chickens					114:121	broiler chickens	106:121	broiler chickens	106:121	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	3	21	theme	Illumina	572:579	arg1	sequencing					581:590	ITS fragment Illumina sequencing	559:590	ITS fragment Illumina sequencing	559:590	Here, we used the 16S rRNA gene and ITS fragment Illumina sequencing combined with transcriptomic analysis to address this issue.
31216277	7	22	dep	diversity	1149:1157	arg1	the					1145:1147	the	1145:1147	the	1145:1147	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	0	23	from	structure	56:64	arg1	chickens					114:121	broiler chickens	106:121	broiler chickens	106:121	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	6	24	theme	P	1055:1055	arg1	>					1057:1057	P > 0.05	1055:1062	P > 0.05	1055:1062	Lysozyme administration did not contribute significantly (P > 0.05) to the growth of the broiler chickens.
31216277	4	25	theme	chicks	683:688	arg1	total					655:659	A total	653:659	A total of 400 1-d-old Di Gao chicks	653:688	A total of 400 1-d-old Di Gao chicks were allocated randomly to five groups, each consisting of four replicates (20 birds/group).
31216277	8	26	theme	cecal	1559:1563	arg1	carbon					1576:1581	the cecal microbiota carbon	1555:1581	the cecal microbiota carbon	1555:1581	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	9	27	theme	carbohydrate	1738:1749	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	27	theme	carbohydrate	1738:1749	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	8	28	dep	significant	1335:1345	arg1	<					1350:1350	P < 0.05	1348:1355	P < 0.05	1348:1355	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	3	29	theme	transcriptomic	606:619	arg1	analysis					621:628	transcriptomic analysis	606:628	transcriptomic analysis	606:628	Here, we used the 16S rRNA gene and ITS fragment Illumina sequencing combined with transcriptomic analysis to address this issue.
31216277	2	30	theme	gut	492:494	arg1	microbiota					496:505	the chicken gut microbiota	480:505	the chicken gut microbiota	480:505	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	9	31	theme	genes	1760:1764	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	%					1784:1784	8.8%	1781:1784	8.8% of auxiliary activity genes (705-1,000)	1781:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	%					1885:1885	13.9%	1881:1885	13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1881:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	genes					1856:1860	glycosyltransferase genes	1836:1860	glycosyltransferase genes (5,301-6,844)	1836:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	17,681-24,590					1666:1678	17,681-24,590	1666:1678	17,681-24,590	1666:1678	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	5,301-6,844					1863:1873	5,301-6,844	1863:1873	5,301-6,844	1863:1873	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	%					1634:1634	31.9%	1630:1634	31.9% of glycoside hydrolase genes (17,681-24,590)	1630:1679	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	%					1733:1733	20.7%	1729:1733	20.7% of carbohydrate esterase genes (3,509-4,101)	1729:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	%					1831:1831	16.2%	1827:1831	16.2% of glycosyltransferase genes (5,301-6,844)	1827:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	31	theme	genes	1760:1764	arg1	%					1686:1686	26.1%	1682:1686	26.1% of polysaccharide lyase genes (479-675)	1682:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	32	theme	cecal	1956:1960	arg1	samples					1962:1968	the cecal samples	1952:1968	the cecal samples	1952:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	8	33	theme	energy	1587:1592	arg1	metabolism					1594:1603	energy metabolism	1587:1603	energy metabolism	1587:1603	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	10	34	from	players	1996:2002	arg1	breakdown					2011:2019	the breakdown	2007:2019	the breakdown of non-starch polysaccharides in the cecum	2007:2062	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	5	35	theme	grower	828:833	arg1	diet					845:848	a starter (1-21 d) and a grower (22-42 d) diet	803:848	a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin	803:957	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	5	35	theme	grower	828:833	arg1	chicks					787:792	The chicks	783:792	The chicks	783:792	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	5	35	theme	grower	828:833	arg1	control					976:982	an antibiotic control	962:982	an antibiotic control for 6 weeks	962:994	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	0	36	from	Effects	0:6	arg1	function					70:77	function	70:77	function	70:77	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	0	36	from	Effects	0:6	arg1	structure					56:64	structure	56:64	structure	56:64	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	5	37	theme	0	868:868	arg1	lysozyme					927:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	7	38	from	differences	1130:1140	arg1	composition					1163:1173	composition	1163:1173	composition	1163:1173	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	7	38	from	differences	1130:1140	arg1	diversity					1149:1157	diversity	1149:1157	diversity	1149:1157	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	7	38	from	differences	1130:1140	arg1	microbiota					1228:1237	the cecal microbiota	1218:1237	the cecal microbiota of chickens in the different diet groups	1218:1278	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	8	39	theme	lysozyme	1301:1308	arg1	supplementation					1310:1324	lysozyme supplementation	1301:1324	lysozyme supplementation	1301:1324	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	0	40	theme	microbiota	92:101	arg1	function					70:77	function	70:77	function	70:77	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	0	40	theme	microbiota	92:101	arg1	structure					56:64	structure	56:64	structure	56:64	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	9	41	theme	auxiliary	1789:1797	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	41	theme	auxiliary	1789:1797	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	2	42	dep	composition	437:447	arg1	the					433:435	the	433:435	the	433:435	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	9	43	theme	genes	1808:1812	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	%					1784:1784	8.8%	1781:1784	8.8% of auxiliary activity genes (705-1,000)	1781:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	%					1885:1885	13.9%	1881:1885	13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1881:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	genes					1856:1860	glycosyltransferase genes	1836:1860	glycosyltransferase genes (5,301-6,844)	1836:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	17,681-24,590					1666:1678	17,681-24,590	1666:1678	17,681-24,590	1666:1678	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	5,301-6,844					1863:1873	5,301-6,844	1863:1873	5,301-6,844	1863:1873	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	%					1634:1634	31.9%	1630:1634	31.9% of glycoside hydrolase genes (17,681-24,590)	1630:1679	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	%					1733:1733	20.7%	1729:1733	20.7% of carbohydrate esterase genes (3,509-4,101)	1729:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	%					1831:1831	16.2%	1827:1831	16.2% of glycosyltransferase genes (5,301-6,844)	1827:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	43	theme	genes	1808:1812	arg1	%					1686:1686	26.1%	1682:1686	26.1% of polysaccharide lyase genes (479-675)	1682:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	2	44	theme	supplementation	414:428	arg1	effects					394:400	the effects	390:400	the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota	390:505	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	0	45	theme	dietary	11:17	arg1	supplementation					19:33	dietary supplementation	11:33	dietary supplementation with lysozyme	11:47	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	0	46	dep	structure	56:64	arg1	the					52:54	the	52:54	the	52:54	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	5	47	theme	starter	805:811	arg1	diet					845:848	a starter (1-21 d) and a grower (22-42 d) diet	803:848	a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin	803:957	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	5	47	theme	starter	805:811	arg1	chicks					787:792	The chicks	783:792	The chicks	783:792	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	5	47	theme	starter	805:811	arg1	control					976:982	an antibiotic control	962:982	an antibiotic control for 6 weeks	962:994	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	5	48	theme	antibiotic	965:974	arg1	chicks					787:792	The chicks	783:792	The chicks	783:792	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	5	48	theme	antibiotic	965:974	arg1	diet					845:848	a starter (1-21 d) and a grower (22-42 d) diet	803:848	a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin	803:957	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	5	48	theme	antibiotic	965:974	arg1	control					976:982	an antibiotic control	962:982	an antibiotic control for 6 weeks	962:994	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	2	49	theme	antibiotic-resistant	333:352	arg1	strains					364:370	antibiotic-resistant bacterial strains	333:370	antibiotic-resistant bacterial strains	333:370	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	5	50	theme	LYS100	898:903	arg1	lysozyme					927:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	9	51	theme	hydrolase	1649:1657	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	10	52	from	breakdown	2011:2019	arg1	cecum					2058:2062	the cecum	2054:2062	the cecum	2054:2062	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	2	53	theme	emergence	320:328	arg1	risk					308:311	the associated risk	293:311	the associated risk of the emergence of antibiotic-resistant bacterial strains	293:370	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	8	54	theme	outer	1429:1433	arg1	membranes					1435:1443	bacterial outer membranes	1419:1443	bacterial outer membranes	1419:1443	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	9	55	theme	glycosyltransferase	1836:1854	arg1	5,301-6,844					1863:1873	5,301-6,844	1863:1873	5,301-6,844	1863:1873	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	55	theme	glycosyltransferase	1836:1854	arg1	genes					1856:1860	glycosyltransferase genes	1836:1860	glycosyltransferase genes (5,301-6,844)	1836:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	6	56	theme	chickens	1094:1101	arg1	growth					1072:1077	the growth	1068:1077	the growth of the broiler chickens	1068:1101	Lysozyme administration did not contribute significantly (P > 0.05) to the growth of the broiler chickens.
31216277	2	57	theme	strains	364:370	arg1	emergence					320:328	the emergence	316:328	the emergence of antibiotic-resistant bacterial strains	316:370	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	8	58	theme	walls	1454:1458	arg1	synthesis/degradation					1394:1414	the synthesis/degradation	1390:1414	the synthesis/degradation of bacterial outer membranes and cell walls	1390:1458	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	8	58	theme	walls	1454:1458	arg1	transport					1482:1490	cross-cell substrate transport	1461:1490	cross-cell substrate transport	1461:1490	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	8	58	theme	walls	1454:1458	arg1	processes					1520:1528	carbohydrate metabolic processes	1497:1528	carbohydrate metabolic processes	1497:1528	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	7	59	theme	different	1258:1266	arg1	groups					1273:1278	the different diet groups	1254:1278	the different diet groups	1254:1278	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	10	60	theme	main	1991:1994	arg1	players					1996:2002	the main players	1987:2002	the main players in the breakdown of non-starch polysaccharides in the cecum	1987:2062	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	10	60	theme	main	1991:1994	arg1	they					1977:1980	they	1977:1980	they	1977:1980	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	8	61	theme	cross-cell	1461:1470	arg1	transport					1482:1490	cross-cell substrate transport	1461:1490	cross-cell substrate transport	1461:1490	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	6	62	theme	Lysozyme	997:1004	arg1	administration					1006:1019	Lysozyme administration	997:1019	Lysozyme administration	997:1019	Lysozyme administration did not contribute significantly (P > 0.05) to the growth of the broiler chickens.
31216277	2	63	theme	growth	268:273	arg1	promoters					275:283	antibiotic growth promoters	257:283	antibiotic growth promoters	257:283	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	1	64	theme	intestinal	155:164	arg1	pathogens					166:174	intestinal pathogens	155:174	intestinal pathogens in poultry	155:185	Lysozyme is known to eliminate intestinal pathogens in poultry and improve their growth performance.
31216277	9	65	theme	lyase	1706:1710	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	65	theme	lyase	1706:1710	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	3	66	theme	rRNA	545:548	arg1	gene					550:553	the 16S rRNA gene	537:553	the 16S rRNA gene	537:553	Here, we used the 16S rRNA gene and ITS fragment Illumina sequencing combined with transcriptomic analysis to address this issue.
31216277	7	67	theme	communities	1203:1213	arg1	composition					1163:1173	composition	1163:1173	composition	1163:1173	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	7	67	theme	communities	1203:1213	arg1	diversity					1149:1157	diversity	1149:1157	diversity	1149:1157	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	9	68	theme	carbohydrate-binding	1890:1909	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	68	theme	carbohydrate-binding	1890:1909	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	2	69	theme	associated	297:306	arg1	risk					308:311	the associated risk	293:311	the associated risk of the emergence of antibiotic-resistant bacterial strains	293:370	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	8	70	theme	metabolic	1510:1518	arg1	processes					1520:1528	carbohydrate metabolic processes	1497:1528	carbohydrate metabolic processes	1497:1528	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	9	71	theme	genes	1918:1922	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	%					1784:1784	8.8%	1781:1784	8.8% of auxiliary activity genes (705-1,000)	1781:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	%					1885:1885	13.9%	1881:1885	13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1881:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	genes					1856:1860	glycosyltransferase genes	1836:1860	glycosyltransferase genes (5,301-6,844)	1836:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	17,681-24,590					1666:1678	17,681-24,590	1666:1678	17,681-24,590	1666:1678	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	5,301-6,844					1863:1873	5,301-6,844	1863:1873	5,301-6,844	1863:1873	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	%					1634:1634	31.9%	1630:1634	31.9% of glycoside hydrolase genes (17,681-24,590)	1630:1679	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	%					1733:1733	20.7%	1729:1733	20.7% of carbohydrate esterase genes (3,509-4,101)	1729:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	%					1831:1831	16.2%	1827:1831	16.2% of glycosyltransferase genes (5,301-6,844)	1827:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	71	theme	genes	1918:1922	arg1	%					1686:1686	26.1%	1682:1686	26.1% of polysaccharide lyase genes (479-675)	1682:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	3	72	theme	fragment	563:570	arg1	sequencing					581:590	ITS fragment Illumina sequencing	559:590	ITS fragment Illumina sequencing	559:590	Here, we used the 16S rRNA gene and ITS fragment Illumina sequencing combined with transcriptomic analysis to address this issue.
31216277	10	73	theme	non-starch	2024:2033	arg1	polysaccharides					2035:2049	non-starch polysaccharides	2024:2049	non-starch polysaccharides	2024:2049	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	4	74	theme	Gao	679:681	arg1	chicks					683:688	400 1-d-old Di Gao chicks	664:688	400 1-d-old Di Gao chicks	664:688	A total of 400 1-d-old Di Gao chicks were allocated randomly to five groups, each consisting of four replicates (20 birds/group).
31216277	10	75	dep	Megamonas	2198:2206	arg1	Clostridium					2114:2124	Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas	2102:2206	Clostridium	2114:2124	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	10	75	dep	Megamonas	2198:2206	arg1	Barnesiella					2141:2151	Barnesiella	2141:2151	Barnesiella	2141:2151	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	10	75	dep	Megamonas	2198:2206	arg1	Blastocystis					2127:2138	Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas	2102:2206	Blastocystis	2127:2138	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	10	76	dep	Akkermansia	2268:2278	arg1	Bifidobacterium					2251:2265	Paenibacillus, Bifidobacterium, Akkermansia	2236:2278	Bifidobacterium	2251:2265	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	9	77	theme	esterase	1751:1758	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	77	theme	esterase	1751:1758	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	6	78	dep	contribute	1029:1038	arg1	>					1057:1057	P > 0.05	1055:1062	P > 0.05	1055:1062	Lysozyme administration did not contribute significantly (P > 0.05) to the growth of the broiler chickens.
31216277	8	79	theme	microbiota	1565:1574	arg1	carbon					1576:1581	the cecal microbiota carbon	1555:1581	the cecal microbiota carbon	1555:1581	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	2	80	theme	chicken	484:490	arg1	microbiota					496:505	the chicken gut microbiota	480:505	the chicken gut microbiota	480:505	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	10	81	theme	other	2285:2289	arg1	bacteria					2291:2298	other bacteria	2285:2298	other bacteria	2285:2298	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	1	82	from	pathogens	166:174	arg1	poultry					179:185	poultry	179:185	poultry	179:185	Lysozyme is known to eliminate intestinal pathogens in poultry and improve their growth performance.
31216277	4	83	theme	1-d-old	668:674	arg1	chicks					683:688	400 1-d-old Di Gao chicks	664:688	400 1-d-old Di Gao chicks	664:688	A total of 400 1-d-old Di Gao chicks were allocated randomly to five groups, each consisting of four replicates (20 birds/group).
31216277	0	84	theme	cecal	86:90	arg1	microbiota					92:101	the cecal microbiota	82:101	the cecal microbiota	82:101	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	7	85	from	microbiota	1228:1237	arg1	groups					1273:1278	the different diet groups	1254:1278	the different diet groups	1254:1278	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	2	86	theme	microbiota	496:505	arg1	composition					437:447	composition	437:447	composition	437:447	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	2	86	theme	microbiota	496:505	arg1	biodiversity					450:461	biodiversity	450:461	biodiversity	450:461	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	2	86	theme	microbiota	496:505	arg1	function					468:475	function	468:475	function	468:475	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	7	87	theme	P	1120:1120	arg1	>					1122:1122	P > 0.05	1120:1127	P > 0.05	1120:1127	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	8	88	theme	significant	1335:1345	arg1	enrichment					1358:1367	a significant (P < 0.05) enrichment	1333:1367	a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes	1333:1528	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	9	89	theme	activity	1799:1806	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	89	theme	activity	1799:1806	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	0	90	theme	supplementation	19:33	arg1	Effects					0:6	Effects	0:6	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.	0:122	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	5	91	theme	LYS40	885:889	arg1	lysozyme					927:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme	868:934	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	7	92	theme	significant	1107:1117	arg1	differences					1130:1140	No significant (P > 0.05) differences	1104:1140	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups	1104:1278	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	8	93	theme	P	1348:1348	arg1	<					1350:1350	P < 0.05	1348:1355	P < 0.05	1348:1355	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	2	94	theme	lysozyme	405:412	arg1	supplementation					414:428	lysozyme supplementation	405:428	lysozyme supplementation	405:428	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	0	95	with	supplementation	19:33	arg1	lysozyme					40:47	lysozyme	40:47	lysozyme	40:47	Effects of dietary supplementation with lysozyme on the structure and function of the cecal microbiota in broiler chickens.
31216277	10	96	dep	Alistipes	2091:2099	arg1	Eubacterium					2209:2219	Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus	2074:2233	Eubacterium	2209:2219	Thus, they were the main players in the breakdown of non-starch polysaccharides in the cecum, although Parabacteroides, Alistipes, Prevotella, Clostridium, Blastocystis, Barnesiella, Blautia, Faecalibacterium, Subdoligranulum, Megamonas, Eubacterium, Ruminococcus, Paenibacillus, Bifidobacterium, Akkermansia, and other bacteria also participated.
31216277	9	97	theme	glycoside	1639:1647	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	5	98	dep	lysozyme	927:934	arg1	flavomycin					948:957	flavomycin	948:957	flavomycin	948:957	The chicks were fed a starter (1-21 d) and a grower (22-42 d) diet supplemented with 0 (control), 40 (LYS40), 100 (LYS100), or 200 ppm (LYS200) lysozyme, or 400 ppm flavomycin as an antibiotic control for 6 weeks.
31216277	8	99	theme	membranes	1435:1443	arg1	synthesis/degradation					1394:1414	the synthesis/degradation	1390:1414	the synthesis/degradation of bacterial outer membranes and cell walls	1390:1458	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	8	99	theme	membranes	1435:1443	arg1	transport					1482:1490	cross-cell substrate transport	1461:1490	cross-cell substrate transport	1461:1490	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	8	99	theme	membranes	1435:1443	arg1	processes					1520:1528	carbohydrate metabolic processes	1497:1528	carbohydrate metabolic processes	1497:1528	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	9	100	theme	genes	1659:1663	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	%					1784:1784	8.8%	1781:1784	8.8% of auxiliary activity genes (705-1,000)	1781:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	%					1885:1885	13.9%	1881:1885	13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1881:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	genes					1856:1860	glycosyltransferase genes	1836:1860	glycosyltransferase genes (5,301-6,844)	1836:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	17,681-24,590					1666:1678	17,681-24,590	1666:1678	17,681-24,590	1666:1678	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	5,301-6,844					1863:1873	5,301-6,844	1863:1873	5,301-6,844	1863:1873	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	%					1634:1634	31.9%	1630:1634	31.9% of glycoside hydrolase genes (17,681-24,590)	1630:1679	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	%					1733:1733	20.7%	1729:1733	20.7% of carbohydrate esterase genes (3,509-4,101)	1729:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	%					1831:1831	16.2%	1827:1831	16.2% of glycosyltransferase genes (5,301-6,844)	1827:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	100	theme	genes	1659:1663	arg1	%					1686:1686	26.1%	1682:1686	26.1% of polysaccharide lyase genes (479-675)	1682:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	8	101	theme	genes	1372:1376	arg1	enrichment					1358:1367	a significant (P < 0.05) enrichment	1333:1367	a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes	1333:1528	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	8	102	theme	cell	1449:1452	arg1	walls					1454:1458	cell walls	1449:1458	cell walls	1449:1458	However, lysozyme supplementation led to a significant (P < 0.05) enrichment of genes involved in the synthesis/degradation of bacterial outer membranes and cell walls, cross-cell substrate transport, and carbohydrate metabolic processes, thus possibly promoting the cecal microbiota carbon and energy metabolism.
31216277	1	103	theme	growth	205:210	arg1	performance					212:222	their growth performance	199:222	their growth performance	199:222	Lysozyme is known to eliminate intestinal pathogens in poultry and improve their growth performance.
31216277	7	104	dep	significant	1107:1117	arg1	>					1122:1122	P > 0.05	1120:1127	P > 0.05	1120:1127	No significant (P > 0.05) differences in the diversity and composition of the bacterial and fungal communities in the cecal microbiota of chickens in the different diet groups were found.
31216277	2	105	from	effects	394:400	arg1	composition					437:447	composition	437:447	composition	437:447	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	2	105	from	effects	394:400	arg1	biodiversity					450:461	biodiversity	450:461	biodiversity	450:461	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	2	105	from	effects	394:400	arg1	function					468:475	function	468:475	function	468:475	However, whether it can replace antibiotic growth promoters without the associated risk of the emergence of antibiotic-resistant bacterial strains is not known, and the effects of lysozyme supplementation on the composition, biodiversity, and function of the chicken gut microbiota remain unclear.
31216277	9	106	theme	genes	1856:1860	arg1	479-675					1719:1725	479-675	1719:1725	479-675	1719:1725	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	%					1784:1784	8.8%	1781:1784	8.8% of auxiliary activity genes (705-1,000)	1781:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	genes					1659:1663	glycoside hydrolase genes	1639:1663	glycoside hydrolase genes	1639:1663	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	%					1885:1885	13.9%	1881:1885	13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1881:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	genes					1760:1764	carbohydrate esterase genes	1738:1764	carbohydrate esterase genes (3,509-4,101)	1738:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	genes					1856:1860	glycosyltransferase genes	1836:1860	glycosyltransferase genes (5,301-6,844)	1836:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	17,681-24,590					1666:1678	17,681-24,590	1666:1678	17,681-24,590	1666:1678	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	3,509-4,101					1767:1777	3,509-4,101	1767:1777	3,509-4,101	1767:1777	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	5,301-6,844					1863:1873	5,301-6,844	1863:1873	5,301-6,844	1863:1873	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	%					1634:1634	31.9%	1630:1634	31.9% of glycoside hydrolase genes (17,681-24,590)	1630:1679	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	genes					1712:1716	polysaccharide lyase genes	1691:1716	polysaccharide lyase genes (479-675)	1691:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	%					1733:1733	20.7%	1729:1733	20.7% of carbohydrate esterase genes (3,509-4,101)	1729:1778	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	705-1,000					1815:1823	705-1,000	1815:1823	705-1,000	1815:1823	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	genes					1808:1812	auxiliary activity genes	1789:1812	auxiliary activity genes (705-1,000)	1789:1824	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	%					1831:1831	16.2%	1827:1831	16.2% of glycosyltransferase genes (5,301-6,844)	1827:1874	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	genes					1918:1922	carbohydrate-binding module genes	1890:1922	carbohydrate-binding module genes (8838-15,172) identified in the cecal samples	1890:1968	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	8838-15,172					1925:1935	8838-15,172	1925:1935	8838-15,172	1925:1935	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
31216277	9	106	theme	genes	1856:1860	arg1	%					1686:1686	26.1%	1682:1686	26.1% of polysaccharide lyase genes (479-675)	1682:1726	Bacteroides contributed 31.9% of glycoside hydrolase genes (17,681-24,590), 26.1% of polysaccharide lyase genes (479-675), 20.7% of carbohydrate esterase genes (3,509-4,101), 8.8% of auxiliary activity genes (705-1,000), 16.2% of glycosyltransferase genes (5,301-6,844), and 13.9% of carbohydrate-binding module genes (8838-15,172) identified in the cecal samples.
29385488	12	0	theme	DM	2091:2092	arg1	IVATTD					2081:2086	IVATTD	2081:2086	IVATTD	2081:2086	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	0	theme	DM	2091:2092	arg1	correlations					1995:2006	The stronger correlations	1982:2006	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides	1982:2065	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	0	theme	DM	2091:2092	arg1	IVAID					2071:2075	IVAID	2071:2075	IVAID	2071:2075	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	14	1	theme	physical	2597:2604	arg1	characteristics					2606:2620	the physical characteristics	2593:2620	the physical characteristics of feed ingredients	2593:2640	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	11	2	theme	fiber	1941:1945	arg1	concentration					1858:1870	the concentration	1854:1870	the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber	1854:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	2	theme	fiber	1941:1945	arg1	IVATTD					1961:1966	IVATTD	1961:1966	IVATTD	1961:1966	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	2	theme	fiber	1941:1945	arg1	IVAID					1951:1955	IVAID	1951:1955	IVAID	1951:1955	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	12	3	theme	DM	2265:2266	arg1	digestibility					2248:2260	the digestibility	2244:2260	the digestibility of DM and OM	2244:2273	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	2	4	theme	beet	664:667	arg1	SBP					675:677	SBP	675:677	SBP	675:677	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	4	theme	beet	664:667	arg1	pulp					669:672	sugar beet pulp	658:672	sugar beet pulp (SBP)	658:678	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	4	theme	beet	664:667	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	0	5	theme	matter	207:212	arg1	digestibility					186:198	in vitro digestibility	177:198	in vitro digestibility of dry matter	177:212	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	4	6	theme	water-binding	905:917	arg1	capacity					919:926	water-binding capacity	905:926	water-binding capacity (WBC)	905:932	The physical characteristics measured included bulk density, water-binding capacity (WBC), swelling, and viscosity.
29385488	4	6	theme	water-binding	905:917	arg1	WBC					929:931	WBC	929:931	WBC	929:931	The physical characteristics measured included bulk density, water-binding capacity (WBC), swelling, and viscosity.
29385488	12	7	theme	OM	2272:2273	arg1	digestibility					2248:2260	the digestibility	2244:2260	the digestibility of DM and OM	2244:2273	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	13	8	theme	analyzed	2541:2548	arg1	GE					2550:2551	all analyzed GE	2537:2551	all analyzed GE	2537:2551	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	10	9	dep	ADF	1736:1738	arg1	r					1741:1741	r	1741:1741	r = -0.61	1741:1749	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	12	10	theme	insoluble	2030:2038	arg1	polysaccharides					2051:2065	insoluble non-starch polysaccharides	2030:2065	insoluble non-starch polysaccharides	2030:2065	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	11	theme	feed	2202:2205	arg1	ingredients					2207:2217	feed ingredients	2202:2217	feed ingredients	2202:2217	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	12	theme	digestibility	2248:2260	arg1	concentration					2178:2190	the concentration	2174:2190	the concentration of TDF in feed ingredients	2174:2217	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	12	theme	digestibility	2248:2260	arg1	predictor					2231:2239	a better predictor	2222:2239	a better predictor of the digestibility of DM and OM than values for NDF and ADF	2222:2301	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	11	13	theme	dietary	1933:1939	arg1	fiber					1941:1945	soluble dietary fiber	1925:1945	soluble dietary fiber	1925:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	6	14	theme	ingredients	1125:1135	arg1	composition					1105:1115	the analyzed chemical composition	1083:1115	the analyzed chemical composition of most ingredients	1083:1135	Results indicated that the analyzed chemical composition of most ingredients added to 100% or greater, except for DDGS, SBP, and SF, where nutrients added to only 94.29%, 88.90%, and 96.09%, respectively.
29385488	11	15	theme	ether	1899:1903	arg1	extract					1905:1911	acid-hydrolyzed ether extract	1883:1911	acid-hydrolyzed ether extract	1883:1911	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	0	16	theme	physical	137:144	arg1	characteristics					146:160	physical characteristics	137:160	physical characteristics	137:160	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	1	17	theme	total	389:393	arg1	IVATTD					416:421	IVATTD	416:421	IVATTD	416:421	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	17	theme	total	389:393	arg1	digestibility					401:413	in vitro apparent total tract digestibility	371:413	in vitro apparent total tract digestibility (IVATTD)	371:422	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	8	18	theme	DM	1527:1528	arg1	IVAID					1508:1512	IVAID	1508:1512	IVAID	1508:1512	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	18	theme	DM	1527:1528	arg1	WBC					1486:1488	WBC	1486:1488	WBC	1486:1488	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	18	theme	DM	1527:1528	arg1	viscosity					1494:1502	viscosity	1494:1502	viscosity	1494:1502	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	18	theme	DM	1527:1528	arg1	swelling					1476:1483	swelling	1476:1483	swelling	1476:1483	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	18	theme	DM	1527:1528	arg1	IVATTD					1517:1522	IVATTD	1517:1522	IVATTD	1517:1522	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	2	19	theme	corn	625:628	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	19	theme	corn	625:628	arg1	meal					635:638	corn germ meal	625:638	corn germ meal	625:638	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	8	20	theme	OM	1533:1534	arg1	IVAID					1508:1512	IVAID	1508:1512	IVAID	1508:1512	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	20	theme	OM	1533:1534	arg1	WBC					1486:1488	WBC	1486:1488	WBC	1486:1488	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	20	theme	OM	1533:1534	arg1	viscosity					1494:1502	viscosity	1494:1502	viscosity	1494:1502	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	20	theme	OM	1533:1534	arg1	swelling					1476:1483	swelling	1476:1483	swelling	1476:1483	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	8	20	theme	OM	1533:1534	arg1	IVATTD					1517:1522	IVATTD	1517:1522	IVATTD	1517:1522	No correlation was observed between swelling, WBC, or viscosity and IVAID or IVATTD of DM or OM.
29385488	12	21	theme	better	2224:2229	arg1	concentration					2178:2190	the concentration	2174:2190	the concentration of TDF in feed ingredients	2174:2217	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	21	theme	better	2224:2229	arg1	predictor					2231:2239	a better predictor	2222:2239	a better predictor of the digestibility of DM and OM than values for NDF and ADF	2222:2301	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	6	22	theme	chemical	1096:1103	arg1	composition					1105:1115	the analyzed chemical composition	1083:1115	the analyzed chemical composition of most ingredients	1083:1135	Results indicated that the analyzed chemical composition of most ingredients added to 100% or greater, except for DDGS, SBP, and SF, where nutrients added to only 94.29%, 88.90%, and 96.09%, respectively.
29385488	14	23	theme	feed	2700:2703	arg1	ingredients					2705:2715	feed ingredients	2700:2715	feed ingredients	2700:2715	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	4	24	theme	physical	848:855	arg1	characteristics					857:871	The physical characteristics	844:871	The physical characteristics measured	844:880	The physical characteristics measured included bulk density, water-binding capacity (WBC), swelling, and viscosity.
29385488	12	25	theme	OM	2098:2099	arg1	IVATTD					2081:2086	IVATTD	2081:2086	IVATTD	2081:2086	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	25	theme	OM	2098:2099	arg1	correlations					1995:2006	The stronger correlations	1982:2006	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides	1982:2065	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	25	theme	OM	2098:2099	arg1	IVAID					2071:2075	IVAID	2071:2075	IVAID	2071:2075	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	2	26	theme	copra	641:645	arg1	expellers					647:655	copra expellers	641:655	copra expellers	641:655	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	1	27	theme	apparent	330:337	arg1	digestibility					345:357	apparent ileal digestibility	330:357	apparent ileal digestibility (IVAID)	330:365	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	27	theme	apparent	330:337	arg1	IVAID					360:364	IVAID	360:364	IVAID	360:364	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	2	28	dep	distillers	579:588	arg1	grains					596:601	dried grains	590:601	distillers dried grains with solubles (DDGS)	579:622	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	10	29	theme	DM	1805:1806	arg1	IVAID					1796:1800	IVAID	1796:1800	IVAID of DM	1796:1806	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	0	30	theme	energy-contributing	77:95	arg1	nutrients					97:105	all energy-contributing nutrients	73:105	all energy-contributing nutrients	73:105	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	2	31	theme	dried	590:594	arg1	grains					596:601	dried grains	590:601	distillers dried grains with solubles (DDGS)	579:622	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	10	32	theme	r	1721:1721	arg1	NDF					1716:1718	NDF	1716:1718	NDF (r = -0.60)	1716:1730	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	10	32	theme	r	1721:1721	arg1	-0.60					1725:1729	r = -0.60	1721:1729	r = -0.60	1721:1729	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	5	33	theme	analyzed	964:971	arg1	GE					973:974	The analyzed GE	960:974	The analyzed GE	960:974	The analyzed GE was compared with values for GE calculated from all energy-contributing components.
29385488	14	34	from	IVAID	2667:2671	arg1	ingredients					2705:2715	feed ingredients	2700:2715	feed ingredients	2700:2715	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	7	35	theme	GE	1361:1362	arg1	sum					1292:1294	the sum	1288:1294	the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients	1288:1381	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	2	36	theme	fiber	486:490	arg1	concentration					492:504	fiber concentration	486:504	fiber concentration	486:504	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	0	37	theme	feed	115:118	arg1	ingredients					120:130	some feed ingredients	110:130	some feed ingredients	110:130	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	7	38	from	MJ/kg	1423:1427	arg1	pectin					1432:1437	pectin	1432:1437	pectin	1432:1437	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	14	39	from	IVATTD	2677:2682	arg1	ingredients					2705:2715	feed ingredients	2700:2715	feed ingredients	2700:2715	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	3	40	theme	ingredients	781:791	arg1	IVAID					797:801	IVAID	797:801	IVAID	797:801	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	3	40	theme	ingredients	781:791	arg1	characteristics					762:776	chemical and physical characteristics	740:776	chemical and physical characteristics of ingredients	740:791	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	3	40	theme	ingredients	781:791	arg1	IVATTD					807:812	IVATTD	807:812	IVATTD	807:812	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	9	41	theme	insoluble	1558:1566	arg1	fiber					1576:1580	insoluble dietary fiber	1558:1580	insoluble dietary fiber (IDF)	1558:1586	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	9	41	theme	insoluble	1558:1566	arg1	IDF					1583:1585	IDF	1583:1585	IDF	1583:1585	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	3	42	theme	DM	817:818	arg1	IVAID					797:801	IVAID	797:801	IVAID	797:801	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	3	42	theme	DM	817:818	arg1	characteristics					762:776	chemical and physical characteristics	740:776	chemical and physical characteristics of ingredients	740:791	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	3	42	theme	DM	817:818	arg1	IVATTD					807:812	IVATTD	807:812	IVATTD	807:812	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	9	43	theme	fiber	1576:1580	arg1	concentration					1541:1553	The concentration	1537:1553	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF)	1537:1616	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	11	44	theme	OM	1978:1979	arg1	concentration					1858:1870	the concentration	1854:1870	the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber	1854:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	44	theme	OM	1978:1979	arg1	IVATTD					1961:1966	IVATTD	1961:1966	IVATTD	1961:1966	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	44	theme	OM	1978:1979	arg1	IVAID					1951:1955	IVAID	1951:1955	IVAID	1951:1955	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	0	45	theme	low-molecular-weight	13:32	arg1	carbohydrates					34:46	low-molecular-weight carbohydrates	13:46	low-molecular-weight carbohydrates	13:46	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	1	46	theme	ingredients	292:302	arg1	nutrient					255:262	nutrient	255:262	nutrient	255:262	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	46	theme	ingredients	292:302	arg1	fractions					274:282	fiber fractions	268:282	fiber fractions	268:282	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	13	47	from	agreement	2369:2377	arg1	conclusion					2307:2316	conclusion	2307:2316	conclusion	2307:2316	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	4	48	theme	bulk	891:894	arg1	density					896:902	bulk density	891:902	bulk density	891:902	The physical characteristics measured included bulk density, water-binding capacity (WBC), swelling, and viscosity.
29385488	9	49	theme	P	1645:1645	arg1	<					1647:1647	P < 0.05	1645:1652	P < 0.05	1645:1652	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	7	50	theme	analyzed	1324:1331	arg1	components					1333:1342	the analyzed components	1320:1342	the analyzed components	1320:1342	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	1	51	dep	in	371:372	arg1	vitro					374:378	vitro	374:378	vitro	374:378	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	13	52	theme	analyzed	2388:2395	arg1	GE					2397:2398	the analyzed GE	2384:2398	the analyzed GE	2384:2398	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	3	53	theme	OM	824:825	arg1	IVAID					797:801	IVAID	797:801	IVAID	797:801	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	3	53	theme	OM	824:825	arg1	characteristics					762:776	chemical and physical characteristics	740:776	chemical and physical characteristics of ingredients	740:791	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	3	53	theme	OM	824:825	arg1	IVATTD					807:812	IVATTD	807:812	IVATTD	807:812	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	9	54	theme	dietary	1598:1604	arg1	TDF					1613:1615	TDF	1613:1615	TDF	1613:1615	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	9	54	theme	dietary	1598:1604	arg1	fiber					1606:1610	total dietary fiber	1592:1610	total dietary fiber (TDF)	1592:1616	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	7	55	theme	calculated	1303:1312	arg1	GE					1314:1315	the calculated GE	1299:1315	the calculated GE of the analyzed components	1299:1342	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	11	56	theme	lignin	1914:1919	arg1	concentration					1858:1870	the concentration	1854:1870	the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber	1854:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	56	theme	lignin	1914:1919	arg1	IVATTD					1961:1966	IVATTD	1961:1966	IVATTD	1961:1966	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	56	theme	lignin	1914:1919	arg1	IVAID					1951:1955	IVAID	1951:1955	IVAID	1951:1955	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	57	theme	CP	1875:1876	arg1	concentration					1858:1870	the concentration	1854:1870	the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber	1854:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	57	theme	CP	1875:1876	arg1	IVATTD					1961:1966	IVATTD	1961:1966	IVATTD	1961:1966	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	57	theme	CP	1875:1876	arg1	IVAID					1951:1955	IVAID	1951:1955	IVAID	1951:1955	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	14	58	theme	feed	2625:2628	arg1	ingredients					2630:2640	feed ingredients	2625:2640	feed ingredients	2625:2640	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	10	59	dep	correlated	1769:1778	arg1	<					1783:1783	P < 0.10	1781:1788	P < 0.10	1781:1788	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	10	59	dep	correlated	1769:1778	arg1	tendency					1703:1710	a tendency	1701:1710	a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM	1701:1806	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	12	60	theme	stronger	1986:1993	arg1	correlations					1995:2006	The stronger correlations	1982:2006	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides	1982:2065	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	2	61	with	grains	596:601	arg1	solubles					608:615	solubles	608:615	solubles (DDGS)	608:622	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	61	with	grains	596:601	arg1	DDGS					618:621	DDGS	618:621	DDGS	618:621	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	10	62	dep	=	1743:1743	arg1	-0.61					1745:1749	-0.61	1745:1749	-0.61	1745:1749	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	10	63	theme	=	1743:1743	arg1	r					1741:1741	r	1741:1741	r = -0.61	1741:1749	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	0	64	theme	dry	203:205	arg1	matter					207:212	dry matter	203:212	dry matter	203:212	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	1	65	theme	DM	427:428	arg1	digestibility					345:357	apparent ileal digestibility	330:357	apparent ileal digestibility (IVAID)	330:365	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	65	theme	DM	427:428	arg1	IVATTD					416:421	IVATTD	416:421	IVATTD	416:421	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	65	theme	DM	427:428	arg1	IVAID					360:364	IVAID	360:364	IVAID	360:364	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	65	theme	DM	427:428	arg1	digestibility					401:413	in vitro apparent total tract digestibility	371:413	in vitro apparent total tract digestibility (IVATTD)	371:422	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	14	66	theme	DM	2687:2688	arg1	IVATTD					2677:2682	IVATTD	2677:2682	IVATTD	2677:2682	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	14	66	theme	DM	2687:2688	arg1	IVAID					2667:2671	IVAID	2667:2671	IVAID	2667:2671	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	1	67	theme	fiber	268:272	arg1	fractions					274:282	fiber fractions	268:282	fiber fractions	268:282	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	2	68	theme	soybean	546:552	arg1	SBM					560:562	SBM	560:562	SBM	560:562	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	68	theme	soybean	546:552	arg1	meal					554:557	soybean meal	546:557	soybean meal (SBM)	546:563	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	68	theme	soybean	546:552	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	14	69	used	used	2650:2653	arg2	Concentrations					2554:2567	Concentrations	2554:2567	Concentrations of IDF and TDF	2554:2582	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	14	69	used	used	2650:2653	arg2	characteristics					2606:2620	the physical characteristics	2593:2620	the physical characteristics of feed ingredients	2593:2640	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	11	70	theme	GE	1879:1880	arg1	concentration					1858:1870	the concentration	1854:1870	the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber	1854:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	70	theme	GE	1879:1880	arg1	IVATTD					1961:1966	IVATTD	1961:1966	IVATTD	1961:1966	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	70	theme	GE	1879:1880	arg1	IVAID					1951:1955	IVAID	1951:1955	IVAID	1951:1955	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	1	71	theme	OM	434:435	arg1	digestibility					345:357	apparent ileal digestibility	330:357	apparent ileal digestibility (IVAID)	330:365	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	71	theme	OM	434:435	arg1	IVATTD					416:421	IVATTD	416:421	IVATTD	416:421	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	71	theme	OM	434:435	arg1	IVAID					360:364	IVAID	360:364	IVAID	360:364	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	71	theme	OM	434:435	arg1	digestibility					401:413	in vitro apparent total tract digestibility	371:413	in vitro apparent total tract digestibility (IVATTD)	371:422	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	13	72	theme	ingredients	2350:2360	arg1	GE					2334:2335	the calculated GE	2319:2335	the calculated GE of some feed ingredients	2319:2360	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	2	73	theme	canola	566:571	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	73	theme	canola	566:571	arg1	meal					573:576	canola meal	566:576	canola meal	566:576	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	74	theme	sugar	658:662	arg1	SBP					675:677	SBP	675:677	SBP	675:677	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	74	theme	sugar	658:662	arg1	pulp					669:672	sugar beet pulp	658:672	sugar beet pulp (SBP)	658:678	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	74	theme	sugar	658:662	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	14	75	theme	TDF	2580:2582	arg1	Concentrations					2554:2567	Concentrations	2554:2567	Concentrations of IDF and TDF	2554:2582	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	11	76	theme	extract	1905:1911	arg1	concentration					1858:1870	the concentration	1854:1870	the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber	1854:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	76	theme	extract	1905:1911	arg1	IVATTD					1961:1966	IVATTD	1961:1966	IVATTD	1961:1966	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	76	theme	extract	1905:1911	arg1	IVAID					1951:1955	IVAID	1951:1955	IVAID	1951:1955	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	14	77	theme	IDF	2572:2574	arg1	Concentrations					2554:2567	Concentrations	2554:2567	Concentrations of IDF and TDF	2554:2582	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	10	78	theme	P	1781:1781	arg1	<					1783:1783	P < 0.10	1781:1788	P < 0.10	1781:1788	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	10	78	theme	P	1781:1781	arg1	tendency					1703:1710	a tendency	1701:1710	a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM	1701:1806	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	12	79	theme	non-starch	2040:2049	arg1	polysaccharides					2051:2065	insoluble non-starch polysaccharides	2030:2065	insoluble non-starch polysaccharides	2030:2065	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	1	80	theme	apparent	380:387	arg1	IVATTD					416:421	IVATTD	416:421	IVATTD	416:421	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	80	theme	apparent	380:387	arg1	digestibility					401:413	in vitro apparent total tract digestibility	371:413	in vitro apparent total tract digestibility (IVATTD)	371:422	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	13	81	with	agreement	2369:2377	arg1	GE					2397:2398	the analyzed GE	2384:2398	the analyzed GE	2384:2398	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	6	82	theme	most	1120:1123	arg1	ingredients					1125:1135	most ingredients	1120:1135	most ingredients	1120:1135	Results indicated that the analyzed chemical composition of most ingredients added to 100% or greater, except for DDGS, SBP, and SF, where nutrients added to only 94.29%, 88.90%, and 96.09%, respectively.
29385488	2	83	theme	germ	630:633	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	83	theme	germ	630:633	arg1	meal					635:638	corn germ meal	625:638	corn germ meal	625:638	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	1	84	theme	tract	395:399	arg1	IVATTD					416:421	IVATTD	416:421	IVATTD	416:421	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	84	theme	tract	395:399	arg1	digestibility					401:413	in vitro apparent total tract digestibility	371:413	in vitro apparent total tract digestibility (IVATTD)	371:422	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	0	85	dep	in	177:178	arg1	vitro					180:184	vitro	180:184	vitro	180:184	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	9	86	theme	DM	1680:1681	arg1	IVATTD					1670:1675	IVATTD	1670:1675	IVATTD	1670:1675	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	9	86	theme	DM	1680:1681	arg1	IVAID					1660:1664	IVAID	1660:1664	IVAID	1660:1664	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	0	87	theme	in	177:178	arg1	digestibility					186:198	in vitro digestibility	177:198	in vitro digestibility of dry matter	177:212	Analysis for low-molecular-weight carbohydrates is needed to account for all energy-contributing nutrients in some feed ingredients, but physical characteristics do not predict in vitro digestibility of dry matter.
29385488	11	88	theme	DM	1971:1972	arg1	concentration					1858:1870	the concentration	1854:1870	the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber	1854:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	88	theme	DM	1971:1972	arg1	IVATTD					1961:1966	IVATTD	1961:1966	IVATTD	1961:1966	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	11	88	theme	DM	1971:1972	arg1	IVAID					1951:1955	IVAID	1951:1955	IVAID	1951:1955	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	3	89	theme	chemical	740:747	arg1	characteristics					762:776	chemical and physical characteristics	740:776	chemical and physical characteristics of ingredients	740:791	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	6	90	theme	analyzed	1087:1094	arg1	composition					1105:1115	the analyzed chemical composition	1083:1115	the analyzed chemical composition of most ingredients	1083:1135	Results indicated that the analyzed chemical composition of most ingredients added to 100% or greater, except for DDGS, SBP, and SF, where nutrients added to only 94.29%, 88.90%, and 96.09%, respectively.
29385488	9	91	theme	OM	1687:1688	arg1	IVATTD					1670:1675	IVATTD	1670:1675	IVATTD	1670:1675	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	9	91	theme	OM	1687:1688	arg1	IVAID					1660:1664	IVAID	1660:1664	IVAID	1660:1664	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	14	92	theme	OM	2694:2695	arg1	IVATTD					2677:2682	IVATTD	2677:2682	IVATTD	2677:2682	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	14	92	theme	OM	2694:2695	arg1	IVAID					2667:2671	IVAID	2667:2671	IVAID	2667:2671	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	12	93	from	concentration	2178:2190	arg1	ingredients					2207:2217	feed ingredients	2202:2217	feed ingredients	2202:2217	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	11	94	theme	soluble	1925:1931	arg1	fiber					1941:1945	soluble dietary fiber	1925:1945	soluble dietary fiber	1925:1945	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	7	95	theme	ingredients	1371:1381	arg1	GE					1314:1315	the calculated GE	1299:1315	the calculated GE of the analyzed components	1299:1342	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	7	95	theme	ingredients	1371:1381	arg1	GE					1361:1362	the analyzed GE	1348:1362	the analyzed GE of the ingredients	1348:1381	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	2	96	used	used	527:530	arg2	composition					510:520	composition	510:520	composition	510:520	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	96	used	used	527:530	arg2	concentration					492:504	fiber concentration	486:504	fiber concentration	486:504	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	1	97	from	digestibility	401:413	arg1	ingredient					445:454	each ingredient	440:454	each ingredient	440:454	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	98	theme	ileal	339:343	arg1	digestibility					345:357	apparent ileal digestibility	330:357	apparent ileal digestibility (IVAID)	330:365	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	98	theme	ileal	339:343	arg1	IVAID					360:364	IVAID	360:364	IVAID	360:364	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	7	99	from	MJ/kg	1401:1405	arg1	DDGS					1410:1413	DDGS	1410:1413	DDGS	1410:1413	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	13	100	theme	feed	2345:2348	arg1	ingredients					2350:2360	some feed ingredients	2340:2360	some feed ingredients	2340:2360	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	12	101	theme	DM	2150:2151	arg1	ADF					2114:2116	ADF	2114:2116	ADF	2114:2116	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	101	theme	DM	2150:2151	arg1	IVATTD					2140:2145	IVATTD	2140:2145	IVATTD	2140:2145	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	101	theme	DM	2150:2151	arg1	IVAID					2130:2134	IVAID	2130:2134	IVAID	2130:2134	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	101	theme	DM	2150:2151	arg1	NDF					2122:2124	NDF	2122:2124	NDF	2122:2124	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	10	102	theme	=	1723:1723	arg1	NDF					1716:1718	NDF	1716:1718	NDF (r = -0.60)	1716:1730	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	10	102	theme	=	1723:1723	arg1	-0.60					1725:1729	r = -0.60	1721:1729	r = -0.60	1721:1729	There was a tendency for NDF (r = -0.60) and ADF (r = -0.61) to be negatively correlated (P < 0.10) with IVAID of DM.
29385488	3	103	theme	physical	753:760	arg1	characteristics					762:776	chemical and physical characteristics	740:776	chemical and physical characteristics of ingredients	740:791	Correlations between chemical and physical characteristics of ingredients and IVAID and IVATTD of DM and OM were determined.
29385488	7	104	theme	analyzed	1352:1359	arg1	GE					1361:1362	the analyzed GE	1348:1362	the analyzed GE of the ingredients	1348:1381	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	12	105	theme	OM	2157:2158	arg1	ADF					2114:2116	ADF	2114:2116	ADF	2114:2116	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	105	theme	OM	2157:2158	arg1	IVATTD					2140:2145	IVATTD	2140:2145	IVATTD	2140:2145	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	105	theme	OM	2157:2158	arg1	IVAID					2130:2134	IVAID	2130:2134	IVAID	2130:2134	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	105	theme	OM	2157:2158	arg1	NDF					2122:2124	NDF	2122:2124	NDF	2122:2124	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	11	106	theme	acid-hydrolyzed	1883:1897	arg1	extract					1905:1911	acid-hydrolyzed ether extract	1883:1911	acid-hydrolyzed ether extract	1883:1911	However, no correlation was observed between the concentration of CP, GE, acid-hydrolyzed ether extract, lignin, or soluble dietary fiber and IVAID and IVATTD of DM and OM.
29385488	13	107	theme	calculated	2323:2332	arg1	GE					2334:2335	the calculated GE	2319:2335	the calculated GE of some feed ingredients	2319:2360	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	1	108	theme	in	371:372	arg1	IVATTD					416:421	IVATTD	416:421	IVATTD	416:421	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	108	theme	in	371:372	arg1	digestibility					401:413	in vitro apparent total tract digestibility	371:413	in vitro apparent total tract digestibility (IVATTD)	371:422	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	9	109	dep	correlated	1633:1642	arg1	<					1647:1647	P < 0.05	1645:1652	P < 0.05	1645:1652	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	9	110	theme	dietary	1568:1574	arg1	fiber					1576:1580	insoluble dietary fiber	1558:1580	insoluble dietary fiber (IDF)	1558:1586	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	9	110	theme	dietary	1568:1574	arg1	IDF					1583:1585	IDF	1583:1585	IDF	1583:1585	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	1	111	theme	feed	287:290	arg1	ingredients					292:302	feed ingredients	287:302	feed ingredients	287:302	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	1	112	from	digestibility	345:357	arg1	ingredient					445:454	each ingredient	440:454	each ingredient	440:454	An experiment was conducted to quantify nutrient and fiber fractions of feed ingredients and to determine in vitro apparent ileal digestibility (IVAID) and in vitro apparent total tract digestibility (IVATTD) of DM and OM in each ingredient.
29385488	2	113	dep	ingredients	461:471	arg1	SBM					560:562	SBM	560:562	SBM	560:562	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	distillers					579:588	distillers	579:588	distillers dried grains with solubles (DDGS)	579:622	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	corn					533:536	corn	533:536	corn	533:536	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	expellers					647:655	copra expellers	641:655	copra expellers	641:655	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	SBP					675:677	SBP	675:677	SBP	675:677	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	pectin					711:716	pectin	711:716	pectin	711:716	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	wheat					539:543	wheat	539:543	wheat	539:543	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	cellulose					691:699	synthetic cellulose	681:699	synthetic cellulose (SF)	681:704	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	SF					702:703	SF	702:703	SF	702:703	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	meal					573:576	canola meal	566:576	canola meal	566:576	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	pulp					669:672	sugar beet pulp	658:672	sugar beet pulp (SBP)	658:678	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	meal					554:557	soybean meal	546:557	soybean meal (SBM)	546:563	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	113	dep	ingredients	461:471	arg1	meal					635:638	corn germ meal	625:638	corn germ meal	625:638	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	7	114	theme	components	1333:1342	arg1	GE					1314:1315	the calculated GE	1299:1315	the calculated GE of the analyzed components	1299:1342	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	7	114	theme	components	1333:1342	arg1	GE					1361:1362	the analyzed GE	1348:1362	the analyzed GE of the ingredients	1348:1381	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	9	115	theme	total	1592:1596	arg1	TDF					1613:1615	TDF	1613:1615	TDF	1613:1615	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	9	115	theme	total	1592:1596	arg1	fiber					1606:1610	total dietary fiber	1592:1610	total dietary fiber (TDF)	1592:1616	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	5	116	theme	energy-contributing	1028:1046	arg1	components					1048:1057	all energy-contributing components	1024:1057	all energy-contributing components	1024:1057	The analyzed GE was compared with values for GE calculated from all energy-contributing components.
29385488	13	117	theme	energy-contributing	2429:2447	arg1	components					2449:2458	energy-contributing components	2429:2458	energy-contributing components	2429:2458	In conclusion, the calculated GE of some feed ingredients was in agreement with the analyzed GE, which gives confidence that energy-contributing components were accounted for, but for DDGS and SBP, it was not possible to account for all analyzed GE.
29385488	9	118	theme	fiber	1606:1610	arg1	concentration					1541:1553	The concentration	1537:1553	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF)	1537:1616	The concentration of insoluble dietary fiber (IDF) and total dietary fiber (TDF) was negatively correlated (P < 0.05) with IVAID and IVATTD of DM and OM.
29385488	12	119	theme	TDF	2195:2197	arg1	concentration					2178:2190	the concentration	2174:2190	the concentration of TDF in feed ingredients	2174:2217	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	12	119	theme	TDF	2195:2197	arg1	predictor					2231:2239	a better predictor	2222:2239	a better predictor of the digestibility of DM and OM than values for NDF and ADF	2222:2301	The stronger correlations between IDF, TDF, and insoluble non-starch polysaccharides and IVAID and IVATTD of DM and OM than between ADF and NDF and IVAID and IVATTD of DM and OM indicate that the concentration of TDF in feed ingredients is a better predictor of the digestibility of DM and OM than values for NDF and ADF.
29385488	14	120	theme	ingredients	2630:2640	arg1	characteristics					2606:2620	the physical characteristics	2593:2620	the physical characteristics of feed ingredients	2593:2640	Concentrations of IDF and TDF, but not the physical characteristics of feed ingredients, may be used to estimate IVAID and IVATTD of DM and OM in feed ingredients.
29385488	7	121	theme	GE	1314:1315	arg1	sum					1292:1294	the sum	1288:1294	the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients	1288:1381	The difference between the sum of the calculated GE of the analyzed components and the analyzed GE of the ingredients ranged from -2.25 MJ/kg in DDGS to 1.74 MJ/kg in pectin.
29385488	2	122	theme	synthetic	681:689	arg1	SF					702:703	SF	702:703	SF	702:703	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	122	theme	synthetic	681:689	arg1	cellulose					691:699	synthetic cellulose	681:699	synthetic cellulose (SF)	681:704	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
29385488	2	122	theme	synthetic	681:689	arg1	ingredients					461:471	Ten ingredients	457:471	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.	457:717	Ten ingredients that vary in fiber concentration and composition were used: corn, wheat, soybean meal (SBM), canola meal, distillers dried grains with solubles (DDGS), corn germ meal, copra expellers, sugar beet pulp (SBP), synthetic cellulose (SF), and pectin.
30290860	8	0	theme	proteins	1141:1148	arg1	weights					1130:1136	The molecular weights	1116:1136	The molecular weights of proteins	1116:1148	The molecular weights of proteins ranged from approximately 30-50kDa and the majority of isoelectric points ranged from 6 to 8.
30290860	9	1	theme	predominant	1287:1297	arg1	bacteria					1299:1306	the predominant bacteria	1283:1306	the predominant bacteria	1283:1306	High-throughput sequencing showed that the predominant bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake layers.
30290860	9	1	theme	predominant	1287:1297	arg1	Proteobacteria					1313:1326	Proteobacteria	1313:1326	Proteobacteria	1313:1326	High-throughput sequencing showed that the predominant bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake layers.
30290860	4	2	theme	membrane	703:710	arg1	water					717:721	the membrane tank water	699:721	the membrane tank water	699:721	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	10	3	theme	strong	1526:1531	arg1	layer					1458:1462	the cake layer	1449:1462	the cake layer	1449:1462	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	10	3	theme	strong	1526:1531	arg1	resistance					1543:1552	the strong oxidative resistance	1522:1552	the strong oxidative resistance of its cell wall	1522:1569	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	1	4	theme	ultrafiltration	166:180	arg1	fouling					191:197	ultrafiltration membrane fouling	166:197	ultrafiltration membrane fouling	166:197	Pre-oxidation is widely used to reduce ultrafiltration membrane fouling.
30290860	2	5	from	pre-oxidation	326:338	arg1	treatment					358:366	drinking water treatment	343:366	drinking water treatment	343:366	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	10	6	theme	oxidative	1533:1541	arg1	layer					1458:1462	the cake layer	1449:1462	the cake layer	1449:1462	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	10	6	theme	oxidative	1533:1541	arg1	resistance					1543:1552	the strong oxidative resistance	1522:1552	the strong oxidative resistance of its cell wall	1522:1569	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	0	7	from	effects	4:10	arg1	membrane					66:73	ultrafiltration membrane	50:73	ultrafiltration membrane	50:73	The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane biofouling alleviation in drinking water treatment.
30290860	10	8	theme	cake	1453:1456	arg1	layer					1458:1462	the cake layer	1449:1462	the cake layer	1449:1462	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	10	8	theme	cake	1453:1456	arg1	resistance					1543:1552	the strong oxidative resistance	1522:1552	the strong oxidative resistance of its cell wall	1522:1569	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	5	9	attach	released	816:823	arg1	microbes					834:841	the microbes	830:841	the microbes	830:841	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	5	9	attach	released	816:823	arg2	EPS					812:814	EPS	812:814	EPS released from the microbes	812:841	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	1	10	theme	membrane	182:189	arg1	fouling					191:197	ultrafiltration membrane fouling	166:197	ultrafiltration membrane fouling	166:197	Pre-oxidation is widely used to reduce ultrafiltration membrane fouling.
30290860	2	11	from	variation	213:221	arg1	composition					230:240	the composition	226:240	the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment	226:366	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	4	12	theme	reactor	523:529	arg1	60d					543:545	60d	543:545	60d	543:545	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	4	12	theme	reactor	523:529	arg1	experiment					531:540	A long-term reactor experiment	511:540	A long-term reactor experiment (60d)	511:546	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	10	13	theme	relative	1398:1405	arg1	abundance					1407:1415	the relative abundance	1394:1415	the relative abundance of Planctomycetes	1394:1433	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	10	13	theme	relative	1398:1405	arg1	higher					1439:1444	higher	1439:1444	higher	1439:1444	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	11	14	theme	fundamental	1606:1616	arg1	mechanism					1628:1636	the fundamental molecular mechanism	1602:1636	the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment	1602:1739	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	2	15	theme	water	352:356	arg1	treatment					358:366	drinking water treatment	343:366	drinking water treatment	343:366	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	11	16	theme	bio-fouling	1689:1699	arg1	alleviation					1701:1711	ultrafiltration membrane bio-fouling alleviation	1664:1711	ultrafiltration membrane bio-fouling alleviation in drinking water treatment	1664:1739	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	3	17	used	used	443:446	arg2	H2O2					433:436	H2O2	433:436	H2O2	433:436	In this study, hydrogen peroxide (H2O2) was used in a coagulation-ultrafiltration process with Al2(SO4)3·18H2O.
30290860	3	17	used	used	443:446	arg2	peroxide					423:430	hydrogen peroxide	414:430	hydrogen peroxide (H2O2)	414:437	In this study, hydrogen peroxide (H2O2) was used in a coagulation-ultrafiltration process with Al2(SO4)3·18H2O.
30290860	10	18	theme	wall	1566:1569	arg1	layer					1458:1462	the cake layer	1449:1462	the cake layer	1449:1462	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	10	18	theme	wall	1566:1569	arg1	resistance					1543:1552	the strong oxidative resistance	1522:1552	the strong oxidative resistance of its cell wall	1522:1569	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	4	19	theme	water	717:721	arg1	measurements					683:694	flow cytometry measurements	668:694	flow cytometry measurements of the membrane tank water	668:721	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	7	20	theme	little	976:981	arg1	difference					983:992	little difference	976:992	little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2	976:1113	2D-electrophoresis showed little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2.
30290860	0	21	dep	water	110:114	arg1	treatment					116:124	treatment	116:124	water treatment	110:124	The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane biofouling alleviation in drinking water treatment.
30290860	5	22	theme	H2O2	872:875	arg1	treatment					877:885	H2O2 treatment	872:885	H2O2 treatment	872:885	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	5	23	theme	formed	748:753	arg1	layer					760:764	the formed cake layer	744:764	the formed cake layer	744:764	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	11	24	theme	ultrafiltration	1664:1678	arg1	alleviation					1701:1711	ultrafiltration membrane bio-fouling alleviation	1664:1711	ultrafiltration membrane bio-fouling alleviation in drinking water treatment	1664:1739	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	8	25	theme	points	1217:1222	arg1	majority					1193:1200	the majority	1189:1200	the majority of isoelectric points	1189:1222	The molecular weights of proteins ranged from approximately 30-50kDa and the majority of isoelectric points ranged from 6 to 8.
30290860	10	26	with	layer	1458:1462	arg1	pre-oxidation					1474:1486	H2O2 pre-oxidation	1469:1486	H2O2 pre-oxidation	1469:1486	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	3	27	theme	coagulation-ultrafiltration	453:479	arg1	process					481:487	a coagulation-ultrafiltration process	451:487	a coagulation-ultrafiltration process with Al2(SO4)3·18H2O	451:508	In this study, hydrogen peroxide (H2O2) was used in a coagulation-ultrafiltration process with Al2(SO4)3·18H2O.
30290860	3	28	theme	hydrogen	414:421	arg1	H2O2					433:436	H2O2	433:436	H2O2	433:436	In this study, hydrogen peroxide (H2O2) was used in a coagulation-ultrafiltration process with Al2(SO4)3·18H2O.
30290860	3	28	theme	hydrogen	414:421	arg1	peroxide					423:430	hydrogen peroxide	414:430	hydrogen peroxide (H2O2)	414:437	In this study, hydrogen peroxide (H2O2) was used in a coagulation-ultrafiltration process with Al2(SO4)3·18H2O.
30290860	11	29	theme	membrane	1680:1687	arg1	alleviation					1701:1711	ultrafiltration membrane bio-fouling alleviation	1664:1711	ultrafiltration membrane bio-fouling alleviation in drinking water treatment	1664:1739	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	10	30	theme	H2O2	1469:1472	arg1	pre-oxidation					1474:1486	H2O2 pre-oxidation	1469:1486	H2O2 pre-oxidation	1469:1486	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	1	31	used	used	151:154	arg2	Pre-oxidation					127:139	Pre-oxidation	127:139	Pre-oxidation	127:139	Pre-oxidation is widely used to reduce ultrafiltration membrane fouling.
30290860	4	32	theme	cytometry	673:681	arg1	measurements					683:694	flow cytometry measurements	668:694	flow cytometry measurements of the membrane tank water	668:721	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	7	33	from	difference	983:992	arg1	composition					1028:1038	the composition	1024:1038	the composition of proteins in the cake layer	1024:1068	2D-electrophoresis showed little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2.
30290860	9	34	from	Verrucomicrobia	1348:1362	arg1	layers					1377:1382	both cake layers	1367:1382	both cake layers	1367:1382	High-throughput sequencing showed that the predominant bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake layers.
30290860	7	35	theme	cake	1059:1062	arg1	layer					1064:1068	the cake layer	1055:1068	the cake layer	1055:1068	2D-electrophoresis showed little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2.
30290860	2	36	theme	drinking	343:350	arg1	water					352:356	drinking water	343:356	drinking water treatment	343:366	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	4	37	theme	flow	668:671	arg1	measurements					683:694	flow cytometry measurements	668:694	flow cytometry measurements of the membrane tank water	668:721	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	0	38	theme	hydrogen	15:22	arg1	peroxide					24:31	hydrogen peroxide	15:31	hydrogen peroxide pre-oxidation	15:45	The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane biofouling alleviation in drinking water treatment.
30290860	10	39	theme	Planctomycetes	1420:1433	arg1	abundance					1407:1415	the relative abundance	1394:1415	the relative abundance of Planctomycetes	1394:1433	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	10	39	theme	Planctomycetes	1420:1433	arg1	higher					1439:1444	higher	1439:1444	higher	1439:1444	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	3	40	with	process	481:487	arg1	3·18H2O					502:508	Al2(SO4)3·18H2O	494:508	Al2(SO4)3·18H2O	494:508	In this study, hydrogen peroxide (H2O2) was used in a coagulation-ultrafiltration process with Al2(SO4)3·18H2O.
30290860	3	41	theme	Al2	494:496	arg1	3·18H2O					502:508	Al2(SO4)3·18H2O	494:508	Al2(SO4)3·18H2O	494:508	In this study, hydrogen peroxide (H2O2) was used in a coagulation-ultrafiltration process with Al2(SO4)3·18H2O.
30290860	8	42	dep	8	1241:1241	arg1	to					1238:1239	to	1238:1239	to	1238:1239	The molecular weights of proteins ranged from approximately 30-50kDa and the majority of isoelectric points ranged from 6 to 8.
30290860	4	43	theme	membrane	585:592	arg1	fouling					594:600	membrane fouling	585:600	membrane fouling	585:600	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	11	44	theme	water	1725:1729	arg1	treatment					1731:1739	water treatment	1725:1739	water treatment	1725:1739	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	4	45	theme	microbial	635:643	arg1	growth					645:650	microbial growth	635:650	microbial growth	635:650	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	0	46	theme	pre-oxidation	33:45	arg1	effects					4:10	The effects	0:10	The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane	0:73	The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane biofouling alleviation in drinking water treatment.
30290860	2	47	theme	communities	255:265	arg1	composition					230:240	the composition	226:240	the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment	226:366	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	11	48	from	mechanism	1628:1636	arg1	pre-oxidation					1646:1658	H2O2 pre-oxidation	1641:1658	H2O2 pre-oxidation	1641:1658	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	0	49	theme	peroxide	24:31	arg1	pre-oxidation					33:45	hydrogen peroxide pre-oxidation	15:45	hydrogen peroxide pre-oxidation	15:45	The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane biofouling alleviation in drinking water treatment.
30290860	9	50	theme	cake	1372:1375	arg1	layers					1377:1382	both cake layers	1367:1382	both cake layers	1367:1382	High-throughput sequencing showed that the predominant bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake layers.
30290860	5	51	theme	corresponding	788:800	arg1	levels					802:807	the corresponding levels	784:807	the corresponding levels of EPS released from the microbes	784:841	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	5	51	theme	corresponding	788:800	arg1	lower					848:852	lower	848:852	lower	848:852	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	11	52	theme	H2O2	1641:1644	arg1	pre-oxidation					1646:1658	H2O2 pre-oxidation	1641:1658	H2O2 pre-oxidation	1641:1658	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	2	53	theme	microbial	245:253	arg1	communities					255:265	microbial communities	245:265	microbial communities	245:265	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	10	54	theme	cell	1561:1564	arg1	wall					1566:1569	its cell wall	1557:1569	its cell wall	1557:1569	However, the relative abundance of Planctomycetes was higher in the cake layer with H2O2 pre-oxidation, which was likely probably due to the strong oxidative resistance of its cell wall.
30290860	0	55	theme	ultrafiltration	50:64	arg1	membrane					66:73	ultrafiltration membrane	50:73	ultrafiltration membrane	50:73	The effects of hydrogen peroxide pre-oxidation on ultrafiltration membrane biofouling alleviation in drinking water treatment.
30290860	7	56	theme	proteins	1043:1050	arg1	composition					1028:1038	the composition	1024:1038	the composition of proteins in the cake layer	1024:1068	2D-electrophoresis showed little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2.
30290860	8	57	theme	molecular	1120:1128	arg1	weights					1130:1136	The molecular weights	1116:1136	The molecular weights of proteins	1116:1148	The molecular weights of proteins ranged from approximately 30-50kDa and the majority of isoelectric points ranged from 6 to 8.
30290860	2	58	theme	little	381:386	arg1	attention					388:396	little attention	381:396	little attention	381:396	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	5	59	theme	Further	724:730	arg1	analysis					732:739	Further analysis	724:739	Further analysis of the formed cake layer	724:764	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	9	60	theme	High-throughput	1244:1258	arg1	sequencing					1260:1269	High-throughput sequencing	1244:1269	High-throughput sequencing	1244:1269	High-throughput sequencing showed that the predominant bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake layers.
30290860	4	61	theme	tank	712:715	arg1	water					717:721	the membrane tank water	699:721	the membrane tank water	699:721	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	2	62	theme	substances	295:304	arg1	composition					230:240	the composition	226:240	the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment	226:366	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	9	63	from	Proteobacteria	1313:1326	arg1	layers					1377:1382	both cake layers	1367:1382	both cake layers	1367:1382	High-throughput sequencing showed that the predominant bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake layers.
30290860	7	64	from	composition	1028:1038	arg1	layer					1064:1068	the cake layer	1055:1068	the cake layer	1055:1068	2D-electrophoresis showed little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2.
30290860	2	65	theme	polymeric	285:293	arg1	EPSs					307:310	EPSs	307:310	EPSs	307:310	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	2	65	theme	polymeric	285:293	arg1	substances					295:304	extracellular polymeric substances	271:304	extracellular polymeric substances (EPSs)	271:311	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	11	66	theme	molecular	1618:1626	arg1	mechanism					1628:1636	the fundamental molecular mechanism	1602:1636	the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment	1602:1739	Overall, our findings clarify the fundamental molecular mechanism in H2O2 pre-oxidation for ultrafiltration membrane bio-fouling alleviation in drinking water treatment.
30290860	7	67	dep	difference	983:992	arg1	p>0.05					995:1000	p>0.05	995:1000	p>0.05	995:1000	2D-electrophoresis showed little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2.
30290860	7	67	dep	difference	983:992	arg1	t-test					1013:1018	Student's t-test	1003:1018	Student's t-test	1003:1018	2D-electrophoresis showed little difference (p>0.05, Student's t-test) in the composition of proteins in the cake layer between the treatments with and without H2O2.
30290860	8	68	theme	isoelectric	1205:1215	arg1	points					1217:1222	isoelectric points	1205:1222	isoelectric points	1205:1222	The molecular weights of proteins ranged from approximately 30-50kDa and the majority of isoelectric points ranged from 6 to 8.
30290860	5	69	theme	cake	755:758	arg1	layer					760:764	the formed cake layer	744:764	the formed cake layer	744:764	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	2	70	theme	extracellular	271:283	arg1	EPSs					307:310	EPSs	307:310	EPSs	307:310	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	2	70	theme	extracellular	271:283	arg1	substances					295:304	extracellular polymeric substances	271:304	extracellular polymeric substances (EPSs)	271:311	However, the variation in the composition of microbial communities and extracellular polymeric substances (EPSs) accompanying pre-oxidation in drinking water treatment has received little attention.
30290860	4	71	theme	growth	645:650	arg1	inhibition					621:630	its inhibition	617:630	its inhibition of microbial growth	617:650	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	5	72	theme	layer	760:764	arg1	analysis					732:739	Further analysis	724:739	Further analysis of the formed cake layer	724:764	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	4	73	theme	long-term	513:521	arg1	60d					543:545	60d	543:545	60d	543:545	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	4	73	theme	long-term	513:521	arg1	experiment					531:540	A long-term reactor experiment	511:540	A long-term reactor experiment (60d)	511:546	A long-term reactor experiment (60d) showed that pre-oxidation alleviated membrane fouling, mainly due to its inhibition of microbial growth, as observed by flow cytometry measurements of the membrane tank water.
30290860	5	74	theme	EPS	812:814	arg1	levels					802:807	the corresponding levels	784:807	the corresponding levels of EPS released from the microbes	784:841	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	5	74	theme	EPS	812:814	arg1	lower					848:852	lower	848:852	lower	848:852	Further analysis of the formed cake layer demonstrated that the corresponding levels of EPS released from the microbes were lower with than without H2O2 treatment.
30290860	9	75	from	Bacteroidetes	1329:1341	arg1	layers					1377:1382	both cake layers	1367:1382	both cake layers	1367:1382	High-throughput sequencing showed that the predominant bacteria were Proteobacteria, Bacteroidetes, and Verrucomicrobia in both cake layers.
30784742	5	0	theme	full-scale	1164:1173	arg1	digestates					1181:1190	different full-scale plant digestates	1154:1190	different full-scale plant digestates	1154:1190	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	6	1	theme	linear	1195:1200	arg1	regression					1202:1211	A linear regression	1193:1211	A linear regression with an R2 of 0.9863	1193:1232	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	4	2	theme	thermophilic	858:869	arg1	environment					871:881	a thermophilic environment	856:881	a thermophilic environment	856:881	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	0	3	theme	organic	92:98	arg1	carbon					100:105	dissolved organic carbon	82:105	dissolved organic carbon	82:105	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	6	4	theme	0.9863	1227:1232	arg1	R2					1221:1222	an R2	1218:1222	an R2 of 0.9863	1218:1232	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	4	5	theme	laboratory	675:684	arg1	KDOCs					707:711	log KDOCs	703:711	log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure	703:840	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	4	5	theme	laboratory	675:684	arg1	samples					686:692	the laboratory samples	671:692	the laboratory samples	671:692	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	2	6	theme	DOC	502:504	arg1	solutions					506:514	four DOC solutions	497:514	four DOC solutions from two laboratories and two full-scale anaerobic digestion plants	497:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	5	7	theme	different	1154:1162	arg1	digestates					1181:1190	different full-scale plant digestates	1154:1190	different full-scale plant digestates	1154:1190	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	2	8	from	laboratories	525:536	arg1	solutions					506:514	four DOC solutions	497:514	four DOC solutions from two laboratories and two full-scale anaerobic digestion plants	497:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	2	8	from	laboratories	525:536	arg1	presence					485:492	the presence	481:492	the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants	481:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	1	9	theme	present	350:356	arg1	DOC					345:347	DOC	345:347	DOC	345:347	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	9	theme	present	350:356	arg1	carbon					337:342	dissolved organic carbon	319:342	dissolved organic carbon (DOC) present in wastewater	319:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	2	10	theme	digestion	567:575	arg1	plants					577:582	two full-scale anaerobic digestion plants	542:582	two full-scale anaerobic digestion plants	542:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	4	11	theme	mesophilic	941:950	arg1	conditions					952:961	mesophilic conditions	941:961	mesophilic conditions	941:961	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	1	12	theme	polybrominated	277:290	arg1	PBDEs					309:313	PBDEs	309:313	PBDEs	309:313	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	12	theme	polybrominated	277:290	arg1	ethers					301:306	polybrominated diphenyl ethers	277:306	polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater	277:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	5	13	theme	highest	1071:1077	arg1	KDOCs					1083:1087	the highest log KDOCs	1067:1087	the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether	1067:1130	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	5	13	theme	highest	1071:1077	arg1	6.71					1137:1140	6.71	1137:1140	6.71	1137:1140	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	5	14	from	6.71	1137:1140	arg1	digestates					1181:1190	different full-scale plant digestates	1154:1190	different full-scale plant digestates	1154:1190	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	4	15	theme	greater	921:927	arg1	extent					929:934	a greater extent	919:934	a greater extent than mesophilic conditions	919:961	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	5	16	theme	log	1079:1081	arg1	KDOCs					1083:1087	the highest log KDOCs	1067:1087	the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether	1067:1130	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	5	16	theme	log	1079:1081	arg1	6.71					1137:1140	6.71	1137:1140	6.71	1137:1140	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	2	17	theme	PBDEs	458:462	arg1	concentrations					428:441	the concentrations	424:441	the concentrations of four common PBDEs	424:462	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	6	18	theme	different	1515:1523	arg1	systems					1531:1537	different water systems	1515:1537	different water systems	1515:1537	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	6	19	dep	used	1238:1241	arg1	includes					1353:1360	includes	1353:1360	includes proteins, polysaccharides and lipids	1353:1397	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	6	19	dep	used	1238:1241	arg1	takes					1410:1414	takes	1410:1414	takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems	1410:1537	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	4	20	theme	PBDEs	910:914	arg1	solubility					896:905	the solubility	892:905	the solubility of PBDEs	892:914	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	2	21	theme	current	380:386	arg1	study					388:392	the current study	376:392	the current study	376:392	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	1	22	from	wastewater	361:370	arg1	present					350:356	present	350:356	present	350:356	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	4	23	theme	cultivate	822:830	arg1	procedure					832:840	the cultivate procedure	818:840	the cultivate procedure	818:840	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	2	24	from	plants	577:582	arg1	solutions					506:514	four DOC solutions	497:514	four DOC solutions from two laboratories and two full-scale anaerobic digestion plants	497:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	2	24	from	plants	577:582	arg1	presence					485:492	the presence	481:492	the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants	481:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	0	25	theme	Distribution	0:11	arg1	characteristics					13:27	Distribution characteristics	0:27	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic	0:120	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	1	26	theme	diphenyl	292:299	arg1	PBDEs					309:313	PBDEs	309:313	PBDEs	309:313	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	26	theme	diphenyl	292:299	arg1	ethers					301:306	polybrominated diphenyl ethers	277:306	polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater	277:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	27	from	ethers	301:306	arg1	DOC					345:347	DOC	345:347	DOC	345:347	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	27	from	ethers	301:306	arg1	carbon					337:342	dissolved organic carbon	319:342	dissolved organic carbon (DOC) present in wastewater	319:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	6	28	theme	water	1525:1529	arg1	systems					1531:1537	different water systems	1515:1537	different water systems	1515:1537	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	6	29	theme	atoms	1454:1458	arg1	positions					1433:1441	the positions	1429:1441	the positions of bromine atoms	1429:1458	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	5	30	theme	cultivating	1042:1052	arg1	temperature					1054:1064	the same cultivating temperature	1033:1064	the same cultivating temperature	1033:1064	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	0	31	theme	poly-brominated	32:46	arg1	ethers					57:62	poly-brominated diphenyl ethers	32:62	poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic	32:120	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	1	32	theme	ethers	301:306	arg1	coefficients					230:241	the partition coefficients	216:241	the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater	216:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	6	33	theme	potential	1279:1287	arg1	relationship					1289:1300	the potential relationship	1275:1300	the potential relationship between log KDOC and the composition of DOC	1275:1344	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	5	34	theme	PBDEs	1018:1022	arg1	solubility					1004:1013	the solubility	1000:1013	the solubility of PBDEs	1000:1022	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	6	35	theme	bromine	1446:1452	arg1	atoms					1454:1458	bromine atoms	1446:1458	bromine atoms	1446:1458	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	2	36	theme	equilibration	409:421	arg1	72 h					401:404	72 h	401:404	72 h of equilibration	401:421	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	5	37	theme	same	1037:1040	arg1	temperature					1054:1064	the same cultivating temperature	1033:1064	the same cultivating temperature	1033:1064	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	2	38	theme	common	451:456	arg1	PBDEs					458:462	four common PBDEs	446:462	four common PBDEs	446:462	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	1	39	theme	partition	220:228	arg1	coefficients					230:241	the partition coefficients	216:241	the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater	216:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	0	40	theme	ethers	57:62	arg1	characteristics					13:27	Distribution characteristics	0:27	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic	0:120	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	0	41	theme	conditions	154:163	arg1	Effects					133:139	Effects	133:139	Effects of digestion conditions	133:163	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	3	42	theme	unit	638:641	arg1	conversion					643:652	unit conversion	638:652	unit conversion	638:652	Sixteen log KDOCs were determined by calculation and unit conversion.
30784742	4	43	theme	5.46 at	771:777	arg1	temperatures					798:809	5.46 at different reaction temperatures	771:809	5.46 at different reaction temperatures	771:809	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	6	44	used	used	1238:1241	arg2	regression					1202:1211	A linear regression	1193:1211	A linear regression with an R2 of 0.9863	1193:1232	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	0	45	theme	diphenyl	48:55	arg1	ethers					57:62	poly-brominated diphenyl ethers	32:62	poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic	32:120	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	0	46	theme	digestion	144:152	arg1	conditions					154:163	digestion conditions	144:163	digestion conditions	144:163	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	1	47	from	present	350:356	arg1	wastewater					361:370	wastewater	361:370	wastewater	361:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	48	from	coefficients	230:241	arg1	DOC					345:347	DOC	345:347	DOC	345:347	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	48	from	coefficients	230:241	arg1	carbon					337:342	dissolved organic carbon	319:342	dissolved organic carbon (DOC) present in wastewater	319:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	5	49	theme	5,6'-hexabromodiphenyl	1103:1124	arg1	2,2					1093:1095	2,2'	1093:1096	2,2'	1093:1096	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	5	49	theme	5,6'-hexabromodiphenyl	1103:1124	arg1	ether					1126:1130	5,6'-hexabromodiphenyl ether	1103:1130	5,6'-hexabromodiphenyl ether	1103:1130	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	1	50	from	carbon	337:342	arg1	coefficients					230:241	the partition coefficients	216:241	the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater	216:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	2	51	theme	anaerobic	557:565	arg1	plants					577:582	two full-scale anaerobic digestion plants	542:582	two full-scale anaerobic digestion plants	542:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	4	52	theme	reaction	789:796	arg1	temperatures					798:809	5.46 at different reaction temperatures	771:809	5.46 at different reaction temperatures	771:809	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	6	53	theme	PBDEs	1506:1510	arg1	values					1496:1501	the log KDOC values	1483:1501	the log KDOC values of PBDEs	1483:1510	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	2	54	theme	solutions	506:514	arg1	presence					485:492	the presence	481:492	the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants	481:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	1	55	theme	dissolved	319:327	arg1	DOC					345:347	DOC	345:347	DOC	345:347	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	55	theme	dissolved	319:327	arg1	carbon					337:342	dissolved organic carbon	319:342	dissolved organic carbon (DOC) present in wastewater	319:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	2	56	theme	full-scale	546:555	arg1	plants					577:582	two full-scale anaerobic digestion plants	542:582	two full-scale anaerobic digestion plants	542:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	4	57	theme	different	779:787	arg1	temperatures					798:809	5.46 at different reaction temperatures	771:809	5.46 at different reaction temperatures	771:809	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	1	58	theme	organic	329:335	arg1	DOC					345:347	DOC	345:347	DOC	345:347	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	58	theme	organic	329:335	arg1	carbon					337:342	dissolved organic carbon	319:342	dissolved organic carbon (DOC) present in wastewater	319:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	2	59	from	presence	485:492	arg1	laboratories					525:536	two laboratories	521:536	two laboratories	521:536	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	2	59	from	presence	485:492	arg1	plants					577:582	two full-scale anaerobic digestion plants	542:582	two full-scale anaerobic digestion plants	542:582	In the current study, after 72 h of equilibration, the concentrations of four common PBDEs were measured in the presence of four DOC solutions from two laboratories and two full-scale anaerobic digestion plants.
30784742	1	60	dep	coefficients	230:241	arg1	expressed					244:252	expressed	244:252	expressed as log KDOC values	244:271	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	4	61	theme	log	703:705	arg1	KDOCs					707:711	log KDOCs	703:711	log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure	703:840	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	5	62	theme	plant	1175:1179	arg1	digestates					1181:1190	different full-scale plant digestates	1154:1190	different full-scale plant digestates	1154:1190	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	0	63	from	anaerobic	112:120	arg1	carbon					100:105	dissolved organic carbon	82:105	dissolved organic carbon	82:105	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	0	63	from	anaerobic	112:120	arg1	water					72:76	water	72:76	water	72:76	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	4	64	theme	5,5'-hexabromodiphenyl	727:748	arg1	ether					750:754	5,5'-hexabromodiphenyl ether	727:754	5,5'-hexabromodiphenyl ether being 6.38	727:765	The results for the laboratory samples, such as log KDOCs for 2,2',4,4',5,5'-hexabromodiphenyl ether being 6.38 and 5.46 at different reaction temperatures during the cultivate procedure, suggest that a thermophilic environment promotes the solubility of PBDEs to a greater extent than mesophilic conditions.
30784742	6	65	theme	KDOC	1491:1494	arg1	values					1496:1501	the log KDOC values	1483:1501	the log KDOC values of PBDEs	1483:1510	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	6	66	theme	log	1310:1312	arg1	KDOC					1314:1317	log KDOC	1310:1317	log KDOC	1310:1317	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	0	67	theme	dissolved	82:90	arg1	carbon					100:105	dissolved organic carbon	82:105	dissolved organic carbon	82:105	Distribution characteristics of poly-brominated diphenyl ethers between water and dissolved organic carbon from anaerobic digestate: Effects of digestion conditions.
30784742	3	68	theme	log	593:595	arg1	KDOCs					597:601	Sixteen log KDOCs	585:601	Sixteen log KDOCs	585:601	Sixteen log KDOCs were determined by calculation and unit conversion.
30784742	6	69	theme	log	1487:1489	arg1	values					1496:1501	the log KDOC values	1483:1501	the log KDOC values of PBDEs	1483:1510	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	6	70	theme	DOC	1342:1344	arg1	KDOC					1314:1317	log KDOC	1310:1317	log KDOC	1310:1317	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	6	70	theme	DOC	1342:1344	arg1	composition					1327:1337	the composition	1323:1337	the composition of DOC	1323:1344	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	1	71	theme	log	257:259	arg1	values					266:271	log KDOC values	257:271	log KDOC values	257:271	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	5	72	theme	DOC	964:966	arg1	composition					968:978	DOC composition	964:978	DOC composition	964:978	DOC composition directly influences the solubility of PBDEs, even at the same cultivating temperature: the highest log KDOCs for 2,2',4,4',5,6'-hexabromodiphenyl ether were 6.71 and 6.33 in different full-scale plant digestates.
30784742	1	73	attach	present	350:356	arg2	carbon					337:342	dissolved organic carbon	319:342	dissolved organic carbon (DOC) present in wastewater	319:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	73	attach	present	350:356	arg1	wastewater					361:370	wastewater	361:370	wastewater	361:370	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	1	73	attach	present	350:356	arg2	DOC					345:347	DOC	345:347	DOC	345:347	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30784742	6	74	with	regression	1202:1211	arg1	R2					1221:1222	an R2	1218:1222	an R2 of 0.9863	1218:1232	A linear regression with an R2 of 0.9863 was used to construct a model describing the potential relationship between log KDOC and the composition of DOC, which includes proteins, polysaccharides and lipids, and which takes into account the positions of bromine atoms, for use in predicting the log KDOC values of PBDEs in different water systems.
30784742	1	75	theme	KDOC	261:264	arg1	values					266:271	log KDOC values	257:271	log KDOC values	257:271	It is becoming increasingly urgent to investigate the partition coefficients (expressed as log KDOC values) of polybrominated diphenyl ethers (PBDEs) in dissolved organic carbon (DOC) present in wastewater.
30291258	0	0	theme	cytokines	97:105	arg1	composition					52:62	gut microbiota composition	37:62	gut microbiota composition	37:62	Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice.
30291258	0	0	theme	cytokines	97:105	arg1	expression					72:81	the expression	68:81	the expression of intestinal cytokines in Peyer's patches of mice	68:132	Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice.
30291258	1	1	theme	homeostatic	343:353	arg1	properties					355:364	several distinctive homeostatic properties	323:364	several distinctive homeostatic properties	323:364	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	1	theme	homeostatic	343:353	arg1	control					375:381	control	375:381	control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation	375:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	4	2	theme	chow	847:850	arg1	diet					859:862	a normal chow pellet diet	838:862	a normal chow pellet diet	838:862	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	5	3	theme	sub-chronic	1168:1178	arg1	treatment					1184:1192	sub-chronic OEA treatment	1168:1192	sub-chronic OEA treatment	1168:1192	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	0	4	theme	intestinal	86:95	arg1	cytokines					97:105	intestinal cytokines	86:105	intestinal cytokines	86:105	Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice.
30291258	3	5	theme	modulatory	677:686	arg1	effect					688:693	an unexplored modulatory effect	663:693	an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response	663:752	Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response.
30291258	4	6	theme	normal	840:845	arg1	diet					859:862	a normal chow pellet diet	838:862	a normal chow pellet diet	838:862	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	5	7	theme	lean-like	1242:1250	arg1	"					1261:1261	a "lean-like phenotype"	1239:1261	a "lean-like phenotype"	1239:1261	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	5	8	theme	OEA	1180:1182	arg1	treatment					1184:1192	sub-chronic OEA treatment	1168:1192	sub-chronic OEA treatment	1168:1192	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	2	9	theme	cognitive	544:552	arg1	paradigms					554:562	several cognitive paradigms	536:562	several cognitive paradigms	536:562	When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis.
30291258	1	10	theme	fatty	453:457	arg1	oxidation					464:472	fatty acid oxidation	453:472	fatty acid oxidation	453:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	5	11	theme	phenotype	1252:1260	arg1	"					1261:1261	a "lean-like phenotype"	1239:1261	a "lean-like phenotype"	1239:1261	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	2	12	theme	several	536:542	arg1	paradigms					554:562	several cognitive paradigms	536:562	several cognitive paradigms	536:562	When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis.
30291258	3	13	theme	intestinal	709:718	arg1	microbiota					720:729	the intestinal microbiota	705:729	the intestinal microbiota	705:729	Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response.
30291258	4	14	theme	pellet	852:857	arg1	diet					859:862	a normal chow pellet diet	838:862	a normal chow pellet diet	838:862	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	1	15	theme	acid	459:462	arg1	oxidation					464:472	fatty acid oxidation	453:472	fatty acid oxidation	453:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	4	16	theme	Bacteroidetes	961:973	arg1	favour					951:956	favour	951:956	favour of Bacteroidetes (in particular Bacteroides genus)	951:1007	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	4	17	theme	Bacteroidetes	928:940	arg1	ratio					942:946	Bacteroidetes ratio	928:946	the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus)	913:1007	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	1	18	theme	oxidation	464:472	arg1	stimulation					424:434	stimulation	424:434	stimulation of lipolysis and fatty acid oxidation	424:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	18	theme	oxidation	464:472	arg1	appetite					386:393	appetite	386:393	appetite	386:393	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	4	19	theme	immune	1099:1104	arg1	cells					1106:1110	immune cells	1099:1110	immune cells isolated from Peyer's patches	1099:1140	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	2	20	theme	axis	642:645	arg1	hormone					617:623	a hormone	615:623	a hormone of the gut-brain axis	615:645	When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis.
30291258	5	21	theme	microbiota	1208:1217	arg1	composition					1219:1229	gut microbiota composition	1204:1229	gut microbiota composition towards a "lean-like phenotype"	1204:1261	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	4	22	from	favour	951:956	arg1	genus					1002:1006	particular Bacteroides genus	979:1006	particular Bacteroides genus	979:1006	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	4	23	dep	profile	895:901	arg1	decreasing					1013:1022	decreasing	1013:1022	decreasing Firmicutes (Lactobacillus)	1013:1049	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	4	23	dep	profile	895:901	arg1	shifting					904:911	shifting	904:911	shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus)	904:1007	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	0	24	theme	Oleoylethanolamide	0:17	arg1	treatment					19:27	Oleoylethanolamide treatment	0:27	Oleoylethanolamide treatment	0:27	Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice.
30291258	3	25	theme	immune	738:743	arg1	response					745:752	immune response	738:752	immune response	738:752	Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response.
30291258	4	26	theme	cytokines	1075:1083	arg1	expression					1085:1094	intestinal cytokines expression	1064:1094	intestinal cytokines expression by immune cells isolated from Peyer's patches	1064:1140	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	5	27	from	low	1339:1341	arg1	fat					1346:1348	fat	1346:1348	fat	1346:1348	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	0	28	theme	gut	37:39	arg1	composition					52:62	gut microbiota composition	37:62	gut microbiota composition	37:62	Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice.
30291258	1	29	theme	proximal	287:294	arg1	intestine					296:304	the proximal intestine	283:304	the proximal intestine	283:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	0	30	theme	mice	129:132	arg1	patches					118:124	Peyer's patches	110:124	Peyer's patches of mice	110:132	Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice.
30291258	1	31	with	endowed	310:316	arg1	properties					355:364	several distinctive homeostatic properties	323:364	several distinctive homeostatic properties	323:364	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	31	with	endowed	310:316	arg1	control					375:381	control	375:381	control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation	375:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	2	32	theme	gut-brain	632:640	arg1	axis					642:645	the gut-brain axis	628:645	the gut-brain axis	628:645	When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis.
30291258	4	33	theme	intestinal	1064:1073	arg1	expression					1085:1094	intestinal cytokines expression	1064:1094	intestinal cytokines expression by immune cells isolated from Peyer's patches	1064:1140	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	1	34	theme	endogenous	181:190	arg1	oleoylethanolamide					152:169	The lipid sensor oleoylethanolamide	135:169	The lipid sensor oleoylethanolamide (OEA)	135:175	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	34	theme	endogenous	181:190	arg1	agonist					206:212	an endogenous high-affinity agonist	178:212	an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine	178:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	4	35	from	genus	1002:1006	arg1	favour					951:956	favour	951:956	favour of Bacteroidetes (in particular Bacteroides genus)	951:1007	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	4	36	theme	microbiota	884:893	arg1	profile					895:901	the faecal microbiota profile	873:901	the faecal microbiota profile	873:901	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	1	37	theme	appetite	386:393	arg1	control					375:381	control	375:381	control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation	375:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	38	theme	high-affinity	192:204	arg1	oleoylethanolamide					152:169	The lipid sensor oleoylethanolamide	135:169	The lipid sensor oleoylethanolamide (OEA)	135:175	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	38	theme	high-affinity	192:204	arg1	agonist					206:212	an endogenous high-affinity agonist	178:212	an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine	178:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	5	39	theme	gut-specific	1278:1289	arg1	responses					1298:1306	gut-specific immune responses	1278:1306	gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content	1278:1384	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	4	40	dep	Firmicutes	917:926	arg1	ratio					942:946	Bacteroidetes ratio	928:946	the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus)	913:1007	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	5	41	theme	gut	1204:1206	arg1	composition					1219:1229	gut microbiota composition	1204:1229	gut microbiota composition towards a "lean-like phenotype"	1204:1261	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	4	42	theme	sub-chronic	795:805	arg1	administration					811:824	sub-chronic OEA administration	795:824	sub-chronic OEA administration to mice	795:832	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	0	43	theme	microbiota	41:50	arg1	composition					52:62	gut microbiota composition	37:62	gut microbiota composition	37:62	Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer's patches of mice.
30291258	3	44	from	effect	688:693	arg1	response					745:752	immune response	738:752	immune response	738:752	Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response.
30291258	3	44	from	effect	688:693	arg1	microbiota					720:729	the intestinal microbiota	705:729	the intestinal microbiota	705:729	Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response.
30291258	1	45	theme	anti-inflammatory	396:412	arg1	appetite					386:393	appetite	386:393	appetite	386:393	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	45	theme	anti-inflammatory	396:412	arg1	activity					414:421	anti-inflammatory activity	396:421	anti-inflammatory activity	396:421	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	5	46	from	high	1354:1357	arg1	content					1378:1384	polysaccharides content	1362:1384	polysaccharides content	1362:1384	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	5	47	theme	high	1354:1357	arg1	diet					1334:1337	a diet	1332:1337	a diet low in fat and high in polysaccharides content	1332:1384	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	4	48	theme	OEA	807:809	arg1	administration					811:824	sub-chronic OEA administration	795:824	sub-chronic OEA administration to mice	795:832	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	2	49	contain	has	510:512	arg1	OEA					506:508	OEA	506:508	OEA	506:508	When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis.
30291258	2	49	contain	has	510:512	arg2	effects					525:531	beneficial effects	514:531	beneficial effects	514:531	When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis.
30291258	1	50	theme	several	323:329	arg1	properties					355:364	several distinctive homeostatic properties	323:364	several distinctive homeostatic properties	323:364	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	50	theme	several	323:329	arg1	control					375:381	control	375:381	control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation	375:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	4	51	theme	faecal	877:882	arg1	profile					895:901	the faecal microbiota profile	873:901	the faecal microbiota profile	873:901	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	3	52	theme	unexplored	666:675	arg1	effect					688:693	an unexplored modulatory effect	663:693	an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response	663:752	Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response.
30291258	5	53	theme	polysaccharides	1362:1376	arg1	content					1378:1384	polysaccharides content	1362:1384	polysaccharides content	1362:1384	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	5	54	from	content	1378:1384	arg1	high					1354:1357	high	1354:1357	high	1354:1357	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	1	55	theme	peroxisome	217:226	arg1	receptor-α					251:260	peroxisome proliferator-activated receptor-α	217:260	peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine	217:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	55	theme	peroxisome	217:226	arg1	PPAR-α					263:268	PPAR-α	263:268	PPAR-α	263:268	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	5	56	theme	diet	1334:1337	arg1	effect					1322:1327	the effect	1318:1327	the effect of a diet low in fat and high in polysaccharides content	1318:1384	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	5	57	theme	immune	1291:1296	arg1	responses					1298:1306	gut-specific immune responses	1278:1306	gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content	1278:1384	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	1	58	theme	proliferator-activated	228:249	arg1	receptor-α					251:260	peroxisome proliferator-activated receptor-α	217:260	peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine	217:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	58	theme	proliferator-activated	228:249	arg1	PPAR-α					263:268	PPAR-α	263:268	PPAR-α	263:268	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	2	59	theme	beneficial	514:523	arg1	effects					525:531	beneficial effects	514:531	beneficial effects	514:531	When administered exogenously, OEA has beneficial effects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut-brain axis.
30291258	1	60	theme	lipolysis	439:447	arg1	stimulation					424:434	stimulation	424:434	stimulation of lipolysis and fatty acid oxidation	424:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	60	theme	lipolysis	439:447	arg1	appetite					386:393	appetite	386:393	appetite	386:393	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	5	61	theme	low	1339:1341	arg1	diet					1334:1337	a diet	1332:1337	a diet low in fat and high in polysaccharides content	1332:1384	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	1	62	theme	lipid	139:143	arg1	agonist					206:212	an endogenous high-affinity agonist	178:212	an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine	178:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	62	theme	lipid	139:143	arg1	OEA					172:174	OEA	172:174	OEA	172:174	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	62	theme	lipid	139:143	arg1	oleoylethanolamide					152:169	The lipid sensor oleoylethanolamide	135:169	The lipid sensor oleoylethanolamide (OEA)	135:175	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	62	theme	lipid	139:143	arg1	endowed					310:316	endowed	310:316	endowed	310:316	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	5	63	from	fat	1346:1348	arg1	low					1339:1341	low	1339:1341	low	1339:1341	Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a "lean-like phenotype", and polarises gut-specific immune responses mimicking the effect of a diet low in fat and high in polysaccharides content.
30291258	1	64	theme	receptor-α	251:260	arg1	oleoylethanolamide					152:169	The lipid sensor oleoylethanolamide	135:169	The lipid sensor oleoylethanolamide (OEA)	135:175	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	64	theme	receptor-α	251:260	arg1	agonist					206:212	an endogenous high-affinity agonist	178:212	an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine	178:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	65	theme	distinctive	331:341	arg1	properties					355:364	several distinctive homeostatic properties	323:364	several distinctive homeostatic properties	323:364	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	65	theme	distinctive	331:341	arg1	control					375:381	control	375:381	control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation	375:472	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	4	66	theme	first	779:783	arg1	time					785:788	the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet	775:862	the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet	775:862	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
30291258	3	67	theme	OEA	698:700	arg1	effect					688:693	an unexplored modulatory effect	663:693	an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response	663:752	Here we report an unexplored modulatory effect of OEA on the intestinal microbiota and on immune response.
30291258	1	68	theme	sensor	145:150	arg1	agonist					206:212	an endogenous high-affinity agonist	178:212	an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine	178:304	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	68	theme	sensor	145:150	arg1	OEA					172:174	OEA	172:174	OEA	172:174	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	68	theme	sensor	145:150	arg1	oleoylethanolamide					152:169	The lipid sensor oleoylethanolamide	135:169	The lipid sensor oleoylethanolamide (OEA)	135:175	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	1	68	theme	sensor	145:150	arg1	endowed					310:316	endowed	310:316	endowed	310:316	The lipid sensor oleoylethanolamide (OEA), an endogenous high-affinity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-inflammatory activity, stimulation of lipolysis and fatty acid oxidation.
30291258	4	69	from	ratio	942:946	arg1	favour					951:956	favour	951:956	favour of Bacteroidetes (in particular Bacteroides genus)	951:1007	Our study shows for the first time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota profile, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer's patches.
31471298	1	0	theme	unique	244:249	arg1	feature					251:257	a unique feature	242:257	a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains)	242:350	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	9	1	theme	N-linked	1625:1632	arg1	sites					1648:1652	N-linked glycosylation sites	1625:1652	N-linked glycosylation sites	1625:1652	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	8	2	from	ACPA-IgG	1504:1511	arg1	presence					1472:1479	the presence	1468:1479	the presence of V-domain glycans on ACPA-IgG	1468:1511	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	6	3	theme	V-domain	880:887	arg1	glycosylation					889:901	METHODS ACPA-IgG V-domain glycosylation	863:901	METHODS ACPA-IgG V-domain glycosylation	863:901	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	9	4	theme	sites	1648:1652	arg1	incorporation					1608:1620	the incorporation	1604:1620	the incorporation of N-linked glycosylation sites	1604:1652	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	9	4	theme	sites	1648:1652	arg1	glycans					1680:1686	V-domain glycans	1671:1686	V-domain glycans	1671:1686	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	7	5	from	glycans	1218:1224	arg1	ACPA-IgG					1229:1236	ACPA-IgG	1229:1236	ACPA-IgG	1229:1236	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	6	6	theme	RA	1143:1144	arg1	patients					1146:1153	RA patients	1143:1153	RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative)	1143:1198	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	5	7	attach	presence	759:766	arg2	glycans					789:795	ACPA-IgG V-domain glycans	771:795	ACPA-IgG V-domain glycans	771:795	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	5	7	attach	presence	759:766	arg1	samples					807:813	paired samples	800:813	paired samples of pre-symptomatic individuals and RA patients	800:860	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	5	8	theme	RA	850:851	arg1	patients					853:860	RA patients	850:860	RA patients	850:860	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	6	9	theme	METHODS	863:869	arg1	glycosylation					889:901	METHODS ACPA-IgG V-domain glycosylation	863:901	METHODS ACPA-IgG V-domain glycosylation	863:901	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	4	10	theme	glycans	658:664	arg1	generation					635:644	the generation	631:644	the generation of V-domain glycans	631:664	Further, it is unknown which factors might trigger the generation of V-domain glycans and whether such glycans are relevant for the transition towards RA.
31471298	7	11	theme	symptom	1360:1366	arg1	onset					1368:1372	symptom onset	1360:1372	symptom onset	1360:1372	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	1	12	theme	rheumatoid	199:208	arg1	RA					221:222	RA	221:222	RA	221:222	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	1	12	theme	rheumatoid	199:208	arg1	arthritis					210:218	rheumatoid arthritis	199:218	rheumatoid arthritis (RA) patients	199:232	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	8	13	theme	class	1411:1415	arg1	alleles					1444:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	0	14	theme	rheumatoid	119:128	arg1	arthritis					130:138	rheumatoid arthritis	119:138	rheumatoid arthritis	119:138	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	5	15	theme	individuals	834:844	arg1	samples					807:813	paired samples	800:813	paired samples of pre-symptomatic individuals and RA patients	800:860	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	8	16	theme	shared	1420:1425	arg1	alleles					1444:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	9	17	dep	CONCLUSION	1514:1523	arg1	indicate					1542:1549	indicate	1542:1549	indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life	1542:1779	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	6	18	theme	performance	933:943	arg1	chromatography					952:965	ultra-high performance liquid chromatography	922:965	ultra-high performance liquid chromatography (UHPLC)	922:973	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	18	theme	performance	933:943	arg1	UHPLC					968:972	UHPLC	968:972	UHPLC	968:972	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	9	19	theme	symptom	1717:1723	arg1	onset					1725:1729	symptom onset	1717:1729	symptom onset in individuals that will develop RA later in life	1717:1779	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	6	20	theme	interquartile	1032:1044	arg1	IQR					1053:1055	IQR	1053:1055	IQR	1053:1055	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	20	theme	interquartile	1032:1044	arg1	range					1046:1050	median interquartile range	1025:1050	median interquartile range (IQR) pre-dating time	1025:1072	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	7	21	theme	pre-symptomatic	1292:1306	arg1	individuals					1308:1318	pre-symptomatic individuals	1292:1318	pre-symptomatic individuals	1292:1318	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	9	22	link	N-linked	1625:1632	arg1	sites					1648:1652	N-linked glycosylation sites	1625:1652	N-linked glycosylation sites	1625:1652	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	10	23	theme	ACPA-positive	2000:2012	arg1	RA					2014:2015	ACPA-positive RA	2000:2015	ACPA-positive RA	2000:2015	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	0	24	theme	variable	47:54	arg1	glycosylation					63:75	ACPA-IgG variable domain glycosylation	38:75	ACPA-IgG variable domain glycosylation	38:75	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	1	25	from	antibodies	178:187	arg1	patients					225:232	rheumatoid arthritis (RA) patients	199:232	rheumatoid arthritis (RA) patients	199:232	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	1	26	theme	OBJECTIVE	141:149	arg1	ACPA					190:193	ACPA	190:193	ACPA	190:193	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	1	26	theme	OBJECTIVE	141:149	arg1	antibodies					178:187	OBJECTIVE Anti-citrullinated protein antibodies	141:187	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients	141:232	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	0	27	from	presence	7:14	arg1	phase					84:88	the phase	80:88	the phase preceding the development of rheumatoid arthritis	80:138	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	0	28	theme	glycosylation	63:75	arg1	presence					7:14	the presence	3:14	the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis	3:138	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	1	29	theme	protein	170:176	arg1	ACPA					190:193	ACPA	190:193	ACPA	190:193	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	1	29	theme	protein	170:176	arg1	antibodies					178:187	OBJECTIVE Anti-citrullinated protein antibodies	141:187	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients	141:232	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	6	30	theme	pre-symptomatic	996:1010	arg1	individuals					1012:1022	pre-symptomatic individuals	996:1022	pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative)	996:1137	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	2	31	gly	N-glycosylation	378:392	arg2	sites					394:398	N-glycosylation sites	378:398	N-glycosylation sites	378:398	Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation.
31471298	10	32	gly	glycosylation	1881:1893	arg1	phase					1914:1918	the pre-disease phase	1898:1918	the pre-disease phase	1898:1918	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	9	33	from	onset	1725:1729	arg1	individuals					1734:1744	individuals	1734:1744	individuals that will develop RA later in life	1734:1779	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	8	34	theme	glycans	1493:1499	arg1	presence					1472:1479	the presence	1468:1479	the presence of V-domain glycans on ACPA-IgG	1468:1511	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	5	35	theme	glycans	789:795	arg1	presence					759:766	the presence	755:766	the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients	755:860	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	7	36	dep	RESULTS	1201:1207	arg1	increased					1340:1348	increased	1340:1348	increased closer to symptom onset	1340:1372	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	7	36	dep	RESULTS	1201:1207	arg1	present					1251:1257	present	1251:1257	present	1251:1257	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	5	37	theme	paired	800:805	arg1	samples					807:813	paired samples	800:813	paired samples of pre-symptomatic individuals and RA patients	800:860	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	1	38	theme	abundant	274:281	arg1	presence					283:290	the abundant presence	270:290	the abundant presence of N-linked glycans within the variable domains (V-domains)	270:350	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	9	39	theme	somatic	1556:1562	arg1	hypermutation					1564:1576	somatic hypermutation	1556:1576	somatic hypermutation	1556:1576	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	2	40	theme	glycans	454:460	arg1	incorporation					428:440	the incorporation	424:440	the incorporation of V-domain glycans	424:460	Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation.
31471298	10	41	theme	HLA-SE	1833:1838	arg1	alleles					1840:1846	HLA-SE alleles	1833:1846	HLA-SE alleles	1833:1846	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	8	42	from	glycans	1493:1499	arg1	ACPA-IgG					1504:1511	ACPA-IgG	1504:1511	ACPA-IgG	1504:1511	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	0	43	theme	HLA-SE	19:24	arg1	alleles					26:32	HLA-SE alleles	19:32	HLA-SE alleles	19:32	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	7	44	from	present	1251:1257	arg1	individuals					1308:1318	pre-symptomatic individuals	1292:1318	pre-symptomatic individuals	1292:1318	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	7	45	attach	present	1251:1257	arg2	glycans					1218:1224	V-domain glycans	1209:1224	V-domain glycans on ACPA-IgG	1209:1236	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	7	45	attach	present	1251:1257	arg1	individuals					1308:1318	pre-symptomatic individuals	1292:1318	pre-symptomatic individuals	1292:1318	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	5	46	theme	ACPA-IgG	771:778	arg1	glycans					789:795	ACPA-IgG V-domain glycans	771:795	ACPA-IgG V-domain glycans	771:795	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	1	47	theme	glycans	304:310	arg1	presence					283:290	the abundant presence	270:290	the abundant presence of N-linked glycans within the variable domains (V-domains)	270:350	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	10	48	theme	ACPA-IgG	1863:1870	arg1	glycosylation					1881:1893	ACPA-IgG V-domain glycosylation	1863:1893	ACPA-IgG V-domain glycosylation in the pre-disease phase	1863:1918	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	8	49	theme	human	1387:1391	arg1	class					1411:1415	human leucocyte antigen class II	1387:1418	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	1	50	link	N-linked	295:302	arg1	glycans					304:310	N-linked glycans	295:310	N-linked glycans within the variable domains (V-domains)	295:350	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	10	51	dep	associate	1848:1856	arg1	refine					1940:1945	refine	1940:1945	refine the connection between HLA-SE and the development of ACPA-positive RA	1940:2015	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	8	52	theme	antigen	1403:1409	arg1	class					1411:1415	human leucocyte antigen class II	1387:1418	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	6	53	theme	ultra-high	922:931	arg1	chromatography					952:965	ultra-high performance liquid chromatography	922:965	ultra-high performance liquid chromatography (UHPLC)	922:973	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	53	theme	ultra-high	922:931	arg1	UHPLC					968:972	UHPLC	968:972	UHPLC	968:972	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	7	54	dep	15	1265:1266	arg1	to					1262:1263	to	1262:1263	to	1262:1263	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	9	55	theme	glycosylation	1634:1646	arg1	sites					1648:1652	N-linked glycosylation sites	1625:1652	N-linked glycosylation sites	1625:1652	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	0	56	attach	presence	7:14	arg1	phase					84:88	the phase	80:88	the phase preceding the development of rheumatoid arthritis	80:138	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	0	56	attach	presence	7:14	arg2	alleles					26:32	HLA-SE alleles	19:32	HLA-SE alleles	19:32	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	0	56	attach	presence	7:14	arg2	glycosylation					63:75	ACPA-IgG variable domain glycosylation	38:75	ACPA-IgG variable domain glycosylation	38:75	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	6	57	theme	patients	1146:1153	arg1	samples					985:991	paired samples	978:991	paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative)	978:1198	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	58	theme	ACPA-IgG	871:878	arg1	glycosylation					889:901	METHODS ACPA-IgG V-domain glycosylation	863:901	METHODS ACPA-IgG V-domain glycosylation	863:901	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	3	59	theme	V-domain	549:556	arg1	glycosylation					558:570	V-domain glycosylation	549:570	V-domain glycosylation	549:570	However, it is currently unclear when V-domain glycosylation occurs.
31471298	5	60	theme	patients	853:860	arg1	samples					807:813	paired samples	800:813	paired samples of pre-symptomatic individuals and RA patients	800:860	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	10	61	from	glycosylation	1881:1893	arg1	phase					1914:1918	the pre-disease phase	1898:1918	the pre-disease phase	1898:1918	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	6	62	theme	paired	978:983	arg1	samples					985:991	paired samples	978:991	paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative)	978:1198	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	9	63	theme	V-domain	1671:1678	arg1	glycans					1680:1686	V-domain glycans	1671:1686	V-domain glycans	1671:1686	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	4	64	theme	V-domain	649:656	arg1	glycans					658:664	V-domain glycans	649:664	V-domain glycans	649:664	Further, it is unknown which factors might trigger the generation of V-domain glycans and whether such glycans are relevant for the transition towards RA.
31471298	0	65	theme	arthritis	130:138	arg1	development					104:114	the development	100:114	the development of rheumatoid arthritis	100:138	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	5	66	theme	pre-symptomatic	818:832	arg1	individuals					834:844	pre-symptomatic individuals	818:844	pre-symptomatic individuals	818:844	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	8	67	theme	epitope	1427:1433	arg1	alleles					1444:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	6	68	dep	patients	1146:1153	arg1	94					1162:1163	94	1162:1163	94	1162:1163	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	7	69	located	present	1251:1257	arg2	glycans					1218:1224	V-domain glycans	1209:1224	V-domain glycans on ACPA-IgG	1209:1236	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	7	69	located	present	1251:1257	arg1	individuals					1308:1318	pre-symptomatic individuals	1292:1318	pre-symptomatic individuals	1292:1318	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	6	70	theme	liquid	945:950	arg1	chromatography					952:965	ultra-high performance liquid chromatography	922:965	ultra-high performance liquid chromatography (UHPLC)	922:973	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	70	theme	liquid	945:950	arg1	UHPLC					968:972	UHPLC	968:972	UHPLC	968:972	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	8	71	theme	HLA-SE	1436:1441	arg1	alleles					1444:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	10	72	theme	first	1813:1817	arg1	evidence					1819:1826	first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA	1813:2015	first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA	1813:2015	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	10	73	theme	RA	2014:2015	arg1	HLA-SE					1970:1975	HLA-SE	1970:1975	HLA-SE	1970:1975	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	10	73	theme	RA	2014:2015	arg1	development					1985:1995	the development	1981:1995	the development of ACPA-positive RA	1981:2015	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	0	74	theme	domain	56:61	arg1	glycosylation					63:75	ACPA-IgG variable domain glycosylation	38:75	ACPA-IgG variable domain glycosylation	38:75	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	6	75	theme	median	1025:1030	arg1	IQR					1053:1055	IQR	1053:1055	IQR	1053:1055	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	75	theme	median	1025:1030	arg1	range					1046:1050	median interquartile range	1025:1050	median interquartile range (IQR) pre-dating time	1025:1072	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	1	76	theme	variable	323:330	arg1	domains					332:338	the variable domains	319:338	the variable domains (V-domains)	319:350	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	1	76	theme	variable	323:330	arg1	V-domains					341:349	V-domains	341:349	V-domains	341:349	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	1	77	theme	Anti-citrullinated	151:168	arg1	ACPA					190:193	ACPA	190:193	ACPA	190:193	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	1	77	theme	Anti-citrullinated	151:168	arg1	antibodies					178:187	OBJECTIVE Anti-citrullinated protein antibodies	141:187	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients	141:232	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	6	78	theme	individuals	1012:1022	arg1	samples					985:991	paired samples	978:991	paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative)	978:1198	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	79	dep	individuals	1012:1022	arg1	IQR					1053:1055	IQR	1053:1055	IQR	1053:1055	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	79	dep	individuals	1012:1022	arg1	range					1046:1050	median interquartile range	1025:1050	median interquartile range (IQR) pre-dating time	1025:1072	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	4	80	theme	such	678:681	arg1	glycans					683:689	such glycans	678:689	such glycans	678:689	Further, it is unknown which factors might trigger the generation of V-domain glycans and whether such glycans are relevant for the transition towards RA.
31471298	5	81	from	presence	759:766	arg1	samples					807:813	paired samples	800:813	paired samples of pre-symptomatic individuals and RA patients	800:860	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	8	82	theme	V-domain	1484:1491	arg1	glycans					1493:1499	V-domain glycans	1484:1499	V-domain glycans on ACPA-IgG	1484:1511	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	9	83	dep	years	1704:1708	arg1	onset					1725:1729	symptom onset	1717:1729	symptom onset in individuals that will develop RA later in life	1717:1779	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	7	84	from	individuals	1308:1318	arg1	present					1251:1257	present	1251:1257	present	1251:1257	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	2	85	theme	somatic	488:494	arg1	hypermutation					496:508	somatic hypermutation	488:508	somatic hypermutation	488:508	Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation.
31471298	6	86	dep	range	1046:1050	arg1	years					1085:1089	5.8 (5.9) years	1075:1089	5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative	1075:1136	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	86	dep	range	1046:1050	arg1	time					1069:1072	pre-dating time	1058:1072	median interquartile range (IQR) pre-dating time	1025:1072	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	5	87	theme	V-domain	780:787	arg1	glycans					789:795	ACPA-IgG V-domain glycans	771:795	ACPA-IgG V-domain glycans	771:795	Here, we determined the presence of ACPA-IgG V-domain glycans in paired samples of pre-symptomatic individuals and RA patients.
31471298	6	88	theme	pre-dating	1058:1067	arg1	time					1069:1072	pre-dating time	1058:1072	median interquartile range (IQR) pre-dating time	1025:1072	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	0	89	theme	alleles	26:32	arg1	presence					7:14	the presence	3:14	the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis	3:138	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	1	90	theme	arthritis	210:218	arg1	patients					225:232	rheumatoid arthritis (RA) patients	199:232	rheumatoid arthritis (RA) patients	199:232	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	7	91	dep	years	1268:1272	arg1	disease					1281:1287	disease	1281:1287	disease	1281:1287	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	2	92	theme	V-domain	445:452	arg1	glycans					454:460	V-domain glycans	445:460	V-domain glycans	445:460	Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation.
31471298	2	93	theme	N-glycosylation	378:392	arg1	sites					394:398	N-glycosylation sites	378:398	N-glycosylation sites	378:398	Recently, we showed that N-glycosylation sites, which are required for the incorporation of V-domain glycans, are introduced following somatic hypermutation.
31471298	0	94	theme	ACPA-IgG	38:45	arg1	glycosylation					63:75	ACPA-IgG variable domain glycosylation	38:75	ACPA-IgG variable domain glycosylation	38:75	On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis.
31471298	1	95	theme	N-linked	295:302	arg1	glycans					304:310	N-linked glycans	295:310	N-linked glycans within the variable domains (V-domains)	295:350	OBJECTIVE Anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients display a unique feature defined by the abundant presence of N-linked glycans within the variable domains (V-domains).
31471298	9	96	theme	ACPA	1581:1584	arg1	hypermutation					1564:1576	somatic hypermutation	1556:1576	somatic hypermutation	1556:1576	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	10	97	theme	V-domain	1872:1879	arg1	glycosylation					1881:1893	ACPA-IgG V-domain glycosylation	1863:1893	ACPA-IgG V-domain glycosylation in the pre-disease phase	1863:1918	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	6	98	dep	years	1085:1089	arg1	ACPA-negative					1124:1136	ACPA-negative	1124:1136	ACPA-negative	1124:1136	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	98	dep	years	1085:1089	arg1	n=201					1092:1096	n=201	1092:1096	5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative	1075:1136	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	6	98	dep	years	1085:1089	arg1	ACPA-positive					1103:1115	ACPA-positive	1103:1115	ACPA-positive	1103:1115	METHODS ACPA-IgG V-domain glycosylation was analysed using ultra-high performance liquid chromatography (UHPLC) in paired samples of pre-symptomatic individuals (median interquartile range (IQR) pre-dating time: 5.8 (5.9) years; n=201; 139 ACPA-positive and 62 ACPA-negative) and RA patients (n=99; 94 ACPA-positive and 5 ACPA-negative).
31471298	9	99	gly	glycosylation	1634:1646	arg2	sites					1648:1652	N-linked glycosylation sites	1625:1652	N-linked glycosylation sites	1625:1652	CONCLUSION Our observations indicate that somatic hypermutation of ACPA, which results in the incorporation of N-linked glycosylation sites and consequently V-domain glycans, occurs already years before symptom onset in individuals that will develop RA later in life.
31471298	7	100	theme	V-domain	1209:1216	arg1	glycans					1218:1224	V-domain glycans	1209:1224	V-domain glycans on ACPA-IgG	1209:1236	RESULTS V-domain glycans on ACPA-IgG were already present up to 15 years before disease in pre-symptomatic individuals and their abundance increased closer to symptom onset.
31471298	10	101	theme	pre-disease	1902:1912	arg1	phase					1914:1918	the pre-disease phase	1898:1918	the pre-disease phase	1898:1918	Moreover, our findings provide first evidence that HLA-SE alleles associate with ACPA-IgG V-domain glycosylation in the pre-disease phase and thereby further refine the connection between HLA-SE and the development of ACPA-positive RA.
31471298	8	102	theme	leucocyte	1393:1401	arg1	class					1411:1415	human leucocyte antigen class II	1387:1418	human leucocyte antigen class II shared epitope (HLA-SE) alleles	1387:1450	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
31471298	8	103	from	presence	1472:1479	arg1	ACPA-IgG					1504:1511	ACPA-IgG	1504:1511	ACPA-IgG	1504:1511	Noteworthy, human leucocyte antigen class II shared epitope (HLA-SE) alleles associated with the presence of V-domain glycans on ACPA-IgG.
29491160	12	0	theme	influenza	2010:2018	arg1	viruses					2020:2026	human influenza viruses	2004:2026	human influenza viruses	2004:2026	Receptor specificity was still markedly different compared to that of human influenza viruses.
29491160	3	1	contain	have	330:333	arg1	groups					323:328	Several research groups	306:328	Several research groups	306:328	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	3	1	contain	have	330:333	arg2	mutations					344:352	reported mutations	335:352	reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets	335:479	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	4	2	theme	human	612:616	arg1	H1N1					618:621	human H1N1	612:621	human H1N1	612:621	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	2	3	theme	human-type	271:280	arg1	receptors					282:290	human-type receptors	271:290	human-type receptors	271:290	Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential.
29491160	9	4	theme	human-type	1664:1673	arg1	receptors					1675:1683	human-type receptors	1664:1683	human-type receptors	1664:1683	Fortunately, H5N1 viruses do not transmit between humans because they do not bind to human-type receptors.
29491160	14	5	theme	specificity	2176:2186	arg1	determinant					2188:2198	a common receptor specificity determinant	2158:2198	a common receptor specificity determinant	2158:2198	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	14	5	theme	specificity	2176:2186	arg1	K193T					2140:2144	K193T	2140:2144	K193T	2140:2144	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	15	6	used	used	2297:2300	arg2	mutation					2277:2284	The K193T mutation	2267:2284	The K193T mutation	2267:2284	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	15	6	used	used	2297:2300	arg2	marker					2307:2312	a marker	2305:2312	a marker during surveillance of emerging viruses	2305:2352	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	5	7	theme	hemagglutinin	884:896	arg1	trimer					903:908	the same hemagglutinin (HA) trimer	875:908	the same hemagglutinin (HA) trimer	875:908	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	8	8	theme	K193T	1213:1217	arg1	mutation					1219:1226	the K193T mutation	1209:1226	the K193T mutation	1209:1226	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	14	9	theme	common	2160:2165	arg1	determinant					2188:2198	a common receptor specificity determinant	2158:2198	a common receptor specificity determinant	2158:2198	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	14	9	theme	common	2160:2165	arg1	K193T					2140:2144	K193T	2140:2144	K193T	2140:2144	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	15	10	theme	emerging	2337:2344	arg1	viruses					2346:2352	emerging viruses	2337:2352	emerging viruses	2337:2352	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	3	11	from	mutations	344:352	arg1	viruses					362:368	H5N1 viruses	357:368	H5N1 viruses	357:368	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	8	12	theme	influenza	1437:1445	arg1	Infections					1466:1475	human influenza viruses.IMPORTANCE Infections	1431:1475	human influenza viruses.IMPORTANCE Infections	1431:1475	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	8	13	theme	H5	1235:1236	arg1	HA					1238:1239	the H5 HA	1231:1239	the H5 HA of a respiratory-droplet-transmissible virus	1231:1284	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	13	14	from	mutation	2058:2065	arg1	H5N1					2091:2094	ferret-transmissible H5N1	2070:2094	ferret-transmissible H5N1	2070:2094	Here we report an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding.
29491160	5	15	theme	branched	763:770	arg1	glycans					781:787	α2-6-sialylated branched N-linked glycans	747:787	α2-6-sialylated branched N-linked glycans	747:787	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	13	16	theme	receptor	2122:2129	arg1	binding					2131:2137	human-type receptor binding	2111:2137	human-type receptor binding	2111:2137	Here we report an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding.
29491160	5	17	theme	influenza	706:714	arg1	viruses					716:722	human influenza viruses	700:722	human influenza viruses	700:722	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	5	18	from	acids	807:811	arg1	branch					821:826	each branch	816:826	each branch	816:826	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	11	19	theme	human-type	1912:1921	arg1	receptors					1923:1931	human-type receptors	1912:1931	human-type receptors	1912:1931	Receptor binding, among others, was changed, and the viruses now bind to human-type receptors.
29491160	8	20	theme	avian	1480:1484	arg1	viruses					1491:1497	avian H5N1 viruses	1480:1497	avian H5N1 viruses are associated with a high mortality rate in several species, including humans	1480:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	8	21	theme	respiratory-droplet-transmissible	1246:1278	arg1	virus					1280:1284	a respiratory-droplet-transmissible virus	1244:1284	a respiratory-droplet-transmissible virus	1244:1284	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	10	22	theme	influenza	1812:1820	arg1	infection					1828:1836	influenza virus infection	1812:1836	influenza virus infection	1812:1836	In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection.
29491160	15	23	theme	pandemic	2374:2381	arg1	risk					2383:2386	potential pandemic risk	2364:2386	potential pandemic risk	2364:2386	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	1	24	theme	avian	140:144	arg1	viruses					156:162	avian influenza viruses	140:162	avian influenza viruses	140:162	All human influenza pandemics have originated from avian influenza viruses.
29491160	5	25	theme	sialic	800:805	arg1	acids					807:811	the sialic acids	796:811	the sialic acids on each branch	796:826	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	5	26	theme	trimer	903:908	arg1	protomers					862:870	two protomers	858:870	two protomers of the same hemagglutinin (HA) trimer	858:908	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	6	27	theme	receptor-binding	990:1005	arg1	pocket					1007:1012	the receptor-binding pocket	986:1012	the receptor-binding pocket	986:1012	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	3	28	theme	research	314:321	arg1	groups					323:328	Several research groups	306:328	Several research groups	306:328	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	13	29	theme	additional	2047:2056	arg1	mutation					2058:2065	an additional mutation	2044:2065	an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding	2044:2137	Here we report an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding.
29491160	3	30	theme	H5N1	357:360	arg1	viruses					362:368	H5N1 viruses	357:368	H5N1 viruses	357:368	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	5	31	from	sites	849:853	arg1	protomers					862:870	two protomers	858:870	two protomers of the same hemagglutinin (HA) trimer	858:908	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	8	32	theme	mortality	1526:1534	arg1	rate					1536:1539	a high mortality rate	1519:1539	a high mortality rate in several species, including humans	1519:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	6	33	from	top	979:981	arg1	helix					966:970	the 190 helix	958:970	the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193	958:1084	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	8	34	theme	trachea	1330:1336	arg1	cells					1349:1353	human trachea epithelial cells	1324:1353	human trachea epithelial cells	1324:1353	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	7	35	theme	branched	1156:1163	arg1	receptors					1174:1182	branched N-linked receptors	1156:1182	branched N-linked receptors	1156:1182	Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors.
29491160	3	36	theme	respiratory	432:442	arg1	transmission					452:463	respiratory droplet transmission	432:463	respiratory droplet transmission between ferrets	432:479	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	5	37	theme	receptor	840:847	arg1	sites					849:853	receptor sites	840:853	receptor sites on two protomers of the same hemagglutinin (HA) trimer	840:908	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	15	38	theme	K193T	2271:2275	arg1	marker					2307:2312	a marker	2305:2312	a marker during surveillance of emerging viruses	2305:2352	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	15	38	theme	K193T	2271:2275	arg1	mutation					2277:2284	The K193T mutation	2267:2284	The K193T mutation	2267:2284	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	1	39	theme	human	93:97	arg1	pandemics					109:117	All human influenza pandemics	89:117	All human influenza pandemics	89:117	All human influenza pandemics have originated from avian influenza viruses.
29491160	4	40	theme	fine	574:577	arg1	specificity					588:598	fine receptor specificity	574:598	fine receptor specificity compared to human H1N1 and H3N2	574:630	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	14	41	theme	multiple	2248:2255	arg1	subtypes					2257:2264	multiple subtypes	2248:2264	multiple subtypes	2248:2264	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	0	42	theme	Receptor	20:27	arg1	Binding					29:35	Human-Type Receptor Binding	9:35	Human-Type Receptor Binding	9:35	Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.
29491160	7	43	link	N-linked	1165:1172	arg1	receptors					1174:1182	branched N-linked receptors	1156:1182	branched N-linked receptors	1156:1182	Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors.
29491160	9	44	theme	H5N1	1592:1595	arg1	viruses					1597:1603	H5N1 viruses	1592:1603	H5N1 viruses	1592:1603	Fortunately, H5N1 viruses do not transmit between humans because they do not bind to human-type receptors.
29491160	14	45	from	binding	2237:2243	arg1	subtypes					2257:2264	multiple subtypes	2248:2264	multiple subtypes	2248:2264	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	8	46	theme	extended	1375:1382	arg1	glycans					1409:1415	extended α2-6-sialylated N-linked glycans	1375:1415	extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans	1375:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	7	47	theme	K193T	1116:1120	arg1	mutation					1122:1129	a K193T mutation	1114:1129	a K193T mutation	1114:1129	Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors.
29491160	4	48	from	differences	559:569	arg1	specificity					588:598	fine receptor specificity	574:598	fine receptor specificity compared to human H1N1 and H3N2	574:630	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	3	49	theme	human-type	399:408	arg1	receptors					410:418	human-type receptors	399:418	human-type receptors	399:418	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	2	50	theme	multiple	174:181	arg1	changes					183:189	multiple changes	174:189	multiple changes	174:189	Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential.
29491160	8	51	theme	N-linked	1400:1407	arg1	glycans					1409:1415	extended α2-6-sialylated N-linked glycans	1375:1415	extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans	1375:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	11	52	theme	Receptor	1839:1846	arg1	binding					1848:1854	Receptor binding	1839:1854	Receptor binding	1839:1854	Receptor binding, among others, was changed, and the viruses now bind to human-type receptors.
29491160	2	53	theme	avian	209:213	arg1	virus					215:219	an avian virus	206:219	an avian virus	206:219	Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential.
29491160	14	54	theme	receptor	2228:2235	arg1	binding					2237:2243	human-type receptor binding	2217:2243	human-type receptor binding in multiple subtypes	2217:2264	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	8	55	theme	human	1431:1435	arg1	Infections					1466:1475	human influenza viruses.IMPORTANCE Infections	1431:1475	human influenza viruses.IMPORTANCE Infections	1431:1475	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	0	56	with	H5N1	61:64	arg1	Mutation					79:86	a K193T Mutation	71:86	a K193T Mutation	71:86	Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.
29491160	8	57	gly	α2-6-sialylated	1384:1398	arg1	glycans					1409:1415	extended α2-6-sialylated N-linked glycans	1375:1415	extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans	1375:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	6	58	from	position	1073:1080	arg1	lysine					1063:1068	lysine	1063:1068	lysine at position 193	1063:1084	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	12	59	theme	human	2004:2008	arg1	viruses					2020:2026	human influenza viruses	2004:2026	human influenza viruses	2004:2026	Receptor specificity was still markedly different compared to that of human influenza viruses.
29491160	6	60	theme	binding	919:925	arg1	mode					927:930	this binding mode	914:930	this binding mode	914:930	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	10	61	theme	seminal	1701:1707	arg1	papers					1709:1714	three seminal papers	1695:1714	three seminal papers	1695:1714	In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection.
29491160	5	62	link	N-linked	772:779	arg1	glycans					781:787	α2-6-sialylated branched N-linked glycans	747:787	α2-6-sialylated branched N-linked glycans	747:787	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	5	63	theme	same	879:882	arg1	hemagglutinin					884:896	same hemagglutinin	879:896	the same hemagglutinin (HA) trimer	875:908	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	5	63	theme	same	879:882	arg1	HA					899:900	HA	899:900	HA	899:900	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	14	64	theme	receptor	2167:2174	arg1	determinant					2188:2198	a common receptor specificity determinant	2158:2198	a common receptor specificity determinant	2158:2198	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	14	64	theme	receptor	2167:2174	arg1	K193T					2140:2144	K193T	2140:2144	K193T	2140:2144	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
29491160	12	65	theme	Receptor	1934:1941	arg1	specificity					1943:1953	Receptor specificity	1934:1953	Receptor specificity	1934:1953	Receptor specificity was still markedly different compared to that of human influenza viruses.
29491160	6	66	theme	190	962:964	arg1	helix					966:970	the 190 helix	958:970	the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193	958:1084	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	8	67	theme	viruses.IMPORTANCE	1447:1464	arg1	Infections					1466:1475	human influenza viruses.IMPORTANCE Infections	1431:1475	human influenza viruses.IMPORTANCE Infections	1431:1475	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	4	68	theme	receptor	654:661	arg1	binding					663:669	avian-type receptor binding	643:669	avian-type receptor binding	643:669	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	5	69	theme	α2-6-sialylated	747:761	arg1	glycans					781:787	α2-6-sialylated branched N-linked glycans	747:787	α2-6-sialylated branched N-linked glycans	747:787	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	13	70	theme	human-type	2111:2120	arg1	binding					2131:2137	human-type receptor binding	2111:2137	human-type receptor binding	2111:2137	Here we report an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding.
29491160	10	71	theme	human	1796:1800	arg1	ferrets					1783:1789	ferrets	1783:1789	ferrets	1783:1789	In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection.
29491160	10	71	theme	human	1796:1800	arg1	model					1802:1806	the human model	1792:1806	the human model for influenza virus infection	1792:1836	In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection.
29491160	4	72	theme	detailed	487:494	arg1	analysis					496:503	detailed analysis	487:503	detailed analysis	487:503	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	5	73	theme	N-linked	772:779	arg1	glycans					781:787	α2-6-sialylated branched N-linked glycans	747:787	α2-6-sialylated branched N-linked glycans	747:787	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	5	74	theme	human	700:704	arg1	viruses					716:722	human influenza viruses	700:722	human influenza viruses	700:722	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	3	75	theme	Several	306:312	arg1	groups					323:328	Several research groups	306:328	Several research groups	306:328	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	8	76	theme	H5N1	1486:1489	arg1	viruses					1491:1497	avian H5N1 viruses	1480:1497	avian H5N1 viruses are associated with a high mortality rate in several species, including humans	1480:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	13	77	theme	ferret-transmissible	2070:2089	arg1	H5N1					2091:2094	ferret-transmissible H5N1	2070:2094	ferret-transmissible H5N1	2070:2094	Here we report an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding.
29491160	10	78	theme	virus	1822:1826	arg1	infection					1828:1836	influenza virus infection	1812:1836	influenza virus infection	1812:1836	In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection.
29491160	8	79	link	N-linked	1400:1407	arg1	glycans					1409:1415	extended α2-6-sialylated N-linked glycans	1375:1415	extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans	1375:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	5	80	gly	α2-6-sialylated	747:761	arg1	glycans					781:787	α2-6-sialylated branched N-linked glycans	747:787	α2-6-sialylated branched N-linked glycans	747:787	We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer.
29491160	0	81	theme	K193T	73:77	arg1	Mutation					79:86	a K193T Mutation	71:86	a K193T Mutation	71:86	Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.
29491160	1	82	theme	influenza	146:154	arg1	viruses					156:162	avian influenza viruses	140:162	avian influenza viruses	140:162	All human influenza pandemics have originated from avian influenza viruses.
29491160	6	83	theme	pocket	1007:1012	arg1	top					979:981	the top	975:981	the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193	975:1084	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	3	84	theme	reported	335:342	arg1	mutations					344:352	reported mutations	335:352	reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets	335:479	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	8	85	theme	virus	1280:1284	arg1	HA					1238:1239	the H5 HA	1231:1239	the H5 HA of a respiratory-droplet-transmissible virus	1231:1284	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	8	86	theme	high	1521:1524	arg1	rate					1536:1539	a high mortality rate	1519:1539	a high mortality rate in several species, including humans	1519:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	15	87	theme	potential	2364:2372	arg1	risk					2383:2386	potential pandemic risk	2364:2386	potential pandemic risk	2364:2386	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	7	88	theme	N-linked	1165:1172	arg1	receptors					1174:1182	branched N-linked receptors	1156:1182	branched N-linked receptors	1156:1182	Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors.
29491160	8	89	theme	mutation	1219:1226	arg1	addition					1197:1204	the addition	1193:1204	the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus	1193:1284	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	8	90	theme	several	1544:1550	arg1	species					1552:1558	several species	1544:1558	several species	1544:1558	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	8	90	theme	several	1544:1550	arg1	humans					1571:1576	humans	1571:1576	humans	1571:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	8	91	theme	human	1324:1328	arg1	cells					1349:1353	human trachea epithelial cells	1324:1353	human trachea epithelial cells	1324:1353	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	0	92	theme	Human-Type	9:18	arg1	Binding					29:35	Human-Type Receptor Binding	9:35	Human-Type Receptor Binding	9:35	Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.
29491160	6	93	theme	stearic	1044:1050	arg1	clash					1052:1056	a stearic clash	1042:1056	a stearic clash with lysine at position 193	1042:1084	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	4	94	theme	receptor	579:586	arg1	specificity					588:598	fine receptor specificity	574:598	fine receptor specificity compared to human H1N1 and H3N2	574:630	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	8	95	theme	epithelial	1338:1347	arg1	cells					1349:1353	human trachea epithelial cells	1324:1353	human trachea epithelial cells	1324:1353	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	3	96	theme	droplet	444:450	arg1	transmission					452:463	respiratory droplet transmission	432:463	respiratory droplet transmission between ferrets	432:479	Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets.
29491160	8	97	dep	viruses	1491:1497	arg1	associated					1503:1512	associated	1503:1512	are associated with a high mortality rate in several species, including humans	1499:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	1	98	theme	influenza	99:107	arg1	pandemics					109:117	All human influenza pandemics	89:117	All human influenza pandemics	89:117	All human influenza pandemics have originated from avian influenza viruses.
29491160	0	99	theme	Ferret-Transmissible	40:59	arg1	H5N1					61:64	Ferret-Transmissible H5N1	40:64	Ferret-Transmissible H5N1 with a K193T Mutation	40:86	Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.
29491160	4	100	theme	significant	547:557	arg1	differences					559:569	significant differences	547:569	significant differences in fine receptor specificity compared to human H1N1 and H3N2	547:630	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	8	101	from	rate	1536:1539	arg1	species					1552:1558	several species	1544:1558	several species	1544:1558	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	8	101	from	rate	1536:1539	arg1	humans					1571:1576	humans	1571:1576	humans	1571:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	6	102	with	clash	1052:1056	arg1	lysine					1063:1068	lysine	1063:1068	lysine at position 193	1063:1084	In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193.
29491160	15	103	theme	viruses	2346:2352	arg1	surveillance					2321:2332	surveillance	2321:2332	surveillance of emerging viruses	2321:2352	The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
29491160	8	104	theme	α2-6-sialylated	1384:1398	arg1	glycans					1409:1415	extended α2-6-sialylated N-linked glycans	1375:1415	extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans	1375:1576	Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans.
29491160	4	105	theme	avian-type	643:652	arg1	binding					663:669	avian-type receptor binding	643:669	avian-type receptor binding	643:669	Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding.
29491160	14	106	theme	human-type	2217:2226	arg1	binding					2237:2243	human-type receptor binding	2217:2243	human-type receptor binding in multiple subtypes	2217:2264	K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes.
31516090	0	0	theme	mutations	70:78	arg1	role					46:49	role	46:49	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.	0:143	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	0	1	from	infection	11:19	arg1	donors					38:43	Chinese blood donors	24:43	Chinese blood donors	24:43	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	5	2	theme	45	636:637	arg1	B					656:656	45 (46.4%) genotype B	636:656	45 (46.4%) genotype B	636:656	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	6	3	from	groups	737:742	arg1	gene					766:769	the S gene	760:769	the S gene	760:769	Two groups of mutations in the S gene were significantly associated with OBI.
31516090	1	4	theme	Occult	145:150	arg1	infection					170:178	Occult hepatitis B virus infection	145:178	Occult hepatitis B virus infection (OBI)	145:184	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	4	theme	Occult	145:150	arg1	phase					214:218	a low-level asymptomatic phase	189:218	a low-level asymptomatic phase of HBV infection	189:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	4	theme	Occult	145:150	arg1	OBI					181:183	OBI	181:183	OBI	181:183	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	10	5	dep	domains	1296:1302	arg1	TMD1-3					1304:1309	TMD1-3	1304:1309	the S transmembrane domains TMD1-3	1276:1309	The second group included substitutions within the S transmembrane domains TMD1-3.
31516090	1	6	theme	HBV	223:225	arg1	infection					227:235	HBV infection	223:235	HBV infection	223:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	0	7	theme	N-glycosylation	54:68	arg1	mutations					70:78	N-glycosylation mutations	54:78	N-glycosylation mutations	54:78	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	7	8	theme	glycosylation	868:880	arg1	sites					882:886	new N-linked glycosylation sites	855:886	new N-linked glycosylation sites	855:886	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	1	9	theme	hepatitis	152:160	arg1	infection					170:178	Occult hepatitis B virus infection	145:178	Occult hepatitis B virus infection (OBI)	145:184	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	9	theme	hepatitis	152:160	arg1	phase					214:218	a low-level asymptomatic phase	189:218	a low-level asymptomatic phase of HBV infection	189:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	9	theme	hepatitis	152:160	arg1	OBI					181:183	OBI	181:183	OBI	181:183	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	7	10	dep	mutations	836:844	arg1	removing					938:945	removing	938:945	removing the existing one at s146	938:970	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	7	10	dep	mutations	836:844	arg1	creating					846:853	creating	846:853	creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133	846:933	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	1	11	theme	infection	227:235	arg1	phase					214:218	a low-level asymptomatic phase	189:218	a low-level asymptomatic phase of HBV infection	189:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	11	theme	infection	227:235	arg1	infection					170:178	Occult hepatitis B virus infection	145:178	Occult hepatitis B virus infection (OBI)	145:184	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	0	12	theme	amino	84:88	arg1	substitutions					95:107	amino acid substitutions	84:107	amino acid substitutions	84:107	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	4	13	theme	Recombinant	483:493	arg1	HBsAg					495:499	Recombinant HBsAg	483:499	Recombinant HBsAg bearing these mutations	483:523	Recombinant HBsAg bearing these mutations were expressed in vitro and the antigenicity and HBsAg secretion properties were analyzed.
31516090	8	14	theme	varying	1127:1133	arg1	levels					1135:1140	varying levels	1127:1140	varying levels of impaired HBsAg secretion	1127:1168	Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion.
31516090	2	15	theme	relevance	263:271	arg1	Evidence					238:245	Evidence	238:245	Evidence of OBI clinical relevance	238:271	Evidence of OBI clinical relevance is emerging but the mechanisms of its occurrence remain unclear.
31516090	4	16	theme	HBsAg	574:578	arg1	properties					590:599	the antigenicity and HBsAg secretion properties	553:599	the antigenicity and HBsAg secretion properties	553:599	Recombinant HBsAg bearing these mutations were expressed in vitro and the antigenicity and HBsAg secretion properties were analyzed.
31516090	5	17	theme	genotype	670:677	arg1	C					679:679	50 (51.5%) genotype C	659:679	50 (51.5%) genotype C	659:679	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	9	18	theme	production	1209:1218	arg1	pattern					1220:1226	HBsAg production pattern	1203:1226	HBsAg production pattern	1203:1226	N146 mutations had no effect on HBsAg production pattern.
31516090	7	19	theme	new	855:857	arg1	sites					882:886	new N-linked glycosylation sites	855:886	new N-linked glycosylation sites	855:886	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	2	20	theme	clinical	254:261	arg1	relevance					263:271	OBI clinical relevance	250:271	OBI clinical relevance	250:271	Evidence of OBI clinical relevance is emerging but the mechanisms of its occurrence remain unclear.
31516090	6	21	from	mutations	747:755	arg1	gene					766:769	the S gene	760:769	the S gene	760:769	Two groups of mutations in the S gene were significantly associated with OBI.
31516090	0	22	theme	substitutions	95:107	arg1	role					46:49	role	46:49	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.	0:143	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	7	23	theme	N-linked	859:866	arg1	sites					882:886	new N-linked glycosylation sites	855:886	new N-linked glycosylation sites	855:886	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	2	24	theme	OBI	250:252	arg1	relevance					263:271	OBI clinical relevance	250:271	OBI clinical relevance	250:271	Evidence of OBI clinical relevance is emerging but the mechanisms of its occurrence remain unclear.
31516090	8	25	theme	secretion	1160:1168	arg1	levels					1135:1140	varying levels	1127:1140	varying levels of impaired HBsAg secretion	1127:1168	Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion.
31516090	1	26	theme	B	162:162	arg1	infection					170:178	Occult hepatitis B virus infection	145:178	Occult hepatitis B virus infection (OBI)	145:184	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	26	theme	B	162:162	arg1	phase					214:218	a low-level asymptomatic phase	189:218	a low-level asymptomatic phase of HBV infection	189:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	26	theme	B	162:162	arg1	OBI					181:183	OBI	181:183	OBI	181:183	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	0	27	theme	acid	90:93	arg1	substitutions					95:107	amino acid substitutions	84:107	amino acid substitutions	84:107	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	4	28	theme	antigenicity	557:568	arg1	properties					590:599	the antigenicity and HBsAg secretion properties	553:599	the antigenicity and HBsAg secretion properties	553:599	Recombinant HBsAg bearing these mutations were expressed in vitro and the antigenicity and HBsAg secretion properties were analyzed.
31516090	4	29	theme	secretion	580:588	arg1	properties					590:599	the antigenicity and HBsAg secretion properties	553:599	the antigenicity and HBsAg secretion properties	553:599	Recombinant HBsAg bearing these mutations were expressed in vitro and the antigenicity and HBsAg secretion properties were analyzed.
31516090	1	30	theme	virus	164:168	arg1	infection					170:178	Occult hepatitis B virus infection	145:178	Occult hepatitis B virus infection (OBI)	145:184	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	30	theme	virus	164:168	arg1	phase					214:218	a low-level asymptomatic phase	189:218	a low-level asymptomatic phase of HBV infection	189:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	30	theme	virus	164:168	arg1	OBI					181:183	OBI	181:183	OBI	181:183	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	0	31	theme	HBV	7:9	arg1	infection					11:19	Occult HBV infection	0:19	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.	0:143	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	3	32	theme	confirmed	389:397	arg1	OBI					399:401	97 confirmed OBI	386:401	97 confirmed OBI from Chinese blood donors	386:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	0	33	theme	Occult	0:5	arg1	infection					11:19	Occult HBV infection	0:19	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.	0:143	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	8	34	theme	impaired	1145:1152	arg1	secretion					1160:1168	impaired HBsAg secretion	1145:1168	impaired HBsAg secretion	1145:1168	Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion.
31516090	12	35	theme	OBI	1536:1538	arg1	occurrence					1522:1531	the multifactorial occurrence	1503:1531	the multifactorial occurrence of OBI	1503:1538	These mutations appear to be rare and mostly strain specific but they may contribute to the multifactorial occurrence of OBI.
31516090	3	36	theme	OBI	399:401	arg1	characteristics					367:381	the molecular characteristics	353:381	the molecular characteristics of 97 confirmed OBI from Chinese blood donors	353:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	6	37	from	gene	766:769	arg1	mutations					747:755	mutations	747:755	mutations in the S gene	747:769	Two groups of mutations in the S gene were significantly associated with OBI.
31516090	6	37	from	gene	766:769	arg1	groups					737:742	Two groups	733:742	Two groups of mutations in the S gene	733:769	Two groups of mutations in the S gene were significantly associated with OBI.
31516090	0	38	theme	S	112:112	arg1	domains					136:142	S protein transmembrane domains	112:142	S protein transmembrane domains	112:142	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	11	39	theme	Only	1312:1315	arg1	C90R					1349:1352	C90R	1349:1352	C90R	1349:1352	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	11	39	theme	Only	1312:1315	arg1	L88R					1339:1342	L88R	1339:1342	L88R	1339:1342	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	11	39	theme	Only	1312:1315	arg1	mutations					1317:1325	Only mutations	1312:1325	Only mutations C85R, L87R, L88R, and C90R within TMD2	1312:1364	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	11	39	theme	Only	1312:1315	arg1	L87R					1333:1336	L87R	1333:1336	L87R	1333:1336	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	5	40	theme	genotype	695:702	arg1	D					704:704	2 (2.1%) genotype D	686:704	2 (2.1%) genotype D	686:704	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	7	41	dep	positions	891:899	arg1	s116					901:904	s116	901:904	s116	901:904	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	7	41	dep	positions	891:899	arg1	s130					913:916	s130	913:916	s130	913:916	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	7	41	dep	positions	891:899	arg1	s131					923:926	s131	923:926	s131	923:926	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	7	41	dep	positions	891:899	arg1	s123					907:910	s123	907:910	s123	907:910	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	7	41	dep	positions	891:899	arg1	positions					891:899	positions s116, s123, s130, and s131 + s133	891:933	positions s116, s123, s130, and s131 + s133	891:933	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	11	42	theme	HBsAg	1397:1401	arg1	production					1403:1412	defective HBsAg production	1387:1412	defective HBsAg production	1387:1412	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	11	43	dep	mutations	1317:1325	arg1	mutations					1317:1325	Only mutations	1312:1325	Only mutations C85R, L87R, L88R, and C90R within TMD2	1312:1364	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	11	43	dep	mutations	1317:1325	arg1	L88R					1339:1342	L88R	1339:1342	L88R	1339:1342	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	11	43	dep	mutations	1317:1325	arg1	C90R					1349:1352	C90R	1349:1352	C90R	1349:1352	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	11	43	dep	mutations	1317:1325	arg1	L87R					1333:1336	L87R	1333:1336	L87R	1333:1336	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	0	44	theme	blood	32:36	arg1	donors					38:43	Chinese blood donors	24:43	Chinese blood donors	24:43	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	12	45	theme	multifactorial	1507:1520	arg1	occurrence					1522:1531	the multifactorial occurrence	1503:1531	the multifactorial occurrence of OBI	1503:1538	These mutations appear to be rare and mostly strain specific but they may contribute to the multifactorial occurrence of OBI.
31516090	0	46	theme	transmembrane	122:134	arg1	domains					136:142	S protein transmembrane domains	112:142	S protein transmembrane domains	112:142	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	6	47	theme	S	764:764	arg1	gene					766:769	the S gene	760:769	the S gene	760:769	Two groups of mutations in the S gene were significantly associated with OBI.
31516090	8	48	theme	HBsAg	1154:1158	arg1	secretion					1160:1168	impaired HBsAg secretion	1145:1168	impaired HBsAg secretion	1145:1168	Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion.
31516090	3	49	theme	blood	416:420	arg1	donors					422:427	Chinese blood donors	408:427	Chinese blood donors	408:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	0	50	theme	Chinese	24:30	arg1	donors					38:43	Chinese blood donors	24:43	Chinese blood donors	24:43	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	0	51	theme	protein	114:120	arg1	domains					136:142	S protein transmembrane domains	112:142	S protein transmembrane domains	112:142	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	3	52	from	characteristics	367:381	arg1	donors					422:427	Chinese blood donors	408:427	Chinese blood donors	408:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	3	53	theme	molecular	357:365	arg1	characteristics					367:381	the molecular characteristics	353:381	the molecular characteristics of 97 confirmed OBI from Chinese blood donors	353:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	8	54	theme	TCT123-125NCT/NFT	983:999	arg1	Mutations					973:981	Mutations	973:981	Mutations TCT123-125NCT/NFT	973:999	Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion.
31516090	0	55	from	role	46:49	arg1	domains					136:142	S protein transmembrane domains	112:142	S protein transmembrane domains	112:142	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	7	56	gly	glycosylation	868:880	arg2	sites					882:886	new N-linked glycosylation sites	855:886	new N-linked glycosylation sites	855:886	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	3	57	from	donors	422:427	arg1	characteristics					367:381	the molecular characteristics	353:381	the molecular characteristics of 97 confirmed OBI from Chinese blood donors	353:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	3	57	from	donors	422:427	arg1	OBI					399:401	97 confirmed OBI	386:401	97 confirmed OBI from Chinese blood donors	386:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	2	58	theme	occurrence	311:320	arg1	mechanisms					293:302	the mechanisms	289:302	the mechanisms of its occurrence	289:320	Evidence of OBI clinical relevance is emerging but the mechanisms of its occurrence remain unclear.
31516090	5	59	theme	D	704:704	arg1	sequences					706:714	45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences	636:714	45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences	636:714	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	5	60	theme	genotype	647:654	arg1	B					656:656	45 (46.4%) genotype B	636:656	45 (46.4%) genotype B	636:656	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	6	61	theme	mutations	747:755	arg1	mutations					747:755	mutations	747:755	mutations in the S gene	747:769	Two groups of mutations in the S gene were significantly associated with OBI.
31516090	6	61	theme	mutations	747:755	arg1	groups					737:742	Two groups	733:742	Two groups of mutations in the S gene	733:769	Two groups of mutations in the S gene were significantly associated with OBI.
31516090	11	62	theme	defective	1387:1395	arg1	production					1403:1412	defective HBsAg production	1387:1412	defective HBsAg production	1387:1412	Only mutations C85R, L87R, L88R, and C90R within TMD2 were associated with defective HBsAg production.
31516090	5	63	theme	B	656:656	arg1	sequences					706:714	45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences	636:714	45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences	636:714	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	9	64	theme	N146	1171:1174	arg1	mutations					1176:1184	N146 mutations	1171:1184	N146 mutations	1171:1184	N146 mutations had no effect on HBsAg production pattern.
31516090	10	65	theme	second	1233:1238	arg1	group					1240:1244	The second group	1229:1244	The second group	1229:1244	The second group included substitutions within the S transmembrane domains TMD1-3.
31516090	7	66	theme	first	815:819	arg1	group					821:825	The first group	811:825	The first group	811:825	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	1	67	theme	low-level	191:199	arg1	phase					214:218	a low-level asymptomatic phase	189:218	a low-level asymptomatic phase of HBV infection	189:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	67	theme	low-level	191:199	arg1	infection					170:178	Occult hepatitis B virus infection	145:178	Occult hepatitis B virus infection (OBI)	145:184	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	9	68	theme	HBsAg	1203:1207	arg1	pattern					1220:1226	HBsAg production pattern	1203:1226	HBsAg production pattern	1203:1226	N146 mutations had no effect on HBsAg production pattern.
31516090	0	69	dep	infection	11:19	arg1	role					46:49	role	46:49	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.	0:143	Occult HBV infection in Chinese blood donors: role of N-glycosylation mutations and amino acid substitutions in S protein transmembrane domains.
31516090	10	70	theme	transmembrane	1282:1294	arg1	domains					1296:1302	the S transmembrane domains	1276:1302	the S transmembrane domains TMD1-3	1276:1309	The second group included substitutions within the S transmembrane domains TMD1-3.
31516090	3	71	theme	relevant	447:454	arg1	mutations					456:464	relevant mutations	447:464	relevant mutations	447:464	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	1	72	theme	asymptomatic	201:212	arg1	phase					214:218	a low-level asymptomatic phase	189:218	a low-level asymptomatic phase of HBV infection	189:235	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	1	72	theme	asymptomatic	201:212	arg1	infection					170:178	Occult hepatitis B virus infection	145:178	Occult hepatitis B virus infection (OBI)	145:184	Occult hepatitis B virus infection (OBI) is a low-level asymptomatic phase of HBV infection.
31516090	8	73	theme	reduced	1022:1028	arg1	antigenicity					1030:1041	reduced antigenicity	1022:1041	reduced antigenicity	1022:1041	Mutations TCT123-125NCT/NFT were associated with reduced antigenicity, while TST116-118NST, GTS130-132NTS, and TSM131-133NSS/NYT/NST were associated with varying levels of impaired HBsAg secretion.
31516090	10	74	theme	S	1280:1280	arg1	domains					1296:1302	the S transmembrane domains	1276:1302	the S transmembrane domains TMD1-3	1276:1309	The second group included substitutions within the S transmembrane domains TMD1-3.
31516090	3	75	theme	Chinese	408:414	arg1	donors					422:427	Chinese blood donors	408:427	Chinese blood donors	408:427	In this study, the molecular characteristics of 97 confirmed OBI from Chinese blood donors were analyzed and relevant mutations were identified.
31516090	7	76	link	N-linked	859:866	arg1	sites					882:886	new N-linked glycosylation sites	855:886	new N-linked glycosylation sites	855:886	The first group included mutations creating new N-linked glycosylation sites at positions s116, s123, s130, and s131 + s133 or removing the existing one at s146.
31516090	5	77	theme	2	686:686	arg1	D					704:704	2 (2.1%) genotype D	686:704	2 (2.1%) genotype D	686:704	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	5	78	theme	50	659:660	arg1	C					679:679	50 (51.5%) genotype C	659:679	50 (51.5%) genotype C	659:679	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
31516090	9	79	contain	had	1186:1188	arg1	mutations					1176:1184	N146 mutations	1171:1184	N146 mutations	1171:1184	N146 mutations had no effect on HBsAg production pattern.
31516090	9	79	contain	had	1186:1188	arg2	effect					1193:1198	no effect	1190:1198	no effect	1190:1198	N146 mutations had no effect on HBsAg production pattern.
31516090	5	80	theme	C	679:679	arg1	sequences					706:714	45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences	636:714	45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences	636:714	Results showed that 45 (46.4%) genotype B, 50 (51.5%) genotype C, and 2 (2.1%) genotype D sequences were identified.
30600443	4	0	theme	CaV3.1-T-type	540:552	arg1	channel					559:565	the CaV3.1-T-type Ca2+ channel	536:565	the CaV3.1-T-type Ca2+ channel	536:565	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
30600443	5	1	theme	inhibitor	601:609	arg1	tunicamycin					611:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	1	2	theme	cardiovascular	183:196	arg1	system					198:203	the cardiovascular system	179:203	the cardiovascular system particularly for pacemaker activity	179:239	T-type channels are low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity.
30600443	4	3	theme	study	448:452	arg1	aim					436:438	The aim	432:438	The aim of this study	432:452	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
30600443	11	4	theme	plasma	1107:1112	arg1	membrane					1114:1121	the plasma membrane	1103:1121	the plasma membrane	1103:1121	T was insensitive to a glycosidase PNGase F when the channels were expressed on the plasma membrane.
30600443	9	5	from	inactivation	962:973	arg1	recovery					948:955	recovery	948:955	recovery from inactivation	948:973	T was accelerated, and recovery from inactivation was prolonged by tunicamycin (24 h).
30600443	12	6	theme	channel	1246:1252	arg1	expression					1209:1218	the cell surface expression	1192:1218	the cell surface expression of the CaV3.1-T-type Ca2+ channel	1192:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	4	7	theme	channel	559:565	arg1	properties					522:531	the gating properties	511:531	the gating properties of the CaV3.1-T-type Ca2+ channel	511:565	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
30600443	12	8	from	steps	1392:1396	arg1	cell					1405:1408	the cell	1401:1408	the cell	1401:1408	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	7	9	theme	activation	773:782	arg1	curve					784:788	the activation curve	769:788	the activation curve to the depolarization potentials	769:821	Tunicamycin (24 h) significantly shifted the activation curve to the depolarization potentials, whereas the steady-state inactivation curve was unaffected.
30600443	12	10	theme	Ca2+	1241:1244	arg1	channel					1246:1252	the CaV3.1-T-type Ca2+ channel	1223:1252	the CaV3.1-T-type Ca2+ channel	1223:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	3	11	link	N-linked	407:414	arg1	one					381:383	one	381:383	one	381:383	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	3	11	link	N-linked	407:414	arg1	glycosylation					417:429	asparagine-linked (N-linked) glycosylation	388:429	asparagine-linked (N-linked) glycosylation	388:429	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	4	12	theme	gating	515:520	arg1	properties					522:531	the gating properties	511:531	the gating properties of the CaV3.1-T-type Ca2+ channel	511:565	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
30600443	0	13	link	Asparagine-linked	0:16	arg1	glycosylation					18:30	Asparagine-linked glycosylation	0:30	Asparagine-linked glycosylation	0:30	Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel.
30600443	12	14	theme	trafficking	1380:1390	arg1	steps					1392:1396	the folding and trafficking steps	1364:1396	steps	1392:1396	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	12	15	theme	folding	1368:1374	arg1	steps					1392:1396	the folding and trafficking steps	1364:1396	steps	1392:1396	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	3	16	theme	N-linked	407:414	arg1	one					381:383	one	381:383	one	381:383	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	3	16	theme	N-linked	407:414	arg1	glycosylation					417:429	asparagine-linked (N-linked) glycosylation	388:429	asparagine-linked (N-linked) glycosylation	388:429	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	1	17	theme	T-type	108:113	arg1	channels					115:122	T-type channels	108:122	T-type channels	108:122	T-type channels are low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity.
30600443	1	17	theme	T-type	108:113	arg1	channels					150:157	low-voltage-activated channels	128:157	low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity	128:239	T-type channels are low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity.
30600443	5	18	theme	CaV3.1-T-type	645:657	arg1	current					672:678	CaV3.1-T-type Ca2+ channel current	645:678	CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa	645:690	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	1	19	theme	pacemaker	222:230	arg1	activity					232:239	pacemaker activity	222:239	pacemaker activity	222:239	T-type channels are low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity.
30600443	0	20	theme	Asparagine-linked	0:16	arg1	glycosylation					18:30	Asparagine-linked glycosylation	0:30	Asparagine-linked glycosylation	0:30	Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel.
30600443	5	21	theme	Ca2+	659:662	arg1	current					672:678	CaV3.1-T-type Ca2+ channel current	645:678	CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa	645:690	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	2	22	from	modifications	304:316	arg1	protein					321:327	protein	321:327	protein	321:327	Glycosylation is one of the most prevalent post-translational modifications in protein.
30600443	0	23	theme	voltage-dependent	41:57	arg1	properties					66:75	voltage-dependent gating properties	41:75	voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel	41:105	Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel.
30600443	11	24	theme	glycosidase	1046:1056	arg1	F					1065:1065	a glycosidase PNGase F	1044:1065	a glycosidase PNGase F	1044:1065	T was insensitive to a glycosidase PNGase F when the channels were expressed on the plasma membrane.
30600443	3	25	theme	various	336:342	arg1	types					358:362	various glycosylation types	336:362	various glycosylation types	336:362	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	5	26	theme	channel	664:670	arg1	current					672:678	CaV3.1-T-type Ca2+ channel current	645:678	CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa	645:690	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	1	27	theme	low-voltage-activated	128:148	arg1	channels					115:122	T-type channels	108:122	T-type channels	108:122	T-type channels are low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity.
30600443	1	27	theme	low-voltage-activated	128:148	arg1	channels					150:157	low-voltage-activated channels	128:157	low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity	128:239	T-type channels are low-voltage-activated channels that play a role in the cardiovascular system particularly for pacemaker activity.
30600443	5	28	theme	current	672:678	arg1	reduction					632:640	a reduction	630:640	a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa	630:690	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	5	29	link	N-linked	568:575	arg1	tunicamycin					611:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	3	30	theme	glycosylation	344:356	arg1	types					358:362	various glycosylation types	336:362	various glycosylation types	336:362	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	4	31	theme	glycosylation	493:505	arg1	roles					475:479	the roles	471:479	the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel	471:565	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
30600443	3	32	link	asparagine-linked	388:404	arg1	one					381:383	one	381:383	one	381:383	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	3	32	link	asparagine-linked	388:404	arg1	glycosylation					417:429	asparagine-linked (N-linked) glycosylation	388:429	asparagine-linked (N-linked) glycosylation	388:429	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	4	33	theme	N-linked	484:491	arg1	glycosylation					493:505	N-linked glycosylation	484:505	N-linked glycosylation	484:505	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
30600443	2	34	theme	prevalent	275:283	arg1	modifications					304:316	the most prevalent post-translational modifications	266:316	the most prevalent post-translational modifications in protein	266:327	Glycosylation is one of the most prevalent post-translational modifications in protein.
30600443	12	35	theme	surface	1201:1207	arg1	expression					1209:1218	the cell surface expression	1192:1218	the cell surface expression of the CaV3.1-T-type Ca2+ channel	1192:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	0	36	theme	gating	59:64	arg1	properties					66:75	voltage-dependent gating properties	41:75	voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel	41:105	Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel.
30600443	7	37	theme	inactivation	849:860	arg1	unaffected					872:881	unaffected	872:881	unaffected	872:881	Tunicamycin (24 h) significantly shifted the activation curve to the depolarization potentials, whereas the steady-state inactivation curve was unaffected.
30600443	7	37	theme	inactivation	849:860	arg1	curve					862:866	the steady-state inactivation curve	832:866	the steady-state inactivation curve	832:866	Tunicamycin (24 h) significantly shifted the activation curve to the depolarization potentials, whereas the steady-state inactivation curve was unaffected.
30600443	12	38	gly	N-glycosylation	1152:1166	arg1	cell					1196:1199	the cell surface expression	1192:1218	the cell surface expression of the CaV3.1-T-type Ca2+ channel	1192:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	12	38	gly	N-glycosylation	1152:1166	arg1	surface					1201:1207	the cell surface expression	1192:1218	the cell surface expression of the CaV3.1-T-type Ca2+ channel	1192:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	12	38	gly	N-glycosylation	1152:1166	arg1	channel					1246:1252	the CaV3.1-T-type Ca2+ channel	1223:1252	the CaV3.1-T-type Ca2+ channel	1223:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	12	38	gly	N-glycosylation	1152:1166	arg1	properties					1290:1299	the gating properties	1279:1299	the gating properties of the channel	1279:1314	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	12	39	theme	CaV3.1-T-type	1227:1239	arg1	channel					1246:1252	the CaV3.1-T-type Ca2+ channel	1223:1252	the CaV3.1-T-type Ca2+ channel	1223:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	0	40	theme	CaV3.1-T-type	80:92	arg1	channel					99:105	CaV3.1-T-type Ca2+ channel	80:105	CaV3.1-T-type Ca2+ channel	80:105	Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel.
30600443	0	41	theme	Ca2+	94:97	arg1	channel					99:105	CaV3.1-T-type Ca2+ channel	80:105	CaV3.1-T-type Ca2+ channel	80:105	Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel.
30600443	12	42	theme	cell	1196:1199	arg1	expression					1209:1218	the cell surface expression	1192:1218	the cell surface expression of the CaV3.1-T-type Ca2+ channel	1192:1252	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	11	43	theme	PNGase	1058:1063	arg1	F					1065:1065	a glycosidase PNGase F	1044:1065	a glycosidase PNGase F	1044:1065	T was insensitive to a glycosidase PNGase F when the channels were expressed on the plasma membrane.
30600443	6	44	dep	applied	700:706	arg1	T					692:692	T	692:692	T	692:692	T) when applied for 12 h or longer.
30600443	12	45	theme	channel	1308:1314	arg1	properties					1290:1299	the gating properties	1279:1299	the gating properties of the channel	1279:1314	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	8	46	theme	Use-dependent	884:896	arg1	inactivation					898:909	Use-dependent inactivation	884:909	Use-dependent inactivation of CaV3.1-ICa.	884:924	Use-dependent inactivation of CaV3.1-ICa.
30600443	7	47	theme	steady-state	836:847	arg1	unaffected					872:881	unaffected	872:881	unaffected	872:881	Tunicamycin (24 h) significantly shifted the activation curve to the depolarization potentials, whereas the steady-state inactivation curve was unaffected.
30600443	7	47	theme	steady-state	836:847	arg1	curve					862:866	the steady-state inactivation curve	832:866	the steady-state inactivation curve	832:866	Tunicamycin (24 h) significantly shifted the activation curve to the depolarization potentials, whereas the steady-state inactivation curve was unaffected.
30600443	12	48	theme	channel	1325:1331	arg1	proteins					1333:1340	the channel proteins	1321:1340	the channel proteins	1321:1340	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	5	49	theme	N-linked	568:575	arg1	tunicamycin					611:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	5	50	dep	current	672:678	arg1	CaV3.1-ICa					681:690	CaV3.1-ICa	681:690	CaV3.1-ICa	681:690	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	0	51	theme	channel	99:105	arg1	properties					66:75	voltage-dependent gating properties	41:75	voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel	41:105	Asparagine-linked glycosylation modifies voltage-dependent gating properties of CaV3.1-T-type Ca2+ channel.
30600443	2	52	theme	modifications	304:316	arg1	modifications					304:316	the most prevalent post-translational modifications	266:316	the most prevalent post-translational modifications in protein	266:327	Glycosylation is one of the most prevalent post-translational modifications in protein.
30600443	2	52	theme	modifications	304:316	arg1	one					259:261	one	259:261	one	259:261	Glycosylation is one of the most prevalent post-translational modifications in protein.
30600443	5	53	theme	glycosylation	577:589	arg1	tunicamycin					611:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	12	54	theme	properties	1290:1299	arg1	regulation					1265:1274	the regulation	1261:1274	the regulation of the gating properties of the channel	1261:1314	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	8	55	theme	CaV3.1-ICa	914:923	arg1	inactivation					898:909	Use-dependent inactivation	884:909	Use-dependent inactivation of CaV3.1-ICa.	884:924	Use-dependent inactivation of CaV3.1-ICa.
30600443	7	56	theme	depolarization	797:810	arg1	potentials					812:821	the depolarization potentials	793:821	the depolarization potentials	793:821	Tunicamycin (24 h) significantly shifted the activation curve to the depolarization potentials, whereas the steady-state inactivation curve was unaffected.
30600443	3	57	theme	asparagine-linked	388:404	arg1	one					381:383	one	381:383	one	381:383	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	3	57	theme	asparagine-linked	388:404	arg1	glycosylation					417:429	asparagine-linked (N-linked) glycosylation	388:429	asparagine-linked (N-linked) glycosylation	388:429	Among various glycosylation types, the most common one is asparagine-linked (N-linked) glycosylation.
30600443	4	58	theme	Ca2+	554:557	arg1	channel					559:565	the CaV3.1-T-type Ca2+ channel	536:565	the CaV3.1-T-type Ca2+ channel	536:565	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
30600443	2	59	theme	post-translational	285:302	arg1	modifications					304:316	the most prevalent post-translational modifications	266:316	the most prevalent post-translational modifications in protein	266:327	Glycosylation is one of the most prevalent post-translational modifications in protein.
30600443	5	60	theme	synthesis	591:599	arg1	tunicamycin					611:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin	568:621	N-linked glycosylation synthesis inhibitor tunicamycin causes a reduction of CaV3.1-T-type Ca2+ channel current (CaV3.1-ICa.
30600443	12	61	theme	gating	1283:1288	arg1	properties					1290:1299	the gating properties	1279:1299	the gating properties of the channel	1279:1314	These findings suggest that N-glycosylation contributes not only to the cell surface expression of the CaV3.1-T-type Ca2+ channel but to the regulation of the gating properties of the channel when the channel proteins were processed during the folding and trafficking steps in the cell.
30600443	4	62	link	N-linked	484:491	arg1	glycosylation					493:505	N-linked glycosylation	484:505	N-linked glycosylation	484:505	The aim of this study was to elucidate the roles of N-linked glycosylation for the gating properties of the CaV3.1-T-type Ca2+ channel.
31667130	14	0	theme	abstracting	2284:2294	arg1	services					2307:2314	electronic abstracting & indexing services	2273:2314	electronic abstracting & indexing services	2273:2314	•Remember that the abstract is what readers see first in electronic abstracting & indexing services.
31667130	10	1	theme	leukemia	1696:1703	arg1	cell					1705:1708	a leukemia cell	1694:1708	a leukemia cell (L1210)	1694:1716	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	1	theme	leukemia	1696:1703	arg1	L1210					1711:1715	L1210	1711:1715	L1210	1711:1715	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	11	2	theme	safety	1939:1944	arg1	profiles					1946:1953	safety profiles	1939:1953	safety profiles	1939:1953	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	17	3	theme	accurate	2411:2418	arg1	•Be					2407:2409	•Be	2407:2409	•Be	2407:2409	•Be accurate and specific, keep it as brief as possible.
31667130	3	4	theme	processes	535:543	arg1	synthesis					503:511	the synthesis	499:511	the synthesis of specific branching processes in cancer cells, killing tumor cells	499:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	4	5	theme	committed	689:697	arg1	enzyme					699:704	the first committed enzyme	679:704	the first committed enzyme	679:704	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	4	5	theme	committed	689:697	arg1	N-acetylglucosaminephosphotransferase					726:762	dolichyl-phosphate N-acetylglucosaminephosphotransferase 1	707:764	dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1)	707:773	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	10	6	theme	low	1640:1642	arg1	concentrations					1647:1660	low μM concentrations	1640:1660	low μM concentrations	1640:1660	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	8	7	theme	hemolytic	1293:1301	arg1	activity					1303:1310	the hemolytic activity	1289:1310	the hemolytic activity of APPB	1289:1318	A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC50 > 200 μM RBC).
31667130	3	8	theme	specific	516:523	arg1	processes					535:543	specific branching processes	516:543	specific branching processes in cancer cells, killing tumor cells	516:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	5	9	theme	increased	884:892	arg1	branching					894:902	increased branching	884:902	increased branching of N-linked glycans in their growth progressions	884:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	1	10	theme	N-linked	244:251	arg1	glycans					253:259	N-linked glycans	244:259	N-linked glycans	244:259	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	13	11	theme	physicochemical	2163:2177	arg1	data					2179:2182	its physicochemical data	2159:2182	its physicochemical data	2159:2182	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	6	12	theme	difficile	1003:1011	arg1	APPB					1070:1073	APPB	1070:1073	APPB	1070:1073	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	6	12	theme	difficile	1003:1011	arg1	butanamide					1058:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	6	12	theme	difficile	1003:1011	arg1	molecule					1013:1020	an anti-Clostridium difficile molecule	983:1020	an anti-Clostridium difficile molecule	983:1020	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	0	13	theme	in	108:109	arg1	studies					116:122	in vivo studies	108:122	in vivo studies	108:122	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	3	14	theme	cancer	548:553	arg1	cells					576:580	killing tumor cells	562:580	killing tumor cells	562:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	3	14	theme	cancer	548:553	arg1	cells					555:559	cancer cells	548:559	cancer cells	548:559	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	5	15	theme	solid	857:861	arg1	cancers					863:869	certain solid cancers	849:869	certain solid cancers that require increased branching of N-linked glycans in their growth progressions	849:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	10	16	dep	cells	1734:1738	arg1	HPNE					1750:1753	HPNE	1750:1753	HPNE	1750:1753	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	16	dep	cells	1734:1738	arg1	Vero					1741:1744	Vero	1741:1744	Vero	1741:1744	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	16	dep	cells	1734:1738	arg1	cells					1734:1738	the healthy cells	1722:1738	the healthy cells (Vero and HPNE)	1722:1754	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	4	17	theme	N-glycan	623:630	arg1	biosynthesis					632:643	N-glycan biosynthesis	623:643	N-glycan biosynthesis	623:643	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	11	18	theme	In	1781:1782	arg1	stability					1800:1808	In vitro metabolic stability	1781:1808	In vitro metabolic stability using rat liver microsomes	1781:1835	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	1	19	from	due	196:198	arg1	part					209:212	large part	203:212	large part	203:212	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	11	20	dep	in	1915:1916	arg1	vivo					1918:1921	vivo	1918:1921	vivo	1918:1921	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	21	theme	animal	1984:1989	arg1	models					1991:1996	animal models	1984:1996	animal models	1984:1996	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	13	22	theme	gram-scale	2126:2135	arg1	synthesis					2137:2145	gram-scale synthesis	2126:2145	gram-scale synthesis of APPB	2126:2153	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	8	23	theme	IC50 > 200 μM	1349:1361	arg1	RBC					1363:1365	IC50 > 200 μM RBC	1349:1365	IC50 > 200 μM RBC	1349:1365	A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC50 > 200 μM RBC).
31667130	3	24	theme	tumor	570:574	arg1	cells					576:580	killing tumor cells	562:580	killing tumor cells	562:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	3	24	theme	tumor	570:574	arg1	cells					555:559	cancer cells	548:559	cancer cells	548:559	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	11	25	dep	studies	1923:1929	arg1	PK/PD					1932:1936	PK/PD	1932:1936	PK/PD	1932:1936	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	25	dep	studies	1923:1929	arg1	efficacy					1968:1975	in vivo efficacy	1960:1975	in vivo efficacy	1960:1975	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	25	dep	studies	1923:1929	arg1	profiles					1946:1953	safety profiles	1939:1953	safety profiles	1939:1953	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	25	dep	studies	1923:1929	arg1	studies					1923:1929	in vivo studies	1915:1929	in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models	1915:1996	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	5	26	contain	have	804:807	arg2	potential					835:843	the promising therapeutic potential	809:843	the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions	809:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	5	26	contain	have	804:807	arg1	inhibitors					793:802	Selective DPAGT1 inhibitors	776:802	Selective DPAGT1 inhibitors	776:802	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	1	27	from	part	209:212	arg1	due					196:198	due	196:198	due	196:198	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	10	28	theme	healthy	1726:1732	arg1	HPNE					1750:1753	HPNE	1750:1753	HPNE	1750:1753	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	28	theme	healthy	1726:1732	arg1	Vero					1741:1744	Vero	1741:1744	Vero	1741:1744	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	28	theme	healthy	1726:1732	arg1	cells					1734:1738	the healthy cells	1722:1738	the healthy cells (Vero and HPNE)	1722:1754	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	5	29	from	branching	894:902	arg1	progressions					940:951	their growth progressions	927:951	their growth progressions	927:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	5	30	theme	glycans	916:922	arg1	branching					894:902	increased branching	884:902	increased branching of N-linked glycans in their growth progressions	884:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	10	31	theme	novel	1494:1498	arg1	inhibitor					1507:1515	A novel DPAGT1 inhibitor	1492:1515	A novel DPAGT1 inhibitor	1492:1515	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	31	theme	novel	1494:1498	arg1	APPB					1518:1521	APPB	1518:1521	APPB	1518:1521	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	0	32	theme	phenoxypiperidinbenzyl	63:84	arg1	APPB					98:101	APPB	98:101	APPB	98:101	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	0	32	theme	phenoxypiperidinbenzyl	63:84	arg1	butanamide					86:95	aminouridyl phenoxypiperidinbenzyl butanamide	51:95	aminouridyl phenoxypiperidinbenzyl butanamide (APPB)	51:102	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	0	32	theme	phenoxypiperidinbenzyl	63:84	arg1	inhibitor					40:48	a novel DPAGT1 inhibitor	25:48	a novel DPAGT1 inhibitor	25:48	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	1	33	theme	N-linked	152:159	arg1	glycans					161:167	N-linked glycans	152:167	N-linked glycans	152:167	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	6	34	theme	phenoxypiperidinbenzyl	1035:1056	arg1	butanamide					1058:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	6	34	theme	phenoxypiperidinbenzyl	1035:1056	arg1	molecule					1013:1020	an anti-Clostridium difficile molecule	983:1020	an anti-Clostridium difficile molecule	983:1020	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	11	35	theme	in	1915:1916	arg1	efficacy					1968:1975	in vivo efficacy	1960:1975	in vivo efficacy	1960:1975	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	35	theme	in	1915:1916	arg1	PK/PD					1932:1936	PK/PD	1932:1936	PK/PD	1932:1936	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	35	theme	in	1915:1916	arg1	studies					1923:1929	in vivo studies	1915:1929	in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models	1915:1996	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	17	36	theme	specific	2424:2431	arg1	•Be					2407:2409	•Be	2407:2409	•Be	2407:2409	•Be accurate and specific, keep it as brief as possible.
31667130	3	37	from	processes	535:543	arg1	cells					576:580	killing tumor cells	562:580	killing tumor cells	562:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	3	37	from	processes	535:543	arg1	cells					555:559	cancer cells	548:559	cancer cells	548:559	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	15	38	theme	article	2351:2357	arg1	•This					2316:2320	•This	2316:2320	•This	2316:2320	•This is the advertisement of your article.
31667130	15	38	theme	article	2351:2357	arg1	advertisement					2329:2341	the advertisement	2325:2341	the advertisement of your article	2325:2357	•This is the advertisement of your article.
31667130	12	39	from	steps	2019:2023	arg1	synthesis					2052:2060	the previously reported synthesis	2028:2060	the previously reported synthesis for APPB for larger-scale	2028:2086	We have refined all steps in the previously reported synthesis for APPB for larger-scale.
31667130	9	40	dep	tunicamycin	1429:1439	arg1	<0.2 mg/mL					1463:1472	<0.2 mg/mL	1463:1472	<0.2 mg/mL for tunicamycin	1463:1488	Water solubility of APPB is >350-times greater than that of tunicamycin (78.8 mg/mL for APPB, <0.2 mg/mL for tunicamycin).
31667130	9	40	dep	tunicamycin	1429:1439	arg1	78.8 mg/mL					1442:1451	78.8 mg/mL	1442:1451	78.8 mg/mL for APPB	1442:1460	Water solubility of APPB is >350-times greater than that of tunicamycin (78.8 mg/mL for APPB, <0.2 mg/mL for tunicamycin).
31667130	11	41	theme	APPB	1875:1878	arg1	long					1896:1899	long	1896:1899	long	1896:1899	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	41	theme	APPB	1875:1878	arg1	t					1865:1865	t 1/2	1865:1869	t 1/2	1865:1869	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	41	theme	APPB	1875:1878	arg1	half-life					1854:1862	a half-life	1852:1862	a half-life (t 1/2) of APPB	1852:1878	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	41	theme	APPB	1875:1878	arg1	>60 min					1902:1908	>60 min	1902:1908	>60 min	1902:1908	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	42	dep	In	1781:1782	arg1	vitro					1784:1788	vitro	1784:1788	vitro	1784:1788	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	5	43	theme	DPAGT1	786:791	arg1	inhibitors					793:802	Selective DPAGT1 inhibitors	776:802	Selective DPAGT1 inhibitors	776:802	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	2	44	theme	glycosyl	357:364	arg1	transferases					366:377	glycosyl transferases	357:377	glycosyl transferases	357:377	N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus.
31667130	5	45	theme	therapeutic	823:833	arg1	potential					835:843	the promising therapeutic potential	809:843	the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions	809:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	9	46	theme	APPB	1389:1392	arg1	solubility					1375:1384	Water solubility	1369:1384	Water solubility of APPB	1369:1392	Water solubility of APPB is >350-times greater than that of tunicamycin (78.8 mg/mL for APPB, <0.2 mg/mL for tunicamycin).
31667130	13	47	theme	synthesis	2137:2145	arg1	assay					2209:2213	a convenient DPAGT1 assay	2189:2213	a convenient DPAGT1 assay	2189:2213	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	13	47	theme	synthesis	2137:2145	arg1	protocols					2113:2121	protocols	2113:2121	protocols of gram-scale synthesis of APPB	2113:2153	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	13	47	theme	synthesis	2137:2145	arg1	data					2179:2182	its physicochemical data	2159:2182	its physicochemical data	2159:2182	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	13	48	theme	APPB	2150:2153	arg1	synthesis					2137:2145	gram-scale synthesis	2126:2145	gram-scale synthesis of APPB	2126:2153	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	2	49	theme	Golgi	386:390	arg1	apparatus					392:400	the Golgi apparatus	382:400	the Golgi apparatus	382:400	N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus.
31667130	6	50	theme	DPAGT1	1083:1088	arg1	activity					1101:1108	DPAGT1 inhibitory activity	1083:1108	DPAGT1 inhibitory activity	1083:1108	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	3	51	theme	glycosyl	466:473	arg1	transferases					475:486	glycosyl transferases	466:486	glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively	466:592	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	0	52	theme	DPAGT1	33:38	arg1	butanamide					86:95	aminouridyl phenoxypiperidinbenzyl butanamide	51:95	aminouridyl phenoxypiperidinbenzyl butanamide (APPB)	51:102	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	0	52	theme	DPAGT1	33:38	arg1	inhibitor					40:48	a novel DPAGT1 inhibitor	25:48	a novel DPAGT1 inhibitor	25:48	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	10	53	theme	solid	1558:1562	arg1	Panc-1					1617:1622	Panc-1	1617:1622	Panc-1	1617:1622	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	53	theme	solid	1558:1562	arg1	tumors					1564:1569	the solid tumors	1554:1569	the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1)	1554:1635	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	53	theme	solid	1558:1562	arg1	SK-OV-3					1587:1593	SK-OV-3	1587:1593	SK-OV-3	1587:1593	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	53	theme	solid	1558:1562	arg1	MDA-MB-432S					1596:1606	MDA-MB-432S	1596:1606	MDA-MB-432S	1596:1606	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	53	theme	solid	1558:1562	arg1	AsPC-1					1629:1634	AsPC-1	1629:1634	AsPC-1	1629:1634	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	53	theme	solid	1558:1562	arg1	KB					1577:1578	KB	1577:1578	KB	1577:1578	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	53	theme	solid	1558:1562	arg1	LoVo					1581:1584	LoVo	1581:1584	LoVo	1581:1584	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	53	theme	solid	1558:1562	arg1	HCT116					1609:1614	HCT116	1609:1614	HCT116	1609:1614	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	11	54	theme	liver	1820:1824	arg1	microsomes					1826:1835	rat liver microsomes	1816:1835	rat liver microsomes	1816:1835	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	55	theme	metabolic	1790:1798	arg1	stability					1800:1808	In vitro metabolic stability	1781:1808	In vitro metabolic stability using rat liver microsomes	1781:1835	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	1	56	theme	large	203:207	arg1	part					209:212	large part	203:212	large part	203:212	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	14	57	theme	&	2296:2296	arg1	services					2307:2314	electronic abstracting & indexing services	2273:2314	electronic abstracting & indexing services	2273:2314	•Remember that the abstract is what readers see first in electronic abstracting & indexing services.
31667130	10	58	theme	cell	1705:1708	arg1	growth					1684:1689	growth	1684:1689	growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE)	1684:1754	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	6	59	theme	0.25 μM	1133:1139	arg1	value					1124:1128	the IC50 value	1115:1128	the IC50 value of 0.25 μM	1115:1139	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	10	60	dep	tumors	1564:1569	arg1	Panc-1					1617:1622	Panc-1	1617:1622	Panc-1	1617:1622	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	60	dep	tumors	1564:1569	arg1	tumors					1564:1569	the solid tumors	1554:1569	the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1)	1554:1635	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	60	dep	tumors	1564:1569	arg1	SK-OV-3					1587:1593	SK-OV-3	1587:1593	SK-OV-3	1587:1593	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	60	dep	tumors	1564:1569	arg1	MDA-MB-432S					1596:1606	MDA-MB-432S	1596:1606	MDA-MB-432S	1596:1606	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	60	dep	tumors	1564:1569	arg1	AsPC-1					1629:1634	AsPC-1	1629:1634	AsPC-1	1629:1634	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	60	dep	tumors	1564:1569	arg1	KB					1577:1578	KB	1577:1578	KB	1577:1578	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	60	dep	tumors	1564:1569	arg1	LoVo					1581:1584	LoVo	1581:1584	LoVo	1581:1584	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	60	dep	tumors	1564:1569	arg1	HCT116					1609:1614	HCT116	1609:1614	HCT116	1609:1614	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	14	61	theme	electronic	2273:2282	arg1	services					2307:2314	electronic abstracting & indexing services	2273:2314	electronic abstracting & indexing services	2273:2314	•Remember that the abstract is what readers see first in electronic abstracting & indexing services.
31667130	3	62	theme	branching	525:533	arg1	processes					535:543	specific branching processes	516:543	specific branching processes in cancer cells, killing tumor cells	516:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	1	63	theme	specificity	229:239	arg1	lack					221:224	the lack	217:224	the lack of specificity of N-linked glycans between normal and malignant cells	217:294	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	3	64	from	synthesis	503:511	arg1	cells					576:580	killing tumor cells	562:580	killing tumor cells	562:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	3	64	from	synthesis	503:511	arg1	cells					555:559	cancer cells	548:559	cancer cells	548:559	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	5	65	theme	Selective	776:784	arg1	inhibitors					793:802	Selective DPAGT1 inhibitors	776:802	Selective DPAGT1 inhibitors	776:802	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	11	66	dep	long	1896:1899	arg1	long					1896:1899	long	1896:1899	long	1896:1899	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	66	dep	long	1896:1899	arg1	half-life					1854:1862	a half-life	1852:1862	a half-life (t 1/2) of APPB	1852:1878	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	66	dep	long	1896:1899	arg1	>60 min					1902:1908	>60 min	1902:1908	>60 min	1902:1908	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	8	67	theme	sharp	1234:1238	arg1	difference					1240:1249	A sharp difference	1232:1249	A sharp difference between APPB and tunicamycin	1232:1278	A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC50 > 200 μM RBC).
31667130	2	68	from	action	347:352	arg1	apparatus					392:400	the Golgi apparatus	382:400	the Golgi apparatus	382:400	N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus.
31667130	5	69	theme	certain	849:855	arg1	cancers					863:869	certain solid cancers	849:869	certain solid cancers that require increased branching of N-linked glycans in their growth progressions	849:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	6	70	theme	anti-Clostridium	986:1001	arg1	APPB					1070:1073	APPB	1070:1073	APPB	1070:1073	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	6	70	theme	anti-Clostridium	986:1001	arg1	butanamide					1058:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	6	70	theme	anti-Clostridium	986:1001	arg1	molecule					1013:1020	an anti-Clostridium difficile molecule	983:1020	an anti-Clostridium difficile molecule	983:1020	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	0	71	dep	in	108:109	arg1	vivo					111:114	vivo	111:114	vivo	111:114	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	8	72	theme	APPB	1315:1318	arg1	activity					1303:1310	the hemolytic activity	1289:1310	the hemolytic activity of APPB	1289:1318	A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC50 > 200 μM RBC).
31667130	11	73	theme	rat	1816:1818	arg1	microsomes					1826:1835	rat liver microsomes	1816:1835	rat liver microsomes	1816:1835	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	74	theme	in	1960:1961	arg1	efficacy					1968:1975	in vivo efficacy	1960:1975	in vivo efficacy	1960:1975	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	11	74	theme	in	1960:1961	arg1	studies					1923:1929	in vivo studies	1915:1929	in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models	1915:1996	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	10	75	dep	KB	1577:1578	arg1	e.g.					1572:1575	e.g.	1572:1575	e.g.	1572:1575	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	3	76	theme	killing	562:568	arg1	cells					576:580	killing tumor cells	562:580	killing tumor cells	562:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	3	76	theme	killing	562:568	arg1	cells					555:559	cancer cells	548:559	cancer cells	548:559	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	5	77	theme	growth	933:938	arg1	progressions					940:951	their growth progressions	927:951	their growth progressions	927:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	4	78	theme	first	683:687	arg1	enzyme					699:704	the first committed enzyme	679:704	the first committed enzyme	679:704	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	4	78	theme	first	683:687	arg1	N-acetylglucosaminephosphotransferase					726:762	dolichyl-phosphate N-acetylglucosaminephosphotransferase 1	707:764	dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1)	707:773	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	12	79	theme	reported	2043:2050	arg1	synthesis					2052:2060	the previously reported synthesis	2028:2060	the previously reported synthesis for APPB for larger-scale	2028:2086	We have refined all steps in the previously reported synthesis for APPB for larger-scale.
31667130	0	80	theme	novel	27:31	arg1	butanamide					86:95	aminouridyl phenoxypiperidinbenzyl butanamide	51:95	aminouridyl phenoxypiperidinbenzyl butanamide (APPB)	51:102	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	0	80	theme	novel	27:31	arg1	inhibitor					40:48	a novel DPAGT1 inhibitor	25:48	a novel DPAGT1 inhibitor	25:48	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	4	81	theme	enzyme	699:704	arg1	disruption					665:674	disruption	665:674	disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1)	665:773	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	3	82	from	cells	555:559	arg1	synthesis					503:511	the synthesis	499:511	the synthesis of specific branching processes in cancer cells, killing tumor cells	499:580	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	3	83	theme	overwhelming	412:423	arg1	It					403:404	It	403:404	It	403:404	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	3	83	theme	overwhelming	412:423	arg1	task					425:428	an overwhelming task	409:428	an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively	409:592	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	0	84	theme	aminouridyl	51:61	arg1	APPB					98:101	APPB	98:101	APPB	98:101	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	0	84	theme	aminouridyl	51:61	arg1	butanamide					86:95	aminouridyl phenoxypiperidinbenzyl butanamide	51:95	aminouridyl phenoxypiperidinbenzyl butanamide (APPB)	51:102	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	0	84	theme	aminouridyl	51:61	arg1	inhibitor					40:48	a novel DPAGT1 inhibitor	25:48	a novel DPAGT1 inhibitor	25:48	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	13	85	theme	convenient	2191:2200	arg1	assay					2209:2213	a convenient DPAGT1 assay	2189:2213	a convenient DPAGT1 assay	2189:2213	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	5	86	theme	N-linked	907:914	arg1	glycans					916:922	N-linked glycans	907:922	N-linked glycans	907:922	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	15	87	theme	your	2346:2349	arg1	article					2351:2357	your article	2346:2357	your article	2346:2357	•This is the advertisement of your article.
31667130	8	88	dep	attenuated	1337:1346	arg1	RBC					1363:1365	IC50 > 200 μM RBC	1349:1365	IC50 > 200 μM RBC	1349:1365	A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC50 > 200 μM RBC).
31667130	10	89	theme	cells	1734:1738	arg1	growth					1684:1689	growth	1684:1689	growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE)	1684:1754	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	6	90	theme	aminouridyl	1023:1033	arg1	butanamide					1058:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	aminouridyl phenoxypiperidinbenzyl butanamide	1023:1067	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	6	90	theme	aminouridyl	1023:1033	arg1	molecule					1013:1020	an anti-Clostridium difficile molecule	983:1020	an anti-Clostridium difficile molecule	983:1020	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	9	91	theme	Water	1369:1373	arg1	solubility					1375:1384	Water solubility	1369:1384	Water solubility of APPB	1369:1392	Water solubility of APPB is >350-times greater than that of tunicamycin (78.8 mg/mL for APPB, <0.2 mg/mL for tunicamycin).
31667130	13	92	theme	DPAGT1	2202:2207	arg1	assay					2209:2213	a convenient DPAGT1 assay	2189:2213	a convenient DPAGT1 assay	2189:2213	This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay.
31667130	10	93	theme	μM	1644:1645	arg1	concentrations					1647:1660	low μM concentrations	1640:1660	low μM concentrations	1640:1660	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	5	94	theme	promising	813:821	arg1	potential					835:843	the promising therapeutic potential	809:843	the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions	809:951	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	7	95	from	concentration	1217:1229	arg1	N-glycosylation					1178:1192	N-glycosylation	1178:1192	N-glycosylation of β-catenin at 2.5 nM concentration	1178:1229	It was confirmed that APPB inhibits N-glycosylation of β-catenin at 2.5 nM concentration.
31667130	6	96	theme	IC50	1119:1122	arg1	value					1124:1128	the IC50 value	1115:1128	the IC50 value of 0.25 μM	1115:1139	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	10	97	theme	DPAGT1	1500:1505	arg1	inhibitor					1507:1515	A novel DPAGT1 inhibitor	1492:1515	A novel DPAGT1 inhibitor	1492:1515	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	10	97	theme	DPAGT1	1500:1505	arg1	APPB					1518:1521	APPB	1518:1521	APPB	1518:1521	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	4	98	theme	dolichyl-phosphate	707:724	arg1	enzyme					699:704	the first committed enzyme	679:704	the first committed enzyme	679:704	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	4	98	theme	dolichyl-phosphate	707:724	arg1	N-acetylglucosaminephosphotransferase					726:762	dolichyl-phosphate N-acetylglucosaminephosphotransferase 1	707:764	dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1)	707:773	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	4	98	theme	dolichyl-phosphate	707:724	arg1	DPAGT1					767:772	DPAGT1	767:772	DPAGT1	767:772	It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1).
31667130	7	99	theme	2.5 nM	1210:1215	arg1	concentration					1217:1229	2.5 nM concentration	1210:1229	2.5 nM concentration	1210:1229	It was confirmed that APPB inhibits N-glycosylation of β-catenin at 2.5 nM concentration.
31667130	1	100	theme	glycans	253:259	arg1	specificity					229:239	specificity	229:239	specificity of N-linked glycans between normal and malignant cells	229:294	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	1	101	link	N-linked	152:159	arg1	glycans					161:167	N-linked glycans	152:167	N-linked glycans	152:167	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	3	102	theme	drug-like	442:450	arg1	inhibitors					452:461	drug-like inhibitors	442:461	drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively	442:592	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	7	103	theme	β-catenin	1197:1205	arg1	N-glycosylation					1178:1192	N-glycosylation	1178:1192	N-glycosylation of β-catenin at 2.5 nM concentration	1178:1229	It was confirmed that APPB inhibits N-glycosylation of β-catenin at 2.5 nM concentration.
31667130	1	104	theme	normal	269:274	arg1	cells					290:294	normal and malignant cells	269:294	normal and malignant cells	269:294	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	5	105	link	N-linked	907:914	arg1	glycans					916:922	N-linked glycans	907:922	N-linked glycans	907:922	Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions.
31667130	6	106	theme	inhibitory	1090:1099	arg1	activity					1101:1108	DPAGT1 inhibitory activity	1083:1108	DPAGT1 inhibitory activity	1083:1108	Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM.
31667130	0	107	theme	inhibitor	40:48	arg1	synthesis					12:20	A practical synthesis	0:20	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.	0:123	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
31667130	1	108	theme	malignant	280:288	arg1	cells					290:294	normal and malignant cells	269:294	normal and malignant cells	269:294	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	2	109	theme	sequential	336:345	arg1	action					347:352	the sequential action	332:352	the sequential action of glycosyl transferases in the Golgi apparatus	332:400	N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus.
31667130	10	110	theme	tumors	1564:1569	arg1	growth					1544:1549	growth	1544:1549	growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1)	1544:1635	A novel DPAGT1 inhibitor, APPB selectively inhibits growth of the solid tumors (e.g. KB, LoVo, SK-OV-3, MDA-MB-432S, HCT116, Panc-1, and AsPC-1) at low μM concentrations, but does not inhibit growth of a leukemia cell (L1210) and the healthy cells (Vero and HPNE) at these concentrations.
31667130	7	111	gly	N-glycosylation	1178:1192	arg1	β-catenin					1197:1205	β-catenin	1197:1205	β-catenin	1197:1205	It was confirmed that APPB inhibits N-glycosylation of β-catenin at 2.5 nM concentration.
31667130	7	111	gly	N-glycosylation	1178:1192	arg1	concentration					1217:1229	2.5 nM concentration	1210:1229	2.5 nM concentration	1210:1229	It was confirmed that APPB inhibits N-glycosylation of β-catenin at 2.5 nM concentration.
31667130	7	111	gly	N-glycosylation	1178:1192	arg2	concentration					1217:1229	2.5 nM concentration	1210:1229	2.5 nM concentration	1210:1229	It was confirmed that APPB inhibits N-glycosylation of β-catenin at 2.5 nM concentration.
31667130	3	112	theme	transferases	475:486	arg1	inhibitors					452:461	drug-like inhibitors	442:461	drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively	442:592	It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively.
31667130	14	113	theme	indexing	2298:2305	arg1	services					2307:2314	electronic abstracting & indexing services	2273:2314	electronic abstracting & indexing services	2273:2314	•Remember that the abstract is what readers see first in electronic abstracting & indexing services.
31667130	2	114	theme	N-Glycan	297:304	arg1	chains					306:311	N-Glycan chains	297:311	N-Glycan chains	297:311	N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus.
31667130	2	115	theme	transferases	366:377	arg1	action					347:352	the sequential action	332:352	the sequential action of glycosyl transferases in the Golgi apparatus	332:400	N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus.
31667130	11	116	dep	in	1960:1961	arg1	vivo					1963:1966	vivo	1963:1966	vivo	1963:1966	In vitro metabolic stability using rat liver microsomes indicated that a half-life (t 1/2) of APPB is sufficiently long (>60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models.
31667130	1	117	link	N-linked	244:251	arg1	glycans					253:259	N-linked glycans	244:259	N-linked glycans	244:259	Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells.
31667130	0	118	theme	practical	2:10	arg1	synthesis					12:20	A practical synthesis	0:20	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.	0:123	A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies.
30982351	17	0	theme	quality	1667:1673	arg1	characteristics					1675:1689	quality characteristics	1667:1689	quality characteristics	1667:1689	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	5	1	theme	floor	607:611	arg1	pens					613:616	160 raised floor pens	596:616	160 raised floor pens	596:616	Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens.
30982351	13	2	theme	samples	1241:1247	arg1	AME					1201:1203	AME	1201:1203	AME	1201:1203	There were differences (P < 0.05) in AME and N-corrected AME (AMEn) of wheat samples.
30982351	13	2	theme	samples	1241:1247	arg1	AME					1221:1223	N-corrected AME	1209:1223	N-corrected AME	1209:1223	There were differences (P < 0.05) in AME and N-corrected AME (AMEn) of wheat samples.
30982351	13	2	theme	samples	1241:1247	arg1	AMEn					1226:1229	AMEn	1226:1229	AMEn	1226:1229	There were differences (P < 0.05) in AME and N-corrected AME (AMEn) of wheat samples.
30982351	7	3	theme	AME	794:796	arg1	determination					798:810	AME determination	794:810	AME determination	794:810	Excreta were quantitatively collected during the last 3 days for AME determination.
30982351	17	4	theme	weight	1476:1481	arg1	WG					1489:1490	WG	1489:1490	WG	1489:1490	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	4	theme	weight	1476:1481	arg1	gain					1483:1486	weight gain	1476:1486	weight gain (WG)	1476:1491	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	2	5	from	characteristics	176:190	arg1	performance					353:363	broiler growth performance	338:363	broiler growth performance	338:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	9	6	theme	energy	854:859	arg1	content					820:826	The content	816:826	The content of protein, ash and gross energy (GE)	816:864	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	2	7	theme	samples	263:269	arg1	composition					155:165	chemical composition	146:165	chemical composition	146:165	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	7	theme	samples	263:269	arg1	energy					216:221	apparent metabolisable energy	193:221	apparent metabolisable energy (AME)	193:227	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	7	theme	samples	263:269	arg1	effect					328:333	their effect	322:333	their effect on broiler growth performance	322:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	7	theme	samples	263:269	arg1	AME					224:226	AME	224:226	AME	224:226	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	7	theme	samples	263:269	arg1	characteristics					176:190	quality characteristics	168:190	quality characteristics	168:190	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	7	theme	samples	263:269	arg1	nutrient					233:240	nutrient	233:240	nutrient	233:240	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	4	8	theme	UK	387:388	arg1	samples					396:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	2	9	theme	study	125:129	arg1	aim					113:115	The aim	109:115	The aim of this study	109:129	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	6	10	theme	block	715:719	arg1	design					721:726	a randomised complete block design	693:726	a randomised complete block design	693:726	Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design.
30982351	7	11	theme	last	778:781	arg1	days					785:788	the last 3 days	774:788	the last 3 days for AME determination	774:810	Excreta were quantitatively collected during the last 3 days for AME determination.
30982351	9	12	dep	18.24 MJ/kg	931:941	arg1	to					928:929	to	928:929	to	928:929	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	13	13	theme	N-corrected	1209:1219	arg1	AME					1221:1223	N-corrected AME	1209:1223	N-corrected AME	1209:1223	There were differences (P < 0.05) in AME and N-corrected AME (AMEn) of wheat samples.
30982351	6	14	theme	randomised	695:704	arg1	design					721:726	a randomised complete block design	693:726	a randomised complete block design	693:726	Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design.
30982351	20	15	theme	FD	1808:1809	arg1	r					1843:1843	r = 0.552	1843:1851	r = 0.552	1843:1851	The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05).
30982351	20	15	theme	FD	1808:1809	arg1	related					1826:1832	related	1826:1832	related	1826:1832	The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05).
30982351	20	15	theme	FD	1808:1809	arg1	coefficient					1793:1803	The coefficient	1789:1803	The coefficient of FD	1789:1809	The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05).
30982351	22	16	theme	wheat	1924:1928	arg1	characteristics					1901:1915	quality characteristics	1893:1915	quality characteristics	1893:1915	Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers.
30982351	22	16	theme	wheat	1924:1928	arg1	composition					1877:1887	Chemical composition	1868:1887	Chemical composition	1868:1887	Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers.
30982351	9	17	dep	19.6 g/kg	905:913	arg1	to					902:903	to	902:903	to	902:903	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	2	18	dep	energy	216:221	arg1	utilisation					242:252	utilisation	242:252	utilisation	242:252	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	19	theme	available	281:289	arg1	samples					263:269	wheat samples	257:269	wheat samples currently available to the UK poultry industry	257:316	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	15	20	dep	different	1398:1406	arg1	P					1409:1409	P < 0.05	1409:1416	P < 0.05	1409:1416	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	23	21	theme	samples	2069:2075	arg1	performance					2023:2033	growth performance	2016:2033	growth performance of broilers	2016:2045	There was no relationship between growth performance of broilers and AMEn of the wheat samples.
30982351	23	21	theme	samples	2069:2075	arg1	AMEn					2051:2054	AMEn	2051:2054	AMEn of the wheat samples	2051:2075	There was no relationship between growth performance of broilers and AMEn of the wheat samples.
30982351	22	22	theme	quality	1893:1899	arg1	characteristics					1901:1915	quality characteristics	1893:1915	quality characteristics	1893:1915	Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers.
30982351	2	23	theme	metabolisable	202:214	arg1	AME					224:226	AME	224:226	AME	224:226	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	23	theme	metabolisable	202:214	arg1	energy					216:221	apparent metabolisable energy	193:221	apparent metabolisable energy (AME)	193:227	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	23	24	theme	broilers	2038:2045	arg1	performance					2023:2033	growth performance	2016:2033	growth performance of broilers	2016:2045	There was no relationship between growth performance of broilers and AMEn of the wheat samples.
30982351	23	24	theme	broilers	2038:2045	arg1	AMEn					2051:2054	AMEn	2051:2054	AMEn of the wheat samples	2051:2075	There was no relationship between growth performance of broilers and AMEn of the wheat samples.
30982351	0	25	theme	metabolisable	57:69	arg1	value					78:82	the apparent metabolisable energy value	44:82	the apparent metabolisable energy value for broiler chickens	44:103	Wheat sample affects growth performance and the apparent metabolisable energy value for broiler chickens.
30982351	17	26	dep	significantly	1532:1544	arg1	P					1547:1547	P < 0.05	1547:1554	P < 0.05	1547:1554	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	19	27	dep	AMEn	1759:1762	arg1	r					1765:1765	r = - 0.489	1765:1775	r = - 0.489	1765:1775	The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05).
30982351	19	27	dep	AMEn	1759:1762	arg1	P					1778:1778	P < 0.05	1778:1785	P < 0.05	1778:1785	The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05).
30982351	5	28	theme	Ross	551:554	arg1	broilers					560:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens.
30982351	17	29	theme	daily	1449:1453	arg1	FI					1468:1469	FI	1468:1469	FI	1468:1469	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	29	theme	daily	1449:1453	arg1	intake					1460:1465	The daily feed intake	1445:1465	The daily feed intake (FI)	1445:1470	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	29	theme	daily	1449:1453	arg1	lower					1557:1561	lower	1557:1561	lower	1557:1561	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	11	30	theme	wheat	1119:1123	arg1	samples					1125:1131	wheat samples	1119:1131	wheat samples	1119:1131	The quality characteristics of wheat samples were in the expected range.
30982351	0	31	theme	broiler	88:94	arg1	chickens					96:103	broiler chickens	88:103	broiler chickens	88:103	Wheat sample affects growth performance and the apparent metabolisable energy value for broiler chickens.
30982351	10	32	theme	starch	975:980	arg1	amount					965:970	The amount	961:970	The amount of starch and total non-starch polysaccharides (NSP)	961:1023	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	32	theme	starch	975:980	arg1	NSP					1020:1022	NSP	1020:1022	NSP	1020:1022	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	32	theme	starch	975:980	arg1	polysaccharides					1003:1017	total non-starch polysaccharides	986:1017	total non-starch polysaccharides (NSP)	986:1023	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	32	theme	starch	975:980	arg1	starch					975:980	starch	975:980	starch	975:980	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	2	33	from	energy	216:221	arg1	performance					353:363	broiler growth performance	338:363	broiler growth performance	338:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	20	34	dep	related	1826:1832	arg1	r					1843:1843	r = 0.552	1843:1851	r = 0.552	1843:1851	The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05).
30982351	20	34	dep	related	1826:1832	arg1	P					1854:1854	P < 0.05	1854:1861	P < 0.05	1854:1861	The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05).
30982351	20	34	dep	related	1826:1832	arg1	related					1826:1832	related	1826:1832	related	1826:1832	The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05).
30982351	20	34	dep	related	1826:1832	arg1	coefficient					1793:1803	The coefficient	1789:1803	The coefficient of FD	1789:1809	The coefficient of FD was positively related to AMEn (r = 0.552, P < 0.05).
30982351	0	35	theme	Wheat	0:4	arg1	sample					6:11	Wheat sample	0:11	Wheat sample	0:11	Wheat sample affects growth performance and the apparent metabolisable energy value for broiler chickens.
30982351	10	36	theme	polysaccharides	1003:1017	arg1	amount					965:970	The amount	961:970	The amount of starch and total non-starch polysaccharides (NSP)	961:1023	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	36	theme	polysaccharides	1003:1017	arg1	NSP					1020:1022	NSP	1020:1022	NSP	1020:1022	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	36	theme	polysaccharides	1003:1017	arg1	polysaccharides					1003:1017	total non-starch polysaccharides	986:1017	total non-starch polysaccharides (NSP)	986:1023	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	36	theme	polysaccharides	1003:1017	arg1	starch					975:980	starch	975:980	starch	975:980	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	9	37	dep	143 g/kg	884:891	arg1	to					881:882	to	881:882	to	881:882	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	5	38	theme	1-day-old	536:544	arg1	broilers					560:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens.
30982351	14	39	theme	DM	1305:1306	arg1	range					1285:1289	a maximum range	1275:1289	a maximum range of 1.13 MJ/kg DM between samples	1275:1322	The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples.
30982351	10	40	theme	total	986:990	arg1	NSP					1020:1022	NSP	1020:1022	NSP	1020:1022	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	40	theme	total	986:990	arg1	polysaccharides					1003:1017	total non-starch polysaccharides	986:1017	total non-starch polysaccharides (NSP)	986:1023	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	4	41	theme	feed	516:519	arg1	330 g/kg					493:500	330 g/kg	493:500	330 g/kg of a balancer feed	493:519	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	4	41	theme	feed	516:519	arg1	670 g/kg					459:466	670 g/kg	459:466	670 g/kg of each wheat sample	459:487	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	6	42	theme	Each	619:622	arg1	diet					624:627	Each diet	619:627	Each diet	619:627	Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design.
30982351	10	43	dep	98.2 g/kg	1060:1068	arg1	to					1057:1058	to	1057:1058	to	1057:1058	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	4	44	theme	sample	482:487	arg1	330 g/kg					493:500	330 g/kg	493:500	330 g/kg of a balancer feed	493:519	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	4	44	theme	sample	482:487	arg1	670 g/kg					459:466	670 g/kg	459:466	670 g/kg of each wheat sample	459:487	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	15	45	theme	matter	1329:1334	arg1	DMR					1347:1349	DMR	1347:1349	DMR	1347:1349	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	15	45	theme	matter	1329:1334	arg1	retention					1336:1344	Dry matter retention	1325:1344	Dry matter retention (DMR)	1325:1350	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	22	46	theme	broilers	1972:1979	arg1	WG					1966:1967	WG	1966:1967	WG	1966:1967	Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers.
30982351	22	46	theme	broilers	1972:1979	arg1	FI					1959:1960	FI	1959:1960	FI	1959:1960	Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers.
30982351	2	47	theme	chemical	146:153	arg1	composition					155:165	chemical composition	146:165	chemical composition	146:165	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	14	48	theme	1.13 MJ/kg	1294:1303	arg1	DM					1305:1306	1.13 MJ/kg DM	1294:1306	1.13 MJ/kg DM	1294:1306	The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples.
30982351	10	49	dep	728	1044:1046	arg1	to					1041:1042	to	1041:1042	to	1041:1042	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	9	50	theme	protein	831:837	arg1	content					820:826	The content	816:826	The content of protein, ash and gross energy (GE)	816:864	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	2	51	theme	quality	168:174	arg1	characteristics					176:190	quality characteristics	168:190	quality characteristics	168:190	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	52	theme	growth	346:351	arg1	performance					353:363	broiler growth performance	338:363	broiler growth performance	338:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	22	53	dep	relate	1938:1943	arg1	P					1946:1946	P > 0.05	1946:1953	P > 0.05	1946:1953	Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers.
30982351	19	54	theme	= -	1767:1769	arg1	r					1765:1765	r = - 0.489	1765:1775	r = - 0.489	1765:1775	The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05).
30982351	19	54	theme	= -	1767:1769	arg1	P					1778:1778	P < 0.05	1778:1785	P < 0.05	1778:1785	The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05).
30982351	17	55	theme	wheat	1513:1517	arg1	samples					1519:1525	two wheat samples	1509:1525	two wheat samples	1509:1525	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	6	56	dep	21d	682:684	arg1	to					679:680	to	679:680	to	679:680	Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design.
30982351	9	57	theme	ash	840:842	arg1	content					820:826	The content	816:826	The content of protein, ash and gross energy (GE)	816:864	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	5	58	theme	raised	600:605	arg1	pens					613:616	160 raised floor pens	596:616	160 raised floor pens	596:616	Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens.
30982351	6	59	theme	ad	661:662	arg1	libitum					664:670	ad libitum	661:670	ad libitum	661:670	Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design.
30982351	13	60	theme	wheat	1235:1239	arg1	samples					1241:1247	wheat samples	1235:1247	wheat samples	1235:1247	There were differences (P < 0.05) in AME and N-corrected AME (AMEn) of wheat samples.
30982351	2	61	from	composition	155:165	arg1	performance					353:363	broiler growth performance	338:363	broiler growth performance	338:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	4	62	theme	current	379:385	arg1	samples					396:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	14	63	theme	wheat	1265:1269	arg1	AME					1254:1256	The AME	1250:1256	The AME of the wheat	1250:1269	The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples.
30982351	9	64	theme	gross	848:852	arg1	energy					854:859	gross energy	848:859	gross energy (GE)	848:864	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	9	64	theme	gross	848:852	arg1	GE					862:863	GE	862:863	GE	862:863	The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively.
30982351	2	65	from	effect	328:333	arg1	performance					353:363	broiler growth performance	338:363	broiler growth performance	338:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	4	66	theme	wheat	390:394	arg1	samples					396:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	15	67	theme	fat	1356:1358	arg1	FD					1375:1376	FD	1375:1376	FD	1375:1376	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	15	67	theme	fat	1356:1358	arg1	digestibility					1360:1372	fat digestibility	1356:1372	fat digestibility (FD)	1356:1377	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	2	68	theme	wheat	257:261	arg1	samples					263:269	wheat samples	257:269	wheat samples currently available to the UK poultry industry	257:316	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	6	69	theme	complete	706:713	arg1	block					715:719	complete block	706:719	a randomised complete block design	693:726	Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design.
30982351	2	70	theme	UK	298:299	arg1	industry					309:316	the UK poultry industry	294:316	the UK poultry industry	294:316	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	15	71	theme	wheat	1427:1431	arg1	samples					1433:1439	wheat samples	1427:1439	wheat samples	1427:1439	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	19	72	theme	wheat	1714:1718	arg1	samples					1720:1726	wheat samples	1714:1726	wheat samples	1714:1726	The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05).
30982351	14	73	contain	had	1271:1273	arg2	range					1285:1289	a maximum range	1275:1289	a maximum range of 1.13 MJ/kg DM between samples	1275:1322	The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples.
30982351	14	73	contain	had	1271:1273	arg1	AME					1254:1256	The AME	1250:1256	The AME of the wheat	1250:1269	The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples.
30982351	17	74	theme	chemical	1642:1649	arg1	composition					1651:1661	their chemical composition	1636:1661	their chemical composition	1636:1661	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	23	75	theme	wheat	2063:2067	arg1	samples					2069:2075	the wheat samples	2059:2075	the wheat samples	2059:2075	There was no relationship between growth performance of broilers and AMEn of the wheat samples.
30982351	0	76	theme	energy	71:76	arg1	value					78:82	the apparent metabolisable energy value	44:82	the apparent metabolisable energy value for broiler chickens	44:103	Wheat sample affects growth performance and the apparent metabolisable energy value for broiler chickens.
30982351	19	77	theme	ash	1699:1701	arg1	content					1703:1709	The ash content	1695:1709	The ash content of wheat samples	1695:1726	The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05).
30982351	4	78	theme	wheat	476:480	arg1	sample					482:487	each wheat sample	471:487	each wheat sample	471:487	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	4	79	used	used	409:412	arg2	samples					396:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples	369:402	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	17	80	theme	other	1578:1582	arg1	samples					1584:1590	other samples	1578:1590	other samples	1578:1590	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	5	81	theme	308	556:558	arg1	broilers					560:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens.
30982351	17	82	theme	feed	1455:1458	arg1	FI					1468:1469	FI	1468:1469	FI	1468:1469	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	82	theme	feed	1455:1458	arg1	intake					1460:1465	The daily feed intake	1445:1465	The daily feed intake (FI)	1445:1470	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	82	theme	feed	1455:1458	arg1	lower					1557:1561	lower	1557:1561	lower	1557:1561	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	11	83	theme	samples	1125:1131	arg1	characteristics					1100:1114	The quality characteristics	1088:1114	The quality characteristics of wheat samples	1088:1131	The quality characteristics of wheat samples were in the expected range.
30982351	23	84	theme	growth	2016:2021	arg1	performance					2023:2033	growth performance	2016:2033	growth performance of broilers	2016:2045	There was no relationship between growth performance of broilers and AMEn of the wheat samples.
30982351	19	85	theme	samples	1720:1726	arg1	content					1703:1709	The ash content	1695:1709	The ash content of wheat samples	1695:1726	The ash content of wheat samples was negatively associated with AMEn (r = - 0.489, P < 0.05).
30982351	17	86	theme	low	1602:1604	arg1	FI					1606:1607	their low FI	1596:1607	their low FI	1596:1607	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	4	87	theme	balancer	507:514	arg1	feed					516:519	a balancer feed	505:519	a balancer feed	505:519	Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed.
30982351	11	88	theme	expected	1145:1152	arg1	range					1154:1158	the expected range	1141:1158	the expected range	1141:1158	The quality characteristics of wheat samples were in the expected range.
30982351	0	89	theme	growth	21:26	arg1	performance					28:38	growth performance	21:38	growth performance	21:38	Wheat sample affects growth performance and the apparent metabolisable energy value for broiler chickens.
30982351	10	90	theme	non-starch	992:1001	arg1	NSP					1020:1022	NSP	1020:1022	NSP	1020:1022	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	10	90	theme	non-starch	992:1001	arg1	polysaccharides					1003:1017	total non-starch polysaccharides	986:1017	total non-starch polysaccharides (NSP)	986:1023	The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively.
30982351	5	91	theme	male	546:549	arg1	broilers					560:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers	522:567	Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens.
30982351	2	92	from	nutrient	233:240	arg1	performance					353:363	broiler growth performance	338:363	broiler growth performance	338:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	15	93	theme	Dry	1325:1327	arg1	DMR					1347:1349	DMR	1347:1349	DMR	1347:1349	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	15	93	theme	Dry	1325:1327	arg1	retention					1336:1344	Dry matter retention	1325:1344	Dry matter retention (DMR)	1325:1350	Dry matter retention (DMR) and fat digestibility (FD) were significantly different (P < 0.05) between wheat samples.
30982351	0	94	theme	apparent	48:55	arg1	value					78:82	the apparent metabolisable energy value	44:82	the apparent metabolisable energy value for broiler chickens	44:103	Wheat sample affects growth performance and the apparent metabolisable energy value for broiler chickens.
30982351	22	95	theme	Chemical	1868:1875	arg1	composition					1877:1887	Chemical composition	1868:1887	Chemical composition	1868:1887	Chemical composition and quality characteristics of the wheat did not relate (P > 0.05) to FI and WG of broilers.
30982351	2	96	theme	apparent	193:200	arg1	AME					224:226	AME	224:226	AME	224:226	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	2	96	theme	apparent	193:200	arg1	energy					216:221	apparent metabolisable energy	193:221	apparent metabolisable energy (AME)	193:227	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	17	97	theme	broilers	1496:1503	arg1	FI					1468:1469	FI	1468:1469	FI	1468:1469	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	97	theme	broilers	1496:1503	arg1	lower					1557:1561	lower	1557:1561	lower	1557:1561	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	97	theme	broilers	1496:1503	arg1	intake					1460:1465	The daily feed intake	1445:1465	The daily feed intake (FI)	1445:1470	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	97	theme	broilers	1496:1503	arg1	gain					1483:1486	weight gain	1476:1486	weight gain (WG)	1476:1491	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	17	97	theme	broilers	1496:1503	arg1	WG					1489:1490	WG	1489:1490	WG	1489:1490	The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly (P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics.
30982351	11	98	theme	quality	1092:1098	arg1	characteristics					1100:1114	The quality characteristics	1088:1114	The quality characteristics of wheat samples	1088:1131	The quality characteristics of wheat samples were in the expected range.
30982351	2	99	theme	poultry	301:307	arg1	industry					309:316	the UK poultry industry	294:316	the UK poultry industry	294:316	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
30982351	14	100	theme	maximum	1277:1283	arg1	range					1285:1289	a maximum range	1275:1289	a maximum range of 1.13 MJ/kg DM between samples	1275:1322	The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples.
30982351	2	101	theme	broiler	338:344	arg1	performance					353:363	broiler growth performance	338:363	broiler growth performance	338:363	The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance.
31002132	0	0	theme	O-linked	93:100	arg1	transferase					122:132	O-linked N-acetylglucosamine transferase	93:132	O-linked N-acetylglucosamine transferase	93:132	MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.
31002132	6	1	link	O-linked	833:840	arg1	target					893:898	a direct target	884:898	a direct target of miRNA-485-5p	884:914	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	1	link	O-linked	833:840	arg1	OGT					875:877	OGT	875:877	OGT	875:877	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	1	link	O-linked	833:840	arg1	transferase					862:872	O-linked N-acetylglucosamine transferase	833:872	O-linked N-acetylglucosamine transferase (OGT)	833:878	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	9	2	theme	EC	1299:1300	arg1	cells					1302:1306	EC cells	1299:1306	EC cells	1299:1306	Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells.
31002132	13	3	theme	EC	1803:1804	arg1	tumorigenesis					1806:1818	EC tumorigenesis	1803:1818	EC tumorigenesis	1803:1818	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	10	4	theme	untranslated	1358:1369	arg1	UTR					1379:1381	UTR	1379:1381	UTR	1379:1381	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	10	4	theme	untranslated	1358:1369	arg1	region					1371:1376	the 3' untranslated region	1351:1376	the 3' untranslated region (UTR) of OGT	1351:1389	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	4	5	from	expression	523:532	arg1	lines					561:565	EC cell lines	553:565	EC cell lines	553:565	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	6	6	theme	O-linked	833:840	arg1	target					893:898	a direct target	884:898	a direct target of miRNA-485-5p	884:914	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	6	theme	O-linked	833:840	arg1	OGT					875:877	OGT	875:877	OGT	875:877	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	6	theme	O-linked	833:840	arg1	transferase					862:872	O-linked N-acetylglucosamine transferase	833:872	O-linked N-acetylglucosamine transferase (OGT)	833:878	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	9	7	theme	control	1186:1192	arg1	groups					1194:1199	the control groups	1182:1199	the control groups	1182:1199	Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells.
31002132	12	8	theme	growth	1685:1690	arg1	inhibition					1666:1675	inhibition	1666:1675	inhibition of cell growth and tumor weight	1666:1707	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	9	9	theme	expression	1206:1215	arg1	miR-485-5p					1217:1226	the expression miR-485-5p	1202:1226	the expression miR-485-5p	1202:1226	Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells.
31002132	8	10	dep	miR-485-5p	1066:1075	arg1	=					1090:1090	=	1090:1090	=	1090:1090	RESULTS The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR.
31002132	8	11	theme	miR-485-5p	1066:1075	arg1	upregulation					1050:1061	The upregulation	1046:1061	The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001)	1046:1143	RESULTS The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR.
31002132	7	12	theme	OGT	1001:1003	arg1	expression					1005:1014	OGT expression	1001:1014	OGT expression	1001:1014	Moreover, we showed that miRNA-485-5p regulated EC tumorigenesis by down-regulating OGT expression in vitro and in vivo.
31002132	13	13	from	applications	1873:1884	arg1	treatment					1892:1900	EC treatment	1889:1900	EC treatment	1889:1900	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	12	14	theme	cell	1680:1683	arg1	growth					1685:1690	cell growth	1680:1690	cell growth	1680:1690	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	10	15	contain	contains	1391:1398	arg1	UTR					1379:1381	UTR	1379:1381	UTR	1379:1381	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	10	15	contain	contains	1391:1398	arg1	region					1371:1376	the 3' untranslated region	1351:1376	the 3' untranslated region (UTR) of OGT	1351:1389	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	10	15	contain	contains	1391:1398	arg2	sequences					1422:1430	one miR-485-5p target sequences	1400:1430	one miR-485-5p target sequences	1400:1430	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	0	16	theme	N-acetylglucosamine	102:120	arg1	transferase					122:132	O-linked N-acetylglucosamine transferase	93:132	O-linked N-acetylglucosamine transferase	93:132	MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.
31002132	3	17	from	expression	391:400	arg1	tissues					422:428	EC tissues	419:428	EC tissues	419:428	Additionally, we found that the expression of miR-485-5p in EC tissues was aberrant.
31002132	10	18	theme	miR-485-5p	1404:1413	arg1	sequences					1422:1430	one miR-485-5p target sequences	1400:1430	one miR-485-5p target sequences	1400:1430	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	5	19	theme	transwell	606:614	arg1	assay					616:620	transwell assay	606:620	transwell assay	606:620	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	12	20	theme	OGT	1629:1631	arg1	expression					1633:1642	OGT expression	1629:1642	OGT expression	1629:1642	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	8	21	dep	RESULTS	1038:1044	arg1	showed					1149:1154	showed	1149:1154	was showed by qRT-PCR	1145:1165	RESULTS The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR.
31002132	6	22	theme	miRNA-485-5p	903:914	arg1	target					893:898	a direct target	884:898	a direct target of miRNA-485-5p	884:914	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	22	theme	miRNA-485-5p	903:914	arg1	transferase					862:872	O-linked N-acetylglucosamine transferase	833:872	O-linked N-acetylglucosamine transferase (OGT)	833:878	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	8	23	theme	fold	1078:1081	arg1	change					1083:1088	fold change	1078:1088	fold change	1078:1088	RESULTS The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR.
31002132	13	24	theme	therapeutic	1861:1871	arg1	applications					1873:1884	therapeutic applications	1861:1884	therapeutic applications in EC treatment	1861:1900	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	12	25	theme	expression	1633:1642	arg1	effects					1618:1624	the rescue effects	1607:1624	the rescue effects of OGT expression on miR-485-5p	1607:1656	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	13	26	theme	EC	1889:1890	arg1	treatment					1892:1900	EC treatment	1889:1900	EC treatment	1889:1900	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	4	27	used	used	499:502	arg2	METHODS					457:463	METHODS	457:463	METHODS	457:463	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	4	27	used	used	499:502	arg2	PATIENTS					444:451	PATIENTS	444:451	PATIENTS	444:451	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	5	28	theme	kit-8	582:586	arg1	assay					596:600	Cell counting kit-8 (CCK-8) assay	568:600	Cell counting kit-8 (CCK-8) assay	568:600	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	2	29	theme	esophageal	312:321	arg1	EC					331:332	EC	331:332	EC	331:332	Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood.
31002132	2	29	theme	esophageal	312:321	arg1	cancer					323:328	esophageal cancer	312:328	esophageal cancer (EC)	312:333	Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood.
31002132	13	30	theme	novel	1841:1845	arg1	miRNA-485-5p					1771:1782	miRNA-485-5p	1771:1782	miRNA-485-5p	1771:1782	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	13	30	theme	novel	1841:1845	arg1	candidate					1847:1855	a novel candidate	1839:1855	a novel candidate for therapeutic applications in EC treatment	1839:1900	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	12	31	theme	CCK-8	1580:1584	arg1	assay					1586:1590	CCK-8 assay	1580:1590	CCK-8 assay	1580:1590	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	3	32	theme	miR-485-5p	405:414	arg1	expression					391:400	the expression	387:400	the expression of miR-485-5p in EC tissues	387:428	Additionally, we found that the expression of miR-485-5p in EC tissues was aberrant.
31002132	3	32	theme	miR-485-5p	405:414	arg1	aberrant					434:441	aberrant	434:441	aberrant	434:441	Additionally, we found that the expression of miR-485-5p in EC tissues was aberrant.
31002132	10	33	theme	one	1400:1402	arg1	sequences					1422:1430	one miR-485-5p target sequences	1400:1430	one miR-485-5p target sequences	1400:1430	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	5	34	theme	miRNA-485-5p	637:648	arg1	overexpression					650:663	miRNA-485-5p overexpression	637:663	miRNA-485-5p overexpression	637:663	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	7	35	theme	EC	965:966	arg1	tumorigenesis					968:980	EC tumorigenesis	965:980	EC tumorigenesis	965:980	Moreover, we showed that miRNA-485-5p regulated EC tumorigenesis by down-regulating OGT expression in vitro and in vivo.
31002132	9	36	theme	cells	1302:1306	arg1	invasion					1287:1294	invasion	1287:1294	invasion	1287:1294	Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells.
31002132	9	36	theme	cells	1302:1306	arg1	proliferation					1257:1269	proliferation	1257:1269	proliferation	1257:1269	Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells.
31002132	9	36	theme	cells	1302:1306	arg1	migration					1272:1280	migration	1272:1280	migration	1272:1280	Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells.
31002132	10	37	theme	OGT	1387:1389	arg1	UTR					1379:1381	UTR	1379:1381	UTR	1379:1381	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	10	37	theme	OGT	1387:1389	arg1	region					1371:1376	the 3' untranslated region	1351:1376	the 3' untranslated region (UTR) of OGT	1351:1389	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	8	38	from	26	1099:1100	arg1	TE-1					1116:1119	TE-1	1116:1119	TE-1	1116:1119	RESULTS The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR.
31002132	8	38	from	26	1099:1100	arg1	ECA109					1105:1110	ECA109	1105:1110	ECA109	1105:1110	RESULTS The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR.
31002132	13	39	theme	tumorigenesis	1806:1818	arg1	miRNA-485-5p					1771:1782	miRNA-485-5p	1771:1782	miRNA-485-5p	1771:1782	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	13	39	theme	tumorigenesis	1806:1818	arg1	suppressor					1789:1798	a suppressor	1787:1798	a suppressor of EC tumorigenesis	1787:1818	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	5	40	theme	cell	675:678	arg1	proliferation					680:692	cell proliferation	675:692	cell proliferation	675:692	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	0	41	theme	esophageal	23:32	arg1	cells					41:45	esophageal cancer cells	23:45	esophageal cancer cells proliferation	23:59	MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.
31002132	11	42	with	co-transfection	1538:1552	arg1	miR-485-5p					1559:1568	miR-485-5p	1559:1568	miR-485-5p	1559:1568	Western blotting and dual-luciferase reporter assay showed that activation of OGT 3'UTR was increased by co-transfection with miR-485-5p.
31002132	12	43	theme	TE1	1723:1725	arg1	cells					1727:1731	TE1 cells	1723:1731	TE1 cells	1723:1731	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	12	44	from	effects	1618:1624	arg1	miR-485-5p					1647:1656	miR-485-5p	1647:1656	miR-485-5p	1647:1656	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	2	45	from	role	288:291	arg1	EC					331:332	EC	331:332	EC	331:332	Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood.
31002132	2	45	from	role	288:291	arg1	cancer					323:328	esophageal cancer	312:328	esophageal cancer (EC)	312:333	Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood.
31002132	5	46	theme	EC	722:723	arg1	lines					730:734	EC cell lines	722:734	EC cell lines	722:734	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	6	47	theme	direct	886:891	arg1	target					893:898	a direct target	884:898	a direct target of miRNA-485-5p	884:914	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	47	theme	direct	886:891	arg1	transferase					862:872	O-linked N-acetylglucosamine transferase	833:872	O-linked N-acetylglucosamine transferase (OGT)	833:878	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	1	48	theme	OBJECTIVE	135:143	arg1	reports					154:160	OBJECTIVE Previous reports	135:160	OBJECTIVE Previous reports	135:160	OBJECTIVE Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types.
31002132	11	49	theme	Western	1433:1439	arg1	blotting					1441:1448	Western blotting	1433:1448	Western blotting	1433:1448	Western blotting and dual-luciferase reporter assay showed that activation of OGT 3'UTR was increased by co-transfection with miR-485-5p.
31002132	1	50	theme	cancer	245:250	arg1	types					252:256	some cancer types	240:256	some cancer types	240:256	OBJECTIVE Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types.
31002132	0	51	theme	cells	41:45	arg1	proliferation					47:59	esophageal cancer cells proliferation	23:59	esophageal cancer cells proliferation	23:59	MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.
31002132	5	52	theme	cell	725:728	arg1	lines					730:734	EC cell lines	722:734	EC cell lines	722:734	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	4	53	theme	Quantitative	465:476	arg1	RT-PCR					478:483	Quantitative RT-PCR	465:483	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR)	444:493	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	4	53	theme	Quantitative	465:476	arg1	qRT-PCR					486:492	qRT-PCR	486:492	qRT-PCR	486:492	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	2	54	theme	biological	277:286	arg1	role					288:291	the biological role	273:291	the biological role of miRNA-485-5p in esophageal cancer (EC)	273:333	Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood.
31002132	0	55	theme	cancer	34:39	arg1	cells					41:45	esophageal cancer cells	23:45	esophageal cancer cells proliferation	23:59	MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.
31002132	5	56	from	proliferation	680:692	arg1	lines					730:734	EC cell lines	722:734	EC cell lines	722:734	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	6	57	theme	reporter	785:792	arg1	assay					794:798	dual-luciferase reporter assay	769:798	dual-luciferase reporter assay	769:798	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	5	58	from	migration	695:703	arg1	lines					730:734	EC cell lines	722:734	EC cell lines	722:734	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	0	59	link	O-linked	93:100	arg1	transferase					122:132	O-linked N-acetylglucosamine transferase	93:132	O-linked N-acetylglucosamine transferase	93:132	MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.
31002132	3	60	theme	EC	419:420	arg1	tissues					422:428	EC tissues	419:428	EC tissues	419:428	Additionally, we found that the expression of miR-485-5p in EC tissues was aberrant.
31002132	4	61	theme	miRNA-485-5p	537:548	arg1	expression					523:532	the expression	519:532	the expression of miRNA-485-5p in EC cell lines	519:565	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	6	62	theme	dual-luciferase	769:783	arg1	assay					794:798	dual-luciferase reporter assay	769:798	dual-luciferase reporter assay	769:798	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	1	63	theme	Previous	145:152	arg1	reports					154:160	OBJECTIVE Previous reports	135:160	OBJECTIVE Previous reports	135:160	OBJECTIVE Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types.
31002132	4	64	theme	cell	556:559	arg1	lines					561:565	EC cell lines	553:565	EC cell lines	553:565	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	13	65	dep	CONCLUSIONS	1734:1744	arg1	suggest					1758:1764	suggest	1758:1764	suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment	1758:1900	CONCLUSIONS Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.
31002132	5	66	theme	Cell	568:571	arg1	CCK-8					589:593	CCK-8	589:593	CCK-8	589:593	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	5	66	theme	Cell	568:571	arg1	kit-8					582:586	Cell counting kit-8	568:586	Cell counting kit-8 (CCK-8) assay	568:600	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	10	67	theme	target	1415:1420	arg1	sequences					1422:1430	one miR-485-5p target sequences	1400:1430	one miR-485-5p target sequences	1400:1430	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	12	68	theme	tumor	1696:1700	arg1	weight					1702:1707	tumor weight	1696:1707	tumor weight	1696:1707	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	4	69	theme	EC	553:554	arg1	lines					561:565	EC cell lines	553:565	EC cell lines	553:565	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	6	70	theme	rescue	805:810	arg1	assay					812:816	rescue assay	805:816	rescue assay	805:816	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	12	71	theme	rescue	1611:1616	arg1	effects					1618:1624	the rescue effects	1607:1624	the rescue effects of OGT expression on miR-485-5p	1607:1656	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	5	72	theme	counting	573:580	arg1	CCK-8					589:593	CCK-8	589:593	CCK-8	589:593	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	5	72	theme	counting	573:580	arg1	kit-8					582:586	Cell counting kit-8	568:586	Cell counting kit-8 (CCK-8) assay	568:600	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	10	73	theme	bioinformatic	1313:1325	arg1	analysis					1327:1334	The bioinformatic analysis	1309:1334	The bioinformatic analysis	1309:1334	The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences.
31002132	2	74	theme	miRNA-485-5p	296:307	arg1	role					288:291	the biological role	273:291	the biological role of miRNA-485-5p in esophageal cancer (EC)	273:333	Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood.
31002132	6	75	theme	Western	751:757	arg1	blotting					759:766	Western blotting	751:766	Western blotting	751:766	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	11	76	theme	dual-luciferase	1454:1468	arg1	assay					1479:1483	dual-luciferase reporter assay	1454:1483	dual-luciferase reporter assay	1454:1483	Western blotting and dual-luciferase reporter assay showed that activation of OGT 3'UTR was increased by co-transfection with miR-485-5p.
31002132	11	77	theme	reporter	1470:1477	arg1	assay					1479:1483	dual-luciferase reporter assay	1454:1483	dual-luciferase reporter assay	1454:1483	Western blotting and dual-luciferase reporter assay showed that activation of OGT 3'UTR was increased by co-transfection with miR-485-5p.
31002132	5	78	from	invasion	710:717	arg1	lines					730:734	EC cell lines	722:734	EC cell lines	722:734	Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines.
31002132	8	79	dep	=	1090:1090	arg1	p<0.001					1136:1142	p<0.001	1136:1142	p<0.001	1136:1142	RESULTS The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR.
31002132	6	80	theme	N-acetylglucosamine	842:860	arg1	target					893:898	a direct target	884:898	a direct target of miRNA-485-5p	884:914	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	80	theme	N-acetylglucosamine	842:860	arg1	OGT					875:877	OGT	875:877	OGT	875:877	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	6	80	theme	N-acetylglucosamine	842:860	arg1	transferase					862:872	O-linked N-acetylglucosamine transferase	833:872	O-linked N-acetylglucosamine transferase (OGT)	833:878	Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p.
31002132	12	81	theme	weight	1702:1707	arg1	inhibition					1666:1675	inhibition	1666:1675	inhibition of cell growth and tumor weight	1666:1707	Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells.
31002132	4	82	dep	PATIENTS	444:451	arg1	RT-PCR					478:483	Quantitative RT-PCR	465:483	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR)	444:493	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	4	82	dep	PATIENTS	444:451	arg1	qRT-PCR					486:492	qRT-PCR	486:492	qRT-PCR	486:492	PATIENTS AND METHODS Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines.
31002132	11	83	theme	OGT	1511:1513	arg1	UTR					1517:1519	OGT 3'UTR	1511:1519	OGT 3'UTR	1511:1519	Western blotting and dual-luciferase reporter assay showed that activation of OGT 3'UTR was increased by co-transfection with miR-485-5p.
30658234	1	0	theme	melatonin	157:165	arg1	molecules					167:175	two melatonin molecules	153:175	two melatonin molecules	153:175	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	3	1	theme	pharmacophores	735:748	arg1	binding					716:722	the simultaneous binding	699:722	the simultaneous binding of the two pharmacophores to dimeric receptors	699:769	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	1	2	theme	agomelatine	252:262	arg1	dimer					264:268	the agomelatine dimer 7	248:270	the agomelatine dimer 7	248:270	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	3	theme	bioluminescence	350:364	arg1	transfer					383:390	bioluminescence resonance energy transfer	350:390	bioluminescence resonance energy transfer (BRET) experiments	350:409	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	3	theme	bioluminescence	350:364	arg1	BRET					393:396	BRET	393:396	BRET	393:396	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	4	theme	β-arrestin	439:448	arg1	assays					462:467	functional cAMP and β-arrestin recruitment assays	419:467	assays	462:467	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	4	5	dep	ligands	781:787	arg1	3c					789:790	3c	789:790	3c	789:790	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	4	5	dep	ligands	781:787	arg1	7					796:796	7	796:796	7	796:796	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	6	6	theme	melatonin	1105:1113	arg1	dimers					1115:1120	O-linked melatonin dimers	1096:1120	O-linked melatonin dimers	1096:1120	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	6	6	theme	melatonin	1105:1113	arg1	tools					1136:1140	promising tools	1126:1140	promising tools to develop signaling pathway-based bivalent melatonin receptor ligands	1126:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	1	7	theme	resonance	366:374	arg1	transfer					383:390	bioluminescence resonance energy transfer	350:390	bioluminescence resonance energy transfer (BRET) experiments	350:409	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	7	theme	resonance	366:374	arg1	BRET					393:396	BRET	393:396	BRET	393:396	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	8	theme	recruitment	450:460	arg1	assays					462:467	functional cAMP and β-arrestin recruitment assays	419:467	assays	462:467	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	3	9	theme	Bivalent	575:582	arg1	ligands					584:590	Bivalent ligands	575:590	Bivalent ligands 3a-e	575:595	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	6	10	theme	melatonin	1186:1194	arg1	ligands					1205:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	1	11	theme	energy	376:381	arg1	transfer					383:390	bioluminescence resonance energy transfer	350:390	bioluminescence resonance energy transfer (BRET) experiments	350:409	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	11	theme	energy	376:381	arg1	BRET					393:396	BRET	393:396	BRET	393:396	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	4	12	theme	β-arrestin	889:898	arg1	pathway					900:906	the β-arrestin pathway	885:906	the β-arrestin pathway	885:906	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	5	13	theme	agonistic	1000:1008	arg1	properties					1010:1019	inverse agonistic properties	992:1019	inverse agonistic properties	992:1019	Interestingly, 3c (20 atoms spacer) shows inverse agonistic properties at MT2 on the Gi/cAMP pathway.
30658234	2	14	theme	3a-e	519:522	arg1	affinity					507:514	The binding affinity	495:514	The binding affinity of 3a-e	495:522	The binding affinity of 3a-e generally increased with increasing linker length.
30658234	1	15	theme	transfer	383:390	arg1	experiments					399:409	bioluminescence resonance energy transfer (BRET) experiments	350:409	bioluminescence resonance energy transfer (BRET) experiments	350:409	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	0	16	link	O-linked	0:7	arg1	dimers					19:24	O-linked melatonin dimers	0:24	O-linked melatonin dimers as bivalent ligands	0:44	O-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors.
30658234	3	17	dep	increased	597:605	arg1	compared					647:654	compared	647:654	increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors	597:769	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	4	18	theme	Gi/cAMP	858:864	arg1	pathway					866:872	the Gi/cAMP pathway	854:872	the Gi/cAMP pathway	854:872	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	6	19	theme	pathway-based	1163:1175	arg1	ligands					1205:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	5	20	theme	inverse	992:998	arg1	properties					1010:1019	inverse agonistic properties	992:1019	inverse agonistic properties	992:1019	Interestingly, 3c (20 atoms spacer) shows inverse agonistic properties at MT2 on the Gi/cAMP pathway.
30658234	6	21	theme	O-linked	1096:1103	arg1	dimers					1115:1120	O-linked melatonin dimers	1096:1120	O-linked melatonin dimers	1096:1120	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	6	21	theme	O-linked	1096:1103	arg1	tools					1136:1140	promising tools	1126:1140	promising tools to develop signaling pathway-based bivalent melatonin receptor ligands	1126:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	0	22	theme	melatonin	9:17	arg1	dimers					19:24	O-linked melatonin dimers	0:24	O-linked melatonin dimers as bivalent ligands	0:44	O-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors.
30658234	3	23	theme	ligands	584:590	arg1	3a-e					592:595	Bivalent ligands 3a-e	575:595	Bivalent ligands 3a-e	575:595	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	1	24	theme	methoxy	189:195	arg1	atoms					204:208	the methoxy oxygen atoms	185:208	the methoxy oxygen atoms with spacers spanning 16-24 atoms	185:242	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	0	25	theme	O-linked	0:7	arg1	dimers					19:24	O-linked melatonin dimers	0:24	O-linked melatonin dimers as bivalent ligands	0:44	O-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors.
30658234	1	26	theme	MT2	480:482	arg1	receptors					484:492	MT2 receptors	480:492	MT2 receptors	480:492	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	6	27	theme	bivalent	1177:1184	arg1	ligands					1205:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	1	28	theme	oxygen	197:202	arg1	atoms					204:208	the methoxy oxygen atoms	185:208	the methoxy oxygen atoms with spacers spanning 16-24 atoms	185:242	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	29	theme	dimeric	97:103	arg1	analogues					115:123	dimeric melatonin analogues 3a-e	97:128	dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms	97:242	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	3	30	theme	dimeric	753:759	arg1	receptors					761:769	dimeric receptors	753:769	dimeric receptors	753:769	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	2	31	theme	linker	560:565	arg1	length					567:572	linker length	560:572	linker length	560:572	The binding affinity of 3a-e generally increased with increasing linker length.
30658234	1	32	theme	melatonin	105:113	arg1	analogues					115:123	dimeric melatonin analogues 3a-e	97:128	dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms	97:242	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	33	from	receptors	484:492	arg1	assays					462:467	functional cAMP and β-arrestin recruitment assays	419:467	assays	462:467	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	33	from	receptors	484:492	arg1	cAMP					430:433	functional cAMP and β-arrestin recruitment assays	419:467	cAMP	430:433	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	34	with	atoms	204:208	arg1	spacers					215:221	spacers	215:221	spacers spanning 16-24 atoms	215:242	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	4	35	dep	exhibited	798:806	arg1	compared					908:915	compared	908:915	compared to their monomeric counterparts	908:947	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	6	36	link	O-linked	1096:1103	arg1	dimers					1115:1120	O-linked melatonin dimers	1096:1120	O-linked melatonin dimers	1096:1120	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	6	36	link	O-linked	1096:1103	arg1	tools					1136:1140	promising tools	1126:1140	promising tools to develop signaling pathway-based bivalent melatonin receptor ligands	1126:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	0	37	theme	bivalent	29:36	arg1	ligands					38:44	bivalent ligands	29:44	bivalent ligands	29:44	O-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors.
30658234	4	38	theme	functional	829:838	arg1	properties					840:849	functional properties	829:849	functional properties	829:849	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	3	39	dep	to	637:638	arg1	up					634:635	up	634:635	up	634:635	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	0	40	theme	dimeric	56:62	arg1	receptors					74:82	dimeric melatonin receptors	56:82	dimeric melatonin receptors	56:82	O-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors.
30658234	2	41	theme	binding	499:505	arg1	affinity					507:514	The binding affinity	495:514	The binding affinity of 3a-e	495:522	The binding affinity of 3a-e generally increased with increasing linker length.
30658234	5	42	theme	Gi/cAMP	1035:1041	arg1	pathway					1043:1049	the Gi/cAMP pathway	1031:1049	the Gi/cAMP pathway	1031:1049	Interestingly, 3c (20 atoms spacer) shows inverse agonistic properties at MT2 on the Gi/cAMP pathway.
30658234	1	43	theme	analogues	115:123	arg1	dimer					264:268	the agomelatine dimer 7	248:270	the agomelatine dimer 7	248:270	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	43	theme	analogues	115:123	arg1	series					87:92	A series	85:92	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms	85:242	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	3	44	theme	simultaneous	703:714	arg1	binding					716:722	the simultaneous binding	699:722	the simultaneous binding of the two pharmacophores to dimeric receptors	699:769	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	1	45	theme	-iodomelatonin	319:332	arg1	assays					342:347	2-[125-I]-iodomelatonin binding assays	310:347	2-[125-I]-iodomelatonin binding assays	310:347	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	3	46	theme	BRET	607:610	arg1	signals					612:618	BRET signals	607:618	BRET signals of MT1 dimers up to	607:638	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	1	47	theme	3a-e	125:128	arg1	analogues					115:123	dimeric melatonin analogues 3a-e	97:128	dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms	97:242	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	48	theme	binding	334:340	arg1	assays					342:347	2-[125-I]-iodomelatonin binding assays	310:347	2-[125-I]-iodomelatonin binding assays	310:347	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	4	49	theme	monomeric	926:934	arg1	counterparts					936:947	their monomeric counterparts	920:947	their monomeric counterparts	920:947	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	1	50	theme	functional	419:428	arg1	cAMP					430:433	functional cAMP and β-arrestin recruitment assays	419:467	cAMP	430:433	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	4	51	theme	important	808:816	arg1	changes					818:824	important changes	808:824	important changes in functional properties	808:849	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	1	52	from	MT1	472:474	arg1	assays					462:467	functional cAMP and β-arrestin recruitment assays	419:467	assays	462:467	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	1	52	from	MT1	472:474	arg1	cAMP					430:433	functional cAMP and β-arrestin recruitment assays	419:467	cAMP	430:433	A series of dimeric melatonin analogues 3a-e obtained by connecting two melatonin molecules through the methoxy oxygen atoms with spacers spanning 16-24 atoms and the agomelatine dimer 7 were synthesized and characterized in 2-[125-I]-iodomelatonin binding assays, bioluminescence resonance energy transfer (BRET) experiments, and in functional cAMP and β-arrestin recruitment assays at MT1 and MT2 receptors.
30658234	4	53	theme	Bivalent	772:779	arg1	ligands					781:787	Bivalent ligands	772:787	Bivalent ligands 3c and 7	772:796	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	6	54	theme	receptor	1196:1203	arg1	ligands					1205:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	3	55	theme	monomeric	663:671	arg1	ligand					681:686	the monomeric control ligand	659:686	the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors	659:769	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	6	56	theme	promising	1126:1134	arg1	dimers					1115:1120	O-linked melatonin dimers	1096:1120	O-linked melatonin dimers	1096:1120	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	6	56	theme	promising	1126:1134	arg1	tools					1136:1140	promising tools	1126:1140	promising tools to develop signaling pathway-based bivalent melatonin receptor ligands	1126:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	3	57	theme	control	673:679	arg1	ligand					681:686	the monomeric control ligand	659:686	the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors	659:769	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	3	58	theme	MT1	623:625	arg1	dimers					627:632	MT1 dimers	623:632	MT1 dimers	623:632	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
30658234	4	59	from	changes	818:824	arg1	properties					840:849	functional properties	829:849	functional properties	829:849	Bivalent ligands 3c and 7 exhibited important changes in functional properties on the Gi/cAMP pathway but not on the β-arrestin pathway compared to their monomeric counterparts.
30658234	5	60	theme	atoms	972:976	arg1	3c					965:966	3c	965:966	3c (20 atoms spacer)	965:984	Interestingly, 3c (20 atoms spacer) shows inverse agonistic properties at MT2 on the Gi/cAMP pathway.
30658234	5	60	theme	atoms	972:976	arg1	spacer					978:983	20 atoms spacer	969:983	20 atoms spacer	969:983	Interestingly, 3c (20 atoms spacer) shows inverse agonistic properties at MT2 on the Gi/cAMP pathway.
30658234	0	61	theme	melatonin	64:72	arg1	receptors					74:82	dimeric melatonin receptors	56:82	dimeric melatonin receptors	56:82	O-linked melatonin dimers as bivalent ligands targeting dimeric melatonin receptors.
30658234	6	62	theme	signaling	1153:1161	arg1	ligands					1205:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	signaling pathway-based bivalent melatonin receptor ligands	1153:1211	In conclusion, these findings indicate that O-linked melatonin dimers are promising tools to develop signaling pathway-based bivalent melatonin receptor ligands.
30658234	3	63	theme	dimers	627:632	arg1	signals					612:618	BRET signals	607:618	BRET signals of MT1 dimers up to	607:638	Bivalent ligands 3a-e increased BRET signals of MT1 dimers up to 3-fold compared to the monomeric control ligand indicating the simultaneous binding of the two pharmacophores to dimeric receptors.
31821735	0	0	theme	Plasmodium falciparum	70:90	arg1	parasite					92:99	the Plasmodium falciparum parasite	66:99	the Plasmodium falciparum parasite	66:99	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	4	1	theme	information	667:677	arg1	information					667:677	information	667:677	information on the localization of these proteins on the cell surfaces of RBCs	667:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	4	1	theme	information	667:677	arg1	amount					657:662	a fair amount	650:662	a fair amount of information on the localization of these proteins on the cell surfaces of RBCs	650:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	5	2	theme	proteins	933:940	arg1	insertion					920:928	the cotranslational insertion	900:928	the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite	900:992	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	5	2	theme	proteins	933:940	arg1	step					872:875	The first step	862:875	The first step of export	862:885	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	2	3	theme	open	343:346	arg1	STEVOR					363:368	STEVOR	363:368	STEVOR	363:368	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	3	theme	open	343:346	arg1	frame					356:360	variable open reading frame	334:360	subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	321:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	5	4	theme	RIFIN	1043:1047	arg1	insertion					1024:1032	the insertion	1020:1032	the insertion of three RIFIN and two STEVOR proteins into the ER membrane	1020:1092	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	3	5	link	parasite-derived	440:455	arg1	proteins					457:464	these parasite-derived proteins	434:464	these parasite-derived proteins	434:464	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	2	6	theme	variable	334:341	arg1	STEVOR					363:368	STEVOR	363:368	STEVOR	363:368	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	6	theme	variable	334:341	arg1	frame					356:360	variable open reading frame	334:360	subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	321:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	4	7	from	information	667:677	arg1	surfaces					729:736	the cell surfaces	720:736	the cell surfaces of RBCs	720:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	4	7	from	information	667:677	arg1	localization					686:697	the localization	682:697	the localization of these proteins	682:715	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	6	8	theme	experimental	1124:1135	arg1	system					1137:1142	a well-established experimental system	1105:1142	a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane	1105:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	7	9	theme	Ncyt-Ccyt	1489:1497	arg1	topology					1477:1484	an overall topology	1466:1484	an overall topology of Ncyt-Ccyt	1466:1497	Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt.
31821735	3	10	theme	blood	623:627	arg1	flow					629:632	blood flow	623:632	blood flow	623:632	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	4	11	theme	RBCs	741:744	arg1	surfaces					729:736	the cell surfaces	720:736	the cell surfaces of RBCs	720:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	2	12	theme	repetitive	278:287	arg1	RIFIN					310:314	RIFIN	310:314	RIFIN	310:314	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	12	theme	repetitive	278:287	arg1	family					302:307	the repetitive interspersed family	274:307	the repetitive interspersed family (RIFIN)	274:315	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	0	13	theme	parasite	92:99	arg1	RIFIN					37:41	RIFIN	37:41	RIFIN	37:41	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	0	13	theme	parasite	92:99	arg1	proteins					54:61	STEVOR proteins	47:61	STEVOR proteins	47:61	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	5	14	theme	cotranslational	904:918	arg1	insertion					920:928	the cotranslational insertion	900:928	the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite	900:992	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	5	14	theme	cotranslational	904:918	arg1	step					872:875	The first step	862:875	The first step of export	862:885	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	6	15	theme	well-established	1107:1122	arg1	system					1137:1142	a well-established experimental system	1105:1142	a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane	1105:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	3	16	theme	uninfected	538:547	arg1	rosetting					556:564	rosetting	556:564	rosetting	556:564	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	3	16	theme	uninfected	538:547	arg1	cells					549:553	uninfected cells	538:553	uninfected cells (rosetting)	538:565	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	4	17	from	amount	657:662	arg1	surfaces					729:736	the cell surfaces	720:736	the cell surfaces of RBCs	720:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	4	17	from	amount	657:662	arg1	localization					686:697	the localization	682:697	the localization of these proteins	682:715	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	1	18	theme	parasite	115:122	arg1	Plasmodium					124:133	The malarial parasite Plasmodium	102:133	The malarial parasite Plasmodium	102:133	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	3	19	theme	infected	520:527	arg1	cells					529:533	infected cells	520:533	infected cells	520:533	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	1	20	theme	cell	167:170	arg1	surfaces					172:179	the cell surfaces	163:179	the cell surfaces of red blood cells (RBCs)	163:205	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	6	21	theme	sites	1180:1184	arg1	glycosylation					1163:1175	N-linked glycosylation	1154:1175	N-linked glycosylation of sites within the protein	1154:1203	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	6	21	theme	sites	1180:1184	arg1	measure					1210:1216	a measure	1208:1216	a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane	1208:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	4	22	from	surfaces	729:736	arg1	information					667:677	information	667:677	information on the localization of these proteins on the cell surfaces of RBCs	667:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	4	22	from	surfaces	729:736	arg1	amount					657:662	a fair amount	650:662	a fair amount of information on the localization of these proteins on the cell surfaces of RBCs	650:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	3	23	theme	cells	529:533	arg1	adhesion					508:515	the adhesion	504:515	the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow	504:632	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	3	24	theme	infected	481:488	arg1	RBCs					490:493	infected RBCs	481:493	infected RBCs	481:493	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	7	25	theme	overall	1469:1475	arg1	topology					1477:1484	an overall topology	1466:1484	an overall topology of Ncyt-Ccyt	1466:1497	Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt.
31821735	3	26	attach	presence	422:429	arg1	surfaces					469:476	surfaces	469:476	surfaces of infected RBCs	469:493	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	3	26	attach	presence	422:429	arg2	proteins					457:464	these parasite-derived proteins	434:464	these parasite-derived proteins	434:464	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	0	27	theme	Membrane	0:7	arg1	integration					9:19	Membrane integration	0:19	Membrane integration	0:19	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	5	28	theme	ER	1082:1083	arg1	membrane					1085:1092	the ER membrane	1078:1092	the ER membrane	1078:1092	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	2	29	theme	family	302:307	arg1	members					263:269	members	263:269	members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	263:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	1	30	theme	red	184:186	arg1	cells					194:198	red blood cells	184:198	red blood cells (RBCs)	184:205	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	1	30	theme	red	184:186	arg1	RBCs					201:204	RBCs	201:204	RBCs	201:204	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	6	31	theme	insertion	1251:1259	arg1	extent					1232:1237	the extent	1228:1237	the extent of membrane insertion and the topology it assumes when inserted into the ER membrane	1228:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	2	32	theme	interspersed	289:300	arg1	RIFIN					310:314	RIFIN	310:314	RIFIN	310:314	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	32	theme	interspersed	289:300	arg1	family					302:307	the repetitive interspersed family	274:307	the repetitive interspersed family (RIFIN)	274:315	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	1	33	theme	blood	188:192	arg1	cells					194:198	red blood cells	184:198	red blood cells (RBCs)	184:205	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	1	33	theme	blood	188:192	arg1	RBCs					201:204	RBCs	201:204	RBCs	201:204	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	5	34	theme	export	880:885	arg1	insertion					920:928	the cotranslational insertion	900:928	the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite	900:992	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	5	34	theme	export	880:885	arg1	step					872:875	The first step	862:875	The first step of export	862:885	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	6	35	link	N-linked	1154:1161	arg1	glycosylation					1163:1175	N-linked glycosylation	1154:1175	N-linked glycosylation of sites within the protein	1154:1203	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	6	35	link	N-linked	1154:1161	arg1	measure					1210:1216	a measure	1208:1216	a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane	1208:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	6	36	theme	membrane	1242:1249	arg1	insertion					1251:1259	membrane insertion	1242:1259	membrane insertion	1242:1259	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	1	37	theme	malarial	106:113	arg1	parasite					115:122	The malarial parasite	102:122	The malarial parasite Plasmodium	102:133	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	6	38	dep	topology	1269:1276	arg1	assumes					1281:1287	assumes	1281:1287	assumes when inserted into the ER membrane	1281:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	1	39	theme	cells	194:198	arg1	surfaces					172:179	the cell surfaces	163:179	the cell surfaces of red blood cells (RBCs)	163:205	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	0	40	theme	RIFIN	37:41	arg1	topology					25:32	topology	25:32	topology	25:32	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	0	40	theme	RIFIN	37:41	arg1	integration					9:19	Membrane integration	0:19	Membrane integration	0:19	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	6	41	theme	N-linked	1154:1161	arg1	glycosylation					1163:1175	N-linked glycosylation	1154:1175	N-linked glycosylation of sites within the protein	1154:1203	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	6	41	theme	N-linked	1154:1161	arg1	measure					1210:1216	a measure	1208:1216	a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane	1208:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	4	42	theme	fair	652:655	arg1	information					667:677	information	667:677	information on the localization of these proteins on the cell surfaces of RBCs	667:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	4	42	theme	fair	652:655	arg1	amount					657:662	a fair amount	650:662	a fair amount of information on the localization of these proteins on the cell surfaces of RBCs	650:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	2	43	theme	proteins	381:388	arg1	RIFIN					310:314	RIFIN	310:314	RIFIN	310:314	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	43	theme	proteins	381:388	arg1	family					371:376	subtelomeric variable open reading frame (STEVOR) family	321:376	subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	321:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	43	theme	proteins	381:388	arg1	family					302:307	the repetitive interspersed family	274:307	the repetitive interspersed family (RIFIN)	274:315	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	44	theme	family	371:376	arg1	members					263:269	members	263:269	members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	263:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	5	45	theme	STEVOR	1057:1062	arg1	proteins					1064:1071	three RIFIN and two STEVOR proteins	1037:1071	proteins	1064:1071	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	3	46	theme	vascular	578:585	arg1	endothelium					587:597	the vascular endothelium	574:597	the vascular endothelium potentially obstructing blood flow	574:632	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	3	47	theme	parasite-derived	440:455	arg1	proteins					457:464	these parasite-derived proteins	434:464	these parasite-derived proteins	434:464	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	0	48	theme	STEVOR	47:52	arg1	proteins					54:61	STEVOR proteins	47:61	STEVOR proteins	47:61	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	5	49	theme	proteins	1064:1071	arg1	insertion					1024:1032	the insertion	1020:1032	the insertion of three RIFIN and two STEVOR proteins into the ER membrane	1020:1092	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	6	50	gly	glycosylation	1163:1175	arg1	sites					1180:1184	sites	1180:1184	sites within the protein	1180:1203	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	2	51	theme	subtelomeric	321:332	arg1	family					371:376	subtelomeric variable open reading frame (STEVOR) family	321:376	subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	321:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	6	52	theme	ER	1312:1313	arg1	membrane					1315:1322	the ER membrane	1308:1322	the ER membrane	1308:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
31821735	4	53	dep	topologies	816:825	arg1	they					827:830	they	827:830	they	827:830	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	2	54	from	family	371:376	arg1	Plasmodium falciparum					395:415	Plasmodium falciparum	395:415	Plasmodium falciparum	395:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	3	55	theme	RBCs	490:493	arg1	surfaces					469:476	surfaces	469:476	surfaces of infected RBCs	469:493	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	1	56	theme	own	147:149	arg1	proteins					151:158	its own proteins	143:158	its own proteins	143:158	The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection.
31821735	2	57	theme	proteins	246:253	arg1	Examples					225:232	Examples	225:232	Examples of exported proteins	225:253	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	4	58	theme	proteins	708:715	arg1	localization					686:697	the localization	682:697	the localization of these proteins	682:715	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	3	59	from	presence	422:429	arg1	surfaces					469:476	surfaces	469:476	surfaces of infected RBCs	469:493	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	5	60	theme	parasite	985:992	arg1	ER					974:975	ER	974:975	ER	974:975	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	5	60	theme	parasite	985:992	arg1	reticulum					963:971	the endoplasmic reticulum	947:971	the endoplasmic reticulum (ER) of the parasite	947:992	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	2	61	theme	exported	237:244	arg1	proteins					246:253	exported proteins	237:253	exported proteins	237:253	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	4	62	theme	cell	724:727	arg1	surfaces					729:736	the cell surfaces	720:736	the cell surfaces of RBCs	720:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	7	63	dep	transmembranes	1380:1393	arg1	1					1401:1401	1	1401:1401	1	1401:1401	Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt.
31821735	7	63	dep	transmembranes	1380:1393	arg1	3					1407:1407	3	1407:1407	3	1407:1407	Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt.
31821735	5	64	theme	first	866:870	arg1	insertion					920:928	the cotranslational insertion	900:928	the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite	900:992	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	5	64	theme	first	866:870	arg1	step					872:875	The first step	862:875	The first step of export	862:885	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	2	65	from	family	302:307	arg1	Plasmodium falciparum					395:415	Plasmodium falciparum	395:415	Plasmodium falciparum	395:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	3	66	theme	proteins	457:464	arg1	presence					422:429	The presence	418:429	The presence of these parasite-derived proteins on surfaces of infected RBCs	418:493	The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow.
31821735	2	67	theme	frame	356:360	arg1	family					371:376	subtelomeric variable open reading frame (STEVOR) family	321:376	subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	321:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	4	68	from	localization	686:697	arg1	information					667:677	information	667:677	information on the localization of these proteins on the cell surfaces of RBCs	667:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	4	68	from	localization	686:697	arg1	amount					657:662	a fair amount	650:662	a fair amount of information on the localization of these proteins on the cell surfaces of RBCs	650:744	While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process.
31821735	0	69	theme	proteins	54:61	arg1	topology					25:32	topology	25:32	topology	25:32	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	0	69	theme	proteins	54:61	arg1	integration					9:19	Membrane integration	0:19	Membrane integration	0:19	Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite.
31821735	5	70	theme	endoplasmic	951:961	arg1	ER					974:975	ER	974:975	ER	974:975	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	5	70	theme	endoplasmic	951:961	arg1	reticulum					963:971	the endoplasmic reticulum	947:971	the endoplasmic reticulum (ER) of the parasite	947:992	The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane.
31821735	2	71	from	Plasmodium falciparum	395:415	arg1	proteins					381:388	proteins	381:388	proteins from Plasmodium falciparum	381:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	71	from	Plasmodium falciparum	395:415	arg1	RIFIN					310:314	RIFIN	310:314	RIFIN	310:314	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	71	from	Plasmodium falciparum	395:415	arg1	family					371:376	subtelomeric variable open reading frame (STEVOR) family	321:376	subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	321:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	71	from	Plasmodium falciparum	395:415	arg1	family					302:307	the repetitive interspersed family	274:307	the repetitive interspersed family (RIFIN)	274:315	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	72	theme	reading	348:354	arg1	STEVOR					363:368	STEVOR	363:368	STEVOR	363:368	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	2	72	theme	reading	348:354	arg1	frame					356:360	variable open reading frame	334:360	subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum	321:415	Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum.
31821735	6	73	theme	topology	1269:1276	arg1	extent					1232:1237	the extent	1228:1237	the extent of membrane insertion and the topology it assumes when inserted into the ER membrane	1228:1322	We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane.
29671116	1	0	link	N-linked	64:71	arg1	glycosylation					73:85	N-linked glycosylation	64:85	N-linked glycosylation (NLG)	64:91	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	0	link	N-linked	64:71	arg1	essential					136:144	essential	136:144	essential	136:144	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	0	link	N-linked	64:71	arg1	modification					115:126	a co-translational modification	96:126	a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins	96:238	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	0	link	N-linked	64:71	arg1	NLG					88:90	NLG	88:90	NLG	88:90	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	7	1	theme	MPDU1	1160:1164	arg1	expression					1166:1175	MPDU1 expression	1160:1175	MPDU1 expression in Kato III cells	1160:1193	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	2	2	theme	14-sugar	313:320	arg1	carbohydrate					322:333	a 14-sugar carbohydrate	311:333	a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO)	311:379	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	6	3	theme	adhesion	1100:1107	arg1	molecule					1109:1116	the cell adhesion molecule	1091:1116	the cell adhesion molecule CEACAM1	1091:1124	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	7	4	theme	expression	1166:1175	arg1	restoration					1145:1155	the restoration	1141:1155	the restoration of MPDU1 expression in Kato III cells	1141:1193	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	8	5	theme	LLO	1450:1452	arg1	biosynthesis					1454:1465	LLO biosynthesis	1450:1465	LLO biosynthesis	1450:1465	These experiments also confirmed that protein levels of CEACAM-1, which functions in cell adhesion, is dependent on LLO biosynthesis in vivo.
29671116	6	6	theme	proteins	1039:1046	arg1	expression					1008:1017	the expression	1004:1017	the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1	1004:1124	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	4	7	theme	synthesis	625:633	arg1	model					602:606	a model	600:606	a model	600:606	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	6	8	theme	expression	913:922	arg1	microarray					924:933	an expression microarray	910:933	an expression microarray	910:933	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	6	9	theme	membrane	1030:1037	arg1	proteins					1039:1046	several membrane proteins	1022:1046	several membrane proteins	1022:1046	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	6	9	theme	membrane	1030:1037	arg1	molecule					1109:1116	the cell adhesion molecule	1091:1116	the cell adhesion molecule CEACAM1	1091:1124	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	6	9	theme	membrane	1030:1037	arg1	ADAM-15					1079:1085	the metalloprotease ADAM-15	1059:1085	the metalloprotease ADAM-15	1059:1085	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	5	10	contain	have	737:740	arg1	cells					717:721	Kato III cells	708:721	Kato III cells lacking MPDU1	708:735	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	5	10	contain	have	737:740	arg2	hallmarks					750:758	all the hallmarks	742:758	all the hallmarks	742:758	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	5	10	contain	have	737:740	arg2	formation					849:857	the formation	845:857	the formation of truncated LLOs	845:875	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	5	10	contain	have	737:740	arg2	sensitivity					818:828	altered sensitivity	810:828	altered sensitivity to lectins	810:839	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	7	11	from	cells	1189:1193	arg1	restoration					1145:1155	the restoration	1141:1155	the restoration of MPDU1 expression in Kato III cells	1141:1193	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	9	12	theme	Kato	1476:1479	arg1	cells					1485:1489	Kato III cells	1476:1489	Kato III cells	1476:1489	Kato III cells and the MPDU1-rescued Kato IIIM cells therefore provide a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo.
29671116	9	13	theme	IIIM	1518:1521	arg1	cells					1523:1527	the MPDU1-rescued Kato IIIM cells	1495:1527	the MPDU1-rescued Kato IIIM cells	1495:1527	Kato III cells and the MPDU1-rescued Kato IIIM cells therefore provide a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo.
29671116	1	14	theme	secretory	216:224	arg1	glycoproteins					226:238	secretory glycoproteins	216:238	secretory glycoproteins	216:238	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	5	15	theme	truncated	862:870	arg1	LLOs					872:875	truncated LLOs	862:875	truncated LLOs	862:875	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	6	16	theme	cell	1095:1098	arg1	molecule					1109:1116	the cell adhesion molecule	1091:1116	the cell adhesion molecule CEACAM1	1091:1124	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	3	17	theme	LLO	495:497	arg1	biosynthesis					499:510	LLO biosynthesis	495:510	LLO biosynthesis	495:510	The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking.
29671116	3	18	theme	hamster	458:464	arg1	systems					466:472	Chinese hamster systems	450:472	Chinese hamster systems	450:472	The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking.
29671116	2	19	theme	en	291:292	arg1	transfer					299:306	en bloc transfer	291:306	en bloc transfer	291:306	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	9	20	theme	LLO	1602:1604	arg1	biosynthesis					1606:1617	defective LLO biosynthesis	1592:1617	defective LLO biosynthesis	1592:1617	Kato III cells and the MPDU1-rescued Kato IIIM cells therefore provide a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo.
29671116	6	21	dep	molecule	1109:1116	arg1	CEACAM1					1118:1124	CEACAM1	1118:1124	the cell adhesion molecule CEACAM1	1091:1124	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	2	22	theme	Efficient	241:249	arg1	NLG					251:253	Efficient NLG	241:253	Efficient NLG	241:253	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	5	23	theme	cell	789:792	arg1	line					794:797	a glycosylation-deficient cell line	763:797	a glycosylation-deficient cell line	763:797	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	1	24	theme	glycoproteins	226:238	arg1	folding					154:160	folding	154:160	folding	154:160	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	24	theme	glycoproteins	226:238	arg1	stability					163:171	stability	163:171	stability	163:171	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	24	theme	glycoproteins	226:238	arg1	trafficking					178:188	trafficking	178:188	trafficking	178:188	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	4	25	contain	possessing	636:645	arg2	deletion					660:667	a homozygous deletion	647:667	a homozygous deletion of the LLO biosynthesis factor	647:698	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	4	25	contain	possessing	636:645	arg2	MPDU1					701:705	MPDU1	701:705	MPDU1	701:705	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	4	25	contain	possessing	636:645	arg1	model					602:606	a model	600:606	a model	600:606	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	6	26	theme	protein	939:945	arg1	levels					947:952	protein levels	939:952	protein levels	939:952	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	9	27	theme	biosynthesis	1606:1617	arg1	consequences					1576:1587	the consequences	1572:1587	the consequences of defective LLO biosynthesis	1572:1617	Kato III cells and the MPDU1-rescued Kato IIIM cells therefore provide a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo.
29671116	6	28	theme	several	1022:1028	arg1	proteins					1039:1046	several membrane proteins	1022:1046	several membrane proteins	1022:1046	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	6	28	theme	several	1022:1028	arg1	molecule					1109:1116	the cell adhesion molecule	1091:1116	the cell adhesion molecule CEACAM1	1091:1124	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	6	28	theme	several	1022:1028	arg1	ADAM-15					1079:1085	the metalloprotease ADAM-15	1059:1085	the metalloprotease ADAM-15	1059:1085	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	2	29	theme	lipid-linked	346:357	arg1	LLO					376:378	LLO	376:378	LLO	376:378	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	2	29	theme	lipid-linked	346:357	arg1	oligosaccharide					359:373	a lipid-linked oligosaccharide	344:373	a lipid-linked oligosaccharide (LLO)	344:379	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	1	30	theme	co-translational	98:113	arg1	glycosylation					73:85	N-linked glycosylation	64:85	N-linked glycosylation (NLG)	64:91	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	30	theme	co-translational	98:113	arg1	modification					115:126	a co-translational modification	96:126	a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins	96:238	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	30	theme	co-translational	98:113	arg1	essential					136:144	essential	136:144	essential	136:144	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	31	theme	N-linked	64:71	arg1	glycosylation					73:85	N-linked glycosylation	64:85	N-linked glycosylation (NLG)	64:91	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	31	theme	N-linked	64:71	arg1	essential					136:144	essential	136:144	essential	136:144	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	31	theme	N-linked	64:71	arg1	modification					115:126	a co-translational modification	96:126	a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins	96:238	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	31	theme	N-linked	64:71	arg1	NLG					88:90	NLG	88:90	NLG	88:90	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	7	32	from	restoration	1145:1155	arg1	cells					1189:1193	Kato III cells	1180:1193	Kato III cells	1180:1193	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	4	33	theme	homozygous	649:658	arg1	MPDU1					701:705	MPDU1	701:705	MPDU1	701:705	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	4	33	theme	homozygous	649:658	arg1	deletion					660:667	a homozygous deletion	647:667	a homozygous deletion of the LLO biosynthesis factor	647:698	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	1	34	gly	glycoproteins	226:238	arg1	glycoproteins					226:238	secretory glycoproteins	216:238	secretory glycoproteins	216:238	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	5	35	theme	line	794:797	arg1	hallmarks					750:758	all the hallmarks	742:758	all the hallmarks	742:758	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	5	35	theme	line	794:797	arg1	formation					849:857	the formation	845:857	the formation of truncated LLOs	845:875	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	5	35	theme	line	794:797	arg1	sensitivity					818:828	altered sensitivity	810:828	altered sensitivity to lectins	810:839	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	9	36	theme	MPDU1-rescued	1499:1511	arg1	cells					1523:1527	the MPDU1-rescued Kato IIIM cells	1495:1527	the MPDU1-rescued Kato IIIM cells	1495:1527	Kato III cells and the MPDU1-rescued Kato IIIM cells therefore provide a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo.
29671116	8	37	theme	CEACAM-1	1390:1397	arg1	levels					1380:1385	protein levels	1372:1385	protein levels	1372:1385	These experiments also confirmed that protein levels of CEACAM-1, which functions in cell adhesion, is dependent on LLO biosynthesis in vivo.
29671116	6	38	from	changes	993:999	arg1	expression					1008:1017	the expression	1004:1017	the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1	1004:1124	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	2	39	theme	stepwise	268:275	arg1	synthesis					277:285	stepwise synthesis	268:285	stepwise synthesis	268:285	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	7	40	theme	xenografts	1322:1331	arg1	analysis					1304:1311	analysis	1304:1311	analysis of tumor xenografts	1304:1331	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	4	41	theme	gastric	569:575	arg1	cells					584:588	Kato III human gastric cancer cells	554:588	Kato III human gastric cancer cells	554:588	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	5	42	theme	LLOs	872:875	arg1	formation					849:857	the formation	845:857	the formation of truncated LLOs	845:875	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	5	42	theme	LLOs	872:875	arg1	sensitivity					818:828	altered sensitivity	810:828	altered sensitivity to lectins	810:839	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	6	43	theme	transcription	890:902	arg1	Analysis					878:885	Analysis	878:885	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array	878:984	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	3	44	theme	human	479:483	arg1	models					485:490	human models	479:490	human models of LLO biosynthesis	479:510	The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking.
29671116	4	45	theme	LLO	676:678	arg1	factor					693:698	the LLO biosynthesis factor	672:698	the LLO biosynthesis factor	672:698	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	4	46	theme	human	563:567	arg1	cells					584:588	Kato III human gastric cancer cells	554:588	Kato III human gastric cancer cells	554:588	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	5	47	theme	Kato	708:711	arg1	cells					717:721	Kato III cells	708:721	Kato III cells lacking MPDU1	708:735	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	6	48	theme	metalloprotease	1063:1077	arg1	ADAM-15					1079:1085	the metalloprotease ADAM-15	1059:1085	the metalloprotease ADAM-15	1059:1085	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	7	49	theme	cell-cell	1239:1247	arg1	adhesion					1249:1256	increased cell-cell adhesion	1229:1256	increased cell-cell adhesion	1229:1256	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	1	50	dep	folding	154:160	arg1	the					150:152	the	150:152	the	150:152	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	7	51	theme	adhesion	1249:1256	arg1	phenotype					1216:1224	a clear phenotype	1208:1224	a clear phenotype of increased cell-cell adhesion	1208:1256	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	7	51	theme	adhesion	1249:1256	arg1	finding					1261:1267	a finding	1259:1267	a finding that was confirmed in vivo through analysis of tumor xenografts	1259:1331	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	3	52	theme	biosynthesis	402:413	arg1	genetics					386:393	The genetics	382:393	The genetics of LLO biosynthesis	382:413	The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking.
29671116	0	53	theme	cell	28:31	arg1	adhesion					33:40	cell adhesion	28:40	cell adhesion	28:40	MPDU1 regulates CEACAM1 and cell adhesion in vitro and in vivo.
29671116	4	54	theme	factor	693:698	arg1	MPDU1					701:705	MPDU1	701:705	MPDU1	701:705	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	4	54	theme	factor	693:698	arg1	deletion					660:667	a homozygous deletion	647:667	a homozygous deletion of the LLO biosynthesis factor	647:698	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	5	55	theme	glycosylation-deficient	765:787	arg1	line					794:797	a glycosylation-deficient cell line	763:797	a glycosylation-deficient cell line	763:797	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	4	56	theme	biosynthesis	680:691	arg1	factor					693:698	the LLO biosynthesis factor	672:698	the LLO biosynthesis factor	672:698	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	5	57	theme	altered	810:816	arg1	sensitivity					818:828	altered sensitivity	810:828	altered sensitivity to lectins	810:839	Kato III cells lacking MPDU1 have all the hallmarks of a glycosylation-deficient cell line, including altered sensitivity to lectins and the formation of truncated LLOs.
29671116	6	58	theme	antibody	971:978	arg1	array					980:984	a proteome antibody array	960:984	a proteome antibody array	960:984	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	2	59	link	lipid-linked	346:357	arg1	LLO					376:378	LLO	376:378	LLO	376:378	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	2	59	link	lipid-linked	346:357	arg1	oligosaccharide					359:373	a lipid-linked oligosaccharide	344:373	a lipid-linked oligosaccharide (LLO)	344:379	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	8	60	theme	cell	1419:1422	arg1	adhesion					1424:1431	cell adhesion	1419:1431	cell adhesion	1419:1431	These experiments also confirmed that protein levels of CEACAM-1, which functions in cell adhesion, is dependent on LLO biosynthesis in vivo.
29671116	7	61	theme	tumor	1316:1320	arg1	xenografts					1322:1331	tumor xenografts	1316:1331	tumor xenografts	1316:1331	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	9	62	theme	defective	1592:1600	arg1	biosynthesis					1606:1617	defective LLO biosynthesis	1592:1617	defective LLO biosynthesis	1592:1617	Kato III cells and the MPDU1-rescued Kato IIIM cells therefore provide a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo.
29671116	3	63	theme	Chinese	450:456	arg1	systems					466:472	Chinese hamster systems	450:472	Chinese hamster systems	450:472	The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking.
29671116	7	64	from	expression	1166:1175	arg1	cells					1189:1193	Kato III cells	1180:1193	Kato III cells	1180:1193	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	8	65	theme	protein	1372:1378	arg1	levels					1380:1385	protein levels	1372:1385	protein levels	1372:1385	These experiments also confirmed that protein levels of CEACAM-1, which functions in cell adhesion, is dependent on LLO biosynthesis in vivo.
29671116	4	66	theme	deficient	611:619	arg1	synthesis					625:633	deficient LLO synthesis	611:633	deficient LLO synthesis	611:633	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	2	67	theme	bloc	294:297	arg1	transfer					299:306	en bloc transfer	291:306	en bloc transfer	291:306	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	3	68	theme	biosynthesis	499:510	arg1	models					485:490	human models	479:490	human models of LLO biosynthesis	479:510	The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking.
29671116	6	69	theme	proteome	962:969	arg1	array					980:984	a proteome antibody array	960:984	a proteome antibody array	960:984	Analysis of transcription using an expression microarray and protein levels using a proteome antibody array reveal changes in the expression of several membrane proteins, including the metalloprotease ADAM-15 and the cell adhesion molecule CEACAM1.
29671116	7	70	theme	increased	1229:1237	arg1	adhesion					1249:1256	increased cell-cell adhesion	1229:1256	increased cell-cell adhesion	1229:1256	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	2	71	dep	synthesis	277:285	arg1	the					264:266	the	264:266	the	264:266	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	1	72	theme	transmembrane	193:205	arg1	TM					208:209	transmembrane (TM)	193:210	transmembrane (TM)	193:210	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	4	73	theme	cancer	577:582	arg1	cells					584:588	Kato III human gastric cancer cells	554:588	Kato III human gastric cancer cells	554:588	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	9	74	theme	novel	1549:1553	arg1	model					1555:1559	a novel model	1547:1559	a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo	1547:1643	Kato III cells and the MPDU1-rescued Kato IIIM cells therefore provide a novel model to examine the consequences of defective LLO biosynthesis both in vitro and in vivo.
29671116	4	75	theme	LLO	621:623	arg1	synthesis					625:633	deficient LLO synthesis	611:633	deficient LLO synthesis	611:633	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	3	76	theme	LLO	398:400	arg1	biosynthesis					402:413	LLO biosynthesis	398:413	LLO biosynthesis	398:413	The genetics of LLO biosynthesis have been established in yeast and Chinese hamster systems, but human models of LLO biosynthesis are lacking.
29671116	7	77	theme	Kato	1180:1183	arg1	cells					1189:1193	Kato III cells	1180:1193	Kato III cells	1180:1193	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	4	78	theme	Kato	554:557	arg1	cells					584:588	Kato III human gastric cancer cells	554:588	Kato III human gastric cancer cells	554:588	In this study we report that Kato III human gastric cancer cells represent a model of deficient LLO synthesis, possessing a homozygous deletion of the LLO biosynthesis factor, MPDU1.
29671116	7	79	theme	clear	1210:1214	arg1	phenotype					1216:1224	a clear phenotype	1208:1224	a clear phenotype of increased cell-cell adhesion	1208:1256	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	7	79	theme	clear	1210:1214	arg1	finding					1261:1267	a finding	1259:1267	a finding that was confirmed in vivo through analysis of tumor xenografts	1259:1331	Surprisingly, the restoration of MPDU1 expression in Kato III cells demonstrated a clear phenotype of increased cell-cell adhesion, a finding that was confirmed in vivo through analysis of tumor xenografts.
29671116	2	80	theme	carbohydrate	322:333	arg1	transfer					299:306	en bloc transfer	291:306	en bloc transfer	291:306	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	2	80	theme	carbohydrate	322:333	arg1	synthesis					277:285	stepwise synthesis	268:285	stepwise synthesis	268:285	Efficient NLG requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (LLO).
29671116	1	81	theme	TM	208:209	arg1	folding					154:160	folding	154:160	folding	154:160	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	81	theme	TM	208:209	arg1	stability					163:171	stability	163:171	stability	163:171	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
29671116	1	81	theme	TM	208:209	arg1	trafficking					178:188	trafficking	178:188	trafficking	178:188	N-linked glycosylation (NLG) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (TM) and secretory glycoproteins.
31526925	5	0	link	N-linked	687:694	arg1	glycosylation					696:708	N-linked glycosylation	687:708	N-linked glycosylation	687:708	In addition, our data demonstrated that N-linked glycosylation was involved in the transport of MC-LR by Oatp1a5.
31526925	1	1	theme	hypothalamic-pituitary-testis	271:299	arg1	axis					301:304	hypothalamic-pituitary-testis axis	271:304	hypothalamic-pituitary-testis axis	271:304	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	6	2	theme	glycosylation	795:807	arg1	Asn492					826:831	Asn492	826:831	Asn492	826:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	2	theme	glycosylation	795:807	arg1	Asn483					815:820	Asn483	815:820	Asn483	815:820	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	2	theme	glycosylation	795:807	arg1	sites					809:813	N-linked glycosylation sites	786:813	N-linked glycosylation sites Asn483 and Asn492	786:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	2	3	theme	transporting	325:336	arg1	transporter					378:388	a critical transporter	367:388	a critical transporter for the uptake of MC-LR by GnRH neurons	367:428	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	3	theme	transporting	325:336	arg1	polypeptide					338:348	The organic anion transporting polypeptide 1a5	307:352	The organic anion transporting polypeptide 1a5 (Oatp1a5)	307:362	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	3	theme	transporting	325:336	arg1	Oatp1a5					355:361	Oatp1a5	355:361	Oatp1a5	355:361	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	6	4	theme	N-linked	786:793	arg1	Asn492					826:831	Asn492	826:831	Asn492	826:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	4	theme	N-linked	786:793	arg1	Asn483					815:820	Asn483	815:820	Asn483	815:820	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	4	theme	N-linked	786:793	arg1	sites					809:813	N-linked glycosylation sites	786:813	N-linked glycosylation sites Asn483 and Asn492	786:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	2	5	theme	anion	319:323	arg1	transporter					378:388	a critical transporter	367:388	a critical transporter for the uptake of MC-LR by GnRH neurons	367:428	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	5	theme	anion	319:323	arg1	polypeptide					338:348	The organic anion transporting polypeptide 1a5	307:352	The organic anion transporting polypeptide 1a5 (Oatp1a5)	307:362	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	5	theme	anion	319:323	arg1	Oatp1a5					355:361	Oatp1a5	355:361	Oatp1a5	355:361	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	5	6	gly	glycosylation	696:708	arg1	transport					730:738	the transport	726:738	the transport of MC-LR by Oatp1a5	726:758	In addition, our data demonstrated that N-linked glycosylation was involved in the transport of MC-LR by Oatp1a5.
31526925	3	7	theme	process	493:499	arg1	elusive					511:517	elusive	511:517	elusive	511:517	However, the underlying molecular mechanisms of the transport process are still elusive.
31526925	3	7	theme	process	493:499	arg1	mechanisms					465:474	the underlying molecular mechanisms	440:474	the underlying molecular mechanisms of the transport process	440:499	However, the underlying molecular mechanisms of the transport process are still elusive.
31526925	2	8	theme	organic	311:317	arg1	transporter					378:388	a critical transporter	367:388	a critical transporter for the uptake of MC-LR by GnRH neurons	367:428	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	8	theme	organic	311:317	arg1	polypeptide					338:348	The organic anion transporting polypeptide 1a5	307:352	The organic anion transporting polypeptide 1a5 (Oatp1a5)	307:362	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	8	theme	organic	311:317	arg1	Oatp1a5					355:361	Oatp1a5	355:361	Oatp1a5	355:361	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	9	theme	GnRH	417:420	arg1	neurons					422:428	GnRH neurons	417:428	GnRH neurons	417:428	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	1	10	theme	Microcystin-leucine	91:109	arg1	MC-LR					121:125	MC-LR	121:125	MC-LR	121:125	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	1	10	theme	Microcystin-leucine	91:109	arg1	arginine					111:118	Microcystin-leucine arginine	91:118	Microcystin-leucine arginine (MC-LR)	91:126	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	7	11	theme	male	1057:1060	arg1	health					1075:1080	male reproductive health	1057:1080	male reproductive health	1057:1080	In summary, the study furthered our understanding of mechanisms that the uptake of MC-LR by GnRH neurons and laid a theoretical foundation for preventing MC-LR from injuring male reproductive health.
31526925	6	12	link	N-linked	786:793	arg1	Asn492					826:831	Asn492	826:831	Asn492	826:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	12	link	N-linked	786:793	arg1	Asn483					815:820	Asn483	815:820	Asn483	815:820	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	12	link	N-linked	786:793	arg1	sites					809:813	N-linked glycosylation sites	786:813	N-linked glycosylation sites Asn483 and Asn492	786:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	13	theme	Oatp1a5	874:880	arg1	function					862:869	the transport function	848:869	the transport function of Oatp1a5	848:880	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	2	14	theme	MC-LR	408:412	arg1	uptake					398:403	the uptake	394:403	the uptake of MC-LR by GnRH neurons	394:428	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	7	15	theme	reproductive	1062:1073	arg1	health					1075:1080	male reproductive health	1057:1080	male reproductive health	1057:1080	In summary, the study furthered our understanding of mechanisms that the uptake of MC-LR by GnRH neurons and laid a theoretical foundation for preventing MC-LR from injuring male reproductive health.
31526925	3	16	theme	underlying	444:453	arg1	elusive					511:517	elusive	511:517	elusive	511:517	However, the underlying molecular mechanisms of the transport process are still elusive.
31526925	3	16	theme	underlying	444:453	arg1	mechanisms					465:474	the underlying molecular mechanisms	440:474	the underlying molecular mechanisms of the transport process	440:499	However, the underlying molecular mechanisms of the transport process are still elusive.
31526925	0	17	theme	Oatp1a5-mediated	17:32	arg1	arginine					54:61	Oatp1a5-mediated microcystin-leucine arginine	17:61	Oatp1a5-mediated microcystin-leucine arginine	17:61	The mechanism of Oatp1a5-mediated microcystin-leucine arginine entering into GnRH neurons.
31526925	4	18	theme	transmembrane	553:565	arg1	domains					567:573	the transmembrane domains 2, 8, and 9	549:585	the transmembrane domains 2, 8, and 9	549:585	In this study, we found that the transmembrane domains 2, 8, and 9 played important roles in transporting function of Oatp1a5.
31526925	5	19	theme	N-linked	687:694	arg1	glycosylation					696:708	N-linked glycosylation	687:708	N-linked glycosylation	687:708	In addition, our data demonstrated that N-linked glycosylation was involved in the transport of MC-LR by Oatp1a5.
31526925	7	20	theme	mechanisms	936:945	arg1	understanding					919:931	our understanding	915:931	our understanding of mechanisms that the uptake of MC-LR by GnRH neurons	915:986	In summary, the study furthered our understanding of mechanisms that the uptake of MC-LR by GnRH neurons and laid a theoretical foundation for preventing MC-LR from injuring male reproductive health.
31526925	3	21	theme	transport	483:491	arg1	process					493:499	the transport process	479:499	the transport process	479:499	However, the underlying molecular mechanisms of the transport process are still elusive.
31526925	6	22	theme	transport	852:860	arg1	function					862:869	the transport function	848:869	the transport function of Oatp1a5	848:880	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	23	dep	sites	809:813	arg1	Asn492					826:831	Asn492	826:831	Asn492	826:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	23	dep	sites	809:813	arg1	Asn483					815:820	Asn483	815:820	Asn483	815:820	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	23	dep	sites	809:813	arg1	sites					809:813	N-linked glycosylation sites	786:813	N-linked glycosylation sites Asn483 and Asn492	786:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	1	24	theme	GnRH	215:218	arg1	levels					220:225	serum GnRH levels	209:225	serum GnRH levels	209:225	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	0	25	theme	arginine	54:61	arg1	mechanism					4:12	The mechanism	0:12	The mechanism of Oatp1a5-mediated microcystin-leucine arginine	0:61	The mechanism of Oatp1a5-mediated microcystin-leucine arginine entering into GnRH neurons.
31526925	4	26	theme	Oatp1a5	638:644	arg1	function					626:633	function	626:633	function of Oatp1a5	626:644	In this study, we found that the transmembrane domains 2, 8, and 9 played important roles in transporting function of Oatp1a5.
31526925	1	27	theme	levels	220:225	arg1	decline					198:204	decline	198:204	decline of serum GnRH levels resulting in male reproductive toxicity	198:265	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	0	28	theme	microcystin-leucine	34:52	arg1	arginine					54:61	Oatp1a5-mediated microcystin-leucine arginine	17:61	Oatp1a5-mediated microcystin-leucine arginine	17:61	The mechanism of Oatp1a5-mediated microcystin-leucine arginine entering into GnRH neurons.
31526925	6	29	gly	glycosylation	795:807	arg2	sites					809:813	N-linked glycosylation sites	786:813	N-linked glycosylation sites Asn483 and Asn492	786:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	29	gly	glycosylation	795:807	arg2	Asn483					815:820	Asn483	815:820	Asn483	815:820	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	6	29	gly	glycosylation	795:807	arg2	Asn492					826:831	Asn492	826:831	Asn492	826:831	Moreover, we showed that N-linked glycosylation sites Asn483 and Asn492 were vital for the transport function of Oatp1a5.
31526925	3	30	theme	molecular	455:463	arg1	elusive					511:517	elusive	511:517	elusive	511:517	However, the underlying molecular mechanisms of the transport process are still elusive.
31526925	3	30	theme	molecular	455:463	arg1	mechanisms					465:474	the underlying molecular mechanisms	440:474	the underlying molecular mechanisms of the transport process	440:499	However, the underlying molecular mechanisms of the transport process are still elusive.
31526925	2	31	theme	critical	369:376	arg1	polypeptide					338:348	The organic anion transporting polypeptide 1a5	307:352	The organic anion transporting polypeptide 1a5 (Oatp1a5)	307:362	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	2	31	theme	critical	369:376	arg1	transporter					378:388	a critical transporter	367:388	a critical transporter for the uptake of MC-LR by GnRH neurons	367:428	The organic anion transporting polypeptide 1a5 (Oatp1a5) is a critical transporter for the uptake of MC-LR by GnRH neurons.
31526925	7	32	theme	GnRH	975:978	arg1	neurons					980:986	GnRH neurons	975:986	GnRH neurons	975:986	In summary, the study furthered our understanding of mechanisms that the uptake of MC-LR by GnRH neurons and laid a theoretical foundation for preventing MC-LR from injuring male reproductive health.
31526925	1	33	theme	gonadotropin-releasing	140:161	arg1	GnRH					172:175	GnRH	172:175	GnRH	172:175	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	1	33	theme	gonadotropin-releasing	140:161	arg1	hormone					163:169	gonadotropin-releasing hormone	140:169	gonadotropin-releasing hormone (GnRH) neurons	140:184	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	4	34	theme	important	594:602	arg1	roles					604:608	important roles	594:608	important roles	594:608	In this study, we found that the transmembrane domains 2, 8, and 9 played important roles in transporting function of Oatp1a5.
31526925	7	35	theme	theoretical	999:1009	arg1	foundation					1011:1020	a theoretical foundation	997:1020	a theoretical foundation for preventing MC-LR from injuring male reproductive health	997:1080	In summary, the study furthered our understanding of mechanisms that the uptake of MC-LR by GnRH neurons and laid a theoretical foundation for preventing MC-LR from injuring male reproductive health.
31526925	7	36	theme	MC-LR	966:970	arg1	uptake					956:961	the uptake	952:961	the uptake of MC-LR by GnRH neurons	952:986	In summary, the study furthered our understanding of mechanisms that the uptake of MC-LR by GnRH neurons and laid a theoretical foundation for preventing MC-LR from injuring male reproductive health.
31526925	1	37	theme	hormone	163:169	arg1	neurons					178:184	gonadotropin-releasing hormone (GnRH) neurons	140:184	gonadotropin-releasing hormone (GnRH) neurons	140:184	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	1	38	theme	male	240:243	arg1	toxicity					258:265	male reproductive toxicity	240:265	male reproductive toxicity	240:265	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	5	39	theme	MC-LR	743:747	arg1	transport					730:738	the transport	726:738	the transport of MC-LR by Oatp1a5	726:758	In addition, our data demonstrated that N-linked glycosylation was involved in the transport of MC-LR by Oatp1a5.
31526925	1	40	theme	serum	209:213	arg1	levels					220:225	serum GnRH levels	209:225	serum GnRH levels	209:225	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	1	41	theme	reproductive	245:256	arg1	toxicity					258:265	male reproductive toxicity	240:265	male reproductive toxicity	240:265	Microcystin-leucine arginine (MC-LR) enters into gonadotropin-releasing hormone (GnRH) neurons and induces decline of serum GnRH levels resulting in male reproductive toxicity via hypothalamic-pituitary-testis axis.
31526925	0	42	theme	GnRH	77:80	arg1	neurons					82:88	GnRH neurons	77:88	GnRH neurons	77:88	The mechanism of Oatp1a5-mediated microcystin-leucine arginine entering into GnRH neurons.
31266804	9	0	gly	N-glycosylation	1750:1764	arg2	sites					1766:1770	the two TRPC6 N-glycosylation sites	1736:1770	the two TRPC6 N-glycosylation sites	1736:1770	However, mutating the two TRPC6 N-glycosylation sites abrogated the cytotoxicity of mutant TRPC6 and reduced its surface expression.
31266804	9	0	gly	N-glycosylation	1750:1764	arg2	two					1740:1742	two	1740:1742	two	1740:1742	However, mutating the two TRPC6 N-glycosylation sites abrogated the cytotoxicity of mutant TRPC6 and reduced its surface expression.
31266804	2	1	theme	human	287:291	arg1	channel					299:305	the human TRPC6 channel	283:305	the human TRPC6 channel	283:305	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	4	2	theme	essential	726:734	arg1	insertase					846:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	4	2	theme	essential	726:734	arg1	proteins					717:724	several proteins	709:724	several proteins	709:724	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	1	3	theme	C	199:199	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	3	theme	C	199:199	arg1	TRPC6					211:215	TRPC6	211:215	TRPC6	211:215	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	3	theme	C	199:199	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	9	4	theme	TRPC6	1809:1813	arg1	cytotoxicity					1786:1797	the cytotoxicity	1782:1797	the cytotoxicity of mutant TRPC6	1782:1813	However, mutating the two TRPC6 N-glycosylation sites abrogated the cytotoxicity of mutant TRPC6 and reduced its surface expression.
31266804	4	5	theme	TRPC6	740:744	arg1	expression					754:763	TRPC6 protein expression	740:763	TRPC6 protein expression	740:763	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	8	6	from	cytotoxicity	1682:1693	arg1	podocytes					1707:1715	cultured podocytes	1698:1715	cultured podocytes	1698:1715	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	3	7	from	cytotoxic	526:534	arg1	cells					548:552	cultured cells	539:552	cultured cells	539:552	Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in cultured cells.
31266804	2	8	theme	autosomal-dominant	313:330	arg1	glomerulosclerosis					348:365	autosomal-dominant focal segmental glomerulosclerosis	313:365	autosomal-dominant focal segmental glomerulosclerosis	313:365	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	5	9	theme	signal	939:944	arg1	pathway					1006:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	0	10	theme	channel	130:136	arg1	TRPC6					138:142	the nonselective cation channel TRPC6	106:142	the nonselective cation channel TRPC6	106:142	Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6.
31266804	10	11	theme	ER	1904:1905	arg1	translocation					1907:1919	TMEM208-mediated ER translocation	1887:1919	TMEM208-mediated ER translocation	1887:1919	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	9	12	theme	surface	1831:1837	arg1	expression					1839:1848	its surface expression	1827:1848	its surface expression	1827:1848	However, mutating the two TRPC6 N-glycosylation sites abrogated the cytotoxicity of mutant TRPC6 and reduced its surface expression.
31266804	4	13	theme	several	709:715	arg1	insertase					846:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	4	13	theme	several	709:715	arg1	proteins					717:724	several proteins	709:724	several proteins	709:724	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	5	14	theme	putative	915:922	arg1	protein					890:896	transmembrane protein 208	876:900	transmembrane protein 208 (TMEM208)	876:910	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	5	14	theme	putative	915:922	arg1	component					924:932	a putative component	913:932	a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway	913:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	8	15	theme	TRPC6	1540:1544	arg1	influx					1585:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	4	16	theme	endoplasmic	780:790	arg1	ER					803:804	ER	803:804	ER	803:804	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	4	16	theme	endoplasmic	780:790	arg1	reticulum					792:800	endoplasmic reticulum	780:800	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	10	17	theme	multipass	1932:1940	arg1	proteins					1956:1963	multipass transmembrane proteins	1932:1963	multipass transmembrane proteins	1932:1963	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	5	18	theme	ER	985:986	arg1	pathway					1006:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	8	19	theme	variant-mediated	1563:1578	arg1	influx					1585:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	2	20	theme	Gain-of-function	253:268	arg1	mutations					270:278	Gain-of-function mutations	253:278	Gain-of-function mutations in the human TRPC6 channel	253:305	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	5	21	theme	pathway	1006:1012	arg1	protein					890:896	transmembrane protein 208	876:900	transmembrane protein 208 (TMEM208)	876:910	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	5	21	theme	pathway	1006:1012	arg1	component					924:932	a putative component	913:932	a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway	913:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	2	22	theme	molecular	376:384	arg1	components					386:395	the molecular components	372:395	the molecular components involved in disease development	372:427	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	5	23	theme	particle-independent	958:977	arg1	pathway					1006:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	8	24	theme	extracellular	1596:1608	arg1	kinase					1627:1632	extracellular signal-regulated kinase	1596:1632	extracellular signal-regulated kinase activation	1596:1643	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	1	25	theme	channel	181:187	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	25	theme	channel	181:187	arg1	TRPC6					211:215	TRPC6	211:215	TRPC6	211:215	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	25	theme	channel	181:187	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	8	26	link	N-linked	1512:1519	arg1	glycans					1521:1527	complex N-linked glycans	1504:1527	complex N-linked glycans	1504:1527	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	27	theme	kinase	1627:1632	arg1	activation					1634:1643	extracellular signal-regulated kinase activation	1596:1643	extracellular signal-regulated kinase activation	1596:1643	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	4	28	theme	transmembrane	832:844	arg1	insertase					846:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	1	29	theme	Transient	145:153	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	29	theme	Transient	145:153	arg1	TRPC6					211:215	TRPC6	211:215	TRPC6	211:215	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	29	theme	Transient	145:153	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	8	30	theme	β-1,2-N-acetylglucosaminyltransferase	1425:1461	arg1	Deletion					1378:1385	Deletion	1378:1385	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans,	1378:1528	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	0	31	theme	nonselective	110:121	arg1	channel					130:136	the nonselective cation channel	106:136	the nonselective cation channel TRPC6	106:142	Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6.
31266804	5	32	theme	TRPC6	1052:1056	arg1	expression					1038:1047	expression	1038:1047	expression of TRPC6 and several other ion channels and transporters	1038:1104	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	2	33	theme	disease	409:415	arg1	development					417:427	disease development	409:427	disease development	409:427	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	0	34	theme	Transmembrane	0:12	arg1	insertases					14:23	Transmembrane insertases	0:23	Transmembrane insertases	0:23	Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6.
31266804	4	35	theme	genome-wide	586:596	arg1	screen					609:614	a genome-wide CRISPR/Cas screen	584:614	a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity	584:692	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	4	36	theme	protein	816:822	arg1	insertase					846:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	3	37	theme	TRPC6	500:504	arg1	variants					514:521	gain-of-function TRPC6 channel variants	483:521	gain-of-function TRPC6 channel variants	483:521	Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in cultured cells.
31266804	8	38	gly	-glycoprotein	1411:1423	arg1	-glycoprotein					1411:1423	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	1390:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	1390:1469	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	2	39	from	mutations	270:278	arg1	channel					299:305	the human TRPC6 channel	283:305	the human TRPC6 channel	283:305	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	1	40	theme	receptor	155:162	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	40	theme	receptor	155:162	arg1	TRPC6					211:215	TRPC6	211:215	TRPC6	211:215	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	40	theme	receptor	155:162	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	6	41	theme	TRPC6	1107:1111	arg1	expression					1113:1122	TRPC6 expression	1107:1122	TRPC6 expression	1107:1122	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	5	42	theme	transmembrane	876:888	arg1	component					924:932	a putative component	913:932	a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway	913:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	5	42	theme	transmembrane	876:888	arg1	protein					890:896	transmembrane protein 208	876:900	transmembrane protein 208 (TMEM208)	876:910	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	5	42	theme	transmembrane	876:888	arg1	TMEM208					903:909	TMEM208	903:909	TMEM208	903:909	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	7	43	theme	N-linked	1346:1353	arg1	glycosylation					1363:1375	N-linked protein glycosylation	1346:1375	N-linked protein glycosylation	1346:1375	Additionally enriched among the screen hits were genes involved in N-linked protein glycosylation.
31266804	8	44	theme	cultured	1698:1705	arg1	podocytes					1707:1715	cultured podocytes	1698:1715	cultured podocytes	1698:1715	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	45	theme	complex	1504:1510	arg1	glycans					1521:1527	complex N-linked glycans	1504:1527	complex N-linked glycans	1504:1527	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	3	46	theme	variants	514:521	arg1	overexpression					465:478	overexpression	465:478	overexpression of gain-of-function TRPC6 channel variants	465:521	Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in cultured cells.
31266804	5	47	theme	several	1062:1068	arg1	channels					1080:1087	several other ion channels	1062:1087	several other ion channels	1062:1087	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	6	48	theme	repeat	1189:1194	arg1	WDR83OS					1223:1229	WDR83OS	1223:1229	WDR83OS	1223:1229	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	6	48	theme	repeat	1189:1194	arg1	domain					1196:1201	the previously uncharacterized WD repeat domain	1155:1201	the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS)	1155:1230	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	8	49	theme	glycans	1521:1527	arg1	generation					1490:1499	the generation	1486:1499	the generation of complex N-linked glycans	1486:1527	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	1	50	theme	expressed	230:238	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	50	theme	expressed	230:238	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	5	51	theme	ion	1076:1078	arg1	channels					1080:1087	several other ion channels	1062:1087	several other ion channels	1062:1087	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	6	52	theme	uncharacterized	1170:1184	arg1	WDR83OS					1223:1229	WDR83OS	1223:1229	WDR83OS	1223:1229	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	6	52	theme	uncharacterized	1170:1184	arg1	domain					1196:1201	the previously uncharacterized WD repeat domain	1155:1201	the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS)	1155:1230	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	4	53	theme	TRPC6-associated	664:679	arg1	cytotoxicity					681:692	TRPC6-associated cytotoxicity	664:692	TRPC6-associated cytotoxicity	664:692	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	3	54	theme	cultured	539:546	arg1	cells					548:552	cultured cells	539:552	cultured cells	539:552	Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in cultured cells.
31266804	3	55	from	cells	548:552	arg1	cytotoxic					526:534	cytotoxic	526:534	cytotoxic	526:534	Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in cultured cells.
31266804	2	56	theme	TRPC6	293:297	arg1	channel					299:305	the human TRPC6 channel	283:305	the human TRPC6 channel	283:305	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	1	57	theme	subfamily	189:197	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	57	theme	subfamily	189:197	arg1	TRPC6					211:215	TRPC6	211:215	TRPC6	211:215	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	57	theme	subfamily	189:197	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	9	58	theme	mutant	1802:1807	arg1	TRPC6					1809:1813	mutant TRPC6	1802:1813	mutant TRPC6	1802:1813	However, mutating the two TRPC6 N-glycosylation sites abrogated the cytotoxicity of mutant TRPC6 and reduced its surface expression.
31266804	10	59	theme	TMEM208-mediated	1887:1902	arg1	translocation					1907:1919	TMEM208-mediated ER translocation	1887:1919	TMEM208-mediated ER translocation	1887:1919	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	2	60	theme	focal	332:336	arg1	glomerulosclerosis					348:365	autosomal-dominant focal segmental glomerulosclerosis	313:365	autosomal-dominant focal segmental glomerulosclerosis	313:365	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	0	61	theme	TRPC6	138:142	arg1	trafficking					77:87	trafficking	77:87	trafficking	77:87	Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6.
31266804	0	61	theme	TRPC6	138:142	arg1	activity					94:101	activity	94:101	activity	94:101	Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6.
31266804	0	61	theme	TRPC6	138:142	arg1	synthesis					66:74	synthesis	66:74	synthesis	66:74	Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6.
31266804	10	62	theme	translocation	1907:1919	arg1	targets					1876:1882	the targets	1872:1882	the targets of TMEM208-mediated ER translocation	1872:1919	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	5	63	theme	SND	980:982	arg1	pathway					1006:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	8	64	theme	gain-of-function	1546:1561	arg1	influx					1585:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	10	65	theme	transmembrane	1942:1954	arg1	proteins					1956:1963	multipass transmembrane proteins	1932:1963	multipass transmembrane proteins	1932:1963	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	8	66	theme	Ca2+	1580:1583	arg1	influx					1585:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	TRPC6 gain-of-function variant-mediated Ca2+ influx	1540:1590	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	6	67	dep	domain	1196:1201	arg1	strand					1215:1220	83 opposite strand	1203:1220	the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS)	1155:1230	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	5	68	theme	protein-targeting	988:1004	arg1	pathway					1006:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	7	69	link	N-linked	1346:1353	arg1	glycosylation					1363:1375	N-linked protein glycosylation	1346:1375	N-linked protein glycosylation	1346:1375	Additionally enriched among the screen hits were genes involved in N-linked protein glycosylation.
31266804	10	70	theme	TRPC6	1982:1986	arg1	N-glycosylation					1988:2002	TRPC6 N-glycosylation	1982:2002	TRPC6 N-glycosylation	1982:2002	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	4	71	theme	reticulum	792:800	arg1	insertase					846:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	7	72	theme	enriched	1292:1299	arg1	hits					1318:1321	Additionally enriched among the screen hits	1279:1321	Additionally enriched among the screen hits	1279:1321	Additionally enriched among the screen hits were genes involved in N-linked protein glycosylation.
31266804	5	73	theme	recognition	946:956	arg1	pathway					1006:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	a signal recognition particle-independent (SND) ER protein-targeting pathway	937:1012	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	8	74	theme	signal-regulated	1610:1625	arg1	kinase					1627:1632	extracellular signal-regulated kinase	1596:1632	extracellular signal-regulated kinase activation	1596:1643	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	4	75	theme	protein	746:752	arg1	expression					754:763	TRPC6 protein expression	740:763	TRPC6 protein expression	740:763	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	1	76	theme	cation	174:179	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	76	theme	cation	174:179	arg1	TRPC6					211:215	TRPC6	211:215	TRPC6	211:215	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	76	theme	cation	174:179	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	8	77	theme	mannosyl	1394:1401	arg1	MGAT1					1464:1468	MGAT1	1464:1468	MGAT1	1464:1468	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	77	theme	mannosyl	1394:1401	arg1	β-1,2-N-acetylglucosaminyltransferase					1425:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	1390:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	1390:1469	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	78	theme	HEK	1648:1650	arg1	cells					1652:1656	HEK cells	1648:1656	HEK cells	1648:1656	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	79	theme	α-1,3-	1404:1409	arg1	MGAT1					1464:1468	MGAT1	1464:1468	MGAT1	1464:1468	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	79	theme	α-1,3-	1404:1409	arg1	β-1,2-N-acetylglucosaminyltransferase					1425:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	1390:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	1390:1469	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	4	80	theme	complex	824:830	arg1	insertase					846:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	0	81	theme	cation	123:128	arg1	channel					130:136	the nonselective cation channel	106:136	the nonselective cation channel TRPC6	106:142	Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6.
31266804	8	82	theme	-glycoprotein	1411:1423	arg1	MGAT1					1464:1468	MGAT1	1464:1468	MGAT1	1464:1468	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	82	theme	-glycoprotein	1411:1423	arg1	β-1,2-N-acetylglucosaminyltransferase					1425:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	1390:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	1390:1469	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	4	83	theme	CRISPR/Cas	598:607	arg1	screen					609:614	a genome-wide CRISPR/Cas screen	584:614	a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity	584:692	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	9	84	theme	TRPC6	1744:1748	arg1	sites					1766:1770	the two TRPC6 N-glycosylation sites	1736:1770	the two TRPC6 N-glycosylation sites	1736:1770	However, mutating the two TRPC6 N-glycosylation sites abrogated the cytotoxicity of mutant TRPC6 and reduced its surface expression.
31266804	4	85	theme	membrane	807:814	arg1	insertase					846:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase	776:854	Exploiting this phenotype in a genome-wide CRISPR/Cas screen for genes whose inactivation rescues cells from TRPC6-associated cytotoxicity, we identified several proteins essential for TRPC6 protein expression, including the endoplasmic reticulum (ER) membrane protein complex transmembrane insertase.
31266804	3	86	theme	channel	506:512	arg1	variants					514:521	gain-of-function TRPC6 channel variants	483:521	gain-of-function TRPC6 channel variants	483:521	Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in cultured cells.
31266804	5	87	theme	channels	1080:1087	arg1	expression					1038:1047	expression	1038:1047	expression of TRPC6 and several other ion channels and transporters	1038:1104	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	7	88	theme	protein	1355:1361	arg1	glycosylation					1363:1375	N-linked protein glycosylation	1346:1375	N-linked protein glycosylation	1346:1375	Additionally enriched among the screen hits were genes involved in N-linked protein glycosylation.
31266804	10	89	theme	multiple	2010:2017	arg1	roles					2019:2023	multiple roles	2010:2023	multiple roles	2010:2023	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	8	90	theme	necessary	1472:1480	arg1	MGAT1					1464:1468	MGAT1	1464:1468	MGAT1	1464:1468	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	8	90	theme	necessary	1472:1480	arg1	β-1,2-N-acetylglucosaminyltransferase					1425:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	1390:1461	the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	1390:1469	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	3	91	theme	gain-of-function	483:498	arg1	variants					514:521	gain-of-function TRPC6 channel variants	483:521	gain-of-function TRPC6 channel variants	483:521	Here, we found that overexpression of gain-of-function TRPC6 channel variants is cytotoxic in cultured cells.
31266804	6	92	theme	opposite	1206:1213	arg1	strand					1215:1220	83 opposite strand	1203:1220	the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS)	1155:1230	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	1	93	theme	potential	164:172	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	93	theme	potential	164:172	arg1	TRPC6					211:215	TRPC6	211:215	TRPC6	211:215	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	93	theme	potential	164:172	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	9	94	theme	N-glycosylation	1750:1764	arg1	sites					1766:1770	the two TRPC6 N-glycosylation sites	1736:1770	the two TRPC6 N-glycosylation sites	1736:1770	However, mutating the two TRPC6 N-glycosylation sites abrogated the cytotoxicity of mutant TRPC6 and reduced its surface expression.
31266804	6	95	theme	domain	1196:1201	arg1	loss					1147:1150	loss	1147:1150	loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208	1147:1276	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	10	96	theme	channel	2039:2045	arg1	trafficking					2047:2057	channel trafficking	2039:2057	channel trafficking	2039:2057	These results expand the targets of TMEM208-mediated ER translocation to include multipass transmembrane proteins and suggest that TRPC6 N-glycosylation plays multiple roles in modulating channel trafficking and activity.
31266804	2	97	theme	segmental	338:346	arg1	glomerulosclerosis					348:365	autosomal-dominant focal segmental glomerulosclerosis	313:365	autosomal-dominant focal segmental glomerulosclerosis	313:365	Gain-of-function mutations in the human TRPC6 channel cause autosomal-dominant focal segmental glomerulosclerosis, but the molecular components involved in disease development remain unclear.
31266804	5	98	theme	other	1070:1074	arg1	channels					1080:1087	several other ion channels	1062:1087	several other ion channels	1062:1087	We also identified transmembrane protein 208 (TMEM208), a putative component of a signal recognition particle-independent (SND) ER protein-targeting pathway, as being necessary for expression of TRPC6 and several other ion channels and transporters.
31266804	6	99	theme	WD	1186:1187	arg1	WDR83OS					1223:1229	WDR83OS	1223:1229	WDR83OS	1223:1229	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	6	99	theme	WD	1186:1187	arg1	domain					1196:1201	the previously uncharacterized WD repeat domain	1155:1201	the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS)	1155:1230	TRPC6 expression was also diminished by loss of the previously uncharacterized WD repeat domain 83 opposite strand (WDR83OS), which interacted with both TRPC6 and TMEM208.
31266804	8	100	theme	N-linked	1512:1519	arg1	glycans					1521:1527	complex N-linked glycans	1504:1527	complex N-linked glycans	1504:1527	Deletion of the mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), necessary for the generation of complex N-linked glycans, abrogated TRPC6 gain-of-function variant-mediated Ca2+ influx and extracellular signal-regulated kinase activation in HEK cells, but failed to diminish cytotoxicity in cultured podocytes.
31266804	1	101	theme	ion	240:242	arg1	member					201:206	Transient receptor potential cation channel subfamily C member 6	145:208	Transient receptor potential cation channel subfamily C member 6 (TRPC6)	145:216	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
31266804	1	101	theme	ion	240:242	arg1	channel					244:250	a widely expressed ion channel	221:250	a widely expressed ion channel	221:250	Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a widely expressed ion channel.
30153553	4	0	theme	glycosides	611:620	arg1	acceptor					649:656	a glycosyl acceptor	638:656	a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides	638:717	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	4	0	theme	glycosides	611:620	arg1	One					583:585	One	583:585	One	583:585	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	4	0	theme	glycosides	611:620	arg1	glycosides					611:620	the 2-deoxy-β-C-aryl glycosides	590:620	the 2-deoxy-β-C-aryl glycosides	590:620	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	4	1	theme	O-linked	696:703	arg1	disaccharides					705:717	an O-linked disaccharides	693:717	an O-linked disaccharides	693:717	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	1	2	theme	Prins	336:340	arg1	cyclization					342:352	the Prins cyclization	332:352	the Prins cyclization	332:352	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	2	3	theme	salient	359:365	arg1	features					367:374	The salient features	355:374	The salient features of this methodology	355:394	The salient features of this methodology are high yields and excellent stereoselectivity.
30153553	2	3	theme	salient	359:365	arg1	yields					405:410	high yields	400:410	high yields	400:410	The salient features of this methodology are high yields and excellent stereoselectivity.
30153553	3	4	theme	protected	524:532	arg1	glycosides					551:560	differently protected 2-deoxy-β-C-aryl glycosides	512:560	differently protected 2-deoxy-β-C-aryl glycosides	512:560	This method has also been successfully applied to the synthesis of differently protected 2-deoxy-β-C-aryl glycosides and C-disaccharides.
30153553	0	5	theme	C-disaccharides	120:134	arg1	synthesis					107:115	the synthesis	103:115	the synthesis of C-disaccharides and differently protected C-aryl glycosides	103:178	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	4	6	theme	2-deoxy-β-C-aryl	594:609	arg1	glycosides					611:620	the 2-deoxy-β-C-aryl glycosides	590:620	the 2-deoxy-β-C-aryl glycosides	590:620	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	3	7	theme	2-deoxy-β-C-aryl	534:549	arg1	glycosides					551:560	differently protected 2-deoxy-β-C-aryl glycosides	512:560	differently protected 2-deoxy-β-C-aryl glycosides	512:560	This method has also been successfully applied to the synthesis of differently protected 2-deoxy-β-C-aryl glycosides and C-disaccharides.
30153553	4	8	used	utilized	626:633	arg2	One					583:585	One	583:585	One	583:585	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	4	8	used	utilized	626:633	arg2	glycosides					611:620	the 2-deoxy-β-C-aryl glycosides	590:620	the 2-deoxy-β-C-aryl glycosides	590:620	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	4	8	used	utilized	626:633	arg2	acceptor					649:656	a glycosyl acceptor	638:656	a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides	638:717	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	1	9	theme	di-O-pivaloyl	237:249	arg1	alcohol					273:279	di-O-pivaloyl protected homoallylic alcohol	237:279	di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization	237:352	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	0	10	theme	Stereoselective	0:14	arg1	synthesis					16:24	Stereoselective synthesis	0:24	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.	0:179	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	4	11	from	acceptor	649:656	arg1	glycosylation					665:677	the glycosylation to synthesize an O-linked disaccharides	661:717	the glycosylation to synthesize an O-linked disaccharides	661:717	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	2	12	theme	methodology	384:394	arg1	features					367:374	The salient features	355:374	The salient features of this methodology	355:394	The salient features of this methodology are high yields and excellent stereoselectivity.
30153553	2	12	theme	methodology	384:394	arg1	yields					405:410	high yields	400:410	high yields	400:410	The salient features of this methodology are high yields and excellent stereoselectivity.
30153553	1	13	theme	protected	251:259	arg1	alcohol					273:279	di-O-pivaloyl protected homoallylic alcohol	237:279	di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization	237:352	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	0	14	theme	2-deoxy-β-C-aryl/alkyl	29:50	arg1	glycosides					52:61	2-deoxy-β-C-aryl/alkyl glycosides	29:61	2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization	29:85	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	0	15	theme	protected	152:160	arg1	glycosides					169:178	differently protected C-aryl glycosides	140:178	differently protected C-aryl glycosides	140:178	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	1	16	theme	homoallylic	261:271	arg1	alcohol					273:279	di-O-pivaloyl protected homoallylic alcohol	237:279	di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization	237:352	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	0	17	theme	glycosides	169:178	arg1	synthesis					107:115	the synthesis	103:115	the synthesis of C-disaccharides and differently protected C-aryl glycosides	103:178	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	3	18	theme	glycosides	551:560	arg1	synthesis					499:507	the synthesis	495:507	the synthesis of differently protected 2-deoxy-β-C-aryl glycosides and C-disaccharides	495:580	This method has also been successfully applied to the synthesis of differently protected 2-deoxy-β-C-aryl glycosides and C-disaccharides.
30153553	0	19	theme	glycosides	52:61	arg1	synthesis					16:24	Stereoselective synthesis	0:24	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.	0:179	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	4	20	theme	glycosyl	640:647	arg1	acceptor					649:656	a glycosyl acceptor	638:656	a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides	638:717	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	4	20	theme	glycosyl	640:647	arg1	One					583:585	One	583:585	One	583:585	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	4	20	theme	glycosyl	640:647	arg1	glycosides					611:620	the 2-deoxy-β-C-aryl glycosides	590:620	the 2-deoxy-β-C-aryl glycosides	590:620	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	0	21	theme	C-aryl	162:167	arg1	glycosides					169:178	differently protected C-aryl glycosides	140:178	differently protected C-aryl glycosides	140:178	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	0	22	from	Application	88:98	arg1	synthesis					107:115	the synthesis	103:115	the synthesis of C-disaccharides and differently protected C-aryl glycosides	103:178	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	2	23	theme	excellent	416:424	arg1	stereoselectivity					426:442	excellent stereoselectivity	416:442	excellent stereoselectivity	416:442	The salient features of this methodology are high yields and excellent stereoselectivity.
30153553	0	24	theme	Prins	69:73	arg1	cyclization					75:85	Prins cyclization	69:85	Prins cyclization	69:85	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	4	25	link	O-linked	696:703	arg1	disaccharides					705:717	an O-linked disaccharides	693:717	an O-linked disaccharides	693:717	One of the 2-deoxy-β-C-aryl glycosides was utilized as a glycosyl acceptor in the glycosylation to synthesize an O-linked disaccharides.
30153553	2	26	theme	high	400:403	arg1	features					367:374	The salient features	355:374	The salient features of this methodology	355:394	The salient features of this methodology are high yields and excellent stereoselectivity.
30153553	2	26	theme	high	400:403	arg1	yields					405:410	high yields	400:410	high yields	400:410	The salient features of this methodology are high yields and excellent stereoselectivity.
30153553	1	27	attach	derived	281:287	arg2	alcohol					273:279	di-O-pivaloyl protected homoallylic alcohol	237:279	di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization	237:352	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	1	27	attach	derived	281:287	arg1	D-mannitol					294:303	D-mannitol	294:303	D-mannitol with various aldehydes via the Prins cyclization	294:352	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	0	28	dep	synthesis	16:24	arg1	Application					88:98	Application	88:98	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.	0:179	Stereoselective synthesis of 2-deoxy-β-C-aryl/alkyl glycosides using Prins cyclization: Application in the synthesis of C-disaccharides and differently protected C-aryl glycosides.
30153553	3	29	theme	C-disaccharides	566:580	arg1	synthesis					499:507	the synthesis	495:507	the synthesis of differently protected 2-deoxy-β-C-aryl glycosides and C-disaccharides	495:580	This method has also been successfully applied to the synthesis of differently protected 2-deoxy-β-C-aryl glycosides and C-disaccharides.
30153553	1	30	theme	various	310:316	arg1	aldehydes					318:326	various aldehydes	310:326	various aldehydes	310:326	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	1	31	with	D-mannitol	294:303	arg1	aldehydes					318:326	various aldehydes	310:326	various aldehydes	310:326	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
30153553	1	32	theme	2-Deoxy-β-C-aryl/alkyl	181:202	arg1	glycosides					204:213	2-Deoxy-β-C-aryl/alkyl glycosides	181:213	2-Deoxy-β-C-aryl/alkyl glycosides	181:213	2-Deoxy-β-C-aryl/alkyl glycosides were synthesized from di-O-pivaloyl protected homoallylic alcohol derived from D-mannitol with various aldehydes via the Prins cyclization.
29866804	3	0	from	individuals	398:408	arg1	isolates					373:380	oropharyngeal Neisseria meningitidis isolates	336:380	oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals	336:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	3	0	from	individuals	398:408	arg1	collection					322:331	a collection	320:331	a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals	320:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	5	1	theme	protein	606:612	arg1	glycosylation					614:626	O-linked protein glycosylation	597:626	O-linked protein glycosylation	597:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	3	2	theme	oropharyngeal	336:348	arg1	isolates					373:380	oropharyngeal Neisseria meningitidis isolates	336:380	oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals	336:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	5	3	theme	glycosylation	673:685	arg1	phenotypes					687:696	glycosylation phenotypes	673:696	glycosylation phenotypes	673:696	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	5	4	dep	predicting	508:517	arg1	i					505:505	i	505:505	i	505:505	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	4	5	theme	Paired	411:416	arg1	isolates					431:438	Paired longitudinal isolates	411:438	Paired longitudinal isolates from each individual	411:459	Paired longitudinal isolates from each individual were sequenced.
29866804	3	6	theme	collection	322:331	arg1	genomes					309:315	the genomes	305:315	the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals	305:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	1	7	theme	bacterial	85:93	arg1	sequencing					102:111	bacterial genome sequencing	85:111	bacterial genome sequencing	85:111	The affordability of bacterial genome sequencing has provided a helpful tool for sequencing large strain collections.
29866804	1	8	theme	genome	95:100	arg1	sequencing					102:111	bacterial genome sequencing	85:111	bacterial genome sequencing	85:111	The affordability of bacterial genome sequencing has provided a helpful tool for sequencing large strain collections.
29866804	5	9	theme	important	583:591	arg1	loci					558:561	phase-variable loci	543:561	phase-variable loci that encode enzymes important for O-linked protein glycosylation	543:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	5	9	theme	important	583:591	arg1	enzymes					575:581	enzymes	575:581	enzymes important for O-linked protein glycosylation	575:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	1	10	theme	sequencing	102:111	arg1	affordability					68:80	The affordability	64:80	The affordability of bacterial genome sequencing	64:111	The affordability of bacterial genome sequencing has provided a helpful tool for sequencing large strain collections.
29866804	0	11	theme	Phase-Variable	0:13	arg1	Genotypes					15:23	Phase-Variable Genotypes	0:23	Phase-Variable Genotypes	0:23	Phase-Variable Genotypes Sweetened by Glycosylation Phenotypes.
29866804	5	12	theme	specific	649:656	arg1	genotypes					658:666	specific genotypes	649:666	specific genotypes	649:666	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	5	13	theme	Genome	477:482	arg1	analyses					484:491	Genome analyses	477:491	Genome analyses	477:491	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	3	14	theme	meningitidis	360:371	arg1	isolates					373:380	oropharyngeal Neisseria meningitidis isolates	336:380	oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals	336:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	5	15	theme	O-linked	597:604	arg1	glycosylation					614:626	O-linked protein glycosylation	597:626	O-linked protein glycosylation	597:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	3	16	theme	isolates	373:380	arg1	collection					322:331	a collection	320:331	a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals	320:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	3	17	from	collection	322:331	arg1	individuals					398:408	50 healthy individuals	387:408	50 healthy individuals	387:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	5	18	dep	correlating	637:647	arg1	ii					633:634	ii	633:634	ii	633:634	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	0	19	theme	Glycosylation	38:50	arg1	Phenotypes					52:61	Glycosylation Phenotypes	38:61	Glycosylation Phenotypes	38:61	Phase-Variable Genotypes Sweetened by Glycosylation Phenotypes.
29866804	4	20	from	individual	450:459	arg1	isolates					431:438	Paired longitudinal isolates	411:438	Paired longitudinal isolates from each individual	411:459	Paired longitudinal isolates from each individual were sequenced.
29866804	5	21	theme	phase-variable	543:556	arg1	loci					558:561	phase-variable loci	543:561	phase-variable loci that encode enzymes important for O-linked protein glycosylation	543:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	5	21	theme	phase-variable	543:556	arg1	enzymes					575:581	enzymes	575:581	enzymes important for O-linked protein glycosylation	575:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	3	22	theme	healthy	390:396	arg1	individuals					398:408	50 healthy individuals	387:408	50 healthy individuals	387:408	200:e00794-17, 2018, https://doi.org/doi:10.1128/JB.00794-17) recently led an effort to analyze the genomes of a collection of oropharyngeal Neisseria meningitidis isolates from 50 healthy individuals.
29866804	5	23	theme	loci	558:561	arg1	state					534:538	the expression state	519:538	the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation	519:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	1	24	theme	helpful	128:134	arg1	tool					136:139	a helpful tool	126:139	a helpful tool for sequencing large strain collections	126:179	The affordability of bacterial genome sequencing has provided a helpful tool for sequencing large strain collections.
29866804	4	25	theme	longitudinal	418:429	arg1	isolates					431:438	Paired longitudinal isolates	411:438	Paired longitudinal isolates from each individual	411:459	Paired longitudinal isolates from each individual were sequenced.
29866804	1	26	theme	sequencing	145:154	arg1	collections					169:179	sequencing large strain collections	145:179	sequencing large strain collections	145:179	The affordability of bacterial genome sequencing has provided a helpful tool for sequencing large strain collections.
29866804	2	27	dep	Bacteriol	198:206	arg1	Bente					182:186	Bente	182:186	Bente	182:186	Bente Børud (J. Bacteriol.
29866804	5	28	theme	expression	523:532	arg1	state					534:538	the expression state	519:538	the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation	519:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29866804	1	29	theme	large	156:160	arg1	collections					169:179	sequencing large strain collections	145:179	sequencing large strain collections	145:179	The affordability of bacterial genome sequencing has provided a helpful tool for sequencing large strain collections.
29866804	1	30	theme	strain	162:167	arg1	collections					169:179	sequencing large strain collections	145:179	sequencing large strain collections	145:179	The affordability of bacterial genome sequencing has provided a helpful tool for sequencing large strain collections.
29866804	5	31	link	O-linked	597:604	arg1	glycosylation					614:626	O-linked protein glycosylation	597:626	O-linked protein glycosylation	597:626	Genome analyses focused on (i) predicting the expression state of phase-variable loci that encode enzymes important for O-linked protein glycosylation and (ii) correlating specific genotypes with glycosylation phenotypes.
29244071	6	0	theme	fatty	1279:1283	arg1	metabolism					1290:1299	glucose and fatty acid metabolism	1267:1299	metabolism	1290:1299	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	2	1	theme	stress	375:380	arg1	resistance					382:391	cellular stress resistance	366:391	cellular stress resistance	366:391	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	7	2	theme	ENHO	1406:1409	arg1	expression					1411:1420	endometrial EOGT and ENHO expression	1385:1420	endometrial EOGT and ENHO expression	1385:1420	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	8	3	theme	decidual	1527:1534	arg1	cells					1536:1540	decidual cells	1527:1540	decidual cells	1527:1540	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	2	4	theme	cellular	366:373	arg1	resistance					382:391	cellular stress resistance	366:391	cellular stress resistance	366:391	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	6	5	theme	decidualizing	1118:1130	arg1	cells					1132:1136	decidualizing cells	1118:1136	decidualizing cells	1118:1136	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	5	6	theme	decidual	1011:1018	arg1	genes					1020:1024	decidual genes	1011:1024	decidual genes involved in multiple cellular functions	1011:1064	Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions.
29244071	1	7	from	critical	170:177	arg1	pregnancy					97:105	pregnancy	97:105	pregnancy	97:105	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	4	8	theme	O-linked	783:790	arg1	OGT					853:855	an endoplasmic reticulum-specific OGT	819:855	an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins	819:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	8	theme	O-linked	783:790	arg1	EOGT					812:815	EOGT	812:815	EOGT	812:815	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	8	theme	O-linked	783:790	arg1	transferase					799:809	O-linked GlcNAc transferase	783:809	epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT)	743:816	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	9	theme	growth	753:758	arg1	factor					760:765	epidermal growth factor	743:765	epidermal growth factor	743:765	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	3	10	theme	primary	427:433	arg1	EnSCs					462:466	EnSCs	462:466	EnSCs	462:466	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	10	theme	primary	427:433	arg1	cells					455:459	primary endometrial stromal cells	427:459	primary endometrial stromal cells (EnSCs)	427:467	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	4	11	theme	secreted	891:898	arg1	number					881:886	a limited number	871:886	a limited number of secreted and membrane proteins	871:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	6	12	from	knockdown	1105:1113	arg1	cells					1132:1136	decidualizing cells	1118:1136	decidualizing cells	1118:1136	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	3	13	theme	β-N-acetylglucosamine	517:537	arg1	proteins					559:566	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	1	14	theme	conceptus	262:270	arg1	extension					235:243	extension	235:243	extension	235:243	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	1	14	theme	conceptus	262:270	arg1	survival					246:253	survival	246:253	survival of the conceptus	246:270	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	8	15	from	axis	1519:1522	arg1	cells					1536:1540	decidual cells	1527:1540	decidual cells	1527:1540	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	6	16	theme	acid	1285:1288	arg1	metabolism					1290:1299	glucose and fatty acid metabolism	1267:1299	metabolism	1290:1299	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	3	17	theme	‒modified	549:557	arg1	proteins					559:566	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	7	18	theme	endometrial	1385:1395	arg1	expression					1411:1420	endometrial EOGT and ENHO expression	1385:1420	endometrial EOGT and ENHO expression	1385:1420	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	0	19	from	Expression	47:56	arg1	Endometrium					81:91	Decidualizing Human Endometrium	61:91	Decidualizing Human Endometrium	61:91	The Glycosyltransferase EOGT Regulates Adropin Expression in Decidualizing Human Endometrium.
29244071	6	20	theme	energy	1146:1151	arg1	adropin					1203:1209	adropin	1203:1209	adropin	1203:1209	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	20	theme	energy	1146:1151	arg1	ENHO					1182:1185	ENHO	1182:1185	ENHO	1182:1185	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	20	theme	energy	1146:1151	arg1	gene					1090:1093	The most downregulated gene	1067:1093	The most downregulated gene upon EOGT knockdown in decidualizing cells	1067:1136	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	20	theme	energy	1146:1151	arg1	gene					1176:1179	the energy homeostasis-associated gene	1142:1179	the energy homeostasis-associated gene (ENHO)	1142:1186	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	4	21	theme	GlcNAc	792:797	arg1	OGT					853:855	an endoplasmic reticulum-specific OGT	819:855	an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins	819:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	21	theme	GlcNAc	792:797	arg1	EOGT					812:815	EOGT	812:815	EOGT	812:815	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	21	theme	GlcNAc	792:797	arg1	transferase					799:809	O-linked GlcNAc transferase	783:809	epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT)	743:816	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	6	22	theme	EOGT	1100:1103	arg1	knockdown					1105:1113	EOGT knockdown	1100:1113	EOGT knockdown in decidualizing cells	1100:1136	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	0	23	theme	Glycosyltransferase	4:22	arg1	EOGT					24:27	The Glycosyltransferase EOGT	0:27	The Glycosyltransferase EOGT	0:27	The Glycosyltransferase EOGT Regulates Adropin Expression in Decidualizing Human Endometrium.
29244071	4	24	theme	limited	873:879	arg1	number					881:886	a limited number	871:886	a limited number of secreted and membrane proteins	871:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	3	25	from	reduction	495:503	arg1	proteins					559:566	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	4	26	theme	epidermal	743:751	arg1	factor					760:765	epidermal growth factor	743:765	epidermal growth factor	743:765	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	27	theme	membrane	904:911	arg1	proteins					913:920	membrane proteins	904:920	membrane proteins	904:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	6	28	theme	glucose	1267:1273	arg1	metabolism					1290:1299	glucose and fatty acid metabolism	1267:1299	metabolism	1290:1299	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	8	29	from	points	1557:1562	arg1	turn					1552:1555	turn	1552:1555	turn	1552:1555	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	3	30	theme	enzyme	602:607	arg1	downregulation					580:593	downregulation	580:593	downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase)	580:731	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	7	31	theme	midluteal	1314:1322	arg1	biopsies					1336:1343	midluteal endometrial biopsies	1314:1343	midluteal endometrial biopsies	1314:1343	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	7	32	theme	inverse	1357:1363	arg1	correlation					1365:1375	an inverse correlation	1354:1375	an inverse correlation between endometrial EOGT and ENHO expression and body mass index	1354:1440	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	6	33	theme	metabolic	1214:1222	arg1	hormone					1224:1230	a metabolic hormone	1212:1230	a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism	1212:1299	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	33	theme	metabolic	1214:1222	arg1	adropin					1203:1209	adropin	1203:1209	adropin	1203:1209	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	2	34	theme	posttranslational	305:321	arg1	modification					323:334	an essential posttranslational modification	292:334	an essential posttranslational modification that links glucose sensing to cellular stress resistance	292:391	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	2	34	theme	posttranslational	305:321	arg1	O-GlcNAcylation					273:287	O-GlcNAcylation	273:287	O-GlcNAcylation	273:287	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	4	35	theme	endoplasmic	822:832	arg1	transferase					799:809	O-linked GlcNAc transferase	783:809	epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT)	743:816	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	35	theme	endoplasmic	822:832	arg1	OGT					853:855	an endoplasmic reticulum-specific OGT	819:855	an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins	819:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	6	36	theme	downregulated	1076:1088	arg1	gene					1090:1093	The most downregulated gene	1067:1093	The most downregulated gene upon EOGT knockdown in decidualizing cells	1067:1136	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	36	theme	downregulated	1076:1088	arg1	gene					1176:1179	the energy homeostasis-associated gene	1142:1179	the energy homeostasis-associated gene (ENHO)	1142:1186	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	8	37	theme	metabolic	1598:1606	arg1	disorders					1608:1616	metabolic disorders	1598:1616	metabolic disorders	1598:1616	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	2	38	theme	essential	295:303	arg1	modification					323:334	an essential posttranslational modification	292:334	an essential posttranslational modification that links glucose sensing to cellular stress resistance	292:391	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	2	38	theme	essential	295:303	arg1	O-GlcNAcylation					273:287	O-GlcNAcylation	273:287	O-GlcNAcylation	273:287	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	1	39	theme	fetomaternal	204:215	arg1	interface					217:225	the fetomaternal interface	200:225	the fetomaternal interface	200:225	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	3	40	theme	stromal	447:453	arg1	EnSCs					462:466	EnSCs	462:466	EnSCs	462:466	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	40	theme	stromal	447:453	arg1	cells					455:459	primary endometrial stromal cells	427:459	primary endometrial stromal cells (EnSCs)	427:467	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	41	theme	O-linked	508:515	arg1	O-GlcNAc					540:547	O-GlcNAc	540:547	O-GlcNAc	540:547	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	41	theme	O-linked	508:515	arg1	β-N-acetylglucosamine					517:537	O-linked β-N-acetylglucosamine	508:537	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	4	42	theme	differentiating	947:961	arg1	EnSCs					963:967	differentiating EnSCs	947:967	differentiating EnSCs	947:967	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	6	43	theme	homeostasis-associated	1153:1174	arg1	adropin					1203:1209	adropin	1203:1209	adropin	1203:1209	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	43	theme	homeostasis-associated	1153:1174	arg1	ENHO					1182:1185	ENHO	1182:1185	ENHO	1182:1185	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	43	theme	homeostasis-associated	1153:1174	arg1	gene					1090:1093	The most downregulated gene	1067:1093	The most downregulated gene upon EOGT knockdown in decidualizing cells	1067:1136	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	6	43	theme	homeostasis-associated	1153:1174	arg1	gene					1176:1179	the energy homeostasis-associated gene	1142:1179	the energy homeostasis-associated gene (ENHO)	1142:1186	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	4	44	link	O-linked	783:790	arg1	OGT					853:855	an endoplasmic reticulum-specific OGT	819:855	an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins	819:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	44	link	O-linked	783:790	arg1	EOGT					812:815	EOGT	812:815	EOGT	812:815	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	44	link	O-linked	783:790	arg1	transferase					799:809	O-linked GlcNAc transferase	783:809	epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT)	743:816	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	1	45	theme	interface	217:225	arg1	integrity					187:195	the integrity	183:195	the integrity of the fetomaternal interface	183:225	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	0	46	theme	Adropin	39:45	arg1	Expression					47:56	Adropin Expression	39:56	Adropin Expression in Decidualizing Human Endometrium	39:91	The Glycosyltransferase EOGT Regulates Adropin Expression in Decidualizing Human Endometrium.
29244071	3	47	theme	cells	455:459	arg1	decidualization					408:422	decidualization	408:422	decidualization of primary endometrial stromal cells (EnSCs)	408:467	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	4	48	theme	domain-specific	767:781	arg1	OGT					853:855	an endoplasmic reticulum-specific OGT	819:855	an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins	819:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	48	theme	domain-specific	767:781	arg1	EOGT					812:815	EOGT	812:815	EOGT	812:815	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	48	theme	domain-specific	767:781	arg1	transferase					799:809	O-linked GlcNAc transferase	783:809	epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT)	743:816	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	5	49	theme	multiple	1038:1045	arg1	functions					1056:1064	multiple cellular functions	1038:1064	multiple cellular functions	1038:1064	Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions.
29244071	3	50	dep	transferase	652:662	arg1	OGT					665:667	OGT	665:667	O-GlcNAc transferase; OGT	643:667	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	0	51	theme	Decidualizing	61:73	arg1	Endometrium					81:91	Decidualizing Human Endometrium	61:91	Decidualizing Human Endometrium	61:91	The Glycosyltransferase EOGT Regulates Adropin Expression in Decidualizing Human Endometrium.
29244071	4	52	theme	proteins	913:920	arg1	number					881:886	a limited number	871:886	a limited number of secreted and membrane proteins	871:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	8	53	theme	mechanistic	1573:1583	arg1	link					1585:1588	a mechanistic link	1571:1588	a mechanistic link between metabolic disorders and adverse pregnancy outcome	1571:1646	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	5	54	theme	cellular	1047:1054	arg1	functions					1056:1064	multiple cellular functions	1038:1064	multiple cellular functions	1038:1064	Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions.
29244071	2	55	attach	links	341:345	arg2	modification					323:334	an essential posttranslational modification	292:334	an essential posttranslational modification that links glucose sensing to cellular stress resistance	292:391	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	2	55	attach	links	341:345	arg1	resistance					382:391	cellular stress resistance	366:391	cellular stress resistance	366:391	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	2	55	attach	links	341:345	arg2	O-GlcNAcylation					273:287	O-GlcNAcylation	273:287	O-GlcNAcylation	273:287	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	1	56	theme	endometrial	122:132	arg1	cells					143:147	endometrial decidual cells	122:147	endometrial decidual cells	122:147	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	3	57	theme	endometrial	435:445	arg1	EnSCs					462:466	EnSCs	462:466	EnSCs	462:466	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	57	theme	endometrial	435:445	arg1	cells					455:459	primary endometrial stromal cells	427:459	primary endometrial stromal cells (EnSCs)	427:467	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	8	58	theme	pregnancy	1630:1638	arg1	outcome					1640:1646	adverse pregnancy outcome	1622:1646	adverse pregnancy outcome	1622:1646	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	3	59	theme	%	493:493	arg1	reduction					495:503	a 60% reduction	489:503	a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	489:566	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	60	theme	enzyme	682:687	arg1	downregulation					580:593	downregulation	580:593	downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase)	580:731	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	4	61	theme	reticulum-specific	834:851	arg1	transferase					799:809	O-linked GlcNAc transferase	783:809	epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT)	743:816	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	4	61	theme	reticulum-specific	834:851	arg1	OGT					853:855	an endoplasmic reticulum-specific OGT	819:855	an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins	819:920	Notably, epidermal growth factor domain-specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs.
29244071	1	62	theme	decidual	134:141	arg1	cells					143:147	endometrial decidual cells	122:147	endometrial decidual cells	122:147	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	8	63	theme	adverse	1622:1628	arg1	outcome					1640:1646	adverse pregnancy outcome	1622:1646	adverse pregnancy outcome	1622:1646	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	8	64	theme	EOGT-adropin	1506:1517	arg1	axis					1519:1522	the EOGT-adropin axis	1502:1522	the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome	1502:1646	Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.
29244071	3	65	theme	O-GlcNAc	643:650	arg1	substrates					631:640	substrates	631:640	substrates (O-GlcNAc transferase; OGT)	631:668	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	65	theme	O-GlcNAc	643:650	arg1	transferase					652:662	O-GlcNAc transferase	643:662	O-GlcNAc transferase; OGT	643:667	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	7	66	theme	mass	1431:1434	arg1	index					1436:1440	body mass index	1426:1440	body mass index	1426:1440	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	1	67	theme	cells	143:147	arg1	resistance					108:117	resistance	108:117	resistance of endometrial decidual cells to stress signals	108:165	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	3	68	link	O-linked	508:515	arg1	O-GlcNAc					540:547	O-GlcNAc	540:547	O-GlcNAc	540:547	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	3	68	link	O-linked	508:515	arg1	β-N-acetylglucosamine					517:537	O-linked β-N-acetylglucosamine	508:537	O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins	508:566	Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked β-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase).
29244071	6	69	theme	energy	1244:1249	arg1	homeostasis					1251:1261	energy homeostasis	1244:1261	energy homeostasis	1244:1261	The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis-associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism.
29244071	5	70	theme	EOGT	983:986	arg1	Knockdown					970:978	Knockdown	970:978	Knockdown of EOGT	970:986	Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions.
29244071	7	71	theme	body	1426:1429	arg1	index					1436:1440	body mass index	1426:1440	body mass index	1426:1440	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	1	72	from	pregnancy	97:105	arg1	critical					170:177	critical	170:177	critical	170:177	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	2	73	theme	glucose	347:353	arg1	sensing					355:361	glucose sensing	347:361	glucose sensing	347:361	O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance.
29244071	7	74	theme	endometrial	1324:1334	arg1	biopsies					1336:1343	midluteal endometrial biopsies	1314:1343	midluteal endometrial biopsies	1314:1343	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	5	75	theme	genes	1020:1024	arg1	network					1000:1006	a network	998:1006	a network of decidual genes involved in multiple cellular functions	998:1064	Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions.
29244071	7	76	theme	biopsies	1336:1343	arg1	Analysis					1302:1309	Analysis	1302:1309	Analysis of midluteal endometrial biopsies	1302:1343	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29244071	1	77	theme	stress	152:157	arg1	signals					159:165	stress signals	152:165	stress signals	152:165	In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus.
29244071	0	78	theme	Human	75:79	arg1	Endometrium					81:91	Decidualizing Human Endometrium	61:91	Decidualizing Human Endometrium	61:91	The Glycosyltransferase EOGT Regulates Adropin Expression in Decidualizing Human Endometrium.
29244071	7	79	theme	EOGT	1397:1400	arg1	expression					1411:1420	endometrial EOGT and ENHO expression	1385:1420	endometrial EOGT and ENHO expression	1385:1420	Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index.
29753090	5	0	theme	protein	710:716	arg1	capability					733:742	protein identification capability	710:742	protein identification capability using proteomic approaches	710:769	However, this enrichment results in a loss of protein identification capability using proteomic approaches.
29753090	0	1	from	separation	8:17	arg1	glands					75:80	mouse submandibular glands	55:80	mouse submandibular glands	55:80	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	3	2	theme	matrix	472:477	arg1	electrophoresis					479:493	molecular matrix electrophoresis	462:493	a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins	450:547	In 2009, we published a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins.
29753090	3	2	theme	matrix	472:477	arg1	SMME					496:499	SMME	496:499	SMME	496:499	In 2009, we published a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins.
29753090	9	3	theme	anti-MUC10	1244:1253	arg1	antibody					1255:1262	anti-MUC10 antibody	1244:1262	anti-MUC10 antibody	1244:1262	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	5	4	theme	identification	718:731	arg1	capability					733:742	protein identification capability	710:742	protein identification capability using proteomic approaches	710:769	However, this enrichment results in a loss of protein identification capability using proteomic approaches.
29753090	11	5	theme	unknown	1473:1479	arg1	molecule					1492:1499	an unknown mucin-like molecule	1470:1499	an unknown mucin-like molecule	1470:1499	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	1	6	theme	high	175:178	arg1	mass					190:193	high molecular mass	175:193	high molecular mass	175:193	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	11	7	theme	young	1449:1453	arg1	mice					1455:1458	young mice	1449:1458	young mice	1449:1458	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	9	8	theme	proteomic	1167:1175	arg1	analysis					1177:1184	proteomic analysis	1167:1184	proteomic analysis of the band on the SMME membrane	1167:1217	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	0	9	theme	molecular	95:103	arg1	electrophoresis					112:126	molecular matrix electrophoresis	95:126	molecular matrix electrophoresis	95:126	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	4	10	theme	100 KDa	641:647	arg1	filter					656:661	a 100 KDa cutoff filter	639:661	a 100 KDa cutoff filter	639:661	For SMME analysis, mucins have been enriched by ultrafiltration of trypsin digests using a 100 KDa cutoff filter.
29753090	2	11	theme	separation	288:297	arg1	method					299:304	easy separation method	283:304	easy separation method	283:304	As easy separation method, such as gel electrophoresis, however, does not exist for mucins, due to their large molecular sizes and heterogeneities.
29753090	4	12	theme	SMME	554:557	arg1	analysis					559:566	SMME analysis	554:566	SMME analysis	554:566	For SMME analysis, mucins have been enriched by ultrafiltration of trypsin digests using a 100 KDa cutoff filter.
29753090	9	13	from	band	1193:1196	arg1	membrane					1210:1217	the SMME membrane	1201:1217	the SMME membrane	1201:1217	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	6	14	theme	SMME	856:859	arg1	analysis					861:868	SMME analysis	856:868	SMME analysis	856:868	In this study, we describe a simple enrichment of mucins without trypsinization for SMME analysis.
29753090	1	15	with	proteins	161:168	arg1	mass					190:193	high molecular mass	175:193	high molecular mass	175:193	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	7	16	theme	porcine	908:914	arg1	gland					930:934	a porcine submandibular gland	906:934	a porcine submandibular gland	906:934	The enrichment was developed using a porcine submandibular gland and then was applied to study and compare mouse submandibular glands between young and aged mice.
29753090	2	17	theme	easy	283:286	arg1	method					299:304	easy separation method	283:304	easy separation method	283:304	As easy separation method, such as gel electrophoresis, however, does not exist for mucins, due to their large molecular sizes and heterogeneities.
29753090	4	18	theme	cutoff	649:654	arg1	filter					656:661	a 100 KDa cutoff filter	639:661	a 100 KDa cutoff filter	639:661	For SMME analysis, mucins have been enriched by ultrafiltration of trypsin digests using a 100 KDa cutoff filter.
29753090	7	19	theme	submandibular	916:928	arg1	gland					930:934	a porcine submandibular gland	906:934	a porcine submandibular gland	906:934	The enrichment was developed using a porcine submandibular gland and then was applied to study and compare mouse submandibular glands between young and aged mice.
29753090	1	20	theme	molecular	180:188	arg1	mass					190:193	high molecular mass	175:193	high molecular mass	175:193	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	0	21	theme	matrix	105:110	arg1	electrophoresis					112:126	molecular matrix electrophoresis	95:126	molecular matrix electrophoresis	95:126	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	9	22	from	immunostaining	1223:1236	arg1	membrane					1210:1217	the SMME membrane	1201:1217	the SMME membrane	1201:1217	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	0	23	theme	rapid	2:6	arg1	separation					8:17	A rapid separation	0:17	A rapid separation	0:17	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	0	24	from	characterization	23:38	arg1	glands					75:80	mouse submandibular glands	55:80	mouse submandibular glands	55:80	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	7	25	theme	young	1013:1017	arg1	mice					1028:1031	young and aged mice	1013:1031	young and aged mice	1013:1031	The enrichment was developed using a porcine submandibular gland and then was applied to study and compare mouse submandibular glands between young and aged mice.
29753090	4	26	theme	digests	625:631	arg1	ultrafiltration					598:612	ultrafiltration	598:612	ultrafiltration of trypsin digests using a 100 KDa cutoff filter	598:661	For SMME analysis, mucins have been enriched by ultrafiltration of trypsin digests using a 100 KDa cutoff filter.
29753090	9	27	theme	mucins	1133:1138	arg1	mucins					1133:1138	the mucins	1129:1138	the mucins	1129:1138	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	9	27	theme	mucins	1133:1138	arg1	MUC10					1158:1162	MUC10	1158:1162	MUC10	1158:1162	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	9	27	theme	mucins	1133:1138	arg1	One					1122:1124	One	1122:1124	One	1122:1124	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	8	28	theme	mouse	1039:1043	arg1	glands					1059:1064	mouse submandibular glands	1039:1064	mouse submandibular glands	1039:1064	From mouse submandibular glands, hyaluronic acid and some mucins were observed by SMME.
29753090	3	29	used	used	521:524	arg2	method					502:507	a supported molecular matrix electrophoresis (SMME) method	450:507	a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins	450:547	In 2009, we published a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins.
29753090	6	30	theme	mucins	822:827	arg1	enrichment					808:817	a simple enrichment	799:817	a simple enrichment of mucins without trypsinization for SMME analysis	799:868	In this study, we describe a simple enrichment of mucins without trypsinization for SMME analysis.
29753090	3	31	theme	electrophoresis	479:493	arg1	method					502:507	a supported molecular matrix electrophoresis (SMME) method	450:507	a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins	450:547	In 2009, we published a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins.
29753090	11	32	theme	molecules	1407:1415	arg1	lower					1422:1426	lower	1422:1426	lower	1422:1426	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	11	32	theme	molecules	1407:1415	arg1	concentrations					1383:1396	the concentrations	1379:1396	the concentrations of these molecules	1379:1415	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	2	33	theme	large	385:389	arg1	sizes					401:405	their large molecular sizes	379:405	their large molecular sizes	379:405	As easy separation method, such as gel electrophoresis, however, does not exist for mucins, due to their large molecular sizes and heterogeneities.
29753090	5	34	theme	capability	733:742	arg1	loss					702:705	a loss	700:705	a loss of protein identification capability using proteomic approaches	700:769	However, this enrichment results in a loss of protein identification capability using proteomic approaches.
29753090	0	35	from	glands	75:80	arg1	separation					8:17	A rapid separation	0:17	A rapid separation	0:17	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	0	35	from	glands	75:80	arg1	mucins					43:48	mucins	43:48	mucins from mouse submandibular glands	43:80	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	0	35	from	glands	75:80	arg1	characterization					23:38	characterization	23:38	characterization	23:38	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	11	36	theme	mucin-like	1481:1490	arg1	molecule					1492:1499	an unknown mucin-like molecule	1470:1499	an unknown mucin-like molecule	1470:1499	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	4	37	theme	trypsin	617:623	arg1	digests					625:631	trypsin digests	617:631	trypsin digests using a 100 KDa cutoff filter	617:661	For SMME analysis, mucins have been enriched by ultrafiltration of trypsin digests using a 100 KDa cutoff filter.
29753090	7	38	theme	aged	1023:1026	arg1	mice					1028:1031	young and aged mice	1013:1031	young and aged mice	1013:1031	The enrichment was developed using a porcine submandibular gland and then was applied to study and compare mouse submandibular glands between young and aged mice.
29753090	9	39	from	membrane	1210:1217	arg1	immunostaining					1223:1236	immunostaining	1223:1236	immunostaining using anti-MUC10 antibody	1223:1262	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	9	39	from	membrane	1210:1217	arg1	analysis					1177:1184	proteomic analysis	1167:1184	proteomic analysis of the band on the SMME membrane	1167:1217	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	10	40	theme	MUC10	1285:1289	arg1	NeuAcα2-3Galβ1-3GalNAc					1312:1333	NeuAcα2-3Galβ1-3GalNAc	1312:1333	NeuAcα2-3Galβ1-3GalNAc	1312:1333	A major O-glycan of MUC10 was determined to be NeuAcα2-3Galβ1-3GalNAc.
29753090	10	40	theme	MUC10	1285:1289	arg1	O-glycan					1273:1280	A major O-glycan	1265:1280	A major O-glycan of MUC10	1265:1289	A major O-glycan of MUC10 was determined to be NeuAcα2-3Galβ1-3GalNAc.
29753090	1	41	theme	various	216:222	arg1	infection					243:251	infection	243:251	infection	243:251	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	1	41	theme	various	216:222	arg1	diseases					224:231	various diseases	216:231	various diseases including infection, inflammation, and cancer	216:277	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	1	41	theme	various	216:222	arg1	inflammation					254:265	inflammation	254:265	inflammation	254:265	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	1	41	theme	various	216:222	arg1	cancer					272:277	cancer	272:277	cancer	272:277	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	5	42	theme	proteomic	750:758	arg1	approaches					760:769	proteomic approaches	750:769	proteomic approaches	750:769	However, this enrichment results in a loss of protein identification capability using proteomic approaches.
29753090	8	43	theme	hyaluronic	1067:1076	arg1	acid					1078:1081	hyaluronic acid	1067:1081	hyaluronic acid	1067:1081	From mouse submandibular glands, hyaluronic acid and some mucins were observed by SMME.
29753090	6	44	theme	simple	801:806	arg1	enrichment					808:817	a simple enrichment	799:817	a simple enrichment of mucins without trypsinization for SMME analysis	799:868	In this study, we describe a simple enrichment of mucins without trypsinization for SMME analysis.
29753090	7	45	theme	mouse	978:982	arg1	glands					998:1003	mouse submandibular glands	978:1003	mouse submandibular glands between young and aged mice	978:1031	The enrichment was developed using a porcine submandibular gland and then was applied to study and compare mouse submandibular glands between young and aged mice.
29753090	3	46	theme	supported	452:460	arg1	method					502:507	a supported molecular matrix electrophoresis (SMME) method	450:507	a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins	450:547	In 2009, we published a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins.
29753090	0	47	theme	mucins	43:48	arg1	separation					8:17	A rapid separation	0:17	A rapid separation	0:17	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	0	47	theme	mucins	43:48	arg1	characterization					23:38	characterization	23:38	characterization	23:38	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	1	48	gly	glycosylated	148:159	arg1	proteins					161:168	heavily glycosylated proteins	140:168	heavily glycosylated proteins with high molecular mass	140:193	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	1	48	gly	glycosylated	148:159	arg1	Mucins					129:134	Mucins	129:134	Mucins	129:134	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	9	49	theme	band	1193:1196	arg1	immunostaining					1223:1236	immunostaining	1223:1236	immunostaining using anti-MUC10 antibody	1223:1262	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	9	49	theme	band	1193:1196	arg1	analysis					1177:1184	proteomic analysis	1167:1184	proteomic analysis of the band on the SMME membrane	1167:1217	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	11	50	theme	aged	1528:1531	arg1	gland					1553:1557	the aged mouse submandibular gland	1524:1557	the aged mouse submandibular gland	1524:1557	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	3	51	theme	molecular	462:470	arg1	electrophoresis					479:493	molecular matrix electrophoresis	462:493	a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins	450:547	In 2009, we published a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins.
29753090	3	51	theme	molecular	462:470	arg1	SMME					496:499	SMME	496:499	SMME	496:499	In 2009, we published a supported molecular matrix electrophoresis (SMME) method that can be used to characterize mucins.
29753090	7	52	theme	submandibular	984:996	arg1	glands					998:1003	mouse submandibular glands	978:1003	mouse submandibular glands between young and aged mice	978:1031	The enrichment was developed using a porcine submandibular gland and then was applied to study and compare mouse submandibular glands between young and aged mice.
29753090	10	53	theme	major	1267:1271	arg1	NeuAcα2-3Galβ1-3GalNAc					1312:1333	NeuAcα2-3Galβ1-3GalNAc	1312:1333	NeuAcα2-3Galβ1-3GalNAc	1312:1333	A major O-glycan of MUC10 was determined to be NeuAcα2-3Galβ1-3GalNAc.
29753090	10	53	theme	major	1267:1271	arg1	O-glycan					1273:1280	A major O-glycan	1265:1280	A major O-glycan of MUC10	1265:1289	A major O-glycan of MUC10 was determined to be NeuAcα2-3Galβ1-3GalNAc.
29753090	9	54	from	analysis	1177:1184	arg1	membrane					1210:1217	the SMME membrane	1201:1217	the SMME membrane	1201:1217	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	2	55	theme	gel	315:317	arg1	electrophoresis					319:333	gel electrophoresis	315:333	gel electrophoresis	315:333	As easy separation method, such as gel electrophoresis, however, does not exist for mucins, due to their large molecular sizes and heterogeneities.
29753090	11	56	theme	aged	1431:1434	arg1	mice					1436:1439	aged mice	1431:1439	aged mice	1431:1439	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	0	57	theme	submandibular	61:73	arg1	glands					75:80	mouse submandibular glands	55:80	mouse submandibular glands	55:80	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	9	58	theme	SMME	1205:1208	arg1	membrane					1210:1217	the SMME membrane	1201:1217	the SMME membrane	1201:1217	One of the mucins was identified as MUC10 by proteomic analysis of the band on the SMME membrane and immunostaining using anti-MUC10 antibody.
29753090	2	59	theme	molecular	391:399	arg1	sizes					401:405	their large molecular sizes	379:405	their large molecular sizes	379:405	As easy separation method, such as gel electrophoresis, however, does not exist for mucins, due to their large molecular sizes and heterogeneities.
29753090	1	60	theme	glycosylated	148:159	arg1	proteins					161:168	heavily glycosylated proteins	140:168	heavily glycosylated proteins with high molecular mass	140:193	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	1	60	theme	glycosylated	148:159	arg1	Mucins					129:134	Mucins	129:134	Mucins	129:134	Mucins are heavily glycosylated proteins with high molecular mass, and are involved in various diseases including infection, inflammation, and cancer.
29753090	0	61	theme	mouse	55:59	arg1	glands					75:80	mouse submandibular glands	55:80	mouse submandibular glands	55:80	A rapid separation and characterization of mucins from mouse submandibular glands by supported molecular matrix electrophoresis.
29753090	11	62	theme	mouse	1533:1537	arg1	gland					1553:1557	the aged mouse submandibular gland	1524:1557	the aged mouse submandibular gland	1524:1557	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	11	63	theme	submandibular	1539:1551	arg1	gland					1553:1557	the aged mouse submandibular gland	1524:1557	the aged mouse submandibular gland	1524:1557	Furthermore, our experiments revealed that the concentrations of these molecules were lower in aged mice than in young mice, and that an unknown mucin-like molecule was detected only from the aged mouse submandibular gland.
29753090	8	64	theme	submandibular	1045:1057	arg1	glands					1059:1064	mouse submandibular glands	1039:1064	mouse submandibular glands	1039:1064	From mouse submandibular glands, hyaluronic acid and some mucins were observed by SMME.
31865461	8	0	theme	human	1526:1530	arg1	tract					1535:1539	the human GI tract	1522:1539	the human GI tract	1522:1539	This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
31865461	4	1	theme	prebiotic	631:639	arg1	activity					641:648	their prebiotic activity	625:648	their prebiotic activity	625:648	AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios.
31865461	1	2	theme	wheat	147:151	arg1	flour					153:157	wheat flour	147:157	wheat flour	147:157	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	7	3	from	ratios	1399:1404	arg1	flour					1415:1419	wheat flour	1409:1419	wheat flour which is major source of cereal fibre in the diet	1409:1469	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	6	4	theme	significant	947:957	arg1	activity					971:978	a significant bifidogenic activity	945:978	a significant bifidogenic activity	945:978	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
31865461	1	5	theme	flour	153:157	arg1	fraction					135:142	the non-starch polysaccharide (NSP) fraction	99:142	the non-starch polysaccharide (NSP) fraction of wheat flour	99:157	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	2	6	located	present	210:216	arg2	These					195:199	These	195:199	These	195:199	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	2	6	located	present	210:216	arg1	grains					234:239	other cereal grains	221:239	other cereal grains	221:239	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	8	7	from	population	1496:1505	arg1	tract					1535:1539	the human GI tract	1522:1539	the human GI tract	1522:1539	This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
31865461	5	8	dep	in	747:748	arg1	vitro					750:754	vitro	750:754	vitro	750:754	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	7	9	from	increases	1196:1204	arg1	bacteria					1215:1222	total bacteria	1209:1222	total bacteria	1209:1222	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	8	10	from	composition	1565:1575	arg1	diet					1597:1600	the diet	1593:1600	the diet	1593:1600	This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
31865461	4	11	theme	different	683:691	arg1	ratios					693:698	different ratios	683:698	different ratios	683:698	AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios.
31865461	7	12	theme	wheat	1409:1413	arg1	flour					1415:1419	wheat flour	1409:1419	wheat flour which is major source of cereal fibre in the diet	1409:1469	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	7	13	theme	increases	1196:1204	arg1	concentration					1163:1175	concentration	1163:1175	concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1163:1305	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	3	14	theme	major	479:483	arg1	foods					485:489	the major foods	475:489	the major foods consumed	475:498	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	3	15	theme	increased	514:522	arg1	activity					534:541	increased prebiotic activity	514:541	increased prebiotic activity	514:541	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	5	16	theme	fluorescence	860:871	arg1	Flow-FISH					896:904	Flow-FISH	896:904	Flow-FISH	896:904	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	5	16	theme	fluorescence	860:871	arg1	hybridisation					881:893	fluorescence in situ hybridisation	860:893	fluorescence in situ hybridisation (Flow-FISH)	860:905	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	2	17	from	component	293:301	arg1	rye					316:318	rye	316:318	rye	316:318	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	2	17	from	component	293:301	arg1	wheat					306:310	wheat	306:310	wheat	306:310	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	3	18	theme	present	464:470	arg1	ratios					457:462	the ratios	453:462	the ratios present in the major foods consumed	453:498	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	8	19	theme	fibre	1584:1588	arg1	composition					1565:1575	the composition	1561:1575	the composition of the fibre in the diet	1561:1600	This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
31865461	5	20	theme	bacterial	798:806	arg1	populations					808:818	bacterial populations	798:818	bacterial populations	798:818	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	7	21	from	source	1436:1441	arg1	diet					1466:1469	the diet	1462:1469	the diet	1462:1469	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	5	22	theme	in	747:748	arg1	fermentation					756:767	in vitro fermentation	747:767	in vitro fermentation	747:767	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	5	23	with	cytometry	845:853	arg1	Flow-FISH					896:904	Flow-FISH	896:904	Flow-FISH	896:904	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	5	23	with	cytometry	845:853	arg1	hybridisation					881:893	fluorescence in situ hybridisation	860:893	fluorescence in situ hybridisation (Flow-FISH)	860:905	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	1	24	theme	main	80:83	arg1	arabinoxylan					163:174	arabinoxylan	163:174	arabinoxylan (AX)	163:179	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	1	24	theme	main	80:83	arg1	components					85:94	The main components	76:94	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour	76:157	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	2	25	from	present	210:216	arg1	grains					234:239	other cereal grains	221:239	other cereal grains	221:239	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	4	26	theme	in	585:586	arg1	studies					607:613	in vitro fermentation studies	585:613	in vitro fermentation studies to assess their prebiotic activity when used individually	585:671	AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios.
31865461	0	27	theme	prebiotic	12:20	arg1	activity					22:29	Comparative prebiotic activity	0:29	Comparative prebiotic activity of mixtures of cereal grain polysaccharides	0:73	Comparative prebiotic activity of mixtures of cereal grain polysaccharides.
31865461	2	28	from	wheat	306:310	arg1	barley					336:341	barley	336:341	barley	336:341	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	2	28	from	wheat	306:310	arg1	oats					347:350	oats	347:350	oats	347:350	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	8	29	theme	GI	1532:1533	arg1	tract					1535:1539	the human GI tract	1522:1539	the human GI tract	1522:1539	This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
31865461	7	30	theme	greatest	1125:1132	arg1	activity					1144:1151	The greatest prebiotic activity	1121:1151	The greatest prebiotic activity	1121:1151	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	7	31	theme	coccoides/Eubacterium	1278:1298	arg1	groups					1300:1305	beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1235:1305	beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1235:1305	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	0	32	theme	Comparative	0:10	arg1	activity					22:29	Comparative prebiotic activity	0:29	Comparative prebiotic activity of mixtures of cereal grain polysaccharides	0:73	Comparative prebiotic activity of mixtures of cereal grain polysaccharides.
31865461	6	33	theme	prebiotic	1101:1109	arg1	activity					1111:1118	prebiotic activity	1101:1118	prebiotic activity	1101:1118	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
31865461	4	34	theme	fermentation	594:605	arg1	studies					607:613	in vitro fermentation studies	585:613	in vitro fermentation studies to assess their prebiotic activity when used individually	585:671	AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios.
31865461	6	35	theme	AX	924:925	arg1	Fermentation					908:919	Fermentation	908:919	Fermentation of AX	908:925	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
31865461	2	36	from	rye	316:318	arg1	barley					336:341	barley	336:341	barley	336:341	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	2	36	from	rye	316:318	arg1	oats					347:350	oats	347:350	oats	347:350	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	1	37	theme	non-starch	103:112	arg1	fraction					135:142	the non-starch polysaccharide (NSP) fraction	99:142	the non-starch polysaccharide (NSP) fraction of wheat flour	99:157	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	2	38	from	grains	234:239	arg1	present					210:216	present	210:216	present	210:216	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	6	39	theme	SCFAs	1012:1016	arg1	activity					971:978	a significant bifidogenic activity	945:978	a significant bifidogenic activity	945:978	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
31865461	6	39	theme	SCFAs	1012:1016	arg1	concentrations					994:1007	increased concentrations	984:1007	increased concentrations of SCFAs, mainly acetate	984:1032	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
31865461	8	40	theme	prebiotic	1619:1627	arg1	potential					1629:1637	the prebiotic potential	1615:1637	the prebiotic potential	1615:1637	This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
31865461	7	41	theme	prebiotic	1134:1142	arg1	activity					1144:1151	The greatest prebiotic activity	1121:1151	The greatest prebiotic activity	1121:1151	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	3	42	theme	prebiotic	524:532	arg1	activity					534:541	increased prebiotic activity	514:541	increased prebiotic activity	514:541	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	3	43	attach	present	464:470	arg2	ratios					457:462	the ratios	453:462	the ratios present in the major foods consumed	453:498	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	3	43	attach	present	464:470	arg1	foods					485:489	the major foods	475:489	the major foods consumed	475:498	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	7	44	theme	beneficial	1235:1244	arg1	groups					1300:1305	beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1235:1305	beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1235:1305	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	0	45	theme	mixtures	34:41	arg1	activity					22:29	Comparative prebiotic activity	0:29	Comparative prebiotic activity of mixtures of cereal grain polysaccharides	0:73	Comparative prebiotic activity of mixtures of cereal grain polysaccharides.
31865461	8	46	theme	bacteria	1510:1517	arg1	population					1496:1505	the population	1492:1505	the population of bacteria in the human GI tract	1492:1539	This indicates that the population of bacteria in the human GI tract may be modulated by the composition of the fibre in the diet, to maximise the prebiotic potential.
31865461	2	47	attach	present	210:216	arg2	These					195:199	These	195:199	These	195:199	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	2	47	attach	present	210:216	arg1	grains					234:239	other cereal grains	221:239	other cereal grains	221:239	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	7	48	theme	Bifidobacterium	1246:1260	arg1	groups					1300:1305	beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1235:1305	beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1235:1305	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	0	49	theme	grain	53:57	arg1	polysaccharides					59:73	cereal grain polysaccharides	46:73	cereal grain polysaccharides	46:73	Comparative prebiotic activity of mixtures of cereal grain polysaccharides.
31865461	5	50	theme	Short-chain	701:711	arg1	SCFAs					726:730	SCFAs	726:730	SCFAs	726:730	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	5	50	theme	Short-chain	701:711	arg1	fatty-acids					713:723	Short-chain fatty-acids	701:723	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation	701:767	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	2	51	from	β-glucan	324:331	arg1	barley					336:341	barley	336:341	barley	336:341	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	2	51	from	β-glucan	324:331	arg1	oats					347:350	oats	347:350	oats	347:350	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	1	52	theme	polysaccharide	114:127	arg1	fraction					135:142	the non-starch polysaccharide (NSP) fraction	99:142	the non-starch polysaccharide (NSP) fraction of wheat flour	99:157	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	0	53	theme	cereal	46:51	arg1	polysaccharides					59:73	cereal grain polysaccharides	46:73	cereal grain polysaccharides	46:73	Comparative prebiotic activity of mixtures of cereal grain polysaccharides.
31865461	7	54	theme	groups	1300:1305	arg1	concentration					1163:1175	concentration	1163:1175	concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1163:1305	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	7	55	theme	fibre	1453:1457	arg1	source					1436:1441	major source	1430:1441	major source of cereal fibre in the diet	1430:1469	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	1	56	dep	arabinoxylan	163:174	arg1	AX					177:178	AX	177:178	AX	177:178	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	5	57	theme	in	873:874	arg1	Flow-FISH					896:904	Flow-FISH	896:904	Flow-FISH	896:904	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	5	57	theme	in	873:874	arg1	hybridisation					881:893	fluorescence in situ hybridisation	860:893	fluorescence in situ hybridisation (Flow-FISH)	860:905	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	3	58	from	foods	485:489	arg1	present					464:470	present	464:470	present	464:470	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	7	59	theme	total	1209:1213	arg1	bacteria					1215:1222	total bacteria	1209:1222	total bacteria	1209:1222	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	7	60	from	concentration	1163:1175	arg1	bacteria					1215:1222	total bacteria	1209:1222	total bacteria	1209:1222	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	7	61	from	bacteria	1215:1222	arg1	concentration					1163:1175	concentration	1163:1175	concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1163:1305	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	4	62	dep	studies	607:613	arg1	assess					618:623	assess	618:623	to assess their prebiotic activity when used individually	615:671	AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios.
31865461	1	63	theme	NSP	130:132	arg1	fraction					135:142	the non-starch polysaccharide (NSP) fraction	99:142	the non-starch polysaccharide (NSP) fraction of wheat flour	99:157	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	6	64	theme	increased	984:992	arg1	concentrations					994:1007	increased concentrations	984:1007	increased concentrations of SCFAs, mainly acetate	984:1032	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
31865461	5	65	dep	in	873:874	arg1	situ					876:879	situ	876:879	situ	876:879	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	2	66	theme	cereal	227:232	arg1	grains					234:239	other cereal grains	221:239	other cereal grains	221:239	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	6	67	theme	fermentation	1051:1062	arg1	8-24 h					1041:1046	8-24 h	1041:1046	8-24 h of fermentation	1041:1062	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
31865461	7	68	theme	3:1	1361:1363	arg1	ratio					1365:1369	a 3:1 ratio	1359:1369	a 3:1 ratio	1359:1369	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	2	69	theme	major	287:291	arg1	component					293:301	the major component	283:301	the major component in wheat and rye and β-glucan in barley and oats	283:350	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	2	69	theme	major	287:291	arg1	AX					274:275	AX	274:275	AX	274:275	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	7	70	theme	total	1180:1184	arg1	SCFAs					1186:1190	total SCFAs	1180:1190	total SCFAs	1180:1190	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	7	71	from	SCFAs	1186:1190	arg1	bacteria					1215:1222	total bacteria	1209:1222	total bacteria	1209:1222	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	2	72	theme	other	221:225	arg1	grains					234:239	other cereal grains	221:239	other cereal grains	221:239	These are also present in other cereal grains, but their proportions vary with AX being the major component in wheat and rye and β-glucan in barley and oats.
31865461	7	73	from	groups	1300:1305	arg1	bacteria					1215:1222	total bacteria	1209:1222	total bacteria	1209:1222	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	1	74	theme	fraction	135:142	arg1	arabinoxylan					163:174	arabinoxylan	163:174	arabinoxylan (AX)	163:179	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	1	74	theme	fraction	135:142	arg1	components					85:94	The main components	76:94	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour	76:157	The main components of the non-starch polysaccharide (NSP) fraction of wheat flour are arabinoxylan (AX) and β-glucan.
31865461	7	75	theme	SCFAs	1186:1190	arg1	concentration					1163:1175	concentration	1163:1175	concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups	1163:1305	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	0	76	theme	polysaccharides	59:73	arg1	mixtures					34:41	mixtures	34:41	mixtures of cereal grain polysaccharides	34:73	Comparative prebiotic activity of mixtures of cereal grain polysaccharides.
31865461	7	77	theme	major	1430:1434	arg1	source					1436:1441	major source	1430:1441	major source of cereal fibre in the diet	1430:1469	The greatest prebiotic activity, based on concentration of total SCFAs and increases in total bacteria as well as beneficial Bifidobacterium and Clostridium coccoides/Eubacterium groups, was observed when AX and β-glucan were combined at a 3:1 ratio, which corresponds to their ratios in wheat flour which is major source of cereal fibre in the diet.
31865461	4	78	dep	in	585:586	arg1	vitro					588:592	vitro	588:592	vitro	588:592	AX and β-glucan were therefore tested in in vitro fermentation studies to assess their prebiotic activity when used individually and/or in different ratios.
31865461	5	79	theme	flow	840:843	arg1	cytometry					845:853	flow cytometry	840:853	flow cytometry with fluorescence in situ hybridisation (Flow-FISH)	840:905	Short-chain fatty-acids (SCFAs) produced from in vitro fermentation were measured using HPLC and bacterial populations were measured using flow cytometry with fluorescence in situ hybridisation (Flow-FISH).
31865461	3	80	from	present	464:470	arg1	foods					485:489	the major foods	475:489	the major foods consumed	475:498	Therefore, it was hypothesised that these NSPs could act synergistically when fermented in vitro at the ratios present in the major foods consumed, resulting in increased prebiotic activity.
31865461	6	81	theme	bifidogenic	959:969	arg1	activity					971:978	a significant bifidogenic activity	945:978	a significant bifidogenic activity	945:978	Fermentation of AX alone resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate, after 8-24 h of fermentation, however β-glucan alone did not show prebiotic activity.
29693369	4	0	theme	large	991:995	arg1	amounts					997:1003	large amounts	991:1003	large amounts of nonaggregated bacteria	991:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	0	theme	large	991:995	arg1	bacteria					1022:1029	nonaggregated bacteria	1008:1029	nonaggregated bacteria	1008:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	5	1	theme	shell	1129:1133	arg1	properties					1111:1120	the mechanical properties	1096:1120	the mechanical properties of the shell	1096:1133	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	4	2	theme	bacteria	872:879	arg1	aggregation					853:863	aggregation	853:863	aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	853:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	3	theme	different	903:911	arg1	process					962:968	a new scalable process	947:968	a new scalable process that easily leads to large amounts of nonaggregated bacteria	947:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	3	theme	different	903:911	arg1	procedures-among					921:936	different coating procedures-among	903:936	different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	903:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	1	4	theme	possible	179:186	arg1	epidermidis					133:143	Staphylococcus epidermidis	118:143	Staphylococcus epidermidis	118:143	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	1	4	theme	possible	179:186	arg1	bacteria					101:108	Commensal skin bacteria	86:108	Commensal skin bacteria such as Staphylococcus epidermidis	86:143	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	1	4	theme	possible	179:186	arg1	components					188:197	possible components	179:197	possible components in skin-care and skin-health products	179:235	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	3	5	theme	layer-by-layer	552:565	arg1	assembly					567:574	layer-by-layer assembly	552:574	layer-by-layer assembly	552:574	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	5	6	theme	outmost	1255:1261	arg1	layer					1263:1267	its outmost layer	1251:1267	its outmost layer	1251:1267	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	4	7	theme	scalable	953:960	arg1	process					962:968	a new scalable process	947:968	a new scalable process that easily leads to large amounts of nonaggregated bacteria	947:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	7	theme	scalable	953:960	arg1	procedures-among					921:936	different coating procedures-among	903:936	different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	903:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	1	8	from	components	188:197	arg1	products					228:235	skin-care and skin-health products	202:235	skin-care and skin-health products	202:235	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	5	9	theme	layer	1263:1267	arg1	thickness					1227:1235	shell thickness	1221:1235	shell thickness	1221:1235	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	5	9	theme	layer	1263:1267	arg1	charge					1241:1246	charge	1241:1246	charge	1241:1246	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	4	10	theme	shell	773:777	arg1	degree					843:848	the degree	839:848	the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	839:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	10	theme	shell	773:777	arg1	composition					754:764	the composition	750:764	the composition of the shell	750:777	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	10	theme	shell	773:777	arg1	thickness					784:792	its thickness	780:792	its thickness	780:792	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	10	theme	shell	773:777	arg1	charge					799:804	the charge	795:804	the charge of the last deposited layer	795:832	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	2	11	dep	free	326:329	arg1	proliferate					334:344	proliferate	334:344	to proliferate	331:344	However, considering the potentially adverse effects of commensal skin bacteria if left free to proliferate, it is crucial to develop methodologies that are capable of maintaining bacteria viability while controlling their proliferation.
29693369	5	12	theme	sites	1315:1319	arg1	diffusion					1287:1295	the diffusion	1283:1295	the diffusion of unpaired amine sites	1283:1319	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	4	13	theme	growth	730:735	arg1	viability					688:696	the viability	684:696	the viability of the cells	684:709	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	13	theme	growth	730:735	arg1	delay					721:725	their delay	715:725	their delay of growth	715:735	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	5	14	theme	mechanical	1100:1109	arg1	properties					1111:1120	the mechanical properties	1096:1120	the mechanical properties of the shell	1096:1133	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	1	15	theme	Commensal	86:94	arg1	epidermidis					133:143	Staphylococcus epidermidis	118:143	Staphylococcus epidermidis	118:143	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	1	15	theme	Commensal	86:94	arg1	bacteria					101:108	Commensal skin bacteria	86:108	Commensal skin bacteria such as Staphylococcus epidermidis	86:143	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	1	15	theme	Commensal	86:94	arg1	components					188:197	possible components	179:197	possible components in skin-care and skin-health products	179:235	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	4	16	theme	cells	705:709	arg1	viability					688:696	the viability	684:696	the viability of the cells	684:709	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	16	theme	cells	705:709	arg1	delay					721:725	their delay	715:725	their delay of growth	715:735	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	1	17	theme	skin	96:99	arg1	epidermidis					133:143	Staphylococcus epidermidis	118:143	Staphylococcus epidermidis	118:143	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	1	17	theme	skin	96:99	arg1	bacteria					101:108	Commensal skin bacteria	86:108	Commensal skin bacteria such as Staphylococcus epidermidis	86:143	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	1	17	theme	skin	96:99	arg1	components					188:197	possible components	179:197	possible components in skin-care and skin-health products	179:235	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	2	18	theme	bacteria	418:425	arg1	viability					427:435	bacteria viability	418:435	bacteria viability	418:435	However, considering the potentially adverse effects of commensal skin bacteria if left free to proliferate, it is crucial to develop methodologies that are capable of maintaining bacteria viability while controlling their proliferation.
29693369	3	19	theme	polyelectrolytes	609:624	arg1	pair					591:594	a pair	589:594	a pair of synthetic polyelectrolytes	589:624	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	3	19	theme	polyelectrolytes	609:624	arg1	pair					631:634	a pair	629:634	a pair of oppositely charged polysaccharides	629:672	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	4	20	theme	aggregation	853:863	arg1	degree					843:848	the degree	839:848	the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	839:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	20	theme	aggregation	853:863	arg1	composition					754:764	the composition	750:764	the composition of the shell	750:777	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	20	theme	aggregation	853:863	arg1	thickness					784:792	its thickness	780:792	its thickness	780:792	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	20	theme	aggregation	853:863	arg1	charge					799:804	the charge	795:804	the charge of the last deposited layer	795:832	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	1	21	theme	skin-health	216:226	arg1	products					228:235	skin-care and skin-health products	202:235	skin-care and skin-health products	202:235	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	6	22	theme	topical	1414:1420	arg1	applications					1422:1433	daily topical applications	1408:1433	daily topical applications	1408:1433	The lag times of growth are sufficient to prevent proliferation for daily topical applications.
29693369	4	23	theme	deposited	818:826	arg1	layer					828:832	the last deposited layer	809:832	the last deposited layer	809:832	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	3	24	theme	epidermidis	500:510	arg1	shells					515:520	S. epidermidis in shells	497:520	S. epidermidis in shells of increasing thickness using layer-by-layer assembly	497:574	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	6	25	theme	daily	1408:1412	arg1	applications					1422:1433	daily topical applications	1408:1433	daily topical applications	1408:1433	The lag times of growth are sufficient to prevent proliferation for daily topical applications.
29693369	5	26	theme	complex	1191:1197	arg1	effect					1161:1166	the bacteriostatic effect	1142:1166	the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer	1142:1267	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	3	27	theme	synthetic	599:607	arg1	polyelectrolytes					609:624	synthetic polyelectrolytes	599:624	synthetic polyelectrolytes	599:624	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	5	28	theme	unpaired	1300:1307	arg1	sites					1315:1319	unpaired amine sites	1300:1319	unpaired amine sites	1300:1319	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	3	29	theme	in	512:513	arg1	shells					515:520	S. epidermidis in shells	497:520	S. epidermidis in shells of increasing thickness using layer-by-layer assembly	497:574	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	0	30	theme	epidermidis	41:51	arg1	Growth					16:21	the Growth	12:21	the Growth of Staphylococcus epidermidis	12:51	Controlling the Growth of Staphylococcus epidermidis by Layer-By-Layer Encapsulation.
29693369	2	31	theme	adverse	275:281	arg1	effects					283:289	the potentially adverse effects	259:289	the potentially adverse effects of commensal skin bacteria	259:316	However, considering the potentially adverse effects of commensal skin bacteria if left free to proliferate, it is crucial to develop methodologies that are capable of maintaining bacteria viability while controlling their proliferation.
29693369	5	32	theme	amine	1309:1313	arg1	sites					1315:1319	unpaired amine sites	1300:1319	unpaired amine sites	1300:1319	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	4	33	theme	layer	828:832	arg1	degree					843:848	the degree	839:848	the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	839:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	33	theme	layer	828:832	arg1	composition					754:764	the composition	750:764	the composition of the shell	750:777	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	33	theme	layer	828:832	arg1	thickness					784:792	its thickness	780:792	its thickness	780:792	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	33	theme	layer	828:832	arg1	charge					799:804	the charge	795:804	the charge of the last deposited layer	795:832	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	3	34	theme	S.	497:498	arg1	shells					515:520	S. epidermidis in shells	497:520	S. epidermidis in shells of increasing thickness using layer-by-layer assembly	497:574	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	0	35	theme	Layer-By-Layer	56:69	arg1	Encapsulation					71:83	Layer-By-Layer Encapsulation	56:83	Layer-By-Layer Encapsulation	56:83	Controlling the Growth of Staphylococcus epidermidis by Layer-By-Layer Encapsulation.
29693369	5	36	theme	bacteriostatic	1146:1159	arg1	effect					1161:1166	the bacteriostatic effect	1142:1166	the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer	1142:1267	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	5	37	theme	polyelectrolyte	1175:1189	arg1	complex					1191:1197	the polyelectrolyte complex	1171:1197	the polyelectrolyte complex	1171:1197	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	3	38	theme	increasing	525:534	arg1	thickness					536:544	increasing thickness	525:544	increasing thickness using layer-by-layer assembly	525:574	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	4	39	theme	nonaggregated	1008:1020	arg1	bacteria					1022:1029	nonaggregated bacteria	1008:1029	nonaggregated bacteria	1008:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	6	40	theme	growth	1357:1362	arg1	times					1348:1352	The lag times	1340:1352	The lag times of growth	1340:1362	The lag times of growth are sufficient to prevent proliferation for daily topical applications.
29693369	6	40	theme	growth	1357:1362	arg1	sufficient					1368:1377	sufficient	1368:1377	sufficient	1368:1377	The lag times of growth are sufficient to prevent proliferation for daily topical applications.
29693369	3	41	theme	thickness	536:544	arg1	shells					515:520	S. epidermidis in shells	497:520	S. epidermidis in shells of increasing thickness using layer-by-layer assembly	497:574	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	4	42	theme	last	813:816	arg1	layer					828:832	the last deposited layer	809:832	the last deposited layer	809:832	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	43	theme	coating	913:919	arg1	process					962:968	a new scalable process	947:968	a new scalable process that easily leads to large amounts of nonaggregated bacteria	947:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	43	theme	coating	913:919	arg1	procedures-among					921:936	different coating procedures-among	903:936	different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	903:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	2	44	theme	skin	304:307	arg1	bacteria					309:316	commensal skin bacteria	294:316	commensal skin bacteria	294:316	However, considering the potentially adverse effects of commensal skin bacteria if left free to proliferate, it is crucial to develop methodologies that are capable of maintaining bacteria viability while controlling their proliferation.
29693369	5	45	theme	shell	1221:1225	arg1	thickness					1227:1235	shell thickness	1221:1235	shell thickness	1221:1235	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	2	46	theme	bacteria	309:316	arg1	effects					283:289	the potentially adverse effects	259:289	the potentially adverse effects of commensal skin bacteria	259:316	However, considering the potentially adverse effects of commensal skin bacteria if left free to proliferate, it is crucial to develop methodologies that are capable of maintaining bacteria viability while controlling their proliferation.
29693369	2	47	theme	commensal	294:302	arg1	bacteria					309:316	commensal skin bacteria	294:316	commensal skin bacteria	294:316	However, considering the potentially adverse effects of commensal skin bacteria if left free to proliferate, it is crucial to develop methodologies that are capable of maintaining bacteria viability while controlling their proliferation.
29693369	6	48	theme	lag	1344:1346	arg1	times					1348:1352	The lag times	1340:1352	The lag times of growth	1340:1362	The lag times of growth are sufficient to prevent proliferation for daily topical applications.
29693369	6	48	theme	lag	1344:1346	arg1	sufficient					1368:1377	sufficient	1368:1377	sufficient	1368:1377	The lag times of growth are sufficient to prevent proliferation for daily topical applications.
29693369	5	49	theme	bacteria	1066:1073	arg1	growth					1056:1061	the growth	1052:1061	the growth of bacteria	1052:1073	We demonstrate that the growth of bacteria is not controlled by the mechanical properties of the shell but by the bacteriostatic effect of the polyelectrolyte complex, which depends on the shell thickness and charge of its outmost layer, and involves the diffusion of unpaired amine sites through the shell.
29693369	3	50	theme	charged	650:656	arg1	polysaccharides					658:672	oppositely charged polysaccharides	639:672	oppositely charged polysaccharides	639:672	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	1	51	theme	skin-care	202:210	arg1	products					228:235	skin-care and skin-health products	202:235	skin-care and skin-health products	202:235	Commensal skin bacteria such as Staphylococcus epidermidis are currently being considered as possible components in skin-care and skin-health products.
29693369	4	52	theme	bacteria	1022:1029	arg1	amounts					997:1003	large amounts	991:1003	large amounts of nonaggregated bacteria	991:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	52	theme	bacteria	1022:1029	arg1	bacteria					1022:1029	nonaggregated bacteria	1008:1029	nonaggregated bacteria	1008:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	3	53	theme	polysaccharides	658:672	arg1	pair					591:594	a pair	589:594	a pair of synthetic polyelectrolytes	589:624	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	3	53	theme	polysaccharides	658:672	arg1	pair					631:634	a pair	629:634	a pair of oppositely charged polysaccharides	629:672	Here, we encapsulate S. epidermidis in shells of increasing thickness using layer-by-layer assembly, with either a pair of synthetic polyelectrolytes or a pair of oppositely charged polysaccharides.
29693369	4	54	theme	new	949:951	arg1	process					962:968	a new scalable process	947:968	a new scalable process that easily leads to large amounts of nonaggregated bacteria	947:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29693369	4	54	theme	new	949:951	arg1	procedures-among					921:936	different coating procedures-among	903:936	different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria	903:1029	We study the viability of the cells and their delay of growth depending on the composition of the shell, its thickness, the charge of the last deposited layer, and the degree of aggregation of the bacteria which is varied using different coating procedures-among which is a new scalable process that easily leads to large amounts of nonaggregated bacteria.
29515611	10	0	from	micro-domains	1774:1786	arg1	wall					1800:1803	the cell wall	1791:1803	the cell wall of a given cell	1791:1819	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	10	1	theme	degradation	1740:1750	arg1	pattern					1752:1758	the degradation pattern	1736:1758	the degradation pattern	1736:1758	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	3	2	theme	synchrotron	619:629	arg1	facilities					631:640	synchrotron facilities	619:640	synchrotron facilities	619:640	In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls.
29515611	10	3	theme	given	1810:1814	arg1	cell					1816:1819	a given cell	1808:1819	a given cell	1808:1819	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	11	4	theme	Fluorescence	1822:1833	arg1	quantification					1845:1858	Fluorescence intensity quantification	1822:1858	Fluorescence intensity quantification	1822:1858	Fluorescence intensity quantification showed that the enzymes were not evenly distributed, and their amount increased progressively on degradable cell walls.
29515611	7	5	theme	cell	1294:1297	arg1	walls					1299:1303	cell walls	1294:1303	cell walls during degradation	1294:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	1	6	theme	Tracking	214:221	arg1	localization					230:241	Tracking enzyme localization and following the local biochemical modification of the substrate	214:307	localization	230:241	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	7	7	theme	Microfluidic	1182:1193	arg1	microspectroscopy					1201:1217	Microfluidic FT-IR microspectroscopy	1182:1217	Microfluidic FT-IR microspectroscopy	1182:1217	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	3	8	used	used	652:655	arg2	facilities					631:640	synchrotron facilities	619:640	synchrotron facilities	619:640	In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls.
29515611	0	9	theme	Cell	159:162	arg1	Walls					164:168	Cell Walls	159:168	Cell Walls	159:168	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	3	10	theme	enzymatic	670:678	arg1	degradation					680:690	the enzymatic degradation	666:690	the enzymatic degradation of lignocellulosic biomass	666:717	In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls.
29515611	1	11	theme	local	261:265	arg1	modification					279:290	the local biochemical modification	257:290	the local biochemical modification	257:290	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	3	12	theme	lignocellulosic	695:709	arg1	biomass					711:717	lignocellulosic biomass	695:717	lignocellulosic biomass	695:717	In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls.
29515611	0	13	theme	Infrared	186:193	arg1	Microspectroscopy					195:211	Microfluidic Infrared Microspectroscopy	173:211	Microfluidic Infrared Microspectroscopy	173:211	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	3	14	theme	biomass	711:717	arg1	degradation					680:690	the enzymatic degradation	666:690	the enzymatic degradation of lignocellulosic biomass	666:717	In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls.
29515611	4	15	from	absence	897:903	arg1	walls					924:928	cell walls	919:928	cell walls	919:928	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	4	16	theme	Multichannel	766:777	arg1	imaging					796:802	Multichannel autofluorescence imaging	766:802	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm	766:867	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	0	17	theme	Tracking	70:77	arg1	Localization					86:97	Tracking Enzyme Localization	70:97	Tracking Enzyme Localization by Protein Autofluorescence	70:125	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	1	18	theme	enzymatic	386:394	arg1	degradation					396:406	enzymatic degradation	386:406	enzymatic degradation	386:406	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	4	19	from	presence	885:892	arg1	walls					924:928	cell walls	919:928	cell walls	919:928	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	11	20	theme	degradable	1957:1966	arg1	walls					1973:1977	degradable cell walls	1957:1977	degradable cell walls	1957:1977	Fluorescence intensity quantification showed that the enzymes were not evenly distributed, and their amount increased progressively on degradable cell walls.
29515611	0	21	theme	Protein	102:108	arg1	Autofluorescence					110:125	Protein Autofluorescence	102:125	Protein Autofluorescence	102:125	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	7	22	from	polysaccharides	1275:1289	arg1	walls					1299:1303	cell walls	1294:1303	cell walls during degradation	1294:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	7	22	from	polysaccharides	1275:1289	arg1	tracking					1242:1249	time-lapse tracking	1231:1249	time-lapse tracking of local changes in the polysaccharides in cell walls during degradation	1231:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	0	23	theme	Biomass	50:56	arg1	Hydrolysis					58:67	Lignocellulosic Biomass Hydrolysis	34:67	Lignocellulosic Biomass Hydrolysis	34:67	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	6	24	theme	cell	1170:1173	arg1	walls					1175:1179	their surrounding cell walls	1152:1179	their surrounding cell walls	1152:1179	Consistent variations in the enzyme concentration were found locally for cell cavities and their surrounding cell walls.
29515611	10	25	theme	multiscale	1608:1617	arg1	imaging					1619:1625	Fluorescence multiscale imaging	1595:1625	Fluorescence multiscale imaging	1595:1625	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	4	26	theme	compounds	832:840	arg1	imaging					796:802	Multichannel autofluorescence imaging	766:802	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm	766:867	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	2	27	theme	enzyme	463:468	arg1	labeling					470:477	enzyme labeling	463:477	enzyme labeling	463:477	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	0	28	theme	Synchrotron	0:10	arg1	Imaging					23:29	Synchrotron Time-Lapse Imaging	0:29	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.	0:212	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	4	29	dep	protein	811:817	arg1	the					807:809	the	807:809	the	807:809	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	2	30	theme	biopolymers	526:536	arg1	modifications					509:521	the biochemical modifications	493:521	the biochemical modifications of biopolymers found in plant cell walls	493:562	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	5	31	theme	fluorescence	1026:1037	arg1	variations					1049:1058	the fluorescence intensity variations	1022:1058	the fluorescence intensity variations	1022:1058	Image analysis was used to quantify the fluorescence intensity variations.
29515611	4	32	theme	enzymes	908:914	arg1	absence					897:903	absence	897:903	absence	897:903	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	4	32	theme	enzymes	908:914	arg1	presence					885:892	presence	885:892	presence	885:892	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	0	33	theme	Lignocellulosic	34:48	arg1	Hydrolysis					58:67	Lignocellulosic Biomass Hydrolysis	34:67	Lignocellulosic Biomass Hydrolysis	34:67	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	1	34	theme	plant	366:370	arg1	walls					377:381	lignocellulosic plant cell walls	350:381	lignocellulosic plant cell walls	350:381	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	12	35	theme	adjacent	2000:2007	arg1	cells					2009:2013	adjacent cells	2000:2013	adjacent cells	2000:2013	During degradation, adjacent cells were separated and the cell wall fragmented until complete degradation.
29515611	2	36	theme	cell	553:556	arg1	walls					558:562	plant cell walls	547:562	plant cell walls	547:562	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	4	37	theme	cell	919:922	arg1	walls					924:928	cell walls	919:928	cell walls	919:928	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	2	38	theme	Time-lapse	409:418	arg1	studies					420:426	Time-lapse studies	409:426	Time-lapse studies using conventional imaging	409:453	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	0	39	theme	Hydrolysis	58:67	arg1	Imaging					23:29	Synchrotron Time-Lapse Imaging	0:29	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.	0:212	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	1	40	theme	walls	377:381	arg1	recalcitrance					333:345	the recalcitrance	329:345	the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation	329:406	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	7	41	from	tracking	1242:1249	arg1	polysaccharides					1275:1289	the polysaccharides	1271:1289	the polysaccharides in cell walls during degradation	1271:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	2	42	dep	following	483:491	arg1	achieved					588:595	achieved	588:595	cannot be easily achieved	571:595	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	1	43	theme	biochemical	267:277	arg1	modification					279:290	the local biochemical modification	257:290	the local biochemical modification	257:290	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	0	44	dep	Imaging	23:29	arg1	Localization					86:97	Tracking Enzyme Localization	70:97	Tracking Enzyme Localization by Protein Autofluorescence	70:125	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	0	44	dep	Imaging	23:29	arg1	Modification					143:154	Biochemical Modification	131:154	Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy	131:211	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	9	45	theme	lignified	1535:1543	arg1	walls					1550:1554	lignified cell walls	1535:1554	lignified cell walls	1535:1554	Combining the fluorescence and FT-IR information yielded the conclusion that enzymes did not bind to lignified cell walls, which were consequently not degraded.
29515611	10	46	theme	initial	1700:1706	arg1	composition					1720:1730	the initial biochemical composition	1696:1730	the initial biochemical composition	1696:1730	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	7	47	theme	time-lapse	1231:1240	arg1	tracking					1242:1249	time-lapse tracking	1231:1249	time-lapse tracking of local changes in the polysaccharides in cell walls during degradation	1231:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	1	48	theme	substrate	299:307	arg1	localization					230:241	Tracking enzyme localization and following the local biochemical modification of the substrate	214:307	localization	230:241	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	7	49	theme	FT-IR	1195:1199	arg1	microspectroscopy					1201:1217	Microfluidic FT-IR microspectroscopy	1182:1217	Microfluidic FT-IR microspectroscopy	1182:1217	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	3	50	theme	present	605:611	arg1	work					613:616	the present work	601:616	the present work	601:616	In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls.
29515611	1	51	theme	enzyme	223:228	arg1	localization					230:241	Tracking enzyme localization and following the local biochemical modification of the substrate	214:307	localization	230:241	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	7	52	theme	local	1254:1258	arg1	changes					1260:1266	local changes	1254:1266	local changes in the polysaccharides in cell walls during degradation	1254:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	10	53	from	variability	1676:1686	arg1	composition					1720:1730	the initial biochemical composition	1696:1730	the initial biochemical composition	1696:1730	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	10	53	from	variability	1676:1686	arg1	pattern					1752:1758	the degradation pattern	1736:1758	the degradation pattern	1736:1758	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	2	54	located	found	538:542	arg1	walls					558:562	plant cell walls	547:562	plant cell walls	547:562	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	2	54	located	found	538:542	arg2	biopolymers					526:536	biopolymers	526:536	biopolymers found in plant cell walls	526:562	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	11	55	theme	intensity	1835:1843	arg1	quantification					1845:1858	Fluorescence intensity quantification	1822:1858	Fluorescence intensity quantification	1822:1858	Fluorescence intensity quantification showed that the enzymes were not evenly distributed, and their amount increased progressively on degradable cell walls.
29515611	4	56	dep	presence	885:892	arg1	the					881:883	the	881:883	the	881:883	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	6	57	theme	Consistent	1061:1070	arg1	variations					1072:1081	Consistent variations	1061:1081	Consistent variations in the enzyme concentration	1061:1109	Consistent variations in the enzyme concentration were found locally for cell cavities and their surrounding cell walls.
29515611	8	58	theme	cellulose	1379:1387	arg1	degradation					1389:1399	cellulose degradation	1379:1399	cellulose degradation using a Celluclast® preparation	1379:1431	Hemicellulose degradation was found to occur prior to cellulose degradation using a Celluclast® preparation.
29515611	0	59	theme	Walls	164:168	arg1	Localization					86:97	Tracking Enzyme Localization	70:97	Tracking Enzyme Localization by Protein Autofluorescence	70:125	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	0	59	theme	Walls	164:168	arg1	Modification					143:154	Biochemical Modification	131:154	Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy	131:211	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	8	60	theme	Hemicellulose	1325:1337	arg1	degradation					1339:1349	Hemicellulose degradation	1325:1349	Hemicellulose degradation	1325:1349	Hemicellulose degradation was found to occur prior to cellulose degradation using a Celluclast® preparation.
29515611	11	61	theme	cell	1968:1971	arg1	walls					1973:1977	degradable cell walls	1957:1977	degradable cell walls	1957:1977	Fluorescence intensity quantification showed that the enzymes were not evenly distributed, and their amount increased progressively on degradable cell walls.
29515611	10	62	theme	cell	1795:1798	arg1	wall					1800:1803	the cell wall	1791:1803	the cell wall of a given cell	1791:1819	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	0	63	theme	Microfluidic	173:184	arg1	Microspectroscopy					195:211	Microfluidic Infrared Microspectroscopy	173:211	Microfluidic Infrared Microspectroscopy	173:211	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	5	64	theme	Image	986:990	arg1	analysis					992:999	Image analysis	986:999	Image analysis	986:999	Image analysis was used to quantify the fluorescence intensity variations.
29515611	8	65	theme	Celluclast®	1409:1419	arg1	preparation					1421:1431	a Celluclast® preparation	1407:1431	a Celluclast® preparation	1407:1431	Hemicellulose degradation was found to occur prior to cellulose degradation using a Celluclast® preparation.
29515611	10	66	dep	composition	1720:1730	arg1	both					1688:1691	both	1688:1691	both	1688:1691	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	5	67	used	used	1005:1008	arg2	analysis					992:999	Image analysis	986:999	Image analysis	986:999	Image analysis was used to quantify the fluorescence intensity variations.
29515611	4	68	theme	protein	811:817	arg1	imaging					796:802	Multichannel autofluorescence imaging	766:802	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm	766:867	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	0	69	theme	Enzyme	79:84	arg1	Localization					86:97	Tracking Enzyme Localization	70:97	Tracking Enzyme Localization by Protein Autofluorescence	70:125	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	6	70	theme	enzyme	1090:1095	arg1	concentration					1097:1109	the enzyme concentration	1086:1109	the enzyme concentration	1086:1109	Consistent variations in the enzyme concentration were found locally for cell cavities and their surrounding cell walls.
29515611	7	71	from	changes	1260:1266	arg1	polysaccharides					1275:1289	the polysaccharides	1271:1289	the polysaccharides in cell walls during degradation	1271:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	4	72	theme	autofluorescence	779:794	arg1	imaging					796:802	Multichannel autofluorescence imaging	766:802	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm	766:867	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	4	73	attach	presence	885:892	arg2	enzymes					908:914	enzymes	908:914	enzymes	908:914	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	4	73	attach	presence	885:892	arg1	walls					924:928	cell walls	919:928	cell walls	919:928	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	4	74	from	nm	866:867	arg1	imaging					796:802	Multichannel autofluorescence imaging	766:802	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm	766:867	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	5	75	theme	intensity	1039:1047	arg1	variations					1049:1058	the fluorescence intensity variations	1022:1058	the fluorescence intensity variations	1022:1058	Image analysis was used to quantify the fluorescence intensity variations.
29515611	0	76	theme	Biochemical	131:141	arg1	Modification					143:154	Biochemical Modification	131:154	Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy	131:211	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	9	77	theme	fluorescence	1448:1459	arg1	information					1471:1481	the fluorescence and FT-IR information	1444:1481	information	1471:1481	Combining the fluorescence and FT-IR information yielded the conclusion that enzymes did not bind to lignified cell walls, which were consequently not degraded.
29515611	6	78	from	variations	1072:1081	arg1	concentration					1097:1109	the enzyme concentration	1086:1109	the enzyme concentration	1086:1109	Consistent variations in the enzyme concentration were found locally for cell cavities and their surrounding cell walls.
29515611	10	79	theme	cell	1816:1819	arg1	wall					1800:1803	the cell wall	1791:1803	the cell wall of a given cell	1791:1819	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	0	80	theme	Time-Lapse	12:21	arg1	Imaging					23:29	Synchrotron Time-Lapse Imaging	0:29	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.	0:212	Synchrotron Time-Lapse Imaging of Lignocellulosic Biomass Hydrolysis: Tracking Enzyme Localization by Protein Autofluorescence and Biochemical Modification of Cell Walls by Microfluidic Infrared Microspectroscopy.
29515611	9	81	theme	FT-IR	1465:1469	arg1	information					1471:1481	the fluorescence and FT-IR information	1444:1481	information	1471:1481	Combining the fluorescence and FT-IR information yielded the conclusion that enzymes did not bind to lignified cell walls, which were consequently not degraded.
29515611	6	82	theme	surrounding	1158:1168	arg1	walls					1175:1179	their surrounding cell walls	1152:1179	their surrounding cell walls	1152:1179	Consistent variations in the enzyme concentration were found locally for cell cavities and their surrounding cell walls.
29515611	10	83	theme	Fluorescence	1595:1606	arg1	imaging					1619:1625	Fluorescence multiscale imaging	1595:1625	Fluorescence multiscale imaging	1595:1625	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	4	84	theme	phenolic	823:830	arg1	compounds					832:840	phenolic compounds	823:840	phenolic compounds	823:840	Multichannel autofluorescence imaging of the protein and phenolic compounds after excitation at 275 nm highlighted the presence or absence of enzymes on cell walls and made it possible to track them during the reaction.
29515611	12	85	theme	fragmented	2048:2057	arg1	wall					2043:2046	the cell wall fragmented	2034:2057	the cell wall fragmented	2034:2057	During degradation, adjacent cells were separated and the cell wall fragmented until complete degradation.
29515611	2	86	theme	biochemical	497:507	arg1	modifications					509:521	the biochemical modifications	493:521	the biochemical modifications of biopolymers found in plant cell walls	493:562	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	7	87	theme	changes	1260:1266	arg1	tracking					1242:1249	time-lapse tracking	1231:1249	time-lapse tracking of local changes in the polysaccharides in cell walls during degradation	1231:1322	Microfluidic FT-IR microspectroscopy allowed for time-lapse tracking of local changes in the polysaccharides in cell walls during degradation.
29515611	1	88	theme	lignocellulosic	350:364	arg1	walls					377:381	lignocellulosic plant cell walls	350:381	lignocellulosic plant cell walls	350:381	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	12	89	theme	complete	2065:2072	arg1	degradation					2074:2084	complete degradation	2065:2084	complete degradation	2065:2084	During degradation, adjacent cells were separated and the cell wall fragmented until complete degradation.
29515611	6	90	theme	cell	1134:1137	arg1	cavities					1139:1146	cell cavities	1134:1146	cell cavities	1134:1146	Consistent variations in the enzyme concentration were found locally for cell cavities and their surrounding cell walls.
29515611	10	91	theme	FT-IR	1631:1635	arg1	microspectroscopy					1637:1653	FT-IR microspectroscopy	1631:1653	FT-IR microspectroscopy	1631:1653	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	1	92	dep	localization	230:241	arg1	modification					279:290	the local biochemical modification	257:290	the local biochemical modification	257:290	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	1	93	theme	cell	372:375	arg1	walls					377:381	lignocellulosic plant cell walls	350:381	lignocellulosic plant cell walls	350:381	Tracking enzyme localization and following the local biochemical modification of the substrate should help explain the recalcitrance of lignocellulosic plant cell walls to enzymatic degradation.
29515611	2	94	theme	plant	547:551	arg1	walls					558:562	plant cell walls	547:562	plant cell walls	547:562	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	3	95	theme	cell	754:757	arg1	walls					759:763	the cell walls	750:763	the cell walls	750:763	In the present work, synchrotron facilities have been used to image the enzymatic degradation of lignocellulosic biomass without labeling the enzyme or the cell walls.
29515611	12	96	theme	cell	2038:2041	arg1	wall					2043:2046	the cell wall fragmented	2034:2057	the cell wall fragmented	2034:2057	During degradation, adjacent cells were separated and the cell wall fragmented until complete degradation.
29515611	10	97	theme	unexpected	1665:1674	arg1	variability					1676:1686	an unexpected variability	1662:1686	an unexpected variability both in the initial biochemical composition and the degradation pattern	1662:1758	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	10	98	theme	biochemical	1708:1718	arg1	composition					1720:1730	the initial biochemical composition	1696:1730	the initial biochemical composition	1696:1730	Fluorescence multiscale imaging and FT-IR microspectroscopy showed an unexpected variability both in the initial biochemical composition and the degradation pattern, highlighting micro-domains in the cell wall of a given cell.
29515611	2	99	theme	conventional	434:445	arg1	imaging					447:453	conventional imaging	434:453	conventional imaging	434:453	Time-lapse studies using conventional imaging require enzyme labeling and following the biochemical modifications of biopolymers found in plant cell walls, which cannot be easily achieved.
29515611	9	100	theme	cell	1545:1548	arg1	walls					1550:1554	lignified cell walls	1535:1554	lignified cell walls	1535:1554	Combining the fluorescence and FT-IR information yielded the conclusion that enzymes did not bind to lignified cell walls, which were consequently not degraded.
29495256	6	0	theme	well-established	1095:1110	arg1	Fibrobactersuccinogenes					1168:1190	Fibrobactersuccinogenes	1168:1190	Fibrobactersuccinogenes	1168:1190	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	0	theme	well-established	1095:1110	arg1	Ruminococcusflavefaciens					1139:1162	Ruminococcusflavefaciens	1139:1162	Ruminococcusflavefaciens	1139:1162	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	0	theme	well-established	1095:1110	arg1	utilizers					1128:1136	well-established rumen cellulose utilizers	1095:1136	well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes)	1095:1191	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	8	1	theme	metabolic	1621:1629	arg1	trait					1631:1635	a ruminal metabolic trait	1611:1635	a ruminal metabolic trait shared across vast phylogenetic distances	1611:1677	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	1	theme	metabolic	1621:1629	arg1	utilization					1596:1606	cellulose utilization	1586:1606	cellulose utilization	1586:1606	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	3	2	theme	bacterial	689:697	arg1	sequences					713:721	bacterial 16S rRNA gene sequences	689:721	bacterial 16S rRNA gene sequences in their respective samples	689:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	1	3	theme	activities	256:265	arg1	ability					176:182	The ability	172:182	The ability of ruminants to utilize cellulosic biomass	172:225	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	1	3	theme	activities	256:265	arg1	result					232:237	a result	230:237	a result of the metabolic activities of symbiotic microbial communities that reside in the rumen	230:325	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	5	4	contain	have	996:999	arg1	set					889:891	each set	884:891	each set of replicate cellulose supplemented cultures originating from a sampled rumen environment	884:981	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	5	4	contain	have	996:999	arg1	cellulose					906:914	replicate cellulose	896:914	replicate cellulose supplemented cultures originating from a sampled rumen environment	896:981	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	5	4	contain	have	996:999	arg2	composition					1022:1032	a distinct bacterial composition	1001:1032	a distinct bacterial composition	1001:1032	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	2	5	used	used	438:441	arg2	approach					425:432	a selection-based batch culturing approach	391:432	a selection-based batch culturing approach	391:432	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	3	6	theme	beef	575:578	arg1	cows					580:583	three beef cows	569:583	three beef cows maintained on a forage diet	569:611	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	1	7	theme	symbiotic	270:278	arg1	communities					290:300	symbiotic microbial communities	270:300	symbiotic microbial communities that reside in the rumen	270:325	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	3	8	theme	sequences	713:721	arg1	%					684:684	41.6-50.0%	675:684	41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples	675:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	8	theme	sequences	713:721	arg1	sequences					713:721	bacterial 16S rRNA gene sequences	689:721	bacterial 16S rRNA gene sequences in their respective samples	689:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	4	9	theme	rumen	858:862	arg1	samples					864:870	all rumen samples	854:870	all rumen samples	854:870	Despite this high level of overlap, only one OTU was enriched in cellulose-supplemented cultures from all rumen samples.
29495256	6	10	theme	bacterial	1279:1287	arg1	species					1289:1295	currently defined bacterial species	1261:1295	currently defined bacterial species	1261:1295	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	1	11	theme	cellulosic	208:217	arg1	biomass					219:225	cellulosic biomass	208:225	cellulosic biomass	208:225	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	7	12	theme	candidate	1382:1390	arg1	Saccharibacteria					1399:1414	the candidate phylum Saccharibacteria	1378:1414	the candidate phylum Saccharibacteria (1 OTU)	1378:1422	The latter were affiliated to Prevotella (1 OTU), Ruminococcaceae (3 OTUs), and the candidate phylum Saccharibacteria (1 OTU), respectively.
29495256	7	12	theme	candidate	1382:1390	arg1	OTU					1419:1421	1 OTU	1417:1421	1 OTU	1417:1421	The latter were affiliated to Prevotella (1 OTU), Ruminococcaceae (3 OTUs), and the candidate phylum Saccharibacteria (1 OTU), respectively.
29495256	0	13	from	Bacteroidetes	64:76	arg1	Identification					0:13	Identification	0:13	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.	0:170	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	0	13	from	Bacteroidetes	64:76	arg1	Species					39:45	Uncultured Bacterial Species	18:45	Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria	18:108	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	0	14	theme	Beef	161:164	arg1	Cows					166:169	Beef Cows	161:169	Beef Cows	161:169	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	8	15	theme	range	1755:1759	arg1	selection					1734:1742	the selection	1730:1742	the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides	1730:1838	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	6	16	theme	sequence	1240:1247	arg1	identity					1249:1256	high nucleotide sequence identity	1224:1256	high nucleotide sequence identity to currently defined bacterial species	1224:1295	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	8	17	theme	microbial	1764:1772	arg1	adaptations					1774:1784	microbial adaptations	1764:1784	microbial adaptations	1764:1784	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	6	18	theme	high	1224:1227	arg1	identity					1249:1256	high nucleotide sequence identity	1224:1256	high nucleotide sequence identity to currently defined bacterial species	1224:1295	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	3	19	theme	Taxonomic	636:644	arg1	OTUs					653:656	OTUs	653:656	OTUs	653:656	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	19	theme	Taxonomic	636:644	arg1	Units					646:650	252 Operational Taxonomic Units	620:650	252 Operational Taxonomic Units (OTUs)	620:657	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	8	20	theme	function	1513:1520	arg1	s					1522:1522	the metabolic function(s)	1499:1523	the metabolic function(s) of each enriched OTU	1499:1544	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	21	theme	plant	1807:1811	arg1	polysaccharides					1824:1838	plant structural polysaccharides	1807:1838	plant structural polysaccharides	1807:1838	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	0	22	from	Firmicutes	52:61	arg1	Identification					0:13	Identification	0:13	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.	0:170	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	0	22	from	Firmicutes	52:61	arg1	Species					39:45	Uncultured Bacterial Species	18:45	Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria	18:108	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	3	23	from	samples	743:749	arg1	%					684:684	41.6-50.0%	675:684	41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples	675:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	23	from	samples	743:749	arg1	sequences					713:721	bacterial 16S rRNA gene sequences	689:721	bacterial 16S rRNA gene sequences in their respective samples	689:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	4	24	theme	overlap	779:785	arg1	level					770:774	this high level	760:774	this high level of overlap	760:785	Despite this high level of overlap, only one OTU was enriched in cellulose-supplemented cultures from all rumen samples.
29495256	2	25	theme	selection-based	393:407	arg1	approach					425:432	a selection-based batch culturing approach	391:432	a selection-based batch culturing approach	391:432	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	0	26	theme	Cellulose	123:131	arg1	Utilizers					133:141	Candidate Cellulose Utilizers	113:141	Candidate Cellulose Utilizers from the Rumen of Beef Cows	113:169	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	8	27	theme	polysaccharides	1824:1838	arg1	digestion					1794:1802	the digestion	1790:1802	the digestion of plant structural polysaccharides	1790:1838	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	2	28	theme	candidate	455:463	arg1	consortia					495:503	candidate cellulose-utilizing bacterial consortia	455:503	candidate cellulose-utilizing bacterial consortia	455:503	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	1	29	theme	microbial	280:288	arg1	communities					290:300	symbiotic microbial communities	270:300	symbiotic microbial communities that reside in the rumen	270:325	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	6	30	theme	OTUs	1066:1069	arg1	Two					1035:1037	Two	1035:1037	Two	1035:1037	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	30	theme	OTUs	1066:1069	arg1	OTUs					1066:1069	the seven most enriched OTUs	1042:1069	the seven most enriched OTUs	1042:1069	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	8	31	theme	enriched	1533:1540	arg1	OTU					1542:1544	each enriched OTU	1528:1544	each enriched OTU	1528:1544	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	0	32	theme	Uncultured	18:27	arg1	Species					39:45	Uncultured Bacterial Species	18:45	Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria	18:108	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	5	33	theme	rumen	965:969	arg1	environment					971:981	a sampled rumen environment	955:981	a sampled rumen environment	955:981	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	2	34	theme	culturing	415:423	arg1	approach					425:432	a selection-based batch culturing approach	391:432	a selection-based batch culturing approach	391:432	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	0	35	theme	Species	39:45	arg1	Identification					0:13	Identification	0:13	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.	0:170	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	2	36	theme	bacterial	485:493	arg1	consortia					495:503	candidate cellulose-utilizing bacterial consortia	455:503	candidate cellulose-utilizing bacterial consortia	455:503	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	4	37	theme	cellulose-supplemented	817:838	arg1	cultures					840:847	cellulose-supplemented cultures	817:847	cellulose-supplemented cultures from all rumen samples	817:870	Despite this high level of overlap, only one OTU was enriched in cellulose-supplemented cultures from all rumen samples.
29495256	8	38	theme	cellulose	1586:1594	arg1	trait					1631:1635	a ruminal metabolic trait	1611:1635	a ruminal metabolic trait shared across vast phylogenetic distances	1611:1677	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	38	theme	cellulose	1586:1594	arg1	utilization					1596:1606	cellulose utilization	1586:1606	cellulose utilization	1586:1606	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	3	39	theme	rumen	541:545	arg1	contents					547:554	rumen contents	541:554	rumen contents sampled from three beef cows maintained on a forage diet	541:611	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	8	40	theme	phylogenetic	1656:1667	arg1	distances					1669:1677	vast phylogenetic distances	1651:1677	vast phylogenetic distances	1651:1677	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	5	41	theme	bacterial	1012:1020	arg1	composition					1022:1032	a distinct bacterial composition	1001:1032	a distinct bacterial composition	1001:1032	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	6	42	theme	rumen	1112:1116	arg1	Fibrobactersuccinogenes					1168:1190	Fibrobactersuccinogenes	1168:1190	Fibrobactersuccinogenes	1168:1190	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	42	theme	rumen	1112:1116	arg1	Ruminococcusflavefaciens					1139:1162	Ruminococcusflavefaciens	1139:1162	Ruminococcusflavefaciens	1139:1162	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	42	theme	rumen	1112:1116	arg1	utilizers					1128:1136	well-established rumen cellulose utilizers	1095:1136	well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes)	1095:1191	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	3	43	from	%	684:684	arg1	samples					743:749	their respective samples	726:749	their respective samples	726:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	44	theme	gene	708:711	arg1	sequences					713:721	bacterial 16S rRNA gene sequences	689:721	bacterial 16S rRNA gene sequences in their respective samples	689:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	1	45	theme	metabolic	246:254	arg1	activities					256:265	the metabolic activities	242:265	the metabolic activities of symbiotic microbial communities that reside in the rumen	242:325	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	8	46	theme	ruminal	1613:1619	arg1	trait					1631:1635	a ruminal metabolic trait	1611:1635	a ruminal metabolic trait shared across vast phylogenetic distances	1611:1677	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	46	theme	ruminal	1613:1619	arg1	utilization					1596:1606	cellulose utilization	1586:1606	cellulose utilization	1586:1606	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	3	47	theme	16S	699:701	arg1	sequences					713:721	bacterial 16S rRNA gene sequences	689:721	bacterial 16S rRNA gene sequences in their respective samples	689:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	48	theme	respective	732:741	arg1	samples					743:749	their respective samples	726:749	their respective samples	726:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	49	from	sequences	713:721	arg1	samples					743:749	their respective samples	726:749	their respective samples	726:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	50	with	culturing	515:523	arg1	cellulose					530:538	cellulose	530:538	cellulose	530:538	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	1	51	theme	ruminants	187:195	arg1	ability					176:182	The ability	172:182	The ability of ruminants to utilize cellulosic biomass	172:225	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	1	51	theme	ruminants	187:195	arg1	result					232:237	a result	230:237	a result of the metabolic activities of symbiotic microbial communities that reside in the rumen	230:325	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	8	52	theme	conducive	1717:1725	arg1	rumen					1693:1697	the rumen	1689:1697	the rumen	1689:1697	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	52	theme	conducive	1717:1725	arg1	environment					1705:1715	an environment	1702:1715	an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides	1702:1838	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	0	53	from	Saccharibacteria	93:108	arg1	Identification					0:13	Identification	0:13	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.	0:170	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	0	53	from	Saccharibacteria	93:108	arg1	Species					39:45	Uncultured Bacterial Species	18:45	Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria	18:108	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	7	54	theme	phylum	1392:1397	arg1	Saccharibacteria					1399:1414	the candidate phylum Saccharibacteria	1378:1414	the candidate phylum Saccharibacteria (1 OTU)	1378:1422	The latter were affiliated to Prevotella (1 OTU), Ruminococcaceae (3 OTUs), and the candidate phylum Saccharibacteria (1 OTU), respectively.
29495256	7	54	theme	phylum	1392:1397	arg1	OTU					1419:1421	1 OTU	1417:1421	1 OTU	1417:1421	The latter were affiliated to Prevotella (1 OTU), Ruminococcaceae (3 OTUs), and the candidate phylum Saccharibacteria (1 OTU), respectively.
29495256	0	55	theme	Cows	166:169	arg1	Rumen					152:156	the Rumen	148:156	the Rumen of Beef Cows	148:169	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	3	56	theme	forage	601:606	arg1	diet					608:611	a forage diet	599:611	a forage diet	599:611	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	5	57	theme	cellulose	906:914	arg1	set					889:891	each set	884:891	each set of replicate cellulose supplemented cultures originating from a sampled rumen environment	884:981	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	5	57	theme	cellulose	906:914	arg1	cellulose					906:914	replicate cellulose	896:914	replicate cellulose supplemented cultures originating from a sampled rumen environment	896:981	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	0	58	from	Identification	0:13	arg1	Bacteroidetes					64:76	Bacteroidetes	64:76	Bacteroidetes	64:76	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	0	58	from	Identification	0:13	arg1	Saccharibacteria					93:108	CANDIDATUS Saccharibacteria	82:108	CANDIDATUS Saccharibacteria	82:108	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	0	58	from	Identification	0:13	arg1	Firmicutes					52:61	Firmicutes	52:61	Firmicutes	52:61	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	8	59	theme	broad	1749:1753	arg1	range					1755:1759	a broad range	1747:1759	a broad range of microbial adaptations	1747:1784	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	6	60	theme	nucleotide	1229:1238	arg1	identity					1249:1256	high nucleotide sequence identity	1224:1256	high nucleotide sequence identity to currently defined bacterial species	1224:1295	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	3	61	theme	Operational	624:634	arg1	OTUs					653:656	OTUs	653:656	OTUs	653:656	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	3	61	theme	Operational	624:634	arg1	Units					646:650	252 Operational Taxonomic Units	620:650	252 Operational Taxonomic Units (OTUs)	620:657	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	8	62	theme	metabolic	1503:1511	arg1	s					1522:1522	the metabolic function(s)	1499:1523	the metabolic function(s) of each enriched OTU	1499:1544	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	63	theme	adaptations	1774:1784	arg1	range					1755:1759	a broad range	1747:1759	a broad range of microbial adaptations	1747:1784	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	64	theme	further	1445:1451	arg1	investigations					1453:1466	further investigations	1445:1466	further investigations	1445:1466	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	0	65	theme	Candidate	113:121	arg1	Utilizers					133:141	Candidate Cellulose Utilizers	113:141	Candidate Cellulose Utilizers from the Rumen of Beef Cows	113:169	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	4	66	from	samples	864:870	arg1	cultures					840:847	cellulose-supplemented cultures	817:847	cellulose-supplemented cultures from all rumen samples	817:870	Despite this high level of overlap, only one OTU was enriched in cellulose-supplemented cultures from all rumen samples.
29495256	4	67	theme	high	765:768	arg1	level					770:774	this high level	760:774	this high level of overlap	760:785	Despite this high level of overlap, only one OTU was enriched in cellulose-supplemented cultures from all rumen samples.
29495256	0	68	from	Rumen	152:156	arg1	Utilizers					133:141	Candidate Cellulose Utilizers	113:141	Candidate Cellulose Utilizers from the Rumen of Beef Cows	113:169	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	8	69	theme	structural	1813:1822	arg1	polysaccharides					1824:1838	plant structural polysaccharides	1807:1838	plant structural polysaccharides	1807:1838	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	8	70	theme	OTU	1542:1544	arg1	s					1522:1522	the metabolic function(s)	1499:1523	the metabolic function(s) of each enriched OTU	1499:1544	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	0	71	theme	Bacterial	29:37	arg1	Species					39:45	Uncultured Bacterial Species	18:45	Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria	18:108	Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.
29495256	1	72	theme	communities	290:300	arg1	activities					256:265	the metabolic activities	242:265	the metabolic activities of symbiotic microbial communities that reside in the rumen	242:325	The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen.
29495256	5	73	theme	sampled	957:963	arg1	environment					971:981	a sampled rumen environment	955:981	a sampled rumen environment	955:981	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	6	74	theme	defined	1271:1277	arg1	species					1289:1295	currently defined bacterial species	1261:1295	currently defined bacterial species	1261:1295	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	75	theme	enriched	1057:1064	arg1	OTUs					1066:1069	the seven most enriched OTUs	1042:1069	the seven most enriched OTUs	1042:1069	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	5	76	dep	cellulose	906:914	arg1	replicate					896:904	replicate	896:904	replicate	896:904	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	2	77	theme	microbial	370:378	arg1	ecosystem					380:388	this complex microbial ecosystem	357:388	this complex microbial ecosystem	357:388	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	2	78	theme	batch	409:413	arg1	approach					425:432	a selection-based batch culturing approach	391:432	a selection-based batch culturing approach	391:432	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	2	79	theme	cellulose-utilizing	465:483	arg1	consortia					495:503	candidate cellulose-utilizing bacterial consortia	455:503	candidate cellulose-utilizing bacterial consortia	455:503	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	2	80	theme	further	336:342	arg1	insight					344:350	further insight	336:350	further insight into this complex microbial ecosystem	336:388	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
29495256	8	81	theme	vast	1651:1654	arg1	distances					1669:1677	vast phylogenetic distances	1651:1677	vast phylogenetic distances	1651:1677	While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.
29495256	6	82	dep	utilizers	1128:1136	arg1	Fibrobactersuccinogenes					1168:1190	Fibrobactersuccinogenes	1168:1190	Fibrobactersuccinogenes	1168:1190	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	82	dep	utilizers	1128:1136	arg1	Ruminococcusflavefaciens					1139:1162	Ruminococcusflavefaciens	1139:1162	Ruminococcusflavefaciens	1139:1162	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	82	dep	utilizers	1128:1136	arg1	utilizers					1128:1136	well-established rumen cellulose utilizers	1095:1136	well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes)	1095:1191	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	5	83	theme	distinct	1003:1010	arg1	composition					1022:1032	a distinct bacterial composition	1001:1032	a distinct bacterial composition	1001:1032	Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition.
29495256	6	84	theme	cellulose	1118:1126	arg1	Fibrobactersuccinogenes					1168:1190	Fibrobactersuccinogenes	1168:1190	Fibrobactersuccinogenes	1168:1190	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	84	theme	cellulose	1118:1126	arg1	Ruminococcusflavefaciens					1139:1162	Ruminococcusflavefaciens	1139:1162	Ruminococcusflavefaciens	1139:1162	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	6	84	theme	cellulose	1118:1126	arg1	utilizers					1128:1136	well-established rumen cellulose utilizers	1095:1136	well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes)	1095:1191	Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcusflavefaciens and Fibrobactersuccinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species.
29495256	3	85	theme	rRNA	703:706	arg1	sequences					713:721	bacterial 16S rRNA gene sequences	689:721	bacterial 16S rRNA gene sequences in their respective samples	689:749	Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples.
29495256	2	86	theme	complex	362:368	arg1	ecosystem					380:388	this complex microbial ecosystem	357:388	this complex microbial ecosystem	357:388	To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia.
31787385	0	0	theme	Aeribacillus	109:120	arg1	SL-1					138:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	8	1	theme	great	1331:1335	arg1	potential					1337:1345	great potential	1331:1345	great potential for applications in high-temperature bioremediation	1331:1397	Thus, the bioemulsifier-producing strain SL-1 has great potential for applications in high-temperature bioremediation.
31787385	6	2	theme	Chemical	1008:1015	arg1	studies					1029:1035	Chemical composition studies	1008:1035	Chemical composition studies	1008:1035	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	0	3	theme	bioemulsifier-producing	85:107	arg1	SL-1					138:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	2	4	theme	Aeribacillus	408:419	arg1	SL-1					430:433	the thermophilic strain Aeribacillus pallidus SL-1	384:433	the thermophilic strain Aeribacillus pallidus SL-1	384:433	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	2	5	from	oil	618:620	arg1	<C17					575:578	<C17	575:578	<C17	575:578	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	2	5	from	oil	618:620	arg1	n-alkanes					564:572	short-chain n-alkanes	552:572	short-chain n-alkanes (<C17)	552:579	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	2	5	from	oil	618:620	arg1	hydrocarbons					594:605	aromatic hydrocarbons	585:605	aromatic hydrocarbons from crude oil	585:620	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	0	6	theme	strain	131:136	arg1	SL-1					138:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	6	7	theme	emulsifying	1168:1178	arg1	proteins					1114:1121	proteins	1114:1121	proteins (13.1%)	1114:1129	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	6	7	theme	emulsifying	1168:1178	arg1	proteins					1144:1151	proteins	1144:1151	proteins	1144:1151	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	6	7	theme	emulsifying	1168:1178	arg1	substrates					1191:1200	the major emulsifying functional substrates	1158:1200	the major emulsifying functional substrates	1158:1200	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	0	8	theme	pallidus	122:129	arg1	SL-1					138:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	5	9	theme	wide	968:971	arg1	range					973:977	a wide range	966:977	a wide range of environmental conditions	966:1005	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	2	10	dep	Aeribacillus	408:419	arg1	pallidus					421:428	pallidus	421:428	pallidus	421:428	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	1	11	theme	oil	322:324	arg1	recovery					326:333	oil recovery	322:333	oil recovery from high-temperature reservoirs	322:366	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	4	12	from	60 °C	843:847	arg1	days					835:838	5 days	833:838	5 days at 60 °C	833:847	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	5	13	with	glycoprotein	915:926	arg1	activity					952:959	stable emulsifying activity	933:959	stable emulsifying activity over a wide range of environmental conditions	933:1005	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	1	14	theme	suitable	218:225	arg1	strategy					227:234	a suitable strategy	216:234	a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs	216:366	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	1	14	theme	suitable	218:225	arg1	utilization					148:158	The utilization	144:158	The utilization of thermophilic hydrocarbon-degrading microorganisms	144:211	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	1	15	from	reservoirs	357:366	arg1	recovery					326:333	oil recovery	322:333	oil recovery from high-temperature reservoirs	322:366	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	6	16	dep	consisted	1073:1081	arg1	%					1107:1107	65.6%	1103:1107	65.6%	1103:1107	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	2	17	theme	Strain	504:509	arg1	SL-1					511:514	60 °C. Strain SL-1	497:514	60 °C. Strain SL-1	497:514	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	5	18	theme	stable	933:938	arg1	activity					952:959	stable emulsifying activity	933:959	stable emulsifying activity over a wide range of environmental conditions	933:1005	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	2	19	theme	60 °C.	497:502	arg1	SL-1					511:514	60 °C. Strain SL-1	497:514	60 °C. Strain SL-1	497:514	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	3	20	theme	highest	627:633	arg1	source					714:719	sole carbon source	702:719	sole carbon source	702:719	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	3	20	theme	highest	627:633	arg1	rate					647:650	The highest degradation rate	623:650	The highest degradation rate of 84%	623:657	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	3	21	theme	sole	702:705	arg1	source					714:719	sole carbon source	702:719	sole carbon source	702:719	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	3	21	theme	sole	702:705	arg1	rate					647:650	The highest degradation rate	623:650	The highest degradation rate of 84%	623:657	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	2	22	theme	crude	612:616	arg1	oil					618:620	crude oil	612:620	crude oil	612:620	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	8	23	theme	strain	1315:1320	arg1	SL-1					1322:1325	the bioemulsifier-producing strain SL-1	1287:1325	the bioemulsifier-producing strain SL-1	1287:1325	Thus, the bioemulsifier-producing strain SL-1 has great potential for applications in high-temperature bioremediation.
31787385	0	24	theme	aliphatic	18:26	arg1	hydrocarbons					52:63	aliphatic and polycyclic aromatic hydrocarbons	18:63	aliphatic and polycyclic aromatic hydrocarbons	18:63	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	1	25	theme	high-temperature	340:355	arg1	reservoirs					357:366	high-temperature reservoirs	340:366	high-temperature reservoirs	340:366	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	5	26	theme	emulsifying	940:950	arg1	activity					952:959	stable emulsifying activity	933:959	stable emulsifying activity over a wide range of environmental conditions	933:1005	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	4	27	theme	phenanthrene	774:785	arg1	pyrene					809:814	pyrene	809:814	pyrene (50 mg/l)	809:824	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	27	theme	phenanthrene	774:785	arg1	200 mg/l					788:795	200 mg/l	788:795	200 mg/l	788:795	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	27	theme	phenanthrene	774:785	arg1	50 mg/l					817:823	50 mg/l	817:823	50 mg/l	817:823	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	27	theme	phenanthrene	774:785	arg1	%					769:769	80%	767:769	80% of phenanthrene (200 mg/l)	767:796	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	27	theme	phenanthrene	774:785	arg1	phenanthrene					774:785	phenanthrene	774:785	phenanthrene (200 mg/l)	774:796	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	27	theme	phenanthrene	774:785	arg1	%					804:804	50%	802:804	50% of pyrene (50 mg/l)	802:824	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	2	28	theme	oil	481:483	arg1	biodegradation					457:470	the biodegradation	453:470	the biodegradation of crude oil and PAHs	453:492	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	0	29	theme	aromatic	43:50	arg1	hydrocarbons					52:63	aliphatic and polycyclic aromatic hydrocarbons	18:63	aliphatic and polycyclic aromatic hydrocarbons	18:63	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	2	30	theme	crude	475:479	arg1	oil					481:483	crude oil	475:483	crude oil	475:483	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	6	31	theme	functional	1180:1189	arg1	proteins					1114:1121	proteins	1114:1121	proteins (13.1%)	1114:1129	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	6	31	theme	functional	1180:1189	arg1	proteins					1144:1151	proteins	1144:1151	proteins	1144:1151	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	6	31	theme	functional	1180:1189	arg1	substrates					1191:1200	the major emulsifying functional substrates	1158:1200	the major emulsifying functional substrates	1158:1200	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	1	32	theme	petroleum	268:276	arg1	hydrocarbons					278:289	petroleum hydrocarbons	268:289	petroleum hydrocarbons	268:289	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	0	33	theme	polycyclic	32:41	arg1	hydrocarbons					52:63	aliphatic and polycyclic aromatic hydrocarbons	18:63	aliphatic and polycyclic aromatic hydrocarbons	18:63	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	2	34	theme	aromatic	585:592	arg1	hydrocarbons					594:605	aromatic hydrocarbons	585:605	aromatic hydrocarbons from crude oil	585:620	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	3	35	theme	1000 mg/l	677:685	arg1	naphthalene					687:697	1000 mg/l naphthalene	677:697	1000 mg/l naphthalene	677:697	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	5	36	gly	glycoprotein	915:926	arg1	SL-bioemulsifier					854:869	The SL-bioemulsifier	850:869	The SL-bioemulsifier produced by strain SL-1	850:893	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	5	36	gly	glycoprotein	915:926	arg1	glycoprotein					915:926	a glycoprotein	913:926	a glycoprotein with stable emulsifying activity over a wide range of environmental conditions	913:1005	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	1	37	theme	hydrocarbons	278:289	arg1	biodegradation					250:263	biodegradation	250:263	biodegradation of petroleum hydrocarbons and PAHs	250:298	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	5	38	theme	strain	883:888	arg1	SL-1					890:893	strain SL-1	883:893	strain SL-1	883:893	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	3	39	theme	degradation	635:645	arg1	source					714:719	sole carbon source	702:719	sole carbon source	702:719	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	3	39	theme	degradation	635:645	arg1	rate					647:650	The highest degradation rate	623:650	The highest degradation rate of 84%	623:657	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	8	40	theme	high-temperature	1367:1382	arg1	bioremediation					1384:1397	high-temperature bioremediation	1367:1397	high-temperature bioremediation	1367:1397	Thus, the bioemulsifier-producing strain SL-1 has great potential for applications in high-temperature bioremediation.
31787385	2	41	theme	strain	401:406	arg1	SL-1					430:433	the thermophilic strain Aeribacillus pallidus SL-1	384:433	the thermophilic strain Aeribacillus pallidus SL-1	384:433	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	0	42	theme	hydrocarbons	52:63	arg1	Biodegradation					0:13	Biodegradation	0:13	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.	0:142	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	6	43	theme	major	1162:1166	arg1	proteins					1114:1121	proteins	1114:1121	proteins (13.1%)	1114:1129	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	6	43	theme	major	1162:1166	arg1	proteins					1144:1151	proteins	1144:1151	proteins	1144:1151	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	6	43	theme	major	1162:1166	arg1	substrates					1191:1200	the major emulsifying functional substrates	1158:1200	the major emulsifying functional substrates	1158:1200	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31787385	8	44	contain	has	1327:1329	arg1	SL-1					1322:1325	the bioemulsifier-producing strain SL-1	1287:1325	the bioemulsifier-producing strain SL-1	1287:1325	Thus, the bioemulsifier-producing strain SL-1 has great potential for applications in high-temperature bioremediation.
31787385	8	44	contain	has	1327:1329	arg2	potential					1337:1345	great potential	1331:1345	great potential for applications in high-temperature bioremediation	1331:1397	Thus, the bioemulsifier-producing strain SL-1 has great potential for applications in high-temperature bioremediation.
31787385	7	45	theme	PAHs	1275:1278	arg1	solubility					1261:1270	the solubility	1257:1270	the solubility of PAHs	1257:1278	Furthermore, the SL-bioemulsifier was able to enhance the solubility of PAHs.
31787385	2	46	theme	thermophilic	388:399	arg1	SL-1					430:433	the thermophilic strain Aeribacillus pallidus SL-1	384:433	the thermophilic strain Aeribacillus pallidus SL-1	384:433	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	4	47	theme	pyrene	809:814	arg1	pyrene					809:814	pyrene	809:814	pyrene (50 mg/l)	809:824	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	47	theme	pyrene	809:814	arg1	200 mg/l					788:795	200 mg/l	788:795	200 mg/l	788:795	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	47	theme	pyrene	809:814	arg1	50 mg/l					817:823	50 mg/l	817:823	50 mg/l	817:823	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	47	theme	pyrene	809:814	arg1	%					769:769	80%	767:769	80% of phenanthrene (200 mg/l)	767:796	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	47	theme	pyrene	809:814	arg1	phenanthrene					774:785	phenanthrene	774:785	phenanthrene (200 mg/l)	774:796	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	4	47	theme	pyrene	809:814	arg1	%					804:804	50%	802:804	50% of pyrene (50 mg/l)	802:824	Additionally, the strain was able to degrade 80% of phenanthrene (200 mg/l) and 50% of pyrene (50 mg/l) within 5 days at 60 °C.
31787385	5	48	theme	environmental	982:994	arg1	conditions					996:1005	environmental conditions	982:1005	environmental conditions	982:1005	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	8	49	theme	bioemulsifier-producing	1291:1313	arg1	SL-1					1322:1325	the bioemulsifier-producing strain SL-1	1287:1325	the bioemulsifier-producing strain SL-1	1287:1325	Thus, the bioemulsifier-producing strain SL-1 has great potential for applications in high-temperature bioremediation.
31787385	8	50	from	applications	1351:1362	arg1	bioremediation					1384:1397	high-temperature bioremediation	1367:1397	high-temperature bioremediation	1367:1397	Thus, the bioemulsifier-producing strain SL-1 has great potential for applications in high-temperature bioremediation.
31787385	3	51	theme	carbon	707:712	arg1	source					714:719	sole carbon source	702:719	sole carbon source	702:719	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	3	51	theme	carbon	707:712	arg1	rate					647:650	The highest degradation rate	623:650	The highest degradation rate of 84%	623:657	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	5	52	theme	conditions	996:1005	arg1	range					973:977	a wide range	966:977	a wide range of environmental conditions	966:1005	The SL-bioemulsifier produced by strain SL-1 was identified as a glycoprotein with stable emulsifying activity over a wide range of environmental conditions.
31787385	1	53	theme	thermophilic	163:174	arg1	microorganisms					198:211	thermophilic hydrocarbon-degrading microorganisms	163:211	thermophilic hydrocarbon-degrading microorganisms	163:211	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	1	54	theme	PAHs	295:298	arg1	biodegradation					250:263	biodegradation	250:263	biodegradation of petroleum hydrocarbons and PAHs	250:298	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	0	55	theme	thermophilic	72:83	arg1	SL-1					138:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1	68:141	Biodegradation of aliphatic and polycyclic aromatic hydrocarbons by the thermophilic bioemulsifier-producing Aeribacillus pallidus strain SL-1.
31787385	3	56	theme	%	657:657	arg1	source					714:719	sole carbon source	702:719	sole carbon source	702:719	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	3	56	theme	%	657:657	arg1	rate					647:650	The highest degradation rate	623:650	The highest degradation rate of 84%	623:657	The highest degradation rate of 84% was obtained with 1000 mg/l naphthalene as sole carbon source.
31787385	1	57	theme	hydrocarbon-degrading	176:196	arg1	microorganisms					198:211	thermophilic hydrocarbon-degrading microorganisms	163:211	thermophilic hydrocarbon-degrading microorganisms	163:211	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	2	58	theme	short-chain	552:562	arg1	<C17					575:578	<C17	575:578	<C17	575:578	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	2	58	theme	short-chain	552:562	arg1	n-alkanes					564:572	short-chain n-alkanes	552:572	short-chain n-alkanes (<C17)	552:579	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	2	59	theme	PAHs	489:492	arg1	biodegradation					457:470	the biodegradation	453:470	the biodegradation of crude oil and PAHs	453:492	In this study, the thermophilic strain Aeribacillus pallidus SL-1 was evaluated for the biodegradation of crude oil and PAHs at 60 °C. Strain SL-1 was found to preferentially degrade short-chain n-alkanes (<C17) and aromatic hydrocarbons from crude oil.
31787385	1	60	theme	microorganisms	198:211	arg1	utilization					148:158	The utilization	144:158	The utilization of thermophilic hydrocarbon-degrading microorganisms	144:211	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	1	60	theme	microorganisms	198:211	arg1	strategy					227:234	a suitable strategy	216:234	a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs	216:366	The utilization of thermophilic hydrocarbon-degrading microorganisms is a suitable strategy for improving biodegradation of petroleum hydrocarbons and PAHs, as well as enhancing oil recovery from high-temperature reservoirs.
31787385	6	61	theme	composition	1017:1027	arg1	studies					1029:1035	Chemical composition studies	1008:1035	Chemical composition studies	1008:1035	Chemical composition studies exhibited that the SL-bioemulsifier consisted of polysaccharides (65.6%) and proteins (13.1%), among them, proteins were the major emulsifying functional substrates.
31560681	10	0	theme	interventions	1580:1592	arg1	potential					1559:1567	the potential	1555:1567	the potential of dietary interventions to alleviate the impact of cryptosporidiosis	1555:1637	These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.
31560681	8	1	from	impact	1231:1236	arg1	proliferation					1258:1270	parasite proliferation	1249:1270	parasite proliferation	1249:1270	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	8	2	dep	observations	1209:1220	arg1	mediated					1275:1282	mediated	1275:1282	mediated	1275:1282	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	10	3	theme	dietary	1572:1578	arg1	interventions					1580:1592	dietary interventions	1572:1592	dietary interventions	1572:1592	These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.
31560681	6	4	theme	fewer	929:933	arg1	oocysts					935:941	significantly fewer oocysts	915:941	significantly fewer oocysts	915:941	Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts.
31560681	3	5	theme	oocyst	544:549	arg1	output					551:556	oocyst output	544:556	oocyst output	544:556	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	9	6	theme	metabolic	1446:1454	arg1	dependence					1456:1465	the metabolic dependence	1442:1465	the metabolic dependence of intracellular stages of the parasite on the host cell	1442:1522	This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell.
31560681	10	7	theme	cryptosporidiosis	1621:1637	arg1	impact					1611:1616	the impact	1607:1616	the impact of cryptosporidiosis	1607:1637	These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.
31560681	7	8	theme	plant	986:990	arg1	polysaccharides					992:1006	no plant polysaccharides	983:1006	no plant polysaccharides	983:1006	The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria.
31560681	8	9	theme	certain	1379:1385	arg1	metabolites					1387:1397	certain metabolites	1379:1397	certain metabolites	1379:1397	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	1	10	theme	intracellular	269:281	arg1	proliferation					283:295	the intracellular proliferation	265:295	the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse	265:349	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	10	11	from	risk	1667:1670	arg1	infants					1656:1662	infants	1656:1662	infants at risk of recurrent enteric infections	1656:1702	These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.
31560681	7	12	theme	mice	968:971	arg1	microbiota					954:963	The fecal microbiota	944:963	The fecal microbiota of mice consuming no plant polysaccharides	944:1006	The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria.
31560681	8	13	theme	metabolic	1301:1309	arg1	activity					1311:1318	the metabolic activity	1297:1318	the metabolic activity of the anaerobic microbiota	1297:1346	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	8	14	theme	bacterial	1089:1097	arg1	metabolites					1099:1109	bacterial metabolites	1089:1109	bacterial metabolites	1089:1109	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	3	15	theme	RNA	508:510	arg1	amplicons					512:520	16S ribosomal RNA amplicons	494:520	16S ribosomal RNA amplicons	494:520	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	10	16	theme	infections	1693:1702	arg1	risk					1667:1670	risk	1667:1670	risk of recurrent enteric infections	1667:1702	These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.
31560681	3	17	theme	High-throughput	464:478	arg1	sequencing					480:489	High-throughput sequencing	464:489	High-throughput sequencing of 16S ribosomal RNA amplicons	464:520	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	9	18	theme	parasite	1498:1505	arg1	stages					1484:1489	intracellular stages	1470:1489	intracellular stages of the parasite	1470:1505	This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell.
31560681	6	19	theme	human	888:892	arg1	consumption					894:904	human consumption	888:904	human consumption	888:904	Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts.
31560681	8	20	from	effect	1369:1374	arg1	host					1406:1409	the host	1402:1409	the host	1402:1409	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	8	21	theme	metabolites	1387:1397	arg1	effect					1369:1374	the effect	1365:1374	the effect of certain metabolites on the host	1365:1409	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	1	22	theme	severe	178:183	arg1	cryptosporidiosis					185:201	more severe cryptosporidiosis	173:201	more severe cryptosporidiosis	173:201	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	6	23	with	Consistent	814:823	arg1	observations					836:847	these observations	830:847	these observations	830:847	Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts.
31560681	2	24	theme	parasite	395:402	arg1	multiplication					404:417	parasite multiplication	395:417	parasite multiplication	395:417	Mice were orally infected with oocysts and parasite multiplication measured by quantifying fecal oocyst output.
31560681	3	25	theme	intestinal	600:609	arg1	microbiota					611:620	the intestinal microbiota	596:620	the intestinal microbiota	596:620	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	10	26	theme	enteric	1685:1691	arg1	infections					1693:1702	recurrent enteric infections	1675:1702	recurrent enteric infections	1675:1702	These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.
31560681	0	27	theme	fiber	23:27	arg1	Deprivation					0:10	Deprivation	0:10	Deprivation of dietary fiber	0:27	Deprivation of dietary fiber enhances susceptibility of mice to cryptosporidiosis.
31560681	8	28	theme	important	1119:1127	arg1	role					1129:1132	an important role	1116:1132	an important role	1116:1132	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	7	29	theme	fecal	948:952	arg1	microbiota					954:963	The fecal microbiota	944:963	The fecal microbiota of mice consuming no plant polysaccharides	944:1006	The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria.
31560681	1	30	theme	initial	96:102	arg1	observations					104:115	our initial observations	92:115	our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis	92:201	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	9	31	theme	intracellular	1470:1482	arg1	stages					1484:1489	intracellular stages	1470:1489	intracellular stages of the parasite	1470:1505	This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell.
31560681	2	32	theme	oocyst	449:454	arg1	output					456:461	fecal oocyst output	443:461	fecal oocyst output	443:461	Mice were orally infected with oocysts and parasite multiplication measured by quantifying fecal oocyst output.
31560681	0	33	theme	dietary	15:21	arg1	fiber					23:27	dietary fiber	15:27	dietary fiber	15:27	Deprivation of dietary fiber enhances susceptibility of mice to cryptosporidiosis.
31560681	1	34	theme	parvum	316:321	arg1	proliferation					283:295	the intracellular proliferation	265:295	the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse	265:349	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	1	35	from	proliferation	283:295	arg1	mouse					345:349	the mouse	341:349	the mouse	341:349	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	2	36	theme	fecal	443:447	arg1	output					456:461	fecal oocyst output	443:461	fecal oocyst output	443:461	Mice were orally infected with oocysts and parasite multiplication measured by quantifying fecal oocyst output.
31560681	10	37	theme	recurrent	1675:1683	arg1	infections					1693:1702	recurrent enteric infections	1675:1702	recurrent enteric infections	1675:1702	These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.
31560681	6	38	theme	product	871:877	arg1	sold					879:882	a prebiotic product sold	859:882	a prebiotic product sold for human consumption	859:904	Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts.
31560681	8	39	theme	diet	1241:1244	arg1	impact					1231:1236	the impact	1227:1236	the impact of diet on parasite proliferation	1227:1270	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	6	40	theme	prebiotic	861:869	arg1	sold					879:882	a prebiotic product sold	859:882	a prebiotic product sold for human consumption	859:904	Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts.
31560681	4	41	dep	fiber	659:663	arg1	inulin					688:693	inulin	688:693	inulin	688:693	On average, mice fed a diet without fiber (cellulose, pectin and inulin) developed more severe infections.
31560681	4	41	dep	fiber	659:663	arg1	pectin					677:682	pectin	677:682	pectin	677:682	On average, mice fed a diet without fiber (cellulose, pectin and inulin) developed more severe infections.
31560681	4	41	dep	fiber	659:663	arg1	cellulose					666:674	cellulose	666:674	cellulose	666:674	On average, mice fed a diet without fiber (cellulose, pectin and inulin) developed more severe infections.
31560681	7	42	theme	relative	1037:1044	arg1	abundance					1046:1054	a lower relative abundance	1029:1054	a lower relative abundance of Bacteroidetes bacteria	1029:1080	The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria.
31560681	3	43	theme	16S	494:496	arg1	amplicons					512:520	16S ribosomal RNA amplicons	494:520	16S ribosomal RNA amplicons	494:520	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	0	44	theme	mice	56:59	arg1	susceptibility					38:51	susceptibility	38:51	susceptibility of mice to cryptosporidiosis	38:80	Deprivation of dietary fiber enhances susceptibility of mice to cryptosporidiosis.
31560681	1	45	theme	tyzzeri	330:336	arg1	proliferation					283:295	the intracellular proliferation	265:295	the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse	265:349	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	7	46	theme	bacteria	1073:1080	arg1	abundance					1046:1054	a lower relative abundance	1029:1054	a lower relative abundance of Bacteroidetes bacteria	1029:1080	The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria.
31560681	8	47	theme	enterocytes	1166:1176	arg1	physiology					1141:1150	the physiology	1137:1150	the physiology of intestinal enterocytes	1137:1176	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	3	48	theme	microbiota	611:620	arg1	composition					581:591	the composition	577:591	the composition of the intestinal microbiota	577:620	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	1	49	from	impact	224:229	arg1	proliferation					283:295	the intracellular proliferation	265:295	the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse	265:349	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	8	50	theme	anaerobic	1327:1335	arg1	microbiota					1337:1346	the anaerobic microbiota	1323:1346	the anaerobic microbiota	1323:1346	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	8	51	theme	parasite	1249:1256	arg1	proliferation					1258:1270	parasite proliferation	1249:1270	parasite proliferation	1249:1270	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	9	52	from	dependence	1456:1465	arg1	cell					1519:1522	the host cell	1510:1522	the host cell	1510:1522	This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell.
31560681	3	53	used	used	526:529	arg2	sequencing					480:489	High-throughput sequencing	464:489	High-throughput sequencing of 16S ribosomal RNA amplicons	464:520	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	4	54	theme	severe	711:716	arg1	infections					718:727	more severe infections	706:727	more severe infections	706:727	On average, mice fed a diet without fiber (cellulose, pectin and inulin) developed more severe infections.
31560681	8	55	theme	intestinal	1155:1164	arg1	enterocytes					1166:1176	intestinal enterocytes	1155:1176	intestinal enterocytes	1155:1176	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	3	56	theme	amplicons	512:520	arg1	sequencing					480:489	High-throughput sequencing	464:489	High-throughput sequencing of 16S ribosomal RNA amplicons	464:520	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	7	57	theme	Bacteroidetes	1059:1071	arg1	bacteria					1073:1080	Bacteroidetes bacteria	1059:1080	Bacteroidetes bacteria	1059:1080	The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria.
31560681	9	58	with	consistent	1426:1435	arg1	dependence					1456:1465	the metabolic dependence	1442:1465	the metabolic dependence of intracellular stages of the parasite on the host cell	1442:1522	This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell.
31560681	8	59	theme	microbiota	1337:1346	arg1	activity					1311:1318	the metabolic activity	1297:1318	the metabolic activity of the anaerobic microbiota	1297:1346	Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host.
31560681	1	60	theme	other	234:238	arg1	interventions					248:260	other dietary interventions	234:260	other dietary interventions	234:260	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	9	61	theme	host	1514:1517	arg1	cell					1519:1522	the host cell	1510:1522	the host cell	1510:1522	This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell.
31560681	3	62	theme	ribosomal	498:506	arg1	amplicons					512:520	16S ribosomal RNA amplicons	494:520	16S ribosomal RNA amplicons	494:520	High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota.
31560681	9	63	theme	stages	1484:1489	arg1	dependence					1456:1465	the metabolic dependence	1442:1465	the metabolic dependence of intracellular stages of the parasite on the host cell	1442:1522	This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell.
31560681	1	64	theme	dietary	240:246	arg1	interventions					248:260	other dietary interventions	234:260	other dietary interventions	234:260	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	5	65	theme	fecal	796:800	arg1	microbiota					802:811	the fecal microbiota	792:811	the fecal microbiota	792:811	As expected, a diet without fibers also significantly altered the fecal microbiota.
31560681	1	66	theme	probiotic	147:155	arg1	product					157:163	a probiotic product	145:163	a probiotic product	145:163	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31560681	1	67	theme	interventions	248:260	arg1	impact					224:229	the impact	220:229	the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse	220:349	Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse.
31413280	8	0	theme	RPS-reactive	1258:1269	arg1	serotype					1271:1278	the type 4 RPS-reactive serotype	1247:1278	the type 4 RPS-reactive serotype	1247:1278	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	8	0	theme	RPS-reactive	1258:1269	arg1	absent					1284:1289	absent	1284:1289	absent	1284:1289	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	7	1	theme	coaggregation-mediating	1081:1103	arg1	polysaccharides					1141:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides	1077:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	1077:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	7	1	theme	coaggregation-mediating	1081:1103	arg1	RPS					1158:1160	RPS	1158:1160	RPS	1158:1160	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	1	2	theme	initial	153:159	arg1	colonization					171:182	initial bacterial colonization	153:182	initial bacterial colonization	153:182	This study evaluated the impact of mechanically stimulated saliva on initial bacterial colonization.
31413280	4	3	theme	stimulated	613:622	arg1	saliva					624:629	stimulated saliva	613:629	stimulated saliva	613:629	In vitro experiments showed that bacterial binding to proteins from stimulated saliva was lower than that to proteins from unstimulated saliva.
31413280	4	4	theme	In	545:546	arg1	experiments					554:564	In vitro experiments	545:564	In vitro experiments	545:564	In vitro experiments showed that bacterial binding to proteins from stimulated saliva was lower than that to proteins from unstimulated saliva.
31413280	1	5	theme	bacterial	161:169	arg1	colonization					171:182	initial bacterial colonization	153:182	initial bacterial colonization	153:182	This study evaluated the impact of mechanically stimulated saliva on initial bacterial colonization.
31413280	7	6	theme	streptococcal	1105:1117	arg1	polysaccharides					1141:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides	1077:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	1077:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	7	6	theme	streptococcal	1105:1117	arg1	RPS					1158:1160	RPS	1158:1160	RPS	1158:1160	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	3	7	theme	in	381:382	arg1	biofilm					389:395	in vivo biofilm	381:395	in vivo biofilm	381:395	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	0	8	from	Effect	0:5	arg1	formation					73:81	initial human dental biofilm formation	44:81	initial human dental biofilm formation	44:81	Effect of mechanically stimulated saliva on initial human dental biofilm formation.
31413280	10	9	theme	bacterial	1511:1519	arg1	patterns					1529:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	6	10	theme	chewing-related	859:873	arg1	increase					875:882	a consistent chewing-related increase	846:882	a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii	846:951	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	7	11	theme	multi-species	1013:1025	arg1	colonies					1027:1034	multi-species colonies	1013:1034	multi-species colonies	1013:1034	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	4	12	from	saliva	624:629	arg1	proteins					599:606	proteins	599:606	proteins from stimulated saliva	599:629	In vitro experiments showed that bacterial binding to proteins from stimulated saliva was lower than that to proteins from unstimulated saliva.
31413280	2	13	theme	labeled	295:301	arg1	bacteria					303:310	labeled bacteria	295:310	labeled bacteria	295:310	Interaction between oral bacteria and both unstimulated and stimulated saliva was examined in vitro by laying labeled bacteria over SDS-PAGE-separated salivary proteins.
31413280	6	14	theme	consistent	848:857	arg1	increase					875:882	a consistent chewing-related increase	846:882	a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii	846:951	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	3	15	theme	enamel	531:536	arg1	chips					538:542	retrievable enamel chips	519:542	retrievable enamel chips	519:542	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	3	16	theme	chewing	370:376	arg1	effects					359:365	The effects	355:365	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement	355:443	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	7	17	theme	different	1054:1062	arg1	serotypes					1064:1072	different serotypes	1054:1072	different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	1054:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	10	18	theme	binding	1521:1527	arg1	patterns					1529:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	8	19	theme	bacterial	1179:1187	arg1	colonization					1189:1200	bacterial colonization	1179:1200	bacterial colonization	1179:1200	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	10	20	theme	multiple	1563:1570	arg1	stimuli					1583:1589	multiple orosensory stimuli	1563:1589	multiple orosensory stimuli	1563:1589	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	8	21	from	Differences	1164:1174	arg1	colonization					1189:1200	bacterial colonization	1179:1200	bacterial colonization	1179:1200	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	3	22	theme	microbial	398:406	arg1	composition					408:418	microbial composition	398:418	microbial composition	398:418	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	3	23	contain	containing	508:517	arg2	chips					538:542	retrievable enamel chips	519:542	retrievable enamel chips	519:542	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	3	23	contain	containing	508:517	arg1	stent					502:506	an intraoral stent	489:506	an intraoral stent containing retrievable enamel chips	489:542	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	10	24	theme	bacterial	1609:1617	arg1	colonization					1619:1630	oral bacterial colonization	1604:1630	oral bacterial colonization of tooth surfaces	1604:1648	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	7	25	theme	cells	1040:1044	arg1	presence					1001:1008	the presence	997:1008	the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	997:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	10	26	dep	in	1503:1504	arg1	vivo					1506:1509	vivo	1506:1509	vivo	1506:1509	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	6	27	from	increase	875:882	arg1	binding					891:897	the binding	887:897	the binding of Streptococcus anginosus and Streptococcus gordonii	887:951	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	10	28	theme	orosensory	1572:1581	arg1	stimuli					1583:1589	multiple orosensory stimuli	1563:1589	multiple orosensory stimuli	1563:1589	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	8	29	from	absent	1284:1289	arg1	volunteer					1298:1306	one volunteer	1294:1306	one volunteer	1294:1306	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	1	30	from	impact	109:114	arg1	colonization					171:182	initial bacterial colonization	153:182	initial bacterial colonization	153:182	This study evaluated the impact of mechanically stimulated saliva on initial bacterial colonization.
31413280	2	31	theme	salivary	336:343	arg1	proteins					345:352	SDS-PAGE-separated salivary proteins	317:352	SDS-PAGE-separated salivary proteins	317:352	Interaction between oral bacteria and both unstimulated and stimulated saliva was examined in vitro by laying labeled bacteria over SDS-PAGE-separated salivary proteins.
31413280	4	32	from	saliva	681:686	arg1	proteins					654:661	proteins	654:661	proteins from unstimulated saliva	654:686	In vitro experiments showed that bacterial binding to proteins from stimulated saliva was lower than that to proteins from unstimulated saliva.
31413280	0	33	theme	stimulated	23:32	arg1	saliva					34:39	mechanically stimulated saliva	10:39	mechanically stimulated saliva	10:39	Effect of mechanically stimulated saliva on initial human dental biofilm formation.
31413280	4	34	theme	bacterial	578:586	arg1	binding					588:594	bacterial binding	578:594	bacterial binding to proteins from stimulated saliva	578:629	In vitro experiments showed that bacterial binding to proteins from stimulated saliva was lower than that to proteins from unstimulated saliva.
31413280	7	35	theme	colonies	1027:1034	arg1	presence					1001:1008	the presence	997:1008	the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	997:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	2	36	theme	SDS-PAGE-separated	317:334	arg1	proteins					345:352	SDS-PAGE-separated salivary proteins	317:352	SDS-PAGE-separated salivary proteins	317:352	Interaction between oral bacteria and both unstimulated and stimulated saliva was examined in vitro by laying labeled bacteria over SDS-PAGE-separated salivary proteins.
31413280	10	37	theme	oral	1604:1607	arg1	colonization					1619:1630	oral bacterial colonization	1604:1630	oral bacterial colonization of tooth surfaces	1604:1648	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	7	38	theme	cell-surface	1119:1130	arg1	polysaccharides					1141:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides	1077:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	1077:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	7	38	theme	cell-surface	1119:1130	arg1	RPS					1158:1160	RPS	1158:1160	RPS	1158:1160	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	7	39	theme	receptor	1132:1139	arg1	polysaccharides					1141:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides	1077:1155	the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	1077:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	7	39	theme	receptor	1132:1139	arg1	RPS					1158:1160	RPS	1158:1160	RPS	1158:1160	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	6	40	theme	Streptococcus	930:942	arg1	binding					891:897	the binding	887:897	the binding of Streptococcus anginosus and Streptococcus gordonii	887:951	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	10	41	dep	in	1490:1491	arg1	vitro					1493:1497	vitro	1493:1497	vitro	1493:1497	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	10	42	theme	inter-individual	1454:1469	arg1	variations					1471:1480	inter-individual variations	1454:1480	inter-individual variations in both in vitro and in vivo bacterial binding patterns	1454:1536	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	3	43	theme	spatial	425:431	arg1	arrangement					433:443	spatial arrangement	425:443	spatial arrangement	425:443	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	10	44	theme	surfaces	1641:1648	arg1	colonization					1619:1630	oral bacterial colonization	1604:1630	oral bacterial colonization of tooth surfaces	1604:1648	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	10	45	theme	in	1503:1504	arg1	patterns					1529:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	10	46	theme	data	1427:1430	arg1	analysis					1411:1418	analysis	1411:1418	analysis of the data obtained	1411:1439	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	3	47	theme	human	466:470	arg1	volunteers					472:481	two human volunteers	462:481	two human volunteers using an intraoral stent containing retrievable enamel chips	462:542	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	0	48	theme	saliva	34:39	arg1	Effect					0:5	Effect	0:5	Effect of mechanically stimulated saliva on initial human dental biofilm formation.	0:82	Effect of mechanically stimulated saliva on initial human dental biofilm formation.
31413280	4	49	dep	In	545:546	arg1	vitro					548:552	vitro	548:552	vitro	548:552	In vitro experiments showed that bacterial binding to proteins from stimulated saliva was lower than that to proteins from unstimulated saliva.
31413280	10	50	theme	tooth	1635:1639	arg1	surfaces					1641:1648	tooth surfaces	1635:1648	tooth surfaces	1635:1648	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	6	51	theme	anginosus	916:924	arg1	binding					891:897	the binding	887:897	the binding of Streptococcus anginosus and Streptococcus gordonii	887:951	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	2	52	theme	stimulated	245:254	arg1	saliva					256:261	both unstimulated and stimulated saliva	223:261	both unstimulated and stimulated saliva	223:261	Interaction between oral bacteria and both unstimulated and stimulated saliva was examined in vitro by laying labeled bacteria over SDS-PAGE-separated salivary proteins.
31413280	10	53	theme	in	1490:1491	arg1	patterns					1529:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	4	54	theme	unstimulated	668:679	arg1	saliva					681:686	unstimulated saliva	668:686	unstimulated saliva	668:686	In vitro experiments showed that bacterial binding to proteins from stimulated saliva was lower than that to proteins from unstimulated saliva.
31413280	0	55	theme	human	52:56	arg1	formation					73:81	initial human dental biofilm formation	44:81	initial human dental biofilm formation	44:81	Effect of mechanically stimulated saliva on initial human dental biofilm formation.
31413280	9	56	from	prominent	1373:1381	arg1	biofilm					1396:1402	the early biofilm	1386:1402	the early biofilm	1386:1402	Cells reacting with antibody against Rothia or Haemophilus were prominent in the early biofilm.
31413280	5	57	theme	activity	705:712	arg1	Lack					689:692	Lack	689:692	Lack of binding activity	689:712	Lack of binding activity was noted with Streptococcus mutans and Lactobacillus casei.
31413280	6	58	theme	Streptococcus	902:914	arg1	anginosus					916:924	Streptococcus anginosus	902:924	Streptococcus anginosus	902:924	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	6	59	theme	Microarray	809:818	arg1	analyses					828:835	Human Oral Microbe Identification Microarray (HOMIM) analyses	775:835	Human Oral Microbe Identification Microarray (HOMIM) analyses	775:835	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	0	60	theme	initial	44:50	arg1	formation					73:81	initial human dental biofilm formation	44:81	initial human dental biofilm formation	44:81	Effect of mechanically stimulated saliva on initial human dental biofilm formation.
31413280	10	61	with	saliva	1551:1556	arg1	stimuli					1583:1589	multiple orosensory stimuli	1563:1589	multiple orosensory stimuli	1563:1589	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	8	62	from	volunteer	1298:1306	arg1	serotype					1271:1278	the type 4 RPS-reactive serotype	1247:1278	the type 4 RPS-reactive serotype	1247:1278	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	8	62	from	volunteer	1298:1306	arg1	absent					1284:1289	absent	1284:1289	absent	1284:1289	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	2	63	theme	unstimulated	228:239	arg1	saliva					256:261	both unstimulated and stimulated saliva	223:261	both unstimulated and stimulated saliva	223:261	Interaction between oral bacteria and both unstimulated and stimulated saliva was examined in vitro by laying labeled bacteria over SDS-PAGE-separated salivary proteins.
31413280	6	64	theme	Identification	794:807	arg1	HOMIM					821:825	HOMIM	821:825	HOMIM	821:825	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	6	64	theme	Identification	794:807	arg1	Microarray					809:818	Human Oral Microbe Identification Microarray	775:818	Human Oral Microbe Identification Microarray (HOMIM) analyses	775:835	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	3	65	theme	retrievable	519:529	arg1	chips					538:542	retrievable enamel chips	519:542	retrievable enamel chips	519:542	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	10	66	theme	stimulating	1539:1549	arg1	saliva					1551:1556	stimulating saliva	1539:1556	stimulating saliva with multiple orosensory stimuli	1539:1589	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	3	67	dep	in	381:382	arg1	vivo					384:387	vivo	384:387	vivo	384:387	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	9	68	theme	early	1390:1394	arg1	biofilm					1396:1402	the early biofilm	1386:1402	the early biofilm	1386:1402	Cells reacting with antibody against Rothia or Haemophilus were prominent in the early biofilm.
31413280	8	69	theme	type	1251:1254	arg1	serotype					1271:1278	the type 4 RPS-reactive serotype	1247:1278	the type 4 RPS-reactive serotype	1247:1278	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	8	69	theme	type	1251:1254	arg1	absent					1284:1289	absent	1284:1289	absent	1284:1289	Differences in bacterial colonization were noted between the two volunteers, while the type 4 RPS-reactive serotype was absent in one volunteer.
31413280	6	70	theme	Microbe	786:792	arg1	HOMIM					821:825	HOMIM	821:825	HOMIM	821:825	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	6	70	theme	Microbe	786:792	arg1	Microarray					809:818	Human Oral Microbe Identification Microarray	775:818	Human Oral Microbe Identification Microarray (HOMIM) analyses	775:835	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	3	71	theme	intraoral	492:500	arg1	stent					502:506	an intraoral stent	489:506	an intraoral stent containing retrievable enamel chips	489:542	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	7	72	theme	polysaccharides	1141:1155	arg1	serotypes					1064:1072	different serotypes	1054:1072	different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS)	1054:1161	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
31413280	3	73	from	effects	359:365	arg1	biofilm					389:395	in vivo biofilm	381:395	in vivo biofilm	381:395	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	3	73	from	effects	359:365	arg1	composition					408:418	microbial composition	398:418	microbial composition	398:418	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	3	73	from	effects	359:365	arg1	arrangement					433:443	spatial arrangement	425:443	spatial arrangement	425:443	The effects of chewing on in vivo biofilm, microbial composition, and spatial arrangement were examined in two human volunteers using an intraoral stent containing retrievable enamel chips.
31413280	6	74	theme	Oral	781:784	arg1	HOMIM					821:825	HOMIM	821:825	HOMIM	821:825	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	6	74	theme	Oral	781:784	arg1	Microarray					809:818	Human Oral Microbe Identification Microarray	775:818	Human Oral Microbe Identification Microarray (HOMIM) analyses	775:835	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	1	75	theme	stimulated	132:141	arg1	saliva					143:148	mechanically stimulated saliva	119:148	mechanically stimulated saliva	119:148	This study evaluated the impact of mechanically stimulated saliva on initial bacterial colonization.
31413280	9	76	from	biofilm	1396:1402	arg1	prominent					1373:1381	prominent	1373:1381	prominent	1373:1381	Cells reacting with antibody against Rothia or Haemophilus were prominent in the early biofilm.
31413280	0	77	theme	biofilm	65:71	arg1	formation					73:81	initial human dental biofilm formation	44:81	initial human dental biofilm formation	44:81	Effect of mechanically stimulated saliva on initial human dental biofilm formation.
31413280	2	78	theme	oral	205:208	arg1	bacteria					210:217	oral bacteria	205:217	oral bacteria	205:217	Interaction between oral bacteria and both unstimulated and stimulated saliva was examined in vitro by laying labeled bacteria over SDS-PAGE-separated salivary proteins.
31413280	6	79	theme	Human	775:779	arg1	HOMIM					821:825	HOMIM	821:825	HOMIM	821:825	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	6	79	theme	Human	775:779	arg1	Microarray					809:818	Human Oral Microbe Identification Microarray	775:818	Human Oral Microbe Identification Microarray (HOMIM) analyses	775:835	Human Oral Microbe Identification Microarray (HOMIM) analyses revealed a consistent chewing-related increase in the binding of Streptococcus anginosus and Streptococcus gordonii.
31413280	1	80	theme	saliva	143:148	arg1	impact					109:114	the impact	105:114	the impact of mechanically stimulated saliva on initial bacterial colonization	105:182	This study evaluated the impact of mechanically stimulated saliva on initial bacterial colonization.
31413280	10	81	from	variations	1471:1480	arg1	patterns					1529:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	both in vitro and in vivo bacterial binding patterns	1485:1536	While analysis of the data obtained demonstrated inter-individual variations in both in vitro and in vivo bacterial binding patterns, stimulating saliva with multiple orosensory stimuli may modulate oral bacterial colonization of tooth surfaces.
31413280	5	82	theme	binding	697:703	arg1	activity					705:712	binding activity	697:712	binding activity	697:712	Lack of binding activity was noted with Streptococcus mutans and Lactobacillus casei.
31413280	0	83	theme	dental	58:63	arg1	formation					73:81	initial human dental biofilm formation	44:81	initial human dental biofilm formation	44:81	Effect of mechanically stimulated saliva on initial human dental biofilm formation.
31413280	7	84	theme	Immunofluorescence	954:971	arg1	microscopy					973:982	Immunofluorescence microscopy	954:982	Immunofluorescence microscopy	954:982	Immunofluorescence microscopy demonstrated the presence of multi-species colonies and cells bearing different serotypes of the coaggregation-mediating streptococcal cell-surface receptor polysaccharides (RPS).
30550822	12	0	theme	IL17	2143:2146	arg1	production					2129:2138	production	2129:2138	production	2129:2138	We found bacteria in tumors to induce production of IL17, which promotes influx of intratumor B cells that promote tumor growth and progression.
30550822	4	1	theme	epithelial	876:885	arg1	Apc					887:889	colon epithelial Apc	870:889	colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl)	870:913	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	7	2	theme	neutrophils	1260:1270	arg1	depletion					1247:1255	depletion	1247:1255	depletion of neutrophils	1247:1270	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	11	3	theme	antibody	1958:1965	arg1	Administration					1910:1923	Administration	1910:1923	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice	1910:2007	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
30550822	3	4	with	littermates	634:644	arg1	deletion					576:583	conditional deletion	564:583	conditional deletion of neutrophils	564:598	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	13	5	theme	mice	2266:2269	arg1	comparisons					2251:2261	comparisons	2251:2261	comparisons of mice with vs without neutrophils	2251:2297	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	1	6	theme	&	115:115	arg1	AIMS					117:120	BACKGROUND & AIMS	104:120	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.	104:341	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	4	7	theme	conditional	846:856	arg1	deletion					858:865	conditional deletion	846:865	conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl)	846:913	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	11	8	theme	neutrophil-deficient	1983:2002	arg1	mice					2004:2007	neutrophil-deficient mice	1983:2007	neutrophil-deficient mice	1983:2007	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
30550822	3	9	theme	Colitis-associated	507:524	arg1	cancer					532:537	Colitis-associated colon cancer	507:537	Colitis-associated colon cancer	507:537	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	12	10	from	bacteria	2100:2107	arg1	tumors					2112:2117	tumors	2112:2117	tumors	2112:2117	We found bacteria in tumors to induce production of IL17, which promotes influx of intratumor B cells that promote tumor growth and progression.
30550822	3	11	theme	dextran	723:729	arg1	sodium					739:744	dextran sulfate sodium	723:744	dextran sulfate sodium	723:744	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	10	12	theme	colon	1854:1858	arg1	tumors					1860:1865	colon tumors	1854:1865	colon tumors from neutrophil-deficient vs control mice	1854:1907	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	10	13	from	differences	1797:1807	arg1	composition					1816:1826	the composition	1812:1826	the composition of the microbiota	1812:1844	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	7	14	with	mice	1189:1192	arg1	tumors					1239:1244	inflammation-induced and sporadic colon tumors	1199:1244	inflammation-induced and sporadic colon tumors	1199:1244	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	3	15	theme	azoxythmethane	701:714	arg1	administration					683:696	administration	683:696	administration of azoxythmethane and/or dextran sulfate sodium	683:744	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	10	16	theme	microbiota	1835:1844	arg1	composition					1816:1826	the composition	1812:1826	the composition of the microbiota	1812:1844	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	13	17	theme	tumor-associated	2403:2418	arg1	responses					2433:2441	tumor-associated inflammatory responses	2403:2441	tumor-associated inflammatory responses	2403:2441	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	9	18	theme	Neutrophil	1543:1552	arg1	depletion					1554:1562	Neutrophil depletion	1543:1562	Neutrophil depletion	1543:1562	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	0	19	from	Invasion	70:77	arg1	Mice					98:101	Mice	98:101	Mice	98:101	Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice.
30550822	12	20	theme	intratumor	2174:2183	arg1	cells					2187:2191	intratumor B cells	2174:2191	intratumor B cells that promote tumor growth and progression	2174:2233	We found bacteria in tumors to induce production of IL17, which promotes influx of intratumor B cells that promote tumor growth and progression.
30550822	3	21	theme	sodium	739:744	arg1	administration					683:696	administration	683:696	administration of azoxythmethane and/or dextran sulfate sodium	683:744	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	3	22	theme	conditional	564:574	arg1	deletion					576:583	conditional deletion	564:583	conditional deletion of neutrophils	564:598	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	5	23	theme	Primary	916:922	arg1	tissues					936:942	Primary colon tumor tissues	916:942	Primary colon tumor tissues from these mice	916:958	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	8	24	theme	control	1529:1535	arg1	mice					1537:1540	control mice	1529:1540	control mice	1529:1540	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	12	25	theme	cells	2187:2191	arg1	influx					2164:2169	influx	2164:2169	influx of intratumor B cells that promote tumor growth and progression	2164:2233	We found bacteria in tumors to induce production of IL17, which promotes influx of intratumor B cells that promote tumor growth and progression.
30550822	5	26	theme	fluorescence	1048:1059	arg1	hybridization					1069:1081	fluorescence in situ hybridization	1048:1081	fluorescence in situ hybridization analyses	1048:1090	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	9	27	theme	increased	1580:1588	arg1	numbers					1590:1596	increased numbers	1580:1596	increased numbers of bacteria in tumors and proliferation of tumor cells	1580:1651	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	8	28	theme	RNA	1341:1343	arg1	analysis					1356:1363	RNA sequencing analysis	1341:1363	RNA sequencing analysis	1341:1363	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	3	29	with	mice	554:557	arg1	deletion					576:583	conditional deletion	564:583	conditional deletion of neutrophils	564:598	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	1	30	with	patients	315:322	arg1	cancer					335:340	colon cancer	329:340	colon cancer	329:340	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	7	31	dep	RESULTS	1178:1184	arg1	mice					1189:1192	mice	1189:1192	mice with inflammation-induced and sporadic colon tumors	1189:1244	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	0	32	theme	Colon	82:86	arg1	Tumors					88:93	Colon Tumors	82:93	Colon Tumors	82:93	Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice.
30550822	1	33	theme	patients	315:322	arg1	outcomes					303:310	outcomes	303:310	outcomes of patients with colon cancer	303:340	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	1	34	theme	prevalent	153:161	arg1	cells					170:174	the most prevalent immune cells	144:174	the most prevalent immune cells	144:174	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	9	35	theme	tumor-cell	1654:1663	arg1	damage					1669:1674	tumor-cell DNA damage	1654:1674	tumor-cell DNA damage	1654:1674	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	7	36	theme	colon	1233:1237	arg1	tumors					1239:1244	inflammation-induced and sporadic colon tumors	1199:1244	inflammation-induced and sporadic colon tumors	1199:1244	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	1	37	theme	colon	329:333	arg1	cancer					335:340	colon cancer	329:340	colon cancer	329:340	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	9	38	from	response	1697:1704	arg1	proliferation					1624:1636	proliferation	1624:1636	proliferation of tumor cells	1624:1651	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	9	38	from	response	1697:1704	arg1	tumors					1613:1618	tumors	1613:1618	tumors	1613:1618	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	5	39	theme	tumor	930:934	arg1	tissues					936:942	Primary colon tumor tissues	916:942	Primary colon tumor tissues from these mice	916:958	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	2	40	theme	colon	478:482	arg1	tumorigenesis					484:496	colon tumorigenesis	478:496	colon tumorigenesis	478:496	Trials of inhibitors of neutrophil trafficking are underway in patients with cancer, but it is not clear how neutrophils contribute to colon tumorigenesis.
30550822	0	41	from	Growth	59:64	arg1	Mice					98:101	Mice	98:101	Mice	98:101	Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice.
30550822	4	42	theme	colon	756:760	arg1	tumorigenesis					762:774	Sporadic colon tumorigenesis	747:774	Sporadic colon tumorigenesis	747:774	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	2	43	theme	neutrophil	367:376	arg1	trafficking					378:388	neutrophil trafficking	367:388	neutrophil trafficking	367:388	Trials of inhibitors of neutrophil trafficking are underway in patients with cancer, but it is not clear how neutrophils contribute to colon tumorigenesis.
30550822	2	44	theme	inhibitors	353:362	arg1	Trials					343:348	Trials	343:348	Trials of inhibitors of neutrophil trafficking	343:388	Trials of inhibitors of neutrophil trafficking are underway in patients with cancer, but it is not clear how neutrophils contribute to colon tumorigenesis.
30550822	1	45	theme	colon	256:260	arg1	tumors					262:267	colon tumors	256:267	colon tumors	256:267	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	9	46	theme	cells	1647:1651	arg1	proliferation					1624:1636	proliferation	1624:1636	proliferation of tumor cells	1624:1651	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	9	46	theme	cells	1647:1651	arg1	tumors					1613:1618	tumors	1613:1618	tumors	1613:1618	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	5	47	theme	quantitative	1004:1015	arg1	reaction					1034:1041	quantitative polymerase chain reaction	1004:1041	quantitative polymerase chain reaction	1004:1041	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	11	48	theme	less-invasive	2036:2048	arg1	tumors					2050:2055	less-invasive tumors	2036:2055	less-invasive tumors	2036:2055	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
30550822	0	49	theme	Tumor-Associated	21:36	arg1	Microbiota					38:47	Tumor-Associated Microbiota	21:47	Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice	21:101	Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice.
30550822	13	50	theme	colon	2329:2333	arg1	growth					2341:2346	slow colon tumor growth	2324:2346	slow colon tumor growth	2324:2346	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	1	51	theme	BACKGROUND	104:113	arg1	AIMS					117:120	BACKGROUND & AIMS	104:120	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.	104:341	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	3	52	dep	mice	554:557	arg1	LysMCre					601:607	LysMCre	601:607	LysMCre	601:607	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	7	53	theme	tumors	1333:1338	arg1	proliferation					1294:1306	proliferation	1294:1306	proliferation	1294:1306	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	7	53	theme	tumors	1333:1338	arg1	invasiveness					1313:1324	invasiveness	1313:1324	invasiveness	1313:1324	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	7	53	theme	tumors	1333:1338	arg1	growth					1286:1291	growth	1286:1291	growth	1286:1291	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	13	54	theme	inflammatory	2420:2431	arg1	responses					2433:2441	tumor-associated inflammatory responses	2403:2441	tumor-associated inflammatory responses	2403:2441	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	3	55	theme	wild-type	624:632	arg1	LysMCre					647:653	LysMCre	647:653	LysMCre	647:653	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	3	55	theme	wild-type	624:632	arg1	littermates					634:644	wild-type littermates	624:644	wild-type littermates (LysMCre;Mcl1wt/wt, control mice)	624:678	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	4	56	dep	Apc	887:889	arg1	Cdx2-CreERT2					892:903	Cdx2-CreERT2	892:903	Cdx2-CreERT2;Apcfl/fl	892:912	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	5	57	theme	polymerase	1017:1026	arg1	reaction					1034:1041	quantitative polymerase chain reaction	1004:1041	quantitative polymerase chain reaction	1004:1041	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	8	58	theme	colon	1484:1488	arg1	tumors					1490:1495	neutrophil-deficient colon tumors	1463:1495	neutrophil-deficient colon tumors	1463:1495	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	10	59	theme	ribosomal	1749:1757	arg1	sequencing					1763:1772	The 16s ribosomal RNA sequencing	1741:1772	The 16s ribosomal RNA sequencing	1741:1772	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	5	60	from	mice	955:958	arg1	tissues					936:942	Primary colon tumor tissues	916:942	Primary colon tumor tissues from these mice	916:958	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	5	61	theme	RNA	988:990	arg1	sequencing					992:1001	RNA sequencing	988:1001	RNA sequencing	988:1001	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	13	62	dep	CONCLUSIONS	2236:2246	arg1	comparisons					2251:2261	comparisons	2251:2261	comparisons of mice with vs without neutrophils	2251:2297	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	6	63	theme	tumor-associated	1103:1118	arg1	microbiota					1120:1129	tumor-associated microbiota	1103:1129	tumor-associated microbiota	1103:1129	Fecal and tumor-associated microbiota were assessed by 16s ribosomal RNA sequencing.
30550822	10	64	theme	significant	1785:1795	arg1	differences					1797:1807	significant differences	1785:1807	significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice	1785:1907	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	4	65	theme	colon	870:874	arg1	Apc					887:889	colon epithelial Apc	870:889	colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl)	870:913	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	5	66	dep	in	1061:1062	arg1	situ					1064:1067	situ	1064:1067	situ	1064:1067	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	11	67	dep	resulted	2009:2016	arg1	compared					2057:2064	compared	2057:2064	compared with mice given vehicle	2057:2088	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
30550822	3	68	theme	colon	526:530	arg1	cancer					532:537	Colitis-associated colon cancer	507:537	Colitis-associated colon cancer	507:537	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	3	69	dep	LysMCre	647:653	arg1	Mcl1wt/wt					655:663	Mcl1wt/wt	655:663	Mcl1wt/wt	655:663	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	3	69	dep	LysMCre	647:653	arg1	mice					674:677	control mice	666:677	control mice	666:677	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	4	70	theme	Apc	887:889	arg1	deletion					858:865	conditional deletion	846:865	conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl)	846:913	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	9	71	from	numbers	1590:1596	arg1	proliferation					1624:1636	proliferation	1624:1636	proliferation of tumor cells	1624:1651	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	9	71	from	numbers	1590:1596	arg1	tumors					1613:1618	tumors	1613:1618	tumors	1613:1618	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	13	72	theme	slow	2324:2327	arg1	growth					2341:2346	slow colon tumor growth	2324:2346	slow colon tumor growth	2324:2346	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	1	73	theme	immune	163:168	arg1	cells					170:174	the most prevalent immune cells	144:174	the most prevalent immune cells	144:174	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	4	74	dep	Cdx2-CreERT2	892:903	arg1	Apcfl/fl					905:912	Apcfl/fl	905:912	Apcfl/fl	905:912	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	3	75	theme	sulfate	731:737	arg1	sodium					739:744	dextran sulfate sodium	723:744	dextran sulfate sodium	723:744	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	8	76	theme	colon	1511:1515	arg1	tumors					1517:1522	colon tumors	1511:1522	colon tumors from control mice	1511:1540	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	6	77	theme	ribosomal	1152:1160	arg1	sequencing					1166:1175	ribosomal RNA sequencing	1152:1175	ribosomal RNA sequencing	1152:1175	Fecal and tumor-associated microbiota were assessed by 16s ribosomal RNA sequencing.
30550822	11	78	theme	neutralizing	1945:1956	arg1	antibody					1958:1965	a neutralizing antibody	1943:1965	a neutralizing antibody against IL17 to neutrophil-deficient mice	1943:2007	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
30550822	5	79	theme	hybridization	1069:1081	arg1	analyses					1083:1090	fluorescence in situ hybridization analyses	1048:1090	fluorescence in situ hybridization analyses	1048:1090	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	10	80	theme	control	1896:1902	arg1	mice					1904:1907	neutrophil-deficient vs control mice	1872:1907	neutrophil-deficient vs control mice	1872:1907	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	1	81	theme	colon	203:207	arg1	tumors					209:214	colon tumors	203:214	colon tumors	203:214	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	12	82	theme	tumor	2206:2210	arg1	growth					2212:2217	tumor growth	2206:2217	tumor growth	2206:2217	We found bacteria in tumors to induce production of IL17, which promotes influx of intratumor B cells that promote tumor growth and progression.
30550822	10	83	theme	neutrophil-deficient	1872:1891	arg1	mice					1904:1907	neutrophil-deficient vs control mice	1872:1907	neutrophil-deficient vs control mice	1872:1907	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	2	84	with	patients	406:413	arg1	cancer					420:425	cancer	420:425	cancer	420:425	Trials of inhibitors of neutrophil trafficking are underway in patients with cancer, but it is not clear how neutrophils contribute to colon tumorigenesis.
30550822	3	85	dep	METHODS	499:505	arg1	induced					543:549	induced	543:549	was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium	539:744	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	13	86	theme	responses	2433:2441	arg1	numbers					2379:2385	numbers	2379:2385	numbers of bacteria and tumor-associated inflammatory responses	2379:2441	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	5	87	theme	colon	924:928	arg1	tissues					936:942	Primary colon tumor tissues	916:942	Primary colon tumor tissues from these mice	916:958	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	6	88	theme	RNA	1162:1164	arg1	sequencing					1166:1175	ribosomal RNA sequencing	1152:1175	ribosomal RNA sequencing	1152:1175	Fecal and tumor-associated microbiota were assessed by 16s ribosomal RNA sequencing.
30550822	12	89	theme	B	2185:2185	arg1	cells					2187:2191	intratumor B cells	2174:2191	intratumor B cells that promote tumor growth and progression	2174:2233	We found bacteria in tumors to induce production of IL17, which promotes influx of intratumor B cells that promote tumor growth and progression.
30550822	11	90	theme	antibiotics	1928:1938	arg1	Administration					1910:1923	Administration	1910:1923	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice	1910:2007	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
30550822	5	91	theme	in	1061:1062	arg1	hybridization					1069:1081	fluorescence in situ hybridization	1048:1081	fluorescence in situ hybridization analyses	1048:1090	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	3	92	theme	neutrophils	588:598	arg1	deletion					576:583	conditional deletion	564:583	conditional deletion of neutrophils	564:598	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	0	93	theme	Tumors	88:93	arg1	Invasion					70:77	Invasion	70:77	Invasion	70:77	Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice.
30550822	0	93	theme	Tumors	88:93	arg1	Growth					59:64	Growth	59:64	Growth	59:64	Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice.
30550822	1	94	from	cells	170:174	arg1	microenvironment					183:198	the microenvironment	179:198	the microenvironment of colon tumors	179:214	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	9	95	theme	bacteria	1601:1608	arg1	response					1697:1704	an inflammatory response	1681:1704	an inflammatory response mediated by interleukin 17 (IL17)	1681:1738	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	9	95	theme	bacteria	1601:1608	arg1	damage					1669:1674	tumor-cell DNA damage	1654:1674	tumor-cell DNA damage	1654:1674	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	9	95	theme	bacteria	1601:1608	arg1	numbers					1590:1596	increased numbers	1580:1596	increased numbers of bacteria in tumors and proliferation of tumor cells	1580:1651	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	8	96	theme	sequencing	1345:1354	arg1	analysis					1356:1363	RNA sequencing analysis	1341:1363	RNA sequencing analysis	1341:1363	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	7	97	theme	sporadic	1224:1231	arg1	tumors					1239:1244	inflammation-induced and sporadic colon tumors	1199:1244	inflammation-induced and sporadic colon tumors	1199:1244	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	9	98	theme	inflammatory	1684:1695	arg1	response					1697:1704	an inflammatory response	1681:1704	an inflammatory response mediated by interleukin 17 (IL17)	1681:1738	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	8	99	from	mice	1537:1540	arg1	tumors					1517:1522	colon tumors	1511:1522	colon tumors from control mice	1511:1540	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	4	100	theme	Sporadic	747:754	arg1	tumorigenesis					762:774	Sporadic colon tumorigenesis	747:774	Sporadic colon tumorigenesis	747:774	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	7	101	theme	inflammation-induced	1199:1218	arg1	tumors					1239:1244	inflammation-induced and sporadic colon tumors	1199:1244	inflammation-induced and sporadic colon tumors	1199:1244	RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors.
30550822	9	102	theme	tumor	1641:1645	arg1	cells					1647:1651	tumor cells	1641:1651	tumor cells	1641:1651	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	8	103	theme	antimicrobial	1396:1408	arg1	processes					1427:1435	antimicrobial and inflammatory processes	1396:1435	antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice	1396:1540	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	1	104	theme	tumors	262:267	arg1	growth					246:251	growth	246:251	growth of colon tumors	246:267	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	10	105	from	mice	1904:1907	arg1	tumors					1860:1865	colon tumors	1854:1865	colon tumors from neutrophil-deficient vs control mice	1854:1907	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	8	106	theme	inflammatory	1414:1425	arg1	processes					1427:1435	antimicrobial and inflammatory processes	1396:1435	antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice	1396:1540	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	11	107	theme	tumors	2050:2055	arg1	development					2021:2031	development	2021:2031	development of less-invasive tumors	2021:2055	Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle.
30550822	13	108	theme	tumor	2335:2339	arg1	growth					2341:2346	slow colon tumor growth	2324:2346	slow colon tumor growth	2324:2346	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	3	109	dep	LysMCre	601:607	arg1	Mcl1fl/fl					609:617	Mcl1fl/fl	609:617	Mcl1fl/fl	609:617	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550822	9	110	theme	DNA	1665:1667	arg1	damage					1669:1674	tumor-cell DNA damage	1654:1674	tumor-cell DNA damage	1654:1674	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	9	111	from	damage	1669:1674	arg1	proliferation					1624:1636	proliferation	1624:1636	proliferation of tumor cells	1624:1651	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	9	111	from	damage	1669:1674	arg1	tumors					1613:1618	tumors	1613:1618	tumors	1613:1618	Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17).
30550822	4	112	theme	neutrophil-deficient	792:811	arg1	mice					836:839	neutrophil-deficient and neutrophil-replete mice	792:839	neutrophil-deficient and neutrophil-replete mice	792:839	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	2	113	theme	trafficking	378:388	arg1	inhibitors					353:362	inhibitors	353:362	inhibitors of neutrophil trafficking	353:388	Trials of inhibitors of neutrophil trafficking are underway in patients with cancer, but it is not clear how neutrophils contribute to colon tumorigenesis.
30550822	5	114	theme	chain	1028:1032	arg1	reaction					1034:1041	quantitative polymerase chain reaction	1004:1041	quantitative polymerase chain reaction	1004:1041	Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses.
30550822	13	115	theme	bacteria	2390:2397	arg1	numbers					2379:2385	numbers	2379:2385	numbers of bacteria and tumor-associated inflammatory responses	2379:2441	CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
30550822	4	116	theme	neutrophil-replete	817:834	arg1	mice					836:839	neutrophil-deficient and neutrophil-replete mice	792:839	neutrophil-deficient and neutrophil-replete mice	792:839	Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl).
30550822	10	117	theme	RNA	1759:1761	arg1	sequencing					1763:1772	The 16s ribosomal RNA sequencing	1741:1772	The 16s ribosomal RNA sequencing	1741:1772	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	1	118	dep	AIMS	117:120	arg1	believed					226:233	believed	226:233	are believed to promote growth of colon tumors	222:267	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	1	118	dep	AIMS	117:120	arg1	correlate					288:296	correlate	288:296	correlate with outcomes of patients with colon cancer	288:340	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	1	118	dep	AIMS	117:120	arg1	cells					170:174	the most prevalent immune cells	144:174	the most prevalent immune cells	144:174	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	8	119	theme	neutrophil-deficient	1463:1482	arg1	tumors					1490:1495	neutrophil-deficient colon tumors	1463:1495	neutrophil-deficient colon tumors	1463:1495	RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice.
30550822	10	120	theme	16s	1745:1747	arg1	sequencing					1763:1772	The 16s ribosomal RNA sequencing	1741:1772	The 16s ribosomal RNA sequencing	1741:1772	The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice.
30550822	1	121	theme	tumors	209:214	arg1	microenvironment					183:198	the microenvironment	179:198	the microenvironment of colon tumors	179:214	BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer.
30550822	3	122	theme	control	666:672	arg1	mice					674:677	control mice	666:677	control mice	666:677	METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium.
30550553	4	0	theme	long	867:870	arg1	C18					872:874	long C18	867:874	long C18	867:874	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	8	1	theme	bound	1423:1427	arg1	GlcCer					1429:1434	a bound GlcCer	1421:1434	a bound GlcCer	1421:1434	Here we found that if GLTP has a bound GlcCer the association with VAP-A is weaker.
30550553	8	2	contain	has	1417:1419	arg1	GLTP					1412:1415	GLTP	1412:1415	GLTP	1412:1415	Here we found that if GLTP has a bound GlcCer the association with VAP-A is weaker.
30550553	8	2	contain	has	1417:1419	arg2	GlcCer					1429:1434	a bound GlcCer	1421:1434	a bound GlcCer	1421:1434	Here we found that if GLTP has a bound GlcCer the association with VAP-A is weaker.
30550553	3	3	theme	N-linked	622:629	arg1	species					642:648	different N-linked acyl chain species	612:648	different N-linked acyl chain species of glucosylceramide	612:668	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	6	4	dep	occurs	1282:1287	arg1	addressed					1302:1310	addressed	1302:1310	occurs has not been addressed before	1282:1317	It has long been postulated that GLTP would be a sensor in the sphingolipid synthesis machinery, but how this mechanistically occurs has not been addressed before.
30550553	2	5	dep	protein	393:399	arg1	A					401:401	A	401:401	vesicle-associated membrane protein-associated protein A (VAP-A)	346:409	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	1	6	theme	acidic	206:211	arg1	tract					213:217	an acidic tract	203:217	an acidic tract	203:217	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	2	7	theme	wide	435:438	arg1	range					440:444	a wide range	433:444	a wide range of ER functions	433:460	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	4	8	theme	plasmon	687:693	arg1	resonance					695:703	surface plasmon resonance	679:703	surface plasmon resonance	679:703	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	4	9	link	N-linked	778:785	arg1	glucosylceramides					814:830	N-linked fully saturated acyl chain glucosylceramides	778:830	N-linked fully saturated acyl chain glucosylceramides	778:830	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	1	10	located	found	127:131	arg2	protein					105:111	The glycolipid transfer protein	81:111	The glycolipid transfer protein	81:111	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	1	10	located	found	127:131	arg1	cytoplasm					140:148	the cytoplasm	136:148	the cytoplasm	136:148	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	1	10	located	found	127:131	arg2	GLTP					114:117	GLTP	114:117	GLTP	114:117	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	4	11	theme	N-linked	778:785	arg1	glucosylceramides					814:830	N-linked fully saturated acyl chain glucosylceramides	778:830	N-linked fully saturated acyl chain glucosylceramides	778:830	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	9	12	theme	several	1559:1565	arg1	VAP-interactors					1577:1591	several potential VAP-interactors	1559:1591	several potential VAP-interactors	1559:1591	We have also used a formula for identifying putative FFAT-domains, and we identified several potential VAP-interactors within the ceramide and sphingolipid synthesis pathways that could be candidates for regulation by GLTP.
30550553	7	13	theme	VAP	1357:1359	arg1	association					1361:1371	the GLTP VAP association	1348:1371	the GLTP VAP association	1348:1371	It is unclear what proteins the GLTP VAP association would influence.
30550553	6	14	theme	synthesis	1232:1240	arg1	machinery					1242:1250	the sphingolipid synthesis machinery	1215:1250	the sphingolipid synthesis machinery	1215:1250	It has long been postulated that GLTP would be a sensor in the sphingolipid synthesis machinery, but how this mechanistically occurs has not been addressed before.
30550553	3	15	theme	acyl	631:634	arg1	species					642:648	different N-linked acyl chain species	612:648	different N-linked acyl chain species of glucosylceramide	612:668	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	9	16	theme	putative	1518:1525	arg1	FFAT-domains					1527:1538	putative FFAT-domains	1518:1538	putative FFAT-domains	1518:1538	We have also used a formula for identifying putative FFAT-domains, and we identified several potential VAP-interactors within the ceramide and sphingolipid synthesis pathways that could be candidates for regulation by GLTP.
30550553	4	17	theme	surface	679:685	arg1	resonance					695:703	surface plasmon resonance	679:703	surface plasmon resonance	679:703	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	6	18	theme	sphingolipid	1219:1230	arg1	machinery					1242:1250	the sphingolipid synthesis machinery	1215:1250	the sphingolipid synthesis machinery	1215:1250	It has long been postulated that GLTP would be a sensor in the sphingolipid synthesis machinery, but how this mechanistically occurs has not been addressed before.
30550553	0	19	theme	Glucosylceramide	0:15	arg1	length					28:33	Glucosylceramide acyl chain length	0:33	Glucosylceramide acyl chain length	0:33	Glucosylceramide acyl chain length is sensed by the glycolipid transfer protein.
30550553	3	20	link	N-linked	622:629	arg1	species					642:648	different N-linked acyl chain species	612:648	different N-linked acyl chain species of glucosylceramide	612:668	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	5	21	theme	fluorescence	1036:1047	arg1	blueshifts					1049:1058	the intrinsic GLTP tryptophan fluorescence blueshifts	1006:1058	the intrinsic GLTP tryptophan fluorescence blueshifts	1006:1058	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
30550553	0	22	theme	acyl	17:20	arg1	length					28:33	Glucosylceramide acyl chain length	0:33	Glucosylceramide acyl chain length	0:33	Glucosylceramide acyl chain length is sensed by the glycolipid transfer protein.
30550553	3	23	theme	different	612:620	arg1	species					642:648	different N-linked acyl chain species	612:648	different N-linked acyl chain species of glucosylceramide	612:668	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	8	24	with	association	1440:1450	arg1	VAP-A					1457:1461	VAP-A	1457:1461	VAP-A	1457:1461	Here we found that if GLTP has a bound GlcCer the association with VAP-A is weaker.
30550553	2	25	theme	membrane	365:372	arg1	protein					337:343	a transmembrane ER protein	318:343	a transmembrane ER protein	318:343	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	25	theme	membrane	365:372	arg1	protein					393:399	vesicle-associated membrane protein-associated protein	346:399	vesicle-associated membrane protein-associated protein A (VAP-A)	346:409	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	25	theme	membrane	365:372	arg1	VAP-A					404:408	VAP-A	404:408	VAP-A	404:408	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	6	26	from	sensor	1205:1210	arg1	machinery					1242:1250	the sphingolipid synthesis machinery	1215:1250	the sphingolipid synthesis machinery	1215:1250	It has long been postulated that GLTP would be a sensor in the sphingolipid synthesis machinery, but how this mechanistically occurs has not been addressed before.
30550553	1	27	theme	glycolipid	85:94	arg1	GLTP					114:117	GLTP	114:117	GLTP	114:117	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	1	27	theme	glycolipid	85:94	arg1	protein					105:111	The glycolipid transfer protein	81:111	The glycolipid transfer protein	81:111	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	4	28	theme	shorter	973:979	arg1	counterparts					981:992	their shorter counterparts	967:992	their shorter counterparts	967:992	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	3	29	theme	VAP	553:555	arg1	proteins					557:564	the VAP proteins	549:564	the VAP proteins	549:564	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	2	30	theme	vesicle-associated	346:363	arg1	protein					337:343	a transmembrane ER protein	318:343	a transmembrane ER protein	318:343	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	30	theme	vesicle-associated	346:363	arg1	protein					393:399	vesicle-associated membrane protein-associated protein	346:399	vesicle-associated membrane protein-associated protein A (VAP-A)	346:409	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	30	theme	vesicle-associated	346:363	arg1	VAP-A					404:408	VAP-A	404:408	VAP-A	404:408	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	3	31	theme	glucosylceramide	653:668	arg1	species					642:648	different N-linked acyl chain species	612:648	different N-linked acyl chain species of glucosylceramide	612:668	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	2	32	theme	functions	452:460	arg1	range					440:444	a wide range	433:444	a wide range of ER functions	433:460	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	1	33	theme	transfer	96:103	arg1	GLTP					114:117	GLTP	114:117	GLTP	114:117	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	1	33	theme	transfer	96:103	arg1	protein					105:111	The glycolipid transfer protein	81:111	The glycolipid transfer protein	81:111	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	0	34	theme	chain	22:26	arg1	length					28:33	Glucosylceramide acyl chain length	0:33	Glucosylceramide acyl chain length	0:33	Glucosylceramide acyl chain length is sensed by the glycolipid transfer protein.
30550553	3	35	theme	chain	636:640	arg1	species					642:648	different N-linked acyl chain species	612:648	different N-linked acyl chain species of glucosylceramide	612:668	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	2	36	theme	ER	449:450	arg1	functions					452:460	ER functions	449:460	ER functions	449:460	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	37	theme	ER	334:335	arg1	protein					393:399	vesicle-associated membrane protein-associated protein	346:399	vesicle-associated membrane protein-associated protein A (VAP-A)	346:409	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	37	theme	ER	334:335	arg1	protein					337:343	a transmembrane ER protein	318:343	a transmembrane ER protein	318:343	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	5	38	from	break-point	1077:1087	arg1	ability					1147:1153	the GLTP sensing ability	1130:1153	the GLTP sensing ability	1130:1153	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
30550553	1	39	theme	FFAT-like	164:172	arg1	motif					174:178	a FFAT-like motif	162:178	a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER)	162:268	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	4	40	theme	transfer	717:724	arg1	assay					738:742	a lipid transfer competition assay	709:742	a lipid transfer competition assay	709:742	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	2	41	theme	transmembrane	320:332	arg1	protein					393:399	vesicle-associated membrane protein-associated protein	346:399	vesicle-associated membrane protein-associated protein A (VAP-A)	346:409	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	41	theme	transmembrane	320:332	arg1	protein					337:343	a transmembrane ER protein	318:343	a transmembrane ER protein	318:343	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	5	42	theme	GLTP	1020:1023	arg1	fluorescence					1036:1047	intrinsic GLTP tryptophan fluorescence	1010:1047	the intrinsic GLTP tryptophan fluorescence blueshifts	1006:1058	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
30550553	9	43	theme	potential	1567:1575	arg1	VAP-interactors					1577:1591	several potential VAP-interactors	1559:1591	several potential VAP-interactors	1559:1591	We have also used a formula for identifying putative FFAT-domains, and we identified several potential VAP-interactors within the ceramide and sphingolipid synthesis pathways that could be candidates for regulation by GLTP.
30550553	4	44	theme	lipid	711:715	arg1	assay					738:742	a lipid transfer competition assay	709:742	a lipid transfer competition assay	709:742	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	9	45	used	used	1487:1490	arg2	We					1474:1475	We	1474:1475	We	1474:1475	We have also used a formula for identifying putative FFAT-domains, and we identified several potential VAP-interactors within the ceramide and sphingolipid synthesis pathways that could be candidates for regulation by GLTP.
30550553	4	46	dep	shorter	770:776	arg1	glucosylceramides					814:830	N-linked fully saturated acyl chain glucosylceramides	778:830	N-linked fully saturated acyl chain glucosylceramides	778:830	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	1	47	theme	endoplasmic	243:253	arg1	ER					266:267	ER	266:267	ER	266:267	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	1	47	theme	endoplasmic	243:253	arg1	reticulum					255:263	the endoplasmic reticulum	239:263	the endoplasmic reticulum (ER)	239:268	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	1	48	from	phenylalanines	185:198	arg1	tract					213:217	an acidic tract	203:217	an acidic tract	203:217	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	9	49	theme	sphingolipid	1617:1628	arg1	pathways					1640:1647	the ceramide and sphingolipid synthesis pathways	1600:1647	pathways	1640:1647	We have also used a formula for identifying putative FFAT-domains, and we identified several potential VAP-interactors within the ceramide and sphingolipid synthesis pathways that could be candidates for regulation by GLTP.
30550553	5	50	theme	intrinsic	1010:1018	arg1	fluorescence					1036:1047	intrinsic GLTP tryptophan fluorescence	1010:1047	the intrinsic GLTP tryptophan fluorescence blueshifts	1006:1058	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
30550553	4	51	theme	acyl	803:806	arg1	glucosylceramides					814:830	N-linked fully saturated acyl chain glucosylceramides	778:830	N-linked fully saturated acyl chain glucosylceramides	778:830	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	4	52	theme	saturated	793:801	arg1	glucosylceramides					814:830	N-linked fully saturated acyl chain glucosylceramides	778:830	N-linked fully saturated acyl chain glucosylceramides	778:830	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	4	53	theme	competition	726:736	arg1	assay					738:742	a lipid transfer competition assay	709:742	a lipid transfer competition assay	709:742	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	4	54	used	used	674:677	arg2	We					671:672	We	671:672	We	671:672	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	7	55	theme	GLTP	1352:1355	arg1	association					1361:1371	the GLTP VAP association	1348:1371	the GLTP VAP association	1348:1371	It is unclear what proteins the GLTP VAP association would influence.
30550553	5	56	theme	tryptophan	1025:1034	arg1	fluorescence					1036:1047	intrinsic GLTP tryptophan fluorescence	1010:1047	the intrinsic GLTP tryptophan fluorescence blueshifts	1006:1058	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
30550553	9	57	theme	synthesis	1630:1638	arg1	pathways					1640:1647	the ceramide and sphingolipid synthesis pathways	1600:1647	pathways	1640:1647	We have also used a formula for identifying putative FFAT-domains, and we identified several potential VAP-interactors within the ceramide and sphingolipid synthesis pathways that could be candidates for regulation by GLTP.
30550553	4	58	theme	chain	808:812	arg1	glucosylceramides					814:830	N-linked fully saturated acyl chain glucosylceramides	778:830	N-linked fully saturated acyl chain glucosylceramides	778:830	We used surface plasmon resonance and a lipid transfer competition assay to show that GLTP prefers shorter N-linked fully saturated acyl chain glucosylceramides, such as C8, C12, and C16, whereas long C18, C20, and C24-glucosylceramides are all bound more weakly and transported more slowly than their shorter counterparts.
30550553	1	59	dep	motif	174:178	arg1	phenylalanines					185:198	two phenylalanines	181:198	two phenylalanines in an acidic tract	181:217	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	5	60	from	Changes	995:1001	arg1	blueshifts					1049:1058	the intrinsic GLTP tryptophan fluorescence blueshifts	1006:1058	the intrinsic GLTP tryptophan fluorescence blueshifts	1006:1058	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
30550553	0	61	theme	transfer	63:70	arg1	protein					72:78	the glycolipid transfer protein	48:78	the glycolipid transfer protein	48:78	Glucosylceramide acyl chain length is sensed by the glycolipid transfer protein.
30550553	1	62	contain	has	158:160	arg2	motif					174:178	a FFAT-like motif	162:178	a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER)	162:268	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	1	62	contain	has	158:160	arg1	it					155:156	it	155:156	it	155:156	The glycolipid transfer protein, GLTP, can be found in the cytoplasm, and it has a FFAT-like motif (two phenylalanines in an acidic tract) that targets it to the endoplasmic reticulum (ER).
30550553	0	63	theme	glycolipid	52:61	arg1	protein					72:78	the glycolipid transfer protein	48:78	the glycolipid transfer protein	48:78	Glucosylceramide acyl chain length is sensed by the glycolipid transfer protein.
30550553	3	64	theme	GLTP	594:597	arg1	capacity					582:589	the capacity	578:589	the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide	578:668	We have addressed the mechanisms that might regulate the association between GLTP and the VAP proteins by studying the capacity of GLTP to recognize different N-linked acyl chain species of glucosylceramide.
30550553	2	65	theme	protein-associated	374:391	arg1	protein					337:343	a transmembrane ER protein	318:343	a transmembrane ER protein	318:343	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	65	theme	protein-associated	374:391	arg1	protein					393:399	vesicle-associated membrane protein-associated protein	346:399	vesicle-associated membrane protein-associated protein A (VAP-A)	346:409	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	2	65	theme	protein-associated	374:391	arg1	VAP-A					404:408	VAP-A	404:408	VAP-A	404:408	We have previously shown that GLTP can bind to a transmembrane ER protein, vesicle-associated membrane protein-associated protein A (VAP-A), which is involved in a wide range of ER functions.
30550553	5	66	theme	sensing	1139:1145	arg1	ability					1147:1153	the GLTP sensing ability	1130:1153	the GLTP sensing ability	1130:1153	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
30550553	5	67	theme	GLTP	1134:1137	arg1	ability					1147:1153	the GLTP sensing ability	1130:1153	the GLTP sensing ability	1130:1153	Changes in the intrinsic GLTP tryptophan fluorescence blueshifts, also indicate a break-point between C16- and C18-glucosylceramide in the GLTP sensing ability.
29513215	1	0	theme	O-linked	58:65	arg1	glycosylation					67:79	O-linked glycosylation	58:79	O-linked glycosylation	58:79	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	0	1	theme	sweet	4:8	arg1	side					10:13	The sweet side	0:13	The sweet side of vimentin	0:25	The sweet side of vimentin.
29513215	0	2	theme	vimentin	18:25	arg1	side					10:13	The sweet side	0:13	The sweet side of vimentin	0:25	The sweet side of vimentin.
29513215	1	3	link	O-linked	58:65	arg1	glycosylation					67:79	O-linked glycosylation	58:79	O-linked glycosylation	58:79	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	1	4	theme	normal	141:146	arg1	conditions					148:157	normal conditions	141:157	normal conditions	141:157	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	1	5	theme	Chlamydia	179:187	arg1	bacteria					189:196	Chlamydia bacteria	179:196	Chlamydia bacteria	179:196	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	1	6	dep	they	217:220	arg1	infect					222:227	infect	222:227	infect cells	222:233	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	1	7	theme	bacteria	189:196	arg1	ability					168:174	the ability	164:174	the ability of Chlamydia bacteria to replicate after they infect cells	164:233	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	1	7	theme	bacteria	189:196	arg1	interactions					95:106	the interactions	91:106	the interactions between vimentin molecules under normal conditions	91:157	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	1	8	theme	vimentin	116:123	arg1	molecules					125:133	vimentin molecules	116:133	vimentin molecules under normal conditions	116:157	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
29513215	1	9	theme	protein	30:36	arg1	modification					38:49	A protein modification	28:49	A protein modification called O-linked glycosylation	28:79	A protein modification called O-linked glycosylation regulates the interactions between vimentin molecules under normal conditions, and the ability of Chlamydia bacteria to replicate after they infect cells.
31926585	7	0	theme	mechanisms	1188:1197	arg1	elucidation					1169:1179	the elucidation	1165:1179	the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation	1165:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	1	1	theme	annua	175:179	arg1	L.					181:182	the herb medicine Artemisia annua L.	147:182	the herb medicine Artemisia annua L.	147:182	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	6	2	theme	blot	967:970	arg1	analysis					972:979	Further lectin immunofluorescence and lectin blot analysis	922:979	analysis	972:979	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	3	3	theme	present	336:342	arg1	study					344:348	the present study	332:348	the present study	332:348	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	6	4	link	N-linked	1053:1060	arg1	carbohydrate					1062:1073	N-linked carbohydrate	1053:1073	N-linked carbohydrate	1053:1073	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	7	5	from	anti-HCC	1209:1216	arg1	mechanisms					1188:1197	the mechanisms	1184:1197	the mechanisms of DHA in anti-HCC from the angle of glycosylation	1184:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	1	6	theme	L.	181:182	arg1	derivative					133:142	an important derivative	120:142	an important derivative of the herb medicine Artemisia annua L.	120:182	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	1	6	theme	L.	181:182	arg1	activities					255:264	anti-hepatocellular carcinoma (HCC) activities	219:264	anti-hepatocellular carcinoma (HCC) activities	219:264	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	6	7	theme	lectin	960:965	arg1	analysis					972:979	Further lectin immunofluorescence and lectin blot analysis	922:979	analysis	972:979	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	3	8	theme	pharmacology	363:374	arg1	method					376:381	the network pharmacology method	351:381	the network pharmacology method	351:381	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	4	9	theme	biological	692:701	arg1	process					703:709	the biological process	688:709	the biological process of cell-cell adhesion	688:731	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	4	10	theme	anti-HCC	645:652	arg1	related					677:683	related	677:683	related	677:683	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	4	10	theme	anti-HCC	645:652	arg1	effect					654:659	the anti-HCC effect	641:659	the anti-HCC effect of DHA	641:666	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	4	11	theme	DHA	664:666	arg1	related					677:683	related	677:683	related	677:683	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	4	11	theme	DHA	664:666	arg1	effect					654:659	the anti-HCC effect	641:659	the anti-HCC effect of DHA	641:666	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	5	12	theme	N-linked	752:759	arg1	carbohydrate					761:772	N-linked carbohydrate	752:772	N-linked carbohydrate	752:772	β1,6-branching of N-linked carbohydrate as one kind of glycosylation could participate in regulating cell-cell adhesion and has been reported to be overexpressed in HCC cells and tissues.
31926585	2	13	theme	molecular	291:299	arg1	mechanism					301:309	the underlying molecular mechanism	276:309	the underlying molecular mechanism	276:309	However, the underlying molecular mechanism is still unclear.
31926585	2	13	theme	molecular	291:299	arg1	unclear					320:326	unclear	320:326	unclear	320:326	However, the underlying molecular mechanism is still unclear.
31926585	6	14	theme	β1,6-branching	1035:1048	arg1	expression					1021:1030	the expression	1017:1030	the expression of β1,6-branching of N-linked carbohydrate	1017:1073	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	4	15	theme	Functional	600:609	arg1	analysis					620:627	Functional category analysis	600:627	Functional category analysis	600:627	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	3	16	theme	network	355:361	arg1	method					376:381	the network pharmacology method	351:381	the network pharmacology method	351:381	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	2	17	theme	underlying	280:289	arg1	mechanism					301:309	the underlying molecular mechanism	276:309	the underlying molecular mechanism	276:309	However, the underlying molecular mechanism is still unclear.
31926585	2	17	theme	underlying	280:289	arg1	unclear					320:326	unclear	320:326	unclear	320:326	However, the underlying molecular mechanism is still unclear.
31926585	6	18	theme	carbohydrate	1062:1073	arg1	β1,6-branching					1035:1048	β1,6-branching	1035:1048	β1,6-branching of N-linked carbohydrate	1035:1073	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	0	19	theme	pharmacology-based	8:25	arg1	analysis					27:34	Network pharmacology-based analysis	0:34	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.	0:115	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.
31926585	6	20	theme	N-linked	1053:1060	arg1	carbohydrate					1062:1073	N-linked carbohydrate	1053:1073	N-linked carbohydrate	1053:1073	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	7	21	theme	DHA	1202:1204	arg1	mechanisms					1188:1197	the mechanisms	1184:1197	the mechanisms of DHA in anti-HCC from the angle of glycosylation	1184:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	7	22	theme	glycosylation	1236:1248	arg1	angle					1227:1231	the angle	1223:1231	the angle of glycosylation	1223:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	3	23	theme	DHA	438:440	arg1	network					427:433	the ingredient-target network	405:433	the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected	405:597	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	0	24	theme	Network	0:6	arg1	analysis					27:34	Network pharmacology-based analysis	0:34	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.	0:115	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.
31926585	6	25	theme	lectin	930:935	arg1	immunofluorescence					937:954	Further lectin immunofluorescence and lectin blot analysis	922:979	immunofluorescence	937:954	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	5	26	theme	HCC	899:901	arg1	cells					903:907	HCC cells	899:907	HCC cells	899:907	β1,6-branching of N-linked carbohydrate as one kind of glycosylation could participate in regulating cell-cell adhesion and has been reported to be overexpressed in HCC cells and tissues.
31926585	4	27	theme	category	611:618	arg1	analysis					620:627	Functional category analysis	600:627	Functional category analysis	600:627	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	5	28	theme	carbohydrate	761:772	arg1	β1,6-branching					734:747	β1,6-branching	734:747	β1,6-branching of N-linked carbohydrate as one kind of glycosylation	734:801	β1,6-branching of N-linked carbohydrate as one kind of glycosylation could participate in regulating cell-cell adhesion and has been reported to be overexpressed in HCC cells and tissues.
31926585	3	29	used	used	387:390	arg2	method					376:381	the network pharmacology method	351:381	the network pharmacology method	351:381	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	7	30	from	angle	1227:1231	arg1	DHA					1202:1204	DHA	1202:1204	DHA in anti-HCC from the angle of glycosylation	1202:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	7	30	from	angle	1227:1231	arg1	mechanisms					1188:1197	the mechanisms	1184:1197	the mechanisms of DHA in anti-HCC from the angle of glycosylation	1184:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	3	31	theme	anti-HCC	471:478	arg1	effect					480:485	the anti-HCC effect	467:485	the anti-HCC effect	467:485	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	7	32	theme	scientific	1144:1153	arg1	basis					1155:1159	a scientific basis	1142:1159	a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation	1142:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	4	33	theme	cell-cell	714:722	arg1	adhesion					724:731	cell-cell adhesion	714:731	cell-cell adhesion	714:731	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	1	34	theme	important	123:131	arg1	derivative					133:142	an important derivative	120:142	an important derivative of the herb medicine Artemisia annua L.	120:182	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	1	34	theme	important	123:131	arg1	activities					255:264	anti-hepatocellular carcinoma (HCC) activities	219:264	anti-hepatocellular carcinoma (HCC) activities	219:264	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	5	35	theme	glycosylation	789:801	arg1	kind					781:784	one kind	777:784	one kind of glycosylation	777:801	β1,6-branching of N-linked carbohydrate as one kind of glycosylation could participate in regulating cell-cell adhesion and has been reported to be overexpressed in HCC cells and tissues.
31926585	5	36	theme	cell-cell	835:843	arg1	adhesion					845:852	cell-cell adhesion	835:852	cell-cell adhesion	835:852	β1,6-branching of N-linked carbohydrate as one kind of glycosylation could participate in regulating cell-cell adhesion and has been reported to be overexpressed in HCC cells and tissues.
31926585	1	37	theme	anti-hepatocellular	219:237	arg1	HCC					250:252	HCC	250:252	HCC	250:252	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	1	37	theme	anti-hepatocellular	219:237	arg1	carcinoma					239:247	anti-hepatocellular carcinoma	219:247	anti-hepatocellular carcinoma (HCC) activities	219:264	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	0	38	theme	mechanisms	39:48	arg1	analysis					27:34	Network pharmacology-based analysis	0:34	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.	0:115	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.
31926585	1	39	theme	carcinoma	239:247	arg1	derivative					133:142	an important derivative	120:142	an important derivative of the herb medicine Artemisia annua L.	120:182	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	1	39	theme	carcinoma	239:247	arg1	activities					255:264	anti-hepatocellular carcinoma (HCC) activities	219:264	anti-hepatocellular carcinoma (HCC) activities	219:264	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	0	40	theme	anti-hepatocellular	57:75	arg1	effect					87:92	the anti-hepatocellular carcinoma effect	53:92	the anti-hepatocellular carcinoma effect	53:92	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.
31926585	6	41	theme	Further	922:928	arg1	immunofluorescence					937:954	Further lectin immunofluorescence and lectin blot analysis	922:979	immunofluorescence	937:954	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	3	42	theme	ingredient-target	409:425	arg1	network					427:433	the ingredient-target network	405:433	the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected	405:597	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	7	43	from	mechanisms	1188:1197	arg1	anti-HCC					1209:1216	anti-HCC	1209:1216	anti-HCC	1209:1216	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	7	43	from	mechanisms	1188:1197	arg1	angle					1227:1231	the angle	1223:1231	the angle of glycosylation	1223:1248	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	3	44	dep	responsible	451:461	arg1	network					427:433	the ingredient-target network	405:433	the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected	405:597	In the present study, the network pharmacology method was used to construct the ingredient-target network of DHA that was responsible for the anti-HCC effect and 11 targets including ALB, ATP5A1, CCT3, CLIC1, ENO1, HSPA8, HSPB1, NPM1, PPIA, PRDX1, and ZYX were selected.
31926585	6	45	theme	MGAT5	1111:1115	arg1	transcription					1094:1106	the transcription	1090:1106	the transcription of MGAT5	1090:1115	Further lectin immunofluorescence and lectin blot analysis showed that DHA could down-regulate the expression of β1,6-branching of N-linked carbohydrate by suppressing the transcription of MGAT5.
31926585	7	46	from	DHA	1202:1204	arg1	anti-HCC					1209:1216	anti-HCC	1209:1216	anti-HCC	1209:1216	This study will provide a scientific basis for the elucidation of the mechanisms of DHA in anti-HCC from the angle of glycosylation.
31926585	4	47	theme	adhesion	724:731	arg1	process					703:709	the biological process	688:709	the biological process of cell-cell adhesion	688:731	Functional category analysis showed that the anti-HCC effect of DHA might be related to the biological process of cell-cell adhesion.
31926585	1	48	theme	herb	151:154	arg1	L.					181:182	the herb medicine Artemisia annua L.	147:182	the herb medicine Artemisia annua L.	147:182	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	0	49	theme	effect	87:92	arg1	mechanisms					39:48	mechanisms	39:48	mechanisms of the anti-hepatocellular carcinoma effect	39:92	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.
31926585	5	50	link	N-linked	752:759	arg1	carbohydrate					761:772	N-linked carbohydrate	752:772	N-linked carbohydrate	752:772	β1,6-branching of N-linked carbohydrate as one kind of glycosylation could participate in regulating cell-cell adhesion and has been reported to be overexpressed in HCC cells and tissues.
31926585	1	51	theme	medicine	156:163	arg1	L.					181:182	the herb medicine Artemisia annua L.	147:182	the herb medicine Artemisia annua L.	147:182	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31926585	0	52	theme	carcinoma	77:85	arg1	effect					87:92	the anti-hepatocellular carcinoma effect	53:92	the anti-hepatocellular carcinoma effect	53:92	Network pharmacology-based analysis of mechanisms of the anti-hepatocellular carcinoma effect by dihydroartemisinin.
31926585	1	53	theme	Artemisia	165:173	arg1	L.					181:182	the herb medicine Artemisia annua L.	147:182	the herb medicine Artemisia annua L.	147:182	As an important derivative of the herb medicine Artemisia annua L., dihydroartemisinin (DHA) exhibits anti-hepatocellular carcinoma (HCC) activities.
31511323	7	0	theme	cell	1184:1187	arg1	surface					1189:1195	the cell surface	1180:1195	the cell surface	1180:1195	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	1	1	theme	pore-forming	257:268	arg1	subunit					272:278	a pore-forming α subunit	255:278	a pore-forming α subunit	255:278	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	11	2	from	defective	1747:1755	arg1	arrhythmias					1778:1788	inherited cardiac arrhythmias	1760:1788	inherited cardiac arrhythmias	1760:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	6	3	theme	apical	1120:1125	arg1	membrane					1134:1141	the apical plasma membrane	1116:1141	the apical plasma membrane	1116:1141	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	11	4	theme	cardiac	1770:1776	arg1	arrhythmias					1778:1788	inherited cardiac arrhythmias	1760:1788	inherited cardiac arrhythmias	1760:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	6	5	theme	β2	1098:1099	arg1	trafficking					1101:1111	efficient β2 trafficking	1088:1111	efficient β2 trafficking to the apical plasma membrane	1088:1141	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	10	6	theme	intact	1509:1514	arg1	site					1530:1533	a single intact glycosylation site	1500:1533	a single intact glycosylation site	1500:1533	Interestingly, β2 with a single intact glycosylation site was as effective as the WT in promoting NaV1.5 surface localization.
31511323	11	7	theme	NaV1.5	1714:1719	arg1	localization					1698:1709	surface localization	1690:1709	surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias	1690:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	3	8	theme	channel	551:557	arg1	gene					524:527	the NaV1.5-encoding gene	504:527	the NaV1.5-encoding gene	504:527	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	8	theme	channel	551:557	arg1	subunit					561:567	sodium voltage-gated channel α subunit 5	530:569	sodium voltage-gated channel α subunit 5 (SCN5A)	530:577	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	8	theme	channel	551:557	arg1	SCN5A					572:576	SCN5A	572:576	SCN5A	572:576	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	8	9	dep	YFP-tagged	1292:1301	arg1	nonglycosylated					1304:1318	nonglycosylated	1304:1318	nonglycosylated	1304:1318	YFP-tagged, nonglycosylated β2 displayed mobility kinetics in the plane of the membrane similar to that of WT β2.
31511323	10	10	with	β2	1492:1493	arg1	site					1530:1533	a single intact glycosylation site	1500:1533	a single intact glycosylation site	1500:1533	Interestingly, β2 with a single intact glycosylation site was as effective as the WT in promoting NaV1.5 surface localization.
31511323	3	11	theme	sodium	530:535	arg1	channel					551:557	sodium voltage-gated channel	530:557	sodium voltage-gated channel α subunit 5 (SCN5A)	530:577	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	8	12	theme	membrane	1371:1378	arg1	plane					1358:1362	the plane	1354:1362	the plane of the membrane similar to that of WT β2	1354:1403	YFP-tagged, nonglycosylated β2 displayed mobility kinetics in the plane of the membrane similar to that of WT β2.
31511323	5	13	theme	Madin-Darby	792:802	arg1	kidney					811:816	Madin-Darby canine kidney	792:816	polarized Madin-Darby canine kidney cells	782:822	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	11	14	gly	glycosylation	1654:1666	arg1	NaV1.5					1714:1719	NaV1.5	1714:1719	NaV1.5	1714:1719	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	11	14	gly	glycosylation	1654:1666	arg1	property					1724:1731	a property	1722:1731	a property that is often defective in inherited cardiac arrhythmias	1722:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	11	14	gly	glycosylation	1654:1666	arg1	β2					1671:1672	β2	1671:1672	β2	1671:1672	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	11	14	gly	glycosylation	1654:1666	arg1	defective					1747:1755	defective	1747:1755	defective	1747:1755	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	11	14	gly	glycosylation	1654:1666	arg1	surface					1690:1696	surface localization	1690:1709	surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias	1690:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	11	15	theme	N-linked	1645:1652	arg1	glycosylation					1654:1666	N-linked glycosylation	1645:1666	N-linked glycosylation of β2	1645:1672	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	1	16	theme	voltage-gated	142:154	arg1	critical					174:181	critical	174:181	critical	174:181	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	1	16	theme	voltage-gated	142:154	arg1	channel					163:169	The voltage-gated sodium channel	138:169	The voltage-gated sodium channel	138:169	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	9	17	theme	surface	1445:1451	arg1	localization					1453:1464	surface localization	1445:1464	surface localization of NaV1.5	1445:1474	However, it was defective in promoting surface localization of NaV1.5.
31511323	11	18	from	arrhythmias	1778:1788	arg1	NaV1.5					1714:1719	NaV1.5	1714:1719	NaV1.5	1714:1719	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	11	18	from	arrhythmias	1778:1788	arg1	property					1724:1731	a property	1722:1731	a property that is often defective in inherited cardiac arrhythmias	1722:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	11	18	from	arrhythmias	1778:1788	arg1	defective					1747:1755	defective	1747:1755	defective	1747:1755	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	4	19	theme	cell	722:725	arg1	localization					735:746	proper NaV1.5 cell surface localization	708:746	proper NaV1.5 cell surface localization	708:746	Here, we investigated the mechanisms that regulate β2 trafficking and how they may determine proper NaV1.5 cell surface localization.
31511323	6	20	gly	glycosylation	1058:1070	arg1	β2					1098:1099	efficient β2 trafficking	1088:1111	efficient β2 trafficking to the apical plasma membrane	1088:1141	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	3	21	theme	adult	449:453	arg1	heart					461:465	the adult human heart	445:465	the adult human heart	445:465	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	22	theme	major	426:430	arg1	NaV1.5					470:475	NaV1.5	470:475	NaV1.5	470:475	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	22	theme	major	426:430	arg1	isoform					434:440	The major α isoform	422:440	The major α isoform in the adult human heart	422:465	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	0	23	theme	NaV1.5/β2	104:112	arg1	trafficking					89:99	efficient trafficking	79:99	efficient trafficking of NaV1.5/β2 to the plasma membrane	79:135	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	7	24	theme	that	1277:1280	arg1	one-third					1264:1272	one-third	1264:1272	one-third	1264:1272	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	7	24	theme	that	1277:1280	arg1	that					1277:1280	that	1277:1280	that	1277:1280	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	10	25	gly	glycosylation	1516:1528	arg2	site					1530:1533	a single intact glycosylation site	1500:1533	a single intact glycosylation site	1500:1533	Interestingly, β2 with a single intact glycosylation site was as effective as the WT in promoting NaV1.5 surface localization.
31511323	2	26	theme	cell	380:383	arg1	expression					393:402	cell surface expression	380:402	cell surface expression of the α subunit	380:419	It has been shown previously that the associated β2 subunits promote cell surface expression of the α subunit.
31511323	5	27	theme	polarized	782:790	arg1	cells					818:822	polarized Madin-Darby canine kidney cells	782:822	polarized Madin-Darby canine kidney cells	782:822	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	7	28	theme	one-third	1264:1272	arg1	rate					1237:1240	a rate	1235:1240	a rate of only approximately one-third of that of WT β2	1235:1289	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	4	29	theme	proper	708:713	arg1	localization					735:746	proper NaV1.5 cell surface localization	708:746	proper NaV1.5 cell surface localization	708:746	Here, we investigated the mechanisms that regulate β2 trafficking and how they may determine proper NaV1.5 cell surface localization.
31511323	2	30	theme	subunit	413:419	arg1	expression					393:402	cell surface expression	380:402	cell surface expression of the α subunit	380:419	It has been shown previously that the associated β2 subunits promote cell surface expression of the α subunit.
31511323	5	31	theme	canine	804:809	arg1	kidney					811:816	Madin-Darby canine kidney	792:816	polarized Madin-Darby canine kidney cells	782:822	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	1	32	theme	associated	288:297	arg1	subunits					301:308	two associated β subunits	284:308	two associated β subunits	284:308	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	8	33	theme	mobility	1333:1340	arg1	kinetics					1342:1349	mobility kinetics	1333:1349	mobility kinetics	1333:1349	YFP-tagged, nonglycosylated β2 displayed mobility kinetics in the plane of the membrane similar to that of WT β2.
31511323	10	34	theme	NaV1.5	1575:1580	arg1	localization					1590:1601	NaV1.5 surface localization	1575:1601	NaV1.5 surface localization	1575:1601	Interestingly, β2 with a single intact glycosylation site was as effective as the WT in promoting NaV1.5 surface localization.
31511323	0	35	theme	sodium	37:42	arg1	channel					44:50	voltage-gated sodium channel	23:50	the voltage-gated sodium channel β2 subunit	19:61	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	3	36	theme	inherited	592:600	arg1	arrhythmias					602:612	inherited arrhythmias	592:612	inherited arrhythmias	592:612	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	0	37	theme	β2	52:53	arg1	subunit					55:61	the voltage-gated sodium channel β2 subunit	19:61	the voltage-gated sodium channel β2 subunit	19:61	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	6	38	theme	plasma	1127:1132	arg1	membrane					1134:1141	the apical plasma membrane	1116:1141	the apical plasma membrane	1116:1141	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	3	39	theme	human	455:459	arg1	heart					461:465	the adult human heart	445:465	the adult human heart	445:465	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	7	40	theme	Golgi	1214:1218	arg1	compartment					1220:1230	the Golgi compartment	1210:1230	the Golgi compartment	1210:1230	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	3	41	theme	germline	482:489	arg1	mutations					491:499	germline mutations	482:499	germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A),	482:578	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	5	42	theme	heterologous	755:766	arg1	expression					768:777	heterologous expression	755:777	heterologous expression in polarized Madin-Darby canine kidney cells	755:822	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	7	43	theme	nonglycosylated	1148:1162	arg1	variant					1164:1170	The nonglycosylated variant	1144:1170	The nonglycosylated variant	1144:1170	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	2	44	theme	associated	349:358	arg1	subunits					363:370	the associated β2 subunits	345:370	the associated β2 subunits	345:370	It has been shown previously that the associated β2 subunits promote cell surface expression of the α subunit.
31511323	6	45	theme	endoplasmic	1010:1020	arg1	reticulum					1022:1030	the endoplasmic reticulum	1006:1030	the endoplasmic reticulum	1006:1030	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	3	46	theme	NaV1.5-encoding	508:522	arg1	gene					524:527	the NaV1.5-encoding gene	504:527	the NaV1.5-encoding gene	504:527	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	46	theme	NaV1.5-encoding	508:522	arg1	subunit					561:567	sodium voltage-gated channel α subunit 5	530:569	sodium voltage-gated channel α subunit 5 (SCN5A)	530:577	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	1	47	theme	α	270:270	arg1	subunit					272:278	a pore-forming α subunit	255:278	a pore-forming α subunit	255:278	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	3	48	from	mutations	491:499	arg1	gene					524:527	the NaV1.5-encoding gene	504:527	the NaV1.5-encoding gene	504:527	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	48	from	mutations	491:499	arg1	subunit					561:567	sodium voltage-gated channel α subunit 5	530:569	sodium voltage-gated channel α subunit 5 (SCN5A)	530:577	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	10	49	theme	glycosylation	1516:1528	arg1	site					1530:1533	a single intact glycosylation site	1500:1533	a single intact glycosylation site	1500:1533	Interestingly, β2 with a single intact glycosylation site was as effective as the WT in promoting NaV1.5 surface localization.
31511323	3	50	theme	voltage-gated	537:549	arg1	channel					551:557	sodium voltage-gated channel	530:557	sodium voltage-gated channel α subunit 5 (SCN5A)	530:577	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	6	51	theme	efficient	1088:1096	arg1	trafficking					1101:1111	efficient β2 trafficking	1088:1111	efficient β2 trafficking to the apical plasma membrane	1088:1141	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	10	52	theme	single	1502:1507	arg1	site					1530:1533	a single intact glycosylation site	1500:1533	a single intact glycosylation site	1500:1533	Interestingly, β2 with a single intact glycosylation site was as effective as the WT in promoting NaV1.5 surface localization.
31511323	0	53	theme	plasma	121:126	arg1	membrane					128:135	the plasma membrane	117:135	the plasma membrane	117:135	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	5	54	theme	kidney	811:816	arg1	cells					818:822	polarized Madin-Darby canine kidney cells	782:822	polarized Madin-Darby canine kidney cells	782:822	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	8	55	theme	similar	1380:1386	arg1	membrane					1371:1378	the membrane	1367:1378	the membrane similar to that of WT β2	1367:1403	YFP-tagged, nonglycosylated β2 displayed mobility kinetics in the plane of the membrane similar to that of WT β2.
31511323	1	56	theme	cardiomyocyte	187:199	arg1	function					201:208	cardiomyocyte function	187:208	cardiomyocyte function	187:208	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	3	57	theme	α	559:559	arg1	gene					524:527	the NaV1.5-encoding gene	504:527	the NaV1.5-encoding gene	504:527	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	57	theme	α	559:559	arg1	subunit					561:567	sodium voltage-gated channel α subunit 5	530:569	sodium voltage-gated channel α subunit 5 (SCN5A)	530:577	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	57	theme	α	559:559	arg1	SCN5A					572:576	SCN5A	572:576	SCN5A	572:576	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	5	58	gly	N-glycosylated	844:857	arg2	residues					883:890	residues 42, 66, and 74	883:905	residues 42, 66, and 74	883:905	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	5	58	gly	N-glycosylated	844:857	arg1	β2					838:839	β2	838:839	β2	838:839	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	8	59	theme	WT	1399:1400	arg1	β2					1402:1403	WT β2	1399:1403	WT β2	1399:1403	YFP-tagged, nonglycosylated β2 displayed mobility kinetics in the plane of the membrane similar to that of WT β2.
31511323	4	60	theme	β2	666:667	arg1	trafficking					669:679	β2 trafficking	666:679	β2 trafficking	666:679	Here, we investigated the mechanisms that regulate β2 trafficking and how they may determine proper NaV1.5 cell surface localization.
31511323	11	61	theme	β2	1671:1672	arg1	glycosylation					1654:1666	N-linked glycosylation	1645:1666	N-linked glycosylation of β2	1645:1672	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	7	62	theme	WT	1285:1286	arg1	β2					1288:1289	WT β2	1285:1289	WT β2	1285:1289	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	0	63	theme	efficient	79:87	arg1	trafficking					89:99	efficient trafficking	79:99	efficient trafficking of NaV1.5/β2 to the plasma membrane	79:135	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	5	64	from	expression	768:777	arg1	cells					818:822	polarized Madin-Darby canine kidney cells	782:822	polarized Madin-Darby canine kidney cells	782:822	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	1	65	theme	sodium	156:161	arg1	critical					174:181	critical	174:181	critical	174:181	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	1	65	theme	sodium	156:161	arg1	channel					163:169	The voltage-gated sodium channel	138:169	The voltage-gated sodium channel	138:169	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	11	66	theme	surface	1690:1696	arg1	localization					1698:1709	surface localization	1690:1709	surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias	1690:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	4	67	theme	NaV1.5	715:720	arg1	localization					735:746	proper NaV1.5 cell surface localization	708:746	proper NaV1.5 cell surface localization	708:746	Here, we investigated the mechanisms that regulate β2 trafficking and how they may determine proper NaV1.5 cell surface localization.
31511323	9	68	theme	NaV1.5	1469:1474	arg1	localization					1453:1464	surface localization	1445:1464	surface localization of NaV1.5	1445:1474	However, it was defective in promoting surface localization of NaV1.5.
31511323	11	69	link	N-linked	1645:1652	arg1	glycosylation					1654:1666	N-linked glycosylation	1645:1666	N-linked glycosylation of β2	1645:1672	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	4	70	theme	surface	727:733	arg1	localization					735:746	proper NaV1.5 cell surface localization	708:746	proper NaV1.5 cell surface localization	708:746	Here, we investigated the mechanisms that regulate β2 trafficking and how they may determine proper NaV1.5 cell surface localization.
31511323	2	71	theme	surface	385:391	arg1	expression					393:402	cell surface expression	380:402	cell surface expression of the α subunit	380:419	It has been shown previously that the associated β2 subunits promote cell surface expression of the α subunit.
31511323	5	72	from	residues	883:890	arg1	N-glycosylated					844:857	N-glycosylated	844:857	N-glycosylated	844:857	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	8	73	theme	YFP-tagged	1292:1301	arg1	β2					1320:1321	YFP-tagged, nonglycosylated β2	1292:1321	YFP-tagged, nonglycosylated β2	1292:1321	YFP-tagged, nonglycosylated β2 displayed mobility kinetics in the plane of the membrane similar to that of WT β2.
31511323	0	74	theme	voltage-gated	23:35	arg1	channel					44:50	voltage-gated sodium channel	23:50	the voltage-gated sodium channel β2 subunit	19:61	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	6	75	link	N-linked	1049:1056	arg1	glycosylation					1058:1070	N-linked glycosylation	1049:1070	N-linked glycosylation	1049:1070	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	7	76	gly	nonglycosylated	1148:1162	arg1	variant					1164:1170	The nonglycosylated variant	1144:1170	The nonglycosylated variant	1144:1170	The nonglycosylated variant reached the cell surface by bypassing the Golgi compartment at a rate of only approximately one-third of that of WT β2.
31511323	10	77	theme	surface	1582:1588	arg1	localization					1590:1601	NaV1.5 surface localization	1575:1601	NaV1.5 surface localization	1575:1601	Interestingly, β2 with a single intact glycosylation site was as effective as the WT in promoting NaV1.5 surface localization.
31511323	0	78	theme	channel	44:50	arg1	subunit					55:61	the voltage-gated sodium channel β2 subunit	19:61	the voltage-gated sodium channel β2 subunit	19:61	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	1	79	theme	β	299:299	arg1	subunits					301:308	two associated β subunits	284:308	two associated β subunits	284:308	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	0	80	gly	N-Glycosylation	0:14	arg1	subunit					55:61	the voltage-gated sodium channel β2 subunit	19:61	the voltage-gated sodium channel β2 subunit	19:61	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	6	81	theme	nonglycosylated	964:978	arg1	β2					980:981	fully nonglycosylated β2	958:981	fully nonglycosylated β2	958:981	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	5	82	gly	sialylated	917:926	arg2	Asn-42					936:941	Asn-42	936:941	Asn-42	936:941	Using heterologous expression in polarized Madin-Darby canine kidney cells, we show that β2 is N-glycosylated in vivo and in vitro at residues 42, 66, and 74, becoming sialylated only at Asn-42.
31511323	6	83	gly	nonglycosylated	964:978	arg1	β2					980:981	fully nonglycosylated β2	958:981	fully nonglycosylated β2	958:981	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	3	84	from	isoform	434:440	arg1	heart					461:465	the adult human heart	445:465	the adult human heart	445:465	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	0	85	theme	subunit	55:61	arg1	N-Glycosylation					0:14	N-Glycosylation	0:14	N-Glycosylation of the voltage-gated sodium channel β2 subunit	0:61	N-Glycosylation of the voltage-gated sodium channel β2 subunit is required for efficient trafficking of NaV1.5/β2 to the plasma membrane.
31511323	11	86	theme	inherited	1760:1768	arg1	arrhythmias					1778:1788	inherited cardiac arrhythmias	1760:1788	inherited cardiac arrhythmias	1760:1788	In conclusion, our results indicate that N-linked glycosylation of β2 is required for surface localization of NaV1.5, a property that is often defective in inherited cardiac arrhythmias.
31511323	6	87	theme	N-linked	1049:1056	arg1	glycosylation					1058:1070	N-linked glycosylation	1049:1070	N-linked glycosylation	1049:1070	We found that fully nonglycosylated β2 was mostly retained in the endoplasmic reticulum, indicating that N-linked glycosylation is required for efficient β2 trafficking to the apical plasma membrane.
31511323	1	88	theme	protein	228:234	arg1	complex					236:242	a protein complex	226:242	a protein complex comprising a pore-forming α subunit and two associated β subunits	226:308	The voltage-gated sodium channel is critical for cardiomyocyte function and consists of a protein complex comprising a pore-forming α subunit and two associated β subunits.
31511323	3	89	theme	α	432:432	arg1	NaV1.5					470:475	NaV1.5	470:475	NaV1.5	470:475	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	3	89	theme	α	432:432	arg1	isoform					434:440	The major α isoform	422:440	The major α isoform in the adult human heart	422:465	The major α isoform in the adult human heart is NaV1.5, and germline mutations in the NaV1.5-encoding gene, sodium voltage-gated channel α subunit 5 (SCN5A), often cause inherited arrhythmias.
31511323	2	90	theme	β2	360:361	arg1	subunits					363:370	the associated β2 subunits	345:370	the associated β2 subunits	345:370	It has been shown previously that the associated β2 subunits promote cell surface expression of the α subunit.
30619781	5	0	theme	NleB1	848:852	arg1	glycosylation					854:866	NleB1 glycosylation	848:866	NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein	848:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	6	1	theme	ATCC	1021:1024	arg1	replication					1032:1042	Salmonella enterica strain ATCC 14028 replication	994:1042	Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells	994:1073	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	7	2	theme	in	1149:1150	arg1	cross-reactivity					1158:1173	in vitro cross-reactivity	1149:1173	in vitro cross-reactivity	1149:1173	Neither inhibitor was significantly toxic to mammalian cells, nor showed in vitro cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	3	3	theme	high-throughput	571:585	arg1	assays					597:602	high-throughput screening assays	571:602	high-throughput screening assays	571:602	We conducted high-throughput screening assays to identify small molecules that inhibit NleB/SseK activity.
30619781	6	4	theme	Salmonella	994:1003	arg1	replication					1032:1042	Salmonella enterica strain ATCC 14028 replication	994:1042	Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells	994:1073	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	2	5	theme	N-acetylglucosaminyltransferase	525:555	arg1	activity					490:497	the activity	486:497	the activity of the mammalian O-linked N-acetylglucosaminyltransferase	486:555	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	2	6	from	activity	490:497	arg1	distinct					472:479	distinct	472:479	distinct	472:479	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	2	7	theme	guanidinium	403:413	arg1	groups					415:420	the guanidinium groups	399:420	the guanidinium groups of arginines, which are poor nucleophiles	399:462	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	2	7	theme	guanidinium	403:413	arg1	nucleophiles					451:462	poor nucleophiles	446:462	poor nucleophiles	446:462	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	2	7	theme	guanidinium	403:413	arg1	arginines					425:433	arginines	425:433	arginines	425:433	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	1	8	theme	host	311:314	arg1	substrates					316:325	host substrates	311:325	host substrates on arginine residues	311:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	5	9	theme	mammalian	806:814	arg1	cells					816:820	cultured mammalian cells	797:820	cultured mammalian cells	797:820	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	1	10	theme	enteropathogenic	76:91	arg1	proteins					186:193	the Salmonella enterica SseK proteins	157:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	10	theme	enteropathogenic	76:91	arg1	proteins					137:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins	72:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	10	theme	enteropathogenic	76:91	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	3	11	theme	NleB/SseK	645:653	arg1	activity					655:662	NleB/SseK activity	645:662	NleB/SseK activity	645:662	We conducted high-throughput screening assays to identify small molecules that inhibit NleB/SseK activity.
30619781	7	12	dep	in	1149:1150	arg1	vitro					1152:1156	vitro	1152:1156	vitro	1152:1156	Neither inhibitor was significantly toxic to mammalian cells, nor showed in vitro cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	5	13	theme	compounds	784:792	arg1	Addition					766:773	Addition	766:773	Addition of these compounds to cultured mammalian cells	766:820	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	1	14	dep	Salmonella	161:170	arg1	enterica					172:179	enterica	172:179	enterica	172:179	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	15	theme	enterohemorrhagic	97:113	arg1	proteins					186:193	the Salmonella enterica SseK proteins	157:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	15	theme	enterohemorrhagic	97:113	arg1	proteins					137:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins	72:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	15	theme	enterohemorrhagic	97:113	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	4	16	theme	SseK2	748:752	arg1	activities					754:763	SseK2 activities	748:763	SseK2 activities	748:763	Two compounds, 100066N and 102644N, both significantly inhibited NleB1, SseK1, and SseK2 activities.
30619781	1	17	theme	type	199:202	arg1	system					218:223	type III secretion system	199:223	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	8	18	dep	compounds	1242:1250	arg1	These					1236:1240	These	1236:1240	These	1236:1240	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	7	19	theme	O-linked	1194:1201	arg1	N-acetylglucosaminyltransferase					1203:1233	the mammalian O-linked N-acetylglucosaminyltransferase	1180:1233	the mammalian O-linked N-acetylglucosaminyltransferase	1180:1233	Neither inhibitor was significantly toxic to mammalian cells, nor showed in vitro cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	1	20	theme	Escherichia	115:125	arg1	proteins					186:193	the Salmonella enterica SseK proteins	157:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	20	theme	Escherichia	115:125	arg1	proteins					137:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins	72:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	20	theme	Escherichia	115:125	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	5	21	theme	factor	890:895	arg1	protein					937:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	8	22	contain	have	1318:1321	arg1	derivatives					1255:1265	derivatives	1255:1265	derivatives	1255:1265	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	8	22	contain	have	1318:1321	arg2	utility					1323:1329	utility	1323:1329	utility	1323:1329	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	8	22	contain	have	1318:1321	arg1	compounds					1242:1250	compounds	1242:1250	compounds	1242:1250	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	8	22	contain	have	1318:1321	arg2	strategy					1370:1377	a potential alternative therapeutic strategy	1334:1377	a potential alternative therapeutic strategy to antibiotics	1334:1392	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	1	23	theme	secretion	208:216	arg1	system					218:223	type III secretion system	199:223	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	0	24	theme	High-Throughput	0:14	arg1	Screening					16:24	High-Throughput Screening	0:24	High-Throughput Screening for Bacterial Glycosyltransferase Inhibitors	0:69	High-Throughput Screening for Bacterial Glycosyltransferase Inhibitors.
30619781	1	25	theme	arginine	330:337	arg1	residues					339:346	arginine residues	330:346	arginine residues	330:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	2	26	link	O-linked	516:523	arg1	N-acetylglucosaminyltransferase					525:555	the mammalian O-linked N-acetylglucosaminyltransferase	502:555	the mammalian O-linked N-acetylglucosaminyltransferase	502:555	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	1	27	theme	NleB	132:135	arg1	proteins					186:193	the Salmonella enterica SseK proteins	157:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	27	theme	NleB	132:135	arg1	proteins					137:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins	72:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	27	theme	NleB	132:135	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	7	28	theme	mammalian	1184:1192	arg1	N-acetylglucosaminyltransferase					1203:1233	the mammalian O-linked N-acetylglucosaminyltransferase	1180:1233	the mammalian O-linked N-acetylglucosaminyltransferase	1180:1233	Neither inhibitor was significantly toxic to mammalian cells, nor showed in vitro cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	1	29	theme	system	218:223	arg1	proteins					137:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins	72:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	29	theme	system	218:223	arg1	proteins					186:193	the Salmonella enterica SseK proteins	157:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	29	theme	system	218:223	arg1	enzymes					272:278	glycosyltransferase enzymes	252:278	glycosyltransferase enzymes	252:278	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	29	theme	system	218:223	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	0	30	theme	Bacterial	30:38	arg1	Inhibitors					60:69	Bacterial Glycosyltransferase Inhibitors	30:69	Bacterial Glycosyltransferase Inhibitors	30:69	High-Throughput Screening for Bacterial Glycosyltransferase Inhibitors.
30619781	5	31	theme	receptor	897:904	arg1	protein					937:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	1	32	from	substrates	316:325	arg1	residues					339:346	arginine residues	330:346	arginine residues	330:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	5	33	theme	DEATH	924:928	arg1	protein					937:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	5	34	theme	1-associated	911:922	arg1	protein					937:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	5	35	gly	glycosylation	854:866	arg1	protein					937:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	3	36	theme	screening	587:595	arg1	assays					597:602	high-throughput screening assays	571:602	high-throughput screening assays	571:602	We conducted high-throughput screening assays to identify small molecules that inhibit NleB/SseK activity.
30619781	5	37	theme	domain	930:935	arg1	protein					937:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	2	38	theme	O-linked	516:523	arg1	N-acetylglucosaminyltransferase					525:555	the mammalian O-linked N-acetylglucosaminyltransferase	502:555	the mammalian O-linked N-acetylglucosaminyltransferase	502:555	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	8	39	theme	glycosyltransferases	1443:1462	arg1	study					1424:1428	further the study	1412:1428	further the study of bacterial glycosyltransferases	1412:1462	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	5	40	theme	cultured	797:804	arg1	cells					816:820	cultured mammalian cells	797:820	cultured mammalian cells	797:820	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	5	41	theme	protein	937:943	arg1	glycosylation					854:866	NleB1 glycosylation	848:866	NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein	848:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	0	42	theme	Glycosyltransferase	40:58	arg1	Inhibitors					60:69	Bacterial Glycosyltransferase Inhibitors	30:69	Bacterial Glycosyltransferase Inhibitors	30:69	High-Throughput Screening for Bacterial Glycosyltransferase Inhibitors.
30619781	6	43	theme	macrophage-like	1053:1067	arg1	cells					1069:1073	mouse macrophage-like cells	1047:1073	mouse macrophage-like cells	1047:1073	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	2	44	theme	mammalian	506:514	arg1	N-acetylglucosaminyltransferase					525:555	the mammalian O-linked N-acetylglucosaminyltransferase	502:555	the mammalian O-linked N-acetylglucosaminyltransferase	502:555	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	7	45	link	O-linked	1194:1201	arg1	N-acetylglucosaminyltransferase					1203:1233	the mammalian O-linked N-acetylglucosaminyltransferase	1180:1233	the mammalian O-linked N-acetylglucosaminyltransferase	1180:1233	Neither inhibitor was significantly toxic to mammalian cells, nor showed in vitro cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	5	46	theme	type	906:909	arg1	protein					937:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	8	47	theme	alternative	1346:1356	arg1	utility					1323:1329	utility	1323:1329	utility	1323:1329	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	8	47	theme	alternative	1346:1356	arg1	strategy					1370:1377	a potential alternative therapeutic strategy	1334:1377	a potential alternative therapeutic strategy to antibiotics	1334:1392	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	5	48	theme	tumor	875:879	arg1	factor					890:895	tumor necrosis factor	875:895	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	6	49	theme	mouse	1047:1051	arg1	cells					1069:1073	mouse macrophage-like cells	1047:1073	mouse macrophage-like cells	1047:1073	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	5	50	theme	necrosis	881:888	arg1	factor					890:895	tumor necrosis factor	875:895	the tumor necrosis factor receptor type 1-associated DEATH domain protein	871:943	Addition of these compounds to cultured mammalian cells was sufficient to inhibit NleB1 glycosylation of the tumor necrosis factor receptor type 1-associated DEATH domain protein.
30619781	2	51	theme	poor	446:449	arg1	nucleophiles					451:462	poor nucleophiles	446:462	poor nucleophiles	446:462	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	2	51	theme	poor	446:449	arg1	arginines					425:433	arginines	425:433	arginines	425:433	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	6	52	from	replication	1032:1042	arg1	cells					1069:1073	mouse macrophage-like cells	1047:1073	mouse macrophage-like cells	1047:1073	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	6	53	theme	strain	1014:1019	arg1	replication					1032:1042	Salmonella enterica strain ATCC 14028 replication	994:1042	Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells	994:1073	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	7	54	theme	mammalian	1121:1129	arg1	cells					1131:1135	mammalian cells	1121:1135	mammalian cells	1121:1135	Neither inhibitor was significantly toxic to mammalian cells, nor showed in vitro cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	1	55	dep	Escherichia	115:125	arg1	coli					127:130	coli	127:130	coli	127:130	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	56	theme	glycosyltransferase	252:270	arg1	enzymes					272:278	glycosyltransferase enzymes	252:278	glycosyltransferase enzymes	252:278	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	56	theme	glycosyltransferase	252:270	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	3	57	theme	small	616:620	arg1	molecules					622:630	small molecules	616:630	small molecules that inhibit NleB/SseK activity	616:662	We conducted high-throughput screening assays to identify small molecules that inhibit NleB/SseK activity.
30619781	8	58	theme	potential	1336:1344	arg1	utility					1323:1329	utility	1323:1329	utility	1323:1329	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	8	58	theme	potential	1336:1344	arg1	strategy					1370:1377	a potential alternative therapeutic strategy	1334:1377	a potential alternative therapeutic strategy to antibiotics	1334:1392	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	1	59	theme	Salmonella	161:170	arg1	proteins					137:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins	72:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	59	theme	Salmonella	161:170	arg1	proteins					186:193	the Salmonella enterica SseK proteins	157:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	59	theme	Salmonella	161:170	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	8	60	theme	chemistry	1292:1300	arg1	refinements					1302:1312	medicinal chemistry refinements	1282:1312	medicinal chemistry refinements	1282:1312	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	8	61	theme	bacterial	1433:1441	arg1	glycosyltransferases					1443:1462	bacterial glycosyltransferases	1433:1462	bacterial glycosyltransferases	1433:1462	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	2	62	theme	arginines	425:433	arg1	groups					415:420	the guanidinium groups	399:420	the guanidinium groups of arginines, which are poor nucleophiles	399:462	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	2	62	theme	arginines	425:433	arg1	nucleophiles					451:462	poor nucleophiles	446:462	poor nucleophiles	446:462	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	2	62	theme	arginines	425:433	arg1	arginines					425:433	arginines	425:433	arginines	425:433	This modification is unusual because it occurs on the guanidinium groups of arginines, which are poor nucleophiles, and is distinct from the activity of the mammalian O-linked N-acetylglucosaminyltransferase.
30619781	6	63	dep	Salmonella	994:1003	arg1	enterica					1005:1012	enterica	1005:1012	enterica	1005:1012	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	8	64	theme	medicinal	1282:1290	arg1	chemistry					1292:1300	medicinal chemistry	1282:1300	medicinal chemistry refinements	1282:1312	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	6	65	theme	14028	1026:1030	arg1	replication					1032:1042	Salmonella enterica strain ATCC 14028 replication	994:1042	Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells	994:1073	These compounds were also capable of inhibiting Salmonella enterica strain ATCC 14028 replication in mouse macrophage-like cells.
30619781	8	66	theme	therapeutic	1358:1368	arg1	utility					1323:1329	utility	1323:1329	utility	1323:1329	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	8	66	theme	therapeutic	1358:1368	arg1	strategy					1370:1377	a potential alternative therapeutic strategy	1334:1377	a potential alternative therapeutic strategy to antibiotics	1334:1392	These compounds or derivatives generated from medicinal chemistry refinements may have utility as a potential alternative therapeutic strategy to antibiotics or as reagents to further the study of bacterial glycosyltransferases.
30619781	1	67	theme	SseK	181:184	arg1	proteins					137:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins	72:144	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	67	theme	SseK	181:184	arg1	proteins					186:193	the Salmonella enterica SseK proteins	157:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins	72:193	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30619781	1	67	theme	SseK	181:184	arg1	effectors					225:233	type III secretion system effectors	199:233	type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues	199:346	The enteropathogenic and enterohemorrhagic Escherichia coli NleB proteins as well as the Salmonella enterica SseK proteins are type III secretion system effectors that function as glycosyltransferase enzymes to post-translationally modify host substrates on arginine residues.
30517873	5	0	theme	phagophore	1037:1046	arg1	formation					1048:1056	phagophore formation	1037:1056	phagophore formation	1037:1056	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	3	1	dep	N-acetylglucosamine	500:518	arg1	O-GlcNAcylated					521:534	O-GlcNAcylated	521:534	O-GlcNAcylated	521:534	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	2	2	theme	activity	424:431	arg1	activation					405:414	the activation	401:414	the activation of ULK1 activity	401:431	Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity.
30517873	6	3	theme	therapeutic	1247:1257	arg1	intervention					1259:1270	potential therapeutic intervention	1237:1270	potential therapeutic intervention in autophagy-related diseases	1237:1300	Our findings provide insights into the crosstalk between dephosphorylation and O-GlcNAcylation during autophagy and specify a molecular framework for potential therapeutic intervention in autophagy-related diseases.
30517873	4	4	theme	ULK1	638:641	arg1	O-GlcNAcylation					643:657	ULK1 O-GlcNAcylation	638:657	ULK1 O-GlcNAcylation	638:657	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	6	5	theme	potential	1237:1245	arg1	intervention					1259:1270	potential therapeutic intervention	1237:1270	potential therapeutic intervention in autophagy-related diseases	1237:1300	Our findings provide insights into the crosstalk between dephosphorylation and O-GlcNAcylation during autophagy and specify a molecular framework for potential therapeutic intervention in autophagy-related diseases.
30517873	4	6	theme	757	747:749	arg1	site					751:754	the serine 757 site	736:754	the serine 757 site	736:754	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	3	7	from	attachment	477:486	arg1	site					558:561	the threonine 754 site	540:561	the threonine 754 site	540:561	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	1	8	from	initiation	257:266	arg1	response					284:291	response	284:291	response to starvation	284:305	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	4	9	theme	serine	740:745	arg1	site					751:754	the serine 757 site	736:754	the serine 757 site	736:754	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	1	10	theme	mechanistic	145:155	arg1	target					157:162	the mechanistic target	141:162	the mechanistic target of rapamycin (mTOR)	141:182	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	6	11	theme	molecular	1213:1221	arg1	framework					1223:1231	a molecular framework	1211:1231	a molecular framework for potential therapeutic intervention in autophagy-related diseases	1211:1300	Our findings provide insights into the crosstalk between dephosphorylation and O-GlcNAcylation during autophagy and specify a molecular framework for potential therapeutic intervention in autophagy-related diseases.
30517873	3	12	from	site	558:561	arg1	ULK1					465:468	ULK1	465:468	ULK1	465:468	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	3	12	from	site	558:561	arg1	attachment					477:486	the attachment	473:486	the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation	473:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	1	13	theme	target	157:162	arg1	Unc-51-like-kinase					93:110	Unc-51-like-kinase 1	93:112	Unc-51-like-kinase 1 (ULK1)	93:119	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	1	13	theme	target	157:162	arg1	target					126:131	a target	124:131	a target	124:131	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	0	14	theme	Autophagy	71:79	arg1	Initiation					81:90	Autophagy Initiation	71:90	Autophagy Initiation	71:90	ULK1 O-GlcNAcylation Is Crucial for Activating VPS34 via ATG14L during Autophagy Initiation.
30517873	3	15	theme	N-acetylglucosamine	500:518	arg1	ULK1					465:468	ULK1	465:468	ULK1	465:468	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	3	15	theme	N-acetylglucosamine	500:518	arg1	attachment					477:486	the attachment	473:486	the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation	473:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	0	16	theme	ULK1	0:3	arg1	O-GlcNAcylation					5:19	ULK1 O-GlcNAcylation	0:19	ULK1 O-GlcNAcylation	0:19	ULK1 O-GlcNAcylation Is Crucial for Activating VPS34 via ATG14L during Autophagy Initiation.
30517873	4	17	from	phosphorylation	717:731	arg1	site					751:754	the serine 757 site	736:754	the serine 757 site	736:754	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	4	18	theme	mTOR-dependent	702:715	arg1	phosphorylation					717:731	dephosphorylation of adjacent mTOR-dependent phosphorylation	672:731	dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1)	672:785	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	1	19	theme	rapamycin	167:175	arg1	kinase					210:215	AMP-activated protein kinase	188:215	AMP-activated protein kinase (AMPK)	188:222	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	1	19	theme	rapamycin	167:175	arg1	target					157:162	the mechanistic target	141:162	the mechanistic target of rapamycin (mTOR)	141:182	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	1	19	theme	rapamycin	167:175	arg1	AMPK					218:221	AMPK	218:221	AMPK	218:221	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	5	20	theme	phosphatidylinositol-	970:990	arg1	-phosphate					994:1003	phosphatidylinositol-(3)-phosphate	970:1003	phosphatidylinositol-(3)-phosphate (PI(3)P)	970:1012	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	5	20	theme	phosphatidylinositol-	970:990	arg1	P					1011:1011	PI(3)P	1006:1011	PI(3)P	1006:1011	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	5	21	theme	kinase	924:929	arg1	activation					904:913	the activation	900:913	the activation of lipid kinase VPS34	900:935	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	5	22	theme	lipid	918:922	arg1	kinase					924:929	lipid kinase VPS34	918:935	lipid kinase VPS34	918:935	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	3	23	theme	O-linked	491:498	arg1	N-acetylglucosamine					500:518	O-linked N-acetylglucosamine	491:518	O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation	491:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	2	24	theme	ULK1	419:422	arg1	activity					424:431	ULK1 activity	419:431	ULK1 activity	419:431	Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity.
30517873	2	25	theme	mTOR	349:352	arg1	dissociation					333:344	dissociation	333:344	dissociation of mTOR from ULK1 and phosphorylation by AMPK	333:390	Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity.
30517873	5	26	theme	autophagy	1076:1084	arg1	initiation					1062:1071	initiation	1062:1071	initiation of autophagy	1062:1084	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	5	26	theme	autophagy	1076:1084	arg1	formation					1048:1056	phagophore formation	1037:1056	phagophore formation	1037:1056	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	3	27	theme	O-linked	566:573	arg1	transferase					595:605	O-linked N-acetylglucosamine transferase	566:605	O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation	566:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	3	27	theme	O-linked	566:573	arg1	OGT					608:610	OGT	608:610	OGT	608:610	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	5	28	dep	P	1011:1011	arg1	3					1009:1009	3	1009:1009	3	1009:1009	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	4	29	from	phosphorylation	791:805	arg1	site					751:754	the serine 757 site	736:754	the serine 757 site	736:754	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	5	30	theme	ULK1	816:819	arg1	O-GlcNAcylation					821:835	ULK1 O-GlcNAcylation	816:835	ULK1 O-GlcNAcylation	816:835	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	3	31	theme	N-acetylglucosamine	575:593	arg1	transferase					595:605	O-linked N-acetylglucosamine transferase	566:605	O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation	566:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	3	31	theme	N-acetylglucosamine	575:593	arg1	OGT					608:610	OGT	608:610	OGT	608:610	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	5	32	theme	-phosphate	994:1003	arg1	production					956:965	the production	952:965	the production	952:965	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	6	33	from	intervention	1259:1270	arg1	diseases					1293:1300	autophagy-related diseases	1275:1300	autophagy-related diseases	1275:1300	Our findings provide insights into the crosstalk between dephosphorylation and O-GlcNAcylation during autophagy and specify a molecular framework for potential therapeutic intervention in autophagy-related diseases.
30517873	5	34	theme	PI	1006:1007	arg1	-phosphate					994:1003	phosphatidylinositol-(3)-phosphate	970:1003	phosphatidylinositol-(3)-phosphate (PI(3)P)	970:1012	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	5	34	theme	PI	1006:1007	arg1	P					1011:1011	PI(3)P	1006:1011	PI(3)P	1006:1011	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	1	35	theme	autophagy	271:279	arg1	initiation					257:266	the initiation	253:266	the initiation of autophagy in response to starvation	253:305	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	6	36	theme	autophagy-related	1275:1291	arg1	diseases					1293:1300	autophagy-related diseases	1275:1300	autophagy-related diseases	1275:1300	Our findings provide insights into the crosstalk between dephosphorylation and O-GlcNAcylation during autophagy and specify a molecular framework for potential therapeutic intervention in autophagy-related diseases.
30517873	3	37	theme	glucose	618:624	arg1	starvation					626:635	glucose starvation	618:635	glucose starvation	618:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	4	38	theme	adjacent	693:700	arg1	phosphorylation					717:731	dephosphorylation of adjacent mTOR-dependent phosphorylation	672:731	dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1)	672:785	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	5	39	dep	binding	852:858	arg1	of ATG14L					880:888	of ATG14L	880:888	of ATG14L	880:888	ULK1 O-GlcNAcylation is crucial for binding and phosphorylation of ATG14L, allowing the activation of lipid kinase VPS34 and leading to the production of phosphatidylinositol-(3)-phosphate (PI(3)P), which is required for phagophore formation and initiation of autophagy.
30517873	1	40	theme	AMP-activated	188:200	arg1	kinase					210:215	AMP-activated protein kinase	188:215	AMP-activated protein kinase (AMPK)	188:222	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	1	40	theme	AMP-activated	188:200	arg1	AMPK					218:221	AMPK	218:221	AMPK	218:221	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	4	41	theme	protein	759:765	arg1	phosphatase					767:777	protein phosphatase 1 	759:780	protein phosphatase 1 (PP1)	759:785	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	4	41	theme	protein	759:765	arg1	PP1					782:784	PP1	782:784	PP1	782:784	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	2	42	from	ULK1	359:362	arg1	dissociation					333:344	dissociation	333:344	dissociation of mTOR from ULK1 and phosphorylation by AMPK	333:390	Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity.
30517873	4	43	theme	dephosphorylation of	672:691	arg1	phosphorylation					717:731	dephosphorylation of adjacent mTOR-dependent phosphorylation	672:731	dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1)	672:785	ULK1 O-GlcNAcylation occurs after dephosphorylation of adjacent mTOR-dependent phosphorylation on the serine 757 site by protein phosphatase 1 (PP1) and phosphorylation by AMPK.
30517873	3	44	from	N-acetylglucosamine	500:518	arg1	site					558:561	the threonine 754 site	540:561	the threonine 754 site	540:561	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	1	45	theme	protein	202:208	arg1	kinase					210:215	AMP-activated protein kinase	188:215	AMP-activated protein kinase (AMPK)	188:222	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	1	45	theme	protein	202:208	arg1	AMPK					218:221	AMPK	218:221	AMPK	218:221	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	3	46	theme	threonine	544:552	arg1	site					558:561	the threonine 754 site	540:561	the threonine 754 site	540:561	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	1	47	theme	kinase	210:215	arg1	Unc-51-like-kinase					93:110	Unc-51-like-kinase 1	93:112	Unc-51-like-kinase 1 (ULK1)	93:119	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	1	47	theme	kinase	210:215	arg1	target					126:131	a target	124:131	a target	124:131	Unc-51-like-kinase 1 (ULK1) is a target of both the mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), whose role is to facilitate the initiation of autophagy in response to starvation.
30517873	3	48	link	O-linked	491:498	arg1	N-acetylglucosamine					500:518	O-linked N-acetylglucosamine	491:518	O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation	491:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	2	49	from	phosphorylation	368:382	arg1	dissociation					333:344	dissociation	333:344	dissociation of mTOR from ULK1 and phosphorylation by AMPK	333:390	Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity.
30517873	2	50	theme	glucose	313:319	arg1	starvation					321:330	glucose starvation	313:330	glucose starvation	313:330	Upon glucose starvation, dissociation of mTOR from ULK1 and phosphorylation by AMPK leads to the activation of ULK1 activity.
30517873	3	51	link	O-linked	566:573	arg1	transferase					595:605	O-linked N-acetylglucosamine transferase	566:605	O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation	566:635	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30517873	3	51	link	O-linked	566:573	arg1	OGT					608:610	OGT	608:610	OGT	608:610	Here, we provide evidence that ULK1 is the attachment of O-linked N-acetylglucosamine (O-GlcNAcylated) on the threonine 754 site by O-linked N-acetylglucosamine transferase (OGT) upon glucose starvation.
30181388	0	0	theme	Tyrosine	64:71	arg1	Kinases					73:79	Glioblastoma Receptor Tyrosine Kinases	42:79	Glioblastoma Receptor Tyrosine Kinases	42:79	No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases.
30181388	1	1	gly	glycosylation	147:159	arg1	kinases					211:217	multiple receptor tyrosine kinases	184:217	multiple receptor tyrosine kinases in glioblastoma (GBM)	184:239	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	2	from	glycosylation	147:159	arg1	glioblastoma					222:233	glioblastoma	222:233	glioblastoma (GBM)	222:239	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	2	from	glycosylation	147:159	arg1	GBM					236:238	GBM	236:238	GBM	236:238	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	3	link	N-linked	103:110	arg1	glycosylation					112:124	N-linked glycosylation	103:124	N-linked glycosylation	103:124	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	0	4	theme	Receptor	55:62	arg1	Kinases					73:79	Glioblastoma Receptor Tyrosine Kinases	42:79	Glioblastoma Receptor Tyrosine Kinases	42:79	No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases.
30181388	2	5	dep	Baro	420:423	arg1	al.					428:430	Baro et al.	420:430	Baro et al.	420:430	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	2	6	theme	GBM	278:280	arg1	models					268:273	multiple models	259:273	multiple models of GBM	259:280	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	2	7	theme	multiple	259:266	arg1	models					268:273	multiple models	259:273	multiple models of GBM	259:280	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	2	8	theme	related	401:407	arg1	article					409:415	active PTEN.See related article	385:415	active PTEN.See related article	385:415	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	2	9	theme	active	385:390	arg1	article					409:415	active PTEN.See related article	385:415	active PTEN.See related article	385:415	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	2	10	theme	PTEN.See	392:399	arg1	article					409:415	active PTEN.See related article	385:415	active PTEN.See related article	385:415	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	1	11	theme	novel	84:88	arg1	NGI-1					127:131	NGI-1	127:131	NGI-1	127:131	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	11	theme	novel	84:88	arg1	inhibitor					90:98	A novel inhibitor	82:98	A novel inhibitor of N-linked glycosylation (NGI-1)	82:132	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	12	theme	multiple	184:191	arg1	kinases					211:217	multiple receptor tyrosine kinases	184:217	multiple receptor tyrosine kinases in glioblastoma (GBM)	184:239	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	0	13	theme	New	18:20	arg1	Strategy					22:29	A New Strategy	16:29	A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases	16:79	No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases.
30181388	2	14	from	GBMs	368:371	arg1	effective					355:363	effective	355:363	effective	355:363	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	1	15	theme	receptor	193:200	arg1	kinases					211:217	multiple receptor tyrosine kinases	184:217	multiple receptor tyrosine kinases in glioblastoma (GBM)	184:239	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	0	16	dep	Strategy	22:29	arg1	Inhibit					34:40	Inhibit	34:40	to Inhibit Glioblastoma Receptor Tyrosine Kinases	31:79	No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases.
30181388	1	17	theme	tyrosine	202:209	arg1	kinases					211:217	multiple receptor tyrosine kinases	184:217	multiple receptor tyrosine kinases in glioblastoma (GBM)	184:239	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	18	from	glioblastoma	222:233	arg1	phosphorylation					165:179	phosphorylation	165:179	phosphorylation	165:179	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	18	from	glioblastoma	222:233	arg1	glycosylation					147:159	glycosylation	147:159	glycosylation	147:159	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	19	dep	glycosylation	147:159	arg1	the					143:145	the	143:145	the	143:145	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	20	from	kinases	211:217	arg1	glioblastoma					222:233	glioblastoma	222:233	glioblastoma (GBM)	222:239	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	20	from	kinases	211:217	arg1	GBM					236:238	GBM	236:238	GBM	236:238	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	2	21	from	effective	355:363	arg1	GBMs					368:371	GBMs	368:371	GBMs that retain active PTEN.See related article by Baro et al., p. 784	368:438	NGI-1 sensitizes multiple models of GBM to chemotherapy and radiation in vitro and in vivo and may be especially effective in GBMs that retain active PTEN.See related article by Baro et al., p. 784.
30181388	1	22	theme	N-linked	103:110	arg1	glycosylation					112:124	N-linked glycosylation	103:124	N-linked glycosylation	103:124	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	23	theme	kinases	211:217	arg1	phosphorylation					165:179	phosphorylation	165:179	phosphorylation	165:179	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	23	theme	kinases	211:217	arg1	glycosylation					147:159	glycosylation	147:159	glycosylation	147:159	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	24	theme	glycosylation	112:124	arg1	NGI-1					127:131	NGI-1	127:131	NGI-1	127:131	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	24	theme	glycosylation	112:124	arg1	inhibitor					90:98	A novel inhibitor	82:98	A novel inhibitor of N-linked glycosylation (NGI-1)	82:132	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	0	25	theme	Glioblastoma	42:53	arg1	Kinases					73:79	Glioblastoma Receptor Tyrosine Kinases	42:79	Glioblastoma Receptor Tyrosine Kinases	42:79	No Sugar Added: A New Strategy to Inhibit Glioblastoma Receptor Tyrosine Kinases.
30181388	1	26	from	phosphorylation	165:179	arg1	glioblastoma					222:233	glioblastoma	222:233	glioblastoma (GBM)	222:239	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30181388	1	26	from	phosphorylation	165:179	arg1	GBM					236:238	GBM	236:238	GBM	236:238	A novel inhibitor of N-linked glycosylation (NGI-1) inhibits the glycosylation and phosphorylation of multiple receptor tyrosine kinases in glioblastoma (GBM).
30763493	12	0	contain	had	1939:1941	arg1	products					1889:1896	The products	1885:1896	The products	1885:1896	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	0	contain	had	1939:1941	arg1	had					1939:1941	had	1939:1941	had a high score of essential amino acids due to the introduction of a combination of proteins	1939:2032	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	0	contain	had	1939:1941	arg2	score					1950:1954	a high score	1943:1954	a high score of essential amino acids	1943:1979	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	0	contain	had	1939:1941	arg1	balanced					1903:1910	balanced	1903:1910	balanced	1903:1910	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	9	1	from	absence	1300:1306	arg1	composition					1357:1367	the composition	1353:1367	the composition of the developed products	1353:1393	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	7	2	theme	foods	1093:1097	arg1	composition					1047:1057	composition	1047:1057	composition	1047:1057	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	7	2	theme	foods	1093:1097	arg1	technology					1063:1072	technology	1063:1072	technology	1063:1072	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	2	3	theme	DM	291:292	arg1	patients					294:301	DM patients	291:301	DM patients in the world in 2015	291:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	13	4	theme	dietary	2259:2265	arg1	fibers					2267:2272	soluble dietary fibers	2251:2272	soluble dietary fibers	2251:2272	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	13	4	theme	dietary	2259:2265	arg1	%					2248:2248	15%	2246:2248	15%	2246:2248	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	15	5	theme	low-calorie	2578:2588	arg1	diet					2590:2593	the low-calorie diet	2574:2593	the low-calorie diet	2574:2593	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	2	6	from	number	281:286	arg1	world					310:314	the world	306:314	the world in 2015	306:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	14	7	theme	polyphenols	2413:2423	arg1	content					2402:2408	The content	2398:2408	The content of polyphenols	2398:2423	The content of polyphenols was about a half of its adequate level of consumption.
30763493	6	8	from	use	911:913	arg1	therapy					922:928	the therapy	918:928	the therapy of patients with type 2 diabetes	918:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	13	9	theme	drink	2105:2109	arg1	form					2095:2098	the form	2091:2098	the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%	2091:2395	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	15	10	from	stabilization	2607:2619	arg1	patients					2661:2668	patients	2661:2668	patients with type 2 DM	2661:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	4	11	theme	adult	545:549	arg1	population					551:560	the adult population	541:560	the adult population	541:560	Russia ranks fifth among the ten countries with the largest number of the adult population with diabetes.
30763493	0	12	with	patients	96:103	arg1	diabetes					117:124	type 2 diabetes	110:124	type 2 diabetes	110:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	10	13	theme	low	1616:1618	arg1	humidity					1620:1627	low humidity	1616:1627	low humidity	1616:1627	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	1	14	theme	diabetes	162:169	arg1	DM					181:182	DM	181:182	DM	181:182	In recent years, the incidence of diabetes mellitus (DM) in the world is growing steadily.
30763493	1	14	theme	diabetes	162:169	arg1	mellitus					171:178	diabetes mellitus	162:178	diabetes mellitus (DM)	162:183	In recent years, the incidence of diabetes mellitus (DM) in the world is growing steadily.
30763493	6	15	theme	technology	836:845	arg1	development					805:815	the development	801:815	the development of composition and technology of specialized foods	801:866	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	6	15	theme	technology	836:845	arg1	assessment					872:881	assessment	872:881	assessment of the possibility of their use in the therapy of patients with type 2 diabetes	872:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	15	16	theme	diet	2590:2593	arg1	composition					2559:2569	the composition	2555:2569	the composition of the low-calorie diet	2555:2593	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	9	17	theme	digestible	1323:1332	arg1	polysaccharides					1334:1348	digestible polysaccharides	1323:1348	digestible polysaccharides	1323:1348	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	6	18	theme	composition	820:830	arg1	development					805:815	the development	801:815	the development of composition and technology of specialized foods	801:866	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	6	18	theme	composition	820:830	arg1	assessment					872:881	assessment	872:881	assessment of the possibility of their use in the therapy of patients with type 2 diabetes	872:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	5	19	with	patients	611:618	arg1	DM					632:633	type 2 DM	625:633	type 2 DM	625:633	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	4	20	theme	largest	523:529	arg1	number					531:536	the largest number	519:536	the largest number of the adult population	519:560	Russia ranks fifth among the ten countries with the largest number of the adult population with diabetes.
30763493	14	21	theme	adequate	2449:2456	arg1	level					2458:2462	its adequate level	2445:2462	its adequate level of consumption	2445:2477	The content of polyphenols was about a half of its adequate level of consumption.
30763493	13	22	theme	vitamins	2287:2294	arg1	groups					2296:2301	vitamins groups	2287:2301	vitamins groups B	2287:2303	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	5	23	theme	carbohydrate	704:715	arg1	profile					717:723	a modified carbohydrate profile	693:723	a modified carbohydrate profile containing ingredients with hypoglycemic action	693:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	15	24	theme	specialized	2497:2507	arg1	foods					2509:2513	specialized foods	2497:2513	specialized foods with a modified carbohydrate profile	2497:2550	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	13	25	theme	acids	2217:2221	arg1	ω-3					2223:2225	polyunsaturated fatty acids ω-3	2195:2225	polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%	2195:2315	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	13	25	theme	acids	2217:2221	arg1	%					2192:2192	15-22%	2187:2192	15-22%	2187:2192	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	11	26	dep	mOsm/kg	1838:1844	arg1	characterized					1853:1865	characterized	1853:1865	characterized them as isotonic	1853:1882	The osmolality of the beverages restored in accordance with the method of preparation was 310 and 258 mOsm/kg, which characterized them as isotonic.
30763493	15	27	theme	glucose	2643:2649	arg1	levels					2651:2656	postprandial blood glucose levels	2624:2656	postprandial blood glucose levels in patients with type 2 DM	2624:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	4	28	theme	population	551:560	arg1	number					531:536	the largest number	519:536	the largest number of the adult population	519:560	Russia ranks fifth among the ten countries with the largest number of the adult population with diabetes.
30763493	12	29	theme	acid	1921:1924	arg1	composition					1926:1936	amino acid composition	1915:1936	amino acid composition	1915:1936	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	13	30	theme	product	2080:2086	arg1	g					2070:2070	30 g	2067:2070	30 g	2067:2070	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	6	31	theme	possibility	890:900	arg1	development					805:815	the development	801:815	the development of composition and technology of specialized foods	801:866	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	6	31	theme	possibility	890:900	arg1	assessment					872:881	assessment	872:881	assessment of the possibility of their use in the therapy of patients with type 2 diabetes	872:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	8	32	from	distribution	1221:1232	arg1	mass					1275:1278	the mass	1271:1278	the mass of the product	1271:1293	The technology of step-bystep mixing contributed to the uniform distribution of biologically active substances in the mass of the product.
30763493	9	33	dep	%	1435:1435	arg1	1					1434:1434	1	1434:1434	1	1434:1434	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	7	34	theme	specialized	1081:1091	arg1	foods					1093:1097	two specialized foods	1077:1097	two specialized foods	1077:1097	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	13	35	theme	groups	2296:2301	arg1	B					2303:2303	vitamins groups B	2287:2303	vitamins groups B	2287:2303	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	13	35	theme	groups	2296:2301	arg1	%					2234:2234	10%	2232:2234	10%	2232:2234	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	9	36	theme	products	1386:1393	arg1	composition					1357:1367	the composition	1353:1367	the composition of the developed products	1353:1393	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	8	37	theme	mixing	1187:1192	arg1	technology					1161:1170	The technology	1157:1170	The technology of step-bystep mixing	1157:1192	The technology of step-bystep mixing contributed to the uniform distribution of biologically active substances in the mass of the product.
30763493	13	38	from	g	2070:2070	arg1	form					2095:2098	the form	2091:2098	the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%	2091:2395	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	10	39	with	products	1602:1609	arg1	humidity					1620:1627	low humidity	1616:1627	low humidity	1616:1627	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	12	40	dep	balanced	1903:1910	arg1	had					1939:1941	had	1939:1941	had a high score of essential amino acids due to the introduction of a combination of proteins	1939:2032	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	40	dep	balanced	1903:1910	arg1	products					1889:1896	The products	1885:1896	The products	1885:1896	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	40	dep	balanced	1903:1910	arg1	balanced					1903:1910	balanced	1903:1910	balanced	1903:1910	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	15	41	with	foods	2509:2513	arg1	profile					2544:2550	a modified carbohydrate profile	2520:2550	a modified carbohydrate profile	2520:2550	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	6	42	theme	specialized	850:860	arg1	foods					862:866	specialized foods	850:866	specialized foods	850:866	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	8	43	theme	uniform	1213:1219	arg1	distribution					1221:1232	the uniform distribution	1209:1232	the uniform distribution of biologically active substances in the mass of the product	1209:1293	The technology of step-bystep mixing contributed to the uniform distribution of biologically active substances in the mass of the product.
30763493	15	44	with	patients	2661:2668	arg1	DM					2682:2683	type 2 DM	2675:2683	type 2 DM	2675:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	13	45	theme	polyunsaturated	2195:2209	arg1	acids					2217:2221	polyunsaturated fatty acids	2195:2221	polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%	2195:2315	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	9	46	from	content	1460:1466	arg1	component					1483:1491	the protein component	1471:1491	the protein component	1471:1491	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	6	47	theme	patients	933:940	arg1	therapy					922:928	the therapy	918:928	the therapy of patients with type 2 diabetes	918:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	0	48	theme	[Specialized	0:11	arg1	products					18:25	[Specialized food products	0:25	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes	0:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	13	49	theme	trace	2369:2373	arg1	elements					2375:2382	trace elements	2369:2382	trace elements	2369:2382	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	13	49	theme	trace	2369:2373	arg1	%					2353:2353	17-46%	2348:2353	17-46%	2348:2353	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	13	50	theme	amino	2172:2176	arg1	acids					2178:2182	essential amino acids	2162:2182	essential amino acids	2162:2182	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	8	51	theme	active	1250:1255	arg1	substances					1257:1266	biologically active substances	1237:1266	biologically active substances	1237:1266	The technology of step-bystep mixing contributed to the uniform distribution of biologically active substances in the mass of the product.
30763493	10	52	theme	standard	1521:1528	arg1	values					1530:1535	the standard values	1517:1535	the standard values for similar products	1517:1556	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	5	53	theme	foods	682:686	arg1	inclusion					657:665	the inclusion	653:665	the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action	653:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	9	54	theme	lactose	1437:1443	arg1	presence					1416:1423	the presence	1412:1423	the presence of about 1% lactose was due to its content in the protein component	1412:1491	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	5	55	theme	hypoglycemic	753:764	arg1	action					766:771	hypoglycemic action	753:771	hypoglycemic action	753:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	0	56	theme	dietary	66:72	arg1	correction					74:83	dietary correction	66:83	dietary correction of diet of patients with type 2 diabetes	66:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	15	57	theme	modified	2522:2529	arg1	profile					2544:2550	a modified carbohydrate profile	2520:2550	a modified carbohydrate profile	2520:2550	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	11	58	theme	beverages	1758:1766	arg1	osmolality					1740:1749	The osmolality	1736:1749	The osmolality of the beverages restored in accordance with the method of preparation	1736:1820	The osmolality of the beverages restored in accordance with the method of preparation was 310 and 258 mOsm/kg, which characterized them as isotonic.
30763493	11	58	theme	beverages	1758:1766	arg1	mOsm/kg					1838:1844	310 and 258 mOsm/kg	1826:1844	310 and 258 mOsm/kg	1826:1844	The osmolality of the beverages restored in accordance with the method of preparation was 310 and 258 mOsm/kg, which characterized them as isotonic.
30763493	7	59	theme	diet	1013:1016	arg1	therapy					1018:1024	diet therapy	1013:1024	diet therapy	1013:1024	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	0	60	theme	modified	32:39	arg1	profile					54:60	modified carbohydrate profile	32:60	modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes	32:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	13	61	theme	daily	2140:2144	arg1	requirement					2146:2156	an average daily requirement	2129:2156	an average daily requirement for essential amino acids	2129:2182	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	15	62	theme	carbohydrate	2531:2542	arg1	profile					2544:2550	a modified carbohydrate profile	2520:2550	a modified carbohydrate profile	2520:2550	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	5	63	with	ingredients	736:746	arg1	action					766:771	hypoglycemic action	753:771	hypoglycemic action	753:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	10	64	theme	stability	1684:1692	arg1	prediction					1650:1659	the prediction	1646:1659	the prediction of the microbiological stability of the developed products	1646:1718	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	0	65	with	products	18:25	arg1	profile					54:60	modified carbohydrate profile	32:60	modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes	32:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	15	66	theme	postprandial	2624:2635	arg1	levels					2651:2656	postprandial blood glucose levels	2624:2656	postprandial blood glucose levels in patients with type 2 DM	2624:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	12	67	theme	acids	1975:1979	arg1	score					1950:1954	a high score	1943:1954	a high score of essential amino acids	1943:1979	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	7	68	theme	beverage	1114:1121	arg1	concentrates					1123:1134	beverage concentrates	1114:1134	beverage concentrates	1114:1134	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	10	69	theme	products	1711:1718	arg1	stability					1684:1692	the microbiological stability	1664:1692	the microbiological stability of the developed products	1664:1718	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	10	70	theme	water	1570:1574	arg1	typical					1590:1596	typical	1590:1596	typical	1590:1596	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	10	70	theme	water	1570:1574	arg1	activity					1576:1583	the values water activity	1559:1583	the values water activity	1559:1583	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	6	71	theme	study	793:797	arg1	purpose					778:784	The purpose	774:784	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.	774:962	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	9	72	theme	protein	1475:1481	arg1	component					1483:1491	the protein component	1471:1491	the protein component	1471:1491	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	2	73	theme	patients	294:301	arg1	number					281:286	the number	277:286	the number of DM patients in the world in 2015	277:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	2	73	theme	patients	294:301	arg1	million					332:338	415 million	328:338	415 million	328:338	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	6	74	theme	type	947:950	arg1	diabetes					954:961	type 2 diabetes	947:961	type 2 diabetes	947:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	6	75	dep	purpose	778:784	arg1	development					805:815	the development	801:815	the development of composition and technology of specialized foods	801:866	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	6	75	dep	purpose	778:784	arg1	assessment					872:881	assessment	872:881	assessment of the possibility of their use in the therapy of patients with type 2 diabetes	872:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	13	76	theme	soluble	2251:2257	arg1	fibers					2267:2272	soluble dietary fibers	2251:2272	soluble dietary fibers	2251:2272	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	13	76	theme	soluble	2251:2257	arg1	%					2248:2248	15%	2246:2248	15%	2246:2248	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	6	77	from	therapy	922:928	arg1	possibility					890:900	the possibility	886:900	the possibility of their use in the therapy of patients with type 2 diabetes	886:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	2	78	with	patients	365:372	arg1	diabetes					386:393	type 2 diabetes	379:393	type 2 diabetes	379:393	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	4	79	theme	Russia	471:476	arg1	ranks					478:482	Russia ranks	471:482	Russia ranks	471:482	Russia ranks fifth among the ten countries with the largest number of the adult population with diabetes.
30763493	12	80	theme	essential	1959:1967	arg1	acids					1975:1979	essential amino acids	1959:1979	essential amino acids	1959:1979	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	2	81	from	patients	294:301	arg1	world					310:314	the world	306:314	the world in 2015	306:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	12	82	theme	high	1945:1948	arg1	score					1950:1954	a high score	1943:1954	a high score of essential amino acids	1943:1979	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	13	83	from	product	2080:2086	arg1	form					2095:2098	the form	2091:2098	the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%	2091:2395	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	15	84	theme	type	2675:2678	arg1	DM					2682:2683	type 2 DM	2675:2683	type 2 DM	2675:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	5	85	with	foods	682:686	arg1	profile					717:723	a modified carbohydrate profile	693:723	a modified carbohydrate profile containing ingredients with hypoglycemic action	693:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	5	86	theme	Dietary	577:583	arg1	correction					585:594	Dietary correction	577:594	Dietary correction of the diet of patients with type 2 DM	577:633	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	1	87	theme	mellitus	171:178	arg1	incidence					149:157	the incidence	145:157	the incidence of diabetes mellitus (DM) in the world	145:196	In recent years, the incidence of diabetes mellitus (DM) in the world is growing steadily.
30763493	14	88	theme	level	2458:2462	arg1	half					2437:2440	a half	2435:2440	a half of its adequate level of consumption	2435:2477	The content of polyphenols was about a half of its adequate level of consumption.
30763493	9	89	theme	sucrose	1311:1317	arg1	absence					1300:1306	The absence	1296:1306	The absence of sucrose and digestible polysaccharides in the composition of the developed products	1296:1393	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	5	90	theme	modified	695:702	arg1	profile					717:723	a modified carbohydrate profile	693:723	a modified carbohydrate profile containing ingredients with hypoglycemic action	693:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	15	91	theme	levels	2651:2656	arg1	stabilization					2607:2619	the stabilization	2603:2619	the stabilization of postprandial blood glucose levels in patients with type 2 DM	2603:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	7	92	from	composition	1047:1057	arg1	form					1106:1109	the form	1102:1109	the form of beverage concentrates	1102:1134	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	5	93	theme	diet	603:606	arg1	correction					585:594	Dietary correction	577:594	Dietary correction of the diet of patients with type 2 DM	577:633	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	13	94	theme	fatty	2211:2215	arg1	acids					2217:2221	polyunsaturated fatty acids	2195:2221	polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%	2195:2315	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	15	95	theme	blood	2637:2641	arg1	levels					2651:2656	postprandial blood glucose levels	2624:2656	postprandial blood glucose levels in patients with type 2 DM	2624:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	14	96	theme	consumption	2467:2477	arg1	level					2458:2462	its adequate level	2445:2462	its adequate level of consumption	2445:2477	The content of polyphenols was about a half of its adequate level of consumption.
30763493	7	97	from	technology	1063:1072	arg1	form					1106:1109	the form	1102:1109	the form of beverage concentrates	1102:1134	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	15	98	theme	foods	2509:2513	arg1	inclusion					2484:2492	The inclusion	2480:2492	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet	2480:2593	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	10	99	theme	microbiological	1668:1682	arg1	stability					1684:1692	the microbiological stability	1664:1692	the microbiological stability of the developed products	1664:1718	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	12	100	from	balanced	1903:1910	arg1	composition					1926:1936	amino acid composition	1915:1936	amino acid composition	1915:1936	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	101	theme	amino	1915:1919	arg1	composition					1926:1936	amino acid composition	1915:1936	amino acid composition	1915:1936	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	5	102	theme	type	625:628	arg1	DM					632:633	type 2 DM	625:633	type 2 DM	625:633	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	11	103	theme	preparation	1810:1820	arg1	method					1800:1805	the method	1796:1805	the method of preparation	1796:1820	The osmolality of the beverages restored in accordance with the method of preparation was 310 and 258 mOsm/kg, which characterized them as isotonic.
30763493	9	104	theme	developed	1376:1384	arg1	products					1386:1393	the developed products	1372:1393	the developed products	1372:1393	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	9	105	dep	lactose	1437:1443	arg1	%					1435:1435	%	1435:1435	%	1435:1435	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	0	106	theme	diet	88:91	arg1	correction					74:83	dietary correction	66:83	dietary correction of diet of patients with type 2 diabetes	66:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	1	107	from	incidence	149:157	arg1	world					192:196	the world	188:196	the world	188:196	In recent years, the incidence of diabetes mellitus (DM) in the world is growing steadily.
30763493	2	108	theme	type	379:382	arg1	diabetes					386:393	type 2 diabetes	379:393	type 2 diabetes	379:393	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	8	109	theme	step-bystep	1175:1185	arg1	mixing					1187:1192	step-bystep mixing	1175:1192	step-bystep mixing	1175:1192	The technology of step-bystep mixing contributed to the uniform distribution of biologically active substances in the mass of the product.
30763493	0	110	theme	patients	96:103	arg1	correction					74:83	dietary correction	66:83	dietary correction of diet of patients with type 2 diabetes	66:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	15	111	from	levels	2651:2656	arg1	patients					2661:2668	patients	2661:2668	patients with type 2 DM	2661:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	6	112	theme	foods	862:866	arg1	technology					836:845	technology	836:845	technology	836:845	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	6	112	theme	foods	862:866	arg1	composition					820:830	composition	820:830	composition	820:830	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	6	113	from	possibility	890:900	arg1	therapy					922:928	the therapy	918:928	the therapy of patients with type 2 diabetes	918:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	5	114	contain	containing	725:734	arg2	ingredients					736:746	ingredients	736:746	ingredients with hypoglycemic action	736:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	5	114	contain	containing	725:734	arg1	profile					717:723	a modified carbohydrate profile	693:723	a modified carbohydrate profile containing ingredients with hypoglycemic action	693:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	0	115	theme	type	110:113	arg1	diabetes					117:124	type 2 diabetes	110:124	type 2 diabetes	110:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	15	116	from	patients	2661:2668	arg1	stabilization					2607:2619	the stabilization	2603:2619	the stabilization of postprandial blood glucose levels in patients with type 2 DM	2603:2683	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	5	117	theme	patients	611:618	arg1	diet					603:606	the diet	599:606	the diet of patients with type 2 DM	599:633	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	0	118	theme	food	13:16	arg1	products					18:25	[Specialized food products	0:25	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes	0:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	13	119	theme	essential	2162:2170	arg1	acids					2178:2182	essential amino acids	2162:2182	essential amino acids	2162:2182	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	4	120	with	countries	504:512	arg1	diabetes					567:574	diabetes	567:574	diabetes	567:574	Russia ranks fifth among the ten countries with the largest number of the adult population with diabetes.
30763493	4	120	with	countries	504:512	arg1	number					531:536	the largest number	519:536	the largest number of the adult population	519:560	Russia ranks fifth among the ten countries with the largest number of the adult population with diabetes.
30763493	12	121	theme	combination	2010:2020	arg1	introduction					1992:2003	the introduction	1988:2003	the introduction of a combination of proteins	1988:2032	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	5	122	theme	specialized	670:680	arg1	foods					682:686	specialized foods	670:686	specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action	670:771	Dietary correction of the diet of patients with type 2 DM is carried out by the inclusion of specialized foods with a modified carbohydrate profile containing ingredients with hypoglycemic action.
30763493	12	123	from	composition	1926:1936	arg1	products					1889:1896	The products	1885:1896	The products	1885:1896	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	123	from	composition	1926:1936	arg1	had					1939:1941	had	1939:1941	had a high score of essential amino acids due to the introduction of a combination of proteins	1939:2032	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	12	123	from	composition	1926:1936	arg1	balanced					1903:1910	balanced	1903:1910	balanced	1903:1910	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	2	124	theme	them	344:347	arg1	number					281:286	the number	277:286	the number of DM patients in the world in 2015	277:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	2	124	theme	them	344:347	arg1	million					332:338	415 million	328:338	415 million	328:338	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	10	125	theme	developed	1701:1709	arg1	products					1711:1718	the developed products	1697:1718	the developed products	1697:1718	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	12	126	theme	proteins	2025:2032	arg1	combination					2010:2020	a combination	2008:2020	a combination of proteins	2008:2032	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	0	127	theme	carbohydrate	41:52	arg1	profile					54:60	modified carbohydrate profile	32:60	modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes	32:124	[Specialized food products with modified carbohydrate profile for dietary correction of diet of patients with type 2 diabetes].
30763493	13	128	theme	one	2054:2056	arg1	consumption					2039:2049	The consumption	2035:2049	The consumption of one	2035:2056	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	9	129	theme	polysaccharides	1334:1348	arg1	absence					1300:1306	The absence	1296:1306	The absence of sucrose and digestible polysaccharides in the composition of the developed products	1296:1393	The absence of sucrose and digestible polysaccharides in the composition of the developed products was established, the presence of about 1% lactose was due to its content in the protein component.
30763493	13	130	theme	average	2132:2138	arg1	requirement					2146:2156	an average daily requirement	2129:2156	an average daily requirement for essential amino acids	2129:2182	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	6	131	theme	use	911:913	arg1	possibility					890:900	the possibility	886:900	the possibility of their use in the therapy of patients with type 2 diabetes	886:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	2	132	theme	patients	365:372	arg1	number					281:286	the number	277:286	the number of DM patients in the world in 2015	277:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	2	132	theme	patients	365:372	arg1	million					332:338	415 million	328:338	415 million	328:338	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	8	133	theme	substances	1257:1266	arg1	distribution					1221:1232	the uniform distribution	1209:1232	the uniform distribution of biologically active substances in the mass of the product	1209:1293	The technology of step-bystep mixing contributed to the uniform distribution of biologically active substances in the mass of the product.
30763493	13	134	from	form	2095:2098	arg1	g					2070:2070	30 g	2067:2070	30 g	2067:2070	The consumption of one serving (30 g) of the product in the form of a drink (200 ml) provided an average daily requirement for essential amino acids by 15-22%, polyunsaturated fatty acids ω-3 - by 10%, ω-6 - by 15%, soluble dietary fibers - by 50-55%, vitamins groups B - by 14-81%, C - by 46%, A, D3, E, K1 - by 17-46%, minerals and trace elements - by 10- 33%.
30763493	7	135	theme	medical	988:994	arg1	requirements					996:1007	the medical requirements	984:1007	the medical requirements for diet therapy for type 2 diabetes	984:1044	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	6	136	with	patients	933:940	arg1	diabetes					954:961	type 2 diabetes	947:961	type 2 diabetes	947:961	The purpose of the study - the development of composition and technology of specialized foods and assessment of the possibility of their use in the therapy of patients with type 2 diabetes.
30763493	2	137	from	world	310:314	arg1	number					281:286	the number	277:286	the number of DM patients in the world in 2015	277:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	2	137	from	world	310:314	arg1	2015					319:322	2015	319:322	2015	319:322	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	2	137	from	world	310:314	arg1	million					332:338	415 million	328:338	415 million	328:338	According to the international diabetes Federation (IDF), the number of DM patients in the world in 2015 was 415 million, of them more than 90% - patients with type 2 diabetes.
30763493	7	138	theme	concentrates	1123:1134	arg1	form					1106:1109	the form	1102:1109	the form of beverage concentrates	1102:1134	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
30763493	1	139	theme	recent	131:136	arg1	years					138:142	recent years	131:142	recent years	131:142	In recent years, the incidence of diabetes mellitus (DM) in the world is growing steadily.
30763493	10	140	theme	similar	1541:1547	arg1	products					1549:1556	similar products	1541:1556	similar products	1541:1556	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	12	141	theme	amino	1969:1973	arg1	acids					1975:1979	essential amino acids	1959:1979	essential amino acids	1959:1979	The products were balanced in amino acid composition, had a high score of essential amino acids due to the introduction of a combination of proteins.
30763493	10	142	theme	values	1563:1568	arg1	typical					1590:1596	typical	1590:1596	typical	1590:1596	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	10	142	theme	values	1563:1568	arg1	activity					1576:1583	the values water activity	1559:1583	the values water activity	1559:1583	Humidity didn't exceed the standard values for similar products, the values water activity were typical for products with low humidity, which justified the prediction of the microbiological stability of the developed products during storage.
30763493	15	143	from	inclusion	2484:2492	arg1	composition					2559:2569	the composition	2555:2569	the composition of the low-calorie diet	2555:2593	The inclusion of specialized foods with a modified carbohydrate profile in the composition of the low-calorie diet lead to the stabilization of postprandial blood glucose levels in patients with type 2 DM.
30763493	8	144	theme	product	1287:1293	arg1	mass					1275:1278	the mass	1271:1278	the mass of the product	1271:1293	The technology of step-bystep mixing contributed to the uniform distribution of biologically active substances in the mass of the product.
30763493	7	145	theme	type	1030:1033	arg1	diabetes					1037:1044	type 2 diabetes	1030:1044	type 2 diabetes	1030:1044	Taking into account the medical requirements for diet therapy for type 2 diabetes, composition and technology of two specialized foods in the form of beverage concentrates have been developed.
31333671	0	0	contain	Carry	45:49	arg1	Repertoires					15:25	Peripheral IgE Repertoires	0:25	Peripheral IgE Repertoires of Healthy Donors	0:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	0	0	contain	Carry	45:49	arg1	Donors					38:43	Healthy Donors	30:43	Healthy Donors	30:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	0	0	contain	Carry	45:49	arg2	Loads					69:73	Moderate Mutation Loads	51:73	Moderate Mutation Loads	51:73	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	7	1	theme	IgE	879:881	arg1	sequences					883:891	IgE sequences	879:891	IgE sequences	879:891	IgE sequences carried more somatic mutations than IgM, yet fewer than IgG and IgA.
31333671	8	2	theme	Many	962:965	arg1	sequences					971:979	Many IgE sequences	962:979	Many IgE sequences	962:979	Many IgE sequences contained N-linked glycosylation motifs.
31333671	5	3	theme	gene	671:674	arg1	usage					676:680	IGHV gene usage	666:680	IGHV gene usage	666:680	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	3	theme	gene	671:674	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	10	4	theme	immune	1209:1214	arg1	reactions					1216:1224	immune reactions	1209:1224	immune reactions that give rise to IgG or IgA	1209:1253	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	8	5	theme	N-linked	991:998	arg1	motifs					1014:1019	N-linked glycosylation motifs	991:1019	N-linked glycosylation motifs	991:1019	Many IgE sequences contained N-linked glycosylation motifs.
31333671	13	6	theme	desensitization	1793:1807	arg1	strategies					1809:1818	improved desensitization strategies	1784:1818	improved desensitization strategies	1784:1818	This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
31333671	5	7	theme	somatic	643:649	arg1	hypermutation					651:663	somatic hypermutation	643:663	somatic hypermutation	643:663	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	12	8	theme	cell	1612:1615	arg1	degranulation					1617:1629	mast cell degranulation	1607:1629	mast cell degranulation induced by allergen-specific, high-affinity IgE	1607:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	6	9	theme	certain	828:834	arg1	genes					841:845	certain IGHV genes	828:845	certain IGHV genes	828:845	IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes.
31333671	5	10	theme	selection	705:713	arg1	motifs					743:748	N-linked glycosylation motifs	720:748	N-linked glycosylation motifs	720:748	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	10	theme	selection	705:713	arg1	evidence					683:690	evidence	683:690	evidence of antigenic selection	683:713	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	10	theme	selection	705:713	arg1	usage					676:680	IGHV gene usage	666:680	IGHV gene usage	666:680	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	10	theme	selection	705:713	arg1	degree					633:638	degree	633:638	degree of somatic hypermutation	633:663	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	10	theme	selection	705:713	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	2	11	theme	healthy	305:311	arg1	repertoire					317:326	the healthy IgE repertoire	301:326	the healthy IgE repertoire	301:326	Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire.
31333671	11	12	dep	antigenic	1390:1398	arg1	drive					1400:1404	drive	1400:1404	drive	1400:1404	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	8	13	gly	glycosylation	1000:1012	arg2	motifs					1014:1019	N-linked glycosylation motifs	991:1019	N-linked glycosylation motifs	991:1019	Many IgE sequences contained N-linked glycosylation motifs.
31333671	12	14	theme	competitive	1576:1586	arg1	protection					1588:1597	competitive protection	1576:1597	competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE	1576:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	6	15	with	oligoclonal	789:799	arg1	usage					819:823	preferential usage	806:823	preferential usage of certain IGHV genes compared to the other isotypes	806:876	IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes.
31333671	2	16	theme	IgE	230:232	arg1	sequences					234:242	IgE sequences	230:242	IgE sequences	230:242	Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire.
31333671	11	17	with	affinity	1432:1439	arg1	evidence					1378:1385	little evidence	1371:1385	little evidence of antigenic drive	1371:1404	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	2	18	theme	little	266:271	arg1	information					273:283	little information	266:283	little information	266:283	Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire.
31333671	1	19	theme	allergic	128:135	arg1	disease					137:143	IgE-mediated allergic disease	115:143	IgE-mediated allergic disease	115:143	IgE-mediated allergic disease represents an increasing health problem.
31333671	3	20	theme	IgG	334:336	arg1	transcripts					352:362	IgM, IgG, IgA, and IgE transcripts	329:362	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals	329:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	0	21	theme	Mutation	60:67	arg1	Loads					69:73	Moderate Mutation Loads	51:73	Moderate Mutation Loads	51:73	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	3	22	theme	IgM	329:331	arg1	transcripts					352:362	IgM, IgG, IgA, and IgE transcripts	329:362	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals	329:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	11	23	theme	normal	1281:1286	arg1	IgE					1288:1290	normal IgE	1281:1290	normal IgE	1281:1290	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	1	24	theme	increasing	159:168	arg1	problem					177:183	an increasing health problem	156:183	an increasing health problem	156:183	IgE-mediated allergic disease represents an increasing health problem.
31333671	12	25	theme	healthy	1525:1531	arg1	repertoire					1537:1546	the healthy IgE repertoire	1521:1546	the healthy IgE repertoire	1521:1546	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	4	26	theme	Complete	504:511	arg1	regions					517:523	Complete VDJ regions	504:523	Complete VDJ regions	504:523	Complete VDJ regions were sequenced to near-exhaustion on the PacBio platform.
31333671	5	27	theme	glycosylation	729:741	arg1	motifs					743:748	N-linked glycosylation motifs	720:748	N-linked glycosylation motifs	720:748	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	27	theme	glycosylation	729:741	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	10	28	theme	healthy	1110:1116	arg1	individuals					1118:1128	healthy individuals	1110:1128	healthy individuals	1110:1128	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	5	29	theme	clonal	611:616	arg1	evidence					683:690	evidence	683:690	evidence of antigenic selection	683:713	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	29	theme	clonal	611:616	arg1	motifs					743:748	N-linked glycosylation motifs	720:748	N-linked glycosylation motifs	720:748	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	29	theme	clonal	611:616	arg1	usage					676:680	IGHV gene usage	666:680	IGHV gene usage	666:680	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	29	theme	clonal	611:616	arg1	degree					633:638	degree	633:638	degree of somatic hypermutation	633:663	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	29	theme	clonal	611:616	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	12	30	theme	repertoire	1537:1546	arg1	function					1509:1516	a primary function	1499:1516	a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE	1499:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	3	31	theme	IgA	339:341	arg1	transcripts					352:362	IgM, IgG, IgA, and IgE transcripts	329:362	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals	329:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	11	32	theme	specific	1445:1452	arg1	antigens					1454:1461	specific antigens	1445:1461	specific antigens	1445:1461	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	0	33	theme	Donors	38:43	arg1	Repertoires					15:25	Peripheral IgE Repertoires	0:25	Peripheral IgE Repertoires of Healthy Donors	0:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	0	33	theme	Donors	38:43	arg1	Donors					38:43	Healthy Donors	30:43	Healthy Donors	30:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	3	34	theme	peripheral	369:378	arg1	cells					388:392	peripheral blood B cells	369:392	peripheral blood B cells of five healthy, non-atopic individuals	369:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	5	35	gly	glycosylation	729:741	arg2	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	35	gly	glycosylation	729:741	arg2	motifs					743:748	N-linked glycosylation motifs	720:748	N-linked glycosylation motifs	720:748	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	3	36	theme	healthy	402:408	arg1	individuals					422:432	five healthy, non-atopic individuals	397:432	five healthy, non-atopic individuals	397:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	0	37	theme	Peripheral	0:9	arg1	Repertoires					15:25	Peripheral IgE Repertoires	0:25	Peripheral IgE Repertoires of Healthy Donors	0:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	0	37	theme	Peripheral	0:9	arg1	Donors					38:43	Healthy Donors	30:43	Healthy Donors	30:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	13	38	theme	background	1685:1694	arg1	knowledge					1696:1704	This background knowledge	1680:1704	This background knowledge	1680:1704	This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
31333671	0	39	theme	Healthy	30:36	arg1	Donors					38:43	Healthy Donors	30:43	Healthy Donors	30:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	6	40	theme	other	863:867	arg1	isotypes					869:876	the other isotypes	859:876	the other isotypes	859:876	IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes.
31333671	3	41	theme	B	386:386	arg1	cells					388:392	peripheral blood B cells	369:392	peripheral blood B cells of five healthy, non-atopic individuals	369:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	8	42	link	N-linked	991:998	arg1	motifs					1014:1019	N-linked glycosylation motifs	991:1019	N-linked glycosylation motifs	991:1019	Many IgE sequences contained N-linked glycosylation motifs.
31333671	10	43	theme	few	1157:1159	arg1	expansions					1168:1177	relatively few clonal expansions	1146:1177	relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA	1146:1253	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	6	44	theme	IgE	751:753	arg1	repertoires					755:765	IgE repertoires	751:765	IgE repertoires	751:765	IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes.
31333671	6	45	theme	genes	841:845	arg1	usage					819:823	preferential usage	806:823	preferential usage of certain IGHV genes compared to the other isotypes	806:876	IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes.
31333671	11	46	theme	antigenic	1390:1398	arg1	evidence					1378:1385	little evidence	1371:1385	little evidence of antigenic drive	1371:1404	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	2	47	theme	numerous	195:202	arg1	studies					204:210	numerous studies	195:210	numerous studies	195:210	Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire.
31333671	10	48	theme	apparent	1187:1194	arg1	relations					1196:1204	apparent relations	1187:1204	apparent relations to immune reactions that give rise to IgG or IgA	1187:1253	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	3	49	dep	unbiased	452:459	arg1	isotype-specific					482:497	isotype-specific	482:497	isotype-specific	482:497	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	3	49	dep	unbiased	452:459	arg1	template-switching					462:479	template-switching	462:479	template-switching	462:479	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	5	50	theme	hypermutation	651:663	arg1	motifs					743:748	N-linked glycosylation motifs	720:748	N-linked glycosylation motifs	720:748	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	50	theme	hypermutation	651:663	arg1	evidence					683:690	evidence	683:690	evidence of antigenic selection	683:713	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	50	theme	hypermutation	651:663	arg1	usage					676:680	IGHV gene usage	666:680	IGHV gene usage	666:680	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	50	theme	hypermutation	651:663	arg1	degree					633:638	degree	633:638	degree of somatic hypermutation	633:663	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	50	theme	hypermutation	651:663	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	11	51	from	repertoire	1355:1364	arg1	class-switching					1326:1340	direct class-switching	1319:1340	direct class-switching from the IgM repertoire	1319:1364	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	8	52	theme	IgE	967:969	arg1	sequences					971:979	Many IgE sequences	962:979	Many IgE sequences	962:979	Many IgE sequences contained N-linked glycosylation motifs.
31333671	13	53	theme	pathogenic	1728:1737	arg1	mechanisms					1739:1748	pathogenic mechanisms	1728:1748	pathogenic mechanisms in allergic disease	1728:1768	This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
31333671	5	54	theme	IGHV	666:669	arg1	usage					676:680	IGHV gene usage	666:680	IGHV gene usage	666:680	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	54	theme	IGHV	666:669	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	6	55	theme	preferential	806:817	arg1	usage					819:823	preferential usage	806:823	preferential usage of certain IGHV genes compared to the other isotypes	806:876	IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes.
31333671	5	56	link	N-linked	720:727	arg1	motifs					743:748	N-linked glycosylation motifs	720:748	N-linked glycosylation motifs	720:748	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	56	link	N-linked	720:727	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	1	57	theme	health	170:175	arg1	problem					177:183	an increasing health problem	156:183	an increasing health problem	156:183	IgE-mediated allergic disease represents an increasing health problem.
31333671	8	58	theme	glycosylation	1000:1012	arg1	motifs					1014:1019	N-linked glycosylation motifs	991:1019	N-linked glycosylation motifs	991:1019	Many IgE sequences contained N-linked glycosylation motifs.
31333671	13	59	theme	improved	1784:1791	arg1	strategies					1809:1818	improved desensitization strategies	1784:1818	improved desensitization strategies	1784:1818	This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
31333671	11	60	theme	direct	1319:1324	arg1	class-switching					1326:1340	direct class-switching	1319:1340	direct class-switching from the IgM repertoire	1319:1364	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	5	61	theme	antigenic	695:703	arg1	selection					705:713	antigenic selection	695:713	antigenic selection	695:713	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	7	62	dep	more	901:904	arg1	mutations					914:922	somatic mutations	906:922	somatic mutations	906:922	IgE sequences carried more somatic mutations than IgM, yet fewer than IgG and IgA.
31333671	2	63	theme	IgE	313:315	arg1	repertoire					317:326	the healthy IgE repertoire	301:326	the healthy IgE repertoire	301:326	Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire.
31333671	9	64	contain	had	1036:1038	arg2	relationship					1050:1061	no clonal relationship	1040:1061	no clonal relationship with the other isotypes	1040:1085	IgE sequences had no clonal relationship with the other isotypes.
31333671	9	64	contain	had	1036:1038	arg1	sequences					1026:1034	IgE sequences	1022:1034	IgE sequences	1022:1034	IgE sequences had no clonal relationship with the other isotypes.
31333671	2	65	theme	allergic	247:254	arg1	patients					256:263	allergic patients	247:263	allergic patients	247:263	Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire.
31333671	11	66	theme	IgM	1351:1353	arg1	repertoire					1355:1364	the IgM repertoire	1347:1364	the IgM repertoire	1347:1364	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	12	67	theme	mast	1607:1610	arg1	degranulation					1617:1629	mast cell degranulation	1607:1629	mast cell degranulation induced by allergen-specific, high-affinity IgE	1607:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	9	68	theme	IgE	1022:1024	arg1	sequences					1026:1034	IgE sequences	1022:1034	IgE sequences	1022:1034	IgE sequences had no clonal relationship with the other isotypes.
31333671	1	69	theme	IgE-mediated	115:126	arg1	disease					137:143	IgE-mediated allergic disease	115:143	IgE-mediated allergic disease	115:143	IgE-mediated allergic disease represents an increasing health problem.
31333671	12	70	theme	Fcε	1558:1560	arg1	receptors					1562:1570	Fcε receptors	1558:1570	Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE	1558:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	12	71	dep	allergen-specific	1642:1658	arg1	high-affinity					1661:1673	high-affinity	1661:1673	high-affinity	1661:1673	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	10	72	attach	derived	1133:1139	arg2	repertoire					1096:1105	The IgE repertoire	1088:1105	The IgE repertoire in healthy individuals	1088:1128	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	10	72	attach	derived	1133:1139	arg1	expansions					1168:1177	relatively few clonal expansions	1146:1177	relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA	1146:1253	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	9	73	theme	clonal	1043:1048	arg1	relationship					1050:1061	no clonal relationship	1040:1061	no clonal relationship with the other isotypes	1040:1085	IgE sequences had no clonal relationship with the other isotypes.
31333671	3	74	from	cells	388:392	arg1	transcripts					352:362	IgM, IgG, IgA, and IgE transcripts	329:362	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals	329:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	12	75	with	compatible	1483:1492	arg1	function					1509:1516	a primary function	1499:1516	a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE	1499:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	12	76	theme	IgE	1533:1535	arg1	repertoire					1537:1546	the healthy IgE repertoire	1521:1546	the healthy IgE repertoire	1521:1546	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	4	77	theme	VDJ	513:515	arg1	regions					517:523	Complete VDJ regions	504:523	Complete VDJ regions	504:523	Complete VDJ regions were sequenced to near-exhaustion on the PacBio platform.
31333671	11	78	theme	IgE	1288:1290	arg1	burden					1271:1276	The mutational burden	1256:1276	The mutational burden of normal IgE	1256:1290	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	8	79	contain	contained	981:989	arg1	sequences					971:979	Many IgE sequences	962:979	Many IgE sequences	962:979	Many IgE sequences contained N-linked glycosylation motifs.
31333671	8	79	contain	contained	981:989	arg2	motifs					1014:1019	N-linked glycosylation motifs	991:1019	N-linked glycosylation motifs	991:1019	Many IgE sequences contained N-linked glycosylation motifs.
31333671	5	80	theme	N-linked	720:727	arg1	motifs					743:748	N-linked glycosylation motifs	720:748	N-linked glycosylation motifs	720:748	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	5	80	theme	N-linked	720:727	arg1	relationships					618:630	clonal relationships	611:630	clonal relationships	611:630	Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs.
31333671	9	81	with	relationship	1050:1061	arg1	isotypes					1078:1085	the other isotypes	1068:1085	the other isotypes	1068:1085	IgE sequences had no clonal relationship with the other isotypes.
31333671	3	82	theme	IgE	348:350	arg1	transcripts					352:362	IgM, IgG, IgA, and IgE transcripts	329:362	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals	329:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	13	83	theme	allergic	1753:1760	arg1	disease					1762:1768	allergic disease	1753:1768	allergic disease	1753:1768	This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
31333671	9	84	theme	other	1072:1076	arg1	isotypes					1078:1085	the other isotypes	1068:1085	the other isotypes	1068:1085	IgE sequences had no clonal relationship with the other isotypes.
31333671	0	85	theme	Other	99:103	arg1	Isotypes					105:112	Other Isotypes	99:112	Other Isotypes	99:112	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	11	86	theme	low	1428:1430	arg1	affinity					1432:1439	low affinity	1428:1439	low affinity for specific antigens	1428:1461	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	3	87	theme	individuals	422:432	arg1	cells					388:392	peripheral blood B cells	369:392	peripheral blood B cells of five healthy, non-atopic individuals	369:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	0	88	theme	IgE	11:13	arg1	Repertoires					15:25	Peripheral IgE Repertoires	0:25	Peripheral IgE Repertoires of Healthy Donors	0:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	0	88	theme	IgE	11:13	arg1	Donors					38:43	Healthy Donors	30:43	Healthy Donors	30:43	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	10	89	theme	IgE	1092:1094	arg1	repertoire					1096:1105	The IgE repertoire	1088:1105	The IgE repertoire in healthy individuals	1088:1128	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	3	90	theme	blood	380:384	arg1	cells					388:392	peripheral blood B cells	369:392	peripheral blood B cells of five healthy, non-atopic individuals	369:432	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	12	91	theme	allergen-specific	1642:1658	arg1	IgE					1675:1677	allergen-specific, high-affinity IgE	1642:1677	allergen-specific, high-affinity IgE	1642:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	4	92	theme	PacBio	566:571	arg1	platform					573:580	the PacBio platform	562:580	the PacBio platform	562:580	Complete VDJ regions were sequenced to near-exhaustion on the PacBio platform.
31333671	3	93	theme	unbiased	452:459	arg1	PCR					499:501	unbiased, template-switching, isotype-specific PCR	452:501	unbiased, template-switching, isotype-specific PCR	452:501	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	10	94	from	repertoire	1096:1105	arg1	individuals					1118:1128	healthy individuals	1110:1128	healthy individuals	1110:1128	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	12	95	theme	primary	1501:1507	arg1	function					1509:1516	a primary function	1499:1516	a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE	1499:1677	These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE.
31333671	3	96	dep	healthy	402:408	arg1	non-atopic					411:420	non-atopic	411:420	non-atopic	411:420	IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR.
31333671	11	97	theme	little	1371:1376	arg1	evidence					1378:1385	little evidence	1371:1385	little evidence of antigenic drive	1371:1404	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	0	98	theme	Moderate	51:58	arg1	Loads					69:73	Moderate Mutation Loads	51:73	Moderate Mutation Loads	51:73	Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes.
31333671	10	99	theme	clonal	1161:1166	arg1	expansions					1168:1177	relatively few clonal expansions	1146:1177	relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA	1146:1253	The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA.
31333671	11	100	theme	mutational	1260:1269	arg1	burden					1271:1276	The mutational burden	1256:1276	The mutational burden of normal IgE	1256:1290	The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens.
31333671	13	101	from	mechanisms	1739:1748	arg1	disease					1762:1768	allergic disease	1753:1768	allergic disease	1753:1768	This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.
31333671	7	102	theme	somatic	906:912	arg1	mutations					914:922	somatic mutations	906:922	somatic mutations	906:922	IgE sequences carried more somatic mutations than IgM, yet fewer than IgG and IgA.
31333671	6	103	theme	IGHV	836:839	arg1	genes					841:845	certain IGHV genes	828:845	certain IGHV genes	828:845	IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes.
35518855	6	0	theme	total	881:885	arg1	glycans					896:902	their total N-linked glycans	875:902	their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns	875:986	And we further analyzed their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns.
35518855	2	1	theme	poor	301:304	arg1	sensitivity					306:316	poor sensitivity	301:316	poor sensitivity to therapy and prognosis	301:341	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	4	2	from	levels	551:556	arg1	pairs					584:588	seven pairs	578:588	seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs)	578:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	0	3	from	expression	10:19	arg1	carcinoma					77:85	human lung squamous cell carcinoma	52:85	human lung squamous cell carcinoma	52:85	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	3	4	theme	protein	457:463	arg1	glycosylation					465:477	protein glycosylation	457:477	protein glycosylation	457:477	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	7	5	theme	core	1041:1044	arg1	fucosylation					1046:1057	the core fucosylation	1037:1057	the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA)	1037:1138	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	5	6	theme	Fluorescence-based	676:693	arg1	histochemistry					702:715	Fluorescence-based lectin histochemistry	676:715	Fluorescence-based lectin histochemistry	676:715	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	8	7	gly	fucosylated	1225:1235	arg1	glycans					1246:1252	10 and 15 fucosylated N-linked glycans	1215:1252	10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues	1215:1296	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	10	8	theme	lung	1586:1589	arg1	diseases					1591:1598	the lung diseases	1582:1598	the lung diseases	1582:1598	These finding is helpful to elucidate the molecular mechanisms underlying the lung diseases and develop new treatment strategies.
35518855	4	9	theme	expression	540:549	arg1	levels					551:556	the differential expression levels	523:556	the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs)	523:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	5	10	theme	lectin	695:700	arg1	histochemistry					702:715	Fluorescence-based lectin histochemistry	676:715	Fluorescence-based lectin histochemistry	676:715	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	11	dep	expression	778:787	arg1	the					774:776	the	774:776	the	774:776	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	4	12	theme	differential	527:538	arg1	levels					551:556	the differential expression levels	523:556	the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs)	523:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	5	13	theme	glycans	817:823	arg1	expression					778:787	expression	778:787	expression	778:787	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	13	theme	glycans	817:823	arg1	distribution					793:804	distribution	793:804	distribution	793:804	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	14	from	distribution	793:804	arg1	tissues					833:839	LUSC tissues	828:839	LUSC tissues	828:839	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	14	from	distribution	793:804	arg1	PCTs					845:848	PCTs	845:848	PCTs	845:848	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	15	used	utilized	742:749	arg2	blotting					728:735	lectin blotting	721:735	lectin blotting	721:735	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	15	used	utilized	742:749	arg2	histochemistry					702:715	Fluorescence-based lectin histochemistry	676:715	Fluorescence-based lectin histochemistry	676:715	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	2	16	theme	cell	234:237	arg1	carcinoma					239:247	lung squamous cell carcinoma	220:247	lung squamous cell carcinoma (LUSC)	220:254	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	16	theme	cell	234:237	arg1	types					198:202	the major types	188:202	the major types of lung cancer	188:217	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	16	theme	cell	234:237	arg1	one					181:183	one	181:183	one	181:183	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	16	theme	cell	234:237	arg1	LUSC					250:253	LUSC	250:253	LUSC	250:253	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	6	17	link	N-linked	887:894	arg1	glycans					896:902	their total N-linked glycans	875:902	their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns	875:986	And we further analyzed their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns.
35518855	1	18	theme	cancer	153:158	arg1	cancer					121:126	the most frequent cancer	103:126	the most frequent cancer	103:126	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	1	18	theme	cancer	153:158	arg1	cancer					93:98	Lung cancer	88:98	Lung cancer	88:98	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	1	18	theme	cancer	153:158	arg1	cause					144:148	the leading cause	132:148	the leading cause of cancer around the world	132:175	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	7	19	theme	Lens	1108:1111	arg1	agglutinin					1123:1132	Lens culinaris agglutinin	1108:1132	Lens culinaris agglutinin (LCA)	1108:1138	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	7	19	theme	Lens	1108:1111	arg1	LCA					1135:1137	LCA	1135:1137	LCA	1135:1137	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	2	20	theme	squamous	225:232	arg1	carcinoma					239:247	lung squamous cell carcinoma	220:247	lung squamous cell carcinoma (LUSC)	220:254	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	20	theme	squamous	225:232	arg1	types					198:202	the major types	188:202	the major types of lung cancer	188:217	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	20	theme	squamous	225:232	arg1	one					181:183	one	181:183	one	181:183	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	20	theme	squamous	225:232	arg1	LUSC					250:253	LUSC	250:253	LUSC	250:253	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	4	21	theme	tissues	598:604	arg1	pairs					584:588	seven pairs	578:588	seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs)	578:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	5	22	from	expression	778:787	arg1	tissues					833:839	LUSC tissues	828:839	LUSC tissues	828:839	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	22	from	expression	778:787	arg1	PCTs					845:848	PCTs	845:848	PCTs	845:848	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	5	23	theme	lectin	721:726	arg1	blotting					728:735	lectin blotting	721:735	lectin blotting	721:735	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	1	24	theme	Lung	88:91	arg1	cancer					121:126	the most frequent cancer	103:126	the most frequent cancer	103:126	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	1	24	theme	Lung	88:91	arg1	cancer					93:98	Lung cancer	88:98	Lung cancer	88:98	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	4	25	theme	pericarcinomatous	617:633	arg1	PCTs					644:647	PCTs	644:647	PCTs	644:647	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	4	25	theme	pericarcinomatous	617:633	arg1	tissues					635:641	normal pericarcinomatous tissues	610:641	normal pericarcinomatous tissues (PCTs)	610:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	0	26	theme	Increased	0:8	arg1	expression					10:19	Increased expression	0:19	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma	0:85	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	7	27	theme	Pisum	1073:1077	arg1	PSA					1099:1101	PSA	1099:1101	PSA	1099:1101	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	7	27	theme	Pisum	1073:1077	arg1	agglutinin					1087:1096	Pisum sativum agglutinin	1073:1096	Pisum sativum agglutinin (PSA)	1073:1102	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	5	28	theme	LUSC	828:831	arg1	tissues					833:839	LUSC tissues	828:839	LUSC tissues	828:839	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	3	29	theme	reliable	385:392	arg1	indicators					394:403	reliable indicators	385:403	reliable indicators of cancer	385:413	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	3	29	theme	reliable	385:392	arg1	alteration					353:362	alteration	353:362	alteration of glycopatterns	353:379	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	0	30	theme	core-fucosylated	24:39	arg1	glycans					41:47	core-fucosylated glycans	24:47	core-fucosylated glycans	24:47	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	8	31	theme	LUSC	1398:1401	arg1	tissues					1403:1409	LUSC tissues	1398:1409	LUSC tissues	1398:1409	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	7	32	theme	fucosylation	1046:1057	arg1	level					1028:1032	the expression level	1013:1032	the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA)	1013:1138	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	8	33	theme	fucosylated	1361:1371	arg1	N-glycans					1373:1381	five fucosylated N-glycans	1356:1381	five fucosylated N-glycans	1356:1381	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	8	34	theme	fucosylated	1225:1235	arg1	glycans					1246:1252	10 and 15 fucosylated N-linked glycans	1215:1252	10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues	1215:1296	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	6	35	theme	more	938:941	arg1	information					943:953	more information	938:953	more information about the aberrant glycopatterns	938:986	And we further analyzed their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns.
35518855	8	36	theme	fucosylated	1315:1325	arg1	N-glycans					1327:1335	10 fucosylated N-glycans	1312:1335	10 fucosylated N-glycans	1312:1335	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	8	37	theme	LUSC	1285:1288	arg1	tissues					1290:1296	LUSC tissues	1285:1296	LUSC tissues	1285:1296	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	5	38	theme	certain	809:815	arg1	glycans					817:823	certain glycans	809:823	certain glycans	809:823	Fluorescence-based lectin histochemistry and lectin blotting were utilized to validate and assess the expression and distribution of certain glycans in LUSC tissues and PCTs.
35518855	10	39	theme	molecular	1550:1558	arg1	mechanisms					1560:1569	the molecular mechanisms	1546:1569	the molecular mechanisms underlying the lung diseases	1546:1598	These finding is helpful to elucidate the molecular mechanisms underlying the lung diseases and develop new treatment strategies.
35518855	8	40	gly	fucosylated	1315:1325	arg1	N-glycans					1327:1335	10 fucosylated N-glycans	1312:1335	10 fucosylated N-glycans	1312:1335	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	8	41	located	detected	1264:1271	arg2	glycans					1246:1252	10 and 15 fucosylated N-linked glycans	1215:1252	10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues	1215:1296	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	8	41	located	detected	1264:1271	arg1	PCTs					1276:1279	PCTs	1276:1279	PCTs	1276:1279	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	8	41	located	detected	1264:1271	arg1	tissues					1290:1296	LUSC tissues	1285:1296	LUSC tissues	1285:1296	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	4	42	theme	LUSC	593:596	arg1	tissues					598:604	LUSC tissues	593:604	LUSC tissues	593:604	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	4	43	theme	normal	610:615	arg1	PCTs					644:647	PCTs	644:647	PCTs	644:647	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	4	43	theme	normal	610:615	arg1	tissues					635:641	normal pericarcinomatous tissues	610:641	normal pericarcinomatous tissues (PCTs)	610:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	3	44	theme	cancer	408:413	arg1	indicators					394:403	reliable indicators	385:403	reliable indicators of cancer	385:413	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	3	44	theme	cancer	408:413	arg1	alteration					353:362	alteration	353:362	alteration of glycopatterns	353:379	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	0	45	theme	glycans	41:47	arg1	expression					10:19	Increased expression	0:19	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma	0:85	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	3	46	theme	glycopatterns	367:379	arg1	indicators					394:403	reliable indicators	385:403	reliable indicators of cancer	385:413	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	3	46	theme	glycopatterns	367:379	arg1	alteration					353:362	alteration	353:362	alteration of glycopatterns	353:379	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	2	47	theme	types	198:202	arg1	types					198:202	the major types	188:202	the major types of lung cancer	188:217	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	47	theme	types	198:202	arg1	carcinoma					239:247	lung squamous cell carcinoma	220:247	lung squamous cell carcinoma (LUSC)	220:254	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	47	theme	types	198:202	arg1	one					181:183	one	181:183	one	181:183	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	8	48	theme	N-linked	1237:1244	arg1	glycans					1246:1252	10 and 15 fucosylated N-linked glycans	1215:1252	10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues	1215:1296	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	0	49	theme	lung	58:61	arg1	carcinoma					77:85	human lung squamous cell carcinoma	52:85	human lung squamous cell carcinoma	52:85	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	7	50	theme	LUSC	1171:1174	arg1	tissues					1176:1182	LUSC tissues	1171:1182	LUSC tissues	1171:1182	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	7	51	dep	increased	1158:1166	arg1	compared					1184:1191	compared	1184:1191	compared with PCTs	1184:1201	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	7	52	dep	Pisum	1073:1077	arg1	sativum					1079:1085	sativum	1079:1085	sativum	1079:1085	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	2	53	theme	major	192:196	arg1	types					198:202	the major types	188:202	the major types of lung cancer	188:217	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	4	54	theme	lectin	656:661	arg1	microarrays					663:673	lectin microarrays	656:673	lectin microarrays	656:673	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	0	55	theme	human	52:56	arg1	carcinoma					77:85	human lung squamous cell carcinoma	52:85	human lung squamous cell carcinoma	52:85	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	0	56	gly	core-fucosylated	24:39	arg1	glycans					41:47	core-fucosylated glycans	24:47	core-fucosylated glycans	24:47	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	9	57	theme	N-glycans	1449:1457	arg1	abundance					1420:1428	the abundance	1416:1428	the abundance of the fucosylated N-glycans	1416:1457	And the abundance of the fucosylated N-glycans was increased from 40.9% (PCTs) to 48.3% (LUSC).
35518855	1	58	theme	frequent	112:119	arg1	cancer					121:126	the most frequent cancer	103:126	the most frequent cancer	103:126	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	1	58	theme	frequent	112:119	arg1	cancer					93:98	Lung cancer	88:98	Lung cancer	88:98	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	7	59	theme	culinaris	1113:1121	arg1	agglutinin					1123:1132	Lens culinaris agglutinin	1108:1132	Lens culinaris agglutinin (LCA)	1108:1138	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	7	59	theme	culinaris	1113:1121	arg1	LCA					1135:1137	LCA	1135:1137	LCA	1135:1137	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	8	60	link	N-linked	1237:1244	arg1	glycans					1246:1252	10 and 15 fucosylated N-linked glycans	1215:1252	10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues	1215:1296	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	2	61	theme	lung	220:223	arg1	carcinoma					239:247	lung squamous cell carcinoma	220:247	lung squamous cell carcinoma (LUSC)	220:254	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	61	theme	lung	220:223	arg1	types					198:202	the major types	188:202	the major types of lung cancer	188:217	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	61	theme	lung	220:223	arg1	one					181:183	one	181:183	one	181:183	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	2	61	theme	lung	220:223	arg1	LUSC					250:253	LUSC	250:253	LUSC	250:253	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	4	62	theme	tissues	635:641	arg1	pairs					584:588	seven pairs	578:588	seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs)	578:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
35518855	10	63	theme	treatment	1616:1624	arg1	strategies					1626:1635	new treatment strategies	1612:1635	new treatment strategies	1612:1635	These finding is helpful to elucidate the molecular mechanisms underlying the lung diseases and develop new treatment strategies.
35518855	6	64	theme	aberrant	965:972	arg1	glycopatterns					974:986	the aberrant glycopatterns	961:986	the aberrant glycopatterns	961:986	And we further analyzed their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns.
35518855	7	65	theme	expression	1017:1026	arg1	level					1028:1032	the expression level	1013:1032	the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA)	1013:1138	The results showed that the expression level of the core fucosylation recognized by Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCA) was significantly increased in LUSC tissues compared with PCTs.
35518855	9	66	gly	fucosylated	1437:1447	arg1	N-glycans					1449:1457	the fucosylated N-glycans	1433:1457	the fucosylated N-glycans	1433:1457	And the abundance of the fucosylated N-glycans was increased from 40.9% (PCTs) to 48.3% (LUSC).
35518855	3	67	theme	related	479:485	arg1	alterations					442:452	the alterations	438:452	the alterations of protein glycosylation related to LUSC	438:493	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	0	68	theme	cell	72:75	arg1	carcinoma					77:85	human lung squamous cell carcinoma	52:85	human lung squamous cell carcinoma	52:85	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	9	69	theme	fucosylated	1437:1447	arg1	N-glycans					1449:1457	the fucosylated N-glycans	1433:1457	the fucosylated N-glycans	1433:1457	And the abundance of the fucosylated N-glycans was increased from 40.9% (PCTs) to 48.3% (LUSC).
35518855	2	70	theme	cancer	212:217	arg1	types					198:202	the major types	188:202	the major types of lung cancer	188:217	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	10	71	theme	new	1612:1614	arg1	strategies					1626:1635	new treatment strategies	1612:1635	new treatment strategies	1612:1635	These finding is helpful to elucidate the molecular mechanisms underlying the lung diseases and develop new treatment strategies.
35518855	3	72	theme	glycosylation	465:477	arg1	alterations					442:452	the alterations	438:452	the alterations of protein glycosylation related to LUSC	438:493	Although alteration of glycopatterns are reliable indicators of cancer, little is known about the alterations of protein glycosylation related to LUSC.
35518855	8	73	gly	fucosylated	1361:1371	arg1	N-glycans					1373:1381	five fucosylated N-glycans	1356:1381	five fucosylated N-glycans	1356:1381	There were 10 and 15 fucosylated N-linked glycans that were detected in PCTs and LUSC tissues respectively, 10 fucosylated N-glycans were common, while five fucosylated N-glycans were unique to LUSC tissues.
35518855	0	74	theme	squamous	63:70	arg1	carcinoma					77:85	human lung squamous cell carcinoma	52:85	human lung squamous cell carcinoma	52:85	Increased expression of core-fucosylated glycans in human lung squamous cell carcinoma.
35518855	6	75	theme	N-linked	887:894	arg1	glycans					896:902	their total N-linked glycans	875:902	their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns	875:986	And we further analyzed their total N-linked glycans using MALDI-TOF/TOF-MS to provide more information about the aberrant glycopatterns.
35518855	2	76	theme	lung	207:210	arg1	cancer					212:217	lung cancer	207:217	lung cancer	207:217	As one of the major types of lung cancer, lung squamous cell carcinoma (LUSC) is closely associated with smoking and shows poor sensitivity to therapy and prognosis.
35518855	1	77	theme	leading	136:142	arg1	cause					144:148	the leading cause	132:148	the leading cause of cancer around the world	132:175	Lung cancer is the most frequent cancer and the leading cause of cancer around the world.
35518855	4	78	theme	glycopatterns	561:573	arg1	levels					551:556	the differential expression levels	523:556	the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs)	523:648	In this study, we compared the differential expression levels of glycopatterns in seven pairs of LUSC tissues and normal pericarcinomatous tissues (PCTs) using lectin microarrays.
30623643	6	0	theme	liberal	1064:1070	arg1	production					1078:1087	liberal mucin production	1064:1087	liberal mucin production on the apical surface	1064:1109	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	9	1	theme	bacterial	1660:1668	arg1	communities					1670:1680	host-associated bacterial communities	1644:1680	host-associated bacterial communities	1644:1680	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	10	2	theme	bacterial	1814:1822	arg1	taxa					1824:1827	bacterial taxa	1814:1827	bacterial taxa that degrade host compounds to be identified	1814:1872	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	7	3	link	O-linked	1171:1178	arg1	glycans					1180:1186	O-linked glycans	1171:1186	O-linked glycans	1171:1186	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	2	4	theme	diverse	260:266	arg1	substrates					289:298	diverse isotopically labeled substrates	260:298	diverse isotopically labeled substrates	260:298	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	1	5	theme	powerful	171:178	arg1	tool					180:183	a powerful tool	169:183	a powerful tool to address key questions about microbiota structure and function	169:248	Stable isotope probing (SIP) has emerged as a powerful tool to address key questions about microbiota structure and function.
30623643	4	6	theme	abundant	661:668	arg1	source					670:675	an abundant source	658:675	an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces	658:756	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	8	7	from	incorporation	1443:1455	arg1	oligosaccharides					1494:1509	the heterogeneous O-linked oligosaccharides	1467:1509	the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight	1467:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	1	8	theme	key	196:198	arg1	questions					200:208	key questions	196:208	key questions about microbiota structure and function	196:248	Stable isotope probing (SIP) has emerged as a powerful tool to address key questions about microbiota structure and function.
30623643	3	9	theme	"	593:593	arg1	substrates					603:612	biologically relevant "heavy" labeled substrates	565:612	biologically relevant "heavy" labeled substrates	565:612	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	8	10	theme	heterogeneous	1471:1483	arg1	oligosaccharides					1494:1509	the heterogeneous O-linked oligosaccharides	1467:1509	the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight	1467:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	7	11	theme	time-of-flight	1360:1373	arg1	MALDI-TOF-MS					1394:1405	MALDI-TOF-MS	1394:1405	MALDI-TOF-MS	1394:1405	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	11	theme	time-of-flight	1360:1373	arg1	spectrometry					1380:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry	1316:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)	1316:1406	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	4	12	theme	oral	699:702	arg1	cavity					704:709	oral cavity	699:709	oral cavity	699:709	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	10	13	from	use	1781:1783	arg1	SIP					1788:1790	SIP	1788:1790	SIP	1788:1790	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	7	14	theme	desorption	1338:1347	arg1	MALDI-TOF-MS					1394:1405	MALDI-TOF-MS	1394:1405	MALDI-TOF-MS	1394:1405	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	14	theme	desorption	1338:1347	arg1	spectrometry					1380:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry	1316:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)	1316:1406	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	0	15	theme	Isotope	67:73	arg1	Probing					75:81	Stable Isotope Probing	60:81	Stable Isotope Probing of Host-Associated Microbial Communities	60:122	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	3	16	theme	substrates	603:612	arg1	dearth					555:560	the dearth	551:560	the dearth of biologically relevant "heavy" labeled substrates	551:612	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	3	16	theme	substrates	603:612	arg1	limitation					510:519	A major limitation	502:519	A major limitation to the growth of the field	502:546	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	6	17	theme	adenocarcinoma	963:976	arg1	Calu-3					989:994	Calu-3	989:994	Calu-3	989:994	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	6	17	theme	adenocarcinoma	963:976	arg1	line					983:986	the lung adenocarcinoma cell line	954:986	the lung adenocarcinoma cell line	954:986	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	0	18	theme	Microbial	102:110	arg1	Communities					112:122	Host-Associated Microbial Communities	86:122	Host-Associated Microbial Communities	86:122	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	2	19	theme	labeled	281:287	arg1	substrates					289:298	diverse isotopically labeled substrates	260:298	diverse isotopically labeled substrates	260:298	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	4	20	theme	mucosal	741:747	arg1	surfaces					749:756	other mucosal surfaces	735:756	other mucosal surfaces	735:756	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	7	21	theme	O-linked	1171:1178	arg1	glycans					1180:1186	O-linked glycans	1171:1186	O-linked glycans	1171:1186	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	9	22	theme	heavy	1557:1561	arg1	glycoproteins					1572:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	7	23	theme	laser	1332:1336	arg1	MALDI-TOF-MS					1394:1405	MALDI-TOF-MS	1394:1405	MALDI-TOF-MS	1394:1405	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	23	theme	laser	1332:1336	arg1	spectrometry					1380:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry	1316:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)	1316:1406	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	8	24	theme	dry	1538:1540	arg1	weight					1542:1547	mucin dry weight	1532:1547	mucin dry weight	1532:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	2	25	dep	in	331:332	arg1	situ					334:337	situ	334:337	situ	334:337	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	9	26	theme	labeled	1564:1570	arg1	glycoproteins					1572:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	10	27	theme	host	1842:1845	arg1	compounds					1847:1855	host compounds	1842:1855	host compounds	1842:1855	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	6	28	theme	cell	1007:1010	arg1	cultures					1012:1019	polarized cell cultures	997:1019	polarized cell cultures grown in 13C-labeled d-glucose	997:1050	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	2	29	theme	bioavailable	412:423	arg1	substrates					425:434	bioavailable substrates	412:434	bioavailable substrates	412:434	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	7	30	theme	size-exclusion	1136:1149	arg1	chromatography					1151:1164	size-exclusion chromatography	1136:1164	size-exclusion chromatography	1136:1164	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	1	31	theme	Stable	125:130	arg1	SIP					149:151	SIP	149:151	SIP	149:151	Stable isotope probing (SIP) has emerged as a powerful tool to address key questions about microbiota structure and function.
30623643	1	31	theme	Stable	125:130	arg1	probing					140:146	Stable isotope probing	125:146	Stable isotope probing (SIP)	125:152	Stable isotope probing (SIP) has emerged as a powerful tool to address key questions about microbiota structure and function.
30623643	7	32	theme	mass	1282:1285	arg1	ESI-MS/MS					1301:1309	ESI-MS/MS	1301:1309	ESI-MS/MS	1301:1309	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	32	theme	mass	1282:1285	arg1	spectrometry					1287:1298	electrospray ionization tandem mass spectrometry	1251:1298	electrospray ionization tandem mass spectrometry (ESI-MS/MS)	1251:1310	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	0	33	theme	Mucin	33:37	arg1	Oligosaccharides					39:54	13C-Labeled MUC5AC Mucin Oligosaccharides	14:54	13C-Labeled MUC5AC Mucin Oligosaccharides	14:54	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	9	34	theme	valuable	1598:1605	arg1	tool					1607:1610	a valuable tool	1596:1610	a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier	1596:1728	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	6	35	theme	polarized	997:1005	arg1	cultures					1012:1019	polarized cell cultures	997:1019	polarized cell cultures grown in 13C-labeled d-glucose	997:1050	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	10	36	dep	health	1913:1918	arg1	management					1932:1941	management	1932:1941	management	1932:1941	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	2	37	theme	growth	339:344	arg1	activity					346:353	in situ growth activity	331:353	in situ growth activity of specific bacterial taxa	331:380	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	6	38	theme	apical	1096:1101	arg1	surface					1103:1109	the apical surface	1092:1109	the apical surface	1092:1109	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	9	39	gly	glycoproteins	1572:1584	arg1	glycoproteins					1572:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	8	40	theme	98.7	1437:1440	arg1	%					1441:1441	%	1441:1441	%	1441:1441	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	2	41	theme	in	331:332	arg1	activity					346:353	in situ growth activity	331:353	in situ growth activity of specific bacterial taxa	331:380	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	1	42	theme	microbiota	216:225	arg1	structure					227:235	microbiota structure	216:235	microbiota structure	216:235	Stable isotope probing (SIP) has emerged as a powerful tool to address key questions about microbiota structure and function.
30623643	10	43	theme	labeled	1758:1764	arg1	substrates					1766:1775	labeled substrates	1758:1775	labeled substrates for use in SIP	1758:1790	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	9	44	theme	in	1624:1625	arg1	activity					1632:1639	in vivo activity	1624:1639	in vivo activity of host-associated bacterial communities	1624:1680	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	7	45	theme	electrospray	1251:1262	arg1	ESI-MS/MS					1301:1309	ESI-MS/MS	1301:1309	ESI-MS/MS	1301:1309	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	45	theme	electrospray	1251:1262	arg1	spectrometry					1287:1298	electrospray ionization tandem mass spectrometry	1251:1298	electrospray ionization tandem mass spectrometry (ESI-MS/MS)	1251:1310	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	2	46	used	used	310:313	arg2	substrates					289:298	diverse isotopically labeled substrates	260:298	diverse isotopically labeled substrates	260:298	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	10	47	theme	long-term	1880:1888	arg1	potential					1890:1898	long-term potential	1880:1898	long-term potential for improved health and disease management	1880:1941	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	2	48	theme	bacterial	367:375	arg1	taxa					377:380	specific bacterial taxa	358:380	specific bacterial taxa	358:380	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	7	49	theme	analyzed	1239:1246	arg1	techniques					1408:1417	β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques	1205:1417	β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques	1205:1417	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	10	50	theme	continued	1735:1743	arg1	expansion					1745:1753	The continued expansion	1731:1753	The continued expansion of labeled substrates for use in SIP	1731:1790	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	9	51	theme	host-associated	1644:1658	arg1	communities					1670:1680	host-associated bacterial communities	1644:1680	host-associated bacterial communities	1644:1680	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	3	52	theme	field	542:546	arg1	growth					528:533	the growth	524:533	the growth of the field	524:546	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	4	53	from	source	670:675	arg1	gut					694:696	the gut	690:696	the gut	690:696	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	4	53	from	source	670:675	arg1	cavity					704:709	oral cavity	699:709	oral cavity	699:709	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	4	53	from	source	670:675	arg1	tract					724:728	respiratory tract	712:728	respiratory tract	712:728	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	4	53	from	source	670:675	arg1	surfaces					749:756	other mucosal surfaces	735:756	other mucosal surfaces	735:756	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	9	54	theme	communities	1670:1680	arg1	interactions					1692:1703	their interactions	1686:1703	their interactions with the mucosal barrier	1686:1728	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	9	54	theme	communities	1670:1680	arg1	activity					1632:1639	in vivo activity	1624:1639	in vivo activity of host-associated bacterial communities	1624:1680	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	9	55	with	interactions	1692:1703	arg1	barrier					1722:1728	the mucosal barrier	1710:1728	the mucosal barrier	1710:1728	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	4	56	gly	glycoproteins	621:633	arg1	glycoproteins					621:633	Mucin glycoproteins	615:633	Mucin glycoproteins	615:633	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	10	57	theme	substrates	1766:1775	arg1	expansion					1745:1753	The continued expansion	1731:1753	The continued expansion of labeled substrates for use in SIP	1731:1790	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	9	58	theme	mucosal	1714:1720	arg1	barrier					1722:1728	the mucosal barrier	1710:1728	the mucosal barrier	1710:1728	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	8	59	theme	13C	1460:1462	arg1	incorporation					1443:1455	a 98.7% incorporation	1435:1455	a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight	1435:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	5	60	dep	both	901:904	arg1	gastrointestinal					906:921	gastrointestinal	906:921	gastrointestinal	906:921	Here, we describe a method to incorporate a 13C-labeled monosaccharide into MUC5AC, a predominant mucin in both gastrointestinal and airway environments.
30623643	7	61	theme	tandem	1275:1280	arg1	ESI-MS/MS					1301:1309	ESI-MS/MS	1301:1309	ESI-MS/MS	1301:1309	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	61	theme	tandem	1275:1280	arg1	spectrometry					1287:1298	electrospray ionization tandem mass spectrometry	1251:1298	electrospray ionization tandem mass spectrometry (ESI-MS/MS)	1251:1310	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	3	62	theme	heavy	588:592	arg1	substrates					603:612	biologically relevant "heavy" labeled substrates	565:612	biologically relevant "heavy" labeled substrates	565:612	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	9	63	dep	in	1624:1625	arg1	vivo					1627:1630	vivo	1627:1630	vivo	1627:1630	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	3	64	theme	relevant	578:585	arg1	substrates					603:612	biologically relevant "heavy" labeled substrates	565:612	biologically relevant "heavy" labeled substrates	565:612	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	1	65	theme	isotope	132:138	arg1	SIP					149:151	SIP	149:151	SIP	149:151	Stable isotope probing (SIP) has emerged as a powerful tool to address key questions about microbiota structure and function.
30623643	1	65	theme	isotope	132:138	arg1	probing					140:146	Stable isotope probing	125:146	Stable isotope probing (SIP)	125:152	Stable isotope probing (SIP) has emerged as a powerful tool to address key questions about microbiota structure and function.
30623643	8	66	theme	O-linked	1485:1492	arg1	oligosaccharides					1494:1509	the heterogeneous O-linked oligosaccharides	1467:1509	the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight	1467:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	5	67	theme	predominant	880:890	arg1	MUC5AC					870:875	MUC5AC	870:875	MUC5AC	870:875	Here, we describe a method to incorporate a 13C-labeled monosaccharide into MUC5AC, a predominant mucin in both gastrointestinal and airway environments.
30623643	5	67	theme	predominant	880:890	arg1	mucin					892:896	a predominant mucin	878:896	a predominant mucin in both gastrointestinal and airway environments	878:945	Here, we describe a method to incorporate a 13C-labeled monosaccharide into MUC5AC, a predominant mucin in both gastrointestinal and airway environments.
30623643	7	68	theme	mass	1375:1378	arg1	MALDI-TOF-MS					1394:1405	MALDI-TOF-MS	1394:1405	MALDI-TOF-MS	1394:1405	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	68	theme	mass	1375:1378	arg1	spectrometry					1380:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry	1316:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)	1316:1406	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	5	69	dep	environments	934:945	arg1	both					901:904	both	901:904	both	901:904	Here, we describe a method to incorporate a 13C-labeled monosaccharide into MUC5AC, a predominant mucin in both gastrointestinal and airway environments.
30623643	5	69	dep	environments	934:945	arg1	airway					927:932	airway	927:932	airway	927:932	Here, we describe a method to incorporate a 13C-labeled monosaccharide into MUC5AC, a predominant mucin in both gastrointestinal and airway environments.
30623643	7	70	theme	β-elimination	1205:1217	arg1	techniques					1408:1417	β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques	1205:1417	β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques	1205:1417	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	3	71	theme	labeled	595:601	arg1	substrates					603:612	biologically relevant "heavy" labeled substrates	565:612	biologically relevant "heavy" labeled substrates	565:612	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	5	72	theme	13C-labeled	838:848	arg1	monosaccharide					850:863	a 13C-labeled monosaccharide	836:863	a 13C-labeled monosaccharide	836:863	Here, we describe a method to incorporate a 13C-labeled monosaccharide into MUC5AC, a predominant mucin in both gastrointestinal and airway environments.
30623643	7	73	theme	ionization	1349:1358	arg1	MALDI-TOF-MS					1394:1405	MALDI-TOF-MS	1394:1405	MALDI-TOF-MS	1394:1405	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	73	theme	ionization	1349:1358	arg1	spectrometry					1380:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry	1316:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)	1316:1406	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	0	74	theme	Host-Associated	86:100	arg1	Communities					112:122	Host-Associated Microbial Communities	86:122	Host-Associated Microbial Communities	86:122	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	0	75	theme	13C-Labeled	14:24	arg1	Oligosaccharides					39:54	13C-Labeled MUC5AC Mucin Oligosaccharides	14:54	13C-Labeled MUC5AC Mucin Oligosaccharides	14:54	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	6	76	theme	cell	978:981	arg1	Calu-3					989:994	Calu-3	989:994	Calu-3	989:994	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	6	76	theme	cell	978:981	arg1	line					983:986	the lung adenocarcinoma cell line	954:986	the lung adenocarcinoma cell line	954:986	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	4	77	theme	carbon	680:685	arg1	source					670:675	an abundant source	658:675	an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces	658:756	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	0	78	theme	Communities	112:122	arg1	Probing					75:81	Stable Isotope Probing	60:81	Stable Isotope Probing of Host-Associated Microbial Communities	60:122	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	6	79	theme	lung	958:961	arg1	Calu-3					989:994	Calu-3	989:994	Calu-3	989:994	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	6	79	theme	lung	958:961	arg1	line					983:986	the lung adenocarcinoma cell line	954:986	the lung adenocarcinoma cell line	954:986	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	8	80	theme	mucin	1532:1536	arg1	weight					1542:1547	mucin dry weight	1532:1547	mucin dry weight	1532:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	7	81	theme	matrix-assisted	1316:1330	arg1	MALDI-TOF-MS					1394:1405	MALDI-TOF-MS	1394:1405	MALDI-TOF-MS	1394:1405	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	81	theme	matrix-assisted	1316:1330	arg1	spectrometry					1380:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry	1316:1391	matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS)	1316:1406	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	8	82	theme	weight	1542:1547	arg1	%					1527:1527	>80%	1524:1527	>80% of mucin dry weight	1524:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	8	82	theme	weight	1542:1547	arg1	weight					1542:1547	mucin dry weight	1532:1547	mucin dry weight	1532:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	4	83	theme	other	735:739	arg1	surfaces					749:756	other mucosal surfaces	735:756	other mucosal surfaces	735:756	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	5	84	from	mucin	892:896	arg1	environments					934:945	both gastrointestinal and airway environments	901:945	both gastrointestinal and airway environments	901:945	Here, we describe a method to incorporate a 13C-labeled monosaccharide into MUC5AC, a predominant mucin in both gastrointestinal and airway environments.
30623643	9	85	theme	"	1562:1562	arg1	glycoproteins					1572:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins	1550:1584	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	6	86	theme	13C-labeled	1030:1040	arg1	d-glucose					1042:1050	13C-labeled d-glucose	1030:1050	13C-labeled d-glucose	1030:1050	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	2	87	theme	microbial	444:452	arg1	communities					454:464	microbial communities	444:464	microbial communities associated with health and disease	444:499	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	2	88	theme	taxa	377:380	arg1	activity					346:353	in situ growth activity	331:353	in situ growth activity of specific bacterial taxa	331:380	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	0	89	theme	MUC5AC	26:31	arg1	Oligosaccharides					39:54	13C-Labeled MUC5AC Mucin Oligosaccharides	14:54	13C-Labeled MUC5AC Mucin Oligosaccharides	14:54	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	2	90	theme	substrates	425:434	arg1	flux					404:407	the flux	400:407	the flux of bioavailable substrates through microbial communities associated with health and disease	400:499	To date, diverse isotopically labeled substrates have been used to characterize in situ growth activity of specific bacterial taxa and have revealed the flux of bioavailable substrates through microbial communities associated with health and disease.
30623643	4	91	theme	respiratory	712:722	arg1	tract					724:728	respiratory tract	712:728	respiratory tract	712:728	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	0	92	theme	Oligosaccharides	39:54	arg1	Generation					0:9	Generation	0:9	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.	0:123	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	8	93	link	O-linked	1485:1492	arg1	oligosaccharides					1494:1509	the heterogeneous O-linked oligosaccharides	1467:1509	the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight	1467:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	0	94	theme	Stable	60:65	arg1	Probing					75:81	Stable Isotope Probing	60:81	Stable Isotope Probing of Host-Associated Microbial Communities	60:122	Generation of 13C-Labeled MUC5AC Mucin Oligosaccharides for Stable Isotope Probing of Host-Associated Microbial Communities.
30623643	7	95	theme	ionization	1264:1273	arg1	ESI-MS/MS					1301:1309	ESI-MS/MS	1301:1309	ESI-MS/MS	1301:1309	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	7	95	theme	ionization	1264:1273	arg1	spectrometry					1287:1298	electrospray ionization tandem mass spectrometry	1251:1298	electrospray ionization tandem mass spectrometry (ESI-MS/MS)	1251:1310	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
30623643	10	96	theme	improved	1904:1911	arg1	health					1913:1918	improved health	1904:1918	improved health	1904:1918	The continued expansion of labeled substrates for use in SIP will eventually allow bacterial taxa that degrade host compounds to be identified, with long-term potential for improved health and disease management.
30623643	3	97	theme	major	504:508	arg1	dearth					555:560	the dearth	551:560	the dearth of biologically relevant "heavy" labeled substrates	551:612	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	3	97	theme	major	504:508	arg1	limitation					510:519	A major limitation	502:519	A major limitation to the growth of the field	502:546	A major limitation to the growth of the field is the dearth of biologically relevant "heavy" labeled substrates.
30623643	6	98	theme	mucin	1072:1076	arg1	production					1078:1087	liberal mucin production	1064:1087	liberal mucin production on the apical surface	1064:1109	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	4	99	theme	Mucin	615:619	arg1	glycoproteins					621:633	Mucin glycoproteins	615:633	Mucin glycoproteins	615:633	Mucin glycoproteins, for example, comprise an abundant source of carbon in the gut, oral cavity, respiratory tract, and other mucosal surfaces but are not commercially available.
30623643	9	100	with	activity	1632:1639	arg1	barrier					1722:1728	the mucosal barrier	1710:1728	the mucosal barrier	1710:1728	These "heavy" labeled glycoproteins represent a valuable tool for probing in vivo activity of host-associated bacterial communities and their interactions with the mucosal barrier.
30623643	8	101	theme	%	1441:1441	arg1	incorporation					1443:1455	a 98.7% incorporation	1435:1455	a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight	1435:1547	We demonstrate a 98.7% incorporation of 13C in the heterogeneous O-linked oligosaccharides that make up >80% of mucin dry weight.
30623643	6	102	from	production	1078:1087	arg1	surface					1103:1109	the apical surface	1092:1109	the apical surface	1092:1109	Using the lung adenocarcinoma cell line, Calu-3, polarized cell cultures grown in 13C-labeled d-glucose resulted in liberal mucin production on the apical surface.
30623643	7	103	theme	permethylated	1220:1232	arg1	techniques					1408:1417	β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques	1205:1417	β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques	1205:1417	Mucins were isolated by size-exclusion chromatography, and O-linked glycans were released by β-elimination, permethylated, and analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques.
29295913	4	0	theme	yeast	639:643	arg1	cells					645:649	Histoplasma yeast cells	627:649	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins,	627:756	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	7	1	theme	cells	1217:1221	arg1	virulence					1187:1195	the virulence	1183:1195	the virulence of the mutant yeast cells	1183:1221	Depletion of macrophages or neutrophils in vivo does not recover the virulence of the mutant yeast cells.
29295913	10	2	theme	contrasting	1839:1849	arg1	roles					1851:1855	contrasting roles	1839:1855	contrasting roles	1839:1855	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	9	3	theme	mice	1488:1491	arg1	temperature					1473:1483	the normal core body temperature	1452:1483	the normal core body temperature of mice	1452:1491	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	7	4	theme	mutant	1204:1209	arg1	cells					1217:1221	the mutant yeast cells	1200:1221	the mutant yeast cells	1200:1221	Depletion of macrophages or neutrophils in vivo does not recover the virulence of the mutant yeast cells.
29295913	8	5	theme	Pmt	1257:1259	arg1	functions					1261:1269	Pmt functions	1257:1269	Pmt functions	1257:1269	We show that yeast cells lacking Pmt functions are more sensitive to thermal stress in vitro and consequently are unable to productively infect mice, even in the absence of fever.
29295913	4	6	theme	O-linked	722:729	arg1	mannosylation					731:743	O-linked mannosylation	722:743	O-linked mannosylation of proteins	722:755	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	10	7	theme	cells	1706:1710	arg1	thermotolerance					1669:1683	the thermotolerance	1665:1683	the thermotolerance	1665:1683	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	2	8	theme	conidia	327:333	arg1	differentiation					297:311	differentiation	297:311	differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells	297:427	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	10	9	theme	Histoplasma	1688:1698	arg1	cells					1706:1710	Histoplasma yeast cells	1688:1710	Histoplasma yeast cells	1688:1710	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	11	10	theme	Histoplasma	1932:1942	arg1	capsulatum					1944:1953	the fungal pathogen Histoplasma capsulatum	1912:1953	the fungal pathogen Histoplasma capsulatum	1912:1953	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	13	11	theme	mammalian	2306:2314	arg1	hosts					2316:2320	mammalian hosts	2306:2320	mammalian hosts	2306:2320	By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on H. capsulatum, enabling infection of mammalian hosts.
29295913	2	12	theme	mycelia	316:322	arg1	differentiation					297:311	differentiation	297:311	differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells	297:427	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	8	13	theme	thermal	1293:1299	arg1	stress					1301:1306	thermal stress	1293:1306	thermal stress	1293:1306	We show that yeast cells lacking Pmt functions are more sensitive to thermal stress in vitro and consequently are unable to productively infect mice, even in the absence of fever.
29295913	1	14	theme	mammalian	118:126	arg1	temperatures					133:144	mammalian body temperatures	118:144	mammalian body temperatures	118:144	The ability to grow at mammalian body temperatures is critical for pathogen infection of humans.
29295913	2	15	theme	Histoplasma	236:246	arg1	capsulatum					248:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	5	16	theme	mannose	934:940	arg1	receptor					942:949	the macrophage mannose receptor	919:949	the macrophage mannose receptor	919:949	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	12	17	theme	many	2115:2118	arg1	microbes					2120:2127	many microbes	2115:2127	many microbes	2115:2127	On the other hand, elevated temperatures represent a significant barrier to infection by many microbes.
29295913	6	18	theme	yeast	1032:1036	arg1	cells					1038:1042	yeast cells	1032:1042	yeast cells lacking these factors	1032:1064	Despite these changes, yeast cells lacking these factors still associate with and survive within phagocytes.
29295913	4	19	link	O-linked	722:729	arg1	mannosylation					731:743	O-linked mannosylation	722:743	O-linked mannosylation of proteins	722:755	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	11	20	theme	pathogenic	1962:1971	arg1	state					1973:1977	a pathogenic state	1960:1977	a pathogenic state characterized by infection of host phagocytes	1960:2023	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	7	21	theme	neutrophils	1146:1156	arg1	Depletion					1118:1126	Depletion	1118:1126	Depletion of macrophages or neutrophils in vivo	1118:1164	Depletion of macrophages or neutrophils in vivo does not recover the virulence of the mutant yeast cells.
29295913	2	22	theme	fungal	220:225	arg1	capsulatum					248:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	9	23	theme	O-mannosylation-deficient	1556:1580	arg1	cells					1588:1592	O-mannosylation-deficient yeast cells	1556:1592	O-mannosylation-deficient yeast cells	1556:1592	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	7	24	theme	macrophages	1131:1141	arg1	Depletion					1118:1126	Depletion	1118:1126	Depletion of macrophages or neutrophils in vivo	1118:1164	Depletion of macrophages or neutrophils in vivo does not recover the virulence of the mutant yeast cells.
29295913	9	25	theme	cells	1588:1592	arg1	infectivity					1541:1551	the infectivity	1537:1551	the infectivity of O-mannosylation-deficient yeast cells	1537:1592	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	1	26	theme	body	128:131	arg1	temperatures					133:144	mammalian body temperatures	118:144	mammalian body temperatures	118:144	The ability to grow at mammalian body temperatures is critical for pathogen infection of humans.
29295913	11	27	theme	body	1868:1871	arg1	temperature					1873:1883	Mammalian body temperature	1858:1883	Mammalian body temperature	1858:1883	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	0	28	theme	Mammalian	66:74	arg1	Temperatures					81:92	Mammalian Body Temperatures	66:92	Mammalian Body Temperatures	66:92	O-Mannosylation of Proteins Enables Histoplasma Yeast Survival at Mammalian Body Temperatures.
29295913	5	29	theme	cells	910:914	arg1	recognition					889:899	recognition	889:899	recognition of yeast cells by the macrophage mannose receptor	889:949	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	5	30	contain	have	838:841	arg1	Cells					819:823	Cells	819:823	Cells lacking Pmt2	819:836	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	5	30	contain	have	838:841	arg2	characteristics					859:873	altered surface characteristics	843:873	altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1	843:1006	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	10	31	gly	O-mannosylation	1627:1641	arg1	proteins					1646:1653	proteins	1646:1653	proteins	1646:1653	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	8	32	theme	fever	1397:1401	arg1	absence					1386:1392	the absence	1382:1392	the absence of fever	1382:1401	We show that yeast cells lacking Pmt functions are more sensitive to thermal stress in vitro and consequently are unable to productively infect mice, even in the absence of fever.
29295913	11	33	theme	fungal	1916:1921	arg1	capsulatum					1944:1953	the fungal pathogen Histoplasma capsulatum	1912:1953	the fungal pathogen Histoplasma capsulatum	1912:1953	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	5	34	theme	altered	843:849	arg1	characteristics					859:873	altered surface characteristics	843:873	altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1	843:1006	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	1	35	theme	pathogen	162:169	arg1	infection					171:179	pathogen infection	162:179	pathogen infection of humans	162:189	The ability to grow at mammalian body temperatures is critical for pathogen infection of humans.
29295913	12	36	theme	significant	2079:2089	arg1	barrier					2091:2097	a significant barrier	2077:2097	a significant barrier to infection by many microbes	2077:2127	On the other hand, elevated temperatures represent a significant barrier to infection by many microbes.
29295913	10	37	theme	dimorphic	1775:1783	arg1	pathogens					1792:1800	dimorphic fungal pathogens	1775:1800	dimorphic fungal pathogens	1775:1800	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	13	38	theme	protein	2220:2226	arg1	mannosylation					2228:2240	protein mannosylation	2220:2240	protein mannosylation	2220:2240	By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on H. capsulatum, enabling infection of mammalian hosts.
29295913	0	39	theme	Yeast	48:52	arg1	Survival					54:61	Histoplasma Yeast Survival	36:61	Histoplasma Yeast Survival	36:61	O-Mannosylation of Proteins Enables Histoplasma Yeast Survival at Mammalian Body Temperatures.
29295913	2	40	theme	yeast	340:344	arg1	cells					346:350	yeast cells	340:350	yeast cells	340:350	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	2	40	theme	yeast	340:344	arg1	step					355:358	a step	353:358	a step critical for invasion and replication within phagocytic immune cells	353:427	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	4	41	theme	hosts	812:816	arg1	infection					789:797	infection	789:797	infection of mammalian hosts	789:816	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	10	42	theme	hosts.IMPORTANCE	1754:1769	arg1	infection					1731:1739	infection	1731:1739	infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens	1731:1800	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	12	43	theme	elevated	2045:2052	arg1	temperatures					2054:2065	elevated temperatures	2045:2065	elevated temperatures	2045:2065	On the other hand, elevated temperatures represent a significant barrier to infection by many microbes.
29295913	10	44	theme	mammalian	1803:1811	arg1	temperature					1818:1828	mammalian body temperature	1803:1828	mammalian body temperature	1803:1828	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	0	45	theme	Proteins	19:26	arg1	O-Mannosylation					0:14	O-Mannosylation	0:14	O-Mannosylation of Proteins	0:26	O-Mannosylation of Proteins Enables Histoplasma Yeast Survival at Mammalian Body Temperatures.
29295913	0	46	theme	Histoplasma	36:46	arg1	Survival					54:61	Histoplasma Yeast Survival	36:61	Histoplasma Yeast Survival	36:61	O-Mannosylation of Proteins Enables Histoplasma Yeast Survival at Mammalian Body Temperatures.
29295913	3	47	theme	Posttranslational	430:446	arg1	glycosylation					448:460	Posttranslational glycosylation	430:460	Posttranslational glycosylation of extracellular proteins	430:486	Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.
29295913	3	48	theme	extracellular	465:477	arg1	proteins					479:486	extracellular proteins	465:486	extracellular proteins	465:486	Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.
29295913	11	49	theme	host	2009:2012	arg1	phagocytes					2014:2023	host phagocytes	2009:2023	host phagocytes	2009:2023	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	11	50	theme	Mammalian	1858:1866	arg1	temperature					1873:1883	Mammalian body temperature	1858:1883	Mammalian body temperature	1858:1883	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	9	51	theme	normal	1456:1461	arg1	temperature					1473:1483	the normal core body temperature	1452:1483	the normal core body temperature of mice	1452:1491	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	10	52	theme	proteins	1646:1653	arg1	O-mannosylation					1627:1641	O-mannosylation	1627:1641	O-mannosylation of proteins	1627:1653	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	2	53	theme	immune	416:421	arg1	cells					423:427	phagocytic immune cells	405:427	phagocytic immune cells	405:427	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	9	54	theme	body	1468:1471	arg1	temperature					1473:1483	the normal core body temperature	1452:1483	the normal core body temperature of mice	1452:1491	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	7	55	theme	yeast	1211:1215	arg1	cells					1217:1221	the mutant yeast cells	1200:1221	the mutant yeast cells	1200:1221	Depletion of macrophages or neutrophils in vivo does not recover the virulence of the mutant yeast cells.
29295913	13	56	theme	O-linked	2175:2182	arg1	enzymes					2198:2204	O-linked mannosylation enzymes	2175:2204	O-linked mannosylation enzymes	2175:2204	By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on H. capsulatum, enabling infection of mammalian hosts.
29295913	2	57	theme	critical	360:367	arg1	cells					346:350	yeast cells	340:350	yeast cells	340:350	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	2	57	theme	critical	360:367	arg1	step					355:358	a step	353:358	a step critical for invasion and replication within phagocytic immune cells	353:427	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	4	58	theme	Histoplasma	627:637	arg1	cells					645:649	Histoplasma yeast cells	627:649	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins,	627:756	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	4	59	gly	mannosylation	731:743	arg1	proteins					748:755	proteins	748:755	proteins	748:755	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	8	60	theme	yeast	1237:1241	arg1	cells					1243:1247	yeast cells	1237:1247	yeast cells lacking Pmt functions	1237:1269	We show that yeast cells lacking Pmt functions are more sensitive to thermal stress in vitro and consequently are unable to productively infect mice, even in the absence of fever.
29295913	3	61	theme	yeast	537:541	arg1	cells					543:547	the pathogenic yeast cells	522:547	the pathogenic yeast cells but not those of avirulent mycelia	522:582	Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.
29295913	3	62	theme	avirulent	566:574	arg1	mycelia					576:582	avirulent mycelia	566:582	avirulent mycelia	566:582	Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.
29295913	1	63	theme	humans	184:189	arg1	infection					171:179	pathogen infection	162:179	pathogen infection of humans	162:189	The ability to grow at mammalian body temperatures is critical for pathogen infection of humans.
29295913	10	64	theme	yeast	1700:1704	arg1	cells					1706:1710	Histoplasma yeast cells	1688:1710	Histoplasma yeast cells	1688:1710	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	9	65	with	Treatment	1404:1412	arg1	cyclophosphamide					1427:1442	cyclophosphamide	1427:1442	cyclophosphamide	1427:1442	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	5	66	theme	receptor	990:997	arg1	Dectin-1					999:1006	the β-glucan receptor Dectin-1	977:1006	the β-glucan receptor Dectin-1	977:1006	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	4	67	theme	protein	677:683	arg1	mannosyltransferases					685:704	the Pmt1 and Pmt2 protein mannosyltransferases	659:704	mannosyltransferases	685:704	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	11	68	theme	capsulatum	1944:1953	arg1	differentiation					1893:1907	differentiation	1893:1907	differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes	1893:2023	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	13	69	theme	hosts	2316:2320	arg1	infection					2293:2301	infection	2293:2301	infection of mammalian hosts	2293:2320	By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on H. capsulatum, enabling infection of mammalian hosts.
29295913	5	70	theme	macrophage	923:932	arg1	receptor					942:949	the macrophage mannose receptor	919:949	the macrophage mannose receptor	919:949	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	10	71	contain	have	1834:1837	arg2	roles					1851:1855	contrasting roles	1839:1855	contrasting roles	1839:1855	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	10	71	contain	have	1834:1837	arg1	temperature					1818:1828	mammalian body temperature	1803:1828	mammalian body temperature	1803:1828	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	2	72	theme	pathogen	227:234	arg1	capsulatum					248:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	9	73	theme	yeast	1582:1586	arg1	cells					1588:1592	O-mannosylation-deficient yeast cells	1556:1592	O-mannosylation-deficient yeast cells	1556:1592	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	0	74	theme	Body	76:79	arg1	Temperatures					81:92	Mammalian Body Temperatures	66:92	Mammalian Body Temperatures	66:92	O-Mannosylation of Proteins Enables Histoplasma Yeast Survival at Mammalian Body Temperatures.
29295913	2	75	theme	elevated	260:267	arg1	temperature					269:279	elevated temperature	260:279	elevated temperature	260:279	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	4	76	theme	proteins	748:755	arg1	mannosylation					731:743	O-linked mannosylation	722:743	O-linked mannosylation of proteins	722:755	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	5	77	theme	β-glucan	981:988	arg1	Dectin-1					999:1006	the β-glucan receptor Dectin-1	977:1006	the β-glucan receptor Dectin-1	977:1006	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	11	78	theme	pathogen	1923:1930	arg1	capsulatum					1944:1953	the fungal pathogen Histoplasma capsulatum	1912:1953	the fungal pathogen Histoplasma capsulatum	1912:1953	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	10	79	theme	body	1813:1816	arg1	temperature					1818:1828	mammalian body temperature	1803:1828	mammalian body temperature	1803:1828	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	3	80	theme	proteins	479:486	arg1	glycosylation					448:460	Posttranslational glycosylation	430:460	Posttranslational glycosylation of extracellular proteins	430:486	Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.
29295913	4	81	theme	mammalian	802:810	arg1	hosts					812:816	mammalian hosts	802:816	mammalian hosts	802:816	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	10	82	theme	mammalian	1744:1752	arg1	hosts.IMPORTANCE					1754:1769	mammalian hosts.IMPORTANCE	1744:1769	mammalian hosts.IMPORTANCE	1744:1769	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	5	83	theme	yeast	904:908	arg1	cells					910:914	yeast cells	904:914	yeast cells	904:914	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	13	84	link	O-linked	2175:2182	arg1	enzymes					2198:2204	O-linked mannosylation enzymes	2175:2204	O-linked mannosylation enzymes	2175:2204	By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on H. capsulatum, enabling infection of mammalian hosts.
29295913	5	85	theme	surface	851:857	arg1	characteristics					859:873	altered surface characteristics	843:873	altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1	843:1006	Cells lacking Pmt2 have altered surface characteristics that increase recognition of yeast cells by the macrophage mannose receptor and reduce recognition by the β-glucan receptor Dectin-1.
29295913	9	86	theme	mice	1417:1420	arg1	Treatment					1404:1412	Treatment	1404:1412	Treatment of mice with cyclophosphamide	1404:1442	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	12	87	theme	other	2033:2037	arg1	hand					2039:2042	the other hand	2029:2042	the other hand	2029:2042	On the other hand, elevated temperatures represent a significant barrier to infection by many microbes.
29295913	2	88	theme	phagocytic	405:414	arg1	cells					423:427	phagocytic immune cells	405:427	phagocytic immune cells	405:427	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	13	89	theme	mannosylation	2184:2196	arg1	enzymes					2198:2204	O-linked mannosylation enzymes	2175:2204	O-linked mannosylation enzymes	2175:2204	By functionally characterizing cells lacking O-linked mannosylation enzymes, we show that protein mannosylation confers thermotolerance on H. capsulatum, enabling infection of mammalian hosts.
29295913	10	90	theme	fungal	1785:1790	arg1	pathogens					1792:1800	dimorphic fungal pathogens	1775:1800	dimorphic fungal pathogens	1775:1800	These findings demonstrate that O-mannosylation of proteins increases the thermotolerance of Histoplasma yeast cells, which facilitates infection of mammalian hosts.IMPORTANCE For dimorphic fungal pathogens, mammalian body temperature can have contrasting roles.
29295913	2	91	theme	dimorphic	210:218	arg1	capsulatum					248:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	the thermally dimorphic fungal pathogen Histoplasma capsulatum	196:257	For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells.
29295913	11	92	theme	phagocytes	2014:2023	arg1	infection					1996:2004	infection	1996:2004	infection of host phagocytes	1996:2023	Mammalian body temperature induces differentiation of the fungal pathogen Histoplasma capsulatum into a pathogenic state characterized by infection of host phagocytes.
29295913	3	93	theme	pathogenic	526:535	arg1	cells					543:547	the pathogenic yeast cells	522:547	the pathogenic yeast cells but not those of avirulent mycelia	522:582	Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.
29295913	9	94	theme	core	1463:1466	arg1	temperature					1473:1483	the normal core body temperature	1452:1483	the normal core body temperature of mice	1452:1491	Treatment of mice with cyclophosphamide reduces the normal core body temperature of mice, and this decrease is sufficient to restore the infectivity of O-mannosylation-deficient yeast cells.
29295913	4	95	theme	Pmt2	672:675	arg1	mannosyltransferases					685:704	the Pmt1 and Pmt2 protein mannosyltransferases	659:704	mannosyltransferases	685:704	Histoplasma yeast cells lacking the Pmt1 and Pmt2 protein mannosyltransferases, which catalyze O-linked mannosylation of proteins, are severely attenuated during infection of mammalian hosts.
29295913	3	96	gly	glycosylation	448:460	arg1	proteins					479:486	extracellular proteins	465:486	extracellular proteins	465:486	Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection.
31181726	2	0	theme	containing-linked	415:431	arg1	macrocyclization					433:448	carbonate containing-linked macrocyclization	405:448	carbonate containing-linked macrocyclization	405:448	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	1	1	theme	drug-resistant	284:297	arg1	lines					311:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	1	2	link	7,9-O-linked	89:100	arg1	taxoids					114:120	novel 7,9-O-linked macrocyclic taxoids	83:120	novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position	83:166	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	3	3	theme	T7	787:788	arg1	region					795:800	the T7 loop region	783:800	the T7 loop region of βIII	783:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	1	4	from	position	159:166	arg1	modification					136:147	modification	136:147	modification at the C2 position	136:166	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	2	5	theme	carbonate	405:413	arg1	macrocyclization					433:448	carbonate containing-linked macrocyclization	405:448	carbonate containing-linked macrocyclization	405:448	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	1	6	theme	cancer	299:304	arg1	lines					311:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	2	7	theme	five-atom	618:626	arg1	linker					628:633	a five-atom linker	616:633	a five-atom linker	616:633	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	3	8	theme	loop	790:793	arg1	region					795:800	the T7 loop region	783:800	the T7 loop region of βIII	783:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	1	9	gly	P-glycoprotein	238:251	arg1	P-glycoprotein					238:251	P-glycoprotein	238:251	P-glycoprotein	238:251	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	3	10	from	interactions	765:776	arg1	cytotoxicity					713:724	the improved cytotoxicity	700:724	the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII	700:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	1	11	theme	cell	306:309	arg1	lines					311:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	2	12	theme	C-seco	357:362	arg1	taxoids					364:370	C-seco taxoids	357:370	C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization	357:448	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	2	13	link	containing-linked	415:431	arg1	macrocyclization					433:448	carbonate containing-linked macrocyclization	405:448	carbonate containing-linked macrocyclization	405:448	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	3	14	with	interactions	765:776	arg1	region					795:800	the T7 loop region	783:800	the T7 loop region of βIII	783:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	2	15	theme	drug-resistant	484:497	arg1	tumors					499:504	drug-resistant tumors	484:504	drug-resistant tumors	484:504	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	3	16	theme	βIII	805:808	arg1	region					795:800	the T7 loop region	783:800	the T7 loop region of βIII	783:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	1	17	theme	novel	83:87	arg1	taxoids					114:120	novel 7,9-O-linked macrocyclic taxoids	83:120	novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position	83:166	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	1	18	theme	7,9-O-linked	89:100	arg1	taxoids					114:120	novel 7,9-O-linked macrocyclic taxoids	83:120	novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position	83:166	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	2	19	theme	increased	458:466	arg1	cytotoxicity					468:479	increased cytotoxicity	458:479	increased cytotoxicity	458:479	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	1	20	theme	macrocyclic	102:112	arg1	taxoids					114:120	novel 7,9-O-linked macrocyclic taxoids	83:120	novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position	83:166	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	1	21	theme	taxoids	114:120	arg1	series					73:78	A series	71:78	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position	71:166	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	0	22	theme	Macrocyclic	43:53	arg1	C-Seco					55:60	7,9-O-Linked Macrocyclic C-Seco	30:60	7,9-O-Linked Macrocyclic C-Seco	30:60	Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids.
31181726	3	23	theme	enhanced	746:753	arg1	interactions					765:776	enhanced favorable interactions	746:776	enhanced favorable interactions with the T7 loop region of βIII	746:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	1	24	theme	drug-sensitive	219:232	arg1	lines					311:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	0	25	theme	7,9-O-Linked	30:41	arg1	C-Seco					55:60	7,9-O-Linked Macrocyclic C-Seco	30:60	7,9-O-Linked Macrocyclic C-Seco	30:60	Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids.
31181726	3	26	theme	22b	729:731	arg1	results					733:739	22b results	729:739	22b results	729:739	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	2	27	theme	compound	553:560	arg1	22b					562:564	compound 22b	553:564	compound 22b	553:564	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	2	27	theme	compound	553:560	arg1	potent					663:668	potent	663:668	potent	663:668	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	3	28	theme	results	733:739	arg1	cytotoxicity					713:724	the improved cytotoxicity	700:724	the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII	700:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	0	29	theme	C-Seco	55:60	arg1	Cytotoxicity					14:25	Cytotoxicity	14:25	Cytotoxicity	14:25	Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids.
31181726	0	29	theme	C-Seco	55:60	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis	0:8	Synthesis and Cytotoxicity of 7,9-O-Linked Macrocyclic C-Seco Taxoids.
31181726	3	30	theme	Molecular	671:679	arg1	modeling					681:688	Molecular modeling	671:688	Molecular modeling	671:688	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	3	31	theme	favorable	755:763	arg1	interactions					765:776	enhanced favorable interactions	746:776	enhanced favorable interactions with the T7 loop region of βIII	746:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	2	32	theme	2-m-methoxybenzoyl	577:594	arg1	group					596:600	a 2-m-methoxybenzoyl group	575:600	a 2-m-methoxybenzoyl group together with a five-atom linker	575:633	It is demonstrated that C-seco taxoids conformationally constrained via carbonate containing-linked macrocyclization display increased cytotoxicity on drug-resistant tumors overexpressing both βIII and P-gp, among which compound 22b, bearing a 2-m-methoxybenzoyl group together with a five-atom linker, was identified as the most potent.
31181726	3	33	theme	improved	704:711	arg1	cytotoxicity					713:724	the improved cytotoxicity	700:724	the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII	700:808	Molecular modeling suggested the improved cytotoxicity of 22b results from enhanced favorable interactions with the T7 loop region of βIII.
31181726	1	34	theme	C2	156:157	arg1	position					159:166	the C2 position	152:166	the C2 position	152:166	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31181726	1	35	theme	overexpressed	270:282	arg1	lines					311:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines	219:315	A series of novel 7,9-O-linked macrocyclic taxoids together with modification at the C2 position were synthesized, and their cytotoxicities against drug-sensitive and P-glycoprotein and βIII-tubulin overexpressed drug-resistant cancer cell lines were evaluated.
31484299	11	0	theme	biochemical	1389:1399	arg1	composition					1401:1411	a balanced biochemical composition	1378:1411	a balanced biochemical composition of macronutrients	1378:1429	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	10	1	theme	in	1317:1318	arg1	assays					1326:1331	several in vitro assays	1309:1331	several in vitro assays	1309:1331	The biomass showed moderate antioxidant activity in several in vitro assays.
31484299	2	2	theme	microalgal	160:169	arg1	biomass					171:177	microalgal biomass	160:177	microalgal biomass	160:177	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	3	3	theme	industrial	326:335	arg1	strains					337:343	industrial strains	326:343	industrial strains cultivated in an industrial setting	326:379	Although it is common to publish nutritional data for microalgae grown at the lab-scale, data about industrial strains cultivated in an industrial setting are scarce in the literature.
31484299	2	4	theme	Commercial	135:144	arg1	production					146:155	Commercial production	135:155	Commercial production of microalgal biomass for food and feed	135:195	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	2	4	theme	Commercial	135:144	arg1	trend					219:223	a recent worldwide trend	200:223	a recent worldwide trend	200:223	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	8	5	located	found	1101:1105	arg2	levels					976:981	Significant levels	964:981	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g)	964:1089	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	8	5	located	found	1101:1105	arg1	biomass					1114:1120	the biomass	1110:1120	the biomass	1110:1120	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	7	6	theme	amino	885:889	arg1	acids					891:895	essential amino acids	875:895	essential amino acids	875:895	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	8	7	theme	Significant	964:974	arg1	levels					976:981	Significant levels	964:981	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g)	964:1089	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	10	8	theme	several	1309:1315	arg1	assays					1326:1331	several in vitro assays	1309:1331	several in vitro assays	1309:1331	The biomass showed moderate antioxidant activity in several in vitro assays.
31484299	3	9	theme	industrial	362:371	arg1	setting					373:379	an industrial setting	359:379	an industrial setting	359:379	Although it is common to publish nutritional data for microalgae grown at the lab-scale, data about industrial strains cultivated in an industrial setting are scarce in the literature.
31484299	4	10	theme	sp	527:528	arg1	composition					449:459	the nutritional composition	433:459	the nutritional composition	433:459	Thus, here we present the nutritional composition and a microbiological and toxicological evaluation of Tetraselmis sp.
31484299	4	10	theme	sp	527:528	arg1	evaluation					501:510	a microbiological and toxicological evaluation	465:510	a microbiological and toxicological evaluation of Tetraselmis sp	465:528	Thus, here we present the nutritional composition and a microbiological and toxicological evaluation of Tetraselmis sp.
31484299	7	11	theme	acids	891:895	arg1	polysaccharides					947:961	starch-like polysaccharides	935:961	starch-like polysaccharides	935:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	11	theme	acids	891:895	arg1	amount					865:870	a balanced amount	854:870	a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides	854:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	11	theme	acids	891:895	arg1	acids					924:928	n-3 polyunsaturated fatty acids	898:928	n-3 polyunsaturated fatty acids	898:928	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	11	theme	acids	891:895	arg1	acids					891:895	essential amino acids	875:895	essential amino acids	875:895	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	12	theme	n-3	898:900	arg1	acids					924:928	n-3 polyunsaturated fatty acids	898:928	n-3 polyunsaturated fatty acids	898:928	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	9	13	theme	heavy	1156:1160	arg1	metals					1162:1167	heavy metals	1156:1167	heavy metals	1156:1167	Conversely, pathogenic bacteria, heavy metals, cyanotoxins, mycotoxins, polycyclic aromatic hydrocarbons, and pesticides were absent.
31484299	7	14	theme	polyunsaturated	902:916	arg1	acids					924:928	n-3 polyunsaturated fatty acids	898:928	n-3 polyunsaturated fatty acids	898:928	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	15	theme	starch-like	935:945	arg1	polysaccharides					947:961	starch-like polysaccharides	935:961	starch-like polysaccharides	935:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	11	16	theme	balanced	1380:1387	arg1	composition					1401:1411	a balanced biochemical composition	1378:1411	a balanced biochemical composition of macronutrients	1378:1429	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	1	17	theme	CTP4	70:73	arg1	Biomass					86:92	CTP4 Microalgal Biomass	70:92	CTP4 Microalgal Biomass	70:92	CTP4 Microalgal Biomass Produced in Industrial Photobioreactors.
31484299	4	18	theme	microbiological	467:481	arg1	evaluation					501:510	a microbiological and toxicological evaluation	465:510	a microbiological and toxicological evaluation of Tetraselmis sp	465:528	Thus, here we present the nutritional composition and a microbiological and toxicological evaluation of Tetraselmis sp.
31484299	3	19	theme	nutritional	259:269	arg1	data					271:274	nutritional data	259:274	nutritional data for microalgae grown at the lab-scale	259:312	Although it is common to publish nutritional data for microalgae grown at the lab-scale, data about industrial strains cultivated in an industrial setting are scarce in the literature.
31484299	7	20	theme	essential	875:883	arg1	acids					891:895	essential amino acids	875:895	essential amino acids	875:895	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	1	21	theme	Microalgal	75:84	arg1	Biomass					86:92	CTP4 Microalgal Biomass	70:92	CTP4 Microalgal Biomass	70:92	CTP4 Microalgal Biomass Produced in Industrial Photobioreactors.
31484299	11	22	dep	vitamins	1441:1448	arg1	pro-					1436:1439	pro-	1436:1439	pro-	1436:1439	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	2	23	theme	biomass	171:177	arg1	production					146:155	Commercial production	135:155	Commercial production of microalgal biomass for food and feed	135:195	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	2	23	theme	biomass	171:177	arg1	trend					219:223	a recent worldwide trend	200:223	a recent worldwide trend	200:223	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	7	24	theme	balanced	856:863	arg1	polysaccharides					947:961	starch-like polysaccharides	935:961	starch-like polysaccharides	935:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	24	theme	balanced	856:863	arg1	amount					865:870	a balanced amount	854:870	a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides	854:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	24	theme	balanced	856:863	arg1	acids					924:928	n-3 polyunsaturated fatty acids	898:928	n-3 polyunsaturated fatty acids	898:928	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	24	theme	balanced	856:863	arg1	acids					891:895	essential amino acids	875:895	essential amino acids	875:895	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	8	25	theme	79.2	1061:1064	arg1	mg					1066:1067	mg	1066:1067	mg	1066:1067	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	6	26	theme	dietary	697:703	arg1	g					724:724	24.6 g/100 g	713:724	24.6 g/100 g	713:724	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	26	theme	dietary	697:703	arg1	fibres					705:710	dietary fibres	697:710	dietary fibres (24.6 g/100 g)	697:725	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	7	27	theme	polysaccharides	947:961	arg1	polysaccharides					947:961	starch-like polysaccharides	935:961	starch-like polysaccharides	935:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	27	theme	polysaccharides	947:961	arg1	amount					865:870	a balanced amount	854:870	a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides	854:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	27	theme	polysaccharides	947:961	arg1	acids					924:928	n-3 polyunsaturated fatty acids	898:928	n-3 polyunsaturated fatty acids	898:928	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	27	theme	polysaccharides	947:961	arg1	acids					891:895	essential amino acids	875:895	essential amino acids	875:895	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	8	28	theme	mg	1066:1067	arg1	acid					1078:1081	79.2 mg ascorbic acid	1061:1081	79.2 mg ascorbic acid	1061:1081	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	4	29	theme	toxicological	487:499	arg1	evaluation					501:510	a microbiological and toxicological evaluation	465:510	a microbiological and toxicological evaluation of Tetraselmis sp	465:528	Thus, here we present the nutritional composition and a microbiological and toxicological evaluation of Tetraselmis sp.
31484299	5	30	theme	industrial	589:598	arg1	AlgaFarm					621:628	AlgaFarm	621:628	AlgaFarm	621:628	CTP4 biomass, cultivated in 100-m3 photobioreactors at an industrial production facility (AlgaFarm).
31484299	5	30	theme	industrial	589:598	arg1	facility					611:618	an industrial production facility	586:618	an industrial production facility (AlgaFarm)	586:629	CTP4 biomass, cultivated in 100-m3 photobioreactors at an industrial production facility (AlgaFarm).
31484299	3	31	from	scarce	385:390	arg1	literature					399:408	the literature	395:408	the literature	395:408	Although it is common to publish nutritional data for microalgae grown at the lab-scale, data about industrial strains cultivated in an industrial setting are scarce in the literature.
31484299	0	32	theme	Nutritional	0:10	arg1	Potential					12:20	Nutritional Potential	0:20	Nutritional Potential	0:20	Nutritional Potential and Toxicological Evaluation of Tetraselmis sp.
31484299	5	33	theme	production	600:609	arg1	AlgaFarm					621:628	AlgaFarm	621:628	AlgaFarm	621:628	CTP4 biomass, cultivated in 100-m3 photobioreactors at an industrial production facility (AlgaFarm).
31484299	5	33	theme	production	600:609	arg1	facility					611:618	an industrial production facility	586:618	an industrial production facility (AlgaFarm)	586:629	CTP4 biomass, cultivated in 100-m3 photobioreactors at an industrial production facility (AlgaFarm).
31484299	8	34	theme	chlorophyll	986:996	arg1	levels					976:981	Significant levels	964:981	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g)	964:1089	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	6	35	theme	lipid	802:806	arg1	g					828:828	7.04 g/100 g	817:828	7.04 g/100 g	817:828	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	35	theme	lipid	802:806	arg1	content					808:814	low lipid content	798:814	low lipid content (7.04 g/100 g)	798:829	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	0	36	theme	Toxicological	26:38	arg1	Evaluation					40:49	Toxicological Evaluation	26:49	Toxicological Evaluation	26:49	Nutritional Potential and Toxicological Evaluation of Tetraselmis sp.
31484299	11	37	theme	macronutrients	1416:1429	arg1	composition					1401:1411	a balanced biochemical composition	1378:1411	a balanced biochemical composition of macronutrients	1378:1429	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	11	37	theme	macronutrients	1416:1429	arg1	vitamins					1441:1448	(pro-)vitamins	1435:1448	(pro-)vitamins	1435:1448	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	11	38	used	used	1529:1532	arg2	strain					1515:1520	this strain	1510:1520	this strain	1510:1520	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	1	39	theme	Industrial	106:115	arg1	Photobioreactors					117:132	Industrial Photobioreactors	106:132	Industrial Photobioreactors	106:132	CTP4 Microalgal Biomass Produced in Industrial Photobioreactors.
31484299	11	40	theme	toxic	1463:1467	arg1	contaminants					1469:1480	any toxic contaminants	1459:1480	any toxic contaminants	1459:1480	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	8	41	theme	ascorbic	1069:1076	arg1	acid					1078:1081	79.2 mg ascorbic acid	1061:1081	79.2 mg ascorbic acid	1061:1081	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	9	42	theme	polycyclic	1195:1204	arg1	hydrocarbons					1215:1226	polycyclic aromatic hydrocarbons	1195:1226	polycyclic aromatic hydrocarbons	1195:1226	Conversely, pathogenic bacteria, heavy metals, cyanotoxins, mycotoxins, polycyclic aromatic hydrocarbons, and pesticides were absent.
31484299	7	43	theme	acids	924:928	arg1	polysaccharides					947:961	starch-like polysaccharides	935:961	starch-like polysaccharides	935:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	43	theme	acids	924:928	arg1	amount					865:870	a balanced amount	854:870	a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides	854:961	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	43	theme	acids	924:928	arg1	acids					924:928	n-3 polyunsaturated fatty acids	898:928	n-3 polyunsaturated fatty acids	898:928	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	7	43	theme	acids	924:928	arg1	acids					891:895	essential amino acids	875:895	essential amino acids	875:895	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	11	44	theme	nutritional	1538:1548	arg1	applications					1550:1561	nutritional applications	1538:1561	nutritional applications	1538:1561	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	9	45	theme	pathogenic	1135:1144	arg1	bacteria					1146:1153	pathogenic bacteria	1135:1153	pathogenic bacteria	1135:1153	Conversely, pathogenic bacteria, heavy metals, cyanotoxins, mycotoxins, polycyclic aromatic hydrocarbons, and pesticides were absent.
31484299	9	46	theme	aromatic	1206:1213	arg1	hydrocarbons					1215:1226	polycyclic aromatic hydrocarbons	1195:1226	polycyclic aromatic hydrocarbons	1195:1226	Conversely, pathogenic bacteria, heavy metals, cyanotoxins, mycotoxins, polycyclic aromatic hydrocarbons, and pesticides were absent.
31484299	4	47	theme	nutritional	437:447	arg1	composition					449:459	the nutritional composition	433:459	the nutritional composition	433:459	Thus, here we present the nutritional composition and a microbiological and toxicological evaluation of Tetraselmis sp.
31484299	6	48	theme	low	798:800	arg1	g					828:828	7.04 g/100 g	817:828	7.04 g/100 g	817:828	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	48	theme	low	798:800	arg1	content					808:814	low lipid content	798:814	low lipid content (7.04 g/100 g)	798:829	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	0	49	theme	sp	66:67	arg1	Potential					12:20	Nutritional Potential	0:20	Nutritional Potential	0:20	Nutritional Potential and Toxicological Evaluation of Tetraselmis sp.
31484299	0	49	theme	sp	66:67	arg1	Evaluation					40:49	Toxicological Evaluation	26:49	Toxicological Evaluation	26:49	Nutritional Potential and Toxicological Evaluation of Tetraselmis sp.
31484299	8	50	dep	acid	1078:1081	arg1	e.g.					1055:1058	e.g.	1055:1058	e.g.	1055:1058	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	11	51	contain	has	1374:1376	arg2	vitamins					1441:1448	(pro-)vitamins	1435:1448	(pro-)vitamins	1435:1448	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	11	51	contain	has	1374:1376	arg1	biomass					1357:1363	the biomass	1353:1363	the biomass produced	1353:1372	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	11	51	contain	has	1374:1376	arg2	composition					1401:1411	a balanced biochemical composition	1378:1411	a balanced biochemical composition of macronutrients	1378:1429	Taken together, as the biomass produced has a balanced biochemical composition of macronutrients and (pro-)vitamins, lacking any toxic contaminants, these results suggest that this strain can be used for nutritional applications.
31484299	5	52	theme	100-m3	559:564	arg1	photobioreactors					566:581	100-m3 photobioreactors	559:581	100-m3 photobioreactors	559:581	CTP4 biomass, cultivated in 100-m3 photobioreactors at an industrial production facility (AlgaFarm).
31484299	0	53	theme	Tetraselmis	54:64	arg1	sp					66:67	Tetraselmis sp	54:67	Tetraselmis sp	54:67	Nutritional Potential and Toxicological Evaluation of Tetraselmis sp.
31484299	8	54	theme	carotenoids	1013:1023	arg1	levels					976:981	Significant levels	964:981	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g)	964:1089	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
31484299	6	55	theme	digestible	728:737	arg1	g					765:765	18.1 g/100 g	754:765	18.1 g/100 g	754:765	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	55	theme	digestible	728:737	arg1	carbohydrates					739:751	digestible carbohydrates	728:751	digestible carbohydrates (18.1 g/100 g)	728:766	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	g					828:828	7.04 g/100 g	817:828	7.04 g/100 g	817:828	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg1	microalga					637:645	This microalga	632:645	This microalga	632:645	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	g					693:693	31.2 g/100 g	682:693	31.2 g/100 g	682:693	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	content					808:814	low lipid content	798:814	low lipid content (7.04 g/100 g)	798:829	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	protein					673:679	protein	673:679	protein	673:679	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	g					724:724	24.6 g/100 g	713:724	24.6 g/100 g	713:724	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	fibres					705:710	dietary fibres	697:710	dietary fibres (24.6 g/100 g)	697:725	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	g					765:765	18.1 g/100 g	754:765	18.1 g/100 g	754:765	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	carbohydrates					739:751	digestible carbohydrates	728:751	digestible carbohydrates (18.1 g/100 g)	728:766	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	56	contain	contained	647:655	arg2	amounts					662:668	high amounts	657:668	high amounts of protein (31.2 g/100 g)	657:694	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	10	57	theme	antioxidant	1285:1295	arg1	activity					1297:1304	moderate antioxidant activity	1276:1304	moderate antioxidant activity	1276:1304	The biomass showed moderate antioxidant activity in several in vitro assays.
31484299	6	58	theme	protein	673:679	arg1	g					693:693	31.2 g/100 g	682:693	31.2 g/100 g	682:693	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	58	theme	protein	673:679	arg1	protein					673:679	protein	673:679	protein	673:679	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	58	theme	protein	673:679	arg1	amounts					662:668	high amounts	657:668	high amounts of protein (31.2 g/100 g)	657:694	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	2	59	theme	worldwide	209:217	arg1	production					146:155	Commercial production	135:155	Commercial production of microalgal biomass for food and feed	135:195	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	2	59	theme	worldwide	209:217	arg1	trend					219:223	a recent worldwide trend	200:223	a recent worldwide trend	200:223	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	5	60	theme	CTP4	531:534	arg1	biomass					536:542	CTP4 biomass	531:542	CTP4 biomass	531:542	CTP4 biomass, cultivated in 100-m3 photobioreactors at an industrial production facility (AlgaFarm).
31484299	2	61	theme	recent	202:207	arg1	production					146:155	Commercial production	135:155	Commercial production of microalgal biomass for food and feed	135:195	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	2	61	theme	recent	202:207	arg1	trend					219:223	a recent worldwide trend	200:223	a recent worldwide trend	200:223	Commercial production of microalgal biomass for food and feed is a recent worldwide trend.
31484299	7	62	theme	fatty	918:922	arg1	acids					924:928	n-3 polyunsaturated fatty acids	898:928	n-3 polyunsaturated fatty acids	898:928	The biomass displayed a balanced amount of essential amino acids, n-3 polyunsaturated fatty acids, and starch-like polysaccharides.
31484299	10	63	dep	in	1317:1318	arg1	vitro					1320:1324	vitro	1320:1324	vitro	1320:1324	The biomass showed moderate antioxidant activity in several in vitro assays.
31484299	4	64	theme	Tetraselmis	515:525	arg1	sp					527:528	Tetraselmis sp	515:528	Tetraselmis sp	515:528	Thus, here we present the nutritional composition and a microbiological and toxicological evaluation of Tetraselmis sp.
31484299	10	65	theme	moderate	1276:1283	arg1	activity					1297:1304	moderate antioxidant activity	1276:1304	moderate antioxidant activity	1276:1304	The biomass showed moderate antioxidant activity in several in vitro assays.
31484299	6	66	theme	high	657:660	arg1	g					693:693	31.2 g/100 g	682:693	31.2 g/100 g	682:693	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	66	theme	high	657:660	arg1	protein					673:679	protein	673:679	protein	673:679	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	6	66	theme	high	657:660	arg1	amounts					662:668	high amounts	657:668	high amounts of protein (31.2 g/100 g)	657:694	This microalga contained high amounts of protein (31.2 g/100 g), dietary fibres (24.6 g/100 g), digestible carbohydrates (18.1 g/100 g) and ashes (15.2 g/100 g), but low lipid content (7.04 g/100 g).
31484299	8	67	theme	vitamins	1045:1052	arg1	levels					976:981	Significant levels	964:981	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g)	964:1089	Significant levels of chlorophyll (3.5 g/100 g), carotenoids (0.61 g/100 g), and vitamins (e.g., 79.2 mg ascorbic acid /100 g) were also found in the biomass.
29628239	0	0	theme	comparative	78:88	arg1	study					90:94	A comparative study	76:94	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.	0:126	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	6	1	theme	plasticizers	931:942	arg1	effect					909:914	The significant effect	893:914	The significant effect of polyol type plasticizers on the different properties of mucilage edible films	893:995	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	6	1	theme	plasticizers	931:942	arg1	related					1001:1007	related	1001:1007	related	1001:1007	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	4	2	dep	3	709:709	arg1	to					706:707	to	706:707	to	706:707	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	6	3	theme	polyol	919:924	arg1	plasticizers					931:942	polyol type plasticizers	919:942	polyol type plasticizers	919:942	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	6	4	with	interactions	1061:1072	arg1	polysaccharides					1088:1102	mucilage polysaccharides	1079:1102	mucilage polysaccharides	1079:1102	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	1	5	theme	Opuntia	171:177	arg1	Cactaceae					202:210	Cactaceae	202:210	Cactaceae	202:210	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
29628239	1	5	theme	Opuntia	171:177	arg1	cladodes					192:199	Opuntia ficus-indica cladodes	171:199	Opuntia ficus-indica cladodes (Cactaceae)	171:211	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
29628239	0	6	from	Development	0:10	arg1	mucilage					66:73	Opuntia ficus-indica mucilage	45:73	Opuntia ficus-indica mucilage	45:73	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	3	7	theme	mechanical	480:489	arg1	properties					503:512	The physical, thermal, mechanical and barrier properties	457:512	The physical, thermal, mechanical and barrier properties of the obtained films	457:534	The physical, thermal, mechanical and barrier properties of the obtained films were investigated.
29628239	4	8	theme	mucilage	613:620	arg1	films					622:626	plasticized mucilage films	601:626	plasticized mucilage films	601:626	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	6	9	theme	significant	897:907	arg1	effect					909:914	The significant effect	893:914	The significant effect of polyol type plasticizers on the different properties of mucilage edible films	893:995	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	6	9	theme	significant	897:907	arg1	related					1001:1007	related	1001:1007	related	1001:1007	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	5	10	dep	times	838:842	arg1	higher					844:849	higher	844:849	higher	844:849	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	6	11	theme	type	926:929	arg1	plasticizers					931:942	polyol type plasticizers	919:942	polyol type plasticizers	919:942	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	0	12	theme	polyol	107:112	arg1	plasticizers					114:125	various polyol plasticizers	99:125	various polyol plasticizers	99:125	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	6	13	from	effect	909:914	arg1	properties					961:970	the different properties	947:970	the different properties of mucilage edible films	947:995	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	3	14	theme	thermal	471:477	arg1	properties					503:512	The physical, thermal, mechanical and barrier properties	457:512	The physical, thermal, mechanical and barrier properties of the obtained films	457:534	The physical, thermal, mechanical and barrier properties of the obtained films were investigated.
29628239	1	15	theme	ficus-indica	179:190	arg1	Cactaceae					202:210	Cactaceae	202:210	Cactaceae	202:210	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
29628239	1	15	theme	ficus-indica	179:190	arg1	cladodes					192:199	Opuntia ficus-indica cladodes	171:199	Opuntia ficus-indica cladodes (Cactaceae)	171:211	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
29628239	0	16	theme	various	99:105	arg1	plasticizers					114:125	various polyol plasticizers	99:125	various polyol plasticizers	99:125	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	4	17	theme	plasticized	601:611	arg1	films					622:626	plasticized mucilage films	601:626	plasticized mucilage films	601:626	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	6	18	theme	films	991:995	arg1	properties					961:970	the different properties	947:970	the different properties of mucilage edible films	947:995	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	4	19	theme	WVP	691:693	arg1	values					696:701	water vapor permeability (WVP) values	665:701	water vapor permeability (WVP) values up to 3 times lower than the other films	665:742	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	2	20	theme	extracted	368:376	arg1	mucilage					378:385	the extracted mucilage	364:385	the extracted mucilage	364:385	Films from the extracted mucilage were loaded at 40% (w/w) with glycerol, sorbitol, PEG 200 or PEG 400.
29628239	0	21	theme	edible	27:32	arg1	films					34:38	plasticized edible films	15:38	plasticized edible films from Opuntia ficus-indica mucilage	15:73	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	1	22	theme	structural	289:298	arg1	features					300:307	its structural features	285:307	its structural features	285:307	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
29628239	3	23	theme	barrier	495:501	arg1	properties					503:512	The physical, thermal, mechanical and barrier properties	457:512	The physical, thermal, mechanical and barrier properties of the obtained films	457:534	The physical, thermal, mechanical and barrier properties of the obtained films were investigated.
29628239	4	24	theme	barrier	579:585	arg1	properties					587:596	The highest water vapor barrier properties	555:596	The highest water vapor barrier properties of plasticized mucilage films	555:626	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	0	25	theme	plasticized	15:25	arg1	films					34:38	plasticized edible films	15:38	plasticized edible films from Opuntia ficus-indica mucilage	15:73	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	1	26	dep	1H	337:338	arg1	NMR					348:350	NMR	348:350	NMR	348:350	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
29628239	0	27	theme	plasticizers	114:125	arg1	study					90:94	A comparative study	76:94	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.	0:126	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	6	28	theme	thermal	1132:1138	arg1	properties					1140:1149	FTIR and thermal properties	1123:1149	FTIR and thermal properties	1123:1149	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	4	29	theme	vapor	573:577	arg1	properties					587:596	The highest water vapor barrier properties	555:596	The highest water vapor barrier properties of plasticized mucilage films	555:626	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	5	30	theme	glycerol-plasticized	865:884	arg1	films					886:890	glycerol-plasticized films	865:890	glycerol-plasticized films	865:890	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	6	31	theme	different	1051:1059	arg1	interactions					1061:1072	different interactions	1051:1072	different interactions with mucilage polysaccharides	1051:1102	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	4	32	theme	films	622:626	arg1	properties					587:596	The highest water vapor barrier properties	555:596	The highest water vapor barrier properties of plasticized mucilage films	555:626	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	0	33	theme	films	34:38	arg1	Development					0:10	Development	0:10	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.	0:126	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	5	34	theme	tensile	749:755	arg1	TS					767:768	TS	767:768	TS	767:768	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	5	34	theme	tensile	749:755	arg1	strength					757:764	tensile strength	749:764	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol	745:823	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	2	35	from	mucilage	378:385	arg1	Films					353:357	Films	353:357	Films from the extracted mucilage	353:385	Films from the extracted mucilage were loaded at 40% (w/w) with glycerol, sorbitol, PEG 200 or PEG 400.
29628239	6	36	theme	different	951:959	arg1	properties					961:970	the different properties	947:970	the different properties of mucilage edible films	947:995	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	0	37	theme	ficus-indica	53:64	arg1	mucilage					66:73	Opuntia ficus-indica mucilage	45:73	Opuntia ficus-indica mucilage	45:73	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	0	38	from	mucilage	66:73	arg1	Development					0:10	Development	0:10	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.	0:126	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	0	38	from	mucilage	66:73	arg1	films					34:38	plasticized edible films	15:38	plasticized edible films from Opuntia ficus-indica mucilage	15:73	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	3	39	theme	obtained	521:528	arg1	films					530:534	the obtained films	517:534	the obtained films	517:534	The physical, thermal, mechanical and barrier properties of the obtained films were investigated.
29628239	4	40	theme	highest	559:565	arg1	properties					587:596	The highest water vapor barrier properties	555:596	The highest water vapor barrier properties of plasticized mucilage films	555:626	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	4	41	theme	vapor	671:675	arg1	values					696:701	water vapor permeability (WVP) values	665:701	water vapor permeability (WVP) values up to 3 times lower than the other films	665:742	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	0	42	theme	Opuntia	45:51	arg1	mucilage					66:73	Opuntia ficus-indica mucilage	45:73	Opuntia ficus-indica mucilage	45:73	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	6	43	theme	FTIR	1123:1126	arg1	properties					1140:1149	FTIR and thermal properties	1123:1149	FTIR and thermal properties	1123:1149	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	6	44	theme	edible	984:989	arg1	films					991:995	mucilage edible films	975:995	mucilage edible films	975:995	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	3	45	theme	films	530:534	arg1	properties					503:512	The physical, thermal, mechanical and barrier properties	457:512	The physical, thermal, mechanical and barrier properties of the obtained films	457:534	The physical, thermal, mechanical and barrier properties of the obtained films were investigated.
29628239	4	46	theme	water	665:669	arg1	values					696:701	water vapor permeability (WVP) values	665:701	water vapor permeability (WVP) values up to 3 times lower than the other films	665:742	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	4	47	theme	other	732:736	arg1	films					738:742	the other films	728:742	the other films	728:742	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	1	48	theme	Mucilage	128:135	arg1	polysaccharide					137:150	Mucilage polysaccharide	128:150	Mucilage polysaccharide	128:150	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
29628239	6	49	theme	mucilage	1079:1086	arg1	polysaccharides					1088:1102	mucilage polysaccharides	1079:1102	mucilage polysaccharides	1079:1102	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	4	50	theme	lower	717:721	arg1	values					696:701	water vapor permeability (WVP) values	665:701	water vapor permeability (WVP) values up to 3 times lower than the other films	665:742	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	5	51	theme	strength	757:764	arg1	values					771:776	The tensile strength (TS) values	745:776	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol	745:823	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	5	51	theme	strength	757:764	arg1	times					838:842	times	838:842	times	838:842	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	4	52	theme	permeability	677:688	arg1	values					696:701	water vapor permeability (WVP) values	665:701	water vapor permeability (WVP) values up to 3 times lower than the other films	665:742	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	5	53	theme	2	836:836	arg1	values					771:776	The tensile strength (TS) values	745:776	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol	745:823	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	5	53	theme	2	836:836	arg1	times					838:842	times	838:842	times	838:842	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	6	54	theme	mucilage	975:982	arg1	films					991:995	mucilage edible films	975:995	mucilage edible films	975:995	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	3	55	theme	physical	461:468	arg1	properties					503:512	The physical, thermal, mechanical and barrier properties	457:512	The physical, thermal, mechanical and barrier properties of the obtained films	457:534	The physical, thermal, mechanical and barrier properties of the obtained films were investigated.
29628239	5	56	theme	films	781:785	arg1	values					771:776	The tensile strength (TS) values	745:776	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol	745:823	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	5	56	theme	films	781:785	arg1	times					838:842	times	838:842	times	838:842	The tensile strength (TS) values of films plasticized with PEG 200 and sorbitol were about 2 times higher than those of glycerol-plasticized films.
29628239	4	57	theme	water	567:571	arg1	properties					587:596	The highest water vapor barrier properties	555:596	The highest water vapor barrier properties of plasticized mucilage films	555:626	The highest water vapor barrier properties of plasticized mucilage films were obtained with sorbitol reaching water vapor permeability (WVP) values up to 3 times lower than the other films.
29628239	0	58	dep	Development	0:10	arg1	study					90:94	A comparative study	76:94	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.	0:126	Development of plasticized edible films from Opuntia ficus-indica mucilage: A comparative study of various polyol plasticizers.
29628239	6	59	theme	structural	1018:1027	arg1	features					1029:1036	their structural features	1012:1036	their structural features that promote different interactions with mucilage polysaccharides	1012:1102	The significant effect of polyol type plasticizers on the different properties of mucilage edible films was related to their structural features that promote different interactions with mucilage polysaccharides as demonstrated by FTIR and thermal properties.
29628239	1	60	theme	sugar	251:255	arg1	analysis					257:264	sugar analysis	251:264	sugar analysis using HPLC-RID	251:279	Mucilage polysaccharide was extracted from Opuntia ficus-indica cladodes (Cactaceae) and its composition was determined by sugar analysis using HPLC-RID and its structural features were elucidated by FTIR and 1H and 13C NMR.
30960688	7	0	theme	TOC	1393:1395	arg1	concentration					1397:1409	the TOC concentration	1389:1409	the TOC concentration of EPS	1389:1416	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	4	1	theme	carbon	646:651	arg1	results					659:665	The total organic carbon (TOC) results	628:665	The total organic carbon (TOC) results	628:665	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	2	2	dep	understand	280:289	arg1	to					277:278	to	277:278	to	277:278	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	1	3	theme	VOC	251:253	arg1	biofilters					256:265	volatile organic compound (VOC) biofilters	224:265	volatile organic compound (VOC) biofilters	224:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	4	4	theme	organic	638:644	arg1	TOC					654:656	TOC	654:656	TOC	654:656	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	4	4	theme	organic	638:644	arg1	carbon					646:651	total organic carbon	632:651	The total organic carbon (TOC) results	628:665	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	3	5	theme	treating	522:529	arg1	toluene					539:545	a biofilter treating gaseous toluene	510:545	a biofilter treating gaseous toluene	510:545	EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h.
30960688	6	6	theme	ozone	1104:1108	arg1	attack					1110:1115	ozone attack	1104:1115	ozone attack	1104:1115	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	3	7	from	ppm	601:603	arg1	ozone					583:587	gaseous ozone	575:587	gaseous ozone at 272 ± 22 ppm	575:603	EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h.
30960688	5	8	theme	specific	907:914	arg1	residues					927:934	specific amino acid residues	907:934	specific amino acid residues (such as tryptophan)	907:955	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	3	9	theme	gaseous	531:537	arg1	toluene					539:545	a biofilter treating gaseous toluene	510:545	a biofilter treating gaseous toluene	510:545	EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h.
30960688	5	10	dep	attack	879:884	arg1	ring					898:901	the benzene ring	886:901	the benzene ring	886:901	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	5	11	theme	matrix	795:800	arg1	EEM					829:831	EEM	829:831	EEM	829:831	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	5	11	theme	matrix	795:800	arg1	spectroscopy					815:826	The excitation-emission matrix fluorescence spectroscopy	771:826	The excitation-emission matrix fluorescence spectroscopy (EEM) results	771:840	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	0	12	theme	Gaseous	111:117	arg1	Toluene					119:125	Gaseous Toluene	111:125	Gaseous Toluene	111:125	Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
30960688	7	13	theme	minor	1373:1377	arg1	change					1379:1384	a minor change	1371:1384	a minor change in the TOC concentration of EPS	1371:1416	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	5	14	theme	amino	916:920	arg1	residues					927:934	specific amino acid residues	907:934	specific amino acid residues (such as tryptophan)	907:955	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	5	15	theme	spectroscopy	815:826	arg1	results					834:840	The excitation-emission matrix fluorescence spectroscopy (EEM) results	771:840	The excitation-emission matrix fluorescence spectroscopy (EEM) results	771:840	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	1	16	theme	novel	175:179	arg1	ozonation					146:154	Low-concentration ozonation	128:154	Low-concentration ozonation	128:154	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	1	16	theme	novel	175:179	arg1	technique					181:189	a novel technique	173:189	a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters	173:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	8	17	theme	key	1529:1531	arg1	EPS					1510:1512	biofilter EPS	1500:1512	biofilter EPS which can be a key reason for controlling biomass accumulation	1500:1575	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	8	17	theme	key	1529:1531	arg1	reason					1533:1538	a key reason	1527:1538	a key reason for controlling biomass accumulation	1527:1575	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	8	18	theme	low	1441:1443	arg1	ozone					1459:1463	low concentration ozone	1441:1463	low concentration ozone	1441:1463	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	7	19	from	change	1379:1384	arg1	concentration					1397:1409	the TOC concentration	1389:1409	the TOC concentration of EPS	1389:1416	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	2	20	from	changes	345:351	arg1	properties					356:365	properties	356:365	properties of ozone exposed extracellular polymeric substances (EPS)	356:423	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	3	21	theme	biofilter	512:520	arg1	toluene					539:545	a biofilter treating gaseous toluene	510:545	a biofilter treating gaseous toluene	510:545	EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h.
30960688	5	22	from	residues	927:934	arg1	chain					972:976	the protein chain	960:976	the protein chain	960:976	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	2	23	theme	exposed	376:382	arg1	substances					408:417	ozone exposed extracellular polymeric substances	370:417	ozone exposed extracellular polymeric substances (EPS)	370:423	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	2	23	theme	exposed	376:382	arg1	EPS					420:422	EPS	420:422	EPS	420:422	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	7	24	theme	organic	1227:1233	arg1	VOCs					1246:1249	VOCs	1246:1249	VOCs	1246:1249	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	24	theme	organic	1227:1233	arg1	compounds					1235:1243	few volatile organic compounds	1214:1243	few volatile organic compounds (VOCs)	1214:1250	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	24	theme	organic	1227:1233	arg1	acids					1272:1276	carboxylic acids	1261:1276	carboxylic acids	1261:1276	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	5	25	theme	benzene	890:896	arg1	ring					898:901	the benzene ring	886:901	the benzene ring	886:901	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	6	26	theme	size-exclusion	996:1009	arg1	HPSEC					1027:1031	HPSEC	1027:1031	HPSEC	1027:1031	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	6	26	theme	size-exclusion	996:1009	arg1	chromatography					1011:1024	High performance size-exclusion chromatography	979:1024	High performance size-exclusion chromatography (HPSEC) results	979:1040	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	2	27	theme	ozone	370:374	arg1	substances					408:417	ozone exposed extracellular polymeric substances	370:417	ozone exposed extracellular polymeric substances (EPS)	370:423	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	2	27	theme	ozone	370:374	arg1	EPS					420:422	EPS	420:422	EPS	420:422	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	7	28	theme	EPS	1414:1416	arg1	concentration					1397:1409	the TOC concentration	1389:1409	the TOC concentration of EPS	1389:1416	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	6	29	theme	performance	984:994	arg1	HPSEC					1027:1031	HPSEC	1027:1031	HPSEC	1027:1031	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	6	29	theme	performance	984:994	arg1	chromatography					1011:1024	High performance size-exclusion chromatography	979:1024	High performance size-exclusion chromatography (HPSEC) results	979:1040	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	4	30	theme	carbon	738:743	arg1	CO₂					754:756	CO₂	754:756	CO₂	754:756	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	4	30	theme	carbon	738:743	arg1	dioxide					745:751	carbon dioxide	738:751	carbon dioxide (CO₂)	738:757	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	2	31	theme	reaction	295:302	arg1	mechanism					304:312	the reaction mechanism	291:312	the reaction mechanism between ozone and biomass	291:338	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	6	32	theme	chromatography	1011:1024	arg1	results					1034:1040	High performance size-exclusion chromatography (HPSEC) results	979:1040	High performance size-exclusion chromatography (HPSEC) results	979:1040	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	6	33	theme	High	979:982	arg1	HPSEC					1027:1031	HPSEC	1027:1031	HPSEC	1027:1031	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	6	33	theme	High	979:982	arg1	chromatography					1011:1024	High performance size-exclusion chromatography	979:1024	High performance size-exclusion chromatography (HPSEC) results	979:1040	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	7	34	theme	toluene	1331:1337	arg1	acids					1272:1276	carboxylic acids	1261:1276	carboxylic acids	1261:1276	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	34	theme	toluene	1331:1337	arg1	ketones					1290:1296	ketones	1290:1296	ketones	1290:1296	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	34	theme	toluene	1331:1337	arg1	aldehydes					1279:1287	aldehydes	1279:1287	aldehydes	1279:1287	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	34	theme	toluene	1331:1337	arg1	by-products					1316:1326	by-products	1316:1326	by-products	1316:1326	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	34	theme	toluene	1331:1337	arg1	benzaldehyde					1299:1310	benzaldehyde	1299:1310	benzaldehyde	1299:1310	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	4	35	theme	low	682:684	arg1	ozone					700:704	low concentration ozone	682:704	low concentration ozone	682:704	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	1	36	theme	excess	206:211	arg1	biomass					213:219	the excess biomass	202:219	the excess biomass in volatile organic compound (VOC) biofilters	202:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	0	37	theme	Polymeric	48:56	arg1	EPS					70:72	EPS	70:72	EPS	70:72	Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
30960688	0	37	theme	Polymeric	48:56	arg1	Substances					58:67	Extracellular Polymeric Substances	34:67	Extracellular Polymeric Substances (EPS)	34:73	Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
30960688	7	38	theme	volatile	1218:1225	arg1	VOCs					1246:1249	VOCs	1246:1249	VOCs	1246:1249	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	38	theme	volatile	1218:1225	arg1	compounds					1235:1243	few volatile organic compounds	1214:1243	few volatile organic compounds (VOCs)	1214:1250	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	38	theme	volatile	1218:1225	arg1	acids					1272:1276	carboxylic acids	1261:1276	carboxylic acids	1261:1276	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	5	39	dep	residues	927:934	arg1	such					937:940	such	937:940	such	937:940	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	8	40	theme	biomass	1556:1562	arg1	accumulation					1564:1575	biomass accumulation	1556:1575	biomass accumulation	1556:1575	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	2	41	theme	substances	408:417	arg1	properties					356:365	properties	356:365	properties of ozone exposed extracellular polymeric substances (EPS)	356:423	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	2	42	theme	extracellular	384:396	arg1	substances					408:417	ozone exposed extracellular polymeric substances	370:417	ozone exposed extracellular polymeric substances (EPS)	370:423	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	2	42	theme	extracellular	384:396	arg1	EPS					420:422	EPS	420:422	EPS	420:422	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	8	43	theme	molecular	1480:1488	arg1	weight					1490:1495	the molecular weight	1476:1495	the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation	1476:1575	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	0	44	theme	Extracellular	34:46	arg1	EPS					70:72	EPS	70:72	EPS	70:72	Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
30960688	0	44	theme	Extracellular	34:46	arg1	Substances					58:67	Extracellular Polymeric Substances	34:67	Extracellular Polymeric Substances (EPS)	34:73	Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
30960688	1	45	from	biomass	213:219	arg1	biofilters					256:265	volatile organic compound (VOC) biofilters	224:265	volatile organic compound (VOC) biofilters	224:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	2	46	theme	polymeric	398:406	arg1	substances					408:417	ozone exposed extracellular polymeric substances	370:417	ozone exposed extracellular polymeric substances (EPS)	370:423	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	2	46	theme	polymeric	398:406	arg1	EPS					420:422	EPS	420:422	EPS	420:422	In order to understand the reaction mechanism between ozone and biomass, the changes in properties of ozone exposed extracellular polymeric substances (EPS) were investigated in this study.
30960688	8	47	theme	biofilter	1500:1508	arg1	EPS					1510:1512	biofilter EPS	1500:1512	biofilter EPS which can be a key reason for controlling biomass accumulation	1500:1575	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	8	47	theme	biofilter	1500:1508	arg1	reason					1533:1538	a key reason	1527:1538	a key reason for controlling biomass accumulation	1527:1575	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	7	48	theme	carboxylic	1261:1270	arg1	ketones					1290:1296	ketones	1290:1296	ketones	1290:1296	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	48	theme	carboxylic	1261:1270	arg1	by-products					1316:1326	by-products	1316:1326	by-products	1316:1326	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	48	theme	carboxylic	1261:1270	arg1	aldehydes					1279:1287	aldehydes	1279:1287	aldehydes	1279:1287	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	48	theme	carboxylic	1261:1270	arg1	acids					1272:1276	carboxylic acids	1261:1276	carboxylic acids	1261:1276	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	48	theme	carboxylic	1261:1270	arg1	benzaldehyde					1299:1310	benzaldehyde	1299:1310	benzaldehyde	1299:1310	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	3	49	theme	22	598:599	arg1	±					596:596	±	596:596	±	596:596	EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h.
30960688	7	50	theme	few	1214:1216	arg1	VOCs					1246:1249	VOCs	1246:1249	VOCs	1246:1249	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	50	theme	few	1214:1216	arg1	compounds					1235:1243	few volatile organic compounds	1214:1243	few volatile organic compounds (VOCs)	1214:1250	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	7	50	theme	few	1214:1216	arg1	acids					1272:1276	carboxylic acids	1261:1276	carboxylic acids	1261:1276	During ozonation, few volatile organic compounds (VOCs), such as carboxylic acids, aldehydes, ketones, benzaldehyde and by-products of toluene, were generated, which confirms a minor change in the TOC concentration of EPS.
30960688	0	51	theme	Substances	58:67	arg1	Depolymerization					14:29	Depolymerization	14:29	Depolymerization	14:29	Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
30960688	0	51	theme	Substances	58:67	arg1	Ozonation					0:8	Ozonation	0:8	Ozonation	0:8	Ozonation and Depolymerization of Extracellular Polymeric Substances (EPS) Extracted from a Biofilter Treating Gaseous Toluene.
30960688	9	52	from	composition	1622:1632	arg1	biofilters					1654:1663	biofilters	1654:1663	biofilters	1654:1663	Additionally, this can be used to study the composition of biofilm EPS from biofilters.
30960688	5	53	theme	protein	964:970	arg1	chain					972:976	the protein chain	960:976	the protein chain	960:976	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	9	54	from	biofilters	1654:1663	arg1	composition					1622:1632	the composition	1618:1632	the composition of biofilm EPS from biofilters	1618:1663	Additionally, this can be used to study the composition of biofilm EPS from biofilters.
30960688	9	54	from	biofilters	1654:1663	arg1	EPS					1645:1647	biofilm EPS	1637:1647	biofilm EPS from biofilters	1637:1663	Additionally, this can be used to study the composition of biofilm EPS from biofilters.
30960688	6	55	theme	protein	1061:1067	arg1	molecules					1069:1077	the protein molecules	1057:1077	the protein molecules	1057:1077	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	9	56	used	used	1604:1607	arg2	this					1592:1595	this	1592:1595	this	1592:1595	Additionally, this can be used to study the composition of biofilm EPS from biofilters.
30960688	6	57	theme	polysaccharides	1148:1162	arg1	weight					1138:1143	the molecular weight	1124:1143	the molecular weight of polysaccharides	1124:1162	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	1	58	theme	Low-concentration	128:144	arg1	ozonation					146:154	Low-concentration ozonation	128:154	Low-concentration ozonation	128:154	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	1	58	theme	Low-concentration	128:144	arg1	technique					181:189	a novel technique	173:189	a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters	173:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	4	59	theme	concentration	686:698	arg1	ozone					700:704	low concentration ozone	682:704	low concentration ozone	682:704	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	1	60	theme	volatile	224:231	arg1	biofilters					256:265	volatile organic compound (VOC) biofilters	224:265	volatile organic compound (VOC) biofilters	224:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	5	61	theme	acid	922:925	arg1	residues					927:934	specific amino acid residues	907:934	specific amino acid residues (such as tryptophan)	907:955	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	3	62	theme	272	592:594	arg1	±					596:596	±	596:596	±	596:596	EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h.
30960688	5	63	from	attack	879:884	arg1	chain					972:976	the protein chain	960:976	the protein chain	960:976	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	1	64	theme	organic	233:239	arg1	biofilters					256:265	volatile organic compound (VOC) biofilters	224:265	volatile organic compound (VOC) biofilters	224:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	9	65	theme	biofilm	1637:1643	arg1	EPS					1645:1647	biofilm EPS	1637:1647	biofilm EPS from biofilters	1637:1663	Additionally, this can be used to study the composition of biofilm EPS from biofilters.
30960688	5	66	theme	excitation-emission	775:793	arg1	EEM					829:831	EEM	829:831	EEM	829:831	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	5	66	theme	excitation-emission	775:793	arg1	spectroscopy					815:826	The excitation-emission matrix fluorescence spectroscopy	771:826	The excitation-emission matrix fluorescence spectroscopy (EEM) results	771:840	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	3	67	theme	gaseous	575:581	arg1	ozone					583:587	gaseous ozone	575:587	gaseous ozone at 272 ± 22 ppm	575:603	EPS was sequestered from the biofilm, obtained from a biofilter treating gaseous toluene, and then it was exposed to gaseous ozone at 272 ± 22 ppm continuously for 12 h.
30960688	8	68	theme	concentration	1445:1457	arg1	ozone					1459:1463	low concentration ozone	1441:1463	low concentration ozone	1441:1463	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
30960688	4	69	theme	total	632:636	arg1	TOC					654:656	TOC	654:656	TOC	654:656	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	4	69	theme	total	632:636	arg1	carbon					646:651	total organic carbon	632:651	The total organic carbon (TOC) results	628:665	The total organic carbon (TOC) results indicated that low concentration ozone could not mineralize the EPS to carbon dioxide (CO₂) completely.
30960688	5	70	theme	fluorescence	802:813	arg1	EEM					829:831	EEM	829:831	EEM	829:831	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	5	70	theme	fluorescence	802:813	arg1	spectroscopy					815:826	The excitation-emission matrix fluorescence spectroscopy	771:826	The excitation-emission matrix fluorescence spectroscopy (EEM) results	771:840	The excitation-emission matrix fluorescence spectroscopy (EEM) results demonstrated that ozone preferred to attack the benzene ring and specific amino acid residues (such as tryptophan) on the protein chain.
30960688	1	71	theme	compound	241:248	arg1	biofilters					256:265	volatile organic compound (VOC) biofilters	224:265	volatile organic compound (VOC) biofilters	224:265	Low-concentration ozonation was developed as a novel technique to control the excess biomass in volatile organic compound (VOC) biofilters.
30960688	9	72	theme	EPS	1645:1647	arg1	composition					1622:1632	the composition	1618:1632	the composition of biofilm EPS from biofilters	1618:1663	Additionally, this can be used to study the composition of biofilm EPS from biofilters.
30960688	6	73	theme	molecular	1128:1136	arg1	weight					1138:1143	the molecular weight	1124:1143	the molecular weight of polysaccharides	1124:1162	High performance size-exclusion chromatography (HPSEC) results confirmed that the protein molecules were depolymerized after ozone attack, while the molecular weight of polysaccharides was not much affected by ozone.
30960688	8	74	theme	EPS	1510:1512	arg1	weight					1490:1495	the molecular weight	1476:1495	the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation	1476:1575	Results revealed that low concentration ozone can reduce the molecular weight of biofilter EPS which can be a key reason for controlling biomass accumulation.
29772801	8	0	theme	current	928:934	arg1	algorithms					936:945	current algorithms	928:945	current algorithms	928:945	Most sites were unpredicted by current algorithms.
29772801	13	1	theme	molecular	1615:1623	arg1	pathway					1625:1631	a novel molecular pathway	1607:1631	a novel molecular pathway that may profoundly influence lamin A function	1607:1678	These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function.
29772801	9	2	theme	S612A/T643A	963:973	arg1	tails					984:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites.
29772801	9	3	theme	lamin	976:980	arg1	tails					984:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites.
29772801	7	4	from	sites	817:821	arg1	spot					835:838	a 'sweet spot'	826:839	a 'sweet spot' unique to lamin A	826:857	Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide.
29772801	14	5	dep	predictions	1789:1799	arg1	contribute					1823:1832	contribute	1823:1832	may contribute to disease by perturbing OGT-dependent regulation	1819:1882	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	14	5	dep	predictions	1789:1799	arg1	cause					1922:1926	cause	1922:1926	might cause OGT to misregulate wildtype lamin A	1916:1962	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	14	6	theme	lamin	1701:1705	arg1	A					1707:1707	lamin A	1701:1707	lamin A	1701:1707	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	12	7	theme	mouse	1531:1535	arg1	Tet1					1537:1540	mouse Tet1	1531:1540	mouse Tet1	1531:1540	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	14	8	theme	lamin	1956:1960	arg1	A					1962:1962	wildtype lamin A	1947:1962	wildtype lamin A	1947:1962	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	12	9	theme	O-GlcNAc	1409:1416	arg1	sites					1418:1422	identified O-GlcNAc sites	1398:1422	identified O-GlcNAc sites	1398:1422	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	7	10	dep	seven	871:875	arg1	to					868:869	to	868:869	to	868:869	Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide.
29772801	7	11	theme	sweet	829:833	arg1	spot					835:838	a 'sweet spot'	826:839	a 'sweet spot' unique to lamin A	826:857	Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide.
29772801	1	12	theme	gene	170:173	arg1	regulation					175:184	gene regulation	170:184	gene regulation	170:184	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	7	13	theme	lamin	851:855	arg1	A					857:857	lamin A	851:857	lamin A	851:857	Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide.
29772801	6	14	theme	tails	759:763	arg1	modification					704:715	no detectable modification	690:715	no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails	690:763	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	7	15	theme	unique	841:846	arg1	spot					835:838	a 'sweet spot'	826:839	a 'sweet spot' unique to lamin A	826:857	Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide.
29772801	5	16	theme	lamin	422:426	arg1	A					428:428	lamin A	422:428	lamin A	422:428	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	11	17	theme	substrate	1272:1280	arg1	recognition					1282:1292	substrate recognition	1272:1292	substrate recognition	1272:1292	We conclude that residues deleted in progeria are required for substrate recognition and/or modification by OGT in vitro.
29772801	1	18	from	roles	131:135	arg1	signaling					159:167	signaling	159:167	signaling	159:167	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	1	18	from	roles	131:135	arg1	regulation					175:184	gene regulation	170:184	gene regulation	170:184	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	1	18	from	roles	131:135	arg1	structure					148:156	nuclear structure	140:156	nuclear structure	140:156	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	1	18	from	roles	131:135	arg1	integrity					198:206	genome integrity	191:206	genome integrity	191:206	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	5	19	from	cells	509:513	arg1	-modified					474:482	-modified	474:482	-modified	474:482	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	1	20	theme	key	127:129	arg1	roles					131:135	key roles	127:135	key roles in nuclear structure, signaling, gene regulation, and genome integrity	127:206	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	6	21	with	assays	544:549	arg1	enzyme					592:597	purified O-GlcNAc transferase (OGT) enzyme	556:597	purified O-GlcNAc transferase (OGT) enzyme	556:597	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	12	22	dep	residues	1479:1486	arg1	622⁻625					1488:1494	622⁻625	1488:1494	622⁻625	1488:1494	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	12	22	dep	residues	1479:1486	arg1	639⁻645					1500:1506	639⁻645	1500:1506	639⁻645	1500:1506	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	1	23	dep	lamins	107:112	arg1	lamins					107:112	lamins A and C	107:120	lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity	107:206	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	1	23	dep	lamins	107:112	arg1	C					120:120	C	120:120	C	120:120	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	1	23	dep	lamins	107:112	arg1	A					114:114	A	114:114	A	114:114	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	14	24	theme	genetic	1802:1808	arg1	variants					1810:1817	genetic variants	1802:1817	genetic variants	1802:1817	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	13	25	theme	lamin	1663:1667	arg1	function					1671:1678	lamin A function	1663:1678	lamin A function	1663:1678	These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function.
29772801	5	26	theme	-modified	474:482	arg1	O-GlcNAc					465:472	O-GlcNAc	465:472	O-GlcNAc	465:472	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	5	26	theme	-modified	474:482	arg1	N-acetylglucosamine-					444:463	β-O-linked N-acetylglucosamine-	433:463	β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver	433:532	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	12	27	theme	lamin	1471:1475	arg1	motifs					1463:1468	potential OGT-association motifs	1437:1468	potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1	1437:1540	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	12	27	theme	lamin	1471:1475	arg1	residues					1479:1486	lamin A residues 622⁻625 and 639⁻645	1471:1506	lamin A residues 622⁻625 and 639⁻645	1471:1506	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	4	28	theme	distinct	391:398	arg1	roles					400:404	apparently distinct roles	380:404	apparently distinct roles	380:404	However, they form separate filaments in vivo, with apparently distinct roles.
29772801	5	29	theme	human	487:491	arg1	cells					509:513	human hepatoma (Huh7) cells	487:513	human hepatoma (Huh7) cells	487:513	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	6	30	theme	O-GlcNAc	565:572	arg1	OGT					587:589	OGT	587:589	OGT	587:589	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	30	theme	O-GlcNAc	565:572	arg1	transferase					574:584	O-GlcNAc transferase	565:584	purified O-GlcNAc transferase (OGT) enzyme	556:597	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	0	31	theme	O-GlcNAc	5:12	arg1	OGT					0:2	OGT	0:2	OGT (O-GlcNAc Transferase)	0:25	OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.
29772801	0	31	theme	O-GlcNAc	5:12	arg1	Transferase					14:24	O-GlcNAc Transferase	5:24	O-GlcNAc Transferase	5:24	OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.
29772801	6	32	theme	C	736:736	arg1	modification					704:715	no detectable modification	690:715	no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails	690:763	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	1	33	theme	LMNA	89:92	arg1	lamins					107:112	lamins A and C	107:120	lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity	107:206	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	1	33	theme	LMNA	89:92	arg1	gene					94:97	The LMNA gene	85:97	The LMNA gene	85:97	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	12	34	theme	potential	1437:1445	arg1	motifs					1463:1468	potential OGT-association motifs	1437:1468	potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1	1437:1540	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	12	34	theme	potential	1437:1445	arg1	residues					1479:1486	lamin A residues 622⁻625 and 639⁻645	1471:1506	lamin A residues 622⁻625 and 639⁻645	1471:1506	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	3	35	theme	566	314:316	arg1	residues					318:325	their first 566 residues	302:325	their first 566 residues	302:325	Lamins A and C are identical for their first 566 residues.
29772801	6	36	theme	lamin	651:655	arg1	residues					666:673	residues 385⁻646	666:681	residues 385⁻646	666:681	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	36	theme	lamin	651:655	arg1	tails					659:663	recombinant mature lamin A tails	632:663	recombinant mature lamin A tails (residues 385⁻646)	632:682	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	37	theme	lamin	720:724	arg1	B1					726:727	lamin B1	720:727	lamin B1	720:727	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	14	38	theme	future	1750:1755	arg1	testing					1757:1763	future testing	1750:1763	future testing	1750:1763	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	6	39	theme	recombinant	632:642	arg1	residues					666:673	residues 385⁻646	666:681	residues 385⁻646	666:681	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	39	theme	recombinant	632:642	arg1	tails					659:663	recombinant mature lamin A tails	632:663	recombinant mature lamin A tails (residues 385⁻646)	632:682	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	8	40	theme	Most	897:900	arg1	sites					902:906	Most sites	897:906	Most sites	897:906	Most sites were unpredicted by current algorithms.
29772801	6	41	theme	A	657:657	arg1	residues					666:673	residues 385⁻646	666:681	residues 385⁻646	666:681	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	41	theme	A	657:657	arg1	tails					659:663	recombinant mature lamin A tails	632:663	recombinant mature lamin A tails (residues 385⁻646)	632:682	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	13	42	theme	novel	1609:1613	arg1	pathway					1625:1631	a novel molecular pathway	1607:1631	a novel molecular pathway that may profoundly influence lamin A function	1607:1678	These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function.
29772801	10	43	theme	progeria	1153:1160	arg1	syndrome					1162:1169	Hutchinson⁻Gilford progeria syndrome	1134:1169	Hutchinson⁻Gilford progeria syndrome	1134:1169	By contrast, O-GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson⁻Gilford progeria syndrome, and greatly reduced by deletion Δ35.
29772801	7	44	theme	O-GlcNAc	808:815	arg1	sites					817:821	11 O-GlcNAc sites	805:821	11 O-GlcNAc sites in a 'sweet spot' unique to lamin A	805:857	Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide.
29772801	9	45	from	sites	1037:1041	arg1	O-GlcNAc-modified					1010:1026	O-GlcNAc-modified	1010:1026	O-GlcNAc-modified	1010:1026	Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites.
29772801	6	46	theme	progerin	743:750	arg1	tails					759:763	'progerin' (Δ50) tails	742:763	'progerin' (Δ50) tails	742:763	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	9	47	theme	A	982:982	arg1	tails					984:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites.
29772801	5	48	theme	mouse	522:526	arg1	liver					528:532	mouse liver	522:532	mouse liver	522:532	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	1	49	theme	nuclear	140:146	arg1	structure					148:156	nuclear structure	140:156	nuclear structure	140:156	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	12	50	theme	identified	1398:1407	arg1	sites					1418:1422	identified O-GlcNAc sites	1398:1422	identified O-GlcNAc sites	1398:1422	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	13	51	theme	biochemical	1549:1559	arg1	results					1561:1567	These biochemical results	1543:1567	These biochemical results	1543:1567	These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function.
29772801	5	52	link	β-O-linked	433:442	arg1	O-GlcNAc					465:472	O-GlcNAc	465:472	O-GlcNAc	465:472	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	5	52	link	β-O-linked	433:442	arg1	N-acetylglucosamine-					444:463	β-O-linked N-acetylglucosamine-	433:463	β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver	433:532	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	6	53	theme	tails	659:663	arg1	O-GlcNAcylation					613:627	robust O-GlcNAcylation	606:627	robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646)	606:682	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	12	54	theme	sites	1418:1422	arg1	majority					1386:1393	the majority	1382:1393	the majority of identified O-GlcNAc sites	1382:1422	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	14	55	theme	wildtype	1947:1954	arg1	A					1962:1962	wildtype lamin A	1947:1962	wildtype lamin A	1947:1962	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	2	56	dep	diseases	241:248	arg1	laminopathies					252:264	laminopathies	252:264	'laminopathies'	251:265	Mutations in LMNA cause over 12 diseases ('laminopathies').
29772801	5	57	from	-modified	474:482	arg1	liver					528:532	mouse liver	522:532	mouse liver	522:532	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	5	57	from	-modified	474:482	arg1	cells					509:513	human hepatoma (Huh7) cells	487:513	human hepatoma (Huh7) cells	487:513	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	4	58	theme	separate	347:354	arg1	filaments					356:364	separate filaments	347:364	separate filaments	347:364	However, they form separate filaments in vivo, with apparently distinct roles.
29772801	6	59	dep	In	535:536	arg1	vitro					538:542	vitro	538:542	vitro	538:542	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	60	theme	In	535:536	arg1	assays					544:549	In vitro assays	535:549	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme	535:597	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	0	61	theme	Unique	66:71	arg1	Residues					57:64	Multiple Residues	48:64	Multiple Residues Unique to Lamin A	48:82	OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.
29772801	12	62	theme	homologous	1509:1518	arg1	motifs					1463:1468	potential OGT-association motifs	1437:1468	potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1	1437:1540	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	12	62	theme	homologous	1509:1518	arg1	residues					1479:1486	lamin A residues 622⁻625 and 639⁻645	1471:1506	lamin A residues 622⁻625 and 639⁻645	1471:1506	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	0	63	theme	Lamin	76:80	arg1	A					82:82	Lamin A	76:82	Lamin A	76:82	OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.
29772801	5	64	theme	β-O-linked	433:442	arg1	O-GlcNAc					465:472	O-GlcNAc	465:472	O-GlcNAc	465:472	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	5	64	theme	β-O-linked	433:442	arg1	N-acetylglucosamine-					444:463	β-O-linked N-acetylglucosamine-	433:463	β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver	433:532	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	12	65	theme	A	1477:1477	arg1	motifs					1463:1468	potential OGT-association motifs	1437:1468	potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1	1437:1540	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	12	65	theme	A	1477:1477	arg1	residues					1479:1486	lamin A residues 622⁻625 and 639⁻645	1471:1506	lamin A residues 622⁻625 and 639⁻645	1471:1506	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	5	66	theme	Huh7	503:506	arg1	cells					509:513	human hepatoma (Huh7) cells	487:513	human hepatoma (Huh7) cells	487:513	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	14	67	theme	other	1901:1905	arg1	stresses					1907:1914	nutrient or other stresses	1889:1914	stresses	1907:1914	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	1	68	with	lamins	107:112	arg1	roles					131:135	key roles	127:135	key roles in nuclear structure, signaling, gene regulation, and genome integrity	127:206	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29772801	12	69	theme	OGT-association	1447:1461	arg1	motifs					1463:1468	potential OGT-association motifs	1437:1468	potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1	1437:1540	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	12	69	theme	OGT-association	1447:1461	arg1	residues					1479:1486	lamin A residues 622⁻625 and 639⁻645	1471:1506	lamin A residues 622⁻625 and 639⁻645	1471:1506	Interestingly, deletion Δ35, which does not remove the majority of identified O-GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1.
29772801	14	70	theme	nutrient	1889:1896	arg1	stresses					1907:1914	nutrient or other stresses	1889:1914	stresses	1907:1914	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	13	71	theme	A	1669:1669	arg1	function					1671:1678	lamin A function	1663:1678	lamin A function	1663:1678	These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function.
29772801	7	72	theme	mass	772:775	arg1	spectrometry					777:788	mass spectrometry	772:788	mass spectrometry	772:788	Using mass spectrometry, we identified 11 O-GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide.
29772801	3	73	theme	first	308:312	arg1	residues					318:325	their first 566 residues	302:325	their first 566 residues	302:325	Lamins A and C are identical for their first 566 residues.
29772801	6	74	theme	transferase	574:584	arg1	enzyme					592:597	purified O-GlcNAc transferase (OGT) enzyme	556:597	purified O-GlcNAc transferase (OGT) enzyme	556:597	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	5	75	from	liver	528:532	arg1	-modified					474:482	-modified	474:482	-modified	474:482	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	5	76	theme	hepatoma	493:500	arg1	cells					509:513	human hepatoma (Huh7) cells	487:513	human hepatoma (Huh7) cells	487:513	We report that lamin A is β-O-linked N-acetylglucosamine-(O-GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver.
29772801	14	77	theme	OGT-dependent	1859:1871	arg1	regulation					1873:1882	OGT-dependent regulation	1859:1882	OGT-dependent regulation	1859:1882	The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.
29772801	6	78	theme	purified	556:563	arg1	enzyme					592:597	purified O-GlcNAc transferase (OGT) enzyme	556:597	purified O-GlcNAc transferase (OGT) enzyme	556:597	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	79	theme	lamin	730:734	arg1	C					736:736	lamin C	730:736	lamin C	730:736	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	2	80	from	Mutations	209:217	arg1	LMNA					222:225	LMNA	222:225	LMNA	222:225	Mutations in LMNA cause over 12 diseases ('laminopathies').
29772801	3	81	dep	Lamins	269:274	arg1	Lamins					269:274	Lamins A and C	269:282	Lamins A and C	269:282	Lamins A and C are identical for their first 566 residues.
29772801	3	81	dep	Lamins	269:274	arg1	C					282:282	C	282:282	C	282:282	Lamins A and C are identical for their first 566 residues.
29772801	3	81	dep	Lamins	269:274	arg1	A					276:276	A	276:276	A	276:276	Lamins A and C are identical for their first 566 residues.
29772801	10	82	theme	Hutchinson⁻Gilford	1134:1151	arg1	syndrome					1162:1169	Hutchinson⁻Gilford progeria syndrome	1134:1169	Hutchinson⁻Gilford progeria syndrome	1134:1169	By contrast, O-GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson⁻Gilford progeria syndrome, and greatly reduced by deletion Δ35.
29772801	0	83	theme	Multiple	48:55	arg1	Residues					57:64	Multiple Residues	48:64	Multiple Residues Unique to Lamin A	48:82	OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.
29772801	6	84	theme	B1	726:727	arg1	modification					704:715	no detectable modification	690:715	no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails	690:763	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	85	theme	mature	644:649	arg1	residues					666:673	residues 385⁻646	666:681	residues 385⁻646	666:681	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	85	theme	mature	644:649	arg1	tails					659:663	recombinant mature lamin A tails	632:663	recombinant mature lamin A tails (residues 385⁻646)	632:682	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	86	theme	robust	606:611	arg1	O-GlcNAcylation					613:627	robust O-GlcNAcylation	606:627	robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646)	606:682	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	6	87	theme	detectable	693:702	arg1	modification					704:715	no detectable modification	690:715	no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails	690:763	In vitro assays with purified O-GlcNAc transferase (OGT) enzyme showed robust O-GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails.
29772801	9	88	theme	Double-mutant	948:960	arg1	tails					984:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails	948:988	Double-mutant (S612A/T643A) lamin A tails were still robustly O-GlcNAc-modified at seven sites.
29772801	1	89	theme	genome	191:196	arg1	integrity					198:206	genome integrity	191:206	genome integrity	191:206	The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity.
29460206	0	0	theme	commensal	92:100	arg1	caccae					115:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach.
29460206	4	1	theme	specialised	567:577	arg1	muciniphila					606:616	the specialised mucin-degrader Akkermansia muciniphila	563:616	the specialised mucin-degrader Akkermansia muciniphila	563:616	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	13	2	theme	microbial	1933:1941	arg1	community					1943:1951	the microbial community	1929:1951	the microbial community in the mucosal environment	1929:1978	This could indicate its role as a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars.
29460206	2	3	from	layer	322:326	arg1	flux					279:282	The constant flux	266:282	The constant flux of host-secreted mucin at the mucosal layer	266:326	The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization.
29460206	0	4	theme	gut	88:90	arg1	caccae					115:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach.
29460206	8	5	with	response	1278:1285	arg1	expression					1302:1311	increased expression	1292:1311	increased expression of mucin degradation genes	1292:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	8	6	theme	expression	1161:1170	arg1	DESeq 2					1182:1188	DESeq 2	1182:1188	DESeq 2	1182:1188	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	8	6	theme	expression	1161:1170	arg1	analysis					1172:1179	Differential expression analysis	1148:1179	Differential expression analysis (DESeq 2)	1148:1189	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	6	7	theme	transcription	940:952	arg1	PCR					954:956	quantitative reverse transcription PCR	919:956	quantitative reverse transcription PCR	919:956	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	6	7	theme	transcription	940:952	arg1	composition					906:916	microbial composition	896:916	microbial composition (quantitative reverse transcription PCR)	896:957	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	5	8	dep	A.	671:672	arg1	muciniphila					674:684	muciniphila	674:684	muciniphila	674:684	A. muciniphila monocultures and co-cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown anaerobically in minimal media supplemented with mucin.
29460206	8	9	theme	transcriptional	1262:1276	arg1	response					1278:1285	the A. muciniphila transcriptional response	1243:1285	the A. muciniphila transcriptional response with increased expression of mucin degradation genes	1243:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	4	10	theme	Akkermansia	594:604	arg1	muciniphila					606:616	the specialised mucin-degrader Akkermansia muciniphila	563:616	the specialised mucin-degrader Akkermansia muciniphila	563:616	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	13	11	theme	keystone	1898:1905	arg1	species					1907:1913	a keystone species	1896:1913	a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars	1896:2025	This could indicate its role as a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars.
29460206	6	12	theme	reverse	932:938	arg1	PCR					954:956	quantitative reverse transcription PCR	919:956	quantitative reverse transcription PCR	919:956	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	6	12	theme	reverse	932:938	arg1	composition					906:916	microbial composition	896:916	microbial composition (quantitative reverse transcription PCR)	896:957	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	2	13	theme	mucosal	314:320	arg1	layer					322:326	the mucosal layer	310:326	the mucosal layer	310:326	The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization.
29460206	11	14	theme	microbial	1691:1699	arg1	ecology					1701:1707	the mucin-driven microbial ecology	1674:1707	the mucin-driven microbial ecology using metatranscriptomics	1674:1733	This study provides insight to understand the mucin-driven microbial ecology using metatranscriptomics.
29460206	9	15	theme	efflux	1452:1457	arg1	system					1459:1464	an efflux system	1449:1464	an efflux system	1449:1464	Two putative operons that encode for uncharacterised proteins and an efflux system, and several two-component systems were also differentially regulated.
29460206	0	16	theme	Anaerostipes	102:113	arg1	caccae					115:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach.
29460206	9	17	theme	two-component	1479:1491	arg1	systems					1493:1499	several two-component systems	1471:1499	several two-component systems	1471:1499	Two putative operons that encode for uncharacterised proteins and an efflux system, and several two-component systems were also differentially regulated.
29460206	6	18	theme	quantitative	919:930	arg1	PCR					954:956	quantitative reverse transcription PCR	919:956	quantitative reverse transcription PCR	919:956	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	6	18	theme	quantitative	919:930	arg1	composition					906:916	microbial composition	896:916	microbial composition (quantitative reverse transcription PCR)	896:957	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	13	19	theme	mucosal	1960:1966	arg1	environment					1968:1978	the mucosal environment	1956:1978	the mucosal environment	1956:1978	This could indicate its role as a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars.
29460206	12	20	theme	member	1856:1861	arg1	presence					1832:1839	the presence	1828:1839	the presence of a community member	1828:1861	Our findings show that the expression of mucolytic enzymes by A. muciniphila increases upon the presence of a community member.
29460206	8	21	from	changes	1232:1238	arg1	response					1278:1285	the A. muciniphila transcriptional response	1243:1285	the A. muciniphila transcriptional response with increased expression of mucin degradation genes	1243:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	8	22	theme	mucin	1316:1320	arg1	genes					1334:1338	mucin degradation genes	1316:1338	mucin degradation genes	1316:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	4	23	theme	trophic	535:541	arg1	interaction					543:553	mucin-driven trophic interaction	522:553	mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal	522:648	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	10	24	dep	indicated	1542:1550	arg1	changed					1567:1573	changed	1567:1573	indicated A. muciniphila changed its transcriptional regulation in response to A. caccae	1542:1629	This indicated A. muciniphila changed its transcriptional regulation in response to A. caccae.
29460206	12	25	theme	community	1846:1854	arg1	member					1856:1861	a community member	1844:1861	a community member	1844:1861	Our findings show that the expression of mucolytic enzymes by A. muciniphila increases upon the presence of a community member.
29460206	3	26	theme	Mucin	379:383	arg1	degradation					385:395	Mucin degradation	379:395	Mucin degradation by keystone species	379:415	Mucin degradation by keystone species subsequently shapes the microbial community.
29460206	13	27	from	community	1943:1951	arg1	environment					1968:1978	the mucosal environment	1956:1978	the mucosal environment	1956:1978	This could indicate its role as a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars.
29460206	5	28	theme	A.	671:672	arg1	monocultures					686:697	A. muciniphila monocultures	671:697	A. muciniphila monocultures	671:697	A. muciniphila monocultures and co-cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown anaerobically in minimal media supplemented with mucin.
29460206	2	29	theme	mucin	301:305	arg1	flux					279:282	The constant flux	266:282	The constant flux of host-secreted mucin at the mucosal layer	266:326	The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization.
29460206	9	30	theme	putative	1387:1394	arg1	operons					1396:1402	Two putative operons	1383:1402	Two putative operons that encode for uncharacterised proteins and an efflux system	1383:1464	Two putative operons that encode for uncharacterised proteins and an efflux system, and several two-component systems were also differentially regulated.
29460206	5	31	with	co-cultures	703:713	arg1	caccae					737:742	non-mucolytic A. caccae	720:742	non-mucolytic A. caccae from the Lachnospiraceae family	720:774	A. muciniphila monocultures and co-cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown anaerobically in minimal media supplemented with mucin.
29460206	7	32	theme	caccae	1063:1068	arg1	growth					1050:1055	the growth	1046:1055	the growth of A. caccae and concomitant butyrate production	1046:1104	Mucin degradation by A. muciniphila supported the growth of A. caccae and concomitant butyrate production predominantly via the acetyl-CoA pathway.
29460206	9	33	theme	several	1471:1477	arg1	systems					1493:1499	several two-component systems	1471:1499	several two-component systems	1471:1499	Two putative operons that encode for uncharacterised proteins and an efflux system, and several two-component systems were also differentially regulated.
29460206	6	34	theme	microbial	896:904	arg1	PCR					954:956	quantitative reverse transcription PCR	919:956	quantitative reverse transcription PCR	919:956	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	6	34	theme	microbial	896:904	arg1	composition					906:916	microbial composition	896:916	microbial composition (quantitative reverse transcription PCR)	896:957	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	2	35	theme	steady	338:343	arg1	niche					345:349	a steady niche	336:349	a steady niche for bacterial colonization	336:376	The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization.
29460206	1	36	theme	symbiotic	204:212	arg1	relationship					214:225	the symbiotic relationship	200:225	the symbiotic relationship between humans and their gut bacteria	200:263	Host glycans are paramount in regulating the symbiotic relationship between humans and their gut bacteria.
29460206	8	37	theme	degradation	1322:1332	arg1	genes					1334:1338	mucin degradation genes	1316:1338	mucin degradation genes	1316:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	5	38	with	monocultures	686:697	arg1	caccae					737:742	non-mucolytic A. caccae	720:742	non-mucolytic A. caccae from the Lachnospiraceae family	720:774	A. muciniphila monocultures and co-cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown anaerobically in minimal media supplemented with mucin.
29460206	5	39	theme	Lachnospiraceae	753:767	arg1	family					769:774	the Lachnospiraceae family	749:774	the Lachnospiraceae family	749:774	A. muciniphila monocultures and co-cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown anaerobically in minimal media supplemented with mucin.
29460206	8	40	theme	Differential	1148:1159	arg1	DESeq 2					1182:1188	DESeq 2	1182:1188	DESeq 2	1182:1188	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	8	40	theme	Differential	1148:1159	arg1	analysis					1172:1179	Differential expression analysis	1148:1179	Differential expression analysis (DESeq 2)	1148:1189	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	3	41	theme	keystone	400:407	arg1	species					409:415	keystone species	400:415	keystone species	400:415	Mucin degradation by keystone species subsequently shapes the microbial community.
29460206	10	42	theme	transcriptional	1579:1593	arg1	regulation					1595:1604	its transcriptional regulation	1575:1604	its transcriptional regulation	1575:1604	This indicated A. muciniphila changed its transcriptional regulation in response to A. caccae.
29460206	7	43	theme	concomitant	1074:1084	arg1	production					1095:1104	concomitant butyrate production	1074:1104	concomitant butyrate production	1074:1104	Mucin degradation by A. muciniphila supported the growth of A. caccae and concomitant butyrate production predominantly via the acetyl-CoA pathway.
29460206	0	44	theme	trophic	16:22	arg1	interaction					24:34	the trophic interaction	12:34	the trophic interaction between Akkermansia muciniphila	12:66	Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach.
29460206	0	45	theme	metatranscriptomic	130:147	arg1	approach					149:156	a metatranscriptomic approach	128:156	a metatranscriptomic approach	128:156	Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach.
29460206	13	46	theme	sugars	2020:2025	arg1	availability					1998:2009	the availability	1994:2009	the availability of mucin sugars	1994:2025	This could indicate its role as a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars.
29460206	4	47	theme	transcriptional	490:504	arg1	response					506:513	the transcriptional response	486:513	the transcriptional response	486:513	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	8	48	dep	showed	1191:1196	arg1	reduced					1344:1350	reduced	1344:1350	reduced expression of ribosomal genes	1344:1380	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	8	48	dep	showed	1191:1196	arg1	induced					1224:1230	induced	1224:1230	induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes	1224:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	8	49	theme	caccae	1217:1222	arg1	presence					1202:1209	the presence	1198:1209	the presence of A. caccae	1198:1222	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	4	50	theme	mucin-driven	522:533	arg1	interaction					543:553	mucin-driven trophic interaction	522:553	mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal	522:648	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	12	51	theme	enzymes	1787:1793	arg1	expression					1763:1772	the expression	1759:1772	the expression of mucolytic enzymes by A. muciniphila	1759:1811	Our findings show that the expression of mucolytic enzymes by A. muciniphila increases upon the presence of a community member.
29460206	8	52	theme	genes	1376:1380	arg1	expression					1352:1361	expression	1352:1361	expression of ribosomal genes	1352:1380	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	12	53	theme	mucolytic	1777:1785	arg1	enzymes					1787:1793	mucolytic enzymes	1777:1793	mucolytic enzymes	1777:1793	Our findings show that the expression of mucolytic enzymes by A. muciniphila increases upon the presence of a community member.
29460206	6	54	theme	transcriptional	964:978	arg1	response					980:987	transcriptional response	964:987	transcriptional response (RNA-seq)	964:997	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	6	54	theme	transcriptional	964:978	arg1	RNA-seq					990:996	RNA-seq	990:996	RNA-seq	990:996	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	13	55	theme	mucin	2014:2018	arg1	sugars					2020:2025	mucin sugars	2014:2025	mucin sugars	2014:2025	This could indicate its role as a keystone species that supports the microbial community in the mucosal environment by increasing the availability of mucin sugars.
29460206	6	56	theme	HPLC	880:883	arg1	metabolites					867:877	metabolites	867:877	metabolites (HPLC analysis)	867:893	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	6	56	theme	HPLC	880:883	arg1	analysis					885:892	HPLC analysis	880:892	HPLC analysis	880:892	We analysed for growth, metabolites (HPLC analysis), microbial composition (quantitative reverse transcription PCR), and transcriptional response (RNA-seq).
29460206	11	57	theme	mucin-driven	1678:1689	arg1	ecology					1701:1707	the mucin-driven microbial ecology	1674:1707	the mucin-driven microbial ecology using metatranscriptomics	1674:1733	This study provides insight to understand the mucin-driven microbial ecology using metatranscriptomics.
29460206	3	58	theme	microbial	441:449	arg1	community					451:459	the microbial community	437:459	the microbial community	437:459	Mucin degradation by keystone species subsequently shapes the microbial community.
29460206	4	59	theme	gut	636:638	arg1	commensal					640:648	a butyrogenic gut commensal	622:648	a butyrogenic gut commensal	622:648	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	5	60	theme	minimal	804:810	arg1	media					812:816	minimal media	804:816	minimal media supplemented with mucin	804:840	A. muciniphila monocultures and co-cultures with non-mucolytic A. caccae from the Lachnospiraceae family were grown anaerobically in minimal media supplemented with mucin.
29460206	7	61	theme	acetyl-CoA	1128:1137	arg1	pathway					1139:1145	the acetyl-CoA pathway	1124:1145	the acetyl-CoA pathway	1124:1145	Mucin degradation by A. muciniphila supported the growth of A. caccae and concomitant butyrate production predominantly via the acetyl-CoA pathway.
29460206	2	62	theme	bacterial	355:363	arg1	colonization					365:376	bacterial colonization	355:376	bacterial colonization	355:376	The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization.
29460206	4	63	theme	butyrogenic	624:634	arg1	commensal					640:648	a butyrogenic gut commensal	622:648	a butyrogenic gut commensal	622:648	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	8	64	theme	A.	1247:1248	arg1	response					1278:1285	the A. muciniphila transcriptional response	1243:1285	the A. muciniphila transcriptional response with increased expression of mucin degradation genes	1243:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	2	65	theme	host-secreted	287:299	arg1	mucin					301:305	host-secreted mucin	287:305	host-secreted mucin	287:305	The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization.
29460206	7	66	theme	butyrate	1086:1093	arg1	production					1095:1104	concomitant butyrate production	1074:1104	concomitant butyrate production	1074:1104	Mucin degradation by A. muciniphila supported the growth of A. caccae and concomitant butyrate production predominantly via the acetyl-CoA pathway.
29460206	1	67	theme	gut	252:254	arg1	bacteria					256:263	their gut bacteria	246:263	their gut bacteria	246:263	Host glycans are paramount in regulating the symbiotic relationship between humans and their gut bacteria.
29460206	8	68	dep	A.	1247:1248	arg1	muciniphila					1250:1260	muciniphila	1250:1260	muciniphila	1250:1260	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	8	69	theme	ribosomal	1366:1374	arg1	genes					1376:1380	ribosomal genes	1366:1380	ribosomal genes	1366:1380	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	1	70	theme	Host	159:162	arg1	glycans					164:170	Host glycans	159:170	Host glycans	159:170	Host glycans are paramount in regulating the symbiotic relationship between humans and their gut bacteria.
29460206	0	71	theme	butyrogenic	76:86	arg1	caccae					115:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	the butyrogenic gut commensal Anaerostipes caccae	72:120	Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach.
29460206	9	72	theme	uncharacterised	1420:1434	arg1	proteins					1436:1443	uncharacterised proteins	1420:1443	uncharacterised proteins	1420:1443	Two putative operons that encode for uncharacterised proteins and an efflux system, and several two-component systems were also differentially regulated.
29460206	10	73	dep	caccae	1624:1629	arg1	response					1609:1616	response	1609:1616	response	1609:1616	This indicated A. muciniphila changed its transcriptional regulation in response to A. caccae.
29460206	4	74	theme	mucin-degrader	579:592	arg1	muciniphila					606:616	the specialised mucin-degrader Akkermansia muciniphila	563:616	the specialised mucin-degrader Akkermansia muciniphila	563:616	This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae.
29460206	2	75	theme	constant	270:277	arg1	flux					279:282	The constant flux	266:282	The constant flux of host-secreted mucin at the mucosal layer	266:326	The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization.
29460206	7	76	theme	production	1095:1104	arg1	growth					1050:1055	the growth	1046:1055	the growth of A. caccae and concomitant butyrate production	1046:1104	Mucin degradation by A. muciniphila supported the growth of A. caccae and concomitant butyrate production predominantly via the acetyl-CoA pathway.
29460206	8	77	theme	genes	1334:1338	arg1	expression					1302:1311	increased expression	1292:1311	increased expression of mucin degradation genes	1292:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29460206	7	78	theme	Mucin	1000:1004	arg1	degradation					1006:1016	Mucin degradation	1000:1016	Mucin degradation by A. muciniphila	1000:1034	Mucin degradation by A. muciniphila supported the growth of A. caccae and concomitant butyrate production predominantly via the acetyl-CoA pathway.
29460206	8	79	theme	increased	1292:1300	arg1	expression					1302:1311	increased expression	1292:1311	increased expression of mucin degradation genes	1292:1338	Differential expression analysis (DESeq 2) showed the presence of A. caccae induced changes in the A. muciniphila transcriptional response with increased expression of mucin degradation genes and reduced expression of ribosomal genes.
29459785	6	0	theme	Structural	977:986	arg1	analyses					1003:1010	Structural and functional analyses	977:1010	Structural and functional analyses	977:1010	Structural and functional analyses reveal the difference between GPT and MraY in their mechanisms of inhibition by tunicamycin.
29459785	6	1	from	difference	1023:1032	arg1	mechanisms					1064:1073	their mechanisms	1058:1073	their mechanisms of inhibition by tunicamycin	1058:1102	Structural and functional analyses reveal the difference between GPT and MraY in their mechanisms of inhibition by tunicamycin.
29459785	2	2	link	N-linked	432:439	arg1	glycosylation					441:453	N-linked glycosylation	432:453	N-linked glycosylation	432:453	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	3	from	step	424:427	arg1	membrane					484:491	the endoplasmic reticulum membrane	458:491	the endoplasmic reticulum membrane	458:491	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	4	theme	glycosylation	441:453	arg1	step					424:427	the first and committed step	400:427	the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane	400:491	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	1	5	link	N-linked	102:109	arg1	modification					161:172	a predominant post-translational modification	128:172	a predominant post-translational modification of protein in eukaryotes	128:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	5	link	N-linked	102:109	arg1	glycosylation					111:123	N-linked glycosylation	102:123	N-linked glycosylation	102:123	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	3	6	theme	bacterial	613:621	arg1	MraY					650:653	the bacterial cell wall synthesis enzyme MraY	609:653	the bacterial cell wall synthesis enzyme MraY	609:653	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	3	7	theme	enzyme	643:648	arg1	MraY					650:653	the bacterial cell wall synthesis enzyme MraY	609:653	the bacterial cell wall synthesis enzyme MraY	609:653	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	3	8	theme	antibacterial	574:586	arg1	activity					588:595	potent antibacterial activity	567:595	potent antibacterial activity	567:595	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	4	9	theme	N-linked	788:795	arg1	glycosylation					797:809	N-linked glycosylation	788:809	N-linked glycosylation	788:809	Our understanding of how tunicamycin inhibits N-linked glycosylation and efforts to selectively target MraY are hampered by a lack of structural information.
29459785	5	10	from	structures	924:933	arg1	complex					951:957	complex	951:957	complex with tunicamycin	951:974	Here we present crystal structures of human GPT in complex with tunicamycin.
29459785	5	11	theme	human	938:942	arg1	GPT					944:946	human GPT	938:946	human GPT in complex with tunicamycin	938:974	Here we present crystal structures of human GPT in complex with tunicamycin.
29459785	1	12	theme	N-linked	102:109	arg1	modification					161:172	a predominant post-translational modification	128:172	a predominant post-translational modification of protein in eukaryotes	128:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	12	theme	N-linked	102:109	arg1	glycosylation					111:123	N-linked glycosylation	102:123	N-linked glycosylation	102:123	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	0	13	theme	GlcNAc-1-P-transferase-tunicamycin	0:33	arg1	structure					43:51	GlcNAc-1-P-transferase-tunicamycin complex structure	0:51	GlcNAc-1-P-transferase-tunicamycin complex structure	0:51	GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition of N-glycosylation.
29459785	0	14	theme	complex	35:41	arg1	structure					43:51	GlcNAc-1-P-transferase-tunicamycin complex structure	0:51	GlcNAc-1-P-transferase-tunicamycin complex structure	0:51	GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition of N-glycosylation.
29459785	3	15	theme	cell	623:626	arg1	MraY					650:653	the bacterial cell wall synthesis enzyme MraY	609:653	the bacterial cell wall synthesis enzyme MraY	609:653	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	7	16	theme	potential	1198:1206	arg1	antibiotics					1208:1218	potential antibiotics	1198:1218	potential antibiotics	1198:1218	We demonstrate that this difference could be exploited to design MraY-specific inhibitors as potential antibiotics.
29459785	6	17	theme	functional	992:1001	arg1	analyses					1003:1010	Structural and functional analyses	977:1010	Structural and functional analyses	977:1010	Structural and functional analyses reveal the difference between GPT and MraY in their mechanisms of inhibition by tunicamycin.
29459785	2	18	theme	natural	522:528	arg1	tunicamycin					538:548	the natural product tunicamycin	518:548	the natural product tunicamycin	518:548	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	6	19	theme	inhibition	1078:1087	arg1	mechanisms					1064:1073	their mechanisms	1058:1073	their mechanisms of inhibition by tunicamycin	1058:1102	Structural and functional analyses reveal the difference between GPT and MraY in their mechanisms of inhibition by tunicamycin.
29459785	1	20	from	modification	161:172	arg1	eukaryotes					188:197	eukaryotes	188:197	eukaryotes	188:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	2	21	theme	first	404:408	arg1	step					424:427	the first and committed step	400:427	the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane	400:491	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	22	theme	reticulum	474:482	arg1	membrane					484:491	the endoplasmic reticulum membrane	458:491	the endoplasmic reticulum membrane	458:491	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	5	23	theme	GPT	944:946	arg1	structures					924:933	crystal structures	916:933	crystal structures of human GPT in complex with tunicamycin	916:974	Here we present crystal structures of human GPT in complex with tunicamycin.
29459785	1	24	theme	predominant	130:140	arg1	modification					161:172	a predominant post-translational modification	128:172	a predominant post-translational modification of protein in eukaryotes	128:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	24	theme	predominant	130:140	arg1	glycosylation					111:123	N-linked glycosylation	102:123	N-linked glycosylation	102:123	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	4	25	link	N-linked	788:795	arg1	glycosylation					797:809	N-linked glycosylation	788:809	N-linked glycosylation	788:809	Our understanding of how tunicamycin inhibits N-linked glycosylation and efforts to selectively target MraY are hampered by a lack of structural information.
29459785	3	26	theme	wall	628:631	arg1	MraY					650:653	the bacterial cell wall synthesis enzyme MraY	609:653	the bacterial cell wall synthesis enzyme MraY	609:653	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	3	27	theme	GPT	737:739	arg1	inhibition					717:726	off-target inhibition	706:726	off-target inhibition of human GPT	706:739	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	1	28	theme	post-translational	142:159	arg1	modification					161:172	a predominant post-translational modification	128:172	a predominant post-translational modification of protein in eukaryotes	128:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	28	theme	post-translational	142:159	arg1	glycosylation					111:123	N-linked glycosylation	102:123	N-linked glycosylation	102:123	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	29	theme	several	241:247	arg1	disorders					255:263	several human disorders	241:263	several human disorders	241:263	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	2	30	dep	UDP-N-acetylglucosamine	277:299	arg1	it					498:499	it	498:499	it	498:499	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	30	dep	UDP-N-acetylglucosamine	277:299	arg1	catalyzes					390:398	catalyzes	390:398	catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane	390:491	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	30	dep	UDP-N-acetylglucosamine	277:299	arg1	target					508:513	the target	504:513	the target of the natural product tunicamycin	504:548	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	31	dep	N-acetylglucosaminephosphotransferase	320:356	arg1	GPT					385:387	GPT	385:387	GPT	385:387	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	31	dep	N-acetylglucosaminephosphotransferase	320:356	arg1	GlcNAc-1-P-transferase					359:380	GlcNAc-1-P-transferase	359:380	GlcNAc-1-P-transferase	359:380	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	1	32	theme	human	249:253	arg1	disorders					255:263	several human disorders	241:263	several human disorders	241:263	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	7	33	theme	MraY-specific	1170:1182	arg1	inhibitors					1184:1193	MraY-specific inhibitors	1170:1193	MraY-specific inhibitors as potential antibiotics	1170:1218	We demonstrate that this difference could be exploited to design MraY-specific inhibitors as potential antibiotics.
29459785	3	34	contain	has	563:565	arg1	Tunicamycin					551:561	Tunicamycin	551:561	Tunicamycin	551:561	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	3	34	contain	has	563:565	arg2	activity					588:595	potent antibacterial activity	567:595	potent antibacterial activity	567:595	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	2	35	theme	enzyme	270:275	arg1	UDP-N-acetylglucosamine					277:299	The enzyme UDP-N-acetylglucosamine	266:299	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.	266:549	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	5	36	from	GPT	944:946	arg1	complex					951:957	complex	951:957	complex with tunicamycin	951:974	Here we present crystal structures of human GPT in complex with tunicamycin.
29459785	1	37	theme	disorders	255:263	arg1	modification					161:172	a predominant post-translational modification	128:172	a predominant post-translational modification of protein in eukaryotes	128:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	37	theme	disorders	255:263	arg1	etiology					229:236	the etiology	225:236	the etiology of several human disorders	225:263	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	37	theme	disorders	255:263	arg1	dysregulation					208:220	its dysregulation	204:220	its dysregulation	204:220	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	37	theme	disorders	255:263	arg1	glycosylation					111:123	N-linked glycosylation	102:123	N-linked glycosylation	102:123	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	3	38	theme	human	731:735	arg1	GPT					737:739	human GPT	731:739	human GPT	731:739	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	2	39	theme	N-linked	432:439	arg1	glycosylation					441:453	N-linked glycosylation	432:453	N-linked glycosylation	432:453	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	40	theme	tunicamycin	538:548	arg1	it					498:499	it	498:499	it	498:499	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	2	40	theme	tunicamycin	538:548	arg1	target					508:513	the target	504:513	the target of the natural product tunicamycin	504:548	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	5	41	theme	crystal	916:922	arg1	structures					924:933	crystal structures	916:933	crystal structures of human GPT in complex with tunicamycin	916:974	Here we present crystal structures of human GPT in complex with tunicamycin.
29459785	5	42	with	complex	951:957	arg1	tunicamycin					964:974	tunicamycin	964:974	tunicamycin	964:974	Here we present crystal structures of human GPT in complex with tunicamycin.
29459785	4	43	theme	information	887:897	arg1	lack					868:871	a lack	866:871	a lack of structural information	866:897	Our understanding of how tunicamycin inhibits N-linked glycosylation and efforts to selectively target MraY are hampered by a lack of structural information.
29459785	3	44	theme	off-target	706:715	arg1	inhibition					717:726	off-target inhibition	706:726	off-target inhibition of human GPT	706:739	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	1	45	theme	protein	177:183	arg1	modification					161:172	a predominant post-translational modification	128:172	a predominant post-translational modification of protein in eukaryotes	128:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	45	theme	protein	177:183	arg1	etiology					229:236	the etiology	225:236	the etiology of several human disorders	225:263	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	45	theme	protein	177:183	arg1	dysregulation					208:220	its dysregulation	204:220	its dysregulation	204:220	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	1	45	theme	protein	177:183	arg1	glycosylation					111:123	N-linked glycosylation	102:123	N-linked glycosylation	102:123	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	3	46	theme	synthesis	633:641	arg1	MraY					650:653	the bacterial cell wall synthesis enzyme MraY	609:653	the bacterial cell wall synthesis enzyme MraY	609:653	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	4	47	theme	structural	876:885	arg1	information					887:897	structural information	876:897	structural information	876:897	Our understanding of how tunicamycin inhibits N-linked glycosylation and efforts to selectively target MraY are hampered by a lack of structural information.
29459785	2	48	theme	committed	414:422	arg1	step					424:427	the first and committed step	400:427	the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane	400:491	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	3	49	theme	potent	567:572	arg1	activity					588:595	potent antibacterial activity	567:595	potent antibacterial activity	567:595	Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT.
29459785	2	50	theme	dolichyl-phosphate	301:318	arg1	N-acetylglucosaminephosphotransferase					320:356	dolichyl-phosphate N-acetylglucosaminephosphotransferase	301:356	dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT)	301:388	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	1	51	from	etiology	229:236	arg1	eukaryotes					188:197	eukaryotes	188:197	eukaryotes	188:197	N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders.
29459785	2	52	theme	endoplasmic	462:472	arg1	reticulum					474:482	the endoplasmic reticulum	458:482	the endoplasmic reticulum membrane	458:491	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
29459785	0	53	theme	N-glycosylation	85:99	arg1	inhibition					71:80	inhibition	71:80	inhibition of N-glycosylation	71:99	GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition of N-glycosylation.
29459785	5	54	from	complex	951:957	arg1	structures					924:933	crystal structures	916:933	crystal structures of human GPT in complex with tunicamycin	916:974	Here we present crystal structures of human GPT in complex with tunicamycin.
29459785	2	55	theme	product	530:536	arg1	tunicamycin					538:548	the natural product tunicamycin	518:548	the natural product tunicamycin	518:548	The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin.
30455672	2	0	from	colon	538:542	arg1	degradation					492:502	the degradation	488:502	the degradation of resistant starch (RS) in human colon	488:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	3	1	theme	sole	643:646	arg1	source					655:660	sole carbon source	643:660	sole carbon source	643:660	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	8	2	theme	mucus	2135:2139	arg1	niche					2141:2145	the mucus niche	2131:2145	the mucus niche	2131:2145	Together this study showed a direct competition between R. bromii and R. gnavus on RS, suggesting that in vivo, the R. gnavus population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
30455672	6	3	theme	R.	1401:1402	arg1	bromii					1404:1409	R. bromii	1401:1409	R. bromii	1401:1409	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	5	4	theme	1H	1089:1090	arg1	analysis					1096:1103	1H NMR analysis	1089:1103	1H NMR analysis	1089:1103	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	7	5	theme	methionine	1837:1846	arg1	biosynthesis					1848:1859	vitamin B12 (VitB12)-dependent methionine biosynthesis	1806:1859	vitamin B12 (VitB12)-dependent methionine biosynthesis	1806:1859	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	5	6	from	fermentations	1064:1076	arg1	starch					1081:1086	starch	1081:1086	starch	1081:1086	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	5	7	theme	main	1276:1279	arg1	end-products					1294:1305	main fermentation end-products	1276:1305	main fermentation end-products	1276:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	7	8	theme	R.	1972:1973	arg1	gnavus					1975:1980	R. gnavus	1972:1980	R. gnavus	1972:1980	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	3	9	theme	R.	700:701	arg1	bromii					703:708	R. bromii	700:708	R. bromii	700:708	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	1	10	theme	gut	186:188	arg1	microbiota					190:199	the human gut microbiota	176:199	the human gut microbiota	176:199	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	4	11	theme	quantitative	847:858	arg1	growth					839:844	the growth	835:844	the growth (quantitative PCR)	835:863	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	11	theme	quantitative	847:858	arg1	PCR					860:862	quantitative PCR	847:862	quantitative PCR	847:862	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	3	12	dep	R.	734:735	arg1	gnavus					737:742	R. gnavus	734:742	R. gnavus	734:742	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	3	13	dep	R.	591:592	arg1	bromii					594:599	R. bromii	591:599	R. bromii	591:599	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	7	14	theme	vitamin	1806:1812	arg1	B12					1814:1816	vitamin B12	1806:1816	vitamin B12	1806:1816	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	6	15	theme	maltose	1559:1565	arg1	phosphorylase					1567:1579	maltose phosphorylase	1559:1579	maltose phosphorylase	1559:1579	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	1	16	theme	carbohydrate-degrading	215:236	arg1	species					238:244	keystone carbohydrate-degrading species	206:244	keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities	206:339	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	8	17	theme	carbohydrates	2196:2208	arg1	supply					2171:2176	the supply	2167:2176	the supply of non-digestible carbohydrates reaching the colon such as RS	2167:2238	Together this study showed a direct competition between R. bromii and R. gnavus on RS, suggesting that in vivo, the R. gnavus population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
30455672	6	18	theme	gnavus	1433:1438	arg1	response					1456:1463	R. gnavus transcriptional response	1430:1463	R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase	1430:1579	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	1	19	theme	Dietary	126:132	arg1	glycans					143:149	Dietary and host glycans	126:149	Dietary and host glycans	126:149	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	2	20	from	degradation	492:502	arg1	colon					538:542	human colon	532:542	human colon	532:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	7	21	theme	VitB12	1918:1923	arg1	availability					1925:1936	VitB12 availability	1918:1936	VitB12 availability	1918:1936	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	1	22	theme	host	138:141	arg1	glycans					143:149	Dietary and host glycans	126:149	Dietary and host glycans	126:149	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	4	23	theme	NMR	892:894	arg1	production					877:886	metabolite production	866:886	metabolite production (1H NMR analysis)	866:904	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	23	theme	NMR	892:894	arg1	analysis					896:903	1H NMR analysis	889:903	1H NMR analysis	889:903	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	3	24	theme	R.	734:735	arg1	growth					724:729	the growth	720:729	the growth of R. gnavus	720:742	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	3	25	theme	R.	591:592	arg1	individual					561:570	individual	561:570	individual	561:570	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	7	26	from	increase	1723:1730	arg1	induction					1739:1747	the induction	1735:1747	the induction of tryptophan (Trp) biosynthesis genes	1735:1786	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	4	27	theme	R.	1039:1040	arg1	absence					1028:1034	absence	1028:1034	absence	1028:1034	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	27	theme	R.	1039:1040	arg1	presence					1016:1023	the presence	1012:1023	the presence	1012:1023	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	5	28	theme	gnavus	1120:1125	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	0	29	theme	bromii	84:89	arg1	Cross-Feeding					30:42	the Cross-Feeding	26:42	the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates	26:123	Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates.
30455672	6	30	from	changes	1419:1425	arg1	response					1456:1463	R. gnavus transcriptional response	1430:1463	R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase	1430:1579	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	3	31	theme	R.	804:805	arg1	gnavus					807:812	R. gnavus	804:812	R. gnavus	804:812	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	2	32	theme	starch	517:522	arg1	degradation					492:502	the degradation	488:502	the degradation of resistant starch (RS) in human colon	488:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	7	33	theme	genes	1782:1786	arg1	induction					1739:1747	the induction	1735:1747	the induction of tryptophan (Trp) biosynthesis genes	1735:1786	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	5	34	theme	starch	1213:1218	arg1	degradation					1220:1230	starch degradation	1213:1230	starch degradation	1213:1230	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	0	35	theme	Dietary	103:109	arg1	Carbohydrates					111:123	Dietary Carbohydrates	103:123	Dietary Carbohydrates	103:123	Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates.
30455672	6	36	theme	several	1483:1489	arg1	transporters					1499:1510	several maltose transporters	1483:1510	several maltose transporters	1483:1510	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	5	37	from	formate	1252:1258	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	2	38	theme	R.	448:449	arg1	L2-63					458:462	R. bromii L2-63	448:462	R. bromii L2-63	448:462	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	2	38	theme	R.	448:449	arg1	species					476:482	a keystone species	465:482	a keystone species for the degradation of resistant starch (RS) in human colon	465:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	0	39	from	Cross-Feeding	30:42	arg1	Host					94:97	Host	94:97	Host	94:97	Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates.
30455672	0	39	from	Cross-Feeding	30:42	arg1	Carbohydrates					111:123	Dietary Carbohydrates	103:123	Dietary Carbohydrates	103:123	Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates.
30455672	0	40	theme	Mechanistic	0:10	arg1	Insights					12:19	Mechanistic Insights	0:19	Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates.	0:124	Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates.
30455672	6	41	theme	genes	1468:1472	arg1	response					1456:1463	R. gnavus transcriptional response	1430:1463	R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase	1430:1579	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	5	42	from	acetate	1243:1249	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	6	43	theme	degradation	1648:1658	arg1	products					1660:1667	R. bromii starch degradation products	1631:1667	R. bromii starch degradation products	1631:1667	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	2	44	theme	ATCC	432:435	arg1	29149					437:441	the mucin-degrader Ruminococcus gnavus ATCC 29149	393:441	the mucin-degrader Ruminococcus gnavus ATCC 29149	393:441	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	6	45	theme	Differential	1308:1319	arg1	DESeq					1342:1346	DESeq 2	1342:1348	DESeq 2	1342:1348	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	6	45	theme	Differential	1308:1319	arg1	analysis					1332:1339	Differential expression analysis	1308:1339	Differential expression analysis (DESeq 2) on starch (SS and RS)	1308:1371	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	5	46	theme	co-culture	1053:1062	arg1	fermentations					1064:1076	co-culture fermentations	1053:1076	co-culture fermentations on starch	1053:1086	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	6	47	theme	bromii	1634:1639	arg1	products					1660:1667	R. bromii starch degradation products	1631:1667	R. bromii starch degradation products	1631:1667	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	2	48	dep	Ruminococcus	412:423	arg1	gnavus					425:430	gnavus	425:430	gnavus	425:430	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	2	49	theme	Ruminococcus	412:423	arg1	29149					437:441	the mucin-degrader Ruminococcus gnavus ATCC 29149	393:441	the mucin-degrader Ruminococcus gnavus ATCC 29149	393:441	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	1	50	theme	gut	315:317	arg1	communities					329:339	gut microbial communities	315:339	gut microbial communities	315:339	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	7	51	theme	R.	1692:1693	arg1	bromii					1695:1700	R. bromii	1692:1700	R. bromii	1692:1700	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	7	52	theme	biosynthesis	1848:1859	arg1	decrease					1794:1801	a decrease	1792:1801	a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis	1792:1859	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	7	52	theme	biosynthesis	1848:1859	arg1	increase					1723:1730	a significant increase	1709:1730	a significant increase in the induction of tryptophan (Trp) biosynthesis genes	1709:1786	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	4	53	theme	transcriptional	921:935	arg1	RNA-Seq					947:953	RNA-Seq	947:953	RNA-Seq	947:953	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	53	theme	transcriptional	921:935	arg1	response					937:944	bacterial transcriptional response	911:944	bacterial transcriptional response (RNA-Seq)	911:954	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	1	54	theme	communities	329:339	arg1	function					303:310	function	303:310	function	303:310	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	1	54	theme	communities	329:339	arg1	structure					289:297	structure	289:297	structure	289:297	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	8	55	theme	R.	2099:2100	arg1	population					2109:2118	the R. gnavus population	2095:2118	the R. gnavus population inhabiting the mucus niche	2095:2145	Together this study showed a direct competition between R. bromii and R. gnavus on RS, suggesting that in vivo, the R. gnavus population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
30455672	5	56	theme	NMR	1092:1094	arg1	analysis					1096:1103	1H NMR analysis	1089:1103	1H NMR analysis	1089:1103	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	4	57	theme	soluble	989:995	arg1	SS					1005:1006	SS	1005:1006	SS	1005:1006	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	57	theme	soluble	989:995	arg1	starch					997:1002	soluble starch	989:1002	soluble starch (SS)	989:1007	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	2	58	theme	human	372:376	arg1	symbionts					382:390	two major human gut symbionts	362:390	two major human gut symbionts	362:390	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	7	59	from	decrease	1794:1801	arg1	induction					1739:1747	the induction	1735:1747	the induction of tryptophan (Trp) biosynthesis genes	1735:1786	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	4	60	theme	R.	959:960	arg1	PCR					860:862	quantitative PCR	847:862	quantitative PCR	847:862	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	60	theme	R.	959:960	arg1	analysis					896:903	1H NMR analysis	889:903	1H NMR analysis	889:903	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	60	theme	R.	959:960	arg1	response					937:944	bacterial transcriptional response	911:944	bacterial transcriptional response (RNA-Seq)	911:954	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	60	theme	R.	959:960	arg1	growth					839:844	the growth	835:844	the growth (quantitative PCR)	835:863	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	60	theme	R.	959:960	arg1	RNA-Seq					947:953	RNA-Seq	947:953	RNA-Seq	947:953	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	60	theme	R.	959:960	arg1	production					877:886	metabolite production	866:886	metabolite production (1H NMR analysis)	866:904	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	3	61	theme	carbon	648:653	arg1	source					655:660	sole carbon source	643:660	sole carbon source	643:660	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	7	62	dep	-dependent	1826:1835	arg1	B12					1814:1816	vitamin B12	1806:1816	vitamin B12	1806:1816	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	3	63	theme	starch	678:683	arg1	degradation					685:695	starch degradation	678:695	starch degradation by R. bromii	678:708	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	4	64	dep	R.	1039:1040	arg1	gnavus					1042:1047	R. gnavus	1039:1047	R. gnavus	1039:1047	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	2	65	theme	bromii	451:456	arg1	L2-63					458:462	R. bromii L2-63	448:462	R. bromii L2-63	448:462	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	2	65	theme	bromii	451:456	arg1	species					476:482	a keystone species	465:482	a keystone species for the degradation of resistant starch (RS) in human colon	465:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	5	66	theme	fermentation	1281:1292	arg1	end-products					1294:1305	main fermentation end-products	1276:1305	main fermentation end-products	1276:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	1	67	theme	human	180:184	arg1	microbiota					190:199	the human gut microbiota	176:199	the human gut microbiota	176:199	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	7	68	theme	-dependent	1826:1835	arg1	biosynthesis					1848:1859	vitamin B12 (VitB12)-dependent methionine biosynthesis	1806:1859	vitamin B12 (VitB12)-dependent methionine biosynthesis	1806:1859	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	5	69	from	malto-oligosaccharides	1163:1184	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	7	70	theme	gnavus	1975:1980	arg1	presence					1960:1967	the presence	1956:1967	the presence of R. gnavus	1956:1980	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	1	71	theme	microbiota	190:199	arg1	composition					161:171	the composition	157:171	the composition of the human gut microbiota	157:199	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	8	72	theme	direct	2012:2017	arg1	competition					2019:2029	a direct competition	2010:2029	a direct competition between R. bromii and R. gnavus	2010:2061	Together this study showed a direct competition between R. bromii and R. gnavus on RS, suggesting that in vivo, the R. gnavus population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
30455672	8	73	theme	non-digestible	2181:2194	arg1	carbohydrates					2196:2208	non-digestible carbohydrates	2181:2208	non-digestible carbohydrates reaching the colon such as RS	2181:2238	Together this study showed a direct competition between R. bromii and R. gnavus on RS, suggesting that in vivo, the R. gnavus population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
30455672	5	74	dep	showed	1105:1110	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	5	75	from	glucose	1151:1157	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	1	76	theme	keystone	206:213	arg1	species					238:244	keystone carbohydrate-degrading species	206:244	keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities	206:339	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	4	77	theme	metabolite	866:875	arg1	production					877:886	metabolite production	866:886	metabolite production (1H NMR analysis)	866:904	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	77	theme	metabolite	866:875	arg1	analysis					896:903	1H NMR analysis	889:903	1H NMR analysis	889:903	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	6	78	from	analysis	1332:1339	arg1	starch					1354:1359	starch	1354:1359	starch (SS and RS)	1354:1371	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	6	79	theme	transcriptional	1440:1454	arg1	response					1456:1463	R. gnavus transcriptional response	1430:1463	R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase	1430:1579	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	5	80	theme	transient	1141:1149	arg1	glucose					1151:1157	transient glucose	1141:1157	transient glucose	1141:1157	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	6	81	theme	R.	1430:1431	arg1	response					1456:1463	R. gnavus transcriptional response	1430:1463	R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase	1430:1579	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	2	82	theme	human	532:536	arg1	colon					538:542	human colon	532:542	human colon	532:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	2	83	from	starch	517:522	arg1	colon					538:542	human colon	532:542	human colon	532:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	3	84	theme	R.	752:753	arg1	bromii					755:760	R. bromii	752:760	R. bromii	752:760	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	3	85	theme	mucin	783:787	arg1	degradation					789:799	mucin degradation	783:799	mucin degradation by R. gnavus	783:812	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	4	86	theme	1H	889:890	arg1	production					877:886	metabolite production	866:886	metabolite production (1H NMR analysis)	866:904	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	86	theme	1H	889:890	arg1	analysis					896:903	1H NMR analysis	889:903	1H NMR analysis	889:903	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	6	87	theme	R.	1610:1611	arg1	ability					1599:1605	the ability	1595:1605	the ability of R. gnavus to utilize R. bromii starch degradation products	1595:1667	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	3	88	dep	R.	605:606	arg1	gnavus					608:613	R. gnavus	605:613	R. gnavus	605:613	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	5	89	theme	R.	1117:1118	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	6	90	theme	bromii	1404:1409	arg1	presence					1389:1396	the presence	1385:1396	the presence of R. bromii	1385:1409	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	2	91	theme	keystone	467:474	arg1	L2-63					458:462	R. bromii L2-63	448:462	R. bromii L2-63	448:462	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	2	91	theme	keystone	467:474	arg1	species					476:482	a keystone species	465:482	a keystone species for the degradation of resistant starch (RS) in human colon	465:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	1	92	dep	structure	289:297	arg1	the					285:287	the	285:287	the	285:287	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	6	93	with	line	1585:1588	arg1	ability					1599:1605	the ability	1595:1605	the ability of R. gnavus to utilize R. bromii starch degradation products	1595:1667	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	7	94	theme	biosynthesis	1769:1780	arg1	genes					1782:1786	tryptophan (Trp) biosynthesis genes	1752:1786	tryptophan (Trp) biosynthesis genes	1752:1786	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	6	95	dep	R.	1610:1611	arg1	gnavus					1613:1618	R. gnavus	1610:1618	R. gnavus	1610:1618	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	2	96	theme	resistant	507:515	arg1	RS					525:526	RS	525:526	RS	525:526	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	2	96	theme	resistant	507:515	arg1	starch					517:522	resistant starch	507:522	resistant starch (RS) in human colon	507:542	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	6	97	theme	maltose	1491:1497	arg1	transporters					1499:1510	several maltose transporters	1483:1510	several maltose transporters	1483:1510	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	7	98	theme	tryptophan	1752:1761	arg1	genes					1782:1786	tryptophan (Trp) biosynthesis genes	1752:1786	tryptophan (Trp) biosynthesis genes	1752:1786	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	2	99	theme	gut	378:380	arg1	symbionts					382:390	two major human gut symbionts	362:390	two major human gut symbionts	362:390	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	6	100	theme	expression	1321:1330	arg1	DESeq					1342:1346	DESeq 2	1342:1348	DESeq 2	1342:1348	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	6	100	theme	expression	1321:1330	arg1	analysis					1332:1339	Differential expression analysis	1308:1339	Differential expression analysis (DESeq 2) on starch (SS and RS)	1308:1371	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	5	101	from	lactate	1265:1271	arg1	benefits					1127:1134	R. gnavus benefits	1117:1134	R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products	1117:1305	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	7	102	theme	RS	1677:1678	arg1	co-culture					1680:1689	the RS co-culture	1673:1689	the RS co-culture	1673:1689	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	6	103	theme	starch	1641:1646	arg1	products					1660:1667	R. bromii starch degradation products	1631:1667	R. bromii starch degradation products	1631:1667	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	5	104	theme	R.	1198:1199	arg1	bromii					1201:1206	R. bromii	1198:1206	R. bromii	1198:1206	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	6	105	theme	R.	1631:1632	arg1	products					1660:1667	R. bromii starch degradation products	1631:1667	R. bromii starch degradation products	1631:1667	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	3	106	theme	R.	605:606	arg1	individual					561:570	individual	561:570	individual	561:570	Using anaerobic individual and co-cultures of R. bromii and R. gnavus grown on mucin or starch as sole carbon source, we showed that starch degradation by R. bromii supported the growth of R. gnavus whereas R. bromii did not benefit from mucin degradation by R. gnavus.
30455672	2	107	theme	mucin-degrader	397:410	arg1	29149					437:441	the mucin-degrader Ruminococcus gnavus ATCC 29149	393:441	the mucin-degrader Ruminococcus gnavus ATCC 29149	393:441	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	0	108	theme	gnavus	60:65	arg1	Cross-Feeding					30:42	the Cross-Feeding	26:42	the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates	26:123	Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates.
30455672	1	109	theme	microbial	319:327	arg1	communities					329:339	gut microbial communities	315:339	gut microbial communities	315:339	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30455672	7	110	theme	significant	1711:1721	arg1	increase					1723:1730	a significant increase	1709:1730	a significant increase in the induction of tryptophan (Trp) biosynthesis genes	1709:1786	In the RS co-culture, R. bromii showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of R. gnavus.
30455672	4	111	theme	bacterial	911:919	arg1	RNA-Seq					947:953	RNA-Seq	947:953	RNA-Seq	947:953	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	4	111	theme	bacterial	911:919	arg1	response					937:944	bacterial transcriptional response	911:944	bacterial transcriptional response (RNA-Seq)	911:954	Further we analyzed the growth (quantitative PCR), metabolite production (1H NMR analysis), and bacterial transcriptional response (RNA-Seq) of R. bromii cultured with RS or soluble starch (SS) in the presence or absence of R. gnavus.
30455672	5	112	theme	producing	1233:1241	arg1	acetate					1243:1249	producing acetate	1233:1249	producing acetate	1233:1249	In co-culture fermentations on starch, 1H NMR analysis showed that R. gnavus benefits from transient glucose and malto-oligosaccharides released by R. bromii upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products.
30455672	8	113	theme	gnavus	2102:2107	arg1	population					2109:2118	the R. gnavus population	2095:2118	the R. gnavus population inhabiting the mucus niche	2095:2145	Together this study showed a direct competition between R. bromii and R. gnavus on RS, suggesting that in vivo, the R. gnavus population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
30455672	6	114	dep	starch	1354:1359	arg1	RS					1369:1370	RS	1369:1370	RS	1369:1370	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	6	114	dep	starch	1354:1359	arg1	SS					1362:1363	SS	1362:1363	SS	1362:1363	Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of R. bromii induced changes in R. gnavus transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of R. gnavus to utilize R. bromii starch degradation products.
30455672	2	115	theme	major	366:370	arg1	symbionts					382:390	two major human gut symbionts	362:390	two major human gut symbionts	362:390	Here, we focused on two major human gut symbionts, the mucin-degrader Ruminococcus gnavus ATCC 29149, and R. bromii L2-63, a keystone species for the degradation of resistant starch (RS) in human colon.
30455672	1	116	theme	critical	256:263	arg1	role					265:268	a critical role	254:268	a critical role	254:268	Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities.
30529121	2	0	theme	acid	442:445	arg1	dimer					447:451	(-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer	403:451	dimer	447:451	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	0	theme	acid	442:445	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	0	1	from	activity	17:24	arg1	cells					72:76	HeLa cells	67:76	HeLa cells	67:76	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	2	2	theme	3-caffeoylquinic	565:580	arg1	acid					582:585	3-caffeoylquinic acid	565:585	3-caffeoylquinic acid	565:585	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	4	3	from	phase	801:805	arg1	termination					766:776	termination	766:776	termination of cell cycle at G0/G1 phase	766:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	3	from	phase	801:805	arg1	apoptosis					752:760	apoptosis	752:760	apoptosis	752:760	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	3	from	phase	801:805	arg1	cells					746:750	HeLa cells	741:750	HeLa cells apoptosis and termination of cell cycle at G0/G1 phase	741:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	5	4	dep	investigations	889:902	arg1	the					863:865	the	863:865	the	863:865	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	4	dep	investigations	889:902	arg1	basis					867:871	basis	867:871	basis	867:871	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	6	5	from	pathway	1127:1133	arg1	cells					1143:1147	HeLa cells	1138:1147	HeLa cells	1138:1147	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	2	6	theme	-epigallocatechin	495:511	arg1	derivatives					513:523	caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives	383:523	caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives	383:523	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	5	7	theme	p53	1073:1075	arg1	expressions					1058:1068	the mRNA expressions	1049:1068	the mRNA expressions of p53 and p21	1049:1083	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	7	8	theme	H.	1325:1326	arg1	polyphenols					1337:1347	H. serotina polyphenols	1325:1347	H. serotina polyphenols	1325:1347	This study might provide a theoretical basis for the application of H. serotina polyphenols as tumor preventive agent.
30529121	2	9	theme	H.	341:342	arg1	serotina					344:351	H. serotina	341:351	H. serotina (HSP)	341:357	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	9	theme	H.	341:342	arg1	HSP					354:356	HSP	354:356	HSP	354:356	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	5	10	theme	mRNA	1053:1056	arg1	expressions					1058:1068	the mRNA expressions	1049:1068	the mRNA expressions of p53 and p21	1049:1083	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	1	11	theme	polyphenols	235:245	arg1	origin					225:230	a good origin	218:230	not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches	160:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	1	11	theme	polyphenols	235:245	arg1	source					183:188	one important source	169:188	not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches	160:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	0	12	theme	cell	95:98	arg1	apoptosis					100:108	cell apoptosis	95:108	cell apoptosis	95:108	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	6	13	theme	HeLa	1138:1141	arg1	cells					1143:1147	HeLa cells	1138:1147	HeLa cells	1138:1147	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	6	14	theme	cytochrome	1197:1206	arg1	Bax					1192:1194	Bax	1192:1194	Bax	1192:1194	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	6	14	theme	cytochrome	1197:1206	arg1	c					1208:1208	cytochrome c	1197:1208	cytochrome c	1197:1208	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	5	15	theme	related	986:992	arg1	D1					1017:1018	cyclin D1	1010:1018	cyclin D1	1010:1018	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	15	theme	related	986:992	arg1	Cdk4					1030:1033	Cdk4	1030:1033	Cdk4	1030:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	15	theme	related	986:992	arg1	Ckd2					1021:1024	Ckd2	1021:1024	Ckd2	1021:1024	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	15	theme	related	986:992	arg1	genes					994:998	cell cycle related genes	975:998	cell cycle related genes including cyclin D1, Ckd2 and Cdk4	975:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	6	16	theme	apoptosis	1117:1125	arg1	pathway					1127:1133	the mitochondrial apoptosis pathway	1099:1133	the mitochondrial apoptosis pathway in HeLa cells	1099:1147	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	5	17	theme	mechanism	921:929	arg1	investigations					889:902	the expanded investigations	876:902	the expanded investigations of anti-neoplasm mechanism	876:929	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	4	18	dep	cells	746:750	arg1	termination					766:776	termination	766:776	termination of cell cycle at G0/G1 phase	766:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	18	dep	cells	746:750	arg1	apoptosis					752:760	apoptosis	752:760	apoptosis	752:760	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	18	dep	cells	746:750	arg1	cells					746:750	HeLa cells	741:750	HeLa cells apoptosis and termination of cell cycle at G0/G1 phase	741:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	2	19	theme	catechin	545:552	arg1	trimer					554:559	catechin trimer	545:559	catechin trimer	545:559	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	6	20	theme	mitochondrial	1103:1115	arg1	pathway					1127:1133	the mitochondrial apoptosis pathway	1099:1133	the mitochondrial apoptosis pathway in HeLa cells	1099:1147	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	1	21	theme	antineoplastic	252:265	arg1	functions					267:275	antineoplastic functions	252:275	antineoplastic functions in non-clinical researches	252:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	6	22	theme	Bax	1192:1194	arg1	inhibition					1236:1245	inhibition	1236:1245	activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2	1178:1254	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	6	22	theme	Bax	1192:1194	arg1	activation					1178:1187	activation	1178:1187	activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2	1178:1254	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	4	23	theme	cells	746:750	arg1	induction					728:736	induction	728:736	induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase	728:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	24	theme	anti-tumor	832:841	arg1	activity					843:850	the anti-tumor activity	828:850	the anti-tumor activity of HSP	828:857	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	0	25	theme	apoptosis	100:108	arg1	induction					82:90	induction	82:90	induction of cell apoptosis and cell cycle arrest	82:130	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	3	26	theme	ROS	684:686	arg1	accumulation					688:699	intracellular ROS accumulation	670:699	intracellular ROS accumulation	670:699	HSP significantly inhibited the proliferation of HeLa cells in vitro, and induced intracellular ROS accumulation.
30529121	2	27	from	serotina	344:351	arg1	polyphenols					324:334	the polyphenols	320:334	the polyphenols from H. serotina (HSP)	320:357	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	4	28	theme	HeLa	741:744	arg1	termination					766:776	termination	766:776	termination of cell cycle at G0/G1 phase	766:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	28	theme	HeLa	741:744	arg1	apoptosis					752:760	apoptosis	752:760	apoptosis	752:760	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	28	theme	HeLa	741:744	arg1	cells					746:750	HeLa cells	741:750	HeLa cells apoptosis and termination of cell cycle at G0/G1 phase	741:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	7	29	theme	preventive	1358:1367	arg1	agent					1369:1373	tumor preventive agent	1352:1373	tumor preventive agent	1352:1373	This study might provide a theoretical basis for the application of H. serotina polyphenols as tumor preventive agent.
30529121	0	30	theme	cytotoxicity	4:15	arg1	activity					17:24	The cytotoxicity activity	0:24	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.	0:131	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	2	31	theme	-gallic	434:440	arg1	dimer					447:451	(-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer	403:451	dimer	447:451	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	31	theme	-gallic	434:440	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	1	32	from	functions	267:275	arg1	researches					293:302	non-clinical researches	280:302	non-clinical researches	280:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	2	33	theme	-	404:404	arg1	dimer					447:451	(-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer	403:451	dimer	447:451	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	33	theme	-	404:404	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	6	34	theme	Bcl-2	1250:1254	arg1	inhibition					1236:1245	inhibition	1236:1245	activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2	1178:1254	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	6	34	theme	Bcl-2	1250:1254	arg1	activation					1178:1187	activation	1178:1187	activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2	1178:1254	In addition, the mitochondrial apoptosis pathway in HeLa cells was initiated by HSP through activation of Bax, cytochrome c and Caspase-3, as well as inhibition of Bcl-2.
30529121	1	35	theme	important	173:181	arg1	source					183:188	one important source	169:188	not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches	160:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	0	36	theme	cycle	119:123	arg1	arrest					125:130	cell cycle arrest	114:130	cell cycle arrest	114:130	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	5	37	theme	genes	994:998	arg1	expressions					960:970	the mRNA expressions	951:970	the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4	951:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	38	theme	anti-neoplasm	907:919	arg1	mechanism					921:929	anti-neoplasm mechanism	907:929	anti-neoplasm mechanism	907:929	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	39	theme	cell	975:978	arg1	D1					1017:1018	cyclin D1	1010:1018	cyclin D1	1010:1018	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	39	theme	cell	975:978	arg1	Cdk4					1030:1033	Cdk4	1030:1033	Cdk4	1030:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	39	theme	cell	975:978	arg1	Ckd2					1021:1024	Ckd2	1021:1024	Ckd2	1021:1024	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	39	theme	cell	975:978	arg1	genes					994:998	cell cycle related genes	975:998	cell cycle related genes including cyclin D1, Ckd2 and Cdk4	975:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	1	40	theme	non-clinical	280:291	arg1	researches					293:302	non-clinical researches	280:302	non-clinical researches	280:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	0	41	theme	cell	114:117	arg1	arrest					125:130	cell cycle arrest	114:130	cell cycle arrest	114:130	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	2	42	theme	3'-o-methyl	422:432	arg1	dimer					447:451	(-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer	403:451	dimer	447:451	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	42	theme	3'-o-methyl	422:432	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	43	theme	acid	391:394	arg1	dimer					447:451	(-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer	403:451	dimer	447:451	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	43	theme	acid	391:394	arg1	hexoside					482:489	quercetin-acetyl-rutinoside hexoside	454:489	quercetin-acetyl-rutinoside hexoside	454:489	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	43	theme	acid	391:394	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	0	44	theme	serotina	43:50	arg1	polyphenols					52:62	Hohenbuehelia serotina polyphenols	29:62	Hohenbuehelia serotina polyphenols	29:62	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	2	45	theme	caffeic	383:389	arg1	dimer					447:451	(-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer	403:451	dimer	447:451	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	45	theme	caffeic	383:389	arg1	hexoside					482:489	quercetin-acetyl-rutinoside hexoside	454:489	quercetin-acetyl-rutinoside hexoside	454:489	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	45	theme	caffeic	383:389	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	4	46	theme	cycle	786:790	arg1	termination					766:776	termination	766:776	termination of cell cycle at G0/G1 phase	766:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	46	theme	cycle	786:790	arg1	apoptosis					752:760	apoptosis	752:760	apoptosis	752:760	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	4	46	theme	cycle	786:790	arg1	cells					746:750	HeLa cells	741:750	HeLa cells apoptosis and termination of cell cycle at G0/G1 phase	741:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	1	47	theme	polysaccharides	193:207	arg1	origin					225:230	a good origin	218:230	not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches	160:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	1	47	theme	polysaccharides	193:207	arg1	source					183:188	one important source	169:188	not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches	160:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	0	48	theme	Hohenbuehelia	29:41	arg1	polyphenols					52:62	Hohenbuehelia serotina polyphenols	29:62	Hohenbuehelia serotina polyphenols	29:62	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	5	49	theme	p21	1081:1083	arg1	expressions					1058:1068	the mRNA expressions	1049:1068	the mRNA expressions of p53 and p21	1049:1083	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	0	50	theme	arrest	125:130	arg1	induction					82:90	induction	82:90	induction of cell apoptosis and cell cycle arrest	82:130	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	4	51	theme	cell	781:784	arg1	cycle					786:790	cell cycle	781:790	cell cycle	781:790	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	2	52	theme	quercetin-acetyl-rutinoside	454:480	arg1	hexoside					482:489	quercetin-acetyl-rutinoside hexoside	454:489	quercetin-acetyl-rutinoside hexoside	454:489	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	52	theme	quercetin-acetyl-rutinoside	454:480	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	4	53	theme	G0/G1	795:799	arg1	phase					801:805	G0/G1 phase	795:805	G0/G1 phase	795:805	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	7	54	theme	tumor	1352:1356	arg1	agent					1369:1373	tumor preventive agent	1352:1373	tumor preventive agent	1352:1373	This study might provide a theoretical basis for the application of H. serotina polyphenols as tumor preventive agent.
30529121	0	55	theme	polyphenols	52:62	arg1	activity					17:24	The cytotoxicity activity	0:24	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.	0:131	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	4	56	theme	HSP	855:857	arg1	activity					843:850	the anti-tumor activity	828:850	the anti-tumor activity of HSP	828:857	It was also observed that induction of HeLa cells apoptosis and termination of cell cycle at G0/G1 phase were associated with the anti-tumor activity of HSP.
30529121	2	57	theme	-epicatechin-3-	406:420	arg1	dimer					447:451	(-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer	403:451	dimer	447:451	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	2	57	theme	-epicatechin-3-	406:420	arg1	dimer					396:400	caffeic acid dimer	383:400	caffeic acid dimer	383:400	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	5	58	theme	cyclin	1010:1015	arg1	D1					1017:1018	cyclin D1	1010:1018	cyclin D1	1010:1018	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	7	59	theme	polyphenols	1337:1347	arg1	application					1310:1320	the application	1306:1320	the application of H. serotina polyphenols	1306:1347	This study might provide a theoretical basis for the application of H. serotina polyphenols as tumor preventive agent.
30529121	2	60	theme	rutin	526:530	arg1	derivatives					532:542	rutin derivatives	526:542	rutin derivatives	526:542	In this study, the polyphenols from H. serotina (HSP) were mainly composed by caffeic acid dimer, (-)-epicatechin-3-(3'-o-methyl)-gallic acid dimer, quercetin-acetyl-rutinoside hexoside, (-)-epigallocatechin derivatives, rutin derivatives, catechin trimer and 3-caffeoylquinic acid.
30529121	5	61	theme	cycle	980:984	arg1	D1					1017:1018	cyclin D1	1010:1018	cyclin D1	1010:1018	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	61	theme	cycle	980:984	arg1	Cdk4					1030:1033	Cdk4	1030:1033	Cdk4	1030:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	61	theme	cycle	980:984	arg1	Ckd2					1021:1024	Ckd2	1021:1024	Ckd2	1021:1024	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	61	theme	cycle	980:984	arg1	genes					994:998	cell cycle related genes	975:998	cell cycle related genes including cyclin D1, Ckd2 and Cdk4	975:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	1	62	with	polyphenols	235:245	arg1	functions					267:275	antineoplastic functions	252:275	antineoplastic functions in non-clinical researches	252:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	7	63	theme	theoretical	1284:1294	arg1	basis					1296:1300	a theoretical basis	1282:1300	a theoretical basis for the application of H. serotina polyphenols	1282:1347	This study might provide a theoretical basis for the application of H. serotina polyphenols as tumor preventive agent.
30529121	7	64	theme	serotina	1328:1335	arg1	polyphenols					1337:1347	H. serotina polyphenols	1325:1347	H. serotina polyphenols	1325:1347	This study might provide a theoretical basis for the application of H. serotina polyphenols as tumor preventive agent.
30529121	3	65	theme	HeLa	637:640	arg1	cells					642:646	HeLa cells	637:646	HeLa cells	637:646	HSP significantly inhibited the proliferation of HeLa cells in vitro, and induced intracellular ROS accumulation.
30529121	5	66	theme	mRNA	955:958	arg1	expressions					960:970	the mRNA expressions	951:970	the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4	951:1033	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	5	67	theme	expanded	880:887	arg1	investigations					889:902	the expanded investigations	876:902	the expanded investigations of anti-neoplasm mechanism	876:929	On the basis of the expanded investigations of anti-neoplasm mechanism, HSP could decrease the mRNA expressions of cell cycle related genes including cyclin D1, Ckd2 and Cdk4, and increase the mRNA expressions of p53 and p21.
30529121	3	68	theme	cells	642:646	arg1	proliferation					620:632	the proliferation	616:632	the proliferation of HeLa cells	616:646	HSP significantly inhibited the proliferation of HeLa cells in vitro, and induced intracellular ROS accumulation.
30529121	1	69	theme	Hohenbuehelia	133:145	arg1	serotina					147:154	Hohenbuehelia serotina	133:154	Hohenbuehelia serotina	133:154	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	1	70	theme	good	220:223	arg1	origin					225:230	a good origin	218:230	not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches	160:302	Hohenbuehelia serotina, is not only one important source of polysaccharides but also a good origin of polyphenols with antineoplastic functions in non-clinical researches.
30529121	0	71	theme	HeLa	67:70	arg1	cells					72:76	HeLa cells	67:76	HeLa cells	67:76	The cytotoxicity activity of Hohenbuehelia serotina polyphenols on HeLa cells via induction of cell apoptosis and cell cycle arrest.
30529121	3	72	theme	intracellular	670:682	arg1	accumulation					688:699	intracellular ROS accumulation	670:699	intracellular ROS accumulation	670:699	HSP significantly inhibited the proliferation of HeLa cells in vitro, and induced intracellular ROS accumulation.
31126510	5	0	theme	acid	545:548	arg1	products					560:567	hydroxycinnamic acid oxidation products	529:567	hydroxycinnamic acid oxidation products	529:567	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	7	1	theme	relevant	1098:1105	arg1	polyphenols					1055:1065	the available polyphenols	1041:1065	the available polyphenols	1041:1065	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	2	2	with	extractions	284:294	arg1	solutions					317:325	aqueous/organic solutions	301:325	aqueous/organic solutions	301:325	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	2	3	theme	apple	169:173	arg1	pomace					175:180	apple pomace	169:180	apple pomace	169:180	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	5	4	theme	non-extractable	605:619	arg1	procyanidins					630:641	non-extractable oxidised procyanidins	605:641	non-extractable oxidised procyanidins that represented more than 4-fold	605:675	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	1	5	theme	Hot	54:56	arg1	process					91:97	an easily implementable process	67:97	an easily implementable process for polyphenols extraction	67:124	Hot water is an easily implementable process for polyphenols extraction.
31126510	1	5	theme	Hot	54:56	arg1	water					58:62	Hot water	54:62	Hot water	54:62	Hot water is an easily implementable process for polyphenols extraction.
31126510	6	6	theme	superheated-water	741:757	arg1	extraction					759:768	Microwave superheated-water extraction	731:768	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions	731:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	5	7	theme	oxidised	621:628	arg1	procyanidins					630:641	non-extractable oxidised procyanidins	605:641	non-extractable oxidised procyanidins that represented more than 4-fold	605:675	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	6	8	theme	Microwave	731:739	arg1	extraction					759:768	Microwave superheated-water extraction	731:768	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions	731:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	5	9	from	pomace	723:728	arg1	polyphenols					704:714	native apple polyphenols	691:714	native apple polyphenols in the pomace	691:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	5	9	from	pomace	723:728	arg1	amount					681:686	the amount	677:686	the amount of native apple polyphenols in the pomace	677:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	7	10	from	%	1036:1036	arg1	pomace					1078:1083	apple pomace	1072:1083	apple pomace	1072:1083	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	0	11	theme	polyphenols	41:51	arg1	chemistry					15:23	the chemistry	11:23	the chemistry of apple pomace polyphenols	11:51	Revisiting the chemistry of apple pomace polyphenols.
31126510	4	12	theme	other	474:478	arg1	classes					480:486	the other classes	470:486	the other classes	470:486	Their amount decreased 50% after hot water extraction, while the other classes remained unchanged.
31126510	2	13	theme	water	254:258	arg1	extraction					260:269	hot water extraction	250:269	hot water extraction	250:269	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	3	14	theme	main	378:381	arg1	polyphenols					396:406	the main apple native polyphenols	374:406	the main apple native polyphenols	374:406	As determined by UHPLC-DAD, flavan-3-ols were the main apple native polyphenols.
31126510	3	14	theme	main	378:381	arg1	flavan-3-ols					356:367	flavan-3-ols	356:367	flavan-3-ols	356:367	As determined by UHPLC-DAD, flavan-3-ols were the main apple native polyphenols.
31126510	2	15	theme	aqueous/organic	301:315	arg1	solutions					317:325	aqueous/organic solutions	301:325	aqueous/organic solutions	301:325	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	3	16	theme	apple	383:387	arg1	polyphenols					396:406	the main apple native polyphenols	374:406	the main apple native polyphenols	374:406	As determined by UHPLC-DAD, flavan-3-ols were the main apple native polyphenols.
31126510	3	16	theme	apple	383:387	arg1	flavan-3-ols					356:367	flavan-3-ols	356:367	flavan-3-ols	356:367	As determined by UHPLC-DAD, flavan-3-ols were the main apple native polyphenols.
31126510	6	17	theme	water/acetone	809:821	arg1	solutions					823:831	water/acetone solutions	809:831	water/acetone solutions	809:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	1	18	theme	implementable	77:89	arg1	process					91:97	an easily implementable process	67:97	an easily implementable process for polyphenols extraction	67:124	Hot water is an easily implementable process for polyphenols extraction.
31126510	1	18	theme	implementable	77:89	arg1	water					58:62	Hot water	54:62	Hot water	54:62	Hot water is an easily implementable process for polyphenols extraction.
31126510	6	19	from	amounts	846:852	arg1	solutions					823:831	water/acetone solutions	809:831	water/acetone solutions	809:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	20	attach	linked	973:978	arg1	polysaccharides					983:997	polysaccharides	983:997	polysaccharides	983:997	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	20	attach	linked	973:978	arg2	procyanidins					940:951	oxidised procyanidins	931:951	oxidised procyanidins	931:951	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	21	from	solutions	906:914	arg1	insoluble					879:887	insoluble	879:887	insoluble	879:887	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	7	22	theme	apple	1072:1076	arg1	pomace					1078:1083	apple pomace	1072:1083	apple pomace	1072:1083	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	7	23	theme	polyphenols	1055:1065	arg1	%					1036:1036	up to 40%	1028:1036	up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation	1028:1135	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	7	23	theme	polyphenols	1055:1065	arg1	polyphenols					1055:1065	the available polyphenols	1041:1065	the available polyphenols	1041:1065	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	4	24	theme	hot	442:444	arg1	extraction					452:461	hot water extraction	442:461	hot water extraction	442:461	Their amount decreased 50% after hot water extraction, while the other classes remained unchanged.
31126510	6	25	theme	high	841:844	arg1	polyphenols					857:867	polyphenols	857:867	polyphenols that were insoluble in water/ethanol solutions	857:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	25	theme	high	841:844	arg1	amounts					846:852	the high amounts	837:852	the high amounts of polyphenols that were insoluble in water/ethanol solutions	837:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	0	26	theme	pomace	34:39	arg1	polyphenols					41:51	apple pomace polyphenols	28:51	apple pomace polyphenols	28:51	Revisiting the chemistry of apple pomace polyphenols.
31126510	6	27	theme	oxidised	931:938	arg1	procyanidins					940:951	oxidised procyanidins	931:951	oxidised procyanidins	931:951	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	7	28	theme	agro-food	1111:1119	arg1	valuation					1127:1135	agro-food waste valuation	1111:1135	agro-food waste valuation	1111:1135	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	2	29	dep	assessed	224:231	arg1	followed					272:279	followed	272:279	followed by extractions with aqueous/organic solutions	272:325	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	0	30	theme	apple	28:32	arg1	polyphenols					41:51	apple pomace polyphenols	28:51	apple pomace polyphenols	28:51	Revisiting the chemistry of apple pomace polyphenols.
31126510	5	31	from	amount	681:686	arg1	pomace					723:728	the pomace	719:728	the pomace	719:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	7	32	theme	waste	1121:1125	arg1	valuation					1127:1135	agro-food waste valuation	1111:1135	agro-food waste valuation	1111:1135	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	2	33	theme	process	158:164	arg1	effect					143:148	the effect	139:148	the effect of this process on apple pomace	139:180	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	5	34	theme	oxidation	550:558	arg1	products					560:567	hydroxycinnamic acid oxidation products	529:567	hydroxycinnamic acid oxidation products	529:567	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	6	35	from	solutions	823:831	arg1	extraction					759:768	Microwave superheated-water extraction	731:768	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions	731:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	3	36	theme	native	389:394	arg1	polyphenols					396:406	the main apple native polyphenols	374:406	the main apple native polyphenols	374:406	As determined by UHPLC-DAD, flavan-3-ols were the main apple native polyphenols.
31126510	3	36	theme	native	389:394	arg1	flavan-3-ols					356:367	flavan-3-ols	356:367	flavan-3-ols	356:367	As determined by UHPLC-DAD, flavan-3-ols were the main apple native polyphenols.
31126510	5	37	theme	native	691:696	arg1	polyphenols					704:714	native apple polyphenols	691:714	native apple polyphenols in the pomace	691:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	4	38	theme	water	446:450	arg1	extraction					452:461	hot water extraction	442:461	hot water extraction	442:461	Their amount decreased 50% after hot water extraction, while the other classes remained unchanged.
31126510	6	39	theme	wall	792:795	arg1	material					797:804	the insoluble cell wall material	773:804	the insoluble cell wall material in water/acetone solutions	773:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	1	40	theme	polyphenols	103:113	arg1	extraction					115:124	polyphenols extraction	103:124	polyphenols extraction	103:124	Hot water is an easily implementable process for polyphenols extraction.
31126510	2	41	from	effect	143:148	arg1	pomace					175:180	apple pomace	169:180	apple pomace	169:180	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	5	42	theme	apple	698:702	arg1	polyphenols					704:714	native apple polyphenols	691:714	native apple polyphenols in the pomace	691:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	2	43	theme	overall	187:193	arg1	composition					208:218	the overall polyphenolic composition	183:218	the overall polyphenolic composition	183:218	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	2	44	theme	polyphenolic	195:206	arg1	composition					208:218	the overall polyphenolic composition	183:218	the overall polyphenolic composition	183:218	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	6	45	theme	cell	787:790	arg1	material					797:804	the insoluble cell wall material	773:804	the insoluble cell wall material in water/acetone solutions	773:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	46	theme	water/ethanol	892:904	arg1	solutions					906:914	water/ethanol solutions	892:914	water/ethanol solutions	892:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	5	47	theme	polyphenols	704:714	arg1	polyphenols					704:714	native apple polyphenols	691:714	native apple polyphenols in the pomace	691:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	5	47	theme	polyphenols	704:714	arg1	amount					681:686	the amount	677:686	the amount of native apple polyphenols in the pomace	677:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	2	48	theme	hot	250:252	arg1	extraction					260:269	hot water extraction	250:269	hot water extraction	250:269	To evaluate the effect of this process on apple pomace, the overall polyphenolic composition was assessed before and after hot water extraction, followed by extractions with aqueous/organic solutions.
31126510	6	49	theme	amounts	846:852	arg1	extraction					759:768	Microwave superheated-water extraction	731:768	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions	731:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	50	from	material	797:804	arg1	solutions					823:831	water/acetone solutions	809:831	water/acetone solutions	809:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	5	51	from	polyphenols	704:714	arg1	pomace					723:728	the pomace	719:728	the pomace	719:728	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31126510	6	52	theme	insoluble	777:785	arg1	material					797:804	the insoluble cell wall material	773:804	the insoluble cell wall material in water/acetone solutions	773:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	53	theme	material	797:804	arg1	extraction					759:768	Microwave superheated-water extraction	731:768	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions	731:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	54	theme	polyphenols	857:867	arg1	polyphenols					857:867	polyphenols	857:867	polyphenols that were insoluble in water/ethanol solutions	857:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	54	theme	polyphenols	857:867	arg1	amounts					846:852	the high amounts	837:852	the high amounts of polyphenols that were insoluble in water/ethanol solutions	837:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	6	54	theme	polyphenols	857:867	arg1	material					797:804	the insoluble cell wall material	773:804	the insoluble cell wall material in water/acetone solutions	773:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	7	55	theme	available	1045:1053	arg1	polyphenols					1055:1065	the available polyphenols	1041:1065	the available polyphenols	1041:1065	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	6	56	from	extraction	759:768	arg1	solutions					823:831	water/acetone solutions	809:831	water/acetone solutions	809:831	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	7	57	dep	40	1034:1035	arg1	to					1031:1032	to	1031:1032	to	1031:1032	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	6	58	from	insoluble	879:887	arg1	solutions					906:914	water/ethanol solutions	892:914	water/ethanol solutions	892:914	Microwave superheated-water extraction of the insoluble cell wall material in water/acetone solutions and the high amounts of polyphenols that were insoluble in water/ethanol solutions suggested that oxidised procyanidins could be covalently linked to polysaccharides.
31126510	7	59	from	pomace	1078:1083	arg1	%					1036:1036	up to 40%	1028:1036	up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation	1028:1135	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	7	59	from	pomace	1078:1083	arg1	polyphenols					1055:1065	the available polyphenols	1041:1065	the available polyphenols	1041:1065	These complexes represented up to 40% of the available polyphenols from apple pomace, potentially relevant for agro-food waste valuation.
31126510	5	60	theme	hydroxycinnamic	529:543	arg1	products					560:567	hydroxycinnamic acid oxidation products	529:567	hydroxycinnamic acid oxidation products	529:567	Dihydrochalcones and hydroxycinnamic acid oxidation products, were also observed, alongside with non-extractable oxidised procyanidins that represented more than 4-fold the amount of native apple polyphenols in the pomace.
31102858	8	0	theme	various	1674:1680	arg1	environments					1682:1693	various environments	1674:1693	various environments	1674:1693	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
31102858	5	1	dep	biofilms	818:825	arg1	region					851:856	especially the biofilm region	828:856	especially the biofilm region closer to electrode surface	828:884	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	1	2	theme	transfer	168:175	arg1	efficiency					183:192	The extracellular electron transfer (EET) efficiency	141:192	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems	141:222	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	1	2	theme	transfer	168:175	arg1	dependent					246:254	dependent	246:254	dependent	246:254	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	8	3	theme	biofilms	1759:1766	arg1	activity					1741:1748	electrochemical activity	1725:1748	electrochemical activity of anode biofilms	1725:1766	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
31102858	5	4	theme	facilitated	1096:1106	arg1	EET					1108:1110	EPS and consequently facilitated EET	1075:1110	EPS and consequently facilitated EET	1075:1110	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	2	5	theme	EET	354:356	arg1	conduit					358:364	EET conduit	354:364	EET conduit	354:364	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	1	6	theme	anode	259:263	arg1	potentials					265:274	anode potentials	259:274	anode potentials	259:274	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	6	7	theme	extracellular	1151:1163	arg1	layers					1199:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	6	8	theme	direct	1272:1277	arg1	EET					1279:1281	limited direct EET	1264:1281	limited direct EET	1264:1281	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	2	9	theme	underlying	292:301	arg1	mechanism					303:311	the underlying mechanism	288:311	the underlying mechanism	288:311	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	7	10	theme	different	1468:1476	arg1	potentials					1484:1493	different anode potentials	1468:1493	different anode potentials	1468:1493	These results demonstrated that the production of EPS under different anode potentials might be finely regulated by cells to keep balance between EET efficiency and cell-protection.
31102858	0	11	theme	spatial	84:90	arg1	structure					92:100	spatial structure	84:100	spatial structure	84:100	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	5	12	theme	extracellular	979:991	arg1	polysaccharides					993:1007	extracellular polysaccharides	979:1007	extracellular polysaccharides	979:1007	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	4	13	theme	soli	708:711	arg1	biofilms					713:720	Geobacter soli biofilms	698:720	Geobacter soli biofilms	698:720	The electrochemical activities and cell viabilities of Geobacter soli biofilms were simultaneously attenuated at 0.4 and 0.6 V compared to -0.2 and 0 V.
31102858	5	14	theme	closer	858:863	arg1	region					851:856	especially the biofilm region	828:856	especially the biofilm region closer to electrode surface	828:884	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	0	15	theme	extracellular	105:117	arg1	substances					129:138	extracellular polymeric substances	105:138	extracellular polymeric substances	105:138	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	5	16	theme	redox-active	948:959	arg1	proteins					961:968	relatively more extracellular redox-active proteins	918:968	relatively more extracellular redox-active proteins	918:968	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	5	17	theme	electrode	868:876	arg1	surface					878:884	electrode surface	868:884	electrode surface	868:884	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	1	18	theme	EET	178:180	arg1	efficiency					183:192	The extracellular electron transfer (EET) efficiency	141:192	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems	141:222	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	1	18	theme	EET	178:180	arg1	dependent					246:254	dependent	246:254	dependent	246:254	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	8	19	theme	new	1612:1614	arg1	insight					1616:1622	a new insight	1610:1622	a new insight to investigate the Geobacter biofilms coping with various environments	1610:1693	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
31102858	0	20	theme	Anode	0:4	arg1	potentials					6:15	Anode potentials	0:15	Anode potentials	0:15	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	4	21	theme	electrochemical	647:661	arg1	activities					663:672	electrochemical activities	647:672	electrochemical activities	647:672	The electrochemical activities and cell viabilities of Geobacter soli biofilms were simultaneously attenuated at 0.4 and 0.6 V compared to -0.2 and 0 V.
31102858	5	22	theme	extracellular	934:946	arg1	proteins					961:968	relatively more extracellular redox-active proteins	918:968	relatively more extracellular redox-active proteins	918:968	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	4	23	theme	cell	678:681	arg1	viabilities					683:693	cell viabilities	678:693	cell viabilities	678:693	The electrochemical activities and cell viabilities of Geobacter soli biofilms were simultaneously attenuated at 0.4 and 0.6 V compared to -0.2 and 0 V.
31102858	2	24	theme	substances	450:459	arg1	role					418:421	the role	414:421	the role of extracellular polymeric substances (EPS) surrounding electroactive cells	414:497	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	6	25	theme	limited	1264:1270	arg1	EET					1279:1281	limited direct EET	1264:1281	limited direct EET	1264:1281	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	6	26	theme	physical	1302:1309	arg1	barriers					1311:1318	physical barriers	1302:1318	physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes	1302:1405	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	0	27	dep	composition	68:78	arg1	the					64:66	the	64:66	the	64:66	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	0	28	theme	Geobacter	26:34	arg1	insights					50:57	Geobacter biofilms: New insights	26:57	Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances	26:138	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	5	29	theme	higher	1026:1031	arg1	capacities					1061:1070	higher electron accepting/donating capacities	1026:1070	higher electron accepting/donating capacities	1026:1070	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	0	30	theme	substances	129:138	arg1	composition					68:78	composition	68:78	composition	68:78	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	0	30	theme	substances	129:138	arg1	structure					92:100	spatial structure	84:100	spatial structure	84:100	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	3	31	theme	anode	553:557	arg1	potentials					559:568	anode potentials	553:568	anode potentials	553:568	In this study, the response of Geobacter biofilms to anode potentials was investigated with a special emphasis on the mechanistic role of EPS.
31102858	5	32	theme	accepting/donating	1042:1059	arg1	capacities					1061:1070	higher electron accepting/donating capacities	1026:1070	higher electron accepting/donating capacities	1026:1070	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	1	33	theme	bioelectrochemical	197:214	arg1	systems					216:222	bioelectrochemical systems	197:222	bioelectrochemical systems	197:222	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	2	34	theme	previous	314:321	arg1	studies					323:329	previous studies	314:329	previous studies	314:329	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	0	35	theme	polymeric	119:127	arg1	substances					129:138	extracellular polymeric substances	105:138	extracellular polymeric substances	105:138	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	4	36	theme	Geobacter	698:706	arg1	biofilms					713:720	Geobacter soli biofilms	698:720	Geobacter soli biofilms	698:720	The electrochemical activities and cell viabilities of Geobacter soli biofilms were simultaneously attenuated at 0.4 and 0.6 V compared to -0.2 and 0 V.
31102858	7	37	theme	anode	1478:1482	arg1	potentials					1484:1493	different anode potentials	1468:1493	different anode potentials	1468:1493	These results demonstrated that the production of EPS under different anode potentials might be finely regulated by cells to keep balance between EET efficiency and cell-protection.
31102858	1	38	theme	extracellular	145:157	arg1	efficiency					183:192	The extracellular electron transfer (EET) efficiency	141:192	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems	141:222	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	1	38	theme	extracellular	145:157	arg1	dependent					246:254	dependent	246:254	dependent	246:254	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	2	39	theme	electroactive	479:491	arg1	cells					493:497	electroactive cells	479:497	electroactive cells	479:497	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	6	40	theme	poised	1389:1394	arg1	electrodes					1396:1405	poised electrodes	1389:1405	poised electrodes	1389:1405	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	0	41	from	composition	68:78	arg1	insights					50:57	Geobacter biofilms: New insights	26:57	Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances	26:138	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	3	42	theme	special	594:600	arg1	emphasis					602:609	a special emphasis	592:609	a special emphasis on the mechanistic role of EPS	592:640	In this study, the response of Geobacter biofilms to anode potentials was investigated with a special emphasis on the mechanistic role of EPS.
31102858	3	43	from	emphasis	602:609	arg1	role					630:633	the mechanistic role	614:633	the mechanistic role of EPS	614:640	In this study, the response of Geobacter biofilms to anode potentials was investigated with a special emphasis on the mechanistic role of EPS.
31102858	5	44	theme	biofilm	843:849	arg1	region					851:856	especially the biofilm region	828:856	especially the biofilm region closer to electrode surface	828:884	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	0	45	theme	biofilms	36:43	arg1	insights					50:57	Geobacter biofilms: New insights	26:57	Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances	26:138	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	8	46	theme	biofilms	1653:1660	arg1	coping					1662:1667	the Geobacter biofilms coping	1639:1667	the Geobacter biofilms coping with various environments	1639:1693	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
31102858	2	47	theme	polymeric	440:448	arg1	substances					450:459	extracellular polymeric substances	426:459	extracellular polymeric substances (EPS) surrounding electroactive cells	426:497	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	2	47	theme	polymeric	440:448	arg1	EPS					462:464	EPS	462:464	EPS	462:464	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	6	48	theme	Meanwhile	1113:1121	arg1	layers					1199:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	8	49	theme	Geobacter	1643:1651	arg1	coping					1662:1667	the Geobacter biofilms coping	1639:1667	the Geobacter biofilms coping with various environments	1639:1693	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
31102858	3	50	theme	EPS	638:640	arg1	role					630:633	the mechanistic role	614:633	the mechanistic role of EPS	614:640	In this study, the response of Geobacter biofilms to anode potentials was investigated with a special emphasis on the mechanistic role of EPS.
31102858	6	51	theme	interior	1190:1197	arg1	layers					1199:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	5	52	dep	polysaccharides	993:1007	arg1	less					974:977	less	974:977	less	974:977	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	0	53	theme	New	46:48	arg1	insights					50:57	Geobacter biofilms: New insights	26:57	Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances	26:138	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	6	54	theme	increasing	1368:1377	arg1	stress					1379:1384	the increasing stress	1364:1384	the increasing stress by poised electrodes	1364:1405	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	5	55	theme	EPS	1075:1077	arg1	EET					1108:1110	EPS and consequently facilitated EET	1075:1110	EPS and consequently facilitated EET	1075:1110	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	4	56	theme	biofilms	713:720	arg1	activities					663:672	electrochemical activities	647:672	electrochemical activities	647:672	The electrochemical activities and cell viabilities of Geobacter soli biofilms were simultaneously attenuated at 0.4 and 0.6 V compared to -0.2 and 0 V.
31102858	4	56	theme	biofilms	713:720	arg1	viabilities					683:693	cell viabilities	678:693	cell viabilities	678:693	The electrochemical activities and cell viabilities of Geobacter soli biofilms were simultaneously attenuated at 0.4 and 0.6 V compared to -0.2 and 0 V.
31102858	5	57	theme	electron	1033:1040	arg1	capacities					1061:1070	higher electron accepting/donating capacities	1026:1070	higher electron accepting/donating capacities	1026:1070	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	6	58	dep	Meanwhile	1113:1121	arg1	nonconductive					1137:1149	nonconductive	1137:1149	nonconductive	1137:1149	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	3	59	theme	mechanistic	618:628	arg1	role					630:633	the mechanistic role	614:633	the mechanistic role of EPS	614:640	In this study, the response of Geobacter biofilms to anode potentials was investigated with a special emphasis on the mechanistic role of EPS.
31102858	7	60	theme	EPS	1458:1460	arg1	production					1444:1453	the production	1440:1453	the production of EPS under different anode potentials	1440:1493	These results demonstrated that the production of EPS under different anode potentials might be finely regulated by cells to keep balance between EET efficiency and cell-protection.
31102858	8	61	theme	electrochemical	1725:1739	arg1	activity					1741:1748	electrochemical activity	1725:1748	electrochemical activity of anode biofilms	1725:1766	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
31102858	3	62	theme	Geobacter	531:539	arg1	biofilms					541:548	Geobacter biofilms	531:548	Geobacter biofilms	531:548	In this study, the response of Geobacter biofilms to anode potentials was investigated with a special emphasis on the mechanistic role of EPS.
31102858	0	63	from	structure	92:100	arg1	insights					50:57	Geobacter biofilms: New insights	26:57	Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances	26:138	Anode potentials regulate Geobacter biofilms: New insights from the composition and spatial structure of extracellular polymeric substances.
31102858	3	64	theme	biofilms	541:548	arg1	response					519:526	the response	515:526	the response of Geobacter biofilms to anode potentials	515:568	In this study, the response of Geobacter biofilms to anode potentials was investigated with a special emphasis on the mechanistic role of EPS.
31102858	1	65	from	efficiency	183:192	arg1	systems					216:222	bioelectrochemical systems	197:222	bioelectrochemical systems	197:222	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	5	66	theme	more	929:932	arg1	proteins					961:968	relatively more extracellular redox-active proteins	918:968	relatively more extracellular redox-active proteins	918:968	It was found that the biofilms (especially the biofilm region closer to electrode surface) grown at -0.2 and 0 V produced relatively more extracellular redox-active proteins and less extracellular polysaccharides, which conferred higher electron accepting/donating capacities to EPS and consequently facilitated EET.
31102858	8	67	theme	anode	1753:1757	arg1	biofilms					1759:1766	anode biofilms	1753:1766	anode biofilms	1753:1766	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
31102858	6	68	from	cells	1335:1339	arg1	biofilms					1350:1357	these biofilms	1344:1357	these biofilms	1344:1357	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	6	69	theme	polysaccharide-dominated	1165:1188	arg1	layers					1199:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers	1113:1204	Meanwhile, electrically nonconductive extracellular polysaccharide-dominated interior layers were formed in the biofilms grown at 0.4 and 0.6 V, which limited direct EET but might serve as physical barriers for protecting cells in these biofilms from the increasing stress by poised electrodes.
31102858	4	70	dep	activities	663:672	arg1	The					643:645	The	643:645	The	643:645	The electrochemical activities and cell viabilities of Geobacter soli biofilms were simultaneously attenuated at 0.4 and 0.6 V compared to -0.2 and 0 V.
31102858	2	71	theme	bacterial	370:378	arg1	biomass					380:386	bacterial biomass	370:386	bacterial biomass	370:386	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	7	72	theme	EET	1554:1556	arg1	efficiency					1558:1567	EET efficiency	1554:1567	EET efficiency	1554:1567	These results demonstrated that the production of EPS under different anode potentials might be finely regulated by cells to keep balance between EET efficiency and cell-protection.
31102858	2	73	theme	extracellular	426:438	arg1	substances					450:459	extracellular polymeric substances	426:459	extracellular polymeric substances (EPS) surrounding electroactive cells	426:497	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	2	73	theme	extracellular	426:438	arg1	EPS					462:464	EPS	462:464	EPS	462:464	To explore the underlying mechanism, previous studies have mainly focused on EET conduit and bacterial biomass but rarely concerned with the role of extracellular polymeric substances (EPS) surrounding electroactive cells.
31102858	1	74	theme	electron	159:166	arg1	efficiency					183:192	The extracellular electron transfer (EET) efficiency	141:192	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems	141:222	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	1	74	theme	electron	159:166	arg1	dependent					246:254	dependent	246:254	dependent	246:254	The extracellular electron transfer (EET) efficiency in bioelectrochemical systems has been proven to be dependent on anode potentials.
31102858	8	75	with	coping	1662:1667	arg1	environments					1682:1693	various environments	1674:1693	various environments	1674:1693	This study provides a new insight to investigate the Geobacter biofilms coping with various environments, and is useful for optimizing electrochemical activity of anode biofilms.
30802026	4	0	theme	scanning	584:591	arg1	microscopy					602:611	scanning electron microscopy	584:611	scanning electron microscopy	584:611	The morphology of the fertilizer was evaluated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy.
30802026	5	1	theme	elemental	759:767	arg1	analysis					769:776	elemental analysis	759:776	elemental analysis	759:776	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	9	2	theme	environment-friendly	1322:1341	arg1	fertilizer					1343:1352	The pH-responsive environment-friendly fertilizer	1304:1352	The pH-responsive environment-friendly fertilizer	1304:1352	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	5	3	theme	absorption	827:836	arg1	spectroscopy					838:849	UV-vis absorption spectroscopy	820:849	UV-vis absorption spectroscopy	820:849	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	5	4	theme	self-assembly	697:709	arg1	process					711:717	self-assembly process	697:717	self-assembly process	697:717	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	1	5	theme	significant	191:201	arg1	attention					203:211	significant attention	191:211	significant attention	191:211	Layer-by-layer (LBL) self-assembly based on natural polysaccharides is drawing significant attention in various applications.
30802026	5	6	theme	UV-vis	820:825	arg1	spectroscopy					838:849	UV-vis absorption spectroscopy	820:849	UV-vis absorption spectroscopy	820:849	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	3	7	theme	natural	414:420	arg1	layers					438:443	natural polyelectrolyte layers	414:443	natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate	414:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	7	8	theme	room	1094:1097	arg1	temperature					1099:1109	room temperature	1094:1109	room temperature	1094:1109	In an alkaline medium at room temperature, the nutrient release rate can be clearly accelerated compared with that in acidic and neutral media.
30802026	7	9	theme	nutrient	1116:1123	arg1	rate					1133:1136	the nutrient release rate	1112:1136	the nutrient release rate	1112:1136	In an alkaline medium at room temperature, the nutrient release rate can be clearly accelerated compared with that in acidic and neutral media.
30802026	3	10	theme	polyelectrolyte	422:436	arg1	layers					438:443	natural polyelectrolyte layers	414:443	natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate	414:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	6	11	theme	release	1052:1058	arg1	results					1060:1066	the nutrient release results	1039:1066	the nutrient release results	1039:1066	Excellent pH-responsive behavior was observed by the nutrient release results.
30802026	4	12	theme	fertilizer	556:565	arg1	morphology					538:547	The morphology	534:547	The morphology of the fertilizer	534:565	The morphology of the fertilizer was evaluated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy.
30802026	5	13	theme	fertilizer	726:735	arg1	composition					681:691	composition	681:691	composition	681:691	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	5	13	theme	fertilizer	726:735	arg1	process					711:717	self-assembly process	697:717	self-assembly process	697:717	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	8	14	theme	pot	1223:1225	arg1	experiments					1227:1237	pot experiments	1223:1237	pot experiments	1223:1237	Moreover, pot experiments showed that the fertilizer can effectively promote plant growth.
30802026	2	15	from	application	251:261	arg1	fertilizers					266:276	fertilizers	266:276	fertilizers	266:276	However, its application in fertilizers is limited.
30802026	5	16	theme	photoelectron	901:913	arg1	spectroscopy					915:926	X-ray photoelectron spectroscopy	895:926	X-ray photoelectron spectroscopy	895:926	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	6	17	theme	pH-responsive	1000:1012	arg1	behavior					1014:1021	Excellent pH-responsive behavior	990:1021	Excellent pH-responsive behavior	990:1021	Excellent pH-responsive behavior was observed by the nutrient release results.
30802026	5	18	dep	Fourier	779:785	arg1	transform					787:795	transform	787:795	transform infrared spectroscopy	787:817	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	0	19	theme	Environment-Friendly	3:22	arg1	Fertilizer					24:33	An Environment-Friendly Fertilizer	0:33	An Environment-Friendly Fertilizer	0:33	An Environment-Friendly Fertilizer Prepared by Layer-by-Layer Self-Assembly for pH-Responsive Nutrient Release.
30802026	5	20	theme	X-ray	895:899	arg1	spectroscopy					915:926	X-ray photoelectron spectroscopy	895:926	X-ray photoelectron spectroscopy	895:926	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	5	21	theme	thermal	877:883	arg1	analysis					885:892	thermal analysis	877:892	thermal analysis	877:892	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	6	22	theme	nutrient	1043:1050	arg1	results					1060:1066	the nutrient release results	1039:1066	the nutrient release results	1039:1066	Excellent pH-responsive behavior was observed by the nutrient release results.
30802026	3	23	theme	ammonium	509:516	arg1	phosphate					523:531	polydopamine-coated ammonium zinc phosphate	489:531	polydopamine-coated ammonium zinc phosphate	489:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	5	24	theme	coupled	945:951	arg1	spectroscopy					976:987	inductively coupled plasma atomic emission spectroscopy	933:987	inductively coupled plasma atomic emission spectroscopy	933:987	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	4	25	theme	atomic	652:657	arg1	microscopy					665:674	atomic force microscopy	652:674	atomic force microscopy	652:674	The morphology of the fertilizer was evaluated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy.
30802026	7	26	theme	alkaline	1075:1082	arg1	medium					1084:1089	an alkaline medium	1072:1089	an alkaline medium at room temperature	1072:1109	In an alkaline medium at room temperature, the nutrient release rate can be clearly accelerated compared with that in acidic and neutral media.
30802026	5	27	theme	zeta	852:855	arg1	analysis					867:874	zeta potential analysis	852:874	zeta potential analysis	852:874	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	3	28	theme	zinc	518:521	arg1	phosphate					523:531	polydopamine-coated ammonium zinc phosphate	489:531	polydopamine-coated ammonium zinc phosphate	489:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	5	29	theme	plasma	953:958	arg1	spectroscopy					976:987	inductively coupled plasma atomic emission spectroscopy	933:987	inductively coupled plasma atomic emission spectroscopy	933:987	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	3	30	theme	LBL	305:307	arg1	technology					337:346	LBL electrostatic self-assembly technology	305:346	LBL electrostatic self-assembly technology	305:346	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	9	31	theme	nutrient	1366:1373	arg1	release					1375:1381	nutrient release	1366:1381	nutrient release	1366:1381	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	5	32	theme	emission	967:974	arg1	spectroscopy					976:987	inductively coupled plasma atomic emission spectroscopy	933:987	inductively coupled plasma atomic emission spectroscopy	933:987	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	1	33	theme	various	216:222	arg1	applications					224:235	various applications	216:235	various applications	216:235	Layer-by-layer (LBL) self-assembly based on natural polysaccharides is drawing significant attention in various applications.
30802026	3	34	theme	electrostatic	309:321	arg1	technology					337:346	LBL electrostatic self-assembly technology	305:346	LBL electrostatic self-assembly technology	305:346	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	9	35	theme	modern	1459:1464	arg1	green					1466:1470	modern green and sustainable agriculture	1459:1498	green	1466:1470	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	0	36	theme	Layer-by-Layer	47:60	arg1	Self-Assembly					62:74	Layer-by-Layer Self-Assembly	47:74	Layer-by-Layer Self-Assembly	47:74	An Environment-Friendly Fertilizer Prepared by Layer-by-Layer Self-Assembly for pH-Responsive Nutrient Release.
30802026	4	37	theme	force	659:663	arg1	microscopy					665:674	atomic force microscopy	652:674	atomic force microscopy	652:674	The morphology of the fertilizer was evaluated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy.
30802026	7	38	theme	neutral	1198:1204	arg1	media					1206:1210	acidic and neutral media	1187:1210	acidic and neutral media	1187:1210	In an alkaline medium at room temperature, the nutrient release rate can be clearly accelerated compared with that in acidic and neutral media.
30802026	3	39	with	fertilizer	398:407	arg1	layers					438:443	natural polyelectrolyte layers	414:443	natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate	414:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	3	40	theme	polydopamine-coated	489:507	arg1	phosphate					523:531	polydopamine-coated ammonium zinc phosphate	489:531	polydopamine-coated ammonium zinc phosphate	489:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	4	41	theme	electron	627:634	arg1	microscopy					636:645	transmission electron microscopy	614:645	transmission electron microscopy	614:645	The morphology of the fertilizer was evaluated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy.
30802026	8	42	theme	plant	1290:1294	arg1	growth					1296:1301	plant growth	1290:1301	plant growth	1290:1301	Moreover, pot experiments showed that the fertilizer can effectively promote plant growth.
30802026	3	43	theme	lignosulfonate	461:474	arg1	layers					438:443	natural polyelectrolyte layers	414:443	natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate	414:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	4	44	theme	transmission	614:625	arg1	microscopy					636:645	transmission electron microscopy	614:645	transmission electron microscopy	614:645	The morphology of the fertilizer was evaluated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy.
30802026	7	45	theme	acidic	1187:1192	arg1	media					1206:1210	acidic and neutral media	1187:1210	acidic and neutral media	1187:1210	In an alkaline medium at room temperature, the nutrient release rate can be clearly accelerated compared with that in acidic and neutral media.
30802026	3	46	theme	environment-responsive	375:396	arg1	fertilizer					398:407	an environment-responsive fertilizer	372:407	an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate	372:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	9	47	theme	sustainable	1476:1486	arg1	agriculture					1488:1498	modern green and sustainable agriculture	1459:1498	agriculture	1488:1498	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	5	48	theme	infrared	797:804	arg1	spectroscopy					806:817	infrared spectroscopy	797:817	infrared spectroscopy	797:817	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	6	49	theme	Excellent	990:998	arg1	behavior					1014:1021	Excellent pH-responsive behavior	990:1021	Excellent pH-responsive behavior	990:1021	Excellent pH-responsive behavior was observed by the nutrient release results.
30802026	9	50	theme	nutrients	1414:1422	arg1	release					1403:1409	excessive release	1393:1409	excessive release of nutrients	1393:1422	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	9	51	theme	excessive	1393:1401	arg1	release					1403:1409	excessive release	1393:1409	excessive release of nutrients	1393:1422	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	3	52	theme	self-assembly	323:335	arg1	technology					337:346	LBL electrostatic self-assembly technology	305:346	LBL electrostatic self-assembly technology	305:346	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	9	53	theme	promising	1433:1441	arg1	applications					1443:1454	promising applications	1433:1454	promising applications in modern green and sustainable agriculture and horticulture	1433:1515	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	9	54	theme	pH-responsive	1308:1320	arg1	fertilizer					1343:1352	The pH-responsive environment-friendly fertilizer	1304:1352	The pH-responsive environment-friendly fertilizer	1304:1352	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	1	55	theme	natural	156:162	arg1	polysaccharides					164:178	natural polysaccharides	156:178	natural polysaccharides	156:178	Layer-by-layer (LBL) self-assembly based on natural polysaccharides is drawing significant attention in various applications.
30802026	9	56	from	applications	1443:1454	arg1	horticulture					1504:1515	horticulture	1504:1515	horticulture	1504:1515	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	9	56	from	applications	1443:1454	arg1	green					1466:1470	modern green and sustainable agriculture	1459:1498	green	1466:1470	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	9	56	from	applications	1443:1454	arg1	agriculture					1488:1498	modern green and sustainable agriculture	1459:1498	agriculture	1488:1498	The pH-responsive environment-friendly fertilizer can control nutrient release and avoid excessive release of nutrients, showing promising applications in modern green and sustainable agriculture and horticulture.
30802026	0	57	theme	Nutrient	94:101	arg1	Release					103:109	pH-Responsive Nutrient Release	80:109	pH-Responsive Nutrient Release	80:109	An Environment-Friendly Fertilizer Prepared by Layer-by-Layer Self-Assembly for pH-Responsive Nutrient Release.
30802026	7	58	from	temperature	1099:1109	arg1	medium					1084:1089	an alkaline medium	1072:1089	an alkaline medium at room temperature	1072:1109	In an alkaline medium at room temperature, the nutrient release rate can be clearly accelerated compared with that in acidic and neutral media.
30802026	0	59	theme	pH-Responsive	80:92	arg1	Release					103:109	pH-Responsive Nutrient Release	80:109	pH-Responsive Nutrient Release	80:109	An Environment-Friendly Fertilizer Prepared by Layer-by-Layer Self-Assembly for pH-Responsive Nutrient Release.
30802026	4	60	theme	electron	593:600	arg1	microscopy					602:611	scanning electron microscopy	584:611	scanning electron microscopy	584:611	The morphology of the fertilizer was evaluated by scanning electron microscopy, transmission electron microscopy, and atomic force microscopy.
30802026	5	61	theme	atomic	960:965	arg1	spectroscopy					976:987	inductively coupled plasma atomic emission spectroscopy	933:987	inductively coupled plasma atomic emission spectroscopy	933:987	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	7	62	theme	release	1125:1131	arg1	rate					1133:1136	the nutrient release rate	1112:1136	the nutrient release rate	1112:1136	In an alkaline medium at room temperature, the nutrient release rate can be clearly accelerated compared with that in acidic and neutral media.
30802026	3	63	theme	chitosan	448:455	arg1	layers					438:443	natural polyelectrolyte layers	414:443	natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate	414:531	In this study, LBL electrostatic self-assembly technology was employed to prepare an environment-responsive fertilizer with natural polyelectrolyte layers of chitosan and lignosulfonate deposited on polydopamine-coated ammonium zinc phosphate.
30802026	5	64	dep	composition	681:691	arg1	The					677:679	The	677:679	The	677:679	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
30802026	5	65	theme	potential	857:865	arg1	analysis					867:874	zeta potential analysis	852:874	zeta potential analysis	852:874	The composition and self-assembly process of the fertilizer were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-vis absorption spectroscopy, zeta potential analysis, thermal analysis, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy.
31600845	7	0	theme	healthy	1086:1092	arg1	controls					1094:1101	healthy controls	1086:1101	healthy controls	1086:1101	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	9	1	theme	communities	1342:1352	arg1	metagenomics					1316:1327	Predicted metagenomics	1306:1327	Predicted metagenomics of microbial communities	1306:1352	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	9	2	theme	glycan	1376:1381	arg1	biosynthesis					1383:1394	glycan biosynthesis	1376:1394	glycan biosynthesis	1376:1394	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	4	3	theme	rDNA	673:676	arg1	products					697:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products were sequenced.
31600845	3	4	theme	Faecal	571:576	arg1	samples					578:584	Faecal samples	571:584	Faecal samples	571:584	Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals.
31600845	9	5	from	genes	1454:1458	arg1	biosynthesis					1383:1394	glycan biosynthesis	1376:1394	glycan biosynthesis	1376:1394	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	9	5	from	genes	1454:1458	arg1	HBVCLD					1463:1468	HBVCLD	1463:1468	HBVCLD	1463:1468	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	0	6	theme	liver	118:122	arg1	cirrhosis					124:132	liver cirrhosis	118:132	liver cirrhosis	118:132	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	1	7	theme	B	214:214	arg1	HBV					223:225	HBV	223:225	HBV	223:225	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	1	7	theme	B	214:214	arg1	virus					216:220	hepatitis B virus	204:220	hepatitis B virus (HBV) infection	204:236	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	2	8	theme	disease	529:535	arg1	patients					537:544	virus-induced chronic liver disease patients	501:544	virus-induced chronic liver disease patients	501:544	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	7	9	theme	hepatocellular	1032:1045	arg1	HCC					1058:1060	HCC	1058:1060	HCC	1058:1060	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	7	9	theme	hepatocellular	1032:1045	arg1	carcinoma					1047:1055	hepatocellular carcinoma	1032:1055	hepatocellular carcinoma (HCC)	1032:1061	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	9	10	theme	lipid	1429:1433	arg1	genes					1454:1458	lipid metabolism-related genes	1429:1458	lipid metabolism-related genes	1429:1458	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	11	11	theme	CHB	1697:1699	arg1	study					1688:1692	Further study	1680:1692	Further study of CHB, LC and HCC based on microbiota	1680:1731	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	3	12	theme	HBVCLD	624:629	arg1	patients					631:638	HBVCLD patients	624:638	HBVCLD patients	624:638	Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals.
31600845	1	13	from	effect	194:199	arg1	microbiota					245:254	gut microbiota	241:254	gut microbiota	241:254	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	4	14	theme	amplification	683:695	arg1	products					697:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products were sequenced.
31600845	0	15	theme	virus-induced	54:66	arg1	disease					82:88	hepatitis B virus-induced chronic liver disease	42:88	hepatitis B virus-induced chronic liver disease	42:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	1	16	theme	virus-induced	326:338	arg1	HBVCLD					363:368	HBVCLD	363:368	HBVCLD	363:368	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	1	16	theme	virus-induced	326:338	arg1	disease					354:360	virus-induced chronic liver disease	326:360	virus-induced chronic liver disease (HBVCLD)	326:369	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	2	17	theme	different	469:477	arg1	stages					479:484	the three different stages	459:484	the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals	459:568	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	0	18	from	dysbiosis	15:23	arg1	patients					28:35	patients	28:35	patients with hepatitis B virus-induced chronic liver disease	28:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	11	19	theme	HCC	1709:1711	arg1	study					1688:1692	Further study	1680:1692	Further study of CHB, LC and HCC based on microbiota	1680:1731	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	0	20	theme	liver	76:80	arg1	disease					82:88	hepatitis B virus-induced chronic liver disease	42:88	hepatitis B virus-induced chronic liver disease	42:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	1	21	theme	liver	348:352	arg1	HBVCLD					363:368	HBVCLD	363:368	HBVCLD	363:368	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	1	21	theme	liver	348:352	arg1	disease					354:360	virus-induced chronic liver disease	326:360	virus-induced chronic liver disease (HBVCLD)	326:369	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	7	22	theme	HBVCLD	957:962	arg1	patients					964:971	HBVCLD patients	957:971	HBVCLD patients	957:971	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	2	23	theme	chronic	515:521	arg1	disease					529:535	virus-induced chronic liver disease	501:535	virus-induced chronic liver disease patients	501:544	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	11	24	theme	LC	1702:1703	arg1	study					1688:1692	Further study	1680:1692	Further study of CHB, LC and HCC based on microbiota	1680:1731	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	5	25	theme	alpha	755:759	arg1	diversity					761:769	alpha diversity	755:769	alpha diversity	755:769	Bioinformatic analysis including alpha diversity and PICRUSt was performed.
31600845	7	26	theme	controls	944:951	arg1	clustering					922:931	a separate clustering	911:931	a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC)	911:1061	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	2	27	theme	B	499:499	arg1	stages					479:484	the three different stages	459:484	the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals	459:568	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	10	28	theme	potential	1607:1615	arg1	bacteria					1617:1624	potential bacteria	1607:1624	potential bacteria	1607:1624	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	2	29	theme	gut	429:431	arg1	composition					444:454	the gut microbiota composition	425:454	the gut microbiota composition	425:454	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	8	30	theme	healthy	1288:1294	arg1	controls					1296:1303	healthy controls	1288:1303	healthy controls	1288:1303	The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls.
31600845	11	31	theme	novel	1806:1810	arg1	strategy					1822:1829	a novel treatment strategy	1804:1829	HBVCLD as well as a novel treatment strategy	1786:1829	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	0	32	theme	Gut	0:2	arg1	dysbiosis					15:23	Gut microbiota dysbiosis	0:23	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease	0:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	7	33	theme	separate	913:920	arg1	clustering					922:931	a separate clustering	911:931	a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC)	911:1061	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	1	34	theme	gut	285:287	arg1	dysbiosis					300:308	gut microbiota dysbiosis	285:308	gut microbiota dysbiosis	285:308	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	9	35	from	increase	1364:1371	arg1	biosynthesis					1383:1394	glycan biosynthesis	1376:1394	glycan biosynthesis	1376:1394	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	9	35	from	increase	1364:1371	arg1	HBVCLD					1463:1468	HBVCLD	1463:1468	HBVCLD	1463:1468	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	6	36	theme	225	859:861	arg1	genera					863:868	225 genera	859:868	225 genera	859:868	A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera were detected.
31600845	6	36	theme	225	859:861	arg1	phyla					812:816	19 phyla	809:816	19 phyla	809:816	A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera were detected.
31600845	10	37	from	gain	1599:1602	arg1	genes					1673:1677	genes	1673:1677	genes	1673:1677	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	10	37	from	gain	1599:1602	arg1	bacteria					1661:1668	potential beneficial bacteria	1640:1668	potential beneficial bacteria	1640:1668	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	10	37	from	gain	1599:1602	arg1	bacteria					1617:1624	potential bacteria	1607:1624	potential bacteria	1607:1624	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	0	38	theme	hepatitis	42:50	arg1	B					52:52	hepatitis B	42:52	hepatitis B virus-induced chronic liver disease	42:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	1	39	theme	hepatitis	314:322	arg1	B					324:324	hepatitis B	314:324	hepatitis B	314:324	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	11	40	theme	Further	1680:1686	arg1	study					1688:1692	Further study	1680:1692	Further study of CHB, LC and HCC based on microbiota	1680:1731	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	10	41	theme	potential	1640:1648	arg1	bacteria					1661:1668	potential beneficial bacteria	1640:1668	potential beneficial bacteria	1640:1668	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	9	42	theme	Predicted	1306:1314	arg1	metagenomics					1316:1327	Predicted metagenomics	1306:1327	Predicted metagenomics of microbial communities	1306:1352	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	8	43	with	patients	1250:1257	arg1	HCC					1276:1278	HCC	1276:1278	HCC	1276:1278	The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls.
31600845	8	43	with	patients	1250:1257	arg1	LC					1269:1270	LC	1269:1270	LC	1269:1270	The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls.
31600845	8	43	with	patients	1250:1257	arg1	CHB					1264:1266	CHB	1264:1266	CHB	1264:1266	The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls.
31600845	1	44	theme	infection	228:236	arg1	effect					194:199	the effect	190:199	the effect of hepatitis B virus (HBV) infection on gut microbiota	190:254	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	0	45	theme	B	52:52	arg1	disease					82:88	hepatitis B virus-induced chronic liver disease	42:88	hepatitis B virus-induced chronic liver disease	42:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	10	46	from	loss	1632:1635	arg1	genes					1673:1677	genes	1673:1677	genes	1673:1677	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	10	46	from	loss	1632:1635	arg1	bacteria					1661:1668	potential beneficial bacteria	1640:1668	potential beneficial bacteria	1640:1668	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	10	46	from	loss	1632:1635	arg1	bacteria					1617:1624	potential bacteria	1607:1624	potential bacteria	1607:1624	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	0	47	with	patients	28:35	arg1	disease					82:88	hepatitis B virus-induced chronic liver disease	42:88	hepatitis B virus-induced chronic liver disease	42:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	1	48	theme	gut	241:243	arg1	microbiota					245:254	gut microbiota	241:254	gut microbiota	241:254	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	7	49	theme	gut	1068:1070	arg1	microbiota					1072:1081	gut microbiota	1068:1081	gut microbiota of healthy controls	1068:1101	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	6	50	theme	phyla	812:816	arg1	total					800:804	A total	798:804	A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera	798:868	A total of 19 phyla, 43 classes, 72 orders, 126 families and 225 genera were detected.
31600845	8	51	theme	Firmicutes	1196:1205	arg1	lower					1211:1215	lower	1211:1215	lower	1211:1215	The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls.
31600845	8	51	theme	Firmicutes	1196:1205	arg1	abundance					1183:1191	The abundance	1179:1191	The abundance of Firmicutes	1179:1205	The abundance of Firmicutes was lower, and Bacteroidetes was higher in patients with CHB, LC and HCC than in healthy controls.
31600845	4	52	theme	16S	669:671	arg1	products					697:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products were sequenced.
31600845	10	53	theme	gut	1550:1552	arg1	dysbiosis					1554:1562	gut dysbiosis	1550:1562	gut dysbiosis	1550:1562	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	1	54	theme	hepatitis	204:212	arg1	HBV					223:225	HBV	223:225	HBV	223:225	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	1	54	theme	hepatitis	204:212	arg1	virus					216:220	hepatitis B virus	204:220	hepatitis B virus (HBV) infection	204:236	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	11	55	theme	HBVCLD	1786:1791	arg1	pathogenesis					1770:1781	the pathogenesis	1766:1781	the pathogenesis of HBVCLD as well as a novel treatment strategy	1766:1829	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	5	56	theme	Bioinformatic	722:734	arg1	analysis					736:743	Bioinformatic analysis	722:743	Bioinformatic analysis including alpha diversity and PICRUSt	722:781	Bioinformatic analysis including alpha diversity and PICRUSt was performed.
31600845	3	57	theme	clinical	590:597	arg1	data					599:602	clinical data	590:602	clinical data	590:602	Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals.
31600845	1	58	theme	virus	216:220	arg1	infection					228:236	hepatitis B virus (HBV) infection	204:236	hepatitis B virus (HBV) infection	204:236	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	2	59	theme	liver	523:527	arg1	disease					529:535	virus-induced chronic liver disease	501:535	virus-induced chronic liver disease patients	501:544	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	7	60	theme	liver	1007:1011	arg1	LC					1024:1025	LC	1024:1025	LC	1024:1025	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	7	60	theme	liver	1007:1011	arg1	cirrhosis					1013:1021	liver cirrhosis	1007:1021	liver cirrhosis (LC)	1007:1026	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	9	61	theme	metabolism-related	1435:1452	arg1	genes					1454:1458	lipid metabolism-related genes	1429:1458	lipid metabolism-related genes	1429:1458	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	11	62	theme	novel	1747:1751	arg1	insight					1753:1759	a novel insight	1745:1759	a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy	1745:1829	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	2	63	theme	healthy	550:556	arg1	individuals					558:568	healthy individuals	550:568	healthy individuals	550:568	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	0	64	theme	chronic	68:74	arg1	disease					82:88	hepatitis B virus-induced chronic liver disease	42:88	hepatitis B virus-induced chronic liver disease	42:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	9	65	theme	metabolism-related	1400:1417	arg1	genes					1419:1423	metabolism-related genes	1400:1423	metabolism-related genes	1400:1423	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	4	66	theme	gene	678:681	arg1	products					697:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products	665:704	The 16S rDNA gene amplification products were sequenced.
31600845	1	67	theme	chronic	340:346	arg1	HBVCLD					363:368	HBVCLD	363:368	HBVCLD	363:368	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	1	67	theme	chronic	340:346	arg1	disease					354:360	virus-induced chronic liver disease	326:360	virus-induced chronic liver disease (HBVCLD)	326:369	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	7	68	theme	chronic	982:988	arg1	hepatitis					990:998	chronic hepatitis	982:998	chronic hepatitis (CHB)	982:1004	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	7	68	theme	chronic	982:988	arg1	CHB					1001:1003	CHB	1001:1003	CHB	1001:1003	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	9	69	theme	healthy	1478:1484	arg1	individuals					1486:1496	healthy individuals	1478:1496	healthy individuals	1478:1496	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	0	70	theme	chronic	99:105	arg1	hepatitis					107:115	chronic hepatitis	99:115	chronic hepatitis	99:115	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	7	71	theme	patients	964:971	arg1	clustering					922:931	a separate clustering	911:931	a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC)	911:1061	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	2	72	theme	virus-induced	501:513	arg1	disease					529:535	virus-induced chronic liver disease	501:535	virus-induced chronic liver disease patients	501:544	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	2	73	theme	hepatitis	489:497	arg1	B					499:499	hepatitis B virus-induced chronic liver disease patients and healthy individuals	489:568	hepatitis B virus-induced chronic liver disease patients and healthy individuals	489:568	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	1	74	dep	dysbiosis	300:308	arg1	HBVCLD					363:368	HBVCLD	363:368	HBVCLD	363:368	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	1	74	dep	dysbiosis	300:308	arg1	disease					354:360	virus-induced chronic liver disease	326:360	virus-induced chronic liver disease (HBVCLD)	326:369	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	0	75	theme	microbiota	4:13	arg1	dysbiosis					15:23	Gut microbiota dysbiosis	0:23	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease	0:88	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	7	76	theme	healthy	936:942	arg1	controls					944:951	healthy controls	936:951	healthy controls	936:951	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	0	77	theme	hepatocellular	138:151	arg1	carcinoma					153:161	hepatocellular carcinoma	138:161	hepatocellular carcinoma	138:161	Gut microbiota dysbiosis in patients with hepatitis B virus-induced chronic liver disease covering chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
31600845	11	78	theme	treatment	1812:1820	arg1	strategy					1822:1829	a novel treatment strategy	1804:1829	HBVCLD as well as a novel treatment strategy	1786:1829	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	2	79	dep	B	499:499	arg1	patients					537:544	virus-induced chronic liver disease patients	501:544	virus-induced chronic liver disease patients	501:544	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	2	79	dep	B	499:499	arg1	individuals					558:568	healthy individuals	550:568	healthy individuals	550:568	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	3	80	theme	healthy	644:650	arg1	individuals					652:662	healthy individuals	644:662	healthy individuals	644:662	Faecal samples and clinical data were collected from HBVCLD patients and healthy individuals.
31600845	1	81	theme	microbiota	289:298	arg1	dysbiosis					300:308	gut microbiota dysbiosis	285:308	gut microbiota dysbiosis	285:308	The information regarding the effect of hepatitis B virus (HBV) infection on gut microbiota and the relationship between gut microbiota dysbiosis and hepatitis B virus-induced chronic liver disease (HBVCLD) is limited.
31600845	11	82	theme	strategy	1822:1829	arg1	pathogenesis					1770:1781	the pathogenesis	1766:1781	the pathogenesis of HBVCLD as well as a novel treatment strategy	1766:1829	Further study of CHB, LC and HCC based on microbiota may provide a novel insight into the pathogenesis of HBVCLD as well as a novel treatment strategy.
31600845	7	83	theme	controls	1094:1101	arg1	microbiota					1072:1081	gut microbiota	1068:1081	gut microbiota of healthy controls	1068:1101	The beta-diversity showed a separate clustering of healthy controls and HBVCLD patients covering chronic hepatitis (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC); and gut microbiota of healthy controls was more consistent, whereas those of CHB, LC and HCC varied substantially.
31600845	2	84	theme	microbiota	433:442	arg1	composition					444:454	the gut microbiota composition	425:454	the gut microbiota composition	425:454	In this study, we aimed at characterizing the gut microbiota composition in the three different stages of hepatitis B virus-induced chronic liver disease patients and healthy individuals.
31600845	10	85	theme	beneficial	1650:1659	arg1	bacteria					1661:1668	potential beneficial bacteria	1640:1668	potential beneficial bacteria	1640:1668	Our study suggested that HBVCLD is associated with gut dysbiosis, with characteristics including, a gain in potential bacteria and a loss in potential beneficial bacteria or genes.
31600845	9	86	from	genes	1419:1423	arg1	biosynthesis					1383:1394	glycan biosynthesis	1376:1394	glycan biosynthesis	1376:1394	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	9	86	from	genes	1419:1423	arg1	HBVCLD					1463:1468	HBVCLD	1463:1468	HBVCLD	1463:1468	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31600845	9	87	theme	microbial	1332:1340	arg1	communities					1342:1352	microbial communities	1332:1352	microbial communities	1332:1352	Predicted metagenomics of microbial communities showed an increase in glycan biosynthesis and metabolism-related genes and lipid metabolism-related genes in HBVCLD than in healthy individuals.
31544308	8	0	theme	DNA/RNA	1200:1206	arg1	B					1166:1166	vitamin B	1158:1166	vitamin B	1158:1166	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	8	0	theme	DNA/RNA	1200:1206	arg1	synthesis					1208:1216	DNA/RNA synthesis	1200:1216	DNA/RNA synthesis	1200:1216	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	4	1	theme	decompensated	578:590	arg1	compensated/43					563:576	46 controls/50 compensated/43 decompensated	548:590	46 controls/50 compensated/43 decompensated	548:590	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	4	1	theme	decompensated	578:590	arg1	Turkish					539:545	139 Turkish	535:545	139 Turkish (46 controls/50 compensated/43 decompensated)	535:591	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	7	2	theme	Correlation	916:926	arg1	differences					936:946	Correlation network differences	916:946	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA	916:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	6	3	theme	gut	822:824	arg1	functionalities					836:850	Predicted gut microbial functionalities	812:850	Predicted gut microbial functionalities	812:850	Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries.
31544308	2	4	theme	90-day	344:349	arg1	hospitalizations					351:366	90-day hospitalizations	344:366	90-day hospitalizations	344:366	Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations.
31544308	8	5	theme	lower	1080:1084	arg1	acid					1092:1095	lower amino acid	1080:1095	lower amino acid	1080:1095	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	4	6	theme	controls/59	623:633	arg1	compensated/50					635:648	48 controls/59 compensated/50 decompensated	620:662	48 controls/59 compensated/50 decompensated	620:662	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	4	6	theme	controls/59	623:633	arg1	subjects					610:617	157 American subjects	597:617	157 American subjects (48 controls/59 compensated/50 decompensated)	597:663	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	13	7	theme	altered	1857:1863	arg1	metabolomics					1872:1883	altered plasma metabolomics	1857:1883	altered plasma metabolomics	1857:1883	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	5	8	theme	Mediterranean	716:728	arg1	diet					730:733	a modified Mediterranean diet	705:733	a modified Mediterranean diet with daily fermented milk intake	705:766	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	14	9	theme	diet-microbial	2004:2017	arg1	interactions					2019:2030	These altered diet-microbial interactions	1990:2030	These altered diet-microbial interactions	1990:2030	These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk.
31544308	4	10	theme	decompensated	650:662	arg1	compensated/50					635:648	48 controls/59 compensated/50 decompensated	620:662	48 controls/59 compensated/50 decompensated	620:662	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	4	10	theme	decompensated	650:662	arg1	subjects					610:617	157 American subjects	597:617	157 American subjects (48 controls/59 compensated/50 decompensated)	597:663	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	13	11	theme	modified	1809:1816	arg1	diet					1832:1835	A modified Mediterranean diet	1807:1835	A modified Mediterranean diet	1807:1835	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	9	12	theme	higher	1299:1304	arg1	levels					1323:1328	higher relative lactate levels	1299:1328	higher relative lactate levels	1299:1328	Plasma metabolomics demonstrated higher relative lactate levels in Turkey vs the USA.
31544308	2	13	theme	microbial	234:242	arg1	diversity					244:252	microbial diversity	234:252	microbial diversity	234:252	Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations.
31544308	12	14	theme	linkage	1647:1653	arg1	differences					1655:1665	linkage differences	1647:1665	linkage differences	1647:1665	Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
31544308	0	15	from	impact	65:70	arg1	cirrhosis					98:106	cirrhosis	98:106	cirrhosis	98:106	Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.
31544308	9	16	theme	lactate	1315:1321	arg1	levels					1323:1328	higher relative lactate levels	1299:1328	higher relative lactate levels	1299:1328	Plasma metabolomics demonstrated higher relative lactate levels in Turkey vs the USA.
31544308	2	17	from	Turkish	284:290	arg1	cirrhotics					268:277	cirrhotics	268:277	cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations	268:366	Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations.
31544308	7	18	from	Turkey	1002:1007	arg1	differences					936:946	Correlation network differences	916:946	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA	916:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	7	18	from	Turkey	1002:1007	arg1	cirrhotics					986:995	cirrhotics	986:995	cirrhotics from Turkey vs the USA	986:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	4	19	from	subjects	610:617	arg1	all					530:532	all	530:532	all	530:532	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	4	20	from	Turkish	539:545	arg1	all					530:532	all	530:532	all	530:532	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	0	21	theme	dietary	75:81	arg1	differences					83:93	dietary differences	75:93	dietary differences in cirrhosis	75:106	Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.
31544308	5	22	dep	consumed	696:703	arg1	whereas					769:775	whereas	769:775	whereas	769:775	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	10	23	theme	reduced	1475:1481	arg1	lipids					1483:1488	reduced lipids	1475:1488	reduced lipids	1475:1488	The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines.
31544308	5	24	theme	fermented	746:754	arg1	intake					761:766	daily fermented milk intake	740:766	daily fermented milk intake	740:766	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	12	25	from	networks	1611:1618	arg1	cirrhotics					1623:1632	cirrhotics	1623:1632	cirrhotics	1623:1632	Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
31544308	12	26	theme	unsaturated	1734:1744	arg1	lipids					1746:1751	unsaturated lipids	1734:1751	unsaturated lipids	1734:1751	Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
31544308	7	27	from	differences	936:946	arg1	Turkey					1002:1007	Turkey	1002:1007	Turkey	1002:1007	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	7	27	from	differences	936:946	arg1	USA					1016:1018	USA	1016:1018	USA	1016:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	7	27	from	differences	936:946	arg1	cirrhotics					986:995	cirrhotics	986:995	cirrhotics from Turkey vs the USA	986:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	8	28	theme	lipid	1116:1120	arg1	pathways					1122:1129	lipid pathways	1116:1129	lipid pathways	1116:1129	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	3	29	theme	metabolomic	417:427	arg1	changes					429:435	gut microbial functional and metabolomic changes	388:435	gut microbial functional and metabolomic changes	388:435	We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets.
31544308	6	30	theme	Predicted	812:820	arg1	functionalities					836:850	Predicted gut microbial functionalities	812:850	Predicted gut microbial functionalities	812:850	Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries.
31544308	0	31	theme	microbial	17:25	arg1	composition					27:37	microbial composition	17:37	microbial composition	17:37	Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.
31544308	1	32	theme	BACKGROUND	109:118	arg1	&					120:120	BACKGROUND &	109:120	BACKGROUND &	109:120	BACKGROUND & AIMS Dietary changes can modulate gut microbiota and interact with cirrhosis.
31544308	3	33	theme	functional	402:411	arg1	changes					429:435	gut microbial functional and metabolomic changes	388:435	gut microbial functional and metabolomic changes	388:435	We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets.
31544308	13	34	theme	Western	1963:1969	arg1	diet					1971:1974	Western diet	1963:1974	Western diet in cirrhosis	1963:1987	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	5	35	theme	Western	798:804	arg1	diet					806:809	a Western diet	796:809	a Western diet	796:809	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	6	36	theme	between/within	890:903	arg1	countries					905:913	between/within countries	890:913	between/within countries	890:913	Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries.
31544308	3	37	theme	gut	388:390	arg1	changes					429:435	gut microbial functional and metabolomic changes	388:435	gut microbial functional and metabolomic changes	388:435	We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets.
31544308	2	38	theme	prior	204:208	arg1	study					210:214	Our prior study	200:214	Our prior study	200:214	Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations.
31544308	10	39	theme	decompensated	1378:1390	arg1	cirrhosis					1392:1400	decompensated cirrhosis	1378:1400	decompensated cirrhosis	1378:1400	The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines.
31544308	6	40	theme	plasma	856:861	arg1	metabolomics					863:874	plasma metabolomics	856:874	plasma metabolomics	856:874	Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries.
31544308	8	41	theme	xenobiotic	1177:1186	arg1	metabolism					1188:1197	xenobiotic metabolism	1177:1197	xenobiotic metabolism	1177:1197	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	8	41	theme	xenobiotic	1177:1186	arg1	B					1166:1166	vitamin B	1158:1166	vitamin B	1158:1166	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	14	42	theme	90-day	2061:2066	arg1	risk					2084:2087	the 90-day hospitalization risk	2057:2087	the 90-day hospitalization risk	2057:2087	These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk.
31544308	4	43	from	METHODS	519:525	arg1	all					530:532	all	530:532	all	530:532	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	3	44	theme	Western	504:510	arg1	diets					512:516	Western diets	504:516	Western diets	504:516	We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets.
31544308	8	45	from	Turkey	1238:1243	arg1	cirrhotics					1222:1231	cirrhotics	1222:1231	cirrhotics from Turkey compared to the USA	1222:1263	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	13	46	theme	plasma	1865:1870	arg1	metabolomics					1872:1883	altered plasma metabolomics	1857:1883	altered plasma metabolomics	1857:1883	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	6	47	theme	microbial	826:834	arg1	functionalities					836:850	Predicted gut microbial functionalities	812:850	Predicted gut microbial functionalities	812:850	Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries.
31544308	7	48	theme	network	928:934	arg1	differences					936:946	Correlation network differences	916:946	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA	916:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	8	49	theme	microbial	1054:1062	arg1	function					1064:1071	microbial function	1054:1071	microbial function	1054:1071	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	10	50	theme	similar	1432:1438	arg1	trends					1440:1445	similar trends	1432:1445	similar trends in Turkey and the USA	1432:1467	The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines.
31544308	13	51	dep	CONCLUSIONS	1795:1805	arg1	associated					1841:1850	associated	1841:1850	associated with altered plasma metabolomics	1841:1883	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	13	51	dep	CONCLUSIONS	1795:1805	arg1	alters					1902:1907	alters	1902:1907	beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis	1889:1987	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	8	52	theme	amino	1086:1090	arg1	acid					1092:1095	lower amino acid	1080:1095	lower amino acid	1080:1095	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	5	53	theme	modified	707:714	arg1	diet					730:733	a modified Mediterranean diet	705:733	a modified Mediterranean diet with daily fermented milk intake	705:766	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	9	54	theme	Plasma	1266:1271	arg1	metabolomics					1273:1284	Plasma metabolomics	1266:1284	Plasma metabolomics	1266:1284	Plasma metabolomics demonstrated higher relative lactate levels in Turkey vs the USA.
31544308	0	55	from	differences	83:93	arg1	cirrhosis					98:106	cirrhosis	98:106	cirrhosis	98:106	Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.
31544308	14	56	theme	altered	1996:2002	arg1	interactions					2019:2030	These altered diet-microbial interactions	1990:2030	These altered diet-microbial interactions	1990:2030	These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk.
31544308	13	57	theme	Mediterranean	1818:1830	arg1	diet					1832:1835	A modified Mediterranean diet	1807:1835	A modified Mediterranean diet	1807:1835	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	5	58	theme	Turkish	679:685	arg1	subjects					687:694	Turkish subjects	679:694	Turkish subjects	679:694	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	9	59	theme	relative	1306:1313	arg1	levels					1323:1328	higher relative lactate levels	1299:1328	higher relative lactate levels	1299:1328	Plasma metabolomics demonstrated higher relative lactate levels in Turkey vs the USA.
31544308	12	60	theme	beneficial	1675:1684	arg1	taxa					1686:1689	beneficial taxa	1675:1689	beneficial taxa	1675:1689	Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
31544308	1	61	theme	Dietary	127:133	arg1	changes					135:141	Dietary changes	127:141	Dietary changes	127:141	BACKGROUND & AIMS Dietary changes can modulate gut microbiota and interact with cirrhosis.
31544308	12	62	theme	American	1776:1783	arg1	patients					1785:1792	American patients	1776:1792	American patients	1776:1792	Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
31544308	0	63	from	cirrhosis	98:106	arg1	impact					65:70	the impact	61:70	the impact of dietary differences in cirrhosis	61:106	Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.
31544308	10	64	from	changes	1367:1373	arg1	cirrhosis					1392:1400	decompensated cirrhosis	1378:1400	decompensated cirrhosis	1378:1400	The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines.
31544308	7	65	from	USA	1016:1018	arg1	differences					936:946	Correlation network differences	916:946	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA	916:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	7	65	from	USA	1016:1018	arg1	cirrhotics					986:995	cirrhotics	986:995	cirrhotics from Turkey vs the USA	986:1018	Correlation network differences between microbiota and metabolites in cirrhotics from Turkey vs the USA were evaluated.
31544308	0	66	theme	differences	83:93	arg1	impact					65:70	the impact	61:70	the impact of dietary differences in cirrhosis	61:106	Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.
31544308	1	67	theme	gut	156:158	arg1	microbiota					160:169	gut microbiota	156:169	gut microbiota	156:169	BACKGROUND & AIMS Dietary changes can modulate gut microbiota and interact with cirrhosis.
31544308	2	68	from	USA	299:301	arg1	cirrhotics					268:277	cirrhotics	268:277	cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations	268:366	Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations.
31544308	5	69	theme	daily	740:744	arg1	intake					761:766	daily fermented milk intake	740:766	daily fermented milk intake	740:766	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	12	70	theme	Correlation	1599:1609	arg1	networks					1611:1618	Correlation networks	1599:1618	Correlation networks in cirrhotics	1599:1632	Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
31544308	5	71	theme	milk	756:759	arg1	intake					761:766	daily fermented milk intake	740:766	daily fermented milk intake	740:766	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	13	72	from	diet	1971:1974	arg1	cirrhosis					1979:1987	cirrhosis	1979:1987	cirrhosis	1979:1987	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	8	73	theme	related	1147:1153	arg1	functions					1137:1145	functions	1137:1145	functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis	1137:1216	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	5	74	with	diet	730:733	arg1	intake					761:766	daily fermented milk intake	740:766	daily fermented milk intake	740:766	Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake, whereas Americans consumed a Western diet.
31544308	4	75	theme	controls/50	551:561	arg1	compensated/43					563:576	46 controls/50 compensated/43 decompensated	548:590	46 controls/50 compensated/43 decompensated	548:590	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	4	75	theme	controls/50	551:561	arg1	Turkish					539:545	139 Turkish	535:545	139 Turkish (46 controls/50 compensated/43 decompensated)	535:591	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	10	76	theme	metabolite	1356:1365	arg1	changes					1367:1373	The metabolite changes	1352:1373	The metabolite changes in decompensated cirrhosis	1352:1400	The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines.
31544308	8	77	theme	vitamin	1158:1164	arg1	synthesis					1208:1216	DNA/RNA synthesis	1200:1216	DNA/RNA synthesis	1200:1216	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	8	77	theme	vitamin	1158:1164	arg1	glycan					1169:1174	glycan	1169:1174	glycan	1169:1174	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	8	77	theme	vitamin	1158:1164	arg1	metabolism					1188:1197	xenobiotic metabolism	1177:1197	xenobiotic metabolism	1177:1197	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	8	77	theme	vitamin	1158:1164	arg1	B					1166:1166	vitamin B	1158:1166	vitamin B	1158:1166	RESULTS Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in cirrhotics from Turkey compared to the USA.
31544308	10	78	from	trends	1440:1445	arg1	Turkey					1450:1455	Turkey	1450:1455	Turkey	1450:1455	The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines.
31544308	10	78	from	trends	1440:1445	arg1	USA					1465:1467	USA	1465:1467	USA	1465:1467	The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and the USA, with reduced lipids and phosphocholines.
31544308	3	79	theme	microbial	392:400	arg1	changes					429:435	gut microbial functional and metabolomic changes	388:435	gut microbial functional and metabolomic changes	388:435	We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets.
31544308	2	80	theme	lower	330:334	arg1	risk					336:339	lower risk	330:339	lower risk of 90-day hospitalizations	330:366	Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations.
31544308	12	81	from	differences	1655:1665	arg1	Turkey					1757:1762	Turkey	1757:1762	Turkey	1757:1762	Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients.
31544308	4	82	theme	American	601:608	arg1	compensated/50					635:648	48 controls/59 compensated/50 decompensated	620:662	48 controls/59 compensated/50 decompensated	620:662	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	4	82	theme	American	601:608	arg1	subjects					610:617	157 American subjects	597:617	157 American subjects (48 controls/59 compensated/50 decompensated)	597:663	METHODS In all, 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied.
31544308	3	83	theme	Mediterranean	478:490	arg1	benefits					462:469	benefits	462:469	benefits of the Mediterranean compared to Western diets	462:516	We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets.
31544308	14	84	theme	hospitalization	2068:2082	arg1	risk					2084:2087	the 90-day hospitalization risk	2057:2087	the 90-day hospitalization risk	2057:2087	These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk.
31544308	13	85	theme	microbiota	1909:1918	arg1	functionality					1920:1932	microbiota functionality	1909:1932	microbiota functionality	1909:1932	CONCLUSIONS A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis.
31544308	2	86	theme	hospitalizations	351:366	arg1	risk					336:339	lower risk	330:339	lower risk of 90-day hospitalizations	330:366	Our prior study demonstrated that microbial diversity was higher in cirrhotics from Turkish vs the USA, which was associated with lower risk of 90-day hospitalizations.
30563903	9	0	theme	important	1577:1585	arg1	formation					1651:1659	intravascular thrombus formation	1628:1659	intravascular thrombus formation	1628:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	0	theme	important	1577:1585	arg1	mechanisms					1609:1618	important antimicrobial defense mechanisms	1577:1618	important antimicrobial defense mechanisms such as intravascular thrombus formation	1577:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	7	1	from	patients	1270:1277	arg1	fXII					1243:1246	mutant fXII	1236:1246	mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII)	1236:1322	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	7	1	from	patients	1270:1277	arg1	fXII-Thr309Lys					1249:1262	fXII-Thr309Lys	1249:1262	fXII-Thr309Lys	1249:1262	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	6	2	gly	glycosylated	1135:1146	arg1	threonine					1148:1156	an O-linked glycosylated threonine	1123:1156	an O-linked glycosylated threonine	1123:1156	At both sites, cleavage occurs between proline and an O-linked glycosylated threonine, and deglycosylation of fXII prevents cleavage by CpaA.
30563903	9	3	theme	blood	2111:2115	arg1	coagulation					2117:2127	blood coagulation	2111:2127	blood coagulation	2111:2127	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	2	4	theme	clotting	414:421	arg1	time					423:426	clotting time	414:426	clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay	414:523	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	9	5	theme	defense	1601:1607	arg1	formation					1651:1659	intravascular thrombus formation	1628:1659	intravascular thrombus formation	1628:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	5	theme	defense	1601:1607	arg1	mechanisms					1609:1618	important antimicrobial defense mechanisms	1577:1618	important antimicrobial defense mechanisms such as intravascular thrombus formation	1577:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	6	theme	membrane	1911:1918	arg1	OmpA					1926:1929	the outer membrane porin OmpA	1901:1929	the outer membrane porin OmpA	1901:1929	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	3	7	contain	has	683:685	arg1	CpaA					545:548	CpaA	545:548	CpaA	545:548	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	3	7	contain	has	683:685	arg2	effect					702:707	no discernible effect	687:707	no discernible effect	687:707	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	6	8	gly	deglycosylation	1163:1177	arg1	fXII					1182:1185	fXII	1182:1185	fXII	1182:1185	At both sites, cleavage occurs between proline and an O-linked glycosylated threonine, and deglycosylation of fXII prevents cleavage by CpaA.
30563903	7	9	with	Consistent	1214:1223	arg1	this					1230:1233	this	1230:1233	this	1230:1233	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	3	10	theme	intrinsic	570:578	arg1	pathway					592:598	the intrinsic coagulation pathway	566:598	the intrinsic coagulation pathway	566:598	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	9	11	theme	intravascular	1628:1640	arg1	formation					1651:1659	intravascular thrombus formation	1628:1659	intravascular thrombus formation	1628:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	12	theme	coagulation	2150:2160	arg1	XII					2169:2171	coagulation factor XII	2150:2171	coagulation factor XII	2150:2171	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	12	theme	coagulation	2150:2160	arg1	target					2178:2183	a target	2176:2183	a target of CpaA	2176:2191	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	1	13	theme	nosocomial	233:242	arg1	infections					283:292	wound infections	277:292	wound infections	277:292	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	13	theme	nosocomial	233:242	arg1	bacteremia					299:308	bacteremia	299:308	bacteremia	299:308	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	13	theme	nosocomial	233:242	arg1	infections					244:253	difficult-to-treat nosocomial infections	214:253	difficult-to-treat nosocomial infections	214:253	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	13	theme	nosocomial	233:242	arg1	pneumonia					266:274	pneumonia	266:274	pneumonia	266:274	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	9	14	dep	inhibits	2102:2109	arg1	show					2222:2225	show	2222:2225	show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	2222:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	14	dep	inhibits	2102:2109	arg1	map					2194:2196	map	2194:2196	map the cleavage sites	2194:2215	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	14	dep	inhibits	2102:2109	arg1	identify					2141:2148	identify	2141:2148	identify coagulation factor XII as a target of CpaA	2141:2191	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	6	15	theme	fXII	1182:1185	arg1	deglycosylation					1163:1177	deglycosylation	1163:1177	deglycosylation of fXII	1163:1185	At both sites, cleavage occurs between proline and an O-linked glycosylated threonine, and deglycosylation of fXII prevents cleavage by CpaA.
30563903	10	16	theme	system	2458:2463	arg1	components					2427:2436	highly glycosylated components	2407:2436	highly glycosylated components of the host defense system	2407:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	2	17	theme	thromboplastin	492:505	arg1	time					507:510	partial thromboplastin time	484:510	the activated partial thromboplastin time (aPTT) assay	470:523	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	2	17	theme	thromboplastin	492:505	arg1	aPTT					513:516	aPTT	513:516	aPTT	513:516	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	3	18	theme	activation	625:634	arg1	system					636:641	the contact activation system	613:641	the contact activation system	613:641	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	1	19	theme	Acinetobacter	149:161	arg1	baumannii					163:171	Antibiotic-resistant Acinetobacter baumannii	128:171	Antibiotic-resistant Acinetobacter baumannii	128:171	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	19	theme	Acinetobacter	149:161	arg1	cause					205:209	a cause	203:209	a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia	203:308	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	7	20	theme	angioedema	1295:1304	arg1	type					1306:1309	hereditary angioedema type III	1284:1313	hereditary angioedema type III (HAEIII)	1284:1322	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	7	20	theme	angioedema	1295:1304	arg1	HAEIII					1316:1321	HAEIII	1316:1321	HAEIII	1316:1321	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	7	21	with	patients	1270:1277	arg1	type					1306:1309	hereditary angioedema type III	1284:1313	hereditary angioedema type III (HAEIII)	1284:1322	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	7	21	with	patients	1270:1277	arg1	HAEIII					1316:1321	HAEIII	1316:1321	HAEIII	1316:1321	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	9	22	theme	Ventilator-associated	1715:1735	arg1	infections					1810:1819	the most common and severe infections	1783:1819	the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1783:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	22	theme	Ventilator-associated	1715:1735	arg1	pneumonia					1737:1745	Ventilator-associated pneumonia	1715:1745	Ventilator-associated pneumonia	1715:1745	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	22	theme	Ventilator-associated	1715:1735	arg1	bacteremia					1768:1777	catheter-related bacteremia	1751:1777	catheter-related bacteremia	1751:1777	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	6	23	theme	glycosylated	1135:1146	arg1	threonine					1148:1156	an O-linked glycosylated threonine	1123:1156	an O-linked glycosylated threonine	1123:1156	At both sites, cleavage occurs between proline and an O-linked glycosylated threonine, and deglycosylation of fXII prevents cleavage by CpaA.
30563903	9	24	theme	proteins	1983:1990	arg1	contribution					1958:1969	the contribution	1954:1969	the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1954:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	0	25	theme	Acinetobacter	63:75	arg1	baumannii					77:85	Acinetobacter baumannii	63:85	Acinetobacter baumannii	63:85	CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.
30563903	5	26	theme	fXII	1066:1069	arg1	inactivation					1050:1061	inactivation	1050:1061	inactivation of fXII	1050:1069	In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII.
30563903	3	27	theme	human	647:651	arg1	plasma					671:676	human as well as murine plasma	647:676	human as well as murine plasma	647:676	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	9	28	theme	A.	1995:1996	arg1	survival					2008:2015	A. baumannii survival	1995:2015	A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1995:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	0	29	theme	Coagulation	104:114	arg1	XII					123:125	Coagulation Factor XII	104:125	Coagulation Factor XII	104:125	CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.
30563903	10	30	theme	growing	2349:2355	arg1	list					2357:2360	a small, but growing list	2336:2360	a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system	2336:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	10	31	theme	host	2445:2448	arg1	system					2458:2463	the host defense system	2441:2463	the host defense system	2441:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	9	32	theme	common	1792:1797	arg1	infections					1810:1819	the most common and severe infections	1783:1819	the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1783:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	32	theme	common	1792:1797	arg1	pneumonia					1737:1745	Ventilator-associated pneumonia	1715:1745	Ventilator-associated pneumonia	1715:1745	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	32	theme	common	1792:1797	arg1	bacteremia					1768:1777	catheter-related bacteremia	1751:1777	catheter-related bacteremia	1751:1777	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	4	33	theme	modified	750:757	arg1	assay					764:768	a modified aPTT assay	748:768	a modified aPTT assay	748:768	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	2	34	theme	human	442:446	arg1	plasma					448:453	human plasma	442:453	human plasma	442:453	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	9	35	theme	severe	1803:1808	arg1	infections					1810:1819	the most common and severe infections	1783:1819	the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1783:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	35	theme	severe	1803:1808	arg1	pneumonia					1737:1745	Ventilator-associated pneumonia	1715:1745	Ventilator-associated pneumonia	1715:1745	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	35	theme	severe	1803:1808	arg1	bacteremia					1768:1777	catheter-related bacteremia	1751:1777	catheter-related bacteremia	1751:1777	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	2	36	theme	activated	474:482	arg1	assay					519:523	the activated partial thromboplastin time (aPTT) assay	470:523	the activated partial thromboplastin time (aPTT) assay	470:523	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	10	37	theme	glycosylated	2414:2425	arg1	components					2427:2436	highly glycosylated components	2407:2436	highly glycosylated components of the host defense system	2407:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	9	38	theme	CpaA-mediated	2268:2280	arg1	inactivation					2282:2293	CpaA-mediated inactivation	2268:2293	CpaA-mediated inactivation of factor XII	2268:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	0	39	theme	Adamalysin-like	26:40	arg1	Protease					42:49	a Glycan-Specific Adamalysin-like Protease	8:49	a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII	8:125	CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.
30563903	0	39	theme	Adamalysin-like	26:40	arg1	CpaA					0:3	CpaA	0:3	CpaA	0:3	CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.
30563903	5	40	theme	fXII	982:985	arg1	region					966:971	the highly glycosylated proline-rich region	929:971	the highly glycosylated proline-rich region of human fXII	929:985	In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII.
30563903	7	41	theme	mutant	1236:1241	arg1	fXII					1243:1246	mutant fXII	1236:1246	mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII)	1236:1322	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	7	41	theme	mutant	1236:1241	arg1	fXII-Thr309Lys					1249:1262	fXII-Thr309Lys	1249:1262	fXII-Thr309Lys	1249:1262	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	3	42	theme	murine	664:669	arg1	plasma					671:676	human as well as murine plasma	647:676	human as well as murine plasma	647:676	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	8	43	with	individuals	1394:1404	arg1	HAEIII					1411:1416	HAEIII	1411:1416	HAEIII	1411:1416	This raises the possibility that individuals with HAEIII who harbor this mutation may be partially protected from A. baumannii infection if CpaA contributes to human disease.
30563903	8	44	theme	human	1521:1525	arg1	disease					1527:1533	human disease	1521:1533	human disease	1521:1533	This raises the possibility that individuals with HAEIII who harbor this mutation may be partially protected from A. baumannii infection if CpaA contributes to human disease.
30563903	3	45	theme	discernible	690:700	arg1	effect					702:707	no discernible effect	687:707	no discernible effect	687:707	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	4	46	theme	factor	803:808	arg1	XII					810:812	coagulation factor XII	791:812	coagulation factor XII (fXII)	791:819	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	4	46	theme	factor	803:808	arg1	target					826:831	a target	824:831	a target of CpaA	824:839	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	4	46	theme	factor	803:808	arg1	fXII					815:818	fXII	815:818	fXII	815:818	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	9	47	theme	XII	2305:2307	arg1	inactivation					2282:2293	CpaA-mediated inactivation	2268:2293	CpaA-mediated inactivation of factor XII	2268:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	8	48	dep	A.	1475:1476	arg1	baumannii					1478:1486	baumannii	1478:1486	baumannii	1478:1486	This raises the possibility that individuals with HAEIII who harbor this mutation may be partially protected from A. baumannii infection if CpaA contributes to human disease.
30563903	5	49	theme	proline-rich	953:964	arg1	region					966:971	the highly glycosylated proline-rich region	929:971	the highly glycosylated proline-rich region of human fXII	929:985	In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII.
30563903	3	50	theme	extrinsic	716:724	arg1	pathway					726:732	the extrinsic pathway	712:732	the extrinsic pathway	712:732	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	9	51	theme	antimicrobial	1587:1599	arg1	formation					1651:1659	intravascular thrombus formation	1628:1659	intravascular thrombus formation	1628:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	51	theme	antimicrobial	1587:1599	arg1	mechanisms					1609:1618	important antimicrobial defense mechanisms	1577:1618	important antimicrobial defense mechanisms such as intravascular thrombus formation	1577:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	10	52	gly	glycosylated	2414:2425	arg1	components					2427:2436	highly glycosylated components	2407:2436	highly glycosylated components of the host defense system	2407:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	3	53	theme	coagulation	580:590	arg1	pathway					592:598	the intrinsic coagulation pathway	566:598	the intrinsic coagulation pathway	566:598	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	9	54	theme	outer	1905:1909	arg1	OmpA					1926:1929	the outer membrane porin OmpA	1901:1929	the outer membrane porin OmpA	1901:1929	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	55	dep	Acinetobacter	1831:1843	arg1	known					1942:1946	known	1942:1946	is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1939:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	55	dep	Acinetobacter	1831:1843	arg1	baumannii					1845:1853	Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1831:2307	Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1831:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	56	theme	porin	1920:1924	arg1	OmpA					1926:1929	the outer membrane porin OmpA	1901:1929	the outer membrane porin OmpA	1901:1929	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	1	57	theme	difficult-to-treat	214:231	arg1	infections					283:292	wound infections	277:292	wound infections	277:292	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	57	theme	difficult-to-treat	214:231	arg1	bacteremia					299:308	bacteremia	299:308	bacteremia	299:308	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	57	theme	difficult-to-treat	214:231	arg1	infections					244:253	difficult-to-treat nosocomial infections	214:253	difficult-to-treat nosocomial infections	214:253	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	57	theme	difficult-to-treat	214:231	arg1	pneumonia					266:274	pneumonia	266:274	pneumonia	266:274	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	4	58	theme	CpaA	836:839	arg1	XII					810:812	coagulation factor XII	791:812	coagulation factor XII (fXII)	791:819	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	4	58	theme	CpaA	836:839	arg1	target					826:831	a target	824:831	a target of CpaA	824:839	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	7	59	theme	CpaA	1342:1345	arg1	inactivation					1347:1358	CpaA inactivation	1342:1358	CpaA inactivation	1342:1358	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	9	60	theme	factor	2162:2167	arg1	XII					2169:2171	coagulation factor XII	2150:2171	coagulation factor XII	2150:2171	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	60	theme	factor	2162:2167	arg1	target					2178:2183	a target	2176:2183	a target of CpaA	2176:2191	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	2	61	theme	metalloprotease	355:369	arg1	CpaA					371:374	the metalloprotease CpaA	351:374	the metalloprotease CpaA	351:374	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	9	62	dep	A.	1995:1996	arg1	baumannii					1998:2006	baumannii	1998:2006	baumannii	1998:2006	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	1	63	theme	infections	244:253	arg1	baumannii					163:171	Antibiotic-resistant Acinetobacter baumannii	128:171	Antibiotic-resistant Acinetobacter baumannii	128:171	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	63	theme	infections	244:253	arg1	cause					205:209	a cause	203:209	a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia	203:308	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	9	64	theme	thrombus	1642:1649	arg1	formation					1651:1659	intravascular thrombus formation	1628:1659	intravascular thrombus formation	1628:1659	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	10	65	theme	defense	2450:2456	arg1	system					2458:2463	the host defense system	2441:2463	the host defense system	2441:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	5	66	from	site	1026:1029	arg1	cleavage					1002:1009	cleavage	1002:1009	cleavage at the 308-309 site	1002:1029	In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII.
30563903	3	67	theme	contact	617:623	arg1	system					636:641	the contact activation system	613:641	the contact activation system	613:641	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	1	68	theme	Antibiotic-resistant	128:147	arg1	baumannii					163:171	Antibiotic-resistant Acinetobacter baumannii	128:171	Antibiotic-resistant Acinetobacter baumannii	128:171	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	1	68	theme	Antibiotic-resistant	128:147	arg1	cause					205:209	a cause	203:209	a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia	203:308	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	10	69	theme	proteases	2375:2383	arg1	list					2357:2360	a small, but growing list	2336:2360	a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system	2336:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	9	70	theme	acquired	2071:2078	arg1	CpaA					2042:2045	CpaA	2042:2045	CpaA	2042:2045	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	70	theme	acquired	2071:2078	arg1	factor					2090:2095	a potentially recently acquired virulence factor	2048:2095	a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	2048:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	71	theme	CpaA	2188:2191	arg1	XII					2169:2171	coagulation factor XII	2150:2171	coagulation factor XII	2150:2171	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	71	theme	CpaA	2188:2191	arg1	target					2178:2183	a target	2176:2183	a target of CpaA	2176:2191	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	2	72	theme	Previous	311:318	arg1	studies					320:326	Previous studies	311:326	Previous studies	311:326	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	9	73	theme	secreted	1974:1981	arg1	proteins					1983:1990	secreted proteins	1974:1990	secreted proteins	1974:1990	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	10	74	theme	small	2338:2342	arg1	list					2357:2360	a small, but growing list	2336:2360	a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system	2336:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	7	75	theme	hereditary	1284:1293	arg1	type					1306:1309	hereditary angioedema type III	1284:1313	hereditary angioedema type III (HAEIII)	1284:1322	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	7	75	theme	hereditary	1284:1293	arg1	HAEIII					1316:1321	HAEIII	1316:1321	HAEIII	1316:1321	Consistent with this, mutant fXII (fXII-Thr309Lys) from patients with hereditary angioedema type III (HAEIII) is protected from CpaA inactivation.
30563903	9	76	theme	cleavage	2202:2209	arg1	sites					2211:2215	the cleavage sites	2198:2215	the cleavage sites	2198:2215	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	77	theme	catheter-related	1751:1766	arg1	infections					1810:1819	the most common and severe infections	1783:1819	the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	1783:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	77	theme	catheter-related	1751:1766	arg1	pneumonia					1737:1745	Ventilator-associated pneumonia	1715:1745	Ventilator-associated pneumonia	1715:1745	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	77	theme	catheter-related	1751:1766	arg1	bacteremia					1768:1777	catheter-related bacteremia	1751:1777	catheter-related bacteremia	1751:1777	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	0	78	theme	Factor	116:121	arg1	XII					123:125	Coagulation Factor XII	104:125	Coagulation Factor XII	104:125	CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.
30563903	8	79	theme	A.	1475:1476	arg1	infection					1488:1496	A. baumannii infection	1475:1496	A. baumannii infection	1475:1496	This raises the possibility that individuals with HAEIII who harbor this mutation may be partially protected from A. baumannii infection if CpaA contributes to human disease.
30563903	2	80	theme	time	507:510	arg1	assay					519:523	the activated partial thromboplastin time (aPTT) assay	470:523	the activated partial thromboplastin time (aPTT) assay	470:523	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	0	81	theme	Glycan-Specific	10:24	arg1	Protease					42:49	a Glycan-Specific Adamalysin-like Protease	8:49	a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII	8:125	CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.
30563903	0	81	theme	Glycan-Specific	10:24	arg1	CpaA					0:3	CpaA	0:3	CpaA	0:3	CpaA Is a Glycan-Specific Adamalysin-like Protease Secreted by Acinetobacter baumannii That Inactivates Coagulation Factor XII.
30563903	2	82	theme	partial	484:490	arg1	time					507:510	partial thromboplastin time	484:510	the activated partial thromboplastin time (aPTT) assay	470:523	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	2	82	theme	partial	484:490	arg1	aPTT					513:516	aPTT	513:516	aPTT	513:516	Previous studies have demonstrated that the metalloprotease CpaA contributes to virulence and prolongs clotting time when added to human plasma as measured by the activated partial thromboplastin time (aPTT) assay.
30563903	4	83	theme	aPTT	759:762	arg1	assay					764:768	a modified aPTT assay	748:768	a modified aPTT assay	748:768	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	3	84	from	system	636:641	arg1	plasma					671:676	human as well as murine plasma	647:676	human as well as murine plasma	647:676	Here, we show that CpaA interferes with the intrinsic coagulation pathway, also called the contact activation system, in human as well as murine plasma, but has no discernible effect on the extrinsic pathway.
30563903	5	85	theme	human	976:980	arg1	fXII					982:985	human fXII	976:985	human fXII	976:985	In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII.
30563903	6	86	theme	O-linked	1126:1133	arg1	threonine					1148:1156	an O-linked glycosylated threonine	1123:1156	an O-linked glycosylated threonine	1123:1156	At both sites, cleavage occurs between proline and an O-linked glycosylated threonine, and deglycosylation of fXII prevents cleavage by CpaA.
30563903	5	87	gly	glycosylated	940:951	arg1	region					966:971	the highly glycosylated proline-rich region	929:971	the highly glycosylated proline-rich region of human fXII	929:985	In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII.
30563903	9	88	theme	factor	2298:2303	arg1	XII					2305:2307	factor XII	2298:2307	factor XII	2298:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	5	89	theme	glycosylated	940:951	arg1	region					966:971	the highly glycosylated proline-rich region	929:971	the highly glycosylated proline-rich region of human fXII	929:985	In addition, we map the cleavage by CpaA to two positions, 279-280 and 308-309, within the highly glycosylated proline-rich region of human fXII, and show that cleavage at the 308-309 site is responsible for inactivation of fXII.
30563903	9	90	theme	virulence	2080:2088	arg1	CpaA					2042:2045	CpaA	2042:2045	CpaA	2042:2045	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	9	90	theme	virulence	2080:2088	arg1	factor					2090:2095	a potentially recently acquired virulence factor	2048:2095	a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII	2048:2307	By inactivating fXII, CpaA may attenuate important antimicrobial defense mechanisms such as intravascular thrombus formation, thus allowing A. baumannii to disseminate.IMPORTANCE Ventilator-associated pneumonia and catheter-related bacteremia are the most common and severe infections caused by Acinetobacter baumannii Besides the capsule, lipopolysaccharides, and the outer membrane porin OmpA, little is known about the contribution of secreted proteins to A. baumannii survival in vivo Here we focus on CpaA, a potentially recently acquired virulence factor that inhibits blood coagulation in vitro We identify coagulation factor XII as a target of CpaA, map the cleavage sites, and show that glycosylation is a prerequisite for CpaA-mediated inactivation of factor XII.
30563903	4	91	theme	coagulation	791:801	arg1	XII					810:812	coagulation factor XII	791:812	coagulation factor XII (fXII)	791:819	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	4	91	theme	coagulation	791:801	arg1	target					826:831	a target	824:831	a target of CpaA	824:839	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	4	91	theme	coagulation	791:801	arg1	fXII					815:818	fXII	815:818	fXII	815:818	By utilizing a modified aPTT assay, we demonstrate that coagulation factor XII (fXII) is a target of CpaA.
30563903	1	92	theme	wound	277:281	arg1	infections					283:292	wound infections	277:292	wound infections	277:292	Antibiotic-resistant Acinetobacter baumannii is increasingly recognized as a cause of difficult-to-treat nosocomial infections, including pneumonia, wound infections, and bacteremia.
30563903	10	93	theme	bacterial	2365:2373	arg1	proteases					2375:2383	bacterial proteases	2365:2383	bacterial proteases that are specific for highly glycosylated components of the host defense system	2365:2463	We propose adding CpaA to a small, but growing list of bacterial proteases that are specific for highly glycosylated components of the host defense system.
30563903	6	94	link	O-linked	1126:1133	arg1	threonine					1148:1156	an O-linked glycosylated threonine	1123:1156	an O-linked glycosylated threonine	1123:1156	At both sites, cleavage occurs between proline and an O-linked glycosylated threonine, and deglycosylation of fXII prevents cleavage by CpaA.
30137291	2	0	theme	environmental	317:329	arg1	stresses					331:338	environmental stresses	317:338	environmental stresses often experienced on lower-grade agricultural land	317:389	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	9	1	from	differences	1962:1972	arg1	release					2001:2007	cell-wall biomass sugar release	1977:2007	cell-wall biomass sugar release	1977:2007	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	5	2	dep	assays	1055:1060	arg1	measure					1066:1072	measure	1066:1072	to measure sugar release	1063:1086	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	9	3	with	association	1910:1920	arg1	lignin					1927:1932	lignin	1927:1932	lignin	1927:1932	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	6	4	theme	genotype	1284:1291	arg1	Gig-311					1293:1299	the M. × giganteus genotype Gig-311	1265:1299	the M. × giganteus genotype Gig-311	1265:1299	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	3	5	theme	nutrient	535:542	arg1	stress					544:549	nutrient stress	535:549	nutrient stress	535:549	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	8	6	theme	drought	1724:1730	arg1	conditions					1750:1759	drought and nutrient-rich conditions	1724:1759	drought and nutrient-rich conditions	1724:1759	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	4	7	theme	separate	830:837	arg1	stresses					857:864	separate and combinatorial stresses	830:864	separate and combinatorial stresses	830:864	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	2	8	from	impact	307:312	arg1	traits					412:417	cell-wall quality traits	394:417	cell-wall quality traits in miscanthus biomass crops	394:445	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	9	9	theme	observed	1953:1960	arg1	differences					1962:1972	the observed differences	1949:1972	the observed differences in cell-wall biomass sugar release	1949:2007	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	6	10	theme	×	1272:1272	arg1	Gig-311					1293:1299	the M. × giganteus genotype Gig-311	1265:1299	the M. × giganteus genotype Gig-311	1265:1299	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	9	11	theme	polysaccharides	1845:1859	arg1	structure					1822:1830	fine structure	1817:1830	fine structure of cell-wall polysaccharides, including heteroxylans and pectins	1817:1895	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	8	12	theme	nutrient-rich	1736:1748	arg1	conditions					1750:1759	drought and nutrient-rich conditions	1724:1759	drought and nutrient-rich conditions	1724:1759	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	7	13	theme	different	1466:1474	arg1	conditions					1490:1499	the different environmental conditions	1462:1499	the different environmental conditions	1462:1499	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	4	14	theme	combinatorial	843:855	arg1	stresses					857:864	separate and combinatorial stresses	830:864	separate and combinatorial stresses	830:864	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	6	15	theme	sacchariflorus	1168:1181	arg1	Sac-5					1192:1196	the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11	1161:1245	Sac-5	1192:1196	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	7	16	theme	biomass	1407:1413	arg1	measure					1423:1429	a biomass quality measure	1405:1429	a biomass quality measure	1405:1429	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	9	17	theme	biomass	1987:1993	arg1	release					2001:2007	cell-wall biomass sugar release	1977:2007	cell-wall biomass sugar release	1977:2007	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	5	18	theme	sugar	1074:1078	arg1	release					1080:1086	sugar release	1074:1086	sugar release	1074:1086	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	4	19	used	used	770:773	arg2	METHODS					670:676	METHODS	670:676	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth)	670:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	6	20	theme	nutrient-poor	1335:1347	arg1	compost					1349:1355	nutrient-poor compost	1335:1355	nutrient-poor compost	1335:1355	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	9	21	theme	Cell-wall	1762:1770	arg1	analyses					1784:1791	Cell-wall composition analyses	1762:1791	Cell-wall composition analyses	1762:1791	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	6	22	theme	genotype	1231:1238	arg1	Sin-11					1240:1245	the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11	1161:1245	Sin-11	1240:1245	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	7	23	theme	enzymatic	1375:1383	arg1	hydrolysis					1385:1394	enzymatic hydrolysis	1375:1394	enzymatic hydrolysis	1375:1394	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	10	24	theme	miscanthus	2080:2089	arg1	measures					2107:2114	miscanthus biomass quality measures	2080:2114	miscanthus biomass quality measures	2080:2114	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	8	25	from	leaves	1646:1651	arg1	release					1633:1639	the highest sugar release	1615:1639	the highest sugar release from leaves	1615:1651	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	5	26	theme	genotypes	923:931	arg1	samples					891:897	Harvested leaf and stem samples	867:897	samples	891:897	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	5	26	theme	genotypes	923:931	arg1	leaf					877:880	Harvested leaf and stem samples	867:897	leaf	877:880	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	6	27	theme	M.	1219:1220	arg1	Sin-11					1240:1245	the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11	1161:1245	Sin-11	1240:1245	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	1	28	theme	biomass	140:146	arg1	crops					148:152	dedicated biomass crops	130:152	dedicated biomass crops	130:152	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	1	28	theme	biomass	140:146	arg1	miscanthus					165:174	miscanthus	165:174	miscanthus	165:174	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	1	29	dep	BACKGROUND	91:100	arg1	provides					194:201	provides	194:201	provides a promising approach to the reduction of dependency on fossil fuels	194:269	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	10	30	theme	assessment	2066:2075	arg1	importance					2048:2057	the importance	2044:2057	the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions	2044:2261	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	5	31	theme	stem	886:889	arg1	samples					891:897	Harvested leaf and stem samples	867:897	samples	891:897	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	4	32	theme	Automated	678:686	arg1	METHODS					670:676	METHODS	670:676	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth)	670:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	10	33	theme	quality	2099:2105	arg1	measures					2107:2114	miscanthus biomass quality measures	2080:2114	miscanthus biomass quality measures	2080:2114	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	5	34	theme	cell-wall	1093:1101	arg1	analyses					1115:1122	cell-wall composition analyses	1093:1122	cell-wall composition analyses	1093:1122	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	1	35	from	cultivation	115:125	arg1	land					189:192	marginal land	180:192	marginal land	180:192	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	7	36	theme	Sugar	1358:1362	arg1	release					1364:1370	Sugar release	1358:1370	Sugar release	1358:1370	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	9	37	theme	cell-wall	1835:1843	arg1	pectins					1889:1895	pectins	1889:1895	pectins	1889:1895	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	9	37	theme	cell-wall	1835:1843	arg1	polysaccharides					1845:1859	cell-wall polysaccharides	1835:1859	cell-wall polysaccharides	1835:1859	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	9	37	theme	cell-wall	1835:1843	arg1	heteroxylans					1872:1883	heteroxylans	1872:1883	heteroxylans	1872:1883	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	4	38	theme	Plant	723:727	arg1	NPPC-Aberystwyth					747:762	NPPC-Aberystwyth	747:762	NPPC-Aberystwyth	747:762	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	4	38	theme	Plant	723:727	arg1	Centre					739:744	the National Plant Phenomics Centre	710:744	the National Plant Phenomics Centre (NPPC-Aberystwyth)	710:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	2	39	theme	lower-grade	361:371	arg1	land					386:389	lower-grade agricultural land	361:389	lower-grade agricultural land	361:389	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	1	40	theme	fossil	258:263	arg1	fuels					265:269	fossil fuels	258:269	fossil fuels	258:269	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	2	41	theme	miscanthus	422:431	arg1	crops					441:445	miscanthus biomass crops	422:445	miscanthus biomass crops	422:445	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	8	42	theme	abundant	1570:1577	arg1	water					1579:1583	abundant water	1570:1583	abundant water	1570:1583	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	0	43	theme	drought	13:19	arg1	stress					21:26	drought stress	13:26	drought stress	13:26	Nutrient and drought stress: implications for phenology and biomass quality in miscanthus.
30137291	10	44	theme	suitable	2194:2201	arg1	genotypes					2214:2222	suitable miscanthus genotypes	2194:2222	suitable miscanthus genotypes	2194:2222	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	2	45	theme	cell-wall	394:402	arg1	traits					412:417	cell-wall quality traits	394:417	cell-wall quality traits in miscanthus biomass crops	394:445	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	8	46	theme	nutrients	1593:1601	arg1	combination					1555:1565	A combination	1553:1565	A combination of abundant water and low nutrients	1553:1601	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	3	47	theme	different	469:477	arg1	genotypes					490:498	three different miscanthus genotypes	463:498	three different miscanthus genotypes	463:498	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	7	48	theme	organ-dependent	1529:1543	arg1	manner					1545:1550	a stress-, genotype- and organ-dependent manner	1504:1550	a stress-, genotype- and organ-dependent manner	1504:1550	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	5	49	theme	saccharification	1038:1053	arg1	assays					1055:1060	saccharification assays	1038:1060	saccharification assays	1038:1060	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	3	50	theme	cell-wall	648:656	arg1	properties					658:667	cell-wall properties	648:667	cell-wall properties	648:667	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	6	51	dep	RESULTS	1129:1135	arg1	showed					1149:1154	showed	1149:1154	showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost	1149:1355	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	1	52	theme	promising	205:213	arg1	approach					215:222	a promising approach	203:222	a promising approach to the reduction of dependency on fossil fuels	203:269	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	7	53	theme	genotype-	1515:1523	arg1	manner					1545:1550	a stress-, genotype- and organ-dependent manner	1504:1550	a stress-, genotype- and organ-dependent manner	1504:1550	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	6	54	theme	KEY	1125:1127	arg1	RESULTS					1129:1135	KEY RESULTS	1125:1135	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.	1125:1356	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	8	55	theme	highest	1619:1625	arg1	release					1633:1639	the highest sugar release	1615:1639	the highest sugar release from leaves	1615:1651	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	7	56	theme	stress-	1506:1512	arg1	manner					1545:1550	a stress-, genotype- and organ-dependent manner	1504:1550	a stress-, genotype- and organ-dependent manner	1504:1550	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	0	57	dep	Nutrient	0:7	arg1	implications					29:40	implications	29:40	Nutrient and drought stress: implications for phenology and biomass quality in miscanthus.	0:89	Nutrient and drought stress: implications for phenology and biomass quality in miscanthus.
30137291	2	58	from	traits	412:417	arg1	crops					441:445	miscanthus biomass crops	422:445	miscanthus biomass crops	422:445	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	6	59	theme	drought	1306:1312	arg1	stress					1314:1319	drought stress	1306:1319	drought stress	1306:1319	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	2	60	theme	stresses	331:338	arg1	impact					307:312	the impact	303:312	the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops	303:445	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	1	61	theme	dependency	244:253	arg1	reduction					231:239	the reduction	227:239	the reduction of dependency on fossil fuels	227:269	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	7	62	theme	environmental	1476:1488	arg1	conditions					1490:1499	the different environmental conditions	1462:1499	the different environmental conditions	1462:1499	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	3	63	dep	both	552:555	arg1	separately					557:566	separately	557:566	separately	557:566	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	10	64	theme	miscanthus	2203:2212	arg1	genotypes					2214:2222	suitable miscanthus genotypes	2194:2222	suitable miscanthus genotypes	2194:2222	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	3	65	from	impact	621:626	arg1	growth					637:642	plant growth	631:642	plant growth	631:642	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	3	65	from	impact	621:626	arg1	properties					658:667	cell-wall properties	648:667	cell-wall properties	648:667	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	6	66	theme	giganteus	1274:1282	arg1	Gig-311					1293:1299	the M. × giganteus genotype Gig-311	1265:1299	the M. × giganteus genotype Gig-311	1265:1299	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	3	67	theme	drought	516:522	arg1	stress					524:529	drought stress	516:529	drought stress	516:529	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	6	68	theme	genotype	1183:1190	arg1	Sac-5					1192:1196	the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11	1161:1245	Sac-5	1192:1196	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	6	69	theme	M.	1269:1270	arg1	Gig-311					1293:1299	the M. × giganteus genotype Gig-311	1265:1299	the M. × giganteus genotype Gig-311	1265:1299	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	5	70	theme	Harvested	867:875	arg1	leaf					877:880	Harvested leaf and stem samples	867:897	leaf	877:880	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	10	71	dep	yield	2139:2143	arg1	determinations					2145:2158	determinations	2145:2158	determinations	2145:2158	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	6	72	theme	M.	1165:1166	arg1	Sac-5					1192:1196	the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11	1161:1245	Sac-5	1192:1196	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	9	73	theme	cell-wall	1977:1985	arg1	release					2001:2007	cell-wall biomass sugar release	1977:2007	cell-wall biomass sugar release	1977:2007	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	8	74	theme	conditions	1750:1759	arg1	combination					1709:1719	the combination	1705:1719	the combination of drought and nutrient-rich conditions	1705:1759	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	1	75	theme	marginal	180:187	arg1	land					189:192	marginal land	180:192	marginal land	180:192	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	7	76	theme	quality	1415:1421	arg1	measure					1423:1429	a biomass quality measure	1405:1429	a biomass quality measure	1405:1429	Sugar release by enzymatic hydrolysis, used as a biomass quality measure, was significantly affected by the different environmental conditions in a stress-, genotype- and organ-dependent manner.
30137291	9	77	theme	sugar	1995:1999	arg1	release					2001:2007	cell-wall biomass sugar release	1977:2007	cell-wall biomass sugar release	1977:2007	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	1	78	from	reduction	231:239	arg1	fuels					265:269	fossil fuels	258:269	fossil fuels	258:269	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	9	79	from	changes	1806:1812	arg1	association					1910:1920	association	1910:1920	association with lignin	1910:1932	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	9	79	from	changes	1806:1812	arg1	structure					1822:1830	fine structure	1817:1830	fine structure of cell-wall polysaccharides, including heteroxylans and pectins	1817:1895	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	4	80	theme	imaging	688:694	arg1	facilities					696:705	imaging facilities	688:705	imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth)	688:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	5	81	theme	miscanthus	912:921	arg1	genotypes					923:931	the three miscanthus genotypes	902:931	the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus)	902:1007	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	9	82	theme	composition	1772:1782	arg1	analyses					1784:1791	Cell-wall composition analyses	1762:1791	Cell-wall composition analyses	1762:1791	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	6	83	theme	sinensis	1222:1229	arg1	Sin-11					1240:1245	the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11	1161:1245	Sin-11	1240:1245	KEY RESULTS Phenotyping showed that the M. sacchariflorus genotype Sac-5 and particularly the M. sinensis genotype Sin-11 coped better than the M. × giganteus genotype Gig-311 with drought stress when grown in nutrient-poor compost.
30137291	10	84	theme	different	2228:2236	arg1	conditions					2252:2261	different environmental conditions	2228:2261	different environmental conditions	2228:2261	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	0	85	theme	biomass	60:66	arg1	quality					68:74	biomass quality	60:74	biomass quality	60:74	Nutrient and drought stress: implications for phenology and biomass quality in miscanthus.
30137291	1	86	theme	dedicated	130:138	arg1	crops					148:152	dedicated biomass crops	130:152	dedicated biomass crops	130:152	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	1	86	theme	dedicated	130:138	arg1	miscanthus					165:174	miscanthus	165:174	miscanthus	165:174	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	1	87	theme	crops	148:152	arg1	cultivation					115:125	The cultivation	111:125	The cultivation of dedicated biomass crops, including miscanthus, on marginal land	111:192	BACKGROUND AND AIMS The cultivation of dedicated biomass crops, including miscanthus, on marginal land provides a promising approach to the reduction of dependency on fossil fuels.
30137291	10	88	theme	measures	2107:2114	arg1	assessment					2066:2075	the assessment	2062:2075	the assessment of miscanthus biomass quality measures	2062:2114	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	4	89	dep	Automated	678:686	arg1	facilities					696:705	imaging facilities	688:705	imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth)	688:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	9	90	theme	fine	1817:1820	arg1	structure					1822:1830	fine structure	1817:1830	fine structure of cell-wall polysaccharides, including heteroxylans and pectins	1817:1895	Cell-wall composition analyses suggest that changes in fine structure of cell-wall polysaccharides, including heteroxylans and pectins, possibly in association with lignin, contribute to the observed differences in cell-wall biomass sugar release.
30137291	10	91	dep	CONCLUSIONS	2010:2020	arg1	highlight					2034:2042	highlight	2034:2042	highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions	2034:2261	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	5	92	dep	genotypes	923:931	arg1	sinensis					945:952	Miscanthus sinensis	934:952	Miscanthus sinensis	934:952	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	5	92	dep	genotypes	923:931	arg1	sacchariflorus					966:979	Miscanthus sacchariflorus	955:979	Miscanthus sacchariflorus	955:979	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	5	92	dep	genotypes	923:931	arg1	giganteus					998:1006	Miscanthus × giganteus	985:1006	Miscanthus × giganteus	985:1006	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	10	93	theme	biomass	2091:2097	arg1	measures					2107:2114	miscanthus biomass quality measures	2080:2114	miscanthus biomass quality measures	2080:2114	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	5	94	theme	composition	1103:1113	arg1	analyses					1115:1122	cell-wall composition analyses	1093:1122	cell-wall composition analyses	1093:1122	Harvested leaf and stem samples of the three miscanthus genotypes (Miscanthus sinensis, Miscanthus sacchariflorus and Miscanthus × giganteus) were separately subjected to saccharification assays, to measure sugar release, and cell-wall composition analyses.
30137291	0	95	from	implications	29:40	arg1	miscanthus					79:88	miscanthus	79:88	miscanthus	79:88	Nutrient and drought stress: implications for phenology and biomass quality in miscanthus.
30137291	2	96	theme	agricultural	373:384	arg1	land					386:389	lower-grade agricultural land	361:389	lower-grade agricultural land	361:389	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	2	97	theme	biomass	433:439	arg1	crops					441:445	miscanthus biomass crops	422:445	miscanthus biomass crops	422:445	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	8	98	theme	water	1579:1583	arg1	combination					1555:1565	A combination	1553:1565	A combination of abundant water and low nutrients	1553:1601	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	4	99	theme	National	714:721	arg1	NPPC-Aberystwyth					747:762	NPPC-Aberystwyth	747:762	NPPC-Aberystwyth	747:762	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	4	99	theme	National	714:721	arg1	Centre					739:744	the National Plant Phenomics Centre	710:744	the National Plant Phenomics Centre (NPPC-Aberystwyth)	710:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	3	100	dep	exposed	505:511	arg1	combination					575:585	combination	575:585	combination	575:585	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	3	100	dep	exposed	505:511	arg1	aim					597:599	the aim	593:599	the aim of evaluating their impact on plant growth and cell-wall properties	593:667	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	3	100	dep	exposed	505:511	arg1	both					552:555	both	552:555	both	552:555	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	8	101	theme	low	1589:1591	arg1	nutrients					1593:1601	low nutrients	1589:1601	low nutrients	1589:1601	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	4	102	theme	Phenomics	729:737	arg1	NPPC-Aberystwyth					747:762	NPPC-Aberystwyth	747:762	NPPC-Aberystwyth	747:762	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	4	102	theme	Phenomics	729:737	arg1	Centre					739:744	the National Plant Phenomics Centre	710:744	the National Plant Phenomics Centre (NPPC-Aberystwyth)	710:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	2	103	theme	quality	404:410	arg1	traits					412:417	cell-wall quality traits	394:417	cell-wall quality traits in miscanthus biomass crops	394:445	However, little is known about the impact of environmental stresses often experienced on lower-grade agricultural land on cell-wall quality traits in miscanthus biomass crops.
30137291	4	104	theme	plant	811:815	arg1	responses					817:825	plant responses	811:825	plant responses to separate and combinatorial stresses	811:864	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	3	105	theme	miscanthus	479:488	arg1	genotypes					490:498	three different miscanthus genotypes	463:498	three different miscanthus genotypes	463:498	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	4	106	from	Centre	739:744	arg1	facilities					696:705	imaging facilities	688:705	imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth)	688:763	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
30137291	10	107	dep	different	2228:2236	arg1	environmental					2238:2250	environmental	2238:2250	environmental	2238:2250	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	10	108	theme	biomass	2131:2137	arg1	yield					2139:2143	biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions	2131:2261	yield	2139:2143	CONCLUSIONS The results highlight the importance of the assessment of miscanthus biomass quality measures in addition to biomass yield determinations and the requirement for selecting suitable miscanthus genotypes for different environmental conditions.
30137291	8	109	theme	sugar	1627:1631	arg1	release					1633:1639	the highest sugar release	1615:1639	the highest sugar release from leaves	1615:1651	A combination of abundant water and low nutrients resulted in the highest sugar release from leaves, while for stems this was generally associated with the combination of drought and nutrient-rich conditions.
30137291	3	110	theme	plant	631:635	arg1	growth					637:642	plant growth	631:642	plant growth	631:642	In this study, three different miscanthus genotypes were exposed to drought stress and nutrient stress, both separately and in combination, with the aim of evaluating their impact on plant growth and cell-wall properties.
30137291	4	111	theme	dynamic	779:785	arg1	phenotyping					787:797	dynamic phenotyping	779:797	dynamic phenotyping	779:797	METHODS Automated imaging facilities at the National Plant Phenomics Centre (NPPC-Aberystwyth) were used for dynamic phenotyping to identify plant responses to separate and combinatorial stresses.
31054469	4	0	theme	wood	551:554	arg1	properties					556:565	wood properties	551:565	wood properties	551:565	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	2	1	theme	wood	326:329	arg1	wall					336:339	the wood cell wall	322:339	the wood cell wall	322:339	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	10	2	contain	had	1606:1608	arg2	stiffness					1618:1626	similar stiffness	1610:1626	similar stiffness	1610:1626	However, the Pto4CL1-modified trees had similar stiffness to the control group.
31054469	10	2	contain	had	1606:1608	arg1	trees					1600:1604	the Pto4CL1-modified trees	1579:1604	the Pto4CL1-modified trees	1579:1604	However, the Pto4CL1-modified trees had similar stiffness to the control group.
31054469	2	3	theme	certain	364:370	arg1	enzymes					392:398	certain lignin biosynthesis enzymes	364:398	certain lignin biosynthesis enzymes	364:398	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	4	4	theme	poplar	639:644	arg1	walls					651:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	9	5	from	reduction	1451:1459	arg1	content					1471:1477	lignin content	1464:1477	lignin content	1464:1477	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	4	6	theme	walls	651:655	arg1	anatomy					600:606	anatomy	600:606	anatomy	600:606	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	4	6	theme	walls	651:655	arg1	composition					584:594	composition	584:594	composition	584:594	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	1	7	theme	physical	181:188	arg1	properties					205:214	the physical and mechanical properties	177:214	the physical and mechanical properties of plants	177:224	Cell wall components and structure impact the physical and mechanical properties of plants, thereby affecting wood applications.
31054469	9	8	theme	wood	1517:1520	arg1	strength					1522:1529	wood strength	1517:1529	wood strength	1517:1529	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	11	9	theme	impact	1723:1728	arg1	toughness					1730:1738	impact toughness	1723:1738	impact toughness in the low-lignin events	1723:1763	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	0	10	theme	transgenic	105:114	arg1	tomentosa					124:132	perennial transgenic Populus tomentosa	95:132	perennial transgenic Populus tomentosa	95:132	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	5	11	theme	Pto4CL1	802:808	arg1	up-regulation					785:797	the up-regulation	781:797	the up-regulation of Pto4CL1	781:808	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	11	12	from	increase	1711:1718	arg1	toughness					1730:1738	impact toughness	1723:1738	impact toughness in the low-lignin events	1723:1763	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	11	12	from	increase	1711:1718	arg1	shrinkage					1697:1705	volume shrinkage	1690:1705	volume shrinkage	1690:1705	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	4	13	theme	5-year-old	611:620	arg1	walls					651:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	0	14	theme	tomentosa	124:132	arg1	components					61:70	cell wall components	51:70	cell wall components	51:70	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	0	14	theme	tomentosa	124:132	arg1	properties					81:90	wood properties	76:90	wood properties	76:90	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	11	15	theme	low-lignin	1747:1756	arg1	events					1758:1763	the low-lignin events	1743:1763	the low-lignin events	1743:1763	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	4	16	dep	composition	584:594	arg1	the					580:582	the	580:582	the	580:582	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	8	17	theme	wood	1422:1425	arg1	density					1427:1433	slightly increased wood density	1403:1433	slightly increased wood density	1403:1433	Moreover, the increased lignin content caused significantly increased wood strength and slightly increased wood density.
31054469	7	18	theme	secondary	1294:1302	arg1	wall					1309:1312	the secondary cell wall	1290:1312	the secondary cell wall	1290:1312	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	4	19	theme	volume	691:696	arg1	shrinkage					698:706	volume shrinkage	691:706	volume shrinkage	691:706	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	1	20	theme	wall	140:143	arg1	components					145:154	Cell wall components	135:154	Cell wall components	135:154	Cell wall components and structure impact the physical and mechanical properties of plants, thereby affecting wood applications.
31054469	11	21	theme	significant	1666:1676	arg1	decrease					1678:1685	a significant decrease	1664:1685	a significant decrease in volume shrinkage	1664:1705	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	0	22	theme	cell	51:54	arg1	components					61:70	cell wall components	51:70	cell wall components	51:70	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	9	23	theme	lignin	1464:1469	arg1	content					1471:1477	lignin content	1464:1477	lignin content	1464:1477	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	0	24	from	impact	15:20	arg1	components					61:70	cell wall components	51:70	cell wall components	51:70	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	0	24	from	impact	15:20	arg1	properties					81:90	wood properties	76:90	wood properties	76:90	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	12	25	theme	walls	1859:1863	arg1	composition					1833:1843	the chemical composition	1820:1843	the chemical composition of plant cell walls	1820:1863	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	0	26	theme	wood	76:79	arg1	properties					81:90	wood properties	76:90	wood properties	76:90	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	4	27	theme	transgenic	737:746	arg1	trees					748:752	the transgenic trees	733:752	the transgenic trees	733:752	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	2	28	theme	biosynthesis	379:390	arg1	enzymes					392:398	certain lignin biosynthesis enzymes	364:398	certain lignin biosynthesis enzymes	364:398	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	7	29	theme	lignin	1280:1285	arg1	concentration					1263:1275	concentration	1263:1275	concentration	1263:1275	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	7	29	theme	lignin	1280:1285	arg1	deposition					1248:1257	deposition	1248:1257	deposition	1248:1257	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	3	30	theme	coenzyme	414:421	arg1	ligase					425:430	coenzyme A ligase	414:430	coenzyme A ligase(4CL)	414:435	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	30	theme	coenzyme	414:421	arg1	enzyme					473:478	an important lignin biosynthesis enzyme	440:478	an important lignin biosynthesis enzyme	440:478	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	30	theme	coenzyme	414:421	arg1	4-Coumarate					401:411	4-Coumarate	401:411	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.	401:479	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	30	theme	coenzyme	414:421	arg1	4CL					432:434	4CL	432:434	4CL	432:434	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	12	31	theme	plant	1848:1852	arg1	walls					1859:1863	plant cell walls	1848:1863	plant cell walls	1848:1863	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	0	32	dep	components	61:70	arg1	the					47:49	the	47:49	the	47:49	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	9	33	from	decrease	1544:1551	arg1	density					1561:1567	wood density	1556:1567	wood density	1556:1567	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	9	33	from	decrease	1544:1551	arg1	strength					1522:1529	wood strength	1517:1529	wood strength	1517:1529	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	6	34	theme	Pto4CL1	1011:1017	arg1	down-regulation					992:1006	the down-regulation	988:1006	the down-regulation of Pto4CL1	988:1017	In contrast, the down-regulation of Pto4CL1 resulted in a reduction in lignin content to 27.39%, and the content of cellulose and hemi-cellulose showed compensatory variation.
31054469	4	35	theme	impact	713:718	arg1	toughness					720:728	impact toughness	713:728	impact toughness	713:728	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	8	36	theme	increased	1329:1337	arg1	content					1346:1352	the increased lignin content	1325:1352	the increased lignin content	1325:1352	Moreover, the increased lignin content caused significantly increased wood strength and slightly increased wood density.
31054469	10	37	theme	similar	1610:1616	arg1	stiffness					1618:1626	similar stiffness	1610:1626	similar stiffness	1610:1626	However, the Pto4CL1-modified trees had similar stiffness to the control group.
31054469	0	38	theme	Pto4CL1	25:31	arg1	regulation					33:42	Pto4CL1 regulation	25:42	Pto4CL1 regulation	25:42	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	9	39	theme	slight	1537:1542	arg1	decrease					1544:1551	a slight decrease	1535:1551	a slight decrease in wood density	1535:1567	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	3	40	theme	biosynthesis	460:471	arg1	ligase					425:430	coenzyme A ligase	414:430	coenzyme A ligase(4CL)	414:435	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	40	theme	biosynthesis	460:471	arg1	enzyme					473:478	an important lignin biosynthesis enzyme	440:478	an important lignin biosynthesis enzyme	440:478	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	40	theme	biosynthesis	460:471	arg1	4-Coumarate					401:411	4-Coumarate	401:411	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.	401:479	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	4	41	from	impact	500:505	arg1	properties					556:565	wood properties	551:565	wood properties	551:565	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	4	41	from	impact	500:505	arg1	poplar					541:546	poplar	541:546	poplar	541:546	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	3	42	theme	important	443:451	arg1	ligase					425:430	coenzyme A ligase	414:430	coenzyme A ligase(4CL)	414:435	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	42	theme	important	443:451	arg1	enzyme					473:478	an important lignin biosynthesis enzyme	440:478	an important lignin biosynthesis enzyme	440:478	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	42	theme	important	443:451	arg1	4-Coumarate					401:411	4-Coumarate	401:411	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.	401:479	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	10	43	theme	control	1635:1641	arg1	group					1643:1647	the control group	1631:1647	the control group	1631:1647	However, the Pto4CL1-modified trees had similar stiffness to the control group.
31054469	1	44	theme	plants	219:224	arg1	properties					205:214	the physical and mechanical properties	177:214	the physical and mechanical properties of plants	177:224	Cell wall components and structure impact the physical and mechanical properties of plants, thereby affecting wood applications.
31054469	7	45	theme	transgenic	1210:1219	arg1	events					1221:1226	the transgenic events	1206:1226	the transgenic events	1206:1226	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	8	46	theme	wood	1385:1388	arg1	strength					1390:1397	significantly increased wood strength	1361:1397	significantly increased wood strength	1361:1397	Moreover, the increased lignin content caused significantly increased wood strength and slightly increased wood density.
31054469	6	47	from	reduction	1033:1041	arg1	content					1053:1059	lignin content	1046:1059	lignin content	1046:1059	In contrast, the down-regulation of Pto4CL1 resulted in a reduction in lignin content to 27.39%, and the content of cellulose and hemi-cellulose showed compensatory variation.
31054469	7	48	dep	deposition	1248:1257	arg1	the					1244:1246	the	1244:1246	the	1244:1246	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	6	49	theme	lignin	1046:1051	arg1	content					1053:1059	lignin content	1046:1059	lignin content	1046:1059	In contrast, the down-regulation of Pto4CL1 resulted in a reduction in lignin content to 27.39%, and the content of cellulose and hemi-cellulose showed compensatory variation.
31054469	1	50	theme	wood	245:248	arg1	applications					250:261	wood applications	245:261	wood applications	245:261	Cell wall components and structure impact the physical and mechanical properties of plants, thereby affecting wood applications.
31054469	7	51	from	change	1186:1191	arg1	lignin					1196:1201	lignin	1196:1201	lignin	1196:1201	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	7	51	from	change	1186:1191	arg1	events					1221:1226	the transgenic events	1206:1226	the transgenic events	1206:1226	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	2	52	theme	abundant	283:290	arg1	biopolymer					292:301	the most abundant biopolymer	274:301	the most abundant biopolymer after cellulose in the wood cell wall	274:339	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	2	52	theme	abundant	283:290	arg1	Lignin					264:269	Lignin	264:269	Lignin	264:269	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	2	53	mod	modified	352:359	arg3	enzymes					392:398	certain lignin biosynthesis enzymes	364:398	certain lignin biosynthesis enzymes	364:398	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	2	53	mod	modified	352:359	arg1	biopolymer					292:301	the most abundant biopolymer	274:301	the most abundant biopolymer after cellulose in the wood cell wall	274:339	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	2	53	mod	modified	352:359	arg1	Lignin					264:269	Lignin	264:269	Lignin	264:269	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	12	54	theme	wood	1936:1939	arg1	properties					1918:1927	the physical and mechanical properties	1890:1927	the physical and mechanical properties of the wood	1890:1939	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	6	55	theme	hemi-cellulose	1105:1118	arg1	content					1080:1086	the content	1076:1086	the content of cellulose and hemi-cellulose	1076:1118	In contrast, the down-regulation of Pto4CL1 resulted in a reduction in lignin content to 27.39%, and the content of cellulose and hemi-cellulose showed compensatory variation.
31054469	9	56	from	decrease	1505:1512	arg1	density					1561:1567	wood density	1556:1567	wood density	1556:1567	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	9	56	from	decrease	1505:1512	arg1	strength					1522:1529	wood strength	1517:1529	wood strength	1517:1529	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	5	57	theme	lignin	824:829	arg1	content					831:837	the lignin content	820:837	the lignin content	820:837	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	11	58	from	toughness	1730:1738	arg1	events					1758:1763	the low-lignin events	1743:1763	the low-lignin events	1743:1763	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	6	59	theme	cellulose	1091:1099	arg1	content					1080:1086	the content	1076:1086	the content of cellulose and hemi-cellulose	1076:1118	In contrast, the down-regulation of Pto4CL1 resulted in a reduction in lignin content to 27.39%, and the content of cellulose and hemi-cellulose showed compensatory variation.
31054469	4	60	theme	Pto4CL1-modified	622:637	arg1	walls					651:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	12	61	theme	mechanical	1907:1916	arg1	properties					1918:1927	the physical and mechanical properties	1890:1927	the physical and mechanical properties of the wood	1890:1939	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	4	62	theme	cell	646:649	arg1	walls					651:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	5-year-old Pto4CL1-modified poplar cell walls	611:655	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	0	63	theme	Populus	116:122	arg1	tomentosa					124:132	perennial transgenic Populus tomentosa	95:132	perennial transgenic Populus tomentosa	95:132	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	8	64	theme	increased	1412:1420	arg1	density					1427:1433	slightly increased wood density	1403:1433	slightly increased wood density	1403:1433	Moreover, the increased lignin content caused significantly increased wood strength and slightly increased wood density.
31054469	12	65	theme	physical	1894:1901	arg1	properties					1918:1927	the physical and mechanical properties	1890:1927	the physical and mechanical properties of the wood	1890:1939	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	11	66	from	decrease	1678:1685	arg1	toughness					1730:1738	impact toughness	1723:1738	impact toughness in the low-lignin events	1723:1763	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	11	66	from	decrease	1678:1685	arg1	shrinkage					1697:1705	volume shrinkage	1690:1705	volume shrinkage	1690:1705	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	5	67	theme	control	868:874	arg1	plants					876:881	the control plants	864:881	the control plants	864:881	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	7	68	theme	cell	1304:1307	arg1	wall					1309:1312	the secondary cell wall	1290:1312	the secondary cell wall	1290:1312	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	11	69	theme	volume	1690:1695	arg1	shrinkage					1697:1705	volume shrinkage	1690:1705	volume shrinkage	1690:1705	We also found a significant decrease in volume shrinkage and increase in impact toughness in the low-lignin events.
31054469	0	70	theme	wall	56:59	arg1	components					61:70	cell wall components	51:70	cell wall components	51:70	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	1	71	theme	Cell	135:138	arg1	components					145:154	Cell wall components	135:154	Cell wall components	135:154	Cell wall components and structure impact the physical and mechanical properties of plants, thereby affecting wood applications.
31054469	6	72	theme	compensatory	1127:1138	arg1	variation					1140:1148	compensatory variation	1127:1148	compensatory variation	1127:1148	In contrast, the down-regulation of Pto4CL1 resulted in a reduction in lignin content to 27.39%, and the content of cellulose and hemi-cellulose showed compensatory variation.
31054469	7	73	theme	Raman	1151:1155	arg1	spectroscopy					1157:1168	Raman spectroscopy	1151:1168	Raman spectroscopy	1151:1168	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	2	74	from	biopolymer	292:301	arg1	wall					336:339	the wood cell wall	322:339	the wood cell wall	322:339	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	5	75	from	%	859:859	arg1	plants					876:881	the control plants	864:881	the control plants	864:881	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	4	76	dep	density	672:678	arg1	the					668:670	the	668:670	the	668:670	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	0	77	theme	perennial	95:103	arg1	tomentosa					124:132	perennial transgenic Populus tomentosa	95:132	perennial transgenic Populus tomentosa	95:132	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	1	78	theme	mechanical	194:203	arg1	properties					205:214	the physical and mechanical properties	177:214	the physical and mechanical properties of plants	177:224	Cell wall components and structure impact the physical and mechanical properties of plants, thereby affecting wood applications.
31054469	9	79	theme	significant	1493:1503	arg1	decrease					1505:1512	a significant decrease	1491:1512	a significant decrease in wood strength	1491:1529	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	2	80	theme	lignin	372:377	arg1	enzymes					392:398	certain lignin biosynthesis enzymes	364:398	certain lignin biosynthesis enzymes	364:398	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	4	81	from	poplar	541:546	arg1	impact					500:505	the impact	496:505	the impact of the regulation of Pto4CL1 from poplar on wood properties	496:565	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	4	81	from	poplar	541:546	arg1	regulation					514:523	the regulation	510:523	the regulation of Pto4CL1 from poplar	510:546	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	12	82	theme	cell	1854:1857	arg1	walls					1859:1863	plant cell walls	1848:1863	plant cell walls	1848:1863	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	4	83	theme	Pto4CL1	528:534	arg1	regulation					514:523	the regulation	510:523	the regulation of Pto4CL1 from poplar	510:546	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	3	84	theme	A	423:423	arg1	ligase					425:430	coenzyme A ligase	414:430	coenzyme A ligase(4CL)	414:435	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	84	theme	A	423:423	arg1	enzyme					473:478	an important lignin biosynthesis enzyme	440:478	an important lignin biosynthesis enzyme	440:478	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	84	theme	A	423:423	arg1	4-Coumarate					401:411	4-Coumarate	401:411	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.	401:479	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	84	theme	A	423:423	arg1	4CL					432:434	4CL	432:434	4CL	432:434	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	5	85	theme	hydrophilic	890:900	arg1	cellulose					926:934	cellulose	926:934	cellulose	926:934	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	5	85	theme	hydrophilic	890:900	arg1	hemi-cellulose					937:950	hemi-cellulose	937:950	hemi-cellulose	937:950	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	5	85	theme	hydrophilic	890:900	arg1	polysaccharides					902:916	hydrophilic polysaccharides	890:916	hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin	890:962	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	5	85	theme	hydrophilic	890:900	arg1	pectin					957:962	pectin	957:962	pectin	957:962	These results showed that the up-regulation of Pto4CL1 increased the lignin content to 46.65% from 33.11% in the control plants, while hydrophilic polysaccharides such as cellulose, hemi-cellulose, and pectin decreased.
31054469	0	86	theme	regulation	33:42	arg1	impact					15:20	the impact	11:20	the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa	11:132	Unraveling the impact of Pto4CL1 regulation on the cell wall components and wood properties of perennial transgenic Populus tomentosa.
31054469	12	87	theme	chemical	1824:1831	arg1	composition					1833:1843	the chemical composition	1820:1843	the chemical composition of plant cell walls	1820:1863	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	4	88	theme	regulation	514:523	arg1	impact					500:505	the impact	496:505	the impact of the regulation of Pto4CL1 from poplar on wood properties	496:565	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	8	89	theme	lignin	1339:1344	arg1	content					1346:1352	the increased lignin content	1325:1352	the increased lignin content	1325:1352	Moreover, the increased lignin content caused significantly increased wood strength and slightly increased wood density.
31054469	2	90	theme	cell	331:334	arg1	wall					336:339	the wood cell wall	322:339	the wood cell wall	322:339	Lignin is the most abundant biopolymer after cellulose in the wood cell wall and can be modified by certain lignin biosynthesis enzymes.
31054469	12	91	theme	Pto4CL1	1794:1800	arg1	regulation					1802:1811	Pto4CL1 regulation	1794:1811	Pto4CL1 regulation	1794:1811	These results indicate that Pto4CL1 regulation alters the chemical composition of plant cell walls and these changes affect the physical and mechanical properties of the wood.
31054469	9	92	theme	wood	1556:1559	arg1	density					1561:1567	wood density	1556:1567	wood density	1556:1567	In contrast, a reduction in lignin content resulted in a significant decrease in wood strength and a slight decrease in wood density.
31054469	7	93	from	deposition	1248:1257	arg1	wall					1309:1312	the secondary cell wall	1290:1312	the secondary cell wall	1290:1312	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	4	94	theme	trees	748:752	arg1	strength					681:688	strength	681:688	strength	681:688	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	4	94	theme	trees	748:752	arg1	shrinkage					698:706	volume shrinkage	691:706	volume shrinkage	691:706	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	4	94	theme	trees	748:752	arg1	density					672:678	density	672:678	density	672:678	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	4	94	theme	trees	748:752	arg1	toughness					720:728	impact toughness	713:728	impact toughness	713:728	To demonstrate the impact of the regulation of Pto4CL1 from poplar on wood properties, we analyzed the composition and anatomy of 5-year-old Pto4CL1-modified poplar cell walls, assessing the density, strength, volume shrinkage, and impact toughness of the transgenic trees.
31054469	3	95	theme	lignin	453:458	arg1	ligase					425:430	coenzyme A ligase	414:430	coenzyme A ligase(4CL)	414:435	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	95	theme	lignin	453:458	arg1	enzyme					473:478	an important lignin biosynthesis enzyme	440:478	an important lignin biosynthesis enzyme	440:478	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	3	95	theme	lignin	453:458	arg1	4-Coumarate					401:411	4-Coumarate	401:411	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.	401:479	4-Coumarate: coenzyme A ligase(4CL) is an important lignin biosynthesis enzyme.
31054469	7	96	from	concentration	1263:1275	arg1	wall					1309:1312	the secondary cell wall	1290:1312	the secondary cell wall	1290:1312	Raman spectroscopy showed that the change in lignin in the transgenic events was embodied in the deposition and concentration of lignin in the secondary cell wall.
31054469	10	97	theme	Pto4CL1-modified	1583:1598	arg1	trees					1600:1604	the Pto4CL1-modified trees	1579:1604	the Pto4CL1-modified trees	1579:1604	However, the Pto4CL1-modified trees had similar stiffness to the control group.
31054469	8	98	theme	increased	1375:1383	arg1	strength					1390:1397	significantly increased wood strength	1361:1397	significantly increased wood strength	1361:1397	Moreover, the increased lignin content caused significantly increased wood strength and slightly increased wood density.
31337704	5	0	theme	immune	1212:1217	arg1	glycoproteins					1233:1245	both immune and nonimmune glycoproteins	1207:1245	both immune and nonimmune glycoproteins	1207:1245	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	8	1	theme	MAGT1	1907:1911	arg1	deficiency					1913:1922	MAGT1 deficiency	1907:1922	MAGT1 deficiency	1907:1922	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	3	2	theme	EBV	548:550	arg1	susceptibility					552:565	EBV susceptibility	548:565	EBV susceptibility in XMEN	548:573	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	4	3	from	pathway	938:944	arg1	unknown					980:986	unknown	980:986	unknown	980:986	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	4	3	from	pathway	938:944	arg1	contributions					880:892	the exact contributions	870:892	the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis	870:968	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	8	4	from	defects	1868:1874	arg1	disease					1892:1898	an inherited disease	1879:1898	an inherited disease due to MAGT1 deficiency	1879:1922	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	2	5	contain	has	456:458	arg1	disease					443:449	a disease	441:449	a disease that has a broad range of clinical and immunological consequences	441:515	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	2	5	contain	has	456:458	arg2	range					468:472	a broad range	460:472	a broad range of clinical and immunological consequences	460:515	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	4	6	theme	glycosylation	838:850	arg1	complex					852:858	the N-linked glycosylation complex	825:858	the N-linked glycosylation complex	825:858	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	2	7	theme	MAGT1	332:336	arg1	gene					338:341	the MAGT1 gene	328:341	the MAGT1 gene	328:341	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	1	8	theme	magnesium	187:195	arg1	homeostasis					197:207	magnesium homeostasis	187:207	magnesium homeostasis in eukaryotes	187:221	Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches.
31337704	0	9	theme	immune-response	112:126	arg1	genes					128:132	immune-response genes	112:132	immune-response genes	112:132	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	5	10	theme	cell-killing	1074:1085	arg1	assays					1087:1092	natural killer cell-killing assays	1059:1092	natural killer cell-killing assays	1059:1092	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	4	11	theme	glycosylation	924:936	arg1	pathway					938:944	the glycosylation pathway	920:944	the glycosylation pathway	920:944	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	4	12	link	N-linked	829:836	arg1	complex					852:858	the N-linked glycosylation complex	825:858	the N-linked glycosylation complex	825:858	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	5	13	contain	have	1176:1179	arg2	deficiency					1193:1202	a selective deficiency	1181:1202	a selective deficiency in both immune and nonimmune glycoproteins	1181:1245	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	5	13	contain	have	1176:1179	arg1	humans					1144:1149	humans	1144:1149	humans lacking functional MAGT1	1144:1174	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	4	14	theme	New	709:711	arg1	evidence					713:720	New evidence	709:720	New evidence	709:720	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	1	15	from	homeostasis	197:207	arg1	eukaryotes					212:221	eukaryotes	212:221	eukaryotes	212:221	Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches.
31337704	7	16	theme	MAGT1-dependent	1625:1639	arg1	glycosylation					1641:1653	MAGT1-dependent glycosylation	1625:1653	MAGT1-dependent glycosylation	1625:1653	We observed that MAGT1-dependent glycosylation is sensitive to Mg2+ levels and that reduced Mg2+ impairs immune-cell function via the loss of specific glycoproteins.
31337704	0	17	from	expression	98:107	arg1	glycosylation					80:92	N-linked glycosylation	71:92	N-linked glycosylation	71:92	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	5	18	theme	natural	1059:1065	arg1	killer					1067:1072	natural killer	1059:1072	natural killer cell-killing assays	1059:1092	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	3	19	theme	natural-killer	632:645	arg1	protein					672:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	1	20	theme	Magnesium	135:143	arg1	transporter					145:155	Magnesium transporter 1	135:157	Magnesium transporter 1 (MAGT1)	135:165	Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches.
31337704	1	20	theme	Magnesium	135:143	arg1	MAGT1					160:164	MAGT1	160:164	MAGT1	160:164	Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches.
31337704	2	21	from	mutations	315:323	arg1	gene					338:341	the MAGT1 gene	328:341	the MAGT1 gene	328:341	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	2	22	theme	immunological	490:502	arg1	consequences					504:515	clinical and immunological consequences	477:515	clinical and immunological consequences	477:515	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	5	23	theme	immune-response	1318:1332	arg1	proteins					1334:1341	important immune-response proteins	1308:1341	important immune-response proteins	1308:1341	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	0	24	theme	selective	50:58	arg1	defects					60:66	selective defects	50:66	selective defects in N-linked glycosylation	50:92	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	6	25	theme	tissue	1577:1582	arg1	distribution					1584:1595	a different tissue distribution	1565:1595	a different tissue distribution in humans	1565:1605	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	2	26	theme	clinical	477:484	arg1	consequences					504:515	clinical and immunological consequences	477:515	clinical and immunological consequences	477:515	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	5	27	theme	several	1266:1272	arg1	defects					1297:1303	several critical glycosylation defects	1266:1303	several critical glycosylation defects	1266:1303	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	4	28	from	contributions	880:892	arg1	pathway					938:944	the glycosylation pathway	920:944	the glycosylation pathway	920:944	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	6	29	with	interchangeable	1453:1467	arg1	that					1474:1477	that	1474:1477	that	1474:1477	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	6	30	from	distribution	1584:1595	arg1	humans					1600:1605	humans	1600:1605	humans	1600:1605	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	5	31	gly	glycoproteins	1233:1245	arg1	glycoproteins					1233:1245	both immune and nonimmune glycoproteins	1207:1245	both immune and nonimmune glycoproteins	1207:1245	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	5	32	theme	glycosylation	1283:1295	arg1	defects					1297:1303	several critical glycosylation defects	1266:1303	several critical glycosylation defects	1266:1303	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	5	33	theme	RNA-Seq	1099:1105	arg1	experiments					1107:1117	RNA-Seq experiments	1099:1117	RNA-Seq experiments	1099:1117	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	2	34	theme	loss-of-function	298:313	arg1	mutations					315:323	loss-of-function mutations	298:323	loss-of-function mutations in the MAGT1 gene	298:341	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	7	35	theme	glycoproteins	1759:1771	arg1	loss					1742:1745	the loss	1738:1745	the loss of specific glycoproteins	1738:1771	We observed that MAGT1-dependent glycosylation is sensitive to Mg2+ levels and that reduced Mg2+ impairs immune-cell function via the loss of specific glycoproteins.
31337704	5	36	theme	nonimmune	1223:1231	arg1	glycoproteins					1233:1245	both immune and nonimmune glycoproteins	1207:1245	both immune and nonimmune glycoproteins	1207:1245	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	0	37	theme	Magnesium	0:8	arg1	deficiency					32:41	Magnesium transporter 1 (MAGT1) deficiency	0:41	Magnesium transporter 1 (MAGT1) deficiency	0:41	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	7	38	theme	reduced	1692:1698	arg1	Mg2+					1700:1703	reduced Mg2+	1692:1703	reduced Mg2+	1692:1703	We observed that MAGT1-dependent glycosylation is sensitive to Mg2+ levels and that reduced Mg2+ impairs immune-cell function via the loss of specific glycoproteins.
31337704	3	39	theme	D	662:662	arg1	protein					672:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	0	40	theme	MAGT1	25:29	arg1	deficiency					32:41	Magnesium transporter 1 (MAGT1) deficiency	0:41	Magnesium transporter 1 (MAGT1) deficiency	0:41	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	0	41	link	N-linked	71:78	arg1	glycosylation					80:92	N-linked glycosylation	71:92	N-linked glycosylation	71:92	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	5	42	theme	cell	1047:1050	arg1	lines					1052:1056	CRISPR/Cas9-KO cell lines	1032:1056	CRISPR/Cas9-KO cell lines	1032:1056	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	3	43	theme	protein	672:678	arg1	expression					604:613	defective expression	594:613	defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein	594:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	3	43	theme	protein	672:678	arg1	transport					698:706	abnormal Mg2+ transport	684:706	abnormal Mg2+ transport	684:706	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	4	44	theme	OST3/OST6	776:784	arg1	proteins					786:793	the yeast OST3/OST6 proteins	766:793	the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown	766:986	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	2	45	theme	X-linked	349:356	arg1	deficiency					368:377	X-linked magnesium deficiency	349:377	X-linked magnesium deficiency	349:377	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	8	46	theme	gene	1836:1839	arg1	expression					1841:1850	gene expression	1836:1850	gene expression	1836:1850	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	5	47	theme	MS-based	995:1002	arg1	glycoproteomics					1004:1018	MS-based glycoproteomics	995:1018	MS-based glycoproteomics	995:1018	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	3	48	theme	NKG2D	665:669	arg1	protein					672:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	6	49	theme	tumor-suppressor	1502:1517	arg1	TUSC3					1532:1536	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	2	50	theme	Epstein-Barr	384:395	arg1	EBV					404:406	EBV	404:406	EBV	404:406	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	2	50	theme	Epstein-Barr	384:395	arg1	virus					397:401	Epstein-Barr virus	384:401	Epstein-Barr virus (EBV) infection	384:417	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	6	51	theme	paralog	1486:1492	arg1	TUSC3					1532:1536	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	1	52	theme	evolutionary	264:275	arg1	branches					277:284	different evolutionary branches	254:284	different evolutionary branches	254:284	Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches.
31337704	4	53	theme	complex	852:858	arg1	part					817:820	an integral part	805:820	an integral part of the N-linked glycosylation complex	805:858	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	3	54	theme	abnormal	684:691	arg1	transport					698:706	abnormal Mg2+ transport	684:706	abnormal Mg2+ transport	684:706	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	5	55	from	deficiency	1193:1202	arg1	glycoproteins					1233:1245	both immune and nonimmune glycoproteins	1207:1245	both immune and nonimmune glycoproteins	1207:1245	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	8	56	from	defects	1799:1805	arg1	glycosylation					1818:1830	protein glycosylation	1810:1830	protein glycosylation	1810:1830	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	8	56	from	defects	1799:1805	arg1	expression					1841:1850	gene expression	1836:1850	gene expression	1836:1850	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	7	57	theme	Mg2+	1671:1674	arg1	levels					1676:1681	Mg2+ levels	1671:1681	Mg2+ levels	1671:1681	We observed that MAGT1-dependent glycosylation is sensitive to Mg2+ levels and that reduced Mg2+ impairs immune-cell function via the loss of specific glycoproteins.
31337704	4	58	theme	N-linked	829:836	arg1	complex					852:858	the N-linked glycosylation complex	825:858	the N-linked glycosylation complex	825:858	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	0	59	theme	genes	128:132	arg1	expression					98:107	expression	98:107	expression of immune-response genes	98:132	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	0	59	theme	genes	128:132	arg1	defects					60:66	selective defects	50:66	selective defects in N-linked glycosylation	50:92	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	4	60	theme	perturbations	903:915	arg1	unknown					980:986	unknown	980:986	unknown	980:986	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	4	60	theme	perturbations	903:915	arg1	contributions					880:892	the exact contributions	870:892	the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis	870:968	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	3	61	theme	defective	594:602	arg1	expression					604:613	defective expression	594:613	defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein	594:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	0	62	from	defects	60:66	arg1	glycosylation					80:92	N-linked glycosylation	71:92	N-linked glycosylation	71:92	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	4	63	from	perturbations	903:915	arg1	pathway					938:944	the glycosylation pathway	920:944	the glycosylation pathway	920:944	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	4	64	theme	exact	874:878	arg1	unknown					980:986	unknown	980:986	unknown	980:986	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	4	64	theme	exact	874:878	arg1	contributions					880:892	the exact contributions	870:892	the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis	870:968	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	3	65	from	susceptibility	552:565	arg1	XMEN					570:573	XMEN	570:573	XMEN	570:573	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	3	66	theme	antiviral	622:630	arg1	protein					672:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	5	67	theme	important	1308:1316	arg1	proteins					1334:1341	important immune-response proteins	1308:1341	important immune-response proteins	1308:1341	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	5	68	theme	killer	1067:1072	arg1	assays					1087:1092	natural killer cell-killing assays	1059:1092	natural killer cell-killing assays	1059:1092	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	8	69	theme	protein	1810:1816	arg1	glycosylation					1818:1830	protein glycosylation	1810:1830	protein glycosylation	1810:1830	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	0	70	theme	N-linked	71:78	arg1	glycosylation					80:92	N-linked glycosylation	71:92	N-linked glycosylation	71:92	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	6	71	theme	different	1567:1575	arg1	distribution					1584:1595	a different tissue distribution	1565:1595	a different tissue distribution in humans	1565:1605	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	7	72	theme	specific	1750:1757	arg1	glycoproteins					1759:1771	specific glycoproteins	1750:1771	specific glycoproteins	1750:1771	We observed that MAGT1-dependent glycosylation is sensitive to Mg2+ levels and that reduced Mg2+ impairs immune-cell function via the loss of specific glycoproteins.
31337704	5	73	theme	critical	1274:1281	arg1	defects					1297:1303	several critical glycosylation defects	1266:1303	several critical glycosylation defects	1266:1303	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	6	74	contain	has	1561:1563	arg1	protein					1553:1559	each protein	1548:1559	each protein	1548:1559	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	6	74	contain	has	1561:1563	arg2	distribution					1584:1595	a different tissue distribution	1565:1595	a different tissue distribution in humans	1565:1605	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	4	75	theme	human	749:753	arg1	homolog					755:761	the human homolog	745:761	the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown	745:986	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	4	75	theme	human	749:753	arg1	MAGT1					736:740	MAGT1	736:740	MAGT1	736:740	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	8	76	theme	immune	1861:1866	arg1	defects					1868:1874	immune defects	1861:1874	immune defects in an inherited disease due to MAGT1 deficiency	1861:1922	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	2	77	theme	consequences	504:515	arg1	range					468:472	a broad range	460:472	a broad range of clinical and immunological consequences	460:515	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	5	78	theme	genes	1368:1372	arg1	expression					1354:1363	the expression	1350:1363	the expression of genes involved in immunity, particularly CD28	1350:1412	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	0	79	theme	transporter	10:20	arg1	deficiency					32:41	Magnesium transporter 1 (MAGT1) deficiency	0:41	Magnesium transporter 1 (MAGT1) deficiency	0:41	Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes.
31337704	7	80	theme	immune-cell	1713:1723	arg1	function					1725:1732	immune-cell function	1713:1732	immune-cell function	1713:1732	We observed that MAGT1-dependent glycosylation is sensitive to Mg2+ levels and that reduced Mg2+ impairs immune-cell function via the loss of specific glycoproteins.
31337704	5	81	theme	selective	1183:1191	arg1	deficiency					1193:1202	a selective deficiency	1181:1202	a selective deficiency in both immune and nonimmune glycoproteins	1181:1245	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	8	82	theme	inherited	1882:1890	arg1	disease					1892:1898	an inherited disease	1879:1898	an inherited disease due to MAGT1 deficiency	1879:1922	Our findings reveal that defects in protein glycosylation and gene expression underlie immune defects in an inherited disease due to MAGT1 deficiency.
31337704	3	83	theme	member	655:660	arg1	protein					672:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	2	84	theme	broad	462:466	arg1	range					468:472	a broad range	460:472	a broad range of clinical and immunological consequences	460:515	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	3	85	theme	group	647:651	arg1	protein					672:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	the antiviral natural-killer group 2 member D (NKG2D) protein	618:678	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	4	86	theme	disease	949:955	arg1	pathogenesis					957:968	disease pathogenesis	949:968	disease pathogenesis	949:968	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	6	87	theme	MAGT1	1428:1432	arg1	function					1434:1441	MAGT1 function	1428:1441	MAGT1 function	1428:1441	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	5	88	theme	functional	1159:1168	arg1	MAGT1					1170:1174	functional MAGT1	1159:1174	functional MAGT1	1159:1174	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	5	89	theme	CRISPR/Cas9-KO	1032:1045	arg1	lines					1052:1056	CRISPR/Cas9-KO cell lines	1032:1056	CRISPR/Cas9-KO cell lines	1032:1056	Using MS-based glycoproteomics, along with CRISPR/Cas9-KO cell lines, natural killer cell-killing assays, and RNA-Seq experiments, we now demonstrate that humans lacking functional MAGT1 have a selective deficiency in both immune and nonimmune glycoproteins, and we identified several critical glycosylation defects in important immune-response proteins and in the expression of genes involved in immunity, particularly CD28.
31337704	2	90	link	X-linked	349:356	arg1	deficiency					368:377	X-linked magnesium deficiency	349:377	X-linked magnesium deficiency	349:377	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	4	91	theme	integral	808:815	arg1	part					817:820	an integral part	805:820	an integral part of the N-linked glycosylation complex	805:858	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	2	92	theme	magnesium	358:366	arg1	deficiency					368:377	X-linked magnesium deficiency	349:377	X-linked magnesium deficiency	349:377	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	4	93	theme	yeast	770:774	arg1	proteins					786:793	the yeast OST3/OST6 proteins	766:793	the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown	766:986	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	6	94	theme	candidate	1519:1527	arg1	TUSC3					1532:1536	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	7	95	gly	glycoproteins	1759:1771	arg1	glycoproteins					1759:1771	specific glycoproteins	1750:1771	specific glycoproteins	1750:1771	We observed that MAGT1-dependent glycosylation is sensitive to Mg2+ levels and that reduced Mg2+ impairs immune-cell function via the loss of specific glycoproteins.
31337704	3	96	theme	Mg2+	693:696	arg1	transport					698:706	abnormal Mg2+ transport	684:706	abnormal Mg2+ transport	684:706	We have previously shown that EBV susceptibility in XMEN is associated with defective expression of the antiviral natural-killer group 2 member D (NKG2D) protein and abnormal Mg2+ transport.
31337704	4	97	theme	proteins	786:793	arg1	homolog					755:761	the human homolog	745:761	the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown	745:986	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	4	97	theme	proteins	786:793	arg1	MAGT1					736:740	MAGT1	736:740	MAGT1	736:740	New evidence suggests that MAGT1 is the human homolog of the yeast OST3/OST6 proteins that form an integral part of the N-linked glycosylation complex, although the exact contributions of these perturbations in the glycosylation pathway to disease pathogenesis are still unknown.
31337704	2	98	theme	virus	397:401	arg1	infection					409:417	Epstein-Barr virus (EBV) infection	384:417	Epstein-Barr virus (EBV) infection	384:417	In humans, loss-of-function mutations in the MAGT1 gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasia (XMEN), a disease that has a broad range of clinical and immunological consequences.
31337704	6	99	theme	protein	1494:1500	arg1	TUSC3					1532:1536	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	the paralog protein tumor-suppressor candidate 3 (TUSC3)	1482:1537	We show that MAGT1 function is partly interchangeable with that of the paralog protein tumor-suppressor candidate 3 (TUSC3) but that each protein has a different tissue distribution in humans.
31337704	1	100	theme	different	254:262	arg1	branches					277:284	different evolutionary branches	254:284	different evolutionary branches	254:284	Magnesium transporter 1 (MAGT1) critically mediates magnesium homeostasis in eukaryotes and is highly-conserved across different evolutionary branches.
29746846	8	0	from	Proteins	1246:1253	arg1	endothelial					1258:1268	endothelial	1258:1268	endothelial	1258:1268	Proteins in endothelial and trophoblast cells were the main target for O-GlcNAc.
29746846	8	0	from	Proteins	1246:1253	arg1	cells					1286:1290	trophoblast cells	1274:1290	trophoblast cells	1274:1290	Proteins in endothelial and trophoblast cells were the main target for O-GlcNAc.
29746846	9	1	from	group	1486:1490	arg1	placentas					1446:1454	placentas	1446:1454	placentas from the severe hyperglycemic group	1446:1490	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	11	2	theme	morphometric	1740:1751	arg1	alterations					1753:1763	morphometric alterations	1740:1763	morphometric alterations	1740:1763	Additionally, morphometric alterations, occurring simultaneously with increased O-GlcNAc accumulation in the placental tissue may contribute to placental dysfunction during hyperglycemia.
29746846	9	3	theme	severe	1465:1470	arg1	group					1486:1490	the severe hyperglycemic group	1461:1490	the severe hyperglycemic group	1461:1490	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	0	4	link	O-linked	0:7	arg1	deposition					30:39	O-linked N-acetyl-glucosamine deposition	0:39	O-linked N-acetyl-glucosamine deposition in placental proteins	0:61	O-linked N-acetyl-glucosamine deposition in placental proteins varies according to maternal glycemic levels.
29746846	10	5	theme	Placental	1614:1622	arg1	overexpression					1633:1646	SIGNIFICANCE Placental O-GlcNAc overexpression	1601:1646	SIGNIFICANCE Placental O-GlcNAc overexpression	1601:1646	SIGNIFICANCE Placental O-GlcNAc overexpression may contribute to placental dysfunction, as indicated by the placental index.
29746846	7	6	theme	increased	1144:1152	arg1	levels					1163:1168	increased O-GlcNAc levels	1144:1168	increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats	1144:1243	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
29746846	0	7	theme	O-linked	0:7	arg1	deposition					30:39	O-linked N-acetyl-glucosamine deposition	0:39	O-linked N-acetyl-glucosamine deposition in placental proteins	0:61	O-linked N-acetyl-glucosamine deposition in placental proteins varies according to maternal glycemic levels.
29746846	1	8	theme	placental	214:222	arg1	dysfunction					224:234	placental dysfunction	214:234	placental dysfunction	214:234	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	4	9	theme	pregnancy	673:681	arg1	21 days					662:668	21 days	662:668	21 days of pregnancy	662:681	At 21 days of pregnancy, placental tissue was collected and processed for morphometry and immunohistochemistry analyses, or properly stored at -80 °C for protein quantification by western blot.
29746846	10	10	theme	placental	1666:1674	arg1	dysfunction					1676:1686	placental dysfunction	1666:1686	placental dysfunction	1666:1686	SIGNIFICANCE Placental O-GlcNAc overexpression may contribute to placental dysfunction, as indicated by the placental index.
29746846	2	11	theme	O-GlcNAc	348:355	arg1	distribution					357:368	the O-GlcNAc distribution	344:368	the O-GlcNAc distribution	344:368	Our aim was to determine how O-GlcNAc levels are affected by hyperglycemia and the O-GlcNAc distribution in different placental regions.
29746846	3	12	theme	oral	585:588	arg1	test					608:611	oral glucose tolerance test	585:611	oral glucose tolerance test	585:611	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	5	13	theme	KEY	853:855	arg1	FINDINGS					857:864	KEY FINDINGS	853:864	KEY FINDINGS Placental index	853:880	KEY FINDINGS Placental index was increased only in severe hyperglycemic rats.
29746846	6	14	theme	decreased	990:998	arg1	region					1010:1015	decreased labyrinth region	990:1015	decreased labyrinth region	990:1015	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	5	15	theme	Placental	866:874	arg1	index					876:880	KEY FINDINGS Placental index	853:880	KEY FINDINGS Placental index	853:880	KEY FINDINGS Placental index was increased only in severe hyperglycemic rats.
29746846	9	16	theme	hyperglycemic	1533:1545	arg1	group					1547:1551	the mild hyperglycemic group	1524:1551	the mild hyperglycemic group	1524:1551	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	6	17	theme	increased	960:968	arg1	zone					981:984	increased junctional zone	960:984	increased junctional zone	960:984	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	2	18	theme	O-GlcNAc	294:301	arg1	levels					303:308	O-GlcNAc levels	294:308	O-GlcNAc levels	294:308	Our aim was to determine how O-GlcNAc levels are affected by hyperglycemia and the O-GlcNAc distribution in different placental regions.
29746846	4	19	dep	morphometry	733:743	arg1	analyses					770:777	analyses	770:777	analyses	770:777	At 21 days of pregnancy, placental tissue was collected and processed for morphometry and immunohistochemistry analyses, or properly stored at -80 °C for protein quantification by western blot.
29746846	2	20	from	hyperglycemia	326:338	arg1	regions					393:399	different placental regions	373:399	different placental regions	373:399	Our aim was to determine how O-GlcNAc levels are affected by hyperglycemia and the O-GlcNAc distribution in different placental regions.
29746846	4	21	theme	placental	684:692	arg1	tissue					694:699	placental tissue	684:699	placental tissue	684:699	At 21 days of pregnancy, placental tissue was collected and processed for morphometry and immunohistochemistry analyses, or properly stored at -80 °C for protein quantification by western blot.
29746846	5	22	theme	severe	904:909	arg1	rats					925:928	severe hyperglycemic rats	904:928	severe hyperglycemic rats	904:928	KEY FINDINGS Placental index was increased only in severe hyperglycemic rats.
29746846	6	23	theme	severe	1051:1056	arg1	group					1072:1076	the severe hyperglycemic group	1047:1076	the severe hyperglycemic group	1047:1076	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	11	24	from	accumulation	1815:1826	arg1	tissue					1845:1850	the placental tissue	1831:1850	the placental tissue	1831:1850	Additionally, morphometric alterations, occurring simultaneously with increased O-GlcNAc accumulation in the placental tissue may contribute to placental dysfunction during hyperglycemia.
29746846	0	25	from	deposition	30:39	arg1	proteins					54:61	placental proteins	44:61	placental proteins	44:61	O-linked N-acetyl-glucosamine deposition in placental proteins varies according to maternal glycemic levels.
29746846	11	26	theme	placental	1870:1878	arg1	dysfunction					1880:1890	placental dysfunction	1870:1890	placental dysfunction	1870:1890	Additionally, morphometric alterations, occurring simultaneously with increased O-GlcNAc accumulation in the placental tissue may contribute to placental dysfunction during hyperglycemia.
29746846	0	27	theme	glycemic	92:99	arg1	levels					101:106	maternal glycemic levels	83:106	maternal glycemic levels	83:106	O-linked N-acetyl-glucosamine deposition in placental proteins varies according to maternal glycemic levels.
29746846	9	28	theme	respective	1574:1583	arg1	groups					1593:1598	their respective control groups	1568:1598	their respective control groups	1568:1598	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	2	29	from	distribution	357:368	arg1	regions					393:399	different placental regions	373:399	different placental regions	373:399	Our aim was to determine how O-GlcNAc levels are affected by hyperglycemia and the O-GlcNAc distribution in different placental regions.
29746846	9	30	theme	transferase	1358:1368	arg1	expression					1376:1385	O-GlcNAc transferase (OGT) expression	1349:1385	O-GlcNAc transferase (OGT) expression	1349:1385	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	10	31	theme	placental	1709:1717	arg1	index					1719:1723	the placental index	1705:1723	the placental index	1705:1723	SIGNIFICANCE Placental O-GlcNAc overexpression may contribute to placental dysfunction, as indicated by the placental index.
29746846	7	32	theme	hyperglycemic	1226:1238	arg1	rats					1240:1243	mild hyperglycemic rats	1221:1243	mild hyperglycemic rats	1221:1243	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
29746846	1	33	theme	AIMS	109:112	arg1	Hyperglycemia					114:126	AIMS Hyperglycemia	109:126	AIMS Hyperglycemia	109:126	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	3	34	theme	Wistar	422:427	arg1	rats					429:432	Female Wistar rats	415:432	Female Wistar rats	415:432	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	3	35	dep	normoglycemia	624:636	arg1	<120 mg/dL					639:648	<120 mg/dL	639:648	<120 mg/dL; n = 6	639:655	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	4	36	dep	collected	705:713	arg1	stored					792:797	stored	792:797	stored at -80 °C for protein quantification by western blot	792:850	At 21 days of pregnancy, placental tissue was collected and processed for morphometry and immunohistochemistry analyses, or properly stored at -80 °C for protein quantification by western blot.
29746846	3	37	theme	following	456:464	arg1	groups					466:471	the following groups	452:471	the following groups	452:471	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	0	38	theme	placental	44:52	arg1	proteins					54:61	placental proteins	44:61	placental proteins	44:61	O-linked N-acetyl-glucosamine deposition in placental proteins varies according to maternal glycemic levels.
29746846	9	39	theme	O-GlcNAcase	1402:1412	arg1	expression					1420:1429	O-GlcNAcase (OGA) expression	1402:1429	O-GlcNAcase (OGA) expression	1402:1429	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	7	40	from	levels	1163:1168	arg1	group					1191:1195	the hyperglycemic group	1173:1195	the hyperglycemic group compared to control and mild hyperglycemic rats	1173:1243	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
29746846	1	41	link	O-linked	157:164	arg1	O-GlcNAc					188:195	O-GlcNAc	188:195	O-GlcNAc	188:195	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	1	41	link	O-linked	157:164	arg1	N-acetyl-glucosamine					166:185	O-linked N-acetyl-glucosamine	157:185	O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment	157:262	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	9	42	theme	OGA	1415:1417	arg1	expression					1420:1429	O-GlcNAcase (OGA) expression	1402:1429	O-GlcNAcase (OGA) expression	1402:1429	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	3	43	dep	METHODS	407:413	arg1	divided					439:445	divided	439:445	were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6)	434:656	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	2	44	theme	different	373:381	arg1	regions					393:399	different placental regions	373:399	different placental regions	373:399	Our aim was to determine how O-GlcNAc levels are affected by hyperglycemia and the O-GlcNAc distribution in different placental regions.
29746846	9	45	from	changes	1338:1344	arg1	expression					1376:1385	O-GlcNAc transferase (OGT) expression	1349:1385	O-GlcNAc transferase (OGT) expression	1349:1385	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	10	46	theme	SIGNIFICANCE	1601:1612	arg1	overexpression					1633:1646	SIGNIFICANCE Placental O-GlcNAc overexpression	1601:1646	SIGNIFICANCE Placental O-GlcNAc overexpression	1601:1646	SIGNIFICANCE Placental O-GlcNAc overexpression may contribute to placental dysfunction, as indicated by the placental index.
29746846	11	47	theme	O-GlcNAc	1806:1813	arg1	accumulation					1815:1826	increased O-GlcNAc accumulation	1796:1826	increased O-GlcNAc accumulation in the placental tissue	1796:1850	Additionally, morphometric alterations, occurring simultaneously with increased O-GlcNAc accumulation in the placental tissue may contribute to placental dysfunction during hyperglycemia.
29746846	4	48	theme	protein	813:819	arg1	quantification					821:834	protein quantification	813:834	protein quantification	813:834	At 21 days of pregnancy, placental tissue was collected and processed for morphometry and immunohistochemistry analyses, or properly stored at -80 °C for protein quantification by western blot.
29746846	6	49	theme	Morphometric	931:942	arg1	analysis					944:951	Morphometric analysis	931:951	Morphometric analysis	931:951	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	7	50	theme	O-GlcNAc	1154:1161	arg1	levels					1163:1168	increased O-GlcNAc levels	1144:1168	increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats	1144:1243	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
29746846	3	51	theme	time	566:569	arg1	points					571:576	two time points	562:576	two time points during oral glucose tolerance test	562:611	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	10	52	theme	O-GlcNAc	1624:1631	arg1	overexpression					1633:1646	SIGNIFICANCE Placental O-GlcNAc overexpression	1601:1646	SIGNIFICANCE Placental O-GlcNAc overexpression	1601:1646	SIGNIFICANCE Placental O-GlcNAc overexpression may contribute to placental dysfunction, as indicated by the placental index.
29746846	9	53	theme	hyperglycemic	1472:1484	arg1	group					1486:1490	the severe hyperglycemic group	1461:1490	the severe hyperglycemic group	1461:1490	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	9	54	from	group	1547:1551	arg1	placentas					1509:1517	placentas	1509:1517	placentas from the mild hyperglycemic group	1509:1551	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	3	55	theme	glucose	590:596	arg1	test					608:611	oral glucose tolerance test	585:611	oral glucose tolerance test	585:611	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	8	56	theme	main	1301:1304	arg1	Proteins					1246:1253	Proteins	1246:1253	Proteins in endothelial and trophoblast cells	1246:1290	Proteins in endothelial and trophoblast cells were the main target for O-GlcNAc.
29746846	8	56	theme	main	1301:1304	arg1	target					1306:1311	the main target	1297:1311	the main target for O-GlcNAc	1297:1324	Proteins in endothelial and trophoblast cells were the main target for O-GlcNAc.
29746846	1	57	theme	fetal	240:244	arg1	impairment					253:262	fetal growth impairment	240:262	fetal growth impairment	240:262	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	3	58	theme	tolerance	598:606	arg1	test					608:611	oral glucose tolerance test	585:611	oral glucose tolerance test	585:611	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	6	59	theme	labyrinth	1000:1008	arg1	region					1010:1015	decreased labyrinth region	990:1015	decreased labyrinth region	990:1015	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	5	60	theme	FINDINGS	857:864	arg1	index					876:880	KEY FINDINGS Placental index	853:880	KEY FINDINGS Placental index	853:880	KEY FINDINGS Placental index was increased only in severe hyperglycemic rats.
29746846	9	61	theme	mild	1528:1531	arg1	group					1547:1551	the mild hyperglycemic group	1524:1551	the mild hyperglycemic group	1524:1551	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	8	62	theme	trophoblast	1274:1284	arg1	cells					1286:1290	trophoblast cells	1274:1290	trophoblast cells	1274:1290	Proteins in endothelial and trophoblast cells were the main target for O-GlcNAc.
29746846	6	63	theme	junctional	970:979	arg1	zone					981:984	increased junctional zone	960:984	increased junctional zone	960:984	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	1	64	theme	O-linked	157:164	arg1	O-GlcNAc					188:195	O-GlcNAc	188:195	O-GlcNAc	188:195	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	1	64	theme	O-linked	157:164	arg1	N-acetyl-glucosamine					166:185	O-linked N-acetyl-glucosamine	157:185	O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment	157:262	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	0	65	theme	maternal	83:90	arg1	levels					101:106	maternal glycemic levels	83:106	maternal glycemic levels	83:106	O-linked N-acetyl-glucosamine deposition in placental proteins varies according to maternal glycemic levels.
29746846	6	66	theme	hyperglycemic	1058:1070	arg1	group					1072:1076	the severe hyperglycemic group	1047:1076	the severe hyperglycemic group	1047:1076	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	11	67	theme	placental	1835:1843	arg1	tissue					1845:1850	the placental tissue	1831:1850	the placental tissue	1831:1850	Additionally, morphometric alterations, occurring simultaneously with increased O-GlcNAc accumulation in the placental tissue may contribute to placental dysfunction during hyperglycemia.
29746846	5	68	theme	hyperglycemic	911:923	arg1	rats					925:928	severe hyperglycemic rats	904:928	severe hyperglycemic rats	904:928	KEY FINDINGS Placental index was increased only in severe hyperglycemic rats.
29746846	9	69	theme	O-GlcNAc	1349:1356	arg1	OGT					1371:1373	OGT	1371:1373	OGT	1371:1373	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	9	69	theme	O-GlcNAc	1349:1356	arg1	transferase					1358:1368	O-GlcNAc transferase	1349:1368	O-GlcNAc transferase (OGT) expression	1349:1385	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	9	70	theme	control	1585:1591	arg1	groups					1593:1598	their respective control groups	1568:1598	their respective control groups	1568:1598	Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.
29746846	3	71	theme	Female	415:420	arg1	rats					429:432	Female Wistar rats	415:432	Female Wistar rats	415:432	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	6	72	from	group	1072:1076	arg1	placentas					1020:1028	placentas	1020:1028	placentas exclusively from the severe hyperglycemic group	1020:1076	Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group.
29746846	1	73	theme	growth	246:251	arg1	impairment					253:262	fetal growth impairment	240:262	fetal growth impairment	240:262	AIMS Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment.
29746846	3	74	theme	MAIN	402:405	arg1	METHODS					407:413	MAIN METHODS	402:413	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).	402:657	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	0	75	theme	N-acetyl-glucosamine	9:28	arg1	deposition					30:39	O-linked N-acetyl-glucosamine deposition	0:39	O-linked N-acetyl-glucosamine deposition in placental proteins	0:61	O-linked N-acetyl-glucosamine deposition in placental proteins varies according to maternal glycemic levels.
29746846	3	76	dep	>140 mg/dL	536:545	arg1	n = 7					614:618	n = 7	614:618	n = 7	614:618	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	3	77	theme	severe	474:479	arg1	hyperglycemia					481:493	severe hyperglycemia	474:493	severe hyperglycemia (>300 mg/dL; n = 5)	474:513	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	7	78	located	detected	1114:1121	arg2	Proteins					1079:1086	Proteins	1079:1086	Proteins targeted by O-GlcNAc	1079:1107	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
29746846	7	78	located	detected	1114:1121	arg1	regions					1130:1136	all regions	1126:1136	all regions	1126:1136	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
29746846	7	79	theme	hyperglycemic	1177:1189	arg1	group					1191:1195	the hyperglycemic group	1173:1195	the hyperglycemic group compared to control and mild hyperglycemic rats	1173:1243	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
29746846	3	80	dep	hyperglycemia	481:493	arg1	>300 mg/dL					496:505	>300 mg/dL	496:505	>300 mg/dL; n = 5	496:512	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	4	81	theme	western	839:845	arg1	blot					847:850	western blot	839:850	western blot	839:850	At 21 days of pregnancy, placental tissue was collected and processed for morphometry and immunohistochemistry analyses, or properly stored at -80 °C for protein quantification by western blot.
29746846	2	82	theme	placental	383:391	arg1	regions					393:399	different placental regions	373:399	different placental regions	373:399	Our aim was to determine how O-GlcNAc levels are affected by hyperglycemia and the O-GlcNAc distribution in different placental regions.
29746846	3	83	dep	>300 mg/dL	496:505	arg1	n = 5					508:512	n = 5	508:512	>300 mg/dL; n = 5	496:512	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	11	84	theme	increased	1796:1804	arg1	accumulation					1815:1826	increased O-GlcNAc accumulation	1796:1826	increased O-GlcNAc accumulation in the placental tissue	1796:1850	Additionally, morphometric alterations, occurring simultaneously with increased O-GlcNAc accumulation in the placental tissue may contribute to placental dysfunction during hyperglycemia.
29746846	3	85	theme	mild	516:519	arg1	hyperglycemia					521:533	mild hyperglycemia	516:533	mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7)	516:619	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	3	85	theme	mild	516:519	arg1	>140 mg/dL					536:545	>140 mg/dL	536:545	>140 mg/dL	536:545	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	3	86	dep	<120 mg/dL	639:648	arg1	n = 6					651:655	n = 6	651:655	<120 mg/dL; n = 6	639:655	MAIN METHODS Female Wistar rats were divided into the following groups: severe hyperglycemia (>300 mg/dL; n = 5); mild hyperglycemia (>140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (<120 mg/dL; n = 6).
29746846	7	87	theme	mild	1221:1224	arg1	rats					1240:1243	mild hyperglycemic rats	1221:1243	mild hyperglycemic rats	1221:1243	Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats.
30369266	2	0	theme	antibodies	575:584	arg1	level					557:561	the level	553:561	the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992)	553:622	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	7	1	located	observed	1571:1578	arg1	group					1587:1591	the group	1583:1591	the group of patients under corticosteroid treatment	1583:1634	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	7	1	located	observed	1571:1578	arg1	patients					1596:1603	patients	1596:1603	patients under corticosteroid treatment	1596:1634	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	7	1	located	observed	1571:1578	arg2	increase					1529:1536	Significant increase	1517:1536	Significant increase	1517:1536	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	5	2	theme	lectin	1156:1161	arg1	AAL					1163:1165	core α1,6-fucose specific lectin AAL	1130:1165	core α1,6-fucose specific lectin AAL	1130:1165	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	7	3	theme	SNA	1685:1687	arg1	binding					1696:1702	sialyl-specific PSqL and SNA lectin binding	1660:1702	binding	1696:1702	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	4	4	theme	clinical	1009:1016	arg1	condition					1018:1026	a particularly interesting clinical condition	982:1026	a particularly interesting clinical condition	982:1026	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	11	5	theme	subsequent	2232:2241	arg1	exposure					2243:2250	subsequent exposure	2232:2250	subsequent exposure of hidden glycoepitops	2232:2273	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	5	6	from	complexes	1198:1206	arg1	groups					1216:1221	five groups	1211:1221	five groups of MS patients	1211:1236	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	6	from	complexes	1198:1206	arg1	patients					1229:1236	MS patients	1226:1236	MS patients	1226:1236	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	12	7	theme	immune	2387:2392	arg1	complexes					2394:2402	immune complexes	2387:2402	immune complexes leading to exposure of internal glycoepitops	2387:2447	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	8	8	theme	acid	1776:1779	arg1	residues					1781:1788	sialic acid residues	1769:1788	sialic acid residues	1769:1788	Subsequent analysis demonstrated that sialic acid residues were exposed on free IgG and on circulating IgG-IgM immune complexes.
30369266	11	9	theme	generated	2130:2138	arg1	NETs					2140:2143	in vitro generated NETs	2121:2143	in vitro generated NETs	2121:2143	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	10	10	theme	low	2026:2028	arg1	activity					2050:2057	low neutrophil elastase activity	2026:2057	low neutrophil elastase activity	2026:2057	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	4	11	theme	detection	876:884	arg1	markers					886:892	no reliable detection markers	864:892	no reliable detection markers	864:892	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	12	12	theme	glycoepitops	2436:2447	arg1	exposure					2415:2422	exposure	2415:2422	exposure of internal glycoepitops	2415:2447	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	10	13	theme	IFN	1995:1997	arg1	therapy					1999:2005	IFN therapy	1995:2005	IFN therapy	1995:2005	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	3	14	theme	multiple	804:811	arg1	MS					824:825	MS	824:825	MS	824:825	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	3	14	theme	multiple	804:811	arg1	sclerosis					813:821	multiple sclerosis	804:821	multiple sclerosis (MS)	804:826	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	2	15	theme	ROS	243:245	arg1	species					247:253	ROS species	243:253	ROS species	243:253	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	16	dep	antibodies	575:584	arg1	Autoimmunity					604:615	Autoimmunity	604:615	Autoimmunity	604:615	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	16	dep	antibodies	575:584	arg1	Martensson					592:601	Martensson	592:601	Martensson	592:601	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	4	17	theme	autoimmune	834:843	arg1	disorder					845:852	This autoimmune disorder	829:852	This autoimmune disorder	829:852	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	10	18	theme	neutrophil	2030:2039	arg1	activity					2050:2057	low neutrophil elastase activity	2026:2057	low neutrophil elastase activity	2026:2057	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	3	19	theme	NET-related	701:711	arg1	changes					713:719	NET-related changes	701:719	NET-related changes in glycan composition	701:741	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	12	20	dep	degrade	2366:2372	arg1	partially					2356:2364	partially	2356:2364	partially	2356:2364	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	7	21	theme	corticosteroid	1611:1624	arg1	treatment					1626:1634	corticosteroid treatment	1611:1634	corticosteroid treatment	1611:1634	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	12	22	link	neutrophil-derived	2316:2333	arg1	proteases					2335:2343	neutrophil-derived proteases	2316:2343	neutrophil-derived proteases	2316:2343	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	9	23	theme	lectin	1870:1875	arg1	binding					1877:1883	Increased lectin binding	1860:1883	Increased lectin binding	1860:1883	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	5	24	theme	MS	1226:1227	arg1	patients					1229:1236	MS patients	1226:1236	MS patients	1226:1236	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	25	from	IgG	1182:1184	arg1	groups					1216:1221	five groups	1211:1221	five groups of MS patients	1211:1236	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	25	from	IgG	1182:1184	arg1	patients					1229:1236	MS patients	1226:1236	MS patients	1226:1236	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	7	26	theme	patients	1596:1603	arg1	group					1587:1591	the group	1583:1591	the group of patients under corticosteroid treatment	1583:1634	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	7	26	theme	patients	1596:1603	arg1	patients					1596:1603	patients	1596:1603	patients under corticosteroid treatment	1596:1634	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	4	27	theme	treatment	917:925	arg1	markers					886:892	no reliable detection markers	864:892	no reliable detection markers	864:892	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	4	27	theme	treatment	917:925	arg1	ways					909:912	established ways	897:912	established ways of treatment	897:925	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	11	28	theme	complexes	2217:2225	arg1	digestion					2175:2183	the digestion	2171:2183	the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops	2171:2273	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	10	29	theme	low	2063:2065	arg1	complexes					2096:2104	circulating immune complexes	2077:2104	circulating immune complexes	2077:2104	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	10	29	theme	low	2063:2065	arg1	amount					2067:2072	low amount	2063:2072	low amount	2063:2072	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	0	30	theme	complexes	76:84	arg1	composition					42:52	composition	42:52	composition of circulating immune complexes in multiple sclerosis	42:106	Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis.
30369266	1	31	theme	granules	158:165	arg1	content					135:141	the content	131:141	the content of neutrophils granules	131:165	During NET formation, the content of neutrophils granules is released into the intercellular milieu.
30369266	12	32	theme	internal	2427:2434	arg1	glycoepitops					2436:2447	internal glycoepitops	2427:2447	internal glycoepitops	2427:2447	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	5	33	theme	anti-B-cell	1378:1388	arg1	Ab					1401:1402	anti-B-cell monoclonal Ab	1378:1402	anti-B-cell monoclonal Ab	1378:1402	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	8	34	theme	IgG-IgM	1834:1840	arg1	complexes					1849:1857	circulating IgG-IgM immune complexes	1822:1857	circulating IgG-IgM immune complexes	1822:1857	Subsequent analysis demonstrated that sialic acid residues were exposed on free IgG and on circulating IgG-IgM immune complexes.
30369266	3	35	theme	IgG-IgM	776:782	arg1	complexes					791:799	IgG-IgM immune complexes	776:799	IgG-IgM immune complexes	776:799	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	0	36	theme	multiple	89:96	arg1	sclerosis					98:106	multiple sclerosis	89:106	multiple sclerosis	89:106	Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis.
30369266	5	37	theme	α2,6	1086:1089	arg1	SNA					1115:1117	α2,6 sialyl-specific lectins SNA	1086:1117	α2,6 sialyl-specific lectins SNA	1086:1117	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	38	theme	Ab	1401:1402	arg1	IgG					1182:1184	IgG	1182:1184	IgG	1182:1184	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	38	theme	Ab	1401:1402	arg1	corticosteroids					1324:1338	corticosteroids	1324:1338	corticosteroids (methylprednisolone) (12 persons)	1324:1372	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	9	39	theme	anti-myelin	1906:1916	arg1	protein					1924:1930	anti-myelin basic protein	1906:1930	anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab	1906:1992	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	4	40	contain	has	860:862	arg1	disorder					845:852	This autoimmune disorder	829:852	This autoimmune disorder	829:852	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	4	40	contain	has	860:862	arg2	markers					886:892	no reliable detection markers	864:892	no reliable detection markers	864:892	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	4	40	contain	has	860:862	arg2	ways					909:912	established ways	897:912	established ways of treatment	897:925	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	9	41	theme	protein	1924:1930	arg1	Ab					1964:1965	anti-myelin basic protein (one of the major autoAb in MS) Ab	1906:1965	anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab	1906:1992	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	2	42	theme	azurophilic	360:370	arg1	granules					372:379	neutrophil's azurophilic granules	347:379	neutrophil's azurophilic granules	347:379	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	9	43	from	autoAb	1950:1955	arg1	MS					1960:1961	MS	1960:1961	MS	1960:1961	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	6	44	theme	donors	1491:1496	arg1	donors					1491:1496	23 healthy donors	1480:1496	23 healthy donors	1480:1496	A group of 23 healthy donors served as control.
30369266	6	44	theme	donors	1491:1496	arg1	group					1471:1475	A group	1469:1475	A group of 23 healthy donors	1469:1496	A group of 23 healthy donors served as control.
30369266	7	45	theme	elastase	1552:1559	arg1	activity					1561:1568	neutrophil elastase activity	1541:1568	neutrophil elastase activity	1541:1568	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	0	46	from	composition	42:52	arg1	sclerosis					98:106	multiple sclerosis	89:106	multiple sclerosis	89:106	Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis.
30369266	3	47	from	possibility	686:696	arg1	composition					731:741	glycan composition	724:741	glycan composition	724:741	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	0	48	theme	Neutrophil-released	0:18	arg1	enzymes					20:26	Neutrophil-released enzymes	0:26	Neutrophil-released enzymes	0:26	Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis.
30369266	2	49	dep	secreted	413:420	arg1	JBC					457:459	JBC	457:459	JBC	457:459	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	49	dep	secreted	413:420	arg1	Thaysen-Andersen					439:454	Thaysen-Andersen	439:454	Thaysen-Andersen	439:454	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	8	50	theme	Subsequent	1731:1740	arg1	analysis					1742:1749	Subsequent analysis	1731:1749	Subsequent analysis	1731:1749	Subsequent analysis demonstrated that sialic acid residues were exposed on free IgG and on circulating IgG-IgM immune complexes.
30369266	12	51	theme	proteases	2335:2343	arg1	potential					2303:2311	the potential	2299:2311	the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops	2299:2447	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	5	52	theme	core	1130:1133	arg1	AAL					1163:1165	core α1,6-fucose specific lectin AAL	1130:1165	core α1,6-fucose specific lectin AAL	1130:1165	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	7	53	theme	Significant	1517:1527	arg1	increase					1529:1536	Significant increase	1517:1536	Significant increase	1517:1536	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	4	54	theme	accepted	943:950	arg1	therapy					963:969	widely accepted interferon therapy	936:969	widely accepted interferon therapy	936:969	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	5	55	theme	lectins	1107:1113	arg1	SNA					1115:1117	α2,6 sialyl-specific lectins SNA	1086:1117	α2,6 sialyl-specific lectins SNA	1086:1117	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	2	56	theme	autoantibodies	486:499	arg1	formation					473:481	formation	473:481	formation of autoantibodies to neutrophil beta-glucoronidase	473:532	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	3	57	from	composition	731:741	arg1	possibility					686:696	the possibility	682:696	the possibility of NET-related changes in glycan composition	682:741	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	0	58	theme	circulating	57:67	arg1	complexes					76:84	circulating immune complexes	57:84	circulating immune complexes	57:84	Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis.
30369266	7	59	theme	IgG	1716:1718	arg1	molecules					1720:1728	captured IgG molecules	1707:1728	captured IgG molecules	1707:1728	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	11	60	theme	high-molecular	2188:2201	arg1	complexes					2217:2225	high-molecular weight immune complexes	2188:2225	high-molecular weight immune complexes	2188:2225	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	9	61	dep	protein	1924:1930	arg1	autoAb					1950:1955	one of the major autoAb	1933:1955	one of the major autoAb in MS	1933:1961	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	5	62	theme	circulating	1170:1180	arg1	alemtuzumab					1444:1454	alemtuzumab	1444:1454	alemtuzumab	1444:1454	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	62	theme	circulating	1170:1180	arg1	persons					1459:1465	6 persons	1457:1465	6 persons	1457:1465	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	62	theme	circulating	1170:1180	arg1	persons					1432:1438	6 persons	1430:1438	6 persons	1430:1438	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	62	theme	circulating	1170:1180	arg1	persons					1408:1414	IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons	1182:1414	IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons	1182:1414	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	63	theme	interferon	1287:1296	arg1	β-1 b					1304:1308	interferon (IFN) β-1 b	1287:1308	interferon (IFN) β-1 b (15 persons)	1287:1321	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	63	theme	interferon	1287:1296	arg1	persons					1314:1320	15 persons	1311:1320	15 persons	1311:1320	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	11	64	theme	glycoepitops	2262:2273	arg1	exposure					2243:2250	subsequent exposure	2232:2250	subsequent exposure of hidden glycoepitops	2232:2273	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	7	65	theme	lectin	1689:1694	arg1	binding					1696:1702	sialyl-specific PSqL and SNA lectin binding	1660:1702	binding	1696:1702	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	4	66	theme	interesting	997:1007	arg1	condition					1018:1026	a particularly interesting clinical condition	982:1026	a particularly interesting clinical condition	982:1026	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	9	67	theme	serum	1985:1989	arg1	Ab					1991:1992	total serum Ab	1979:1992	total serum Ab	1979:1992	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	5	68	theme	IFN	1299:1301	arg1	β-1 b					1304:1308	interferon (IFN) β-1 b	1287:1308	interferon (IFN) β-1 b (15 persons)	1287:1321	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	68	theme	IFN	1299:1301	arg1	persons					1314:1320	15 persons	1311:1320	15 persons	1311:1320	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	69	theme	specific	1147:1154	arg1	AAL					1163:1165	core α1,6-fucose specific lectin AAL	1130:1165	core α1,6-fucose specific lectin AAL	1130:1165	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	2	70	theme	anti-MPO	566:573	arg1	Ab					587:588	Ab	587:588	Ab	587:588	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	70	theme	anti-MPO	566:573	arg1	antibodies					575:584	anti-MPO antibodies	566:584	anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992)	566:622	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	11	71	theme	immune	2210:2215	arg1	complexes					2217:2225	high-molecular weight immune complexes	2188:2225	high-molecular weight immune complexes	2188:2225	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	8	72	theme	sialic	1769:1774	arg1	residues					1781:1788	sialic acid residues	1769:1788	sialic acid residues	1769:1788	Subsequent analysis demonstrated that sialic acid residues were exposed on free IgG and on circulating IgG-IgM immune complexes.
30369266	5	73	theme	AAL	1163:1165	arg1	binding					1075:1081	binding	1075:1081	binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons)	1075:1466	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	11	74	with	digestion	2175:2183	arg1	exposure					2243:2250	subsequent exposure	2232:2250	subsequent exposure of hidden glycoepitops	2232:2273	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	7	75	theme	sialyl-specific	1660:1674	arg1	PSqL					1676:1679	sialyl-specific PSqL and SNA lectin binding	1660:1702	PSqL	1676:1679	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	11	76	theme	NETs	2140:2143	arg1	Incubation					2107:2116	Incubation	2107:2116	Incubation of in vitro generated NETs with human serum	2107:2160	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	5	77	dep	persons	1408:1414	arg1	Ocrelizumab					1417:1427	Ocrelizumab	1417:1427	Ocrelizumab	1417:1427	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	2	78	theme	Nat	310:312	arg1	Schauer					301:307	Schauer	301:307	Schauer	301:307	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	78	theme	Nat	310:312	arg1	Med					314:316	Nat Med	310:316	Nat Med	310:316	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	1	79	theme	intercellular	188:200	arg1	milieu					202:207	the intercellular milieu	184:207	the intercellular milieu	184:207	During NET formation, the content of neutrophils granules is released into the intercellular milieu.
30369266	5	80	theme	monoclonal	1390:1399	arg1	Ab					1401:1402	anti-B-cell monoclonal Ab	1378:1402	anti-B-cell monoclonal Ab	1378:1402	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	8	81	theme	free	1806:1809	arg1	IgG					1811:1813	free IgG	1806:1813	free IgG	1806:1813	Subsequent analysis demonstrated that sialic acid residues were exposed on free IgG and on circulating IgG-IgM immune complexes.
30369266	11	82	theme	hidden	2255:2260	arg1	glycoepitops					2262:2273	hidden glycoepitops	2255:2273	hidden glycoepitops	2255:2273	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	2	83	theme	neutrophil	504:513	arg1	beta-glucoronidase					515:532	neutrophil beta-glucoronidase	504:532	neutrophil beta-glucoronidase	504:532	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	11	84	theme	human	2150:2154	arg1	serum					2156:2160	human serum	2150:2160	human serum	2150:2160	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	4	85	theme	reliable	867:874	arg1	markers					886:892	no reliable detection markers	864:892	no reliable detection markers	864:892	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	7	86	from	increase	1529:1536	arg1	activity					1561:1568	neutrophil elastase activity	1541:1568	neutrophil elastase activity	1541:1568	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	10	87	theme	elastase	2041:2048	arg1	activity					2050:2057	low neutrophil elastase activity	2026:2057	low neutrophil elastase activity	2026:2057	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	3	88	theme	glycan	724:729	arg1	composition					731:741	glycan composition	724:741	glycan composition	724:741	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	8	89	theme	circulating	1822:1832	arg1	complexes					1849:1857	circulating IgG-IgM immune complexes	1822:1857	circulating IgG-IgM immune complexes	1822:1857	Subsequent analysis demonstrated that sialic acid residues were exposed on free IgG and on circulating IgG-IgM immune complexes.
30369266	5	90	theme	capture	1041:1047	arg1	lectin-ELISA					1049:1060	capture lectin-ELISA	1041:1060	capture lectin-ELISA	1041:1060	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	9	91	theme	Increased	1860:1868	arg1	binding					1877:1883	Increased lectin binding	1860:1883	Increased lectin binding	1860:1883	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	3	92	theme	changes	713:719	arg1	possibility					686:696	the possibility	682:696	the possibility of NET-related changes in glycan composition	682:741	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	8	93	theme	immune	1842:1847	arg1	complexes					1849:1857	circulating IgG-IgM immune complexes	1822:1857	circulating IgG-IgM immune complexes	1822:1857	Subsequent analysis demonstrated that sialic acid residues were exposed on free IgG and on circulating IgG-IgM immune complexes.
30369266	5	94	with	therapy	1274:1280	arg1	β-1 b					1304:1308	interferon (IFN) β-1 b	1287:1308	interferon (IFN) β-1 b (15 persons)	1287:1321	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	94	with	therapy	1274:1280	arg1	persons					1314:1320	15 persons	1311:1320	15 persons	1311:1320	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	10	95	theme	immune	2089:2094	arg1	complexes					2096:2104	circulating immune complexes	2077:2104	circulating immune complexes	2077:2104	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	5	96	theme	patients	1229:1236	arg1	groups					1216:1221	five groups	1211:1221	five groups of MS patients	1211:1236	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	96	theme	patients	1229:1236	arg1	patients					1229:1236	MS patients	1226:1236	MS patients	1226:1236	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	3	97	theme	IgG	758:760	arg1	molecules					762:770	IgG molecules	758:770	IgG molecules	758:770	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	2	98	contain	contain	391:397	arg2	glycosidases					399:410	glycosidases	399:410	glycosidases	399:410	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	98	contain	contain	391:397	arg1	content					336:342	the content	332:342	the content of neutrophil's azurophilic granules	332:379	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	99	theme	formed	256:261	arg1	NETs					263:266	formed NETs	256:266	formed NETs	256:266	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	1	100	theme	neutrophils	146:156	arg1	granules					158:165	neutrophils granules	146:165	neutrophils granules	146:165	During NET formation, the content of neutrophils granules is released into the intercellular milieu.
30369266	11	101	theme	weight	2203:2208	arg1	complexes					2217:2225	high-molecular weight immune complexes	2188:2225	high-molecular weight immune complexes	2188:2225	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	5	102	theme	complexes	1198:1206	arg1	alemtuzumab					1444:1454	alemtuzumab	1444:1454	alemtuzumab	1444:1454	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	102	theme	complexes	1198:1206	arg1	persons					1459:1465	6 persons	1457:1465	6 persons	1457:1465	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	102	theme	complexes	1198:1206	arg1	persons					1432:1438	6 persons	1430:1438	6 persons	1430:1438	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	102	theme	complexes	1198:1206	arg1	persons					1408:1414	IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons	1182:1414	IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons	1182:1414	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	3	103	from	changes	713:719	arg1	composition					731:741	glycan composition	724:741	glycan composition	724:741	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	10	104	theme	complexes	2096:2104	arg1	complexes					2096:2104	circulating immune complexes	2077:2104	circulating immune complexes	2077:2104	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	10	104	theme	complexes	2096:2104	arg1	activity					2050:2057	low neutrophil elastase activity	2026:2057	low neutrophil elastase activity	2026:2057	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	10	104	theme	complexes	2096:2104	arg1	amount					2067:2072	low amount	2063:2072	low amount	2063:2072	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	2	105	dep	degrade	282:288	arg1	Schauer					301:307	Schauer	301:307	Schauer	301:307	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	2	105	dep	degrade	282:288	arg1	Med					314:316	Nat Med	310:316	Nat Med	310:316	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	3	106	theme	immune	784:789	arg1	complexes					791:799	IgG-IgM immune complexes	776:799	IgG-IgM immune complexes	776:799	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	5	107	theme	sialyl-specific	1091:1105	arg1	SNA					1115:1117	α2,6 sialyl-specific lectins SNA	1086:1117	α2,6 sialyl-specific lectins SNA	1086:1117	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	10	108	theme	circulating	2077:2087	arg1	complexes					2096:2104	circulating immune complexes	2077:2104	circulating immune complexes	2077:2104	IFN therapy was accompanied by low neutrophil elastase activity and low amount of circulating immune complexes.
30369266	9	109	theme	basic	1918:1922	arg1	protein					1924:1930	anti-myelin basic protein	1906:1930	anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab	1906:1992	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	12	110	dep	modify	2348:2353	arg1	degrade					2366:2372	degrade	2366:2372	degrade	2366:2372	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	4	111	theme	established	897:907	arg1	ways					909:912	established ways	897:912	established ways of treatment	897:925	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	6	112	theme	healthy	1483:1489	arg1	donors					1491:1496	23 healthy donors	1480:1496	23 healthy donors	1480:1496	A group of 23 healthy donors served as control.
30369266	9	113	theme	of	1937:1938	arg1	autoAb					1950:1955	one of the major autoAb	1933:1955	one of the major autoAb in MS	1933:1961	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	5	114	theme	untreated	1239:1247	arg1	IgG					1182:1184	IgG	1182:1184	IgG	1182:1184	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	114	theme	untreated	1239:1247	arg1	corticosteroids					1324:1338	corticosteroids	1324:1338	corticosteroids (methylprednisolone) (12 persons)	1324:1372	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	3	115	dep	account	637:643	arg1	facts					651:655	these facts	645:655	account these facts	637:655	Taking into account these facts, we aimed to investigate the possibility of NET-related changes in glycan composition on circulating IgG molecules and IgG-IgM immune complexes in multiple sclerosis (MS).
30369266	1	116	theme	NET	116:118	arg1	formation					120:128	NET formation	116:128	NET formation	116:128	During NET formation, the content of neutrophils granules is released into the intercellular milieu.
30369266	7	117	theme	neutrophil	1541:1550	arg1	elastase					1552:1559	neutrophil elastase	1541:1559	neutrophil elastase activity	1541:1568	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	9	118	theme	major	1944:1948	arg1	autoAb					1950:1955	one of the major autoAb	1933:1955	one of the major autoAb in MS	1933:1961	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	5	119	theme	α1,6-fucose	1135:1145	arg1	AAL					1163:1165	core α1,6-fucose specific lectin AAL	1130:1165	core α1,6-fucose specific lectin AAL	1130:1165	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	0	120	theme	immune	69:74	arg1	complexes					76:84	circulating immune complexes	57:84	circulating immune complexes	57:84	Neutrophil-released enzymes can influence composition of circulating immune complexes in multiple sclerosis.
30369266	5	121	theme	SNA	1115:1117	arg1	binding					1075:1081	binding	1075:1081	binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons)	1075:1466	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	4	122	theme	interferon	952:961	arg1	therapy					963:969	widely accepted interferon therapy	936:969	widely accepted interferon therapy	936:969	This autoimmune disorder still has no reliable detection markers or established ways of treatment, besides widely accepted interferon therapy, making it a particularly interesting clinical condition.
30369266	12	123	theme	neutrophil-derived	2316:2333	arg1	proteases					2335:2343	neutrophil-derived proteases	2316:2343	neutrophil-derived proteases	2316:2343	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	2	124	theme	many	224:227	arg1	proteases					229:237	many proteases	224:237	many proteases	224:237	Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992).
30369266	5	125	theme	PSqL	1120:1123	arg1	binding					1075:1081	binding	1075:1081	binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons)	1075:1466	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	11	126	with	Incubation	2107:2116	arg1	serum					2156:2160	human serum	2150:2160	human serum	2150:2160	Incubation of in vitro generated NETs with human serum revealed the digestion of high-molecular weight immune complexes with subsequent exposure of hidden glycoepitops.
30369266	5	127	dep	untreated	1239:1247	arg1	persons					1253:1259	17 persons	1250:1259	17 persons	1250:1259	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	12	128	theme	Obtained	2276:2283	arg1	data					2285:2288	Obtained data	2276:2288	Obtained data	2276:2288	Obtained data indicate the potential of neutrophil-derived proteases to modify (partially degrade) circulating immune complexes leading to exposure of internal glycoepitops.
30369266	5	129	theme	IgG	1182:1184	arg1	alemtuzumab					1444:1454	alemtuzumab	1444:1454	alemtuzumab	1444:1454	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	129	theme	IgG	1182:1184	arg1	persons					1459:1465	6 persons	1457:1465	6 persons	1457:1465	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	129	theme	IgG	1182:1184	arg1	persons					1432:1438	6 persons	1430:1438	6 persons	1430:1438	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	5	129	theme	IgG	1182:1184	arg1	persons					1408:1414	IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons	1182:1414	IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons	1182:1414	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
30369266	7	130	theme	captured	1707:1714	arg1	molecules					1720:1728	captured IgG molecules	1707:1728	captured IgG molecules	1707:1728	Significant increase in neutrophil elastase activity, observed in the group of patients under corticosteroid treatment was also accompanied by sialyl-specific PSqL and SNA lectin binding to captured IgG molecules.
30369266	9	131	theme	total	1979:1983	arg1	Ab					1991:1992	total serum Ab	1979:1992	total serum Ab	1979:1992	Increased lectin binding was not observed for anti-myelin basic protein (one of the major autoAb in MS) Ab compared to total serum Ab.
30369266	5	132	theme	related	1190:1196	arg1	complexes					1198:1206	related complexes	1190:1206	related complexes	1190:1206	By applying capture lectin-ELISA, we analysed binding of α2,6 sialyl-specific lectins SNA, PSqL, and core α1,6-fucose specific lectin AAL to circulating IgG and related complexes in five groups of MS patients: untreated (17 persons); undergoing therapy with interferon (IFN) β-1 b (15 persons), corticosteroids (methylprednisolone) (12 persons) and anti-B-cell monoclonal Ab (12 persons: Ocrelizumab, 6 persons and alemtuzumab, 6 persons).
31096358	2	0	theme	urban	622:626	arg1	streams					649:655	15 first-order agricultural, urban and forest headwater streams	593:655	15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China	593:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	8	1	theme	carbon	1893:1898	arg1	processing					1900:1909	microbial carbon processing	1883:1909	microbial carbon processing	1883:1909	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	2	2	theme	subtropical	684:694	arg1	Lake					666:669	Lake	666:669	Lake	666:669	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	2	2	theme	subtropical	684:694	arg1	region					696:701	a subtropical region	682:701	a subtropical region of SE China	682:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	2	3	theme	agricultural	608:619	arg1	streams					649:655	15 first-order agricultural, urban and forest headwater streams	593:655	15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China	593:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	1	4	from	fate	304:307	arg1	ecosystems					353:362	stream ecosystems	346:362	stream ecosystems	346:362	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	4	5	link	soil-derived	1171:1182	arg1	DOM					1195:1197	microbially soil-derived humic-like DOM	1159:1197	microbially soil-derived humic-like DOM	1159:1197	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	4	6	dep	neutrals	1242:1249	arg1	e.g.					1236:1239	e.g.	1236:1239	e.g.	1236:1239	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	9	7	theme	labile	2397:2402	arg1	substrates					2404:2413	less labile substrates	2392:2413	less labile substrates	2392:2413	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	8	8	theme	explainable	1767:1777	arg1	quality					1758:1764	DOM quality	1754:1764	DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%)	1754:1840	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	8	theme	explainable	1767:1777	arg1	variables					1779:1787	explainable variables	1767:1787	explainable variables: molecular source	1767:1805	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	2	9	with	chromatography	409:422	arg1	matrices					462:469	fluorescence excitation-emission matrices	429:469	fluorescence excitation-emission matrices	429:469	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	2	9	with	chromatography	409:422	arg1	biomarkers					505:514	absorbance and lignin biomarkers	483:514	biomarkers	505:514	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	2	10	theme	forest	632:637	arg1	streams					649:655	15 first-order agricultural, urban and forest headwater streams	593:655	15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China	593:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	3	11	theme	agricultural	751:762	arg1	land					764:767	both urban and agricultural land	736:767	both urban and agricultural land	736:767	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	10	12	from	changes	2609:2615	arg1	fate					2624:2627	the fate	2620:2627	the fate of organic carbon moving through freshwater ecosystems	2620:2682	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	9	13	theme	higher	1956:1961	arg1	mineralized					2015:2025	mineralized	2015:2025	mineralized	2015:2025	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	9	13	theme	higher	1956:1961	arg1	proportion					1963:1972	A higher proportion	1954:1972	A higher proportion of DOM from urban streams	1954:1998	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	3	14	theme	urban	741:745	arg1	land					764:767	both urban and agricultural land	736:767	both urban and agricultural land	736:767	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	9	15	theme	urban	1986:1990	arg1	streams					1992:1998	urban streams	1986:1998	urban streams	1986:1998	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	7	16	theme	protein-like	1685:1696	arg1	fractions					1698:1706	autochthonous protein-like fractions	1671:1706	autochthonous protein-like fractions	1671:1706	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	9	17	from	proportion	1963:1972	arg1	streams					1992:1998	urban streams	1986:1998	urban streams	1986:1998	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	4	18	theme	DOM	1116:1118	arg1	DOM					1116:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM	1058:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams	1058:1144	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	4	18	theme	DOM	1116:1118	arg1	amounts					1047:1053	the amounts	1043:1053	the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams	1043:1144	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	9	19	theme	inorganic	2192:2200	arg1	nitrogen					2202:2209	inorganic nitrogen	2192:2209	inorganic nitrogen	2192:2209	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	1	20	theme	source	377:382	arg1	pathways					384:391	nonpoint source pathways	368:391	nonpoint source pathways	368:391	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	4	21	theme	soil-derived	1171:1182	arg1	DOM					1195:1197	microbially soil-derived humic-like DOM	1159:1197	microbially soil-derived humic-like DOM	1159:1197	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	1	22	theme	Landscape	117:125	arg1	urbanization					127:138	Landscape urbanization	117:138	Landscape urbanization	117:138	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	3	23	theme	C/N	843:845	arg1	ratio					847:851	a lower C/N ratio	835:851	a lower C/N ratio	835:851	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	7	24	theme	high	1656:1659	arg1	values					1661:1666	high values	1656:1666	high values of autochthonous protein-like fractions	1656:1706	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	2	25	theme	DOM	586:588	arg1	characteristics					548:562	the characteristics	544:562	the characteristics	544:562	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	2	25	theme	DOM	586:588	arg1	fate					578:581	microbial fate	568:581	microbial fate	568:581	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	10	26	theme	microbial	2561:2569	arg1	processing					2578:2587	stream microbial carbon processing	2554:2587	stream microbial carbon processing	2554:2587	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	3	27	theme	organic	809:815	arg1	DOC					825:827	DOC	825:827	DOC	825:827	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	3	27	theme	organic	809:815	arg1	matter					817:822	dissolved organic matter	799:822	dissolved organic matter (DOC)	799:828	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	4	28	theme	headwater	959:967	arg1	streams					969:975	forest-impacted headwater streams	943:975	forest-impacted headwater streams	943:975	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	6	29	theme	Natural	1409:1415	arg1	watersheds					1417:1426	Natural watersheds	1409:1426	Natural watersheds	1409:1426	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	1	30	theme	organic	322:328	arg1	DOM					338:340	DOM	338:340	DOM	338:340	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	1	30	theme	organic	322:328	arg1	matter					330:335	dissolved organic matter	312:335	dissolved organic matter (DOM)	312:341	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	2	31	theme	lignin	498:503	arg1	biomarkers					505:514	absorbance and lignin biomarkers	483:514	biomarkers	505:514	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	0	32	from	origins	16:22	arg1	streams					108:114	agro-urban headwater streams	87:114	agro-urban headwater streams	87:114	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	0	33	theme	organic	69:75	arg1	matter					77:82	dissolved organic matter	59:82	dissolved organic matter	59:82	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	7	34	theme	protein-like	1604:1615	arg1	fractions					1617:1625	terrestrial humic-like and protein-like fractions	1577:1625	terrestrial humic-like and protein-like fractions	1577:1625	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	10	35	from	differences	2443:2453	arg1	properties					2487:2496	stream-DOM and environmental properties	2458:2496	stream-DOM and environmental properties due to urbanization and farming practices	2458:2538	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	9	36	theme	DOM	2261:2263	arg1	fraction					2249:2256	a significant fraction	2235:2256	a significant fraction of DOM from agricultural and forest streams	2235:2300	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	3	37	dep	cover	769:773	arg1	increased					775:783	increased	775:783	cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio	769:851	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	7	38	contain	had	1652:1654	arg2	values					1661:1666	high values	1656:1666	high values of autochthonous protein-like fractions	1656:1706	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	7	38	contain	had	1652:1654	arg1	watersheds					1641:1650	urbanized watersheds	1631:1650	urbanized watersheds	1631:1650	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	3	39	theme	DOC	879:881	arg1	majority					867:874	the majority	863:874	the majority of DOC	863:881	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	7	40	theme	humic-like	1589:1598	arg1	fractions					1617:1625	terrestrial humic-like and protein-like fractions	1577:1625	terrestrial humic-like and protein-like fractions	1577:1625	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	8	41	dep	variables	1779:1787	arg1	%					1813:1813	43.29%	1808:1813	43.29%	1808:1813	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	41	dep	variables	1779:1787	arg1	source					1800:1805	molecular source	1790:1805	explainable variables: molecular source	1767:1805	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	41	dep	variables	1779:1787	arg1	molecular-weight					1816:1831	molecular-weight	1816:1831	molecular-weight	1816:1831	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	41	dep	variables	1779:1787	arg1	%					1839:1839	29.74%	1834:1839	29.74%	1834:1839	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	9	42	theme	agricultural	2270:2281	arg1	streams					2294:2300	agricultural and forest streams	2270:2300	agricultural and forest streams	2270:2300	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	0	43	theme	headwater	98:106	arg1	streams					108:114	agro-urban headwater streams	87:114	agro-urban headwater streams	87:114	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	1	44	theme	stream	346:351	arg1	ecosystems					353:362	stream ecosystems	346:362	stream ecosystems	346:362	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	4	45	theme	OM	1014:1015	arg1	molecularity					998:1009	molecularity	998:1009	molecularity	998:1009	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	4	45	theme	OM	1014:1015	arg1	aromaticity					982:992	aromaticity	982:992	aromaticity	982:992	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	0	46	from	composition	25:35	arg1	streams					108:114	agro-urban headwater streams	87:114	agro-urban headwater streams	87:114	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	4	47	theme	low	1203:1205	arg1	substances					1224:1233	low molecular-weight substances	1203:1233	low molecular-weight substances (e.g., neutrals and acids)	1203:1260	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	5	48	theme	seasonal	1357:1364	arg1	variability					1366:1376	the seasonal variability	1353:1376	the seasonal variability of stream DOM biogeochemistry	1353:1406	Human-influenced land use also influenced the seasonal variability of stream DOM biogeochemistry.
31096358	9	49	theme	forest	2287:2292	arg1	streams					2294:2300	agricultural and forest streams	2270:2300	agricultural and forest streams	2270:2300	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	8	50	theme	microbial	1883:1891	arg1	processing					1900:1909	microbial carbon processing	1883:1909	microbial carbon processing	1883:1909	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	51	theme	inorganic	1924:1932	arg1	nutrients					1934:1942	inorganic nutrients	1924:1942	inorganic nutrients (17.29%)	1924:1951	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	51	theme	inorganic	1924:1932	arg1	%					1950:1950	17.29%	1945:1950	17.29%	1945:1950	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	3	52	theme	terrestrial	896:906	arg1	substances					919:928	terrestrial humic-like substances	896:928	terrestrial humic-like substances	896:928	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	9	53	theme	humic	2090:2094	arg1	substances					2153:2162	humic and nonhumic (e.g., protein, polysaccharides and lignin) substances	2090:2162	humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus	2090:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	2	54	theme	excitation-emission	442:460	arg1	matrices					462:469	fluorescence excitation-emission matrices	429:469	fluorescence excitation-emission matrices	429:469	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	10	55	theme	carbon	2640:2645	arg1	fate					2624:2627	the fate	2620:2627	the fate of organic carbon moving through freshwater ecosystems	2620:2682	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	5	56	theme	Human-influenced	1311:1326	arg1	use					1333:1335	Human-influenced land use	1311:1335	Human-influenced land use	1311:1335	Human-influenced land use also influenced the seasonal variability of stream DOM biogeochemistry.
31096358	9	57	from	streams	1992:1998	arg1	mineralized					2015:2025	mineralized	2015:2025	mineralized	2015:2025	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	9	57	from	streams	1992:1998	arg1	DOM					1977:1979	DOM	1977:1979	DOM from urban streams	1977:1998	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	9	57	from	streams	1992:1998	arg1	proportion					1963:1972	A higher proportion	1954:1972	A higher proportion of DOM from urban streams	1954:1998	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	2	58	theme	absorbance	483:492	arg1	biomarkers					505:514	absorbance and lignin biomarkers	483:514	biomarkers	505:514	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	4	59	theme	agricultural	1275:1286	arg1	streams					1288:1294	agricultural streams	1275:1294	agricultural streams	1275:1294	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	2	60	theme	Size-exclusion	394:407	arg1	chromatography					409:422	Size-exclusion chromatography	394:422	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers	394:514	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	6	61	theme	DOC	1442:1444	arg1	loads					1455:1459	high DOC specific loads	1437:1459	high DOC specific loads	1437:1459	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	1	62	theme	ultimate	295:302	arg1	fate					304:307	ultimate fate	295:307	ultimate fate	295:307	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	9	63	theme	nonhumic	2100:2107	arg1	substances					2153:2162	humic and nonhumic (e.g., protein, polysaccharides and lignin) substances	2090:2162	humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus	2090:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	0	64	theme	microbial	41:49	arg1	fate					51:54	microbial fate	41:54	microbial fate	41:54	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	4	65	theme	anthropogenic/aquagenic	1058:1080	arg1	DOM					1116:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM	1058:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams	1058:1144	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	1	66	dep	little	214:219	arg1	known					221:225	known	221:225	known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways	221:391	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	4	67	dep	substances	1224:1233	arg1	acids					1255:1259	acids	1255:1259	acids	1255:1259	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	4	67	dep	substances	1224:1233	arg1	neutrals					1242:1249	neutrals	1242:1249	neutrals	1242:1249	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	0	68	dep	origins	16:22	arg1	the					12:14	the	12:14	the	12:14	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	4	69	theme	acid-like	1089:1097	arg1	DOM					1116:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM	1058:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams	1058:1144	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	9	70	theme	significant	2237:2247	arg1	fraction					2249:2256	a significant fraction	2235:2256	a significant fraction of DOM from agricultural and forest streams	2235:2300	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	5	71	theme	DOM	1388:1390	arg1	biogeochemistry					1392:1406	stream DOM biogeochemistry	1381:1406	stream DOM biogeochemistry	1381:1406	Human-influenced land use also influenced the seasonal variability of stream DOM biogeochemistry.
31096358	6	72	theme	rainy	1492:1496	arg1	season					1498:1503	the rainy season	1488:1503	the rainy season (high-flow period)	1488:1522	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	6	72	theme	rainy	1492:1496	arg1	period					1516:1521	high-flow period	1506:1521	high-flow period	1506:1521	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	1	73	theme	land	253:256	arg1	use					258:260	urban and agriculture land use	231:260	urban and agriculture land use	231:260	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	4	74	dep	aromaticity	982:992	arg1	the					978:980	the	978:980	the	978:980	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	2	75	theme	first-order	596:606	arg1	streams					649:655	15 first-order agricultural, urban and forest headwater streams	593:655	15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China	593:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	4	76	theme	urban	1132:1136	arg1	streams					1138:1144	urban streams	1132:1144	urban streams	1132:1144	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	9	77	theme	substances	2153:2162	arg1	utilization					2075:2085	the inefficient utilization	2059:2085	the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus	2059:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	1	78	from	quality	283:289	arg1	ecosystems					353:362	stream ecosystems	346:362	stream ecosystems	346:362	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	8	79	theme	DOM	1754:1756	arg1	factor					1866:1871	the most prominent factor	1847:1871	the most prominent factor impacting microbial carbon processing	1847:1909	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	79	theme	DOM	1754:1756	arg1	quality					1758:1764	DOM quality	1754:1764	DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%)	1754:1840	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	79	theme	DOM	1754:1756	arg1	variables					1779:1787	explainable variables	1767:1787	explainable variables: molecular source	1767:1805	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	1	80	theme	stream	185:190	arg1	ecosystems					192:201	stream ecosystems	185:201	stream ecosystems	185:201	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	2	81	theme	headwater	639:647	arg1	streams					649:655	15 first-order agricultural, urban and forest headwater streams	593:655	15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China	593:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	10	82	theme	urbanization	2505:2516	arg1	practices					2530:2538	urbanization and farming practices	2505:2538	urbanization and farming practices	2505:2538	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	1	83	from	quantity	273:280	arg1	ecosystems					353:362	stream ecosystems	346:362	stream ecosystems	346:362	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	9	84	theme	substrates	2404:2413	arg1	presence					2380:2387	the presence	2376:2387	the presence of less labile substrates	2376:2413	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	7	85	theme	fractions	1698:1706	arg1	values					1661:1666	high values	1656:1666	high values of autochthonous protein-like fractions	1656:1706	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	4	86	theme	protein-like	1103:1114	arg1	DOM					1116:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM	1058:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams	1058:1144	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	10	87	theme	due	2498:2500	arg1	properties					2487:2496	stream-DOM and environmental properties	2458:2496	stream-DOM and environmental properties due to urbanization and farming practices	2458:2538	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	9	88	theme	higher	2175:2180	arg1	levels					2182:2187	well as higher levels	2167:2187	well as higher levels of inorganic nitrogen and phosphorus	2167:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	7	89	theme	autochthonous	1671:1683	arg1	fractions					1698:1706	autochthonous protein-like fractions	1671:1706	autochthonous protein-like fractions	1671:1706	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	2	90	theme	microbial	568:576	arg1	fate					578:581	microbial fate	568:581	microbial fate	568:581	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	1	91	theme	nonpoint	368:375	arg1	pathways					384:391	nonpoint source pathways	368:391	nonpoint source pathways	368:391	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	8	92	theme	molecular	1790:1798	arg1	source					1800:1805	molecular source	1790:1805	explainable variables: molecular source	1767:1805	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	9	93	dep	protein	2116:2122	arg1	e.g.					2110:2113	e.g.	2110:2113	e.g.	2110:2113	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	4	94	theme	humic-like	1184:1193	arg1	DOM					1195:1197	microbially soil-derived humic-like DOM	1159:1197	microbially soil-derived humic-like DOM	1159:1197	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	10	95	theme	farming	2522:2528	arg1	practices					2530:2538	urbanization and farming practices	2505:2538	urbanization and farming practices	2505:2538	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	9	96	theme	nitrogen	2202:2209	arg1	levels					2182:2187	well as higher levels	2167:2187	well as higher levels of inorganic nitrogen and phosphorus	2167:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	2	97	theme	SE	706:707	arg1	China					709:713	SE China	706:713	SE China	706:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	10	98	theme	carbon	2571:2576	arg1	processing					2578:2587	stream microbial carbon processing	2554:2587	stream microbial carbon processing	2554:2587	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	9	99	theme	phosphorus	2215:2224	arg1	levels					2182:2187	well as higher levels	2167:2187	well as higher levels of inorganic nitrogen and phosphorus	2167:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	7	100	theme	urbanized	1631:1639	arg1	watersheds					1641:1650	urbanized watersheds	1631:1650	urbanized watersheds	1631:1650	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	10	101	theme	stream	2554:2559	arg1	processing					2578:2587	stream microbial carbon processing	2554:2587	stream microbial carbon processing	2554:2587	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	3	102	theme	matter	817:822	arg1	DOC					825:827	DOC	825:827	DOC	825:827	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	3	102	theme	matter	817:822	arg1	matter					817:822	dissolved organic matter	799:822	dissolved organic matter (DOC)	799:828	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	3	102	theme	matter	817:822	arg1	amount					789:794	the amount	785:794	the amount of dissolved organic matter (DOC)	785:828	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	0	103	theme	dissolved	59:67	arg1	matter					77:82	dissolved organic matter	59:82	dissolved organic matter	59:82	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	9	104	from	streams	2294:2300	arg1	fraction					2249:2256	a significant fraction	2235:2256	a significant fraction of DOM from agricultural and forest streams	2235:2300	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	1	105	theme	intensive	144:152	arg1	agriculture					154:164	intensive agriculture	144:164	intensive agriculture	144:164	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	3	106	theme	lower	837:841	arg1	ratio					847:851	a lower C/N ratio	835:851	a lower C/N ratio	835:851	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	7	107	theme	fractions	1617:1625	arg1	amount					1567:1572	a higher amount	1558:1572	a higher amount of terrestrial humic-like and protein-like fractions	1558:1625	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	7	107	theme	fractions	1617:1625	arg1	fractions					1617:1625	terrestrial humic-like and protein-like fractions	1577:1625	terrestrial humic-like and protein-like fractions	1577:1625	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	4	108	theme	forest-impacted	943:957	arg1	streams					969:975	forest-impacted headwater streams	943:975	forest-impacted headwater streams	943:975	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	10	109	theme	bottom-up	2599:2607	arg1	changes					2609:2615	bottom-up changes	2599:2615	bottom-up changes in the fate of organic carbon moving through freshwater ecosystems	2599:2682	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	3	110	theme	dissolved	799:807	arg1	DOC					825:827	DOC	825:827	DOC	825:827	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	3	110	theme	dissolved	799:807	arg1	matter					817:822	dissolved organic matter	799:822	dissolved organic matter (DOC)	799:828	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	0	111	theme	matter	77:82	arg1	origins					16:22	origins	16:22	origins	16:22	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	0	111	theme	matter	77:82	arg1	composition					25:35	composition	25:35	composition	25:35	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	0	111	theme	matter	77:82	arg1	fate					51:54	microbial fate	41:54	microbial fate	41:54	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	1	112	theme	matter	330:335	arg1	quality					283:289	quality	283:289	quality	283:289	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	1	112	theme	matter	330:335	arg1	fate					304:307	ultimate fate	295:307	ultimate fate	295:307	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	1	112	theme	matter	330:335	arg1	quantity					273:280	quantity	273:280	quantity	273:280	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	1	113	dep	quantity	273:280	arg1	the					269:271	the	269:271	the	269:271	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	9	114	theme	carbon	2030:2035	arg1	dioxide					2037:2043	carbon dioxide	2030:2043	carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus	2030:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	0	115	theme	agro-urban	87:96	arg1	streams					108:114	agro-urban headwater streams	87:114	agro-urban headwater streams	87:114	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	7	116	theme	terrestrial	1577:1587	arg1	fractions					1617:1625	terrestrial humic-like and protein-like fractions	1577:1625	terrestrial humic-like and protein-like fractions	1577:1625	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	0	117	from	fate	51:54	arg1	streams					108:114	agro-urban headwater streams	87:114	agro-urban headwater streams	87:114	Deciphering the origins, composition and microbial fate of dissolved organic matter in agro-urban headwater streams.
31096358	4	118	theme	molecular-weight	1207:1222	arg1	substances					1224:1233	low molecular-weight substances	1203:1233	low molecular-weight substances (e.g., neutrals and acids)	1203:1260	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	8	119	theme	prominent	1856:1864	arg1	factor					1866:1871	the most prominent factor	1847:1871	the most prominent factor impacting microbial carbon processing	1847:1909	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	119	theme	prominent	1856:1864	arg1	quality					1758:1764	DOM quality	1754:1764	DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%)	1754:1840	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	9	120	theme	inefficient	2063:2073	arg1	utilization					2075:2085	the inefficient utilization	2059:2085	the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus	2059:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	2	121	theme	China	709:713	arg1	Lake					666:669	Lake	666:669	Lake	666:669	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	2	121	theme	China	709:713	arg1	region					696:701	a subtropical region	682:701	a subtropical region of SE China	682:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	9	122	theme	due	2052:2054	arg1	dioxide					2037:2043	carbon dioxide	2030:2043	carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus	2030:2224	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	3	123	theme	humic-like	908:917	arg1	substances					919:928	terrestrial humic-like substances	896:928	terrestrial humic-like substances	896:928	Results showed that both urban and agricultural land cover increased the amount of dissolved organic matter (DOC) with a lower C/N ratio, and that the majority of DOC was bound to terrestrial humic-like substances.
31096358	2	124	theme	fluorescence	429:440	arg1	matrices					462:469	fluorescence excitation-emission matrices	429:469	fluorescence excitation-emission matrices	429:469	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	10	125	theme	organic	2632:2638	arg1	carbon					2640:2645	organic carbon	2632:2645	organic carbon moving through freshwater ecosystems	2632:2682	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	5	126	theme	land	1328:1331	arg1	use					1333:1335	Human-influenced land use	1311:1335	Human-influenced land use	1311:1335	Human-influenced land use also influenced the seasonal variability of stream DOM biogeochemistry.
31096358	6	127	theme	specific	1446:1453	arg1	loads					1455:1459	high DOC specific loads	1437:1459	high DOC specific loads	1437:1459	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	10	128	theme	environmental	2473:2485	arg1	properties					2487:2496	stream-DOM and environmental properties	2458:2496	stream-DOM and environmental properties due to urbanization and farming practices	2458:2538	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	5	129	theme	biogeochemistry	1392:1406	arg1	variability					1366:1376	the seasonal variability	1353:1376	the seasonal variability of stream DOM biogeochemistry	1353:1406	Human-influenced land use also influenced the seasonal variability of stream DOM biogeochemistry.
31096358	9	130	theme	microbial	2318:2326	arg1	production					2328:2337	microbial production	2318:2337	microbial production	2318:2337	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	6	131	theme	high	1437:1440	arg1	loads					1455:1459	high DOC specific loads	1437:1459	high DOC specific loads	1437:1459	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	7	132	theme	higher	1560:1565	arg1	amount					1567:1572	a higher amount	1558:1572	a higher amount of terrestrial humic-like and protein-like fractions	1558:1625	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	7	132	theme	higher	1560:1565	arg1	fractions					1617:1625	terrestrial humic-like and protein-like fractions	1577:1625	terrestrial humic-like and protein-like fractions	1577:1625	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	10	133	theme	stream-DOM	2458:2467	arg1	properties					2487:2496	stream-DOM and environmental properties	2458:2496	stream-DOM and environmental properties due to urbanization and farming practices	2458:2538	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	2	134	from	streams	649:655	arg1	Lake					666:669	Lake	666:669	Lake	666:669	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	2	134	from	streams	649:655	arg1	region					696:701	a subtropical region	682:701	a subtropical region of SE China	682:713	Size-exclusion chromatography with fluorescence excitation-emission matrices, as well as absorbance and lignin biomarkers were applied to investigate the characteristics and microbial fate of DOM in 15 first-order agricultural, urban and forest headwater streams in Taihu Lake Watershed, a subtropical region of SE China.
31096358	10	135	theme	freshwater	2662:2671	arg1	ecosystems					2673:2682	freshwater ecosystems	2662:2682	freshwater ecosystems	2662:2682	Our findings indicate that differences in stream-DOM and environmental properties due to urbanization and farming practices may influence stream microbial carbon processing and cause bottom-up changes in the fate of organic carbon moving through freshwater ecosystems.
31096358	8	136	theme	Redundancy	1714:1723	arg1	analysis					1725:1732	Redundancy analysis	1714:1732	Redundancy analysis (RDA)	1714:1738	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	8	136	theme	Redundancy	1714:1723	arg1	RDA					1735:1737	RDA	1735:1737	RDA	1735:1737	Redundancy analysis (RDA) revealed that DOM quality (explainable variables: molecular source, 43.29%; molecular-weight, 29.74%) were the most prominent factor impacting microbial carbon processing, followed by inorganic nutrients (17.29%).
31096358	1	137	theme	dissolved	312:320	arg1	DOM					338:340	DOM	338:340	DOM	338:340	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	1	137	theme	dissolved	312:320	arg1	matter					330:335	dissolved organic matter	312:335	dissolved organic matter (DOM)	312:341	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	9	138	theme	DOM	1977:1979	arg1	mineralized					2015:2025	mineralized	2015:2025	mineralized	2015:2025	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	9	138	theme	DOM	1977:1979	arg1	proportion					1963:1972	A higher proportion	1954:1972	A higher proportion of DOM from urban streams	1954:1998	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	9	139	theme	recalcitrant-DOM	2347:2362	arg1	pool					2364:2367	the recalcitrant-DOM pool	2343:2367	the recalcitrant-DOM pool	2343:2367	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
31096358	6	140	theme	high-flow	1506:1514	arg1	season					1498:1503	the rainy season	1488:1503	the rainy season (high-flow period)	1488:1522	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	6	140	theme	high-flow	1506:1514	arg1	period					1516:1521	high-flow period	1506:1521	high-flow period	1506:1521	Natural watersheds produced high DOC specific loads and concentrations only in the rainy season (high-flow period).
31096358	1	141	theme	urban	231:235	arg1	use					258:260	urban and agriculture land use	231:260	urban and agriculture land use	231:260	Landscape urbanization and intensive agriculture dramatically alter stream ecosystems, but it is little known how urban and agriculture land use change the quantity, quality and ultimate fate of dissolved organic matter (DOM) in stream ecosystems via nonpoint source pathways.
31096358	7	142	theme	Agricultural	1525:1536	arg1	streams					1538:1544	Agricultural streams	1525:1544	Agricultural streams	1525:1544	Agricultural streams contributed a higher amount of terrestrial humic-like and protein-like fractions and urbanized watersheds had high values of autochthonous protein-like fractions only.
31096358	4	143	theme	fulvic	1082:1087	arg1	DOM					1116:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM	1058:1118	anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams	1058:1144	Compared to forest-impacted headwater streams, the aromaticity and molecularity of OM were greatly decreased as the amounts of anthropogenic/aquagenic fulvic acid-like and protein-like DOM enriched in urban streams, and that of microbially soil-derived humic-like DOM and low molecular-weight substances (e.g., neutrals and acids) increased in agricultural streams, respectively.
31096358	5	144	theme	stream	1381:1386	arg1	biogeochemistry					1392:1406	stream DOM biogeochemistry	1381:1406	stream DOM biogeochemistry	1381:1406	Human-influenced land use also influenced the seasonal variability of stream DOM biogeochemistry.
31096358	9	145	theme	due	2369:2371	arg1	production					2328:2337	microbial production	2318:2337	microbial production	2318:2337	A higher proportion of DOM from urban streams was eventually mineralized to carbon dioxide mainly due to the inefficient utilization of humic and nonhumic (e.g., protein, polysaccharides and lignin) substances as well as higher levels of inorganic nitrogen and phosphorus, whereas a significant fraction of DOM from agricultural and forest streams tended to enter microbial production and the recalcitrant-DOM pool due to the presence of less labile substrates.
30894463	11	0	theme	gene	2041:2044	arg1	therapy					2046:2052	gene therapy	2041:2052	gene therapy	2041:2052	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	7	1	theme	systemic	1066:1073	arg1	administration					1075:1088	systemic administration	1066:1088	systemic administration	1066:1088	In contrast, AAV1 shows strong SIA dependency and does not transduce the CNS after systemic administration and, instead, transduces the vasculature and the liver.
30894463	11	2	theme	transduction	1777:1788	arg1	profile					1790:1796	the CNS transduction profile	1769:1796	the CNS transduction profile of AAV capsids.IMPORTANCE Understanding	1769:1836	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	9	3	theme	reciprocal	1345:1354	arg1	swap					1356:1359	the reciprocal swap	1341:1359	the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1)	1341:1406	In corollary, the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1) attenuated CNS transduction relative to that of AAVrh.10.
30894463	5	4	with	variants	749:756	arg1	footprints					775:784	altered SIA footprints	763:784	altered SIA footprints	763:784	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	3	5	from	footprint	608:616	arg1	AAV1					621:624	AAV1	621:624	AAV1	621:624	Here, we establish through structural modeling that this footprint overlaps in part the sialic acid (SIA) footprint on AAV1.
30894463	9	6	theme	AAV1RX	1368:1373	arg1	footprint					1375:1383	the AAV1RX footprint	1364:1383	the AAV1RX footprint	1364:1383	In corollary, the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1) attenuated CNS transduction relative to that of AAVrh.10.
30894463	8	7	theme	intermediate	1181:1192	arg1	phenotype					1206:1214	an intermediate SIA binding phenotype	1178:1214	an intermediate SIA binding phenotype	1178:1214	The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10.
30894463	10	8	theme	capsid	1522:1527	arg1	region					1538:1543	the capsid variable region 1	1518:1545	the capsid variable region 1 (VR1) of AAV1 and AAVrh.10	1518:1572	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	10	8	theme	capsid	1522:1527	arg1	VR1					1548:1550	VR1	1548:1550	VR1	1548:1550	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	11	9	theme	Goldilocks	1701:1710	arg1	model					1712:1716	a Goldilocks model	1699:1716	a Goldilocks model	1699:1716	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	2	10	theme	structural	315:324	arg1	footprint					326:334	a structural footprint	313:334	a structural footprint	313:334	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	8	11	theme	binding	1198:1204	arg1	phenotype					1206:1214	an intermediate SIA binding phenotype	1178:1214	an intermediate SIA binding phenotype	1178:1214	The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10.
30894463	3	12	theme	structural	529:538	arg1	modeling					540:547	structural modeling	529:547	structural modeling	529:547	Here, we establish through structural modeling that this footprint overlaps in part the sialic acid (SIA) footprint on AAV1.
30894463	8	13	theme	AAV1RX	1150:1155	arg1	variant					1157:1163	The AAV1RX variant	1146:1163	The AAV1RX variant	1146:1163	The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10.
30894463	9	14	theme	CNS	1419:1421	arg1	transduction					1423:1434	CNS transduction	1419:1434	CNS transduction relative to that of AAVrh.10	1419:1463	In corollary, the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1) attenuated CNS transduction relative to that of AAVrh.10.
30894463	11	15	theme	optimal	1727:1733	arg1	interactions					1742:1753	wherein optimal glycan interactions	1719:1753	wherein optimal glycan interactions	1719:1753	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	7	16	theme	strong	1007:1012	arg1	dependency					1018:1027	strong SIA dependency	1007:1027	strong SIA dependency	1007:1027	In contrast, AAV1 shows strong SIA dependency and does not transduce the CNS after systemic administration and, instead, transduces the vasculature and the liver.
30894463	6	17	theme	SIA	902:904	arg1	binding					906:912	ablated SIA binding	894:912	ablated SIA binding	894:912	Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency.
30894463	11	18	theme	recombinant	2011:2021	arg1	vectors					2029:2035	new recombinant viral vectors	2007:2035	new recombinant viral vectors for gene therapy	2007:2052	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	12	19	theme	gene	2264:2267	arg1	transfer					2269:2276	efficient gene transfer	2254:2276	efficient gene transfer to neurons	2254:2287	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	1	20	theme	nervous	133:139	arg1	system					141:146	Central nervous system	125:146	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors	125:243	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	1	20	theme	nervous	133:139	arg1	CNS					149:151	CNS	149:151	CNS	149:151	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	6	21	with	CNS	946:948	arg1	efficiency					971:980	low to moderate efficiency	955:980	low to moderate efficiency	955:980	Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency.
30894463	8	22	theme	brain	1240:1244	arg1	parenchyma					1246:1255	the brain parenchyma	1236:1255	the brain parenchyma	1236:1255	The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10.
30894463	3	23	theme	acid	597:600	arg1	footprint					608:616	the sialic acid (SIA) footprint	586:616	the sialic acid (SIA) footprint on AAV1	586:624	Here, we establish through structural modeling that this footprint overlaps in part the sialic acid (SIA) footprint on AAV1.
30894463	9	24	theme	relative	1436:1443	arg1	transduction					1423:1434	CNS transduction	1419:1434	CNS transduction relative to that of AAVrh.10	1419:1463	In corollary, the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1) attenuated CNS transduction relative to that of AAVrh.10.
30894463	2	25	theme	underlying	464:473	arg1	mechanisms					475:484	the underlying mechanisms	460:484	the underlying mechanisms	460:484	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	0	26	theme	Nervous	60:66	arg1	System					68:73	System	68:73	System	68:73	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	11	27	dep	postulate	1689:1697	arg1	influence					1759:1767	influence	1759:1767	can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy	1755:2052	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	11	28	theme	new	1905:1907	arg1	approaches					1909:1918	new approaches	1905:1918	new approaches	1905:1918	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	5	29	theme	relative	842:849	arg1	dependence					855:864	their relative SIA dependence	836:864	their relative SIA dependence	836:864	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	12	30	theme	vascular	2208:2215	arg1	barrier					2217:2223	the vascular barrier	2204:2223	the vascular barrier	2204:2223	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	4	31	theme	SIA-capsid	656:665	arg1	interactions					667:678	altered SIA-capsid interactions	648:678	altered SIA-capsid interactions	648:678	We hypothesized that altered SIA-capsid interactions may influence the ability of AAV1RX to transduce the CNS.
30894463	0	32	theme	Transduction	75:86	arg1	Profile					88:94	the Central Nervous System Transduction Profile	48:94	the Central Nervous System Transduction Profile of Adeno-associated Viruses	48:122	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	2	33	from	footprint	326:334	arg1	capsid					352:357	the AAVrh.10 capsid	339:357	the AAVrh.10 capsid	339:357	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	12	34	theme	viruses	2187:2193	arg1	ability					2164:2170	the ability	2160:2170	the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons	2160:2287	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	12	35	theme	recombinant	2175:2185	arg1	viruses					2187:2193	recombinant viruses	2175:2193	recombinant viruses	2175:2193	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	11	36	theme	Understanding	1824:1836	arg1	profile					1790:1796	the CNS transduction profile	1769:1796	the CNS transduction profile of AAV capsids.IMPORTANCE Understanding	1769:1836	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	0	37	theme	Viruses	116:122	arg1	Profile					88:94	the Central Nervous System Transduction Profile	48:94	the Central Nervous System Transduction Profile of Adeno-associated Viruses	48:122	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	11	38	theme	AAV	1801:1803	arg1	Understanding					1824:1836	AAV capsids.IMPORTANCE Understanding	1801:1836	AAV capsids.IMPORTANCE Understanding	1801:1836	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	5	39	theme	SIA	771:773	arg1	footprints					775:784	altered SIA footprints	763:784	altered SIA footprints	763:784	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	8	40	theme	AAVrh.10	1317:1324	arg1	level					1308:1312	the level	1304:1312	the level of AAVrh.10	1304:1324	The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10.
30894463	0	41	theme	Sialic	14:19	arg1	Dependence					26:35	Sialic Acid Dependence	14:35	Sialic Acid Dependence	14:35	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	0	42	theme	Dependence	26:35	arg1	Modulation					0:9	Modulation	0:9	Modulation of Sialic Acid Dependence	0:35	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	5	43	theme	AAV1	744:747	arg1	variants					749:756	AAV1 variants	744:756	AAV1 variants with altered SIA footprints	744:784	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	10	44	theme	SIA	1618:1620	arg1	interactions					1622:1633	altered SIA interactions	1610:1633	altered SIA interactions playing a partial role in this phenotype	1610:1674	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	7	45	dep	shows	1001:1005	arg1	transduces					1104:1113	transduces	1104:1113	transduces the vasculature and the liver	1104:1143	In contrast, AAV1 shows strong SIA dependency and does not transduce the CNS after systemic administration and, instead, transduces the vasculature and the liver.
30894463	12	46	theme	virus-carbohydrate	2085:2102	arg1	interactions					2104:2115	virus-carbohydrate interactions	2085:2115	virus-carbohydrate interactions	2085:2115	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	10	47	theme	partial	1645:1651	arg1	role					1653:1656	a partial role	1643:1656	a partial role	1643:1656	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	11	48	theme	CNS	1773:1775	arg1	profile					1790:1796	the CNS transduction profile	1769:1796	the CNS transduction profile of AAV capsids.IMPORTANCE Understanding	1769:1836	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	1	49	theme	blood-brain	267:277	arg1	barrier					279:285	the blood-brain barrier	263:285	the blood-brain barrier (BBB)	263:291	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	1	49	theme	blood-brain	267:277	arg1	BBB					288:290	BBB	288:290	BBB	288:290	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	10	50	theme	residues	1502:1509	arg1	composition					1487:1497	the composition	1483:1497	the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10	1483:1572	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	9	51	theme	footprint	1375:1383	arg1	swap					1356:1359	the reciprocal swap	1341:1359	the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1)	1341:1406	In corollary, the reciprocal swap of the AAV1RX footprint onto AAVrh.10 (AAVRX1) attenuated CNS transduction relative to that of AAVrh.10.
30894463	10	52	theme	variable	1529:1536	arg1	region					1538:1543	the capsid variable region 1	1518:1545	the capsid variable region 1 (VR1) of AAV1 and AAVrh.10	1518:1572	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	10	52	theme	variable	1529:1536	arg1	VR1					1548:1550	VR1	1548:1550	VR1	1548:1550	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	5	53	theme	capsids	825:831	arg1	attributes					805:814	functional attributes	794:814	functional attributes of these capsids	794:831	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	7	54	theme	SIA	1014:1016	arg1	dependency					1018:1027	strong SIA dependency	1007:1027	strong SIA dependency	1007:1027	In contrast, AAV1 shows strong SIA dependency and does not transduce the CNS after systemic administration and, instead, transduces the vasculature and the liver.
30894463	1	55	theme	viral	225:229	arg1	vectors					237:243	systemically administered recombinant adeno-associated viral (AAV) vectors	170:243	systemically administered recombinant adeno-associated viral (AAV) vectors	170:243	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	12	56	theme	efficient	2254:2262	arg1	transfer					2269:2276	efficient gene transfer	2254:2276	efficient gene transfer to neurons	2254:2287	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	8	57	theme	SIA	1194:1196	arg1	phenotype					1206:1214	an intermediate SIA binding phenotype	1178:1214	an intermediate SIA binding phenotype	1178:1214	The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10.
30894463	2	58	theme	AAVrh.10	343:350	arg1	capsid					352:357	the AAVrh.10 capsid	339:357	the AAVrh.10 capsid	339:357	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	5	59	theme	functional	794:803	arg1	attributes					805:814	functional attributes	794:814	functional attributes of these capsids	794:831	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	11	60	theme	glycan	1735:1740	arg1	interactions					1742:1753	wherein optimal glycan interactions	1719:1753	wherein optimal glycan interactions	1719:1753	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	1	61	theme	Central	125:131	arg1	system					141:146	Central nervous system	125:146	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors	125:243	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	1	61	theme	Central	125:131	arg1	CNS					149:151	CNS	149:151	CNS	149:151	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	6	62	theme	ablated	894:900	arg1	binding					906:912	ablated SIA binding	894:912	ablated SIA binding	894:912	Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency.
30894463	11	63	theme	viral	2023:2027	arg1	vectors					2029:2035	new recombinant viral vectors	2007:2035	new recombinant viral vectors for gene therapy	2007:2052	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	11	64	theme	wherein	1719:1725	arg1	interactions					1742:1753	wherein optimal glycan interactions	1719:1753	wherein optimal glycan interactions	1719:1753	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	3	65	theme	sialic	590:595	arg1	SIA					603:605	SIA	603:605	SIA	603:605	Here, we establish through structural modeling that this footprint overlaps in part the sialic acid (SIA) footprint on AAV1.
30894463	3	65	theme	sialic	590:595	arg1	acid					597:600	sialic acid	590:600	the sialic acid (SIA) footprint on AAV1	586:624	Here, we establish through structural modeling that this footprint overlaps in part the sialic acid (SIA) footprint on AAV1.
30894463	1	66	theme	system	141:146	arg1	transduction					154:165	Central nervous system (CNS) transduction	125:165	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors	125:243	Central nervous system (CNS) transduction by systemically administered recombinant adeno-associated viral (AAV) vectors requires crossing the blood-brain barrier (BBB).
30894463	11	67	theme	new	2007:2009	arg1	vectors					2029:2035	new recombinant viral vectors	2007:2035	new recombinant viral vectors for gene therapy	2007:2052	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	0	68	theme	System	68:73	arg1	Profile					88:94	the Central Nervous System Transduction Profile	48:94	the Central Nervous System Transduction Profile of Adeno-associated Viruses	48:122	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	5	69	theme	SIA	851:853	arg1	dependence					855:864	their relative SIA dependence	836:864	their relative SIA dependence	836:864	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	6	70	theme	low	955:957	arg1	efficiency					971:980	low to moderate efficiency	955:980	low to moderate efficiency	955:980	Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency.
30894463	6	71	dep	low	955:957	arg1	moderate					962:969	moderate	962:969	moderate	962:969	Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency.
30894463	6	71	dep	low	955:957	arg1	to					959:960	to	959:960	to	959:960	Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency.
30894463	4	72	theme	altered	648:654	arg1	interactions					667:678	altered SIA-capsid interactions	648:678	altered SIA-capsid interactions	648:678	We hypothesized that altered SIA-capsid interactions may influence the ability of AAV1RX to transduce the CNS.
30894463	0	73	theme	Adeno-associated	99:114	arg1	Viruses					116:122	Adeno-associated Viruses	99:122	Adeno-associated Viruses	99:122	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	2	74	dep	enables	411:417	arg1	footprint					326:334	a structural footprint	313:334	a structural footprint	313:334	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	11	75	dep	influence	1759:1767	arg1	provide					1884:1890	provide	1884:1890	can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy	1880:2052	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	8	76	theme	comparable	1290:1299	arg1	levels					1283:1288	levels	1283:1288	levels comparable to the level of AAVrh.10	1283:1324	The AAV1RX variant, which shows an intermediate SIA binding phenotype, effectively enters the brain parenchyma and transduces neurons at levels comparable to the level of AAVrh.10.
30894463	10	77	theme	AAV1	1556:1559	arg1	region					1538:1543	the capsid variable region 1	1518:1545	the capsid variable region 1 (VR1) of AAV1 and AAVrh.10	1518:1572	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	10	77	theme	AAV1	1556:1559	arg1	VR1					1548:1550	VR1	1548:1550	VR1	1548:1550	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	5	78	theme	altered	763:769	arg1	footprints					775:784	altered SIA footprints	763:784	altered SIA footprints	763:784	Using AAV1 variants with altered SIA footprints, we map functional attributes of these capsids to their relative SIA dependence.
30894463	2	79	theme	viral	419:423	arg1	transport					425:433	viral transport	419:433	viral transport across the BBB	419:448	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	12	80	theme	virion	2133:2138	arg1	shell					2140:2144	the virion shell	2129:2144	the virion shell	2129:2144	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	11	81	theme	capsids.IMPORTANCE	1805:1822	arg1	Understanding					1824:1836	AAV capsids.IMPORTANCE Understanding	1801:1836	AAV capsids.IMPORTANCE Understanding	1801:1836	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	0	82	theme	Acid	21:24	arg1	Dependence					26:35	Sialic Acid Dependence	14:35	Sialic Acid Dependence	14:35	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	4	83	theme	AAV1RX	709:714	arg1	ability					698:704	the ability	694:704	the ability of AAV1RX to transduce the CNS	694:735	We hypothesized that altered SIA-capsid interactions may influence the ability of AAV1RX to transduce the CNS.
30894463	11	84	theme	blood-brain	1860:1870	arg1	barrier					1872:1878	the blood-brain barrier	1856:1878	the blood-brain barrier	1856:1878	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	2	85	theme	AAV1	389:392	arg1	AAV1RX					402:407	AAV1RX	402:407	AAV1RX	402:407	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	2	85	theme	AAV1	389:392	arg1	capsid					394:399	the AAV1 capsid	385:399	the AAV1 capsid (AAV1RX)	385:408	We recently mapped a structural footprint on the AAVrh.10 capsid, which, when grafted onto the AAV1 capsid (AAV1RX), enables viral transport across the BBB; however, the underlying mechanisms remain unknown.
30894463	12	86	theme	interactions	2104:2115	arg1	modulation					2071:2080	modulation	2071:2080	modulation of virus-carbohydrate interactions by mutating the virion shell	2071:2144	In this regard, modulation of virus-carbohydrate interactions by mutating the virion shell can influence the ability of recombinant viruses to cross the vascular barrier, enter the brain, and enable efficient gene transfer to neurons.
30894463	10	87	theme	AAVrh.10	1565:1572	arg1	region					1538:1543	the capsid variable region 1	1518:1545	the capsid variable region 1 (VR1) of AAV1 and AAVrh.10	1518:1572	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	10	87	theme	AAVrh.10	1565:1572	arg1	VR1					1548:1550	VR1	1548:1550	VR1	1548:1550	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	0	88	theme	Central	52:58	arg1	System					68:73	System	68:73	System	68:73	Modulation of Sialic Acid Dependence Influences the Central Nervous System Transduction Profile of Adeno-associated Viruses.
30894463	10	89	theme	altered	1610:1616	arg1	interactions					1622:1633	altered SIA interactions	1610:1633	altered SIA interactions playing a partial role in this phenotype	1610:1674	We conclude that the composition of residues within the capsid variable region 1 (VR1) of AAV1 and AAVrh.10 profoundly influences tropism, with altered SIA interactions playing a partial role in this phenotype.
30894463	11	90	dep	viruses	1842:1848	arg1	cross					1850:1854	cross	1850:1854	cross	1850:1854	Further, we postulate a Goldilocks model, wherein optimal glycan interactions can influence the CNS transduction profile of AAV capsids.IMPORTANCE Understanding how viruses cross the blood-brain barrier can provide insight into new approaches to block infection by pathogens or the ability to exploit these pathways for designing new recombinant viral vectors for gene therapy.
30894463	6	91	with	capsids	881:887	arg1	binding					906:912	ablated SIA binding	894:912	ablated SIA binding	894:912	Specifically, capsids with ablated SIA binding can penetrate and transduce the CNS with low to moderate efficiency.
30743061	12	0	dep	cells	1556:1560	arg1	i.e.					1531:1534	i.e.	1531:1534	i.e.	1531:1534	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	12	1	theme	EPS	1378:1380	arg1	analysis					1382:1389	EPS analysis	1378:1389	EPS analysis	1378:1389	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	4	2	theme	polymeric	652:660	arg1	EPS					674:676	EPS	674:676	EPS	674:676	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	4	2	theme	polymeric	652:660	arg1	substances					662:671	extracellular polymeric substances	638:671	extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments	638:735	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	2	3	theme	reactor	270:276	arg1	leaching					278:285	reactor leaching	270:285	reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps	270:361	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	5	4	theme	thermoacidophilic	857:873	arg1	archaeon					875:882	the thermoacidophilic archaeon	853:882	the thermoacidophilic archaeon Acidianus sp	853:895	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	12	5	theme	uronic	1447:1452	arg1	acids					1454:1458	uronic acids	1447:1458	uronic acids	1447:1458	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	3	6	theme	thermoacidophilic	544:560	arg1	archaea					562:568	thermoacidophilic archaea	544:568	thermoacidophilic archaea	544:568	Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite.
30743061	5	7	theme	Acidianus	884:892	arg1	sp					894:895	the thermoacidophilic archaeon Acidianus sp	853:895	the thermoacidophilic archaeon Acidianus sp	853:895	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	2	8	theme	temperature	294:304	arg1	range					306:310	the temperature range	290:310	the temperature range of 50 up to 90 °C	290:328	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	5	9	theme	EPS	835:837	arg1	production					839:848	EPS production	835:848	EPS production of the thermoacidophilic archaeon Acidianus sp	835:895	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	13	10	theme	extreme	1742:1748	arg1	environments					1750:1761	extreme environments	1742:1761	extreme environments	1742:1761	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	3	11	theme	natural	580:586	arg1	substrates					596:605	their natural mineral substrates	574:605	their natural mineral substrates such as pyrite	574:620	Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite.
30743061	3	11	theme	natural	580:586	arg1	pyrite					615:620	pyrite	615:620	pyrite	615:620	Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite.
30743061	5	12	theme	biofilm	814:820	arg1	dynamics					822:829	biofilm dynamics	814:829	biofilm dynamics	814:829	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	1	13	theme	interfacial	125:135	arg1	process					137:143	an interfacial process	122:143	an interfacial process where biofilm formation is important in the initial steps of this process	122:217	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	2	14	from	leaching	278:285	arg1	range					306:310	the temperature range	290:310	the temperature range of 50 up to 90 °C	290:328	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	2	14	from	leaching	278:285	arg1	heaps					357:361	(self-heating) heaps	342:361	(self-heating) heaps	342:361	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	14	15	theme	thermophilic	1879:1890	arg1	bioleaching					1892:1902	thermophilic bioleaching	1879:1902	thermophilic bioleaching	1879:1902	Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.
30743061	0	16	theme	bioleaching	59:69	arg1	archaeon					71:78	a thermoacidophilic bioleaching archaeon	39:78	a thermoacidophilic bioleaching archaeon	39:78	Biofilm dynamics and EPS production of a thermoacidophilic bioleaching archaeon.
30743061	13	17	from	environments	1750:1761	arg1	understanding					1667:1679	understanding	1667:1679	understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments	1667:1761	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	2	18	theme	bioleaching	249:259	arg1	applications					233:244	technical applications	223:244	technical applications	223:244	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	2	18	theme	bioleaching	249:259	arg1	leaching					278:285	reactor leaching	270:285	reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps	270:361	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	12	19	theme	planktonic	1536:1545	arg1	cells					1556:1560	planktonic, biofilm cells	1536:1560	planktonic, biofilm cells	1536:1560	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	12	19	theme	planktonic	1536:1545	arg1	substrate					1506:1514	substrate	1506:1514	substrate	1506:1514	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	4	20	theme	archaea	682:688	arg1	EPS					674:676	EPS	674:676	EPS	674:676	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	4	20	theme	archaea	682:688	arg1	substances					662:671	extracellular polymeric substances	638:671	extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments	638:735	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	8	21	theme	surfaces	1038:1045	arg1	parts					1018:1022	Large parts	1012:1022	Large parts of the pyrite surfaces	1012:1045	Large parts of the pyrite surfaces remain free of cells.
30743061	13	22	theme	interfacial	1714:1724	arg1	interactions					1726:1737	the mineral-microbial-biofilm interfacial interactions	1684:1737	the mineral-microbial-biofilm interfacial interactions in extreme environments	1684:1761	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	2	23	theme	thermophilic	364:375	arg1	archaea					377:383	thermophilic archaea	364:383	thermophilic archaea	364:383	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	8	24	theme	cells	1062:1066	arg1	free					1054:1057	free	1054:1057	free	1054:1057	Large parts of the pyrite surfaces remain free of cells.
30743061	0	25	theme	Biofilm	0:6	arg1	dynamics					8:15	Biofilm dynamics	0:15	Biofilm dynamics	0:15	Biofilm dynamics and EPS production of a thermoacidophilic bioleaching archaeon.
30743061	13	26	from	understanding	1667:1679	arg1	environments					1750:1761	extreme environments	1742:1761	extreme environments	1742:1761	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	1	27	theme	metal	96:100	arg1	sulfides					102:109	metal sulfides	96:109	metal sulfides	96:109	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	2	28	theme	important	393:401	arg1	role					403:406	an important role	390:406	an important role	390:406	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	5	29	theme	dynamics	822:829	arg1	production					839:848	EPS production	835:848	EPS production of the thermoacidophilic archaeon Acidianus sp	835:895	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	5	29	theme	dynamics	822:829	arg1	investigations					796:809	investigations	796:809	investigations of biofilm dynamics	796:829	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	14	30	theme	microbial	1822:1830	arg1	consortia					1832:1840	archaeal microbial consortia	1813:1840	archaeal microbial consortia	1813:1840	Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.
30743061	5	31	theme	sp	894:895	arg1	production					839:848	EPS production	835:848	EPS production of the thermoacidophilic archaeon Acidianus sp	835:895	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	5	31	theme	sp	894:895	arg1	investigations					796:809	investigations	796:809	investigations of biofilm dynamics	796:829	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	13	32	theme	thermophilic	1633:1644	arg1	archaea					1646:1652	thermophilic archaea	1633:1652	thermophilic archaea	1633:1652	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	10	33	theme	incubation	1288:1297	arg1	days					1280:1283	2-4 days	1276:1283	2-4 days of incubation	1276:1297	A monolayer biofilm develops on pyrite after 2-4 days of incubation.
30743061	5	34	theme	archaeon	875:882	arg1	sp					894:895	the thermoacidophilic archaeon Acidianus sp	853:895	the thermoacidophilic archaeon Acidianus sp	853:895	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	2	35	theme	leaching	426:433	arg1	organisms					435:443	the leaching organisms	422:443	the leaching organisms of choice	422:453	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	14	36	theme	interaction	1789:1799	arg1	dynamics					1801:1808	interaction dynamics	1789:1808	interaction dynamics of archaeal microbial consortia	1789:1840	Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.
30743061	12	37	dep	planktonic	1536:1545	arg1	biofilm					1548:1554	biofilm	1548:1554	biofilm	1548:1554	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	11	38	theme	organic	1359:1365	arg1	compounds					1367:1375	organic compounds	1359:1375	organic compounds	1359:1375	In addition, the pyrite surface is covered with a layer of organic compounds.
30743061	9	39	theme	binding	1154:1160	arg1	assays					1162:1167	lectin binding assays	1147:1167	lectin binding assays	1147:1167	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
30743061	2	40	theme	self-heating	343:354	arg1	heaps					357:361	(self-heating) heaps	342:361	(self-heating) heaps	342:361	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	12	41	theme	polysaccharides	1427:1441	arg1	presence					1405:1412	the presence	1401:1412	the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells)	1401:1561	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	9	42	contain	containing	1209:1218	arg1	mannose					1181:1187	mannose	1181:1187	mannose	1181:1187	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
30743061	9	42	contain	containing	1209:1218	arg2	compounds					1220:1228	compounds	1220:1228	compounds	1220:1228	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
30743061	6	43	theme	bioleaching	914:924	arg1	conditions					926:935	bioleaching conditions	914:935	bioleaching conditions	914:935	DSM 29099 under bioleaching conditions.
30743061	3	44	theme	available	506:514	arg1	information					494:504	little information	487:504	little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite	487:620	Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite.
30743061	8	45	theme	Large	1012:1016	arg1	parts					1018:1022	Large parts	1012:1022	Large parts of the pyrite surfaces	1012:1045	Large parts of the pyrite surfaces remain free of cells.
30743061	3	46	theme	little	487:492	arg1	information					494:504	little information	487:504	little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite	487:620	Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite.
30743061	4	47	from	substances	662:671	arg1	environments					724:735	bioleaching environments	712:735	bioleaching environments	712:735	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	12	48	theme	proteins	1417:1424	arg1	presence					1405:1412	the presence	1401:1412	the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells)	1401:1561	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	4	49	theme	extracellular	638:650	arg1	EPS					674:676	EPS	674:676	EPS	674:676	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	4	49	theme	extracellular	638:650	arg1	substances					662:671	extracellular polymeric substances	638:671	extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments	638:735	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	11	50	theme	pyrite	1317:1322	arg1	surface					1324:1330	the pyrite surface	1313:1330	the pyrite surface	1313:1330	In addition, the pyrite surface is covered with a layer of organic compounds.
30743061	1	51	theme	initial	189:195	arg1	steps					197:201	the initial steps	185:201	the initial steps of this process	185:217	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	8	52	theme	pyrite	1031:1036	arg1	surfaces					1038:1045	the pyrite surfaces	1027:1045	the pyrite surfaces	1027:1045	Large parts of the pyrite surfaces remain free of cells.
30743061	1	53	theme	process	211:217	arg1	steps					197:201	the initial steps	185:201	the initial steps of this process	185:217	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	2	54	theme	technical	223:231	arg1	applications					233:244	technical applications	223:244	technical applications	223:244	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	2	54	theme	technical	223:231	arg1	leaching					278:285	reactor leaching	270:285	reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps	270:361	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	10	55	theme	monolayer	1233:1241	arg1	biofilm					1243:1249	A monolayer biofilm	1231:1249	A monolayer biofilm	1231:1249	A monolayer biofilm develops on pyrite after 2-4 days of incubation.
30743061	14	56	theme	bioleaching	1892:1902	arg1	understanding					1862:1874	the understanding	1858:1874	the understanding of thermophilic bioleaching	1858:1902	Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.
30743061	4	57	theme	biofilms	700:707	arg1	EPS					674:676	EPS	674:676	EPS	674:676	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	4	57	theme	biofilms	700:707	arg1	substances					662:671	extracellular polymeric substances	638:671	extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments	638:735	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	0	58	theme	archaeon	71:78	arg1	dynamics					8:15	Biofilm dynamics	0:15	Biofilm dynamics	0:15	Biofilm dynamics and EPS production of a thermoacidophilic bioleaching archaeon.
30743061	0	58	theme	archaeon	71:78	arg1	production					25:34	EPS production	21:34	EPS production of a thermoacidophilic bioleaching archaeon	21:78	Biofilm dynamics and EPS production of a thermoacidophilic bioleaching archaeon.
30743061	3	59	theme	mineral	588:594	arg1	substrates					596:605	their natural mineral substrates	574:605	their natural mineral substrates such as pyrite	574:620	Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite.
30743061	3	59	theme	mineral	588:594	arg1	pyrite					615:620	pyrite	615:620	pyrite	615:620	Nevertheless, to date there is little information available on the interactions between thermoacidophilic archaea and their natural mineral substrates such as pyrite.
30743061	1	60	from	steps	197:201	arg1	important					172:180	important	172:180	important	172:180	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	1	61	theme	biofilm	151:157	arg1	formation					159:167	biofilm formation	151:167	biofilm formation	151:167	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	14	62	from	results	1778:1784	arg1	dynamics					1801:1808	interaction dynamics	1789:1808	interaction dynamics of archaeal microbial consortia	1789:1840	Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.
30743061	2	63	theme	choice	448:453	arg1	organisms					435:443	the leaching organisms	422:443	the leaching organisms of choice	422:453	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	13	64	theme	mineral-microbial-biofilm	1688:1712	arg1	interactions					1726:1737	the mineral-microbial-biofilm interfacial interactions	1684:1737	the mineral-microbial-biofilm interfacial interactions in extreme environments	1684:1761	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	9	65	theme	Cell	1069:1072	arg1	detachment					1074:1083	Cell detachment	1069:1083	Cell detachment from pyrite	1069:1095	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
30743061	1	66	from	important	172:180	arg1	steps					197:201	the initial steps	185:201	the initial steps of this process	185:217	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	13	67	theme	interactions	1726:1737	arg1	understanding					1667:1679	understanding	1667:1679	understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments	1667:1761	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	4	68	theme	bioleaching	712:722	arg1	environments					724:735	bioleaching environments	712:735	bioleaching environments	712:735	Especially for extracellular polymeric substances (EPS) of archaea and their biofilms in bioleaching environments information is rather limited.
30743061	9	69	theme	microbial	1108:1116	arg1	"					1129:1129	microbial "footprints"	1108:1129	microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds	1108:1228	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
30743061	0	70	theme	EPS	21:23	arg1	production					25:34	EPS production	21:34	EPS production of a thermoacidophilic bioleaching archaeon	21:78	Biofilm dynamics and EPS production of a thermoacidophilic bioleaching archaeon.
30743061	14	71	theme	consortia	1832:1840	arg1	dynamics					1801:1808	interaction dynamics	1789:1808	interaction dynamics of archaeal microbial consortia	1789:1840	Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.
30743061	1	72	theme	sulfides	102:109	arg1	Bioleaching					81:91	Bioleaching	81:91	Bioleaching of metal sulfides	81:109	Bioleaching of metal sulfides represents an interfacial process where biofilm formation is important in the initial steps of this process.
30743061	9	73	theme	footprints	1119:1128	arg1	"					1129:1129	microbial "footprints"	1108:1129	microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds	1108:1228	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
30743061	5	74	theme	present	772:778	arg1	work					780:783	The present work	768:783	The present work	768:783	The present work focused on investigations of biofilm dynamics and EPS production of the thermoacidophilic archaeon Acidianus sp.
30743061	14	75	theme	archaeal	1813:1820	arg1	consortia					1832:1840	archaeal microbial consortia	1813:1840	archaeal microbial consortia	1813:1840	Moreover, the results on interaction dynamics of archaeal microbial consortia will facilitate the understanding of thermophilic bioleaching.
30743061	13	76	theme	archaea	1646:1652	arg1	characteristics					1614:1628	EPS and biofilm characteristics	1598:1628	EPS and biofilm characteristics of thermophilic archaea	1598:1652	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	0	77	theme	thermoacidophilic	41:57	arg1	archaeon					71:78	a thermoacidophilic bioleaching archaeon	39:78	a thermoacidophilic bioleaching archaeon	39:78	Biofilm dynamics and EPS production of a thermoacidophilic bioleaching archaeon.
30743061	13	78	from	interactions	1726:1737	arg1	environments					1750:1761	extreme environments	1742:1761	extreme environments	1742:1761	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	13	79	theme	EPS	1598:1600	arg1	characteristics					1614:1628	EPS and biofilm characteristics	1598:1628	EPS and biofilm characteristics of thermophilic archaea	1598:1652	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	12	80	theme	acids	1454:1458	arg1	composition					1465:1475	the composition	1461:1475	the composition	1461:1475	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	12	80	theme	acids	1454:1458	arg1	presence					1405:1412	the presence	1401:1412	the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells)	1401:1561	EPS analysis indicates the presence of proteins, polysaccharides and uronic acids, the composition of which varies according to substrate and lifestyle (i.e. planktonic, biofilm cells).
30743061	13	81	theme	biofilm	1606:1612	arg1	characteristics					1614:1628	EPS and biofilm characteristics	1598:1628	EPS and biofilm characteristics of thermophilic archaea	1598:1652	This report provides insight into EPS and biofilm characteristics of thermophilic archaea and improves understanding of the mineral-microbial-biofilm interfacial interactions in extreme environments.
30743061	9	82	theme	lectin	1147:1152	arg1	assays					1162:1167	lectin binding assays	1147:1167	lectin binding assays	1147:1167	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
30743061	2	83	theme	up	318:319	arg1	range					306:310	the temperature range	290:310	the temperature range of 50 up to 90 °C	290:328	In technical applications of bioleaching, such as reactor leaching in the temperature range of 50 up to 90 °C and also in (self-heating) heaps, thermophilic archaea play an important role and often are the leaching organisms of choice.
30743061	11	84	theme	compounds	1367:1375	arg1	layer					1350:1354	a layer	1348:1354	a layer of organic compounds	1348:1375	In addition, the pyrite surface is covered with a layer of organic compounds.
30743061	9	85	from	pyrite	1090:1095	arg1	detachment					1074:1083	Cell detachment	1069:1083	Cell detachment from pyrite	1069:1095	Cell detachment from pyrite results in microbial "footprints" which, based on lectin binding assays, consist of mannose, glucose and fucose containing compounds.
31790925	2	0	dep	in	529:530	arg1	vitro					532:536	vitro	532:536	vitro	532:536	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	3	1	theme	benzyl	1028:1033	arg1	BA					1044:1045	BA	1044:1045	BA	1044:1045	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	1	theme	benzyl	1028:1033	arg1	adenine					1035:1041	benzyl adenine	1028:1041	benzyl adenine (BA)	1028:1046	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	10	2	theme	goji	2124:2127	arg1	metabolites					2139:2149	goji secondary metabolites	2124:2149	goji secondary metabolites	2124:2149	The culture protocol described in this paper could be employed for the development of novel methods for the commercial production of goji secondary metabolites.
31790925	0	3	from	profiles	146:153	arg1	calli					158:162	calli	158:162	calli	158:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	3	4	theme	NAA	1052:1054	arg1	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	4	theme	NAA	1052:1054	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	2	5	theme	culture	538:544	arg1	protocols					546:554	in vitro culture protocols	529:554	in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants	529:637	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	3	6	theme	PGRs	933:936	arg1	TDZ					952:954	TDZ	952:954	TDZ	952:954	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	6	theme	PGRs	933:936	arg1	[thidiazuron					938:949	PGRs [thidiazuron	933:949	PGRs [thidiazuron (TDZ)	933:955	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	9	7	theme	berry	1984:1988	arg1	callus					1969:1974	the callus	1965:1974	the callus of goji berry	1965:1988	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	8	8	theme	TDZ/NAA	1695:1701	arg1	combination					1703:1713	TDZ/NAA combination	1695:1713	TDZ/NAA combination	1695:1713	The TDZ/IAA combination, TDZ alone, and TDZ/NAA combination significantly increased vanillic acid and rutin, gallic acid, and quercetin synthesis, respectively.
31790925	2	9	theme	plant	581:585	arg1	regeneration					587:598	plant regeneration	581:598	plant regeneration	581:598	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	7	10	theme	acid	1632:1635	arg1	accumulation					1604:1615	accumulation	1604:1615	accumulation	1604:1615	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	7	10	theme	acid	1632:1635	arg1	production					1589:1598	production	1589:1598	production	1589:1598	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	0	11	theme	different	177:185	arg1	combinations					187:198	different combinations	177:198	different combinations of plant growth regulators	177:225	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	6	12	from	different	1451:1459	arg1	callus					1468:1473	the callus	1464:1473	the callus obtained from different PGRs or combinations	1464:1518	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	10	13	theme	metabolites	2139:2149	arg1	production					2110:2119	the commercial production	2095:2119	the commercial production of goji secondary metabolites	2095:2149	The culture protocol described in this paper could be employed for the development of novel methods for the commercial production of goji secondary metabolites.
31790925	2	14	theme	different	691:699	arg1	origin					701:706	different origin	691:706	different origin	691:706	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	4	15	theme	nodal	1192:1196	arg1	explants					1198:1205	nodal explants	1192:1205	nodal explants	1192:1205	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	8	16	theme	vanillic	1739:1746	arg1	acid					1748:1751	vanillic acid	1739:1751	vanillic acid	1739:1751	The TDZ/IAA combination, TDZ alone, and TDZ/NAA combination significantly increased vanillic acid and rutin, gallic acid, and quercetin synthesis, respectively.
31790925	1	17	theme	dietary	425:431	arg1	phenolics					454:462	phenolics	454:462	phenolics	454:462	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	17	theme	dietary	425:431	arg1	carotenoids					475:485	carotenoids	475:485	carotenoids	475:485	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	17	theme	dietary	425:431	arg1	polysaccharides					492:506	polysaccharides	492:506	polysaccharides	492:506	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	17	theme	dietary	425:431	arg1	vitamins					465:472	vitamins	465:472	vitamins	465:472	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	17	theme	dietary	425:431	arg1	constituents					433:444	several dietary constituents	417:444	several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides	417:506	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	18	contain	has	276:278	arg2	effects					296:302	many beneficial effects	280:302	many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health	280:404	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	18	contain	has	276:278	arg1	fruit					265:269	a fruit	263:269	a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides	263:506	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	18	contain	has	276:278	arg1	berry					233:237	berry	233:237	berry	233:237	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	10	19	theme	methods	2083:2089	arg1	development					2062:2072	the development	2058:2072	the development of novel methods for the commercial production of goji secondary metabolites	2058:2149	The culture protocol described in this paper could be employed for the development of novel methods for the commercial production of goji secondary metabolites.
31790925	2	20	theme	plant	733:737	arg1	PGRs					758:761	PGRs	758:761	PGRs	758:761	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	2	20	theme	plant	733:737	arg1	regulators					746:755	plant growth regulators	733:755	plant growth regulators (PGRs)	733:762	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	0	21	from	explants	75:82	arg1	regeneration					16:27	Efficient plant regeneration	0:27	Efficient plant regeneration	0:27	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	21	from	explants	75:82	arg1	induction					40:48	callus induction	33:48	callus induction	33:48	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	21	from	explants	75:82	arg1	comparison					123:132	comparison	123:132	comparison of phenolic profiles in calli	123:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	6	22	theme	selected	1403:1410	arg1	substances					1421:1430	selected phenolic substances	1403:1430	selected phenolic substances	1403:1430	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	2	23	theme	in	529:530	arg1	protocols					546:554	in vitro culture protocols	529:554	in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants	529:637	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	8	24	theme	quercetin	1781:1789	arg1	synthesis					1791:1799	quercetin synthesis	1781:1799	quercetin synthesis	1781:1799	The TDZ/IAA combination, TDZ alone, and TDZ/NAA combination significantly increased vanillic acid and rutin, gallic acid, and quercetin synthesis, respectively.
31790925	3	25	theme	explants	795:802	arg1	types					786:790	Various types	778:790	Various types of explants (leaf, petiole, root, hypocotyl, and node)	778:845	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	10	26	theme	novel	2077:2081	arg1	methods					2083:2089	novel methods	2077:2089	novel methods for the commercial production of goji secondary metabolites	2077:2149	The culture protocol described in this paper could be employed for the development of novel methods for the commercial production of goji secondary metabolites.
31790925	6	27	theme	different	1489:1497	arg1	PGRs					1499:1502	different PGRs	1489:1502	different PGRs	1489:1502	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	7	28	theme	caffeic	1641:1647	arg1	acid					1649:1652	caffeic acid	1641:1652	caffeic acid	1641:1652	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	2	29	from	explants	615:622	arg1	protocols					546:554	in vitro culture protocols	529:554	in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants	529:637	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	0	30	theme	phenolic	137:144	arg1	profiles					146:153	phenolic profiles	137:153	phenolic profiles in calli	137:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	7	31	theme	BA/NAA	1554:1559	arg1	combination					1539:1549	The combination	1535:1549	The combination of BA/NAA	1535:1559	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	1	32	theme	beneficial	285:294	arg1	effects					296:302	many beneficial effects	280:302	many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health	280:404	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	0	33	from	regeneration	16:27	arg1	calli					158:162	calli	158:162	calli	158:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	3	34	theme	acid	980:983	arg1	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	34	theme	acid	980:983	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	0	35	theme	regulators	216:225	arg1	combinations					187:198	different combinations	177:198	different combinations of plant growth regulators	177:225	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	9	36	theme	kinds	1896:1900	arg1	production					1872:1881	the production	1868:1881	the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry	1868:1988	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	5	37	theme	hypocotyl	1298:1306	arg1	explants					1308:1315	hypocotyl explants	1298:1315	hypocotyl explants	1298:1315	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	2	38	theme	different	605:613	arg1	explants					615:622	different explants	605:622	different explants of Goji plants	605:637	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	3	39	theme	naphthalene	961:971	arg1	NAA					986:988	NAA	986:988	NAA	986:988	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	39	theme	naphthalene	961:971	arg1	acid					980:983	naphthalene acetic acid	961:983	naphthalene acetic acid (NAA)	961:989	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	40	dep	explants	795:802	arg1	node					841:844	node	841:844	node	841:844	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	40	dep	explants	795:802	arg1	explants					795:802	explants	795:802	explants (leaf, petiole, root, hypocotyl, and node)	795:845	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	40	dep	explants	795:802	arg1	root					820:823	root	820:823	root	820:823	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	40	dep	explants	795:802	arg1	hypocotyl					826:834	hypocotyl	826:834	hypocotyl	826:834	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	40	dep	explants	795:802	arg1	leaf					805:808	leaf	805:808	leaf	805:808	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	40	dep	explants	795:802	arg1	petiole					811:817	petiole	811:817	petiole	811:817	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	5	41	theme	mean	1259:1262	arg1	diameter					1271:1278	The highest mean callus diameter	1247:1278	The highest mean callus diameter	1247:1278	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	2	42	theme	plants	632:637	arg1	explants					615:622	different explants	605:622	different explants of Goji plants	605:637	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	0	43	theme	Efficient	0:8	arg1	regeneration					16:27	Efficient plant regeneration	0:27	Efficient plant regeneration	0:27	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	6	44	theme	substances	1421:1430	arg1	amounts					1392:1398	The amounts	1388:1398	The amounts of selected phenolic substances	1388:1430	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	6	44	theme	substances	1421:1430	arg1	substances					1421:1430	selected phenolic substances	1403:1430	selected phenolic substances	1403:1430	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	6	44	theme	substances	1421:1430	arg1	different					1451:1459	different	1451:1459	different	1451:1459	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	9	45	theme	different	1886:1894	arg1	kinds					1896:1900	different kinds	1886:1900	different kinds of secondary metabolites and affect/accelerate accumulation	1886:1960	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	1	46	dep	effects	296:302	arg1	such					305:308	such	305:308	such	305:308	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	5	47	theme	0.1 mg/l	1356:1363	arg1	21.40 ± 0.71 mm					1370:1384	21.40 ± 0.71 mm	1370:1384	21.40 ± 0.71 mm	1370:1384	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	5	47	theme	0.1 mg/l	1356:1363	arg1	IAA					1365:1367	0.1 mg/l IAA	1356:1367	0.1 mg/l IAA (21.40 ± 0.71 mm)	1356:1385	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	0	48	theme	callus	33:38	arg1	induction					40:48	callus induction	33:48	callus induction	33:48	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	3	49	theme	MS	864:865	arg1	medium					867:872	MS medium	864:872	MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA]	864:1080	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	9	50	theme	metabolites	1915:1925	arg1	kinds					1896:1900	different kinds	1886:1900	different kinds of secondary metabolites and affect/accelerate accumulation	1886:1960	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	1	51	from	effects	296:302	arg1	health					399:404	human health	393:404	human health	393:404	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	9	52	theme	affect/accelerate	1931:1947	arg1	accumulation					1949:1960	affect/accelerate accumulation	1931:1960	affect/accelerate accumulation	1931:1960	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	3	53	theme	different	888:896	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	9	54	from	production	1872:1881	arg1	callus					1969:1974	the callus	1965:1974	the callus of goji berry	1965:1988	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	4	55	theme	mean	1095:1098	arg1	number					1100:1105	The highest mean number	1083:1105	The highest mean number of shoots (23.33 ± 1.86)	1083:1130	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	7	56	theme	acid	1649:1652	arg1	accumulation					1604:1615	accumulation	1604:1615	accumulation	1604:1615	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	7	56	theme	acid	1649:1652	arg1	production					1589:1598	production	1589:1598	production	1589:1598	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	7	57	dep	production	1589:1598	arg1	the					1585:1587	the	1585:1587	the	1585:1587	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	4	58	theme	shoot	1150:1154	arg1	formation					1156:1164	shoot formation	1150:1164	shoot formation	1150:1164	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	3	59	theme	adenine	1035:1041	arg1	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	59	theme	adenine	1035:1041	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	9	60	theme	goji	1979:1982	arg1	berry					1984:1988	goji berry	1979:1988	goji berry	1979:1988	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	1	61	theme	human	393:397	arg1	health					399:404	human health	393:404	human health	393:404	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	10	62	theme	commercial	2099:2108	arg1	production					2110:2119	the commercial production	2095:2119	the commercial production of goji secondary metabolites	2095:2149	The culture protocol described in this paper could be employed for the development of novel methods for the commercial production of goji secondary metabolites.
31790925	7	63	theme	chlorogenic	1620:1630	arg1	acid					1632:1635	chlorogenic acid	1620:1635	chlorogenic acid	1620:1635	The combination of BA/NAA significantly increased the production and accumulation of chlorogenic acid and caffeic acid.
31790925	2	64	theme	various	709:715	arg1	combinations					717:728	various combinations	709:728	various combinations of plant growth regulators (PGRs)	709:762	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	0	65	from	comparison	123:132	arg1	calli					158:162	calli	158:162	calli	158:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	5	66	theme	highest	1251:1257	arg1	diameter					1271:1278	The highest mean callus diameter	1247:1278	The highest mean callus diameter	1247:1278	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	2	67	theme	origin	701:706	arg1	calli					682:686	calli	682:686	calli of different origin	682:706	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	0	68	theme	plant	203:207	arg1	regulators					216:225	plant growth regulators	203:225	plant growth regulators	203:225	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	1	69	theme	several	417:423	arg1	phenolics					454:462	phenolics	454:462	phenolics	454:462	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	69	theme	several	417:423	arg1	carotenoids					475:485	carotenoids	475:485	carotenoids	475:485	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	69	theme	several	417:423	arg1	polysaccharides					492:506	polysaccharides	492:506	polysaccharides	492:506	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	69	theme	several	417:423	arg1	vitamins					465:472	vitamins	465:472	vitamins	465:472	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	1	69	theme	several	417:423	arg1	constituents					433:444	several dietary constituents	417:444	several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides	417:506	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	6	70	from	callus	1468:1473	arg1	amounts					1392:1398	The amounts	1388:1398	The amounts of selected phenolic substances	1388:1430	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	6	70	from	callus	1468:1473	arg1	substances					1421:1430	selected phenolic substances	1403:1430	selected phenolic substances	1403:1430	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	6	70	from	callus	1468:1473	arg1	different					1451:1459	different	1451:1459	different	1451:1459	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	2	71	theme	callus	560:565	arg1	induction					567:575	callus induction	560:575	callus induction	560:575	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	3	72	theme	[thidiazuron	938:949	arg1	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	72	theme	[thidiazuron	938:949	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	2	73	theme	growth	739:744	arg1	PGRs					758:761	PGRs	758:761	PGRs	758:761	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	2	73	theme	growth	739:744	arg1	regulators					746:755	plant growth regulators	733:755	plant growth regulators (PGRs)	733:762	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	3	74	theme	TDZ	1063:1065	arg1	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	74	theme	TDZ	1063:1065	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	2	75	from	composition	667:677	arg1	calli					682:686	calli	682:686	calli of different origin	682:706	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	8	76	theme	gallic	1764:1769	arg1	acid					1771:1774	gallic acid	1764:1774	gallic acid	1764:1774	The TDZ/IAA combination, TDZ alone, and TDZ/NAA combination significantly increased vanillic acid and rutin, gallic acid, and quercetin synthesis, respectively.
31790925	2	77	theme	phenolic	658:665	arg1	composition					667:677	the phenolic composition	654:677	the phenolic composition in calli of different origin	654:706	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	5	78	contain	containing	1327:1336	arg2	IAA					1365:1367	0.1 mg/l IAA	1356:1367	0.1 mg/l IAA (21.40 ± 0.71 mm)	1356:1385	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	5	78	contain	containing	1327:1336	arg1	medium					1320:1325	medium	1320:1325	medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm)	1320:1385	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	5	78	contain	containing	1327:1336	arg2	21.40 ± 0.71 mm					1370:1384	21.40 ± 0.71 mm	1370:1384	21.40 ± 0.71 mm	1370:1384	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	5	78	contain	containing	1327:1336	arg2	TDZ					1348:1350	0.25 mg/l TDZ	1338:1350	0.25 mg/l TDZ	1338:1350	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	3	79	theme	BA	1078:1079	arg1	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	79	theme	BA	1078:1079	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	1	80	dep	Lycium	240:245	arg1	L.					256:257	Lycium barbarum L.	240:257	Lycium barbarum L.	240:257	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	0	81	theme	profiles	146:153	arg1	regeneration					16:27	Efficient plant regeneration	0:27	Efficient plant regeneration	0:27	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	81	theme	profiles	146:153	arg1	induction					40:48	callus induction	33:48	callus induction	33:48	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	81	theme	profiles	146:153	arg1	comparison					123:132	comparison	123:132	comparison of phenolic profiles in calli	123:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	10	82	theme	culture	1995:2001	arg1	protocol					2003:2010	The culture protocol	1991:2010	The culture protocol described in this paper	1991:2034	The culture protocol described in this paper could be employed for the development of novel methods for the commercial production of goji secondary metabolites.
31790925	0	83	theme	hypocotyl	65:73	arg1	explants					75:82	nodal and hypocotyl explants	55:82	explants	75:82	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	3	84	contain	containing	874:883	arg2	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	84	contain	containing	874:883	arg1	medium					867:872	MS medium	864:872	MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA]	864:1080	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	84	contain	containing	874:883	arg2	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	85	theme	acetic	973:978	arg1	NAA					986:988	NAA	986:988	NAA	986:988	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	85	theme	acetic	973:978	arg1	acid					980:983	naphthalene acetic acid	961:983	naphthalene acetic acid (NAA)	961:989	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	9	86	theme	different	1845:1853	arg1	PGRs					1855:1858	different PGRs	1845:1858	different PGRs	1845:1858	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	3	87	theme	Various	778:784	arg1	types					786:790	Various types	778:790	Various types of explants (leaf, petiole, root, hypocotyl, and node)	778:845	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	0	88	theme	berry	92:96	arg1	explants					75:82	nodal and hypocotyl explants	55:82	explants	75:82	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	89	theme	growth	209:214	arg1	regulators					216:225	plant growth regulators	203:225	plant growth regulators	203:225	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	90	dep	Lycium	99:104	arg1	L.					115:116	Lycium barbarum L.	99:116	Lycium barbarum L.	99:116	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	4	91	theme	0.5 mg/l	1228:1235	arg1	BA					1237:1238	0.5 mg/l BA	1228:1238	0.5 mg/l BA alone	1228:1244	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	0	92	from	induction	40:48	arg1	calli					158:162	calli	158:162	calli	158:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	5	93	theme	callus	1264:1269	arg1	diameter					1271:1278	The highest mean callus diameter	1247:1278	The highest mean callus diameter	1247:1278	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	0	94	theme	plant	10:14	arg1	regeneration					16:27	Efficient plant regeneration	0:27	Efficient plant regeneration	0:27	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	2	95	theme	Goji	627:630	arg1	plants					632:637	Goji plants	627:637	Goji plants	627:637	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	3	96	theme	indole-3-acetic	1000:1014	arg1	IAA					1022:1024	IAA	1022:1024	IAA	1022:1024	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	96	theme	indole-3-acetic	1000:1014	arg1	acid					1016:1019	indole-3-acetic acid	1000:1019	indole-3-acetic acid (IAA)	1000:1025	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	6	97	theme	phenolic	1412:1419	arg1	substances					1421:1430	selected phenolic substances	1403:1430	selected phenolic substances	1403:1430	The amounts of selected phenolic substances were significantly different in the callus obtained from different PGRs or combinations, individually.
31790925	0	98	from	calli	158:162	arg1	regeneration					16:27	Efficient plant regeneration	0:27	Efficient plant regeneration	0:27	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	98	from	calli	158:162	arg1	induction					40:48	callus induction	33:48	callus induction	33:48	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	0	98	from	calli	158:162	arg1	comparison					123:132	comparison	123:132	comparison of phenolic profiles in calli	123:162	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	4	99	theme	shoots	1110:1115	arg1	percentage					1136:1145	percentage	1136:1145	percentage of shoot formation (100%)	1136:1171	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	4	99	theme	shoots	1110:1115	arg1	%					1170:1170	100%	1167:1170	100%	1167:1170	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	4	99	theme	shoots	1110:1115	arg1	number					1100:1105	The highest mean number	1083:1105	The highest mean number of shoots (23.33 ± 1.86)	1083:1130	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	3	100	theme	TDZ	992:994	arg1	combinations					917:928	combinations	917:928	combinations	917:928	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	3	100	theme	TDZ	992:994	arg1	concentrations					898:911	28 different concentrations	885:911	28 different concentrations	885:911	Various types of explants (leaf, petiole, root, hypocotyl, and node) were cultured on MS medium containing 28 different concentrations and combinations of PGRs [thidiazuron (TDZ) and naphthalene acetic acid (NAA), TDZ and indole-3-acetic acid (IAA), benzyl adenine (BA) and NAA, alone TDZ, and alone BA].
31790925	9	101	theme	secondary	1905:1913	arg1	metabolites					1915:1925	secondary metabolites	1905:1925	secondary metabolites	1905:1925	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	0	102	theme	nodal	55:59	arg1	explants					75:82	nodal and hypocotyl explants	55:82	explants	75:82	Efficient plant regeneration and callus induction from nodal and hypocotyl explants of goji berry (Lycium barbarum L.) and comparison of phenolic profiles in calli formed under different combinations of plant growth regulators.
31790925	4	103	theme	highest	1087:1093	arg1	number					1100:1105	The highest mean number	1083:1105	The highest mean number of shoots (23.33 ± 1.86)	1083:1130	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	4	104	contain	containing	1217:1226	arg1	medium					1210:1215	medium	1210:1215	medium containing 0.5 mg/l BA alone	1210:1244	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	4	104	contain	containing	1217:1226	arg2	BA					1237:1238	0.5 mg/l BA	1228:1238	0.5 mg/l BA alone	1228:1244	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	1	105	theme	many	280:283	arg1	effects					296:302	many beneficial effects	280:302	many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health	280:404	Goji berry (Lycium barbarum L.) is a fruit that has many beneficial effects (such as antidiabetic, antioxidant, anticancer, antidepressant, and immunomodulatory) on human health because of several dietary constituents such as phenolics, vitamins, carotenoids, and polysaccharides.
31790925	10	106	theme	secondary	2129:2137	arg1	metabolites					2139:2149	goji secondary metabolites	2124:2149	goji secondary metabolites	2124:2149	The culture protocol described in this paper could be employed for the development of novel methods for the commercial production of goji secondary metabolites.
31790925	8	107	theme	TDZ/IAA	1659:1665	arg1	combination					1667:1677	The TDZ/IAA combination	1655:1677	The TDZ/IAA combination	1655:1677	The TDZ/IAA combination, TDZ alone, and TDZ/NAA combination significantly increased vanillic acid and rutin, gallic acid, and quercetin synthesis, respectively.
31790925	5	108	theme	0.25 mg/l	1338:1346	arg1	TDZ					1348:1350	0.25 mg/l TDZ	1338:1350	0.25 mg/l TDZ	1338:1350	The highest mean callus diameter was obtained from hypocotyl explants on medium containing 0.25 mg/l TDZ and 0.1 mg/l IAA (21.40 ± 0.71 mm).
31790925	9	109	theme	accumulation	1949:1960	arg1	kinds					1896:1900	different kinds	1886:1900	different kinds of secondary metabolites and affect/accelerate accumulation	1886:1960	These outcomes indicate that different PGRs lead to the production of different kinds of secondary metabolites and affect/accelerate accumulation in the callus of goji berry.
31790925	2	110	theme	regulators	746:755	arg1	combinations					717:728	various combinations	709:728	various combinations of plant growth regulators (PGRs)	709:762	In order to develop in vitro culture protocols for callus induction and plant regeneration from different explants of Goji plants and to compare the phenolic composition in calli of different origin, various combinations of plant growth regulators (PGRs) were applied.
31790925	4	111	theme	formation	1156:1164	arg1	percentage					1136:1145	percentage	1136:1145	percentage of shoot formation (100%)	1136:1171	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	4	111	theme	formation	1156:1164	arg1	%					1170:1170	100%	1167:1170	100%	1167:1170	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31790925	4	111	theme	formation	1156:1164	arg1	number					1100:1105	The highest mean number	1083:1105	The highest mean number of shoots (23.33 ± 1.86)	1083:1130	The highest mean number of shoots (23.33 ± 1.86) and percentage of shoot formation (100%) were obtained from nodal explants on medium containing 0.5 mg/l BA alone.
31133998	2	0	with	interactions	344:355	arg1	mechanisms					409:418	the mechanisms	405:418	the mechanisms of sulfur oxidation by acidophiles	405:453	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	2	0	with	interactions	344:355	arg1	sulfur					387:392	elemental sulfur	377:392	elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles,	377:484	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	2	0	with	interactions	344:355	arg1	thermoacidophiles					467:483	thermoacidophiles	467:483	especially thermoacidophiles	456:483	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	6	1	theme	various	1217:1223	arg1	glycoconjugates					1225:1239	various glycoconjugates	1217:1239	various glycoconjugates	1217:1239	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	1	2	theme	environmental	254:266	arg1	issues					268:273	environmental issues	254:273	environmental issues	254:273	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	0	3	dep	Dynamics	86:93	arg1	Insight					0:6	Insight	0:6	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur	0:75	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis.
31133998	5	4	theme	laser	637:641	arg1	CLSM					664:667	CLSM	664:667	CLSM	664:667	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	4	theme	laser	637:641	arg1	microscopy					652:661	Confocal laser scanning microscopy	628:661	Confocal laser scanning microscopy (CLSM)	628:668	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	9	5	theme	sugar	1635:1639	arg1	types					1641:1645	sugar types	1635:1645	EPS composition as well as sugar types in EPS	1608:1652	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	6	6	theme	EPS	1192:1194	arg1	matrix					1196:1201	an EPS matrix	1189:1201	an EPS matrix consisting of various glycoconjugates	1189:1239	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	5	7	theme	single	818:823	arg1	colonies					825:832	single colonies	818:832	single colonies	818:832	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	6	8	theme	intial	1100:1105	arg1	attachment					1107:1116	intial attachment	1100:1116	intial attachment	1100:1116	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	3	9	dep	sp	569:570	arg1	Acidianus					559:567	a crenarchaeal isolate Acidianus	536:567	a crenarchaeal isolate Acidianus	536:567	This work focused on how a crenarchaeal isolate Acidianus sp.
31133998	7	10	theme	main	1332:1335	arg1	lipids					1300:1305	lipids	1300:1305	lipids	1300:1305	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	10	theme	main	1332:1335	arg1	acids					1318:1322	uronic acids	1311:1322	uronic acids	1311:1322	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	10	theme	main	1332:1335	arg1	proteins					1290:1297	proteins	1290:1297	proteins	1290:1297	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	10	theme	main	1332:1335	arg1	carbohydrates					1275:1287	carbohydrates	1275:1287	carbohydrates	1275:1287	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	10	theme	main	1332:1335	arg1	components					1337:1346	the main components	1328:1346	the main components	1328:1346	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	4	11	theme	elemental	598:606	arg1	sulfur					608:613	elemental sulfur	598:613	elemental sulfur	598:613	DSM 29099 interacts with elemental sulfur.
31133998	5	12	with	structures	882:891	arg1	diameter					900:907	a diameter	898:907	a diameter of up to 100 μm	898:923	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	8	13	from	monosaccharides	1568:1582	arg1	polysaccharides					1591:1605	EPS polysaccharides	1587:1605	EPS polysaccharides	1587:1605	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	1	14	theme	particular	199:208	arg1	interest					210:217	particular interest	199:217	particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD)	199:318	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	9	15	from	types	1641:1645	arg1	EPS					1650:1652	EPS	1650:1652	EPS	1650:1652	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	8	16	theme	-Fourier	1377:1384	arg1	FTIR					1424:1427	FTIR	1424:1427	FTIR	1424:1427	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	16	theme	-Fourier	1377:1384	arg1	spectroscopy					1410:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy	1349:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR)	1349:1428	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	5	17	dep	100	918:920	arg1	to					915:916	to	915:916	to	915:916	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	18	theme	force	681:685	arg1	AFM					699:701	AFM	699:701	AFM	699:701	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	18	theme	force	681:685	arg1	microscopy					687:696	Atomic force microscopy	674:696	Atomic force microscopy (AFM)	674:702	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	8	19	theme	infrared	1401:1408	arg1	FTIR					1424:1427	FTIR	1424:1427	FTIR	1424:1427	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	19	theme	infrared	1401:1408	arg1	spectroscopy					1410:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy	1349:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR)	1349:1428	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	7	20	theme	uronic	1311:1316	arg1	lipids					1300:1305	lipids	1300:1305	lipids	1300:1305	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	20	theme	uronic	1311:1316	arg1	acids					1318:1322	uronic acids	1311:1322	uronic acids	1311:1322	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	20	theme	uronic	1311:1316	arg1	proteins					1290:1297	proteins	1290:1297	proteins	1290:1297	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	20	theme	uronic	1311:1316	arg1	carbohydrates					1275:1287	carbohydrates	1275:1287	carbohydrates	1275:1287	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	7	20	theme	uronic	1311:1316	arg1	components					1337:1346	the main components	1328:1346	the main components	1328:1346	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	3	21	theme	isolate	551:557	arg1	Acidianus					559:567	a crenarchaeal isolate Acidianus	536:567	a crenarchaeal isolate Acidianus	536:567	This work focused on how a crenarchaeal isolate Acidianus sp.
31133998	6	22	theme	biofilm	1153:1159	arg1	cells					1161:1165	biofilm cells	1153:1165	biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates	1153:1239	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	23	from	cells	1161:1165	arg1	rich					1145:1148	rich	1145:1148	rich	1145:1148	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	5	24	from	colonies	825:832	arg1	structures					882:891	3-D structures	878:891	3-D structures with a diameter of up to 100 μm	878:923	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	24	from	colonies	825:832	arg1	stage					859:863	first stage	853:863	first stage	853:863	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	1	25	theme	inorganic	137:145	arg1	compounds					154:162	reduced inorganic sulfur compounds	129:162	reduced inorganic sulfur compounds (RISCs)	129:170	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	1	25	theme	inorganic	137:145	arg1	RISCs					165:169	RISCs	165:169	RISCs	165:169	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	6	26	theme	extracellular	942:954	arg1	EPS					978:980	EPS	978:980	EPS	978:980	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	26	theme	extracellular	942:954	arg1	substances					966:975	extracellular polymeric substances	942:975	extracellular polymeric substances (EPS)	942:981	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	27	theme	rich	1145:1148	arg1	footprints					1134:1143	footprints	1134:1143	footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates	1134:1239	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	9	28	dep	substrate	1672:1680	arg1	sulfur					1683:1688	sulfur	1683:1688	sulfur	1683:1688	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	9	28	dep	substrate	1672:1680	arg1	tetrathionate					1693:1705	tetrathionate	1693:1705	tetrathionate	1693:1705	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	1	29	theme	compounds	154:162	arg1	Biooxidation					113:124	Biooxidation	113:124	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles	113:191	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	8	30	theme	high-performance	1434:1449	arg1	chromatography					1466:1479	high-performance anion exchange chromatography	1434:1479	high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD)	1434:1525	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	0	31	theme	Biofilm	78:84	arg1	Dynamics					86:93	Biofilm Dynamics	78:93	Biofilm Dynamics	78:93	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis.
31133998	5	32	theme	first	853:857	arg1	stage					859:863	first stage	853:863	first stage	853:863	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	8	33	theme	exchange	1457:1464	arg1	chromatography					1466:1479	high-performance anion exchange chromatography	1434:1479	high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD)	1434:1525	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	5	34	from	biofilms	768:775	arg1	sulfur					790:795	elemental sulfur	780:795	elemental sulfur	780:795	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	9	35	theme	planktonic	1736:1745	arg1	cells					1747:1751	planktonic cells	1736:1751	planktonic cells	1736:1751	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	8	36	with	chromatography	1466:1479	arg1	HPAE-PAD					1517:1524	HPAE-PAD	1517:1524	HPAE-PAD	1517:1524	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	36	with	chromatography	1466:1479	arg1	detection					1506:1514	pulsed amperometric detection	1486:1514	pulsed amperometric detection (HPAE-PAD)	1486:1525	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	6	37	theme	non-destructive	988:1002	arg1	approach					1011:1018	a non-destructive lectin approach	986:1018	a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes	986:1087	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	37	theme	non-destructive	988:1002	arg1	analysis					1051:1058	fluorescence lectin-barcoding analysis	1021:1058	fluorescence lectin-barcoding analysis	1021:1058	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	8	38	theme	amperometric	1493:1504	arg1	HPAE-PAD					1517:1524	HPAE-PAD	1517:1524	HPAE-PAD	1517:1524	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	38	theme	amperometric	1493:1504	arg1	detection					1506:1514	pulsed amperometric detection	1486:1514	pulsed amperometric detection (HPAE-PAD)	1486:1525	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	10	39	from	information	1775:1785	arg1	up					1815:1816	the building blocks/make up	1790:1816	the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments	1790:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	10	39	from	information	1775:1785	arg1	dynamics					1829:1836	dynamics	1829:1836	the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments	1790:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	0	40	theme	Thermoacidophilic	29:45	arg1	Archaea					47:53	Thermoacidophilic Archaea	29:53	Thermoacidophilic Archaea	29:53	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis.
31133998	1	41	theme	acid	295:298	arg1	AMD					315:317	AMD	315:317	AMD	315:317	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	1	41	theme	acid	295:298	arg1	drainage					305:312	acid mine drainage	295:312	acid mine drainage (AMD)	295:318	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	6	42	theme	substances	966:975	arg1	analysis					930:937	The analysis	926:937	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes	926:1087	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	2	43	theme	oxidation	430:438	arg1	mechanisms					409:418	the mechanisms	405:418	the mechanisms of sulfur oxidation by acidophiles	405:453	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	2	43	theme	oxidation	430:438	arg1	sulfur					387:392	elemental sulfur	377:392	elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles,	377:484	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	2	43	theme	oxidation	430:438	arg1	thermoacidophiles					467:483	thermoacidophiles	467:483	especially thermoacidophiles	456:483	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	10	44	theme	building	1794:1801	arg1	up					1815:1816	the building blocks/make up	1790:1816	the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments	1790:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	8	45	theme	Attenuated	1349:1358	arg1	FTIR					1424:1427	FTIR	1424:1427	FTIR	1424:1427	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	45	theme	Attenuated	1349:1358	arg1	spectroscopy					1410:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy	1349:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR)	1349:1428	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	0	46	with	Interactions	13:24	arg1	Sulfur					70:75	Elemental Sulfur	60:75	Elemental Sulfur	60:75	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis.
31133998	8	47	with	spectroscopy	1410:1421	arg1	HPAE-PAD					1517:1524	HPAE-PAD	1517:1524	HPAE-PAD	1517:1524	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	47	with	spectroscopy	1410:1421	arg1	detection					1506:1514	pulsed amperometric detection	1486:1514	pulsed amperometric detection (HPAE-PAD)	1486:1525	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	5	48	from	Analysis	616:623	arg1	combination					707:717	combination	707:717	combination with Epifluorescence microscopy (EFM)	707:755	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	1	49	dep	formation	282:290	arg1	e.g.					276:279	e.g.	276:279	e.g.	276:279	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	5	50	theme	μm	922:923	arg1	diameter					900:907	a diameter	898:907	a diameter of up to 100 μm	898:923	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	7	51	theme	Wet	1242:1244	arg1	data					1256:1259	Wet chemistry data	1242:1259	Wet chemistry data	1242:1259	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	2	52	theme	interfacial	332:342	arg1	interactions					344:355	interfacial interactions	332:355	interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles,	332:484	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	9	53	theme	EPS	1608:1610	arg1	composition					1612:1622	EPS composition	1608:1622	EPS composition as well as sugar types in EPS	1608:1652	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	6	54	theme	fluorescence	1021:1032	arg1	approach					1011:1018	a non-destructive lectin approach	986:1018	a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes	986:1087	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	54	theme	fluorescence	1021:1032	arg1	analysis					1051:1058	fluorescence lectin-barcoding analysis	1021:1058	fluorescence lectin-barcoding analysis	1021:1058	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	10	55	theme	thermoacidophilic	1853:1869	arg1	archaea					1871:1877	thermoacidophilic archaea	1853:1877	thermoacidophilic archaea	1853:1877	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	10	56	from	up	1815:1816	arg1	environments					1899:1910	extremely acidic environments	1882:1910	extremely acidic environments	1882:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	8	57	theme	EPS	1587:1589	arg1	polysaccharides					1591:1605	EPS polysaccharides	1587:1605	EPS polysaccharides	1587:1605	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	10	58	theme	biofilms	1841:1848	arg1	up					1815:1816	the building blocks/make up	1790:1816	the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments	1790:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	10	58	theme	biofilms	1841:1848	arg1	dynamics					1829:1836	dynamics	1829:1836	the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments	1790:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	5	59	theme	Confocal	628:635	arg1	CLSM					664:667	CLSM	664:667	CLSM	664:667	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	59	theme	Confocal	628:635	arg1	microscopy					652:661	Confocal laser scanning microscopy	628:661	Confocal laser scanning microscopy (CLSM)	628:668	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	6	60	from	matrix	1196:1201	arg1	embedded					1177:1184	embedded	1177:1184	embedded	1177:1184	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	10	61	theme	acidic	1892:1897	arg1	environments					1899:1910	extremely acidic environments	1882:1910	extremely acidic environments	1882:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	10	62	from	dynamics	1829:1836	arg1	environments					1899:1910	extremely acidic environments	1882:1910	extremely acidic environments	1882:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	1	63	theme	drainage	305:312	arg1	formation					282:290	formation	282:290	formation of acid mine drainage (AMD)	282:318	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	5	64	theme	Epifluorescence	724:738	arg1	EFM					752:754	EFM	752:754	EFM	752:754	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	64	theme	Epifluorescence	724:738	arg1	microscopy					740:749	Epifluorescence microscopy	724:749	Epifluorescence microscopy (EFM)	724:755	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	9	65	dep	lifestyle	1712:1720	arg1	biofilms					1723:1730	biofilms	1723:1730	biofilms	1723:1730	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	9	65	dep	lifestyle	1712:1720	arg1	cells					1747:1751	planktonic cells	1736:1751	planktonic cells	1736:1751	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	5	66	theme	elemental	780:788	arg1	sulfur					790:795	elemental sulfur	780:795	elemental sulfur	780:795	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	8	67	theme	transformation	1386:1399	arg1	FTIR					1424:1427	FTIR	1424:1427	FTIR	1424:1427	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	67	theme	transformation	1386:1399	arg1	spectroscopy					1410:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy	1349:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR)	1349:1428	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	5	68	theme	Atomic	674:679	arg1	AFM					699:701	AFM	699:701	AFM	699:701	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	68	theme	Atomic	674:679	arg1	microscopy					687:696	Atomic force microscopy	674:696	Atomic force microscopy (AFM)	674:702	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	69	theme	scanning	643:650	arg1	CLSM					664:667	CLSM	664:667	CLSM	664:667	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	69	theme	scanning	643:650	arg1	microscopy					652:661	Confocal laser scanning microscopy	628:661	Confocal laser scanning microscopy (CLSM)	628:668	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	3	70	theme	crenarchaeal	538:549	arg1	Acidianus					559:567	a crenarchaeal isolate Acidianus	536:567	a crenarchaeal isolate Acidianus	536:567	This work focused on how a crenarchaeal isolate Acidianus sp.
31133998	9	71	from	composition	1612:1622	arg1	EPS					1650:1652	EPS	1650:1652	EPS	1650:1652	EPS composition as well as sugar types in EPS vary according to substrate (sulfur or tetrathionate) and lifestyle (biofilms and planktonic cells).
31133998	1	72	theme	reduced	129:135	arg1	compounds					154:162	reduced inorganic sulfur compounds	129:162	reduced inorganic sulfur compounds (RISCs)	129:170	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	1	72	theme	reduced	129:135	arg1	RISCs					165:169	RISCs	165:169	RISCs	165:169	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	6	73	theme	polymeric	956:964	arg1	EPS					978:980	EPS	978:980	EPS	978:980	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	73	theme	polymeric	956:964	arg1	substances					966:975	extracellular polymeric substances	942:975	extracellular polymeric substances (EPS)	942:981	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	74	from	embedded	1177:1184	arg1	matrix					1196:1201	an EPS matrix	1189:1201	an EPS matrix consisting of various glycoconjugates	1189:1239	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	1	75	theme	sulfur	147:152	arg1	compounds					154:162	reduced inorganic sulfur compounds	129:162	reduced inorganic sulfur compounds (RISCs)	129:170	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	1	75	theme	sulfur	147:152	arg1	RISCs					165:169	RISCs	165:169	RISCs	165:169	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	8	76	theme	anion	1451:1455	arg1	chromatography					1466:1479	high-performance anion exchange chromatography	1434:1479	high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD)	1434:1525	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	5	77	with	combination	707:717	arg1	EFM					752:754	EFM	752:754	EFM	752:754	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	77	with	combination	707:717	arg1	microscopy					740:749	Epifluorescence microscopy	724:749	Epifluorescence microscopy (EFM)	724:755	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	4	78	theme	DSM	573:575	arg1	29099					577:581	DSM 29099	573:581	DSM 29099	573:581	DSM 29099 interacts with elemental sulfur.
31133998	6	79	from	rich	1145:1148	arg1	cells					1161:1165	biofilm cells	1153:1165	biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates	1153:1239	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	0	80	theme	EPS	99:101	arg1	Analysis					103:110	EPS Analysis	99:110	EPS Analysis	99:110	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis.
31133998	8	81	theme	pulsed	1486:1491	arg1	HPAE-PAD					1517:1524	HPAE-PAD	1517:1524	HPAE-PAD	1517:1524	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	81	theme	pulsed	1486:1491	arg1	detection					1506:1514	pulsed amperometric detection	1486:1514	pulsed amperometric detection (HPAE-PAD)	1486:1525	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	5	82	from	monolayer	840:848	arg1	structures					882:891	3-D structures	878:891	3-D structures with a diameter of up to 100 μm	878:923	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	5	82	from	monolayer	840:848	arg1	stage					859:863	first stage	853:863	first stage	853:863	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	6	83	theme	lectin	1004:1009	arg1	approach					1011:1018	a non-destructive lectin approach	986:1018	a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes	986:1087	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	83	theme	lectin	1004:1009	arg1	analysis					1051:1058	fluorescence lectin-barcoding analysis	1021:1058	fluorescence lectin-barcoding analysis	1021:1058	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	2	84	theme	acidophiles	360:370	arg1	interactions					344:355	interfacial interactions	332:355	interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles,	332:484	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	5	85	theme	3-D	878:880	arg1	structures					882:891	3-D structures	878:891	3-D structures with a diameter of up to 100 μm	878:923	Analysis by Confocal laser scanning microscopy (CLSM) and Atomic force microscopy (AFM) in combination with Epifluorescence microscopy (EFM) shows that biofilms on elemental sulfur are characterized by single colonies and a monolayer in first stage and later on 3-D structures with a diameter of up to 100 μm.
31133998	7	86	theme	chemistry	1246:1254	arg1	data					1256:1259	Wet chemistry data	1242:1259	Wet chemistry data	1242:1259	Wet chemistry data indicate that carbohydrates, proteins, lipids and uronic acids are the main components.
31133998	0	87	theme	Archaea	47:53	arg1	Interactions					13:24	Interactions	13:24	Interactions of Thermoacidophilic Archaea With Elemental Sulfur	13:75	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis.
31133998	10	88	theme	blocks/make	1803:1813	arg1	up					1815:1816	the building blocks/make up	1790:1816	the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments	1790:1910	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
31133998	2	89	theme	elemental	377:385	arg1	sulfur					387:392	elemental sulfur	377:392	elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles,	377:484	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	0	90	theme	Elemental	60:68	arg1	Sulfur					70:75	Elemental Sulfur	60:75	Elemental Sulfur	60:75	Insight Into Interactions of Thermoacidophilic Archaea With Elemental Sulfur: Biofilm Dynamics and EPS Analysis.
31133998	1	91	theme	mine	300:303	arg1	AMD					315:317	AMD	315:317	AMD	315:317	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	1	91	theme	mine	300:303	arg1	drainage					305:312	acid mine drainage	295:312	acid mine drainage (AMD)	295:318	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	6	92	theme	several	1067:1073	arg1	fluorochromes					1075:1087	several fluorochromes	1067:1087	several fluorochromes	1067:1087	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	2	93	theme	sulfur	423:428	arg1	oxidation					430:438	sulfur oxidation	423:438	sulfur oxidation by acidophiles	423:453	Up to now, interfacial interactions of acidophiles with elemental sulfur as well as the mechanisms of sulfur oxidation by acidophiles, especially thermoacidophiles, are not yet fully clear.
31133998	8	94	theme	main	1563:1566	arg1	monosaccharides					1568:1582	the main monosaccharides	1559:1582	the main monosaccharides in EPS polysaccharides	1559:1605	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	95	theme	reflectance	1360:1370	arg1	FTIR					1424:1427	FTIR	1424:1427	FTIR	1424:1427	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	8	95	theme	reflectance	1360:1370	arg1	spectroscopy					1410:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy	1349:1421	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR)	1349:1428	Attenuated reflectance (ATR)-Fourier transformation infrared spectroscopy (FTIR) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAE-PAD) indicate glucose and mannose as the main monosaccharides in EPS polysaccharides.
31133998	1	96	theme	biomining	227:235	arg1	industry					237:244	the biomining industry	223:244	the biomining industry	223:244	Biooxidation of reduced inorganic sulfur compounds (RISCs) by thermoacidophiles is of particular interest for the biomining industry and for environmental issues, e.g., formation of acid mine drainage (AMD).
31133998	6	97	theme	lectin-barcoding	1034:1049	arg1	approach					1011:1018	a non-destructive lectin approach	986:1018	a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes	986:1087	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	6	97	theme	lectin-barcoding	1034:1049	arg1	analysis					1051:1058	fluorescence lectin-barcoding analysis	1021:1058	fluorescence lectin-barcoding analysis	1021:1058	The analysis of extracellular polymeric substances (EPS) by a non-destructive lectin approach (fluorescence lectin-barcoding analysis) using several fluorochromes shows that intial attachment was featured by footprints rich in biofilm cells that were embedded in an EPS matrix consisting of various glycoconjugates.
31133998	10	98	theme	archaea	1871:1877	arg1	biofilms					1841:1848	biofilms	1841:1848	biofilms of thermoacidophilic archaea	1841:1877	This study provides information on the building blocks/make up as well as dynamics of biofilms of thermoacidophilic archaea in extremely acidic environments.
29805493	3	0	theme	present	336:342	arg1	study					344:348	the present study	332:348	the present study	332:348	were investigated in the present study.
29805493	7	1	theme	ICR	715:717	arg1	mice					719:722	ICR mice	715:722	ICR mice	715:722	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	10	2	theme	mouse	1182:1186	arg1	count					1198:1202	The mouse leukocyte count	1178:1202	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes	1178:1263	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	12	3	theme	necrosis	1448:1455	arg1	levels					1432:1437	The levels	1428:1437	The levels of tumor necrosis factor-α and interferon-γ	1428:1481	The levels of tumor necrosis factor-α and interferon-γ were measured by ELISA.
29805493	0	4	from	effect	17:22	arg1	mice					100:103	cyclophosphamide-induced immunocompromised mice	57:103	cyclophosphamide-induced immunocompromised mice	57:103	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.
29805493	8	5	theme	model	985:989	arg1	groups					991:996	the control and model groups	969:996	groups	991:996	The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water.
29805493	4	6	theme	water	409:413	arg1	extraction					415:424	water extraction	409:424	water extraction	409:424	The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods.
29805493	1	7	theme	chinensis	285:293	arg1	fruit					265:269	the fruit	261:269	the fruit of Schisandra chinensis	261:293	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	15	8	theme	Cyp-induced	1772:1782	arg1	impairment					1784:1793	Cyp-induced impairment	1772:1793	Cyp-induced impairment of the cellular, humoral and non-specific immunity	1772:1844	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	14	9	theme	flow	1706:1709	arg1	analysis					1722:1729	flow cytometric analysis	1706:1729	flow cytometric analysis	1706:1729	The apoptotic rate of splenic lymphocytes was determined by flow cytometric analysis.
29805493	10	10	theme	carbon	1347:1352	arg1	test					1364:1367	a carbon clearance test	1345:1367	a carbon clearance test	1345:1367	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	13	11	theme	antibody	1520:1527	arg1	formation					1529:1537	antibody formation	1520:1537	antibody formation	1520:1537	Furthermore, antibody formation and spleen lymphocyte proliferation were measured by the serum hemolysin and the MTT method, respectively.
29805493	9	12	theme	model	1082:1086	arg1	groups					1096:1101	the model and SCP groups	1078:1101	groups	1096:1101	Subsequently, the mice in the model and SCP groups were intraperitoneally injected with Cyp (20 mg/kg) once a day for 5 days.
29805493	10	13	theme	phagocytic	1290:1299	arg1	function					1301:1308	the phagocytic function	1286:1308	the phagocytic function of macrophages	1286:1323	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	10	14	theme	peripheral	1211:1220	arg1	blood					1222:1226	the peripheral blood	1207:1226	the peripheral blood as well as thymus and spleen indexes	1207:1263	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	7	15	theme	low-dose	767:774	arg1	SCP					776:778	low-dose SCP	767:778	low-dose SCP (0.4 mg/10 g)	767:792	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	15	theme	low-dose	767:774	arg1	control					751:757	control	751:757	control	751:757	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	15	theme	low-dose	767:774	arg1	g					791:791	0.4 mg/10 g	781:791	0.4 mg/10 g	781:791	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	8	16	theme	same	1020:1023	arg1	volume					1025:1030	the same volume	1016:1030	the same volume of distilled water	1016:1049	The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water.
29805493	15	17	theme	immune	1909:1914	arg1	hypofunction					1916:1927	immune hypofunction	1909:1927	immune hypofunction	1909:1927	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	14	18	theme	apoptotic	1650:1658	arg1	rate					1660:1663	The apoptotic rate	1646:1663	The apoptotic rate of splenic lymphocytes	1646:1686	The apoptotic rate of splenic lymphocytes was determined by flow cytometric analysis.
29805493	15	19	theme	immunity	1837:1844	arg1	impairment					1784:1793	Cyp-induced impairment	1772:1793	Cyp-induced impairment of the cellular, humoral and non-specific immunity	1772:1844	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	14	20	theme	splenic	1668:1674	arg1	lymphocytes					1676:1686	splenic lymphocytes	1668:1686	splenic lymphocytes	1668:1686	The apoptotic rate of splenic lymphocytes was determined by flow cytometric analysis.
29805493	13	21	theme	spleen	1543:1548	arg1	proliferation					1561:1573	spleen lymphocyte proliferation	1543:1573	spleen lymphocyte proliferation	1543:1573	Furthermore, antibody formation and spleen lymphocyte proliferation were measured by the serum hemolysin and the MTT method, respectively.
29805493	6	22	theme	SCP	653:655	arg1	composition					638:648	The monosaccharide composition	619:648	The monosaccharide composition of SCP	619:655	The monosaccharide composition of SCP was determined by high-performance liquid chromatography.
29805493	13	23	theme	MTT	1620:1622	arg1	method					1624:1629	the MTT method	1616:1629	the MTT method	1616:1629	Furthermore, antibody formation and spleen lymphocyte proliferation were measured by the serum hemolysin and the MTT method, respectively.
29805493	15	24	theme	cellular	1802:1809	arg1	immunity					1837:1844	the cellular, humoral and non-specific immunity	1798:1844	immunity	1837:1844	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	8	25	theme	SCP	881:883	arg1	groups					885:890	the SCP groups	877:890	the SCP groups	877:890	The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water.
29805493	7	26	theme	mg/10	848:852	arg1	SCP					839:841	high-dose SCP	829:841	high-dose SCP (1.6 mg/10 g)	829:855	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	26	theme	mg/10	848:852	arg1	g					854:854	1.6 mg/10 g	844:854	1.6 mg/10 g	844:854	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	1	27	theme	immunomodulatory	203:218	arg1	effects					220:226	the immunomodulatory effects	199:226	the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis	199:293	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	0	28	theme	Immunomodulatory	0:15	arg1	effect					17:22	Immunomodulatory effect	0:22	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.	0:104	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.
29805493	15	29	theme	auxiliary	1861:1869	arg1	enhancer					1878:1885	an auxiliary immune enhancer	1858:1885	an auxiliary immune enhancer for the prevention of immune hypofunction	1858:1927	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	10	30	theme	leukocyte	1188:1196	arg1	count					1198:1202	The mouse leukocyte count	1178:1202	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes	1178:1263	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	5	31	theme	uronic	485:490	arg1	acid					492:495	uronic acid	485:495	uronic acid	485:495	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	10	32	theme	clearance	1354:1362	arg1	test					1364:1367	a carbon clearance test	1345:1367	a carbon clearance test	1345:1367	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	0	33	theme	Schisandra	27:36	arg1	polysaccharides					38:52	Schisandra polysaccharides	27:52	Schisandra polysaccharides	27:52	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.
29805493	8	34	theme	water	1045:1049	arg1	volume					1025:1030	the same volume	1016:1030	the same volume of distilled water	1016:1049	The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water.
29805493	8	35	theme	control	973:979	arg1	groups					991:996	the control and model groups	969:996	groups	991:996	The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water.
29805493	5	36	theme	acid	492:495	arg1	contents					509:516	The total carbohydrate, uronic acid and protein contents	461:516	The total carbohydrate, uronic acid and protein contents	461:516	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	10	37	from	count	1198:1202	arg1	thymus					1239:1244	thymus	1239:1244	thymus	1239:1244	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	10	37	from	count	1198:1202	arg1	blood					1222:1226	the peripheral blood	1207:1226	the peripheral blood as well as thymus and spleen indexes	1207:1263	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	6	38	theme	monosaccharide	623:636	arg1	composition					638:648	The monosaccharide composition	619:648	The monosaccharide composition of SCP	619:655	The monosaccharide composition of SCP was determined by high-performance liquid chromatography.
29805493	8	39	theme	distilled	1035:1043	arg1	water					1045:1049	distilled water	1035:1049	distilled water	1035:1049	The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water.
29805493	7	40	theme	high-dose	829:837	arg1	SCP					839:841	high-dose SCP	829:841	high-dose SCP (1.6 mg/10 g)	829:855	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	40	theme	high-dose	829:837	arg1	control					751:757	control	751:757	control	751:757	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	40	theme	high-dose	829:837	arg1	g					854:854	1.6 mg/10 g	844:854	1.6 mg/10 g	844:854	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	15	41	theme	non-specific	1824:1835	arg1	immunity					1837:1844	the cellular, humoral and non-specific immunity	1798:1844	immunity	1837:1844	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	7	42	theme	mg/10	816:820	arg1	SCP					807:809	medium-dose SCP	795:809	medium-dose SCP (0.8 mg/10 g)	795:823	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	42	theme	mg/10	816:820	arg1	g					822:822	0.8 mg/10 g	812:822	0.8 mg/10 g	812:822	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	13	43	theme	serum	1596:1600	arg1	hemolysin					1602:1610	the serum hemolysin	1592:1610	the serum hemolysin	1592:1610	Furthermore, antibody formation and spleen lymphocyte proliferation were measured by the serum hemolysin and the MTT method, respectively.
29805493	8	44	from	mice	869:872	arg1	groups					885:890	the SCP groups	877:890	the SCP groups	877:890	The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water.
29805493	5	45	theme	protein	501:507	arg1	contents					509:516	The total carbohydrate, uronic acid and protein contents	461:516	The total carbohydrate, uronic acid and protein contents	461:516	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	1	46	theme	polysaccharide	235:248	arg1	extract					250:256	the polysaccharide extract	231:256	the polysaccharide extract of the fruit of Schisandra chinensis	231:293	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	0	47	theme	polysaccharides	38:52	arg1	effect					17:22	Immunomodulatory effect	0:22	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.	0:104	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.
29805493	12	48	theme	tumor	1442:1446	arg1	necrosis					1448:1455	tumor necrosis factor-α and interferon-γ	1442:1481	tumor necrosis factor-α and interferon-γ	1442:1481	The levels of tumor necrosis factor-α and interferon-γ were measured by ELISA.
29805493	12	49	dep	necrosis	1448:1455	arg1	factor-α					1457:1464	factor-α	1457:1464	factor-α	1457:1464	The levels of tumor necrosis factor-α and interferon-γ were measured by ELISA.
29805493	12	49	dep	necrosis	1448:1455	arg1	interferon-γ					1470:1481	interferon-γ	1470:1481	interferon-γ	1470:1481	The levels of tumor necrosis factor-α and interferon-γ were measured by ELISA.
29805493	1	50	dep	effects	220:226	arg1	strategy					111:118	a strategy	109:118	a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp)	109:196	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	1	50	dep	effects	220:226	arg1	Turcz					296:300	Turcz	296:300	Turcz	296:300	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	5	51	theme	m-hydroxydiphenyl	566:582	arg1	method					597:602	the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method	540:602	method	597:602	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	1	52	theme	extract	250:256	arg1	effects					220:226	the immunomodulatory effects	199:226	the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis	199:293	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	0	53	theme	immunocompromised	82:98	arg1	mice					100:103	cyclophosphamide-induced immunocompromised mice	57:103	cyclophosphamide-induced immunocompromised mice	57:103	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.
29805493	13	54	theme	lymphocyte	1550:1559	arg1	proliferation					1561:1573	spleen lymphocyte proliferation	1543:1573	spleen lymphocyte proliferation	1543:1573	Furthermore, antibody formation and spleen lymphocyte proliferation were measured by the serum hemolysin and the MTT method, respectively.
29805493	7	55	theme	control	751:757	arg1	groups					857:862	control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups	751:862	control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups	751:862	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	15	56	theme	humoral	1812:1818	arg1	immunity					1837:1844	the cellular, humoral and non-specific immunity	1798:1844	immunity	1837:1844	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	4	57	theme	crude	355:359	arg1	SCP					388:390	SCP	388:390	SCP	388:390	The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods.
29805493	4	57	theme	crude	355:359	arg1	polysaccharide					372:385	The crude Schisandra polysaccharide	351:385	The crude Schisandra polysaccharide (SCP)	351:391	The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods.
29805493	1	58	theme	well-known	135:144	arg1	effects					164:170	the well-known immunosuppressant effects	131:170	the well-known immunosuppressant effects of cyclophosphamide (Cyp)	131:196	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	0	59	theme	cyclophosphamide-induced	57:80	arg1	mice					100:103	cyclophosphamide-induced immunocompromised mice	57:103	cyclophosphamide-induced immunocompromised mice	57:103	Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide-induced immunocompromised mice.
29805493	14	60	theme	cytometric	1711:1720	arg1	analysis					1722:1729	flow cytometric analysis	1706:1729	flow cytometric analysis	1706:1729	The apoptotic rate of splenic lymphocytes was determined by flow cytometric analysis.
29805493	4	61	theme	precipitation	438:450	arg1	methods					452:458	alcohol precipitation methods	430:458	alcohol precipitation methods	430:458	The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods.
29805493	5	62	theme	Bradford	588:595	arg1	method					597:602	the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method	540:602	method	597:602	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	1	63	theme	immunosuppressant	146:162	arg1	effects					164:170	the well-known immunosuppressant effects	131:170	the well-known immunosuppressant effects of cyclophosphamide (Cyp)	131:196	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	7	64	theme	medium-dose	795:805	arg1	SCP					807:809	medium-dose SCP	795:809	medium-dose SCP (0.8 mg/10 g)	795:823	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	64	theme	medium-dose	795:805	arg1	control					751:757	control	751:757	control	751:757	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	64	theme	medium-dose	795:805	arg1	g					822:822	0.8 mg/10 g	812:822	0.8 mg/10 g	812:822	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	15	65	theme	immune	1871:1876	arg1	enhancer					1878:1885	an auxiliary immune enhancer	1858:1885	an auxiliary immune enhancer for the prevention of immune hypofunction	1858:1927	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	4	66	theme	alcohol	430:436	arg1	methods					452:458	alcohol precipitation methods	430:458	alcohol precipitation methods	430:458	The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods.
29805493	9	67	theme	SCP	1092:1094	arg1	groups					1096:1101	the model and SCP groups	1078:1101	groups	1096:1101	Subsequently, the mice in the model and SCP groups were intraperitoneally injected with Cyp (20 mg/kg) once a day for 5 days.
29805493	5	68	theme	total	465:469	arg1	carbohydrate					471:482	total carbohydrate	465:482	total carbohydrate	465:482	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	15	69	theme	hypofunction	1916:1927	arg1	prevention					1895:1904	the prevention	1891:1904	the prevention of immune hypofunction	1891:1927	The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.
29805493	4	70	theme	Schisandra	361:370	arg1	SCP					388:390	SCP	388:390	SCP	388:390	The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods.
29805493	4	70	theme	Schisandra	361:370	arg1	polysaccharide					372:385	The crude Schisandra polysaccharide	351:385	The crude Schisandra polysaccharide (SCP)	351:391	The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods.
29805493	10	71	dep	thymus	1239:1244	arg1	indexes					1257:1263	indexes	1257:1263	indexes	1257:1263	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	5	72	theme	carbohydrate	471:482	arg1	contents					509:516	The total carbohydrate, uronic acid and protein contents	461:516	The total carbohydrate, uronic acid and protein contents	461:516	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	9	73	from	mice	1070:1073	arg1	groups					1096:1101	the model and SCP groups	1078:1101	groups	1096:1101	Subsequently, the mice in the model and SCP groups were intraperitoneally injected with Cyp (20 mg/kg) once a day for 5 days.
29805493	5	74	theme	phenol-sulfuric	544:558	arg1	method					597:602	the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method	540:602	method	597:602	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	1	75	theme	cyclophosphamide	175:190	arg1	effects					164:170	the well-known immunosuppressant effects	131:170	the well-known immunosuppressant effects of cyclophosphamide (Cyp)	131:196	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	6	76	theme	liquid	692:697	arg1	chromatography					699:712	high-performance liquid chromatography	675:712	high-performance liquid chromatography	675:712	The monosaccharide composition of SCP was determined by high-performance liquid chromatography.
29805493	1	77	theme	fruit	265:269	arg1	extract					250:256	the polysaccharide extract	231:256	the polysaccharide extract of the fruit of Schisandra chinensis	231:293	As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.)
29805493	10	78	theme	macrophages	1313:1323	arg1	function					1301:1308	the phagocytic function	1286:1308	the phagocytic function of macrophages	1286:1323	The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test.
29805493	14	79	theme	lymphocytes	1676:1686	arg1	rate					1660:1663	The apoptotic rate	1646:1663	The apoptotic rate of splenic lymphocytes	1646:1686	The apoptotic rate of splenic lymphocytes was determined by flow cytometric analysis.
29805493	5	80	theme	acid	560:563	arg1	method					597:602	the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method	540:602	method	597:602	The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively.
29805493	6	81	theme	high-performance	675:690	arg1	chromatography					699:712	high-performance liquid chromatography	675:712	high-performance liquid chromatography	675:712	The monosaccharide composition of SCP was determined by high-performance liquid chromatography.
29805493	7	82	theme	mg/10	785:789	arg1	SCP					776:778	low-dose SCP	767:778	low-dose SCP (0.4 mg/10 g)	767:792	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
29805493	7	82	theme	mg/10	785:789	arg1	g					791:791	0.4 mg/10 g	781:791	0.4 mg/10 g	781:791	ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups.
31781142	6	0	theme	expressed	918:926	arg1	genes					928:932	the differentially expressed genes	899:932	the differentially expressed genes	899:932	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	6	1	theme	wall	1081:1084	arg1	proteins					1086:1093	cell wall proteins	1076:1093	cell wall proteins	1076:1093	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	4	2	theme	transcriptional	532:546	arg1	network					548:554	the complex transcriptional network	520:554	the complex transcriptional network underlying wood development	520:582	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	10	3	theme	cell	1871:1874	arg1	formation					1881:1889	cell wall formation	1871:1889	cell wall formation	1871:1889	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	5	4	theme	comparative	623:633	arg1	description					635:645	a detailed comparative description	612:645	a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems	612:812	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	10	5	theme	comprehensive	1679:1691	arg1	analysis					1693:1700	the first comprehensive analysis	1669:1700	the first comprehensive analysis	1669:1700	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	5	theme	comprehensive	1679:1691	arg1	study					1660:1664	Our study	1656:1664	Our study	1656:1664	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	0	6	dep	trichocarpa	64:74	arg1	Torr					77:80	Torr	77:80	Torr	77:80	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	2	7	theme	gene	106:109	arg1	expression					111:120	gene expression	106:120	gene expression	106:120	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	2	8	theme	wood	207:210	arg1	quality					212:218	wood quality	207:218	wood quality	207:218	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	6	9	theme	many	962:965	arg1	mechanisms					979:988	many fundamental mechanisms	962:988	many fundamental mechanisms	962:988	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	10	10	theme	different	1930:1938	arg1	organs					1946:1951	different plant organs	1930:1951	different plant organs	1930:1951	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	11	from	xylogenesis	1915:1925	arg1	organs					1946:1951	different plant organs	1930:1951	different plant organs	1930:1951	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	4	12	theme	new	396:398	arg1	varieties					400:408	new varieties	396:408	new varieties characterized by higher yield and better wood quality	396:462	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	5	13	theme	changes	654:660	arg1	description					635:645	a detailed comparative description	612:645	a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems	612:812	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	5	14	from	xylogenesis	755:765	arg1	stems					808:812	stems	808:812	stems	808:812	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	5	14	from	xylogenesis	755:765	arg1	roots					798:802	Populus trichocarpa pioneer roots	770:802	Populus trichocarpa pioneer roots	770:802	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	2	15	theme	species	165:171	arg1	genetics					144:151	the genetics	140:151	the genetics of the tree species	140:171	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	7	16	theme	increasing	1267:1276	arg1	pectins					1342:1348	pectins	1342:1348	pectins	1342:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	16	theme	increasing	1267:1276	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	16	theme	increasing	1267:1276	arg1	amount					1278:1283	an increasing amount	1264:1283	an increasing amount of xylose building secondary cell wall hemicellulose and pectins	1264:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	9	17	from	dominant	1589:1596	arg1	stems					1601:1605	stems	1601:1605	stems	1601:1605	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	8	18	theme	cell	1470:1473	arg1	lignification					1480:1492	cell wall lignification	1470:1492	cell wall lignification	1470:1492	While hemicellulose degradation was typical for stems, possibly due to the intensive level of cell wall lignification.
31781142	7	19	theme	pectins	1342:1348	arg1	pectins					1342:1348	pectins	1342:1348	pectins	1342:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	19	theme	pectins	1342:1348	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	19	theme	pectins	1342:1348	arg1	amount					1278:1283	an increasing amount	1264:1283	an increasing amount of xylose building secondary cell wall hemicellulose and pectins	1264:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	2	20	theme	major	179:183	arg1	factor					185:190	a major factor	177:190	a major factor in determining wood quality	177:218	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	2	20	theme	major	179:183	arg1	Regulation					92:101	Regulation	92:101	Regulation	92:101	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	9	21	theme	main	1508:1511	arg1	units					1556:1560	guiacyl units	1548:1560	guiacyl units	1548:1560	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	9	21	theme	main	1508:1511	arg1	component					1513:1521	the main component	1504:1521	the main component of lignins in roots	1504:1541	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	9	22	from	roots	1537:1541	arg1	units					1556:1560	guiacyl units	1548:1560	guiacyl units	1548:1560	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	9	22	from	roots	1537:1541	arg1	component					1513:1521	the main component	1504:1521	the main component of lignins in roots	1504:1541	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	3	23	theme	genes	254:258	arg1	identification					236:249	the identification	232:249	the identification of genes that play a role in xylogenesis	232:290	Therefore, the identification of genes that play a role in xylogenesis is extremely important for understanding the mechanisms shaping the plant phenotype.
31781142	3	23	theme	genes	254:258	arg1	important					305:313	important	305:313	important	305:313	Therefore, the identification of genes that play a role in xylogenesis is extremely important for understanding the mechanisms shaping the plant phenotype.
31781142	8	24	theme	lignification	1480:1492	arg1	level					1461:1465	the intensive level	1447:1465	the intensive level of cell wall lignification	1447:1492	While hemicellulose degradation was typical for stems, possibly due to the intensive level of cell wall lignification.
31781142	0	25	theme	Populus	56:62	arg1	trichocarpa					64:74	Populus trichocarpa	56:74	Populus trichocarpa (Torr	56:80	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	9	26	from	lignins	1526:1532	arg1	roots					1537:1541	roots	1537:1541	roots	1537:1541	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	4	27	theme	wood	451:454	arg1	quality					456:462	better wood quality	444:462	better wood quality	444:462	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	10	28	from	under-	1760:1765	arg1	analysis					1693:1700	the first comprehensive analysis	1669:1700	the first comprehensive analysis	1669:1700	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	28	from	under-	1760:1765	arg1	study					1660:1664	Our study	1656:1664	Our study	1656:1664	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	6	29	theme	genes	1038:1042	arg1	expression					1024:1033	expression	1024:1033	expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins	1024:1123	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	5	30	theme	cell-wall-related	720:736	arg1	compounds					738:746	cell-wall-related compounds	720:746	cell-wall-related compounds	720:746	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	7	31	theme	chromatography	1130:1143	arg1	spectrometry					1165:1176	Gas chromatography time-of-flight mass spectrometry	1126:1176	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)	1126:1188	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	31	theme	chromatography	1130:1143	arg1	GC-TOF-MS					1179:1187	GC-TOF-MS	1179:1187	GC-TOF-MS	1179:1187	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	4	32	theme	higher	427:432	arg1	yield					434:438	higher yield	427:438	higher yield	427:438	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	5	33	theme	compounds	738:746	arg1	transcription					682:694	transcription	682:694	transcription	682:694	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	5	33	theme	compounds	738:746	arg1	biosynthesis					704:715	the biosynthesis	700:715	the biosynthesis	700:715	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	3	34	theme	plant	360:364	arg1	phenotype					366:374	the plant phenotype	356:374	the plant phenotype	356:374	Therefore, the identification of genes that play a role in xylogenesis is extremely important for understanding the mechanisms shaping the plant phenotype.
31781142	0	35	theme	Xylem	0:4	arg1	Formation					16:24	Xylem Cell Wall Formation	0:24	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.	0:81	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	10	36	from	parts	1788:1792	arg1	analysis					1693:1700	the first comprehensive analysis	1669:1700	the first comprehensive analysis	1669:1700	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	36	from	parts	1788:1792	arg1	study					1660:1664	Our study	1656:1664	Our study	1656:1664	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	7	37	theme	wall	1319:1322	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	0	38	theme	Wall	11:14	arg1	Formation					16:24	Xylem Cell Wall Formation	0:24	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.	0:81	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	1	39	theme	&	83:83	arg1	Gray					85:88	& Gray	83:88	& Gray	83:88	& Gray).
31781142	7	40	theme	secondary	1304:1312	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	5	41	theme	trichocarpa	778:788	arg1	roots					798:802	Populus trichocarpa pioneer roots	770:802	Populus trichocarpa pioneer roots	770:802	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	7	42	theme	time-of-flight	1145:1158	arg1	spectrometry					1165:1176	Gas chromatography time-of-flight mass spectrometry	1126:1176	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)	1126:1188	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	42	theme	time-of-flight	1145:1158	arg1	GC-TOF-MS					1179:1187	GC-TOF-MS	1179:1187	GC-TOF-MS	1179:1187	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	6	43	theme	expression	1024:1033	arg1	pattern					1013:1019	the pattern	1009:1019	e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins	1004:1123	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	10	44	theme	first	1673:1677	arg1	analysis					1693:1700	the first comprehensive analysis	1669:1700	the first comprehensive analysis	1669:1700	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	44	theme	first	1673:1677	arg1	study					1660:1664	Our study	1656:1664	Our study	1656:1664	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	7	45	theme	Gas	1126:1128	arg1	spectrometry					1165:1176	Gas chromatography time-of-flight mass spectrometry	1126:1176	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)	1126:1188	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	45	theme	Gas	1126:1128	arg1	GC-TOF-MS					1179:1187	GC-TOF-MS	1179:1187	GC-TOF-MS	1179:1187	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	0	46	from	Formation	16:24	arg1	Stems					47:51	Stems	47:51	Stems	47:51	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	0	46	from	Formation	16:24	arg1	Roots					37:41	Pioneer Roots	29:41	Pioneer Roots	29:41	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	6	47	theme	microarray	838:847	arg1	analysis					849:856	microarray analysis	838:856	microarray analysis	838:856	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	10	48	theme	tree	1783:1786	arg1	parts					1788:1792	aboveground tree parts	1771:1792	aboveground tree parts	1771:1792	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	49	theme	molecular	1839:1847	arg1	mechanisms					1849:1858	molecular mechanisms	1839:1858	molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs	1839:1951	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	4	50	dep	Efforts	377:383	arg1	develop					388:394	develop	388:394	to develop new varieties characterized by higher yield and better wood quality	385:462	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	6	51	theme	polysaccharides	1096:1110	arg1	biosynthesis					1060:1071	the biosynthesis	1056:1071	the biosynthesis of cell wall proteins, polysaccharides, and lignins	1056:1123	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	4	52	theme	wood	567:570	arg1	development					572:582	wood development	567:582	wood development	567:582	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	7	53	theme	xylose	1288:1293	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	6	54	theme	genes	928:932	arg1	%					894:894	only approximately 10%	873:894	only approximately 10% of the differentially expressed genes	873:932	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	6	54	theme	genes	928:932	arg1	genes					928:932	the differentially expressed genes	899:932	the differentially expressed genes	899:932	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	6	55	theme	proteins	1086:1093	arg1	biosynthesis					1060:1071	the biosynthesis	1056:1071	the biosynthesis of cell wall proteins, polysaccharides, and lignins	1056:1123	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	10	56	theme	wall	1876:1879	arg1	formation					1881:1889	cell wall formation	1871:1889	cell wall formation	1871:1889	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	5	57	theme	detailed	614:621	arg1	description					635:645	a detailed comparative description	612:645	a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems	612:812	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	9	58	from	component	1513:1521	arg1	roots					1537:1541	roots	1537:1541	roots	1537:1541	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	6	59	theme	cell	1076:1079	arg1	proteins					1086:1093	cell wall proteins	1076:1093	cell wall proteins	1076:1093	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	4	60	theme	complex	524:530	arg1	network					548:554	the complex transcriptional network	520:554	the complex transcriptional network underlying wood development	520:582	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	7	61	with	similar	1250:1256	arg1	pectins					1342:1348	pectins	1342:1348	pectins	1342:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	61	with	similar	1250:1256	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	61	with	similar	1250:1256	arg1	amount					1278:1283	an increasing amount	1264:1283	an increasing amount of xylose building secondary cell wall hemicellulose and pectins	1264:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	10	62	theme	molecular	1725:1733	arg1	level					1735:1739	the structural and molecular level	1706:1739	the structural and molecular level	1706:1739	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	7	63	from	similar	1250:1256	arg1	stems					1369:1373	the stems	1365:1373	the stems	1365:1373	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	2	64	theme	expression	111:120	arg1	factor					185:190	a major factor	177:190	a major factor in determining wood quality	177:218	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	2	64	theme	expression	111:120	arg1	Regulation					92:101	Regulation	92:101	Regulation	92:101	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	5	65	theme	present	589:595	arg1	study					597:601	The present study	585:601	The present study	585:601	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	10	66	theme	structural	1710:1719	arg1	level					1735:1739	the structural and molecular level	1706:1739	the structural and molecular level	1706:1739	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	67	from	analysis	1693:1700	arg1	parts					1788:1792	aboveground tree parts	1771:1792	aboveground tree parts	1771:1792	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	67	from	analysis	1693:1700	arg1	under-					1760:1765	under-	1760:1765	under-	1760:1765	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	68	theme	xylogenesis	1745:1755	arg1	analysis					1693:1700	the first comprehensive analysis	1669:1700	the first comprehensive analysis	1669:1700	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	68	theme	xylogenesis	1745:1755	arg1	study					1660:1664	Our study	1656:1664	Our study	1656:1664	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	6	69	theme	fundamental	967:977	arg1	mechanisms					979:988	many fundamental mechanisms	962:988	many fundamental mechanisms	962:988	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	10	70	theme	mechanisms	1849:1858	arg1	complexity					1825:1834	the great complexity	1815:1834	the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs	1815:1951	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	71	theme	plant	1940:1944	arg1	organs					1946:1951	different plant organs	1930:1951	different plant organs	1930:1951	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	6	72	dep	Even	815:818	arg1	indicated					858:866	indicated	858:866	indicated that only approximately 10% of the differentially expressed genes were common to both organs	858:959	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	10	73	from	xylogenesis	1745:1755	arg1	parts					1788:1792	aboveground tree parts	1771:1792	aboveground tree parts	1771:1792	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	73	from	xylogenesis	1745:1755	arg1	under-					1760:1765	under-	1760:1765	under-	1760:1765	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	74	theme	aboveground	1771:1781	arg1	parts					1788:1792	aboveground tree parts	1771:1792	aboveground tree parts	1771:1792	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	8	75	theme	intensive	1451:1459	arg1	level					1461:1465	the intensive level	1447:1465	the intensive level of cell wall lignification	1447:1492	While hemicellulose degradation was typical for stems, possibly due to the intensive level of cell wall lignification.
31781142	0	76	theme	Pioneer	29:35	arg1	Roots					37:41	Pioneer Roots	29:41	Pioneer Roots	29:41	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	8	77	theme	wall	1475:1478	arg1	lignification					1480:1492	cell wall lignification	1470:1492	cell wall lignification	1470:1492	While hemicellulose degradation was typical for stems, possibly due to the intensive level of cell wall lignification.
31781142	7	78	theme	monosaccharides	1220:1234	arg1	similar					1250:1256	similar	1250:1256	similar	1250:1256	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	78	theme	monosaccharides	1220:1234	arg1	composition					1205:1215	the composition	1201:1215	the composition of monosaccharides	1201:1234	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	8	79	dep	typical	1412:1418	arg1	While					1376:1380	While	1376:1380	While	1376:1380	While hemicellulose degradation was typical for stems, possibly due to the intensive level of cell wall lignification.
31781142	4	80	theme	better	444:449	arg1	quality					456:462	better wood quality	444:462	better wood quality	444:462	Efforts to develop new varieties characterized by higher yield and better wood quality will greatly benefit from recognizing and understanding the complex transcriptional network underlying wood development.
31781142	0	81	theme	trichocarpa	64:74	arg1	Formation					16:24	Xylem Cell Wall Formation	0:24	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.	0:81	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	10	82	from	level	1735:1739	arg1	analysis					1693:1700	the first comprehensive analysis	1669:1700	the first comprehensive analysis	1669:1700	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	10	82	from	level	1735:1739	arg1	study					1660:1664	Our study	1656:1664	Our study	1656:1664	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	9	83	theme	lignins	1526:1532	arg1	units					1556:1560	guiacyl units	1548:1560	guiacyl units	1548:1560	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	9	83	theme	lignins	1526:1532	arg1	component					1513:1521	the main component	1504:1521	the main component of lignins in roots	1504:1541	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	7	84	theme	hemicellulose	1324:1336	arg1	pectins					1342:1348	pectins	1342:1348	pectins	1342:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	84	theme	hemicellulose	1324:1336	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	84	theme	hemicellulose	1324:1336	arg1	amount					1278:1283	an increasing amount	1264:1283	an increasing amount of xylose building secondary cell wall hemicellulose and pectins	1264:1348	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	3	85	dep	mechanisms	337:346	arg1	shaping					348:354	shaping	348:354	shaping	348:354	Therefore, the identification of genes that play a role in xylogenesis is extremely important for understanding the mechanisms shaping the plant phenotype.
31781142	0	86	theme	Cell	6:9	arg1	Formation					16:24	Xylem Cell Wall Formation	0:24	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.	0:81	Xylem Cell Wall Formation in Pioneer Roots and Stems of Populus trichocarpa (Torr.
31781142	9	87	theme	guiacyl	1548:1554	arg1	units					1556:1560	guiacyl units	1548:1560	guiacyl units	1548:1560	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	9	87	theme	guiacyl	1548:1554	arg1	component					1513:1521	the main component	1504:1521	the main component of lignins in roots	1504:1541	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	9	88	from	stems	1601:1605	arg1	dominant					1589:1596	dominant	1589:1596	dominant	1589:1596	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	7	89	theme	cell	1314:1317	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	90	theme	mass	1160:1163	arg1	spectrometry					1165:1176	Gas chromatography time-of-flight mass spectrometry	1126:1176	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)	1126:1188	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	90	theme	mass	1160:1163	arg1	GC-TOF-MS					1179:1187	GC-TOF-MS	1179:1187	GC-TOF-MS	1179:1187	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	91	from	stems	1369:1373	arg1	similar					1250:1256	similar	1250:1256	similar	1250:1256	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	91	from	stems	1369:1373	arg1	composition					1205:1215	the composition	1201:1215	the composition of monosaccharides	1201:1234	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	7	92	theme	building	1295:1302	arg1	hemicellulose					1324:1336	xylose building secondary cell wall hemicellulose	1288:1336	xylose building secondary cell wall hemicellulose	1288:1336	Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) shows that the composition of monosaccharides was also very similar, with an increasing amount of xylose building secondary cell wall hemicellulose and pectins, especially in the stems.
31781142	10	93	theme	great	1819:1823	arg1	complexity					1825:1834	the great complexity	1815:1834	the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs	1815:1951	Our study is the first comprehensive analysis, at the structural and molecular level, of xylogenesis in under- and aboveground tree parts, and clearly reveals the great complexity of molecular mechanisms underlying cell wall formation and modification during xylogenesis in different plant organs.
31781142	5	94	theme	Populus	770:776	arg1	roots					798:802	Populus trichocarpa pioneer roots	770:802	Populus trichocarpa pioneer roots	770:802	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	9	95	theme	syringyl	1569:1576	arg1	units					1578:1582	syringyl units	1569:1582	syringyl units	1569:1582	Notably, the main component of lignins in roots were guiacyl units, while syringyl units were dominant in stems, where fibers are especially needed for support.
31781142	8	96	theme	hemicellulose	1382:1394	arg1	degradation					1396:1406	hemicellulose degradation	1382:1406	hemicellulose degradation	1382:1406	While hemicellulose degradation was typical for stems, possibly due to the intensive level of cell wall lignification.
31781142	5	97	theme	pioneer	790:796	arg1	roots					798:802	Populus trichocarpa pioneer roots	770:802	Populus trichocarpa pioneer roots	770:802	The present study provides a detailed comparative description of the changes that occur in genes transcription and the biosynthesis of cell-wall-related compounds during xylogenesis in Populus trichocarpa pioneer roots and stems.
31781142	6	98	theme	analysis	849:856	arg1	results					827:833	results	827:833	results of microarray analysis	827:856	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	6	99	theme	lignins	1117:1123	arg1	biosynthesis					1060:1071	the biosynthesis	1056:1071	the biosynthesis of cell wall proteins, polysaccharides, and lignins	1056:1123	Even though results of microarray analysis indicated that only approximately 10% of the differentially expressed genes were common to both organs, many fundamental mechanisms were similar; e.g. the pattern of expression of genes involved in the biosynthesis of cell wall proteins, polysaccharides, and lignins.
31781142	2	100	dep	Regulation	92:101	arg1	determined					126:135	determined	126:135	determined by the genetics of the tree species	126:171	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
31781142	2	101	theme	tree	160:163	arg1	species					165:171	the tree species	156:171	the tree species	156:171	Regulation of gene expression, as determined by the genetics of the tree species, is a major factor in determining wood quality.
30471266	6	0	theme	columnar	832:839	arg1	ACCs					848:851	ACCs	848:851	ACCs	848:851	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	0	theme	columnar	832:839	arg1	cells					841:845	4 axial columnar cells	824:845	4 axial columnar cells (ACCs)	824:852	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	14	1	theme	larva	1983:1987	arg1	region					1963:1968	the anterior ('new head') region	1937:1968	the anterior ('new head') region of the Ciona larva	1937:1987	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	5	2	theme	confocal	681:688	arg1	imaging					690:696	confocal imaging	681:696	confocal imaging	681:696	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	12	3	theme	larval	1770:1775	arg1	attachment					1777:1786	larval attachment	1770:1786	larval attachment	1770:1786	Consistently, carbohydrate specific lectins label the papillar apex, the granules within CCs and the adhesive plaques upon larval attachment.
30471266	8	4	theme	role	1228:1231	arg1	indicative					1199:1208	indicative	1199:1208	indicative	1199:1208	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	10	5	theme	granules	1409:1416	arg1	microvilli					1332:1341	microvilli	1332:1341	microvilli	1332:1341	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	10	5	theme	granules	1409:1416	arg1	numbers					1389:1395	a large numbers	1381:1395	a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins	1381:1494	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	10	5	theme	granules	1409:1416	arg1	vesicles					1360:1367	small endocytic vesicles	1344:1367	small endocytic vesicles	1344:1367	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	2	6	theme	papillae	260:267	arg1	importance					246:255	the importance	242:255	the importance of papillae for the ascidian development	242:296	Despite the importance of papillae for the ascidian development, their cellular composition is only roughly described.
30471266	8	7	theme	neuroactive	1164:1174	arg1	vesicles					1190:1197	neuroactive and endocytic vesicles	1164:1197	neuroactive and endocytic vesicles indicative of a chemosensory role	1164:1231	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	6	8	theme	sensory	873:879	arg1	PSNs					890:893	PSNs	890:893	PSNs	890:893	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	8	theme	sensory	873:879	arg1	neurons					881:887	4 lateral primary sensory neurons	855:887	4 lateral primary sensory neurons (PSNs)	855:894	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	5	9	theme	serial-section	642:655	arg1	microscopy					666:675	serial-section electron microscopy	642:675	serial-section electron microscopy	642:675	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	11	10	theme	collocyte	1545:1553	arg1	granules					1555:1562	collocyte granules	1545:1562	collocyte granules	1545:1562	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	8	11	theme	endocytic	1180:1188	arg1	vesicles					1190:1197	neuroactive and endocytic vesicles	1164:1197	neuroactive and endocytic vesicles indicative of a chemosensory role	1164:1231	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	10	12	theme	large	1383:1387	arg1	numbers					1389:1395	a large numbers	1381:1395	a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins	1381:1494	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	8	13	theme	indicative	1199:1208	arg1	vesicles					1190:1197	neuroactive and endocytic vesicles	1164:1197	neuroactive and endocytic vesicles indicative of a chemosensory role	1164:1231	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	14	14	dep	anterior	1941:1948	arg1	head					1956:1959	'new head'	1951:1960	'new head'	1951:1960	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	7	15	theme	novel	987:991	arg1	ones					993:996	novel ones	987:996	novel ones for collocytes	987:1011	We propose molecular markers for each cell type including novel ones for collocytes.
30471266	11	16	theme	polysaccharides	1630:1644	arg1	types					1536:1540	two different types	1522:1540	two different types of collocyte granules	1522:1562	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	16	theme	polysaccharides	1630:1644	arg1	quantities					1616:1625	larger quantities	1609:1625	larger quantities of polysaccharides	1609:1644	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	10	17	contain	contain	1474:1480	arg2	glycoproteins					1482:1494	glycoproteins	1482:1494	glycoproteins	1482:1494	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	10	17	contain	contain	1474:1480	arg1	granules					1409:1416	adhesive granules	1400:1416	adhesive granules that, according to element analysis and histochemistry, contain glycoproteins	1400:1494	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	11	18	contain	containing	1577:1586	arg1	types					1536:1540	two different types	1522:1540	two different types of collocyte granules	1522:1562	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	18	contain	containing	1577:1586	arg1	them					1572:1575	them	1572:1575	them	1572:1575	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	18	contain	containing	1577:1586	arg2	material					1596:1603	fibrous material	1588:1603	fibrous material	1588:1603	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	18	contain	containing	1577:1586	arg1	one					1565:1567	one	1565:1567	one	1565:1567	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	5	19	theme	marker	711:716	arg1	combinations					718:729	various marker combinations	703:729	various marker combinations	703:729	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	1	20	theme	sensory	121:127	arg1	organ					138:142	a transient sensory adhesive organ	109:142	a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult	109:231	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	8	21	from	role	1070:1073	arg1	function					1087:1094	papillar function	1078:1094	papillar function	1078:1094	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	5	22	theme	papillae	776:783	arg1	organization					750:761	the 3D organization	743:761	the 3D organization of the Ciona papillae	743:783	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	14	23	contain	has	2036:2038	arg1	cells					2024:2028	the adhesive secreting cells	2001:2028	the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution	2001:2113	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	14	23	contain	has	2036:2038	arg2	implications					2040:2051	implications	2040:2051	implications for developmental biology, cell differentiation and evolution	2040:2113	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	9	24	theme	glutamatergic	1278:1290	arg1	PSNs					1292:1295	the ciliated glutamatergic PSNs	1265:1295	the ciliated glutamatergic PSNs	1265:1295	They are clearly distinct from the ciliated glutamatergic PSNs.
30471266	12	25	theme	carbohydrate	1661:1672	arg1	lectins					1683:1689	carbohydrate specific lectins	1661:1689	carbohydrate specific lectins	1661:1689	Consistently, carbohydrate specific lectins label the papillar apex, the granules within CCs and the adhesive plaques upon larval attachment.
30471266	3	26	theme	molecular	439:447	arg1	markers					449:455	discriminative molecular markers	424:455	discriminative molecular markers	424:455	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	8	27	theme	subcellular	1018:1028	arg1	characteristics					1030:1044	The subcellular characteristics	1014:1044	The subcellular characteristics	1014:1044	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	8	27	theme	subcellular	1018:1028	arg1	suggestive					1050:1059	suggestive	1050:1059	suggestive	1050:1059	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	1	28	theme	Ascidian	72:79	arg1	palps					91:95	Ascidian papillae (palps)	72:96	Ascidian papillae (palps)	72:96	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	14	29	theme	cell	2080:2083	arg1	differentiation					2085:2099	cell differentiation	2080:2099	cell differentiation	2080:2099	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	0	30	theme	collocytes	60:69	arg1	nature					27:32	the nature	23:32	the nature of the adhesive secreting collocytes	23:69	Papillae revisited and the nature of the adhesive secreting collocytes.
30471266	14	31	theme	Ciona	1977:1981	arg1	larva					1983:1987	the Ciona larva	1973:1987	the Ciona larva	1973:1987	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	13	32	theme	evolutionary	1830:1841	arg1	type					1871:1874	an evolutionary ancient neurosecretory cell type	1827:1874	an evolutionary ancient neurosecretory cell type	1827:1874	We further propose CCs to derive from an evolutionary ancient neurosecretory cell type.
30471266	3	33	theme	different	465:473	arg1	types					480:484	the different cell types	461:484	the different cell types	461:484	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	10	34	contain	contain	1324:1330	arg2	vesicles					1360:1367	small endocytic vesicles	1344:1367	small endocytic vesicles	1344:1367	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	10	34	contain	contain	1324:1330	arg1	CCs					1298:1300	CCs	1298:1300	CCs	1298:1300	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	10	34	contain	contain	1324:1330	arg2	microvilli					1332:1341	microvilli	1332:1341	microvilli	1332:1341	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	10	34	contain	contain	1324:1330	arg2	numbers					1389:1395	a large numbers	1381:1395	a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins	1381:1494	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	6	35	theme	primary	865:871	arg1	PSNs					890:893	PSNs	890:893	PSNs	890:893	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	35	theme	primary	865:871	arg1	neurons					881:887	4 lateral primary sensory neurons	855:887	4 lateral primary sensory neurons (PSNs)	855:894	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	3	36	theme	cell	407:410	arg1	numbers					412:418	cell numbers	407:418	cell numbers	407:418	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	13	37	theme	neurosecretory	1851:1864	arg1	type					1871:1874	an evolutionary ancient neurosecretory cell type	1827:1874	an evolutionary ancient neurosecretory cell type	1827:1874	We further propose CCs to derive from an evolutionary ancient neurosecretory cell type.
30471266	8	38	theme	role	1070:1073	arg1	characteristics					1030:1044	The subcellular characteristics	1014:1044	The subcellular characteristics	1014:1044	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	8	38	theme	role	1070:1073	arg1	suggestive					1050:1059	suggestive	1050:1059	suggestive	1050:1059	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	0	39	theme	secreting	50:58	arg1	collocytes					60:69	the adhesive secreting collocytes	37:69	the adhesive secreting collocytes	37:69	Papillae revisited and the nature of the adhesive secreting collocytes.
30471266	11	40	theme	fibrous	1588:1594	arg1	material					1596:1603	fibrous material	1588:1603	fibrous material	1588:1603	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	8	41	theme	papillar	1078:1085	arg1	function					1087:1094	papillar function	1078:1094	papillar function	1078:1094	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	4	42	theme	neural	532:537	arg1	types					544:548	neural cell types	532:548	neural cell types	532:548	While some attention was given to neural cell types and their connectivity little is known about the adhesive producing collocytes.
30471266	11	43	theme	them	1572:1575	arg1	types					1536:1540	two different types	1522:1540	two different types of collocyte granules	1522:1562	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	43	theme	them	1572:1575	arg1	them					1572:1575	them	1572:1575	them	1572:1575	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	43	theme	them	1572:1575	arg1	one					1565:1567	one	1565:1567	one	1565:1567	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	0	44	dep	and	19:21	arg1	nature					27:32	the nature	23:32	the nature of the adhesive secreting collocytes	23:69	Papillae revisited and the nature of the adhesive secreting collocytes.
30471266	10	45	theme	endocytic	1350:1358	arg1	vesicles					1360:1367	small endocytic vesicles	1344:1367	small endocytic vesicles	1344:1367	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	6	46	theme	central	903:909	arg1	CCs					923:925	CCs	923:925	CCs	923:925	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	46	theme	central	903:909	arg1	collocytes					911:920	12 central collocytes	900:920	12 central collocytes (CCs)	900:926	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	14	47	theme	anterior	1941:1948	arg1	region					1963:1968	the anterior ('new head') region	1937:1968	the anterior ('new head') region of the Ciona larva	1937:1987	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	4	48	theme	producing	608:616	arg1	collocytes					618:627	the adhesive producing collocytes	595:627	the adhesive producing collocytes	595:627	While some attention was given to neural cell types and their connectivity little is known about the adhesive producing collocytes.
30471266	5	49	theme	electron	657:664	arg1	microscopy					666:675	serial-section electron microscopy	642:675	serial-section electron microscopy	642:675	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	8	50	theme	apical	1116:1121	arg1	protrusions					1123:1133	apical protrusions	1116:1133	apical protrusions	1116:1133	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	5	51	with	microscopy	666:675	arg1	combinations					718:729	various marker combinations	703:729	various marker combinations	703:729	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	4	52	theme	little	573:578	arg1	connectivity					560:571	their connectivity	554:571	their connectivity little	554:578	While some attention was given to neural cell types and their connectivity little is known about the adhesive producing collocytes.
30471266	10	53	theme	adhesive	1400:1407	arg1	granules					1409:1416	adhesive granules	1400:1416	adhesive granules that, according to element analysis and histochemistry, contain glycoproteins	1400:1494	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	6	54	theme	axial	826:830	arg1	ACCs					848:851	ACCs	848:851	ACCs	848:851	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	54	theme	axial	826:830	arg1	cells					841:845	4 axial columnar cells	824:845	4 axial columnar cells (ACCs)	824:852	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	2	55	theme	ascidian	277:284	arg1	development					286:296	the ascidian development	273:296	the ascidian development	273:296	Despite the importance of papillae for the ascidian development, their cellular composition is only roughly described.
30471266	11	56	theme	different	1526:1534	arg1	types					1536:1540	two different types	1522:1540	two different types of collocyte granules	1522:1562	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	56	theme	different	1526:1534	arg1	one					1565:1567	one	1565:1567	one	1565:1567	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	56	theme	different	1526:1534	arg1	them					1572:1575	them	1572:1575	them	1572:1575	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	56	theme	different	1526:1534	arg1	quantities					1616:1625	larger quantities	1609:1625	larger quantities of polysaccharides	1609:1644	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	1	57	theme	larval	157:162	arg1	settlement					164:173	larval settlement	157:173	larval settlement	157:173	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	8	58	theme	chemosensory	1215:1226	arg1	role					1228:1231	a chemosensory role	1213:1231	a chemosensory role	1213:1231	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	6	59	theme	papillar	798:805	arg1	development					807:817	the papillar development	794:817	the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs)	794:926	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	2	60	theme	cellular	305:312	arg1	composition					314:324	their cellular composition	299:324	their cellular composition	299:324	Despite the importance of papillae for the ascidian development, their cellular composition is only roughly described.
30471266	12	61	theme	adhesive	1748:1755	arg1	plaques					1757:1763	the adhesive plaques	1744:1763	the adhesive plaques upon larval attachment	1744:1786	Consistently, carbohydrate specific lectins label the papillar apex, the granules within CCs and the adhesive plaques upon larval attachment.
30471266	10	62	gly	glycoproteins	1482:1494	arg1	glycoproteins					1482:1494	glycoproteins	1482:1494	glycoproteins	1482:1494	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	11	63	theme	granules	1555:1562	arg1	types					1536:1540	two different types	1522:1540	two different types of collocyte granules	1522:1562	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	63	theme	granules	1555:1562	arg1	one					1565:1567	one	1565:1567	one	1565:1567	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	63	theme	granules	1555:1562	arg1	them					1572:1575	them	1572:1575	them	1572:1575	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	63	theme	granules	1555:1562	arg1	quantities					1616:1625	larger quantities	1609:1625	larger quantities of polysaccharides	1609:1644	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	1	64	theme	metamorphosis	192:204	arg1	settlement					164:173	larval settlement	157:173	larval settlement	157:173	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	1	64	theme	metamorphosis	192:204	arg1	onset					183:187	the onset	179:187	the onset of metamorphosis	179:204	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	9	65	from	PSNs	1292:1295	arg1	distinct					1251:1258	distinct	1251:1258	distinct	1251:1258	They are clearly distinct from the ciliated glutamatergic PSNs.
30471266	6	66	with	development	807:817	arg1	cells					841:845	4 axial columnar cells	824:845	4 axial columnar cells (ACCs)	824:852	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	66	with	development	807:817	arg1	ACCs					848:851	ACCs	848:851	ACCs	848:851	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	66	with	development	807:817	arg1	neurons					881:887	4 lateral primary sensory neurons	855:887	4 lateral primary sensory neurons (PSNs)	855:894	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	66	with	development	807:817	arg1	collocytes					911:920	12 central collocytes	900:920	12 central collocytes (CCs)	900:926	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	66	with	development	807:817	arg1	PSNs					890:893	PSNs	890:893	PSNs	890:893	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	66	with	development	807:817	arg1	CCs					923:925	CCs	923:925	CCs	923:925	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	5	67	theme	various	703:709	arg1	combinations					718:729	various marker combinations	703:729	various marker combinations	703:729	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	1	68	theme	transient	111:119	arg1	organ					138:142	a transient sensory adhesive organ	109:142	a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult	109:231	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	5	69	theme	Ciona	770:774	arg1	papillae					776:783	the Ciona papillae	766:783	the Ciona papillae	766:783	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	8	70	contain	contain	1156:1162	arg1	ACCs					1101:1104	the ACCs	1097:1104	the ACCs featuring apical protrusions and microvilli	1097:1148	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	8	70	contain	contain	1156:1162	arg2	vesicles					1190:1197	neuroactive and endocytic vesicles	1164:1197	neuroactive and endocytic vesicles indicative of a chemosensory role	1164:1231	The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role.
30471266	7	71	theme	cell	967:970	arg1	type					972:975	each cell type	962:975	each cell type	962:975	We propose molecular markers for each cell type including novel ones for collocytes.
30471266	1	72	theme	adhesive	129:136	arg1	organ					138:142	a transient sensory adhesive organ	109:142	a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult	109:231	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	9	73	theme	ciliated	1269:1276	arg1	PSNs					1292:1295	the ciliated glutamatergic PSNs	1265:1295	the ciliated glutamatergic PSNs	1265:1295	They are clearly distinct from the ciliated glutamatergic PSNs.
30471266	5	74	theme	3D	747:748	arg1	organization					750:761	the 3D organization	743:761	the 3D organization of the Ciona papillae	743:783	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	7	75	theme	molecular	940:948	arg1	markers					950:956	molecular markers	940:956	molecular markers for each cell type including novel ones for collocytes	940:1011	We propose molecular markers for each cell type including novel ones for collocytes.
30471266	7	75	theme	molecular	940:948	arg1	ones					993:996	novel ones	987:996	novel ones for collocytes	987:1011	We propose molecular markers for each cell type including novel ones for collocytes.
30471266	14	76	theme	adhesive	2005:2012	arg1	cells					2024:2028	the adhesive secreting cells	2001:2028	the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution	2001:2113	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	12	77	theme	papillar	1701:1708	arg1	apex					1710:1713	the papillar apex	1697:1713	the papillar apex	1697:1713	Consistently, carbohydrate specific lectins label the papillar apex, the granules within CCs and the adhesive plaques upon larval attachment.
30471266	3	78	theme	Ciona	357:361	arg1	intestinalis/robusta					363:382	Ciona intestinalis/robusta	357:382	Ciona intestinalis/robusta	357:382	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	13	79	theme	cell	1866:1869	arg1	type					1871:1874	an evolutionary ancient neurosecretory cell type	1827:1874	an evolutionary ancient neurosecretory cell type	1827:1874	We further propose CCs to derive from an evolutionary ancient neurosecretory cell type.
30471266	3	80	theme	markers	449:455	arg1	missing					489:495	missing	489:495	missing	489:495	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	3	80	theme	markers	449:455	arg1	definition					393:402	a clear definition	385:402	a clear definition of cell numbers and discriminative molecular markers for the different cell types	385:484	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	1	81	theme	papillae	81:88	arg1	palps					91:95	Ascidian papillae (palps)	72:96	Ascidian papillae (palps)	72:96	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	12	82	theme	specific	1674:1681	arg1	lectins					1683:1689	carbohydrate specific lectins	1661:1689	carbohydrate specific lectins	1661:1689	Consistently, carbohydrate specific lectins label the papillar apex, the granules within CCs and the adhesive plaques upon larval attachment.
30471266	5	83	with	imaging	690:696	arg1	combinations					718:729	various marker combinations	703:729	various marker combinations	703:729	We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae.
30471266	3	84	theme	clear	387:391	arg1	missing					489:495	missing	489:495	missing	489:495	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	3	84	theme	clear	387:391	arg1	definition					393:402	a clear definition	385:402	a clear definition of cell numbers and discriminative molecular markers for the different cell types	385:484	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	10	85	theme	element	1437:1443	arg1	analysis					1445:1452	element analysis	1437:1452	element analysis	1437:1452	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30471266	3	86	theme	discriminative	424:437	arg1	markers					449:455	discriminative molecular markers	424:455	discriminative molecular markers	424:455	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	14	87	theme	developmental	2057:2069	arg1	biology					2071:2077	developmental biology	2057:2077	developmental biology	2057:2077	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	13	88	theme	ancient	1843:1849	arg1	type					1871:1874	an evolutionary ancient neurosecretory cell type	1827:1874	an evolutionary ancient neurosecretory cell type	1827:1874	We further propose CCs to derive from an evolutionary ancient neurosecretory cell type.
30471266	3	89	theme	cell	475:478	arg1	types					480:484	the different cell types	461:484	the different cell types	461:484	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	6	90	theme	lateral	857:863	arg1	PSNs					890:893	PSNs	890:893	PSNs	890:893	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	6	90	theme	lateral	857:863	arg1	neurons					881:887	4 lateral primary sensory neurons	855:887	4 lateral primary sensory neurons (PSNs)	855:894	We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs).
30471266	14	91	theme	region	1963:1968	arg1	development					1922:1932	the development	1918:1932	the development of the anterior ('new head') region of the Ciona larva	1918:1987	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	14	91	theme	region	1963:1968	arg1	bioadhesion					2125:2135	bioadhesion	2125:2135	bioadhesion	2125:2135	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	14	91	theme	region	1963:1968	arg1	cells					2024:2028	the adhesive secreting cells	2001:2028	the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution	2001:2113	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	3	92	theme	numbers	412:418	arg1	missing					489:495	missing	489:495	missing	489:495	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	3	92	theme	numbers	412:418	arg1	definition					393:402	a clear definition	385:402	a clear definition of cell numbers and discriminative molecular markers for the different cell types	385:484	For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing.
30471266	0	93	theme	adhesive	41:48	arg1	collocytes					60:69	the adhesive secreting collocytes	37:69	the adhesive secreting collocytes	37:69	Papillae revisited and the nature of the adhesive secreting collocytes.
30471266	4	94	theme	cell	539:542	arg1	types					544:548	neural cell types	532:548	neural cell types	532:548	While some attention was given to neural cell types and their connectivity little is known about the adhesive producing collocytes.
30471266	14	95	theme	new	1952:1954	arg1	head					1956:1959	'new head'	1951:1960	'new head'	1951:1960	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	4	96	theme	adhesive	599:606	arg1	collocytes					618:627	the adhesive producing collocytes	595:627	the adhesive producing collocytes	595:627	While some attention was given to neural cell types and their connectivity little is known about the adhesive producing collocytes.
30471266	14	97	theme	secreting	2014:2022	arg1	cells					2024:2028	the adhesive secreting cells	2001:2028	the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution	2001:2113	Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.
30471266	11	98	theme	larger	1609:1614	arg1	types					1536:1540	two different types	1522:1540	two different types of collocyte granules	1522:1562	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	11	98	theme	larger	1609:1614	arg1	quantities					1616:1625	larger quantities	1609:1625	larger quantities of polysaccharides	1609:1644	Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides.
30471266	1	99	theme	filterfeeding	213:225	arg1	adult					227:231	the filterfeeding adult	209:231	the filterfeeding adult	209:231	Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult.
30471266	0	100	dep	revisited	9:17	arg1	and					19:21	and	19:21	and	19:21	Papillae revisited and the nature of the adhesive secreting collocytes.
30471266	10	101	theme	small	1344:1348	arg1	vesicles					1360:1367	small endocytic vesicles	1344:1367	small endocytic vesicles	1344:1367	CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins.
30304332	0	0	theme	colonic	74:80	arg1	microbiota					82:91	the human colonic microbiota	64:91	the human colonic microbiota	64:91	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota.
30304332	6	1	theme	LEfSe	1235:1239	arg1	ovatus					1227:1232	Bacteroides ovatus	1215:1232	Bacteroides ovatus	1215:1232	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	6	1	theme	LEfSe	1235:1239	arg1	P					1241:1241	LEfSe P	1235:1241	LEfSe P = 0.001	1235:1249	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	7	2	theme	simple	1424:1429	arg1	homopolymers					1431:1442	simple homopolymers	1424:1442	simple homopolymers	1424:1442	The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides promoted greater diversity than simple homopolymers, such as inulin.
30304332	7	2	theme	simple	1424:1429	arg1	inulin					1453:1458	inulin	1453:1458	inulin	1453:1458	The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides promoted greater diversity than simple homopolymers, such as inulin.
30304332	2	3	theme	growth	345:350	arg1	substrates					352:361	growth substrates	345:361	growth substrates	345:361	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	1	4	theme	diversity	233:241	arg1	determinant					218:228	one possible determinant	205:228	one possible determinant of diversity	205:241	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	0	5	theme	human	68:72	arg1	microbiota					82:91	the human colonic microbiota	64:91	the human colonic microbiota	64:91	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota.
30304332	8	6	theme	health	1528:1533	arg1	benefits					1535:1542	health benefits	1528:1542	health benefits	1528:1542	These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.
30304332	0	7	from	Impact	0:5	arg1	diversity					51:59	the diversity	47:59	the diversity of the human colonic microbiota	47:91	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota.
30304332	4	8	dep	3-	896:897	arg1	the					892:894	the	892:894	the	892:894	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	2	9	theme	in	284:285	arg1	conditions					273:282	carefully controlled conditions	252:282	carefully controlled conditions in vitro	252:291	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	0	10	theme	microbiota	82:91	arg1	diversity					51:59	the diversity	47:59	the diversity of the human colonic microbiota	47:91	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota.
30304332	3	11	dep	arabinoxylan-oligosaccharides	579:607	arg1	either					572:577	either	572:577	either	572:577	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	2	12	dep	in	284:285	arg1	vitro					287:291	vitro	287:291	vitro	287:291	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	8	13	theme	substrate	1635:1643	arg1	mixtures					1645:1652	substrate mixtures	1635:1652	substrate mixtures	1635:1652	These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.
30304332	5	14	theme	phylum	1065:1070	arg1	level					1083:1087	the phylum and family level	1061:1087	level	1083:1087	The communities enriched in these fermenters did not differ greatly at the phylum and family level, but were markedly different at the species level.
30304332	2	15	theme	microbiota	412:421	arg1	diversity					381:389	species diversity	373:389	species diversity of the human colonic microbiota	373:421	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	2	16	theme	controlled	262:271	arg1	conditions					273:282	carefully controlled conditions	252:282	carefully controlled conditions in vitro	252:291	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	1	17	attach	linked	152:157	arg2	diversity					98:106	The diversity	94:106	The diversity of the colonic microbial community	94:141	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	1	17	attach	linked	152:157	arg3	adults					174:179	adults	174:179	adults	174:179	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	3	18	theme	single	550:555	arg1	carbohydrates					557:569	single carbohydrates	550:569	single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin)	550:633	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	18	theme	single	550:555	arg1	arabinoxylan-oligosaccharides					579:607	arabinoxylan-oligosaccharides	579:607	arabinoxylan-oligosaccharides (AXOS)	579:614	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	18	theme	single	550:555	arg1	pectin					617:622	pectin	617:622	pectin	617:622	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	18	theme	single	550:555	arg1	inulin					627:632	inulin	627:632	inulin	627:632	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	6	19	dep	=	1243:1243	arg1	0.001					1245:1249	0.001	1245:1249	0.001	1245:1249	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	5	20	theme	family	1076:1081	arg1	level					1083:1087	the phylum and family level	1061:1087	level	1083:1087	The communities enriched in these fermenters did not differ greatly at the phylum and family level, but were markedly different at the species level.
30304332	4	21	theme	first	842:846	arg1	d					850:850	the first 6 d	838:850	the first 6 d	838:850	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	5	22	theme	species	1125:1131	arg1	level					1133:1137	the species level	1121:1137	the species level	1121:1137	The communities enriched in these fermenters did not differ greatly at the phylum and family level, but were markedly different at the species level.
30304332	2	23	dep	complexity	314:323	arg1	the					310:312	the	310:312	the	310:312	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	2	24	used	used	247:250	arg2	We					244:245	We	244:245	We	244:245	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	3	25	theme	resistant	727:735	arg1	sources					782:788	energy sources	775:788	energy sources	775:788	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	25	theme	resistant	727:735	arg1	β-glucan					745:752	β-glucan	745:752	β-glucan	745:752	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	25	theme	resistant	727:735	arg1	starch					737:742	resistant starch	727:742	resistant starch	727:742	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	25	theme	resistant	727:735	arg1	galactomannan					758:770	galactomannan	758:770	galactomannan	758:770	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	5	26	from	level	1133:1137	arg1	communities					994:1004	The communities	990:1004	The communities enriched in these fermenters	990:1033	The communities enriched in these fermenters did not differ greatly at the phylum and family level, but were markedly different at the species level.
30304332	5	26	from	level	1133:1137	arg1	different					1108:1116	different	1108:1116	different	1108:1116	The communities enriched in these fermenters did not differ greatly at the phylum and family level, but were markedly different at the species level.
30304332	6	27	theme	greater	1273:1279	arg1	success					1281:1287	significantly greater success	1259:1287	significantly greater success	1259:1287	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	2	28	theme	species	373:379	arg1	diversity					381:389	species diversity	373:389	species diversity of the human colonic microbiota	373:421	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	0	29	theme	substrate	23:31	arg1	complexity					33:42	carbohydrate substrate complexity	10:42	carbohydrate substrate complexity	10:42	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota.
30304332	3	30	theme	anaerobic	458:466	arg1	fermenters					468:477	five parallel anaerobic fermenters	444:477	five parallel anaerobic fermenters that received identical faecal inocula	444:516	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	0	31	theme	carbohydrate	10:21	arg1	complexity					33:42	carbohydrate substrate complexity	10:42	carbohydrate substrate complexity	10:42	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota.
30304332	8	32	theme	dietary	1489:1495	arg1	strategies					1497:1506	dietary strategies	1489:1506	dietary strategies intended to achieve health benefits by increasing gut microbiota diversity	1489:1581	These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.
30304332	3	33	dep	carbohydrates	557:569	arg1	pectin					617:622	pectin	617:622	pectin	617:622	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	33	dep	carbohydrates	557:569	arg1	arabinoxylan-oligosaccharides					579:607	arabinoxylan-oligosaccharides	579:607	arabinoxylan-oligosaccharides (AXOS)	579:614	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	33	dep	carbohydrates	557:569	arg1	carbohydrates					557:569	single carbohydrates	550:569	single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin)	550:633	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	33	dep	carbohydrates	557:569	arg1	inulin					627:632	inulin	627:632	inulin	627:632	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	33	dep	carbohydrates	557:569	arg1	AXOS					610:613	AXOS	610:613	AXOS	610:613	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	1	34	theme	diet	185:188	arg1	composition					190:200	diet composition	185:200	diet composition	185:200	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	8	35	theme	microbiota	1562:1571	arg1	diversity					1573:1581	gut microbiota diversity	1558:1581	gut microbiota diversity	1558:1581	These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.
30304332	7	36	theme	complex	1319:1325	arg1	pectin					1351:1356	pectin	1351:1356	pectin	1351:1356	The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides promoted greater diversity than simple homopolymers, such as inulin.
30304332	7	36	theme	complex	1319:1325	arg1	arabinoxylan-oligosaccharides					1362:1390	arabinoxylan-oligosaccharides	1362:1390	arabinoxylan-oligosaccharides	1362:1390	The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides promoted greater diversity than simple homopolymers, such as inulin.
30304332	7	36	theme	complex	1319:1325	arg1	polysaccharides					1327:1341	The complex polysaccharides	1315:1341	The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides	1315:1390	The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides promoted greater diversity than simple homopolymers, such as inulin.
30304332	2	37	theme	colonic	404:410	arg1	microbiota					412:421	the human colonic microbiota	394:421	the human colonic microbiota	394:421	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	0	38	theme	complexity	33:42	arg1	Impact					0:5	Impact	0:5	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota	0:91	Impact of carbohydrate substrate complexity on the diversity of the human colonic microbiota.
30304332	8	39	theme	gut	1558:1560	arg1	diversity					1573:1581	gut microbiota diversity	1558:1581	gut microbiota diversity	1558:1581	These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.
30304332	2	40	theme	human	398:402	arg1	microbiota					412:421	the human colonic microbiota	394:421	the human colonic microbiota	394:421	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	3	41	contain	contained	717:725	arg2	galactomannan					758:770	galactomannan	758:770	galactomannan	758:770	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	41	contain	contained	717:725	arg1	6-mix					692:696	6-mix	692:696	6-mix	692:696	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	41	contain	contained	717:725	arg2	β-glucan					745:752	β-glucan	745:752	β-glucan	745:752	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	41	contain	contained	717:725	arg2	starch					737:742	resistant starch	727:742	resistant starch	727:742	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	41	contain	contained	717:725	arg2	sources					782:788	energy sources	775:788	energy sources	775:788	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	6	42	dep	others	1199:1204	arg1	such					1207:1210	such	1207:1210	such	1207:1210	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	4	43	theme	microbial	813:821	arg1	diversity					823:831	less microbial diversity	808:831	less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes	808:909	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	3	44	theme	identical	493:501	arg1	inocula					510:516	identical faecal inocula	493:516	identical faecal inocula	493:516	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	4	45	theme	microbiota	968:977	arg1	diversity					979:987	microbiota diversity	968:987	microbiota diversity	968:987	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	4	46	theme	other	861:865	arg1	substrates					878:887	the other two single substrates or the 3- and 6-mixes	857:909	the other two single substrates or the 3- and 6-mixes	857:909	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	6	47	theme	single	1173:1178	arg1	substrates					1180:1189	single substrates	1173:1189	single substrates	1173:1189	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	3	48	theme	faecal	503:508	arg1	inocula					510:516	identical faecal inocula	493:516	identical faecal inocula	493:516	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	7	49	theme	greater	1401:1407	arg1	diversity					1409:1417	greater diversity	1401:1417	greater diversity	1401:1417	The complex polysaccharides such as pectin and arabinoxylan-oligosaccharides promoted greater diversity than simple homopolymers, such as inulin.
30304332	6	50	theme	=	1243:1243	arg1	ovatus					1227:1232	Bacteroides ovatus	1215:1232	Bacteroides ovatus	1215:1232	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	6	50	theme	=	1243:1243	arg1	P					1241:1241	LEfSe P	1235:1241	LEfSe P = 0.001	1235:1249	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	3	51	theme	carbohydrates	666:678	arg1	3-mix					646:650	a '3-mix'	643:651	a '3-mix' of all three carbohydrates	643:678	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	1	52	theme	colonic	115:121	arg1	community					133:141	the colonic microbial community	111:141	the colonic microbial community	111:141	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	4	53	theme	single	871:876	arg1	substrates					878:887	the other two single substrates or the 3- and 6-mixes	857:909	the other two single substrates or the 3- and 6-mixes	857:909	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	6	54	theme	Certain	1140:1146	arg1	species					1148:1154	Certain species	1140:1154	Certain species	1140:1154	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	1	55	theme	microbial	123:131	arg1	community					133:141	the colonic microbial community	111:141	the colonic microbial community	111:141	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	6	56	theme	mixed	1298:1302	arg1	substrate					1304:1312	the mixed substrate	1294:1312	the mixed substrate	1294:1312	Certain species were promoted by single substrates, whilst others (such as Bacteroides ovatus, LEfSe P = 0.001) showed significantly greater success with the mixed substrate.
30304332	1	57	theme	possible	209:216	arg1	determinant					218:228	one possible determinant	205:228	one possible determinant of diversity	205:241	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	4	58	dep	substrates	878:887	arg1	6-mixes					903:909	6-mixes	903:909	6-mixes	903:909	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	4	58	dep	substrates	878:887	arg1	3-					896:897	3-	896:897	3-	896:897	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	3	59	theme	parallel	449:456	arg1	fermenters					468:477	five parallel anaerobic fermenters	444:477	five parallel anaerobic fermenters that received identical faecal inocula	444:516	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	1	60	theme	community	133:141	arg1	diversity					98:106	The diversity	94:106	The diversity of the colonic microbial community	94:141	The diversity of the colonic microbial community has been linked with health in adults and diet composition is one possible determinant of diversity.
30304332	8	61	theme	non-digestible	1605:1618	arg1	substrates					1620:1629	complex non-digestible substrates	1597:1629	complex non-digestible substrates	1597:1629	These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.
30304332	4	62	theme	substrate	925:933	arg1	complexity					935:944	substrate complexity	925:944	substrate complexity	925:944	Inulin supported less microbial diversity over the first 6 d than the other two single substrates or the 3- and 6-mixes, showing that substrate complexity is key to influencing microbiota diversity.
30304332	8	63	theme	complex	1597:1603	arg1	substrates					1620:1629	complex non-digestible substrates	1597:1629	complex non-digestible substrates	1597:1629	These findings suggest that dietary strategies intended to achieve health benefits by increasing gut microbiota diversity should employ complex non-digestible substrates and substrate mixtures.
30304332	2	64	theme	substrates	352:361	arg1	multiplicity					329:340	multiplicity	329:340	multiplicity	329:340	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	2	64	theme	substrates	352:361	arg1	complexity					314:323	complexity	314:323	complexity	314:323	We used carefully controlled conditions in vitro to determine how the complexity and multiplicity of growth substrates influence species diversity of the human colonic microbiota.
30304332	3	65	theme	energy	775:780	arg1	sources					782:788	energy sources	775:788	energy sources	775:788	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	65	theme	energy	775:780	arg1	β-glucan					745:752	β-glucan	745:752	β-glucan	745:752	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	65	theme	energy	775:780	arg1	starch					737:742	resistant starch	727:742	resistant starch	727:742	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
30304332	3	65	theme	energy	775:780	arg1	galactomannan					758:770	galactomannan	758:770	galactomannan	758:770	In each experiment, five parallel anaerobic fermenters that received identical faecal inocula were supplied continuously with single carbohydrates (either arabinoxylan-oligosaccharides (AXOS), pectin or inulin) or with a '3-mix' of all three carbohydrates, or with a '6-mix' that additionally contained resistant starch, β-glucan and galactomannan as energy sources.
29266248	2	0	theme	cell	559:562	arg1	density					569:575	cell wall density	559:575	cell wall density of individual cells	559:595	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	0	1	theme	cell	130:133	arg1	biosynthesis					140:151	secondary cell wall biosynthesis	120:151	secondary cell wall biosynthesis	120:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	1	2	theme	secondary	384:392	arg1	formation					404:412	secondary cell wall formation	384:412	secondary cell wall formation	384:412	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	3	theme	wall	399:402	arg1	formation					404:412	secondary cell wall formation	384:412	secondary cell wall formation	384:412	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	5	4	theme	biosynthetic	1139:1150	arg1	genes					1152:1156	lignin biosynthetic genes	1132:1156	lignin biosynthetic genes	1132:1156	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	2	5	theme	individual	580:589	arg1	cells					591:595	individual cells	580:595	individual cells	580:595	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	4	6	theme	interunit	965:973	arg1	linkages					975:982	lignin interunit linkages	958:982	lignin interunit linkages	958:982	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	6	7	theme	present	1183:1189	arg1	data					1191:1194	Our present data	1179:1194	Our present data	1179:1194	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	6	8	theme	chimeric	1236:1243	arg1	factor					1259:1264	the chimeric transcription factor	1232:1264	the chimeric transcription factor	1232:1264	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	0	9	theme	rice	95:98	arg1	regulator					107:115	the rice master regulator	91:115	the rice master regulator of secondary cell wall biosynthesis	91:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	3	10	theme	lignin	719:724	arg1	expressions					744:754	lignin biosynthetic gene expressions	719:754	lignin biosynthetic gene expressions	719:754	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	6	11	theme	factor	1259:1264	arg1	overexpression					1214:1227	the overexpression	1210:1227	the overexpression of the chimeric transcription factor	1210:1264	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	2	12	theme	cell	535:538	arg1	thickness					545:553	an increased cell wall thickness	522:553	an increased cell wall thickness	522:553	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	3	13	theme	polysaccharide	700:713	arg1	induction					687:695	the induction	683:695	the induction of polysaccharide and lignin biosynthetic gene expressions	683:754	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	0	14	theme	secondary	120:128	arg1	biosynthesis					140:151	secondary cell wall biosynthesis	120:151	secondary cell wall biosynthesis	120:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	1	15	theme	master	363:368	arg1	regulator					370:378	a transcription factor 'master regulator'	339:379	a transcription factor 'master regulator' of secondary cell wall formation in rice	339:420	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	15	theme	master	363:368	arg1	sativa					322:327	Oryza sativa	316:327	Oryza sativa (OsSWN1)	316:336	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	0	16	theme	wall	135:138	arg1	biosynthesis					140:151	secondary cell wall biosynthesis	120:151	secondary cell wall biosynthesis	120:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	3	17	theme	significant	782:792	arg1	impact					794:799	no significant impact	779:799	no significant impact on the lignin content in the transgenic plants	779:846	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	1	18	from	Arabidopsis	487:497	arg1	control					429:435	control	429:435	control of the fiber preferential NST3/SND1 promoter from Arabidopsis	429:497	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	18	from	Arabidopsis	487:497	arg1	promoter					473:480	the fiber preferential NST3/SND1 promoter	440:480	the fiber preferential NST3/SND1 promoter from Arabidopsis	440:497	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	3	19	theme	gene	739:742	arg1	expressions					744:754	lignin biosynthetic gene expressions	719:754	lignin biosynthetic gene expressions	719:754	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	0	20	theme	lignin	39:44	arg1	content					46:52	lignin content	39:52	lignin content	39:52	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	1	21	theme	NAM/ATAF/CUC	275:286	arg1	protein					301:307	secondary wall NAM/ATAF/CUC (NAC) domain protein 1	260:309	secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice,	260:421	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	2	22	theme	wood	653:656	arg1	density					658:664	an increased wood density	640:664	stems as well as an increased wood density	623:664	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	1	23	from	regulator	370:378	arg1	rice					417:420	rice	417:420	rice	417:420	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	24	theme	Oryza	316:320	arg1	regulator					370:378	a transcription factor 'master regulator'	339:379	a transcription factor 'master regulator' of secondary cell wall formation in rice	339:420	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	24	theme	Oryza	316:320	arg1	sativa					322:327	Oryza sativa	316:327	Oryza sativa (OsSWN1)	316:336	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	24	theme	Oryza	316:320	arg1	OsSWN1					330:335	OsSWN1	330:335	OsSWN1	330:335	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	3	25	theme	lignin	808:813	arg1	content					815:821	the lignin content	804:821	the lignin content in the transgenic plants	804:846	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	4	26	theme	chemical	874:881	arg1	analyses					883:890	wet and dry chemical analyses	862:890	wet and dry chemical analyses of lignin	862:900	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	0	27	from	Change	0:5	arg1	poplar					69:74	transgenic poplar	58:74	transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis	58:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	0	27	from	Change	0:5	arg1	structure					17:25	lignin structure	10:25	lignin structure	10:25	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	0	27	from	Change	0:5	arg1	content					46:52	lignin content	39:52	lignin content	39:52	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	0	28	theme	transgenic	58:67	arg1	poplar					69:74	transgenic poplar	58:74	transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis	58:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	2	29	theme	cells	591:595	arg1	density					569:575	cell wall density	559:575	cell wall density of individual cells	559:595	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	2	29	theme	cells	591:595	arg1	thickness					545:553	an increased cell wall thickness	522:553	an increased cell wall thickness	522:553	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	5	30	theme	expression	1027:1036	arg1	analysis					1038:1045	gene expression analysis	1022:1045	gene expression analysis	1022:1045	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	3	31	theme	transgenic	830:839	arg1	plants					841:846	the transgenic plants	826:846	the transgenic plants	826:846	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	2	32	theme	stems	623:627	arg1	xylem					614:618	the secondary xylem	600:618	the secondary xylem of stems as well as an increased wood density	600:664	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	5	33	from	analysis	1038:1045	arg1	results					1009:1015	The results	1005:1015	The results from gene expression analysis	1005:1045	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	1	34	theme	secondary	260:268	arg1	NAM/ATAF/CUC					275:286	secondary wall NAM/ATAF/CUC	260:286	secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice,	260:421	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	34	theme	secondary	260:268	arg1	NAC					289:291	NAC	289:291	NAC	289:291	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	4	35	theme	lignin	958:963	arg1	linkages					975:982	lignin interunit linkages	958:982	lignin interunit linkages	958:982	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	0	36	theme	lignin	10:15	arg1	structure					17:25	lignin structure	10:25	lignin structure	10:25	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	4	37	from	composition	943:953	arg1	lines					998:1002	transgenic lines	987:1002	transgenic lines	987:1002	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	1	38	from	sativa	322:327	arg1	protein					301:307	secondary wall NAM/ATAF/CUC (NAC) domain protein 1	260:309	secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice,	260:421	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	39	theme	domain	294:299	arg1	protein					301:307	secondary wall NAM/ATAF/CUC (NAC) domain protein 1	260:309	secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice,	260:421	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	40	theme	fiber	444:448	arg1	promoter					473:480	the fiber preferential NST3/SND1 promoter	440:480	the fiber preferential NST3/SND1 promoter from Arabidopsis	440:497	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	5	41	theme	genes	1152:1156	arg1	induction					1119:1127	an unbalanced induction	1105:1127	an unbalanced induction of lignin biosynthetic genes in transgenic lines	1105:1176	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	1	42	theme	NST3/SND1	463:471	arg1	promoter					473:480	the fiber preferential NST3/SND1 promoter	440:480	the fiber preferential NST3/SND1 promoter from Arabidopsis	440:497	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	5	43	theme	transgenic	1161:1170	arg1	lines					1172:1176	transgenic lines	1161:1176	transgenic lines	1161:1176	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	3	44	theme	expressions	744:754	arg1	induction					687:695	the induction	683:695	the induction of polysaccharide and lignin biosynthetic gene expressions	683:754	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	4	45	theme	linkages	975:982	arg1	composition					943:953	the composition	939:953	the composition of lignin interunit linkages in transgenic lines	939:1002	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	1	46	theme	poplar	228:233	arg1	plants					235:240	transgenic poplar plants	217:240	transgenic poplar plants	217:240	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	4	47	theme	transgenic	987:996	arg1	lines					998:1002	transgenic lines	987:1002	transgenic lines	987:1002	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	5	48	from	changes	1075:1081	arg1	lignin					1086:1091	lignin	1086:1091	lignin	1086:1091	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	1	49	theme	cell	394:397	arg1	formation					404:412	secondary cell wall formation	384:412	secondary cell wall formation	384:412	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	5	50	theme	lignin	1132:1137	arg1	genes					1152:1156	lignin biosynthetic genes	1132:1156	lignin biosynthetic genes	1132:1156	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	2	51	theme	wall	540:543	arg1	thickness					545:553	an increased cell wall thickness	522:553	an increased cell wall thickness	522:553	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	3	52	from	content	815:821	arg1	plants					841:846	the transgenic plants	826:846	the transgenic plants	826:846	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	1	53	theme	formation	404:412	arg1	regulator					370:378	a transcription factor 'master regulator'	339:379	a transcription factor 'master regulator' of secondary cell wall formation in rice	339:420	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	53	theme	formation	404:412	arg1	sativa					322:327	Oryza sativa	316:327	Oryza sativa (OsSWN1)	316:336	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	6	54	theme	components	1319:1328	arg1	deposition					1285:1294	accelerated deposition	1273:1294	accelerated deposition of secondary cell wall components including lignin and polysaccharides	1273:1365	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	2	55	theme	wall	564:567	arg1	density					569:575	cell wall density	559:575	cell wall density of individual cells	559:595	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	3	56	from	impact	794:799	arg1	content					815:821	the lignin content	804:821	the lignin content in the transgenic plants	804:846	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	0	57	theme	master	100:105	arg1	regulator					107:115	the rice master regulator	91:115	the rice master regulator of secondary cell wall biosynthesis	91:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	2	58	theme	Transgenic	500:509	arg1	plants					511:516	Transgenic plants	500:516	Transgenic plants	500:516	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	5	59	from	induction	1119:1127	arg1	lines					1172:1176	transgenic lines	1161:1176	transgenic lines	1161:1176	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	1	60	theme	transcription	341:353	arg1	regulator					370:378	a transcription factor 'master regulator'	339:379	a transcription factor 'master regulator' of secondary cell wall formation in rice	339:420	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	60	theme	transcription	341:353	arg1	sativa					322:327	Oryza sativa	316:327	Oryza sativa (OsSWN1)	316:336	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	61	theme	wood	191:194	arg1	formation					196:204	wood formation	191:204	wood formation of wood in transgenic poplar plants	191:240	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	4	62	theme	wet	862:864	arg1	analyses					883:890	wet and dry chemical analyses	862:890	wet and dry chemical analyses of lignin	862:900	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	2	63	theme	increased	643:651	arg1	density					658:664	an increased wood density	640:664	stems as well as an increased wood density	623:664	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	3	64	theme	biosynthetic	726:737	arg1	expressions					744:754	lignin biosynthetic gene expressions	719:754	lignin biosynthetic gene expressions	719:754	OsSWN1 triggers the induction of polysaccharide and lignin biosynthetic gene expressions, however, resulting in no significant impact on the lignin content in the transgenic plants.
29266248	6	65	theme	transcription	1245:1257	arg1	factor					1259:1264	the chimeric transcription factor	1232:1264	the chimeric transcription factor	1232:1264	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	1	66	from	formation	196:204	arg1	plants					235:240	transgenic poplar plants	217:240	transgenic poplar plants	217:240	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	2	67	theme	increased	525:533	arg1	thickness					545:553	an increased cell wall thickness	522:553	an increased cell wall thickness	522:553	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	0	68	theme	biosynthesis	140:151	arg1	regulator					107:115	the rice master regulator	91:115	the rice master regulator of secondary cell wall biosynthesis	91:151	Change in lignin structure, but not in lignin content, in transgenic poplar overexpressing the rice master regulator of secondary cell wall biosynthesis.
29266248	4	69	theme	lignin	895:900	arg1	analyses					883:890	wet and dry chemical analyses	862:890	wet and dry chemical analyses of lignin	862:900	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	2	70	theme	density	658:664	arg1	xylem					614:618	the secondary xylem	600:618	the secondary xylem of stems as well as an increased wood density	600:664	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	6	71	theme	cell	1309:1312	arg1	components					1319:1328	secondary cell wall components	1299:1328	secondary cell wall components	1299:1328	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	6	72	theme	accelerated	1273:1283	arg1	deposition					1285:1294	accelerated deposition	1273:1294	accelerated deposition of secondary cell wall components including lignin and polysaccharides	1273:1365	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	2	73	theme	secondary	604:612	arg1	xylem					614:618	the secondary xylem	600:618	the secondary xylem of stems as well as an increased wood density	600:664	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	6	74	theme	wall	1314:1317	arg1	components					1319:1328	secondary cell wall components	1299:1328	secondary cell wall components	1299:1328	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	5	75	theme	structural	1064:1073	arg1	changes					1075:1081	the structural changes	1060:1081	the structural changes in lignin	1060:1091	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	5	75	theme	structural	1064:1073	arg1	due					1098:1100	due	1098:1100	due	1098:1100	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	4	76	theme	dry	870:872	arg1	analyses					883:890	wet and dry chemical analyses	862:890	wet and dry chemical analyses of lignin	862:900	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	6	77	theme	secondary	1299:1307	arg1	components					1319:1328	secondary cell wall components	1299:1328	secondary cell wall components	1299:1328	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	5	78	theme	gene	1022:1025	arg1	analysis					1038:1045	gene expression analysis	1022:1045	gene expression analysis	1022:1045	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	1	79	theme	wood	209:212	arg1	formation					196:204	wood formation	191:204	wood formation of wood in transgenic poplar plants	191:240	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	2	80	contain	had	518:520	arg2	density					569:575	cell wall density	559:575	cell wall density of individual cells	559:595	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	2	80	contain	had	518:520	arg1	plants					511:516	Transgenic plants	500:516	Transgenic plants	500:516	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	2	80	contain	had	518:520	arg2	thickness					545:553	an increased cell wall thickness	522:553	an increased cell wall thickness	522:553	Transgenic plants had an increased cell wall thickness and cell wall density of individual cells in the secondary xylem of stems as well as an increased wood density.
29266248	1	81	theme	wall	270:273	arg1	NAM/ATAF/CUC					275:286	secondary wall NAM/ATAF/CUC	260:286	secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice,	260:421	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	81	theme	wall	270:273	arg1	NAC					289:291	NAC	289:291	NAC	289:291	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	6	82	theme	acquired	1378:1385	arg1	mechanism					1387:1395	an acquired mechanism	1375:1395	an acquired mechanism	1375:1395	Our present data indicate that the overexpression of the chimeric transcription factor causes accelerated deposition of secondary cell wall components including lignin and polysaccharides through an acquired mechanism.
29266248	5	83	theme	unbalanced	1108:1117	arg1	induction					1119:1127	an unbalanced induction	1105:1127	an unbalanced induction of lignin biosynthetic genes in transgenic lines	1105:1176	The results from gene expression analysis suggest that the structural changes in lignin were due to an unbalanced induction of lignin biosynthetic genes in transgenic lines.
29266248	1	84	from	control	429:435	arg1	Arabidopsis					487:497	Arabidopsis	487:497	Arabidopsis	487:497	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	4	85	theme	S/G	922:924	arg1	ratio					926:930	S/G ratio	922:930	S/G ratio	922:930	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	1	86	theme	preferential	450:461	arg1	promoter					473:480	the fiber preferential NST3/SND1 promoter	440:480	the fiber preferential NST3/SND1 promoter from Arabidopsis	440:497	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	4	87	from	changes	911:917	arg1	composition					943:953	the composition	939:953	the composition of lignin interunit linkages in transgenic lines	939:1002	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	4	87	from	changes	911:917	arg1	ratio					926:930	S/G ratio	922:930	S/G ratio	922:930	In contrast, wet and dry chemical analyses of lignin revealed changes in S/G ratio and in the composition of lignin interunit linkages in transgenic lines.
29266248	1	88	theme	promoter	473:480	arg1	control					429:435	control	429:435	control of the fiber preferential NST3/SND1 promoter from Arabidopsis	429:497	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
29266248	1	89	theme	transgenic	217:226	arg1	plants					235:240	transgenic poplar plants	217:240	transgenic poplar plants	217:240	We previously succeeded in enhancing wood formation of wood in transgenic poplar plants by overexpressing secondary wall NAM/ATAF/CUC (NAC) domain protein 1 from Oryza sativa (OsSWN1), a transcription factor 'master regulator' of secondary cell wall formation in rice, under control of the fiber preferential NST3/SND1 promoter from Arabidopsis.
30116297	9	0	theme	substrate	2014:2022	arg1	degradation					1997:2007	efficient degradation	1987:2007	efficient degradation	1987:2007	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	9	0	theme	substrate	2014:2022	arg1	adaptation					1972:1981	quick adaptation	1966:1981	quick adaptation	1966:1981	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	8	1	theme	enzyme	1750:1755	arg1	cocktail					1757:1764	a commercially available fungal enzyme cocktail	1718:1764	a commercially available fungal enzyme cocktail	1718:1764	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	3	2	theme	sugars	779:784	arg1	production					753:762	the production	749:762	the production of fermentable sugars from cellulosic biomass	749:808	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	2	3	theme	plant-derived	358:370	arg1	polysaccharides					372:386	plant-derived polysaccharides	358:386	plant-derived polysaccharides	358:386	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	6	4	theme	single	1330:1335	arg1	components					1337:1346	seven single components	1324:1346	seven single components (including the scaffoldin protein and a β-glucosidase)	1324:1401	Based on these results, we predicted a synthetic cellulosome complex consisting of seven single components (including the scaffoldin protein and a β-glucosidase) and characterized it biochemically.
30116297	6	5	theme	synthetic	1280:1288	arg1	complex					1302:1308	a synthetic cellulosome complex	1278:1308	a synthetic cellulosome complex consisting of seven single components (including the scaffoldin protein and a β-glucosidase)	1278:1401	Based on these results, we predicted a synthetic cellulosome complex consisting of seven single components (including the scaffoldin protein and a β-glucosidase) and characterized it biochemically.
30116297	9	6	theme	interest	2027:2034	arg1	substrate					2014:2022	a substrate	2012:2022	a substrate of interest	2012:2034	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	1	7	theme	valorizing	282:291	arg1	biomass					293:299	cost-effectively valorizing biomass	265:299	cost-effectively valorizing biomass in a new bio-economy	265:320	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	7	8	theme	native	1574:1579	arg1	cellulosome					1581:1591	the native cellulosome	1570:1591	the native cellulosome	1570:1591	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	6	9	theme	scaffoldin	1363:1372	arg1	protein					1374:1380	the scaffoldin protein	1359:1380	the scaffoldin protein	1359:1380	Based on these results, we predicted a synthetic cellulosome complex consisting of seven single components (including the scaffoldin protein and a β-glucosidase) and characterized it biochemically.
30116297	7	10	theme	optimal	1526:1532	arg1	pH					1534:1535	an optimal pH	1523:1535	an optimal pH	1523:1535	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	3	11	theme	cellulolytic	636:647	arg1	thermocellum					671:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	4	12	from	wood	1044:1047	arg1	pulp					1029:1032	Kraft pulp	1023:1032	Kraft pulp from pine wood as the substrate	1023:1064	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	3	13	theme	thermostable	556:567	arg1	complex					592:598	a thermostable multi-enzyme cellulase complex	554:598	a thermostable multi-enzyme cellulase complex	554:598	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	13	theme	thermostable	556:567	arg1	cellulosome					605:615	the cellulosome	601:615	the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum	601:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	13	theme	thermostable	556:567	arg1	promising					687:695	promising	687:695	promising	687:695	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	9	14	theme	synthetic	1832:1840	arg1	complexes					1865:1873	synthetic bacterial multi-enzyme complexes	1832:1873	synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum	1832:1917	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	9	14	theme	synthetic	1832:1840	arg1	platform					1949:1956	a versatile platform	1937:1956	a versatile platform for the quick adaptation and efficient degradation of a substrate of interest	1937:2034	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	9	15	theme	multi-enzyme	1852:1863	arg1	complexes					1865:1873	synthetic bacterial multi-enzyme complexes	1832:1873	synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum	1832:1917	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	9	15	theme	multi-enzyme	1852:1863	arg1	platform					1949:1956	a versatile platform	1937:1956	a versatile platform for the quick adaptation and efficient degradation of a substrate of interest	1937:2034	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	0	16	theme	enzymatic	121:129	arg1	functions					136:144	the enzymatic core functions	117:144	the enzymatic core functions	117:144	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	9	17	theme	versatile	1939:1947	arg1	complexes					1865:1873	synthetic bacterial multi-enzyme complexes	1832:1873	synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum	1832:1917	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	9	17	theme	versatile	1939:1947	arg1	platform					1949:1956	a versatile platform	1937:1956	a versatile platform for the quick adaptation and efficient degradation of a substrate of interest	1937:2034	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	1	18	theme	cellulase	228:236	arg1	blends					238:243	efficient cellulase blends	218:243	efficient cellulase blends	218:243	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	4	19	theme	enzymes	1012:1018	arg1	relationship					982:993	the function-activity relationship	960:993	the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate	960:1064	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	7	20	theme	optimal	1486:1492	arg1	activity					1494:1501	optimal activity	1486:1501	optimal activity	1486:1501	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	3	21	from	biomass	802:808	arg1	production					753:762	the production	749:762	the production of fermentable sugars from cellulosic biomass	749:808	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	21	from	biomass	802:808	arg1	sugars					779:784	fermentable sugars	767:784	fermentable sugars from cellulosic biomass	767:808	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	0	22	theme	functions	136:144	arg1	characterization					170:185	biochemical complex characterization	150:185	biochemical complex characterization	150:185	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	0	22	theme	functions	136:144	arg1	identification					99:112	identification	99:112	identification of the enzymatic core functions	99:144	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	5	23	theme	additional	1141:1150	arg1	classes					1163:1169	additional functional classes	1141:1169	additional functional classes such as mannanase and xylanase for optimal activity on the substrate	1141:1238	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	5	23	theme	additional	1141:1150	arg1	mannanase					1179:1187	mannanase	1179:1187	mannanase	1179:1187	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	5	23	theme	additional	1141:1150	arg1	xylanase					1193:1200	xylanase	1193:1200	xylanase	1193:1200	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	3	24	theme	Clostridium	659:669	arg1	thermocellum					671:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	4	25	theme	Kraft	1023:1027	arg1	pulp					1029:1032	Kraft pulp	1023:1032	Kraft pulp from pine wood as the substrate	1023:1064	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	0	26	theme	biochemical	150:160	arg1	characterization					170:185	biochemical complex characterization	150:185	biochemical complex characterization	150:185	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	4	27	from	relationship	982:993	arg1	pulp					1029:1032	Kraft pulp	1023:1032	Kraft pulp from pine wood as the substrate	1023:1064	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	9	28	theme	thermocellum	1906:1917	arg1	cellulosome					1888:1898	the cellulosome	1884:1898	the cellulosome of C. thermocellum	1884:1917	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	0	29	theme	softwood	84:91	arg1	pulp					93:96	softwood pulp	84:96	softwood pulp	84:96	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	2	30	from	bacteria	506:513	arg1	systems					493:499	potentially equally effective cellulose-degrading systems	443:499	potentially equally effective cellulose-degrading systems from bacteria	443:513	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	5	31	theme	basic	1083:1087	arg1	complex					1107:1113	a basic exo/endoglucanase complex	1081:1113	a basic exo/endoglucanase complex	1081:1113	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	8	32	theme	synthetic	1623:1631	arg1	complex					1633:1639	a fully synthetic complex	1615:1639	a fully synthetic complex containing 47 single cellulosomal components	1615:1684	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	2	33	theme	cellulose-degrading	473:491	arg1	systems					493:499	potentially equally effective cellulose-degrading systems	443:499	potentially equally effective cellulose-degrading systems from bacteria	443:513	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	4	34	theme	cellulosomal	837:848	arg1	components					850:859	60 cellulosomal components	834:859	60 cellulosomal components	834:859	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	8	35	theme	single	1655:1660	arg1	components					1675:1684	47 single cellulosomal components	1652:1684	47 single cellulosomal components	1652:1684	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	1	36	dep	BACKGROUND	188:197	arg1	development					203:213	The development	199:213	The development of efficient cellulase blends	199:243	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	1	36	dep	BACKGROUND	188:197	arg1	factor					254:259	a key factor	248:259	a key factor for cost-effectively valorizing biomass in a new bio-economy	248:320	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	7	37	with	agreement	1540:1548	arg1	optimum					1559:1565	the optimum	1555:1565	the optimum of the native cellulosome (pH 5.8)	1555:1600	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	7	37	with	agreement	1540:1548	arg1	pH					1594:1595	pH 5.8	1594:1599	pH 5.8	1594:1599	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	9	38	theme	quick	1966:1970	arg1	adaptation					1972:1981	quick adaptation	1966:1981	quick adaptation	1966:1981	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	3	39	theme	cellulolytic	717:728	arg1	nano-machinery					730:743	cellulolytic nano-machinery	717:743	cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass	717:808	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	4	40	theme	synthetic	931:939	arg1	complexes					941:949	synthetic complexes	931:949	synthetic complexes	931:949	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	0	41	theme	cellulosome	42:52	arg1	complex					54:60	a synthetic cellulosome complex	30:60	a synthetic cellulosome complex	30:60	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	9	42	dep	adaptation	1972:1981	arg1	the					1962:1964	the	1962:1964	the	1962:1964	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	6	43	theme	cellulosome	1290:1300	arg1	complex					1302:1308	a synthetic cellulosome complex	1278:1308	a synthetic cellulosome complex consisting of seven single components (including the scaffoldin protein and a β-glucosidase)	1278:1401	Based on these results, we predicted a synthetic cellulosome complex consisting of seven single components (including the scaffoldin protein and a β-glucosidase) and characterized it biochemically.
30116297	3	44	theme	fermentable	767:777	arg1	sugars					779:784	fermentable sugars	767:784	fermentable sugars from cellulosic biomass	767:808	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	2	45	theme	enzymatic	334:342	arg1	hydrolysis					344:353	the enzymatic hydrolysis	330:353	the enzymatic hydrolysis of plant-derived polysaccharides	330:386	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	1	46	theme	blends	238:243	arg1	factor					254:259	a key factor	248:259	a key factor for cost-effectively valorizing biomass in a new bio-economy	248:320	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	1	46	theme	blends	238:243	arg1	development					203:213	The development	199:213	The development of efficient cellulase blends	199:243	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	3	47	theme	multi-enzyme	569:580	arg1	complex					592:598	a thermostable multi-enzyme cellulase complex	554:598	a thermostable multi-enzyme cellulase complex	554:598	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	47	theme	multi-enzyme	569:580	arg1	cellulosome					605:615	the cellulosome	601:615	the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum	601:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	47	theme	multi-enzyme	569:580	arg1	promising					687:695	promising	687:695	promising	687:695	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	8	48	theme	pulp	1782:1785	arg1	substrate					1787:1795	the softwood pulp substrate	1769:1795	the softwood pulp substrate	1769:1795	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	0	49	dep	Optimizing	0:9	arg1	characterization					170:185	biochemical complex characterization	150:185	biochemical complex characterization	150:185	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	0	49	dep	Optimizing	0:9	arg1	identification					99:112	identification	99:112	identification of the enzymatic core functions	99:144	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	2	50	theme	polysaccharides	372:386	arg1	hydrolysis					344:353	the enzymatic hydrolysis	330:353	the enzymatic hydrolysis of plant-derived polysaccharides	330:386	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	7	51	theme	cellulosome	1581:1591	arg1	optimum					1559:1565	the optimum	1555:1565	the optimum of the native cellulosome (pH 5.8)	1555:1600	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	7	51	theme	cellulosome	1581:1591	arg1	pH					1594:1595	pH 5.8	1594:1599	pH 5.8	1594:1599	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	4	52	theme	function-activity	964:980	arg1	relationship					982:993	the function-activity relationship	960:993	the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate	960:1064	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	8	53	theme	fungal	1743:1748	arg1	cocktail					1757:1764	a commercially available fungal enzyme cocktail	1718:1764	a commercially available fungal enzyme cocktail	1718:1764	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	1	54	theme	cost-effectively	265:280	arg1	biomass					293:299	cost-effectively valorizing biomass	265:299	cost-effectively valorizing biomass in a new bio-economy	265:320	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	2	55	link	plant-derived	358:370	arg1	polysaccharides					372:386	plant-derived polysaccharides	358:386	plant-derived polysaccharides	358:386	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	9	56	dep	CONCLUSIONS	1798:1808	arg1	show					1822:1825	show	1822:1825	show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest	1822:2034	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	1	57	from	biomass	293:299	arg1	bio-economy					310:320	a new bio-economy	304:320	a new bio-economy	304:320	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	3	58	theme	anaerobic	626:634	arg1	thermocellum					671:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	0	59	theme	core	131:134	arg1	functions					136:144	the enzymatic core functions	117:144	the enzymatic core functions	117:144	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	1	60	theme	efficient	218:226	arg1	blends					238:243	efficient cellulase blends	218:243	efficient cellulase blends	218:243	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	9	61	theme	bacterial	1842:1850	arg1	complexes					1865:1873	synthetic bacterial multi-enzyme complexes	1832:1873	synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum	1832:1917	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	9	61	theme	bacterial	1842:1850	arg1	platform					1949:1956	a versatile platform	1937:1956	a versatile platform for the quick adaptation and efficient degradation of a substrate of interest	1937:2034	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	8	62	theme	comparable	1693:1702	arg1	activity					1704:1711	comparable activity	1693:1711	comparable activity	1693:1711	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	3	63	theme	bacterium	649:657	arg1	thermocellum					671:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	the anaerobic cellulolytic bacterium Clostridium thermocellum	622:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	4	64	theme	available	1002:1010	arg1	enzymes					1012:1018	all available enzymes	998:1018	all available enzymes	998:1018	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	0	65	theme	complex	162:168	arg1	characterization					170:185	biochemical complex characterization	150:185	biochemical complex characterization	150:185	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	5	66	theme	functional	1152:1161	arg1	classes					1163:1169	additional functional classes	1141:1169	additional functional classes such as mannanase and xylanase for optimal activity on the substrate	1141:1238	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	5	66	theme	functional	1152:1161	arg1	mannanase					1179:1187	mannanase	1179:1187	mannanase	1179:1187	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	5	66	theme	functional	1152:1161	arg1	xylanase					1193:1200	xylanase	1193:1200	xylanase	1193:1200	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	7	67	theme	thermostable	1460:1471	arg1	complex					1473:1479	a highly thermostable complex	1451:1479	a highly thermostable complex with optimal activity	1451:1501	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	8	68	contain	containing	1641:1650	arg2	components					1675:1684	47 single cellulosomal components	1652:1684	47 single cellulosomal components	1652:1684	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	8	68	contain	containing	1641:1650	arg1	complex					1633:1639	a fully synthetic complex	1615:1639	a fully synthetic complex containing 47 single cellulosomal components	1615:1684	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	7	69	with	complex	1473:1479	arg1	activity					1494:1501	optimal activity	1486:1501	optimal activity	1486:1501	We obtained a highly thermostable complex with optimal activity around 60-65 °C and an optimal pH in agreement with the optimum of the native cellulosome (pH 5.8).
30116297	6	70	dep	components	1337:1346	arg1	including					1349:1357	including	1349:1357	including the scaffoldin protein and a β-glucosidase	1349:1400	Based on these results, we predicted a synthetic cellulosome complex consisting of seven single components (including the scaffoldin protein and a β-glucosidase) and characterized it biochemically.
30116297	0	71	theme	pulp	93:96	arg1	hydrolysis					70:79	the hydrolysis	66:79	the hydrolysis of softwood pulp	66:96	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	5	72	theme	optimal	1206:1212	arg1	activity					1214:1221	optimal activity	1206:1221	optimal activity on the substrate	1206:1238	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	2	73	theme	fungal	416:421	arg1	cellulases					423:432	fungal cellulases	416:432	fungal cellulases	416:432	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	5	74	from	activity	1214:1221	arg1	substrate					1230:1238	the substrate	1226:1238	the substrate	1226:1238	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	4	75	dep	RESULTS	811:817	arg1	permuted					919:926	permuted	919:926	systematically permuted in synthetic complexes	904:949	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	4	75	dep	RESULTS	811:817	arg1	produced					880:887	produced	880:887	recombinantly produced in E. coli	866:898	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	2	76	theme	effective	463:471	arg1	systems					493:499	potentially equally effective cellulose-degrading systems	443:499	potentially equally effective cellulose-degrading systems from bacteria	443:513	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	8	77	theme	cellulosomal	1662:1673	arg1	components					1675:1684	47 single cellulosomal components	1652:1684	47 single cellulosomal components	1652:1684	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	3	78	from	thermocellum	671:682	arg1	complex					592:598	a thermostable multi-enzyme cellulase complex	554:598	a thermostable multi-enzyme cellulase complex	554:598	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	78	from	thermocellum	671:682	arg1	cellulosome					605:615	the cellulosome	601:615	the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum	601:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	0	79	theme	synthetic	32:40	arg1	complex					54:60	a synthetic cellulosome complex	30:60	a synthetic cellulosome complex	30:60	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	1	80	theme	new	306:308	arg1	bio-economy					310:320	a new bio-economy	304:320	a new bio-economy	304:320	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	0	81	theme	complex	54:60	arg1	composition					15:25	the composition	11:25	the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp	11:96	Optimizing the composition of a synthetic cellulosome complex for the hydrolysis of softwood pulp: identification of the enzymatic core functions and biochemical complex characterization.
30116297	4	82	theme	pine	1039:1042	arg1	wood					1044:1047	pine wood	1039:1047	pine wood as the substrate	1039:1064	RESULTS In this study, 60 cellulosomal components were recombinantly produced in E. coli and systematically permuted in synthetic complexes to study the function-activity relationship of all available enzymes on Kraft pulp from pine wood as the substrate.
30116297	8	83	theme	softwood	1773:1780	arg1	substrate					1787:1795	the softwood pulp substrate	1769:1795	the softwood pulp substrate	1769:1795	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	5	84	theme	exo/endoglucanase	1089:1105	arg1	complex					1107:1113	a basic exo/endoglucanase complex	1081:1113	a basic exo/endoglucanase complex	1081:1113	Starting from a basic exo/endoglucanase complex, we were able to identify additional functional classes such as mannanase and xylanase for optimal activity on the substrate.
30116297	9	85	theme	efficient	1987:1995	arg1	degradation					1997:2007	efficient degradation	1987:2007	efficient degradation	1987:2007	CONCLUSIONS Our results show that synthetic bacterial multi-enzyme complexes based on the cellulosome of C. thermocellum can be applied as a versatile platform for the quick adaptation and efficient degradation of a substrate of interest.
30116297	2	86	dep	accomplished	398:409	arg1	whereas					435:441	whereas	435:441	whereas	435:441	Today, the enzymatic hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal cellulases, whereas potentially equally effective cellulose-degrading systems from bacteria have not been developed.
30116297	8	87	theme	available	1733:1741	arg1	cocktail					1757:1764	a commercially available fungal enzyme cocktail	1718:1764	a commercially available fungal enzyme cocktail	1718:1764	Remarkably, a fully synthetic complex containing 47 single cellulosomal components showed comparable activity with a commercially available fungal enzyme cocktail on the softwood pulp substrate.
30116297	3	88	from	production	753:762	arg1	biomass					802:808	cellulosic biomass	791:808	cellulosic biomass	791:808	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	89	theme	cellulosic	791:800	arg1	biomass					802:808	cellulosic biomass	791:808	cellulosic biomass	791:808	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	90	theme	cellulase	582:590	arg1	complex					592:598	a thermostable multi-enzyme cellulase complex	554:598	a thermostable multi-enzyme cellulase complex	554:598	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	90	theme	cellulase	582:590	arg1	cellulosome					605:615	the cellulosome	601:615	the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum	601:682	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	3	90	theme	cellulase	582:590	arg1	promising					687:695	promising	687:695	promising	687:695	Particularly, a thermostable multi-enzyme cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium Clostridium thermocellum is promising of being applied as cellulolytic nano-machinery for the production of fermentable sugars from cellulosic biomass.
30116297	1	91	theme	key	250:252	arg1	development					203:213	The development	199:213	The development of efficient cellulase blends	199:243	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
30116297	1	91	theme	key	250:252	arg1	factor					254:259	a key factor	248:259	a key factor for cost-effectively valorizing biomass in a new bio-economy	248:320	BACKGROUND The development of efficient cellulase blends is a key factor for cost-effectively valorizing biomass in a new bio-economy.
31129958	4	0	theme	on-demand	658:666	arg1	DecoyDeveloper					639:652	DecoyDeveloper	639:652	DecoyDeveloper	639:652	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	4	0	theme	on-demand	658:666	arg1	generator					687:695	an on-demand decoy glycopeptide generator	655:695	an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences	655:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	1	1	theme	effective	137:145	arg1	tools					158:162	effective, automated tools	137:162	effective, automated tools	137:162	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	7	2	located	found	1060:1064	arg2	tool					1024:1027	This tool	1019:1027	This tool	1019:1027	This tool is freely available and can be found at http://glycopro.chem.ku.edu/J1.php .
31129958	7	2	located	found	1060:1064	arg1	http					1069:1072	http	1069:1072	http://glycopro.chem.ku.edu/J1.php	1069:1102	This tool is freely available and can be found at http://glycopro.chem.ku.edu/J1.php .
31129958	6	3	gly	glycopeptide	997:1008	arg2	glycopeptide					997:1008	glycopeptide	997:1008	glycopeptide	997:1008	We demonstrate the tool's efficiency by applying it to a set of 80 glycopeptide targets.
31129958	5	4	theme	decoys	850:855	arg1	decoys					850:855	decoys	850:855	decoys containing complete, biologically relevant glycan and peptide sequences	850:927	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	5	4	theme	decoys	850:855	arg1	sets					842:845	large sets	836:845	large sets of decoys containing complete, biologically relevant glycan and peptide sequences	836:927	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	2	5	gly	glycopeptides	277:289	arg2	glycopeptides					277:289	glycopeptides	277:289	glycopeptides to MS data	277:300	Many creative workflows and software apps have emerged recently that offer promising capabilities for assigning glycopeptides to MS data in an automated fashion.
31129958	4	6	theme	low	743:745	arg1	differences					752:762	low mass differences	743:762	low mass differences	743:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	0	7	dep	De	30:31	arg1	Novo					33:36	Novo	33:36	Novo	33:36	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.
31129958	2	8	theme	MS	294:295	arg1	data					297:300	MS data	294:300	MS data	294:300	Many creative workflows and software apps have emerged recently that offer promising capabilities for assigning glycopeptides to MS data in an automated fashion.
31129958	3	9	theme	tools	354:358	arg1	effectiveness					331:343	The effectiveness	327:343	The effectiveness of these tools	327:358	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	3	10	dep	spectral	459:466	arg1	match					468:472	match	468:472	match	468:472	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	3	11	theme	generating	514:523	arg1	number					541:546	appropriate number	529:546	appropriate number	529:546	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	5	12	theme	complete	868:875	arg1	glycan					900:905	complete, biologically relevant glycan and peptide sequences	868:927	glycan	900:905	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	7	13	dep	http	1069:1072	arg1	//glycopro.chem.ku.edu/J1.php					1074:1102	//glycopro.chem.ku.edu/J1.php	1074:1102	http://glycopro.chem.ku.edu/J1.php	1069:1102	This tool is freely available and can be found at http://glycopro.chem.ku.edu/J1.php .
31129958	5	14	dep	complete	868:875	arg1	relevant					891:898	relevant	891:898	relevant	891:898	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	1	15	theme	Glycopeptide	68:79	arg1	field					103:107	a growing field	93:107	a growing field that is struggling to adopt effective, automated tools	93:162	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	1	15	theme	Glycopeptide	68:79	arg1	struggling					117:126	struggling	117:126	struggling	117:126	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	1	15	theme	Glycopeptide	68:79	arg1	analysis					81:88	Glycopeptide analysis	68:88	Glycopeptide analysis	68:88	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	3	16	dep	number	541:546	arg1	the					525:527	the	525:527	the	525:527	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	1	17	dep	effective	137:145	arg1	automated					148:156	automated	148:156	automated	148:156	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	3	18	theme	appropriate	529:539	arg1	number					541:546	appropriate number	529:546	appropriate number	529:546	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	5	19	theme	large	836:840	arg1	decoys					850:855	decoys	850:855	decoys containing complete, biologically relevant glycan and peptide sequences	850:927	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	5	19	theme	large	836:840	arg1	sets					842:845	large sets	836:845	large sets of decoys containing complete, biologically relevant glycan and peptide sequences	836:927	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	0	20	theme	On-Demand	19:27	arg1	Generator					57:65	An On-Demand, De Novo Decoy Glycopeptide Generator	16:65	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.	0:66	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.
31129958	4	21	with	decoys	731:736	arg1	differences					752:762	low mass differences	743:762	low mass differences	743:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	4	22	theme	high	716:719	arg1	volume					721:726	a high volume	714:726	a high volume of decoys with low mass differences	714:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	5	23	theme	user	793:796	arg1	interface					798:806	a simple user interface	784:806	a simple user interface	784:806	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	5	24	theme	simple	786:791	arg1	interface					798:806	a simple user interface	784:806	a simple user interface	784:806	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	4	25	gly	glycopeptide	674:685	arg2	glycopeptide					674:685	an on-demand decoy glycopeptide generator	655:695	an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences	655:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	2	26	theme	Many	165:168	arg1	workflows					179:187	Many creative workflows	165:187	Many creative workflows	165:187	Many creative workflows and software apps have emerged recently that offer promising capabilities for assigning glycopeptides to MS data in an automated fashion.
31129958	1	27	theme	growing	95:101	arg1	field					103:107	a growing field	93:107	a growing field that is struggling to adopt effective, automated tools	93:162	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	1	27	theme	growing	95:101	arg1	struggling					117:126	struggling	117:126	struggling	117:126	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	1	27	theme	growing	95:101	arg1	analysis					81:88	Glycopeptide analysis	68:88	Glycopeptide analysis	68:88	Glycopeptide analysis is a growing field that is struggling to adopt effective, automated tools.
31129958	3	28	gly	glycopeptide	560:571	arg2	glycopeptide					560:571	glycopeptide	560:571	glycopeptide	560:571	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	3	29	theme	glycopeptide	560:571	arg1	decoys					573:578	glycopeptide decoys	560:578	glycopeptide decoys	560:578	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	6	30	theme	targets	1010:1016	arg1	set					987:989	a set	985:989	a set of 80 glycopeptide targets	985:1016	We demonstrate the tool's efficiency by applying it to a set of 80 glycopeptide targets.
31129958	6	30	theme	targets	1010:1016	arg1	targets					1010:1016	80 glycopeptide targets	994:1016	80 glycopeptide targets	994:1016	We demonstrate the tool's efficiency by applying it to a set of 80 glycopeptide targets.
31129958	5	31	contain	has	780:782	arg2	interface					798:806	a simple user interface	784:806	a simple user interface	784:806	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	5	31	contain	has	780:782	arg1	DecoyDeveloper					765:778	DecoyDeveloper	765:778	DecoyDeveloper	765:778	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	3	32	theme	decoys	573:578	arg1	type					552:555	type	552:555	type	552:555	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	3	32	theme	decoys	573:578	arg1	number					541:546	appropriate number	529:546	appropriate number	529:546	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	3	33	theme	glycopeptide	435:446	arg1	decoy					448:452	a glycopeptide decoy	433:452	a glycopeptide decoy	433:452	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	3	33	theme	glycopeptide	435:446	arg1	spectral					459:466	spectral	459:466	spectral	459:466	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	0	34	theme	Decoy	38:42	arg1	Generator					57:65	An On-Demand, De Novo Decoy Glycopeptide Generator	16:65	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.	0:66	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.
31129958	3	35	gly	glycopeptide	435:446	arg2	glycopeptide					435:446	a glycopeptide decoy	433:452	a glycopeptide decoy	433:452	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
31129958	4	36	theme	glycopeptide	674:685	arg1	DecoyDeveloper					639:652	DecoyDeveloper	639:652	DecoyDeveloper	639:652	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	4	36	theme	glycopeptide	674:685	arg1	generator					687:695	an on-demand decoy glycopeptide generator	655:695	an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences	655:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	2	37	theme	software	193:200	arg1	apps					202:205	software apps	193:205	software apps	193:205	Many creative workflows and software apps have emerged recently that offer promising capabilities for assigning glycopeptides to MS data in an automated fashion.
31129958	4	38	theme	decoy	668:672	arg1	DecoyDeveloper					639:652	DecoyDeveloper	639:652	DecoyDeveloper	639:652	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	4	38	theme	decoy	668:672	arg1	generator					687:695	an on-demand decoy glycopeptide generator	655:695	an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences	655:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	4	39	theme	mass	747:750	arg1	differences					752:762	low mass differences	743:762	low mass differences	743:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	0	40	dep	On-Demand	19:27	arg1	De					30:31	De	30:31	De	30:31	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.
31129958	5	41	theme	peptide	911:917	arg1	sequences					919:927	complete, biologically relevant glycan and peptide sequences	868:927	sequences	919:927	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	4	42	theme	decoys	731:736	arg1	volume					721:726	a high volume	714:726	a high volume of decoys with low mass differences	714:762	To address this need, we have designed DecoyDeveloper, an on-demand decoy glycopeptide generator that can produce a high volume of decoys with low mass differences.
31129958	2	43	theme	promising	240:248	arg1	capabilities					250:261	promising capabilities	240:261	promising capabilities for assigning glycopeptides to MS data in an automated fashion	240:324	Many creative workflows and software apps have emerged recently that offer promising capabilities for assigning glycopeptides to MS data in an automated fashion.
31129958	5	44	contain	containing	857:866	arg1	decoys					850:855	decoys	850:855	decoys containing complete, biologically relevant glycan and peptide sequences	850:927	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	5	44	contain	containing	857:866	arg2	glycan					900:905	complete, biologically relevant glycan and peptide sequences	868:927	glycan	900:905	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	5	44	contain	containing	857:866	arg2	sequences					919:927	complete, biologically relevant glycan and peptide sequences	868:927	sequences	919:927	DecoyDeveloper has a simple user interface and is capable of producing large sets of decoys containing complete, biologically relevant glycan and peptide sequences.
31129958	2	45	theme	automated	308:316	arg1	fashion					318:324	an automated fashion	305:324	an automated fashion	305:324	Many creative workflows and software apps have emerged recently that offer promising capabilities for assigning glycopeptides to MS data in an automated fashion.
31129958	2	46	theme	creative	170:177	arg1	workflows					179:187	Many creative workflows	165:187	Many creative workflows	165:187	Many creative workflows and software apps have emerged recently that offer promising capabilities for assigning glycopeptides to MS data in an automated fashion.
31129958	6	47	theme	glycopeptide	997:1008	arg1	targets					1010:1016	80 glycopeptide targets	994:1016	80 glycopeptide targets	994:1016	We demonstrate the tool's efficiency by applying it to a set of 80 glycopeptide targets.
31129958	0	48	theme	Glycopeptide	44:55	arg1	Generator					57:65	An On-Demand, De Novo Decoy Glycopeptide Generator	16:65	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.	0:66	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.
31129958	0	49	dep	DecoyDeveloper	0:13	arg1	Generator					57:65	An On-Demand, De Novo Decoy Glycopeptide Generator	16:65	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.	0:66	DecoyDeveloper: An On-Demand, De Novo Decoy Glycopeptide Generator.
31129958	3	50	theme	correct	490:496	arg1	assignment					498:507	its correct assignment	486:507	its correct assignment	486:507	The effectiveness of these tools is best measured and improved by determining how often they would select a glycopeptide decoy as a spectral match, instead of its correct assignment; yet generating the appropriate number and type of glycopeptide decoys can be challenging.
30223526	0	0	theme	Disease	70:76	arg1	Profile					44:50	the Microbial Profile	30:50	the Microbial Profile of Cholelithiasis Disease	30:76	Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
30223526	8	1	theme	Escherichia‒Shigella	1491:1510	arg1	abundance					1406:1414	the abundance	1402:1414	the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella	1402:1510	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	7	2	theme	sauces	1003:1008	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	2	theme	sauces	1003:1008	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	8	3	theme	several	1336:1342	arg1	types					1344:1348	several types	1336:1348	several types of fiber, phenolics, and fatty acids	1336:1385	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	7	4	theme	greater	913:919	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	1	5	theme	certain	225:231	arg1	pathologies					233:243	certain pathologies	225:243	certain pathologies	225:243	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	0	6	theme	Cholelithiasis	55:68	arg1	Disease					70:76	Cholelithiasis Disease	55:76	Cholelithiasis Disease	55:76	Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
30223526	3	7	from	important	366:374	arg1	cholelithiasis					379:392	cholelithiasis	379:392	cholelithiasis	379:392	This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities.
30223526	7	8	theme	vitamin	1119:1125	arg1	C					1127:1127	vitamin C	1119:1127	vitamin C	1119:1127	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	8	theme	vitamin	1119:1125	arg1	folate					1091:1096	folate	1091:1096	folate	1091:1096	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	6	9	theme	sequences	826:834	arg1	quantification					785:798	quantification	785:798	quantification of gallbladder microbiota sequences	785:834	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	6	9	theme	sequences	826:834	arg1	questionnaire					767:779	a food frequency questionnaire	750:779	a food frequency questionnaire	750:779	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	3	10	theme	gallbladder	457:467	arg1	communities					479:489	gallbladder microbial communities	457:489	gallbladder microbial communities	457:489	This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities.
30223526	7	11	theme	cholelithiasic	882:895	arg1	patients					897:904	The cholelithiasic patients	878:904	The cholelithiasic patients	878:904	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	1	12	theme	pathologies	233:243	arg1	prevalence					211:220	the increasing prevalence	196:220	the increasing prevalence of certain pathologies	196:243	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	2	13	from	influence	293:301	arg1	microbiota					346:355	the gut microbiota	338:355	the gut microbiota	338:355	However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota.
30223526	2	13	from	influence	293:301	arg1	microbiotas					314:324	microbiotas	314:324	microbiotas	314:324	However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota.
30223526	9	14	theme	biliary	1556:1562	arg1	microbiota					1564:1573	biliary microbiota	1556:1573	biliary microbiota	1556:1573	These results support a link between diet, biliary microbiota, and cholelithiasis.
30223526	8	15	theme	Bacteroides	1474:1484	arg1	abundance					1406:1414	the abundance	1402:1414	the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella	1402:1510	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	6	16	theme	gallbladder	803:813	arg1	sequences					826:834	gallbladder microbiota sequences	803:834	gallbladder microbiota sequences	803:834	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	4	17	theme	dietary	546:552	arg1	intake					554:559	regular dietary intake	538:559	regular dietary intake	538:559	Our aim was to assess the association between regular dietary intake and gallbladder microbial composition.
30223526	5	18	with	adults	609:614	arg1	sex‒age-matched					653:667	sex‒age-matched	653:667	sex‒age-matched	653:667	Fourteen adults with cholelithiasis and 14 controls, sex‒age-matched and without gastrointestinal pathology, were included.
30223526	5	18	with	adults	609:614	arg1	cholelithiasis					621:634	cholelithiasis	621:634	cholelithiasis	621:634	Fourteen adults with cholelithiasis and 14 controls, sex‒age-matched and without gastrointestinal pathology, were included.
30223526	7	19	theme	non-alcoholic	977:989	arg1	drinks					991:996	non-alcoholic drinks	977:996	non-alcoholic drinks	977:996	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	2	20	theme	little	255:260	arg1	attention					262:270	little attention	255:270	little attention	255:270	However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota.
30223526	1	21	theme	composition	163:173	arg1	shaping					133:139	the shaping	129:139	the shaping of the gut microbiota composition	129:173	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	1	22	theme	gut	148:150	arg1	composition					163:173	the gut microbiota composition	144:173	the gut microbiota composition	144:173	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	4	23	theme	regular	538:544	arg1	intake					554:559	regular dietary intake	538:559	regular dietary intake	538:559	Our aim was to assess the association between regular dietary intake and gallbladder microbial composition.
30223526	2	24	dep	other	327:331	arg1	than					333:336	than	333:336	than	333:336	However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota.
30223526	1	25	theme	microbiota	152:161	arg1	composition					163:173	the gut microbiota composition	144:173	the gut microbiota composition	144:173	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	8	26	theme	altered	1173:1179	arg1	microorganisms					1186:1199	the altered bile microorganisms	1169:1199	the altered bile microorganisms in cholelithiasic patients	1169:1226	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	7	27	theme	vegetables	965:974	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	27	theme	vegetables	965:974	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	2	28	theme	gut	342:344	arg1	microbiota					346:355	the gut microbiota	338:355	the gut microbiota	338:355	However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota.
30223526	7	29	theme	folate	1091:1096	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	29	theme	folate	1091:1096	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	30	theme	lower	944:948	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	1	31	theme	Recent	79:84	arg1	habits					94:99	Recent dietary habits	79:99	Recent dietary habits	79:99	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	7	32	theme	phenolic	1139:1146	arg1	compounds					1148:1156	some phenolic compounds	1134:1156	some phenolic compounds	1134:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	5	33	theme	gastrointestinal	681:696	arg1	pathology					698:706	gastrointestinal pathology	681:706	gastrointestinal pathology	681:706	Fourteen adults with cholelithiasis and 14 controls, sex‒age-matched and without gastrointestinal pathology, were included.
30223526	6	34	theme	frequency	757:765	arg1	questionnaire					767:779	a food frequency questionnaire	750:779	a food frequency questionnaire	750:779	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	1	35	theme	dietary	86:92	arg1	habits					94:99	Recent dietary habits	79:99	Recent dietary habits	79:99	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	7	36	theme	drinks	991:996	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	36	theme	drinks	991:996	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	37	theme	compounds	1148:1156	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	37	theme	compounds	1148:1156	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	38	theme	polysaccharides	1074:1088	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	38	theme	polysaccharides	1074:1088	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	8	39	theme	acids	1381:1385	arg1	types					1344:1348	several types	1336:1348	several types of fiber, phenolics, and fatty acids	1336:1385	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	8	40	theme	cholelithiasic	1204:1217	arg1	patients					1219:1226	cholelithiasic patients	1204:1226	cholelithiasic patients	1204:1226	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	7	41	theme	lipids	1055:1060	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	41	theme	lipids	1055:1060	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	8	42	theme	bile	1181:1184	arg1	microorganisms					1186:1199	the altered bile microorganisms	1169:1199	the altered bile microorganisms in cholelithiasic patients	1169:1226	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	8	43	theme	product	1235:1241	arg1	intake					1243:1248	dairy product intake	1229:1248	dairy product intake	1229:1248	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	8	44	theme	Propionibacteraceae	1453:1471	arg1	abundance					1406:1414	the abundance	1402:1414	the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella	1402:1510	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	8	45	attach	linked	1392:1397	arg2	types					1344:1348	several types	1336:1348	several types of fiber, phenolics, and fatty acids	1336:1385	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	8	45	attach	linked	1392:1397	arg1	abundance					1406:1414	the abundance	1402:1414	the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella	1402:1510	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	3	46	from	changes	406:412	arg1	production					421:430	the production	417:430	the production of bile acids	417:444	This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities.
30223526	8	47	theme	Bacteroidaceae	1300:1313	arg1	proportions					1285:1295	the proportions	1281:1295	the proportions of Bacteroidaceae and Bacteroides	1281:1329	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	0	48	theme	Microbial	34:42	arg1	Profile					44:50	the Microbial Profile	30:50	the Microbial Profile of Cholelithiasis Disease	30:76	Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
30223526	7	49	theme	energy	1047:1052	arg1	intake					1037:1042	a lower intake	1029:1042	a lower intake of energy	1029:1052	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	6	50	theme	gene-based	857:866	arg1	analysis					868:875	Illumina 16S rRNA gene-based analysis	839:875	Illumina 16S rRNA gene-based analysis	839:875	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	7	51	theme	lower	1031:1035	arg1	intake					1037:1042	a lower intake	1029:1042	a lower intake of energy	1029:1052	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	3	52	theme	acids	440:444	arg1	production					421:430	the production	417:430	the production of bile acids	417:444	This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities.
30223526	7	53	theme	digestible	1063:1072	arg1	polysaccharides					1074:1088	digestible polysaccharides	1063:1088	digestible polysaccharides	1063:1088	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	6	54	theme	rRNA	852:855	arg1	analysis					868:875	Illumina 16S rRNA gene-based analysis	839:875	Illumina 16S rRNA gene-based analysis	839:875	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	2	55	theme	diet	306:309	arg1	influence					293:301	the influence	289:301	the influence of diet on microbiotas, other than the gut microbiota	289:355	However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota.
30223526	7	56	theme	potatoes	931:938	arg1	consumption					950:960	lower consumption	944:960	lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds	944:1156	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	7	56	theme	potatoes	931:938	arg1	intake					921:926	greater intake	913:926	greater intake of potatoes	913:938	The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds.
30223526	6	57	theme	16S	848:850	arg1	analysis					868:875	Illumina 16S rRNA gene-based analysis	839:875	Illumina 16S rRNA gene-based analysis	839:875	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	8	58	theme	phenolics	1360:1368	arg1	types					1344:1348	several types	1336:1348	several types of fiber, phenolics, and fatty acids	1336:1385	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	6	59	theme	microbiota	815:824	arg1	sequences					826:834	gallbladder microbiota sequences	803:834	gallbladder microbiota sequences	803:834	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	8	60	theme	Chitinophagaceae	1435:1450	arg1	abundance					1406:1414	the abundance	1402:1414	the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella	1402:1510	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	8	61	theme	fatty	1375:1379	arg1	acids					1381:1385	fatty acids	1375:1385	fatty acids	1375:1385	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	4	62	theme	gallbladder	565:575	arg1	composition					587:597	gallbladder microbial composition	565:597	gallbladder microbial composition	565:597	Our aim was to assess the association between regular dietary intake and gallbladder microbial composition.
30223526	8	63	theme	fiber	1353:1357	arg1	types					1344:1348	several types	1336:1348	several types of fiber, phenolics, and fatty acids	1336:1385	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	6	64	theme	Illumina	839:846	arg1	analysis					868:875	Illumina 16S rRNA gene-based analysis	839:875	Illumina 16S rRNA gene-based analysis	839:875	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	6	65	theme	food	752:755	arg1	questionnaire					767:779	a food frequency questionnaire	750:779	a food frequency questionnaire	750:779	Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis.
30223526	3	66	from	cholelithiasis	379:392	arg1	important					366:374	important	366:374	important	366:374	This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities.
30223526	3	67	theme	bile	435:438	arg1	acids					440:444	bile acids	435:444	bile acids	435:444	This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities.
30223526	1	68	theme	increasing	200:209	arg1	prevalence					211:220	the increasing prevalence	196:220	the increasing prevalence of certain pathologies	196:243	Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies.
30223526	3	69	theme	microbial	469:477	arg1	communities					479:489	gallbladder microbial communities	457:489	gallbladder microbial communities	457:489	This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities.
30223526	8	70	theme	dairy	1229:1233	arg1	intake					1243:1248	dairy product intake	1229:1248	dairy product intake	1229:1248	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	0	71	theme	Profile	44:50	arg1	Cause					6:10	Cause	6:10	Cause	6:10	Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
30223526	0	71	theme	Profile	44:50	arg1	Consequence					15:25	Consequence	15:25	Consequence	15:25	Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
30223526	8	72	from	microorganisms	1186:1199	arg1	patients					1219:1226	cholelithiasic patients	1204:1226	cholelithiasic patients	1204:1226	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	0	73	dep	Diet	0:3	arg1	Cause					6:10	Cause	6:10	Cause	6:10	Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
30223526	0	73	dep	Diet	0:3	arg1	Consequence					15:25	Consequence	15:25	Consequence	15:25	Diet: Cause or Consequence of the Microbial Profile of Cholelithiasis Disease?
30223526	8	74	theme	Bacteroides	1319:1329	arg1	proportions					1285:1295	the proportions	1281:1295	the proportions of Bacteroidaceae and Bacteroides	1281:1329	Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella.
30223526	4	75	theme	microbial	577:585	arg1	composition					587:597	gallbladder microbial composition	565:597	gallbladder microbial composition	565:597	Our aim was to assess the association between regular dietary intake and gallbladder microbial composition.
30979007	2	0	theme	cellular	343:350	arg1	localization					352:363	cellular localization	343:363	cellular localization	343:363	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	8	1	theme	carbohydrate	1654:1665	arg1	chain					1672:1676	the carbohydrate side chain	1650:1676	the carbohydrate side chain	1650:1676	Cleavage of the carbohydrate side chain did not modify CB receptor binding affinity.
30979007	8	2	theme	chain	1672:1676	arg1	Cleavage					1638:1645	Cleavage	1638:1645	Cleavage of the carbohydrate side chain	1638:1676	Cleavage of the carbohydrate side chain did not modify CB receptor binding affinity.
30979007	3	3	theme	SH-SY5Y	698:704	arg1	cells					706:710	SH-SY5Y cells	698:710	SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively	698:886	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	7	4	with	co-localization	1465:1479	arg1	residues					1500:1507	GlcNAc residues	1493:1507	GlcNAc residues	1493:1507	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	3	5	theme	real-time	737:745	arg1	qRT-PCR					796:802	qRT-PCR	796:802	qRT-PCR	796:802	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	5	theme	real-time	737:745	arg1	reaction					786:793	quantitative real-time reverse transcriptase-polymerase chain reaction	724:793	quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)	724:803	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	8	6	theme	CB	1693:1694	arg1	affinity					1713:1720	CB receptor binding affinity	1693:1720	CB receptor binding affinity	1693:1720	Cleavage of the carbohydrate side chain did not modify CB receptor binding affinity.
30979007	4	7	dep	receptors	948:956	arg1	receptors					948:956	type-2 cannabinoid receptors	929:956	type-2 cannabinoid receptors (CB₁ and CB₂)	929:970	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	4	7	dep	receptors	948:956	arg1	CB₂					967:969	CB₂	967:969	CB₂	967:969	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	4	7	dep	receptors	948:956	arg1	CB₁					959:961	CB₁	959:961	CB₁	959:961	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	5	8	theme	gene	1042:1045	arg1	expression					1059:1068	gene and protein expression	1042:1068	expression	1059:1068	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	2	9	theme	neuroblastoma	280:292	arg1	cells					302:306	human neuroblastoma SH-SY5Y cells	274:306	human neuroblastoma SH-SY5Y cells	274:306	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	8	10	theme	binding	1705:1711	arg1	affinity					1713:1720	CB receptor binding affinity	1693:1720	CB receptor binding affinity	1693:1720	Cleavage of the carbohydrate side chain did not modify CB receptor binding affinity.
30979007	6	11	theme	cell	1286:1289	arg1	membranes					1291:1299	cell membranes	1286:1299	cell membranes derived from SH-SY5Y cells	1286:1326	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	5	12	theme	protein	1051:1057	arg1	expression					1059:1068	gene and protein expression	1042:1068	expression	1059:1068	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	1	13	theme	glycosylation	213:225	arg1	effect					203:208	the effect	199:208	the effect of glycosylation	199:225	Endocannabinoid (eCB)-binding receptors can be modulated by several ligands and membrane environment, yet the effect of glycosylation remains to be assessed.
30979007	7	14	theme	marked	1577:1582	arg1	localization					1592:1603	a marked nuclear localization	1575:1603	a marked nuclear localization	1575:1603	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	3	15	theme	transcriptase-polymerase	755:778	arg1	qRT-PCR					796:802	qRT-PCR	796:802	qRT-PCR	796:802	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	15	theme	transcriptase-polymerase	755:778	arg1	reaction					786:793	quantitative real-time reverse transcriptase-polymerase chain reaction	724:793	quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)	724:803	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	16	with	treatment	452:460	arg1	tunicamycin					467:477	tunicamycin	467:477	tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL	467:563	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	7	17	theme	membrane	1550:1557	arg1	expression					1559:1568	CB₁ membrane expression	1546:1568	CB₁ membrane expression	1546:1568	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	3	18	theme	confocal	854:861	arg1	microscopy					863:872	confocal microscopy	854:872	confocal microscopy	854:872	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	4	19	theme	binding	1003:1009	arg1	assays					1011:1016	rapid binding assays	997:1016	rapid binding assays	997:1016	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	1	20	theme	several	153:159	arg1	ligands					161:167	several ligands	153:167	several ligands	153:167	Endocannabinoid (eCB)-binding receptors can be modulated by several ligands and membrane environment, yet the effect of glycosylation remains to be assessed.
30979007	3	21	from	dose	549:552	arg1	tunicamycin					467:477	tunicamycin	467:477	tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL	467:563	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	4	22	theme	cannabinoid	936:946	arg1	receptors					948:956	type-2 cannabinoid receptors	929:956	type-2 cannabinoid receptors (CB₁ and CB₂)	929:970	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	4	22	theme	cannabinoid	936:946	arg1	CB₂					967:969	CB₂	967:969	CB₂	967:969	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	4	22	theme	cannabinoid	936:946	arg1	CB₁					959:961	CB₁	959:961	CB₁	959:961	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	0	23	from	Modulation	0:9	arg1	Cells					71:75	Human Neuroblastoma Cells	51:75	Human Neuroblastoma Cells	51:75	Modulation of Endocannabinoid-Binding Receptors in Human Neuroblastoma Cells by Tunicamycin.
30979007	3	24	theme	cell	829:832	arg1	sorting					834:840	fluorescence-activated cell sorting	806:840	fluorescence-activated cell sorting (FACS)	806:847	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	24	theme	cell	829:832	arg1	FACS					843:846	FACS	843:846	FACS	843:846	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	2	25	theme	receptors	394:402	arg1	expression					331:340	expression	331:340	expression	331:340	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	2	25	theme	receptors	394:402	arg1	localization					352:363	cellular localization	343:363	cellular localization	343:363	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	2	25	theme	receptors	394:402	arg1	activity					370:377	activity	370:377	activity	370:377	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	6	26	theme	SH-SY5Y	1314:1320	arg1	cells					1322:1326	SH-SY5Y cells	1314:1326	SH-SY5Y cells	1314:1326	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	4	27	theme	rapid	997:1001	arg1	assays					1011:1016	rapid binding assays	997:1016	rapid binding assays	997:1016	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	5	28	from	changes	1031:1037	arg1	expression					1059:1068	gene and protein expression	1042:1068	expression	1059:1068	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	2	29	theme	N-linked	418:425	arg1	glycosylation					427:439	N-linked glycosylation	418:439	N-linked glycosylation	418:439	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	0	30	theme	Endocannabinoid-Binding	14:36	arg1	Receptors					38:46	Endocannabinoid-Binding Receptors	14:46	Endocannabinoid-Binding Receptors	14:46	Modulation of Endocannabinoid-Binding Receptors in Human Neuroblastoma Cells by Tunicamycin.
30979007	5	31	theme	GPR55	1140:1144	arg1	receptors					1146:1154	GPR55 receptors	1140:1154	GPR55 receptors	1140:1154	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	7	32	theme	GlcNAc	1493:1498	arg1	residues					1500:1507	GlcNAc residues	1493:1507	GlcNAc residues	1493:1507	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	1	33	theme	-binding	114:121	arg1	receptors					123:131	Endocannabinoid (eCB)-binding receptors	93:131	Endocannabinoid (eCB)-binding receptors	93:131	Endocannabinoid (eCB)-binding receptors can be modulated by several ligands and membrane environment, yet the effect of glycosylation remains to be assessed.
30979007	9	34	theme	post-translational	1797:1814	arg1	modification					1816:1827	an unprecedented post-translational modification	1780:1827	an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁	1780:1919	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	9	34	theme	post-translational	1797:1814	arg1	glycosylation					1763:1775	N-linked glycosylation	1754:1775	N-linked glycosylation	1754:1775	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	3	35	theme	N-acetylglucosamine	641:659	arg1	residues					670:677	N-acetylglucosamine (GlcNAc) residues	641:677	N-acetylglucosamine (GlcNAc) residues	641:677	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	7	36	theme	CB₁	1484:1486	arg1	co-localization					1465:1479	the co-localization	1461:1479	the co-localization of CB₁ with GlcNAc residues	1461:1507	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	0	37	theme	Neuroblastoma	57:69	arg1	Cells					71:75	Human Neuroblastoma Cells	51:75	Human Neuroblastoma Cells	51:75	Modulation of Endocannabinoid-Binding Receptors in Human Neuroblastoma Cells by Tunicamycin.
30979007	3	38	theme	eCB-binding	607:617	arg1	receptors					619:627	eCB-binding receptors	607:627	eCB-binding receptors	607:627	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	39	theme	residues	670:677	arg1	localization					591:602	localization	591:602	localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues,	591:678	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	39	theme	residues	670:677	arg1	mRNA					566:569	mRNA	566:569	mRNA	566:569	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	39	theme	residues	670:677	arg1	levels					580:585	protein levels	572:585	protein levels	572:585	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	40	theme	specific	482:489	arg1	inhibitor					491:499	a specific inhibitor	480:499	a specific inhibitor of N-linked glycosylation	480:525	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	5	41	theme	transient	1169:1177	arg1	TRPV1					1211:1215	TRPV1	1211:1215	TRPV1	1211:1215	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	5	41	theme	transient	1169:1177	arg1	vanilloid					1198:1206	transient receptor potential vanilloid 1	1169:1208	transient receptor potential vanilloid 1 (TRPV1)	1169:1216	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	6	42	gly	glycosylated	1358:1369	arg1	form					1371:1374	one glycosylated form	1354:1374	one glycosylated form	1354:1374	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	3	43	theme	GlcNAc	662:667	arg1	residues					670:677	N-acetylglucosamine (GlcNAc) residues	641:677	N-acetylglucosamine (GlcNAc) residues	641:677	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	6	44	with	experiments	1235:1245	arg1	immunoblot					1272:1281	immunoblot	1272:1281	immunoblot	1272:1281	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	6	44	with	experiments	1235:1245	arg1	N-glycosidase-F					1252:1266	N-glycosidase-F	1252:1266	N-glycosidase-F	1252:1266	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	5	45	theme	potential	1188:1196	arg1	TRPV1					1211:1215	TRPV1	1211:1215	TRPV1	1211:1215	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	5	45	theme	potential	1188:1196	arg1	vanilloid					1198:1206	transient receptor potential vanilloid 1	1169:1208	transient receptor potential vanilloid 1 (TRPV1)	1169:1216	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	7	46	theme	Morphological	1426:1438	arg1	studies					1440:1446	Morphological studies	1426:1446	Morphological studies	1426:1446	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	6	47	attach	derived	1301:1307	arg2	membranes					1291:1299	cell membranes	1286:1299	cell membranes derived from SH-SY5Y cells	1286:1326	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	6	47	attach	derived	1301:1307	arg1	cells					1322:1326	SH-SY5Y cells	1314:1326	SH-SY5Y cells	1314:1326	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	3	48	theme	glycosylation	513:525	arg1	inhibitor					491:499	a specific inhibitor	480:499	a specific inhibitor of N-linked glycosylation	480:525	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	2	49	used	used	269:272	arg2	we					266:267	we	266:267	we	266:267	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	6	50	theme	Deglycosylation	1219:1233	arg1	experiments					1235:1245	Deglycosylation experiments	1219:1245	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells	1219:1326	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	2	51	theme	human	274:278	arg1	cells					302:306	human neuroblastoma SH-SY5Y cells	274:306	human neuroblastoma SH-SY5Y cells	274:306	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	9	52	link	N-linked	1754:1761	arg1	modification					1816:1827	an unprecedented post-translational modification	1780:1827	an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁	1780:1919	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	9	52	link	N-linked	1754:1761	arg1	glycosylation					1763:1775	N-linked glycosylation	1754:1775	N-linked glycosylation	1754:1775	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	3	53	theme	non-cytotoxic	535:547	arg1	dose					549:552	the non-cytotoxic dose	531:552	the non-cytotoxic dose of 1 µg/mL	531:563	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	8	54	theme	side	1667:1670	arg1	chain					1672:1676	the carbohydrate side chain	1650:1676	the carbohydrate side chain	1650:1676	Cleavage of the carbohydrate side chain did not modify CB receptor binding affinity.
30979007	1	55	theme	membrane	173:180	arg1	environment					182:192	membrane environment	173:192	membrane environment	173:192	Endocannabinoid (eCB)-binding receptors can be modulated by several ligands and membrane environment, yet the effect of glycosylation remains to be assessed.
30979007	6	56	theme	form	1371:1374	arg1	presence					1342:1349	the presence	1338:1349	the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin	1338:1423	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	3	57	theme	reverse	747:753	arg1	qRT-PCR					796:802	qRT-PCR	796:802	qRT-PCR	796:802	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	57	theme	reverse	747:753	arg1	reaction					786:793	quantitative real-time reverse transcriptase-polymerase chain reaction	724:793	quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)	724:803	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	2	58	theme	SH-SY5Y	294:300	arg1	cells					302:306	human neuroblastoma SH-SY5Y cells	274:306	human neuroblastoma SH-SY5Y cells	274:306	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	7	59	theme	nuclear	1584:1590	arg1	localization					1592:1603	a marked nuclear localization	1575:1603	a marked nuclear localization	1575:1603	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	3	60	theme	quantitative	724:735	arg1	qRT-PCR					796:802	qRT-PCR	796:802	qRT-PCR	796:802	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	60	theme	quantitative	724:735	arg1	reaction					786:793	quantitative real-time reverse transcriptase-polymerase chain reaction	724:793	quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)	724:803	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	6	61	theme	membranes	1291:1299	arg1	immunoblot					1272:1281	immunoblot	1272:1281	immunoblot	1272:1281	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	6	61	theme	membranes	1291:1299	arg1	N-glycosidase-F					1252:1266	N-glycosidase-F	1252:1266	N-glycosidase-F	1252:1266	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	8	62	theme	receptor	1696:1703	arg1	affinity					1713:1720	CB receptor binding affinity	1693:1720	CB receptor binding affinity	1693:1720	Cleavage of the carbohydrate side chain did not modify CB receptor binding affinity.
30979007	4	63	theme	type-1	918:923	arg1	activity					906:913	the activity	902:913	the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂)	902:970	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	3	64	theme	protein	572:578	arg1	levels					580:585	protein levels	572:585	protein levels	572:585	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	65	theme	chain	780:784	arg1	qRT-PCR					796:802	qRT-PCR	796:802	qRT-PCR	796:802	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	65	theme	chain	780:784	arg1	reaction					786:793	quantitative real-time reverse transcriptase-polymerase chain reaction	724:793	quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)	724:803	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	5	66	theme	Significant	1019:1029	arg1	changes					1031:1037	Significant changes	1019:1037	Significant changes in gene and protein expression	1019:1068	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	3	67	theme	receptors	619:627	arg1	localization					591:602	localization	591:602	localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues,	591:678	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	67	theme	receptors	619:627	arg1	mRNA					566:569	mRNA	566:569	mRNA	566:569	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	67	theme	receptors	619:627	arg1	levels					580:585	protein levels	572:585	protein levels	572:585	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	68	theme	µg/mL	559:563	arg1	dose					549:552	the non-cytotoxic dose	531:552	the non-cytotoxic dose of 1 µg/mL	531:563	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	7	69	theme	CB₁	1546:1548	arg1	expression					1559:1568	CB₁ membrane expression	1546:1568	CB₁ membrane expression	1546:1568	Morphological studies demonstrated the co-localization of CB₁ with GlcNAc residues, and showed that tunicamycin reduced CB₁ membrane expression with a marked nuclear localization, as confirmed by immunoblotting.
30979007	3	70	link	N-linked	504:511	arg1	glycosylation					513:525	N-linked glycosylation	504:525	N-linked glycosylation	504:525	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	71	theme	fluorescence-activated	806:827	arg1	sorting					834:840	fluorescence-activated cell sorting	806:840	fluorescence-activated cell sorting (FACS)	806:847	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	3	71	theme	fluorescence-activated	806:827	arg1	FACS					843:846	FACS	843:846	FACS	843:846	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	6	72	theme	glycosylated	1358:1369	arg1	form					1371:1374	one glycosylated form	1354:1374	one glycosylated form	1354:1374	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	6	73	from	presence	1342:1349	arg1	CB₁					1379:1381	CB₁	1379:1381	CB₁ (70 kDa)	1379:1390	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	6	73	from	presence	1342:1349	arg1	kDa					1387:1389	70 kDa	1384:1389	70 kDa	1384:1389	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	3	74	dep	tunicamycin	467:477	arg1	inhibitor					491:499	a specific inhibitor	480:499	a specific inhibitor of N-linked glycosylation	480:525	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	4	75	theme	type-2	929:934	arg1	receptors					948:956	type-2 cannabinoid receptors	929:956	type-2 cannabinoid receptors (CB₁ and CB₂)	929:970	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	4	75	theme	type-2	929:934	arg1	CB₂					967:969	CB₂	967:969	CB₂	967:969	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	4	75	theme	type-2	929:934	arg1	CB₁					959:961	CB₁	959:961	CB₁	959:961	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	4	76	theme	receptors	948:956	arg1	activity					906:913	the activity	902:913	the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂)	902:970	In addition, the activity of type-1 and type-2 cannabinoid receptors (CB₁ and CB₂) was assessed by means of rapid binding assays.
30979007	2	77	theme	eCB-binding	382:392	arg1	receptors					394:402	eCB-binding receptors	382:402	eCB-binding receptors	382:402	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	5	78	theme	tunicamycin	1086:1096	arg1	treatment					1098:1106	tunicamycin treatment	1086:1106	tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1)	1086:1216	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	6	79	attach	presence	1342:1349	arg1	CB₁					1379:1381	CB₁	1379:1381	CB₁ (70 kDa)	1379:1390	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	6	79	attach	presence	1342:1349	arg2	form					1371:1374	one glycosylated form	1354:1374	one glycosylated form	1354:1374	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	6	79	attach	presence	1342:1349	arg1	kDa					1387:1389	70 kDa	1384:1389	70 kDa	1384:1389	Deglycosylation experiments with N-glycosidase-F and immunoblot of cell membranes derived from SH-SY5Y cells confirmed the presence of one glycosylated form in CB₁ (70 kDa), that was reduced by tunicamycin.
30979007	0	80	theme	Receptors	38:46	arg1	Modulation					0:9	Modulation	0:9	Modulation of Endocannabinoid-Binding Receptors in Human Neuroblastoma Cells by Tunicamycin	0:90	Modulation of Endocannabinoid-Binding Receptors in Human Neuroblastoma Cells by Tunicamycin.
30979007	9	81	theme	unprecedented	1783:1795	arg1	modification					1816:1827	an unprecedented post-translational modification	1780:1827	an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁	1780:1919	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	9	81	theme	unprecedented	1783:1795	arg1	glycosylation					1763:1775	N-linked glycosylation	1754:1775	N-linked glycosylation	1754:1775	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	0	82	theme	Human	51:55	arg1	Cells					71:75	Human Neuroblastoma Cells	51:75	Human Neuroblastoma Cells	51:75	Modulation of Endocannabinoid-Binding Receptors in Human Neuroblastoma Cells by Tunicamycin.
30979007	9	83	theme	N-linked	1754:1761	arg1	modification					1816:1827	an unprecedented post-translational modification	1780:1827	an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁	1780:1919	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	9	83	theme	N-linked	1754:1761	arg1	glycosylation					1763:1775	N-linked glycosylation	1754:1775	N-linked glycosylation	1754:1775	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	3	84	theme	N-linked	504:511	arg1	glycosylation					513:525	N-linked glycosylation	504:525	N-linked glycosylation	504:525	Following treatment with tunicamycin (a specific inhibitor of N-linked glycosylation) at the non-cytotoxic dose of 1 µg/mL, mRNA, protein levels and localization of eCB-binding receptors, as well as N-acetylglucosamine (GlcNAc) residues, were evaluated in SH-SY5Y cells by means of quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), fluorescence-activated cell sorting (FACS), and confocal microscopy, respectively.
30979007	9	85	theme	eCB-binding	1847:1857	arg1	receptors					1859:1867	eCB-binding receptors'	1847:1868	eCB-binding receptors' expression	1847:1879	Overall, these results support N-linked glycosylation as an unprecedented post-translational modification that may modulate eCB-binding receptors' expression and localization, in particular for CB₁.
30979007	2	86	link	N-linked	418:425	arg1	glycosylation					427:439	N-linked glycosylation	418:439	N-linked glycosylation	418:439	In this study, we used human neuroblastoma SH-SY5Y cells to interrogate whether expression, cellular localization, and activity of eCB-binding receptors may depend on N-linked glycosylation.
30979007	5	87	theme	receptor	1179:1186	arg1	TRPV1					1211:1215	TRPV1	1211:1215	TRPV1	1211:1215	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30979007	5	87	theme	receptor	1179:1186	arg1	vanilloid					1198:1206	transient receptor potential vanilloid 1	1169:1208	transient receptor potential vanilloid 1 (TRPV1)	1169:1216	Significant changes in gene and protein expression were found upon tunicamycin treatment for CB₁ and CB₂, as well as for GPR55 receptors, but not for transient receptor potential vanilloid 1 (TRPV1).
30348809	0	0	theme	Oncogenic	76:84	arg1	Effects					86:92	Potent Oncogenic Effects	69:92	Potent Oncogenic Effects	69:92	A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.
30348809	5	1	theme	N610	670:673	arg1	residue					675:681	the N610 residue	666:681	the N610 residue	666:681	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	7	2	theme	Membrane-proximal	850:866	arg1	glycosylation					877:889	Membrane-proximal N-linked glycosylation	850:889	Membrane-proximal N-linked glycosylation	850:889	Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor.
30348809	0	3	theme	Potent	69:74	arg1	Effects					86:92	Potent Oncogenic Effects	69:92	Potent Oncogenic Effects	69:92	A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.
30348809	8	4	theme	CSF3R	1032:1036	arg1	N-glycosylation					1013:1027	membrane-proximal N-glycosylation	995:1027	membrane-proximal N-glycosylation	995:1027	Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion.
30348809	1	5	theme	chronic	230:236	arg1	leukemia					251:258	chronic neutrophilic leukemia	230:258	chronic neutrophilic leukemia	230:258	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	11	6	theme	ligand	1469:1474	arg1	dependency					1476:1485	ligand dependency	1469:1485	ligand dependency	1469:1485	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	1	7	theme	acute	312:316	arg1	leukemia					326:333	acute myeloid leukemia	312:333	acute myeloid leukemia	312:333	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	5	8	theme	Mass	634:637	arg1	spectrometry					639:650	Mass spectrometry	634:650	Mass spectrometry	634:650	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	7	9	theme	receptor	949:956	arg1	dependence					931:940	the ligand dependence	920:940	the ligand dependence of the receptor	920:956	Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor.
30348809	5	10	link	N-linked	706:713	arg1	motif					729:733	a consensus N-linked glycosylation motif	694:733	a consensus N-linked glycosylation motif	694:733	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	1	11	theme	neutrophilic	238:249	arg1	leukemia					251:258	chronic neutrophilic leukemia	230:258	chronic neutrophilic leukemia	230:258	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	5	12	theme	consensus	696:704	arg1	motif					729:733	a consensus N-linked glycosylation motif	694:733	a consensus N-linked glycosylation motif	694:733	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	1	13	theme	myeloid	318:324	arg1	leukemia					326:333	acute myeloid leukemia	312:333	acute myeloid leukemia	312:333	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	14	from	kinds	285:289	arg1	present					268:274	present	268:274	present	268:274	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	11	15	theme	N-linked	1414:1421	arg1	glycosylation					1423:1435	membrane-proximal N-linked glycosylation	1396:1435	membrane-proximal N-linked glycosylation of CSF3R	1396:1444	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	10	16	theme	glycans	1304:1310	arg1	function					1292:1299	the function	1288:1299	the function of glycans in receptor regulation	1288:1333	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	10	17	theme	oncogenic	1197:1205	arg1	mutations					1207:1215	oncogenic mutations	1197:1215	oncogenic mutations in CSF3R that are therapeutically targetable	1197:1260	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	5	18	theme	N-linked	706:713	arg1	motif					729:733	a consensus N-linked glycosylation motif	694:733	a consensus N-linked glycosylation motif	694:733	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	8	19	theme	N610	975:978	arg1	site					980:983	the N610 site	971:983	the N610 site	971:983	Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion.
30348809	1	20	from	present	268:274	arg1	kinds					285:289	other kinds	279:289	other kinds	279:289	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	20	from	present	268:274	arg1	leukemia					326:333	acute myeloid leukemia	312:333	acute myeloid leukemia	312:333	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	5	21	theme	complex	770:776	arg1	glycans					778:784	complex glycans	770:784	complex glycans	770:784	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	11	22	theme	dependency	1476:1485	arg1	maintenance					1454:1464	the maintenance	1450:1464	the maintenance of ligand dependency in leukemia	1450:1497	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	5	23	theme	glycosylation	715:727	arg1	motif					729:733	a consensus N-linked glycosylation motif	694:733	a consensus N-linked glycosylation motif	694:733	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	6	24	theme	receptor	840:847	arg1	sialylation					821:831	sialylation	821:831	sialylation of the receptor	821:847	N610 was also the primary site of sialylation of the receptor.
30348809	8	25	theme	site	980:983	arg1	Mutation					959:966	Mutation	959:966	Mutation of the N610 site	959:983	Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion.
30348809	1	26	attach	present	268:274	arg1	kinds					285:289	other kinds	279:289	other kinds	279:289	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	26	attach	present	268:274	arg2	Mutations					109:117	Mutations	109:117	Mutations in the colony-stimulating factor 3 receptor (CSF3R)	109:169	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	26	attach	present	268:274	arg1	leukemia					326:333	acute myeloid leukemia	312:333	acute myeloid leukemia	312:333	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	0	27	theme	Novel	2:6	arg1	Variant					17:23	A Novel Germline Variant	0:23	A Novel Germline Variant in CSF3R	0:32	A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.
30348809	11	28	theme	membrane-proximal	1396:1412	arg1	glycosylation					1423:1435	membrane-proximal N-linked glycosylation	1396:1435	membrane-proximal N-linked glycosylation of CSF3R	1396:1444	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	8	29	theme	ligand-independent	1056:1073	arg1	expansion					1084:1092	ligand-independent cellular expansion	1056:1092	ligand-independent cellular expansion	1056:1092	Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion.
30348809	7	30	theme	ligand	924:929	arg1	dependence					931:940	the ligand dependence	920:940	the ligand dependence of the receptor	920:956	Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor.
30348809	9	31	theme	Kinase	1095:1100	arg1	inhibitors					1102:1111	Kinase inhibitors	1095:1111	Kinase inhibitors	1095:1111	Kinase inhibitors blocked growth of cells with an N610 mutation.
30348809	8	32	theme	membrane-proximal	995:1011	arg1	N-glycosylation					1013:1027	membrane-proximal N-glycosylation	995:1027	membrane-proximal N-glycosylation	995:1027	Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion.
30348809	5	33	dep	linked	760:765	arg1	part					686:689	part	686:689	part of a consensus N-linked glycosylation motif	686:733	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	6	34	gly	sialylation	821:831	arg1	receptor					840:847	the receptor	836:847	the receptor	836:847	N610 was also the primary site of sialylation of the receptor.
30348809	1	35	from	Mutations	109:117	arg1	CSF3R					164:168	CSF3R	164:168	CSF3R	164:168	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	35	from	Mutations	109:117	arg1	receptor					154:161	the colony-stimulating factor 3 receptor	122:161	the colony-stimulating factor 3 receptor (CSF3R)	122:169	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	5	36	gly	glycosylation	715:727	arg2	motif					729:733	a consensus N-linked glycosylation motif	694:733	a consensus N-linked glycosylation motif	694:733	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	10	37	from	function	1292:1299	arg1	regulation					1324:1333	receptor regulation	1315:1333	receptor regulation	1315:1333	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	2	38	theme	germline	375:382	arg1	variants					384:391	novel germline variants	369:391	novel germline variants	369:391	Here, we studied the function of novel germline variants in CSF3R at amino acid N610.
30348809	0	39	theme	Germline	8:15	arg1	Variant					17:23	A Novel Germline Variant	0:23	A Novel Germline Variant in CSF3R	0:32	A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.
30348809	4	40	theme	signaling	571:579	arg1	pathway					581:587	the JAK-STAT signaling pathway	558:587	the JAK-STAT signaling pathway	558:587	These mutations activated the JAK-STAT signaling pathway and conferred sensitivity to JAK inhibitors.
30348809	3	41	theme	ligand	519:524	arg1	GCSF					526:529	its ligand GCSF	515:529	its ligand GCSF	515:529	These N610 substitutions were potently oncogenic and activated the receptor independently of its ligand GCSF.
30348809	10	42	theme	receptor	1315:1322	arg1	regulation					1324:1333	receptor regulation	1315:1333	receptor regulation	1315:1333	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	2	43	theme	novel	369:373	arg1	variants					384:391	novel germline variants	369:391	novel germline variants	369:391	Here, we studied the function of novel germline variants in CSF3R at amino acid N610.
30348809	11	44	theme	critical	1373:1380	arg1	importance					1382:1391	the critical importance	1369:1391	the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia	1369:1497	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	6	45	theme	sialylation	821:831	arg1	sialylation					821:831	sialylation	821:831	sialylation of the receptor	821:847	N610 was also the primary site of sialylation of the receptor.
30348809	6	45	theme	sialylation	821:831	arg1	site					813:816	the primary site	801:816	the primary site of sialylation of the receptor	801:847	N610 was also the primary site of sialylation of the receptor.
30348809	6	45	theme	sialylation	821:831	arg1	N610					787:790	N610	787:790	N610	787:790	N610 was also the primary site of sialylation of the receptor.
30348809	8	46	theme	cellular	1075:1082	arg1	expansion					1084:1092	ligand-independent cellular expansion	1056:1092	ligand-independent cellular expansion	1056:1092	Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion.
30348809	2	47	from	function	357:364	arg1	CSF3R					396:400	CSF3R	396:400	CSF3R	396:400	Here, we studied the function of novel germline variants in CSF3R at amino acid N610.
30348809	4	48	theme	JAK	618:620	arg1	inhibitors					622:631	JAK inhibitors	618:631	JAK inhibitors	618:631	These mutations activated the JAK-STAT signaling pathway and conferred sensitivity to JAK inhibitors.
30348809	1	49	theme	other	279:283	arg1	kinds					285:289	other kinds	279:289	other kinds	279:289	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	49	theme	other	279:283	arg1	leukemia					326:333	acute myeloid leukemia	312:333	acute myeloid leukemia	312:333	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	10	50	from	repertoire	1183:1192	arg1	CSF3R					1220:1224	CSF3R	1220:1224	CSF3R	1220:1224	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	9	51	theme	cells	1131:1135	arg1	growth					1121:1126	growth	1121:1126	growth of cells	1121:1135	Kinase inhibitors blocked growth of cells with an N610 mutation.
30348809	11	52	theme	CSF3R	1440:1444	arg1	glycosylation					1423:1435	membrane-proximal N-linked glycosylation	1396:1435	membrane-proximal N-linked glycosylation of CSF3R	1396:1444	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	10	53	from	mutations	1207:1215	arg1	CSF3R					1220:1224	CSF3R	1220:1224	CSF3R	1220:1224	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	11	54	theme	glycosylation	1423:1435	arg1	importance					1382:1391	the critical importance	1369:1391	the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia	1369:1497	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	2	55	theme	amino	405:409	arg1	acid					411:414	amino acid N610	405:419	amino acid N610	405:419	Here, we studied the function of novel germline variants in CSF3R at amino acid N610.
30348809	11	56	link	N-linked	1414:1421	arg1	glycosylation					1423:1435	membrane-proximal N-linked glycosylation	1396:1435	membrane-proximal N-linked glycosylation of CSF3R	1396:1444	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	6	57	theme	primary	805:811	arg1	sialylation					821:831	sialylation	821:831	sialylation of the receptor	821:847	N610 was also the primary site of sialylation of the receptor.
30348809	6	57	theme	primary	805:811	arg1	site					813:816	the primary site	801:816	the primary site of sialylation of the receptor	801:847	N610 was also the primary site of sialylation of the receptor.
30348809	6	57	theme	primary	805:811	arg1	N610					787:790	N610	787:790	N610	787:790	N610 was also the primary site of sialylation of the receptor.
30348809	8	58	gly	N-glycosylation	1013:1027	arg1	CSF3R					1032:1036	CSF3R	1032:1036	CSF3R	1032:1036	Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion.
30348809	1	59	theme	leukemia	294:301	arg1	kinds					285:289	other kinds	279:289	other kinds	279:289	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	59	theme	leukemia	294:301	arg1	leukemia					326:333	acute myeloid leukemia	312:333	acute myeloid leukemia	312:333	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	10	60	from	CSF3R	1220:1224	arg1	repertoire					1183:1192	the repertoire	1179:1192	the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable	1179:1260	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	10	60	from	CSF3R	1220:1224	arg1	mutations					1207:1215	oncogenic mutations	1197:1215	oncogenic mutations in CSF3R that are therapeutically targetable	1197:1260	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	11	61	gly	glycosylation	1423:1435	arg1	CSF3R					1440:1444	CSF3R	1440:1444	CSF3R	1440:1444	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	11	62	from	maintenance	1454:1464	arg1	leukemia					1490:1497	leukemia	1490:1497	leukemia	1490:1497	SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
30348809	9	63	theme	N610	1145:1148	arg1	mutation					1150:1157	an N610 mutation	1142:1157	an N610 mutation	1142:1157	Kinase inhibitors blocked growth of cells with an N610 mutation.
30348809	7	64	link	N-linked	868:875	arg1	glycosylation					877:889	Membrane-proximal N-linked glycosylation	850:889	Membrane-proximal N-linked glycosylation	850:889	Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor.
30348809	5	65	attach	linked	760:765	arg1	glycans					778:784	complex glycans	770:784	complex glycans	770:784	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	5	65	attach	linked	760:765	arg2	residue					675:681	the N610 residue	666:681	the N610 residue	666:681	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	5	65	attach	linked	760:765	arg3	receptor					742:749	the receptor	738:749	the receptor	738:749	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	1	66	theme	vast	199:202	arg1	majority					204:211	the vast majority	195:211	the vast majority of patients with chronic neutrophilic leukemia	195:258	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	67	located	present	268:274	arg1	kinds					285:289	other kinds	279:289	other kinds	279:289	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	67	located	present	268:274	arg2	Mutations					109:117	Mutations	109:117	Mutations in the colony-stimulating factor 3 receptor (CSF3R)	109:169	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	67	located	present	268:274	arg1	leukemia					326:333	acute myeloid leukemia	312:333	acute myeloid leukemia	312:333	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	3	68	theme	N610	428:431	arg1	substitutions					433:445	These N610 substitutions	422:445	These N610 substitutions	422:445	These N610 substitutions were potently oncogenic and activated the receptor independently of its ligand GCSF.
30348809	7	69	theme	N-linked	868:875	arg1	glycosylation					877:889	Membrane-proximal N-linked glycosylation	850:889	Membrane-proximal N-linked glycosylation	850:889	Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor.
30348809	4	70	theme	JAK-STAT	562:569	arg1	pathway					581:587	the JAK-STAT signaling pathway	558:587	the JAK-STAT signaling pathway	558:587	These mutations activated the JAK-STAT signaling pathway and conferred sensitivity to JAK inhibitors.
30348809	5	71	theme	motif	729:733	arg1	part					686:689	part	686:689	part of a consensus N-linked glycosylation motif	686:733	Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans.
30348809	1	72	with	patients	216:223	arg1	leukemia					251:258	chronic neutrophilic leukemia	230:258	chronic neutrophilic leukemia	230:258	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	73	theme	colony-stimulating	126:143	arg1	CSF3R					164:168	CSF3R	164:168	CSF3R	164:168	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	73	theme	colony-stimulating	126:143	arg1	receptor					154:161	the colony-stimulating factor 3 receptor	122:161	the colony-stimulating factor 3 receptor (CSF3R)	122:169	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	10	74	theme	mutations	1207:1215	arg1	repertoire					1183:1192	the repertoire	1179:1192	the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable	1179:1260	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	10	74	theme	mutations	1207:1215	arg1	mutations					1207:1215	oncogenic mutations	1197:1215	oncogenic mutations in CSF3R that are therapeutically targetable	1197:1260	This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation.
30348809	0	75	from	Variant	17:23	arg1	CSF3R					28:32	CSF3R	28:32	CSF3R	28:32	A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.
30348809	2	76	theme	variants	384:391	arg1	function					357:364	the function	353:364	the function of novel germline variants in CSF3R	353:400	Here, we studied the function of novel germline variants in CSF3R at amino acid N610.
30348809	1	77	theme	factor	145:150	arg1	CSF3R					164:168	CSF3R	164:168	CSF3R	164:168	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	77	theme	factor	145:150	arg1	receptor					154:161	the colony-stimulating factor 3 receptor	122:161	the colony-stimulating factor 3 receptor (CSF3R)	122:169	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30348809	1	78	theme	patients	216:223	arg1	majority					204:211	the vast majority	195:211	the vast majority of patients with chronic neutrophilic leukemia	195:258	: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia.
30991145	3	0	theme	G	690:690	arg1	glycosylation					700:712	G protein glycosylation	690:712	G protein glycosylation	690:712	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	4	1	theme	quadruple	997:1005	arg1	disruptions					1026:1036	quadruple glycosylation site disruptions	997:1036	quadruple glycosylation site disruptions	997:1036	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	6	2	theme	quadruple	1585:1593	arg1	mutants					1595:1601	the triple and quadruple mutants	1570:1601	the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication	1570:1736	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	0	3	link	N-linked	0:7	arg1	sites					23:27	N-linked glycosylation sites	0:27	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV)	0:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	8	4	theme	immune	2204:2209	arg1	escape					2211:2216	viral immune escape	2198:2216	viral immune escape	2198:2216	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	7	5	dep	%	1878:1878	arg1	100					1875:1877	100	1875:1877	100	1875:1877	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	3	6	theme	IHNV	717:720	arg1	replication					722:732	IHNV replication	717:732	IHNV replication	717:732	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	6	7	theme	triple	1574:1579	arg1	mutants					1595:1601	the triple and quadruple mutants	1570:1601	the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication	1570:1736	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	1	8	theme	necrosis	175:182	arg1	virus					184:188	Infectious hematopoietic necrosis virus	150:188	Infectious hematopoietic necrosis virus (IHNV)	150:195	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	1	8	theme	necrosis	175:182	arg1	IHNV					191:194	IHNV	191:194	IHNV	191:194	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	7	9	theme	%	2025:2025	arg1	mortality					2000:2008	cumulative mortality	1989:2008	cumulative mortality of less than 50%	1989:2025	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	7	10	dep	mortality	1891:1899	arg1	%					1878:1878	%	1878:1878	%	1878:1878	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	8	11	gly	glycosylation	2145:2157	arg1	asparagine					2162:2171	asparagine 438	2162:2175	asparagine 438	2162:2175	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	3	12	theme	glycosylation	571:583	arg1	sites					585:589	viral glycosylation sites	565:589	viral glycosylation sites	565:589	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	9	13	from	effect	2256:2261	arg1	immunogenicity					2315:2328	immunogenicity	2315:2328	immunogenicity	2315:2328	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	9	13	from	effect	2256:2261	arg1	pathogenicity					2297:2309	pathogenicity	2297:2309	pathogenicity	2297:2309	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	4	14	from	substitutions	1052:1064	arg1	combinations					1083:1094	the following combinations	1069:1094	the following combinations	1069:1094	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	7	15	theme	cumulative	1989:1998	arg1	mortality					2000:2008	cumulative mortality	1989:2008	cumulative mortality of less than 50%	1989:2025	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	3	16	gly	glycosylation	571:583	arg2	sites					585:589	viral glycosylation sites	565:589	viral glycosylation sites	565:589	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	0	17	theme	rainbow	135:141	arg1	trout					143:147	rainbow trout	135:147	rainbow trout	135:147	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	6	18	theme	asparagines	1629:1639	arg1	mutation					1617:1624	mutation	1617:1624	mutation of asparagines 401 and 438	1617:1651	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	1	19	from	necrosis	229:236	arg1	fish					250:253	salmonid fish	241:253	salmonid fish	241:253	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	9	20	dep	pathogenicity	2297:2309	arg1	the					2293:2295	the	2293:2295	the	2293:2295	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	0	21	theme	hematopoietic	56:68	arg1	virus					79:83	infectious hematopoietic necrosis virus	45:83	infectious hematopoietic necrosis virus (IHNV)	45:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	0	21	theme	hematopoietic	56:68	arg1	IHNV					86:89	IHNV	86:89	IHNV	86:89	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	7	22	theme	trout	1766:1770	arg1	mortality					1772:1780	juvenile rainbow trout mortality	1749:1780	juvenile rainbow trout mortality after challenge by each of the nine mutants	1749:1824	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	0	23	from	sites	23:27	arg1	protein					34:40	G protein	32:40	G protein of infectious hematopoietic necrosis virus (IHNV)	32:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	0	24	theme	virus	79:83	arg1	protein					34:40	G protein	32:40	G protein of infectious hematopoietic necrosis virus (IHNV)	32:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	4	25	from	Asp	849:851	arg1	protein					862:868	G protein	860:868	G protein	860:868	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	1	26	theme	Infectious	150:159	arg1	virus					184:188	Infectious hematopoietic necrosis virus	150:188	Infectious hematopoietic necrosis virus (IHNV)	150:195	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	1	26	theme	Infectious	150:159	arg1	IHNV					191:194	IHNV	191:194	IHNV	191:194	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	7	27	theme	juvenile	1749:1756	arg1	trout					1766:1770	juvenile rainbow trout	1749:1770	juvenile rainbow trout mortality after challenge by each of the nine mutants	1749:1824	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	4	28	theme	genetics	891:898	arg1	system					900:905	a reverse genetics system	881:905	a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations	881:1094	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	2	29	theme	IHNV	508:511	arg1	immunogenicity					490:503	immunogenicity	490:503	immunogenicity	490:503	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	2	29	theme	IHNV	508:511	arg1	pathogenicity					472:484	pathogenicity	472:484	pathogenicity	472:484	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	9	30	theme	protein	2268:2274	arg1	glycosylation					2276:2288	G protein glycosylation	2266:2288	G protein glycosylation	2266:2288	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	8	31	theme	anti-IHNV	2076:2084	arg1	production					2090:2099	specific anti-IHNV IgM production	2067:2099	specific anti-IHNV IgM production	2067:2099	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	5	32	theme	Western	1368:1374	arg1	blot					1376:1379	Western blot	1368:1379	Western blot	1368:1379	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	2	33	theme	antigenic	375:383	arg1	determinants					385:396	the major antigenic determinants	365:396	the major antigenic determinants of IHNV	365:404	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	0	34	theme	N-linked	0:7	arg1	sites					23:27	N-linked glycosylation sites	0:27	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV)	0:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	1	35	theme	substantial	269:279	arg1	losses					290:295	substantial economic losses	269:295	substantial economic losses to the aquaculture industry worldwide	269:333	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	7	36	theme	alanine	1940:1946	arg1	substitution					1948:1959	a single alanine substitution	1931:1959	a single alanine substitution at position 438	1931:1975	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	9	37	gly	glycosylation	2276:2288	arg1	IHNV					2333:2336	IHNV	2333:2336	IHNV	2333:2336	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	5	38	theme	N-linked	1340:1347	arg1	glycosylation					1349:1361	N-linked glycosylation	1340:1361	N-linked glycosylation	1340:1361	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	0	39	theme	G	32:32	arg1	protein					34:40	G protein	32:40	G protein of infectious hematopoietic necrosis virus (IHNV)	32:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	4	40	gly	glycosylation	795:807	arg2	four					781:784	four	781:784	four	781:784	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	4	40	gly	glycosylation	795:807	arg2	sites					809:813	four N-linked glycosylation sites	781:813	four N-linked glycosylation sites	781:813	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	0	41	gly	glycosylation	9:21	arg2	sites					23:27	N-linked glycosylation sites	0:27	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV)	0:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	7	42	theme	cumulative	1880:1889	arg1	mortality					1891:1899	almost 100% cumulative mortality	1868:1899	almost 100% cumulative mortality	1868:1899	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	4	43	link	N-linked	786:793	arg1	sites					809:813	four N-linked glycosylation sites	781:813	four N-linked glycosylation sites	781:813	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	2	44	theme	important	449:457	arg1	role					459:462	an important role	446:462	an important role	446:462	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	9	45	theme	IHNV	2333:2336	arg1	immunogenicity					2315:2328	immunogenicity	2315:2328	immunogenicity	2315:2328	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	9	45	theme	IHNV	2333:2336	arg1	pathogenicity					2297:2309	pathogenicity	2297:2309	pathogenicity	2297:2309	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	1	46	theme	industry	316:323	arg1	worldwide					325:333	the aquaculture industry worldwide	300:333	the aquaculture industry worldwide	300:333	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	4	47	theme	glycosylation	795:807	arg1	sites					809:813	four N-linked glycosylation sites	781:813	four N-linked glycosylation sites	781:813	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	5	48	theme	N-glycosylation	1423:1437	arg1	mutation					1396:1403	mutation	1396:1403	mutation of each predicted N-glycosylation sited	1396:1443	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	1	49	theme	hematopoietic	215:227	arg1	necrosis					229:236	infectious hematopoietic necrosis	204:236	infectious hematopoietic necrosis in salmonid fish	204:253	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	4	50	theme	alanine	1044:1050	arg1	substitutions					1052:1064	alanine substitutions	1044:1064	alanine substitutions in the following combinations	1044:1094	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	0	51	from	immunogenicity	117:130	arg1	trout					143:147	rainbow trout	135:147	rainbow trout	135:147	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	3	52	theme	specific	664:671	arg1	contributions					673:685	the specific contributions	660:685	the specific contributions of G protein glycosylation to IHNV replication and pathogenicity	660:750	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	8	53	theme	specific	2067:2074	arg1	production					2090:2099	specific anti-IHNV IgM production	2067:2099	specific anti-IHNV IgM production	2067:2099	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	2	54	gly	glycoprotein	422:433	arg1	protein					342:348	The G protein	336:348	The G protein	336:348	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	2	54	gly	glycoprotein	422:433	arg1	glycoprotein					422:433	an envelope glycoprotein	410:433	an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV	410:511	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	8	55	theme	asparagine	2162:2171	arg1	glycosylation					2145:2157	glycosylation	2145:2157	glycosylation of asparagine 438	2145:2175	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	0	56	from	virulence	103:111	arg1	trout					143:147	rainbow trout	135:147	rainbow trout	135:147	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	5	57	gly	glycosylation	1349:1361	arg2	asparagines					1315:1325	all four asparagines	1306:1325	all four asparagines	1306:1325	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	5	57	gly	glycosylation	1349:1361	arg2	glycosylation					1349:1361	N-linked glycosylation	1340:1361	N-linked glycosylation	1340:1361	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	5	57	gly	glycosylation	1349:1361	arg2	sites					1331:1335	sites	1331:1335	sites of N-linked glycosylation	1331:1361	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	6	58	theme	replication	1503:1513	arg1	levels					1515:1520	replication levels	1503:1520	replication levels	1503:1520	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	5	59	link	N-linked	1340:1347	arg1	glycosylation					1349:1361	N-linked glycosylation	1340:1361	N-linked glycosylation	1340:1361	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	4	60	theme	glycosylation	1007:1019	arg1	disruptions					1026:1036	quadruple glycosylation site disruptions	997:1036	quadruple glycosylation site disruptions	997:1036	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	3	61	theme	protein	692:698	arg1	glycosylation					700:712	G protein glycosylation	690:712	G protein glycosylation	690:712	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	9	62	theme	live-attenuated	2381:2395	arg1	vaccine					2397:2403	a live-attenuated vaccine	2379:2403	a live-attenuated vaccine	2379:2403	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	1	63	theme	hematopoietic	161:173	arg1	virus					184:188	Infectious hematopoietic necrosis virus	150:188	Infectious hematopoietic necrosis virus (IHNV)	150:195	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	1	63	theme	hematopoietic	161:173	arg1	IHNV					191:194	IHNV	191:194	IHNV	191:194	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	4	64	with	viruses	965:971	arg1	single					978:983	single	978:983	single	978:983	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	8	65	theme	viral	2198:2202	arg1	escape					2211:2216	viral immune escape	2198:2216	viral immune escape	2198:2216	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	4	66	dep	single	978:983	arg1	triple					986:991	triple	986:991	triple	986:991	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	3	67	theme	viral	565:569	arg1	sites					585:589	viral glycosylation sites	565:589	viral glycosylation sites	565:589	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	4	68	theme	following	1073:1081	arg1	combinations					1083:1094	the following combinations	1069:1094	the following combinations	1069:1094	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	7	69	with	mutant	1919:1924	arg1	substitution					1948:1959	a single alanine substitution	1931:1959	a single alanine substitution at position 438	1931:1975	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	7	70	from	position	1964:1971	arg1	substitution					1948:1959	a single alanine substitution	1931:1959	a single alanine substitution at position 438	1931:1975	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	6	71	theme	efficient	1716:1724	arg1	replication					1726:1736	efficient replication	1716:1736	efficient replication	1716:1736	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	4	72	theme	G	860:860	arg1	protein					862:868	G protein	860:868	G protein	860:868	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	0	73	theme	necrosis	70:77	arg1	virus					79:83	infectious hematopoietic necrosis virus	45:83	infectious hematopoietic necrosis virus (IHNV)	45:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	0	73	theme	necrosis	70:77	arg1	IHNV					86:89	IHNV	86:89	IHNV	86:89	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	4	74	gly	glycosylation	1007:1019	arg2	disruptions					1026:1036	quadruple glycosylation site disruptions	997:1036	quadruple glycosylation site disruptions	997:1036	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	4	74	gly	glycosylation	1007:1019	arg2	site					1021:1024	quadruple glycosylation site disruptions	997:1036	quadruple glycosylation site disruptions	997:1036	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	6	75	theme	glycosylation	1683:1695	arg1	importance					1669:1678	the importance	1665:1678	the importance of glycosylation	1665:1695	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	7	76	theme	rainbow	1758:1764	arg1	trout					1766:1770	juvenile rainbow trout	1749:1770	juvenile rainbow trout mortality after challenge by each of the nine mutants	1749:1824	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	4	77	theme	reverse	883:889	arg1	genetics					891:898	a reverse genetics	881:898	a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations	881:1094	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	5	78	theme	glycosylation	1349:1361	arg1	sites					1331:1335	sites	1331:1335	sites of N-linked glycosylation	1331:1361	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	5	78	theme	glycosylation	1349:1361	arg1	glycosylation					1349:1361	N-linked glycosylation	1340:1361	N-linked glycosylation	1340:1361	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	5	78	theme	glycosylation	1349:1361	arg1	asparagines					1315:1325	all four asparagines	1306:1325	all four asparagines	1306:1325	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	9	79	theme	G	2266:2266	arg1	glycosylation					2276:2288	G protein glycosylation	2266:2288	G protein glycosylation	2266:2288	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	8	80	theme	IgM	2086:2088	arg1	production					2090:2099	specific anti-IHNV IgM production	2067:2099	specific anti-IHNV IgM production	2067:2099	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	9	81	theme	glycosylation	2276:2288	arg1	effect					2256:2261	the effect	2252:2261	the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV	2252:2336	In conclusion, our study reveals the effect of G protein glycosylation on the pathogenicity and immunogenicity of IHNV and provides a foundation for developing a live-attenuated vaccine.
30991145	0	82	theme	glycosylation	9:21	arg1	sites					23:27	N-linked glycosylation sites	0:27	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV)	0:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	7	83	theme	single	1933:1938	arg1	substitution					1948:1959	a single alanine substitution	1931:1959	a single alanine substitution at position 438	1931:1975	Moreover, juvenile rainbow trout mortality after challenge by each of the nine mutants showed that, while eight mutants suffered almost 100% cumulative mortality over 30 days, the mutant with a single alanine substitution at position 438 resulted in cumulative mortality of less than 50% over 30 days.
30991145	2	84	theme	major	369:373	arg1	determinants					385:396	the major antigenic determinants	365:396	the major antigenic determinants of IHNV	365:404	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	1	85	theme	economic	281:288	arg1	losses					290:295	substantial economic losses	269:295	substantial economic losses to the aquaculture industry worldwide	269:333	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	6	86	theme	438	1649:1651	arg1	mutation					1617:1624	mutation	1617:1624	mutation of asparagines 401 and 438	1617:1651	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	8	87	theme	other	2114:2118	arg1	mutants					2120:2126	other mutants	2114:2126	other mutants	2114:2126	This mutant also elicited specific anti-IHNV IgM production earlier than other mutants, suggesting that glycosylation of asparagine 438 may be important for viral immune escape.
30991145	2	88	theme	envelope	413:420	arg1	protein					342:348	The G protein	336:348	The G protein	336:348	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	2	88	theme	envelope	413:420	arg1	glycoprotein					422:433	an envelope glycoprotein	410:433	an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV	410:511	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	2	89	theme	IHNV	401:404	arg1	determinants					385:396	the major antigenic determinants	365:396	the major antigenic determinants of IHNV	365:404	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	0	90	theme	infectious	45:54	arg1	virus					79:83	infectious hematopoietic necrosis virus	45:83	infectious hematopoietic necrosis virus (IHNV)	45:90	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	0	90	theme	infectious	45:54	arg1	IHNV					86:89	IHNV	86:89	IHNV	86:89	N-linked glycosylation sites in G protein of infectious hematopoietic necrosis virus (IHNV) affect its virulence and immunogenicity in rainbow trout.
30991145	1	91	theme	aquaculture	304:314	arg1	worldwide					325:333	the aquaculture industry worldwide	300:333	the aquaculture industry worldwide	300:333	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	4	92	theme	recombinant	953:963	arg1	viruses					965:971	nine recombinant viruses	948:971	nine recombinant viruses with single, triple	948:991	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	5	93	theme	predicted	1413:1421	arg1	N-glycosylation					1423:1437	each predicted N-glycosylation	1408:1437	each predicted N-glycosylation	1408:1437	Our results confirmed that all four asparagines are sites of N-linked glycosylation, and Western blot confirmed that mutation of each predicted N-glycosylation sited impaired glycosylation.
30991145	2	94	theme	G	340:340	arg1	protein					342:348	The G protein	336:348	The G protein	336:348	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	2	94	theme	G	340:340	arg1	glycoprotein					422:433	an envelope glycoprotein	410:433	an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV	410:511	The G protein, which harbors the major antigenic determinants of IHNV, is an envelope glycoprotein that plays an important role in both pathogenicity and immunogenicity of IHNV.
30991145	4	95	theme	site	1021:1024	arg1	disruptions					1026:1036	quadruple glycosylation site disruptions	997:1036	quadruple glycosylation site disruptions	997:1036	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	4	96	theme	N-linked	786:793	arg1	sites					809:813	four N-linked glycosylation sites	781:813	four N-linked glycosylation sites	781:813	In this study, we predicted four N-linked glycosylation sites at position 56, 379, 401, and 438 Asp (N) in G protein, and using a reverse genetics system developed in our laboratory, constructed nine recombinant viruses with single, triple, or quadruple glycosylation site disruptions using alanine substitutions in the following combinations: rIHNV-N56A, rIHNV-N379A, rIHNV-N401A, rIHNV-N438A, rIHNV-N56A-N379A-N401A, rIHNV-N56A-N379A-N438A, rIHNV-N56A-N401A-N438A, rIHNV-N379A-N401A-N438A, and rIHNV-N56A-N379A-N401A-N438A.
30991145	3	97	theme	Previous	514:521	arg1	studies					523:529	Previous studies	514:529	Previous studies	514:529	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	1	98	theme	infectious	204:213	arg1	necrosis					229:236	infectious hematopoietic necrosis	204:236	infectious hematopoietic necrosis in salmonid fish	204:253	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
30991145	3	99	theme	glycosylation	700:712	arg1	contributions					673:685	the specific contributions	660:685	the specific contributions of G protein glycosylation to IHNV replication and pathogenicity	660:750	Previous studies have demonstrated that changes to viral glycosylation sites may affect replication and immunogenicity, but little is known about the specific contributions of G protein glycosylation to IHNV replication and pathogenicity.
30991145	6	100	theme	recombinant	1484:1494	arg1	IHNVs					1496:1500	the nine recombinant IHNVs	1475:1500	the nine recombinant IHNVs	1475:1500	Among the nine recombinant IHNVs, replication levels decreased significantly in vitro and in vivo in the triple and quadruple mutants that combined mutation of asparagines 401 and 438, indicating the importance of glycosylation at these sites for efficient replication.
30991145	1	101	theme	salmonid	241:248	arg1	fish					250:253	salmonid fish	241:253	salmonid fish	241:253	Infectious hematopoietic necrosis virus (IHNV) causes infectious hematopoietic necrosis in salmonid fish, resulting in substantial economic losses to the aquaculture industry worldwide.
29937983	0	0	theme	Protein	98:104	arg1	Profiling					106:114	Activity-Based Protein Profiling	83:114	Activity-Based Protein Profiling	83:114	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling.
29937983	3	1	theme	unusual	333:339	arg1	event					359:363	an unusual O-fatty acylation event	330:363	an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors	330:465	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	3	2	mod	modified	318:325	arg1	Wnts					309:312	Wnts	309:312	Wnts	309:312	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	3	2	mod	modified	318:325	arg3	event					359:363	an unusual O-fatty acylation event	330:363	an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors	330:465	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	1	3	from	development	192:202	arg1	organisms					235:243	adult organisms	229:243	adult organisms	229:243	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	7	4	theme	ABPP	1045:1048	arg1	probe					1050:1054	an ABPP probe	1042:1054	an ABPP probe for visualizing NOTUM in native biological systems	1042:1105	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	0	5	theme	Activity-Based	83:96	arg1	Profiling					106:114	Activity-Based Protein Profiling	83:114	Activity-Based Protein Profiling	83:114	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling.
29937983	7	6	theme	native	1081:1086	arg1	systems					1099:1105	native biological systems	1081:1105	native biological systems	1081:1105	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	6	7	theme	N-hydroxyhydantoin	825:842	arg1	class					816:820	a class	814:820	a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM	814:903	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	6	7	theme	N-hydroxyhydantoin	825:842	arg1	NHH					845:847	NHH	845:847	NHH	845:847	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	4	8	theme	PORCN	528:532	arg1	acyltransferase					535:549	the porcupine (PORCN) acyltransferase	513:549	the porcupine (PORCN) acyltransferase	513:549	O-Palmitoleoylation of Wnts is introduced by the porcupine (PORCN) acyltransferase and removed by the serine hydrolase NOTUM.
29937983	7	9	theme	Wnt-mediated	961:972	arg1	signaling					979:987	Wnt-mediated cell signaling	961:987	Wnt-mediated cell signaling	961:987	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	7	10	from	NOTUM	1072:1076	arg1	systems					1099:1105	native biological systems	1081:1105	native biological systems	1081:1105	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	6	11	theme	class	816:820	arg1	carbamates					850:859	a class of N-hydroxyhydantoin (NHH) carbamates	814:859	a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM	814:903	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	3	12	link	O-linked	366:373	arg1	palmitoleoylation					375:391	O-linked palmitoleoylation	366:391	O-linked palmitoleoylation of a conserved serine	366:413	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	7	13	theme	cell	974:977	arg1	signaling					979:987	Wnt-mediated cell signaling	961:987	Wnt-mediated cell signaling	961:987	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	1	14	theme	embryonic	182:190	arg1	development					192:202	embryonic development	182:202	embryonic development	182:202	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	3	15	theme	O-linked	366:373	arg1	palmitoleoylation					375:391	O-linked palmitoleoylation	366:391	O-linked palmitoleoylation of a conserved serine	366:413	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	7	16	theme	NOTUM	1008:1012	arg1	presence					996:1003	the presence	992:1003	the presence of NOTUM	992:1012	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	0	17	theme	Irreversible	10:21	arg1	Inhibitors					23:32	Selective Irreversible Inhibitors	0:32	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM	0:68	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling.
29937983	3	18	theme	O-fatty	341:347	arg1	event					359:363	an unusual O-fatty acylation event	330:363	an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors	330:465	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	5	19	theme	NOTUM	653:657	arg1	inhibitors					659:668	NOTUM inhibitors	653:668	NOTUM inhibitors	653:668	PORCN inhibitors are under development for oncology, while NOTUM inhibitors have potential for treating degenerative diseases.
29937983	5	20	theme	PORCN	594:598	arg1	inhibitors					600:609	PORCN inhibitors	594:609	PORCN inhibitors	594:609	PORCN inhibitors are under development for oncology, while NOTUM inhibitors have potential for treating degenerative diseases.
29937983	0	21	theme	Selective	0:8	arg1	Inhibitors					23:32	Selective Irreversible Inhibitors	0:32	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM	0:68	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling.
29937983	4	22	theme	serine	570:575	arg1	NOTUM					587:591	the serine hydrolase NOTUM	566:591	the serine hydrolase NOTUM	566:591	O-Palmitoleoylation of Wnts is introduced by the porcupine (PORCN) acyltransferase and removed by the serine hydrolase NOTUM.
29937983	7	23	theme	biological	1088:1097	arg1	systems					1099:1105	native biological systems	1081:1105	native biological systems	1081:1105	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	1	24	theme	tissue	208:213	arg1	remodeling					215:224	tissue remodeling	208:224	tissue remodeling	208:224	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	4	25	theme	porcupine	517:525	arg1	acyltransferase					535:549	the porcupine (PORCN) acyltransferase	513:549	the porcupine (PORCN) acyltransferase	513:549	O-Palmitoleoylation of Wnts is introduced by the porcupine (PORCN) acyltransferase and removed by the serine hydrolase NOTUM.
29937983	1	26	theme	Wnt	117:119	arg1	morphogens					143:152	secreted morphogens	134:152	secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms	134:243	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	1	26	theme	Wnt	117:119	arg1	proteins					121:128	Wnt proteins	117:128	Wnt proteins	117:128	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	3	27	theme	conserved	398:406	arg1	serine					408:413	a conserved serine	396:413	a conserved serine	396:413	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	0	28	theme	Wnt-Deacylating	41:55	arg1	NOTUM					64:68	the Wnt-Deacylating Enzyme NOTUM	37:68	the Wnt-Deacylating Enzyme NOTUM	37:68	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling.
29937983	4	29	theme	hydrolase	577:585	arg1	NOTUM					587:591	the serine hydrolase NOTUM	566:591	the serine hydrolase NOTUM	566:591	O-Palmitoleoylation of Wnts is introduced by the porcupine (PORCN) acyltransferase and removed by the serine hydrolase NOTUM.
29937983	7	30	theme	NHH	919:921	arg1	ABC99					944:948	ABC99	944:948	ABC99	944:948	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	7	30	theme	NHH	919:921	arg1	inhibitor					933:941	An optimized NHH carbamate inhibitor	906:941	An optimized NHH carbamate inhibitor	906:941	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	1	31	theme	adult	229:233	arg1	organisms					235:243	adult organisms	229:243	adult organisms	229:243	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	3	32	theme	Frizzled	448:455	arg1	receptors					457:465	Frizzled receptors	448:465	Frizzled receptors	448:465	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	3	33	dep	event	359:363	arg1	palmitoleoylation					375:391	O-linked palmitoleoylation	366:391	O-linked palmitoleoylation of a conserved serine	366:413	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	4	34	theme	Wnts	491:494	arg1	O-Palmitoleoylation					468:486	O-Palmitoleoylation	468:486	O-Palmitoleoylation of Wnts	468:494	O-Palmitoleoylation of Wnts is introduced by the porcupine (PORCN) acyltransferase and removed by the serine hydrolase NOTUM.
29937983	2	35	theme	Wnt	255:257	arg1	signaling					259:267	Aberrant Wnt signaling	246:267	Aberrant Wnt signaling	246:267	Aberrant Wnt signaling contributes to diseases such as cancer.
29937983	0	36	theme	NOTUM	64:68	arg1	Inhibitors					23:32	Selective Irreversible Inhibitors	0:32	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM	0:68	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling.
29937983	5	37	theme	degenerative	698:709	arg1	diseases					711:718	degenerative diseases	698:718	degenerative diseases	698:718	PORCN inhibitors are under development for oncology, while NOTUM inhibitors have potential for treating degenerative diseases.
29937983	2	38	theme	Aberrant	246:253	arg1	signaling					259:267	Aberrant Wnt signaling	246:267	Aberrant Wnt signaling	246:267	Aberrant Wnt signaling contributes to diseases such as cancer.
29937983	0	39	theme	Enzyme	57:62	arg1	NOTUM					64:68	the Wnt-Deacylating Enzyme NOTUM	37:68	the Wnt-Deacylating Enzyme NOTUM	37:68	Selective Irreversible Inhibitors of the Wnt-Deacylating Enzyme NOTUM Developed by Activity-Based Protein Profiling.
29937983	1	40	from	remodeling	215:224	arg1	organisms					235:243	adult organisms	229:243	adult organisms	229:243	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	1	41	theme	secreted	134:141	arg1	morphogens					143:152	secreted morphogens	134:152	secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms	134:243	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	1	41	theme	secreted	134:141	arg1	proteins					121:128	Wnt proteins	117:128	Wnt proteins	117:128	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	7	42	theme	carbamate	923:931	arg1	ABC99					944:948	ABC99	944:948	ABC99	944:948	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	7	42	theme	carbamate	923:931	arg1	inhibitor					933:941	An optimized NHH carbamate inhibitor	906:941	An optimized NHH carbamate inhibitor	906:941	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	6	43	theme	profiling	773:781	arg1	use					743:745	the use	739:745	the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM	739:903	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	6	44	theme	protein	765:771	arg1	ABPP					784:787	ABPP	784:787	ABPP	784:787	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	6	44	theme	protein	765:771	arg1	profiling					773:781	activity-based protein profiling	750:781	activity-based protein profiling (ABPP)	750:788	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	7	45	theme	optimized	909:917	arg1	ABC99					944:948	ABC99	944:948	ABC99	944:948	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	7	45	theme	optimized	909:917	arg1	inhibitor					933:941	An optimized NHH carbamate inhibitor	906:941	An optimized NHH carbamate inhibitor	906:941	An optimized NHH carbamate inhibitor, ABC99, preserves Wnt-mediated cell signaling in the presence of NOTUM and was also converted into an ABPP probe for visualizing NOTUM in native biological systems.
29937983	3	46	theme	acylation	349:357	arg1	event					359:363	an unusual O-fatty acylation event	330:363	an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors	330:465	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	6	47	theme	activity-based	750:763	arg1	ABPP					784:787	ABPP	784:787	ABPP	784:787	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	6	47	theme	activity-based	750:763	arg1	profiling					773:781	activity-based protein profiling	750:781	activity-based protein profiling (ABPP)	750:788	Here, we describe the use of activity-based protein profiling (ABPP) to discover and advance a class of N-hydroxyhydantoin (NHH) carbamates that potently and selectively inhibit NOTUM.
29937983	3	48	theme	serine	408:413	arg1	palmitoleoylation					375:391	O-linked palmitoleoylation	366:391	O-linked palmitoleoylation of a conserved serine	366:413	Wnts are modified by an unusual O-fatty acylation event (O-linked palmitoleoylation of a conserved serine) that is required for binding to Frizzled receptors.
29937983	1	49	theme	critical	164:171	arg1	roles					173:177	critical roles	164:177	critical roles	164:177	Wnt proteins are secreted morphogens that play critical roles in embryonic development and tissue remodeling in adult organisms.
29937983	5	50	contain	have	670:673	arg2	potential					675:683	potential	675:683	potential	675:683	PORCN inhibitors are under development for oncology, while NOTUM inhibitors have potential for treating degenerative diseases.
29937983	5	50	contain	have	670:673	arg1	inhibitors					659:668	NOTUM inhibitors	653:668	NOTUM inhibitors	653:668	PORCN inhibitors are under development for oncology, while NOTUM inhibitors have potential for treating degenerative diseases.
34532545	2	0	theme	spectrometric	497:509	arg1	analysis					511:518	mass spectrometric analysis	492:518	mass spectrometric analysis	492:518	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	2	0	theme	spectrometric	497:509	arg1	immune-purification					471:489	immune-purification	471:489	immune-purification	471:489	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	2	1	theme	specific	367:374	arg1	protein					376:382	a specific protein	365:382	a specific protein	365:382	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	2	2	theme	mass	492:495	arg1	analysis					511:518	mass spectrometric analysis	492:518	mass spectrometric analysis	492:518	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	2	2	theme	mass	492:495	arg1	immune-purification					471:489	immune-purification	471:489	immune-purification	471:489	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	6	3	theme	conventional	1163:1174	arg1	methods					1176:1182	conventional methods	1163:1182	conventional methods	1163:1182	This new method therefore provides qualitative and quantitative analysis of O-GlcNAcylated proteins in a relatively shorter time compared to conventional methods.
34532545	1	4	theme	Diverse	141:147	arg1	proteins					173:180	Diverse cytoplasmic and nuclear proteins	141:180	Diverse cytoplasmic and nuclear proteins	141:180	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	1	5	theme	O-GlcNAc	262:269	arg1	modification					272:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	230:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues	230:319	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	1	6	dep	serine	288:293	arg1	residues					312:319	residues	312:319	residues	312:319	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	6	7	theme	O-GlcNAcylated	1098:1111	arg1	proteins					1113:1120	O-GlcNAcylated proteins	1098:1120	O-GlcNAcylated proteins	1098:1120	This new method therefore provides qualitative and quantitative analysis of O-GlcNAcylated proteins in a relatively shorter time compared to conventional methods.
34532545	4	8	theme	gel	673:675	arg1	layer					677:681	An O-GlcNAc affinity gel layer	652:681	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA)	652:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	8	theme	gel	673:675	arg1	lectin					741:746	a GlcNAc-specific lectin	723:746	a GlcNAc-specific lectin	723:746	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	2	9	dep	immune-purification	471:489	arg1	e.g.					465:468	e.g.	465:468	e.g.	465:468	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	5	10	theme	proteins	1012:1019	arg1	level					997:1001	the O-GlcNAcylation level	977:1001	the O-GlcNAcylation level of these proteins	977:1019	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	6	11	theme	qualitative	1057:1067	arg1	analysis					1086:1093	qualitative and quantitative analysis	1057:1093	qualitative and quantitative analysis of O-GlcNAcylated proteins	1057:1120	This new method therefore provides qualitative and quantitative analysis of O-GlcNAcylated proteins in a relatively shorter time compared to conventional methods.
34532545	0	12	theme	O-GlcNAc-modified	74:90	arg1	Proteins					92:99	O-GlcNAc-modified Proteins	74:99	O-GlcNAc-modified Proteins	74:99	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	6	13	theme	proteins	1113:1120	arg1	analysis					1086:1093	qualitative and quantitative analysis	1057:1093	qualitative and quantitative analysis of O-GlcNAcylated proteins	1057:1120	This new method therefore provides qualitative and quantitative analysis of O-GlcNAcylated proteins in a relatively shorter time compared to conventional methods.
34532545	5	14	dep	detection	945:953	arg1	the					941:943	the	941:943	the	941:943	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	1	15	theme	cytoplasmic	149:159	arg1	proteins					173:180	Diverse cytoplasmic and nuclear proteins	141:180	Diverse cytoplasmic and nuclear proteins	141:180	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	6	16	theme	new	1027:1029	arg1	method					1031:1036	This new method	1022:1036	This new method	1022:1036	This new method therefore provides qualitative and quantitative analysis of O-GlcNAcylated proteins in a relatively shorter time compared to conventional methods.
34532545	1	17	link	O-linked	230:237	arg1	modification					272:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	230:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues	230:319	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	4	18	theme	affinity	664:671	arg1	layer					677:681	An O-GlcNAc affinity gel layer	652:681	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA)	652:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	18	theme	affinity	664:671	arg1	lectin					741:746	a GlcNAc-specific lectin	723:746	a GlcNAc-specific lectin	723:746	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	0	19	theme	Germ	6:9	arg1	Agglutinin					11:20	Wheat Germ Agglutinin	0:20	Wheat Germ Agglutinin (WGA)	0:26	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	0	19	theme	Germ	6:9	arg1	WGA					23:25	WGA	23:25	WGA	23:25	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	3	20	theme	easy	576:579	arg1	method					591:596	the following easy and rapid method	562:596	the following easy and rapid method for detection of O-GlcNAcylated proteins of interest	562:649	To overcome this drawback, we developed the following easy and rapid method for detection of O-GlcNAcylated proteins of interest.
34532545	1	21	theme	nuclear	165:171	arg1	proteins					173:180	Diverse cytoplasmic and nuclear proteins	141:180	Diverse cytoplasmic and nuclear proteins	141:180	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	0	22	theme	Wheat	0:4	arg1	Agglutinin					11:20	Wheat Germ Agglutinin	0:20	Wheat Germ Agglutinin (WGA)	0:26	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	0	22	theme	Wheat	0:4	arg1	WGA					23:25	WGA	23:25	WGA	23:25	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	4	23	theme	GlcNAc-specific	725:739	arg1	layer					677:681	An O-GlcNAc affinity gel layer	652:681	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA)	652:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	23	theme	GlcNAc-specific	725:739	arg1	lectin					741:746	a GlcNAc-specific lectin	723:746	a GlcNAc-specific lectin	723:746	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	2	24	theme	conventional	443:454	arg1	methods					456:462	conventional methods	443:462	conventional methods (e.g., immune-purification, mass spectrometric analysis)	443:519	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	6	25	theme	shorter	1138:1144	arg1	time					1146:1149	a relatively shorter time	1125:1149	a relatively shorter time compared to conventional methods	1125:1182	This new method therefore provides qualitative and quantitative analysis of O-GlcNAcylated proteins in a relatively shorter time compared to conventional methods.
34532545	5	26	theme	level	997:1001	arg1	quantification					959:972	quantification	959:972	quantification	959:972	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	5	26	theme	level	997:1001	arg1	detection					945:953	detection	945:953	detection	945:953	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	5	27	theme	O-GlcNAcylation	981:995	arg1	level					997:1001	the O-GlcNAcylation level	977:1001	the O-GlcNAcylation level of these proteins	977:1019	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	0	28	theme	Proteins	92:99	arg1	Detection					61:69	the Detection	57:69	the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis	57:138	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	3	29	theme	following	566:574	arg1	method					591:596	the following easy and rapid method	562:596	the following easy and rapid method for detection of O-GlcNAcylated proteins of interest	562:649	To overcome this drawback, we developed the following easy and rapid method for detection of O-GlcNAcylated proteins of interest.
34532545	4	30	theme	germ	700:703	arg1	agglutinin					705:714	wheat germ agglutinin	694:714	wheat germ agglutinin (WGA)	694:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	30	theme	germ	700:703	arg1	WGA					717:719	WGA	717:719	WGA	717:719	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	0	31	theme	Affinity	111:118	arg1	Electrophoresis					124:138	Lectin Affinity Gel Electrophoresis	104:138	Lectin Affinity Gel Electrophoresis	104:138	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	4	32	theme	O-GlcNAc	655:662	arg1	layer					677:681	An O-GlcNAc affinity gel layer	652:681	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA)	652:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	32	theme	O-GlcNAc	655:662	arg1	lectin					741:746	a GlcNAc-specific lectin	723:746	a GlcNAc-specific lectin	723:746	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	2	33	theme	time-consuming	413:426	arg1	steps					428:432	multiple and time-consuming steps	400:432	multiple and time-consuming steps	400:432	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	2	34	theme	multiple	400:407	arg1	steps					428:432	multiple and time-consuming steps	400:432	multiple and time-consuming steps	400:432	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	0	35	theme	Lectin	104:109	arg1	Electrophoresis					124:138	Lectin Affinity Gel Electrophoresis	104:138	Lectin Affinity Gel Electrophoresis	104:138	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	3	36	theme	interest	642:649	arg1	proteins					630:637	O-GlcNAcylated proteins	615:637	O-GlcNAcylated proteins of interest	615:649	To overcome this drawback, we developed the following easy and rapid method for detection of O-GlcNAcylated proteins of interest.
34532545	1	37	theme	molecular	207:215	arg1	functions					217:225	their molecular functions	201:225	their molecular functions	201:225	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	5	38	theme	proteins	922:929	arg1	forms					913:917	O-GlcNAcylated and non-modified forms	881:917	O-GlcNAcylated and non-modified forms of proteins	881:929	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	3	39	theme	rapid	585:589	arg1	method					591:596	the following easy and rapid method	562:596	the following easy and rapid method for detection of O-GlcNAcylated proteins of interest	562:649	To overcome this drawback, we developed the following easy and rapid method for detection of O-GlcNAcylated proteins of interest.
34532545	0	40	theme	Gel	120:122	arg1	Electrophoresis					124:138	Lectin Affinity Gel Electrophoresis	104:138	Lectin Affinity Gel Electrophoresis	104:138	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	2	41	theme	level	356:360	arg1	Evaluation					322:331	Evaluation	322:331	Evaluation of the O-GlcNAcylation level of a specific protein	322:382	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	4	42	theme	O-GlcNAcylated	800:813	arg1	proteins					815:822	O-GlcNAcylated proteins	800:822	O-GlcNAcylated proteins	800:822	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	43	contain	containing	683:692	arg2	WGA					717:719	WGA	717:719	WGA	717:719	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	43	contain	containing	683:692	arg1	layer					677:681	An O-GlcNAc affinity gel layer	652:681	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA)	652:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	43	contain	containing	683:692	arg1	lectin					741:746	a GlcNAc-specific lectin	723:746	a GlcNAc-specific lectin	723:746	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	43	contain	containing	683:692	arg2	agglutinin					705:714	wheat germ agglutinin	694:714	wheat germ agglutinin (WGA)	694:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	3	44	theme	proteins	630:637	arg1	detection					602:610	detection	602:610	detection of O-GlcNAcylated proteins of interest	602:649	To overcome this drawback, we developed the following easy and rapid method for detection of O-GlcNAcylated proteins of interest.
34532545	2	45	theme	O-GlcNAcylation	340:354	arg1	level					356:360	the O-GlcNAcylation level	336:360	the O-GlcNAcylation level of a specific protein	336:382	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	4	46	theme	mobility	788:795	arg1	retardation					769:779	retardation	769:779	retardation of the mobility of O-GlcNAcylated proteins	769:822	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	47	theme	wheat	694:698	arg1	agglutinin					705:714	wheat germ agglutinin	694:714	wheat germ agglutinin (WGA)	694:720	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	4	47	theme	wheat	694:698	arg1	WGA					717:719	WGA	717:719	WGA	717:719	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	6	48	theme	quantitative	1073:1084	arg1	analysis					1086:1093	qualitative and quantitative analysis	1057:1093	qualitative and quantitative analysis of O-GlcNAcylated proteins	1057:1120	This new method therefore provides qualitative and quantitative analysis of O-GlcNAcylated proteins in a relatively shorter time compared to conventional methods.
34532545	0	49	theme	Novel	40:44	arg1	Method					46:51	A Novel Method	38:51	A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis	38:138	Wheat Germ Agglutinin (WGA)-SDS-PAGE: A Novel Method for the Detection of O-GlcNAc-modified Proteins by Lectin Affinity Gel Electrophoresis.
34532545	5	50	theme	O-GlcNAcylated	881:894	arg1	forms					913:917	O-GlcNAcylated and non-modified forms	881:917	O-GlcNAcylated and non-modified forms of proteins	881:929	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	4	51	theme	proteins	815:822	arg1	mobility					788:795	the mobility	784:795	the mobility of O-GlcNAcylated proteins	784:822	An O-GlcNAc affinity gel layer containing wheat germ agglutinin (WGA), a GlcNAc-specific lectin, selectively induces retardation of the mobility of O-GlcNAcylated proteins during electrophoresis.
34532545	1	52	from	modification	272:283	arg1	threonine					302:310	threonine	302:310	threonine	302:310	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	1	52	from	modification	272:283	arg1	serine					288:293	serine	288:293	serine	288:293	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	5	53	theme	non-modified	900:911	arg1	forms					913:917	O-GlcNAcylated and non-modified forms	881:917	O-GlcNAcylated and non-modified forms of proteins	881:929	This WGA-layer thereby separates O-GlcNAcylated and non-modified forms of proteins, allowing the detection and quantification of the O-GlcNAcylation level of these proteins.
34532545	1	54	theme	O-linked	230:237	arg1	modification					272:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	230:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues	230:319	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
34532545	3	55	theme	O-GlcNAcylated	615:628	arg1	proteins					630:637	O-GlcNAcylated proteins	615:637	O-GlcNAcylated proteins of interest	615:649	To overcome this drawback, we developed the following easy and rapid method for detection of O-GlcNAcylated proteins of interest.
34532545	2	56	theme	protein	376:382	arg1	level					356:360	the O-GlcNAcylation level	336:360	the O-GlcNAcylation level of a specific protein	336:382	Evaluation of the O-GlcNAcylation level of a specific protein, however, needs multiple and time-consuming steps if using conventional methods (e.g., immune-purification, mass spectrometric analysis).
34532545	1	57	theme	β-N-acetylglucosamine	239:259	arg1	modification					272:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	230:283	O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues	230:319	Diverse cytoplasmic and nuclear proteins dynamically change their molecular functions by O-linked β-N-acetylglucosamine (O-GlcNAc) modification on serine and/or threonine residues.
31628388	4	0	theme	wild	438:441	arg1	type					443:446	the wild type	434:446	the wild type	434:446	Here we show in a study of the wild type Firmicute Kurthia sp., that curved, functional filaments can adopt a conformation in vivo that is closely related to a uniform, all-L-state.
31628388	1	1	theme	long	139:142	arg1	filaments					153:161	the micrometers long, helical filaments	123:161	filaments	153:161	Bacteria swim and swarm by rotating the micrometers long, helical filaments of their flagella.
31628388	3	2	theme	functional	322:331	arg1	filaments					333:341	all studied functional filaments	310:341	all studied functional filaments	310:341	So far, all studied functional filaments are composed of a mixture of L- and R-state flagellin monomers.
31628388	4	3	from	conformation	517:528	arg1	vivo					533:536	vivo	533:536	vivo	533:536	Here we show in a study of the wild type Firmicute Kurthia sp., that curved, functional filaments can adopt a conformation in vivo that is closely related to a uniform, all-L-state.
31628388	5	4	link	O-linked	796:803	arg1	glycosylation					805:817	O-linked glycosylation	796:817	O-linked glycosylation	796:817	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	5	5	theme	O-linked	796:803	arg1	glycosylation					805:817	O-linked glycosylation	796:817	O-linked glycosylation	796:817	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	1	6	theme	helical	145:151	arg1	filaments					153:161	the micrometers long, helical filaments	123:161	filaments	153:161	Bacteria swim and swarm by rotating the micrometers long, helical filaments of their flagella.
31628388	3	7	theme	studied	314:320	arg1	filaments					333:341	all studied functional filaments	310:341	all studied functional filaments	310:341	So far, all studied functional filaments are composed of a mixture of L- and R-state flagellin monomers.
31628388	0	8	theme	wild-type	4:12	arg1	filament					24:31	The wild-type flagellar filament	0:31	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.	0:85	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.
31628388	2	9	theme	supercoil	291:299	arg1	handedness					262:271	the handedness	258:271	the handedness of the filament's supercoil	258:299	They change direction by reversing their flagellar rotation, which switches the handedness of the filament's supercoil.
31628388	5	10	theme	additional	600:609	arg1	light					611:615	additional light	600:615	additional light	600:615	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	3	11	theme	R-state	379:385	arg1	monomers					397:404	L- and R-state flagellin monomers	372:404	L- and R-state flagellin monomers	372:404	So far, all studied functional filaments are composed of a mixture of L- and R-state flagellin monomers.
31628388	3	12	theme	flagellin	387:395	arg1	monomers					397:404	L- and R-state flagellin monomers	372:404	L- and R-state flagellin monomers	372:404	So far, all studied functional filaments are composed of a mixture of L- and R-state flagellin monomers.
31628388	5	13	theme	flagellar	716:724	arg1	filament					726:733	a wild-type flagellar filament	704:733	a wild-type flagellar filament	704:733	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	1	14	theme	flagella	172:179	arg1	filaments					153:161	the micrometers long, helical filaments	123:161	filaments	153:161	Bacteria swim and swarm by rotating the micrometers long, helical filaments of their flagella.
31628388	0	15	theme	flagellar	14:22	arg1	filament					24:31	The wild-type flagellar filament	0:31	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.	0:85	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.
31628388	3	16	theme	L-	372:373	arg1	monomers					397:404	L- and R-state flagellin monomers	372:404	L- and R-state flagellin monomers	372:404	So far, all studied functional filaments are composed of a mixture of L- and R-state flagellin monomers.
31628388	0	17	from	resolution	67:76	arg1	filament					24:31	The wild-type flagellar filament	0:31	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.	0:85	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.
31628388	5	18	theme	flagellar	639:647	arg1	supercoil					649:657	the flagellar supercoil	635:657	the flagellar supercoil	635:657	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	5	19	theme	glycosylation	805:817	arg1	densities					783:791	clearly densities	775:791	clearly densities of O-linked glycosylation	775:817	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	3	20	theme	monomers	397:404	arg1	mixture					361:367	a mixture	359:367	a mixture of L- and R-state flagellin monomers	359:404	So far, all studied functional filaments are composed of a mixture of L- and R-state flagellin monomers.
31628388	4	21	dep	Kurthia	458:464	arg1	sp.					466:468	Firmicute Kurthia sp.	448:468	Firmicute Kurthia sp.	448:468	Here we show in a study of the wild type Firmicute Kurthia sp., that curved, functional filaments can adopt a conformation in vivo that is closely related to a uniform, all-L-state.
31628388	5	22	theme	wild-type	706:714	arg1	filament					726:733	a wild-type flagellar filament	704:733	a wild-type flagellar filament	704:733	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	0	23	theme	Kurthia	50:56	arg1	filament					24:31	The wild-type flagellar filament	0:31	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.	0:85	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.
31628388	5	24	theme	supercoil	649:657	arg1	transitions					620:630	transitions	620:630	transitions of the flagellar supercoil	620:657	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	5	25	theme	filament	726:733	arg1	structure					691:699	the atomic structure	680:699	the atomic structure of a wild-type flagellar filament	680:733	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	0	26	theme	Firmicute	40:48	arg1	Kurthia					50:56	the Firmicute Kurthia	36:56	the Firmicute Kurthia	36:56	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.
31628388	4	27	theme	curved	476:481	arg1	filaments					495:503	curved, functional filaments	476:503	curved, functional filaments	476:503	Here we show in a study of the wild type Firmicute Kurthia sp., that curved, functional filaments can adopt a conformation in vivo that is closely related to a uniform, all-L-state.
31628388	4	28	dep	curved	476:481	arg1	functional					484:493	functional	484:493	functional	484:493	Here we show in a study of the wild type Firmicute Kurthia sp., that curved, functional filaments can adopt a conformation in vivo that is closely related to a uniform, all-L-state.
31628388	0	29	theme	2.8 Å	61:65	arg1	resolution					67:76	2.8 Å resolution	61:76	2.8 Å resolution in vivo	61:84	The wild-type flagellar filament of the Firmicute Kurthia at 2.8 Å resolution in vivo.
31628388	5	30	theme	atomic	684:689	arg1	structure					691:699	the atomic structure	680:699	the atomic structure of a wild-type flagellar filament	680:733	This sheds additional light on transitions of the flagellar supercoil and uniquely reveals the atomic structure of a wild-type flagellar filament in vivo, including six residues showing clearly densities of O-linked glycosylation.
31628388	4	31	theme	type	443:446	arg1	study					425:429	a study	423:429	a study of the wild type	423:446	Here we show in a study of the wild type Firmicute Kurthia sp., that curved, functional filaments can adopt a conformation in vivo that is closely related to a uniform, all-L-state.
31628388	2	32	theme	flagellar	223:231	arg1	rotation					233:240	their flagellar rotation	217:240	their flagellar rotation	217:240	They change direction by reversing their flagellar rotation, which switches the handedness of the filament's supercoil.
31628388	1	33	theme	micrometers	127:137	arg1	filaments					153:161	the micrometers long, helical filaments	123:161	filaments	153:161	Bacteria swim and swarm by rotating the micrometers long, helical filaments of their flagella.
31189762	6	0	theme	drug	923:926	arg1	systems					937:943	other drug delivery systems	917:943	other drug delivery systems	917:943	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	6	1	theme	tumor	1014:1018	arg1	cells					1020:1024	tumor cells	1014:1024	tumor cells	1014:1024	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	6	2	theme	other	917:921	arg1	systems					937:943	other drug delivery systems	917:943	other drug delivery systems	917:943	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	3	3	theme	cleavable	331:339	arg1	linker					341:346	a cleavable linker	329:346	a cleavable linker satisfying the requirements of both stability and cleavability	329:409	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	5	4	theme	payload	790:796	arg1	SN-38					816:820	SN-38	816:820	SN-38	816:820	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	5	4	theme	payload	790:796	arg1	drug					810:813	a payload anti-cancer drug	788:813	a payload anti-cancer drug	788:813	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	3	5	theme	linker	341:346	arg1	difficult					424:432	difficult	424:432	difficult	424:432	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	3	5	theme	linker	341:346	arg1	development					314:324	The development	310:324	The development of a cleavable linker satisfying the requirements of both stability and cleavability	310:409	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	6	6	from	use	910:912	arg1	systems					937:943	other drug delivery systems	917:943	other drug delivery systems	917:943	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	1	7	theme	Anti-cancer	66:76	arg1	chemotherapy					78:89	Anti-cancer chemotherapy	66:89	Anti-cancer chemotherapy with good efficacy and fewer side effects	66:131	Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable.
31189762	5	8	theme	anti-cancer	798:808	arg1	SN-38					816:820	SN-38	816:820	SN-38	816:820	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	5	8	theme	anti-cancer	798:808	arg1	drug					810:813	a payload anti-cancer drug	788:813	a payload anti-cancer drug	788:813	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	0	9	theme	Stable	2:7	arg1	Spacer					32:37	A Stable and Cleavable O-Linked Spacer	0:37	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems	0:63	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems.
31189762	5	10	theme	B	866:866	arg1	treatment					868:876	cathepsin B treatment	856:876	cathepsin B treatment	856:876	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	6	11	theme	cytotoxic	995:1003	arg1	drugs					1005:1009	cytotoxic drugs	995:1009	cytotoxic drugs	995:1009	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	3	12	theme	stability	384:392	arg1	requirements					363:374	the requirements	359:374	the requirements of both stability and cleavability	359:409	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	6	13	theme	potential	900:908	arg1	use					910:912	potential use	900:912	potential use in other drug delivery systems to lower side effects	900:965	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	0	14	theme	Cleavable	13:21	arg1	Spacer					32:37	A Stable and Cleavable O-Linked Spacer	0:37	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems	0:63	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems.
31189762	3	15	theme	interest	537:544	arg1	drug					529:532	a drug	527:532	a drug of interest	527:544	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	1	16	with	chemotherapy	78:89	arg1	effects					125:131	fewer side effects	114:131	fewer side effects	114:131	Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable.
31189762	1	16	with	chemotherapy	78:89	arg1	efficacy					101:108	good efficacy	96:108	good efficacy	96:108	Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable.
31189762	5	17	theme	corresponding	738:750	arg1	linker					767:772	a corresponding carbonate-type linker	736:772	a corresponding carbonate-type linker	736:772	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	2	18	theme	side	296:299	arg1	effects					301:307	side effects	296:307	side effects	296:307	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	4	19	theme	drug	672:675	arg1	group					661:665	a hydroxy group	651:665	a hydroxy group of a drug	651:675	We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug.
31189762	4	19	theme	drug	672:675	arg1	drug					672:675	a drug	670:675	a drug	670:675	We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug.
31189762	3	20	theme	carbonate	453:461	arg1	moiety					463:468	a carbonate moiety	451:468	a carbonate moiety	451:468	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	5	21	theme	aqueous	708:714	arg1	buffer					724:729	aqueous neutral buffer	708:729	aqueous neutral buffer	708:729	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	4	22	theme	hydroxy	653:659	arg1	group					661:665	a hydroxy group	651:665	a hydroxy group of a drug	651:675	We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug.
31189762	4	22	theme	hydroxy	653:659	arg1	drug					672:675	a drug	670:675	a drug	670:675	We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug.
31189762	2	23	theme	delivery	161:168	arg1	promising					273:281	promising	273:281	promising	273:281	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	2	23	theme	delivery	161:168	arg1	system					170:175	A drug delivery system	154:175	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker	154:268	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	4	24	theme	ester	609:613	arg1	spacers					615:621	ester spacers	609:621	ester spacers	609:621	We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug.
31189762	0	25	theme	O-Linked	23:30	arg1	Spacer					32:37	A Stable and Cleavable O-Linked Spacer	0:37	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems	0:63	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems.
31189762	5	26	theme	neutral	716:722	arg1	buffer					724:729	aqueous neutral buffer	708:729	aqueous neutral buffer	708:729	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	2	27	theme	drug	156:159	arg1	promising					273:281	promising	273:281	promising	273:281	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	2	27	theme	drug	156:159	arg1	system					170:175	A drug delivery system	154:175	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker	154:268	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	2	28	theme	cytotoxic	220:228	arg1	agent					230:234	a cytotoxic agent	218:234	a cytotoxic agent connected with a cleavable linker	218:268	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	5	29	theme	carbonate-type	752:765	arg1	linker					767:772	a corresponding carbonate-type linker	736:772	a corresponding carbonate-type linker	736:772	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	0	30	theme	Drug	43:46	arg1	Systems					57:63	Drug Delivery Systems	43:63	Drug Delivery Systems	43:63	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems.
31189762	6	31	contain	have	895:898	arg2	use					910:912	potential use	900:912	potential use in other drug delivery systems to lower side effects	900:965	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	6	31	contain	have	895:898	arg1	linker					884:889	This linker	879:889	This linker	879:889	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	5	32	theme	two-step	833:840	arg1	sequence					842:849	a two-step sequence	831:849	a two-step sequence	831:849	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	3	33	theme	cleavability	398:409	arg1	requirements					363:374	the requirements	359:374	the requirements of both stability and cleavability	359:409	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	5	34	from	stable	698:703	arg1	buffer					724:729	aqueous neutral buffer	708:729	aqueous neutral buffer	708:729	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	3	35	used	used	473:476	arg2	moiety					463:468	a carbonate moiety	451:468	a carbonate moiety	451:468	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	1	36	theme	fewer	114:118	arg1	effects					125:131	fewer side effects	114:131	fewer side effects	114:131	Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable.
31189762	2	37	theme	cancer-targeting	190:205	arg1	module					207:212	a cancer-targeting module	188:212	a cancer-targeting module	188:212	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	2	38	theme	cleavable	253:261	arg1	linker					263:268	a cleavable linker	251:268	a cleavable linker	251:268	A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects.
31189762	1	39	theme	side	120:123	arg1	effects					125:131	fewer side effects	114:131	fewer side effects	114:131	Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable.
31189762	1	40	theme	good	96:99	arg1	efficacy					101:108	good efficacy	96:108	good efficacy	96:108	Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable.
31189762	4	41	theme	new	566:568	arg1	linker					577:582	a new stable linker	564:582	a new stable linker	564:582	We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug.
31189762	3	42	theme	hydroxy	510:516	arg1	group					518:522	a hydroxy group	508:522	a hydroxy group	508:522	The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest.
31189762	5	43	theme	cathepsin	856:864	arg1	B					866:866	cathepsin B	856:866	cathepsin B treatment	856:876	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	6	44	theme	side	954:957	arg1	effects					959:965	lower side effects	948:965	lower side effects	948:965	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	0	45	theme	Delivery	48:55	arg1	Systems					57:63	Drug Delivery Systems	43:63	Drug Delivery Systems	43:63	A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems.
31189762	5	46	from	buffer	724:729	arg1	stable					698:703	stable	698:703	stable	698:703	This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment.
31189762	6	47	theme	delivery	928:935	arg1	systems					937:943	other drug delivery systems	917:943	other drug delivery systems	917:943	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	6	48	theme	lower	948:952	arg1	effects					959:965	lower side effects	948:965	lower side effects	948:965	This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.
31189762	4	49	theme	stable	570:575	arg1	linker					577:582	a new stable linker	564:582	a new stable linker	564:582	We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug.
30144161	4	0	link	protein-derived	610:624	arg1	motif					645:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	5	1	theme	post-translational	944:961	arg1	modifications					963:975	post-translational modifications	944:975	post-translational modifications	944:975	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	4	2	theme	motif	645:649	arg1	variants					590:597	phosphate variants	580:597	phosphate variants	580:597	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	2	theme	motif	645:649	arg1	model					699:703	a simplified amyloid scaffold model	669:703	a simplified amyloid scaffold model	669:703	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	2	theme	motif	645:649	arg1	glycans					568:574	O-linked glycans	559:574	O-linked glycans	559:574	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	0	3	theme	Peptide	81:87	arg1	Phosphorylation					40:54	Phosphorylation	40:54	Phosphorylation	40:54	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	0	3	theme	Peptide	81:87	arg1	O-GlcNAcylation					20:34	O-GlcNAcylation	20:34	O-GlcNAcylation	20:34	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	0	4	from	Effects	9:15	arg1	Aggregation					92:102	Aggregation	92:102	Aggregation of the Native Peptide	92:124	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	5	5	theme	modifications	963:975	arg1	role					936:939	the role	932:939	the role of post-translational modifications in protein aggregation	932:998	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	4	6	theme	hexapeptide	633:643	arg1	motif					645:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	7	theme	O-linked	559:566	arg1	variants					590:597	phosphate variants	580:597	phosphate variants	580:597	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	7	theme	O-linked	559:566	arg1	model					699:703	a simplified amyloid scaffold model	669:703	a simplified amyloid scaffold model	669:703	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	7	theme	O-linked	559:566	arg1	glycans					568:574	O-linked glycans	559:574	O-linked glycans	559:574	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	8	theme	native	888:893	arg1	peptide					895:901	the native peptide	884:901	the native peptide	884:901	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	5	9	theme	therapeutic	1020:1030	arg1	approach					1032:1039	a novel therapeutic approach	1012:1039	a novel therapeutic approach to protein misfolding diseases	1012:1070	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	5	10	from	role	936:939	arg1	aggregation					988:998	protein aggregation	980:998	protein aggregation	980:998	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	4	11	theme	single	780:785	arg1	glycan					787:792	a single glycan	778:792	a single glycan	778:792	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	0	12	theme	Native	111:116	arg1	Peptide					118:124	the Native Peptide	107:124	the Native Peptide	107:124	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	4	13	theme	scaffold	690:697	arg1	variants					590:597	phosphate variants	580:597	phosphate variants	580:597	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	13	theme	scaffold	690:697	arg1	model					699:703	a simplified amyloid scaffold model	669:703	a simplified amyloid scaffold model	669:703	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	13	theme	scaffold	690:697	arg1	glycans					568:574	O-linked glycans	559:574	O-linked glycans	559:574	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	5	14	theme	protein	1044:1050	arg1	diseases					1063:1070	protein misfolding diseases	1044:1070	protein misfolding diseases	1044:1070	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	1	15	theme	post-translational	201:218	arg1	O-GlcNAcylation					155:169	O-GlcNAcylation	155:169	O-GlcNAcylation	155:169	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	15	theme	post-translational	201:218	arg1	modifications					220:232	very common nucleoplasmic post-translational modifications	175:232	very common nucleoplasmic post-translational modifications	175:232	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	15	theme	post-translational	201:218	arg1	phosphorylation					135:149	Protein phosphorylation	127:149	Protein phosphorylation	127:149	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	16	theme	common	180:185	arg1	O-GlcNAcylation					155:169	O-GlcNAcylation	155:169	O-GlcNAcylation	155:169	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	16	theme	common	180:185	arg1	modifications					220:232	very common nucleoplasmic post-translational modifications	175:232	very common nucleoplasmic post-translational modifications	175:232	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	16	theme	common	180:185	arg1	phosphorylation					135:149	Protein phosphorylation	127:149	Protein phosphorylation	127:149	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	4	17	theme	peptide	895:901	arg1	aggregation					869:879	aggregation	869:879	aggregation of the native peptide	869:901	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	5	18	theme	misfolding	1052:1061	arg1	diseases					1063:1070	protein misfolding diseases	1044:1070	protein misfolding diseases	1044:1070	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	1	19	theme	nucleoplasmic	187:199	arg1	O-GlcNAcylation					155:169	O-GlcNAcylation	155:169	O-GlcNAcylation	155:169	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	19	theme	nucleoplasmic	187:199	arg1	modifications					220:232	very common nucleoplasmic post-translational modifications	175:232	very common nucleoplasmic post-translational modifications	175:232	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	19	theme	nucleoplasmic	187:199	arg1	phosphorylation					135:149	Protein phosphorylation	127:149	Protein phosphorylation	127:149	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	2	20	theme	misfolding	419:428	arg1	diseases					430:437	various protein misfolding diseases	403:437	various protein misfolding diseases	403:437	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	0	21	theme	Distinct	0:7	arg1	Effects					9:15	Distinct Effects	0:15	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide	0:124	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	4	22	theme	tau	606:608	arg1	motif					645:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	2	23	theme	proteins	355:362	arg1	hallmark					391:398	the hallmark	387:398	the hallmark of various protein misfolding diseases	387:437	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	2	23	theme	proteins	355:362	arg1	self-aggregation					321:336	the self-aggregation	317:336	the self-aggregation	317:336	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	2	24	theme	protein	411:417	arg1	diseases					430:437	various protein misfolding diseases	403:437	various protein misfolding diseases	403:437	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	0	25	theme	O-GlcNAcylation	20:34	arg1	Effects					9:15	Distinct Effects	0:15	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide	0:124	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	4	26	link	O-linked	559:566	arg1	variants					590:597	phosphate variants	580:597	phosphate variants	580:597	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	26	link	O-linked	559:566	arg1	model					699:703	a simplified amyloid scaffold model	669:703	a simplified amyloid scaffold model	669:703	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	26	link	O-linked	559:566	arg1	glycans					568:574	O-linked glycans	559:574	O-linked glycans	559:574	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	2	27	theme	amyloidogenic	341:353	arg1	proteins					355:362	amyloidogenic proteins	341:362	amyloidogenic proteins	341:362	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	2	28	dep	phosphate	263:271	arg1	the					259:261	the	259:261	the	259:261	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	4	29	theme	VQIVYK	626:631	arg1	motif					645:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	0	30	theme	Peptide	118:124	arg1	Aggregation					92:102	Aggregation	92:102	Aggregation of the Native Peptide	92:124	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	4	31	theme	phosphate	799:807	arg1	unit					809:812	a phosphate unit	797:812	a phosphate unit	797:812	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	3	32	theme	amyloid	519:525	arg1	scaffold					527:534	a native non-modified amyloid scaffold	497:534	a native non-modified amyloid scaffold	497:534	However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported.
30144161	0	33	theme	Phosphorylation	40:54	arg1	Effects					9:15	Distinct Effects	0:15	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide	0:124	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	4	34	theme	protein-derived	610:624	arg1	motif					645:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	the tau protein-derived VQIVYK hexapeptide motif	602:649	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	3	35	theme	comparable	455:464	arg1	effect					466:471	their comparable effect	449:471	their comparable effect upon co-incubation with a native non-modified amyloid scaffold	449:534	However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported.
30144161	4	36	theme	phosphate	580:588	arg1	variants					590:597	phosphate variants	580:597	phosphate variants	580:597	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	36	theme	phosphate	580:588	arg1	model					699:703	a simplified amyloid scaffold model	669:703	a simplified amyloid scaffold model	669:703	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	36	theme	phosphate	580:588	arg1	glycans					568:574	O-linked glycans	559:574	O-linked glycans	559:574	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	3	37	theme	native	499:504	arg1	scaffold					527:534	a native non-modified amyloid scaffold	497:534	a native non-modified amyloid scaffold	497:534	However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported.
30144161	3	38	with	effect	466:471	arg1	scaffold					527:534	a native non-modified amyloid scaffold	497:534	a native non-modified amyloid scaffold	497:534	However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported.
30144161	4	39	with	co-incubation	820:832	arg1	variant					852:858	the O-GlcNAc variant	839:858	the O-GlcNAc variant	839:858	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	2	40	theme	phosphate	263:271	arg1	Mono-addition					235:247	Mono-addition	235:247	Mono-addition of either the phosphate or the O-GlcNAc group	235:293	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	5	41	theme	protein	980:986	arg1	aggregation					988:998	protein aggregation	980:998	protein aggregation	980:998	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	4	42	theme	O-GlcNAc	843:850	arg1	variant					852:858	the O-GlcNAc variant	839:858	the O-GlcNAc variant	839:858	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	1	43	theme	Protein	127:133	arg1	O-GlcNAcylation					155:169	O-GlcNAcylation	155:169	O-GlcNAcylation	155:169	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	43	theme	Protein	127:133	arg1	phosphorylation					135:149	Protein phosphorylation	127:149	Protein phosphorylation	127:149	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	1	43	theme	Protein	127:133	arg1	modifications					220:232	very common nucleoplasmic post-translational modifications	175:232	very common nucleoplasmic post-translational modifications	175:232	Protein phosphorylation and O-GlcNAcylation are very common nucleoplasmic post-translational modifications.
30144161	5	44	theme	novel	1014:1018	arg1	approach					1032:1039	a novel therapeutic approach	1012:1039	a novel therapeutic approach to protein misfolding diseases	1012:1070	These results shed light on the role of post-translational modifications in protein aggregation and suggest a novel therapeutic approach to protein misfolding diseases.
30144161	2	45	theme	peptides	368:375	arg1	hallmark					391:398	the hallmark	387:398	the hallmark of various protein misfolding diseases	387:437	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	2	45	theme	peptides	368:375	arg1	self-aggregation					321:336	the self-aggregation	317:336	the self-aggregation	317:336	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	0	46	theme	Amyloid	73:79	arg1	Peptide					81:87	a Tau-Derived Amyloid Peptide	59:87	a Tau-Derived Amyloid Peptide	59:87	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	2	47	theme	group	289:293	arg1	Mono-addition					235:247	Mono-addition	235:247	Mono-addition of either the phosphate or the O-GlcNAc group	235:293	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	3	48	theme	non-modified	506:517	arg1	scaffold					527:534	a native non-modified amyloid scaffold	497:534	a native non-modified amyloid scaffold	497:534	However, their comparable effect upon co-incubation with a native non-modified amyloid scaffold has not been reported.
30144161	2	49	theme	various	403:409	arg1	diseases					430:437	various protein misfolding diseases	403:437	various protein misfolding diseases	403:437	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	2	50	theme	diseases	430:437	arg1	hallmark					391:398	the hallmark	387:398	the hallmark of various protein misfolding diseases	387:437	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	2	50	theme	diseases	430:437	arg1	self-aggregation					321:336	the self-aggregation	317:336	the self-aggregation	317:336	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	4	51	theme	amyloid	682:688	arg1	variants					590:597	phosphate variants	580:597	phosphate variants	580:597	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	51	theme	amyloid	682:688	arg1	model					699:703	a simplified amyloid scaffold model	669:703	a simplified amyloid scaffold model	669:703	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	51	theme	amyloid	682:688	arg1	glycans					568:574	O-linked glycans	559:574	O-linked glycans	559:574	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	0	52	theme	Tau-Derived	61:71	arg1	Peptide					81:87	a Tau-Derived Amyloid Peptide	59:87	a Tau-Derived Amyloid Peptide	59:87	Distinct Effects of O-GlcNAcylation and Phosphorylation of a Tau-Derived Amyloid Peptide on Aggregation of the Native Peptide.
30144161	2	53	theme	O-GlcNAc	280:287	arg1	group					289:293	the O-GlcNAc group	276:293	the O-GlcNAc group	276:293	Mono-addition of either the phosphate or the O-GlcNAc group were shown to inhibit the self-aggregation of amyloidogenic proteins and peptides, which is the hallmark of various protein misfolding diseases.
30144161	4	54	theme	simplified	671:680	arg1	variants					590:597	phosphate variants	580:597	phosphate variants	580:597	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	54	theme	simplified	671:680	arg1	model					699:703	a simplified amyloid scaffold model	669:703	a simplified amyloid scaffold model	669:703	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
30144161	4	54	theme	simplified	671:680	arg1	glycans					568:574	O-linked glycans	559:574	O-linked glycans	559:574	O-linked glycans and phosphate variants of the tau protein-derived VQIVYK hexapeptide motif were generated as a simplified amyloid scaffold model and demonstrate that, while self-aggregation can be attenuated by either a single glycan or a phosphate unit, only co-incubation with the O-GlcNAc variant inhibits aggregation of the native peptide.
31417667	2	0	theme	corresponding	323:335	arg1	molecules					337:345	the corresponding molecules	319:345	the corresponding molecules	319:345	In most cases, introducing a spirocyclic center lowered the measured logD 7.4 of the corresponding molecules by as much as -1.0 relative to the more usual heterocycle.
31417667	0	1	theme	Lowering	66:73	arg1	Twist					75:79	a logD Lowering Twist	59:79	a logD Lowering Twist	59:79	Lowering Lipophilicity by Adding Carbon: AzaSpiroHeptanes, a logD Lowering Twist.
31417667	0	1	theme	Lowering	66:73	arg1	AzaSpiroHeptanes					41:56	Carbon: AzaSpiroHeptanes	33:56	Carbon: AzaSpiroHeptanes	33:56	Lowering Lipophilicity by Adding Carbon: AzaSpiroHeptanes, a logD Lowering Twist.
31417667	4	2	theme	N-linked	608:615	arg1	heptane					632:638	N-linked 2-azaspiro[3.3]heptane	608:638	N-linked 2-azaspiro[3.3]heptane	608:638	An exception to this was found with N-linked 2-azaspiro[3.3]heptane, where logD 7.4 increased by as much as +0.5, consistent with the addition of carbon.
31417667	3	3	theme	carbon	500:505	arg1	atom					507:510	a single carbon atom	491:510	a single carbon atom	491:510	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	4	4	with	consistent	686:695	arg1	addition					706:713	the addition	702:713	the addition of carbon	702:723	An exception to this was found with N-linked 2-azaspiro[3.3]heptane, where logD 7.4 increased by as much as +0.5, consistent with the addition of carbon.
31417667	4	5	theme	2-azaspiro[3.3	617:630	arg1	heptane					632:638	N-linked 2-azaspiro[3.3]heptane	608:638	N-linked 2-azaspiro[3.3]heptane	608:638	An exception to this was found with N-linked 2-azaspiro[3.3]heptane, where logD 7.4 increased by as much as +0.5, consistent with the addition of carbon.
31417667	5	6	theme	suitable	817:824	arg1	heptanes					788:795	azaspiro[3.3]heptanes	775:795	azaspiro[3.3]heptanes	775:795	During our investigation, we also concluded that azaspiro[3.3]heptanes are most likely not suitable bioisosteres for morpholines, piperidines, and piperazines, when not used as terminal groups, due to significant changes in their geometry.
31417667	5	6	theme	suitable	817:824	arg1	bioisosteres					826:837	suitable bioisosteres	817:837	suitable bioisosteres for morpholines, piperidines, and piperazines	817:883	During our investigation, we also concluded that azaspiro[3.3]heptanes are most likely not suitable bioisosteres for morpholines, piperidines, and piperazines, when not used as terminal groups, due to significant changes in their geometry.
31417667	3	7	theme	atom	507:510	arg1	change					449:454	the net change	441:454	the net change in the molecule	441:470	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	3	7	theme	atom	507:510	arg1	addition					479:486	the addition	475:486	the addition of a single carbon atom	475:510	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	4	8	link	N-linked	608:615	arg1	heptane					632:638	N-linked 2-azaspiro[3.3]heptane	608:638	N-linked 2-azaspiro[3.3]heptane	608:638	An exception to this was found with N-linked 2-azaspiro[3.3]heptane, where logD 7.4 increased by as much as +0.5, consistent with the addition of carbon.
31417667	3	9	from	change	449:454	arg1	molecule					463:470	the molecule	459:470	the molecule	459:470	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	3	10	theme	single	493:498	arg1	atom					507:510	a single carbon atom	491:510	a single carbon atom	491:510	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	2	11	theme	usual	387:391	arg1	heterocycle					393:403	the more usual heterocycle	378:403	the more usual heterocycle	378:403	In most cases, introducing a spirocyclic center lowered the measured logD 7.4 of the corresponding molecules by as much as -1.0 relative to the more usual heterocycle.
31417667	2	12	theme	spirocyclic	267:277	arg1	center					279:284	a spirocyclic center	265:284	a spirocyclic center	265:284	In most cases, introducing a spirocyclic center lowered the measured logD 7.4 of the corresponding molecules by as much as -1.0 relative to the more usual heterocycle.
31417667	0	13	theme	Carbon	33:38	arg1	Twist					75:79	a logD Lowering Twist	59:79	a logD Lowering Twist	59:79	Lowering Lipophilicity by Adding Carbon: AzaSpiroHeptanes, a logD Lowering Twist.
31417667	0	13	theme	Carbon	33:38	arg1	AzaSpiroHeptanes					41:56	Carbon: AzaSpiroHeptanes	33:56	Carbon: AzaSpiroHeptanes	33:56	Lowering Lipophilicity by Adding Carbon: AzaSpiroHeptanes, a logD Lowering Twist.
31417667	3	14	theme	increased	552:560	arg1	basicity					562:569	increased basicity	552:569	increased basicity	552:569	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	5	15	theme	terminal	903:910	arg1	groups					912:917	terminal groups	903:917	terminal groups	903:917	During our investigation, we also concluded that azaspiro[3.3]heptanes are most likely not suitable bioisosteres for morpholines, piperidines, and piperazines, when not used as terminal groups, due to significant changes in their geometry.
31417667	3	16	theme	basicity	562:569	arg1	terms					543:547	terms	543:547	terms of increased basicity	543:569	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	3	17	theme	net	445:447	arg1	change					449:454	the net change	441:454	the net change in the molecule	441:470	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	3	17	theme	net	445:447	arg1	addition					479:486	the addition	475:486	the addition of a single carbon atom	475:510	This may seem counterintuitive, as the net change in the molecule is the addition of a single carbon atom, but it may be rationalized in terms of increased basicity.
31417667	5	18	theme	due	920:922	arg1	groups					912:917	terminal groups	903:917	terminal groups	903:917	During our investigation, we also concluded that azaspiro[3.3]heptanes are most likely not suitable bioisosteres for morpholines, piperidines, and piperazines, when not used as terminal groups, due to significant changes in their geometry.
31417667	4	19	theme	carbon	718:723	arg1	addition					706:713	the addition	702:713	the addition of carbon	702:723	An exception to this was found with N-linked 2-azaspiro[3.3]heptane, where logD 7.4 increased by as much as +0.5, consistent with the addition of carbon.
31417667	2	20	theme	most	241:244	arg1	cases					246:250	most cases	241:250	most cases	241:250	In most cases, introducing a spirocyclic center lowered the measured logD 7.4 of the corresponding molecules by as much as -1.0 relative to the more usual heterocycle.
31417667	5	21	theme	significant	927:937	arg1	changes					939:945	significant changes	927:945	significant changes in their geometry	927:963	During our investigation, we also concluded that azaspiro[3.3]heptanes are most likely not suitable bioisosteres for morpholines, piperidines, and piperazines, when not used as terminal groups, due to significant changes in their geometry.
31417667	2	22	theme	measured	298:305	arg1	logD					307:310	the measured logD 7.4	294:314	the measured logD 7.4 of the corresponding molecules	294:345	In most cases, introducing a spirocyclic center lowered the measured logD 7.4 of the corresponding molecules by as much as -1.0 relative to the more usual heterocycle.
31417667	0	23	theme	logD	61:64	arg1	Twist					75:79	a logD Lowering Twist	59:79	a logD Lowering Twist	59:79	Lowering Lipophilicity by Adding Carbon: AzaSpiroHeptanes, a logD Lowering Twist.
31417667	0	23	theme	logD	61:64	arg1	AzaSpiroHeptanes					41:56	Carbon: AzaSpiroHeptanes	33:56	Carbon: AzaSpiroHeptanes	33:56	Lowering Lipophilicity by Adding Carbon: AzaSpiroHeptanes, a logD Lowering Twist.
31417667	1	24	theme	heptanes	128:135	arg1	analysis					103:110	an analysis	100:110	an analysis of azaspiro[3.3]heptanes used as replacements for morpholines, piperidines, and piperazines	100:202	We have conducted an analysis of azaspiro[3.3]heptanes used as replacements for morpholines, piperidines, and piperazines in a medicinal chemistry context.
31417667	1	25	theme	medicinal	209:217	arg1	chemistry					219:227	a medicinal chemistry	207:227	a medicinal chemistry context	207:235	We have conducted an analysis of azaspiro[3.3]heptanes used as replacements for morpholines, piperidines, and piperazines in a medicinal chemistry context.
31417667	5	26	from	changes	939:945	arg1	geometry					956:963	their geometry	950:963	their geometry	950:963	During our investigation, we also concluded that azaspiro[3.3]heptanes are most likely not suitable bioisosteres for morpholines, piperidines, and piperazines, when not used as terminal groups, due to significant changes in their geometry.
31417667	2	27	theme	molecules	337:345	arg1	logD					307:310	the measured logD 7.4	294:314	the measured logD 7.4 of the corresponding molecules	294:345	In most cases, introducing a spirocyclic center lowered the measured logD 7.4 of the corresponding molecules by as much as -1.0 relative to the more usual heterocycle.
31417667	1	28	theme	chemistry	219:227	arg1	context					229:235	a medicinal chemistry context	207:235	a medicinal chemistry context	207:235	We have conducted an analysis of azaspiro[3.3]heptanes used as replacements for morpholines, piperidines, and piperazines in a medicinal chemistry context.
29622560	8	0	from	expression	1141:1150	arg1	cells					1182:1186	human aortic smooth muscle cells	1155:1186	human aortic smooth muscle cells	1155:1186	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	12	1	theme	TAA	1755:1757	arg1	formation					1759:1767	TAA formation	1755:1767	TAA formation	1755:1767	Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
29622560	4	2	theme	AngII	538:542	arg1	infusion					561:568	AngII (angiotensin II) infusion	538:568	AngII (angiotensin II) infusion	538:568	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	3	3	theme	TAA	468:470	arg1	development					472:482	TAA development	468:482	TAA development	468:482	This study aimed to investigate the contribution of ADAMTS-5 to TAA development.
29622560	9	4	theme	Adamts5Δcat	1366:1376	arg1	mice					1378:1381	AngII-treated Adamts5Δcat mice	1352:1381	AngII-treated Adamts5Δcat mice	1352:1381	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	6	5	theme	AngII-treated	837:849	arg1	mice					877:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	12	6	theme	ADAMTS	1712:1717	arg1	proteases					1719:1727	the different ADAMTS proteases	1698:1727	the different ADAMTS proteases	1698:1727	Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
29622560	4	7	theme	angiotensin	545:555	arg1	infusion					561:568	AngII (angiotensin II) infusion	538:568	AngII (angiotensin II) infusion	538:568	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	1	8	theme	ECM	233:235	arg1	composition					207:217	composition	207:217	composition	207:217	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	8	theme	ECM	233:235	arg1	structure					193:201	structure	193:201	structure	193:201	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	6	9	theme	ECM	828:830	arg1	comparison					803:812	a proteomic comparison	791:812	a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice	791:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	4	10	theme	catalytic	602:610	arg1	ADAMTS-5					622:629	ADAMTS-5	622:629	ADAMTS-5 (Adamts5Δcat)	622:643	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	4	10	theme	catalytic	602:610	arg1	domain					612:617	the catalytic domain	598:617	the catalytic domain of ADAMTS-5 (Adamts5Δcat)	598:643	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	10	11	theme	ADAMTS	1522:1527	arg1	proteases					1529:1537	ADAMTS proteases	1522:1537	ADAMTS proteases	1522:1537	CONCLUSIONS Our results support the emerging role of ADAMTS proteases in TAA.
29622560	1	12	theme	wall	154:157	arg1	disease					132:138	a degenerative disease	117:138	a degenerative disease of the aortic wall	117:157	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	12	theme	wall	154:157	arg1	aneurysm					101:108	OBJECTIVE Thoracic aortic aneurysm	75:108	OBJECTIVE Thoracic aortic aneurysm (TAA)	75:114	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	8	13	theme	LRP1	1136:1139	arg1	expression					1141:1150	Silencing LRP1 expression	1126:1150	Silencing LRP1 expression in human aortic smooth muscle cells	1126:1186	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	2	14	theme	ADAMTS	265:270	arg1	family					337:342	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family	261:342	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases	261:355	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	6	15	theme	upregulated	912:922	arg1	versican					891:898	versican	891:898	versican	891:898	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	6	15	theme	upregulated	912:922	arg1	protein					928:934	the most upregulated ECM protein	903:934	the most upregulated ECM protein in Adamts5Δcat mice	903:954	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	8	16	theme	ADAMTS5	1214:1220	arg1	expression					1200:1209	the expression	1196:1209	the expression of ADAMTS5	1196:1220	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	6	17	from	comparison	803:812	arg1	mice					877:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	7	18	theme	cleavage	1028:1035	arg1	versikine					1047:1055	versikine	1047:1055	versikine	1047:1055	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	18	theme	cleavage	1028:1035	arg1	products					1037:1044	ADAMTS-specific versican cleavage products	1003:1044	ADAMTS-specific versican cleavage products (versikine)	1003:1056	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	5	19	from	rise	684:687	arg1	pressure					698:705	blood pressure	692:705	blood pressure	692:705	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	9	20	theme	versican	1418:1425	arg1	processing					1427:1436	versican processing	1418:1436	versican processing	1418:1436	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	8	21	theme	aortic	1161:1166	arg1	cells					1182:1186	human aortic smooth muscle cells	1155:1186	human aortic smooth muscle cells	1155:1186	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	7	22	theme	ADAMTS-specific	1003:1017	arg1	versikine					1047:1055	versikine	1047:1055	versikine	1047:1055	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	22	theme	ADAMTS-specific	1003:1017	arg1	products					1037:1044	ADAMTS-specific versican cleavage products	1003:1044	ADAMTS-specific versican cleavage products (versikine)	1003:1056	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	1	23	from	changes	178:184	arg1	composition					207:217	composition	207:217	composition	207:217	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	23	from	changes	178:184	arg1	structure					193:201	structure	193:201	structure	193:201	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	8	24	theme	muscle	1175:1180	arg1	cells					1182:1186	human aortic smooth muscle cells	1155:1186	human aortic smooth muscle cells	1155:1186	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	9	25	theme	aortic	1450:1455	arg1	dilatation					1457:1466	aortic dilatation	1450:1466	aortic dilatation	1450:1466	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	8	26	theme	versikine	1252:1260	arg1	generation					1238:1247	the generation	1234:1247	the generation of versikine	1234:1260	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	12	27	theme	ECM	1680:1682	arg1	substrates					1684:1693	the ECM substrates	1676:1693	the ECM substrates of the different ADAMTS proteases	1676:1727	Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
29622560	9	28	theme	mice	1378:1381	arg1	aortas					1342:1347	aortas	1342:1347	aortas of AngII-treated Adamts5Δcat mice	1342:1381	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	8	29	theme	soluble	1277:1283	arg1	ADAMTS-1					1285:1292	soluble ADAMTS-1	1277:1292	soluble ADAMTS-1	1277:1292	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	6	30	theme	Adamts5Δcat	939:949	arg1	mice					951:954	Adamts5Δcat mice	939:954	Adamts5Δcat mice	939:954	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	0	31	from	Role	0:3	arg1	Dilatation					27:36	Aortic Dilatation	20:36	Aortic Dilatation	20:36	Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.
29622560	0	31	from	Role	0:3	arg1	Remodeling					63:72	Extracellular Matrix Remodeling	42:72	Extracellular Matrix Remodeling	42:72	Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.
29622560	9	32	located	observed	1330:1337	arg1	aortas					1342:1347	aortas	1342:1347	aortas of AngII-treated Adamts5Δcat mice	1342:1381	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	9	32	located	observed	1330:1337	arg2	increase					1305:1312	A similar increase	1295:1312	A similar increase in ADAMTS-1	1295:1324	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	9	32	located	observed	1330:1337	arg2	sufficient					1395:1404	sufficient	1395:1404	sufficient	1395:1404	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	5	33	theme	attenuated	673:682	arg1	rise					684:687	an attenuated rise	670:687	an attenuated rise in blood pressure	670:705	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	5	34	theme	increased	724:732	arg1	dilatation					734:743	increased dilatation	724:743	increased dilatation of the ascending aorta (AsAo)	724:773	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	1	35	theme	OBJECTIVE	75:83	arg1	disease					132:138	a degenerative disease	117:138	a degenerative disease of the aortic wall	117:157	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	35	theme	OBJECTIVE	75:83	arg1	TAA					111:113	TAA	111:113	TAA	111:113	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	35	theme	OBJECTIVE	75:83	arg1	aneurysm					101:108	OBJECTIVE Thoracic aortic aneurysm	75:108	OBJECTIVE Thoracic aortic aneurysm (TAA)	75:114	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	5	36	theme	aorta	762:766	arg1	dilatation					734:743	increased dilatation	724:743	increased dilatation of the ascending aorta (AsAo)	724:773	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	1	37	theme	aortic	94:99	arg1	disease					132:138	a degenerative disease	117:138	a degenerative disease of the aortic wall	117:157	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	37	theme	aortic	94:99	arg1	TAA					111:113	TAA	111:113	TAA	111:113	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	37	theme	aortic	94:99	arg1	aneurysm					101:108	OBJECTIVE Thoracic aortic aneurysm	75:108	OBJECTIVE Thoracic aortic aneurysm (TAA)	75:114	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	0	38	theme	ADAMTS-5	8:15	arg1	Role					0:3	Role	0:3	Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.	0:73	Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.
29622560	2	39	with	disintegrin	275:285	arg1	motifs					329:334	thrombospondin motifs	314:334	thrombospondin motifs	314:334	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	11	40	from	protease	1588:1595	arg1	aortas					1631:1636	murine aortas	1624:1636	murine aortas	1624:1636	ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas.
29622560	4	41	theme	aortic	517:522	arg1	dilatation					524:533	aortic dilatation	517:533	aortic dilatation by AngII (angiotensin II) infusion	517:568	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	7	42	theme	lipoprotein-related	1094:1112	arg1	decrease					1064:1071	a decrease	1062:1071	a decrease of LRP1 (low-density lipoprotein-related protein 1)	1062:1123	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	42	theme	lipoprotein-related	1094:1112	arg1	protein					1114:1120	low-density lipoprotein-related protein 1	1082:1122	low-density lipoprotein-related protein 1	1082:1122	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	0	43	theme	Aortic	20:25	arg1	Dilatation					27:36	Aortic Dilatation	20:36	Aortic Dilatation	20:36	Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.
29622560	6	44	theme	proteomic	793:801	arg1	comparison					803:812	a proteomic comparison	791:812	a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice	791:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	10	45	dep	CONCLUSIONS	1469:1479	arg1	support					1493:1499	support	1493:1499	support the emerging role of ADAMTS proteases in TAA	1493:1544	CONCLUSIONS Our results support the emerging role of ADAMTS proteases in TAA.
29622560	2	46	with	metalloproteinase	291:307	arg1	motifs					329:334	thrombospondin motifs	314:334	thrombospondin motifs	314:334	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	11	47	theme	key	1584:1586	arg1	protease					1588:1595	the key protease	1580:1595	the key protease for versican regulation in murine aortas	1580:1636	ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas.
29622560	11	47	theme	key	1584:1586	arg1	ADAMTS-5					1547:1554	ADAMTS-5	1547:1554	ADAMTS-5 rather than ADAMTS-1	1547:1575	ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas.
29622560	11	47	theme	key	1584:1586	arg1	ADAMTS-1					1568:1575	ADAMTS-1	1568:1575	ADAMTS-5 rather than ADAMTS-1	1547:1575	ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas.
29622560	0	48	theme	Extracellular	42:54	arg1	Remodeling					63:72	Extracellular Matrix Remodeling	42:72	Extracellular Matrix Remodeling	42:72	Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.
29622560	6	49	theme	Adamts5Δcat	865:875	arg1	mice					877:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	10	50	theme	emerging	1505:1512	arg1	role					1514:1517	the emerging role	1501:1517	the emerging role of ADAMTS proteases in TAA	1501:1544	CONCLUSIONS Our results support the emerging role of ADAMTS proteases in TAA.
29622560	2	51	theme	thrombospondin	314:327	arg1	motifs					329:334	thrombospondin motifs	314:334	thrombospondin motifs	314:334	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	9	52	theme	AngII-treated	1352:1364	arg1	mice					1378:1381	AngII-treated Adamts5Δcat mice	1352:1381	AngII-treated Adamts5Δcat mice	1352:1381	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	6	53	theme	wild-type	851:859	arg1	mice					877:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	AngII-treated wild-type and Adamts5Δcat mice	837:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	12	54	theme	proteases	1719:1727	arg1	substrates					1684:1693	the ECM substrates	1676:1693	the ECM substrates of the different ADAMTS proteases	1676:1727	Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
29622560	12	54	theme	proteases	1719:1727	arg1	contribution					1739:1750	their contribution	1733:1750	their contribution to TAA formation	1733:1767	Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
29622560	1	55	theme	aortic	226:231	arg1	matrix					252:257	extracellular matrix	238:257	extracellular matrix	238:257	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	55	theme	aortic	226:231	arg1	ECM					233:235	the aortic ECM	222:235	the aortic ECM (extracellular matrix)	222:258	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	10	56	theme	proteases	1529:1537	arg1	role					1514:1517	the emerging role	1501:1517	the emerging role of ADAMTS proteases in TAA	1501:1544	CONCLUSIONS Our results support the emerging role of ADAMTS proteases in TAA.
29622560	1	57	theme	aortic	147:152	arg1	wall					154:157	the aortic wall	143:157	the aortic wall	143:157	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	6	58	theme	aortic	821:826	arg1	ECM					828:830	the aortic ECM	817:830	the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice	817:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	11	59	theme	murine	1624:1629	arg1	aortas					1631:1636	murine aortas	1624:1636	murine aortas	1624:1636	ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas.
29622560	7	60	theme	products	1037:1044	arg1	reduction					990:998	a marked reduction	981:998	a marked reduction of ADAMTS-specific versican cleavage products (versikine)	981:1056	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	60	theme	products	1037:1044	arg1	decrease					1064:1071	a decrease	1062:1071	a decrease of LRP1 (low-density lipoprotein-related protein 1)	1062:1123	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	60	theme	products	1037:1044	arg1	protein					1114:1120	low-density lipoprotein-related protein 1	1082:1122	low-density lipoprotein-related protein 1	1082:1122	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	8	61	theme	Silencing	1126:1134	arg1	expression					1141:1150	Silencing LRP1 expression	1126:1150	Silencing LRP1 expression in human aortic smooth muscle cells	1126:1186	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	6	62	theme	ECM	924:926	arg1	versican					891:898	versican	891:898	versican	891:898	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	6	62	theme	ECM	924:926	arg1	protein					928:934	the most upregulated ECM protein	903:934	the most upregulated ECM protein in Adamts5Δcat mice	903:954	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	12	63	theme	different	1702:1710	arg1	proteases					1719:1727	the different ADAMTS proteases	1698:1727	the different ADAMTS proteases	1698:1727	Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
29622560	7	64	theme	versican	1019:1026	arg1	versikine					1047:1055	versikine	1047:1055	versikine	1047:1055	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	64	theme	versican	1019:1026	arg1	products					1037:1044	ADAMTS-specific versican cleavage products	1003:1044	ADAMTS-specific versican cleavage products (versikine)	1003:1056	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	8	65	theme	human	1155:1159	arg1	cells					1182:1186	human aortic smooth muscle cells	1155:1186	human aortic smooth muscle cells	1155:1186	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	7	66	theme	marked	983:988	arg1	reduction					990:998	a marked reduction	981:998	a marked reduction of ADAMTS-specific versican cleavage products (versikine)	981:1056	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	8	67	theme	smooth	1168:1173	arg1	cells					1182:1186	human aortic smooth muscle cells	1155:1186	human aortic smooth muscle cells	1155:1186	Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine, but increased soluble ADAMTS-1.
29622560	5	68	theme	blood	692:696	arg1	pressure					698:705	blood pressure	692:705	blood pressure	692:705	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	1	69	theme	degenerative	119:130	arg1	disease					132:138	a degenerative disease	117:138	a degenerative disease of the aortic wall	117:157	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	69	theme	degenerative	119:130	arg1	aneurysm					101:108	OBJECTIVE Thoracic aortic aneurysm	75:108	OBJECTIVE Thoracic aortic aneurysm (TAA)	75:114	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	4	70	theme	ADAMTS-5	622:629	arg1	ADAMTS-5					622:629	ADAMTS-5	622:629	ADAMTS-5 (Adamts5Δcat)	622:643	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	4	70	theme	ADAMTS-5	622:629	arg1	domain					612:617	the catalytic domain	598:617	the catalytic domain of ADAMTS-5 (Adamts5Δcat)	598:643	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	4	71	dep	RESULTS	498:504	arg1	model					508:512	A model	506:512	RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion	498:568	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	12	72	theme	Further	1639:1645	arg1	studies					1647:1653	Further studies	1639:1653	Further studies	1639:1653	Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
29622560	5	73	theme	Adamts5Δcat	646:656	arg1	mice					658:661	Adamts5Δcat mice	646:661	Adamts5Δcat mice	646:661	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	9	74	from	increase	1305:1312	arg1	ADAMTS-1					1317:1324	ADAMTS-1	1317:1324	ADAMTS-1	1317:1324	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	6	75	from	protein	928:934	arg1	mice					951:954	Adamts5Δcat mice	939:954	Adamts5Δcat mice	939:954	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	2	76	theme	proteases	347:355	arg1	family					337:342	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family	261:342	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases	261:355	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	5	77	theme	ascending	752:760	arg1	aorta					762:766	the ascending aorta	748:766	the ascending aorta (AsAo)	748:773	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	5	77	theme	ascending	752:760	arg1	AsAo					769:772	AsAo	769:772	AsAo	769:772	Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo).
29622560	1	78	theme	Thoracic	85:92	arg1	disease					132:138	a degenerative disease	117:138	a degenerative disease of the aortic wall	117:157	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	78	theme	Thoracic	85:92	arg1	TAA					111:113	TAA	111:113	TAA	111:113	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	78	theme	Thoracic	85:92	arg1	aneurysm					101:108	OBJECTIVE Thoracic aortic aneurysm	75:108	OBJECTIVE Thoracic aortic aneurysm (TAA)	75:114	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	79	theme	extracellular	238:250	arg1	matrix					252:257	extracellular matrix	238:257	extracellular matrix	238:257	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	1	79	theme	extracellular	238:250	arg1	ECM					233:235	the aortic ECM	222:235	the aortic ECM (extracellular matrix)	222:258	OBJECTIVE Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix).
29622560	2	80	theme	TAA	389:391	arg1	formation					393:401	TAA formation	389:401	TAA formation	389:401	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	4	81	theme	dilatation	524:533	arg1	model					508:512	A model	506:512	RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion	498:568	APPROACH AND RESULTS A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat).
29622560	7	82	theme	low-density	1082:1092	arg1	decrease					1064:1071	a decrease	1062:1071	a decrease of LRP1 (low-density lipoprotein-related protein 1)	1062:1123	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	82	theme	low-density	1082:1092	arg1	protein					1114:1120	low-density lipoprotein-related protein 1	1082:1122	low-density lipoprotein-related protein 1	1082:1122	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	9	83	theme	similar	1297:1303	arg1	sufficient					1395:1404	sufficient	1395:1404	sufficient	1395:1404	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	9	83	theme	similar	1297:1303	arg1	increase					1305:1312	A similar increase	1295:1312	A similar increase in ADAMTS-1	1295:1324	A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice but was not sufficient to maintain versican processing and prevent aortic dilatation.
29622560	7	84	theme	LRP1	1076:1079	arg1	reduction					990:998	a marked reduction	981:998	a marked reduction of ADAMTS-specific versican cleavage products (versikine)	981:1056	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	84	theme	LRP1	1076:1079	arg1	decrease					1064:1071	a decrease	1062:1071	a decrease of LRP1 (low-density lipoprotein-related protein 1)	1062:1123	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	7	84	theme	LRP1	1076:1079	arg1	protein					1114:1120	low-density lipoprotein-related protein 1	1082:1122	low-density lipoprotein-related protein 1	1082:1122	This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1).
29622560	10	85	from	role	1514:1517	arg1	TAA					1542:1544	TAA	1542:1544	TAA	1542:1544	CONCLUSIONS Our results support the emerging role of ADAMTS proteases in TAA.
29622560	0	86	theme	Matrix	56:61	arg1	Remodeling					63:72	Extracellular Matrix Remodeling	42:72	Extracellular Matrix Remodeling	42:72	Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.
29622560	6	87	from	mice	877:880	arg1	ECM					828:830	the aortic ECM	817:830	the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice	817:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	6	87	from	mice	877:880	arg1	comparison					803:812	a proteomic comparison	791:812	a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice	791:880	Interestingly, a proteomic comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice.
29622560	3	88	theme	ADAMTS-5	456:463	arg1	contribution					440:451	the contribution	436:451	the contribution of ADAMTS-5 to TAA development	436:482	This study aimed to investigate the contribution of ADAMTS-5 to TAA development.
29622560	2	89	dep	family	337:342	arg1	metalloproteinase					291:307	metalloproteinase	291:307	metalloproteinase	291:307	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	2	89	dep	family	337:342	arg1	disintegrin					275:285	a disintegrin	273:285	a disintegrin	273:285	The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation.
29622560	11	90	theme	versican	1601:1608	arg1	regulation					1610:1619	versican regulation	1601:1619	versican regulation	1601:1619	ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas.
31596566	4	0	theme	engineered	661:670	arg1	sequence					676:683	engineered DNA sequence	661:683	engineered DNA sequence	661:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	4	1	theme	sequence	676:683	arg1	kilobases					648:656	100 kilobases	644:656	100 kilobases of engineered DNA sequence	644:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	4	2	theme	cell	550:553	arg1	pools					555:559	23 transgenic cell pools	536:559	23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence	536:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	0	3	from	Engineering	13:23	arg1	Cells					76:80	Chinese Hamster Ovary Cells	54:80	Chinese Hamster Ovary Cells	54:80	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.
31596566	5	4	dep	%	821:821	arg1	to					823:824	to	823:824	to	823:824	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	4	5	theme	DNA	672:674	arg1	sequence					676:683	engineered DNA sequence	661:683	engineered DNA sequence	661:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	6	6	theme	synergistic	977:987	arg1	behavior					989:996	synergistic behavior	977:996	synergistic behavior from genetic perturbations by bridging systems and synthetic biology	977:1065	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	4	7	theme	transgenic	539:548	arg1	pools					555:559	23 transgenic cell pools	536:559	23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence	536:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	6	8	theme	synthetic	1049:1057	arg1	biology					1059:1065	synthetic biology	1049:1065	synthetic biology	1049:1065	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	9	theme	behavior	989:996	arg1	identification					959:972	identification	959:972	identification	959:972	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	9	theme	behavior	989:996	arg1	testing					947:953	rapid hypothesis testing	930:953	rapid hypothesis testing	930:953	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	2	10	theme	biology	289:295	arg1	platform					297:304	a synthetic biology platform	277:304	a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation	277:378	Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation.
31596566	1	11	theme	hamster	91:97	arg1	cells					111:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	5	12	from	heterogeneity	871:883	arg1	IgG					901:903	the secreted IgG	888:903	the secreted IgG	888:903	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	2	13	theme	kinetic	257:263	arg1	models					265:270	systems-level kinetic models	243:270	systems-level kinetic models	243:270	Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation.
31596566	4	14	theme	pools	555:559	arg1	total					527:531	a total	525:531	a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence	525:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	5	15	theme	61.9	826:829	arg1	%					821:821	%	821:821	%	821:821	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	2	16	theme	systems-level	243:255	arg1	models					265:270	systems-level kinetic models	243:270	systems-level kinetic models	243:270	Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation.
31596566	4	17	theme	kilobases	648:656	arg1	total					635:639	a total	633:639	a total of 100 kilobases of engineered DNA sequence	633:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	1	18	theme	protein-based	155:167	arg1	therapeutics					169:180	protein-based therapeutics	155:180	protein-based therapeutics (i.e., "biologics")	155:200	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	5	19	theme	glycans	794:800	arg1	fraction					765:772	the fraction	761:772	the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9%	761:830	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	2	20	link	N-linked	357:364	arg1	glycosylation					366:378	N-linked glycosylation	357:378	N-linked glycosylation	357:378	Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation.
31596566	6	21	theme	genetic	1003:1009	arg1	perturbations					1011:1023	genetic perturbations	1003:1023	genetic perturbations by bridging systems	1003:1043	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	1	22	theme	Chinese	83:89	arg1	cells					111:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	1	23	theme	therapeutics	169:180	arg1	production					141:150	industrial production	130:150	industrial production of protein-based therapeutics (i.e., "biologics")	130:200	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	5	24	theme	five-fold	802:810	arg1	glycans					794:800	bigalactosylated glycans	777:800	bigalactosylated glycans five-fold from 11.9% to 61.9%	777:830	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	1	25	used	used	121:124	arg2	cells					111:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	3	26	theme	galactose	417:425	arg1	incorporation					427:439	galactose incorporation	417:439	galactose incorporation	417:439	Specifically, we sought to increase galactose incorporation on a secreted Immunoglobulin G (IgG) protein.
31596566	0	27	theme	Model-Driven	0:11	arg1	Engineering					13:23	Model-Driven Engineering	0:23	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells	0:80	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.
31596566	2	28	theme	synthetic	279:287	arg1	platform					297:304	a synthetic biology platform	277:304	a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation	277:378	Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation.
31596566	5	29	theme	glycan	864:869	arg1	heterogeneity					871:883	the glycan heterogeneity	860:883	the glycan heterogeneity on the secreted IgG	860:903	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	0	30	theme	N-Linked	28:35	arg1	Glycosylation					37:49	N-Linked Glycosylation	28:49	N-Linked Glycosylation	28:49	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.
31596566	6	31	from	biology	1059:1065	arg1	identification					959:972	identification	959:972	identification	959:972	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	31	from	biology	1059:1065	arg1	behavior					989:996	synergistic behavior	977:996	synergistic behavior from genetic perturbations by bridging systems and synthetic biology	977:1065	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	31	from	biology	1059:1065	arg1	testing					947:953	rapid hypothesis testing	930:953	rapid hypothesis testing	930:953	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	5	32	theme	bigalactosylated	777:792	arg1	glycans					794:800	bigalactosylated glycans	777:800	bigalactosylated glycans five-fold from 11.9% to 61.9%	777:830	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	3	33	theme	G	470:470	arg1	protein					478:484	a secreted Immunoglobulin G (IgG) protein	444:484	a secreted Immunoglobulin G (IgG) protein	444:484	Specifically, we sought to increase galactose incorporation on a secreted Immunoglobulin G (IgG) protein.
31596566	1	34	theme	ovary	99:103	arg1	cells					111:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	6	35	from	perturbations	1011:1023	arg1	identification					959:972	identification	959:972	identification	959:972	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	35	from	perturbations	1011:1023	arg1	behavior					989:996	synergistic behavior	977:996	synergistic behavior from genetic perturbations by bridging systems and synthetic biology	977:1065	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	35	from	perturbations	1011:1023	arg1	testing					947:953	rapid hypothesis testing	930:953	rapid hypothesis testing	930:953	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	36	from	testing	947:953	arg1	biology					1059:1065	synthetic biology	1049:1065	synthetic biology	1049:1065	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	36	from	testing	947:953	arg1	perturbations					1011:1023	genetic perturbations	1003:1023	genetic perturbations by bridging systems	1003:1043	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	1	37	theme	CHO	106:108	arg1	cells					111:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells	83:115	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	4	38	theme	glycoengineering	595:610	arg1	cassettes					612:620	single or three-gene glycoengineering cassettes	574:620	single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence	574:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	5	39	theme	iterative	694:702	arg1	engineering					704:714	iterative engineering	694:714	iterative engineering	694:714	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	3	40	theme	secreted	446:453	arg1	protein					478:484	a secreted Immunoglobulin G (IgG) protein	444:484	a secreted Immunoglobulin G (IgG) protein	444:484	Specifically, we sought to increase galactose incorporation on a secreted Immunoglobulin G (IgG) protein.
31596566	1	41	theme	biologics	190:198	arg1	"					199:199	biologics"	190:199	"biologics"	189:199	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	0	42	theme	Glycosylation	37:49	arg1	Engineering					13:23	Model-Driven Engineering	0:23	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells	0:80	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.
31596566	6	43	theme	hypothesis	936:945	arg1	testing					947:953	rapid hypothesis testing	930:953	rapid hypothesis testing	930:953	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	44	from	identification	959:972	arg1	biology					1059:1065	synthetic biology	1049:1065	synthetic biology	1049:1065	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	6	44	from	identification	959:972	arg1	perturbations					1011:1023	genetic perturbations	1003:1023	genetic perturbations by bridging systems	1003:1043	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	5	45	theme	11.9	817:820	arg1	%					821:821	%	821:821	%	821:821	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	5	46	from	%	830:830	arg1	five-fold					802:810	five-fold	802:810	five-fold	802:810	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	3	47	theme	Immunoglobulin	455:468	arg1	IgG					473:475	IgG	473:475	IgG	473:475	Specifically, we sought to increase galactose incorporation on a secreted Immunoglobulin G (IgG) protein.
31596566	3	47	theme	Immunoglobulin	455:468	arg1	G					470:470	Immunoglobulin G	455:470	a secreted Immunoglobulin G (IgG) protein	444:484	Specifically, we sought to increase galactose incorporation on a secreted Immunoglobulin G (IgG) protein.
31596566	0	48	theme	Hamster	62:68	arg1	Cells					76:80	Chinese Hamster Ovary Cells	54:80	Chinese Hamster Ovary Cells	54:80	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.
31596566	6	49	theme	rapid	930:934	arg1	testing					947:953	rapid hypothesis testing	930:953	rapid hypothesis testing	930:953	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	0	50	theme	Chinese	54:60	arg1	Cells					76:80	Chinese Hamster Ovary Cells	54:80	Chinese Hamster Ovary Cells	54:80	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.
31596566	1	51	dep	therapeutics	169:180	arg1	"					199:199	biologics"	190:199	"biologics"	189:199	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	2	52	theme	multigene	310:318	arg1	overexpression					320:333	multigene overexpression	310:333	multigene overexpression	310:333	Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation.
31596566	5	53	theme	secreted	892:899	arg1	IgG					901:903	the secreted IgG	888:903	the secreted IgG	888:903	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31596566	4	54	theme	single	574:579	arg1	cassettes					612:620	single or three-gene glycoengineering cassettes	574:620	single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence	574:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	1	55	dep	"	199:199	arg1	i.e.					183:186	i.e.	183:186	i.e.	183:186	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	6	56	theme	bridging	1028:1035	arg1	systems					1037:1043	bridging systems	1028:1043	bridging systems	1028:1043	Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
31596566	2	57	theme	N-linked	357:364	arg1	glycosylation					366:378	N-linked glycosylation	357:378	N-linked glycosylation	357:378	Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb N-linked glycosylation.
31596566	4	58	theme	three-gene	584:593	arg1	cassettes					612:620	single or three-gene glycoengineering cassettes	574:620	single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence	574:683	We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence.
31596566	0	59	theme	Ovary	70:74	arg1	Cells					76:80	Chinese Hamster Ovary Cells	54:80	Chinese Hamster Ovary Cells	54:80	Model-Driven Engineering of N-Linked Glycosylation in Chinese Hamster Ovary Cells.
31596566	1	60	theme	industrial	130:139	arg1	production					141:150	industrial production	130:150	industrial production of protein-based therapeutics (i.e., "biologics")	130:200	Chinese hamster ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e., "biologics").
31596566	5	61	theme	model	720:724	arg1	refinement					726:735	model refinement	720:735	model refinement	720:735	Through iterative engineering and model refinement, we rationally increase the fraction of bigalactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG.
31254563	0	0	from	C5	18:19	arg1	salmon					33:38	Atlantic salmon	24:38	Atlantic salmon (Salmo salar)	24:52	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	0	0	from	C5	18:19	arg1	salar					47:51	Salmo salar	41:51	Salmo salar	41:51	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	7	1	from	studies	1035:1041	arg1	function					1061:1068	the complement function	1046:1068	the complement function in fish	1046:1076	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	5	2	theme	acid	786:789	arg1	residues					791:798	acetylated sialic acid residues	768:798	acetylated sialic acid residues	768:798	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	6	3	theme	formalin	901:908	arg1	tissue					922:927	formalin fixed liver tissue	901:927	formalin fixed liver tissue	901:927	Three anti-C5 antisera produced in mice using purified C5 worked in immunohistochemical analyses of formalin fixed liver tissue.
31254563	6	4	theme	anti-C5	807:813	arg1	antisera					815:822	Three anti-C5 antisera	801:822	Three anti-C5 antisera produced in mice using purified C5	801:857	Three anti-C5 antisera produced in mice using purified C5 worked in immunohistochemical analyses of formalin fixed liver tissue.
31254563	3	5	contain	has	444:446	arg1	product					436:442	product	436:442	product	436:442	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	3	5	contain	has	444:446	arg2	weight					460:465	a molecular weight	448:465	a molecular weight of 190 kDa	448:476	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	2	6	from	salmon	282:287	arg1	protein					260:266	protein	260:266	protein	260:266	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	6	from	salmon	282:287	arg1	characterization					228:243	the characterization	224:243	the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture	224:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	6	from	salmon	282:287	arg1	cDNA					251:254	C5 cDNA	248:254	C5 cDNA	248:254	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	3	7	theme	translation	424:434	arg1	product					436:442	product	436:442	product	436:442	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	5	8	theme	sialic	779:784	arg1	residues					791:798	acetylated sialic acid residues	768:798	acetylated sialic acid residues	768:798	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	0	9	theme	cDNA	75:78	arg1	Characterization					55:70	Characterization	55:70	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.	0:106	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	2	10	theme	C5	248:249	arg1	cDNA					251:254	C5 cDNA	248:254	C5 cDNA	248:254	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	4	11	theme	N-linked	642:649	arg1	glycan					673:678	a single N-linked, biantennary, complex glycan	633:678	a single N-linked, biantennary, complex glycan at N1125	633:687	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	7	12	theme	possible	1089:1096	arg1	connection					1098:1107	possible connection	1089:1107	possible connection to stress, disease and glycosylation	1089:1144	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	1	13	theme	Complement	108:117	arg1	factor					152:157	an essential factor	139:157	an essential factor of the defensive complement system in all vertebrates	139:211	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	1	13	theme	Complement	108:117	arg1	component					119:127	Complement component 5	108:129	Complement component 5 (C5)	108:134	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	1	13	theme	Complement	108:117	arg1	C5					132:133	C5	132:133	C5	132:133	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	0	14	theme	protein	81:87	arg1	Characterization					55:70	Characterization	55:70	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.	0:106	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	3	15	theme	long	412:415	arg1	cDNA					369:372	The C5 cDNA	362:372	The C5 cDNA cloned from liver	362:390	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	3	15	theme	long	412:415	arg1	nucleotides					400:410	5079 nucleotides long	395:415	5079 nucleotides long	395:415	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	3	16	theme	C5	366:367	arg1	cDNA					369:372	The C5 cDNA	362:372	The C5 cDNA cloned from liver	362:390	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	3	16	theme	C5	366:367	arg1	nucleotides					400:410	5079 nucleotides long	395:415	5079 nucleotides long	395:415	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	6	17	theme	immunohistochemical	869:887	arg1	analyses					889:896	immunohistochemical analyses	869:896	immunohistochemical analyses of formalin fixed liver tissue	869:927	Three anti-C5 antisera produced in mice using purified C5 worked in immunohistochemical analyses of formalin fixed liver tissue.
31254563	5	18	theme	residues	791:798	arg1	form					760:763	the form	756:763	the form of acetylated sialic acid residues	756:798	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	3	19	theme	molecular	450:458	arg1	weight					460:465	a molecular weight	448:465	a molecular weight of 190 kDa	448:476	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	0	20	theme	factor	11:16	arg1	C5					18:19	Complement factor C5	0:19	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.	0:106	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	6	21	theme	purified	847:854	arg1	C5					856:857	purified C5	847:857	purified C5	847:857	Three anti-C5 antisera produced in mice using purified C5 worked in immunohistochemical analyses of formalin fixed liver tissue.
31254563	4	22	theme	single	635:640	arg1	glycan					673:678	a single N-linked, biantennary, complex glycan	633:678	a single N-linked, biantennary, complex glycan at N1125	633:687	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	2	23	theme	fish	314:317	arg1	species					319:325	a teleost fish species	304:325	a teleost fish species of high importance in aquaculture	304:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	23	theme	fish	314:317	arg1	salmon					282:287	Atlantic salmon	273:287	Atlantic salmon (Salmo salar)	273:301	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	0	24	theme	Complement	0:9	arg1	C5					18:19	Complement factor C5	0:19	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.	0:106	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	2	25	theme	protein	260:266	arg1	characterization					228:243	the characterization	224:243	the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture	224:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	1	26	theme	essential	142:150	arg1	component					119:127	Complement component 5	108:129	Complement component 5 (C5)	108:134	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	1	26	theme	essential	142:150	arg1	factor					152:157	an essential factor	139:157	an essential factor of the defensive complement system in all vertebrates	139:211	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	5	27	theme	N-linked	704:711	arg1	glycan					713:718	the N-linked glycan	700:718	the N-linked glycan	700:718	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	0	28	theme	glycosylation	93:105	arg1	Characterization					55:70	Characterization	55:70	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.	0:106	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	3	29	theme	190 kDa	470:476	arg1	weight					460:465	a molecular weight	448:465	a molecular weight of 190 kDa	448:476	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	7	30	from	function	1061:1068	arg1	fish					1073:1076	fish	1073:1076	fish	1073:1076	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	7	31	theme	complement	1050:1059	arg1	function					1061:1068	the complement function	1046:1068	the complement function in fish	1046:1076	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	7	32	theme	activated	976:984	arg1	forms					992:996	inactive and activated (C5b) forms	963:996	inactive and activated (C5b) forms	963:996	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	7	32	theme	activated	976:984	arg1	C5b					987:989	C5b	987:989	C5b	987:989	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	2	33	theme	cDNA	251:254	arg1	characterization					228:243	the characterization	224:243	the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture	224:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	4	34	dep	N-linked	642:649	arg1	complex					665:671	complex	665:671	complex	665:671	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	4	34	dep	N-linked	642:649	arg1	biantennary					652:662	biantennary	652:662	biantennary	652:662	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	5	35	theme	unusual	732:738	arg1	modification					740:751	an unusual modification	729:751	an unusual modification in the form of acetylated sialic acid residues	729:798	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	2	36	theme	teleost	306:312	arg1	species					319:325	a teleost fish species	304:325	a teleost fish species of high importance in aquaculture	304:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	36	theme	teleost	306:312	arg1	salmon					282:287	Atlantic salmon	273:287	Atlantic salmon (Salmo salar)	273:301	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	37	theme	importance	335:344	arg1	species					319:325	a teleost fish species	304:325	a teleost fish species of high importance in aquaculture	304:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	37	theme	importance	335:344	arg1	salmon					282:287	Atlantic salmon	273:287	Atlantic salmon (Salmo salar)	273:301	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	0	38	theme	Atlantic	24:31	arg1	salmon					33:38	Atlantic salmon	24:38	Atlantic salmon (Salmo salar)	24:52	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	0	38	theme	Atlantic	24:31	arg1	salar					47:51	Salmo salar	41:51	Salmo salar	41:51	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	7	39	theme	inactive	963:970	arg1	forms					992:996	inactive and activated (C5b) forms	963:996	inactive and activated (C5b) forms	963:996	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	7	39	theme	inactive	963:970	arg1	C5b					987:989	C5b	987:989	C5b	987:989	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	1	40	theme	defensive	166:174	arg1	system					187:192	the defensive complement system	162:192	the defensive complement system	162:192	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	0	41	theme	Salmo	41:45	arg1	salmon					33:38	Atlantic salmon	24:38	Atlantic salmon (Salmo salar)	24:52	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	0	41	theme	Salmo	41:45	arg1	salar					47:51	Salmo salar	41:51	Salmo salar	41:51	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	3	42	theme	classical	488:496	arg1	orientation					502:512	the classical β-α orientation	484:512	the classical β-α orientation	484:512	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	5	43	from	modification	740:751	arg1	form					760:763	the form	756:763	the form of acetylated sialic acid residues	756:798	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	2	44	theme	Salmo	290:294	arg1	salmon					282:287	Atlantic salmon	273:287	Atlantic salmon (Salmo salar)	273:301	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	44	theme	Salmo	290:294	arg1	salar					296:300	Salmo salar	290:300	Salmo salar	290:300	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	7	45	theme	interesting	1023:1033	arg1	studies					1035:1041	interesting studies	1023:1041	interesting studies	1023:1041	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	7	45	theme	interesting	1023:1033	arg1	connection					1098:1107	possible connection	1089:1107	possible connection to stress, disease and glycosylation	1089:1144	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	3	46	theme	C5	577:578	arg1	R758					593:596	R758	593:596	R758	593:596	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	3	46	theme	C5	577:578	arg1	convertases					580:590	C5 convertases	577:590	C5 convertases (R758)	577:597	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	3	47	theme	β-α	498:500	arg1	orientation					502:512	the classical β-α orientation	484:512	the classical β-α orientation	484:512	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	1	48	from	factor	152:157	arg1	vertebrates					201:211	all vertebrates	197:211	all vertebrates	197:211	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	4	49	theme	Mass	600:603	arg1	analysis					619:626	Mass spectrometric analysis	600:626	Mass spectrometric analysis	600:626	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	2	50	from	characterization	228:243	arg1	species					319:325	a teleost fish species	304:325	a teleost fish species of high importance in aquaculture	304:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	50	from	characterization	228:243	arg1	salmon					282:287	Atlantic salmon	273:287	Atlantic salmon (Salmo salar)	273:301	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	50	from	characterization	228:243	arg1	salar					296:300	Salmo salar	290:300	Salmo salar	290:300	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	6	51	theme	tissue	922:927	arg1	analyses					889:896	immunohistochemical analyses	869:896	immunohistochemical analyses of formalin fixed liver tissue	869:927	Three anti-C5 antisera produced in mice using purified C5 worked in immunohistochemical analyses of formalin fixed liver tissue.
31254563	4	52	theme	spectrometric	605:617	arg1	analysis					619:626	Mass spectrometric analysis	600:626	Mass spectrometric analysis	600:626	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	5	53	link	N-linked	704:711	arg1	glycan					713:718	the N-linked glycan	700:718	the N-linked glycan	700:718	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	3	54	theme	β-α	535:537	arg1	678RPKR681					549:558	678RPKR681	549:558	678RPKR681	549:558	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	3	54	theme	β-α	535:537	arg1	cleavage					539:546	β-α cleavage	535:546	β-α cleavage (678RPKR681)	535:559	The C5 cDNA cloned from liver is 5079 nucleotides long, whose translation product has a molecular weight of 190 kDa, with the classical β-α orientation and motifs/sites for β-α cleavage (678RPKR681) and cleavage by C5 convertases (R758).
31254563	2	55	from	species	319:325	arg1	aquaculture					349:359	aquaculture	349:359	aquaculture	349:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	4	56	from	N1125	683:687	arg1	glycan					673:678	a single N-linked, biantennary, complex glycan	633:678	a single N-linked, biantennary, complex glycan at N1125	633:687	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	1	57	theme	complement	176:185	arg1	system					187:192	the defensive complement system	162:192	the defensive complement system	162:192	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	7	58	theme	purification	934:945	arg1	method					947:952	The purification method	930:952	The purification method	930:952	The purification method, whereby inactive and activated (C5b) forms were isolated, opens for interesting studies on the complement function in fish, including possible connection to stress, disease and glycosylation.
31254563	0	59	dep	C5	18:19	arg1	Characterization					55:70	Characterization	55:70	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.	0:106	Complement factor C5 in Atlantic salmon (Salmo salar): Characterization of cDNA, protein and glycosylation.
31254563	2	60	from	importance	335:344	arg1	aquaculture					349:359	aquaculture	349:359	aquaculture	349:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	61	theme	Atlantic	273:280	arg1	species					319:325	a teleost fish species	304:325	a teleost fish species of high importance in aquaculture	304:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	61	theme	Atlantic	273:280	arg1	salmon					282:287	Atlantic salmon	273:287	Atlantic salmon (Salmo salar)	273:301	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	61	theme	Atlantic	273:280	arg1	salar					296:300	Salmo salar	290:300	Salmo salar	290:300	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	1	62	theme	system	187:192	arg1	component					119:127	Complement component 5	108:129	Complement component 5 (C5)	108:134	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	1	62	theme	system	187:192	arg1	factor					152:157	an essential factor	139:157	an essential factor of the defensive complement system in all vertebrates	139:211	Complement component 5 (C5) is an essential factor of the defensive complement system in all vertebrates.
31254563	2	63	theme	high	330:333	arg1	importance					335:344	high importance	330:344	high importance in aquaculture	330:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	5	64	theme	acetylated	768:777	arg1	residues					791:798	acetylated sialic acid residues	768:798	acetylated sialic acid residues	768:798	Moreover, the N-linked glycan displays an unusual modification in the form of acetylated sialic acid residues.
31254563	6	65	theme	liver	916:920	arg1	tissue					922:927	formalin fixed liver tissue	901:927	formalin fixed liver tissue	901:927	Three anti-C5 antisera produced in mice using purified C5 worked in immunohistochemical analyses of formalin fixed liver tissue.
31254563	2	66	from	aquaculture	349:359	arg1	species					319:325	a teleost fish species	304:325	a teleost fish species of high importance in aquaculture	304:359	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	2	66	from	aquaculture	349:359	arg1	salmon					282:287	Atlantic salmon	273:287	Atlantic salmon (Salmo salar)	273:301	We report the characterization of C5 cDNA and protein from Atlantic salmon (Salmo salar), a teleost fish species of high importance in aquaculture.
31254563	4	67	link	N-linked	642:649	arg1	glycan					673:678	a single N-linked, biantennary, complex glycan	633:678	a single N-linked, biantennary, complex glycan at N1125	633:687	Mass spectrometric analysis show a single N-linked, biantennary, complex glycan at N1125.
31254563	6	68	theme	fixed	910:914	arg1	tissue					922:927	formalin fixed liver tissue	901:927	formalin fixed liver tissue	901:927	Three anti-C5 antisera produced in mice using purified C5 worked in immunohistochemical analyses of formalin fixed liver tissue.
30706985	5	0	theme	neuraminic	701:710	arg1	acid					712:715	the 9-modified neuraminic acid	686:715	the 9-modified neuraminic acid	686:715	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	6	1	theme	specific	972:979	arg1	sialosides					981:990	specific sialosides	972:990	specific sialosides	972:990	This sydnone sugar presents the possibility of investigating the roles of specific sialosides.
30706985	1	2	theme	unnatural	193:201	arg1	acids					210:214	unnatural sialic acids	193:214	unnatural sialic acids	193:214	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	0	3	theme	Bioorthogonal	105:117	arg1	Reporters					119:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
30706985	4	4	from	positioning	555:565	arg1	sugar					590:594	the sugar	586:594	the sugar	586:594	The positioning of the reporter on the sugar significantly altered its metabolic fate.
30706985	5	5	theme	in	646:647	arg1	assays					665:670	Further in vitro enzymatic assays	638:670	Further in vitro enzymatic assays	638:670	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	1	6	theme	sialic	203:208	arg1	acids					210:214	unnatural sialic acids	193:214	unnatural sialic acids	193:214	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	4	7	theme	metabolic	622:630	arg1	fate					632:635	its metabolic fate	618:635	its metabolic fate	618:635	The positioning of the reporter on the sugar significantly altered its metabolic fate.
30706985	6	8	theme	sydnone	903:909	arg1	sugar					911:915	This sydnone sugar	898:915	This sydnone sugar	898:915	This sydnone sugar presents the possibility of investigating the roles of specific sialosides.
30706985	2	9	theme	global	318:323	arg1	sialylation					325:335	global sialylation	318:335	global sialylation	318:335	However, MOE only reports on global sialylation and dissected information regarding subsets of sialosides is missing.
30706985	3	10	dep	synthesis	429:437	arg1	the					425:427	the	425:427	the	425:427	Described here is the synthesis and utilization of sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates.
30706985	5	11	theme	enzymatic	655:663	arg1	assays					665:670	Further in vitro enzymatic assays	638:670	Further in vitro enzymatic assays	638:670	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	2	12	theme	sialosides	384:393	arg1	subsets					373:379	subsets	373:379	subsets of sialosides	373:393	However, MOE only reports on global sialylation and dissected information regarding subsets of sialosides is missing.
30706985	2	13	dep	MOE	298:300	arg1	dissected					341:349	dissected	341:349	dissected information regarding subsets of sialosides	341:393	However, MOE only reports on global sialylation and dissected information regarding subsets of sialosides is missing.
30706985	2	13	dep	MOE	298:300	arg1	reports					307:313	reports	307:313	only reports on global sialylation	302:335	However, MOE only reports on global sialylation and dissected information regarding subsets of sialosides is missing.
30706985	5	14	theme	linkage-specific	852:867	arg1	sialoproteins					883:895	linkage-specific α2,6-N-linked sialoproteins	852:895	linkage-specific α2,6-N-linked sialoproteins	852:895	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	5	15	theme	favored	809:815	arg1	incorporation					817:829	the favored incorporation	805:829	the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins	805:895	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	6	16	theme	sialosides	981:990	arg1	roles					963:967	the roles	959:967	the roles of specific sialosides	959:990	This sydnone sugar presents the possibility of investigating the roles of specific sialosides.
30706985	5	17	theme	reporter	838:845	arg1	incorporation					817:829	the favored incorporation	805:829	the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins	805:895	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	3	18	theme	acids	465:469	arg1	utilization					443:453	utilization	443:453	utilization	443:453	Described here is the synthesis and utilization of sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates.
30706985	3	18	theme	acids	465:469	arg1	synthesis					429:437	synthesis	429:437	synthesis	429:437	Described here is the synthesis and utilization of sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates.
30706985	0	19	theme	Selective	0:8	arg1	Engineering					10:20	Selective Engineering	0:20	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.	0:128	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
30706985	5	20	theme	9-modified	690:699	arg1	acid					712:715	the 9-modified neuraminic acid	686:715	the 9-modified neuraminic acid	686:715	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	0	21	theme	Linkage-Specific	25:40	arg1	Sialoproteins					56:68	Linkage-Specific α2,6-N-Linked Sialoproteins	25:68	Linkage-Specific α2,6-N-Linked Sialoproteins	25:68	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
30706985	5	22	theme	Further	638:644	arg1	assays					665:670	Further in vitro enzymatic assays	638:670	Further in vitro enzymatic assays	638:670	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	1	23	theme	metabolic	134:142	arg1	MOE					173:175	MOE	173:175	MOE	173:175	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	1	23	theme	metabolic	134:142	arg1	engineering					160:170	metabolic oligosaccharide engineering	134:170	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids	130:214	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	1	24	theme	oligosaccharide	144:158	arg1	MOE					173:175	MOE	173:175	MOE	173:175	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	1	24	theme	oligosaccharide	144:158	arg1	engineering					160:170	metabolic oligosaccharide engineering	134:170	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids	130:214	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	0	25	theme	Sialoproteins	56:68	arg1	Engineering					10:20	Selective Engineering	0:20	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.	0:128	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
30706985	5	26	link	α2,6-N-linked	869:881	arg1	sialoproteins					883:895	linkage-specific α2,6-N-linked sialoproteins	852:895	linkage-specific α2,6-N-linked sialoproteins	852:895	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	3	27	theme	sydnone	487:493	arg1	reporter					495:502	a sydnone reporter	485:502	a sydnone reporter for the metabolic labeling of sialoconjugates	485:548	Described here is the synthesis and utilization of sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates.
30706985	0	28	theme	α2,6-N-Linked	42:54	arg1	Sialoproteins					56:68	Linkage-Specific α2,6-N-Linked Sialoproteins	25:68	Linkage-Specific α2,6-N-Linked Sialoproteins	25:68	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
30706985	4	29	theme	reporter	574:581	arg1	positioning					555:565	The positioning	551:565	The positioning of the reporter on the sugar	551:594	The positioning of the reporter on the sugar significantly altered its metabolic fate.
30706985	3	30	theme	sialic	458:463	arg1	acids					465:469	sialic acids	458:469	sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates	458:548	Described here is the synthesis and utilization of sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates.
30706985	0	31	theme	Sydnone-Modified	76:91	arg1	Reporters					119:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
30706985	1	32	theme	engineering	160:170	arg1	strategy					178:185	The metabolic oligosaccharide engineering (MOE) strategy	130:185	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids	130:214	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	3	33	theme	sialoconjugates	534:548	arg1	labeling					522:529	the metabolic labeling	508:529	the metabolic labeling of sialoconjugates	508:548	Described here is the synthesis and utilization of sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates.
30706985	5	34	theme	α2,6-N-linked	869:881	arg1	sialoproteins					883:895	linkage-specific α2,6-N-linked sialoproteins	852:895	linkage-specific α2,6-N-linked sialoproteins	852:895	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	1	35	from	visualization	241:253	arg1	systems					280:286	living systems	273:286	living systems	273:286	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	3	36	theme	metabolic	512:520	arg1	labeling					522:529	the metabolic labeling	508:529	the metabolic labeling of sialoconjugates	508:548	Described here is the synthesis and utilization of sialic acids modified with a sydnone reporter for the metabolic labeling of sialoconjugates.
30706985	1	37	theme	sialome	262:268	arg1	visualization					241:253	the visualization	237:253	the visualization of the sialome in living systems	237:286	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	5	38	theme	sialyltransferase	751:767	arg1	ST6Gal-I					769:776	the sialyltransferase ST6Gal-I	747:776	the sialyltransferase ST6Gal-I over ST3Gal-IV	747:791	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	5	39	dep	in	646:647	arg1	vitro					649:653	vitro	649:653	vitro	649:653	Further in vitro enzymatic assays revealed that the 9-modified neuraminic acid is preferentially accepted by the sialyltransferase ST6Gal-I over ST3Gal-IV, leading to the favored incorporation of the reporter into linkage-specific α2,6-N-linked sialoproteins.
30706985	0	40	theme	Acid	100:103	arg1	Reporters					119:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
30706985	1	41	theme	living	273:278	arg1	systems					280:286	living systems	273:286	living systems	273:286	The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems.
30706985	0	42	theme	Sialic	93:98	arg1	Reporters					119:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Sydnone-Modified Sialic Acid Bioorthogonal Reporters	76:127	Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters.
31769101	7	0	theme	components	1252:1261	arg1	removal					1232:1238	highly efficient removal	1215:1238	highly efficient removal of cellular components	1215:1261	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	7	1	theme	X-100	1157:1161	arg1	SDS					1165:1167	Triton X-100 & SDS	1150:1167	Triton X-100 & SDS as well as trypsin & Triton X-100	1150:1201	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	3	2	theme	pulmonary	556:564	arg1	dpPHV					580:584	dpPHV	580:584	dpPHV	580:584	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	3	2	theme	pulmonary	556:564	arg1	valves					572:577	decellularized porcine pulmonary heart valves	533:577	decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal	533:636	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	1	3	theme	valve	281:285	arg1	availability					233:244	BACKGROUND Limited availability	214:244	BACKGROUND Limited availability of decellularized allogeneic heart valve	214:285	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
31769101	9	4	theme	inflammation	1646:1657	arg1	degree					1636:1641	the lowest degree	1625:1641	the lowest degree of inflammation of all tested xenogeneic implants	1625:1691	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	0	5	theme	in	199:200	arg1	model					207:211	an ovine in vivo model	190:211	an ovine in vivo model	190:211	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	10	6	theme	immunologic	1762:1772	arg1	load					1774:1777	a low immunologic load	1756:1777	a low immunologic load	1756:1777	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	7	7	theme	decellularization	1120:1136	arg1	procedures					1138:1147	the decellularization procedures	1116:1147	the decellularization procedures	1116:1147	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	7	8	theme	Triton	1190:1195	arg1	X-100					1197:1201	trypsin & Triton X-100	1180:1201	Triton X-100 & SDS as well as trypsin & Triton X-100	1150:1201	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	9	9	theme	xenogeneic	1673:1682	arg1	implants					1684:1691	all tested xenogeneic implants	1662:1691	all tested xenogeneic implants	1662:1691	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	9	10	link	N-linked	1415:1422	arg1	glycans					1424:1430	N-linked glycans	1415:1430	N-linked glycans	1415:1430	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	6	11	from	study	1077:1081	arg1	n = 3					1054:1058	n = 3	1054:1058	n = 3	1054:1058	Allogenic doPHV implantations (n = 3) from a previous study served as control.
31769101	6	11	from	study	1077:1081	arg1	implantations					1039:1051	Allogenic doPHV implantations	1023:1051	Allogenic doPHV implantations (n = 3) from a previous study	1023:1081	Allogenic doPHV implantations (n = 3) from a previous study served as control.
31769101	2	12	theme	xenogeneic	358:367	arg1	valves					369:374	Decellularized xenogeneic valves	343:374	Decellularized xenogeneic valves	343:374	Decellularized xenogeneic valves might constitute an attractive alternative; however, increased immunological hurdles have to be overcome.
31769101	9	13	theme	DNase	1466:1470	arg1	treatment					1474:1482	DNase I treatment	1466:1482	DNase I treatment	1466:1482	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	4	14	theme	decelluarization	681:696	arg1	methods					698:704	nine different decelluarization methods	666:704	nine different decelluarization methods	666:704	METHODS dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content.
31769101	10	15	theme	heart	1727:1731	arg1	valve					1733:1737	Functional xenogeneic heart valve	1705:1737	Functional xenogeneic heart valve	1705:1737	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	0	16	dep	in	199:200	arg1	vivo					202:205	vivo	202:205	vivo	202:205	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	0	17	theme	porcine	145:151	arg1	valves					180:185	porcine xenogeneic pulmonary heart valves	145:185	porcine xenogeneic pulmonary heart valves	145:185	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	5	18	theme	different	870:878	arg1	protocols					898:906	3 different decellularization protocols w/o PNGase F and DNase I treatment	868:941	n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment	856:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	18	theme	different	870:878	arg1	treatment					933:941	DNase I treatment	925:941	DNase I treatment	925:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	18	theme	different	870:878	arg1	PNGase F					912:919	w/o PNGase F	908:919	w/o PNGase F	908:919	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	0	19	theme	pulmonary	164:172	arg1	valves					180:185	porcine xenogeneic pulmonary heart valves	145:185	porcine xenogeneic pulmonary heart valves	145:185	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	10	20	gly	deglycosylation	1867:1881	arg1	dpPHV					1886:1890	dpPHV	1886:1890	dpPHV	1886:1890	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	10	20	gly	deglycosylation	1867:1881	arg1	DNA					1851:1853	DNA	1851:1853	DNA	1851:1853	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	4	21	theme	SDS	770:772	arg1	content					774:780	SDS content	770:780	SDS content	770:780	METHODS dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content.
31769101	0	22	theme	valves	180:185	arg1	performance					130:140	performance	130:140	performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model	130:211	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	10	23	theme	DNA	1851:1853	arg1	deglycosylation					1867:1881	partial deglycosylation	1859:1881	partial deglycosylation of dpPHV	1859:1890	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	10	23	theme	DNA	1851:1853	arg1	removal					1840:1846	enzymatic removal	1830:1846	enzymatic removal of DNA	1830:1853	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	9	24	theme	clinical	1512:1519	arg1	performance					1521:1531	the clinical performance	1508:1531	the clinical performance of Triton X-100 & SDS dpPHV	1508:1559	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	9	25	theme	positive	1488:1495	arg1	effects					1497:1503	positive effects	1488:1503	positive effects	1488:1503	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	8	26	theme	functional	1325:1334	arg1	comparable					1361:1370	comparable	1361:1370	comparable	1361:1370	In vivo, the functional performance of dpPHV was comparable to that of allogeneic controls.
31769101	8	26	theme	functional	1325:1334	arg1	performance					1336:1346	the functional performance	1321:1346	the functional performance of dpPHV	1321:1355	In vivo, the functional performance of dpPHV was comparable to that of allogeneic controls.
31769101	7	27	theme	cellular	1243:1250	arg1	components					1252:1261	cellular components	1243:1261	cellular components	1243:1261	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	5	28	theme	DNase	925:929	arg1	protocols					898:906	3 different decellularization protocols w/o PNGase F and DNase I treatment	868:941	n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment	856:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	28	theme	DNase	925:929	arg1	treatment					933:941	DNase I treatment	925:941	DNase I treatment	925:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	0	29	theme	DNA	83:85	arg1	removal					42:48	enzymatic removal	32:48	enzymatic removal of N-linked glycans and residual DNA	32:85	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	9	30	theme	X-100	1543:1547	arg1	dpPHV					1555:1559	Triton X-100 & SDS dpPHV	1536:1559	Triton X-100 & SDS dpPHV	1536:1559	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	6	31	theme	Allogenic	1023:1031	arg1	n = 3					1054:1058	n = 3	1054:1058	n = 3	1054:1058	Allogenic doPHV implantations (n = 3) from a previous study served as control.
31769101	6	31	theme	Allogenic	1023:1031	arg1	implantations					1039:1051	Allogenic doPHV implantations	1023:1051	Allogenic doPHV implantations (n = 3) from a previous study	1023:1081	Allogenic doPHV implantations (n = 3) from a previous study served as control.
31769101	0	32	theme	inflammatory	95:106	arg1	response					108:115	inflammatory response	95:115	inflammatory response	95:115	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	9	33	theme	SDS	1551:1553	arg1	dpPHV					1555:1559	Triton X-100 & SDS dpPHV	1536:1559	Triton X-100 & SDS dpPHV	1536:1559	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	5	34	theme	ovine	1011:1015	arg1	host					1017:1020	the ovine host	1007:1020	the ovine host	1007:1020	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	10	35	dep	CONCLUSION	1694:1703	arg1	substitutes					1739:1749	substitutes	1739:1749	substitutes with a low immunologic load	1739:1777	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	2	36	theme	immunological	439:451	arg1	hurdles					453:459	increased immunological hurdles	429:459	increased immunological hurdles	429:459	Decellularized xenogeneic valves might constitute an attractive alternative; however, increased immunological hurdles have to be overcome.
31769101	5	37	theme	dpPHV	849:853	arg1	dpPHV					849:853	dpPHV	849:853	dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment)	849:942	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	37	theme	dpPHV	849:853	arg1	groups					839:844	five groups	834:844	five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment)	834:942	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	38	theme	function	968:975	arg1	analysis					956:963	the analysis	952:963	the analysis of function and immunological reaction	952:1002	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	7	39	theme	trypsin	1180:1186	arg1	X-100					1197:1201	trypsin & Triton X-100	1180:1201	Triton X-100 & SDS as well as trypsin & Triton X-100	1150:1201	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	5	40	theme	immunological	981:993	arg1	reaction					995:1002	immunological reaction	981:1002	immunological reaction	981:1002	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	6	41	theme	previous	1068:1075	arg1	study					1077:1081	a previous study	1066:1081	a previous study	1066:1081	Allogenic doPHV implantations (n = 3) from a previous study served as control.
31769101	9	42	theme	enzymatic	1443:1451	arg1	PNGase F					1453:1460	enzymatic PNGase F	1443:1460	enzymatic PNGase F	1443:1460	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	9	43	theme	&	1596:1596	arg1	X-100					1605:1609	trypsin & Triton X-100 dpPHV	1588:1615	trypsin & Triton X-100 dpPHV	1588:1615	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	10	44	theme	partial	1859:1865	arg1	deglycosylation					1867:1881	partial deglycosylation	1859:1881	partial deglycosylation of dpPHV	1859:1890	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	2	45	theme	attractive	396:405	arg1	alternative					407:417	an attractive alternative	393:417	an attractive alternative	393:417	Decellularized xenogeneic valves might constitute an attractive alternative; however, increased immunological hurdles have to be overcome.
31769101	5	46	theme	groups	839:844	arg1	months					824:829	six months	820:829	six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment)	820:942	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	9	47	theme	X-100	1605:1609	arg1	treatment					1575:1583	this treatment	1570:1583	this treatment of trypsin & Triton X-100 dpPHV	1570:1615	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	9	48	dep	had	1484:1486	arg1	whereas					1562:1568	whereas	1562:1568	whereas	1562:1568	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	3	49	from	effect	514:519	arg1	sheep					524:528	sheep	524:528	sheep	524:528	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	3	50	dep	in	506:507	arg1	vivo					509:512	vivo	509:512	vivo	509:512	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	3	51	theme	heart	566:570	arg1	dpPHV					580:584	dpPHV	580:584	dpPHV	580:584	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	3	51	theme	heart	566:570	arg1	valves					572:577	decellularized porcine pulmonary heart valves	533:577	decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal	533:636	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	1	52	theme	decellularized	249:262	arg1	valve					281:285	decellularized allogeneic heart valve	249:285	decellularized allogeneic heart valve	249:285	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
31769101	7	53	theme	&	1163:1163	arg1	SDS					1165:1167	Triton X-100 & SDS	1150:1167	Triton X-100 & SDS as well as trypsin & Triton X-100	1150:1201	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	9	54	theme	lowest	1629:1634	arg1	degree					1636:1641	the lowest degree	1625:1641	the lowest degree of inflammation of all tested xenogeneic implants	1625:1691	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	0	55	from	performance	130:140	arg1	model					207:211	an ovine in vivo model	190:211	an ovine in vivo model	190:211	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	0	56	theme	ovine	193:197	arg1	model					207:211	an ovine in vivo model	190:211	an ovine in vivo model	190:211	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	3	57	theme	porcine	548:554	arg1	dpPHV					580:584	dpPHV	580:584	dpPHV	580:584	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	3	57	theme	porcine	548:554	arg1	valves					572:577	decellularized porcine pulmonary heart valves	533:577	decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal	533:636	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	1	58	theme	heart	275:279	arg1	valve					281:285	decellularized allogeneic heart valve	249:285	decellularized allogeneic heart valve	249:285	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
31769101	5	59	dep	n = 3	856:860	arg1	protocols					898:906	3 different decellularization protocols w/o PNGase F and DNase I treatment	868:941	n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment	856:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	59	dep	n = 3	856:860	arg1	each					862:865	each	862:865	each	862:865	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	59	dep	n = 3	856:860	arg1	treatment					933:941	DNase I treatment	925:941	DNase I treatment	925:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	59	dep	n = 3	856:860	arg1	PNGase F					912:919	w/o PNGase F	908:919	w/o PNGase F	908:919	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	0	60	link	N-linked	53:60	arg1	glycans					62:68	N-linked glycans	53:68	N-linked glycans	53:68	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	9	61	theme	DNA	1436:1438	arg1	Removal					1404:1410	Removal	1404:1410	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment	1404:1482	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	5	62	dep	dpPHV	849:853	arg1	n = 3					856:860	n = 3	856:860	n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment	856:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	10	63	theme	xenogeneic	1716:1725	arg1	valve					1733:1737	Functional xenogeneic heart valve	1705:1737	Functional xenogeneic heart valve	1705:1737	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	10	64	theme	low	1758:1760	arg1	load					1774:1777	a low immunologic load	1756:1777	a low immunologic load	1756:1777	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	5	65	theme	decellularization	880:896	arg1	protocols					898:906	3 different decellularization protocols w/o PNGase F and DNase I treatment	868:941	n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment	856:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	65	theme	decellularization	880:896	arg1	treatment					933:941	DNase I treatment	925:941	DNase I treatment	925:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	65	theme	decellularization	880:896	arg1	PNGase F					912:919	w/o PNGase F	908:919	w/o PNGase F	908:919	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	0	66	theme	N-linked	53:60	arg1	glycans					62:68	N-linked glycans	53:68	N-linked glycans	53:68	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	9	67	theme	tested	1666:1671	arg1	implants					1684:1691	all tested xenogeneic implants	1662:1691	all tested xenogeneic implants	1662:1691	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	5	68	theme	w/o	908:910	arg1	protocols					898:906	3 different decellularization protocols w/o PNGase F and DNase I treatment	868:941	n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment	856:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	68	theme	w/o	908:910	arg1	PNGase F					912:919	w/o PNGase F	908:919	w/o PNGase F	908:919	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	9	69	theme	implants	1684:1691	arg1	degree					1636:1641	the lowest degree	1625:1641	the lowest degree of inflammation of all tested xenogeneic implants	1625:1691	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	2	70	theme	Decellularized	343:356	arg1	valves					369:374	Decellularized xenogeneic valves	343:374	Decellularized xenogeneic valves	343:374	Decellularized xenogeneic valves might constitute an attractive alternative; however, increased immunological hurdles have to be overcome.
31769101	4	71	theme	different	671:679	arg1	methods					698:704	nine different decelluarization methods	666:704	nine different decelluarization methods	666:704	METHODS dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content.
31769101	7	72	dep	RESULTS	1102:1108	arg1	resulted					1203:1210	resulted	1203:1210	resulted	1203:1210	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	10	73	theme	Functional	1705:1714	arg1	valve					1733:1737	Functional xenogeneic heart valve	1705:1737	Functional xenogeneic heart valve	1705:1737	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	0	74	theme	xenogeneic	153:162	arg1	valves					180:185	porcine xenogeneic pulmonary heart valves	145:185	porcine xenogeneic pulmonary heart valves	145:185	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	5	75	from	implantation	794:805	arg1	sheep					810:814	sheep	810:814	sheep	810:814	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	10	76	theme	enzymatic	1830:1838	arg1	removal					1840:1846	enzymatic removal	1830:1846	enzymatic removal of DNA	1830:1853	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	1	77	theme	BACKGROUND	214:223	arg1	availability					233:244	BACKGROUND Limited availability	214:244	BACKGROUND Limited availability of decellularized allogeneic heart valve	214:285	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
31769101	0	78	theme	heart	174:178	arg1	valves					180:185	porcine xenogeneic pulmonary heart valves	145:185	porcine xenogeneic pulmonary heart valves	145:185	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	3	79	theme	DNA	626:628	arg1	removal					630:636	DNA removal	626:636	DNA removal	626:636	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	1	80	dep	substitutes	287:297	arg1	restricts					299:307	restricts	299:307	substitutes restricts the clinical application thereof	287:340	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
31769101	4	81	theme	GAGs	760:763	arg1	respect					728:734	respect	728:734	respect of DNA, hydroxyproline, GAGs, and SDS content	728:780	METHODS dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content.
31769101	9	82	theme	&	1549:1549	arg1	dpPHV					1555:1559	Triton X-100 & SDS dpPHV	1536:1559	Triton X-100 & SDS dpPHV	1536:1559	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	0	83	theme	residual	74:81	arg1	DNA					83:85	residual DNA	74:85	residual DNA	74:85	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	4	84	theme	DNA	739:741	arg1	respect					728:734	respect	728:734	respect of DNA, hydroxyproline, GAGs, and SDS content	728:780	METHODS dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content.
31769101	7	85	theme	efficient	1222:1230	arg1	removal					1232:1238	highly efficient removal	1215:1238	highly efficient removal of cellular components	1215:1261	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	9	86	theme	Triton	1536:1541	arg1	X-100					1543:1547	Triton X-100	1536:1547	Triton X-100 & SDS dpPHV	1536:1559	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	6	87	theme	doPHV	1033:1037	arg1	n = 3					1054:1058	n = 3	1054:1058	n = 3	1054:1058	Allogenic doPHV implantations (n = 3) from a previous study served as control.
31769101	6	87	theme	doPHV	1033:1037	arg1	implantations					1039:1051	Allogenic doPHV implantations	1023:1051	Allogenic doPHV implantations (n = 3) from a previous study	1023:1081	Allogenic doPHV implantations (n = 3) from a previous study served as control.
31769101	4	88	theme	hydroxyproline	744:757	arg1	respect					728:734	respect	728:734	respect of DNA, hydroxyproline, GAGs, and SDS content	728:780	METHODS dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content.
31769101	5	89	theme	reaction	995:1002	arg1	analysis					956:963	the analysis	952:963	the analysis of function and immunological reaction	952:1002	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	8	90	theme	dpPHV	1351:1355	arg1	comparable					1361:1370	comparable	1361:1370	comparable	1361:1370	In vivo, the functional performance of dpPHV was comparable to that of allogeneic controls.
31769101	8	90	theme	dpPHV	1351:1355	arg1	performance					1336:1346	the functional performance	1321:1346	the functional performance of dpPHV	1321:1355	In vivo, the functional performance of dpPHV was comparable to that of allogeneic controls.
31769101	5	91	theme	Orthotopic	783:792	arg1	implantation					794:805	Orthotopic implantation	783:805	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment)	783:942	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	9	92	theme	dpPHV	1555:1559	arg1	performance					1521:1531	the clinical performance	1508:1531	the clinical performance of Triton X-100 & SDS dpPHV	1508:1559	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	9	93	contain	had	1484:1486	arg2	effects					1497:1503	positive effects	1488:1503	positive effects	1488:1503	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	9	93	contain	had	1484:1486	arg1	Removal					1404:1410	Removal	1404:1410	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment	1404:1482	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	7	94	theme	&	1188:1188	arg1	X-100					1197:1201	trypsin & Triton X-100	1180:1201	Triton X-100 & SDS as well as trypsin & Triton X-100	1150:1201	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	4	95	theme	content	774:780	arg1	respect					728:734	respect	728:734	respect of DNA, hydroxyproline, GAGs, and SDS content	728:780	METHODS dpPHV generated by nine different decelluarization methods were characterized in respect of DNA, hydroxyproline, GAGs, and SDS content.
31769101	2	96	theme	increased	429:437	arg1	hurdles					453:459	increased immunological hurdles	429:459	increased immunological hurdles	429:459	Decellularized xenogeneic valves might constitute an attractive alternative; however, increased immunological hurdles have to be overcome.
31769101	0	97	theme	enzymatic	32:40	arg1	removal					42:48	enzymatic removal	32:48	enzymatic removal of N-linked glycans and residual DNA	32:85	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	1	98	theme	clinical	313:320	arg1	application					322:332	the clinical application	309:332	the clinical application	309:332	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
31769101	7	99	theme	Triton	1150:1155	arg1	SDS					1165:1167	Triton X-100 & SDS	1150:1167	Triton X-100 & SDS as well as trypsin & Triton X-100	1150:1201	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	10	100	theme	dpPHV	1886:1890	arg1	deglycosylation					1867:1881	partial deglycosylation	1859:1881	partial deglycosylation of dpPHV	1859:1890	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	10	100	theme	dpPHV	1886:1890	arg1	removal					1840:1846	enzymatic removal	1830:1846	enzymatic removal of DNA	1830:1853	CONCLUSION Functional xenogeneic heart valve substitutes with a low immunologic load can be produced by decellularization combined with enzymatic removal of DNA and partial deglycosylation of dpPHV.
31769101	8	101	theme	allogeneic	1383:1392	arg1	controls					1394:1401	allogeneic controls	1383:1401	allogeneic controls	1383:1401	In vivo, the functional performance of dpPHV was comparable to that of allogeneic controls.
31769101	9	102	theme	trypsin	1588:1594	arg1	X-100					1605:1609	trypsin & Triton X-100 dpPHV	1588:1615	trypsin & Triton X-100 dpPHV	1588:1615	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	9	103	theme	glycans	1424:1430	arg1	Removal					1404:1410	Removal	1404:1410	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment	1404:1482	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	3	104	theme	in	506:507	arg1	effect					514:519	the in vivo effect	502:519	the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal	502:636	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	0	105	theme	glycans	62:68	arg1	removal					42:48	enzymatic removal	32:48	enzymatic removal of N-linked glycans and residual DNA	32:85	Decellularization combined with enzymatic removal of N-linked glycans and residual DNA reduces inflammatory response and improves performance of porcine xenogeneic pulmonary heart valves in an ovine in vivo model.
31769101	9	106	theme	Triton	1598:1603	arg1	X-100					1605:1609	trypsin & Triton X-100 dpPHV	1588:1615	trypsin & Triton X-100 dpPHV	1588:1615	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	5	107	dep	protocols	898:906	arg1	protocols					898:906	3 different decellularization protocols w/o PNGase F and DNase I treatment	868:941	n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment	856:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	107	dep	protocols	898:906	arg1	treatment					933:941	DNase I treatment	925:941	DNase I treatment	925:941	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	5	107	dep	protocols	898:906	arg1	PNGase F					912:919	w/o PNGase F	908:919	w/o PNGase F	908:919	Orthotopic implantation in sheep for six months of five groups of dpPHV (n = 3 each; 3 different decellularization protocols w/o PNGase F and DNase I treatment) allowed the analysis of function and immunological reaction in the ovine host.
31769101	3	108	theme	decellularized	533:546	arg1	dpPHV					580:584	dpPHV	580:584	dpPHV	580:584	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	3	108	theme	decellularized	533:546	arg1	valves					572:577	decellularized porcine pulmonary heart valves	533:577	decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal	533:636	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	7	109	theme	extracellular	1274:1286	arg1	matrix					1288:1293	the extracellular matrix	1270:1293	the extracellular matrix	1270:1293	RESULTS Among the decellularization procedures, Triton X-100 & SDS as well as trypsin & Triton X-100 resulted in highly efficient removal of cellular components, while the extracellular matrix remained intact.
31769101	1	110	theme	Limited	225:231	arg1	availability					233:244	BACKGROUND Limited availability	214:244	BACKGROUND Limited availability of decellularized allogeneic heart valve	214:285	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
31769101	9	111	theme	N-linked	1415:1422	arg1	glycans					1424:1430	N-linked glycans	1415:1430	N-linked glycans	1415:1430	Removal of N-linked glycans and DNA by enzymatic PNGase F and DNase I treatment had positive effects on the clinical performance of Triton X-100 & SDS dpPHV, whereas this treatment of trypsin & Triton X-100 dpPHV induced the lowest degree of inflammation of all tested xenogeneic implants.
31769101	3	112	theme	valves	572:577	arg1	effect					514:519	the in vivo effect	502:519	the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal	502:636	This study aims for the in vivo effect in sheep of decellularized porcine pulmonary heart valves (dpPHV) enzymatically treated for N-glycan and DNA removal.
31769101	1	113	theme	allogeneic	264:273	arg1	valve					281:285	decellularized allogeneic heart valve	249:285	decellularized allogeneic heart valve	249:285	BACKGROUND Limited availability of decellularized allogeneic heart valve substitutes restricts the clinical application thereof.
30796923	5	0	theme	genetic	567:573	arg1	inhibition					575:584	Pharmacologic or genetic inhibition	550:584	Pharmacologic or genetic inhibition of O-GlcNAcylation	550:603	Pharmacologic or genetic inhibition of O-GlcNAcylation led to longer cilia, and vice versa.
30796923	7	1	theme	In vitro	761:768	arg1	assays					780:785	In vitro enzymatic assays	761:785	In vitro enzymatic assays	761:785	In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening.
30796923	3	2	theme	cellular	358:365	arg1	state					377:381	the cellular metabolic state	354:381	the cellular metabolic state	354:381	However, it is almost completely unknown whether the cellular metabolic state affects the assembly of cilia.
30796923	8	3	theme	microtubule	1029:1039	arg1	assembly					1041:1048	the ciliary microtubule assembly	1017:1048	the ciliary microtubule assembly	1017:1048	Taken together, these results uncovered a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly.
30796923	6	4	theme	biochemical	650:660	arg1	assays					662:667	Further biochemical assays	642:667	Further biochemical assays	642:667	Further biochemical assays revealed that both α-tubulin and HDAC6 (histone deacetylase 6) were O-GlcNAcylated in vivo.
30796923	7	5	theme	enzymatic	770:778	arg1	assays					780:785	In vitro enzymatic assays	761:785	In vitro enzymatic assays	761:785	In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening.
30796923	4	6	theme	cilia	536:540	arg1	length					542:547	the cilia length	532:547	the cilia length	532:547	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	8	7	theme	ciliary	1021:1027	arg1	assembly					1041:1048	the ciliary microtubule assembly	1017:1048	the ciliary microtubule assembly	1017:1048	Taken together, these results uncovered a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly.
30796923	6	8	theme	Further	642:648	arg1	assays					662:667	Further biochemical assays	642:667	Further biochemical assays	642:667	Further biochemical assays revealed that both α-tubulin and HDAC6 (histone deacetylase 6) were O-GlcNAcylated in vivo.
30796923	4	9	theme	cellular	502:509	arg1	nutrients					511:519	cellular nutrients	502:519	cellular nutrients	502:519	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	7	10	theme	ciliary	904:910	arg1	shortening					912:921	ciliary shortening	904:921	ciliary shortening	904:921	In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening.
30796923	4	11	link	O-linked	447:454	arg1	O-GlcNAc					479:486	O-GlcNAc	479:486	O-GlcNAc	479:486	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	4	11	link	O-linked	447:454	arg1	β-N-acetylglucosamine					456:476	O-linked β-N-acetylglucosamine	447:476	O-linked β-N-acetylglucosamine (O-GlcNAc)	447:487	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	4	11	link	O-linked	447:454	arg1	sensor					492:497	a sensor	490:497	a sensor of cellular nutrients	490:519	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	9	12	theme	cellular	1133:1140	arg1	response					1142:1149	the cellular response	1129:1149	the cellular response to nutrients	1129:1162	The cross talk between O-GlcNAc and cilium is likely critical for fine-tuning the cellular response to nutrients.
30796923	1	13	theme	sensory	91:97	arg1	cilium					109:114	The sensory organelle cilium	87:114	The sensory organelle cilium	87:114	The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body.
30796923	4	14	theme	nutrients	511:519	arg1	β-N-acetylglucosamine					456:476	O-linked β-N-acetylglucosamine	447:476	O-linked β-N-acetylglucosamine (O-GlcNAc)	447:487	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	4	14	theme	nutrients	511:519	arg1	sensor					492:497	a sensor	490:497	a sensor of cellular nutrients	490:519	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	5	15	theme	longer	612:617	arg1	cilia					619:623	longer cilia	612:623	longer cilia	612:623	Pharmacologic or genetic inhibition of O-GlcNAcylation led to longer cilia, and vice versa.
30796923	1	16	theme	organelle	99:107	arg1	cilium					109:114	The sensory organelle cilium	87:114	The sensory organelle cilium	87:114	The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body.
30796923	7	17	theme	microtubule	851:861	arg1	disassembly					863:873	microtubule disassembly	851:873	microtubule disassembly	851:873	In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening.
30796923	0	18	theme	Ciliary	34:40	arg1	Length					42:47	Primary Ciliary Length	26:47	Primary Ciliary Length	26:47	O-GlcNAcylation Regulates Primary Ciliary Length by Promoting Microtubule Disassembly.
30796923	3	19	theme	cilia	407:411	arg1	assembly					395:402	the assembly	391:402	the assembly of cilia	391:411	However, it is almost completely unknown whether the cellular metabolic state affects the assembly of cilia.
30796923	6	20	theme	histone	709:715	arg1	HDAC6					702:706	HDAC6	702:706	HDAC6 (histone deacetylase 6)	702:730	Further biochemical assays revealed that both α-tubulin and HDAC6 (histone deacetylase 6) were O-GlcNAcylated in vivo.
30796923	6	20	theme	histone	709:715	arg1	deacetylase					717:727	histone deacetylase 6	709:729	histone deacetylase 6	709:729	Further biochemical assays revealed that both α-tubulin and HDAC6 (histone deacetylase 6) were O-GlcNAcylated in vivo.
30796923	1	21	theme	body	211:214	arg1	cells					198:202	all cells	194:202	all cells of our body	194:214	The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body.
30796923	0	22	theme	Primary	26:32	arg1	Length					42:47	Primary Ciliary Length	26:47	Primary Ciliary Length	26:47	O-GlcNAcylation Regulates Primary Ciliary Length by Promoting Microtubule Disassembly.
30796923	7	23	theme	HDAC6	836:840	arg1	O-GlcNAcylation					799:813	O-GlcNAcylation	799:813	O-GlcNAcylation of either tubulin or HDAC6	799:840	In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening.
30796923	8	24	theme	O-GlcNAc	994:1001	arg1	role					986:989	a negative regulatory role	964:989	a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly	964:1048	Taken together, these results uncovered a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly.
30796923	9	25	theme	cross	1055:1059	arg1	critical					1104:1111	critical	1104:1111	critical	1104:1111	The cross talk between O-GlcNAc and cilium is likely critical for fine-tuning the cellular response to nutrients.
30796923	9	25	theme	cross	1055:1059	arg1	talk					1061:1064	The cross talk	1051:1064	The cross talk between O-GlcNAc and cilium	1051:1092	The cross talk between O-GlcNAc and cilium is likely critical for fine-tuning the cellular response to nutrients.
30796923	7	26	theme	tubulin	825:831	arg1	O-GlcNAcylation					799:813	O-GlcNAcylation	799:813	O-GlcNAcylation of either tubulin or HDAC6	799:840	In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening.
30796923	2	27	theme	cellular	256:263	arg1	homeostasis					265:275	cellular homeostasis	256:275	cellular homeostasis	256:275	These ciliary-mediated pathways affect cellular homeostasis and metabolisms profoundly.
30796923	8	28	theme	regulatory	975:984	arg1	role					986:989	a negative regulatory role	964:989	a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly	964:1048	Taken together, these results uncovered a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly.
30796923	0	29	theme	Microtubule	62:72	arg1	Disassembly					74:84	Microtubule Disassembly	62:84	Microtubule Disassembly	62:84	O-GlcNAcylation Regulates Primary Ciliary Length by Promoting Microtubule Disassembly.
30796923	8	30	theme	negative	966:973	arg1	role					986:989	a negative regulatory role	964:989	a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly	964:1048	Taken together, these results uncovered a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly.
30796923	2	31	theme	ciliary-mediated	223:238	arg1	pathways					240:247	These ciliary-mediated pathways	217:247	These ciliary-mediated pathways	217:247	These ciliary-mediated pathways affect cellular homeostasis and metabolisms profoundly.
30796923	5	32	theme	O-GlcNAcylation	589:603	arg1	inhibition					575:584	Pharmacologic or genetic inhibition	550:584	Pharmacologic or genetic inhibition of O-GlcNAcylation	550:603	Pharmacologic or genetic inhibition of O-GlcNAcylation led to longer cilia, and vice versa.
30796923	4	33	theme	O-linked	447:454	arg1	O-GlcNAc					479:486	O-GlcNAc	479:486	O-GlcNAc	479:486	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	4	33	theme	O-linked	447:454	arg1	β-N-acetylglucosamine					456:476	O-linked β-N-acetylglucosamine	447:476	O-linked β-N-acetylglucosamine (O-GlcNAc)	447:487	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	4	33	theme	O-linked	447:454	arg1	sensor					492:497	a sensor	490:497	a sensor of cellular nutrients	490:519	This study is to investigate how O-linked β-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length.
30796923	1	34	theme	transducing	143:153	arg1	cascades					175:182	important signaling cascades	155:182	transducing important signaling cascades	143:182	The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body.
30796923	3	35	theme	metabolic	367:375	arg1	state					377:381	the cellular metabolic state	354:381	the cellular metabolic state	354:381	However, it is almost completely unknown whether the cellular metabolic state affects the assembly of cilia.
30796923	5	36	theme	Pharmacologic	550:562	arg1	inhibition					575:584	Pharmacologic or genetic inhibition	550:584	Pharmacologic or genetic inhibition of O-GlcNAcylation	550:603	Pharmacologic or genetic inhibition of O-GlcNAcylation led to longer cilia, and vice versa.
30796923	1	37	theme	important	155:163	arg1	cascades					175:182	important signaling cascades	155:182	transducing important signaling cascades	143:182	The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body.
30796923	1	38	theme	signaling	165:173	arg1	cascades					175:182	important signaling cascades	155:182	transducing important signaling cascades	143:182	The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body.
31100289	10	0	theme	misuse	1945:1950	arg1	effects					1910:1916	the adverse health effects	1891:1916	the adverse health effects of humidifier disinfectant misuse	1891:1950	We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.
31100289	1	1	theme	Unusual	134:140	arg1	cases					142:146	Unusual cases	134:146	Unusual cases	134:146	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	9	2	theme	metabolic	1730:1738	arg1	problems					1747:1754	metabolic health problems	1730:1754	metabolic health problems	1730:1754	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	1	3	theme	exposure	205:212	arg1	result					195:200	a result	193:200	a result of exposure to chemicals used as humidifier disinfectants	193:258	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	7	4	theme	worms	1333:1337	arg1	cycles					1319:1324	the life cycles	1310:1324	the life cycles of the worms	1310:1337	Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared.
31100289	10	5	theme	disinfectant	1932:1943	arg1	misuse					1945:1950	humidifier disinfectant misuse	1921:1950	humidifier disinfectant misuse	1921:1950	We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.
31100289	10	6	theme	humidifier	1921:1930	arg1	misuse					1945:1950	humidifier disinfectant misuse	1921:1950	humidifier disinfectant misuse	1921:1950	We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.
31100289	6	7	theme	pathway	1052:1058	arg1	analysis					1060:1067	a pathway analysis	1050:1067	a pathway analysis	1050:1067	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	5	8	theme	C.	980:981	arg1	ok1207					997:1002	ok1207	997:1002	ok1207	997:1002	We screened the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants.
31100289	5	8	theme	C.	980:981	arg1	oga-1					991:995	C. elegans oga-1	980:995	C. elegans oga-1(ok1207)	980:1003	We screened the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants.
31100289	0	9	theme	O-GlcNAc	77:84	arg1	transferase					86:96	O-GlcNAc transferase	77:96	the O-GlcNAc transferase pathway in the nematode C. elegans	73:131	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	6	10	dep	C.	1078:1079	arg1	elegans					1081:1087	elegans	1081:1087	elegans	1081:1087	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	5	11	theme	metabolic	955:963	arg1	toxicity					965:972	metabolic toxicity	955:972	metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants	955:1029	We screened the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants.
31100289	4	12	theme	humidifier	733:742	arg1	disinfectants					744:756	the humidifier disinfectants	729:756	the humidifier disinfectants used in the accidents	729:778	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	7	13	from	periods	1299:1305	arg1	cycles					1319:1324	the life cycles	1310:1324	the life cycles of the worms	1310:1337	Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared.
31100289	9	14	theme	N-acetylglucosamine	1579:1597	arg1	transferase					1599:1609	O-linked N-acetylglucosamine transferase	1570:1609	The O-linked N-acetylglucosamine transferase pathway	1566:1617	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	6	15	theme	underlying	1149:1158	arg1	mechanisms					1169:1178	the underlying toxicity mechanisms	1145:1178	the underlying toxicity mechanisms	1145:1178	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	4	16	theme	2-methyl-4-isothiazolin-3-one	681:709	arg1	effect					627:632	the effect	623:632	the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans	623:866	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	4	17	from	effect	627:632	arg1	development					788:798	the development	784:798	the development of metabolic toxicity in the model organism, Caenorhabditis elegans	784:866	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	4	18	theme	model	829:833	arg1	organism					835:842	the model organism	825:842	the model organism	825:842	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	4	18	theme	model	829:833	arg1	elegans					860:866	Caenorhabditis elegans	845:866	Caenorhabditis elegans	845:866	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	7	19	theme	different	1289:1297	arg1	periods					1299:1305	different periods	1289:1305	different periods in the life cycles of the worms	1289:1337	Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared.
31100289	2	20	theme	considerable	333:344	arg1	study					346:350	considerable study	333:350	considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease	333:484	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	0	21	theme	transferase	86:96	arg1	pathway					98:104	the O-GlcNAc transferase pathway	73:104	the O-GlcNAc transferase pathway in the nematode C. elegans	73:131	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	8	22	theme	metabolic	1527:1535	arg1	toxicity					1537:1544	metabolic toxicity	1527:1544	metabolic toxicity	1527:1544	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	1	23	from	2006	302:305	arg1	children					288:295	Korean children	281:295	Korean children from 2006 to 2011	281:313	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	2	24	theme	chemicals	405:413	arg1	toxicity					369:376	the pulmonary toxicity	355:376	the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease	355:484	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	1	25	theme	fatal	151:155	arg1	injury					162:167	fatal lung injury	151:167	fatal lung injury	151:167	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	0	26	theme	life	6:9	arg1	exposure					11:18	Early life exposure	0:18	Early life exposure of a biocide, CMIT/MIT	0:41	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	9	27	theme	early-life	1686:1695	arg1	exposure					1697:1704	early-life exposure	1686:1704	early-life exposure to CMIT/MIT	1686:1716	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	0	28	theme	metabolic	50:58	arg1	toxicity					60:67	metabolic toxicity	50:67	metabolic toxicity	50:67	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	9	29	theme	health	1740:1745	arg1	problems					1747:1754	metabolic health problems	1730:1754	metabolic health problems	1730:1754	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	9	30	link	O-linked	1570:1577	arg1	transferase					1599:1609	O-linked N-acetylglucosamine transferase	1570:1609	The O-linked N-acetylglucosamine transferase pathway	1566:1617	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	1	31	theme	lung	157:160	arg1	injury					162:167	fatal lung injury	151:167	fatal lung injury	151:167	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	0	32	theme	Early	0:4	arg1	exposure					11:18	Early life exposure	0:18	Early life exposure of a biocide, CMIT/MIT	0:41	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	10	33	theme	adverse	1895:1901	arg1	effects					1910:1916	the adverse health effects	1891:1916	the adverse health effects of humidifier disinfectant misuse	1891:1950	We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.
31100289	3	34	theme	health	536:541	arg1	effects					543:549	health effects	536:549	health effects other than lung disease	536:573	However, the systemic toxicity of the former and health effects other than lung disease are not fully understood.
31100289	1	35	theme	injury	162:167	arg1	cases					142:146	Unusual cases	134:146	Unusual cases	134:146	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	2	36	theme	disinfectant	392:403	arg1	chemicals					405:413	humidifier disinfectant chemicals	381:413	humidifier disinfectant chemicals	381:413	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	1	37	theme	humidifier	235:244	arg1	disinfectants					246:258	humidifier disinfectants	235:258	humidifier disinfectants	235:258	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	6	38	theme	library	1115:1121	arg1	screening					1123:1131	C. elegans transcription factor RNAi library screening	1078:1131	C. elegans transcription factor RNAi library screening	1078:1131	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	9	39	theme	transferase	1599:1609	arg1	pathway					1611:1617	The O-linked N-acetylglucosamine transferase pathway	1566:1617	The O-linked N-acetylglucosamine transferase pathway	1566:1617	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	2	40	theme	humidifier	381:390	arg1	chemicals					405:413	humidifier disinfectant chemicals	381:413	humidifier disinfectant chemicals	381:413	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	5	41	theme	CMIT/MIT	936:943	arg1	potential					923:931	the potential	919:931	the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants	919:1029	We screened the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants.
31100289	8	42	theme	N-acetylglucosamine	1431:1449	arg1	transferase					1451:1461	O-linked N-acetylglucosamine transferase	1422:1461	O-linked N-acetylglucosamine transferase	1422:1461	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	3	43	theme	former	525:530	arg1	toxicity					509:516	the systemic toxicity	496:516	the systemic toxicity of the former	496:530	However, the systemic toxicity of the former and health effects other than lung disease are not fully understood.
31100289	3	43	theme	former	525:530	arg1	effects					543:549	health effects	536:549	health effects other than lung disease	536:573	However, the systemic toxicity of the former and health effects other than lung disease are not fully understood.
31100289	3	43	theme	former	525:530	arg1	disease					567:573	lung disease	562:573	health effects other than lung disease	536:573	However, the systemic toxicity of the former and health effects other than lung disease are not fully understood.
31100289	2	44	theme	toxicity	369:376	arg1	study					346:350	considerable study	333:350	considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease	333:484	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	0	45	theme	biocide	25:31	arg1	CMIT/MIT					34:41	a biocide, CMIT/MIT	23:41	CMIT/MIT	34:41	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	6	46	theme	transcription	1089:1101	arg1	screening					1123:1131	C. elegans transcription factor RNAi library screening	1078:1131	C. elegans transcription factor RNAi library screening	1078:1131	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	0	47	theme	C.	122:123	arg1	elegans					125:131	the nematode C. elegans	109:131	the nematode C. elegans	109:131	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	7	48	theme	exposure	1227:1234	arg1	window					1217:1222	the critical window	1204:1222	the critical window of exposure for metabolic toxicity	1204:1257	Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared.
31100289	4	49	theme	metabolic	803:811	arg1	toxicity					813:820	metabolic toxicity	803:820	metabolic toxicity	803:820	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	8	50	link	O-linked	1422:1429	arg1	transferase					1451:1461	O-linked N-acetylglucosamine transferase	1422:1461	O-linked N-acetylglucosamine transferase	1422:1461	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	2	51	theme	pulmonary	359:367	arg1	toxicity					369:376	the pulmonary toxicity	355:376	the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease	355:484	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	2	52	theme	causal	432:437	arg1	relationship					439:450	the causal relationship	428:450	the causal relationship between exposure and lung disease	428:484	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	0	53	theme	nematode	113:120	arg1	elegans					125:131	the nematode C. elegans	109:131	the nematode C. elegans	109:131	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	3	54	theme	lung	562:565	arg1	disease					567:573	lung disease	562:573	health effects other than lung disease	536:573	However, the systemic toxicity of the former and health effects other than lung disease are not fully understood.
31100289	5	55	dep	oga-1	991:995	arg1	mutants					1023:1029	mutants	1023:1029	mutants	1023:1029	We screened the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants.
31100289	0	56	theme	CMIT/MIT	34:41	arg1	exposure					11:18	Early life exposure	0:18	Early life exposure of a biocide, CMIT/MIT	0:41	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	4	57	theme	scenario	886:893	arg1	comparison					895:904	an exposure scenario comparison	874:904	an exposure scenario comparison	874:904	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	6	58	theme	factor	1103:1108	arg1	screening					1123:1131	C. elegans transcription factor RNAi library screening	1078:1131	C. elegans transcription factor RNAi library screening	1078:1131	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	8	59	theme	critical	1494:1501	arg1	life					1473:1476	early life	1467:1476	early life	1467:1476	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	8	59	theme	critical	1494:1501	arg1	window					1503:1508	the critical window	1490:1508	the critical window for exposure for metabolic toxicity for this substance	1490:1563	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	4	60	theme	exposure	877:884	arg1	comparison					895:904	an exposure scenario comparison	874:904	an exposure scenario comparison	874:904	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	0	61	from	pathway	98:104	arg1	elegans					125:131	the nematode C. elegans	109:131	the nematode C. elegans	109:131	Early life exposure of a biocide, CMIT/MIT causes metabolic toxicity via the O-GlcNAc transferase pathway in the nematode C. elegans.
31100289	4	62	theme	toxicity	813:820	arg1	development					788:798	the development	784:798	the development of metabolic toxicity in the model organism, Caenorhabditis elegans	784:866	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	7	63	theme	life	1314:1317	arg1	cycles					1319:1324	the life cycles	1310:1324	the life cycles of the worms	1310:1337	Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared.
31100289	5	64	dep	C.	980:981	arg1	elegans					983:989	elegans	983:989	elegans	983:989	We screened the potential of CMIT/MIT to induce metabolic toxicity using C. elegans oga-1(ok1207) and ogt-1(ok1474) mutants.
31100289	8	65	theme	O-linked	1422:1429	arg1	transferase					1451:1461	O-linked N-acetylglucosamine transferase	1422:1461	O-linked N-acetylglucosamine transferase	1422:1461	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	1	66	theme	Korean	281:286	arg1	children					288:295	Korean children	281:295	Korean children from 2006 to 2011	281:313	Unusual cases of fatal lung injury, later determined to be a result of exposure to chemicals used as humidifier disinfectants, were reported among Korean children from 2006 to 2011.
31100289	9	67	theme	adult	1763:1767	arg1	life					1769:1772	adult life	1763:1772	adult life in humans	1763:1782	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	8	68	theme	early	1467:1471	arg1	life					1473:1476	early life	1467:1476	early life	1467:1476	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	8	68	theme	early	1467:1471	arg1	window					1503:1508	the critical window	1490:1508	the critical window for exposure for metabolic toxicity for this substance	1490:1563	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	8	69	theme	metabolic	1395:1403	arg1	toxicity					1405:1412	metabolic toxicity	1395:1412	metabolic toxicity	1395:1412	We determined that CMIT/MIT could induce metabolic toxicity through O-linked N-acetylglucosamine transferase and early life seems to be the critical window for exposure for metabolic toxicity for this substance.
31100289	10	70	theme	systemic	1813:1820	arg1	approach					1831:1838	a systemic toxicity approach	1811:1838	a systemic toxicity approach	1811:1838	We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.
31100289	7	71	theme	metabolic	1240:1248	arg1	toxicity					1250:1257	metabolic toxicity	1240:1257	metabolic toxicity	1240:1257	Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared.
31100289	9	72	theme	O-linked	1570:1577	arg1	transferase					1599:1609	O-linked N-acetylglucosamine transferase	1570:1609	The O-linked N-acetylglucosamine transferase pathway	1566:1617	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	3	73	theme	systemic	500:507	arg1	toxicity					509:516	the systemic toxicity	496:516	the systemic toxicity of the former	496:530	However, the systemic toxicity of the former and health effects other than lung disease are not fully understood.
31100289	10	74	theme	health	1903:1908	arg1	effects					1910:1916	the adverse health effects	1891:1916	the adverse health effects of humidifier disinfectant misuse	1891:1950	We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.
31100289	6	75	theme	toxicity	1160:1167	arg1	mechanisms					1169:1178	the underlying toxicity mechanisms	1145:1178	the underlying toxicity mechanisms	1145:1178	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	4	76	from	development	788:798	arg1	organism					835:842	the model organism	825:842	the model organism	825:842	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	4	76	from	development	788:798	arg1	elegans					860:866	Caenorhabditis elegans	845:866	Caenorhabditis elegans	845:866	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	6	77	theme	C.	1078:1079	arg1	screening					1123:1131	C. elegans transcription factor RNAi library screening	1078:1131	C. elegans transcription factor RNAi library screening	1078:1131	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	2	78	theme	lung	473:476	arg1	disease					478:484	lung disease	473:484	lung disease	473:484	This resulted in considerable study of the pulmonary toxicity of humidifier disinfectant chemicals to establish the causal relationship between exposure and lung disease.
31100289	9	79	from	life	1769:1772	arg1	humans					1777:1782	humans	1777:1782	humans	1777:1782	The O-linked N-acetylglucosamine transferase pathway is conserved from worms to humans; our results thus insinuate that early-life exposure to CMIT/MIT could cause metabolic health problems during adult life in humans.
31100289	4	80	theme	5-chloro-2-methyl-4-isothiazoline-3-one	637:675	arg1	effect					627:632	the effect	623:632	the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans	623:866	Here, we investigated the effect of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), among the humidifier disinfectants used in the accidents, on the development of metabolic toxicity in the model organism, Caenorhabditis elegans using an exposure scenario comparison.
31100289	3	81	dep	other	551:555	arg1	than					557:560	than	557:560	than	557:560	However, the systemic toxicity of the former and health effects other than lung disease are not fully understood.
31100289	7	82	theme	critical	1208:1215	arg1	window					1217:1222	the critical window	1204:1222	the critical window of exposure for metabolic toxicity	1204:1257	Finally, to understand the critical window of exposure for metabolic toxicity, responses to exposure during different periods in the life cycles of the worms were compared.
31100289	6	83	theme	RNAi	1110:1113	arg1	screening					1123:1131	C. elegans transcription factor RNAi library screening	1078:1131	C. elegans transcription factor RNAi library screening	1078:1131	We also performed a pathway analysis based on C. elegans transcription factor RNAi library screening to identify the underlying toxicity mechanisms.
31100289	10	84	theme	toxicity	1822:1829	arg1	approach					1831:1838	a systemic toxicity approach	1811:1838	a systemic toxicity approach	1811:1838	We therefore suggest that a systemic toxicity approach should be considered to comprehensively understand the adverse health effects of humidifier disinfectant misuse.
30853938	7	0	from	experiments	881:891	arg1	cells					909:913	human cancer cells	896:913	human cancer cells	896:913	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	5	1	theme	D1	647:648	arg1	stability					627:635	the stability	623:635	the stability of cyclin D1	623:648	High O-GlcNAc levels increase the stability of cyclin D1, while reduction of O-GlcNAcylation strongly decreases it.
30853938	7	2	theme	human	896:900	arg1	cells					909:913	human cancer cells	896:913	human cancer cells	896:913	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	4	3	theme	D1	579:580	arg1	half-life					582:590	cyclin D1 half-life	572:590	cyclin D1 half-life	572:590	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	5	4	theme	High	593:596	arg1	levels					607:612	High O-GlcNAc levels	593:612	High O-GlcNAc levels	593:612	High O-GlcNAc levels increase the stability of cyclin D1, while reduction of O-GlcNAcylation strongly decreases it.
30853938	7	5	theme	imaging	873:879	arg1	experiments					881:891	biochemical and cell imaging experiments	852:891	experiments	881:891	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	4	6	theme	cyclin	572:577	arg1	D1					579:580	cyclin D1	572:580	cyclin D1 half-life	572:590	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	4	7	theme	dynamic	478:484	arg1	β-N-Acetyl-glucosaminylation					510:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation	474:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation)	474:555	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	4	7	theme	dynamic	478:484	arg1	O-GlcNAcylation					540:554	O-GlcNAcylation	540:554	O-GlcNAcylation	540:554	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	5	8	theme	O-GlcNAc	598:605	arg1	levels					607:612	High O-GlcNAc levels	593:612	High O-GlcNAc levels	593:612	High O-GlcNAc levels increase the stability of cyclin D1, while reduction of O-GlcNAcylation strongly decreases it.
30853938	1	9	dep	kinases	121:127	arg1	kinases					121:127	cyclin-dependent kinases	104:127	the cyclin-dependent kinases (CDKs) CDK4 or CDK6	100:147	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	9	dep	kinases	121:127	arg1	CDK6					144:147	CDK6	144:147	CDK6	144:147	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	9	dep	kinases	121:127	arg1	CDK4					136:139	CDK4	136:139	CDK4	136:139	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	3	10	theme	accurate	326:333	arg1	activation					335:344	their timely and accurate activation	309:344	their timely and accurate activation	309:344	To ensure their timely and accurate activation during cell cycle progression, cyclin D1 turnover is finely controlled by phosphorylation and ubiquitination.
30853938	1	11	theme	Cyclin	61:66	arg1	D1					68:69	Cyclin D1	61:69	Cyclin D1	61:69	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	11	theme	Cyclin	61:66	arg1	partner					89:95	the regulatory partner	74:95	the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6	74:147	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	2	12	theme	phase	243:247	arg1	progression					249:259	G1 phase progression	240:259	G1 phase progression	240:259	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	8	13	theme	cyclin	1054:1059	arg1	D1					1061:1062	cyclin D1	1054:1062	cyclin D1	1054:1062	We conclude that O-GlcNAcylation promotes the stability of cyclin D1 through modulating its ubiquitination.
30853938	2	14	theme	G1	240:241	arg1	progression					249:259	G1 phase progression	240:259	G1 phase progression	240:259	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	7	15	theme	cancer	902:907	arg1	cells					909:913	human cancer cells	896:913	human cancer cells	896:913	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	3	16	theme	timely	315:320	arg1	activation					335:344	their timely and accurate activation	309:344	their timely and accurate activation	309:344	To ensure their timely and accurate activation during cell cycle progression, cyclin D1 turnover is finely controlled by phosphorylation and ubiquitination.
30853938	4	17	link	O-linked	501:508	arg1	β-N-Acetyl-glucosaminylation					510:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation	474:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation)	474:555	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	4	17	link	O-linked	501:508	arg1	O-GlcNAcylation					540:554	O-GlcNAcylation	540:554	O-GlcNAcylation	540:554	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	0	18	theme	Cyclin	0:5	arg1	D1					7:8	Cyclin D1	0:8	Cyclin D1 Stability	0:18	Cyclin D1 Stability Is Partly Controlled by O-GlcNAcylation.
30853938	0	19	theme	D1	7:8	arg1	Stability					10:18	Cyclin D1 Stability	0:18	Cyclin D1 Stability	0:18	Cyclin D1 Stability Is Partly Controlled by O-GlcNAcylation.
30853938	2	20	theme	extracellular	276:288	arg1	signals					290:296	extracellular signals	276:296	extracellular signals	276:296	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	7	21	theme	biochemical	852:862	arg1	experiments					881:891	biochemical and cell imaging experiments	852:891	experiments	881:891	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	2	22	dep	entry	230:234	arg1	the					215:217	the	215:217	the	215:217	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	3	23	theme	cycle	358:362	arg1	progression					364:374	cell cycle progression	353:374	cell cycle progression	353:374	To ensure their timely and accurate activation during cell cycle progression, cyclin D1 turnover is finely controlled by phosphorylation and ubiquitination.
30853938	5	24	theme	cyclin	640:645	arg1	D1					647:648	cyclin D1	640:648	cyclin D1	640:648	High O-GlcNAc levels increase the stability of cyclin D1, while reduction of O-GlcNAcylation strongly decreases it.
30853938	1	25	theme	regulatory	78:87	arg1	D1					68:69	Cyclin D1	61:69	Cyclin D1	61:69	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	25	theme	regulatory	78:87	arg1	partner					89:95	the regulatory partner	74:95	the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6	74:147	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	7	26	theme	O-GlcNAc	931:938	arg1	transferase					940:950	the O-GlcNAc transferase	927:950	the O-GlcNAc transferase (OGT)	927:956	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	7	26	theme	O-GlcNAc	931:938	arg1	OGT					953:955	OGT	953:955	OGT	953:955	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	7	27	gly	glycosylates	971:982	arg1	D1					991:992	cyclin D1	984:992	cyclin D1	984:992	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	2	28	from	entry	230:234	arg1	response					264:271	response	264:271	response to extracellular signals	264:296	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	3	29	theme	cyclin	377:382	arg1	D1					384:385	cyclin D1	377:385	cyclin D1 turnover	377:394	To ensure their timely and accurate activation during cell cycle progression, cyclin D1 turnover is finely controlled by phosphorylation and ubiquitination.
30853938	7	30	theme	cell	868:871	arg1	experiments					881:891	biochemical and cell imaging experiments	852:891	experiments	881:891	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	3	31	theme	D1	384:385	arg1	turnover					387:394	cyclin D1 turnover	377:394	cyclin D1 turnover	377:394	To ensure their timely and accurate activation during cell cycle progression, cyclin D1 turnover is finely controlled by phosphorylation and ubiquitination.
30853938	4	32	theme	O-linked	501:508	arg1	β-N-Acetyl-glucosaminylation					510:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation	474:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation)	474:555	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	4	32	theme	O-linked	501:508	arg1	O-GlcNAcylation					540:554	O-GlcNAcylation	540:554	O-GlcNAcylation	540:554	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	6	33	theme	OGA	769:771	arg1	inhibition					774:783	O-GlcNAcase (OGA) inhibition	756:783	O-GlcNAcase (OGA) inhibition	756:783	Moreover, elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition significantly slows down the ubiquitination of cyclin D1.
30853938	7	34	theme	cyclin	984:989	arg1	D1					991:992	cyclin D1	984:992	cyclin D1	984:992	Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1.
30853938	4	35	theme	reversible	490:499	arg1	β-N-Acetyl-glucosaminylation					510:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation	474:537	the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation)	474:555	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	4	35	theme	reversible	490:499	arg1	O-GlcNAcylation					540:554	O-GlcNAcylation	540:554	O-GlcNAcylation	540:554	Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life.
30853938	2	36	theme	D1/CDK	192:197	arg1	complexes					199:207	the cyclin D1/CDK complexes	181:207	the cyclin D1/CDK complexes	181:207	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	5	37	theme	O-GlcNAcylation	670:684	arg1	reduction					657:665	reduction	657:665	reduction of O-GlcNAcylation	657:684	High O-GlcNAc levels increase the stability of cyclin D1, while reduction of O-GlcNAcylation strongly decreases it.
30853938	2	38	theme	cyclin	185:190	arg1	complexes					199:207	the cyclin D1/CDK complexes	181:207	the cyclin D1/CDK complexes	181:207	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	6	39	theme	O-GlcNAcase	756:766	arg1	inhibition					774:783	O-GlcNAcase (OGA) inhibition	756:783	O-GlcNAcase (OGA) inhibition	756:783	Moreover, elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition significantly slows down the ubiquitination of cyclin D1.
30853938	1	40	theme	cyclin-dependent	104:119	arg1	kinases					121:127	cyclin-dependent kinases	104:127	the cyclin-dependent kinases (CDKs) CDK4 or CDK6	100:147	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	40	theme	cyclin-dependent	104:119	arg1	CDK6					144:147	CDK6	144:147	CDK6	144:147	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	40	theme	cyclin-dependent	104:119	arg1	CDK4					136:139	CDK4	136:139	CDK4	136:139	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	40	theme	cyclin-dependent	104:119	arg1	CDKs					130:133	CDKs	130:133	CDKs	130:133	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	41	theme	kinases	121:127	arg1	D1					68:69	Cyclin D1	61:69	Cyclin D1	61:69	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	1	41	theme	kinases	121:127	arg1	partner					89:95	the regulatory partner	74:95	the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6	74:147	Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6.
30853938	6	42	theme	D1	839:840	arg1	ubiquitination					814:827	the ubiquitination	810:827	the ubiquitination of cyclin D1	810:840	Moreover, elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition significantly slows down the ubiquitination of cyclin D1.
30853938	2	43	theme	cycle	224:228	arg1	entry					230:234	cell cycle entry	219:234	cell cycle entry	219:234	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	6	44	theme	levels	741:746	arg1	elevation					719:727	elevation	719:727	elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition	719:783	Moreover, elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition significantly slows down the ubiquitination of cyclin D1.
30853938	2	45	from	progression	249:259	arg1	response					264:271	response	264:271	response to extracellular signals	264:296	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	8	46	theme	D1	1061:1062	arg1	stability					1041:1049	the stability	1037:1049	the stability of cyclin D1	1037:1062	We conclude that O-GlcNAcylation promotes the stability of cyclin D1 through modulating its ubiquitination.
30853938	6	47	theme	cyclin	832:837	arg1	D1					839:840	cyclin D1	832:840	cyclin D1	832:840	Moreover, elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition significantly slows down the ubiquitination of cyclin D1.
30853938	2	48	theme	cell	219:222	arg1	entry					230:234	cell cycle entry	219:234	cell cycle entry	219:234	Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals.
30853938	6	49	theme	O-GlcNAc	732:739	arg1	levels					741:746	O-GlcNAc levels	732:746	O-GlcNAc levels	732:746	Moreover, elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition significantly slows down the ubiquitination of cyclin D1.
30853938	3	50	theme	cell	353:356	arg1	progression					364:374	cell cycle progression	353:374	cell cycle progression	353:374	To ensure their timely and accurate activation during cell cycle progression, cyclin D1 turnover is finely controlled by phosphorylation and ubiquitination.
29298676	6	0	theme	OnPLS	973:977	arg1	modeling					1025:1032	Multivariate OnPLS (orthogonal projections to latent structures) modeling	960:1032	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	960:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	4	1	theme	transgenic	607:616	arg1	trees					618:622	the transgenic trees	603:622	the transgenic trees	603:622	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	2	2	theme	trees	372:376	arg1	formation					351:359	wood formation	346:359	wood formation of Populus trees	346:376	A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees.
29298676	11	3	theme	SCAMP	2198:2202	arg1	proteins					2204:2211	the SCAMP proteins	2194:2211	the SCAMP proteins in plant stem tissues	2194:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	6	4	theme	systemic	1228:1235	arg1	variation					1237:1245	systemic variation	1228:1245	systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition	1228:1387	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	7	5	from	lines	1498:1502	arg1	abundant					1471:1478	abundant	1471:1478	abundant	1471:1478	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	9	6	theme	cell	1736:1739	arg1	components					1746:1755	secondary cell wall components	1726:1755	secondary cell wall components	1726:1755	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	9	6	theme	cell	1736:1739	arg1	polysaccharides					1768:1782	polysaccharides	1768:1782	polysaccharides	1768:1782	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	9	6	theme	cell	1736:1739	arg1	compounds					1797:1805	phenolic compounds	1788:1805	phenolic compounds	1788:1805	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	10	7	dep	fine-tune	1988:1996	arg1	abundance					2002:2010	the abundance	1998:2010	the abundance of cell wall precursors	1998:2034	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	6	8	theme	stem	1214:1217	arg1	tissues					1199:1205	the secondary xylem tissues	1179:1205	the secondary xylem tissues of the stem	1179:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	11	9	theme	future	2160:2165	arg1	studies					2167:2173	future studies	2160:2173	future studies on the function of the SCAMP proteins in plant stem tissues	2160:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	7	10	theme	wild	1516:1519	arg1	type					1521:1524	the wild type	1512:1524	the wild type	1512:1524	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	10	11	theme	precursors	2025:2034	arg1	abundance					2002:2010	the abundance	1998:2010	the abundance of cell wall precursors	1998:2034	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	2	12	theme	SCAMPs	336:341	arg1	function					324:331	function	324:331	function of SCAMPs in wood formation of Populus trees	324:376	A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees.
29298676	5	13	theme	cork	930:933	arg1	density					860:866	increased wood density	845:866	increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines	845:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	5	13	theme	cork	930:933	arg1	thickness					903:911	significantly increased thickness	879:911	increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines	845:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	9	14	theme	components	1746:1755	arg1	accumulation					1710:1721	accumulation	1710:1721	accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems	1710:1849	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	7	15	theme	proteins	1447:1454	arg1	number					1437:1442	a rather large number	1422:1442	a rather large number of proteins that were more abundant in the transgenic lines than in the wild type	1422:1524	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	10	16	theme	cell	2015:2018	arg1	precursors					2025:2034	cell wall precursors	2015:2034	cell wall precursors	2015:2034	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	4	17	theme	oligomers	687:695	arg1	amounts					644:650	increased amounts	634:650	increased amounts of both polysaccharides and lignin oligomers	634:695	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	4	17	theme	oligomers	687:695	arg1	polysaccharides					660:674	polysaccharides	660:674	polysaccharides	660:674	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	4	17	theme	oligomers	687:695	arg1	oligomers					687:695	lignin oligomers	680:695	lignin oligomers	680:695	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	11	18	from	studies	2167:2173	arg1	function					2182:2189	the function	2178:2189	the function of the SCAMP proteins in plant stem tissues	2178:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	10	19	theme	multi-omics	1856:1866	arg1	analyses					1868:1875	Our multi-omics analyses	1852:1875	Our multi-omics analyses combined with the OnPLS modelling	1852:1909	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	9	20	from	accumulation	1710:1721	arg1	tissues					1821:1827	the woody tissues	1811:1827	the woody tissues of Populus tree stems	1811:1849	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	6	21	theme	transgenic	1281:1290	arg1	lines					1292:1296	the transgenic lines	1277:1296	the transgenic lines	1277:1296	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	4	22	theme	lignin	759:764	arg1	components					766:775	both the carbohydrate and lignin components	733:775	components	766:775	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	6	23	theme	cell	1367:1370	arg1	composition					1377:1387	the secondary cell wall composition	1353:1387	the secondary cell wall composition	1353:1387	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	1	24	theme	BACKGROUND	132:141	arg1	proteins					230:237	highly conserved 32-38 kDa proteins	203:237	highly conserved 32-38 kDa proteins that are involved in membrane trafficking	203:279	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	24	theme	BACKGROUND	132:141	arg1	Proteins					181:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins	132:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs)	132:197	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	24	theme	BACKGROUND	132:141	arg1	SCAMPs					191:196	SCAMPs	191:196	SCAMPs	191:196	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	6	25	theme	orthogonal	980:989	arg1	projections					991:1001	orthogonal projections	980:1001	orthogonal projections to latent structures	980:1022	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	2	26	theme	systems	284:290	arg1	approach					292:299	A systems approach	282:299	A systems approach	282:299	A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees.
29298676	1	27	theme	Carrier-Associated	153:170	arg1	proteins					230:237	highly conserved 32-38 kDa proteins	203:237	highly conserved 32-38 kDa proteins that are involved in membrane trafficking	203:279	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	27	theme	Carrier-Associated	153:170	arg1	Proteins					181:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins	132:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs)	132:197	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	27	theme	Carrier-Associated	153:170	arg1	SCAMPs					191:196	SCAMPs	191:196	SCAMPs	191:196	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	6	28	theme	different	1254:1262	arg1	variables					1264:1272	the different variables	1250:1272	the different variables	1250:1272	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	28	theme	different	1254:1262	arg1	changes					1309:1315	changes	1309:1315	changes that correlated with the changes in the secondary cell wall composition	1309:1387	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	10	29	theme	wall	2069:2072	arg1	biosynthesis					2074:2085	cell wall biosynthesis	2064:2085	cell wall biosynthesis	2064:2085	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	0	30	theme	Membrane	72:79	arg1	Proteins					81:88	Secretory Carrier-Associated Membrane Proteins	43:88	Secretory Carrier-Associated Membrane Proteins	43:88	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	4	31	dep	RESULTS	574:580	arg1	displayed					624:632	displayed	624:632	displayed	624:632	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	7	32	from	abundant	1471:1478	arg1	type					1521:1524	the wild type	1512:1524	the wild type	1512:1524	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	7	32	from	abundant	1471:1478	arg1	lines					1498:1502	the transgenic lines	1483:1502	the transgenic lines	1483:1502	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	9	33	theme	woody	1815:1819	arg1	tissues					1821:1827	the woody tissues	1811:1827	the woody tissues of Populus tree stems	1811:1849	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	4	34	theme	carbohydrate	742:753	arg1	components					766:775	both the carbohydrate and lignin components	733:775	components	766:775	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	6	35	theme	omics	1052:1056	arg1	proteome					1087:1094	proteome	1087:1094	proteome	1087:1094	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	35	theme	omics	1052:1056	arg1	datasets					1058:1065	five different omics datasets	1037:1065	five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	1037:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	35	theme	omics	1052:1056	arg1	metabolome					1103:1112	GC-MS metabolome	1097:1112	GC-MS metabolome	1097:1112	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	35	theme	omics	1052:1056	arg1	metabolome					1152:1161	pyrolysis-GC/MS metabolome	1136:1161	pyrolysis-GC/MS metabolome	1136:1161	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	35	theme	omics	1052:1056	arg1	transcriptome					1072:1084	the transcriptome	1068:1084	the transcriptome	1068:1084	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	35	theme	omics	1052:1056	arg1	metabolome					1121:1130	LC-MS metabolome	1115:1130	LC-MS metabolome	1115:1130	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	3	36	theme	Phenotypic	379:388	arg1	analyses					406:413	Phenotypic and multi-omics analyses	379:413	Phenotypic and multi-omics analyses	379:413	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	6	37	from	variables	1264:1272	arg1	lines					1292:1296	the transgenic lines	1277:1296	the transgenic lines	1277:1296	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	0	38	theme	formation	98:106	arg1	​trees					124:129	wood formation of​ ​​Populus​​ ​trees	93:129	wood formation of​ ​​Populus​​ ​trees	93:129	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	9	39	theme	tree	1840:1843	arg1	stems					1845:1849	Populus tree stems	1832:1849	Populus tree stems	1832:1849	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	3	40	theme	trees	469:473	arg1	tissues					439:445	woody tissues	433:445	woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	433:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	0	41	theme	​​Populus​​	112:122	arg1	​trees					124:129	wood formation of​ ​​Populus​​ ​trees	93:129	wood formation of​ ​​Populus​​ ​trees	93:129	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	7	42	theme	OnPLS	1394:1398	arg1	model					1400:1404	The OnPLS model	1390:1404	The OnPLS model	1390:1404	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	11	43	theme	stem	2222:2225	arg1	tissues					2227:2233	plant stem tissues	2216:2233	plant stem tissues	2216:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	0	44	from	function	31:38	arg1	​trees					124:129	wood formation of​ ​​Populus​​ ​trees	93:129	wood formation of​ ​​Populus​​ ​trees	93:129	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	4	45	theme	secondary	784:792	arg1	walls					799:803	the secondary cell walls	780:803	the secondary cell walls	780:803	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	6	46	from	variation	1237:1245	arg1	variables					1264:1272	the different variables	1250:1272	the different variables	1250:1272	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	46	from	variation	1237:1245	arg1	changes					1309:1315	changes	1309:1315	changes that correlated with the changes in the secondary cell wall composition	1309:1387	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	3	47	theme	transgenic	450:459	arg1	trees					469:473	transgenic Populus trees	450:473	transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	450:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	3	48	theme	multi-omics	394:404	arg1	analyses					406:413	Phenotypic and multi-omics analyses	379:413	Phenotypic and multi-omics analyses	379:413	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	4	49	theme	walls	799:803	arg1	components					766:775	both the carbohydrate and lignin components	733:775	components	766:775	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	6	50	theme	GC-MS	1097:1101	arg1	metabolome					1103:1112	GC-MS metabolome	1097:1112	GC-MS metabolome	1097:1112	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	50	theme	GC-MS	1097:1101	arg1	datasets					1058:1065	five different omics datasets	1037:1065	five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	1037:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	8	51	theme	primary	1605:1611	arg1	biosynthesis					1637:1648	both primary and secondary cell wall biosynthesis	1600:1648	secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis	1560:1648	Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.
29298676	3	52	theme	x	522:522	arg1	SCAMP3					536:541	Populus tremula x tremuloides SCAMP3	506:541	Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	506:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	5	53	theme	increased	845:853	arg1	density					860:866	increased wood density	845:866	increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines	845:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	9	54	theme	CONCLUSIONS	1651:1661	arg1	proteins					1677:1684	CONCLUSIONS Populus SCAMP proteins	1651:1684	CONCLUSIONS Populus SCAMP proteins	1651:1684	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	6	55	theme	secondary	1183:1191	arg1	tissues					1199:1205	the secondary xylem tissues	1179:1205	the secondary xylem tissues of the stem	1179:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	8	56	theme	secondary	1617:1625	arg1	biosynthesis					1637:1648	both primary and secondary cell wall biosynthesis	1600:1648	secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis	1560:1648	Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.
29298676	6	57	dep	OnPLS	973:977	arg1	projections					991:1001	orthogonal projections	980:1001	orthogonal projections to latent structures	980:1022	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	9	58	theme	SCAMP	1671:1675	arg1	proteins					1677:1684	CONCLUSIONS Populus SCAMP proteins	1651:1684	CONCLUSIONS Populus SCAMP proteins	1651:1684	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	4	59	theme	increased	634:642	arg1	amounts					644:650	increased amounts	634:650	increased amounts of both polysaccharides and lignin oligomers	634:695	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	4	59	theme	increased	634:642	arg1	polysaccharides					660:674	polysaccharides	660:674	polysaccharides	660:674	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	4	59	theme	increased	634:642	arg1	oligomers					687:695	lignin oligomers	680:695	lignin oligomers	680:695	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	1	60	theme	membrane	260:267	arg1	trafficking					269:279	membrane trafficking	260:279	membrane trafficking	260:279	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	10	61	theme	membrane	1964:1971	arg1	trafficking					1973:1983	membrane trafficking	1964:1983	membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport	1964:2099	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	6	62	theme	Multivariate	960:971	arg1	OnPLS					973:977	Multivariate OnPLS	960:977	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	960:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	63	theme	pyrolysis-GC/MS	1136:1150	arg1	datasets					1058:1065	five different omics datasets	1037:1065	five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	1037:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	63	theme	pyrolysis-GC/MS	1136:1150	arg1	metabolome					1152:1161	pyrolysis-GC/MS metabolome	1136:1161	pyrolysis-GC/MS metabolome	1136:1161	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	7	64	theme	transgenic	1487:1496	arg1	lines					1498:1502	the transgenic lines	1483:1502	the transgenic lines	1483:1502	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	4	65	theme	trees	618:622	arg1	tissues					592:598	The woody tissues	582:598	The woody tissues of the transgenic trees	582:622	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	2	66	theme	Populus	364:370	arg1	trees					372:376	Populus trees	364:376	Populus trees	364:376	A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees.
29298676	0	67	theme	Secretory	43:51	arg1	Proteins					81:88	Secretory Carrier-Associated Membrane Proteins	43:88	Secretory Carrier-Associated Membrane Proteins	43:88	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	9	68	theme	secondary	1726:1734	arg1	components					1746:1755	secondary cell wall components	1726:1755	secondary cell wall components	1726:1755	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	9	68	theme	secondary	1726:1734	arg1	polysaccharides					1768:1782	polysaccharides	1768:1782	polysaccharides	1768:1782	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	9	68	theme	secondary	1726:1734	arg1	compounds					1797:1805	phenolic compounds	1788:1805	phenolic compounds	1788:1805	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	11	69	from	tissues	2227:2233	arg1	function					2182:2189	the function	2178:2189	the function of the SCAMP proteins in plant stem tissues	2178:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	5	70	theme	suberized	920:928	arg1	cork					930:933	the suberized cork	916:933	the suberized cork	916:933	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	10	71	from	changes	1953:1959	arg1	trafficking					1973:1983	membrane trafficking	1964:1983	membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport	1964:2099	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	9	72	theme	wall	1741:1744	arg1	components					1746:1755	secondary cell wall components	1726:1755	secondary cell wall components	1726:1755	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	9	72	theme	wall	1741:1744	arg1	polysaccharides					1768:1782	polysaccharides	1768:1782	polysaccharides	1768:1782	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	9	72	theme	wall	1741:1744	arg1	compounds					1797:1805	phenolic compounds	1788:1805	phenolic compounds	1788:1805	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	4	73	theme	increased	709:717	arg1	deposition					719:728	increased deposition	709:728	increased deposition of both the carbohydrate and lignin components of the secondary cell walls	709:803	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	10	74	theme	wall	2020:2023	arg1	precursors					2025:2034	cell wall precursors	2015:2034	cell wall precursors	2015:2034	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	1	75	theme	32-38 kDa	220:228	arg1	proteins					230:237	highly conserved 32-38 kDa proteins	203:237	highly conserved 32-38 kDa proteins that are involved in membrane trafficking	203:279	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	75	theme	32-38 kDa	220:228	arg1	Proteins					181:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins	132:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs)	132:197	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	4	76	theme	polysaccharides	660:674	arg1	amounts					644:650	increased amounts	634:650	increased amounts of both polysaccharides and lignin oligomers	634:695	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	4	76	theme	polysaccharides	660:674	arg1	polysaccharides					660:674	polysaccharides	660:674	polysaccharides	660:674	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	4	76	theme	polysaccharides	660:674	arg1	oligomers					687:695	lignin oligomers	680:695	lignin oligomers	680:695	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	11	77	from	proteins	2204:2211	arg1	tissues					2227:2233	plant stem tissues	2216:2233	plant stem tissues	2216:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	1	78	theme	conserved	210:218	arg1	proteins					230:237	highly conserved 32-38 kDa proteins	203:237	highly conserved 32-38 kDa proteins that are involved in membrane trafficking	203:279	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	78	theme	conserved	210:218	arg1	Proteins					181:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins	132:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs)	132:197	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	5	79	theme	increased	893:901	arg1	thickness					903:911	significantly increased thickness	879:911	increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines	845:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	7	80	from	type	1521:1524	arg1	abundant					1471:1478	abundant	1471:1478	abundant	1471:1478	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	6	81	theme	latent	1006:1011	arg1	structures					1013:1022	latent structures	1006:1022	latent structures	1006:1022	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	4	82	theme	lignin	680:685	arg1	oligomers					687:695	lignin oligomers	680:695	lignin oligomers	680:695	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	6	83	theme	wall	1372:1375	arg1	composition					1377:1387	the secondary cell wall composition	1353:1387	the secondary cell wall composition	1353:1387	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	5	84	from	thickness	903:911	arg1	lines					953:957	the transgenic lines	938:957	the transgenic lines	938:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	9	85	theme	phenolic	1788:1795	arg1	compounds					1797:1805	phenolic compounds	1788:1805	phenolic compounds	1788:1805	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	7	86	theme	large	1431:1435	arg1	number					1437:1442	a rather large number	1422:1442	a rather large number of proteins that were more abundant in the transgenic lines than in the wild type	1422:1524	The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type.
29298676	11	87	from	function	2182:2189	arg1	tissues					2227:2233	plant stem tissues	2216:2233	plant stem tissues	2216:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	6	88	theme	secondary	1357:1365	arg1	composition					1377:1387	the secondary cell wall composition	1353:1387	the secondary cell wall composition	1353:1387	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	10	89	theme	OnPLS	1895:1899	arg1	modelling					1901:1909	the OnPLS modelling	1891:1909	the OnPLS modelling	1891:1909	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	1	90	theme	Secretory	143:151	arg1	proteins					230:237	highly conserved 32-38 kDa proteins	203:237	highly conserved 32-38 kDa proteins that are involved in membrane trafficking	203:279	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	90	theme	Secretory	143:151	arg1	Proteins					181:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins	132:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs)	132:197	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	90	theme	Secretory	143:151	arg1	SCAMPs					191:196	SCAMPs	191:196	SCAMPs	191:196	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	11	91	theme	information	2144:2154	arg1	source					2134:2139	a multi-level source	2120:2139	a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues	2120:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	3	92	contain	carrying	475:482	arg1	trees					469:473	transgenic Populus trees	450:473	transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	450:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	3	92	contain	carrying	475:482	arg2	construct					492:500	an RNAi construct	484:500	an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	484:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	4	93	theme	components	766:775	arg1	deposition					719:728	increased deposition	709:728	increased deposition of both the carbohydrate and lignin components of the secondary cell walls	709:803	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	3	94	theme	Populus	506:512	arg1	SCAMP3					536:541	Populus tremula x tremuloides SCAMP3	506:541	Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	506:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	0	95	theme	Proteins	81:88	arg1	function					31:38	function	31:38	function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees	31:129	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	11	96	theme	multi-level	2122:2132	arg1	source					2134:2139	a multi-level source	2120:2139	a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues	2120:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	1	97	theme	Membrane	172:179	arg1	proteins					230:237	highly conserved 32-38 kDa proteins	203:237	highly conserved 32-38 kDa proteins that are involved in membrane trafficking	203:279	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	97	theme	Membrane	172:179	arg1	Proteins					181:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins	132:188	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs)	132:197	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	1	97	theme	Membrane	172:179	arg1	SCAMPs					191:196	SCAMPs	191:196	SCAMPs	191:196	BACKGROUND Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking.
29298676	8	98	theme	these	1538:1542	arg1	Several					1527:1533	Several	1527:1533	Several	1527:1533	Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.
29298676	10	99	theme	cell	2064:2067	arg1	biosynthesis					2074:2085	cell wall biosynthesis	2064:2085	cell wall biosynthesis	2064:2085	Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport.
29298676	0	100	theme	wood	93:96	arg1	​trees					124:129	wood formation of​ ​​Populus​​ ​trees	93:129	wood formation of​ ​​Populus​​ ​trees	93:129	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	5	101	theme	transgenic	942:951	arg1	lines					953:957	the transgenic lines	938:957	the transgenic lines	938:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	2	102	from	function	324:331	arg1	formation					351:359	wood formation	346:359	wood formation of Populus trees	346:376	A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees.
29298676	6	103	theme	datasets	1058:1065	arg1	modeling					1025:1032	Multivariate OnPLS (orthogonal projections to latent structures) modeling	960:1032	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	960:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	104	dep	datasets	1058:1065	arg1	proteome					1087:1094	proteome	1087:1094	proteome	1087:1094	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	104	dep	datasets	1058:1065	arg1	datasets					1058:1065	five different omics datasets	1037:1065	five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	1037:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	104	dep	datasets	1058:1065	arg1	metabolome					1103:1112	GC-MS metabolome	1097:1112	GC-MS metabolome	1097:1112	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	104	dep	datasets	1058:1065	arg1	metabolome					1152:1161	pyrolysis-GC/MS metabolome	1136:1161	pyrolysis-GC/MS metabolome	1136:1161	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	104	dep	datasets	1058:1065	arg1	transcriptome					1072:1084	the transcriptome	1068:1084	the transcriptome	1068:1084	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	104	dep	datasets	1058:1065	arg1	metabolome					1121:1130	LC-MS metabolome	1115:1130	LC-MS metabolome	1115:1130	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	0	105	theme	of​	108:110	arg1	​trees					124:129	wood formation of​ ​​Populus​​ ​trees	93:129	wood formation of​ ​​Populus​​ ​trees	93:129	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	3	106	dep	Populus	506:512	arg1	tremula					514:520	tremula	514:520	tremula	514:520	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	6	107	theme	different	1042:1050	arg1	proteome					1087:1094	proteome	1087:1094	proteome	1087:1094	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	107	theme	different	1042:1050	arg1	datasets					1058:1065	five different omics datasets	1037:1065	five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	1037:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	107	theme	different	1042:1050	arg1	metabolome					1103:1112	GC-MS metabolome	1097:1112	GC-MS metabolome	1097:1112	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	107	theme	different	1042:1050	arg1	metabolome					1152:1161	pyrolysis-GC/MS metabolome	1136:1161	pyrolysis-GC/MS metabolome	1136:1161	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	107	theme	different	1042:1050	arg1	transcriptome					1072:1084	the transcriptome	1068:1084	the transcriptome	1068:1084	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	107	theme	different	1042:1050	arg1	metabolome					1121:1130	LC-MS metabolome	1115:1130	LC-MS metabolome	1115:1130	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	9	108	theme	Populus	1832:1838	arg1	stems					1845:1849	Populus tree stems	1832:1849	Populus tree stems	1832:1849	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	9	109	theme	stems	1845:1849	arg1	tissues					1821:1827	the woody tissues	1811:1827	the woody tissues of Populus tree stems	1811:1849	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	11	110	theme	proteins	2204:2211	arg1	function					2182:2189	the function	2178:2189	the function of the SCAMP proteins in plant stem tissues	2178:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	8	111	theme	wall	1632:1635	arg1	biosynthesis					1637:1648	both primary and secondary cell wall biosynthesis	1600:1648	secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis	1560:1648	Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.
29298676	0	112	theme	multi-omics	2:12	arg1	approach					14:21	A multi-omics approach	0:21	A multi-omics approach	0:21	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	5	113	from	density	860:866	arg1	lines					953:957	the transgenic lines	938:957	the transgenic lines	938:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	3	114	dep	SCAMP3	536:541	arg1	PttSCAMP3					544:552	PttSCAMP3	544:552	PttSCAMP3; Potri.019G104000	544:570	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	6	115	theme	LC-MS	1115:1119	arg1	datasets					1058:1065	five different omics datasets	1037:1065	five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem	1037:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	6	115	theme	LC-MS	1115:1119	arg1	metabolome					1121:1130	LC-MS metabolome	1115:1130	LC-MS metabolome	1115:1130	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	4	116	theme	woody	586:590	arg1	tissues					592:598	The woody tissues	582:598	The woody tissues of the transgenic trees	582:622	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	3	117	theme	Populus	461:467	arg1	trees					469:473	transgenic Populus trees	450:473	transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	450:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	3	118	dep	PttSCAMP3	544:552	arg1	Potri.019G104000					555:570	Potri.019G104000	555:570	PttSCAMP3; Potri.019G104000	544:570	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	11	119	theme	plant	2216:2220	arg1	tissues					2227:2233	plant stem tissues	2216:2233	plant stem tissues	2216:2233	The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.
29298676	4	120	theme	cell	794:797	arg1	walls					799:803	the secondary cell walls	780:803	the secondary cell walls	780:803	RESULTS The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls.
29298676	3	121	theme	RNAi	487:490	arg1	construct					492:500	an RNAi construct	484:500	an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	484:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	0	122	theme	Carrier-Associated	53:70	arg1	Proteins					81:88	Secretory Carrier-Associated Membrane Proteins	43:88	Secretory Carrier-Associated Membrane Proteins	43:88	A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.
29298676	6	123	theme	xylem	1193:1197	arg1	tissues					1199:1205	the secondary xylem tissues	1179:1205	the secondary xylem tissues of the stem	1179:1217	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
29298676	3	124	theme	woody	433:437	arg1	tissues					439:445	woody tissues	433:445	woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	433:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	8	125	theme	cell	1627:1630	arg1	biosynthesis					1637:1648	both primary and secondary cell wall biosynthesis	1600:1648	secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis	1560:1648	Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.
29298676	3	126	theme	tremuloides	524:534	arg1	SCAMP3					536:541	Populus tremula x tremuloides SCAMP3	506:541	Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000)	506:571	Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).
29298676	9	127	theme	Populus	1663:1669	arg1	proteins					1677:1684	CONCLUSIONS Populus SCAMP proteins	1651:1684	CONCLUSIONS Populus SCAMP proteins	1651:1684	CONCLUSIONS Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems.
29298676	2	128	theme	wood	346:349	arg1	formation					351:359	wood formation	346:359	wood formation of Populus trees	346:376	A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees.
29298676	5	129	theme	wood	855:858	arg1	density					860:866	increased wood density	845:866	increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines	845:957	This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines.
29298676	6	130	from	changes	1342:1348	arg1	composition					1377:1387	the secondary cell wall composition	1353:1387	the secondary cell wall composition	1353:1387	Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition.
30759596	2	0	theme	positive	425:432	arg1	control					434:440	the positive control	421:440	the positive control	421:440	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	2	0	theme	positive	425:432	arg1	NPs					340:342	CuO NPs	336:342	CuO NPs (1 mg/L uncoated and humic-acid-coated)	336:382	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	6	1	theme	Functional	935:944	arg1	analysis					946:953	Functional analysis	935:953	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes	935:1071	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	3	2	theme	oxygen	668:673	arg1	respiration					675:685	the oxygen respiration	664:685	the oxygen respiration activity	664:694	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	6	3	theme	PICRUSt	960:966	arg1	metagenomes					1061:1071	PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes	960:1071	PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes	960:1071	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	6	4	dep	PICRUSt	960:966	arg1	Investigation					982:994	Phylogenetic Investigation	969:994	Phylogenetic Investigation of Communities by Reconstruction of Unobserved States	969:1048	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	3	5	theme	NP	618:619	arg1	additions					621:629	NP additions	618:629	NP additions	618:629	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	6	6	from	metagenomes	1061:1071	arg1	analysis					946:953	Functional analysis	935:953	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes	935:1071	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	2	7	theme	CuO	336:338	arg1	control					434:440	the positive control	421:440	the positive control	421:440	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	2	7	theme	CuO	336:338	arg1	NPs					340:342	CuO NPs	336:342	CuO NPs (1 mg/L uncoated and humic-acid-coated)	336:382	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	6	8	theme	Phylogenetic	969:980	arg1	Investigation					982:994	Phylogenetic Investigation	969:994	Phylogenetic Investigation of Communities by Reconstruction of Unobserved States	969:1048	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	0	9	theme	sediment	101:108	arg1	biofilms					110:117	sediment biofilms	101:117	sediment biofilms	101:117	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	8	10	theme	organic	1671:1677	arg1	matters					1679:1685	natural organic matters	1663:1685	natural organic matters such as humic acid	1663:1704	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	8	10	theme	organic	1671:1677	arg1	acid					1701:1704	humic acid	1695:1704	humic acid	1695:1704	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	1	11	from	effects	155:161	arg1	biofilms					212:219	freshwater sediment biofilms	192:219	freshwater sediment biofilms in terms of the functional properties and microbial community structure	192:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	2	12	dep	NPs	340:342	arg1	1 mg/L					345:350	1 mg/L	345:350	1 mg/L uncoated and humic-acid-coated	345:381	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	8	13	theme	humic	1695:1699	arg1	acid					1701:1704	humic acid	1695:1704	humic acid	1695:1704	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	8	14	theme	toxic	1573:1577	arg1	effects					1579:1585	Whereas these toxic effects	1559:1585	Whereas these toxic effects of CuO NPs	1559:1596	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	7	15	theme	negative	1451:1458	arg1	effects					1460:1466	negative effects	1451:1466	negative effects on the biogeochemical processes	1451:1498	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	16	theme	functional	1259:1268	arg1	profiles					1270:1277	These functional profiles	1253:1277	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP),	1253:1398	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	17	theme	NPs	1439:1441	arg1	introduction					1419:1430	the introduction	1415:1430	the introduction of CuO NPs	1415:1441	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	1	18	theme	functional	237:246	arg1	properties					248:257	the functional properties	233:257	the functional properties	233:257	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	7	19	theme	biogeochemical	1475:1488	arg1	processes					1490:1498	the biogeochemical processes	1471:1498	the biogeochemical processes	1471:1498	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	20	theme	CuO	1435:1437	arg1	NPs					1439:1441	CuO NPs	1435:1441	CuO NPs	1435:1441	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	5	21	theme	bacterial	807:815	arg1	composition					827:837	the bacterial community composition	803:837	the bacterial community composition	803:837	CuO NPs significantly altered the bacterial community composition and decreased the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea.
30759596	0	22	theme	biofilms	110:117	arg1	function					89:96	function	89:96	function	89:96	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	0	22	theme	biofilms	110:117	arg1	structure					75:83	microbial community structure	55:83	microbial community structure	55:83	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	3	23	theme	dissolved	466:474	arg1	oxygen					476:481	dissolved oxygen	466:481	dissolved oxygen	466:481	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	3	23	theme	dissolved	466:474	arg1	DO					462:463	DO	462:463	DO	462:463	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	6	24	theme	bacterial	1088:1096	arg1	genera					1098:1103	bacterial genera	1088:1103	bacterial genera depleted by CuO NP treatments	1088:1133	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	1	25	theme	copper	166:171	arg1	oxide					173:177	copper oxide	166:177	copper oxide (CuO) NPs	166:187	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	1	25	theme	copper	166:171	arg1	CuO					180:182	CuO	180:182	CuO	180:182	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	4	26	with	consistent	716:725	arg1	respiration					760:770	the decreased heterotrophic respiration	732:770	the decreased heterotrophic respiration	732:770	These results were consistent with the decreased heterotrophic respiration.
30759596	3	27	theme	CuO	648:650	arg1	NPs					652:654	CuO NPs	648:654	CuO NPs	648:654	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	3	28	theme	respiration	675:685	arg1	activity					687:694	the oxygen respiration activity	664:694	the oxygen respiration activity	664:694	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	5	29	theme	Aminicenantes	903:915	arg1	abundances					857:866	the abundances	853:866	the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea	853:932	CuO NPs significantly altered the bacterial community composition and decreased the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea.
30759596	1	30	theme	oxide	173:177	arg1	NPs					185:187	copper oxide (CuO) NPs	166:187	copper oxide (CuO) NPs	166:187	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	0	31	theme	Low	0:2	arg1	concentrations					4:17	Low concentrations	0:17	Low concentrations of copper oxide nanoparticles	0:47	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	1	32	theme	properties	248:257	arg1	terms					224:228	terms	224:228	terms of the functional properties and microbial community structure	224:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	5	33	theme	community	817:825	arg1	composition					827:837	the bacterial community composition	803:837	the bacterial community composition	803:837	CuO NPs significantly altered the bacterial community composition and decreased the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea.
30759596	2	34	theme	uncoated	352:359	arg1	1 mg/L					345:350	1 mg/L	345:350	1 mg/L uncoated and humic-acid-coated	345:381	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	0	35	theme	copper	22:27	arg1	nanoparticles					35:47	copper oxide nanoparticles	22:47	copper oxide nanoparticles	22:47	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	8	36	theme	Whereas	1559:1565	arg1	effects					1579:1585	Whereas these toxic effects	1559:1585	Whereas these toxic effects of CuO NPs	1559:1596	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	3	37	theme	microelectrodes	484:498	arg1	measurements					500:511	DO (dissolved oxygen) microelectrodes measurements	462:511	DO (dissolved oxygen) microelectrodes measurements	462:511	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	7	38	theme	enzymes	1335:1341	arg1	activities					1307:1316	the decreased activities	1293:1316	the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP),	1293:1398	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	5	39	theme	CuO	773:775	arg1	NPs					777:779	CuO NPs	773:779	CuO NPs	773:779	CuO NPs significantly altered the bacterial community composition and decreased the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea.
30759596	1	40	theme	microbial	263:271	arg1	structure					283:291	microbial community structure	263:291	microbial community structure	263:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	5	41	theme	Anaerolinea	922:932	arg1	abundances					857:866	the abundances	853:866	the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea	853:932	CuO NPs significantly altered the bacterial community composition and decreased the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea.
30759596	6	42	theme	States	1043:1048	arg1	Reconstruction					1014:1027	Reconstruction	1014:1027	Reconstruction of Unobserved States	1014:1048	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	0	43	theme	nanoparticles	35:47	arg1	concentrations					4:17	Low concentrations	0:17	Low concentrations of copper oxide nanoparticles	0:47	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	1	44	theme	community	273:281	arg1	structure					283:291	microbial community structure	263:291	microbial community structure	263:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	6	45	theme	secondary	1230:1238	arg1	metabolites					1240:1250	other secondary metabolites	1224:1250	other secondary metabolites	1224:1250	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	6	46	theme	Unobserved	1032:1041	arg1	States					1043:1048	Unobserved States	1032:1048	Unobserved States	1032:1048	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	6	47	theme	-predicted	1050:1059	arg1	metagenomes					1061:1071	PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes	960:1071	PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes	960:1071	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	1	48	theme	NPs	185:187	arg1	effects					155:161	the effects	151:161	the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure	151:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	0	49	theme	oxide	29:33	arg1	nanoparticles					35:47	copper oxide nanoparticles	22:47	copper oxide nanoparticles	22:47	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	1	50	theme	structure	283:291	arg1	terms					224:228	terms	224:228	terms of the functional properties and microbial community structure	224:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	8	51	theme	aquatic	1626:1632	arg1	environment					1634:1644	the aquatic environment	1622:1644	the aquatic environment	1622:1644	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	2	52	theme	Cu	408:409	arg1	NO3					411:413	Cu(NO3)2	408:415	Cu(NO3)2	408:415	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	2	52	theme	Cu	408:409	arg1	Cu2+					402:405	Cu2+	402:405	Cu2+ (Cu(NO3)2)	402:416	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	7	53	theme	extracellular	1321:1333	arg1	enzymes					1335:1341	extracellular enzymes	1321:1341	extracellular enzymes	1321:1341	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	53	theme	extracellular	1321:1333	arg1	β-glucosidase					1344:1356	β-glucosidase	1344:1356	β-glucosidase (GLU)	1344:1362	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	53	theme	extracellular	1321:1333	arg1	LAP					1394:1396	l-leucine aminopeptidase (LAP)	1368:1397	l-leucine aminopeptidase (LAP)	1368:1397	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	0	54	theme	microbial	55:63	arg1	structure					75:83	microbial community structure	55:83	microbial community structure	55:83	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	3	55	dep	suggested	638:646	arg1	inhibit					656:662	inhibit	656:662	suggested CuO NPs inhibit the oxygen respiration activity	638:694	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	1	56	from	biofilms	212:219	arg1	terms					224:228	terms	224:228	terms of the functional properties and microbial community structure	224:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	7	57	theme	biofilm	1542:1548	arg1	systems					1550:1556	biofilm systems	1542:1556	biofilm systems	1542:1556	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	3	58	theme	high-DO	516:522	arg1	region					524:529	a high-DO region	514:529	a high-DO region emerged inside the biofilms after 5-day exposure to CuO	514:585	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	5	59	theme	Anaerolineaceae	871:885	arg1	abundances					857:866	the abundances	853:866	the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea	853:932	CuO NPs significantly altered the bacterial community composition and decreased the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea.
30759596	7	60	from	cycling	1508:1514	arg1	processes					1490:1498	the biogeochemical processes	1471:1498	the biogeochemical processes	1471:1498	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	6	61	theme	metabolites	1240:1250	arg1	carbohydrate					1151:1162	carbohydrate	1151:1162	carbohydrate	1151:1162	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	6	61	theme	metabolites	1240:1250	arg1	biosynthesis					1208:1219	biosynthesis	1208:1219	biosynthesis	1208:1219	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	6	61	theme	metabolites	1240:1250	arg1	biosynthesis					1175:1186	glycan biosynthesis	1168:1186	glycan biosynthesis	1168:1186	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	6	61	theme	metabolites	1240:1250	arg1	metabolism					1192:1201	metabolism	1192:1201	metabolism	1192:1201	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	8	62	theme	CuO	1590:1592	arg1	NPs					1594:1596	CuO NPs	1590:1596	CuO NPs	1590:1596	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	6	63	theme	other	1224:1228	arg1	metabolites					1240:1250	other secondary metabolites	1224:1250	other secondary metabolites	1224:1250	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	7	64	theme	decreased	1297:1305	arg1	activities					1307:1316	the decreased activities	1293:1316	the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP),	1293:1398	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	8	65	theme	NPs	1594:1596	arg1	effects					1579:1585	Whereas these toxic effects	1559:1585	Whereas these toxic effects of CuO NPs	1559:1596	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	8	66	theme	natural	1663:1669	arg1	matters					1679:1685	natural organic matters	1663:1685	natural organic matters such as humic acid	1663:1704	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	8	66	theme	natural	1663:1669	arg1	acid					1701:1704	humic acid	1695:1704	humic acid	1695:1704	Whereas these toxic effects of CuO NPs could be mitigated when the aquatic environment is enriched with natural organic matters such as humic acid.
30759596	7	67	from	effects	1460:1466	arg1	processes					1490:1498	the biogeochemical processes	1471:1498	the biogeochemical processes	1471:1498	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	68	theme	nitrogen	1530:1537	arg1	effects					1460:1466	negative effects	1451:1466	negative effects on the biogeochemical processes	1451:1498	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	68	theme	nitrogen	1530:1537	arg1	cycling					1508:1514	the cycling	1504:1514	the cycling of carbon and nitrogen	1504:1537	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	69	theme	aminopeptidase	1378:1391	arg1	enzymes					1335:1341	extracellular enzymes	1321:1341	extracellular enzymes	1321:1341	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	69	theme	aminopeptidase	1378:1391	arg1	LAP					1394:1396	l-leucine aminopeptidase (LAP)	1368:1397	l-leucine aminopeptidase (LAP)	1368:1397	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	4	70	theme	heterotrophic	746:758	arg1	respiration					760:770	the decreased heterotrophic respiration	732:770	the decreased heterotrophic respiration	732:770	These results were consistent with the decreased heterotrophic respiration.
30759596	5	71	theme	Acidobacteria	888:900	arg1	abundances					857:866	the abundances	853:866	the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea	853:932	CuO NPs significantly altered the bacterial community composition and decreased the abundances of Anaerolineaceae, Acidobacteria, Aminicenantes, and Anaerolinea.
30759596	1	72	theme	freshwater	192:201	arg1	biofilms					212:219	freshwater sediment biofilms	192:219	freshwater sediment biofilms in terms of the functional properties and microbial community structure	192:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	6	73	theme	glycan	1168:1173	arg1	biosynthesis					1175:1186	glycan biosynthesis	1168:1186	glycan biosynthesis	1168:1186	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	3	74	theme	5-day	565:569	arg1	exposure					571:578	5-day exposure	565:578	5-day exposure to CuO	565:585	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
30759596	6	75	theme	CuO	1117:1119	arg1	treatments					1124:1133	CuO NP treatments	1117:1133	CuO NP treatments	1117:1133	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	1	76	theme	sediment	203:210	arg1	biofilms					212:219	freshwater sediment biofilms	192:219	freshwater sediment biofilms in terms of the functional properties and microbial community structure	192:291	In this study, we investigated the effects of copper oxide (CuO) NPs on freshwater sediment biofilms in terms of the functional properties and microbial community structure.
30759596	7	77	theme	carbon	1519:1524	arg1	effects					1460:1466	negative effects	1451:1466	negative effects on the biogeochemical processes	1451:1498	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	77	theme	carbon	1519:1524	arg1	cycling					1508:1514	the cycling	1504:1514	the cycling of carbon and nitrogen	1504:1537	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	4	78	theme	decreased	736:744	arg1	respiration					760:770	the decreased heterotrophic respiration	732:770	the decreased heterotrophic respiration	732:770	These results were consistent with the decreased heterotrophic respiration.
30759596	2	79	theme	humic-acid-coated	365:381	arg1	1 mg/L					345:350	1 mg/L	345:350	1 mg/L uncoated and humic-acid-coated	345:381	Biofilms were incubated in microcosms and CuO NPs (1 mg/L uncoated and humic-acid-coated) were exposed with Cu2+ (Cu(NO3)2) as the positive control.
30759596	6	80	theme	Communities	999:1009	arg1	Investigation					982:994	Phylogenetic Investigation	969:994	Phylogenetic Investigation of Communities by Reconstruction of Unobserved States	969:1048	Functional analysis from PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States)-predicted metagenomes indicated that bacterial genera depleted by CuO NP treatments were related to carbohydrate and glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites.
30759596	0	81	theme	community	65:73	arg1	structure					75:83	microbial community structure	55:83	microbial community structure	55:83	Low concentrations of copper oxide nanoparticles alter microbial community structure and function of sediment biofilms.
30759596	7	82	theme	l-leucine	1368:1376	arg1	enzymes					1335:1341	extracellular enzymes	1321:1341	extracellular enzymes	1321:1341	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	7	82	theme	l-leucine	1368:1376	arg1	LAP					1394:1396	l-leucine aminopeptidase (LAP)	1368:1397	l-leucine aminopeptidase (LAP)	1368:1397	These functional profiles combined with the decreased activities of extracellular enzymes, β-glucosidase (GLU) and l-leucine aminopeptidase (LAP), suggested that the introduction of CuO NPs exhibit negative effects on the biogeochemical processes and the cycling of carbon and nitrogen in biofilm systems.
30759596	3	83	theme	DO	462:463	arg1	measurements					500:511	DO (dissolved oxygen) microelectrodes measurements	462:511	DO (dissolved oxygen) microelectrodes measurements	462:511	As determined from DO (dissolved oxygen) microelectrodes measurements, a high-DO region emerged inside the biofilms after 5-day exposure to CuO NPs compared with those before NP additions, which suggested CuO NPs inhibit the oxygen respiration activity.
31076402	1	0	theme	human	177:181	arg1	hepatocytes					183:193	human hepatocytes	177:193	human hepatocytes	177:193	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	9	1	dep	CONCLUSION	1307:1316	arg1	miR-619-3p					1333:1342	miR-619-3p	1333:1342	miR-619-3p	1333:1342	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	1	dep	CONCLUSION	1307:1316	arg1	miR-501-3p					1318:1327	miR-501-3p	1318:1327	miR-501-3p	1318:1327	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	10	2	theme	liver	1534:1538	arg1	disease					1540:1546	HCV-induced liver disease	1522:1546	HCV-induced liver disease	1522:1546	In addition to its effect on HCV morphogenesis, OGT may play a role in HCV-induced liver disease and hepatocarcinogenesis.
31076402	7	3	theme	HCV	1144:1146	arg1	morphogenesis					1148:1160	HCV morphogenesis	1144:1160	HCV morphogenesis	1144:1160	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	1	4	theme	hepatocytes	183:193	arg1	process					241:247	a multistep process	229:247	a multistep process involving both viral and host factors	229:285	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	1	4	theme	hepatocytes	183:193	arg1	Infection					164:172	OBJECTIVE Infection	154:172	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV)	154:224	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	8	5	theme	liver	1281:1285	arg1	disease					1287:1293	HCV-induced liver disease	1269:1293	HCV-induced liver disease	1269:1293	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	8	6	theme	HCV-induced	1269:1279	arg1	disease					1287:1293	HCV-induced liver disease	1269:1293	HCV-induced liver disease	1269:1293	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	0	7	theme	C	115:115	arg1	virus					117:121	hepatitis C virus	105:121	hepatitis C virus morphogenesis	105:135	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	1	8	dep	factors	279:285	arg1	both					259:262	both	259:262	both	259:262	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	1	8	dep	factors	279:285	arg1	host					274:277	host	274:277	host	274:277	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	8	9	link	patient-derived	1220:1234	arg1	tissue					1242:1247	patient-derived liver tissue	1220:1247	patient-derived liver tissue	1220:1247	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	3	10	theme	regulatory	515:524	arg1	role					526:529	the functional and regulatory role	496:529	the functional and regulatory role of miRNAs for the HCV life cycle	496:562	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	4	11	theme	Huh7.5.1	713:720	arg1	cells					722:726	Huh7.5.1 cells	713:726	Huh7.5.1 cells infected with recombinant cell culture-derived HCV	713:777	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	0	12	theme	hepatitis	105:113	arg1	virus					117:121	hepatitis C virus	105:121	hepatitis C virus morphogenesis	105:135	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	9	13	theme	target	1354:1359	arg1	OGT					1361:1363	their target OGT	1348:1363	their target OGT	1348:1363	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	13	theme	target	1354:1359	arg1	factors					1409:1415	previously undiscovered regulatory host factors	1369:1415	previously undiscovered regulatory host factors for HCV assembly and infectivity	1369:1448	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	13	theme	target	1354:1359	arg1	CONCLUSION					1307:1316	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	10	14	theme	HCV	1480:1482	arg1	morphogenesis					1484:1496	HCV morphogenesis	1480:1496	HCV morphogenesis	1480:1496	In addition to its effect on HCV morphogenesis, OGT may play a role in HCV-induced liver disease and hepatocarcinogenesis.
31076402	4	15	theme	two-step	655:662	arg1	screen					703:708	a two-step functional high-throughput miRNA mimic screen	653:708	a two-step functional high-throughput miRNA mimic screen	653:708	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	1	16	theme	OBJECTIVE	154:162	arg1	process					241:247	a multistep process	229:247	a multistep process involving both viral and host factors	229:285	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	1	16	theme	OBJECTIVE	154:162	arg1	Infection					164:172	OBJECTIVE Infection	154:172	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV)	154:224	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	8	17	theme	OGT	1202:1204	arg1	expression					1206:1215	increased OGT expression	1192:1215	increased OGT expression in patient-derived liver tissue	1192:1247	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	3	18	theme	functional	500:509	arg1	role					526:529	the functional and regulatory role	496:529	the functional and regulatory role of miRNAs for the HCV life cycle	496:562	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	5	19	theme	functional	855:864	arg1	approaches					866:875	computational and functional approaches	837:875	computational and functional approaches	837:875	miRNA targeting was then assessed using a combination of computational and functional approaches.
31076402	4	20	theme	life	628:631	arg1	cycle					633:637	the HCV life cycle	620:637	the HCV life cycle	620:637	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	0	21	theme	virus	117:121	arg1	morphogenesis					123:135	hepatitis C virus morphogenesis	105:135	hepatitis C virus morphogenesis	105:135	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	7	22	theme	infectivity	1166:1176	arg1	regulators					1130:1139	regulators	1130:1139	regulators of HCV morphogenesis and infectivity	1130:1176	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	22	theme	infectivity	1166:1176	arg1	O-GlcNAcylation					1111:1125	O-GlcNAcylation	1111:1125	O-GlcNAcylation	1111:1125	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	22	theme	infectivity	1166:1176	arg1	OGT					1103:1105	OGT	1103:1105	OGT	1103:1105	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	4	23	theme	recombinant	742:752	arg1	HCV					775:777	recombinant cell culture-derived HCV	742:777	recombinant cell culture-derived HCV	742:777	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	4	24	theme	HCV	624:626	arg1	cycle					633:637	the HCV life cycle	620:637	the HCV life cycle	620:637	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	0	25	theme	microRNA	11:18	arg1	screen					20:25	Functional microRNA screen	0:25	Functional microRNA screen	0:25	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	10	26	dep	effect	1470:1475	arg1	addition					1454:1461	addition	1454:1461	addition	1454:1461	In addition to its effect on HCV morphogenesis, OGT may play a role in HCV-induced liver disease and hepatocarcinogenesis.
31076402	1	27	theme	hepatitis	202:210	arg1	HCV					221:223	HCV	221:223	HCV	221:223	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	1	27	theme	hepatitis	202:210	arg1	virus					214:218	the hepatitis C virus	198:218	the hepatitis C virus (HCV)	198:224	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	0	28	theme	Functional	0:9	arg1	screen					20:25	Functional microRNA screen	0:25	Functional microRNA screen	0:25	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	9	29	theme	undiscovered	1380:1391	arg1	OGT					1361:1363	their target OGT	1348:1363	their target OGT	1348:1363	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	29	theme	undiscovered	1380:1391	arg1	factors					1409:1415	previously undiscovered regulatory host factors	1369:1415	previously undiscovered regulatory host factors for HCV assembly and infectivity	1369:1448	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	29	theme	undiscovered	1380:1391	arg1	CONCLUSION					1307:1316	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	4	30	theme	miRNA	691:695	arg1	screen					703:708	a two-step functional high-throughput miRNA mimic screen	653:708	a two-step functional high-throughput miRNA mimic screen	653:708	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	5	31	theme	computational	837:849	arg1	approaches					866:875	computational and functional approaches	837:875	computational and functional approaches	837:875	miRNA targeting was then assessed using a combination of computational and functional approaches.
31076402	1	32	theme	C	212:212	arg1	HCV					221:223	HCV	221:223	HCV	221:223	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	1	32	theme	C	212:212	arg1	virus					214:218	the hepatitis C virus	198:218	the hepatitis C virus (HCV)	198:224	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	8	33	theme	liver	1236:1240	arg1	tissue					1242:1247	patient-derived liver tissue	1220:1247	patient-derived liver tissue	1220:1247	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	8	34	theme	increased	1192:1200	arg1	expression					1206:1215	increased OGT expression	1192:1215	increased OGT expression in patient-derived liver tissue	1192:1247	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	0	35	link	O-linked	36:43	arg1	factor					87:92	a host factor	80:92	a host factor modulating hepatitis C virus morphogenesis and infectivity	80:151	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	0	35	link	O-linked	36:43	arg1	transferase					65:75	O-linked N-acetylglucosamine transferase	36:75	O-linked N-acetylglucosamine transferase	36:75	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	8	36	theme	patient-derived	1220:1234	arg1	tissue					1242:1247	patient-derived liver tissue	1220:1247	patient-derived liver tissue	1220:1247	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	9	37	theme	host	1404:1407	arg1	OGT					1361:1363	their target OGT	1348:1363	their target OGT	1348:1363	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	37	theme	host	1404:1407	arg1	factors					1409:1415	previously undiscovered regulatory host factors	1369:1415	previously undiscovered regulatory host factors for HCV assembly and infectivity	1369:1448	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	37	theme	host	1404:1407	arg1	CONCLUSION					1307:1316	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	4	38	theme	cell	754:757	arg1	HCV					775:777	recombinant cell culture-derived HCV	742:777	recombinant cell culture-derived HCV	742:777	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	8	39	from	expression	1206:1215	arg1	tissue					1242:1247	patient-derived liver tissue	1220:1247	patient-derived liver tissue	1220:1247	Furthermore, increased OGT expression in patient-derived liver tissue was associated with HCV-induced liver disease and cancer.
31076402	3	40	theme	miRNAs	534:539	arg1	role					526:529	the functional and regulatory role	496:529	the functional and regulatory role of miRNAs for the HCV life cycle	496:562	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	4	41	theme	human	597:601	arg1	miRNAs					603:608	human miRNAs	597:608	human miRNAs affecting the HCV life cycle	597:637	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	0	42	theme	N-acetylglucosamine	45:63	arg1	factor					87:92	a host factor	80:92	a host factor modulating hepatitis C virus morphogenesis and infectivity	80:151	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	0	42	theme	N-acetylglucosamine	45:63	arg1	transferase					65:75	O-linked N-acetylglucosamine transferase	36:75	O-linked N-acetylglucosamine transferase	36:75	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	6	43	theme	assembly/release	952:967	arg1	miR-619-3p					914:923	miR-619-3p	914:923	miR-619-3p	914:923	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	6	43	theme	assembly/release	952:967	arg1	modulators					934:943	novel modulators	928:943	novel modulators of HCV assembly/release	928:967	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	6	43	theme	assembly/release	952:967	arg1	miR-501-3p					899:908	miR-501-3p	899:908	miR-501-3p	899:908	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	10	44	theme	HCV-induced	1522:1532	arg1	disease					1540:1546	HCV-induced liver disease	1522:1546	HCV-induced liver disease	1522:1546	In addition to its effect on HCV morphogenesis, OGT may play a role in HCV-induced liver disease and hepatocarcinogenesis.
31076402	5	45	theme	approaches	866:875	arg1	combination					822:832	a combination	820:832	a combination of computational and functional approaches	820:875	miRNA targeting was then assessed using a combination of computational and functional approaches.
31076402	0	46	theme	O-linked	36:43	arg1	factor					87:92	a host factor	80:92	a host factor modulating hepatitis C virus morphogenesis and infectivity	80:151	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	0	46	theme	O-linked	36:43	arg1	transferase					65:75	O-linked N-acetylglucosamine transferase	36:75	O-linked N-acetylglucosamine transferase	36:75	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	6	47	theme	HCV	948:950	arg1	assembly/release					952:967	HCV assembly/release	948:967	HCV assembly/release	948:967	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	7	48	theme	protein	1069:1075	arg1	expression					1077:1086	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	4	49	link	culture-derived	759:773	arg1	HCV					775:777	recombinant cell culture-derived HCV	742:777	recombinant cell culture-derived HCV	742:777	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	7	50	theme	morphogenesis	1148:1160	arg1	regulators					1130:1139	regulators	1130:1139	regulators of HCV morphogenesis and infectivity	1130:1176	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	50	theme	morphogenesis	1148:1160	arg1	O-GlcNAcylation					1111:1125	O-GlcNAcylation	1111:1125	O-GlcNAcylation	1111:1125	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	50	theme	morphogenesis	1148:1160	arg1	OGT					1103:1105	OGT	1103:1105	OGT	1103:1105	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	51	link	O-linked	1011:1018	arg1	OGT					1064:1066	OGT	1064:1066	OGT	1064:1066	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	51	link	O-linked	1011:1018	arg1	transferase					1051:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase	1011:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	9	52	theme	regulatory	1393:1402	arg1	OGT					1361:1363	their target OGT	1348:1363	their target OGT	1348:1363	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	52	theme	regulatory	1393:1402	arg1	factors					1409:1415	previously undiscovered regulatory host factors	1369:1415	previously undiscovered regulatory host factors for HCV assembly and infectivity	1369:1448	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	9	52	theme	regulatory	1393:1402	arg1	CONCLUSION					1307:1316	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p	1307:1342	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31076402	3	53	theme	HCV	549:551	arg1	cycle					558:562	the HCV life cycle	545:562	the HCV life cycle	545:562	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	7	54	theme	O-GlcNAc	1041:1048	arg1	OGT					1064:1066	OGT	1064:1066	OGT	1064:1066	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	54	theme	O-GlcNAc	1041:1048	arg1	transferase					1051:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase	1011:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	4	55	theme	high-throughput	675:689	arg1	screen					703:708	a two-step functional high-throughput miRNA mimic screen	653:708	a two-step functional high-throughput miRNA mimic screen	653:708	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	5	56	theme	miRNA	780:784	arg1	targeting					786:794	miRNA targeting	780:794	miRNA targeting	780:794	miRNA targeting was then assessed using a combination of computational and functional approaches.
31076402	3	57	theme	life	553:556	arg1	cycle					558:562	the HCV life cycle	545:562	the HCV life cycle	545:562	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	7	58	theme	O-linked	1011:1018	arg1	OGT					1064:1066	OGT	1064:1066	OGT	1064:1066	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	58	theme	O-linked	1011:1018	arg1	transferase					1051:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase	1011:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	4	59	theme	functional	664:673	arg1	screen					703:708	a two-step functional high-throughput miRNA mimic screen	653:708	a two-step functional high-throughput miRNA mimic screen	653:708	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	6	60	theme	novel	928:932	arg1	miR-619-3p					914:923	miR-619-3p	914:923	miR-619-3p	914:923	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	6	60	theme	novel	928:932	arg1	modulators					934:943	novel modulators	928:943	novel modulators of HCV assembly/release	928:967	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	6	60	theme	novel	928:932	arg1	miR-501-3p					899:908	miR-501-3p	899:908	miR-501-3p	899:908	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	7	61	theme	N-acetylglucosamine	1020:1038	arg1	OGT					1064:1066	OGT	1064:1066	OGT	1064:1066	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	7	61	theme	N-acetylglucosamine	1020:1038	arg1	transferase					1051:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase	1011:1061	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	2	62	theme	non-coding	317:326	arg1	RNAs					328:331	small non-coding RNAs	311:331	small non-coding RNAs that post-transcriptionally regulate gene expression	311:384	microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression.
31076402	2	62	theme	non-coding	317:326	arg1	microRNAs					288:296	microRNAs	288:296	microRNAs (miRNAs)	288:305	microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression.
31076402	6	63	dep	RESULTS	878:884	arg1	We					886:887	We	886:887	We	886:887	RESULTS We uncovered miR-501-3p and miR-619-3p as novel modulators of HCV assembly/release.
31076402	7	64	theme	transferase	1051:1061	arg1	expression					1077:1086	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression	1011:1086	We discovered that these miRNAs regulate O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) protein expression and identified OGT and O-GlcNAcylation as regulators of HCV morphogenesis and infectivity.
31076402	4	65	theme	culture-derived	759:773	arg1	HCV					775:777	recombinant cell culture-derived HCV	742:777	recombinant cell culture-derived HCV	742:777	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	2	66	theme	small	311:315	arg1	RNAs					328:331	small non-coding RNAs	311:331	small non-coding RNAs that post-transcriptionally regulate gene expression	311:384	microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression.
31076402	2	66	theme	small	311:315	arg1	microRNAs					288:296	microRNAs	288:296	microRNAs (miRNAs)	288:305	microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression.
31076402	3	67	theme	human	459:463	arg1	genes					465:469	all human genes	455:469	all human genes	455:469	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	0	68	theme	host	82:85	arg1	factor					87:92	a host factor	80:92	a host factor modulating hepatitis C virus morphogenesis and infectivity	80:151	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	0	68	theme	host	82:85	arg1	transferase					65:75	O-linked N-acetylglucosamine transferase	36:75	O-linked N-acetylglucosamine transferase	36:75	Functional microRNA screen uncovers O-linked N-acetylglucosamine transferase as a host factor modulating hepatitis C virus morphogenesis and infectivity.
31076402	1	69	dep	both	259:262	arg1	viral					264:268	viral	264:268	viral	264:268	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	10	70	from	effect	1470:1475	arg1	morphogenesis					1484:1496	HCV morphogenesis	1480:1496	HCV morphogenesis	1480:1496	In addition to its effect on HCV morphogenesis, OGT may play a role in HCV-induced liver disease and hepatocarcinogenesis.
31076402	3	71	theme	genes	465:469	arg1	%					442:442	30%	440:442	30%	440:442	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	3	71	theme	genes	465:469	arg1	%					450:450	75%	448:450	75% of all human genes	448:469	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	3	71	theme	genes	465:469	arg1	genes					465:469	all human genes	455:469	all human genes	455:469	Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle.
31076402	1	72	theme	multistep	231:239	arg1	process					241:247	a multistep process	229:247	a multistep process involving both viral and host factors	229:285	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	1	72	theme	multistep	231:239	arg1	Infection					164:172	OBJECTIVE Infection	154:172	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV)	154:224	OBJECTIVE Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors.
31076402	4	73	dep	screen	703:708	arg1	mimic					697:701	mimic	697:701	mimic	697:701	DESIGN To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7.5.1 cells infected with recombinant cell culture-derived HCV.
31076402	2	74	theme	gene	370:373	arg1	expression					375:384	gene expression	370:384	gene expression	370:384	microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression.
31076402	9	75	theme	HCV	1421:1423	arg1	assembly					1425:1432	HCV assembly	1421:1432	HCV assembly	1421:1432	CONCLUSION miR-501-3p and miR-619-3p and their target OGT are previously undiscovered regulatory host factors for HCV assembly and infectivity.
31862392	12	0	theme	virulence	1796:1804	arg1	protease					1836:1843	protease	1836:1843	protease	1836:1843	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	0	theme	virulence	1796:1804	arg1	factors					1806:1812	virulence factors	1796:1812	virulence factors	1796:1812	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	0	theme	virulence	1796:1804	arg1	elastase					1846:1853	elastase	1846:1853	elastase	1846:1853	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	0	theme	virulence	1796:1804	arg1	polysaccharides					1888:1902	extracellular polysaccharides	1874:1902	extracellular polysaccharides of P. aeruginosa PAO1	1874:1924	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	0	theme	virulence	1796:1804	arg1	pyocyanin					1825:1833	pyocyanin	1825:1833	pyocyanin	1825:1833	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	0	theme	virulence	1796:1804	arg1	rhamnolipids					1856:1867	rhamnolipids	1856:1867	rhamnolipids	1856:1867	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	5	1	theme	formation	618:626	arg1	pathogen					728:735	an opportunistic multidrug resistance pathogen	690:735	an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents	690:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	5	1	theme	formation	618:626	arg1	phenomenon					647:656	biofilm formation and quorum sensing phenomenon	610:656	biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1	610:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	11	2	theme	significant	1615:1625	arg1	activity					1647:1654	significant anti-quorum sensing activity	1615:1654	significant anti-quorum sensing activity	1615:1654	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	9	3	theme	virulence	1384:1392	arg1	factors					1394:1400	virulence factors	1384:1400	virulence factors	1384:1400	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	5	4	theme	biofilm	610:616	arg1	formation					618:626	biofilm formation	610:626	biofilm formation	610:626	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	13	5	theme	biofilm	1987:1993	arg1	formation					1995:2003	biofilm formation	1987:2003	biofilm formation of P. aeruginosa PAO1	1987:2025	The MELE also disturbed biofilm formation of P. aeruginosa PAO1.
31862392	2	6	theme	mycobiont	265:273	arg1	microfungi					298:307	the mycobiont, numerous non-obligate microfungi	261:307	the mycobiont, numerous non-obligate microfungi live in lichen thalli	261:329	Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli.
31862392	2	7	from	thalli	324:329	arg1	live					309:312	live	309:312	live	309:312	Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli.
31862392	8	8	theme	Chromobacterium	1204:1218	arg1	violaceum					1220:1228	the biomarker strain Chromobacterium violaceum 12472	1183:1234	the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling	1183:1312	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	10	9	theme	%	1535:1535	arg1	similarity					1537:1546	100% similarity	1532:1546	100% similarity with Aspergillus quandricinctus strain CBS 135.52	1532:1596	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	12	10	theme	extracellular	1874:1886	arg1	polysaccharides					1888:1902	extracellular polysaccharides	1874:1902	extracellular polysaccharides of P. aeruginosa PAO1	1874:1924	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	16	11	contain	possesses	2372:2380	arg2	potential					2382:2390	potential	2382:2390	potential to inhibit quorum sensing and biofilm formation of P. aeruginosa	2382:2455	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	16	11	contain	possesses	2372:2380	arg1	quandricinctus					2357:2370	quandricinctus	2357:2370	quandricinctus	2357:2370	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	10	12	theme	CBS	1587:1589	arg1	135.52					1591:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	9	13	theme	P.	1427:1428	arg1	PAO1					1441:1444	P. aeruginosa PAO1	1427:1444	P. aeruginosa PAO1	1427:1444	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	8	14	theme	sensing	1160:1166	arg1	activity					1168:1175	anti-quorum sensing activity	1148:1175	anti-quorum sensing activity	1148:1175	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	7	15	theme	fungal	1038:1043	arg1	genome					1045:1050	the fungal genome	1034:1050	the fungal genome	1034:1050	The isolated ELF was identified by amplifying the long subunit region of the fungal genome.
31862392	11	16	dep	P.	1738:1739	arg1	aeruginosa					1741:1750	aeruginosa	1741:1750	aeruginosa	1741:1750	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	9	17	theme	PAO1	1441:1444	arg1	production					1370:1379	the production	1366:1379	the production of virulence factors	1366:1400	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	9	17	theme	PAO1	1441:1444	arg1	formation					1414:1422	biofilm formation	1406:1422	biofilm formation of P. aeruginosa PAO1	1406:1444	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	6	18	theme	alternative	911:921	arg1	approach					923:930	the paramount alternative approach	897:930	the paramount alternative approach to conventional antibiotics	897:958	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	6	18	theme	alternative	911:921	arg1	sensing					841:847	inhibiting quorum sensing	823:847	inhibiting quorum sensing to manage the infection caused by PAO1	823:886	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	5	19	from	PAO1	684:687	arg1	control					599:605	control	599:605	control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents	599:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	8	20	theme	biomarker	1187:1195	arg1	violaceum					1220:1228	the biomarker strain Chromobacterium violaceum 12472	1183:1234	the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling	1183:1312	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	7	21	theme	subunit	1016:1022	arg1	region					1024:1029	the long subunit region	1007:1029	the long subunit region of the fungal genome	1007:1050	The isolated ELF was identified by amplifying the long subunit region of the fungal genome.
31862392	8	22	theme	mediated	1279:1286	arg1	quorum					1288:1293	the AHL mediated quorum	1271:1293	the AHL mediated quorum sensing signalling	1271:1312	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	11	23	theme	PAO1	1752:1755	arg1	viability					1725:1733	the bacterial cell viability	1706:1733	the bacterial cell viability of P. aeruginosa PAO1	1706:1755	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	5	24	theme	sensing	639:645	arg1	pathogen					728:735	an opportunistic multidrug resistance pathogen	690:735	an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents	690:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	5	24	theme	sensing	639:645	arg1	phenomenon					647:656	biofilm formation and quorum sensing phenomenon	610:656	biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1	610:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	5	25	dep	Pseudomonas	661:671	arg1	aeruginosa					673:682	aeruginosa	673:682	aeruginosa	673:682	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	11	26	theme	P.	1738:1739	arg1	PAO1					1752:1755	P. aeruginosa PAO1	1738:1755	P. aeruginosa PAO1	1738:1755	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	5	27	from	phenomenon	647:656	arg1	PAO1					684:687	Pseudomonas aeruginosa PAO1	661:687	Pseudomonas aeruginosa PAO1	661:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	1	28	theme	composite	158:166	arg1	Lichens					146:152	Lichens	146:152	Lichens	146:152	Lichens are composite organisms, comprising of a fungus (mycobiont) and a blue-green alga (photobiont).
31862392	1	28	theme	composite	158:166	arg1	organisms					168:176	composite organisms	158:176	composite organisms	158:176	Lichens are composite organisms, comprising of a fungus (mycobiont) and a blue-green alga (photobiont).
31862392	12	29	theme	PAO1	1921:1924	arg1	elastase					1846:1853	elastase	1846:1853	elastase	1846:1853	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	29	theme	PAO1	1921:1924	arg1	protease					1836:1843	protease	1836:1843	protease	1836:1843	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	29	theme	PAO1	1921:1924	arg1	pyocyanin					1825:1833	pyocyanin	1825:1833	pyocyanin	1825:1833	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	29	theme	PAO1	1921:1924	arg1	polysaccharides					1888:1902	extracellular polysaccharides	1874:1902	extracellular polysaccharides of P. aeruginosa PAO1	1874:1924	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	12	29	theme	PAO1	1921:1924	arg1	rhamnolipids					1856:1867	rhamnolipids	1856:1867	rhamnolipids	1856:1867	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	2	30	from	live	309:312	arg1	thalli					324:329	lichen thalli	317:329	lichen thalli	317:329	Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli.
31862392	16	31	theme	first	2329:2333	arg1	time					2335:2338	first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities	2329:2523	first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities	2329:2523	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	0	32	theme	biofilm	96:102	arg1	formation					104:112	biofilm formation	96:112	biofilm formation	96:112	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	16	33	dep	quandricinctus	2357:2370	arg1	A.					2354:2355	A.	2354:2355	A.	2354:2355	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	14	34	theme	3-D	2032:2034	arg1	analysis					2036:2043	The 3-D analysis	2028:2043	The 3-D analysis of biofilm architecture	2028:2067	The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased.
31862392	4	35	theme	natural	437:443	arg1	sources					445:451	promising natural sources	427:451	promising natural sources because of their capability to exert unique drug molecules	427:510	In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules.
31862392	5	36	theme	opportunistic	693:705	arg1	pathogen					728:735	an opportunistic multidrug resistance pathogen	690:735	an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents	690:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	5	36	theme	opportunistic	693:705	arg1	phenomenon					647:656	biofilm formation and quorum sensing phenomenon	610:656	biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1	610:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	0	37	theme	quorum	77:82	arg1	sensing					84:90	quorum sensing	77:90	quorum sensing	77:90	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	0	38	theme	Endolichenic	0:11	arg1	quandricinctus					33:46	Endolichenic fungus, Aspergillus quandricinctus	0:46	quandricinctus	33:46	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	12	39	theme	P.	1907:1908	arg1	PAO1					1921:1924	P. aeruginosa PAO1	1907:1924	P. aeruginosa PAO1	1907:1924	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	3	40	theme	endolichenic	360:371	arg1	ELF					380:382	ELF	380:382	ELF	380:382	These microfungi are called endolichenic fungi (ELF).
31862392	3	40	theme	endolichenic	360:371	arg1	fungi					373:377	endolichenic fungi	360:377	endolichenic fungi (ELF)	360:383	These microfungi are called endolichenic fungi (ELF).
31862392	15	41	theme	major	2271:2275	arg1	acids					2261:2265	fatty acids	2255:2265	fatty acids	2255:2265	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	41	theme	major	2271:2275	arg1	constituents					2277:2288	major constituents	2271:2288	major constituents of the MELE	2271:2300	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	41	theme	major	2271:2275	arg1	acids					2245:2249	organic acids	2237:2249	organic acids	2237:2249	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	6	42	theme	quorum	834:839	arg1	approach					923:930	the paramount alternative approach	897:930	the paramount alternative approach to conventional antibiotics	897:958	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	6	42	theme	quorum	834:839	arg1	sensing					841:847	inhibiting quorum sensing	823:847	inhibiting quorum sensing to manage the infection caused by PAO1	823:886	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	5	43	theme	quorum	747:752	arg1	sensing					754:760	quorum sensing	747:760	quorum sensing network	747:768	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	4	44	theme	unique	490:495	arg1	molecules					502:510	unique drug molecules	490:510	unique drug molecules	490:510	In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules.
31862392	5	45	theme	resistance	717:726	arg1	pathogen					728:735	an opportunistic multidrug resistance pathogen	690:735	an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents	690:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	5	45	theme	resistance	717:726	arg1	phenomenon					647:656	biofilm formation and quorum sensing phenomenon	610:656	biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1	610:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	0	46	theme	Usnea	51:55	arg1	longissima					57:66	Usnea longissima	51:66	Usnea longissima	51:66	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	0	47	dep	quandricinctus	33:46	arg1	Aspergillus					21:31	Endolichenic fungus, Aspergillus quandricinctus	0:46	Aspergillus	21:31	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	14	48	theme	biofilm	2048:2054	arg1	architecture					2056:2067	biofilm architecture	2048:2067	biofilm architecture	2048:2067	The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased.
31862392	16	49	theme	quorum	2403:2408	arg1	sensing					2410:2416	quorum sensing	2403:2416	quorum sensing	2403:2416	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	2	50	theme	lichen	317:322	arg1	thalli					324:329	lichen thalli	317:329	lichen thalli	317:329	Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli.
31862392	8	51	theme	ELF	1082:1084	arg1	metabolites					1067:1077	The extracted metabolites	1053:1077	The extracted metabolites of ELF (MELE) using the acetone solvent	1053:1117	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	15	52	theme	MELE	2217:2220	arg1	analysis					2205:2212	The GC-MS analysis	2195:2212	The GC-MS analysis of MELE	2195:2220	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	6	53	dep	sensing	841:847	arg1	manage					852:857	manage	852:857	to manage the infection caused by PAO1	849:886	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	10	54	theme	100	1532:1534	arg1	%					1535:1535	%	1535:1535	%	1535:1535	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	11	55	theme	cell	1720:1723	arg1	viability					1725:1733	the bacterial cell viability	1706:1733	the bacterial cell viability of P. aeruginosa PAO1	1706:1755	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	13	56	theme	P.	2008:2009	arg1	PAO1					2022:2025	P. aeruginosa PAO1	2008:2025	P. aeruginosa PAO1	2008:2025	The MELE also disturbed biofilm formation of P. aeruginosa PAO1.
31862392	5	57	theme	sensing	754:760	arg1	network					762:768	quorum sensing network	747:768	quorum sensing network	747:768	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	16	58	theme	aeruginosa	2446:2455	arg1	sensing					2410:2416	quorum sensing	2403:2416	quorum sensing	2403:2416	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	16	58	theme	aeruginosa	2446:2455	arg1	formation					2430:2438	biofilm formation	2422:2438	biofilm formation	2422:2438	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	12	59	theme	factors	1806:1812	arg1	production					1782:1791	the production	1778:1791	the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner	1778:1960	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	13	60	theme	PAO1	2022:2025	arg1	formation					1995:2003	biofilm formation	1987:2003	biofilm formation of P. aeruginosa PAO1	1987:2025	The MELE also disturbed biofilm formation of P. aeruginosa PAO1.
31862392	12	61	from	production	1782:1791	arg1	manner					1955:1960	a concentration-dependent manner	1929:1960	a concentration-dependent manner	1929:1960	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	10	62	theme	Aspergillus	1553:1563	arg1	135.52					1591:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	11	63	theme	anti-quorum	1627:1637	arg1	activity					1647:1654	significant anti-quorum sensing activity	1615:1654	significant anti-quorum sensing activity	1615:1654	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	9	64	theme	factors	1394:1400	arg1	production					1370:1379	the production	1366:1379	the production of virulence factors	1366:1400	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	9	64	theme	factors	1394:1400	arg1	formation					1414:1422	biofilm formation	1406:1422	biofilm formation of P. aeruginosa PAO1	1406:1444	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	8	65	theme	acetone	1103:1109	arg1	solvent					1111:1117	the acetone solvent	1099:1117	the acetone solvent	1099:1117	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	4	66	theme	recent	389:394	arg1	years					396:400	recent years	389:400	recent years	389:400	In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules.
31862392	9	67	theme	biofilm	1406:1412	arg1	formation					1414:1422	biofilm formation	1406:1422	biofilm formation of P. aeruginosa PAO1	1406:1444	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	10	68	with	similarity	1537:1546	arg1	135.52					1591:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	12	69	dep	P.	1907:1908	arg1	aeruginosa					1910:1919	aeruginosa	1910:1919	aeruginosa	1910:1919	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	8	70	theme	strain	1197:1202	arg1	violaceum					1220:1228	the biomarker strain Chromobacterium violaceum 12472	1183:1234	the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling	1183:1312	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	7	71	theme	genome	1045:1050	arg1	region					1024:1029	the long subunit region	1007:1029	the long subunit region of the fungal genome	1007:1050	The isolated ELF was identified by amplifying the long subunit region of the fungal genome.
31862392	2	72	theme	live	309:312	arg1	microfungi					298:307	the mycobiont, numerous non-obligate microfungi	261:307	the mycobiont, numerous non-obligate microfungi live in lichen thalli	261:329	Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli.
31862392	14	73	theme	architecture	2056:2067	arg1	analysis					2036:2043	The 3-D analysis	2028:2043	The 3-D analysis of biofilm architecture	2028:2067	The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased.
31862392	6	74	theme	conventional	935:946	arg1	antibiotics					948:958	conventional antibiotics	935:958	conventional antibiotics	935:958	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	10	75	theme	strain	1580:1585	arg1	135.52					1591:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	Aspergillus quandricinctus strain CBS 135.52	1553:1596	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	0	76	theme	PAO1	140:143	arg1	sensing					84:90	quorum sensing	77:90	quorum sensing	77:90	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	0	76	theme	PAO1	140:143	arg1	formation					104:112	biofilm formation	96:112	biofilm formation	96:112	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	2	77	theme	non-obligate	285:296	arg1	microfungi					298:307	the mycobiont, numerous non-obligate microfungi	261:307	the mycobiont, numerous non-obligate microfungi live in lichen thalli	261:329	Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli.
31862392	8	78	theme	anti-quorum	1148:1158	arg1	activity					1168:1175	anti-quorum sensing activity	1148:1175	anti-quorum sensing activity	1148:1175	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	14	79	theme	MELE	2175:2178	arg1	concentration					2158:2170	the concentration	2154:2170	the concentration of MELE	2154:2178	The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased.
31862392	10	80	dep	Aspergillus	1553:1563	arg1	quandricinctus					1565:1578	quandricinctus	1565:1578	quandricinctus	1565:1578	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	5	81	theme	agents	804:809	arg1	array					784:788	an array	781:788	an array of pathogenic agents	781:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	6	82	theme	paramount	901:909	arg1	approach					923:930	the paramount alternative approach	897:930	the paramount alternative approach to conventional antibiotics	897:958	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	6	82	theme	paramount	901:909	arg1	sensing					841:847	inhibiting quorum sensing	823:847	inhibiting quorum sensing to manage the infection caused by PAO1	823:886	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	4	83	theme	promising	427:435	arg1	sources					445:451	promising natural sources	427:451	promising natural sources because of their capability to exert unique drug molecules	427:510	In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules.
31862392	8	84	theme	violacein	1249:1257	arg1	pigment					1259:1265	violacein pigment	1249:1265	violacein pigment	1249:1265	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	7	85	theme	long	1011:1014	arg1	region					1024:1029	the long subunit region	1007:1029	the long subunit region of the fungal genome	1007:1050	The isolated ELF was identified by amplifying the long subunit region of the fungal genome.
31862392	5	86	theme	current	517:523	arg1	study					525:529	The current study	513:529	The current study	513:529	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	15	87	theme	organic	2237:2243	arg1	acids					2261:2265	fatty acids	2255:2265	fatty acids	2255:2265	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	87	theme	organic	2237:2243	arg1	constituents					2277:2288	major constituents	2271:2288	major constituents of the MELE	2271:2300	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	87	theme	organic	2237:2243	arg1	acids					2245:2249	organic acids	2237:2249	organic acids	2237:2249	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	5	88	theme	phenomenon	647:656	arg1	control					599:605	control	599:605	control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents	599:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	5	89	theme	quorum	632:637	arg1	sensing					639:645	quorum sensing	632:645	quorum sensing	632:645	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	8	90	theme	AHL	1275:1277	arg1	quorum					1288:1293	the AHL mediated quorum	1271:1293	the AHL mediated quorum sensing signalling	1271:1312	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	16	91	theme	present	2307:2313	arg1	study					2315:2319	The present study	2303:2319	The present study	2303:2319	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	5	92	theme	multidrug	707:715	arg1	pathogen					728:735	an opportunistic multidrug resistance pathogen	690:735	an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents	690:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	5	92	theme	multidrug	707:715	arg1	phenomenon					647:656	biofilm formation and quorum sensing phenomenon	610:656	biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1	610:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	7	93	theme	isolated	965:972	arg1	ELF					974:976	The isolated ELF	961:976	The isolated ELF	961:976	The isolated ELF was identified by amplifying the long subunit region of the fungal genome.
31862392	4	94	theme	capability	470:479	arg1	sources					445:451	promising natural sources	427:451	promising natural sources because of their capability to exert unique drug molecules	427:510	In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules.
31862392	15	95	theme	GC-MS	2199:2203	arg1	analysis					2205:2212	The GC-MS analysis	2195:2212	The GC-MS analysis of MELE	2195:2220	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	2	96	dep	mycobiont	265:273	arg1	numerous					276:283	numerous	276:283	numerous	276:283	Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli.
31862392	12	97	theme	concentration-dependent	1931:1953	arg1	manner					1955:1960	a concentration-dependent manner	1929:1960	a concentration-dependent manner	1929:1960	The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner.
31862392	0	98	dep	Pseudomonas	117:127	arg1	aeruginosa					129:138	aeruginosa	129:138	aeruginosa	129:138	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	0	99	theme	Pseudomonas	117:127	arg1	PAO1					140:143	Pseudomonas aeruginosa PAO1	117:143	Pseudomonas aeruginosa PAO1	117:143	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	5	100	theme	pathogenic	793:802	arg1	agents					804:809	pathogenic agents	793:809	pathogenic agents	793:809	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	0	101	theme	fungus	13:18	arg1	quandricinctus					33:46	Endolichenic fungus, Aspergillus quandricinctus	0:46	quandricinctus	33:46	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	15	102	theme	fatty	2255:2259	arg1	acids					2261:2265	fatty acids	2255:2265	fatty acids	2255:2265	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	102	theme	fatty	2255:2259	arg1	constituents					2277:2288	major constituents	2271:2288	major constituents of the MELE	2271:2300	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	102	theme	fatty	2255:2259	arg1	acids					2245:2249	organic acids	2237:2249	organic acids	2237:2249	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	5	103	theme	Pseudomonas	661:671	arg1	PAO1					684:687	Pseudomonas aeruginosa PAO1	661:687	Pseudomonas aeruginosa PAO1	661:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	14	104	theme	surface	2099:2105	arg1	area					2107:2110	the thickness and surface area	2081:2110	area	2107:2110	The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased.
31862392	14	105	theme	thickness	2085:2093	arg1	area					2107:2110	the thickness and surface area	2081:2110	area	2107:2110	The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased.
31862392	8	106	theme	extracted	1057:1065	arg1	metabolites					1067:1077	The extracted metabolites	1053:1077	The extracted metabolites of ELF (MELE) using the acetone solvent	1053:1117	The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling.
31862392	6	107	theme	inhibiting	823:832	arg1	approach					923:930	the paramount alternative approach	897:930	the paramount alternative approach to conventional antibiotics	897:958	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	6	107	theme	inhibiting	823:832	arg1	sensing					841:847	inhibiting quorum sensing	823:847	inhibiting quorum sensing to manage the infection caused by PAO1	823:886	Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics.
31862392	13	108	dep	P.	2008:2009	arg1	aeruginosa					2011:2020	aeruginosa	2011:2020	aeruginosa	2011:2020	The MELE also disturbed biofilm formation of P. aeruginosa PAO1.
31862392	4	109	theme	drug	497:500	arg1	molecules					502:510	unique drug molecules	490:510	unique drug molecules	490:510	In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules.
31862392	10	110	theme	molecular	1451:1459	arg1	identification					1461:1474	The molecular identification	1447:1474	The molecular identification	1447:1474	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	11	111	theme	4 mg/mL	1680:1686	arg1	concentration					1663:1675	the concentration	1659:1675	the concentration of 4 mg/mL	1659:1686	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	9	112	dep	P.	1427:1428	arg1	aeruginosa					1430:1439	aeruginosa	1430:1439	aeruginosa	1430:1439	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	0	113	theme	longissima	57:66	arg1	quandricinctus					33:46	Endolichenic fungus, Aspergillus quandricinctus	0:46	quandricinctus	33:46	Endolichenic fungus, Aspergillus quandricinctus of Usnea longissima inhibits quorum sensing and biofilm formation of Pseudomonas aeruginosa PAO1.
31862392	9	114	theme	MELE	1339:1342	arg1	effect					1329:1334	the effect	1325:1334	the effect of MELE	1325:1342	Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1.
31862392	16	115	theme	healthcare	2503:2512	arg1	facilities					2514:2523	healthcare facilities	2503:2523	healthcare facilities	2503:2523	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	10	116	theme	accession	1495:1503	arg1	ELF					1490:1492	ELF	1490:1492	ELF (accession number MN171299)	1490:1520	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	10	116	theme	accession	1495:1503	arg1	number					1505:1510	accession number MN171299	1495:1519	accession number MN171299	1495:1519	The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52.
31862392	5	117	from	control	599:605	arg1	PAO1					684:687	Pseudomonas aeruginosa PAO1	661:687	Pseudomonas aeruginosa PAO1	661:687	The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents.
31862392	15	118	theme	MELE	2297:2300	arg1	acids					2261:2265	fatty acids	2255:2265	fatty acids	2255:2265	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	118	theme	MELE	2297:2300	arg1	constituents					2277:2288	major constituents	2271:2288	major constituents of the MELE	2271:2300	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	15	118	theme	MELE	2297:2300	arg1	acids					2245:2249	organic acids	2237:2249	organic acids	2237:2249	The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE.
31862392	11	119	theme	bacterial	1710:1718	arg1	viability					1725:1733	the bacterial cell viability	1706:1733	the bacterial cell viability of P. aeruginosa PAO1	1706:1755	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
31862392	16	120	theme	biofilm	2422:2428	arg1	formation					2430:2438	biofilm formation	2422:2438	biofilm formation	2422:2438	The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.
31862392	1	121	theme	blue-green	220:229	arg1	alga					231:234	a blue-green alga	218:234	a blue-green alga (photobiont)	218:247	Lichens are composite organisms, comprising of a fungus (mycobiont) and a blue-green alga (photobiont).
31862392	1	121	theme	blue-green	220:229	arg1	photobiont					237:246	photobiont	237:246	photobiont	237:246	Lichens are composite organisms, comprising of a fungus (mycobiont) and a blue-green alga (photobiont).
31862392	11	122	theme	sensing	1639:1645	arg1	activity					1647:1654	significant anti-quorum sensing activity	1615:1654	significant anti-quorum sensing activity	1615:1654	The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1.
29622561	4	0	theme	muscle	934:939	arg1	cells					941:945	cultured rat vascular smooth muscle cells	905:945	cultured rat vascular smooth muscle cells	905:945	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	9	1	theme	inflammatory	2067:2078	arg1	response					2080:2087	inflammatory response	2067:2087	inflammatory response	2067:2087	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	3	2	theme	TNFAIP3	723:729	arg1	factor					747:752	TNFAIP3 [tumor necrosis factor	723:752	TNFAIP3 [tumor necrosis factor α-induced protein 3	723:772	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	1	3	theme	NF-κB	474:478	arg1	signaling					500:508	NF-κB (nuclear factor-κB) signaling	474:508	NF-κB (nuclear factor-κB) signaling	474:508	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	8	4	theme	glucosamine	1833:1843	arg1	treatment					1845:1853	glucosamine treatment	1833:1853	glucosamine treatment	1833:1853	In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment.
29622561	1	5	theme	O-linked	284:291	arg1	levels					326:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	7	6	theme	proinflammatory	1573:1587	arg1	expression					1598:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	7	7	theme	inhibitory	1524:1533	arg1	effects					1535:1541	the inhibitory effects	1520:1541	the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation	1520:1667	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	6	8	theme	tumor	1364:1368	arg1	factor-α					1379:1386	tumor necrosis factor-α	1364:1386	tumor necrosis factor-α	1364:1386	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	1	9	theme	nuclear	481:487	arg1	factor-κB					489:497	nuclear factor-κB	481:497	nuclear factor-κB	481:497	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	4	10	theme	cultured	905:912	arg1	cells					941:945	cultured rat vascular smooth muscle cells	905:945	cultured rat vascular smooth muscle cells	905:945	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	10	11	theme	signaling	2298:2306	arg1	cascades					2308:2315	NF-κB signaling cascades	2292:2315	NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture	2292:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	6	12	theme	Adenovirus-mediated	1259:1277	arg1	overexpression					1283:1296	Adenovirus-mediated A20 overexpression	1259:1296	Adenovirus-mediated A20 overexpression	1259:1296	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	9	13	theme	scramble	2103:2110	arg1	shRNA					2112:2116	scramble shRNA	2103:2116	scramble shRNA	2103:2116	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	3	14	theme	α-induced	754:762	arg1	protein					764:770	α-induced protein 3	754:772	TNFAIP3 [tumor necrosis factor α-induced protein 3	723:772	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	8	15	theme	neointimal	1874:1883	arg1	formation					1885:1893	neointimal formation	1874:1893	neointimal formation	1874:1893	In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment.
29622561	6	16	dep	IκB	1397:1399	arg1	inhibitor					1402:1410	inhibitor	1402:1410	inhibitor of κB	1402:1416	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	7	17	theme	thiamet	1546:1552	arg1	G					1554:1554	thiamet G	1546:1554	thiamet G	1546:1554	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	4	18	theme	vascular	918:925	arg1	cells					941:945	cultured rat vascular smooth muscle cells	905:945	cultured rat vascular smooth muscle cells	905:945	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	7	19	theme	A20	1492:1494	arg1	overexpression					1496:1509	A20 overexpression	1492:1509	A20 overexpression	1492:1509	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	2	20	theme	glucosamine-induced	594:612	arg1	protection					623:632	glucosamine-induced vascular protection	594:632	glucosamine-induced vascular protection	594:632	However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear.
29622561	1	21	theme	rat	426:428	arg1	model					430:434	a rat model	424:434	a rat model of carotid injury	424:452	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	4	22	theme	inhibitor	1016:1024	arg1	APPROACH					881:888	APPROACH	881:888	APPROACH	881:888	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	4	22	theme	inhibitor	1016:1024	arg1	G					1034:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	9	23	theme	vascular	2147:2154	arg1	protection					2156:2165	the vascular protection	2143:2165	the vascular protection of glucosamine	2143:2180	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	6	24	from	prevention	1343:1352	arg1	activity					1482:1489	DNA-binding activity	1470:1489	DNA-binding activity	1470:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	4	25	from	RESULTS	894:900	arg1	cells					941:945	cultured rat vascular smooth muscle cells	905:945	cultured rat vascular smooth muscle cells	905:945	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	6	26	theme	thiamet	1330:1336	arg1	G					1338:1338	thiamet G	1330:1338	thiamet G	1330:1338	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	0	27	theme	Acute	153:157	arg1	Injury					180:185	Acute Endoluminal Arterial Injury	153:185	Acute Endoluminal Arterial Injury	153:185	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	1	28	theme	injury	447:452	arg1	model					430:434	a rat model	424:434	a rat model of carotid injury	424:452	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	4	29	from	APPROACH	881:888	arg1	cells					941:945	cultured rat vascular smooth muscle cells	905:945	cultured rat vascular smooth muscle cells	905:945	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	6	30	theme	necrosis	1370:1377	arg1	factor-α					1379:1386	tumor necrosis factor-α	1364:1386	tumor necrosis factor-α	1364:1386	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	7	31	theme	A20	1731:1733	arg1	shRNA					1735:1739	specific A20 shRNA	1722:1739	specific A20 shRNA	1722:1739	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	3	32	theme	vascular	860:867	arg1	protection					869:878	vascular protection	860:878	vascular protection	860:878	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	6	33	theme	-induced	1388:1395	arg1	degradation					1419:1429	TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation	1357:1429	TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation	1357:1429	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	1	34	dep	NF-κB	474:478	arg1	factor-κB					489:497	nuclear factor-κB	481:497	nuclear factor-κB	481:497	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	2	35	theme	molecular	533:541	arg1	responsible					578:588	responsible	578:588	responsible	578:588	However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear.
29622561	2	35	theme	molecular	533:541	arg1	target					543:548	the specific molecular target	520:548	the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection	520:632	However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear.
29622561	4	36	theme	O-linked	983:990	arg1	APPROACH					881:888	APPROACH	881:888	APPROACH	881:888	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	4	36	theme	O-linked	983:990	arg1	G					1034:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	3	37	theme	inflammation	843:854	arg1	inhibition					829:838	glucosamine-mediated inhibition	808:838	glucosamine-mediated inhibition of inflammation and vascular protection	808:878	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	3	38	dep	known	714:718	arg1	also					709:712	also	709:712	also	709:712	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	1	39	theme	smooth	376:381	arg1	cells					390:394	isolated vascular smooth muscle cells	358:394	isolated vascular smooth muscle cells	358:394	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	10	40	theme	A20	2241:2243	arg1	O-GlcNAcylation					2222:2236	O-GlcNAcylation	2222:2236	O-GlcNAcylation of A20	2222:2243	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	6	41	from	degradation	1419:1429	arg1	activity					1482:1489	DNA-binding activity	1470:1489	DNA-binding activity	1470:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	0	42	theme	Arterial	171:178	arg1	Injury					180:185	Acute Endoluminal Arterial Injury	153:185	Acute Endoluminal Arterial Injury	153:185	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	5	43	theme	key	1218:1220	arg1	protein					1233:1239	a key regulatory protein	1216:1239	a key regulatory protein for A20 activity	1216:1256	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	5	43	theme	key	1218:1220	arg1	TAX1BP1					1182:1188	TAX1BP1	1182:1188	TAX1BP1 (Tax1-binding protein 1)	1182:1213	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	7	44	theme	endogenous	1688:1697	arg1	A20					1699:1701	silencing endogenous A20	1678:1701	silencing endogenous A20 by transfection of specific A20 shRNA	1678:1739	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	10	45	theme	vascular	2452:2459	arg1	injury					2461:2466	inflammation-induced vascular injury	2431:2466	inflammation-induced vascular injury	2431:2466	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	6	46	theme	phosphorylation	1436:1450	arg1	prevention					1343:1352	prevention	1343:1352	prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity	1343:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	5	47	theme	Tax1-binding	1191:1202	arg1	TAX1BP1					1182:1188	TAX1BP1	1182:1188	TAX1BP1 (Tax1-binding protein 1)	1182:1213	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	5	47	theme	Tax1-binding	1191:1202	arg1	protein					1204:1210	Tax1-binding protein 1	1191:1212	Tax1-binding protein 1	1191:1212	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	10	48	from	regulation	2278:2287	arg1	cells					2357:2361	TNF-α-treated vascular smooth muscle cells	2320:2361	TNF-α-treated vascular smooth muscle cells in culture	2320:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	0	49	theme	Activation	104:113	arg1	Inhibition					64:73	the Inhibition	60:73	the Inhibition of NF-κB (Nuclear Factor-κB) Activation	60:113	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	5	50	theme	Thiamet	1081:1087	arg1	treatment					1091:1099	Thiamet G treatment	1081:1099	Thiamet G treatment	1081:1099	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	9	51	theme	A20	1970:1972	arg1	shRNA					1974:1978	A20 shRNA	1970:1978	A20 shRNA	1970:1978	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	0	52	theme	NF-κB	78:82	arg1	Activation					104:113	NF-κB (Nuclear Factor-κB) Activation	78:113	NF-κB (Nuclear Factor-κB) Activation	78:113	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	0	53	theme	O-Linked	0:7	arg1	Modification					31:42	O-Linked β-N-Acetylglucosamine Modification	0:42	O-Linked β-N-Acetylglucosamine Modification of A20	0:49	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	1	54	theme	O-GlcNAc	316:323	arg1	levels					326:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	10	55	from	cascades	2308:2315	arg1	cells					2357:2361	TNF-α-treated vascular smooth muscle cells	2320:2361	TNF-α-treated vascular smooth muscle cells in culture	2320:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	1	56	from	formation	411:419	arg1	cells					390:394	isolated vascular smooth muscle cells	358:394	isolated vascular smooth muscle cells	358:394	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	1	56	from	formation	411:419	arg1	model					430:434	a rat model	424:434	a rat model of carotid injury	424:452	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	1	57	theme	levels	326:331	arg1	augmentation					260:271	acute glucosamine-induced augmentation	234:271	acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	234:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	9	58	theme	injured	1987:1993	arg1	arteries					1995:2002	the injured arteries	1983:2002	the injured arteries	1983:2002	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	10	59	theme	vascular	2334:2341	arg1	cells					2357:2361	TNF-α-treated vascular smooth muscle cells	2320:2361	TNF-α-treated vascular smooth muscle cells in culture	2320:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	3	60	theme	A20	704:706	arg1	O-GlcNAcylation					776:790	increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation	694:790	increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation	694:790	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	0	61	theme	A20	47:49	arg1	Modification					31:42	O-Linked β-N-Acetylglucosamine Modification	0:42	O-Linked β-N-Acetylglucosamine Modification of A20	0:49	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	7	62	theme	cell	1636:1639	arg1	migration					1641:1649	vascular smooth muscle cell migration	1613:1649	vascular smooth muscle cell migration	1613:1649	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	5	63	theme	A20	1118:1120	arg1	expression					1130:1139	A20 protein expression	1118:1139	A20 protein expression	1118:1139	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	2	64	theme	specific	524:531	arg1	responsible					578:588	responsible	578:588	responsible	578:588	However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear.
29622561	2	64	theme	specific	524:531	arg1	target					543:548	the specific molecular target	520:548	the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection	520:632	However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear.
29622561	5	65	theme	A20	1245:1247	arg1	activity					1249:1256	A20 activity	1245:1256	A20 activity	1245:1256	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	6	66	from	increases	1457:1465	arg1	activity					1482:1489	DNA-binding activity	1470:1489	DNA-binding activity	1470:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	7	67	theme	smooth	1622:1627	arg1	migration					1641:1649	vascular smooth muscle cell migration	1613:1649	vascular smooth muscle cell migration	1613:1649	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	9	68	theme	balloon	2025:2031	arg1	expression					2052:2061	balloon injury-induced A20 expression	2025:2061	balloon injury-induced A20 expression	2025:2061	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	10	69	from	cells	2357:2361	arg1	regulation					2278:2287	the negative regulation	2265:2287	the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture	2265:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	10	69	from	cells	2357:2361	arg1	culture					2366:2372	culture	2366:2372	culture	2366:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	1	70	theme	acute	234:238	arg1	augmentation					260:271	acute glucosamine-induced augmentation	234:271	acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	234:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	9	71	theme	A20	2048:2050	arg1	expression					2052:2061	balloon injury-induced A20 expression	2025:2061	balloon injury-induced A20 expression	2025:2061	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	8	72	theme	balloon-injured	1795:1809	arg1	arteries					1823:1830	balloon-injured rat carotid arteries	1795:1830	balloon-injured rat carotid arteries	1795:1830	In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment.
29622561	7	73	theme	cytokine	1589:1596	arg1	expression					1598:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	10	74	theme	cascades	2308:2315	arg1	regulation					2278:2287	the negative regulation	2265:2287	the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture	2265:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	4	75	link	O-linked	983:990	arg1	APPROACH					881:888	APPROACH	881:888	APPROACH	881:888	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	4	75	link	O-linked	983:990	arg1	G					1034:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	6	76	theme	increases	1457:1465	arg1	prevention					1343:1352	prevention	1343:1352	prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity	1343:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	8	77	theme	carotid	1815:1821	arg1	arteries					1823:1830	balloon-injured rat carotid arteries	1795:1830	balloon-injured rat carotid arteries	1795:1830	In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment.
29622561	1	78	theme	protein	276:282	arg1	levels					326:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	10	79	dep	CONCLUSIONS	2183:2193	arg1	suggest					2209:2215	suggest	2209:2215	suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury	2209:2466	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	7	80	theme	TNF-α-induced	1559:1571	arg1	expression					1598:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	4	81	theme	smooth	927:932	arg1	cells					941:945	cultured rat vascular smooth muscle cells	905:945	cultured rat vascular smooth muscle cells	905:945	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	10	82	theme	NF-κB	2292:2296	arg1	cascades					2308:2315	NF-κB signaling cascades	2292:2315	NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture	2292:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	3	83	theme	[tumor	731:736	arg1	factor					747:752	TNFAIP3 [tumor necrosis factor	723:752	TNFAIP3 [tumor necrosis factor α-induced protein 3	723:772	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	1	84	from	inflammation	342:353	arg1	cells					390:394	isolated vascular smooth muscle cells	358:394	isolated vascular smooth muscle cells	358:394	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	1	84	from	inflammation	342:353	arg1	model					430:434	a rat model	424:434	a rat model of carotid injury	424:452	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	1	85	theme	β-N-acetylglucosamine	293:313	arg1	levels					326:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	7	86	theme	G	1554:1554	arg1	effects					1535:1541	the inhibitory effects	1520:1541	the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation	1520:1667	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	6	87	theme	A20	1279:1281	arg1	overexpression					1283:1296	Adenovirus-mediated A20 overexpression	1259:1296	Adenovirus-mediated A20 overexpression	1259:1296	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	10	88	theme	smooth	2343:2348	arg1	cells					2357:2361	TNF-α-treated vascular smooth muscle cells	2320:2361	TNF-α-treated vascular smooth muscle cells in culture	2320:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	1	89	link	O-linked	284:291	arg1	levels					326:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	276:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	10	90	theme	TNF-α-treated	2320:2332	arg1	cells					2357:2361	TNF-α-treated vascular smooth muscle cells	2320:2361	TNF-α-treated vascular smooth muscle cells in culture	2320:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	1	91	theme	isolated	358:365	arg1	cells					390:394	isolated vascular smooth muscle cells	358:394	isolated vascular smooth muscle cells	358:394	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	6	92	dep	-induced	1388:1395	arg1	factor-α					1379:1386	tumor necrosis factor-α	1364:1386	tumor necrosis factor-α	1364:1386	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	7	93	theme	inhibitory	1772:1781	arg1	effects					1783:1789	these inhibitory effects	1766:1789	these inhibitory effects	1766:1789	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	4	94	theme	rat	914:916	arg1	cells					941:945	cultured rat vascular smooth muscle cells	905:945	cultured rat vascular smooth muscle cells	905:945	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	6	95	theme	degradation	1419:1429	arg1	prevention					1343:1352	prevention	1343:1352	prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity	1343:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	4	96	theme	selective	973:981	arg1	APPROACH					881:888	APPROACH	881:888	APPROACH	881:888	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	4	96	theme	selective	973:981	arg1	G					1034:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	6	97	theme	κB	1415:1416	arg1	inhibitor					1402:1410	inhibitor	1402:1410	inhibitor of κB	1402:1416	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	8	98	theme	p65	1899:1901	arg1	activation					1903:1912	p65 activation	1899:1912	p65 activation	1899:1912	In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment.
29622561	7	99	theme	shRNA	1735:1739	arg1	transfection					1706:1717	transfection	1706:1717	transfection of specific A20 shRNA	1706:1739	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	4	100	theme	N-acetylglucosaminidase	992:1014	arg1	APPROACH					881:888	APPROACH	881:888	APPROACH	881:888	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	4	100	theme	N-acetylglucosaminidase	992:1014	arg1	G					1034:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	6	101	theme	G	1338:1338	arg1	effects					1319:1325	the effects	1315:1325	the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity	1315:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	10	102	theme	injured	2389:2395	arg1	arteries					2397:2404	acutely injured arteries	2381:2404	acutely injured arteries	2381:2404	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	0	103	theme	Endoluminal	159:169	arg1	Injury					180:185	Acute Endoluminal Arterial Injury	153:185	Acute Endoluminal Arterial Injury	153:185	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	1	104	theme	carotid	439:445	arg1	injury					447:452	carotid injury	439:452	carotid injury	439:452	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	7	105	dep	enhanced	1511:1518	arg1	whereas					1670:1676	whereas	1670:1676	whereas	1670:1676	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	7	106	theme	specific	1722:1729	arg1	shRNA					1735:1739	specific A20 shRNA	1722:1739	specific A20 shRNA	1722:1739	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	0	107	theme	Vascular	127:134	arg1	Protection					136:145	Vascular Protection	127:145	Vascular Protection	127:145	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	9	108	theme	glucosamine	2170:2180	arg1	protection					2156:2165	the vascular protection	2143:2165	the vascular protection of glucosamine	2143:2180	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	3	109	theme	glucosamine-mediated	808:827	arg1	inhibition					829:838	glucosamine-mediated inhibition	808:838	glucosamine-mediated inhibition of inflammation and vascular protection	808:878	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	6	110	theme	IκB	1397:1399	arg1	degradation					1419:1429	TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation	1357:1429	TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation	1357:1429	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	6	111	from	activity	1482:1489	arg1	prevention					1343:1352	prevention	1343:1352	prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity	1343:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	8	112	theme	vehicle	1928:1934	arg1	treatment					1936:1944	vehicle treatment	1928:1944	vehicle treatment	1928:1944	In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment.
29622561	2	113	theme	vascular	614:621	arg1	protection					623:632	glucosamine-induced vascular protection	594:632	glucosamine-induced vascular protection	594:632	However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear.
29622561	3	114	theme	protection	869:878	arg1	inhibition					829:838	glucosamine-mediated inhibition	808:838	glucosamine-mediated inhibition of inflammation and vascular protection	808:878	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	6	115	theme	DNA-binding	1470:1480	arg1	activity					1482:1489	DNA-binding activity	1470:1489	DNA-binding activity	1470:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	10	116	theme	negative	2269:2276	arg1	regulation					2278:2287	the negative regulation	2265:2287	the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture	2265:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	4	117	theme	A20	1060:1062	arg1	O-GlcNAcylation					1064:1078	A20 O-GlcNAcylation	1060:1078	A20 O-GlcNAcylation	1060:1078	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	9	118	theme	Adenoviral	1947:1956	arg1	delivery					1958:1965	Adenoviral delivery	1947:1965	Adenoviral delivery of A20 shRNA to the injured arteries	1947:2002	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	0	119	theme	Nuclear	85:91	arg1	NF-κB					78:82	NF-κB	78:82	NF-κB (Nuclear Factor-κB) Activation	78:113	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	0	119	theme	Nuclear	85:91	arg1	Factor-κB					93:101	Nuclear Factor-κB	85:101	Nuclear Factor-κB	85:101	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	1	120	theme	muscle	383:388	arg1	cells					390:394	isolated vascular smooth muscle cells	358:394	isolated vascular smooth muscle cells	358:394	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	1	121	theme	neointimal	400:409	arg1	formation					411:419	neointimal formation	400:419	neointimal formation in a rat model of carotid injury	400:452	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	7	122	theme	silencing	1678:1686	arg1	A20					1699:1701	silencing endogenous A20	1678:1701	silencing endogenous A20 by transfection of specific A20 shRNA	1678:1739	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	6	123	from	effects	1319:1325	arg1	prevention					1343:1352	prevention	1343:1352	prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity	1343:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	10	124	theme	key	2253:2255	arg1	role					2257:2260	a key role	2251:2260	a key role	2251:2260	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	5	125	theme	regulatory	1222:1231	arg1	protein					1233:1239	a key regulatory protein	1216:1239	a key regulatory protein for A20 activity	1216:1256	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	5	125	theme	regulatory	1222:1231	arg1	TAX1BP1					1182:1188	TAX1BP1	1182:1188	TAX1BP1 (Tax1-binding protein 1)	1182:1213	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	7	126	from	effects	1535:1541	arg1	migration					1641:1649	vascular smooth muscle cell migration	1613:1649	vascular smooth muscle cell migration	1613:1649	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	7	126	from	effects	1535:1541	arg1	expression					1598:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	TNF-α-induced proinflammatory cytokine expression	1559:1607	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	4	127	theme	thiamet	1026:1032	arg1	APPROACH					881:888	APPROACH	881:888	APPROACH	881:888	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	4	127	theme	thiamet	1026:1032	arg1	G					1034:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	the selective O-linked N-acetylglucosaminidase inhibitor thiamet G	969:1034	APPROACH AND RESULTS In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation.
29622561	10	128	theme	inflammation-induced	2431:2450	arg1	injury					2461:2466	inflammation-induced vascular injury	2431:2466	inflammation-induced vascular injury	2431:2466	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	6	129	theme	p65	1432:1434	arg1	phosphorylation					1436:1450	p65 phosphorylation	1432:1450	p65 phosphorylation	1432:1450	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	0	130	theme	β-N-Acetylglucosamine	9:29	arg1	Modification					31:42	O-Linked β-N-Acetylglucosamine Modification	0:42	O-Linked β-N-Acetylglucosamine Modification of A20	0:49	O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.
29622561	6	131	from	phosphorylation	1436:1450	arg1	activity					1482:1489	DNA-binding activity	1470:1489	DNA-binding activity	1470:1489	Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity.
29622561	9	132	theme	shRNA	1974:1978	arg1	delivery					1958:1965	Adenoviral delivery	1947:1965	Adenoviral delivery of A20 shRNA to the injured arteries	1947:2002	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	3	133	theme	increased	694:702	arg1	O-GlcNAcylation					776:790	increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation	694:790	increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation	694:790	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	10	134	theme	muscle	2350:2355	arg1	cells					2357:2361	TNF-α-treated vascular smooth muscle cells	2320:2361	TNF-α-treated vascular smooth muscle cells in culture	2320:2372	CONCLUSIONS These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.
29622561	3	135	dep	factor	747:752	arg1	protein					764:770	α-induced protein 3	754:772	TNFAIP3 [tumor necrosis factor α-induced protein 3	723:772	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	5	136	theme	protein	1122:1128	arg1	expression					1130:1139	A20 protein expression	1118:1139	A20 protein expression	1118:1139	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	1	137	dep	OBJECTIVE	188:196	arg1	demonstrated					216:227	demonstrated	216:227	have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling	211:508	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	1	138	theme	vascular	367:374	arg1	cells					390:394	isolated vascular smooth muscle cells	358:394	isolated vascular smooth muscle cells	358:394	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	7	139	theme	muscle	1629:1634	arg1	migration					1641:1649	vascular smooth muscle cell migration	1613:1649	vascular smooth muscle cell migration	1613:1649	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	5	140	theme	G	1089:1089	arg1	treatment					1091:1099	Thiamet G treatment	1081:1099	Thiamet G treatment	1081:1099	Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity.
29622561	9	141	theme	injury-induced	2033:2046	arg1	expression					2052:2061	balloon injury-induced A20 expression	2025:2061	balloon injury-induced A20 expression	2025:2061	Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine.
29622561	8	142	theme	rat	1811:1813	arg1	arteries					1823:1830	balloon-injured rat carotid arteries	1795:1830	balloon-injured rat carotid arteries	1795:1830	In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment.
29622561	1	143	theme	glucosamine-induced	240:258	arg1	augmentation					260:271	acute glucosamine-induced augmentation	234:271	acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels	234:331	OBJECTIVE Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling.
29622561	7	144	theme	vascular	1613:1620	arg1	migration					1641:1649	vascular smooth muscle cell migration	1613:1649	vascular smooth muscle cell migration	1613:1649	A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects.
29622561	3	145	theme	necrosis	738:745	arg1	factor					747:752	TNFAIP3 [tumor necrosis factor	723:752	TNFAIP3 [tumor necrosis factor α-induced protein 3	723:772	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
29622561	3	146	dep	A20	704:706	arg1	known					714:718	known	714:718	known as TNFAIP3 [tumor necrosis factor α-induced protein 3	714:772	In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection.
31117711	1	0	theme	cascade	258:264	arg1	process					266:272	a cascade process	256:272	a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization	256:396	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	1	1	theme	N-linked	160:167	arg1	structure					176:184	An N-linked indole structure	157:184	An N-linked indole structure	157:184	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	0	2	theme	Total	119:123	arg1	Synthesis					125:133	Total Synthesis	119:133	Total Synthesis of (+)-Pestalazine B	119:154	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	0	3	from	Construction	0:11	arg1	Pyrroloindolines					36:51	Pyrroloindolines	36:51	Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade	36:101	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	4	4	theme	total	753:757	arg1	synthesis					759:767	the total synthesis	749:767	the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B	749:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	2	5	theme	π-Lewis	531:537	arg1	acid					539:542	a π-Lewis acid	529:542	a π-Lewis acid	529:542	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	1	6	dep	subsequent	363:372	arg1	5-					374:375	5-	374:375	5-	374:375	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	1	7	with	2-ethynylanilines	340:356	arg1	cyclization					386:396	subsequent 5- endo-dig cyclization	363:396	subsequent 5- endo-dig cyclization	363:396	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	1	8	theme	silver-mediated	284:298	arg1	amination					300:308	silver-mediated amination	284:308	silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization	284:396	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	4	9	theme	indole	782:787	arg1	alkaloid					789:796	a dimeric indole alkaloid	772:796	a dimeric indole alkaloid	772:796	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	9	theme	indole	782:787	arg1	B					815:815	(+)-pestalazine B	799:815	B	815:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	1	10	theme	indole	169:174	arg1	structure					176:184	An N-linked indole structure	157:184	An N-linked indole structure	157:184	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	1	11	with	bromopyrroloindolines	313:333	arg1	2-ethynylanilines					340:356	2-ethynylanilines	340:356	2-ethynylanilines with subsequent 5- endo-dig cyclization	340:396	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	4	12	theme	dimeric	774:780	arg1	alkaloid					789:796	a dimeric indole alkaloid	772:796	a dimeric indole alkaloid	772:796	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	12	theme	dimeric	774:780	arg1	B					815:815	(+)-pestalazine B	799:815	B	815:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	2	13	theme	bromo	474:478	arg1	group					480:484	the bromo group	470:484	the bromo group as a σ-Lewis acid	470:502	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	0	14	theme	Structure	23:31	arg1	Construction					0:11	Construction	0:11	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.	0:155	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	3	15	theme	initial	564:570	arg1	step					572:575	the initial step	560:575	the initial step	560:575	Switching from the initial step to the second step was conducted by controlling the temperature.
31117711	0	16	theme	Indole	16:21	arg1	Structure					23:31	Indole Structure	16:31	Indole Structure	16:31	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	1	17	theme	bromopyrroloindolines	313:333	arg1	amination					300:308	silver-mediated amination	284:308	silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization	284:396	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	1	18	link	N-linked	160:167	arg1	structure					176:184	An N-linked indole structure	157:184	An N-linked indole structure	157:184	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	4	19	theme	pyrroloindolines	696:711	arg1	synthesis					759:767	the total synthesis	749:767	the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B	749:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	19	theme	pyrroloindolines	696:711	arg1	synthesis					675:683	the synthesis	671:683	the synthesis of various pyrroloindolines, α-carboline, and furoindolines	671:743	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	0	20	theme	-Pestalazine	141:152	arg1	B					154:154	(+)-Pestalazine B	138:154	(+)-Pestalazine B	138:154	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	4	21	theme	-pestalazine	802:813	arg1	alkaloid					789:796	a dimeric indole alkaloid	772:796	a dimeric indole alkaloid	772:796	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	21	theme	-pestalazine	802:813	arg1	B					815:815	(+)-pestalazine B	799:815	B	815:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	2	22	theme	σ-Lewis	491:497	arg1	acid					499:502	a σ-Lewis acid	489:502	a σ-Lewis acid	489:502	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	2	23	theme	tandem	438:443	arg1	reagent					445:451	a tandem reagent	436:451	a tandem reagent	436:451	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	2	23	theme	tandem	438:443	arg1	AgNTf2					417:422	AgNTf2	417:422	AgNTf2	417:422	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	0	24	theme	AgNTf2-Mediated	57:71	arg1	Cascade					95:101	AgNTf2-Mediated Amination/Cyclization Cascade	57:101	AgNTf2-Mediated Amination/Cyclization Cascade	57:101	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	2	25	theme	alkyne	512:517	arg1	moiety					519:524	the alkyne moiety	508:524	the alkyne moiety as a π-Lewis acid	508:542	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	3	26	theme	second	584:589	arg1	step					591:594	the second step	580:594	the second step	580:594	Switching from the initial step to the second step was conducted by controlling the temperature.
31117711	1	27	theme	subsequent	363:372	arg1	cyclization					386:396	subsequent 5- endo-dig cyclization	363:396	subsequent 5- endo-dig cyclization	363:396	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	0	28	theme	B	154:154	arg1	Synthesis					125:133	Total Synthesis	119:133	Total Synthesis of (+)-Pestalazine B	119:154	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	4	29	theme	α-carboline	714:724	arg1	synthesis					759:767	the total synthesis	749:767	the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B	749:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	29	theme	α-carboline	714:724	arg1	synthesis					675:683	the synthesis	671:683	the synthesis of various pyrroloindolines, α-carboline, and furoindolines	671:743	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	30	theme	furoindolines	731:743	arg1	synthesis					759:767	the total synthesis	749:767	the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B	749:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	30	theme	furoindolines	731:743	arg1	synthesis					675:683	the synthesis	671:683	the synthesis of various pyrroloindolines, α-carboline, and furoindolines	671:743	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	3	31	from	step	572:575	arg1	Switching					545:553	Switching	545:553	Switching from the initial step to the second step	545:594	Switching from the initial step to the second step was conducted by controlling the temperature.
31117711	1	32	theme	pyrroloindoline	224:238	arg1	derivatives					240:250	pyrroloindoline derivatives	224:250	pyrroloindoline derivatives	224:250	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	4	33	theme	alkaloid	789:796	arg1	synthesis					759:767	the total synthesis	749:767	the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B	749:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	33	theme	alkaloid	789:796	arg1	synthesis					675:683	the synthesis	671:683	the synthesis of various pyrroloindolines, α-carboline, and furoindolines	671:743	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	0	34	dep	B	154:154	arg1	+					139:139	+	139:139	+	139:139	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	1	35	theme	derivatives	240:250	arg1	3a-position					209:219	the 3a-position	205:219	the 3a-position of pyrroloindoline derivatives	205:250	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	4	36	theme	+	800:800	arg1	alkaloid					789:796	a dimeric indole alkaloid	772:796	a dimeric indole alkaloid	772:796	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	4	36	theme	+	800:800	arg1	B					815:815	(+)-pestalazine B	799:815	B	815:815	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	2	37	used	used	428:431	arg2	AgNTf2					417:422	AgNTf2	417:422	AgNTf2	417:422	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	2	37	used	used	428:431	arg2	reagent					445:451	a tandem reagent	436:451	a tandem reagent	436:451	In this reaction, AgNTf2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid.
31117711	4	38	theme	various	688:694	arg1	pyrroloindolines					696:711	various pyrroloindolines	688:711	various pyrroloindolines	688:711	This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.
31117711	0	39	theme	Amination/Cyclization	73:93	arg1	Cascade					95:101	AgNTf2-Mediated Amination/Cyclization Cascade	57:101	AgNTf2-Mediated Amination/Cyclization Cascade	57:101	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31117711	1	40	theme	endo-dig	377:384	arg1	cyclization					386:396	subsequent 5- endo-dig cyclization	363:396	subsequent 5- endo-dig cyclization	363:396	An N-linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization.
31117711	0	41	dep	Construction	0:11	arg1	Application					104:114	Application	104:114	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.	0:155	Construction of Indole Structure on Pyrroloindolines via AgNTf2-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B.
31682414	1	0	theme	Caenorhabditis	180:193	arg1	elegans					195:201	Caenorhabditis elegans	180:201	Caenorhabditis elegans	180:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	0	1	from	Profiling	15:23	arg1	elegans					62:68	Caenorhabditis elegans	47:68	Caenorhabditis elegans	47:68	Chemoproteomic Profiling of O-GlcNAcylation in Caenorhabditis elegans.
31682414	6	2	from	set	811:813	arg1	study					823:827	this study	818:827	this study	818:827	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	3	3	from	sites	485:489	arg1	elegans					497:503	C. elegans	494:503	C. elegans	494:503	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	1	4	from	elegans	195:201	arg1	functions					111:119	essential functions	101:119	essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans	101:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	1	5	theme	Genetic	71:77	arg1	studies					79:85	Genetic studies	71:85	Genetic studies	71:85	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	4	6	theme	altering	548:555	arg1	O-GlcNAcylation					557:571	altering O-GlcNAcylation	548:571	altering O-GlcNAcylation	548:571	Furthermore, quantitative proteomics upon altering O-GlcNAcylation show that the abundance of a large number of proteins are affected by O-GlcNAc.
31682414	1	7	from	modification	164:175	arg1	elegans					195:201	Caenorhabditis elegans	180:201	Caenorhabditis elegans	180:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	6	8	from	elegans	879:885	arg1	landscape					863:871	landscape	863:871	landscape	863:871	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	6	9	theme	O-GlcNAcylation	962:976	arg1	function					950:957	the biological function	935:957	the biological function of O-GlcNAcylation	935:976	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	3	10	theme	modification	472:483	arg1	sites					485:489	64 modification sites	469:489	64 modification sites	469:489	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	3	11	theme	proteins	456:463	arg1	identification					403:416	the identification	399:416	the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans	399:503	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	3	12	theme	O-GlcNAcylated	441:454	arg1	proteins					456:463	108 high-confidence O-GlcNAcylated proteins	421:463	108 high-confidence O-GlcNAcylated proteins	421:463	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	3	13	from	proteins	456:463	arg1	elegans					497:503	C. elegans	494:503	C. elegans	494:503	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	6	14	theme	landscape	863:871	arg1	modification					850:861	the O-GlcNAc modification	837:861	the O-GlcNAc modification landscape in C. elegans	837:885	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	1	15	theme	essential	101:109	arg1	functions					111:119	essential functions	101:119	essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans	101:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	0	16	theme	Chemoproteomic	0:13	arg1	Profiling					15:23	Chemoproteomic Profiling	0:23	Chemoproteomic Profiling of O-GlcNAcylation in Caenorhabditis elegans	0:68	Chemoproteomic Profiling of O-GlcNAcylation in Caenorhabditis elegans.
31682414	0	17	theme	O-GlcNAcylation	28:42	arg1	Profiling					15:23	Chemoproteomic Profiling	0:23	Chemoproteomic Profiling of O-GlcNAcylation in Caenorhabditis elegans	0:68	Chemoproteomic Profiling of O-GlcNAcylation in Caenorhabditis elegans.
31682414	4	18	theme	proteins	618:625	arg1	number					608:613	a large number	600:613	a large number of proteins	600:625	Furthermore, quantitative proteomics upon altering O-GlcNAcylation show that the abundance of a large number of proteins are affected by O-GlcNAc.
31682414	6	19	theme	O-GlcNAc	841:848	arg1	modification					850:861	the O-GlcNAc modification	837:861	the O-GlcNAc modification landscape in C. elegans	837:885	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	2	20	from	sites	296:300	arg1	elegans					308:314	C. elegans	305:314	C. elegans	305:314	However, large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans remain relatively unexplored.
31682414	3	21	theme	high-confidence	425:439	arg1	proteins					456:463	108 high-confidence O-GlcNAcylated proteins	421:463	108 high-confidence O-GlcNAcylated proteins	421:463	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	5	22	theme	genetic	785:791	arg1	studies					793:799	genetic studies	785:799	genetic studies	785:799	These proteins are involved in regulating reproduction and lifespan, which may correlate with the previously observed phenotypes in genetic studies.
31682414	2	23	theme	large-scale	213:223	arg1	identification					225:238	large-scale identification	213:238	large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans	213:314	However, large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans remain relatively unexplored.
31682414	1	24	theme	O-linked	124:131	arg1	O-GlcNAc					154:161	O-GlcNAc	154:161	O-GlcNAc	154:161	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	1	24	theme	O-linked	124:131	arg1	N-acetylglucosamine					133:151	O-linked N-acetylglucosamine	124:151	O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans	124:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	0	25	theme	Caenorhabditis	47:60	arg1	elegans					62:68	Caenorhabditis elegans	47:68	Caenorhabditis elegans	47:68	Chemoproteomic Profiling of O-GlcNAcylation in Caenorhabditis elegans.
31682414	6	26	theme	biological	939:948	arg1	function					950:957	the biological function	935:957	the biological function of O-GlcNAcylation	935:976	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	2	27	theme	modification	283:294	arg1	sites					296:300	the modification sites	279:300	the modification sites in C. elegans	279:314	However, large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans remain relatively unexplored.
31682414	3	28	theme	sites	485:489	arg1	identification					403:416	the identification	399:416	the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans	399:503	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	4	29	theme	large	602:606	arg1	number					608:613	a large number	600:613	a large number of proteins	600:625	Furthermore, quantitative proteomics upon altering O-GlcNAcylation show that the abundance of a large number of proteins are affected by O-GlcNAc.
31682414	3	30	from	identification	403:416	arg1	elegans					497:503	C. elegans	494:503	C. elegans	494:503	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	6	31	from	landscape	863:871	arg1	elegans					879:885	C. elegans	876:885	C. elegans	876:885	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	4	32	theme	quantitative	519:530	arg1	proteomics					532:541	quantitative proteomics	519:541	quantitative proteomics upon altering O-GlcNAcylation	519:571	Furthermore, quantitative proteomics upon altering O-GlcNAcylation show that the abundance of a large number of proteins are affected by O-GlcNAc.
31682414	1	33	theme	N-acetylglucosamine	133:151	arg1	modification					164:175	O-linked N-acetylglucosamine (O-GlcNAc) modification	124:175	O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans	124:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	3	34	theme	chemoproteomic	357:370	arg1	strategy					372:379	a chemoproteomic strategy	355:379	a chemoproteomic strategy	355:379	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31682414	2	35	theme	proteins	258:265	arg1	identification					225:238	large-scale identification	213:238	large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans	213:314	However, large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans remain relatively unexplored.
31682414	4	36	theme	number	608:613	arg1	abundance					587:595	the abundance	583:595	the abundance of a large number of proteins	583:625	Furthermore, quantitative proteomics upon altering O-GlcNAcylation show that the abundance of a large number of proteins are affected by O-GlcNAc.
31682414	5	37	theme	observed	762:769	arg1	phenotypes					771:780	the previously observed phenotypes	747:780	the previously observed phenotypes in genetic studies	747:799	These proteins are involved in regulating reproduction and lifespan, which may correlate with the previously observed phenotypes in genetic studies.
31682414	2	38	theme	O-GlcNAcylated	243:256	arg1	proteins					258:265	O-GlcNAcylated proteins	243:265	O-GlcNAcylated proteins and mapping the modification sites in C. elegans	243:314	However, large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans remain relatively unexplored.
31682414	6	39	theme	data	806:809	arg1	set					811:813	The data set	802:813	The data set in this study	802:827	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	6	40	theme	valuable	902:909	arg1	resource					911:918	a valuable resource	900:918	a valuable resource for dissecting the biological function of O-GlcNAcylation	900:976	The data set in this study reveals the O-GlcNAc modification landscape in C. elegans and provides a valuable resource for dissecting the biological function of O-GlcNAcylation.
31682414	5	41	from	phenotypes	771:780	arg1	studies					793:799	genetic studies	785:799	genetic studies	785:799	These proteins are involved in regulating reproduction and lifespan, which may correlate with the previously observed phenotypes in genetic studies.
31682414	1	42	theme	modification	164:175	arg1	functions					111:119	essential functions	101:119	essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans	101:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	1	43	from	functions	111:119	arg1	elegans					195:201	Caenorhabditis elegans	180:201	Caenorhabditis elegans	180:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	2	44	dep	proteins	258:265	arg1	mapping					271:277	mapping	271:277	mapping the modification sites in C. elegans	271:314	However, large-scale identification of O-GlcNAcylated proteins and mapping the modification sites in C. elegans remain relatively unexplored.
31682414	1	45	link	O-linked	124:131	arg1	O-GlcNAc					154:161	O-GlcNAc	154:161	O-GlcNAc	154:161	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	1	45	link	O-linked	124:131	arg1	N-acetylglucosamine					133:151	O-linked N-acetylglucosamine	124:151	O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans	124:201	Genetic studies have revealed essential functions of O-linked N-acetylglucosamine (O-GlcNAc) modification in Caenorhabditis elegans.
31682414	3	46	from	elegans	497:503	arg1	identification					403:416	the identification	399:416	the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans	399:503	By using a chemoproteomic strategy, we herein report the identification of 108 high-confidence O-GlcNAcylated proteins and 64 modification sites in C. elegans.
31308178	0	0	theme	receptor	106:113	arg1	signaling					58:66	signaling	58:66	signaling	58:66	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	0	0	theme	receptor	106:113	arg1	activation					43:52	activation	43:52	activation	43:52	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	1	1	gly	glycosylation	202:214	arg1	proteins					232:239	cell-surface proteins	219:239	cell-surface proteins	219:239	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	1	1	gly	glycosylation	202:214	arg1	cells					256:260	endothelial cells	244:260	endothelial cells	244:260	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	1	2	from	glycosylation	202:214	arg1	cells					256:260	endothelial cells	244:260	endothelial cells	244:260	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	4	3	theme	N-linked	798:805	arg1	glycans					807:813	N-linked glycans	798:813	N-linked glycans at the Asn-247 site in VEGFR2	798:843	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	0	4	theme	factor	99:104	arg1	receptor					106:113	vascular endothelial growth factor receptor 2	71:115	vascular endothelial growth factor receptor 2 (VEGFR2)	71:124	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	0	4	theme	factor	99:104	arg1	VEGFR2					118:123	VEGFR2	118:123	VEGFR2	118:123	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	2	5	with	receptor	468:475	arg1	N-glycans					512:520	sialic acid-capped N-glycans	493:520	sialic acid-capped N-glycans	493:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	4	6	from	activation	882:891	arg1	cells					922:926	endothelial cells	910:926	endothelial cells	910:926	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	2	7	theme	glycoproteins	411:423	arg1	modification					383:394	the modification	379:394	the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	379:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	5	8	theme	lower	1094:1098	arg1	levels					1100:1105	lower levels	1094:1105	lower levels of sialylated N-glycans	1094:1129	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	3	9	theme	physiological	622:634	arg1	contexts					653:660	physiological and pathological contexts	622:660	physiological and pathological contexts	622:660	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	3	9	theme	physiological	622:634	arg1	cancer					673:678	cancer	673:678	cancer	673:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	7	10	theme	endothelial	1544:1554	arg1	cells					1556:1560	endothelial cells	1544:1560	endothelial cells	1544:1560	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	6	11	theme	VEGFR2	1295:1300	arg1	activation					1302:1311	ligand-mediated VEGFR2 activation	1279:1311	ligand-mediated VEGFR2 activation	1279:1311	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	6	12	theme	ligand-mediated	1279:1293	arg1	activation					1302:1311	ligand-mediated VEGFR2 activation	1279:1311	ligand-mediated VEGFR2 activation	1279:1311	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	3	13	theme	pathological	640:651	arg1	contexts					653:660	physiological and pathological contexts	622:660	physiological and pathological contexts	622:660	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	3	13	theme	pathological	640:651	arg1	cancer					673:678	cancer	673:678	cancer	673:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	4	14	theme	VEGF	852:855	arg1	activation					882:891	VEGF ligand-mediated receptor activation	852:891	VEGF ligand-mediated receptor activation	852:891	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	5	15	theme	cell	954:957	arg1	VEGFR2					978:983	cell surface-associated VEGFR2	954:983	cell surface-associated VEGFR2	954:983	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	7	16	from	capping	1435:1441	arg1	Asn-247					1459:1465	Asn-247	1459:1465	Asn-247	1459:1465	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	3	17	theme	receptor	557:564	arg1	VEGFR2					523:528	VEGFR2	523:528	VEGFR2	523:528	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	3	17	theme	receptor	557:564	arg1	kinase					575:580	a highly N-glycosylated receptor tyrosine kinase	533:580	a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer	533:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	5	18	contain	contain	1086:1092	arg1	sites					1060:1064	the nearby sites	1049:1064	the nearby sites Asn-145 and Asn-160	1049:1084	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	18	contain	contain	1086:1092	arg2	levels					1100:1105	lower levels	1094:1105	lower levels of sialylated N-glycans	1094:1129	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	18	contain	contain	1086:1092	arg2	levels					1142:1147	higher levels	1135:1147	higher levels of high-mannose N-glycans	1135:1173	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	18	contain	contain	1086:1092	arg1	Asn-160					1078:1084	Asn-160	1078:1084	Asn-160	1078:1084	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	18	contain	contain	1086:1092	arg1	Asn-145					1066:1072	Asn-145	1066:1072	Asn-145	1066:1072	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	4	19	theme	MS-based	759:766	arg1	analyses					768:775	immunoprecipitation and MS-based analyses	735:775	immunoprecipitation and MS-based analyses	735:775	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	5	20	gly	sialylated	1110:1119	arg1	N-glycans					1121:1129	sialylated N-glycans	1110:1129	sialylated N-glycans	1110:1129	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	21	dep	sites	1060:1064	arg1	sites					1060:1064	the nearby sites	1049:1064	the nearby sites Asn-145 and Asn-160	1049:1084	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	21	dep	sites	1060:1064	arg1	Asn-160					1078:1084	Asn-160	1078:1084	Asn-160	1078:1084	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	21	dep	sites	1060:1064	arg1	Asn-145					1066:1072	Asn-145	1066:1072	Asn-145	1066:1072	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	2	22	theme	endoplasmic	312:322	arg1	reticulum					324:332	the endoplasmic reticulum	308:332	the endoplasmic reticulum	308:332	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	23	theme	factor	461:466	arg1	receptor					468:475	vascular endothelial growth factor receptor 2	433:477	vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	433:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	23	theme	factor	461:466	arg1	VEGFR2					480:485	VEGFR2	480:485	VEGFR2	480:485	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	3	24	theme	pro-angiogenic	594:607	arg1	signaling					609:617	pro-angiogenic signaling	594:617	pro-angiogenic signaling in physiological and pathological contexts, including cancer	594:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	4	25	link	N-linked	798:805	arg1	glycans					807:813	N-linked glycans	798:813	N-linked glycans at the Asn-247 site in VEGFR2	798:843	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	2	26	theme	growth	454:459	arg1	receptor					468:475	vascular endothelial growth factor receptor 2	433:477	vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	433:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	26	theme	growth	454:459	arg1	VEGFR2					480:485	VEGFR2	480:485	VEGFR2	480:485	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	27	theme	acid-capped	500:510	arg1	N-glycans					512:520	sialic acid-capped N-glycans	493:520	sialic acid-capped N-glycans	493:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	5	28	theme	nearby	1053:1058	arg1	sites					1060:1064	the nearby sites	1049:1064	the nearby sites Asn-145 and Asn-160	1049:1084	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	28	theme	nearby	1053:1058	arg1	Asn-160					1078:1084	Asn-160	1078:1084	Asn-160	1078:1084	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	28	theme	nearby	1053:1058	arg1	Asn-145					1066:1072	Asn-145	1066:1072	Asn-145	1066:1072	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	2	29	from	machinery	295:303	arg1	Golgi					338:342	Golgi	338:342	Golgi	338:342	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	29	from	machinery	295:303	arg1	reticulum					324:332	the endoplasmic reticulum	308:332	the endoplasmic reticulum	308:332	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	30	theme	endothelial	442:452	arg1	receptor					468:475	vascular endothelial growth factor receptor 2	433:477	vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	433:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	30	theme	endothelial	442:452	arg1	VEGFR2					480:485	VEGFR2	480:485	VEGFR2	480:485	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	31	theme	sialic	493:498	arg1	N-glycans					512:520	sialic acid-capped N-glycans	493:520	sialic acid-capped N-glycans	493:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	5	32	theme	sialylated	1110:1119	arg1	N-glycans					1121:1129	sialylated N-glycans	1110:1129	sialylated N-glycans	1110:1129	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	4	33	from	site	830:833	arg1	VEGFR2					838:843	VEGFR2	838:843	VEGFR2	838:843	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	4	33	from	site	830:833	arg1	glycans					807:813	N-linked glycans	798:813	N-linked glycans at the Asn-247 site in VEGFR2	798:843	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	2	34	theme	proinflammatory	345:359	arg1	cytokines					361:369	proinflammatory cytokines	345:369	proinflammatory cytokines	345:369	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	1	35	theme	proteins	232:239	arg1	glycosylation					202:214	glycosylation	202:214	glycosylation of cell-surface proteins on endothelial cells	202:260	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	0	36	theme	ligand-dependent	26:41	arg1	activation					43:52	activation	43:52	activation	43:52	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	6	37	theme	uncapped	1326:1333	arg1	asialo-glycans					1335:1348	the uncapped asialo-glycans	1322:1348	the uncapped asialo-glycans	1322:1348	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	4	38	theme	kinase	717:722	arg1	assays					724:729	glycoside hydrolase and kinase assays	693:729	assays	724:729	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	7	39	theme	N-glycans	1446:1454	arg1	N-glycosylation					1401:1415	N-glycosylation	1401:1415	N-glycosylation	1401:1415	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	7	39	theme	N-glycans	1446:1454	arg1	capping					1435:1441	specifically the capping	1418:1441	specifically the capping of N-glycans at Asn-247 by sialic acid	1418:1480	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	2	40	gly	glycoproteins	411:423	arg1	receptor					468:475	vascular endothelial growth factor receptor 2	433:477	vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	433:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	40	gly	glycoproteins	411:423	arg1	glycoproteins					411:423	endothelial glycoproteins	399:423	endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	399:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	4	41	theme	immunoprecipitation	735:753	arg1	analyses					768:775	immunoprecipitation and MS-based analyses	735:775	immunoprecipitation and MS-based analyses	735:775	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	7	42	theme	VEGFR2	1534:1539	arg1	activation					1506:1515	ligand-dependent activation	1489:1515	ligand-dependent activation	1489:1515	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	7	42	theme	VEGFR2	1534:1539	arg1	signaling					1521:1529	signaling	1521:1529	signaling	1521:1529	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	1	43	theme	cell-surface	219:230	arg1	proteins					232:239	cell-surface proteins	219:239	cell-surface proteins	219:239	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	1	44	theme	endothelial	244:254	arg1	cells					256:260	endothelial cells	244:260	endothelial cells	244:260	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	7	45	from	Asn-247	1459:1465	arg1	N-glycosylation					1401:1415	N-glycosylation	1401:1415	N-glycosylation	1401:1415	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	7	45	from	Asn-247	1459:1465	arg1	N-glycans					1446:1454	N-glycans	1446:1454	N-glycans at Asn-247	1446:1465	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	7	45	from	Asn-247	1459:1465	arg1	capping					1435:1441	specifically the capping	1418:1441	specifically the capping of N-glycans at Asn-247 by sialic acid	1418:1480	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	5	46	theme	sialylated	994:1003	arg1	N-glycans					1005:1013	sialylated N-glycans	994:1013	sialylated N-glycans	994:1013	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	47	theme	higher	1135:1140	arg1	levels					1142:1147	higher levels	1135:1147	higher levels of high-mannose N-glycans	1135:1173	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	48	theme	surface-associated	959:976	arg1	VEGFR2					978:983	cell surface-associated VEGFR2	954:983	cell surface-associated VEGFR2	954:983	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	0	49	theme	vascular	71:78	arg1	receptor					106:113	vascular endothelial growth factor receptor 2	71:115	vascular endothelial growth factor receptor 2 (VEGFR2)	71:124	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	0	49	theme	vascular	71:78	arg1	VEGFR2					118:123	VEGFR2	118:123	VEGFR2	118:123	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	6	50	theme	Asn-247-linked	1225:1238	arg1	glycans					1240:1246	VEGFR2 Asn-247-linked glycans	1218:1246	VEGFR2 Asn-247-linked glycans capped with sialic acid	1218:1270	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	2	51	theme	endothelial	399:409	arg1	receptor					468:475	vascular endothelial growth factor receptor 2	433:477	vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	433:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	51	theme	endothelial	399:409	arg1	glycoproteins					411:423	endothelial glycoproteins	399:423	endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	399:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	5	52	gly	sialylated	994:1003	arg1	N-glycans					1005:1013	sialylated N-glycans	994:1013	sialylated N-glycans	994:1013	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	7	53	theme	sialic	1470:1475	arg1	acid					1477:1480	sialic acid	1470:1480	sialic acid	1470:1480	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	5	54	theme	high-mannose	1152:1163	arg1	N-glycans					1165:1173	high-mannose N-glycans	1152:1173	high-mannose N-glycans	1152:1173	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	3	55	theme	tyrosine	566:573	arg1	VEGFR2					523:528	VEGFR2	523:528	VEGFR2	523:528	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	3	55	theme	tyrosine	566:573	arg1	kinase					575:580	a highly N-glycosylated receptor tyrosine kinase	533:580	a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer	533:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	5	56	theme	N-glycans	1121:1129	arg1	levels					1100:1105	lower levels	1094:1105	lower levels of sialylated N-glycans	1094:1129	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	56	theme	N-glycans	1121:1129	arg1	levels					1142:1147	higher levels	1135:1147	higher levels of high-mannose N-glycans	1135:1173	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	57	theme	N-glycans	1165:1173	arg1	levels					1100:1105	lower levels	1094:1105	lower levels of sialylated N-glycans	1094:1129	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	5	57	theme	N-glycans	1165:1173	arg1	levels					1142:1147	higher levels	1135:1147	higher levels of high-mannose N-glycans	1135:1173	We provide evidence that cell surface-associated VEGFR2 displays sialylated N-glycans at Asn-247 and, in contrast, that the nearby sites Asn-145 and Asn-160 contain lower levels of sialylated N-glycans and higher levels of high-mannose N-glycans, respectively.
31308178	7	58	theme	ligand-dependent	1489:1504	arg1	activation					1506:1515	ligand-dependent activation	1489:1515	ligand-dependent activation	1489:1515	We propose that N-glycosylation, specifically the capping of N-glycans at Asn-247 by sialic acid, tunes ligand-dependent activation and signaling of VEGFR2 in endothelial cells.
31308178	6	59	theme	receptor	1375:1382	arg1	activation					1356:1365	activation	1356:1365	activation of this receptor	1356:1382	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	1	60	theme	tumor	131:135	arg1	microenvironment					137:152	The tumor microenvironment	127:152	The tumor microenvironment	127:152	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	3	61	gly	N-glycosylated	542:555	arg1	VEGFR2					523:528	VEGFR2	523:528	VEGFR2	523:528	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	3	61	gly	N-glycosylated	542:555	arg1	kinase					575:580	a highly N-glycosylated receptor tyrosine kinase	533:580	a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer	533:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	4	62	theme	glycoside	693:701	arg1	hydrolase					703:711	glycoside hydrolase and kinase assays	693:729	hydrolase	703:711	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	4	63	theme	receptor	873:880	arg1	activation					882:891	VEGF ligand-mediated receptor activation	852:891	VEGF ligand-mediated receptor activation	852:891	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	6	64	link	Asn-247-linked	1225:1238	arg1	glycans					1240:1246	VEGFR2 Asn-247-linked glycans	1218:1246	VEGFR2 Asn-247-linked glycans capped with sialic acid	1218:1270	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	4	65	theme	ligand-mediated	857:871	arg1	activation					882:891	VEGF ligand-mediated receptor activation	852:891	VEGF ligand-mediated receptor activation	852:891	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	3	66	theme	N-glycosylated	542:555	arg1	VEGFR2					523:528	VEGFR2	523:528	VEGFR2	523:528	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	3	66	theme	N-glycosylated	542:555	arg1	kinase					575:580	a highly N-glycosylated receptor tyrosine kinase	533:580	a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer	533:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	6	67	theme	sialic	1260:1265	arg1	acid					1267:1270	sialic acid	1260:1270	sialic acid	1260:1270	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	4	68	theme	Asn-247	822:828	arg1	site					830:833	the Asn-247 site	818:833	the Asn-247 site in VEGFR2	818:843	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	0	69	theme	growth	92:97	arg1	receptor					106:113	vascular endothelial growth factor receptor 2	71:115	vascular endothelial growth factor receptor 2 (VEGFR2)	71:124	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	0	69	theme	growth	92:97	arg1	VEGFR2					118:123	VEGFR2	118:123	VEGFR2	118:123	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	6	70	theme	VEGFR2	1218:1223	arg1	glycans					1240:1246	VEGFR2 Asn-247-linked glycans	1218:1246	VEGFR2 Asn-247-linked glycans capped with sialic acid	1218:1270	Furthermore, we report that VEGFR2 Asn-247-linked glycans capped with sialic acid oppose ligand-mediated VEGFR2 activation, whereas the uncapped asialo-glycans favor activation of this receptor.
31308178	4	71	theme	endothelial	910:920	arg1	cells					922:926	endothelial cells	910:926	endothelial cells	910:926	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	2	72	theme	vascular	433:440	arg1	receptor					468:475	vascular endothelial growth factor receptor 2	433:477	vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans	433:520	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	2	72	theme	vascular	433:440	arg1	VEGFR2					480:485	VEGFR2	480:485	VEGFR2	480:485	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	0	73	theme	endothelial	80:90	arg1	receptor					106:113	vascular endothelial growth factor receptor 2	71:115	vascular endothelial growth factor receptor 2 (VEGFR2)	71:124	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	0	73	theme	endothelial	80:90	arg1	VEGFR2					118:123	VEGFR2	118:123	VEGFR2	118:123	N-Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2).
31308178	2	74	theme	N-glycosylation	279:293	arg1	machinery					295:303	the N-glycosylation machinery	275:303	the N-glycosylation machinery in the endoplasmic reticulum and Golgi	275:342	By altering the N-glycosylation machinery in the endoplasmic reticulum and Golgi, proinflammatory cytokines promote the modification of endothelial glycoproteins such as vascular endothelial growth factor receptor 2 (VEGFR2) with sialic acid-capped N-glycans.
31308178	4	75	from	signaling	897:905	arg1	cells					922:926	endothelial cells	910:926	endothelial cells	910:926	Here, using glycoside hydrolase and kinase assays and immunoprecipitation and MS-based analyses, we demonstrate that N-linked glycans at the Asn-247 site in VEGFR2 hinder VEGF ligand-mediated receptor activation and signaling in endothelial cells.
31308178	1	76	theme	proinflammatory	158:172	arg1	signals					174:180	proinflammatory signals	158:180	proinflammatory signals	158:180	The tumor microenvironment and proinflammatory signals significantly alter glycosylation of cell-surface proteins on endothelial cells.
31308178	3	77	from	signaling	609:617	arg1	contexts					653:660	physiological and pathological contexts	622:660	physiological and pathological contexts	622:660	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
31308178	3	77	from	signaling	609:617	arg1	cancer					673:678	cancer	673:678	cancer	673:678	VEGFR2 is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer.
30143116	5	0	theme	GC-MS	921:925	arg1	analyses					927:934	GC-MS analyses	921:934	GC-MS analyses	921:934	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	1	1	theme	size	368:371	arg1	chromatography					383:396	size exclusion chromatography	368:396	size exclusion chromatography	368:396	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	1	2	with	extraction	239:248	arg1	water					263:267	boiling water	255:267	boiling water followed by deproteination	255:294	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	1	3	theme	water	165:169	arg1	extract					171:177	water extract	165:177	water extract	165:177	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	0	4	theme	Quinine	82:88	arg1	bodies					72:77	fruit bodies	66:77	fruit bodies of Quinine	66:88	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine conk Fomitopsis officinalis.
30143116	1	5	theme	exclusion	373:381	arg1	chromatography					383:396	size exclusion chromatography	368:396	size exclusion chromatography	368:396	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	1	6	theme	extract	171:177	arg1	component					152:160	a major component	144:160	a major component of water extract	144:177	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	4	7	theme	β-D-galactopyranosyl	814:833	arg1	residues					835:842	3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues	769:842	3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues	769:842	Almost every second residue in the backbone was substituted at O-2 by 3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues.
30143116	0	8	theme	Fomitopsis	95:104	arg1	officinalis					106:116	Fomitopsis officinalis	95:116	Fomitopsis officinalis	95:116	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine conk Fomitopsis officinalis.
30143116	3	9	with	mannofucogalactan	584:600	arg1	backbone					609:616	a backbone	607:616	a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	607:696	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	1	10	with	purification	315:326	arg1	water					263:267	boiling water	255:267	boiling water followed by deproteination	255:294	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	5	11	theme	chains	987:992	arg1	part					956:959	the part	952:959	the part of mannofucogalactan side chains	952:992	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	5	11	theme	chains	987:992	arg1	units					889:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	2	12	theme	one-	499:502	arg1	composition					464:474	monosaccharide composition	449:474	monosaccharide composition	449:474	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	2	12	theme	one-	499:502	arg1	spectroscopy					528:539	one- and two-dimensional NMR spectroscopy	499:539	one- and two-dimensional NMR spectroscopy	499:539	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	3	13	link	1,6-O-linked	655:666	arg1	residues					689:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	0	14	attach	isolated	52:59	arg1	bodies					72:77	fruit bodies	66:77	fruit bodies of Quinine	66:88	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine conk Fomitopsis officinalis.
30143116	0	14	attach	isolated	52:59	arg2	mannofucogalactan					34:50	the mannofucogalactan	30:50	the mannofucogalactan isolated from fruit bodies of Quinine	30:88	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine conk Fomitopsis officinalis.
30143116	3	15	theme	3-O-methylated	640:653	arg1	residues					689:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	4	16	theme	3-O-α-D-mannopyranosyl-α-L-fucopyranosyl	769:808	arg1	residues					835:842	3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues	769:842	3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues	769:842	Almost every second residue in the backbone was substituted at O-2 by 3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues.
30143116	0	17	theme	Structure	0:8	arg1	characterization					10:25	Structure characterization	0:25	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine	0:88	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine conk Fomitopsis officinalis.
30143116	3	18	theme	1,6-O-linked	655:666	arg1	residues					689:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	1	19	theme	fruit	197:201	arg1	bodies					203:208	fruit bodies	197:208	fruit bodies of Fomitopsis officinalis	197:234	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	1	20	with	decoloration	297:308	arg1	water					263:267	boiling water	255:267	boiling water followed by deproteination	255:294	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	5	21	theme	side	982:985	arg1	chains					987:992	mannofucogalactan side chains	964:992	mannofucogalactan side chains	964:992	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	2	22	theme	methylation	477:487	arg1	composition					464:474	monosaccharide composition	449:474	monosaccharide composition	449:474	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	2	22	theme	methylation	477:487	arg1	analysis					489:496	methylation analysis	477:496	methylation analysis	477:496	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	5	23	theme	non-reducing	849:860	arg1	part					956:959	the part	952:959	the part of mannofucogalactan side chains	952:992	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	5	23	theme	non-reducing	849:860	arg1	units					889:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	2	24	theme	composition	464:474	arg1	data					441:444	the data	437:444	the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy	437:539	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	5	25	theme	terminal	862:869	arg1	part					956:959	the part	952:959	the part of mannofucogalactan side chains	952:992	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	5	25	theme	terminal	862:869	arg1	units					889:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	1	26	theme	Fomitopsis	213:222	arg1	officinalis					224:234	Fomitopsis officinalis	213:234	Fomitopsis officinalis	213:234	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	2	27	theme	monosaccharide	449:462	arg1	composition					464:474	monosaccharide composition	449:474	monosaccharide composition	449:474	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	2	27	theme	monosaccharide	449:462	arg1	analysis					489:496	methylation analysis	477:496	methylation analysis	477:496	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	2	27	theme	monosaccharide	449:462	arg1	spectroscopy					528:539	one- and two-dimensional NMR spectroscopy	499:539	one- and two-dimensional NMR spectroscopy	499:539	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	0	28	theme	mannofucogalactan	34:50	arg1	characterization					10:25	Structure characterization	0:25	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine	0:88	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine conk Fomitopsis officinalis.
30143116	2	29	theme	NMR	524:526	arg1	composition					464:474	monosaccharide composition	449:474	monosaccharide composition	449:474	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	2	29	theme	NMR	524:526	arg1	spectroscopy					528:539	one- and two-dimensional NMR spectroscopy	499:539	one- and two-dimensional NMR spectroscopy	499:539	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	1	30	theme	officinalis	224:234	arg1	bodies					203:208	fruit bodies	197:208	fruit bodies of Fomitopsis officinalis	197:234	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	0	31	theme	fruit	66:70	arg1	bodies					72:77	fruit bodies	66:77	fruit bodies of Quinine	66:88	Structure characterization of the mannofucogalactan isolated from fruit bodies of Quinine conk Fomitopsis officinalis.
30143116	4	32	from	residue	719:725	arg1	backbone					734:741	the backbone	730:741	the backbone	730:741	Almost every second residue in the backbone was substituted at O-2 by 3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues.
30143116	3	33	theme	α-D-galactopyranosyl	668:687	arg1	residues					689:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	630:696	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	3	34	theme	studied	546:552	arg1	polysaccharide					554:567	The studied polysaccharide	542:567	The studied polysaccharide	542:567	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	3	34	theme	studied	546:552	arg1	mannofucogalactan					584:600	a branched mannofucogalactan	573:600	a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	573:696	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	5	35	theme	α-L-fucopyranosyl	871:887	arg1	part					956:959	the part	952:959	the part of mannofucogalactan side chains	952:992	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	5	35	theme	α-L-fucopyranosyl	871:887	arg1	units					889:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units	845:893	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	1	36	theme	anion-exchange	334:347	arg1	chromatography					349:362	anion-exchange chromatography	334:362	anion-exchange chromatography	334:362	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	4	37	theme	second	712:717	arg1	residue					719:725	Almost every second residue	699:725	Almost every second residue in the backbone	699:741	Almost every second residue in the backbone was substituted at O-2 by 3-O-α-D-mannopyranosyl-α-L-fucopyranosyl and β-D-galactopyranosyl residues.
30143116	1	38	theme	major	146:150	arg1	component					152:160	a major component	144:160	a major component of water extract	144:177	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
30143116	3	39	theme	branched	575:582	arg1	polysaccharide					554:567	The studied polysaccharide	542:567	The studied polysaccharide	542:567	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	3	39	theme	branched	575:582	arg1	mannofucogalactan					584:600	a branched mannofucogalactan	573:600	a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues	573:696	The studied polysaccharide was a branched mannofucogalactan with a backbone composed of partially 3-O-methylated 1,6-O-linked α-D-galactopyranosyl residues.
30143116	2	40	theme	two-dimensional	508:522	arg1	composition					464:474	monosaccharide composition	449:474	monosaccharide composition	449:474	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	2	40	theme	two-dimensional	508:522	arg1	spectroscopy					528:539	one- and two-dimensional NMR spectroscopy	499:539	one- and two-dimensional NMR spectroscopy	499:539	Its structure was characterized using the data of monosaccharide composition, methylation analysis, one- and two-dimensional NMR spectroscopy.
30143116	5	41	theme	mannofucogalactan	964:980	arg1	chains					987:992	mannofucogalactan side chains	964:992	mannofucogalactan side chains	964:992	The non-reducing terminal α-L-fucopyranosyl units, which were identified by GC-MS analyses, appeared to be the part of mannofucogalactan side chains also.
30143116	1	42	theme	boiling	255:261	arg1	water					263:267	boiling water	255:267	boiling water followed by deproteination	255:294	The mannofucogalactan as a major component of water extract was obtained from fruit bodies of Fomitopsis officinalis by extraction with boiling water followed by deproteination, decoloration, and purification using anion-exchange chromatography and size exclusion chromatography.
29465778	0	0	theme	factor	96:101	arg1	HOXA1					103:107	the transcription factor HOXA1	78:107	the transcription factor HOXA1	78:107	The O-GlcNAc transferase OGT interacts with and post-translationally modifies the transcription factor HOXA1.
29465778	3	1	theme	partner	324:330	arg1	proteins					332:339	distinct partner proteins	315:339	distinct partner proteins interacting with HOXA1	315:362	Recent data from our group revealed distinct partner proteins interacting with HOXA1.
29465778	1	2	theme	factors	159:165	arg1	family					135:140	the HOX family	127:140	the HOX family of transcription factors which are key regulators of animal development	127:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	0	3	theme	transcription	82:94	arg1	HOXA1					103:107	the transcription factor HOXA1	78:107	the transcription factor HOXA1	78:107	The O-GlcNAc transferase OGT interacts with and post-translationally modifies the transcription factor HOXA1.
29465778	4	4	theme	N-acetylglucosamine	396:414	arg1	transferase					427:437	an O-linked N-acetylglucosamine (O-GlcNAc) transferase	384:437	an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription	384:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	4	4	theme	N-acetylglucosamine	396:414	arg1	OGT					377:379	OGT	377:379	OGT	377:379	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	6	5	theme	O-GlcNAc	909:916	arg1	group					918:922	an O-GlcNAc group	906:922	an O-GlcNAc group	906:922	Mass spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is replaced by an O-GlcNAc group.
29465778	4	6	theme	O-linked	387:394	arg1	N-acetylglucosamine					396:414	O-linked N-acetylglucosamine	387:414	an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription	384:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	4	6	theme	O-linked	387:394	arg1	O-GlcNAc					417:424	O-GlcNAc	417:424	O-GlcNAc	417:424	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	4	7	theme	different	483:491	arg1	transcription					522:534	transcription	522:534	transcription	522:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	4	7	theme	different	483:491	arg1	processes					502:510	different cellular processes	483:510	different cellular processes including transcription	483:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	5	8	theme	HOXA1	614:618	arg1	OGT					624:626	OGT	624:626	OGT	624:626	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	5	8	theme	HOXA1	614:618	arg1	HOXA1					614:618	HOXA1	614:618	HOXA1	614:618	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	5	8	theme	HOXA1	614:618	arg1	domains					603:609	domains	603:609	domains of HOXA1 and OGT	603:626	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	5	9	theme	OGT	624:626	arg1	OGT					624:626	OGT	624:626	OGT	624:626	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	5	9	theme	OGT	624:626	arg1	HOXA1					614:618	HOXA1	614:618	HOXA1	614:618	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	5	9	theme	OGT	624:626	arg1	domains					603:609	domains	603:609	domains of HOXA1 and OGT	603:626	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	1	10	theme	key	177:179	arg1	regulators					181:190	key regulators	177:190	key regulators of animal development	177:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	1	10	theme	key	177:179	arg1	factors					159:165	transcription factors	145:165	transcription factors which are key regulators of animal development	145:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	0	11	theme	O-GlcNAc	4:11	arg1	transferase					13:23	The O-GlcNAc transferase	0:23	The O-GlcNAc transferase OGT	0:27	The O-GlcNAc transferase OGT interacts with and post-translationally modifies the transcription factor HOXA1.
29465778	4	12	theme	cellular	493:500	arg1	transcription					522:534	transcription	522:534	transcription	522:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	4	12	theme	cellular	493:500	arg1	processes					502:510	different cellular processes	483:510	different cellular processes including transcription	483:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	1	13	theme	animal	195:200	arg1	development					202:212	animal development	195:212	animal development	195:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	0	14	theme	transferase	13:23	arg1	OGT					25:27	The O-GlcNAc transferase OGT	0:27	The O-GlcNAc transferase OGT	0:27	The O-GlcNAc transferase OGT interacts with and post-translationally modifies the transcription factor HOXA1.
29465778	1	15	theme	development	202:212	arg1	regulators					181:190	key regulators	177:190	key regulators of animal development	177:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	1	15	theme	development	202:212	arg1	factors					159:165	transcription factors	145:165	transcription factors which are key regulators of animal development	145:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	5	16	dep	required	632:639	arg1	which					597:601	which	597:601	which	597:601	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	6	17	theme	phosphate	874:882	arg1	adduct					884:889	the phosphate adduct	870:889	the phosphate adduct	870:889	Mass spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is replaced by an O-GlcNAc group.
29465778	3	18	theme	Recent	279:284	arg1	data					286:289	Recent data	279:289	Recent data from our group	279:304	Recent data from our group revealed distinct partner proteins interacting with HOXA1.
29465778	6	19	theme	AGGTVGSPQYIHHSY	816:830	arg1	peptide					832:838	the AGGTVGSPQYIHHSY peptide	812:838	the AGGTVGSPQYIHHSY peptide	812:838	Mass spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is replaced by an O-GlcNAc group.
29465778	4	20	theme	proteins	462:469	arg1	proteins					462:469	proteins	462:469	proteins involved in different cellular processes including transcription	462:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	4	20	theme	proteins	462:469	arg1	variety					451:457	a variety	449:457	a variety of proteins involved in different cellular processes including transcription	449:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	3	21	theme	distinct	315:322	arg1	proteins					332:339	distinct partner proteins	315:339	distinct partner proteins interacting with HOXA1	315:362	Recent data from our group revealed distinct partner proteins interacting with HOXA1.
29465778	5	22	theme	HOXA1	563:567	arg1	OGT					554:556	OGT	554:556	OGT	554:556	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	5	22	theme	HOXA1	563:567	arg1	interactor					569:578	a HOXA1 interactor	561:578	a HOXA1 interactor	561:578	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	6	23	theme	OGT	854:856	arg1	expression					858:867	OGT expression	854:867	OGT expression	854:867	Mass spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is replaced by an O-GlcNAc group.
29465778	1	24	theme	HOX	131:133	arg1	family					135:140	the HOX family	127:140	the HOX family of transcription factors which are key regulators of animal development	127:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	3	25	from	group	300:304	arg1	data					286:289	Recent data	279:289	Recent data from our group	279:304	Recent data from our group revealed distinct partner proteins interacting with HOXA1.
29465778	6	26	theme	spectrometry	737:748	arg1	experiments					750:760	Mass spectrometry experiments	732:760	Mass spectrometry experiments	732:760	Mass spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is replaced by an O-GlcNAc group.
29465778	4	27	link	O-linked	387:394	arg1	N-acetylglucosamine					396:414	O-linked N-acetylglucosamine	387:414	an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription	384:534	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	4	27	link	O-linked	387:394	arg1	O-GlcNAc					417:424	O-GlcNAc	417:424	O-GlcNAc	417:424	Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription.
29465778	2	28	theme	molecular	241:249	arg1	pathways					251:258	the molecular pathways	237:258	the molecular pathways controlling HOXA1	237:276	Little is known about the molecular pathways controlling HOXA1.
29465778	6	29	theme	Mass	732:735	arg1	spectrometry					737:748	Mass spectrometry	732:748	Mass spectrometry experiments	732:760	Mass spectrometry experiments indeed reveal that HOXA1 can be phosphorylated on the AGGTVGSPQYIHHSY peptide and that upon OGT expression, the phosphate adduct is replaced by an O-GlcNAc group.
29465778	1	30	theme	transcription	145:157	arg1	regulators					181:190	key regulators	177:190	key regulators of animal development	177:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	1	30	theme	transcription	145:157	arg1	factors					159:165	transcription factors	145:165	transcription factors which are key regulators of animal development	145:212	HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development.
29465778	5	31	dep	characterise	584:595	arg1	required					632:639	required	632:639	are required for the interaction	628:659	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
29465778	5	31	dep	characterise	584:595	arg1	provide					669:675	provide	669:675	provide evidence that OGT post-translationally modifies HOXA1	669:729	Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1.
30149081	5	0	theme	agglutination	796:808	arg1	activities					810:819	agglutination activities	796:819	agglutination activities	796:819	rHEL2a and rHEL2b exhibited agglutination activities, but rHEL1 did not show any agglutination activity toward animal erythrocytes.
30149081	8	1	theme	glycan	1213:1218	arg1	comparable					1267:1276	comparable	1267:1276	comparable	1267:1276	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	1	theme	glycan	1213:1218	arg1	specificities					1228:1240	the glycan binding specificities	1209:1240	the glycan binding specificities of rHEL2 isolectins	1209:1260	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	7	2	theme	titration	1057:1065	arg1	calorimetry					1067:1077	isothermal titration calorimetry	1046:1077	isothermal titration calorimetry	1046:1077	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	1	3	theme	mushroom	170:177	arg1	body					188:191	Hericium erinaceus mushroom fruiting body	151:191	Hericium erinaceus mushroom fruiting body	151:191	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	6	4	gly	glycoproteins	973:985	arg1	glycoproteins					973:985	glycoproteins	973:985	glycoproteins containing mucin-type O-glycans	973:1017	The hemagglutination activity of rHEL2 lectins was strongly inhibited by glycoproteins containing mucin-type O-glycans.
30149081	7	5	theme	O-glycan	1166:1173	arg1	motif					1175:1179	the core 1 O-glycan motif	1155:1179	the core 1 O-glycan motif	1155:1179	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	1	6	theme	RNA-Seq	351:357	arg1	data					359:362	RNA-Seq data	351:362	RNA-Seq data	351:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	1	7	theme	fruiting	179:186	arg1	body					188:191	Hericium erinaceus mushroom fruiting body	151:191	Hericium erinaceus mushroom fruiting body	151:191	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	9	8	theme	cells	1606:1610	arg1	surface					1588:1594	the surface	1584:1594	the surface of cancer cells	1584:1610	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	7	9	theme	1,3	1187:1189	arg1	O-glycans					1135:1143	O-glycans	1135:1143	O-glycans harboring the core 1 O-glycan motif	1135:1179	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	7	9	theme	1,3	1187:1189	arg1	GalNAc					1191:1196	Galβ(1,3)GalNAc	1182:1196	Galβ(1,3)GalNAc	1182:1196	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	8	10	theme	K562	1431:1434	arg1	cells					1451:1455	K562 human leukemia cells	1431:1455	K562 human leukemia cells	1431:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	11	theme	binding	1220:1226	arg1	comparable					1267:1276	comparable	1267:1276	comparable	1267:1276	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	11	theme	binding	1220:1226	arg1	specificities					1228:1240	the glycan binding specificities	1209:1240	the glycan binding specificities of rHEL2 isolectins	1209:1260	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	7	12	theme	Glycan	1020:1025	arg1	analysis					1033:1040	Glycan array analysis	1020:1040	Glycan array analysis	1020:1040	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	1	13	theme	peptide	263:269	arg1	fingerprinting					276:289	peptide mass fingerprinting	263:289	peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data	263:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	0	14	theme	human	126:130	arg1	cells					141:145	K562 human leukemia cells	121:145	K562 human leukemia cells	121:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	6	15	theme	lectins	939:945	arg1	activity					921:928	The hemagglutination activity	900:928	The hemagglutination activity of rHEL2 lectins	900:945	The hemagglutination activity of rHEL2 lectins was strongly inhibited by glycoproteins containing mucin-type O-glycans.
30149081	7	16	theme	Galβ	1182:1185	arg1	O-glycans					1135:1143	O-glycans	1135:1143	O-glycans harboring the core 1 O-glycan motif	1135:1179	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	7	16	theme	Galβ	1182:1185	arg1	GalNAc					1191:1196	Galβ(1,3)GalNAc	1182:1196	Galβ(1,3)GalNAc	1182:1196	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	7	17	theme	array	1027:1031	arg1	analysis					1033:1040	Glycan array analysis	1020:1040	Glycan array analysis	1020:1040	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	3	18	theme	soluble	536:542	arg1	proteins					544:551	fully active soluble proteins	523:551	fully active soluble proteins designated rHEL1, rHEL2a, and rHEL2b	523:588	Codon-optimized genes encoding HEL1, HEL2a, and HEL2b were expressed in Escherichia coli to produce fully active soluble proteins designated rHEL1, rHEL2a, and rHEL2b.
30149081	0	19	theme	K562	121:124	arg1	cells					141:145	K562 human leukemia cells	121:145	K562 human leukemia cells	121:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	6	20	theme	rHEL2	933:937	arg1	lectins					939:945	rHEL2 lectins	933:945	rHEL2 lectins	933:945	The hemagglutination activity of rHEL2 lectins was strongly inhibited by glycoproteins containing mucin-type O-glycans.
30149081	9	21	theme	cancer	1599:1604	arg1	cells					1606:1610	cancer cells	1599:1610	cancer cells	1599:1610	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	8	22	theme	isolectins	1251:1260	arg1	comparable					1267:1276	comparable	1267:1276	comparable	1267:1276	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	22	theme	isolectins	1251:1260	arg1	specificities					1228:1240	the glycan binding specificities	1209:1240	the glycan binding specificities of rHEL2 isolectins	1209:1260	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	6	23	theme	mucin-type	998:1007	arg1	O-glycans					1009:1017	mucin-type O-glycans	998:1017	mucin-type O-glycans	998:1017	The hemagglutination activity of rHEL2 lectins was strongly inhibited by glycoproteins containing mucin-type O-glycans.
30149081	0	24	theme	erinaceus	9:17	arg1	isolectins					19:28	Hericium erinaceus isolectins	0:28	Hericium erinaceus isolectins	0:28	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	3	25	theme	active	529:534	arg1	proteins					544:551	fully active soluble proteins	523:551	fully active soluble proteins designated rHEL1, rHEL2a, and rHEL2b	523:588	Codon-optimized genes encoding HEL1, HEL2a, and HEL2b were expressed in Escherichia coli to produce fully active soluble proteins designated rHEL1, rHEL2a, and rHEL2b.
30149081	8	26	attach	attached	1347:1354	arg2	O-glycans					1337:1345	O-glycans	1337:1345	O-glycans attached to leukosialin	1337:1369	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	26	attach	attached	1347:1354	arg1	leukosialin					1359:1369	leukosialin	1359:1369	leukosialin	1359:1369	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	26	attach	attached	1347:1354	arg2	antigens					1404:1411	tumor-associated carbohydrate antigens	1374:1411	tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	1374:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	9	27	theme	mucin-type	1550:1559	arg1	O-glycans					1561:1569	mucin-type O-glycans	1550:1569	mucin-type O-glycans expressed on the surface of cancer cells	1550:1610	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	0	28	theme	Hericium	0:7	arg1	isolectins					19:28	Hericium erinaceus isolectins	0:28	Hericium erinaceus isolectins	0:28	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	1	29	theme	mass	271:274	arg1	fingerprinting					276:289	peptide mass fingerprinting	263:289	peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data	263:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	8	30	theme	cells	1451:1455	arg1	surface					1420:1426	the surface	1416:1426	the surface of K562 human leukemia cells	1416:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	31	theme	leukemia	1442:1449	arg1	cells					1451:1455	K562 human leukemia cells	1431:1455	K562 human leukemia cells	1431:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	1	32	theme	different	198:206	arg1	groups					215:220	two different lectin groups	194:220	two different lectin groups	194:220	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	1	32	theme	different	198:206	arg1	HEL2					232:235	HEL2	232:235	HEL2	232:235	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	1	32	theme	different	198:206	arg1	HEL1					223:226	HEL1	223:226	HEL1	223:226	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	0	33	theme	cells	141:145	arg1	surface					110:116	the surface	106:116	the surface of K562 human leukemia cells	106:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	34	from	antigens	1404:1411	arg1	surface					1420:1426	the surface	1416:1426	the surface of K562 human leukemia cells	1416:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	1	35	theme	lectin	208:213	arg1	groups					215:220	two different lectin groups	194:220	two different lectin groups	194:220	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	1	35	theme	lectin	208:213	arg1	HEL2					232:235	HEL2	232:235	HEL2	232:235	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	1	35	theme	lectin	208:213	arg1	HEL1					223:226	HEL1	223:226	HEL1	223:226	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	5	36	theme	agglutination	849:861	arg1	activity					863:870	any agglutination activity	845:870	any agglutination activity toward animal erythrocytes	845:897	rHEL2a and rHEL2b exhibited agglutination activities, but rHEL1 did not show any agglutination activity toward animal erythrocytes.
30149081	0	37	theme	leukemia	132:139	arg1	cells					141:145	K562 human leukemia cells	121:145	K562 human leukemia cells	121:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	38	from	comparable	1267:1276	arg1	ability					1316:1322	their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	1310:1455	their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	1310:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	4	39	theme	molecular	637:645	arg1	weights					647:653	different molecular weights	627:653	different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b	627:733	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	4	39	theme	molecular	637:645	arg1	15 kDa					670:675	15 kDa	670:675	15 kDa	670:675	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	4	39	theme	molecular	637:645	arg1	120 kDa					705:711	120 kDa	705:711	120 kDa	705:711	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	3	40	theme	Codon-optimized	423:437	arg1	genes					439:443	Codon-optimized genes	423:443	Codon-optimized genes encoding HEL1, HEL2a, and HEL2b	423:475	Codon-optimized genes encoding HEL1, HEL2a, and HEL2b were expressed in Escherichia coli to produce fully active soluble proteins designated rHEL1, rHEL2a, and rHEL2b.
30149081	6	41	theme	hemagglutination	904:919	arg1	activity					921:928	The hemagglutination activity	900:928	The hemagglutination activity of rHEL2 lectins	900:945	The hemagglutination activity of rHEL2 lectins was strongly inhibited by glycoproteins containing mucin-type O-glycans.
30149081	5	42	theme	animal	879:884	arg1	erythrocytes					886:897	animal erythrocytes	879:897	animal erythrocytes	879:897	rHEL2a and rHEL2b exhibited agglutination activities, but rHEL1 did not show any agglutination activity toward animal erythrocytes.
30149081	0	43	theme	mucin-type	40:49	arg1	O-glycans					51:59	mucin-type O-glycans	40:59	mucin-type O-glycans	40:59	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	0	43	theme	mucin-type	40:49	arg1	antigens					94:101	tumor-associated carbohydrate antigens	64:101	tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	64:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	1	44	theme	customized	300:309	arg1	databases					328:336	customized protein sequence databases	300:336	customized protein sequence databases derived from RNA-Seq data	300:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	7	45	theme	core	1159:1162	arg1	motif					1175:1179	the core 1 O-glycan motif	1155:1179	the core 1 O-glycan motif	1155:1179	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	0	46	from	antigens	94:101	arg1	surface					110:116	the surface	106:116	the surface of K562 human leukemia cells	106:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	9	47	theme	rHEL2	1486:1490	arg1	tool					1531:1534	a powerful tool	1520:1534	a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells	1520:1610	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	9	47	theme	rHEL2	1486:1490	arg1	isolectins					1492:1501	rHEL2 isolectins	1486:1501	rHEL2 isolectins	1486:1501	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	8	48	theme	tumor-associated	1374:1389	arg1	O-glycans					1337:1345	O-glycans	1337:1345	O-glycans attached to leukosialin	1337:1369	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	48	theme	tumor-associated	1374:1389	arg1	antigens					1404:1411	tumor-associated carbohydrate antigens	1374:1411	tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	1374:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	0	49	theme	tumor-associated	64:79	arg1	O-glycans					51:59	mucin-type O-glycans	40:59	mucin-type O-glycans	40:59	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	0	49	theme	tumor-associated	64:79	arg1	antigens					94:101	tumor-associated carbohydrate antigens	64:101	tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	64:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	1	50	theme	protein	311:317	arg1	databases					328:336	customized protein sequence databases	300:336	customized protein sequence databases derived from RNA-Seq data	300:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	9	51	used	used	1512:1515	arg2	isolectins					1492:1501	rHEL2 isolectins	1486:1501	rHEL2 isolectins	1486:1501	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	9	51	used	used	1512:1515	arg2	tool					1531:1534	a powerful tool	1520:1534	a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells	1520:1610	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	4	52	dep	weights	647:653	arg1	120 kDa					705:711	120 kDa	705:711	120 kDa	705:711	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	4	52	dep	weights	647:653	arg1	15 kDa					670:675	15 kDa	670:675	15 kDa	670:675	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	4	52	dep	weights	647:653	arg1	weights					647:653	different molecular weights	627:653	different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b	627:733	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	8	53	from	ability	1316:1322	arg1	comparable					1267:1276	comparable	1267:1276	comparable	1267:1276	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	53	from	ability	1316:1322	arg1	specificities					1228:1240	the glycan binding specificities	1209:1240	the glycan binding specificities of rHEL2 isolectins	1209:1260	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	54	theme	peanut	1289:1294	arg1	agglutinin					1296:1305	peanut agglutinin	1289:1305	peanut agglutinin	1289:1305	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	1	55	theme	sequence	319:326	arg1	databases					328:336	customized protein sequence databases	300:336	customized protein sequence databases derived from RNA-Seq data	300:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	1	56	attach	derived	338:344	arg2	databases					328:336	customized protein sequence databases	300:336	customized protein sequence databases derived from RNA-Seq data	300:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	1	56	attach	derived	338:344	arg1	data					359:362	RNA-Seq data	351:362	RNA-Seq data	351:362	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	6	57	contain	containing	987:996	arg2	O-glycans					1009:1017	mucin-type O-glycans	998:1017	mucin-type O-glycans	998:1017	The hemagglutination activity of rHEL2 lectins was strongly inhibited by glycoproteins containing mucin-type O-glycans.
30149081	6	57	contain	containing	987:996	arg1	glycoproteins					973:985	glycoproteins	973:985	glycoproteins containing mucin-type O-glycans	973:1017	The hemagglutination activity of rHEL2 lectins was strongly inhibited by glycoproteins containing mucin-type O-glycans.
30149081	7	58	theme	rHEL2	1093:1097	arg1	isolectins					1099:1108	rHEL2 isolectins	1093:1108	rHEL2 isolectins	1093:1108	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	4	59	theme	non-denaturing	741:754	arg1	conditions					756:765	non-denaturing conditions	741:765	non-denaturing conditions	741:765	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	8	60	theme	human	1436:1440	arg1	cells					1451:1455	K562 human leukemia cells	1431:1455	K562 human leukemia cells	1431:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	2	61	theme	HEL2	369:372	arg1	group					374:378	The HEL2 group	365:378	The HEL2 group	365:378	The HEL2 group included four isoforms designated HEL2a-d.
30149081	8	62	theme	carbohydrate	1391:1402	arg1	O-glycans					1337:1345	O-glycans	1337:1345	O-glycans attached to leukosialin	1337:1369	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	62	theme	carbohydrate	1391:1402	arg1	antigens					1404:1411	tumor-associated carbohydrate antigens	1374:1411	tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	1374:1455	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	8	63	theme	rHEL2	1245:1249	arg1	isolectins					1251:1260	rHEL2 isolectins	1245:1260	rHEL2 isolectins	1245:1260	Moreover, the glycan binding specificities of rHEL2 isolectins were comparable to that of peanut agglutinin in their ability to recognize O-glycans attached to leukosialin as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	1	64	theme	Hericium	151:158	arg1	body					188:191	Hericium erinaceus mushroom fruiting body	151:191	Hericium erinaceus mushroom fruiting body	151:191	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
30149081	9	65	theme	powerful	1522:1529	arg1	tool					1531:1534	a powerful tool	1520:1534	a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells	1520:1610	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	9	65	theme	powerful	1522:1529	arg1	isolectins					1492:1501	rHEL2 isolectins	1486:1501	rHEL2 isolectins	1486:1501	These results indicate that rHEL2 isolectins could be used as a powerful tool for analyzing mucin-type O-glycans expressed on the surface of cancer cells.
30149081	4	66	theme	different	627:635	arg1	weights					647:653	different molecular weights	627:653	different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b	627:733	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	4	66	theme	different	627:635	arg1	15 kDa					670:675	15 kDa	670:675	15 kDa	670:675	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	4	66	theme	different	627:635	arg1	120 kDa					705:711	120 kDa	705:711	120 kDa	705:711	Interestingly, these lectins showed different molecular weights: approximately 15 kDa for rHEL1 and approximately 120 kDa for rHEL2a and rHEL2b under non-denaturing conditions.
30149081	0	67	theme	carbohydrate	81:92	arg1	O-glycans					51:59	mucin-type O-glycans	40:59	mucin-type O-glycans	40:59	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	0	67	theme	carbohydrate	81:92	arg1	antigens					94:101	tumor-associated carbohydrate antigens	64:101	tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells	64:145	Hericium erinaceus isolectins recognize mucin-type O-glycans as tumor-associated carbohydrate antigens on the surface of K562 human leukemia cells.
30149081	7	68	theme	isothermal	1046:1055	arg1	calorimetry					1067:1077	isothermal titration calorimetry	1046:1077	isothermal titration calorimetry	1046:1077	Glycan array analysis and isothermal titration calorimetry revealed that rHEL2 isolectins interacted strongly with O-glycans harboring the core 1 O-glycan motif, Galβ(1,3)GalNAc.
30149081	1	69	theme	erinaceus	160:168	arg1	body					188:191	Hericium erinaceus mushroom fruiting body	151:191	Hericium erinaceus mushroom fruiting body	151:191	In Hericium erinaceus mushroom fruiting body, two different lectin groups, HEL1 and HEL2, were identified by using peptide mass fingerprinting based on customized protein sequence databases derived from RNA-Seq data.
29530619	8	0	theme	O-GlcNAc-modified	1180:1196	arg1	levels					1205:1210	the O-GlcNAc-modified Nav1.5 levels	1176:1210	the O-GlcNAc-modified Nav1.5 levels	1176:1210	In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97.
29530619	9	1	from	measurements	1325:1336	arg1	cells					1351:1355	HEK-293 T cells	1341:1355	HEK-293 T cells	1341:1355	Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.
29530619	11	2	theme	arrhythmogenesis	1960:1975	arg1	development					1941:1951	the development	1937:1951	the development of the arrhythmogenesis in DH	1937:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	3	mod	modification	1835:1846	arg1	Nav1.5					1851:1856	Nav1.5	1851:1856	Nav1.5	1851:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	3	mod	modification	1835:1846	arg3	O-GlcNAc					1826:1833	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	6	4	theme	increased	874:882	arg1	susceptibility					884:897	increased susceptibility	874:897	increased susceptibility to ventricular arrhythmias	874:924	STZ-induced 3-month diabetic rats displayed increased susceptibility to ventricular arrhythmias.
29530619	2	5	theme	ventricular	274:284	arg1	arrhythmias					286:296	ventricular arrhythmias	274:296	ventricular arrhythmias	274:296	The mechanisms underlying the progression of diabetic heart (DH) to ventricular arrhythmias are unclear.
29530619	1	6	theme	diabetic	187:194	arg1	patients					196:203	diabetic patients	187:203	diabetic patients	187:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	10	7	theme	abnormal	1688:1695	arg1	expression					1697:1706	abnormal expression	1688:1706	abnormal expression	1688:1706	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	8	theme	interval	1806:1813	arg1	prolongation					1780:1791	prolongation	1780:1791	prolongation of the PR/QT interval	1780:1813	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	8	theme	interval	1806:1813	arg1	distribution					1712:1723	distribution	1712:1723	distribution	1712:1723	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	8	theme	interval	1806:1813	arg1	expression					1697:1706	abnormal expression	1688:1706	abnormal expression	1688:1706	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	8	theme	interval	1806:1813	arg1	loss					1736:1739	loss	1736:1739	loss of function of the sodium channel	1736:1773	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	8	9	theme	Nav1.5-binding	1260:1273	arg1	proteins					1275:1282	Nav1.5-binding proteins	1260:1282	Nav1.5-binding proteins	1260:1282	In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97.
29530619	11	10	theme	contributing	1913:1924	arg1	modification					1835:1846	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	10	theme	contributing	1913:1924	arg1	event					1879:1883	a novel signaling event	1861:1883	a novel signaling event	1861:1883	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	10	theme	contributing	1913:1924	arg1	factor					1926:1931	an underlying contributing factor	1899:1931	an underlying contributing factor for the development of the arrhythmogenesis in DH	1899:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	2	11	theme	diabetic	251:258	arg1	DH					267:268	DH	267:268	DH	267:268	The mechanisms underlying the progression of diabetic heart (DH) to ventricular arrhythmias are unclear.
29530619	2	11	theme	diabetic	251:258	arg1	heart					260:264	diabetic heart	251:264	diabetic heart (DH)	251:269	The mechanisms underlying the progression of diabetic heart (DH) to ventricular arrhythmias are unclear.
29530619	5	12	theme	diabetes	820:827	arg1	model					811:815	a rat model	805:815	a rat model of diabetes	805:827	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	5	13	theme	Sprague-Dawley	684:697	arg1	rats					699:702	Sprague-Dawley rats	684:702	Sprague-Dawley rats (male, 200-230 g)	684:720	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	7	14	theme	cytoplasmic	1010:1020	arg1	expression					1029:1038	both total and cytoplasmic Nav1.5 expression	995:1038	both total and cytoplasmic Nav1.5 expression	995:1038	The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro.
29530619	11	15	theme	Nav1.5	1851:1856	arg1	modification					1835:1846	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	15	theme	Nav1.5	1851:1856	arg1	factor					1926:1931	an underlying contributing factor	1899:1931	an underlying contributing factor for the development of the arrhythmogenesis in DH	1899:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	15	theme	Nav1.5	1851:1856	arg1	event					1879:1883	a novel signaling event	1861:1883	a novel signaling event	1861:1883	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	9	16	theme	HEK-293 T	1341:1349	arg1	cells					1351:1355	HEK-293 T cells	1341:1355	HEK-293 T cells	1341:1355	Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.
29530619	7	17	theme	total	1000:1004	arg1	expression					1029:1038	both total and cytoplasmic Nav1.5 expression	995:1038	both total and cytoplasmic Nav1.5 expression	995:1038	The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro.
29530619	1	18	theme	mortality	160:168	arg1	complications					126:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	1	18	theme	mortality	160:168	arg1	causes					150:155	major causes	144:155	major causes of mortality and morbidity in diabetic patients	144:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	11	19	theme	signaling	1869:1877	arg1	modification					1835:1846	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	19	theme	signaling	1869:1877	arg1	factor					1926:1931	an underlying contributing factor	1899:1931	an underlying contributing factor for the development of the arrhythmogenesis in DH	1899:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	19	theme	signaling	1869:1877	arg1	event					1879:1883	a novel signaling event	1861:1883	a novel signaling event	1861:1883	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	5	20	theme	streptozotocin	762:775	arg1	high-dose					749:757	high-dose	749:757	high-dose	749:757	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	1	21	theme	morbidity	174:182	arg1	complications					126:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	1	21	theme	morbidity	174:182	arg1	causes					150:155	major causes	144:155	major causes of mortality and morbidity in diabetic patients	144:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	5	22	dep	rats	699:702	arg1	200-230 g					711:719	200-230 g	711:719	200-230 g	711:719	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	5	22	dep	rats	699:702	arg1	male					705:708	male	705:708	male	705:708	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	11	23	from	arrhythmogenesis	1960:1975	arg1	DH					1980:1981	DH	1980:1981	DH	1980:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	1	24	from	patients	196:203	arg1	complications					126:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	1	24	from	patients	196:203	arg1	causes					150:155	major causes	144:155	major causes of mortality and morbidity in diabetic patients	144:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	3	25	theme	reversible	350:359	arg1	GlcNAcylation					320:332	O-linked GlcNAcylation	311:332	O-linked GlcNAcylation (O-GlcNAc)	311:343	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	3	25	theme	reversible	350:359	arg1	modification					380:391	a reversible post-translational modification	348:391	a reversible post-translational modification for the regulation of diverse cellular processes	348:440	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	11	26	from	DH	1980:1981	arg1	development					1941:1951	the development	1937:1951	the development of the arrhythmogenesis in DH	1937:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	7	27	theme	O-GlcNAc	940:947	arg1	modification					949:960	The elevated O-GlcNAc modification	927:960	The elevated O-GlcNAc modification	927:960	The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro.
29530619	4	28	theme	voltage-gated	503:515	arg1	Nav1.5					533:538	Nav1.5	533:538	Nav1.5	533:538	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	4	28	theme	voltage-gated	503:515	arg1	channel					524:530	the cardiac voltage-gated sodium channel	491:530	the cardiac voltage-gated sodium channel (Nav1.5)	491:539	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	10	29	theme	function	1744:1751	arg1	prolongation					1780:1791	prolongation	1780:1791	prolongation of the PR/QT interval	1780:1813	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	29	theme	function	1744:1751	arg1	distribution					1712:1723	distribution	1712:1723	distribution	1712:1723	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	29	theme	function	1744:1751	arg1	expression					1697:1706	abnormal expression	1688:1706	abnormal expression	1688:1706	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	29	theme	function	1744:1751	arg1	loss					1736:1739	loss	1736:1739	loss of function of the sodium channel	1736:1773	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	0	30	theme	cardiac	19:25	arg1	Nav1.5					27:32	cardiac Nav1.5	19:32	cardiac Nav1.5	19:32	O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts.
29530619	9	31	theme	high-glucose	1417:1428	arg1	treatment					1430:1438	high-glucose treatment	1417:1438	high-glucose treatment	1417:1438	Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.
29530619	6	32	theme	diabetic	850:857	arg1	rats					859:862	STZ-induced 3-month diabetic rats	830:862	STZ-induced 3-month diabetic rats	830:862	STZ-induced 3-month diabetic rats displayed increased susceptibility to ventricular arrhythmias.
29530619	1	33	theme	Cardiovascular	111:124	arg1	complications					126:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	1	33	theme	Cardiovascular	111:124	arg1	causes					150:155	major causes	144:155	major causes of mortality and morbidity in diabetic patients	144:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	5	34	dep	METHODS	649:655	arg1	treated					727:733	treated	727:733	were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes	722:827	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	10	35	theme	Nav1.5	1588:1593	arg1	expression					1595:1604	Nav1.5 expression	1588:1604	Nav1.5 expression	1588:1604	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	36	theme	channel	1767:1773	arg1	function					1744:1751	function	1744:1751	function of the sodium channel	1744:1773	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	6	37	theme	STZ-induced	830:840	arg1	rats					859:862	STZ-induced 3-month diabetic rats	830:862	STZ-induced 3-month diabetic rats	830:862	STZ-induced 3-month diabetic rats displayed increased susceptibility to ventricular arrhythmias.
29530619	3	38	theme	cellular	423:430	arg1	processes					432:440	diverse cellular processes	415:440	diverse cellular processes	415:440	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	8	39	dep	Nav1.5	1249:1254	arg1	Nedd4-2/SAP-97					1284:1297	Nedd4-2/SAP-97	1284:1297	Nedd4-2/SAP-97	1284:1297	In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97.
29530619	10	40	theme	PR/QT	1800:1804	arg1	interval					1806:1813	the PR/QT interval	1796:1813	the PR/QT interval	1796:1813	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	11	41	theme	O-GlcNAc	1826:1833	arg1	modification					1835:1846	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	41	theme	O-GlcNAc	1826:1833	arg1	factor					1926:1931	an underlying contributing factor	1899:1931	an underlying contributing factor for the development of the arrhythmogenesis in DH	1899:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	41	theme	O-GlcNAc	1826:1833	arg1	event					1879:1883	a novel signaling event	1861:1883	a novel signaling event	1861:1883	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	4	42	theme	essential	607:615	arg1	role					617:620	an essential role	604:620	an essential role	604:620	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	10	43	dep	CONCLUSION	1500:1509	arg1	suggested					1520:1528	suggested	1520:1528	suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval	1520:1813	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	6	44	theme	ventricular	902:912	arg1	arrhythmias					914:924	ventricular arrhythmias	902:924	ventricular arrhythmias	902:924	STZ-induced 3-month diabetic rats displayed increased susceptibility to ventricular arrhythmias.
29530619	8	45	theme	Nav1.5	1198:1203	arg1	levels					1205:1210	the O-GlcNAc-modified Nav1.5 levels	1176:1210	the O-GlcNAc-modified Nav1.5 levels	1176:1210	In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97.
29530619	4	46	link	O-linked	557:564	arg1	O-GlcNAc					581:588	O-GlcNAc	581:588	O-GlcNAc	581:588	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	4	46	link	O-linked	557:564	arg1	GlcNAcylation					566:578	O-linked GlcNAcylation	557:578	O-linked GlcNAcylation (O-GlcNAc)	557:589	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	10	47	dep	expression	1697:1706	arg1	the					1684:1686	the	1684:1686	the	1684:1686	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	5	48	theme	rat	807:809	arg1	model					811:815	a rat model	805:815	a rat model of diabetes	805:827	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	5	49	dep	streptozotocin	762:775	arg1	80 mg/kg					783:790	80 mg/kg	783:790	80 mg/kg	783:790	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	5	49	dep	streptozotocin	762:775	arg1	STZ					778:780	STZ	778:780	STZ	778:780	METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes.
29530619	2	50	theme	heart	260:264	arg1	progression					236:246	the progression	232:246	the progression of diabetic heart (DH) to ventricular arrhythmias	232:296	The mechanisms underlying the progression of diabetic heart (DH) to ventricular arrhythmias are unclear.
29530619	10	51	theme	Nav1.5	1728:1733	arg1	prolongation					1780:1791	prolongation	1780:1791	prolongation of the PR/QT interval	1780:1813	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	51	theme	Nav1.5	1728:1733	arg1	distribution					1712:1723	distribution	1712:1723	distribution	1712:1723	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	51	theme	Nav1.5	1728:1733	arg1	expression					1697:1706	abnormal expression	1688:1706	abnormal expression	1688:1706	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	10	51	theme	Nav1.5	1728:1733	arg1	loss					1736:1739	loss	1736:1739	loss of function of the sodium channel	1736:1773	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	9	52	theme	patch-clamp	1313:1323	arg1	measurements					1325:1336	patch-clamp measurements	1313:1336	patch-clamp measurements in HEK-293 T cells	1313:1355	Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.
29530619	11	53	theme	underlying	1902:1911	arg1	modification					1835:1846	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	53	theme	underlying	1902:1911	arg1	event					1879:1883	a novel signaling event	1861:1883	a novel signaling event	1861:1883	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	53	theme	underlying	1902:1911	arg1	factor					1926:1931	an underlying contributing factor	1899:1931	an underlying contributing factor for the development of the arrhythmogenesis in DH	1899:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	7	54	theme	Nav1.5	1022:1027	arg1	expression					1029:1038	both total and cytoplasmic Nav1.5 expression	995:1038	both total and cytoplasmic Nav1.5 expression	995:1038	The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro.
29530619	1	55	theme	major	144:148	arg1	complications					126:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	1	55	theme	major	144:148	arg1	causes					150:155	major causes	144:155	major causes of mortality and morbidity in diabetic patients	144:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	3	56	theme	O-linked	311:318	arg1	modification					380:391	a reversible post-translational modification	348:391	a reversible post-translational modification for the regulation of diverse cellular processes	348:440	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	3	56	theme	O-linked	311:318	arg1	O-GlcNAc					335:342	O-GlcNAc	335:342	O-GlcNAc	335:342	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	3	56	theme	O-linked	311:318	arg1	GlcNAcylation					320:332	O-linked GlcNAcylation	311:332	O-linked GlcNAcylation (O-GlcNAc)	311:343	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	4	57	theme	study	463:467	arg1	purpose					447:453	The purpose	443:453	The purpose of this study	443:467	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	0	58	theme	arrhythmias	68:78	arg1	development					53:63	the development	49:63	the development of arrhythmias in diabetic hearts	49:97	O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts.
29530619	0	59	theme	diabetic	83:90	arg1	hearts					92:97	diabetic hearts	83:97	diabetic hearts	83:97	O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts.
29530619	0	60	from	development	53:63	arg1	hearts					92:97	diabetic hearts	83:97	diabetic hearts	83:97	O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts.
29530619	7	61	from	decreases	982:990	arg1	expression					1029:1038	both total and cytoplasmic Nav1.5 expression	995:1038	both total and cytoplasmic Nav1.5 expression	995:1038	The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro.
29530619	9	62	theme	current	1376:1382	arg1	densities					1384:1392	Nav1.5 current densities	1369:1392	Nav1.5 current densities	1369:1392	Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.
29530619	1	63	from	morbidity	174:182	arg1	patients					196:203	diabetic patients	187:203	diabetic patients	187:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	4	64	theme	cardiac	495:501	arg1	Nav1.5					533:538	Nav1.5	533:538	Nav1.5	533:538	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	4	64	theme	cardiac	495:501	arg1	channel					524:530	the cardiac voltage-gated sodium channel	491:530	the cardiac voltage-gated sodium channel (Nav1.5)	491:539	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	11	65	theme	novel	1863:1867	arg1	modification					1835:1846	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	65	theme	novel	1863:1867	arg1	factor					1926:1931	an underlying contributing factor	1899:1931	an underlying contributing factor for the development of the arrhythmogenesis in DH	1899:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	65	theme	novel	1863:1867	arg1	event					1879:1883	a novel signaling event	1861:1883	a novel signaling event	1861:1883	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	1	66	from	mortality	160:168	arg1	patients					196:203	diabetic patients	187:203	diabetic patients	187:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	3	67	theme	post-translational	361:378	arg1	GlcNAcylation					320:332	O-linked GlcNAcylation	311:332	O-linked GlcNAcylation (O-GlcNAc)	311:343	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	3	67	theme	post-translational	361:378	arg1	modification					380:391	a reversible post-translational modification	348:391	a reversible post-translational modification for the regulation of diverse cellular processes	348:440	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	4	68	theme	sodium	517:522	arg1	Nav1.5					533:538	Nav1.5	533:538	Nav1.5	533:538	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	4	68	theme	sodium	517:522	arg1	channel					524:530	the cardiac voltage-gated sodium channel	491:530	the cardiac voltage-gated sodium channel (Nav1.5)	491:539	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	10	69	theme	O-GlcNAc	1563:1570	arg1	modification					1572:1583	the O-GlcNAc modification	1559:1583	the O-GlcNAc modification of Nav1.5 expression	1559:1604	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	1	70	from	causes	150:155	arg1	patients					196:203	diabetic patients	187:203	diabetic patients	187:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	3	71	theme	diverse	415:421	arg1	processes					432:440	diverse cellular processes	415:440	diverse cellular processes	415:440	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	11	72	from	development	1941:1951	arg1	DH					1980:1981	DH	1980:1981	DH	1980:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	0	73	theme	Nav1.5	27:32	arg1	O-GlcNAcylation					0:14	O-GlcNAcylation	0:14	O-GlcNAcylation of cardiac Nav1.5	0:32	O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts.
29530619	8	74	theme	co-immunoprecipitation	1080:1101	arg1	assays					1122:1127	both co-immunoprecipitation and immunostaining assays	1075:1127	both co-immunoprecipitation and immunostaining assays	1075:1127	In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97.
29530619	7	75	theme	elevated	931:938	arg1	modification					949:960	The elevated O-GlcNAc modification	927:960	The elevated O-GlcNAc modification	927:960	The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro.
29530619	1	76	theme	BACKGROUND	100:109	arg1	complications					126:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications	100:138	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	1	76	theme	BACKGROUND	100:109	arg1	causes					150:155	major causes	144:155	major causes of mortality and morbidity in diabetic patients	144:203	BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients.
29530619	10	77	theme	expression	1595:1604	arg1	modification					1572:1583	the O-GlcNAc modification	1559:1583	the O-GlcNAc modification of Nav1.5 expression	1559:1604	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	8	78	theme	immunostaining	1107:1120	arg1	assays					1122:1127	both co-immunoprecipitation and immunostaining assays	1075:1127	both co-immunoprecipitation and immunostaining assays	1075:1127	In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97.
29530619	6	79	theme	3-month	842:848	arg1	rats					859:862	STZ-induced 3-month diabetic rats	830:862	STZ-induced 3-month diabetic rats	830:862	STZ-induced 3-month diabetic rats displayed increased susceptibility to ventricular arrhythmias.
29530619	10	80	theme	sodium	1760:1765	arg1	channel					1767:1773	the sodium channel	1756:1773	the sodium channel	1756:1773	CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval.
29530619	3	81	theme	processes	432:440	arg1	regulation					401:410	the regulation	397:410	the regulation of diverse cellular processes	397:440	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	4	82	theme	O-linked	557:564	arg1	O-GlcNAc					581:588	O-GlcNAc	581:588	O-GlcNAc	581:588	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	4	82	theme	O-linked	557:564	arg1	GlcNAcylation					566:578	O-linked GlcNAcylation	557:578	O-linked GlcNAcylation (O-GlcNAc)	557:589	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	11	83	theme	Excessive	1816:1824	arg1	modification					1835:1846	Excessive O-GlcNAc modification	1816:1846	Excessive O-GlcNAc modification of Nav1.5	1816:1856	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	83	theme	Excessive	1816:1824	arg1	factor					1926:1931	an underlying contributing factor	1899:1931	an underlying contributing factor for the development of the arrhythmogenesis in DH	1899:1981	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	11	83	theme	Excessive	1816:1824	arg1	event					1879:1883	a novel signaling event	1861:1883	a novel signaling event	1861:1883	Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.
29530619	3	84	link	O-linked	311:318	arg1	modification					380:391	a reversible post-translational modification	348:391	a reversible post-translational modification for the regulation of diverse cellular processes	348:440	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	3	84	link	O-linked	311:318	arg1	O-GlcNAc					335:342	O-GlcNAc	335:342	O-GlcNAc	335:342	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	3	84	link	O-linked	311:318	arg1	GlcNAcylation					320:332	O-linked GlcNAcylation	311:332	O-linked GlcNAcylation (O-GlcNAc)	311:343	O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes.
29530619	9	85	theme	sodium	1449:1454	arg1	currents					1456:1463	the sodium currents	1445:1463	the sodium currents	1445:1463	Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.
29530619	4	86	theme	DH-induced	625:634	arg1	arrhythmias					636:646	DH-induced arrhythmias	625:646	DH-induced arrhythmias	625:646	The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias.
29530619	9	87	theme	O-GlcNAc	1479:1486	arg1	inhibition					1488:1497	O-GlcNAc inhibition	1479:1497	O-GlcNAc inhibition	1479:1497	Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition.
30966639	0	0	theme	Carboxymethyl	90:102	arg1	Cellulose					104:112	Carboxymethyl Cellulose	90:112	Carboxymethyl Cellulose	90:112	Preparation and Characterization of Superabsorbent Polymers Based on Starch Aldehydes and Carboxymethyl Cellulose.
30966639	8	1	theme	ester	1071:1075	arg1	bridges					1077:1083	the ester bridges	1067:1083	the ester bridges from citric acid	1067:1100	However, the ester bridges from citric acid interfered with the water penetration.
30966639	10	2	theme	SAPs	1350:1353	arg1	morphology					1332:1341	morphology	1332:1341	morphology	1332:1341	The relationship between swelling behavior and morphology of the SAPs was analyzed by FE-SEM images.
30966639	10	2	theme	SAPs	1350:1353	arg1	behavior					1319:1326	swelling behavior	1310:1326	swelling behavior	1310:1326	The relationship between swelling behavior and morphology of the SAPs was analyzed by FE-SEM images.
30966639	7	3	theme	starch	966:971	arg1	aldehydes					973:981	starch aldehydes	966:981	starch aldehydes	966:981	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	5	4	theme	periodate	646:654	arg1	oxidation					656:664	periodate oxidation	646:664	periodate oxidation	646:664	Starch aldehydes were prepared by periodate oxidation, which forms aldehyde groups by taking the places of C⁻OH groups at C-2 and C-3.
30966639	9	5	dep	Schott	1240:1245	arg1	kinetics					1269:1276	pseudo second order kinetics	1249:1276	the Schott's pseudo second order kinetics model	1236:1282	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	11	6	theme	polysaccharide-based	1401:1420	arg1	SAPs					1422:1425	polysaccharide-based SAPs	1401:1425	polysaccharide-based SAPs	1401:1425	In conclusion, polysaccharide-based SAPs were well prepared and the highest equilibrium swelling ratio was 87.0 g/g.
30966639	9	7	theme	SAPs	1183:1186	arg1	behavior					1167:1174	the swelling behavior	1154:1174	the swelling behavior of the SAPs	1154:1186	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	6	8	from	morphology	863:872	arg1	spectra					819:825	FT-IR spectra	813:825	FT-IR spectra	813:825	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	6	8	from	morphology	863:872	arg1	images					884:889	FE-SEM images	877:889	FE-SEM images	877:889	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	11	9	theme	swelling	1474:1481	arg1	ratio					1483:1487	the highest equilibrium swelling ratio	1450:1487	the highest equilibrium swelling ratio	1450:1487	In conclusion, polysaccharide-based SAPs were well prepared and the highest equilibrium swelling ratio was 87.0 g/g.
30966639	11	9	theme	swelling	1474:1481	arg1	g/g					1498:1500	87.0 g/g	1493:1500	87.0 g/g	1493:1500	In conclusion, polysaccharide-based SAPs were well prepared and the highest equilibrium swelling ratio was 87.0 g/g.
30966639	11	10	theme	highest	1454:1460	arg1	ratio					1483:1487	the highest equilibrium swelling ratio	1450:1487	the highest equilibrium swelling ratio	1450:1487	In conclusion, polysaccharide-based SAPs were well prepared and the highest equilibrium swelling ratio was 87.0 g/g.
30966639	11	10	theme	highest	1454:1460	arg1	g/g					1498:1500	87.0 g/g	1493:1500	87.0 g/g	1493:1500	In conclusion, polysaccharide-based SAPs were well prepared and the highest equilibrium swelling ratio was 87.0 g/g.
30966639	3	11	theme	polysaccharide-based	352:371	arg1	SAPs					373:376	polysaccharide-based SAPs	352:376	polysaccharide-based SAPs using carboxymethyl cellulose as a major component	352:427	Therefore, in this study, polysaccharide-based SAPs using carboxymethyl cellulose as a major component were prepared.
30966639	4	12	theme	environment-friendly	504:523	arg1	properties					555:564	their environment-friendly, non-toxic, and biodegradable properties	498:564	their environment-friendly, non-toxic, and biodegradable properties	498:564	Starch aldehydes and citric acid were selected due to their environment-friendly, non-toxic, and biodegradable properties compared to conventional crosslinking agents.
30966639	5	13	theme	Starch	612:617	arg1	aldehydes					619:627	Starch aldehydes	612:627	Starch aldehydes	612:627	Starch aldehydes were prepared by periodate oxidation, which forms aldehyde groups by taking the places of C⁻OH groups at C-2 and C-3.
30966639	5	14	theme	aldehyde	679:686	arg1	groups					688:693	aldehyde groups	679:693	aldehyde groups	679:693	Starch aldehydes were prepared by periodate oxidation, which forms aldehyde groups by taking the places of C⁻OH groups at C-2 and C-3.
30966639	6	15	theme	FT-IR	813:817	arg1	spectra					819:825	FT-IR spectra	813:825	FT-IR spectra	813:825	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	6	16	from	quantitation	841:852	arg1	spectra					819:825	FT-IR spectra	813:825	FT-IR spectra	813:825	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	6	16	from	quantitation	841:852	arg1	images					884:889	FE-SEM images	877:889	FE-SEM images	877:889	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	4	17	theme	crosslinking	591:602	arg1	agents					604:609	conventional crosslinking agents	578:609	conventional crosslinking agents	578:609	Starch aldehydes and citric acid were selected due to their environment-friendly, non-toxic, and biodegradable properties compared to conventional crosslinking agents.
30966639	7	18	theme	acetal	946:951	arg1	bridges					953:959	the acetal bridges	942:959	the acetal bridges from starch aldehydes	942:981	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	9	19	theme	Schott	1240:1245	arg1	model					1278:1282	the Schott's pseudo second order kinetics model	1236:1282	the Schott's pseudo second order kinetics model	1236:1282	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	10	20	theme	swelling	1310:1317	arg1	behavior					1319:1326	swelling behavior	1310:1326	swelling behavior	1310:1326	The relationship between swelling behavior and morphology of the SAPs was analyzed by FE-SEM images.
30966639	3	21	theme	carboxymethyl	384:396	arg1	component					419:427	a major component	411:427	a major component	411:427	Therefore, in this study, polysaccharide-based SAPs using carboxymethyl cellulose as a major component were prepared.
30966639	3	21	theme	carboxymethyl	384:396	arg1	cellulose					398:406	carboxymethyl cellulose	384:406	carboxymethyl cellulose	384:406	Therefore, in this study, polysaccharide-based SAPs using carboxymethyl cellulose as a major component were prepared.
30966639	4	22	theme	conventional	578:589	arg1	agents					604:609	conventional crosslinking agents	578:609	conventional crosslinking agents	578:609	Starch aldehydes and citric acid were selected due to their environment-friendly, non-toxic, and biodegradable properties compared to conventional crosslinking agents.
30966639	9	23	theme	Fickian	1208:1214	arg1	model					1226:1230	the Fickian diffusion model	1204:1230	the Fickian diffusion model	1204:1230	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	1	24	theme	Superabsorbent	115:128	arg1	polymers					174:181	crosslinked hydrophilic polymers	150:181	crosslinked hydrophilic polymers that are capable of absorbing large amounts of water	150:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	1	24	theme	Superabsorbent	115:128	arg1	SAPs					140:143	SAPs	140:143	SAPs	140:143	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	1	24	theme	Superabsorbent	115:128	arg1	polymers					130:137	Superabsorbent polymers	115:137	Superabsorbent polymers (SAPs)	115:144	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	11	25	theme	equilibrium	1462:1472	arg1	ratio					1483:1487	the highest equilibrium swelling ratio	1450:1487	the highest equilibrium swelling ratio	1450:1487	In conclusion, polysaccharide-based SAPs were well prepared and the highest equilibrium swelling ratio was 87.0 g/g.
30966639	11	25	theme	equilibrium	1462:1472	arg1	g/g					1498:1500	87.0 g/g	1493:1500	87.0 g/g	1493:1500	In conclusion, polysaccharide-based SAPs were well prepared and the highest equilibrium swelling ratio was 87.0 g/g.
30966639	1	26	theme	large	213:217	arg1	amounts					219:225	large amounts	213:225	large amounts of water	213:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	1	26	theme	large	213:217	arg1	water					230:234	water	230:234	water	230:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	7	27	theme	water	1008:1012	arg1	water					1008:1012	water	1008:1012	water entering the network structure of the SAPs	1008:1055	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	7	27	theme	water	1008:1012	arg1	amount					998:1003	a large amount	990:1003	a large amount of water entering the network structure of the SAPs	990:1055	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	9	28	theme	diffusion	1216:1224	arg1	model					1226:1230	the Fickian diffusion model	1204:1230	the Fickian diffusion model	1204:1230	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	7	29	from	aldehydes	973:981	arg1	bridges					953:959	the acetal bridges	942:959	the acetal bridges from starch aldehydes	942:981	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	6	30	from	change	803:808	arg1	spectra					819:825	FT-IR spectra	813:825	FT-IR spectra	813:825	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	6	30	from	change	803:808	arg1	images					884:889	FE-SEM images	877:889	FE-SEM images	877:889	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	0	31	theme	Polymers	51:58	arg1	Characterization					16:31	Characterization	16:31	Characterization	16:31	Preparation and Characterization of Superabsorbent Polymers Based on Starch Aldehydes and Carboxymethyl Cellulose.
30966639	0	31	theme	Polymers	51:58	arg1	Preparation					0:10	Preparation	0:10	Preparation	0:10	Preparation and Characterization of Superabsorbent Polymers Based on Starch Aldehydes and Carboxymethyl Cellulose.
30966639	1	32	link	crosslinked	150:160	arg1	polymers					174:181	crosslinked hydrophilic polymers	150:181	crosslinked hydrophilic polymers that are capable of absorbing large amounts of water	150:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	1	32	link	crosslinked	150:160	arg1	polymers					130:137	Superabsorbent polymers	115:137	Superabsorbent polymers (SAPs)	115:144	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	4	33	theme	citric	465:470	arg1	acid					472:475	citric acid	465:475	citric acid	465:475	Starch aldehydes and citric acid were selected due to their environment-friendly, non-toxic, and biodegradable properties compared to conventional crosslinking agents.
30966639	0	34	theme	Superabsorbent	36:49	arg1	Polymers					51:58	Superabsorbent Polymers	36:58	Superabsorbent Polymers	36:58	Preparation and Characterization of Superabsorbent Polymers Based on Starch Aldehydes and Carboxymethyl Cellulose.
30966639	8	35	theme	citric	1090:1095	arg1	acid					1097:1100	citric acid	1090:1100	citric acid	1090:1100	However, the ester bridges from citric acid interfered with the water penetration.
30966639	6	36	theme	FE-SEM	877:882	arg1	images					884:889	FE-SEM images	877:889	FE-SEM images	877:889	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	7	37	theme	network	1027:1033	arg1	structure					1035:1043	the network structure	1023:1043	the network structure of the SAPs	1023:1055	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	1	38	theme	water	230:234	arg1	amounts					219:225	large amounts	213:225	large amounts of water	213:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	1	38	theme	water	230:234	arg1	water					230:234	water	230:234	water	230:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	3	39	theme	major	413:417	arg1	component					419:427	a major component	411:427	a major component	411:427	Therefore, in this study, polysaccharide-based SAPs using carboxymethyl cellulose as a major component were prepared.
30966639	3	39	theme	major	413:417	arg1	cellulose					398:406	carboxymethyl cellulose	384:406	carboxymethyl cellulose	384:406	Therefore, in this study, polysaccharide-based SAPs using carboxymethyl cellulose as a major component were prepared.
30966639	4	40	theme	biodegradable	541:553	arg1	properties					555:564	their environment-friendly, non-toxic, and biodegradable properties	498:564	their environment-friendly, non-toxic, and biodegradable properties	498:564	Starch aldehydes and citric acid were selected due to their environment-friendly, non-toxic, and biodegradable properties compared to conventional crosslinking agents.
30966639	7	41	theme	SAPs	1052:1055	arg1	structure					1035:1043	the network structure	1023:1043	the network structure of the SAPs	1023:1055	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	2	42	theme	Commercial	237:246	arg1	SAPs					248:251	Commercial SAPs	237:251	Commercial SAPs	237:251	Commercial SAPs are mostly produced with acrylic acid that cannot be easily biodegraded.
30966639	8	43	theme	water	1122:1126	arg1	penetration					1128:1138	the water penetration	1118:1138	the water penetration	1118:1138	However, the ester bridges from citric acid interfered with the water penetration.
30966639	9	44	theme	order	1263:1267	arg1	kinetics					1269:1276	pseudo second order kinetics	1249:1276	the Schott's pseudo second order kinetics model	1236:1282	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	5	45	theme	C⁻OH	719:722	arg1	groups					724:729	C⁻OH groups	719:729	C⁻OH groups	719:729	Starch aldehydes were prepared by periodate oxidation, which forms aldehyde groups by taking the places of C⁻OH groups at C-2 and C-3.
30966639	4	46	theme	Starch	444:449	arg1	aldehydes					451:459	Starch aldehydes	444:459	Starch aldehydes	444:459	Starch aldehydes and citric acid were selected due to their environment-friendly, non-toxic, and biodegradable properties compared to conventional crosslinking agents.
30966639	5	47	theme	groups	724:729	arg1	places					709:714	the places	705:714	the places of C⁻OH groups	705:729	Starch aldehydes were prepared by periodate oxidation, which forms aldehyde groups by taking the places of C⁻OH groups at C-2 and C-3.
30966639	2	48	theme	acrylic	278:284	arg1	acid					286:289	acrylic acid	278:289	acrylic acid that cannot be easily biodegraded	278:323	Commercial SAPs are mostly produced with acrylic acid that cannot be easily biodegraded.
30966639	6	49	theme	aldehyde	832:839	arg1	quantitation					841:852	the aldehyde quantitation	828:852	the aldehyde quantitation	828:852	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	10	50	theme	FE-SEM	1371:1376	arg1	images					1378:1383	FE-SEM images	1371:1383	FE-SEM images	1371:1383	The relationship between swelling behavior and morphology of the SAPs was analyzed by FE-SEM images.
30966639	9	51	theme	swelling	1158:1165	arg1	behavior					1167:1174	the swelling behavior	1154:1174	the swelling behavior of the SAPs	1154:1186	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	8	52	from	acid	1097:1100	arg1	bridges					1077:1083	the ester bridges	1067:1083	the ester bridges from citric acid	1067:1100	However, the ester bridges from citric acid interfered with the water penetration.
30966639	9	53	theme	pseudo	1249:1254	arg1	kinetics					1269:1276	pseudo second order kinetics	1249:1276	the Schott's pseudo second order kinetics model	1236:1282	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	7	54	theme	polysaccharide-based	915:934	arg1	SAPs					936:939	polysaccharide-based SAPs	915:939	polysaccharide-based SAPs	915:939	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	9	55	theme	second	1256:1261	arg1	kinetics					1269:1276	pseudo second order kinetics	1249:1276	the Schott's pseudo second order kinetics model	1236:1282	In addition, the swelling behavior of the SAPs was analyzed by the Fickian diffusion model and the Schott's pseudo second order kinetics model.
30966639	6	56	theme	starch	760:765	arg1	aldehydes					767:775	starch aldehydes	760:775	starch aldehydes	760:775	Furthermore, starch aldehydes were analyzed through the change in FT-IR spectra, the aldehyde quantitation, and the morphology in FE-SEM images.
30966639	1	57	theme	crosslinked	150:160	arg1	polymers					174:181	crosslinked hydrophilic polymers	150:181	crosslinked hydrophilic polymers that are capable of absorbing large amounts of water	150:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	1	57	theme	crosslinked	150:160	arg1	polymers					130:137	Superabsorbent polymers	115:137	Superabsorbent polymers (SAPs)	115:144	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	7	58	theme	SAPs	936:939	arg1	crosslinking					899:910	the crosslinking	895:910	the crosslinking of polysaccharide-based SAPs	895:939	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	0	59	theme	Starch	69:74	arg1	Aldehydes					76:84	Starch Aldehydes	69:84	Starch Aldehydes	69:84	Preparation and Characterization of Superabsorbent Polymers Based on Starch Aldehydes and Carboxymethyl Cellulose.
30966639	4	60	theme	non-toxic	526:534	arg1	properties					555:564	their environment-friendly, non-toxic, and biodegradable properties	498:564	their environment-friendly, non-toxic, and biodegradable properties	498:564	Starch aldehydes and citric acid were selected due to their environment-friendly, non-toxic, and biodegradable properties compared to conventional crosslinking agents.
30966639	7	61	theme	large	992:996	arg1	water					1008:1012	water	1008:1012	water entering the network structure of the SAPs	1008:1055	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	7	61	theme	large	992:996	arg1	amount					998:1003	a large amount	990:1003	a large amount of water entering the network structure of the SAPs	990:1055	In the crosslinking of polysaccharide-based SAPs, the acetal bridges from starch aldehydes led to a large amount of water entering the network structure of the SAPs.
30966639	1	62	theme	hydrophilic	162:172	arg1	polymers					174:181	crosslinked hydrophilic polymers	150:181	crosslinked hydrophilic polymers that are capable of absorbing large amounts of water	150:234	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
30966639	1	62	theme	hydrophilic	162:172	arg1	polymers					130:137	Superabsorbent polymers	115:137	Superabsorbent polymers (SAPs)	115:144	Superabsorbent polymers (SAPs) are crosslinked hydrophilic polymers that are capable of absorbing large amounts of water.
31887499	2	0	with	soils	356:360	arg1	presence					417:424	the presence	413:424	the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	413:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	2	1	theme	River	328:332	arg1	soils					356:360	three Mississippi River deltaic plain wetland soils	310:360	three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	310:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	8	2	from	differences	1393:1403	arg1	DOM					1413:1415	soil DOM	1408:1415	soil DOM	1408:1415	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	8	2	from	differences	1393:1403	arg1	community					1431:1439	microbial community	1421:1439	microbial community	1421:1439	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	4	3	theme	forest	814:819	arg1	soil					821:824	swamp forest soil	808:824	swamp forest soil	808:824	Addition of NO3- promoted CO2 production in swamp forest soil, but inhibited CO2 emission from marsh soils.
31887499	2	4	from	production	296:305	arg1	soils					356:360	three Mississippi River deltaic plain wetland soils	310:360	three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	310:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	5	5	contain	contained	920:928	arg2	polysaccharides					935:949	more polysaccharides	930:949	more polysaccharides	930:949	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	5	5	contain	contained	920:928	arg1	soil					915:918	swamp soil	909:918	swamp soil	909:918	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	8	6	theme	NO3-	1542:1545	arg1	loading					1547:1553	NO3- loading	1542:1553	NO3- loading	1542:1553	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	4	7	theme	NO3-	776:779	arg1	Addition					764:771	Addition	764:771	Addition of NO3-	764:779	Addition of NO3- promoted CO2 production in swamp forest soil, but inhibited CO2 emission from marsh soils.
31887499	4	8	theme	CO2	790:792	arg1	production					794:803	CO2 production	790:803	CO2 production	790:803	Addition of NO3- promoted CO2 production in swamp forest soil, but inhibited CO2 emission from marsh soils.
31887499	6	9	theme	higher	1069:1074	arg1	%					1067:1067	66%	1065:1067	66% higher than freshwater and saline marsh soils	1065:1113	Total PLFAs of forest swamp soil were 34% and 66% higher than freshwater and saline marsh soils, respectively.
31887499	3	10	theme	lipid	693:697	arg1	PLFA					711:714	PLFA	711:714	PLFA	711:714	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	3	10	theme	lipid	693:697	arg1	acid					705:708	phosphorus lipid fatty acid	682:708	phosphorus lipid fatty acid (PLFA) method	682:722	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	7	11	with	gradient	1208:1215	arg1	swamp					1233:1237	the forest swamp	1222:1237	the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1222:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	1	12	theme	nitrate	176:182	arg1	effect					166:171	the effect	162:171	the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions	162:274	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	6	13	dep	freshwater	1081:1090	arg1	soils					1109:1113	marsh soils	1103:1113	marsh soils	1103:1113	Total PLFAs of forest swamp soil were 34% and 66% higher than freshwater and saline marsh soils, respectively.
31887499	5	14	theme	phenolic	999:1006	arg1	compounds					1008:1016	phenolic compounds	999:1016	phenolic compounds	999:1016	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	4	15	theme	marsh	859:863	arg1	soils					865:869	marsh soils	859:869	marsh soils	859:869	Addition of NO3- promoted CO2 production in swamp forest soil, but inhibited CO2 emission from marsh soils.
31887499	7	16	theme	lower	1297:1301	arg1	SO42-					1312:1316	SO42-	1312:1316	SO42-	1312:1316	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	7	16	theme	lower	1297:1301	arg1	sulfate					1303:1309	lower sulfate	1297:1309	lower sulfate (SO42-) reducers	1297:1326	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	1	17	from	soils	228:232	arg1	emissions					205:213	carbon gas emissions	194:213	carbon gas emissions from wetland soils that contradict thermodynamic predictions	194:274	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	3	18	theme	dissolved	540:548	arg1	matter					558:563	dissolved organic matter	540:563	dissolved organic matter (DOM) of these soils	540:584	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	3	18	theme	dissolved	540:548	arg1	DOM					566:568	DOM	566:568	DOM	566:568	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	9	19	theme	nitrate	1622:1628	arg1	fate					1614:1617	the fate	1610:1617	the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management	1610:1725	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	0	20	from	levels	64:69	arg1	Gulf					74:77	Gulf	74:77	Gulf	74:77	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	7	21	theme	reducers	1284:1291	arg1	proportion					1255:1264	a higher proportion	1246:1264	a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1246:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	9	22	theme	Louisiana	1639:1647	arg1	wetlands					1657:1664	Louisiana coastal wetlands	1639:1664	Louisiana coastal wetlands from river diversions and other sources	1639:1704	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	3	23	theme	acid	705:708	arg1	method					717:722	phosphorus lipid fatty acid (PLFA) method	682:722	phosphorus lipid fatty acid (PLFA) method	682:722	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	5	24	theme	high	981:984	arg1	abundance					986:994	high abundance	981:994	high abundance of phenolic compounds	981:1016	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	2	25	theme	anaerobic	494:502	arg1	microcosm					504:512	an anaerobic microcosm	491:512	an anaerobic microcosm	491:512	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	3	26	theme	matter	558:563	arg1	composition					525:535	Molecular composition	515:535	Molecular composition of dissolved organic matter (DOM) of these soils	515:584	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	9	27	theme	river	1671:1675	arg1	diversions					1677:1686	river diversions	1671:1686	river diversions	1671:1686	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	8	28	theme	soil	1408:1411	arg1	DOM					1413:1415	soil DOM	1408:1415	soil DOM	1408:1415	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	3	29	theme	underlying	741:750	arg1	mechanisms					752:761	the underlying mechanisms	737:761	the underlying mechanisms	737:761	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	0	30	theme	Mexico	82:87	arg1	wetlands					97:104	Mexico coastal wetlands	82:104	Mexico coastal wetlands: Phenomena and relationships	82:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	0	31	dep	wetlands	97:104	arg1	relationships					121:133	relationships	121:133	relationships	121:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	0	31	dep	wetlands	97:104	arg1	Phenomena					107:115	Phenomena	107:115	Phenomena	107:115	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	1	32	theme	thermodynamic	250:262	arg1	predictions					264:274	thermodynamic predictions	250:274	thermodynamic predictions	250:274	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	2	33	theme	saline	392:397	arg1	marshes					399:405	saline marshes	392:405	saline marshes	392:405	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	2	33	theme	saline	392:397	arg1	swamp					370:374	forest swamp	363:374	forest swamp	363:374	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	0	34	theme	CO2	20:22	arg1	production					24:33	anaerobic CO2 production	10:33	anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships	10:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	9	35	from	sources	1698:1704	arg1	wetlands					1657:1664	Louisiana coastal wetlands	1639:1664	Louisiana coastal wetlands from river diversions and other sources	1639:1704	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	9	35	from	sources	1698:1704	arg1	management					1716:1725	their management	1710:1725	their management	1710:1725	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	2	36	theme	NO3-	439:442	arg1	levels					444:449	different NO3- levels	429:449	different NO3- levels (0.2, 2.0, and 3.2 mM)	429:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	8	37	theme	contrasting	1452:1462	arg1	response					1464:1471	the contrasting response	1448:1471	the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading	1448:1553	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	3	38	theme	soils	580:584	arg1	matter					558:563	dissolved organic matter	540:563	dissolved organic matter (DOM) of these soils	540:584	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	3	38	theme	soils	580:584	arg1	DOM					566:568	DOM	566:568	DOM	566:568	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	2	39	theme	Mississippi	316:326	arg1	soils					356:360	three Mississippi River deltaic plain wetland soils	310:360	three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	310:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	0	40	theme	elevated	47:54	arg1	levels					64:69	elevated nitrate levels	47:69	elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships	47:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	2	41	dep	levels	444:449	arg1	2.0					457:459	2.0	457:459	2.0	457:459	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	2	41	dep	levels	444:449	arg1	3.2 mM					466:471	3.2 mM	466:471	3.2 mM	466:471	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	8	42	theme	CO2	1481:1483	arg1	respiration					1485:1495	soil CO2 respiration	1476:1495	soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading	1476:1553	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	1	43	theme	carbon	194:199	arg1	emissions					205:213	carbon gas emissions	194:213	carbon gas emissions from wetland soils that contradict thermodynamic predictions	194:274	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	5	44	theme	more	930:933	arg1	polysaccharides					935:949	more polysaccharides	930:949	more polysaccharides	930:949	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	6	45	theme	soil	1047:1050	arg1	PLFAs					1025:1029	Total PLFAs	1019:1029	Total PLFAs of forest swamp soil	1019:1050	Total PLFAs of forest swamp soil were 34% and 66% higher than freshwater and saline marsh soils, respectively.
31887499	2	46	theme	wetland	348:354	arg1	soils					356:360	three Mississippi River deltaic plain wetland soils	310:360	three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	310:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	6	47	theme	forest	1034:1039	arg1	soil					1047:1050	forest swamp soil	1034:1050	forest swamp soil	1034:1050	Total PLFAs of forest swamp soil were 34% and 66% higher than freshwater and saline marsh soils, respectively.
31887499	3	48	theme	microbial	635:643	arg1	community					645:653	soil microbial community	630:653	soil microbial community	630:653	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	8	49	from	response	1464:1471	arg1	respiration					1485:1495	soil CO2 respiration	1476:1495	soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading	1476:1553	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	2	50	theme	deltaic	334:340	arg1	soils					356:360	three Mississippi River deltaic plain wetland soils	310:360	three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	310:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	1	51	theme	wetland	220:226	arg1	soils					228:232	wetland soils	220:232	wetland soils that contradict thermodynamic predictions	220:274	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	7	52	theme	different	1158:1166	arg1	distribution					1178:1189	different microbial distribution	1158:1189	different microbial distribution	1158:1189	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	8	53	theme	marsh	1522:1526	arg1	ecosystems					1528:1537	forest swamp and marsh ecosystems	1505:1537	ecosystems	1528:1537	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	4	54	theme	swamp	808:812	arg1	soil					821:824	swamp forest soil	808:824	swamp forest soil	808:824	Addition of NO3- promoted CO2 production in swamp forest soil, but inhibited CO2 emission from marsh soils.
31887499	7	55	theme	marsh	1333:1337	arg1	soils					1339:1343	marsh soils	1333:1343	marsh soils	1333:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	2	56	theme	CO2	292:294	arg1	production					296:305	CO2 production	292:305	CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	292:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	7	57	theme	reducers	1319:1326	arg1	proportion					1255:1264	a higher proportion	1246:1264	a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1246:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	3	58	theme	fatty	699:703	arg1	PLFA					711:714	PLFA	711:714	PLFA	711:714	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	3	58	theme	fatty	699:703	arg1	acid					705:708	phosphorus lipid fatty acid	682:708	phosphorus lipid fatty acid (PLFA) method	682:722	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	4	59	theme	CO2	841:843	arg1	emission					845:852	CO2 emission	841:852	CO2 emission	841:852	Addition of NO3- promoted CO2 production in swamp forest soil, but inhibited CO2 emission from marsh soils.
31887499	3	60	theme	phosphorus	682:691	arg1	PLFA					711:714	PLFA	711:714	PLFA	711:714	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	3	60	theme	phosphorus	682:691	arg1	acid					705:708	phosphorus lipid fatty acid	682:708	phosphorus lipid fatty acid (PLFA) method	682:722	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	5	61	theme	compounds	1008:1016	arg1	abundance					986:994	high abundance	981:994	high abundance of phenolic compounds	981:1016	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	7	62	theme	sulfate	1303:1309	arg1	reducers					1319:1326	lower sulfate (SO42-) reducers	1297:1326	lower sulfate (SO42-) reducers	1297:1326	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	3	63	theme	Molecular	515:523	arg1	composition					525:535	Molecular composition	515:535	Molecular composition of dissolved organic matter (DOM) of these soils	515:584	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	7	64	contain	having	1239:1244	arg2	proportion					1255:1264	a higher proportion	1246:1264	a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1246:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	7	64	contain	having	1239:1244	arg1	swamp					1233:1237	the forest swamp	1222:1237	the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1222:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	9	65	theme	coastal	1649:1655	arg1	wetlands					1657:1664	Louisiana coastal wetlands	1639:1664	Louisiana coastal wetlands from river diversions and other sources	1639:1704	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	8	66	theme	inherent	1384:1391	arg1	differences					1393:1403	the inherent differences	1380:1403	the inherent differences in soil DOM and microbial community	1380:1439	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	7	67	theme	NO3-	1279:1282	arg1	reducers					1284:1291	fungi and NO3- reducers	1269:1291	fungi and NO3- reducers	1269:1291	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	7	68	theme	PLFA	1134:1137	arg1	profiles					1139:1146	The PLFA profiles	1130:1146	The PLFA profiles	1130:1146	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	3	69	theme	organic	550:556	arg1	matter					558:563	dissolved organic matter	540:563	dissolved organic matter (DOM) of these soils	540:584	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	3	69	theme	organic	550:556	arg1	DOM					566:568	DOM	566:568	DOM	566:568	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	1	70	theme	Recent	136:141	arg1	studies					143:149	Recent studies	136:149	Recent studies	136:149	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	7	71	theme	fungi	1269:1273	arg1	reducers					1284:1291	fungi and NO3- reducers	1269:1291	fungi and NO3- reducers	1269:1291	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	1	72	from	effect	166:171	arg1	emissions					205:213	carbon gas emissions	194:213	carbon gas emissions from wetland soils that contradict thermodynamic predictions	194:274	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	2	73	theme	levels	444:449	arg1	presence					417:424	the presence	413:424	the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	413:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	0	74	theme	coastal	89:95	arg1	wetlands					97:104	Mexico coastal wetlands	82:104	Mexico coastal wetlands: Phenomena and relationships	82:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	7	75	theme	higher	1248:1253	arg1	proportion					1255:1264	a higher proportion	1246:1264	a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1246:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	9	76	theme	other	1692:1696	arg1	sources					1698:1704	other sources	1692:1704	other sources	1692:1704	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	8	77	theme	microbial	1421:1429	arg1	community					1431:1439	microbial community	1421:1439	microbial community	1421:1439	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	5	78	theme	swamp	909:913	arg1	soil					915:918	swamp soil	909:918	swamp soil	909:918	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	6	79	theme	Total	1019:1023	arg1	PLFAs					1025:1029	Total PLFAs	1019:1029	Total PLFAs of forest swamp soil	1019:1050	Total PLFAs of forest swamp soil were 34% and 66% higher than freshwater and saline marsh soils, respectively.
31887499	2	80	theme	forest	363:368	arg1	freshwater					377:386	freshwater	377:386	freshwater	377:386	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	2	80	theme	forest	363:368	arg1	marshes					399:405	saline marshes	392:405	saline marshes	392:405	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	2	80	theme	forest	363:368	arg1	swamp					370:374	forest swamp	363:374	forest swamp	363:374	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	0	81	theme	anaerobic	10:18	arg1	production					24:33	anaerobic CO2 production	10:33	anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships	10:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	0	82	theme	production	24:33	arg1	response					35:42	anaerobic CO2 production response	10:42	anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships	10:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	5	83	theme	Pyrolysis-GC/MS	872:886	arg1	analysis					888:895	Pyrolysis-GC/MS analysis	872:895	Pyrolysis-GC/MS analysis	872:895	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	7	84	theme	forest	1226:1231	arg1	swamp					1233:1237	the forest swamp	1222:1237	the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1222:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	6	85	theme	swamp	1041:1045	arg1	soil					1047:1050	forest swamp soil	1034:1050	forest swamp soil	1034:1050	Total PLFAs of forest swamp soil were 34% and 66% higher than freshwater and saline marsh soils, respectively.
31887499	6	86	theme	marsh	1103:1107	arg1	soils					1109:1113	marsh soils	1103:1113	marsh soils	1103:1113	Total PLFAs of forest swamp soil were 34% and 66% higher than freshwater and saline marsh soils, respectively.
31887499	2	87	theme	different	429:437	arg1	levels					444:449	different NO3- levels	429:449	different NO3- levels (0.2, 2.0, and 3.2 mM)	429:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	8	88	theme	soil	1476:1479	arg1	respiration					1485:1495	soil CO2 respiration	1476:1495	soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading	1476:1553	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	0	89	theme	nitrate	56:62	arg1	levels					64:69	elevated nitrate levels	47:69	elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships	47:133	Exploring anaerobic CO2 production response to elevated nitrate levels in Gulf of Mexico coastal wetlands: Phenomena and relationships.
31887499	5	90	theme	marsh	965:969	arg1	soils					971:975	both marsh soils	960:975	both marsh soils	960:975	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	7	91	theme	salinity	1199:1206	arg1	gradient					1208:1215	a salinity gradient	1197:1215	a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils	1197:1343	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	5	92	contain	had	977:979	arg2	abundance					986:994	high abundance	981:994	high abundance of phenolic compounds	981:1016	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	5	92	contain	had	977:979	arg1	soils					971:975	both marsh soils	960:975	both marsh soils	960:975	Pyrolysis-GC/MS analysis showed that swamp soil contained more polysaccharides, whereas both marsh soils had high abundance of phenolic compounds.
31887499	9	93	from	diversions	1677:1686	arg1	wetlands					1657:1664	Louisiana coastal wetlands	1639:1664	Louisiana coastal wetlands from river diversions and other sources	1639:1704	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	9	93	from	diversions	1677:1686	arg1	management					1716:1725	their management	1710:1725	their management	1710:1725	These differences should be considered in determining the fate of nitrate entering Louisiana coastal wetlands from river diversions and other sources and their management.
31887499	8	94	theme	forest	1505:1510	arg1	swamp					1512:1516	forest swamp and marsh ecosystems	1505:1537	swamp	1512:1516	Overall, the study indicated that the inherent differences in soil DOM and microbial community led to the contrasting response in soil CO2 respiration between forest swamp and marsh ecosystems to NO3- loading.
31887499	2	95	dep	soils	356:360	arg1	freshwater					377:386	freshwater	377:386	freshwater	377:386	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	2	95	dep	soils	356:360	arg1	marshes					399:405	saline marshes	392:405	saline marshes	392:405	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	2	95	dep	soils	356:360	arg1	swamp					370:374	forest swamp	363:374	forest swamp	363:374	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
31887499	1	96	theme	gas	201:203	arg1	emissions					205:213	carbon gas emissions	194:213	carbon gas emissions from wetland soils that contradict thermodynamic predictions	194:274	Recent studies have shown the effect of nitrate (NO3-) on carbon gas emissions from wetland soils that contradict thermodynamic predictions.
31887499	7	97	theme	microbial	1168:1176	arg1	distribution					1178:1189	different microbial distribution	1158:1189	different microbial distribution	1158:1189	The PLFA profiles indicated different microbial distribution along a salinity gradient with the forest swamp having a higher proportion of fungi and NO3- reducers but lower sulfate (SO42-) reducers than marsh soils.
31887499	3	98	theme	soil	630:633	arg1	community					645:653	soil microbial community	630:653	soil microbial community	630:653	Molecular composition of dissolved organic matter (DOM) of these soils was investigated using pyrolysis-GC/MS, and soil microbial community was characterized based on phosphorus lipid fatty acid (PLFA) method to elucidate the underlying mechanisms.
31887499	2	99	theme	plain	342:346	arg1	soils					356:360	three Mississippi River deltaic plain wetland soils	310:360	three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM)	310:472	In this study, CO2 production in three Mississippi River deltaic plain wetland soils (forest swamp, freshwater and saline marshes) with the presence of different NO3- levels (0.2, 2.0, and 3.2 mM) was evaluated in an anaerobic microcosm.
29991350	2	0	theme	Mediterranean	345:357	arg1	intervals					373:381	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	14	1	theme	metagenomic	2404:2414	arg1	approaches					2392:2401	approaches	2392:2401	approaches (metagenomic assembly and recruitment)	2392:2440	Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.
29991350	14	1	theme	metagenomic	2404:2414	arg1	assembly					2416:2423	metagenomic assembly	2404:2423	metagenomic assembly	2404:2423	Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.
29991350	10	2	theme	depth-related	1513:1525	arg1	specialization					1527:1540	A strong depth-related specialization	1504:1540	A strong depth-related specialization	1504:1540	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	13	3	theme	water	2195:2199	arg1	column					2201:2206	the water column	2191:2206	the water column	2191:2206	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	4	4	theme	water	836:840	arg1	column					842:847	the stratified photic water column	814:847	the stratified photic water column	814:847	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	7	5	theme	winter	1055:1060	arg1	period					1069:1074	the winter mixing period	1051:1074	the winter mixing period	1051:1074	During the winter mixing period, only some groups of bloomers such as Pseudomonas were favored.
29991350	3	6	theme	new	538:540	arg1	MAGs					572:575	MAGs	572:575	MAGs	572:575	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	3	6	theme	new	538:540	arg1	genomes					563:569	94 new metagenome-assembled genomes	535:569	94 new metagenome-assembled genomes (MAGs) from these metagenomes	535:599	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	1	7	theme	strong	182:187	arg1	gradients					205:213	strong physicochemical gradients	182:213	strong physicochemical gradients	182:213	BACKGROUND The photic zone of aquatic habitats is subjected to strong physicochemical gradients.
29991350	8	8	theme	most	1149:1152	arg1	microbes					1154:1161	most microbes	1149:1161	most microbes	1149:1161	Although most microbes appeared in both seasons, some groups like the SAR116 clade and some Bacteroidetes and Verrucomicrobia seemed to disappear during the mixing period.
29991350	12	9	contain	has	1969:1971	arg1	study					1963:1967	this study	1958:1967	this study	1958:1967	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	12	9	contain	has	1969:1971	arg2	implications					1982:1993	profound implications	1973:1993	profound implications for our understanding of how marine microbial communities vary with depth within the photic zone	1973:2090	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	10	10	theme	specific	1691:1698	arg1	polysaccharides					1700:1714	specific polysaccharides	1691:1714	specific polysaccharides	1691:1714	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	12	11	theme	microbial	2031:2039	arg1	communities					2041:2051	marine microbial communities	2024:2051	marine microbial communities	2024:2051	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	2	12	theme	fine-scale	231:240	arg1	variations					242:251	the fine-scale variations	227:251	the fine-scale variations in the marine microbiome	227:276	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	9	13	theme	deeper	1433:1438	arg1	layers					1440:1445	deeper layers	1433:1445	deeper layers within the photic zone during the stratification period	1433:1501	Furthermore, we found that some microbes previously considered seasonal (e.g., Archaea or Actinobacteria) were living in deeper layers within the photic zone during the stratification period.
29991350	13	14	from	depth	2352:2356	arg1	samples					2323:2329	samples	2323:2329	samples from only one single depth	2323:2356	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	2	15	theme	marine	260:265	arg1	microbiome					267:276	the marine microbiome	256:276	the marine microbiome	256:276	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	1	16	theme	photic	134:139	arg1	zone					141:144	The photic zone	130:144	The photic zone of aquatic habitats	130:164	BACKGROUND The photic zone of aquatic habitats is subjected to strong physicochemical gradients.
29991350	2	17	theme	photic	480:485	arg1	column					493:498	the photic water column	476:498	the photic water column	476:498	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	0	18	theme	mixed	61:65	arg1	columns					73:79	the Mediterranean stratified and mixed water columns	28:79	the Mediterranean stratified and mixed water columns	28:79	Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.
29991350	11	19	dep	sequences	1727:1735	arg1	green					1738:1742	green	1738:1742	green	1738:1742	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	11	19	dep	sequences	1727:1735	arg1	blue					1747:1750	blue	1747:1750	blue	1747:1750	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	9	20	theme	photic	1458:1463	arg1	zone					1465:1468	the photic zone	1454:1468	the photic zone during the stratification period	1454:1501	Furthermore, we found that some microbes previously considered seasonal (e.g., Archaea or Actinobacteria) were living in deeper layers within the photic zone during the stratification period.
29991350	12	21	theme	profound	1973:1980	arg1	implications					1982:1993	profound implications	1973:1993	profound implications for our understanding of how marine microbial communities vary with depth within the photic zone	1973:2090	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	0	22	theme	columns	73:79	arg1	profile					17:23	Fine metagenomic profile	0:23	Fine metagenomic profile of the Mediterranean stratified and mixed water columns	0:79	Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.
29991350	1	23	theme	habitats	157:164	arg1	zone					141:144	The photic zone	130:144	The photic zone of aquatic habitats	130:164	BACKGROUND The photic zone of aquatic habitats is subjected to strong physicochemical gradients.
29991350	14	24	dep	approaches	2392:2401	arg1	approaches					2392:2401	approaches	2392:2401	approaches (metagenomic assembly and recruitment)	2392:2440	Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.
29991350	14	24	dep	approaches	2392:2401	arg1	assembly					2416:2423	metagenomic assembly	2404:2423	metagenomic assembly	2404:2423	Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.
29991350	14	24	dep	approaches	2392:2401	arg1	recruitment					2429:2439	recruitment	2429:2439	recruitment	2429:2439	Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.
29991350	4	25	from	differences	746:756	arg1	composition					775:785	the microbial composition	761:785	the microbial composition of different layers	761:805	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	9	26	theme	stratification	1481:1494	arg1	period					1496:1501	the stratification period	1477:1501	the stratification period	1477:1501	Furthermore, we found that some microbes previously considered seasonal (e.g., Archaea or Actinobacteria) were living in deeper layers within the photic zone during the stratification period.
29991350	4	27	dep	RESULTS	707:713	arg1	showed					727:732	showed	727:732	showed significant differences in the microbial composition of different layers within the stratified photic water column	727:847	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	11	28	theme	microbe	1833:1839	arg1	taxonomy					1817:1824	the taxonomy	1813:1824	the taxonomy of the microbe in which they were found	1813:1864	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	2	29	from	variations	242:251	arg1	microbiome					267:276	the marine microbiome	256:276	the marine microbiome	256:276	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	12	30	dep	CONCLUSIONS	1886:1896	arg1	has					1969:1971	has	1969:1971	has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified	1969:2106	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	3	31	from	metagenomes	589:599	arg1	MAGs					572:575	MAGs	572:575	MAGs	572:575	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	3	31	from	metagenomes	589:599	arg1	genomes					563:569	94 new metagenome-assembled genomes	535:569	94 new metagenome-assembled genomes (MAGs) from these metagenomes	535:599	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	0	32	theme	Fine	0:3	arg1	profile					17:23	Fine metagenomic profile	0:23	Fine metagenomic profile of the Mediterranean stratified and mixed water columns	0:79	Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.
29991350	11	33	located	found	1860:1864	arg1	microbe					1833:1839	the microbe	1829:1839	the microbe in which they were found	1829:1864	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	11	33	located	found	1860:1864	arg2	they					1850:1853	they	1850:1853	they	1850:1853	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	13	34	theme	samples	2160:2166	arg1	importance					2135:2144	the importance	2131:2144	the importance of collecting samples at different depths in the water column	2131:2206	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	2	35	theme	strong	402:407	arg1	stratification					409:422	strong stratification	402:422	strong stratification	402:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	9	36	dep	Archaea	1391:1397	arg1	e.g.					1385:1388	e.g.	1385:1388	e.g.	1385:1388	Furthermore, we found that some microbes previously considered seasonal (e.g., Archaea or Actinobacteria) were living in deeper layers within the photic zone during the stratification period.
29991350	10	37	theme	functional	1604:1613	arg1	level					1615:1619	the functional level	1600:1619	the functional level	1600:1619	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	7	38	theme	bloomers	1097:1104	arg1	bloomers					1097:1104	bloomers	1097:1104	bloomers such as Pseudomonas	1097:1124	During the winter mixing period, only some groups of bloomers such as Pseudomonas were favored.
29991350	7	38	theme	bloomers	1097:1104	arg1	Pseudomonas					1114:1124	Pseudomonas	1114:1124	Pseudomonas	1114:1124	During the winter mixing period, only some groups of bloomers such as Pseudomonas were favored.
29991350	7	38	theme	bloomers	1097:1104	arg1	groups					1087:1092	only some groups	1077:1092	only some groups of bloomers such as Pseudomonas	1077:1124	During the winter mixing period, only some groups of bloomers such as Pseudomonas were favored.
29991350	14	39	theme	other	2468:2472	arg1	studies					2486:2492	other metagenomic studies	2468:2492	other metagenomic studies	2468:2492	Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.
29991350	6	40	theme	clade	1001:1005	arg1	members					980:986	members	980:986	members of the SAR11 clade	980:1005	Only a few such as members of the SAR11 clade appeared at all depths (eurybathic).
29991350	4	41	theme	stratified	818:827	arg1	column					842:847	the stratified photic water column	814:847	the stratified photic water column	814:847	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	10	42	theme	different	1638:1646	arg1	clades					1648:1653	the different clades	1634:1653	the different clades	1634:1653	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	0	43	theme	stratified	46:55	arg1	columns					73:79	the Mediterranean stratified and mixed water columns	28:79	the Mediterranean stratified and mixed water columns	28:79	Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.
29991350	3	44	theme	microbes	644:651	arg1	distribution					617:628	the distribution	613:628	the distribution of key marine microbes within the photic zone using metagenomic recruitment	613:704	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	11	45	theme	narrow	1765:1770	arg1	distributions					1778:1790	narrow depth distributions	1765:1790	narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth	1765:1883	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	3	46	theme	key	633:635	arg1	microbes					644:651	key marine microbes	633:651	key marine microbes	633:651	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	4	47	theme	different	790:798	arg1	layers					800:805	different layers	790:805	different layers	790:805	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	2	48	theme	depth	367:371	arg1	intervals					373:381	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	13	49	theme	global	2280:2285	arg1	studies					2294:2300	global marine studies	2280:2300	global marine studies that most often take samples from only one single depth	2280:2356	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	2	50	theme	at	359:360	arg1	intervals					373:381	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	2	51	from	location	329:336	arg1	samples					445:451	two more samples	436:451	two more samples during the winter	436:469	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	2	51	from	location	329:336	arg1	intervals					373:381	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	2	51	from	location	329:336	arg1	samples					298:304	seven samples	292:304	seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification	292:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	7	52	theme	mixing	1062:1067	arg1	period					1069:1074	the winter mixing period	1051:1074	the winter mixing period	1051:1074	During the winter mixing period, only some groups of bloomers such as Pseudomonas were favored.
29991350	12	53	from	location	1927:1934	arg1	Mediterranean					1943:1955	Mediterranean	1943:1955	Mediterranean	1943:1955	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	10	54	theme	strong	1506:1511	arg1	specialization					1527:1540	A strong depth-related specialization	1504:1540	A strong depth-related specialization	1504:1540	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	13	55	from	depths	2181:2186	arg1	importance					2135:2144	the importance	2131:2144	the importance of collecting samples at different depths in the water column	2131:2206	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	13	56	theme	important	2252:2260	arg1	ramifications					2262:2274	important ramifications	2252:2274	important ramifications for global marine studies that most often take samples from only one single depth	2252:2356	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	12	57	theme	single	1920:1925	arg1	location					1927:1934	a single location	1918:1934	a single location in the Mediterranean	1918:1955	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	4	58	theme	photic	829:834	arg1	column					842:847	the stratified photic water column	814:847	the stratified photic water column	814:847	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	3	59	theme	metagenomic	682:692	arg1	recruitment					694:704	metagenomic recruitment	682:704	metagenomic recruitment	682:704	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	2	60	theme	single	313:318	arg1	location					329:336	a single offshore location	311:336	a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification	311:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	10	61	theme	polysaccharides	1700:1714	arg1	uptake					1681:1686	uptake	1681:1686	uptake	1681:1686	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	10	61	theme	polysaccharides	1700:1714	arg1	manipulation					1664:1675	manipulation	1664:1675	manipulation	1664:1675	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	1	62	theme	physicochemical	189:203	arg1	gradients					205:213	strong physicochemical gradients	182:213	strong physicochemical gradients	182:213	BACKGROUND The photic zone of aquatic habitats is subjected to strong physicochemical gradients.
29991350	5	63	theme	discreet	898:905	arg1	layers					918:923	discreet horizontal layers	898:923	discreet horizontal layers of no more than 30 m (stenobathic)	898:958	The majority of microorganisms were confined to discreet horizontal layers of no more than 30 m (stenobathic).
29991350	10	64	theme	taxonomic	1572:1580	arg1	level					1582:1586	the taxonomic level	1568:1586	the taxonomic level	1568:1586	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	5	65	theme	microorganisms	866:879	arg1	majority					854:861	The majority	850:861	The majority of microorganisms	850:879	The majority of microorganisms were confined to discreet horizontal layers of no more than 30 m (stenobathic).
29991350	12	66	theme	marine	2024:2029	arg1	communities					2041:2051	marine microbial communities	2024:2051	marine microbial communities	2024:2051	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	3	67	theme	metagenome-assembled	542:561	arg1	MAGs					572:575	MAGs	572:575	MAGs	572:575	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	3	67	theme	metagenome-assembled	542:561	arg1	genomes					563:569	94 new metagenome-assembled genomes	535:569	94 new metagenome-assembled genomes (MAGs) from these metagenomes	535:599	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	5	68	theme	horizontal	907:916	arg1	layers					918:923	discreet horizontal layers	898:923	discreet horizontal layers of no more than 30 m (stenobathic)	898:958	The majority of microorganisms were confined to discreet horizontal layers of no more than 30 m (stenobathic).
29991350	9	69	dep	seasonal	1375:1382	arg1	Archaea					1391:1397	Archaea	1391:1397	Archaea	1391:1397	Furthermore, we found that some microbes previously considered seasonal (e.g., Archaea or Actinobacteria) were living in deeper layers within the photic zone during the stratification period.
29991350	9	69	dep	seasonal	1375:1382	arg1	Actinobacteria					1402:1415	Actinobacteria	1402:1415	Actinobacteria	1402:1415	Furthermore, we found that some microbes previously considered seasonal (e.g., Archaea or Actinobacteria) were living in deeper layers within the photic zone during the stratification period.
29991350	6	70	theme	SAR11	995:999	arg1	clade					1001:1005	the SAR11 clade	991:1005	the SAR11 clade	991:1005	Only a few such as members of the SAR11 clade appeared at all depths (eurybathic).
29991350	0	71	theme	water	67:71	arg1	columns					73:79	the Mediterranean stratified and mixed water columns	28:79	the Mediterranean stratified and mixed water columns	28:79	Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.
29991350	13	72	theme	seasonal	2223:2230	arg1	variations					2232:2241	seasonal variations	2223:2241	seasonal variations	2223:2241	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	13	73	theme	different	2171:2179	arg1	depths					2181:2186	different depths	2171:2186	different depths	2171:2186	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	10	74	dep	manipulation	1664:1675	arg1	the					1660:1662	the	1660:1662	the	1660:1662	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	1	75	theme	aquatic	149:155	arg1	habitats					157:164	aquatic habitats	149:164	aquatic habitats	149:164	BACKGROUND The photic zone of aquatic habitats is subjected to strong physicochemical gradients.
29991350	13	76	from	importance	2135:2144	arg1	column					2201:2206	the water column	2191:2206	the water column	2191:2206	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	11	77	theme	Rhodopsin	1717:1725	arg1	sequences					1727:1735	Rhodopsin sequences	1717:1735	Rhodopsin sequences (green or blue)	1717:1751	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	4	78	theme	significant	734:744	arg1	differences					746:756	significant differences	734:756	significant differences in the microbial composition of different layers	734:805	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	11	79	theme	depth	1772:1776	arg1	distributions					1778:1790	narrow depth distributions	1765:1790	narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth	1765:1883	Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.
29991350	2	80	theme	water	487:491	arg1	column					493:498	the photic water column	476:498	the photic water column	476:498	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	1	81	dep	BACKGROUND	119:128	arg1	subjected					169:177	subjected	169:177	is subjected to strong physicochemical gradients	166:213	BACKGROUND The photic zone of aquatic habitats is subjected to strong physicochemical gradients.
29991350	0	82	theme	metagenomic	5:15	arg1	profile					17:23	Fine metagenomic profile	0:23	Fine metagenomic profile of the Mediterranean stratified and mixed water columns	0:79	Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.
29991350	5	83	theme	more	931:934	arg1	layers					918:923	discreet horizontal layers	898:923	discreet horizontal layers of no more than 30 m (stenobathic)	898:958	The majority of microorganisms were confined to discreet horizontal layers of no more than 30 m (stenobathic).
29991350	13	84	theme	collecting	2149:2158	arg1	samples					2160:2166	collecting samples	2149:2166	collecting samples	2149:2166	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	13	85	theme	single	2345:2350	arg1	depth					2352:2356	only one single depth	2336:2356	only one single depth	2336:2356	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	2	86	theme	stratification	409:422	arg1	period					392:397	a period	390:397	a period of strong stratification	390:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	0	87	theme	Mediterranean	32:44	arg1	columns					73:79	the Mediterranean stratified and mixed water columns	28:79	the Mediterranean stratified and mixed water columns	28:79	Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.
29991350	14	88	theme	metagenomic	2474:2484	arg1	studies					2486:2492	other metagenomic studies	2468:2492	other metagenomic studies	2468:2492	Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.
29991350	4	89	theme	layers	800:805	arg1	composition					775:785	the microbial composition	761:785	the microbial composition of different layers	761:805	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	13	90	contain	have	2247:2250	arg1	results					2113:2119	Our results	2109:2119	Our results	2109:2119	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	13	90	contain	have	2247:2250	arg2	ramifications					2262:2274	important ramifications	2252:2274	important ramifications for global marine studies that most often take samples from only one single depth	2252:2356	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	2	91	from	intervals	373:381	arg1	at					359:360	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	2	91	from	intervals	373:381	arg1	15 m					362:365	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	2	91	from	intervals	373:381	arg1	depth					367:371	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	3	92	theme	marine	637:642	arg1	microbes					644:651	key marine microbes	633:651	key marine microbes	633:651	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	10	93	located	detected	1546:1553	arg2	specialization					1527:1540	A strong depth-related specialization	1504:1540	A strong depth-related specialization	1504:1540	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	10	93	located	detected	1546:1553	arg1	level					1582:1586	the taxonomic level	1568:1586	the taxonomic level	1568:1586	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	10	93	located	detected	1546:1553	arg1	clades					1648:1653	the different clades	1634:1653	the different clades	1634:1653	A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides.
29991350	13	94	theme	marine	2287:2292	arg1	studies					2294:2300	global marine studies	2280:2300	global marine studies that most often take samples from only one single depth	2280:2356	Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth.
29991350	8	95	theme	mixing	1297:1302	arg1	period					1304:1309	the mixing period	1293:1309	the mixing period	1293:1309	Although most microbes appeared in both seasons, some groups like the SAR116 clade and some Bacteroidetes and Verrucomicrobia seemed to disappear during the mixing period.
29991350	4	96	theme	microbial	765:773	arg1	composition					775:785	the microbial composition	761:785	the microbial composition of different layers	761:805	RESULTS Our results showed significant differences in the microbial composition of different layers within the stratified photic water column.
29991350	2	97	theme	offshore	320:327	arg1	location					329:336	a single offshore location	311:336	a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification	311:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29991350	8	98	theme	SAR116	1210:1215	arg1	clade					1217:1221	the SAR116 clade	1206:1221	the SAR116 clade	1206:1221	Although most microbes appeared in both seasons, some groups like the SAR116 clade and some Bacteroidetes and Verrucomicrobia seemed to disappear during the mixing period.
29991350	3	99	theme	photic	664:669	arg1	zone					671:674	the photic zone	660:674	the photic zone using metagenomic recruitment	660:704	We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.
29991350	12	100	theme	photic	2080:2085	arg1	zone					2087:2090	the photic zone	2076:2090	the photic zone	2076:2090	CONCLUSIONS Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified.
29991350	2	101	theme	15 m	362:365	arg1	intervals					373:381	the Mediterranean at 15 m depth intervals	341:381	the Mediterranean at 15 m depth intervals during a period of strong stratification	341:422	To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed.
29524488	5	0	theme	single-layer	866:877	arg1	microspheres					879:890	core-shell and single-layer microspheres	851:890	core-shell and single-layer microspheres obtained from XPS and IR analysis	851:924	The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis.
29524488	7	1	theme	pendant	1379:1385	arg1	groups					1387:1392	cinnamate pendant groups	1369:1392	cinnamate pendant groups of the shell material	1369:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	7	1	theme	pendant	1379:1385	arg1	material					1407:1414	the shell material	1397:1414	the shell material	1397:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	2	2	theme	release	399:405	arg1	regulation					377:386	further regulation	369:386	further regulation of insulin release	369:405	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	3	3	from	network	605:611	arg1	release					551:557	basal and bolus insulin release	527:557	release	551:557	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	4	4	theme	two-step	664:671	arg1	method					705:710	a two-step high-speed shear-emulsification method	662:710	a two-step high-speed shear-emulsification method	662:710	Core-shell microspheres were fabricated through a two-step high-speed shear-emulsification method.
29524488	6	5	theme	glucose	1119:1125	arg1	concentration					1127:1139	different glucose concentration	1109:1139	different glucose concentration	1109:1139	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	6	6	theme	In	927:928	arg1	test					952:955	In vitro insulin release test	927:955	In vitro insulin release test	927:955	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	2	7	theme	insulin	391:397	arg1	release					399:405	insulin release	391:405	insulin release	391:405	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	2	8	from	paid	361:364	arg1	systems					327:333	glucose-responsive insulin delivery systems	291:333	glucose-responsive insulin delivery systems	291:333	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	5	9	from	differences	807:817	arg1	composition					831:841	chemical composition	822:841	chemical composition	822:841	The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis.
29524488	0	10	theme	A-sugar	112:118	arg1	affinity					120:127	concanavalin A-sugar affinity	99:127	concanavalin A-sugar affinity	99:127	Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.
29524488	6	11	dep	concentration	1127:1139	arg1	response					1097:1104	response	1097:1104	response	1097:1104	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	4	12	theme	shear-emulsification	684:703	arg1	method					705:710	a two-step high-speed shear-emulsification method	662:710	a two-step high-speed shear-emulsification method	662:710	Core-shell microspheres were fabricated through a two-step high-speed shear-emulsification method.
29524488	0	13	theme	concanavalin	99:110	arg1	affinity					120:127	concanavalin A-sugar affinity	99:127	concanavalin A-sugar affinity	99:127	Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.
29524488	8	14	theme	dichroism	1505:1513	arg1	analysis					1515:1522	fluorescence and circular dichroism analysis	1479:1522	fluorescence and circular dichroism analysis	1479:1522	The released insulin was proved to remain active according to fluorescence and circular dichroism analysis.
29524488	7	15	theme	material	1407:1414	arg1	groups					1387:1392	cinnamate pendant groups	1369:1392	cinnamate pendant groups of the shell material	1369:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	7	15	theme	material	1407:1414	arg1	material					1407:1414	the shell material	1397:1414	the shell material	1397:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	7	16	theme	shell	1401:1405	arg1	material					1407:1414	the shell material	1397:1414	the shell material	1397:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	9	17	theme	cell	1533:1536	arg1	assessment					1548:1557	The HDF cell viability assessment	1525:1557	The HDF cell viability assessment	1525:1557	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	4	18	theme	high-speed	673:682	arg1	method					705:710	a two-step high-speed shear-emulsification method	662:710	a two-step high-speed shear-emulsification method	662:710	Core-shell microspheres were fabricated through a two-step high-speed shear-emulsification method.
29524488	7	19	theme	photo-induced	1338:1350	arg1	cycloaddition					1352:1364	the photo-induced cycloaddition	1334:1364	the photo-induced cycloaddition of cinnamate pendant groups of the shell material	1334:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	3	20	theme	bolus	537:541	arg1	release					551:557	basal and bolus insulin release	527:557	release	551:557	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	7	21	theme	insulin	1243:1249	arg1	rate					1259:1262	insulin release rate	1243:1262	insulin release rate	1243:1262	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	8	22	theme	released	1421:1428	arg1	insulin					1430:1436	The released insulin	1417:1436	The released insulin	1417:1436	The released insulin was proved to remain active according to fluorescence and circular dichroism analysis.
29524488	3	23	theme	A-polysaccharides	587:603	arg1	network					605:611	glucose-responsive Con A-polysaccharides network	564:611	glucose-responsive Con A-polysaccharides network	564:611	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	1	24	theme	resistance	198:207	arg1	heterogeneity					173:185	the heterogeneity	169:185	the heterogeneity of insulin resistance between patients	169:224	Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy.
29524488	6	25	theme	different	1109:1117	arg1	concentration					1127:1139	different glucose concentration	1109:1139	different glucose concentration	1109:1139	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	7	26	theme	release	1251:1257	arg1	rate					1259:1262	insulin release rate	1243:1262	insulin release rate	1243:1262	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	2	27	theme	delivery	318:325	arg1	systems					327:333	glucose-responsive insulin delivery systems	291:333	glucose-responsive insulin delivery systems	291:333	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	9	28	theme	viability	1538:1546	arg1	assessment					1548:1557	The HDF cell viability assessment	1525:1557	The HDF cell viability assessment	1525:1557	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	3	29	theme	photo-crosslinkable	483:501	arg1	layer					509:513	a photo-crosslinkable shell layer	481:513	a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network	481:611	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	5	30	theme	IR	914:915	arg1	analysis					917:924	IR analysis	914:924	IR analysis	914:924	The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis.
29524488	7	31	theme	groups	1387:1392	arg1	cycloaddition					1352:1364	the photo-induced cycloaddition	1334:1364	the photo-induced cycloaddition of cinnamate pendant groups of the shell material	1334:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	6	32	theme	burst	1163:1167	arg1	release					1169:1175	much lower burst release	1152:1175	much lower burst release	1152:1175	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	9	33	contain	possessed	1602:1610	arg2	cytotoxicity					1624:1635	no in vitro cytotoxicity	1612:1635	no in vitro cytotoxicity	1612:1635	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	9	33	contain	possessed	1602:1610	arg1	microspheres					1589:1600	the core-shell microspheres	1574:1600	the core-shell microspheres	1574:1600	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	2	34	theme	individual	415:424	arg1	requirements					426:437	individual requirements	415:437	individual requirements	415:437	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	0	35	theme	bolus	20:24	arg1	release					34:40	Regulated basal and bolus insulin release	0:40	release	34:40	Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.
29524488	6	36	theme	single-layer	1191:1202	arg1	microspheres					1204:1215	single-layer microspheres	1191:1215	single-layer microspheres without shell	1191:1229	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	6	37	theme	core-shell	975:984	arg1	microspheres					986:997	the core-shell microspheres	971:997	the core-shell microspheres with or without light-irradiation	971:1031	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	1	38	theme	insulin	190:196	arg1	resistance					198:207	insulin resistance	190:207	insulin resistance	190:207	Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy.
29524488	6	39	dep	In	927:928	arg1	vitro					930:934	vitro	930:934	vitro	930:934	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	1	40	theme	more	236:239	arg1	benefits					241:248	more benefits	236:248	more benefits	236:248	Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy.
29524488	3	41	theme	insulin	543:549	arg1	release					551:557	basal and bolus insulin release	527:557	release	551:557	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	8	42	theme	fluorescence	1479:1490	arg1	analysis					1515:1522	fluorescence and circular dichroism analysis	1479:1522	fluorescence and circular dichroism analysis	1479:1522	The released insulin was proved to remain active according to fluorescence and circular dichroism analysis.
29524488	3	43	theme	shell	503:507	arg1	layer					509:513	a photo-crosslinkable shell layer	481:513	a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network	481:611	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	0	44	theme	insulin	26:32	arg1	release					34:40	Regulated basal and bolus insulin release	0:40	release	34:40	Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.
29524488	6	45	theme	insulin	1078:1084	arg1	release					1086:1092	basal insulin release	1072:1092	basal insulin release	1072:1092	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	0	46	from	microspheres	77:88	arg1	basal					10:14	basal	10:14	basal	10:14	Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.
29524488	0	47	theme	glucose-responsive	47:64	arg1	microspheres					77:88	glucose-responsive core-shell microspheres	47:88	glucose-responsive core-shell microspheres	47:88	Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.
29524488	6	48	theme	basal	1072:1076	arg1	release					1086:1092	basal insulin release	1072:1092	basal insulin release	1072:1092	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	1	49	gly	heterogeneity	173:185	arg1	resistance					198:207	insulin resistance	190:207	insulin resistance	190:207	Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy.
29524488	9	50	theme	HDF	1529:1531	arg1	assessment					1548:1557	The HDF cell viability assessment	1525:1557	The HDF cell viability assessment	1525:1557	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	1	51	theme	Individual	130:139	arg1	therapy					149:155	Individual insulin therapy	130:155	Individual insulin therapy considering the heterogeneity of insulin resistance between patients	130:224	Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy.
29524488	4	52	theme	Core-shell	614:623	arg1	microspheres					625:636	Core-shell microspheres	614:636	Core-shell microspheres	614:636	Core-shell microspheres were fabricated through a two-step high-speed shear-emulsification method.
29524488	5	53	theme	core-shell	765:774	arg1	structure					776:784	the core-shell structure	761:784	the core-shell structure	761:784	The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis.
29524488	9	54	dep	in	1615:1616	arg1	vitro					1618:1622	vitro	1618:1622	vitro	1618:1622	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	7	55	theme	cinnamate	1369:1377	arg1	groups					1387:1392	cinnamate pendant groups	1369:1392	cinnamate pendant groups of the shell material	1369:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	7	55	theme	cinnamate	1369:1377	arg1	material					1407:1414	the shell material	1397:1414	the shell material	1397:1414	Meanwhile, insulin release rate and amount could be further decreased upon light-irradiation owing to the photo-induced cycloaddition of cinnamate pendant groups of the shell material.
29524488	1	56	theme	insulin	141:147	arg1	therapy					149:155	Individual insulin therapy	130:155	Individual insulin therapy considering the heterogeneity of insulin resistance between patients	130:224	Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy.
29524488	2	57	from	systems	327:333	arg1	paid					361:364	paid	361:364	paid	361:364	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	6	58	theme	release	944:950	arg1	test					952:955	In vitro insulin release test	927:955	In vitro insulin release test	927:955	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	2	59	theme	insulin	310:316	arg1	systems					327:333	glucose-responsive insulin delivery systems	291:333	glucose-responsive insulin delivery systems	291:333	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	6	60	theme	lower	1157:1161	arg1	release					1169:1175	much lower burst release	1152:1175	much lower burst release	1152:1175	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	2	61	theme	further	369:375	arg1	regulation					377:386	further regulation	369:386	further regulation of insulin release	369:405	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	9	62	theme	in	1615:1616	arg1	cytotoxicity					1624:1635	no in vitro cytotoxicity	1612:1635	no in vitro cytotoxicity	1612:1635	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	1	63	theme	conventional	255:266	arg1	therapy					268:274	conventional therapy	255:274	conventional therapy	255:274	Individual insulin therapy considering the heterogeneity of insulin resistance between patients may bring more benefits than conventional therapy.
29524488	6	64	theme	insulin	936:942	arg1	test					952:955	In vitro insulin release test	927:955	In vitro insulin release test	927:955	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	2	65	theme	glucose-responsive	291:308	arg1	systems					327:333	glucose-responsive insulin delivery systems	291:333	glucose-responsive insulin delivery systems	291:333	Therefore, in glucose-responsive insulin delivery systems, more attention should be paid on further regulation of insulin release to meet individual requirements.
29524488	8	66	theme	circular	1496:1503	arg1	dichroism					1505:1513	circular dichroism	1496:1513	circular dichroism	1496:1513	The released insulin was proved to remain active according to fluorescence and circular dichroism analysis.
29524488	3	67	theme	basal	527:531	arg1	release					551:557	basal and bolus insulin release	527:557	release	551:557	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	5	68	theme	core-shell	851:860	arg1	microspheres					879:890	core-shell and single-layer microspheres	851:890	core-shell and single-layer microspheres obtained from XPS and IR analysis	851:924	The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis.
29524488	3	69	theme	glucose-responsive	564:581	arg1	network					605:611	glucose-responsive Con A-polysaccharides network	564:611	glucose-responsive Con A-polysaccharides network	564:611	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	0	70	theme	core-shell	66:75	arg1	microspheres					77:88	glucose-responsive core-shell microspheres	47:88	glucose-responsive core-shell microspheres	47:88	Regulated basal and bolus insulin release from glucose-responsive core-shell microspheres based on concanavalin A-sugar affinity.
29524488	6	71	theme	corresponding	1048:1060	arg1	bolus					1062:1066	corresponding bolus	1048:1066	corresponding bolus	1048:1066	In vitro insulin release test revealed that the core-shell microspheres with or without light-irradiation could maintain corresponding bolus and basal insulin release in response to different glucose concentration but enable much lower burst release compared with single-layer microspheres without shell.
29524488	9	72	theme	core-shell	1578:1587	arg1	microspheres					1589:1600	the core-shell microspheres	1574:1600	the core-shell microspheres	1574:1600	The HDF cell viability assessment suggested that the core-shell microspheres possessed no in vitro cytotoxicity.
29524488	3	73	theme	Con	583:585	arg1	network					605:611	glucose-responsive Con A-polysaccharides network	564:611	glucose-responsive Con A-polysaccharides network	564:611	Our study shows the feasibility of using a photo-crosslinkable shell layer to regulate basal and bolus insulin release from glucose-responsive Con A-polysaccharides network.
29524488	5	74	theme	chemical	822:829	arg1	composition					831:841	chemical composition	822:841	chemical composition	822:841	The morphology was observed by SEM and TEM, and the core-shell structure was confirmed by the differences in chemical composition between core-shell and single-layer microspheres obtained from XPS and IR analysis.
30675753	3	0	theme	Synechocystis	726:738	arg1	sp					740:741	the unicellular Synechocystis sp	710:741	the unicellular Synechocystis sp	710:741	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	9	1	theme	cyanobacterial	1689:1702	arg1	production					1708:1717	cyanobacterial EPS production	1689:1717	cyanobacterial EPS production	1689:1717	Most importantly, Wzb was able to dephosphorylate Wzc in vitro, suggesting that tyrosine phosphorylation/dephosphorylation plays a role in cyanobacterial EPS production.
30675753	6	2	theme	RPS	1241:1243	arg1	production					1245:1254	RPS production	1241:1254	RPS production	1241:1254	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	5	3	theme	phenotypic	765:774	arg1	changes					776:782	No evident phenotypic changes	754:782	No evident phenotypic changes	754:782	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	1	4	theme	polymeric	210:218	arg1	substances					220:229	extracellular polymeric substances	196:229	extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications	196:362	Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications.
30675753	1	4	theme	polymeric	210:218	arg1	EPS					232:234	EPS	232:234	EPS	232:234	Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications.
30675753	3	5	from	truncation	696:705	arg1	sp					740:741	the unicellular Synechocystis sp	710:741	the unicellular Synechocystis sp	710:741	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	0	6	from	role	4:7	arg1	production					87:96	the production	83:96	the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803	83:166	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	0	7	theme	Wzb	66:68	arg1	role					4:7	The role	0:7	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.	0:167	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	5	8	from	mutants	807:813	arg1	genes					818:822	genes	818:822	genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737)	818:968	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	2	9	theme	pathways	490:497	arg1	differences					507:517	the differences	503:517	the differences between bacterial species	503:543	However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species.
30675753	2	9	theme	pathways	490:497	arg1	understanding					458:470	a poor understanding	451:470	a poor understanding of the production pathways	451:497	However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species.
30675753	7	10	theme	structural	1309:1318	arg1	differences					1320:1330	structural differences	1309:1330	structural differences relative to other phosphatases involved in EPS production	1309:1388	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	0	11	theme	phosphatase	54:64	arg1	Wzb					66:68	the phosphatase Wzb	50:68	the phosphatase Wzb (Slr0328)	50:78	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	0	11	theme	phosphatase	54:64	arg1	Slr0328					71:77	Slr0328	71:77	Slr0328	71:77	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	5	12	theme	evident	757:763	arg1	changes					776:782	No evident phenotypic changes	754:782	No evident phenotypic changes	754:782	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	1	13	theme	biotechnological	334:349	arg1	applications					351:362	biotechnological applications	334:362	biotechnological applications	334:362	Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications.
30675753	2	14	theme	bacterial	527:535	arg1	species					537:543	bacterial species	527:543	bacterial species	527:543	However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species.
30675753	0	15	theme	Synechocystis	145:157	arg1	PCC					159:161	Synechocystis PCC 6803	145:166	Synechocystis PCC 6803	145:166	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	7	16	theme	other	1344:1348	arg1	phosphatases					1350:1361	other phosphatases	1344:1361	other phosphatases involved in EPS production	1344:1388	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	8	17	theme	bacterial	1522:1530	arg1	kinases					1541:1547	bacterial tyrosine kinases	1522:1547	bacterial tyrosine kinases	1522:1547	In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases.
30675753	7	18	theme	EPS	1375:1377	arg1	production					1379:1388	EPS production	1375:1388	EPS production	1375:1388	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	6	19	theme	EPS	1113:1115	arg1	composition					1094:1104	composition	1094:1104	composition	1094:1104	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	6	19	theme	EPS	1113:1115	arg1	EPS					1113:1115	the EPS	1109:1115	the EPS	1109:1115	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	6	19	theme	EPS	1113:1115	arg1	amount					1083:1088	amount	1083:1088	amount	1083:1088	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	5	20	from	copies	846:851	arg1	genome					870:875	Synechocystis genome	856:875	Synechocystis genome	856:875	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	2	21	theme	poor	453:456	arg1	understanding					458:470	a poor understanding	451:470	a poor understanding of the production pathways	451:497	However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species.
30675753	8	22	theme	ATPase	1478:1483	arg1	activities					1500:1509	the ATPase and autokinase activities	1474:1509	the ATPase and autokinase activities typical of bacterial tyrosine kinases	1474:1547	In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases.
30675753	7	23	theme	substrate	1417:1425	arg1	mechanism					1439:1447	a different substrate recognition mechanism	1405:1447	a different substrate recognition mechanism	1405:1447	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	3	24	theme	different	588:596	arg1	pathways					598:605	different pathways	588:605	different pathways of cyanobacterial EPS polymerization, assembly, and export	588:664	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	5	25	theme	multiple	837:844	arg1	∆wzx					902:905	∆wzx (∆sll5049)	902:916	∆wzx (∆sll5049)	902:916	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	5	25	theme	multiple	837:844	arg1	∆wzy					885:888	∆wzy (∆sll0737)	885:899	∆wzy (∆sll0737)	885:899	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	5	25	theme	multiple	837:844	arg1	∆kpsM					919:923	∆kpsM (∆slr2107)	919:934	∆kpsM (∆slr2107)	919:934	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	5	25	theme	multiple	837:844	arg1	∆kpsM∆wzy					941:949	∆kpsM∆wzy (∆slr2107∆sll0737)	941:968	∆kpsM∆wzy (∆slr2107∆sll0737)	941:968	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	5	25	theme	multiple	837:844	arg1	copies					846:851	multiple copies	837:851	multiple copies in Synechocystis genome	837:875	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	5	26	theme	functional	991:1000	arg1	redundancy					1002:1011	functional redundancy	991:1011	functional redundancy	991:1011	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	7	27	theme	relative	1332:1339	arg1	differences					1320:1330	structural differences	1309:1330	structural differences relative to other phosphatases involved in EPS production	1309:1388	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	8	28	theme	autokinase	1489:1498	arg1	activities					1500:1509	the ATPase and autokinase activities	1474:1509	the ATPase and autokinase activities typical of bacterial tyrosine kinases	1474:1547	In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases.
30675753	9	29	theme	tyrosine	1630:1637	arg1	phosphorylation/dephosphorylation					1639:1671	tyrosine phosphorylation/dephosphorylation	1630:1671	tyrosine phosphorylation/dephosphorylation	1630:1671	Most importantly, Wzb was able to dephosphorylate Wzc in vitro, suggesting that tyrosine phosphorylation/dephosphorylation plays a role in cyanobacterial EPS production.
30675753	3	30	theme	related	577:583	arg1	genes					560:564	genes	560:564	genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export	560:664	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	5	31	theme	Synechocystis	856:868	arg1	genome					870:875	Synechocystis genome	856:875	Synechocystis genome	856:875	No evident phenotypic changes were observed for some mutants in genes occurring in multiple copies in Synechocystis genome, namely ∆wzy (∆sll0737), ∆wzx (∆sll5049), ∆kpsM (∆slr2107), and ∆kpsM∆wzy (∆slr2107∆sll0737), strongly suggesting functional redundancy.
30675753	0	32	theme	kinase	25:30	arg1	Sll0923					37:43	Sll0923	37:43	Sll0923	37:43	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	0	32	theme	kinase	25:30	arg1	Wzc					32:34	the tyrosine kinase Wzc	12:34	the tyrosine kinase Wzc (Sll0923)	12:44	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	3	33	theme	cyanobacterial	610:623	arg1	polymerization					629:642	cyanobacterial EPS polymerization	610:642	cyanobacterial EPS polymerization	610:642	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	2	34	theme	biosynthesis/characteristics	407:434	arg1	manipulation/optimization					374:398	manipulation/optimization	374:398	manipulation/optimization of EPS biosynthesis/characteristics	374:434	However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species.
30675753	0	35	theme	tyrosine	16:23	arg1	Sll0923					37:43	Sll0923	37:43	Sll0923	37:43	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	0	35	theme	tyrosine	16:23	arg1	Wzc					32:34	the tyrosine kinase Wzc	12:34	the tyrosine kinase Wzc (Sll0923)	12:44	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	8	36	theme	typical	1511:1517	arg1	activities					1500:1509	the ATPase and autokinase activities	1474:1509	the ATPase and autokinase activities typical of bacterial tyrosine kinases	1474:1547	In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases.
30675753	2	37	theme	production	479:488	arg1	pathways					490:497	the production pathways	475:497	the production pathways	475:497	However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species.
30675753	3	38	theme	EPS	625:627	arg1	polymerization					629:642	cyanobacterial EPS polymerization	610:642	cyanobacterial EPS polymerization	610:642	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	2	39	theme	EPS	403:405	arg1	biosynthesis/characteristics					407:434	EPS biosynthesis/characteristics	403:434	EPS biosynthesis/characteristics	403:434	However, manipulation/optimization of EPS biosynthesis/characteristics is hindered by a poor understanding of the production pathways and the differences between bacterial species.
30675753	0	40	theme	extracellular	101:113	arg1	EPS					137:139	EPS	137:139	EPS	137:139	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	0	40	theme	extracellular	101:113	arg1	substances					125:134	extracellular polymeric substances	101:134	extracellular polymeric substances (EPS)	101:140	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	3	41	theme	export	659:664	arg1	pathways					598:605	different pathways	588:605	different pathways of cyanobacterial EPS polymerization, assembly, and export	588:664	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	6	42	theme	capsular	1174:1181	arg1	production					1160:1169	the production	1156:1169	the production of capsular (CPS) and released (RPS) polysaccharides	1156:1222	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	0	43	theme	Wzc	32:34	arg1	role					4:7	The role	0:7	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.	0:167	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	1	44	theme	unique	283:288	arg1	characteristics					290:304	unique characteristics	283:304	unique characteristics that make them suitable for biotechnological applications	283:362	Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications.
30675753	7	45	theme	different	1407:1415	arg1	mechanism					1439:1447	a different substrate recognition mechanism	1405:1447	a different substrate recognition mechanism	1405:1447	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	6	46	theme	released	1193:1200	arg1	production					1160:1169	the production	1156:1169	the production of capsular (CPS) and released (RPS) polysaccharides	1156:1222	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	7	47	theme	Wzb	1274:1276	arg1	structure					1261:1269	The structure	1257:1269	The structure of Wzb	1257:1276	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	0	48	theme	substances	125:134	arg1	production					87:96	the production	83:96	the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803	83:166	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	3	49	theme	assembly	645:652	arg1	pathways					598:605	different pathways	588:605	different pathways of cyanobacterial EPS polymerization, assembly, and export	588:664	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	1	50	theme	Many	169:172	arg1	cyanobacteria					174:186	Many cyanobacteria	169:186	Many cyanobacteria	169:186	Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications.
30675753	0	51	theme	polymeric	115:123	arg1	EPS					137:139	EPS	137:139	EPS	137:139	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	0	51	theme	polymeric	115:123	arg1	substances					125:134	extracellular polymeric substances	101:134	extracellular polymeric substances (EPS)	101:140	The role of the tyrosine kinase Wzc (Sll0923) and the phosphatase Wzb (Slr0328) in the production of extracellular polymeric substances (EPS) by Synechocystis PCC 6803.
30675753	7	52	theme	recognition	1427:1437	arg1	mechanism					1439:1447	a different substrate recognition mechanism	1405:1447	a different substrate recognition mechanism	1405:1447	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	8	53	theme	tyrosine	1532:1539	arg1	kinases					1541:1547	bacterial tyrosine kinases	1522:1547	bacterial tyrosine kinases	1522:1547	In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases.
30675753	9	54	theme	EPS	1704:1706	arg1	production					1708:1717	cyanobacterial EPS production	1689:1717	cyanobacterial EPS production	1689:1717	Most importantly, Wzb was able to dephosphorylate Wzc in vitro, suggesting that tyrosine phosphorylation/dephosphorylation plays a role in cyanobacterial EPS production.
30675753	7	55	dep	solved	1282:1287	arg1	2.28 Å					1290:1295	2.28 Å	1290:1295	2.28 Å	1290:1295	The structure of Wzb was solved (2.28 Å), revealing structural differences relative to other phosphatases involved in EPS production and suggesting a different substrate recognition mechanism.
30675753	3	56	theme	polymerization	629:642	arg1	pathways					598:605	different pathways	588:605	different pathways of cyanobacterial EPS polymerization, assembly, and export	588:664	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	6	57	dep	capsular	1174:1181	arg1	polysaccharides					1208:1222	polysaccharides	1208:1222	polysaccharides	1208:1222	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	3	58	from	deletion	684:691	arg1	sp					740:741	the unicellular Synechocystis sp	710:741	the unicellular Synechocystis sp	710:741	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	3	59	theme	unicellular	714:724	arg1	sp					740:741	the unicellular Synechocystis sp	710:741	the unicellular Synechocystis sp	710:741	In this work, genes putatively related to different pathways of cyanobacterial EPS polymerization, assembly, and export were targeted for deletion or truncation in the unicellular Synechocystis sp.
30675753	6	60	dep	amount	1083:1088	arg1	the					1079:1081	the	1079:1081	the	1079:1081	In contrast, Δwzc (Δsll0923) and Δwzb (Δslr0328) influenced both the amount and composition of the EPS, establishing that Wzc participates in the production of capsular (CPS) and released (RPS) polysaccharides, and Wzb affects RPS production.
30675753	8	61	theme	kinases	1541:1547	arg1	typical					1511:1517	typical	1511:1517	typical	1511:1517	In addition, Wzc showed the ATPase and autokinase activities typical of bacterial tyrosine kinases.
30675753	1	62	theme	extracellular	196:208	arg1	substances					220:229	extracellular polymeric substances	196:229	extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications	196:362	Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications.
30675753	1	62	theme	extracellular	196:208	arg1	EPS					232:234	EPS	232:234	EPS	232:234	Many cyanobacteria produce extracellular polymeric substances (EPS) mainly composed of heteropolysaccharides with unique characteristics that make them suitable for biotechnological applications.
29997681	6	0	theme	wavenumber	887:896	arg1	region					898:903	the whole wavenumber region	877:903	the whole wavenumber region of all thousands of spectra	877:931	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	11	1	theme	many	2078:2081	arg1	parameters					2089:2098	setting many input parameters	2070:2098	setting many input parameters	2070:2098	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	11	2	theme	endmember	2108:2116	arg1	spectra					2118:2124	the endmember spectra	2104:2124	the endmember spectra	2104:2124	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	2	3	theme	different	282:290	arg1	functions					292:300	different functions	282:300	different functions (e.g. mechanical stability)	282:328	They are optimized for different functions (e.g. mechanical stability) by changing cell form, cell wall thickness and composition.
29997681	4	4	theme	cell	633:636	arg1	wall					638:641	the plant cell wall	623:641	the plant cell wall	623:641	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	9	5	theme	simultaneous	1697:1708	arg1	extraction					1710:1719	a simultaneous extraction	1695:1719	a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS	1695:1807	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	8	6	theme	different	1269:1277	arg1	layers					1289:1294	different cell wall layers	1269:1294	different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness)	1269:1349	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	7	7	theme	curve	1080:1084	arg1	resolution-alternating					1086:1107	multivariate curve resolution-alternating	1067:1107	multivariate curve resolution-alternating	1067:1107	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	2	8	theme	mechanical	308:317	arg1	stability					319:327	mechanical stability	308:327	mechanical stability	308:327	They are optimized for different functions (e.g. mechanical stability) by changing cell form, cell wall thickness and composition.
29997681	13	9	theme	lower	2330:2334	arg1	lack					2336:2339	lower lack	2330:2339	lower lack of fit in the models	2330:2360	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	11	10	theme	setting	2070:2076	arg1	parameters					2089:2098	setting many input parameters	2070:2098	setting many input parameters	2070:2098	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	8	11	theme	wall	1284:1287	arg1	layers					1289:1294	different cell wall layers	1269:1294	different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness)	1269:1349	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	11	12	theme	good	2136:2139	arg1	approximations					2141:2154	good approximations	2136:2154	good approximations of the raw data	2136:2170	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	5	13	theme	multicomponent	669:682	arg1	nature					684:689	the multicomponent nature	665:689	the multicomponent nature of plant cell walls	665:709	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	6	14	theme	spectra	925:931	arg1	thousands					912:920	all thousands	908:920	all thousands of spectra	908:931	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	9	15	theme	components	1737:1746	arg1	extraction					1710:1719	a simultaneous extraction	1695:1719	a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS	1695:1807	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	10	16	dep	closure	1842:1848	arg1	e.g.					1837:1840	e.g.	1837:1840	e.g.	1837:1840	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	7	17	theme	matrix	1042:1047	arg1	factorization					1049:1061	non-negative matrix factorization	1029:1061	non-negative matrix factorization	1029:1061	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	13	18	theme	model	2307:2311	arg1	statistics					2313:2322	the best model statistics	2298:2322	the best model statistics (with lower lack of fit in the models)	2298:2361	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	6	19	theme	thousands	912:920	arg1	region					898:903	the whole wavenumber region	877:903	the whole wavenumber region of all thousands of spectra	877:931	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	8	20	theme	tiny	1307:1310	arg1	S1					1312:1313	tiny S1	1307:1313	tiny S1	1307:1313	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	7	21	theme	multivariate	968:979	arg1	algorithms					990:999	Three multivariate unmixing algorithms	962:999	Three multivariate unmixing algorithms	962:999	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	13	22	theme	inverted	2480:2487	arg1	bands					2489:2493	inverted bands	2480:2493	inverted bands	2480:2493	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	11	23	theme	input	2083:2087	arg1	parameters					2089:2098	setting many input parameters	2070:2098	setting many input parameters	2070:2098	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	2	24	dep	stability	319:327	arg1	e.g.					303:306	e.g.	303:306	e.g.	303:306	They are optimized for different functions (e.g. mechanical stability) by changing cell form, cell wall thickness and composition.
29997681	7	25	theme	component	1009:1017	arg1	analysis					1019:1026	vertex component analysis	1002:1026	vertex component analysis	1002:1026	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	11	26	theme	preliminary	2013:2023	arg1	approach					2025:2032	a good preliminary approach	2006:2032	a good preliminary approach	2006:2032	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	11	26	theme	preliminary	2013:2023	arg1	VCA					1984:1986	CONCLUSIONS VCA	1972:1986	CONCLUSIONS VCA	1972:1986	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	1	27	theme	Plant	128:132	arg1	walls					139:143	BACKGROUND Plant cell walls	117:143	BACKGROUND Plant cell walls	117:143	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	1	27	theme	Plant	128:132	arg1	nanocomposites					149:162	nanocomposites	149:162	nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers	149:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	9	28	dep	i.e.	1581:1584	arg1	performing					1684:1693	performing	1684:1693	performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS	1684:1807	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	9	28	dep	i.e.	1581:1584	arg1	prioritizing					1586:1597	prioritizing	1586:1597	prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA	1586:1679	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	0	29	theme	cell	58:61	arg1	walls					63:67	plant cell walls	52:67	plant cell walls	52:67	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	11	30	dep	fast	2047:2050	arg1	require					2062:2068	require	2062:2068	does not require setting many input parameters	2053:2098	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	0	31	from	approaches	22:31	arg1	images					42:47	Raman images	36:47	Raman images of plant cell walls	36:67	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	5	32	theme	overlapping	727:737	arg1	bands					717:721	many bands	712:721	many bands	712:721	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	5	32	theme	overlapping	727:737	arg1	approaches					770:779	overlapping and classical band integration approaches	727:779	overlapping and classical band integration approaches	727:779	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	5	33	theme	cell	700:703	arg1	walls					705:709	plant cell walls	694:709	plant cell walls	694:709	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	8	34	dep	layers	1289:1294	arg1	including					1297:1305	including	1297:1305	including tiny S1 and S3 with 0.09-0.14 µm thickness	1297:1348	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	3	35	theme	tissues	425:431	arg1	composition					404:414	the composition	400:414	the composition of plant tissues in a non-destructive way	400:456	To reveal the composition of plant tissues in a non-destructive way on the microscale, Raman imaging has become an important tool.
29997681	10	36	from	closure	1842:1848	arg1	VCA					1853:1855	VCA	1853:1855	VCA	1853:1855	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	1	37	from	embedded	196:203	arg1	matrix					210:215	a matrix	208:215	a matrix of polysaccharides and aromatic polymers	208:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	0	38	theme	walls	63:67	arg1	images					42:47	Raman images	36:47	Raman images of plant cell walls	36:67	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	0	39	theme	Multivariate	0:11	arg1	approaches					22:31	Multivariate unmixing approaches	0:31	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?	0:115	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	10	40	theme	principal	1872:1880	arg1	analysis					1892:1899	a previous principal component analysis	1861:1899	a previous principal component analysis filtering step in MCR-ALS	1861:1925	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	11	41	theme	raw	2163:2165	arg1	data					2167:2170	the raw data	2159:2170	the raw data	2159:2170	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	8	42	theme	endmember	1392:1400	arg1	spectra					1402:1408	endmember spectra	1392:1408	endmember spectra with a good signal to noise ratio	1392:1442	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	4	43	theme	spectra	540:546	arg1	Thousands					521:529	Thousands	521:529	Thousands of Raman spectra	521:546	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	8	44	with	S1	1312:1313	arg1	thickness					1340:1348	0.09-0.14 µm thickness	1327:1348	0.09-0.14 µm thickness	1327:1348	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	12	45	theme	endmember	2181:2189	arg1	spectra					2191:2197	Yet the endmember spectra	2173:2197	Yet the endmember spectra	2173:2197	Yet the endmember spectra are more correlated and mixed than those retrieved by NMF and MCR-ALS methods.
29997681	12	45	theme	endmember	2181:2189	arg1	correlated					2208:2217	correlated	2208:2217	correlated	2208:2217	Yet the endmember spectra are more correlated and mixed than those retrieved by NMF and MCR-ALS methods.
29997681	0	46	theme	Raman	36:40	arg1	images					42:47	Raman images	36:47	Raman images of plant cell walls	36:67	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	5	47	theme	classical	743:751	arg1	bands					717:721	many bands	712:721	many bands	712:721	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	5	47	theme	classical	743:751	arg1	approaches					770:779	overlapping and classical band integration approaches	727:779	overlapping and classical band integration approaches	727:779	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	8	48	theme	good	1417:1420	arg1	signal					1422:1427	a good signal	1415:1427	a good signal to noise ratio	1415:1442	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	2	49	theme	cell	342:345	arg1	form					347:350	cell form	342:350	cell form	342:350	They are optimized for different functions (e.g. mechanical stability) by changing cell form, cell wall thickness and composition.
29997681	5	50	theme	integration	758:768	arg1	bands					717:721	many bands	712:721	many bands	712:721	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	5	50	theme	integration	758:768	arg1	approaches					770:779	overlapping and classical band integration approaches	727:779	overlapping and classical band integration approaches	727:779	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	6	51	theme	Multivariate	813:824	arg1	data					826:829	Multivariate data	813:829	Multivariate data analysing approaches	813:850	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	9	52	theme	positive	1617:1624	arg1	endmembers					1626:1635	positive endmembers	1617:1635	positive endmembers	1617:1635	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	9	53	from	variance	1781:1788	arg1	NMF					1793:1795	NMF	1793:1795	NMF	1793:1795	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	9	53	from	variance	1781:1788	arg1	MCR-ALS					1801:1807	MCR-ALS	1801:1807	MCR-ALS	1801:1807	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	0	54	dep	approaches	22:31	arg1	overinterpretation					86:103	overinterpretation	86:103	overinterpretation of results	86:114	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	0	54	dep	approaches	22:31	arg1	insights					74:81	new insights	70:81	new insights	70:81	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	8	55	with	S3	1319:1320	arg1	thickness					1340:1348	0.09-0.14 µm thickness	1327:1348	0.09-0.14 µm thickness	1327:1348	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	2	56	theme	wall	358:361	arg1	thickness					363:371	cell wall thickness	353:371	cell wall thickness	353:371	They are optimized for different functions (e.g. mechanical stability) by changing cell form, cell wall thickness and composition.
29997681	0	57	theme	plant	52:56	arg1	walls					63:67	plant cell walls	52:67	plant cell walls	52:67	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	9	58	theme	orthogonal	1651:1660	arg1	projections					1662:1672	sequential orthogonal projections	1640:1672	sequential orthogonal projections in VCA	1640:1679	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	6	59	dep	potential	864:872	arg1	analysed					936:943	analysed	936:943	is analysed at once	933:951	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	1	60	theme	polymers	249:256	arg1	matrix					210:215	a matrix	208:215	a matrix of polysaccharides and aromatic polymers	208:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	6	61	theme	whole	881:885	arg1	region					898:903	the whole wavenumber region	877:903	the whole wavenumber region of all thousands of spectra	877:931	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	5	62	dep	suitable	791:798	arg1	bands					717:721	many bands	712:721	many bands	712:721	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	5	62	dep	suitable	791:798	arg1	approaches					770:779	overlapping and classical band integration approaches	727:779	overlapping and classical band integration approaches	727:779	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	7	63	theme	squares	1115:1121	arg1	algorithms					990:999	Three multivariate unmixing algorithms	962:999	Three multivariate unmixing algorithms	962:999	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	3	64	theme	important	505:513	arg1	tool					515:518	an important tool	502:518	an important tool	502:518	To reveal the composition of plant tissues in a non-destructive way on the microscale, Raman imaging has become an important tool.
29997681	9	65	theme	Baseline	1455:1462	arg1	correction					1464:1473	Baseline correction	1455:1473	Baseline correction	1455:1473	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	10	66	from	step	1911:1914	arg1	MCR-ALS					1919:1925	MCR-ALS	1919:1925	MCR-ALS	1919:1925	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	6	67	theme	high	859:862	arg1	potential					864:872	a high potential	857:872	a high potential as the whole wavenumber region of all thousands of spectra is analysed at once	857:951	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	4	68	theme	plant	627:631	arg1	wall					638:641	the plant cell wall	623:641	the plant cell wall	623:641	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	7	69	theme	Arabidopsis	1230:1240	arg1	micro-sections					1196:1209	micro-sections	1196:1209	micro-sections of spruce wood and Arabidopsis	1196:1240	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	7	70	theme	multivariate	1067:1078	arg1	resolution-alternating					1086:1107	multivariate curve resolution-alternating	1067:1107	multivariate curve resolution-alternating	1067:1107	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	1	71	theme	cellulose	173:181	arg1	microfibrils					183:194	cellulose microfibrils	173:194	cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers	173:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	4	72	theme	wall	638:641	arg1	one					567:569	one	567:569	one	567:569	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	4	72	theme	wall	638:641	arg1	fingerprint					608:618	a spatially resolved molecular fingerprint	577:618	a spatially resolved molecular fingerprint of the plant cell wall	577:641	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	1	73	theme	embedded	196:203	arg1	microfibrils					183:194	cellulose microfibrils	173:194	cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers	173:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	10	74	theme	Other	1810:1814	arg1	closure					1842:1848	closure	1842:1848	closure	1842:1848	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	10	74	theme	Other	1810:1814	arg1	constraints					1816:1826	Other constraints	1810:1826	Other constraints applied (e.g. closure in VCA)	1810:1856	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	9	75	theme	non-negative	1724:1735	arg1	components					1737:1746	non-negative components	1724:1746	non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS	1724:1807	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	4	76	theme	molecular	598:606	arg1	one					567:569	one	567:569	one	567:569	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	4	76	theme	molecular	598:606	arg1	fingerprint					608:618	a spatially resolved molecular fingerprint	577:618	a spatially resolved molecular fingerprint of the plant cell wall	577:641	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	8	77	with	spectra	1402:1408	arg1	signal					1422:1427	a good signal	1415:1427	a good signal to noise ratio	1415:1442	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	7	78	theme	non-negative	1029:1040	arg1	factorization					1049:1061	non-negative matrix factorization	1029:1061	non-negative matrix factorization	1029:1061	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	13	79	theme	best	2302:2305	arg1	statistics					2313:2322	the best model statistics	2298:2322	the best model statistics (with lower lack of fit in the models)	2298:2361	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	7	80	theme	spruce	1214:1219	arg1	wood					1221:1224	spruce wood	1214:1224	spruce wood	1214:1224	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	10	81	dep	applied	1828:1834	arg1	closure					1842:1848	closure	1842:1848	closure	1842:1848	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	10	81	dep	applied	1828:1834	arg1	constraints					1816:1826	Other constraints	1810:1826	Other constraints applied (e.g. closure in VCA)	1810:1856	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	4	82	dep	acquired	552:559	arg1	one					567:569	one	567:569	one	567:569	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	4	82	dep	acquired	552:559	arg1	fingerprint					608:618	a spatially resolved molecular fingerprint	577:618	a spatially resolved molecular fingerprint of the plant cell wall	577:641	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	11	83	theme	CONCLUSIONS	1972:1982	arg1	approach					2025:2032	a good preliminary approach	2006:2032	a good preliminary approach	2006:2032	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	11	83	theme	CONCLUSIONS	1972:1982	arg1	VCA					1984:1986	CONCLUSIONS VCA	1972:1986	CONCLUSIONS VCA	1972:1986	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	1	84	from	matrix	210:215	arg1	embedded					196:203	embedded	196:203	embedded	196:203	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	9	85	from	projections	1662:1672	arg1	VCA					1677:1679	VCA	1677:1679	VCA	1677:1679	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	7	86	theme	vertex	1002:1007	arg1	analysis					1019:1026	vertex component analysis	1002:1026	vertex component analysis	1002:1026	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	11	87	theme	good	2008:2011	arg1	approach					2025:2032	a good preliminary approach	2006:2032	a good preliminary approach	2006:2032	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	11	87	theme	good	2008:2011	arg1	VCA					1984:1986	CONCLUSIONS VCA	1972:1986	CONCLUSIONS VCA	1972:1986	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	7	88	theme	unmixing	981:988	arg1	algorithms					990:999	Three multivariate unmixing algorithms	962:999	Three multivariate unmixing algorithms	962:999	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	1	89	theme	BACKGROUND	117:126	arg1	walls					139:143	BACKGROUND Plant cell walls	117:143	BACKGROUND Plant cell walls	117:143	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	1	89	theme	BACKGROUND	117:126	arg1	nanocomposites					149:162	nanocomposites	149:162	nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers	149:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	9	90	theme	maximum	1773:1779	arg1	variance					1781:1788	the maximum variance	1769:1788	the maximum variance in NMF and MCR-ALS	1769:1807	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	6	91	contain	have	852:855	arg1	data					826:829	Multivariate data	813:829	Multivariate data analysing approaches	813:850	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	6	91	contain	have	852:855	arg2	potential					864:872	a high potential	857:872	a high potential as the whole wavenumber region of all thousands of spectra is analysed at once	857:951	Multivariate data analysing approaches have a high potential as the whole wavenumber region of all thousands of spectra is analysed at once.
29997681	5	92	theme	many	712:715	arg1	bands					717:721	many bands	712:721	many bands	712:721	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	5	92	theme	many	712:715	arg1	approaches					770:779	overlapping and classical band integration approaches	727:779	overlapping and classical band integration approaches	727:779	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	1	93	theme	cell	134:137	arg1	walls					139:143	BACKGROUND Plant cell walls	117:143	BACKGROUND Plant cell walls	117:143	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	1	93	theme	cell	134:137	arg1	nanocomposites					149:162	nanocomposites	149:162	nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers	149:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	7	94	theme	wood	1221:1224	arg1	micro-sections					1196:1209	micro-sections	1196:1209	micro-sections of spruce wood and Arabidopsis	1196:1240	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	0	95	theme	new	70:72	arg1	insights					74:81	new insights	70:81	new insights	70:81	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	0	96	theme	results	108:114	arg1	overinterpretation					86:103	overinterpretation	86:103	overinterpretation of results	86:114	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	0	96	theme	results	108:114	arg1	insights					74:81	new insights	70:81	new insights	70:81	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	8	97	theme	0.09-0.14 µm	1327:1338	arg1	thickness					1340:1348	0.09-0.14 µm thickness	1327:1348	0.09-0.14 µm thickness	1327:1348	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	5	98	theme	plant	694:698	arg1	walls					705:709	plant cell walls	694:709	plant cell walls	694:709	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	3	99	from	composition	404:414	arg1	way					454:456	a non-destructive way	436:456	a non-destructive way	436:456	To reveal the composition of plant tissues in a non-destructive way on the microscale, Raman imaging has become an important tool.
29997681	5	100	theme	walls	705:709	arg1	nature					684:689	the multicomponent nature	665:689	the multicomponent nature of plant cell walls	665:709	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	8	101	theme	cell	1279:1282	arg1	layers					1289:1294	different cell wall layers	1269:1294	different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness)	1269:1349	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	8	102	theme	cell	1355:1358	arg1	contents					1360:1367	cell contents	1355:1367	cell contents	1355:1367	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	13	103	from	lack	2336:2339	arg1	models					2355:2360	the models	2351:2360	the models	2351:2360	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	0	104	theme	unmixing	13:20	arg1	approaches					22:31	Multivariate unmixing approaches	0:31	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?	0:115	Multivariate unmixing approaches on Raman images of plant cell walls: new insights or overinterpretation of results?
29997681	4	105	theme	Raman	534:538	arg1	spectra					540:546	Raman spectra	534:546	Raman spectra	534:546	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	3	106	theme	plant	419:423	arg1	tissues					425:431	plant tissues	419:431	plant tissues	419:431	To reveal the composition of plant tissues in a non-destructive way on the microscale, Raman imaging has become an important tool.
29997681	13	107	theme	fit	2344:2346	arg1	lack					2336:2339	lower lack	2330:2339	lower lack of fit in the models	2330:2360	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	11	108	theme	data	2167:2170	arg1	approximations					2141:2154	good approximations	2136:2154	good approximations of the raw data	2136:2170	CONCLUSIONS VCA is recommended as a good preliminary approach, since it is fast, does not require setting many input parameters and the endmember spectra result in good approximations of the raw data.
29997681	10	109	theme	component	1882:1890	arg1	analysis					1892:1899	a previous principal component analysis	1861:1899	a previous principal component analysis filtering step in MCR-ALS	1861:1925	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	7	110	dep	RESULTS	954:960	arg1	applied					1128:1134	applied	1128:1134	were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis	1123:1240	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	7	111	theme	purest	1148:1153	arg1	components					1155:1164	the purest components	1144:1164	the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis	1144:1240	RESULTS Three multivariate unmixing algorithms, vertex component analysis, non-negative matrix factorization and multivariate curve resolution-alternating least squares were applied to find the purest components within datasets acquired from micro-sections of spruce wood and Arabidopsis.
29997681	12	112	dep	NMF	2253:2255	arg1	methods					2269:2275	methods	2269:2275	methods	2269:2275	Yet the endmember spectra are more correlated and mixed than those retrieved by NMF and MCR-ALS methods.
29997681	10	113	theme	previous	1863:1870	arg1	analysis					1892:1899	a previous principal component analysis	1861:1899	a previous principal component analysis filtering step in MCR-ALS	1861:1925	Other constraints applied (e.g. closure in VCA) or a previous principal component analysis filtering step in MCR-ALS also contribute to the differences obtained.
29997681	3	114	theme	non-destructive	438:452	arg1	way					454:456	a non-destructive way	436:456	a non-destructive way	436:456	To reveal the composition of plant tissues in a non-destructive way on the microscale, Raman imaging has become an important tool.
29997681	5	115	theme	band	753:756	arg1	bands					717:721	many bands	712:721	many bands	712:721	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	5	115	theme	band	753:756	arg1	approaches					770:779	overlapping and classical band integration approaches	727:779	overlapping and classical band integration approaches	727:779	Nevertheless, due to the multicomponent nature of plant cell walls, many bands are overlapping and classical band integration approaches often not suitable for imaging.
29997681	13	116	theme	artificial	2437:2446	arg1	shapes					2448:2453	artificial shapes	2437:2453	artificial shapes	2437:2453	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	3	117	theme	Raman	477:481	arg1	imaging					483:489	Raman imaging	477:489	Raman imaging	477:489	To reveal the composition of plant tissues in a non-destructive way on the microscale, Raman imaging has become an important tool.
29997681	13	118	with	statistics	2313:2322	arg1	lack					2336:2339	lower lack	2330:2339	lower lack of fit in the models	2330:2360	The latter two give the best model statistics (with lower lack of fit in the models), but care has to be taken about overestimating the rank as it can lead to artificial shapes due to peak splitting or inverted bands.
29997681	9	119	theme	endmembers	1626:1635	arg1	extraction					1603:1612	the extraction	1599:1612	the extraction of positive endmembers by sequential orthogonal projections in VCA	1599:1679	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	1	120	theme	polysaccharides	220:234	arg1	matrix					210:215	a matrix	208:215	a matrix of polysaccharides and aromatic polymers	208:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
29997681	9	121	theme	sequential	1640:1649	arg1	projections					1662:1672	sequential orthogonal projections	1640:1672	sequential orthogonal projections in VCA	1640:1679	Baseline correction influences the results obtained in all methods as well as the way in which algorithm extracts components, i.e. prioritizing the extraction of positive endmembers by sequential orthogonal projections in VCA or performing a simultaneous extraction of non-negative components aiming at explaining the maximum variance in NMF and MCR-ALS.
29997681	4	122	theme	resolved	589:596	arg1	one					567:569	one	567:569	one	567:569	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	4	122	theme	resolved	589:596	arg1	fingerprint					608:618	a spatially resolved molecular fingerprint	577:618	a spatially resolved molecular fingerprint of the plant cell wall	577:641	Thousands of Raman spectra are acquired, each one being a spatially resolved molecular fingerprint of the plant cell wall.
29997681	8	123	theme	noise	1432:1436	arg1	ratio					1438:1442	noise ratio	1432:1442	noise ratio	1432:1442	With all three approaches different cell wall layers (including tiny S1 and S3 with 0.09-0.14 µm thickness) and cell contents were distinguished and endmember spectra with a good signal to noise ratio extracted.
29997681	2	124	theme	cell	353:356	arg1	thickness					363:371	cell wall thickness	353:371	cell wall thickness	353:371	They are optimized for different functions (e.g. mechanical stability) by changing cell form, cell wall thickness and composition.
29997681	1	125	theme	aromatic	240:247	arg1	polymers					249:256	aromatic polymers	240:256	aromatic polymers	240:256	BACKGROUND Plant cell walls are nanocomposites based on cellulose microfibrils embedded in a matrix of polysaccharides and aromatic polymers.
31600785	0	0	theme	mouse	70:74	arg1	model					76:80	mouse model	70:80	mouse model of Peters plus syndrome	70:104	ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.
31600785	2	1	theme	β1-3fucose	427:436	arg1	disaccharide					438:449	an O-linked glucose β1-3fucose disaccharide	407:449	an O-linked glucose β1-3fucose disaccharide	407:449	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	10	2	theme	targets	1897:1903	arg1	subset					1856:1861	a subset	1854:1861	a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20	1854:1920	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	7	3	theme	mouse	1181:1185	arg1	mutants					1194:1200	The mouse B3glct mutants	1177:1200	The mouse B3glct mutants	1177:1200	The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS.
31600785	8	4	theme	white	1331:1335	arg1	spotting					1337:1344	white spotting	1331:1344	white spotting	1331:1344	In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly.
31600785	1	5	theme	β3-glucosyltransferase	293:314	arg1	gene					325:328	the β3-glucosyltransferase (B3GLCT) gene	289:328	the β3-glucosyltransferase (B3GLCT) gene	289:328	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	9	6	theme	reduced	1618:1624	arg1	function					1634:1641	partially reduced ADAMTS9 function	1608:1641	partially reduced ADAMTS9 function	1608:1641	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	6	7	theme	mouse	1158:1162	arg1	development					1164:1174	mouse development	1158:1174	mouse development	1158:1174	Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development.
31600785	1	8	dep	Peters	107:112	arg1	PTRPLS					141:146	PTRPLS	141:146	PTRPLS	141:146	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	1	8	dep	Peters	107:112	arg1	#					133:133	#	133:133	#	133:133	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	5	9	theme	PTRPLS	896:901	arg1	defects					917:923	PTRPLS developmental defects	896:923	PTRPLS developmental defects	896:923	To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles.
31600785	2	10	theme	type	485:488	arg1	TSRs					501:504	TSRs	501:504	TSRs	501:504	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	2	10	theme	type	485:488	arg1	repeats					492:498	properly folded thrombospondin type 1 repeats	454:498	properly folded thrombospondin type 1 repeats (TSRs)	454:505	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	0	11	from	loss	52:55	arg1	model					76:80	mouse model	70:80	mouse model of Peters plus syndrome	70:104	ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.
31600785	4	12	theme	targets	827:833	arg1	subset					817:822	only a subset	810:822	only a subset of targets	810:833	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	5	13	theme	defects	917:923	arg1	origin					886:891	the origin	882:891	the origin of PTRPLS developmental defects	882:923	To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles.
31600785	10	14	theme	compelling	1676:1685	arg1	evidence					1687:1694	compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20	1676:1920	compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20	1676:1920	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	9	15	theme	strong	1385:1390	arg1	evidence					1416:1423	strong genetic and biochemical evidence	1385:1423	strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function	1385:1641	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	2	16	theme	thrombospondin	470:483	arg1	type					485:488	thrombospondin type 1	470:490	properly folded thrombospondin type 1 repeats (TSRs)	454:505	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	1	17	theme	B3GLCT	317:322	arg1	gene					325:328	the β3-glucosyltransferase (B3GLCT) gene	289:328	the β3-glucosyltransferase (B3GLCT) gene	289:328	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	4	18	link	O-linked	655:662	arg1	fucose					664:669	O-linked fucose	655:669	O-linked fucose	655:669	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	9	19	theme	biochemical	1404:1414	arg1	evidence					1416:1423	strong genetic and biochemical evidence	1385:1423	strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function	1385:1641	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	9	20	theme	genetic	1392:1398	arg1	evidence					1416:1423	strong genetic and biochemical evidence	1385:1423	strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function	1385:1641	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	0	21	theme	Peters	85:90	arg1	model					76:80	mouse model	70:80	mouse model of Peters plus syndrome	70:104	ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.
31600785	4	22	theme	POFUT2-modified	713:727	arg1	proteins					729:736	POFUT2-modified proteins	713:736	POFUT2-modified proteins	713:736	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	10	23	theme	sensitive	1873:1881	arg1	targets					1897:1903	highly sensitive POFUT2/B3GLCT targets	1866:1903	highly sensitive POFUT2/B3GLCT targets such as ADAMTS20	1866:1920	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	10	23	theme	sensitive	1873:1881	arg1	ADAMTS20					1913:1920	ADAMTS20	1913:1920	ADAMTS20	1913:1920	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	9	24	dep	evidence	1416:1423	arg1	resulted					1481:1488	resulted	1481:1488	resulted	1481:1488	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	2	25	theme	Protein	331:337	arg1	O-fucosyltransferase					339:358	Protein O-fucosyltransferase 2	331:360	Protein O-fucosyltransferase 2 (POFUT2)	331:369	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	2	25	theme	Protein	331:337	arg1	POFUT2					363:368	POFUT2	363:368	POFUT2	363:368	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	1	26	theme	short	230:234	arg1	stature					236:242	short stature	230:242	short stature	230:242	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	10	27	theme	subset	1856:1861	arg1	disruption					1840:1849	disruption	1840:1849	disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20	1840:1920	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	9	28	from	spotting	1454:1461	arg1	mutants					1473:1479	B3glct mutants	1466:1479	B3glct mutants	1466:1479	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	9	29	theme	partial	1536:1542	arg1	reduction					1544:1552	partial reduction	1536:1552	partial reduction of ADAMTS9 and cleft palate	1536:1580	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	8	30	theme	penetrant	1306:1314	arg1	hydrocephalus					1316:1328	highly penetrant hydrocephalus	1299:1328	highly penetrant hydrocephalus	1299:1328	In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly.
31600785	9	31	theme	white	1448:1452	arg1	spotting					1454:1461	white spotting	1448:1461	white spotting	1448:1461	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	2	32	link	O-linked	410:417	arg1	disaccharide					438:449	an O-linked glucose β1-3fucose disaccharide	407:449	an O-linked glucose β1-3fucose disaccharide	407:449	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	3	33	mod	modified	548:555	arg1	proteins					519:526	Forty-nine proteins	508:526	Forty-nine proteins	508:526	Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily.
31600785	3	33	mod	modified	548:555	arg3	POFUT2					560:565	POFUT2	560:565	POFUT2	560:565	Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily.
31600785	8	34	theme	soft	1350:1353	arg1	tissue					1355:1360	soft tissue	1350:1360	soft tissue	1350:1360	In addition, we observed highly penetrant hydrocephalus, white spotting and soft tissue syndactyly.
31600785	0	35	theme	syndrome	97:104	arg1	model					76:80	mouse model	70:80	mouse model of Peters plus syndrome	70:104	ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.
31600785	3	36	theme	Forty-nine	508:517	arg1	proteins					519:526	Forty-nine proteins	508:526	Forty-nine proteins	508:526	Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily.
31600785	7	37	theme	B3glct	1187:1192	arg1	mutants					1194:1200	The mouse B3glct mutants	1177:1200	The mouse B3glct mutants	1177:1200	The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS.
31600785	2	38	theme	glucose	419:425	arg1	disaccharide					438:449	an O-linked glucose β1-3fucose disaccharide	407:449	an O-linked glucose β1-3fucose disaccharide	407:449	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	7	39	theme	comparable	1252:1261	arg1	abnormalities					1238:1250	craniofacial and skeletal abnormalities	1212:1250	craniofacial and skeletal abnormalities comparable to PTRPLS	1212:1271	The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS.
31600785	5	40	theme	mouse	961:965	arg1	alleles					983:989	two mouse B3glct knockout alleles	957:989	two mouse B3glct knockout alleles	957:989	To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles.
31600785	2	41	theme	O-linked	410:417	arg1	disaccharide					438:449	an O-linked glucose β1-3fucose disaccharide	407:449	an O-linked glucose β1-3fucose disaccharide	407:449	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	0	42	from	B3GLCT	60:65	arg1	model					76:80	mouse model	70:80	mouse model of Peters plus syndrome	70:104	ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.
31600785	5	43	theme	B3glct	967:972	arg1	alleles					983:989	two mouse B3glct knockout alleles	957:989	two mouse B3glct knockout alleles	957:989	To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles.
31600785	1	44	from	defects	167:173	arg1	brachydactyly					248:260	brachydactyly	248:260	brachydactyly	248:260	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	1	44	from	defects	167:173	arg1	hypertelorism					215:227	hypertelorism	215:227	hypertelorism	215:227	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	1	44	from	defects	167:173	arg1	development					182:192	eye development	178:192	eye development	178:192	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	1	44	from	defects	167:173	arg1	forehead					205:212	prominent forehead	195:212	prominent forehead	195:212	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	1	44	from	defects	167:173	arg1	stature					236:242	short stature	230:242	short stature	230:242	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	2	45	theme	folded	463:468	arg1	TSRs					501:504	TSRs	501:504	TSRs	501:504	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	2	45	theme	folded	463:468	arg1	repeats					492:498	properly folded thrombospondin type 1 repeats	454:498	properly folded thrombospondin type 1 repeats (TSRs)	454:505	Protein O-fucosyltransferase 2 (POFUT2) and B3GLCT work sequentially to add an O-linked glucose β1-3fucose disaccharide to properly folded thrombospondin type 1 repeats (TSRs).
31600785	1	46	from	mutations	276:284	arg1	gene					325:328	the β3-glucosyltransferase (B3GLCT) gene	289:328	the β3-glucosyltransferase (B3GLCT) gene	289:328	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	5	47	theme	knockout	974:981	arg1	alleles					983:989	two mouse B3glct knockout alleles	957:989	two mouse B3glct knockout alleles	957:989	To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles.
31600785	10	48	from	defects	1810:1816	arg1	PTRPLS					1821:1826	PTRPLS	1821:1826	PTRPLS	1821:1826	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	4	49	theme	O-linked	655:662	arg1	fucose					664:669	O-linked fucose	655:669	O-linked fucose	655:669	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	10	50	theme	POFUT2/B3GLCT	1883:1895	arg1	targets					1897:1903	highly sensitive POFUT2/B3GLCT targets	1866:1903	highly sensitive POFUT2/B3GLCT targets such as ADAMTS20	1866:1920	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	10	50	theme	POFUT2/B3GLCT	1883:1895	arg1	ADAMTS20					1913:1920	ADAMTS20	1913:1920	ADAMTS20	1913:1920	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	3	51	theme	ADAMTS	603:608	arg1	superfamily					610:620	the ADAMTS superfamily	599:620	the ADAMTS superfamily	599:620	Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily.
31600785	9	52	theme	palate	1575:1580	arg1	reduction					1544:1552	partial reduction	1536:1552	partial reduction of ADAMTS9 and cleft palate	1536:1580	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	9	53	theme	ADAMTS9	1626:1632	arg1	function					1634:1641	partially reduced ADAMTS9 function	1608:1641	partially reduced ADAMTS9 function	1608:1641	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	7	54	theme	skeletal	1229:1236	arg1	abnormalities					1238:1250	craniofacial and skeletal abnormalities	1212:1250	craniofacial and skeletal abnormalities comparable to PTRPLS	1212:1271	The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS.
31600785	9	55	from	reduction	1544:1552	arg1	abnormalities					1517:1529	abnormalities	1517:1529	abnormalities from partial reduction of ADAMTS9 and cleft palate	1517:1580	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	9	56	theme	ADAMTS20	1595:1602	arg1	loss					1587:1590	loss	1587:1590	loss of ADAMTS20	1587:1602	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	9	56	theme	ADAMTS20	1595:1602	arg1	function					1634:1641	partially reduced ADAMTS9 function	1608:1641	partially reduced ADAMTS9 function	1608:1641	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	9	57	theme	cleft	1569:1573	arg1	palate					1575:1580	cleft palate	1569:1580	cleft palate	1569:1580	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	3	58	theme	superfamily	610:620	arg1	members					588:594	members	588:594	members of the ADAMTS superfamily	588:620	Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily.
31600785	3	58	theme	superfamily	610:620	arg1	half					579:582	nearly half	572:582	nearly half	572:582	Forty-nine proteins are predicted to be modified by POFUT2, and nearly half are members of the ADAMTS superfamily.
31600785	9	59	from	hydrocephalus	1430:1442	arg1	mutants					1473:1479	B3glct mutants	1466:1479	B3glct mutants	1466:1479	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	9	60	theme	B3glct	1466:1471	arg1	mutants					1473:1479	B3glct mutants	1466:1479	B3glct mutants	1466:1479	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	6	61	theme	ADAMTS20	1077:1084	arg1	function					1053:1060	function	1053:1060	function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development	1053:1174	Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development.
31600785	1	62	theme	eye	178:180	arg1	development					182:192	eye development	178:192	eye development	178:192	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
31600785	4	63	theme	proteins	729:736	arg1	folding					688:694	folding	688:694	folding	688:694	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	4	63	theme	proteins	729:736	arg1	secretion					700:708	secretion	700:708	secretion	700:708	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	9	64	theme	ADAMTS20	1503:1510	arg1	loss					1495:1498	loss	1495:1498	loss of ADAMTS20	1495:1510	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	5	65	theme	developmental	903:915	arg1	defects					917:923	PTRPLS developmental defects	896:923	PTRPLS developmental defects	896:923	To test this hypothesis and gain insight into the origin of PTRPLS developmental defects, we developed and characterized two mouse B3glct knockout alleles.
31600785	7	66	theme	craniofacial	1212:1223	arg1	abnormalities					1238:1250	craniofacial and skeletal abnormalities	1212:1250	craniofacial and skeletal abnormalities comparable to PTRPLS	1212:1271	The mouse B3glct mutants developed craniofacial and skeletal abnormalities comparable to PTRPLS.
31600785	6	67	theme	ADAMTS9	1065:1071	arg1	function					1053:1060	function	1053:1060	function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development	1053:1174	Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development.
31600785	10	68	theme	B3GLCT	1755:1760	arg1	inactivation					1762:1773	B3GLCT inactivation	1755:1773	B3GLCT inactivation	1755:1773	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	0	69	theme	B3GLCT	60:65	arg1	loss					52:55	loss	52:55	loss of B3GLCT in mouse model of Peters plus syndrome	52:104	ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.
31600785	0	70	from	model	76:80	arg1	loss					52:55	loss	52:55	loss of B3GLCT in mouse model of Peters plus syndrome	52:104	ADAMTS9 and ADAMTS20 are differentially affected by loss of B3GLCT in mouse model of Peters plus syndrome.
31600785	4	71	theme	Previous	623:630	arg1	studies					632:638	Previous studies	623:638	Previous studies	623:638	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	6	72	theme	conserved	1098:1106	arg1	targets					1108:1114	two highly conserved targets	1087:1114	two highly conserved targets whose functions are well characterized in mouse development	1087:1174	Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development.
31600785	6	72	theme	conserved	1098:1106	arg1	ADAMTS9					1065:1071	ADAMTS9	1065:1071	ADAMTS9	1065:1071	Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development.
31600785	9	73	theme	ADAMTS9	1557:1563	arg1	reduction					1544:1552	partial reduction	1536:1552	partial reduction of ADAMTS9 and cleft palate	1536:1580	We provide strong genetic and biochemical evidence that hydrocephalus and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9 and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.
31600785	4	74	theme	B3GLCT-mediated	747:761	arg1	extension					763:771	B3GLCT-mediated extension	747:771	B3GLCT-mediated extension to the disaccharide	747:791	Previous studies suggested that O-linked fucose is essential for folding and secretion of POFUT2-modified proteins and that B3GLCT-mediated extension to the disaccharide is essential for only a subset of targets.
31600785	10	75	theme	developmental	1796:1808	arg1	defects					1810:1816	the developmental defects	1792:1816	the developmental defects in PTRPLS	1792:1826	Combined, these results provide compelling evidence that ADAMTS9 and ADAMTS20 were differentially sensitive to B3GLCT inactivation and suggest that the developmental defects in PTRPLS result from disruption of a subset of highly sensitive POFUT2/B3GLCT targets such as ADAMTS20.
31600785	6	76	theme	B3GLCT	1034:1039	arg1	role					1026:1029	the role	1022:1029	the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development	1022:1174	Using these models, we tested the role of B3GLCT in enabling function of ADAMTS9 and ADAMTS20, two highly conserved targets whose functions are well characterized in mouse development.
31600785	1	77	theme	prominent	195:203	arg1	forehead					205:212	prominent forehead	195:212	prominent forehead	195:212	Peters plus syndrome (MIM #261540 PTRPLS), characterized by defects in eye development, prominent forehead, hypertelorism, short stature and brachydactyly, is caused by mutations in the β3-glucosyltransferase (B3GLCT) gene.
29569918	3	0	theme	tissue	677:682	arg1	section					684:690	the same tissue section	668:690	the same tissue section	668:690	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	5	1	from	differences	946:956	arg1	patterns					972:979	expression patterns	961:979	expression patterns of both sialylated and unsialylated N-glycans	961:1025	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	9	2	from	samples	1604:1610	arg1	analysis					1554:1561	the analysis	1550:1561	the analysis of glycans in clinically relevant tissue samples	1550:1610	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	3	3	link	N-linked	648:655	arg1	glycans					657:663	O- and N-linked glycans	641:663	glycans	657:663	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	2	4	theme	membrane	288:295	arg1	methods					326:332	membrane polysaccharide (CHoMP)-based methods	288:332	membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections	288:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	9	5	theme	chemoenzymatic	1480:1493	arg1	methods					1505:1511	These new chemoenzymatic histology methods	1470:1511	These new chemoenzymatic histology methods	1470:1511	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	2	6	link	N-linked	362:369	arg1	glycans					371:377	O- and N-linked glycans	355:377	glycans	371:377	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	2	7	theme	histology	275:283	arg1	development					245:255	the development	241:255	the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections	241:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	1	8	theme	sensitive	185:193	arg1	tools					195:199	selective and sensitive tools	171:199	selective and sensitive tools for their detection	171:219	Profiling specific glycans in histopathological samples is hampered by the lack of selective and sensitive tools for their detection.
29569918	3	9	gly	sialylated	602:611	arg1	glycans					613:619	unsialylated and sialylated glycans	585:619	unsialylated and sialylated glycans	585:619	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	3	10	gly	unsialylated	585:596	arg1	glycans					613:619	unsialylated and sialylated glycans	585:619	unsialylated and sialylated glycans	585:619	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	3	11	theme	sialylated	602:611	arg1	glycans					613:619	unsialylated and sialylated glycans	585:619	unsialylated and sialylated glycans	585:619	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	3	12	theme	unsialylated	585:596	arg1	glycans					613:619	unsialylated and sialylated glycans	585:619	unsialylated and sialylated glycans	585:619	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	5	13	theme	prostate	905:912	arg1	array					921:925	a prostate cancer array	903:925	a prostate cancer array	903:925	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	3	14	theme	labeling	536:543	arg1	strategies					545:554	tandem labeling and double labeling strategies	509:554	tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively	509:704	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	9	15	theme	glycans	1566:1572	arg1	analysis					1554:1561	the analysis	1550:1561	the analysis of glycans in clinically relevant tissue samples	1550:1610	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	9	16	theme	relevant	1588:1595	arg1	samples					1604:1610	clinically relevant tissue samples	1577:1610	clinically relevant tissue samples	1577:1610	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	8	17	theme	Remarkable	1372:1381	arg1	differences					1383:1393	Remarkable differences	1372:1393	Remarkable differences	1372:1393	Remarkable differences were also detected between adjacent lymph nodes and spleen tissue samples.
29569918	5	18	from	N-glycans	890:898	arg1	array					921:925	a prostate cancer array	903:925	a prostate cancer array	903:925	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	1	19	theme	selective	171:179	arg1	tools					195:199	selective and sensitive tools	171:199	selective and sensitive tools for their detection	171:219	Profiling specific glycans in histopathological samples is hampered by the lack of selective and sensitive tools for their detection.
29569918	1	20	theme	histopathological	118:134	arg1	samples					136:142	histopathological samples	118:142	histopathological samples	118:142	Profiling specific glycans in histopathological samples is hampered by the lack of selective and sensitive tools for their detection.
29569918	7	21	theme	significant	1224:1234	arg1	differences					1236:1246	significant differences	1224:1246	significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes	1224:1369	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	4	22	theme	human	767:771	arg1	arrays					795:800	human multiple-organ cancer arrays	767:800	human multiple-organ cancer arrays	767:800	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	2	23	dep	sialyltransferases	413:430	arg1	sialyltransferases					413:430	sialyltransferases ST3Gal1 and ST6Gal1	413:450	sialyltransferases ST3Gal1 and ST6Gal1	413:450	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	2	23	dep	sialyltransferases	413:430	arg1	ST6Gal1					444:450	ST6Gal1	444:450	ST6Gal1	444:450	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	2	23	dep	sialyltransferases	413:430	arg1	ST3Gal1					432:438	ST3Gal1	432:438	ST3Gal1	432:438	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	0	24	theme	O-Glycans	77:85	arg1	Detection					57:65	the Detection	53:65	the Detection of N- and O-Glycans	53:85	Sialyltransferase-Based Chemoenzymatic Histology for the Detection of N- and O-Glycans.
29569918	8	25	theme	adjacent	1422:1429	arg1	nodes					1437:1441	adjacent lymph nodes	1422:1441	adjacent lymph nodes	1422:1441	Remarkable differences were also detected between adjacent lymph nodes and spleen tissue samples.
29569918	0	26	theme	Sialyltransferase-Based	0:22	arg1	Histology					39:47	Sialyltransferase-Based Chemoenzymatic Histology	0:47	Sialyltransferase-Based Chemoenzymatic Histology for the Detection of N- and O-Glycans.	0:86	Sialyltransferase-Based Chemoenzymatic Histology for the Detection of N- and O-Glycans.
29569918	6	27	theme	Such	1066:1069	arg1	differences					1071:1081	Such differences	1066:1081	Such differences	1066:1081	Such differences were also observed between normal tissue from healthy donors and healthy tissue adjacent to tumors.
29569918	4	28	theme	murine	742:747	arg1	specimens					756:764	murine tissue specimens	742:764	murine tissue specimens	742:764	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	4	29	theme	lymphoma	807:814	arg1	arrays					836:841	lymphoma and prostate cancer arrays	807:841	lymphoma and prostate cancer arrays	807:841	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	5	30	theme	striking	937:944	arg1	differences					946:956	striking differences	937:956	striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples	937:1063	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	7	31	theme	adjacent	1350:1357	arg1	nodes					1365:1369	normal adjacent lymph nodes	1343:1369	normal adjacent lymph nodes	1343:1369	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	3	32	theme	N-linked	648:655	arg1	glycans					657:663	O- and N-linked glycans	641:663	glycans	657:663	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	8	33	theme	spleen	1447:1452	arg1	samples					1461:1467	spleen tissue samples	1447:1467	spleen tissue samples	1447:1467	Remarkable differences were also detected between adjacent lymph nodes and spleen tissue samples.
29569918	9	34	theme	histology	1495:1503	arg1	methods					1505:1511	These new chemoenzymatic histology methods	1470:1511	These new chemoenzymatic histology methods	1470:1511	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	5	35	theme	N-glycans	1017:1025	arg1	patterns					972:979	expression patterns	961:979	expression patterns of both sialylated and unsialylated N-glycans	961:1025	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	3	36	theme	O-	641:642	arg1	glycans					657:663	O- and N-linked glycans	641:663	glycans	657:663	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	4	37	theme	prostate	820:827	arg1	cancer					829:834	prostate cancer	820:834	prostate cancer	820:834	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	5	38	theme	cancerous	1035:1043	arg1	samples					1057:1063	cancerous and healthy samples	1035:1063	cancerous and healthy samples	1035:1063	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	7	39	theme	B-cell	1322:1327	arg1	lymphomas					1329:1337	B-cell lymphomas	1322:1337	B-cell lymphomas	1322:1337	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	3	40	theme	same	672:675	arg1	section					684:690	the same tissue section	668:690	the same tissue section	668:690	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	4	41	theme	cancer	788:793	arg1	arrays					795:800	human multiple-organ cancer arrays	767:800	human multiple-organ cancer arrays	767:800	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	6	42	from	donors	1137:1142	arg1	tissue					1117:1122	normal tissue	1110:1122	normal tissue from healthy donors	1110:1142	Such differences were also observed between normal tissue from healthy donors and healthy tissue adjacent to tumors.
29569918	6	42	from	donors	1137:1142	arg1	tissue					1156:1161	healthy tissue	1148:1161	healthy tissue	1148:1161	Such differences were also observed between normal tissue from healthy donors and healthy tissue adjacent to tumors.
29569918	3	43	theme	double	529:534	arg1	labeling					536:543	double labeling	529:543	double labeling	529:543	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	3	44	theme	tandem	509:514	arg1	labeling					516:523	tandem labeling	509:523	tandem labeling	509:523	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	6	45	theme	normal	1110:1115	arg1	tissue					1117:1122	normal tissue	1110:1122	normal tissue from healthy donors	1110:1142	Such differences were also observed between normal tissue from healthy donors and healthy tissue adjacent to tumors.
29569918	2	46	theme	O-	355:356	arg1	glycans					371:377	O- and N-linked glycans	355:377	glycans	371:377	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	7	47	theme	B-cell	1282:1287	arg1	lymphomas					1300:1308	B-cell and T-cell lymphomas	1282:1308	lymphomas	1300:1308	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	2	48	theme	polysaccharide	297:310	arg1	methods					326:332	membrane polysaccharide (CHoMP)-based methods	288:332	membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections	288:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	9	49	theme	new	1476:1478	arg1	methods					1505:1511	These new chemoenzymatic histology methods	1470:1511	These new chemoenzymatic histology methods	1470:1511	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	2	50	from	detection	342:350	arg1	sections					389:396	tissue sections	382:396	tissue sections	382:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	5	51	theme	tandem	850:855	arg1	labeling					857:864	tandem labeling	850:864	tandem labeling with ST6Gal1	850:877	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	4	52	theme	cancer	829:834	arg1	arrays					836:841	lymphoma and prostate cancer arrays	807:841	lymphoma and prostate cancer arrays	807:841	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	9	53	from	glycans	1566:1572	arg1	samples					1604:1610	clinically relevant tissue samples	1577:1610	clinically relevant tissue samples	1577:1610	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	2	54	theme	-based	319:324	arg1	methods					326:332	membrane polysaccharide (CHoMP)-based methods	288:332	membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections	288:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	1	55	theme	tools	195:199	arg1	lack					163:166	the lack	159:166	the lack of selective and sensitive tools for their detection	159:219	Profiling specific glycans in histopathological samples is hampered by the lack of selective and sensitive tools for their detection.
29569918	9	56	from	analysis	1554:1561	arg1	samples					1604:1610	clinically relevant tissue samples	1577:1610	clinically relevant tissue samples	1577:1610	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	6	57	theme	adjacent	1163:1170	arg1	tissue					1117:1122	normal tissue	1110:1122	normal tissue from healthy donors	1110:1142	Such differences were also observed between normal tissue from healthy donors and healthy tissue adjacent to tumors.
29569918	2	58	theme	CHoMP	313:317	arg1	methods					326:332	membrane polysaccharide (CHoMP)-based methods	288:332	membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections	288:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	9	59	theme	valuable	1531:1538	arg1	tools					1540:1544	valuable tools	1531:1544	valuable tools for the analysis of glycans in clinically relevant tissue samples	1531:1610	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	6	60	theme	healthy	1148:1154	arg1	tissue					1156:1161	healthy tissue	1148:1161	healthy tissue	1148:1161	Such differences were also observed between normal tissue from healthy donors and healthy tissue adjacent to tumors.
29569918	7	61	from	differences	1236:1246	arg1	O-glycans					1264:1272	unsialylated O-glycans	1251:1272	unsialylated O-glycans	1251:1272	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	5	62	theme	healthy	1049:1055	arg1	samples					1057:1063	cancerous and healthy samples	1035:1063	cancerous and healthy samples	1035:1063	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	2	63	theme	chemoenzymatic	260:273	arg1	histology					275:283	chemoenzymatic histology	260:283	chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections	260:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	5	64	theme	cancer	914:919	arg1	array					921:925	a prostate cancer array	903:925	a prostate cancer array	903:925	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	7	65	theme	unsialylated	1251:1262	arg1	O-glycans					1264:1272	unsialylated O-glycans	1251:1272	unsialylated O-glycans	1251:1272	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	3	66	theme	glycans	613:619	arg1	detection					628:636	the detection	624:636	the detection of O- and N-linked glycans	624:663	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	3	66	theme	glycans	613:619	arg1	detection					572:580	the detection	568:580	the detection of unsialylated and sialylated glycans	568:619	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	9	67	theme	tissue	1597:1602	arg1	samples					1604:1610	clinically relevant tissue samples	1577:1610	clinically relevant tissue samples	1577:1610	These new chemoenzymatic histology methods therefore provide valuable tools for the analysis of glycans in clinically relevant tissue samples.
29569918	4	68	theme	tissue	749:754	arg1	specimens					756:764	murine tissue specimens	742:764	murine tissue specimens	742:764	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	2	69	theme	methods	326:332	arg1	histology					275:283	chemoenzymatic histology	260:283	chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections	260:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	7	70	theme	labeling	1194:1201	arg1	technique					1203:1211	Our double labeling technique	1183:1211	Our double labeling technique	1183:1211	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	5	71	theme	expression	961:970	arg1	patterns					972:979	expression patterns	961:979	expression patterns of both sialylated and unsialylated N-glycans	961:1025	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	2	72	theme	tissue	382:387	arg1	sections					389:396	tissue sections	382:396	tissue sections	382:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	0	73	theme	Chemoenzymatic	24:37	arg1	Histology					39:47	Sialyltransferase-Based Chemoenzymatic Histology	0:47	Sialyltransferase-Based Chemoenzymatic Histology for the Detection of N- and O-Glycans.	0:86	Sialyltransferase-Based Chemoenzymatic Histology for the Detection of N- and O-Glycans.
29569918	1	74	theme	specific	98:105	arg1	glycans					107:113	specific glycans	98:113	specific glycans	98:113	Profiling specific glycans in histopathological samples is hampered by the lack of selective and sensitive tools for their detection.
29569918	7	75	theme	lymph	1359:1363	arg1	nodes					1365:1369	normal adjacent lymph nodes	1343:1369	normal adjacent lymph nodes	1343:1369	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	5	76	gly	unsialylated	1004:1015	arg1	N-glycans					1017:1025	both sialylated and unsialylated N-glycans	984:1025	both sialylated and unsialylated N-glycans	984:1025	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	7	77	gly	unsialylated	1251:1262	arg1	O-glycans					1264:1272	unsialylated O-glycans	1251:1272	unsialylated O-glycans	1251:1272	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	2	78	theme	glycans	371:377	arg1	detection					342:350	the detection	338:350	the detection of O- and N-linked glycans on tissue sections	338:396	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	7	79	theme	normal	1343:1348	arg1	nodes					1365:1369	normal adjacent lymph nodes	1343:1369	normal adjacent lymph nodes	1343:1369	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	2	80	theme	sialyltransferases	413:430	arg1	use					406:408	the use	402:408	the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively	402:464	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	8	81	theme	lymph	1431:1435	arg1	nodes					1437:1441	adjacent lymph nodes	1422:1441	adjacent lymph nodes	1422:1441	Remarkable differences were also detected between adjacent lymph nodes and spleen tissue samples.
29569918	2	82	theme	N-linked	362:369	arg1	glycans					371:377	O- and N-linked glycans	355:377	glycans	371:377	Here, we report on the development of chemoenzymatic histology of membrane polysaccharide (CHoMP)-based methods for the detection of O- and N-linked glycans on tissue sections via the use of sialyltransferases ST3Gal1 and ST6Gal1, respectively.
29569918	5	83	theme	unsialylated	1004:1015	arg1	N-glycans					1017:1025	both sialylated and unsialylated N-glycans	984:1025	both sialylated and unsialylated N-glycans	984:1025	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	0	84	theme	N-	70:71	arg1	Detection					57:65	the Detection	53:65	the Detection of N- and O-Glycans	53:85	Sialyltransferase-Based Chemoenzymatic Histology for the Detection of N- and O-Glycans.
29569918	5	85	gly	sialylated	989:998	arg1	N-glycans					1017:1025	both sialylated and unsialylated N-glycans	984:1025	both sialylated and unsialylated N-glycans	984:1025	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	8	86	theme	tissue	1454:1459	arg1	samples					1461:1467	spleen tissue samples	1447:1467	spleen tissue samples	1447:1467	Remarkable differences were also detected between adjacent lymph nodes and spleen tissue samples.
29569918	6	87	theme	healthy	1129:1135	arg1	donors					1137:1142	healthy donors	1129:1142	healthy donors	1129:1142	Such differences were also observed between normal tissue from healthy donors and healthy tissue adjacent to tumors.
29569918	5	88	with	labeling	857:864	arg1	ST6Gal1					871:877	ST6Gal1	871:877	ST6Gal1	871:877	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	3	89	theme	glycans	657:663	arg1	detection					628:636	the detection	624:636	the detection of O- and N-linked glycans	624:663	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	3	89	theme	glycans	657:663	arg1	detection					572:580	the detection	568:580	the detection of unsialylated and sialylated glycans	568:619	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	4	90	theme	multiple-organ	773:786	arg1	arrays					795:800	human multiple-organ cancer arrays	767:800	human multiple-organ cancer arrays	767:800	We applied these methods to screen murine tissue specimens, human multiple-organ cancer arrays, and lymphoma and prostate cancer arrays.
29569918	7	91	theme	T-cell	1293:1298	arg1	lymphomas					1300:1308	B-cell and T-cell lymphomas	1282:1308	lymphomas	1300:1308	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
29569918	5	92	theme	sialylated	989:998	arg1	N-glycans					1017:1025	both sialylated and unsialylated N-glycans	984:1025	both sialylated and unsialylated N-glycans	984:1025	Using tandem labeling with ST6Gal1 to analyze N-glycans in a prostate cancer array, we found striking differences in expression patterns of both sialylated and unsialylated N-glycans between cancerous and healthy samples.
29569918	3	93	theme	labeling	516:523	arg1	strategies					545:554	tandem labeling and double labeling strategies	509:554	tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively	509:704	Combining these two methods, we developed tandem labeling and double labeling strategies that permit the detection of unsialylated and sialylated glycans or the detection of O- and N-linked glycans on the same tissue section, respectively.
29569918	7	94	theme	double	1187:1192	arg1	technique					1203:1211	Our double labeling technique	1183:1211	Our double labeling technique	1183:1211	Our double labeling technique identified significant differences in unsialylated O-glycans between B-cell and T-cell lymphomas and between B-cell lymphomas and normal adjacent lymph nodes.
31656131	6	0	theme	vascular	1024:1031	arg1	muscle					1040:1045	vascular smooth muscle	1024:1045	vascular smooth muscle	1024:1045	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	9	1	theme	proteasome	1787:1796	arg1	system					1798:1803	a nuclear ubiquitin proteasome system	1767:1803	a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression	1767:1857	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	6	2	theme	factor	1181:1186	arg1	A					1188:1188	myocardin-related transcription factor A	1149:1188	myocardin-related transcription factor A	1149:1188	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	6	2	theme	factor	1181:1186	arg1	MRTFA					1142:1146	MRTFA	1142:1146	MRTFA (myocardin-related transcription factor A)	1142:1189	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	1	3	theme	interacting	292:302	arg1	protein					304:310	protein polymerase interacting protein 2	273:312	protein polymerase interacting protein 2	273:312	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	1	3	theme	interacting	292:302	arg1	Poldip2					264:270	The mitochondrial Poldip2	246:270	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2)	236:313	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	9	4	theme	responsible	1805:1815	arg1	system					1798:1803	a nuclear ubiquitin proteasome system	1767:1803	a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression	1767:1857	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	0	5	theme	Ubiquitin	207:215	arg1	System					228:233	a Ubiquitin Proteasome System	205:233	a Ubiquitin Proteasome System	205:233	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	2	6	with	reprograming	432:443	arg1	respiration					474:484	repressed mitochondrial respiration	450:484	repressed mitochondrial respiration	450:484	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	2	6	with	reprograming	432:443	arg1	activity					511:518	increased glycolytic activity	490:518	increased glycolytic activity	490:518	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	9	7	theme	SRF	1821:1823	arg1	stabilization					1825:1837	SRF stabilization	1821:1837	SRF stabilization	1821:1837	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	0	8	theme	System	228:233	arg1	Inhibition					191:200	O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition	131:200	O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System	131:233	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	5	9	theme	metabolic	912:920	arg1	reprograming					922:933	Poldip2-mediated metabolic reprograming	895:933	Poldip2-mediated metabolic reprograming	895:933	OBJECTIVE To determine the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC.
31656131	7	10	theme	platelet-derived	1486:1501	arg1	factor					1510:1515	platelet-derived growth factor	1486:1515	platelet-derived growth factor	1486:1515	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	7	10	theme	platelet-derived	1486:1501	arg1	PDGF					1480:1483	PDGF	1480:1483	PDGF (platelet-derived growth factor)	1480:1516	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	7	11	theme	contractile	1324:1334	arg1	proteins					1336:1343	contractile proteins	1324:1343	contractile proteins	1324:1343	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	5	12	theme	VSMC	963:966	arg1	modulation					949:958	phenotypic modulation	938:958	phenotypic modulation of VSMC	938:966	OBJECTIVE To determine the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC.
31656131	3	13	theme	neointimal	655:664	arg1	hyperplasia					666:676	injury-induced neointimal hyperplasia	640:676	injury-induced neointimal hyperplasia	640:676	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	0	14	dep	Transferase-Dependent	169:189	arg1	GlcNAc					140:145	O-Linked GlcNAc	131:145	O-Linked GlcNAc	131:145	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	8	15	theme	Poldip2	1558:1564	arg1	deficiency					1566:1575	Poldip2 deficiency	1558:1575	Poldip2 deficiency	1558:1575	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	10	16	dep	CONCLUSIONS	1957:1967	arg1	show					1978:1981	show	1978:1981	show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis	1978:2132	CONCLUSIONS Our data show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis.
31656131	0	17	theme	Transferase-Dependent	169:189	arg1	Inhibition					191:200	O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition	131:200	O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System	131:233	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	3	18	attach	linked	688:693	arg2	diseases					679:686	diseases	679:686	diseases linked to loss of vascular smooth muscle differentiation	679:743	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	3	18	attach	linked	688:693	arg1	loss					698:701	loss	698:701	loss of vascular smooth muscle differentiation	698:743	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	6	19	theme	response	1109:1116	arg1	SRF					1098:1100	the SRF	1094:1100	the SRF (serum response factor)	1094:1124	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	6	19	theme	response	1109:1116	arg1	factor					1118:1123	serum response factor	1103:1123	serum response factor	1103:1123	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	7	20	link	platelet-derived	1486:1501	arg1	factor					1510:1515	platelet-derived growth factor	1486:1515	platelet-derived growth factor	1486:1515	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	7	20	link	platelet-derived	1486:1501	arg1	PDGF					1480:1483	PDGF	1480:1483	PDGF (platelet-derived growth factor)	1480:1516	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	5	21	from	role	887:890	arg1	modulation					949:958	phenotypic modulation	938:958	phenotypic modulation of VSMC	938:966	OBJECTIVE To determine the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC.
31656131	10	22	theme	Poldip2	1988:1994	arg1	deficiency					1996:2005	Poldip2 deficiency	1988:2005	Poldip2 deficiency	1988:2005	CONCLUSIONS Our data show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis.
31656131	9	23	theme	phenotype	1919:1927	arg1	establishment					1883:1895	the establishment	1879:1895	the establishment of the differentiated phenotype in Poldip2-deficient cells	1879:1954	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	8	24	theme	hexosamine	1593:1602	arg1	pathway					1617:1623	the hexosamine biosynthetic pathway	1589:1623	the hexosamine biosynthetic pathway	1589:1623	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	1	25	theme	cycle	370:374	arg1	activity					335:342	the activity	331:342	the activity of the tricarboxylic acid cycle	331:374	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	9	26	theme	Poldip2-deficient	1932:1948	arg1	cells					1950:1954	Poldip2-deficient cells	1932:1954	Poldip2-deficient cells	1932:1954	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	0	27	theme	Smooth	89:94	arg1	Muscle					96:101	Vascular Smooth Muscle	80:101	Vascular Smooth Muscle Differentiated Phenotype	80:126	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	2	28	theme	repressed	450:458	arg1	respiration					474:484	repressed mitochondrial respiration	450:484	repressed mitochondrial respiration	450:484	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	2	29	theme	metabolic	422:430	arg1	consequence					382:392	a consequence	380:392	a consequence	380:392	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	2	29	theme	metabolic	422:430	arg1	reprograming					432:443	metabolic reprograming	422:443	metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity	422:518	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	0	30	theme	Differentiated	103:116	arg1	Phenotype					118:126	Vascular Smooth Muscle Differentiated Phenotype	80:126	Vascular Smooth Muscle Differentiated Phenotype	80:126	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	7	31	theme	macrophage-like	1417:1431	arg1	characteristics					1433:1447	macrophage-like characteristics	1417:1447	macrophage-like characteristics	1417:1447	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	2	32	theme	glycolytic	500:509	arg1	activity					511:518	increased glycolytic activity	490:518	increased glycolytic activity	490:518	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	8	33	theme	O-linked	1634:1641	arg1	transferase					1663:1673	O-linked N-acetylglucosamine transferase	1634:1673	O-linked N-acetylglucosamine transferase	1634:1673	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	0	34	theme	Mitochondrial	0:12	arg1	Poldip2					22:28	Mitochondrial Protein Poldip2	0:28	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2)	0:69	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	0	34	theme	Mitochondrial	0:12	arg1	Protein					60:66	Polymerase Delta Interacting Protein 2	31:68	Polymerase Delta Interacting Protein 2	31:68	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	4	35	theme	VSMC	838:841	arg1	differentiation					843:857	VSMC differentiation	838:857	VSMC differentiation	838:857	Thus, we hypothesize that the metabolic reprograming induced by Poldip2 deficiency controls VSMC differentiation.
31656131	2	36	theme	mitochondrial	460:472	arg1	respiration					474:484	repressed mitochondrial respiration	450:484	repressed mitochondrial respiration	450:484	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	9	37	theme	protein	1720:1726	arg1	glycosylation					1728:1740	Increased protein glycosylation	1710:1740	Increased protein glycosylation	1710:1740	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	6	38	theme	myocardin	1127:1135	arg1	expression					1080:1089	the expression	1076:1089	the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A)	1076:1189	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	8	39	theme	-mediated	1675:1683	arg1	O-GlcNAcylation					1693:1707	OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation	1629:1707	OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation	1629:1707	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	3	40	theme	muscle	722:727	arg1	differentiation					729:743	vascular smooth muscle differentiation	706:743	vascular smooth muscle differentiation	706:743	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	0	41	theme	Polymerase	31:40	arg1	Poldip2					22:28	Mitochondrial Protein Poldip2	0:28	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2)	0:69	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	0	41	theme	Polymerase	31:40	arg1	Protein					60:66	Polymerase Delta Interacting Protein 2	31:68	Polymerase Delta Interacting Protein 2	31:68	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	3	42	theme	vascular	706:713	arg1	muscle					722:727	vascular smooth muscle	706:727	vascular smooth muscle differentiation	706:743	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	3	43	theme	Poldip2	551:557	arg1	deletion					539:546	homozygous deletion	528:546	homozygous deletion of Poldip2	528:557	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	0	44	theme	Interacting	48:58	arg1	Poldip2					22:28	Mitochondrial Protein Poldip2	0:28	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2)	0:69	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	0	44	theme	Interacting	48:58	arg1	Protein					60:66	Polymerase Delta Interacting Protein 2	31:68	Polymerase Delta Interacting Protein 2	31:68	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	1	45	theme	tricarboxylic	351:363	arg1	cycle					370:374	the tricarboxylic acid cycle	347:374	the tricarboxylic acid cycle	347:374	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	11	46	theme	mitochondria-initiated	2169:2190	arg1	signaling					2192:2200	mitochondria-initiated signaling	2169:2200	mitochondria-initiated signaling	2169:2200	Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
31656131	1	47	dep	RATIONALE	236:244	arg1	protein					304:310	protein polymerase interacting protein 2	273:312	protein polymerase interacting protein 2	273:312	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	1	47	dep	RATIONALE	236:244	arg1	Poldip2					264:270	The mitochondrial Poldip2	246:270	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2)	236:313	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	1	48	theme	mitochondrial	250:262	arg1	protein					304:310	protein polymerase interacting protein 2	273:312	protein polymerase interacting protein 2	273:312	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	1	48	theme	mitochondrial	250:262	arg1	Poldip2					264:270	The mitochondrial Poldip2	246:270	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2)	236:313	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	9	49	gly	glycosylation	1728:1740	arg1	phenotype					1919:1927	the differentiated phenotype	1900:1927	the differentiated phenotype	1900:1927	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	3	50	theme	heterozygous	570:581	arg1	mice					583:586	heterozygous mice	570:586	heterozygous mice	570:586	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	6	51	theme	smooth	1033:1038	arg1	muscle					1040:1045	vascular smooth muscle	1024:1045	vascular smooth muscle	1024:1045	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	9	52	theme	ubiquitin	1777:1785	arg1	system					1798:1803	a nuclear ubiquitin proteasome system	1767:1803	a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression	1767:1857	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	8	53	link	O-linked	1634:1641	arg1	transferase					1663:1673	O-linked N-acetylglucosamine transferase	1634:1673	O-linked N-acetylglucosamine transferase	1634:1673	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	1	54	theme	polymerase	281:290	arg1	protein					304:310	protein polymerase interacting protein 2	273:312	protein polymerase interacting protein 2	273:312	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	1	54	theme	polymerase	281:290	arg1	Poldip2					264:270	The mitochondrial Poldip2	246:270	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2)	236:313	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	10	55	from	phenotype	2039:2047	arg1	VSMCs					2052:2056	VSMCs	2052:2056	VSMCs	2052:2056	CONCLUSIONS Our data show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis.
31656131	9	56	theme	system	1798:1803	arg1	inhibition					1753:1762	the inhibition	1749:1762	the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression	1749:1857	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	6	57	theme	transcription	1167:1179	arg1	A					1188:1188	myocardin-related transcription factor A	1149:1188	myocardin-related transcription factor A	1149:1188	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	6	57	theme	transcription	1167:1179	arg1	MRTFA					1142:1146	MRTFA	1142:1146	MRTFA (myocardin-related transcription factor A)	1142:1189	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	0	58	theme	Proteasome	217:226	arg1	System					228:233	a Ubiquitin Proteasome System	205:233	a Ubiquitin Proteasome System	205:233	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	6	59	theme	Poldip2	1002:1008	arg1	deficiency					1010:1019	Poldip2 deficiency	1002:1019	Poldip2 deficiency in vascular smooth muscle	1002:1045	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	10	60	theme	proteostasis	2121:2132	arg1	regulation					2092:2101	regulation	2092:2101	regulation of metabolism and proteostasis	2092:2132	CONCLUSIONS Our data show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis.
31656131	11	61	theme	key	2205:2207	arg1	element					2209:2215	key element	2205:2215	key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases	2205:2325	Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
31656131	10	62	theme	metabolism	2106:2115	arg1	regulation					2092:2101	regulation	2092:2101	regulation of metabolism and proteostasis	2092:2132	CONCLUSIONS Our data show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis.
31656131	11	63	theme	programs	2245:2252	arg1	element					2209:2215	key element	2205:2215	key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases	2205:2325	Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
31656131	9	64	theme	KLF4	1843:1846	arg1	repression					1848:1857	KLF4 repression	1843:1857	KLF4 repression	1843:1857	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	0	65	theme	O-Linked	131:138	arg1	GlcNAc					140:145	O-Linked GlcNAc	131:145	O-Linked GlcNAc	131:145	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	11	66	theme	VSMC	2224:2227	arg1	programs					2245:2252	the VSMC differentiation programs	2220:2252	the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases	2220:2325	Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
31656131	5	67	theme	phenotypic	938:947	arg1	modulation					949:958	phenotypic modulation	938:958	phenotypic modulation of VSMC	938:966	OBJECTIVE To determine the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC.
31656131	7	68	theme	growth	1503:1508	arg1	factor					1510:1515	platelet-derived growth factor	1486:1515	platelet-derived growth factor	1486:1515	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	7	68	theme	growth	1503:1508	arg1	PDGF					1480:1483	PDGF	1480:1483	PDGF (platelet-derived growth factor)	1480:1516	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	3	69	theme	injury-induced	640:653	arg1	hyperplasia					666:676	injury-induced neointimal hyperplasia	640:676	injury-induced neointimal hyperplasia	640:676	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	4	70	theme	metabolic	776:784	arg1	reprograming					786:797	the metabolic reprograming	772:797	the metabolic reprograming induced by Poldip2 deficiency	772:827	Thus, we hypothesize that the metabolic reprograming induced by Poldip2 deficiency controls VSMC differentiation.
31656131	8	71	dep	-mediated	1675:1683	arg1	transferase					1663:1673	O-linked N-acetylglucosamine transferase	1634:1673	O-linked N-acetylglucosamine transferase	1634:1673	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	6	72	theme	Krüppel-like	1224:1235	arg1	factor					1237:1242	Krüppel-like factor 4	1224:1244	Krüppel-like factor 4	1224:1244	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	6	72	theme	Krüppel-like	1224:1235	arg1	KLF4					1218:1221	KLF4	1218:1221	KLF4 (Krüppel-like factor 4)	1218:1245	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	9	73	from	establishment	1883:1895	arg1	cells					1950:1954	Poldip2-deficient cells	1932:1954	Poldip2-deficient cells	1932:1954	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	11	74	theme	VSMC	2287:2290	arg1	phenotype					2292:2300	VSMC phenotype	2287:2300	VSMC phenotype	2287:2300	Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
31656131	7	75	theme	high	1309:1312	arg1	levels					1314:1319	high levels	1309:1319	high levels of contractile proteins	1309:1343	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	6	76	theme	serum	1103:1107	arg1	SRF					1098:1100	the SRF	1094:1100	the SRF (serum response factor)	1094:1124	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	6	76	theme	serum	1103:1107	arg1	factor					1118:1123	serum response factor	1103:1123	serum response factor	1103:1123	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	9	77	theme	differentiated	1904:1917	arg1	phenotype					1919:1927	the differentiated phenotype	1900:1927	the differentiated phenotype	1900:1927	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	8	78	theme	biosynthetic	1604:1615	arg1	pathway					1617:1623	the hexosamine biosynthetic pathway	1589:1623	the hexosamine biosynthetic pathway	1589:1623	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	7	79	theme	mouse	1289:1293	arg1	aorta					1295:1299	mouse aorta	1289:1299	mouse aorta	1289:1299	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	0	80	theme	Vascular	80:87	arg1	Muscle					96:101	Vascular Smooth Muscle	80:101	Vascular Smooth Muscle Differentiated Phenotype	80:126	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	1	81	theme	acid	365:368	arg1	cycle					370:374	the tricarboxylic acid cycle	347:374	the tricarboxylic acid cycle	347:374	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	6	82	theme	SRF	1098:1100	arg1	expression					1080:1089	the expression	1076:1089	the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A)	1076:1189	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	0	83	theme	Muscle	96:101	arg1	Phenotype					118:126	Vascular Smooth Muscle Differentiated Phenotype	80:126	Vascular Smooth Muscle Differentiated Phenotype	80:126	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	11	84	theme	differentiation	2229:2243	arg1	programs					2245:2252	the VSMC differentiation programs	2220:2252	the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases	2220:2325	Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
31656131	7	85	theme	Poldip2-deficient	1262:1278	arg1	VSMC					1280:1283	Poldip2-deficient VSMC	1262:1283	Poldip2-deficient VSMC	1262:1283	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	6	86	theme	myocardin-related	1149:1165	arg1	A					1188:1188	myocardin-related transcription factor A	1149:1188	myocardin-related transcription factor A	1149:1188	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	6	86	theme	myocardin-related	1149:1165	arg1	MRTFA					1142:1146	MRTFA	1142:1146	MRTFA (myocardin-related transcription factor A)	1142:1189	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	8	87	theme	N-acetylglucosamine	1643:1661	arg1	transferase					1663:1673	O-linked N-acetylglucosamine transferase	1634:1673	O-linked N-acetylglucosamine transferase	1634:1673	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	5	88	theme	Poldip2-mediated	895:910	arg1	reprograming					922:933	Poldip2-mediated metabolic reprograming	895:933	Poldip2-mediated metabolic reprograming	895:933	OBJECTIVE To determine the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC.
31656131	6	89	theme	MRTFA	1142:1146	arg1	expression					1080:1089	the expression	1076:1089	the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A)	1076:1189	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	2	90	theme	increased	490:498	arg1	activity					511:518	increased glycolytic activity	490:518	increased glycolytic activity	490:518	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	4	91	theme	Poldip2	810:816	arg1	deficiency					818:827	Poldip2 deficiency	810:827	Poldip2 deficiency	810:827	Thus, we hypothesize that the metabolic reprograming induced by Poldip2 deficiency controls VSMC differentiation.
31656131	2	92	theme	Poldip2	395:401	arg1	deficiency					403:412	Poldip2 deficiency	395:412	Poldip2 deficiency	395:412	As a consequence, Poldip2 deficiency induces metabolic reprograming with repressed mitochondrial respiration and increased glycolytic activity.
31656131	5	93	theme	reprograming	922:933	arg1	role					887:890	the role	883:890	the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC	883:966	OBJECTIVE To determine the role of Poldip2-mediated metabolic reprograming in phenotypic modulation of VSMC.
31656131	9	94	theme	Increased	1710:1718	arg1	glycosylation					1728:1740	Increased protein glycosylation	1710:1740	Increased protein glycosylation	1710:1740	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	8	95	theme	protein	1685:1691	arg1	O-GlcNAcylation					1693:1707	OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation	1629:1707	OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation	1629:1707	Regarding the mechanism, we found that Poldip2 deficiency upregulates the hexosamine biosynthetic pathway and OGT (O-linked N-acetylglucosamine transferase)-mediated protein O-GlcNAcylation.
31656131	3	96	theme	smooth	715:720	arg1	muscle					722:727	vascular smooth muscle	706:727	vascular smooth muscle differentiation	706:743	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	3	97	theme	homozygous	528:537	arg1	deletion					539:546	homozygous deletion	528:546	homozygous deletion of Poldip2	528:557	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	0	98	theme	Delta	42:46	arg1	Poldip2					22:28	Mitochondrial Protein Poldip2	0:28	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2)	0:69	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	0	98	theme	Delta	42:46	arg1	Protein					60:66	Polymerase Delta Interacting Protein 2	31:68	Polymerase Delta Interacting Protein 2	31:68	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	6	99	dep	METHODS	969:975	arg1	show					992:995	show	992:995	show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4)	992:1245	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	10	100	theme	differentiated	2024:2037	arg1	phenotype					2039:2047	a highly differentiated phenotype	2015:2047	a highly differentiated phenotype in VSMCs	2015:2056	CONCLUSIONS Our data show that Poldip2 deficiency induces a highly differentiated phenotype in VSMCs through a mechanism that involves regulation of metabolism and proteostasis.
31656131	11	101	theme	vascular	2309:2316	arg1	diseases					2318:2325	vascular diseases	2309:2325	vascular diseases	2309:2325	Additionally, our study positions mitochondria-initiated signaling as key element of the VSMC differentiation programs that can be targeted to modulate VSMC phenotype during vascular diseases.
31656131	3	102	theme	differentiation	729:743	arg1	loss					698:701	loss	698:701	loss of vascular smooth muscle differentiation	698:743	Though homozygous deletion of Poldip2 is lethal, heterozygous mice are viable and show protection against aneurysm and injury-induced neointimal hyperplasia, diseases linked to loss of vascular smooth muscle differentiation.
31656131	9	103	theme	nuclear	1769:1775	arg1	system					1798:1803	a nuclear ubiquitin proteasome system	1767:1803	a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression	1767:1857	Increased protein glycosylation causes the inhibition of a nuclear ubiquitin proteasome system responsible for SRF stabilization and KLF4 repression and is required for the establishment of the differentiated phenotype in Poldip2-deficient cells.
31656131	7	104	theme	proteins	1336:1343	arg1	levels					1314:1319	high levels	1309:1319	high levels of contractile proteins	1309:1343	Consequently, Poldip2-deficient VSMC and mouse aorta express high levels of contractile proteins and, more significantly, these cells do not dedifferentiate nor acquire macrophage-like characteristics when exposed to cholesterol or PDGF (platelet-derived growth factor).
31656131	6	105	from	deficiency	1010:1019	arg1	muscle					1040:1045	vascular smooth muscle	1024:1045	vascular smooth muscle	1024:1045	METHODS AND RESULTS We show that Poldip2 deficiency in vascular smooth muscle in vitro and in vivo induces the expression of the SRF (serum response factor), myocardin, and MRTFA (myocardin-related transcription factor A) and dramatically represses KLF4 (Krüppel-like factor 4).
31656131	0	106	theme	Protein	14:20	arg1	Poldip2					22:28	Mitochondrial Protein Poldip2	0:28	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2)	0:69	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	0	106	theme	Protein	14:20	arg1	Protein					60:66	Polymerase Delta Interacting Protein 2	31:68	Polymerase Delta Interacting Protein 2	31:68	Mitochondrial Protein Poldip2 (Polymerase Delta Interacting Protein 2) Controls Vascular Smooth Muscle Differentiated Phenotype by O-Linked GlcNAc (N-Acetylglucosamine) Transferase-Dependent Inhibition of a Ubiquitin Proteasome System.
31656131	1	107	theme	protein	273:279	arg1	protein					304:310	protein polymerase interacting protein 2	273:312	protein polymerase interacting protein 2	273:312	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
31656131	1	107	theme	protein	273:279	arg1	Poldip2					264:270	The mitochondrial Poldip2	246:270	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2)	236:313	RATIONALE The mitochondrial Poldip2 (protein polymerase interacting protein 2) is required for the activity of the tricarboxylic acid cycle.
29899104	7	0	from	transmissibility	1228:1243	arg1	ducks					1248:1252	ducks	1248:1252	ducks in the absence of mosquitos	1248:1280	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	10	1	theme	E	1767:1767	arg1	protein					1769:1775	the E protein	1763:1775	the E protein	1763:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	10	2	from	acid	1751:1754	arg1	glycosylation					1728:1740	N-linked glycosylation	1719:1740	N-linked glycosylation at amino acid 154 of the E protein	1719:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	10	2	from	acid	1751:1754	arg1	disruption					1705:1714	disruption	1705:1714	disruption of N-linked glycosylation at amino acid 154 of the E protein	1705:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	9	3	theme	envelope	1550:1557	arg1	protein					1559:1565	the envelope protein	1546:1565	the envelope protein of TMUV and its amino acid (S) at position 156	1546:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	9	3	theme	envelope	1550:1557	arg1	responsible					1617:1627	responsible	1617:1627	responsible	1617:1627	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	1	4	theme	encephalitis	230:241	arg1	virus					243:247	Japanese encephalitis virus	221:247	Japanese encephalitis virus	221:247	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	7	5	from	156S	1159:1162	arg1	protein					1180:1186	the envelope protein	1167:1186	the envelope protein	1167:1186	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	4	6	theme	strain	604:609	arg1	FX2010					611:616	The recent TMUV strain FX2010	588:616	The recent TMUV strain FX2010	588:616	The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks.
29899104	1	7	theme	Tembusu	151:157	arg1	virus					159:163	Duck Tembusu virus	146:163	Duck Tembusu virus (TMUV)	146:170	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	7	theme	Tembusu	151:157	arg1	TMUV					166:169	TMUV	166:169	TMUV	166:169	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	11	8	theme	TMUV	1970:1973	arg1	transmission					1975:1986	TMUV transmission	1970:1986	TMUV transmission among ducks	1970:1998	Our findings provide new knowledge about TMUV transmission among ducks.
29899104	10	9	theme	"	1818:1818	arg1	conformation					1793:1804	the conformation	1789:1804	the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks	1789:1926	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	9	10	theme	amino	1583:1587	arg1	S					1595:1595	its amino acid (S)	1579:1596	its amino acid (S) at position 156	1579:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	10	11	theme	150	1810:1812	arg1	loop					1814:1817	loop	1814:1817	loop	1814:1817	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	0	12	theme	Virus	94:98	arg1	Tropism					107:113	Virus Tissue Tropism	94:113	Virus Tissue Tropism	94:113	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	6	13	link	N-linked	933:940	arg1	glycosylation					942:954	N-linked glycosylation	933:954	N-linked glycosylation at amino acid 154 of the E protein	933:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	5	14	theme	envelope	780:787	arg1	protein					789:795	The TMUV envelope protein	771:795	The TMUV envelope protein	771:795	The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility.
29899104	5	14	theme	envelope	780:787	arg1	responsible					819:829	responsible	819:829	responsible	819:829	The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility.
29899104	6	15	theme	domain	898:903	arg1	I					905:905	the domain I	894:905	the domain I	894:905	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	7	16	theme	mosquitos	1272:1280	arg1	absence					1261:1267	the absence	1257:1267	the absence of mosquitos	1257:1280	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	4	17	theme	recent	592:597	arg1	FX2010					611:616	The recent TMUV strain FX2010	588:616	The recent TMUV strain FX2010	588:616	The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks.
29899104	10	18	theme	protein	1829:1835	arg1	"					1818:1818	"150 loop"	1809:1818	"150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks	1809:1926	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	9	19	from	protein	1559:1565	arg1	position					1601:1608	position 156	1601:1612	position 156	1601:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	8	20	theme	ducks.IMPORTANCE	1360:1375	arg1	virus					1385:1389	ducks.IMPORTANCE Tembusu virus	1360:1389	ducks.IMPORTANCE Tembusu virus	1360:1389	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	6	21	theme	mutation	876:883	arg1	S156P					885:889	The mutation S156P	872:889	The mutation S156P in the domain I	872:905	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	3	22	from	replication	515:525	arg1	ducks					581:585	ducks	581:585	ducks	581:585	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	10	23	theme	limited	1852:1858	arg1	replication					1866:1876	limited virus replication	1852:1876	limited virus replication in lungs	1852:1885	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	8	24	theme	similar	1392:1398	arg1	virus					1385:1389	ducks.IMPORTANCE Tembusu virus	1360:1389	ducks.IMPORTANCE Tembusu virus	1360:1389	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	3	25	from	transmissibility	531:546	arg1	ducks					581:585	ducks	581:585	ducks	581:585	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	0	26	theme	Envelope	41:48	arg1	Protein					50:56	the Envelope Protein	37:56	the Envelope Protein of Tembusu Virus	37:73	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	3	27	theme	recent	566:571	arg1	TMUV					573:576	a recent TMUV	564:576	a recent TMUV in ducks	564:585	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	0	28	from	Mutation	9:16	arg1	Protein					50:56	the Envelope Protein	37:56	the Envelope Protein of Tembusu Virus	37:73	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	6	29	theme	N-linked	933:940	arg1	glycosylation					942:954	N-linked glycosylation	933:954	N-linked glycosylation at amino acid 154 of the E protein	933:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	4	30	theme	MM1775	718:723	arg1	replication					690:700	the replication	686:700	the replication of early strain MM1775	686:723	The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks.
29899104	4	30	theme	MM1775	718:723	arg1	limited					729:735	limited	729:735	limited	729:735	The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks.
29899104	0	31	theme	Virus	69:73	arg1	Protein					50:56	the Envelope Protein	37:56	the Envelope Protein of Tembusu Virus	37:73	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	7	32	theme	TMUV	1204:1207	arg1	tropism					1216:1222	TMUV tissue tropism	1204:1222	TMUV tissue tropism	1204:1222	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	10	33	link	N-linked	1719:1726	arg1	glycosylation					1728:1740	N-linked glycosylation	1719:1740	N-linked glycosylation at amino acid 154 of the E protein	1719:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	0	34	from	Position	21:28	arg1	Mutation					9:16	A Single Mutation	0:16	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus	0:73	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	0	34	from	Position	21:28	arg1	Responsible					78:88	Responsible	78:88	Responsible	78:88	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	4	35	theme	early	705:709	arg1	MM1775					718:723	early strain MM1775	705:723	early strain MM1775	705:723	The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks.
29899104	1	36	theme	West	250:253	arg1	virus					260:264	West Nile virus	250:264	West Nile virus	250:264	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	9	37	from	transmission	1652:1663	arg1	ducks					1668:1672	ducks	1668:1672	ducks	1668:1672	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	10	38	from	disruption	1705:1714	arg1	acid					1751:1754	amino acid 154	1745:1758	amino acid 154	1745:1758	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	6	39	theme	E	981:981	arg1	protein					983:989	the E protein	977:989	the E protein	977:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	10	40	theme	glycosylation	1728:1740	arg1	disruption					1705:1714	disruption	1705:1714	disruption of N-linked glycosylation at amino acid 154 of the E protein	1705:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	9	41	from	tropism	1640:1646	arg1	ducks					1668:1672	ducks	1668:1672	ducks	1668:1672	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	6	42	from	S156P	885:889	arg1	I					905:905	the domain I	894:905	the domain I	894:905	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	8	43	theme	novel	1304:1308	arg1	insights					1310:1317	novel insights	1304:1317	novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors	1304:1523	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	6	44	gly	glycosylation	942:954	arg1	protein					983:989	the E protein	977:989	the E protein	977:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	6	44	gly	glycosylation	942:954	arg1	acid					965:968	amino acid 154	959:972	amino acid 154	959:972	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	6	44	gly	glycosylation	942:954	arg2	acid					965:968	amino acid 154	959:972	amino acid 154	959:972	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	1	45	theme	other	178:182	arg1	flaviviruses					199:210	other mosquito-borne flaviviruses	178:210	other mosquito-borne flaviviruses	178:210	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	45	theme	other	178:182	arg1	virus					243:247	Japanese encephalitis virus	221:247	Japanese encephalitis virus	221:247	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	45	theme	other	178:182	arg1	virus					278:282	Bagaza virus	271:282	Bagaza virus	271:282	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	45	theme	other	178:182	arg1	virus					260:264	West Nile virus	250:264	West Nile virus	250:264	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	6	46	theme	"	1032:1032	arg1	conformation					1007:1018	the conformation	1003:1018	the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks	1003:1127	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	0	47	from	Tropism	107:113	arg1	Ducks					139:143	Ducks	139:143	Ducks	139:143	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	10	48	theme	amino	1745:1749	arg1	acid					1751:1754	amino acid 154	1745:1758	amino acid 154	1745:1758	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	8	49	theme	TMUV	1336:1339	arg1	transmission					1341:1352	TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors	1336:1523	TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors	1336:1523	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	5	50	theme	domain	805:810	arg1	I					812:812	its domain I	801:812	its domain I	801:812	The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility.
29899104	6	51	theme	150	1024:1026	arg1	loop					1028:1031	loop	1028:1031	loop	1028:1031	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	10	52	theme	protein	1769:1775	arg1	glycosylation					1728:1740	N-linked glycosylation	1719:1740	N-linked glycosylation at amino acid 154 of the E protein	1719:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	3	53	theme	molecular	449:457	arg1	basis					459:463	the key molecular basis	441:463	the key molecular basis of flavivirus transmissibility	441:494	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	8	54	theme	other	1403:1407	arg1	flaviviruses					1424:1435	other mosquito-borne flaviviruses	1403:1435	other mosquito-borne flaviviruses such as WNV, JEV, and BAGV	1403:1462	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	8	54	theme	other	1403:1407	arg1	WNV					1445:1447	WNV	1445:1447	WNV	1445:1447	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	8	54	theme	other	1403:1407	arg1	BAGV					1459:1462	BAGV	1459:1462	BAGV	1459:1462	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	8	54	theme	other	1403:1407	arg1	JEV					1450:1452	JEV	1450:1452	JEV	1450:1452	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	8	55	theme	vectors	1517:1523	arg1	presence					1496:1503	the presence	1492:1503	the presence of mosquito vectors	1492:1523	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	1	56	theme	Japanese	221:228	arg1	virus					243:247	Japanese encephalitis virus	221:247	Japanese encephalitis virus	221:247	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	11	57	theme	new	1950:1952	arg1	knowledge					1954:1962	new knowledge	1950:1962	new knowledge about TMUV transmission among ducks	1950:1998	Our findings provide new knowledge about TMUV transmission among ducks.
29899104	0	58	from	Transmissibility	119:134	arg1	Ducks					139:143	Ducks	139:143	Ducks	139:143	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	6	59	theme	E	1041:1041	arg1	protein					1043:1049	the E protein	1037:1049	the E protein	1037:1049	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	3	60	theme	transmissibility	479:494	arg1	basis					459:463	the key molecular basis	441:463	the key molecular basis of flavivirus transmissibility	441:494	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	1	61	theme	Duck	146:149	arg1	virus					159:163	Duck Tembusu virus	146:163	Duck Tembusu virus (TMUV)	146:170	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	61	theme	Duck	146:149	arg1	TMUV					166:169	TMUV	166:169	TMUV	166:169	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	9	62	theme	TMUV	1570:1573	arg1	protein					1559:1565	the envelope protein	1546:1565	the envelope protein of TMUV and its amino acid (S) at position 156	1546:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	9	62	theme	TMUV	1570:1573	arg1	responsible					1617:1627	responsible	1617:1627	responsible	1617:1627	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	6	63	theme	virus	1066:1070	arg1	replication					1072:1082	virus replication	1066:1082	virus replication	1066:1082	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	4	64	theme	TMUV	599:602	arg1	FX2010					611:616	The recent TMUV strain FX2010	588:616	The recent TMUV strain FX2010	588:616	The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks.
29899104	10	65	theme	loop	1814:1817	arg1	"					1818:1818	"150 loop"	1809:1818	"150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks	1809:1926	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	0	66	theme	Tissue	100:105	arg1	Tropism					107:113	Virus Tissue Tropism	94:113	Virus Tissue Tropism	94:113	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	3	67	theme	virus	509:513	arg1	replication					515:525	virus replication	509:525	virus replication	509:525	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	10	68	gly	glycosylation	1728:1740	arg1	protein					1769:1775	the E protein	1763:1775	the E protein	1763:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	10	68	gly	glycosylation	1728:1740	arg1	acid					1751:1754	amino acid 154	1745:1758	amino acid 154	1745:1758	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	10	68	gly	glycosylation	1728:1740	arg2	acid					1751:1754	amino acid 154	1745:1758	amino acid 154	1745:1758	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	9	69	theme	acid	1589:1592	arg1	S					1595:1595	its amino acid (S)	1579:1596	its amino acid (S) at position 156	1579:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	6	70	theme	protein	1043:1049	arg1	"					1032:1032	"150 loop"	1023:1032	"150 loop"	1023:1032	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	3	71	theme	early	554:558	arg1	replication					515:525	virus replication	509:525	virus replication	509:525	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	3	71	theme	early	554:558	arg1	TMUV					573:576	a recent TMUV	564:576	a recent TMUV in ducks	564:585	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	3	71	theme	early	554:558	arg1	transmissibility					531:546	transmissibility	531:546	transmissibility	531:546	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	9	72	theme	S	1595:1595	arg1	protein					1559:1565	the envelope protein	1546:1565	the envelope protein of TMUV and its amino acid (S) at position 156	1546:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	9	72	theme	S	1595:1595	arg1	responsible					1617:1627	responsible	1617:1627	responsible	1617:1627	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	8	73	theme	Tembusu	1377:1383	arg1	virus					1385:1389	ducks.IMPORTANCE Tembusu virus	1360:1389	ducks.IMPORTANCE Tembusu virus	1360:1389	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	10	74	theme	E	1827:1827	arg1	protein					1829:1835	the E protein	1823:1835	the E protein	1823:1835	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	9	75	from	position	1601:1608	arg1	TMUV					1570:1573	TMUV	1570:1573	TMUV	1570:1573	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	9	75	from	position	1601:1608	arg1	protein					1559:1565	the envelope protein	1546:1565	the envelope protein of TMUV and its amino acid (S) at position 156	1546:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	9	75	from	position	1601:1608	arg1	S					1595:1595	its amino acid (S)	1579:1596	its amino acid (S) at position 156	1579:1612	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	9	75	from	position	1601:1608	arg1	responsible					1617:1627	responsible	1617:1627	responsible	1617:1627	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	5	76	theme	TMUV	775:778	arg1	protein					789:795	The TMUV envelope protein	771:795	The TMUV envelope protein	771:795	The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility.
29899104	5	76	theme	TMUV	775:778	arg1	responsible					819:829	responsible	819:829	responsible	819:829	The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility.
29899104	6	77	theme	amino	959:963	arg1	acid					965:968	amino acid 154	959:972	amino acid 154	959:972	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	8	78	theme	mosquito-borne	1409:1422	arg1	flaviviruses					1424:1435	other mosquito-borne flaviviruses	1403:1435	other mosquito-borne flaviviruses such as WNV, JEV, and BAGV	1403:1462	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	8	78	theme	mosquito-borne	1409:1422	arg1	WNV					1445:1447	WNV	1445:1447	WNV	1445:1447	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	8	78	theme	mosquito-borne	1409:1422	arg1	BAGV					1459:1462	BAGV	1459:1462	BAGV	1459:1462	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	8	78	theme	mosquito-borne	1409:1422	arg1	JEV					1450:1452	JEV	1450:1452	JEV	1450:1452	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	0	79	theme	Tembusu	61:67	arg1	Virus					69:73	Tembusu Virus	61:73	Tembusu Virus	61:73	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	5	80	theme	tissue	835:840	arg1	tropism					842:848	tissue tropism	835:848	tissue tropism	835:848	The TMUV envelope protein and its domain I were responsible for tissue tropism and transmissibility.
29899104	6	81	theme	glycosylation	942:954	arg1	disruption					919:928	disruption	919:928	disruption of N-linked glycosylation at amino acid 154 of the E protein	919:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	9	82	theme	tissue	1633:1638	arg1	tropism					1640:1646	tissue tropism	1633:1646	tissue tropism	1633:1646	We demonstrate that the envelope protein of TMUV and its amino acid (S) at position 156 is responsible for tissue tropism and transmission in ducks.
29899104	6	83	from	acid	965:968	arg1	disruption					919:928	disruption	919:928	disruption of N-linked glycosylation at amino acid 154 of the E protein	919:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	6	83	from	acid	965:968	arg1	glycosylation					942:954	N-linked glycosylation	933:954	N-linked glycosylation at amino acid 154 of the E protein	933:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	4	84	theme	strain	711:716	arg1	MM1775					718:723	early strain MM1775	705:723	early strain MM1775	705:723	The recent TMUV strain FX2010 replicated systemically and transmitted efficiently in ducks, while the replication of early strain MM1775 was limited and did not transmit among ducks.
29899104	10	85	theme	virus	1860:1864	arg1	replication					1866:1876	limited virus replication	1852:1876	limited virus replication in lungs	1852:1885	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	7	86	from	ducks	1248:1252	arg1	absence					1261:1267	the absence	1257:1267	the absence of mosquitos	1257:1280	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	6	87	from	disruption	919:928	arg1	acid					965:968	amino acid 154	959:972	amino acid 154	959:972	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	3	88	from	TMUV	573:576	arg1	ducks					581:585	ducks	581:585	ducks	581:585	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	0	89	theme	Single	2:7	arg1	Mutation					9:16	A Single Mutation	0:16	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus	0:73	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	0	89	theme	Single	2:7	arg1	Responsible					78:88	Responsible	78:88	Responsible	78:88	A Single Mutation at Position 156 in the Envelope Protein of Tembusu Virus Is Responsible for Virus Tissue Tropism and Transmissibility in Ducks.
29899104	7	90	theme	tissue	1209:1214	arg1	tropism					1216:1222	TMUV tissue tropism	1204:1222	TMUV tissue tropism	1204:1222	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	2	91	theme	mosquito	386:393	arg1	vectors					395:401	mosquito vectors	386:401	mosquito vectors	386:401	To date, why these flaviviruses can be transmitted without mosquito vectors remains poorly understood.
29899104	10	92	theme	mutation	1679:1686	arg1	S156P					1688:1692	The mutation S156P	1675:1692	The mutation S156P	1675:1692	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	6	93	theme	protein	983:989	arg1	glycosylation					942:954	N-linked glycosylation	933:954	N-linked glycosylation at amino acid 154 of the E protein	933:989	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	1	94	theme	Nile	255:258	arg1	virus					260:264	West Nile virus	250:264	West Nile virus	250:264	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	10	95	theme	N-linked	1719:1726	arg1	glycosylation					1728:1740	N-linked glycosylation	1719:1740	N-linked glycosylation at amino acid 154 of the E protein	1719:1775	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	10	96	from	replication	1866:1876	arg1	lungs					1881:1885	lungs	1881:1885	lungs	1881:1885	The mutation S156P results in disruption of N-linked glycosylation at amino acid 154 of the E protein and changes the conformation of "150 loop" of the E protein, which induces limited virus replication in lungs and abrogates transmission between ducks.
29899104	7	97	theme	envelope	1171:1178	arg1	protein					1180:1186	the envelope protein	1167:1186	the envelope protein	1167:1186	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	3	98	theme	key	445:447	arg1	basis					459:463	the key molecular basis	441:463	the key molecular basis of flavivirus transmissibility	441:494	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
29899104	1	99	theme	Bagaza	271:276	arg1	virus					278:282	Bagaza virus	271:282	Bagaza virus	271:282	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	100	theme	mosquito-borne	184:197	arg1	flaviviruses					199:210	other mosquito-borne flaviviruses	178:210	other mosquito-borne flaviviruses	178:210	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	100	theme	mosquito-borne	184:197	arg1	virus					243:247	Japanese encephalitis virus	221:247	Japanese encephalitis virus	221:247	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	100	theme	mosquito-borne	184:197	arg1	virus					278:282	Bagaza virus	271:282	Bagaza virus	271:282	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	1	100	theme	mosquito-borne	184:197	arg1	virus					260:264	West Nile virus	250:264	West Nile virus	250:264	Duck Tembusu virus (TMUV), like other mosquito-borne flaviviruses, such as Japanese encephalitis virus, West Nile virus, and Bagaza virus, is able to transmit vector-independently.
29899104	7	101	from	tropism	1216:1222	arg1	ducks					1248:1252	ducks	1248:1252	ducks in the absence of mosquitos	1248:1280	These data indicate that the 156S in the envelope protein is critical for TMUV tissue tropism and transmissibility in ducks in the absence of mosquitos.
29899104	6	102	theme	loop	1028:1031	arg1	"					1032:1032	"150 loop"	1023:1032	"150 loop"	1023:1032	The mutation S156P in the domain I resulted in disruption of N-linked glycosylation at amino acid 154 of the E protein and changed the conformation of "150 loop" of the E protein, which reduced virus replication in lungs and abrogated transmission in ducks.
29899104	8	103	theme	mosquito	1508:1515	arg1	vectors					1517:1523	mosquito vectors	1508:1523	mosquito vectors	1508:1523	Our findings provide novel insights on understanding TMUV transmission among ducks.IMPORTANCE Tembusu virus, similar to other mosquito-borne flaviviruses such as WNV, JEV, and BAGV, can be transmitted without the presence of mosquito vectors.
29899104	3	104	theme	flavivirus	468:477	arg1	transmissibility					479:494	flavivirus transmissibility	468:494	flavivirus transmissibility	468:494	To explore the key molecular basis of flavivirus transmissibility, we compared virus replication and transmissibility of an early and a recent TMUV in ducks.
30368301	14	0	theme	chains	2141:2146	arg1	presence					2122:2129	the presence	2118:2129	the presence of glycan chains	2118:2146	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	6	1	from	proportion	1115:1124	arg1	different					1091:1099	different	1091:1099	different	1091:1099	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	4	2	dep	isoforms	670:677	arg1	Ovitrelle®					703:712	Ovitrelle®	703:712	Ovitrelle® (recombinant r-hCG)	703:732	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	2	dep	isoforms	670:677	arg1	r-hCG					727:731	recombinant r-hCG	715:731	recombinant r-hCG	715:731	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	2	dep	isoforms	670:677	arg1	Pregnyl					738:744	Pregnyl	738:744	Pregnyl (hCG isolated from the urine of pregnant women, u-hCG)	738:799	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	2	dep	isoforms	670:677	arg1	isoforms					670:677	the isoforms	666:677	the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG)	666:799	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	16	3	theme	ionized	2531:2537	arg1	isoforms					2546:2553	the ionized intact isoforms	2527:2553	the ionized intact isoforms	2527:2553	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	4	4	theme	Gel	619:621	arg1	CGE					640:642	CGE	640:642	CGE	640:642	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	4	theme	Gel	619:621	arg1	Electrophoresis					623:637	Capillary Gel Electrophoresis	609:637	Capillary Gel Electrophoresis (CGE)	609:643	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	14	5	theme	detection	1967:1975	arg1	strategies					1977:1986	Two detection strategies	1963:1986	Two detection strategies	1963:1986	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	13	6	theme	quadrupole	1928:1937	arg1	spectrometer					1949:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	14	7	theme	m/z	2187:2189	arg1	1000-2000					2199:2207	1000-2000	2199:2207	1000-2000	2199:2207	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	14	7	theme	m/z	2187:2189	arg1	values					2191:2196	the higher m/z values	2176:2196	the higher m/z values (1000-2000)	2176:2208	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	4	8	theme	pregnant	778:785	arg1	women					787:791	pregnant women	778:791	pregnant women	778:791	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	16	9	theme	isoforms	2546:2553	arg1	state					2518:2522	the charge state	2507:2522	the charge state of the ionized intact isoforms	2507:2553	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	16	9	theme	isoforms	2546:2553	arg1	ratio					2579:2583	the signal-to-noise ratio	2559:2583	the signal-to-noise ratio	2559:2583	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	3	10	theme	other	521:525	arg1	modifications					546:558	other post-translational modifications	521:558	other post-translational modifications	521:558	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	1	11	theme	human	191:195	arg1	Gonadotropin					207:218	the human Chorionic Gonadotropin	187:218	the human Chorionic Gonadotropin (hCG) hormone	187:232	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	1	11	theme	human	191:195	arg1	hCG					221:223	hCG	221:223	hCG	221:223	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	6	12	theme	peak	1021:1024	arg1	intensities					1026:1036	peak intensities	1021:1036	peak intensities	1021:1036	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	8	13	theme	isoforms	1227:1234	arg1	ranges					1209:1214	The pI ranges	1202:1214	The pI ranges of the hCG isoforms	1202:1234	The pI ranges of the hCG isoforms were found between 3.4 and 4.7, and 4.5 and 5.2 for r-hCG and u-hCG, respectively.
30368301	16	14	theme	signal-to-noise	2563:2577	arg1	ratio					2579:2583	the signal-to-noise ratio	2559:2583	the signal-to-noise ratio	2559:2583	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	10	15	theme	modifier	1565:1572	arg1	pH					1444:1445	The pH	1440:1445	The pH	1440:1445	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	15	theme	modifier	1565:1572	arg1	nature					1452:1457	the nature	1448:1457	the nature	1448:1457	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	15	theme	modifier	1565:1572	arg1	content					1542:1548	the content	1538:1548	the content	1538:1548	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	15	theme	modifier	1565:1572	arg1	concentration					1468:1480	the concentration	1464:1480	the concentration of the background electrolyte	1464:1510	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	15	theme	modifier	1565:1572	arg1	nature					1527:1532	nature	1527:1532	nature	1527:1532	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	1	16	theme	Gonadotropin	207:218	arg1	hormone					226:232	the human Chorionic Gonadotropin (hCG) hormone	187:232	the human Chorionic Gonadotropin (hCG) hormone	187:232	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	1	17	from	level	248:252	arg1	Electrophoresis					168:182	Capillary Electrophoresis	158:182	Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level	158:252	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	12	18	theme	different	1750:1758	arg1	isoforms					1764:1771	different hCG isoforms	1750:1771	different hCG isoforms	1750:1771	The final CZE-UV method allowed distinguishing at least 6 peaks, corresponding to different hCG isoforms.
30368301	11	19	theme	coated	1603:1608	arg1	capillary					1610:1618	a coated capillary	1601:1618	a coated capillary	1601:1618	The use of a coated capillary to avoid protein adsorption was also evaluated.
30368301	6	20	from	different	1091:1099	arg1	proportion					1115:1124	proportion	1115:1124	proportion	1115:1124	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	6	20	from	different	1091:1099	arg1	nature					1104:1109	nature	1104:1109	nature	1104:1109	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	13	21	theme	electrospray	1885:1896	arg1	source					1909:1914	an electrospray ionization source	1882:1914	an electrospray ionization source	1882:1914	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	10	22	theme	organic	1557:1563	arg1	modifier					1565:1572	its organic modifier	1553:1572	its organic modifier	1553:1572	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	17	23	theme	hCG-based	2631:2639	arg1	drugs					2641:2645	the two hCG-based drugs	2623:2645	the two hCG-based drugs	2623:2645	The final method was used to compare the two hCG-based drugs, demonstrating the potential of the developed CZE-MS method for isoforms fingerprinting.
30368301	0	24	from	level	99:103	arg1	electrophoresis					37:51	capillary electrophoresis	27:51	capillary electrophoresis of human Chorionic Gonadotropin at the intact level	27:103	First characterizations by capillary electrophoresis of human Chorionic Gonadotropin at the intact level.
30368301	16	25	theme	charge	2511:2516	arg1	state					2518:2522	the charge state	2507:2522	the charge state of the ionized intact isoforms	2507:2553	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	2	26	theme	so-called	379:387	arg1	subunit					370:376	a β subunit	366:376	a β subunit	366:376	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	2	26	theme	so-called	379:387	arg1	hCGα					389:392	so-called hCGα	379:392	so-called hCGα	379:392	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	6	27	from	nature	1104:1109	arg1	different					1091:1099	different	1091:1099	different	1091:1099	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	4	28	attach	isolated	751:758	arg2	hCG					747:749	hCG	747:749	hCG isolated from the urine of pregnant women	747:791	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	28	attach	isolated	751:758	arg2	u-hCG					794:798	u-hCG	794:798	u-hCG	794:798	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	28	attach	isolated	751:758	arg1	urine					769:773	the urine	765:773	the urine of pregnant women	765:791	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	0	29	theme	Gonadotropin	72:83	arg1	electrophoresis					37:51	capillary electrophoresis	27:51	capillary electrophoresis of human Chorionic Gonadotropin at the intact level	27:103	First characterizations by capillary electrophoresis of human Chorionic Gonadotropin at the intact level.
30368301	9	30	used	used	1348:1351	arg2	information					1324:1334	This information	1319:1334	This information	1319:1334	This information was further used to develop the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE).
30368301	6	31	theme	Different	906:914	arg1	profiles					920:927	Different CGE profiles	906:927	Different CGE profiles	906:927	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	8	32	theme	pI	1206:1207	arg1	ranges					1209:1214	The pI ranges	1202:1214	The pI ranges of the hCG isoforms	1202:1234	The pI ranges of the hCG isoforms were found between 3.4 and 4.7, and 4.5 and 5.2 for r-hCG and u-hCG, respectively.
30368301	1	33	theme	Capillary	158:166	arg1	Electrophoresis					168:182	Capillary Electrophoresis	158:182	Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level	158:252	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	17	34	theme	CZE-MS	2693:2698	arg1	method					2700:2705	the developed CZE-MS method	2679:2705	the developed CZE-MS method	2679:2705	The final method was used to compare the two hCG-based drugs, demonstrating the potential of the developed CZE-MS method for isoforms fingerprinting.
30368301	10	35	dep	nature	1527:1532	arg1	the					1523:1525	the	1523:1525	the	1523:1525	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	4	36	theme	recombinant	715:725	arg1	Ovitrelle®					703:712	Ovitrelle®	703:712	Ovitrelle® (recombinant r-hCG)	703:732	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	36	theme	recombinant	715:725	arg1	r-hCG					727:731	recombinant r-hCG	715:731	recombinant r-hCG	715:731	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	12	37	theme	CZE-UV	1678:1683	arg1	method					1685:1690	The final CZE-UV method	1668:1690	The final CZE-UV method	1668:1690	The final CZE-UV method allowed distinguishing at least 6 peaks, corresponding to different hCG isoforms.
30368301	5	38	theme	large	878:882	arg1	heterogeneity					884:896	the large heterogeneity	874:896	the large heterogeneity of hCG	874:903	As expected, CGE led to a better resolution than SDS-PAGE and confirmed the large heterogeneity of hCG.
30368301	9	39	theme	Capillary	1402:1410	arg1	CZE					1434:1436	CZE	1434:1436	CZE	1434:1436	This information was further used to develop the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE).
30368301	9	39	theme	Capillary	1402:1410	arg1	Electrophoresis					1417:1431	Capillary Zone Electrophoresis	1402:1431	Capillary Zone Electrophoresis (CZE)	1402:1437	This information was further used to develop the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE).
30368301	6	40	theme	hCG-based	955:963	arg1	drugs					965:969	the two hCG-based drugs	947:969	the two hCG-based drugs	947:969	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	17	41	used	used	2607:2610	arg2	method					2596:2601	The final method	2586:2601	The final method	2586:2601	The final method was used to compare the two hCG-based drugs, demonstrating the potential of the developed CZE-MS method for isoforms fingerprinting.
30368301	4	42	theme	drugs	696:700	arg1	Ovitrelle®					703:712	Ovitrelle®	703:712	Ovitrelle® (recombinant r-hCG)	703:732	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	42	theme	drugs	696:700	arg1	Pregnyl					738:744	Pregnyl	738:744	Pregnyl (hCG isolated from the urine of pregnant women, u-hCG)	738:799	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	42	theme	drugs	696:700	arg1	isoforms					670:677	the isoforms	666:677	the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG)	666:799	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	14	43	theme	m/z	2025:2027	arg1	100-1000					2037:2044	100-1000	2037:2044	100-1000	2037:2044	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	14	43	theme	m/z	2025:2027	arg1	values					2029:2034	the lower m/z values	2015:2034	the lower m/z values (100-1000)	2015:2045	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	10	44	theme	background	1489:1498	arg1	electrolyte					1500:1510	the background electrolyte	1485:1510	the background electrolyte	1485:1510	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	16	45	dep	composition	2359:2369	arg1	The					2355:2357	The	2355:2357	The	2355:2357	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	14	46	theme	sugar	2073:2077	arg1	residues					2079:2086	some sugar residues	2068:2086	some sugar residues	2068:2086	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	14	46	theme	sugar	2073:2077	arg1	ions					2102:2105	diagnostic ions	2091:2105	diagnostic ions	2091:2105	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	7	47	theme	Focusing	1185:1192	arg1	IsoElectrophoretic					1166:1183	Capillary IsoElectrophoretic Focusing	1156:1192	Capillary IsoElectrophoretic Focusing (CIEF)	1156:1199	This result was confirmed by Capillary IsoElectrophoretic Focusing (CIEF).
30368301	7	47	theme	Focusing	1185:1192	arg1	CIEF					1195:1198	CIEF	1195:1198	CIEF	1195:1198	This result was confirmed by Capillary IsoElectrophoretic Focusing (CIEF).
30368301	6	48	contain	contain	1073:1079	arg1	drugs					1067:1071	the drugs	1063:1071	the drugs	1063:1071	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	6	48	contain	contain	1073:1079	arg2	isoforms					1081:1088	isoforms	1081:1088	isoforms	1081:1088	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	13	49	theme	information	1812:1822	arg1	level					1803:1807	the level	1799:1807	the level of information obtained	1799:1831	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	2	50	theme	human	326:330	arg1	pregnancy					332:340	the human pregnancy	322:340	the human pregnancy	322:340	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	0	51	theme	human	56:60	arg1	Gonadotropin					72:83	human Chorionic Gonadotropin	56:83	human Chorionic Gonadotropin	56:83	First characterizations by capillary electrophoresis of human Chorionic Gonadotropin at the intact level.
30368301	14	52	theme	intact	2249:2254	arg1	isoforms					2264:2271	the multiple charged intact protein isoforms	2228:2271	the multiple charged intact protein isoforms	2228:2271	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	7	53	theme	Capillary	1156:1164	arg1	IsoElectrophoretic					1166:1183	Capillary IsoElectrophoretic Focusing	1156:1192	Capillary IsoElectrophoretic Focusing (CIEF)	1156:1199	This result was confirmed by Capillary IsoElectrophoretic Focusing (CIEF).
30368301	7	53	theme	Capillary	1156:1164	arg1	CIEF					1195:1198	CIEF	1195:1198	CIEF	1195:1198	This result was confirmed by Capillary IsoElectrophoretic Focusing (CIEF).
30368301	11	54	theme	protein	1629:1635	arg1	adsorption					1637:1646	protein adsorption	1629:1646	protein adsorption	1629:1646	The use of a coated capillary to avoid protein adsorption was also evaluated.
30368301	15	55	theme	voltage	2324:2330	arg1	values					2332:2337	the fragmentor and capillary voltage values	2295:2337	the fragmentor and capillary voltage values	2295:2337	For both approaches, the fragmentor and capillary voltage values were optimized.
30368301	13	56	theme	mass	1944:1947	arg1	spectrometer					1949:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	14	57	theme	multiple	2232:2239	arg1	isoforms					2264:2271	the multiple charged intact protein isoforms	2228:2271	the multiple charged intact protein isoforms	2228:2271	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	2	58	gly	glycoprotein	296:307	arg1	hCG					272:274	hCG	272:274	hCG	272:274	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	2	58	gly	glycoprotein	296:307	arg1	glycoprotein					296:307	a hetero-dimeric glycoprotein	279:307	a hetero-dimeric glycoprotein	279:307	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	16	59	theme	higher	2463:2468	arg1	values					2474:2479	the higher m/z values	2459:2479	the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio	2459:2583	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	17	60	theme	final	2590:2594	arg1	method					2596:2601	The final method	2586:2601	The final method	2586:2601	The final method was used to compare the two hCG-based drugs, demonstrating the potential of the developed CZE-MS method for isoforms fingerprinting.
30368301	16	61	theme	liquid	2403:2408	arg1	composition					2359:2369	composition	2359:2369	composition	2359:2369	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	16	61	theme	liquid	2403:2408	arg1	flow-rate					2379:2387	the flow-rate	2375:2387	the flow-rate	2375:2387	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	1	62	theme	intact	241:246	arg1	level					248:252	the intact level	237:252	the intact level	237:252	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	4	63	theme	women	787:791	arg1	urine					769:773	the urine	765:773	the urine of pregnant women	765:791	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	14	64	theme	glycan	2134:2139	arg1	chains					2141:2146	glycan chains	2134:2146	glycan chains	2134:2146	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	3	65	theme	isoforms	486:493	arg1	glycoforms					506:515	glycoforms	506:515	glycoforms	506:515	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	3	65	theme	isoforms	486:493	arg1	number					476:481	a high number	469:481	a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize	469:599	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	3	65	theme	isoforms	486:493	arg1	modifications					546:558	other post-translational modifications	521:558	other post-translational modifications	521:558	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	13	66	theme	TQ	1940:1941	arg1	spectrometer					1949:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	3	67	theme	glycosylation	438:450	arg1	sites					452:456	8 potential glycosylation sites	426:456	8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize	426:599	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	4	68	dep	Pregnyl	738:744	arg1	hCG					747:749	hCG	747:749	hCG isolated from the urine of pregnant women	747:791	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	68	dep	Pregnyl	738:744	arg1	u-hCG					794:798	u-hCG	794:798	u-hCG	794:798	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	69	theme	Capillary	609:617	arg1	CGE					640:642	CGE	640:642	CGE	640:642	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	69	theme	Capillary	609:617	arg1	Electrophoresis					623:637	Capillary Gel Electrophoresis	609:637	Capillary Gel Electrophoresis (CGE)	609:643	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	12	70	theme	hCG	1760:1762	arg1	isoforms					1764:1771	different hCG isoforms	1750:1771	different hCG isoforms	1750:1771	The final CZE-UV method allowed distinguishing at least 6 peaks, corresponding to different hCG isoforms.
30368301	6	71	theme	intensities	1026:1036	arg1	number					983:988	number	983:988	number of peaks, migration times, and peak intensities	983:1036	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	2	72	theme	hetero-dimeric	281:294	arg1	hCG					272:274	hCG	272:274	hCG	272:274	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	2	72	theme	hetero-dimeric	281:294	arg1	glycoprotein					296:307	a hetero-dimeric glycoprotein	279:307	a hetero-dimeric glycoprotein	279:307	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	1	73	theme	Chorionic	197:205	arg1	Gonadotropin					207:218	the human Chorionic Gonadotropin	187:218	the human Chorionic Gonadotropin (hCG) hormone	187:232	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	1	73	theme	Chorionic	197:205	arg1	hCG					221:223	hCG	221:223	hCG	221:223	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	16	74	theme	intact	2539:2544	arg1	isoforms					2546:2553	the ionized intact isoforms	2527:2553	the ionized intact isoforms	2527:2553	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	6	75	theme	times	1010:1014	arg1	number					983:988	number	983:988	number of peaks, migration times, and peak intensities	983:1036	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	3	76	contain	has	422:424	arg2	sites					452:456	8 potential glycosylation sites	426:456	8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize	426:599	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	3	76	contain	has	422:424	arg1	hCG					418:420	hCG	418:420	hCG	418:420	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	13	77	theme	triple	1921:1926	arg1	spectrometer					1949:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	a triple quadrupole (TQ) mass spectrometer	1919:1960	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	3	78	theme	post-translational	527:544	arg1	modifications					546:558	other post-translational modifications	521:558	other post-translational modifications	521:558	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	1	79	theme	present	113:119	arg1	work					121:124	the present work	109:124	the present work	109:124	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	6	80	theme	different	1091:1099	arg1	isoforms					1081:1088	isoforms	1081:1088	isoforms	1081:1088	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	14	81	theme	diagnostic	2091:2100	arg1	residues					2079:2086	some sugar residues	2068:2086	some sugar residues	2068:2086	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	14	81	theme	diagnostic	2091:2100	arg1	ions					2102:2105	diagnostic ions	2091:2105	diagnostic ions	2091:2105	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	11	82	theme	capillary	1610:1618	arg1	use					1594:1596	The use	1590:1596	The use of a coated capillary to avoid protein adsorption	1590:1646	The use of a coated capillary to avoid protein adsorption was also evaluated.
30368301	17	83	theme	developed	2683:2691	arg1	method					2700:2705	the developed CZE-MS method	2679:2705	the developed CZE-MS method	2679:2705	The final method was used to compare the two hCG-based drugs, demonstrating the potential of the developed CZE-MS method for isoforms fingerprinting.
30368301	13	84	theme	ionization	1898:1907	arg1	source					1909:1914	an electrospray ionization source	1882:1914	an electrospray ionization source	1882:1914	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	17	85	theme	method	2700:2705	arg1	potential					2666:2674	the potential	2662:2674	the potential of the developed CZE-MS method for isoforms fingerprinting	2662:2733	The final method was used to compare the two hCG-based drugs, demonstrating the potential of the developed CZE-MS method for isoforms fingerprinting.
30368301	1	86	theme	first	131:135	arg1	characterizations					137:153	the first characterizations	127:153	the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level	127:252	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	6	87	theme	CGE	916:918	arg1	profiles					920:927	Different CGE profiles	906:927	Different CGE profiles	906:927	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	0	88	theme	intact	92:97	arg1	level					99:103	the intact level	88:103	the intact level	88:103	First characterizations by capillary electrophoresis of human Chorionic Gonadotropin at the intact level.
30368301	2	89	theme	specific	310:317	arg1	hCG					272:274	hCG	272:274	hCG	272:274	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	2	89	theme	specific	310:317	arg1	glycoprotein					296:307	a hetero-dimeric glycoprotein	279:307	a hetero-dimeric glycoprotein	279:307	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	10	90	theme	electrolyte	1500:1510	arg1	pH					1444:1445	The pH	1440:1445	The pH	1440:1445	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	90	theme	electrolyte	1500:1510	arg1	nature					1452:1457	the nature	1448:1457	the nature	1448:1457	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	90	theme	electrolyte	1500:1510	arg1	content					1542:1548	the content	1538:1548	the content	1538:1548	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	90	theme	electrolyte	1500:1510	arg1	concentration					1468:1480	the concentration	1464:1480	the concentration of the background electrolyte	1464:1510	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	10	90	theme	electrolyte	1500:1510	arg1	nature					1527:1532	nature	1527:1532	nature	1527:1532	The pH, the nature, and the concentration of the background electrolyte as well as the nature and the content of its organic modifier were optimized.
30368301	13	91	theme	CZE	1838:1840	arg1	instrument					1842:1851	the CZE instrument	1834:1851	the CZE instrument	1834:1851	To significantly improve the level of information obtained, the CZE instrument was then coupled by means of an electrospray ionization source to a triple quadrupole (TQ) mass spectrometer.
30368301	9	92	theme	hCG	1386:1388	arg1	isoforms					1390:1397	the hCG isoforms	1382:1397	the hCG isoforms	1382:1397	This information was further used to develop the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE).
30368301	17	93	theme	isoforms	2711:2718	arg1	fingerprinting					2720:2733	isoforms fingerprinting	2711:2733	isoforms fingerprinting	2711:2733	The final method was used to compare the two hCG-based drugs, demonstrating the potential of the developed CZE-MS method for isoforms fingerprinting.
30368301	4	94	used	used	649:652	arg2	CGE					640:642	CGE	640:642	CGE	640:642	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	4	94	used	used	649:652	arg2	Electrophoresis					623:637	Capillary Gel Electrophoresis	609:637	Capillary Gel Electrophoresis (CGE)	609:643	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	5	95	theme	better	828:833	arg1	resolution					835:844	a better resolution	826:844	a better resolution than SDS-PAGE	826:858	As expected, CGE led to a better resolution than SDS-PAGE and confirmed the large heterogeneity of hCG.
30368301	3	96	gly	glycosylation	438:450	arg2	8					426:426	8	426:426	8	426:426	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	3	96	gly	glycosylation	438:450	arg2	sites					452:456	8 potential glycosylation sites	426:456	8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize	426:599	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	0	97	theme	capillary	27:35	arg1	electrophoresis					37:51	capillary electrophoresis	27:51	capillary electrophoresis of human Chorionic Gonadotropin at the intact level	27:103	First characterizations by capillary electrophoresis of human Chorionic Gonadotropin at the intact level.
30368301	9	98	theme	Zone	1412:1415	arg1	CZE					1434:1436	CZE	1434:1436	CZE	1434:1436	This information was further used to develop the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE).
30368301	9	98	theme	Zone	1412:1415	arg1	Electrophoresis					1417:1431	Capillary Zone Electrophoresis	1402:1431	Capillary Zone Electrophoresis (CZE)	1402:1437	This information was further used to develop the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE).
30368301	8	99	theme	hCG	1223:1225	arg1	isoforms					1227:1234	the hCG isoforms	1219:1234	the hCG isoforms	1219:1234	The pI ranges of the hCG isoforms were found between 3.4 and 4.7, and 4.5 and 5.2 for r-hCG and u-hCG, respectively.
30368301	4	100	theme	hCG-based	686:694	arg1	drugs					696:700	two hCG-based drugs	682:700	two hCG-based drugs	682:700	First, Capillary Gel Electrophoresis (CGE) was used to separate the isoforms of two hCG-based drugs: Ovitrelle® (recombinant r-hCG) and Pregnyl (hCG isolated from the urine of pregnant women, u-hCG).
30368301	14	101	theme	lower	2019:2023	arg1	100-1000					2037:2044	100-1000	2037:2044	100-1000	2037:2044	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	14	101	theme	lower	2019:2023	arg1	values					2029:2034	the lower m/z values	2015:2034	the lower m/z values (100-1000)	2015:2045	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	12	102	theme	final	1672:1676	arg1	method					1685:1690	The final CZE-UV method	1668:1690	The final CZE-UV method	1668:1690	The final CZE-UV method allowed distinguishing at least 6 peaks, corresponding to different hCG isoforms.
30368301	16	103	theme	m/z	2470:2472	arg1	values					2474:2479	the higher m/z values	2459:2479	the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio	2459:2583	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	5	104	gly	heterogeneity	884:896	arg1	hCG					901:903	hCG	901:903	hCG	901:903	As expected, CGE led to a better resolution than SDS-PAGE and confirmed the large heterogeneity of hCG.
30368301	14	105	theme	higher	2180:2185	arg1	1000-2000					2199:2207	1000-2000	2199:2207	1000-2000	2199:2207	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	14	105	theme	higher	2180:2185	arg1	values					2191:2196	the higher m/z values	2176:2196	the higher m/z values (1000-2000)	2176:2208	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	2	106	theme	β	368:368	arg1	hCGβ					398:401	hCGβ	398:401	hCGβ	398:401	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	2	106	theme	β	368:368	arg1	subunit					370:376	a β subunit	366:376	a β subunit	366:376	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	2	106	theme	β	368:368	arg1	hCGα					389:392	so-called hCGα	379:392	so-called hCGα	379:392	hCG is a hetero-dimeric glycoprotein, specific to the human pregnancy, consisting of an α and a β subunit, so-called hCGα and hCGβ, respectively.
30368301	0	107	theme	Chorionic	62:70	arg1	Gonadotropin					72:83	human Chorionic Gonadotropin	56:83	human Chorionic Gonadotropin	56:83	First characterizations by capillary electrophoresis of human Chorionic Gonadotropin at the intact level.
30368301	14	108	theme	protein	2256:2262	arg1	isoforms					2264:2271	the multiple charged intact protein isoforms	2228:2271	the multiple charged intact protein isoforms	2228:2271	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	16	109	dep	increase	2498:2505	arg1	both					2493:2496	both	2493:2496	both	2493:2496	The composition and the flow-rate of the sheath liquid were then optimized for the strategy focusing on the higher m/z values in order to both increase the charge state of the ionized intact isoforms and the signal-to-noise ratio.
30368301	15	110	theme	capillary	2314:2322	arg1	values					2332:2337	the fragmentor and capillary voltage values	2295:2337	the fragmentor and capillary voltage values	2295:2337	For both approaches, the fragmentor and capillary voltage values were optimized.
30368301	14	111	theme	charged	2241:2247	arg1	isoforms					2264:2271	the multiple charged intact protein isoforms	2228:2271	the multiple charged intact protein isoforms	2228:2271	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	6	112	theme	migration	1000:1008	arg1	times					1010:1014	migration times	1000:1014	migration times	1000:1014	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	9	113	theme	isoforms	1390:1397	arg1	separation					1368:1377	the separation	1364:1377	the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE)	1364:1437	This information was further used to develop the separation of the hCG isoforms by Capillary Zone Electrophoresis (CZE).
30368301	3	114	theme	potential	428:436	arg1	sites					452:456	8 potential glycosylation sites	426:456	8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize	426:599	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	15	115	theme	fragmentor	2299:2308	arg1	values					2332:2337	the fragmentor and capillary voltage values	2295:2337	the fragmentor and capillary voltage values	2295:2337	For both approaches, the fragmentor and capillary voltage values were optimized.
30368301	1	116	theme	hormone	226:232	arg1	Electrophoresis					168:182	Capillary Electrophoresis	158:182	Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level	158:252	In the present work, the first characterizations by Capillary Electrophoresis of the human Chorionic Gonadotropin (hCG) hormone at the intact level were carried out.
30368301	5	117	theme	hCG	901:903	arg1	heterogeneity					884:896	the large heterogeneity	874:896	the large heterogeneity of hCG	874:903	As expected, CGE led to a better resolution than SDS-PAGE and confirmed the large heterogeneity of hCG.
30368301	6	118	theme	peaks	993:997	arg1	number					983:988	number	983:988	number of peaks, migration times, and peak intensities	983:1036	Different CGE profiles were obtained for the two hCG-based drugs, varying in number of peaks, migration times, and peak intensities, thus demonstrating that the drugs contain isoforms, different in nature and proportion.
30368301	14	119	dep	identify	2059:2066	arg1	to					2056:2057	to	2056:2057	to	2056:2057	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
30368301	3	120	theme	high	471:474	arg1	glycoforms					506:515	glycoforms	506:515	glycoforms	506:515	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	3	120	theme	high	471:474	arg1	number					476:481	a high number	469:481	a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize	469:599	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	3	120	theme	high	471:474	arg1	modifications					546:558	other post-translational modifications	521:558	other post-translational modifications	521:558	hCG has 8 potential glycosylation sites leading to a high number of isoforms (including glycoforms and other post-translational modifications) that we are interesting to characterize.
30368301	14	121	used	used	1993:1996	arg2	strategies					1977:1986	Two detection strategies	1963:1986	Two detection strategies	1963:1986	Two detection strategies were used, one focusing on the lower m/z values (100-1000) in order to identify some sugar residues as diagnostic ions to confirm the presence of glycan chains, and the second focusing on the higher m/z values (1000-2000), corresponding to the multiple charged intact protein isoforms.
34917767	4	0	theme	ionization	885:894	arg1	spectrometry					901:912	nanospray ionization mass spectrometry	875:912	nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition	875:975	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	7	1	with	%	1173:1173	arg1	interference					1190:1201	no matrix interference	1180:1201	no matrix interference	1180:1201	Recovery of synthetic GSLs spiked into plasma was 99-104% with no matrix interference.
34917767	3	2	theme	n = 19	703:708	arg1	individuals					711:721	wild type control (n = 19) individuals	684:721	wild type control (n = 19) individuals	684:721	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	2	3	theme	brain	381:385	arg1	growth					387:392	slow brain growth	376:392	slow brain growth	376:392	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	1	4	theme	b-series	261:268	arg1	gangliosides					270:281	b-series gangliosides	261:281	b-series gangliosides	261:281	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	8	5	theme	plasma	1217:1222	arg1	profiles					1228:1235	Quantitative plasma GSL profiles	1204:1235	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3	1204:1286	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	10	6	theme	ST3GAL5	1703:1709	arg1	genotypes					1722:1730	ST3GAL5 c.694C > T genotypes	1703:1730	ST3GAL5 c.694C > T genotypes	1703:1730	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	6	7	from	250 μl	1099:1104	arg1	linearity					1079:1087	linearity	1079:1087	linearity from 5 to 250 μl of plasma	1079:1114	RESULTS Our method demonstrated linearity from 5 to 250 μl of plasma.
34917767	2	8	theme	Systemic	284:291	arg1	deficiency					305:314	Systemic ganglioside deficiency	284:314	Systemic ganglioside deficiency	284:314	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	9	9	theme	ganglioside	1532:1542	arg1	deficiency					1544:1553	systemic ganglioside deficiency	1523:1553	systemic ganglioside deficiency	1523:1553	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	8	10	theme	ST3GAL5	1309:1315	arg1	homozygotes					1328:1338	ST3GAL5 c.694C > T homozygotes	1309:1338	ST3GAL5 c.694C > T homozygotes	1309:1338	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	2	11	theme	infantile	335:343	arg1	retardation					363:373	infantile onset psychomotor retardation	335:373	infantile onset psychomotor retardation	335:373	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	4	12	theme	data-dependent	950:963	arg1	acquisition					965:975	neutral loss scanning and data-dependent acquisition	924:975	acquisition	965:975	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	7	13	theme	synthetic	1129:1137	arg1	GSLs					1139:1142	synthetic GSLs	1129:1142	synthetic GSLs spiked into plasma	1129:1161	Recovery of synthetic GSLs spiked into plasma was 99-104% with no matrix interference.
34917767	3	14	theme	ST3GAL5	602:608	arg1	n = 8					634:638	n = 8	634:638	n = 8	634:638	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	3	14	theme	ST3GAL5	602:608	arg1	homozygotes					621:631	ST3GAL5 c.694C > T homozygotes	602:631	ST3GAL5 c.694C > T homozygotes (n = 8)	602:639	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	9	15	theme	distinctive	1561:1571	arg1	shift					1573:1577	a distinctive shift	1559:1577	a distinctive shift in ceramide composition toward higher mass species	1559:1628	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	4	16	theme	neutral	924:930	arg1	scanning					937:944	neutral loss scanning and data-dependent acquisition	924:975	scanning	937:944	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	10	17	theme	subtle	1744:1749	arg1	heterogeneity					1762:1774	subtle structural heterogeneity	1744:1774	subtle structural heterogeneity	1744:1774	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	8	18	from	undetectable	1293:1304	arg1	homozygotes					1328:1338	ST3GAL5 c.694C > T homozygotes	1309:1338	ST3GAL5 c.694C > T homozygotes	1309:1338	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	19	theme	wild	1467:1470	arg1	6.55 ± 2.16 nmol/ml					1487:1505	6.55 ± 2.16 nmol/ml	1487:1505	6.55 ± 2.16 nmol/ml	1487:1505	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	19	theme	wild	1467:1470	arg1	controls					1477:1484	wild type controls	1467:1484	wild type controls (6.55 ± 2.16 nmol/ml)	1467:1506	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	9	20	theme	higher	1610:1615	arg1	species					1622:1628	higher mass species	1610:1628	higher mass species	1610:1628	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	0	21	theme	GM3	72:74	arg1	deficiency					88:97	human GM3 ganglioside deficiency	66:97	human GM3 ganglioside deficiency	66:97	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	3	22	theme	heterozygous	648:659	arg1	n = 24					671:676	n = 24	671:676	n = 24	671:676	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	3	22	theme	heterozygous	648:659	arg1	siblings					661:668	their heterozygous siblings	642:668	their heterozygous siblings (n = 24)	642:677	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	8	23	from	homozygotes	1328:1338	arg1	undetectable					1293:1304	undetectable	1293:1304	undetectable	1293:1304	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	24	theme	Quantitative	1204:1215	arg1	profiles					1228:1235	Quantitative plasma GSL profiles	1204:1235	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3	1204:1286	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	0	25	from	quantification	19:32	arg1	deficiency					88:97	human GM3 ganglioside deficiency	66:97	human GM3 ganglioside deficiency	66:97	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	9	26	contain	had	1555:1557	arg2	shift					1573:1577	a distinctive shift	1559:1577	a distinctive shift in ceramide composition toward higher mass species	1559:1628	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	9	26	contain	had	1555:1557	arg1	Children					1509:1516	Children	1509:1516	Children with systemic ganglioside deficiency	1509:1553	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	8	27	theme	relative	1407:1414	arg1	19.17 ± 4.20 nmol/ml					1385:1404	19.17 ± 4.20 nmol/ml	1385:1404	19.17 ± 4.20 nmol/ml	1385:1404	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	27	theme	relative	1407:1414	arg1	lactosylceramide					1367:1382	lactosylceramide	1367:1382	lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml)	1367:1506	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	1	28	theme	ST3GAL5	176:182	arg1	mutations					163:171	biallelic mutations	153:171	biallelic mutations of ST3GAL5 (c.694C > T)	153:195	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	1	29	dep	America	144:150	arg1	eliminate					197:205	eliminate	197:205	eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides	197:281	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	5	30	theme	appropriate	1014:1024	arg1	standards					1036:1044	appropriate synthetic standards	1014:1044	appropriate synthetic standards	1014:1044	Plasma GSLs were quantified against appropriate synthetic standards.
34917767	6	31	dep	demonstrated	1066:1077	arg1	RESULTS					1047:1053	RESULTS	1047:1053	RESULTS	1047:1053	RESULTS Our method demonstrated linearity from 5 to 250 μl of plasma.
34917767	10	32	theme	useful	1794:1799	arg1	strategy					1805:1812	a useful new strategy	1792:1812	a useful new strategy to diagnose and monitor GSL disorders in humans	1792:1860	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	0	33	theme	Mass	0:3	arg1	quantification					19:32	Mass spectrometric quantification	0:32	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.	0:98	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	4	34	theme	plasma	781:786	arg1	lipids					788:793	total plasma lipids	775:793	total plasma lipids	775:793	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	3	35	theme	glycosphingolipids	570:587	arg1	moieties					551:558	glycan and ceramide moieties	531:558	moieties	551:558	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	1	36	theme	biallelic	153:161	arg1	mutations					163:171	biallelic mutations	153:171	biallelic mutations of ST3GAL5 (c.694C > T)	153:195	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	3	37	theme	robust	474:479	arg1	assay					494:498	a robust quantitative assay	472:498	a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals	472:721	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	2	38	theme	cortical	431:438	arg1	impairment					447:456	cortical visual impairment	431:456	cortical visual impairment	431:456	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	0	39	theme	plasma	37:42	arg1	glycosphingolipids					44:61	plasma glycosphingolipids	37:61	plasma glycosphingolipids	37:61	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	9	40	from	shift	1573:1577	arg1	composition					1591:1601	ceramide composition	1582:1601	ceramide composition	1582:1601	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	8	41	dep	genotypes	1265:1273	arg1	GM3					1276:1278	GM3	1276:1278	GM3	1276:1278	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	41	dep	genotypes	1265:1273	arg1	genotypes					1265:1273	ST3GAL5 genotypes	1257:1273	ST3GAL5 genotypes: GM3 and GD3	1257:1286	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	41	dep	genotypes	1265:1273	arg1	GD3					1284:1286	GD3	1284:1286	GD3	1284:1286	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	4	42	theme	permethylated	843:855	arg1	column					835:840	a tC18 cartridge column	818:840	a tC18 cartridge column	818:840	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	3	43	theme	glycan	531:536	arg1	moieties					551:558	glycan and ceramide moieties	531:558	moieties	551:558	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	7	44	theme	matrix	1183:1188	arg1	interference					1190:1201	no matrix interference	1180:1201	no matrix interference	1180:1201	Recovery of synthetic GSLs spiked into plasma was 99-104% with no matrix interference.
34917767	8	45	theme	type	1472:1475	arg1	6.55 ± 2.16 nmol/ml					1487:1505	6.55 ± 2.16 nmol/ml	1487:1505	6.55 ± 2.16 nmol/ml	1487:1505	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	45	theme	type	1472:1475	arg1	controls					1477:1484	wild type controls	1467:1484	wild type controls (6.55 ± 2.16 nmol/ml)	1467:1506	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	10	46	theme	new	1801:1803	arg1	strategy					1805:1812	a useful new strategy	1792:1812	a useful new strategy to diagnose and monitor GSL disorders in humans	1792:1860	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	3	47	theme	type	689:692	arg1	individuals					711:721	wild type control (n = 19) individuals	684:721	wild type control (n = 19) individuals	684:721	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	4	48	theme	tC18	820:823	arg1	column					835:840	a tC18 cartridge column	818:840	a tC18 cartridge column	818:840	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	2	49	theme	intractable	395:405	arg1	epilepsy					407:414	intractable epilepsy	395:414	intractable epilepsy	395:414	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	1	50	theme	downstream	243:252	arg1	a-					254:255	its derivative downstream a-	228:255	its derivative downstream a-	228:255	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	10	51	theme	quantitative	1647:1658	arg1	method					1676:1681	Our quantitative glycolipidomics method	1643:1681	Our quantitative glycolipidomics method	1643:1681	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	3	52	theme	ceramide	542:549	arg1	moieties					551:558	glycan and ceramide moieties	531:558	moieties	551:558	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	4	53	theme	nanospray	875:883	arg1	spectrometry					901:912	nanospray ionization mass spectrometry	875:912	nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition	875:975	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	10	54	theme	c.694C > T	1711:1720	arg1	genotypes					1722:1730	ST3GAL5 c.694C > T genotypes	1703:1730	ST3GAL5 c.694C > T genotypes	1703:1730	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	2	55	theme	onset	345:349	arg1	retardation					363:373	infantile onset psychomotor retardation	335:373	infantile onset psychomotor retardation	335:373	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	4	56	theme	mass	896:899	arg1	spectrometry					901:912	nanospray ionization mass spectrometry	875:912	nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition	875:975	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	10	57	from	disorders	1842:1850	arg1	humans					1855:1860	humans	1855:1860	humans	1855:1860	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	2	58	theme	slow	376:379	arg1	growth					387:392	slow brain growth	376:392	slow brain growth	376:392	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	2	59	theme	ganglioside	293:303	arg1	deficiency					305:314	Systemic ganglioside deficiency	284:314	Systemic ganglioside deficiency	284:314	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	9	60	theme	systemic	1523:1530	arg1	deficiency					1544:1553	systemic ganglioside deficiency	1523:1553	systemic ganglioside deficiency	1523:1553	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	8	61	theme	GSL	1224:1226	arg1	profiles					1228:1235	Quantitative plasma GSL profiles	1204:1235	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3	1204:1286	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	6	62	dep	250 μl	1099:1104	arg1	to					1096:1097	to	1096:1097	to	1096:1097	RESULTS Our method demonstrated linearity from 5 to 250 μl of plasma.
34917767	7	63	theme	GSLs	1139:1142	arg1	Recovery					1117:1124	Recovery	1117:1124	Recovery of synthetic GSLs spiked into plasma	1117:1161	Recovery of synthetic GSLs spiked into plasma was 99-104% with no matrix interference.
34917767	3	64	theme	c.694C > T	610:619	arg1	n = 8					634:638	n = 8	634:638	n = 8	634:638	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	3	64	theme	c.694C > T	610:619	arg1	homozygotes					621:631	ST3GAL5 c.694C > T homozygotes	602:631	ST3GAL5 c.694C > T homozygotes (n = 8)	602:639	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	8	65	theme	ST3GAL5	1257:1263	arg1	GM3					1276:1278	GM3	1276:1278	GM3	1276:1278	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	65	theme	ST3GAL5	1257:1263	arg1	genotypes					1265:1273	ST3GAL5 genotypes	1257:1273	ST3GAL5 genotypes: GM3 and GD3	1257:1286	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	65	theme	ST3GAL5	1257:1263	arg1	GD3					1284:1286	GD3	1284:1286	GD3	1284:1286	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	66	theme	c.694C > T	1317:1326	arg1	homozygotes					1328:1338	ST3GAL5 c.694C > T homozygotes	1309:1338	ST3GAL5 c.694C > T homozygotes	1309:1338	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	1	67	theme	GM3	220:222	arg1	a-					254:255	its derivative downstream a-	228:255	its derivative downstream a-	228:255	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	1	67	theme	GM3	220:222	arg1	gangliosides					270:281	b-series gangliosides	261:281	b-series gangliosides	261:281	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	1	67	theme	GM3	220:222	arg1	synthesis					207:215	synthesis	207:215	synthesis of GM3	207:222	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	10	68	theme	structural	1751:1760	arg1	heterogeneity					1762:1774	subtle structural heterogeneity	1744:1774	subtle structural heterogeneity	1744:1774	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	9	69	theme	ceramide	1582:1589	arg1	composition					1591:1601	ceramide composition	1582:1601	ceramide composition	1582:1601	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	1	70	theme	America	144:150	arg1	BACKGROUND					100:109	BACKGROUND	100:109	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.	100:282	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	4	71	theme	loss	932:935	arg1	scanning					937:944	neutral loss scanning and data-dependent acquisition	924:975	scanning	937:944	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	8	72	theme	heterozygous	1419:1430	arg1	siblings					1432:1439	heterozygous siblings	1419:1439	heterozygous siblings (9.62 ± 2.46 nmol/ml)	1419:1461	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	8	72	theme	heterozygous	1419:1430	arg1	9.62 ± 2.46 nmol/ml					1442:1460	9.62 ± 2.46 nmol/ml	1442:1460	9.62 ± 2.46 nmol/ml	1442:1460	Quantitative plasma GSL profiles discriminated among ST3GAL5 genotypes: GM3 and GD3 were undetectable in ST3GAL5 c.694C > T homozygotes, who had markedly elevated lactosylceramide (19.17 ± 4.20 nmol/ml) relative to heterozygous siblings (9.62 ± 2.46 nmol/ml) and wild type controls (6.55 ± 2.16 nmol/ml).
34917767	0	73	theme	ganglioside	76:86	arg1	deficiency					88:97	human GM3 ganglioside deficiency	66:97	human GM3 ganglioside deficiency	66:97	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	9	74	theme	mass	1617:1620	arg1	species					1622:1628	higher mass species	1610:1628	higher mass species	1610:1628	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	10	75	dep	CONCLUSIONS	1631:1641	arg1	reveal					1737:1742	reveal	1737:1742	can reveal subtle structural heterogeneity	1733:1774	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	10	75	dep	CONCLUSIONS	1631:1641	arg1	represents					1781:1790	represents	1781:1790	represents a useful new strategy to diagnose and monitor GSL disorders in humans	1781:1860	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	10	75	dep	CONCLUSIONS	1631:1641	arg1	discriminates					1683:1695	discriminates	1683:1695	discriminates among ST3GAL5 c.694C > T genotypes	1683:1730	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	4	76	theme	lipids	788:793	arg1	GSLs					796:799	GSLs	796:799	GSLs	796:799	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	4	76	theme	lipids	788:793	arg1	saponification					757:770	saponification	757:770	saponification	757:770	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	4	76	theme	lipids	788:793	arg1	extraction					742:751	extraction	742:751	extraction	742:751	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	5	77	theme	synthetic	1026:1034	arg1	standards					1036:1044	appropriate synthetic standards	1014:1044	appropriate synthetic standards	1014:1044	Plasma GSLs were quantified against appropriate synthetic standards.
34917767	0	78	theme	spectrometric	5:17	arg1	quantification					19:32	Mass spectrometric quantification	0:32	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.	0:98	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	5	79	theme	Plasma	978:983	arg1	GSLs					985:988	Plasma GSLs	978:988	Plasma GSLs	978:988	Plasma GSLs were quantified against appropriate synthetic standards.
34917767	1	80	theme	Amish	117:121	arg1	communities					123:133	Amish communities	117:133	Amish communities	117:133	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	6	81	theme	plasma	1109:1114	arg1	plasma					1109:1114	plasma	1109:1114	plasma	1109:1114	RESULTS Our method demonstrated linearity from 5 to 250 μl of plasma.
34917767	6	81	theme	plasma	1109:1114	arg1	250 μl					1099:1104	250 μl	1099:1104	250 μl	1099:1104	RESULTS Our method demonstrated linearity from 5 to 250 μl of plasma.
34917767	4	82	theme	total	775:779	arg1	lipids					788:793	total plasma lipids	775:793	total plasma lipids	775:793	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	2	83	theme	visual	440:445	arg1	impairment					447:456	cortical visual impairment	431:456	cortical visual impairment	431:456	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	0	84	theme	glycosphingolipids	44:61	arg1	quantification					19:32	Mass spectrometric quantification	0:32	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.	0:98	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	4	85	theme	cartridge	825:833	arg1	column					835:840	a tC18 cartridge column	818:840	a tC18 cartridge column	818:840	METHODS Following extraction and saponification of total plasma lipids, GSLs were purified on a tC18 cartridge column, permethylated, and subjected to nanospray ionization mass spectrometry utilizing neutral loss scanning and data-dependent acquisition.
34917767	9	86	with	Children	1509:1516	arg1	deficiency					1544:1553	systemic ganglioside deficiency	1523:1553	systemic ganglioside deficiency	1523:1553	Children with systemic ganglioside deficiency had a distinctive shift in ceramide composition toward higher mass species.
34917767	3	87	theme	quantitative	481:492	arg1	assay					494:498	a robust quantitative assay	472:498	a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals	472:721	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	0	88	theme	human	66:70	arg1	deficiency					88:97	human GM3 ganglioside deficiency	66:97	human GM3 ganglioside deficiency	66:97	Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency.
34917767	3	89	theme	control	694:700	arg1	individuals					711:721	wild type control (n = 19) individuals	684:721	wild type control (n = 19) individuals	684:721	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	10	90	theme	GSL	1838:1840	arg1	disorders					1842:1850	GSL disorders	1838:1850	GSL disorders in humans	1838:1860	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	3	91	theme	wild	684:687	arg1	individuals					711:721	wild type control (n = 19) individuals	684:721	wild type control (n = 19) individuals	684:721	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	2	92	theme	psychomotor	351:361	arg1	retardation					363:373	infantile onset psychomotor retardation	335:373	infantile onset psychomotor retardation	335:373	Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment.
34917767	1	93	theme	derivative	232:241	arg1	a-					254:255	its derivative downstream a-	228:255	its derivative downstream a-	228:255	BACKGROUND Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides.
34917767	10	94	theme	glycolipidomics	1660:1674	arg1	method					1676:1681	Our quantitative glycolipidomics method	1643:1681	Our quantitative glycolipidomics method	1643:1681	CONCLUSIONS Our quantitative glycolipidomics method discriminates among ST3GAL5 c.694C > T genotypes, can reveal subtle structural heterogeneity, and represents a useful new strategy to diagnose and monitor GSL disorders in humans.
34917767	3	95	theme	plasma	563:568	arg1	GSLs					590:593	GSLs	590:593	GSLs	590:593	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
34917767	3	95	theme	plasma	563:568	arg1	glycosphingolipids					570:587	plasma glycosphingolipids	563:587	plasma glycosphingolipids (GSLs)	563:594	We developed a robust quantitative assay to simultaneously characterize glycan and ceramide moieties of plasma glycosphingolipids (GSLs) among ST3GAL5 c.694C > T homozygotes (n = 8), their heterozygous siblings (n = 24), and wild type control (n = 19) individuals.
31783892	1	0	link	N-linked	87:94	arg1	glycosylation					97:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein.
31783892	3	1	theme	Asparagine	325:334	arg1	aac					339:341	aac	339:341	aac	339:341	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	3	1	theme	Asparagine	325:334	arg1	codon					316:320	the codon	312:320	the codon of Asparagine	312:334	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	1	2	theme	PD-1	161:164	arg1	protein					166:172	immune inhibitory PD-1 protein	143:172	immune inhibitory PD-1 protein	143:172	Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein.
31783892	2	3	gly	glycosylation	193:205	arg1	PD-1					210:213	PD-1	210:213	PD-1	210:213	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	6	4	used	used	836:839	arg2	editors					821:827	the single base editors	805:827	the single base editors	805:827	Our study suggested that the single base editors can be used to augment CAR-T cell therapy.
31783892	4	5	dep	showed	557:562	arg1	downregulated					632:644	downregulated	632:644	downregulated PD-1 expression in CAR-T cells	632:675	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	4	5	dep	showed	557:562	arg1	altered					576:582	altered	576:582	altered the coding sequence of N74 residue of PDCD1	576:626	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	1	6	link	Asparagine-linked	68:84	arg1	glycosylation					97:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein.
31783892	6	7	theme	single	809:814	arg1	editors					821:827	the single base editors	805:827	the single base editors	805:827	Our study suggested that the single base editors can be used to augment CAR-T cell therapy.
31783892	5	8	theme	Further	678:684	arg1	analysis					686:693	Further analysis	678:693	Further analysis	678:693	Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo.
31783892	4	9	theme	PD-1	646:649	arg1	expression					651:660	PD-1 expression	646:660	PD-1 expression in CAR-T cells	646:675	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	4	10	theme	CAR-T	665:669	arg1	cells					671:675	CAR-T cells	665:675	CAR-T cells	665:675	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	1	11	theme	Asparagine-linked	68:84	arg1	glycosylation					97:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein.
31783892	4	12	theme	N74	607:609	arg1	residue					611:617	N74 residue	607:617	N74 residue	607:617	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	2	13	theme	CAR-T	282:286	arg1	cells					288:292	CAR-T cells	282:292	CAR-T cells	282:292	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	3	14	theme	adenine	370:376	arg1	ABE					391:393	ABE	391:393	ABE	391:393	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	3	14	theme	adenine	370:376	arg1	editor					383:388	the adenine base editor	366:388	the adenine base editor (ABE)	366:394	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	1	15	theme	N-linked	87:94	arg1	glycosylation					97:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation	68:109	Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein.
31783892	3	16	theme	base	378:381	arg1	ABE					391:393	ABE	391:393	ABE	391:393	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	3	16	theme	base	378:381	arg1	editor					383:388	the adenine base editor	366:388	the adenine base editor (ABE)	366:394	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	2	17	link	N-linked	184:191	arg1	glycosylation					193:205	Reducing N-linked glycosylation	175:205	Reducing N-linked glycosylation of PD-1	175:213	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	0	18	theme	PD-1	27:30	arg1	glycosylation					10:22	glycosylation	10:22	glycosylation of PD-1 to enhance CAR-T cell cytotoxicity	10:65	Targeting glycosylation of PD-1 to enhance CAR-T cell cytotoxicity.
31783892	3	19	theme	PD-1	475:478	arg1	suppression					480:490	PD-1 suppression	475:490	PD-1 suppression	475:490	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	6	20	theme	base	816:819	arg1	editors					821:827	the single base editors	805:827	the single base editors	805:827	Our study suggested that the single base editors can be used to augment CAR-T cell therapy.
31783892	3	21	theme	glycosylated	508:519	arg1	residue					521:527	the glycosylated residue	504:527	the glycosylated residue in CAR-T cells	504:542	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	6	22	theme	CAR-T	852:856	arg1	therapy					863:869	CAR-T cell therapy	852:869	CAR-T cell therapy	852:869	Our study suggested that the single base editors can be used to augment CAR-T cell therapy.
31783892	5	23	theme	enhanced	729:736	arg1	functions					748:756	enhanced cytotoxic functions	729:756	enhanced cytotoxic functions	729:756	Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo.
31783892	2	24	theme	N-linked	184:191	arg1	glycosylation					193:205	Reducing N-linked glycosylation	175:205	Reducing N-linked glycosylation of PD-1	175:213	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	2	25	from	effects	271:277	arg1	cells					288:292	CAR-T cells	282:292	CAR-T cells	282:292	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	5	26	theme	cytotoxic	738:746	arg1	functions					748:756	enhanced cytotoxic functions	729:756	enhanced cytotoxic functions	729:756	Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo.
31783892	2	27	theme	Reducing	175:182	arg1	glycosylation					193:205	Reducing N-linked glycosylation	175:205	Reducing N-linked glycosylation of PD-1	175:213	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	0	28	gly	glycosylation	10:22	arg1	PD-1					27:30	PD-1	27:30	PD-1	27:30	Targeting glycosylation of PD-1 to enhance CAR-T cell cytotoxicity.
31783892	3	29	theme	g·c	418:420	arg1	conversion					422:431	g·c conversion	418:431	g·c conversion	418:431	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	0	30	theme	cell	49:52	arg1	cytotoxicity					54:65	CAR-T cell cytotoxicity	43:65	CAR-T cell cytotoxicity	43:65	Targeting glycosylation of PD-1 to enhance CAR-T cell cytotoxicity.
31783892	3	31	theme	CAR-T	532:536	arg1	cells					538:542	CAR-T cells	532:542	CAR-T cells	532:542	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	0	32	theme	CAR-T	43:47	arg1	cytotoxicity					54:65	CAR-T cell cytotoxicity	43:65	CAR-T cell cytotoxicity	43:65	Targeting glycosylation of PD-1 to enhance CAR-T cell cytotoxicity.
31783892	5	33	dep	showed	695:700	arg1	had					725:727	had	725:727	showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo	695:777	Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo.
31783892	2	34	theme	PD-1	228:231	arg1	expression					233:242	PD-1 expression	228:242	PD-1 expression	228:242	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	4	35	theme	residue	611:617	arg1	sequence					595:602	the coding sequence	584:602	the coding sequence of N74 residue of PDCD1	584:626	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	3	36	used	used	460:463	arg2	ABE					391:393	ABE	391:393	ABE	391:393	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	3	36	used	used	460:463	arg2	editor					383:388	the adenine base editor	366:388	the adenine base editor (ABE)	366:394	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	3	37	gly	glycosylated	508:519	arg1	residue					521:527	the glycosylated residue	504:527	the glycosylated residue in CAR-T cells	504:542	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	2	38	theme	PD-1	210:213	arg1	glycosylation					193:205	Reducing N-linked glycosylation	175:205	Reducing N-linked glycosylation of PD-1	175:213	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	4	39	theme	PDCD1	622:626	arg1	sequence					595:602	the coding sequence	584:602	the coding sequence of N74 residue of PDCD1	584:626	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	3	40	from	residue	521:527	arg1	cells					538:542	CAR-T cells	532:542	CAR-T cells	532:542	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	3	41	theme	specific	436:443	arg1	site					445:448	specific site	436:448	specific site	436:448	Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells.
31783892	5	42	theme	ABE-edited	702:711	arg1	cells					719:723	ABE-edited CAR-T cells	702:723	ABE-edited CAR-T cells	702:723	Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo.
31783892	4	43	theme	coding	588:593	arg1	sequence					595:602	the coding sequence	584:602	the coding sequence of N74 residue of PDCD1	584:626	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	2	44	theme	inhibitory	260:269	arg1	effects					271:277	its inhibitory effects	256:277	its inhibitory effects on CAR-T cells	256:292	Reducing N-linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells.
31783892	1	45	theme	immune	143:148	arg1	protein					166:172	immune inhibitory PD-1 protein	143:172	immune inhibitory PD-1 protein	143:172	Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein.
31783892	4	46	from	expression	651:660	arg1	cells					671:675	CAR-T cells	665:675	CAR-T cells	665:675	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
31783892	5	47	theme	CAR-T	713:717	arg1	cells					719:723	ABE-edited CAR-T cells	702:723	ABE-edited CAR-T cells	702:723	Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo.
31783892	6	48	theme	cell	858:861	arg1	therapy					863:869	CAR-T cell therapy	852:869	CAR-T cell therapy	852:869	Our study suggested that the single base editors can be used to augment CAR-T cell therapy.
31783892	1	49	theme	inhibitory	150:159	arg1	protein					166:172	immune inhibitory PD-1 protein	143:172	immune inhibitory PD-1 protein	143:172	Asparagine-linked (N-linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein.
31783892	4	50	theme	ABE	564:566	arg1	editing					568:574	ABE editing	564:574	ABE editing	564:574	Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells.
30392906	3	0	from	function	345:352	arg1	development					405:415	HCC development	401:415	HCC development	401:415	However, function of MPZL1 as a receptor of ConA and its role in HCC development are largely unknown.
30392906	7	1	theme	hydrogen	867:874	arg1	bonds					876:880	hydrogen bonds	867:880	hydrogen bonds between Ser86 and Val145	867:905	Furthermore, we also found that MPZL1 exists as a homodimer in the crystal, in which hydrogen bonds between Ser86 and Val145 play an important role.
30392906	4	2	theme	crystal	496:502	arg1	structure					504:512	the crystal structure	492:512	the crystal structure of the extracellular domain of MPZL1	492:549	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30392906	0	3	theme	protein	73:79	arg1	protein					73:79	Myelin protein	66:79	Myelin protein	66:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	0	3	theme	protein	73:79	arg1	domain					56:61	the extracellular domain	38:61	the extracellular domain of Myelin protein	38:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	1	4	theme	concanavalin	218:229	arg1	ConA					234:237	ConA	234:237	ConA	234:237	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	4	theme	concanavalin	218:229	arg1	A					231:231	concanavalin A	218:231	concanavalin A (ConA)	218:238	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	9	5	from	transmission	1112:1123	arg1	adhesion					1133:1140	cell adhesion	1128:1140	cell adhesion	1128:1140	We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.
30392906	1	6	theme	A	231:231	arg1	protein					127:133	Myelin protein zero-like protein 1	102:135	Myelin protein zero-like protein 1 (MPZL1)	102:143	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	6	theme	A	231:231	arg1	receptor					206:213	a receptor	204:213	a receptor of concanavalin A (ConA)	204:238	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	6	theme	A	231:231	arg1	member					150:155	a member	148:155	a member of the immunoglobulin superfamily	148:189	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	8	7	theme	ConA	1030:1033	arg1	receptor					1018:1025	a receptor	1016:1025	a receptor of ConA	1016:1033	Our results demonstrate that glycosylation of Asn50 is essential for its function as a receptor of ConA.
30392906	6	8	theme	glycosylation	705:717	arg1	site					719:722	a unique glycosylation site	696:722	a unique glycosylation site	696:722	Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA.
30392906	6	8	theme	glycosylation	705:717	arg1	Asn50					687:691	Asn50	687:691	Asn50	687:691	Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA.
30392906	8	9	gly	glycosylation	960:972	arg1	Asn50					977:981	Asn50	977:981	Asn50	977:981	Our results demonstrate that glycosylation of Asn50 is essential for its function as a receptor of ConA.
30392906	9	10	from	control	1090:1096	arg1	adhesion					1133:1140	cell adhesion	1128:1140	cell adhesion	1128:1140	We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.
30392906	4	11	theme	MPZL1	545:549	arg1	MPZL1					545:549	MPZL1	545:549	MPZL1	545:549	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30392906	4	11	theme	MPZL1	545:549	arg1	domain					535:540	the extracellular domain	517:540	the extracellular domain of MPZL1	517:549	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30392906	6	12	with	interaction	759:769	arg1	ConA					776:779	ConA	776:779	ConA	776:779	Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA.
30392906	9	13	from	adhesion	1133:1140	arg1	control					1090:1096	control	1090:1096	control of its signal transmission in cell adhesion	1090:1140	We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.
30392906	2	14	theme	hepatocellular	265:278	arg1	HCC					291:293	HCC	291:293	HCC	291:293	MPZL1 is upregulated in hepatocellular carcinoma (HCC) and accelerates migration of HCC cells.
30392906	2	14	theme	hepatocellular	265:278	arg1	carcinoma					280:288	hepatocellular carcinoma	265:288	hepatocellular carcinoma (HCC)	265:294	MPZL1 is upregulated in hepatocellular carcinoma (HCC) and accelerates migration of HCC cells.
30392906	2	15	theme	cells	329:333	arg1	migration					312:320	migration	312:320	migration of HCC cells	312:333	MPZL1 is upregulated in hepatocellular carcinoma (HCC) and accelerates migration of HCC cells.
30392906	0	16	theme	Structural	0:9	arg1	studies					27:33	Structural and biochemical studies	0:33	Structural and biochemical studies of the extracellular domain of Myelin protein	0:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	2	17	theme	HCC	325:327	arg1	cells					329:333	HCC cells	325:333	HCC cells	325:333	MPZL1 is upregulated in hepatocellular carcinoma (HCC) and accelerates migration of HCC cells.
30392906	5	18	theme	immunoglobulin	605:618	arg1	domain					634:639	a typical immunoglobulin variable-like domain	595:639	a typical immunoglobulin variable-like domain that is much like MPZ	595:661	Overall, it folds like a typical immunoglobulin variable-like domain that is much like MPZ.
30392906	6	19	theme	unique	698:703	arg1	site					719:722	a unique glycosylation site	696:722	a unique glycosylation site	696:722	Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA.
30392906	6	19	theme	unique	698:703	arg1	Asn50					687:691	Asn50	687:691	Asn50	687:691	Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA.
30392906	1	20	theme	immunoglobulin	164:177	arg1	superfamily					179:189	the immunoglobulin superfamily	160:189	the immunoglobulin superfamily	160:189	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	0	21	theme	biochemical	15:25	arg1	studies					27:33	Structural and biochemical studies	0:33	Structural and biochemical studies of the extracellular domain of Myelin protein	0:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	5	22	theme	variable-like	620:632	arg1	domain					634:639	a typical immunoglobulin variable-like domain	595:639	a typical immunoglobulin variable-like domain that is much like MPZ	595:661	Overall, it folds like a typical immunoglobulin variable-like domain that is much like MPZ.
30392906	1	23	theme	Myelin	102:107	arg1	protein					127:133	Myelin protein zero-like protein 1	102:135	Myelin protein zero-like protein 1 (MPZL1)	102:143	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	23	theme	Myelin	102:107	arg1	MPZL1					138:142	MPZL1	138:142	MPZL1	138:142	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	23	theme	Myelin	102:107	arg1	member					150:155	a member	148:155	a member of the immunoglobulin superfamily	148:189	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	24	theme	superfamily	179:189	arg1	protein					127:133	Myelin protein zero-like protein 1	102:135	Myelin protein zero-like protein 1 (MPZL1)	102:143	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	24	theme	superfamily	179:189	arg1	receptor					206:213	a receptor	204:213	a receptor of concanavalin A (ConA)	204:238	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	24	theme	superfamily	179:189	arg1	member					150:155	a member	148:155	a member of the immunoglobulin superfamily	148:189	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	9	25	theme	signal	1105:1110	arg1	transmission					1112:1123	its signal transmission	1101:1123	its signal transmission in cell adhesion	1101:1140	We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.
30392906	3	26	theme	ConA	380:383	arg1	receptor					368:375	a receptor	366:375	a receptor of ConA	366:383	However, function of MPZL1 as a receptor of ConA and its role in HCC development are largely unknown.
30392906	3	27	theme	MPZL1	357:361	arg1	function					345:352	function	345:352	function of MPZL1 as a receptor of ConA	345:383	However, function of MPZL1 as a receptor of ConA and its role in HCC development are largely unknown.
30392906	3	27	theme	MPZL1	357:361	arg1	role					393:396	its role	389:396	its role in HCC development	389:415	However, function of MPZL1 as a receptor of ConA and its role in HCC development are largely unknown.
30392906	8	28	theme	Asn50	977:981	arg1	glycosylation					960:972	glycosylation	960:972	glycosylation of Asn50	960:981	Our results demonstrate that glycosylation of Asn50 is essential for its function as a receptor of ConA.
30392906	9	29	theme	transmission	1112:1123	arg1	control					1090:1096	control	1090:1096	control of its signal transmission in cell adhesion	1090:1140	We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.
30392906	7	30	theme	important	915:923	arg1	role					925:928	an important role	912:928	an important role	912:928	Furthermore, we also found that MPZL1 exists as a homodimer in the crystal, in which hydrogen bonds between Ser86 and Val145 play an important role.
30392906	4	31	theme	2.7 Å	554:558	arg1	resolution					560:569	2.7 Å resolution	554:569	2.7 Å resolution	554:569	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30392906	0	32	theme	domain	56:61	arg1	studies					27:33	Structural and biochemical studies	0:33	Structural and biochemical studies of the extracellular domain of Myelin protein	0:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	6	33	gly	glycosylation	705:717	arg2	site					719:722	a unique glycosylation site	696:722	a unique glycosylation site	696:722	Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA.
30392906	6	33	gly	glycosylation	705:717	arg2	Asn50					687:691	Asn50	687:691	Asn50	687:691	Unexpectedly, we found Asn50 is a unique glycosylation site and the glycosylation mediates its interaction with ConA.
30392906	1	34	theme	protein	109:115	arg1	protein					127:133	Myelin protein zero-like protein 1	102:135	Myelin protein zero-like protein 1 (MPZL1)	102:143	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	34	theme	protein	109:115	arg1	MPZL1					138:142	MPZL1	138:142	MPZL1	138:142	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	34	theme	protein	109:115	arg1	member					150:155	a member	148:155	a member of the immunoglobulin superfamily	148:189	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	0	35	theme	extracellular	42:54	arg1	protein					73:79	Myelin protein	66:79	Myelin protein	66:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	0	35	theme	extracellular	42:54	arg1	domain					56:61	the extracellular domain	38:61	the extracellular domain of Myelin protein	38:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	9	36	theme	cell	1128:1131	arg1	adhesion					1133:1140	cell adhesion	1128:1140	cell adhesion	1128:1140	We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.
30392906	1	37	theme	zero-like	117:125	arg1	protein					127:133	Myelin protein zero-like protein 1	102:135	Myelin protein zero-like protein 1 (MPZL1)	102:143	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	37	theme	zero-like	117:125	arg1	MPZL1					138:142	MPZL1	138:142	MPZL1	138:142	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	1	37	theme	zero-like	117:125	arg1	member					150:155	a member	148:155	a member of the immunoglobulin superfamily	148:189	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	4	38	theme	functional	455:464	arg1	basis					466:470	the functional basis	451:470	the functional basis	451:470	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30392906	3	39	from	role	393:396	arg1	development					405:415	HCC development	401:415	HCC development	401:415	However, function of MPZL1 as a receptor of ConA and its role in HCC development are largely unknown.
30392906	7	40	from	homodimer	832:840	arg1	crystal					849:855	the crystal	845:855	the crystal	845:855	Furthermore, we also found that MPZL1 exists as a homodimer in the crystal, in which hydrogen bonds between Ser86 and Val145 play an important role.
30392906	4	41	theme	extracellular	521:533	arg1	MPZL1					545:549	MPZL1	545:549	MPZL1	545:549	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30392906	4	41	theme	extracellular	521:533	arg1	domain					535:540	the extracellular domain	517:540	the extracellular domain of MPZL1	517:549	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30392906	5	42	theme	typical	597:603	arg1	domain					634:639	a typical immunoglobulin variable-like domain	595:639	a typical immunoglobulin variable-like domain that is much like MPZ	595:661	Overall, it folds like a typical immunoglobulin variable-like domain that is much like MPZ.
30392906	3	43	theme	HCC	401:403	arg1	development					405:415	HCC development	401:415	HCC development	401:415	However, function of MPZL1 as a receptor of ConA and its role in HCC development are largely unknown.
30392906	9	44	theme	MPZL1	1068:1072	arg1	dimerization					1052:1063	dimerization	1052:1063	dimerization of MPZL1	1052:1072	We propose that dimerization of MPZL1 participates in control of its signal transmission in cell adhesion.
30392906	0	45	theme	Myelin	66:71	arg1	protein					73:79	Myelin protein	66:79	Myelin protein	66:79	Structural and biochemical studies of the extracellular domain of Myelin protein zero-like protein 1.
30392906	1	46	theme	a	204:204	arg1	receptor					206:213	a receptor	204:213	a receptor of concanavalin A (ConA)	204:238	Myelin protein zero-like protein 1 (MPZL1) is a member of the immunoglobulin superfamily, and is also a receptor of concanavalin A (ConA).
30392906	4	47	theme	domain	535:540	arg1	structure					504:512	the crystal structure	492:512	the crystal structure of the extracellular domain of MPZL1	492:549	To elucidate the functional basis, we have determined the crystal structure of the extracellular domain of MPZL1 at 2.7 Å resolution.
30733333	9	0	theme	specific	1426:1433	arg1	dismutase					1480:1488	superoxide dismutase 2	1469:1490	superoxide dismutase 2 (SOD2)	1469:1497	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	9	0	theme	specific	1426:1433	arg1	proteins					1449:1456	specific mitochondrial proteins	1426:1456	specific mitochondrial proteins	1426:1456	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	6	1	theme	hydrolase	915:923	arg1	O-GlcNAcase					925:935	the O-GlcNAc hydrolase O-GlcNAcase	902:935	the O-GlcNAc hydrolase O-GlcNAcase	902:935	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	3	2	located	detected	587:594	arg1	factors					641:647	several eukaryotic translation initiation factors	599:647	several eukaryotic translation initiation factors	599:647	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	3	2	located	detected	587:594	arg1	proteins					663:670	ribosomal proteins	653:670	ribosomal proteins	653:670	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	3	2	located	detected	587:594	arg2	O-GlcNAcylation					557:571	O-GlcNAcylation	557:571	O-GlcNAcylation	557:571	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	9	3	theme	proteins	1449:1456	arg1	translation					1411:1421	translation	1411:1421	translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2),	1411:1498	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	8	4	theme	ribosome	1252:1259	arg1	occupancy					1261:1269	ribosome occupancy	1252:1269	ribosome occupancy	1252:1269	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	10	5	theme	superoxide	1595:1604	arg1	levels					1606:1611	mitochondrial superoxide levels	1581:1611	mitochondrial superoxide levels in WT cells	1581:1623	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	1	6	theme	O-linked	201:208	arg1	addition					210:217	O-linked addition	201:217	O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins	201:277	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	12	7	theme	mRNAs	2047:2051	arg1	selection					2034:2042	the selection	2030:2042	the selection of mRNAs for translation	2030:2067	These findings provide evidence for a mechanism whereby diabetes-induced O-GlcNAcylation promotes oxidative stress in the retina by altering the selection of mRNAs for translation.
30733333	8	8	theme	1912	1277:1280	arg1	mRNAs					1282:1286	1912 mRNAs	1277:1286	1912 mRNAs	1277:1286	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	10	9	theme	O-GlcNAcylation-induced	1658:1680	arg1	superoxide					1696:1705	O-GlcNAcylation-induced mitochondrial superoxide	1658:1705	O-GlcNAcylation-induced mitochondrial superoxide	1658:1705	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	3	10	theme	translation	618:628	arg1	factors					641:647	several eukaryotic translation initiation factors	599:647	several eukaryotic translation initiation factors	599:647	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	7	11	located	observed	1049:1056	arg1	mRNAs					1081:1085	ribosome-associated mRNAs	1061:1085	ribosome-associated mRNAs (i.e. mRNAs undergoing translation)	1061:1121	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	7	11	located	observed	1049:1056	arg2	effect					1004:1009	The principal effect	990:1009	The principal effect of TMG on retinal gene expression	990:1043	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	11	12	theme	diabetic	1855:1862	arg1	mice					1883:1886	diabetic 4E-BP1/2-deficient mice	1855:1886	diabetic 4E-BP1/2-deficient mice	1855:1886	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	5	13	from	effect	791:796	arg1	expression					842:851	retinal gene expression	829:851	retinal gene expression	829:851	Here, using ribosome profiling, we evaluated the effect of enhanced O-GlcNAcylation on retinal gene expression.
30733333	3	14	theme	several	599:605	arg1	factors					641:647	several eukaryotic translation initiation factors	599:647	several eukaryotic translation initiation factors	599:647	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	7	15	theme	gene	1029:1032	arg1	expression					1034:1043	retinal gene expression	1021:1043	retinal gene expression	1021:1043	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	6	16	theme	enhanced	948:955	arg1	O-GlcNAcylation					973:987	enhanced retinal protein O-GlcNAcylation	948:987	enhanced retinal protein O-GlcNAcylation	948:987	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	11	17	theme	reactive	1797:1804	arg1	species					1813:1819	reactive oxygen species	1797:1819	increased reactive oxygen species levels	1787:1826	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	7	18	theme	ribosome-associated	1061:1079	arg1	mRNAs					1081:1085	ribosome-associated mRNAs	1061:1085	ribosome-associated mRNAs (i.e. mRNAs undergoing translation)	1061:1121	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	3	19	theme	ribosomal	653:661	arg1	proteins					663:670	ribosomal proteins	653:670	ribosomal proteins	653:670	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	2	20	theme	initiation	518:527	arg1	eIF4E					537:541	eIF4E	537:541	eIF4E	537:541	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	20	theme	initiation	518:527	arg1	factor					529:534	eukaryotic translation initiation factor	495:534	the cap-binding protein eukaryotic translation initiation factor (eIF4E)	471:542	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	0	21	from	dysfunction	106:116	arg1	retina					125:130	the retina	121:130	the retina	121:130	O-GlcNAcylation alters the selection of mRNAs for translation and promotes 4E-BP1-dependent mitochondrial dysfunction in the retina.
30733333	3	22	gly	O-GlcNAcylation	557:571	arg1	factors					641:647	several eukaryotic translation initiation factors	599:647	several eukaryotic translation initiation factors	599:647	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	3	22	gly	O-GlcNAcylation	557:571	arg1	proteins					663:670	ribosomal proteins	653:670	ribosomal proteins	653:670	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	12	23	from	stress	1997:2002	arg1	retina					2011:2016	the retina	2007:2016	the retina	2007:2016	These findings provide evidence for a mechanism whereby diabetes-induced O-GlcNAcylation promotes oxidative stress in the retina by altering the selection of mRNAs for translation.
30733333	2	24	theme	eukaryotic	495:504	arg1	eIF4E					537:541	eIF4E	537:541	eIF4E	537:541	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	24	theme	eukaryotic	495:504	arg1	factor					529:534	eukaryotic translation initiation factor	495:534	the cap-binding protein eukaryotic translation initiation factor (eIF4E)	471:542	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	6	25	theme	O-GlcNAc	906:913	arg1	O-GlcNAcase					925:935	the O-GlcNAc hydrolase O-GlcNAcase	902:935	the O-GlcNAc hydrolase O-GlcNAcase	902:935	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	0	26	theme	4E-BP1-dependent	75:90	arg1	dysfunction					106:116	4E-BP1-dependent mitochondrial dysfunction	75:116	4E-BP1-dependent mitochondrial dysfunction in the retina	75:130	O-GlcNAcylation alters the selection of mRNAs for translation and promotes 4E-BP1-dependent mitochondrial dysfunction in the retina.
30733333	7	27	theme	principal	994:1002	arg1	effect					1004:1009	The principal effect	990:1009	The principal effect of TMG on retinal gene expression	990:1043	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	1	28	theme	proteins	189:196	arg1	modification					173:184	the posttranslational modification	151:184	the posttranslational modification of proteins	151:196	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	11	29	theme	species	1813:1819	arg1	levels					1821:1826	increased reactive oxygen species levels	1787:1826	increased reactive oxygen species levels	1787:1826	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	11	29	theme	species	1813:1819	arg1	effect					1832:1837	an effect	1829:1837	an effect not observed in diabetic 4E-BP1/2-deficient mice	1829:1886	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	0	30	theme	mRNAs	40:44	arg1	selection					27:35	the selection	23:35	the selection of mRNAs for translation	23:60	O-GlcNAcylation alters the selection of mRNAs for translation and promotes 4E-BP1-dependent mitochondrial dysfunction in the retina.
30733333	2	31	theme	eIF4E-binding	397:409	arg1	protein					411:417	eIF4E-binding protein 1	397:419	eIF4E-binding protein 1 (4E-BP1)	397:428	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	31	theme	eIF4E-binding	397:409	arg1	4E-BP1					422:427	4E-BP1	422:427	4E-BP1	422:427	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	31	theme	eIF4E-binding	397:409	arg1	repressor					366:374	the repressor	362:374	the repressor of mRNA translation	362:394	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	8	32	theme	increased	1325:1333	arg1	rates					1349:1353	increased translational rates	1325:1353	increased translational rates	1325:1353	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	2	33	theme	cap-binding	475:485	arg1	protein					487:493	the cap-binding protein eukaryotic translation initiation factor (eIF4E)	471:542	the cap-binding protein eukaryotic translation initiation factor (eIF4E)	471:542	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	4	34	theme	functional	686:695	arg1	unknown					733:739	unknown	733:739	unknown	733:739	However, the functional consequence of this modification is unknown.
30733333	4	34	theme	functional	686:695	arg1	consequence					697:707	the functional consequence	682:707	the functional consequence of this modification	682:728	However, the functional consequence of this modification is unknown.
30733333	5	35	theme	O-GlcNAcylation	810:824	arg1	effect					791:796	the effect	787:796	the effect of enhanced O-GlcNAcylation on retinal gene expression	787:851	Here, using ribosome profiling, we evaluated the effect of enhanced O-GlcNAcylation on retinal gene expression.
30733333	10	36	theme	cellular	1547:1554	arg1	respiration					1556:1566	cellular respiration	1547:1566	cellular respiration	1547:1566	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	5	37	theme	retinal	829:835	arg1	expression					842:851	retinal gene expression	829:851	retinal gene expression	829:851	Here, using ribosome profiling, we evaluated the effect of enhanced O-GlcNAcylation on retinal gene expression.
30733333	2	38	dep	protein	487:493	arg1	eIF4E					537:541	eIF4E	537:541	eIF4E	537:541	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	38	dep	protein	487:493	arg1	factor					529:534	eukaryotic translation initiation factor	495:534	the cap-binding protein eukaryotic translation initiation factor (eIF4E)	471:542	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	10	39	from	levels	1606:1611	arg1	cells					1619:1623	WT cells	1616:1623	WT cells	1616:1623	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	11	40	theme	mice	1772:1775	arg1	retina					1750:1755	The retina	1746:1755	The retina of diabetic WT mice	1746:1775	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	2	41	theme	mice	356:359	arg1	retina					337:342	the retina	333:342	the retina of diabetic mice	333:359	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	9	42	theme	O-GlcNAcase	1385:1395	arg1	inhibition					1397:1406	O-GlcNAcase inhibition	1385:1406	O-GlcNAcase inhibition	1385:1406	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	6	43	theme	thiamet	869:875	arg1	G					877:877	thiamet G	869:877	thiamet G (TMG)	869:883	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	6	43	theme	thiamet	869:875	arg1	inhibitor					889:897	an inhibitor	886:897	an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase	886:935	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	6	43	theme	thiamet	869:875	arg1	TMG					880:882	TMG	880:882	TMG	880:882	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	10	44	theme	mitochondrial	1581:1593	arg1	levels					1606:1611	mitochondrial superoxide levels	1581:1611	mitochondrial superoxide levels in WT cells	1581:1623	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	11	45	theme	diabetic	1760:1767	arg1	mice					1772:1775	diabetic WT mice	1760:1775	diabetic WT mice	1760:1775	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	2	46	theme	translation	384:394	arg1	protein					411:417	eIF4E-binding protein 1	397:419	eIF4E-binding protein 1 (4E-BP1)	397:428	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	46	theme	translation	384:394	arg1	O-GlcNAcylated					434:447	O-GlcNAcylated	434:447	O-GlcNAcylated	434:447	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	46	theme	translation	384:394	arg1	repressor					366:374	the repressor	362:374	the repressor of mRNA translation	362:394	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	1	47	theme	proteins	270:277	arg1	residues					258:265	Ser/Thr residues	250:265	Ser/Thr residues of proteins	250:277	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	1	47	theme	proteins	270:277	arg1	proteins					270:277	proteins	270:277	proteins	270:277	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	6	48	theme	O-GlcNAcase	925:935	arg1	G					877:877	thiamet G	869:877	thiamet G (TMG)	869:883	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	6	48	theme	O-GlcNAcase	925:935	arg1	inhibitor					889:897	an inhibitor	886:897	an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase	886:935	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	10	49	theme	WT	1616:1617	arg1	cells					1619:1623	WT cells	1616:1623	WT cells	1616:1623	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	9	50	theme	mitochondrial	1435:1447	arg1	dismutase					1480:1488	superoxide dismutase 2	1469:1490	superoxide dismutase 2 (SOD2)	1469:1497	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	9	50	theme	mitochondrial	1435:1447	arg1	proteins					1449:1456	specific mitochondrial proteins	1426:1456	specific mitochondrial proteins	1426:1456	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	8	51	from	changes	1241:1247	arg1	occupancy					1261:1269	ribosome occupancy	1252:1269	ribosome occupancy	1252:1269	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	7	52	dep	mRNAs	1081:1085	arg1	mRNAs					1093:1097	mRNAs	1093:1097	mRNAs undergoing translation	1093:1120	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	10	53	theme	4E-BP1/2	1630:1637	arg1	deletion					1639:1646	4E-BP1/2 deletion	1630:1646	4E-BP1/2 deletion	1630:1646	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	11	54	located	observed	1843:1850	arg2	effect					1832:1837	an effect	1829:1837	an effect not observed in diabetic 4E-BP1/2-deficient mice	1829:1886	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	11	54	located	observed	1843:1850	arg2	levels					1821:1826	increased reactive oxygen species levels	1787:1826	increased reactive oxygen species levels	1787:1826	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	11	54	located	observed	1843:1850	arg1	mice					1883:1886	diabetic 4E-BP1/2-deficient mice	1855:1886	diabetic 4E-BP1/2-deficient mice	1855:1886	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	9	55	theme	superoxide	1469:1478	arg1	dismutase					1480:1488	superoxide dismutase 2	1469:1490	superoxide dismutase 2 (SOD2)	1469:1497	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	9	55	theme	superoxide	1469:1478	arg1	SOD2					1493:1496	SOD2	1493:1496	SOD2	1493:1496	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	1	56	theme	GlcNAc	222:227	arg1	addition					210:217	O-linked addition	201:217	O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins	201:277	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	7	57	from	effect	1004:1009	arg1	expression					1034:1043	retinal gene expression	1021:1043	retinal gene expression	1021:1043	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	10	58	theme	mitochondrial	1682:1694	arg1	superoxide					1696:1705	O-GlcNAcylation-induced mitochondrial superoxide	1658:1705	O-GlcNAcylation-induced mitochondrial superoxide	1658:1705	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	3	59	theme	eukaryotic	607:616	arg1	factors					641:647	several eukaryotic translation initiation factors	599:647	several eukaryotic translation initiation factors	599:647	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	8	60	theme	transcriptome	1205:1217	arg1	%					1196:1196	∼19%	1193:1196	∼19% of the transcriptome	1193:1217	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	8	60	theme	transcriptome	1205:1217	arg1	transcriptome					1205:1217	the transcriptome	1201:1217	the transcriptome	1201:1217	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	8	61	theme	TMG-induced	1229:1239	arg1	changes					1241:1247	TMG-induced changes	1229:1247	TMG-induced changes in ribosome occupancy	1229:1269	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	6	62	theme	retinal	957:963	arg1	O-GlcNAcylation					973:987	enhanced retinal protein O-GlcNAcylation	948:987	enhanced retinal protein O-GlcNAcylation	948:987	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
30733333	11	63	theme	4E-BP1/2-deficient	1864:1881	arg1	mice					1883:1886	diabetic 4E-BP1/2-deficient mice	1855:1886	diabetic 4E-BP1/2-deficient mice	1855:1886	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	8	64	theme	1683	1307:1310	arg1	mRNAs					1312:1316	1683 mRNAs	1307:1316	1683 mRNAs	1307:1316	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	11	65	theme	oxygen	1806:1811	arg1	species					1813:1819	reactive oxygen species	1797:1819	increased reactive oxygen species levels	1787:1826	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	3	66	theme	initiation	630:639	arg1	factors					641:647	several eukaryotic translation initiation factors	599:647	several eukaryotic translation initiation factors	599:647	O-GlcNAcylation has also been detected on several eukaryotic translation initiation factors and ribosomal proteins.
30733333	7	67	theme	retinal	1021:1027	arg1	expression					1034:1043	retinal gene expression	1021:1043	retinal gene expression	1021:1043	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	1	68	theme	posttranslational	155:171	arg1	modification					173:184	the posttranslational modification	151:184	the posttranslational modification of proteins	151:196	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	2	69	theme	translation	506:516	arg1	eIF4E					537:541	eIF4E	537:541	eIF4E	537:541	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	69	theme	translation	506:516	arg1	factor					529:534	eukaryotic translation initiation factor	495:534	the cap-binding protein eukaryotic translation initiation factor (eIF4E)	471:542	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	70	from	O-GlcNAcylated	434:447	arg1	retina					337:342	the retina	333:342	the retina of diabetic mice	333:359	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	11	71	theme	increased	1787:1795	arg1	levels					1821:1826	increased reactive oxygen species levels	1787:1826	increased reactive oxygen species levels	1787:1826	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	11	71	theme	increased	1787:1795	arg1	effect					1832:1837	an effect	1829:1837	an effect not observed in diabetic 4E-BP1/2-deficient mice	1829:1886	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	0	72	theme	mitochondrial	92:104	arg1	dysfunction					106:116	4E-BP1-dependent mitochondrial dysfunction	75:116	4E-BP1-dependent mitochondrial dysfunction in the retina	75:130	O-GlcNAcylation alters the selection of mRNAs for translation and promotes 4E-BP1-dependent mitochondrial dysfunction in the retina.
30733333	9	73	from	effect	1375:1380	arg1	translation					1411:1421	translation	1411:1421	translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2),	1411:1498	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	7	74	theme	TMG	1014:1016	arg1	effect					1004:1009	The principal effect	990:1009	The principal effect of TMG on retinal gene expression	990:1043	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	2	75	theme	protein	487:493	arg1	sequestration					454:466	sequestration	454:466	sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E)	454:542	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	7	76	from	changes	1159:1165	arg1	abundance					1170:1178	abundance	1170:1178	abundance	1170:1178	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	8	77	theme	translational	1335:1347	arg1	rates					1349:1353	increased translational rates	1325:1353	increased translational rates	1325:1353	Remarkably, ∼19% of the transcriptome exhibited TMG-induced changes in ribosome occupancy, with 1912 mRNAs having reduced and 1683 mRNAs having increased translational rates.
30733333	5	78	theme	ribosome	754:761	arg1	profiling					763:771	ribosome profiling	754:771	ribosome profiling	754:771	Here, using ribosome profiling, we evaluated the effect of enhanced O-GlcNAcylation on retinal gene expression.
30733333	2	79	from	retina	337:342	arg1	O-GlcNAcylated					434:447	O-GlcNAcylated	434:447	O-GlcNAcylated	434:447	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	2	79	from	retina	337:342	arg1	repressor					366:374	the repressor	362:374	the repressor of mRNA translation	362:394	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	1	80	theme	Ser/Thr	250:256	arg1	residues					258:265	Ser/Thr residues	250:265	Ser/Thr residues of proteins	250:277	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	1	80	theme	Ser/Thr	250:256	arg1	proteins					270:277	proteins	270:277	proteins	270:277	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	5	81	theme	gene	837:840	arg1	expression					842:851	retinal gene expression	829:851	retinal gene expression	829:851	Here, using ribosome profiling, we evaluated the effect of enhanced O-GlcNAcylation on retinal gene expression.
30733333	12	82	theme	oxidative	1987:1995	arg1	stress					1997:2002	oxidative stress	1987:2002	oxidative stress in the retina	1987:2016	These findings provide evidence for a mechanism whereby diabetes-induced O-GlcNAcylation promotes oxidative stress in the retina by altering the selection of mRNAs for translation.
30733333	1	83	link	O-linked	201:208	arg1	addition					210:217	O-linked addition	201:217	O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins	201:277	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	1	84	theme	diabetic	306:313	arg1	complications					315:327	diabetic complications	306:327	diabetic complications	306:327	Diabetes promotes the posttranslational modification of proteins by O-linked addition of GlcNAc (O-GlcNAcylation) to Ser/Thr residues of proteins and thereby contributes to diabetic complications.
30733333	5	85	theme	enhanced	801:808	arg1	O-GlcNAcylation					810:824	enhanced O-GlcNAcylation	801:824	enhanced O-GlcNAcylation	801:824	Here, using ribosome profiling, we evaluated the effect of enhanced O-GlcNAcylation on retinal gene expression.
30733333	4	86	theme	modification	717:728	arg1	unknown					733:739	unknown	733:739	unknown	733:739	However, the functional consequence of this modification is unknown.
30733333	4	86	theme	modification	717:728	arg1	consequence					697:707	the functional consequence	682:707	the functional consequence of this modification	682:728	However, the functional consequence of this modification is unknown.
30733333	7	87	theme	mRNAs	1143:1147	arg1	mRNAs					1143:1147	mRNAs	1143:1147	mRNAs	1143:1147	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	7	87	theme	mRNAs	1143:1147	arg1	%					1138:1138	less than 1%	1127:1138	less than 1% of mRNAs	1127:1147	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	11	88	theme	WT	1769:1770	arg1	mice					1772:1775	diabetic WT mice	1760:1775	diabetic WT mice	1760:1775	The retina of diabetic WT mice exhibited increased reactive oxygen species levels, an effect not observed in diabetic 4E-BP1/2-deficient mice.
30733333	12	89	theme	diabetes-induced	1945:1960	arg1	O-GlcNAcylation					1962:1976	diabetes-induced O-GlcNAcylation	1945:1976	diabetes-induced O-GlcNAcylation	1945:1976	These findings provide evidence for a mechanism whereby diabetes-induced O-GlcNAcylation promotes oxidative stress in the retina by altering the selection of mRNAs for translation.
30733333	10	90	from	cells	1710:1714	arg1	culture					1719:1725	culture	1719:1725	culture	1719:1725	O-GlcNAcylation enhanced cellular respiration and promoted mitochondrial superoxide levels in WT cells, and 4E-BP1/2 deletion prevented O-GlcNAcylation-induced mitochondrial superoxide in cells in culture and in the retina.
30733333	2	91	theme	diabetic	347:354	arg1	mice					356:359	diabetic mice	347:359	diabetic mice	347:359	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	9	92	theme	inhibition	1397:1406	arg1	effect					1375:1380	the effect	1371:1380	the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2),	1371:1498	In the retina, the effect of O-GlcNAcase inhibition on translation of specific mitochondrial proteins, including superoxide dismutase 2 (SOD2), depended on 4E-BP1/2.
30733333	7	93	dep	mRNAs	1093:1097	arg1	i.e.					1088:1091	i.e.	1088:1091	i.e.	1088:1091	The principal effect of TMG on retinal gene expression was observed in ribosome-associated mRNAs (i.e. mRNAs undergoing translation), as less than 1% of mRNAs exhibited changes in abundance.
30733333	2	94	theme	mRNA	379:382	arg1	translation					384:394	mRNA translation	379:394	mRNA translation	379:394	In the retina of diabetic mice, the repressor of mRNA translation, eIF4E-binding protein 1 (4E-BP1), is O-GlcNAcylated, and sequestration of the cap-binding protein eukaryotic translation initiation factor (eIF4E) is enhanced.
30733333	6	95	theme	protein	965:971	arg1	O-GlcNAcylation					973:987	enhanced retinal protein O-GlcNAcylation	948:987	enhanced retinal protein O-GlcNAcylation	948:987	Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation.
31872598	2	0	from	effect	409:414	arg1	pressure					469:476	blood pressure	463:476	blood pressure	463:476	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	0	from	effect	409:414	arg1	DOE					455:457	DOE	455:457	DOE	455:457	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	0	from	effect	409:414	arg1	Glu					478:480	Glu	478:480	Glu	478:480	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	0	from	effect	409:414	arg1	officinale					443:452	D. officinale	440:452	D. officinale( DOE)	440:458	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	0	from	effect	409:414	arg1	profile					492:498	lipid profile	486:498	lipid profile	486:498	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	6	1	theme	effective	1215:1223	arg1	fractions					1225:1233	the most effective fractions	1206:1233	the most effective fractions	1206:1233	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	14	2	theme	D.	2269:2270	arg1	officinale					2272:2281	D. officinale	2269:2281	D. officinale	2269:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	4	3	theme	lipid	842:846	arg1	profile					848:854	lipid profile	842:854	lipid profile	842:854	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	13	4	contain	has	2088:2090	arg1	extract					2062:2068	Ethanol extract	2054:2068	Ethanol extract from D.officinale	2054:2086	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	13	4	contain	has	2088:2090	arg2	effect					2104:2109	an positive effect	2092:2109	an positive effect	2092:2109	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	6	5	theme	index	1117:1121	arg1	changes					1144:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	3	6	theme	high-fat	695:702	arg1	diet					704:707	high-fat diet	695:707	high-fat diet	695:707	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	14	7	theme	extraction	2253:2262	arg1	fraction					2233:2240	the effective fraction	2219:2240	the effective fraction of alcohol extraction from D. officinale	2219:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	14	7	theme	extraction	2253:2262	arg1	fraction					2206:2213	Medium polarity fraction	2190:2213	Medium polarity fraction	2190:2213	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	11	8	theme	aortas	1878:1883	arg1	deposition					1864:1873	less collagen deposition	1850:1873	less collagen deposition of aortas by Masson's trichrome staining	1850:1914	The level of MDA in serum was down-regulated,while GSH-Px and T-AOC were up-regulated obviously after 12 weeks.And the blood viscosity also obviously decreased,with less collagen deposition of aortas by Masson's trichrome staining.
31872598	1	9	theme	D.	280:281	arg1	DOP					295:297	DOP	295:297	DOP	295:297	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	1	9	theme	D.	280:281	arg1	officinale					283:292	D. officinale	280:292	D. officinale( DOP)	280:298	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	2	10	theme	effective	605:613	arg1	fractions					615:623	effective fractions	605:623	effective fractions from DOE	605:632	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	10	11	theme	model	1606:1610	arg1	rats					1612:1615	model rats	1606:1615	model rats	1606:1615	SBP,TG,Glu,UA of model rats were decreased significantly after 4 weeks administration with NBF.
31872598	14	12	theme	flavone	2318:2324	arg1	C-glycosides					2326:2337	flavone C-glycosides	2318:2337	flavone C-glycosides	2318:2337	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	13	13	from	hypertension	2126:2137	arg1	hypertension					2176:2187	metabolic hypertension	2166:2187	metabolic hypertension	2166:2187	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	11	14	theme	trichrome	1897:1905	arg1	staining					1907:1914	Masson's trichrome staining	1888:1914	Masson's trichrome staining	1888:1914	The level of MDA in serum was down-regulated,while GSH-Px and T-AOC were up-regulated obviously after 12 weeks.And the blood viscosity also obviously decreased,with less collagen deposition of aortas by Masson's trichrome staining.
31872598	11	15	from	level	1689:1693	arg1	serum					1705:1709	serum	1705:1709	serum	1705:1709	The level of MDA in serum was down-regulated,while GSH-Px and T-AOC were up-regulated obviously after 12 weeks.And the blood viscosity also obviously decreased,with less collagen deposition of aortas by Masson's trichrome staining.
31872598	6	16	theme	lipid	1080:1084	arg1	profile					1086:1092	lipid profile	1080:1092	lipid profile	1080:1092	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	12	17	theme	flavone	1956:1962	arg1	C-glycosides					1964:1975	flavone C-glycosides	1956:1975	flavone C-glycosides	1956:1975	NBF was mainly composed of phenols and flavone C-glycosides,whose aglycone was apigenin,and monosaccharide was connected to C-6 and C-8.
31872598	0	18	theme	comprehensive	119:131	arg1	dietary					133:139	comprehensive dietary	119:139	comprehensive dietary	119:139	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	13	19	theme	metabolic	2166:2174	arg1	hypertension					2176:2187	metabolic hypertension	2166:2187	metabolic hypertension	2166:2187	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	2	20	theme	metabolic	503:511	arg1	rats					526:529	metabolic hypertensive rats	503:529	metabolic hypertensive rats induced by comprehensive dietary factors	503:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	8	21	theme	models	1372:1377	arg1	Glu					1365:1367	Glu	1365:1367	Glu	1365:1367	The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically.
31872598	8	21	theme	models	1372:1377	arg1	SBP					1357:1359	SBP	1357:1359	SBP	1357:1359	The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically.
31872598	2	22	theme	dietary	556:562	arg1	factors					564:570	comprehensive dietary factors	542:570	comprehensive dietary factors	542:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	23	from	pressure	469:476	arg1	rats					526:529	metabolic hypertensive rats	503:529	metabolic hypertensive rats induced by comprehensive dietary factors	503:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	5	24	theme	different	990:998	arg1	solvents					1007:1014	three different common solvents	984:1014	three different common solvents according to the polarity	984:1040	Furthermore,DOE was separated with three different common solvents according to the polarity.
31872598	2	25	from	Glu	478:480	arg1	rats					526:529	metabolic hypertensive rats	503:529	metabolic hypertensive rats induced by comprehensive dietary factors	503:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	3	26	theme	DOE	768:770	arg1	effect					758:763	the effect	754:763	the effect of DOE on hypertension and other metabolic disorders	754:816	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	8	27	dep	SBP	1357:1359	arg1	The					1353:1355	The	1353:1355	The	1353:1355	The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically.
31872598	6	28	theme	aortas	1127:1132	arg1	changes					1144:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	14	29	theme	Medium	2190:2195	arg1	fraction					2233:2240	the effective fraction	2219:2240	the effective fraction of alcohol extraction from D. officinale	2219:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	14	29	theme	Medium	2190:2195	arg1	fraction					2206:2213	Medium polarity fraction	2190:2213	Medium polarity fraction	2190:2213	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	0	30	theme	Dendrobium	55:64	arg1	officinale					66:75	Dendrobium officinale	55:75	Dendrobium officinale	55:75	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	2	31	theme	blood	463:467	arg1	pressure					469:476	blood pressure	463:476	blood pressure	463:476	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	3	32	theme	other	792:796	arg1	disorders					808:816	other metabolic disorders	792:816	other metabolic disorders	792:816	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	2	33	from	profile	492:498	arg1	rats					526:529	metabolic hypertensive rats	503:529	metabolic hypertensive rats induced by comprehensive dietary factors	503:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	1	34	theme	Dendrobium	163:172	arg1	officinale					174:183	Dendrobium officinale	163:183	Dendrobium officinale	163:183	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	0	35	from	[Effects	0:7	arg1	rats					103:106	metabolic hypertensive rats	80:106	metabolic hypertensive rats	80:106	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	0	35	from	[Effects	0:7	arg1	officinale					66:75	Dendrobium officinale	55:75	Dendrobium officinale	55:75	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	0	36	theme	hypertensive	90:101	arg1	rats					103:106	metabolic hypertensive rats	80:106	metabolic hypertensive rats	80:106	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	1	37	theme	main	349:352	arg1	substances					364:373	the main effective substances	345:373	the main effective substances	345:373	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	2	38	from	officinale	443:452	arg1	effect					409:414	the effect	405:414	the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors	405:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	38	from	officinale	443:452	arg1	extract					427:433	ethanol extract	419:433	ethanol extract from D. officinale( DOE)	419:458	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	39	theme	fractions	615:623	arg1	composition					590:600	the composition	586:600	the composition of effective fractions from DOE	586:632	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	4	40	from	differences	895:905	arg1	hypertension					935:946	metabolic hypertension	925:946	metabolic hypertension	925:946	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	1	41	theme	substances	364:373	arg1	polysaccharides					261:275	polysaccharides	261:275	polysaccharides of D. officinale( DOP)	261:298	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	1	41	theme	substances	364:373	arg1	substances					364:373	the main effective substances	345:373	the main effective substances	345:373	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	1	41	theme	substances	364:373	arg1	one					338:340	one	338:340	one	338:340	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	0	42	theme	ethanol	34:40	arg1	extract					42:48	ethanol extract	34:48	ethanol extract from Dendrobium officinale	34:75	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	2	43	theme	D.	440:441	arg1	DOE					455:457	DOE	455:457	DOE	455:457	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	43	theme	D.	440:441	arg1	officinale					443:452	D. officinale	440:452	D. officinale( DOE)	440:458	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	1	44	theme	officinale	283:292	arg1	polysaccharides					261:275	polysaccharides	261:275	polysaccharides of D. officinale( DOP)	261:298	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	1	44	theme	officinale	283:292	arg1	substances					364:373	the main effective substances	345:373	the main effective substances	345:373	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	1	44	theme	officinale	283:292	arg1	one					338:340	one	338:340	one	338:340	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	2	45	theme	extract	427:433	arg1	effect					409:414	the effect	405:414	the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors	405:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	0	46	theme	active	13:18	arg1	substances					20:29	active substances	13:29	active substances	13:29	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	11	47	theme	collagen	1855:1862	arg1	deposition					1864:1873	less collagen deposition	1850:1873	less collagen deposition of aortas by Masson's trichrome staining	1850:1914	The level of MDA in serum was down-regulated,while GSH-Px and T-AOC were up-regulated obviously after 12 weeks.And the blood viscosity also obviously decreased,with less collagen deposition of aortas by Masson's trichrome staining.
31872598	13	48	theme	positive	2095:2102	arg1	effect					2104:2109	an positive effect	2092:2109	an positive effect	2092:2109	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	3	49	from	effect	758:763	arg1	disorders					808:816	other metabolic disorders	792:816	other metabolic disorders	792:816	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	3	49	from	effect	758:763	arg1	hypertension					775:786	hypertension	775:786	hypertension	775:786	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	0	50	theme	extract	42:48	arg1	[Effects					0:7	[Effects	0:7	[Effects	0:7	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	0	50	theme	extract	42:48	arg1	substances					20:29	active substances	13:29	active substances	13:29	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	13	51	theme	Ethanol	2054:2060	arg1	extract					2062:2068	Ethanol extract	2054:2068	Ethanol extract from D.officinale	2054:2086	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	0	52	from	substances	20:29	arg1	rats					103:106	metabolic hypertensive rats	80:106	metabolic hypertensive rats	80:106	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	0	52	from	substances	20:29	arg1	officinale					66:75	Dendrobium officinale	55:75	Dendrobium officinale	55:75	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	3	53	theme	metabolic	637:645	arg1	model					660:664	A metabolic hypertension model	635:664	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking	635:728	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	6	54	theme	blood	1054:1058	arg1	pressure					1060:1067	blood pressure	1054:1067	blood pressure	1054:1067	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	6	55	theme	fractions	1225:1233	arg1	effects					1195:1201	the comprehensive effects	1177:1201	the comprehensive effects of the most effective fractions on metabolic hypertension	1177:1259	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	9	56	theme	named	1566:1570	arg1	NAF					1572:1574	NAF	1572:1574	NAF	1572:1574	The DOE was separated with ether,n-butanol respectively and named NAF,NBF and NCF.
31872598	3	57	theme	rat	669:671	arg1	model					660:664	A metabolic hypertension model	635:664	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking	635:728	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	6	58	theme	oxidative	1107:1115	arg1	index					1117:1121	oxidative index	1107:1121	oxidative index	1107:1121	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	14	59	theme	alcohol	2245:2251	arg1	extraction					2253:2262	alcohol extraction	2245:2262	alcohol extraction from D. officinale	2245:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	10	60	theme	rats	1612:1615	arg1	TG					1593:1594	TG	1593:1594	TG	1593:1594	SBP,TG,Glu,UA of model rats were decreased significantly after 4 weeks administration with NBF.
31872598	10	60	theme	rats	1612:1615	arg1	SBP					1589:1591	SBP	1589:1591	SBP	1589:1591	SBP,TG,Glu,UA of model rats were decreased significantly after 4 weeks administration with NBF.
31872598	10	60	theme	rats	1612:1615	arg1	UA					1600:1601	UA	1600:1601	UA	1600:1601	SBP,TG,Glu,UA of model rats were decreased significantly after 4 weeks administration with NBF.
31872598	10	60	theme	rats	1612:1615	arg1	Glu					1596:1598	Glu	1596:1598	Glu	1596:1598	SBP,TG,Glu,UA of model rats were decreased significantly after 4 weeks administration with NBF.
31872598	1	61	theme	officinale	174:183	arg1	studies					152:158	Previous studies	143:158	Previous studies of Dendrobium officinale on anti-hypertension effect	143:211	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	6	62	theme	hemorheology	1094:1105	arg1	changes					1144:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	6	63	theme	comprehensive	1181:1193	arg1	effects					1195:1201	the comprehensive effects	1177:1201	the comprehensive effects of the most effective fractions on metabolic hypertension	1177:1259	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	13	64	from	disorders	2153:2161	arg1	hypertension					2176:2187	metabolic hypertension	2166:2187	metabolic hypertension	2166:2187	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	10	65	theme	weeks	1654:1658	arg1	administration					1660:1673	4 weeks administration	1652:1673	4 weeks administration	1652:1673	SBP,TG,Glu,UA of model rats were decreased significantly after 4 weeks administration with NBF.
31872598	1	66	theme	anti-hypertension	188:204	arg1	effect					206:211	anti-hypertension effect	188:211	anti-hypertension effect	188:211	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	4	67	theme	Blood	819:823	arg1	pressure					825:832	Blood pressure	819:832	Blood pressure	819:832	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	14	68	theme	effective	2223:2231	arg1	fraction					2233:2240	the effective fraction	2219:2240	the effective fraction of alcohol extraction from D. officinale	2219:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	14	68	theme	effective	2223:2231	arg1	fraction					2206:2213	Medium polarity fraction	2190:2213	Medium polarity fraction	2190:2213	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	2	69	theme	hypertensive	513:524	arg1	rats					526:529	metabolic hypertensive rats	503:529	metabolic hypertensive rats induced by comprehensive dietary factors	503:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	7	70	theme	fraction	1343:1350	arg1	components					1310:1319	the components	1306:1319	the components of the most effective fraction	1306:1350	Finally,HPLC-DAD-MS was adopted to identify the components of the most effective fraction.
31872598	3	71	theme	alcohol	713:719	arg1	drinking					721:728	alcohol drinking	713:728	alcohol drinking	713:728	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	4	72	from	features	882:889	arg1	hypertension					935:946	metabolic hypertension	925:946	metabolic hypertension	925:946	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	0	73	from	officinale	66:75	arg1	[Effects					0:7	[Effects	0:7	[Effects	0:7	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	0	73	from	officinale	66:75	arg1	substances					20:29	active substances	13:29	active substances	13:29	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	0	73	from	officinale	66:75	arg1	extract					42:48	ethanol extract	34:48	ethanol extract from Dendrobium officinale	34:75	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	11	74	theme	MDA	1698:1700	arg1	level					1689:1693	The level	1685:1693	The level of MDA in serum	1685:1709	The level of MDA in serum was down-regulated,while GSH-Px and T-AOC were up-regulated obviously after 12 weeks.And the blood viscosity also obviously decreased,with less collagen deposition of aortas by Masson's trichrome staining.
31872598	11	75	theme	blood	1804:1808	arg1	viscosity					1810:1818	the blood viscosity	1800:1818	the blood viscosity	1800:1818	The level of MDA in serum was down-regulated,while GSH-Px and T-AOC were up-regulated obviously after 12 weeks.And the blood viscosity also obviously decreased,with less collagen deposition of aortas by Masson's trichrome staining.
31872598	2	76	theme	comprehensive	542:554	arg1	factors					564:570	comprehensive dietary factors	542:570	comprehensive dietary factors	542:570	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	6	77	from	effects	1195:1201	arg1	hypertension					1248:1259	metabolic hypertension	1238:1259	metabolic hypertension	1238:1259	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	6	78	theme	metabolic	1238:1246	arg1	hypertension					1248:1259	metabolic hypertension	1238:1259	metabolic hypertension	1238:1259	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	5	79	theme	common	1000:1005	arg1	solvents					1007:1014	three different common solvents	984:1014	three different common solvents according to the polarity	984:1040	Furthermore,DOE was separated with three different common solvents according to the polarity.
31872598	13	80	theme	metabolic	2143:2151	arg1	disorders					2153:2161	metabolic disorders	2143:2161	metabolic disorders	2143:2161	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	7	81	theme	effective	1333:1341	arg1	fraction					1343:1350	the most effective fraction	1324:1350	the most effective fraction	1324:1350	Finally,HPLC-DAD-MS was adopted to identify the components of the most effective fraction.
31872598	8	82	theme	DOE	1432:1434	arg1	administration					1414:1427	administration	1414:1427	administration of DOE and DOP	1414:1442	The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically.
31872598	6	83	theme	structure	1134:1142	arg1	changes					1144:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	hemorheology,oxidative index and aortas structure changes	1094:1150	Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension.
31872598	2	84	from	DOE	630:632	arg1	composition					590:600	the composition	586:600	the composition of effective fractions from DOE	586:632	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	2	84	from	DOE	630:632	arg1	fractions					615:623	effective fractions	605:623	effective fractions from DOE	605:632	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	14	85	theme	polarity	2197:2204	arg1	fraction					2233:2240	the effective fraction	2219:2240	the effective fraction of alcohol extraction from D. officinale	2219:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	14	85	theme	polarity	2197:2204	arg1	fraction					2206:2213	Medium polarity fraction	2190:2213	Medium polarity fraction	2190:2213	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	1	86	theme	Previous	143:150	arg1	studies					152:158	Previous studies	143:158	Previous studies of Dendrobium officinale on anti-hypertension effect	143:211	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	4	87	theme	DOP	918:920	arg1	differences					895:905	differences	895:905	differences	895:905	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	4	87	theme	DOP	918:920	arg1	features					882:889	features	882:889	features	882:889	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	8	88	theme	DOP	1440:1442	arg1	administration					1414:1427	administration	1414:1427	administration of DOE and DOP	1414:1442	The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically.
31872598	4	89	dep	features	882:889	arg1	the					878:880	the	878:880	the	878:880	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	0	90	theme	metabolic	80:88	arg1	rats					103:106	metabolic hypertensive rats	80:106	metabolic hypertensive rats	80:106	[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].
31872598	4	91	theme	metabolic	925:933	arg1	hypertension					935:946	metabolic hypertension	925:946	metabolic hypertension	925:946	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	3	92	theme	metabolic	798:806	arg1	disorders					808:816	other metabolic disorders	792:816	other metabolic disorders	792:816	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	14	93	from	fraction	2233:2240	arg1	officinale					2272:2281	D. officinale	2269:2281	D. officinale	2269:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	2	94	theme	lipid	486:490	arg1	profile					492:498	lipid profile	486:498	lipid profile	486:498	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	1	95	theme	effective	354:362	arg1	substances					364:373	the main effective substances	345:373	the main effective substances	345:373	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	1	96	from	studies	152:158	arg1	effect					206:211	anti-hypertension effect	188:211	anti-hypertension effect	188:211	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31872598	4	97	theme	DOE	910:912	arg1	differences					895:905	differences	895:905	differences	895:905	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	4	97	theme	DOE	910:912	arg1	features					882:889	features	882:889	features	882:889	Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension.
31872598	8	98	theme	DOE	1468:1470	arg1	groups					1472:1477	DOE groups	1468:1477	DOE groups	1468:1477	The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically.
31872598	13	99	from	D.officinale	2075:2086	arg1	extract					2062:2068	Ethanol extract	2054:2068	Ethanol extract from D.officinale	2054:2086	Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension.
31872598	2	100	theme	ethanol	419:425	arg1	extract					427:433	ethanol extract	419:433	ethanol extract from D. officinale( DOE)	419:458	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	8	101	from	TG	1462:1463	arg1	groups					1472:1477	DOE groups	1468:1477	DOE groups	1468:1477	The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically.
31872598	2	102	from	composition	590:600	arg1	DOE					630:632	DOE	630:632	DOE	630:632	This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE.
31872598	3	103	theme	hypertension	647:658	arg1	model					660:664	A metabolic hypertension model	635:664	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking	635:728	A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders.
31872598	14	104	from	officinale	2272:2281	arg1	fraction					2233:2240	the effective fraction	2219:2240	the effective fraction of alcohol extraction from D. officinale	2219:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	14	104	from	officinale	2272:2281	arg1	extraction					2253:2262	alcohol extraction	2245:2262	alcohol extraction from D. officinale	2245:2281	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	14	104	from	officinale	2272:2281	arg1	fraction					2206:2213	Medium polarity fraction	2190:2213	Medium polarity fraction	2190:2213	Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.
31872598	1	105	theme	blood	240:244	arg1	pressure					246:253	the blood pressure	236:253	the blood pressure	236:253	Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances.
31152877	3	0	theme	enzyme	630:635	arg1	protocol					637:644	the best enzyme protocol	621:644	the best enzyme protocol	621:644	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	2	1	theme	photosensitizer	346:360	arg1	penetration					327:337	the penetration	323:337	the penetration of the photosensitizer	323:360	However, microorganisms in biofilms are less susceptible to aPDT than planktonic cultures, possibly because the matrix limits the penetration of the photosensitizer.
31152877	3	2	theme	confocal	726:733	arg1	microscope					735:744	confocal microscope	726:744	confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation	726:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	0	3	theme	albicans	78:85	arg1	biofilms					87:94	Candida albicans biofilms	70:94	Candida albicans biofilms	70:94	DNase increases the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms.
31152877	5	4	theme	best	1009:1012	arg1	outcomes					1014:1021	the best outcomes	1005:1021	the best outcomes	1005:1021	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	8	5	theme	biofilm	1539:1545	arg1	layers					1547:1552	deeper biofilm layers	1532:1552	deeper biofilm layers	1532:1552	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	5	6	theme	soluble	1078:1084	arg1	proteins					1086:1093	soluble proteins	1078:1093	soluble proteins from the matrix of both strains	1078:1125	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	4	7	theme	CaS	847:849	arg1	biofilms					867:874	CaS and CaR 48h-old biofilms	847:874	CaS and CaR 48h-old biofilms	847:874	CaS and CaR 48h-old biofilms were incubated with the hydrolytic enzymes (5 min) and evaluated by cell viability, biomass, and matrix components.
31152877	8	8	theme	viability	1633:1641	arg1	reduction					1611:1619	a significant reduction	1597:1619	a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047)	1597:1682	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	3	9	dep	fluconazole-susceptible	440:462	arg1	C.					500:501	C.	500:501	C.	500:501	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	4	10	theme	cell	944:947	arg1	viability					949:957	cell viability	944:957	cell viability	944:957	CaS and CaR 48h-old biofilms were incubated with the hydrolytic enzymes (5 min) and evaluated by cell viability, biomass, and matrix components.
31152877	8	11	theme	aPDT	1563:1566	arg1	effect					1568:1573	the aPDT effect	1559:1573	the aPDT effect	1559:1573	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	9	12	theme	aPDT	1824:1827	arg1	effectiveness					1796:1808	the effectiveness	1792:1808	the effectiveness of subsequent aPDT	1792:1827	DNase affected the matrix composition improving the penetration of the photosensitizer, thereby, improving the effectiveness of subsequent aPDT.
31152877	4	13	theme	CaR	855:857	arg1	biofilms					867:874	CaS and CaR 48h-old biofilms	847:874	CaS and CaR 48h-old biofilms	847:874	CaS and CaR 48h-old biofilms were incubated with the hydrolytic enzymes (5 min) and evaluated by cell viability, biomass, and matrix components.
31152877	2	14	theme	planktonic	267:276	arg1	cultures					278:285	planktonic cultures	267:285	planktonic cultures	267:285	However, microorganisms in biofilms are less susceptible to aPDT than planktonic cultures, possibly because the matrix limits the penetration of the photosensitizer.
31152877	2	15	from	microorganisms	206:219	arg1	biofilms					224:231	biofilms	224:231	biofilms	224:231	However, microorganisms in biofilms are less susceptible to aPDT than planktonic cultures, possibly because the matrix limits the penetration of the photosensitizer.
31152877	4	16	theme	hydrolytic	900:909	arg1	5 min					920:924	5 min	920:924	5 min	920:924	CaS and CaR 48h-old biofilms were incubated with the hydrolytic enzymes (5 min) and evaluated by cell viability, biomass, and matrix components.
31152877	4	16	theme	hydrolytic	900:909	arg1	enzymes					911:917	the hydrolytic enzymes	896:917	the hydrolytic enzymes (5 min)	896:925	CaS and CaR 48h-old biofilms were incubated with the hydrolytic enzymes (5 min) and evaluated by cell viability, biomass, and matrix components.
31152877	8	17	theme	eDNA	1659:1662	arg1	p ≤ 0.047					1673:1681	p ≤ 0.047	1673:1681	p ≤ 0.047	1673:1681	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	8	17	theme	eDNA	1659:1662	arg1	amounts					1664:1670	eDNA amounts	1659:1670	eDNA amounts (p ≤ 0.047)	1659:1682	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	3	18	theme	biofilm	409:415	arg1	components					424:433	biofilm matrix components	409:433	biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination	409:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	9	19	theme	photosensitizer	1756:1770	arg1	penetration					1737:1747	the penetration	1733:1747	the penetration of the photosensitizer	1733:1770	DNase affected the matrix composition improving the penetration of the photosensitizer, thereby, improving the effectiveness of subsequent aPDT.
31152877	8	20	with	Pre-treatment	1478:1490	arg1	DNase					1497:1501	DNase	1497:1501	DNase	1497:1501	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	6	21	theme	LED	1306:1308	arg1	light					1310:1314	LED light	1306:1314	LED light (660 nm, 50 J/cm²)	1306:1333	Subsequently, 48h-old biofilms were incubated with DNase for 5 min, followed by incubation with PDZ for 20 min and exposure to LED light (660 nm, 50 J/cm²).
31152877	9	22	dep	affected	1691:1698	arg1	improving					1782:1790	improving	1782:1790	improving the effectiveness of subsequent aPDT	1782:1827	DNase affected the matrix composition improving the penetration of the photosensitizer, thereby, improving the effectiveness of subsequent aPDT.
31152877	1	23	theme	Antimicrobial	97:109	arg1	means					162:166	a means	160:166	a means to treat Candida infections	160:194	Antimicrobial Photodynamic Therapy (aPDT) has been proposed as a means to treat Candida infections.
31152877	1	23	theme	Antimicrobial	97:109	arg1	aPDT					133:136	aPDT	133:136	aPDT	133:136	Antimicrobial Photodynamic Therapy (aPDT) has been proposed as a means to treat Candida infections.
31152877	1	23	theme	Antimicrobial	97:109	arg1	Therapy					124:130	Antimicrobial Photodynamic Therapy	97:130	Antimicrobial Photodynamic Therapy (aPDT)	97:137	Antimicrobial Photodynamic Therapy (aPDT) has been proposed as a means to treat Candida infections.
31152877	1	24	theme	Candida	177:183	arg1	infections					185:194	Candida infections	177:194	Candida infections	177:194	Antimicrobial Photodynamic Therapy (aPDT) has been proposed as a means to treat Candida infections.
31152877	8	25	theme	amounts	1664:1670	arg1	reduction					1611:1619	a significant reduction	1597:1619	a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047)	1597:1682	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	1	26	theme	Photodynamic	111:122	arg1	means					162:166	a means	160:166	a means to treat Candida infections	160:194	Antimicrobial Photodynamic Therapy (aPDT) has been proposed as a means to treat Candida infections.
31152877	1	26	theme	Photodynamic	111:122	arg1	aPDT					133:136	aPDT	133:136	aPDT	133:136	Antimicrobial Photodynamic Therapy (aPDT) has been proposed as a means to treat Candida infections.
31152877	1	26	theme	Photodynamic	111:122	arg1	Therapy					124:130	Antimicrobial Photodynamic Therapy	97:130	Antimicrobial Photodynamic Therapy (aPDT)	97:137	Antimicrobial Photodynamic Therapy (aPDT) has been proposed as a means to treat Candida infections.
31152877	3	27	theme	incubation	835:844	arg1	periods					824:830	different periods	814:830	different periods of incubation	814:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	28	theme	strains	517:523	arg1	components					424:433	biofilm matrix components	409:433	biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination	409:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	5	29	theme	CaR	1167:1169	arg1	matrix					1171:1176	CaR matrix	1167:1176	CaR matrix	1167:1176	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	3	30	theme	different	814:822	arg1	periods					824:830	different periods	814:830	different periods of incubation	814:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	5	31	from	matrix	1171:1176	arg1	proteins					1086:1093	soluble proteins	1078:1093	soluble proteins from the matrix of both strains	1078:1125	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	5	31	from	matrix	1171:1176	arg1	eDNA					1068:1071	eDNA	1068:1071	eDNA	1068:1071	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	5	31	from	matrix	1171:1176	arg1	polysaccharides					1146:1160	water-soluble polysaccharides	1132:1160	water-soluble polysaccharides from CaR matrix	1132:1176	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	5	31	from	matrix	1171:1176	arg1	DNA					1063:1065	extracellular DNA	1049:1065	extracellular DNA (eDNA)	1049:1072	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	0	32	theme	antimicrobial	32:44	arg1	therapy					59:65	antimicrobial photodynamic therapy	32:65	antimicrobial photodynamic therapy	32:65	DNase increases the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms.
31152877	9	33	theme	matrix	1704:1709	arg1	composition					1711:1721	the matrix composition	1700:1721	the matrix composition improving the penetration of the photosensitizer	1700:1770	DNase affected the matrix composition improving the penetration of the photosensitizer, thereby, improving the effectiveness of subsequent aPDT.
31152877	3	34	theme	hydrolytic	535:544	arg1	enzymes					546:552	the hydrolytic enzymes	531:552	the hydrolytic enzymes β-glucanase and DNase individually or in combination	531:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	34	theme	hydrolytic	535:544	arg1	DNase					570:574	DNase	570:574	DNase individually or in combination	570:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	34	theme	hydrolytic	535:544	arg1	β-glucanase					554:564	β-glucanase	554:564	β-glucanase	554:564	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	35	dep	enzymes	546:552	arg1	enzymes					546:552	the hydrolytic enzymes	531:552	the hydrolytic enzymes β-glucanase and DNase individually or in combination	531:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	35	dep	enzymes	546:552	arg1	DNase					570:574	DNase	570:574	DNase individually or in combination	570:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	35	dep	enzymes	546:552	arg1	β-glucanase					554:564	β-glucanase	554:564	β-glucanase	554:564	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	36	theme	matrix	417:422	arg1	components					424:433	biofilm matrix components	409:433	biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination	409:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	37	from	microscope	735:744	arg1	biofilms					772:779	biofilms	772:779	biofilms pre-treated or not with DNase at different periods of incubation	772:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	38	from	periods	824:830	arg1	DNase					805:809	DNase	805:809	DNase at different periods of incubation	805:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	0	39	theme	therapy	59:65	arg1	efficacy					20:27	the efficacy	16:27	the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms	16:94	DNase increases the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms.
31152877	5	40	theme	water-soluble	1132:1144	arg1	polysaccharides					1146:1160	water-soluble polysaccharides	1132:1160	water-soluble polysaccharides from CaR matrix	1132:1176	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	6	41	theme	48h-old	1193:1199	arg1	biofilms					1201:1208	48h-old biofilms	1193:1208	48h-old biofilms	1193:1208	Subsequently, 48h-old biofilms were incubated with DNase for 5 min, followed by incubation with PDZ for 20 min and exposure to LED light (660 nm, 50 J/cm²).
31152877	3	42	dep	target	402:407	arg1	2					609:609	2	609:609	2	609:609	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	42	dep	target	402:407	arg1	apply					615:619	apply	615:619	to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ)	612:703	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	42	dep	target	402:407	arg1	3					707:707	3	707:707	3	707:707	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	42	dep	target	402:407	arg1	verify					713:718	verify	713:718	to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation	710:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	42	dep	target	402:407	arg1	1					396:396	1	396:396	1	396:396	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	0	43	theme	photodynamic	46:57	arg1	therapy					59:65	antimicrobial photodynamic therapy	32:65	antimicrobial photodynamic therapy	32:65	DNase increases the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms.
31152877	3	44	theme	best	625:628	arg1	protocol					637:644	the best enzyme protocol	621:644	the best enzyme protocol	621:644	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	8	45	theme	significant	1599:1609	arg1	reduction					1611:1619	a significant reduction	1597:1619	a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047)	1597:1682	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	5	46	theme	extracellular	1049:1061	arg1	eDNA					1068:1071	eDNA	1068:1071	eDNA	1068:1071	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	5	46	theme	extracellular	1049:1061	arg1	DNA					1063:1065	extracellular DNA	1049:1065	extracellular DNA (eDNA)	1049:1072	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	6	47	dep	light	1310:1314	arg1	50 J/cm²					1325:1332	50 J/cm²	1325:1332	50 J/cm²	1325:1332	Subsequently, 48h-old biofilms were incubated with DNase for 5 min, followed by incubation with PDZ for 20 min and exposure to LED light (660 nm, 50 J/cm²).
31152877	6	47	dep	light	1310:1314	arg1	660 nm					1317:1322	660 nm	1317:1322	660 nm	1317:1322	Subsequently, 48h-old biofilms were incubated with DNase for 5 min, followed by incubation with PDZ for 20 min and exposure to LED light (660 nm, 50 J/cm²).
31152877	6	48	with	incubation	1259:1268	arg1	PDZ					1275:1277	PDZ	1275:1277	PDZ	1275:1277	Subsequently, 48h-old biofilms were incubated with DNase for 5 min, followed by incubation with PDZ for 20 min and exposure to LED light (660 nm, 50 J/cm²).
31152877	3	49	theme	fluconazole-susceptible	440:462	arg1	strains					517:523	a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains	438:523	a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination	438:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	50	theme	PDZ	765:767	arg1	penetration					750:760	the penetration	746:760	confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation	726:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	5	51	from	matrix	1104:1109	arg1	proteins					1086:1093	soluble proteins	1078:1093	soluble proteins from the matrix of both strains	1078:1125	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	5	51	from	matrix	1104:1109	arg1	eDNA					1068:1071	eDNA	1068:1071	eDNA	1068:1071	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	5	51	from	matrix	1104:1109	arg1	polysaccharides					1146:1160	water-soluble polysaccharides	1132:1160	water-soluble polysaccharides from CaR matrix	1132:1176	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	5	51	from	matrix	1104:1109	arg1	DNA					1063:1065	extracellular DNA	1049:1065	extracellular DNA (eDNA)	1049:1072	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	4	52	theme	matrix	973:978	arg1	components					980:989	matrix components	973:989	matrix components	973:989	CaS and CaR 48h-old biofilms were incubated with the hydrolytic enzymes (5 min) and evaluated by cell viability, biomass, and matrix components.
31152877	3	53	with	association	649:659	arg1	aPDT					666:669	aPDT	666:669	aPDT mediated by Photodithazine® (PDZ)	666:703	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	3	54	dep	C.	500:501	arg1	albicans					503:510	C. albicans	500:510	C. albicans	500:510	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	0	55	theme	Candida	70:76	arg1	albicans					78:85	Candida albicans	70:85	Candida albicans biofilms	70:94	DNase increases the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms.
31152877	3	56	dep	microscope	735:744	arg1	penetration					750:760	the penetration	746:760	confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation	726:844	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	8	57	theme	PDZ	1511:1513	arg1	penetration					1515:1525	PDZ penetration	1511:1525	PDZ penetration into deeper biofilm layers	1511:1552	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	3	58	theme	fluconazole-resistant	474:494	arg1	strains					517:523	a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains	438:523	a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination	438:605	Therefore, the goals here were: (1) to target biofilm matrix components of a fluconazole-susceptible (S) and a fluconazole-resistant (R) C. albicans (Ca) strains using the hydrolytic enzymes β-glucanase and DNase individually or in combination; (2) to apply the best enzyme protocol in association with aPDT mediated by Photodithazine® (PDZ); (3) to verify under confocal microscope the penetration of PDZ in biofilms pre-treated or not with DNase at different periods of incubation.
31152877	8	59	theme	deeper	1532:1537	arg1	layers					1547:1552	deeper biofilm layers	1532:1552	deeper biofilm layers	1532:1552	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	4	60	theme	48h-old	859:865	arg1	biofilms					867:874	CaS and CaR 48h-old biofilms	847:874	CaS and CaR 48h-old biofilms	847:874	CaS and CaR 48h-old biofilms were incubated with the hydrolytic enzymes (5 min) and evaluated by cell viability, biomass, and matrix components.
31152877	0	61	from	efficacy	20:27	arg1	biofilms					87:94	Candida albicans biofilms	70:94	Candida albicans biofilms	70:94	DNase increases the efficacy of antimicrobial photodynamic therapy on Candida albicans biofilms.
31152877	8	62	theme	cell	1628:1631	arg1	p = 0.000					1644:1652	p = 0.000	1644:1652	p = 0.000	1644:1652	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	8	62	theme	cell	1628:1631	arg1	viability					1633:1641	the cell viability	1624:1641	the cell viability (p = 0.000)	1624:1653	Pre-treatment with DNase allowed PDZ penetration into deeper biofilm layers, and the aPDT effect was enhanced, showing a significant reduction of the cell viability (p = 0.000) and eDNA amounts (p ≤ 0.047).
31152877	5	63	theme	strains	1119:1125	arg1	matrix					1104:1109	the matrix	1100:1109	the matrix of both strains	1100:1125	DNase showed the best outcomes by significantly reducing extracellular DNA (eDNA) and soluble proteins from the matrix of both strains; and water-soluble polysaccharides from CaR matrix.
31152877	9	64	theme	subsequent	1813:1822	arg1	aPDT					1824:1827	subsequent aPDT	1813:1827	subsequent aPDT	1813:1827	DNase affected the matrix composition improving the penetration of the photosensitizer, thereby, improving the effectiveness of subsequent aPDT.
30909470	0	0	theme	Microencapsulation	74:91	arg1	Efficiency					93:102	the Microencapsulation Efficiency	70:102	the Microencapsulation Efficiency	70:102	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	3	1	theme	Microencapsulated	339:355	arg1	systems					357:363	Microencapsulated systems	339:363	Microencapsulated systems	339:363	Microencapsulated systems were obtained by spray-drying a mild alkaline bixin dispersion with different encapsulating materials.
30909470	1	2	from	integument	179:188	arg1	present					164:170	present	164:170	present	164:170	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	1	3	theme	present	164:170	arg1	carotenoid					153:162	a hydrophobic carotenoid	139:162	a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana	139:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	1	3	theme	present	164:170	arg1	Bixin					130:134	Bixin	130:134	Bixin	130:134	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	5	4	with	possible	608:615	arg1	bixin					651:655	up to 10% bixin	641:655	up to 10% bixin counted on total solids	641:679	It was possible to dry dispersions with up to 10% bixin counted on total solids.
30909470	4	5	theme	integument	553:562	arg1	carbohydrates					532:544	native carbohydrates	525:544	native carbohydrates of the integument in addition to the main encapsulant	525:598	The encapsulation trials were performed with and without native carbohydrates of the integument in addition to the main encapsulant.
30909470	4	6	from	addition	567:574	arg1	carbohydrates					532:544	native carbohydrates	525:544	native carbohydrates of the integument in addition to the main encapsulant	525:598	The encapsulation trials were performed with and without native carbohydrates of the integument in addition to the main encapsulant.
30909470	1	7	from	present	164:170	arg1	integument					179:188	the integument	175:188	the integument of the seeds of Bixa orellana	175:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	11	8	theme	bixin	1393:1397	arg1	encapsulation					1376:1388	the encapsulation	1372:1388	the encapsulation of bixin in its native microcrystalline form, resulting in a multilayer structure after spray-drying	1372:1489	The native carbohydrates allowed the encapsulation of bixin in its native microcrystalline form, resulting in a multilayer structure after spray-drying.
30909470	2	9	theme	water	262:266	arg1	formulations					280:291	water dispersible formulations	262:291	water dispersible formulations	262:291	Microencapsulation was applied to obtain water dispersible formulations and protect the colorant against degradation.
30909470	8	10	theme	other	1114:1118	arg1	materials					1134:1142	other encapsulating materials	1114:1142	other encapsulating materials	1114:1142	The results show that the native carbohydrates enhance the encapsulation efficiency of other encapsulating materials.
30909470	6	11	theme	diffraction	863:873	arg1	analyses					875:882	diffraction analyses	863:882	diffraction analyses	863:882	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	11	12	theme	native	1406:1411	arg1	form					1430:1433	its native microcrystalline form	1402:1433	its native microcrystalline form	1402:1433	The native carbohydrates allowed the encapsulation of bixin in its native microcrystalline form, resulting in a multilayer structure after spray-drying.
30909470	3	13	theme	mild	397:400	arg1	dispersion					417:426	a mild alkaline bixin dispersion	395:426	a mild alkaline bixin dispersion with different encapsulating materials	395:465	Microencapsulated systems were obtained by spray-drying a mild alkaline bixin dispersion with different encapsulating materials.
30909470	12	14	theme	acidic	1559:1564	arg1	conditions					1574:1583	acidic aqueous conditions	1559:1583	acidic aqueous conditions	1559:1583	In addition, the colorant particles displayed dispersibility under acidic aqueous conditions suggesting that they are stabilized by the native carbohydrates after the microcapsules are dissolved.
30909470	4	15	from	integument	553:562	arg1	addition					567:574	addition	567:574	addition	567:574	The encapsulation trials were performed with and without native carbohydrates of the integument in addition to the main encapsulant.
30909470	7	16	from	differences	945:955	arg1	stability					1008:1016	physical stability	999:1016	physical stability	999:1016	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	7	16	from	differences	945:955	arg1	transparency					966:977	their transparency	960:977	their transparency	960:977	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	7	16	from	differences	945:955	arg1	pH					1021:1022	pH 3	1021:1024	pH 3	1021:1024	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	7	16	from	differences	945:955	arg1	spectra					987:993	UV-vis spectra	980:993	UV-vis spectra	980:993	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	9	17	theme	chemical	1149:1156	arg1	composition					1158:1168	The chemical composition	1145:1168	The chemical composition of this native carbohydrate fraction	1145:1205	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	8	18	theme	native	1053:1058	arg1	carbohydrates					1060:1072	the native carbohydrates	1049:1072	the native carbohydrates	1049:1072	The results show that the native carbohydrates enhance the encapsulation efficiency of other encapsulating materials.
30909470	4	19	theme	native	525:530	arg1	carbohydrates					532:544	native carbohydrates	525:544	native carbohydrates of the integument in addition to the main encapsulant	525:598	The encapsulation trials were performed with and without native carbohydrates of the integument in addition to the main encapsulant.
30909470	8	20	theme	materials	1134:1142	arg1	efficiency					1100:1109	the encapsulation efficiency	1082:1109	the encapsulation efficiency of other encapsulating materials	1082:1142	The results show that the native carbohydrates enhance the encapsulation efficiency of other encapsulating materials.
30909470	6	21	theme	laser	851:855	arg1	light					857:861	laser light	851:861	laser light	851:861	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	6	22	theme	UV-vis	741:746	arg1	spectroscopy					748:759	UV-vis spectroscopy	741:759	UV-vis spectroscopy	741:759	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	0	23	theme	Dispersion	108:117	arg1	Stability					119:127	Dispersion Stability	108:127	Dispersion Stability	108:127	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	0	24	from	Impact	36:41	arg1	Efficiency					93:102	the Microencapsulation Efficiency	70:102	the Microencapsulation Efficiency	70:102	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	0	24	from	Impact	36:41	arg1	Stability					119:127	Dispersion Stability	108:127	Dispersion Stability	108:127	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	8	25	theme	encapsulating	1120:1132	arg1	materials					1134:1142	other encapsulating materials	1114:1142	other encapsulating materials	1114:1142	The results show that the native carbohydrates enhance the encapsulation efficiency of other encapsulating materials.
30909470	5	26	theme	dry	620:622	arg1	dispersions					624:634	dry dispersions	620:634	dry dispersions	620:634	It was possible to dry dispersions with up to 10% bixin counted on total solids.
30909470	11	27	theme	multilayer	1451:1460	arg1	structure					1462:1470	a multilayer structure	1449:1470	a multilayer structure after spray-drying	1449:1489	The native carbohydrates allowed the encapsulation of bixin in its native microcrystalline form, resulting in a multilayer structure after spray-drying.
30909470	0	28	theme	Bixin	11:15	arg1	Microcapsules					17:29	Multilayer Bixin Microcapsules	0:29	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.	0:128	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	1	29	attach	present	164:170	arg2	carotenoid					153:162	a hydrophobic carotenoid	139:162	a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana	139:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	1	29	attach	present	164:170	arg1	integument					179:188	the integument	175:188	the integument of the seeds of Bixa orellana	175:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	1	29	attach	present	164:170	arg2	Bixin					130:134	Bixin	130:134	Bixin	130:134	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	4	30	from	carbohydrates	532:544	arg1	addition					567:574	addition	567:574	addition	567:574	The encapsulation trials were performed with and without native carbohydrates of the integument in addition to the main encapsulant.
30909470	6	31	dep	colorimetry	728:738	arg1	analyses					875:882	diffraction analyses	863:882	diffraction analyses	863:882	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	7	32	theme	aqueous	908:914	arg1	dispersibility					916:929	aqueous dispersibility	908:929	aqueous dispersibility	908:929	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	0	33	theme	Multilayer	0:9	arg1	Microcapsules					17:29	Multilayer Bixin Microcapsules	0:29	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.	0:128	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	11	34	theme	microcrystalline	1413:1428	arg1	form					1430:1433	its native microcrystalline form	1402:1433	its native microcrystalline form	1402:1433	The native carbohydrates allowed the encapsulation of bixin in its native microcrystalline form, resulting in a multilayer structure after spray-drying.
30909470	6	35	theme	sedimentation	824:836	arg1	analyses					838:845	turbidometric sedimentation analyses	810:845	turbidometric sedimentation analyses	810:845	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	9	36	theme	native	1178:1183	arg1	fraction					1198:1205	this native carbohydrate fraction	1173:1205	this native carbohydrate fraction	1173:1205	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	8	37	theme	encapsulation	1086:1098	arg1	efficiency					1100:1109	the encapsulation efficiency	1082:1109	the encapsulation efficiency of other encapsulating materials	1082:1142	The results show that the native carbohydrates enhance the encapsulation efficiency of other encapsulating materials.
30909470	3	38	theme	alkaline	402:409	arg1	dispersion					417:426	a mild alkaline bixin dispersion	395:426	a mild alkaline bixin dispersion with different encapsulating materials	395:465	Microencapsulated systems were obtained by spray-drying a mild alkaline bixin dispersion with different encapsulating materials.
30909470	12	39	theme	colorant	1509:1516	arg1	particles					1518:1526	the colorant particles	1505:1526	the colorant particles	1505:1526	In addition, the colorant particles displayed dispersibility under acidic aqueous conditions suggesting that they are stabilized by the native carbohydrates after the microcapsules are dissolved.
30909470	6	40	theme	turbidometric	810:822	arg1	analyses					838:845	turbidometric sedimentation analyses	810:845	turbidometric sedimentation analyses	810:845	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	3	41	with	dispersion	417:426	arg1	materials					457:465	different encapsulating materials	433:465	different encapsulating materials	433:465	Microencapsulated systems were obtained by spray-drying a mild alkaline bixin dispersion with different encapsulating materials.
30909470	9	42	theme	carbohydrate	1185:1196	arg1	fraction					1198:1205	this native carbohydrate fraction	1173:1205	this native carbohydrate fraction	1173:1205	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	1	43	theme	seeds	197:201	arg1	integument					179:188	the integument	175:188	the integument of the seeds of Bixa orellana	175:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	3	44	theme	bixin	411:415	arg1	dispersion					417:426	a mild alkaline bixin dispersion	395:426	a mild alkaline bixin dispersion with different encapsulating materials	395:465	Microencapsulated systems were obtained by spray-drying a mild alkaline bixin dispersion with different encapsulating materials.
30909470	11	45	theme	native	1343:1348	arg1	carbohydrates					1350:1362	The native carbohydrates	1339:1362	The native carbohydrates	1339:1362	The native carbohydrates allowed the encapsulation of bixin in its native microcrystalline form, resulting in a multilayer structure after spray-drying.
30909470	7	46	theme	UV-vis	980:985	arg1	spectra					987:993	UV-vis spectra	980:993	UV-vis spectra	980:993	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	9	47	theme	fraction	1198:1205	arg1	composition					1158:1168	The chemical composition	1145:1168	The chemical composition of this native carbohydrate fraction	1145:1205	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	7	48	from	pH	1021:1022	arg1	stability					1008:1016	physical stability	999:1016	physical stability	999:1016	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	7	48	from	pH	1021:1022	arg1	differences					945:955	differences	945:955	differences in their transparency, UV-vis spectra and physical stability at pH 3	945:1024	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	7	48	from	pH	1021:1022	arg1	transparency					966:977	their transparency	960:977	their transparency	960:977	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	7	48	from	pH	1021:1022	arg1	spectra					987:993	UV-vis spectra	980:993	UV-vis spectra	980:993	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	5	49	theme	total	668:672	arg1	solids					674:679	total solids	668:679	total solids	668:679	It was possible to dry dispersions with up to 10% bixin counted on total solids.
30909470	1	50	theme	Bixa	206:209	arg1	orellana					211:218	Bixa orellana	206:218	Bixa orellana	206:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	6	51	theme	studied	690:696	arg1	systems					698:704	All the studied systems	682:704	All the studied systems	682:704	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	4	52	theme	main	583:586	arg1	encapsulant					588:598	the main encapsulant	579:598	the main encapsulant	579:598	The encapsulation trials were performed with and without native carbohydrates of the integument in addition to the main encapsulant.
30909470	12	53	theme	aqueous	1566:1572	arg1	conditions					1574:1583	acidic aqueous conditions	1559:1583	acidic aqueous conditions	1559:1583	In addition, the colorant particles displayed dispersibility under acidic aqueous conditions suggesting that they are stabilized by the native carbohydrates after the microcapsules are dissolved.
30909470	1	54	theme	orellana	211:218	arg1	seeds					197:201	the seeds	193:201	the seeds of Bixa orellana	193:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	3	55	theme	different	433:441	arg1	materials					457:465	different encapsulating materials	433:465	different encapsulating materials	433:465	Microencapsulated systems were obtained by spray-drying a mild alkaline bixin dispersion with different encapsulating materials.
30909470	0	56	theme	Carbohydrates	53:65	arg1	Impact					36:41	The Impact	32:41	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.	0:128	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	3	57	theme	encapsulating	443:455	arg1	materials					457:465	different encapsulating materials	433:465	different encapsulating materials	433:465	Microencapsulated systems were obtained by spray-drying a mild alkaline bixin dispersion with different encapsulating materials.
30909470	4	58	theme	encapsulation	472:484	arg1	trials					486:491	The encapsulation trials	468:491	The encapsulation trials	468:491	The encapsulation trials were performed with and without native carbohydrates of the integument in addition to the main encapsulant.
30909470	9	59	contain	containing	1245:1254	arg2	galactose					1267:1275	galactose	1267:1275	galactose	1267:1275	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	9	59	contain	containing	1245:1254	arg2	arabinose					1256:1264	arabinose	1256:1264	arabinose	1256:1264	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	9	59	contain	containing	1245:1254	arg1	polysaccharides					1229:1243	polysaccharides	1229:1243	polysaccharides containing arabinose, galactose and glucose as monomers	1229:1299	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	9	59	contain	containing	1245:1254	arg2	monomers					1292:1299	monomers	1292:1299	monomers	1292:1299	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	9	59	contain	containing	1245:1254	arg2	glucose					1281:1287	glucose	1281:1287	glucose	1281:1287	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	6	60	theme	light	792:796	arg1	microscopy					798:807	light microscopy	792:807	light microscopy	792:807	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	5	61	dep	%	649:649	arg1	10					647:648	10	647:648	10	647:648	It was possible to dry dispersions with up to 10% bixin counted on total solids.
30909470	7	62	theme	physical	999:1006	arg1	stability					1008:1016	physical stability	999:1016	physical stability	999:1016	All the systems showed aqueous dispersibility but displayed differences in their transparency, UV-vis spectra and physical stability at pH 3.
30909470	2	63	theme	dispersible	268:278	arg1	formulations					280:291	water dispersible formulations	262:291	water dispersible formulations	262:291	Microencapsulation was applied to obtain water dispersible formulations and protect the colorant against degradation.
30909470	9	64	theme	polysaccharides	1229:1243	arg1	presence					1217:1224	the presence	1213:1224	the presence of polysaccharides containing arabinose, galactose and glucose as monomers	1213:1299	The chemical composition of this native carbohydrate fraction shows the presence of polysaccharides containing arabinose, galactose and glucose as monomers.
30909470	5	65	dep	bixin	651:655	arg1	%					649:649	%	649:649	%	649:649	It was possible to dry dispersions with up to 10% bixin counted on total solids.
30909470	12	66	theme	native	1628:1633	arg1	carbohydrates					1635:1647	the native carbohydrates	1624:1647	the native carbohydrates	1624:1647	In addition, the colorant particles displayed dispersibility under acidic aqueous conditions suggesting that they are stabilized by the native carbohydrates after the microcapsules are dissolved.
30909470	0	67	dep	Microcapsules	17:29	arg1	Impact					36:41	The Impact	32:41	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.	0:128	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	6	68	theme	Electron	771:778	arg1	Microscopy					780:789	Scanning Electron Microscopy	762:789	Scanning Electron Microscopy	762:789	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	1	69	theme	hydrophobic	141:151	arg1	carotenoid					153:162	a hydrophobic carotenoid	139:162	a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana	139:218	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	1	69	theme	hydrophobic	141:151	arg1	Bixin					130:134	Bixin	130:134	Bixin	130:134	Bixin is a hydrophobic carotenoid present in the integument of the seeds of Bixa orellana.
30909470	5	70	dep	10	647:648	arg1	to					644:645	to	644:645	to	644:645	It was possible to dry dispersions with up to 10% bixin counted on total solids.
30909470	0	71	theme	Native	46:51	arg1	Carbohydrates					53:65	Native Carbohydrates	46:65	Native Carbohydrates	46:65	Multilayer Bixin Microcapsules: The Impact of Native Carbohydrates on the Microencapsulation Efficiency and Dispersion Stability.
30909470	6	72	theme	Scanning	762:769	arg1	Microscopy					780:789	Scanning Electron Microscopy	762:789	Scanning Electron Microscopy	762:789	All the studied systems were characterized by colorimetry, UV-vis spectroscopy, Scanning Electron Microscopy, light microscopy, turbidometric sedimentation analyses and laser light diffraction analyses.
30909470	11	73	from	encapsulation	1376:1388	arg1	form					1430:1433	its native microcrystalline form	1402:1433	its native microcrystalline form	1402:1433	The native carbohydrates allowed the encapsulation of bixin in its native microcrystalline form, resulting in a multilayer structure after spray-drying.
31547343	10	0	theme	sp	1296:1297	arg1	fractions					1278:1286	poly- and oligosaccharidic fractions	1251:1286	poly- and oligosaccharidic fractions of Ulva sp	1251:1297	Our research emphasizes the potential use of poly- and oligosaccharidic fractions of Ulva sp.
31547343	5	1	theme	ammonium	648:655	arg1	precipitation					657:669	sulfate ammonium precipitation	640:669	sulfate ammonium precipitation	640:669	Coupling EAE to sulfate ammonium precipitation led to protein enrichment.
31547343	6	2	theme	radical	738:744	arg1	depolymerization					746:761	radical depolymerization	738:761	radical depolymerization by H2O2 and ion-exchange resin depolymerization	738:809	Oligosaccharides were obtained by using radical depolymerization by H2O2 and ion-exchange resin depolymerization.
31547343	8	3	theme	potential	888:896	arg1	bioactivity					898:908	The potential bioactivity	884:908	The potential bioactivity of the fractions	884:925	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	4	4	from	content	605:611	arg1	ulvans					616:621	ulvans	616:621	ulvans	616:621	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	8	5	theme	dermal	1037:1042	arg1	viability					1055:1063	human dermal fibroblast viability	1031:1063	human dermal fibroblast viability	1031:1063	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	10	6	theme	fractions	1278:1286	arg1	use					1244:1246	the potential use	1230:1246	the potential use of poly- and oligosaccharidic fractions of Ulva sp	1230:1297	Our research emphasizes the potential use of poly- and oligosaccharidic fractions of Ulva sp.
31547343	8	7	theme	human	1031:1035	arg1	viability					1055:1063	human dermal fibroblast viability	1031:1063	human dermal fibroblast viability	1031:1063	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	4	8	theme	increased	595:603	arg1	content					605:611	an increased content	592:611	an increased content in ulvans	592:621	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	9	9	dep	rate	1190:1193	arg1	%					1203:1203	%	1203:1203	%	1203:1203	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	4	10	theme	fractionation	447:459	arg1	precipitation					482:494	different fractionation procedures-ethanolic precipitation	437:494	different fractionation procedures-ethanolic precipitation	437:494	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	2	11	from	studies	224:230	arg1	activities					250:259	the biological activities	235:259	the biological activities on skin cells	235:273	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	2	11	from	studies	224:230	arg1	depolymerization					166:181	depolymerization	166:181	depolymerization	166:181	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	2	11	from	studies	224:230	arg1	fractionation					148:160	fractionation	148:160	fractionation	148:160	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	10	12	theme	Ulva	1291:1294	arg1	sp					1296:1297	Ulva sp	1291:1297	Ulva sp	1291:1297	Our research emphasizes the potential use of poly- and oligosaccharidic fractions of Ulva sp.
31547343	4	13	theme	different	437:445	arg1	precipitation					482:494	different fractionation procedures-ethanolic precipitation	437:494	different fractionation procedures-ethanolic precipitation	437:494	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	5	14	theme	Coupling	624:631	arg1	EAE					633:635	Coupling EAE	624:635	Coupling EAE to sulfate ammonium precipitation	624:669	Coupling EAE to sulfate ammonium precipitation led to protein enrichment.
31547343	8	15	theme	fibroblast	1044:1053	arg1	viability					1055:1063	human dermal fibroblast viability	1031:1063	human dermal fibroblast viability	1031:1063	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	8	16	theme	fractions	917:925	arg1	bioactivity					898:908	The potential bioactivity	884:908	The potential bioactivity of the fractions	884:925	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	2	17	from	Data	140:143	arg1	activities					250:259	the biological activities	235:259	the biological activities on skin cells	235:273	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	2	17	from	Data	140:143	arg1	depolymerization					166:181	depolymerization	166:181	depolymerization	166:181	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	2	17	from	Data	140:143	arg1	fractionation					148:160	fractionation	148:160	fractionation	148:160	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	10	18	theme	oligosaccharidic	1261:1276	arg1	fractions					1278:1286	poly- and oligosaccharidic fractions	1251:1286	poly- and oligosaccharidic fractions of Ulva sp	1251:1297	Our research emphasizes the potential use of poly- and oligosaccharidic fractions of Ulva sp.
31547343	3	19	theme	established	407:417	arg1	maceration					392:401	maceration	392:401	maceration (an established procedure)	392:428	In this work, crude ulvans were produced by using EAE (enzyme-assisted extraction) and compared to maceration (an established procedure).
31547343	3	19	theme	established	407:417	arg1	procedure					419:427	an established procedure	404:427	an established procedure	404:427	In this work, crude ulvans were produced by using EAE (enzyme-assisted extraction) and compared to maceration (an established procedure).
31547343	3	20	theme	enzyme-assisted	348:362	arg1	EAE					343:345	EAE	343:345	EAE (enzyme-assisted extraction)	343:374	In this work, crude ulvans were produced by using EAE (enzyme-assisted extraction) and compared to maceration (an established procedure).
31547343	3	20	theme	enzyme-assisted	348:362	arg1	extraction					364:373	enzyme-assisted extraction	348:373	enzyme-assisted extraction	348:373	In this work, crude ulvans were produced by using EAE (enzyme-assisted extraction) and compared to maceration (an established procedure).
31547343	4	21	theme	procedures-ethanolic	461:480	arg1	precipitation					482:494	different fractionation procedures-ethanolic precipitation	437:494	different fractionation procedures-ethanolic precipitation	437:494	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	9	22	dep	62	1201:1202	arg1	to					1198:1199	to	1198:1199	to	1198:1199	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	9	23	theme	oligosaccharidic	1115:1130	arg1	fractions					1132:1140	poly- and oligosaccharidic fractions	1105:1140	poly- and oligosaccharidic fractions from EAE	1105:1149	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	9	23	theme	oligosaccharidic	1115:1130	arg1	extracts					1095:1102	All ulvans extracts	1084:1102	All ulvans extracts	1084:1102	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	5	24	theme	sulfate	640:646	arg1	precipitation					657:669	sulfate ammonium precipitation	640:669	sulfate ammonium precipitation	640:669	Coupling EAE to sulfate ammonium precipitation led to protein enrichment.
31547343	1	25	theme	Enzyme-Assisted	85:99	arg1	EAE					113:115	EAE	113:115	EAE	113:115	by Combining Enzyme-Assisted Extraction (EAE) and Depolymerization.
31547343	1	25	theme	Enzyme-Assisted	85:99	arg1	Extraction					101:110	Enzyme-Assisted Extraction	85:110	Enzyme-Assisted Extraction (EAE)	85:116	by Combining Enzyme-Assisted Extraction (EAE) and Depolymerization.
31547343	2	26	from	activities	250:259	arg1	cells					269:273	skin cells	264:273	skin cells	264:273	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	0	27	theme	Poly-	21:25	arg1	Fractions					48:56	Active Poly- and Oligosaccharidic Fractions	14:56	Active Poly- and Oligosaccharidic Fractions	14:56	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.
31547343	9	28	dep	%	1203:1203	arg1	62					1201:1202	62	1201:1202	62	1201:1202	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	9	29	theme	proliferation	1176:1188	arg1	rate					1190:1193	the fibroblast proliferation rate	1161:1193	the fibroblast proliferation rate up to 62%	1161:1203	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	0	30	theme	Active	14:19	arg1	Fractions					48:56	Active Poly- and Oligosaccharidic Fractions	14:56	Active Poly- and Oligosaccharidic Fractions	14:56	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.
31547343	7	31	theme	chemical	863:870	arg1	treatments					872:881	these chemical treatments	857:881	these chemical treatments	857:881	Sulfate groups were partially cleaved during these chemical treatments.
31547343	8	32	theme	lipoxygenase	948:959	arg1	assay					972:976	a lipoxygenase inhibition assay	946:976	a lipoxygenase inhibition assay for anti-inflammatory activity	946:1007	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	0	33	theme	Oligosaccharidic	31:46	arg1	Fractions					48:56	Active Poly- and Oligosaccharidic Fractions	14:56	Active Poly- and Oligosaccharidic Fractions	14:56	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.
31547343	8	34	theme	inhibition	961:970	arg1	assay					972:976	a lipoxygenase inhibition assay	946:976	a lipoxygenase inhibition assay for anti-inflammatory activity	946:1007	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	0	35	from	sp	68:69	arg1	Production					0:9	Production	0:9	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.	0:70	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.
31547343	8	36	theme	anti-inflammatory	982:998	arg1	activity					1000:1007	anti-inflammatory activity	982:1007	anti-inflammatory activity	982:1007	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	7	37	theme	Sulfate	812:818	arg1	groups					820:825	Sulfate groups	812:825	Sulfate groups	812:825	Sulfate groups were partially cleaved during these chemical treatments.
31547343	4	38	theme	ammonium	510:517	arg1	sulfate					519:525	ammonium sulfate	510:525	ammonium sulfate	510:525	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	5	39	theme	protein	678:684	arg1	enrichment					686:695	protein enrichment	678:695	protein enrichment	678:695	Coupling EAE to sulfate ammonium precipitation led to protein enrichment.
31547343	0	40	theme	Fractions	48:56	arg1	Production					0:9	Production	0:9	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.	0:70	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.
31547343	4	41	theme	biochemical	545:555	arg1	composition					557:567	precipitation-the biochemical composition	527:567	precipitation-the biochemical composition	527:567	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	11	42	theme	cosmetic	1327:1334	arg1	applications					1336:1347	cosmetic applications	1327:1347	cosmetic applications	1327:1347	for further development in cosmetic applications.
31547343	6	43	theme	ion-exchange	775:786	arg1	resin					788:792	ion-exchange resin	775:792	ion-exchange resin	775:792	Oligosaccharides were obtained by using radical depolymerization by H2O2 and ion-exchange resin depolymerization.
31547343	9	44	theme	ulvans	1088:1093	arg1	fractions					1132:1140	poly- and oligosaccharidic fractions	1105:1140	poly- and oligosaccharidic fractions from EAE	1105:1149	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	9	44	theme	ulvans	1088:1093	arg1	extracts					1095:1102	All ulvans extracts	1084:1102	All ulvans extracts	1084:1102	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	4	45	theme	precipitation-the	527:543	arg1	composition					557:567	precipitation-the biochemical composition	527:567	precipitation-the biochemical composition	527:567	After different fractionation procedures-ethanolic precipitation, dialysis, or ammonium sulfate precipitation-the biochemical composition showed that EAE led to an increased content in ulvans.
31547343	11	46	theme	further	1304:1310	arg1	development					1312:1322	further development	1304:1322	further development in cosmetic applications	1304:1347	for further development in cosmetic applications.
31547343	2	47	theme	polysaccharides	203:217	arg1	depolymerization					166:181	depolymerization	166:181	depolymerization	166:181	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	2	47	theme	polysaccharides	203:217	arg1	fractionation					148:160	fractionation	148:160	fractionation	148:160	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	2	48	theme	skin	264:267	arg1	cells					269:273	skin cells	264:273	skin cells	264:273	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	9	49	theme	fibroblast	1165:1174	arg1	rate					1190:1193	the fibroblast proliferation rate	1161:1193	the fibroblast proliferation rate up to 62%	1161:1203	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	10	50	theme	poly-	1251:1255	arg1	fractions					1278:1286	poly- and oligosaccharidic fractions	1251:1286	poly- and oligosaccharidic fractions of Ulva sp	1251:1297	Our research emphasizes the potential use of poly- and oligosaccharidic fractions of Ulva sp.
31547343	2	51	theme	ulvan	197:201	arg1	polysaccharides					203:217	the matrix ulvan polysaccharides	186:217	the matrix ulvan polysaccharides	186:217	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	8	52	theme	WST-1	1015:1019	arg1	assay					1021:1025	a WST-1 assay	1013:1025	a WST-1 assay for human dermal fibroblast viability and proliferation	1013:1081	The potential bioactivity of the fractions was assessed using a lipoxygenase inhibition assay for anti-inflammatory activity and a WST-1 assay for human dermal fibroblast viability and proliferation.
31547343	6	53	dep	H2O2	766:769	arg1	depolymerization					794:809	depolymerization	794:809	depolymerization	794:809	Oligosaccharides were obtained by using radical depolymerization by H2O2 and ion-exchange resin depolymerization.
31547343	11	54	from	development	1312:1322	arg1	applications					1336:1347	cosmetic applications	1327:1347	cosmetic applications	1327:1347	for further development in cosmetic applications.
31547343	3	55	theme	crude	307:311	arg1	ulvans					313:318	crude ulvans	307:318	crude ulvans	307:318	In this work, crude ulvans were produced by using EAE (enzyme-assisted extraction) and compared to maceration (an established procedure).
31547343	2	56	theme	matrix	190:195	arg1	polysaccharides					203:217	the matrix ulvan polysaccharides	186:217	the matrix ulvan polysaccharides	186:217	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	9	57	from	EAE	1147:1149	arg1	fractions					1132:1140	poly- and oligosaccharidic fractions	1105:1140	poly- and oligosaccharidic fractions from EAE	1105:1149	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	9	57	from	EAE	1147:1149	arg1	extracts					1095:1102	All ulvans extracts	1084:1102	All ulvans extracts	1084:1102	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	9	58	theme	poly-	1105:1109	arg1	fractions					1132:1140	poly- and oligosaccharidic fractions	1105:1140	poly- and oligosaccharidic fractions from EAE	1105:1149	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	9	58	theme	poly-	1105:1109	arg1	extracts					1095:1102	All ulvans extracts	1084:1102	All ulvans extracts	1084:1102	All ulvans extracts, poly- and oligosaccharidic fractions from EAE, expanded the fibroblast proliferation rate up to 62%.
31547343	0	59	theme	Ulva	63:66	arg1	sp					68:69	Ulva sp	63:69	Ulva sp	63:69	Production of Active Poly- and Oligosaccharidic Fractions from Ulva sp.
31547343	2	60	theme	biological	239:248	arg1	activities					250:259	the biological activities	235:259	the biological activities on skin cells	235:273	Data on fractionation and depolymerization of the matrix ulvan polysaccharides, and studies on the biological activities on skin cells, are very scarce.
31547343	10	61	theme	potential	1234:1242	arg1	use					1244:1246	the potential use	1230:1246	the potential use of poly- and oligosaccharidic fractions of Ulva sp	1230:1297	Our research emphasizes the potential use of poly- and oligosaccharidic fractions of Ulva sp.
30525943	12	0	theme	P	1223:1223	arg1	hens					1217:1220	Flax+E2 hens	1209:1220	Flax+E2 hens (P < 0.05)	1209:1231	ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05).
30525943	12	0	theme	P	1223:1223	arg1	< 0.05					1225:1230	P < 0.05	1223:1230	P < 0.05	1223:1230	ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05).
30525943	3	1	theme	Feeding	196:202	arg1	flaxseed					204:211	Feeding flaxseed	196:211	Feeding flaxseed to hens	196:219	Feeding flaxseed to hens can increase n-3 fatty acids (FA) in eggs.
30525943	13	2	from	hens	1363:1366	arg1	eggs					1353:1356	eggs	1353:1356	eggs from hens fed flaxseed-based diets (P > 0.05)	1353:1402	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	2	3	dep	acid	174:177	arg1	ALA					180:182	ALA	180:182	ALA	180:182	Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3).
30525943	2	3	dep	acid	174:177	arg1	18:3 n-3					185:192	18:3 n-3	185:192	18:3 n-3	185:192	Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3).
30525943	2	4	theme	rich	147:150	arg1	source					152:157	a rich source	145:157	a rich source of α-linolenic acid (ALA, 18:3 n-3)	145:193	Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3).
30525943	2	4	theme	rich	147:150	arg1	Flaxseed					133:140	Flaxseed	133:140	Flaxseed	133:140	Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3).
30525943	18	5	dep	duodenum	1833:1840	arg1	the					1829:1831	the	1829:1831	the	1829:1831	Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05).
30525943	5	6	theme	enzymes	435:441	arg1	Addition					410:417	Addition	410:417	Addition of carbohydrase enzymes to flaxseed-based diets	410:465	Addition of carbohydrase enzymes to flaxseed-based diets can decrease the anti-nutritive effects of NSP.
30525943	14	7	theme	Over	1405:1408	arg1	increase					1420:1427	Over nine-fold increase	1405:1427	Over nine-fold increase in hepatic ALA	1405:1442	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	8	8	theme	%	888:888	arg1	Flax					896:899	Flax	896:899	Flax	896:899	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	8	theme	%	888:888	arg1	flax					890:893	10% flax	886:893	10% flax (Flax)	886:900	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	22	9	theme	gastrointestinal	2255:2270	arg1	morphology					2272:2281	gastrointestinal morphology in layer hens fed flaxseed	2255:2308	gastrointestinal morphology in layer hens fed flaxseed	2255:2308	It was concluded that enzyme supplementation enhanced total n-3 FA deposition in eggs and liver and influence gastrointestinal morphology in layer hens fed flaxseed.
30525943	5	10	theme	flaxseed-based	446:459	arg1	diets					461:465	flaxseed-based diets	446:465	flaxseed-based diets	446:465	Addition of carbohydrase enzymes to flaxseed-based diets can decrease the anti-nutritive effects of NSP.
30525943	12	11	theme	total	1171:1175	arg1	FA					1181:1182	total n-3 FA	1171:1182	total n-3 FA	1171:1182	ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05).
30525943	15	12	theme	supplementation	1573:1587	arg1	effect					1556:1561	No effect	1553:1561	No effect of enzyme supplementation	1553:1587	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	0	13	with	flaxseed	92:99	arg1	supplementation					113:127	enzyme supplementation	106:127	enzyme supplementation	106:127	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	19	14	from	jejunum	1979:1985	arg1	hens					2001:2004	hens	2001:2004	hens fed Flax+E2 (P < 0.05)	2001:2027	Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05).
30525943	20	15	theme	crypt	2097:2101	arg1	depth					2103:2107	crypt depth	2097:2107	height:crypt depth ratio	2090:2113	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	4	16	theme	egg	384:386	arg1	incorporation					395:407	egg n-3 FA incorporation	384:407	egg n-3 FA incorporation	384:407	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	8	17	theme	51-week	694:700	arg1	hens					718:721	seventy-two, 51-week old brown layer hens	681:721	hens	718:721	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	Flax+E1					922:928	Flax+E1	922:928	Flax+E1	922:928	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	enzyme					945:950	Flax+0.1% enzyme	935:950	Flax+0.1% enzyme (Flax+E2)	935:960	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	Flax+E2					953:959	Flax+E2	953:959	Flax+E2	953:959	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg1	diet					851:854	diet	851:854	diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2)	851:960	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	flax					890:893	10% flax	886:893	10% flax (Flax)	886:900	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	flax					870:873	0% flax	867:873	0% flax (Control)	867:883	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	Flax					896:899	Flax	896:899	Flax	896:899	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	Control					876:882	Control	876:882	Control	876:882	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	18	contain	containing	856:865	arg2	enzyme					914:919	Flax+0.05% enzyme	903:919	Flax+0.05% enzyme (Flax+E1)	903:929	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	4	19	theme	FA	392:393	arg1	incorporation					395:407	egg n-3 FA incorporation	384:407	egg n-3 FA incorporation	384:407	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	18	20	theme	P	1908:1908	arg1	< 0.05					1910:1915	P < 0.05	1908:1915	P < 0.05	1908:1915	Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05).
30525943	18	20	theme	P	1908:1908	arg1	control					1899:1905	the control	1895:1905	the control (P < 0.05)	1895:1916	Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05).
30525943	16	21	theme	P	1778:1778	arg1	diets					1771:1775	flaxseed-based diets	1756:1775	flaxseed-based diets (P > 0.05)	1756:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	21	theme	P	1778:1778	arg1	> 0.05					1780:1785	P > 0.05	1778:1785	P > 0.05	1778:1785	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	8	22	theme	brown	706:710	arg1	hens					718:721	seventy-two, 51-week old brown layer hens	681:721	hens	718:721	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	13	23	theme	long	1307:1310	arg1	chain					1312:1316	total long chain	1301:1316	total long chain (>20-C FA)	1301:1327	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	23	theme	long	1307:1310	arg1	FA					1325:1326	>20-C FA	1319:1326	>20-C FA	1319:1326	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	5	24	theme	NSP	510:512	arg1	effects					499:505	the anti-nutritive effects	480:505	the anti-nutritive effects of NSP	480:512	Addition of carbohydrase enzymes to flaxseed-based diets can decrease the anti-nutritive effects of NSP.
30525943	18	25	theme	Villi	1792:1796	arg1	height					1798:1803	Villi height	1792:1803	Villi height	1792:1803	Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05).
30525943	8	26	theme	hens	718:721	arg1	total					672:676	A total	670:676	A total of seventy-two, 51-week old brown layer hens	670:721	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	14	27	theme	control	1526:1532	arg1	diet					1534:1537	the control diet	1522:1537	the control diet (P < 0.0001)	1522:1550	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	14	27	theme	control	1526:1532	arg1	P					1540:1540	P < 0.0001	1540:1549	P < 0.0001	1540:1549	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	8	28	theme	treatments	773:782	arg1	treatments					773:782	the four dietary treatments	756:782	the four dietary treatments	756:782	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	28	theme	treatments	773:782	arg1	one					749:751	one	749:751	one	749:751	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	19	29	from	increase	1952:1959	arg1	P					1988:1988	P < 0.05	1988:1995	P < 0.05	1988:1995	Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05).
30525943	19	29	from	increase	1952:1959	arg1	villi					1964:1968	villi width	1964:1974	villi width	1964:1974	Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05).
30525943	19	29	from	increase	1952:1959	arg1	jejunum					1979:1985	jejunum	1979:1985	jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05)	1979:2027	Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05).
30525943	14	30	theme	nine-fold	1410:1418	arg1	increase					1420:1427	Over nine-fold increase	1405:1427	Over nine-fold increase in hepatic ALA	1405:1442	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	7	31	theme	FA	601:602	arg1	composition					604:614	FA composition	601:614	FA composition	601:614	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	22	32	theme	total	2199:2203	arg1	deposition					2212:2221	total n-3 FA deposition	2199:2221	total n-3 FA deposition	2199:2221	It was concluded that enzyme supplementation enhanced total n-3 FA deposition in eggs and liver and influence gastrointestinal morphology in layer hens fed flaxseed.
30525943	7	33	from	morphology	637:646	arg1	hens					651:654	hens	651:654	hens fed flaxseed	651:667	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	13	34	from	effect	1260:1265	arg1	chain					1312:1316	total long chain	1301:1316	total long chain (>20-C FA)	1301:1327	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	34	from	effect	1260:1265	arg1	ratio					1344:1348	n-6:n-3 FA ratio	1333:1348	n-6:n-3 FA ratio	1333:1348	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	34	from	effect	1260:1265	arg1	DHA					1295:1297	DHA	1295:1297	DHA	1295:1297	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	34	from	effect	1260:1265	arg1	acid					1289:1292	docosahexaenoic acid	1273:1292	docosahexaenoic acid (DHA)	1273:1298	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	34	from	effect	1260:1265	arg1	FA					1325:1326	>20-C FA	1319:1326	>20-C FA	1319:1326	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	0	35	theme	hens	77:80	arg1	quality					4:10	Egg quality	0:10	Egg quality	0:10	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	0	35	theme	hens	77:80	arg1	composition					24:34	fatty-acid composition	13:34	fatty-acid composition	13:34	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	0	35	theme	hens	77:80	arg1	morphology					57:66	gastrointestinal morphology	40:66	gastrointestinal morphology	40:66	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	7	36	theme	supplementation	582:596	arg1	effect					565:570	the effect	561:570	the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed	561:667	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	8	37	theme	Flax+0.05	903:911	arg1	enzyme					914:919	Flax+0.05% enzyme	903:919	Flax+0.05% enzyme (Flax+E1)	903:929	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	37	theme	Flax+0.05	903:911	arg1	Flax+E1					922:928	Flax+E1	922:928	Flax+E1	922:928	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	16	38	theme	n-6	1719:1721	arg1	FA					1723:1724	LC n-6 FA	1716:1724	LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05)	1716:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	0	39	theme	whole	86:90	arg1	flaxseed					92:99	whole flaxseed	86:99	whole flaxseed with enzyme supplementation	86:127	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	14	40	from	increase	1420:1427	arg1	ALA					1440:1442	hepatic ALA	1432:1442	hepatic ALA	1432:1442	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	18	41	theme	flax-based	1866:1875	arg1	diets					1877:1881	flax-based diets	1866:1881	flax-based diets compared to the control (P < 0.05)	1866:1916	Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05).
30525943	16	42	from	n-6	1708:1710	arg1	hens					1747:1750	hens	1747:1750	hens fed flaxseed-based diets (P > 0.05)	1747:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	42	from	n-6	1708:1710	arg1	tissue					1735:1740	liver tissue	1729:1740	liver tissue from hens fed flaxseed-based diets (P > 0.05)	1729:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	20	43	dep	depth	2074:2078	arg1	ratio					2109:2113	height:crypt depth ratio	2090:2113	height:crypt depth ratio	2090:2113	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	0	44	theme	Egg	0:2	arg1	quality					4:10	Egg quality	0:10	Egg quality	0:10	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	18	45	theme	hens	1857:1860	arg1	jejunum					1846:1852	jejunum	1846:1852	jejunum	1846:1852	Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05).
30525943	18	45	theme	hens	1857:1860	arg1	duodenum					1833:1840	duodenum	1833:1840	duodenum	1833:1840	Villi height and width was higher in the duodenum and jejunum of hens fed flax-based diets compared to the control (P < 0.05).
30525943	16	46	theme	Enzyme	1653:1658	arg1	supplementation					1660:1674	Enzyme supplementation	1653:1674	Enzyme supplementation	1653:1674	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	8	47	theme	Flax+0.1	935:942	arg1	enzyme					945:950	Flax+0.1% enzyme	935:950	Flax+0.1% enzyme (Flax+E2)	935:960	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	47	theme	Flax+0.1	935:942	arg1	Flax+E2					953:959	Flax+E2	953:959	Flax+E2	953:959	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	11	48	dep	control	1100:1106	arg1	the					1096:1098	the	1096:1098	the	1096:1098	Yolk weight was higher in Flax+E1 compared with the control and Flax+E2 and was not different from Flax treatment.
30525943	2	49	theme	α-linolenic	162:172	arg1	acid					174:177	α-linolenic acid	162:177	α-linolenic acid (ALA, 18:3 n-3)	162:193	Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3).
30525943	13	50	theme	enzyme	1246:1251	arg1	Addition					1234:1241	Addition	1234:1241	Addition of enzyme	1234:1251	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	15	51	theme	n-3	1634:1636	arg1	FA					1638:1639	long chain n-3 FA	1623:1639	long chain n-3 FA (P > 0.05)	1623:1650	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	51	theme	n-3	1634:1636	arg1	> 0.05					1644:1649	P > 0.05	1642:1649	P > 0.05	1642:1649	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	0	52	theme	gastrointestinal	40:55	arg1	morphology					57:66	gastrointestinal morphology	40:66	gastrointestinal morphology	40:66	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	10	53	dep	highest	1008:1014	arg1	< 0.05					1039:1044	P < 0.05	1037:1044	P < 0.05	1037:1044	Egg weight was highest in hens fed Flax+E1 (P < 0.05).
30525943	8	54	theme	%	868:868	arg1	Control					876:882	Control	876:882	Control	876:882	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	54	theme	%	868:868	arg1	flax					870:873	0% flax	867:873	0% flax (Control)	867:883	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	13	55	theme	FA	1341:1342	arg1	ratio					1344:1348	n-6:n-3 FA ratio	1333:1348	n-6:n-3 FA ratio	1333:1348	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	20	56	located	observed	2052:2059	arg1	P					2131:2131	P > 0.05	2131:2138	P > 0.05	2131:2138	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	20	56	located	observed	2052:2059	arg1	jejunum					2122:2128	the jejunum	2118:2128	the jejunum (P > 0.05)	2118:2139	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	20	56	located	observed	2052:2059	arg2	effect					2033:2038	No effect	2030:2038	No effect of diet	2030:2046	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	20	56	located	observed	2052:2059	arg1	depth					2074:2078	the crypt depth	2064:2078	the crypt depth	2064:2078	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	20	56	located	observed	2052:2059	arg1	villi					2084:2088	villi	2084:2088	villi	2084:2088	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	22	57	theme	n-3	2205:2207	arg1	deposition					2212:2221	total n-3 FA deposition	2199:2221	total n-3 FA deposition	2199:2221	It was concluded that enzyme supplementation enhanced total n-3 FA deposition in eggs and liver and influence gastrointestinal morphology in layer hens fed flaxseed.
30525943	8	58	theme	120-day	967:973	arg1	trial					983:987	a 120-day feeding trial	965:987	a 120-day feeding trial	965:987	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	4	59	theme	non-starch	273:282	arg1	NSP					301:303	NSP	301:303	NSP	301:303	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	4	59	theme	non-starch	273:282	arg1	polysaccharides					284:298	non-starch polysaccharides	273:298	non-starch polysaccharides (NSP) in flaxseed	273:316	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	20	60	theme	diet	2043:2046	arg1	effect					2033:2038	No effect	2030:2038	No effect of diet	2030:2046	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	10	61	theme	P	1037:1037	arg1	< 0.05					1039:1044	P < 0.05	1037:1044	P < 0.05	1037:1044	Egg weight was highest in hens fed Flax+E1 (P < 0.05).
30525943	22	62	theme	layer	2286:2290	arg1	hens					2292:2295	layer hens	2286:2295	layer hens	2286:2295	It was concluded that enzyme supplementation enhanced total n-3 FA deposition in eggs and liver and influence gastrointestinal morphology in layer hens fed flaxseed.
30525943	19	63	theme	Enzyme	1919:1924	arg1	supplementation					1926:1940	Enzyme supplementation	1919:1940	Enzyme supplementation	1919:1940	Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05).
30525943	3	64	from	acids	244:248	arg1	eggs					258:261	eggs	258:261	eggs	258:261	Feeding flaxseed to hens can increase n-3 fatty acids (FA) in eggs.
30525943	12	65	from	hens	1217:1220	arg1	eggs					1199:1202	eggs	1199:1202	eggs from Flax+E2 hens (P < 0.05)	1199:1231	ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05).
30525943	12	66	theme	Flax+E2	1209:1215	arg1	hens					1217:1220	Flax+E2 hens	1209:1220	Flax+E2 hens (P < 0.05)	1209:1231	ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05).
30525943	12	66	theme	Flax+E2	1209:1215	arg1	< 0.05					1225:1230	P < 0.05	1223:1230	P < 0.05	1223:1230	ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05).
30525943	20	67	theme	depth	2103:2107	arg1	ratio					2109:2113	height:crypt depth ratio	2090:2113	height:crypt depth ratio	2090:2113	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	15	68	theme	enzyme	1566:1571	arg1	supplementation					1573:1587	enzyme supplementation	1566:1587	enzyme supplementation	1566:1587	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	16	69	from	hens	1747:1750	arg1	acid					1696:1699	arachidonic acid	1684:1699	arachidonic acid	1684:1699	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	69	from	hens	1747:1750	arg1	n-6					1708:1710	total n-6	1702:1710	total n-6	1702:1710	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	69	from	hens	1747:1750	arg1	FA					1723:1724	LC n-6 FA	1716:1724	LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05)	1716:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	69	from	hens	1747:1750	arg1	tissue					1735:1740	liver tissue	1729:1740	liver tissue from hens fed flaxseed-based diets (P > 0.05)	1729:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	4	70	theme	nutrient	327:334	arg1	digestibility					336:348	nutrient digestibility	327:348	nutrient digestibility	327:348	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	16	71	theme	flaxseed-based	1756:1769	arg1	diets					1771:1775	flaxseed-based diets	1756:1775	flaxseed-based diets (P > 0.05)	1756:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	71	theme	flaxseed-based	1756:1769	arg1	> 0.05					1780:1785	P > 0.05	1778:1785	P > 0.05	1778:1785	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	4	72	theme	n-3	388:390	arg1	incorporation					395:407	egg n-3 FA incorporation	384:407	egg n-3 FA incorporation	384:407	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	12	73	theme	n-3	1177:1179	arg1	FA					1181:1182	total n-3 FA	1171:1182	total n-3 FA	1171:1182	ALA and total n-3 FA was highest in eggs from Flax+E2 hens (P < 0.05).
30525943	5	74	theme	carbohydrase	422:433	arg1	enzymes					435:441	carbohydrase enzymes	422:441	carbohydrase enzymes	422:441	Addition of carbohydrase enzymes to flaxseed-based diets can decrease the anti-nutritive effects of NSP.
30525943	3	75	theme	fatty	238:242	arg1	acids					244:248	n-3 fatty acids	234:248	n-3 fatty acids (FA) in eggs	234:261	Feeding flaxseed to hens can increase n-3 fatty acids (FA) in eggs.
30525943	3	75	theme	fatty	238:242	arg1	FA					251:252	FA	251:252	FA	251:252	Feeding flaxseed to hens can increase n-3 fatty acids (FA) in eggs.
30525943	11	76	theme	Flax	1147:1150	arg1	treatment					1152:1160	Flax treatment	1147:1160	Flax treatment	1147:1160	Yolk weight was higher in Flax+E1 compared with the control and Flax+E2 and was not different from Flax treatment.
30525943	13	77	contain	has	1253:1255	arg1	Addition					1234:1241	Addition	1234:1241	Addition of enzyme	1234:1251	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	77	contain	has	1253:1255	arg2	effect					1260:1265	no effect	1257:1265	no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio	1257:1348	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	78	theme	total	1301:1305	arg1	chain					1312:1316	total long chain	1301:1316	total long chain (>20-C FA)	1301:1327	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	78	theme	total	1301:1305	arg1	FA					1325:1326	>20-C FA	1319:1326	>20-C FA	1319:1326	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	15	79	theme	long	1623:1626	arg1	FA					1638:1639	long chain n-3 FA	1623:1639	long chain n-3 FA (P > 0.05)	1623:1650	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	79	theme	long	1623:1626	arg1	> 0.05					1644:1649	P > 0.05	1642:1649	P > 0.05	1642:1649	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	4	80	theme	negative	365:372	arg1	impact					374:379	a negative impact	363:379	a negative impact	363:379	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	4	81	from	polysaccharides	284:298	arg1	flaxseed					309:316	flaxseed	309:316	flaxseed	309:316	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	8	82	theme	old	702:704	arg1	hens					718:721	seventy-two, 51-week old brown layer hens	681:721	hens	718:721	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	16	83	theme	total	1702:1706	arg1	n-6					1708:1710	total n-6	1702:1710	total n-6	1702:1710	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	13	84	theme	docosahexaenoic	1273:1287	arg1	DHA					1295:1297	DHA	1295:1297	DHA	1295:1297	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	84	theme	docosahexaenoic	1273:1287	arg1	acid					1289:1292	docosahexaenoic acid	1273:1292	docosahexaenoic acid (DHA)	1273:1298	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	8	85	theme	layer	712:716	arg1	hens					718:721	seventy-two, 51-week old brown layer hens	681:721	hens	718:721	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	0	86	theme	layer	71:75	arg1	hens					77:80	layer hens	71:80	layer hens	71:80	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	7	87	theme	gastrointestinal	620:635	arg1	morphology					637:646	gastrointestinal morphology	620:646	gastrointestinal morphology	620:646	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	8	88	theme	dietary	765:771	arg1	treatments					773:782	the four dietary treatments	756:782	the four dietary treatments	756:782	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	22	89	theme	enzyme	2167:2172	arg1	supplementation					2174:2188	enzyme supplementation	2167:2188	enzyme supplementation	2167:2188	It was concluded that enzyme supplementation enhanced total n-3 FA deposition in eggs and liver and influence gastrointestinal morphology in layer hens fed flaxseed.
30525943	11	90	from	treatment	1152:1160	arg1	different					1132:1140	different	1132:1140	different	1132:1140	Yolk weight was higher in Flax+E1 compared with the control and Flax+E2 and was not different from Flax treatment.
30525943	8	91	theme	%	912:912	arg1	enzyme					914:919	Flax+0.05% enzyme	903:919	Flax+0.05% enzyme (Flax+E1)	903:929	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	91	theme	%	912:912	arg1	Flax+E1					922:928	Flax+E1	922:928	Flax+E1	922:928	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	5	92	theme	anti-nutritive	484:497	arg1	effects					499:505	the anti-nutritive effects	480:505	the anti-nutritive effects of NSP	480:512	Addition of carbohydrase enzymes to flaxseed-based diets can decrease the anti-nutritive effects of NSP.
30525943	16	93	theme	LC	1716:1717	arg1	FA					1723:1724	LC n-6 FA	1716:1724	LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05)	1716:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	0	94	theme	enzyme	106:111	arg1	supplementation					113:127	enzyme supplementation	106:127	enzyme supplementation	106:127	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	7	95	theme	enzyme	575:580	arg1	supplementation					582:596	enzyme supplementation	575:596	enzyme supplementation	575:596	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	13	96	theme	flaxseed-based	1372:1385	arg1	diets					1387:1391	flaxseed-based diets	1372:1391	flaxseed-based diets (P > 0.05)	1372:1402	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	13	96	theme	flaxseed-based	1372:1385	arg1	P					1394:1394	P > 0.05	1394:1401	P > 0.05	1394:1401	Addition of enzyme has no effect of on docosahexaenoic acid (DHA), total long chain (>20-C FA), or n-6:n-3 FA ratio in eggs from hens fed flaxseed-based diets (P > 0.05).
30525943	7	97	from	effect	565:570	arg1	morphology					637:646	gastrointestinal morphology	620:646	gastrointestinal morphology	620:646	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	7	97	from	effect	565:570	arg1	composition					604:614	FA composition	601:614	FA composition	601:614	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	16	98	theme	liver	1729:1733	arg1	tissue					1735:1740	liver tissue	1729:1740	liver tissue from hens fed flaxseed-based diets (P > 0.05)	1729:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	0	99	theme	fatty-acid	13:22	arg1	composition					24:34	fatty-acid composition	13:34	fatty-acid composition	13:34	Egg quality, fatty-acid composition and gastrointestinal morphology of layer hens fed whole flaxseed with enzyme supplementation.
30525943	14	100	theme	flaxseed-based	1482:1495	arg1	diets					1497:1501	flaxseed-based diets	1482:1501	flaxseed-based diets	1482:1501	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	8	101	theme	%	943:943	arg1	enzyme					945:950	Flax+0.1% enzyme	935:950	Flax+0.1% enzyme (Flax+E2)	935:960	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	8	101	theme	%	943:943	arg1	Flax+E2					953:959	Flax+E2	953:959	Flax+E2	953:959	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	11	102	theme	Yolk	1048:1051	arg1	weight					1053:1058	Yolk weight	1048:1058	Yolk weight	1048:1058	Yolk weight was higher in Flax+E1 compared with the control and Flax+E2 and was not different from Flax treatment.
30525943	2	103	theme	acid	174:177	arg1	source					152:157	a rich source	145:157	a rich source of α-linolenic acid (ALA, 18:3 n-3)	145:193	Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3).
30525943	2	103	theme	acid	174:177	arg1	Flaxseed					133:140	Flaxseed	133:140	Flaxseed	133:140	Flaxseed is a rich source of α-linolenic acid (ALA, 18:3 n-3).
30525943	14	104	located	observed	1448:1455	arg1	liver					1464:1468	the liver	1460:1468	the liver of hens fed flaxseed-based diets	1460:1501	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	14	104	located	observed	1448:1455	arg2	increase					1420:1427	Over nine-fold increase	1405:1427	Over nine-fold increase in hepatic ALA	1405:1442	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	14	105	theme	hens	1473:1476	arg1	liver					1464:1468	the liver	1460:1468	the liver of hens fed flaxseed-based diets	1460:1501	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30525943	4	106	contain	have	358:361	arg1	NSP					301:303	NSP	301:303	NSP	301:303	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	4	106	contain	have	358:361	arg1	polysaccharides					284:298	non-starch polysaccharides	273:298	non-starch polysaccharides (NSP) in flaxseed	273:316	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	4	106	contain	have	358:361	arg2	impact					374:379	a negative impact	363:379	a negative impact	363:379	However, non-starch polysaccharides (NSP) in flaxseed decrease nutrient digestibility and can have a negative impact on egg n-3 FA incorporation.
30525943	15	107	theme	P	1642:1642	arg1	FA					1638:1639	long chain n-3 FA	1623:1639	long chain n-3 FA (P > 0.05)	1623:1650	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	107	theme	P	1642:1642	arg1	> 0.05					1644:1649	P > 0.05	1642:1649	P > 0.05	1642:1649	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	10	108	theme	Egg	993:995	arg1	weight					997:1002	Egg weight	993:1002	Egg weight	993:1002	Egg weight was highest in hens fed Flax+E1 (P < 0.05).
30525943	16	109	from	acid	1696:1699	arg1	hens					1747:1750	hens	1747:1750	hens fed flaxseed-based diets (P > 0.05)	1747:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	109	from	acid	1696:1699	arg1	tissue					1735:1740	liver tissue	1729:1740	liver tissue from hens fed flaxseed-based diets (P > 0.05)	1729:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	7	110	from	composition	604:614	arg1	hens					651:654	hens	651:654	hens fed flaxseed	651:667	An experiment was conducted to investigate the effect of enzyme supplementation on FA composition and gastrointestinal morphology in hens fed flaxseed.
30525943	16	111	theme	arachidonic	1684:1694	arg1	acid					1696:1699	arachidonic acid	1684:1699	arachidonic acid	1684:1699	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	15	112	theme	liver	1605:1609	arg1	ALA					1611:1613	liver ALA	1605:1613	liver ALA	1605:1613	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	20	113	theme	crypt	2068:2072	arg1	depth					2074:2078	the crypt depth	2064:2078	the crypt depth	2064:2078	No effect of diet was observed in the crypt depth and villi height:crypt depth ratio in the jejunum (P > 0.05).
30525943	16	114	from	FA	1723:1724	arg1	hens					1747:1750	hens	1747:1750	hens fed flaxseed-based diets (P > 0.05)	1747:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	16	114	from	FA	1723:1724	arg1	tissue					1735:1740	liver tissue	1729:1740	liver tissue from hens fed flaxseed-based diets (P > 0.05)	1729:1786	Enzyme supplementation reduced arachidonic acid, total n-6 and LC n-6 FA in liver tissue from hens fed flaxseed-based diets (P > 0.05).
30525943	8	115	theme	0	867:867	arg1	%					868:868	%	868:868	%	868:868	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	15	116	theme	chain	1628:1632	arg1	FA					1638:1639	long chain n-3 FA	1623:1639	long chain n-3 FA (P > 0.05)	1623:1650	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	116	theme	chain	1628:1632	arg1	> 0.05					1644:1649	P > 0.05	1642:1649	P > 0.05	1642:1649	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	22	117	theme	FA	2209:2210	arg1	deposition					2212:2221	total n-3 FA deposition	2199:2221	total n-3 FA deposition	2199:2221	It was concluded that enzyme supplementation enhanced total n-3 FA deposition in eggs and liver and influence gastrointestinal morphology in layer hens fed flaxseed.
30525943	15	118	located	observed	1593:1600	arg1	> 0.05					1644:1649	P > 0.05	1642:1649	P > 0.05	1642:1649	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	118	located	observed	1593:1600	arg1	FA					1638:1639	long chain n-3 FA	1623:1639	long chain n-3 FA (P > 0.05)	1623:1650	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	118	located	observed	1593:1600	arg1	DHA					1616:1618	DHA	1616:1618	DHA	1616:1618	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	118	located	observed	1593:1600	arg2	effect					1556:1561	No effect	1553:1561	No effect of enzyme supplementation	1553:1587	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	15	118	located	observed	1593:1600	arg1	ALA					1611:1613	liver ALA	1605:1613	liver ALA	1605:1613	No effect of enzyme supplementation was observed on liver ALA, DHA or long chain n-3 FA (P > 0.05).
30525943	8	119	theme	feeding	975:981	arg1	trial					983:987	a 120-day feeding trial	965:987	a 120-day feeding trial	965:987	A total of seventy-two, 51-week old brown layer hens were randomly assigned to one of the four dietary treatments (six replicates with three hens per replicate): corn-soybean based diet containing 0% flax (Control), 10% flax (Flax), Flax+0.05% enzyme (Flax+E1), or Flax+0.1% enzyme (Flax+E2) in a 120-day feeding trial.
30525943	19	120	theme	P	2019:2019	arg1	< 0.05					2021:2026	P < 0.05	2019:2026	P < 0.05	2019:2026	Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05).
30525943	19	120	theme	P	2019:2019	arg1	Flax+E2					2010:2016	Flax+E2	2010:2016	Flax+E2 (P < 0.05)	2010:2027	Enzyme supplementation led to an increase in villi width in jejunum (P < 0.05) in hens fed Flax+E2 (P < 0.05).
30525943	14	121	theme	hepatic	1432:1438	arg1	ALA					1440:1442	hepatic ALA	1432:1442	hepatic ALA	1432:1442	Over nine-fold increase in hepatic ALA was observed in the liver of hens fed flaxseed-based diets when compared with the control diet (P < 0.0001).
30852271	0	0	theme	ER	104:105	arg1	response					114:121	infectious bronchitis virus-induced ER stress response	68:121	infectious bronchitis virus-induced ER stress response	68:121	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	4	1	theme	virus-like	662:671	arg1	formation					682:690	virus-like particle formation	662:690	virus-like particle formation	662:690	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	1	2	theme	M	174:174	arg1	protein					177:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	1	2	theme	M	174:174	arg1	protein					217:223	the most abundant structural protein	188:223	the most abundant structural protein playing a critical role in virion assembly	188:266	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	1	3	theme	virion	252:257	arg1	assembly					259:266	virion assembly	252:266	virion assembly	252:266	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	0	4	theme	virus-induced	90:102	arg1	response					114:121	infectious bronchitis virus-induced ER stress response	68:121	infectious bronchitis virus-induced ER stress response	68:121	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	3	5	theme	predicted	498:506	arg1	sites					508:512	two predicted sites	494:512	two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV)	494:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	4	6	from	assembly	652:659	arg1	cells					725:729	culture cells	717:729	culture cells	717:729	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	6	7	theme	important	1071:1079	arg1	roles					1081:1085	important roles	1071:1085	important roles	1071:1085	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	3	8	theme	protein	523:529	arg1	ectodomain					531:540	the M protein ectodomain	517:540	the M protein ectodomain of infectious bronchitis coronavirus (IBV)	517:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	3	8	theme	protein	523:529	arg1	coronavirus					567:577	infectious bronchitis coronavirus	545:577	infectious bronchitis coronavirus (IBV)	545:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	3	9	theme	infectious	545:554	arg1	IBV					580:582	IBV	580:582	IBV	580:582	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	3	9	theme	infectious	545:554	arg1	coronavirus					567:577	infectious bronchitis coronavirus	545:577	infectious bronchitis coronavirus (IBV)	545:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	0	10	theme	stress	107:112	arg1	response					114:121	infectious bronchitis virus-induced ER stress response	68:121	infectious bronchitis virus-induced ER stress response	68:121	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	6	11	theme	proinflammatory	1126:1140	arg1	response					1142:1149	proinflammatory response	1126:1149	proinflammatory response	1126:1149	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	3	12	from	sites	508:512	arg1	ectodomain					531:540	the M protein ectodomain	517:540	the M protein ectodomain of infectious bronchitis coronavirus (IBV)	517:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	3	12	from	sites	508:512	arg1	coronavirus					567:577	infectious bronchitis coronavirus	545:577	infectious bronchitis coronavirus (IBV)	545:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	4	13	theme	viral	696:700	arg1	replication					702:712	viral replication	696:712	viral replication in culture cells	696:729	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	2	14	theme	protein	327:333	arg1	ectodomain					311:320	the N-terminal ectodomain	296:320	the N-terminal ectodomain of M protein	296:333	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	2	14	theme	protein	327:333	arg1	protein					327:333	M protein	325:333	M protein	325:333	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	6	15	dep	not	988:990	arg1	essential					992:1000	essential	992:1000	essential	992:1000	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	4	16	from	formation	682:690	arg1	cells					725:729	culture cells	717:729	culture cells	717:729	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	5	17	theme	stress	762:767	arg1	response					769:776	the ER stress response	755:776	the ER stress response	755:776	However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines.
30852271	6	18	theme	ER	1101:1102	arg1	stress					1104:1109	ER stress	1101:1109	ER stress	1101:1109	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	6	19	from	glycosylation	1019:1031	arg1	ectodomain					1054:1063	the IBV M protein ectodomain	1036:1063	the IBV M protein ectodomain	1036:1063	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	3	20	theme	M	521:521	arg1	ectodomain					531:540	the M protein ectodomain	517:540	the M protein ectodomain of infectious bronchitis coronavirus (IBV)	517:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	3	20	theme	M	521:521	arg1	coronavirus					567:577	infectious bronchitis coronavirus	545:577	infectious bronchitis coronavirus (IBV)	545:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	6	21	theme	protein	1046:1052	arg1	ectodomain					1054:1063	the IBV M protein ectodomain	1036:1063	the IBV M protein ectodomain	1036:1063	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	5	22	theme	response	769:776	arg1	activation					741:750	activation	741:750	activation of the ER stress response	741:776	However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines.
30852271	2	23	theme	M	325:325	arg1	protein					327:333	M protein	325:333	M protein	325:333	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	6	24	theme	M	1044:1044	arg1	ectodomain					1054:1063	the IBV M protein ectodomain	1036:1063	the IBV M protein ectodomain	1036:1063	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	0	25	theme	N-Linked	0:7	arg1	glycosylation					9:21	N-Linked glycosylation	0:21	N-Linked glycosylation of the membrane protein ectodomain	0:56	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	3	26	theme	coronavirus	567:577	arg1	ectodomain					531:540	the M protein ectodomain	517:540	the M protein ectodomain of infectious bronchitis coronavirus (IBV)	517:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	3	26	theme	coronavirus	567:577	arg1	coronavirus					567:577	infectious bronchitis coronavirus	545:577	infectious bronchitis coronavirus (IBV)	545:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	2	27	theme	precise	373:379	arg1	functions					381:389	its precise functions	369:389	its precise functions	369:389	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	4	28	theme	Dual	586:589	arg1	mutations					591:599	Dual mutations	586:599	Dual mutations at the two sites (N3D/N6D)	586:626	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	4	29	from	replication	702:712	arg1	cells					725:729	culture cells	717:729	culture cells	717:729	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	3	30	gly	glycosylation	470:482	arg2	sites					508:512	two predicted sites	494:512	two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV)	494:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	1	31	theme	abundant	197:204	arg1	protein					177:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	1	31	theme	abundant	197:204	arg1	protein					217:223	the most abundant structural protein	188:223	the most abundant structural protein playing a critical role in virion assembly	188:266	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	5	32	theme	pro-inflammatory	906:921	arg1	cytokines					923:931	pro-inflammatory cytokines	906:931	pro-inflammatory cytokines	906:931	However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines.
30852271	2	33	theme	N-terminal	300:309	arg1	ectodomain					311:320	the N-terminal ectodomain	296:320	the N-terminal ectodomain of M protein	296:333	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	2	33	theme	N-terminal	300:309	arg1	protein					327:333	M protein	325:333	M protein	325:333	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	4	34	from	sites	612:616	arg1	mutations					591:599	Dual mutations	586:599	Dual mutations at the two sites (N3D/N6D)	586:626	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	1	35	theme	structural	206:215	arg1	protein					177:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	1	35	theme	structural	206:215	arg1	protein					217:223	the most abundant structural protein	188:223	the most abundant structural protein playing a critical role in virion assembly	188:266	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	0	36	theme	protein	39:45	arg1	ectodomain					47:56	the membrane protein ectodomain	26:56	the membrane protein ectodomain	26:56	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	6	37	theme	IBV	1040:1042	arg1	ectodomain					1054:1063	the IBV M protein ectodomain	1036:1063	the IBV M protein ectodomain	1036:1063	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	0	38	theme	membrane	30:37	arg1	ectodomain					47:56	the membrane protein ectodomain	26:56	the membrane protein ectodomain	26:56	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	6	39	gly	glycosylation	1019:1031	arg1	IBV					1194:1196	IBV	1194:1196	IBV	1194:1196	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	6	39	gly	glycosylation	1019:1031	arg1	ectodomain					1054:1063	the IBV M protein ectodomain	1036:1063	the IBV M protein ectodomain	1036:1063	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	0	40	gly	glycosylation	9:21	arg1	ectodomain					47:56	the membrane protein ectodomain	26:56	the membrane protein ectodomain	26:56	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	5	41	theme	ER	759:760	arg1	response					769:776	the ER stress response	755:776	the ER stress response	755:776	However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines.
30852271	3	42	link	N-linked	461:468	arg1	glycosylation					470:482	N-linked glycosylation	461:482	N-linked glycosylation	461:482	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	5	43	theme	apoptosis	870:878	arg1	level					861:865	a lower level	853:865	a lower level of apoptosis	853:878	However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines.
30852271	0	44	theme	ectodomain	47:56	arg1	glycosylation					9:21	N-Linked glycosylation	0:21	N-Linked glycosylation of the membrane protein ectodomain	0:56	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	6	45	theme	IBV	1194:1196	arg1	pathogenesis					1178:1189	the pathogenesis	1174:1189	the pathogenesis of IBV	1174:1196	Taken together, this study demonstrates that although not essential for replication, glycosylation in the IBV M protein ectodomain plays important roles in activating ER stress, apoptosis and proinflammatory response, and may contribute to the pathogenesis of IBV.
30852271	4	46	theme	particle	673:680	arg1	formation					682:690	virus-like particle formation	662:690	virus-like particle formation	662:690	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	3	47	theme	bronchitis	556:565	arg1	IBV					580:582	IBV	580:582	IBV	580:582	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	3	47	theme	bronchitis	556:565	arg1	coronavirus					567:577	infectious bronchitis coronavirus	545:577	infectious bronchitis coronavirus (IBV)	545:583	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	2	48	theme	Previous	269:276	arg1	studies					278:284	Previous studies	269:284	Previous studies	269:284	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	3	49	theme	N-linked	461:468	arg1	glycosylation					470:482	N-linked glycosylation	461:482	N-linked glycosylation	461:482	In this study, we confirm that N-linked glycosylation occurs at two predicted sites in the M protein ectodomain of infectious bronchitis coronavirus (IBV).
30852271	5	50	theme	cytokines	923:931	arg1	production					892:901	production	892:901	production of pro-inflammatory cytokines	892:931	However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines.
30852271	4	51	theme	culture	717:723	arg1	cells					725:729	culture cells	717:729	culture cells	717:729	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30852271	1	52	theme	Coronavirus	152:162	arg1	protein					177:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	1	52	theme	Coronavirus	152:162	arg1	protein					217:223	the most abundant structural protein	188:223	the most abundant structural protein playing a critical role in virion assembly	188:266	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	2	53	mod	modified	338:345	arg1	ectodomain					311:320	the N-terminal ectodomain	296:320	the N-terminal ectodomain of M protein	296:333	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	2	53	mod	modified	338:345	arg1	protein					327:333	M protein	325:333	M protein	325:333	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	2	53	mod	modified	338:345	arg3	glycosylation					350:362	glycosylation	350:362	glycosylation	350:362	Previous studies show that the N-terminal ectodomain of M protein is modified by glycosylation, but its precise functions are yet to be thoroughly investigated.
30852271	1	54	theme	critical	235:242	arg1	role					244:247	a critical role	233:247	a critical role	233:247	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	0	55	theme	bronchitis	79:88	arg1	response					114:121	infectious bronchitis virus-induced ER stress response	68:121	infectious bronchitis virus-induced ER stress response	68:121	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	5	56	theme	lower	855:859	arg1	level					861:865	a lower level	853:865	a lower level of apoptosis	853:878	However, activation of the ER stress response was significantly reduced in cells infected with rN3D/N6D, correlated with a lower level of apoptosis and reduced production of pro-inflammatory cytokines.
30852271	1	57	theme	membrane	164:171	arg1	protein					177:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein	152:183	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	1	57	theme	membrane	164:171	arg1	protein					217:223	the most abundant structural protein	188:223	the most abundant structural protein playing a critical role in virion assembly	188:266	Coronavirus membrane (M) protein is the most abundant structural protein playing a critical role in virion assembly.
30852271	0	58	theme	infectious	68:77	arg1	response					114:121	infectious bronchitis virus-induced ER stress response	68:121	infectious bronchitis virus-induced ER stress response	68:121	N-Linked glycosylation of the membrane protein ectodomain regulates infectious bronchitis virus-induced ER stress response, apoptosis and pathogenesis.
30852271	4	59	theme	particle	643:650	arg1	assembly					652:659	particle assembly	643:659	particle assembly	643:659	Dual mutations at the two sites (N3D/N6D) did not affect particle assembly, virus-like particle formation and viral replication in culture cells.
30683699	6	0	theme	N-terminal	1351:1360	arg1	sequon					1369:1374	the N-terminal Asn221 sequon	1347:1374	the N-terminal Asn221 sequon	1347:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	5	1	theme	engineering	1213:1223	arg1	approaches					1225:1234	Ab engineering approaches	1210:1234	Ab engineering approaches	1210:1234	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
30683699	3	2	gly	sialylated	625:634	arg1	Fc					636:637	sialylated Fc	625:637	sialylated Fc	625:637	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	0	3	theme	Region	76:81	arg1	Interactions					53:64	Interactions	53:64	Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors	53:136	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	6	4	theme	sialylated	1316:1325	arg1	glycans					1327:1333	complex sialylated glycans	1308:1333	complex sialylated glycans attached to the N-terminal Asn221 sequon	1308:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	2	5	theme	retention	567:575	arg1	times					577:581	longer serum retention times	554:581	longer serum retention times advantageous for therapy	554:606	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	6	6	attach	attached	1335:1342	arg2	glycans					1327:1333	complex sialylated glycans	1308:1333	complex sialylated glycans attached to the N-terminal Asn221 sequon	1308:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	6	6	attach	attached	1335:1342	arg1	sequon					1369:1374	the N-terminal Asn221 sequon	1347:1374	the N-terminal Asn221 sequon	1347:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	3	7	theme	carbohydrate	834:845	arg1	interface					847:855	the protein-Asn297 carbohydrate interface	815:855	the protein-Asn297 carbohydrate interface	815:855	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	0	8	theme	IgG1	92:95	arg1	Monomers					97:104	Human IgG1 Monomers	86:104	Human IgG1 Monomers with Glycan-Dependent Receptors	86:136	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	1	9	dep	binding	279:285	arg1	the					266:268	the	266:268	the	266:268	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	2	10	theme	serum	561:565	arg1	times					577:581	longer serum retention times	554:581	longer serum retention times advantageous for therapy	554:606	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	4	11	theme	mutants	1007:1013	arg1	portfolio					994:1002	a portfolio	992:1002	a portfolio of mutants with tailored effector functions	992:1046	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	4	12	with	mutants	1007:1013	arg1	functions					1038:1046	tailored effector functions	1020:1046	tailored effector functions	1020:1046	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	0	13	theme	Human	86:90	arg1	Monomers					97:104	Human IgG1 Monomers	86:104	Human IgG1 Monomers with Glycan-Dependent Receptors	86:136	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	3	14	theme	glycosylation	696:708	arg1	site					710:713	the unique N-linked glycosylation site	676:713	the unique N-linked glycosylation site at Asn297	676:723	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	2	15	theme	longer	554:559	arg1	times					577:581	longer serum retention times	554:581	longer serum retention times advantageous for therapy	554:606	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	5	16	theme	human	1131:1135	arg1	Fcγ					1137:1139	low-affinity inhibitory human Fcγ and glycan receptors	1107:1160	Fcγ	1137:1139	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
30683699	3	17	theme	Fc	636:637	arg1	efficacy					613:620	The efficacy	609:620	The efficacy of sialylated Fc	609:637	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	6	18	theme	human	1464:1468	arg1	erythrocytes					1470:1481	human erythrocytes	1464:1481	human erythrocytes	1464:1481	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	6	19	theme	virus	1392:1396	arg1	hemagglutinin					1398:1410	influenza virus hemagglutinin	1382:1410	influenza virus hemagglutinin	1382:1410	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	3	20	link	N-linked	687:694	arg1	site					710:713	the unique N-linked glycosylation site	676:713	the unique N-linked glycosylation site at Asn297	676:723	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	0	21	theme	Monomers	97:104	arg1	Region					76:81	the Fc Region	69:81	the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors	69:136	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	3	22	theme	unique	680:685	arg1	site					710:713	the unique N-linked glycosylation site	676:713	the unique N-linked glycosylation site at Asn297	676:723	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	3	23	theme	Fc	797:798	arg1	mutagenesis					778:788	mutagenesis	778:788	mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface	778:855	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	6	24	theme	influenza	1426:1434	arg1	agglutination					1447:1459	influenza A-mediated agglutination	1426:1459	influenza A-mediated agglutination of human erythrocytes	1426:1481	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	1	25	gly	deglycosylation	338:352	arg1	sequon					396:401	the unique Asn297 N-X-(T/S) sequon	368:401	the unique Asn297 N-X-(T/S) sequon	368:401	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	2	26	theme	Fcs	420:422	arg1	population					406:415	A population	404:415	A population of Fcs bearing sialylated glycans	404:449	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	3	27	theme	N-linked	687:694	arg1	site					710:713	the unique N-linked glycosylation site	676:713	the unique N-linked glycosylation site at Asn297	676:723	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	0	28	with	Monomers	97:104	arg1	Receptors					128:136	Glycan-Dependent Receptors	111:136	Glycan-Dependent Receptors	111:136	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	5	29	theme	inhibitory	1120:1129	arg1	Fcγ					1137:1139	low-affinity inhibitory human Fcγ and glycan receptors	1107:1160	Fcγ	1137:1139	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
30683699	6	30	theme	influenza	1382:1390	arg1	hemagglutinin					1398:1410	influenza virus hemagglutinin	1382:1410	influenza virus hemagglutinin	1382:1410	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	4	31	theme	Fc	977:978	arg1	body					965:968	the body	961:968	the body of the Fc to generate a portfolio of mutants with tailored effector functions	961:1046	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	1	32	theme	receptor	270:277	arg1	binding					279:285	receptor binding	270:285	receptor binding	270:285	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	2	33	theme	advantageous	583:594	arg1	times					577:581	longer serum retention times	554:581	longer serum retention times advantageous for therapy	554:606	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	1	34	theme	therapeutic	193:203	arg1	applications					205:216	therapeutic applications	193:216	therapeutic applications in which the Fc of IgG is critically important	193:263	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	0	35	theme	Hinge	24:28	arg1	Glycosylation					30:42	N-Terminal Hinge Glycosylation	13:42	N-Terminal Hinge Glycosylation	13:42	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	3	36	gly	glycosylation	696:708	arg2	site					710:713	the unique N-linked glycosylation site	676:713	the unique N-linked glycosylation site at Asn297	676:723	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	3	36	gly	glycosylation	696:708	arg2	Asn297					718:723	Asn297	718:723	Asn297	718:723	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	6	37	theme	complex	1308:1314	arg1	glycans					1327:1333	complex sialylated glycans	1308:1333	complex sialylated glycans attached to the N-terminal Asn221 sequon	1308:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	3	38	theme	sialylated	625:634	arg1	Fc					636:637	sialylated Fc	625:637	sialylated Fc	625:637	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	0	39	theme	N-Terminal	13:22	arg1	Glycosylation					30:42	N-Terminal Hinge Glycosylation	13:42	N-Terminal Hinge Glycosylation	13:42	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	0	40	theme	Glycan-Dependent	111:126	arg1	Receptors					128:136	Glycan-Dependent Receptors	111:136	Glycan-Dependent Receptors	111:136	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	1	41	theme	unique	372:377	arg1	sequon					396:401	the unique Asn297 N-X-(T/S) sequon	368:401	the unique Asn297 N-X-(T/S) sequon	368:401	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	4	42	theme	attachment	939:948	arg1	sites					950:954	or deleting N-linked attachment sites	918:954	sites	950:954	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	5	43	theme	glycan	1145:1150	arg1	receptors					1152:1160	low-affinity inhibitory human Fcγ and glycan receptors	1107:1160	receptors	1152:1160	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
30683699	1	44	theme	functional	291:300	arg1	properties					302:311	functional properties	291:311	functional properties	291:311	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	2	45	theme	high	514:517	arg1	levels					519:524	high levels	514:524	high levels of sialylation	514:539	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	1	46	theme	Asn297	379:384	arg1	sequon					396:401	the unique Asn297 N-X-(T/S) sequon	368:401	the unique Asn297 N-X-(T/S) sequon	368:401	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	4	47	theme	alternative	884:894	arg1	approach					896:903	an alternative approach	881:903	an alternative approach	881:903	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	0	48	theme	Glycosylation	30:42	arg1	Insertion					0:8	Insertion	0:8	Insertion of N-Terminal Hinge Glycosylation	0:42	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	1	49	from	important	255:263	arg1	applications					205:216	therapeutic applications	193:216	therapeutic applications in which the Fc of IgG is critically important	193:263	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	1	50	theme	N-X-	386:389	arg1	sequon					396:401	the unique Asn297 N-X-(T/S) sequon	368:401	the unique Asn297 N-X-(T/S) sequon	368:401	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	3	51	theme	chemical	741:748	arg1	methods					764:770	chemical and enzymatic methods	741:770	chemical and enzymatic methods	741:770	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	2	52	theme	sialylated	432:441	arg1	glycans					443:449	sialylated glycans	432:449	sialylated glycans	432:449	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	3	53	theme	enzymatic	754:762	arg1	methods					764:770	chemical and enzymatic methods	741:770	chemical and enzymatic methods	741:770	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	6	54	theme	IgG1	1279:1282	arg1	Fc					1284:1285	IgG1 Fc	1279:1285	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon	1275:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	6	55	theme	Asn221	1362:1367	arg1	sequon					1369:1374	the N-terminal Asn221 sequon	1347:1374	the N-terminal Asn221 sequon	1347:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	6	56	gly	sialylated	1316:1325	arg1	glycans					1327:1333	complex sialylated glycans	1308:1333	complex sialylated glycans attached to the N-terminal Asn221 sequon	1308:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	3	57	from	Asn297	718:723	arg1	site					710:713	the unique N-linked glycosylation site	676:713	the unique N-linked glycosylation site at Asn297	676:723	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	4	58	link	N-linked	930:937	arg1	sites					950:954	or deleting N-linked attachment sites	918:954	sites	950:954	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	5	59	theme	low-affinity	1107:1118	arg1	Fcγ					1137:1139	low-affinity inhibitory human Fcγ and glycan receptors	1107:1160	Fcγ	1137:1139	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
30683699	4	60	dep	sites	950:954	arg1	deleting					921:928	deleting	921:928	deleting	921:928	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	1	61	theme	T/S	391:393	arg1	sequon					396:401	the unique Asn297 N-X-(T/S) sequon	368:401	the unique Asn297 N-X-(T/S) sequon	368:401	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	2	62	gly	sialylated	432:441	arg1	glycans					443:449	sialylated glycans	432:449	sialylated glycans	432:449	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	1	63	from	applications	205:216	arg1	important					255:263	important	255:263	important	255:263	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	1	63	from	applications	205:216	arg1	Fc					231:232	the Fc	227:232	the Fc of IgG	227:239	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	4	64	theme	effector	1029:1036	arg1	functions					1038:1046	tailored effector functions	1020:1046	tailored effector functions	1020:1046	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	1	65	theme	Fc	320:321	arg1	binding					279:285	receptor binding	270:285	receptor binding	270:285	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	1	65	theme	Fc	320:321	arg1	properties					302:311	functional properties	291:311	functional properties	291:311	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	0	66	theme	Influenza	173:181	arg1	Virus					183:187	the Influenza Virus	169:187	the Influenza Virus	169:187	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	3	67	theme	protein-Asn297	819:832	arg1	interface					847:855	the protein-Asn297 carbohydrate interface	815:855	the protein-Asn297 carbohydrate interface	815:855	The efficacy of sialylated Fc has generated an incentive to modify the unique N-linked glycosylation site at Asn297, either through chemical and enzymatic methods or by mutagenesis of the Fc, that disrupts the protein-Asn297 carbohydrate interface.
30683699	6	68	theme	Fc	1284:1285	arg1	fragments					1287:1295	The IgG1 Fc fragments	1275:1295	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon	1275:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	2	69	theme	sialylation	529:539	arg1	levels					519:524	high levels	514:524	high levels of sialylation	514:539	A population of Fcs bearing sialylated glycans has been identified as contributing to this functionality, and high levels of sialylation also lead to longer serum retention times advantageous for therapy.
30683699	1	70	theme	sequon	396:401	arg1	removal					357:363	removal	357:363	removal of the unique Asn297 N-X-(T/S) sequon	357:401	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	1	70	theme	sequon	396:401	arg1	deglycosylation					338:352	deglycosylation	338:352	deglycosylation	338:352	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	6	71	contain	containing	1297:1306	arg1	fragments					1287:1295	The IgG1 Fc fragments	1275:1295	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon	1275:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	6	71	contain	containing	1297:1306	arg2	glycans					1327:1333	complex sialylated glycans	1308:1333	complex sialylated glycans attached to the N-terminal Asn221 sequon	1308:1374	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	0	72	theme	Fc	73:74	arg1	Region					76:81	the Fc Region	69:81	the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors	69:136	Insertion of N-Terminal Hinge Glycosylation Enhances Interactions of the Fc Region of Human IgG1 Monomers with Glycan-Dependent Receptors and Blocks Hemagglutination by the Influenza Virus.
30683699	5	73	with	mutants	1074:1080	arg1	binding					1096:1102	enhanced binding	1087:1102	enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease	1087:1272	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
30683699	5	74	theme	enhanced	1087:1094	arg1	binding					1096:1102	enhanced binding	1087:1102	enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease	1087:1272	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
30683699	6	75	theme	erythrocytes	1470:1481	arg1	agglutination					1447:1459	influenza A-mediated agglutination	1426:1459	influenza A-mediated agglutination of human erythrocytes	1426:1481	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	4	76	theme	tailored	1020:1027	arg1	functions					1038:1046	tailored effector functions	1020:1046	tailored effector functions	1020:1046	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	1	77	theme	IgG	237:239	arg1	important					255:263	important	255:263	important	255:263	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	1	77	theme	IgG	237:239	arg1	Fc					231:232	the Fc	227:232	the Fc of IgG	227:239	In therapeutic applications in which the Fc of IgG is critically important, the receptor binding and functional properties of the Fc are lost after deglycosylation or removal of the unique Asn297 N-X-(T/S) sequon.
30683699	4	78	theme	N-linked	930:937	arg1	sites					950:954	or deleting N-linked attachment sites	918:954	sites	950:954	In this study, we took an alternative approach by inserting or deleting N-linked attachment sites into the body of the Fc to generate a portfolio of mutants with tailored effector functions.
30683699	6	79	theme	A-mediated	1436:1445	arg1	agglutination					1447:1459	influenza A-mediated agglutination	1426:1459	influenza A-mediated agglutination of human erythrocytes	1426:1481	The IgG1 Fc fragments containing complex sialylated glycans attached to the N-terminal Asn221 sequon bound influenza virus hemagglutinin and disrupted influenza A-mediated agglutination of human erythrocytes.
30683699	5	80	theme	Ab	1210:1211	arg1	approaches					1225:1234	Ab engineering approaches	1210:1234	Ab engineering approaches	1210:1234	For example, we describe mutants with enhanced binding to low-affinity inhibitory human Fcγ and glycan receptors that may be usefully incorporated into existing Ab engineering approaches to treat or vaccinate against disease.
29946357	14	0	theme	large	2747:2751	arg1	number					2753:2758	a large number	2745:2758	a large number	2745:2758	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	10	1	theme	targeted	1848:1855	arg1	approach					1871:1878	A targeted metasecretome approach	1846:1878	A targeted metasecretome approach	1846:1878	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	9	2	theme	fungal	1795:1800	arg1	species					1802:1808	fungal species	1795:1808	fungal species that were present in low abundance	1795:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	3	3	theme	plant	607:611	arg1	materials					613:621	breakdown plant materials	597:621	breakdown plant materials	597:621	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	13	4	theme	degrading	2524:2532	arg1	enzymes					2534:2540	lignocellulose degrading enzymes	2509:2540	lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks	2509:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	6	5	theme	feedstocks	1258:1267	arg1	pre-treatment					1241:1253	industrial pre-treatment	1230:1253	industrial pre-treatment of feedstocks	1230:1267	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
29946357	12	6	theme	ssNMR	2340:2344	arg1	measurements					2346:2357	FTIR and ssNMR measurements	2331:2357	FTIR and ssNMR measurements	2331:2357	The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.
29946357	11	7	theme	lignocellulose	2203:2216	arg1	degradation					2218:2228	lignocellulose degradation	2203:2228	lignocellulose degradation	2203:2228	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	1	8	theme	carbon	182:187	arg1	forms					167:171	the most abundant forms	149:171	the most abundant forms of fixed carbon in the biosphere	149:204	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	2	9	theme	fungal	320:325	arg1	effective					351:359	effective	351:359	effective	351:359	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	2	9	theme	fungal	320:325	arg1	species					327:333	a single fungal species	311:333	a single fungal species	311:333	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	9	10	theme	low	1831:1833	arg1	abundance					1835:1843	low abundance	1831:1843	low abundance	1831:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	12	11	theme	FTIR	2331:2334	arg1	measurements					2346:2357	FTIR and ssNMR measurements	2331:2357	FTIR and ssNMR measurements	2331:2357	The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.
29946357	9	12	located	present	1820:1826	arg2	species					1802:1808	fungal species	1795:1808	fungal species that were present in low abundance	1795:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	9	12	located	present	1820:1826	arg1	abundance					1835:1843	low abundance	1831:1843	low abundance	1831:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	8	13	theme	relative	1572:1579	arg1	abundance					1581:1589	high relative abundance	1567:1589	high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera	1567:1642	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	11	14	theme	cellulases	2131:2140	arg1	modules					2183:2189	carbohydrate-binding modules	2162:2189	carbohydrate-binding modules	2162:2189	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	11	14	theme	cellulases	2131:2140	arg1	hemicellulases					2143:2156	hemicellulases	2143:2156	hemicellulases	2143:2156	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	11	14	theme	cellulases	2131:2140	arg1	array					2111:2115	a wide array	2104:2115	a wide array of hydrolytic cellulases	2104:2140	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	1	15	from	biosphere	196:204	arg1	forms					167:171	the most abundant forms	149:171	the most abundant forms of fixed carbon in the biosphere	149:204	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	13	16	theme	enzymes	2534:2540	arg1	number					2499:2504	a large number	2491:2504	a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks	2491:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	7	17	theme	microbial	1445:1453	arg1	enrichment					1455:1464	microbial enrichment	1445:1464	microbial enrichment	1445:1464	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	12	18	theme	biomass	2299:2305	arg1	composition					2307:2317	the biomass composition	2295:2317	the biomass composition observed by FTIR and ssNMR measurements	2295:2357	The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.
29946357	3	19	theme	enzymes	674:680	arg1	myriad					664:669	a myriad	662:669	a myriad of enzymes to perform "community-level" metabolism of lignocellulose	662:738	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	14	20	theme	lignocellulose	2838:2851	arg1	degradation					2853:2863	community-based lignocellulose degradation	2822:2863	community-based lignocellulose degradation	2822:2863	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	4	21	theme	Single-species	741:754	arg1	approaches					756:765	Single-species approaches	741:765	Single-species approaches	741:765	Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.
29946357	7	22	theme	sequenced	1322:1330	arg1	genes					1367:1371	sequenced bacterial and eukaryotic ribosomal genes	1322:1371	sequenced bacterial and eukaryotic ribosomal genes	1322:1371	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	10	23	theme	numerous	1976:1983	arg1	enzymes					2005:2011	numerous carbohydrate-active enzymes	1976:2011	numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant	1976:2087	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	9	24	theme	eukaryotic	1649:1658	arg1	members					1660:1666	The eukaryotic members	1645:1666	The eukaryotic members of the community	1645:1683	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	8	25	theme	Leadbetterella	1616:1629	arg1	abundance					1581:1589	high relative abundance	1567:1589	high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera	1567:1642	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	8	25	theme	Leadbetterella	1616:1629	arg1	dominance					1517:1525	dominance	1517:1525	dominance of Bacteroidetes and Proteobacteria	1517:1561	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	1	26	from	forms	167:171	arg1	biosphere					196:204	the biosphere	192:204	the biosphere	192:204	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	13	27	theme	lignocellulose	2509:2522	arg1	enzymes					2534:2540	lignocellulose degrading enzymes	2509:2540	lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks	2509:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	6	28	theme	selected	1061:1068	arg1	points					1075:1080	selected time points	1061:1080	selected time points	1061:1080	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
29946357	8	29	theme	Truepera	1635:1642	arg1	abundance					1581:1589	high relative abundance	1567:1589	high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera	1567:1642	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	8	29	theme	Truepera	1635:1642	arg1	dominance					1517:1525	dominance	1517:1525	dominance of Bacteroidetes and Proteobacteria	1517:1561	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	4	30	theme	lignocellulose	819:832	arg1	degradation					834:844	lignocellulose degradation	819:844	lignocellulose degradation	819:844	Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.
29946357	7	31	theme	community	1302:1310	arg1	composition					1283:1293	Phylogenetic composition	1270:1293	Phylogenetic composition	1270:1293	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	9	32	theme	community	1675:1683	arg1	members					1660:1666	The eukaryotic members	1645:1666	The eukaryotic members of the community	1645:1683	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	9	33	from	abundance	1835:1843	arg1	present					1820:1826	present	1820:1826	present	1820:1826	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	3	34	theme	degradation	475:485	arg1	mechanisms					446:455	the enzymatic mechanisms	432:455	the enzymatic mechanisms of lignocellulose degradation	432:485	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	8	35	theme	Taxonomic	1467:1475	arg1	affiliation					1477:1487	Taxonomic affiliation	1467:1487	Taxonomic affiliation of bacterial species	1467:1508	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	2	36	theme	biomass	402:408	arg1	pre-treatments					410:423	biomass pre-treatments	402:423	biomass pre-treatments	402:423	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	7	37	theme	Phylogenetic	1270:1281	arg1	composition					1283:1293	Phylogenetic composition	1270:1293	Phylogenetic composition	1270:1293	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	9	38	theme	peritrich	1702:1710	arg1	ciliates					1712:1719	peritrich ciliates	1702:1719	peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance	1702:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	10	39	theme	biomass-bound	2032:2044	arg1	fractions					2046:2054	the biomass-bound fractions	2028:2054	the biomass-bound fractions	2028:2054	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	10	40	theme	carbohydrate-active	1985:2003	arg1	enzymes					2005:2011	numerous carbohydrate-active enzymes	1976:2011	numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant	1976:2087	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	4	41	theme	commercial	881:890	arg1	processes					892:900	optimizing commercial processes	870:900	optimizing commercial processes	870:900	Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.
29946357	5	42	theme	wheat	1023:1027	arg1	compost					1035:1041	wheat straw compost	1023:1041	wheat straw compost	1023:1041	RESULTS Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost.
29946357	3	43	theme	enzymatic	436:444	arg1	mechanisms					446:455	the enzymatic mechanisms	432:455	the enzymatic mechanisms of lignocellulose degradation	432:485	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	3	44	theme	community-level	694:708	arg1	metabolism					711:720	"community-level" metabolism	693:720	"community-level" metabolism of lignocellulose	693:738	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	8	45	theme	species	1502:1508	arg1	affiliation					1477:1487	Taxonomic affiliation	1467:1487	Taxonomic affiliation of bacterial species	1467:1508	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	0	46	theme	lignocellulose	34:47	arg1	degradation					49:59	lignocellulose degradation	34:59	lignocellulose degradation	34:59	Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies.
29946357	6	47	theme	multi-omics	1100:1110	arg1	analysis					1112:1119	multi-omics analysis	1100:1119	multi-omics analysis	1100:1119	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
29946357	0	48	theme	microbial	66:74	arg1	community					76:84	a microbial community	64:84	a microbial community using multi-omics studies	64:110	Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies.
29946357	14	49	theme	expected	2688:2695	arg1	enzymes					2717:2723	the expected carbohydrate-active enzymes	2684:2723	the expected carbohydrate-active enzymes	2684:2723	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	3	50	theme	microbial	535:543	arg1	species					545:551	individual microbial species	524:551	individual microbial species	524:551	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	13	51	theme	plant-based	2645:2655	arg1	feedstocks					2657:2666	plant-based feedstocks	2645:2666	plant-based feedstocks	2645:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	11	52	theme	carbohydrate-binding	2162:2181	arg1	array					2111:2115	a wide array	2104:2115	a wide array of hydrolytic cellulases	2104:2140	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	11	52	theme	carbohydrate-binding	2162:2181	arg1	modules					2183:2189	carbohydrate-binding modules	2162:2189	carbohydrate-binding modules	2162:2189	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	3	53	theme	lignocellulose	725:738	arg1	metabolism					711:720	"community-level" metabolism	693:720	"community-level" metabolism of lignocellulose	693:738	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	8	54	theme	Bacteroidetes	1530:1542	arg1	abundance					1581:1589	high relative abundance	1567:1589	high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera	1567:1642	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	8	54	theme	Bacteroidetes	1530:1542	arg1	dominance					1517:1525	dominance	1517:1525	dominance of Bacteroidetes and Proteobacteria	1517:1561	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	4	55	theme	optimizing	870:879	arg1	processes					892:900	optimizing commercial processes	870:900	optimizing commercial processes	870:900	Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.
29946357	13	56	theme	mass	2389:2392	arg1	proteomics					2413:2422	mass spectrometry-based proteomics	2389:2422	mass spectrometry-based proteomics coupled with metatranscriptomics	2389:2455	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	14	57	theme	unknown	2763:2769	arg1	proteins					2771:2778	unknown proteins	2763:2778	unknown proteins	2763:2778	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	13	58	theme	enzyme	2607:2612	arg1	cocktails					2614:2622	improved enzyme cocktails	2598:2622	improved enzyme cocktails for the treatment of plant-based feedstocks	2598:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	5	59	theme	wheat	962:966	arg1	straw					968:972	wheat straw	962:972	wheat straw	962:972	RESULTS Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost.
29946357	11	60	theme	wide	2106:2109	arg1	modules					2183:2189	carbohydrate-binding modules	2162:2189	carbohydrate-binding modules	2162:2189	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	11	60	theme	wide	2106:2109	arg1	hemicellulases					2143:2156	hemicellulases	2143:2156	hemicellulases	2143:2156	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	11	60	theme	wide	2106:2109	arg1	array					2111:2115	a wide array	2104:2115	a wide array of hydrolytic cellulases	2104:2140	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	8	61	theme	Proteobacteria	1548:1561	arg1	abundance					1581:1589	high relative abundance	1567:1589	high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera	1567:1642	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	8	61	theme	Proteobacteria	1548:1561	arg1	dominance					1517:1525	dominance	1517:1525	dominance of Bacteroidetes and Proteobacteria	1517:1561	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	3	62	theme	microbial	558:566	arg1	species					637:643	species	637:643	species	637:643	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	3	62	theme	microbial	558:566	arg1	rich					645:648	rich	645:648	rich	645:648	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	3	62	theme	microbial	558:566	arg1	communities					568:578	the microbial communities	554:578	the microbial communities that efficiently breakdown plant materials in nature	554:631	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	3	63	dep	rich	645:648	arg1	species					637:643	species	637:643	species	637:643	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	3	63	dep	rich	645:648	arg1	rich					645:648	rich	645:648	rich	645:648	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	3	63	dep	rich	645:648	arg1	communities					568:578	the microbial communities	554:578	the microbial communities that efficiently breakdown plant materials in nature	554:631	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	13	64	theme	proteomics	2413:2422	arg1	combination					2374:2384	A combination	2372:2384	A combination of mass spectrometry-based proteomics coupled with metatranscriptomics	2372:2455	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	7	65	theme	ribosomal	1357:1365	arg1	genes					1367:1371	sequenced bacterial and eukaryotic ribosomal genes	1322:1371	sequenced bacterial and eukaryotic ribosomal genes	1322:1371	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	13	66	theme	number	2499:2504	arg1	identification					2473:2486	the identification	2469:2486	the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks	2469:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	10	67	theme	enzymes	2005:2011	arg1	presence					1964:1971	the presence	1960:1971	the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant	1960:2087	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	10	68	theme	metasecretome	1857:1869	arg1	approach					1871:1878	A targeted metasecretome approach	1846:1878	A targeted metasecretome approach	1846:1878	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	6	69	theme	microbial	1153:1161	arg1	mechanisms					1163:1172	new microbial mechanisms	1149:1172	new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks	1149:1267	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
29946357	3	70	theme	breakdown	597:605	arg1	materials					613:621	breakdown plant materials	597:621	breakdown plant materials	597:621	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	5	71	theme	straw	968:972	arg1	degradation					947:957	the microbial degradation	933:957	the microbial degradation of wheat straw	933:972	RESULTS Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost.
29946357	10	72	theme	metatranscriptomics	1894:1912	arg1	analysis					1914:1921	metatranscriptomics analysis	1894:1921	metatranscriptomics analysis	1894:1921	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	1	73	theme	fixed	176:180	arg1	carbon					182:187	fixed carbon	176:187	fixed carbon in the biosphere	176:204	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	2	74	theme	industrial	215:224	arg1	approaches					226:235	Current industrial approaches	207:235	Current industrial approaches to the degradation of lignocellulose	207:272	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	5	75	theme	microbial	937:945	arg1	degradation					947:957	the microbial degradation	933:957	the microbial degradation of wheat straw	933:972	RESULTS Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost.
29946357	9	76	from	present	1820:1826	arg1	abundance					1835:1843	low abundance	1831:1843	low abundance	1831:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	6	77	theme	industrial	1230:1239	arg1	pre-treatment					1241:1253	industrial pre-treatment	1230:1253	industrial pre-treatment of feedstocks	1230:1267	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
29946357	2	78	theme	single	313:318	arg1	effective					351:359	effective	351:359	effective	351:359	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	2	78	theme	single	313:318	arg1	species					327:333	a single fungal species	311:333	a single fungal species	311:333	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	8	79	theme	high	1567:1570	arg1	abundance					1581:1589	high relative abundance	1567:1589	high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera	1567:1642	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	14	80	theme	crucial	2806:2812	arg1	role					2814:2817	a crucial role	2804:2817	a crucial role	2804:2817	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	11	81	theme	hydrolytic	2120:2129	arg1	cellulases					2131:2140	hydrolytic cellulases	2120:2140	hydrolytic cellulases	2120:2140	This revealed a wide array of hydrolytic cellulases, hemicellulases and carbohydrate-binding modules involved in lignocellulose degradation.
29946357	5	82	theme	liquid	977:982	arg1	cultures					984:991	liquid cultures	977:991	liquid cultures that had been inoculated with wheat straw compost	977:1041	RESULTS Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost.
29946357	2	83	theme	Current	207:213	arg1	approaches					226:235	Current industrial approaches	207:235	Current industrial approaches to the degradation of lignocellulose	207:272	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	3	84	from	materials	613:621	arg1	nature					626:631	nature	626:631	nature	626:631	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	2	85	theme	enzyme	281:286	arg1	mixtures					288:295	enzyme mixtures	281:295	enzyme mixtures	281:295	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	12	86	from	changes	2284:2290	arg1	composition					2307:2317	the biomass composition	2295:2317	the biomass composition observed by FTIR and ssNMR measurements	2295:2357	The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.
29946357	3	87	from	detail	514:519	arg1	species					545:551	individual microbial species	524:551	individual microbial species	524:551	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	13	88	dep	CONCLUSIONS	2360:2370	arg1	enabled					2461:2467	enabled	2461:2467	has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks	2457:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	2	89	theme	lignocellulose	259:272	arg1	degradation					244:254	the degradation	240:254	the degradation of lignocellulose	240:272	Current industrial approaches to the degradation of lignocellulose employ enzyme mixtures, usually from a single fungal species, which are only effective in hydrolyzing polysaccharides following biomass pre-treatments.
29946357	13	90	theme	large	2493:2497	arg1	number					2499:2504	a large number	2491:2504	a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks	2491:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	14	91	theme	community-based	2822:2836	arg1	degradation					2853:2863	community-based lignocellulose degradation	2822:2863	community-based lignocellulose degradation	2822:2863	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	12	92	theme	activities	2255:2264	arg1	expression					2235:2244	The expression	2231:2244	The expression of these activities	2231:2264	The expression of these activities correlated to the changes in the biomass composition observed by FTIR and ssNMR measurements.
29946357	0	93	theme	multi-omics	92:102	arg1	studies					104:110	multi-omics studies	92:110	multi-omics studies	92:110	Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies.
29946357	1	94	from	carbon	182:187	arg1	biosphere					196:204	the biosphere	192:204	the biosphere	192:204	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	1	95	theme	forms	167:171	arg1	forms					167:171	the most abundant forms	149:171	the most abundant forms of fixed carbon in the biosphere	149:204	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	1	95	theme	forms	167:171	arg1	one					142:144	one	142:144	one	142:144	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	6	96	theme	time	1070:1073	arg1	points					1075:1080	selected time points	1061:1080	selected time points	1061:1080	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
29946357	5	97	theme	straw	1029:1033	arg1	compost					1035:1041	wheat straw compost	1023:1041	wheat straw compost	1023:1041	RESULTS Here, we investigated the microbial degradation of wheat straw in liquid cultures that had been inoculated with wheat straw compost.
29946357	6	98	theme	new	1149:1151	arg1	mechanisms					1163:1172	new microbial mechanisms	1149:1172	new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks	1149:1267	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
29946357	4	99	theme	degradation	834:844	arg1	aspects					808:814	important aspects	798:814	important aspects of lignocellulose degradation that will be central to optimizing commercial processes	798:900	Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.
29946357	0	100	theme	functional	9:18	arg1	diversity					20:28	functional diversity	9:28	functional diversity for lignocellulose degradation	9:59	Defining functional diversity for lignocellulose degradation in a microbial community using multi-omics studies.
29946357	13	101	theme	feedstocks	2657:2666	arg1	treatment					2632:2640	the treatment	2628:2640	the treatment of plant-based feedstocks	2628:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	3	102	theme	lignocellulose	460:473	arg1	degradation					475:485	lignocellulose degradation	460:485	lignocellulose degradation	460:485	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	13	103	theme	cocktails	2614:2622	arg1	development					2583:2593	the development	2579:2593	the development of improved enzyme cocktails for the treatment of plant-based feedstocks	2579:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	1	104	theme	BACKGROUND	113:122	arg1	Lignocellulose					124:137	BACKGROUND Lignocellulose	113:137	BACKGROUND Lignocellulose	113:137	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	4	105	theme	important	798:806	arg1	aspects					808:814	important aspects	798:814	important aspects of lignocellulose degradation that will be central to optimizing commercial processes	798:900	Single-species approaches are, therefore, likely to miss important aspects of lignocellulose degradation that will be central to optimizing commercial processes.
29946357	9	106	from	Telotrochidium	1732:1745	arg1	ciliates					1712:1719	peritrich ciliates	1702:1719	peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance	1702:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	7	107	theme	gradual	1383:1389	arg1	decrease					1391:1398	a gradual decrease	1381:1398	a gradual decrease in complexity and diversity	1381:1426	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	7	108	dep	sequenced	1322:1330	arg1	eukaryotic					1346:1355	eukaryotic	1346:1355	eukaryotic	1346:1355	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	7	108	dep	sequenced	1322:1330	arg1	bacterial					1332:1340	bacterial	1332:1340	bacterial	1332:1340	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	8	109	theme	bacterial	1492:1500	arg1	species					1502:1508	bacterial species	1492:1508	bacterial species	1492:1508	Taxonomic affiliation of bacterial species showed dominance of Bacteroidetes and Proteobacteria and high relative abundance of genera Asticcacaulis, Leadbetterella and Truepera.
29946357	14	110	theme	carbohydrate-active	2697:2715	arg1	enzymes					2717:2723	the expected carbohydrate-active enzymes	2684:2723	the expected carbohydrate-active enzymes	2684:2723	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	9	111	attach	present	1820:1826	arg2	species					1802:1808	fungal species	1795:1808	fungal species that were present in low abundance	1795:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	9	111	attach	present	1820:1826	arg1	abundance					1835:1843	low abundance	1831:1843	low abundance	1831:1843	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	7	112	from	decrease	1391:1398	arg1	diversity					1418:1426	diversity	1418:1426	diversity	1418:1426	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	7	112	from	decrease	1391:1398	arg1	complexity					1403:1412	complexity	1403:1412	complexity	1403:1412	Phylogenetic composition of the community, based on sequenced bacterial and eukaryotic ribosomal genes, showed a gradual decrease in complexity and diversity over time due to microbial enrichment.
29946357	10	113	theme	culture	2069:2075	arg1	supernatant					2077:2087	the culture supernatant	2065:2087	the culture supernatant	2065:2087	A targeted metasecretome approach combined with metatranscriptomics analysis, identified 1127 proteins and showed the presence of numerous carbohydrate-active enzymes extracted from the biomass-bound fractions and from the culture supernatant.
29946357	1	114	theme	abundant	158:165	arg1	forms					167:171	the most abundant forms	149:171	the most abundant forms of fixed carbon in the biosphere	149:204	BACKGROUND Lignocellulose is one of the most abundant forms of fixed carbon in the biosphere.
29946357	14	115	theme	proteins	2771:2778	arg1	number					2753:2758	a large number	2745:2758	a large number	2745:2758	In addition to the expected carbohydrate-active enzymes, our studies reveal a large number of unknown proteins, some of which may play a crucial role in community-based lignocellulose degradation.
29946357	13	116	theme	improved	2598:2605	arg1	cocktails					2614:2622	improved enzyme cocktails	2598:2622	improved enzyme cocktails for the treatment of plant-based feedstocks	2598:2666	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	3	117	theme	"	709:709	arg1	metabolism					711:720	"community-level" metabolism	693:720	"community-level" metabolism of lignocellulose	693:738	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	3	118	theme	individual	524:533	arg1	species					545:551	individual microbial species	524:551	individual microbial species	524:551	While the enzymatic mechanisms of lignocellulose degradation have been characterized in detail in individual microbial species, the microbial communities that efficiently breakdown plant materials in nature are species rich and secrete a myriad of enzymes to perform "community-level" metabolism of lignocellulose.
29946357	13	119	theme	spectrometry-based	2394:2411	arg1	proteomics					2413:2422	mass spectrometry-based proteomics	2389:2422	mass spectrometry-based proteomics coupled with metatranscriptomics	2389:2455	CONCLUSIONS A combination of mass spectrometry-based proteomics coupled with metatranscriptomics has enabled the identification of a large number of lignocellulose degrading enzymes that can now be further explored for the development of improved enzyme cocktails for the treatment of plant-based feedstocks.
29946357	9	120	theme	liquid	1767:1772	arg1	cultures					1774:1781	the liquid cultures	1763:1781	the liquid cultures	1763:1781	The eukaryotic members of the community were enriched in peritrich ciliates from genus Telotrochidium that thrived in the liquid cultures compared to fungal species that were present in low abundance.
29946357	6	121	theme	lignocellulose	1178:1191	arg1	degradation					1193:1203	lignocellulose degradation	1178:1203	lignocellulose degradation	1178:1203	Samples taken at selected time points were subjected to multi-omics analysis with the aim of identifying new microbial mechanisms for lignocellulose degradation that could be applied in industrial pre-treatment of feedstocks.
30617158	7	0	theme	proteins	1161:1168	arg1	abundances					1106:1115	significantly reduced abundances	1084:1115	significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK	1084:1213	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	4	1	theme	independent	651:661	arg1	DIA-SWATH-MS					676:687	DIA-SWATH-MS	676:687	DIA-SWATH-MS	676:687	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	4	1	theme	independent	651:661	arg1	acquisition					663:673	independent acquisition	651:673	data independent acquisition (DIA-SWATH-MS)	646:688	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	7	2	theme	increased	1136:1144	arg1	ClpB					1181:1184	ClpB	1181:1184	ClpB	1181:1184	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	2	theme	increased	1136:1144	arg1	DnaK					1210:1213	DnaK	1210:1213	DnaK	1210:1213	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	2	theme	increased	1136:1144	arg1	GrpE					1201:1204	GrpE	1201:1204	GrpE	1201:1204	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	2	theme	increased	1136:1144	arg1	GroES					1194:1198	GroES	1194:1198	GroES	1194:1198	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	2	theme	increased	1136:1144	arg1	proteins					1161:1168	increased stress-related proteins	1136:1168	increased stress-related proteins	1136:1168	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	6	3	theme	pglB	843:846	arg1	ΔpglB					875:879	ΔpglB	875:879	ΔpglB	875:879	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	6	3	theme	pglB	843:846	arg1	oligosaccharyltransferase					848:872	the pglB oligosaccharyltransferase	839:872	the pglB oligosaccharyltransferase (ΔpglB)	839:880	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	6	4	theme	185	931:933	arg1	proteins					935:942	185 proteins	931:942	185 proteins	931:942	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	7	5	theme	targets	1124:1130	arg1	abundances					1106:1115	significantly reduced abundances	1084:1115	significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK	1084:1213	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	1	6	theme	prepared	206:213	arg1	poultry					215:221	poorly prepared poultry	199:221	poorly prepared poultry	199:221	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	6	7	theme	abundance	918:926	arg1	137					945:947	137	945:947	137	945:947	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	6	7	theme	abundance	918:926	arg1	abundance					918:926	abundance	918:926	abundance	918:926	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	11	8	theme	specific	2121:2128	arg1	reductase					2159:2167	Nap nitrate reductase	2147:2167	Nap nitrate reductase	2147:2167	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	11	8	theme	specific	2121:2128	arg1	activity					2137:2144	a specific enzyme activity	2119:2144	a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins	2119:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	0	9	link	N-linked	55:62	arg1	Glycosylation					64:76	N-linked Glycosylation	55:76	N-linked Glycosylation in Campylobacter jejuni	55:100	Proteomics Reveals Multiple Phenotypes Associated with N-linked Glycosylation in Campylobacter jejuni.
30617158	2	10	theme	nonsymptomatic	342:355	arg1	colonization					365:376	nonsymptomatic chicken colonization	342:376	nonsymptomatic chicken colonization	342:376	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	6	11	from	change	908:913	arg1	abundance					918:926	abundance	918:926	abundance	918:926	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	7	12	theme	reduced	1098:1104	arg1	abundances					1106:1115	significantly reduced abundances	1084:1115	significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK	1084:1213	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	6	13	theme	wild-type	981:989	arg1	levels					991:996	their wild-type levels	975:996	their wild-type levels	975:996	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	8	14	theme	negative	1438:1445	arg1	jejuni					1450:1455	pgl negative C. jejuni	1434:1455	pgl negative C. jejuni	1434:1455	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	4	15	from	effects	494:500	arg1	proteome					540:547	the C. jejuni proteome	526:547	the C. jejuni proteome	526:547	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	5	16	theme	genome	769:774	arg1	%					739:739	∼84%	736:739	∼84% of the C. jejuni NCTC 11168 genome	736:774	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	5	16	theme	genome	769:774	arg1	genome					769:774	the C. jejuni NCTC 11168 genome	744:774	the C. jejuni NCTC 11168 genome	744:774	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	2	17	theme	pgl	270:272	arg1	cluster					279:285	the pgl gene cluster	266:285	the pgl gene cluster	266:285	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	8	18	theme	reduced	1242:1248	arg1	survival					1250:1257	reduced survival	1242:1257	reduced survival	1242:1257	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	4	19	theme	pgl	505:507	arg1	deletion					514:521	pgl gene deletion	505:521	pgl gene deletion	505:521	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	11	20	theme	first	2071:2075	arg1	time					2077:2080	the first time	2067:2080	the first time	2067:2080	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	1	21	theme	gastrointestinal	135:150	arg1	pathogen					152:159	a major gastrointestinal pathogen	127:159	a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry	127:221	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	1	21	theme	gastrointestinal	135:150	arg1	jejuni					117:122	Campylobacter jejuni	103:122	Campylobacter jejuni	103:122	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	11	22	gly	N-glycosylation	2087:2101	arg1	enzyme					2130:2135	a specific enzyme activity	2119:2144	a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins	2119:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	9	23	theme	ΔpglB	1722:1726	arg1	chemotaxis					1728:1737	ΔpglB chemotaxis	1722:1737	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate)	1722:1804	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	12	24	theme	C.	2305:2306	arg1	physiology					2315:2324	C. jejuni physiology	2305:2324	C. jejuni physiology	2305:2324	These data indicate a multifactorial role for N-glycosylation in C. jejuni physiology.
30617158	8	25	theme	osmotic	1302:1308	arg1	shock					1324:1328	temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock	1269:1328	temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock	1269:1328	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	10	26	theme	acceptors	2020:2028	arg1	use					1992:1994	the use	1988:1994	the use of alternative electron acceptors	1988:2028	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	5	27	theme	C.	748:749	arg1	11168					763:767	the C. jejuni NCTC 11168	744:767	the C. jejuni NCTC 11168 genome	744:774	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	2	28	theme	>80	295:297	arg1	proteins					308:315	>80 membrane proteins	295:315	>80 membrane proteins	295:315	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	8	29	theme	proteome	1562:1569	arg1	DctA/DcuB					1657:1665	reduced DctA/DcuB	1649:1665	reduced DctA/DcuB (aspartate import and succinate export, respectively)	1649:1719	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	29	theme	proteome	1562:1569	arg1	changes					1571:1577	proteome changes	1562:1577	proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively)	1562:1719	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	29	theme	proteome	1562:1569	arg1	PutP/PutA					1598:1606	elevated PutP/PutA	1589:1606	elevated PutP/PutA (proline transport and utilization)	1589:1642	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	30	dep	jejuni	1388:1393	arg1	established					1417:1427	established	1417:1427	established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively)	1417:1719	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	6	31	theme	::	1037:1038	arg1	ΔpglB					1039:1043	Δaaz.batpglB::ΔpglB	1025:1043	Δaaz.batpglB::ΔpglB	1025:1043	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	6	31	theme	::	1037:1038	arg1	pglB					1019:1022	pglB	1019:1022	pglB (Δaaz.batpglB::ΔpglB)	1019:1044	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	11	32	theme	reduced	2194:2200	arg1	abundance					2202:2210	reduced abundance	2194:2210	reduced abundance of the NapAB glycoproteins	2194:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	4	33	theme	jejuni	533:538	arg1	proteome					540:547	the C. jejuni proteome	526:547	the C. jejuni proteome	526:547	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	12	34	from	role	2277:2280	arg1	physiology					2315:2324	C. jejuni physiology	2305:2324	C. jejuni physiology	2305:2324	These data indicate a multifactorial role for N-glycosylation in C. jejuni physiology.
30617158	8	35	theme	proline	1490:1496	arg1	uptake					1504:1509	proline (Pro) uptake	1490:1509	proline (Pro) uptake	1490:1509	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	10	36	theme	low	2036:2038	arg1	oxygen					2040:2045	low oxygen	2036:2045	low oxygen	2036:2045	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	11	37	theme	NapAB	2219:2223	arg1	glycoproteins					2225:2237	the NapAB glycoproteins	2215:2237	the NapAB glycoproteins	2215:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	4	38	theme	deletion	514:521	arg1	effects					494:500	the effects	490:500	the effects of pgl gene deletion on the C. jejuni proteome	490:547	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	8	39	dep	PutP/PutA	1598:1606	arg1	utilization					1631:1641	utilization	1631:1641	utilization	1631:1641	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	39	dep	PutP/PutA	1598:1606	arg1	transport					1617:1625	proline transport	1609:1625	proline transport	1609:1625	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	3	40	theme	biological	422:431	arg1	functions					433:441	the biological functions	418:441	the biological functions of N-glycosylation	418:460	Despite this, the biological functions of N-glycosylation remain unknown.
30617158	0	41	theme	Campylobacter	81:93	arg1	jejuni					95:100	Campylobacter jejuni	81:100	Campylobacter jejuni	81:100	Proteomics Reveals Multiple Phenotypes Associated with N-linked Glycosylation in Campylobacter jejuni.
30617158	8	42	dep	temperature	1269:1279	arg1	°C					1284:1285	4 °C and 46 °C	1282:1295	°C	1284:1285	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	42	dep	temperature	1269:1279	arg1	°C					1294:1295	4 °C and 46 °C	1282:1295	°C	1294:1295	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	11	43	theme	Nap	2147:2149	arg1	reductase					2159:2167	Nap nitrate reductase	2147:2167	Nap nitrate reductase	2147:2167	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	11	43	theme	Nap	2147:2149	arg1	activity					2137:2144	a specific enzyme activity	2119:2144	a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins	2119:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	8	44	theme	accumulated	1515:1525	arg1	succinate					1541:1549	accumulated intracellular succinate	1515:1549	accumulated intracellular succinate	1515:1549	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	0	45	theme	Multiple	19:26	arg1	Phenotypes					28:37	Multiple Phenotypes	19:37	Multiple Phenotypes Associated with N-linked Glycosylation in Campylobacter jejuni	19:100	Proteomics Reveals Multiple Phenotypes Associated with N-linked Glycosylation in Campylobacter jejuni.
30617158	8	46	theme	C.	1385:1386	arg1	jejuni					1388:1393	wild-type C. jejuni	1375:1393	wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively)	1375:1719	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	6	47	theme	significant	896:906	arg1	change					908:913	a significant change	894:913	a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB)	894:1044	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	10	48	theme	alternative	1999:2009	arg1	acceptors					2020:2028	alternative electron acceptors	1999:2028	alternative electron acceptors	1999:2028	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	4	49	theme	liquid	567:572	arg1	LC-MS/MS					615:622	LC-MS/MS	615:622	LC-MS/MS	615:622	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	4	49	theme	liquid	567:572	arg1	spectrometry					601:612	label-based liquid chromatography/tandem mass spectrometry	555:612	label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS)	555:623	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	8	50	theme	Targeted	1395:1402	arg1	metabolomics					1404:1415	Targeted metabolomics	1395:1415	Targeted metabolomics	1395:1415	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	2	51	theme	human	387:391	arg1	virulence					393:401	full human virulence	382:401	full human virulence	382:401	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	0	52	theme	N-linked	55:62	arg1	Glycosylation					64:76	N-linked Glycosylation	55:76	N-linked Glycosylation in Campylobacter jejuni	55:100	Proteomics Reveals Multiple Phenotypes Associated with N-linked Glycosylation in Campylobacter jejuni.
30617158	4	53	theme	mass	596:599	arg1	LC-MS/MS					615:622	LC-MS/MS	615:622	LC-MS/MS	615:622	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	4	53	theme	mass	596:599	arg1	spectrometry					601:612	label-based liquid chromatography/tandem mass spectrometry	555:612	label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS)	555:623	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	8	54	theme	elevated	1589:1596	arg1	PutP/PutA					1598:1606	elevated PutP/PutA	1589:1606	elevated PutP/PutA (proline transport and utilization)	1589:1642	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	2	55	theme	N-linked	224:231	arg1	glycosylation					241:253	N-linked protein glycosylation	224:253	N-linked protein glycosylation encoded by the pgl gene cluster	224:285	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	8	56	theme	pgl	1434:1436	arg1	jejuni					1450:1455	pgl negative C. jejuni	1434:1455	pgl negative C. jejuni	1434:1455	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	57	theme	reduced	1649:1655	arg1	DctA/DcuB					1657:1665	reduced DctA/DcuB	1649:1665	reduced DctA/DcuB (aspartate import and succinate export, respectively)	1649:1719	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	9	58	theme	transducer-like	1859:1873	arg1	proteins					1881:1888	transducer-like (Tlp) proteins	1859:1888	transducer-like (Tlp) proteins	1859:1888	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	10	59	theme	Glycosylation	1891:1903	arg1	jejuni					1917:1922	Glycosylation negative C. jejuni	1891:1922	Glycosylation negative C. jejuni	1891:1922	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	7	60	theme	stress-related	1146:1159	arg1	ClpB					1181:1184	ClpB	1181:1184	ClpB	1181:1184	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	60	theme	stress-related	1146:1159	arg1	DnaK					1210:1213	DnaK	1210:1213	DnaK	1210:1213	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	60	theme	stress-related	1146:1159	arg1	GrpE					1201:1204	GrpE	1201:1204	GrpE	1201:1204	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	60	theme	stress-related	1146:1159	arg1	GroES					1194:1198	GroES	1194:1198	GroES	1194:1198	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	60	theme	stress-related	1146:1159	arg1	proteins					1161:1168	increased stress-related proteins	1136:1168	increased stress-related proteins	1136:1168	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	9	61	theme	Tlp	1876:1878	arg1	proteins					1881:1888	transducer-like (Tlp) proteins	1859:1888	transducer-like (Tlp) proteins	1859:1888	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	6	62	theme	oligosaccharyltransferase	848:872	arg1	Deletion					827:834	Deletion	827:834	Deletion of the pglB oligosaccharyltransferase (ΔpglB)	827:880	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	6	63	theme	proteins	935:942	arg1	abundance					918:926	abundance	918:926	abundance	918:926	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	11	64	gly	glycoproteins	2225:2237	arg1	glycoproteins					2225:2237	the NapAB glycoproteins	2215:2237	the NapAB glycoproteins	2215:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	9	65	theme	proteins	1881:1888	arg1	abundance					1846:1854	altered abundance	1838:1854	altered abundance of transducer-like (Tlp) proteins	1838:1888	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	7	66	theme	pgl	1120:1122	arg1	ClpB					1181:1184	ClpB	1181:1184	ClpB	1181:1184	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	66	theme	pgl	1120:1122	arg1	DnaK					1210:1213	DnaK	1210:1213	DnaK	1210:1213	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	66	theme	pgl	1120:1122	arg1	GrpE					1201:1204	GrpE	1201:1204	GrpE	1201:1204	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	66	theme	pgl	1120:1122	arg1	targets					1124:1130	pgl targets	1120:1130	pgl targets	1120:1130	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	7	66	theme	pgl	1120:1122	arg1	GroES					1194:1198	GroES	1194:1198	GroES	1194:1198	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	8	67	theme	succinate	1689:1697	arg1	export					1699:1704	succinate export	1689:1704	succinate export	1689:1704	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	10	68	theme	C.	1914:1915	arg1	jejuni					1917:1922	Glycosylation negative C. jejuni	1891:1922	Glycosylation negative C. jejuni	1891:1922	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	2	69	theme	chicken	357:363	arg1	colonization					365:376	nonsymptomatic chicken colonization	342:376	nonsymptomatic chicken colonization	342:376	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	1	70	theme	poultry	215:221	arg1	consumption					184:194	consumption	184:194	consumption of poorly prepared poultry	184:221	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	11	71	theme	enzyme	2130:2135	arg1	reductase					2159:2167	Nap nitrate reductase	2147:2167	Nap nitrate reductase	2147:2167	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	11	71	theme	enzyme	2130:2135	arg1	activity					2137:2144	a specific enzyme activity	2119:2144	a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins	2119:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	8	72	theme	temperature	1269:1279	arg1	shock					1324:1328	temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock	1269:1328	temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock	1269:1328	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	10	73	theme	respiration-associated	1945:1966	arg1	proteins					1968:1975	all respiration-associated proteins	1941:1975	all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen	1941:2045	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	5	74	theme	jejuni	751:756	arg1	11168					763:767	the C. jejuni NCTC 11168	744:767	the C. jejuni NCTC 11168 genome	744:774	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	8	75	theme	C.	1447:1448	arg1	jejuni					1450:1455	pgl negative C. jejuni	1434:1455	pgl negative C. jejuni	1434:1455	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	5	76	theme	11168	763:767	arg1	genome					769:774	the C. jejuni NCTC 11168 genome	744:774	the C. jejuni NCTC 11168 genome	744:774	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	4	77	dep	data	646:649	arg1	DIA-SWATH-MS					676:687	DIA-SWATH-MS	676:687	DIA-SWATH-MS	676:687	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	4	77	dep	data	646:649	arg1	acquisition					663:673	independent acquisition	651:673	data independent acquisition (DIA-SWATH-MS)	646:688	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	2	78	theme	gene	274:277	arg1	cluster					279:285	the pgl gene cluster	266:285	the pgl gene cluster	266:285	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	8	79	theme	pglB	1216:1219	arg1	mutants					1221:1227	pglB mutants	1216:1227	pglB mutants	1216:1227	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	4	80	theme	gene	509:512	arg1	deletion					514:521	pgl gene deletion	505:521	pgl gene deletion	505:521	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	7	81	theme	pglB	1059:1062	arg1	Deletion					1047:1054	Deletion	1047:1054	Deletion of pglB	1047:1062	Deletion of pglB was associated with significantly reduced abundances of pgl targets and increased stress-related proteins, including ClpB, GroEL, GroES, GrpE and DnaK.
30617158	1	82	theme	major	129:133	arg1	pathogen					152:159	a major gastrointestinal pathogen	127:159	a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry	127:221	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	1	82	theme	major	129:133	arg1	jejuni					117:122	Campylobacter jejuni	103:122	Campylobacter jejuni	103:122	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	9	83	dep	substrates	1747:1756	arg1	α-ketoglutarate					1789:1803	α-ketoglutarate	1789:1803	α-ketoglutarate	1789:1803	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	9	83	dep	substrates	1747:1756	arg1	substrates					1747:1756	some substrates	1742:1756	some substrates (Asp, glutamate, succinate and α-ketoglutarate)	1742:1804	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	9	83	dep	substrates	1747:1756	arg1	succinate					1775:1783	succinate	1775:1783	succinate	1775:1783	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	9	83	dep	substrates	1747:1756	arg1	glutamate					1764:1772	glutamate	1764:1772	glutamate	1764:1772	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	9	83	dep	substrates	1747:1756	arg1	Asp					1759:1761	Asp	1759:1761	Asp	1759:1761	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	12	84	theme	jejuni	2308:2313	arg1	physiology					2315:2324	C. jejuni physiology	2305:2324	C. jejuni physiology	2305:2324	These data indicate a multifactorial role for N-glycosylation in C. jejuni physiology.
30617158	2	85	gly	glycosylation	241:253	arg1	chicken					357:363	nonsymptomatic chicken colonization	342:376	nonsymptomatic chicken colonization	342:376	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	2	86	theme	membrane	299:306	arg1	proteins					308:315	>80 membrane proteins	295:315	>80 membrane proteins	295:315	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	8	87	dep	DctA/DcuB	1657:1665	arg1	import					1678:1683	aspartate import	1668:1683	aspartate import	1668:1683	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	87	dep	DctA/DcuB	1657:1665	arg1	export					1699:1704	succinate export	1689:1704	succinate export	1689:1704	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	10	88	theme	electron	2011:2018	arg1	acceptors					2020:2028	alternative electron acceptors	1999:2028	alternative electron acceptors	1999:2028	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	5	89	theme	these	789:793	arg1	1080					781:784	1080	781:784	1080	781:784	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	5	89	theme	these	789:793	arg1	these					789:793	these	789:793	these	789:793	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	6	90	theme	Δaaz.batpglB	1025:1036	arg1	ΔpglB					1039:1043	Δaaz.batpglB::ΔpglB	1025:1043	Δaaz.batpglB::ΔpglB	1025:1043	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	6	90	theme	Δaaz.batpglB	1025:1036	arg1	pglB					1019:1022	pglB	1019:1022	pglB (Δaaz.batpglB::ΔpglB)	1019:1044	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	5	91	theme	NCTC	758:761	arg1	11168					763:767	the C. jejuni NCTC 11168	744:767	the C. jejuni NCTC 11168 genome	744:774	We quantified 1359 proteins corresponding to ∼84% of the C. jejuni NCTC 11168 genome, and 1080 of these were validated by DIA-SWATH-MS.
30617158	4	92	theme	label-based	555:565	arg1	LC-MS/MS					615:622	LC-MS/MS	615:622	LC-MS/MS	615:622	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	4	92	theme	label-based	555:565	arg1	spectrometry					601:612	label-based liquid chromatography/tandem mass spectrometry	555:612	label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS)	555:623	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	8	93	theme	mm	1315:1316	arg1	osmotic					1302:1308	osmotic	1302:1308	osmotic (150 mm NaCl)	1302:1322	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	93	theme	mm	1315:1316	arg1	NaCl					1318:1321	150 mm NaCl	1311:1321	150 mm NaCl	1311:1321	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	6	94	theme	pglB	1019:1022	arg1	reintroduction					1001:1014	reintroduction	1001:1014	reintroduction of pglB (Δaaz.batpglB::ΔpglB)	1001:1044	Deletion of the pglB oligosaccharyltransferase (ΔpglB) resulted in a significant change in abundance of 185 proteins, 137 of which were restored to their wild-type levels by reintroduction of pglB (Δaaz.batpglB::ΔpglB).
30617158	0	95	from	Glycosylation	64:76	arg1	jejuni					95:100	Campylobacter jejuni	81:100	Campylobacter jejuni	81:100	Proteomics Reveals Multiple Phenotypes Associated with N-linked Glycosylation in Campylobacter jejuni.
30617158	11	96	theme	glycoproteins	2225:2237	arg1	abundance					2202:2210	reduced abundance	2194:2210	reduced abundance of the NapAB glycoproteins	2194:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	4	97	theme	C.	530:531	arg1	proteome					540:547	the C. jejuni proteome	526:547	the C. jejuni proteome	526:547	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	1	98	theme	Campylobacter	103:115	arg1	pathogen					152:159	a major gastrointestinal pathogen	127:159	a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry	127:221	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	1	98	theme	Campylobacter	103:115	arg1	jejuni					117:122	Campylobacter jejuni	103:122	Campylobacter jejuni	103:122	Campylobacter jejuni is a major gastrointestinal pathogen generally acquired via consumption of poorly prepared poultry.
30617158	8	99	theme	Pro	1499:1501	arg1	uptake					1504:1509	proline (Pro) uptake	1490:1509	proline (Pro) uptake	1490:1509	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	100	theme	intracellular	1527:1539	arg1	succinate					1541:1549	accumulated intracellular succinate	1515:1549	accumulated intracellular succinate	1515:1549	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	8	101	theme	biofilm	1342:1348	arg1	phenotypes					1350:1359	biofilm phenotypes	1342:1359	biofilm phenotypes	1342:1359	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	11	102	theme	nitrate	2151:2157	arg1	reductase					2159:2167	Nap nitrate reductase	2147:2167	Nap nitrate reductase	2147:2167	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	11	102	theme	nitrate	2151:2157	arg1	activity					2137:2144	a specific enzyme activity	2119:2144	a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins	2119:2237	We demonstrate for the first time that N-glycosylation is required for a specific enzyme activity (Nap nitrate reductase) that is associated with reduced abundance of the NapAB glycoproteins.
30617158	8	103	theme	related	1551:1557	arg1	uptake					1504:1509	proline (Pro) uptake	1490:1509	proline (Pro) uptake	1490:1509	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	2	104	link	N-linked	224:231	arg1	glycosylation					241:253	N-linked protein glycosylation	224:253	N-linked protein glycosylation encoded by the pgl gene cluster	224:285	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	4	105	theme	chromatography/tandem	574:594	arg1	LC-MS/MS					615:622	LC-MS/MS	615:622	LC-MS/MS	615:622	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	4	105	theme	chromatography/tandem	574:594	arg1	spectrometry					601:612	label-based liquid chromatography/tandem mass spectrometry	555:612	label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS)	555:623	We examined the effects of pgl gene deletion on the C. jejuni proteome using label-based liquid chromatography/tandem mass spectrometry (LC-MS/MS) and validation using data independent acquisition (DIA-SWATH-MS).
30617158	8	106	theme	wild-type	1375:1383	arg1	jejuni					1388:1393	wild-type C. jejuni	1375:1393	wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively)	1375:1719	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	12	107	theme	multifactorial	2262:2275	arg1	role					2277:2280	a multifactorial role	2260:2280	a multifactorial role for N-glycosylation in C. jejuni physiology	2260:2324	These data indicate a multifactorial role for N-glycosylation in C. jejuni physiology.
30617158	3	108	theme	N-glycosylation	446:460	arg1	functions					433:441	the biological functions	418:441	the biological functions of N-glycosylation	418:460	Despite this, the biological functions of N-glycosylation remain unknown.
30617158	2	109	theme	full	382:385	arg1	virulence					393:401	full human virulence	382:401	full human virulence	382:401	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	9	110	theme	altered	1838:1844	arg1	abundance					1846:1854	altered abundance	1838:1854	altered abundance of transducer-like (Tlp) proteins	1838:1888	ΔpglB chemotaxis to some substrates (Asp, glutamate, succinate and α-ketoglutarate) was reduced and associated with altered abundance of transducer-like (Tlp) proteins.
30617158	2	111	theme	protein	233:239	arg1	glycosylation					241:253	N-linked protein glycosylation	224:253	N-linked protein glycosylation encoded by the pgl gene cluster	224:285	N-linked protein glycosylation encoded by the pgl gene cluster targets >80 membrane proteins and is required for both nonsymptomatic chicken colonization and full human virulence.
30617158	8	112	theme	proline	1609:1615	arg1	transport					1617:1625	proline transport	1609:1625	proline transport	1609:1625	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30617158	10	113	theme	negative	1905:1912	arg1	jejuni					1917:1922	Glycosylation negative C. jejuni	1891:1922	Glycosylation negative C. jejuni	1891:1922	Glycosylation negative C. jejuni were depleted of all respiration-associated proteins that allow the use of alternative electron acceptors under low oxygen.
30617158	8	114	theme	aspartate	1668:1676	arg1	import					1678:1683	aspartate import	1668:1683	aspartate import	1668:1683	pglB mutants demonstrated reduced survival following temperature (4 °C and 46 °C) and osmotic (150 mm NaCl) shock and altered biofilm phenotypes compared with wild-type C. jejuni Targeted metabolomics established that pgl negative C. jejuni switched from aspartate (Asp) to proline (Pro) uptake and accumulated intracellular succinate related to proteome changes including elevated PutP/PutA (proline transport and utilization), and reduced DctA/DcuB (aspartate import and succinate export, respectively).
30566828	6	0	link	N-linked	693:700	arg1	glycosylation					702:714	N-linked glycosylation	693:714	N-linked glycosylation	693:714	When N-linked glycosylation was inhibited by tunicamycin or abolished by the N39Q, N39A, or T41A mutation, CTRP12 cleavage was enhanced.
30566828	1	1	theme	secreted	156:163	arg1	protein					131:137	C1q/TNF-related protein 12	115:140	C1q/TNF-related protein 12 (CTRP12)	115:149	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	1	1	theme	secreted	156:163	arg1	regulator					165:173	a secreted regulator	154:173	a secreted regulator of glucose and lipid metabolism	154:205	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	14	2	theme	biosynthesis	1754:1765	arg1	pathway					1767:1773	the hexosamine biosynthesis pathway	1739:1773	the hexosamine biosynthesis pathway	1739:1773	Lastly, we show that increasing the flux through the hexosamine biosynthesis pathway by exogenous glucosamine, known to disrupt protein glycosylation, also promoted CTRP12 cleavage.
30566828	9	3	theme	CTRP12	1183:1188	arg1	cleavage					1190:1197	CTRP12 cleavage	1183:1197	CTRP12 cleavage	1183:1197	Replacing the nonglycosylated Asn-297 with glutamine or alanine also increased CTRP12 cleavage.
30566828	10	4	theme	maximum	1270:1276	arg1	cleavage					1278:1285	maximum cleavage	1270:1285	maximum cleavage	1270:1285	Both Asn-39 and Asn-297 contributed independently to CTRP12 cleavage: maximum cleavage was observed in the double mutant.
30566828	5	5	theme	direct	647:652	arg1	evidence					654:661	direct evidence	647:661	direct evidence of Asn-39 glycosylation	647:685	Mass spectrometry analysis provided direct evidence of Asn-39 glycosylation.
30566828	13	6	theme	protein	1637:1643	arg1	stability					1645:1653	reduced protein stability	1629:1653	reduced protein stability for N39Q, T41A, and N297Q mutants	1629:1687	Cycloheximide chase analyses indicated reduced protein stability for N39Q, T41A, and N297Q mutants.
30566828	8	7	theme	hybrid	985:990	arg1	N-glycans					1009:1017	hybrid and complex-type N-glycans	985:1017	N-glycans	1009:1017	In N-acetylglucosaminyltransferase I (GnTI)-deficient cells that could not form hybrid and complex-type N-glycans in the Golgi, CTRP12 cleavage was enhanced, and re-expressing GnTI reduced cleavage.
30566828	10	8	theme	double	1307:1312	arg1	mutant					1314:1319	the double mutant	1303:1319	the double mutant	1303:1319	Both Asn-39 and Asn-297 contributed independently to CTRP12 cleavage: maximum cleavage was observed in the double mutant.
30566828	4	9	theme	CTRP12	568:573	arg1	cleavage					575:582	CTRP12 cleavage	568:582	CTRP12 cleavage	568:582	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	3	10	theme	different	355:363	arg1	pathways					375:382	different signaling pathways	355:382	different signaling pathways	355:382	These isoforms preferentially activate different signaling pathways, and their ratio in plasma is altered in obesity and diabetes.
30566828	12	11	theme	nonglycosylated	1441:1455	arg1	Asn-287					1457:1463	the nonglycosylated Asn-287	1437:1463	the nonglycosylated Asn-287	1437:1463	Replacing the nonglycosylated Asn-287 with glutamine or alanine resulted in protein misfolding and aggregation, leading to retention in the endoplasmic reticulum.
30566828	6	12	theme	T41A	780:783	arg1	mutation					785:792	the N39Q, N39A, or T41A mutation	761:792	the N39Q, N39A, or T41A mutation	761:792	When N-linked glycosylation was inhibited by tunicamycin or abolished by the N39Q, N39A, or T41A mutation, CTRP12 cleavage was enhanced.
30566828	2	13	theme	cleaved	265:271	arg1	isoform					273:279	a cleaved isoform	263:279	a cleaved isoform generated by furin/PCSK3 cleavage	263:313	It circulates in plasma as a full-length protein or as a cleaved isoform generated by furin/PCSK3 cleavage.
30566828	3	14	theme	signaling	365:373	arg1	pathways					375:382	different signaling pathways	355:382	different signaling pathways	355:382	These isoforms preferentially activate different signaling pathways, and their ratio in plasma is altered in obesity and diabetes.
30566828	4	15	theme	asparagine	482:491	arg1	Asn-287					511:517	Asn-287	511:517	Asn-287	511:517	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	15	theme	asparagine	482:491	arg1	Asn-297					524:530	Asn-297	524:530	Asn-297	524:530	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	15	theme	asparagine	482:491	arg1	Asn-39					503:508	Asn-39	503:508	Asn-39	503:508	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	15	theme	asparagine	482:491	arg1	residues					493:500	three conserved asparagine residues	466:500	three conserved asparagine residues (Asn-39, Asn-287, and Asn-297)	466:531	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	14	16	theme	exogenous	1778:1786	arg1	glucosamine					1788:1798	exogenous glucosamine	1778:1798	exogenous glucosamine	1778:1798	Lastly, we show that increasing the flux through the hexosamine biosynthesis pathway by exogenous glucosamine, known to disrupt protein glycosylation, also promoted CTRP12 cleavage.
30566828	8	17	theme	complex-type	996:1007	arg1	N-glycans					1009:1017	hybrid and complex-type N-glycans	985:1017	N-glycans	1009:1017	In N-acetylglucosaminyltransferase I (GnTI)-deficient cells that could not form hybrid and complex-type N-glycans in the Golgi, CTRP12 cleavage was enhanced, and re-expressing GnTI reduced cleavage.
30566828	6	18	theme	N-linked	693:700	arg1	glycosylation					702:714	N-linked glycosylation	693:714	N-linked glycosylation	693:714	When N-linked glycosylation was inhibited by tunicamycin or abolished by the N39Q, N39A, or T41A mutation, CTRP12 cleavage was enhanced.
30566828	1	19	theme	glucose	178:184	arg1	protein					131:137	C1q/TNF-related protein 12	115:140	C1q/TNF-related protein 12 (CTRP12)	115:149	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	1	19	theme	glucose	178:184	arg1	regulator					165:173	a secreted regulator	154:173	a secreted regulator of glucose and lipid metabolism	154:205	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	0	20	theme	Glycosylation-Dependent	9:31	arg1	Mechanisms					50:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms	0:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms	0:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms Regulating CTRP12 Cleavage, Secretion, and Stability.
30566828	4	21	theme	conserved	472:480	arg1	Asn-287					511:517	Asn-287	511:517	Asn-287	511:517	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	21	theme	conserved	472:480	arg1	Asn-297					524:530	Asn-297	524:530	Asn-297	524:530	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	21	theme	conserved	472:480	arg1	Asn-39					503:508	Asn-39	503:508	Asn-39	503:508	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	21	theme	conserved	472:480	arg1	residues					493:500	three conserved asparagine residues	466:500	three conserved asparagine residues (Asn-39, Asn-287, and Asn-297)	466:531	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	5	22	theme	Mass	611:614	arg1	analysis					629:636	Mass spectrometry analysis	611:636	Mass spectrometry analysis	611:636	Mass spectrometry analysis provided direct evidence of Asn-39 glycosylation.
30566828	0	23	theme	N-Linked	0:7	arg1	Mechanisms					50:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms	0:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms	0:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms Regulating CTRP12 Cleavage, Secretion, and Stability.
30566828	5	24	theme	spectrometry	616:627	arg1	analysis					629:636	Mass spectrometry analysis	611:636	Mass spectrometry analysis	611:636	Mass spectrometry analysis provided direct evidence of Asn-39 glycosylation.
30566828	6	25	theme	N39A	771:774	arg1	mutation					785:792	the N39Q, N39A, or T41A mutation	761:792	the N39Q, N39A, or T41A mutation	761:792	When N-linked glycosylation was inhibited by tunicamycin or abolished by the N39Q, N39A, or T41A mutation, CTRP12 cleavage was enhanced.
30566828	13	26	theme	reduced	1629:1635	arg1	stability					1645:1653	reduced protein stability	1629:1653	reduced protein stability for N39Q, T41A, and N297Q mutants	1629:1687	Cycloheximide chase analyses indicated reduced protein stability for N39Q, T41A, and N297Q mutants.
30566828	1	27	theme	lipid	190:194	arg1	metabolism					196:205	lipid metabolism	190:205	lipid metabolism	190:205	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	0	28	theme	-Independent	37:48	arg1	Mechanisms					50:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms	0:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms	0:59	N-Linked Glycosylation-Dependent and -Independent Mechanisms Regulating CTRP12 Cleavage, Secretion, and Stability.
30566828	14	29	theme	CTRP12	1855:1860	arg1	cleavage					1862:1869	CTRP12 cleavage	1855:1869	CTRP12 cleavage	1855:1869	Lastly, we show that increasing the flux through the hexosamine biosynthesis pathway by exogenous glucosamine, known to disrupt protein glycosylation, also promoted CTRP12 cleavage.
30566828	8	30	theme	re-expressing	1067:1079	arg1	GnTI					1081:1084	re-expressing GnTI	1067:1084	re-expressing GnTI	1067:1084	In N-acetylglucosaminyltransferase I (GnTI)-deficient cells that could not form hybrid and complex-type N-glycans in the Golgi, CTRP12 cleavage was enhanced, and re-expressing GnTI reduced cleavage.
30566828	2	31	theme	furin/PCSK3	294:304	arg1	cleavage					306:313	furin/PCSK3 cleavage	294:313	furin/PCSK3 cleavage	294:313	It circulates in plasma as a full-length protein or as a cleaved isoform generated by furin/PCSK3 cleavage.
30566828	1	32	theme	metabolism	196:205	arg1	protein					131:137	C1q/TNF-related protein 12	115:140	C1q/TNF-related protein 12 (CTRP12)	115:149	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	1	32	theme	metabolism	196:205	arg1	regulator					165:173	a secreted regulator	154:173	a secreted regulator of glucose and lipid metabolism	154:205	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	11	33	theme	CTRP12	1335:1340	arg1	cleavage					1342:1349	CTRP12 cleavage	1335:1349	CTRP12 cleavage	1335:1349	In addition, CTRP12 cleavage was abolished in furin-deficient cells and restored by furin re-expression.
30566828	14	34	theme	hexosamine	1743:1752	arg1	pathway					1767:1773	the hexosamine biosynthesis pathway	1739:1773	the hexosamine biosynthesis pathway	1739:1773	Lastly, we show that increasing the flux through the hexosamine biosynthesis pathway by exogenous glucosamine, known to disrupt protein glycosylation, also promoted CTRP12 cleavage.
30566828	15	35	theme	protein	1998:2004	arg1	stability					2006:2014	protein stability	1998:2014	protein stability	1998:2014	Combined, these data highlight glycosylation-dependent and -independent mechanisms regulating CTRP12 cleavage, secretion, and protein stability.
30566828	13	36	theme	N297Q	1675:1679	arg1	mutants					1681:1687	N297Q mutants	1675:1687	N297Q mutants	1675:1687	Cycloheximide chase analyses indicated reduced protein stability for N39Q, T41A, and N297Q mutants.
30566828	11	37	theme	furin-deficient	1368:1382	arg1	cells					1384:1388	furin-deficient cells	1368:1388	furin-deficient cells	1368:1388	In addition, CTRP12 cleavage was abolished in furin-deficient cells and restored by furin re-expression.
30566828	4	38	theme	important	538:546	arg1	roles					548:552	important roles	538:552	important roles	538:552	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	15	39	theme	CTRP12	1966:1971	arg1	cleavage					1973:1980	CTRP12 cleavage	1966:1980	CTRP12 cleavage	1966:1980	Combined, these data highlight glycosylation-dependent and -independent mechanisms regulating CTRP12 cleavage, secretion, and protein stability.
30566828	9	40	theme	nonglycosylated	1118:1132	arg1	Asn-297					1134:1140	the nonglycosylated Asn-297	1114:1140	the nonglycosylated Asn-297	1114:1140	Replacing the nonglycosylated Asn-297 with glutamine or alanine also increased CTRP12 cleavage.
30566828	13	41	theme	Cycloheximide	1590:1602	arg1	analyses					1610:1617	Cycloheximide chase analyses	1590:1617	Cycloheximide chase analyses	1590:1617	Cycloheximide chase analyses indicated reduced protein stability for N39Q, T41A, and N297Q mutants.
30566828	6	42	theme	N39Q	765:768	arg1	mutation					785:792	the N39Q, N39A, or T41A mutation	761:792	the N39Q, N39A, or T41A mutation	761:792	When N-linked glycosylation was inhibited by tunicamycin or abolished by the N39Q, N39A, or T41A mutation, CTRP12 cleavage was enhanced.
30566828	15	43	theme	-independent	1931:1942	arg1	mechanisms					1944:1953	glycosylation-dependent and -independent mechanisms	1903:1953	glycosylation-dependent and -independent mechanisms regulating CTRP12 cleavage, secretion, and protein stability	1903:2014	Combined, these data highlight glycosylation-dependent and -independent mechanisms regulating CTRP12 cleavage, secretion, and protein stability.
30566828	11	44	theme	furin	1406:1410	arg1	re-expression					1412:1424	furin re-expression	1406:1424	furin re-expression	1406:1424	In addition, CTRP12 cleavage was abolished in furin-deficient cells and restored by furin re-expression.
30566828	13	45	theme	chase	1604:1608	arg1	analyses					1610:1617	Cycloheximide chase analyses	1590:1617	Cycloheximide chase analyses	1590:1617	Cycloheximide chase analyses indicated reduced protein stability for N39Q, T41A, and N297Q mutants.
30566828	3	46	from	ratio	395:399	arg1	plasma					404:409	plasma	404:409	plasma	404:409	These isoforms preferentially activate different signaling pathways, and their ratio in plasma is altered in obesity and diabetes.
30566828	0	47	theme	CTRP12	72:77	arg1	Cleavage					79:86	CTRP12 Cleavage	72:86	CTRP12 Cleavage	72:86	N-Linked Glycosylation-Dependent and -Independent Mechanisms Regulating CTRP12 Cleavage, Secretion, and Stability.
30566828	14	48	theme	protein	1818:1824	arg1	glycosylation					1826:1838	protein glycosylation	1818:1838	protein glycosylation	1818:1838	Lastly, we show that increasing the flux through the hexosamine biosynthesis pathway by exogenous glucosamine, known to disrupt protein glycosylation, also promoted CTRP12 cleavage.
30566828	5	49	theme	Asn-39	666:671	arg1	glycosylation					673:685	Asn-39 glycosylation	666:685	Asn-39 glycosylation	666:685	Mass spectrometry analysis provided direct evidence of Asn-39 glycosylation.
30566828	8	50	theme	CTRP12	1033:1038	arg1	cleavage					1040:1047	CTRP12 cleavage	1033:1047	CTRP12 cleavage	1033:1047	In N-acetylglucosaminyltransferase I (GnTI)-deficient cells that could not form hybrid and complex-type N-glycans in the Golgi, CTRP12 cleavage was enhanced, and re-expressing GnTI reduced cleavage.
30566828	10	51	located	observed	1291:1298	arg2	cleavage					1278:1285	maximum cleavage	1270:1285	maximum cleavage	1270:1285	Both Asn-39 and Asn-297 contributed independently to CTRP12 cleavage: maximum cleavage was observed in the double mutant.
30566828	10	51	located	observed	1291:1298	arg1	mutant					1314:1319	the double mutant	1303:1319	the double mutant	1303:1319	Both Asn-39 and Asn-297 contributed independently to CTRP12 cleavage: maximum cleavage was observed in the double mutant.
30566828	4	52	dep	residues	493:500	arg1	Asn-287					511:517	Asn-287	511:517	Asn-287	511:517	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	52	dep	residues	493:500	arg1	Asn-297					524:530	Asn-297	524:530	Asn-297	524:530	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	52	dep	residues	493:500	arg1	Asn-39					503:508	Asn-39	503:508	Asn-39	503:508	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	4	52	dep	residues	493:500	arg1	residues					493:500	three conserved asparagine residues	466:500	three conserved asparagine residues (Asn-39, Asn-287, and Asn-297)	466:531	Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability.
30566828	5	53	theme	glycosylation	673:685	arg1	evidence					654:661	direct evidence	647:661	direct evidence of Asn-39 glycosylation	647:685	Mass spectrometry analysis provided direct evidence of Asn-39 glycosylation.
30566828	1	54	theme	C1q/TNF-related	115:129	arg1	CTRP12					143:148	CTRP12	143:148	CTRP12	143:148	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	1	54	theme	C1q/TNF-related	115:129	arg1	regulator					165:173	a secreted regulator	154:173	a secreted regulator of glucose and lipid metabolism	154:205	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	1	54	theme	C1q/TNF-related	115:129	arg1	protein					131:137	C1q/TNF-related protein 12	115:140	C1q/TNF-related protein 12 (CTRP12)	115:149	C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism.
30566828	7	55	from	N-glycans	838:846	arg1	CTRP12					851:856	CTRP12	851:856	CTRP12	851:856	Complex-type N-glycans on CTRP12 blocked cleavage by the Golgi-localized furin.
30566828	8	56	theme	-deficient	948:957	arg1	cells					959:963	N-acetylglucosaminyltransferase I (GnTI)-deficient cells	908:963	N-acetylglucosaminyltransferase I (GnTI)-deficient cells that could not form hybrid and complex-type N-glycans in the Golgi	908:1030	In N-acetylglucosaminyltransferase I (GnTI)-deficient cells that could not form hybrid and complex-type N-glycans in the Golgi, CTRP12 cleavage was enhanced, and re-expressing GnTI reduced cleavage.
30566828	7	57	theme	Golgi-localized	882:896	arg1	furin					898:902	the Golgi-localized furin	878:902	the Golgi-localized furin	878:902	Complex-type N-glycans on CTRP12 blocked cleavage by the Golgi-localized furin.
30566828	7	58	theme	Complex-type	825:836	arg1	N-glycans					838:846	Complex-type N-glycans	825:846	Complex-type N-glycans on CTRP12	825:856	Complex-type N-glycans on CTRP12 blocked cleavage by the Golgi-localized furin.
30566828	15	59	theme	glycosylation-dependent	1903:1925	arg1	mechanisms					1944:1953	glycosylation-dependent and -independent mechanisms	1903:1953	glycosylation-dependent and -independent mechanisms regulating CTRP12 cleavage, secretion, and protein stability	1903:2014	Combined, these data highlight glycosylation-dependent and -independent mechanisms regulating CTRP12 cleavage, secretion, and protein stability.
30566828	12	60	theme	endoplasmic	1567:1577	arg1	reticulum					1579:1587	the endoplasmic reticulum	1563:1587	the endoplasmic reticulum	1563:1587	Replacing the nonglycosylated Asn-287 with glutamine or alanine resulted in protein misfolding and aggregation, leading to retention in the endoplasmic reticulum.
30566828	12	61	gly	nonglycosylated	1441:1455	arg1	Asn-287					1457:1463	the nonglycosylated Asn-287	1437:1463	the nonglycosylated Asn-287	1437:1463	Replacing the nonglycosylated Asn-287 with glutamine or alanine resulted in protein misfolding and aggregation, leading to retention in the endoplasmic reticulum.
30566828	10	62	theme	CTRP12	1253:1258	arg1	cleavage					1260:1267	CTRP12 cleavage	1253:1267	CTRP12 cleavage	1253:1267	Both Asn-39 and Asn-297 contributed independently to CTRP12 cleavage: maximum cleavage was observed in the double mutant.
30566828	9	63	gly	nonglycosylated	1118:1132	arg1	Asn-297					1134:1140	the nonglycosylated Asn-297	1114:1140	the nonglycosylated Asn-297	1114:1140	Replacing the nonglycosylated Asn-297 with glutamine or alanine also increased CTRP12 cleavage.
30566828	2	64	theme	full-length	237:247	arg1	protein					249:255	a full-length protein	235:255	a full-length protein	235:255	It circulates in plasma as a full-length protein or as a cleaved isoform generated by furin/PCSK3 cleavage.
30566828	12	65	from	retention	1550:1558	arg1	reticulum					1579:1587	the endoplasmic reticulum	1563:1587	the endoplasmic reticulum	1563:1587	Replacing the nonglycosylated Asn-287 with glutamine or alanine resulted in protein misfolding and aggregation, leading to retention in the endoplasmic reticulum.
30566828	12	66	dep	protein	1503:1509	arg1	aggregation					1526:1536	aggregation	1526:1536	aggregation	1526:1536	Replacing the nonglycosylated Asn-287 with glutamine or alanine resulted in protein misfolding and aggregation, leading to retention in the endoplasmic reticulum.
30566828	12	66	dep	protein	1503:1509	arg1	misfolding					1511:1520	misfolding	1511:1520	misfolding	1511:1520	Replacing the nonglycosylated Asn-287 with glutamine or alanine resulted in protein misfolding and aggregation, leading to retention in the endoplasmic reticulum.
29512051	3	0	theme	putative	745:752	arg1	epitopes					754:761	the putative epitopes	741:761	the putative epitopes that appeared to span regions containing N-linked glycans	741:819	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	8	1	theme	kind	1525:1528	arg1	study					1499:1503	This study	1494:1503	This study	1494:1503	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	8	1	theme	kind	1525:1528	arg1	first					1512:1516	first	1512:1516	first	1512:1516	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	6	2	theme	binding	1324:1330	arg1	ELISA					1332:1336	a noncompetitive binding ELISA	1307:1336	a noncompetitive binding ELISA	1307:1336	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	1	3	theme	spectrometry	232:243	arg1	techniques					250:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques	187:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data	187:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	6	4	theme	antigen	1211:1217	arg1	structure					1227:1235	the antigen crystal structure	1207:1235	the antigen crystal structure	1207:1235	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	1	5	theme	MS	246:247	arg1	techniques					250:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques	187:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data	187:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	5	6	gly	Deglycosylation	988:1002	arg1	antigen					1011:1017	the antigen	1007:1017	the antigen	1007:1017	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	7	7	theme	footprinting-MS	1466:1480	arg1	techniques					1482:1491	the two footprinting-MS techniques	1458:1491	the two footprinting-MS techniques	1458:1491	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	3	8	theme	N-linked	804:811	arg1	glycans					813:819	N-linked glycans	804:819	N-linked glycans	804:819	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	8	9	theme	antibody-antigen	1640:1655	arg1	interactions					1665:1676	the monoclonal antibody-antigen binding interactions	1625:1676	the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA	1625:1746	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	1	10	theme	epitope	160:166	arg1	data					176:179	epitope mapping data	160:179	epitope mapping data	160:179	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	6	11	theme	spatial	1274:1280	arg1	orientation					1282:1292	an approximate 90° relative spatial orientation	1246:1292	an approximate 90° relative spatial orientation	1246:1292	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	3	12	contain	containing	793:802	arg1	regions					785:791	regions	785:791	regions containing N-linked glycans	785:819	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	3	12	contain	containing	793:802	arg2	glycans					813:819	N-linked glycans	804:819	N-linked glycans	804:819	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	8	13	theme	bottom-up	1550:1558	arg1	techniques					1576:1585	multiple bottom-up footprinting-MS techniques	1541:1585	multiple bottom-up footprinting-MS techniques	1541:1585	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	7	14	theme	similar	1412:1418	arg1	orientation					1428:1438	a similar binding orientation	1410:1438	a similar binding orientation as predicted from the two footprinting-MS techniques	1410:1491	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	1	15	theme	sandwich	383:390	arg1	ELISA					427:431	ELISA	427:431	ELISA	427:431	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	15	theme	sandwich	383:390	arg1	assay					420:424	a sandwich enzyme-linked immunosorbant assay	381:424	a sandwich enzyme-linked immunosorbant assay (ELISA)	381:432	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	16	theme	multiple	187:194	arg1	techniques					250:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques	187:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data	187:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	2	17	theme	labeling	556:563	arg1	suppression					541:551	suppression	541:551	suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA	541:660	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	1	18	theme	immunosorbant	406:418	arg1	ELISA					427:431	ELISA	427:431	ELISA	427:431	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	18	theme	immunosorbant	406:418	arg1	assay					420:424	a sandwich enzyme-linked immunosorbant assay	381:424	a sandwich enzyme-linked immunosorbant assay (ELISA)	381:432	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	19	theme	labeling	205:212	arg1	techniques					250:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques	187:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data	187:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	8	20	theme	TEM	1591:1593	arg1	visualization					1595:1607	TEM visualization	1591:1607	TEM visualization	1591:1607	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	4	21	theme	structural	836:845	arg1	spectrometry					899:910	carboxyl group footprinting-mass spectrometry	866:910	carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling	866:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	21	theme	structural	836:845	arg1	technique					855:863	An additional structural mapping technique	822:863	An additional structural mapping technique	822:863	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	0	22	theme	Electron	127:134	arg1	Microscopy					136:145	Transmission Electron Microscopy	114:145	Transmission Electron Microscopy	114:145	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	5	23	theme	antigen	1152:1158	arg1	binding					1160:1166	antigen binding	1152:1166	antigen binding	1152:1166	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	5	24	theme	potency	1039:1045	arg1	loss					1031:1034	loss	1031:1034	loss of potency in the ELISA	1031:1058	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	2	25	theme	footprinting-MS	456:470	arg1	data					472:475	Our hydroxyl radical footprinting-MS data	435:475	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP)	435:529	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	2	26	theme	hydroxyl	439:446	arg1	radical					448:454	Our hydroxyl radical	435:454	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP)	435:529	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	6	27	theme	90°	1261:1263	arg1	orientation					1282:1292	an approximate 90° relative spatial orientation	1246:1292	an approximate 90° relative spatial orientation	1246:1292	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	2	28	theme	photochemical	488:500	arg1	oxidation					502:510	fast photochemical oxidation	483:510	fast photochemical oxidation of proteins (FPOP)	483:529	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	0	29	theme	ELISA	20:24	arg1	Interaction					43:53	ELISA Antibody-Antigen Interaction	20:53	ELISA Antibody-Antigen Interaction	20:53	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	7	30	theme	diamond	1370:1376	arg1	complexes					1395:1403	both linear and diamond antibody-antigen complexes	1354:1403	both linear and diamond antibody-antigen complexes	1354:1403	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	1	31	link	enzyme-linked	392:404	arg1	ELISA					427:431	ELISA	427:431	ELISA	427:431	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	31	link	enzyme-linked	392:404	arg1	assay					420:424	a sandwich enzyme-linked immunosorbant assay	381:424	a sandwich enzyme-linked immunosorbant assay (ELISA)	381:432	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	0	32	theme	Interaction	43:53	arg1	Characterization					0:15	Characterization	0:15	Characterization of ELISA Antibody-Antigen Interaction	0:53	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	1	33	theme	antibody-antigen	348:363	arg1	interactions					365:376	the antibody-antigen interactions	344:376	the antibody-antigen interactions	344:376	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	7	34	theme	linear	1359:1364	arg1	complexes					1395:1403	both linear and diamond antibody-antigen complexes	1354:1403	both linear and diamond antibody-antigen complexes	1354:1403	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	8	35	theme	critical	1681:1688	arg1	reagents					1690:1697	critical reagents	1681:1697	critical reagents used in a quality control (QC) lot-release ELISA	1681:1746	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	3	36	theme	blot	697:700	arg1	analysis					702:709	Western blot analysis	689:709	Western blot analysis	689:709	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	4	37	theme	ethyl	926:930	arg1	GEE					939:941	GEE	939:941	GEE	939:941	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	37	theme	ethyl	926:930	arg1	ester					932:936	glycine ethyl ester	918:936	glycine ethyl ester (GEE) labeling	918:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	0	38	theme	Footprinting-Mass	61:77	arg1	Spectrometry					79:90	Footprinting-Mass Spectrometry	61:90	Footprinting-Mass Spectrometry	61:90	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	5	39	theme	labeling	1089:1096	arg1	data					1098:1101	the FPOP and GEE labeling data	1072:1101	data	1098:1101	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	6	40	theme	approximate	1249:1259	arg1	orientation					1282:1292	an approximate 90° relative spatial orientation	1246:1292	an approximate 90° relative spatial orientation	1246:1292	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	4	41	theme	carboxyl	866:873	arg1	spectrometry					899:910	carboxyl group footprinting-mass spectrometry	866:910	carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling	866:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	41	theme	carboxyl	866:873	arg1	technique					855:863	An additional structural mapping technique	822:863	An additional structural mapping technique	822:863	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	5	42	from	loss	1031:1034	arg1	ELISA					1054:1058	the ELISA	1050:1058	the ELISA	1050:1058	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	1	43	theme	negative	274:281	arg1	TEM					323:325	TEM	323:325	TEM	323:325	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	43	theme	negative	274:281	arg1	microscopy					311:320	negative stain transmission electron microscopy	274:320	negative stain transmission electron microscopy (TEM) data	274:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	7	44	theme	TEM	1339:1341	arg1	data					1343:1346	TEM data	1339:1346	TEM data	1339:1346	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	4	45	theme	footprinting-mass	881:897	arg1	spectrometry					899:910	carboxyl group footprinting-mass spectrometry	866:910	carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling	866:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	45	theme	footprinting-mass	881:897	arg1	technique					855:863	An additional structural mapping technique	822:863	An additional structural mapping technique	822:863	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	1	46	theme	transmission	289:300	arg1	TEM					323:325	TEM	323:325	TEM	323:325	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	46	theme	transmission	289:300	arg1	microscopy					311:320	negative stain transmission electron microscopy	274:320	negative stain transmission electron microscopy (TEM) data	274:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	47	theme	microscopy	311:320	arg1	data					328:331	negative stain transmission electron microscopy (TEM) data	274:331	negative stain transmission electron microscopy (TEM) data	274:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	9	48	theme	Graphical	1749:1757	arg1	Abstract					1759:1766	Graphical Abstract	1749:1766	Graphical Abstract	1749:1766	Graphical Abstract ᅟ.
29512051	3	49	theme	epitopes	754:761	arg1	identification					723:736	the identification	719:736	the identification of the putative epitopes that appeared to span regions containing N-linked glycans	719:819	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	8	50	theme	lot-release	1730:1740	arg1	ELISA					1742:1746	a quality control (QC) lot-release ELISA	1707:1746	a quality control (QC) lot-release ELISA	1707:1746	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	1	51	theme	footprinting-mass	214:230	arg1	techniques					250:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques	187:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data	187:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	4	52	theme	ester	932:936	arg1	labeling					944:951	glycine ethyl ester (GEE) labeling	918:951	glycine ethyl ester (GEE) labeling	918:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	6	53	theme	crystal	1219:1225	arg1	structure					1227:1235	the antigen crystal structure	1207:1235	the antigen crystal structure	1207:1235	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	6	54	theme	noncompetitive	1309:1322	arg1	ELISA					1332:1336	a noncompetitive binding ELISA	1307:1336	a noncompetitive binding ELISA	1307:1336	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	2	55	theme	monoclonal	611:620	arg1	mAbs					634:637	mAbs	634:637	mAbs	634:637	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	2	55	theme	monoclonal	611:620	arg1	antibodies					622:631	the monoclonal antibodies	607:631	the monoclonal antibodies (mAbs) utilized in the ELISA	607:660	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	6	56	theme	epitopes	1193:1200	arg1	mapping					1178:1184	mapping	1178:1184	mapping of the epitopes onto the antigen crystal structure	1178:1235	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	7	57	dep	orientation	1428:1438	arg1	predicted					1443:1451	predicted	1443:1451	predicted from the two footprinting-MS techniques	1443:1491	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	6	58	theme	optimal	1295:1301	arg1	orientation					1282:1292	an approximate 90° relative spatial orientation	1246:1292	an approximate 90° relative spatial orientation	1246:1292	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	8	59	theme	multiple	1541:1548	arg1	techniques					1576:1585	multiple bottom-up footprinting-MS techniques	1541:1585	multiple bottom-up footprinting-MS techniques	1541:1585	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	1	60	theme	mapping	168:174	arg1	data					176:179	epitope mapping data	160:179	epitope mapping data	160:179	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	5	61	link	N-linked	1117:1124	arg1	glycans					1126:1132	N-linked glycans	1117:1132	N-linked glycans	1117:1132	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	8	62	theme	footprinting-MS	1560:1574	arg1	techniques					1576:1585	multiple bottom-up footprinting-MS techniques	1541:1585	multiple bottom-up footprinting-MS techniques	1541:1585	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	6	63	theme	relative	1265:1272	arg1	orientation					1282:1292	an approximate 90° relative spatial orientation	1246:1292	an approximate 90° relative spatial orientation	1246:1292	Finally, mapping of the epitopes onto the antigen crystal structure revealed an approximate 90° relative spatial orientation, optimal for a noncompetitive binding ELISA.
29512051	3	64	link	N-linked	804:811	arg1	glycans					813:819	N-linked glycans	804:819	N-linked glycans	804:819	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	0	65	theme	Negative	96:103	arg1	Staining					105:112	Negative Staining	96:112	Negative Staining	96:112	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	5	66	theme	N-linked	1117:1124	arg1	glycans					1126:1132	N-linked glycans	1117:1132	N-linked glycans	1117:1132	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	7	67	theme	binding	1420:1426	arg1	orientation					1428:1438	a similar binding orientation	1410:1438	a similar binding orientation as predicted from the two footprinting-MS techniques	1410:1491	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	0	68	theme	Transmission	114:125	arg1	Microscopy					136:145	Transmission Electron Microscopy	114:145	Transmission Electron Microscopy	114:145	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	1	69	theme	enzyme-linked	392:404	arg1	ELISA					427:431	ELISA	427:431	ELISA	427:431	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	69	theme	enzyme-linked	392:404	arg1	assay					420:424	a sandwich enzyme-linked immunosorbant assay	381:424	a sandwich enzyme-linked immunosorbant assay (ELISA)	381:432	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	70	theme	covalent	196:203	arg1	techniques					250:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques	187:259	multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data	187:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	4	71	theme	additional	825:834	arg1	spectrometry					899:910	carboxyl group footprinting-mass spectrometry	866:910	carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling	866:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	71	theme	additional	825:834	arg1	technique					855:863	An additional structural mapping technique	822:863	An additional structural mapping technique	822:863	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	8	72	theme	monoclonal	1629:1638	arg1	interactions					1665:1676	the monoclonal antibody-antigen binding interactions	1625:1676	the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA	1625:1746	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	4	73	theme	mapping	847:853	arg1	spectrometry					899:910	carboxyl group footprinting-mass spectrometry	866:910	carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling	866:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	73	theme	mapping	847:853	arg1	technique					855:863	An additional structural mapping technique	822:863	An additional structural mapping technique	822:863	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	2	74	theme	radical	448:454	arg1	data					472:475	Our hydroxyl radical footprinting-MS data	435:475	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP)	435:529	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	5	75	theme	antigen	1011:1017	arg1	Deglycosylation					988:1002	Deglycosylation	988:1002	Deglycosylation of the antigen	988:1017	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	7	76	theme	antibody-antigen	1378:1393	arg1	complexes					1395:1403	both linear and diamond antibody-antigen complexes	1354:1403	both linear and diamond antibody-antigen complexes	1354:1403	TEM data shows both linear and diamond antibody-antigen complexes with a similar binding orientation as predicted from the two footprinting-MS techniques.
29512051	2	77	theme	proteins	515:522	arg1	oxidation					502:510	fast photochemical oxidation	483:510	fast photochemical oxidation of proteins (FPOP)	483:529	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	8	78	theme	binding	1657:1663	arg1	interactions					1665:1676	the monoclonal antibody-antigen binding interactions	1625:1676	the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA	1625:1746	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	0	79	theme	Antibody-Antigen	26:41	arg1	Interaction					43:53	ELISA Antibody-Antigen Interaction	20:53	ELISA Antibody-Antigen Interaction	20:53	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	4	80	used	used	958:961	arg2	technique					855:863	An additional structural mapping technique	822:863	An additional structural mapping technique	822:863	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	80	used	used	958:961	arg2	spectrometry					899:910	carboxyl group footprinting-mass spectrometry	866:910	carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling	866:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	2	81	theme	fast	483:486	arg1	oxidation					502:510	fast photochemical oxidation	483:510	fast photochemical oxidation of proteins (FPOP)	483:529	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	0	82	dep	Spectrometry	79:90	arg1	Microscopy					136:145	Transmission Electron Microscopy	114:145	Transmission Electron Microscopy	114:145	Characterization of ELISA Antibody-Antigen Interaction using Footprinting-Mass Spectrometry and Negative Staining Transmission Electron Microscopy.
29512051	8	83	theme	reagents	1690:1697	arg1	interactions					1665:1676	the monoclonal antibody-antigen binding interactions	1625:1676	the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA	1625:1746	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	3	84	theme	Western	689:695	arg1	analysis					702:709	Western blot analysis	689:709	Western blot analysis	689:709	Combining these data with Western blot analysis enabled the identification of the putative epitopes that appeared to span regions containing N-linked glycans.
29512051	2	85	dep	labeling	556:563	arg1	either					597:602	either	597:602	either	597:602	Our hydroxyl radical footprinting-MS data using fast photochemical oxidation of proteins (FPOP) indicates suppression of labeling across the antigen upon binding either of the monoclonal antibodies (mAbs) utilized in the ELISA.
29512051	5	86	theme	GEE	1085:1087	arg1	data					1098:1101	the FPOP and GEE labeling data	1072:1101	data	1098:1101	Deglycosylation of the antigen resulted in loss of potency in the ELISA, supporting the FPOP and GEE labeling data by indicating N-linked glycans are necessary for antigen binding.
29512051	4	87	theme	glycine	918:924	arg1	GEE					939:941	GEE	939:941	GEE	939:941	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	87	theme	glycine	918:924	arg1	ester					932:936	glycine ethyl ester	918:936	glycine ethyl ester (GEE) labeling	918:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	8	88	theme	quality	1709:1715	arg1	control					1717:1723	quality control	1709:1723	quality control (QC)	1709:1728	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	8	88	theme	quality	1709:1715	arg1	QC					1726:1727	QC	1726:1727	QC	1726:1727	This study is the first of its kind to utilize multiple bottom-up footprinting-MS techniques and TEM visualization to characterize the monoclonal antibody-antigen binding interactions of critical reagents used in a quality control (QC) lot-release ELISA.
29512051	1	89	theme	stain	283:287	arg1	TEM					323:325	TEM	323:325	TEM	323:325	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	89	theme	stain	283:287	arg1	microscopy					311:320	negative stain transmission electron microscopy	274:320	negative stain transmission electron microscopy (TEM) data	274:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	4	90	theme	group	875:879	arg1	spectrometry					899:910	carboxyl group footprinting-mass spectrometry	866:910	carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling	866:951	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	4	90	theme	group	875:879	arg1	technique					855:863	An additional structural mapping technique	822:863	An additional structural mapping technique	822:863	An additional structural mapping technique, carboxyl group footprinting-mass spectrometry using glycine ethyl ester (GEE) labeling, was used to confirm the epitopes.
29512051	1	91	theme	electron	302:309	arg1	TEM					323:325	TEM	323:325	TEM	323:325	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
29512051	1	91	theme	electron	302:309	arg1	microscopy					311:320	negative stain transmission electron microscopy	274:320	negative stain transmission electron microscopy (TEM) data	274:331	We describe epitope mapping data using multiple covalent labeling footprinting-mass spectrometry (MS) techniques coupled with negative stain transmission electron microscopy (TEM) data to analyze the antibody-antigen interactions in a sandwich enzyme-linked immunosorbant assay (ELISA).
31362688	0	0	theme	Novel	94:98	arg1	Gene					100:103	the Candidate Novel Gene GALNT14	80:111	the Candidate Novel Gene GALNT14	80:111	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	8	1	link	O-linked	887:894	arg1	biosynthesis					912:923	O-linked oligosaccharide biosynthesis	887:923	O-linked oligosaccharide biosynthesis	887:923	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	5	2	theme	gene	604:607	arg1	Nacetylgalactosaminyltransferase					609:640	gene Nacetylgalactosaminyltransferase 14	604:643	the gene Nacetylgalactosaminyltransferase 14 (GALNT14)	600:653	Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14).
31362688	5	2	theme	gene	604:607	arg1	GALNT14					646:652	GALNT14	646:652	GALNT14	646:652	Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14).
31362688	4	3	dep	NM_001253826.1	543:556	arg1	c.60delC					558:565	c.60delC	558:565	The Homozygous frameshift variant NM_001253826.1:c.60delC	509:565	The Homozygous frameshift variant NM_001253826.1:c.60delC;p.
31362688	0	4	theme	Candidate	84:92	arg1	Gene					100:103	the Candidate Novel Gene GALNT14	80:111	the Candidate Novel Gene GALNT14	80:111	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	8	5	theme	N-acetyl-D-	945:955	arg1	residue					971:977	an N-acetyl-D- galactosamine residue	942:977	an N-acetyl-D- galactosamine residue	942:977	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	8	6	theme	target	1015:1020	arg1	proteins					1022:1029	target proteins	1015:1029	target proteins especially Mucins	1015:1047	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	3	7	from	sibs	476:479	arg1	family					501:506	a consanguineous family	484:506	a consanguineous family	484:506	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	3	8	used	used	405:408	arg2	we					402:403	we	402:403	we	402:403	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	2	9	theme	contribution	307:318	arg1	evidence					287:294	the strong evidence	276:294	the strong evidence of genetic contribution in KC	276:324	Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases.
31362688	0	10	from	Variant	69:75	arg1	Gene					100:103	the Candidate Novel Gene GALNT14	80:111	the Candidate Novel Gene GALNT14	80:111	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	3	11	dep	METHODS	379:385	arg1	used					405:408	used	405:408	used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family	405:506	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	8	12	theme	residue	971:977	arg1	transfer					930:937	the transfer	926:937	the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins	926:1047	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	3	13	theme	KC	466:467	arg1	cause					457:461	the genetic cause	445:461	the genetic cause of KC in two sibs in a consanguineous family	445:506	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	8	14	theme	galactosamine	957:969	arg1	residue					971:977	an N-acetyl-D- galactosamine residue	942:977	an N-acetyl-D- galactosamine residue	942:977	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	3	15	theme	consanguineous	486:499	arg1	family					501:506	a consanguineous family	484:506	a consanguineous family	484:506	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	7	16	theme	candidate	822:830	arg1	gene					832:835	the candidate gene	818:835	the candidate gene	818:835	Moreover, no database harbours homozygous loss of function variants in the candidate gene.
31362688	1	17	theme	noninflammatory	164:178	arg1	ectasia					200:206	noninflammatory progressive corneal ectasia	164:206	noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical	164:265	BACKGROUND Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical.
31362688	3	18	from	cause	457:461	arg1	sibs					476:479	two sibs	472:479	two sibs in a consanguineous family	472:506	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	2	19	theme	strong	280:285	arg1	evidence					287:294	the strong evidence	276:294	the strong evidence of genetic contribution in KC	276:324	Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases.
31362688	7	20	theme	variants	806:813	arg1	loss					789:792	homozygous loss	778:792	homozygous loss of function variants in the candidate gene	778:835	Moreover, no database harbours homozygous loss of function variants in the candidate gene.
31362688	1	21	theme	progressive	180:190	arg1	ectasia					200:206	noninflammatory progressive corneal ectasia	164:206	noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical	164:265	BACKGROUND Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical.
31362688	0	22	theme	Recessive	10:18	arg1	Keratoconus					34:44	Autosomal Recessive Non-syndromic Keratoconus	0:44	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.	0:112	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	8	23	from	threonine	994:1002	arg1	proteins					1022:1029	target proteins	1015:1029	target proteins especially Mucins	1015:1047	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	1	24	dep	bilateral	153:161	arg1	ectasia					200:206	noninflammatory progressive corneal ectasia	164:206	noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical	164:265	BACKGROUND Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical.
31362688	1	25	theme	corneal	192:198	arg1	ectasia					200:206	noninflammatory progressive corneal ectasia	164:206	noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical	164:265	BACKGROUND Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical.
31362688	0	26	theme	Autosomal	0:8	arg1	Keratoconus					34:44	Autosomal Recessive Non-syndromic Keratoconus	0:44	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.	0:112	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	4	27	theme	frameshift	524:533	arg1	NM_001253826.1					543:556	The Homozygous frameshift variant NM_001253826.1	509:556	The Homozygous frameshift variant NM_001253826.1:c.60delC	509:565	The Homozygous frameshift variant NM_001253826.1:c.60delC;p.
31362688	2	28	theme	most	367:370	arg1	cases					372:376	most cases	367:376	most cases	367:376	Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases.
31362688	4	29	theme	Homozygous	513:522	arg1	NM_001253826.1					543:556	The Homozygous frameshift variant NM_001253826.1	509:556	The Homozygous frameshift variant NM_001253826.1:c.60delC	509:565	The Homozygous frameshift variant NM_001253826.1:c.60delC;p.
31362688	6	30	theme	exome	731:735	arg1	database					737:744	our internal exome database	718:744	our internal exome database	718:744	The variant does not exist in all public databases neither in our internal exome database.
31362688	7	31	theme	function	797:804	arg1	variants					806:813	function variants	797:813	function variants	797:813	Moreover, no database harbours homozygous loss of function variants in the candidate gene.
31362688	0	32	theme	Non-syndromic	20:32	arg1	Keratoconus					34:44	Autosomal Recessive Non-syndromic Keratoconus	0:44	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.	0:112	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	8	33	dep	serine	984:989	arg1	a					982:982	a	982:982	a	982:982	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	8	33	dep	serine	984:989	arg1	residue					1004:1010	residue	1004:1010	residue	1004:1010	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	4	34	dep	p	567:567	arg1	NM_001253826.1					543:556	The Homozygous frameshift variant NM_001253826.1	509:556	The Homozygous frameshift variant NM_001253826.1:c.60delC	509:565	The Homozygous frameshift variant NM_001253826.1:c.60delC;p.
31362688	1	35	theme	BACKGROUND	114:123	arg1	KC					138:139	KC	138:139	KC	138:139	BACKGROUND Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical.
31362688	1	35	theme	BACKGROUND	114:123	arg1	Keratoconus					125:135	BACKGROUND Keratoconus	114:135	BACKGROUND Keratoconus (KC)	114:140	BACKGROUND Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical.
31362688	7	36	theme	homozygous	778:787	arg1	loss					789:792	homozygous loss	778:792	homozygous loss of function variants in the candidate gene	778:835	Moreover, no database harbours homozygous loss of function variants in the candidate gene.
31362688	3	37	theme	genetic	449:455	arg1	cause					457:461	the genetic cause	445:461	the genetic cause of KC in two sibs in a consanguineous family	445:506	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	0	38	theme	Homozygous	47:56	arg1	Variant					69:75	Homozygous Frameshift Variant	47:75	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.	0:112	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	4	39	theme	variant	535:541	arg1	NM_001253826.1					543:556	The Homozygous frameshift variant NM_001253826.1	509:556	The Homozygous frameshift variant NM_001253826.1:c.60delC	509:565	The Homozygous frameshift variant NM_001253826.1:c.60delC;p.
31362688	8	40	theme	O-linked	887:894	arg1	biosynthesis					912:923	O-linked oligosaccharide biosynthesis	887:923	O-linked oligosaccharide biosynthesis	887:923	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	9	41	theme	truncated	1197:1205	arg1	GALNT14					1215:1221	the truncated protein GALNT14	1193:1221	the truncated protein GALNT14	1193:1221	CONCLUSION As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
31362688	8	42	theme	initial	867:873	arg1	reaction					875:882	the initial reaction	863:882	the initial reaction	863:882	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	3	43	theme	whole-exome	410:420	arg1	sequencing					422:431	whole-exome sequencing	410:431	whole-exome sequencing	410:431	METHODS In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family.
31362688	9	44	theme	protein	1207:1213	arg1	GALNT14					1215:1221	the truncated protein GALNT14	1193:1221	the truncated protein GALNT14	1193:1221	CONCLUSION As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
31362688	7	45	from	loss	789:792	arg1	gene					832:835	the candidate gene	818:835	the candidate gene	818:835	Moreover, no database harbours homozygous loss of function variants in the candidate gene.
31362688	6	46	theme	internal	722:729	arg1	database					737:744	our internal exome database	718:744	our internal exome database	718:744	The variant does not exist in all public databases neither in our internal exome database.
31362688	9	47	theme	eye	1127:1129	arg1	diseases					1131:1138	eye diseases	1127:1138	eye diseases	1127:1138	CONCLUSION As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
31362688	9	48	attach	linked	1105:1110	arg1	number					1117:1122	a number	1115:1122	a number of eye diseases	1115:1138	CONCLUSION As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
31362688	9	48	attach	linked	1105:1110	arg2	alterations					1064:1074	alterations	1064:1074	alterations of mucin's glycosylation	1064:1099	CONCLUSION As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
31362688	2	49	theme	KC	343:344	arg1	etiology					331:338	the etiology	327:338	the etiology of KC	327:344	Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases.
31362688	0	50	theme	Frameshift	58:67	arg1	Variant					69:75	Homozygous Frameshift Variant	47:75	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.	0:112	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	9	51	dep	CONCLUSION	1050:1059	arg1	linked					1105:1110	linked	1105:1110	are linked to a number of eye diseases	1101:1138	CONCLUSION As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
31362688	2	52	from	evidence	287:294	arg1	KC					323:324	KC	323:324	KC	323:324	Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases.
31362688	0	53	dep	Keratoconus	34:44	arg1	Variant					69:75	Homozygous Frameshift Variant	47:75	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.	0:112	Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14.
31362688	5	54	theme	Leu21Cysfs	569:578	arg1	*					579:579	Leu21Cysfs*6	569:580	Leu21Cysfs*6	569:580	Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14).
31362688	8	55	dep	proteins	1022:1029	arg1	Mucins					1042:1047	Mucins	1042:1047	target proteins especially Mucins	1015:1047	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	8	56	theme	oligosaccharide	896:910	arg1	biosynthesis					912:923	O-linked oligosaccharide biosynthesis	887:923	O-linked oligosaccharide biosynthesis	887:923	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
31362688	2	57	theme	genetic	299:305	arg1	contribution					307:318	genetic contribution	299:318	genetic contribution	299:318	Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases.
31362688	6	58	dep	databases	697:705	arg1	neither					707:713	neither	707:713	neither	707:713	The variant does not exist in all public databases neither in our internal exome database.
31362688	6	59	theme	public	690:695	arg1	databases					697:705	all public databases	686:705	all public databases	686:705	The variant does not exist in all public databases neither in our internal exome database.
31362688	9	60	theme	diseases	1131:1138	arg1	number					1117:1122	a number	1115:1122	a number of eye diseases	1115:1138	CONCLUSION As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
31362688	8	61	from	serine	984:989	arg1	proteins					1022:1029	target proteins	1015:1029	target proteins especially Mucins	1015:1047	RESULT GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
30655169	3	0	theme	process	529:535	arg1	parameters					501:510	parameters	501:510	parameters of manufacturing process	501:535	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	3	0	theme	process	529:535	arg1	cell					492:495	producer cell	483:495	producer cell	483:495	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	2	1	from	effector	292:299	arg1	functions					315:323	Fc-related functions	304:323	Fc-related functions	304:323	IgG1 subclass is the most potent effector in Fc-related functions.
30655169	4	2	theme	cultivation	619:629	arg1	changes					641:647	cultivation selective changes	619:647	cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar	619:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	5	3	theme	mAb	832:834	arg1	binding					817:823	binding	817:823	binding of the mAb to its antigen	817:849	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	5	4	theme	cellular	948:955	arg1	ADCC					971:974	ADCC	971:974	ADCC	971:974	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	5	4	theme	cellular	948:955	arg1	cytotoxicity					957:968	antibody dependent cellular cytotoxicity	929:968	antibody dependent cellular cytotoxicity (ADCC)	929:975	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	5	5	from	process	768:774	arg1	such					748:751	such	748:751	such	748:751	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	0	6	theme	IgG1/FcγR	99:107	arg1	interaction					109:119	IgG1/FcγR interaction	99:119	IgG1/FcγR interaction	99:119	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	2	7	theme	potent	285:290	arg1	effector					292:299	the most potent effector	276:299	the most potent effector in Fc-related functions	276:323	IgG1 subclass is the most potent effector in Fc-related functions.
30655169	2	7	theme	potent	285:290	arg1	subclass					264:271	IgG1 subclass	259:271	IgG1 subclass	259:271	IgG1 subclass is the most potent effector in Fc-related functions.
30655169	5	8	from	such	748:751	arg1	process					768:774	cultivation process	756:774	cultivation process	756:774	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	5	9	theme	dependent	938:946	arg1	ADCC					971:974	ADCC	971:974	ADCC	971:974	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	5	9	theme	dependent	938:946	arg1	cytotoxicity					957:968	antibody dependent cellular cytotoxicity	929:968	antibody dependent cellular cytotoxicity (ADCC)	929:975	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	4	10	theme	selective	631:639	arg1	changes					641:647	cultivation selective changes	619:647	cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar	619:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	5	11	theme	galactosylation	785:799	arg1	shift					776:780	such in cultivation process shift	748:780	such in cultivation process shift of galactosylation	748:799	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	5	12	theme	Fcγ	892:894	arg1	receptors					896:904	Fcγ receptors	892:904	Fcγ receptors	892:904	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	3	13	theme	mAbs	356:359	arg1	glycosylation					339:351	The N-linked glycosylation	326:351	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification	326:457	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	3	13	theme	mAbs	356:359	arg1	dependent					470:478	dependent	470:478	dependent	470:478	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	5	14	with	interaction	864:874	arg1	receptors					896:904	Fcγ receptors	892:904	Fcγ receptors	892:904	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	4	15	theme	IgG1	697:700	arg1	biosimilar					715:724	a model therapeutic mAb IgG1, trastuzumab biosimilar	673:724	biosimilar	715:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	3	16	theme	therapeutic	400:410	arg1	activity					412:419	its therapeutic activity	396:419	its therapeutic activity	396:419	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	4	17	theme	biosimilar	715:724	arg1	content					662:668	galactose content	652:668	galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar	652:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	2	18	theme	Fc-related	304:313	arg1	functions					315:323	Fc-related functions	304:323	Fc-related functions	304:323	IgG1 subclass is the most potent effector in Fc-related functions.
30655169	3	19	theme	modification	446:457	arg1	activity					412:419	its therapeutic activity	396:419	its therapeutic activity	396:419	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	3	19	theme	modification	446:457	arg1	presence					429:436	the presence	425:436	the presence of this modification	425:457	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	0	20	theme	IgG	23:25	arg1	antibodies					27:36	therapeutic IgG antibodies	11:36	therapeutic IgG antibodies	11:36	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	4	21	theme	culture	578:584	arg1	conditions					586:595	cell culture conditions	573:595	cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar	573:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	5	22	theme	such	748:751	arg1	shift					776:780	such in cultivation process shift	748:780	such in cultivation process shift of galactosylation	748:799	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	3	23	link	N-linked	330:337	arg1	glycosylation					339:351	The N-linked glycosylation	326:351	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification	326:457	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	3	23	link	N-linked	330:337	arg1	dependent					470:478	dependent	470:478	dependent	470:478	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	3	24	theme	producer	483:490	arg1	cell					492:495	producer cell	483:495	producer cell	483:495	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	0	25	theme	therapeutic	11:21	arg1	antibodies					27:36	therapeutic IgG antibodies	11:36	therapeutic IgG antibodies	11:36	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	0	26	theme	ADCC	125:128	arg1	activity					130:137	ADCC activity	125:137	ADCC activity	125:137	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	0	27	from	impact	89:94	arg1	interaction					109:119	IgG1/FcγR interaction	99:119	IgG1/FcγR interaction	99:119	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	0	27	from	impact	89:94	arg1	activity					130:137	ADCC activity	125:137	ADCC activity	125:137	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	1	28	theme	growing	204:210	arg1	pharmaceuticals					221:235	pharmaceuticals	221:235	pharmaceuticals	221:235	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	1	28	theme	growing	204:210	arg1	group					212:216	the fastest growing group	192:216	the fastest growing group of pharmaceuticals on the global market	192:256	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	5	29	theme	cultivation	756:766	arg1	process					768:774	cultivation process	756:774	cultivation process	756:774	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	5	30	theme	mAb	883:885	arg1	interaction					864:874	interaction	864:874	interaction of the mAb with Fcγ receptors	864:904	We demonstrated that such in cultivation process shift of galactosylation does not affect binding of the mAb to its antigen yet modifies interaction of the mAb with Fcγ receptors and therefore enhances antibody dependent cellular cytotoxicity (ADCC).
30655169	4	31	theme	mAb	693:695	arg1	biosimilar					715:724	a model therapeutic mAb IgG1, trastuzumab biosimilar	673:724	biosimilar	715:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	0	32	theme	antibodies	27:36	arg1	Control					0:6	Control	0:6	Control of therapeutic IgG antibodies	0:36	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	3	33	dep	glycosylation	339:351	arg1	influences					385:394	influences	385:394	influences its therapeutic activity and the presence of this modification	385:457	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	1	34	from	group	212:216	arg1	market					251:256	the global market	240:256	the global market	240:256	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	4	35	theme	therapeutic	681:691	arg1	biosimilar					715:724	a model therapeutic mAb IgG1, trastuzumab biosimilar	673:724	biosimilar	715:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	0	36	theme	cultivation	61:71	arg1	process					73:79	cultivation process	61:79	cultivation process	61:79	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	4	37	from	changes	641:647	arg1	content					662:668	galactose content	652:668	galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar	652:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	3	38	gly	glycosylation	339:351	arg1	mAbs					356:359	mAbs	356:359	mAbs	356:359	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	0	39	from	process	73:79	arg1	interaction					109:119	IgG1/FcγR interaction	99:119	IgG1/FcγR interaction	99:119	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	0	39	from	process	73:79	arg1	activity					130:137	ADCC activity	125:137	ADCC activity	125:137	Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity.
30655169	4	40	theme	cell	573:576	arg1	conditions					586:595	cell culture conditions	573:595	cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar	573:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	3	41	theme	manufacturing	515:527	arg1	process					529:535	manufacturing process	515:535	manufacturing process	515:535	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	4	42	dep	biosimilar	715:724	arg1	trastuzumab					703:713	a model therapeutic mAb IgG1, trastuzumab biosimilar	673:724	trastuzumab	703:713	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	1	43	theme	pharmaceuticals	221:235	arg1	pharmaceuticals					221:235	pharmaceuticals	221:235	pharmaceuticals	221:235	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	1	43	theme	pharmaceuticals	221:235	arg1	group					212:216	the fastest growing group	192:216	the fastest growing group of pharmaceuticals on the global market	192:256	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	2	44	theme	IgG1	259:262	arg1	effector					292:299	the most potent effector	276:299	the most potent effector in Fc-related functions	276:323	IgG1 subclass is the most potent effector in Fc-related functions.
30655169	2	44	theme	IgG1	259:262	arg1	subclass					264:271	IgG1 subclass	259:271	IgG1 subclass	259:271	IgG1 subclass is the most potent effector in Fc-related functions.
30655169	1	45	theme	Therapeutic	140:150	arg1	antibodies					163:172	Therapeutic monoclonal antibodies	140:172	Therapeutic monoclonal antibodies (mAbs)	140:179	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	1	45	theme	Therapeutic	140:150	arg1	mAbs					175:178	mAbs	175:178	mAbs	175:178	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	3	46	theme	N-linked	330:337	arg1	glycosylation					339:351	The N-linked glycosylation	326:351	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification	326:457	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	3	46	theme	N-linked	330:337	arg1	dependent					470:478	dependent	470:478	dependent	470:478	The N-linked glycosylation of mAbs Fc-domain significantly influences its therapeutic activity and the presence of this modification is largely dependent on producer cell and parameters of manufacturing process.
30655169	1	47	theme	fastest	196:202	arg1	pharmaceuticals					221:235	pharmaceuticals	221:235	pharmaceuticals	221:235	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	1	47	theme	fastest	196:202	arg1	group					212:216	the fastest growing group	192:216	the fastest growing group of pharmaceuticals on the global market	192:256	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	1	48	theme	monoclonal	152:161	arg1	antibodies					163:172	Therapeutic monoclonal antibodies	140:172	Therapeutic monoclonal antibodies (mAbs)	140:179	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	1	48	theme	monoclonal	152:161	arg1	mAbs					175:178	mAbs	175:178	mAbs	175:178	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30655169	4	49	theme	model	675:679	arg1	biosimilar					715:724	a model therapeutic mAb IgG1, trastuzumab biosimilar	673:724	biosimilar	715:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	4	50	theme	galactose	652:660	arg1	content					662:668	galactose content	652:668	galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar	652:724	Here we examined and characterized cell culture conditions that determine during cultivation selective changes in galactose content of a model therapeutic mAb IgG1, trastuzumab biosimilar.
30655169	1	51	theme	global	244:249	arg1	market					251:256	the global market	240:256	the global market	240:256	Therapeutic monoclonal antibodies (mAbs) are within the fastest growing group of pharmaceuticals on the global market.
30422384	2	0	from	cleavage	452:459	arg1	peptide					537:543	an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide	482:543	peptide	537:543	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	2	0	from	cleavage	452:459	arg1	pro-AT					500:505	pro-AT	500:505	pro-AT	500:505	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	5	1	from	patients	1003:1010	arg1	fluids					970:975	protease-rich synovial fluids	947:975	protease-rich synovial fluids from rheumatoid arthritis patients	947:1010	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	1	2	theme	MMP-9	278:282	arg1	unique					298:303	unique	298:303	unique	298:303	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	1	2	theme	MMP-9	278:282	arg1	propeptide					284:293	The MMP-9 propeptide	274:293	The MMP-9 propeptide	274:293	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	10	3	theme	MMP-9	1707:1711	arg1	activity					1695:1702	the specific activity	1682:1702	the specific activity of MMP-9 in physiology and pathology	1682:1739	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	11	4	theme	meprin	1791:1796	arg1	EC					1800:1801	meprin α EC 3.4.24.18	1791:1811	meprin α EC 3.4.24.18	1791:1811	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	4	theme	meprin	1791:1796	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	4	5	theme	MMP-9	694:698	arg1	propeptide					700:709	the MMP-9 propeptide	690:709	the MMP-9 propeptide by MMP-3 and neutrophil elastase	690:742	First, we report new cleavage sites in the MMP-9 propeptide by MMP-3 and neutrophil elastase.
30422384	0	6	theme	catalytic	222:230	arg1	zinc					232:235	the catalytic zinc	218:235	the catalytic zinc	218:235	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	9	7	theme	proMMP-9	1554:1561	arg1	activation					1563:1572	proMMP-9 activation	1554:1572	proMMP-9 activation	1554:1572	Finally, we demonstrated that glycan-galectin-3 interactions reduced proMMP-9 activation.
30422384	5	8	theme	meprin	910:915	arg1	α					917:917	meprin α	910:917	meprin α	910:917	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	5	8	theme	meprin	910:915	arg1	MMP-3					896:900	MMP-3	896:900	MMP-3	896:900	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	4	9	theme	cleavage	672:679	arg1	sites					681:685	new cleavage sites	668:685	new cleavage sites in the MMP-9 propeptide by MMP-3 and neutrophil elastase	668:742	First, we report new cleavage sites in the MMP-9 propeptide by MMP-3 and neutrophil elastase.
30422384	3	10	gly	glycosylated	625:636	arg1	pro-ATSf-9					638:647	recombinant glycosylated pro-ATSf-9	613:647	recombinant glycosylated pro-ATSf-9	613:647	We chemically synthesized aglycosyl pro-AT and pro-CT and purified recombinant glycosylated pro-ATSf-9 .
30422384	5	11	theme	aglycosyl	856:864	arg1	pro-AT					866:871	aglycosyl pro-AT	856:871	aglycosyl pro-AT	856:871	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	8	12	theme	Glycosylation	1389:1401	arg1	patients					1403:1410	Glycosylation patients	1389:1410	Glycosylation patients	1389:1410	Additionally, proMMP-9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP-3.
30422384	3	13	theme	glycosylated	625:636	arg1	pro-ATSf-9					638:647	recombinant glycosylated pro-ATSf-9	613:647	recombinant glycosylated pro-ATSf-9	613:647	We chemically synthesized aglycosyl pro-AT and pro-CT and purified recombinant glycosylated pro-ATSf-9 .
30422384	8	14	from	Disorder	1377:1384	arg1	proMMP-9					1352:1359	proMMP-9	1352:1359	proMMP-9	1352:1359	Additionally, proMMP-9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP-3.
30422384	5	15	theme	synovial	961:968	arg1	fluids					970:975	protease-rich synovial fluids	947:975	protease-rich synovial fluids from rheumatoid arthritis patients	947:1010	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	2	16	theme	pro-CT	529:534	arg1	peptide					537:543	an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide	482:543	peptide	537:543	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	11	17	theme	trypsin	1848:1854	arg1	EC					1856:1857	trypsin EC 3.4.21.4	1848:1866	trypsin EC 3.4.21.4	1848:1866	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	17	theme	trypsin	1848:1854	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	7	18	theme	proteolytic	1314:1324	arg1	activation					1326:1335	proteolytic activation	1314:1335	proteolytic activation	1314:1335	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	1	19	theme	post-translational	338:355	arg1	modification					357:368	its post-translational modification	334:368	its post-translational modification with an N-linked oligosaccharide	334:401	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	2	20	theme	carboxyterminal	512:526	arg1	peptide					537:543	an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide	482:543	peptide	537:543	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	0	21	theme	proMMP-9/progelatinase	89:110	arg1	activation					69:78	proteolytic activation	57:78	proteolytic activation of human proMMP-9/progelatinase	57:110	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	0	22	theme	MMP	258:260	arg1	activation					262:271	MMP activation	258:271	MMP activation	258:271	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	11	23	theme	PNGase	1872:1877	arg1	EC					1881:1882	PNGase F EC 3.5.1.52	1872:1891	PNGase F EC 3.5.1.52	1872:1891	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	23	theme	PNGase	1872:1877	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	0	24	theme	Matrix	115:120	arg1	metalloproteinases					122:139	B. Matrix metalloproteinases	112:139	B. Matrix metalloproteinases (MMPs)	112:146	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	0	24	theme	Matrix	115:120	arg1	proenzymes					164:173	proenzymes	164:173	proenzymes	164:173	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	0	24	theme	Matrix	115:120	arg1	MMPs					142:145	MMPs	142:145	MMPs	142:145	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	1	25	theme	N-linked	378:385	arg1	oligosaccharide					387:401	an N-linked oligosaccharide	375:401	an N-linked oligosaccharide	375:401	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	8	26	theme	higher	1452:1457	arg1	rate					1470:1473	a higher activation rate	1450:1473	a higher activation rate by MMP-3	1450:1482	Additionally, proMMP-9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP-3.
30422384	7	27	theme	human	1259:1263	arg1	proMMP-9					1276:1283	human neutrophil proMMP-9	1259:1283	human neutrophil proMMP-9	1259:1283	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	2	28	from	pro-AT	500:505	arg1	cleavage					452:459	cleavage	452:459	cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide	452:543	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	6	29	from	effect	1043:1048	arg1	activation					1082:1091	proteolytic activation	1070:1091	proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis	1070:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	0	30	theme	Propeptide	0:9	arg1	glycosylation					11:23	Propeptide glycosylation	0:23	Propeptide glycosylation	0:23	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	2	31	theme	propeptide	468:477	arg1	cleavage					452:459	cleavage	452:459	cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide	452:543	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	10	32	theme	glycosylation	1623:1635	arg1	mechanism					1654:1662	a fine-tuning mechanism	1640:1662	a fine-tuning mechanism	1640:1662	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	10	32	theme	glycosylation	1623:1635	arg1	modification					1590:1601	modification	1590:1601	modification of MMP-9 propeptide glycosylation	1590:1635	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	5	33	theme	pro-AT	866:871	arg1	resistance					822:831	a higher resistance	813:831	a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis	813:891	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	5	34	theme	arthritis	993:1001	arg1	patients					1003:1010	rheumatoid arthritis patients	982:1010	rheumatoid arthritis patients	982:1010	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	6	35	theme	human	1096:1100	arg1	proMMP-9					1102:1109	human proMMP-9	1096:1109	human proMMP-9	1096:1109	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	10	36	theme	MMP-9	1606:1610	arg1	glycosylation					1623:1635	MMP-9 propeptide glycosylation	1606:1635	MMP-9 propeptide glycosylation	1606:1635	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	11	37	theme	neutrophil	1814:1823	arg1	EC					1834:1835	neutrophil elastase EC 3.4.21.37	1814:1845	neutrophil elastase EC 3.4.21.37	1814:1845	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	37	theme	neutrophil	1814:1823	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	5	38	theme	higher	815:820	arg1	resistance					822:831	a higher resistance	813:831	a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis	813:891	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	7	39	theme	proMMP-9	1211:1218	arg1	glycoforms					1220:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	5	40	theme	western	791:797	arg1	analysis					804:811	western blot analysis	791:811	western blot analysis	791:811	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	0	41	theme	proteolytic	57:67	arg1	activation					69:78	proteolytic activation	57:78	proteolytic activation of human proMMP-9/progelatinase	57:110	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	6	42	theme	cleavage	1163:1170	arg1	analysis					1172:1179	cleavage analysis	1163:1179	cleavage analysis	1163:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	10	43	theme	specific	1686:1693	arg1	activity					1695:1702	the specific activity	1682:1702	the specific activity of MMP-9 in physiology and pathology	1682:1739	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	2	44	theme	ProMMP-9	404:411	arg1	activation					413:422	ProMMP-9 activation	404:422	ProMMP-9 activation by MMP-3	404:431	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	6	45	theme	dye-quenched	1142:1153	arg1	gelatin					1155:1161	dye-quenched gelatin	1142:1161	dye-quenched gelatin	1142:1161	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	5	46	theme	blot	799:802	arg1	analysis					804:811	western blot analysis	791:811	western blot analysis	791:811	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	6	47	gly	glycosylation	1053:1065	arg1	proMMP-9					1102:1109	human proMMP-9	1096:1109	human proMMP-9	1096:1109	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	6	48	theme	zymography	1127:1136	arg1	use					1120:1122	the use	1116:1122	the use of zymography and dye-quenched gelatin cleavage analysis	1116:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	1	49	from	family	316:321	arg1	unique					298:303	unique	298:303	unique	298:303	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	1	49	from	family	316:321	arg1	propeptide					284:293	The MMP-9 propeptide	274:293	The MMP-9 propeptide	274:293	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	3	50	theme	aglycosyl	572:580	arg1	pro-AT					582:587	aglycosyl pro-AT	572:587	aglycosyl pro-AT	572:587	We chemically synthesized aglycosyl pro-AT and pro-CT and purified recombinant glycosylated pro-ATSf-9 .
30422384	9	51	theme	glycan-galectin-3	1515:1531	arg1	interactions					1533:1544	glycan-galectin-3 interactions	1515:1544	glycan-galectin-3 interactions	1515:1544	Finally, we demonstrated that glycan-galectin-3 interactions reduced proMMP-9 activation.
30422384	11	52	theme	α	1798:1798	arg1	EC					1800:1801	meprin α EC 3.4.24.18	1791:1811	meprin α EC 3.4.24.18	1791:1811	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	52	theme	α	1798:1798	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	7	53	theme	recombinant	1194:1204	arg1	glycoforms					1220:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	5	54	theme	analysis	804:811	arg1	use					784:786	the use	780:786	the use of western blot analysis	780:811	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	1	55	from	unique	298:303	arg1	family					316:321	the MMP family	308:321	the MMP family	308:321	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	11	56	dep	ENZYMES	1742:1748	arg1	EC					1834:1835	neutrophil elastase EC 3.4.21.37	1814:1845	neutrophil elastase EC 3.4.21.37	1814:1845	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	56	dep	ENZYMES	1742:1748	arg1	EC					1800:1801	meprin α EC 3.4.24.18	1791:1811	meprin α EC 3.4.24.18	1791:1811	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	56	dep	ENZYMES	1742:1748	arg1	EC					1777:1778	MMP-3 EC 3.4.24.17	1771:1788	MMP-3 EC 3.4.24.17	1771:1788	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	56	dep	ENZYMES	1742:1748	arg1	EC					1881:1882	PNGase F EC 3.5.1.52	1872:1891	PNGase F EC 3.5.1.52	1872:1891	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	56	dep	ENZYMES	1742:1748	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	56	dep	ENZYMES	1742:1748	arg1	EC					1856:1857	trypsin EC 3.4.21.4	1848:1866	trypsin EC 3.4.21.4	1848:1866	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	56	dep	ENZYMES	1742:1748	arg1	EC					1757:1758	MMP-9 EC 3.4.24.35	1751:1768	MMP-9 EC 3.4.24.35	1751:1768	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	4	57	from	sites	681:685	arg1	propeptide					700:709	the MMP-9 propeptide	690:709	the MMP-9 propeptide by MMP-3 and neutrophil elastase	690:742	First, we report new cleavage sites in the MMP-9 propeptide by MMP-3 and neutrophil elastase.
30422384	8	58	theme	healthy	1425:1431	arg1	controls					1433:1440	healthy controls	1425:1440	healthy controls	1425:1440	Additionally, proMMP-9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP-3.
30422384	4	59	theme	new	668:670	arg1	sites					681:685	new cleavage sites	668:685	new cleavage sites in the MMP-9 propeptide by MMP-3 and neutrophil elastase	668:742	First, we report new cleavage sites in the MMP-9 propeptide by MMP-3 and neutrophil elastase.
30422384	8	60	theme	Congenital	1366:1375	arg1	Disorder					1377:1384	Congenital Disorder	1366:1384	Congenital Disorder of Glycosylation patients	1366:1410	Additionally, proMMP-9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP-3.
30422384	3	61	theme	recombinant	613:623	arg1	pro-ATSf-9					638:647	recombinant glycosylated pro-ATSf-9	613:647	recombinant glycosylated pro-ATSf-9	613:647	We chemically synthesized aglycosyl pro-AT and pro-CT and purified recombinant glycosylated pro-ATSf-9 .
30422384	2	62	from	peptide	537:543	arg1	cleavage					452:459	cleavage	452:459	cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide	452:543	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	10	63	from	activity	1695:1702	arg1	pathology					1731:1739	pathology	1731:1739	pathology	1731:1739	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	10	63	from	activity	1695:1702	arg1	physiology					1716:1725	physiology	1716:1725	physiology	1716:1725	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	5	64	theme	protease-rich	947:959	arg1	fluids					970:975	protease-rich synovial fluids	947:975	protease-rich synovial fluids from rheumatoid arthritis patients	947:1010	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	6	65	theme	proteolytic	1070:1080	arg1	activation					1082:1091	proteolytic activation	1070:1091	proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis	1070:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	8	66	theme	patients	1403:1410	arg1	Disorder					1377:1384	Congenital Disorder	1366:1384	Congenital Disorder of Glycosylation patients	1366:1410	Additionally, proMMP-9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP-3.
30422384	0	67	theme	human	83:87	arg1	proMMP-9/progelatinase					89:110	human proMMP-9/progelatinase	83:110	human proMMP-9/progelatinase	83:110	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	6	68	theme	glycosylation	1053:1065	arg1	effect					1043:1048	the effect	1039:1048	the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis	1039:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	2	69	from	propeptide	468:477	arg1	peptide					537:543	an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide	482:543	peptide	537:543	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	2	69	from	propeptide	468:477	arg1	pro-AT					500:505	pro-AT	500:505	pro-AT	500:505	ProMMP-9 activation by MMP-3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro-AT) and carboxyterminal (pro-CT) peptide.
30422384	7	70	theme	proMMP-9	1276:1283	arg1	oligosaccharides					1239:1254	larger oligosaccharides	1232:1254	larger oligosaccharides of human neutrophil proMMP-9	1232:1283	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	0	71	theme	B.	112:113	arg1	metalloproteinases					122:139	B. Matrix metalloproteinases	112:139	B. Matrix metalloproteinases (MMPs)	112:146	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	0	71	theme	B.	112:113	arg1	proenzymes					164:173	proenzymes	164:173	proenzymes	164:173	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	0	71	theme	B.	112:113	arg1	MMPs					142:145	MMPs	142:145	MMPs	142:145	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	5	72	theme	neutrophil	920:929	arg1	MMP-3					896:900	MMP-3	896:900	MMP-3	896:900	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	5	72	theme	neutrophil	920:929	arg1	elastase					931:938	neutrophil elastase	920:938	neutrophil elastase	920:938	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	4	73	theme	neutrophil	724:733	arg1	elastase					735:742	neutrophil elastase	724:742	neutrophil elastase	724:742	First, we report new cleavage sites in the MMP-9 propeptide by MMP-3 and neutrophil elastase.
30422384	7	74	theme	neutrophil	1265:1274	arg1	proMMP-9					1276:1283	human neutrophil proMMP-9	1259:1283	human neutrophil proMMP-9	1259:1283	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	1	75	with	modification	357:368	arg1	oligosaccharide					387:401	an N-linked oligosaccharide	375:401	an N-linked oligosaccharide	375:401	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	10	76	from	mechanism	1654:1662	arg1	conclusion					1578:1587	conclusion	1578:1587	conclusion	1578:1587	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	11	77	theme	F	1879:1879	arg1	EC					1881:1882	PNGase F EC 3.5.1.52	1872:1891	PNGase F EC 3.5.1.52	1872:1891	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	77	theme	F	1879:1879	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	1	78	link	N-linked	378:385	arg1	oligosaccharide					387:401	an N-linked oligosaccharide	375:401	an N-linked oligosaccharide	375:401	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	5	79	theme	glycosylated	836:847	arg1	resistance					822:831	a higher resistance	813:831	a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis	813:891	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	8	80	theme	activation	1459:1468	arg1	rate					1470:1473	a higher activation rate	1450:1473	a higher activation rate by MMP-3	1450:1482	Additionally, proMMP-9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP-3.
30422384	0	81	theme	galectin-3	29:38	arg1	binding					40:46	galectin-3 binding	29:46	galectin-3 binding	29:46	Propeptide glycosylation and galectin-3 binding decrease proteolytic activation of human proMMP-9/progelatinase B. Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation.
30422384	5	82	theme	rheumatoid	982:991	arg1	arthritis					993:1001	rheumatoid arthritis	982:1001	rheumatoid arthritis patients	982:1010	Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro-AT against proteolysis by MMP-3, MMP-9, meprin α, neutrophil elastase and by protease-rich synovial fluids from rheumatoid arthritis patients.
30422384	6	83	theme	proMMP-9	1102:1109	arg1	activation					1082:1091	proteolytic activation	1070:1091	proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis	1070:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	10	84	theme	propeptide	1612:1621	arg1	glycosylation					1623:1635	MMP-9 propeptide glycosylation	1606:1635	MMP-9 propeptide glycosylation	1606:1635	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	7	85	theme	Sf-9	1206:1209	arg1	glycoforms					1220:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	1	86	theme	MMP	312:314	arg1	family					316:321	the MMP family	308:321	the MMP family	308:321	The MMP-9 propeptide is unique in the MMP family because of its post-translational modification with an N-linked oligosaccharide.
30422384	6	87	dep	zymography	1127:1136	arg1	analysis					1172:1179	cleavage analysis	1163:1179	cleavage analysis	1163:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	10	88	theme	fine-tuning	1642:1652	arg1	modification					1590:1601	modification	1590:1601	modification of MMP-9 propeptide glycosylation	1590:1635	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	10	88	theme	fine-tuning	1642:1652	arg1	mechanism					1654:1662	a fine-tuning mechanism	1640:1662	a fine-tuning mechanism	1640:1662	In conclusion, modification of MMP-9 propeptide glycosylation is a fine-tuning mechanism and co-determines the specific activity of MMP-9 in physiology and pathology.
30422384	6	89	with	activation	1082:1091	arg1	use					1120:1122	the use	1116:1122	the use of zymography and dye-quenched gelatin cleavage analysis	1116:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	11	90	theme	elastase	1825:1832	arg1	EC					1834:1835	neutrophil elastase EC 3.4.21.37	1814:1845	neutrophil elastase EC 3.4.21.37	1814:1845	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	90	theme	elastase	1825:1832	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	91	theme	MMP-9	1751:1755	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	91	theme	MMP-9	1751:1755	arg1	EC					1757:1758	MMP-9 EC 3.4.24.35	1751:1768	MMP-9 EC 3.4.24.35	1751:1768	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	6	92	theme	gelatin	1155:1161	arg1	use					1120:1122	the use	1116:1122	the use of zymography and dye-quenched gelatin cleavage analysis	1116:1179	Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP-9 with the use of zymography and dye-quenched gelatin cleavage analysis.
30422384	11	93	theme	MMP-3	1771:1775	arg1	EC					1777:1778	MMP-3 EC 3.4.24.17	1771:1788	MMP-3 EC 3.4.24.17	1771:1788	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	11	93	theme	MMP-3	1771:1775	arg1	ENZYMES					1742:1748	ENZYMES	1742:1748	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.	1742:1892	ENZYMES: MMP-9 EC 3.4.24.35, MMP-3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.
30422384	7	94	gly	glycoforms	1220:1229	arg1	Sf-9					1206:1209	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	7	94	gly	glycoforms	1220:1229	arg1	proMMP-9					1211:1218	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	recombinant Sf-9 proMMP-9 glycoforms	1194:1229	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30422384	7	95	theme	larger	1232:1237	arg1	oligosaccharides					1239:1254	larger oligosaccharides	1232:1254	larger oligosaccharides of human neutrophil proMMP-9	1232:1283	Compared to recombinant Sf-9 proMMP-9 glycoforms, larger oligosaccharides of human neutrophil proMMP-9 increased resistance against proteolytic activation.
30960012	7	0	theme	%	1209:1209	arg1	rates					1195:1199	iron release rates	1182:1199	iron release rates of 88⁻94% over 300 min	1182:1222	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	1	1	theme	cell	149:152	arg1	wall					154:157	the cell wall	145:157	the cell wall of leguminous plants	145:178	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	6	2	theme	antioxidant	984:994	arg1	activities					996:1005	antioxidant activities	984:1005	antioxidant activities for scavenging radicals	984:1029	Antioxidant assays indicated that both GM-40-Fe and GM-65-Fe exhibited antioxidant activities for scavenging radicals in vitro.
30960012	0	3	theme	Complex	75:81	arg1	Characterization					14:29	Characterization	14:29	Characterization	14:29	Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.
30960012	0	3	theme	Complex	75:81	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis	0:8	Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.
30960012	3	4	theme	activity	630:637	arg1	benefit					605:611	the added benefit	595:611	the added benefit of antioxidative activity	595:637	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	3	5	theme	galactomannan⁻iron	478:495	arg1	complexes					502:510	These galactomannan⁻iron(III) complexes	472:510	These galactomannan⁻iron(III) complexes	472:510	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	3	5	theme	galactomannan⁻iron	478:495	arg1	supplements					553:563	organic iron supplements	540:563	organic iron supplements	540:563	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	8	6	theme	iron	1412:1415	arg1	deficiency					1417:1426	iron deficiency	1412:1426	iron deficiency	1412:1426	These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.
30960012	4	7	theme	antioxidant	744:754	arg1	capacity					756:763	antioxidant capacity	744:763	antioxidant capacity	744:763	The prepared galactomannan⁻iron(III) complexes were characterized for chemical composition, morphology, antioxidant capacity, and bioavailability in vitro.
30960012	8	8	theme	iron	1378:1381	arg1	supplements					1383:1393	organic iron supplements	1370:1393	organic iron supplements to patients with iron deficiency	1370:1426	These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.
30960012	0	9	theme	Sesbania	88:95	arg1	Seed					97:100	Sesbania Seed	88:100	Sesbania Seed	88:100	Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.
30960012	5	10	theme	iron	877:880	arg1	contents					882:889	iron contents	877:889	iron contents	877:889	The results showed that galactomannan⁻iron(III) complexes could be produced with iron contents as high as 65.4 mg/g.
30960012	7	11	theme	release	1187:1193	arg1	rates					1195:1199	iron release rates	1182:1199	iron release rates of 88⁻94% over 300 min	1182:1222	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	4	12	theme	prepared	644:651	arg1	complexes					677:685	The prepared galactomannan⁻iron(III) complexes	640:685	The prepared galactomannan⁻iron(III) complexes	640:685	The prepared galactomannan⁻iron(III) complexes were characterized for chemical composition, morphology, antioxidant capacity, and bioavailability in vitro.
30960012	7	13	theme	intestinal	1150:1159	arg1	juices					1161:1166	artificial gastric and intestinal juices	1127:1166	artificial gastric and intestinal juices	1127:1166	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	6	14	theme	scavenging	1011:1020	arg1	radicals					1022:1029	scavenging radicals	1011:1029	scavenging radicals	1011:1029	Antioxidant assays indicated that both GM-40-Fe and GM-65-Fe exhibited antioxidant activities for scavenging radicals in vitro.
30960012	1	15	theme	leguminous	162:171	arg1	plants					173:178	leguminous plants	162:178	leguminous plants	162:178	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	1	16	from	polymer	134:140	arg1	wall					154:157	the cell wall	145:157	the cell wall of leguminous plants	145:178	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	8	17	theme	organic	1370:1376	arg1	supplements					1383:1393	organic iron supplements	1370:1393	organic iron supplements to patients with iron deficiency	1370:1426	These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.
30960012	1	18	theme	plants	173:178	arg1	wall					154:157	the cell wall	145:157	the cell wall of leguminous plants	145:178	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	7	19	theme	iron	1182:1185	arg1	rates					1195:1199	iron release rates	1182:1199	iron release rates of 88⁻94% over 300 min	1182:1222	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	3	20	theme	organic	540:546	arg1	supplements					553:563	organic iron supplements	540:563	organic iron supplements	540:563	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	3	20	theme	organic	540:546	arg1	complexes					502:510	These galactomannan⁻iron(III) complexes	472:510	These galactomannan⁻iron(III) complexes	472:510	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	7	21	theme	artificial	1127:1136	arg1	juices					1161:1166	artificial gastric and intestinal juices	1127:1166	artificial gastric and intestinal juices	1127:1166	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	2	22	theme	molecular	290:298	arg1	GM-65					319:323	GM-65	319:323	GM-65	319:323	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	22	theme	molecular	290:298	arg1	GM-40					309:313	GM-40	309:313	GM-40	309:313	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	22	theme	molecular	290:298	arg1	weights					300:306	different molecular weights	280:306	different molecular weights (GM-40 and GM-65)	280:324	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	8	23	theme	galactomannan⁻iron	1252:1269	arg1	complexes					1276:1284	galactomannan⁻iron(III) complexes	1252:1284	galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides	1252:1331	These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.
30960012	4	24	theme	chemical	710:717	arg1	composition					719:729	chemical composition	710:729	chemical composition	710:729	The prepared galactomannan⁻iron(III) complexes were characterized for chemical composition, morphology, antioxidant capacity, and bioavailability in vitro.
30960012	8	25	with	patients	1398:1405	arg1	deficiency					1417:1426	iron deficiency	1412:1426	iron deficiency	1412:1426	These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.
30960012	2	26	theme	different	280:288	arg1	GM-65					319:323	GM-65	319:323	GM-65	319:323	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	26	theme	different	280:288	arg1	GM-40					309:313	GM-40	309:313	GM-40	309:313	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	26	theme	different	280:288	arg1	weights					300:306	different molecular weights	280:306	different molecular weights (GM-40 and GM-65)	280:324	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	5	27	theme	galactomannan⁻iron	820:837	arg1	complexes					844:852	galactomannan⁻iron(III) complexes	820:852	galactomannan⁻iron(III) complexes	820:852	The results showed that galactomannan⁻iron(III) complexes could be produced with iron contents as high as 65.4 mg/g.
30960012	0	28	theme	Antioxidative	37:49	arg1	Complex					75:81	an Antioxidative Galactomannan⁻Iron(III) Complex	34:81	an Antioxidative Galactomannan⁻Iron(III) Complex	34:81	Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.
30960012	7	29	theme	iron	1045:1048	arg1	assays					1074:1079	The iron release/bioavailability assays	1041:1079	The iron release/bioavailability assays	1041:1079	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	3	30	theme	antioxidative	616:628	arg1	activity					630:637	antioxidative activity	616:637	antioxidative activity	616:637	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	7	31	theme	release/bioavailability	1050:1072	arg1	assays					1074:1079	The iron release/bioavailability assays	1041:1079	The iron release/bioavailability assays	1041:1079	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	3	32	theme	added	599:603	arg1	benefit					605:611	the added benefit	595:611	the added benefit of antioxidative activity	595:637	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	2	33	theme	galactomannan⁻iron	380:397	arg1	complexes					404:412	galactomannan⁻iron(III) complexes	380:412	galactomannan⁻iron(III) complexes	380:412	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	33	theme	galactomannan⁻iron	380:397	arg1	GM-40-Fe					435:442	GM-40-Fe	435:442	GM-40-Fe	435:442	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	33	theme	galactomannan⁻iron	380:397	arg1	GM-65-Fe					448:455	GM-65-Fe	448:455	GM-65-Fe	448:455	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	7	34	theme	gastric	1138:1144	arg1	juices					1161:1166	artificial gastric and intestinal juices	1127:1166	artificial gastric and intestinal juices	1127:1166	The iron release/bioavailability assays showed that the iron was easily released into artificial gastric and intestinal juices, resulting in iron release rates of 88⁻94% over 300 min.
30960012	6	35	theme	Antioxidant	913:923	arg1	assays					925:930	Antioxidant assays	913:930	Antioxidant assays	913:930	Antioxidant assays indicated that both GM-40-Fe and GM-65-Fe exhibited antioxidant activities for scavenging radicals in vitro.
30960012	3	36	theme	iron	548:551	arg1	supplements					553:563	organic iron supplements	540:563	organic iron supplements	540:563	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	3	36	theme	iron	548:551	arg1	complexes					502:510	These galactomannan⁻iron(III) complexes	472:510	These galactomannan⁻iron(III) complexes	472:510	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	8	37	theme	Sesbania	1303:1310	arg1	polysaccharides					1317:1331	Sesbania seed polysaccharides	1303:1331	Sesbania seed polysaccharides	1303:1331	These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.
30960012	0	38	theme	Galactomannan⁻Iron	51:68	arg1	Complex					75:81	an Antioxidative Galactomannan⁻Iron(III) Complex	34:81	an Antioxidative Galactomannan⁻Iron(III) Complex	34:81	Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.
30960012	1	39	contain	possess	200:206	arg1	polymer					134:140	a water-soluble polymer	118:140	a water-soluble polymer in the cell wall of leguminous plants	118:178	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	1	39	contain	possess	200:206	arg2	activity					237:244	anticancer and antioxidative activity	208:244	anticancer and antioxidative activity	208:244	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	1	39	contain	possess	200:206	arg1	Galactomannan					103:115	Galactomannan	103:115	Galactomannan	103:115	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	1	40	theme	water-soluble	120:132	arg1	polymer					134:140	a water-soluble polymer	118:140	a water-soluble polymer in the cell wall of leguminous plants	118:178	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	1	40	theme	water-soluble	120:132	arg1	Galactomannan					103:115	Galactomannan	103:115	Galactomannan	103:115	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	0	41	from	Seed	97:100	arg1	Characterization					14:29	Characterization	14:29	Characterization	14:29	Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.
30960012	0	41	from	Seed	97:100	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis	0:8	Synthesis and Characterization of an Antioxidative Galactomannan⁻Iron(III) Complex from Sesbania Seed.
30960012	8	42	theme	seed	1312:1315	arg1	polysaccharides					1317:1331	Sesbania seed polysaccharides	1303:1331	Sesbania seed polysaccharides	1303:1331	These results suggest that galactomannan⁻iron(III) complexes synthesized from Sesbania seed polysaccharides are capable of being administered as organic iron supplements to patients with iron deficiency.
30960012	2	43	dep	weights	300:306	arg1	GM-65					319:323	GM-65	319:323	GM-65	319:323	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	43	dep	weights	300:306	arg1	GM-40					309:313	GM-40	309:313	GM-40	309:313	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	43	dep	weights	300:306	arg1	weights					300:306	different molecular weights	280:306	different molecular weights (GM-40 and GM-65)	280:324	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	1	44	theme	anticancer	208:217	arg1	activity					237:244	anticancer and antioxidative activity	208:244	anticancer and antioxidative activity	208:244	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	3	45	theme	iron	574:577	arg1	deficiency					579:588	iron deficiency	574:588	iron deficiency	574:588	These galactomannan⁻iron(III) complexes are intended to function as organic iron supplements to treat iron deficiency with the added benefit of antioxidative activity.
30960012	2	46	theme	Sesbania	344:351	arg1	seeds					353:357	Sesbania seeds	344:357	Sesbania seeds	344:357	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	1	47	theme	antioxidative	223:235	arg1	activity					237:244	anticancer and antioxidative activity	208:244	anticancer and antioxidative activity	208:244	Galactomannan, a water-soluble polymer in the cell wall of leguminous plants, has been proven to possess anticancer and antioxidative activity.
30960012	4	48	theme	galactomannan⁻iron	653:670	arg1	complexes					677:685	The prepared galactomannan⁻iron(III) complexes	640:685	The prepared galactomannan⁻iron(III) complexes	640:685	The prepared galactomannan⁻iron(III) complexes were characterized for chemical composition, morphology, antioxidant capacity, and bioavailability in vitro.
30960012	2	49	with	galactomannan	261:273	arg1	GM-65					319:323	GM-65	319:323	GM-65	319:323	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	49	with	galactomannan	261:273	arg1	GM-40					309:313	GM-40	309:313	GM-40	309:313	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
30960012	2	49	with	galactomannan	261:273	arg1	weights					300:306	different molecular weights	280:306	different molecular weights (GM-40 and GM-65)	280:324	In this work, galactomannan with different molecular weights (GM-40 and GM-65) was obtained from Sesbania seeds and synthesized into galactomannan⁻iron(III) complexes, which are termed as GM-40-Fe and GM-65-Fe, respectively.
33525794	2	0	theme	diverse	518:524	arg1	glycoproteins					526:538	diverse glycoproteins	518:538	diverse glycoproteins	518:538	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	1	1	dep	expression	302:311	arg1	the					298:300	the	298:300	the	298:300	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	4	2	theme	recent	955:960	arg1	advances					962:969	recent advances	955:969	recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine	955:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	3	theme	pathway	915:921	arg1	performance					923:933	pathway performance	915:933	pathway performance	915:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	4	4	theme	engineering	1002:1012	arg1	tools					1014:1018	metabolic engineering tools	992:1018	metabolic engineering tools	992:1018	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	0	5	from	engineering	10:20	arg1	bacteria					54:61	bacteria	54:61	bacteria	54:61	Metabolic engineering of glycoprotein biosynthesis in bacteria.
33525794	4	6	from	advances	962:969	arg1	deployment					978:987	the deployment	974:987	the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine	974:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	7	theme	performance	923:933	arg1	identification					834:847	genome-wide identification	822:847	genome-wide identification of metabolic engineering targets	822:880	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	7	theme	performance	923:933	arg1	pathways					812:819	orthogonal glycosylation pathways	787:819	orthogonal glycosylation pathways	787:819	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	7	theme	performance	923:933	arg1	engineering					900:910	evolutionary engineering	887:910	evolutionary engineering of pathway performance	887:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	1	8	theme	using	272:276	arg1	bacteria					285:292	using simple bacteria	272:292	using simple bacteria	272:292	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	1	9	theme	simple	278:283	arg1	bacteria					285:292	using simple bacteria	272:292	using simple bacteria	272:292	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	2	10	theme	glycoconjugates	550:564	arg1	production					504:513	the production	500:513	the production of diverse glycoproteins and other glycoconjugates	500:564	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	0	11	from	bacteria	54:61	arg1	engineering					10:20	Metabolic engineering	0:20	Metabolic engineering of glycoprotein biosynthesis in bacteria	0:61	Metabolic engineering of glycoprotein biosynthesis in bacteria.
33525794	1	12	gly	glycoproteins	340:352	arg1	glycoproteins					340:352	complex glycoproteins	332:352	complex glycoproteins	332:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	3	13	theme	engineering	900:910	arg1	assembly					775:782	assembly	775:782	assembly	775:782	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	13	theme	engineering	900:910	arg1	design					764:769	rational design	755:769	rational design	755:769	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	2	14	theme	other	544:548	arg1	glycoconjugates					550:564	other glycoconjugates	544:564	other glycoconjugates	544:564	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	1	15	link	N-linked	186:193	arg1	machinery					217:225	the N-linked protein glycosylation machinery	182:225	the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins	182:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	4	16	with	targets	1123:1129	arg1	applications					1136:1147	applications	1136:1147	applications in research and medicine	1136:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	2	17	theme	microbial	465:473	arg1	glyco-factories					480:494	microbial cell glyco-factories	465:494	microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates	465:564	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	4	18	theme	cell	1056:1059	arg1	glyco-factories					1061:1075	microbial cell glyco-factories	1046:1075	microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine	1046:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	2	19	theme	cell	475:478	arg1	glyco-factories					480:494	microbial cell glyco-factories	465:494	microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates	465:564	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	0	20	from	biosynthesis	38:49	arg1	bacteria					54:61	bacteria	54:61	bacteria	54:61	Metabolic engineering of glycoprotein biosynthesis in bacteria.
33525794	4	21	from	applications	1136:1147	arg1	medicine					1165:1172	medicine	1165:1172	medicine	1165:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	4	21	from	applications	1136:1147	arg1	research					1152:1159	research	1152:1159	research	1152:1159	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	2	22	gly	glycoproteins	526:538	arg1	glycoproteins					526:538	diverse glycoproteins	518:538	diverse glycoproteins	518:538	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	3	23	theme	orthogonal	787:796	arg1	pathways					812:819	orthogonal glycosylation pathways	787:819	orthogonal glycosylation pathways	787:819	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	4	24	theme	microbial	1046:1054	arg1	glyco-factories					1061:1075	microbial cell glyco-factories	1046:1075	microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine	1046:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	0	25	theme	Metabolic	0:8	arg1	engineering					10:20	Metabolic engineering	0:20	Metabolic engineering of glycoprotein biosynthesis in bacteria	0:61	Metabolic engineering of glycoprotein biosynthesis in bacteria.
33525794	1	26	theme	N-linked	186:193	arg1	machinery					217:225	the N-linked protein glycosylation machinery	182:225	the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins	182:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	0	27	theme	glycoprotein	25:36	arg1	biosynthesis					38:49	glycoprotein biosynthesis	25:49	glycoprotein biosynthesis in bacteria	25:61	Metabolic engineering of glycoprotein biosynthesis in bacteria.
33525794	3	28	theme	genome-wide	822:832	arg1	identification					834:847	genome-wide identification	822:847	genome-wide identification of metabolic engineering targets	822:880	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	4	29	theme	tools	1014:1018	arg1	deployment					978:987	the deployment	974:987	the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine	974:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	30	theme	glycoprotein	631:642	arg1	platforms					655:663	efficient glycoprotein expression platforms	621:663	efficient glycoprotein expression platforms	621:663	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	31	theme	future	593:598	arg1	progress					600:607	future progress	593:607	future progress in creating efficient glycoprotein expression platforms in bacteria	593:675	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	1	32	theme	protein	195:201	arg1	machinery					217:225	the N-linked protein glycosylation machinery	182:225	the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins	182:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	3	33	theme	glycosylation	798:810	arg1	pathways					812:819	orthogonal glycosylation pathways	787:819	orthogonal glycosylation pathways	787:819	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	1	34	gly	glycoproteins	110:122	arg1	glycoproteins					110:122	glycoproteins	110:122	glycoproteins	110:122	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	1	35	dep	Escherichia	145:155	arg1	coli					157:160	coli	157:160	coli	157:160	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	1	36	theme	glycosylation	203:215	arg1	machinery					217:225	the N-linked protein glycosylation machinery	182:225	the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins	182:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	4	37	theme	high-value	1099:1108	arg1	targets					1123:1129	high-value glycoprotein targets	1099:1129	high-value glycoprotein targets with applications in research and medicine	1099:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	38	theme	pathways	812:819	arg1	assembly					775:782	assembly	775:782	assembly	775:782	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	38	theme	pathways	812:819	arg1	design					764:769	rational design	755:769	rational design	755:769	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	4	39	theme	strategies	1024:1033	arg1	deployment					978:987	the deployment	974:987	the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine	974:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	40	theme	expression	644:653	arg1	platforms					655:663	efficient glycoprotein expression platforms	621:663	efficient glycoprotein expression platforms	621:663	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	41	gly	glycoprotein	631:642	arg1	glycoprotein					631:642	efficient glycoprotein expression platforms	621:663	efficient glycoprotein expression platforms	621:663	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	0	42	theme	biosynthesis	38:49	arg1	engineering					10:20	Metabolic engineering	0:20	Metabolic engineering of glycoprotein biosynthesis in bacteria	0:61	Metabolic engineering of glycoprotein biosynthesis in bacteria.
33525794	3	43	theme	metabolic	852:860	arg1	targets					874:880	metabolic engineering targets	852:880	metabolic engineering targets	852:880	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	2	44	theme	important	421:429	arg1	role					431:434	an increasingly important role	405:434	an increasingly important role	405:434	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	4	45	theme	targets	1123:1129	arg1	production					1085:1094	the production	1081:1094	the production of high-value glycoprotein targets with applications in research and medicine	1081:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	46	theme	engineering	862:872	arg1	targets					874:880	metabolic engineering targets	852:880	metabolic engineering targets	852:880	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	47	theme	efficient	621:629	arg1	platforms					655:663	efficient glycoprotein expression platforms	621:663	efficient glycoprotein expression platforms	621:663	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	4	48	theme	glycoprotein	1110:1121	arg1	targets					1123:1129	high-value glycoprotein targets	1099:1129	high-value glycoprotein targets with applications in research and medicine	1099:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	49	theme	identification	834:847	arg1	assembly					775:782	assembly	775:782	assembly	775:782	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	49	theme	identification	834:847	arg1	design					764:769	rational design	755:769	rational design	755:769	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	50	theme	rational	755:762	arg1	design					764:769	rational design	755:769	rational design	755:769	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	51	theme	engineering	724:734	arg1	assembly					775:782	assembly	775:782	assembly	775:782	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	51	theme	engineering	724:734	arg1	design					764:769	rational design	755:769	rational design	755:769	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	51	theme	engineering	724:734	arg1	strategies					736:745	advanced strain engineering strategies	708:745	advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance	708:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	0	52	gly	glycoprotein	25:36	arg1	glycoprotein					25:36	glycoprotein biosynthesis	25:49	glycoprotein biosynthesis in bacteria	25:61	Metabolic engineering of glycoprotein biosynthesis in bacteria.
33525794	1	53	theme	complex	332:338	arg1	glycoproteins					340:352	complex glycoproteins	332:352	complex glycoproteins	332:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	4	54	theme	metabolic	992:1000	arg1	tools					1014:1018	metabolic engineering tools	992:1018	metabolic engineering tools	992:1018	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	55	theme	strategies	736:745	arg1	adoption					696:703	the adoption	692:703	the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance	692:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	1	56	theme	Campylobacter	232:244	arg1	jejuni					246:251	Campylobacter jejuni	232:251	Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins	232:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	1	57	from	jejuni	246:251	arg1	machinery					217:225	the N-linked protein glycosylation machinery	182:225	the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins	182:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	3	58	theme	advanced	708:715	arg1	assembly					775:782	assembly	775:782	assembly	775:782	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	58	theme	advanced	708:715	arg1	design					764:769	rational design	755:769	rational design	755:769	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	58	theme	advanced	708:715	arg1	strategies					736:745	advanced strain engineering strategies	708:745	advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance	708:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	2	59	theme	metabolic	372:380	arg1	engineering					382:392	metabolic engineering	372:392	metabolic engineering	372:392	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	3	60	theme	evolutionary	887:898	arg1	engineering					900:910	evolutionary engineering	887:910	evolutionary engineering of pathway performance	887:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	61	theme	strain	717:722	arg1	assembly					775:782	assembly	775:782	assembly	775:782	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	61	theme	strain	717:722	arg1	design					764:769	rational design	755:769	rational design	755:769	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	61	theme	strain	717:722	arg1	strategies					736:745	advanced strain engineering strategies	708:745	advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance	708:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	4	62	gly	glycoprotein	1110:1121	arg1	glycoprotein					1110:1121	high-value glycoprotein targets	1099:1129	high-value glycoprotein targets with applications in research and medicine	1099:1172	Here, we highlight recent advances in the deployment of metabolic engineering tools and strategies to develop microbial cell glyco-factories for the production of high-value glycoprotein targets with applications in research and medicine.
33525794	3	63	theme	targets	874:880	arg1	identification					834:847	genome-wide identification	822:847	genome-wide identification of metabolic engineering targets	822:880	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	63	theme	targets	874:880	arg1	pathways					812:819	orthogonal glycosylation pathways	787:819	orthogonal glycosylation pathways	787:819	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	3	63	theme	targets	874:880	arg1	engineering					900:910	evolutionary engineering	887:910	evolutionary engineering of pathway performance	887:933	It is becoming clear that future progress in creating efficient glycoprotein expression platforms in bacteria will depend on the adoption of advanced strain engineering strategies such as rational design and assembly of orthogonal glycosylation pathways, genome-wide identification of metabolic engineering targets, and evolutionary engineering of pathway performance.
33525794	2	64	theme	glycoproteins	526:538	arg1	production					504:513	the production	500:513	the production of diverse glycoproteins and other glycoconjugates	500:564	Since that time, metabolic engineering has played an increasingly important role in developing and optimizing microbial cell glyco-factories for the production of diverse glycoproteins and other glycoconjugates.
33525794	1	65	theme	glycoproteins	340:352	arg1	engineering					317:327	engineering	317:327	engineering	317:327	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	1	65	theme	glycoproteins	340:352	arg1	expression					302:311	expression	302:311	expression	302:311	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
33525794	1	66	theme	Escherichia	145:155	arg1	cells					162:166	Escherichia coli cells	145:166	Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins	145:352	The demonstration more than a decade ago that glycoproteins could be produced in Escherichia coli cells equipped with the N-linked protein glycosylation machinery from Campylobacter jejuni opened the door to using simple bacteria for the expression and engineering of complex glycoproteins.
30587575	0	0	theme	adhesion	95:102	arg1	complexes					104:112	focal adhesion complexes	89:112	focal adhesion complexes	89:112	O-GlcNAcylation regulates integrin-mediated cell adhesion and migration via formation of focal adhesion complexes.
30587575	10	1	theme	KD	1471:1472	arg1	cells					1474:1478	KD cells	1471:1478	KD cells	1471:1478	Consistently, levels of active integrin β1 were significantly enhanced in KD cells, whereas they were decreased in cells overexpressing OGT.
30587575	5	2	theme	O-GlcNAcylation	800:814	arg1	levels					782:787	The expression levels	767:787	The expression levels of OGT and O-GlcNAcylation	767:814	The expression levels of OGT and O-GlcNAcylation were remarkably suppressed 24 h after induction of doxycycline.
30587575	1	3	theme	serine	181:186	arg1	modification					155:166	a post-translational modification	134:166	a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm	134:276	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	1	3	theme	serine	181:186	arg1	O-GlcNAcylation					115:129	O-GlcNAcylation	115:129	O-GlcNAcylation	115:129	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	0	4	theme	focal	89:93	arg1	complexes					104:112	focal adhesion complexes	89:112	focal adhesion complexes	89:112	O-GlcNAcylation regulates integrin-mediated cell adhesion and migration via formation of focal adhesion complexes.
30587575	6	5	theme	OGT	893:895	arg1	Knockdown					880:888	Knockdown	880:888	Knockdown of OGT	880:895	Knockdown of OGT significantly promoted cell adhesion, but it suppressed the cell migration on fibronectin.
30587575	7	6	with	immunostaining	992:1005	arg1	marker					1024:1029	a marker	1022:1029	a marker for FA plaque	1022:1043	The immunostaining with paxillin, a marker for FA plaque, clearly showed that the number of FAs was increased in the KD cells compared with that in the control cells.
30587575	7	6	with	immunostaining	992:1005	arg1	paxillin					1012:1019	paxillin	1012:1019	paxillin	1012:1019	The immunostaining with paxillin, a marker for FA plaque, clearly showed that the number of FAs was increased in the KD cells compared with that in the control cells.
30587575	11	7	theme	novel	1557:1561	arg1	mechanism					1574:1582	a novel regulatory mechanism	1555:1582	a novel regulatory mechanism for O-GlcNAcylation	1555:1602	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	4	8	theme	FA	744:745	arg1	formation					756:764	focal adhesion (FA) complex formation	728:764	focal adhesion (FA) complex formation	728:764	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	9	theme	OGT	610:612	arg1	line					639:642	an OGT knockdown (KD) HeLa cell line	607:642	an OGT knockdown (KD) HeLa cell line	607:642	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	0	10	theme	complexes	104:112	arg1	formation					76:84	formation	76:84	formation of focal adhesion complexes	76:112	O-GlcNAcylation regulates integrin-mediated cell adhesion and migration via formation of focal adhesion complexes.
30587575	7	11	theme	FAs	1080:1082	arg1	number					1070:1075	the number	1066:1075	the number of FAs	1066:1082	The immunostaining with paxillin, a marker for FA plaque, clearly showed that the number of FAs was increased in the KD cells compared with that in the control cells.
30587575	9	12	theme	adhesion	1325:1332	arg1	kinase					1334:1339	focal adhesion kinase	1319:1339	focal adhesion kinase	1319:1339	Interestingly, the complex formation between integrin β1, focal adhesion kinase, paxillin, and talin was greatly increased in KD cells.
30587575	8	13	theme	focal	1206:1210	arg1	kinase					1221:1226	focal adhesion kinase	1206:1226	focal adhesion kinase	1206:1226	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase were down-regulated in KD cells.
30587575	11	14	theme	FA	1611:1612	arg1	formation					1622:1630	FA complex formation	1611:1630	FA complex formation	1611:1630	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	2	15	theme	important	301:309	arg1	roles					311:315	important roles	301:315	important roles	301:315	O-GlcNAcylation plays important roles in the cellular signaling that affect the different biological functions of cells, depending upon cell type.
30587575	1	16	theme	threonine	191:199	arg1	residue					201:207	a protein serine or threonine residue	171:207	residue	201:207	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	7	17	theme	control	1140:1146	arg1	cells					1148:1152	the control cells	1136:1152	the control cells	1136:1152	The immunostaining with paxillin, a marker for FA plaque, clearly showed that the number of FAs was increased in the KD cells compared with that in the control cells.
30587575	11	18	theme	integrin-mediated	1679:1695	arg1	functions					1697:1705	integrin-mediated functions	1679:1705	integrin-mediated functions such as cell adhesion and migration	1679:1741	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	11	18	theme	integrin-mediated	1679:1695	arg1	migration					1733:1741	migration	1733:1741	migration	1733:1741	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	11	18	theme	integrin-mediated	1679:1695	arg1	adhesion					1720:1727	cell adhesion	1715:1727	cell adhesion	1715:1727	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	6	19	from	migration	962:970	arg1	fibronectin					975:985	fibronectin	975:985	fibronectin	975:985	Knockdown of OGT significantly promoted cell adhesion, but it suppressed the cell migration on fibronectin.
30587575	1	20	theme	residue	201:207	arg1	modification					155:166	a post-translational modification	134:166	a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm	134:276	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	1	20	theme	residue	201:207	arg1	O-GlcNAcylation					115:129	O-GlcNAcylation	115:129	O-GlcNAcylation	115:129	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	4	21	used	used	530:533	arg2	we					527:528	we	527:528	we	527:528	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	6	22	theme	cell	957:960	arg1	migration					962:970	the cell migration	953:970	the cell migration on fibronectin	953:985	Knockdown of OGT significantly promoted cell adhesion, but it suppressed the cell migration on fibronectin.
30587575	8	23	theme	O-GlcNAcylation	1159:1173	arg1	levels					1175:1180	The O-GlcNAcylation levels	1155:1180	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase	1155:1226	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase were down-regulated in KD cells.
30587575	8	24	theme	talin	1195:1199	arg1	levels					1175:1180	The O-GlcNAcylation levels	1155:1180	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase	1155:1226	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase were down-regulated in KD cells.
30587575	0	25	theme	cell	44:47	arg1	adhesion					49:56	integrin-mediated cell adhesion	26:56	integrin-mediated cell adhesion	26:56	O-GlcNAcylation regulates integrin-mediated cell adhesion and migration via formation of focal adhesion complexes.
30587575	9	26	theme	complex	1280:1286	arg1	formation					1288:1296	the complex formation	1276:1296	the complex formation between integrin β1, focal adhesion kinase, paxillin, and talin	1276:1360	Interestingly, the complex formation between integrin β1, focal adhesion kinase, paxillin, and talin was greatly increased in KD cells.
30587575	10	27	theme	integrin	1428:1435	arg1	β1					1437:1438	active integrin β1	1421:1438	active integrin β1	1421:1438	Consistently, levels of active integrin β1 were significantly enhanced in KD cells, whereas they were decreased in cells overexpressing OGT.
30587575	11	28	theme	cell	1715:1718	arg1	adhesion					1720:1727	cell adhesion	1715:1727	cell adhesion	1715:1727	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	2	29	theme	cellular	324:331	arg1	signaling					333:341	the cellular signaling	320:341	the cellular signaling that affect the different biological functions of cells	320:397	O-GlcNAcylation plays important roles in the cellular signaling that affect the different biological functions of cells, depending upon cell type.
30587575	1	30	theme	O-GlcNAc	222:229	arg1	transferase					231:241	O-GlcNAc transferase	222:241	O-GlcNAc transferase (OGT) in the nucleus and cytoplasm	222:276	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	1	30	theme	O-GlcNAc	222:229	arg1	OGT					244:246	OGT	244:246	OGT	244:246	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	0	31	theme	integrin-mediated	26:42	arg1	adhesion					49:56	integrin-mediated cell adhesion	26:56	integrin-mediated cell adhesion	26:56	O-GlcNAcylation regulates integrin-mediated cell adhesion and migration via formation of focal adhesion complexes.
30587575	4	32	theme	complex	748:754	arg1	formation					756:764	focal adhesion (FA) complex formation	728:764	focal adhesion (FA) complex formation	728:764	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	33	theme	focal	728:732	arg1	formation					756:764	focal adhesion (FA) complex formation	728:764	focal adhesion (FA) complex formation	728:764	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	34	theme	HeLa	629:632	arg1	line					639:642	an OGT knockdown (KD) HeLa cell line	607:642	an OGT knockdown (KD) HeLa cell line	607:642	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	7	35	theme	KD	1105:1106	arg1	cells					1108:1112	the KD cells	1101:1112	the KD cells	1101:1112	The immunostaining with paxillin, a marker for FA plaque, clearly showed that the number of FAs was increased in the KD cells compared with that in the control cells.
30587575	2	36	theme	different	359:367	arg1	functions					380:388	the different biological functions	355:388	the different biological functions of cells	355:397	O-GlcNAcylation plays important roles in the cellular signaling that affect the different biological functions of cells, depending upon cell type.
30587575	7	37	theme	FA	1035:1036	arg1	plaque					1038:1043	FA plaque	1035:1043	FA plaque	1035:1043	The immunostaining with paxillin, a marker for FA plaque, clearly showed that the number of FAs was increased in the KD cells compared with that in the control cells.
30587575	8	38	theme	kinase	1221:1226	arg1	levels					1175:1180	The O-GlcNAcylation levels	1155:1180	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase	1155:1226	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase were down-regulated in KD cells.
30587575	9	39	theme	KD	1387:1388	arg1	cells					1390:1394	KD cells	1387:1394	KD cells	1387:1394	Interestingly, the complex formation between integrin β1, focal adhesion kinase, paxillin, and talin was greatly increased in KD cells.
30587575	3	40	theme	cell	476:479	arg1	adhesion					481:488	cell adhesion	476:488	cell adhesion	476:488	However, whether or not O-GlcNAcylation regulates cell adhesion and migration remains unclear.
30587575	8	41	theme	paxillin	1185:1192	arg1	levels					1175:1180	The O-GlcNAcylation levels	1155:1180	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase	1155:1226	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase were down-regulated in KD cells.
30587575	4	42	theme	short	561:565	arg1	shRNA					580:584	shRNA	580:584	shRNA	580:584	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	42	theme	short	561:565	arg1	RNA					575:577	the doxycycline-inducible short hairpin RNA	535:577	the doxycycline-inducible short hairpin RNA (shRNA) system	535:592	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	9	43	theme	focal	1319:1323	arg1	kinase					1334:1339	focal adhesion kinase	1319:1339	focal adhesion kinase	1319:1339	Interestingly, the complex formation between integrin β1, focal adhesion kinase, paxillin, and talin was greatly increased in KD cells.
30587575	4	44	theme	cell	698:701	arg1	adhesion					703:710	cell adhesion	698:710	cell adhesion	698:710	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	5	45	theme	OGT	792:794	arg1	levels					782:787	The expression levels	767:787	The expression levels of OGT and O-GlcNAcylation	767:814	The expression levels of OGT and O-GlcNAcylation were remarkably suppressed 24 h after induction of doxycycline.
30587575	6	46	theme	cell	920:923	arg1	adhesion					925:932	cell adhesion	920:932	cell adhesion	920:932	Knockdown of OGT significantly promoted cell adhesion, but it suppressed the cell migration on fibronectin.
30587575	4	47	theme	doxycycline-inducible	539:559	arg1	shRNA					580:584	shRNA	580:584	shRNA	580:584	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	47	theme	doxycycline-inducible	539:559	arg1	RNA					575:577	the doxycycline-inducible short hairpin RNA	535:577	the doxycycline-inducible short hairpin RNA (shRNA) system	535:592	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	2	48	theme	biological	369:378	arg1	functions					380:388	the different biological functions	355:388	the different biological functions of cells	355:397	O-GlcNAcylation plays important roles in the cellular signaling that affect the different biological functions of cells, depending upon cell type.
30587575	5	49	theme	expression	771:780	arg1	levels					782:787	The expression levels	767:787	The expression levels of OGT and O-GlcNAcylation	767:814	The expression levels of OGT and O-GlcNAcylation were remarkably suppressed 24 h after induction of doxycycline.
30587575	4	50	theme	RNA	575:577	arg1	system					587:592	the doxycycline-inducible short hairpin RNA (shRNA) system	535:592	the doxycycline-inducible short hairpin RNA (shRNA) system	535:592	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	11	51	theme	integrin	1655:1662	arg1	activation					1664:1673	integrin activation	1655:1673	integrin activation	1655:1673	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	5	52	dep	h	846:846	arg1	induction					854:862	induction	854:862	induction of doxycycline	854:877	The expression levels of OGT and O-GlcNAcylation were remarkably suppressed 24 h after induction of doxycycline.
30587575	1	53	theme	post-translational	136:153	arg1	modification					155:166	a post-translational modification	134:166	a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm	134:276	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	1	53	theme	post-translational	136:153	arg1	O-GlcNAcylation					115:129	O-GlcNAcylation	115:129	O-GlcNAcylation	115:129	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	4	54	theme	hairpin	567:573	arg1	shRNA					580:584	shRNA	580:584	shRNA	580:584	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	54	theme	hairpin	567:573	arg1	RNA					575:577	the doxycycline-inducible short hairpin RNA	535:577	the doxycycline-inducible short hairpin RNA (shRNA) system	535:592	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	11	55	theme	complex	1614:1620	arg1	formation					1622:1630	FA complex formation	1611:1630	FA complex formation	1611:1630	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	1	56	from	transferase	231:241	arg1	cytoplasm					268:276	cytoplasm	268:276	cytoplasm	268:276	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	1	56	from	transferase	231:241	arg1	nucleus					256:262	nucleus	256:262	nucleus	256:262	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	8	57	theme	KD	1251:1252	arg1	cells					1254:1258	KD cells	1251:1258	KD cells	1251:1258	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase were down-regulated in KD cells.
30587575	4	58	theme	adhesion	734:741	arg1	formation					756:764	focal adhesion (FA) complex formation	728:764	focal adhesion (FA) complex formation	728:764	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	8	59	theme	adhesion	1212:1219	arg1	kinase					1221:1226	focal adhesion kinase	1206:1226	focal adhesion kinase	1206:1226	The O-GlcNAcylation levels of paxillin, talin, and focal adhesion kinase were down-regulated in KD cells.
30587575	10	60	theme	β1	1437:1438	arg1	levels					1411:1416	levels	1411:1416	levels of active integrin β1	1411:1438	Consistently, levels of active integrin β1 were significantly enhanced in KD cells, whereas they were decreased in cells overexpressing OGT.
30587575	1	61	theme	protein	173:179	arg1	serine					181:186	a protein serine or threonine residue	171:207	serine	181:186	O-GlcNAcylation is a post-translational modification of a protein serine or threonine residue catalyzed by O-GlcNAc transferase (OGT) in the nucleus and cytoplasm.
30587575	4	62	theme	knockdown	614:622	arg1	line					639:642	an OGT knockdown (KD) HeLa cell line	607:642	an OGT knockdown (KD) HeLa cell line	607:642	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	10	63	theme	active	1421:1426	arg1	β1					1437:1438	active integrin β1	1421:1438	active integrin β1	1421:1438	Consistently, levels of active integrin β1 were significantly enhanced in KD cells, whereas they were decreased in cells overexpressing OGT.
30587575	5	64	theme	doxycycline	867:877	arg1	induction					854:862	induction	854:862	induction of doxycycline	854:877	The expression levels of OGT and O-GlcNAcylation were remarkably suppressed 24 h after induction of doxycycline.
30587575	4	65	theme	cell	634:637	arg1	line					639:642	an OGT knockdown (KD) HeLa cell line	607:642	an OGT knockdown (KD) HeLa cell line	607:642	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	66	theme	key	680:682	arg1	regulator					684:692	a key regulator	678:692	a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation	678:764	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	4	66	theme	key	680:682	arg1	O-GlcNAcylation					659:673	O-GlcNAcylation	659:673	O-GlcNAcylation	659:673	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
30587575	2	67	theme	cell	415:418	arg1	type					420:423	cell type	415:423	cell type	415:423	O-GlcNAcylation plays important roles in the cellular signaling that affect the different biological functions of cells, depending upon cell type.
30587575	11	68	theme	regulatory	1563:1572	arg1	mechanism					1574:1582	a novel regulatory mechanism	1555:1582	a novel regulatory mechanism for O-GlcNAcylation	1555:1602	The data suggest a novel regulatory mechanism for O-GlcNAcylation during FA complex formation, which thereby affects integrin activation and integrin-mediated functions such as cell adhesion and migration.
30587575	7	69	dep	increased	1088:1096	arg1	compared					1114:1121	compared	1114:1121	compared with that in the control cells	1114:1152	The immunostaining with paxillin, a marker for FA plaque, clearly showed that the number of FAs was increased in the KD cells compared with that in the control cells.
30587575	2	70	theme	cells	393:397	arg1	functions					380:388	the different biological functions	355:388	the different biological functions of cells	355:397	O-GlcNAcylation plays important roles in the cellular signaling that affect the different biological functions of cells, depending upon cell type.
30587575	4	71	theme	KD	625:626	arg1	line					639:642	an OGT knockdown (KD) HeLa cell line	607:642	an OGT knockdown (KD) HeLa cell line	607:642	Here, we used the doxycycline-inducible short hairpin RNA (shRNA) system to establish an OGT knockdown (KD) HeLa cell line and found that O-GlcNAcylation is a key regulator for cell adhesion, migration, and focal adhesion (FA) complex formation.
31041386	11	0	theme	acid	1621:1624	arg1	modifications					1626:1638	nucleic acid modifications	1613:1638	nucleic acid modifications	1613:1638	We envision these general methods will be applicable to diverse protein and nucleic acid modifications.
31041386	10	1	theme	normalization	1434:1446	arg1	strategies					1448:1457	new normalization strategies	1430:1457	new normalization strategies	1430:1457	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	5	2	theme	time-dependent	584:597	arg1	turnover					599:606	monitoring time-dependent turnover	573:606	monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin	573:662	Here we use DNA precipitation methods to enable monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin.
31041386	1	3	theme	experimental	161:172	arg1	modalities					174:183	new experimental modalities	157:183	new experimental modalities for studying chromatin	157:206	Advances in DNA sequencing are enabling new experimental modalities for studying chromatin.
31041386	7	4	theme	sequencing	976:985	arg1	data					987:990	resulting next-generation DNA sequencing data	946:990	resulting next-generation DNA sequencing data	946:990	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	0	5	theme	Turnover	74:81	arg1	Dynamics					53:60	Genome-Wide Dynamics	41:60	Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins	41:114	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.
31041386	4	6	theme	gene	484:487	arg1	transcription					489:501	gene transcription	484:501	gene transcription	484:501	The mechanisms by which O-GlcNAc regulates gene transcription are of high interest.
31041386	10	7	from	turnover	1332:1339	arg1	chromatin					1356:1364	chromatin	1356:1364	chromatin	1356:1364	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	10	8	theme	chemical	1511:1518	arg1	methods					1528:1534	chemical genetic methods	1511:1534	chemical genetic methods	1511:1534	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	6	9	theme	reporter	697:704	arg1	strategy					706:713	an antibody-free chemical reporter strategy	671:713	an antibody-free chemical reporter strategy to map O-GlcNAc to the genome	671:743	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	8	10	theme	OGA	1126:1128	arg1	loss					1118:1121	loss	1118:1121	loss of OGA	1118:1128	Notably, loss of OGA only increases this half-life by ∼3-fold.
31041386	9	11	theme	OGA	1253:1255	arg1	loss					1245:1248	loss	1245:1248	loss of OGA	1245:1255	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	6	12	theme	chemical	688:695	arg1	strategy					706:713	an antibody-free chemical reporter strategy	671:713	an antibody-free chemical reporter strategy to map O-GlcNAc to the genome	671:743	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	0	13	theme	Chromatin-Associated	86:105	arg1	Proteins					107:114	Chromatin-Associated Proteins	86:114	Chromatin-Associated Proteins	86:114	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.
31041386	0	14	from	Dynamics	53:60	arg1	Proteins					107:114	Chromatin-Associated Proteins	86:114	Chromatin-Associated Proteins	86:114	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.
31041386	10	15	theme	blinding	1400:1407	arg1	analyses					1496:1503	coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses	1394:1503	coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods	1394:1534	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	7	16	theme	most	1051:1054	arg1	loci					1064:1067	most genomic loci	1051:1067	most genomic loci	1051:1067	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	7	17	from	loci	1064:1067	arg1	O-GlcNAc					1006:1013	O-GlcNAc	1006:1013	O-GlcNAc on chromatin-associated proteins at most genomic loci	1006:1067	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	6	18	theme	feeding	781:787	arg1	experiments					789:799	time course metabolic feeding experiments	759:799	time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc	759:931	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	10	19	theme	O-GlcNAc	1344:1351	arg1	turnover					1332:1339	monitoring turnover	1321:1339	monitoring turnover of O-GlcNAc on chromatin	1321:1364	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	3	20	theme	reversible	364:373	arg1	N-acetylglucosamine					328:346	O-Linked N-acetylglucosamine	319:346	O-Linked N-acetylglucosamine (O-GlcNAc)	319:357	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	3	20	theme	reversible	364:373	arg1	modification					383:394	a reversible protein modification	362:394	a reversible protein modification found on many chromatin-associated proteins	362:438	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	7	21	theme	genomic	1056:1062	arg1	loci					1064:1067	most genomic loci	1051:1067	most genomic loci	1051:1067	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	5	22	theme	DNA	537:539	arg1	methods					555:561	DNA precipitation methods	537:561	DNA precipitation methods	537:561	Here we use DNA precipitation methods to enable monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin.
31041386	3	23	theme	protein	375:381	arg1	N-acetylglucosamine					328:346	O-Linked N-acetylglucosamine	319:346	O-Linked N-acetylglucosamine (O-GlcNAc)	319:357	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	3	23	theme	protein	375:381	arg1	modification					383:394	a reversible protein modification	362:394	a reversible protein modification found on many chromatin-associated proteins	362:438	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	10	24	theme	coded	1394:1398	arg1	analyses					1496:1503	coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses	1394:1503	coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods	1394:1534	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	5	25	theme	proteins	629:636	arg1	turnover					599:606	monitoring time-dependent turnover	573:606	monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin	573:662	Here we use DNA precipitation methods to enable monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin.
31041386	5	26	theme	precipitation	541:553	arg1	methods					555:561	DNA precipitation methods	537:561	DNA precipitation methods	537:561	Here we use DNA precipitation methods to enable monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin.
31041386	0	27	theme	Chemical	2:9	arg1	Method					19:24	A Chemical Genetic Method	0:24	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.	0:115	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.
31041386	10	28	theme	samples	1412:1418	arg1	blinding					1400:1407	blinding	1400:1407	blinding	1400:1407	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	6	29	theme	time	759:762	arg1	course					764:769	time course	759:769	time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc	759:931	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	10	30	theme	new	1430:1432	arg1	strategies					1448:1457	new normalization strategies	1430:1457	new normalization strategies	1430:1457	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	11	31	theme	nucleic	1613:1619	arg1	modifications					1626:1638	nucleic acid modifications	1613:1638	nucleic acid modifications	1613:1638	We envision these general methods will be applicable to diverse protein and nucleic acid modifications.
31041386	7	32	from	half-life	1089:1097	arg1	hours					1102:1106	hours	1102:1106	hours	1102:1106	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	10	33	theme	genetic	1520:1526	arg1	methods					1528:1534	chemical genetic methods	1511:1534	chemical genetic methods	1511:1534	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	6	34	theme	O-GlcNAc	859:866	arg1	OGA					879:881	OGA	879:881	OGA	879:881	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	6	34	theme	O-GlcNAc	859:866	arg1	hydrolase					868:876	O-GlcNAc hydrolase	859:876	O-GlcNAc hydrolase (OGA)	859:882	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	11	35	theme	general	1555:1561	arg1	methods					1563:1569	these general methods	1549:1569	these general methods	1549:1569	We envision these general methods will be applicable to diverse protein and nucleic acid modifications.
31041386	3	36	theme	many	405:408	arg1	proteins					431:438	many chromatin-associated proteins	405:438	many chromatin-associated proteins	405:438	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	9	37	theme	loci	1210:1213	arg1	loci					1210:1213	genomic loci	1202:1213	genomic loci	1202:1213	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	9	37	theme	loci	1210:1213	arg1	sensitive					1232:1240	sensitive	1232:1240	sensitive	1232:1240	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	9	37	theme	loci	1210:1213	arg1	set					1195:1197	a small set	1187:1197	a small set of genomic loci	1187:1213	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	7	38	from	O-GlcNAc	1006:1013	arg1	proteins					1039:1046	chromatin-associated proteins	1018:1046	chromatin-associated proteins	1018:1046	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	9	39	theme	small	1189:1193	arg1	loci					1210:1213	genomic loci	1202:1213	genomic loci	1202:1213	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	9	39	theme	small	1189:1193	arg1	sensitive					1232:1240	sensitive	1232:1240	sensitive	1232:1240	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	9	39	theme	small	1189:1193	arg1	set					1195:1197	a small set	1187:1197	a small set of genomic loci	1187:1213	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	6	40	theme	metabolic	771:779	arg1	experiments					789:799	time course metabolic feeding experiments	759:799	time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc	759:931	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	10	41	theme	new	1296:1298	arg1	strategies					1300:1309	new strategies	1296:1309	new strategies to permit monitoring turnover of O-GlcNAc on chromatin	1296:1364	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	7	42	theme	resulting	946:954	arg1	data					987:990	resulting next-generation DNA sequencing data	946:990	resulting next-generation DNA sequencing data	946:990	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	2	43	theme	DNA	253:255	arg1	sequencing					257:266	high-throughput DNA sequencing	237:266	high-throughput DNA sequencing	237:266	One emerging area is to use high-throughput DNA sequencing to monitor dynamic changes occurring to chromatin.
31041386	10	44	dep	blinding	1400:1407	arg1	genome-wide					1484:1494	genome-wide	1484:1494	genome-wide	1484:1494	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	4	45	theme	high	510:513	arg1	interest					515:522	high interest	510:522	high interest	510:522	The mechanisms by which O-GlcNAc regulates gene transcription are of high interest.
31041386	2	46	theme	high-throughput	237:251	arg1	sequencing					257:266	high-throughput DNA sequencing	237:266	high-throughput DNA sequencing	237:266	One emerging area is to use high-throughput DNA sequencing to monitor dynamic changes occurring to chromatin.
31041386	9	47	theme	genomic	1202:1208	arg1	loci					1210:1213	genomic loci	1202:1213	genomic loci	1202:1213	Interestingly, a small set of genomic loci are particularly sensitive to loss of OGA.
31041386	0	48	theme	Genome-Wide	41:51	arg1	Dynamics					53:60	Genome-Wide Dynamics	41:60	Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins	41:114	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.
31041386	5	49	theme	O-GlcNAc	611:618	arg1	proteins					629:636	O-GlcNAc modified proteins	611:636	O-GlcNAc modified proteins associated with chromatin	611:662	Here we use DNA precipitation methods to enable monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin.
31041386	1	50	theme	DNA	129:131	arg1	sequencing					133:142	DNA sequencing	129:142	DNA sequencing	129:142	Advances in DNA sequencing are enabling new experimental modalities for studying chromatin.
31041386	7	51	theme	chromatin-associated	1018:1037	arg1	proteins					1039:1046	chromatin-associated proteins	1018:1046	chromatin-associated proteins	1018:1046	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	2	52	theme	dynamic	279:285	arg1	changes					287:293	dynamic changes	279:293	dynamic changes occurring to chromatin	279:316	One emerging area is to use high-throughput DNA sequencing to monitor dynamic changes occurring to chromatin.
31041386	5	53	theme	modified	620:627	arg1	proteins					629:636	O-GlcNAc modified proteins	611:636	O-GlcNAc modified proteins associated with chromatin	611:662	Here we use DNA precipitation methods to enable monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin.
31041386	1	54	from	Advances	117:124	arg1	sequencing					133:142	DNA sequencing	129:142	DNA sequencing	129:142	Advances in DNA sequencing are enabling new experimental modalities for studying chromatin.
31041386	10	55	theme	monitoring	1321:1330	arg1	turnover					1332:1339	monitoring turnover	1321:1339	monitoring turnover of O-GlcNAc on chromatin	1321:1364	In addition to these observations and new strategies to permit monitoring turnover of O-GlcNAc on chromatin, we also detail methods for coded blinding of samples alongside new normalization strategies to enable time-resolved, genome-wide analyses using chemical genetic methods.
31041386	3	56	theme	O-Linked	319:326	arg1	modification					383:394	a reversible protein modification	362:394	a reversible protein modification found on many chromatin-associated proteins	362:438	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	3	56	theme	O-Linked	319:326	arg1	O-GlcNAc					349:356	O-GlcNAc	349:356	O-GlcNAc	349:356	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	3	56	theme	O-Linked	319:326	arg1	N-acetylglucosamine					328:346	O-Linked N-acetylglucosamine	319:346	O-Linked N-acetylglucosamine (O-GlcNAc)	319:357	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	2	57	theme	emerging	213:220	arg1	area					222:225	One emerging area	209:225	One emerging area	209:225	One emerging area is to use high-throughput DNA sequencing to monitor dynamic changes occurring to chromatin.
31041386	6	58	theme	Drosophila	816:825	arg1	larvae					827:832	wild-type Drosophila larvae	806:832	wild-type Drosophila larvae	806:832	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	1	59	theme	new	157:159	arg1	modalities					174:183	new experimental modalities	157:183	new experimental modalities for studying chromatin	157:206	Advances in DNA sequencing are enabling new experimental modalities for studying chromatin.
31041386	7	60	theme	data	987:990	arg1	Analysis					934:941	Analysis	934:941	Analysis of resulting next-generation DNA sequencing data	934:990	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	6	61	theme	course	764:769	arg1	experiments					789:799	time course metabolic feeding experiments	759:799	time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc	759:931	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	0	62	theme	O-GlcNAc	65:72	arg1	Turnover					74:81	O-GlcNAc Turnover	65:81	O-GlcNAc Turnover	65:81	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.
31041386	7	63	theme	next-generation	956:970	arg1	data					987:990	resulting next-generation DNA sequencing data	946:990	resulting next-generation DNA sequencing data	946:990	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	11	64	theme	diverse	1593:1599	arg1	protein					1601:1607	diverse protein	1593:1607	diverse protein	1593:1607	We envision these general methods will be applicable to diverse protein and nucleic acid modifications.
31041386	6	65	theme	wild-type	806:814	arg1	larvae					827:832	wild-type Drosophila larvae	806:832	wild-type Drosophila larvae	806:832	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	6	66	theme	antibody-free	674:686	arg1	strategy					706:713	an antibody-free chemical reporter strategy	671:713	an antibody-free chemical reporter strategy to map O-GlcNAc to the genome	671:743	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
31041386	3	67	located	found	396:400	arg1	proteins					431:438	many chromatin-associated proteins	405:438	many chromatin-associated proteins	405:438	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	3	67	located	found	396:400	arg2	N-acetylglucosamine					328:346	O-Linked N-acetylglucosamine	319:346	O-Linked N-acetylglucosamine (O-GlcNAc)	319:357	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	3	67	located	found	396:400	arg2	modification					383:394	a reversible protein modification	362:394	a reversible protein modification found on many chromatin-associated proteins	362:438	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	0	68	theme	Genetic	11:17	arg1	Method					19:24	A Chemical Genetic Method	0:24	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.	0:115	A Chemical Genetic Method for Monitoring Genome-Wide Dynamics of O-GlcNAc Turnover on Chromatin-Associated Proteins.
31041386	5	69	theme	monitoring	573:582	arg1	turnover					599:606	monitoring time-dependent turnover	573:606	monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin	573:662	Here we use DNA precipitation methods to enable monitoring time-dependent turnover of O-GlcNAc modified proteins associated with chromatin.
31041386	3	70	theme	chromatin-associated	410:429	arg1	proteins					431:438	many chromatin-associated proteins	405:438	many chromatin-associated proteins	405:438	O-Linked N-acetylglucosamine (O-GlcNAc) is a reversible protein modification found on many chromatin-associated proteins.
31041386	7	71	theme	DNA	972:974	arg1	data					987:990	resulting next-generation DNA sequencing data	946:990	resulting next-generation DNA sequencing data	946:990	Analysis of resulting next-generation DNA sequencing data revealed that O-GlcNAc on chromatin-associated proteins at most genomic loci is processed with a half-life in hours.
31041386	6	72	with	experiments	789:799	arg1	larvae					827:832	wild-type Drosophila larvae	806:832	wild-type Drosophila larvae	806:832	Using an antibody-free chemical reporter strategy to map O-GlcNAc to the genome, we performed time course metabolic feeding experiments with wild-type Drosophila larvae alongside larvae lacking O-GlcNAc hydrolase (OGA), which are accordingly unable to remove O-GlcNAc.
29606577	1	0	link	O-linked	88:95	arg1	OGT					146:148	OGT	146:148	OGT	146:148	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	0	link	O-linked	88:95	arg1	transferase					133:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	88:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	88:149	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	3	1	theme	tetratricopeptide	522:538	arg1	repeats					540:546	the tetratricopeptide repeats	518:546	the tetratricopeptide repeats	518:546	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	3	2	theme	repeats	540:546	arg1	activity					560:567	reduced activity	552:567	reduced activity	552:567	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	3	2	theme	repeats	540:546	arg1	changes					507:513	conformational changes	492:513	conformational changes of the tetratricopeptide repeats	492:546	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	2	3	theme	intellectual	312:323	arg1	disability					325:334	intellectual disability	312:334	intellectual disability	312:334	Recently, OGT mutations have been associated with intellectual disability, although it is not understood how they affect OGT structure and function.
29606577	1	4	theme	protein	161:167	arg1	abundant					239:246	abundant	239:246	abundant	239:246	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	4	theme	protein	161:167	arg1	modification					218:229	an essential post-translational modification	186:229	an essential post-translational modification that is abundant in the brain	186:259	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	4	theme	protein	161:167	arg1	O-GlcNAcylation					169:183	protein O-GlcNAcylation	161:183	protein O-GlcNAcylation	161:183	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	3	5	theme	multi-disciplinary	419:436	arg1	approach					438:445	a multi-disciplinary approach	417:445	a multi-disciplinary approach	417:445	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	0	6	theme	O-GlcNAc	4:11	arg1	Transferase					13:23	The O-GlcNAc Transferase	0:23	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.
29606577	1	7	theme	O-linked	88:95	arg1	OGT					146:148	OGT	146:148	OGT	146:148	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	7	theme	O-linked	88:95	arg1	transferase					133:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	88:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	88:149	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	8	theme	essential	189:197	arg1	O-GlcNAcylation					169:183	protein O-GlcNAcylation	161:183	protein O-GlcNAcylation	161:183	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	8	theme	essential	189:197	arg1	modification					218:229	an essential post-translational modification	186:229	an essential post-translational modification that is abundant in the brain	186:259	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	8	theme	essential	189:197	arg1	abundant					239:246	abundant	239:246	abundant	239:246	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	9	theme	β-N-acetyl-D-glucosamine	97:120	arg1	OGT					146:148	OGT	146:148	OGT	146:148	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	9	theme	β-N-acetyl-D-glucosamine	97:120	arg1	transferase					133:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	88:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	88:149	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	10	theme	post-translational	199:216	arg1	O-GlcNAcylation					169:183	protein O-GlcNAcylation	161:183	protein O-GlcNAcylation	161:183	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	10	theme	post-translational	199:216	arg1	modification					218:229	an essential post-translational modification	186:229	an essential post-translational modification that is abundant in the brain	186:259	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	10	theme	post-translational	199:216	arg1	abundant					239:246	abundant	239:246	abundant	239:246	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	0	11	theme	Intellectual	25:36	arg1	L254F					58:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.
29606577	3	12	theme	molecular	584:592	arg1	mechanisms					594:603	the molecular mechanisms	580:603	the molecular mechanisms contributing to pathogenesis	580:632	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	0	13	theme	Transferase	13:23	arg1	L254F					58:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.
29606577	1	14	theme	O-GlcNAc	123:130	arg1	OGT					146:148	OGT	146:148	OGT	146:148	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	14	theme	O-GlcNAc	123:130	arg1	transferase					133:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	88:143	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	88:149	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	0	15	theme	Mutation	49:56	arg1	L254F					58:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.
29606577	3	16	theme	L254F	464:468	arg1	OGT mutation					470:481	the L254F OGT mutation	460:481	the L254F OGT mutation	460:481	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	0	17	theme	Disability	38:47	arg1	L254F					58:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F	0:62	The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.
29606577	3	18	dep	show	450:453	arg1	Using					411:415	Using	411:415	Using a multi-disciplinary approach	411:445	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	1	19	from	brain	255:259	arg1	O-GlcNAcylation					169:183	protein O-GlcNAcylation	161:183	protein O-GlcNAcylation	161:183	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	19	from	brain	255:259	arg1	modification					218:229	an essential post-translational modification	186:229	an essential post-translational modification that is abundant in the brain	186:259	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	19	from	brain	255:259	arg1	abundant					239:246	abundant	239:246	abundant	239:246	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	1	20	from	abundant	239:246	arg1	brain					255:259	the brain	251:259	the brain	251:259	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain.
29606577	3	21	theme	conformational	492:505	arg1	changes					507:513	conformational changes	492:513	conformational changes of the tetratricopeptide repeats	492:546	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
29606577	2	22	theme	OGT	272:274	arg1	mutations					276:284	OGT mutations	272:284	OGT mutations	272:284	Recently, OGT mutations have been associated with intellectual disability, although it is not understood how they affect OGT structure and function.
29606577	0	23	theme	TPR	77:79	arg1	Helix					81:85	the TPR Helix	73:85	the TPR Helix	73:85	The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.
29606577	2	24	theme	OGT	383:385	arg1	structure					387:395	OGT structure	383:395	OGT structure	383:395	Recently, OGT mutations have been associated with intellectual disability, although it is not understood how they affect OGT structure and function.
29606577	3	25	theme	reduced	552:558	arg1	activity					560:567	reduced activity	552:567	reduced activity	552:567	Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis.
31233798	0	0	theme	cyanobacterium	91:104	arg1	mutant					126:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	5	1	theme	groups	821:826	arg1	presence					790:797	the presence	786:797	the presence of several functional groups	786:826	FTIR analysis confirmed the presence of several functional groups.
31233798	4	2	theme	aqueous	743:749	arg1	solutions					751:759	highly concentrated aqueous solutions	723:759	highly concentrated aqueous solutions	723:759	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	6	3	theme	ovary	950:954	arg1	cells					966:970	ovary carcinoma cells	950:970	ovary carcinoma cells	950:970	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	6	4	theme	cells	966:970	arg1	viability					915:923	the viability	911:923	the viability of melanoma, thyroid and ovary carcinoma cells	911:970	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	7	5	theme	s	1187:1187	arg1	production					1134:1143	the sustainable production	1118:1143	the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1118:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	6	6	theme	strong	872:877	arg1	activity					890:897	strong biological activity	872:897	strong biological activity	872:897	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	4	7	theme	concentrated	730:741	arg1	solutions					751:759	highly concentrated aqueous solutions	723:759	highly concentrated aqueous solutions	723:759	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	0	8	theme	ΔsigF	120:124	arg1	mutant					126:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	0	9	from	Characterization	0:15	arg1	mutant					126:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	7	10	theme	carbohydrate	1166:1177	arg1	s					1187:1187	biological active carbohydrate polymer(s)	1148:1188	biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1148:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	4	11	theme	molecular	642:650	arg1	mass					652:655	high molecular mass	637:655	high molecular mass fractions	637:665	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	0	12	theme	Synechocystis	106:118	arg1	mutant					126:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	4	13	theme	amorphous	530:538	arg1	polymer					540:546	This amorphous polymer	525:546	This amorphous polymer	525:546	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	6	14	theme	caspase-3	1026:1034	arg1	activation					1036:1045	p53 and caspase-3 activation	1018:1045	activation	1036:1045	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	6	15	contain	has	868:870	arg1	polymer					860:866	the ΔsigF polymer	850:866	the ΔsigF polymer	850:866	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	6	15	contain	has	868:870	arg2	activity					890:897	strong biological activity	872:897	strong biological activity	872:897	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	4	16	theme	high	637:640	arg1	mass					652:655	high molecular mass	637:655	high molecular mass fractions	637:665	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	7	17	theme	biological	1148:1157	arg1	s					1187:1187	biological active carbohydrate polymer(s)	1148:1188	biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1148:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	6	18	theme	ΔsigF	854:858	arg1	polymer					860:866	the ΔsigF polymer	850:866	the ΔsigF polymer	850:866	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	1	19	theme	biotechnological	217:232	arg1	applications					234:245	biotechnological applications	217:245	biotechnological applications	217:245	Cyanobacterial extracellular carbohydrate polymers are particularly attractive for biotechnological applications.
31233798	0	20	theme	extracellular	47:59	arg1	polymer					74:80	the extracellular carbohydrate polymer	43:80	the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant	43:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	6	21	theme	thyroid	938:944	arg1	viability					915:923	the viability	911:923	the viability of melanoma, thyroid and ovary carcinoma cells	911:970	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	6	22	theme	p53	1018:1020	arg1	activation					1036:1045	p53 and caspase-3 activation	1018:1045	activation	1036:1045	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	2	23	theme	ΔsigF	340:344	arg1	composition					294:304	the monosaccharidic composition	274:304	the monosaccharidic composition of the polymer of a Synechocystis ΔsigF overproducing mutant	274:365	Previously, we determined the monosaccharidic composition of the polymer of a Synechocystis ΔsigF overproducing mutant.
31233798	4	24	theme	low	700:702	arg1	viscosity					704:712	low viscosity	700:712	low viscosity	700:712	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	7	25	theme	biomedical	1227:1236	arg1	applications					1238:1249	biomedical applications	1227:1249	biomedical applications	1227:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	6	26	theme	high	984:987	arg1	levels					989:994	high levels	984:994	high levels of apoptosis	984:1007	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	4	27	with	structures	588:597	arg1	porosity					609:616	high porosity	604:616	high porosity	604:616	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	4	28	theme	high	604:607	arg1	porosity					609:616	high porosity	604:616	high porosity	604:616	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	7	29	theme	active	1159:1164	arg1	s					1187:1187	biological active carbohydrate polymer(s)	1148:1188	biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1148:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	0	30	theme	antitumor	21:29	arg1	activity					31:38	antitumor activity	21:38	antitumor activity	21:38	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	7	31	theme	sustainable	1122:1132	arg1	production					1134:1143	the sustainable production	1118:1143	the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1118:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	6	32	theme	melanoma	928:935	arg1	viability					915:923	the viability	911:923	the viability of melanoma, thyroid and ovary carcinoma cells	911:970	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	7	33	with	s	1187:1187	arg1	characteristics					1207:1221	the desired characteristics	1195:1221	the desired characteristics for biomedical applications	1195:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	5	34	theme	FTIR	762:765	arg1	analysis					767:774	FTIR analysis	762:774	FTIR analysis	762:774	FTIR analysis confirmed the presence of several functional groups.
31233798	7	35	theme	desired	1199:1205	arg1	characteristics					1207:1221	the desired characteristics	1195:1221	the desired characteristics for biomedical applications	1195:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	4	36	theme	fibrils/lamellar	571:586	arg1	structures					588:597	fibrils/lamellar structures	571:597	fibrils/lamellar structures with high porosity	571:616	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	7	37	theme	ΔsigF	1063:1067	arg1	mutant					1083:1088	the ΔsigF Synechocystis mutant	1059:1088	the ΔsigF Synechocystis mutant	1059:1088	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	7	37	theme	ΔsigF	1063:1067	arg1	platform					1105:1112	a promising platform	1093:1112	a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1093:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	3	38	theme	biomedical	504:513	arg1	research					515:522	biomedical research	504:522	biomedical research	504:522	Here, we further characterized this polymer, demonstrated that it is possible to recover it in high yields, and successfully use it for biomedical research.
31233798	0	39	theme	carbohydrate	61:72	arg1	polymer					74:80	the extracellular carbohydrate polymer	43:80	the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant	43:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	6	40	theme	apoptosis	999:1007	arg1	levels					989:994	high levels	984:994	high levels of apoptosis	984:1007	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	5	41	theme	functional	810:819	arg1	groups					821:826	several functional groups	802:826	several functional groups	802:826	FTIR analysis confirmed the presence of several functional groups.
31233798	7	42	theme	Synechocystis	1069:1081	arg1	mutant					1083:1088	the ΔsigF Synechocystis mutant	1059:1088	the ΔsigF Synechocystis mutant	1059:1088	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	7	42	theme	Synechocystis	1069:1081	arg1	platform					1105:1112	a promising platform	1093:1112	a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1093:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	1	43	theme	Cyanobacterial	134:147	arg1	polymers					176:183	Cyanobacterial extracellular carbohydrate polymers	134:183	Cyanobacterial extracellular carbohydrate polymers	134:183	Cyanobacterial extracellular carbohydrate polymers are particularly attractive for biotechnological applications.
31233798	3	44	theme	high	463:466	arg1	yields					468:473	high yields	463:473	high yields	463:473	Here, we further characterized this polymer, demonstrated that it is possible to recover it in high yields, and successfully use it for biomedical research.
31233798	7	45	theme	promising	1095:1103	arg1	mutant					1083:1088	the ΔsigF Synechocystis mutant	1059:1088	the ΔsigF Synechocystis mutant	1059:1088	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	7	45	theme	promising	1095:1103	arg1	platform					1105:1112	a promising platform	1093:1112	a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1093:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
31233798	2	46	theme	monosaccharidic	278:292	arg1	composition					294:304	the monosaccharidic composition	274:304	the monosaccharidic composition of the polymer of a Synechocystis ΔsigF overproducing mutant	274:365	Previously, we determined the monosaccharidic composition of the polymer of a Synechocystis ΔsigF overproducing mutant.
31233798	1	47	theme	extracellular	149:161	arg1	polymers					176:183	Cyanobacterial extracellular carbohydrate polymers	134:183	Cyanobacterial extracellular carbohydrate polymers	134:183	Cyanobacterial extracellular carbohydrate polymers are particularly attractive for biotechnological applications.
31233798	4	48	theme	structures	588:597	arg1	mesh					563:566	a mesh	561:566	a mesh of fibrils/lamellar structures with high porosity	561:616	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	0	49	from	mutant	126:131	arg1	Characterization					0:15	Characterization	0:15	Characterization	0:15	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	0	49	from	mutant	126:131	arg1	activity					31:38	antitumor activity	21:38	antitumor activity	21:38	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	0	49	from	mutant	126:131	arg1	polymer					74:80	the extracellular carbohydrate polymer	43:80	the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant	43:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	2	50	theme	Synechocystis	326:338	arg1	ΔsigF					340:344	a Synechocystis ΔsigF	324:344	a Synechocystis ΔsigF overproducing mutant	324:365	Previously, we determined the monosaccharidic composition of the polymer of a Synechocystis ΔsigF overproducing mutant.
31233798	1	51	theme	carbohydrate	163:174	arg1	polymers					176:183	Cyanobacterial extracellular carbohydrate polymers	134:183	Cyanobacterial extracellular carbohydrate polymers	134:183	Cyanobacterial extracellular carbohydrate polymers are particularly attractive for biotechnological applications.
31233798	4	52	theme	mass	652:655	arg1	fractions					657:665	high molecular mass fractions	637:665	high molecular mass fractions	637:665	This amorphous polymer is formed by a mesh of fibrils/lamellar structures with high porosity, is constituted by high molecular mass fractions, is highly sulfated and displays low viscosity, even in highly concentrated aqueous solutions.
31233798	5	53	theme	several	802:808	arg1	groups					821:826	several functional groups	802:826	several functional groups	802:826	FTIR analysis confirmed the presence of several functional groups.
31233798	6	54	theme	biological	879:888	arg1	activity					890:897	strong biological activity	872:897	strong biological activity	872:897	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	6	55	theme	carcinoma	956:964	arg1	cells					966:970	ovary carcinoma cells	950:970	ovary carcinoma cells	950:970	We demonstrated that the ΔsigF polymer has strong biological activity, decreasing the viability of melanoma, thyroid and ovary carcinoma cells by inducing high levels of apoptosis, through p53 and caspase-3 activation.
31233798	0	56	theme	polymer	74:80	arg1	Characterization					0:15	Characterization	0:15	Characterization	0:15	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	0	56	theme	polymer	74:80	arg1	activity					31:38	antitumor activity	21:38	antitumor activity	21:38	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	0	57	from	activity	31:38	arg1	mutant					126:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	the cyanobacterium Synechocystis ΔsigF mutant	87:131	Characterization and antitumor activity of the extracellular carbohydrate polymer from the cyanobacterium Synechocystis ΔsigF mutant.
31233798	2	58	theme	polymer	313:319	arg1	composition					294:304	the monosaccharidic composition	274:304	the monosaccharidic composition of the polymer of a Synechocystis ΔsigF overproducing mutant	274:365	Previously, we determined the monosaccharidic composition of the polymer of a Synechocystis ΔsigF overproducing mutant.
31233798	7	59	theme	polymer	1179:1185	arg1	s					1187:1187	biological active carbohydrate polymer(s)	1148:1188	biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications	1148:1249	Therefore, the ΔsigF Synechocystis mutant is a promising platform for the sustainable production of biological active carbohydrate polymer(s) with the desired characteristics for biomedical applications.
30775959	7	0	theme	strain	839:844	arg1	AF10T					846:850	strain AF10T	839:850	strain AF10T	839:850	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	8	1	theme	DNA	947:949	arg1	G+C content					951:961	The genomic DNA G+C content	935:961	The genomic DNA G+C content	935:961	The genomic DNA G+C content was 59.8 mol%.
30775959	8	1	theme	DNA	947:949	arg1	%					975:975	59.8 mol%	967:975	59.8 mol%	967:975	The genomic DNA G+C content was 59.8 mol%.
30775959	9	2	theme	genus	1047:1051	arg1	Granulicella					1053:1064	the genus Granulicella	1043:1064	the genus Granulicella	1043:1064	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	9	2	theme	genus	1047:1051	arg1	Acidobacteriaceae					1074:1090	family Acidobacteriaceae	1067:1090	family Acidobacteriaceae	1067:1090	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	10	3	theme	genus	1354:1358	arg1	sp					1395:1396	the genus Granulicella, Granulicellasibirica sp	1350:1396	the genus Granulicella, Granulicellasibirica sp	1350:1396	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	8	4	theme	genomic	939:945	arg1	G+C content					951:961	The genomic DNA G+C content	935:961	The genomic DNA G+C content	935:961	The genomic DNA G+C content was 59.8 mol%.
30775959	8	4	theme	genomic	939:945	arg1	%					975:975	59.8 mol%	967:975	59.8 mol%	967:975	The genomic DNA G+C content was 59.8 mol%.
30775959	9	5	theme	16S	1118:1120	arg1	similarity					1141:1150	94.4-98.0 % 16S rRNA gene sequence similarity	1106:1150	94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus	1106:1195	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	10	6	theme	novel	1333:1337	arg1	species					1339:1345	a novel species	1331:1345	a novel species of the genus Granulicella, Granulicellasibirica sp	1331:1396	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	3	7	theme	strain	308:313	arg1	AF10T					315:319	strain AF10T	308:319	strain AF10T	308:319	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	4	8	dep	chemoorganotrophic	498:515	arg1	acidophilic					525:535	acidophilic	525:535	acidophilic	525:535	These bacteria were chemoorganotrophic, mildly acidophilic and psychrotolerant, and grew between pH 3.5 and 7.0 (optimum, pH 4.5-5.0) and at temperatures between 2 and 30 °C.
30775959	12	9	theme	type	1451:1454	arg1	strain					1456:1461	the type strain	1447:1461	the type strain	1447:1461	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	12	9	theme	type	1451:1454	arg1	AF10T					1411:1415	Strain AF10T	1404:1415	Strain AF10T (=DSM 104461T=VKM B-3276T)	1404:1442	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	3	10	theme	non-motile	341:350	arg1	rods					352:355	non-motile rods	341:355	non-motile rods	341:355	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	2	11	theme	forested	254:261	arg1	Siberia					290:296	West Siberia	285:296	West Siberia	285:296	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	11	theme	forested	254:261	arg1	tundra					263:268	forested tundra	254:268	forested tundra	254:268	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	11	theme	forested	254:261	arg1	region					277:282	Nadym region	271:282	Nadym region	271:282	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	9	12	theme	Phylogenetic	978:989	arg1	analysis					991:998	Phylogenetic analysis	978:998	Phylogenetic analysis	978:998	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	3	13	theme	AF10T	315:319	arg1	Cells					299:303	Cells	299:303	Cells of strain AF10T	299:319	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	12	14	theme	=DSM	1418:1421	arg1	B-3276T					1435:1441	=DSM 104461T=VKM B-3276T	1418:1441	=DSM 104461T=VKM B-3276T	1418:1441	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	12	14	theme	=DSM	1418:1421	arg1	AF10T					1411:1415	Strain AF10T	1404:1415	Strain AF10T (=DSM 104461T=VKM B-3276T)	1404:1442	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	9	15	theme	94.4-98.0 	1106:1115	arg1	%					1116:1116	%	1116:1116	%	1116:1116	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	10	16	theme	phenotypic	1214:1223	arg1	analyses					1267:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	2	17	dep	aerobic	158:164	arg1	pale-pink					167:175	pale-pink	167:175	pale-pink	167:175	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	3	18	theme	old	464:466	arg1	cultures					468:475	old cultures	464:475	old cultures	464:475	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	10	19	theme	sp	1395:1396	arg1	species					1339:1345	a novel species	1331:1345	a novel species of the genus Granulicella, Granulicellasibirica sp	1331:1396	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	9	20	theme	%	1116:1116	arg1	similarity					1141:1150	94.4-98.0 % 16S rRNA gene sequence similarity	1106:1150	94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus	1106:1195	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	3	21	theme	amorphous	374:382	arg1	substance					418:426	an amorphous extracellular polysaccharide-like substance	371:426	an amorphous extracellular polysaccharide-like substance	371:426	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	3	22	theme	polysaccharide-like	398:416	arg1	substance					418:426	an amorphous extracellular polysaccharide-like substance	371:426	an amorphous extracellular polysaccharide-like substance	371:426	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	8	23	theme	59.8 mol	967:974	arg1	G+C content					951:961	The genomic DNA G+C content	935:961	The genomic DNA G+C content	935:961	The genomic DNA G+C content was 59.8 mol%.
30775959	8	23	theme	59.8 mol	967:974	arg1	%					975:975	59.8 mol%	967:975	59.8 mol%	967:975	The genomic DNA G+C content was 59.8 mol%.
30775959	3	24	from	aggregates	450:459	arg1	cultures					468:475	old cultures	464:475	old cultures	464:475	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	2	25	theme	soil	240:243	arg1	layer					245:249	an organic soil layer	229:249	an organic soil layer in forested tundra, Nadym region, West Siberia	229:296	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	6	26	dep	iso-C15 	750:757	arg1	 0					759:760	 0	759:760	 0	759:760	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	6	26	dep	iso-C15 	750:757	arg1	acid					819:822	13,16-dimethyl octacosanedioic acid	788:822	13,16-dimethyl octacosanedioic acid	788:822	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	6	26	dep	iso-C15 	750:757	arg1	C16 					763:766	C16 	763:766	C16 	763:766	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	0	27	theme	sibirica	13:20	arg1	sp					22:23	Granulicella sibirica sp	0:23	Granulicella sibirica sp.	0:24	Granulicella sibirica sp.
30775959	6	28	theme	octacosanedioic	803:817	arg1	acid					819:822	13,16-dimethyl octacosanedioic acid	788:822	13,16-dimethyl octacosanedioic acid	788:822	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	7	29	from	Mbp	861:863	arg1	size					868:871	size	868:871	size	868:871	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	1	30	theme	organic	82:88	arg1	layer					95:99	an organic soil layer	79:99	an organic soil layer in forested tundra	79:118	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	1	30	theme	organic	82:88	arg1	Siberia					126:132	West Siberia	121:132	West Siberia	121:132	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	9	31	theme	strain	1015:1020	arg1	AF10T					1022:1026	strain AF10T	1015:1026	strain AF10T	1015:1026	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	9	31	theme	strain	1015:1020	arg1	member					1033:1038	a member	1031:1038	a member of the genus Granulicella, family Acidobacteriaceae,	1031:1091	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	3	32	theme	Gram-negative	326:338	arg1	rods					352:355	non-motile rods	341:355	non-motile rods	341:355	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	0	33	theme	Granulicella	0:11	arg1	sp					22:23	Granulicella sibirica sp	0:23	Granulicella sibirica sp.	0:24	Granulicella sibirica sp.
30775959	1	34	attach	isolated	65:72	arg2	acidobacterium					50:63	a psychrotolerant acidobacterium	32:63	a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia	32:132	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	1	34	attach	isolated	65:72	arg1	layer					95:99	an organic soil layer	79:99	an organic soil layer in forested tundra	79:118	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	1	34	attach	isolated	65:72	arg1	Siberia					126:132	West Siberia	121:132	West Siberia	121:132	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	9	35	theme	gene	1127:1130	arg1	similarity					1141:1150	94.4-98.0 % 16S rRNA gene sequence similarity	1106:1150	94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus	1106:1195	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	1	36	theme	soil	90:93	arg1	layer					95:99	an organic soil layer	79:99	an organic soil layer in forested tundra	79:118	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	1	36	theme	soil	90:93	arg1	Siberia					126:132	West Siberia	121:132	West Siberia	121:132	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	10	37	theme	chemotaxonomic	1226:1239	arg1	analyses					1267:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	3	38	theme	extracellular	384:396	arg1	substance					418:426	an amorphous extracellular polysaccharide-like substance	371:426	an amorphous extracellular polysaccharide-like substance	371:426	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	6	39	theme	fatty	733:737	arg1	iso-C15 					750:757	iso-C15 	750:757	iso-C15 	750:757	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	6	39	theme	fatty	733:737	arg1	acids					739:743	The major fatty acids	723:743	The major fatty acids	723:743	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	3	40	theme	large	439:443	arg1	aggregates					450:459	large cell aggregates	439:459	large cell aggregates in old cultures	439:475	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	2	41	theme	Nadym	271:275	arg1	tundra					263:268	forested tundra	254:268	forested tundra	254:268	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	41	theme	Nadym	271:275	arg1	region					277:282	Nadym region	271:282	Nadym region	271:282	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	5	42	theme	preferred	657:665	arg1	sugars					690:695	sugars	690:695	sugars	690:695	The preferred growth substrates were sugars and some polysaccharides.
30775959	5	42	theme	preferred	657:665	arg1	substrates					674:683	The preferred growth substrates	653:683	The preferred growth substrates	653:683	The preferred growth substrates were sugars and some polysaccharides.
30775959	6	43	theme	13,16-dimethyl	788:801	arg1	acid					819:822	13,16-dimethyl octacosanedioic acid	788:822	13,16-dimethyl octacosanedioic acid	788:822	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	6	44	dep	C16 	763:766	arg1	 1∆9 c					777:782	 1∆9 c	777:782	 1∆9 c	777:782	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	6	44	dep	C16 	763:766	arg1	C16 					772:775	C16 	772:775	C16 	772:775	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	3	45	theme	cell	445:448	arg1	aggregates					450:459	large cell aggregates	439:459	large cell aggregates in old cultures	439:475	Cells of strain AF10T were Gram-negative, non-motile rods that produced an amorphous extracellular polysaccharide-like substance and formed large cell aggregates in old cultures.
30775959	10	46	dep	analyses	1267:1274	arg1	the					1201:1203	the	1201:1203	the	1201:1203	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	10	46	dep	analyses	1267:1274	arg1	basis					1205:1209	basis	1205:1209	basis	1205:1209	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	5	47	theme	growth	667:672	arg1	sugars					690:695	sugars	690:695	sugars	690:695	The preferred growth substrates were sugars and some polysaccharides.
30775959	5	47	theme	growth	667:672	arg1	substrates					674:683	The preferred growth substrates	653:683	The preferred growth substrates	653:683	The preferred growth substrates were sugars and some polysaccharides.
30775959	2	48	theme	aerobic	158:164	arg1	bacteria					187:194	strictly aerobic, pale-pink pigmented bacteria	149:194	strictly aerobic, pale-pink pigmented bacteria	149:194	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	49	from	layer	245:249	arg1	Siberia					290:296	West Siberia	285:296	West Siberia	285:296	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	49	from	layer	245:249	arg1	tundra					263:268	forested tundra	254:268	forested tundra	254:268	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	49	from	layer	245:249	arg1	region					277:282	Nadym region	271:282	Nadym region	271:282	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	12	50	theme	Strain	1404:1409	arg1	strain					1456:1461	the type strain	1447:1461	the type strain	1447:1461	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	12	50	theme	Strain	1404:1409	arg1	B-3276T					1435:1441	=DSM 104461T=VKM B-3276T	1418:1441	=DSM 104461T=VKM B-3276T	1418:1441	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	12	50	theme	Strain	1404:1409	arg1	AF10T					1411:1415	Strain AF10T	1404:1415	Strain AF10T (=DSM 104461T=VKM B-3276T)	1404:1442	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	12	51	theme	104461T=VKM	1423:1433	arg1	B-3276T					1435:1441	=DSM 104461T=VKM B-3276T	1418:1441	=DSM 104461T=VKM B-3276T	1418:1441	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	12	51	theme	104461T=VKM	1423:1433	arg1	AF10T					1411:1415	Strain AF10T	1404:1415	Strain AF10T (=DSM 104461T=VKM B-3276T)	1404:1442	Strain AF10T (=DSM 104461T=VKM B-3276T) is the type strain.
30775959	6	52	theme	major	727:731	arg1	iso-C15 					750:757	iso-C15 	750:757	iso-C15 	750:757	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	6	52	theme	major	727:731	arg1	acids					739:743	The major fatty acids	723:743	The major fatty acids	723:743	The major fatty acids were iso-C15 : 0, C16 : 0, C16 : 1∆9 c and 13,16-dimethyl octacosanedioic acid.
30775959	9	53	theme	family	1067:1072	arg1	Granulicella					1053:1064	the genus Granulicella	1043:1064	the genus Granulicella	1043:1064	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	9	53	theme	family	1067:1072	arg1	Acidobacteriaceae					1074:1090	family Acidobacteriaceae	1067:1090	family Acidobacteriaceae	1067:1090	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	9	54	theme	described	1165:1173	arg1	members					1175:1181	currently described members	1155:1181	currently described members of this genus	1155:1195	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	1	55	theme	forested	104:111	arg1	tundra					113:118	forested tundra	104:118	forested tundra	104:118	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	10	56	theme	phylogenetic	1242:1253	arg1	analyses					1267:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	4	57	dep	optimum	591:597	arg1	pH					600:601	pH 4.5-5.0	600:609	pH 4.5-5.0	600:609	These bacteria were chemoorganotrophic, mildly acidophilic and psychrotolerant, and grew between pH 3.5 and 7.0 (optimum, pH 4.5-5.0) and at temperatures between 2 and 30 °C.
30775959	10	58	theme	Granulicellasibirica	1374:1393	arg1	sp					1395:1396	the genus Granulicella, Granulicellasibirica sp	1350:1396	the genus Granulicella, Granulicellasibirica sp	1350:1396	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	7	59	theme	active	919:924	arg1	enzymes					926:932	carbohydrate active enzymes	906:932	carbohydrate active enzymes	906:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	1	60	from	layer	95:99	arg1	tundra					113:118	forested tundra	104:118	forested tundra	104:118	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	9	61	theme	sequence	1132:1139	arg1	similarity					1141:1150	94.4-98.0 % 16S rRNA gene sequence similarity	1106:1150	94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus	1106:1195	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	2	62	theme	bacteria	187:194	arg1	strain					197:202	strain AF10T	197:208	strain AF10T	197:208	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	62	theme	bacteria	187:194	arg1	isolate					138:144	An isolate	135:144	An isolate of strictly aerobic, pale-pink pigmented bacteria	135:194	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	63	theme	organic	232:238	arg1	layer					245:249	an organic soil layer	229:249	an organic soil layer in forested tundra, Nadym region, West Siberia	229:296	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	7	64	theme	enzymes	926:932	arg1	enzymes					926:932	carbohydrate active enzymes	906:932	carbohydrate active enzymes	906:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	7	64	theme	enzymes	926:932	arg1	repertoire					892:901	a wide repertoire	885:901	a wide repertoire of carbohydrate active enzymes	885:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	7	64	theme	enzymes	926:932	arg1	genome					829:834	The genome	825:834	The genome of strain AF10T	825:850	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	1	65	dep	acidobacterium	50:63	arg1	nov.					26:29	nov.	26:29	nov.	26:29	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	7	66	theme	AF10T	846:850	arg1	Mbp					861:863	6.14 Mbp	856:863	6.14 Mbp in size	856:871	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	7	66	theme	AF10T	846:850	arg1	enzymes					926:932	carbohydrate active enzymes	906:932	carbohydrate active enzymes	906:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	7	66	theme	AF10T	846:850	arg1	repertoire					892:901	a wide repertoire	885:901	a wide repertoire of carbohydrate active enzymes	885:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	7	66	theme	AF10T	846:850	arg1	genome					829:834	The genome	825:834	The genome of strain AF10T	825:850	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	9	67	theme	Granulicella	1053:1064	arg1	AF10T					1022:1026	strain AF10T	1015:1026	strain AF10T	1015:1026	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	9	67	theme	Granulicella	1053:1064	arg1	member					1033:1038	a member	1031:1038	a member of the genus Granulicella, family Acidobacteriaceae,	1031:1091	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	2	68	theme	pigmented	177:185	arg1	bacteria					187:194	strictly aerobic, pale-pink pigmented bacteria	149:194	strictly aerobic, pale-pink pigmented bacteria	149:194	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	10	69	theme	genomic	1259:1265	arg1	analyses					1267:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	phenotypic, chemotaxonomic, phylogenetic and genomic analyses	1214:1274	On the basis of phenotypic, chemotaxonomic, phylogenetic and genomic analyses, we propose to classify this bacterium as representing a novel species of the genus Granulicella, Granulicellasibirica sp.
30775959	1	70	theme	West	121:124	arg1	layer					95:99	an organic soil layer	79:99	an organic soil layer in forested tundra	79:118	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	1	70	theme	West	121:124	arg1	Siberia					126:132	West Siberia	121:132	West Siberia	121:132	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	2	71	theme	West	285:288	arg1	Siberia					290:296	West Siberia	285:296	West Siberia	285:296	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	2	71	theme	West	285:288	arg1	tundra					263:268	forested tundra	254:268	forested tundra	254:268	An isolate of strictly aerobic, pale-pink pigmented bacteria, strain AF10T, was obtained from an organic soil layer in forested tundra, Nadym region, West Siberia.
30775959	9	72	theme	genus	1191:1195	arg1	members					1175:1181	currently described members	1155:1181	currently described members of this genus	1155:1195	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	7	73	theme	carbohydrate	906:917	arg1	enzymes					926:932	carbohydrate active enzymes	906:932	carbohydrate active enzymes	906:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	9	74	theme	rRNA	1122:1125	arg1	similarity					1141:1150	94.4-98.0 % 16S rRNA gene sequence similarity	1106:1150	94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus	1106:1195	Phylogenetic analysis indicated that strain AF10T is a member of the genus Granulicella, family Acidobacteriaceae, but displays 94.4-98.0 % 16S rRNA gene sequence similarity to currently described members of this genus.
30775959	1	75	theme	psychrotolerant	34:48	arg1	acidobacterium					50:63	a psychrotolerant acidobacterium	32:63	a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia	32:132	nov., a psychrotolerant acidobacterium isolated from an organic soil layer in forested tundra, West Siberia.
30775959	7	76	theme	wide	887:890	arg1	enzymes					926:932	carbohydrate active enzymes	906:932	carbohydrate active enzymes	906:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	7	76	theme	wide	887:890	arg1	repertoire					892:901	a wide repertoire	885:901	a wide repertoire of carbohydrate active enzymes	885:932	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
30775959	7	76	theme	wide	887:890	arg1	genome					829:834	The genome	825:834	The genome of strain AF10T	825:850	The genome of strain AF10T was 6.14 Mbp in size and encoded a wide repertoire of carbohydrate active enzymes.
29867868	9	0	theme	AIEC	1731:1734	arg1	determinant					1736:1746	a known AIEC determinant	1723:1746	a known AIEC determinant for adhesion to human cells	1723:1774	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	9	0	theme	AIEC	1731:1734	arg1	pili					1717:1720	type 1 pili	1710:1720	type 1 pili	1710:1720	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	8	1	theme	csg	1577:1579	arg1	genes					1581:1585	the csg genes	1573:1585	the csg genes	1573:1585	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	10	2	theme	polysaccharides	1936:1950	arg1	determination					1905:1917	determination	1905:1917	determination of extracellular polysaccharides	1905:1950	To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides.
29867868	10	2	theme	polysaccharides	1936:1950	arg1	assays					1894:1899	biofilm and motility assays	1873:1899	assays	1894:1899	To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides.
29867868	5	3	theme	signaling	1142:1150	arg1	pathway					1152:1158	another major signaling pathway	1128:1158	another major signaling pathway in E. coli	1128:1169	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	3	theme	signaling	1142:1150	arg1	cAMP					1122:1125	cAMP	1122:1125	cAMP	1122:1125	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	8	4	theme	thin	1597:1600	arg1	fimbriae					1614:1621	thin aggregative fimbriae	1597:1621	thin aggregative fimbriae (curli)	1597:1629	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	8	4	theme	thin	1597:1600	arg1	curli					1624:1628	curli	1624:1628	curli	1624:1628	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	12	5	from	inflammation	2493:2504	arg1	CD					2509:2510	CD	2509:2510	CD	2509:2510	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	7	6	from	Growth	1332:1337	arg1	medium					1363:1368	glucose-supplemented medium	1342:1368	glucose-supplemented medium	1342:1368	Growth in glucose-supplemented medium resulted in a reduction in AIEC adhesion to epithelial cells and uptake by macrophages.
29867868	4	7	theme	human	798:802	arg1	macrophages					804:814	human macrophages	798:814	human macrophages	798:814	Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages.
29867868	5	8	from	perturbations	1105:1117	arg1	pathway					1152:1158	another major signaling pathway	1128:1158	another major signaling pathway in E. coli	1128:1169	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	8	from	perturbations	1105:1117	arg1	cAMP					1122:1125	cAMP	1122:1125	cAMP	1122:1125	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	3	9	theme	strain	552:557	arg1	exposure					530:537	exposure	530:537	exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD,	530:659	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	4	10	theme	AIEC	862:865	arg1	determinants					880:891	AIEC cell surface determinants	862:891	AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages	862:971	Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages.
29867868	12	11	theme	gut	2330:2332	arg1	composition					2345:2355	gut microbiota composition	2330:2355	gut microbiota composition	2330:2355	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	0	12	theme	Anti-inflammatory	128:144	arg1	6-Mercaptopurine					151:166	the Anti-inflammatory Drug 6-Mercaptopurine	124:166	the Anti-inflammatory Drug 6-Mercaptopurine	124:166	Phagocytosis and Epithelial Cell Invasion by Crohn's Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine.
29867868	3	13	theme	AIEC	542:545	arg1	strain					552:557	AIEC LF82 strain	542:557	AIEC LF82 strain	542:557	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	4	14	theme	surface	872:878	arg1	determinants					880:891	AIEC cell surface determinants	862:891	AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages	862:971	Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages.
29867868	3	15	theme	human	723:727	arg1	cells					740:744	human epithelial cells	723:744	human epithelial cells	723:744	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	16	theme	6-MP	586:589	arg1	riboside					592:599	amino-6-mercaptopurine (6-MP) riboside	562:599	amino-6-mercaptopurine (6-MP) riboside	562:599	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	16	theme	6-MP	586:589	arg1	drugs					648:652	the most widely used anti-inflammatory drugs	609:652	the most widely used anti-inflammatory drugs in CD	609:658	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	16	theme	6-MP	586:589	arg1	one					602:604	one	602:604	one	602:604	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	1	17	theme	dysbiotic	246:254	arg1	microbiota					256:265	the dysbiotic microbiota	242:265	the dysbiotic microbiota of Crohn's disease (CD) patients	242:298	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	10	18	theme	c-di-GMP	1832:1839	arg1	signaling					1841:1849	c-di-GMP signaling	1832:1849	c-di-GMP signaling in AIEC	1832:1857	To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides.
29867868	5	19	theme	main	982:985	arg1	target					987:992	a main target	980:992	a main target of 6-MP in bacterial cells	980:1019	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	19	theme	main	982:985	arg1	inhibition					1028:1037	the inhibition	1024:1037	the inhibition of the important signal molecule c-di-GMP	1024:1079	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	3	20	theme	amino-6-mercaptopurine	562:583	arg1	riboside					592:599	amino-6-mercaptopurine (6-MP) riboside	562:599	amino-6-mercaptopurine (6-MP) riboside	562:599	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	20	theme	amino-6-mercaptopurine	562:583	arg1	drugs					648:652	the most widely used anti-inflammatory drugs	609:652	the most widely used anti-inflammatory drugs in CD	609:658	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	20	theme	amino-6-mercaptopurine	562:583	arg1	one					602:604	one	602:604	one	602:604	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	5	21	contain	have	1178:1181	arg1	perturbations					1105:1117	perturbations	1105:1117	perturbations in cAMP, another major signaling pathway in E. coli,	1105:1170	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	21	contain	have	1178:1181	arg2	effects					1191:1197	similar effects	1183:1197	similar effects	1183:1197	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	11	22	theme	important	2076:2084	arg1	factor					2096:2101	an important virulence factor	2073:2101	itself an important virulence factor for AIEC	2066:2110	6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC.
29867868	12	23	theme	cell	2180:2183	arg1	interaction					2185:2195	AIEC-host cell interaction	2170:2195	AIEC-host cell interaction	2170:2195	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	6	24	theme	glucose	1278:1284	arg1	presence					1266:1273	the presence	1262:1273	the presence	1262:1273	To this aim, we grew LF82 in the presence of glucose, which leads to inhibition of cAMP synthesis.
29867868	5	25	theme	important	1046:1054	arg1	molecule					1063:1070	the important signal molecule	1042:1070	the important signal molecule c-di-GMP	1042:1079	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	0	26	theme	Escherichia	90:100	arg1	Adherent-Invasive					72:88	Crohn's Disease-Associated Adherent-Invasive Escherichia coli	45:105	Crohn's Disease-Associated Adherent-Invasive Escherichia coli	45:105	Phagocytosis and Epithelial Cell Invasion by Crohn's Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine.
29867868	1	27	theme	inflammation	344:355	arg1	onset					323:327	the onset	319:327	the onset of the chronic inflammation typical of the disease	319:378	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	5	28	theme	similar	1183:1189	arg1	effects					1191:1197	similar effects	1183:1197	similar effects	1183:1197	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	29	with	interactions	1202:1213	arg1	cells					1226:1230	human cells	1220:1230	human cells	1220:1230	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	1	30	theme	disease	372:378	arg1	inflammation					344:355	the chronic inflammation typical	332:363	the chronic inflammation typical of the disease	332:378	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	6	31	theme	synthesis	1321:1329	arg1	inhibition					1302:1311	inhibition	1302:1311	inhibition of cAMP synthesis	1302:1329	To this aim, we grew LF82 in the presence of glucose, which leads to inhibition of cAMP synthesis.
29867868	1	32	theme	patients	291:298	arg1	microbiota					256:265	the dysbiotic microbiota	242:265	the dysbiotic microbiota of Crohn's disease (CD) patients	242:298	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	10	33	from	signaling	1841:1849	arg1	AIEC					1854:1857	AIEC	1854:1857	AIEC	1854:1857	To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides.
29867868	0	34	dep	Escherichia	90:100	arg1	coli					102:105	coli	102:105	coli	102:105	Phagocytosis and Epithelial Cell Invasion by Crohn's Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine.
29867868	2	35	theme	CD	438:439	arg1	treatment					441:449	CD treatment	438:449	CD treatment	438:449	However, the effects of anti-inflammatory drugs used for CD treatment on AIEC virulence have not yet been investigated.
29867868	11	36	dep	itself	2066:2071	arg1	factor					2096:2101	an important virulence factor	2073:2101	itself an important virulence factor for AIEC	2066:2110	6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC.
29867868	0	37	theme	Epithelial	17:26	arg1	Invasion					33:40	Epithelial Cell Invasion	17:40	Epithelial Cell Invasion	17:40	Phagocytosis and Epithelial Cell Invasion by Crohn's Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine.
29867868	9	38	theme	operon	1693:1698	arg1	expression					1671:1680	expression	1671:1680	expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells	1671:1774	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	2	39	theme	anti-inflammatory	405:421	arg1	drugs					423:427	anti-inflammatory drugs	405:427	anti-inflammatory drugs used for CD treatment	405:449	However, the effects of anti-inflammatory drugs used for CD treatment on AIEC virulence have not yet been investigated.
29867868	3	40	dep	ability	673:679	arg1	adhere					684:689	adhere	684:689	to adhere to	681:692	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	40	dep	ability	673:679	arg1	invade					715:720	invade	715:720	invade	715:720	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	7	41	theme	epithelial	1414:1423	arg1	cells					1425:1429	epithelial cells	1414:1429	epithelial cells	1414:1429	Growth in glucose-supplemented medium resulted in a reduction in AIEC adhesion to epithelial cells and uptake by macrophages.
29867868	0	42	theme	Disease-Associated	53:70	arg1	Adherent-Invasive					72:88	Crohn's Disease-Associated Adherent-Invasive Escherichia coli	45:105	Crohn's Disease-Associated Adherent-Invasive Escherichia coli	45:105	Phagocytosis and Epithelial Cell Invasion by Crohn's Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine.
29867868	2	43	theme	AIEC	454:457	arg1	virulence					459:467	AIEC virulence	454:467	AIEC virulence	454:467	However, the effects of anti-inflammatory drugs used for CD treatment on AIEC virulence have not yet been investigated.
29867868	2	44	from	effects	394:400	arg1	virulence					459:467	AIEC virulence	454:467	AIEC virulence	454:467	However, the effects of anti-inflammatory drugs used for CD treatment on AIEC virulence have not yet been investigated.
29867868	10	45	theme	extracellular	1922:1934	arg1	polysaccharides					1936:1950	extracellular polysaccharides	1922:1950	extracellular polysaccharides	1922:1950	To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides.
29867868	8	46	theme	cell	1536:1539	arg1	genes					1558:1562	cell adhesion-related genes	1536:1562	cell adhesion-related genes	1536:1562	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	8	46	theme	cell	1536:1539	arg1	genes					1581:1585	the csg genes	1573:1585	the csg genes	1573:1585	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	6	47	theme	cAMP	1316:1319	arg1	synthesis					1321:1329	cAMP synthesis	1316:1329	cAMP synthesis	1316:1329	To this aim, we grew LF82 in the presence of glucose, which leads to inhibition of cAMP synthesis.
29867868	5	48	theme	c-di-GMP	1072:1079	arg1	inhibition					1028:1037	the inhibition	1024:1037	the inhibition of the important signal molecule c-di-GMP	1024:1079	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	48	theme	c-di-GMP	1072:1079	arg1	target					987:992	a main target	980:992	a main target of 6-MP in bacterial cells	980:1019	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	8	49	theme	genes	1558:1562	arg1	expression					1522:1531	expression	1522:1531	expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli)	1522:1629	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	9	50	theme	known	1725:1729	arg1	determinant					1736:1746	a known AIEC determinant	1723:1746	a known AIEC determinant for adhesion to human cells	1723:1774	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	9	50	theme	known	1725:1729	arg1	pili					1717:1720	type 1 pili	1710:1720	type 1 pili	1710:1720	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	3	51	from	drugs	648:652	arg1	CD					657:658	CD	657:658	CD	657:658	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	1	52	theme	disease	278:284	arg1	patients					291:298	Crohn's disease (CD) patients	270:298	Crohn's disease (CD) patients	270:298	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	5	53	theme	signal	1056:1061	arg1	molecule					1063:1070	the important signal molecule	1042:1070	the important signal molecule c-di-GMP	1042:1079	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	11	54	theme	cellulose	1997:2005	arg1	production					2007:2016	cellulose production	1997:2016	cellulose production	1997:2016	6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC.
29867868	12	55	theme	bacterial	2214:2222	arg1	cell					2224:2227	the bacterial cell	2210:2227	the bacterial cell	2210:2227	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	5	56	theme	major	1136:1140	arg1	pathway					1152:1158	another major signaling pathway	1128:1158	another major signaling pathway in E. coli	1128:1169	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	56	theme	major	1136:1140	arg1	cAMP					1122:1125	cAMP	1122:1125	cAMP	1122:1125	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	7	57	theme	glucose-supplemented	1342:1361	arg1	medium					1363:1368	glucose-supplemented medium	1342:1368	glucose-supplemented medium	1342:1368	Growth in glucose-supplemented medium resulted in a reduction in AIEC adhesion to epithelial cells and uptake by macrophages.
29867868	11	58	theme	biofilm	1975:1981	arg1	formation					1983:1991	biofilm formation	1975:1991	biofilm formation	1975:1991	6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC.
29867868	11	59	theme	cell	2051:2054	arg1	itself					2066:2071	itself	2066:2071	itself	2066:2071	6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC.
29867868	11	59	theme	cell	2051:2054	arg1	motility					2056:2063	cell motility	2051:2063	cell motility	2051:2063	6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC.
29867868	9	60	theme	human	1764:1768	arg1	cells					1770:1774	human cells	1764:1774	human cells	1764:1774	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	5	61	from	target	987:992	arg1	cells					1015:1019	bacterial cells	1005:1019	bacterial cells	1005:1019	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	3	62	theme	LF82	547:550	arg1	strain					552:557	AIEC LF82 strain	542:557	AIEC LF82 strain	542:557	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	5	63	theme	molecule	1063:1070	arg1	c-di-GMP					1072:1079	the important signal molecule c-di-GMP	1042:1079	the important signal molecule c-di-GMP	1042:1079	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	12	64	theme	microbiota	2334:2343	arg1	composition					2345:2355	gut microbiota composition	2330:2355	gut microbiota composition	2330:2355	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	0	65	theme	Drug	146:149	arg1	6-Mercaptopurine					151:166	the Anti-inflammatory Drug 6-Mercaptopurine	124:166	the Anti-inflammatory Drug 6-Mercaptopurine	124:166	Phagocytosis and Epithelial Cell Invasion by Crohn's Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine.
29867868	8	66	theme	aggregative	1602:1612	arg1	fimbriae					1614:1621	thin aggregative fimbriae	1597:1621	thin aggregative fimbriae (curli)	1597:1629	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	8	66	theme	aggregative	1602:1612	arg1	curli					1624:1628	curli	1624:1628	curli	1624:1628	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	5	67	theme	bacterial	1005:1013	arg1	cells					1015:1019	bacterial cells	1005:1019	bacterial cells	1005:1019	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	8	68	with	Consistent	1458:1467	arg1	results					1480:1486	these results	1474:1486	these results	1474:1486	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	4	69	theme	cell	867:870	arg1	determinants					880:891	AIEC cell surface determinants	862:891	AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages	862:971	Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages.
29867868	3	70	theme	epithelial	729:738	arg1	cells					740:744	human epithelial cells	723:744	human epithelial cells	723:744	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	7	71	from	reduction	1384:1392	arg1	adhesion					1402:1409	AIEC adhesion	1397:1409	AIEC adhesion to epithelial cells	1397:1429	Growth in glucose-supplemented medium resulted in a reduction in AIEC adhesion to epithelial cells and uptake by macrophages.
29867868	7	71	from	reduction	1384:1392	arg1	uptake					1435:1440	uptake	1435:1440	uptake by macrophages	1435:1455	Growth in glucose-supplemented medium resulted in a reduction in AIEC adhesion to epithelial cells and uptake by macrophages.
29867868	12	72	theme	AIEC-host	2170:2178	arg1	interaction					2185:2195	AIEC-host cell interaction	2170:2195	AIEC-host cell interaction	2170:2195	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	5	73	from	pathway	1152:1158	arg1	coli					1166:1169	E. coli	1163:1169	E. coli	1163:1169	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	74	theme	6-MP	997:1000	arg1	target					987:992	a main target	980:992	a main target of 6-MP in bacterial cells	980:1019	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	5	74	theme	6-MP	997:1000	arg1	inhibition					1028:1037	the inhibition	1024:1037	the inhibition of the important signal molecule c-di-GMP	1024:1079	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	1	75	theme	Adherent-invasive	169:185	arg1	strains					211:217	Adherent-invasive Escherichia coli (AIEC) strains	169:217	Adherent-invasive Escherichia coli (AIEC) strains	169:217	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	11	76	theme	virulence	2086:2094	arg1	factor					2096:2101	an important virulence factor	2073:2101	itself an important virulence factor for AIEC	2066:2110	6-MP clearly affected biofilm formation and cellulose production, but also, unexpectedly, reduced cell motility, itself an important virulence factor for AIEC.
29867868	1	77	theme	chronic	336:342	arg1	inflammation					344:355	the chronic inflammation typical	332:363	the chronic inflammation typical of the disease	332:378	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	1	78	theme	coli	199:202	arg1	strains					211:217	Adherent-invasive Escherichia coli (AIEC) strains	169:217	Adherent-invasive Escherichia coli (AIEC) strains	169:217	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	4	79	theme	epithelial	927:936	arg1	cells					938:942	epithelial cells	927:942	epithelial cells	927:942	Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages.
29867868	12	80	theme	chronic	2485:2491	arg1	inflammation					2493:2504	chronic inflammation	2485:2504	chronic inflammation in CD	2485:2510	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	10	81	theme	motility	1885:1892	arg1	assays					1894:1899	biofilm and motility assays	1873:1899	assays	1894:1899	To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides.
29867868	1	82	theme	typical	357:363	arg1	inflammation					344:355	the chronic inflammation typical	332:363	the chronic inflammation typical of the disease	332:378	Adherent-invasive Escherichia coli (AIEC) strains are overrepresented in the dysbiotic microbiota of Crohn's disease (CD) patients, and contribute to the onset of the chronic inflammation typical of the disease.
29867868	10	83	theme	biofilm	1873:1879	arg1	assays					1894:1899	biofilm and motility assays	1873:1899	assays	1894:1899	To further investigate whether 6-MP can indeed inhibit c-di-GMP signaling in AIEC, we performed biofilm and motility assays and determination of extracellular polysaccharides.
29867868	12	84	theme	strong	2133:2138	arg1	evidence					2140:2147	strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD	2133:2510	strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD	2133:2510	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	3	85	theme	anti-inflammatory	630:646	arg1	drugs					648:652	the most widely used anti-inflammatory drugs	609:652	the most widely used anti-inflammatory drugs in CD	609:658	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	5	86	theme	human	1220:1224	arg1	cells					1226:1230	human cells	1220:1230	human cells	1220:1230	Since a main target of 6-MP in bacterial cells is the inhibition of the important signal molecule c-di-GMP, we also tested whether perturbations in cAMP, another major signaling pathway in E. coli, might have similar effects on interactions with human cells.
29867868	0	87	theme	Cell	28:31	arg1	Invasion					33:40	Epithelial Cell Invasion	17:40	Epithelial Cell Invasion	17:40	Phagocytosis and Epithelial Cell Invasion by Crohn's Disease-Associated Adherent-Invasive Escherichia coli Are Inhibited by the Anti-inflammatory Drug 6-Mercaptopurine.
29867868	9	88	theme	fim	1689:1691	arg1	operon					1693:1698	the fim operon	1685:1698	the fim operon	1685:1698	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	2	89	theme	drugs	423:427	arg1	effects					394:400	the effects	390:400	the effects of anti-inflammatory drugs used for CD treatment on AIEC virulence	390:467	However, the effects of anti-inflammatory drugs used for CD treatment on AIEC virulence have not yet been investigated.
29867868	9	90	theme	type	1710:1713	arg1	determinant					1736:1746	a known AIEC determinant	1723:1746	a known AIEC determinant for adhesion to human cells	1723:1774	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	9	90	theme	type	1710:1713	arg1	pili					1717:1720	type 1 pili	1710:1720	type 1 pili	1710:1720	In addition, glucose strongly inhibits expression of the fim operon, encoding type 1 pili, a known AIEC determinant for adhesion to human cells.
29867868	12	91	theme	CD	2299:2300	arg1	remission					2302:2310	CD remission	2299:2310	CD remission	2299:2310	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	3	92	theme	drugs	648:652	arg1	riboside					592:599	amino-6-mercaptopurine (6-MP) riboside	562:599	amino-6-mercaptopurine (6-MP) riboside	562:599	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	92	theme	drugs	648:652	arg1	drugs					648:652	the most widely used anti-inflammatory drugs	609:652	the most widely used anti-inflammatory drugs in CD	609:658	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	3	92	theme	drugs	648:652	arg1	one					602:604	one	602:604	one	602:604	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	4	93	theme	LF82	772:775	arg1	phagocytosis					756:767	phagocytosis	756:767	phagocytosis of LF82 treated with 6-MP by human macrophages	756:814	Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages.
29867868	8	94	theme	adhesion-related	1541:1556	arg1	genes					1558:1562	cell adhesion-related genes	1536:1562	cell adhesion-related genes	1536:1562	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	8	94	theme	adhesion-related	1541:1556	arg1	genes					1581:1585	the csg genes	1573:1585	the csg genes	1573:1585	Consistent with these results, both 6-MP and glucose can affect expression of cell adhesion-related genes, such as the csg genes, encoding thin aggregative fimbriae (curli).
29867868	4	95	with	interaction	910:920	arg1	cells					938:942	epithelial cells	927:942	epithelial cells	927:942	Notably, phagocytosis of LF82 treated with 6-MP by human macrophages is also reduced, suggesting that 6-MP affects AIEC cell surface determinants involved both in interaction with epithelial cells and in uptake by macrophages.
29867868	12	96	theme	bacterial	2418:2426	arg1	virulence					2428:2436	bacterial virulence	2418:2436	bacterial virulence	2418:2436	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29867868	3	97	theme	used	625:628	arg1	drugs					648:652	the most widely used anti-inflammatory drugs	609:652	the most widely used anti-inflammatory drugs in CD	609:658	In this report, we show that exposure of AIEC LF82 strain to amino-6-mercaptopurine (6-MP) riboside, one of the most widely used anti-inflammatory drugs in CD, impairs its ability to adhere to, and consequently to invade, human epithelial cells.
29867868	7	98	theme	AIEC	1397:1400	arg1	adhesion					1402:1409	AIEC adhesion	1397:1409	AIEC adhesion to epithelial cells	1397:1429	Growth in glucose-supplemented medium resulted in a reduction in AIEC adhesion to epithelial cells and uptake by macrophages.
29867868	12	99	theme	novel	2396:2400	arg1	drugs					2402:2406	novel drugs	2396:2406	novel drugs targeting bacterial virulence and signaling	2396:2450	Our results provide strong evidence that 6-MP can affect AIEC-host cell interaction by acting on the bacterial cell, thus strengthening the hypothesis that mercaptopurines might promote CD remission also by affecting gut microbiota composition and/or physiology, and suggesting that novel drugs targeting bacterial virulence and signaling might be effective in preventing chronic inflammation in CD.
29407701	4	0	theme	bound	979:983	arg1	LB-EPSs					991:997	LB-EPSs	991:997	LB-EPSs	991:997	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	4	0	theme	bound	979:983	arg1	EPSs					985:988	loosely bound EPSs	971:988	loosely bound EPSs (LB-EPSs)	971:998	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	7	1	theme	CeO2	1606:1609	arg1	NPs					1611:1613	CeO2 NPs	1606:1613	CeO2 NPs	1606:1613	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	2	2	theme	polymeric	624:632	arg1	EPSs					646:649	EPSs	646:649	EPSs	646:649	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	2	2	theme	polymeric	624:632	arg1	substances					634:643	stratified extracellular polymeric substances	599:643	stratified extracellular polymeric substances (EPSs)	599:650	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	1	3	theme	accelerated	160:170	arg1	application					172:182	the accelerated application	156:182	the accelerated application of CeO2 nanoparticles (NPs)	156:210	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	5	4	theme	α-helix+3-turn	1196:1209	arg1	value					1226:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	3	5	theme	PS	857:858	arg1	breadth					828:834	breadth	828:834	breadth	828:834	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	3	5	theme	PS	857:858	arg1	production					813:822	production	813:822	production	813:822	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	3	5	theme	PS	857:858	arg1	response					896:903	a response	894:903	a response to 10 mg/L CeO2 NPs	894:923	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	0	6	theme	Structural	73:82	arg1	properties					115:124	Structural, physicochemical and microbial properties	73:124	Structural, physicochemical and microbial properties	73:124	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	2	7	theme	extracellular	610:622	arg1	EPSs					646:649	EPSs	646:649	EPSs	646:649	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	2	7	theme	extracellular	610:622	arg1	substances					634:643	stratified extracellular polymeric substances	599:643	stratified extracellular polymeric substances (EPSs)	599:650	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	4	8	theme	molecular	1055:1063	arg1	AMW					1073:1075	AMW	1073:1075	AMW	1073:1075	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	4	8	theme	molecular	1055:1063	arg1	weight					1065:1070	apparent molecular weight	1046:1070	apparent molecular weight (AMW)	1046:1076	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	1	9	theme	CeO2	267:270	arg1	NPs					272:274	CeO2 NPs	267:274	CeO2 NPs	267:274	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	6	10	theme	CeO2	1308:1311	arg1	NPs					1313:1315	CeO2 NPs	1308:1315	CeO2 NPs	1308:1315	Furthermore, long-term exposure to CeO2 NPs decreased cell viability, reduced microbial diversity and shifted the microbial composition.
29407701	5	11	theme	TB-EPSs	1235:1241	arg1	value					1226:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	5	11	theme	TB-EPSs	1235:1241	arg1	content					1183:1189	acetyl content	1176:1189	acetyl content	1176:1189	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	2	12	theme	stratified	599:608	arg1	EPSs					646:649	EPSs	646:649	EPSs	646:649	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	2	12	theme	stratified	599:608	arg1	substances					634:643	stratified extracellular polymeric substances	599:643	stratified extracellular polymeric substances (EPSs)	599:650	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	4	13	theme	apparent	1046:1053	arg1	AMW					1073:1075	AMW	1073:1075	AMW	1073:1075	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	4	13	theme	apparent	1046:1053	arg1	weight					1065:1070	apparent molecular weight	1046:1070	apparent molecular weight (AMW)	1046:1076	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	7	14	theme	PS-regulated	1532:1543	arg1	control					1545:1551	PS-regulated control	1532:1551	PS-regulated control	1532:1551	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	0	15	theme	physicochemical	85:99	arg1	properties					115:124	Structural, physicochemical and microbial properties	73:124	Structural, physicochemical and microbial properties	73:124	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	7	16	theme	N-acylated-l-homoserine	1410:1432	arg1	concentrations					1442:1455	N-acylated-l-homoserine lactone concentrations	1410:1455	N-acylated-l-homoserine lactone concentrations	1410:1455	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	3	17	theme	CeO2	916:919	arg1	NPs					921:923	10 mg/L CeO2 NPs	908:923	10 mg/L CeO2 NPs	908:923	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	3	18	theme	β-d-glucopyranose	839:855	arg1	PS					857:858	β-d-glucopyranose PS	839:858	β-d-glucopyranose PS	839:858	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	2	19	theme	NPs	520:522	arg1	concentrations					524:537	different CeO2 NPs concentrations	505:537	different CeO2 NPs concentrations	505:537	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	3	20	theme	α-d-glucopyranose	745:761	arg1	PS					780:781	PS	780:781	PS	780:781	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	3	20	theme	α-d-glucopyranose	745:761	arg1	polysaccharides					763:777	α-d-glucopyranose polysaccharides	745:777	α-d-glucopyranose polysaccharides (PS)	745:782	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	6	21	theme	microbial	1351:1359	arg1	diversity					1361:1369	microbial diversity	1351:1369	microbial diversity	1351:1369	Furthermore, long-term exposure to CeO2 NPs decreased cell viability, reduced microbial diversity and shifted the microbial composition.
29407701	4	22	theme	lower	1088:1092	arg1	abundance					1094:1102	a lower abundance	1086:1102	a lower abundance	1086:1102	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	0	23	theme	microbial	105:113	arg1	properties					115:124	Structural, physicochemical and microbial properties	73:124	Structural, physicochemical and microbial properties	73:124	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	7	24	theme	increased	1472:1480	arg1	density					1482:1488	increased density	1472:1488	increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs	1472:1613	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	4	25	dep	macromolecules	1016:1029	arg1	increasing					1032:1041	increasing	1032:1041	increasing in apparent molecular weight (AMW)	1032:1076	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	1	26	theme	CeO2	187:190	arg1	nanoparticles					192:204	CeO2 nanoparticles	187:204	CeO2 nanoparticles (NPs)	187:210	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	1	26	theme	CeO2	187:190	arg1	NPs					207:209	NPs	207:209	NPs	207:209	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	6	27	theme	microbial	1387:1395	arg1	composition					1397:1407	the microbial composition	1383:1407	the microbial composition	1383:1407	Furthermore, long-term exposure to CeO2 NPs decreased cell viability, reduced microbial diversity and shifted the microbial composition.
29407701	8	28	theme	environmental	1685:1697	arg1	stress					1699:1704	environmental stress	1685:1704	environmental stress caused by NPs	1685:1718	These results expand the understanding of how microaggregates resist environmental stress caused by NPs.
29407701	3	29	theme	CeO2	682:685	arg1	NPs					687:689	0.1 mg/L CeO2 NPs	673:689	0.1 mg/L CeO2 NPs	673:689	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	3	30	theme	10 mg/L	908:914	arg1	NPs					921:923	10 mg/L CeO2 NPs	908:923	10 mg/L CeO2 NPs	908:923	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	1	31	theme	nanoparticles	192:204	arg1	application					172:182	the accelerated application	156:182	the accelerated application of CeO2 nanoparticles (NPs)	156:210	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	2	32	theme	biofilms	463:470	arg1	properties					438:447	the structural, physicochemical and microbial properties	392:447	the structural, physicochemical and microbial properties of wastewater biofilms	392:470	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	7	33	theme	lactone	1434:1440	arg1	concentrations					1442:1455	N-acylated-l-homoserine lactone concentrations	1410:1455	N-acylated-l-homoserine lactone concentrations	1410:1455	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	2	34	theme	substances	634:643	arg1	mechanisms					585:594	the protective mechanisms	570:594	the protective mechanisms of stratified extracellular polymeric substances (EPSs)	570:650	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	2	35	from	responses	379:387	arg1	properties					438:447	the structural, physicochemical and microbial properties	392:447	the structural, physicochemical and microbial properties of wastewater biofilms	392:470	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	7	36	theme	Pseudomonas	1493:1503	arg1	density					1482:1488	increased density	1472:1488	increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs	1472:1613	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	2	37	theme	wastewater	452:461	arg1	biofilms					463:470	wastewater biofilms	452:470	wastewater biofilms	452:470	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	3	38	theme	increased	803:811	arg1	breadth					828:834	breadth	828:834	breadth	828:834	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	3	38	theme	increased	803:811	arg1	production					813:822	production	813:822	production	813:822	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	3	38	theme	increased	803:811	arg1	response					896:903	a response	894:903	a response to 10 mg/L CeO2 NPs	894:923	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	0	39	theme	potential	130:138	arg1	mechanism					140:148	potential mechanism	130:148	potential mechanism	130:148	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	6	40	theme	long-term	1286:1294	arg1	exposure					1296:1303	long-term exposure	1286:1303	long-term exposure to CeO2 NPs	1286:1315	Furthermore, long-term exposure to CeO2 NPs decreased cell viability, reduced microbial diversity and shifted the microbial composition.
29407701	2	41	theme	physicochemical	408:422	arg1	properties					438:447	the structural, physicochemical and microbial properties	392:447	the structural, physicochemical and microbial properties of wastewater biofilms	392:470	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	0	42	theme	wastewater	13:22	arg1	biofilms					24:31	wastewater biofilms	13:31	wastewater biofilms	13:31	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	3	43	theme	polysaccharides	763:777	arg1	distribution					729:740	the distribution	725:740	the distribution of α-d-glucopyranose polysaccharides (PS)	725:782	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	2	44	theme	particular	547:556	arg1	emphasis					558:565	a particular emphasis	545:565	a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs)	545:650	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	5	45	dep	content	1183:1189	arg1	The					1172:1174	The	1172:1174	The	1172:1174	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	2	46	theme	microbial	428:436	arg1	properties					438:447	the structural, physicochemical and microbial properties	392:447	the structural, physicochemical and microbial properties of wastewater biofilms	392:470	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	0	47	theme	chronic	36:42	arg1	exposure					63:70	chronic CeO2 nanoparticles exposure	36:70	chronic CeO2 nanoparticles exposure	36:70	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	1	48	theme	CeO2	301:304	arg1	NPs					306:308	CeO2 NPs	301:308	CeO2 NPs	301:308	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	5	49	theme	helix	1211:1215	arg1	value					1226:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	5	50	theme	CeO2	1263:1266	arg1	NPs					1268:1270	CeO2 NPs	1263:1270	CeO2 NPs	1263:1270	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	5	51	theme	/β-sheet	1217:1224	arg1	value					1226:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	(α-helix+3-turn helix)/β-sheet value	1195:1230	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	4	52	dep	aggregated	1000:1009	arg1	whereas					1105:1111	whereas	1105:1111	whereas	1105:1111	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	0	53	theme	biofilms	24:31	arg1	Responses					0:8	Responses	0:8	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.	0:149	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	4	54	theme	bound	1140:1144	arg1	TB-EPSs					1152:1158	TB-EPSs	1152:1158	TB-EPSs	1152:1158	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	4	54	theme	bound	1140:1144	arg1	EPSs					1146:1149	tightly bound EPSs	1132:1149	tightly bound EPSs (TB-EPSs)	1132:1159	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	2	55	theme	CeO2	515:518	arg1	concentrations					524:537	different CeO2 NPs concentrations	505:537	different CeO2 NPs concentrations	505:537	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	0	56	theme	nanoparticles	49:61	arg1	exposure					63:70	chronic CeO2 nanoparticles exposure	36:70	chronic CeO2 nanoparticles exposure	36:70	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	3	57	theme	Chronic	653:659	arg1	exposure					661:668	Chronic exposure	653:668	Chronic exposure to 0.1 mg/L CeO2 NPs	653:689	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	0	58	theme	CeO2	44:47	arg1	exposure					63:70	chronic CeO2 nanoparticles exposure	36:70	chronic CeO2 nanoparticles exposure	36:70	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	1	59	theme	encounter	313:321	arg1	microaggregates					323:337	encounter microaggregates	313:337	encounter microaggregates	313:337	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	2	60	theme	protective	574:583	arg1	mechanisms					585:594	the protective mechanisms	570:594	the protective mechanisms of stratified extracellular polymeric substances (EPSs)	570:650	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	2	61	theme	chronic	475:481	arg1	exposure					483:490	chronic exposure	475:490	chronic exposure (75 days) to different CeO2 NPs concentrations	475:537	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	2	61	theme	chronic	475:481	arg1	days					496:499	75 days	493:499	75 days	493:499	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	4	62	theme	CeO2	961:964	arg1	NPs					966:968	CeO2 NPs	961:968	CeO2 NPs	961:968	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	7	63	from	production	1572:1581	arg1	EPSs					1586:1589	EPSs	1586:1589	EPSs	1586:1589	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	1	64	theme	treatment	224:232	arg1	plants					234:239	wastewater treatment plants	213:239	wastewater treatment plants	213:239	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	3	65	theme	0.1 mg/L	673:680	arg1	NPs					687:689	0.1 mg/L CeO2 NPs	673:689	0.1 mg/L CeO2 NPs	673:689	Chronic exposure to 0.1 mg/L CeO2 NPs boosted the content and broadened the distribution of α-d-glucopyranose polysaccharides (PS), while the sharply increased production and breadth of β-d-glucopyranose PS, forming a formidable shield, was a response to 10 mg/L CeO2 NPs.
29407701	4	66	from	AMW	1125:1127	arg1	TB-EPSs					1152:1158	TB-EPSs	1152:1158	TB-EPSs	1152:1158	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	4	66	from	AMW	1125:1127	arg1	EPSs					1146:1149	tightly bound EPSs	1132:1149	tightly bound EPSs (TB-EPSs)	1132:1159	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	4	67	theme	average	1117:1123	arg1	AMW					1125:1127	the average AMW	1113:1127	the average AMW in tightly bound EPSs (TB-EPSs)	1113:1159	After the bacteria were exposed to CeO2 NPs, loosely bound EPSs (LB-EPSs) aggregated into macromolecules (increasing in apparent molecular weight (AMW)) but at a lower abundance, whereas the average AMW in tightly bound EPSs (TB-EPSs) decreased.
29407701	5	68	theme	acetyl	1176:1181	arg1	content					1183:1189	acetyl content	1176:1189	acetyl content	1176:1189	The acetyl content and (α-helix+3-turn helix)/β-sheet value of TB-EPSs increased to resist CeO2 NPs.
29407701	2	69	theme	different	505:513	arg1	concentrations					524:537	different CeO2 NPs concentrations	505:537	different CeO2 NPs concentrations	505:537	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	1	70	theme	wastewater	213:222	arg1	plants					234:239	wastewater treatment plants	213:239	wastewater treatment plants	213:239	With the accelerated application of CeO2 nanoparticles (NPs), wastewater treatment plants will increasingly receive CeO2 NPs, thus inevitably causing CeO2 NPs to encounter microaggregates.
29407701	7	71	dep	NPs	1611:1613	arg1	response					1594:1601	response	1594:1601	response	1594:1601	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
29407701	2	72	theme	structural	396:405	arg1	properties					438:447	the structural, physicochemical and microbial properties	392:447	the structural, physicochemical and microbial properties of wastewater biofilms	392:470	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	2	73	from	emphasis	558:565	arg1	mechanisms					585:594	the protective mechanisms	570:594	the protective mechanisms of stratified extracellular polymeric substances (EPSs)	570:650	Here, we comprehensively elucidate the responses in the structural, physicochemical and microbial properties of wastewater biofilms to chronic exposure (75 days) to different CeO2 NPs concentrations, with a particular emphasis on the protective mechanisms of stratified extracellular polymeric substances (EPSs).
29407701	6	74	theme	cell	1327:1330	arg1	viability					1332:1340	cell viability	1327:1340	cell viability	1327:1340	Furthermore, long-term exposure to CeO2 NPs decreased cell viability, reduced microbial diversity and shifted the microbial composition.
29407701	0	75	dep	Responses	0:8	arg1	mechanism					140:148	potential mechanism	130:148	potential mechanism	130:148	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	0	75	dep	Responses	0:8	arg1	properties					115:124	Structural, physicochemical and microbial properties	73:124	Structural, physicochemical and microbial properties	73:124	Responses of wastewater biofilms to chronic CeO2 nanoparticles exposure: Structural, physicochemical and microbial properties and potential mechanism.
29407701	7	76	theme	PS	1569:1570	arg1	production					1572:1581	PS production	1569:1581	PS production in EPSs	1569:1589	N-acylated-l-homoserine lactone concentrations increased with increased density of Pseudomonas, which was associated with PS-regulated control, thus promoting PS production in EPSs in response to CeO2 NPs.
30889210	7	0	theme	quantitative	1298:1309	arg1	spectrometry					1316:1327	quantitative mass spectrometry	1298:1327	quantitative mass spectrometry	1298:1327	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	3	1	from	changes	725:731	arg1	taxa					744:747	diverse taxa	736:747	diverse taxa	736:747	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa.
30889210	10	2	theme	relative	1822:1829	arg1	abundance					1831:1839	the relative abundance	1818:1839	the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways	1818:1896	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	12	3	theme	medicinal	2140:2148	arg1	taxa					2163:2166	medicinal herb-induced taxa	2140:2166	medicinal herb-induced taxa	2140:2166	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	9	4	theme	fermentation	1746:1757	arg1	capable					1709:1715	capable	1709:1715	capable	1709:1715	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	2	5	theme	fecal	299:303	arg1	cultivation					305:315	anaerobic human fecal cultivation	283:315	anaerobic human fecal cultivation	283:315	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	2	6	theme	anaerobic	283:291	arg1	cultivation					305:315	anaerobic human fecal cultivation	283:315	anaerobic human fecal cultivation	283:315	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	12	7	theme	potential	2100:2108	arg1	interactions					2121:2132	potential functional interactions	2100:2132	potential functional interactions among medicinal herb-induced taxa	2100:2166	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	2	8	from	treatment	373:381	arg1	disease					410:416	disease	410:416	disease	410:416	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	2	8	from	treatment	373:381	arg1	health					399:404	neurological health	386:404	neurological health	386:404	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	2	9	used	used	278:281	arg2	We					265:266	We	265:266	We	265:266	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	11	10	theme	network	1913:1919	arg1	analyses					1921:1928	Co-occurrence network analyses	1899:1928	Co-occurrence network analyses	1899:1928	Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures.
30889210	7	11	theme	fatty	1160:1164	arg1	acid					1166:1169	short chain fatty acid	1148:1169	short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1148:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	11	theme	fatty	1160:1164	arg1	SCFA					1172:1175	SCFA	1172:1175	SCFA	1172:1175	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	12	with	taxa	1226:1229	arg1	analysis					1263:1270	monosaccharide composition analysis	1236:1270	monosaccharide composition analysis of each medicinal herb	1236:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	13	theme	short	1148:1152	arg1	acid					1166:1169	short chain fatty acid	1148:1169	short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1148:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	13	theme	short	1148:1152	arg1	SCFA					1172:1175	SCFA	1172:1175	SCFA	1172:1175	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	11	14	theme	herb	1983:1986	arg1	cultures					1988:1995	medicinal herb cultures	1973:1995	medicinal herb cultures	1973:1995	Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures.
30889210	1	15	theme	nervine	213:219	arg1	medicines					228:236	nervine herbal medicines	213:236	nervine herbal medicines	213:236	The prebiotic potential of nervine herbal medicines has been scarcely studied.
30889210	8	16	theme	glycan	1535:1540	arg1	catabolism					1542:1551	both protein and glycan catabolism	1518:1551	catabolism	1542:1551	Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species.
30889210	11	17	theme	large	1943:1947	arg1	number					1949:1954	a large number	1941:1954	a large number of taxa pairs	1941:1968	Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures.
30889210	7	18	theme	utilization	1132:1142	arg1	reconstruction					1108:1121	genome reconstruction	1101:1121	genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1101:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	1	19	theme	medicines	228:236	arg1	potential					200:208	The prebiotic potential	186:208	The prebiotic potential of nervine herbal medicines	186:236	The prebiotic potential of nervine herbal medicines has been scarcely studied.
30889210	6	20	theme	Additional	1014:1023	arg1	species					1025:1031	Additional species	1014:1031	Additional species	1014:1031	Additional species were impacted in an herb-specific manner.
30889210	4	21	theme	coordinate	760:769	arg1	analysis					771:778	Principal coordinate analysis	750:778	Principal coordinate analysis	750:778	Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential.
30889210	8	22	theme	amino	1564:1568	arg1	acid					1570:1573	amino acid and sugar substrates	1564:1594	acid	1570:1573	Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species.
30889210	10	23	dep	pathways	1889:1896	arg1	propionate					1877:1886	propionate	1877:1886	propionate	1877:1886	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	10	23	dep	pathways	1889:1896	arg1	butyrate					1864:1871	butyrate	1864:1871	butyrate	1864:1871	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	10	23	dep	pathways	1889:1896	arg1	pathways					1889:1896	SCFA (butyrate and propionate) pathways	1858:1896	SCFA (butyrate and propionate) pathways	1858:1896	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	7	24	theme	genome	1101:1106	arg1	reconstruction					1108:1121	genome reconstruction	1101:1121	genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1101:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	25	theme	microbiota	1427:1436	arg1	restructuring					1438:1450	microbiota restructuring	1427:1450	microbiota restructuring	1427:1450	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	0	26	theme	community	57:65	arg1	interactions					77:88	community metabolic interactions	57:88	community metabolic interactions	57:88	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	0	27	theme	gene	9:12	arg1	profiling					14:22	16S rRNA gene profiling	0:22	16S rRNA gene profiling	0:22	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	12	28	dep	cultures	2078:2085	arg1	replicate					2068:2076	replicate	2068:2076	replicate	2068:2076	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	0	29	theme	as	171:172	arg1	nootropics					174:183	as nootropics	171:183	as nootropics	171:183	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	7	30	theme	medicinal	1280:1288	arg1	herb					1290:1293	each medicinal herb	1275:1293	each medicinal herb	1275:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	5	31	theme	species	980:986	arg1	species					980:986	the 243 enumerated species	961:986	the 243 enumerated species	961:986	The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs.
30889210	5	31	theme	species	980:986	arg1	one-third					948:956	one-third	948:956	one-third	948:956	The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs.
30889210	0	32	theme	prebiotic	94:102	arg1	potential					104:112	prebiotic potential	94:112	prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics	94:183	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	12	33	theme	culture	2036:2042	arg1	relationships					2051:2063	related culture growth relationships	2028:2063	related culture growth relationships	2028:2063	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	6	34	theme	herb-specific	1053:1065	arg1	manner					1067:1072	an herb-specific manner	1050:1072	an herb-specific manner	1050:1072	Additional species were impacted in an herb-specific manner.
30889210	4	35	theme	unique	830:835	arg1	communities					847:857	unique microbial communities	830:857	unique microbial communities predicted to display unique metabolic potential	830:905	Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential.
30889210	7	36	theme	composition	1251:1261	arg1	analysis					1263:1270	monosaccharide composition analysis	1236:1270	monosaccharide composition analysis of each medicinal herb	1236:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	2	37	theme	gut	481:483	arg1	microbiota					485:494	gut microbiota	481:494	gut microbiota	481:494	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	0	38	theme	metabolic	67:75	arg1	interactions					77:88	community metabolic interactions	57:88	community metabolic interactions	57:88	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	0	39	theme	16S	0:2	arg1	rRNA					4:7	16S rRNA	0:7	16S rRNA gene profiling	0:22	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	9	40	theme	efficient	1667:1675	arg1	taxa					1653:1656	taxa	1653:1656	taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation	1653:1757	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	9	40	theme	efficient	1667:1675	arg1	fermenters					1688:1697	efficient amino acid fermenters	1667:1697	efficient amino acid fermenters	1667:1697	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	7	41	theme	potential	1406:1414	arg1	drivers					1416:1422	potential drivers	1406:1422	potential drivers of microbiota restructuring	1406:1450	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	2	42	theme	medicine	463:470	arg1	Ayurveda					421:428	Ayurveda	421:428	Ayurveda	421:428	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	2	42	theme	medicine	463:470	arg1	systems					452:458	other traditional systems	434:458	other traditional systems	434:458	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	4	43	theme	unique	880:885	arg1	potential					897:905	unique metabolic potential	880:905	unique metabolic potential	880:905	Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential.
30889210	7	44	theme	profiled	1217:1224	arg1	taxa					1226:1229	216 profiled taxa	1213:1229	216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1213:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	2	45	theme	human	293:297	arg1	cultivation					305:315	anaerobic human fecal cultivation	283:315	anaerobic human fecal cultivation	283:315	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	9	46	theme	acid	1683:1686	arg1	taxa					1653:1656	taxa	1653:1656	taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation	1653:1757	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	9	46	theme	acid	1683:1686	arg1	fermenters					1688:1697	efficient amino acid fermenters	1667:1697	efficient amino acid fermenters	1667:1697	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	3	47	theme	rRNA	691:694	arg1	sequencing					696:705	16S rRNA sequencing	687:705	16S rRNA sequencing	687:705	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa.
30889210	8	48	theme	gut	1493:1495	arg1	microbiota					1497:1506	gut microbiota	1493:1506	gut microbiota	1493:1506	Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species.
30889210	10	49	theme	microbial	1773:1781	arg1	communities					1783:1793	Herb-induced microbial communities	1760:1793	Herb-induced microbial communities	1760:1793	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	7	50	theme	microbial	1372:1380	arg1	communities					1382:1392	resulting microbial communities	1362:1392	resulting microbial communities	1362:1392	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	11	51	theme	pairs	1964:1968	arg1	number					1949:1954	a large number	1941:1954	a large number of taxa pairs	1941:1968	Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures.
30889210	4	52	theme	communities	847:857	arg1	formation					817:825	the formation	813:825	the formation of unique microbial communities predicted to display unique metabolic potential	813:905	Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential.
30889210	3	53	theme	fecal	510:514	arg1	cultures					516:523	fecal cultures	510:523	fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari	510:682	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa.
30889210	10	54	theme	taxa	1844:1847	arg1	abundance					1831:1839	the relative abundance	1818:1839	the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways	1818:1896	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	9	55	theme	acid	1731:1734	arg1	capable					1709:1715	capable	1709:1715	capable	1709:1715	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	7	56	theme	pathways	1178:1185	arg1	reconstruction					1108:1121	genome reconstruction	1101:1121	genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1101:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	11	57	theme	medicinal	1973:1981	arg1	cultures					1988:1995	medicinal herb cultures	1973:1995	medicinal herb cultures	1973:1995	Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures.
30889210	9	58	theme	sugar	1740:1744	arg1	fermentation					1746:1757	sugar fermentation	1740:1757	sugar fermentation	1740:1757	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	7	59	theme	mass	1311:1314	arg1	spectrometry					1316:1327	quantitative mass spectrometry	1298:1327	quantitative mass spectrometry	1298:1327	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	3	60	theme	diverse	736:742	arg1	taxa					744:747	diverse taxa	736:747	diverse taxa	736:747	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa.
30889210	7	61	theme	acid	1166:1169	arg1	pathways					1178:1185	short chain fatty acid (SCFA) pathways	1148:1185	short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1148:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	10	62	theme	SCFA	1858:1861	arg1	propionate					1877:1886	propionate	1877:1886	propionate	1877:1886	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	10	62	theme	SCFA	1858:1861	arg1	butyrate					1864:1871	butyrate	1864:1871	butyrate	1864:1871	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	10	62	theme	SCFA	1858:1861	arg1	pathways					1889:1896	SCFA (butyrate and propionate) pathways	1858:1896	SCFA (butyrate and propionate) pathways	1858:1896	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	1	63	theme	prebiotic	190:198	arg1	potential					200:208	The prebiotic potential	186:208	The prebiotic potential of nervine herbal medicines	186:236	The prebiotic potential of nervine herbal medicines has been scarcely studied.
30889210	12	64	theme	herb-induced	2150:2161	arg1	taxa					2163:2166	medicinal herb-induced taxa	2140:2166	medicinal herb-induced taxa	2140:2166	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	7	65	theme	chain	1154:1158	arg1	acid					1166:1169	short chain fatty acid	1148:1169	short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1148:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	65	theme	chain	1154:1158	arg1	SCFA					1172:1175	SCFA	1172:1175	SCFA	1172:1175	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	2	66	theme	medicinal	340:348	arg1	herbs					350:354	medicinal herbs	340:354	medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine	340:470	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	5	67	theme	one-third	948:956	arg1	abundance					921:929	The relative abundance	908:929	The relative abundance of approximately one-third of the 243 enumerated species	908:986	The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs.
30889210	12	68	theme	functional	2110:2119	arg1	interactions					2121:2132	potential functional interactions	2100:2132	potential functional interactions among medicinal herb-induced taxa	2100:2166	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	11	69	theme	Co-occurrence	1899:1911	arg1	analyses					1921:1928	Co-occurrence network analyses	1899:1928	Co-occurrence network analyses	1899:1928	Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures.
30889210	7	70	theme	sugar	1126:1130	arg1	utilization					1132:1142	sugar utilization	1126:1142	sugar utilization	1126:1142	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	5	71	theme	relative	912:919	arg1	abundance					921:929	The relative abundance	908:929	The relative abundance of approximately one-third of the 243 enumerated species	908:986	The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs.
30889210	4	72	theme	Principal	750:758	arg1	analysis					771:778	Principal coordinate analysis	750:778	Principal coordinate analysis	750:778	Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential.
30889210	8	73	theme	sugar	1579:1583	arg1	substrates					1585:1594	amino acid and sugar substrates	1564:1594	substrates	1585:1594	Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species.
30889210	7	74	theme	taxa	1226:1229	arg1	genomes					1202:1208	the genomes	1198:1208	the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb	1198:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	75	theme	herb	1290:1293	arg1	analysis					1263:1270	monosaccharide composition analysis	1236:1270	monosaccharide composition analysis of each medicinal herb	1236:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	7	76	theme	restructuring	1438:1450	arg1	drivers					1416:1422	potential drivers	1406:1422	potential drivers of microbiota restructuring	1406:1450	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	12	77	theme	related	2028:2034	arg1	relationships					2051:2063	related culture growth relationships	2028:2063	related culture growth relationships	2028:2063	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	5	78	theme	enumerated	969:978	arg1	species					980:986	the 243 enumerated species	961:986	the 243 enumerated species	961:986	The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs.
30889210	0	79	theme	herbs	127:131	arg1	interactions					77:88	community metabolic interactions	57:88	community metabolic interactions	57:88	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	0	79	theme	herbs	127:131	arg1	potential					104:112	prebiotic potential	94:112	prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics	94:183	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	12	80	theme	growth	2044:2049	arg1	relationships					2051:2063	related culture growth relationships	2028:2063	related culture growth relationships	2028:2063	Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.
30889210	8	81	theme	fermentative	1617:1628	arg1	species					1630:1636	fermentative species	1617:1636	fermentative species	1617:1636	Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species.
30889210	11	82	theme	taxa	1959:1962	arg1	pairs					1964:1968	taxa pairs	1959:1968	taxa pairs	1959:1968	Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures.
30889210	0	83	theme	medicinal	117:125	arg1	herbs					127:131	medicinal herbs	117:131	medicinal herbs used in neurodegenerative disease and as nootropics	117:183	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	2	84	theme	other	434:438	arg1	systems					452:458	other traditional systems	434:458	other traditional systems	434:458	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	7	85	theme	monosaccharide	1236:1249	arg1	analysis					1263:1270	monosaccharide composition analysis	1236:1270	monosaccharide composition analysis of each medicinal herb	1236:1293	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	0	86	theme	rRNA	4:7	arg1	profiling					14:22	16S rRNA gene profiling	0:22	16S rRNA gene profiling	0:22	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	0	87	theme	neurodegenerative	141:157	arg1	disease					159:165	neurodegenerative disease	141:165	neurodegenerative disease	141:165	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	9	88	theme	amino	1677:1681	arg1	taxa					1653:1656	taxa	1653:1656	taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation	1653:1757	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	9	88	theme	amino	1677:1681	arg1	fermenters					1688:1697	efficient amino acid fermenters	1667:1697	efficient amino acid fermenters	1667:1697	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	7	89	theme	communities	1382:1392	arg1	interpretation					1344:1357	the interpretation	1340:1357	the interpretation of resulting microbial communities	1340:1392	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	3	90	theme	16S	687:689	arg1	sequencing					696:705	16S rRNA sequencing	687:705	16S rRNA sequencing	687:705	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa.
30889210	2	91	theme	traditional	440:450	arg1	systems					452:458	other traditional systems	434:458	other traditional systems	434:458	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
30889210	0	92	theme	genome	28:33	arg1	reconstruction					35:48	genome reconstruction	28:48	genome reconstruction	28:48	16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics.
30889210	1	93	theme	herbal	221:226	arg1	medicines					228:236	nervine herbal medicines	213:236	nervine herbal medicines	213:236	The prebiotic potential of nervine herbal medicines has been scarcely studied.
30889210	7	94	theme	resulting	1362:1370	arg1	communities					1382:1392	resulting microbial communities	1362:1392	resulting microbial communities	1362:1392	In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring.
30889210	10	95	theme	Herb-induced	1760:1771	arg1	communities					1783:1793	Herb-induced microbial communities	1760:1793	Herb-induced microbial communities	1760:1793	Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways.
30889210	3	96	theme	profound	716:723	arg1	changes					725:731	profound changes	716:731	profound changes in diverse taxa	716:747	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa.
30889210	4	97	theme	metabolic	887:895	arg1	potential					897:905	unique metabolic potential	880:905	unique metabolic potential	880:905	Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential.
30889210	4	98	theme	microbial	837:845	arg1	communities					847:857	unique microbial communities	830:857	unique microbial communities predicted to display unique metabolic potential	830:905	Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential.
30889210	3	99	theme	cultures	516:523	arg1	Profiling					497:505	Profiling	497:505	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing	497:705	Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa.
30889210	9	100	theme	amino	1725:1729	arg1	acid					1731:1734	amino acid	1725:1734	amino acid	1725:1734	We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation.
30889210	2	101	theme	neurological	386:397	arg1	health					399:404	neurological health	386:404	neurological health	386:404	We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota.
31063846	16	0	theme	related	2278:2284	arg1	modules					2270:2276	the increased modules	2256:2276	the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients	2256:2346	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	4	1	theme	healthy	798:804	arg1	HC					816:817	HC	816:817	HC	816:817	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	1	theme	healthy	798:804	arg1	controls					806:813	the normal cognition healthy controls	777:813	the normal cognition healthy controls (HC)	777:818	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	14	2	theme	aMCI	2058:2061	arg1	patients					2070:2077	aMCI and AD patients	2058:2077	patients	2070:2077	And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients.
31063846	15	3	theme	severity	2149:2156	arg1	scores					2158:2163	the clinical severity scores	2136:2163	the clinical severity scores of AD patients	2136:2178	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	16	4	theme	glycan	2289:2294	arg1	biosynthesis					2296:2307	glycan biosynthesis	2289:2307	glycan biosynthesis	2289:2307	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	19	5	theme	stage	2903:2907	arg1	aMCI					2909:2912	predementia stage aMCI	2891:2912	predementia stage aMCI	2891:2912	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	12	6	dep	reduced	1731:1737	arg1	P = 0.008					1740:1748	P = 0.008	1740:1748	P = 0.008	1740:1748	Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC.
31063846	12	6	dep	reduced	1731:1737	arg1	whereas					1752:1758	whereas	1752:1758	whereas	1752:1758	Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC.
31063846	19	7	theme	healthy	2918:2924	arg1	subjects					2926:2933	healthy subjects	2918:2933	healthy subjects	2918:2933	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	17	8	from	aMCI	2586:2589	arg1	AD					2578:2579	AD	2578:2579	AD	2578:2579	Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925).
31063846	17	9	theme	predominant	2460:2470	arg1	microbiota					2472:2481	predominant microbiota	2460:2481	predominant microbiota	2460:2481	Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925).
31063846	2	10	theme	animal	357:362	arg1	studies					364:370	several animal studies	349:370	several animal studies	349:370	Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD.
31063846	9	11	theme	Montreal	1316:1323	arg1	MoCA					1347:1350	MoCA	1347:1350	MoCA	1347:1350	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	11	theme	Montreal	1316:1323	arg1	Assessment					1335:1344	Montreal Cognitive Assessment	1316:1344	Montreal Cognitive Assessment (MoCA)	1316:1351	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	4	12	theme	normal	781:786	arg1	HC					816:817	HC	816:817	HC	816:817	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	12	theme	normal	781:786	arg1	controls					806:813	the normal cognition healthy controls	777:813	the normal cognition healthy controls (HC)	777:818	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	8	13	theme	Phylogenetic	1122:1133	arg1	Investigation					1135:1147	Phylogenetic Investigation	1122:1147	Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)	1122:1211	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	14	14	theme	progressive	2015:2025	arg1	prevalence					2036:2045	a progressive enriched prevalence	2013:2045	a progressive enriched prevalence from HC to aMCI and AD patients	2013:2077	And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients.
31063846	9	15	used	used	1399:1402	arg2	MoCA					1347:1350	MoCA	1347:1350	MoCA	1347:1350	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	15	used	used	1399:1402	arg2	MMSE					1309:1312	MMSE	1309:1312	MMSE	1309:1312	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	15	used	used	1399:1402	arg2	scores					1387:1392	Clinical Dementia Rating (CDR) scores	1356:1392	Clinical Dementia Rating (CDR) scores	1356:1392	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	15	used	used	1399:1402	arg2	Assessment					1335:1344	Montreal Cognitive Assessment	1316:1344	Montreal Cognitive Assessment (MoCA)	1316:1351	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	15	used	used	1399:1402	arg2	Examination					1296:1306	The Mini-Mental State Examination	1274:1306	The Mini-Mental State Examination (MMSE)	1274:1313	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	11	16	theme	control	1639:1645	arg1	groups					1647:1652	healthy control groups	1631:1652	healthy control groups	1631:1652	And the microbial composition was distinct among aMCI, AD and healthy control groups.
31063846	13	17	theme	phyla	1933:1937	arg1	levels					1913:1918	the order, class and family levels	1885:1918	the order, class and family levels of these two phyla	1885:1937	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	0	18	from	impairment	81:90	arg1	cohort					116:121	a Chinese cohort	106:121	a Chinese cohort	106:121	Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
31063846	10	19	theme	microbial	1484:1492	arg1	diversity					1494:1502	The fecal microbial diversity	1474:1502	The fecal microbial diversity	1474:1502	RESULTS The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC.
31063846	15	20	theme	altered	2201:2207	arg1	microbiomes					2209:2219	altered microbiomes	2201:2219	altered microbiomes	2201:2219	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	17	21	theme	discriminating	2429:2442	arg1	models					2444:2449	the discriminating models	2425:2449	the discriminating models based on predominant microbiota	2425:2481	Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925).
31063846	4	22	with	patients	689:696	arg1	AD					703:704	AD	703:704	AD	703:704	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	9	23	theme	Dementia	1365:1372	arg1	scores					1387:1392	Clinical Dementia Rating (CDR) scores	1356:1392	Clinical Dementia Rating (CDR) scores	1356:1392	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	8	24	theme	States	1196:1201	arg1	Reconstruction					1167:1180	Reconstruction	1167:1180	Reconstruction of Unobserved States (PICRUSt)	1167:1211	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	9	25	from	severity	1420:1427	arg1	patients					1456:1463	patients	1456:1463	patients	1456:1463	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	4	26	dep	patients	689:696	arg1	impairment					747:756	Pre-onset stage amnestic mild cognitive impairment	707:756	Pre-onset stage amnestic mild cognitive impairment	707:756	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	26	dep	patients	689:696	arg1	patients					689:696	patients	689:696	patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD)	689:771	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	26	dep	patients	689:696	arg1	aMCI					759:762	aMCI	759:762	aMCI	759:762	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	26	dep	patients	689:696	arg1	AD					769:770	AD	769:770	AD	769:770	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	0	27	from	health	96:101	arg1	cohort					116:121	a Chinese cohort	106:121	a Chinese cohort	106:121	Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
31063846	10	28	theme	aMCI	1547:1550	arg1	patients					1552:1559	aMCI patients	1547:1559	aMCI patients	1547:1559	RESULTS The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC.
31063846	4	29	with	controls	806:813	arg1	AD					703:704	AD	703:704	AD	703:704	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	0	30	theme	mild	66:69	arg1	impairment					81:90	amnestic mild cognitive impairment	57:90	amnestic mild cognitive impairment	57:90	Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
31063846	1	31	theme	disability	301:310	arg1	causes					291:296	the main causes	282:296	the main causes of disability in elder people worldwide	282:336	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	3	32	theme	whole	563:567	arg1	process					569:575	the whole process	559:575	the whole process of AD	559:581	However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD.
31063846	2	33	theme	AD	454:455	arg1	deposition					440:449	the amyloid deposition	428:449	the amyloid deposition of AD	428:455	Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD.
31063846	7	34	theme	Miseq	1091:1095	arg1	sequencing					1097:1106	ribosomal RNA Miseq sequencing	1077:1106	ribosomal RNA Miseq sequencing	1077:1106	The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing.
31063846	1	35	theme	elder	315:319	arg1	worldwide					328:336	elder people worldwide	315:336	elder people worldwide	315:336	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	6	36	dep	METHODS	922:928	arg1	total					932:936	A total	930:936	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC)	922:979	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study.
31063846	1	37	dep	OBJECTIVE	124:132	arg1	one					275:277	one	275:277	one	275:277	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	1	37	dep	OBJECTIVE	124:132	arg1	causes					291:296	the main causes	282:296	the main causes of disability in elder people worldwide	282:336	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	5	38	theme	clinical	876:883	arg1	characteristics					885:899	IM and clinical characteristics	869:899	IM and clinical characteristics of AD	869:905	Additionally, the potential association between IM and clinical characteristics of AD was evaluated.
31063846	7	39	theme	ribosomal	1077:1085	arg1	sequencing					1097:1106	ribosomal RNA Miseq sequencing	1077:1106	ribosomal RNA Miseq sequencing	1077:1106	The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing.
31063846	14	40	from	HC	2052:2053	arg1	prevalence					2036:2045	a progressive enriched prevalence	2013:2045	a progressive enriched prevalence from HC to aMCI and AD patients	2013:2077	And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients.
31063846	4	41	theme	amnestic	723:730	arg1	impairment					747:756	Pre-onset stage amnestic mild cognitive impairment	707:756	Pre-onset stage amnestic mild cognitive impairment	707:756	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	41	theme	amnestic	723:730	arg1	patients					689:696	patients	689:696	patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD)	689:771	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	10	42	theme	AD	1521:1522	arg1	patients					1524:1531	AD patients	1521:1531	AD patients	1521:1531	RESULTS The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC.
31063846	16	43	theme	immune	2382:2387	arg1	system					2389:2394	immune system	2382:2394	immune system in AD patients	2382:2409	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	19	44	theme	microbial	2771:2779	arg1	communities					2781:2791	Distinct microbial communities	2762:2791	Distinct microbial communities	2762:2791	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	20	45	theme	new	3015:3017	arg1	target					3031:3036	new therapeutic target	3015:3036	new therapeutic target for intervention or a marker for this disease	3015:3082	These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.
31063846	8	46	used	used	1217:1220	arg2	Investigation					1135:1147	Phylogenetic Investigation	1122:1147	Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)	1122:1211	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	0	47	theme	Altered	0:6	arg1	microbiomes					8:18	Altered microbiomes	0:18	Altered microbiomes	0:18	Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
31063846	5	48	theme	IM	869:870	arg1	characteristics					885:899	IM and clinical characteristics	869:899	IM and clinical characteristics of AD	869:905	Additionally, the potential association between IM and clinical characteristics of AD was evaluated.
31063846	19	49	dep	CONCLUSIONS	2750:2760	arg1	communities					2781:2791	Distinct microbial communities	2762:2791	Distinct microbial communities	2762:2791	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	8	50	theme	microbiota	1262:1271	arg1	shift					1242:1246	function shift	1233:1246	function shift of intestinal microbiota	1233:1271	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	2	51	theme	gut-brain	392:400	arg1	axis					403:406	the 'gut-brain' axis	387:406	the 'gut-brain' axis	387:406	Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD.
31063846	7	52	theme	bacterial	1033:1041	arg1	communities					1043:1053	gut bacterial communities	1029:1053	gut bacterial communities	1029:1053	The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing.
31063846	15	53	theme	significant	2091:2101	arg1	correlation					2103:2113	a significant correlation	2089:2113	a significant correlation	2089:2113	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	16	54	theme	aMCI	2334:2337	arg1	patients					2339:2346	AD and aMCI patients	2327:2346	patients	2339:2346	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	9	55	theme	impairment	1442:1451	arg1	severity					1420:1427	the severity	1416:1427	the severity of cognitive impairment in patients	1416:1463	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	19	56	theme	enriched	2805:2812	arg1	CONCLUSIONS					2750:2760	CONCLUSIONS	2750:2760	CONCLUSIONS	2750:2760	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	19	56	theme	enriched	2805:2812	arg1	Enterobacteriaceae					2814:2831	especially enriched Enterobacteriaceae	2794:2831	especially enriched Enterobacteriaceae	2794:2831	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	12	57	from	AD	1814:1815	arg1	enriched					1798:1805	enriched	1798:1805	enriched	1798:1805	Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC.
31063846	13	58	theme	similar	1848:1854	arg1	alterations					1856:1866	similar alterations	1848:1866	similar alterations	1848:1866	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	1	59	theme	causes	291:296	arg1	one					275:277	one	275:277	one	275:277	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	1	59	theme	causes	291:296	arg1	causes					291:296	the main causes	282:296	the main causes of disability in elder people worldwide	282:336	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	4	60	theme	cognitive	737:745	arg1	impairment					747:756	Pre-onset stage amnestic mild cognitive impairment	707:756	Pre-onset stage amnestic mild cognitive impairment	707:756	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	60	theme	cognitive	737:745	arg1	patients					689:696	patients	689:696	patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD)	689:771	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	16	61	theme	KEGG	2236:2239	arg1	results					2241:2247	the KEGG results	2232:2247	the KEGG results	2232:2247	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	15	62	theme	AD	2168:2169	arg1	patients					2171:2178	AD patients	2168:2178	AD patients	2168:2178	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	12	63	theme	phylum	1695:1700	arg1	Firmicutes					1702:1711	phylum Firmicutes	1695:1711	phylum Firmicutes	1695:1711	Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC.
31063846	9	64	theme	Mini-Mental	1278:1288	arg1	MMSE					1309:1312	MMSE	1309:1312	MMSE	1309:1312	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	64	theme	Mini-Mental	1278:1288	arg1	Examination					1296:1306	The Mini-Mental State Examination	1274:1306	The Mini-Mental State Examination (MMSE)	1274:1313	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	16	65	from	metabolism	2313:2322	arg1	patients					2339:2346	AD and aMCI patients	2327:2346	patients	2339:2346	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	1	66	from	causes	291:296	arg1	worldwide					328:336	elder people worldwide	315:336	elder people worldwide	315:336	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	16	67	theme	increased	2260:2268	arg1	modules					2270:2276	the increased modules	2256:2276	the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients	2256:2346	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	15	68	theme	clinical	2140:2147	arg1	scores					2158:2163	the clinical severity scores	2136:2163	the clinical severity scores of AD patients	2136:2178	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	18	69	theme	Enterobacteriaceae	2659:2676	arg1	abundance					2639:2647	the abundance	2635:2647	the abundance of family Enterobacteriaceae	2635:2676	Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698).
31063846	4	70	theme	cognition	788:796	arg1	HC					816:817	HC	816:817	HC	816:817	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	70	theme	cognition	788:796	arg1	controls					806:813	the normal cognition healthy controls	777:813	the normal cognition healthy controls (HC)	777:818	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	17	71	dep	HC	2530:2531	arg1	0.940					2547:2551	0.940	2547:2551	0.940	2547:2551	Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925).
31063846	17	71	dep	HC	2530:2531	arg1	AUC = 0.890					2534:2544	AUC = 0.890	2534:2544	AUC = 0.890	2534:2544	Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925).
31063846	3	72	theme	human	495:499	arg1	AD					501:502	human AD	495:502	human AD	495:502	However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD.
31063846	1	73	theme	cognitive	250:258	arg1	impairment					260:269	cognitive impairment	250:269	cognitive impairment	250:269	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	20	74	theme	therapeutic	3019:3029	arg1	target					3031:3036	new therapeutic target	3015:3036	new therapeutic target for intervention or a marker for this disease	3015:3082	These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.
31063846	19	75	with	patients	2855:2862	arg1	AD					2869:2870	AD	2869:2870	AD	2869:2870	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	16	76	theme	AD	2327:2328	arg1	patients					2339:2346	AD and aMCI patients	2327:2346	patients	2339:2346	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	4	77	theme	prospective	592:602	arg1	study					624:628	this prospective and cross-sectional study	587:628	this prospective and cross-sectional study	587:628	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	14	78	theme	enriched	2027:2034	arg1	prevalence					2036:2045	a progressive enriched prevalence	2013:2045	a progressive enriched prevalence from HC to aMCI and AD patients	2013:2077	And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients.
31063846	10	79	dep	RESULTS	1466:1472	arg1	decreased					1508:1516	decreased	1508:1516	was decreased in AD patients compared with aMCI patients and HC	1504:1566	RESULTS The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC.
31063846	9	80	theme	Cognitive	1325:1333	arg1	MoCA					1347:1350	MoCA	1347:1350	MoCA	1347:1350	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	80	theme	Cognitive	1325:1333	arg1	Assessment					1335:1344	Montreal Cognitive Assessment	1316:1344	Montreal Cognitive Assessment (MoCA)	1316:1351	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	18	81	theme	family	2652:2657	arg1	Enterobacteriaceae					2659:2676	family Enterobacteriaceae	2652:2676	family Enterobacteriaceae	2652:2676	Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698).
31063846	4	82	theme	cross-sectional	608:622	arg1	study					624:628	this prospective and cross-sectional study	587:628	this prospective and cross-sectional study	587:628	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	13	83	located	observed	1873:1880	arg1	levels					1913:1918	the order, class and family levels	1885:1918	the order, class and family levels of these two phyla	1885:1937	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	13	83	located	observed	1873:1880	arg1	addition					1838:1845	addition	1838:1845	addition	1838:1845	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	13	83	located	observed	1873:1880	arg2	alterations					1856:1866	similar alterations	1848:1866	similar alterations	1848:1866	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	16	84	from	biosynthesis	2296:2307	arg1	patients					2339:2346	AD and aMCI patients	2327:2346	patients	2339:2346	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	20	85	theme	novel	2942:2946	arg1	findings					2948:2955	These novel findings	2936:2955	These novel findings	2936:2955	These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.
31063846	16	86	from	system	2389:2394	arg1	patients					2402:2409	AD patients	2399:2409	AD patients	2399:2409	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	3	87	dep	process	569:575	arg1	including					549:557	including	549:557	including	549:557	However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD.
31063846	8	88	theme	Communities	1152:1162	arg1	Investigation					1135:1147	Phylogenetic Investigation	1122:1147	Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)	1122:1211	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	10	89	theme	fecal	1478:1482	arg1	diversity					1494:1502	The fecal microbial diversity	1474:1502	The fecal microbial diversity	1474:1502	RESULTS The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC.
31063846	15	90	theme	microbiomes	2209:2219	arg1	abundance					2188:2196	the abundance	2184:2196	the abundance of altered microbiomes	2184:2219	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	15	90	theme	microbiomes	2209:2219	arg1	scores					2158:2163	the clinical severity scores	2136:2163	the clinical severity scores of AD patients	2136:2178	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	9	91	theme	Clinical	1356:1363	arg1	scores					1387:1392	Clinical Dementia Rating (CDR) scores	1356:1392	Clinical Dementia Rating (CDR) scores	1356:1392	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	13	92	theme	family	1906:1911	arg1	levels					1913:1918	the order, class and family levels	1885:1918	the order, class and family levels of these two phyla	1885:1937	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	20	93	theme	new	2967:2969	arg1	clues					2971:2975	new clues	2967:2975	new clues	2967:2975	These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.
31063846	9	94	theme	Rating	1374:1379	arg1	scores					1387:1392	Clinical Dementia Rating (CDR) scores	1356:1392	Clinical Dementia Rating (CDR) scores	1356:1392	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	95	from	impairment	1442:1451	arg1	patients					1456:1463	patients	1456:1463	patients	1456:1463	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	6	96	theme	subjects	944:951	arg1	total					932:936	A total	930:936	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC)	922:979	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study.
31063846	4	97	theme	Pre-onset	707:715	arg1	impairment					747:756	Pre-onset stage amnestic mild cognitive impairment	707:756	Pre-onset stage amnestic mild cognitive impairment	707:756	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	97	theme	Pre-onset	707:715	arg1	patients					689:696	patients	689:696	patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD)	689:771	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	8	98	theme	Unobserved	1185:1194	arg1	PICRUSt					1204:1210	PICRUSt	1204:1210	PICRUSt	1204:1210	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	8	98	theme	Unobserved	1185:1194	arg1	States					1196:1201	Unobserved States	1185:1201	Unobserved States (PICRUSt)	1185:1211	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	0	99	theme	cognitive	71:79	arg1	impairment					81:90	amnestic mild cognitive impairment	57:90	amnestic mild cognitive impairment	57:90	Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
31063846	9	100	theme	CDR	1382:1384	arg1	scores					1387:1392	Clinical Dementia Rating (CDR) scores	1356:1392	Clinical Dementia Rating (CDR) scores	1356:1392	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	16	101	theme	AD	2399:2400	arg1	patients					2402:2409	AD patients	2399:2409	AD patients	2399:2409	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	3	102	from	dysbiosis	482:490	arg1	AD					501:502	human AD	495:502	human AD	495:502	However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD.
31063846	7	103	theme	RNA	1087:1089	arg1	sequencing					1097:1106	ribosomal RNA Miseq sequencing	1077:1106	ribosomal RNA Miseq sequencing	1077:1106	The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing.
31063846	13	104	theme	class	1896:1900	arg1	levels					1913:1918	the order, class and family levels	1885:1918	the order, class and family levels of these two phyla	1885:1937	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	19	105	theme	Distinct	2762:2769	arg1	communities					2781:2791	Distinct microbial communities	2762:2791	Distinct microbial communities	2762:2791	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	11	106	theme	healthy	1631:1637	arg1	groups					1647:1652	healthy control groups	1631:1652	healthy control groups	1631:1652	And the microbial composition was distinct among aMCI, AD and healthy control groups.
31063846	1	107	theme	people	321:326	arg1	worldwide					328:336	elder people worldwide	315:336	elder people worldwide	315:336	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	0	108	theme	Chinese	108:114	arg1	cohort					116:121	a Chinese cohort	106:121	a Chinese cohort	106:121	Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
31063846	5	109	theme	AD	904:905	arg1	characteristics					885:899	IM and clinical characteristics	869:899	IM and clinical characteristics of AD	869:905	Additionally, the potential association between IM and clinical characteristics of AD was evaluated.
31063846	5	110	theme	potential	839:847	arg1	association					849:859	the potential association	835:859	the potential association between IM and clinical characteristics of AD	835:905	Additionally, the potential association between IM and clinical characteristics of AD was evaluated.
31063846	6	111	dep	subjects	944:951	arg1	AD					957:958	33 AD	954:958	33 AD	954:958	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study.
31063846	6	111	dep	subjects	944:951	arg1	aMCI					964:967	32 aMCI	961:967	32 aMCI	961:967	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study.
31063846	6	111	dep	subjects	944:951	arg1	HC					977:978	32 HC	974:978	32 HC	974:978	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study.
31063846	6	111	dep	subjects	944:951	arg1	subjects					944:951	97 subjects	941:951	97 subjects (33 AD, 32 aMCI, and 32 HC)	941:979	METHODS A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study.
31063846	4	112	theme	stage	717:721	arg1	impairment					747:756	Pre-onset stage amnestic mild cognitive impairment	707:756	Pre-onset stage amnestic mild cognitive impairment	707:756	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	112	theme	stage	717:721	arg1	patients					689:696	patients	689:696	patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD)	689:771	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	7	113	theme	communities	1043:1053	arg1	composition					1014:1024	The composition	1010:1024	The composition of gut bacterial communities	1010:1053	The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing.
31063846	13	114	theme	order	1889:1893	arg1	levels					1913:1918	the order, class and family levels	1885:1918	the order, class and family levels of these two phyla	1885:1937	In addition, similar alterations were observed at the order, class and family levels of these two phyla.
31063846	2	115	theme	several	349:355	arg1	studies					364:370	several animal studies	349:370	several animal studies	349:370	Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD.
31063846	7	116	theme	gut	1029:1031	arg1	communities					1043:1053	gut bacterial communities	1029:1053	gut bacterial communities	1029:1053	The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing.
31063846	9	117	theme	cognitive	1432:1440	arg1	impairment					1442:1451	cognitive impairment	1432:1451	cognitive impairment in patients	1432:1463	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	8	118	theme	function	1233:1240	arg1	shift					1242:1246	function shift	1233:1246	function shift of intestinal microbiota	1233:1271	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	8	119	theme	intestinal	1251:1260	arg1	microbiota					1262:1271	intestinal microbiota	1251:1271	intestinal microbiota	1251:1271	In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota.
31063846	9	120	from	patients	1456:1463	arg1	severity					1420:1427	the severity	1416:1427	the severity of cognitive impairment in patients	1416:1463	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	2	121	theme	amyloid	432:438	arg1	deposition					440:449	the amyloid deposition	428:449	the amyloid deposition of AD	428:455	Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD.
31063846	3	122	theme	AD	580:581	arg1	process					569:575	the whole process	559:575	the whole process of AD	559:581	However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD.
31063846	1	123	theme	progressive	206:216	arg1	condition					236:244	the progressive neurodegenerative condition	202:244	the progressive neurodegenerative condition	202:244	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	0	124	theme	amnestic	57:64	arg1	impairment					81:90	amnestic mild cognitive impairment	57:90	amnestic mild cognitive impairment	57:90	Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort.
31063846	1	125	theme	main	286:289	arg1	causes					291:296	the main causes	282:296	the main causes of disability in elder people worldwide	282:336	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	12	126	theme	bacterial	1661:1669	arg1	taxa					1671:1674	bacterial taxa	1661:1674	bacterial taxa	1661:1674	Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC.
31063846	11	127	theme	microbial	1577:1585	arg1	distinct					1603:1610	distinct	1603:1610	distinct	1603:1610	And the microbial composition was distinct among aMCI, AD and healthy control groups.
31063846	11	127	theme	microbial	1577:1585	arg1	composition					1587:1597	the microbial composition	1573:1597	the microbial composition	1573:1597	And the microbial composition was distinct among aMCI, AD and healthy control groups.
31063846	12	128	theme	Firmicutes	1702:1711	arg1	proportion					1681:1690	the proportion	1677:1690	the proportion of phylum Firmicutes	1677:1711	Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC.
31063846	12	129	from	enriched	1798:1805	arg1	AD					1814:1815	the AD	1810:1815	the AD	1810:1815	Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC.
31063846	4	130	theme	mild	732:735	arg1	impairment					747:756	Pre-onset stage amnestic mild cognitive impairment	707:756	Pre-onset stage amnestic mild cognitive impairment	707:756	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	130	theme	mild	732:735	arg1	patients					689:696	patients	689:696	patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD)	689:771	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	4	131	from	differences	655:665	arg1	microbiome					670:679	microbiome	670:679	microbiome	670:679	In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC).
31063846	15	132	theme	patients	2171:2178	arg1	abundance					2188:2196	the abundance	2184:2196	the abundance of altered microbiomes	2184:2219	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	15	132	theme	patients	2171:2178	arg1	scores					2158:2163	the clinical severity scores	2136:2163	the clinical severity scores of AD patients	2136:2178	Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes.
31063846	16	133	theme	related	2371:2377	arg1	pathways					2362:2369	pathways	2362:2369	pathways related to immune system in AD patients	2362:2409	Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients.
31063846	14	134	theme	AD	2067:2068	arg1	patients					2070:2077	aMCI and AD patients	2058:2077	patients	2070:2077	And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients.
31063846	1	135	theme	neurodegenerative	218:234	arg1	condition					236:244	the progressive neurodegenerative condition	202:244	the progressive neurodegenerative condition	202:244	OBJECTIVE (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide.
31063846	19	136	theme	predementia	2891:2901	arg1	aMCI					2909:2912	predementia stage aMCI	2891:2912	predementia stage aMCI	2891:2912	CONCLUSIONS Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects.
31063846	3	137	theme	gut	478:480	arg1	dysbiosis					482:490	gut dysbiosis	478:490	gut dysbiosis in human AD	478:502	However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD.
31063846	9	138	theme	State	1290:1294	arg1	MMSE					1309:1312	MMSE	1309:1312	MMSE	1309:1312	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
31063846	9	138	theme	State	1290:1294	arg1	Examination					1296:1306	The Mini-Mental State Examination	1274:1306	The Mini-Mental State Examination (MMSE)	1274:1313	The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients.
30872163	1	0	link	asparagine-linked	87:103	arg1	ALG13					80:84	ALG13	80:84	ALG13 (asparagine-linked glycosylation 13 homolog)	80:129	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	1	0	link	asparagine-linked	87:103	arg1	homolog					122:128	asparagine-linked glycosylation 13 homolog	87:128	asparagine-linked glycosylation 13 homolog	87:128	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	4	1	from	expression	620:629	arg1	CNS					671:673	CNS	671:673	CNS	671:673	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	4	1	from	expression	620:629	arg1	system					663:668	the central nervous system	643:668	the central nervous system (CNS) had histologically	643:693	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	4	1	from	expression	620:629	arg1	specificity					708:718	cellular specificity	699:718	cellular specificity	699:718	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	5	2	from	levels	871:876	arg1	forebrain					911:919	the forebrain	907:919	the forebrain of wild-type (WT) mice	907:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	4	3	theme	cellular	699:706	arg1	specificity					708:718	cellular specificity	699:718	cellular specificity	699:718	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	9	4	theme	association	1552:1562	arg1	report					1516:1521	this report	1511:1521	this report	1511:1521	To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
30872163	9	4	theme	association	1552:1562	arg1	evidence					1536:1543	the first evidence	1526:1543	the first evidence of the association between ALG13 and epilepsy in experimental animals	1526:1613	To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
30872163	1	5	theme	important	261:269	arg1	factor					276:281	an important risk factor	258:281	an important risk factor that leads to neurological deficits and disorders	258:331	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	9	6	from	ALG13	1572:1576	arg1	animals					1607:1613	experimental animals	1594:1613	experimental animals	1594:1613	To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
30872163	1	7	link	N-linked	221:228	arg1	glycosylation					230:242	abnormal N-linked glycosylation	212:242	abnormal N-linked glycosylation	212:242	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	5	8	from	protein	896:902	arg1	forebrain					911:919	the forebrain	907:919	the forebrain of wild-type (WT) mice	907:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	4	9	dep	cortex	750:755	arg1	the					746:748	the	746:748	the	746:748	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	8	10	theme	signaling	1414:1422	arg1	pathways					1424:1431	hyperactive mTOR signaling pathways	1397:1431	hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice	1397:1478	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	1	11	theme	risk	271:274	arg1	factor					276:281	an important risk factor	258:281	an important risk factor that leads to neurological deficits and disorders	258:331	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	6	12	theme	increased	1092:1100	arg1	rates					1112:1116	strikingly increased mortality rates	1081:1116	strikingly increased mortality rates	1081:1116	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	7	13	from	mice	1290:1293	arg1	exacerbated					1266:1276	exacerbated	1266:1276	exacerbated	1266:1276	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	7	14	from	exacerbated	1266:1276	arg1	mice					1290:1293	Alg13 KO mice	1281:1293	Alg13 KO mice	1281:1293	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	8	15	theme	epilepsy	1377:1384	arg1	mechanisms					1348:1357	the possible mechanisms	1335:1357	the possible mechanisms of ALG13-involved epilepsy	1335:1384	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	5	16	theme	mice	939:942	arg1	forebrain					911:919	the forebrain	907:919	the forebrain of wild-type (WT) mice	907:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	1	17	theme	asparagine-linked	87:103	arg1	ALG13					80:84	ALG13	80:84	ALG13 (asparagine-linked glycosylation 13 homolog)	80:129	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	1	17	theme	asparagine-linked	87:103	arg1	homolog					122:128	asparagine-linked glycosylation 13 homolog	87:128	asparagine-linked glycosylation 13 homolog	87:128	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	9	18	theme	experimental	1594:1605	arg1	animals					1607:1613	experimental animals	1594:1613	experimental animals	1594:1613	To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
30872163	5	19	dep	wild-type	924:932	arg1	WT					935:936	WT	935:936	WT	935:936	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	5	20	from	mRNA	887:890	arg1	forebrain					911:919	the forebrain	907:919	the forebrain of wild-type (WT) mice	907:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	5	21	theme	protein	896:902	arg1	levels					871:876	the expression levels	856:876	the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice	856:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	4	22	theme	nervous	655:661	arg1	CNS					671:673	CNS	671:673	CNS	671:673	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	4	22	theme	nervous	655:661	arg1	system					663:668	the central nervous system	643:668	the central nervous system (CNS) had histologically	643:693	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	7	23	theme	KA-induced	1185:1194	arg1	changes					1226:1232	KA-induced epilepsy-related pathological changes	1185:1232	KA-induced epilepsy-related pathological changes of the brain	1185:1245	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	1	24	link	N-linked	184:191	arg1	glycosylation					193:205	N-linked glycosylation	184:205	N-linked glycosylation	184:205	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	8	25	dep	cortex	1440:1445	arg1	the					1436:1438	the	1436:1438	the	1436:1438	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	6	26	theme	electrographic	1056:1069	arg1	seizures					1071:1078	prolonged electrographic seizures	1046:1078	prolonged electrographic seizures	1046:1078	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	5	27	theme	expression	860:869	arg1	levels					871:876	the expression levels	856:876	the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice	856:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	7	28	theme	epilepsy-related	1196:1211	arg1	changes					1226:1232	KA-induced epilepsy-related pathological changes	1185:1232	KA-induced epilepsy-related pathological changes of the brain	1185:1245	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	6	29	theme	epileptic	1152:1160	arg1	seizures					1162:1169	epileptic seizures	1152:1169	epileptic seizures	1152:1169	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	7	30	theme	Alg13	1281:1285	arg1	mice					1290:1293	Alg13 KO mice	1281:1293	Alg13 KO mice	1281:1293	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	3	31	theme	seizures	583:590	arg1	susceptibility					539:552	increased susceptibility	529:552	increased susceptibility to	529:555	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	3	31	theme	seizures	583:590	arg1	severity					561:568	severity	561:568	severity of epileptic seizures	561:590	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	1	32	theme	N-linked	184:191	arg1	glycosylation					193:205	N-linked glycosylation	184:205	N-linked glycosylation	184:205	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	0	33	theme	ALG13	0:4	arg1	Deficiency					6:15	ALG13 Deficiency	0:15	ALG13 Deficiency	0:15	ALG13 Deficiency Associated with Increased Seizure Susceptibility and Severity.
30872163	4	34	from	neurons	735:741	arg1	hippocampus					761:771	hippocampus	761:771	hippocampus	761:771	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	4	34	from	neurons	735:741	arg1	cortex					750:755	cortex	750:755	cortex	750:755	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	1	35	theme	glycosylation	105:117	arg1	ALG13					80:84	ALG13	80:84	ALG13 (asparagine-linked glycosylation 13 homolog)	80:129	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	1	35	theme	glycosylation	105:117	arg1	homolog					122:128	asparagine-linked glycosylation 13 homolog	87:128	asparagine-linked glycosylation 13 homolog	87:128	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	1	36	theme	glycosylation	193:205	arg1	process					173:179	the process	169:179	the process of N-linked glycosylation	169:205	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	6	37	theme	epileptic	956:964	arg1	progressions					966:977	KA-induced epileptic progressions	945:977	KA-induced epileptic progressions	945:977	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	38	theme	KA-induced	945:954	arg1	progressions					966:977	KA-induced epileptic progressions	945:977	KA-induced epileptic progressions	945:977	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	5	39	theme	wild-type	924:932	arg1	mice					939:942	wild-type (WT) mice	924:942	wild-type (WT) mice	924:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	6	40	theme	responses	1139:1147	arg1	rates					1112:1116	strikingly increased mortality rates	1081:1116	strikingly increased mortality rates	1081:1116	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	40	theme	responses	1139:1147	arg1	seizures					1071:1078	prolonged electrographic seizures	1046:1078	prolonged electrographic seizures	1046:1078	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	40	theme	responses	1139:1147	arg1	severity					1127:1134	the severity	1123:1134	the severity of responses to epileptic seizures	1123:1169	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	3	41	theme	mouse	467:471	arg1	model					473:477	a kainic acid (KA)-induced epileptic mouse model	430:477	a kainic acid (KA)-induced epileptic mouse model	430:477	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	5	42	theme	KA-induced	813:822	arg1	seizures					824:831	KA-induced seizures	813:831	KA-induced seizures	813:831	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	1	43	theme	neurological	297:308	arg1	deficits					310:317	neurological deficits	297:317	neurological deficits	297:317	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	3	44	theme	epileptic	573:581	arg1	seizures					583:590	epileptic seizures	573:590	epileptic seizures	573:590	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	8	45	theme	possible	1339:1346	arg1	mechanisms					1348:1357	the possible mechanisms	1335:1357	the possible mechanisms of ALG13-involved epilepsy	1335:1384	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	0	46	theme	Seizure	43:49	arg1	Susceptibility					51:64	Increased Seizure Susceptibility	33:64	Increased Seizure Susceptibility	33:64	ALG13 Deficiency Associated with Increased Seizure Susceptibility and Severity.
30872163	2	47	theme	causal	347:352	arg1	relationship					354:365	the causal relationship	343:365	the causal relationship between ALG13 and epilepsy	343:392	However, the causal relationship between ALG13 and epilepsy remains unknown.
30872163	3	48	theme	-induced	448:455	arg1	model					473:477	a kainic acid (KA)-induced epileptic mouse model	430:477	a kainic acid (KA)-induced epileptic mouse model	430:477	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	4	49	theme	central	647:653	arg1	CNS					671:673	CNS	671:673	CNS	671:673	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	4	49	theme	central	647:653	arg1	system					663:668	the central nervous system	643:668	the central nervous system (CNS) had histologically	643:693	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	5	50	theme	ALG13	881:885	arg1	mRNA					887:890	ALG13 mRNA	881:890	ALG13 mRNA	881:890	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	1	51	theme	abnormal	212:219	arg1	glycosylation					230:242	abnormal N-linked glycosylation	212:242	abnormal N-linked glycosylation	212:242	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	0	52	theme	Increased	33:41	arg1	Susceptibility					51:64	Increased Seizure Susceptibility	33:64	Increased Seizure Susceptibility	33:64	ALG13 Deficiency Associated with Increased Seizure Susceptibility and Severity.
30872163	6	53	theme	knockout	1016:1023	arg1	rates					1112:1116	strikingly increased mortality rates	1081:1116	strikingly increased mortality rates	1081:1116	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	53	theme	knockout	1016:1023	arg1	seizures					1071:1078	prolonged electrographic seizures	1046:1078	prolonged electrographic seizures	1046:1078	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	53	theme	knockout	1016:1023	arg1	mice					1030:1033	Alg13 knockout (KO) mice	1010:1033	Alg13 knockout (KO) mice	1010:1033	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	53	theme	knockout	1016:1023	arg1	severity					1127:1134	the severity	1123:1134	the severity of responses to epileptic seizures	1123:1169	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	1	54	theme	N-linked	221:228	arg1	glycosylation					230:242	abnormal N-linked glycosylation	212:242	abnormal N-linked glycosylation	212:242	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	7	55	theme	pathological	1213:1224	arg1	changes					1226:1232	KA-induced epilepsy-related pathological changes	1185:1232	KA-induced epilepsy-related pathological changes of the brain	1185:1245	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	8	56	theme	mTOR	1409:1412	arg1	pathways					1424:1431	hyperactive mTOR signaling pathways	1397:1431	hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice	1397:1478	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	6	57	theme	mortality	1102:1110	arg1	rates					1112:1116	strikingly increased mortality rates	1081:1116	strikingly increased mortality rates	1081:1116	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	3	58	theme	ALG13	500:504	arg1	deficiency					506:515	ALG13 deficiency	500:515	ALG13 deficiency	500:515	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	8	59	theme	mice	1475:1478	arg1	cortex					1440:1445	cortex	1440:1445	cortex	1440:1445	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	8	59	theme	mice	1475:1478	arg1	hippocampus					1451:1461	hippocampus	1451:1461	hippocampus	1451:1461	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	5	60	from	forebrain	911:919	arg1	levels					871:876	the expression levels	856:876	the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice	856:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	8	61	theme	hyperactive	1397:1407	arg1	pathways					1424:1431	hyperactive mTOR signaling pathways	1397:1431	hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice	1397:1478	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	9	62	theme	first	1530:1534	arg1	report					1516:1521	this report	1511:1521	this report	1511:1521	To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
30872163	9	62	theme	first	1530:1534	arg1	evidence					1536:1543	the first evidence	1526:1543	the first evidence of the association between ALG13 and epilepsy in experimental animals	1526:1613	To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
30872163	7	63	theme	KO	1287:1288	arg1	mice					1290:1293	Alg13 KO mice	1281:1293	Alg13 KO mice	1281:1293	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	6	64	theme	KO	1026:1027	arg1	rates					1112:1116	strikingly increased mortality rates	1081:1116	strikingly increased mortality rates	1081:1116	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	64	theme	KO	1026:1027	arg1	seizures					1071:1078	prolonged electrographic seizures	1046:1078	prolonged electrographic seizures	1046:1078	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	64	theme	KO	1026:1027	arg1	mice					1030:1033	Alg13 knockout (KO) mice	1010:1033	Alg13 knockout (KO) mice	1010:1033	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	64	theme	KO	1026:1027	arg1	severity					1127:1134	the severity	1123:1134	the severity of responses to epileptic seizures	1123:1169	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	65	theme	prolonged	1046:1054	arg1	seizures					1071:1078	prolonged electrographic seizures	1046:1078	prolonged electrographic seizures	1046:1078	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	1	66	theme	crucial	141:147	arg1	ALG13					80:84	ALG13	80:84	ALG13 (asparagine-linked glycosylation 13 homolog)	80:129	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	1	66	theme	crucial	141:147	arg1	protein					149:155	a crucial protein	139:155	a crucial protein involved in the process of N-linked glycosylation	139:205	ALG13 (asparagine-linked glycosylation 13 homolog) encodes a crucial protein involved in the process of N-linked glycosylation, and abnormal N-linked glycosylation is considered an important risk factor that leads to neurological deficits and disorders.
30872163	8	67	theme	ALG13-involved	1362:1375	arg1	epilepsy					1377:1384	ALG13-involved epilepsy	1362:1384	ALG13-involved epilepsy	1362:1384	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	7	68	theme	brain	1241:1245	arg1	changes					1226:1232	KA-induced epilepsy-related pathological changes	1185:1232	KA-induced epilepsy-related pathological changes of the brain	1185:1245	Furthermore, KA-induced epilepsy-related pathological changes of the brain were predominantly exacerbated in Alg13 KO mice.
30872163	3	69	theme	epileptic	457:465	arg1	model					473:477	a kainic acid (KA)-induced epileptic mouse model	430:477	a kainic acid (KA)-induced epileptic mouse model	430:477	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	8	70	theme	KO	1472:1473	arg1	mice					1475:1478	Alg13 KO mice	1466:1478	Alg13 KO mice	1466:1478	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	5	71	theme	mRNA	887:890	arg1	levels					871:876	the expression levels	856:876	the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice	856:942	In addition, KA-induced seizures significantly affected the expression levels of ALG13 mRNA and protein in the forebrain of wild-type (WT) mice.
30872163	9	72	from	epilepsy	1582:1589	arg1	animals					1607:1613	experimental animals	1594:1613	experimental animals	1594:1613	To the best of our knowledge, this report is the first evidence of the association between ALG13 and epilepsy in experimental animals.
30872163	4	73	theme	ALG13	634:638	arg1	expression					620:629	the expression	616:629	the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity	616:718	This report found that the expression of ALG13 in the central nervous system (CNS) had histologically and cellular specificity, mainly in the neurons in the cortex and hippocampus, epilepsy commonly occurs.
30872163	8	74	theme	Alg13	1466:1470	arg1	mice					1475:1478	Alg13 KO mice	1466:1478	Alg13 KO mice	1466:1478	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	3	75	theme	increased	529:537	arg1	susceptibility					539:552	increased susceptibility	529:552	increased susceptibility to	529:555	This study applied a kainic acid (KA)-induced epileptic mouse model to determine whether ALG13 deficiency resulted in increased susceptibility to and severity of epileptic seizures.
30872163	8	76	from	pathways	1424:1431	arg1	cortex					1440:1445	cortex	1440:1445	cortex	1440:1445	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	8	76	from	pathways	1424:1431	arg1	hippocampus					1451:1461	hippocampus	1451:1461	hippocampus	1451:1461	This study also preliminarily explored the possible mechanisms of ALG13-involved epilepsy by showing hyperactive mTOR signaling pathways in the cortex and hippocampus of Alg13 KO mice.
30872163	6	77	theme	Alg13	1010:1014	arg1	rates					1112:1116	strikingly increased mortality rates	1081:1116	strikingly increased mortality rates	1081:1116	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	77	theme	Alg13	1010:1014	arg1	seizures					1071:1078	prolonged electrographic seizures	1046:1078	prolonged electrographic seizures	1046:1078	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	77	theme	Alg13	1010:1014	arg1	mice					1030:1033	Alg13 knockout (KO) mice	1010:1033	Alg13 knockout (KO) mice	1010:1033	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30872163	6	77	theme	Alg13	1010:1014	arg1	severity					1127:1134	the severity	1123:1134	the severity of responses to epileptic seizures	1123:1169	KA-induced epileptic progressions were dramatically increased in Alg13 knockout (KO) mice, including prolonged electrographic seizures, strikingly increased mortality rates, and the severity of responses to epileptic seizures.
30549167	3	0	theme	thiol	720:724	arg1	acceptors					726:734	thiol acceptors	720:734	thiol acceptors	720:734	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	5	1	theme	possible	902:909	arg1	acceptors					917:925	possible thiol acceptors	902:925	possible thiol acceptors	902:925	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	4	2	theme	quantitative	870:881	arg1	yields					883:888	nearly quantitative yields	863:888	nearly quantitative yields	863:888	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	5	3	theme	thiol	911:915	arg1	acceptors					917:925	possible thiol acceptors	902:925	possible thiol acceptors	902:925	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	1	4	theme	glycosides	257:266	arg1	role					249:252	the role	245:252	the role of glycosides in biological processes	245:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	3	5	theme	acceptors	726:734	arg1	set					713:715	a remarkably diverse set	692:715	a remarkably diverse set of thiol acceptors	692:734	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	3	5	theme	acceptors	726:734	arg1	acceptors					726:734	thiol acceptors	720:734	thiol acceptors	720:734	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	1	6	theme	biological	271:280	arg1	processes					282:290	biological processes	271:290	biological processes	271:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	0	7	theme	Mutant	101:106	arg1	Hexosaminidase					113:126	a Mutant GH20 Hexosaminidase	99:126	a Mutant GH20 Hexosaminidase	99:126	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.
30549167	5	8	theme	acceptors	917:925	arg1	set					895:897	The set	891:897	The set of possible thiol acceptors	891:925	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	5	8	theme	acceptors	917:925	arg1	acceptors					917:925	possible thiol acceptors	902:925	possible thiol acceptors	902:925	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	4	9	theme	6-thiosugar	773:783	arg1	acceptors					785:793	6-thiosugar acceptors	773:793	6-thiosugar acceptors	773:793	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	1	10	theme	O-linked	178:185	arg1	glycosides					187:196	O-linked glycosides	178:196	O-linked glycosides	178:196	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	4	11	link	S-linked	837:844	arg1	disaccharides					846:858	S-linked disaccharides	837:858	S-linked disaccharides in nearly quantitative yields	837:888	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	4	12	from	disaccharides	846:858	arg1	yields					883:888	nearly quantitative yields	863:888	nearly quantitative yields	863:888	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	4	13	theme	S-linked	837:844	arg1	disaccharides					846:858	S-linked disaccharides	837:858	S-linked disaccharides in nearly quantitative yields	837:888	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	0	14	theme	Facile	0:5	arg1	Formation					7:15	Facile Formation	0:15	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.	0:127	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.
30549167	5	15	theme	mutant	999:1004	arg1	enzyme					1006:1011	this mutant enzyme	994:1011	this mutant enzyme	994:1011	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	1	16	theme	glycosides	187:196	arg1	Thioglycosides					129:142	Thioglycosides	129:142	Thioglycosides	129:142	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	1	16	theme	glycosides	187:196	arg1	mimics					168:173	hydrolase-resistant mimics	148:173	hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes	148:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	1	16	theme	glycosides	187:196	arg1	probes					225:230	valuable probes	216:230	valuable probes for studying the role of glycosides in biological processes	216:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	2	17	from	plicatus	496:503	arg1	hexosaminidase					463:476	a GH20 hexosaminidase	456:476	a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A)	456:591	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	1	18	link	O-linked	178:185	arg1	glycosides					187:196	O-linked glycosides	178:196	O-linked glycosides	178:196	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	2	19	theme	GH20	458:461	arg1	hexosaminidase					463:476	a GH20 hexosaminidase	456:476	a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A)	456:591	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	2	20	theme	efficient	315:323	arg1	synthesis					342:350	an efficient, enzyme-mediated synthesis	312:350	an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins,	312:404	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	5	21	theme	peptides	1110:1117	arg1	analogues					1061:1069	thio analogues	1056:1069	thio analogues of biologically important GlcNAcylated peptides and proteins	1056:1130	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	0	22	theme	β-thioGlcNAc	20:31	arg1	Linkages					33:40	β-thioGlcNAc Linkages	20:40	β-thioGlcNAc Linkages	20:40	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.
30549167	4	23	theme	families	819:826	arg1	variety					802:808	a variety	800:808	a variety of sugar families	800:826	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	4	23	theme	families	819:826	arg1	families					819:826	sugar families	813:826	sugar families	813:826	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	5	24	theme	analogues	1061:1069	arg1	production					1042:1051	the production	1038:1051	the production of thio analogues of biologically important GlcNAcylated peptides and proteins	1038:1130	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	0	25	theme	GH20	108:111	arg1	Hexosaminidase					113:126	a Mutant GH20 Hexosaminidase	99:126	a Mutant GH20 Hexosaminidase	99:126	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.
30549167	5	26	theme	GlcNAcylated	1097:1108	arg1	peptides					1110:1117	biologically important GlcNAcylated peptides	1074:1117	biologically important GlcNAcylated peptides	1074:1117	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	2	27	dep	efficient	315:323	arg1	enzyme-mediated					326:340	enzyme-mediated	326:340	enzyme-mediated	326:340	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	2	28	attach	derived	443:449	arg1	hexosaminidase					463:476	a GH20 hexosaminidase	456:476	a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A)	456:591	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	2	28	attach	derived	443:449	arg2	thioglycoligase					427:441	a thioglycoligase	425:441	a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A)	425:591	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	4	29	theme	sugar	813:817	arg1	families					819:826	sugar families	813:826	sugar families	813:826	Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields.
30549167	1	30	theme	valuable	216:223	arg1	mimics					168:173	hydrolase-resistant mimics	148:173	hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes	148:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	1	30	theme	valuable	216:223	arg1	probes					225:230	valuable probes	216:230	valuable probes for studying the role of glycosides in biological processes	216:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	0	31	theme	Linkages	33:40	arg1	Formation					7:15	Facile Formation	0:15	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.	0:127	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.
30549167	5	32	theme	proteins	1123:1130	arg1	analogues					1061:1069	thio analogues	1056:1069	thio analogues of biologically important GlcNAcylated peptides and proteins	1056:1130	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	2	33	theme	thioglycosides	355:368	arg1	synthesis					342:350	an efficient, enzyme-mediated synthesis	312:350	an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins,	312:404	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	0	34	theme	Thiol-Containing	45:60	arg1	Sugars					62:67	Thiol-Containing Sugars	45:67	Thiol-Containing Sugars	45:67	Facile Formation of β-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.
30549167	1	35	from	role	249:252	arg1	processes					282:290	biological processes	271:290	biological processes	271:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	5	36	theme	thio	1056:1059	arg1	analogues					1061:1069	thio analogues	1056:1069	thio analogues of biologically important GlcNAcylated peptides and proteins	1056:1130	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	3	37	theme	robust	599:604	arg1	enzyme					635:640	This robust, easily-prepared, engineered enzyme	594:640	enzyme	635:640	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	2	38	theme	synthesis	342:350	arg1	development					297:307	The development	293:307	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins,	293:404	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	3	39	dep	GlcNAc	647:652	arg1	donors					665:670	donors	665:670	donors	665:670	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	5	40	theme	promising	1015:1023	arg1	catalyst					1025:1032	a promising catalyst	1013:1032	a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins	1013:1130	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	1	41	theme	hydrolase-resistant	148:166	arg1	Thioglycosides					129:142	Thioglycosides	129:142	Thioglycosides	129:142	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	1	41	theme	hydrolase-resistant	148:166	arg1	mimics					168:173	hydrolase-resistant mimics	148:173	hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes	148:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	1	41	theme	hydrolase-resistant	148:166	arg1	probes					225:230	valuable probes	216:230	valuable probes for studying the role of glycosides in biological processes	216:290	Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes.
30549167	5	42	theme	cysteine-containing	941:959	arg1	peptides					961:968	cysteine-containing peptides	941:968	cysteine-containing peptides	941:968	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	2	43	theme	acid/base	528:536	arg1	glutamate					538:546	the catalytic acid/base glutamate	514:546	the catalytic acid/base glutamate	514:546	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	5	44	theme	important	1087:1095	arg1	peptides					1110:1117	biologically important GlcNAcylated peptides	1074:1117	biologically important GlcNAcylated peptides	1074:1117	The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.
30549167	3	45	dep	robust	599:604	arg1	easily-prepared					607:621	easily-prepared	607:621	easily-prepared	607:621	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	2	46	theme	catalytic	518:526	arg1	glutamate					538:546	the catalytic acid/base glutamate	514:546	the catalytic acid/base glutamate	514:546	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30549167	3	47	theme	diverse	705:711	arg1	set					713:715	a remarkably diverse set	692:715	a remarkably diverse set of thiol acceptors	692:734	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	3	47	theme	diverse	705:711	arg1	acceptors					726:734	thiol acceptors	720:734	thiol acceptors	720:734	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	3	48	theme	engineered	624:633	arg1	enzyme					635:640	This robust, easily-prepared, engineered enzyme	594:640	enzyme	635:640	This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors.
30549167	2	49	theme	S-GlcNAcylated	381:394	arg1	proteins					396:403	S-GlcNAcylated proteins	381:403	S-GlcNAcylated proteins	381:403	The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A).
30364948	3	0	dep	modifications	564:576	arg1	N-acetylglucosamines					639:658	and O-linked and S-linked N-acetylglucosamines	613:658	and O-linked and S-linked N-acetylglucosamines	613:658	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	3	0	dep	modifications	564:576	arg1	pair					581:584	a pair	579:584	a pair of nested disulfide bonds	579:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	2	1	theme	extreme	466:472	arg1	conditions					474:483	extreme conditions	466:483	extreme conditions	466:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	3	2	theme	full	678:681	arg1	activity					683:690	full activity	678:690	full activity	678:690	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	2	3	theme	di-glycosylated	333:347	arg1	bacteriocin					349:359	an unusually di-glycosylated bacteriocin	320:359	an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions	320:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	3	theme	di-glycosylated	333:347	arg1	F					308:308	Glycocin F	299:308	Glycocin F (GccF)	299:315	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	3	4	link	S-linked	630:637	arg1	N-acetylglucosamines					639:658	and O-linked and S-linked N-acetylglucosamines	613:658	and O-linked and S-linked N-acetylglucosamines	613:658	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	3	4	link	S-linked	630:637	arg1	pair					581:584	a pair	579:584	a pair of nested disulfide bonds	579:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	8	5	theme	observed	1348:1355	arg1	increase					1357:1364	the observed increase	1344:1364	the observed increase in GccF concentration that accompanies an increase in cell numbers	1344:1431	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	0	6	theme	F	96:96	arg1	production					73:82	the production	69:82	the production of glycocin F in late log phase	69:114	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	8	7	theme	gcc	1248:1250	arg1	genes					1260:1264	the gcc cluster genes	1244:1264	the gcc cluster genes gccABCDEF	1244:1274	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	3	8	theme	post-translational	545:562	arg1	modifications					564:576	all its post-translational modifications	537:576	all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines)	537:659	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	0	9	theme	glycocin	87:94	arg1	F					96:96	glycocin F	87:96	glycocin F	87:96	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	0	10	theme	late	101:104	arg1	phase					110:114	late log phase	101:114	late log phase	101:114	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	5	11	theme	genes	817:821	arg1	expression					797:806	The expression	793:806	The expression	793:806	The expression of eight genes, previously reported to make up the gcc operon, was profiled for their expression during cell culture.
30364948	8	12	theme	cluster	1252:1258	arg1	genes					1260:1264	the gcc cluster genes	1244:1264	the gcc cluster genes gccABCDEF	1244:1274	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	2	13	theme	acid	382:385	arg1	bacterium					387:395	a lactic acid bacterium	373:395	a lactic acid bacterium	373:395	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	13	theme	acid	382:385	arg1	KW30					422:425	Lactobacillus plantarum KW30	398:425	Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions	398:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	7	14	theme	single	1198:1203	arg1	genes					1171:1175	the gcc genes	1163:1175	the gcc genes	1163:1175	We also found that most of the gcc genes are transcribed as a single unit.
30364948	7	14	theme	single	1198:1203	arg1	unit					1205:1208	a single unit	1196:1208	a single unit	1196:1208	We also found that most of the gcc genes are transcribed as a single unit.
30364948	7	14	theme	single	1198:1203	arg1	most					1155:1158	most	1155:1158	most	1155:1158	We also found that most of the gcc genes are transcribed as a single unit.
30364948	6	15	from	increase	1108:1115	arg1	secretion					1125:1133	GccF secretion	1120:1133	GccF secretion	1120:1133	We found that all but one of the genes of the gcc cluster followed a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion.
30364948	2	16	theme	lactic	375:380	arg1	bacterium					387:395	a lactic acid bacterium	373:395	a lactic acid bacterium	373:395	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	16	theme	lactic	375:380	arg1	KW30					422:425	Lactobacillus plantarum KW30	398:425	Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions	398:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	8	17	theme	cell	1420:1423	arg1	numbers					1425:1431	cell numbers	1420:1431	cell numbers	1420:1431	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	0	18	theme	plantarum	28:36	arg1	genes					47:51	Lactobacillus plantarum KW30 gcc genes	14:51	Lactobacillus plantarum KW30 gcc genes	14:51	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	1	19	theme	related	281:287	arg1	bacteria					289:296	closely related bacteria	273:296	closely related bacteria	273:296	Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria.
30364948	5	20	theme	cell	912:915	arg1	culture					917:923	cell culture	912:923	cell culture	912:923	The expression of eight genes, previously reported to make up the gcc operon, was profiled for their expression during cell culture.
30364948	6	21	theme	expression	1006:1015	arg1	pattern					995:1001	a pattern	993:1001	a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion	993:1133	We found that all but one of the genes of the gcc cluster followed a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion.
30364948	8	22	dep	genes	1260:1264	arg1	gccABCDEF					1266:1274	gccABCDEF	1266:1274	the gcc cluster genes gccABCDEF	1244:1274	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	0	23	theme	Lactobacillus	14:26	arg1	genes					47:51	Lactobacillus plantarum KW30 gcc genes	14:51	Lactobacillus plantarum KW30 gcc genes	14:51	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	1	24	theme	bacteria	289:296	arg1	growth					263:268	the growth	259:268	the growth of closely related bacteria	259:296	Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria.
30364948	0	25	theme	log	106:108	arg1	phase					110:114	late log phase	101:114	late log phase	101:114	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	3	26	theme	S-linked	630:637	arg1	N-acetylglucosamines					639:658	and O-linked and S-linked N-acetylglucosamines	613:658	and O-linked and S-linked N-acetylglucosamines	613:658	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	3	26	theme	S-linked	630:637	arg1	pair					581:584	a pair	579:584	a pair of nested disulfide bonds	579:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	2	27	theme	Glycocin	299:306	arg1	F					308:308	Glycocin F	299:308	Glycocin F (GccF)	299:315	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	27	theme	Glycocin	299:306	arg1	bacteriocin					349:359	an unusually di-glycosylated bacteriocin	320:359	an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions	320:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	27	theme	Glycocin	299:306	arg1	GccF					311:314	GccF	311:314	GccF	311:314	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	28	theme	plantarum	412:420	arg1	bacterium					387:395	a lactic acid bacterium	373:395	a lactic acid bacterium	373:395	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	28	theme	plantarum	412:420	arg1	KW30					422:425	Lactobacillus plantarum KW30	398:425	Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions	398:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	0	29	theme	gcc	43:45	arg1	genes					47:51	Lactobacillus plantarum KW30 gcc genes	14:51	Lactobacillus plantarum KW30 gcc genes	14:51	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	2	30	gly	di-glycosylated	333:347	arg1	bacteriocin					349:359	an unusually di-glycosylated bacteriocin	320:359	an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions	320:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	30	gly	di-glycosylated	333:347	arg1	F					308:308	Glycocin F	299:308	Glycocin F (GccF)	299:315	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	0	31	from	production	73:82	arg1	phase					110:114	late log phase	101:114	late log phase	101:114	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	2	32	theme	Lactobacillus	398:410	arg1	bacterium					387:395	a lactic acid bacterium	373:395	a lactic acid bacterium	373:395	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	2	32	theme	Lactobacillus	398:410	arg1	KW30					422:425	Lactobacillus plantarum KW30	398:425	Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions	398:483	Glycocin F (GccF) is an unusually di-glycosylated bacteriocin produced in a lactic acid bacterium, Lactobacillus plantarum KW30 that has been shown to be resistant to extreme conditions.
30364948	0	33	theme	KW30	38:41	arg1	genes					47:51	Lactobacillus plantarum KW30 gcc genes	14:51	Lactobacillus plantarum KW30 gcc genes	14:51	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	3	34	theme	O-linked	617:624	arg1	N-acetylglucosamines					639:658	and O-linked and S-linked N-acetylglucosamines	613:658	and O-linked and S-linked N-acetylglucosamines	613:658	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	3	34	theme	O-linked	617:624	arg1	pair					581:584	a pair	579:584	a pair of nested disulfide bonds	579:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	3	35	theme	nested	589:594	arg1	bonds					606:610	nested disulfide bonds	589:610	nested disulfide bonds	589:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	6	36	theme	gcc	972:974	arg1	cluster					976:982	the gcc cluster	968:982	the gcc cluster	968:982	We found that all but one of the genes of the gcc cluster followed a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion.
30364948	8	37	from	increase	1408:1415	arg1	numbers					1425:1431	cell numbers	1420:1431	cell numbers	1420:1431	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	8	38	theme	GccF	1315:1318	arg1	production					1320:1329	regulated GccF production	1305:1329	regulated GccF production	1305:1329	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	0	39	theme	genes	47:51	arg1	Expression					0:9	Expression	0:9	Expression of Lactobacillus plantarum KW30 gcc genes	0:51	Expression of Lactobacillus plantarum KW30 gcc genes correlates with the production of glycocin F in late log phase.
30364948	8	40	theme	regulated	1305:1313	arg1	production					1320:1329	regulated GccF production	1305:1329	regulated GccF production	1305:1329	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	6	41	theme	GccF	1120:1123	arg1	secretion					1125:1133	GccF secretion	1120:1133	GccF secretion	1120:1133	We found that all but one of the genes of the gcc cluster followed a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion.
30364948	8	42	theme	GccF	1369:1372	arg1	concentration					1374:1386	GccF concentration	1369:1386	GccF concentration	1369:1386	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	6	43	theme	growth	1051:1056	arg1	stage					1042:1046	the stage	1038:1046	the stage of growth observed for the producer organism along with the increase in GccF secretion	1038:1133	We found that all but one of the genes of the gcc cluster followed a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion.
30364948	6	44	theme	producer	1075:1082	arg1	organism					1084:1091	the producer organism	1071:1091	the producer organism	1071:1091	We found that all but one of the genes of the gcc cluster followed a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion.
30364948	4	45	theme	GccF	761:764	arg1	expression					766:775	GccF expression	761:775	GccF expression	761:775	Here, we examine a cluster of genes predicted to be responsible for GccF expression and maturation.
30364948	4	46	theme	genes	723:727	arg1	cluster					712:718	a cluster	710:718	a cluster of genes predicted to be responsible for GccF expression and maturation	710:790	Here, we examine a cluster of genes predicted to be responsible for GccF expression and maturation.
30364948	1	47	theme	Antibacterial	117:129	arg1	inventions					177:186	microbial inventions	167:186	microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria	167:296	Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria.
30364948	1	47	theme	Antibacterial	117:129	arg1	compounds					131:139	Antibacterial compounds	117:139	Antibacterial compounds known as bacteriocins	117:161	Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria.
30364948	1	48	theme	limited	227:233	arg1	resources					235:243	limited resources	227:243	limited resources	227:243	Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria.
30364948	8	49	theme	true	1289:1292	arg1	operon					1294:1299	a true operon	1287:1299	a true operon for regulated GccF production	1287:1329	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	3	50	theme	disulfide	596:604	arg1	bonds					606:610	nested disulfide bonds	589:610	nested disulfide bonds	589:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	7	51	theme	gcc	1167:1169	arg1	genes					1171:1175	the gcc genes	1163:1175	the gcc genes	1163:1175	We also found that most of the gcc genes are transcribed as a single unit.
30364948	1	52	theme	microbial	167:175	arg1	inventions					177:186	microbial inventions	167:186	microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria	167:296	Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria.
30364948	1	52	theme	microbial	167:175	arg1	compounds					131:139	Antibacterial compounds	117:139	Antibacterial compounds known as bacteriocins	117:161	Antibacterial compounds known as bacteriocins are microbial inventions designed to reduce the competition for limited resources by inhibiting the growth of closely related bacteria.
30364948	8	53	from	increase	1357:1364	arg1	concentration					1374:1386	GccF concentration	1369:1386	GccF concentration	1369:1386	These data provide evidence that the gcc cluster genes gccABCDEF constitute a true operon for regulated GccF production, and explain the observed increase in GccF concentration that accompanies an increase in cell numbers.
30364948	3	54	theme	bonds	606:610	arg1	N-acetylglucosamines					639:658	and O-linked and S-linked N-acetylglucosamines	613:658	and O-linked and S-linked N-acetylglucosamines	613:658	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	3	54	theme	bonds	606:610	arg1	pair					581:584	a pair	579:584	a pair of nested disulfide bonds	579:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	5	55	theme	gcc	859:861	arg1	operon					863:868	the gcc operon	855:868	the gcc operon	855:868	The expression of eight genes, previously reported to make up the gcc operon, was profiled for their expression during cell culture.
30364948	3	56	link	O-linked	617:624	arg1	N-acetylglucosamines					639:658	and O-linked and S-linked N-acetylglucosamines	613:658	and O-linked and S-linked N-acetylglucosamines	613:658	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	3	56	link	O-linked	617:624	arg1	pair					581:584	a pair	579:584	a pair of nested disulfide bonds	579:610	It is bacteriostatic rather than bactericidal, and all its post-translational modifications (a pair of nested disulfide bonds, and O-linked and S-linked N-acetylglucosamines) are required for full activity.
30364948	6	57	theme	cluster	976:982	arg1	genes					959:963	the genes	955:963	the genes of the gcc cluster	955:982	We found that all but one of the genes of the gcc cluster followed a pattern of expression that correlated with the stage of growth observed for the producer organism along with the increase in GccF secretion.
30257210	5	0	theme	other	696:700	arg1	proteins					702:709	other proteins	696:709	other proteins	696:709	We also broaden the O-linked ADPr spectrum by providing evidence for tyrosine ADPr on HPF1 and other proteins.
30257210	1	1	from	PARP2	169:173	arg1	complex					183:189	complex	183:189	complex with the eponymous histone PARylation factor 1 (HPF1)	183:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	4	2	theme	H3K9	532:535	arg1	methylation					517:527	methylation	517:527	methylation of H3K9	517:535	Most notably, acetylation, but not methylation of H3K9, is mutually exclusive with ADPr of H3S10 in vitro and in vivo.
30257210	5	3	link	O-linked	621:628	arg1	spectrum					635:642	the O-linked ADPr spectrum	617:642	the O-linked ADPr spectrum	617:642	We also broaden the O-linked ADPr spectrum by providing evidence for tyrosine ADPr on HPF1 and other proteins.
30257210	1	4	from	PARP1	159:163	arg1	complex					183:189	complex	183:189	complex with the eponymous histone PARylation factor 1 (HPF1)	183:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	2	5	theme	numerous	261:268	arg1	targets					276:282	numerous other targets	261:282	numerous other targets	261:282	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	5	6	theme	tyrosine	670:677	arg1	ADPr					679:682	tyrosine ADPr	670:682	tyrosine ADPr	670:682	We also broaden the O-linked ADPr spectrum by providing evidence for tyrosine ADPr on HPF1 and other proteins.
30257210	6	7	theme	wider	735:739	arg1	investigations					741:754	wider investigations	735:754	wider investigations into the interplay of histone marks with Ser-ADPr	735:804	Finally, we facilitate wider investigations into the interplay of histone marks with Ser-ADPr by introducing a simple approach for profiling posttranslationally modified peptides.
30257210	1	8	theme	discovered	106:115	arg1	modification					125:136	a recently discovered protein modification	95:136	a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1)	95:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	8	theme	discovered	106:115	arg1	ADP-ribosylation					64:79	Serine ADP-ribosylation	57:79	Serine ADP-ribosylation (Ser-ADPr)	57:90	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	3	9	theme	specific	385:392	arg1	histone					404:410	specific canonical histone	385:410	specific canonical histone	385:410	Here, we show that specific canonical histone marks interfere with Ser-ADPr of neighboring residues and vice versa.
30257210	7	10	dep	histone	1003:1009	arg1	code					1011:1014	code	1011:1014	code	1011:1014	Our findings implicate Ser-ADPr as a dynamic addition to the complex interplay of modifications that shape the histone code.
30257210	3	11	theme	neighboring	445:455	arg1	residues					457:464	neighboring residues	445:464	neighboring residues	445:464	Here, we show that specific canonical histone marks interfere with Ser-ADPr of neighboring residues and vice versa.
30257210	2	12	theme	damage	349:354	arg1	response					356:363	the DNA damage response	341:363	the DNA damage response	341:363	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	2	13	from	acceptors	316:324	arg1	response					356:363	the DNA damage response	341:363	the DNA damage response	341:363	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	2	14	theme	core	285:288	arg1	tails					298:302	core histone tails	285:302	core histone tails	285:302	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	2	14	theme	core	285:288	arg1	acceptors					316:324	primary acceptors	308:324	primary acceptors of Ser-ADPr	308:336	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	6	15	theme	simple	823:828	arg1	approach					830:837	a simple approach	821:837	a simple approach for profiling posttranslationally modified peptides	821:889	Finally, we facilitate wider investigations into the interplay of histone marks with Ser-ADPr by introducing a simple approach for profiling posttranslationally modified peptides.
30257210	2	16	theme	DNA	345:347	arg1	damage					349:354	DNA damage	345:354	the DNA damage response	341:363	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	4	17	theme	H3S10	573:577	arg1	in vitro					579:586	H3S10 in vitro	573:586	H3S10 in vitro	573:586	Most notably, acetylation, but not methylation of H3K9, is mutually exclusive with ADPr of H3S10 in vitro and in vivo.
30257210	0	18	theme	Histone	13:19	arg1	Interplay					0:8	Interplay	0:8	Interplay of Histone	0:19	Interplay of Histone Marks with Serine ADP-Ribosylation.
30257210	6	19	dep	histone	778:784	arg1	marks					786:790	marks	786:790	marks	786:790	Finally, we facilitate wider investigations into the interplay of histone marks with Ser-ADPr by introducing a simple approach for profiling posttranslationally modified peptides.
30257210	2	20	theme	other	270:274	arg1	targets					276:282	numerous other targets	261:282	numerous other targets	261:282	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	4	21	theme	in vivo	592:598	arg1	ADPr					565:568	ADPr	565:568	ADPr of H3S10 in vitro and in vivo	565:598	Most notably, acetylation, but not methylation of H3K9, is mutually exclusive with ADPr of H3S10 in vitro and in vivo.
30257210	0	22	theme	Serine	32:37	arg1	ADP-Ribosylation					39:54	Serine ADP-Ribosylation	32:54	Serine ADP-Ribosylation	32:54	Interplay of Histone Marks with Serine ADP-Ribosylation.
30257210	3	23	theme	residues	457:464	arg1	Ser-ADPr					433:440	Ser-ADPr	433:440	Ser-ADPr of neighboring residues	433:464	Here, we show that specific canonical histone marks interfere with Ser-ADPr of neighboring residues and vice versa.
30257210	1	24	with	complex	183:189	arg1	factor					229:234	the eponymous histone PARylation factor 1	196:236	the eponymous histone PARylation factor 1 (HPF1)	196:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	24	with	complex	183:189	arg1	HPF1					239:242	HPF1	239:242	HPF1	239:242	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	6	25	with	histone	778:784	arg1	Ser-ADPr					797:804	Ser-ADPr	797:804	Ser-ADPr	797:804	Finally, we facilitate wider investigations into the interplay of histone marks with Ser-ADPr by introducing a simple approach for profiling posttranslationally modified peptides.
30257210	1	26	theme	eponymous	200:208	arg1	factor					229:234	the eponymous histone PARylation factor 1	196:236	the eponymous histone PARylation factor 1 (HPF1)	196:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	26	theme	eponymous	200:208	arg1	HPF1					239:242	HPF1	239:242	HPF1	239:242	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	4	27	with	exclusive	550:558	arg1	ADPr					565:568	ADPr	565:568	ADPr of H3S10 in vitro and in vivo	565:598	Most notably, acetylation, but not methylation of H3K9, is mutually exclusive with ADPr of H3S10 in vitro and in vivo.
30257210	7	28	theme	modifications	974:986	arg1	interplay					961:969	the complex interplay	949:969	the complex interplay of modifications that shape the histone code	949:1014	Our findings implicate Ser-ADPr as a dynamic addition to the complex interplay of modifications that shape the histone code.
30257210	2	29	theme	primary	308:314	arg1	tails					298:302	core histone tails	285:302	core histone tails	285:302	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	2	29	theme	primary	308:314	arg1	acceptors					316:324	primary acceptors	308:324	primary acceptors of Ser-ADPr	308:336	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	6	30	theme	histone	778:784	arg1	interplay					765:773	the interplay	761:773	the interplay of histone marks with Ser-ADPr	761:804	Finally, we facilitate wider investigations into the interplay of histone marks with Ser-ADPr by introducing a simple approach for profiling posttranslationally modified peptides.
30257210	7	31	theme	complex	953:959	arg1	interplay					961:969	the complex interplay	949:969	the complex interplay of modifications that shape the histone code	949:1014	Our findings implicate Ser-ADPr as a dynamic addition to the complex interplay of modifications that shape the histone code.
30257210	1	32	theme	protein	117:123	arg1	modification					125:136	a recently discovered protein modification	95:136	a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1)	95:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	32	theme	protein	117:123	arg1	ADP-ribosylation					64:79	Serine ADP-ribosylation	57:79	Serine ADP-ribosylation (Ser-ADPr)	57:90	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	5	33	theme	O-linked	621:628	arg1	spectrum					635:642	the O-linked ADPr spectrum	617:642	the O-linked ADPr spectrum	617:642	We also broaden the O-linked ADPr spectrum by providing evidence for tyrosine ADPr on HPF1 and other proteins.
30257210	1	34	theme	histone	210:216	arg1	factor					229:234	the eponymous histone PARylation factor 1	196:236	the eponymous histone PARylation factor 1 (HPF1)	196:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	34	theme	histone	210:216	arg1	HPF1					239:242	HPF1	239:242	HPF1	239:242	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	5	35	theme	ADPr	630:633	arg1	spectrum					635:642	the O-linked ADPr spectrum	617:642	the O-linked ADPr spectrum	617:642	We also broaden the O-linked ADPr spectrum by providing evidence for tyrosine ADPr on HPF1 and other proteins.
30257210	1	36	theme	Serine	57:62	arg1	modification					125:136	a recently discovered protein modification	95:136	a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1)	95:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	36	theme	Serine	57:62	arg1	Ser-ADPr					82:89	Ser-ADPr	82:89	Ser-ADPr	82:89	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	36	theme	Serine	57:62	arg1	ADP-ribosylation					64:79	Serine ADP-ribosylation	57:79	Serine ADP-ribosylation (Ser-ADPr)	57:90	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	2	37	theme	histone	290:296	arg1	tails					298:302	core histone tails	285:302	core histone tails	285:302	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	2	37	theme	histone	290:296	arg1	acceptors					316:324	primary acceptors	308:324	primary acceptors of Ser-ADPr	308:336	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	1	38	theme	PARylation	218:227	arg1	factor					229:234	the eponymous histone PARylation factor 1	196:236	the eponymous histone PARylation factor 1 (HPF1)	196:243	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	1	38	theme	PARylation	218:227	arg1	HPF1					239:242	HPF1	239:242	HPF1	239:242	Serine ADP-ribosylation (Ser-ADPr) is a recently discovered protein modification that is catalyzed by PARP1 and PARP2 when in complex with the eponymous histone PARylation factor 1 (HPF1).
30257210	4	39	theme	in vitro	579:586	arg1	ADPr					565:568	ADPr	565:568	ADPr of H3S10 in vitro and in vivo	565:598	Most notably, acetylation, but not methylation of H3K9, is mutually exclusive with ADPr of H3S10 in vitro and in vivo.
30257210	3	40	dep	interfere	418:426	arg1	Ser-ADPr					433:440	Ser-ADPr	433:440	Ser-ADPr of neighboring residues	433:464	Here, we show that specific canonical histone marks interfere with Ser-ADPr of neighboring residues and vice versa.
30257210	3	40	dep	interfere	418:426	arg1	versa					475:479	versa	475:479	versa	475:479	Here, we show that specific canonical histone marks interfere with Ser-ADPr of neighboring residues and vice versa.
30257210	3	41	theme	canonical	394:402	arg1	histone					404:410	specific canonical histone	385:410	specific canonical histone	385:410	Here, we show that specific canonical histone marks interfere with Ser-ADPr of neighboring residues and vice versa.
30257210	6	42	theme	modified	873:880	arg1	peptides					882:889	posttranslationally modified peptides	853:889	posttranslationally modified peptides	853:889	Finally, we facilitate wider investigations into the interplay of histone marks with Ser-ADPr by introducing a simple approach for profiling posttranslationally modified peptides.
30257210	7	43	theme	dynamic	929:935	arg1	Ser-ADPr					915:922	Ser-ADPr	915:922	Ser-ADPr	915:922	Our findings implicate Ser-ADPr as a dynamic addition to the complex interplay of modifications that shape the histone code.
30257210	7	43	theme	dynamic	929:935	arg1	addition					937:944	a dynamic addition	927:944	a dynamic addition to the complex interplay of modifications that shape the histone code	927:1014	Our findings implicate Ser-ADPr as a dynamic addition to the complex interplay of modifications that shape the histone code.
30257210	2	44	theme	Ser-ADPr	329:336	arg1	tails					298:302	core histone tails	285:302	core histone tails	285:302	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30257210	2	44	theme	Ser-ADPr	329:336	arg1	acceptors					316:324	primary acceptors	308:324	primary acceptors of Ser-ADPr	308:336	In addition to numerous other targets, core histone tails are primary acceptors of Ser-ADPr in the DNA damage response.
30036038	8	0	theme	O-linked	1302:1309	arg1	glycoproteins					1311:1323	O-linked glycoproteins	1302:1323	O-linked glycoproteins	1302:1323	The strategy is particularly significant for the recognition of O-glycans, because enzymes that can release O-glycans from O-linked glycoproteins are lacking.
30036038	5	1	dep	in	876:877	arg1	situ					879:882	situ	879:882	situ	879:882	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	1	2	theme	many	166:169	arg1	researches					250:259	fundamental researches	238:259	fundamental researches	238:259	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	1	2	theme	many	166:169	arg1	fields					181:186	many important fields	166:186	many important fields	166:186	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	1	2	theme	many	166:169	arg1	therapeutics					220:231	therapeutics	220:231	therapeutics	220:231	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	1	2	theme	many	166:169	arg1	diagnostics					207:217	disease diagnostics	199:217	disease diagnostics	199:217	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	0	3	theme	Antibodies	91:100	arg1	Preparation					49:59	Facile Preparation	42:59	Facile Preparation of Glycan-Specific Artificial Antibodies	42:100	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.
30036038	9	4	theme	excellent	1357:1365	arg1	specificity					1374:1384	excellent glycan specificity	1357:1384	excellent glycan specificity	1357:1384	The MIPs exhibited excellent glycan specificity.
30036038	2	5	theme	antibody	361:368	arg1	development					370:380	antibody development	361:380	antibody development	361:380	However, due to their low immunogenicity and poor availability, glycans pose serious challenges to antibody development.
30036038	11	6	theme	glycan-related	1607:1620	arg1	applications					1622:1633	glycan-related applications	1607:1633	glycan-related applications	1607:1633	This strategy opened a new avenue for the facile preparation of glycan-specific MIPs, facilitating glycan-related applications and research.
30036038	7	7	gly	glycoproteins	1024:1036	arg1	glycoproteins					1024:1036	glycoproteins	1024:1036	glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source	1024:1112	With glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source, this approach was proved to be widely applicable and efficient.
30036038	9	8	theme	glycan	1367:1372	arg1	specificity					1374:1384	excellent glycan specificity	1357:1384	excellent glycan specificity	1357:1384	The MIPs exhibited excellent glycan specificity.
30036038	10	9	theme	complex	1474:1480	arg1	samples					1482:1488	complex samples	1474:1488	complex samples	1474:1488	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	1	10	theme	important	171:179	arg1	researches					250:259	fundamental researches	238:259	fundamental researches	238:259	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	1	10	theme	important	171:179	arg1	fields					181:186	many important fields	166:186	many important fields	166:186	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	1	10	theme	important	171:179	arg1	therapeutics					220:231	therapeutics	220:231	therapeutics	220:231	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	1	10	theme	important	171:179	arg1	diagnostics					207:217	disease diagnostics	199:217	disease diagnostics	199:217	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	10	11	gly	glycoproteins	1428:1440	arg1	glycoproteins					1428:1440	glycoproteins	1428:1440	glycoproteins	1428:1440	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	1	12	from	areas	156:160	arg1	essential					138:146	essential	138:146	essential	138:146	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	3	13	theme	imprinted	547:555	arg1	mimics					476:481	antibody mimics	467:481	antibody mimics with low cost and better stability	467:516	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	3	13	theme	imprinted	547:555	arg1	polymers					557:564	glycan-specific molecularly imprinted polymers	519:564	glycan-specific molecularly imprinted polymers (MIPs)	519:571	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	3	13	theme	imprinted	547:555	arg1	MIPs					567:570	MIPs	567:570	MIPs	567:570	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	4	14	theme	MIPs	728:731	arg1	preparation					697:707	the facile preparation	686:707	the facile preparation of glycan-specific MIPs	686:731	Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs.
30036038	5	15	theme	enzymatic	889:897	arg1	digestion					899:907	in situ dual enzymatic digestion	876:907	in situ dual enzymatic digestion	876:907	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	2	16	theme	low	284:286	arg1	immunogenicity					288:301	their low immunogenicity	278:301	their low immunogenicity	278:301	However, due to their low immunogenicity and poor availability, glycans pose serious challenges to antibody development.
30036038	5	17	theme	alternative	846:856	arg1	Glycopeptides					734:746	Glycopeptides	734:746	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate	734:821	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	5	17	theme	alternative	846:856	arg1	templates					858:866	alternative templates	846:866	alternative templates	846:866	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	8	18	theme	O-glycans	1243:1251	arg1	recognition					1228:1238	the recognition	1224:1238	the recognition of O-glycans	1224:1251	The strategy is particularly significant for the recognition of O-glycans, because enzymes that can release O-glycans from O-linked glycoproteins are lacking.
30036038	5	19	theme	boronate	795:802	arg1	substrate					813:821	a boronate affinity substrate	793:821	a boronate affinity substrate	793:821	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	11	20	theme	new	1531:1533	arg1	avenue					1535:1540	a new avenue	1529:1540	a new avenue for the facile preparation of glycan-specific MIPs	1529:1591	This strategy opened a new avenue for the facile preparation of glycan-specific MIPs, facilitating glycan-related applications and research.
30036038	0	21	theme	Precision	0:8	arg1	Imprinting					10:19	Precision Imprinting	0:19	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.	0:101	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.
30036038	8	22	link	O-linked	1302:1309	arg1	glycoproteins					1311:1323	O-linked glycoproteins	1302:1323	O-linked glycoproteins	1302:1323	The strategy is particularly significant for the recognition of O-glycans, because enzymes that can release O-glycans from O-linked glycoproteins are lacking.
30036038	1	23	theme	specific	114:121	arg1	Antibodies					103:112	Antibodies	103:112	Antibodies specific to glycans	103:132	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	3	24	theme	antibody	467:474	arg1	mimics					476:481	antibody mimics	467:481	antibody mimics with low cost and better stability	467:516	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	3	24	theme	antibody	467:474	arg1	polymers					557:564	glycan-specific molecularly imprinted polymers	519:564	glycan-specific molecularly imprinted polymers (MIPs)	519:571	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	0	25	theme	Glycopeptides	24:36	arg1	Imprinting					10:19	Precision Imprinting	0:19	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.	0:101	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.
30036038	1	26	from	essential	138:146	arg1	areas					156:160	many areas	151:160	many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches	151:259	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	10	27	theme	Specific	1387:1394	arg1	extraction					1396:1405	Specific extraction	1387:1405	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples	1387:1488	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	4	28	theme	alternative	659:669	arg1	templates					671:679	alternative templates	659:679	alternative templates	659:679	Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs.
30036038	2	29	theme	poor	307:310	arg1	availability					312:323	poor availability	307:323	poor availability	307:323	However, due to their low immunogenicity and poor availability, glycans pose serious challenges to antibody development.
30036038	3	30	theme	better	501:506	arg1	stability					508:516	better stability	501:516	better stability	501:516	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	0	31	theme	Facile	42:47	arg1	Preparation					49:59	Facile Preparation	42:59	Facile Preparation of Glycan-Specific Artificial Antibodies	42:100	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.
30036038	5	32	theme	desirable	753:761	arg1	length					771:776	desirable peptide length	753:776	desirable peptide length immobilized on a boronate affinity substrate	753:821	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	5	33	with	Glycopeptides	734:746	arg1	length					771:776	desirable peptide length	753:776	desirable peptide length immobilized on a boronate affinity substrate	753:821	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	4	34	with	imprinting	643:652	arg1	templates					671:679	alternative templates	659:679	alternative templates	659:679	Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs.
30036038	1	35	theme	disease	199:205	arg1	diagnostics					207:217	disease diagnostics	199:217	disease diagnostics	199:217	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	3	36	theme	low	488:490	arg1	cost					492:495	low cost	488:495	low cost	488:495	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	11	37	theme	facile	1550:1555	arg1	preparation					1557:1567	the facile preparation	1546:1567	the facile preparation of glycan-specific MIPs	1546:1591	This strategy opened a new avenue for the facile preparation of glycan-specific MIPs, facilitating glycan-related applications and research.
30036038	10	38	contain	containing	1442:1451	arg2	glycans					1461:1467	certain glycans	1453:1467	certain glycans	1453:1467	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	10	38	contain	containing	1442:1451	arg1	glycopeptides					1410:1422	glycopeptides	1410:1422	glycopeptides	1410:1422	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	5	39	theme	peptide	763:769	arg1	length					771:776	desirable peptide length	753:776	desirable peptide length immobilized on a boronate affinity substrate	753:821	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	3	40	theme	molecular	392:400	arg1	imprinting					402:411	molecular imprinting	392:411	molecular imprinting	392:411	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	10	41	theme	glycoproteins	1428:1440	arg1	extraction					1396:1405	Specific extraction	1387:1405	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples	1387:1488	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	5	42	theme	in	876:877	arg1	digestion					899:907	in situ dual enzymatic digestion	876:907	in situ dual enzymatic digestion	876:907	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	7	43	contain	containing	1038:1047	arg2	N-					1080:1081	N-	1080:1081	N-	1080:1081	With glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source, this approach was proved to be widely applicable and efficient.
30036038	7	43	contain	containing	1038:1047	arg1	glycoproteins					1024:1036	glycoproteins	1024:1036	glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source	1024:1112	With glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source, this approach was proved to be widely applicable and efficient.
30036038	7	43	contain	containing	1038:1047	arg2	N-glycans					1054:1062	only N-glycans	1049:1062	only N-glycans as well as both N- and O-glycans	1049:1095	With glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source, this approach was proved to be widely applicable and efficient.
30036038	6	44	theme	precision	997:1005	arg1	imprinting					1007:1016	precision imprinting	997:1016	precision imprinting	997:1016	A thinlayer was then produced to cover the glycans to an appropriate thickness through precision imprinting.
30036038	7	45	theme	glycan	1100:1105	arg1	source					1107:1112	glycan source	1100:1112	glycan source	1100:1112	With glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source, this approach was proved to be widely applicable and efficient.
30036038	5	46	theme	affinity	804:811	arg1	substrate					813:821	a boronate affinity substrate	793:821	a boronate affinity substrate	793:821	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	3	47	theme	glycan-specific	519:533	arg1	mimics					476:481	antibody mimics	467:481	antibody mimics with low cost and better stability	467:516	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	3	47	theme	glycan-specific	519:533	arg1	polymers					557:564	glycan-specific molecularly imprinted polymers	519:564	glycan-specific molecularly imprinted polymers (MIPs)	519:571	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	3	47	theme	glycan-specific	519:533	arg1	MIPs					567:570	MIPs	567:570	MIPs	567:570	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	3	48	theme	important	432:440	arg1	methodology					442:452	important methodology	432:452	important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs)	432:571	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	10	49	gly	glycopeptides	1410:1422	arg2	glycopeptides					1410:1422	glycopeptides	1410:1422	glycopeptides	1410:1422	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	4	50	theme	new	619:621	arg1	strategy					623:630	a new strategy	617:630	a new strategy	617:630	Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs.
30036038	10	51	theme	glycopeptides	1410:1422	arg1	extraction					1396:1405	Specific extraction	1387:1405	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples	1387:1488	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	4	52	theme	facile	690:695	arg1	preparation					697:707	the facile preparation	686:707	the facile preparation of glycan-specific MIPs	686:731	Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs.
30036038	3	53	with	mimics	476:481	arg1	cost					492:495	low cost	488:495	low cost	488:495	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	3	53	with	mimics	476:481	arg1	stability					508:516	better stability	501:516	better stability	501:516	Although molecular imprinting has developed into important methodology for creating antibody mimics with low cost and better stability, glycan-specific molecularly imprinted polymers (MIPs) still remain rather rare.
30036038	2	54	theme	serious	339:345	arg1	challenges					347:356	serious challenges	339:356	serious challenges to antibody development	339:380	However, due to their low immunogenicity and poor availability, glycans pose serious challenges to antibody development.
30036038	10	55	theme	certain	1453:1459	arg1	glycans					1461:1467	certain glycans	1453:1467	certain glycans	1453:1467	Specific extraction of glycopeptides and glycoproteins containing certain glycans from complex samples was demonstrated.
30036038	8	56	gly	glycoproteins	1311:1323	arg1	glycoproteins					1311:1323	O-linked glycoproteins	1302:1323	O-linked glycoproteins	1302:1323	The strategy is particularly significant for the recognition of O-glycans, because enzymes that can release O-glycans from O-linked glycoproteins are lacking.
30036038	1	57	theme	many	151:154	arg1	areas					156:160	many areas	151:160	many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches	151:259	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	11	58	theme	glycan-specific	1572:1586	arg1	MIPs					1588:1591	glycan-specific MIPs	1572:1591	glycan-specific MIPs	1572:1591	This strategy opened a new avenue for the facile preparation of glycan-specific MIPs, facilitating glycan-related applications and research.
30036038	1	59	theme	fundamental	238:248	arg1	researches					250:259	fundamental researches	238:259	fundamental researches	238:259	Antibodies specific to glycans are essential in many areas for many important fields, including disease diagnostics, therapeutics, and fundamental researches.
30036038	0	60	theme	Artificial	80:89	arg1	Antibodies					91:100	Glycan-Specific Artificial Antibodies	64:100	Glycan-Specific Artificial Antibodies	64:100	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.
30036038	5	61	theme	dual	884:887	arg1	digestion					899:907	in situ dual enzymatic digestion	876:907	in situ dual enzymatic digestion	876:907	Glycopeptides with desirable peptide length immobilized on a boronate affinity substrate were first prepared as alternative templates through in situ dual enzymatic digestion.
30036038	4	62	theme	glycan-specific	712:726	arg1	MIPs					728:731	glycan-specific MIPs	712:731	glycan-specific MIPs	712:731	Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs.
30036038	11	63	theme	MIPs	1588:1591	arg1	preparation					1557:1567	the facile preparation	1546:1567	the facile preparation of glycan-specific MIPs	1546:1591	This strategy opened a new avenue for the facile preparation of glycan-specific MIPs, facilitating glycan-related applications and research.
30036038	4	64	theme	imprinting	643:652	arg1	strategy					623:630	a new strategy	617:630	a new strategy	617:630	Herein, we report a new strategy, precision imprinting with alternative templates, for the facile preparation of glycan-specific MIPs.
30036038	0	65	theme	Glycan-Specific	64:78	arg1	Antibodies					91:100	Glycan-Specific Artificial Antibodies	64:100	Glycan-Specific Artificial Antibodies	64:100	Precision Imprinting of Glycopeptides for Facile Preparation of Glycan-Specific Artificial Antibodies.
30036038	6	66	theme	appropriate	967:977	arg1	thickness					979:987	an appropriate thickness	964:987	an appropriate thickness through precision imprinting	964:1016	A thinlayer was then produced to cover the glycans to an appropriate thickness through precision imprinting.
30036038	7	67	theme	only	1049:1052	arg1	N-glycans					1054:1062	only N-glycans	1049:1062	only N-glycans as well as both N- and O-glycans	1049:1095	With glycoproteins containing only N-glycans as well as both N- and O-glycans as glycan source, this approach was proved to be widely applicable and efficient.
31011158	0	0	theme	plant-based	81:91	arg1	diets					93:97	plant-based diets	81:97	plant-based diets	81:97	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	9	1	theme	sustainable	1592:1602	arg1	practices					1640:1648	sustainable and more cost-effective aquaculture practices	1592:1648	sustainable and more cost-effective aquaculture practices	1592:1648	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	1	2	theme	host	157:160	arg1	health					162:167	host health	157:167	host health	157:167	The gastrointestinal microbiota plays a critical role on host health and metabolism.
31011158	5	3	theme	fish-gut	730:737	arg1	communities					749:759	fish-gut microbial communities	730:759	fish-gut microbial communities	730:759	The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients.
31011158	4	4	theme	most	498:501	arg1	alternatives					523:534	The most obvious sustainable alternatives	494:534	The most obvious sustainable alternatives to fish meal	494:547	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	4	4	theme	most	498:501	arg1	feedstuffs					559:568	plant feedstuffs	553:568	plant feedstuffs	553:568	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	2	5	theme	aquaculture	335:345	arg1	production					347:356	aquaculture production	335:356	aquaculture production	335:356	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	6	6	theme	beneficial	941:950	arg1	strategy					952:959	a beneficial strategy	939:959	a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP	939:1035	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	6	6	theme	beneficial	941:950	arg1	pressure					876:883	a selective pressure	864:883	a selective pressure of plant-based diets	864:904	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	7	7	with	isolates	1073:1080	arg1	activities					1108:1117	diverse carbohydrase activities	1087:1117	diverse carbohydrase activities from the gut of European sea bass	1087:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	0	8	from	Selection	0:8	arg1	gut					53:55	the gut	49:55	the gut of carnivorous fish	49:75	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	7	9	theme	bacterial	1051:1059	arg1	isolates					1073:1080	bacterial sporulating isolates	1051:1080	bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass	1051:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	2	10	theme	necessary	278:286	arg1	enzymes					288:294	the necessary enzymes	274:294	the necessary enzymes	274:294	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	9	11	from	growth	1477:1482	arg1	fish					1519:1522	fish	1519:1522	fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices	1519:1648	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	7	12	theme	bass	1148:1151	arg1	gut					1128:1130	the gut	1124:1130	the gut of European sea bass	1124:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	9	13	theme	select	1444:1449	arg1	isolates					1451:1458	the select isolates	1440:1458	the select isolates	1440:1458	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	7	14	theme	sporulating	1061:1071	arg1	isolates					1073:1080	bacterial sporulating isolates	1051:1080	bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass	1051:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	7	15	theme	probiotic	1190:1198	arg1	potential					1200:1208	high probiotic potential	1185:1208	high probiotic potential	1185:1208	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	3	16	theme	pollutants	482:491	arg1	meal					425:428	fish meal	420:428	fish meal	420:428	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	16	theme	pollutants	482:491	arg1	commodity					448:456	an unsustainable commodity	431:456	an unsustainable commodity	431:456	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	16	theme	pollutants	482:491	arg1	source					464:469	a source	462:469	a source of organic pollutants	462:491	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	2	17	from	nutrition	227:235	arg1	important					206:214	important	206:214	important	206:214	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	2	18	contain	possess	258:264	arg2	some					266:269	some	266:269	some	266:269	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	2	18	contain	possess	258:264	arg2	enzymes					288:294	the necessary enzymes	274:294	the necessary enzymes	274:294	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	2	18	contain	possess	258:264	arg1	fish					246:249	fish	246:249	fish	246:249	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	7	19	theme	sea	1144:1146	arg1	bass					1148:1151	European sea bass	1135:1151	European sea bass	1135:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	0	20	from	gut	53:55	arg1	Selection					0:8	Selection	0:8	Selection of carbohydrate-active probiotics from the gut of carnivorous fish	0:75	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	0	20	from	gut	53:55	arg1	probiotics					33:42	carbohydrate-active probiotics	13:42	carbohydrate-active probiotics from the gut of carnivorous fish	13:75	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	9	21	theme	aquaculture	1628:1638	arg1	practices					1640:1648	sustainable and more cost-effective aquaculture practices	1592:1648	sustainable and more cost-effective aquaculture practices	1592:1648	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	6	22	theme	dietary	1025:1031	arg1	NSP					1033:1035	dietary NSP	1025:1035	dietary NSP	1025:1035	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	4	23	theme	levels	632:637	arg1	presence					615:622	the presence	611:622	the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish	611:708	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	2	24	from	important	206:214	arg1	nutrition					227:235	teleost nutrition	219:235	teleost nutrition	219:235	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	7	25	theme	European	1135:1142	arg1	bass					1148:1151	European sea bass	1135:1151	European sea bass	1135:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	4	26	theme	high	627:630	arg1	levels					632:637	high levels	627:637	high levels of non-starch polysaccharides (NSP), which are not metabolized by fish	627:708	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	8	27	theme	fish	1252:1255	arg1	gut					1257:1259	the fish gut	1248:1259	the fish gut	1248:1259	By inferring the adaptive fitness to the fish gut and the amenability to industrial processing, we identified the best two candidates to become industrially valuable probiotics.
31011158	6	28	from	strategy	952:959	arg1	microbiota					918:927	fish gut microbiota	909:927	fish gut microbiota	909:927	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	9	29	theme	utilization	1493:1503	arg1	efficiency					1505:1514	feed utilization efficiency	1488:1514	feed utilization efficiency	1488:1514	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	7	30	from	gut	1128:1130	arg1	activities					1108:1117	diverse carbohydrase activities	1087:1117	diverse carbohydrase activities from the gut of European sea bass	1087:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	4	31	theme	non-starch	642:651	arg1	NSP					670:672	NSP	670:672	NSP	670:672	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	4	31	theme	non-starch	642:651	arg1	polysaccharides					653:667	non-starch polysaccharides	642:667	non-starch polysaccharides (NSP)	642:673	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	3	32	theme	fish	384:387	arg1	nutrition					389:397	fish nutrition	384:397	fish nutrition	384:397	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	5	33	theme	different	814:822	arg1	ingredients					824:834	fed different ingredients	810:834	fed different ingredients	810:834	The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients.
31011158	5	33	theme	different	814:822	arg1	host					802:805	the host	798:805	the host	798:805	The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients.
31011158	3	34	theme	fish	420:423	arg1	meal					425:428	fish meal	420:428	fish meal	420:428	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	34	theme	fish	420:423	arg1	commodity					448:456	an unsustainable commodity	431:456	an unsustainable commodity	431:456	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	34	theme	fish	420:423	arg1	source					464:469	a source	462:469	a source of organic pollutants	462:491	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	0	35	theme	probiotics	33:42	arg1	Selection					0:8	Selection	0:8	Selection of carbohydrate-active probiotics from the gut of carnivorous fish	0:75	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	4	36	theme	fish	539:542	arg1	meal					544:547	fish meal	539:547	fish meal	539:547	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	6	37	with	enrichment	968:977	arg1	secretome					998:1006	a secretome	996:1006	a secretome able to mobilize dietary NSP	996:1035	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	8	38	theme	best	1325:1328	arg1	candidates					1334:1343	two candidates	1330:1343	the best two candidates	1321:1343	By inferring the adaptive fitness to the fish gut and the amenability to industrial processing, we identified the best two candidates to become industrially valuable probiotics.
31011158	0	39	theme	carbohydrate-active	13:31	arg1	probiotics					33:42	carbohydrate-active probiotics	13:42	carbohydrate-active probiotics from the gut of carnivorous fish	13:75	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	4	40	theme	plant	553:557	arg1	alternatives					523:534	The most obvious sustainable alternatives	494:534	The most obvious sustainable alternatives to fish meal	494:547	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	4	40	theme	plant	553:557	arg1	feedstuffs					559:568	plant feedstuffs	553:568	plant feedstuffs	553:568	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	1	41	theme	gastrointestinal	104:119	arg1	microbiota					121:130	The gastrointestinal microbiota	100:130	The gastrointestinal microbiota	100:130	The gastrointestinal microbiota plays a critical role on host health and metabolism.
31011158	9	42	theme	isolates	1451:1458	arg1	one					1433:1435	one	1433:1435	one	1433:1435	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	9	42	theme	isolates	1451:1458	arg1	isolates					1451:1458	the select isolates	1440:1458	the select isolates	1440:1458	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	5	43	theme	microbial	739:747	arg1	communities					749:759	fish-gut microbial communities	730:759	fish-gut microbial communities	730:759	The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients.
31011158	6	44	theme	gut	914:916	arg1	microbiota					918:927	fish gut microbiota	909:927	fish gut microbiota	909:927	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	6	45	theme	able	1008:1011	arg1	secretome					998:1006	a secretome	996:1006	a secretome able to mobilize dietary NSP	996:1035	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	8	46	theme	adaptive	1228:1235	arg1	fitness					1237:1243	the adaptive fitness	1224:1243	the adaptive fitness to the fish gut	1224:1259	By inferring the adaptive fitness to the fish gut and the amenability to industrial processing, we identified the best two candidates to become industrially valuable probiotics.
31011158	5	47	theme	communities	749:759	arg1	composition					715:725	The composition	711:725	The composition of fish-gut microbial communities	711:759	The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients.
31011158	4	48	theme	sustainable	511:521	arg1	alternatives					523:534	The most obvious sustainable alternatives	494:534	The most obvious sustainable alternatives to fish meal	494:547	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	4	48	theme	sustainable	511:521	arg1	feedstuffs					559:568	plant feedstuffs	553:568	plant feedstuffs	553:568	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	3	49	theme	main	361:364	arg1	difficulty					366:375	A main difficulty	359:375	A main difficulty within fish nutrition	359:397	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	49	theme	main	361:364	arg1	dependence					406:415	its dependence	402:415	its dependence on fish meal, an unsustainable commodity and a source of organic pollutants	402:491	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	50	theme	unsustainable	434:446	arg1	meal					425:428	fish meal	420:428	fish meal	420:428	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	50	theme	unsustainable	434:446	arg1	commodity					448:456	an unsustainable commodity	431:456	an unsustainable commodity	431:456	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	7	51	theme	diverse	1087:1093	arg1	activities					1108:1117	diverse carbohydrase activities	1087:1117	diverse carbohydrase activities from the gut of European sea bass	1087:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	4	52	theme	obvious	503:509	arg1	alternatives					523:534	The most obvious sustainable alternatives	494:534	The most obvious sustainable alternatives to fish meal	494:547	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	4	52	theme	obvious	503:509	arg1	feedstuffs					559:568	plant feedstuffs	553:568	plant feedstuffs	553:568	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	6	53	theme	bacteria	982:989	arg1	enrichment					968:977	an enrichment	965:977	an enrichment of bacteria with a secretome able to mobilize dietary NSP	965:1035	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	9	54	theme	plant-based	1551:1561	arg1	diets					1563:1567	probiotic-supplemented plant-based diets	1528:1567	probiotic-supplemented plant-based diets	1528:1567	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	3	55	from	dependence	406:415	arg1	meal					425:428	fish meal	420:428	fish meal	420:428	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	55	from	dependence	406:415	arg1	commodity					448:456	an unsustainable commodity	431:456	an unsustainable commodity	431:456	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	3	55	from	dependence	406:415	arg1	source					464:469	a source	462:469	a source of organic pollutants	462:491	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	6	56	theme	diets	900:904	arg1	strategy					952:959	a beneficial strategy	939:959	a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP	939:1035	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	6	56	theme	diets	900:904	arg1	pressure					876:883	a selective pressure	864:883	a selective pressure of plant-based diets	864:904	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	6	57	theme	selective	866:874	arg1	strategy					952:959	a beneficial strategy	939:959	a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP	939:1035	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	6	57	theme	selective	866:874	arg1	pressure					876:883	a selective pressure	864:883	a selective pressure of plant-based diets	864:904	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	2	58	theme	teleost	219:225	arg1	nutrition					227:235	teleost nutrition	219:235	teleost nutrition	219:235	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	9	59	theme	cost-effective	1613:1626	arg1	practices					1640:1648	sustainable and more cost-effective aquaculture practices	1592:1648	sustainable and more cost-effective aquaculture practices	1592:1648	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	3	60	theme	organic	474:480	arg1	pollutants					482:491	organic pollutants	474:491	organic pollutants	474:491	A main difficulty within fish nutrition is its dependence on fish meal, an unsustainable commodity and a source of organic pollutants.
31011158	6	61	theme	plant-based	888:898	arg1	diets					900:904	plant-based diets	888:904	plant-based diets	888:904	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	6	62	theme	fish	909:912	arg1	microbiota					918:927	fish gut microbiota	909:927	fish gut microbiota	909:927	Thus, we hypothesized that a selective pressure of plant-based diets on fish gut microbiota, could be a beneficial strategy for an enrichment of bacteria with a secretome able to mobilize dietary NSP.
31011158	8	63	theme	valuable	1368:1375	arg1	probiotics					1377:1386	industrially valuable probiotics	1355:1386	industrially valuable probiotics	1355:1386	By inferring the adaptive fitness to the fish gut and the amenability to industrial processing, we identified the best two candidates to become industrially valuable probiotics.
31011158	7	64	theme	carbohydrase	1095:1106	arg1	activities					1108:1117	diverse carbohydrase activities	1087:1117	diverse carbohydrase activities from the gut of European sea bass	1087:1151	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	9	65	theme	probiotic-supplemented	1528:1549	arg1	diets					1563:1567	probiotic-supplemented plant-based diets	1528:1567	probiotic-supplemented plant-based diets	1528:1567	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	2	66	theme	dietary	313:319	arg1	challenges					321:330	the dietary challenges	309:330	the dietary challenges of aquaculture production	309:356	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	9	67	theme	feed	1488:1491	arg1	efficiency					1505:1514	feed utilization efficiency	1488:1514	feed utilization efficiency	1488:1514	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	9	68	theme	better	1470:1475	arg1	growth					1477:1482	a better growth	1468:1482	a better growth	1468:1482	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	8	69	theme	industrial	1284:1293	arg1	processing					1295:1304	industrial processing	1284:1304	industrial processing	1284:1304	By inferring the adaptive fitness to the fish gut and the amenability to industrial processing, we identified the best two candidates to become industrially valuable probiotics.
31011158	1	70	theme	critical	140:147	arg1	role					149:152	a critical role	138:152	a critical role	138:152	The gastrointestinal microbiota plays a critical role on host health and metabolism.
31011158	4	71	theme	nutritive	581:589	arg1	value					591:595	their nutritive value	575:595	their nutritive value	575:595	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	0	72	theme	fish	72:75	arg1	gut					53:55	the gut	49:55	the gut of carnivorous fish	49:75	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	5	73	theme	fed	810:812	arg1	ingredients					824:834	fed different ingredients	810:834	fed different ingredients	810:834	The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients.
31011158	5	73	theme	fed	810:812	arg1	host					802:805	the host	798:805	the host	798:805	The composition of fish-gut microbial communities have been demonstrated to adapt when the host is fed different ingredients.
31011158	7	74	with	isolates	1171:1178	arg1	potential					1200:1208	high probiotic potential	1185:1208	high probiotic potential	1185:1208	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
31011158	2	75	theme	production	347:356	arg1	challenges					321:330	the dietary challenges	309:330	the dietary challenges of aquaculture production	309:356	This is particularly important in teleost nutrition, because fish do not possess some of the necessary enzymes to cope with the dietary challenges of aquaculture production.
31011158	9	76	from	efficiency	1505:1514	arg1	fish					1519:1522	fish	1519:1522	fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices	1519:1648	This potential was confirmed in vivo, since one of the select isolates lead to a better growth and feed utilization efficiency in fish fed probiotic-supplemented plant-based diets, thus contributing for sustainable and more cost-effective aquaculture practices.
31011158	0	77	theme	carnivorous	60:70	arg1	fish					72:75	carnivorous fish	60:75	carnivorous fish	60:75	Selection of carbohydrate-active probiotics from the gut of carnivorous fish fed plant-based diets.
31011158	4	78	theme	polysaccharides	653:667	arg1	levels					632:637	high levels	627:637	high levels of non-starch polysaccharides (NSP), which are not metabolized by fish	627:708	The most obvious sustainable alternatives to fish meal are plant feedstuffs, but their nutritive value is limited by the presence of high levels of non-starch polysaccharides (NSP), which are not metabolized by fish.
31011158	7	79	theme	high	1185:1188	arg1	potential					1200:1208	high probiotic potential	1185:1208	high probiotic potential	1185:1208	By targeting bacterial sporulating isolates with diverse carbohydrase activities from the gut of European sea bass, we have obtained isolates with high probiotic potential.
30966526	0	0	theme	Polysaccharide	70:83	arg1	Effect					15:20	Lipid-Lowering Effect	0:20	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.	0:173	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	5	1	contain	has	748:750	arg1	PESF					743:746	PESF	743:746	PESF	743:746	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	5	1	contain	has	748:750	arg1	Meanwhile					732:740	Meanwhile	732:740	Meanwhile	732:740	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	5	1	contain	has	748:750	arg2	toxicity					766:773	no detectable toxicity	752:773	no detectable toxicity	752:773	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	5	2	theme	foam-cell	812:820	arg1	formation					822:830	foam-cell formation	812:830	foam-cell formation	812:830	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	3	3	theme	eryngii	487:493	arg1	polysaccharide					495:508	the P. eryngii polysaccharide	480:508	the P. eryngii polysaccharide	480:508	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	7	4	dep	P.	1084:1085	arg1	eryngii					1087:1093	eryngii	1087:1093	eryngii	1087:1093	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	0	5	from	Effect	15:20	arg1	Models					167:172	Zebrafish Models	157:172	Zebrafish Models	157:172	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	0	5	from	Effect	15:20	arg1	Cells					147:151	Macrophage-Derived Foam Cells	123:151	Macrophage-Derived Foam Cells	123:151	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	0	5	from	Effect	15:20	arg1	Fermentation					102:113	Solid-State Fermentation	90:113	Solid-State Fermentation	90:113	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	5	6	theme	oxidized	881:888	arg1	lipoprotein					902:912	low-density lipoprotein	890:912	oxidized low-density lipoprotein	881:912	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	6	7	theme	absorption	1000:1009	arg1	phase					1011:1015	the lipid absorption phase	990:1015	the lipid absorption phase in a zebrafish hyperlipidemia model	990:1051	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	0	8	theme	Solid-State	90:100	arg1	Fermentation					102:113	Solid-State Fermentation	90:113	Solid-State Fermentation	90:113	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	6	9	theme	lipid	994:998	arg1	phase					1011:1015	the lipid absorption phase	990:1015	the lipid absorption phase in a zebrafish hyperlipidemia model	990:1051	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	2	10	theme	Previous	296:303	arg1	studies					305:311	Previous studies	296:311	Previous studies	296:311	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	1	11	theme	cerebrovascular	270:284	arg1	diseases					286:293	cerebrovascular diseases	270:293	cerebrovascular diseases	270:293	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	7	12	theme	additive	1193:1200	arg1	polysaccharide					1095:1108	the P. eryngii polysaccharide	1080:1108	the P. eryngii polysaccharide from solid-state fermentation (PESF)	1080:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	12	theme	additive	1193:1200	arg1	food					1188:1191	a valuable lipid-lowering food	1162:1191	a valuable lipid-lowering food additive	1162:1200	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	2	13	from	bodies	362:367	arg1	polysaccharides					332:346	polysaccharides	332:346	polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom)	332:418	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	2	14	theme	oyster	403:408	arg1	eryngii					389:395	Pleurotus eryngii	379:395	Pleurotus eryngii (king oyster mushroom)	379:418	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	2	14	theme	oyster	403:408	arg1	mushroom					410:417	king oyster mushroom	398:417	king oyster mushroom	398:417	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	7	15	theme	solid-state	1115:1125	arg1	PESF					1141:1144	PESF	1141:1144	PESF	1141:1144	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	15	theme	solid-state	1115:1125	arg1	fermentation					1127:1138	solid-state fermentation	1115:1138	solid-state fermentation (PESF)	1115:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	3	16	theme	solid-state	525:535	arg1	fermentation					537:548	solid-state fermentation	525:548	solid-state fermentation (PESF)	525:555	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	3	16	theme	solid-state	525:535	arg1	PESF					551:554	PESF	551:554	PESF	551:554	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	2	17	theme	king	398:401	arg1	eryngii					389:395	Pleurotus eryngii	379:395	Pleurotus eryngii (king oyster mushroom)	379:418	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	2	17	theme	king	398:401	arg1	mushroom					410:417	king oyster mushroom	398:417	king oyster mushroom	398:417	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	2	18	theme	lipid	450:454	arg1	content					456:462	the lipid content	446:462	the lipid content	446:462	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	6	19	from	phase	1011:1015	arg1	model					1047:1051	a zebrafish hyperlipidemia model	1020:1051	a zebrafish hyperlipidemia model	1020:1051	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	7	20	theme	lipid-lowering	1173:1186	arg1	polysaccharide					1095:1108	the P. eryngii polysaccharide	1080:1108	the P. eryngii polysaccharide from solid-state fermentation (PESF)	1080:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	20	theme	lipid-lowering	1173:1186	arg1	food					1188:1191	a valuable lipid-lowering food	1162:1191	a valuable lipid-lowering food additive	1162:1200	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	0	21	theme	Lipid-Lowering	0:13	arg1	Effect					15:20	Lipid-Lowering Effect	0:20	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.	0:173	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	5	22	theme	macrophage	842:851	arg1	cells					853:857	murine macrophage cells	835:857	murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein	835:912	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	5	22	theme	macrophage	842:851	arg1	RAW264.7					860:867	RAW264.7	860:867	RAW264.7	860:867	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	3	23	theme	lignocellulosic	563:577	arg1	corn-cobs					587:595	corn-cobs	587:595	corn-cobs	587:595	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	3	23	theme	lignocellulosic	563:577	arg1	bran					607:610	wheat bran	601:610	wheat bran	601:610	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	3	23	theme	lignocellulosic	563:577	arg1	wastes					579:584	lignocellulosic wastes	563:584	lignocellulosic wastes	563:584	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	2	24	theme	eryngii	389:395	arg1	bodies					362:367	fruiting bodies	353:367	fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom)	353:418	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	2	24	theme	eryngii	389:395	arg1	PEPE					370:373	PEPE	370:373	PEPE	370:373	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	0	25	theme	Macrophage-Derived	123:140	arg1	Cells					147:151	Macrophage-Derived Foam Cells	123:151	Macrophage-Derived Foam Cells	123:151	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	1	26	theme	risk	199:202	arg1	factor					204:209	a key risk factor	193:209	a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases	193:293	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	1	26	theme	risk	199:202	arg1	Hyperlipidemia					175:188	Hyperlipidemia	175:188	Hyperlipidemia	175:188	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	7	27	theme	valuable	1164:1171	arg1	polysaccharide					1095:1108	the P. eryngii polysaccharide	1080:1108	the P. eryngii polysaccharide from solid-state fermentation (PESF)	1080:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	27	theme	valuable	1164:1171	arg1	food					1188:1191	a valuable lipid-lowering food	1162:1191	a valuable lipid-lowering food additive	1162:1200	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	6	28	theme	lipid-lowering	960:973	arg1	effects					975:981	lipid-lowering effects	960:981	lipid-lowering effects	960:981	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	7	29	theme	P.	1084:1085	arg1	materials					1209:1217	raw materials	1205:1217	raw materials	1205:1217	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	29	theme	P.	1084:1085	arg1	polysaccharide					1095:1108	the P. eryngii polysaccharide	1080:1108	the P. eryngii polysaccharide from solid-state fermentation (PESF)	1080:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	29	theme	P.	1084:1085	arg1	food					1188:1191	a valuable lipid-lowering food	1162:1191	a valuable lipid-lowering food additive	1162:1200	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	4	30	theme	high-performance	617:632	arg1	chromatography					641:654	high-performance liquid chromatography	617:654	The high-performance liquid chromatography (HPLC) assays	613:668	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	4	30	theme	high-performance	617:632	arg1	HPLC					657:660	HPLC	657:660	HPLC	657:660	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	5	31	theme	detectable	755:764	arg1	toxicity					766:773	no detectable toxicity	752:773	no detectable toxicity	752:773	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	4	32	theme	similar	695:701	arg1	composition					703:713	a similar composition	693:713	a similar composition to that of PEPE	693:729	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	6	33	contain	has	956:958	arg1	PESF					951:954	PESF	951:954	PESF	951:954	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	6	33	contain	has	956:958	arg2	effects					975:981	lipid-lowering effects	960:981	lipid-lowering effects	960:981	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	1	34	theme	key	195:197	arg1	factor					204:209	a key risk factor	193:209	a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases	193:293	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	1	34	theme	key	195:197	arg1	Hyperlipidemia					175:188	Hyperlipidemia	175:188	Hyperlipidemia	175:188	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	0	35	theme	Pleurotus	29:37	arg1	Polysaccharide					70:83	the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide	25:83	the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation	25:113	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	7	36	from	fermentation	1127:1138	arg1	materials					1209:1217	raw materials	1205:1217	raw materials	1205:1217	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	36	from	fermentation	1127:1138	arg1	polysaccharide					1095:1108	the P. eryngii polysaccharide	1080:1108	the P. eryngii polysaccharide from solid-state fermentation (PESF)	1080:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	36	from	fermentation	1127:1138	arg1	food					1188:1191	a valuable lipid-lowering food	1162:1191	a valuable lipid-lowering food additive	1162:1200	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	0	37	theme	Foam	142:145	arg1	Cells					147:151	Macrophage-Derived Foam Cells	123:151	Macrophage-Derived Foam Cells	123:151	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	5	38	theme	murine	835:840	arg1	cells					853:857	murine macrophage cells	835:857	murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein	835:912	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	5	38	theme	murine	835:840	arg1	RAW264.7					860:867	RAW264.7	860:867	RAW264.7	860:867	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	1	39	theme	inducing	214:221	arg1	liver					229:233	inducing fatty liver	214:233	inducing fatty liver	214:233	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	0	40	theme	King	48:51	arg1	Mushroom					60:67	King Oyster Mushroom	48:67	King Oyster Mushroom	48:67	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	7	41	theme	raw	1205:1207	arg1	materials					1209:1217	raw materials	1205:1217	raw materials	1205:1217	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	41	theme	raw	1205:1207	arg1	polysaccharide					1095:1108	the P. eryngii polysaccharide	1080:1108	the P. eryngii polysaccharide from solid-state fermentation (PESF)	1080:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	0	42	theme	Zebrafish	157:165	arg1	Models					167:172	Zebrafish Models	157:172	Zebrafish Models	157:172	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	5	43	theme	low-density	890:900	arg1	lipoprotein					902:912	low-density lipoprotein	890:912	oxidized low-density lipoprotein	881:912	Meanwhile, PESF has no detectable toxicity and is able to significantly inhibit foam-cell formation in murine macrophage cells (RAW264.7) induced by oxidized low-density lipoprotein.
30966526	6	44	theme	Further	915:921	arg1	verification					923:934	Further verification	915:934	Further verification	915:934	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	0	45	dep	Pleurotus	29:37	arg1	eryngii					39:45	eryngii	39:45	eryngii	39:45	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	0	45	dep	Pleurotus	29:37	arg1	Mushroom					60:67	King Oyster Mushroom	48:67	King Oyster Mushroom	48:67	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	3	46	theme	P.	484:485	arg1	polysaccharide					495:508	the P. eryngii polysaccharide	480:508	the P. eryngii polysaccharide	480:508	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	0	47	from	Fermentation	102:113	arg1	Polysaccharide					70:83	the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide	25:83	the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation	25:113	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	0	47	from	Fermentation	102:113	arg1	Effect					15:20	Lipid-Lowering Effect	0:20	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.	0:173	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	1	48	from	factor	204:209	arg1	atherosclerosis					250:264	atherosclerosis	250:264	atherosclerosis	250:264	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	1	48	from	factor	204:209	arg1	diseases					286:293	cerebrovascular diseases	270:293	cerebrovascular diseases	270:293	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	1	48	from	factor	204:209	arg1	hypertension					236:247	hypertension	236:247	hypertension	236:247	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	1	48	from	factor	204:209	arg1	liver					229:233	inducing fatty liver	214:233	inducing fatty liver	214:233	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	2	49	theme	fruiting	353:360	arg1	bodies					362:367	fruiting bodies	353:367	fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom)	353:418	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	2	49	theme	fruiting	353:360	arg1	PEPE					370:373	PEPE	370:373	PEPE	370:373	Previous studies have verified that polysaccharides from fruiting bodies (PEPE) of Pleurotus eryngii (king oyster mushroom) are capable of decreasing the lipid content.
30966526	1	50	theme	fatty	223:227	arg1	liver					229:233	inducing fatty liver	214:233	inducing fatty liver	214:233	Hyperlipidemia is a key risk factor in inducing fatty liver, hypertension, atherosclerosis and cerebrovascular diseases.
30966526	7	51	used	used	1154:1157	arg2	food					1188:1191	a valuable lipid-lowering food	1162:1191	a valuable lipid-lowering food additive	1162:1200	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	51	used	used	1154:1157	arg2	materials					1209:1217	raw materials	1205:1217	raw materials	1205:1217	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	7	51	used	used	1154:1157	arg2	polysaccharide					1095:1108	the P. eryngii polysaccharide	1080:1108	the P. eryngii polysaccharide from solid-state fermentation (PESF)	1080:1145	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	6	52	theme	zebrafish	1022:1030	arg1	model					1047:1051	a zebrafish hyperlipidemia model	1020:1051	a zebrafish hyperlipidemia model	1020:1051	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30966526	7	53	theme	lipid-lowering	1233:1246	arg1	drugs					1248:1252	lipid-lowering drugs	1233:1252	lipid-lowering drugs	1233:1252	Our findings suggest that the P. eryngii polysaccharide from solid-state fermentation (PESF) can be used as a valuable lipid-lowering food additive or raw materials for producing lipid-lowering drugs.
30966526	4	54	theme	chromatography	641:654	arg1	assays					663:668	The high-performance liquid chromatography (HPLC) assays	613:668	The high-performance liquid chromatography (HPLC) assays	613:668	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	3	55	theme	wheat	601:605	arg1	bran					607:610	wheat bran	601:610	wheat bran	601:610	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	3	55	theme	wheat	601:605	arg1	wastes					579:584	lignocellulosic wastes	563:584	lignocellulosic wastes	563:584	In this study, the P. eryngii polysaccharide is obtained by solid-state fermentation (PESF) using lignocellulosic wastes, corn-cobs and wheat bran.
30966526	4	56	theme	liquid	634:639	arg1	chromatography					641:654	high-performance liquid chromatography	617:654	The high-performance liquid chromatography (HPLC) assays	613:668	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	4	56	theme	liquid	634:639	arg1	HPLC					657:660	HPLC	657:660	HPLC	657:660	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	0	57	theme	Oyster	53:58	arg1	Mushroom					60:67	King Oyster Mushroom	48:67	King Oyster Mushroom	48:67	Lipid-Lowering Effect of the Pleurotus eryngii (King Oyster Mushroom) Polysaccharide from Solid-State Fermentation on Both Macrophage-Derived Foam Cells and Zebrafish Models.
30966526	4	58	contain	has	689:691	arg2	composition					703:713	a similar composition	693:713	a similar composition to that of PEPE	693:729	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	4	58	contain	has	689:691	arg1	PESF					684:687	PESF	684:687	PESF	684:687	The high-performance liquid chromatography (HPLC) assays indicate that PESF has a similar composition to that of PEPE.
30966526	6	59	theme	hyperlipidemia	1032:1045	arg1	model					1047:1051	a zebrafish hyperlipidemia model	1020:1051	a zebrafish hyperlipidemia model	1020:1051	Further verification indicates that PESF has lipid-lowering effects during the lipid absorption phase in a zebrafish hyperlipidemia model.
30404931	9	0	theme	export	1120:1125	arg1	LES					1137:1139	LES	1137:1139	LES	1137:1139	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	9	0	theme	export	1120:1125	arg1	sequence					1127:1134	a lipoprotein export sequence	1106:1134	a lipoprotein export sequence (LES)	1106:1140	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	15	1	theme	breakdown	2241:2249	arg1	products					2251:2258	polysaccharide breakdown products	2226:2258	polysaccharide breakdown products	2226:2258	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	15	2	theme	bacterial	2194:2202	arg1	species					2204:2210	other bacterial species	2188:2210	other bacterial species	2188:2210	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	16	3	theme	rich	2338:2341	arg1	acid					2349:2352	a negatively charged rich amino acid	2317:2352	a negatively charged rich amino acid motif (LES)	2317:2364	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	8	4	theme	split	917:921	arg1	localization					923:934	a split localization	915:934	a split localization	915:934	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	13	5	theme	OMVs	1657:1660	arg1	role					1649:1652	the role	1645:1652	the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota	1645:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	6	theme	microbiota	1845:1854	arg1	Species					1769:1775	different metabolic capabilities.IMPORTANCE Species	1725:1775	different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus	1725:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	6	theme	microbiota	1845:1854	arg1	members					1820:1826	predominant members	1808:1826	predominant members of the human gut microbiota	1808:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	7	7	theme	sus	819:821	arg1	operon					823:828	the sus operon	815:828	the sus operon	815:828	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	16	8	theme	acid	2349:2352	arg1	motif					2354:2358	a negatively charged rich amino acid motif	2317:2358	a negatively charged rich amino acid motif (LES)	2317:2364	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	16	8	theme	acid	2349:2352	arg1	LES					2361:2363	LES	2361:2363	LES	2361:2363	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	13	9	theme	predominant	1808:1818	arg1	Species					1769:1775	different metabolic capabilities.IMPORTANCE Species	1725:1775	different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus	1725:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	9	theme	predominant	1808:1818	arg1	members					1820:1826	predominant members	1808:1826	predominant members of the human gut microbiota	1808:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	12	10	theme	carbon	1610:1615	arg1	source					1617:1622	the only carbon source	1601:1622	the only carbon source	1601:1622	We also show that surface-exposed SusG in OMVs is active and rescues the growth of bacterial cells incapable of growing on starch as the only carbon source.
30404931	15	11	theme	enzymatic	2049:2057	arg1	activities					2059:2068	many enzymatic activities	2044:2068	many enzymatic activities involved in the cleavage of complex polysaccharides	2044:2120	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	8	12	from	OMVs	982:985	arg1	SusG					955:958	the alpha-amylase SusG	937:958	the alpha-amylase SusG	937:958	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	8	12	from	OMVs	982:985	arg1	enriched					970:977	enriched	970:977	enriched	970:977	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	13	13	theme	human	1835:1839	arg1	microbiota					1845:1854	the human gut microbiota	1831:1854	the human gut microbiota	1831:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	8	14	from	enriched	970:977	arg1	OMVs					982:985	OMVs	982:985	OMVs	982:985	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	17	15	theme	Bacteroides	2530:2540	arg1	lipoproteins					2542:2553	Bacteroides lipoproteins	2530:2553	Bacteroides lipoproteins	2530:2553	Our findings strongly suggest that surface exposure is coupled to packing of Bacteroides lipoproteins into OMVs.
30404931	5	16	theme	thetaiotaomicron	511:526	arg1	OMVs					528:531	Bacteroides thetaiotaomicron OMVs	499:531	Bacteroides thetaiotaomicron OMVs	499:531	Here, we revisited the protein composition of Bacteroides thetaiotaomicron OMVs by mass spectrometry.
30404931	14	17	from	disease	2024:2030	arg1	protection					2008:2017	protection	2008:2017	protection from disease	2008:2030	OMVs in Bacteroides have been shown to be important for the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease.
30404931	14	17	from	disease	2024:2030	arg1	tolerance					1994:2002	immune tolerance	1987:2002	immune tolerance	1987:2002	OMVs in Bacteroides have been shown to be important for the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease.
30404931	3	18	theme	gut	289:291	arg1	microbiota					293:302	the human gut microbiota	279:302	the human gut microbiota	279:302	are prominent components of the human gut microbiota, and OMVs produced by these species are proposed to play key roles in gut homeostasis.
30404931	4	19	from	biogenesis	395:404	arg1	Bacteroides					409:419	Bacteroides	409:419	Bacteroides	409:419	OMV biogenesis in Bacteroides is a poorly understood process.
30404931	15	20	theme	products	2251:2258	arg1	release					2215:2221	release	2215:2221	release of polysaccharide breakdown products into the gut lumen	2215:2277	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	1	21	theme	membrane	118:125	arg1	vesicles					127:134	Outer membrane vesicles	112:134	Outer membrane vesicles (OMVs)	112:141	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	21	theme	membrane	118:125	arg1	structures					157:166	spherical structures	147:166	spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria	147:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	21	theme	membrane	118:125	arg1	OMVs					137:140	OMVs	137:140	OMVs	137:140	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	6	22	contain	contain	604:610	arg1	OMVs					573:576	OMVs	573:576	OMVs produced by this organism	573:602	We confirmed that OMVs produced by this organism contain large quantities of glycosidases and proteases, with most of them being lipoproteins.
30404931	6	22	contain	contain	604:610	arg2	quantities					618:627	large quantities	612:627	large quantities of glycosidases and proteases	612:657	We confirmed that OMVs produced by this organism contain large quantities of glycosidases and proteases, with most of them being lipoproteins.
30404931	13	23	theme	gut	1841:1843	arg1	microbiota					1845:1854	the human gut microbiota	1831:1854	the human gut microbiota	1831:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	24	theme	Bacteroides	1786:1796	arg1	genus					1798:1802	the Bacteroides genus	1782:1802	the Bacteroides genus	1782:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	17	25	theme	surface	2488:2494	arg1	exposure					2496:2503	surface exposure	2488:2503	surface exposure	2488:2503	Our findings strongly suggest that surface exposure is coupled to packing of Bacteroides lipoproteins into OMVs.
30404931	15	26	theme	polysaccharide	2226:2239	arg1	products					2251:2258	polysaccharide breakdown products	2226:2258	polysaccharide breakdown products	2226:2258	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	5	27	theme	protein	476:482	arg1	composition					484:494	the protein composition	472:494	the protein composition of Bacteroides thetaiotaomicron OMVs	472:531	Here, we revisited the protein composition of Bacteroides thetaiotaomicron OMVs by mass spectrometry.
30404931	15	28	theme	polysaccharides	2106:2120	arg1	cleavage					2086:2093	the cleavage	2082:2093	the cleavage of complex polysaccharides	2082:2120	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	12	29	theme	only	1605:1608	arg1	source					1617:1622	the only carbon source	1601:1622	the only carbon source	1601:1622	We also show that surface-exposed SusG in OMVs is active and rescues the growth of bacterial cells incapable of growing on starch as the only carbon source.
30404931	16	30	theme	surface-exposed	2407:2421	arg1	SusG					2437:2440	the surface-exposed alpha-amylase SusG	2403:2440	the surface-exposed alpha-amylase SusG into OMVs	2403:2450	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	0	31	from	Processes	86:94	arg1	Bacteroides					99:109	Bacteroides	99:109	Bacteroides	99:109	Surface Exposure and Packing of Lipoproteins into Outer Membrane Vesicles Are Coupled Processes in Bacteroides.
30404931	6	32	theme	glycosidases	632:643	arg1	quantities					618:627	large quantities	612:627	large quantities of glycosidases and proteases	612:657	We confirmed that OMVs produced by this organism contain large quantities of glycosidases and proteases, with most of them being lipoproteins.
30404931	0	33	theme	Membrane	56:63	arg1	Vesicles					65:72	Outer Membrane Vesicles	50:72	Outer Membrane Vesicles	50:72	Surface Exposure and Packing of Lipoproteins into Outer Membrane Vesicles Are Coupled Processes in Bacteroides.
30404931	16	34	theme	SusG	2437:2440	arg1	packing					2392:2398	efficient packing	2382:2398	efficient packing of the surface-exposed alpha-amylase SusG into OMVs	2382:2450	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	13	35	theme	capabilities.IMPORTANCE	1745:1767	arg1	Species					1769:1775	different metabolic capabilities.IMPORTANCE Species	1725:1775	different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus	1725:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	35	theme	capabilities.IMPORTANCE	1745:1767	arg1	members					1820:1826	predominant members	1808:1826	predominant members of the human gut microbiota	1808:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	9	36	theme	periplasmic	1212:1222	arg1	face					1224:1227	the periplasmic face	1208:1227	the periplasmic face of the OM	1208:1237	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	1	37	theme	spherical	147:155	arg1	vesicles					127:134	Outer membrane vesicles	112:134	Outer membrane vesicles (OMVs)	112:141	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	37	theme	spherical	147:155	arg1	structures					157:166	spherical structures	147:166	spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria	147:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	10	38	theme	SusG	1353:1356	arg1	exposure					1325:1332	surface exposure	1317:1332	surface exposure	1317:1332	Mutations in the LES motif caused defects in surface exposure and recruitment of SusG into OMVs.
30404931	10	38	theme	SusG	1353:1356	arg1	recruitment					1338:1348	recruitment	1338:1348	recruitment of SusG into OMVs	1338:1366	Mutations in the LES motif caused defects in surface exposure and recruitment of SusG into OMVs.
30404931	18	39	theme	probiotic	2622:2630	arg1	interventions					2632:2644	tailor-made probiotic interventions	2610:2644	tailor-made probiotic interventions	2610:2644	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	4	40	theme	understood	433:442	arg1	biogenesis					395:404	OMV biogenesis	391:404	OMV biogenesis in Bacteroides	391:419	OMV biogenesis in Bacteroides is a poorly understood process.
30404931	4	40	theme	understood	433:442	arg1	process					444:450	a poorly understood process	424:450	a poorly understood process	424:450	OMV biogenesis in Bacteroides is a poorly understood process.
30404931	14	41	theme	immune	1987:1992	arg1	tolerance					1994:2002	immune tolerance	1987:2002	immune tolerance	1987:2002	OMVs in Bacteroides have been shown to be important for the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease.
30404931	9	42	theme	OM	1236:1237	arg1	face					1224:1227	the periplasmic face	1208:1227	the periplasmic face of the OM	1208:1237	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	12	43	theme	cells	1561:1565	arg1	growth					1541:1546	the growth	1537:1546	the growth of bacterial cells incapable of growing on starch as the only carbon source	1537:1622	We also show that surface-exposed SusG in OMVs is active and rescues the growth of bacterial cells incapable of growing on starch as the only carbon source.
30404931	18	44	theme	interventions	2632:2644	arg1	generation					2596:2605	the generation	2592:2605	the generation of tailor-made probiotic interventions	2592:2644	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	13	45	theme	different	1725:1733	arg1	Species					1769:1775	different metabolic capabilities.IMPORTANCE Species	1725:1775	different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus	1725:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	45	theme	different	1725:1733	arg1	members					1820:1826	predominant members	1808:1826	predominant members of the human gut microbiota	1808:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	0	46	theme	Surface	0:6	arg1	Exposure					8:15	Surface Exposure	0:15	Surface Exposure	0:15	Surface Exposure and Packing of Lipoproteins into Outer Membrane Vesicles Are Coupled Processes in Bacteroides.
30404931	8	47	theme	oligosaccharide	998:1012	arg1	SusC					1023:1026	the oligosaccharide importer SusC	994:1026	the oligosaccharide importer SusC	994:1026	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	14	48	theme	relationships	1955:1967	arg1	homeostasis					1917:1927	the homeostasis	1913:1927	the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease	1913:2030	OMVs in Bacteroides have been shown to be important for the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease.
30404931	7	49	theme	polysaccharide	767:780	arg1	PULs					800:803	PULs	800:803	PULs	800:803	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	7	49	theme	polysaccharide	767:780	arg1	loci					794:797	polysaccharide utilization loci	767:797	polysaccharide utilization loci (PULs)	767:804	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	7	49	theme	polysaccharide	767:780	arg1	operon					823:828	the sus operon	815:828	the sus operon	815:828	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	6	50	theme	large	612:616	arg1	quantities					618:627	large quantities	612:627	large quantities of glycosidases and proteases	612:657	We confirmed that OMVs produced by this organism contain large quantities of glycosidases and proteases, with most of them being lipoproteins.
30404931	10	51	from	Mutations	1272:1280	arg1	motif					1293:1297	the LES motif	1285:1297	the LES motif	1285:1297	Mutations in the LES motif caused defects in surface exposure and recruitment of SusG into OMVs.
30404931	3	52	theme	gut	374:376	arg1	homeostasis					378:388	gut homeostasis	374:388	gut homeostasis	374:388	are prominent components of the human gut microbiota, and OMVs produced by these species are proposed to play key roles in gut homeostasis.
30404931	14	53	theme	complex	1932:1938	arg1	relationships					1955:1967	complex host-commensal relationships	1932:1967	complex host-commensal relationships	1932:1967	OMVs in Bacteroides have been shown to be important for the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease.
30404931	6	54	theme	proteases	649:657	arg1	quantities					618:627	large quantities	612:627	large quantities of glycosidases and proteases	612:657	We confirmed that OMVs produced by this organism contain large quantities of glycosidases and proteases, with most of them being lipoproteins.
30404931	12	55	from	SusG	1502:1505	arg1	OMVs					1510:1513	OMVs	1510:1513	OMVs	1510:1513	We also show that surface-exposed SusG in OMVs is active and rescues the growth of bacterial cells incapable of growing on starch as the only carbon source.
30404931	15	56	contain	carry	2038:2042	arg1	OMVs					2033:2036	OMVs	2033:2036	OMVs	2033:2036	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	15	56	contain	carry	2038:2042	arg2	activities					2059:2068	many enzymatic activities	2044:2068	many enzymatic activities involved in the cleavage of complex polysaccharides	2044:2120	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	15	56	contain	carry	2038:2042	arg1	goods					2155:2159	public goods	2148:2159	public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen	2148:2277	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	18	57	theme	Bacteroides	2697:2707	arg1	strains					2709:2715	Bacteroides strains	2697:2715	Bacteroides strains displaying proteins of interest in OMVs	2697:2755	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	9	58	contain	possess	1098:1104	arg2	LES					1137:1139	LES	1137:1139	LES	1137:1139	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	9	58	contain	possess	1098:1104	arg2	sequence					1127:1134	a lipoprotein export sequence	1106:1134	a lipoprotein export sequence (LES)	1106:1140	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	9	58	contain	possess	1098:1104	arg1	lipoproteins					1085:1096	all OMV-enriched lipoproteins	1068:1096	all OMV-enriched lipoproteins	1068:1096	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	8	59	theme	Sus	894:896	arg1	system					898:903	the Sus system	890:903	the Sus system	890:903	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	9	60	theme	OMV-enriched	1072:1083	arg1	lipoproteins					1085:1096	all OMV-enriched lipoproteins	1068:1096	all OMV-enriched lipoproteins	1068:1096	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	10	61	from	defects	1306:1312	arg1	exposure					1325:1332	surface exposure	1317:1332	surface exposure	1317:1332	Mutations in the LES motif caused defects in surface exposure and recruitment of SusG into OMVs.
30404931	10	61	from	defects	1306:1312	arg1	recruitment					1338:1348	recruitment	1338:1348	recruitment of SusG into OMVs	1338:1366	Mutations in the LES motif caused defects in surface exposure and recruitment of SusG into OMVs.
30404931	13	62	theme	public	1666:1671	arg1	goods					1673:1677	public goods	1666:1677	"public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota	1665:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	63	theme	metabolic	1735:1743	arg1	Species					1769:1775	different metabolic capabilities.IMPORTANCE Species	1725:1775	different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus	1725:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	63	theme	metabolic	1735:1743	arg1	members					1820:1826	predominant members	1808:1826	predominant members of the human gut microbiota	1808:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	1	64	theme	Gram-negative	210:222	arg1	bacteria					224:231	Gram-negative bacteria	210:231	Gram-negative bacteria	210:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	16	65	theme	charged	2330:2336	arg1	acid					2349:2352	a negatively charged rich amino acid	2317:2352	a negatively charged rich amino acid motif (LES)	2317:2364	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	9	66	theme	lipoprotein	1108:1118	arg1	LES					1137:1139	LES	1137:1139	LES	1137:1139	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	9	66	theme	lipoprotein	1108:1118	arg1	sequence					1127:1134	a lipoprotein export sequence	1106:1134	a lipoprotein export sequence (LES)	1106:1140	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	15	67	theme	other	2188:2192	arg1	species					2204:2210	other bacterial species	2188:2210	other bacterial species	2188:2210	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	16	68	theme	amino	2343:2347	arg1	acid					2349:2352	a negatively charged rich amino acid	2317:2352	a negatively charged rich amino acid motif (LES)	2317:2364	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	8	69	theme	alpha-amylase	941:953	arg1	SusG					955:958	the alpha-amylase SusG	937:958	the alpha-amylase SusG	937:958	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	8	69	theme	alpha-amylase	941:953	arg1	enriched					970:977	enriched	970:977	enriched	970:977	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	11	70	theme	proteins	1448:1455	arg1	recruitment					1433:1443	recruitment	1433:1443	recruitment of proteins into OMVs	1433:1465	These experiments link, for the first time, surface exposure to recruitment of proteins into OMVs.
30404931	16	71	theme	motif	2354:2358	arg1	presence					2305:2312	the presence	2301:2312	the presence of a negatively charged rich amino acid motif (LES)	2301:2364	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	18	72	theme	tailor-made	2610:2620	arg1	interventions					2632:2644	tailor-made probiotic interventions	2610:2644	tailor-made probiotic interventions	2610:2644	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	18	73	from	OMVs	2752:2755	arg1	proteins					2728:2735	proteins	2728:2735	proteins of interest in OMVs	2728:2755	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	18	74	theme	LES-related	2663:2673	arg1	sequences					2675:2683	LES-related sequences	2663:2683	LES-related sequences	2663:2683	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	15	75	theme	many	2044:2047	arg1	activities					2059:2068	many enzymatic activities	2044:2068	many enzymatic activities involved in the cleavage of complex polysaccharides	2044:2120	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	10	76	theme	surface	1317:1323	arg1	exposure					1325:1332	surface exposure	1317:1332	surface exposure	1317:1332	Mutations in the LES motif caused defects in surface exposure and recruitment of SusG into OMVs.
30404931	1	77	theme	outer	185:189	arg1	membranes					191:199	the outer membranes	181:199	the outer membranes (OMs) of Gram-negative bacteria	181:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	77	theme	outer	185:189	arg1	OMs					202:204	OMs	202:204	OMs	202:204	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	11	78	attach	link	1387:1390	arg2	experiments					1375:1385	These experiments	1369:1385	These experiments	1369:1385	These experiments link, for the first time, surface exposure to recruitment of proteins into OMVs.
30404931	11	78	attach	link	1387:1390	arg1	recruitment					1433:1443	recruitment	1433:1443	recruitment of proteins into OMVs	1433:1465	These experiments link, for the first time, surface exposure to recruitment of proteins into OMVs.
30404931	18	79	from	interest	2740:2747	arg1	OMVs					2752:2755	OMVs	2752:2755	OMVs	2752:2755	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	9	80	from	face	1224:1227	arg1	translocation					1181:1193	translocation	1181:1193	translocation of SusG from the periplasmic face of the OM toward the extracellular milieu	1181:1269	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	3	81	theme	prominent	255:263	arg1	components					265:274	prominent components	255:274	prominent components of the human gut microbiota	255:302	are prominent components of the human gut microbiota, and OMVs produced by these species are proposed to play key roles in gut homeostasis.
30404931	15	82	theme	gut	2269:2271	arg1	lumen					2273:2277	the gut lumen	2265:2277	the gut lumen	2265:2277	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	5	83	theme	OMVs	528:531	arg1	composition					484:494	the protein composition	472:494	the protein composition of Bacteroides thetaiotaomicron OMVs	472:531	Here, we revisited the protein composition of Bacteroides thetaiotaomicron OMVs by mass spectrometry.
30404931	1	84	theme	Outer	112:116	arg1	vesicles					127:134	Outer membrane vesicles	112:134	Outer membrane vesicles (OMVs)	112:141	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	84	theme	Outer	112:116	arg1	structures					157:166	spherical structures	147:166	spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria	147:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	84	theme	Outer	112:116	arg1	OMVs					137:140	OMVs	137:140	OMVs	137:140	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	12	85	theme	surface-exposed	1486:1500	arg1	SusG					1502:1505	surface-exposed SusG	1486:1505	surface-exposed SusG in OMVs	1486:1513	We also show that surface-exposed SusG in OMVs is active and rescues the growth of bacterial cells incapable of growing on starch as the only carbon source.
30404931	3	86	theme	microbiota	293:302	arg1	components					265:274	prominent components	255:274	prominent components of the human gut microbiota	255:302	are prominent components of the human gut microbiota, and OMVs produced by these species are proposed to play key roles in gut homeostasis.
30404931	4	87	theme	OMV	391:393	arg1	biogenesis					395:404	OMV biogenesis	391:404	OMV biogenesis in Bacteroides	391:419	OMV biogenesis in Bacteroides is a poorly understood process.
30404931	4	87	theme	OMV	391:393	arg1	process					444:450	a poorly understood process	424:450	a poorly understood process	424:450	OMV biogenesis in Bacteroides is a poorly understood process.
30404931	18	88	theme	first	2578:2582	arg1	step					2584:2587	the first step	2574:2587	the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs	2574:2755	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	18	88	theme	first	2578:2582	arg1	This					2566:2569	This	2566:2569	This	2566:2569	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	5	89	theme	mass	536:539	arg1	spectrometry					541:552	mass spectrometry	536:552	mass spectrometry	536:552	Here, we revisited the protein composition of Bacteroides thetaiotaomicron OMVs by mass spectrometry.
30404931	15	90	theme	complex	2098:2104	arg1	polysaccharides					2106:2120	complex polysaccharides	2098:2120	complex polysaccharides	2098:2120	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	16	91	theme	alpha-amylase	2423:2435	arg1	SusG					2437:2440	the surface-exposed alpha-amylase SusG	2403:2440	the surface-exposed alpha-amylase SusG into OMVs	2403:2450	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	3	92	theme	human	283:287	arg1	microbiota					293:302	the human gut microbiota	279:302	the human gut microbiota	279:302	are prominent components of the human gut microbiota, and OMVs produced by these species are proposed to play key roles in gut homeostasis.
30404931	9	93	theme	SusG	1198:1201	arg1	translocation					1181:1193	translocation	1181:1193	translocation of SusG from the periplasmic face of the OM toward the extracellular milieu	1181:1269	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	18	94	from	proteins	2728:2735	arg1	OMVs					2752:2755	OMVs	2752:2755	OMVs	2752:2755	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	11	95	theme	surface	1413:1419	arg1	exposure					1421:1428	surface exposure	1413:1428	surface exposure	1413:1428	These experiments link, for the first time, surface exposure to recruitment of proteins into OMVs.
30404931	0	96	theme	Coupled	78:84	arg1	Processes					86:94	Coupled Processes	78:94	Coupled Processes in Bacteroides	78:109	Surface Exposure and Packing of Lipoproteins into Outer Membrane Vesicles Are Coupled Processes in Bacteroides.
30404931	5	97	theme	Bacteroides	499:509	arg1	OMVs					528:531	Bacteroides thetaiotaomicron OMVs	499:531	Bacteroides thetaiotaomicron OMVs	499:531	Here, we revisited the protein composition of Bacteroides thetaiotaomicron OMVs by mass spectrometry.
30404931	12	98	theme	incapable	1567:1575	arg1	cells					1561:1565	bacterial cells	1551:1565	bacterial cells incapable of growing on starch as the only carbon source	1551:1622	We also show that surface-exposed SusG in OMVs is active and rescues the growth of bacterial cells incapable of growing on starch as the only carbon source.
30404931	18	99	theme	interest	2740:2747	arg1	proteins					2728:2735	proteins	2728:2735	proteins of interest in OMVs	2728:2755	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	13	100	theme	other	1704:1708	arg1	organisms					1710:1718	other organisms	1704:1718	other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota	1704:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	18	101	from	step	2584:2587	arg1	generation					2596:2605	the generation	2592:2605	the generation of tailor-made probiotic interventions	2592:2644	This is the first step in the generation of tailor-made probiotic interventions that can exploit LES-related sequences to generate Bacteroides strains displaying proteins of interest in OMVs.
30404931	8	102	theme	importer	1014:1021	arg1	SusC					1023:1026	the oligosaccharide importer SusC	994:1026	the oligosaccharide importer SusC	994:1026	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	14	103	from	OMVs	1857:1860	arg1	Bacteroides					1865:1875	Bacteroides	1865:1875	Bacteroides	1865:1875	OMVs in Bacteroides have been shown to be important for the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease.
30404931	13	104	from	genus	1798:1802	arg1	Species					1769:1775	different metabolic capabilities.IMPORTANCE Species	1725:1775	different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus	1725:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	104	from	genus	1798:1802	arg1	members					1820:1826	predominant members	1808:1826	predominant members of the human gut microbiota	1808:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	12	105	theme	bacterial	1551:1559	arg1	cells					1561:1565	bacterial cells	1551:1565	bacterial cells incapable of growing on starch as the only carbon source	1551:1622	We also show that surface-exposed SusG in OMVs is active and rescues the growth of bacterial cells incapable of growing on starch as the only carbon source.
30404931	3	106	theme	key	361:363	arg1	roles					365:369	key roles	361:369	key roles	361:369	are prominent components of the human gut microbiota, and OMVs produced by these species are proposed to play key roles in gut homeostasis.
30404931	9	107	theme	extracellular	1250:1262	arg1	milieu					1264:1269	the extracellular milieu	1246:1269	the extracellular milieu	1246:1269	We found that all OMV-enriched lipoproteins possess a lipoprotein export sequence (LES), and we show that this signal mediates translocation of SusG from the periplasmic face of the OM toward the extracellular milieu.
30404931	8	108	theme	subcellular	847:857	arg1	locations					859:867	the subcellular locations	843:867	the subcellular locations of the components of the Sus system	843:903	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	14	109	theme	host-commensal	1940:1953	arg1	relationships					1955:1967	complex host-commensal relationships	1932:1967	complex host-commensal relationships	1932:1967	OMVs in Bacteroides have been shown to be important for the homeostasis of complex host-commensal relationships, mainly involving immune tolerance and protection from disease.
30404931	1	110	attach	derived	168:174	arg2	structures					157:166	spherical structures	147:166	spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria	147:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	110	attach	derived	168:174	arg1	OMs					202:204	OMs	202:204	OMs	202:204	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	110	attach	derived	168:174	arg2	vesicles					127:134	Outer membrane vesicles	112:134	Outer membrane vesicles (OMVs)	112:141	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	110	attach	derived	168:174	arg1	membranes					191:199	the outer membranes	181:199	the outer membranes (OMs) of Gram-negative bacteria	181:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	0	111	theme	Lipoproteins	32:43	arg1	Packing					21:27	Packing	21:27	Packing of Lipoproteins into Outer Membrane Vesicles	21:72	Surface Exposure and Packing of Lipoproteins into Outer Membrane Vesicles Are Coupled Processes in Bacteroides.
30404931	0	111	theme	Lipoproteins	32:43	arg1	Exposure					8:15	Surface Exposure	0:15	Surface Exposure	0:15	Surface Exposure and Packing of Lipoproteins into Outer Membrane Vesicles Are Coupled Processes in Bacteroides.
30404931	7	112	theme	utilization	782:792	arg1	PULs					800:803	PULs	800:803	PULs	800:803	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	7	112	theme	utilization	782:792	arg1	loci					794:797	polysaccharide utilization loci	767:797	polysaccharide utilization loci (PULs)	767:804	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	7	112	theme	utilization	782:792	arg1	operon					823:828	the sus operon	815:828	the sus operon	815:828	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	13	113	used	utilized	1692:1699	arg2	"					1678:1678	"public goods"	1665:1678	"public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota	1665:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	0	114	theme	Outer	50:54	arg1	Vesicles					65:72	Outer Membrane Vesicles	50:72	Outer Membrane Vesicles	50:72	Surface Exposure and Packing of Lipoproteins into Outer Membrane Vesicles Are Coupled Processes in Bacteroides.
30404931	15	115	theme	public	2148:2153	arg1	OMVs					2033:2036	OMVs	2033:2036	OMVs	2033:2036	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	15	115	theme	public	2148:2153	arg1	goods					2155:2159	public goods	2148:2159	public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen	2148:2277	OMVs carry many enzymatic activities involved in the cleavage of complex polysaccharides and have been proposed as public goods that can provide growth to other bacterial species by release of polysaccharide breakdown products into the gut lumen.
30404931	11	116	theme	first	1401:1405	arg1	time					1407:1410	the first time	1397:1410	the first time	1397:1410	These experiments link, for the first time, surface exposure to recruitment of proteins into OMVs.
30404931	8	117	theme	components	876:885	arg1	locations					859:867	the subcellular locations	843:867	the subcellular locations of the components of the Sus system	843:903	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	17	118	theme	lipoproteins	2542:2553	arg1	packing					2519:2525	packing	2519:2525	packing of Bacteroides lipoproteins into OMVs	2519:2563	Our findings strongly suggest that surface exposure is coupled to packing of Bacteroides lipoproteins into OMVs.
30404931	16	119	theme	efficient	2382:2390	arg1	packing					2392:2398	efficient packing	2382:2398	efficient packing of the surface-exposed alpha-amylase SusG into OMVs	2382:2450	This work shows that the presence of a negatively charged rich amino acid motif (LES) is required for efficient packing of the surface-exposed alpha-amylase SusG into OMVs.
30404931	13	120	dep	organisms	1710:1718	arg1	Species					1769:1775	different metabolic capabilities.IMPORTANCE Species	1725:1775	different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus	1725:1802	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	13	120	dep	organisms	1710:1718	arg1	members					1820:1826	predominant members	1808:1826	predominant members of the human gut microbiota	1808:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	10	121	theme	LES	1289:1291	arg1	motif					1293:1297	the LES motif	1285:1297	the LES motif	1285:1297	Mutations in the LES motif caused defects in surface exposure and recruitment of SusG into OMVs.
30404931	7	122	theme	OMV-enriched	726:737	arg1	lipoproteins					739:750	these OMV-enriched lipoproteins	720:750	these OMV-enriched lipoproteins	720:750	We found that most of these OMV-enriched lipoproteins are encoded by polysaccharide utilization loci (PULs), such as the sus operon.
30404931	8	123	theme	system	898:903	arg1	components					876:885	the components	872:885	the components of the Sus system	872:903	We examined the subcellular locations of the components of the Sus system and found a split localization; the alpha-amylase SusG is highly enriched in OMVs, while the oligosaccharide importer SusC remains mostly in the OM.
30404931	13	124	theme	goods	1673:1677	arg1	"					1678:1678	"public goods"	1665:1678	"public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota	1665:1854	Our results support the role of OMVs as "public goods" that can be utilized by other organisms with different metabolic capabilities.IMPORTANCE Species from the Bacteroides genus are predominant members of the human gut microbiota.
30404931	1	125	theme	bacteria	224:231	arg1	membranes					191:199	the outer membranes	181:199	the outer membranes (OMs) of Gram-negative bacteria	181:231	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30404931	1	125	theme	bacteria	224:231	arg1	OMs					202:204	OMs	202:204	OMs	202:204	Outer membrane vesicles (OMVs) are spherical structures derived from the outer membranes (OMs) of Gram-negative bacteria.
30135468	0	0	theme	tropical	77:84	arg1	forest					90:95	a tropical dry forest	75:95	a tropical dry forest	75:95	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	3	1	from	decreases	419:427	arg1	abundance					437:445	food abundance	432:445	food abundance	432:445	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	3	1	from	decreases	419:427	arg1	availability					457:468	water availability	451:468	water availability	451:468	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	8	2	dep	diversity	1383:1391	arg1	the					1379:1381	the	1379:1381	the	1379:1381	We conclude that rainfall and diet are associated with the diversity, composition, and function of the capuchin gut microbiome.
30135468	3	3	attach	linked	487:492	arg2	decreases					419:427	seasonally specific decreases	399:427	seasonally specific decreases	399:427	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	3	3	attach	linked	487:492	arg1	effects					512:518	adverse health effects	497:518	adverse health effects	497:518	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	1	4	theme	mammals	145:151	arg1	microbiota					118:127	the gut microbiota	110:127	the gut microbiota of free-ranging mammals	110:151	Research on the gut microbiota of free-ranging mammals is offering new insights into dietary ecology.
30135468	9	5	theme	microbial	1466:1474	arg1	fluctuations					1476:1487	microbial fluctuations	1466:1487	microbial fluctuations	1466:1487	Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
30135468	5	6	theme	16S	768:770	arg1	rRNA					772:775	16S rRNA	768:775	16S rRNA sequencing data	768:791	16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus.
30135468	6	7	theme	Linear	915:920	arg1	models					936:941	Linear mixed effects models	915:941	Linear mixed effects models	915:941	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	3	8	theme	seasonal	361:368	arg1	forests					383:389	seasonal tropical dry forests	361:389	seasonal tropical dry forests	361:389	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	0	9	from	Seasonality	0:10	arg1	forest					90:95	a tropical dry forest	75:95	a tropical dry forest	75:95	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	7	10	theme	shotgun	1128:1134	arg1	metagenomics					1136:1147	Whole shotgun metagenomics	1122:1147	Whole shotgun metagenomics	1122:1147	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	7	11	theme	plant	1254:1258	arg1	polysaccharides					1260:1274	plant polysaccharides	1254:1274	plant polysaccharides	1254:1274	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	3	12	theme	specific	410:417	arg1	decreases					419:427	seasonally specific decreases	399:427	seasonally specific decreases	399:427	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	0	13	theme	dry	86:88	arg1	forest					90:95	a tropical dry forest	75:95	a tropical dry forest	75:95	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	9	14	theme	populations	1563:1573	arg1	uptake					1525:1530	nutrient uptake	1516:1530	nutrient uptake	1516:1530	Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
30135468	9	14	theme	populations	1563:1573	arg1	the health					1536:1545	the health	1536:1545	the health	1536:1545	Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
30135468	9	15	theme	nutrient	1516:1523	arg1	uptake					1525:1530	nutrient uptake	1516:1530	nutrient uptake	1516:1530	Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
30135468	4	16	theme	fecal	590:594	arg1	samples					596:602	fecal samples	590:602	fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	590:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	6	17	theme	diversity	1083:1091	arg1	clusters					1093:1100	beta diversity clusters	1078:1100	beta diversity clusters by rainfall	1078:1112	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	3	18	theme	water	451:455	arg1	availability					457:468	water availability	451:468	water availability	451:468	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	4	19	from	course	536:541	arg1	2014					571:574	2014	571:574	2014	571:574	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	7	20	theme	Whole	1122:1126	arg1	metagenomics					1136:1147	Whole shotgun metagenomics	1122:1147	Whole shotgun metagenomics	1122:1147	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	6	21	dep	associated	988:997	arg1	whereas					1070:1076	whereas	1070:1076	whereas	1070:1076	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	1	22	theme	new	165:167	arg1	insights					169:176	new insights	165:176	new insights into dietary ecology	165:197	Research on the gut microbiota of free-ranging mammals is offering new insights into dietary ecology.
30135468	7	23	theme	carbohydrate-binding	1196:1215	arg1	modules					1217:1223	carbohydrate-binding modules	1196:1223	carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin	1196:1285	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	0	24	from	microbiota	23:32	arg1	forest					90:95	a tropical dry forest	75:95	a tropical dry forest	75:95	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	7	25	theme	polysaccharides	1260:1274	arg1	digestion					1241:1249	digestion	1241:1249	digestion of plant polysaccharides	1241:1274	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	7	25	theme	polysaccharides	1260:1274	arg1	chitin					1280:1285	chitin	1280:1285	chitin	1280:1285	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	2	26	theme	ecological	306:315	arg1	variation					317:325	ecological variation	306:325	ecological variation through time	306:338	However, for free-ranging primates, little information is available for how microbiomes are influenced by ecological variation through time.
30135468	4	27	theme	capucinus	681:689	arg1	imitator					691:698	Cebus capucinus imitator	675:698	Cebus capucinus imitator	675:698	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	27	theme	capucinus	681:689	arg1	monkeys					666:672	free-ranging white-faced capuchin monkeys	632:672	free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	632:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	28	from	2014	571:574	arg1	course					536:541	the course	532:541	the course of a seasonal transition in 2014	532:574	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	0	29	theme	gut	19:21	arg1	microbiota					23:32	the gut microbiota	15:32	the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest	15:95	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	5	30	theme	monkey	853:858	arg1	gut					860:862	the white-faced capuchin monkey gut	828:862	the white-faced capuchin monkey gut	828:862	16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus.
30135468	4	31	theme	Cebus	675:679	arg1	imitator					691:698	Cebus capucinus imitator	675:698	Cebus capucinus imitator	675:698	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	31	theme	Cebus	675:679	arg1	monkeys					666:672	free-ranging white-faced capuchin monkeys	632:672	free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	632:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	3	32	theme	dry	379:381	arg1	forests					383:389	seasonal tropical dry forests	361:389	seasonal tropical dry forests	361:389	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	4	33	theme	transition	557:566	arg1	course					536:541	the course	532:541	the course of a seasonal transition in 2014	532:574	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	9	34	dep	likely	1493:1498	arg1	contributing					1500:1511	contributing	1500:1511	contributing to nutrient uptake and the health of wild primate populations	1500:1573	Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
30135468	6	35	theme	arthropods	1058:1067	arg1	consumption					1033:1043	consumption	1033:1043	consumption of fruit and arthropods	1033:1067	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	6	35	theme	arthropods	1058:1067	arg1	availability					1016:1027	availability	1016:1027	availability	1016:1027	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	8	36	theme	gut	1436:1438	arg1	microbiome					1440:1449	the capuchin gut microbiome	1423:1449	the capuchin gut microbiome	1423:1449	We conclude that rainfall and diet are associated with the diversity, composition, and function of the capuchin gut microbiome.
30135468	1	37	theme	dietary	183:189	arg1	ecology					191:197	dietary ecology	183:197	dietary ecology	183:197	Research on the gut microbiota of free-ranging mammals is offering new insights into dietary ecology.
30135468	4	38	from	transition	557:566	arg1	2014					571:574	2014	571:574	2014	571:574	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	6	39	theme	mixed	922:926	arg1	models					936:941	Linear mixed effects models	915:941	Linear mixed effects models	915:941	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	5	40	theme	other	812:816	arg1	primates					818:825	other primates	812:825	other primates	812:825	16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus.
30135468	5	41	theme	rRNA	772:775	arg1	data					788:791	16S rRNA sequencing data	768:791	16S rRNA sequencing data	768:791	16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus.
30135468	9	42	theme	wild	1550:1553	arg1	populations					1563:1573	wild primate populations	1550:1573	wild primate populations	1550:1573	Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
30135468	5	43	theme	white-faced	832:842	arg1	gut					860:862	the white-faced capuchin monkey gut	828:862	the white-faced capuchin monkey gut	828:862	16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus.
30135468	6	44	dep	season	1114:1119	arg1	clusters					1093:1100	beta diversity clusters	1078:1100	beta diversity clusters by rainfall	1078:1112	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	6	45	theme	beta	1078:1081	arg1	clusters					1093:1100	beta diversity clusters	1078:1100	beta diversity clusters by rainfall	1078:1112	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	4	46	theme	capuchin	657:664	arg1	imitator					691:698	Cebus capucinus imitator	675:698	Cebus capucinus imitator	675:698	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	46	theme	capuchin	657:664	arg1	monkeys					666:672	free-ranging white-faced capuchin monkeys	632:672	free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	632:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	0	47	theme	microbiota	23:32	arg1	Seasonality					0:10	Seasonality	0:10	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.	0:96	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	3	48	theme	food	432:435	arg1	abundance					437:445	food abundance	432:445	food abundance	432:445	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	2	49	theme	free-ranging	213:224	arg1	primates					226:233	free-ranging primates	213:233	free-ranging primates	213:233	However, for free-ranging primates, little information is available for how microbiomes are influenced by ecological variation through time.
30135468	4	50	theme	white-faced	645:655	arg1	imitator					691:698	Cebus capucinus imitator	675:698	Cebus capucinus imitator	675:698	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	50	theme	white-faced	645:655	arg1	monkeys					666:672	free-ranging white-faced capuchin monkeys	632:672	free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	632:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	0	51	theme	white-faced	50:60	arg1	capuchins					62:70	free-ranging white-faced capuchins	37:70	free-ranging white-faced capuchins	37:70	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	6	52	theme	genera	977:982	arg1	abundances					957:966	abundances	957:966	abundances of these genera	957:982	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	3	53	theme	adverse	497:503	arg1	effects					512:518	adverse health effects	497:518	adverse health effects	497:518	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	0	54	theme	free-ranging	37:48	arg1	capuchins					62:70	free-ranging white-faced capuchins	37:70	free-ranging white-faced capuchins	37:70	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	4	55	theme	seasonal	548:555	arg1	transition					557:566	a seasonal transition	546:566	a seasonal transition in 2014	546:574	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	8	56	theme	microbiome	1440:1449	arg1	composition					1394:1404	composition	1394:1404	composition	1394:1404	We conclude that rainfall and diet are associated with the diversity, composition, and function of the capuchin gut microbiome.
30135468	8	56	theme	microbiome	1440:1449	arg1	function					1411:1418	function	1411:1418	function	1411:1418	We conclude that rainfall and diet are associated with the diversity, composition, and function of the capuchin gut microbiome.
30135468	8	56	theme	microbiome	1440:1449	arg1	diversity					1383:1391	diversity	1383:1391	diversity	1383:1391	We conclude that rainfall and diet are associated with the diversity, composition, and function of the capuchin gut microbiome.
30135468	3	57	theme	health	505:510	arg1	effects					512:518	adverse health effects	497:518	adverse health effects	497:518	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
30135468	7	58	theme	capuchin	1167:1174	arg1	gut					1176:1178	the capuchin gut	1163:1178	the capuchin gut	1163:1178	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	5	59	theme	sequencing	777:786	arg1	data					788:791	16S rRNA sequencing data	768:791	16S rRNA sequencing data	768:791	16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus.
30135468	8	60	theme	capuchin	1427:1434	arg1	microbiome					1440:1449	the capuchin gut microbiome	1423:1449	the capuchin gut microbiome	1423:1449	We conclude that rainfall and diet are associated with the diversity, composition, and function of the capuchin gut microbiome.
30135468	1	61	theme	gut	114:116	arg1	microbiota					118:127	the gut microbiota	110:127	the gut microbiota of free-ranging mammals	110:151	Research on the gut microbiota of free-ranging mammals is offering new insights into dietary ecology.
30135468	1	62	from	Research	98:105	arg1	microbiota					118:127	the gut microbiota	110:127	the gut microbiota of free-ranging mammals	110:151	Research on the gut microbiota of free-ranging mammals is offering new insights into dietary ecology.
30135468	6	63	theme	fruit	1048:1052	arg1	consumption					1033:1043	consumption	1033:1043	consumption of fruit and arthropods	1033:1067	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	6	63	theme	fruit	1048:1052	arg1	availability					1016:1027	availability	1016:1027	availability	1016:1027	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	0	64	from	forest	90:95	arg1	Seasonality					0:10	Seasonality	0:10	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.	0:96	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	7	65	theme	dietary	1306:1312	arg1	patterns					1314:1321	seasonal dietary patterns	1297:1321	seasonal dietary patterns	1297:1321	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	9	66	theme	primate	1555:1561	arg1	populations					1563:1573	wild primate populations	1550:1573	wild primate populations	1550:1573	Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
30135468	4	67	from	groups	622:627	arg1	samples					596:602	fecal samples	590:602	fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	590:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	5	68	theme	capuchin	844:851	arg1	gut					860:862	the white-faced capuchin monkey gut	828:862	the white-faced capuchin monkey gut	828:862	16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus.
30135468	2	69	theme	little	236:241	arg1	information					243:253	little information	236:253	little information	236:253	However, for free-ranging primates, little information is available for how microbiomes are influenced by ecological variation through time.
30135468	4	70	theme	free-ranging	632:643	arg1	imitator					691:698	Cebus capucinus imitator	675:698	Cebus capucinus imitator	675:698	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	70	theme	free-ranging	632:643	arg1	monkeys					666:672	free-ranging white-faced capuchin monkeys	632:672	free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	632:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	7	71	theme	seasonal	1297:1304	arg1	patterns					1314:1321	seasonal dietary patterns	1297:1321	seasonal dietary patterns	1297:1321	Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns.
30135468	4	72	theme	monkeys	666:672	arg1	imitator					691:698	Cebus capucinus imitator	675:698	Cebus capucinus imitator	675:698	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	72	theme	monkeys	666:672	arg1	monkeys					666:672	free-ranging white-faced capuchin monkeys	632:672	free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	632:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	72	theme	monkeys	666:672	arg1	groups					622:627	three social groups	609:627	three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	609:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	0	73	theme	capuchins	62:70	arg1	microbiota					23:32	the gut microbiota	15:32	the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest	15:95	Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest.
30135468	6	74	theme	effects	928:934	arg1	models					936:941	Linear mixed effects models	915:941	Linear mixed effects models	915:941	Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season.
30135468	4	75	theme	social	615:620	arg1	imitator					691:698	Cebus capucinus imitator	675:698	Cebus capucinus imitator	675:698	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	75	theme	social	615:620	arg1	monkeys					666:672	free-ranging white-faced capuchin monkeys	632:672	free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	632:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	4	75	theme	social	615:620	arg1	groups					622:627	three social groups	609:627	three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator)	609:699	Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica.
30135468	1	76	theme	free-ranging	132:143	arg1	mammals					145:151	free-ranging mammals	132:151	free-ranging mammals	132:151	Research on the gut microbiota of free-ranging mammals is offering new insights into dietary ecology.
30135468	3	77	theme	tropical	370:377	arg1	forests					383:389	seasonal tropical dry forests	361:389	seasonal tropical dry forests	361:389	Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects.
31019496	6	0	theme	extracted	952:960	arg1	components					969:978	the extracted matrix components	948:978	the extracted matrix components	948:978	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	2	1	theme	options	347:353	arg1	due					397:399	due	397:399	due	397:399	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	2	1	theme	options	347:353	arg1	limitations					316:326	The limitations	312:326	The limitations of the therapeutic options against Klebsiella pneumoniae	312:383	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	1	2	theme	capable	252:258	arg1	pathogen					242:249	a human pathogen	234:249	a human pathogen	234:249	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	1	2	theme	capable	252:258	arg1	pneumoniae					220:229	Klebsiella pneumoniae	209:229	Klebsiella pneumoniae	209:229	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	6	3	theme	MALDI	1235:1239	arg1	analysis					1247:1254	MALDI MS/MS analysis	1235:1254	MALDI MS/MS analysis	1235:1254	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	3	4	theme	Klebsiella	565:574	arg1	isolates					587:594	Klebsiella pneumoniae isolates	565:594	Klebsiella pneumoniae isolates	565:594	We utilized a newer approach for classification of biofilm producing Klebsiella pneumoniae isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm.
31019496	15	5	theme	biofilm	2334:2340	arg1	matrix					2342:2347	the biofilm matrix	2330:2347	the biofilm matrix	2330:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	11	6	theme	proteins	1687:1694	arg1	presence					1665:1672	the presence	1661:1672	the presence of different proteins within the biofilm	1661:1713	MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm.
31019496	3	7	theme	biofilm	547:553	arg1	classification					529:542	classification	529:542	classification of biofilm	529:553	We utilized a newer approach for classification of biofilm producing Klebsiella pneumoniae isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm.
31019496	3	8	dep	evaluated	616:624	arg1	biofilm					674:680	its biofilm	670:680	its biofilm	670:680	We utilized a newer approach for classification of biofilm producing Klebsiella pneumoniae isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm.
31019496	14	9	theme	related	1949:1955	arg1	proteins					1940:1947	proteins	1940:1947	proteins related to energy and metabolism	1940:1980	Similarly, proteins related to energy and metabolism were 8 and those related to capsule and cell wall synthesis were 4.
31019496	0	10	dep	in	76:77	arg1	vitro					79:83	vitro	79:83	vitro	79:83	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	6	11	theme	gel-based	1146:1154	arg1	SDS-PAGE					1173:1180	SDS-PAGE	1173:1180	SDS-PAGE	1173:1180	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	11	theme	gel-based	1146:1154	arg1	electrophoresis					1156:1170	one-dimensional gel-based electrophoresis	1130:1170	one-dimensional gel-based electrophoresis (SDS-PAGE)	1130:1181	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	12	theme	sophisticated	998:1010	arg1	analysis					1012:1019	sophisticated analysis	998:1019	sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy	998:1080	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	15	13	theme	slime	2281:2285	arg1	portions					2265:2272	weakening/targeting certain portions	2237:2272	weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix	2237:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	5	14	theme	confocal	893:900	arg1	CLSM					929:932	CLSM	929:932	CLSM	929:932	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	5	14	theme	confocal	893:900	arg1	microscopy					917:926	confocal laser scanning microscopy	893:926	confocal laser scanning microscopy (CLSM)	893:933	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	0	15	theme	Matrix	145:150	arg1	Chemistry					152:160	the Biofilm Matrix Chemistry	133:160	the Biofilm Matrix Chemistry	133:160	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	9	16	theme	unique	1531:1536	arg1	bands					1546:1550	various common and unique protein bands	1512:1550	various common and unique protein bands	1512:1550	The proteins were harvested and subjected to SDS-PAGE which revealed various common and unique protein bands.
31019496	3	17	dep	Klebsiella	565:574	arg1	pneumoniae					576:585	pneumoniae	576:585	pneumoniae	576:585	We utilized a newer approach for classification of biofilm producing Klebsiella pneumoniae isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm.
31019496	5	18	theme	spatial	798:804	arg1	distribution					806:817	The spatial distribution	794:817	The spatial distribution of sugars and proteins	794:840	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	15	19	theme	certain	2257:2263	arg1	portions					2265:2272	weakening/targeting certain portions	2237:2272	weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix	2237:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	15	20	theme	common	2305:2310	arg1	block					2321:2325	the most common building block	2296:2325	the most common building block of the biofilm matrix	2296:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	15	20	theme	common	2305:2310	arg1	slime					2281:2285	the slime	2277:2285	the slime which is the most common building block of the biofilm matrix	2277:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	0	21	theme	in	76:77	arg1	Biofilm					85:91	Their in vitro Biofilm	70:91	Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content	70:206	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	12	22	theme	different	1723:1731	arg1	proteins					1733:1740	The 55 different proteins	1716:1740	The 55 different proteins	1716:1740	The 55 different proteins were identified including both cytosolic and membrane proteins.
31019496	15	23	theme	biofilm	2109:2115	arg1	composition					2117:2127	Klebsiella biofilm composition	2098:2127	Klebsiella biofilm composition	2098:2127	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	2	24	theme	harboring	448:456	arg1	determinants					458:469	biofilm and harboring determinants	436:469	determinants	458:469	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	4	25	theme	bacterial	774:782	arg1	biofilms					784:791	representative bacterial biofilms	759:791	representative bacterial biofilms	759:791	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	14	26	theme	wall	2027:2030	arg1	synthesis					2032:2040	cell wall synthesis	2022:2040	cell wall synthesis	2022:2040	Similarly, proteins related to energy and metabolism were 8 and those related to capsule and cell wall synthesis were 4.
31019496	2	27	theme	biofilm	436:442	arg1	determinants					458:469	biofilm and harboring determinants	436:469	determinants	458:469	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	0	28	theme	Clinical	18:25	arg1	Isolates					27:34	Clinical Isolates	18:34	Clinical Isolates	18:34	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	1	29	theme	abiotic	283:289	arg1	surfaces					302:309	abiotic and biotic surfaces	283:309	abiotic and biotic surfaces	283:309	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	2	30	theme	resistance	484:493	arg1	determinants					458:469	biofilm and harboring determinants	436:469	determinants	458:469	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	2	31	theme	innate	408:413	arg1	capabilities					415:426	its innate capabilities	404:426	its innate capabilities	404:426	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	1	32	theme	biotic	295:300	arg1	surfaces					302:309	abiotic and biotic surfaces	283:309	abiotic and biotic surfaces	283:309	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	15	33	theme	better	2161:2166	arg1	strategies					2168:2177	better strategies	2161:2177	better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix	2161:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	7	34	theme	total	1332:1336	arg1	proteins					1298:1305	its total proteins	1288:1305	its total proteins	1288:1305	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	7	34	theme	total	1332:1336	arg1	content					1345:1351	total acetyl content	1332:1351	total acetyl content	1332:1351	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	2	35	theme	therapeutic	335:345	arg1	options					347:353	the therapeutic options	331:353	the therapeutic options	331:353	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	0	36	theme	pneumoniae	50:59	arg1	Classification					0:13	Classification	0:13	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.	0:207	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	6	37	theme	high	1184:1187	arg1	HPLC					1224:1227	HPLC	1224:1227	HPLC	1224:1227	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	37	theme	high	1184:1187	arg1	chromatography					1208:1221	high performance liquid chromatography	1184:1221	high performance liquid chromatography (HPLC)	1184:1228	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	13	38	theme	protein	1840:1846	arg1	synthesis					1848:1856	protein synthesis	1840:1856	protein synthesis	1840:1856	About 22 proteins were related to protein synthesis and processing while 15 proteins were identified related to virulence.
31019496	6	39	theme	magnetic	1091:1098	arg1	NMR					1111:1113	NMR	1111:1113	NMR	1111:1113	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	39	theme	magnetic	1091:1098	arg1	resonance					1100:1108	nuclear magnetic resonance	1083:1108	nuclear magnetic resonance (NMR) spectroscopy	1083:1127	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	5	40	theme	scanning	908:915	arg1	CLSM					929:932	CLSM	929:932	CLSM	929:932	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	5	40	theme	scanning	908:915	arg1	microscopy					917:926	confocal laser scanning microscopy	893:926	confocal laser scanning microscopy (CLSM)	893:933	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	1	41	theme	human	236:240	arg1	pathogen					242:249	a human pathogen	234:249	a human pathogen	234:249	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	1	41	theme	human	236:240	arg1	pneumoniae					220:229	Klebsiella pneumoniae	209:229	Klebsiella pneumoniae	209:229	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	6	42	theme	matrix	962:967	arg1	components					969:978	the extracted matrix components	948:978	the extracted matrix components	948:978	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	11	43	theme	different	1677:1685	arg1	proteins					1687:1694	different proteins	1677:1694	different proteins	1677:1694	MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm.
31019496	11	44	theme	protein	1638:1644	arg1	band					1646:1649	this common protein band	1626:1649	this common protein band	1626:1649	MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm.
31019496	3	45	theme	newer	510:514	arg1	approach					516:523	a newer approach	508:523	a newer approach for classification of biofilm	508:553	We utilized a newer approach for classification of biofilm producing Klebsiella pneumoniae isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm.
31019496	15	46	theme	matrix	2342:2347	arg1	block					2321:2325	the most common building block	2296:2325	the most common building block of the biofilm matrix	2296:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	15	46	theme	matrix	2342:2347	arg1	slime					2281:2285	the slime	2277:2285	the slime which is the most common building block of the biofilm matrix	2277:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	7	47	theme	total	1292:1296	arg1	proteins					1298:1305	its total proteins	1288:1305	its total proteins	1288:1305	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	7	47	theme	total	1292:1296	arg1	sugars					1314:1319	total sugars	1308:1319	total sugars	1308:1319	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	7	47	theme	total	1292:1296	arg1	content					1345:1351	total acetyl content	1332:1351	total acetyl content	1332:1351	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	7	47	theme	total	1292:1296	arg1	uronates					1322:1329	uronates	1322:1329	uronates	1322:1329	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	0	48	theme	Protein	192:198	arg1	Content					200:206	the Protein Content	188:206	the Protein Content	188:206	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	5	49	theme	laser	902:906	arg1	CLSM					929:932	CLSM	929:932	CLSM	929:932	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	5	49	theme	laser	902:906	arg1	microscopy					917:926	confocal laser scanning microscopy	893:926	confocal laser scanning microscopy (CLSM)	893:933	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	11	50	theme	MALDI	1603:1607	arg1	results					1615:1621	MALDI MS/MS results	1603:1621	MALDI MS/MS results of this common protein band	1603:1649	MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm.
31019496	12	51	theme	membrane	1787:1794	arg1	proteins					1796:1803	membrane proteins	1787:1803	membrane proteins	1787:1803	The 55 different proteins were identified including both cytosolic and membrane proteins.
31019496	3	52	used	utilized	499:506	arg2	We					496:497	We	496:497	We	496:497	We utilized a newer approach for classification of biofilm producing Klebsiella pneumoniae isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm.
31019496	5	53	theme	biofilm	872:878	arg1	matrix					880:885	the biofilm matrix	868:885	the biofilm matrix	868:885	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	6	54	theme	liquid	1201:1206	arg1	HPLC					1224:1227	HPLC	1224:1227	HPLC	1224:1227	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	54	theme	liquid	1201:1206	arg1	chromatography					1208:1221	high performance liquid chromatography	1184:1221	high performance liquid chromatography (HPLC)	1184:1228	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	0	55	theme	Biofilm	137:143	arg1	Chemistry					152:160	the Biofilm Matrix Chemistry	133:160	the Biofilm Matrix Chemistry	133:160	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	1	56	theme	Klebsiella	209:218	arg1	pathogen					242:249	a human pathogen	234:249	a human pathogen	234:249	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	1	56	theme	Klebsiella	209:218	arg1	pneumoniae					220:229	Klebsiella pneumoniae	209:229	Klebsiella pneumoniae	209:229	Klebsiella pneumoniae is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces.
31019496	0	57	theme	Chemistry	152:160	arg1	Elucidation					118:128	Elucidation	118:128	Elucidation of the Biofilm Matrix Chemistry	118:160	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	0	57	theme	Chemistry	152:160	arg1	Capabilities					101:112	Capabilities	101:112	Capabilities	101:112	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	4	58	theme	polysaccharides	725:739	arg1	amount					715:720	the amount	711:720	the amount of polysaccharides and proteins	711:752	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	4	58	theme	polysaccharides	725:739	arg1	proteins					745:752	proteins	745:752	proteins	745:752	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	4	58	theme	polysaccharides	725:739	arg1	polysaccharides					725:739	polysaccharides	725:739	polysaccharides	725:739	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	0	59	theme	Special	167:173	arg1	Reference					175:183	Special Reference	167:183	Special Reference to the Protein Content	167:206	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	3	60	theme	slime	647:651	arg1	chemistry					630:638	the chemistry	626:638	the chemistry of its slime	626:651	We utilized a newer approach for classification of biofilm producing Klebsiella pneumoniae isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm.
31019496	9	61	theme	protein	1538:1544	arg1	bands					1546:1550	various common and unique protein bands	1512:1550	various common and unique protein bands	1512:1550	The proteins were harvested and subjected to SDS-PAGE which revealed various common and unique protein bands.
31019496	6	62	theme	nuclear	1083:1089	arg1	NMR					1111:1113	NMR	1111:1113	NMR	1111:1113	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	62	theme	nuclear	1083:1089	arg1	resonance					1100:1108	nuclear magnetic resonance	1083:1108	nuclear magnetic resonance (NMR) spectroscopy	1083:1127	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	63	dep	Fourier	1035:1041	arg1	transform					1043:1051	transform	1043:1051	transform infrared (FTIR) spectroscopy	1043:1080	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	4	64	theme	proteins	745:752	arg1	amount					715:720	the amount	711:720	the amount of polysaccharides and proteins	711:752	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	4	64	theme	proteins	745:752	arg1	proteins					745:752	proteins	745:752	proteins	745:752	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	4	64	theme	proteins	745:752	arg1	polysaccharides					725:739	polysaccharides	725:739	polysaccharides	725:739	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	7	65	theme	total	1308:1312	arg1	proteins					1298:1305	its total proteins	1288:1305	its total proteins	1288:1305	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	7	65	theme	total	1308:1312	arg1	sugars					1314:1319	total sugars	1308:1319	total sugars	1308:1319	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	15	66	theme	weakening/targeting	2237:2255	arg1	portions					2265:2272	weakening/targeting certain portions	2237:2272	weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix	2237:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	6	67	dep	infrared	1053:1060	arg1	FTIR					1063:1066	FTIR	1063:1066	FTIR	1063:1066	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	68	theme	MS/MS	1241:1245	arg1	analysis					1247:1254	MALDI MS/MS analysis	1235:1254	MALDI MS/MS analysis	1235:1254	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	15	69	theme	Klebsiella	2098:2107	arg1	composition					2117:2127	Klebsiella biofilm composition	2098:2127	Klebsiella biofilm composition	2098:2127	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	6	70	theme	infrared	1053:1060	arg1	spectroscopy					1069:1080	infrared (FTIR) spectroscopy	1053:1080	infrared (FTIR) spectroscopy	1053:1080	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	71	theme	one-dimensional	1130:1144	arg1	SDS-PAGE					1173:1180	SDS-PAGE	1173:1180	SDS-PAGE	1173:1180	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	71	theme	one-dimensional	1130:1144	arg1	electrophoresis					1156:1170	one-dimensional gel-based electrophoresis	1130:1170	one-dimensional gel-based electrophoresis (SDS-PAGE)	1130:1181	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	4	72	theme	representative	759:772	arg1	biofilms					784:791	representative bacterial biofilms	759:791	representative bacterial biofilms	759:791	We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms.
31019496	0	73	theme	Isolates	27:34	arg1	Classification					0:13	Classification	0:13	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.	0:207	Classification of Clinical Isolates of Klebsiella pneumoniae Based on Their in vitro Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
31019496	14	74	theme	cell	2022:2025	arg1	synthesis					2032:2040	cell wall synthesis	2022:2040	cell wall synthesis	2022:2040	Similarly, proteins related to energy and metabolism were 8 and those related to capsule and cell wall synthesis were 4.
31019496	7	75	theme	acetyl	1338:1343	arg1	proteins					1298:1305	its total proteins	1288:1305	its total proteins	1288:1305	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	7	75	theme	acetyl	1338:1343	arg1	content					1345:1351	total acetyl content	1332:1351	total acetyl content	1332:1351	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	8	76	theme	only/major	1403:1412	arg1	constituent					1414:1424	the only/major constituent	1399:1424	the only/major constituent of its biofilms	1399:1440	Results suggest sugars are not the only/major constituent of its biofilms.
31019496	5	77	theme	sugars	822:827	arg1	distribution					806:817	The spatial distribution	794:817	The spatial distribution of sugars and proteins	794:840	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	15	78	theme	building	2312:2319	arg1	block					2321:2325	the most common building block	2296:2325	the most common building block of the biofilm matrix	2296:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	15	78	theme	building	2312:2319	arg1	slime					2281:2285	the slime	2277:2285	the slime which is the most common building block of the biofilm matrix	2277:2347	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	9	79	theme	various	1512:1518	arg1	bands					1546:1550	various common and unique protein bands	1512:1550	various common and unique protein bands	1512:1550	The proteins were harvested and subjected to SDS-PAGE which revealed various common and unique protein bands.
31019496	6	80	theme	resonance	1100:1108	arg1	spectroscopy					1116:1127	nuclear magnetic resonance (NMR) spectroscopy	1083:1127	nuclear magnetic resonance (NMR) spectroscopy	1083:1127	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	2	81	theme	multidrug	474:482	arg1	resistance					484:493	multidrug resistance	474:493	multidrug resistance	474:493	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
31019496	5	82	theme	proteins	833:840	arg1	distribution					806:817	The spatial distribution	794:817	The spatial distribution of sugars and proteins	794:840	The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM).
31019496	6	83	theme	performance	1189:1199	arg1	HPLC					1224:1227	HPLC	1224:1227	HPLC	1224:1227	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	6	83	theme	performance	1189:1199	arg1	chromatography					1208:1221	high performance liquid chromatography	1184:1221	high performance liquid chromatography (HPLC)	1184:1228	Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis.
31019496	10	84	theme	common	1557:1562	arg1	band					1564:1567	The common band	1553:1567	The common band	1553:1567	The common band was excised and analyzed by HPLC.
31019496	8	85	theme	biofilms	1433:1440	arg1	constituent					1414:1424	the only/major constituent	1399:1424	the only/major constituent of its biofilms	1399:1440	Results suggest sugars are not the only/major constituent of its biofilms.
31019496	11	86	theme	MS/MS	1609:1613	arg1	results					1615:1621	MALDI MS/MS results	1603:1621	MALDI MS/MS results of this common protein band	1603:1649	MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm.
31019496	8	87	dep	suggest	1376:1382	arg1	constituent					1414:1424	the only/major constituent	1399:1424	the only/major constituent of its biofilms	1399:1440	Results suggest sugars are not the only/major constituent of its biofilms.
31019496	11	88	theme	band	1646:1649	arg1	results					1615:1621	MALDI MS/MS results	1603:1621	MALDI MS/MS results of this common protein band	1603:1649	MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm.
31019496	9	89	theme	common	1520:1525	arg1	bands					1546:1550	various common and unique protein bands	1512:1550	various common and unique protein bands	1512:1550	The proteins were harvested and subjected to SDS-PAGE which revealed various common and unique protein bands.
31019496	15	90	theme	composition	2117:2127	arg1	understanding					2081:2093	our understanding	2077:2093	our understanding of Klebsiella biofilm composition	2077:2127	These results will improve our understanding of Klebsiella biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
31019496	7	91	theme	proteins	1298:1305	arg1	quantification					1270:1283	the quantification	1266:1283	the quantification of its total proteins, total sugars, uronates, total acetyl content	1266:1351	Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done.
31019496	11	92	theme	common	1631:1636	arg1	band					1646:1649	this common protein band	1626:1649	this common protein band	1626:1649	MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm.
31019496	2	93	theme	Klebsiella	363:372	arg1	pneumoniae					374:383	Klebsiella pneumoniae	363:383	Klebsiella pneumoniae	363:383	The limitations of the therapeutic options against Klebsiella pneumoniae is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance.
30453909	13	0	theme	cancer	1868:1873	arg1	cells					1875:1879	bladder cancer cells	1860:1879	bladder cancer cells	1860:1879	Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum.
30453909	1	1	link	hyper-O-linked	142:155	arg1	N-acetylglucosaminylation					157:181	hyper-O-linked N-acetylglucosaminylation	142:181	hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation)	142:199	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	1	1	link	hyper-O-linked	142:155	arg1	O-GlcNAcylation					184:198	O-GlcNAcylation	184:198	O-GlcNAcylation	184:198	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	9	2	located	observed	1293:1300	arg1	cytoplasm					1317:1325	cytoplasm	1317:1325	cytoplasm	1317:1325	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	2	located	observed	1293:1300	arg1	nucleus					1305:1311	nucleus	1305:1311	nucleus	1305:1311	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	2	located	observed	1293:1300	arg2	OGT					1284:1286	OGT	1284:1286	OGT	1284:1286	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	2	located	observed	1293:1300	arg2	O-GlcNAcylation					1264:1278	O-GlcNAcylation	1264:1278	O-GlcNAcylation	1264:1278	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	11	3	theme	bladder	1677:1683	arg1	cells					1692:1696	bladder cancer cells	1677:1696	bladder cancer cells	1677:1696	It also increased autophagy in bladder cancer cells.
30453909	7	4	theme	OGT	1136:1138	arg1	knockdown					1140:1148	OGT knockdown	1136:1148	OGT knockdown	1136:1148	MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown.
30453909	3	5	theme	cell	572:575	arg1	lines					577:581	cell lines	572:581	cell lines	572:581	The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis.
30453909	1	6	theme	bladder	298:304	arg1	cancer					306:311	human bladder cancer	292:311	human bladder cancer	292:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	6	7	theme	cells	927:931	arg1	autophagy					899:907	The autophagy	895:907	The autophagy of bladder cancer cells	895:931	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	5	8	theme	cycle	844:848	arg1	analysis					850:857	cell cycle analysis	839:857	cell cycle analysis	839:857	Cell apoptosis and cell cycle analysis were detected using flow cytometry.
30453909	10	9	theme	tumor	1566:1570	arg1	growth					1572:1577	xenograft tumor growth	1556:1577	xenograft tumor growth	1556:1577	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	4	10	theme	cancer	698:703	arg1	proliferation					673:685	the cell proliferation	664:685	the cell proliferation of bladder cancer	664:703	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	13	11	theme	Reducing	1776:1783	arg1	hyper-O-GlcNAcylation					1785:1805	Reducing hyper-O-GlcNAcylation	1776:1805	Reducing hyper-O-GlcNAcylation by OGT knockdown	1776:1822	Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum.
30453909	7	12	theme	cells	1111:1115	arg1	sensitivity					1081:1091	the sensitivity	1077:1091	the sensitivity of bladder cancer cells to cisplatin	1077:1128	MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown.
30453909	8	13	theme	bladder	1225:1231	arg1	tissues					1240:1246	bladder cancer tissues	1225:1246	bladder cancer tissues	1225:1246	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	7	14	theme	bladder	1096:1102	arg1	cells					1111:1115	bladder cancer cells	1096:1115	bladder cancer cells	1096:1115	MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown.
30453909	6	15	theme	GFP-LC3	987:993	arg1	plasmid					995:1001	GFP-LC3 plasmid	987:1001	GFP-LC3 plasmid	987:1001	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	4	16	theme	cell	668:671	arg1	proliferation					673:685	the cell proliferation	664:685	the cell proliferation of bladder cancer	664:703	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	10	17	theme	cycle	1632:1636	arg1	arrest					1638:1643	cell cycle arrest	1627:1643	cell cycle arrest	1627:1643	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	7	18	theme	MTT	1043:1045	arg1	assay					1047:1051	MTT assay	1043:1051	MTT assay	1043:1051	MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown.
30453909	8	19	theme	cell	1252:1255	arg1	lines					1257:1261	cell lines	1252:1261	cell lines	1252:1261	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	3	20	theme	Western	607:613	arg1	analysis					620:627	the Western blot analysis	603:627	the Western blot analysis	603:627	The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis.
30453909	12	21	theme	increased	1723:1731	arg1	autophagy					1733:1741	increased autophagy	1723:1741	increased autophagy pro-survival, but not pro-death	1723:1773	This study demonstrated increased autophagy pro-survival, but not pro-death.
30453909	6	22	theme	blot	968:971	arg1	analysis					973:980	the Western blot analysis	956:980	the Western blot analysis	956:980	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	4	23	theme	-2,5-diphenyltetrazolium	753:776	arg1	MTT					787:789	MTT	787:789	MTT	787:789	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	4	23	theme	-2,5-diphenyltetrazolium	753:776	arg1	bromide					778:784	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide	725:784	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)	725:790	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	6	24	used	used	1007:1010	arg2	plasmid					995:1001	GFP-LC3 plasmid	987:1001	GFP-LC3 plasmid	987:1001	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	12	25	theme	pro-survival	1743:1754	arg1	autophagy					1733:1741	increased autophagy	1723:1741	increased autophagy pro-survival, but not pro-death	1723:1773	This study demonstrated increased autophagy pro-survival, but not pro-death.
30453909	1	26	dep	BACKGROUND	103:112	arg1	aimed					125:129	aimed	125:129	aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer	125:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	4	27	from	effects	634:640	arg1	proliferation					673:685	the cell proliferation	664:685	the cell proliferation of bladder cancer	664:703	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	14	28	from	response	2017:2024	arg1	cancer					2037:2042	bladder cancer	2029:2042	bladder cancer	2029:2042	CONCLUSIONS The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.
30453909	10	29	theme	OGT	1477:1479	arg1	knockdown					1481:1489	OGT knockdown	1477:1489	OGT knockdown	1477:1489	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	2	30	dep	cancer	484:489	arg1	N = 169					511:517	N = 169	511:517	N = 169	511:517	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	2	30	dep	cancer	484:489	arg1	microarrays					498:508	tissue microarrays	491:508	human bladder cancer tissue microarrays (N = 169)	470:518	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	4	31	theme	clone	796:800	arg1	assays					812:817	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays	725:817	assays	812:817	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	2	32	theme	METHODS	314:320	arg1	staining					342:349	METHODS Immunohistochemical staining	314:349	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation	314:377	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	2	33	theme	normal	440:445	arg1	tissues					447:453	20 paired human bladder cancer and adjacent normal tissues	396:453	tissues	447:453	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	2	34	theme	bladder	476:482	arg1	cancer					484:489	human bladder cancer tissue microarrays (N = 169)	470:518	human bladder cancer tissue microarrays (N = 169)	470:518	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	0	35	theme	Suppressed	0:9	arg1	expression					15:24	Suppressed OGT expression	0:24	Suppressed OGT expression	0:24	Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer.
30453909	10	36	theme	cells	1537:1541	arg1	growth					1572:1577	xenograft tumor growth	1556:1577	xenograft tumor growth	1556:1577	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	10	36	theme	cells	1537:1541	arg1	proliferation					1505:1517	the proliferation	1501:1517	the proliferation of bladder cancer cells	1501:1541	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	14	37	gly	hyper-O-GlcNAcylation	1934:1954	arg1	response					2017:2024	DNA damage response	2006:2024	DNA damage response in bladder cancer	2006:2042	CONCLUSIONS The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.
30453909	9	38	theme	bladder	1369:1375	arg1	MIBC					1385:1388	MIBC	1385:1388	MIBC	1385:1388	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	38	theme	bladder	1369:1375	arg1	cancer					1377:1382	muscle-invasive bladder cancer	1353:1382	muscle-invasive bladder cancer (MIBC)	1353:1389	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	10	39	theme	bladder	1522:1528	arg1	cells					1537:1541	bladder cancer cells	1522:1541	bladder cancer cells	1522:1541	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	0	40	theme	cell	35:38	arg1	proliferation					40:52	cell proliferation	35:52	cell proliferation	35:52	Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer.
30453909	5	41	theme	Cell	820:823	arg1	apoptosis					825:833	Cell apoptosis	820:833	Cell apoptosis	820:833	Cell apoptosis and cell cycle analysis were detected using flow cytometry.
30453909	2	42	theme	tissue	491:496	arg1	N = 169					511:517	N = 169	511:517	N = 169	511:517	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	2	42	theme	tissue	491:496	arg1	microarrays					498:508	tissue microarrays	491:508	human bladder cancer tissue microarrays (N = 169)	470:518	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	10	43	theme	xenograft	1556:1564	arg1	growth					1572:1577	xenograft tumor growth	1556:1577	xenograft tumor growth	1556:1577	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	0	44	theme	cell	69:72	arg1	apoptosis					74:82	cell apoptosis	69:82	cell apoptosis	69:82	Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer.
30453909	1	45	theme	O-linked-β-N-acetylglucosamine	240:269	arg1	OGT					284:286	OGT	284:286	OGT	284:286	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	1	45	theme	O-linked-β-N-acetylglucosamine	240:269	arg1	transferase					271:281	O-linked-β-N-acetylglucosamine transferase	240:281	O-linked-β-N-acetylglucosamine transferase (OGT)	240:287	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	3	46	theme	O-GlcNAcylation	553:567	arg1	level					536:540	The expression level	521:540	The expression level of OGT and O-GlcNAcylation in cell lines	521:581	The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis.
30453909	14	47	theme	damage	2010:2015	arg1	response					2017:2024	DNA damage response	2006:2024	DNA damage response in bladder cancer	2006:2042	CONCLUSIONS The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.
30453909	2	48	theme	bladder	412:418	arg1	cancer					420:425	20 paired human bladder cancer and adjacent normal tissues	396:453	cancer	420:425	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	9	49	theme	bladder	1419:1425	arg1	NMIBC					1435:1439	NMIBC	1435:1439	NMIBC	1435:1439	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	49	theme	bladder	1419:1425	arg1	cancer					1427:1432	non-muscle-invasive bladder cancer	1399:1432	non-muscle-invasive bladder cancer (NMIBC)	1399:1440	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	6	50	theme	Western	960:966	arg1	analysis					973:980	the Western blot analysis	956:980	the Western blot analysis	956:980	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	13	51	theme	bladder	1860:1866	arg1	cells					1875:1879	bladder cancer cells	1860:1879	bladder cancer cells	1860:1879	Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum.
30453909	6	52	theme	bladder	912:918	arg1	cells					927:931	bladder cancer cells	912:931	bladder cancer cells	912:931	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	2	53	theme	paired	399:404	arg1	cancer					420:425	20 paired human bladder cancer and adjacent normal tissues	396:453	cancer	420:425	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	7	54	theme	cancer	1104:1109	arg1	cells					1111:1115	bladder cancer cells	1096:1115	bladder cancer cells	1096:1115	MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown.
30453909	13	55	theme	OGT	1810:1812	arg1	knockdown					1814:1822	OGT knockdown	1810:1822	OGT knockdown	1810:1822	Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum.
30453909	3	56	from	level	536:540	arg1	lines					577:581	cell lines	572:581	cell lines	572:581	The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis.
30453909	2	57	theme	Immunohistochemical	322:340	arg1	staining					342:349	METHODS Immunohistochemical staining	314:349	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation	314:377	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	1	58	theme	human	292:296	arg1	cancer					306:311	human bladder cancer	292:311	human bladder cancer	292:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	8	59	theme	OGT	1177:1179	arg1	expression					1163:1172	The expression	1159:1172	The expression of OGT	1159:1179	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	8	59	theme	OGT	1177:1179	arg1	RESULTS					1151:1157	RESULTS	1151:1157	RESULTS The expression of OGT and the O-GlcNAcylation	1151:1203	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	8	59	theme	OGT	1177:1179	arg1	O-GlcNAcylation					1189:1203	the O-GlcNAcylation	1185:1203	the O-GlcNAcylation	1185:1203	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	11	60	theme	cancer	1685:1690	arg1	cells					1692:1696	bladder cancer cells	1677:1696	bladder cancer cells	1677:1696	It also increased autophagy in bladder cancer cells.
30453909	6	61	theme	cancer	920:925	arg1	cells					927:931	bladder cancer cells	912:931	bladder cancer cells	912:931	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	14	62	dep	CONCLUSIONS	1898:1908	arg1	indicated					1919:1927	indicated	1919:1927	indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer	1919:2042	CONCLUSIONS The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.
30453909	1	63	from	cancer	306:311	arg1	elevation					209:217	an elevation	206:217	an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer	206:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	12	64	theme	pro-death	1765:1773	arg1	autophagy					1733:1741	increased autophagy	1723:1741	increased autophagy pro-survival, but not pro-death	1723:1773	This study demonstrated increased autophagy pro-survival, but not pro-death.
30453909	4	65	theme	bladder	690:696	arg1	cancer					698:703	bladder cancer	690:703	bladder cancer	690:703	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	14	66	theme	oncogenic	1965:1973	arg1	phenotypes					1975:1984	oncogenic phenotypes	1965:1984	oncogenic phenotypes	1965:1984	CONCLUSIONS The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.
30453909	4	67	theme	O-GlcNAcylation	645:659	arg1	effects					634:640	The effects	630:640	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer	630:703	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	3	68	theme	expression	525:534	arg1	level					536:540	The expression level	521:540	The expression level of OGT and O-GlcNAcylation in cell lines	521:581	The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis.
30453909	3	69	theme	blot	615:618	arg1	analysis					620:627	the Western blot analysis	603:627	the Western blot analysis	603:627	The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis.
30453909	9	70	gly	O-GlcNAcylation	1264:1278	arg1	cytoplasm					1317:1325	cytoplasm	1317:1325	cytoplasm	1317:1325	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	70	gly	O-GlcNAcylation	1264:1278	arg1	nucleus					1305:1311	nucleus	1305:1311	nucleus	1305:1311	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	5	71	theme	flow	879:882	arg1	cytometry					884:892	flow cytometry	879:892	flow cytometry	879:892	Cell apoptosis and cell cycle analysis were detected using flow cytometry.
30453909	8	72	theme	cancer	1233:1238	arg1	tissues					1240:1246	bladder cancer tissues	1225:1246	bladder cancer tissues	1225:1246	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	10	73	theme	cell	1627:1630	arg1	arrest					1638:1643	cell cycle arrest	1627:1643	cell cycle arrest	1627:1643	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	1	74	from	elevation	209:217	arg1	cancer					306:311	human bladder cancer	292:311	human bladder cancer	292:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	1	75	theme	hyper-O-linked	142:155	arg1	N-acetylglucosaminylation					157:181	hyper-O-linked N-acetylglucosaminylation	142:181	hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation)	142:199	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	1	75	theme	hyper-O-linked	142:155	arg1	O-GlcNAcylation					184:198	O-GlcNAcylation	184:198	O-GlcNAcylation	184:198	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	0	76	theme	bladder	87:93	arg1	cancer					95:100	bladder cancer	87:100	bladder cancer	87:100	Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer.
30453909	6	77	theme	autophagic	1026:1035	arg1	flux					1037:1040	the autophagic flux	1022:1040	the autophagic flux	1022:1040	The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP-LC3 plasmid was used to detect the autophagic flux.
30453909	4	78	theme	formation	802:810	arg1	assays					812:817	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays	725:817	assays	812:817	The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays.
30453909	2	79	theme	adjacent	431:438	arg1	tissues					447:453	20 paired human bladder cancer and adjacent normal tissues	396:453	tissues	447:453	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	5	80	theme	cell	839:842	arg1	analysis					850:857	cell cycle analysis	839:857	cell cycle analysis	839:857	Cell apoptosis and cell cycle analysis were detected using flow cytometry.
30453909	2	81	theme	human	470:474	arg1	cancer					484:489	human bladder cancer tissue microarrays (N = 169)	470:518	human bladder cancer tissue microarrays (N = 169)	470:518	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	8	82	dep	RESULTS	1151:1157	arg1	expression					1163:1172	The expression	1159:1172	The expression of OGT	1159:1179	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	8	82	dep	RESULTS	1151:1157	arg1	RESULTS					1151:1157	RESULTS	1151:1157	RESULTS The expression of OGT and the O-GlcNAcylation	1151:1203	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	8	82	dep	RESULTS	1151:1157	arg1	O-GlcNAcylation					1189:1203	the O-GlcNAcylation	1185:1203	the O-GlcNAcylation	1185:1203	RESULTS The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines.
30453909	13	83	theme	cells	1875:1879	arg1	chemosensitivity					1840:1855	the chemosensitivity	1836:1855	the chemosensitivity of bladder cancer cells to cis-platinum	1836:1895	Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum.
30453909	9	84	theme	muscle-invasive	1353:1367	arg1	MIBC					1385:1388	MIBC	1385:1388	MIBC	1385:1388	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	84	theme	muscle-invasive	1353:1367	arg1	cancer					1377:1382	muscle-invasive bladder cancer	1353:1382	muscle-invasive bladder cancer (MIBC)	1353:1389	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	10	85	theme	cancer	1530:1535	arg1	cells					1537:1541	bladder cancer cells	1522:1541	bladder cancer cells	1522:1541	Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest.
30453909	1	86	theme	expression	226:235	arg1	elevation					209:217	an elevation	206:217	an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer	206:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	1	87	theme	transferase	271:281	arg1	expression					226:235	the expression	222:235	the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer	222:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	14	88	theme	bladder	2029:2035	arg1	cancer					2037:2042	bladder cancer	2029:2042	bladder cancer	2029:2042	CONCLUSIONS The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.
30453909	2	89	theme	human	406:410	arg1	cancer					420:425	20 paired human bladder cancer and adjacent normal tissues	396:453	cancer	420:425	METHODS Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169).
30453909	1	90	from	expression	226:235	arg1	cancer					306:311	human bladder cancer	292:311	human bladder cancer	292:311	BACKGROUND This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.
30453909	3	91	theme	OGT	545:547	arg1	level					536:540	The expression level	521:540	The expression level of OGT and O-GlcNAcylation in cell lines	521:581	The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis.
30453909	9	92	theme	non-muscle-invasive	1399:1417	arg1	NMIBC					1435:1439	NMIBC	1435:1439	NMIBC	1435:1439	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	9	92	theme	non-muscle-invasive	1399:1417	arg1	cancer					1427:1432	non-muscle-invasive bladder cancer	1399:1432	non-muscle-invasive bladder cancer (NMIBC)	1399:1440	O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC).
30453909	14	93	theme	DNA	2006:2008	arg1	damage					2010:2015	DNA damage	2006:2015	DNA damage response in bladder cancer	2006:2042	CONCLUSIONS The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.
30453909	0	94	theme	OGT	11:13	arg1	expression					15:24	Suppressed OGT expression	0:24	Suppressed OGT expression	0:24	Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer.
30619255	7	0	theme	PNA-reactive	1127:1138	arg1	O-glycans					1140:1148	PNA-reactive O-glycans	1127:1148	PNA-reactive O-glycans	1127:1148	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	9	1	theme	naïve/GC	1787:1794	arg1	subsets					1796:1802	naïve/GC subsets	1787:1802	naïve/GC subsets	1787:1802	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	10	2	theme	significant	1983:1993	arg1	loss					1995:1998	significant loss	1983:1998	significant loss	1983:1998	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	10	3	theme	primary	1862:1868	arg1	cell					1872:1875	primary B cell	1862:1875	primary B cell binding to B220, MEM55, and several plant lectins	1862:1925	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	12	4	gly	glycoforms	2443:2452	arg1	O-glycosylation					2415:2429	distinct O-glycosylation states/CD45 glycoforms	2406:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	12	4	gly	glycoforms	2443:2452	arg1	states/CD45					2431:2441	distinct O-glycosylation states/CD45 glycoforms	2406:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	1	5	theme	antibody-secreting	258:275	arg1	cells					284:288	antibody-secreting plasma cells	258:288	antibody-secreting plasma cells	258:288	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	9	6	theme	altered	1608:1614	arg1	binding					1616:1622	altered binding	1608:1622	altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively	1608:1847	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	6	7	theme	B	1064:1064	arg1	lines					1071:1075	B cell lines	1064:1075	B cell lines	1064:1075	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	10	8	theme	complexity	2012:2021	arg1	loss					1995:1998	significant loss	1983:1998	significant loss	1983:1998	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	2	9	theme	GC	304:305	arg1	cells					309:313	GC B cells	304:313	GC B cells	304:313	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	1	10	theme	antibody	177:184	arg1	maturation					195:204	antibody affinity maturation	177:204	antibody affinity maturation	177:204	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	6	11	theme	cell	889:892	arg1	binding					894:900	GC B cell binding	884:900	GC B cell binding to PNA	884:907	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	10	12	theme	Core	2051:2054	arg1	O-glycans					2058:2066	extended Core 2 O-glycans	2042:2066	extended Core 2 O-glycans	2042:2066	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	10	13	theme	cell	1872:1875	arg1	Analysis					1850:1857	Analysis	1850:1857	Analysis of primary B cell binding to B220, MEM55, and several plant lectins	1850:1925	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	8	14	from	reports	1337:1343	arg1	cells					1350:1354	T cells	1348:1354	T cells	1348:1354	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	12	15	from	stage	2462:2466	arg1	expression					2392:2401	expression	2392:2401	expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation	2392:2492	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	3	16	attach	linked	619:624	arg2	acquisition					547:557	acquisition	547:557	acquisition of PNA binding by activated T cells and thymocytes	547:608	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	3	16	attach	linked	619:624	arg3	cells					540:544	T cells	538:544	T cells	538:544	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	6	17	theme	GC	884:885	arg1	binding					894:900	GC B cell binding	884:900	GC B cell binding to PNA	884:907	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	9	18	theme	glycosylation-sensitive	1631:1653	arg1	MEM55					1712:1716	MEM55	1712:1716	MEM55	1712:1716	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	9	18	theme	glycosylation-sensitive	1631:1653	arg1	RA3-6B2					1672:1678	RA3-6B2	1672:1678	RA3-6B2 (more commonly called B220)	1672:1706	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	9	18	theme	glycosylation-sensitive	1631:1653	arg1	antibodies					1660:1669	two glycosylation-sensitive CD45 antibodies	1627:1669	two glycosylation-sensitive CD45 antibodies	1627:1669	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	7	19	theme	antigen	1285:1291	arg1	signaling					1302:1310	antigen receptor signaling	1285:1310	antigen receptor signaling	1285:1310	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	9	20	theme	antibodies	1660:1669	arg1	binding					1616:1622	altered binding	1608:1622	altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively	1608:1847	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	8	21	theme	ST3Gal1	1357:1363	arg1	overexpression					1365:1378	ST3Gal1 overexpression	1357:1378	ST3Gal1 overexpression in B cells in vitro	1357:1398	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	3	22	theme	PNA	562:564	arg1	binding					566:572	PNA binding	562:572	PNA binding	562:572	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	5	23	theme	GC	858:859	arg1	cells					863:867	GC B cells	858:867	GC B cells	858:867	Here, we investigated the basis for PNA reactivity of GC B cells.
30619255	10	24	theme	O-glycans	2058:2066	arg1	loss					2034:2037	loss	2034:2037	loss of extended Core 2 O-glycans	2034:2066	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	1	25	theme	microanatomical	119:133	arg1	centers					102:108	Germinal centers	93:108	Germinal centers (GC)	93:113	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	1	25	theme	microanatomical	119:133	arg1	niches					135:140	microanatomical niches	119:140	microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells	119:288	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	2	26	theme	disaccharide	473:484	arg1	Gal-β1,3-GalNAc-Ser/Thr					486:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr	457:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	457:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	11	27	theme	GCNT1	2231:2235	arg1	downregulation					2185:2198	downregulation	2185:2198	downregulation of the Core 2 branching enzyme GCNT1	2185:2235	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	10	28	theme	several	1905:1911	arg1	lectins					1919:1925	several plant lectins	1905:1925	several plant lectins	1905:1925	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	3	29	theme	T	587:587	arg1	cells					589:593	activated T cells	577:593	activated T cells	577:593	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	9	30	theme	called	1695:1700	arg1	B220					1702:1705	more commonly called B220	1681:1705	more commonly called B220	1681:1705	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	9	30	theme	called	1695:1700	arg1	RA3-6B2					1672:1678	RA3-6B2	1672:1678	RA3-6B2 (more commonly called B220)	1672:1706	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	10	31	theme	cell	1944:1947	arg1	differentiation					1949:1963	B cell differentiation	1942:1963	B cell differentiation	1942:1963	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	0	32	theme	O-Linked	75:82	arg1	Glycans					84:90	O-Linked Glycans	75:90	O-Linked Glycans	75:90	Human B Cell Differentiation Is Characterized by Progressive Remodeling of O-Linked Glycans.
30619255	8	33	theme	drastic	1408:1414	arg1	shortening					1416:1425	drastic shortening	1408:1425	drastic shortening	1408:1425	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	12	34	theme	B	2471:2471	arg1	differentiation					2478:2492	B cell differentiation	2471:2492	B cell differentiation	2471:2492	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	5	35	theme	cells	863:867	arg1	reactivity					844:853	PNA reactivity	840:853	PNA reactivity of GC B cells	840:867	Here, we investigated the basis for PNA reactivity of GC B cells.
30619255	11	36	theme	post-GC	2126:2132	arg1	fates					2134:2138	post-GC fates	2126:2138	post-GC fates	2126:2138	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	12	37	theme	differentiation	2478:2492	arg1	stage					2462:2466	each stage	2457:2466	each stage of B cell differentiation	2457:2492	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	2	38	theme	peanut	373:378	arg1	PNA					392:394	PNA	392:394	PNA	392:394	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	2	38	theme	peanut	373:378	arg1	agglutinin					380:389	the plant lectin peanut agglutinin	356:389	the plant lectin peanut agglutinin (PNA)	356:395	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	2	39	theme	serine/threonine	410:425	arg1	glycans					438:444	serine/threonine (O-linked) glycans	410:444	serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	410:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	2	40	theme	plant	360:364	arg1	PNA					392:394	PNA	392:394	PNA	392:394	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	2	40	theme	plant	360:364	arg1	agglutinin					380:389	the plant lectin peanut agglutinin	356:389	the plant lectin peanut agglutinin (PNA)	356:395	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	0	41	theme	Human	0:4	arg1	Differentiation					13:27	Human B Cell Differentiation	0:27	Human B Cell Differentiation	0:27	Human B Cell Differentiation Is Characterized by Progressive Remodeling of O-Linked Glycans.
30619255	1	42	theme	plasma	277:282	arg1	cells					284:288	antibody-secreting plasma cells	258:288	antibody-secreting plasma cells	258:288	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	1	43	theme	Germinal	93:100	arg1	GC					111:112	GC	111:112	GC	111:112	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	1	43	theme	Germinal	93:100	arg1	centers					102:108	Germinal centers	93:108	Germinal centers (GC)	93:113	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	1	43	theme	Germinal	93:100	arg1	niches					135:140	microanatomical niches	119:140	microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells	119:288	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	12	44	theme	cell	2304:2307	arg1	differentiation					2309:2323	B cell differentiation	2302:2323	B cell differentiation	2302:2323	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	4	45	theme	GC	701:702	arg1	cells					706:710	GC B cells	701:710	GC B cells	701:710	Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved.
30619255	0	46	theme	Cell	8:11	arg1	Differentiation					13:27	Human B Cell Differentiation	0:27	Human B Cell Differentiation	0:27	Human B Cell Differentiation Is Characterized by Progressive Remodeling of O-Linked Glycans.
30619255	2	47	dep	Gal-β1,3-GalNAc-Ser/Thr	486:508	arg1	called					516:521	called	516:521	called T-antigen	516:531	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	7	48	theme	tyrosine	1209:1216	arg1	scaffold					1114:1121	the primary scaffold	1102:1121	the primary scaffold for PNA-reactive O-glycans in B cells	1102:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	7	48	theme	tyrosine	1209:1216	arg1	phosphatase					1218:1228	the B cell receptor-associated receptor-type tyrosine phosphatase	1164:1228	the B cell receptor-associated receptor-type tyrosine phosphatase CD45	1164:1233	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	11	49	theme	decreased	2086:2094	arg1	length					2105:2110	decreased O-glycan length	2086:2110	decreased O-glycan length from naïve to post-GC fates	2086:2138	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	6	50	theme	sialyltransferase	955:971	arg1	downregulation					928:941	downregulation	928:941	downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1)	928:990	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	4	51	theme	PNA	759:761	arg1	binding					763:769	PNA binding	759:769	PNA binding	759:769	Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved.
30619255	7	52	theme	receptor-associated	1175:1193	arg1	scaffold					1114:1121	the primary scaffold	1102:1121	the primary scaffold for PNA-reactive O-glycans in B cells	1102:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	7	52	theme	receptor-associated	1175:1193	arg1	phosphatase					1218:1228	the B cell receptor-associated receptor-type tyrosine phosphatase	1164:1228	the B cell receptor-associated receptor-type tyrosine phosphatase CD45	1164:1233	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	2	53	theme	O-linked	428:435	arg1	glycans					438:444	serine/threonine (O-linked) glycans	410:444	serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	410:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	8	54	theme	antibody	1468:1475	arg1	staining					1477:1484	antibody staining	1468:1484	antibody staining	1468:1484	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	7	55	theme	B	1168:1168	arg1	scaffold					1114:1121	the primary scaffold	1102:1121	the primary scaffold for PNA-reactive O-glycans in B cells	1102:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	7	55	theme	B	1168:1168	arg1	phosphatase					1218:1228	the B cell receptor-associated receptor-type tyrosine phosphatase	1164:1228	the B cell receptor-associated receptor-type tyrosine phosphatase CD45	1164:1233	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	12	56	theme	O-glycosylation	2415:2429	arg1	glycoforms					2443:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	3	57	theme	homing	646:651	arg1	patterns					653:660	altered tissue homing patterns	631:660	altered tissue homing patterns	631:660	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	12	58	theme	glycoforms	2443:2452	arg1	expression					2392:2401	expression	2392:2401	expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation	2392:2492	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	8	59	theme	spectrometric	1495:1507	arg1	analysis					1520:1527	mass spectrometric O-glycomic analysis	1490:1527	mass spectrometric O-glycomic analysis	1490:1527	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	6	60	theme	α2,3	950:953	arg1	ST3GAL1					974:980	ST3GAL1	974:980	ST3GAL1 (ST3Gal1)	974:990	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	6	60	theme	α2,3	950:953	arg1	sialyltransferase					955:971	the α2,3 sialyltransferase	946:971	the α2,3 sialyltransferase	946:971	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	8	61	theme	T	1348:1348	arg1	cells					1350:1354	T cells	1348:1354	T cells	1348:1354	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	1	62	theme	long-lived	228:237	arg1	cells					248:252	long-lived memory B cells	228:252	long-lived memory B cells	228:252	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	7	63	theme	B	1153:1153	arg1	cells					1155:1159	B cells	1153:1159	B cells	1153:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	10	64	theme	O-glycan	2003:2010	arg1	complexity					2012:2021	O-glycan complexity	2003:2021	O-glycan complexity	2003:2021	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	1	65	theme	B	246:246	arg1	cells					248:252	long-lived memory B cells	228:252	long-lived memory B cells	228:252	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	9	66	theme	O-glycan	1571:1578	arg1	length					1580:1585	O-glycan length	1571:1585	O-glycan length	1571:1585	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	11	67	theme	enzyme	2224:2229	arg1	GCNT1					2231:2235	the Core 2 branching enzyme GCNT1	2203:2235	the Core 2 branching enzyme GCNT1	2203:2235	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	9	68	dep	which	1719:1723	arg1	humans					1729:1734	humans	1729:1734	humans	1729:1734	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	8	69	dep	induced	1400:1406	arg1	confirmed					1450:1458	confirmed	1450:1458	confirmed by both antibody staining and mass spectrometric O-glycomic analysis	1450:1527	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	5	70	theme	PNA	840:842	arg1	reactivity					844:853	PNA reactivity	840:853	PNA reactivity of GC B cells	840:867	Here, we investigated the basis for PNA reactivity of GC B cells.
30619255	9	71	theme	memory/plasmablast	1808:1825	arg1	subsets					1827:1833	memory/plasmablast subsets	1808:1833	memory/plasmablast subsets	1808:1833	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	6	72	theme	cell	1066:1069	arg1	lines					1071:1075	B cell lines	1064:1075	B cell lines	1064:1075	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	12	73	theme	B	2302:2302	arg1	differentiation					2309:2323	B cell differentiation	2302:2323	B cell differentiation	2302:2323	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	7	74	theme	primary	1106:1112	arg1	scaffold					1114:1121	the primary scaffold	1102:1121	the primary scaffold for PNA-reactive O-glycans in B cells	1102:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	7	74	theme	primary	1106:1112	arg1	phosphatase					1218:1228	the B cell receptor-associated receptor-type tyrosine phosphatase	1164:1228	the B cell receptor-associated receptor-type tyrosine phosphatase CD45	1164:1233	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	2	75	theme	B	307:307	arg1	cells					309:313	GC B cells	304:313	GC B cells	304:313	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	4	76	dep	basis	733:737	arg1	the					713:715	the	713:715	the	713:715	Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved.
30619255	8	77	with	Consistent	1313:1322	arg1	reports					1337:1343	similar reports	1329:1343	similar reports in T cells	1329:1354	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	3	78	theme	T	538:538	arg1	cells					540:544	T cells	538:544	T cells	538:544	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	1	79	theme	affinity	186:193	arg1	maturation					195:204	antibody affinity maturation	177:204	antibody affinity maturation	177:204	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	6	80	theme	B	887:887	arg1	binding					894:900	GC B cell binding	884:900	GC B cell binding to PNA	884:907	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	6	81	theme	PNA	1049:1051	arg1	binding					1053:1059	PNA binding	1049:1059	PNA binding	1049:1059	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	10	82	theme	extended	2042:2049	arg1	O-glycans					2058:2066	extended Core 2 O-glycans	2042:2066	extended Core 2 O-glycans	2042:2066	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	10	83	theme	B	1870:1870	arg1	cell					1872:1875	primary B cell	1862:1875	primary B cell binding to B220, MEM55, and several plant lectins	1862:1925	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	3	84	theme	binding	566:572	arg1	acquisition					547:557	acquisition	547:557	acquisition of PNA binding by activated T cells and thymocytes	547:608	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	9	85	theme	CD45	1655:1658	arg1	MEM55					1712:1716	MEM55	1712:1716	MEM55	1712:1716	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	9	85	theme	CD45	1655:1658	arg1	RA3-6B2					1672:1678	RA3-6B2	1672:1678	RA3-6B2 (more commonly called B220)	1672:1706	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	9	85	theme	CD45	1655:1658	arg1	antibodies					1660:1669	two glycosylation-sensitive CD45 antibodies	1627:1669	two glycosylation-sensitive CD45 antibodies	1627:1669	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	7	86	theme	receptor	1293:1300	arg1	signaling					1302:1310	antigen receptor signaling	1285:1310	antigen receptor signaling	1285:1310	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	8	87	theme	B	1383:1383	arg1	cells					1385:1389	B cells	1383:1389	B cells	1383:1389	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	5	88	theme	B	861:861	arg1	cells					863:867	GC B cells	858:867	GC B cells	858:867	Here, we investigated the basis for PNA reactivity of GC B cells.
30619255	7	89	from	scaffold	1114:1121	arg1	cells					1155:1159	B cells	1153:1159	B cells	1153:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	7	90	theme	altered	1258:1264	arg1	O-glycosylation					1266:1280	altered O-glycosylation	1258:1280	altered O-glycosylation	1258:1280	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	10	91	theme	plant	1913:1917	arg1	lectins					1919:1925	several plant lectins	1905:1925	several plant lectins	1905:1925	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	8	92	from	overexpression	1365:1378	arg1	cells					1385:1389	B cells	1383:1389	B cells	1383:1389	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	3	93	theme	activated	577:585	arg1	cells					589:593	activated T cells	577:593	activated T cells	577:593	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	12	94	theme	distinct	2406:2413	arg1	glycoforms					2443:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	2	95	theme	asialylated	461:471	arg1	Gal-β1,3-GalNAc-Ser/Thr					486:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr	457:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	457:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	12	96	theme	O-glycan	2266:2273	arg1	remodeling					2275:2284	O-glycan remodeling	2266:2284	O-glycan remodeling	2266:2284	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	12	96	theme	O-glycan	2266:2273	arg1	feature					2291:2297	a feature	2289:2297	a feature	2289:2297	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	0	97	theme	Glycans	84:90	arg1	Remodeling					61:70	Progressive Remodeling	49:70	Progressive Remodeling of O-Linked Glycans	49:90	Human B Cell Differentiation Is Characterized by Progressive Remodeling of O-Linked Glycans.
30619255	1	98	theme	B	148:148	arg1	cells					150:154	B cells	148:154	B cells	148:154	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30619255	12	99	theme	cell	2473:2476	arg1	differentiation					2478:2492	B cell differentiation	2471:2492	B cell differentiation	2471:2492	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	10	100	theme	B	1942:1942	arg1	differentiation					1949:1963	B cell differentiation	1942:1963	B cell differentiation	1942:1963	Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans.
30619255	4	101	theme	glycobiological	717:731	arg1	basis					733:737	glycobiological basis	717:737	glycobiological basis	717:737	Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved.
30619255	4	102	theme	B	704:704	arg1	cells					706:710	GC B cells	701:710	GC B cells	701:710	Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved.
30619255	7	103	from	role	1249:1252	arg1	signaling					1302:1310	antigen receptor signaling	1285:1310	antigen receptor signaling	1285:1310	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	2	104	link	O-linked	428:435	arg1	glycans					438:444	serine/threonine (O-linked) glycans	410:444	serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	410:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	2	105	theme	lectin	366:371	arg1	PNA					392:394	PNA	392:394	PNA	392:394	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	2	105	theme	lectin	366:371	arg1	agglutinin					380:389	the plant lectin peanut agglutinin	356:389	the plant lectin peanut agglutinin (PNA)	356:395	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	0	106	theme	B	6:6	arg1	Differentiation					13:27	Human B Cell Differentiation	0:27	Human B Cell Differentiation	0:27	Human B Cell Differentiation Is Characterized by Progressive Remodeling of O-Linked Glycans.
30619255	2	107	gly	asialylated	461:471	arg1	Gal-β1,3-GalNAc-Ser/Thr					486:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr	457:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	457:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	12	108	theme	differentiation	2309:2323	arg1	remodeling					2275:2284	O-glycan remodeling	2266:2284	O-glycan remodeling	2266:2284	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	12	108	theme	differentiation	2309:2323	arg1	feature					2291:2297	a feature	2289:2297	a feature	2289:2297	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	3	109	theme	altered	631:637	arg1	patterns					653:660	altered tissue homing patterns	631:660	altered tissue homing patterns	631:660	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	7	110	theme	receptor-type	1195:1207	arg1	scaffold					1114:1121	the primary scaffold	1102:1121	the primary scaffold for PNA-reactive O-glycans in B cells	1102:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	7	110	theme	receptor-type	1195:1207	arg1	phosphatase					1218:1228	the B cell receptor-associated receptor-type tyrosine phosphatase	1164:1228	the B cell receptor-associated receptor-type tyrosine phosphatase CD45	1164:1233	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	9	111	from	changes	1560:1566	arg1	length					1580:1585	O-glycan length	1571:1585	O-glycan length	1571:1585	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	2	112	dep	called	516:521	arg1	also					511:514	also	511:514	also	511:514	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	7	113	dep	phosphatase	1218:1228	arg1	CD45					1230:1233	CD45	1230:1233	the B cell receptor-associated receptor-type tyrosine phosphatase CD45	1164:1233	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	12	114	theme	states/CD45	2431:2441	arg1	glycoforms					2443:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	distinct O-glycosylation states/CD45 glycoforms	2406:2452	Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.
30619255	7	115	theme	cell	1170:1173	arg1	scaffold					1114:1121	the primary scaffold	1102:1121	the primary scaffold for PNA-reactive O-glycans in B cells	1102:1159	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	7	115	theme	cell	1170:1173	arg1	phosphatase					1218:1228	the B cell receptor-associated receptor-type tyrosine phosphatase	1164:1228	the B cell receptor-associated receptor-type tyrosine phosphatase CD45	1164:1233	Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling.
30619255	11	116	theme	O-glycan	2096:2103	arg1	length					2105:2110	decreased O-glycan length	2086:2110	decreased O-glycan length from naïve to post-GC fates	2086:2138	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	2	117	contain	containing	446:455	arg2	Gal-β1,3-GalNAc-Ser/Thr					486:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr	457:508	the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	457:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	2	117	contain	containing	446:455	arg1	glycans					438:444	serine/threonine (O-linked) glycans	410:444	serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen)	410:532	For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen).
30619255	0	118	theme	Progressive	49:59	arg1	Remodeling					61:70	Progressive Remodeling	49:70	Progressive Remodeling of O-Linked Glycans	49:90	Human B Cell Differentiation Is Characterized by Progressive Remodeling of O-Linked Glycans.
30619255	8	119	theme	mass	1490:1493	arg1	analysis					1520:1527	mass spectrometric O-glycomic analysis	1490:1527	mass spectrometric O-glycomic analysis	1490:1527	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	3	120	theme	tissue	639:644	arg1	patterns					653:660	altered tissue homing patterns	631:660	altered tissue homing patterns	631:660	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	4	121	theme	binding	763:769	arg1	significance					743:754	significance	743:754	significance	743:754	Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved.
30619255	4	121	theme	binding	763:769	arg1	basis					733:737	glycobiological basis	717:737	glycobiological basis	717:737	Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved.
30619255	11	122	theme	branching	2214:2222	arg1	GCNT1					2231:2235	the Core 2 branching enzyme GCNT1	2203:2235	the Core 2 branching enzyme GCNT1	2203:2235	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	8	123	theme	O-glycomic	1509:1518	arg1	analysis					1520:1527	mass spectrometric O-glycomic analysis	1490:1527	mass spectrometric O-glycomic analysis	1490:1527	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	11	124	from	naïve	2117:2121	arg1	length					2105:2110	decreased O-glycan length	2086:2110	decreased O-glycan length from naïve to post-GC fates	2086:2138	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	8	125	theme	similar	1329:1335	arg1	reports					1337:1343	similar reports	1329:1343	similar reports in T cells	1329:1354	Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis.
30619255	9	126	theme	ST3Gal1-induced	1544:1558	arg1	changes					1560:1566	ST3Gal1-induced changes	1544:1566	ST3Gal1-induced changes in O-glycan length	1544:1585	Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively.
30619255	6	127	theme	ST3Gal1	1015:1021	arg1	overexpression					997:1010	overexpression	997:1010	overexpression of ST3Gal1	997:1021	We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines.
30619255	11	128	theme	Core	2207:2210	arg1	GCNT1					2231:2235	the Core 2 branching enzyme GCNT1	2203:2235	the Core 2 branching enzyme GCNT1	2203:2235	To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1.
30619255	3	129	theme	cell	663:666	arg1	signaling					668:676	cell signaling	663:676	cell signaling	663:676	In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival.
30619255	1	130	theme	memory	239:244	arg1	cells					248:252	long-lived memory B cells	228:252	long-lived memory B cells	228:252	Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells.
30889014	12	0	from	PNGSs	1769:1773	arg1	V4					1785:1786	V4	1785:1786	V4	1785:1786	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	0	from	PNGSs	1769:1773	arg1	V3					1778:1779	V3	1778:1779	V3	1778:1779	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	11	1	theme	HIV-1	1610:1614	arg1	genotype					1616:1623	HIV-1 genotype	1610:1623	HIV-1 genotype	1610:1623	CONCLUSION CRF01_AE has dominated HIV-1 genotype in Northeast China.
30889014	6	2	theme	site	898:901	arg1	number					910:915	Potential N-linked glycosylation site (PNGS) number	865:915	Potential N-linked glycosylation site (PNGS) number	865:915	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	1	3	theme	recombinant	291:301	arg1	strains					320:326	circulating recombinant form (CRF) 01_AE strains	279:326	circulating recombinant form (CRF) 01_AE strains in Northeast China	279:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	12	4	theme	specific	1736:1743	arg1	region					1831:1836	V4 region	1828:1836	V4 region	1828:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	4	theme	specific	1736:1743	arg1	residues					1756:1763	specific amino acid residues	1736:1763	specific amino acid residues	1736:1763	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	10	5	from	PNGSs	1282:1286	arg1	V4					1341:1342	V4	1341:1342	V4	1341:1342	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	6	theme	coreceptor	1538:1547	arg1	usage					1549:1553	the X4/R5X4 coreceptor usage	1526:1553	the X4/R5X4 coreceptor usage of CRF01_AE viruses	1526:1573	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	6	7	theme	N-linked	875:882	arg1	PNGS					904:907	PNGS	904:907	PNGS	904:907	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	6	7	theme	N-linked	875:882	arg1	site					898:901	Potential N-linked glycosylation site	865:901	Potential N-linked glycosylation site (PNGS) number	865:915	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	3	8	theme	coreceptor	588:597	arg1	usages					599:604	different coreceptor usages	578:604	different coreceptor usages	578:604	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	9	9	with	samples	1197:1203	arg1	count					1219:1223	CD4 cell count	1210:1223	CD4 cell count less than 200 cells/μl	1210:1246	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	12	10	theme	acid	1751:1754	arg1	region					1831:1836	V4 region	1828:1836	V4 region	1828:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	10	theme	acid	1751:1754	arg1	residues					1756:1763	specific amino acid residues	1736:1763	specific amino acid residues	1736:1763	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	1	11	from	strains	320:326	arg1	China					341:345	Northeast China	331:345	Northeast China	331:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	10	12	theme	Val21	1428:1432	arg1	presence					1445:1452	presence	1445:1452	presence of more than 4 of net charges	1445:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	12	theme	Val21	1428:1432	arg1	coexistence					1399:1409	coexistence	1399:1409	coexistence	1399:1409	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	12	theme	Val21	1428:1432	arg1	lack					1488:1491	lack	1488:1491	lack of the PNGS within V3	1488:1513	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	12	theme	Val21	1428:1432	arg1	existence					1386:1394	existence	1386:1394	existence	1386:1394	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	6	13	theme	online	942:947	arg1	software					961:968	the online N-glycosite software	938:968	the online N-glycosite software	938:968	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	0	14	link	N-linked	43:50	arg1	sites					66:70	potential N-linked glycosylation sites	33:70	potential N-linked glycosylation sites	33:70	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	10	15	theme	viruses	1567:1573	arg1	usage					1549:1553	the X4/R5X4 coreceptor usage	1526:1553	the X4/R5X4 coreceptor usage of CRF01_AE viruses	1526:1573	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	16	theme	Arg13	1421:1425	arg1	presence					1445:1452	presence	1445:1452	presence of more than 4 of net charges	1445:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	16	theme	Arg13	1421:1425	arg1	coexistence					1399:1409	coexistence	1399:1409	coexistence	1399:1409	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	16	theme	Arg13	1421:1425	arg1	lack					1488:1491	lack	1488:1491	lack of the PNGS within V3	1488:1513	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	16	theme	Arg13	1421:1425	arg1	existence					1386:1394	existence	1386:1394	existence	1386:1394	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	1	17	theme	epidemiological	202:216	arg1	feature					218:224	epidemiological feature	202:224	epidemiological feature	202:224	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	8	18	theme	main	1082:1085	arg1	genotype					1093:1100	the main HIV-1 genotype	1078:1100	the main HIV-1 genotype since 2010	1078:1111	RESULTS CRF01_AE become the main HIV-1 genotype since 2010.
30889014	10	19	theme	Thr12	1414:1418	arg1	presence					1445:1452	presence	1445:1452	presence of more than 4 of net charges	1445:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	19	theme	Thr12	1414:1418	arg1	coexistence					1399:1409	coexistence	1399:1409	coexistence	1399:1409	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	19	theme	Thr12	1414:1418	arg1	lack					1488:1491	lack	1488:1491	lack of the PNGS within V3	1488:1513	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	19	theme	Thr12	1414:1418	arg1	existence					1386:1394	existence	1386:1394	existence	1386:1394	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	20	theme	amino	1257:1261	arg1	length					1268:1273	Shorter amino acid length	1249:1273	Shorter amino acid length	1249:1273	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	12	21	from	length	1818:1823	arg1	V4					1785:1786	V4	1785:1786	V4	1785:1786	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	21	from	length	1818:1823	arg1	V3					1778:1779	V3	1778:1779	V3	1778:1779	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	10	22	from	length	1268:1273	arg1	V4					1341:1342	V4	1341:1342	V4	1341:1342	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	4	23	theme	identified	732:741	arg1	strains					743:749	newly identified strains	726:749	newly identified strains	726:749	METHODS The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06.
30889014	6	24	gly	N-glycosite	949:959	arg2	N-glycosite					949:959	the online N-glycosite software	938:968	the online N-glycosite software	938:968	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	10	25	theme	acid	1263:1266	arg1	length					1268:1273	Shorter amino acid length	1249:1273	Shorter amino acid length	1249:1273	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	7	26	theme	online	1031:1036	arg1	tool					1048:1051	the online ProtParam tool	1027:1051	the online ProtParam tool	1027:1051	The properties of amino acid sequences were analyzed by the online ProtParam tool.
30889014	12	27	theme	fast	1681:1684	arg1	progression					1694:1704	a fast disease progression	1679:1704	a fast disease progression	1679:1704	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	10	28	theme	Lys33	1438:1442	arg1	presence					1445:1452	presence	1445:1452	presence of more than 4 of net charges	1445:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	28	theme	Lys33	1438:1442	arg1	coexistence					1399:1409	coexistence	1399:1409	coexistence	1399:1409	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	28	theme	Lys33	1438:1442	arg1	lack					1488:1491	lack	1488:1491	lack of the PNGS within V3	1488:1513	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	28	theme	Lys33	1438:1442	arg1	existence					1386:1394	existence	1386:1394	existence	1386:1394	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	0	29	theme	recombinant	98:108	arg1	pathogenesis					121:132	circulating recombinant form 01_AE pathogenesis	86:132	circulating recombinant form 01_AE pathogenesis in Northeast China	86:151	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	10	30	theme	4	1467:1467	arg1	presence					1445:1452	presence	1445:1452	presence of more than 4 of net charges	1445:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	30	theme	4	1467:1467	arg1	coexistence					1399:1409	coexistence	1399:1409	coexistence	1399:1409	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	30	theme	4	1467:1467	arg1	lack					1488:1491	lack	1488:1491	lack of the PNGS within V3	1488:1513	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	30	theme	4	1467:1467	arg1	existence					1386:1394	existence	1386:1394	existence	1386:1394	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	3	31	theme	Further	478:484	arg1	analyses					486:493	Further analyses	478:493	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages	478:604	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	0	32	theme	01_AE	115:119	arg1	pathogenesis					121:132	circulating recombinant form 01_AE pathogenesis	86:132	circulating recombinant form 01_AE pathogenesis in Northeast China	86:151	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	0	33	theme	potential	33:41	arg1	sites					66:70	potential N-linked glycosylation sites	33:70	potential N-linked glycosylation sites	33:70	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	10	34	theme	motif	1316:1320	arg1	R/KNXT					1322:1327	a basic motif R/KNXT	1308:1327	a basic motif R/KNXT	1308:1327	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	0	35	theme	Critical	0:7	arg1	residues					20:27	Critical amino acid residues	0:27	Critical amino acid residues	0:27	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	1	36	theme	CRF	309:311	arg1	strains					320:326	circulating recombinant form (CRF) 01_AE strains	279:326	circulating recombinant form (CRF) 01_AE strains in Northeast China	279:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	7	37	theme	acid	995:998	arg1	sequences					1000:1008	amino acid sequences	989:1008	amino acid sequences	989:1008	The properties of amino acid sequences were analyzed by the online ProtParam tool.
30889014	1	38	dep	OBJECTIVE	154:162	arg1	aimed					182:186	aimed	182:186	aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China	182:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	0	39	theme	acid	15:18	arg1	residues					20:27	Critical amino acid residues	0:27	Critical amino acid residues	0:27	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	1	40	theme	01_AE	314:318	arg1	strains					320:326	circulating recombinant form (CRF) 01_AE strains	279:326	circulating recombinant form (CRF) 01_AE strains in Northeast China	279:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	10	41	theme	net	1472:1474	arg1	charges					1476:1482	net charges	1472:1482	net charges	1472:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	42	theme	fewer	1276:1280	arg1	PNGSs					1282:1286	fewer PNGSs	1276:1286	fewer PNGSs	1276:1286	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	2	43	theme	pathogenicity	442:454	arg1	features					456:463	the pathogenicity features	438:463	the pathogenicity features of CRF01_AE	438:475	DESIGN Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE.
30889014	5	44	theme	Geno2Pheno	843:852	arg1	algorithm					854:862	Geno2Pheno algorithm	843:862	Geno2Pheno algorithm	843:862	Coreceptor usage was predicted by Geno2Pheno algorithm.
30889014	12	45	theme	V4	1828:1829	arg1	region					1831:1836	V4 region	1828:1836	V4 region	1828:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	46	with	Infection	1645:1653	arg1	CRF01_AE					1660:1667	CRF01_AE	1660:1667	CRF01_AE	1660:1667	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	10	47	theme	PNGS	1500:1503	arg1	presence					1445:1452	presence	1445:1452	presence of more than 4 of net charges	1445:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	47	theme	PNGS	1500:1503	arg1	coexistence					1399:1409	coexistence	1399:1409	coexistence	1399:1409	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	47	theme	PNGS	1500:1503	arg1	lack					1488:1491	lack	1488:1491	lack of the PNGS within V3	1488:1513	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	47	theme	PNGS	1500:1503	arg1	existence					1386:1394	existence	1386:1394	existence	1386:1394	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	3	48	theme	CRF01_AE	683:690	arg1	viruses					692:698	CRF01_AE viruses	683:698	CRF01_AE viruses	683:698	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	9	49	theme	samples	1197:1203	arg1	proportion					1183:1192	a higher proportion	1174:1192	a higher proportion of samples with CD4 cell count less than 200 cells/μl	1174:1246	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	3	50	theme	low	533:535	arg1	counts					546:551	high or low CD4 cell counts	525:551	high or low CD4 cell counts	525:551	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	0	51	theme	N-linked	43:50	arg1	sites					66:70	potential N-linked glycosylation sites	33:70	potential N-linked glycosylation sites	33:70	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	9	52	theme	CD4	1210:1212	arg1	count					1219:1223	CD4 cell count	1210:1223	CD4 cell count less than 200 cells/μl	1210:1246	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	2	53	theme	Compared	355:362	arg1	analysis					364:371	DESIGN Compared analysis	348:371	DESIGN Compared analysis	348:371	DESIGN Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE.
30889014	7	54	theme	amino	989:993	arg1	sequences					1000:1008	amino acid sequences	989:1008	amino acid sequences	989:1008	The properties of amino acid sequences were analyzed by the online ProtParam tool.
30889014	10	55	theme	Shorter	1249:1255	arg1	length					1268:1273	Shorter amino acid length	1249:1273	Shorter amino acid length	1249:1273	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	12	56	theme	amino	1807:1811	arg1	length					1818:1823	amino acid length	1807:1823	specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region	1736:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	4	57	dep	METHODS	701:707	arg1	genotypes					713:721	The genotypes	709:721	METHODS The genotypes of newly identified strains	701:749	METHODS The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06.
30889014	11	58	theme	Northeast	1628:1636	arg1	China					1638:1642	Northeast China	1628:1642	Northeast China	1628:1642	CONCLUSION CRF01_AE has dominated HIV-1 genotype in Northeast China.
30889014	1	59	from	China	341:345	arg1	pathogenesis					263:274	pathogenesis	263:274	pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China	263:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	3	60	theme	cell	541:544	arg1	counts					546:551	high or low CD4 cell counts	525:551	high or low CD4 cell counts	525:551	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	1	61	theme	circulating	279:289	arg1	strains					320:326	circulating recombinant form (CRF) 01_AE strains	279:326	circulating recombinant form (CRF) 01_AE strains in Northeast China	279:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	12	62	theme	amino	1745:1749	arg1	region					1831:1836	V4 region	1828:1836	V4 region	1828:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	62	theme	amino	1745:1749	arg1	residues					1756:1763	specific amino acid residues	1736:1763	specific amino acid residues	1736:1763	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	6	63	theme	glycosylation	884:896	arg1	PNGS					904:907	PNGS	904:907	PNGS	904:907	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	6	63	theme	glycosylation	884:896	arg1	site					898:901	Potential N-linked glycosylation site	865:901	Potential N-linked glycosylation site (PNGS) number	865:915	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	3	64	theme	different	578:586	arg1	usages					599:604	different coreceptor usages	578:604	different coreceptor usages	578:604	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	1	65	theme	form	303:306	arg1	strains					320:326	circulating recombinant form (CRF) 01_AE strains	279:326	circulating recombinant form (CRF) 01_AE strains in Northeast China	279:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	10	66	theme	CD4	1366:1368	arg1	count					1375:1379	a lower CD4 cell count	1358:1379	a lower CD4 cell count	1358:1379	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	67	theme	X4/R5X4	1530:1536	arg1	usage					1549:1553	the X4/R5X4 coreceptor usage	1526:1553	the X4/R5X4 coreceptor usage of CRF01_AE viruses	1526:1573	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	6	68	theme	Potential	865:873	arg1	PNGS					904:907	PNGS	904:907	PNGS	904:907	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	6	68	theme	Potential	865:873	arg1	site					898:901	Potential N-linked glycosylation site	865:901	Potential N-linked glycosylation site (PNGS) number	865:915	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	6	69	theme	N-glycosite	949:959	arg1	software					961:968	the online N-glycosite software	938:968	the online N-glycosite software	938:968	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	8	70	theme	HIV-1	1087:1091	arg1	genotype					1093:1100	the main HIV-1 genotype	1078:1100	the main HIV-1 genotype since 2010	1078:1111	RESULTS CRF01_AE become the main HIV-1 genotype since 2010.
30889014	10	71	from	presence	1296:1303	arg1	V4					1341:1342	V4	1341:1342	V4	1341:1342	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	72	theme	CRF01_AE	1558:1565	arg1	viruses					1567:1573	CRF01_AE viruses	1558:1573	CRF01_AE viruses	1558:1573	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	0	73	theme	Northeast	137:145	arg1	China					147:151	Northeast China	137:151	Northeast China	137:151	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	3	74	with	samples	512:518	arg1	counts					546:551	high or low CD4 cell counts	525:551	high or low CD4 cell counts	525:551	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	3	75	theme	possible	631:638	arg1	factors					640:646	the possible factors	627:646	the possible factors correlating to the pathogenesis of CRF01_AE viruses	627:698	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	1	76	theme	critical	230:237	arg1	factors					239:245	critical factors	230:245	critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China	230:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	6	77	gly	glycosylation	884:896	arg2	site					898:901	Potential N-linked glycosylation site	865:901	Potential N-linked glycosylation site (PNGS) number	865:915	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	6	77	gly	glycosylation	884:896	arg2	PNGS					904:907	PNGS	904:907	PNGS	904:907	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	1	78	from	pathogenesis	263:274	arg1	China					341:345	Northeast China	331:345	Northeast China	331:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	0	79	from	pathogenesis	121:132	arg1	China					147:151	Northeast China	137:151	Northeast China	137:151	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	12	80	theme	disease	1686:1692	arg1	progression					1694:1704	a fast disease progression	1679:1704	a fast disease progression	1679:1704	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	4	81	theme	phylogenetic	770:781	arg1	analyses					783:790	phylogenetic analyses	770:790	phylogenetic analyses using Mega 6.06	770:806	METHODS The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06.
30889014	3	82	theme	high	525:528	arg1	counts					546:551	high or low CD4 cell counts	525:551	high or low CD4 cell counts	525:551	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	5	83	theme	Coreceptor	809:818	arg1	usage					820:824	Coreceptor usage	809:824	Coreceptor usage	809:824	Coreceptor usage was predicted by Geno2Pheno algorithm.
30889014	9	84	dep	cells/μl	1239:1246	arg1	200					1235:1237	200	1235:1237	200	1235:1237	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	10	85	theme	basic	1310:1314	arg1	R/KNXT					1322:1327	a basic motif R/KNXT	1308:1327	a basic motif R/KNXT	1308:1327	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	0	86	theme	circulating	86:96	arg1	pathogenesis					121:132	circulating recombinant form 01_AE pathogenesis	86:132	circulating recombinant form 01_AE pathogenesis in Northeast China	86:151	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	1	87	theme	current	168:174	arg1	study					176:180	The current study	164:180	The current study	164:180	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	4	88	theme	strains	743:749	arg1	genotypes					713:721	The genotypes	709:721	METHODS The genotypes of newly identified strains	701:749	METHODS The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06.
30889014	9	89	theme	non-CRF01_AE	1128:1139	arg1	group					1141:1145	non-CRF01_AE group	1128:1145	non-CRF01_AE group	1128:1145	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	0	90	theme	form	110:113	arg1	pathogenesis					121:132	circulating recombinant form 01_AE pathogenesis	86:132	circulating recombinant form 01_AE pathogenesis in Northeast China	86:151	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	7	91	theme	ProtParam	1038:1046	arg1	tool					1048:1051	the online ProtParam tool	1027:1051	the online ProtParam tool	1027:1051	The properties of amino acid sequences were analyzed by the online ProtParam tool.
30889014	10	92	theme	NR/KT	1332:1336	arg1	length					1268:1273	Shorter amino acid length	1249:1273	Shorter amino acid length	1249:1273	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	92	theme	NR/KT	1332:1336	arg1	PNGSs					1282:1286	fewer PNGSs	1276:1286	fewer PNGSs	1276:1286	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	92	theme	NR/KT	1332:1336	arg1	presence					1296:1303	the presence	1292:1303	the presence of a basic motif R/KNXT or NR/KT in V4	1292:1342	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	12	93	dep	V3	1778:1779	arg1	regions					1788:1794	regions	1788:1794	regions	1788:1794	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	94	from	residues	1756:1763	arg1	V4					1785:1786	V4	1785:1786	V4	1785:1786	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	94	from	residues	1756:1763	arg1	V3					1778:1779	V3	1778:1779	V3	1778:1779	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	9	95	theme	CRF01_AE	1152:1159	arg1	group					1161:1165	the CRF01_AE group	1148:1165	the CRF01_AE group	1148:1165	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	0	96	theme	amino	9:13	arg1	residues					20:27	Critical amino acid residues	0:27	Critical amino acid residues	0:27	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	8	97	dep	CRF01_AE	1062:1069	arg1	become					1071:1076	become	1071:1076	CRF01_AE become the main HIV-1 genotype since 2010	1062:1111	RESULTS CRF01_AE become the main HIV-1 genotype since 2010.
30889014	2	98	theme	non-CRF01_AE	403:414	arg1	samples					416:422	non-CRF01_AE samples	403:422	non-CRF01_AE samples	403:422	DESIGN Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE.
30889014	7	99	theme	sequences	1000:1008	arg1	properties					975:984	The properties	971:984	The properties of amino acid sequences	971:1008	The properties of amino acid sequences were analyzed by the online ProtParam tool.
30889014	2	100	theme	CRF01_AE	468:475	arg1	features					456:463	the pathogenicity features	438:463	the pathogenicity features of CRF01_AE	438:475	DESIGN Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE.
30889014	10	101	theme	charges	1476:1482	arg1	charges					1476:1482	net charges	1472:1482	net charges	1472:1482	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	101	theme	charges	1476:1482	arg1	4					1467:1467	4	1467:1467	4	1467:1467	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	3	102	theme	viruses	692:698	arg1	pathogenesis					667:678	the pathogenesis	663:678	the pathogenesis of CRF01_AE viruses	663:698	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	9	103	theme	higher	1176:1181	arg1	proportion					1183:1192	a higher proportion	1174:1192	a higher proportion of samples with CD4 cell count less than 200 cells/μl	1174:1246	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	3	104	with	samples	565:571	arg1	usages					599:604	different coreceptor usages	578:604	different coreceptor usages	578:604	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	1	105	theme	strains	320:326	arg1	pathogenesis					263:274	pathogenesis	263:274	pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China	263:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	12	106	theme	region	1831:1836	arg1	region					1831:1836	V4 region	1828:1836	V4 region	1828:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	106	theme	region	1831:1836	arg1	PNGSs					1769:1773	PNGSs	1769:1773	PNGSs	1769:1773	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	106	theme	region	1831:1836	arg1	length					1818:1823	amino acid length	1807:1823	specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region	1736:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	12	106	theme	region	1831:1836	arg1	residues					1756:1763	specific amino acid residues	1736:1763	specific amino acid residues	1736:1763	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	9	107	dep	count	1219:1223	arg1	cells/μl					1239:1246	cells/μl	1239:1246	cells/μl	1239:1246	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	10	108	attach	presence	1296:1303	arg1	V4					1341:1342	V4	1341:1342	V4	1341:1342	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	108	attach	presence	1296:1303	arg2	NR/KT					1332:1336	NR/KT	1332:1336	NR/KT	1332:1336	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	108	attach	presence	1296:1303	arg2	R/KNXT					1322:1327	a basic motif R/KNXT	1308:1327	a basic motif R/KNXT	1308:1327	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	109	theme	cell	1370:1373	arg1	count					1375:1379	a lower CD4 cell count	1358:1379	a lower CD4 cell count	1358:1379	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	3	110	theme	CRF01_AE	503:510	arg1	samples					512:518	CRF01_AE samples	503:518	CRF01_AE samples with high or low CD4 cell counts	503:551	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	0	111	theme	glycosylation	52:64	arg1	sites					66:70	potential N-linked glycosylation sites	33:70	potential N-linked glycosylation sites	33:70	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	1	112	theme	Northeast	331:339	arg1	China					341:345	Northeast China	331:345	Northeast China	331:345	OBJECTIVE The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.
30889014	10	113	theme	lower	1360:1364	arg1	count					1375:1379	a lower CD4 cell count	1358:1379	a lower CD4 cell count	1358:1379	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	3	114	theme	CD4	537:539	arg1	counts					546:551	high or low CD4 cell counts	525:551	high or low CD4 cell counts	525:551	Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.
30889014	0	115	gly	glycosylation	52:64	arg2	sites					66:70	potential N-linked glycosylation sites	33:70	potential N-linked glycosylation sites	33:70	Critical amino acid residues and potential N-linked glycosylation sites contribute to circulating recombinant form 01_AE pathogenesis in Northeast China.
30889014	12	116	theme	acid	1813:1816	arg1	length					1818:1823	amino acid length	1807:1823	specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region	1736:1836	Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.
30889014	9	117	theme	cell	1214:1217	arg1	count					1219:1223	CD4 cell count	1210:1223	CD4 cell count less than 200 cells/μl	1210:1246	Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl.
30889014	2	118	theme	DESIGN	348:353	arg1	analysis					364:371	DESIGN Compared analysis	348:371	DESIGN Compared analysis	348:371	DESIGN Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE.
30889014	10	119	theme	R/KNXT	1322:1327	arg1	length					1268:1273	Shorter amino acid length	1249:1273	Shorter amino acid length	1249:1273	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	119	theme	R/KNXT	1322:1327	arg1	PNGSs					1282:1286	fewer PNGSs	1276:1286	fewer PNGSs	1276:1286	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	10	119	theme	R/KNXT	1322:1327	arg1	presence					1296:1303	the presence	1292:1303	the presence of a basic motif R/KNXT or NR/KT in V4	1292:1342	Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.
30889014	6	120	link	N-linked	875:882	arg1	PNGS					904:907	PNGS	904:907	PNGS	904:907	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	6	120	link	N-linked	875:882	arg1	site					898:901	Potential N-linked glycosylation site	865:901	Potential N-linked glycosylation site (PNGS) number	865:915	Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software.
30889014	11	121	theme	CONCLUSION	1576:1585	arg1	CRF01_AE					1587:1594	CONCLUSION CRF01_AE	1576:1594	CONCLUSION CRF01_AE	1576:1594	CONCLUSION CRF01_AE has dominated HIV-1 genotype in Northeast China.
31578522	8	0	theme	genera	1070:1075	arg1	Candida					1077:1083	the genera Candida	1066:1083	the genera Candida	1066:1083	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	4	1	from	tumours	469:475	arg1	models					497:502	humans and mouse models	480:502	humans and mouse models of this	480:510	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	3	2	theme	PDA	460:462	arg1	pathogenesis					444:455	the pathogenesis	440:455	the pathogenesis of PDA	440:462	Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA.
31578522	5	3	dep	gut	686:688	arg1	the					682:684	the	682:684	the	682:684	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	9	4	theme	MBL	1344:1346	arg1	deletion					1332:1339	deletion	1332:1339	deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour	1332:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	10	5	from	progression	1529:1539	arg1	C3-deficient					1580:1591	C3-deficient	1580:1591	C3-deficient	1580:1591	In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice.
31578522	10	5	from	progression	1529:1539	arg1	Mbl-					1551:1554	Mbl-	1551:1554	Mbl-	1551:1554	In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice.
31578522	8	6	theme	progressive	964:974	arg1	models					989:994	slowly progressive and invasive models	957:994	slowly progressive and invasive models of PDA	957:1001	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	10	7	dep	Mbl-	1551:1554	arg1	known					1562:1566	known	1562:1566	known as Mbl2	1562:1574	In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice.
31578522	10	7	dep	Mbl-	1551:1554	arg1	mice					1593:1596	mice	1593:1596	mice	1593:1596	In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice.
31578522	5	8	from	that	674:677	arg1	distinct					660:667	distinct	660:667	distinct	660:667	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	5	8	from	that	674:677	arg1	composition					612:622	The composition	608:622	The composition of the mycobiome of PDA tumours	608:654	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	8	9	from	growth	947:952	arg1	models					989:994	slowly progressive and invasive models	957:994	slowly progressive and invasive models of PDA	957:1001	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	4	10	theme	PDA	465:467	arg1	tumours					469:475	PDA tumours	465:475	PDA tumours in humans and mouse models of this	465:510	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	8	11	theme	mycobiome	907:915	arg1	Ablation					891:898	Ablation	891:898	Ablation of the mycobiome	891:915	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	9	12	dep	protective	1433:1442	arg1	both					1428:1431	both	1428:1431	both	1428:1431	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	10	13	theme	PDA	1544:1546	arg1	progression					1529:1539	the progression	1525:1539	the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice	1525:1596	In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice.
31578522	9	14	theme	C3	1351:1352	arg1	deletion					1332:1339	deletion	1332:1339	deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour	1332:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	6	15	theme	Malassezia	850:859	arg1	spp					861:863	Malassezia spp	850:863	Malassezia spp	850:863	Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp.
31578522	8	16	theme	invasive	980:987	arg1	models					989:994	slowly progressive and invasive models	957:994	slowly progressive and invasive models of PDA	957:1001	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	1	17	dep	colon	147:151	arg1	cancer					163:168	cancer	163:168	cancer	163:168	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	10	18	theme	mycobiome	1501:1509	arg1	reprogramming					1480:1492	reprogramming	1480:1492	reprogramming of the mycobiome	1480:1509	In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice.
31578522	8	19	theme	tumour	940:945	arg1	growth					947:952	tumour growth	940:952	tumour growth in slowly progressive and invasive models of PDA	940:1001	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	8	20	theme	PDA	999:1001	arg1	models					989:994	slowly progressive and invasive models	957:994	slowly progressive and invasive models of PDA	957:1001	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	9	21	theme	C3aR	1402:1405	arg1	knockdown					1389:1397	the extratumoral compartment-or knockdown	1357:1397	the extratumoral compartment-or knockdown of C3aR in tumour	1357:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	4	22	from	increase	532:539	arg1	fungi					544:548	fungi	544:548	fungi of about 3,000-fold compared to normal pancreatic tissue	544:605	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	9	23	theme	fungal	1236:1241	arg1	wall					1243:1246	the fungal wall	1232:1246	the fungal wall	1232:1246	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	11	24	theme	complement	1677:1686	arg1	cascade					1688:1694	the complement cascade	1673:1694	the complement cascade	1673:1694	Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL.
31578522	1	25	theme	Bacterial	76:84	arg1	dysbiosis					86:94	Bacterial dysbiosis	76:94	Bacterial dysbiosis	76:94	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	9	26	theme	extratumoral	1361:1372	arg1	knockdown					1389:1397	the extratumoral compartment-or knockdown	1357:1397	the extratumoral compartment-or knockdown of C3aR in tumour	1357:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	0	27	theme	fungal	4:9	arg1	mycobiome					11:19	The fungal mycobiome	0:19	The fungal mycobiome	0:19	The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.
31578522	9	28	from	deletion	1332:1339	arg1	knockdown					1389:1397	the extratumoral compartment-or knockdown	1357:1397	the extratumoral compartment-or knockdown of C3aR in tumour	1357:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	5	29	theme	normal	693:698	arg1	pancreas					700:707	normal pancreas	693:707	normal pancreas	693:707	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	9	30	theme	wall	1243:1246	arg1	glycans					1221:1227	glycans	1221:1227	glycans of the fungal wall	1221:1246	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	9	31	theme	compartment-or	1374:1387	arg1	knockdown					1389:1397	the extratumoral compartment-or knockdown	1357:1397	the extratumoral compartment-or knockdown of C3aR in tumour	1357:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	5	32	theme	indices	751:757	arg1	basis					716:720	the basis	712:720	the basis of alpha- and beta-diversity indices	712:757	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	4	33	theme	this	507:510	arg1	models					497:502	humans and mouse models	480:502	humans and mouse models of this	480:510	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	9	34	theme	mannose-binding	1176:1190	arg1	MBL					1200:1202	MBL	1200:1202	MBL	1200:1202	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	9	34	theme	mannose-binding	1176:1190	arg1	lectin					1192:1197	mannose-binding lectin	1176:1197	mannose-binding lectin (MBL)	1176:1203	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	4	35	theme	pancreatic	589:598	arg1	tissue					600:605	normal pancreatic tissue	582:605	normal pancreatic tissue	582:605	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	9	36	theme	complement	1264:1273	arg1	cascade					1275:1281	the complement cascade	1260:1281	the complement cascade	1260:1281	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	9	37	theme	lectin	1192:1197	arg1	ligation					1164:1171	ligation	1164:1171	ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade,	1164:1282	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	4	38	theme	normal	582:587	arg1	tissue					600:605	normal pancreatic tissue	582:605	normal pancreatic tissue	582:605	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	6	39	theme	PDA	812:814	arg1	tumours					816:822	the fungal community that infiltrated PDA tumours	774:822	the fungal community that infiltrated PDA tumours	774:822	Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp.
31578522	0	40	theme	pancreatic	30:39	arg1	oncogenesis					41:51	pancreatic oncogenesis	30:51	pancreatic oncogenesis	30:51	The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.
31578522	4	41	theme	humans and	480:489	arg1	models					497:502	humans and mouse models	480:502	humans and mouse models of this	480:510	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	8	42	from	species	1055:1061	arg1	Candida					1077:1083	the genera Candida	1066:1083	the genera Candida	1066:1083	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	6	43	theme	infiltrated	800:810	arg1	tumours					816:822	the fungal community that infiltrated PDA tumours	774:822	the fungal community that infiltrated PDA tumours	774:822	Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp.
31578522	8	44	theme	Aspergillus-accelerated	1103:1125	arg1	species					1055:1061	species	1055:1061	species in the genera Candida	1055:1083	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	8	44	theme	Aspergillus-accelerated	1103:1125	arg1	oncogenesis					1127:1137	Aspergillus-accelerated oncogenesis	1103:1137	Aspergillus-accelerated oncogenesis	1103:1137	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	5	45	theme	alpha-	725:730	arg1	indices					751:757	alpha- and beta-diversity indices	725:757	alpha- and beta-diversity indices	725:757	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	5	46	theme	mycobiome	631:639	arg1	composition					612:622	The composition	608:622	The composition of the mycobiome of PDA tumours	608:654	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	5	46	theme	mycobiome	631:639	arg1	distinct					660:667	distinct	660:667	distinct	660:667	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	6	47	theme	that	795:798	arg1	tumours					816:822	the fungal community that infiltrated PDA tumours	774:822	the fungal community that infiltrated PDA tumours	774:822	Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp.
31578522	9	48	from	tumour	1410:1415	arg1	knockdown					1389:1397	the extratumoral compartment-or knockdown	1357:1397	the extratumoral compartment-or knockdown of C3aR in tumour	1357:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	3	49	theme	gut	382:384	arg1	lumen					386:390	the gut lumen	378:390	the gut lumen	378:390	Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA.
31578522	9	50	theme	oncogenic	1301:1309	arg1	progression					1311:1321	oncogenic progression	1301:1321	oncogenic progression	1301:1321	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	6	51	theme	community	785:793	arg1	tumours					816:822	the fungal community that infiltrated PDA tumours	774:822	the fungal community that infiltrated PDA tumours	774:822	Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp.
31578522	11	52	theme	pathogenic	1633:1642	arg1	fungi					1644:1648	pathogenic fungi	1633:1648	pathogenic fungi	1633:1648	Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL.
31578522	1	53	from	carcinogenesis	108:121	arg1	liver					157:161	liver	157:161	liver	157:161	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	1	53	from	carcinogenesis	108:121	arg1	malignancies					126:137	malignancies	126:137	malignancies such as colon and liver cancer	126:168	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	1	53	from	carcinogenesis	108:121	arg1	colon					147:151	colon	147:151	colon	147:151	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	4	54	theme	mouse	491:495	arg1	models					497:502	humans and mouse models	480:502	humans and mouse models of this	480:510	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	5	55	theme	PDA	644:646	arg1	tumours					648:654	PDA tumours	644:654	PDA tumours	644:654	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	6	56	theme	fungal	778:783	arg1	tumours					816:822	the fungal community that infiltrated PDA tumours	774:822	the fungal community that infiltrated PDA tumours	774:822	Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp.
31578522	10	57	dep	known	1562:1566	arg1	also					1557:1560	also	1557:1560	also	1557:1560	In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice.
31578522	4	58	theme	3,000-fold	559:568	arg1	fungi					544:548	fungi	544:548	fungi of about 3,000-fold compared to normal pancreatic tissue	544:605	PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue.
31578522	5	59	theme	tumours	648:654	arg1	mycobiome					631:639	the mycobiome	627:639	the mycobiome of PDA tumours	627:654	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	11	60	theme	MBL	1722:1724	arg1	activation					1708:1717	the activation	1704:1717	the activation of MBL	1704:1724	Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL.
31578522	1	61	theme	pancreatic	227:236	arg1	PDA					261:263	PDA	261:263	PDA	261:263	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	1	61	theme	pancreatic	227:236	arg1	adenocarcinoma					245:258	pancreatic ductal adenocarcinoma (PDA)1	227:265	pancreatic ductal adenocarcinoma (PDA)1	227:265	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	0	62	theme	MBL	71:73	arg1	activation					57:66	activation	57:66	activation of MBL	57:73	The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.
31578522	9	63	from	knockdown	1389:1397	arg1	tumour					1410:1415	tumour	1410:1415	tumour	1410:1415	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	9	64	theme	tumour	1452:1457	arg1	growth					1459:1464	tumour growth	1452:1464	tumour growth	1452:1464	We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth.
31578522	8	65	with	repopulation	1008:1019	arg1	Malassezia					1028:1037	a Malassezia	1026:1037	a Malassezia	1026:1037	Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis.
31578522	1	66	theme	ductal	238:243	arg1	PDA					261:263	PDA	261:263	PDA	261:263	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	1	66	theme	ductal	238:243	arg1	adenocarcinoma					245:258	pancreatic ductal adenocarcinoma (PDA)1	227:265	pancreatic ductal adenocarcinoma (PDA)1	227:265	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
31578522	5	67	theme	beta-diversity	736:749	arg1	indices					751:757	alpha- and beta-diversity indices	725:757	alpha- and beta-diversity indices	725:757	The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices.
31578522	1	68	theme	adenocarcinoma	245:258	arg1	pathogenesis					211:222	the pathogenesis	207:222	the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1	207:265	Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1.
29385603	2	0	dep	parity	517:522	arg1	to					526:527	to	526:527	to	526:527	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	14	1	theme	feed	2483:2486	arg1	intake					2488:2493	sow feed intake	2479:2493	sow feed intake	2479:2493	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	9	2	theme	litter	1526:1531	arg1	size					1533:1536	litter size	1526:1536	litter size	1526:1536	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	8	3	theme	xylanase	1335:1342	arg1	Supplementation					1316:1330	Supplementation	1316:1330	Supplementation of xylanase	1316:1342	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	3	4	from	mating	588:593	arg1	diet					578:581	a standard gestation diet	557:581	a standard gestation diet from mating	557:593	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	1	5	theme	coarsely	252:259	arg1	diet					278:281	a coarsely ground lactation diet	250:281	a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%)	250:340	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	7	6	theme	sows	1159:1162	arg1	yield					1188:1192	yield	1188:1192	yield	1188:1192	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	6	theme	sows	1159:1162	arg1	growth					1165:1170	growth	1165:1170	growth of the piglets	1165:1185	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	6	theme	sows	1159:1162	arg1	performance					1140:1150	Reproductive performance	1127:1150	Reproductive performance of the sows	1127:1162	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	6	theme	sows	1159:1162	arg1	composition					1198:1208	composition	1198:1208	composition	1198:1208	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	4	7	theme	mono-component	863:876	arg1	xylanase					878:885	a mono-component xylanase	861:885	a mono-component xylanase dosed at 200 enzyme unit (FXU)	861:916	The enzyme applied was a mono-component xylanase dosed at 200 enzyme unit (FXU) per kg of feed, which corresponds to 200 g per ton of feed.
29385603	4	7	theme	mono-component	863:876	arg1	enzyme					842:847	The enzyme	838:847	The enzyme applied	838:855	The enzyme applied was a mono-component xylanase dosed at 200 enzyme unit (FXU) per kg of feed, which corresponds to 200 g per ton of feed.
29385603	14	8	theme	mono-component	2369:2382	arg1	xylanase					2384:2391	a mono-component xylanase	2367:2391	a mono-component xylanase	2367:2391	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	1	9	theme	lactation	268:276	arg1	diet					278:281	a coarsely ground lactation diet	250:281	a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%)	250:340	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	7	10	theme	piglets	1179:1185	arg1	yield					1188:1192	yield	1188:1192	yield	1188:1192	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	10	theme	piglets	1179:1185	arg1	growth					1165:1170	growth	1165:1170	growth of the piglets	1165:1185	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	10	theme	piglets	1179:1185	arg1	performance					1140:1150	Reproductive performance	1127:1150	Reproductive performance of the sows	1127:1162	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	10	theme	piglets	1179:1185	arg1	composition					1198:1208	composition	1198:1208	composition	1198:1208	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	3	11	theme	enzyme	824:829	arg1	diet					831:834	supplemented enzyme (enzyme diet)	803:835	supplemented enzyme (enzyme diet)	803:835	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	12	12	theme	P	1948:1948	arg1	<					1950:1950	P < 0.01	1948:1955	P < 0.01	1948:1955	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	3	13	theme	gestation	612:620	arg1	day					601:603	day 108	601:607	day 108 of gestation	601:620	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	9	14	dep	BW	1499:1500	arg1	thickness					1515:1523	fat thickness	1511:1523	fat thickness	1511:1523	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	8	15	theme	born	1392:1395	arg1	piglets					1397:1403	total born and live born piglets	1372:1403	total born and live born piglets	1372:1403	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	12	16	theme	nonstarch	2057:2065	arg1	polysaccharides					2067:2081	total nonstarch polysaccharides	2051:2081	total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02)	2051:2112	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	7	17	theme	Reproductive	1127:1138	arg1	performance					1140:1150	Reproductive performance	1127:1150	Reproductive performance of the sows	1127:1162	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	13	18	dep	affected	2211:2218	arg1	>					2223:2223	P > 0.05	2221:2228	P > 0.05	2221:2228	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
29385603	1	19	theme	lactating	428:436	arg1	sows					438:441	lactating sows	428:441	lactating sows	428:441	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	12	20	theme	P	2037:2037	arg1	<					2039:2039	P < 0.01	2037:2044	P < 0.01	2037:2044	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	20	theme	P	2037:2037	arg1	OM					2018:2019	OM	2018:2019	OM (86.5 vs. 85.7, P < 0.01)	2018:2045	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	4	21	theme	unit	907:910	arg1	FXU					913:915	200 enzyme unit (FXU)	896:916	200 enzyme unit (FXU)	896:916	The enzyme applied was a mono-component xylanase dosed at 200 enzyme unit (FXU) per kg of feed, which corresponds to 200 g per ton of feed.
29385603	0	22	theme	ground	126:131	arg1	diet					133:136	a coarsely ground diet	115:136	a coarsely ground diet	115:136	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	2	23	theme	×	486:486	arg1	Yorkshire					488:496	Danish Landrace × Yorkshire	470:496	Danish Landrace × Yorkshire	470:496	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	9	24	theme	Initial	1444:1450	arg1	weight					1565:1570	litter weight	1558:1570	litter weight	1558:1570	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	9	24	theme	Initial	1444:1450	arg1	BW					1499:1500	sow BW	1495:1500	sow BW	1495:1500	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	9	24	theme	Initial	1444:1450	arg1	size					1533:1536	litter size	1526:1536	litter size	1526:1536	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	9	24	theme	Initial	1444:1450	arg1	weight					1546:1551	piglet weight	1539:1551	piglet weight	1539:1551	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	9	24	theme	Initial	1444:1450	arg1	parameters					1452:1461	Initial parameters	1444:1461	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight	1444:1570	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	14	25	theme	piglet	2597:2602	arg1	performance					2604:2614	piglet performance	2597:2614	piglet performance	2597:2614	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	9	26	theme	P	1586:1586	arg1	>					1588:1588	P > 0.05	1586:1593	P > 0.05	1586:1593	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	14	27	theme	nutrient	2499:2506	arg1	digestibility					2508:2520	nutrient digestibility	2499:2520	nutrient digestibility	2499:2520	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	3	28	theme	dietary	712:718	arg1	treatments					720:729	two dietary treatments	708:729	two dietary treatments (n = 15 per treatment)	708:752	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	3	28	theme	dietary	712:718	arg1	diet					767:770	a lactation diet	755:770	a lactation diet without (control diet)	755:793	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	2	29	theme	sows	511:514	arg1	total					446:450	A total	444:450	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5)	444:530	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	5	30	theme	lactation	1024:1032	arg1	day					1014:1016	day 28	1014:1019	day 28 of lactation	1014:1032	The diets were fed until weaning at day 28 of lactation.
29385603	13	31	theme	Milk	2162:2165	arg1	composition					2167:2177	Milk composition	2162:2177	Milk composition	2162:2177	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
29385603	1	32	theme	soybean	370:376	arg1	meal					378:381	wheat, barley, and soybean meal	351:381	wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows	351:441	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	7	33	theme	nutrients	1291:1299	arg1	yield					1188:1192	yield	1188:1192	yield	1188:1192	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	33	theme	nutrients	1291:1299	arg1	growth					1165:1170	growth	1165:1170	growth of the piglets	1165:1185	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	33	theme	nutrients	1291:1299	arg1	performance					1140:1150	Reproductive performance	1127:1150	Reproductive performance of the sows	1127:1162	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	33	theme	nutrients	1291:1299	arg1	composition					1198:1208	composition	1198:1208	composition	1198:1208	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	10	34	theme	daily	1673:1677	arg1	yield					1684:1688	daily milk yield	1673:1688	daily milk yield	1673:1688	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	3	35	theme	average	667:673	arg1	BW					647:648	BW	647:648	BW (295.4 ± 26.1 kg average BW)	647:677	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	3	35	theme	average	667:673	arg1	BW					675:676	295.4 ± 26.1 kg average BW	651:676	295.4 ± 26.1 kg average BW	651:676	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	1	36	from	meal	378:381	arg1	digestibility					395:407	nutrient digestibility	386:407	nutrient digestibility	386:407	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	1	36	from	meal	378:381	arg1	performance					413:423	performance	413:423	performance	413:423	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	14	37	theme	sow	2479:2481	arg1	intake					2488:2493	sow feed intake	2479:2493	sow feed intake	2479:2493	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	3	38	theme	=	734:734	arg1	n					732:732	n = 15	732:737	n = 15 per treatment	732:751	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	12	39	dep	84.2	1963:1966	arg1	P					1978:1978	P < 0.01	1978:1985	P < 0.01	1978:1985	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	1	40	theme	current	160:166	arg1	study					168:172	the current study	156:172	the current study	156:172	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	2	41	theme	Danish	470:475	arg1	Yorkshire					488:496	Danish Landrace × Yorkshire	470:496	Danish Landrace × Yorkshire	470:496	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	0	42	from	Effects	0:6	arg1	performance					81:91	performance	81:91	performance	81:91	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	0	42	from	Effects	0:6	arg1	digestibility					63:75	nutrient digestibility	54:75	nutrient digestibility	54:75	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	12	43	dep	<	2039:2039	arg1	85.7					2031:2034	85.7	2031:2034	85.7	2031:2034	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	43	dep	<	2039:2039	arg1	86.5					2022:2025	86.5	2022:2025	86.5	2022:2025	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	11	44	theme	xylanase	1868:1875	arg1	addition					1877:1884	xylanase addition	1868:1884	xylanase addition	1868:1884	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	10	45	theme	weight	1643:1648	arg1	gain					1650:1653	litter weight gain	1636:1653	litter weight gain	1636:1653	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	0	46	theme	sows	106:109	arg1	performance					81:91	performance	81:91	performance	81:91	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	0	46	theme	sows	106:109	arg1	digestibility					63:75	nutrient digestibility	54:75	nutrient digestibility	54:75	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	7	47	theme	tract	1261:1265	arg1	digestibility					1267:1279	apparent total tract digestibility	1246:1279	apparent total tract digestibility (ATTD)	1246:1286	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	47	theme	tract	1261:1265	arg1	ATTD					1282:1285	ATTD	1282:1285	ATTD	1282:1285	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	2	48	theme	cross-bred	458:467	arg1	sows					511:514	30 cross-bred (Danish Landrace × Yorkshire) multiparous sows	455:514	30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5)	455:530	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	2	48	theme	cross-bred	458:467	arg1	parity					517:522	parity 2 to 5	517:529	parity 2 to 5	517:529	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	10	49	theme	P	1706:1706	arg1	>					1708:1708	P > 0.05	1706:1713	P > 0.05	1706:1713	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	13	50	theme	xylanase	2290:2297	arg1	addition					2299:2306	xylanase addition	2290:2306	xylanase addition	2290:2306	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
29385603	12	51	theme	<	1980:1980	arg1	P					1978:1978	P < 0.01	1978:1985	P < 0.01	1978:1985	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	9	52	from	parameters	1452:1461	arg1	day					1466:1468	day 2	1466:1470	day 2 of lactation	1466:1483	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	0	53	theme	mono-component	11:24	arg1	supplementation					35:49	mono-component xylanase supplementation	11:49	mono-component xylanase supplementation	11:49	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	1	54	theme	feed	284:287	arg1	size					307:310	feed fraction particle size	284:310	feed fraction particle size above 2 mm	284:321	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	9	55	theme	lactation	1475:1483	arg1	day					1466:1468	day 2	1466:1470	day 2 of lactation	1466:1483	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	12	56	theme	GE	1929:1930	arg1	83.4					1972:1975	83.4	1972:1975	83.4	1972:1975	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	N					1989:1989	N	1989:1989	N (83.4 vs. 81.7, P = 0.02)	1989:2015	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	83.4					1992:1995	83.4	1992:1995	83.4	1992:1995	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	DM					1959:1960	DM	1959:1960	DM (84.2 vs. 83.4, P < 0.01)	1959:1986	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	ATTD					1921:1924	The ATTD	1917:1924	The ATTD of GE (83.9 vs. 82.9, P < 0.01)	1917:1956	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	84.2					1963:1966	84.2	1963:1966	84.2	1963:1966	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	OM					2018:2019	OM	2018:2019	OM (86.5 vs. 85.7, P < 0.01)	2018:2045	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	81.7					2001:2004	81.7	2001:2004	81.7	2001:2004	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	<					2039:2039	P < 0.01	2037:2044	P < 0.01	2037:2044	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	56	theme	GE	1929:1930	arg1	polysaccharides					2067:2081	total nonstarch polysaccharides	2051:2081	total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02)	2051:2112	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	3	57	theme	standard	559:566	arg1	diet					578:581	a standard gestation diet	557:581	a standard gestation diet from mating	557:593	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	0	58	theme	supplementation	35:49	arg1	Effects					0:6	Effects	0:6	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows	0:109	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	1	59	theme	particle	298:305	arg1	size					307:310	feed fraction particle size	284:310	feed fraction particle size above 2 mm	284:321	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	7	60	theme	plasma	1223:1228	arg1	metabolites					1230:1240	plasma metabolites	1223:1240	plasma metabolites	1223:1240	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	10	61	theme	weight	1623:1628	arg1	gain					1630:1633	Piglet weight gain	1616:1633	Piglet weight gain	1616:1633	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	9	62	theme	sow	1495:1497	arg1	BW					1499:1500	sow BW	1495:1500	sow BW	1495:1500	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	12	63	theme	xylanase	2136:2143	arg1	supplementation					2145:2159	xylanase supplementation	2136:2159	xylanase supplementation	2136:2159	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	0	64	theme	nutrient	54:61	arg1	digestibility					63:75	nutrient digestibility	54:75	nutrient digestibility	54:75	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	7	65	theme	milk	1217:1220	arg1	yield					1188:1192	yield	1188:1192	yield	1188:1192	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	65	theme	milk	1217:1220	arg1	growth					1165:1170	growth	1165:1170	growth of the piglets	1165:1185	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	65	theme	milk	1217:1220	arg1	performance					1140:1150	Reproductive performance	1127:1150	Reproductive performance of the sows	1127:1162	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	65	theme	milk	1217:1220	arg1	composition					1198:1208	composition	1198:1208	composition	1198:1208	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	8	66	from	rate	1419:1422	arg1	piglets					1397:1403	total born and live born piglets	1372:1403	total born and live born piglets	1372:1403	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	11	67	theme	=	1855:1855	arg1	P					1853:1853	P = 0.04	1853:1860	P = 0.04	1853:1860	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	11	67	theme	=	1855:1855	arg1	kg					1849:1850	-13.6 to -5.2 kg	1835:1850	-13.6 to -5.2 kg (P = 0.04)	1835:1861	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	3	68	theme	supplemented	803:814	arg1	diet					831:834	supplemented enzyme (enzyme diet)	803:835	supplemented enzyme (enzyme diet)	803:835	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	9	69	theme	fat	1511:1513	arg1	thickness					1515:1523	fat thickness	1511:1523	fat thickness	1511:1523	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	11	70	theme	BW	1783:1784	arg1	loss					1786:1789	BW loss	1783:1789	BW loss during the whole lactation	1783:1816	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	8	71	theme	P	1359:1359	arg1	effect					1351:1356	no effect	1348:1356	no effect (P > 0.05) on total born and live born piglets	1348:1403	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	8	71	theme	P	1359:1359	arg1	>					1361:1361	P > 0.05	1359:1366	P > 0.05	1359:1366	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	12	72	dep	83.4	1992:1995	arg1	P					2007:2007	P = 0.02	2007:2014	P = 0.02	2007:2014	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	13	73	theme	plasma	2244:2249	arg1	triglycerides					2251:2263	plasma triglycerides	2244:2263	plasma triglycerides content	2244:2271	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
29385603	10	74	theme	milk	1679:1682	arg1	yield					1684:1688	daily milk yield	1673:1688	daily milk yield	1673:1688	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	1	75	theme	nutrient	386:393	arg1	digestibility					395:407	nutrient digestibility	386:407	nutrient digestibility	386:407	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	1	76	theme	ground	261:266	arg1	diet					278:281	a coarsely ground lactation diet	250:281	a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%)	250:340	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	9	77	theme	piglet	1539:1544	arg1	weight					1546:1551	piglet weight	1539:1551	piglet weight	1539:1551	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	11	78	dep	-5.2	1844:1847	arg1	to					1841:1842	to	1841:1842	to	1841:1842	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	8	79	theme	born	1378:1381	arg1	piglets					1397:1403	total born and live born piglets	1372:1403	total born and live born piglets	1372:1403	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	1	80	theme	study	168:172	arg1	objective					143:151	The objective	139:151	The objective of the current study	139:172	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	12	81	dep	polysaccharides	2067:2081	arg1	=					2106:2106	=	2106:2106	=	2106:2106	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	13	82	theme	plasma	2183:2188	arg1	metabolites					2190:2200	plasma metabolites	2183:2200	plasma metabolites	2183:2200	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
29385603	13	83	theme	triglycerides	2251:2263	arg1	content					2265:2271	plasma triglycerides content	2244:2271	plasma triglycerides content	2244:2271	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
29385603	4	84	theme	feed	928:931	arg1	kg					922:923	kg	922:923	kg	922:923	The enzyme applied was a mono-component xylanase dosed at 200 enzyme unit (FXU) per kg of feed, which corresponds to 200 g per ton of feed.
29385603	12	85	dep	=	2106:2106	arg1	NSP					2084:2086	NSP	2084:2086	NSP	2084:2086	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	12	86	theme	total	2051:2055	arg1	polysaccharides					2067:2081	total nonstarch polysaccharides	2051:2081	total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02)	2051:2112	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	13	87	theme	P	2221:2221	arg1	>					2223:2223	P > 0.05	2221:2228	P > 0.05	2221:2228	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
29385603	9	88	theme	litter	1558:1563	arg1	weight					1565:1570	litter weight	1558:1570	litter weight	1558:1570	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	2	89	used	used	537:540	arg2	total					446:450	A total	444:450	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5)	444:530	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	1	90	theme	sows	438:441	arg1	digestibility					395:407	nutrient digestibility	386:407	nutrient digestibility	386:407	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	1	90	theme	sows	438:441	arg1	performance					413:423	performance	413:423	performance	413:423	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	11	91	theme	whole	1802:1806	arg1	lactation					1808:1816	the whole lactation	1798:1816	the whole lactation	1798:1816	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	6	92	theme	litter	1058:1063	arg1	size					1065:1068	litter size	1058:1068	litter size of each sow	1058:1080	On day 2 of lactation, litter size of each sow was adjusted to 14 piglets within treatment.
29385603	1	93	theme	wheat	351:355	arg1	meal					378:381	wheat, barley, and soybean meal	351:381	wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows	351:441	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	8	94	theme	stillbirth	1408:1417	arg1	%					1425:1425	%	1425:1425	%	1425:1425	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	8	94	theme	stillbirth	1408:1417	arg1	rate					1419:1422	stillbirth rate	1408:1422	stillbirth rate (%)	1408:1426	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	2	95	theme	Landrace	477:484	arg1	Yorkshire					488:496	Danish Landrace × Yorkshire	470:496	Danish Landrace × Yorkshire	470:496	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	6	96	theme	lactation	1047:1055	arg1	day					1038:1040	day 2	1038:1042	day 2 of lactation	1038:1055	On day 2 of lactation, litter size of each sow was adjusted to 14 piglets within treatment.
29385603	1	97	theme	barley	358:363	arg1	meal					378:381	wheat, barley, and soybean meal	351:381	wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows	351:441	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	11	98	theme	control	1903:1909	arg1	sows					1911:1914	control sows	1903:1914	control sows	1903:1914	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	12	99	dep	83.9	1933:1936	arg1	<					1950:1950	P < 0.01	1948:1955	P < 0.01	1948:1955	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	3	100	theme	treatments	720:729	arg1	treatments					720:729	two dietary treatments	708:729	two dietary treatments (n = 15 per treatment)	708:752	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	3	100	theme	treatments	720:729	arg1	diet					767:770	a lactation diet	755:770	a lactation diet without (control diet)	755:793	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	3	100	theme	treatments	720:729	arg1	one					701:703	one	701:703	one	701:703	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	2	101	theme	multiparous	499:509	arg1	sows					511:514	30 cross-bred (Danish Landrace × Yorkshire) multiparous sows	455:514	30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5)	455:530	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	2	101	theme	multiparous	499:509	arg1	parity					517:522	parity 2 to 5	517:529	parity 2 to 5	517:529	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	14	102	theme	milk	2582:2585	arg1	yield					2587:2591	milk yield	2582:2591	milk yield	2582:2591	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	9	103	dep	similar	1577:1583	arg1	>					1588:1588	P > 0.05	1586:1593	P > 0.05	1586:1593	Initial parameters on day 2 of lactation including sow BW and back fat thickness, litter size, piglet weight, and litter weight were similar (P > 0.05) between treatments.
29385603	11	104	theme	<	1770:1770	arg1	P					1768:1768	P < 0.01	1768:1775	P < 0.01	1768:1775	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	11	104	theme	<	1770:1770	arg1	%					1765:1765	4.5%	1762:1765	4.5% (P < 0.01)	1762:1776	The ADFI was increased by 4.5% (P < 0.01), and BW loss during the whole lactation was reduced from -13.6 to -5.2 kg (P = 0.04) with xylanase addition when compared to control sows.
29385603	12	105	theme	=	2009:2009	arg1	P					2007:2007	P = 0.02	2007:2014	P = 0.02	2007:2014	The ATTD of GE (83.9 vs. 82.9, P < 0.01), DM (84.2 vs. 83.4, P < 0.01), N (83.4 vs. 81.7, P = 0.02), OM (86.5 vs. 85.7, P < 0.01) and total nonstarch polysaccharides (NSP; 59.4 vs. 56.7, P = 0.02) were all increased by xylanase supplementation.
29385603	10	106	theme	Piglet	1616:1621	arg1	gain					1630:1633	Piglet weight gain	1616:1633	Piglet weight gain	1616:1633	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	0	107	theme	lactating	96:104	arg1	sows					106:109	lactating sows	96:109	lactating sows	96:109	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	7	108	theme	digestibility	1267:1279	arg1	yield					1188:1192	yield	1188:1192	yield	1188:1192	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	108	theme	digestibility	1267:1279	arg1	growth					1165:1170	growth	1165:1170	growth of the piglets	1165:1185	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	108	theme	digestibility	1267:1279	arg1	performance					1140:1150	Reproductive performance	1127:1150	Reproductive performance of the sows	1127:1162	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	108	theme	digestibility	1267:1279	arg1	composition					1198:1208	composition	1198:1208	composition	1198:1208	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	1	109	dep	diet	278:281	arg1	%					339:339	more than 17%	327:339	more than 17%	327:339	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	8	110	contain	had	1344:1346	arg2	rate					1419:1422	stillbirth rate	1408:1422	stillbirth rate (%)	1408:1426	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	8	110	contain	had	1344:1346	arg2	effect					1351:1356	no effect	1348:1356	no effect (P > 0.05) on total born and live born piglets	1348:1403	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	8	110	contain	had	1344:1346	arg1	Supplementation					1316:1330	Supplementation	1316:1330	Supplementation of xylanase	1316:1342	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	8	110	contain	had	1344:1346	arg2	>					1361:1361	P > 0.05	1359:1366	P > 0.05	1359:1366	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	8	110	contain	had	1344:1346	arg2	%					1425:1425	%	1425:1425	%	1425:1425	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	14	111	theme	soybean	2457:2463	arg1	meal					2465:2468	soybean meal	2457:2468	soybean meal	2457:2468	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	7	112	theme	total	1255:1259	arg1	digestibility					1267:1279	apparent total tract digestibility	1246:1279	apparent total tract digestibility (ATTD)	1246:1286	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	112	theme	total	1255:1259	arg1	ATTD					1282:1285	ATTD	1282:1285	ATTD	1282:1285	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	10	113	dep	differ	1698:1703	arg1	>					1708:1708	P > 0.05	1706:1713	P > 0.05	1706:1713	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	14	114	theme	BW	2544:2545	arg1	loss					2547:2550	sow BW loss	2540:2550	sow BW loss	2540:2550	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	10	115	theme	litter	1636:1641	arg1	gain					1650:1653	litter weight gain	1636:1653	litter weight gain	1636:1653	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	6	116	theme	sow	1078:1080	arg1	size					1065:1068	litter size	1058:1068	litter size of each sow	1058:1080	On day 2 of lactation, litter size of each sow was adjusted to 14 piglets within treatment.
29385603	3	117	dep	treatments	720:729	arg1	n					732:732	n = 15	732:737	n = 15 per treatment	732:751	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	4	118	theme	enzyme	900:905	arg1	FXU					913:915	200 enzyme unit (FXU)	896:916	200 enzyme unit (FXU)	896:916	The enzyme applied was a mono-component xylanase dosed at 200 enzyme unit (FXU) per kg of feed, which corresponds to 200 g per ton of feed.
29385603	4	119	theme	feed	972:975	arg1	ton					965:967	ton	965:967	ton of feed	965:975	The enzyme applied was a mono-component xylanase dosed at 200 enzyme unit (FXU) per kg of feed, which corresponds to 200 g per ton of feed.
29385603	8	120	from	effect	1351:1356	arg1	piglets					1397:1403	total born and live born piglets	1372:1403	total born and live born piglets	1372:1403	Supplementation of xylanase had no effect (P > 0.05) on total born and live born piglets or stillbirth rate (%) at parturition.
29385603	0	121	theme	coarsely	117:124	arg1	diet					133:136	a coarsely ground diet	115:136	a coarsely ground diet	115:136	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	14	122	theme	sow	2540:2542	arg1	loss					2547:2550	sow BW loss	2540:2550	sow BW loss	2540:2550	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	0	123	theme	xylanase	26:33	arg1	supplementation					35:49	mono-component xylanase supplementation	11:49	mono-component xylanase supplementation	11:49	Effects of mono-component xylanase supplementation on nutrient digestibility and performance of lactating sows fed a coarsely ground diet.
29385603	2	124	dep	cross-bred	458:467	arg1	Yorkshire					488:496	Danish Landrace × Yorkshire	470:496	Danish Landrace × Yorkshire	470:496	A total of 30 cross-bred (Danish Landrace × Yorkshire) multiparous sows (parity 2 to 5) were used.
29385603	1	125	theme	fraction	289:296	arg1	size					307:310	feed fraction particle size	284:310	feed fraction particle size above 2 mm	284:321	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	14	126	theme	ground	2407:2412	arg1	diet					2424:2427	a coarsely ground lactating diet	2396:2427	a coarsely ground lactating diet based on wheat, barley, and soybean meal	2396:2468	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	7	127	theme	apparent	1246:1253	arg1	digestibility					1267:1279	apparent total tract digestibility	1246:1279	apparent total tract digestibility (ATTD)	1246:1286	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	127	theme	apparent	1246:1253	arg1	ATTD					1282:1285	ATTD	1282:1285	ATTD	1282:1285	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	3	128	theme	lactation	757:765	arg1	treatments					720:729	two dietary treatments	708:729	two dietary treatments (n = 15 per treatment)	708:752	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	3	128	theme	lactation	757:765	arg1	diet					767:770	a lactation diet	755:770	a lactation diet without (control diet)	755:793	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	7	129	theme	metabolites	1230:1240	arg1	yield					1188:1192	yield	1188:1192	yield	1188:1192	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	129	theme	metabolites	1230:1240	arg1	growth					1165:1170	growth	1165:1170	growth of the piglets	1165:1185	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	129	theme	metabolites	1230:1240	arg1	performance					1140:1150	Reproductive performance	1127:1150	Reproductive performance of the sows	1127:1162	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	7	129	theme	metabolites	1230:1240	arg1	composition					1198:1208	composition	1198:1208	composition	1198:1208	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	14	130	dep	improved	2470:2477	arg1	whereas					2574:2580	whereas	2574:2580	whereas	2574:2580	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	3	131	theme	control	781:787	arg1	diet					789:792	control diet	781:792	control diet	781:792	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	3	132	theme	gestation	568:576	arg1	diet					578:581	a standard gestation diet	557:581	a standard gestation diet from mating	557:593	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	14	133	theme	lactating	2414:2422	arg1	diet					2424:2427	a coarsely ground lactating diet	2396:2427	a coarsely ground lactating diet based on wheat, barley, and soybean meal	2396:2468	In conclusion, supplementing a mono-component xylanase to a coarsely ground lactating diet based on wheat, barley, and soybean meal improved sow feed intake and nutrient digestibility, thereby reducing sow BW loss throughout lactation, whereas milk yield and piglet performance were not affected.
29385603	1	134	theme	mono-component	223:236	arg1	xylanase					238:245	a mono-component xylanase	221:245	a mono-component xylanase	221:245	The objective of the current study was to investigate the effect of supplementing a mono-component xylanase to a coarsely ground lactation diet (feed fraction particle size above 2 mm was more than 17%) based on wheat, barley, and soybean meal on nutrient digestibility and performance of lactating sows.
29385603	7	135	theme	sow	1213:1215	arg1	milk					1217:1220	sow milk	1213:1220	sow milk	1213:1220	Reproductive performance of the sows, growth of the piglets, yield and composition of sow milk, plasma metabolites and apparent total tract digestibility (ATTD) of nutrients were measured.
29385603	3	136	theme	enzyme	816:821	arg1	diet					831:834	supplemented enzyme (enzyme diet)	803:835	supplemented enzyme (enzyme diet)	803:835	Sows were fed a standard gestation diet from mating until day 108 of gestation, and then stratified for BW (295.4 ± 26.1 kg average BW) and parity to receive one of two dietary treatments (n = 15 per treatment), a lactation diet without (control diet) or with supplemented enzyme (enzyme diet).
29385603	10	137	theme	litter	1656:1661	arg1	size					1663:1666	litter size	1656:1666	litter size	1656:1666	Piglet weight gain, litter weight gain, litter size, and daily milk yield did not differ (P > 0.05) between treatments.
29385603	13	138	dep	=	2329:2329	arg1	mM					2323:2324	0.23 vs. 0.20 mM	2309:2324	0.23 vs. 0.20 mM	2309:2324	Milk composition and plasma metabolites were not affected (P > 0.05), except that plasma triglycerides content was increased by xylanase addition (0.23 vs. 0.20 mM, P = 0.04).
31320997	6	0	theme	AHNAK	903:907	arg1	involvement					888:898	the involvement	884:898	the involvement of AHNAK in the observed paucimannose-dependent effects	884:954	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	4	1	theme	glioblastoma	568:579	arg1	cells					581:585	U-87MG and U-138MG glioblastoma cells	549:585	U-87MG and U-138MG glioblastoma cells	549:585	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	5	2	theme	cell	692:695	arg1	proliferation					697:709	cell proliferation	692:709	cell proliferation	692:709	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	1	3	theme	Glioblastoma	88:99	arg1	multiforme					101:110	Glioblastoma multiforme	88:110	Glioblastoma multiforme	88:110	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	1	3	theme	Glioblastoma	88:99	arg1	type					136:139	an aggressive cancer type	115:139	an aggressive cancer type with poor patient outcomes	115:166	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	7	4	dep	in	1094:1095	arg1	vivo					1097:1100	vivo	1097:1100	vivo	1097:1100	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	3	5	theme	restricted	395:404	arg1	expression					421:430	a very restricted tumor-specific expression	388:430	a very restricted tumor-specific expression	388:430	Paucimannose has only recently been detected in vertebrates where it exhibits a very restricted tumor-specific expression.
31320997	4	6	theme	IV	529:530	arg1	glioblastoma					532:543	human grade IV glioblastoma	517:543	human grade IV glioblastoma	517:543	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	7	7	theme	fatal	1180:1184	arg1	disease					1186:1192	this often fatal disease	1169:1192	this often fatal disease	1169:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	4	8	theme	first	464:468	arg1	time					470:473	the first time	460:473	the first time	460:473	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	7	9	contain	have	1114:1117	arg1	glioblastoma					1047:1058	glioblastoma	1047:1058	glioblastoma	1047:1058	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	7	9	contain	have	1114:1117	arg1	relationship					1063:1074	a relationship	1061:1074	a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease	1061:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	7	9	contain	have	1114:1117	arg2	benefits					1132:1139	far reaching benefits	1119:1139	far reaching benefits	1119:1139	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	6	10	from	involvement	888:898	arg1	effects					948:954	the observed paucimannose-dependent effects	912:954	the observed paucimannose-dependent effects	912:954	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	3	11	theme	tumor-specific	406:419	arg1	expression					421:430	a very restricted tumor-specific expression	388:430	a very restricted tumor-specific expression	388:430	Paucimannose has only recently been detected in vertebrates where it exhibits a very restricted tumor-specific expression.
31320997	4	12	theme	U-87MG	549:554	arg1	cells					581:585	U-87MG and U-138MG glioblastoma cells	549:585	U-87MG and U-138MG glioblastoma cells	549:585	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	5	13	theme	paucimannosidic	632:646	arg1	epitopes					648:655	paucimannosidic epitopes	632:655	paucimannosidic epitopes	632:655	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	0	14	theme	Paucimannosidic	0:14	arg1	glycoepitopes					16:28	Paucimannosidic glycoepitopes	0:28	Paucimannosidic glycoepitopes	0:28	Paucimannosidic glycoepitopes inhibit tumorigenic processes in glioblastoma multiforme.
31320997	0	15	from	processes	50:58	arg1	multiforme					76:85	glioblastoma multiforme	63:85	glioblastoma multiforme	63:85	Paucimannosidic glycoepitopes inhibit tumorigenic processes in glioblastoma multiforme.
31320997	5	16	theme	epitopes	648:655	arg1	involvement					617:627	the involvement	613:627	the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion	613:743	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	7	17	from	role	1017:1020	arg1	glioblastoma					1047:1058	glioblastoma	1047:1058	glioblastoma	1047:1058	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	7	17	from	role	1017:1020	arg1	relationship					1063:1074	a relationship	1061:1074	a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease	1061:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	1	18	with	type	136:139	arg1	outcomes					159:166	poor patient outcomes	146:166	poor patient outcomes	146:166	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	7	19	theme	protective	1006:1015	arg1	role					1017:1020	a protective role	1004:1020	a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease	1004:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	1	20	theme	aggressive	118:127	arg1	multiforme					101:110	Glioblastoma multiforme	88:110	Glioblastoma multiforme	88:110	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	1	20	theme	aggressive	118:127	arg1	type					136:139	an aggressive cancer type	115:139	an aggressive cancer type with poor patient outcomes	115:166	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	0	21	theme	tumorigenic	38:48	arg1	processes					50:58	tumorigenic processes	38:58	tumorigenic processes in glioblastoma multiforme	38:85	Paucimannosidic glycoepitopes inhibit tumorigenic processes in glioblastoma multiforme.
31320997	5	22	theme	tumorigenic	660:670	arg1	adhesion					736:743	adhesion	736:743	adhesion	736:743	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	22	theme	tumorigenic	660:670	arg1	invasion					723:730	invasion	723:730	invasion	723:730	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	22	theme	tumorigenic	660:670	arg1	migration					712:720	migration	712:720	migration	712:720	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	22	theme	tumorigenic	660:670	arg1	processes					672:680	tumorigenic processes	660:680	tumorigenic processes including cell proliferation, migration, invasion and adhesion	660:743	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	22	theme	tumorigenic	660:670	arg1	proliferation					697:709	cell proliferation	692:709	cell proliferation	692:709	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	1	23	theme	cancer	129:134	arg1	multiforme					101:110	Glioblastoma multiforme	88:110	Glioblastoma multiforme	88:110	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	1	23	theme	cancer	129:134	arg1	type					136:139	an aggressive cancer type	115:139	an aggressive cancer type with poor patient outcomes	115:166	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	5	24	from	involvement	617:627	arg1	adhesion					736:743	adhesion	736:743	adhesion	736:743	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	24	from	involvement	617:627	arg1	invasion					723:730	invasion	723:730	invasion	723:730	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	24	from	involvement	617:627	arg1	migration					712:720	migration	712:720	migration	712:720	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	24	from	involvement	617:627	arg1	processes					672:680	tumorigenic processes	660:680	tumorigenic processes including cell proliferation, migration, invasion and adhesion	660:743	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	5	24	from	involvement	617:627	arg1	proliferation					697:709	cell proliferation	692:709	cell proliferation	692:709	Furthermore, we revealed the involvement of paucimannosidic epitopes in tumorigenic processes including cell proliferation, migration, invasion and adhesion.
31320997	7	25	from	evidence	992:999	arg1	glioblastoma					1047:1058	glioblastoma	1047:1058	glioblastoma	1047:1058	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	7	25	from	evidence	992:999	arg1	relationship					1063:1074	a relationship	1061:1074	a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease	1061:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	6	26	theme	paucimannose-dependent	925:946	arg1	effects					948:954	the observed paucimannose-dependent effects	912:954	the observed paucimannose-dependent effects	912:954	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	7	27	theme	in	1094:1095	arg1	support					1102:1108	further in vivo support	1086:1108	further in vivo support	1086:1108	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	2	28	theme	novel	209:213	arg1	association					215:225	a novel association	207:225	a novel association between the little studied paucimannosidic N-linked glycoepitope and glioblastoma	207:307	Interestingly, we reported previously a novel association between the little studied paucimannosidic N-linked glycoepitope and glioblastoma.
31320997	3	29	located	detected	346:353	arg2	Paucimannose					310:321	Paucimannose	310:321	Paucimannose	310:321	Paucimannose has only recently been detected in vertebrates where it exhibits a very restricted tumor-specific expression.
31320997	3	29	located	detected	346:353	arg1	vertebrates					358:368	vertebrates	358:368	vertebrates where it exhibits a very restricted tumor-specific expression	358:430	Paucimannose has only recently been detected in vertebrates where it exhibits a very restricted tumor-specific expression.
31320997	4	30	from	paucimannosylation	495:512	arg1	glioblastoma					532:543	human grade IV glioblastoma	517:543	human grade IV glioblastoma	517:543	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	4	30	from	paucimannosylation	495:512	arg1	cells					581:585	U-87MG and U-138MG glioblastoma cells	549:585	U-87MG and U-138MG glioblastoma cells	549:585	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	4	31	theme	grade	523:527	arg1	glioblastoma					532:543	human grade IV glioblastoma	517:543	human grade IV glioblastoma	517:543	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	2	32	theme	N-linked	270:277	arg1	glycoepitope					279:290	the little studied paucimannosidic N-linked glycoepitope	235:290	the little studied paucimannosidic N-linked glycoepitope	235:290	Interestingly, we reported previously a novel association between the little studied paucimannosidic N-linked glycoepitope and glioblastoma.
31320997	7	33	theme	reaching	1123:1130	arg1	benefits					1132:1139	far reaching benefits	1119:1139	far reaching benefits	1119:1139	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	4	34	theme	human	517:521	arg1	glioblastoma					532:543	human grade IV glioblastoma	517:543	human grade IV glioblastoma	517:543	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	2	35	theme	paucimannosidic	254:268	arg1	glycoepitope					279:290	the little studied paucimannosidic N-linked glycoepitope	235:290	the little studied paucimannosidic N-linked glycoepitope	235:290	Interestingly, we reported previously a novel association between the little studied paucimannosidic N-linked glycoepitope and glioblastoma.
31320997	6	36	theme	paucimannose-carrying	829:849	arg1	AHNAK					769:773	AHNAK	769:773	AHNAK which is discussed as a tumor suppressor	769:814	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	6	36	theme	paucimannose-carrying	829:849	arg1	protein					851:857	the first paucimannose-carrying protein	819:857	the first paucimannose-carrying protein in glioblastoma	819:873	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	0	37	theme	glioblastoma	63:74	arg1	multiforme					76:85	glioblastoma multiforme	63:85	glioblastoma multiforme	63:85	Paucimannosidic glycoepitopes inhibit tumorigenic processes in glioblastoma multiforme.
31320997	2	38	theme	little	239:244	arg1	glycoepitope					279:290	the little studied paucimannosidic N-linked glycoepitope	235:290	the little studied paucimannosidic N-linked glycoepitope	235:290	Interestingly, we reported previously a novel association between the little studied paucimannosidic N-linked glycoepitope and glioblastoma.
31320997	2	39	theme	studied	246:252	arg1	glycoepitope					279:290	the little studied paucimannosidic N-linked glycoepitope	235:290	the little studied paucimannosidic N-linked glycoepitope	235:290	Interestingly, we reported previously a novel association between the little studied paucimannosidic N-linked glycoepitope and glioblastoma.
31320997	6	40	theme	first	823:827	arg1	AHNAK					769:773	AHNAK	769:773	AHNAK which is discussed as a tumor suppressor	769:814	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	6	40	theme	first	823:827	arg1	protein					851:857	the first paucimannose-carrying protein	819:857	the first paucimannose-carrying protein in glioblastoma	819:873	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	1	41	theme	poor	146:149	arg1	outcomes					159:166	poor patient outcomes	146:166	poor patient outcomes	146:166	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	4	42	gly	paucimannosylation	495:512	arg1	glioblastoma					532:543	human grade IV glioblastoma	517:543	human grade IV glioblastoma	517:543	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	4	42	gly	paucimannosylation	495:512	arg1	cells					581:585	U-87MG and U-138MG glioblastoma cells	549:585	U-87MG and U-138MG glioblastoma cells	549:585	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	7	43	theme	role	1017:1020	arg1	evidence					992:999	evidence	992:999	evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease	992:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	6	44	theme	observed	916:923	arg1	effects					948:954	the observed paucimannose-dependent effects	912:954	the observed paucimannose-dependent effects	912:954	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	1	45	theme	patient	151:157	arg1	outcomes					159:166	poor patient outcomes	146:166	poor patient outcomes	146:166	Glioblastoma multiforme is an aggressive cancer type with poor patient outcomes.
31320997	4	46	theme	protein	487:493	arg1	paucimannosylation					495:512	a very high protein paucimannosylation	475:512	a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells	475:585	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	6	47	from	protein	851:857	arg1	glioblastoma					862:873	glioblastoma	862:873	glioblastoma	862:873	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	4	48	theme	high	482:485	arg1	paucimannosylation					495:512	a very high protein paucimannosylation	475:512	a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells	475:585	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	7	49	theme	further	1086:1092	arg1	support					1102:1108	further in vivo support	1086:1108	further in vivo support	1086:1108	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	7	50	theme	paucimannosylation	1025:1042	arg1	role					1017:1020	a protective role	1004:1020	a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease	1004:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	4	51	theme	U-138MG	560:566	arg1	cells					581:585	U-87MG and U-138MG glioblastoma cells	549:585	U-87MG and U-138MG glioblastoma cells	549:585	Herein, we demonstrate for the first time a very high protein paucimannosylation in human grade IV glioblastoma and U-87MG and U-138MG glioblastoma cells.
31320997	6	52	theme	tumor	799:803	arg1	suppressor					805:814	a tumor suppressor	797:814	a tumor suppressor	797:814	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	6	52	theme	tumor	799:803	arg1	AHNAK					769:773	AHNAK	769:773	AHNAK which is discussed as a tumor suppressor	769:814	Finally, we identified AHNAK which is discussed as a tumor suppressor as the first paucimannose-carrying protein in glioblastoma and show the involvement of AHNAK in the observed paucimannose-dependent effects.
31320997	7	53	from	glioblastoma	1047:1058	arg1	evidence					992:999	evidence	992:999	evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease	992:1192	This study is the first to provide evidence of a protective role of paucimannosylation in glioblastoma, a relationship that with further in vivo support may have far reaching benefits for patients suffering from this often fatal disease.
31320997	2	54	link	N-linked	270:277	arg1	glycoepitope					279:290	the little studied paucimannosidic N-linked glycoepitope	235:290	the little studied paucimannosidic N-linked glycoepitope	235:290	Interestingly, we reported previously a novel association between the little studied paucimannosidic N-linked glycoepitope and glioblastoma.
31067280	0	0	theme	computer-aided	78:91	arg1	design					98:103	computer-aided drug design	78:103	computer-aided drug design	78:103	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	4	1	theme	non-competitive	483:497	arg1	inhibitor					504:512	a non-competitive GMII inhibitor	481:512	a non-competitive GMII inhibitor	481:512	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	1	2	theme	glycoside	141:149	arg1	hydrolase					151:159	a glycoside hydrolase	139:159	a glycoside hydrolase playing a crucial role in the N-glycosylation pathway	139:213	Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway.
31067280	1	2	theme	glycoside	141:149	arg1	α-mannosidase					112:124	Golgi α-mannosidase II	106:127	Golgi α-mannosidase II (GMII)	106:134	Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway.
31067280	2	3	theme	N-linked	266:273	arg1	sugars					275:280	N-linked sugars	266:280	N-linked sugars	266:280	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	1	4	theme	Golgi	106:110	arg1	α-mannosidase					112:124	Golgi α-mannosidase II	106:127	Golgi α-mannosidase II (GMII)	106:134	Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway.
31067280	1	4	theme	Golgi	106:110	arg1	GMII					130:133	GMII	130:133	GMII	130:133	Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway.
31067280	1	4	theme	Golgi	106:110	arg1	hydrolase					151:159	a glycoside hydrolase	139:159	a glycoside hydrolase playing a crucial role in the N-glycosylation pathway	139:213	Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway.
31067280	4	5	theme	possible	585:592	arg1	site					613:616	a possible allosteric binding site	583:616	a possible allosteric binding site	583:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	0	6	theme	drug	93:96	arg1	design					98:103	computer-aided drug design	78:103	computer-aided drug design	78:103	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	2	7	theme	tumour	353:358	arg1	metastasis					360:369	tumour metastasis	353:369	tumour metastasis	353:369	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	2	8	theme	metastasis	360:369	arg1	progression					338:348	the progression	334:348	the progression of tumour metastasis	334:369	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	2	9	theme	cell	289:292	arg1	surface					294:300	the cell surface	285:300	the cell surface	285:300	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	3	10	theme	possible	392:399	arg1	target					411:416	a possible molecular target	390:416	a possible molecular target for anticancer agents	390:438	GMII therefore is a possible molecular target for anticancer agents.
31067280	3	10	theme	possible	392:399	arg1	GMII					372:375	GMII	372:375	GMII	372:375	GMII therefore is a possible molecular target for anticancer agents.
31067280	4	11	theme	design	540:545	arg1	identification					565:578	identification	565:578	identification of a possible allosteric binding site	565:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	11	theme	design	540:545	arg1	methods					547:553	computer-aided drug design methods	520:553	computer-aided drug design methods including identification of a possible allosteric binding site	520:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	11	theme	design	540:545	arg1	search					633:638	pharmacophore search	619:638	pharmacophore search	619:638	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	11	theme	design	540:545	arg1	screening					652:660	virtual screening	644:660	virtual screening	644:660	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	1	12	theme	crucial	171:177	arg1	role					179:182	a crucial role	169:182	a crucial role	169:182	Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway.
31067280	0	13	theme	potential	20:28	arg1	site					41:44	a potential allosteric site	18:44	a potential allosteric site of Golgi α-mannosidase II	18:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	0	13	theme	potential	20:28	arg1	α-mannosidase					55:67	Golgi α-mannosidase II	49:70	Golgi α-mannosidase II	49:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	4	14	theme	drug	535:538	arg1	identification					565:578	identification	565:578	identification of a possible allosteric binding site	565:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	14	theme	drug	535:538	arg1	methods					547:553	computer-aided drug design methods	520:553	computer-aided drug design methods including identification of a possible allosteric binding site	520:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	14	theme	drug	535:538	arg1	search					633:638	pharmacophore search	619:638	pharmacophore search	619:638	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	14	theme	drug	535:538	arg1	screening					652:660	virtual screening	644:660	virtual screening	644:660	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	2	15	link	N-linked	266:273	arg1	sugars					275:280	N-linked sugars	266:280	N-linked sugars	266:280	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	2	16	theme	sugars	275:280	arg1	distribution					250:261	the distribution	246:261	the distribution of N-linked sugars on the cell surface	246:300	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	4	17	theme	pharmacophore	619:631	arg1	identification					565:578	identification	565:578	identification of a possible allosteric binding site	565:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	17	theme	pharmacophore	619:631	arg1	methods					547:553	computer-aided drug design methods	520:553	computer-aided drug design methods including identification of a possible allosteric binding site	520:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	17	theme	pharmacophore	619:631	arg1	search					633:638	pharmacophore search	619:638	pharmacophore search	619:638	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	0	18	theme	site	41:44	arg1	Identification					0:13	Identification	0:13	Identification of a potential allosteric site of Golgi α-mannosidase II	0:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	4	19	theme	virtual	644:650	arg1	identification					565:578	identification	565:578	identification of a possible allosteric binding site	565:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	19	theme	virtual	644:650	arg1	methods					547:553	computer-aided drug design methods	520:553	computer-aided drug design methods including identification of a possible allosteric binding site	520:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	19	theme	virtual	644:650	arg1	screening					652:660	virtual screening	644:660	virtual screening	644:660	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	2	20	theme	various	219:225	arg1	lines					239:243	various tumour cell lines	219:243	various tumour cell lines	219:243	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	3	21	theme	molecular	401:409	arg1	target					411:416	a possible molecular target	390:416	a possible molecular target for anticancer agents	390:438	GMII therefore is a possible molecular target for anticancer agents.
31067280	3	21	theme	molecular	401:409	arg1	GMII					372:375	GMII	372:375	GMII	372:375	GMII therefore is a possible molecular target for anticancer agents.
31067280	3	22	theme	anticancer	422:431	arg1	agents					433:438	anticancer agents	422:438	anticancer agents	422:438	GMII therefore is a possible molecular target for anticancer agents.
31067280	0	23	theme	allosteric	30:39	arg1	site					41:44	a potential allosteric site	18:44	a potential allosteric site of Golgi α-mannosidase II	18:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	0	23	theme	allosteric	30:39	arg1	α-mannosidase					55:67	Golgi α-mannosidase II	49:70	Golgi α-mannosidase II	49:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	4	24	theme	inhibitor	504:512	arg1	identification					463:476	the identification	459:476	the identification of a non-competitive GMII inhibitor	459:512	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	1	25	theme	N-glycosylation	191:205	arg1	pathway					207:213	the N-glycosylation pathway	187:213	the N-glycosylation pathway	187:213	Golgi α-mannosidase II (GMII) is a glycoside hydrolase playing a crucial role in the N-glycosylation pathway.
31067280	0	26	theme	Golgi	49:53	arg1	α-mannosidase					55:67	Golgi α-mannosidase II	49:70	Golgi α-mannosidase II	49:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	4	27	theme	GMII	499:502	arg1	inhibitor					504:512	a non-competitive GMII inhibitor	481:512	a non-competitive GMII inhibitor	481:512	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	28	theme	computer-aided	520:533	arg1	identification					565:578	identification	565:578	identification of a possible allosteric binding site	565:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	28	theme	computer-aided	520:533	arg1	methods					547:553	computer-aided drug design methods	520:553	computer-aided drug design methods including identification of a possible allosteric binding site	520:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	28	theme	computer-aided	520:533	arg1	search					633:638	pharmacophore search	619:638	pharmacophore search	619:638	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	28	theme	computer-aided	520:533	arg1	screening					652:660	virtual screening	644:660	virtual screening	644:660	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	2	29	from	distribution	250:261	arg1	surface					294:300	the cell surface	285:300	the cell surface	285:300	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	4	30	theme	binding	605:611	arg1	site					613:616	a possible allosteric binding site	583:616	a possible allosteric binding site	583:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	4	31	theme	allosteric	594:603	arg1	site					613:616	a possible allosteric binding site	583:616	a possible allosteric binding site	583:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
31067280	2	32	theme	cell	234:237	arg1	lines					239:243	various tumour cell lines	219:243	various tumour cell lines	219:243	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	0	33	theme	α-mannosidase	55:67	arg1	site					41:44	a potential allosteric site	18:44	a potential allosteric site of Golgi α-mannosidase II	18:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	0	33	theme	α-mannosidase	55:67	arg1	α-mannosidase					55:67	Golgi α-mannosidase II	49:70	Golgi α-mannosidase II	49:70	Identification of a potential allosteric site of Golgi α-mannosidase II using computer-aided drug design.
31067280	2	34	theme	tumour	227:232	arg1	lines					239:243	various tumour cell lines	219:243	various tumour cell lines	219:243	In various tumour cell lines, the distribution of N-linked sugars on the cell surface is modified and correlates with the progression of tumour metastasis.
31067280	4	35	theme	site	613:616	arg1	identification					565:578	identification	565:578	identification of a possible allosteric binding site	565:616	Here, we describe the identification of a non-competitive GMII inhibitor using computer-aided drug design methods including identification of a possible allosteric binding site, pharmacophore search and virtual screening.
29920571	0	0	theme	N-linked	111:118	arg1	glycopeptides					120:132	N-linked glycopeptides	111:132	N-linked glycopeptides	111:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	1	1	theme	useful	194:199	arg1	tool					201:204	a useful tool	192:204	a useful tool in glycoproteomic analysis	192:231	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	1	1	theme	useful	194:199	arg1	chromatography					166:179	Hydrophilic interaction liquid chromatography	135:179	Hydrophilic interaction liquid chromatography (HILIC)	135:187	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	3	2	from	group	568:572	arg1	Au					593:594	Au	593:594	Au	593:594	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	2	from	group	568:572	arg1	glutathione					577:587	glutathione	577:587	glutathione	577:587	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	4	3	theme	glutathione	637:647	arg1	responsiveness					704:717	strong magnetic responsiveness	688:717	strong magnetic responsiveness of magnetic nanoparticles	688:743	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	3	theme	glutathione	637:647	arg1	area					668:671	the large surface area	650:671	the large surface area of the MOF	650:682	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	3	theme	glutathione	637:647	arg1	hydrophilicity					619:632	the high hydrophilicity	610:632	the high hydrophilicity of glutathione	610:647	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	3	4	theme	denoted	437:443	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	4	theme	denoted	437:443	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	2	5	from	activities	371:380	arg1	ubiquitous					346:355	ubiquitous	346:355	ubiquitous	346:355	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	5	6	theme	complex	958:964	arg1	samples					977:983	complex biological samples	958:983	complex biological samples	958:983	Furthermore, it also achieved outstanding performance in enriching glycopeptides from complex biological samples.
29920571	4	7	theme	@	766:766	arg1	GSH					770:772	the as-prepared mMOF@Au@GSH	746:772	the as-prepared mMOF@Au@GSH	746:772	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	8	theme	high	614:617	arg1	hydrophilicity					619:632	the high hydrophilicity	610:632	the high hydrophilicity of glutathione	610:647	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	2	9	theme	biological	360:369	arg1	activities					371:380	biological activities	360:380	biological activities	360:380	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	5	10	theme	biological	966:975	arg1	samples					977:983	complex biological samples	958:983	complex biological samples	958:983	Furthermore, it also achieved outstanding performance in enriching glycopeptides from complex biological samples.
29920571	4	11	theme	@	769:769	arg1	GSH					770:772	the as-prepared mMOF@Au@GSH	746:772	the as-prepared mMOF@Au@GSH	746:772	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	3	12	theme	magnetic	519:526	arg1	MOFs					528:531	Au-immobilized magnetic MOFs	504:531	Au-immobilized magnetic MOFs	504:531	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	4	13	theme	mMOF	762:765	arg1	GSH					770:772	the as-prepared mMOF@Au@GSH	746:772	the as-prepared mMOF@Au@GSH	746:772	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	14	theme	high	784:787	arg1	selectivity					789:799	high selectivity	784:799	high selectivity (1 : 100)	784:809	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	14	theme	high	784:787	arg1	 100					805:808	 100	805:808	 100	805:808	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	3	15	theme	@	455:455	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	15	theme	@	455:455	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	6	16	theme	human	1077:1081	arg1	serum					1083:1087	only 2 μL human serum	1067:1087	only 2 μL human serum	1067:1087	In all, 273 glycopeptides corresponding to 94 glycoproteins were identified from only 2 μL human serum.
29920571	5	17	gly	glycopeptides	939:951	arg2	glycopeptides					939:951	glycopeptides	939:951	glycopeptides	939:951	Furthermore, it also achieved outstanding performance in enriching glycopeptides from complex biological samples.
29920571	3	18	theme	thiol	562:566	arg1	group					568:572	the thiol group	558:572	the thiol group in glutathione and Au	558:594	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	19	theme	hydrophilic	400:410	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	19	theme	hydrophilic	400:410	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	6	20	theme	μL	1074:1075	arg1	serum					1083:1087	only 2 μL human serum	1067:1087	only 2 μL human serum	1067:1087	In all, 273 glycopeptides corresponding to 94 glycoproteins were identified from only 2 μL human serum.
29920571	0	21	theme	tripeptide-functionalized	12:36	arg1	frameworks					61:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks	0:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides	0:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	4	22	theme	fmol	838:841	arg1	sensitivity					821:831	great sensitivity	815:831	great sensitivity (0.5 fmol μL-1)	815:847	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	22	theme	fmol	838:841	arg1	μL-1					843:846	0.5 fmol μL-1	834:846	0.5 fmol μL-1	834:846	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	0	23	gly	glycopeptides	120:132	arg2	glycopeptides					120:132	N-linked glycopeptides	111:132	N-linked glycopeptides	111:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	1	24	theme	glycoproteomic	209:222	arg1	analysis					224:231	glycoproteomic analysis	209:231	glycoproteomic analysis	209:231	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	0	25	theme	Hydrophilic	0:10	arg1	frameworks					61:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks	0:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides	0:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	4	26	theme	as-prepared	750:760	arg1	GSH					770:772	the as-prepared mMOF@Au@GSH	746:772	the as-prepared mMOF@Au@GSH	746:772	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	27	gly	glycopeptides	857:869	arg2	glycopeptides					857:869	glycopeptides	857:869	glycopeptides	857:869	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	0	28	theme	metal-organic	47:59	arg1	frameworks					61:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks	0:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides	0:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	1	29	theme	Hydrophilic	135:145	arg1	tool					201:204	a useful tool	192:204	a useful tool in glycoproteomic analysis	192:231	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	1	29	theme	Hydrophilic	135:145	arg1	HILIC					182:186	HILIC	182:186	HILIC	182:186	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	1	29	theme	Hydrophilic	135:145	arg1	chromatography					166:179	Hydrophilic interaction liquid chromatography	135:179	Hydrophilic interaction liquid chromatography (HILIC)	135:187	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	4	30	theme	large	654:658	arg1	area					668:671	the large surface area	650:671	the large surface area of the MOF	650:682	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	0	31	theme	magnetic	38:45	arg1	frameworks					61:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks	0:70	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides	0:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	1	32	theme	interaction	147:157	arg1	tool					201:204	a useful tool	192:204	a useful tool in glycoproteomic analysis	192:231	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	1	32	theme	interaction	147:157	arg1	HILIC					182:186	HILIC	182:186	HILIC	182:186	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	1	32	theme	interaction	147:157	arg1	chromatography					166:179	Hydrophilic interaction liquid chromatography	135:179	Hydrophilic interaction liquid chromatography (HILIC)	135:187	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	6	33	gly	glycopeptides	998:1010	arg2	glycopeptides					998:1010	273 glycopeptides	994:1010	273 glycopeptides corresponding to 94 glycoproteins	994:1044	In all, 273 glycopeptides corresponding to 94 glycoproteins were identified from only 2 μL human serum.
29920571	3	34	theme	@	452:452	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	34	theme	@	452:452	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	6	35	gly	glycoproteins	1032:1044	arg1	glycoproteins					1032:1044	94 glycoproteins	1029:1044	94 glycoproteins	1029:1044	In all, 273 glycopeptides corresponding to 94 glycoproteins were identified from only 2 μL human serum.
29920571	2	36	theme	well-known	257:266	arg1	tripeptide					281:290	a well-known zwitterionic tripeptide	255:290	a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility	255:337	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	2	36	theme	well-known	257:266	arg1	Glutathione					234:244	Glutathione	234:244	Glutathione (GSH)	234:250	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	4	37	theme	MOF	680:682	arg1	responsiveness					704:717	strong magnetic responsiveness	688:717	strong magnetic responsiveness of magnetic nanoparticles	688:743	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	37	theme	MOF	680:682	arg1	area					668:671	the large surface area	650:671	the large surface area of the MOF	650:682	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	37	theme	MOF	680:682	arg1	hydrophilicity					619:632	the high hydrophilicity	610:632	the high hydrophilicity of glutathione	610:647	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	3	38	theme	Au	453:454	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	38	theme	Au	453:454	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	2	39	with	tripeptide	281:290	arg1	biocompatibility					322:337	biocompatibility	322:337	biocompatibility	322:337	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	2	39	with	tripeptide	281:290	arg1	hydrophilicity					303:316	great hydrophilicity	297:316	great hydrophilicity	297:316	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	3	40	theme	metal-organic	412:424	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	40	theme	metal-organic	412:424	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	0	41	link	N-linked	111:118	arg1	glycopeptides					120:132	N-linked glycopeptides	111:132	N-linked glycopeptides	111:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	4	42	theme	surface	660:666	arg1	area					668:671	the large surface area	650:671	the large surface area of the MOF	650:682	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	3	43	theme	as	445:446	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	43	theme	as	445:446	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	4	44	theme	great	815:819	arg1	sensitivity					821:831	great sensitivity	815:831	great sensitivity (0.5 fmol μL-1)	815:847	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	44	theme	great	815:819	arg1	μL-1					843:846	0.5 fmol μL-1	834:846	0.5 fmol μL-1	834:846	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	1	45	theme	liquid	159:164	arg1	tool					201:204	a useful tool	192:204	a useful tool in glycoproteomic analysis	192:231	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	1	45	theme	liquid	159:164	arg1	HILIC					182:186	HILIC	182:186	HILIC	182:186	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	1	45	theme	liquid	159:164	arg1	chromatography					166:179	Hydrophilic interaction liquid chromatography	135:179	Hydrophilic interaction liquid chromatography (HILIC)	135:187	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	3	46	theme	mMOF	448:451	arg1	GSH					456:458	denoted as mMOF@Au@GSH	437:458	denoted as mMOF@Au@GSH	437:458	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	3	46	theme	mMOF	448:451	arg1	framework					426:434	a hydrophilic metal-organic framework	398:434	a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH)	398:459	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	4	47	theme	magnetic	722:729	arg1	nanoparticles					731:743	magnetic nanoparticles	722:743	magnetic nanoparticles	722:743	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	48	with	Endowed	597:603	arg1	responsiveness					704:717	strong magnetic responsiveness	688:717	strong magnetic responsiveness of magnetic nanoparticles	688:743	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	48	with	Endowed	597:603	arg1	area					668:671	the large surface area	650:671	the large surface area of the MOF	650:682	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	48	with	Endowed	597:603	arg1	hydrophilicity					619:632	the high hydrophilicity	610:632	the high hydrophilicity of glutathione	610:647	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	49	theme	nanoparticles	731:743	arg1	responsiveness					704:717	strong magnetic responsiveness	688:717	strong magnetic responsiveness of magnetic nanoparticles	688:743	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	49	theme	nanoparticles	731:743	arg1	area					668:671	the large surface area	650:671	the large surface area of the MOF	650:682	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	4	49	theme	nanoparticles	731:743	arg1	hydrophilicity					619:632	the high hydrophilicity	610:632	the high hydrophilicity of glutathione	610:647	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	2	50	theme	great	297:301	arg1	hydrophilicity					303:316	great hydrophilicity	297:316	great hydrophilicity	297:316	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	3	51	from	glutathione	489:499	arg1	MOFs					528:531	Au-immobilized magnetic MOFs	504:531	Au-immobilized magnetic MOFs	504:531	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	5	52	theme	outstanding	902:912	arg1	performance					914:924	outstanding performance	902:924	outstanding performance	902:924	Furthermore, it also achieved outstanding performance in enriching glycopeptides from complex biological samples.
29920571	4	53	theme	Au	767:768	arg1	GSH					770:772	the as-prepared mMOF@Au@GSH	746:772	the as-prepared mMOF@Au@GSH	746:772	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	3	54	theme	Au-immobilized	504:517	arg1	MOFs					528:531	Au-immobilized magnetic MOFs	504:531	Au-immobilized magnetic MOFs	504:531	In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au.
29920571	4	55	theme	magnetic	695:702	arg1	responsiveness					704:717	strong magnetic responsiveness	688:717	strong magnetic responsiveness of magnetic nanoparticles	688:743	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	0	56	theme	efficient	87:95	arg1	enrichment					97:106	the highly efficient enrichment	76:106	the highly efficient enrichment of N-linked glycopeptides	76:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
29920571	2	57	theme	zwitterionic	268:279	arg1	tripeptide					281:290	a well-known zwitterionic tripeptide	255:290	a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility	255:337	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	2	57	theme	zwitterionic	268:279	arg1	Glutathione					234:244	Glutathione	234:244	Glutathione (GSH)	234:250	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	1	58	from	tool	201:204	arg1	analysis					224:231	glycoproteomic analysis	209:231	glycoproteomic analysis	209:231	Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis.
29920571	4	59	theme	strong	688:693	arg1	responsiveness					704:717	strong magnetic responsiveness	688:717	strong magnetic responsiveness of magnetic nanoparticles	688:743	Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides.
29920571	2	60	from	ubiquitous	346:355	arg1	activities					371:380	biological activities	360:380	biological activities	360:380	Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and biocompatibility and is ubiquitous in biological activities.
29920571	0	61	theme	glycopeptides	120:132	arg1	enrichment					97:106	the highly efficient enrichment	76:106	the highly efficient enrichment of N-linked glycopeptides	76:132	Hydrophilic tripeptide-functionalized magnetic metal-organic frameworks for the highly efficient enrichment of N-linked glycopeptides.
31066275	1	0	theme	core	148:151	arg1	pentasaccharide					162:176	the core N-glycan pentasaccharide	144:176	the core N-glycan pentasaccharide	144:176	Presented herein are two complementary approaches to the synthesis of the core N-glycan pentasaccharide.
31066275	1	1	theme	N-glycan	153:160	arg1	pentasaccharide					162:176	the core N-glycan pentasaccharide	144:176	the core N-glycan pentasaccharide	144:176	Presented herein are two complementary approaches to the synthesis of the core N-glycan pentasaccharide.
31066275	2	2	theme	linkage	358:364	arg1	introduction					325:336	the highly diastereoselective introduction	295:336	the highly diastereoselective introduction of the β-mannosidic linkage at room temperature	295:384	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	2	3	theme	method	284:289	arg1	use					239:241	use	239:241	use of the H-bond-mediated aglycone delivery method	239:289	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	2	4	theme	delivery	275:282	arg1	method					284:289	the H-bond-mediated aglycone delivery method	246:289	the H-bond-mediated aglycone delivery method	246:289	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	2	5	theme	aglycone	266:273	arg1	method					284:289	the H-bond-mediated aglycone delivery method	246:289	the H-bond-mediated aglycone delivery method	246:289	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	2	6	from	approach	211:218	arg1	solution					223:230	solution	223:230	solution	223:230	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	1	7	theme	pentasaccharide	162:176	arg1	synthesis					131:139	the synthesis	127:139	the synthesis of the core N-glycan pentasaccharide	127:176	Presented herein are two complementary approaches to the synthesis of the core N-glycan pentasaccharide.
31066275	3	8	theme	core	408:411	arg1	pentasaccharide					413:427	the core pentasaccharide	404:427	the core pentasaccharide	404:427	The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach.
31066275	4	9	theme	overall	532:538	arg1	swift					553:557	swift	553:557	swift	553:557	The overall assembly was swift (8 h) and efficient (31%).
31066275	4	9	theme	overall	532:538	arg1	h					562:562	8 h	560:562	8 h	560:562	The overall assembly was swift (8 h) and efficient (31%).
31066275	4	9	theme	overall	532:538	arg1	assembly					540:547	The overall assembly	528:547	The overall assembly	528:547	The overall assembly was swift (8 h) and efficient (31%).
31066275	2	10	theme	H-bond-mediated	250:264	arg1	method					284:289	the H-bond-mediated aglycone delivery method	246:289	the H-bond-mediated aglycone delivery method	246:289	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	4	11	dep	efficient	569:577	arg1	%					582:582	31%	580:582	31%	580:582	The overall assembly was swift (8 h) and efficient (31%).
31066275	2	12	theme	diastereoselective	306:323	arg1	introduction					325:336	the highly diastereoselective introduction	295:336	the highly diastereoselective introduction of the β-mannosidic linkage at room temperature	295:384	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	0	13	theme	Manual	0:5	arg1	Syntheses					21:29	Manual and Automated Syntheses	0:29	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans	0:71	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.
31066275	2	14	from	temperature	374:384	arg1	introduction					325:336	the highly diastereoselective introduction	295:336	the highly diastereoselective introduction of the β-mannosidic linkage at room temperature	295:384	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	3	15	theme	chromatography-assisted	484:506	arg1	approach					518:525	an high-performance liquid chromatography-assisted automated approach	457:525	an high-performance liquid chromatography-assisted automated approach	457:525	The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach.
31066275	0	16	theme	Automated	11:19	arg1	Syntheses					21:29	Manual and Automated Syntheses	0:29	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans	0:71	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.
31066275	1	17	theme	complementary	99:111	arg1	approaches					113:122	two complementary approaches	95:122	two complementary approaches to the synthesis of the core N-glycan pentasaccharide	95:176	Presented herein are two complementary approaches to the synthesis of the core N-glycan pentasaccharide.
31066275	1	17	theme	complementary	99:111	arg1	Presented					74:82	Presented	74:82	Presented	74:82	Presented herein are two complementary approaches to the synthesis of the core N-glycan pentasaccharide.
31066275	3	18	theme	automated	508:516	arg1	approach					518:525	an high-performance liquid chromatography-assisted automated approach	457:525	an high-performance liquid chromatography-assisted automated approach	457:525	The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach.
31066275	3	19	theme	pentasaccharide	413:427	arg1	synthesis					391:399	The synthesis	387:399	The synthesis of the core pentasaccharide	387:427	The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach.
31066275	3	20	theme	high-performance	460:475	arg1	approach					518:525	an high-performance liquid chromatography-assisted automated approach	457:525	an high-performance liquid chromatography-assisted automated approach	457:525	The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach.
31066275	3	21	theme	liquid	477:482	arg1	approach					518:525	an high-performance liquid chromatography-assisted automated approach	457:525	an high-performance liquid chromatography-assisted automated approach	457:525	The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach.
31066275	0	22	theme	Glycoprotein	47:58	arg1	Glycans					65:71	the N-Linked Glycoprotein Core Glycans	34:71	the N-Linked Glycoprotein Core Glycans	34:71	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.
31066275	4	23	dep	swift	553:557	arg1	swift					553:557	swift	553:557	swift	553:557	The overall assembly was swift (8 h) and efficient (31%).
31066275	4	23	dep	swift	553:557	arg1	h					562:562	8 h	560:562	8 h	560:562	The overall assembly was swift (8 h) and efficient (31%).
31066275	4	23	dep	swift	553:557	arg1	assembly					540:547	The overall assembly	528:547	The overall assembly	528:547	The overall assembly was swift (8 h) and efficient (31%).
31066275	2	24	theme	β-mannosidic	345:356	arg1	linkage					358:364	the β-mannosidic linkage	341:364	the β-mannosidic linkage	341:364	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	0	25	theme	N-Linked	38:45	arg1	Glycans					65:71	the N-Linked Glycoprotein Core Glycans	34:71	the N-Linked Glycoprotein Core Glycans	34:71	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.
31066275	2	26	theme	manual	204:209	arg1	approach					211:218	a traditional manual approach	190:218	a traditional manual approach in solution	190:230	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	2	26	theme	manual	204:209	arg1	first					183:187	first	183:187	first	183:187	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	2	27	theme	traditional	192:202	arg1	approach					211:218	a traditional manual approach	190:218	a traditional manual approach in solution	190:230	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	2	27	theme	traditional	192:202	arg1	first					183:187	first	183:187	first	183:187	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
31066275	0	28	theme	Glycans	65:71	arg1	Syntheses					21:29	Manual and Automated Syntheses	0:29	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans	0:71	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.
31066275	0	29	theme	Core	60:63	arg1	Glycans					65:71	the N-Linked Glycoprotein Core Glycans	34:71	the N-Linked Glycoprotein Core Glycans	34:71	Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.
31066275	2	30	theme	room	369:372	arg1	temperature					374:384	room temperature	369:384	room temperature	369:384	The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the β-mannosidic linkage at room temperature.
29942801	5	0	theme	cellular	813:820	arg1	processes					822:830	different cellular processes	803:830	different cellular processes	803:830	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	6	1	theme	phenomenon	964:973	arg1	occurrence					945:954	the occurrence	941:954	the occurrence of this phenomenon during sperm maturation	941:997	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	6	1	theme	phenomenon	964:973	arg1	system					899:904	the O-GlcNAcylation system	879:904	the O-GlcNAcylation system in the male reproductive tract	879:935	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	10	2	from	role	1461:1464	arg1	process					1515:1521	this process	1510:1521	this process	1510:1521	Our results indicate that the modulation of O-GlcNAcylation takes place during sperm maturation and suggest a role for this post-translational modification in this process.
29942801	7	3	from	present	1101:1107	arg1	sperm					1154:1158	immature caput sperm	1139:1158	immature caput sperm	1139:1158	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	3	from	present	1101:1107	arg1	epididymis					1124:1133	epididymis	1124:1133	epididymis	1124:1133	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	3	from	present	1101:1107	arg1	testis					1116:1121	testis	1116:1121	testis	1116:1121	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	10	4	theme	post-translational	1475:1492	arg1	modification					1494:1505	this post-translational modification	1470:1505	this post-translational modification	1470:1505	Our results indicate that the modulation of O-GlcNAcylation takes place during sperm maturation and suggest a role for this post-translational modification in this process.
29942801	8	5	theme	cauda	1209:1213	arg1	sperm					1215:1219	mature cauda sperm	1202:1219	mature cauda sperm	1202:1219	Its presence is significantly reduced in mature cauda sperm.
29942801	1	6	theme	fertilizing	172:182	arg1	capacity					184:191	fertilizing capacity	172:191	fertilizing capacity	172:191	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	4	7	theme	post-translational	584:601	arg1	modifications					603:615	post-translational modifications	584:615	post-translational modifications	584:615	Sperm are both transcriptionally and translationally silent, therefore post-translational modifications are essential to regulate their function.
29942801	8	8	theme	mature	1202:1207	arg1	sperm					1215:1219	mature cauda sperm	1202:1219	mature cauda sperm	1202:1219	Its presence is significantly reduced in mature cauda sperm.
29942801	0	9	from	Changes	0:6	arg1	O-GlcNAcylation					19:33	Protein O-GlcNAcylation	11:33	Protein O-GlcNAcylation	11:33	Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation.
29942801	7	10	theme	caput	1148:1152	arg1	sperm					1154:1158	immature caput sperm	1139:1158	immature caput sperm	1139:1158	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	11	theme	O-GlcNAc	1026:1033	arg1	OGT					1048:1050	OGT	1048:1050	OGT	1048:1050	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	11	theme	O-GlcNAc	1026:1033	arg1	transferase					1035:1045	O-GlcNAc transferase	1026:1045	O-GlcNAc transferase (OGT)	1026:1051	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	11	theme	O-GlcNAc	1026:1033	arg1	enzyme					1058:1063	the enzyme	1054:1063	the enzyme responsible for O-GlcNAcylation	1054:1095	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	1	12	theme	female	265:270	arg1	tract					285:289	the female reproductive tract	261:289	the female reproductive tract	261:289	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	7	13	located	present	1101:1107	arg1	sperm					1154:1158	immature caput sperm	1139:1158	immature caput sperm	1139:1158	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	13	located	present	1101:1107	arg2	enzyme					1058:1063	the enzyme	1054:1063	the enzyme responsible for O-GlcNAcylation	1054:1095	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	13	located	present	1101:1107	arg1	epididymis					1124:1133	epididymis	1124:1133	epididymis	1124:1133	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	13	located	present	1101:1107	arg2	transferase					1035:1045	O-GlcNAc transferase	1026:1045	O-GlcNAc transferase (OGT)	1026:1051	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	13	located	present	1101:1107	arg2	OGT					1048:1050	OGT	1048:1050	OGT	1048:1050	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	13	located	present	1101:1107	arg1	testis					1116:1121	testis	1116:1121	testis	1116:1121	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	1	14	theme	reproductive	272:283	arg1	tract					285:289	the female reproductive tract	261:289	the female reproductive tract	261:289	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	6	15	from	occurrence	945:954	arg1	tract					931:935	the male reproductive tract	909:935	the male reproductive tract	909:935	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	9	16	theme	caput	1236:1240	arg1	sperm					1242:1246	caput sperm	1236:1246	caput sperm	1236:1246	Consistently, caput sperm display high levels of O-GlcNAcylation when compared to mature cauda sperm, where it is mostly absent.
29942801	5	17	theme	phosphorylation	784:798	arg1	modification					682:693	The post-translational modification	659:693	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc)	659:754	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	5	17	theme	phosphorylation	784:798	arg1	counterpart					769:779	a counterpart	767:779	a counterpart of phosphorylation in different cellular processes	767:830	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	7	18	theme	immature	1139:1146	arg1	sperm					1154:1158	immature caput sperm	1139:1158	immature caput sperm	1139:1158	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	19	from	testis	1116:1121	arg1	present					1101:1107	present	1101:1107	present	1101:1107	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	2	20	theme	motility	403:410	arg1	acquisition					388:398	the acquisition	384:398	the acquisition of motility	384:410	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	2	20	theme	motility	403:410	arg1	them					422:425	them	422:425	them	422:425	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	2	20	theme	motility	403:410	arg1	one					415:417	one	415:417	one	415:417	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	5	21	theme	post-translational	663:680	arg1	modification					682:693	The post-translational modification	659:693	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc)	659:754	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	5	21	theme	post-translational	663:680	arg1	counterpart					769:779	a counterpart	767:779	a counterpart of phosphorylation in different cellular processes	767:830	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	5	22	theme	β-N-acetylglucosamine	723:743	arg1	addition					702:709	the addition	698:709	the addition of O-linked β-N-acetylglucosamine (O-GlcNAc)	698:754	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	9	23	theme	high	1256:1259	arg1	levels					1261:1266	high levels	1256:1266	high levels of O-GlcNAcylation	1256:1285	Consistently, caput sperm display high levels of O-GlcNAcylation when compared to mature cauda sperm, where it is mostly absent.
29942801	3	24	theme	molecular	432:440	arg1	basis					442:446	The molecular basis	428:446	The molecular basis of the regulation of this process	428:480	The molecular basis of the regulation of this process is still not fully understood.
29942801	6	25	from	system	899:904	arg1	tract					931:935	the male reproductive tract	909:935	the male reproductive tract	909:935	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	7	26	from	epididymis	1124:1133	arg1	present					1101:1107	present	1101:1107	present	1101:1107	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	5	27	link	O-linked	714:721	arg1	O-GlcNAc					746:753	O-GlcNAc	746:753	O-GlcNAc	746:753	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	5	27	link	O-linked	714:721	arg1	β-N-acetylglucosamine					723:743	O-linked β-N-acetylglucosamine	714:743	O-linked β-N-acetylglucosamine (O-GlcNAc)	714:754	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	9	28	theme	O-GlcNAcylation	1271:1285	arg1	levels					1261:1266	high levels	1256:1266	high levels of O-GlcNAcylation	1256:1285	Consistently, caput sperm display high levels of O-GlcNAcylation when compared to mature cauda sperm, where it is mostly absent.
29942801	0	29	theme	Protein	11:17	arg1	O-GlcNAcylation					19:33	Protein O-GlcNAcylation	11:33	Protein O-GlcNAcylation	11:33	Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation.
29942801	6	30	theme	reproductive	918:929	arg1	tract					931:935	the male reproductive tract	909:935	the male reproductive tract	909:935	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	2	31	theme	maturational	362:373	arg1	changes					375:381	several maturational changes	354:381	several maturational changes	354:381	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	2	32	theme	them	422:425	arg1	acquisition					388:398	the acquisition	384:398	the acquisition of motility	384:410	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	2	32	theme	them	422:425	arg1	them					422:425	them	422:425	them	422:425	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	2	32	theme	them	422:425	arg1	one					415:417	one	415:417	one	415:417	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	0	33	theme	Mouse	42:46	arg1	Maturation					65:74	Mouse Epididymal Sperm Maturation	42:74	Mouse Epididymal Sperm Maturation	42:74	Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation.
29942801	6	34	theme	male	913:916	arg1	tract					931:935	the male reproductive tract	909:935	the male reproductive tract	909:935	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	1	35	dep	sperm	194:198	arg1	maturation					200:209	maturation	200:209	maturation in the male epididymis	200:232	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	7	36	attach	present	1101:1107	arg1	sperm					1154:1158	immature caput sperm	1139:1158	immature caput sperm	1139:1158	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	36	attach	present	1101:1107	arg2	enzyme					1058:1063	the enzyme	1054:1063	the enzyme responsible for O-GlcNAcylation	1054:1095	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	36	attach	present	1101:1107	arg1	epididymis					1124:1133	epididymis	1124:1133	epididymis	1124:1133	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	36	attach	present	1101:1107	arg2	transferase					1035:1045	O-GlcNAc transferase	1026:1045	O-GlcNAc transferase (OGT)	1026:1051	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	36	attach	present	1101:1107	arg2	OGT					1048:1050	OGT	1048:1050	OGT	1048:1050	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	36	attach	present	1101:1107	arg1	testis					1116:1121	testis	1116:1121	testis	1116:1121	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	1	37	theme	male	218:221	arg1	epididymis					223:232	the male epididymis	214:232	the male epididymis	214:232	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	3	38	theme	regulation	455:464	arg1	basis					442:446	The molecular basis	428:446	The molecular basis of the regulation of this process	428:480	The molecular basis of the regulation of this process is still not fully understood.
29942801	0	39	theme	Sperm	59:63	arg1	Maturation					65:74	Mouse Epididymal Sperm Maturation	42:74	Mouse Epididymal Sperm Maturation	42:74	Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation.
29942801	7	40	from	sperm	1154:1158	arg1	present					1101:1107	present	1101:1107	present	1101:1107	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	5	41	theme	O-linked	714:721	arg1	O-GlcNAc					746:753	O-GlcNAc	746:753	O-GlcNAc	746:753	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	5	41	theme	O-linked	714:721	arg1	β-N-acetylglucosamine					723:743	O-linked β-N-acetylglucosamine	714:743	O-linked β-N-acetylglucosamine (O-GlcNAc)	714:754	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	5	42	from	counterpart	769:779	arg1	processes					822:830	different cellular processes	803:830	different cellular processes	803:830	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
29942801	7	43	theme	responsible	1065:1075	arg1	transferase					1035:1045	O-GlcNAc transferase	1026:1045	O-GlcNAc transferase (OGT)	1026:1051	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	7	43	theme	responsible	1065:1075	arg1	enzyme					1058:1063	the enzyme	1054:1063	the enzyme responsible for O-GlcNAcylation	1054:1095	Our results indicate that O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAcylation, is present in the testis, epididymis and immature caput sperm.
29942801	2	44	theme	several	354:360	arg1	changes					375:381	several maturational changes	354:381	several maturational changes	354:381	During their transit through the epididymis, sperm experience several maturational changes; the acquisition of motility is one of them.
29942801	0	45	theme	Epididymal	48:57	arg1	Maturation					65:74	Mouse Epididymal Sperm Maturation	42:74	Mouse Epididymal Sperm Maturation	42:74	Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation.
29942801	1	46	from	capacitation	245:256	arg1	tract					285:289	the female reproductive tract	261:289	the female reproductive tract	261:289	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	9	47	theme	mature	1304:1309	arg1	sperm					1317:1321	mature cauda sperm	1304:1321	mature cauda sperm	1304:1321	Consistently, caput sperm display high levels of O-GlcNAcylation when compared to mature cauda sperm, where it is mostly absent.
29942801	6	48	theme	sperm	982:986	arg1	maturation					988:997	sperm maturation	982:997	sperm maturation	982:997	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	6	49	theme	O-GlcNAcylation	883:897	arg1	system					899:904	the O-GlcNAcylation system	879:904	the O-GlcNAcylation system in the male reproductive tract	879:935	Therefore, our work was aimed to characterize the O-GlcNAcylation system in the male reproductive tract and the occurrence of this phenomenon during sperm maturation.
29942801	10	50	theme	sperm	1430:1434	arg1	maturation					1436:1445	sperm maturation	1430:1445	sperm maturation	1430:1445	Our results indicate that the modulation of O-GlcNAcylation takes place during sperm maturation and suggest a role for this post-translational modification in this process.
29942801	1	51	theme	sequential	121:130	arg1	processes					145:153	two sequential maturational processes	117:153	two sequential maturational processes	117:153	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	9	52	theme	cauda	1311:1315	arg1	sperm					1317:1321	mature cauda sperm	1304:1321	mature cauda sperm	1304:1321	Consistently, caput sperm display high levels of O-GlcNAcylation when compared to mature cauda sperm, where it is mostly absent.
29942801	1	53	from	sperm	194:198	arg1	tract					285:289	the female reproductive tract	261:289	the female reproductive tract	261:289	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	1	54	theme	maturational	132:143	arg1	processes					145:153	two sequential maturational processes	117:153	two sequential maturational processes	117:153	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	3	55	theme	process	474:480	arg1	regulation					455:464	the regulation	451:464	the regulation of this process	451:480	The molecular basis of the regulation of this process is still not fully understood.
29942801	10	56	theme	O-GlcNAcylation	1395:1409	arg1	modulation					1381:1390	the modulation	1377:1390	the modulation of O-GlcNAcylation	1377:1409	Our results indicate that the modulation of O-GlcNAcylation takes place during sperm maturation and suggest a role for this post-translational modification in this process.
29942801	1	57	from	maturation	200:209	arg1	epididymis					223:232	the male epididymis	214:232	the male epididymis	214:232	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	1	58	theme	sperm	239:243	arg1	capacitation					245:256	sperm capacitation	239:256	sperm capacitation	239:256	After leaving the testis, sperm undergo two sequential maturational processes before acquiring fertilizing capacity: sperm maturation in the male epididymis, and sperm capacitation in the female reproductive tract.
29942801	5	59	theme	different	803:811	arg1	processes					822:830	different cellular processes	803:830	different cellular processes	803:830	The post-translational modification by the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) can act as a counterpart of phosphorylation in different cellular processes.
31164864	7	0	theme	expression	1182:1191	arg1	manipulation					1155:1166	manipulation	1155:1166	manipulation of OGT or OGA expression or activity	1155:1203	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	7	1	theme	OGT	1171:1173	arg1	manipulation					1155:1166	manipulation	1155:1166	manipulation of OGT or OGA expression or activity	1155:1203	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	11	2	from	activity	1845:1852	arg1	cells					1859:1863	β cells	1857:1863	β cells	1857:1863	Altogether, our study reveals that O-GlcNAcylation represents an important regulatory mechanism for TxNIP activity in β cells.
31164864	0	3	attach	Links	16:20	arg2	O-GlcNacylation					0:14	O-GlcNacylation	0:14	O-GlcNacylation	0:14	O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells.
31164864	0	3	attach	Links	16:20	arg1	Activation					44:53	Inflammasome Activation	31:53	Inflammasome Activation in Pancreatic β Cells	31:75	O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells.
31164864	4	4	theme	pancreatic	611:620	arg1	cells					624:628	pancreatic β cells	611:628	pancreatic β cells	611:628	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	5	5	theme	serine/threonine	893:908	arg1	residues					910:917	serine/threonine residues	893:917	serine/threonine residues on target proteins	893:936	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	11	6	theme	important	1804:1812	arg1	mechanism					1825:1833	an important regulatory mechanism	1801:1833	an important regulatory mechanism for TxNIP activity in β cells	1801:1863	Altogether, our study reveals that O-GlcNAcylation represents an important regulatory mechanism for TxNIP activity in β cells.
31164864	4	7	link	O-linked	666:673	arg1	O-GlcNAcylation					698:712	O-GlcNAcylation	698:712	O-GlcNAcylation	698:712	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	4	7	link	O-linked	666:673	arg1	β-N-acetylglucosamine					675:695	O-linked β-N-acetylglucosamine	666:695	O-linked β-N-acetylglucosamine (O-GlcNAcylation)	666:713	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	10	8	theme	INS1	1586:1589	arg1	cells					1598:1602	HEK293 or INS1 832/13 cells	1576:1602	HEK293 or INS1 832/13 cells	1576:1602	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
31164864	3	9	with	interaction	387:397	arg1	NLRP3					438:442	the inflammasome protein NLRP3	413:442	the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3)	413:482	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	11	10	theme	regulatory	1814:1823	arg1	mechanism					1825:1833	an important regulatory mechanism	1801:1833	an important regulatory mechanism for TxNIP activity in β cells	1801:1863	Altogether, our study reveals that O-GlcNAcylation represents an important regulatory mechanism for TxNIP activity in β cells.
31164864	4	11	theme	O-linked	666:673	arg1	O-GlcNAcylation					698:712	O-GlcNAcylation	698:712	O-GlcNAcylation	698:712	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	4	11	theme	O-linked	666:673	arg1	β-N-acetylglucosamine					675:695	O-linked β-N-acetylglucosamine	666:695	O-linked β-N-acetylglucosamine (O-GlcNAcylation)	666:713	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	7	12	theme	O-GlcNAcylation	1123:1137	arg1	pathway					1139:1145	the O-GlcNAcylation pathway	1119:1145	the O-GlcNAcylation pathway	1119:1145	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	3	13	theme	interleukin-1	496:508	arg1	IL1β					513:516	IL1β	513:516	IL1β	513:516	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	13	theme	interleukin-1	496:508	arg1	β					510:510	interleukin-1 β	496:510	interleukin-1 β (IL1β) secretion	496:527	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	14	theme	inflammasome	417:428	arg1	NLRP3					438:442	the inflammasome protein NLRP3	413:442	the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3)	413:482	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	15	theme	Recent	330:335	arg1	studies					337:343	Recent studies	330:343	Recent studies	330:343	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	0	16	from	Activation	44:53	arg1	Cells					71:75	Pancreatic β Cells	58:75	Pancreatic β Cells	58:75	O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells.
31164864	6	17	theme	high	1058:1061	arg1	concentrations					1071:1084	high glucose concentrations	1058:1084	high glucose concentrations in β cell lines	1058:1100	Our study shows that TxNIP is subjected to O-GlcNAcylation in response to high glucose concentrations in β cell lines.
31164864	2	18	theme	scaffold	240:247	arg1	TxNIP					229:233	TxNIP	229:233	TxNIP	229:233	TxNIP is a scaffold protein interacting with target proteins to inhibit or stimulate their activity.
31164864	2	18	theme	scaffold	240:247	arg1	protein					249:255	a scaffold protein	238:255	a scaffold protein interacting with target proteins	238:288	TxNIP is a scaffold protein interacting with target proteins to inhibit or stimulate their activity.
31164864	3	19	theme	protein	430:436	arg1	NLRP3					438:442	the inflammasome protein NLRP3	413:442	the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3)	413:482	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	9	20	theme	inflammasome	1488:1499	arg1	activation					1501:1510	inflammasome activation	1488:1510	inflammasome activation	1488:1510	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	9	21	from	induction	1414:1422	arg1	islets					1472:1477	human and rat islets	1458:1477	human and rat islets	1458:1477	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	9	22	theme	enhanced	1528:1535	arg1	IL1β					1545:1548	enhanced cleaved IL1β	1528:1548	enhanced cleaved IL1β	1528:1548	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	1	23	theme	interacting	90:100	arg1	protein					102:108	Thioredoxin interacting protein	78:108	Thioredoxin interacting protein (TxNIP)	78:116	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	1	23	theme	interacting	90:100	arg1	TxNIP					111:115	TxNIP	111:115	TxNIP	111:115	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	7	24	theme	TxNIP	1229:1233	arg1	O-GlcNAcylation					1235:1249	TxNIP O-GlcNAcylation	1229:1249	TxNIP O-GlcNAcylation in INS1 832/13 cells	1229:1270	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	9	25	theme	human	1458:1462	arg1	islets					1472:1477	human and rat islets	1458:1477	human and rat islets	1458:1477	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	5	26	theme	proteins	786:793	arg1	O-GlcNAcylation					767:781	O-GlcNAcylation	767:781	O-GlcNAcylation of proteins	767:793	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	8	27	gly	O-GlcNAcylation	1303:1317	arg1	islets					1356:1361	islets	1356:1361	islets of diabetic rodents	1356:1381	Interestingly, expression and O-GlcNAcylation of TxNIP appeared to be increased in islets of diabetic rodents.
31164864	7	28	from	O-GlcNAcylation	1235:1249	arg1	cells					1266:1270	INS1 832/13 cells	1254:1270	INS1 832/13 cells	1254:1270	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	3	29	theme	pancreatic	532:541	arg1	cells					545:549	pancreatic β cells	532:549	pancreatic β cells	532:549	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	4	30	from	glucose	600:606	arg1	cells					624:628	pancreatic β cells	611:628	pancreatic β cells	611:628	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	4	31	theme	β	622:622	arg1	cells					624:628	pancreatic β cells	611:628	pancreatic β cells	611:628	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	10	32	theme	TxNIP	1659:1663	arg1	O-GlcNAcylation					1665:1679	TxNIP O-GlcNAcylation	1659:1679	TxNIP O-GlcNAcylation	1659:1679	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
31164864	10	33	theme	NLRP3	1625:1629	arg1	interaction					1631:1641	NLRP3 interaction	1625:1641	NLRP3 interaction	1625:1641	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
31164864	6	34	theme	β	1089:1089	arg1	lines					1096:1100	β cell lines	1089:1100	β cell lines	1089:1100	Our study shows that TxNIP is subjected to O-GlcNAcylation in response to high glucose concentrations in β cell lines.
31164864	3	35	theme	NLR	445:447	arg1	domain					463:468	pyrin domain containing 3	457:481	pyrin domain containing 3	457:481	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	35	theme	NLR	445:447	arg1	family					449:454	NLR family	445:454	NLR family	445:454	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	36	theme	high	359:362	arg1	glucose					364:370	high glucose	359:370	high glucose	359:370	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	9	37	theme	O-GlcNAcylation	1431:1445	arg1	pathway					1447:1453	the O-GlcNAcylation pathway	1427:1453	the O-GlcNAcylation pathway	1427:1453	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	11	38	theme	β	1857:1857	arg1	cells					1859:1863	β cells	1857:1863	β cells	1857:1863	Altogether, our study reveals that O-GlcNAcylation represents an important regulatory mechanism for TxNIP activity in β cells.
31164864	2	39	theme	target	274:279	arg1	proteins					281:288	target proteins	274:288	target proteins	274:288	TxNIP is a scaffold protein interacting with target proteins to inhibit or stimulate their activity.
31164864	9	40	theme	mechanistic	1391:1401	arg1	level					1403:1407	the mechanistic level	1387:1407	the mechanistic level	1387:1407	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	6	41	theme	cell	1091:1094	arg1	lines					1096:1100	β cell lines	1089:1100	β cell lines	1089:1100	Our study shows that TxNIP is subjected to O-GlcNAcylation in response to high glucose concentrations in β cell lines.
31164864	8	42	theme	TxNIP	1322:1326	arg1	O-GlcNAcylation					1303:1317	O-GlcNAcylation	1303:1317	O-GlcNAcylation	1303:1317	Interestingly, expression and O-GlcNAcylation of TxNIP appeared to be increased in islets of diabetic rodents.
31164864	8	42	theme	TxNIP	1322:1326	arg1	expression					1288:1297	expression	1288:1297	expression	1288:1297	Interestingly, expression and O-GlcNAcylation of TxNIP appeared to be increased in islets of diabetic rodents.
31164864	6	43	theme	glucose	1063:1069	arg1	concentrations					1071:1084	high glucose concentrations	1058:1084	high glucose concentrations in β cell lines	1058:1100	Our study shows that TxNIP is subjected to O-GlcNAcylation in response to high glucose concentrations in β cell lines.
31164864	3	44	theme	β	510:510	arg1	secretion					519:527	interleukin-1 β (IL1β) secretion	496:527	interleukin-1 β (IL1β) secretion	496:527	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	5	45	from	residues	910:917	arg1	proteins					929:936	target proteins	922:936	target proteins	922:936	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	7	46	theme	INS1	1254:1257	arg1	cells					1266:1270	INS1 832/13 cells	1254:1270	INS1 832/13 cells	1254:1270	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	0	47	theme	Inflammasome	31:42	arg1	Activation					44:53	Inflammasome Activation	31:53	Inflammasome Activation in Pancreatic β Cells	31:75	O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells.
31164864	11	48	theme	TxNIP	1839:1843	arg1	activity					1845:1852	TxNIP activity	1839:1852	TxNIP activity in β cells	1839:1863	Altogether, our study reveals that O-GlcNAcylation represents an important regulatory mechanism for TxNIP activity in β cells.
31164864	3	49	theme	TxNIP	402:406	arg1	interaction					387:397	the interaction	383:397	the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3)	383:482	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	10	50	theme	OGT	1569:1571	arg1	Overexpression					1551:1564	Overexpression	1551:1564	Overexpression of OGT in HEK293 or INS1 832/13 cells	1551:1602	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
31164864	1	51	theme	glucotoxicity	192:204	arg1	mediator					180:187	a central mediator	170:187	a central mediator of glucotoxicity in pancreatic β cells	170:226	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	0	52	theme	Pancreatic	58:67	arg1	Cells					71:75	Pancreatic β Cells	58:75	Pancreatic β Cells	58:75	O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells.
31164864	9	53	theme	cleaved	1537:1543	arg1	IL1β					1545:1548	enhanced cleaved IL1β	1528:1548	enhanced cleaved IL1β	1528:1548	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	7	54	theme	OGA	1178:1180	arg1	expression					1182:1191	OGA expression	1178:1191	OGA expression	1178:1191	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	3	55	theme	β	543:543	arg1	cells					545:549	pancreatic β cells	532:549	pancreatic β cells	532:549	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	10	56	theme	OGA	1689:1691	arg1	overexpression					1693:1706	OGA overexpression	1689:1706	OGA overexpression	1689:1706	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
31164864	9	57	theme	rat	1468:1470	arg1	islets					1472:1477	human and rat islets	1458:1477	human and rat islets	1458:1477	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	8	58	theme	rodents	1375:1381	arg1	islets					1356:1361	islets	1356:1361	islets of diabetic rodents	1356:1381	Interestingly, expression and O-GlcNAcylation of TxNIP appeared to be increased in islets of diabetic rodents.
31164864	7	59	theme	pathway	1139:1145	arg1	Modification					1103:1114	Modification	1103:1114	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity	1103:1203	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	8	60	theme	diabetic	1366:1373	arg1	rodents					1375:1381	diabetic rodents	1366:1381	diabetic rodents	1366:1381	Interestingly, expression and O-GlcNAcylation of TxNIP appeared to be increased in islets of diabetic rodents.
31164864	6	61	from	concentrations	1071:1084	arg1	lines					1096:1100	β cell lines	1089:1100	β cell lines	1089:1100	Our study shows that TxNIP is subjected to O-GlcNAcylation in response to high glucose concentrations in β cell lines.
31164864	3	62	theme	containing	470:479	arg1	domain					463:468	pyrin domain containing 3	457:481	pyrin domain containing 3	457:481	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	62	theme	containing	470:479	arg1	family					449:454	NLR family	445:454	NLR family	445:454	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	5	63	dep	enzymes	816:822	arg1	OGA					960:962	OGA	960:962	OGA	960:962	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	5	63	dep	enzymes	816:822	arg1	enzymes					816:822	two enzymes	812:822	two enzymes	812:822	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	5	63	dep	enzymes	816:822	arg1	O-GlcNAcase					947:957	the O-GlcNAcase	943:957	the O-GlcNAcase (OGA)	943:963	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	5	63	dep	enzymes	816:822	arg1	transferase					838:848	the O-GlcNAc transferase	825:848	the O-GlcNAc transferase (OGT)	825:854	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	5	63	dep	enzymes	816:822	arg1	OGT					851:853	OGT	851:853	OGT	851:853	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	3	64	dep	NLRP3	438:442	arg1	domain					463:468	pyrin domain containing 3	457:481	pyrin domain containing 3	457:481	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	64	dep	NLRP3	438:442	arg1	family					449:454	NLR family	445:454	NLR family	445:454	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	1	65	from	mediator	180:187	arg1	cells					222:226	pancreatic β cells	209:226	pancreatic β cells	209:226	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	4	66	theme	β-N-acetylglucosamine	675:695	arg1	implication					651:661	the implication	647:661	the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level	647:764	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	1	67	theme	Thioredoxin	78:88	arg1	protein					102:108	Thioredoxin interacting protein	78:108	Thioredoxin interacting protein (TxNIP)	78:116	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	1	67	theme	Thioredoxin	78:88	arg1	TxNIP					111:115	TxNIP	111:115	TxNIP	111:115	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	10	68	from	Overexpression	1551:1564	arg1	cells					1598:1602	HEK293 or INS1 832/13 cells	1576:1602	HEK293 or INS1 832/13 cells	1576:1602	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
31164864	4	69	theme	posttranslational	742:758	arg1	level					760:764	the posttranslational level	738:764	the posttranslational level	738:764	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	6	70	from	O-GlcNAcylation	1027:1041	arg1	response					1046:1053	response	1046:1053	response to high glucose concentrations in β cell lines	1046:1100	Our study shows that TxNIP is subjected to O-GlcNAcylation in response to high glucose concentrations in β cell lines.
31164864	3	71	theme	pyrin	457:461	arg1	domain					463:468	pyrin domain containing 3	457:481	pyrin domain containing 3	457:481	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	3	71	theme	pyrin	457:461	arg1	family					449:454	NLR family	445:454	NLR family	445:454	Recent studies reported that high glucose stimulates the interaction of TxNIP with the inflammasome protein NLRP3 (NLR family, pyrin domain containing 3) to increase interleukin-1 β (IL1β) secretion by pancreatic β cells.
31164864	1	72	theme	pancreatic	209:218	arg1	cells					222:226	pancreatic β cells	209:226	pancreatic β cells	209:226	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	9	73	theme	pathway	1447:1453	arg1	induction					1414:1422	the induction	1410:1422	the induction of the O-GlcNAcylation pathway in human and rat islets	1410:1477	At the mechanistic level, the induction of the O-GlcNAcylation pathway in human and rat islets promotes inflammasome activation as evidenced by enhanced cleaved IL1β.
31164864	7	74	theme	832/13	1259:1264	arg1	cells					1266:1270	INS1 832/13 cells	1254:1270	INS1 832/13 cells	1254:1270	Modification of the O-GlcNAcylation pathway through manipulation of OGT or OGA expression or activity significantly modulates TxNIP O-GlcNAcylation in INS1 832/13 cells.
31164864	1	75	theme	central	172:178	arg1	mediator					180:187	a central mediator	170:187	a central mediator of glucotoxicity in pancreatic β cells	170:226	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	5	76	theme	target	922:927	arg1	proteins					929:936	target proteins	922:936	target proteins	922:936	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	5	77	theme	O-GlcNAc	829:836	arg1	enzymes					816:822	two enzymes	812:822	two enzymes	812:822	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	5	77	theme	O-GlcNAc	829:836	arg1	OGT					851:853	OGT	851:853	OGT	851:853	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	5	77	theme	O-GlcNAc	829:836	arg1	transferase					838:848	the O-GlcNAc transferase	825:848	the O-GlcNAc transferase (OGT)	825:854	O-GlcNAcylation of proteins is controlled by two enzymes: the O-GlcNAc transferase (OGT), which transfers a monosaccharide to serine/threonine residues on target proteins, and the O-GlcNAcase (OGA), which removes it.
31164864	1	78	theme	β	220:220	arg1	cells					222:226	pancreatic β cells	209:226	pancreatic β cells	209:226	Thioredoxin interacting protein (TxNIP), which strongly responds to glucose, has emerged as a central mediator of glucotoxicity in pancreatic β cells.
31164864	0	79	theme	β	69:69	arg1	Cells					71:75	Pancreatic β Cells	58:75	Pancreatic β Cells	58:75	O-GlcNacylation Links TxNIP to Inflammasome Activation in Pancreatic β Cells.
31164864	4	80	theme	TxNIP	591:595	arg1	regulation					577:586	the regulation	573:586	the regulation of TxNIP by glucose in pancreatic β cells	573:628	To better understand the regulation of TxNIP by glucose in pancreatic β cells, we investigated the implication of O-linked β-N-acetylglucosamine (O-GlcNAcylation) in regulating TxNIP at the posttranslational level.
31164864	10	81	theme	HEK293	1576:1581	arg1	cells					1598:1602	HEK293 or INS1 832/13 cells	1576:1602	HEK293 or INS1 832/13 cells	1576:1602	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
31164864	10	82	theme	832/13	1591:1596	arg1	cells					1598:1602	HEK293 or INS1 832/13 cells	1576:1602	HEK293 or INS1 832/13 cells	1576:1602	Overexpression of OGT in HEK293 or INS1 832/13 cells stimulates TxNIP and NLRP3 interaction, while reducing TxNIP O-GlcNAcylation through OGA overexpression destabilizes this interaction.
30459710	0	0	theme	Candidate	79:87	arg1	O-GlcNAcylation					49:63	Dynamic O-GlcNAcylation	41:63	Dynamic O-GlcNAcylation of COPγ1	41:72	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	0	0	theme	Candidate	79:87	arg1	Regulator					89:97	a Candidate Regulator	77:97	a Candidate Regulator of Protein Trafficking	77:120	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	7	1	theme	protein	1255:1261	arg1	pathways					1275:1282	mammalian protein trafficking pathways	1245:1282	mammalian protein trafficking pathways	1245:1282	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	11	2	theme	biological	1911:1920	arg1	contexts					1922:1929	biological contexts	1911:1929	biological contexts	1911:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	4	3	theme	small	689:693	arg1	subset					695:700	only a small subset	682:700	only a small subset of these	682:709	However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress.
30459710	11	4	from	studies	1878:1884	arg1	host					1903:1906	a host	1901:1906	a host of biological contexts	1901:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	7	5	theme	trafficking	1263:1273	arg1	pathways					1275:1282	mammalian protein trafficking pathways	1245:1282	mammalian protein trafficking pathways	1245:1282	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	10	6	theme	analogous	1690:1698	arg1	system					1682:1687	the mammalian COPI system	1663:1687	the mammalian COPI system	1663:1687	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	5	7	from	challenge	906:914	arg1	field					923:927	the field	919:927	the field	919:927	Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field.
30459710	6	8	theme	O-GlcNAcylated	1110:1123	arg1	proteins					1125:1132	O-GlcNAcylated proteins	1110:1132	O-GlcNAcylated proteins	1110:1132	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	10	9	theme	other	1736:1740	arg1	pathways					1762:1769	other protein trafficking pathways	1736:1769	other protein trafficking pathways	1736:1769	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	5	10	theme	significant	894:904	arg1	challenge					906:914	a significant challenge	892:914	a significant challenge in the field	892:927	Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field.
30459710	7	11	theme	proof-of-principle	1138:1155	arg1	experiments					1157:1167	proof-of-principle experiments	1138:1167	proof-of-principle experiments	1138:1167	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	3	12	theme	identifying	531:541	arg1	thousands					543:551	identifying thousands	531:551	identifying thousands of its substrates	531:569	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	6	13	theme	quantitative	986:997	arg1	spectrometry					1004:1015	quantitative mass spectrometry	986:1015	quantitative mass spectrometry	986:1015	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	4	14	theme	glycosylation	724:736	arg1	status					738:743	their glycosylation status	718:743	their glycosylation status	718:743	However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress.
30459710	8	15	theme	protein	1390:1396	arg1	complex					1407:1413	the coat protein I (COPI) complex	1381:1413	the coat protein I (COPI) complex	1381:1413	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	2	16	theme	O-GlcNAcylation	289:303	arg1	dysregulation					272:284	dysregulation	272:284	dysregulation of O-GlcNAcylation	272:303	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	4	17	theme	O-GlcNAcylated	638:651	arg1	proteins					653:660	many O-GlcNAcylated proteins	633:660	many O-GlcNAcylated proteins	633:660	However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress.
30459710	0	18	theme	Trafficking	110:120	arg1	O-GlcNAcylation					49:63	Dynamic O-GlcNAcylation	41:63	Dynamic O-GlcNAcylation of COPγ1	41:72	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	0	18	theme	Trafficking	110:120	arg1	Regulator					89:97	a Candidate Regulator	77:97	a Candidate Regulator of Protein Trafficking	77:120	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	6	19	from	changes	1099:1105	arg1	proteins					1125:1132	O-GlcNAcylated proteins	1110:1132	O-GlcNAcylated proteins	1110:1132	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	4	20	theme	typical	762:768	arg1	stimulus					770:777	a typical stimulus	760:777	a typical stimulus	760:777	However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress.
30459710	6	21	theme	stimulus-dependent	1080:1097	arg1	changes					1099:1105	stimulus-dependent changes	1080:1105	stimulus-dependent changes in O-GlcNAcylated proteins	1080:1132	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	1	22	theme	abundant	171:178	arg1	β-N-acetylglucosamine					132:152	O-linked β-N-acetylglucosamine	123:152	O-linked β-N-acetylglucosamine (O-GlcNAc)	123:163	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	22	theme	abundant	171:178	arg1	form					208:211	an abundant and essential intracellular form	168:211	an abundant and essential intracellular form of protein glycosylation in animals and plants	168:258	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	0	23	theme	Protein	102:108	arg1	Trafficking					110:120	Protein Trafficking	102:120	Protein Trafficking	102:120	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	7	24	from	changes	1211:1217	arg1	pathways					1275:1282	mammalian protein trafficking pathways	1245:1282	mammalian protein trafficking pathways	1245:1282	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	7	24	from	changes	1211:1217	arg1	substrates					1231:1240	O-GlcNAc substrates	1222:1240	O-GlcNAc substrates	1222:1240	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	7	25	theme	new	1183:1185	arg1	workflow					1187:1194	this new workflow	1178:1194	this new workflow	1178:1194	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	11	26	from	O-GlcNAc	1889:1896	arg1	host					1903:1906	a host	1901:1906	a host of biological contexts	1901:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	9	27	theme	COPI	1591:1594	arg1	trafficking					1596:1606	COPI trafficking	1591:1606	COPI trafficking	1591:1606	Moreover, we detected 11 O-GlcNAc moieties on COPγ1 and found that this modification is reduced by a model secretory stress that halts COPI trafficking.
30459710	11	28	theme	myriad	1832:1837	arg1	systems					1839:1845	myriad systems	1832:1845	myriad systems	1832:1845	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	11	28	theme	myriad	1832:1837	arg1	studies					1878:1884	empowering future studies	1860:1884	empowering future studies of O-GlcNAc in a host of biological contexts	1860:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	5	29	theme	signaling	866:874	arg1	context					876:882	any given signaling context	856:882	any given signaling context	856:882	Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field.
30459710	0	30	theme	Novel	2:6	arg1	Workflow					24:31	A Novel Glycoproteomics Workflow	0:31	A Novel Glycoproteomics Workflow	0:31	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	9	31	theme	model	1557:1561	arg1	stress					1573:1578	a model secretory stress	1555:1578	a model secretory stress that halts COPI trafficking	1555:1606	Moreover, we detected 11 O-GlcNAc moieties on COPγ1 and found that this modification is reduced by a model secretory stress that halts COPI trafficking.
30459710	3	32	theme	substrates	560:569	arg1	thousands					543:551	identifying thousands	531:551	identifying thousands of its substrates	531:569	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	1	33	theme	essential	184:192	arg1	β-N-acetylglucosamine					132:152	O-linked β-N-acetylglucosamine	123:152	O-linked β-N-acetylglucosamine (O-GlcNAc)	123:163	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	33	theme	essential	184:192	arg1	form					208:211	an abundant and essential intracellular form	168:211	an abundant and essential intracellular form of protein glycosylation in animals and plants	168:258	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	11	34	theme	contexts	1922:1929	arg1	host					1903:1906	a host	1901:1906	a host of biological contexts	1901:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	2	35	theme	wide	317:320	arg1	diabetes					359:366	diabetes	359:366	diabetes	359:366	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	2	35	theme	wide	317:320	arg1	neurodegeneration					373:389	neurodegeneration	373:389	neurodegeneration	373:389	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	2	35	theme	wide	317:320	arg1	cancer					351:356	cancer	351:356	cancer	351:356	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	2	35	theme	wide	317:320	arg1	range					322:326	a wide range	315:326	a wide range of diseases, including cancer, diabetes, and neurodegeneration	315:389	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	1	36	theme	intracellular	194:206	arg1	β-N-acetylglucosamine					132:152	O-linked β-N-acetylglucosamine	123:152	O-linked β-N-acetylglucosamine (O-GlcNAc)	123:163	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	36	theme	intracellular	194:206	arg1	form					208:211	an abundant and essential intracellular form	168:211	an abundant and essential intracellular form of protein glycosylation in animals and plants	168:258	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	6	37	theme	chemical	965:972	arg1	biology					974:980	chemical biology	965:980	chemical biology	965:980	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	11	38	from	host	1903:1906	arg1	systems					1839:1845	myriad systems	1832:1845	myriad systems	1832:1845	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	11	38	from	host	1903:1906	arg1	studies					1878:1884	empowering future studies	1860:1884	empowering future studies of O-GlcNAc in a host of biological contexts	1860:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	6	39	theme	glycoproteomics	1041:1055	arg1	workflow					1057:1064	a new glycoproteomics workflow	1035:1064	a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins	1035:1132	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	5	40	theme	O-GlcNAcylation	829:843	arg1	changes					845:851	the functionally important O-GlcNAcylation changes	802:851	the functionally important O-GlcNAcylation changes in any given signaling context	802:882	Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field.
30459710	0	41	theme	Glycoproteomics	8:22	arg1	Workflow					24:31	A Novel Glycoproteomics Workflow	0:31	A Novel Glycoproteomics Workflow	0:31	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	8	42	theme	COPI	1401:1404	arg1	complex					1407:1413	the coat protein I (COPI) complex	1381:1413	the coat protein I (COPI) complex	1381:1413	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	8	43	theme	complex	1407:1413	arg1	COPγ1					1348:1352	COPγ1	1348:1352	COPγ1	1348:1352	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	8	43	theme	complex	1407:1413	arg1	component					1368:1376	an essential component	1355:1376	an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking	1355:1453	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	9	44	theme	secretory	1563:1571	arg1	stress					1573:1578	a model secretory stress	1555:1578	a model secretory stress that halts COPI trafficking	1555:1606	Moreover, we detected 11 O-GlcNAc moieties on COPγ1 and found that this modification is reduced by a model secretory stress that halts COPI trafficking.
30459710	10	45	theme	reported	1718:1725	arg1	roles					1727:1731	its previously reported roles	1703:1731	its previously reported roles in other protein trafficking pathways	1703:1769	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	0	46	theme	Dynamic	41:47	arg1	O-GlcNAcylation					49:63	Dynamic O-GlcNAcylation	41:63	Dynamic O-GlcNAcylation of COPγ1	41:72	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	0	46	theme	Dynamic	41:47	arg1	Regulator					89:97	a Candidate Regulator	77:97	a Candidate Regulator of Protein Trafficking	77:120	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	3	47	theme	central	482:488	arg1	thousands					543:551	identifying thousands	531:551	identifying thousands of its substrates	531:569	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	3	47	theme	central	482:488	arg1	aspects					490:496	central aspects	482:496	central aspects	482:496	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	3	48	theme	great	436:440	arg1	strides					442:448	great strides	436:448	great strides	436:448	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	8	49	theme	protein	1435:1441	arg1	trafficking					1443:1453	Golgi protein trafficking	1429:1453	Golgi protein trafficking	1429:1453	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	1	50	theme	protein	216:222	arg1	glycosylation					224:236	protein glycosylation	216:236	protein glycosylation	216:236	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	5	51	theme	given	860:864	arg1	context					876:882	any given signaling context	856:882	any given signaling context	856:882	Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field.
30459710	6	52	theme	mass	999:1002	arg1	spectrometry					1004:1015	quantitative mass spectrometry	986:1015	quantitative mass spectrometry	986:1015	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	11	53	theme	O-GlcNAc	1889:1896	arg1	systems					1839:1845	myriad systems	1832:1845	myriad systems	1832:1845	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	11	53	theme	O-GlcNAc	1889:1896	arg1	studies					1878:1884	empowering future studies	1860:1884	empowering future studies of O-GlcNAc in a host of biological contexts	1860:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	8	54	theme	Golgi	1429:1433	arg1	trafficking					1443:1453	Golgi protein trafficking	1429:1453	Golgi protein trafficking	1429:1453	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	1	55	theme	glycosylation	224:236	arg1	β-N-acetylglucosamine					132:152	O-linked β-N-acetylglucosamine	123:152	O-linked β-N-acetylglucosamine (O-GlcNAc)	123:163	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	55	theme	glycosylation	224:236	arg1	form					208:211	an abundant and essential intracellular form	168:211	an abundant and essential intracellular form of protein glycosylation in animals and plants	168:258	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	6	56	theme	new	1037:1039	arg1	workflow					1057:1064	a new glycoproteomics workflow	1035:1064	a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins	1035:1132	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	10	57	theme	trafficking	1750:1760	arg1	pathways					1762:1769	other protein trafficking pathways	1736:1769	other protein trafficking pathways	1736:1769	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	11	58	theme	empowering	1860:1869	arg1	systems					1839:1845	myriad systems	1832:1845	myriad systems	1832:1845	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	11	58	theme	empowering	1860:1869	arg1	studies					1878:1884	empowering future studies	1860:1884	empowering future studies of O-GlcNAc in a host of biological contexts	1860:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	7	59	used	used	1173:1176	arg2	we					1170:1171	we	1170:1171	we	1170:1171	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	10	60	theme	protein	1742:1748	arg1	pathways					1762:1769	other protein trafficking pathways	1736:1769	other protein trafficking pathways	1736:1769	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	1	61	from	form	208:211	arg1	plants					253:258	plants	253:258	plants	253:258	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	61	from	form	208:211	arg1	animals					241:247	animals	241:247	animals	241:247	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	62	theme	O-linked	123:130	arg1	β-N-acetylglucosamine					132:152	O-linked β-N-acetylglucosamine	123:152	O-linked β-N-acetylglucosamine (O-GlcNAc)	123:163	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	62	theme	O-linked	123:130	arg1	form					208:211	an abundant and essential intracellular form	168:211	an abundant and essential intracellular form of protein glycosylation in animals and plants	168:258	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	62	theme	O-linked	123:130	arg1	O-GlcNAc					155:162	O-GlcNAc	155:162	O-GlcNAc	155:162	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	11	63	theme	future	1871:1876	arg1	systems					1839:1845	myriad systems	1832:1845	myriad systems	1832:1845	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	11	63	theme	future	1871:1876	arg1	studies					1878:1884	empowering future studies	1860:1884	empowering future studies of O-GlcNAc in a host of biological contexts	1860:1929	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	10	64	theme	COPI	1677:1680	arg1	system					1682:1687	the mammalian COPI system	1663:1687	the mammalian COPI system	1663:1687	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	5	65	from	changes	845:851	arg1	context					876:882	any given signaling context	856:882	any given signaling context	856:882	Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field.
30459710	2	66	theme	diseases	331:338	arg1	diabetes					359:366	diabetes	359:366	diabetes	359:366	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	2	66	theme	diseases	331:338	arg1	neurodegeneration					373:389	neurodegeneration	373:389	neurodegeneration	373:389	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	2	66	theme	diseases	331:338	arg1	cancer					351:356	cancer	351:356	cancer	351:356	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	2	66	theme	diseases	331:338	arg1	range					322:326	a wide range	315:326	a wide range of diseases, including cancer, diabetes, and neurodegeneration	315:389	In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration.
30459710	11	67	theme	glycoproteomics	1790:1804	arg1	workflow					1806:1813	our glycoproteomics workflow	1786:1813	our glycoproteomics workflow	1786:1813	More broadly, our glycoproteomics workflow is applicable to myriad systems and stimuli, empowering future studies of O-GlcNAc in a host of biological contexts.
30459710	1	68	link	O-linked	123:130	arg1	β-N-acetylglucosamine					132:152	O-linked β-N-acetylglucosamine	123:152	O-linked β-N-acetylglucosamine (O-GlcNAc)	123:163	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	68	link	O-linked	123:130	arg1	form					208:211	an abundant and essential intracellular form	168:211	an abundant and essential intracellular form of protein glycosylation in animals and plants	168:258	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	1	68	link	O-linked	123:130	arg1	O-GlcNAc					155:162	O-GlcNAc	155:162	O-GlcNAc	155:162	O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants.
30459710	6	69	dep	biology	974:980	arg1	methods					1017:1023	methods	1017:1023	methods	1017:1023	To address this need, we leveraged chemical biology and quantitative mass spectrometry methods to create a new glycoproteomics workflow for profiling stimulus-dependent changes in O-GlcNAcylated proteins.
30459710	4	70	theme	these	705:709	arg1	subset					695:700	only a small subset	682:700	only a small subset of these	682:709	However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress.
30459710	8	71	theme	coat	1385:1388	arg1	complex					1407:1413	the coat protein I (COPI) complex	1381:1413	the coat protein I (COPI) complex	1381:1413	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	8	72	theme	essential	1358:1366	arg1	COPγ1					1348:1352	COPγ1	1348:1352	COPγ1	1348:1352	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	8	72	theme	essential	1358:1366	arg1	component					1368:1376	an essential component	1355:1376	an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking	1355:1453	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	10	73	theme	mammalian	1667:1675	arg1	system					1682:1687	the mammalian COPI system	1663:1687	the mammalian COPI system	1663:1687	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	4	74	theme	many	633:636	arg1	proteins					653:660	many O-GlcNAcylated proteins	633:660	many O-GlcNAcylated proteins	633:660	However, while many O-GlcNAcylated proteins have been reported, only a small subset of these change their glycosylation status in response to a typical stimulus or stress.
30459710	8	75	theme	dynamic	1321:1327	arg1	O-GlcNAcylation					1329:1343	dynamic O-GlcNAcylation	1321:1343	dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking	1321:1453	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	3	76	theme	O-GlcNAc	501:508	arg1	signaling					510:518	O-GlcNAc signaling	501:518	O-GlcNAc signaling	501:518	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	9	77	theme	O-GlcNAc	1481:1488	arg1	moieties					1490:1497	11 O-GlcNAc moieties	1478:1497	11 O-GlcNAc moieties	1478:1497	Moreover, we detected 11 O-GlcNAc moieties on COPγ1 and found that this modification is reduced by a model secretory stress that halts COPI trafficking.
30459710	0	78	theme	COPγ1	68:72	arg1	O-GlcNAcylation					49:63	Dynamic O-GlcNAcylation	41:63	Dynamic O-GlcNAcylation of COPγ1	41:72	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	0	78	theme	COPγ1	68:72	arg1	Regulator					89:97	a Candidate Regulator	77:97	a Candidate Regulator of Protein Trafficking	77:120	A Novel Glycoproteomics Workflow Reveals Dynamic O-GlcNAcylation of COPγ1 as a Candidate Regulator of Protein Trafficking.
30459710	7	79	theme	O-GlcNAc	1222:1229	arg1	substrates					1231:1240	O-GlcNAc substrates	1222:1240	O-GlcNAc substrates	1222:1240	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30459710	5	80	theme	important	819:827	arg1	changes					845:851	the functionally important O-GlcNAcylation changes	802:851	the functionally important O-GlcNAcylation changes in any given signaling context	802:882	Identifying the functionally important O-GlcNAcylation changes in any given signaling context remains a significant challenge in the field.
30459710	10	81	from	roles	1727:1731	arg1	pathways					1762:1769	other protein trafficking pathways	1736:1769	other protein trafficking pathways	1736:1769	Our results suggest that O-GlcNAcylation may regulate the mammalian COPI system, analogous to its previously reported roles in other protein trafficking pathways.
30459710	3	82	theme	signaling	510:518	arg1	thousands					543:551	identifying thousands	531:551	identifying thousands of its substrates	531:569	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	3	82	theme	signaling	510:518	arg1	aspects					490:496	central aspects	482:496	central aspects	482:496	Since its discovery more than 30 years ago, great strides have been made in understanding central aspects of O-GlcNAc signaling, including identifying thousands of its substrates and characterizing the enzymes that govern it.
30459710	8	83	theme	COPγ1	1348:1352	arg1	O-GlcNAcylation					1329:1343	dynamic O-GlcNAcylation	1321:1343	dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking	1321:1453	Interestingly, our results revealed dynamic O-GlcNAcylation of COPγ1, an essential component of the coat protein I (COPI) complex that mediates Golgi protein trafficking.
30459710	7	84	theme	mammalian	1245:1253	arg1	pathways					1275:1282	mammalian protein trafficking pathways	1245:1282	mammalian protein trafficking pathways	1245:1282	In proof-of-principle experiments, we used this new workflow to interrogate changes in O-GlcNAc substrates in mammalian protein trafficking pathways.
30134155	3	0	theme	post-translational	331:348	arg1	sensor					409:414	a sensor	407:414	a sensor of cellular nutrients	407:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	0	theme	post-translational	331:348	arg1	β-N-acetylglucosamine					293:313	O-linked β-N-acetylglucosamine	284:313	O-linked β-N-acetylglucosamine (O-GlcNAc)	284:324	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	0	theme	post-translational	331:348	arg1	modification					350:361	a post-translational modification	329:361	a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients	329:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	0	1	theme	Caenorhabditis	80:93	arg1	elegans					95:101	Caenorhabditis elegans	80:101	Caenorhabditis elegans	80:101	O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans.
30134155	5	2	theme	O-GlcNAc	700:707	arg1	lack					692:695	A lack	690:695	A lack of O-GlcNAc	690:707	A lack of O-GlcNAc induces the AKT-1 branch in the insulin-signaling pathway to use glycolysis.
30134155	6	3	theme	pathway	878:884	arg1	branch					846:851	an opposing branch	834:851	an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function	834:981	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	6	4	theme	FOXO	914:917	arg1	DAF-16					940:945	the FOXO transcription factor DAF-16	910:945	the FOXO transcription factor DAF-16 to influence mitochondrial function	910:981	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	4	5	theme	O-GlcNAcase	620:630	arg1	disruptions					566:576	disruptions	566:576	disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively	566:687	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	6	6	theme	insulin-signaling	860:876	arg1	pathway					878:884	the insulin-signaling pathway	856:884	the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function	856:981	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	7	7	theme	metabolic	1036:1044	arg1	pathways					1046:1053	metabolic pathways	1036:1053	metabolic pathways	1036:1053	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	6	8	theme	mitochondrial	960:972	arg1	function					974:981	mitochondrial function	960:981	mitochondrial function	960:981	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	3	9	theme	threonines	378:387	arg1	sensor					409:414	a sensor	407:414	a sensor of cellular nutrients	407:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	9	theme	threonines	378:387	arg1	β-N-acetylglucosamine					293:313	O-linked β-N-acetylglucosamine	284:313	O-linked β-N-acetylglucosamine (O-GlcNAc)	284:324	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	9	theme	threonines	378:387	arg1	modification					350:361	a post-translational modification	329:361	a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients	329:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	0	10	from	Response	49:56	arg1	elegans					95:101	Caenorhabditis elegans	80:101	Caenorhabditis elegans	80:101	O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans.
30134155	7	11	theme	mechanism	1018:1026	arg1	existence					988:996	The existence	984:996	The existence of this toggle-like mechanism between metabolic pathways	984:1053	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	4	12	theme	neuronal	514:521	arg1	regeneration					523:534	neuronal regeneration	514:534	neuronal regeneration	514:534	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	7	13	theme	regenerative	1184:1195	arg1	response					1197:1204	the regenerative response	1180:1204	the regenerative response	1180:1204	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	6	14	theme	opposing	837:844	arg1	branch					846:851	an opposing branch	834:851	an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function	834:981	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	0	15	theme	O-GlcNAc	0:7	arg1	Signaling					9:17	O-GlcNAc Signaling	0:17	O-GlcNAc Signaling	0:17	O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans.
30134155	4	16	theme	transferase	601:611	arg1	disruptions					566:576	disruptions	566:576	disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively	566:687	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	5	17	dep	pathway	759:765	arg1	use					770:772	use	770:772	to use glycolysis	767:783	A lack of O-GlcNAc induces the AKT-1 branch in the insulin-signaling pathway to use glycolysis.
30134155	6	18	theme	factor	933:938	arg1	DAF-16					940:945	the FOXO transcription factor DAF-16	910:945	the FOXO transcription factor DAF-16 to influence mitochondrial function	910:981	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	4	19	theme	O-GlcNAc	592:599	arg1	transferase					601:611	the O-GlcNAc transferase	588:611	the O-GlcNAc transferase	588:611	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	5	20	theme	insulin-signaling	741:757	arg1	pathway					759:765	the insulin-signaling pathway	737:765	the insulin-signaling pathway to use glycolysis	737:783	A lack of O-GlcNAc induces the AKT-1 branch in the insulin-signaling pathway to use glycolysis.
30134155	7	21	theme	toggle-like	1006:1016	arg1	mechanism					1018:1026	this toggle-like mechanism	1001:1026	this toggle-like mechanism	1001:1026	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	7	22	theme	nutrient	1105:1112	arg1	status					1114:1119	cellular nutrient status	1096:1119	cellular nutrient status	1096:1119	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	4	23	theme	Caenorhabditis	477:490	arg1	elegans					492:498	Caenorhabditis elegans	477:498	Caenorhabditis elegans	477:498	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	0	24	theme	Regenerative	36:47	arg1	Response					49:56	the Regenerative Response	32:56	the Regenerative Response to Neuronal Injury in Caenorhabditis elegans	32:101	O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans.
30134155	3	25	theme	O-linked	284:291	arg1	β-N-acetylglucosamine					293:313	O-linked β-N-acetylglucosamine	284:313	O-linked β-N-acetylglucosamine (O-GlcNAc)	284:324	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	25	theme	O-linked	284:291	arg1	modification					350:361	a post-translational modification	329:361	a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients	329:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	25	theme	O-linked	284:291	arg1	O-GlcNAc					316:323	O-GlcNAc	316:323	O-GlcNAc	316:323	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	6	26	theme	transcription	919:931	arg1	DAF-16					940:945	the FOXO transcription factor DAF-16	910:945	the FOXO transcription factor DAF-16 to influence mitochondrial function	910:981	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	3	27	theme	cellular	419:426	arg1	nutrients					428:436	cellular nutrients	419:436	cellular nutrients	419:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	5	28	theme	AKT-1	721:725	arg1	branch					727:732	the AKT-1 branch	717:732	the AKT-1 branch	717:732	A lack of O-GlcNAc induces the AKT-1 branch in the insulin-signaling pathway to use glycolysis.
30134155	3	29	theme	serines	366:372	arg1	sensor					409:414	a sensor	407:414	a sensor of cellular nutrients	407:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	29	theme	serines	366:372	arg1	β-N-acetylglucosamine					293:313	O-linked β-N-acetylglucosamine	284:313	O-linked β-N-acetylglucosamine (O-GlcNAc)	284:324	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	29	theme	serines	366:372	arg1	modification					350:361	a post-translational modification	329:361	a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients	329:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	6	30	theme	O-GlcNAc	809:816	arg1	levels					818:823	increased O-GlcNAc levels	799:823	increased O-GlcNAc levels	799:823	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	1	31	theme	axon	119:122	arg1	Regrowth					104:111	Regrowth	104:111	Regrowth of an axon after injury	104:135	Regrowth of an axon after injury is an inherently metabolic undertaking.
30134155	1	31	theme	axon	119:122	arg1	metabolic					154:162	metabolic	154:162	metabolic	154:162	Regrowth of an axon after injury is an inherently metabolic undertaking.
30134155	3	32	theme	nutrients	428:436	arg1	sensor					409:414	a sensor	407:414	a sensor of cellular nutrients	407:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	32	theme	nutrients	428:436	arg1	modification					350:361	a post-translational modification	329:361	a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients	329:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	7	33	theme	damaged	1152:1158	arg1	neuron					1160:1165	a damaged neuron	1150:1165	a damaged neuron	1150:1165	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	4	34	theme	laser	458:462	arg1	axotomies					464:472	in vivo laser axotomies	450:472	in vivo laser axotomies	450:472	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	4	35	theme	in vivo	450:456	arg1	axotomies					464:472	in vivo laser axotomies	450:472	in vivo laser axotomies	450:472	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	6	36	theme	increased	799:807	arg1	levels					818:823	increased O-GlcNAc levels	799:823	increased O-GlcNAc levels	799:823	In contrast, increased O-GlcNAc levels activate an opposing branch of the insulin-signaling pathway whereby SGK-1 modulates the FOXO transcription factor DAF-16 to influence mitochondrial function.
30134155	2	37	theme	regulation	209:218	arg1	mechanisms					185:194	the mechanisms	181:194	the mechanisms of metabolic regulation that influence repair following injury	181:257	Yet the mechanisms of metabolic regulation that influence repair following injury are not well understood.
30134155	4	38	theme	O-GlcNAc	659:666	arg1	levels					668:673	O-GlcNAc levels	659:673	O-GlcNAc levels	659:673	Performing in vivo laser axotomies in Caenorhabditis elegans, we find that neuronal regeneration is substantially increased by disruptions of either the O-GlcNAc transferase or the O-GlcNAcase that decrease and increase O-GlcNAc levels, respectively.
30134155	2	39	theme	metabolic	199:207	arg1	regulation					209:218	metabolic regulation	199:218	metabolic regulation that influence repair following injury	199:257	Yet the mechanisms of metabolic regulation that influence repair following injury are not well understood.
30134155	7	40	from	metabolism	1136:1145	arg1	neuron					1160:1165	a damaged neuron	1150:1165	a damaged neuron	1150:1165	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	7	41	theme	cellular	1096:1103	arg1	status					1114:1119	cellular nutrient status	1096:1119	cellular nutrient status	1096:1119	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	0	42	theme	Neuronal	61:68	arg1	Injury					70:75	Neuronal Injury	61:75	Neuronal Injury	61:75	O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans.
30134155	7	43	theme	O-GlcNAc	1069:1076	arg1	signaling					1078:1086	O-GlcNAc signaling	1069:1086	O-GlcNAc signaling	1069:1086	The existence of this toggle-like mechanism between metabolic pathways suggests that O-GlcNAc signaling conveys cellular nutrient status to orchestrate metabolism in a damaged neuron and maximize the regenerative response.
30134155	3	44	link	O-linked	284:291	arg1	β-N-acetylglucosamine					293:313	O-linked β-N-acetylglucosamine	284:313	O-linked β-N-acetylglucosamine (O-GlcNAc)	284:324	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	44	link	O-linked	284:291	arg1	modification					350:361	a post-translational modification	329:361	a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients	329:436	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30134155	3	44	link	O-linked	284:291	arg1	O-GlcNAc					316:323	O-GlcNAc	316:323	O-GlcNAc	316:323	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serines and threonines that functions as a sensor of cellular nutrients.
30127386	0	0	theme	shock	71:75	arg1	response					77:84	heat shock response	66:84	heat shock response	66:84	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	5	1	theme	mRNAs	665:669	arg1	translation					643:653	the preferential translation	626:653	the preferential translation of stress mRNAs	626:669	Without O-GlcNAc modification, the preferential translation of stress mRNAs is impaired.
30127386	1	2	theme	ancient	119:125	arg1	pathway					137:143	an ancient signaling pathway	116:143	an ancient signaling pathway leading to thermoprotection of nearly all living organisms	116:202	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	1	2	theme	ancient	119:125	arg1	response					98:105	Heat shock response	87:105	Heat shock response (HSR)	87:111	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	0	3	theme	heat	66:69	arg1	response					77:84	heat shock response	66:84	heat shock response	66:84	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	4	4	theme	translation	498:508	arg1	factor					521:526	the key translation initiation factor	490:526	the key translation initiation factor eIF4GI	490:533	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	3	5	dep	Whether	376:382	arg1	regulates					414:422	regulates	414:422	regulates HSR	414:426	Whether and how O-GlcNAc modification regulates HSR remains unclear.
30127386	5	6	theme	O-GlcNAc	603:610	arg1	modification					612:623	O-GlcNAc modification	603:623	O-GlcNAc modification	603:623	Without O-GlcNAc modification, the preferential translation of stress mRNAs is impaired.
30127386	1	7	theme	signaling	127:135	arg1	pathway					137:143	an ancient signaling pathway	116:143	an ancient signaling pathway leading to thermoprotection of nearly all living organisms	116:202	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	1	7	theme	signaling	127:135	arg1	response					98:105	Heat shock response	87:105	Heat shock response (HSR)	87:111	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	4	8	theme	N-terminal	576:585	arg1	region					587:592	the N-terminal region	572:592	the N-terminal region	572:592	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	4	9	theme	key	494:496	arg1	factor					521:526	the key translation initiation factor	490:526	the key translation initiation factor eIF4GI	490:533	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	2	10	theme	reporting	332:340	arg1	fluctuations					362:373	reporting ambient temperature fluctuations	332:373	reporting ambient temperature fluctuations	332:373	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	7	11	theme	selective	972:980	arg1	translation					982:992	selective translation	972:992	selective translation	972:992	Mechanistically, we show that stress-induced eIF4GI O-GlcNAcylation repels poly(A)-binding protein 1 and promotes SG disassembly, thereby licensing stress mRNAs for selective translation.
30127386	2	12	link	O-linked	251:258	arg1	O-GlcNAc					283:290	O-GlcNAc	283:290	O-GlcNAc	283:290	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	2	12	link	O-linked	251:258	arg1	β-N-acetylglucosamine					260:280	intracellular O-linked β-N-acetylglucosamine	237:280	intracellular O-linked β-N-acetylglucosamine (O-GlcNAc)	237:291	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	2	12	link	O-linked	251:258	arg1	thermometer					316:326	a molecular 'thermometer'	303:327	a molecular 'thermometer' by reporting ambient temperature fluctuations	303:373	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	4	13	theme	heat	471:474	arg1	shock					476:480	heat shock	471:480	heat shock stress	471:487	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	7	14	theme	stress	955:960	arg1	mRNAs					962:966	licensing stress mRNAs	945:966	licensing stress mRNAs for selective translation	945:992	Mechanistically, we show that stress-induced eIF4GI O-GlcNAcylation repels poly(A)-binding protein 1 and promotes SG disassembly, thereby licensing stress mRNAs for selective translation.
30127386	2	15	theme	ambient	342:348	arg1	fluctuations					362:373	reporting ambient temperature fluctuations	332:373	reporting ambient temperature fluctuations	332:373	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	6	16	theme	stress	732:737	arg1	SGs					749:751	SGs	749:751	SGs	749:751	Unexpectedly, stress mRNAs are entrapped within stress granules (SGs) that are no longer dissolved during stress recovery.
30127386	6	16	theme	stress	732:737	arg1	granules					739:746	stress granules	732:746	stress granules (SGs) that are no longer dissolved during stress recovery	732:804	Unexpectedly, stress mRNAs are entrapped within stress granules (SGs) that are no longer dissolved during stress recovery.
30127386	8	17	theme	eIF4GI	1009:1014	arg1	mutants					1016:1022	various eIF4GI mutants	1001:1022	various eIF4GI mutants created by CRISPR/Cas9	1001:1045	Using various eIF4GI mutants created by CRISPR/Cas9, we demonstrate that eIF4GI acts as a translational switch via reversible O-GlcNAcylation.
30127386	7	18	theme	eIF4GI	852:857	arg1	O-GlcNAcylation					859:873	stress-induced eIF4GI O-GlcNAcylation	837:873	stress-induced eIF4GI O-GlcNAcylation	837:873	Mechanistically, we show that stress-induced eIF4GI O-GlcNAcylation repels poly(A)-binding protein 1 and promotes SG disassembly, thereby licensing stress mRNAs for selective translation.
30127386	5	19	theme	preferential	630:641	arg1	translation					643:653	the preferential translation	626:653	the preferential translation of stress mRNAs	626:669	Without O-GlcNAc modification, the preferential translation of stress mRNAs is impaired.
30127386	8	20	theme	various	1001:1007	arg1	mutants					1016:1022	various eIF4GI mutants	1001:1022	various eIF4GI mutants created by CRISPR/Cas9	1001:1045	Using various eIF4GI mutants created by CRISPR/Cas9, we demonstrate that eIF4GI acts as a translational switch via reversible O-GlcNAcylation.
30127386	9	21	theme	SG	1225:1226	arg1	dynamics					1228:1235	SG dynamics	1225:1235	SG dynamics	1225:1235	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	4	22	theme	shock	476:480	arg1	stress					482:487	heat shock stress	471:487	heat shock stress	471:487	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	6	23	theme	stress	790:795	arg1	recovery					797:804	stress recovery	790:804	stress recovery	790:804	Unexpectedly, stress mRNAs are entrapped within stress granules (SGs) that are no longer dissolved during stress recovery.
30127386	2	24	theme	molecular	305:313	arg1	β-N-acetylglucosamine					260:280	intracellular O-linked β-N-acetylglucosamine	237:280	intracellular O-linked β-N-acetylglucosamine (O-GlcNAc)	237:291	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	2	24	theme	molecular	305:313	arg1	thermometer					316:326	a molecular 'thermometer'	303:327	a molecular 'thermometer' by reporting ambient temperature fluctuations	303:373	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	0	25	theme	O-GlcNAc	0:7	arg1	switch					56:61	a translational switch	40:61	a translational switch in heat shock response	40:84	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	0	25	theme	O-GlcNAc	0:7	arg1	modification					9:20	O-GlcNAc modification	0:20	O-GlcNAc modification of eIF4GI	0:30	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	5	26	theme	stress	658:663	arg1	mRNAs					665:669	stress mRNAs	658:669	stress mRNAs	658:669	Without O-GlcNAc modification, the preferential translation of stress mRNAs is impaired.
30127386	7	27	theme	stress-induced	837:850	arg1	O-GlcNAcylation					859:873	stress-induced eIF4GI O-GlcNAcylation	837:873	stress-induced eIF4GI O-GlcNAcylation	837:873	Mechanistically, we show that stress-induced eIF4GI O-GlcNAcylation repels poly(A)-binding protein 1 and promotes SG disassembly, thereby licensing stress mRNAs for selective translation.
30127386	0	28	theme	eIF4GI	25:30	arg1	switch					56:61	a translational switch	40:61	a translational switch in heat shock response	40:84	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	0	28	theme	eIF4GI	25:30	arg1	modification					9:20	O-GlcNAc modification	0:20	O-GlcNAc modification of eIF4GI	0:30	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	4	29	theme	dynamic	545:551	arg1	O-GlcNAcylation					553:567	dynamic O-GlcNAcylation	545:567	dynamic O-GlcNAcylation	545:567	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	8	30	theme	translational	1085:1097	arg1	switch					1099:1104	a translational switch	1083:1104	a translational switch	1083:1104	Using various eIF4GI mutants created by CRISPR/Cas9, we demonstrate that eIF4GI acts as a translational switch via reversible O-GlcNAcylation.
30127386	8	30	theme	translational	1085:1097	arg1	eIF4GI					1068:1073	eIF4GI	1068:1073	eIF4GI	1068:1073	Using various eIF4GI mutants created by CRISPR/Cas9, we demonstrate that eIF4GI acts as a translational switch via reversible O-GlcNAcylation.
30127386	1	31	theme	Heat	87:90	arg1	HSR					108:110	HSR	108:110	HSR	108:110	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	1	31	theme	Heat	87:90	arg1	response					98:105	Heat shock response	87:105	Heat shock response (HSR)	87:111	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	1	31	theme	Heat	87:90	arg1	pathway					137:143	an ancient signaling pathway	116:143	an ancient signaling pathway leading to thermoprotection of nearly all living organisms	116:202	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	6	32	theme	stress	698:703	arg1	mRNAs					705:709	stress mRNAs	698:709	stress mRNAs	698:709	Unexpectedly, stress mRNAs are entrapped within stress granules (SGs) that are no longer dissolved during stress recovery.
30127386	9	33	theme	translational	1241:1253	arg1	reprogramming					1255:1267	translational reprogramming	1241:1267	translational reprogramming	1241:1267	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	1	34	theme	shock	92:96	arg1	HSR					108:110	HSR	108:110	HSR	108:110	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	1	34	theme	shock	92:96	arg1	response					98:105	Heat shock response	87:105	Heat shock response (HSR)	87:111	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	1	34	theme	shock	92:96	arg1	pathway					137:143	an ancient signaling pathway	116:143	an ancient signaling pathway leading to thermoprotection of nearly all living organisms	116:202	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	4	35	theme	factor	521:526	arg1	eIF4GI					528:533	the key translation initiation factor eIF4GI	490:533	the key translation initiation factor eIF4GI	490:533	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	2	36	theme	Emerging	205:212	arg1	evidence					214:221	Emerging evidence	205:221	Emerging evidence	205:221	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	1	37	theme	living	187:192	arg1	organisms					194:202	nearly all living organisms	176:202	nearly all living organisms	176:202	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	3	38	theme	O-GlcNAc	392:399	arg1	modification					401:412	O-GlcNAc modification	392:412	O-GlcNAc modification	392:412	Whether and how O-GlcNAc modification regulates HSR remains unclear.
30127386	4	39	theme	initiation	510:519	arg1	factor					521:526	the key translation initiation factor	490:526	the key translation initiation factor eIF4GI	490:533	Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region.
30127386	9	40	theme	protein	1205:1211	arg1	remodeling					1213:1222	protein remodeling	1205:1222	protein remodeling	1205:1222	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	0	41	from	switch	56:61	arg1	response					77:84	heat shock response	66:84	heat shock response	66:84	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	8	42	theme	reversible	1110:1119	arg1	O-GlcNAcylation					1121:1135	reversible O-GlcNAcylation	1110:1135	reversible O-GlcNAcylation	1110:1135	Using various eIF4GI mutants created by CRISPR/Cas9, we demonstrate that eIF4GI acts as a translational switch via reversible O-GlcNAcylation.
30127386	2	43	theme	O-linked	251:258	arg1	O-GlcNAc					283:290	O-GlcNAc	283:290	O-GlcNAc	283:290	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	2	43	theme	O-linked	251:258	arg1	β-N-acetylglucosamine					260:280	intracellular O-linked β-N-acetylglucosamine	237:280	intracellular O-linked β-N-acetylglucosamine (O-GlcNAc)	237:291	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	2	43	theme	O-linked	251:258	arg1	thermometer					316:326	a molecular 'thermometer'	303:327	a molecular 'thermometer' by reporting ambient temperature fluctuations	303:373	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	9	44	theme	central	1158:1164	arg1	mechanism					1166:1174	a central mechanism	1156:1174	a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming	1156:1267	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	9	45	dep	stress	1189:1194	arg1	sensing					1196:1202	sensing	1196:1202	sensing	1196:1202	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	9	45	dep	stress	1189:1194	arg1	remodeling					1213:1222	protein remodeling	1205:1222	protein remodeling	1205:1222	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	9	45	dep	stress	1189:1194	arg1	dynamics					1228:1235	SG dynamics	1225:1235	SG dynamics	1225:1235	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	9	45	dep	stress	1189:1194	arg1	reprogramming					1255:1267	translational reprogramming	1241:1267	translational reprogramming	1241:1267	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	1	46	theme	organisms	194:202	arg1	thermoprotection					156:171	thermoprotection	156:171	thermoprotection of nearly all living organisms	156:202	Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms.
30127386	2	47	theme	intracellular	237:249	arg1	O-GlcNAc					283:290	O-GlcNAc	283:290	O-GlcNAc	283:290	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	2	47	theme	intracellular	237:249	arg1	β-N-acetylglucosamine					260:280	intracellular O-linked β-N-acetylglucosamine	237:280	intracellular O-linked β-N-acetylglucosamine (O-GlcNAc)	237:291	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	2	47	theme	intracellular	237:249	arg1	thermometer					316:326	a molecular 'thermometer'	303:327	a molecular 'thermometer' by reporting ambient temperature fluctuations	303:373	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	7	48	theme	licensing	945:953	arg1	mRNAs					962:966	licensing stress mRNAs	945:966	licensing stress mRNAs for selective translation	945:992	Mechanistically, we show that stress-induced eIF4GI O-GlcNAcylation repels poly(A)-binding protein 1 and promotes SG disassembly, thereby licensing stress mRNAs for selective translation.
30127386	0	49	theme	translational	42:54	arg1	switch					56:61	a translational switch	40:61	a translational switch in heat shock response	40:84	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	0	49	theme	translational	42:54	arg1	modification					9:20	O-GlcNAc modification	0:20	O-GlcNAc modification of eIF4GI	0:30	O-GlcNAc modification of eIF4GI acts as a translational switch in heat shock response.
30127386	9	50	theme	heat	1184:1187	arg1	stress					1189:1194	heat stress sensing, protein remodeling, SG dynamics and translational reprogramming	1184:1267	heat stress sensing, protein remodeling, SG dynamics and translational reprogramming	1184:1267	Our study reveals a central mechanism linking heat stress sensing, protein remodeling, SG dynamics and translational reprogramming.
30127386	2	51	theme	temperature	350:360	arg1	fluctuations					362:373	reporting ambient temperature fluctuations	332:373	reporting ambient temperature fluctuations	332:373	Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations.
30127386	7	52	theme	-binding	889:896	arg1	protein					898:904	poly(A)-binding protein 1	882:906	poly(A)-binding protein 1	882:906	Mechanistically, we show that stress-induced eIF4GI O-GlcNAcylation repels poly(A)-binding protein 1 and promotes SG disassembly, thereby licensing stress mRNAs for selective translation.
29550419	4	0	dep	42°C	782:785	arg1	to					779:780	to	779:780	to	779:780	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	4	1	theme	Bioemulsifier	633:645	arg1	production					647:656	Bioemulsifier production	633:656	Bioemulsifier production	633:656	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	3	2	used	used	582:585	arg2	supernatant					566:576	JHT2 culture supernatant	553:576	JHT2 culture supernatant	553:576	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	6	3	theme	pyruvic	1348:1354	arg1	substitution					1368:1379	a pyruvic acid acetal substitution	1346:1379	a pyruvic acid acetal substitution at O-4 and O-6	1346:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	1	4	theme	food	270:273	arg1	processing					275:284	food processing	270:284	food processing	270:284	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	6	5	from	O-6	1392:1394	arg1	substitution					1368:1379	a pyruvic acid acetal substitution	1346:1379	a pyruvic acid acetal substitution at O-4 and O-6	1346:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	5	6	theme	typical	1021:1027	arg1	characteristics					1029:1043	typical characteristics	1021:1043	typical characteristics of exopolysaccharides (EPS)	1021:1071	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	6	7	link	3-O-linked	1310:1319	arg1	galactopyranosyl					1321:1336	3-O-linked galactopyranosyl	1310:1336	3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6	1310:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	5	8	theme	-β-D-galactopyranosyl	1135:1155	arg1	backbone					1089:1096	a backbone	1087:1096	a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	1087:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	7	9	theme	Ensifer	1443:1449	arg1	JHT2					1461:1464	Ensifer adhaerens JHT2	1443:1464	Ensifer adhaerens JHT2	1443:1464	Our results indicate that the EPS produced by Ensifer adhaerens JHT2 is a promising option for improving and maintaining stable emulsions in food prepared with edible oils.
29550419	5	10	theme	trypticase	875:884	arg1	broth					890:894	trypticase soy broth	875:894	trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	875:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	6	11	from	O-4	1384:1386	arg1	substitution					1368:1379	a pyruvic acid acetal substitution	1346:1379	a pyruvic acid acetal substitution at O-4 and O-6	1346:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	3	12	theme	highest	501:507	arg1	EI					531:532	EI	531:532	EI	531:532	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	3	12	theme	highest	501:507	arg1	index					524:528	the highest emulsification index	497:528	the highest emulsification index (EI)	497:533	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	4	13	theme	culture	683:689	arg1	media					691:695	nine culture media	678:695	nine culture media	678:695	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	3	14	dep	soy	459:461	arg1	oils					474:477	oils	474:477	oils	474:477	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	5	15	dep	pH6-7	922:926	arg1	revealed					1012:1019	revealed	1012:1019	revealed	1012:1019	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	3	16	theme	emulsification	509:522	arg1	EI					531:532	EI	531:532	EI	531:532	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	3	16	theme	emulsification	509:522	arg1	index					524:528	the highest emulsification index	497:528	the highest emulsification index (EI)	497:533	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	3	17	theme	soy	459:461	arg1	Emulsification					441:454	Emulsification	441:454	Emulsification of soy and canola oils	441:477	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	5	18	theme	bioemulsifier	981:993	arg1	Characterization					957:972	28-37°C. Characterization	948:972	28-37°C. Characterization of the bioemulsifier produced by JHT2	948:1010	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	19	theme	JHT2	861:864	arg1	supernatants					845:856	the supernatants	841:856	the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	841:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	20	from	O-2	1239:1241	arg1	structure					1226:1234	the structure	1222:1234	the structure at O-2	1222:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	1	21	theme	oil-in-water	181:192	arg1	emulsions					194:202	oil-in-water emulsions	181:202	oil-in-water emulsions	181:202	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	5	22	theme	1→4	1102:1104	arg1	-β-d-glucopyranosyl					1106:1124	(1→4)-β-d-glucopyranosyl	1101:1124	(1→4)-β-d-glucopyranosyl	1101:1124	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	23	dep	-β-D-galactopyranosyl	1135:1155	arg1	1→3					1131:1133	1→3	1131:1133	1→3	1131:1133	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	4	24	dep	10	754:755	arg1	to					751:752	to	751:752	to	751:752	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	7	25	theme	edible	1557:1562	arg1	oils					1564:1567	edible oils	1557:1567	edible oils	1557:1567	Our results indicate that the EPS produced by Ensifer adhaerens JHT2 is a promising option for improving and maintaining stable emulsions in food prepared with edible oils.
29550419	4	26	dep	10	739:740	arg1	to					736:737	to	736:737	to	736:737	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	5	27	theme	0.5-1.0	907:913	arg1	%					914:914	%	914:914	%	914:914	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	2	28	theme	Ensifer	330:336	arg1	JHT2					348:351	Ensifer adhaerens JHT2	330:351	Ensifer adhaerens JHT2	330:351	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	29	theme	edible	392:397	arg1	oils					399:402	edible oils	392:402	edible oils (canola, corn, palm, olive and soy)	392:438	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	29	theme	edible	392:397	arg1	palm					419:422	palm	419:422	palm	419:422	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	29	theme	edible	392:397	arg1	olive					425:429	olive	425:429	olive	425:429	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	29	theme	edible	392:397	arg1	canola					405:410	canola	405:410	canola	405:410	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	29	theme	edible	392:397	arg1	corn					413:416	corn	413:416	corn	413:416	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	29	theme	edible	392:397	arg1	soy					435:437	soy	435:437	soy	435:437	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	0	30	theme	Chemical	0:7	arg1	characterization					9:24	Chemical characterization	0:24	Chemical characterization	0:24	Chemical characterization and potential application of exopolysaccharides produced by Ensifer adhaerens JHT2 as a bioemulsifier of edible oils.
29550419	7	31	theme	stable	1518:1523	arg1	emulsions					1525:1533	stable emulsions	1518:1533	stable emulsions	1518:1533	Our results indicate that the EPS produced by Ensifer adhaerens JHT2 is a promising option for improving and maintaining stable emulsions in food prepared with edible oils.
29550419	5	32	theme	-α-d-mannopyranosyl	1179:1197	arg1	units					1199:1203	(1→4)-α-d-mannopyranosyl units	1174:1203	(1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	1174:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	0	33	theme	potential	30:38	arg1	application					40:50	potential application	30:50	potential application	30:50	Chemical characterization and potential application of exopolysaccharides produced by Ensifer adhaerens JHT2 as a bioemulsifier of edible oils.
29550419	5	34	theme	soy	886:888	arg1	broth					890:894	trypticase soy broth	875:894	trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	875:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	0	35	theme	oils	138:141	arg1	JHT2					104:107	JHT2	104:107	JHT2	104:107	Chemical characterization and potential application of exopolysaccharides produced by Ensifer adhaerens JHT2 as a bioemulsifier of edible oils.
29550419	0	35	theme	oils	138:141	arg1	bioemulsifier					114:126	a bioemulsifier	112:126	a bioemulsifier of edible oils	112:141	Chemical characterization and potential application of exopolysaccharides produced by Ensifer adhaerens JHT2 as a bioemulsifier of edible oils.
29550419	6	36	theme	-β-d-glucopyranosyl	1286:1304	arg1	units					1272:1276	units	1272:1276	units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6	1272:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	0	37	theme	edible	131:136	arg1	oils					138:141	edible oils	131:141	edible oils	131:141	Chemical characterization and potential application of exopolysaccharides produced by Ensifer adhaerens JHT2 as a bioemulsifier of edible oils.
29550419	4	38	dep	pH	745:746	arg1	10					754:755	10	754:755	10	754:755	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	5	39	theme	highest	793:799	arg1	activity					816:823	The highest emulsification activity	789:823	The highest emulsification activity	789:823	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	40	theme	28-37°C.	948:955	arg1	Characterization					957:972	28-37°C. Characterization	948:972	28-37°C. Characterization of the bioemulsifier produced by JHT2	948:1010	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	6	41	theme	acetal	1361:1366	arg1	substitution					1368:1379	a pyruvic acid acetal substitution	1346:1379	a pyruvic acid acetal substitution at O-4 and O-6	1346:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	5	42	located	detected	829:836	arg2	activity					816:823	The highest emulsification activity	789:823	The highest emulsification activity	789:823	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	42	located	detected	829:836	arg1	supernatants					845:856	the supernatants	841:856	the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	841:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	4	43	theme	different	701:709	arg1	%					741:741	0.5 to 10%	732:741	0.5 to 10%	732:741	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	4	43	theme	different	701:709	arg1	concentrations					716:729	different NaCl concentrations	701:729	different NaCl concentrations (0.5 to 10%)	701:742	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	3	44	theme	JHT2	553:556	arg1	supernatant					566:576	JHT2 culture supernatant	553:576	JHT2 culture supernatant	553:576	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	1	45	theme	several	230:236	arg1	processing					275:284	food processing	270:284	food processing	270:284	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	1	45	theme	several	230:236	arg1	processes					249:257	several industrial processes	230:257	several industrial processes	230:257	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	5	46	theme	exopolysaccharides	1048:1065	arg1	characteristics					1029:1043	typical characteristics	1021:1043	typical characteristics of exopolysaccharides (EPS)	1021:1071	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	47	theme	%	914:914	arg1	temperatures					932:943	temperatures	932:943	temperatures	932:943	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	47	theme	%	914:914	arg1	pH6-7					922:926	pH6-7	922:926	pH6-7	922:926	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	47	theme	%	914:914	arg1	NaCl					916:919	0.5-1.0% NaCl	907:919	0.5-1.0% NaCl	907:919	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	6	48	theme	3-O-linked	1310:1319	arg1	galactopyranosyl					1321:1336	3-O-linked galactopyranosyl	1310:1336	3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6	1310:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	0	49	theme	exopolysaccharides	55:72	arg1	characterization					9:24	Chemical characterization	0:24	Chemical characterization	0:24	Chemical characterization and potential application of exopolysaccharides produced by Ensifer adhaerens JHT2 as a bioemulsifier of edible oils.
29550419	0	49	theme	exopolysaccharides	55:72	arg1	application					40:50	potential application	30:50	potential application	30:50	Chemical characterization and potential application of exopolysaccharides produced by Ensifer adhaerens JHT2 as a bioemulsifier of edible oils.
29550419	7	50	theme	promising	1471:1479	arg1	EPS					1427:1429	the EPS	1423:1429	the EPS produced by Ensifer adhaerens JHT2	1423:1464	Our results indicate that the EPS produced by Ensifer adhaerens JHT2 is a promising option for improving and maintaining stable emulsions in food prepared with edible oils.
29550419	7	50	theme	promising	1471:1479	arg1	option					1481:1486	a promising option	1469:1486	a promising option for improving and maintaining stable emulsions in food prepared with edible oils	1469:1567	Our results indicate that the EPS produced by Ensifer adhaerens JHT2 is a promising option for improving and maintaining stable emulsions in food prepared with edible oils.
29550419	6	51	dep	-β-d-glucopyranosyl	1286:1304	arg1	1→6					1282:1284	1→6	1282:1284	1→6	1282:1284	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	3	52	theme	canola	467:472	arg1	Emulsification					441:454	Emulsification	441:454	Emulsification of soy and canola oils	441:477	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	5	53	from	structure	1226:1234	arg1	branch					1210:1215	branch	1210:1215	branch from the structure at O-2	1210:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	1	54	from	important	217:225	arg1	processing					275:284	food processing	270:284	food processing	270:284	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	1	54	from	important	217:225	arg1	processes					249:257	several industrial processes	230:257	several industrial processes	230:257	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	5	55	theme	emulsification	801:814	arg1	activity					816:823	The highest emulsification activity	789:823	The highest emulsification activity	789:823	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	1	56	theme	industrial	238:247	arg1	processing					275:284	food processing	270:284	food processing	270:284	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	1	56	theme	industrial	238:247	arg1	processes					249:257	several industrial processes	230:257	several industrial processes	230:257	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	1	57	from	processes	249:257	arg1	important					217:225	important	217:225	important	217:225	Bioemulsifiers are able to stabilize oil-in-water emulsions and are very important in several industrial processes, including food processing.
29550419	3	58	theme	palm	613:616	arg1	oil					618:620	palm oil	613:620	palm oil (EI=100%)	613:630	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	3	58	theme	palm	613:616	arg1	%					629:629	EI=100%	623:629	EI=100%	623:629	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	4	59	theme	NaCl	711:714	arg1	%					741:741	0.5 to 10%	732:741	0.5 to 10%	732:741	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	4	59	theme	NaCl	711:714	arg1	concentrations					716:729	different NaCl concentrations	701:729	different NaCl concentrations (0.5 to 10%)	701:742	Bioemulsifier production was evaluated using nine culture media and different NaCl concentrations (0.5 to 10%), pH (4 to 10) and temperatures (28 to 42°C).
29550419	2	60	theme	adhaerens	338:346	arg1	JHT2					348:351	Ensifer adhaerens JHT2	330:351	Ensifer adhaerens JHT2	330:351	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	5	61	theme	1→4	1175:1177	arg1	units					1199:1203	(1→4)-α-d-mannopyranosyl units	1174:1203	(1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	1174:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	62	theme	-β-d-glucopyranosyl	1106:1124	arg1	backbone					1089:1096	a backbone	1087:1096	a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	1087:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	3	63	theme	oil	618:620	arg1	emulsification					595:608	the emulsification	591:608	the emulsification of palm oil (EI=100%)	591:630	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	3	64	theme	culture	558:564	arg1	supernatant					566:576	JHT2 culture supernatant	553:576	JHT2 culture supernatant	553:576	Emulsification of soy and canola oils was detected, but the highest emulsification index (EI) was obtained when JHT2 culture supernatant was used for the emulsification of palm oil (EI=100%).
29550419	5	65	contain	containing	896:905	arg2	NaCl					916:919	0.5-1.0% NaCl	907:919	0.5-1.0% NaCl	907:919	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	65	contain	containing	896:905	arg1	broth					890:894	trypticase soy broth	875:894	trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2	875:1241	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	65	contain	containing	896:905	arg2	temperatures					932:943	temperatures	932:943	temperatures	932:943	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	5	65	contain	containing	896:905	arg2	pH6-7					922:926	pH6-7	922:926	pH6-7	922:926	The highest emulsification activity was detected in the supernatants of JHT2 grown in trypticase soy broth containing 0.5-1.0% NaCl, pH6-7 and temperatures of 28-37°C. Characterization of the bioemulsifier produced by JHT2 revealed typical characteristics of exopolysaccharides (EPS), constituting a backbone of (1→4)-β-d-glucopyranosyl and (1→3)-β-D-galactopyranosyl alternating with (1→4)-α-d-mannopyranosyl units that branch from the structure at O-2.
29550419	7	66	theme	adhaerens	1451:1459	arg1	JHT2					1461:1464	Ensifer adhaerens JHT2	1443:1464	Ensifer adhaerens JHT2	1443:1464	Our results indicate that the EPS produced by Ensifer adhaerens JHT2 is a promising option for improving and maintaining stable emulsions in food prepared with edible oils.
29550419	2	67	dep	oils	399:402	arg1	oils					399:402	edible oils	392:402	edible oils (canola, corn, palm, olive and soy)	392:438	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	67	dep	oils	399:402	arg1	palm					419:422	palm	419:422	palm	419:422	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	67	dep	oils	399:402	arg1	olive					425:429	olive	425:429	olive	425:429	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	67	dep	oils	399:402	arg1	canola					405:410	canola	405:410	canola	405:410	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	67	dep	oils	399:402	arg1	corn					413:416	corn	413:416	corn	413:416	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	2	67	dep	oils	399:402	arg1	soy					435:437	soy	435:437	soy	435:437	In this study, a bioemulsifier produced by Ensifer adhaerens JHT2 was tested for its ability to emulsify edible oils (canola, corn, palm, olive and soy).
29550419	6	68	theme	galactopyranosyl	1321:1336	arg1	units					1272:1276	units	1272:1276	units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6	1272:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	6	69	theme	acid	1356:1359	arg1	substitution					1368:1379	a pyruvic acid acetal substitution	1346:1379	a pyruvic acid acetal substitution at O-4 and O-6	1346:1394	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
29550419	6	70	theme	Side	1244:1247	arg1	chains					1249:1254	Side chains	1244:1254	Side chains	1244:1254	Side chains are composed of units of (1→6)-β-d-glucopyranosyl and 3-O-linked galactopyranosyl bearing a pyruvic acid acetal substitution at O-4 and O-6.
30770376	4	0	theme	chromatography	942:955	arg1	column					957:962	a hydrophilic interaction chromatography column	916:962	a hydrophilic interaction chromatography column	916:962	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	0	1	theme	Spectrometry	217:228	arg1	Use					140:142	Use	140:142	Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	140:228	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	10	2	theme	transferrin	1842:1852	arg1	analysis					1854:1861	carbohydrate-deficient transferrin analysis	1819:1861	carbohydrate-deficient transferrin analysis	1819:1861	Additional CDGs can be diagnosed that would be missed by carbohydrate-deficient transferrin analysis.
30770376	6	3	theme	detection	1269:1277	arg1	range					1279:1283	the detection range	1265:1283	the detection range tested	1265:1290	The low end of the detection range tested was at 63 nmol/L for disialo-biantennary N-glycan.
30770376	7	4	from	majority	1347:1354	arg1	plasma					1379:1384	normal plasma	1372:1384	normal plasma	1372:1384	The majority of N-glycans in normal plasma had <1% abundance.
30770376	4	5	theme	hydrophilic	918:928	arg1	column					957:962	a hydrophilic interaction chromatography column	916:962	a hydrophilic interaction chromatography column	916:962	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	6	6	theme	low	1254:1256	arg1	end					1258:1260	The low end	1250:1260	The low end of the detection range tested	1250:1290	The low end of the detection range tested was at 63 nmol/L for disialo-biantennary N-glycan.
30770376	1	7	theme	Congenital	242:251	arg1	disorders					253:261	BACKGROUND Congenital disorders	231:261	BACKGROUND Congenital disorders of glycosylation (CDG)	231:284	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	5	8	dep	RESULTS	1087:1093	arg1	differed					1106:1113	differed	1106:1113	differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative	1106:1247	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	11	9	theme	therapeutic	1932:1942	arg1	significance					1944:1955	diagnostic and potentially therapeutic significance	1905:1955	diagnostic and potentially therapeutic significance	1905:1955	The assay provides novel biomarkers with diagnostic and potentially therapeutic significance.
30770376	7	10	contain	had	1386:1388	arg1	majority					1347:1354	The majority	1343:1354	The majority of N-glycans in normal plasma	1343:1384	The majority of N-glycans in normal plasma had <1% abundance.
30770376	7	10	contain	had	1386:1388	arg2	abundance					1394:1402	<1% abundance	1390:1402	<1% abundance	1390:1402	The majority of N-glycans in normal plasma had <1% abundance.
30770376	6	11	theme	disialo-biantennary	1313:1331	arg1	N-glycan					1333:1340	disialo-biantennary N-glycan	1313:1340	disialo-biantennary N-glycan	1313:1340	The low end of the detection range tested was at 63 nmol/L for disialo-biantennary N-glycan.
30770376	4	12	theme	plasma	794:799	arg1	glycoproteins					801:813	plasma glycoproteins	794:813	plasma glycoproteins	794:813	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	4	13	attach	linked	831:836	arg2	N-glycans					816:824	N-glycans	816:824	N-glycans	816:824	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	4	13	attach	linked	831:836	arg1	quinolone					843:851	a quinolone	841:851	a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column	841:962	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	0	14	theme	Injection-Electrospray	152:173	arg1	Spectrometry					217:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	5	15	theme	N-glycan	1126:1133	arg1	methods					1145:1151	other N-glycan profiling methods	1120:1151	other N-glycan profiling methods	1120:1151	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	8	16	with	patients	1440:1447	arg1	diagnoses					1460:1468	known diagnoses	1454:1468	known diagnoses of 11 different CDG subtypes	1454:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	0	17	theme	Time-of-Flight	197:210	arg1	Spectrometry					217:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	4	18	theme	PNGase	772:777	arg1	digestion					781:789	PNGase F digestion	772:789	PNGase F digestion of plasma glycoproteins	772:813	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	0	19	theme	N-Glycan	65:72	arg1	Profiling					74:82	Plasma Protein N-Glycan Profiling	50:82	Plasma Protein N-Glycan Profiling	50:82	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	5	20	theme	free	1211:1214	arg1	glycans					1216:1222	circulating free glycans	1199:1222	circulating free glycans	1199:1222	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	3	21	theme	N-glycan	653:660	arg1	assay					662:666	a plasma N-glycan assay	644:666	a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	644:755	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	2	22	attach	linked	527:532	arg3	disorders					415:423	disorders	415:423	disorders	415:423	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	2	22	attach	linked	527:532	arg2	residues					474:481	carbohydrate residues	461:481	carbohydrate residues	461:481	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	2	22	attach	linked	527:532	arg1	molecules					548:556	asparagine molecules	537:556	asparagine molecules in peptides	537:568	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	2	22	attach	linked	527:532	arg3	majority					386:393	The majority	382:393	The majority of CDG subtypes	382:409	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	2	22	attach	linked	527:532	arg2	N-glycans					492:500	N-glycans	492:500	N-glycans	492:500	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	11	23	theme	novel	1883:1887	arg1	biomarkers					1889:1898	novel biomarkers	1883:1898	novel biomarkers	1883:1898	The assay provides novel biomarkers with diagnostic and potentially therapeutic significance.
30770376	8	24	theme	normal	1566:1571	arg1	glycosylation					1590:1602	normal N-linked protein glycosylation	1566:1602	normal N-linked protein glycosylation	1566:1602	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	8	25	theme	N-glycan	1414:1421	arg1	profiles					1423:1430	Abnormal N-glycan profiles	1405:1430	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes	1405:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	8	26	theme	protein	1582:1588	arg1	glycosylation					1590:1602	normal N-linked protein glycosylation	1566:1602	normal N-linked protein glycosylation	1566:1602	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	0	27	theme	Congenital	99:108	arg1	Disorders					110:118	Diagnosing Congenital Disorders	88:118	Diagnosing Congenital Disorders of Glycosylation	88:135	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	9	28	dep	CONCLUSIONS	1652:1662	arg1	improved					1735:1742	improved	1735:1742	was much improved with this method	1726:1759	CONCLUSIONS The clinical specificity and sensitivity of N-glycan analysis was much improved with this method.
30770376	4	29	theme	isotope-labeled	1032:1046	arg1	standard					1077:1084	standard	1077:1084	standard	1077:1084	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	4	29	theme	isotope-labeled	1032:1046	arg1	glycopeptide					1048:1059	a stable isotope-labeled glycopeptide	1023:1059	a stable isotope-labeled glycopeptide	1023:1059	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	2	30	theme	glycosylation	437:449	arg1	disorders					415:423	disorders	415:423	disorders	415:423	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	2	30	theme	glycosylation	437:449	arg1	majority					386:393	The majority	382:393	The majority of CDG subtypes	382:409	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	9	31	theme	clinical	1668:1675	arg1	specificity					1677:1687	clinical specificity	1668:1687	clinical specificity	1668:1687	CONCLUSIONS The clinical specificity and sensitivity of N-glycan analysis was much improved with this method.
30770376	8	32	theme	transferrin	1630:1640	arg1	analysis					1642:1649	carbohydrate-deficient transferrin analysis	1607:1649	carbohydrate-deficient transferrin analysis	1607:1649	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	8	33	theme	known	1454:1458	arg1	diagnoses					1460:1468	known diagnoses	1454:1468	known diagnoses of 11 different CDG subtypes	1454:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	10	34	theme	Additional	1762:1771	arg1	CDGs					1773:1776	Additional CDGs	1762:1776	Additional CDGs	1762:1776	Additional CDGs can be diagnosed that would be missed by carbohydrate-deficient transferrin analysis.
30770376	8	35	theme	different	1476:1484	arg1	subtypes					1490:1497	11 different CDG subtypes	1473:1497	11 different CDG subtypes	1473:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	2	36	theme	carbohydrate	461:472	arg1	residues					474:481	carbohydrate residues	461:481	carbohydrate residues	461:481	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	2	36	theme	carbohydrate	461:472	arg1	N-glycans					492:500	N-glycans	492:500	N-glycans	492:500	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	1	37	theme	disorders	333:341	arg1	disorders					333:341	metabolic disorders	323:341	metabolic disorders	323:341	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	1	37	theme	disorders	333:341	arg1	groups					313:318	1 of the largest groups	296:318	1 of the largest groups of metabolic disorders with >130 subtypes identified to date	296:379	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	7	38	theme	%	1392:1392	arg1	abundance					1394:1402	<1% abundance	1390:1402	<1% abundance	1390:1402	The majority of N-glycans in normal plasma had <1% abundance.
30770376	3	39	theme	time-of-flight	724:737	arg1	spectrometry					744:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	4	40	theme	reducing	890:897	arg1	end					899:901	the reducing end	886:901	the reducing end	886:901	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	9	41	theme	analysis	1717:1724	arg1	sensitivity					1693:1703	sensitivity	1693:1703	sensitivity	1693:1703	CONCLUSIONS The clinical specificity and sensitivity of N-glycan analysis was much improved with this method.
30770376	9	41	theme	analysis	1717:1724	arg1	specificity					1677:1687	clinical specificity	1668:1687	clinical specificity	1668:1687	CONCLUSIONS The clinical specificity and sensitivity of N-glycan analysis was much improved with this method.
30770376	3	42	theme	injection-electrospray	679:700	arg1	spectrometry					744:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	8	43	theme	subtypes	1490:1497	arg1	diagnoses					1460:1468	known diagnoses	1454:1468	known diagnoses of 11 different CDG subtypes	1454:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	10	44	theme	carbohydrate-deficient	1819:1840	arg1	analysis					1854:1861	carbohydrate-deficient transferrin analysis	1819:1861	carbohydrate-deficient transferrin analysis	1819:1861	Additional CDGs can be diagnosed that would be missed by carbohydrate-deficient transferrin analysis.
30770376	5	45	from	glycans	1216:1222	arg1	contamination					1180:1192	any contamination	1176:1192	any contamination from circulating free glycans	1176:1222	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	5	46	theme	other	1120:1124	arg1	methods					1145:1151	other N-glycan profiling methods	1120:1151	other N-glycan profiling methods	1120:1151	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	7	47	theme	normal	1372:1377	arg1	plasma					1379:1384	normal plasma	1372:1384	normal plasma	1372:1384	The majority of N-glycans in normal plasma had <1% abundance.
30770376	4	48	theme	amine	871:875	arg1	group					877:881	a transient amine group	859:881	a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column	859:962	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	7	49	theme	N-glycans	1359:1367	arg1	majority					1347:1354	The majority	1343:1354	The majority of N-glycans in normal plasma	1343:1384	The majority of N-glycans in normal plasma had <1% abundance.
30770376	2	50	theme	CDG	398:400	arg1	subtypes					402:409	CDG subtypes	398:409	CDG subtypes	398:409	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	1	51	theme	of	298:299	arg1	disorders					333:341	metabolic disorders	323:341	metabolic disorders	323:341	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	1	51	theme	of	298:299	arg1	groups					313:318	1 of the largest groups	296:318	1 of the largest groups of metabolic disorders with >130 subtypes identified to date	296:379	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	4	52	theme	interaction	930:940	arg1	column					957:962	a hydrophilic interaction chromatography column	916:962	a hydrophilic interaction chromatography column	916:962	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	2	53	link	N-linked	428:435	arg1	glycosylation					437:449	N-linked glycosylation	428:449	N-linked glycosylation	428:449	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	3	54	theme	diagnostic	586:595	arg1	capability					597:606	the diagnostic capability	582:606	the diagnostic capability for CDG	582:614	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	1	55	theme	largest	305:311	arg1	disorders					333:341	metabolic disorders	323:341	metabolic disorders	323:341	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	1	55	theme	largest	305:311	arg1	groups					313:318	1 of the largest groups	296:318	1 of the largest groups of metabolic disorders with >130 subtypes identified to date	296:379	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	9	56	dep	specificity	1677:1687	arg1	The					1664:1666	The	1664:1666	The	1664:1666	CONCLUSIONS The clinical specificity and sensitivity of N-glycan analysis was much improved with this method.
30770376	0	57	theme	Plasma	50:55	arg1	Profiling					74:82	Plasma Protein N-Glycan Profiling	50:82	Plasma Protein N-Glycan Profiling	50:82	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	1	58	theme	BACKGROUND	231:240	arg1	disorders					253:261	BACKGROUND Congenital disorders	231:261	BACKGROUND Congenital disorders of glycosylation (CDG)	231:284	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	4	59	theme	accurate	988:995	arg1	mass					997:1000	accurate mass	988:1000	accurate mass	988:1000	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	8	60	theme	Abnormal	1405:1412	arg1	profiles					1423:1430	Abnormal N-glycan profiles	1405:1430	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes	1405:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	4	61	gly	glycoproteins	801:813	arg1	glycoproteins					801:813	plasma glycoproteins	794:813	plasma glycoproteins	794:813	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	1	62	theme	glycosylation	266:278	arg1	disorders					253:261	BACKGROUND Congenital disorders	231:261	BACKGROUND Congenital disorders of glycosylation (CDG)	231:284	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	2	63	from	molecules	548:556	arg1	peptides					561:568	peptides	561:568	peptides	561:568	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	0	64	theme	Ionization-Quadrupole	175:195	arg1	Spectrometry					217:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	4	65	from	end	899:901	arg1	group					877:881	a transient amine group	859:881	a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column	859:962	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	0	66	theme	Mass	212:215	arg1	Spectrometry					217:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	5	67	theme	profiling	1135:1143	arg1	methods					1145:1151	other N-glycan profiling methods	1120:1151	other N-glycan profiling methods	1120:1151	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	4	68	theme	glycoproteins	801:813	arg1	digestion					781:789	PNGase F digestion	772:789	PNGase F digestion of plasma glycoproteins	772:813	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	0	69	theme	Profiling	74:82	arg1	Sensitivity					19:29	Clinical Sensitivity	10:29	Clinical Sensitivity	10:29	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	0	69	theme	Profiling	74:82	arg1	Specificity					35:45	Specificity	35:45	Specificity	35:45	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	3	70	theme	plasma	646:651	arg1	assay					662:666	a plasma N-glycan assay	644:666	a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	644:755	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	2	71	theme	asparagine	537:546	arg1	molecules					548:556	asparagine molecules	537:556	asparagine molecules in peptides	537:568	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	8	72	theme	N-linked	1573:1580	arg1	glycosylation					1590:1602	normal N-linked protein glycosylation	1566:1602	normal N-linked protein glycosylation	1566:1602	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	6	73	theme	range	1279:1283	arg1	end					1258:1260	The low end	1250:1260	The low end of the detection range tested	1250:1290	The low end of the detection range tested was at 63 nmol/L for disialo-biantennary N-glycan.
30770376	0	74	theme	Diagnosing	88:97	arg1	Disorders					110:118	Diagnosing Congenital Disorders	88:118	Diagnosing Congenital Disorders of Glycosylation	88:135	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	4	75	theme	F	779:779	arg1	digestion					781:789	PNGase F digestion	772:789	PNGase F digestion of plasma glycoproteins	772:813	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	4	76	gly	glycopeptide	1048:1059	arg2	standard					1077:1084	standard	1077:1084	standard	1077:1084	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	4	76	gly	glycopeptide	1048:1059	arg2	glycopeptide					1048:1059	a stable isotope-labeled glycopeptide	1023:1059	a stable isotope-labeled glycopeptide	1023:1059	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	8	77	theme	carbohydrate-deficient	1607:1628	arg1	transferrin					1630:1640	carbohydrate-deficient transferrin	1607:1640	carbohydrate-deficient transferrin analysis	1607:1649	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	11	78	theme	diagnostic	1905:1914	arg1	significance					1944:1955	diagnostic and potentially therapeutic significance	1905:1955	diagnostic and potentially therapeutic significance	1905:1955	The assay provides novel biomarkers with diagnostic and potentially therapeutic significance.
30770376	0	79	theme	Glycosylation	123:135	arg1	Disorders					110:118	Diagnosing Congenital Disorders	88:118	Diagnosing Congenital Disorders of Glycosylation	88:135	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	5	80	theme	contamination	1180:1192	arg1	free					1168:1171	free	1168:1171	free	1168:1171	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	4	81	theme	stable	1025:1030	arg1	standard					1077:1084	standard	1077:1084	standard	1077:1084	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	4	81	theme	stable	1025:1030	arg1	glycopeptide					1048:1059	a stable isotope-labeled glycopeptide	1023:1059	a stable isotope-labeled glycopeptide	1023:1059	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	2	82	theme	N-linked	428:435	arg1	glycosylation					437:449	N-linked glycosylation	428:449	N-linked glycosylation	428:449	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	0	83	theme	Clinical	10:17	arg1	Sensitivity					19:29	Clinical Sensitivity	10:29	Clinical Sensitivity	10:29	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	5	84	theme	circulating	1199:1209	arg1	glycans					1216:1222	circulating free glycans	1199:1222	circulating free glycans	1199:1222	RESULTS This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative.
30770376	0	85	theme	Flow	147:150	arg1	Spectrometry					217:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry	147:228	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	1	86	theme	metabolic	323:331	arg1	disorders					333:341	metabolic disorders	323:341	metabolic disorders	323:341	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	7	87	theme	<1	1390:1391	arg1	%					1392:1392	%	1392:1392	%	1392:1392	The majority of N-glycans in normal plasma had <1% abundance.
30770376	3	88	theme	ionization-quadrupole	702:722	arg1	spectrometry					744:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	9	89	theme	N-glycan	1708:1715	arg1	analysis					1717:1724	N-glycan analysis	1708:1724	N-glycan analysis	1708:1724	CONCLUSIONS The clinical specificity and sensitivity of N-glycan analysis was much improved with this method.
30770376	3	90	theme	flow	674:677	arg1	spectrometry					744:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	0	91	theme	Protein	57:63	arg1	Profiling					74:82	Plasma Protein N-Glycan Profiling	50:82	Plasma Protein N-Glycan Profiling	50:82	Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection-Electrospray Ionization-Quadrupole Time-of-Flight Mass Spectrometry.
30770376	1	92	with	groups	313:318	arg1	subtypes					353:360	>130 subtypes	348:360	>130 subtypes identified to date	348:379	BACKGROUND Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with >130 subtypes identified to date.
30770376	8	93	theme	CDG	1486:1488	arg1	subtypes					1490:1497	11 different CDG subtypes	1473:1497	11 different CDG subtypes	1473:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	8	94	from	patients	1440:1447	arg1	profiles					1423:1430	Abnormal N-glycan profiles	1405:1430	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes	1405:1497	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	4	95	dep	METHODS	758:764	arg1	identified					974:983	identified	974:983	identified by accurate mass	974:1000	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	4	95	dep	METHODS	758:764	arg1	linked					831:836	linked	831:836	linked	831:836	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	8	96	link	N-linked	1573:1580	arg1	glycosylation					1590:1602	normal N-linked protein glycosylation	1566:1602	normal N-linked protein glycosylation	1566:1602	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	8	97	contain	have	1561:1564	arg2	glycosylation					1590:1602	normal N-linked protein glycosylation	1566:1602	normal N-linked protein glycosylation	1566:1602	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	8	97	contain	have	1561:1564	arg1	which					1523:1527	which	1523:1527	which	1523:1527	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	8	97	contain	have	1561:1564	arg1	some					1515:1518	some	1515:1518	some	1515:1518	Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.
30770376	3	98	theme	mass	739:742	arg1	spectrometry					744:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry	674:755	To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.
30770376	4	99	theme	transient	861:869	arg1	group					877:881	a transient amine group	859:881	a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column	859:962	METHODS After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.
30770376	2	100	theme	subtypes	402:409	arg1	disorders					415:423	disorders	415:423	disorders	415:423	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
30770376	2	100	theme	subtypes	402:409	arg1	majority					386:393	The majority	382:393	The majority of CDG subtypes	382:409	The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides.
31306420	4	0	theme	American	939:946	arg1	AMCR					955:958	AMCR	955:958	AMCR	955:958	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	0	theme	American	939:946	arg1	crows					948:952	American crows	939:952	American crows (AMCR)	939:959	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	1	1	theme	West	219:222	arg1	WNV					236:238	WNV	236:238	WNV	236:238	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	1	1	theme	West	219:222	arg1	virus					229:233	West Nile virus	219:233	West Nile virus (WNV)	219:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	12	2	theme	differential	1829:1840	arg1	host					1848:1851	differential avian host and vector competence phenotypes	1829:1884	host	1848:1851	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	2	3	with	isolates	352:359	arg1	patterns					398:405	altered E protein glycosylation patterns	366:405	altered E protein glycosylation patterns	366:405	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	8	4	theme	Only	1473:1476	arg1	NYP					1478:1480	Only NYP	1473:1480	Only NYP	1473:1480	Only NYP showed reduced vector competence in both Cx.
31306420	5	5	theme	lower	1086:1090	arg1	sensitivity					1111:1121	lower pH and temperature sensitivity	1086:1121	lower pH and temperature sensitivity	1086:1121	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	0	6	link	N-linked	0:7	arg1	glycosylation					9:21	N-linked glycosylation	0:21	N-linked glycosylation of the West Nile virus envelope protein	0:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	4	7	theme	Culex	988:992	arg1	quinquefasciatus					994:1009	Culex quinquefasciatus	988:1009	Culex quinquefasciatus	988:1009	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	1	8	theme	amino	160:164	arg1	position					171:178	amino acid position 154-156	160:186	amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	160:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	2	9	located	observed	417:424	arg1	isolates					433:440	WNV isolates	429:440	WNV isolates	429:440	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	2	9	located	observed	417:424	arg2	isolates					352:359	Naturally occurring isolates	332:359	Naturally occurring isolates with altered E protein glycosylation patterns	332:405	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	1	10	attach	linked	244:249	arg2	motif					151:155	The N-linked glycosylation motif	124:155	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	124:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	1	10	attach	linked	244:249	arg1	neuroinvasiveness					270:286	enhanced murine neuroinvasiveness	254:286	enhanced murine neuroinvasiveness	254:286	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	1	10	attach	linked	244:249	arg1	pathogenicity					295:307	avian pathogenicity	289:307	avian pathogenicity	289:307	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	1	10	attach	linked	244:249	arg1	competence					320:329	vector competence	313:329	vector competence	313:329	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	4	11	theme	glycosylation	807:819	arg1	viruses					828:834	These WNV glycosylation mutant viruses	797:834	These WNV glycosylation mutant viruses	797:834	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	11	12	theme	oral	1664:1667	arg1	infectivity					1669:1679	higher mosquito oral infectivity	1648:1679	higher mosquito oral infectivity	1648:1679	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	7	13	dep	NYP	1418:1420	arg1	viruses					1430:1436	viruses	1430:1436	viruses	1430:1436	In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes.
31306420	1	14	theme	envelope	195:202	arg1	protein					208:214	the envelope (E) protein	191:214	the envelope (E) protein of West Nile virus (WNV)	191:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	12	15	theme	amino	1784:1788	arg1	polymorphisms					1795:1807	amino acid polymorphisms	1784:1807	amino acid polymorphisms at E154/156	1784:1819	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	11	16	theme	higher	1648:1653	arg1	infectivity					1669:1679	higher mosquito oral infectivity	1648:1679	higher mosquito oral infectivity	1648:1679	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	6	17	from	effects	1235:1241	arg1	competence					1265:1274	avian and mosquito competence	1246:1274	avian and mosquito competence	1246:1274	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	2	18	theme	vector	527:532	arg1	competence					534:543	vector competence	527:543	vector competence	527:543	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	2	19	from	effects	465:471	arg1	pathogenesis					510:521	avian host pathogenesis	499:521	avian host pathogenesis	499:521	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	2	19	from	effects	465:471	arg1	competence					534:543	vector competence	527:543	vector competence	527:543	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	11	20	theme	KYS	1742:1744	arg1	NYS					1699:1701	glycosylated NYS	1686:1701	glycosylated NYS	1686:1701	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	20	theme	KYS	1742:1744	arg1	mutants					1746:1752	KYS mutants	1742:1752	KYS mutants	1742:1752	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	21	theme	similar	1589:1595	arg1	properties					1613:1622	similar avian virulence properties	1589:1622	similar avian virulence properties	1589:1622	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	21	theme	similar	1589:1595	arg1	NYS					1627:1629	NYS	1627:1629	NYS	1627:1629	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	1	22	gly	glycosylation	137:149	arg2	motif					151:155	The N-linked glycosylation motif	124:155	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	124:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	3	23	theme	present	587:593	arg1	study					595:599	the present study	583:599	the present study	583:599	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	4	24	theme	in	859:860	arg1	growth					868:873	growth	868:873	growth	868:873	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	0	25	theme	protein	55:61	arg1	glycosylation					9:21	N-linked glycosylation	0:21	N-linked glycosylation of the West Nile virus envelope protein	0:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	1	26	theme	N-linked	128:135	arg1	motif					151:155	The N-linked glycosylation motif	124:155	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	124:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	12	27	theme	glycosylation	1911:1923	arg1	status					1925:1930	E-protein glycosylation status	1901:1930	E-protein glycosylation status	1901:1930	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	3	28	theme	parental	710:717	arg1	clone					745:749	a parental WNV (NYS) cDNA infectious clone	708:749	a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses	708:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	6	29	theme	in	1195:1196	arg1	results					1203:1209	in vivo results	1195:1209	in vivo results	1195:1209	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	1	30	theme	avian	289:293	arg1	pathogenicity					295:307	avian pathogenicity	289:307	avian pathogenicity	289:307	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	3	31	theme	infectious	734:743	arg1	clone					745:749	a parental WNV (NYS) cDNA infectious clone	708:749	a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses	708:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	2	32	theme	polymorphisms	482:494	arg1	effects					465:471	the specific effects	452:471	the specific effects of these polymorphisms on avian host pathogenesis and vector competence	452:543	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	11	33	theme	virulence	1603:1611	arg1	properties					1613:1622	similar avian virulence properties	1589:1622	similar avian virulence properties	1589:1622	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	33	theme	virulence	1603:1611	arg1	NYS					1627:1629	NYS	1627:1629	NYS	1627:1629	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	3	34	theme	mutant	781:786	arg1	viruses					788:794	WNV glycosylation mutant viruses	763:794	WNV glycosylation mutant viruses	763:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	5	35	theme	DEL	1158:1160	arg1	viruses					1162:1168	A'DEL viruses	1156:1168	A'DEL viruses	1156:1168	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	1	36	theme	virus	229:233	arg1	protein					208:214	the envelope (E) protein	191:214	the envelope (E) protein of West Nile virus (WNV)	191:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	6	37	dep	in	1195:1196	arg1	vivo					1198:1201	vivo	1198:1201	vivo	1198:1201	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	3	38	theme	WNV	763:765	arg1	viruses					788:794	WNV glycosylation mutant viruses	763:794	WNV glycosylation mutant viruses	763:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	4	39	theme	host	920:923	arg1	competence					925:934	host competence	920:934	host competence	920:934	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	2	40	theme	specific	456:463	arg1	effects					465:471	the specific effects	452:471	the specific effects of these polymorphisms on avian host pathogenesis and vector competence	452:543	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	2	41	theme	occurring	342:350	arg1	isolates					352:359	Naturally occurring isolates	332:359	Naturally occurring isolates with altered E protein glycosylation patterns	332:405	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	0	42	theme	N-linked	0:7	arg1	glycosylation					9:21	N-linked glycosylation	0:21	N-linked glycosylation of the West Nile virus envelope protein	0:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	2	43	theme	glycosylation	384:396	arg1	patterns					398:405	altered E protein glycosylation patterns	366:405	altered E protein glycosylation patterns	366:405	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	5	44	theme	higher	1056:1061	arg1	replication					1069:1079	higher viral replication	1056:1079	higher viral replication	1056:1079	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	12	45	from	E154/156	1812:1819	arg1	polymorphisms					1795:1807	amino acid polymorphisms	1784:1807	amino acid polymorphisms at E154/156	1784:1819	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	3	46	theme	acid	608:611	arg1	SYS					648:650	SYS	648:650	SYS	648:650	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	46	theme	acid	608:611	arg1	NYP					633:635	NYP	633:635	NYP	633:635	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	46	theme	acid	608:611	arg1	NYF					638:640	NYF	638:640	NYF	638:640	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	46	theme	acid	608:611	arg1	KYS					653:655	KYS	653:655	KYS	653:655	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	46	theme	acid	608:611	arg1	polymorphisms					613:625	amino acid polymorphisms	602:625	amino acid polymorphisms	602:625	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	46	theme	acid	608:611	arg1	deletion					661:668	deletion	661:668	deletion (A'DEL)	661:676	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	46	theme	acid	608:611	arg1	SYP					643:645	SYP	643:645	SYP	643:645	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	2	47	theme	E	374:374	arg1	patterns					398:405	altered E protein glycosylation patterns	366:405	altered E protein glycosylation patterns	366:405	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	0	48	theme	West	30:33	arg1	virus					40:44	West Nile virus	30:44	the West Nile virus envelope protein	26:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	4	49	from	temperature-sensitivity	892:914	arg1	quinquefasciatus					994:1009	Culex quinquefasciatus	988:1009	Culex quinquefasciatus	988:1009	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	49	from	temperature-sensitivity	892:914	arg1	AMCR					955:958	AMCR	955:958	AMCR	955:958	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	49	from	temperature-sensitivity	892:914	arg1	HOSP					978:981	HOSP	978:981	HOSP	978:981	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	49	from	temperature-sensitivity	892:914	arg1	crows					948:952	American crows	939:952	American crows (AMCR)	939:959	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	49	from	temperature-sensitivity	892:914	arg1	sparrows					968:975	house sparrows	962:975	house sparrows (HOSP)	962:982	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	0	50	gly	glycosylation	9:21	arg1	protein					55:61	the West Nile virus envelope protein	26:61	the West Nile virus envelope protein	26:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	12	51	theme	avian	1842:1846	arg1	host					1848:1851	differential avian host and vector competence phenotypes	1829:1884	host	1848:1851	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	2	52	theme	WNV	429:431	arg1	isolates					433:440	WNV isolates	429:440	WNV isolates	429:440	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	0	53	theme	virus	40:44	arg1	protein					55:61	the West Nile virus envelope protein	26:61	the West Nile virus envelope protein	26:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	4	54	from	pH-sensitivity	876:889	arg1	quinquefasciatus					994:1009	Culex quinquefasciatus	988:1009	Culex quinquefasciatus	988:1009	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	54	from	pH-sensitivity	876:889	arg1	AMCR					955:958	AMCR	955:958	AMCR	955:958	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	54	from	pH-sensitivity	876:889	arg1	HOSP					978:981	HOSP	978:981	HOSP	978:981	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	54	from	pH-sensitivity	876:889	arg1	crows					948:952	American crows	939:952	American crows (AMCR)	939:959	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	54	from	pH-sensitivity	876:889	arg1	sparrows					968:975	house sparrows	962:975	house sparrows (HOSP)	962:982	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	3	55	from	reverse	684:690	arg1	study					595:599	the present study	583:599	the present study	583:599	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	11	56	theme	Glycosylated	1562:1573	arg1	NYT					1575:1577	Glycosylated NYT	1562:1577	Glycosylated NYT	1562:1577	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	6	57	theme	status	1329:1334	arg1	independent					1286:1296	independent	1286:1296	independent	1286:1296	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	5	58	theme	pH	1092:1093	arg1	sensitivity					1111:1121	lower pH and temperature sensitivity	1086:1121	lower pH and temperature sensitivity	1086:1121	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	12	59	theme	independent	1886:1896	arg1	host					1848:1851	differential avian host and vector competence phenotypes	1829:1884	host	1848:1851	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	2	60	theme	altered	366:372	arg1	patterns					398:405	altered E protein glycosylation patterns	366:405	altered E protein glycosylation patterns	366:405	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	6	61	theme	E-protein	1305:1313	arg1	status					1329:1334	the E-protein glycosylation status	1301:1334	the E-protein glycosylation status	1301:1334	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	5	62	theme	temperature	1099:1109	arg1	sensitivity					1111:1121	lower pH and temperature sensitivity	1086:1121	lower pH and temperature sensitivity	1086:1121	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	12	63	theme	competence	1864:1873	arg1	phenotypes					1875:1884	differential avian host and vector competence phenotypes	1829:1884	phenotypes	1875:1884	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	3	64	from	study	595:599	arg1	reverse					684:690	reverse	684:690	reverse	684:690	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	1	65	theme	Nile	224:227	arg1	WNV					236:238	WNV	236:238	WNV	236:238	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	1	65	theme	Nile	224:227	arg1	virus					229:233	West Nile virus	219:233	West Nile virus (WNV)	219:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	6	66	theme	asymmetric	1224:1233	arg1	effects					1235:1241	asymmetric effects	1224:1241	asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status	1224:1334	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	1	67	theme	enhanced	254:261	arg1	neuroinvasiveness					270:286	enhanced murine neuroinvasiveness	254:286	enhanced murine neuroinvasiveness	254:286	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	1	68	theme	acid	166:169	arg1	position					171:178	amino acid position 154-156	160:186	amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	160:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	12	69	theme	acid	1790:1793	arg1	polymorphisms					1795:1807	amino acid polymorphisms	1784:1807	amino acid polymorphisms at E154/156	1784:1819	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	0	70	theme	vector	105:110	arg1	competence					112:121	vector competence	105:121	vector competence	105:121	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	7	71	theme	attenuated	1450:1459	arg1	phenotypes					1461:1470	attenuated phenotypes	1450:1470	attenuated phenotypes	1450:1470	In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes.
31306420	2	72	theme	host	505:508	arg1	pathogenesis					510:521	avian host pathogenesis	499:521	avian host pathogenesis	499:521	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	4	73	theme	WNV	803:805	arg1	viruses					828:834	These WNV glycosylation mutant viruses	797:834	These WNV glycosylation mutant viruses	797:834	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	1	74	theme	murine	263:268	arg1	neuroinvasiveness					270:286	enhanced murine neuroinvasiveness	254:286	enhanced murine neuroinvasiveness	254:286	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	7	75	with	viremias	1387:1394	arg1	exception					1405:1413	the exception	1401:1413	the exception of NYP and KYS viruses	1401:1436	In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes.
31306420	7	76	theme	KYS	1426:1428	arg1	exception					1405:1413	the exception	1401:1413	the exception of NYP and KYS viruses	1401:1436	In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes.
31306420	12	77	theme	status	1925:1930	arg1	independent					1886:1896	independent	1886:1896	independent	1886:1896	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	11	78	theme	mosquito	1655:1662	arg1	infectivity					1669:1679	higher mosquito oral infectivity	1648:1679	higher mosquito oral infectivity	1648:1679	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	4	79	dep	in	859:860	arg1	vitro					862:866	vitro	862:866	vitro	862:866	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	0	80	theme	Nile	35:38	arg1	virus					40:44	West Nile virus	30:44	the West Nile virus envelope protein	26:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	3	81	theme	cDNA	729:732	arg1	clone					745:749	a parental WNV (NYS) cDNA infectious clone	708:749	a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses	708:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	7	82	theme	NYP	1418:1420	arg1	exception					1405:1413	the exception	1401:1413	the exception of NYP and KYS viruses	1401:1436	In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes.
31306420	11	83	gly	glycosylated	1686:1697	arg1	NYS					1699:1701	glycosylated NYS	1686:1701	glycosylated NYS	1686:1701	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	83	gly	glycosylated	1686:1697	arg1	SYP					1734:1736	SYP	1734:1736	SYP	1734:1736	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	83	gly	glycosylated	1686:1697	arg1	NYF					1729:1731	NYF	1729:1731	NYF	1729:1731	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	83	gly	glycosylated	1686:1697	arg1	NYP					1724:1726	NYP	1724:1726	NYP	1724:1726	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	83	gly	glycosylated	1686:1697	arg1	mutants					1746:1752	KYS mutants	1742:1752	KYS mutants	1742:1752	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	84	theme	avian	1597:1601	arg1	properties					1613:1622	similar avian virulence properties	1589:1622	similar avian virulence properties	1589:1622	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	84	theme	avian	1597:1601	arg1	NYS					1627:1629	NYS	1627:1629	NYS	1627:1629	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	1	85	from	position	171:178	arg1	motif					151:155	The N-linked glycosylation motif	124:155	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	124:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	3	86	theme	NYS	724:726	arg1	clone					745:749	a parental WNV (NYS) cDNA infectious clone	708:749	a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses	708:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	5	87	gly	glycosylated	1028:1039	arg1	viruses					1041:1047	NYT glycosylated viruses	1024:1047	NYT glycosylated viruses	1024:1047	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	4	88	from	growth	868:873	arg1	quinquefasciatus					994:1009	Culex quinquefasciatus	988:1009	Culex quinquefasciatus	988:1009	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	88	from	growth	868:873	arg1	AMCR					955:958	AMCR	955:958	AMCR	955:958	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	88	from	growth	868:873	arg1	HOSP					978:981	HOSP	978:981	HOSP	978:981	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	88	from	growth	868:873	arg1	crows					948:952	American crows	939:952	American crows (AMCR)	939:959	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	88	from	growth	868:873	arg1	sparrows					968:975	house sparrows	962:975	house sparrows (HOSP)	962:982	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	1	89	theme	glycosylation	137:149	arg1	motif					151:155	The N-linked glycosylation motif	124:155	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	124:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	12	90	theme	E-protein	1901:1909	arg1	status					1925:1930	E-protein glycosylation status	1901:1930	E-protein glycosylation status	1901:1930	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	3	91	theme	WNV	719:721	arg1	clone					745:749	a parental WNV (NYS) cDNA infectious clone	708:749	a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses	708:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	7	92	theme	comparable	1376:1385	arg1	viremias					1387:1394	comparable viremias	1376:1394	comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes	1376:1470	In AMCRs and HOSPs, all viruses showed comparable viremias with the exception of NYP and KYS viruses that showed attenuated phenotypes.
31306420	4	93	theme	mutant	821:826	arg1	viruses					828:834	These WNV glycosylation mutant viruses	797:834	These WNV glycosylation mutant viruses	797:834	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	1	94	theme	vector	313:318	arg1	competence					320:329	vector competence	313:329	vector competence	313:329	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	8	95	theme	vector	1497:1502	arg1	competence					1504:1513	reduced vector competence	1489:1513	reduced vector competence	1489:1513	Only NYP showed reduced vector competence in both Cx.
31306420	3	96	theme	glycosylation	767:779	arg1	viruses					788:794	WNV glycosylation mutant viruses	763:794	WNV glycosylation mutant viruses	763:794	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	2	97	theme	avian	499:503	arg1	pathogenesis					510:521	avian host pathogenesis	499:521	avian host pathogenesis	499:521	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	6	98	theme	mosquito	1256:1263	arg1	competence					1265:1274	avian and mosquito competence	1246:1274	avian and mosquito competence	1246:1274	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	4	99	from	competence	925:934	arg1	quinquefasciatus					994:1009	Culex quinquefasciatus	988:1009	Culex quinquefasciatus	988:1009	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	99	from	competence	925:934	arg1	AMCR					955:958	AMCR	955:958	AMCR	955:958	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	99	from	competence	925:934	arg1	HOSP					978:981	HOSP	978:981	HOSP	978:981	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	99	from	competence	925:934	arg1	crows					948:952	American crows	939:952	American crows (AMCR)	939:959	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	99	from	competence	925:934	arg1	sparrows					968:975	house sparrows	962:975	house sparrows (HOSP)	962:982	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	3	100	theme	amino	602:606	arg1	SYS					648:650	SYS	648:650	SYS	648:650	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	100	theme	amino	602:606	arg1	NYP					633:635	NYP	633:635	NYP	633:635	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	100	theme	amino	602:606	arg1	NYF					638:640	NYF	638:640	NYF	638:640	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	100	theme	amino	602:606	arg1	KYS					653:655	KYS	653:655	KYS	653:655	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	100	theme	amino	602:606	arg1	polymorphisms					613:625	amino acid polymorphisms	602:625	amino acid polymorphisms	602:625	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	100	theme	amino	602:606	arg1	deletion					661:668	deletion	661:668	deletion (A'DEL)	661:676	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	3	100	theme	amino	602:606	arg1	SYP					643:645	SYP	643:645	SYP	643:645	In the present study, amino acid polymorphisms, NYT, NYP, NYF, SYP, SYS, KYS and deletion (A'DEL), were reverse engineered into a parental WNV (NYS) cDNA infectious clone to generate WNV glycosylation mutant viruses.
31306420	2	101	theme	protein	376:382	arg1	patterns					398:405	altered E protein glycosylation patterns	366:405	altered E protein glycosylation patterns	366:405	Naturally occurring isolates with altered E protein glycosylation patterns have been observed in WNV isolates; however, the specific effects of these polymorphisms on avian host pathogenesis and vector competence have not been investigated before.
31306420	6	102	theme	avian	1246:1250	arg1	competence					1265:1274	avian and mosquito competence	1246:1274	avian and mosquito competence	1246:1274	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	5	103	theme	viral	1063:1067	arg1	replication					1069:1079	higher viral replication	1056:1079	higher viral replication	1056:1079	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	8	104	theme	reduced	1489:1495	arg1	competence					1504:1513	reduced vector competence	1489:1513	reduced vector competence	1489:1513	Only NYP showed reduced vector competence in both Cx.
31306420	1	105	link	N-linked	128:135	arg1	motif					151:155	The N-linked glycosylation motif	124:155	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	124:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	0	106	theme	avian	86:90	arg1	virulence					92:100	avian virulence	86:100	avian virulence	86:100	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	0	107	theme	envelope	46:53	arg1	protein					55:61	the West Nile virus envelope protein	26:61	the West Nile virus envelope protein	26:61	N-linked glycosylation of the West Nile virus envelope protein is not a requisite for avian virulence or vector competence.
31306420	5	108	theme	glycosylated	1028:1039	arg1	viruses					1041:1047	NYT glycosylated viruses	1024:1047	NYT glycosylated viruses	1024:1047	The NYS and NYT glycosylated viruses showed higher viral replication, and lower pH and temperature sensitivity than NYP, NYF, SYP, SYS, KYS and A'DEL viruses in vitro.
31306420	11	109	theme	glycosylated	1686:1697	arg1	NYS					1699:1701	glycosylated NYS	1686:1701	glycosylated NYS	1686:1701	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	109	theme	glycosylated	1686:1697	arg1	SYP					1734:1736	SYP	1734:1736	SYP	1734:1736	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	109	theme	glycosylated	1686:1697	arg1	NYF					1729:1731	NYF	1729:1731	NYF	1729:1731	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	109	theme	glycosylated	1686:1697	arg1	NYP					1724:1726	NYP	1724:1726	NYP	1724:1726	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	11	109	theme	glycosylated	1686:1697	arg1	mutants					1746:1752	KYS mutants	1742:1752	KYS mutants	1742:1752	Glycosylated NYT exhibited similar avian virulence properties as NYS, but resulted in higher mosquito oral infectivity than glycosylated NYS and nonglycosylated, NYP, NYF, SYP and KYS mutants.
31306420	6	110	theme	glycosylation	1315:1327	arg1	status					1329:1334	the E-protein glycosylation status	1301:1334	the E-protein glycosylation status	1301:1334	Interestingly, in vivo results demonstrated asymmetric effects in avian and mosquito competence that were independent of the E-protein glycosylation status.
31306420	1	111	theme	E	205:205	arg1	protein					208:214	the envelope (E) protein	191:214	the envelope (E) protein of West Nile virus (WNV)	191:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
31306420	12	112	theme	vector	1857:1862	arg1	phenotypes					1875:1884	differential avian host and vector competence phenotypes	1829:1884	phenotypes	1875:1884	These data demonstrated that amino acid polymorphisms at E154/156 dictate differential avian host and vector competence phenotypes independent of E-protein glycosylation status.
31306420	4	113	theme	house	962:966	arg1	HOSP					978:981	HOSP	978:981	HOSP	978:981	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	4	113	theme	house	962:966	arg1	sparrows					968:975	house sparrows	962:975	house sparrows (HOSP)	962:982	These WNV glycosylation mutant viruses were characterized for in vitro growth, pH-sensitivity, temperature-sensitivity and host competence in American crows (AMCR), house sparrows (HOSP) and Culex quinquefasciatus.
31306420	1	114	theme	protein	208:214	arg1	position					171:178	amino acid position 154-156	160:186	amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV)	160:239	The N-linked glycosylation motif at amino acid position 154-156 of the envelope (E) protein of West Nile virus (WNV) is linked to enhanced murine neuroinvasiveness, avian pathogenicity and vector competence.
29672582	5	0	dep	METHODS	1056:1062	arg1	collected					1067:1075	collected	1067:1075	collected sera from 12 IgG4RD patients and 8 healthy controls	1067:1127	METHODS We collected sera from 12 IgG4RD patients and 8 healthy controls.
29672582	4	1	from	hypocomplementemia	962:979	arg1	IgG4RD					1048:1053	IgG4RD	1048:1053	IgG4RD	1048:1053	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	2	2	theme	complement	584:593	arg1	activation					595:604	complement activation	584:604	complement activation	584:604	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	6	3	theme	IgG	1173:1175	arg1	Kit					1195:1197	Melon™ Gel IgG Spin Purification Kit	1162:1197	Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix	1162:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	1	4	theme	IgG4-related	275:286	arg1	IgG4RD					297:302	IgG4RD	297:302	IgG4RD	297:302	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	4	theme	IgG4-related	275:286	arg1	disease					288:294	IgG4-related disease	275:294	IgG4-related disease (IgG4RD)	275:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	6	5	theme	Melon™	1162:1167	arg1	Kit					1195:1197	Melon™ Gel IgG Spin Purification Kit	1162:1197	Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix	1162:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	3	6	theme	glycans	724:730	arg1	concentration					698:710	the concentration	694:710	the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients	694:785	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	4	7	theme	lymph	1033:1037	arg1	node					1039:1042	lymph node	1033:1042	lymph node	1033:1042	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	4	7	theme	lymph	1033:1037	arg1	kidney					1015:1020	kidney	1015:1020	kidney	1015:1020	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	1	8	theme	increased	183:191	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	8	theme	increased	183:191	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	8	theme	increased	183:191	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	3	9	theme	serum	757:761	arg1	IgG4					763:766	serum IgG4	757:766	serum IgG4	757:766	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	1	10	theme	IgG4	199:202	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	10	theme	IgG4	199:202	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	10	theme	IgG4	199:202	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	12	11	theme	IgG4	2014:2017	arg1	galactosylation					1995:2009	decreased galactosylation	1985:2009	decreased galactosylation of IgG4	1985:2017	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	9	12	dep	galactosylation	1623:1637	arg1	the					1619:1621	the	1619:1621	the	1619:1621	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	14	13	theme	Further	2198:2204	arg1	investigation					2206:2218	Further investigation	2198:2218	Further investigation	2198:2218	Further investigation is needed to clarify the role of IgG4 in IgG4RD.
29672582	4	14	dep	hypocomplementemia	962:979	arg1	pancreas					1023:1030	pancreas	1023:1030	pancreas	1023:1030	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	4	14	dep	hypocomplementemia	962:979	arg1	node					1039:1042	lymph node	1033:1042	lymph node	1033:1042	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	4	14	dep	hypocomplementemia	962:979	arg1	kidney					1015:1020	kidney	1015:1020	kidney	1015:1020	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	2	15	theme	G0	533:534	arg1	N-glycan					536:543	G0 N-glycan	533:543	G0 N-glycan	533:543	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	2	15	theme	G0	533:534	arg1	glycan					525:530	agalactosylated N-linked glycan	500:530	agalactosylated N-linked glycan (G0 N-glycan)	500:544	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	0	16	from	existence	59:67	arg1	patients					127:134	patients	127:134	patients with IgG4-related disease	127:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	6	17	theme	IgG4	1226:1229	arg1	Matrix					1245:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	3	18	link	N-linked	715:722	arg1	N-glycan					733:740	N-glycan	733:740	N-glycan	733:740	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	3	18	link	N-linked	715:722	arg1	glycans					724:730	N-linked glycans	715:730	N-linked glycans (N-glycan) released from serum IgG4	715:766	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	3	19	from	concentration	698:710	arg1	patients					778:785	IgG4RD patients	771:785	IgG4RD patients	771:785	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	1	20	from	events	265:270	arg1	IgG4RD					297:302	IgG4RD	297:302	IgG4RD	297:302	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	20	from	events	265:270	arg1	disease					288:294	IgG4-related disease	275:294	IgG4-related disease (IgG4RD)	275:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	8	21	dep	RESULTS	1322:1328	arg1	observed					1436:1443	observed	1436:1443	were observed in IgG4RD compared with healthy controls	1431:1484	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	6	22	theme	Capture	1211:1217	arg1	Matrix					1245:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	0	23	theme	IgG4-related	141:152	arg1	disease					154:160	IgG4-related disease	141:160	IgG4-related disease	141:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	13	24	theme	IgG4	2122:2125	arg1	change					2140:2145	IgG4 fucosylation change	2122:2145	IgG4 fucosylation change	2122:2145	IgG4 fucosylation change may be related to complement activation in IgG4RD.
29672582	10	25	theme	organ	1808:1812	arg1	involvement					1814:1824	individual organ involvement	1797:1824	individual organ involvement of IgG4RD	1797:1834	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	9	26	theme	IgG4	1657:1660	arg1	N-glycans					1662:1670	IgG4 N-glycans	1657:1670	IgG4 N-glycans	1657:1670	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	4	27	theme	IgG4	913:916	arg1	glycoform					918:926	each IgG4 glycoform	908:926	each IgG4 glycoform	908:926	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	0	28	with	patients	127:134	arg1	disease					154:160	IgG4-related disease	141:160	IgG4-related disease	141:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	1	29	theme	IgG4RD	406:411	arg1	pathogenesis					390:401	the pathogenesis	386:401	the pathogenesis of IgG4RD	386:411	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	4	30	theme	organ	996:1000	arg1	involvement					1002:1012	individual organ involvement	985:1012	individual organ involvement	985:1012	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	8	31	theme	healthy	1469:1475	arg1	controls					1477:1484	healthy controls	1469:1484	healthy controls	1469:1484	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	6	32	theme	Purification	1182:1193	arg1	Kit					1195:1197	Melon™ Gel IgG Spin Purification Kit	1162:1197	Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix	1162:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	5	33	theme	healthy	1112:1118	arg1	controls					1120:1127	8 healthy controls	1110:1127	8 healthy controls	1110:1127	METHODS We collected sera from 12 IgG4RD patients and 8 healthy controls.
29672582	2	34	link	N-linked	516:523	arg1	N-glycan					536:543	G0 N-glycan	533:543	G0 N-glycan	533:543	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	2	34	link	N-linked	516:523	arg1	glycan					525:530	agalactosylated N-linked glycan	500:530	agalactosylated N-linked glycan (G0 N-glycan)	500:544	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	12	35	theme	organ	2093:2097	arg1	involvement					2099:2109	individual organ involvement	2082:2109	individual organ involvement	2082:2109	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	1	36	theme	patients	332:339	arg1	half					317:320	half	317:320	half of IgG4RD patients	317:339	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	37	theme	BACKGROUND	163:172	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	37	theme	BACKGROUND	163:172	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	37	theme	BACKGROUND	163:172	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	0	38	from	Changes	0:6	arg1	N-glycans					11:19	N-glycans	11:19	N-glycans of IgG4	11:27	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	2	39	theme	inflammatory	649:660	arg1	diseases					662:669	various inflammatory diseases	641:669	various inflammatory diseases	641:669	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	8	40	theme	Significant	1330:1340	arg1	increases					1342:1350	Significant increases	1330:1350	Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations	1330:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	3	41	theme	glycosylation	818:830	arg1	changes					832:838	glycosylation changes	818:838	glycosylation changes	818:838	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	0	42	theme	hypocomplementemia	72:89	arg1	existence					59:67	the existence	55:67	the existence of hypocomplementemia	55:89	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	0	42	theme	hypocomplementemia	72:89	arg1	involvement					112:122	individual organ involvement	95:122	individual organ involvement in patients with IgG4-related disease	95:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	5	43	theme	IgG4RD	1090:1095	arg1	patients					1097:1104	12 IgG4RD patients	1087:1104	12 IgG4RD patients	1087:1104	METHODS We collected sera from 12 IgG4RD patients and 8 healthy controls.
29672582	2	44	with	IgG	491:493	arg1	N-glycan					536:543	G0 N-glycan	533:543	G0 N-glycan	533:543	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	2	44	with	IgG	491:493	arg1	glycan					525:530	agalactosylated N-linked glycan	500:530	agalactosylated N-linked glycan (G0 N-glycan)	500:544	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	9	45	theme	glycan	1536:1541	arg1	levels					1518:1523	decreased levels	1508:1523	decreased levels of IgG4 F0 glycan	1508:1541	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	2	46	theme	agalactosylated	500:514	arg1	N-glycan					536:543	G0 N-glycan	533:543	G0 N-glycan	533:543	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	2	46	theme	agalactosylated	500:514	arg1	glycan					525:530	agalactosylated N-linked glycan	500:530	agalactosylated N-linked glycan (G0 N-glycan)	500:544	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	0	47	theme	individual	95:104	arg1	involvement					112:122	individual organ involvement	95:122	individual organ involvement in patients with IgG4-related disease	95:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	8	48	theme	G0	1360:1361	arg1	N-glycan					1363:1370	IgG4 G0 N-glycan	1355:1370	IgG4 G0 N-glycan	1355:1370	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	1	49	from	role	370:373	arg1	pathogenesis					390:401	the pathogenesis	386:401	the pathogenesis of IgG4RD	386:411	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	7	50	theme	Xpress	1302:1307	arg1	methodology					1309:1319	S-BIO GlycanMap® Xpress methodology	1285:1319	S-BIO GlycanMap® Xpress methodology	1285:1319	IgG4 N-glycans were analyzed by S-BIO GlycanMap® Xpress methodology.
29672582	2	51	contain	have	547:550	arg2	roles					568:572	proinflammatory roles	552:572	proinflammatory roles	552:572	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	2	51	contain	have	547:550	arg1	glycosylation					465:477	altered IgG glycosylation	453:477	altered IgG glycosylation	453:477	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	5	52	from	patients	1097:1104	arg1	sera					1077:1080	sera	1077:1080	sera from 12 IgG4RD patients and 8 healthy controls	1077:1127	METHODS We collected sera from 12 IgG4RD patients and 8 healthy controls.
29672582	7	53	theme	S-BIO	1285:1289	arg1	methodology					1309:1319	S-BIO GlycanMap® Xpress methodology	1285:1319	S-BIO GlycanMap® Xpress methodology	1285:1319	IgG4 N-glycans were analyzed by S-BIO GlycanMap® Xpress methodology.
29672582	2	54	theme	IgG	461:463	arg1	glycosylation					465:477	altered IgG glycosylation	453:477	altered IgG glycosylation	453:477	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	13	55	from	activation	2176:2185	arg1	IgG4RD					2190:2195	IgG4RD	2190:2195	IgG4RD	2190:2195	IgG4 fucosylation change may be related to complement activation in IgG4RD.
29672582	8	56	theme	fucosylated	1381:1391	arg1	concentrations					1416:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	0	57	theme	IgG4	24:27	arg1	N-glycans					11:19	N-glycans	11:19	N-glycans of IgG4	11:27	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	5	58	from	controls	1120:1127	arg1	sera					1077:1080	sera	1077:1080	sera from 12 IgG4RD patients and 8 healthy controls	1077:1127	METHODS We collected sera from 12 IgG4RD patients and 8 healthy controls.
29672582	2	59	dep	glycosylation	465:477	arg1	IgG					491:493	IgG	491:493	IgG	491:493	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	8	60	theme	N-glycan	1406:1413	arg1	concentrations					1416:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	0	61	with	Changes	0:6	arg1	existence					59:67	the existence	55:67	the existence of hypocomplementemia	55:89	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	0	61	with	Changes	0:6	arg1	involvement					112:122	individual organ involvement	95:122	individual organ involvement in patients with IgG4-related disease	95:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	3	62	attach	released	743:750	arg2	N-glycan					733:740	N-glycan	733:740	N-glycan	733:740	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	3	62	attach	released	743:750	arg1	IgG4					763:766	serum IgG4	757:766	serum IgG4	757:766	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	3	62	attach	released	743:750	arg2	glycans					724:730	N-linked glycans	715:730	N-linked glycans (N-glycan) released from serum IgG4	715:766	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	8	63	dep	N-glycan	1363:1370	arg1	concentrations					1416:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	1	64	theme	cells	251:255	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	64	theme	cells	251:255	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	64	theme	cells	251:255	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	10	65	theme	IgG4	1748:1751	arg1	N-glycans					1753:1761	IgG4 N-glycans	1748:1761	IgG4 N-glycans	1748:1761	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	0	66	from	involvement	112:122	arg1	patients					127:134	patients	127:134	patients with IgG4-related disease	127:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	14	67	theme	IgG4	2253:2256	arg1	role					2245:2248	the role	2241:2248	the role of IgG4 in IgG4RD	2241:2266	Further investigation is needed to clarify the role of IgG4 in IgG4RD.
29672582	3	68	theme	N-linked	715:722	arg1	N-glycan					733:740	N-glycan	733:740	N-glycan	733:740	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	3	68	theme	N-linked	715:722	arg1	glycans					724:730	N-linked glycans	715:730	N-linked glycans (N-glycan) released from serum IgG4	715:766	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	1	69	theme	key	261:263	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	69	theme	key	261:263	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	69	theme	key	261:263	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	12	70	from	activation	2048:2057	arg1	IgG4RD					2114:2119	IgG4RD	2114:2119	IgG4RD	2114:2119	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	10	71	gly	glycosylation	1731:1743	arg1	N-glycans					1753:1761	IgG4 N-glycans	1748:1761	IgG4 N-glycans	1748:1761	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	9	72	theme	N-glycans	1662:1670	arg1	sialyation					1643:1652	sialyation	1643:1652	sialyation	1643:1652	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	9	72	theme	N-glycans	1662:1670	arg1	galactosylation					1623:1637	galactosylation	1623:1637	galactosylation	1623:1637	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	10	73	from	differences	1712:1722	arg1	glycosylation					1731:1743	the glycosylation	1727:1743	the glycosylation of IgG4 N-glycans	1727:1761	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	6	74	theme	Gel	1169:1171	arg1	Kit					1195:1197	Melon™ Gel IgG Spin Purification Kit	1162:1197	Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix	1162:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	6	75	theme	Affinity	1236:1243	arg1	Matrix					1245:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	10	76	theme	N-glycans	1753:1761	arg1	glycosylation					1731:1743	the glycosylation	1727:1743	the glycosylation of IgG4 N-glycans	1727:1761	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	1	77	theme	Although	174:181	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	77	theme	Although	174:181	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	77	theme	Although	174:181	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	6	78	theme	Hu	1232:1233	arg1	Matrix					1245:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	10	79	theme	individual	1797:1806	arg1	involvement					1814:1824	individual organ involvement	1797:1824	individual organ involvement of IgG4RD	1797:1834	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	1	80	theme	serum	193:197	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	80	theme	serum	193:197	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	80	theme	serum	193:197	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	12	81	theme	decreased	1985:1993	arg1	galactosylation					1995:2009	decreased galactosylation	1985:2009	decreased galactosylation of IgG4	1985:2017	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	11	82	with	patients	1938:1945	arg1	IgG4RD					1952:1957	IgG4RD	1952:1957	IgG4RD	1952:1957	CONCLUSIONS Although IgG4 has anti-inflammatory properties, IgG4 G0 and F1 glycans were increased in patients with IgG4RD.
29672582	4	83	theme	glycoform	918:926	arg1	concentration					891:903	the concentration	887:903	the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD	887:1053	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	9	84	theme	IgG4	1528:1531	arg1	glycan					1536:1541	IgG4 F0 glycan	1528:1541	IgG4 F0 glycan	1528:1541	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	1	85	theme	IgG4	378:381	arg1	role					370:373	the role	366:373	the role of IgG4 in the pathogenesis of IgG4RD	366:411	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	10	86	theme	IgG4RD	1829:1834	arg1	involvement					1814:1824	individual organ involvement	1797:1824	individual organ involvement of IgG4RD	1797:1834	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	1	87	theme	tissue	214:219	arg1	events					265:270	key events	261:270	key events in IgG4-related disease (IgG4RD)	261:303	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	87	theme	tissue	214:219	arg1	level					204:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level	163:208	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	1	87	theme	tissue	214:219	arg1	infiltration					221:232	tissue infiltration	214:232	tissue infiltration	214:232	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	6	88	theme	Select	1219:1224	arg1	Matrix					1245:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	Capture Select IgG4 (Hu) Affinity Matrix	1211:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	13	89	theme	complement	2165:2174	arg1	activation					2176:2185	complement activation	2165:2185	complement activation in IgG4RD	2165:2195	IgG4 fucosylation change may be related to complement activation in IgG4RD.
29672582	4	90	gly	glycoform	918:926	arg1	IgG4					913:916	each IgG4 glycoform	908:926	each IgG4 glycoform	908:926	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	2	91	theme	proinflammatory	552:566	arg1	roles					568:572	proinflammatory roles	552:572	proinflammatory roles	552:572	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	12	92	theme	involvement	2099:2109	arg1	activation					2048:2057	complement activation	2037:2057	complement activation	2037:2057	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	12	92	theme	involvement	2099:2109	arg1	differences					2067:2077	the differences	2063:2077	the differences of individual organ involvement in IgG4RD	2063:2119	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	3	93	theme	IgG4RD	771:776	arg1	patients					778:785	IgG4RD patients	771:785	IgG4RD patients	771:785	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	13	94	theme	fucosylation	2127:2138	arg1	change					2140:2145	IgG4 fucosylation change	2122:2145	IgG4 fucosylation change	2122:2145	IgG4 fucosylation change may be related to complement activation in IgG4RD.
29672582	8	95	located	observed	1436:1443	arg1	IgG4RD					1448:1453	IgG4RD	1448:1453	IgG4RD	1448:1453	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	8	95	located	observed	1436:1443	arg2	increases					1342:1350	Significant increases	1330:1350	Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations	1330:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	9	96	theme	decreased	1508:1516	arg1	levels					1518:1523	decreased levels	1508:1523	decreased levels of IgG4 F0 glycan	1508:1541	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	3	97	theme	healthy	852:858	arg1	controls					860:867	healthy controls	852:867	healthy controls	852:867	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	4	98	theme	individual	985:994	arg1	involvement					1002:1012	individual organ involvement	985:1012	individual organ involvement	985:1012	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	6	99	theme	Spin	1177:1180	arg1	Kit					1195:1197	Melon™ Gel IgG Spin Purification Kit	1162:1197	Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix	1162:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	6	100	attach	isolated	1139:1146	arg2	IgG4					1130:1133	IgG4	1130:1133	IgG4	1130:1133	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	6	100	attach	isolated	1139:1146	arg1	sera					1153:1156	sera	1153:1156	sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix	1153:1250	IgG4 was isolated from sera via Melon™ Gel IgG Spin Purification Kit followed by Capture Select IgG4 (Hu) Affinity Matrix.
29672582	1	101	theme	IgG4RD	325:330	arg1	patients					332:339	IgG4RD patients	325:339	IgG4RD patients	325:339	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	12	102	from	differences	2067:2077	arg1	IgG4RD					2114:2119	IgG4RD	2114:2119	IgG4RD	2114:2119	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	2	103	theme	diseases	662:669	arg1	pathogenesis					625:636	the pathogenesis	621:636	the pathogenesis of various inflammatory diseases	621:669	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	12	104	theme	individual	2082:2091	arg1	involvement					2099:2109	individual organ involvement	2082:2109	individual organ involvement	2082:2109	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	9	105	theme	F0	1533:1534	arg1	glycan					1536:1541	IgG4 F0 glycan	1528:1541	IgG4 F0 glycan	1528:1541	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	14	106	from	role	2245:2248	arg1	IgG4RD					2261:2266	IgG4RD	2261:2266	IgG4RD	2261:2266	Further investigation is needed to clarify the role of IgG4 in IgG4RD.
29672582	2	107	theme	N-linked	516:523	arg1	N-glycan					536:543	G0 N-glycan	533:543	G0 N-glycan	533:543	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	2	107	theme	N-linked	516:523	arg1	glycan					525:530	agalactosylated N-linked glycan	500:530	agalactosylated N-linked glycan (G0 N-glycan)	500:544	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	0	108	from	relationship	37:48	arg1	N-glycans					11:19	N-glycans	11:19	N-glycans of IgG4	11:27	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	2	109	theme	various	641:647	arg1	diseases					662:669	various inflammatory diseases	641:669	various inflammatory diseases	641:669	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	3	110	theme	changes	832:838	arg1	difference					804:813	the difference	800:813	the difference of glycosylation changes to those in healthy controls	800:867	This study determined the concentration of N-linked glycans (N-glycan) released from serum IgG4 in IgG4RD patients and compared the difference of glycosylation changes to those in healthy controls.
29672582	0	111	theme	organ	106:110	arg1	involvement					112:122	individual organ involvement	95:122	individual organ involvement in patients with IgG4-related disease	95:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	4	112	from	involvement	1002:1012	arg1	IgG4RD					1048:1053	IgG4RD	1048:1053	IgG4RD	1048:1053	We also compared the concentration of each IgG4 glycoform between patients with and without hypocomplementemia and individual organ involvement (kidney, pancreas, lymph node) in IgG4RD.
29672582	11	113	dep	IgG4	1858:1861	arg1	has					1863:1865	has	1863:1865	has anti-inflammatory properties	1863:1894	CONCLUSIONS Although IgG4 has anti-inflammatory properties, IgG4 G0 and F1 glycans were increased in patients with IgG4RD.
29672582	11	113	dep	IgG4	1858:1861	arg1	glycans					1912:1918	glycans	1912:1918	glycans	1912:1918	CONCLUSIONS Although IgG4 has anti-inflammatory properties, IgG4 G0 and F1 glycans were increased in patients with IgG4RD.
29672582	11	114	dep	IgG4	1897:1900	arg1	G0					1902:1903	G0	1902:1903	IgG4 G0	1897:1903	CONCLUSIONS Although IgG4 has anti-inflammatory properties, IgG4 G0 and F1 glycans were increased in patients with IgG4RD.
29672582	7	115	theme	GlycanMap®	1291:1300	arg1	methodology					1309:1319	S-BIO GlycanMap® Xpress methodology	1285:1319	S-BIO GlycanMap® Xpress methodology	1285:1319	IgG4 N-glycans were analyzed by S-BIO GlycanMap® Xpress methodology.
29672582	2	116	theme	Many	430:433	arg1	reports					435:441	Many reports	430:441	Many reports	430:441	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	8	117	theme	IgG4	1355:1358	arg1	N-glycan					1363:1370	IgG4 G0 N-glycan	1355:1370	IgG4 G0 N-glycan	1355:1370	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	9	118	from	differences	1604:1614	arg1	sialyation					1643:1652	sialyation	1643:1652	sialyation	1643:1652	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	9	118	from	differences	1604:1614	arg1	galactosylation					1623:1637	galactosylation	1623:1637	galactosylation	1623:1637	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	8	119	theme	N-glycan	1363:1370	arg1	increases					1342:1350	Significant increases	1330:1350	Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations	1330:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	2	120	theme	altered	453:459	arg1	glycosylation					465:477	altered IgG glycosylation	453:477	altered IgG glycosylation	453:477	Many reports show that altered IgG glycosylation, especially IgG with agalactosylated N-linked glycan (G0 N-glycan), have proinflammatory roles including complement activation, implicated in the pathogenesis of various inflammatory diseases.
29672582	8	121	theme	IgG4	1376:1379	arg1	increases					1342:1350	Significant increases	1330:1350	Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations	1330:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	1	122	theme	IgG4-positive	237:249	arg1	cells					251:255	IgG4-positive cells	237:255	IgG4-positive cells	237:255	BACKGROUND Although increased serum IgG4 level and tissue infiltration of IgG4-positive cells are key events in IgG4-related disease (IgG4RD), and nearly half of IgG4RD patients show hypocomplementemia, the role of IgG4 in the pathogenesis of IgG4RD remains unclear.
29672582	12	123	theme	complement	2037:2046	arg1	activation					2048:2057	complement activation	2037:2057	complement activation	2037:2057	Our results suggest that decreased galactosylation of IgG4 is not related to complement activation and the differences of individual organ involvement in IgG4RD.
29672582	9	124	theme	significant	1592:1602	arg1	differences					1604:1614	no significant differences	1589:1614	no significant differences in the galactosylation and sialyation of IgG4 N-glycans	1589:1670	Although we observed decreased levels of IgG4 F0 glycan in IgG4RD with hypocomplementemia, there were no significant differences in the galactosylation and sialyation of IgG4 N-glycans.
29672582	7	125	theme	IgG4	1253:1256	arg1	N-glycans					1258:1266	IgG4 N-glycans	1253:1266	IgG4 N-glycans	1253:1266	IgG4 N-glycans were analyzed by S-BIO GlycanMap® Xpress methodology.
29672582	8	126	theme	N-glycan	1393:1400	arg1	concentrations					1416:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	10	127	theme	significant	1700:1710	arg1	differences					1712:1722	no significant differences	1697:1722	no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD	1697:1834	Furthermore, there were no significant differences in the glycosylation of IgG4 N-glycans between patients with and without individual organ involvement of IgG4RD.
29672582	8	128	theme	F1	1403:1404	arg1	concentrations					1416:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29672582	0	129	with	relationship	37:48	arg1	existence					59:67	the existence	55:67	the existence of hypocomplementemia	55:89	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	0	129	with	relationship	37:48	arg1	involvement					112:122	individual organ involvement	95:122	individual organ involvement in patients with IgG4-related disease	95:160	Changes in N-glycans of IgG4 and its relationship with the existence of hypocomplementemia and individual organ involvement in patients with IgG4-related disease.
29672582	11	130	theme	anti-inflammatory	1867:1883	arg1	properties					1885:1894	anti-inflammatory properties	1867:1894	anti-inflammatory properties	1867:1894	CONCLUSIONS Although IgG4 has anti-inflammatory properties, IgG4 G0 and F1 glycans were increased in patients with IgG4RD.
29672582	8	131	gly	fucosylated	1381:1391	arg1	concentrations					1416:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	fucosylated N-glycan (F1 N-glycan) concentrations	1381:1429	RESULTS Significant increases of IgG4 G0 N-glycan and IgG4 fucosylated N-glycan (F1 N-glycan) concentrations were observed in IgG4RD compared with healthy controls.
29954945	0	0	theme	hypertensive	103:114	arg1	rats					116:119	spontaneously hypertensive rats	89:119	spontaneously hypertensive rats	89:119	O-GlcNAcylation reduces proximal tubule protein reabsorption and promotes proteinuria in spontaneously hypertensive rats.
29954945	5	1	theme	renal	595:599	arg1	damage					601:606	renal damage	595:606	renal damage	595:606	We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension.
29954945	5	1	theme	renal	595:599	arg1	development					620:630	development	620:630	development of proteinuria	620:645	We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension.
29954945	1	2	theme	chronic	182:188	arg1	CKD					206:208	CKD	206:208	CKD	206:208	Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD).
29954945	1	2	theme	chronic	182:188	arg1	disease					197:203	chronic kidney disease	182:203	chronic kidney disease (CKD)	182:209	Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD).
29954945	6	3	theme	hypertensive	702:713	arg1	SHR					720:722	SHR	720:722	SHR	720:722	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	6	3	theme	hypertensive	702:713	arg1	rat					715:717	the spontaneously hypertensive rat	684:717	the spontaneously hypertensive rat (SHR) model	684:729	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	9	4	theme	vivo	1360:1363	arg1	conclusion					1368:1377	vivo In conclusion	1360:1377	vivo In conclusion	1360:1377	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	4	5	theme	vascular	435:442	arg1	dysfunction					444:454	vascular dysfunction	435:454	vascular dysfunction	435:454	Cardiac and vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in hypertensive models.
29954945	1	6	theme	kidney	190:195	arg1	CKD					206:208	CKD	206:208	CKD	206:208	Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD).
29954945	1	6	theme	kidney	190:195	arg1	disease					197:203	chronic kidney disease	182:203	chronic kidney disease (CKD)	182:209	Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD).
29954945	9	7	theme	tubule	1133:1138	arg1	line					1145:1148	a proximal tubule cell line	1122:1148	a proximal tubule cell line	1122:1148	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	5	8	gly	O-GlcNAcylation	559:573	arg1	damage					601:606	renal damage	595:606	renal damage	595:606	We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension.
29954945	5	8	gly	O-GlcNAcylation	559:573	arg1	development					620:630	development	620:630	development of proteinuria	620:645	We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension.
29954945	7	9	located	observed	946:953	arg2	this					937:940	this	937:940	this	937:940	Interestingly, this was observed in hypertensive, but not pre-hypertensive, rats.
29954945	7	9	located	observed	946:953	arg1	rats					998:1001	hypertensive, but not pre-hypertensive, rats	958:1001	hypertensive, but not pre-hypertensive, rats	958:1001	Interestingly, this was observed in hypertensive, but not pre-hypertensive, rats.
29954945	8	10	theme	renal	1049:1053	arg1	O-GlcNAcylation					1062:1076	renal cortex O-GlcNAcylation	1049:1076	renal cortex O-GlcNAcylation	1049:1076	Pharmacological inhibition of GFAT decreased renal cortex O-GlcNAcylation, proteinuria, and albuminuria in SHR.
29954945	6	11	theme	glutamine-fructose	781:798	arg1	GFAT					818:821	GFAT	818:821	GFAT	818:821	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	6	11	theme	glutamine-fructose	781:798	arg1	aminotransferase					800:815	glutamine-fructose aminotransferase	781:815	glutamine-fructose aminotransferase (GFAT)	781:822	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	8	12	theme	GFAT	1034:1037	arg1	inhibition					1020:1029	Pharmacological inhibition	1004:1029	Pharmacological inhibition of GFAT	1004:1037	Pharmacological inhibition of GFAT decreased renal cortex O-GlcNAcylation, proteinuria, and albuminuria in SHR.
29954945	4	13	theme	hypertensive	517:528	arg1	models					530:535	hypertensive models	517:535	hypertensive models	517:535	Cardiac and vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in hypertensive models.
29954945	6	14	theme	protein	856:862	arg1	expression					864:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	6	15	theme	O-GlcNAcylation	764:778	arg1	expression					864:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	3	16	theme	hypertensive	370:381	arg1	conditions					383:392	hypertensive conditions	370:392	hypertensive conditions	370:392	However, the mechanisms underlying the development of proteinuria in hypertensive conditions are incompletely understood.
29954945	6	17	theme	cortex	757:762	arg1	O-GlcNAcylation					764:778	renal cortex O-GlcNAcylation	751:778	renal cortex O-GlcNAcylation	751:778	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	5	18	theme	proteinuria	635:645	arg1	damage					601:606	renal damage	595:606	renal damage	595:606	We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension.
29954945	5	18	theme	proteinuria	635:645	arg1	development					620:630	development	620:630	development of proteinuria	620:645	We hypothesized that O-GlcNAcylation is also involved in renal damage, especially development of proteinuria, associated with hypertension.
29954945	6	19	theme	renal	751:755	arg1	O-GlcNAcylation					764:778	renal cortex O-GlcNAcylation	751:778	renal cortex O-GlcNAcylation	751:778	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	9	20	theme	proximal	1124:1131	arg1	line					1145:1148	a proximal tubule cell line	1122:1148	a proximal tubule cell line	1122:1148	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	6	21	theme	higher	744:749	arg1	expression					864:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	0	22	theme	tubule	33:38	arg1	reabsorption					48:59	proximal tubule protein reabsorption	24:59	proximal tubule protein reabsorption	24:59	O-GlcNAcylation reduces proximal tubule protein reabsorption and promotes proteinuria in spontaneously hypertensive rats.
29954945	6	23	theme	transferase	838:848	arg1	expression					864:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	1	24	theme	Hypertensive	122:133	arg1	individuals					135:145	Hypertensive individuals	122:145	Hypertensive individuals	122:145	Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD).
29954945	8	25	theme	cortex	1055:1060	arg1	O-GlcNAcylation					1062:1076	renal cortex O-GlcNAcylation	1049:1076	renal cortex O-GlcNAcylation	1049:1076	Pharmacological inhibition of GFAT decreased renal cortex O-GlcNAcylation, proteinuria, and albuminuria in SHR.
29954945	0	26	theme	proximal	24:31	arg1	reabsorption					48:59	proximal tubule protein reabsorption	24:59	proximal tubule protein reabsorption	24:59	O-GlcNAcylation reduces proximal tubule protein reabsorption and promotes proteinuria in spontaneously hypertensive rats.
29954945	9	27	theme	new	1406:1408	arg1	mechanism					1410:1418	a new mechanism	1404:1418	a new mechanism involved in hypertension-associated proteinuria	1404:1466	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	4	28	from	pathway	506:512	arg1	models					530:535	hypertensive models	517:535	hypertensive models	517:535	Cardiac and vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in hypertensive models.
29954945	4	29	theme	O-GlcNAcylation	490:504	arg1	pathway					506:512	the O-GlcNAcylation pathway	486:512	the O-GlcNAcylation pathway in hypertensive models	486:535	Cardiac and vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in hypertensive models.
29954945	0	30	theme	protein	40:46	arg1	reabsorption					48:59	proximal tubule protein reabsorption	24:59	proximal tubule protein reabsorption	24:59	O-GlcNAcylation reduces proximal tubule protein reabsorption and promotes proteinuria in spontaneously hypertensive rats.
29954945	7	31	theme	hypertensive	958:969	arg1	rats					998:1001	hypertensive, but not pre-hypertensive, rats	958:1001	hypertensive, but not pre-hypertensive, rats	958:1001	Interestingly, this was observed in hypertensive, but not pre-hypertensive, rats.
29954945	6	32	theme	O-GlcNAc	829:836	arg1	OGT					851:853	OGT	851:853	OGT	851:853	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	6	32	theme	O-GlcNAc	829:836	arg1	transferase					838:848	O-GlcNAc transferase	829:848	O-GlcNAc transferase (OGT)	829:854	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	0	33	from	proteinuria	74:84	arg1	rats					116:119	spontaneously hypertensive rats	89:119	spontaneously hypertensive rats	89:119	O-GlcNAcylation reduces proximal tubule protein reabsorption and promotes proteinuria in spontaneously hypertensive rats.
29954945	9	34	theme	surface	1210:1216	arg1	expression					1218:1227	megalin surface expression	1202:1227	megalin surface expression	1202:1227	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	9	35	theme	In	1365:1366	arg1	conclusion					1368:1377	vivo In conclusion	1360:1377	vivo In conclusion	1360:1377	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	9	36	theme	hypertension-associated	1432:1454	arg1	proteinuria					1456:1466	hypertension-associated proteinuria	1432:1466	hypertension-associated proteinuria	1432:1466	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	4	37	from	changes	475:481	arg1	pathway					506:512	the O-GlcNAcylation pathway	486:512	the O-GlcNAcylation pathway in hypertensive models	486:535	Cardiac and vascular dysfunction is associated with changes in the O-GlcNAcylation pathway in hypertensive models.
29954945	8	38	theme	Pharmacological	1004:1018	arg1	inhibition					1020:1029	Pharmacological inhibition	1004:1029	Pharmacological inhibition of GFAT	1004:1037	Pharmacological inhibition of GFAT decreased renal cortex O-GlcNAcylation, proteinuria, and albuminuria in SHR.
29954945	3	39	from	development	340:350	arg1	conditions					383:392	hypertensive conditions	370:392	hypertensive conditions	370:392	However, the mechanisms underlying the development of proteinuria in hypertensive conditions are incompletely understood.
29954945	1	40	theme	greater	154:160	arg1	risk					162:165	greater risk	154:165	greater risk for developing chronic kidney disease (CKD)	154:209	Hypertensive individuals are at greater risk for developing chronic kidney disease (CKD).
29954945	7	41	theme	pre-hypertensive	980:995	arg1	rats					998:1001	hypertensive, but not pre-hypertensive, rats	958:1001	hypertensive, but not pre-hypertensive, rats	958:1001	Interestingly, this was observed in hypertensive, but not pre-hypertensive, rats.
29954945	9	42	theme	megalin	1202:1208	arg1	expression					1218:1227	megalin surface expression	1202:1227	megalin surface expression	1202:1227	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	9	43	theme	albumin	1233:1239	arg1	endocytosis					1241:1251	albumin endocytosis	1233:1251	albumin endocytosis	1233:1251	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	9	44	theme	increased	1168:1176	arg1	O-GlcNAcylation					1178:1192	increased O-GlcNAcylation	1168:1192	increased O-GlcNAcylation	1168:1192	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	9	45	theme	cell	1140:1143	arg1	line					1145:1148	a proximal tubule cell line	1122:1148	a proximal tubule cell line	1122:1148	Using a proximal tubule cell line, we observed that increased O-GlcNAcylation reduced megalin surface expression and albumin endocytosis in vitro, and the effects were correlated in vivo Moreover, megalin is O-GlcNAcylated both in vitro and in vivo In conclusion, our results demonstrate a new mechanism involved in hypertension-associated proteinuria.
29954945	2	46	theme	therapeutic	266:276	arg1	approach					278:285	a possible therapeutic approach	255:285	a possible therapeutic approach to treat CKD	255:298	Reducing proteinuria has been suggested as a possible therapeutic approach to treat CKD.
29954945	3	47	theme	proteinuria	355:365	arg1	development					340:350	the development	336:350	the development of proteinuria in hypertensive conditions	336:392	However, the mechanisms underlying the development of proteinuria in hypertensive conditions are incompletely understood.
29954945	2	48	theme	possible	257:264	arg1	approach					278:285	a possible therapeutic approach	255:285	a possible therapeutic approach to treat CKD	255:298	Reducing proteinuria has been suggested as a possible therapeutic approach to treat CKD.
29954945	6	49	theme	aminotransferase	800:815	arg1	expression					864:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression	744:873	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
29954945	6	50	theme	rat	715:717	arg1	model					725:729	the spontaneously hypertensive rat (SHR) model	684:729	the spontaneously hypertensive rat (SHR) model	684:729	Using the spontaneously hypertensive rat (SHR) model, we observed higher renal cortex O-GlcNAcylation, glutamine-fructose aminotransferase (GFAT), and O-GlcNAc transferase (OGT) protein expression, which positively correlated with proteinuria.
31156631	19	0	theme	IgE	1699:1701	arg1	development					1669:1679	the development	1665:1679	the development of α-gal-specific IgE and hypersensitivity reactions in humans	1665:1742	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	20	1	theme	current	1779:1785	arg1	paradigm					1800:1807	the current food allergy paradigm	1775:1807	the current food allergy paradigm	1775:1807	Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
31156631	16	2	theme	salivary	1415:1422	arg1	analysis					1405:1412	the glycan analysis	1394:1412	the glycan analysis	1394:1412	Consistent with the glycan analysis, salivary samples from Am.
31156631	16	2	theme	salivary	1415:1422	arg1	samples					1424:1430	salivary samples	1415:1430	salivary samples from Am	1415:1438	Consistent with the glycan analysis, salivary samples from Am.
31156631	20	3	theme	Alpha-Gal	1745:1753	arg1	syndrome					1755:1762	Alpha-Gal syndrome	1745:1762	Alpha-Gal syndrome	1745:1762	Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
31156631	19	4	theme	hypersensitivity	1707:1722	arg1	reactions					1724:1732	hypersensitivity reactions	1707:1732	hypersensitivity reactions	1707:1732	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	2	5	from	presence	317:324	arg1	species					348:354	four tick species	338:354	four tick species	338:354	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	scapularis					525:534	Ixodes scapularis	518:534	Ixodes scapularis	518:534	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	americanum					387:396	Amblyomma americanum	377:396	Amblyomma americanum	377:396	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	tick					460:463	the American dog tick	443:463	the American dog tick (Dermacentor variabilis)	443:488	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	maculatum					431:439	Amblyomma maculatum	421:439	Amblyomma maculatum	421:439	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	tick					371:374	the lone-star tick	357:374	the lone-star tick (Amblyomma americanum)	357:397	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	variabilis					478:487	Dermacentor variabilis	466:487	Dermacentor variabilis	466:487	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	tick					512:515	the black-legged tick	495:515	the black-legged tick (Ixodes scapularis)	495:535	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	5	from	presence	317:324	arg1	tick					415:418	the Gulf-Coast tick	400:418	the Gulf-Coast tick (Amblyomma maculatum)	400:440	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	9	6	theme	moieties	935:942	arg1	Immunolocalization					907:924	Immunolocalization	907:924	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini	907:999	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	2	7	theme	Dermacentor	466:476	arg1	variabilis					478:487	Dermacentor variabilis	466:487	Dermacentor variabilis	466:487	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	7	theme	Dermacentor	466:476	arg1	tick					460:463	the American dog tick	443:463	the American dog tick (Dermacentor variabilis)	443:488	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	20	8	theme	allergy	1792:1798	arg1	paradigm					1800:1807	the current food allergy paradigm	1775:1807	the current food allergy paradigm	1775:1807	Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
31156631	18	9	theme	α-gal	1530:1534	arg1	subjects					1545:1552	α-gal allergic subjects	1530:1552	α-gal allergic subjects	1530:1552	scapularis stimulated activation of basophils primed with plasma from α-gal allergic subjects.
31156631	1	10	theme	tick	218:221	arg1	bites					223:227	the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	153:227	bites	223:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	2	11	theme	black-legged	499:510	arg1	tick					512:515	the black-legged tick	495:515	the black-legged tick (Ixodes scapularis)	495:535	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	11	theme	black-legged	499:510	arg1	scapularis					525:534	Ixodes scapularis	518:534	Ixodes scapularis	518:534	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	9	12	theme	secretory	960:968	arg1	vesicles					970:977	the salivary secretory vesicles	947:977	the salivary secretory vesicles of the salivary acini	947:999	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	1	13	theme	IgE	135:137	arg1	antibodies					139:148	specific IgE antibodies	126:148	specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	126:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	9	14	theme	salivary	986:993	arg1	acini					995:999	the salivary acini	982:999	the salivary acini	982:999	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	8	15	link	N-linked	847:854	arg1	proteins					873:880	N-linked α-gal-containing proteins	847:880	N-linked α-gal-containing proteins	847:880	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	1	16	theme	oligosaccharide	157:171	arg1	bites					223:227	the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	153:227	bites	223:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	19	17	theme	tick	1617:1620	arg1	species					1622:1628	certain tick species	1609:1628	certain tick species	1609:1628	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	0	18	from	Discovery	0:8	arg1	Species					66:72	North American Tick Species	46:72	North American Tick Species	46:72	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
31156631	11	19	theme	α-gal	1199:1203	arg1	source					1185:1190	the source	1181:1190	the source of the α-gal	1181:1203	americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal.
31156631	2	20	theme	immunoproteomic	563:577	arg1	approach					579:586	immunoproteomic approach	563:586	immunoproteomic approach	563:586	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	18	21	theme	basophils	1496:1504	arg1	activation					1482:1491	activation	1482:1491	activation of basophils primed with plasma from α-gal allergic subjects	1482:1552	scapularis stimulated activation of basophils primed with plasma from α-gal allergic subjects.
31156631	0	22	theme	Red	93:95	arg1	Allergy					102:108	Red Meat Allergy	93:108	Red Meat Allergy	93:108	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
31156631	8	23	theme	PNGase	795:800	arg1	treatment					804:812	PNGase F treatment	795:812	PNGase F treatment	795:812	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	2	24	theme	American	447:454	arg1	variabilis					478:487	Dermacentor variabilis	466:487	Dermacentor variabilis	466:487	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	24	theme	American	447:454	arg1	tick					460:463	the American dog tick	443:463	the American dog tick (Dermacentor variabilis)	443:488	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	12	25	link	N-linked	1206:1213	arg1	analysis					1222:1229	N-linked glycan analysis	1206:1229	N-linked glycan analysis	1206:1229	N-linked glycan analysis revealed that Am.
31156631	15	26	contain	contains	1345:1352	arg1	maculatum					1335:1343	maculatum	1335:1343	maculatum	1335:1343	maculatum contains no detectable quantity.
31156631	15	26	contain	contains	1345:1352	arg2	quantity					1368:1375	no detectable quantity	1354:1375	no detectable quantity	1354:1375	maculatum contains no detectable quantity.
31156631	2	27	theme	carbohydrate	593:604	arg1	analysis					606:613	carbohydrate analysis	593:613	carbohydrate analysis	593:613	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	9	28	theme	α-gal-containing	1040:1055	arg1	antigens					1057:1064	α-gal-containing antigens	1040:1064	α-gal-containing antigens in ticks	1040:1073	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	2	29	theme	tick	343:346	arg1	species					348:354	four tick species	338:354	four tick species	338:354	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	11	30	theme	silicone	1143:1150	arg1	system					1161:1166	a silicone membrane system	1141:1166	a silicone membrane system to determine the source of the α-gal	1141:1203	americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal.
31156631	0	31	theme	Alpha-Gal-Containing	13:32	arg1	Antigens					34:41	Alpha-Gal-Containing Antigens	13:41	Alpha-Gal-Containing Antigens	13:41	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
31156631	1	32	theme	meat	268:271	arg1	allergy					273:279	red meat allergy	264:279	red meat allergy	264:279	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	11	33	theme	membrane	1152:1159	arg1	system					1161:1166	a silicone membrane system	1141:1166	a silicone membrane system to determine the source of the α-gal	1141:1203	americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal.
31156631	9	34	from	ticks	1069:1073	arg1	nature					1030:1035	the secretory nature	1016:1035	the secretory nature of α-gal-containing antigens in ticks	1016:1073	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	2	35	theme	lone-star	361:369	arg1	tick					371:374	the lone-star tick	357:374	the lone-star tick (Amblyomma americanum)	357:397	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	35	theme	lone-star	361:369	arg1	americanum					387:396	Amblyomma americanum	377:396	Amblyomma americanum	377:396	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	8	36	theme	α-gal-containing	856:871	arg1	proteins					873:880	N-linked α-gal-containing proteins	847:880	N-linked α-gal-containing proteins	847:880	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	12	37	theme	N-linked	1206:1213	arg1	analysis					1222:1229	N-linked glycan analysis	1206:1229	N-linked glycan analysis	1206:1229	N-linked glycan analysis revealed that Am.
31156631	2	38	theme	Gulf-Coast	404:413	arg1	tick					415:418	the Gulf-Coast tick	400:418	the Gulf-Coast tick (Amblyomma maculatum)	400:440	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	38	theme	Gulf-Coast	404:413	arg1	maculatum					431:439	Amblyomma maculatum	421:439	Amblyomma maculatum	421:439	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	9	39	from	antigens	1057:1064	arg1	ticks					1069:1073	ticks	1069:1073	ticks	1069:1073	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	11	40	dep	blood	1115:1119	arg1	lacks					1122:1126	lacks	1122:1126	lacks α-gal	1122:1132	americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal.
31156631	0	41	theme	American	52:59	arg1	Species					66:72	North American Tick Species	46:72	North American Tick Species	46:72	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
31156631	8	42	gly	deglycosylation	828:842	arg1	proteins					873:880	N-linked α-gal-containing proteins	847:880	N-linked α-gal-containing proteins	847:880	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	8	42	gly	deglycosylation	828:842	arg1	glands					899:904	tick salivary glands	885:904	tick salivary glands	885:904	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	16	43	from	Am	1437:1438	arg1	analysis					1405:1412	the glycan analysis	1394:1412	the glycan analysis	1394:1412	Consistent with the glycan analysis, salivary samples from Am.
31156631	16	43	from	Am	1437:1438	arg1	samples					1424:1430	salivary samples	1415:1430	salivary samples from Am	1415:1438	Consistent with the glycan analysis, salivary samples from Am.
31156631	11	44	theme	human	1109:1113	arg1	blood					1115:1119	human blood	1109:1119	human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal	1109:1203	americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal.
31156631	8	45	theme	salivary	890:897	arg1	glands					899:904	tick salivary glands	885:904	tick salivary glands	885:904	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	16	46	theme	glycan	1398:1403	arg1	analysis					1405:1412	the glycan analysis	1394:1412	the glycan analysis	1394:1412	Consistent with the glycan analysis, salivary samples from Am.
31156631	16	46	theme	glycan	1398:1403	arg1	samples					1424:1430	salivary samples	1415:1430	salivary samples from Am	1415:1438	Consistent with the glycan analysis, salivary samples from Am.
31156631	19	47	theme	α-gal-specific	1684:1697	arg1	IgE					1699:1701	α-gal-specific IgE	1684:1701	α-gal-specific IgE	1684:1701	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	20	48	theme	food	1787:1790	arg1	paradigm					1800:1807	the current food allergy paradigm	1775:1807	the current food allergy paradigm	1775:1807	Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
31156631	2	49	attach	presence	317:324	arg1	species					348:354	four tick species	338:354	four tick species	338:354	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	scapularis					525:534	Ixodes scapularis	518:534	Ixodes scapularis	518:534	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	americanum					387:396	Amblyomma americanum	377:396	Amblyomma americanum	377:396	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	tick					460:463	the American dog tick	443:463	the American dog tick (Dermacentor variabilis)	443:488	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	maculatum					431:439	Amblyomma maculatum	421:439	Amblyomma maculatum	421:439	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	tick					371:374	the lone-star tick	357:374	the lone-star tick (Amblyomma americanum)	357:397	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	variabilis					478:487	Dermacentor variabilis	466:487	Dermacentor variabilis	466:487	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	tick					512:515	the black-legged tick	495:515	the black-legged tick (Ixodes scapularis)	495:535	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg2	α-gal					329:333	α-gal	329:333	α-gal	329:333	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	49	attach	presence	317:324	arg1	tick					415:418	the Gulf-Coast tick	400:418	the Gulf-Coast tick (Amblyomma maculatum)	400:440	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	50	theme	Ixodes	518:523	arg1	tick					512:515	the black-legged tick	495:515	the black-legged tick (Ixodes scapularis)	495:535	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	50	theme	Ixodes	518:523	arg1	scapularis					525:534	Ixodes scapularis	518:534	Ixodes scapularis	518:534	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	3	51	theme	Anti-α-gal	616:625	arg1	antibodies					627:636	Anti-α-gal antibodies	616:636	Anti-α-gal antibodies	616:636	Anti-α-gal antibodies identified α-gal in the salivary glands of both Am.
31156631	19	52	theme	reactions	1724:1732	arg1	development					1669:1679	the development	1665:1679	the development of α-gal-specific IgE and hypersensitivity reactions in humans	1665:1742	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	14	53	from	saliva	1299:1304	arg1	α-gal					1284:1288	α-gal	1284:1288	α-gal	1284:1288	scapularis have α-gal in their saliva and salivary glands, but Am.
31156631	3	54	theme	salivary	662:669	arg1	glands					671:676	the salivary glands	658:676	the salivary glands of both Am	658:687	Anti-α-gal antibodies identified α-gal in the salivary glands of both Am.
31156631	1	55	theme	galactose-α-1	173:185	arg1	bites					223:227	the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	153:227	bites	223:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	14	56	theme	salivary	1310:1317	arg1	glands					1319:1324	salivary glands	1310:1324	salivary glands	1310:1324	scapularis have α-gal in their saliva and salivary glands, but Am.
31156631	9	57	theme	α-gal	929:933	arg1	moieties					935:942	α-gal moieties	929:942	α-gal moieties	929:942	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	3	58	theme	Am	686:687	arg1	glands					671:676	the salivary glands	658:676	the salivary glands of both Am	658:687	Anti-α-gal antibodies identified α-gal in the salivary glands of both Am.
31156631	1	59	theme	α-gal	201:205	arg1	bites					223:227	the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	153:227	bites	223:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	15	60	theme	detectable	1357:1366	arg1	quantity					1368:1375	no detectable quantity	1354:1375	no detectable quantity	1354:1375	maculatum contains no detectable quantity.
31156631	18	61	theme	allergic	1536:1543	arg1	subjects					1545:1552	α-gal allergic subjects	1530:1552	α-gal allergic subjects	1530:1552	scapularis stimulated activation of basophils primed with plasma from α-gal allergic subjects.
31156631	1	62	theme	following	208:216	arg1	bites					223:227	the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	153:227	bites	223:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	1	63	dep	bites	223:227	arg1	3-galactose					188:198	the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	153:227	3-galactose	188:198	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	9	64	theme	salivary	951:958	arg1	vesicles					970:977	the salivary secretory vesicles	947:977	the salivary secretory vesicles of the salivary acini	947:999	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	19	65	from	species	1622:1628	arg1	bites					1598:1602	bites	1598:1602	bites from certain tick species	1598:1628	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	1	66	theme	specific	126:133	arg1	antibodies					139:148	specific IgE antibodies	126:148	specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	126:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	8	67	from	deglycosylation	828:842	arg1	glands					899:904	tick salivary glands	885:904	tick salivary glands	885:904	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	1	68	theme	antibodies	139:148	arg1	Development					111:121	Development	111:121	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	111:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	1	68	theme	antibodies	139:148	arg1	source					254:259	the source	250:259	the source of red meat allergy	250:279	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	20	69	theme	future	1840:1845	arg1	research					1847:1854	future research	1840:1854	future research	1840:1854	Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
31156631	9	70	theme	acini	995:999	arg1	vesicles					970:977	the salivary secretory vesicles	947:977	the salivary secretory vesicles of the salivary acini	947:999	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	19	71	theme	certain	1609:1615	arg1	species					1622:1628	certain tick species	1609:1628	certain tick species	1609:1628	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	2	72	theme	Amblyomma	421:429	arg1	tick					415:418	the Gulf-Coast tick	400:418	the Gulf-Coast tick (Amblyomma maculatum)	400:440	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	72	theme	Amblyomma	421:429	arg1	maculatum					431:439	Amblyomma maculatum	421:439	Amblyomma maculatum	421:439	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	73	theme	approach	579:586	arg1	combination					548:558	a combination	546:558	a combination of immunoproteomic approach and, carbohydrate analysis	546:613	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	0	74	theme	Meat	97:100	arg1	Allergy					102:108	Red Meat Allergy	93:108	Red Meat Allergy	93:108	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
31156631	2	75	theme	dog	456:458	arg1	variabilis					478:487	Dermacentor variabilis	466:487	Dermacentor variabilis	466:487	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	75	theme	dog	456:458	arg1	tick					460:463	the American dog tick	443:463	the American dog tick (Dermacentor variabilis)	443:488	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	9	76	theme	secretory	1020:1028	arg1	nature					1030:1035	the secretory nature	1016:1035	the secretory nature of α-gal-containing antigens in ticks	1016:1073	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	2	77	theme	analysis	606:613	arg1	combination					548:558	a combination	546:558	a combination of immunoproteomic approach and, carbohydrate analysis	546:613	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	8	78	theme	F	802:802	arg1	treatment					804:812	PNGase F treatment	795:812	PNGase F treatment	795:812	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	9	79	theme	antigens	1057:1064	arg1	nature					1030:1035	the secretory nature	1016:1035	the secretory nature of α-gal-containing antigens in ticks	1016:1073	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	0	80	theme	Antigens	34:41	arg1	Discovery					0:8	Discovery	0:8	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species	0:72	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
31156631	1	81	theme	red	264:266	arg1	allergy					273:279	red meat allergy	264:279	red meat allergy	264:279	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	2	82	theme	Amblyomma	377:385	arg1	tick					371:374	the lone-star tick	357:374	the lone-star tick (Amblyomma americanum)	357:397	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	2	82	theme	Amblyomma	377:385	arg1	americanum					387:396	Amblyomma americanum	377:396	Amblyomma americanum	377:396	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31156631	14	83	from	α-gal	1284:1288	arg1	saliva					1299:1304	their saliva	1293:1304	their saliva	1293:1304	scapularis have α-gal in their saliva and salivary glands, but Am.
31156631	14	83	from	α-gal	1284:1288	arg1	glands					1319:1324	salivary glands	1310:1324	salivary glands	1310:1324	scapularis have α-gal in their saliva and salivary glands, but Am.
31156631	19	84	from	development	1669:1679	arg1	humans					1737:1742	humans	1737:1742	humans	1737:1742	Together, these data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans.
31156631	1	85	theme	allergy	273:279	arg1	Development					111:121	Development	111:121	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites	111:227	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	1	85	theme	allergy	273:279	arg1	source					254:259	the source	250:259	the source of red meat allergy	250:279	Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy.
31156631	11	86	theme	americanum	1080:1089	arg1	ticks					1091:1095	americanum ticks	1080:1095	americanum ticks	1080:1095	americanum ticks were fed on human blood (lacks α-gal) using a silicone membrane system to determine the source of the α-gal.
31156631	12	87	theme	glycan	1215:1220	arg1	analysis					1222:1229	N-linked glycan analysis	1206:1229	N-linked glycan analysis	1206:1229	N-linked glycan analysis revealed that Am.
31156631	0	88	theme	Tick	61:64	arg1	Species					66:72	North American Tick Species	46:72	North American Tick Species	46:72	Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy.
31156631	8	89	theme	N-linked	847:854	arg1	proteins					873:880	N-linked α-gal-containing proteins	847:880	N-linked α-gal-containing proteins	847:880	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	16	90	with	Consistent	1378:1387	arg1	analysis					1405:1412	the glycan analysis	1394:1412	the glycan analysis	1394:1412	Consistent with the glycan analysis, salivary samples from Am.
31156631	16	90	with	Consistent	1378:1387	arg1	samples					1424:1430	salivary samples	1415:1430	salivary samples from Am	1415:1438	Consistent with the glycan analysis, salivary samples from Am.
31156631	8	91	theme	proteins	873:880	arg1	deglycosylation					828:842	the deglycosylation	824:842	the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands	824:904	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	14	92	from	glands	1319:1324	arg1	α-gal					1284:1288	α-gal	1284:1288	α-gal	1284:1288	scapularis have α-gal in their saliva and salivary glands, but Am.
31156631	8	93	theme	tick	885:888	arg1	glands					899:904	tick salivary glands	885:904	tick salivary glands	885:904	PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands.
31156631	9	94	from	nature	1030:1035	arg1	ticks					1069:1073	ticks	1069:1073	ticks	1069:1073	Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.
31156631	2	95	theme	α-gal	329:333	arg1	presence					317:324	the presence	313:324	the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis)	313:535	In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis.
31256377	8	0	theme	quantitative	1192:1203	arg1	analysis					1205:1212	quantitative analysis	1192:1212	quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC)	1192:1287	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	7	1	from	loci	1122:1125	arg1	extent					1072:1077	extent	1072:1077	extent	1072:1077	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	7	1	from	loci	1122:1125	arg1	type					1063:1066	type	1063:1066	type	1063:1066	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	5	2	theme	I	637:637	arg1	collagen					639:646	mature type I collagen	625:646	mature type I collagen	625:646	These are the only two O-linked glycosides found in mature type I collagen.
31256377	4	3	attach	attached	442:449	arg2	unit					430:433	a single galactose unit	411:433	a single galactose unit	411:433	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	4	3	attach	attached	442:449	arg1	Hyl					406:408	Hyl	406:408	Hyl	406:408	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	4	3	attach	attached	442:449	arg1	group					397:401	the 5-hydroxyl group	382:401	the 5-hydroxyl group of Hyl	382:408	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	6	4	theme	collagen-cell	865:877	arg1	interaction					879:889	collagen-cell interaction	865:889	collagen-cell interaction	865:889	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	5	5	theme	O-linked	596:603	arg1	These					573:577	These	573:577	These	573:577	These are the only two O-linked glycosides found in mature type I collagen.
31256377	5	5	theme	O-linked	596:603	arg1	glycosides					605:614	the only two O-linked glycosides	583:614	the only two O-linked glycosides found in mature type I collagen	583:646	These are the only two O-linked glycosides found in mature type I collagen.
31256377	6	6	theme	processes	756:764	arg1	number					718:723	a number	716:723	a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction	716:889	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	6	7	theme	likely	766:771	arg1	processes					756:764	biological and pathological processes	728:764	biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction	728:889	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	6	8	theme	pathological	743:754	arg1	processes					756:764	biological and pathological processes	728:764	biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction	728:889	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	1	9	theme	I	49:49	arg1	collagen					51:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	1	9	theme	I	49:49	arg1	protein					92:98	the most abundant structural protein	63:98	the most abundant structural protein in most tissues and organs	63:125	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	7	10	theme	analytical	950:959	arg1	chemistry					961:969	analytical chemistry	950:969	analytical chemistry	950:969	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	7	11	theme	glycosylation	1082:1094	arg1	extent					1072:1077	extent	1072:1077	extent	1072:1077	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	7	11	theme	glycosylation	1082:1094	arg1	type					1063:1066	type	1063:1066	type	1063:1066	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	4	12	theme	5-hydroxyl	386:395	arg1	Hyl					406:408	Hyl	406:408	Hyl	406:408	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	4	12	theme	5-hydroxyl	386:395	arg1	group					397:401	the 5-hydroxyl group	382:401	the 5-hydroxyl group of Hyl	382:408	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	6	13	theme	biological	728:737	arg1	processes					756:764	biological and pathological processes	728:764	biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction	728:889	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	2	14	theme	residues	263:270	arg1	modifications					233:245	sequential posttranslational modifications	204:245	sequential posttranslational modifications of lysine (Lys) residues	204:270	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	6	15	theme	intermolecular	831:844	arg1	cross-linking					846:858	intermolecular cross-linking	831:858	intermolecular cross-linking	831:858	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	8	16	theme	mass	1349:1352	arg1	spectrometry					1354:1365	HPLC-tandem mass spectrometry	1337:1365	HPLC-tandem mass spectrometry	1337:1365	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	8	17	theme	glycosylation	1226:1238	arg1	analysis					1205:1212	quantitative analysis	1192:1212	quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC)	1192:1287	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	8	17	theme	glycosylation	1226:1238	arg1	analysis					1325:1332	semiquantitative, site-specific analysis	1293:1332	semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry	1293:1365	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	6	18	from	roles	796:800	arg1	cross-linking					846:858	intermolecular cross-linking	831:858	intermolecular cross-linking	831:858	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	6	18	from	roles	796:800	arg1	interaction					879:889	collagen-cell interaction	865:889	collagen-cell interaction	865:889	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	6	18	from	roles	796:800	arg1	fibrillogenesis					814:828	collagen fibrillogenesis	805:828	collagen fibrillogenesis	805:828	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	4	19	theme	Hyl	406:408	arg1	Hyl					406:408	Hyl	406:408	Hyl	406:408	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	4	19	theme	Hyl	406:408	arg1	group					397:401	the 5-hydroxyl group	382:401	the 5-hydroxyl group of Hyl	382:408	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	1	20	theme	abundant	72:79	arg1	collagen					51:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	1	20	theme	abundant	72:79	arg1	protein					92:98	the most abundant structural protein	63:98	the most abundant structural protein in most tissues and organs	63:125	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	8	21	theme	collagen	1217:1224	arg1	glycosylation					1226:1238	collagen glycosylation	1217:1238	collagen glycosylation	1217:1238	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	0	22	theme	I	22:22	arg1	Collagen					24:31	Type I Collagen	17:31	Type I Collagen	17:31	Glycosylation of Type I Collagen.
31256377	2	23	theme	lysine	250:255	arg1	residues					263:270	lysine (Lys) residues	250:270	lysine (Lys) residues	250:270	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	1	24	theme	structural	81:90	arg1	collagen					51:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	1	24	theme	structural	81:90	arg1	protein					92:98	the most abundant structural protein	63:98	the most abundant structural protein in most tissues and organs	63:125	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	7	25	theme	molecular/cell	923:936	arg1	biology					938:944	molecular/cell biology	923:944	molecular/cell biology	923:944	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	8	26	theme	high-performance	1243:1258	arg1	HPLC					1283:1286	HPLC	1283:1286	HPLC	1283:1286	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	8	26	theme	high-performance	1243:1258	arg1	chromatography					1267:1280	high-performance liquid chromatography	1243:1280	high-performance liquid chromatography (HPLC)	1243:1287	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	0	27	theme	Type	17:20	arg1	Collagen					24:31	Type I Collagen	17:31	Type I Collagen	17:31	Glycosylation of Type I Collagen.
31256377	6	28	theme	regulatory	785:794	arg1	roles					796:800	its regulatory roles	781:800	its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction	781:889	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	4	29	theme	single	413:418	arg1	unit					430:433	a single galactose unit	411:433	a single galactose unit	411:433	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	7	30	theme	glycosylation	1009:1021	arg1	mechanisms					986:995	the molecular mechanisms	972:995	the molecular mechanisms of collagen glycosylation	972:1021	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	6	31	theme	collagen	805:812	arg1	fibrillogenesis					814:828	collagen fibrillogenesis	805:828	collagen fibrillogenesis	805:828	It has been shown that this modification is critically involved in a number of biological and pathological processes likely through its regulatory roles in collagen fibrillogenesis, intermolecular cross-linking, and collagen-cell interaction.
31256377	0	32	gly	Glycosylation	0:12	arg1	Collagen					24:31	Type I Collagen	17:31	Type I Collagen	17:31	Glycosylation of Type I Collagen.
31256377	0	33	theme	Collagen	24:31	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation of Type I Collagen	0:31	Glycosylation of Type I Collagen.
31256377	7	34	dep	type	1063:1066	arg1	the					1059:1061	the	1059:1061	the	1059:1061	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	2	35	theme	unique	139:144	arg1	characteristics					173:187	the unique and functionally important characteristics	135:187	the unique and functionally important characteristics of collagen	135:199	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	2	36	theme	posttranslational	215:231	arg1	modifications					233:245	sequential posttranslational modifications	204:245	sequential posttranslational modifications of lysine (Lys) residues	204:270	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	5	37	link	O-linked	596:603	arg1	These					573:577	These	573:577	These	573:577	These are the only two O-linked glycosides found in mature type I collagen.
31256377	5	37	link	O-linked	596:603	arg1	glycosides					605:614	the only two O-linked glycosides	583:614	the only two O-linked glycosides found in mature type I collagen	583:646	These are the only two O-linked glycosides found in mature type I collagen.
31256377	7	38	theme	specific	1103:1110	arg1	loci					1122:1125	the specific molecular loci	1099:1125	the specific molecular loci	1099:1125	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	4	39	theme	galactose	420:428	arg1	unit					430:433	a single galactose unit	411:433	a single galactose unit	411:433	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	2	40	theme	sequential	204:213	arg1	modifications					233:245	sequential posttranslational modifications	204:245	sequential posttranslational modifications of lysine (Lys) residues	204:270	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	7	41	theme	collagen	1000:1007	arg1	glycosylation					1009:1021	collagen glycosylation	1000:1021	collagen glycosylation	1000:1021	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	7	42	theme	molecular	1112:1120	arg1	loci					1122:1125	the specific molecular loci	1099:1125	the specific molecular loci	1099:1125	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	5	43	theme	mature	625:630	arg1	collagen					639:646	mature type I collagen	625:646	mature type I collagen	625:646	These are the only two O-linked glycosides found in mature type I collagen.
31256377	2	44	theme	collagen	192:199	arg1	characteristics					173:187	the unique and functionally important characteristics	135:187	the unique and functionally important characteristics of collagen	135:199	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	8	45	dep	semiquantitative	1293:1308	arg1	site-specific					1311:1323	site-specific	1311:1323	site-specific	1311:1323	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	1	46	theme	most	103:106	arg1	tissues					108:114	tissues	108:114	tissues	108:114	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	4	47	theme	further	488:494	arg1	glucose					496:502	further glucose	488:502	further glucose	488:502	Then, to the 5-hydroxyl group of Hyl, a single galactose unit can be attached to form galactosyl-Hyl (Gal-Hyl) and further glucose can be added to Gal-Hyl to form glucosylgalactosyl-Hyl (GlcGal-Hyl).
31256377	5	48	theme	type	632:635	arg1	collagen					639:646	mature type I collagen	625:646	mature type I collagen	625:646	These are the only two O-linked glycosides found in mature type I collagen.
31256377	7	49	theme	molecular	976:984	arg1	mechanisms					986:995	the molecular mechanisms	972:995	the molecular mechanisms of collagen glycosylation	972:1021	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	1	50	from	protein	92:98	arg1	tissues					108:114	tissues	108:114	tissues	108:114	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	1	50	from	protein	92:98	arg1	organs					120:125	organs	120:125	organs	120:125	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	8	51	theme	liquid	1260:1265	arg1	HPLC					1283:1286	HPLC	1283:1286	HPLC	1283:1286	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	8	51	theme	liquid	1260:1265	arg1	chromatography					1267:1280	high-performance liquid chromatography	1243:1280	high-performance liquid chromatography (HPLC)	1243:1287	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	3	52	theme	endoplasmic	280:290	arg1	reticulum					292:300	the endoplasmic reticulum	276:300	the endoplasmic reticulum	276:300	In the endoplasmic reticulum, hydroxylation of specific Lys occurs producing 5-hydroxylysine (Hyl).
31256377	2	53	theme	characteristics	173:187	arg1	characteristics					173:187	the unique and functionally important characteristics	135:187	the unique and functionally important characteristics of collagen	135:199	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	2	53	theme	characteristics	173:187	arg1	One					128:130	One	128:130	One	128:130	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	8	54	theme	HPLC-tandem	1337:1347	arg1	spectrometry					1354:1365	HPLC-tandem mass spectrometry	1337:1365	HPLC-tandem mass spectrometry	1337:1365	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31256377	5	55	located	found	616:620	arg2	These					573:577	These	573:577	These	573:577	These are the only two O-linked glycosides found in mature type I collagen.
31256377	5	55	located	found	616:620	arg2	glycosides					605:614	the only two O-linked glycosides	583:614	the only two O-linked glycosides found in mature type I collagen	583:646	These are the only two O-linked glycosides found in mature type I collagen.
31256377	5	55	located	found	616:620	arg1	collagen					639:646	mature type I collagen	625:646	mature type I collagen	625:646	These are the only two O-linked glycosides found in mature type I collagen.
31256377	3	56	theme	specific	320:327	arg1	Lys					329:331	specific Lys	320:331	specific Lys	320:331	In the endoplasmic reticulum, hydroxylation of specific Lys occurs producing 5-hydroxylysine (Hyl).
31256377	2	57	theme	important	163:171	arg1	characteristics					173:187	the unique and functionally important characteristics	135:187	the unique and functionally important characteristics of collagen	135:199	One of the unique and functionally important characteristics of collagen is sequential posttranslational modifications of lysine (Lys) residues.
31256377	1	58	theme	Fibrillar	34:42	arg1	collagen					51:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	1	58	theme	Fibrillar	34:42	arg1	protein					92:98	the most abundant structural protein	63:98	the most abundant structural protein in most tissues and organs	63:125	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	7	59	from	advances	911:918	arg1	chemistry					961:969	analytical chemistry	950:969	analytical chemistry	950:969	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	7	59	from	advances	911:918	arg1	biology					938:944	molecular/cell biology	923:944	molecular/cell biology	923:944	Recently, with the advances in molecular/cell biology and analytical chemistry, the molecular mechanisms of collagen glycosylation have been gradually deciphered, and the type and extent of glycosylation at the specific molecular loci can now be quantitatively analyzed.
31256377	3	60	theme	Lys	329:331	arg1	hydroxylation					303:315	hydroxylation	303:315	hydroxylation of specific Lys	303:331	In the endoplasmic reticulum, hydroxylation of specific Lys occurs producing 5-hydroxylysine (Hyl).
31256377	1	61	theme	type	44:47	arg1	collagen					51:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen	34:58	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	1	61	theme	type	44:47	arg1	protein					92:98	the most abundant structural protein	63:98	the most abundant structural protein in most tissues and organs	63:125	Fibrillar type I collagen is the most abundant structural protein in most tissues and organs.
31256377	8	62	theme	semiquantitative	1293:1308	arg1	analysis					1325:1332	semiquantitative, site-specific analysis	1293:1332	semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry	1293:1365	In this chapter, we describe quantitative analysis of collagen glycosylation by high-performance liquid chromatography (HPLC) and semiquantitative, site-specific analysis by HPLC-tandem mass spectrometry.
31079966	3	0	theme	M1	818:819	arg1	formation					834:842	core M1 disaccharide formation	813:842	core M1 disaccharide formation	813:842	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	4	1	theme	M1	987:988	arg1	hindrance					969:977	steric hindrance	962:977	steric hindrance of core M1	962:988	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	1	theme	M1	987:988	arg1	form					1015:1018	the sole 1,2-O-modified form	991:1018	the sole 1,2-O-modified form among protein binding sugar residue found in mammals	991:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	1	2	theme	functional	184:193	arg1	effects					195:201	Structural and functional effects	169:201	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	169:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	4	3	theme	acid	908:911	arg1	signals					863:869	No long-range NOE signals	845:869	No long-range NOE signals of glycan-amino acid nor inter amino acid	845:911	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	3	4	contain	having	691:696	arg1	glycopeptide					678:689	synthetic glycopeptide	668:689	synthetic glycopeptide having different length of the O-mannosylated glycans	668:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	3	4	contain	having	691:696	arg2	length					708:713	different length	698:713	different length of the O-mannosylated glycans	698:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	0	5	theme	O-mannosylated	85:98	arg1	position					100:107	O-mannosylated position	85:107	O-mannosylated position of α-dystroglycan	85:125	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	4	6	theme	core	982:985	arg1	M1					987:988	core M1	982:988	core M1	982:988	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	7	theme	amino	902:906	arg1	acid					908:911	inter amino acid	896:911	inter amino acid	896:911	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	0	8	theme	α-dystroglycan	112:125	arg1	position					100:107	O-mannosylated position	85:107	O-mannosylated position of α-dystroglycan	85:125	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	1	9	theme	α-dystroglycan	392:405	arg1	372TRGAIIQTPTLGPIQPTRV390					417:441	372TRGAIIQTPTLGPIQPTRV390	417:441	372TRGAIIQTPTLGPIQPTRV390	417:441	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	1	9	theme	α-dystroglycan	392:405	arg1	fragment					407:414	an α-dystroglycan fragment	389:414	an α-dystroglycan fragment	389:414	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	4	10	theme	acid	887:890	arg1	signals					863:869	No long-range NOE signals	845:869	No long-range NOE signals of glycan-amino acid nor inter amino acid	845:911	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	1	11	theme	fragment	407:414	arg1	library					378:384	a core M1 glycoform focused library	350:384	a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390	350:441	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	4	12	theme	glycan-amino	874:885	arg1	acid					887:890	glycan-amino acid	874:890	glycan-amino acid	874:890	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	3	13	theme	comparative	640:650	arg1	analysis					656:663	The comparative NMR analysis	636:663	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans	636:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	0	14	theme	POMGnT1	130:136	arg1	modification					155:166	POMGnT1 catalyzed GlcNAc modification	130:166	POMGnT1 catalyzed GlcNAc modification	130:166	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	4	15	theme	steric	962:967	arg1	hindrance					969:977	steric hindrance	962:977	steric hindrance of core M1	962:988	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	15	theme	steric	962:967	arg1	form					1015:1018	the sole 1,2-O-modified form	991:1018	the sole 1,2-O-modified form among protein binding sugar residue found in mammals	991:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	0	16	gly	O-mannosylated	85:98	arg1	position					100:107	O-mannosylated position	85:107	O-mannosylated position of α-dystroglycan	85:125	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	2	17	theme	fluorescence-assisted	461:481	arg1	system					494:499	Evanescent-field fluorescence-assisted microarray system	444:499	Evanescent-field fluorescence-assisted microarray system	444:499	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	4	18	theme	sugar	1042:1046	arg1	residue					1048:1054	protein binding sugar residue	1026:1054	protein binding sugar residue found in mammals	1026:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	2	19	theme	M1	610:611	arg1	glycan					613:618	core M1 glycan	605:618	core M1 glycan of the library	605:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	3	20	theme	disaccharide	821:832	arg1	formation					834:842	core M1 disaccharide formation	813:842	core M1 disaccharide formation	813:842	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	2	21	theme	plant	545:549	arg1	lectins					551:557	plant lectins	545:557	plant lectins	545:557	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	1	22	theme	core	206:209	arg1	glycan					219:224	core M1 type glycan	206:224	core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	206:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	2	23	theme	lectins	551:557	arg1	pattern					534:540	the specific binding pattern	513:540	the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library	513:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	2	24	theme	glycan	585:590	arg1	structure					592:600	the glycan structure	581:600	the glycan structure of core M1 glycan of the library	581:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	4	25	theme	NOE	859:861	arg1	signals					863:869	No long-range NOE signals	845:869	No long-range NOE signals of glycan-amino acid nor inter amino acid	845:911	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	26	theme	sole	995:998	arg1	form					1015:1018	the sole 1,2-O-modified form	991:1018	the sole 1,2-O-modified form among protein binding sugar residue found in mammals	991:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	26	theme	sole	995:998	arg1	hindrance					969:977	steric hindrance	962:977	steric hindrance of core M1	962:988	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	1	27	theme	M1	211:212	arg1	glycan					219:224	core M1 type glycan	206:224	core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	206:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	0	28	theme	Synthetic	0:8	arg1	glycopeptides					10:22	Synthetic glycopeptides	0:22	Synthetic glycopeptides	0:22	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	3	29	theme	synthetic	668:676	arg1	glycopeptide					678:689	synthetic glycopeptide	668:689	synthetic glycopeptide having different length of the O-mannosylated glycans	668:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	1	30	theme	type	214:217	arg1	glycan					219:224	core M1 type glycan	206:224	core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	206:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	0	31	theme	specific	31:38	arg1	pattern					48:54	specific binding pattern	31:54	specific binding pattern	31:54	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	0	32	theme	GlcNAc	148:153	arg1	modification					155:166	POMGnT1 catalyzed GlcNAc modification	130:166	POMGnT1 catalyzed GlcNAc modification	130:166	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	1	33	link	O-linked	260:267	arg1	β1,2-N-acetylglucosaminyltransferase					277:312	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1	252:314	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	252:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	1	33	link	O-linked	260:267	arg1	POMGnT1					317:323	POMGnT1	317:323	POMGnT1	317:323	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	3	34	theme	NMR	652:654	arg1	analysis					656:663	The comparative NMR analysis	636:663	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans	636:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	1	35	theme	glycan	219:224	arg1	effects					195:201	Structural and functional effects	169:201	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	169:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	4	36	theme	long-range	848:857	arg1	signals					863:869	No long-range NOE signals	845:869	No long-range NOE signals of glycan-amino acid nor inter amino acid	845:911	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	0	37	theme	catalyzed	138:146	arg1	modification					155:166	POMGnT1 catalyzed GlcNAc modification	130:166	POMGnT1 catalyzed GlcNAc modification	130:166	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	3	38	theme	conformational	756:769	arg1	change					771:776	a conformational change	754:776	a conformational change of the peptide backbone	754:800	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	2	39	theme	specific	517:524	arg1	pattern					534:540	the specific binding pattern	513:540	the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library	513:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	3	40	theme	different	698:706	arg1	length					708:713	different length	698:713	different length of the O-mannosylated glycans	698:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	2	41	theme	Evanescent-field	444:459	arg1	system					494:499	Evanescent-field fluorescence-assisted microarray system	444:499	Evanescent-field fluorescence-assisted microarray system	444:499	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	0	42	theme	binding	40:46	arg1	pattern					48:54	specific binding pattern	31:54	specific binding pattern	31:54	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	1	43	theme	core	352:355	arg1	library					378:384	a core M1 glycoform focused library	350:384	a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390	350:441	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	2	44	theme	glycan	613:618	arg1	structure					592:600	the glycan structure	581:600	the glycan structure of core M1 glycan of the library	581:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	0	45	gly	glycopeptides	10:22	arg2	glycopeptides					10:22	Synthetic glycopeptides	0:22	Synthetic glycopeptides	0:22	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	3	46	gly	glycopeptide	678:689	arg2	glycopeptide					678:689	synthetic glycopeptide	668:689	synthetic glycopeptide having different length of the O-mannosylated glycans	668:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	0	47	theme	conformational	60:73	arg1	change					75:80	conformational change	60:80	conformational change	60:80	Synthetic glycopeptides reveal specific binding pattern and conformational change at O-mannosylated position of α-dystroglycan by POMGnT1 catalyzed GlcNAc modification.
31079966	1	48	theme	M1	357:358	arg1	library					378:384	a core M1 glycoform focused library	350:384	a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390	350:441	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	4	49	theme	1,2-O-modified	1000:1013	arg1	form					1015:1018	the sole 1,2-O-modified form	991:1018	the sole 1,2-O-modified form among protein binding sugar residue found in mammals	991:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	49	theme	1,2-O-modified	1000:1013	arg1	hindrance					969:977	steric hindrance	962:977	steric hindrance of core M1	962:988	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	3	50	theme	glycopeptide	678:689	arg1	analysis					656:663	The comparative NMR analysis	636:663	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans	636:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	2	51	theme	library	627:633	arg1	glycan					613:618	core M1 glycan	605:618	core M1 glycan of the library	605:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	1	52	theme	glycoform	360:368	arg1	library					378:384	a core M1 glycoform focused library	350:384	a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390	350:441	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	4	53	theme	binding	1034:1040	arg1	residue					1048:1054	protein binding sugar residue	1026:1054	protein binding sugar residue found in mammals	1026:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	3	54	theme	peptide	785:791	arg1	backbone					793:800	the peptide backbone	781:800	the peptide backbone	781:800	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	1	55	theme	focused	370:376	arg1	library					378:384	a core M1 glycoform focused library	350:384	a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390	350:441	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	3	56	theme	backbone	793:800	arg1	change					771:776	a conformational change	754:776	a conformational change of the peptide backbone	754:800	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	3	57	theme	O-mannosylated	722:735	arg1	glycans					737:743	the O-mannosylated glycans	718:743	the O-mannosylated glycans	718:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	4	58	theme	conformational	926:939	arg1	change					941:946	the conformational change	922:946	the conformational change	922:946	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	1	59	theme	protein	252:258	arg1	β1,2-N-acetylglucosaminyltransferase					277:312	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1	252:314	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	252:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	1	59	theme	protein	252:258	arg1	POMGnT1					317:323	POMGnT1	317:323	POMGnT1	317:323	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	4	60	theme	inter	896:900	arg1	acid					908:911	inter amino acid	896:911	inter amino acid	896:911	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	3	61	theme	glycans	737:743	arg1	length					708:713	different length	698:713	different length of the O-mannosylated glycans	698:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	4	62	located	found	1056:1060	arg1	mammals					1065:1071	mammals	1065:1071	mammals	1065:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	62	located	found	1056:1060	arg2	residue					1048:1054	protein binding sugar residue	1026:1054	protein binding sugar residue found in mammals	1026:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	4	63	theme	protein	1026:1032	arg1	residue					1048:1054	protein binding sugar residue	1026:1054	protein binding sugar residue found in mammals	1026:1071	No long-range NOE signals of glycan-amino acid nor inter amino acid indicate the conformational change is induced by steric hindrance of core M1, the sole 1,2-O-modified form among protein binding sugar residue found in mammals.
31079966	1	64	theme	O-linked	260:267	arg1	β1,2-N-acetylglucosaminyltransferase					277:312	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1	252:314	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	252:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	1	64	theme	O-linked	260:267	arg1	POMGnT1					317:323	POMGnT1	317:323	POMGnT1	317:323	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	2	65	theme	core	605:608	arg1	glycan					613:618	core M1 glycan	605:618	core M1 glycan of the library	605:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	1	66	dep	glycan	219:224	arg1	modification					226:237	modification	226:237	core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	206:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	2	67	theme	binding	526:532	arg1	pattern					534:540	the specific binding pattern	513:540	the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library	513:633	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	1	68	theme	Structural	169:178	arg1	effects					195:201	Structural and functional effects	169:201	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	169:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	2	69	theme	microarray	483:492	arg1	system					494:499	Evanescent-field fluorescence-assisted microarray system	444:499	Evanescent-field fluorescence-assisted microarray system	444:499	Evanescent-field fluorescence-assisted microarray system illuminated the specific binding pattern of plant lectins that can discriminate the glycan structure of core M1 glycan of the library.
31079966	1	70	theme	mannose	269:275	arg1	β1,2-N-acetylglucosaminyltransferase					277:312	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1	252:314	protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1)	252:324	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	1	70	theme	mannose	269:275	arg1	POMGnT1					317:323	POMGnT1	317:323	POMGnT1	317:323	Structural and functional effects of core M1 type glycan modification catalyzed by protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) were investigated using a core M1 glycoform focused library of an α-dystroglycan fragment, 372TRGAIIQTPTLGPIQPTRV390.
31079966	3	71	theme	core	813:816	arg1	formation					834:842	core M1 disaccharide formation	813:842	core M1 disaccharide formation	813:842	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
31079966	3	72	gly	O-mannosylated	722:735	arg1	glycans					737:743	the O-mannosylated glycans	718:743	the O-mannosylated glycans	718:743	The comparative NMR analysis of synthetic glycopeptide having different length of the O-mannosylated glycans revealed a conformational change of the peptide backbone along with core M1 disaccharide formation.
30962710	0	0	theme	renal	87:91	arg1	carcinoma					98:106	renal cell carcinoma	87:106	renal cell carcinoma	87:106	Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma.
30962710	2	1	theme	renal	351:355	arg1	RCC					373:375	RCC	373:375	RCC	373:375	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	2	1	theme	renal	351:355	arg1	carcinoma					362:370	human renal cell carcinoma	345:370	human renal cell carcinoma (RCC)	345:376	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	5	2	theme	OGT	749:751	arg1	knockdown					753:761	OGT knockdown	749:761	OGT knockdown	749:761	A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells.
30962710	3	3	from	levels	403:408	arg1	tissues					499:505	10 paired clinical tissues	480:505	10 paired clinical tissues	480:505	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	3	3	from	levels	403:408	arg1	lines					470:474	human RCC cell lines	455:474	human RCC cell lines	455:474	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	8	4	theme	O-GlcNAcylation	1004:1018	arg1	levels					1020:1025	RESULTS O-GlcNAcylation levels	996:1025	RESULTS O-GlcNAcylation levels	996:1025	RESULTS O-GlcNAcylation levels and OGT expression were increased in RCC, and the high amounts correlated with poor patient prognosis.
30962710	9	5	theme	RCC	1169:1171	arg1	proliferation					1178:1190	RCC cell proliferation	1169:1190	RCC cell proliferation	1169:1190	OGT knockdown significantly suppressed RCC cell proliferation in vitro and in vivo.
30962710	2	6	theme	human	345:349	arg1	RCC					373:375	RCC	373:375	RCC	373:375	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	2	6	theme	human	345:349	arg1	carcinoma					362:370	human renal cell carcinoma	345:370	human renal cell carcinoma (RCC)	345:376	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	11	7	theme	RCC	1473:1475	arg1	therapy					1477:1483	RCC therapy	1473:1483	RCC therapy in the future	1473:1497	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	11	8	from	roles	1363:1367	arg1	development					1403:1413	the development	1399:1413	the development of RCC	1399:1420	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	8	9	theme	OGT	1031:1033	arg1	expression					1035:1044	OGT expression	1031:1044	OGT expression	1031:1044	RESULTS O-GlcNAcylation levels and OGT expression were increased in RCC, and the high amounts correlated with poor patient prognosis.
30962710	9	10	theme	cell	1173:1176	arg1	proliferation					1178:1190	RCC cell proliferation	1169:1190	RCC cell proliferation	1169:1190	OGT knockdown significantly suppressed RCC cell proliferation in vitro and in vivo.
30962710	3	11	theme	Western	524:530	arg1	blot					532:535	Western blot	524:535	Western blot	524:535	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	7	12	theme	Co-immunoprecipitation	848:869	arg1	assays					871:876	Co-immunoprecipitation assays	848:876	Co-immunoprecipitation assays	848:876	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	1	13	theme	various	262:268	arg1	cancers					270:276	various cancers	262:276	various cancers	262:276	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	0	14	theme	cell	93:96	arg1	carcinoma					98:106	renal cell carcinoma	87:106	renal cell carcinoma	87:106	Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma.
30962710	11	15	from	therapy	1477:1483	arg1	future					1492:1497	future	1492:1497	future	1492:1497	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	6	16	theme	Cell	777:780	arg1	apoptosis					782:790	Cell apoptosis	777:790	Cell apoptosis	777:790	Cell apoptosis and cell cycle assays were performed by flow cytometry.
30962710	3	17	theme	paired	483:488	arg1	tissues					499:505	10 paired clinical tissues	480:505	10 paired clinical tissues	480:505	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	1	18	theme	cancers	270:276	arg1	progression					247:257	the progression	243:257	the progression of various cancers	243:276	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	3	19	theme	O-GlcNAc-transferase	414:433	arg1	expression					441:450	O-GlcNAc-transferase (OGT) expression	414:450	O-GlcNAc-transferase (OGT) expression	414:450	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	5	20	theme	in	730:731	arg1	effects					738:744	the in vivo effects	726:744	the in vivo effects of OGT knockdown in RCC cells	726:774	A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells.
30962710	11	21	dep	CONCLUSION	1295:1304	arg1	provide					1321:1327	provide	1321:1327	provide	1321:1327	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	11	22	theme	oncogenic	1353:1361	arg1	roles					1363:1367	the oncogenic roles	1349:1367	the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC	1349:1420	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	7	23	theme	receptor	922:929	arg1	O-GlcNAcylation					938:952	epidermal growth factor receptor (EGFR) O-GlcNAcylation	898:952	epidermal growth factor receptor (EGFR) O-GlcNAcylation	898:952	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	4	24	from	effects	574:580	arg1	proliferation					613:625	RCC cell proliferation	604:625	RCC cell proliferation in vitro	604:634	Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay.
30962710	11	25	theme	RCC	1418:1420	arg1	development					1403:1413	the development	1399:1413	the development of RCC	1399:1420	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	0	26	theme	OGT	11:13	arg1	expression					15:24	Suppressed OGT expression	0:24	Suppressed OGT expression	0:24	Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma.
30962710	11	27	theme	O-GlcNAcylation	1372:1386	arg1	roles					1363:1367	the oncogenic roles	1349:1367	the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC	1349:1420	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	8	28	theme	high	1077:1080	arg1	amounts					1082:1088	the high amounts	1073:1088	the high amounts	1073:1088	RESULTS O-GlcNAcylation levels and OGT expression were increased in RCC, and the high amounts correlated with poor patient prognosis.
30962710	1	29	theme	post-translational	182:199	arg1	-acetylglucosamine					128:145	PURPOSE O-linked N -acetylglucosamine	109:145	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation)	109:175	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	1	29	theme	post-translational	182:199	arg1	modification					201:212	a post-translational modification	180:212	a post-translational modification	180:212	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	0	30	theme	Suppressed	0:9	arg1	expression					15:24	Suppressed OGT expression	0:24	Suppressed OGT expression	0:24	Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma.
30962710	6	31	theme	cell	796:799	arg1	assays					807:812	cell cycle assays	796:812	cell cycle assays	796:812	Cell apoptosis and cell cycle assays were performed by flow cytometry.
30962710	7	32	theme	growth	908:913	arg1	receptor					922:929	epidermal growth factor receptor	898:929	epidermal growth factor receptor (EGFR) O-GlcNAcylation	898:952	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	7	32	theme	growth	908:913	arg1	EGFR					932:935	EGFR	932:935	EGFR	932:935	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	2	33	theme	study	306:310	arg1	purpose					283:289	The purpose	279:289	The purpose of the present study	279:310	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	4	34	theme	Cell	657:660	arg1	assay					677:681	Cell Counting Kit-8 assay	657:681	Cell Counting Kit-8 assay	657:681	Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay.
30962710	8	35	theme	RESULTS	996:1002	arg1	levels					1020:1025	RESULTS O-GlcNAcylation levels	996:1025	RESULTS O-GlcNAcylation levels	996:1025	RESULTS O-GlcNAcylation levels and OGT expression were increased in RCC, and the high amounts correlated with poor patient prognosis.
30962710	5	36	theme	xenograft	686:694	arg1	assay					696:700	A xenograft assay	684:700	A xenograft assay	684:700	A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells.
30962710	7	37	theme	factor	915:920	arg1	receptor					922:929	epidermal growth factor receptor	898:929	epidermal growth factor receptor (EGFR) O-GlcNAcylation	898:952	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	7	37	theme	factor	915:920	arg1	EGFR					932:935	EGFR	932:935	EGFR	932:935	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	2	38	theme	present	298:304	arg1	study					306:310	the present study	294:310	the present study	294:310	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	3	39	theme	human	455:459	arg1	lines					470:474	human RCC cell lines	455:474	human RCC cell lines	455:474	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	1	40	theme	PURPOSE	109:115	arg1	-acetylglucosamine					128:145	PURPOSE O-linked N -acetylglucosamine	109:145	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation)	109:175	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	1	40	theme	PURPOSE	109:115	arg1	modification					201:212	a post-translational modification	180:212	a post-translational modification	180:212	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	3	41	theme	RCC	461:463	arg1	lines					470:474	human RCC cell lines	455:474	human RCC cell lines	455:474	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	5	42	theme	knockdown	753:761	arg1	effects					738:744	the in vivo effects	726:744	the in vivo effects of OGT knockdown in RCC cells	726:774	A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells.
30962710	4	43	theme	Counting	662:669	arg1	assay					677:681	Cell Counting Kit-8 assay	657:681	Cell Counting Kit-8 assay	657:681	Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay.
30962710	6	44	theme	flow	832:835	arg1	cytometry					837:845	flow cytometry	832:845	flow cytometry	832:845	Cell apoptosis and cell cycle assays were performed by flow cytometry.
30962710	11	45	theme	OGT	1392:1394	arg1	roles					1363:1367	the oncogenic roles	1349:1367	the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC	1349:1420	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	0	46	theme	cell	35:38	arg1	proliferation					40:52	cell proliferation	35:52	cell proliferation	35:52	Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma.
30962710	0	47	from	expression	73:82	arg1	carcinoma					98:106	renal cell carcinoma	87:106	renal cell carcinoma	87:106	Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma.
30962710	3	48	from	expression	441:450	arg1	tissues					499:505	10 paired clinical tissues	480:505	10 paired clinical tissues	480:505	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	3	48	from	expression	441:450	arg1	lines					470:474	human RCC cell lines	455:474	human RCC cell lines	455:474	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	3	49	theme	METHODS	379:385	arg1	levels					403:408	METHODS O-GlcNAcylation levels	379:408	METHODS O-GlcNAcylation levels	379:408	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	8	50	theme	poor	1106:1109	arg1	prognosis					1119:1127	poor patient prognosis	1106:1127	poor patient prognosis	1106:1127	RESULTS O-GlcNAcylation levels and OGT expression were increased in RCC, and the high amounts correlated with poor patient prognosis.
30962710	7	51	used	used	883:886	arg2	assays					871:876	Co-immunoprecipitation assays	848:876	Co-immunoprecipitation assays	848:876	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	1	52	theme	O-linked	117:124	arg1	-acetylglucosamine					128:145	PURPOSE O-linked N -acetylglucosamine	109:145	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation)	109:175	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	1	52	theme	O-linked	117:124	arg1	modification					201:212	a post-translational modification	180:212	a post-translational modification	180:212	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	3	53	theme	O-GlcNAcylation	387:401	arg1	levels					403:408	METHODS O-GlcNAcylation levels	379:408	METHODS O-GlcNAcylation levels	379:408	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	5	54	dep	in	730:731	arg1	vivo					733:736	vivo	733:736	vivo	733:736	A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells.
30962710	3	55	theme	clinical	490:497	arg1	tissues					499:505	10 paired clinical tissues	480:505	10 paired clinical tissues	480:505	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	1	56	theme	N	126:126	arg1	-acetylglucosamine					128:145	PURPOSE O-linked N -acetylglucosamine	109:145	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation)	109:175	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	1	56	theme	N	126:126	arg1	modification					201:212	a post-translational modification	180:212	a post-translational modification	180:212	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	1	57	link	O-linked	117:124	arg1	-acetylglucosamine					128:145	PURPOSE O-linked N -acetylglucosamine	109:145	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation)	109:175	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	1	57	link	O-linked	117:124	arg1	modification					201:212	a post-translational modification	180:212	a post-translational modification	180:212	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	5	58	theme	RCC	766:768	arg1	cells					770:774	RCC cells	766:774	RCC cells	766:774	A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells.
30962710	3	59	theme	cell	465:468	arg1	lines					470:474	human RCC cell lines	455:474	human RCC cell lines	455:474	METHODS O-GlcNAcylation levels and O-GlcNAc-transferase (OGT) expression in human RCC cell lines and 10 paired clinical tissues were detected by Western blot and Immunohistochemis-try.
30962710	7	60	theme	epidermal	898:906	arg1	receptor					922:929	epidermal growth factor receptor	898:929	epidermal growth factor receptor (EGFR) O-GlcNAcylation	898:952	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	7	60	theme	epidermal	898:906	arg1	EGFR					932:935	EGFR	932:935	EGFR	932:935	Co-immunoprecipitation assays were used to assess epidermal growth factor receptor (EGFR) O-GlcNAcylation and the interaction between OGT and EGFR.
30962710	1	61	theme	vital	229:233	arg1	role					235:238	a vital role	227:238	a vital role	227:238	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	11	62	theme	novel	1329:1333	arg1	insights					1335:1342	novel insights	1329:1342	novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC	1329:1420	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	6	63	theme	cycle	801:805	arg1	assays					807:812	cell cycle assays	796:812	cell cycle assays	796:812	Cell apoptosis and cell cycle assays were performed by flow cytometry.
30962710	1	64	dep	-acetylglucosamine	128:145	arg1	O-GlcNAcylation					160:174	O-GlcNAcylation	160:174	O-GlcNAcylation	160:174	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	1	64	dep	-acetylglucosamine	128:145	arg1	O-GlcNAc					148:155	O-GlcNAc	148:155	O-GlcNAc	148:155	PURPOSE O-linked N -acetylglucosamine (O-GlcNAc or O-GlcNAcylation) is a post-translational modification, which plays a vital role in the progression of various cancers.
30962710	9	65	theme	OGT	1130:1132	arg1	knockdown					1134:1142	OGT knockdown	1130:1142	OGT knockdown	1130:1142	OGT knockdown significantly suppressed RCC cell proliferation in vitro and in vivo.
30962710	4	66	theme	Kit-8	671:675	arg1	assay					677:681	Cell Counting Kit-8 assay	657:681	Cell Counting Kit-8 assay	657:681	Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay.
30962710	4	67	theme	O-GlcNAcylation	585:599	arg1	effects					574:580	the effects	570:580	the effects of O-GlcNAcylation on RCC cell proliferation in vitro	570:634	Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay.
30962710	8	68	theme	patient	1111:1117	arg1	prognosis					1119:1127	poor patient prognosis	1106:1127	poor patient prognosis	1106:1127	RESULTS O-GlcNAcylation levels and OGT expression were increased in RCC, and the high amounts correlated with poor patient prognosis.
30962710	5	69	from	effects	738:744	arg1	cells					770:774	RCC cells	766:774	RCC cells	766:774	A xenograft assay was performed to assess the in vivo effects of OGT knockdown in RCC cells.
30962710	11	70	used	used	1452:1455	arg2	OGT					1439:1441	OGT	1439:1441	OGT	1439:1441	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	11	70	used	used	1452:1455	arg2	target					1462:1467	a target	1460:1467	a target for RCC therapy in the future	1460:1497	CONCLUSION These findings provide novel insights into the oncogenic roles of O-GlcNAcylation and OGT in the development of RCC, indicating that OGT might be used as a target for RCC therapy in the future.
30962710	4	71	theme	cell	608:611	arg1	proliferation					613:625	RCC cell proliferation	604:625	RCC cell proliferation in vitro	604:634	Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay.
30962710	0	72	theme	EGFR	68:71	arg1	expression					73:82	EGFR expression	68:82	EGFR expression in renal cell carcinoma	68:106	Suppressed OGT expression inhibits cell proliferation and modulates EGFR expression in renal cell carcinoma.
30962710	2	73	theme	cell	357:360	arg1	RCC					373:375	RCC	373:375	RCC	373:375	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	2	73	theme	cell	357:360	arg1	carcinoma					362:370	human renal cell carcinoma	345:370	human renal cell carcinoma (RCC)	345:376	The purpose of the present study was to assess O-GlcNAcylation in human renal cell carcinoma (RCC).
30962710	4	74	theme	RCC	604:606	arg1	proliferation					613:625	RCC cell proliferation	604:625	RCC cell proliferation in vitro	604:634	Then, the effects of O-GlcNAcylation on RCC cell proliferation in vitro were investigated by Cell Counting Kit-8 assay.
30659065	2	0	theme	N-linked	392:399	arg1	glycans					401:407	the N-linked glycans	388:407	the N-linked glycans	388:407	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	12	1	theme	multi-isotype	2004:2016	arg1	approach					2018:2025	This multi-isotype approach	1999:2025	This multi-isotype approach	1999:2025	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	12	1	theme	multi-isotype	2004:2016	arg1	step					2040:2043	a crucial step	2030:2043	a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection	2030:2187	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	3	2	theme	monoclonal	561:570	arg1	therapeutics					572:583	monoclonal therapeutics	561:583	monoclonal therapeutics	561:583	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	7	3	theme	lower	1486:1490	arg1	abundance					1501:1509	a lower relative abundance	1484:1509	a lower relative abundance of G1FB	1484:1517	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	2	4	theme	antibody	300:307	arg1	isotype/subclass					276:291	The isotype/subclass	272:291	The isotype/subclass of the antibody	272:307	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	4	theme	antibody	300:307	arg1	variables					463:471	the known variables	453:471	the known variables within the Fc domain that program antibody effector function	453:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	4	theme	antibody	300:307	arg1	N-glycosylation					331:345	the co-translational N-glycosylation	310:345	the co-translational N-glycosylation on the CH2 domain	310:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	4	theme	antibody	300:307	arg1	remodeling					374:383	the remodeling	370:383	the remodeling of the N-linked glycans during passage through the ER and Golgi	370:447	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	11	5	theme	complex	1889:1895	arg1	glycans					1897:1903	complex glycans	1889:1903	complex glycans	1889:1903	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	12	6	theme	tune	2152:2155	arg1	antibodies					2157:2166	tune antibodies	2152:2166	tune antibodies	2152:2166	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	2	7	gly	N-glycosylation	331:345	arg1	domain					358:363	the CH2 domain	350:363	the CH2 domain	350:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	7	gly	N-glycosylation	331:345	arg1	glycans					401:407	the N-linked glycans	388:407	the N-linked glycans	388:407	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	7	gly	N-glycosylation	331:345	arg1	antibody					300:307	the antibody	296:307	the antibody	296:307	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	8	theme	co-translational	314:329	arg1	isotype/subclass					276:291	The isotype/subclass	272:291	The isotype/subclass of the antibody	272:307	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	8	theme	co-translational	314:329	arg1	variables					463:471	the known variables	453:471	the known variables within the Fc domain that program antibody effector function	453:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	8	theme	co-translational	314:329	arg1	N-glycosylation					331:345	the co-translational N-glycosylation	310:345	the co-translational N-glycosylation on the CH2 domain	310:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	8	theme	co-translational	314:329	arg1	remodeling					374:383	the remodeling	370:383	the remodeling of the N-linked glycans during passage through the ER and Golgi	370:447	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	1	9	theme	immune	216:221	arg1	systems					223:229	the innate and adaptive immune systems	192:229	the innate and adaptive immune systems	192:229	Antibodies are critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection.
30659065	10	10	from	digests	1652:1658	arg1	subset					1679:1684	a subset	1677:1684	a subset of donors	1677:1694	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	6	11	link	N-linked	1315:1322	arg1	repertoire					1331:1340	the site-specific N-linked glycan repertoire	1297:1340	the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors	1297:1405	We simultaneously determined the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors.
30659065	7	12	theme	relative	1452:1459	arg1	abundance					1461:1469	a higher relative abundance	1443:1469	a higher relative abundance of G1S1F	1443:1478	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	12	13	theme	different	2125:2133	arg1	isotypes					2135:2142	different isotypes	2125:2142	different isotypes	2125:2142	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	4	14	dep	five	1001:1004	arg1	to					998:999	to	998:999	to	998:999	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	2	15	theme	CH2	354:356	arg1	domain					358:363	the CH2 domain	350:363	the CH2 domain	350:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	11	16	theme	IgM	1842:1844	arg1	N209					1857:1860	N209	1857:1860	N209	1857:1860	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	16	theme	IgM	1842:1844	arg1	N272					1867:1870	N272	1867:1870	N272	1867:1870	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	16	theme	IgM	1842:1844	arg1	N46					1852:1854	N46	1852:1854	N46	1852:1854	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	16	theme	IgM	1842:1844	arg1	sites					1846:1850	IgM sites	1842:1850	IgM sites N46, N209, and N272	1842:1870	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	1	17	gly	glycoproteins	166:178	arg1	glycoproteins					166:178	critical glycoproteins	157:178	critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection	157:269	Antibodies are critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection.
30659065	1	17	gly	glycoproteins	166:178	arg1	Antibodies					142:151	Antibodies	142:151	Antibodies	142:151	Antibodies are critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection.
30659065	5	18	theme	stepped-energy	1122:1135	arg1	dissociation					1163:1174	stepped-energy higher energy collisional dissociation	1122:1174	stepped-energy higher energy collisional dissociation	1122:1174	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	3	19	theme	monosaccharide	644:657	arg1	residues					659:666	specific monosaccharide residues	635:666	specific monosaccharide residues	635:666	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	4	20	theme	first	951:955	arg1	responders					957:966	the first responders	947:966	the first responders in certain diseases	947:986	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	20	theme	first	951:955	arg1	isotypes					910:917	other antibody isotypes	895:917	other antibody isotypes	895:917	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	6	21	theme	N-linked	1315:1322	arg1	repertoire					1331:1340	the site-specific N-linked glycan repertoire	1297:1340	the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors	1297:1405	We simultaneously determined the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors.
30659065	12	22	theme	disease-specific	2084:2099	arg1	signatures					2110:2119	disease-specific N-glycan signatures	2084:2119	disease-specific N-glycan signatures for different isotypes	2084:2142	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	11	23	theme	higher	1944:1949	arg1	abundances					1960:1969	higher relative abundances	1944:1969	higher relative abundances of high-mannose glycoforms	1944:1996	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	1	24	theme	critical	157:164	arg1	glycoproteins					166:178	critical glycoproteins	157:178	critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection	157:269	Antibodies are critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection.
30659065	1	24	theme	critical	157:164	arg1	Antibodies					142:151	Antibodies	142:151	Antibodies	142:151	Antibodies are critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection.
30659065	2	25	from	N-glycosylation	331:345	arg1	domain					358:363	the CH2 domain	350:363	the CH2 domain	350:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	11	26	theme	glycoforms	1987:1996	arg1	abundances					1960:1969	higher relative abundances	1944:1969	higher relative abundances of high-mannose glycoforms	1944:1996	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	4	27	theme	antibody	1023:1030	arg1	antibody					1023:1030	antibody	1023:1030	antibody	1023:1030	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	27	theme	antibody	1023:1030	arg1	sites/monomer					1006:1018	two to five sites/monomer	994:1018	two to five sites/monomer of antibody	994:1030	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	11	28	theme	high-mannose	1974:1985	arg1	glycoforms					1987:1996	high-mannose glycoforms	1974:1996	high-mannose glycoforms	1974:1996	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	5	29	gly	occupancy	1225:1233	arg2	antibodies					1256:1265	circulating serum antibodies	1238:1265	circulating serum antibodies	1238:1265	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	5	29	gly	occupancy	1225:1233	arg1	antibodies					1256:1265	circulating serum antibodies	1238:1265	circulating serum antibodies	1238:1265	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	5	29	gly	occupancy	1225:1233	arg2	site					1220:1223	site occupancy	1220:1233	site occupancy	1220:1233	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	5	30	theme	N-glycan	1196:1203	arg1	antibodies					1256:1265	circulating serum antibodies	1238:1265	circulating serum antibodies	1238:1265	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	5	30	theme	N-glycan	1196:1203	arg1	repertoire					1205:1214	N-glycan repertoire	1196:1214	N-glycan repertoire	1196:1214	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	4	31	theme	single	845:850	arg1	site					868:871	a single N-glycosylation site	843:871	a single N-glycosylation site	843:871	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	0	32	theme	N-Glycosylation	116:130	arg1	Profiles					132:139	Isotype- and Subclass-Specific N-Glycosylation Profiles	85:139	Isotype- and Subclass-Specific N-Glycosylation Profiles	85:139	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	5	33	theme	energy	1144:1149	arg1	dissociation					1163:1174	stepped-energy higher energy collisional dissociation	1122:1174	stepped-energy higher energy collisional dissociation	1122:1174	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	2	34	theme	Fc	484:485	arg1	domain					487:492	the Fc domain	480:492	the Fc domain that program antibody effector function	480:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	3	35	from	N-glycans	682:690	arg1	removal					624:630	removal	624:630	removal of specific monosaccharide residues from antibody N-glycans	624:690	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	3	35	from	N-glycans	682:690	arg1	addition					612:619	addition	612:619	addition	612:619	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	10	36	theme	sera	1667:1670	arg1	digests					1652:1658	digests	1652:1658	digests of the sera from a subset of donors	1652:1694	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	0	37	theme	Multi-isotype	0:12	arg1	Characterization					29:44	Multi-isotype Glycoproteomic Characterization	0:44	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains	0:75	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	5	38	theme	circulating	1238:1248	arg1	antibodies					1256:1265	circulating serum antibodies	1238:1265	circulating serum antibodies	1238:1265	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	5	39	dep	repertoire	1205:1214	arg1	the					1192:1194	the	1192:1194	the	1192:1194	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	2	40	theme	known	457:461	arg1	isotype/subclass					276:291	The isotype/subclass	272:291	The isotype/subclass of the antibody	272:307	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	40	theme	known	457:461	arg1	variables					463:471	the known variables	453:471	the known variables within the Fc domain that program antibody effector function	453:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	40	theme	known	457:461	arg1	remodeling					374:383	the remodeling	370:383	the remodeling of the N-linked glycans during passage through the ER and Golgi	370:447	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	40	theme	known	457:461	arg1	N-glycosylation					331:345	the co-translational N-glycosylation	310:345	the co-translational N-glycosylation on the CH2 domain	310:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	5	41	theme	antibodies	1256:1265	arg1	occupancy					1225:1233	site occupancy	1220:1233	site occupancy	1220:1233	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	5	41	theme	antibodies	1256:1265	arg1	antibodies					1256:1265	circulating serum antibodies	1238:1265	circulating serum antibodies	1238:1265	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	5	41	theme	antibodies	1256:1265	arg1	repertoire					1205:1214	N-glycan repertoire	1196:1214	N-glycan repertoire	1196:1214	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	2	42	theme	antibody	507:514	arg1	function					525:532	program antibody effector function	499:532	program antibody effector function	499:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	4	43	theme	other	895:899	arg1	responders					957:966	the first responders	947:966	the first responders in certain diseases	947:986	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	43	theme	other	895:899	arg1	isotypes					910:917	other antibody isotypes	895:917	other antibody isotypes	895:917	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	0	44	theme	Serum	49:53	arg1	Chains					70:75	Serum Antibody Heavy Chains	49:75	Serum Antibody Heavy Chains	49:75	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	10	45	theme	unmodified	1712:1721	arg1	peptide					1723:1729	an unmodified peptide	1709:1729	an unmodified peptide containing a proline residue at position 93	1709:1773	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	0	46	theme	Heavy	64:68	arg1	Chains					70:75	Serum Antibody Heavy Chains	49:75	Serum Antibody Heavy Chains	49:75	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	11	47	theme	relative	1951:1958	arg1	abundances					1960:1969	higher relative abundances	1944:1969	higher relative abundances of high-mannose glycoforms	1944:1996	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	3	48	theme	antibodies	721:730	arg1	potency					710:716	the potency	706:716	the potency of antibodies	706:730	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	10	49	theme	proline	1744:1750	arg1	residue					1752:1758	a proline residue	1742:1758	a proline residue	1742:1758	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	4	50	gly	N-glycosylation	852:866	arg2	site					868:871	a single N-glycosylation site	843:871	a single N-glycosylation site	843:871	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	2	51	theme	glycans	401:407	arg1	isotype/subclass					276:291	The isotype/subclass	272:291	The isotype/subclass of the antibody	272:307	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	51	theme	glycans	401:407	arg1	variables					463:471	the known variables	453:471	the known variables within the Fc domain that program antibody effector function	453:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	51	theme	glycans	401:407	arg1	N-glycosylation					331:345	the co-translational N-glycosylation	310:345	the co-translational N-glycosylation on the CH2 domain	310:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	2	51	theme	glycans	401:407	arg1	remodeling					374:383	the remodeling	370:383	the remodeling of the N-linked glycans during passage through the ER and Golgi	370:447	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	10	52	gly	N-glycosylation	1818:1832	arg1	N92					1837:1839	N92	1837:1839	N92	1837:1839	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	2	53	from	remodeling	374:383	arg1	domain					358:363	the CH2 domain	350:363	the CH2 domain	350:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	7	54	theme	G1FB	1514:1517	arg1	abundance					1501:1509	a lower relative abundance	1484:1509	a lower relative abundance of G1FB	1484:1517	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	7	54	theme	G1FB	1514:1517	arg1	abundance					1461:1469	a higher relative abundance	1443:1469	a higher relative abundance of G1S1F	1443:1478	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	7	55	theme	relative	1492:1499	arg1	abundance					1501:1509	a lower relative abundance	1484:1509	a lower relative abundance of G1FB	1484:1517	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	2	56	link	N-linked	392:399	arg1	glycans					401:407	the N-linked glycans	388:407	the N-linked glycans	388:407	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	1	57	theme	adaptive	207:214	arg1	systems					223:229	the innate and adaptive immune systems	192:229	the innate and adaptive immune systems	192:229	Antibodies are critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection.
30659065	3	58	theme	antibody	790:797	arg1	N-glycosylation					799:813	antibody N-glycosylation	790:813	antibody N-glycosylation	790:813	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	7	59	theme	G1S1F	1474:1478	arg1	abundance					1501:1509	a lower relative abundance	1484:1509	a lower relative abundance of G1FB	1484:1517	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	7	59	theme	G1S1F	1474:1478	arg1	abundance					1461:1469	a higher relative abundance	1443:1469	a higher relative abundance of G1S1F	1443:1478	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	4	60	contain	have	838:841	arg2	site					868:871	a single N-glycosylation site	843:871	a single N-glycosylation site	843:871	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	60	contain	have	838:841	arg1	IgGs					825:828	IgGs	825:828	IgGs	825:828	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	61	theme	certain	971:977	arg1	diseases					979:986	certain diseases	971:986	certain diseases	971:986	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	6	62	theme	healthy	1392:1398	arg1	donors					1400:1405	individual healthy donors	1381:1405	individual healthy donors	1381:1405	We simultaneously determined the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors.
30659065	3	63	theme	specific	635:642	arg1	residues					659:666	specific monosaccharide residues	635:666	specific monosaccharide residues	635:666	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	7	64	theme	higher	1445:1450	arg1	abundance					1461:1469	a higher relative abundance	1443:1469	a higher relative abundance of G1S1F	1443:1478	Compared with IgG1, IgG4 displayed a higher relative abundance of G1S1F and a lower relative abundance of G1FB.
30659065	5	65	theme	higher	1137:1142	arg1	dissociation					1163:1174	stepped-energy higher energy collisional dissociation	1122:1174	stepped-energy higher energy collisional dissociation	1122:1174	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	10	66	contain	containing	1731:1740	arg2	residue					1752:1758	a proline residue	1742:1758	a proline residue	1742:1758	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	10	66	contain	containing	1731:1740	arg1	peptide					1723:1729	an unmodified peptide	1709:1729	an unmodified peptide containing a proline residue at position 93	1709:1773	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	6	67	theme	site-specific	1301:1313	arg1	repertoire					1331:1340	the site-specific N-linked glycan repertoire	1297:1340	the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors	1297:1405	We simultaneously determined the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors.
30659065	4	68	from	responders	957:966	arg1	diseases					979:986	certain diseases	971:986	certain diseases	971:986	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	3	69	theme	antibody	673:680	arg1	N-glycans					682:690	antibody N-glycans	673:690	antibody N-glycans	673:690	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	12	70	theme	N-glycan	2101:2108	arg1	signatures					2110:2119	disease-specific N-glycan signatures	2084:2119	disease-specific N-glycan signatures for different isotypes	2084:2142	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	6	71	from	repertoire	1331:1340	arg1	donors					1400:1405	individual healthy donors	1381:1405	individual healthy donors	1381:1405	We simultaneously determined the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors.
30659065	0	72	theme	Isotype-	85:92	arg1	Profiles					132:139	Isotype- and Subclass-Specific N-Glycosylation Profiles	85:139	Isotype- and Subclass-Specific N-Glycosylation Profiles	85:139	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	5	73	theme	nLC-MS/MS	1099:1107	arg1	method					1109:1114	a nLC-MS/MS method	1097:1114	a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies	1097:1265	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	3	74	theme	residues	659:666	arg1	removal					624:630	removal	624:630	removal of specific monosaccharide residues from antibody N-glycans	624:690	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	3	74	theme	residues	659:666	arg1	addition					612:619	addition	612:619	addition	612:619	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30659065	9	75	theme	IgA2	1574:1577	arg1	variants					1579:1586	IgA2 variants	1574:1586	IgA2 variants with the either serine (S93) or proline (P93)	1574:1632	IgA2 variants with the either serine (S93) or proline (P93) were detected.
30659065	8	76	theme	biantennary	1551:1561	arg1	N-glycans					1563:1571	biantennary N-glycans	1551:1571	biantennary N-glycans	1551:1571	IgA1 and IgA2 displayed mostly biantennary N-glycans.
30659065	0	77	theme	Subclass-Specific	98:114	arg1	Profiles					132:139	Isotype- and Subclass-Specific N-Glycosylation Profiles	85:139	Isotype- and Subclass-Specific N-Glycosylation Profiles	85:139	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	1	78	theme	innate	196:201	arg1	systems					223:229	the innate and adaptive immune systems	192:229	the innate and adaptive immune systems	192:229	Antibodies are critical glycoproteins that bridge the innate and adaptive immune systems to provide protection against infection.
30659065	2	79	theme	effector	516:523	arg1	function					525:532	program antibody effector function	499:532	program antibody effector function	499:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	9	80	with	variants	1579:1586	arg1	P93					1629:1631	P93	1629:1631	P93	1629:1631	IgA2 variants with the either serine (S93) or proline (P93) were detected.
30659065	9	80	with	variants	1579:1586	arg1	S93					1612:1614	S93	1612:1614	S93	1612:1614	IgA2 variants with the either serine (S93) or proline (P93) were detected.
30659065	9	80	with	variants	1579:1586	arg1	proline					1620:1626	proline	1620:1626	proline	1620:1626	IgA2 variants with the either serine (S93) or proline (P93) were detected.
30659065	9	80	with	variants	1579:1586	arg1	serine					1604:1609	serine	1604:1609	serine (S93)	1604:1615	IgA2 variants with the either serine (S93) or proline (P93) were detected.
30659065	5	81	theme	collisional	1151:1161	arg1	dissociation					1163:1174	stepped-energy higher energy collisional dissociation	1122:1174	stepped-energy higher energy collisional dissociation	1122:1174	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	4	82	theme	N-glycosylation	852:866	arg1	site					868:871	a single N-glycosylation site	843:871	a single N-glycosylation site	843:871	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	0	83	theme	Glycoproteomic	14:27	arg1	Characterization					29:44	Multi-isotype Glycoproteomic Characterization	0:44	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains	0:75	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	11	84	dep	sites	1846:1850	arg1	N209					1857:1860	N209	1857:1860	N209	1857:1860	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	84	dep	sites	1846:1850	arg1	N272					1867:1870	N272	1867:1870	N272	1867:1870	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	84	dep	sites	1846:1850	arg1	N46					1852:1854	N46	1852:1854	N46	1852:1854	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	84	dep	sites	1846:1850	arg1	sites					1846:1850	IgM sites	1842:1850	IgM sites N46, N209, and N272	1842:1870	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	2	85	from	isotype/subclass	276:291	arg1	domain					358:363	the CH2 domain	350:363	the CH2 domain	350:363	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	5	86	theme	serum	1250:1254	arg1	antibodies					1256:1265	circulating serum antibodies	1238:1265	circulating serum antibodies	1238:1265	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	11	87	dep	displayed	1872:1880	arg1	whereas					1906:1912	whereas	1906:1912	whereas	1906:1912	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	4	88	contain	have	989:992	arg1	responders					957:966	the first responders	947:966	the first responders in certain diseases	947:986	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	88	contain	have	989:992	arg2	antibody					1023:1030	antibody	1023:1030	antibody	1023:1030	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	88	contain	have	989:992	arg2	sites/monomer					1006:1018	two to five sites/monomer	994:1018	two to five sites/monomer of antibody	994:1030	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	88	contain	have	989:992	arg1	isotypes					910:917	other antibody isotypes	895:917	other antibody isotypes	895:917	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	13	89	with	ProteomeXchange	2213:2227	arg1	identifier					2234:2243	identifier PXD010911	2234:2253	identifier PXD010911	2234:2253	Data are available via ProteomeXchange with identifier PXD010911.
30659065	10	90	theme	donors	1689:1694	arg1	subset					1679:1684	a subset	1677:1684	a subset of donors	1677:1694	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	0	91	theme	Antibody	55:62	arg1	Chains					70:75	Serum Antibody Heavy Chains	49:75	Serum Antibody Heavy Chains	49:75	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	2	92	theme	program	499:505	arg1	function					525:532	program antibody effector function	499:532	program antibody effector function	499:532	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	0	93	theme	Chains	70:75	arg1	Characterization					29:44	Multi-isotype Glycoproteomic Characterization	0:44	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains	0:75	Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles.
30659065	5	94	theme	site	1220:1223	arg1	occupancy					1225:1233	site occupancy	1220:1233	site occupancy	1220:1233	Here we employ a nLC-MS/MS method using stepped-energy higher energy collisional dissociation to characterize the N-glycan repertoire and site occupancy of circulating serum antibodies.
30659065	6	95	theme	individual	1381:1390	arg1	donors					1400:1405	individual healthy donors	1381:1405	individual healthy donors	1381:1405	We simultaneously determined the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors.
30659065	4	96	theme	antibody	901:908	arg1	responders					957:966	the first responders	947:966	the first responders in certain diseases	947:986	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	4	96	theme	antibody	901:908	arg1	isotypes					910:917	other antibody isotypes	895:917	other antibody isotypes	895:917	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	11	97	dep	sites	1914:1918	arg1	N279					1920:1923	N279	1920:1923	N279	1920:1923	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	97	dep	sites	1914:1918	arg1	sites					1914:1918	sites N279 and N439	1914:1932	sites N279 and N439	1914:1932	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	11	97	dep	sites	1914:1918	arg1	N439					1929:1932	N439	1929:1932	N439	1929:1932	IgM sites N46, N209, and N272 displayed mostly complex glycans, whereas sites N279 and N439 displayed higher relative abundances of high-mannose glycoforms.
30659065	6	98	theme	glycan	1324:1329	arg1	repertoire					1331:1340	the site-specific N-linked glycan repertoire	1297:1340	the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors	1297:1405	We simultaneously determined the site-specific N-linked glycan repertoire for IgG1, IgG4, IgA1, IgA2, and IgM in individual healthy donors.
30659065	12	99	theme	crucial	2032:2038	arg1	approach					2018:2025	This multi-isotype approach	1999:2025	This multi-isotype approach	1999:2025	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	12	99	theme	crucial	2032:2038	arg1	step					2040:2043	a crucial step	2030:2043	a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection	2030:2187	This multi-isotype approach is a crucial step toward developing a platform to define disease-specific N-glycan signatures for different isotypes to help tune antibodies to induce protection.
30659065	10	100	from	subset	1679:1684	arg1	digests					1652:1658	digests	1652:1658	digests of the sera from a subset of donors	1652:1694	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	10	100	from	subset	1679:1684	arg1	sera					1667:1670	the sera	1663:1670	the sera from a subset of donors	1663:1694	In digests of the sera from a subset of donors, we detected an unmodified peptide containing a proline residue at position 93; this substitution would strongly disfavor N-glycosylation at N92.
30659065	4	101	dep	IgA	925:927	arg1	e.g.					920:923	e.g.	920:923	e.g.	920:923	Although IgGs usually have a single N-glycosylation site and are well studied, other antibody isotypes, e.g. IgA and IgM, that are the first responders in certain diseases, have two to five sites/monomer of antibody, and little is known about their N-glycosylation.
30659065	2	102	dep	ER	436:437	arg1	the					432:434	the	432:434	the	432:434	The isotype/subclass of the antibody, the co-translational N-glycosylation on the CH2 domain, and the remodeling of the N-linked glycans during passage through the ER and Golgi are the known variables within the Fc domain that program antibody effector function.
30659065	3	103	theme	therapeutics	572:583	arg1	investigations					543:556	investigations	543:556	investigations of monoclonal therapeutics	543:583	Through investigations of monoclonal therapeutics, it has been observed that addition or removal of specific monosaccharide residues from antibody N-glycans can influence the potency of antibodies, highlighting the importance of thoroughly characterizing antibody N-glycosylation.
30355725	6	0	theme	effects	951:957	arg1	range					938:942	the spatial range	926:942	the spatial range of Sog effects in the tissue	926:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	4	1	dep	range	418:422	arg1	The					414:416	The	414:416	The	414:416	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	6	2	from	effects	951:957	arg1	tissue					966:971	the tissue	962:971	the tissue	962:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	6	3	theme	Sog	947:949	arg1	effects					951:957	Sog effects	947:957	Sog effects in the tissue	947:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	6	4	theme	Sog	861:863	arg1	sites					879:883	individual Sog glycosylation sites	850:883	individual Sog glycosylation sites	850:883	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	5	5	theme	conserved	612:620	arg1	gastrulation					657:668	the conserved extracellular BMP antagonist Short gastrulation	608:668	the conserved extracellular BMP antagonist Short gastrulation (Sog)	608:674	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	5	5	theme	conserved	612:620	arg1	Sog					671:673	Sog	671:673	Sog	671:673	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	8	6	theme	conserved	1227:1235	arg1	process					1237:1243	an evolutionarily conserved process	1209:1243	an evolutionarily conserved process that adds complexity to the regulation of BMP activity	1209:1298	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	8	6	theme	conserved	1227:1235	arg1	N-glycosylation					1186:1200	N-glycosylation	1186:1200	N-glycosylation	1186:1200	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	4	7	theme	protein	494:500	arg1	complexes					502:510	glycosylated protein complexes	481:510	glycosylated protein complexes in the extracellular milieu	481:538	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	6	8	theme	pathway	778:784	arg1	activity					786:793	BMP pathway activity	774:793	BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue	774:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	5	9	theme	extracellular	622:634	arg1	gastrulation					657:668	the conserved extracellular BMP antagonist Short gastrulation	608:668	the conserved extracellular BMP antagonist Short gastrulation (Sog)	608:674	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	5	9	theme	extracellular	622:634	arg1	Sog					671:673	Sog	671:673	Sog	671:673	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	6	10	gly	glycosylation	865:877	arg2	sites					879:883	individual Sog glycosylation sites	850:883	individual Sog glycosylation sites	850:883	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	8	11	from	proteins	1163:1170	arg1	identification					1106:1119	The identification	1102:1119	The identification of similar residues in vertebrate Chordin proteins	1102:1170	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	3	12	theme	dynamic	346:352	arg1	complexes					354:362	highly dynamic complexes	339:362	highly dynamic complexes	339:362	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	3	12	theme	dynamic	346:352	arg1	proteins					316:323	Bone morphogenetic proteins	297:323	Bone morphogenetic proteins (BMPs)	297:330	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	4	13	theme	glycosylated	481:492	arg1	complexes					502:510	glycosylated protein complexes	481:510	glycosylated protein complexes in the extracellular milieu	481:538	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	5	14	theme	antagonist	640:649	arg1	gastrulation					657:668	the conserved extracellular BMP antagonist Short gastrulation	608:668	the conserved extracellular BMP antagonist Short gastrulation (Sog)	608:674	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	5	14	theme	antagonist	640:649	arg1	Sog					671:673	Sog	671:673	Sog	671:673	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	0	15	link	N-linked	0:7	arg1	glycosylation					9:21	N-linked glycosylation	0:21	N-linked glycosylation	0:21	N-linked glycosylation restricts the function of Short gastrulation to bind and shuttle BMPs.
30355725	6	16	from	effect	737:742	arg1	activity					786:793	BMP pathway activity	774:793	BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue	774:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	8	17	theme	activity	1291:1298	arg1	regulation					1273:1282	the regulation	1269:1282	the regulation of BMP activity	1269:1298	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	4	18	from	complexes	502:510	arg1	milieu					533:538	the extracellular milieu	515:538	the extracellular milieu	515:538	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	4	19	with	interactions	463:474	arg1	complexes					502:510	glycosylated protein complexes	481:510	glycosylated protein complexes in the extracellular milieu	481:538	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	6	20	dep	Drosophila	798:807	arg1	reveals					829:835	reveals	829:835	reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue	829:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	5	21	theme	gastrulation	657:668	arg1	function					596:603	the function	592:603	the function of the conserved extracellular BMP antagonist Short gastrulation (Sog)	592:674	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	6	22	theme	Functional	809:818	arg1	analysis					820:827	Functional analysis	809:827	Functional analysis	809:827	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	6	23	theme	spatial	930:936	arg1	range					938:942	the spatial range	926:942	the spatial range of Sog effects in the tissue	926:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	0	24	theme	N-linked	0:7	arg1	glycosylation					9:21	N-linked glycosylation	0:21	N-linked glycosylation	0:21	N-linked glycosylation restricts the function of Short gastrulation to bind and shuttle BMPs.
30355725	6	25	theme	individual	850:859	arg1	sites					879:883	individual Sog glycosylation sites	850:883	individual Sog glycosylation sites	850:883	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	4	26	gly	glycosylated	481:492	arg1	complexes					502:510	glycosylated protein complexes	481:510	glycosylated protein complexes in the extracellular milieu	481:538	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	3	27	theme	several	376:382	arg1	functions					384:392	several functions	376:392	several functions	376:392	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	5	28	theme	BMP	636:638	arg1	gastrulation					657:668	the conserved extracellular BMP antagonist Short gastrulation	608:668	the conserved extracellular BMP antagonist Short gastrulation (Sog)	608:674	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	5	28	theme	BMP	636:638	arg1	Sog					671:673	Sog	671:673	Sog	671:673	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	6	29	theme	N-glycosylated	699:712	arg1	sites					714:718	conserved N-glycosylated sites	689:718	conserved N-glycosylated sites	689:718	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	7	30	theme	Sog	1073:1075	arg1	levels					1077:1082	extracellular Sog levels	1059:1082	extracellular Sog levels	1059:1082	Mechanistically, we provide evidence that N-terminal and stem glycosylation controls extracellular Sog levels and distribution.
30355725	3	31	theme	Bone	297:300	arg1	proteins					316:323	Bone morphogenetic proteins	297:323	Bone morphogenetic proteins (BMPs)	297:330	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	3	31	theme	Bone	297:300	arg1	complexes					354:362	highly dynamic complexes	339:362	highly dynamic complexes	339:362	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	3	31	theme	Bone	297:300	arg1	BMPs					326:329	BMPs	326:329	BMPs	326:329	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	6	32	gly	N-glycosylated	699:712	arg1	sites					714:718	conserved N-glycosylated sites	689:718	conserved N-glycosylated sites	689:718	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	6	33	theme	conserved	689:697	arg1	sites					714:718	conserved N-glycosylated sites	689:718	conserved N-glycosylated sites	689:718	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	8	34	theme	BMP	1287:1289	arg1	activity					1291:1298	BMP activity	1287:1298	BMP activity	1287:1298	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	8	35	theme	Chordin	1155:1161	arg1	proteins					1163:1170	vertebrate Chordin proteins	1144:1170	vertebrate Chordin proteins	1144:1170	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	2	36	theme	developmental	236:248	arg1	defects					268:274	the associated developmental and physiological defects	221:274	the associated developmental and physiological defects	221:274	However, the targets that are responsible for the associated developmental and physiological defects are largely unknown.
30355725	8	37	theme	vertebrate	1144:1153	arg1	proteins					1163:1170	vertebrate Chordin proteins	1144:1170	vertebrate Chordin proteins	1144:1170	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	6	38	theme	BMP	894:896	arg1	antagonism					898:907	BMP antagonism	894:907	BMP antagonism	894:907	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	2	39	theme	associated	225:234	arg1	defects					268:274	the associated developmental and physiological defects	221:274	the associated developmental and physiological defects	221:274	However, the targets that are responsible for the associated developmental and physiological defects are largely unknown.
30355725	7	40	theme	extracellular	1059:1071	arg1	levels					1077:1082	extracellular Sog levels	1059:1082	extracellular Sog levels	1059:1082	Mechanistically, we provide evidence that N-terminal and stem glycosylation controls extracellular Sog levels and distribution.
30355725	0	41	theme	gastrulation	55:66	arg1	function					37:44	the function	33:44	the function of Short gastrulation to bind and shuttle BMPs	33:91	N-linked glycosylation restricts the function of Short gastrulation to bind and shuttle BMPs.
30355725	6	42	from	tissue	966:971	arg1	range					938:942	the spatial range	926:942	the spatial range of Sog effects in the tissue	926:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	3	43	theme	morphogenetic	302:314	arg1	proteins					316:323	Bone morphogenetic proteins	297:323	Bone morphogenetic proteins (BMPs)	297:330	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	3	43	theme	morphogenetic	302:314	arg1	complexes					354:362	highly dynamic complexes	339:362	highly dynamic complexes	339:362	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	3	43	theme	morphogenetic	302:314	arg1	BMPs					326:329	BMPs	326:329	BMPs	326:329	Bone morphogenetic proteins (BMPs) act as highly dynamic complexes to regulate several functions during development.
30355725	1	44	theme	N-linked	107:114	arg1	glycosylation					116:128	N-linked glycosylation	107:128	N-linked glycosylation	107:128	Disorders of N-linked glycosylation are increasingly reported in the literature.
30355725	0	45	theme	Short	49:53	arg1	gastrulation					55:66	Short gastrulation	49:66	Short gastrulation	49:66	N-linked glycosylation restricts the function of Short gastrulation to bind and shuttle BMPs.
30355725	8	46	from	identification	1106:1119	arg1	proteins					1163:1170	vertebrate Chordin proteins	1144:1170	vertebrate Chordin proteins	1144:1170	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	6	47	theme	sites	879:883	arg1	loss					842:845	loss	842:845	loss of individual Sog glycosylation sites	842:883	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	5	48	theme	Short	651:655	arg1	gastrulation					657:668	the conserved extracellular BMP antagonist Short gastrulation	608:668	the conserved extracellular BMP antagonist Short gastrulation (Sog)	608:674	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	5	48	theme	Short	651:655	arg1	Sog					671:673	Sog	671:673	Sog	671:673	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	6	49	theme	BMP	774:776	arg1	activity					786:793	BMP pathway activity	774:793	BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue	774:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	1	50	theme	glycosylation	116:128	arg1	Disorders					94:102	Disorders	94:102	Disorders of N-linked glycosylation	94:128	Disorders of N-linked glycosylation are increasingly reported in the literature.
30355725	1	51	link	N-linked	107:114	arg1	glycosylation					116:128	N-linked glycosylation	107:128	N-linked glycosylation	107:128	Disorders of N-linked glycosylation are increasingly reported in the literature.
30355725	6	52	theme	glycosylation	865:877	arg1	sites					879:883	individual Sog glycosylation sites	850:883	individual Sog glycosylation sites	850:883	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	6	53	from	range	938:942	arg1	tissue					966:971	the tissue	962:971	the tissue	962:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	5	54	theme	glycosylation	574:586	arg1	role					566:569	the role	562:569	the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog)	562:674	Here, we investigate the role of glycosylation for the function of the conserved extracellular BMP antagonist Short gastrulation (Sog).
30355725	6	55	from	activity	786:793	arg1	Drosophila					798:807	Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue	798:971	Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue	798:971	We identify conserved N-glycosylated sites and describe the effect of mutating these residues on BMP pathway activity in Drosophila Functional analysis reveals that loss of individual Sog glycosylation sites enhances BMP antagonism and/or increases the spatial range of Sog effects in the tissue.
30355725	8	56	theme	residues	1132:1139	arg1	identification					1106:1119	The identification	1102:1119	The identification of similar residues in vertebrate Chordin proteins	1102:1170	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	4	57	theme	activity	444:451	arg1	strength					428:435	strength	428:435	strength	428:435	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	4	57	theme	activity	444:451	arg1	range					418:422	range	418:422	range	418:422	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	4	58	theme	BMP	440:442	arg1	activity					444:451	BMP activity	440:451	BMP activity	440:451	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	2	59	theme	physiological	254:266	arg1	defects					268:274	the associated developmental and physiological defects	221:274	the associated developmental and physiological defects	221:274	However, the targets that are responsible for the associated developmental and physiological defects are largely unknown.
30355725	7	60	theme	stem	1031:1034	arg1	glycosylation					1036:1048	stem glycosylation	1031:1048	stem glycosylation	1031:1048	Mechanistically, we provide evidence that N-terminal and stem glycosylation controls extracellular Sog levels and distribution.
30355725	4	61	theme	extracellular	519:531	arg1	milieu					533:538	the extracellular milieu	515:538	the extracellular milieu	515:538	The range and strength of BMP activity depend on interactions with glycosylated protein complexes in the extracellular milieu.
30355725	8	62	theme	similar	1124:1130	arg1	residues					1132:1139	similar residues	1124:1139	similar residues in vertebrate Chordin proteins	1124:1170	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
30355725	8	63	from	residues	1132:1139	arg1	proteins					1163:1170	vertebrate Chordin proteins	1144:1170	vertebrate Chordin proteins	1144:1170	The identification of similar residues in vertebrate Chordin proteins suggests that N-glycosylation may be an evolutionarily conserved process that adds complexity to the regulation of BMP activity.
31787178	4	0	theme	anammox	606:612	arg1	sludge					623:628	anammox granular sludge	606:628	anammox granular sludge in treating low-strength municipal sewage	606:670	In this study, the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings was investigated.
31787178	4	1	theme	sludge	623:628	arg1	robustness					592:601	the robustness	588:601	the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings	588:699	In this study, the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings was investigated.
31787178	9	2	theme	structural	1484:1493	arg1	analyses					1495:1502	structural analyses	1484:1502	structural analyses	1484:1502	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	1	3	theme	anammox	177:183	arg1	application					162:172	the increasing application	147:172	the increasing application of anammox for the treatment of high-strength industrial wastewater	147:240	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	2	4	from	enrichment	365:374	arg1	systems					440:446	municipal sewage treatment systems	413:446	municipal sewage treatment systems	413:446	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	2	5	theme	Sludge	319:324	arg1	granulation					326:336	Sludge granulation	319:336	Sludge granulation in particular	319:350	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	2	6	from	retention	380:388	arg1	systems					440:446	municipal sewage treatment systems	413:446	municipal sewage treatment systems	413:446	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	6	7	theme	insufficient	1167:1178	arg1	source					1187:1192	insufficient carbon source	1167:1192	insufficient carbon source	1167:1192	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	5	8	theme	anaerobic	749:757	arg1	reactor					781:787	an upflow anaerobic sludge blanket (UASB) reactor	739:787	an upflow anaerobic sludge blanket (UASB) reactor with anammox granules	739:809	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	4	9	theme	shock	686:690	arg1	loadings					692:699	various shock loadings	678:699	various shock loadings	678:699	In this study, the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings was investigated.
31787178	10	10	theme	Scanning	1688:1695	arg1	SEM					1718:1720	SEM	1718:1720	SEM	1718:1720	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	10	10	theme	Scanning	1688:1695	arg1	microscopy					1706:1715	Scanning electron microscopy	1688:1715	Scanning electron microscopy (SEM)	1688:1721	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	5	11	theme	blanket	766:772	arg1	reactor					781:787	an upflow anaerobic sludge blanket (UASB) reactor	739:787	an upflow anaerobic sludge blanket (UASB) reactor with anammox granules	739:809	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	5	12	theme	anti-loading	889:900	arg1	capability					908:917	anti-loading shock capability	889:917	anti-loading shock capability	889:917	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	8	13	theme	network	1323:1329	arg1	analyses					1331:1338	molecular ecological network analyses	1302:1338	molecular ecological network analyses	1302:1338	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	6	14	theme	accumulation	976:987	arg1	times					1055:1059	times	1055:1059	times	1055:1059	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	6	14	theme	accumulation	976:987	arg1	rate					989:992	The accumulation rate	972:992	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase	972:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	10	15	theme	granules	1888:1895	arg1	efficient					1844:1852	efficient	1844:1852	efficient	1844:1852	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	9	16	theme	functional	1550:1559	arg1	component					1561:1569	an important functional component	1537:1569	an important functional component	1537:1569	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	16	theme	functional	1550:1559	arg1	polysaccharides					1516:1530	polysaccharides	1516:1530	polysaccharides	1516:1530	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	16	theme	functional	1550:1559	arg1	layer					1661:1665	the major EPS layer	1647:1665	the major EPS layer of anammox granules	1647:1685	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	5	17	theme	anammox	794:800	arg1	granules					802:809	anammox granules	794:809	anammox granules	794:809	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	9	18	theme	extracellular	1592:1604	arg1	TB-EPS					1628:1633	TB-EPS	1628:1633	TB-EPS	1628:1633	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	18	theme	extracellular	1592:1604	arg1	substances					1616:1625	the tightly bound extracellular polymeric substances	1574:1625	the tightly bound extracellular polymeric substances (TB-EPS)	1574:1634	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	0	19	theme	shock	81:85	arg1	loadings					87:94	various shock loadings	73:94	various shock loadings	73:94	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	5	20	theme	8-month	948:954	arg1	period					964:969	the 8-month testing period	944:969	the 8-month testing period	944:969	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	2	21	from	granulation	326:336	arg1	particular					341:350	particular	341:350	particular	341:350	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	6	22	theme	liquid	1032:1037	arg1	phase					1039:1043	the liquid phase	1028:1043	the liquid phase	1028:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	8	23	theme	community	1384:1392	arg1	structure					1394:1402	community structure	1384:1402	community structure	1384:1402	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	5	24	theme	UASB	775:778	arg1	reactor					781:787	an upflow anaerobic sludge blanket (UASB) reactor	739:787	an upflow anaerobic sludge blanket (UASB) reactor with anammox granules	739:809	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	2	25	theme	municipal	413:421	arg1	systems					440:446	municipal sewage treatment systems	413:446	municipal sewage treatment systems	413:446	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	7	26	theme	small	1211:1215	arg1	part					1217:1220	only a small part	1204:1220	only a small part of the produced N2O	1204:1240	However, only a small part of the produced N2O escaped into the atmosphere.
31787178	6	27	dep	times	1055:1059	arg1	higher					1061:1066	higher	1061:1066	higher	1061:1066	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	6	28	from	phase	1039:1043	arg1	times					1055:1059	times	1055:1059	times	1055:1059	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	6	28	from	phase	1039:1043	arg1	rate					989:992	The accumulation rate	972:992	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase	972:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	0	29	theme	various	73:79	arg1	loadings					87:94	various shock loadings	73:94	various shock loadings	73:94	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	2	30	theme	bacteria	401:408	arg1	retention					380:388	retention	380:388	retention	380:388	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	2	30	theme	bacteria	401:408	arg1	enrichment					365:374	enrichment	365:374	enrichment	365:374	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	6	31	theme	gas	1085:1087	arg1	phase					1089:1093	the gas phase	1081:1093	the gas phase	1081:1093	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	5	32	dep	187.2 L/day	925:935	arg1	up					919:920	up	919:920	up	919:920	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	3	33	theme	sludge	486:491	arg1	performance					462:472	the performance	458:472	the performance of granular sludge under continuous and varying hydraulic loading shock	458:544	However, the performance of granular sludge under continuous and varying hydraulic loading shock remains little understood.
31787178	0	34	theme	anammox	14:20	arg1	sewage					60:65	anammox granular sludge treating low-strength sewage	14:65	anammox granular sludge treating low-strength sewage	14:65	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	9	35	theme	major	1651:1655	arg1	component					1561:1569	an important functional component	1537:1569	an important functional component	1537:1569	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	35	theme	major	1651:1655	arg1	polysaccharides					1516:1530	polysaccharides	1516:1530	polysaccharides	1516:1530	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	35	theme	major	1651:1655	arg1	layer					1661:1665	the major EPS layer	1647:1665	the major EPS layer of anammox granules	1647:1685	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	8	36	theme	loading	1449:1455	arg1	shock					1457:1461	loading shock	1449:1461	loading shock	1449:1461	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	2	37	theme	treatment	430:438	arg1	systems					440:446	municipal sewage treatment systems	413:446	municipal sewage treatment systems	413:446	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	0	38	theme	sludge	31:36	arg1	sewage					60:65	anammox granular sludge treating low-strength sewage	14:65	anammox granular sludge treating low-strength sewage	14:65	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	6	39	from	rate	989:992	arg1	phase					1039:1043	the liquid phase	1028:1043	the liquid phase	1028:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	3	40	theme	varying	514:520	arg1	shock					540:544	continuous and varying hydraulic loading shock	499:544	continuous and varying hydraulic loading shock	499:544	However, the performance of granular sludge under continuous and varying hydraulic loading shock remains little understood.
31787178	5	41	theme	anammox	832:838	arg1	activity					849:856	anammox specific activity	832:856	anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period	832:969	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	9	42	theme	anammox	1670:1676	arg1	granules					1678:1685	anammox granules	1670:1685	anammox granules	1670:1685	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	6	43	theme	incomplete	1136:1145	arg1	denitrification					1147:1161	the incomplete denitrification	1132:1161	the incomplete denitrification	1132:1161	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	6	44	from	N2O	997:999	arg1	phase					1039:1043	the liquid phase	1028:1043	the liquid phase	1028:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	3	45	theme	continuous	499:508	arg1	shock					540:544	continuous and varying hydraulic loading shock	499:544	continuous and varying hydraulic loading shock	499:544	However, the performance of granular sludge under continuous and varying hydraulic loading shock remains little understood.
31787178	1	46	theme	wastewater	231:240	arg1	treatment					193:201	the treatment	189:201	the treatment of high-strength industrial wastewater	189:240	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	2	47	theme	sewage	423:428	arg1	systems					440:446	municipal sewage treatment systems	413:446	municipal sewage treatment systems	413:446	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	0	48	dep	Robustness	0:9	arg1	emission					132:139	little N2O emission	121:139	little N2O emission	121:139	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	0	48	dep	Robustness	0:9	arg1	mechanism					107:115	Microbial mechanism	97:115	Microbial mechanism	97:115	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	4	49	theme	low-strength	642:653	arg1	sewage					665:670	low-strength municipal sewage	642:670	low-strength municipal sewage	642:670	In this study, the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings was investigated.
31787178	3	50	theme	loading	532:538	arg1	shock					540:544	continuous and varying hydraulic loading shock	499:544	continuous and varying hydraulic loading shock	499:544	However, the performance of granular sludge under continuous and varying hydraulic loading shock remains little understood.
31787178	1	51	theme	anammox	258:264	arg1	application					243:253	application	243:253	application of anammox in municipal sewage	243:284	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	10	52	from	anammox-clusters	1764:1779	arg1	granules					1788:1795	the granules	1784:1795	the granules	1784:1795	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	1	53	theme	municipal	269:277	arg1	sewage					279:284	municipal sewage	269:284	municipal sewage	269:284	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	9	54	theme	polymeric	1606:1614	arg1	TB-EPS					1628:1633	TB-EPS	1628:1633	TB-EPS	1628:1633	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	54	theme	polymeric	1606:1614	arg1	substances					1616:1625	the tightly bound extracellular polymeric substances	1574:1625	the tightly bound extracellular polymeric substances (TB-EPS)	1574:1634	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	4	55	theme	granular	614:621	arg1	sludge					623:628	anammox granular sludge	606:628	anammox granular sludge in treating low-strength municipal sewage	606:670	In this study, the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings was investigated.
31787178	5	56	theme	shock	902:906	arg1	capability					908:917	anti-loading shock capability	889:917	anti-loading shock capability	889:917	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	0	57	theme	low-strength	47:58	arg1	sewage					60:65	anammox granular sludge treating low-strength sewage	14:65	anammox granular sludge treating low-strength sewage	14:65	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	7	58	theme	produced	1229:1236	arg1	N2O					1238:1240	the produced N2O	1225:1240	the produced N2O	1225:1240	However, only a small part of the produced N2O escaped into the atmosphere.
31787178	9	59	from	component	1561:1569	arg1	TB-EPS					1628:1633	TB-EPS	1628:1633	TB-EPS	1628:1633	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	59	from	component	1561:1569	arg1	substances					1616:1625	the tightly bound extracellular polymeric substances	1574:1625	the tightly bound extracellular polymeric substances (TB-EPS)	1574:1634	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	6	60	theme	carbon	1180:1185	arg1	source					1187:1192	insufficient carbon source	1167:1192	insufficient carbon source	1167:1192	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	0	61	theme	N2O	128:130	arg1	emission					132:139	little N2O emission	121:139	little N2O emission	121:139	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	10	62	theme	sludge	1826:1831	arg1	flotation					1809:1817	the flotation	1805:1817	the flotation of the sludge	1805:1831	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	5	63	theme	0.28 kg N/kg	864:875	arg1	VSS/day					877:883	0.28 kg N/kg VSS/day	864:883	0.28 kg N/kg VSS/day	864:883	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	6	64	theme	<0.01 kg N/kg	1002:1014	arg1	N2O					997:999	N2O	997:999	N2O (<0.01 kg N/kg VSS/day) in the liquid phase	997:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	6	64	theme	<0.01 kg N/kg	1002:1014	arg1	VSS/day					1016:1022	<0.01 kg N/kg VSS/day	1002:1022	<0.01 kg N/kg VSS/day	1002:1022	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	8	65	theme	High-throughput	1271:1285	arg1	sequencing					1287:1296	High-throughput sequencing	1271:1296	High-throughput sequencing	1271:1296	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	10	66	theme	electron	1697:1704	arg1	SEM					1718:1720	SEM	1718:1720	SEM	1718:1720	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	10	66	theme	electron	1697:1704	arg1	microscopy					1706:1715	Scanning electron microscopy	1688:1715	Scanning electron microscopy (SEM)	1688:1721	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	5	67	theme	sludge	759:764	arg1	reactor					781:787	an upflow anaerobic sludge blanket (UASB) reactor	739:787	an upflow anaerobic sludge blanket (UASB) reactor with anammox granules	739:809	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	1	68	theme	high-strength	206:218	arg1	wastewater					231:240	high-strength industrial wastewater	206:240	high-strength industrial wastewater	206:240	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	6	69	theme	N2O	997:999	arg1	times					1055:1059	times	1055:1059	times	1055:1059	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	6	69	theme	N2O	997:999	arg1	rate					989:992	The accumulation rate	972:992	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase	972:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	5	70	with	reactor	781:787	arg1	granules					802:809	anammox granules	794:809	anammox granules	794:809	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	4	71	theme	various	678:684	arg1	loadings					692:699	various shock loadings	678:699	various shock loadings	678:699	In this study, the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings was investigated.
31787178	1	72	from	application	243:253	arg1	sewage					279:284	municipal sewage	269:284	municipal sewage	269:284	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	5	73	theme	testing	956:962	arg1	period					964:969	the 8-month testing period	944:969	the 8-month testing period	944:969	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	5	74	theme	upflow	742:747	arg1	reactor					781:787	an upflow anaerobic sludge blanket (UASB) reactor	739:787	an upflow anaerobic sludge blanket (UASB) reactor with anammox granules	739:809	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	8	75	theme	ecological	1312:1321	arg1	analyses					1331:1338	molecular ecological network analyses	1302:1338	molecular ecological network analyses	1302:1338	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	7	76	theme	N2O	1238:1240	arg1	part					1217:1220	only a small part	1204:1220	only a small part of the produced N2O	1204:1240	However, only a small part of the produced N2O escaped into the atmosphere.
31787178	10	77	theme	anammox	1880:1886	arg1	granules					1888:1895	anammox granules	1880:1895	anammox granules	1880:1895	Scanning electron microscopy (SEM) also showed that the gaps in between the anammox-clusters in the granules inhibit the flotation of the sludge and ensure efficient settling and retention of anammox granules.
31787178	9	78	theme	bound	1586:1590	arg1	TB-EPS					1628:1633	TB-EPS	1628:1633	TB-EPS	1628:1633	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	78	theme	bound	1586:1590	arg1	substances					1616:1625	the tightly bound extracellular polymeric substances	1574:1625	the tightly bound extracellular polymeric substances (TB-EPS)	1574:1634	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	6	79	theme	seven	1049:1053	arg1	times					1055:1059	times	1055:1059	times	1055:1059	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	6	79	theme	seven	1049:1053	arg1	rate					989:992	The accumulation rate	972:992	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase	972:1043	The accumulation rate of N2O (<0.01 kg N/kg VSS/day) in the liquid phase was seven times higher than that of the gas phase, which could be mainly attributed to the incomplete denitrification and insufficient carbon source.
31787178	1	80	theme	increasing	151:160	arg1	application					162:172	the increasing application	147:172	the increasing application of anammox for the treatment of high-strength industrial wastewater	147:240	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	0	81	theme	little	121:126	arg1	emission					132:139	little N2O emission	121:139	little N2O emission	121:139	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	8	82	theme	bacterial	1360:1368	arg1	diversity					1370:1378	the bacterial diversity	1356:1378	the bacterial diversity	1356:1378	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	0	83	theme	Microbial	97:105	arg1	mechanism					107:115	Microbial mechanism	97:115	Microbial mechanism	97:115	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	2	84	dep	enrichment	365:374	arg1	the					361:363	the	361:363	the	361:363	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	5	85	theme	specific	840:847	arg1	activity					849:856	anammox specific activity	832:856	anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period	832:969	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
31787178	2	86	theme	anammox	393:399	arg1	bacteria					401:408	anammox bacteria	393:408	anammox bacteria	393:408	Sludge granulation in particular enhances the enrichment and retention of anammox bacteria in municipal sewage treatment systems.
31787178	0	87	theme	granular	22:29	arg1	sewage					60:65	anammox granular sludge treating low-strength sewage	14:65	anammox granular sludge treating low-strength sewage	14:65	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	8	88	theme	potential	1420:1428	arg1	resistance					1430:1439	the potential resistance	1416:1439	the potential resistance against loading shock	1416:1461	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	0	89	theme	treating	38:45	arg1	sewage					60:65	anammox granular sludge treating low-strength sewage	14:65	anammox granular sludge treating low-strength sewage	14:65	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	1	90	theme	more	303:306	arg1	attention					308:316	more attention	303:316	more attention	303:316	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	8	91	theme	molecular	1302:1310	arg1	analyses					1331:1338	molecular ecological network analyses	1302:1338	molecular ecological network analyses	1302:1338	High-throughput sequencing and molecular ecological network analyses also identified the bacterial diversity and community structure, indicating the potential resistance against loading shock.
31787178	9	92	theme	EPS	1657:1659	arg1	component					1561:1569	an important functional component	1537:1569	an important functional component	1537:1569	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	92	theme	EPS	1657:1659	arg1	polysaccharides					1516:1530	polysaccharides	1516:1530	polysaccharides	1516:1530	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	92	theme	EPS	1657:1659	arg1	layer					1661:1665	the major EPS layer	1647:1665	the major EPS layer of anammox granules	1647:1685	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	3	93	theme	granular	477:484	arg1	sludge					486:491	granular sludge	477:491	granular sludge	477:491	However, the performance of granular sludge under continuous and varying hydraulic loading shock remains little understood.
31787178	0	94	theme	sewage	60:65	arg1	Robustness					0:9	Robustness	0:9	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.	0:140	Robustness of anammox granular sludge treating low-strength sewage under various shock loadings: Microbial mechanism and little N2O emission.
31787178	9	95	theme	important	1540:1548	arg1	component					1561:1569	an important functional component	1537:1569	an important functional component	1537:1569	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	95	theme	important	1540:1548	arg1	polysaccharides					1516:1530	polysaccharides	1516:1530	polysaccharides	1516:1530	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	95	theme	important	1540:1548	arg1	layer					1661:1665	the major EPS layer	1647:1665	the major EPS layer of anammox granules	1647:1685	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	3	96	theme	hydraulic	522:530	arg1	shock					540:544	continuous and varying hydraulic loading shock	499:544	continuous and varying hydraulic loading shock	499:544	However, the performance of granular sludge under continuous and varying hydraulic loading shock remains little understood.
31787178	9	97	theme	granules	1678:1685	arg1	component					1561:1569	an important functional component	1537:1569	an important functional component	1537:1569	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	97	theme	granules	1678:1685	arg1	polysaccharides					1516:1530	polysaccharides	1516:1530	polysaccharides	1516:1530	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	9	97	theme	granules	1678:1685	arg1	layer					1661:1665	the major EPS layer	1647:1665	the major EPS layer of anammox granules	1647:1685	The composition and structural analyses showed that polysaccharides were an important functional component in the tightly bound extracellular polymeric substances (TB-EPS), which was the major EPS layer of anammox granules.
31787178	1	98	theme	industrial	220:229	arg1	wastewater					231:240	high-strength industrial wastewater	206:240	high-strength industrial wastewater	206:240	With the increasing application of anammox for the treatment of high-strength industrial wastewater, application of anammox in municipal sewage has been gaining more attention.
31787178	4	99	theme	municipal	655:663	arg1	sewage					665:670	low-strength municipal sewage	642:670	low-strength municipal sewage	642:670	In this study, the robustness of anammox granular sludge in treating low-strength municipal sewage under various shock loadings was investigated.
31787178	5	100	dep	VSS/day	877:883	arg1	up					858:859	up	858:859	up	858:859	Results showed that an upflow anaerobic sludge blanket (UASB) reactor with anammox granules performed well, with anammox specific activity up to 0.28 kg N/kg VSS/day and anti-loading shock capability up to 187.2 L/day during the 8-month testing period.
30888807	8	0	theme	%	1185:1185	arg1	%					1190:1190	131%/123%	1182:1190	131%/123% (1 mg/L)	1182:1199	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	8	0	theme	%	1185:1185	arg1	mg/L					1195:1198	1 mg/L	1193:1198	1 mg/L	1193:1198	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	5	1	dep	dehydrogenase	826:838	arg1	e.g.					812:815	e.g.	812:815	e.g.	812:815	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	3	2	theme	high	681:684	arg1	sequencing					697:706	high throughput sequencing	681:706	high throughput sequencing	681:706	Additionally, the response of the microbial community structure was examined by high throughput sequencing.
30888807	2	3	theme	P25	350:352	arg1	acute-toxicities					315:330	the acute-toxicities	311:330	the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge	311:402	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	2	3	theme	P25	350:352	arg1	exposure					337:344	8-h exposure	333:344	8-h exposure	333:344	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	9	4	theme	stronger	1492:1499	arg1	attachment					1501:1510	stronger attachment	1492:1510	stronger attachment onto phospholipids	1492:1529	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	12	5	theme	Pearson	1936:1942	arg1	coefficients					1956:1967	High Pearson correlation coefficients	1931:1967	High Pearson correlation coefficients	1931:1967	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	12	6	theme	<	2043:2043	arg1	r					2030:2030	r	2030:2030	r = 0.952	2030:2038	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	12	6	theme	<	2043:2043	arg1	p					2041:2041	p < 0.01	2041:2048	p < 0.01	2041:2048	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	13	7	theme	death	2273:2277	arg1	modes					2279:2283	bacterial cell death modes	2258:2283	bacterial cell death modes	2258:2283	Thus, in response to TiO2-NPs, bacterial cell death modes differentially weakened sludge dewatering.
30888807	0	8	theme	Sludge	119:124	arg1	Dewaterability					126:139	Sludge Dewaterability	119:139	Sludge Dewaterability	119:139	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	11	9	with	correlation	1656:1666	arg1	EPS					1723:1725	EPS	1723:1725	EPS	1723:1725	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	9	with	correlation	1656:1666	arg1	r					1769:1769	r = 0.974	1769:1777	r = 0.974	1769:1777	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	9	with	correlation	1656:1666	arg1	substances					1711:1720	extracellular polymeric substances	1687:1720	extracellular polymeric substances (EPS)	1687:1726	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	9	with	correlation	1656:1666	arg1	byproducts					1756:1765	total soluble microbial byproducts	1732:1765	total soluble microbial byproducts ( r = 0.974, p < 0.01)	1732:1788	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	9	10	theme	P25	1395:1397	arg1	NPs					1411:1413	P25 and anatase NPs	1395:1413	P25 and anatase NPs	1395:1413	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	2	11	theme	death	542:546	arg1	modes					548:552	sludge dewatering and bacterial cell death modes	505:552	sludge dewatering and bacterial cell death modes	505:552	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	9	12	theme	anatase	1403:1409	arg1	NPs					1411:1413	P25 and anatase NPs	1395:1413	P25 and anatase NPs	1395:1413	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	0	13	from	Sludge	62:67	arg1	Toxicity					0:7	Toxicity	0:7	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	0:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	12	14	theme	BW	2017:2018	arg1	content					2020:2026	BW content	2017:2026	BW content ( r = 0.952, p < 0.01)	2017:2049	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	10	15	theme	sludge	1563:1568	arg1	dewaterability					1570:1583	activated sludge dewaterability	1553:1583	activated sludge dewaterability	1553:1583	TiO2-NPs-sun reduced activated sludge dewaterability.
30888807	7	16	theme	crystalline	1028:1038	arg1	phases					1040:1045	crystalline phases	1028:1045	crystalline phases	1028:1045	The responses of bacterial communities to crystalline phases were more obvious than that of dosage.
30888807	11	17	theme	protein	1907:1913	arg1	concentrations					1915:1928	sludge protein concentrations	1900:1928	sludge protein concentrations	1900:1928	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	7	18	theme	communities	1013:1023	arg1	obvious					1057:1063	obvious	1057:1063	obvious	1057:1063	The responses of bacterial communities to crystalline phases were more obvious than that of dosage.
30888807	7	18	theme	communities	1013:1023	arg1	responses					990:998	The responses	986:998	The responses of bacterial communities to crystalline phases	986:1045	The responses of bacterial communities to crystalline phases were more obvious than that of dosage.
30888807	12	19	theme	high	2190:2193	arg1	protein					2195:2201	high protein and EPS concentrations	2190:2224	protein	2195:2201	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	11	20	theme	increased	1861:1869	arg1	content					1888:1894	especially the increased bound water (BW) content	1846:1894	especially the increased bound water (BW) content	1846:1894	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	12	21	theme	early	1991:1995	arg1	cells					2007:2011	early apoptotic cells	1991:2011	early apoptotic cells	1991:2011	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	9	22	theme	polysaccharide	1438:1451	arg1	affinities					1453:1462	higher protein and polysaccharide affinities	1419:1462	affinities	1453:1462	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	8	23	theme	intracellular	1304:1316	arg1	production					1322:1331	intracellular ROS production	1304:1331	intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control	1304:1392	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	11	24	theme	soluble	1738:1744	arg1	r					1769:1769	r = 0.974	1769:1777	r = 0.974	1769:1777	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	24	theme	soluble	1738:1744	arg1	byproducts					1756:1765	total soluble microbial byproducts	1732:1765	total soluble microbial byproducts ( r = 0.974, p < 0.01)	1732:1788	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	0	25	theme	Bacterial	70:78	arg1	Modes					91:95	Bacterial Cell Death Modes	70:95	Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	12:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	11	26	dep	r	1769:1769	arg1	p					1780:1780	p < 0.01	1780:1787	p < 0.01	1780:1787	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	1	27	theme	crystalline	174:184	arg1	phases					186:191	different crystalline phases	164:191	different crystalline phases of TiO2-NPs	164:203	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	2	28	theme	bacterial	527:535	arg1	death					542:546	bacterial cell death	527:546	bacterial cell death	527:546	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	0	29	from	Toxicity	0:7	arg1	Sludge					62:67	Activated Sludge	52:67	Activated Sludge	52:67	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	4	30	theme	scanning	770:777	arg1	microscopy					779:788	confocal laser scanning microscopy	755:788	confocal laser scanning microscopy	755:788	Bacterial survival and death were observed by confocal laser scanning microscopy.
30888807	0	31	theme	Death	85:89	arg1	Modes					91:95	Bacterial Cell Death Modes	70:95	Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	12:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	9	32	theme	rutile	1471:1476	arg1	NPs					1478:1480	rutile NPs	1471:1480	rutile NPs	1471:1480	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	2	33	theme	dewatering	512:521	arg1	modes					548:552	sludge dewatering and bacterial cell death modes	505:552	sludge dewatering and bacterial cell death modes	505:552	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	0	34	theme	Nanoparticles	35:47	arg1	Toxicity					0:7	Toxicity	0:7	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	0:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	2	35	theme	rutile	368:373	arg1	TiO2-NPs					375:382	rutile TiO2-NPs	368:382	rutile TiO2-NPs	368:382	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	5	36	theme	lactate	818:824	arg1	LDH					841:843	LDH	841:843	LDH	841:843	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	5	36	theme	lactate	818:824	arg1	dehydrogenase					826:838	lactate dehydrogenase	818:838	lactate dehydrogenase (LDH)	818:844	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	12	37	dep	content	2020:2026	arg1	r					2030:2030	r	2030:2030	r = 0.952	2030:2038	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	12	37	dep	content	2020:2026	arg1	p					2041:2041	p < 0.01	2041:2048	p < 0.01	2041:2048	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	4	38	theme	confocal	755:762	arg1	microscopy					779:788	confocal laser scanning microscopy	755:788	confocal laser scanning microscopy	755:788	Bacterial survival and death were observed by confocal laser scanning microscopy.
30888807	2	39	theme	flow	410:413	arg1	cytometry					415:423	flow cytometry	410:423	flow cytometry	410:423	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	9	40	contain	had	1415:1417	arg1	NPs					1411:1413	P25 and anatase NPs	1395:1413	P25 and anatase NPs	1395:1413	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	9	40	contain	had	1415:1417	arg2	affinities					1453:1462	higher protein and polysaccharide affinities	1419:1462	affinities	1453:1462	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	9	40	contain	had	1415:1417	arg2	protein					1426:1432	higher protein and polysaccharide affinities	1419:1462	protein	1426:1432	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	3	41	theme	community	645:653	arg1	structure					655:663	the microbial community structure	631:663	the microbial community structure	631:663	Additionally, the response of the microbial community structure was examined by high throughput sequencing.
30888807	1	42	theme	phases	186:191	arg1	controversial					209:221	controversial	209:221	controversial	209:221	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	1	42	theme	phases	186:191	arg1	eco-toxicities					146:159	The eco-toxicities	142:159	The eco-toxicities of different crystalline phases of TiO2-NPs	142:203	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	0	43	theme	TiO2	30:33	arg1	Nanoparticles					35:47	Three Crystalline TiO2 Nanoparticles	12:47	Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	12:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	11	44	theme	positive	1647:1654	arg1	correlation					1656:1666	the strongest positive correlation	1633:1666	the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01)	1633:1788	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	8	45	theme	necrosis-like	1117:1129	arg1	death					1136:1140	necrosis-like cell death	1117:1140	necrosis-like cell death	1117:1140	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	13	46	theme	bacterial	2258:2266	arg1	modes					2279:2283	bacterial cell death modes	2258:2283	bacterial cell death modes	2258:2283	Thus, in response to TiO2-NPs, bacterial cell death modes differentially weakened sludge dewatering.
30888807	11	47	theme	polymeric	1701:1709	arg1	EPS					1723:1725	EPS	1723:1725	EPS	1723:1725	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	47	theme	polymeric	1701:1709	arg1	substances					1711:1720	extracellular polymeric substances	1687:1720	extracellular polymeric substances (EPS)	1687:1726	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	8	48	theme	strong	1146:1151	arg1	photo-oxidation					1153:1167	strong photo-oxidation	1146:1167	strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control	1146:1392	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	12	49	dep	SRF	2148:2150	arg1	r					2154:2154	r	2154:2154	r = 0.959	2154:2162	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	12	49	dep	SRF	2148:2150	arg1	p					2165:2165	p < 0.01	2165:2172	p < 0.01	2165:2172	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	11	50	theme	bound	1681:1685	arg1	EPS					1723:1725	EPS	1723:1725	EPS	1723:1725	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	50	theme	bound	1681:1685	arg1	substances					1711:1720	extracellular polymeric substances	1687:1720	extracellular polymeric substances (EPS)	1687:1726	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	51	theme	Specific	1586:1593	arg1	resistance					1595:1604	Specific resistance	1586:1604	Specific resistance to filtration (SRF)	1586:1624	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	12	52	theme	correlation	1944:1954	arg1	coefficients					1956:1967	High Pearson correlation coefficients	1931:1967	High Pearson correlation coefficients	1931:1967	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	6	53	theme	TiO2-NPs	907:914	arg1	toxicity					916:923	TiO2-NPs toxicity	907:923	TiO2-NPs toxicity	907:923	Overall, TiO2-NPs toxicity was concentration-dependent and crystalline-phase-dependent.
30888807	1	54	theme	activated	258:266	arg1	sludge					268:273	activated sludge	258:273	activated sludge	258:273	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	3	55	theme	throughput	686:695	arg1	sequencing					697:706	high throughput sequencing	681:706	high throughput sequencing	681:706	Additionally, the response of the microbial community structure was examined by high throughput sequencing.
30888807	5	56	theme	oxygen	859:864	arg1	species					866:872	reactive oxygen species	850:872	reactive oxygen species (ROS)	850:878	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	5	56	theme	oxygen	859:864	arg1	ROS					875:877	ROS	875:877	ROS	875:877	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	12	57	theme	High	1931:1934	arg1	coefficients					1956:1967	High Pearson correlation coefficients	1931:1967	High Pearson correlation coefficients	1931:1967	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	10	58	theme	activated	1553:1561	arg1	dewaterability					1570:1583	activated sludge dewaterability	1553:1583	activated sludge dewaterability	1553:1583	TiO2-NPs-sun reduced activated sludge dewaterability.
30888807	1	59	theme	TiO2-NPs	196:203	arg1	phases					186:191	different crystalline phases	164:191	different crystalline phases of TiO2-NPs	164:203	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	13	60	theme	cell	2268:2271	arg1	modes					2279:2283	bacterial cell death modes	2258:2283	bacterial cell death modes	2258:2283	Thus, in response to TiO2-NPs, bacterial cell death modes differentially weakened sludge dewatering.
30888807	11	61	theme	=	1771:1771	arg1	r					1769:1769	r = 0.974	1769:1777	r = 0.974	1769:1777	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	61	theme	=	1771:1771	arg1	byproducts					1756:1765	total soluble microbial byproducts	1732:1765	total soluble microbial byproducts ( r = 0.974, p < 0.01)	1732:1788	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	12	62	theme	EPS	2207:2209	arg1	concentrations					2211:2224	high protein and EPS concentrations	2190:2224	concentrations	2211:2224	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	12	63	dep	cells	2138:2142	arg1	including					2112:2120	including	2112:2120	including late apoptotic	2112:2135	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	13	64	theme	sludge	2309:2314	arg1	dewatering					2316:2325	sludge dewatering	2309:2325	sludge dewatering	2309:2325	Thus, in response to TiO2-NPs, bacterial cell death modes differentially weakened sludge dewatering.
30888807	11	65	theme	BW	1884:1885	arg1	content					1888:1894	especially the increased bound water (BW) content	1846:1894	especially the increased bound water (BW) content	1846:1894	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	13	66	dep	TiO2-NPs	2248:2255	arg1	response					2236:2243	response	2236:2243	response	2236:2243	Thus, in response to TiO2-NPs, bacterial cell death modes differentially weakened sludge dewatering.
30888807	8	67	theme	%	1208:1208	arg1	%					1213:1213	301%/254%	1205:1213	301%/254% (50 mg/L)	1205:1223	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	8	67	theme	%	1208:1208	arg1	mg/L					1219:1222	50 mg/L	1216:1222	50 mg/L	1216:1222	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	2	68	theme	cell	537:540	arg1	death					542:546	bacterial cell death	527:546	bacterial cell death	527:546	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	8	69	theme	control	1386:1392	arg1	%					1349:1349	165%	1346:1349	165% (1 mg/L)	1346:1358	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	8	69	theme	control	1386:1392	arg1	mg/L					1354:1357	1 mg/L	1352:1357	1 mg/L	1352:1357	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	8	69	theme	control	1386:1392	arg1	control					1386:1392	the control	1382:1392	the control	1382:1392	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	8	69	theme	control	1386:1392	arg1	%					1367:1367	420%	1364:1367	420% (50 mg/L)	1364:1377	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	8	69	theme	control	1386:1392	arg1	mg/L					1373:1376	50 mg/L	1370:1376	50 mg/L	1370:1376	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	11	70	theme	<	1782:1782	arg1	p					1780:1780	p < 0.01	1780:1787	p < 0.01	1780:1787	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	1	71	from	mechanisms	244:253	arg1	sludge					268:273	activated sludge	258:273	activated sludge	258:273	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	11	72	theme	water	1877:1881	arg1	content					1888:1894	especially the increased bound water (BW) content	1846:1894	especially the increased bound water (BW) content	1846:1894	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	2	73	theme	correlation	570:580	arg1	r					597:597	r	597:597	r	597:597	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	2	73	theme	correlation	570:580	arg1	coefficients					582:593	Pearson's correlation coefficients	560:593	Pearson's correlation coefficients ( r)	560:598	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	4	74	theme	Bacterial	709:717	arg1	survival					719:726	Bacterial survival	709:726	Bacterial survival	709:726	Bacterial survival and death were observed by confocal laser scanning microscopy.
30888807	1	75	from	effects	232:238	arg1	sludge					268:273	activated sludge	258:273	activated sludge	258:273	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	11	76	theme	sludge	1900:1905	arg1	concentrations					1915:1928	sludge protein concentrations	1900:1928	sludge protein concentrations	1900:1928	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	9	77	theme	higher	1419:1424	arg1	protein					1426:1432	higher protein and polysaccharide affinities	1419:1462	protein	1426:1432	P25 and anatase NPs had higher protein and polysaccharide affinities, while rutile NPs exhibited stronger attachment onto phospholipids.
30888807	12	78	theme	<	2167:2167	arg1	r					2154:2154	r	2154:2154	r = 0.959	2154:2162	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	12	78	theme	<	2167:2167	arg1	p					2165:2165	p < 0.01	2165:2172	p < 0.01	2165:2172	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	8	79	theme	apoptosis-like	1279:1292	arg1	death					1294:1298	apoptosis-like death	1279:1298	apoptosis-like death	1279:1298	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	0	80	theme	Cell	80:83	arg1	Modes					91:95	Bacterial Cell Death Modes	70:95	Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	12:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	7	81	theme	bacterial	1003:1011	arg1	communities					1013:1023	bacterial communities	1003:1023	bacterial communities	1003:1023	The responses of bacterial communities to crystalline phases were more obvious than that of dosage.
30888807	1	82	theme	different	164:172	arg1	phases					186:191	different crystalline phases	164:191	different crystalline phases of TiO2-NPs	164:203	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	12	83	theme	apoptotic	1997:2005	arg1	cells					2007:2011	early apoptotic cells	1991:2011	early apoptotic cells	1991:2011	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	11	84	theme	microbial	1746:1754	arg1	r					1769:1769	r = 0.974	1769:1777	r = 0.974	1769:1777	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	84	theme	microbial	1746:1754	arg1	byproducts					1756:1765	total soluble microbial byproducts	1732:1765	total soluble microbial byproducts ( r = 0.974, p < 0.01)	1732:1788	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	2	85	from	acute-toxicities	315:330	arg1	sludge					397:402	activated sludge	387:402	activated sludge	387:402	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	4	86	theme	laser	764:768	arg1	microscopy					779:788	confocal laser scanning microscopy	755:788	confocal laser scanning microscopy	755:788	Bacterial survival and death were observed by confocal laser scanning microscopy.
30888807	8	87	theme	ROS	1318:1320	arg1	production					1322:1331	intracellular ROS production	1304:1331	intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control	1304:1392	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	11	88	theme	total	1732:1736	arg1	r					1769:1769	r = 0.974	1769:1777	r = 0.974	1769:1777	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	88	theme	total	1732:1736	arg1	byproducts					1756:1765	total soluble microbial byproducts	1732:1765	total soluble microbial byproducts ( r = 0.974, p < 0.01)	1732:1788	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	2	89	theme	sludge	505:510	arg1	dewatering					512:521	sludge dewatering	505:521	sludge dewatering	505:521	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	0	90	from	Nanoparticles	35:47	arg1	Sludge					62:67	Activated Sludge	52:67	Activated Sludge	52:67	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	2	91	theme	TiO2-NPs	375:382	arg1	acute-toxicities					315:330	the acute-toxicities	311:330	the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge	311:402	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	2	91	theme	TiO2-NPs	375:382	arg1	exposure					337:344	8-h exposure	333:344	8-h exposure	333:344	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	8	92	dep	LDH	1225:1227	arg1	released					1229:1236	released	1229:1236	released	1229:1236	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	2	93	theme	simulated	431:439	arg1	hereafter-sun					451:463	hereafter-sun	451:463	hereafter-sun	451:463	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	2	93	theme	simulated	431:439	arg1	sunlight					441:448	simulated sunlight	431:448	simulated sunlight (hereafter-sun)	431:464	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	0	94	theme	Crystalline	18:28	arg1	Nanoparticles					35:47	Three Crystalline TiO2 Nanoparticles	12:47	Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	12:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	3	95	theme	microbial	635:643	arg1	structure					655:663	the microbial community structure	631:663	the microbial community structure	631:663	Additionally, the response of the microbial community structure was examined by high throughput sequencing.
30888807	11	96	theme	bound	1871:1875	arg1	content					1888:1894	especially the increased bound water (BW) content	1846:1894	especially the increased bound water (BW) content	1846:1894	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	5	97	theme	Toxicity	791:798	arg1	indicators					800:809	Toxicity indicators	791:809	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS))	791:879	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	8	98	theme	cell	1131:1134	arg1	death					1136:1140	necrosis-like cell death	1117:1140	necrosis-like cell death	1117:1140	P25-sun and anatase-sun caused necrosis-like cell death via strong photo-oxidation confirmed by 131%/123% (1 mg/L) and 301%/254% (50 mg/L) LDH released by the control, while rutile-sun induced apoptosis-like death via intracellular ROS production increased to 165% (1 mg/L) and 420% (50 mg/L) of the control.
30888807	11	99	theme	strongest	1637:1645	arg1	correlation					1656:1666	the strongest positive correlation	1633:1666	the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01)	1633:1788	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	2	100	theme	activated	387:395	arg1	sludge					397:402	activated sludge	387:402	activated sludge	387:402	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	0	101	theme	Activated	52:60	arg1	Sludge					62:67	Activated Sludge	52:67	Activated Sludge	52:67	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	0	102	dep	Nanoparticles	35:47	arg1	Modes					91:95	Bacterial Cell Death Modes	70:95	Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes	12:95	Toxicity of Three Crystalline TiO2 Nanoparticles in Activated Sludge: Bacterial Cell Death Modes Differentially Weaken Sludge Dewaterability.
30888807	2	103	theme	anatase	355:361	arg1	acute-toxicities					315:330	the acute-toxicities	311:330	the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge	311:402	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	2	103	theme	anatase	355:361	arg1	exposure					337:344	8-h exposure	333:344	8-h exposure	333:344	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	11	104	theme	extracellular	1687:1699	arg1	EPS					1723:1725	EPS	1723:1725	EPS	1723:1725	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	11	104	theme	extracellular	1687:1699	arg1	substances					1711:1720	extracellular polymeric substances	1687:1720	extracellular polymeric substances (EPS)	1687:1726	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30888807	12	105	theme	necrotic	2102:2109	arg1	cells					2138:2142	necrotic (including late apoptotic) cells	2102:2142	necrotic (including late apoptotic) cells	2102:2142	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	1	106	dep	effects	232:238	arg1	the					228:230	the	228:230	the	228:230	The eco-toxicities of different crystalline phases of TiO2-NPs are controversial, and the effects and mechanisms on activated sludge are unclear.
30888807	3	107	theme	structure	655:663	arg1	response					619:626	the response	615:626	the response of the microbial community structure	615:663	Additionally, the response of the microbial community structure was examined by high throughput sequencing.
30888807	2	108	theme	8-h	333:335	arg1	acute-toxicities					315:330	the acute-toxicities	311:330	the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge	311:402	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	2	108	theme	8-h	333:335	arg1	exposure					337:344	8-h exposure	333:344	8-h exposure	333:344	Therefore, we assessed the acute-toxicities (8-h exposure) of P25, anatase, and rutile TiO2-NPs in activated sludge using flow cytometry under simulated sunlight (hereafter-sun) and evaluated the relationship between sludge dewatering and bacterial cell death modes using Pearson's correlation coefficients ( r).
30888807	5	109	theme	reactive	850:857	arg1	species					866:872	reactive oxygen species	850:872	reactive oxygen species (ROS)	850:878	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	5	109	theme	reactive	850:857	arg1	ROS					875:877	ROS	875:877	ROS	875:877	Toxicity indicators (e.g., lactate dehydrogenase (LDH) and reactive oxygen species (ROS)) were determined.
30888807	12	110	theme	massive	2066:2072	arg1	polysaccharides					2074:2088	massive polysaccharides	2066:2088	massive polysaccharides	2066:2088	High Pearson correlation coefficients were observed between early apoptotic cells and BW content ( r = 0.952, p < 0.01) resulting from massive polysaccharides and between necrotic (including late apoptotic) cells and SRF ( r = 0.959, p < 0.01) resulting from high protein and EPS concentrations.
30888807	11	111	theme	EPS	1817:1819	arg1	content					1821:1827	EPS content	1817:1827	EPS content	1817:1827	Specific resistance to filtration (SRF) showed the strongest positive correlation with tightly bound extracellular polymeric substances (EPS) and total soluble microbial byproducts ( r = 0.974, p < 0.01) and was closely related to EPS content and composition, especially the increased bound water (BW) content and sludge protein concentrations.
30575499	3	0	theme	Strain	296:301	arg1	HZ-65T					303:308	Strain HZ-65T	296:308	Strain HZ-65T	296:308	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	1	1	attach	isolated	81:88	arg2	Opitutaceae					69:79	the family Opitutaceae	58:79	the family Opitutaceae isolated from hyporheic freshwater	58:114	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	1	1	attach	isolated	81:88	arg1	freshwater					105:114	hyporheic freshwater	95:114	hyporheic freshwater	95:114	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	11	2	theme	aquaticus	1557:1565	arg1	HZ-65T					1570:1575	HZ-65T	1570:1575	HZ-65T (KACC 19333T=NBRC 112907T)	1570:1602	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	11	2	theme	aquaticus	1557:1565	arg1	strain					1535:1540	The type strain	1526:1540	The type strain of Nibricoccus aquaticus	1526:1565	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	3	3	theme	0 	411:412	arg1	NaCl					389:392	0-0.5 % NaCl	381:392	0-0.5 % NaCl (w/v; optimum at 0 % NaCl)	381:419	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	3	theme	0 	411:412	arg1	NaCl					415:418	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	7	4	theme	major	985:989	arg1	profile					1003:1009	The major polar lipid profile	981:1009	The major polar lipid profile	981:1009	The major polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol.
30575499	11	5	theme	19333T=NBRC	1583:1593	arg1	HZ-65T					1570:1575	HZ-65T	1570:1575	HZ-65T (KACC 19333T=NBRC 112907T)	1570:1602	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	11	5	theme	19333T=NBRC	1583:1593	arg1	112907T					1595:1601	KACC 19333T=NBRC 112907T	1578:1601	KACC 19333T=NBRC 112907T	1578:1601	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	3	6	theme	%	413:413	arg1	NaCl					389:392	0-0.5 % NaCl	381:392	0-0.5 % NaCl (w/v; optimum at 0 % NaCl)	381:419	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	6	theme	%	413:413	arg1	NaCl					415:418	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	9	7	theme	genetic	1314:1320	arg1	properties					1340:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	5	8	theme	quinone	813:819	arg1	menaquinone-7					833:845	menaquinone-7	833:845	menaquinone-7	833:845	The DNA G+C content was 62.2 mol% and the quinone present was menaquinone-7.
30575499	5	8	theme	quinone	813:819	arg1	present					821:827	the quinone present	809:827	the quinone present	809:827	The DNA G+C content was 62.2 mol% and the quinone present was menaquinone-7.
30575499	4	9	theme	Opitutaceae-type	722:737	arg1	strains					739:745	other Opitutaceae-type strains	716:745	other Opitutaceae-type strains	716:745	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	6	10	theme	total	962:966	arg1	acids					974:978	the total fatty acids	958:978	the total fatty acids	958:978	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	5	11	theme	62.2 mol	795:802	arg1	G+C content					779:789	The DNA G+C content	771:789	The DNA G+C content	771:789	The DNA G+C content was 62.2 mol% and the quinone present was menaquinone-7.
30575499	5	11	theme	62.2 mol	795:802	arg1	%					803:803	62.2 mol%	795:803	62.2 mol%	795:803	The DNA G+C content was 62.2 mol% and the quinone present was menaquinone-7.
30575499	4	12	theme	strain	483:488	arg1	HZ-65T					490:495	strain HZ-65T	483:495	strain HZ-65T	483:495	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	12	theme	strain	483:488	arg1	member					502:507	a member	500:507	a member of family Opitutaceae	500:529	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	5	13	theme	DNA	775:777	arg1	G+C content					779:789	The DNA G+C content	771:789	The DNA G+C content	771:789	The DNA G+C content was 62.2 mol% and the quinone present was menaquinone-7.
30575499	5	13	theme	DNA	775:777	arg1	%					803:803	62.2 mol%	795:803	62.2 mol%	795:803	The DNA G+C content was 62.2 mol% and the quinone present was menaquinone-7.
30575499	9	14	theme	new	1410:1412	arg1	genus					1414:1418	a new genus	1408:1418	a new genus within the family Opitutaceae	1408:1448	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	4	15	theme	other	716:720	arg1	strains					739:745	other Opitutaceae-type strains	716:745	other Opitutaceae-type strains	716:745	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	3	16	from	NaCl	415:418	arg1	optimum					400:406	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	16	from	NaCl	415:418	arg1	%					413:413	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	16	from	NaCl	415:418	arg1	w/v					395:397	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	16	from	NaCl	415:418	arg1	at					408:409	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	16	from	NaCl	415:418	arg1	0 					411:412	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	9	17	theme	phylogenetic	1327:1338	arg1	properties					1340:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	2	18	theme	yellow-coloured	119:133	arg1	bacterium					201:209	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium	117:209	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium	117:209	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	9	19	theme	gen.	1492:1495	arg1	nov.					1497:1500	Nibricoccus aquaticus gen. nov.	1470:1500	the name Nibricoccus aquaticus gen. nov.	1461:1500	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	1	20	theme	new	45:47	arg1	genus					49:53	a new genus	43:53	a new genus of the family Opitutaceae isolated from hyporheic freshwater	43:114	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	1	20	theme	new	45:47	arg1	nov.					37:40	nov.	37:40	nov.	37:40	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	8	21	theme	genes	1158:1162	arg1	presence					1142:1149	the presence	1138:1149	the presence of 300 genes that are involved in carbohydrate-active enzymes, which indicates the metabolic potential to degrade polysaccharides	1138:1279	Analysis of the HZ-65T genome revealed the presence of 300 genes that are involved in carbohydrate-active enzymes, which indicates the metabolic potential to degrade polysaccharides.
30575499	2	22	theme	hyporheic	249:257	arg1	freshwater					259:268	hyporheic freshwater	249:268	hyporheic freshwater	249:268	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	4	23	dep	Cephaloticoccus	646:660	arg1	capnophilus					662:672	capnophilus	662:672	capnophilus	662:672	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	0	24	theme	aquaticus	12:20	arg1	sp					33:34	sp	33:34	sp	33:34	Nibricoccus aquaticus gen. nov., sp.
30575499	0	24	theme	aquaticus	12:20	arg1	nov.					27:30	Nibricoccus aquaticus gen. nov.	0:30	Nibricoccus aquaticus gen. nov.	0:30	Nibricoccus aquaticus gen. nov., sp.
30575499	4	25	theme	16S	457:459	arg1	gene					466:469	the 16S rRNA gene	453:469	the 16S rRNA gene	453:469	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	3	26	dep	optimum	360:366	arg1	pH					369:370	pH 7.0	369:374	pH 7.0	369:374	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	9	27	theme	novel	1391:1395	arg1	species					1397:1403	a novel species	1389:1403	a novel species	1389:1403	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	4	28	theme	Cephaloticoccus	602:616	arg1	CAG34T					625:630	Cephaloticoccus primus CAG34T	602:630	Cephaloticoccus primus CAG34T (93.0 %)	602:639	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	28	theme	Cephaloticoccus	602:616	arg1	%					638:638	93.0 %	633:638	93.0 %	633:638	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	0	29	theme	Nibricoccus	0:10	arg1	sp					33:34	sp	33:34	sp	33:34	Nibricoccus aquaticus gen. nov., sp.
30575499	0	29	theme	Nibricoccus	0:10	arg1	nov.					27:30	Nibricoccus aquaticus gen. nov.	0:30	Nibricoccus aquaticus gen. nov.	0:30	Nibricoccus aquaticus gen. nov., sp.
30575499	4	30	dep	Cephaloticoccus	602:616	arg1	primus					618:623	primus	618:623	primus	618:623	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	2	31	theme	Korea	289:293	arg1	Republic					277:284	the Republic	273:284	the Republic of Korea	273:293	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	8	32	theme	HZ-65T	1115:1120	arg1	genome					1122:1127	the HZ-65T genome	1111:1127	the HZ-65T genome	1111:1127	Analysis of the HZ-65T genome revealed the presence of 300 genes that are involved in carbohydrate-active enzymes, which indicates the metabolic potential to degrade polysaccharides.
30575499	9	33	dep	name	1465:1468	arg1	nov.					1497:1500	Nibricoccus aquaticus gen. nov.	1470:1500	the name Nibricoccus aquaticus gen. nov.	1461:1500	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	4	34	theme	%	587:587	arg1	PB90-1T					573:579	Opitutus terrae PB90-1T	557:579	Opitutus terrae PB90-1T (94.0 % similarity)	557:599	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	34	theme	%	587:587	arg1	similarity					589:598	94.0 % similarity	582:598	94.0 % similarity	582:598	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	1	35	theme	family	62:67	arg1	Opitutaceae					69:79	the family Opitutaceae	58:79	the family Opitutaceae isolated from hyporheic freshwater	58:114	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	4	36	theme	family	512:517	arg1	Opitutaceae					519:529	family Opitutaceae	512:529	family Opitutaceae	512:529	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	0	37	theme	gen.	22:25	arg1	sp					33:34	sp	33:34	sp	33:34	Nibricoccus aquaticus gen. nov., sp.
30575499	0	37	theme	gen.	22:25	arg1	nov.					27:30	Nibricoccus aquaticus gen. nov.	0:30	Nibricoccus aquaticus gen. nov.	0:30	Nibricoccus aquaticus gen. nov., sp.
30575499	4	38	theme	rRNA	461:464	arg1	gene					466:469	the 16S rRNA gene	453:469	the 16S rRNA gene	453:469	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	1	39	theme	Opitutaceae	69:79	arg1	genus					49:53	a new genus	43:53	a new genus of the family Opitutaceae isolated from hyporheic freshwater	43:114	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	1	39	theme	Opitutaceae	69:79	arg1	nov.					37:40	nov.	37:40	nov.	37:40	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	9	40	theme	strain	1364:1369	arg1	HZ-65T					1371:1376	strain HZ-65T	1364:1376	strain HZ-65T	1364:1376	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	9	41	theme	Nibricoccus	1470:1480	arg1	nov.					1497:1500	Nibricoccus aquaticus gen. nov.	1470:1500	the name Nibricoccus aquaticus gen. nov.	1461:1500	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	2	42	dep	yellow-coloured	119:133	arg1	non-motile					158:167	non-motile	158:167	non-motile	158:167	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	2	42	dep	yellow-coloured	119:133	arg1	Gram-strain-negative					136:155	Gram-strain-negative	136:155	Gram-strain-negative	136:155	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	2	42	dep	yellow-coloured	119:133	arg1	cocci-shaped					170:181	cocci-shaped	170:181	cocci-shaped	170:181	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	2	42	dep	yellow-coloured	119:133	arg1	aerobic					193:199	aerobic	193:199	aerobic	193:199	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	9	43	theme	chemotaxonomic	1298:1311	arg1	properties					1340:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	3	44	theme	0-0.5 	381:386	arg1	%					387:387	%	387:387	%	387:387	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	9	45	dep	sp	1503:1504	arg1	name					1465:1468	the name	1461:1468	the name Nibricoccus aquaticus gen. nov.	1461:1500	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	4	46	theme	Phylogenetic	422:433	arg1	analysis					435:442	Phylogenetic analysis	422:442	Phylogenetic analysis based on the 16S rRNA gene	422:469	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	11	47	theme	KACC	1578:1581	arg1	HZ-65T					1570:1575	HZ-65T	1570:1575	HZ-65T (KACC 19333T=NBRC 112907T)	1570:1602	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	11	47	theme	KACC	1578:1581	arg1	112907T					1595:1601	KACC 19333T=NBRC 112907T	1578:1601	KACC 19333T=NBRC 112907T	1578:1601	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	3	48	theme	%	387:387	arg1	NaCl					415:418	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	48	theme	%	387:387	arg1	NaCl					389:392	0-0.5 % NaCl	381:392	0-0.5 % NaCl (w/v; optimum at 0 % NaCl)	381:419	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	49	theme	optimum	400:406	arg1	NaCl					389:392	0-0.5 % NaCl	381:392	0-0.5 % NaCl (w/v; optimum at 0 % NaCl)	381:419	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	49	theme	optimum	400:406	arg1	NaCl					415:418	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	9	50	theme	family	1431:1436	arg1	Opitutaceae					1438:1448	the family Opitutaceae	1427:1448	the family Opitutaceae	1427:1448	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	9	51	theme	aquaticus	1482:1490	arg1	nov.					1497:1500	Nibricoccus aquaticus gen. nov.	1470:1500	the name Nibricoccus aquaticus gen. nov.	1461:1500	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	3	52	theme	at	408:409	arg1	NaCl					389:392	0-0.5 % NaCl	381:392	0-0.5 % NaCl (w/v; optimum at 0 % NaCl)	381:419	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	52	theme	at	408:409	arg1	NaCl					415:418	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	6	53	theme	fatty	968:972	arg1	acids					974:978	the total fatty acids	958:978	the total fatty acids	958:978	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	3	54	dep	optimum	328:334	arg1	25-30 °C					337:344	25-30 °C	337:344	25-30 °C	337:344	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	11	55	theme	type	1530:1533	arg1	HZ-65T					1570:1575	HZ-65T	1570:1575	HZ-65T (KACC 19333T=NBRC 112907T)	1570:1602	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	11	55	theme	type	1530:1533	arg1	strain					1535:1540	The type strain	1526:1540	The type strain of Nibricoccus aquaticus	1526:1565	The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).
30575499	8	56	theme	metabolic	1234:1242	arg1	potential					1244:1252	the metabolic potential	1230:1252	the metabolic potential to degrade polysaccharides	1230:1279	Analysis of the HZ-65T genome revealed the presence of 300 genes that are involved in carbohydrate-active enzymes, which indicates the metabolic potential to degrade polysaccharides.
30575499	6	57	theme	fatty	864:868	arg1	iso-C14 					881:888	iso-C14 	881:888	iso-C14 	881:888	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	6	57	theme	fatty	864:868	arg1	acids					870:874	The predominant fatty acids	848:874	The predominant fatty acids	848:874	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	3	58	theme	w/v	395:397	arg1	NaCl					389:392	0-0.5 % NaCl	381:392	0-0.5 % NaCl (w/v; optimum at 0 % NaCl)	381:419	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	3	58	theme	w/v	395:397	arg1	NaCl					415:418	w/v; optimum at 0 % NaCl	395:418	w/v; optimum at 0 % NaCl	395:418	Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl).
30575499	8	59	theme	carbohydrate-active	1185:1203	arg1	enzymes					1205:1211	carbohydrate-active enzymes	1185:1211	carbohydrate-active enzymes	1185:1211	Analysis of the HZ-65T genome revealed the presence of 300 genes that are involved in carbohydrate-active enzymes, which indicates the metabolic potential to degrade polysaccharides.
30575499	2	60	attach	isolated	235:242	arg2	bacterium					201:209	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium	117:209	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium	117:209	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	2	60	attach	isolated	235:242	arg1	freshwater					259:268	hyporheic freshwater	249:268	hyporheic freshwater	249:268	A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea.
30575499	4	61	dep	Opitutus	557:564	arg1	terrae					566:571	terrae	566:571	terrae	566:571	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	6	62	dep	iso-C14 	881:888	arg1	 0					933:934	 0	933:934	 0	933:934	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	8	63	theme	genome	1122:1127	arg1	Analysis					1099:1106	Analysis	1099:1106	Analysis of the HZ-65T genome	1099:1127	Analysis of the HZ-65T genome revealed the presence of 300 genes that are involved in carbohydrate-active enzymes, which indicates the metabolic potential to degrade polysaccharides.
30575499	9	64	from	species	1397:1403	arg1	genus					1414:1418	a new genus	1408:1418	a new genus within the family Opitutaceae	1408:1448	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	1	65	theme	hyporheic	95:103	arg1	freshwater					105:114	hyporheic freshwater	95:114	hyporheic freshwater	95:114	nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.
30575499	7	66	theme	lipid	997:1001	arg1	profile					1003:1009	The major polar lipid profile	981:1009	The major polar lipid profile	981:1009	The major polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol.
30575499	4	67	theme	Opitutaceae	519:529	arg1	HZ-65T					490:495	strain HZ-65T	483:495	strain HZ-65T	483:495	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	67	theme	Opitutaceae	519:529	arg1	member					502:507	a member	500:507	a member of family Opitutaceae	500:529	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	6	68	theme	acids	974:978	arg1	acids					974:978	the total fatty acids	958:978	the total fatty acids	958:978	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	6	68	theme	acids	974:978	arg1	%					953:953	70 %	950:953	70 % of the total fatty acids	950:978	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	9	69	theme	phenotypic	1286:1295	arg1	properties					1340:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties	1282:1349	The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp.
30575499	6	70	theme	predominant	852:862	arg1	iso-C14 					881:888	iso-C14 	881:888	iso-C14 	881:888	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	6	70	theme	predominant	852:862	arg1	acids					870:874	The predominant fatty acids	848:874	The predominant fatty acids	848:874	The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids.
30575499	7	71	theme	polar	991:995	arg1	profile					1003:1009	The major polar lipid profile	981:1009	The major polar lipid profile	981:1009	The major polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol.
30575499	4	72	theme	Cephaloticoccus	646:660	arg1	CV41T					674:678	Cephaloticoccus capnophilus CV41T	646:678	Cephaloticoccus capnophilus CV41T (92.7 %)	646:687	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	72	theme	Cephaloticoccus	646:660	arg1	%					686:686	92.7 %	681:686	92.7 %	681:686	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	73	theme	Opitutus	557:564	arg1	PB90-1T					573:579	Opitutus terrae PB90-1T	557:579	Opitutus terrae PB90-1T (94.0 % similarity)	557:599	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	73	theme	Opitutus	557:564	arg1	similarity					589:598	94.0 % similarity	582:598	94.0 % similarity	582:598	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	74	theme	94.0 	582:586	arg1	PB90-1T					573:579	Opitutus terrae PB90-1T	557:579	Opitutus terrae PB90-1T (94.0 % similarity)	557:599	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30575499	4	74	theme	94.0 	582:586	arg1	similarity					589:598	94.0 % similarity	582:598	94.0 % similarity	582:598	Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %.
30007690	8	0	theme	Future	1269:1274	arg1	studies					1276:1282	Future studies	1269:1282	Future studies	1269:1282	Future studies should be done to determine the type of carbohydrates and the relationship between chitin - beta glucans responsible for mycotoxin adsorption.
30007690	3	1	theme	DDGse	762:766	arg1	medium					768:773	yeast extract peptone dextrose (YPD) or DDGse medium	722:773	medium	768:773	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	1	2	theme	dry	210:212	arg1	extract					239:245	dry distillery grain soluble extract	210:245	dry distillery grain soluble extract	210:245	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	4	3	theme	CW	839:840	arg1	thickness					822:830	The thickness	818:830	The thickness of the CW for S. cerevisiae (RC012 and VM014)	818:876	The thickness of the CW for S. cerevisiae (RC012 and VM014) were increased when the cells were grown in DDGse medium, the thickness was almost double compared to the values obtained in YPD medium.
30007690	1	4	theme	cell	294:297	arg1	CW					305:306	CW	305:306	CW	305:306	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	4	theme	cell	294:297	arg1	wall					299:302	cell wall	294:302	cell wall (CW)	294:307	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	3	5	theme	dextrose	744:751	arg1	YPD					754:756	yeast extract peptone dextrose (YPD) or DDGse medium	722:773	YPD	754:756	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	1	6	theme	distillery	214:223	arg1	extract					239:245	dry distillery grain soluble extract	210:245	dry distillery grain soluble extract	210:245	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	7	7	theme	whole	1257:1261	arg1	cell					1263:1266	whole cell	1257:1266	whole cell	1257:1266	The CW adsorbed more AFB1 than the same amount of whole cell.
30007690	4	8	dep	cerevisiae	849:858	arg1	VM014					871:875	VM014	871:875	VM014	871:875	The thickness of the CW for S. cerevisiae (RC012 and VM014) were increased when the cells were grown in DDGse medium, the thickness was almost double compared to the values obtained in YPD medium.
30007690	4	8	dep	cerevisiae	849:858	arg1	RC012					861:865	RC012	861:865	RC012	861:865	The thickness of the CW for S. cerevisiae (RC012 and VM014) were increased when the cells were grown in DDGse medium, the thickness was almost double compared to the values obtained in YPD medium.
30007690	1	9	theme	transmission	518:529	arg1	TEM					552:554	TEM	552:554	TEM	552:554	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	9	theme	transmission	518:529	arg1	microscopy					540:549	transmission electron microscopy	518:549	transmission electron microscopy (TEM)	518:555	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	10	theme	grain	225:229	arg1	extract					239:245	dry distillery grain soluble extract	210:245	dry distillery grain soluble extract	210:245	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	0	11	theme	wall	79:82	arg1	thickness					84:92	the wall thickness	75:92	the wall thickness	75:92	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	7	12	theme	same	1242:1245	arg1	amount					1247:1252	the same amount	1238:1252	the same amount of whole cell	1238:1266	The CW adsorbed more AFB1 than the same amount of whole cell.
30007690	7	12	theme	same	1242:1245	arg1	cell					1263:1266	whole cell	1257:1266	whole cell	1257:1266	The CW adsorbed more AFB1 than the same amount of whole cell.
30007690	1	13	theme	CW	424:425	arg1	thickness					407:415	thickness	407:415	thickness	407:415	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	13	theme	CW	424:425	arg1	composition					391:401	composition	391:401	composition	391:401	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	14	theme	soluble	231:237	arg1	extract					239:245	dry distillery grain soluble extract	210:245	dry distillery grain soluble extract	210:245	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	5	15	theme	culture	1052:1058	arg1	media					1060:1064	the two culture media	1044:1064	the two culture media	1044:1064	The spectra IR of each CW in the two culture media shown regions corresponding to polysaccharides, proteins and lipids.
30007690	1	16	dep	composition	391:401	arg1	the					387:389	the	387:389	the	387:389	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	3	17	theme	S.	693:694	arg1	strain					706:711	that S. boulardii strain	688:711	that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium	688:773	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	6	18	theme	DDGse	1150:1154	arg1	medium					1156:1161	DDGse medium	1150:1161	DDGse medium	1150:1161	Cells grown in DDGse medium adsorbed more AFB1 than those grown in YPD.
30007690	8	19	theme	mycotoxin	1405:1413	arg1	adsorption					1415:1424	mycotoxin adsorption	1405:1424	mycotoxin adsorption	1405:1424	Future studies should be done to determine the type of carbohydrates and the relationship between chitin - beta glucans responsible for mycotoxin adsorption.
30007690	1	20	theme	electron	531:538	arg1	TEM					552:554	TEM	552:554	TEM	552:554	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	20	theme	electron	531:538	arg1	microscopy					540:549	transmission electron microscopy	518:549	transmission electron microscopy (TEM)	518:555	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	8	21	theme	carbohydrates	1324:1336	arg1	relationship					1346:1357	the relationship	1342:1357	the relationship between chitin - beta glucans responsible for mycotoxin adsorption	1342:1424	Future studies should be done to determine the type of carbohydrates and the relationship between chitin - beta glucans responsible for mycotoxin adsorption.
30007690	8	21	theme	carbohydrates	1324:1336	arg1	type					1316:1319	the type	1312:1319	the type of carbohydrates	1312:1336	Future studies should be done to determine the type of carbohydrates and the relationship between chitin - beta glucans responsible for mycotoxin adsorption.
30007690	2	22	theme	biomass	627:633	arg1	production					613:622	The production	609:622	The production of biomass and CW	609:640	The production of biomass and CW were variable.
30007690	2	22	theme	biomass	627:633	arg1	variable					647:654	variable	647:654	variable	647:654	The production of biomass and CW were variable.
30007690	1	23	theme	extract	239:245	arg1	use					203:205	the use	199:205	the use of dry distillery grain soluble extract	199:245	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	3	24	theme	significant	784:794	arg1	differences					796:806	no significant differences	781:806	no significant differences observed	781:815	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	0	25	theme	yeast	18:22	arg1	wall					29:32	yeast cell wall	18:32	yeast cell wall using an agroindustrial waste	18:62	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	5	26	from	IR	1027:1028	arg1	media					1060:1064	the two culture media	1044:1064	the two culture media	1044:1064	The spectra IR of each CW in the two culture media shown regions corresponding to polysaccharides, proteins and lipids.
30007690	1	27	theme	DDGse	450:454	arg1	influence					437:445	the influence	433:445	the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR)	433:606	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	28	theme	study	175:179	arg1	evaluate					190:197	evaluate	190:197	to evaluate the use of dry distillery grain soluble extract	187:245	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	28	theme	study	175:179	arg1	objectives					156:165	The objectives	152:165	The objectives of this study	152:179	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	29	from	implication	474:484	arg1	process					504:510	the adsorption process	489:510	the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR)	489:606	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	0	30	theme	wall	29:32	arg1	production					4:13	The production	0:13	The production of yeast cell wall using an agroindustrial waste	0:62	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	2	31	theme	CW	639:640	arg1	production					613:622	The production	609:622	The production of biomass and CW	609:640	The production of biomass and CW were variable.
30007690	2	31	theme	CW	639:640	arg1	variable					647:654	variable	647:654	variable	647:654	The production of biomass and CW were variable.
30007690	0	32	theme	aflatoxin	119:127	arg1	B1					129:130	aflatoxin B1	119:130	the aflatoxin B1 adsorption process	115:149	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	1	33	from	variation	374:382	arg1	thickness					407:415	thickness	407:415	thickness	407:415	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	33	from	variation	374:382	arg1	composition					391:401	composition	391:401	composition	391:401	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	0	34	theme	cell	24:27	arg1	wall					29:32	yeast cell wall	18:32	yeast cell wall using an agroindustrial waste	18:62	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	5	35	theme	spectra	1019:1025	arg1	IR					1027:1028	The spectra IR	1015:1028	The spectra IR of each CW in the two culture media	1015:1064	The spectra IR of each CW in the two culture media shown regions corresponding to polysaccharides, proteins and lipids.
30007690	1	36	dep	evaluate	190:197	arg1	obtain					287:292	obtain	287:292	to obtain cell wall (CW)	284:307	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	36	dep	evaluate	190:197	arg1	produce					258:264	produce	258:264	to produce yeast biomass	255:278	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	8	37	theme	responsible	1389:1399	arg1	glucans					1381:1387	chitin - beta glucans	1367:1387	chitin - beta glucans responsible for mycotoxin adsorption	1367:1424	Future studies should be done to determine the type of carbohydrates and the relationship between chitin - beta glucans responsible for mycotoxin adsorption.
30007690	4	38	theme	YPD	1003:1005	arg1	medium					1007:1012	YPD medium	1003:1012	YPD medium	1003:1012	The thickness of the CW for S. cerevisiae (RC012 and VM014) were increased when the cells were grown in DDGse medium, the thickness was almost double compared to the values obtained in YPD medium.
30007690	1	39	theme	fourier-transform	561:577	arg1	FITR					602:605	FITR	602:605	FITR	602:605	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	39	theme	fourier-transform	561:577	arg1	spectroscopy					588:599	fourier-transform infrared spectroscopy	561:599	fourier-transform infrared spectroscopy (FITR)	561:606	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	40	theme	yeast	266:270	arg1	biomass					272:278	yeast biomass	266:278	yeast biomass	266:278	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	0	41	theme	adsorption	132:141	arg1	process					143:149	the aflatoxin B1 adsorption process	115:149	the aflatoxin B1 adsorption process	115:149	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	1	42	theme	infrared	579:586	arg1	FITR					602:605	FITR	602:605	FITR	602:605	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	42	theme	infrared	579:586	arg1	spectroscopy					588:599	fourier-transform infrared spectroscopy	561:599	fourier-transform infrared spectroscopy (FITR)	561:606	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	8	43	theme	chitin	1367:1372	arg1	glucans					1381:1387	chitin - beta glucans	1367:1387	chitin - beta glucans responsible for mycotoxin adsorption	1367:1424	Future studies should be done to determine the type of carbohydrates and the relationship between chitin - beta glucans responsible for mycotoxin adsorption.
30007690	0	44	theme	B1	129:130	arg1	process					143:149	the aflatoxin B1 adsorption process	115:149	the aflatoxin B1 adsorption process	115:149	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	3	45	dep	S.	693:694	arg1	boulardii					696:704	boulardii	696:704	boulardii	696:704	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	3	46	theme	extract	728:734	arg1	YPD					754:756	yeast extract peptone dextrose (YPD) or DDGse medium	722:773	YPD	754:756	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	3	47	theme	peptone	736:742	arg1	YPD					754:756	yeast extract peptone dextrose (YPD) or DDGse medium	722:773	YPD	754:756	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	8	48	theme	beta	1376:1379	arg1	glucans					1381:1387	chitin - beta glucans	1367:1387	chitin - beta glucans responsible for mycotoxin adsorption	1367:1424	Future studies should be done to determine the type of carbohydrates and the relationship between chitin - beta glucans responsible for mycotoxin adsorption.
30007690	1	49	theme	aflatoxin	330:338	arg1	AFB1					344:347	AFB1	344:347	AFB1	344:347	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	1	49	theme	aflatoxin	330:338	arg1	B1					340:341	an aflatoxin B1	327:341	an aflatoxin B1 (AFB1)	327:348	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	7	50	dep	AFB1	1228:1231	arg1	more					1223:1226	more	1223:1226	more	1223:1226	The CW adsorbed more AFB1 than the same amount of whole cell.
30007690	4	51	theme	DDGse	922:926	arg1	medium					928:933	DDGse medium	922:933	DDGse medium	922:933	The thickness of the CW for S. cerevisiae (RC012 and VM014) were increased when the cells were grown in DDGse medium, the thickness was almost double compared to the values obtained in YPD medium.
30007690	5	52	theme	CW	1038:1039	arg1	IR					1027:1028	The spectra IR	1015:1028	The spectra IR of each CW in the two culture media	1015:1064	The spectra IR of each CW in the two culture media shown regions corresponding to polysaccharides, proteins and lipids.
30007690	3	53	theme	yeast	722:726	arg1	YPD					754:756	yeast extract peptone dextrose (YPD) or DDGse medium	722:773	YPD	754:756	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	3	54	theme	thickness	664:672	arg1	values					674:679	The CW thickness values	657:679	The CW thickness values	657:679	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
30007690	0	55	theme	agroindustrial	43:56	arg1	waste					58:62	an agroindustrial waste	40:62	an agroindustrial waste	40:62	The production of yeast cell wall using an agroindustrial waste influences the wall thickness and is implicated on the aflatoxin B1 adsorption process.
30007690	7	56	theme	cell	1263:1266	arg1	amount					1247:1252	the same amount	1238:1252	the same amount of whole cell	1238:1266	The CW adsorbed more AFB1 than the same amount of whole cell.
30007690	7	56	theme	cell	1263:1266	arg1	cell					1263:1266	whole cell	1257:1266	whole cell	1257:1266	The CW adsorbed more AFB1 than the same amount of whole cell.
30007690	1	57	theme	adsorption	493:502	arg1	process					504:510	the adsorption process	489:510	the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR)	489:606	The objectives of this study were: to evaluate the use of dry distillery grain soluble extract - DDGse to produce yeast biomass and to obtain cell wall (CW), to use the CW as an aflatoxin B1 (AFB1) adsorbent, to study the variation in the composition and thickness of the CW under the influence of DDGse to evaluate their implication on the adsorption process using transmission electron microscopy (TEM) and fourier-transform infrared spectroscopy (FITR).
30007690	3	58	theme	CW	661:662	arg1	values					674:679	The CW thickness values	657:679	The CW thickness values	657:679	The CW thickness values showed that S. boulardii strain grown in yeast extract peptone dextrose (YPD) or DDGse medium, with no significant differences observed.
31847093	6	0	theme	disordered	881:890	arg1	regions					892:898	disordered regions	881:898	disordered regions within the most conserved cluster	881:932	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	7	1	theme	O-linked	1135:1142	arg1	glycans					1144:1150	O-linked glycans	1135:1150	O-linked glycans	1135:1150	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	2	2	theme	metabolism	308:317	arg1	understanding					284:296	the understanding	280:296	the understanding of glycan metabolism and function	280:330	Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function.
31847093	6	3	theme	disordered	955:964	arg1	regions					966:972	disordered regions	955:972	disordered regions	955:972	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	6	4	theme	significant	856:866	arg1	abundance					868:876	The significant abundance	852:876	The significant abundance of disordered regions within the most conserved cluster	852:932	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	7	5	theme	N-	1128:1129	arg1	acquisition					1113:1123	the acquisition	1109:1123	the acquisition of N- and O-linked glycans	1109:1150	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	2	6	theme	glycan	301:306	arg1	metabolism					308:317	glycan metabolism	301:317	glycan metabolism	301:317	Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function.
31847093	7	7	theme	multicellular	1071:1083	arg1	organisms					1085:1093	multicellular organisms	1071:1093	multicellular organisms	1071:1093	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	3	8	theme	hydrolases	447:456	arg1	analysis					413:420	a genome-wide analysis	399:420	a genome-wide analysis of whole human glycoside hydrolases	399:456	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	1	9	theme	glycosyltransferases	165:184	arg1	functions					152:160	the functions	148:160	the functions of glycosyltransferases and glycoside hydrolases	148:209	Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases.
31847093	3	10	theme	glycosyltransferases	364:383	arg1	study					355:359	our previous study	342:359	our previous study of glycosyltransferases	342:383	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	3	11	theme	human	431:435	arg1	hydrolases					447:456	whole human glycoside hydrolases	425:456	whole human glycoside hydrolases	425:456	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	5	12	theme	O-glycoside	814:824	arg1	hydrolases					826:835	O-glycoside hydrolases	814:835	O-glycoside hydrolases	814:835	The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively.
31847093	3	13	theme	genome-wide	401:411	arg1	analysis					413:420	a genome-wide analysis	399:420	a genome-wide analysis of whole human glycoside hydrolases	399:456	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	3	14	theme	whole	425:429	arg1	hydrolases					447:456	whole human glycoside hydrolases	425:456	whole human glycoside hydrolases	425:456	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	1	15	theme	glycoside	190:198	arg1	hydrolases					200:209	glycoside hydrolases	190:209	glycoside hydrolases	190:209	Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases.
31847093	0	16	theme	Genome-Wide	0:10	arg1	Analysis					12:19	Genome-Wide Analysis	0:19	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.	0:90	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.
31847093	1	17	theme	hydrolases	200:209	arg1	functions					152:160	the functions	148:160	the functions of glycosyltransferases and glycoside hydrolases	148:209	Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases.
31847093	0	18	theme	Whole	24:28	arg1	Hydrolases					46:55	Whole Human Glycoside Hydrolases	24:55	Whole Human Glycoside Hydrolases	24:55	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.
31847093	2	19	theme	function	323:330	arg1	understanding					284:296	the understanding	280:296	the understanding of glycan metabolism and function	280:330	Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function.
31847093	5	20	theme	metazoan	780:787	arg1	clusters					789:796	The eukaryote and metazoan clusters	762:796	The eukaryote and metazoan clusters	762:796	The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively.
31847093	7	21	theme	glycans	1144:1150	arg1	acquisition					1113:1123	the acquisition	1109:1123	the acquisition of N- and O-linked glycans	1109:1150	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	7	22	theme	biological	1047:1056	arg1	related					1098:1104	related	1098:1104	related	1098:1104	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	7	22	theme	biological	1047:1056	arg1	diversity					1058:1066	the biological diversity	1043:1066	the biological diversity of multicellular organisms	1043:1093	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	5	23	theme	eukaryote	766:774	arg1	clusters					789:796	The eukaryote and metazoan clusters	762:796	The eukaryote and metazoan clusters	762:796	The eukaryote and metazoan clusters included N- and O-glycoside hydrolases, respectively.
31847093	3	24	theme	CAZy	485:488	arg1	databases					499:507	the UniProt, BRENDA, CAZy and KEGG databases	464:507	the UniProt, BRENDA, CAZy and KEGG databases	464:507	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	0	25	theme	Glycoside	36:44	arg1	Hydrolases					46:55	Whole Human Glycoside Hydrolases	24:55	Whole Human Glycoside Hydrolases	24:55	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.
31847093	6	26	from	role	946:949	arg1	evolution					981:989	the evolution	977:989	the evolution of glycoside hydrolases	977:1013	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	0	27	theme	Human	30:34	arg1	Hydrolases					46:55	Whole Human Glycoside Hydrolases	24:55	Whole Human Glycoside Hydrolases	24:55	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.
31847093	4	28	theme	human	538:542	arg1	hydrolases					554:563	319 human glycoside hydrolases	534:563	319 human glycoside hydrolases	534:563	Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3) and eukaryotes (Class 4).
31847093	3	29	theme	glycoside	437:445	arg1	hydrolases					447:456	whole human glycoside hydrolases	425:456	whole human glycoside hydrolases	425:456	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	0	30	from	Analysis	72:79	arg1	Silico					84:89	Silico	84:89	Silico	84:89	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.
31847093	2	31	theme	enzymes	245:251	arg1	evolution					226:234	the evolution	222:234	the evolution of these enzymes	222:251	Analysing the evolution of these enzymes is essential for improving the understanding of glycan metabolism and function.
31847093	3	32	theme	BRENDA	477:482	arg1	databases					499:507	the UniProt, BRENDA, CAZy and KEGG databases	464:507	the UniProt, BRENDA, CAZy and KEGG databases	464:507	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	6	33	theme	conserved	916:924	arg1	cluster					926:932	the most conserved cluster	907:932	the most conserved cluster	907:932	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	0	34	theme	Hydrolases	46:55	arg1	Analysis					12:19	Genome-Wide Analysis	0:19	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.	0:90	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.
31847093	6	35	theme	regions	892:898	arg1	abundance					868:876	The significant abundance	852:876	The significant abundance of disordered regions within the most conserved cluster	852:932	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	7	36	theme	organisms	1085:1093	arg1	related					1098:1104	related	1098:1104	related	1098:1104	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	7	36	theme	organisms	1085:1093	arg1	diversity					1058:1066	the biological diversity	1043:1066	the biological diversity of multicellular organisms	1043:1093	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	1	37	theme	various	116:122	arg1	processes					134:142	various metabolic processes	116:142	various metabolic processes	116:142	Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases.
31847093	4	38	theme	glycoside	544:552	arg1	hydrolases					554:563	319 human glycoside hydrolases	534:563	319 human glycoside hydrolases	534:563	Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3) and eukaryotes (Class 4).
31847093	7	39	link	O-linked	1135:1142	arg1	glycans					1144:1150	O-linked glycans	1135:1150	O-linked glycans	1135:1150	These results suggest that the biological diversity of multicellular organisms is related to the acquisition of N- and O-linked glycans.
31847093	1	40	theme	metabolic	124:132	arg1	processes					134:142	various metabolic processes	116:142	various metabolic processes	116:142	Glycans are involved in various metabolic processes via the functions of glycosyltransferases and glycoside hydrolases.
31847093	6	41	theme	glycoside	994:1002	arg1	hydrolases					1004:1013	glycoside hydrolases	994:1013	glycoside hydrolases	994:1013	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	3	42	theme	KEGG	494:497	arg1	databases					499:507	the UniProt, BRENDA, CAZy and KEGG databases	464:507	the UniProt, BRENDA, CAZy and KEGG databases	464:507	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	3	43	theme	previous	346:353	arg1	study					355:359	our previous study	342:359	our previous study of glycosyltransferases	342:383	Based on our previous study of glycosyltransferases, we performed a genome-wide analysis of whole human glycoside hydrolases using the UniProt, BRENDA, CAZy and KEGG databases.
31847093	6	44	theme	hydrolases	1004:1013	arg1	evolution					981:989	the evolution	977:989	the evolution of glycoside hydrolases	977:1013	The significant abundance of disordered regions within the most conserved cluster indicated a role for disordered regions in the evolution of glycoside hydrolases.
31847093	0	45	theme	Data-Driven	60:70	arg1	Analysis					72:79	Data-Driven Analysis	60:79	Data-Driven Analysis in Silico	60:89	Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.
31847093	4	46	theme	cluster	516:522	arg1	analysis					524:531	cluster analysis	516:531	cluster analysis	516:531	Using cluster analysis, 319 human glycoside hydrolases were classified into four clusters based on their similarity to enzymes conserved in chordates or metazoans (Class 1), metazoans (Class 2), metazoans and plants (Class 3) and eukaryotes (Class 4).
31710461	4	0	from	differences	683:693	arg1	nature					702:707	the nature	698:707	the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry	698:801	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	5	1	theme	Asn	866:868	arg1	sites					870:874	partially glycosylated Asn sites	843:874	partially glycosylated Asn sites	843:874	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	4	2	from	ChyB	581:584	arg1	lysates					612:618	profiling lysates	602:618	profiling lysates	602:618	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	2	3	theme	expanded	388:395	arg1	preference					397:406	an expanded preference	385:406	an expanded preference for Asn-containing substrates	385:436	The engineered variant (chymotrypsiN, ChyB-Asn) demonstrated an altered substrate specificity with an expanded preference for Asn-containing substrates.
31710461	1	4	theme	pocket	278:283	arg1	remodeling					242:251	comprehensive remodeling	228:251	comprehensive remodeling of the substrate binding pocket	228:283	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	5	5	theme	sites	870:874	arg1	identification					825:838	the identification	821:838	the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells	821:954	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	4	6	theme	ChyB	581:584	arg1	Comparison					557:566	Comparison	557:566	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells	557:634	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	1	7	theme	high-throughput	172:186	arg1	screening					188:196	high-throughput screening	172:196	high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket	172:283	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	4	8	theme	wild-type	571:579	arg1	ChyB					581:584	wild-type ChyB	571:584	wild-type ChyB	571:584	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	5	9	gly	glycosylated	853:864	arg1	sites					870:874	partially glycosylated Asn sites	843:874	partially glycosylated Asn sites	843:874	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	4	10	from	Comparison	557:566	arg1	lysates					612:618	profiling lysates	602:618	profiling lysates	602:618	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	4	11	theme	tandem	778:783	arg1	spectrometry					790:801	tandem mass spectrometry	778:801	tandem mass spectrometry	778:801	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	3	12	theme	biophysical	527:537	arg1	characterization					539:554	biophysical characterization	527:554	biophysical characterization	527:554	We confirmed that protein engineering did not compromise the stability of the enzyme by biophysical characterization.
31710461	4	13	theme	proteins	729:736	arg1	nature					702:707	the nature	698:707	the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry	698:801	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	4	14	theme	qualitative	654:664	arg1	differences					683:693	both qualitative and quantitative differences	649:693	both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry	649:801	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	6	15	theme	valuable	975:982	arg1	addition					984:991	a valuable addition	973:991	a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes	973:1100	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	6	15	theme	valuable	975:982	arg1	ChymotrypsiN					957:968	ChymotrypsiN	957:968	ChymotrypsiN	957:968	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	6	16	gly	glycosylation	1052:1064	arg2	sites					1066:1070	N-linked glycosylation sites	1043:1070	N-linked glycosylation sites within proteins and proteomes	1043:1100	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	4	17	theme	HEK293	623:628	arg1	cells					630:634	HEK293 cells	623:634	HEK293 cells	623:634	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	1	18	theme	large	201:205	arg1	libraries					207:215	large libraries	201:215	large libraries created by comprehensive remodeling of the substrate binding pocket	201:283	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	6	19	theme	sites	1066:1070	arg1	mapping					1032:1038	the mapping	1028:1038	the mapping of N-linked glycosylation sites within proteins and proteomes	1028:1100	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	5	20	theme	cells	950:954	arg1	proteome					929:936	the extracellular proteome	911:936	the extracellular proteome of Jurkat T cells	911:954	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	2	21	theme	Asn-containing	412:425	arg1	substrates					427:436	Asn-containing substrates	412:436	Asn-containing substrates	412:436	The engineered variant (chymotrypsiN, ChyB-Asn) demonstrated an altered substrate specificity with an expanded preference for Asn-containing substrates.
31710461	5	22	theme	Jurkat	941:946	arg1	cells					950:954	Jurkat T cells	941:954	Jurkat T cells	941:954	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	6	23	theme	glycosylation	1052:1064	arg1	sites					1066:1070	N-linked glycosylation sites	1043:1070	N-linked glycosylation sites within proteins and proteomes	1043:1100	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	6	24	theme	N-linked	1043:1050	arg1	sites					1066:1070	N-linked glycosylation sites	1043:1070	N-linked glycosylation sites within proteins and proteomes	1043:1100	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	1	25	theme	substrate	111:119	arg1	specificity					121:131	the substrate specificity	107:131	the substrate specificity of chymotrypsin	107:147	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	6	26	link	N-linked	1043:1050	arg1	sites					1066:1070	N-linked glycosylation sites	1043:1070	N-linked glycosylation sites within proteins and proteomes	1043:1100	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	4	27	from	lysates	612:618	arg1	Comparison					557:566	Comparison	557:566	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells	557:634	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	4	28	theme	cells	630:634	arg1	ChyB-Asn					590:597	ChyB-Asn	590:597	ChyB-Asn	590:597	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	4	28	theme	cells	630:634	arg1	ChyB					581:584	wild-type ChyB	571:584	wild-type ChyB	571:584	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	5	29	from	identification	825:838	arg1	proteome					929:936	the extracellular proteome	911:936	the extracellular proteome of Jurkat T cells	911:954	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	4	30	from	ChyB-Asn	590:597	arg1	lysates					612:618	profiling lysates	602:618	profiling lysates	602:618	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	3	31	theme	enzyme	517:522	arg1	stability					500:508	the stability	496:508	the stability of the enzyme	496:522	We confirmed that protein engineering did not compromise the stability of the enzyme by biophysical characterization.
31710461	3	32	theme	protein	457:463	arg1	engineering					465:475	protein engineering	457:475	protein engineering	457:475	We confirmed that protein engineering did not compromise the stability of the enzyme by biophysical characterization.
31710461	4	33	theme	mass	785:788	arg1	spectrometry					790:801	tandem mass spectrometry	778:801	tandem mass spectrometry	778:801	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	4	34	theme	peptides	716:723	arg1	nature					702:707	the nature	698:707	the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry	698:801	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	4	35	dep	peptides	716:723	arg1	the					712:714	the	712:714	the	712:714	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	1	36	theme	libraries	207:215	arg1	screening					188:196	high-throughput screening	172:196	high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket	172:283	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	1	37	theme	comprehensive	228:240	arg1	remodeling					242:251	comprehensive remodeling	228:251	comprehensive remodeling of the substrate binding pocket	228:283	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	0	38	theme	Spectrometry-Based	33:50	arg1	Detection					52:60	Mass Spectrometry-Based Detection	28:60	Mass Spectrometry-Based Detection of Protein Glycosylation	28:85	Engineered ChymotrypsiN for Mass Spectrometry-Based Detection of Protein Glycosylation.
31710461	4	39	theme	ChyB-Asn	590:597	arg1	Comparison					557:566	Comparison	557:566	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells	557:634	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	5	40	theme	T	948:948	arg1	cells					950:954	Jurkat T cells	941:954	Jurkat T cells	941:954	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	0	41	theme	Protein	65:71	arg1	Glycosylation					73:85	Protein Glycosylation	65:85	Protein Glycosylation	65:85	Engineered ChymotrypsiN for Mass Spectrometry-Based Detection of Protein Glycosylation.
31710461	5	42	theme	glycosylated	853:864	arg1	sites					870:874	partially glycosylated Asn sites	843:874	partially glycosylated Asn sites	843:874	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	4	43	theme	profiling	602:610	arg1	lysates					612:618	profiling lysates	602:618	profiling lysates	602:618	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	1	44	theme	chymotrypsin	136:147	arg1	specificity					121:131	the substrate specificity	107:131	the substrate specificity of chymotrypsin	107:147	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	5	45	theme	model	885:889	arg1	glycoprotein					891:902	a model glycoprotein	883:902	a model glycoprotein	883:902	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	2	46	theme	engineered	290:299	arg1	variant					301:307	The engineered variant	286:307	The engineered variant (chymotrypsiN, ChyB-Asn)	286:332	The engineered variant (chymotrypsiN, ChyB-Asn) demonstrated an altered substrate specificity with an expanded preference for Asn-containing substrates.
31710461	4	47	theme	liquid	752:757	arg1	chromatography					759:772	liquid chromatography	752:772	liquid chromatography	752:772	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	2	48	theme	substrate	358:366	arg1	specificity					368:378	an altered substrate specificity	347:378	an altered substrate specificity	347:378	The engineered variant (chymotrypsiN, ChyB-Asn) demonstrated an altered substrate specificity with an expanded preference for Asn-containing substrates.
31710461	2	49	theme	altered	350:356	arg1	specificity					368:378	an altered substrate specificity	347:378	an altered substrate specificity	347:378	The engineered variant (chymotrypsiN, ChyB-Asn) demonstrated an altered substrate specificity with an expanded preference for Asn-containing substrates.
31710461	4	50	theme	quantitative	670:681	arg1	differences					683:693	both qualitative and quantitative differences	649:693	both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry	649:801	Comparison of wild-type ChyB and ChyB-Asn in profiling lysates of HEK293 cells demonstrated both qualitative and quantitative differences in the nature of the peptides and proteins identified by liquid chromatography and tandem mass spectrometry.
31710461	5	51	gly	glycoprotein	891:902	arg1	glycoprotein					891:902	a model glycoprotein	883:902	a model glycoprotein	883:902	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	1	52	theme	substrate	260:268	arg1	pocket					278:283	the substrate binding pocket	256:283	the substrate binding pocket	256:283	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31710461	0	53	theme	Glycosylation	73:85	arg1	Detection					52:60	Mass Spectrometry-Based Detection	28:60	Mass Spectrometry-Based Detection of Protein Glycosylation	28:85	Engineered ChymotrypsiN for Mass Spectrometry-Based Detection of Protein Glycosylation.
31710461	6	54	theme	proteases	1011:1019	arg1	toolkit					1000:1006	the toolkit	996:1006	the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes	996:1100	ChymotrypsiN is a valuable addition to the toolkit of proteases to aid the mapping of N-linked glycosylation sites within proteins and proteomes.
31710461	5	55	theme	extracellular	915:927	arg1	proteome					929:936	the extracellular proteome	911:936	the extracellular proteome of Jurkat T cells	911:954	ChyB-Asn enabled the identification of partially glycosylated Asn sites within a model glycoprotein and in the extracellular proteome of Jurkat T cells.
31710461	2	56	dep	variant	301:307	arg1	chymotrypsiN					310:321	chymotrypsiN	310:321	chymotrypsiN	310:321	The engineered variant (chymotrypsiN, ChyB-Asn) demonstrated an altered substrate specificity with an expanded preference for Asn-containing substrates.
31710461	2	56	dep	variant	301:307	arg1	ChyB-Asn					324:331	ChyB-Asn	324:331	ChyB-Asn	324:331	The engineered variant (chymotrypsiN, ChyB-Asn) demonstrated an altered substrate specificity with an expanded preference for Asn-containing substrates.
31710461	1	57	theme	binding	270:276	arg1	pocket					278:283	the substrate binding pocket	256:283	the substrate binding pocket	256:283	We have engineered the substrate specificity of chymotrypsin to cleave after Asn by high-throughput screening of large libraries created by comprehensive remodeling of the substrate binding pocket.
31271957	2	0	theme	oligosaccharides	429:444	arg1	functionalities					400:414	functionalities	400:414	functionalities	400:414	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	2	0	theme	oligosaccharides	429:444	arg1	pathways					387:394	the biological pathways	372:394	the biological pathways	372:394	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	1	1	dep	-D-GlcNAc	252:260	arg1	1 → 4					245:249	1 → 4	245:249	1 → 4	245:249	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	0	2	theme	Galp	71:74	arg1	unit					87:90	the Galp(1 → 2)Galf unit	67:90	the Galp(1 → 2)Galf unit	67:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	1	3	theme	Hexasaccharide	150:163	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	1	4	theme	-[β-D-Galp-	216:226	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	0	5	from	Synthesis	0:8	arg1	mucins					55:60	Trypanosoma cruzi mucins	37:60	Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit	37:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	4	6	theme	protected	756:764	arg1	unit					783:786	a partially protected galactofuranosyl unit	744:786	a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor	744:847	We discuss the difficulties to introduce a Galp unit at the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor.
31271957	5	7	theme	convergent	898:907	arg1	hexasaccharide					918:931	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	By this route and employing a [3 + 3] nitrilium convergent approach hexasaccharide 1 was synthesized in moderate yield.
31271957	0	8	theme	1 → 2	76:80	arg1	unit					87:90	the Galp(1 → 2)Galf unit	67:90	the Galp(1 → 2)Galf unit	67:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	0	9	from	mucins	55:60	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit	0:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	0	9	from	mucins	55:60	arg1	hexasaccharide					17:30	the hexasaccharide	13:30	the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit	13:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	5	10	theme	approach	909:916	arg1	hexasaccharide					918:931	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	By this route and employing a [3 + 3] nitrilium convergent approach hexasaccharide 1 was synthesized in moderate yield.
31271957	4	11	theme	unit	783:786	arg1	position					732:739	the O-2 position	724:739	the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor	724:847	We discuss the difficulties to introduce a Galp unit at the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor.
31271957	1	12	theme	β-D-Galp-	165:173	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	0	13	theme	Galf	82:85	arg1	unit					87:90	the Galp(1 → 2)Galf unit	67:90	the Galp(1 → 2)Galf unit	67:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	3	14	theme	non-reducing	650:661	arg1	end					663:665	the non-reducing end	646:665	the non-reducing end	646:665	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc was constructed from the reducing to the non-reducing end.
31271957	4	15	theme	galactofuranosyl	766:781	arg1	unit					783:786	a partially protected galactofuranosyl unit	744:786	a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor	744:847	We discuss the difficulties to introduce a Galp unit at the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor.
31271957	4	16	theme	Galp	711:714	arg1	unit					716:719	a Galp unit	709:719	a Galp unit	709:719	We discuss the difficulties to introduce a Galp unit at the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor.
31271957	1	17	from	mucins	288:293	arg1	O-linked					276:283	O-linked	276:283	O-linked	276:283	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	2	18	theme	mucin	423:427	arg1	oligosaccharides					429:444	the mucin oligosaccharides	419:444	the mucin oligosaccharides	419:444	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	4	19	theme	superarmed	832:841	arg1	donor					843:847	an anchimerically superarmed donor	814:847	an anchimerically superarmed donor	814:847	We discuss the difficulties to introduce a Galp unit at the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor.
31271957	1	20	theme	1→ 2	175:178	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	2	21	theme	biological	376:385	arg1	pathways					387:394	the biological pathways	372:394	the biological pathways	372:394	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	5	22	theme	[3 + 3	880:885	arg1	hexasaccharide					918:931	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	By this route and employing a [3 + 3] nitrilium convergent approach hexasaccharide 1 was synthesized in moderate yield.
31271957	0	23	theme	hexasaccharide	17:30	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit	0:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	1	24	theme	-β-D-Galf-	234:243	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	1	25	theme	-[β-D-Galp-	180:190	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	1	26	theme	Trypanosoma	298:308	arg1	epimastigotes					316:328	Trypanosoma cruzi epimastigotes	298:328	Trypanosoma cruzi epimastigotes	298:328	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	5	27	theme	nitrilium	888:896	arg1	hexasaccharide					918:931	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	a [3 + 3] nitrilium convergent approach hexasaccharide 1	878:933	By this route and employing a [3 + 3] nitrilium convergent approach hexasaccharide 1 was synthesized in moderate yield.
31271957	0	28	theme	Trypanosoma	37:47	arg1	mucins					55:60	Trypanosoma cruzi mucins	37:60	Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit	37:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	0	29	theme	superarmed	111:120	arg1	donor					143:147	a superarmed thiogalactopyranosyl donor	109:147	a superarmed thiogalactopyranosyl donor	109:147	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	3	30	theme	Trisaccharide	540:552	arg1	-D-GlcNAc					599:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc was constructed from the reducing to the non-reducing end.
31271957	1	31	theme	1 → 3	192:196	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	1	32	theme	epimastigotes	316:328	arg1	mucins					288:293	mucins	288:293	mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes	288:358	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	1	33	from	O-linked	276:283	arg1	mucins					288:293	mucins	288:293	mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes	288:358	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	2	34	theme	insect	527:532	arg1	host					534:537	the insect host	523:537	the insect host	523:537	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	0	35	dep	Trypanosoma	37:47	arg1	cruzi					49:53	cruzi	49:53	cruzi	49:53	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	0	36	theme	thiogalactopyranosyl	122:141	arg1	donor					143:147	a superarmed thiogalactopyranosyl donor	109:147	a superarmed thiogalactopyranosyl donor	109:147	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	1	37	theme	metacyclic	334:343	arg1	trypomatigotes					345:358	metacyclic trypomatigotes	334:358	metacyclic trypomatigotes	334:358	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	3	38	theme	-β-D-Galf-	582:591	arg1	-D-GlcNAc					599:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc was constructed from the reducing to the non-reducing end.
31271957	2	39	with	interactions	486:497	arg1	host					534:537	the insect host	523:537	the insect host	523:537	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	5	40	theme	moderate	954:961	arg1	yield					963:967	moderate yield	954:967	moderate yield	954:967	By this route and employing a [3 + 3] nitrilium convergent approach hexasaccharide 1 was synthesized in moderate yield.
31271957	1	41	theme	trypomatigotes	345:358	arg1	mucins					288:293	mucins	288:293	mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes	288:358	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	3	42	theme	1 → 2	576:580	arg1	-D-GlcNAc					599:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc was constructed from the reducing to the non-reducing end.
31271957	3	43	theme	constituent	554:564	arg1	-D-GlcNAc					599:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc was constructed from the reducing to the non-reducing end.
31271957	2	44	theme	molecules	508:516	arg1	interactions					486:497	the interactions	482:497	the interactions of these molecules with the insect host	482:537	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	0	45	with	mucins	55:60	arg1	unit					87:90	the Galp(1 → 2)Galf unit	67:90	the Galp(1 → 2)Galf unit	67:90	Synthesis of the hexasaccharide from Trypanosoma cruzi mucins with the Galp(1 → 2)Galf unit constructed with a superarmed thiogalactopyranosyl donor.
31271957	1	46	theme	-β-D-Galp-	199:208	arg1	-D-GlcNAc					252:260	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1)	150:264	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	3	47	theme	β-D-Galp-	566:574	arg1	-D-GlcNAc					599:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc	540:607	Trisaccharide constituent β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)-D-GlcNAc was constructed from the reducing to the non-reducing end.
31271957	1	48	dep	Trypanosoma	298:308	arg1	cruzi					310:314	cruzi	310:314	cruzi	310:314	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31271957	4	49	theme	O-2	728:730	arg1	position					732:739	the O-2 position	724:739	the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor	724:847	We discuss the difficulties to introduce a Galp unit at the O-2 position of a partially protected galactofuranosyl unit which were overcome using an anchimerically superarmed donor.
31271957	2	50	from	Studies	361:367	arg1	functionalities					400:414	functionalities	400:414	functionalities	400:414	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	2	50	from	Studies	361:367	arg1	pathways					387:394	the biological pathways	372:394	the biological pathways	372:394	Studies on the biological pathways and functionalities of the mucin oligosaccharides are prompted in order to understand the interactions of these molecules with the insect host.
31271957	1	51	attach	O-linked	276:283	arg3	mucins					288:293	mucins	288:293	mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes	288:358	Hexasaccharide β-D-Galp-(1→ 2)-[β-D-Galp-(1 → 3)]-β-D-Galp-(1 → 6)-[β-D-Galp-(1 → 2)-β-D-Galf-(1 → 4)]-D-GlcNAc (1) was found O-linked in mucins of Trypanosoma cruzi epimastigotes and metacyclic trypomatigotes.
31139149	5	0	theme	nutritional	1347:1357	arg1	stress					1359:1364	nutritional stress	1347:1364	nutritional stress reproduced in colon cancer cells	1347:1397	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	4	1	theme	levels	720:725	arg1	modification					688:699	the modification	684:699	the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA),	684:861	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	6	2	theme	sensing	1533:1539	arg1	pathway					1541:1547	HBP/O-GlcNAcylation nutrient sensing pathway	1504:1547	HBP/O-GlcNAcylation nutrient sensing pathway	1504:1547	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	1	3	theme	nucleocytoplasmic	176:192	arg1	proteins					194:201	nucleocytoplasmic proteins	176:201	nucleocytoplasmic proteins	176:201	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	5	4	theme	OGT	1231:1233	arg1	inhibition					1235:1244	OGT inhibition	1231:1244	OGT inhibition	1231:1244	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	6	5	theme	important	1598:1606	arg1	mechanism					1617:1625	an important survival mechanism	1595:1625	an important survival mechanism in cancer cells	1595:1641	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	2	6	theme	CSC	373:375	arg1	phenotype					377:385	CSC phenotype	373:385	CSC phenotype	373:385	However, the role played by this modification in the establishment of CSC phenotype has been poorly studied so far and remains unclear.
31139149	4	7	theme	cell-like	1029:1037	arg1	subpopulation					1039:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation	985:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	985:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	0	8	theme	Cancer	87:92	arg1	Cells					94:98	Colon Cancer Cells	81:98	Colon Cancer Cells	81:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	5	9	theme	colon	1380:1384	arg1	cells					1393:1397	colon cancer cells	1380:1397	colon cancer cells	1380:1397	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	6	10	theme	cancer	1630:1635	arg1	cells					1637:1641	cancer cells	1630:1641	cancer cells	1630:1641	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	4	11	theme	stem	1024:1027	arg1	subpopulation					1039:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation	985:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	985:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	1	12	theme	cancer	295:300	arg1	hallmarks					282:290	several hallmarks	274:290	several hallmarks of cancer	274:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	0	13	theme	Colon	81:85	arg1	Cells					94:98	Colon Cancer Cells	81:98	Colon Cancer Cells	81:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	3	14	theme	non-malignant	561:573	arg1	cells					575:579	non-malignant cells	561:579	non-malignant cells	561:579	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	2	15	theme	phenotype	377:385	arg1	establishment					356:368	the establishment	352:368	the establishment of CSC phenotype	352:385	However, the role played by this modification in the establishment of CSC phenotype has been poorly studied so far and remains unclear.
31139149	5	16	theme	nutritional	1294:1304	arg1	stress					1306:1311	severe nutritional stress	1287:1311	severe nutritional stress	1287:1311	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	4	17	theme	O-GlcNAcylation	704:718	arg1	levels					720:725	O-GlcNAcylation levels	704:725	O-GlcNAcylation levels	704:725	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	18	theme	pharmacological	730:744	arg1	inhibition					746:755	pharmacological inhibition	730:755	pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT)	730:815	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	5	19	theme	OGT	1425:1427	arg1	inhibition					1429:1438	OGT inhibition	1425:1438	OGT inhibition	1425:1438	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	3	20	theme	basal	543:547	arg1	levels					549:554	higher O-GlcNAc basal levels	527:554	higher O-GlcNAc basal levels than non-malignant cells	527:579	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	5	21	theme	stress	1306:1311	arg1	presence					1275:1282	the presence	1271:1282	the presence of severe nutritional stress	1271:1311	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	4	22	theme	malignant	933:941	arg1	lines					948:952	our colon malignant cell lines	923:952	our colon malignant cell lines	923:952	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	6	23	theme	O-GlcNAc	1559:1566	arg1	sensor					1577:1582	O-GlcNAc nutrient sensor	1559:1582	O-GlcNAc nutrient sensor	1559:1582	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	6	24	theme	survival	1608:1615	arg1	mechanism					1617:1625	an important survival mechanism	1595:1625	an important survival mechanism in cancer cells	1595:1641	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	4	25	theme	aggressive	1103:1112	arg1	phenotype					1124:1132	very aggressive malignant phenotype	1098:1132	very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	1098:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	26	theme	cell	943:946	arg1	lines					948:952	our colon malignant cell lines	923:952	our colon malignant cell lines	923:952	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	27	theme	positive	994:1001	arg1	subpopulation					1039:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation	985:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	985:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	28	theme	formation	1179:1187	arg1	abilities					1189:1197	spheroid formation abilities	1170:1197	spheroid formation abilities	1170:1197	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	29	theme	O-GlcNAc-transferase	764:783	arg1	enzyme					785:790	the O-GlcNAc-transferase enzyme	760:790	the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT)	760:815	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	30	theme	double	987:992	arg1	subpopulation					1039:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation	985:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	985:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	31	theme	3D	1202:1203	arg1	culture					1205:1211	3D culture	1202:1211	3D culture	1202:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	32	theme	CD44+/CD133+	1004:1015	arg1	subpopulation					1039:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation	985:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	985:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	5	33	theme	cancer	1386:1391	arg1	cells					1393:1397	colon cancer cells	1380:1397	colon cancer cells	1380:1397	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	4	34	theme	markers	905:911	arg1	expression					877:886	the expression	873:886	the expression of all stem cell markers tested in our colon malignant cell lines	873:952	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	6	35	theme	nutritional	1649:1659	arg1	conditions					1671:1680	nutritional stressful conditions	1649:1680	nutritional stressful conditions	1649:1680	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	0	36	dep	Markers	59:65	arg1	Expression					67:76	Expression	67:76	Stem Cell Markers Expression in Colon Cancer Cells	49:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	5	37	dep	demonstrated	1329:1340	arg1	effects					1403:1409	the effects obtained with OGT inhibition	1399:1438	the effects obtained with OGT inhibition	1399:1438	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	1	38	theme	key	220:222	arg1	regulator					224:232	a key regulator	218:232	a key regulator of diverse cellular processes including several hallmarks of cancer	218:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	4	39	theme	malignant	1114:1122	arg1	phenotype					1124:1132	very aggressive malignant phenotype	1098:1132	very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	1098:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	40	theme	cell	900:903	arg1	markers					905:911	all stem cell markers	891:911	all stem cell markers tested in our colon malignant cell lines	891:952	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	3	41	theme	phenotype	659:667	arg1	regulation					641:650	the regulation	637:650	the regulation of CSC phenotype	637:667	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	1	42	theme	proteins	194:201	arg1	modification					160:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification	101:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins	101:201	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	3	43	theme	cancer	506:511	arg1	cells					513:517	colon cancer cells	500:517	colon cancer cells	500:517	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	0	44	from	Expression	67:76	arg1	Cells					94:98	Colon Cancer Cells	81:98	Colon Cancer Cells	81:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	0	45	gly	O-GlcNAcylation	0:14	arg1	Regulation					35:44	the Regulation	31:44	the Regulation of Stem Cell Markers Expression in Colon Cancer Cells	31:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	5	46	theme	severe	1287:1292	arg1	stress					1306:1311	severe nutritional stress	1287:1311	severe nutritional stress	1287:1311	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	6	47	theme	nutrient	1568:1575	arg1	sensor					1577:1582	O-GlcNAc nutrient sensor	1559:1582	O-GlcNAc nutrient sensor	1559:1582	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	1	48	theme	diverse	237:243	arg1	processes					254:262	diverse cellular processes	237:262	diverse cellular processes including several hallmarks of cancer	237:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	1	48	theme	diverse	237:243	arg1	hallmarks					282:290	several hallmarks	274:290	several hallmarks of cancer	274:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	0	49	theme	Stem	49:52	arg1	Markers					59:65	Stem Cell Markers	49:65	Stem Cell Markers Expression in Colon Cancer Cells	49:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	4	50	theme	colon	927:931	arg1	lines					948:952	our colon malignant cell lines	923:952	our colon malignant cell lines	923:952	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	6	51	from	mechanism	1617:1625	arg1	cells					1637:1641	cancer cells	1630:1641	cancer cells	1630:1641	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	3	52	theme	CSC	655:657	arg1	phenotype					659:667	CSC phenotype	655:667	CSC phenotype	655:667	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	4	53	from	clonogenicity	1152:1164	arg1	culture					1205:1211	3D culture	1202:1211	3D culture	1202:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	54	theme	increased	1142:1150	arg1	clonogenicity					1152:1164	increased clonogenicity	1142:1164	increased clonogenicity	1142:1164	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	3	55	theme	colon	500:504	arg1	cells					513:517	colon cancer cells	500:517	colon cancer cells	500:517	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	4	56	from	abilities	1189:1197	arg1	culture					1205:1211	3D culture	1202:1211	3D culture	1202:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	57	theme	enzyme	833:838	arg1	modification					688:699	the modification	684:699	the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA),	684:861	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	4	58	theme	spheroid	1170:1177	arg1	abilities					1189:1197	spheroid formation abilities	1170:1197	spheroid formation abilities	1170:1197	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	1	59	theme	dynamic	105:111	arg1	modification					160:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification	101:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins	101:201	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	6	60	theme	nutrient	1524:1531	arg1	pathway					1541:1547	HBP/O-GlcNAcylation nutrient sensing pathway	1504:1547	HBP/O-GlcNAcylation nutrient sensing pathway	1504:1547	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	4	61	theme	stem	895:898	arg1	markers					905:911	all stem cell markers	891:911	all stem cell markers tested in our colon malignant cell lines	891:952	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	6	62	theme	stressful	1661:1669	arg1	conditions					1671:1680	nutritional stressful conditions	1649:1680	nutritional stressful conditions	1649:1680	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	1	63	theme	O-linked-N-acetylglucosamine	113:140	arg1	modification					160:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification	101:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins	101:201	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	4	64	theme	subpopulation	1039:1051	arg1	appearance					971:980	the appearance	967:980	the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	967:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	1	65	theme	cellular	245:252	arg1	processes					254:262	diverse cellular processes	237:262	diverse cellular processes including several hallmarks of cancer	237:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	1	65	theme	cellular	245:252	arg1	hallmarks					282:290	several hallmarks	274:290	several hallmarks of cancer	274:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	6	66	theme	HBP/O-GlcNAcylation	1504:1522	arg1	pathway					1541:1547	HBP/O-GlcNAcylation nutrient sensing pathway	1504:1547	HBP/O-GlcNAcylation nutrient sensing pathway	1504:1547	Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions.
31139149	4	67	theme	enzyme	785:790	arg1	inhibition					746:755	pharmacological inhibition	730:755	pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT)	730:815	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	1	68	theme	posttranslational	142:158	arg1	modification					160:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification	101:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins	101:201	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	1	69	theme	processes	254:262	arg1	regulator					224:232	a key regulator	218:232	a key regulator of diverse cellular processes including several hallmarks of cancer	218:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	0	70	theme	Markers	59:65	arg1	Regulation					35:44	the Regulation	31:44	the Regulation of Stem Cell Markers Expression in Colon Cancer Cells	31:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	1	71	mod	modification	160:171	arg3	O-linked-N-acetylglucosamine					113:140	The dynamic O-linked-N-acetylglucosamine posttranslational modification	101:171	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins	101:201	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	1	71	mod	modification	160:171	arg1	proteins					194:201	nucleocytoplasmic proteins	176:201	nucleocytoplasmic proteins	176:201	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
31139149	3	72	theme	previous	470:477	arg1	reports					479:485	the previous reports	466:485	the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells	466:579	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	3	73	theme	higher	527:532	arg1	levels					549:554	higher O-GlcNAc basal levels	527:554	higher O-GlcNAc basal levels than non-malignant cells	527:579	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	5	74	dep	effects	1403:1409	arg1	stress					1359:1364	nutritional stress	1347:1364	nutritional stress reproduced in colon cancer cells	1347:1397	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	5	74	dep	effects	1403:1409	arg1	obtained					1411:1418	obtained	1411:1418	obtained with OGT inhibition	1411:1438	We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition.
31139149	0	75	theme	Cell	54:57	arg1	Markers					59:65	Stem Cell Markers	49:65	Stem Cell Markers Expression in Colon Cancer Cells	49:98	O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells.
31139149	3	76	theme	O-GlcNAc	534:541	arg1	levels					549:554	higher O-GlcNAc basal levels	527:554	higher O-GlcNAc basal levels than non-malignant cells	527:579	In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype.
31139149	4	77	theme	small	1018:1022	arg1	subpopulation					1039:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation	985:1051	a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture	985:1211	We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1-10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture.
31139149	1	78	theme	several	274:280	arg1	hallmarks					282:290	several hallmarks	274:290	several hallmarks of cancer	274:300	The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer.
30904668	0	0	theme	covalent	80:87	arg1	linkage					89:95	covalent linkage	80:95	covalent linkage of mannoprotein to the cell wall	80:128	Aspergillus fumigatus Mnn9 is responsible for mannan synthesis and required for covalent linkage of mannoprotein to the cell wall.
30904668	6	1	theme	N-glycan	837:844	arg1	synthesis					846:854	N-glycan synthesis	837:854	N-glycan synthesis	837:854	Although there was no major effect on N-glycan synthesis, covalently-linked cell wall mannoprotein Mp1 was significantly reduced in the mutant.
30904668	7	2	from	formation	1032:1040	arg1	mannoproteins					1071:1083	cell wall mannoproteins	1061:1083	cell wall mannoproteins	1061:1083	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	7	3	theme	α-mannan	1049:1056	arg1	formation					1032:1040	the formation	1028:1040	the formation of the α-mannan in cell wall mannoproteins	1028:1083	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	3	4	theme	long	468:471	arg1	time					473:476	a long time	466:476	a long time	466:476	Although galactomannan has been used as a diagnostic target for a long time, its biosynthesis remains unknown in A. fumigatus.
30904668	7	5	theme	mannose	1125:1131	arg1	chains					1133:1138	O-linked mannose chains	1116:1138	O-linked mannose chains	1116:1138	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	3	6	used	used	434:437	arg2	galactomannan					411:423	galactomannan	411:423	galactomannan	411:423	Although galactomannan has been used as a diagnostic target for a long time, its biosynthesis remains unknown in A. fumigatus.
30904668	3	6	used	used	434:437	arg2	target					455:460	a diagnostic target	442:460	a diagnostic target for a long time	442:476	Although galactomannan has been used as a diagnostic target for a long time, its biosynthesis remains unknown in A. fumigatus.
30904668	1	7	theme	cell	244:247	arg1	target					300:305	a promising antifungal target	277:305	a promising antifungal target	277:305	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	1	7	theme	cell	244:247	arg1	wall					249:252	its cell wall	240:252	its cell wall	240:252	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	7	8	theme	chains	1133:1138	arg1	elongation					1102:1111	elongation	1102:1111	elongation of O-linked mannose chains	1102:1138	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	6	9	theme	major	821:825	arg1	effect					827:832	no major effect	818:832	no major effect	818:832	Although there was no major effect on N-glycan synthesis, covalently-linked cell wall mannoprotein Mp1 was significantly reduced in the mutant.
30904668	7	10	link	O-linked	1116:1123	arg1	chains					1133:1138	O-linked mannose chains	1116:1138	O-linked mannose chains	1116:1138	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	5	11	theme	wall	760:763	arg1	components					765:774	reduced cell wall components	747:774	reduced cell wall components	747:774	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	1	12	theme	antifungal	289:298	arg1	target					300:305	a promising antifungal target	277:305	a promising antifungal target	277:305	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	1	12	theme	antifungal	289:298	arg1	wall					249:252	its cell wall	240:252	its cell wall	240:252	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	5	13	theme	abnormal	780:787	arg1	polarity					789:796	abnormal polarity	780:796	abnormal polarity	780:796	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	0	14	theme	mannoprotein	100:111	arg1	linkage					89:95	covalent linkage	80:95	covalent linkage of mannoprotein to the cell wall	80:128	Aspergillus fumigatus Mnn9 is responsible for mannan synthesis and required for covalent linkage of mannoprotein to the cell wall.
30904668	6	15	theme	covalently-linked	857:873	arg1	Mp1					898:900	covalently-linked cell wall mannoprotein Mp1	857:900	covalently-linked cell wall mannoprotein Mp1	857:900	Although there was no major effect on N-glycan synthesis, covalently-linked cell wall mannoprotein Mp1 was significantly reduced in the mutant.
30904668	0	16	theme	Aspergillus	0:10	arg1	Mnn9					22:25	Aspergillus fumigatus Mnn9	0:25	Aspergillus fumigatus Mnn9	0:25	Aspergillus fumigatus Mnn9 is responsible for mannan synthesis and required for covalent linkage of mannoprotein to the cell wall.
30904668	7	17	theme	responsible	1012:1022	arg1	Mnn9p					981:985	Mnn9p	981:985	Mnn9p	981:985	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	7	17	theme	responsible	1012:1022	arg1	mannosyltransferase					992:1010	a mannosyltransferase	990:1010	a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins	990:1083	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	0	18	theme	cell	120:123	arg1	wall					125:128	the cell wall	116:128	the cell wall	116:128	Aspergillus fumigatus Mnn9 is responsible for mannan synthesis and required for covalent linkage of mannoprotein to the cell wall.
30904668	5	19	theme	cell	755:758	arg1	components					765:774	reduced cell wall components	747:774	reduced cell wall components	747:774	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	5	20	theme	reduced	747:753	arg1	components					765:774	reduced cell wall components	747:774	reduced cell wall components	747:774	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	1	21	theme	essential	144:152	arg1	role					154:157	the essential role	140:157	the essential role in protection of the Aspergillus fumigatus cell against human defense reactions	140:237	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	1	22	theme	Aspergillus	180:190	arg1	cell					202:205	the Aspergillus fumigatus cell	176:205	the Aspergillus fumigatus cell	176:205	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	7	23	theme	wall	1066:1069	arg1	mannoproteins					1071:1083	cell wall mannoproteins	1061:1083	cell wall mannoproteins	1061:1083	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	6	24	theme	mannoprotein	885:896	arg1	Mp1					898:900	covalently-linked cell wall mannoprotein Mp1	857:900	covalently-linked cell wall mannoprotein Mp1	857:900	Although there was no major effect on N-glycan synthesis, covalently-linked cell wall mannoprotein Mp1 was significantly reduced in the mutant.
30904668	5	25	theme	hygromycin	720:729	arg1	B					731:731	hygromycin B	720:731	hygromycin B	720:731	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	6	26	theme	wall	880:883	arg1	Mp1					898:900	covalently-linked cell wall mannoprotein Mp1	857:900	covalently-linked cell wall mannoprotein Mp1	857:900	Although there was no major effect on N-glycan synthesis, covalently-linked cell wall mannoprotein Mp1 was significantly reduced in the mutant.
30904668	5	27	theme	increased	663:671	arg1	sensitivity					673:683	an increased sensitivity	660:683	an increased sensitivity to calcofluor white, Congo red, or hygromycin B	660:731	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	7	28	theme	cell	1061:1064	arg1	mannoproteins					1071:1083	cell wall mannoproteins	1061:1083	cell wall mannoproteins	1061:1083	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	4	29	theme	gene	580:583	arg1	mnn9					585:588	a putative α1,6-mannosyltransferase gene mnn9	544:588	a putative α1,6-mannosyltransferase gene mnn9	544:588	In this study, a putative α1,6-mannosyltransferase gene mnn9 was identified in A. fumigatus.
30904668	1	30	theme	cell	202:205	arg1	protection					162:171	protection	162:171	protection of the Aspergillus fumigatus cell against human defense reactions	162:237	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	6	31	theme	cell	875:878	arg1	Mp1					898:900	covalently-linked cell wall mannoprotein Mp1	857:900	covalently-linked cell wall mannoprotein Mp1	857:900	Although there was no major effect on N-glycan synthesis, covalently-linked cell wall mannoprotein Mp1 was significantly reduced in the mutant.
30904668	2	32	theme	cell	312:315	arg1	wall					317:320	The cell wall	308:320	The cell wall of A. fumigatus	308:336	The cell wall of A. fumigatus composed of chitin, glucan and galactomannan and mannoproteins.
30904668	0	33	theme	mannan	46:51	arg1	synthesis					53:61	mannan synthesis	46:61	mannan synthesis	46:61	Aspergillus fumigatus Mnn9 is responsible for mannan synthesis and required for covalent linkage of mannoprotein to the cell wall.
30904668	1	34	theme	promising	279:287	arg1	target					300:305	a promising antifungal target	277:305	a promising antifungal target	277:305	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	1	34	theme	promising	279:287	arg1	wall					249:252	its cell wall	240:252	its cell wall	240:252	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	7	35	theme	O-linked	1116:1123	arg1	chains					1133:1138	O-linked mannose chains	1116:1138	O-linked mannose chains	1116:1138	Based on our results, we propose that Mnn9p is a mannosyltransferase responsible for the formation of the α-mannan in cell wall mannoproteins, potentially via elongation of O-linked mannose chains.
30904668	0	36	dep	Aspergillus	0:10	arg1	fumigatus					12:20	fumigatus	12:20	fumigatus	12:20	Aspergillus fumigatus Mnn9 is responsible for mannan synthesis and required for covalent linkage of mannoprotein to the cell wall.
30904668	5	37	theme	mnn9	638:641	arg1	gene					643:646	the mnn9 gene	634:646	the mnn9 gene	634:646	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	6	38	link	covalently-linked	857:873	arg1	Mp1					898:900	covalently-linked cell wall mannoprotein Mp1	857:900	covalently-linked cell wall mannoprotein Mp1	857:900	Although there was no major effect on N-glycan synthesis, covalently-linked cell wall mannoprotein Mp1 was significantly reduced in the mutant.
30904668	4	39	theme	putative	546:553	arg1	mnn9					585:588	a putative α1,6-mannosyltransferase gene mnn9	544:588	a putative α1,6-mannosyltransferase gene mnn9	544:588	In this study, a putative α1,6-mannosyltransferase gene mnn9 was identified in A. fumigatus.
30904668	5	40	theme	gene	643:646	arg1	Deletion					622:629	Deletion	622:629	Deletion of the mnn9 gene	622:646	Deletion of the mnn9 gene resulted in an increased sensitivity to calcofluor white, Congo red, or hygromycin B as well as in reduced cell wall components and abnormal polarity.
30904668	3	41	theme	diagnostic	444:453	arg1	target					455:460	a diagnostic target	442:460	a diagnostic target for a long time	442:476	Although galactomannan has been used as a diagnostic target for a long time, its biosynthesis remains unknown in A. fumigatus.
30904668	3	41	theme	diagnostic	444:453	arg1	galactomannan					411:423	galactomannan	411:423	galactomannan	411:423	Although galactomannan has been used as a diagnostic target for a long time, its biosynthesis remains unknown in A. fumigatus.
30904668	1	42	theme	human	215:219	arg1	reactions					229:237	human defense reactions	215:237	human defense reactions	215:237	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	2	43	theme	fumigatus	328:336	arg1	wall					317:320	The cell wall	308:320	The cell wall of A. fumigatus	308:336	The cell wall of A. fumigatus composed of chitin, glucan and galactomannan and mannoproteins.
30904668	1	44	theme	defense	221:227	arg1	reactions					229:237	human defense reactions	215:237	human defense reactions	215:237	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	1	45	dep	Aspergillus	180:190	arg1	fumigatus					192:200	fumigatus	192:200	fumigatus	192:200	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	1	46	from	role	154:157	arg1	protection					162:171	protection	162:171	protection of the Aspergillus fumigatus cell against human defense reactions	162:237	Owing to the essential role in protection of the Aspergillus fumigatus cell against human defense reactions, its cell wall has long been taken as a promising antifungal target.
30904668	4	47	theme	α1,6-mannosyltransferase	555:578	arg1	mnn9					585:588	a putative α1,6-mannosyltransferase gene mnn9	544:588	a putative α1,6-mannosyltransferase gene mnn9	544:588	In this study, a putative α1,6-mannosyltransferase gene mnn9 was identified in A. fumigatus.
30919021	9	0	from	residues	1184:1191	arg1	hydroxylation					1150:1162	hydroxylation	1150:1162	hydroxylation at specific proline residues	1150:1191	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	8	1	theme	collagen	949:956	arg1	1α1					958:960	collagen 1α1	949:960	collagen 1α1	949:960	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	5	2	gly	glycosylation	577:589	arg1	P4HA1					594:598	P4HA1	594:598	P4HA1	594:598	N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion.
30919021	5	3	theme	1α2	651:653	arg1	secretion					655:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion.
30919021	9	4	link	N-linked	1107:1114	arg1	glycosylation					1116:1128	N-linked glycosylation	1107:1128	N-linked glycosylation of P4HA1	1107:1137	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	1	5	theme	prolyl	226:231	arg1	4-hydroxylase					233:245	prolyl 4-hydroxylase subunit α 1 (P4HA1)	226:265	prolyl 4-hydroxylase subunit α 1 (P4HA1)	226:265	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	5	6	theme	enhanced	616:623	arg1	secretion					655:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion.
30919021	9	7	theme	P4HA1	1133:1137	arg1	glycosylation					1116:1128	N-linked glycosylation	1107:1128	N-linked glycosylation of P4HA1	1107:1137	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	7	8	theme	decreased	789:797	arg1	hydroxylation					799:811	decreased hydroxylation	789:811	decreased hydroxylation	789:811	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	1	9	theme	4-hydroxylase	233:245	arg1	activity					214:221	the activity	210:221	the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1)	210:265	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	5	10	theme	pepsin-resistant	625:640	arg1	secretion					655:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion.
30919021	8	11	located	found	1059:1063	arg2	hydroxylation					1042:1054	increased proline hydroxylation	1024:1054	increased proline hydroxylation	1024:1054	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	8	11	located	found	1059:1063	arg1	sites					1073:1077	four sites	1068:1077	four sites	1068:1077	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	9	12	theme	N-linked	1107:1114	arg1	glycosylation					1116:1128	N-linked glycosylation	1107:1128	N-linked glycosylation of P4HA1	1107:1137	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	1	13	dep	acid	133:136	arg1	VC					150:151	VC	150:151	VC	150:151	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	1	13	dep	acid	133:136	arg1	C					147:147	vitamin C	139:147	vitamin C	139:147	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	7	14	theme	Stt3b-silenced	761:774	arg1	fibroblasts					776:786	Stt3b-silenced fibroblasts	761:786	Stt3b-silenced fibroblasts	761:786	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	1	15	theme	subunit	247:253	arg1	α					255:255	subunit α 1	247:257	prolyl 4-hydroxylase subunit α 1 (P4HA1)	226:265	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	1	15	theme	subunit	247:253	arg1	P4HA1					260:264	P4HA1	260:264	P4HA1	260:264	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	0	16	theme	I	112:112	arg1	collagen					114:121	type I collagen	107:121	type I collagen	107:121	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	8	17	theme	proline	971:977	arg1	hydroxylation					979:991	reduced proline hydroxylation	963:991	reduced proline hydroxylation	963:991	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	4	18	theme	N113	501:504	arg1	glycosylation					470:482	glycosylation	470:482	glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1)	470:550	Our studies show that glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1) is augmented by VC.
30919021	6	19	from	glycans	713:719	arg1	P4HA1					724:728	P4HA1	724:728	P4HA1	724:728	Downregulation of Stt3b and Magt1 reduces N259 glycans on P4HA1.
30919021	0	20	theme	type	107:110	arg1	collagen					114:121	type I collagen	107:121	type I collagen	107:121	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	8	21	theme	reduced	963:969	arg1	hydroxylation					979:991	reduced proline hydroxylation	963:991	reduced proline hydroxylation	963:991	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	2	22	theme	glycosylation	340:352	arg1	role					323:326	the role	319:326	the role	319:326	To explore the mechanism involved, we investigated the role of N-linked glycosylation, which can regulate enzyme activity.
30919021	0	23	theme	inducible	10:18	arg1	glycans					25:31	Ascorbate inducible N259 glycans	0:31	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit	0:63	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	9	24	theme	collagen	1204:1211	arg1	maturation					1213:1222	collagen maturation	1204:1222	collagen maturation	1204:1222	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	6	25	theme	Magt1	694:698	arg1	Downregulation					666:679	Downregulation	666:679	Downregulation of Stt3b and Magt1	666:698	Downregulation of Stt3b and Magt1 reduces N259 glycans on P4HA1.
30919021	2	26	theme	N-linked	331:338	arg1	glycosylation					340:352	N-linked glycosylation	331:352	N-linked glycosylation	331:352	To explore the mechanism involved, we investigated the role of N-linked glycosylation, which can regulate enzyme activity.
30919021	0	27	theme	Ascorbate	0:8	arg1	glycans					25:31	Ascorbate inducible N259 glycans	0:31	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit	0:63	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	7	28	located	found	816:820	arg1	1α2					743:745	collagen 1α2	734:745	collagen 1α2 purified from Stt3b-silenced fibroblasts	734:786	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	7	28	located	found	816:820	arg1	residues					847:854	five specific proline residues	825:854	five specific proline residues	825:854	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	7	28	located	found	816:820	arg2	hydroxylation					799:811	decreased hydroxylation	789:811	decreased hydroxylation	789:811	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	7	29	theme	proline	839:845	arg1	residues					847:854	five specific proline residues	825:854	five specific proline residues	825:854	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	7	30	theme	collagen	734:741	arg1	1α2					743:745	collagen 1α2	734:745	collagen 1α2 purified from Stt3b-silenced fibroblasts	734:786	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	9	31	gly	glycosylation	1116:1128	arg1	P4HA1					1133:1137	P4HA1	1133:1137	P4HA1	1133:1137	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	9	31	gly	glycosylation	1116:1128	arg1	collagen					1204:1211	collagen maturation	1204:1222	collagen maturation	1204:1222	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	6	32	theme	N259	708:711	arg1	glycans					713:719	N259 glycans	708:719	N259 glycans on P4HA1	708:728	Downregulation of Stt3b and Magt1 reduces N259 glycans on P4HA1.
30919021	2	33	theme	enzyme	374:379	arg1	activity					381:388	enzyme activity	374:388	enzyme activity	374:388	To explore the mechanism involved, we investigated the role of N-linked glycosylation, which can regulate enzyme activity.
30919021	0	34	theme	N259	20:23	arg1	glycans					25:31	Ascorbate inducible N259 glycans	0:31	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit	0:63	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	0	35	theme	collagen	114:121	arg1	hydroxylation					76:88	hydroxylation	76:88	hydroxylation	76:88	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	0	35	theme	collagen	114:121	arg1	secretion					94:102	secretion	94:102	secretion	94:102	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	2	36	link	N-linked	331:338	arg1	glycosylation					340:352	N-linked glycosylation	331:352	N-linked glycosylation	331:352	To explore the mechanism involved, we investigated the role of N-linked glycosylation, which can regulate enzyme activity.
30919021	7	37	theme	increased	877:885	arg1	hydroxylation					887:899	significantly increased hydroxylation	863:899	significantly increased hydroxylation	863:899	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	0	38	theme	prolyl	36:41	arg1	subunit					57:63	prolyl 4-hydroxylase subunit	36:63	prolyl 4-hydroxylase subunit	36:63	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	4	39	theme	N259	487:490	arg1	glycosylation					470:482	glycosylation	470:482	glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1)	470:550	Our studies show that glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1) is augmented by VC.
30919021	1	40	theme	mature	181:186	arg1	collagen					188:195	mature collagen	181:195	mature collagen	181:195	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	9	41	theme	specific	1167:1174	arg1	residues					1184:1191	specific proline residues	1167:1191	specific proline residues	1167:1191	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	4	42	gly	glycosylation	470:482	arg1	N113					501:504	N113	501:504	N113	501:504	Our studies show that glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1) is augmented by VC.
30919021	4	42	gly	glycosylation	470:482	arg1	N259					487:490	N259	487:490	N259	487:490	Our studies show that glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1) is augmented by VC.
30919021	1	43	theme	collagen	188:195	arg1	secretion					168:176	the secretion	164:176	the secretion of mature collagen	164:195	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	8	44	theme	increased	1024:1032	arg1	hydroxylation					1042:1054	increased proline hydroxylation	1024:1054	increased proline hydroxylation	1024:1054	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	9	45	theme	proline	1176:1182	arg1	residues					1184:1191	specific proline residues	1167:1191	specific proline residues	1167:1191	These results suggest that N-linked glycosylation of P4HA1 can direct hydroxylation at specific proline residues and affect collagen maturation.
30919021	3	46	gly	glycosylation	405:417	arg2	Asn					426:428	Asn	426:428	Asn (N) 113	426:436	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	46	gly	glycosylation	405:417	arg2	sites					419:423	two glycosylation sites	401:423	two glycosylation sites	401:423	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	46	gly	glycosylation	405:417	arg2	N259					442:445	N259	442:445	N259	442:445	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	46	gly	glycosylation	405:417	arg2	two					401:403	two	401:403	two	401:403	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	8	47	located	detected	996:1003	arg1	1α1					958:960	collagen 1α1	949:960	collagen 1α1	949:960	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	8	47	located	detected	996:1003	arg2	hydroxylation					979:991	reduced proline hydroxylation	963:991	reduced proline hydroxylation	963:991	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	8	47	located	detected	996:1003	arg1	sites					1014:1018	eight sites	1008:1018	eight sites	1008:1018	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	0	48	theme	4-hydroxylase	43:55	arg1	subunit					57:63	prolyl 4-hydroxylase subunit	36:63	prolyl 4-hydroxylase subunit	36:63	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	1	49	dep	4-hydroxylase	233:245	arg1	α					255:255	subunit α 1	247:257	prolyl 4-hydroxylase subunit α 1 (P4HA1)	226:265	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	1	49	dep	4-hydroxylase	233:245	arg1	P4HA1					260:264	P4HA1	260:264	P4HA1	260:264	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	6	50	theme	Stt3b	684:688	arg1	Downregulation					666:679	Downregulation	666:679	Downregulation of Stt3b and Magt1	666:698	Downregulation of Stt3b and Magt1 reduces N259 glycans on P4HA1.
30919021	5	51	theme	N259	572:575	arg1	glycosylation					577:589	N259 glycosylation	572:589	N259 glycosylation on P4HA1	572:598	N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion.
30919021	1	52	theme	Ascorbic	124:131	arg1	acid					133:136	Ascorbic acid	124:136	Ascorbic acid (vitamin C, VC)	124:152	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	7	53	theme	specific	830:837	arg1	residues					847:854	five specific proline residues	825:854	five specific proline residues	825:854	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	5	54	theme	collagen	642:649	arg1	secretion					655:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	enhanced pepsin-resistant collagen 1α2 secretion	616:663	N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion.
30919021	8	55	theme	proline	1034:1040	arg1	hydroxylation					1042:1054	increased proline hydroxylation	1024:1054	increased proline hydroxylation	1024:1054	Similarly, in collagen 1α1, reduced proline hydroxylation is detected at eight sites and increased proline hydroxylation is found at four sites.
30919021	3	56	contain	has	397:399	arg1	P4HA1					391:395	P4HA1	391:395	P4HA1	391:395	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	56	contain	has	397:399	arg2	Asn					426:428	Asn	426:428	Asn (N) 113	426:436	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	56	contain	has	397:399	arg2	sites					419:423	two glycosylation sites	401:423	two glycosylation sites	401:423	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	56	contain	has	397:399	arg2	N259					442:445	N259	442:445	N259	442:445	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	5	57	from	glycosylation	577:589	arg1	P4HA1					594:598	P4HA1	594:598	P4HA1	594:598	N259 glycosylation on P4HA1 correlates with enhanced pepsin-resistant collagen 1α2 secretion.
30919021	3	58	theme	glycosylation	405:417	arg1	N259					442:445	N259	442:445	N259	442:445	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	58	theme	glycosylation	405:417	arg1	Asn					426:428	Asn	426:428	Asn (N) 113	426:436	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	3	58	theme	glycosylation	405:417	arg1	sites					419:423	two glycosylation sites	401:423	two glycosylation sites	401:423	P4HA1 has two glycosylation sites, Asn (N) 113 and N259.
30919021	7	59	theme	proline	917:923	arg1	residues					925:932	two proline residues	913:932	two proline residues	913:932	In collagen 1α2 purified from Stt3b-silenced fibroblasts, decreased hydroxylation is found at five specific proline residues, while significantly increased hydroxylation is noted at two proline residues.
30919021	4	60	theme	magnesium	520:528	arg1	transporter					530:540	magnesium transporter 1	520:542	magnesium transporter 1 (MAGT1)	520:550	Our studies show that glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1) is augmented by VC.
30919021	4	60	theme	magnesium	520:528	arg1	MAGT1					545:549	MAGT1	545:549	MAGT1	545:549	Our studies show that glycosylation of N259, but not N113, by STT3B and magnesium transporter 1 (MAGT1) is augmented by VC.
30919021	0	61	from	glycans	25:31	arg1	subunit					57:63	prolyl 4-hydroxylase subunit	36:63	prolyl 4-hydroxylase subunit	36:63	Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
30919021	1	62	theme	vitamin	139:145	arg1	VC					150:151	VC	150:151	VC	150:151	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
30919021	1	62	theme	vitamin	139:145	arg1	C					147:147	vitamin C	139:147	vitamin C	139:147	Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1).
31662433	8	0	from	case	1117:1120	arg1	pathway					1173:1179	the thiol-dependent quality control pathway	1137:1179	the thiol-dependent quality control pathway	1137:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	8	1	from	reliance	1125:1132	arg1	pathway					1173:1179	the thiol-dependent quality control pathway	1137:1179	the thiol-dependent quality control pathway	1137:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	2	2	theme	N-glycans	342:350	arg1	presence					274:281	the presence	270:281	the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans	270:350	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	0	3	theme	quality	79:85	arg1	control					87:93	thiol-dependent quality control	63:93	thiol-dependent quality control	63:93	Proper secretion of the serpin antithrombin relies strictly on thiol-dependent quality control.
31662433	4	4	theme	biochemical	509:519	arg1	labeling					469:476	metabolic labeling	459:476	metabolic labeling	459:476	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	4	theme	biochemical	509:519	arg1	model					580:584	a model	578:584	a model	578:584	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	4	theme	biochemical	509:519	arg1	assays					521:526	various biochemical assays	501:526	various biochemical assays	501:526	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	4	theme	biochemical	509:519	arg1	antithrombin					550:561	the human serpin antithrombin III	533:565	the human serpin antithrombin III (ATIII)	533:573	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	4	theme	biochemical	509:519	arg1	immunoprecipitations					479:498	immunoprecipitations	479:498	immunoprecipitations	479:498	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	2	5	theme	processed	332:340	arg1	N-glycans					342:350	processed N-glycans	332:350	processed N-glycans	332:350	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	5	6	theme	hydrophobic	679:689	arg1	core					691:694	a hydrophobic core	677:694	a hydrophobic core	677:694	Although ATIII has N-glycans and a hydrophobic core, we found that its quality control depended solely on free thiol content.
31662433	4	7	theme	various	501:507	arg1	labeling					469:476	metabolic labeling	459:476	metabolic labeling	459:476	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	7	theme	various	501:507	arg1	model					580:584	a model	578:584	a model	578:584	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	7	theme	various	501:507	arg1	assays					521:526	various biochemical assays	501:526	various biochemical assays	501:526	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	7	theme	various	501:507	arg1	antithrombin					550:561	the human serpin antithrombin III	533:565	the human serpin antithrombin III (ATIII)	533:573	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	7	theme	various	501:507	arg1	immunoprecipitations					479:498	immunoprecipitations	479:498	immunoprecipitations	479:498	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	2	8	theme	exposed	286:292	arg1	surfaces					306:313	exposed hydrophobic surfaces	286:313	exposed hydrophobic surfaces	286:313	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	8	9	theme	fundamental	1078:1088	arg1	vulnerability					1090:1102	a fundamental vulnerability	1076:1102	a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway	1076:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	4	10	theme	metabolic	459:467	arg1	labeling					469:476	metabolic labeling	459:476	metabolic labeling	459:476	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	10	theme	metabolic	459:467	arg1	model					580:584	a model	578:584	a model	578:584	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	10	theme	metabolic	459:467	arg1	assays					521:526	various biochemical assays	501:526	various biochemical assays	501:526	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	10	theme	metabolic	459:467	arg1	antithrombin					550:561	the human serpin antithrombin III	533:565	the human serpin antithrombin III (ATIII)	533:573	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	10	theme	metabolic	459:467	arg1	immunoprecipitations					479:498	immunoprecipitations	479:498	immunoprecipitations	479:498	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	8	11	theme	ERQC	1107:1110	arg1	vulnerability					1090:1102	a fundamental vulnerability	1076:1102	a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway	1076:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	4	12	theme	mammalian	627:635	arg1	cells					637:641	mammalian cells	627:641	mammalian cells	627:641	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	13	theme	systems	616:622	arg1	role					603:606	the role	599:606	the role of ERQC systems in mammalian cells	599:641	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	5	14	theme	thiol	755:759	arg1	content					761:767	free thiol content	750:767	free thiol content	750:767	Although ATIII has N-glycans and a hydrophobic core, we found that its quality control depended solely on free thiol content.
31662433	4	15	theme	ERQC	611:614	arg1	systems					616:622	ERQC systems	611:622	ERQC systems	611:622	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	5	16	theme	free	750:753	arg1	content					761:767	free thiol content	750:767	free thiol content	750:767	Although ATIII has N-glycans and a hydrophobic core, we found that its quality control depended solely on free thiol content.
31662433	5	17	theme	quality	715:721	arg1	control					723:729	its quality control	711:729	its quality control	711:729	Although ATIII has N-glycans and a hydrophobic core, we found that its quality control depended solely on free thiol content.
31662433	3	18	theme	given	409:413	arg1	substrate					415:423	a given substrate	407:423	a given substrate	407:423	How these features dictate which ERQC pathways engage a given substrate is poorly understood.
31662433	0	19	theme	Proper	0:5	arg1	secretion					7:15	Proper secretion	0:15	Proper secretion of the serpin antithrombin	0:42	Proper secretion of the serpin antithrombin relies strictly on thiol-dependent quality control.
31662433	4	20	theme	serpin	543:548	arg1	antithrombin					550:561	the human serpin antithrombin III	533:565	the human serpin antithrombin III (ATIII)	533:573	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	20	theme	serpin	543:548	arg1	labeling					469:476	metabolic labeling	459:476	metabolic labeling	459:476	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	20	theme	serpin	543:548	arg1	model					580:584	a model	578:584	a model	578:584	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	20	theme	serpin	543:548	arg1	assays					521:526	various biochemical assays	501:526	various biochemical assays	501:526	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	20	theme	serpin	543:548	arg1	ATIII					568:572	ATIII	568:572	ATIII	568:572	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	20	theme	serpin	543:548	arg1	immunoprecipitations					479:498	immunoprecipitations	479:498	immunoprecipitations	479:498	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	8	21	theme	control	1165:1171	arg1	pathway					1173:1179	the thiol-dependent quality control pathway	1137:1179	the thiol-dependent quality control pathway	1137:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	2	22	theme	surfaces	306:313	arg1	presence					274:281	the presence	270:281	the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans	270:350	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	1	23	theme	client	183:188	arg1	proteins					190:197	client proteins	183:197	client proteins	183:197	The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded.
31662433	4	24	theme	human	537:541	arg1	antithrombin					550:561	the human serpin antithrombin III	533:565	the human serpin antithrombin III (ATIII)	533:573	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	24	theme	human	537:541	arg1	labeling					469:476	metabolic labeling	459:476	metabolic labeling	459:476	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	24	theme	human	537:541	arg1	model					580:584	a model	578:584	a model	578:584	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	24	theme	human	537:541	arg1	assays					521:526	various biochemical assays	501:526	various biochemical assays	501:526	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	24	theme	human	537:541	arg1	ATIII					568:572	ATIII	568:572	ATIII	568:572	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	4	24	theme	human	537:541	arg1	immunoprecipitations					479:498	immunoprecipitations	479:498	immunoprecipitations	479:498	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	2	25	theme	hydrophobic	294:304	arg1	surfaces					306:313	exposed hydrophobic surfaces	286:313	exposed hydrophobic surfaces	286:313	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	4	26	from	role	603:606	arg1	cells					637:641	mammalian cells	627:641	mammalian cells	627:641	Here, using metabolic labeling, immunoprecipitations, various biochemical assays, and the human serpin antithrombin III (ATIII) as a model, we explored the role of ERQC systems in mammalian cells.
31662433	1	27	theme	quality	108:114	arg1	machinery					124:132	The protein quality control machinery	96:132	The protein quality control machinery of the endoplasmic reticulum (ERQC)	96:168	The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded.
31662433	0	28	theme	antithrombin	31:42	arg1	secretion					7:15	Proper secretion	0:15	Proper secretion of the serpin antithrombin	0:42	Proper secretion of the serpin antithrombin relies strictly on thiol-dependent quality control.
31662433	5	29	contain	has	659:661	arg2	N-glycans					663:671	N-glycans	663:671	N-glycans	663:671	Although ATIII has N-glycans and a hydrophobic core, we found that its quality control depended solely on free thiol content.
31662433	5	29	contain	has	659:661	arg1	ATIII					653:657	ATIII	653:657	ATIII	653:657	Although ATIII has N-glycans and a hydrophobic core, we found that its quality control depended solely on free thiol content.
31662433	5	29	contain	has	659:661	arg2	core					691:694	a hydrophobic core	677:694	a hydrophobic core	677:694	Although ATIII has N-glycans and a hydrophobic core, we found that its quality control depended solely on free thiol content.
31662433	0	30	theme	serpin	24:29	arg1	antithrombin					31:42	the serpin antithrombin	20:42	the serpin antithrombin	20:42	Proper secretion of the serpin antithrombin relies strictly on thiol-dependent quality control.
31662433	6	31	from	Mutagenesis	770:780	arg1	ATIII					809:813	ATIII	809:813	ATIII	809:813	Mutagenesis of all six Cys residues in ATIII to Ala resulted in its efficient secretion even though the product was not natively folded.
31662433	6	32	theme	residues	797:804	arg1	Mutagenesis					770:780	Mutagenesis	770:780	Mutagenesis of all six Cys residues in ATIII to Ala	770:820	Mutagenesis of all six Cys residues in ATIII to Ala resulted in its efficient secretion even though the product was not natively folded.
31662433	3	33	theme	ERQC	386:389	arg1	pathways					391:398	pathways	391:398	pathways	391:398	How these features dictate which ERQC pathways engage a given substrate is poorly understood.
31662433	8	34	theme	reliance	1125:1132	arg1	case					1117:1120	a case	1115:1120	a case of reliance on the thiol-dependent quality control pathway	1115:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	6	35	theme	Cys	793:795	arg1	residues					797:804	all six Cys residues	785:804	all six Cys residues	785:804	Mutagenesis of all six Cys residues in ATIII to Ala resulted in its efficient secretion even though the product was not natively folded.
31662433	2	36	theme	ERQC	220:223	arg1	substrates					225:234	ERQC substrates	220:234	ERQC substrates	220:234	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	2	36	theme	ERQC	220:223	arg1	nonnative					257:265	nonnative	257:265	nonnative	257:265	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	8	37	from	pathway	1173:1179	arg1	case					1117:1120	a case	1115:1120	a case of reliance on the thiol-dependent quality control pathway	1115:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	1	38	theme	control	116:122	arg1	machinery					124:132	The protein quality control machinery	96:132	The protein quality control machinery of the endoplasmic reticulum (ERQC)	96:168	The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded.
31662433	6	39	theme	efficient	838:846	arg1	secretion					848:856	its efficient secretion	834:856	its efficient secretion	834:856	Mutagenesis of all six Cys residues in ATIII to Ala resulted in its efficient secretion even though the product was not natively folded.
31662433	8	40	theme	ERQC	1052:1055	arg1	systems					1057:1063	ERQC systems	1052:1063	ERQC systems	1052:1063	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	2	41	theme	thiols	321:326	arg1	presence					274:281	the presence	270:281	the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans	270:350	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	1	42	theme	protein	100:106	arg1	machinery					124:132	The protein quality control machinery	96:132	The protein quality control machinery of the endoplasmic reticulum (ERQC)	96:168	The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded.
31662433	7	43	theme	endoplasmic	960:970	arg1	reticulum					972:980	the endoplasmic reticulum	956:980	the endoplasmic reticulum	956:980	ATIII variants with free thiols were retained in the endoplasmic reticulum but not degraded.
31662433	8	44	from	vulnerability	1090:1102	arg1	case					1117:1120	a case	1115:1120	a case of reliance on the thiol-dependent quality control pathway	1115:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	2	45	theme	free	316:319	arg1	thiols					321:326	free thiols	316:326	free thiols	316:326	ERQC substrates may be recognized as nonnative by the presence of exposed hydrophobic surfaces, free thiols, or processed N-glycans.
31662433	8	46	theme	thiol-dependent	1141:1155	arg1	pathway					1173:1179	the thiol-dependent quality control pathway	1137:1179	the thiol-dependent quality control pathway	1137:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	7	47	with	variants	913:920	arg1	thiols					932:937	free thiols	927:937	free thiols	927:937	ATIII variants with free thiols were retained in the endoplasmic reticulum but not degraded.
31662433	0	48	theme	thiol-dependent	63:77	arg1	control					87:93	thiol-dependent quality control	63:93	thiol-dependent quality control	63:93	Proper secretion of the serpin antithrombin relies strictly on thiol-dependent quality control.
31662433	7	49	theme	free	927:930	arg1	thiols					932:937	free thiols	927:937	free thiols	927:937	ATIII variants with free thiols were retained in the endoplasmic reticulum but not degraded.
31662433	1	50	theme	endoplasmic	141:151	arg1	reticulum					153:161	the endoplasmic reticulum	137:161	the endoplasmic reticulum (ERQC)	137:168	The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded.
31662433	1	50	theme	endoplasmic	141:151	arg1	ERQC					164:167	ERQC	164:167	ERQC	164:167	The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded.
31662433	8	51	theme	quality	1157:1163	arg1	pathway					1173:1179	the thiol-dependent quality control pathway	1137:1179	the thiol-dependent quality control pathway	1137:1179	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	8	52	theme	systems	1057:1063	arg1	hierarchy					1039:1047	the hierarchy	1035:1047	the hierarchy of ERQC systems	1035:1063	These results provide insight into the hierarchy of ERQC systems and reveal a fundamental vulnerability of ERQC in a case of reliance on the thiol-dependent quality control pathway.
31662433	7	53	theme	ATIII	907:911	arg1	variants					913:920	ATIII variants	907:920	ATIII variants with free thiols	907:937	ATIII variants with free thiols were retained in the endoplasmic reticulum but not degraded.
31662433	1	54	theme	reticulum	153:161	arg1	machinery					124:132	The protein quality control machinery	96:132	The protein quality control machinery of the endoplasmic reticulum (ERQC)	96:168	The protein quality control machinery of the endoplasmic reticulum (ERQC) ensures that client proteins are properly folded.
30801341	6	0	theme	inflammatory	1414:1425	arg1	response					1427:1434	the inflammatory response	1410:1434	the inflammatory response in keloids	1410:1445	We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids.
30801341	0	1	from	Galectin-3	15:24	arg1	Thickening					77:86	the Dermal Thickening	66:86	the Dermal Thickening of Keloid Tissues	66:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	7	2	theme	endothelial	1603:1613	arg1	fibroblasts					1576:1586	fibroblasts	1576:1586	fibroblasts	1576:1586	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	7	2	theme	endothelial	1603:1613	arg1	cells					1615:1619	endothelial cells	1603:1619	endothelial cells	1603:1619	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	5	3	from	cytoplasm	1162:1170	arg1	present					1147:1153	present	1147:1153	present	1147:1153	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	1	4	theme	inflammatory	153:164	arg1	number					261:266	increased number	251:266	increased number of proinflammatory immune cells as well as uncontrolled cell proliferation	251:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	4	theme	inflammatory	153:164	arg1	deposition					377:386	exacerbated and disorganized deposition	348:386	exacerbated and disorganized deposition of extracellular matrix (ECM) molecules	348:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	4	theme	inflammatory	153:164	arg1	Keloids					107:113	Keloids	107:113	Keloids	107:113	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	4	theme	inflammatory	153:164	arg1	vascularization					234:248	abnormal vascularization	225:248	abnormal vascularization	225:248	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	4	theme	inflammatory	153:164	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	0	5	from	Partners	54:61	arg1	Thickening					77:86	the Dermal Thickening	66:86	the Dermal Thickening of Keloid Tissues	66:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	1	6	theme	proinflammatory	271:285	arg1	cells					294:298	proinflammatory immune cells	271:298	proinflammatory immune cells as well as uncontrolled cell proliferation	271:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	0	7	theme	Dermal	70:75	arg1	Thickening					77:86	the Dermal Thickening	66:86	the Dermal Thickening of Keloid Tissues	66:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	7	8	theme	immune	1589:1594	arg1	fibroblasts					1576:1586	fibroblasts	1576:1586	fibroblasts	1576:1586	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	7	8	theme	immune	1589:1594	arg1	cells					1596:1600	immune cells	1589:1600	immune cells	1589:1600	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	5	9	located	present	1147:1153	arg1	cytoplasm					1162:1170	the cytoplasm	1158:1170	the cytoplasm	1158:1170	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	9	located	present	1147:1153	arg2	Gal-1					1126:1130	Gal-1	1126:1130	Gal-1	1126:1130	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	9	located	present	1147:1153	arg2	Gal-3					1136:1140	Gal-3	1136:1140	Gal-3	1136:1140	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	1	10	theme	immune	287:292	arg1	cells					294:298	proinflammatory immune cells	271:298	proinflammatory immune cells as well as uncontrolled cell proliferation	271:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	0	11	theme	Keloid	91:96	arg1	Tissues					98:104	Keloid Tissues	91:104	Keloid Tissues	91:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	0	12	from	Galectin-1	0:9	arg1	Thickening					77:86	the Dermal Thickening	66:86	the Dermal Thickening of Keloid Tissues	66:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	5	13	theme	cell	1186:1189	arg1	membrane					1191:1198	the cell membrane	1182:1198	the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening	1182:1276	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	14	theme	thickening	1267:1276	arg1	cells					1247:1251	immune and endothelial cells	1224:1251	immune and endothelial cells of the dermal thickening	1224:1276	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	14	theme	thickening	1267:1276	arg1	fibroblasts					1208:1218	some fibroblasts	1203:1218	some fibroblasts	1203:1218	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	1	15	theme	cells	294:298	arg1	deposition					377:386	exacerbated and disorganized deposition	348:386	exacerbated and disorganized deposition of extracellular matrix (ECM) molecules	348:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	15	theme	cells	294:298	arg1	number					261:266	increased number	251:266	increased number of proinflammatory immune cells as well as uncontrolled cell proliferation	251:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	15	theme	cells	294:298	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	15	theme	cells	294:298	arg1	vascularization					234:248	abnormal vascularization	225:248	abnormal vascularization	225:248	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	16	theme	extracellular	391:403	arg1	matrix					405:410	extracellular matrix	391:410	extracellular matrix (ECM) molecules	391:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	16	theme	extracellular	391:403	arg1	ECM					413:415	ECM	413:415	ECM	413:415	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	7	17	theme	fibroblast	1678:1687	arg1	morphology					1689:1698	the fibroblast morphology	1674:1698	the fibroblast morphology	1674:1698	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	4	18	from	infiltrate	1008:1017	arg1	cells					1101:1105	some immune cells	1089:1105	some immune cells	1089:1105	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	3	19	with	interactions	675:686	arg1	partners					715:722	their binding partners	701:722	their binding partners in keloid tissues	701:740	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	3	19	with	interactions	675:686	arg1	some					693:696	some	693:696	some	693:696	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	1	20	theme	matrix	405:410	arg1	molecules					418:426	extracellular matrix (ECM) molecules	391:426	extracellular matrix (ECM) molecules	391:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	4	21	theme	cell	1003:1006	arg1	infiltrate					1008:1017	the immune cell infiltrate	992:1017	the immune cell infiltrate	992:1017	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	4	21	theme	cell	1003:1006	arg1	fibroblasts					961:971	the elongated fibroblasts	947:971	the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells	947:1105	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	7	22	theme	supramolecular	1528:1541	arg1	structure					1543:1551	a supramolecular structure	1526:1551	a supramolecular structure	1526:1551	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	5	23	theme	dermal	1260:1265	arg1	thickening					1267:1276	the dermal thickening	1256:1276	the dermal thickening	1256:1276	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	0	24	theme	Tissues	98:104	arg1	Thickening					77:86	the Dermal Thickening	66:86	the Dermal Thickening of Keloid Tissues	66:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	3	25	theme	binding	707:713	arg1	partners					715:722	their binding partners	701:722	their binding partners in keloid tissues	701:740	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	4	26	theme	keloids	815:821	arg1	thickening					801:810	the dermal thickening	790:810	the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin	790:921	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	2	27	link	O-linked	485:492	arg1	residues					501:508	O-linked glycan residues	485:508	O-linked glycan residues	485:508	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	7	28	theme	binding	1500:1506	arg1	partners					1508:1515	their binding partners	1494:1515	their binding partners	1494:1515	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	4	29	theme	immune	1094:1099	arg1	cells					1101:1105	some immune cells	1089:1105	some immune cells	1089:1105	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	6	30	with	concert	1315:1321	arg1	some					1328:1331	some	1328:1331	some	1328:1331	We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids.
30801341	6	30	with	concert	1315:1321	arg1	molecules					1344:1352	the ECM molecules	1336:1352	the ECM molecules produced by fibroblasts and by immune cells	1336:1396	We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids.
30801341	3	31	theme	keloid	727:732	arg1	tissues					734:740	keloid tissues	727:740	keloid tissues	727:740	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	1	32	theme	disorganized	364:375	arg1	deposition					377:386	exacerbated and disorganized deposition	348:386	exacerbated and disorganized deposition of extracellular matrix (ECM) molecules	348:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	32	theme	disorganized	364:375	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	3	33	from	partners	715:722	arg1	tissues					734:740	keloid tissues	727:740	keloid tissues	727:740	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	4	34	attach	attached	1020:1027	arg1	bundles					1041:1047	collagen bundles	1032:1047	collagen bundles	1032:1047	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	4	34	attach	attached	1020:1027	arg2	fibroblasts					961:971	the elongated fibroblasts	947:971	the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells	947:1105	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	4	34	attach	attached	1020:1027	arg2	infiltrate					1008:1017	the immune cell infiltrate	992:1017	the immune cell infiltrate	992:1017	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	3	35	with	Gal-1	644:648	arg1	partners					715:722	their binding partners	701:722	their binding partners in keloid tissues	701:740	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	3	35	with	Gal-1	644:648	arg1	some					693:696	some	693:696	some	693:696	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	1	36	theme	numerous	203:210	arg1	fibroblasts					212:222	numerous fibroblasts	203:222	numerous fibroblasts	203:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	2	37	theme	molecules	460:468	arg1	many					442:445	many	442:445	many	442:445	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	2	37	theme	molecules	460:468	arg1	molecules					460:468	these ECM molecules	450:468	these ECM molecules	450:468	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	2	37	theme	molecules	460:468	arg1	targets					542:548	potential targets	532:548	potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3)	532:594	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	5	38	from	present	1147:1153	arg1	cytoplasm					1162:1170	the cytoplasm	1158:1170	the cytoplasm	1158:1170	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	39	theme	endothelial	1235:1245	arg1	cells					1247:1251	immune and endothelial cells	1224:1251	immune and endothelial cells of the dermal thickening	1224:1276	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	3	40	dep	presence	615:622	arg1	the					611:613	the	611:613	the	611:613	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	2	41	theme	ECM	456:458	arg1	molecules					460:468	these ECM molecules	450:468	these ECM molecules	450:468	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	1	42	theme	uncontrolled	311:322	arg1	proliferation					329:341	uncontrolled cell proliferation	311:341	proinflammatory immune cells as well as uncontrolled cell proliferation	271:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	7	43	theme	cell	1560:1563	arg1	surface					1565:1571	the cell surface	1556:1571	the cell surface of fibroblasts, immune cells, endothelial cells	1556:1619	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	3	44	theme	Gal-3	654:658	arg1	localization					628:639	localization	628:639	localization	628:639	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	3	44	theme	Gal-3	654:658	arg1	presence					615:622	presence	615:622	presence	615:622	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	6	45	from	response	1427:1434	arg1	keloids					1439:1445	keloids	1439:1445	keloids	1439:1445	We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids.
30801341	3	46	with	Gal-3	654:658	arg1	partners					715:722	their binding partners	701:722	their binding partners in keloid tissues	701:740	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	3	46	with	Gal-3	654:658	arg1	some					693:696	some	693:696	some	693:696	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	0	47	theme	Potential	36:44	arg1	Partners					54:61	Their Potential Binding Partners	30:61	Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues	30:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	1	48	theme	cell	324:327	arg1	proliferation					329:341	uncontrolled cell proliferation	311:341	proinflammatory immune cells as well as uncontrolled cell proliferation	271:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	4	49	theme	integrin	895:902	arg1	β1					904:905	integrin β1	895:905	integrin β1	895:905	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	4	49	theme	integrin	895:902	arg1	keloids					815:821	keloids	815:821	keloids	815:821	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	1	50	theme	molecules	418:426	arg1	deposition					377:386	exacerbated and disorganized deposition	348:386	exacerbated and disorganized deposition of extracellular matrix (ECM) molecules	348:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	50	theme	molecules	418:426	arg1	number					261:266	increased number	251:266	increased number of proinflammatory immune cells as well as uncontrolled cell proliferation	251:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	50	theme	molecules	418:426	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	50	theme	molecules	418:426	arg1	vascularization					234:248	abnormal vascularization	225:248	abnormal vascularization	225:248	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	4	51	theme	dermal	794:799	arg1	thickening					801:810	the dermal thickening	790:810	the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin	790:921	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	6	52	theme	immune	1385:1390	arg1	cells					1392:1396	immune cells	1385:1396	immune cells	1385:1396	We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids.
30801341	1	53	theme	abnormal	225:232	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	53	theme	abnormal	225:232	arg1	vascularization					234:248	abnormal vascularization	225:248	abnormal vascularization	225:248	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	2	54	theme	glycan	494:499	arg1	residues					501:508	O-linked glycan residues	485:508	O-linked glycan residues	485:508	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	1	55	theme	proliferation	329:341	arg1	deposition					377:386	exacerbated and disorganized deposition	348:386	exacerbated and disorganized deposition of extracellular matrix (ECM) molecules	348:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	55	theme	proliferation	329:341	arg1	number					261:266	increased number	251:266	increased number of proinflammatory immune cells as well as uncontrolled cell proliferation	251:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	55	theme	proliferation	329:341	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	55	theme	proliferation	329:341	arg1	vascularization					234:248	abnormal vascularization	225:248	abnormal vascularization	225:248	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	4	56	theme	elongated	951:959	arg1	fibroblasts					961:971	the elongated fibroblasts	947:971	the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells	947:1105	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	4	56	theme	elongated	951:959	arg1	infiltrate					1008:1017	the immune cell infiltrate	992:1017	the immune cell infiltrate	992:1017	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	3	57	theme	Gal-1	644:648	arg1	localization					628:639	localization	628:639	localization	628:639	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	3	57	theme	Gal-1	644:648	arg1	presence					615:622	presence	615:622	presence	615:622	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	4	58	theme	immune	996:1001	arg1	infiltrate					1008:1017	the immune cell infiltrate	992:1017	the immune cell infiltrate	992:1017	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	4	58	theme	immune	996:1001	arg1	fibroblasts					961:971	the elongated fibroblasts	947:971	the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells	947:1105	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	2	59	theme	potential	532:540	arg1	targets					542:548	potential targets	532:548	potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3)	532:594	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	2	59	theme	potential	532:540	arg1	molecules					460:468	these ECM molecules	450:468	these ECM molecules	450:468	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	2	59	theme	potential	532:540	arg1	many					442:445	many	442:445	many	442:445	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	2	60	theme	O-linked	485:492	arg1	residues					501:508	O-linked glycan residues	485:508	O-linked glycan residues	485:508	Importantly, many of these ECM molecules display N- and O-linked glycan residues and are considered as potential targets for galectin-1 (Gal-1) and galectin-3 (Gal-3).
30801341	0	61	theme	Binding	46:52	arg1	Partners					54:61	Their Potential Binding Partners	30:61	Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues	30:104	Galectin-1 and Galectin-3 and Their Potential Binding Partners in the Dermal Thickening of Keloid Tissues.
30801341	7	62	theme	inflammatory	1765:1776	arg1	responses					1778:1786	the inflammatory responses	1761:1786	the inflammatory responses	1761:1786	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	4	63	theme	collagen	1032:1039	arg1	bundles					1041:1047	collagen bundles	1032:1047	collagen bundles	1032:1047	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	1	64	theme	exacerbated	348:358	arg1	deposition					377:386	exacerbated and disorganized deposition	348:386	exacerbated and disorganized deposition of extracellular matrix (ECM) molecules	348:426	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	64	theme	exacerbated	348:358	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	3	65	theme	interactions	675:686	arg1	localization					628:639	localization	628:639	localization	628:639	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	3	65	theme	interactions	675:686	arg1	presence					615:622	presence	615:622	presence	615:622	Nevertheless, the presence and localization of Gal-1 and Gal-3 as well as the interactions with some of their binding partners in keloid tissues have not been considered.
30801341	7	66	theme	extracellular	1633:1645	arg1	space					1647:1651	the extracellular space	1629:1651	the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses	1629:1786	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	5	67	theme	fibroblasts	1208:1218	arg1	membrane					1191:1198	the cell membrane	1182:1198	the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening	1182:1276	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	4	68	theme	tenascin	877:884	arg1	keloids					815:821	keloids	815:821	keloids	815:821	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	4	68	theme	tenascin	877:884	arg1	C					886:886	tenascin C	877:886	tenascin C	877:886	Here, we show that in the dermal thickening of keloids, versican, syndecan-1, fibronectin, thrombospondin-1, tenascin C, CD44, integrin β1, and N-cadherin were immunolocalized in the elongated fibroblasts that were close to the immune cell infiltrate, attached to collagen bundles, and around the microvasculature and in some immune cells.
30801341	7	69	theme	fibroblasts	1576:1586	arg1	surface					1565:1571	the cell surface	1556:1571	the cell surface of fibroblasts, immune cells, endothelial cells	1556:1619	We also proposed that Gal-1 and Gal-3 through their binding partners may form a supramolecular structure at the cell surface of fibroblasts, immune cells, endothelial cells, and in the extracellular space that might influence the fibroblast morphology, adhesion, proliferation, migration, and survival as well as the inflammatory responses.
30801341	1	70	theme	increased	251:259	arg1	number					261:266	increased number	251:266	increased number of proinflammatory immune cells as well as uncontrolled cell proliferation	251:341	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	1	70	theme	increased	251:259	arg1	disorder					166:173	an inflammatory disorder	150:173	an inflammatory disorder characterized by exhibiting numerous fibroblasts	150:222	Keloids are defined histopathologically as an inflammatory disorder characterized by exhibiting numerous fibroblasts, abnormal vascularization, increased number of proinflammatory immune cells as well as uncontrolled cell proliferation, and exacerbated and disorganized deposition of extracellular matrix (ECM) molecules.
30801341	6	71	theme	ECM	1340:1342	arg1	molecules					1344:1352	the ECM molecules	1336:1352	the ECM molecules produced by fibroblasts and by immune cells	1336:1396	We suggest that Gal-1 and Gal-3, in concert with some of the ECM molecules produced by fibroblasts and by immune cells, counteract the inflammatory response in keloids.
30801341	5	72	theme	immune	1224:1229	arg1	cells					1247:1251	immune and endothelial cells	1224:1251	immune and endothelial cells of the dermal thickening	1224:1276	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	73	attach	present	1147:1153	arg1	cytoplasm					1162:1170	the cytoplasm	1158:1170	the cytoplasm	1158:1170	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	73	attach	present	1147:1153	arg2	Gal-1					1126:1130	Gal-1	1126:1130	Gal-1	1126:1130	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	73	attach	present	1147:1153	arg2	Gal-3					1136:1140	Gal-3	1136:1140	Gal-3	1136:1140	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
30801341	5	74	theme	cells	1247:1251	arg1	membrane					1191:1198	the cell membrane	1182:1198	the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening	1182:1276	We also show that Gal-1 and Gal-3 were present in the cytoplasm and along the cell membrane of some fibroblasts and immune and endothelial cells of the dermal thickening.
31300553	4	0	theme	βOGTKO	940:945	arg1	mice					947:950	βOGTKO mice	940:950	βOGTKO mice	940:950	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	6	1	theme	OGT	1166:1168	arg1	loss					1170:1173	OGT loss	1166:1173	OGT loss	1166:1173	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	2	2	theme	nutrient-sensing	384:399	arg1	protein					401:407	the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO)	380:445	the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO)	380:445	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	4	3	theme	Click	662:666	arg1	labeling					677:684	Click O-GlcNAc labeling	662:684	Click O-GlcNAc labeling	662:684	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	3	4	theme	latter	566:571	arg1	defect					573:578	this latter defect	561:578	this latter defect	561:578	The mechanisms underlying this latter defect are unknown.
31300553	4	5	theme	-dependent	904:913	arg1	processing					926:935	carboxypeptidase E (CPE)-dependent proinsulin processing	880:935	carboxypeptidase E (CPE)-dependent proinsulin processing	880:935	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	6	6	theme	genetic	1235:1241	arg1	reconstitution					1243:1256	genetic reconstitution	1235:1256	genetic reconstitution of CPE in βOGTKO islets	1235:1280	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	8	7	from	Ser-61	1673:1678	arg1	eIF4G1					1663:1668	eIF4G1	1663:1668	eIF4G1	1663:1668	Furthermore, our results reveal that OGT O-GlcNAc-modifies eIF4G1 at Ser-61 and that this modification is critical for eIF4G1 protein stability.
31300553	7	8	theme	islet	1525:1529	arg1	levels					1535:1540	islet CPE levels	1525:1540	islet CPE levels	1525:1540	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	4	9	theme	processing	926:935	arg1	O-GlcNAcylation					803:817	the O-GlcNAcylation	799:817	the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice	799:950	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	10	theme	initiation	845:854	arg1	eIF4G1					868:873	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	9	11	theme	direct	1784:1789	arg1	link					1791:1794	a direct link	1782:1794	a direct link between nutrient-sensitive OGT and insulin processing	1782:1848	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	6	12	theme	β-cell-resident	1210:1224	arg1	CPE					1226:1228	β-cell-resident CPE	1210:1228	β-cell-resident CPE	1210:1228	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	2	13	theme	nutrient	333:340	arg1	flux					342:345	nutrient flux	333:345	nutrient flux	333:345	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	1	14	theme	processing	221:230	arg1	failure					188:194	a failure	186:194	a failure	186:194	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	1	14	theme	processing	221:230	arg1	hallmark					155:162	An early hallmark	146:162	An early hallmark of type 2 diabetes	146:181	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	6	15	theme	proinsulin-to-insulin	1308:1328	arg1	ratio					1330:1334	the dysfunctional proinsulin-to-insulin ratio	1290:1334	the dysfunctional proinsulin-to-insulin ratio	1290:1334	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	1	16	theme	pancreatic	235:244	arg1	β-cells					246:252	pancreatic β-cells	235:252	pancreatic β-cells	235:252	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	7	17	theme	target	1443:1448	arg1	eIF4G1					1450:1455	the suspected OGT target eIF4G1	1425:1455	the suspected OGT target eIF4G1	1425:1455	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	9	18	theme	insulin	1831:1837	arg1	processing					1839:1848	insulin processing	1831:1848	insulin processing	1831:1848	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	7	19	theme	suspected	1429:1437	arg1	eIF4G1					1450:1455	the suspected OGT target eIF4G1	1425:1455	the suspected OGT target eIF4G1	1425:1455	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	5	20	theme	-mediated	1132:1140	arg1	status					1149:1154	-mediated stress status	1132:1154	-mediated stress status	1132:1154	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	2	21	theme	Proinsulin	289:298	arg1	processing					300:309	Proinsulin processing	289:309	Proinsulin processing	289:309	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	1	22	from	failure	188:194	arg1	β-cells					246:252	pancreatic β-cells	235:252	pancreatic β-cells	235:252	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	8	23	theme	protein	1730:1736	arg1	stability					1738:1746	eIF4G1 protein stability	1723:1746	eIF4G1 protein stability	1723:1746	Furthermore, our results reveal that OGT O-GlcNAc-modifies eIF4G1 at Ser-61 and that this modification is critical for eIF4G1 protein stability.
31300553	1	24	theme	type	167:170	arg1	diabetes					174:181	type 2 diabetes	167:181	type 2 diabetes	167:181	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	7	25	from	translation	1491:1501	arg1	β-cells					1506:1512	β-cells	1506:1512	β-cells	1506:1512	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	1	26	theme	diabetes	174:181	arg1	failure					188:194	a failure	186:194	a failure	186:194	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	1	26	theme	diabetes	174:181	arg1	hallmark					155:162	An early hallmark	146:162	An early hallmark of type 2 diabetes	146:181	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	0	27	from	eIF4G1	0:5	arg1	β-cells					94:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	2	28	dep	protein	401:407	arg1	βOGTKO					439:444	βOGTKO	439:444	βOGTKO	439:444	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	2	28	dep	protein	401:407	arg1	transferase					426:436	modifier OGlcNAc transferase	409:436	the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO)	380:445	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	6	29	theme	βOGTKO	1268:1273	arg1	islets					1275:1280	βOGTKO islets	1268:1280	βOGTKO islets	1268:1280	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	5	30	theme	glucose	1034:1040	arg1	levels					1042:1047	glucose levels	1034:1047	glucose levels	1034:1047	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	9	31	theme	O-GlcNAc	1901:1908	arg1	modification					1910:1921	post-translational O-GlcNAc modification	1882:1921	post-translational O-GlcNAc modification	1882:1921	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	4	32	theme	4γ1	863:865	arg1	eIF4G1					868:873	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	2	33	theme	early	493:497	arg1	development					499:509	early development	493:509	early development of hyperproinsulinemia	493:532	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	6	34	from	reconstitution	1243:1256	arg1	islets					1275:1280	βOGTKO islets	1268:1280	βOGTKO islets	1268:1280	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	4	35	from	O-GlcNAcylation	803:817	arg1	mice					947:950	βOGTKO mice	940:950	βOGTKO mice	940:950	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	5	36	theme	age	1024:1026	arg1	independent					1009:1019	independent	1009:1019	independent	1009:1019	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	9	37	theme	cell	1934:1937	arg1	physiology					1939:1948	general cell physiology	1926:1948	general cell physiology	1926:1948	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	4	38	theme	several	605:611	arg1	immunofluorescence					707:724	immunofluorescence	707:724	immunofluorescence	707:724	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	38	theme	several	605:611	arg1	approaches					613:622	several approaches	605:622	several approaches	605:622	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	38	theme	several	605:611	arg1	immunoblotting					687:700	immunoblotting	687:700	immunoblotting	687:700	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	38	theme	several	605:611	arg1	mutagenesis					649:659	site-directed mutagenesis	635:659	site-directed mutagenesis	635:659	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	38	theme	several	605:611	arg1	labeling					677:684	Click O-GlcNAc labeling	662:684	Click O-GlcNAc labeling	662:684	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	39	theme	eukaryotic	822:831	arg1	eIF4G1					868:873	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	0	40	theme	carboxypeptidase	11:26	arg1	E					28:28	carboxypeptidase E	11:28	carboxypeptidase E	11:28	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	5	41	theme	sex	1029:1031	arg1	independent					1009:1019	independent	1009:1019	independent	1009:1019	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	8	42	theme	OGT	1641:1643	arg1	O-GlcNAc-modifies					1645:1661	OGT O-GlcNAc-modifies	1641:1661	OGT O-GlcNAc-modifies	1641:1661	Furthermore, our results reveal that OGT O-GlcNAc-modifies eIF4G1 at Ser-61 and that this modification is critical for eIF4G1 protein stability.
31300553	2	43	theme	β-cell	454:459	arg1	failure					461:467	β-cell failure	454:467	β-cell failure	454:467	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	0	44	theme	axis	30:33	arg1	dysregulation					35:47	axis dysregulation	30:47	axis dysregulation	30:47	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	5	45	theme	homologous	1107:1116	arg1	CHOP					1127:1130	CHOP	1127:1130	CHOP	1127:1130	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	5	45	theme	homologous	1107:1116	arg1	protein					1118:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein	1054:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)	1054:1131	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	0	46	theme	transferase-deficient	61:81	arg1	β-cells					94:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	4	47	theme	eIF4G1	868:873	arg1	O-GlcNAcylation					803:817	the O-GlcNAcylation	799:817	the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice	799:950	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	7	48	theme	βOGTKO	1562:1567	arg1	hyperproinsulinemia					1583:1601	βOGTKO islet-induced hyperproinsulinemia	1562:1601	βOGTKO islet-induced hyperproinsulinemia	1562:1601	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	5	49	theme	endoplasmic	1054:1064	arg1	CHOP					1127:1130	CHOP	1127:1130	CHOP	1127:1130	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	5	49	theme	endoplasmic	1054:1064	arg1	protein					1118:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein	1054:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)	1054:1131	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	4	50	theme	O-GlcNAc	668:675	arg1	labeling					677:684	Click O-GlcNAc labeling	662:684	Click O-GlcNAc labeling	662:684	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	2	51	theme	OGlcNAc	418:424	arg1	βOGTKO					439:444	βOGTKO	439:444	βOGTKO	439:444	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	2	51	theme	OGlcNAc	418:424	arg1	transferase					426:436	modifier OGlcNAc transferase	409:436	the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO)	380:445	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	5	52	theme	enhancer-binding	1082:1097	arg1	CHOP					1127:1130	CHOP	1127:1130	CHOP	1127:1130	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	5	52	theme	enhancer-binding	1082:1097	arg1	protein					1118:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein	1054:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)	1054:1131	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	2	53	theme	protein	401:407	arg1	deletion					368:375	β-cell-specific deletion	352:375	β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO)	352:445	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	4	54	theme	site-directed	635:647	arg1	mutagenesis					649:659	site-directed mutagenesis	635:659	site-directed mutagenesis	635:659	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	7	55	theme	CPE	1531:1533	arg1	levels					1535:1540	islet CPE levels	1525:1540	islet CPE levels	1525:1540	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	8	56	theme	eIF4G1	1723:1728	arg1	stability					1738:1746	eIF4G1 protein stability	1723:1746	eIF4G1 protein stability	1723:1746	Furthermore, our results reveal that OGT O-GlcNAc-modifies eIF4G1 at Ser-61 and that this modification is critical for eIF4G1 protein stability.
31300553	4	57	theme	EM	730:731	arg1	imaging					733:739	EM imaging	730:739	EM imaging	730:739	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	58	theme	proinsulin	915:924	arg1	processing					926:935	carboxypeptidase E (CPE)-dependent proinsulin processing	880:935	carboxypeptidase E (CPE)-dependent proinsulin processing	880:935	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	7	59	theme	CPE	1487:1489	arg1	translation					1491:1501	CPE translation	1487:1501	CPE translation in β-cells	1487:1512	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	1	60	theme	proinsulin-to-insulin	199:219	arg1	processing					221:230	proinsulin-to-insulin processing	199:230	proinsulin-to-insulin processing	199:230	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	5	61	dep	age	1024:1026	arg1	status					1149:1154	-mediated stress status	1132:1154	-mediated stress status	1132:1154	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	9	62	theme	nutrient-sensitive	1804:1821	arg1	OGT					1823:1825	nutrient-sensitive OGT	1804:1825	nutrient-sensitive OGT	1804:1825	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	6	63	theme	dysfunctional	1294:1306	arg1	ratio					1330:1334	the dysfunctional proinsulin-to-insulin ratio	1290:1334	the dysfunctional proinsulin-to-insulin ratio	1290:1334	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	5	64	theme	βOGTKO	979:984	arg1	hyperproinsulinemia					986:1004	βOGTKO hyperproinsulinemia	979:1004	βOGTKO hyperproinsulinemia	979:1004	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	7	65	theme	eIF4G1	1450:1455	arg1	overexpression					1407:1420	overexpression	1407:1420	overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells,	1407:1513	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	1	66	theme	early	149:153	arg1	failure					188:194	a failure	186:194	a failure	186:194	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	1	66	theme	early	149:153	arg1	hallmark					155:162	An early hallmark	146:162	An early hallmark of type 2 diabetes	146:181	An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia.
31300553	0	67	from	hyperproinsulinemia	117:135	arg1	mice					140:143	mice	140:143	mice	140:143	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	7	68	theme	OGT	1439:1441	arg1	eIF4G1					1450:1455	the suspected OGT target eIF4G1	1425:1455	the suspected OGT target eIF4G1	1425:1455	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	0	69	theme	pancreatic	83:92	arg1	β-cells					94:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	5	70	theme	stress	1142:1147	arg1	status					1149:1154	-mediated stress status	1132:1154	-mediated stress status	1132:1154	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	0	71	from	E	28:28	arg1	β-cells					94:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	6	72	theme	CPE	1261:1263	arg1	reconstitution					1243:1256	genetic reconstitution	1235:1256	genetic reconstitution of CPE in βOGTKO islets	1235:1280	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	4	73	theme	first	757:761	arg1	evidence					763:770	the first evidence	753:770	the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice	753:950	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	9	74	theme	post-translational	1882:1899	arg1	modification					1910:1921	post-translational O-GlcNAc modification	1882:1921	post-translational O-GlcNAc modification	1882:1921	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	4	75	theme	translation	833:843	arg1	eIF4G1					868:873	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	5	76	theme	levels	1042:1047	arg1	independent					1009:1019	independent	1009:1019	independent	1009:1019	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	9	77	theme	modification	1910:1921	arg1	importance					1868:1877	the importance	1864:1877	the importance of post-translational O-GlcNAc modification in general cell physiology	1864:1948	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	4	78	theme	factor	856:861	arg1	eIF4G1					868:873	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	eukaryotic translation initiation factor 4γ1 (eIF4G1)	822:874	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	9	79	theme	general	1926:1932	arg1	physiology					1939:1948	general cell physiology	1926:1948	general cell physiology	1926:1948	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	5	80	theme	protein	1099:1105	arg1	CHOP					1127:1130	CHOP	1127:1130	CHOP	1127:1130	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	5	80	theme	protein	1099:1105	arg1	protein					1118:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein	1054:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)	1054:1131	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	2	81	theme	hyperproinsulinemia	514:532	arg1	development					499:509	early development	493:509	early development of hyperproinsulinemia	493:532	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	4	82	theme	carboxypeptidase	880:895	arg1	E					897:897	carboxypeptidase E	880:897	carboxypeptidase E (CPE)	880:903	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	4	82	theme	carboxypeptidase	880:895	arg1	CPE					900:902	CPE	900:902	CPE	900:902	Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice.
31300553	0	83	theme	O-GlcNAc	52:59	arg1	β-cells					94:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	O-GlcNAc transferase-deficient pancreatic β-cells	52:100	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	5	84	theme	protein	1118:1124	arg1	independent					1009:1019	independent	1009:1019	independent	1009:1019	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	6	85	from	reduction	1197:1205	arg1	CPE					1226:1228	β-cell-resident CPE	1210:1228	β-cell-resident CPE	1210:1228	Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio.
31300553	0	86	dep	eIF4G1	0:5	arg1	dysregulation					35:47	axis dysregulation	30:47	axis dysregulation	30:47	eIF4G1 and carboxypeptidase E axis dysregulation in O-GlcNAc transferase-deficient pancreatic β-cells contributes to hyperproinsulinemia in mice.
31300553	9	87	from	importance	1868:1877	arg1	physiology					1939:1948	general cell physiology	1926:1948	general cell physiology	1926:1948	Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology.
31300553	2	88	theme	β-cell-specific	352:366	arg1	deletion					368:375	β-cell-specific deletion	352:375	β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO)	352:445	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	7	89	theme	islet-induced	1569:1581	arg1	hyperproinsulinemia					1583:1601	βOGTKO islet-induced hyperproinsulinemia	1562:1601	βOGTKO islet-induced hyperproinsulinemia	1562:1601	We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia.
31300553	5	90	theme	reticulum-CCAAT	1066:1080	arg1	CHOP					1127:1130	CHOP	1127:1130	CHOP	1127:1130	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	5	90	theme	reticulum-CCAAT	1066:1080	arg1	protein					1118:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein	1054:1124	endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)	1054:1131	We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status.
31300553	2	91	theme	modifier	409:416	arg1	βOGTKO					439:444	βOGTKO	439:444	βOGTKO	439:444	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
31300553	2	91	theme	modifier	409:416	arg1	transferase					426:436	modifier OGlcNAc transferase	409:436	the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO)	380:445	Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia.
30858176	4	0	theme	purification	554:565	arg1	proteomics					567:576	affinity purification proteomics	545:576	affinity purification proteomics	545:576	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	1	1	from	function	180:187	arg1	system					204:209	the nervous system	192:209	the nervous system	192:209	Inhibitory GABAergic transmission is required for proper circuit function in the nervous system.
30858176	4	2	theme	EEL-1	659:663	arg1	protein					673:679	an EEL-1 binding protein	656:679	an EEL-1 binding protein	656:679	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	4	2	theme	EEL-1	659:663	arg1	OGT-1					647:651	the O-GlcNAc transferase OGT-1	622:651	the O-GlcNAc transferase OGT-1	622:651	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	0	3	theme	ligase	70:75	arg1	EEL-1					77:81	the ubiquitin ligase EEL-1	56:81	the ubiquitin ligase EEL-1	56:81	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	4	4	theme	Caenorhabditis	584:597	arg1	elegans					599:605	Caenorhabditis elegans	584:605	Caenorhabditis elegans	584:605	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	1	5	theme	proper	165:170	arg1	function					180:187	proper circuit function	165:187	proper circuit function in the nervous system	165:209	Inhibitory GABAergic transmission is required for proper circuit function in the nervous system.
30858176	0	6	theme	GABA	93:96	arg1	function					105:112	GABA neuron function	93:112	GABA neuron function	93:112	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	7	7	theme	GABAergic	1003:1011	arg1	neurons					1019:1025	GABAergic motor neurons	1003:1025	GABAergic motor neurons	1003:1025	We observed that, like EEL-1, OGT-1 is expressed in GABAergic motor neurons, localizes to GABAergic presynaptic terminals, and functions cell-autonomously to regulate GABA neuron function.
30858176	8	8	theme	OGT-1	1205:1209	arg1	activity					1231:1238	OGT-1 glycosyltransferase activity	1205:1238	OGT-1 glycosyltransferase activity	1205:1238	Results with catalytically inactive point mutants indicated that OGT-1 glycosyltransferase activity is dispensable for GABA neuron function.
30858176	6	9	theme	cell	937:940	arg1	culture					942:948	cell culture	937:948	cell culture	937:948	Using C. elegans biochemistry, we confirmed that the OGT-1/EEL-1 complex forms in neurons in vivo and showed that the human orthologs, OGT and HUWE1, also bind in cell culture.
30858176	7	10	theme	GABAergic	1041:1049	arg1	terminals					1063:1071	GABAergic presynaptic terminals	1041:1071	GABAergic presynaptic terminals	1041:1071	We observed that, like EEL-1, OGT-1 is expressed in GABAergic motor neurons, localizes to GABAergic presynaptic terminals, and functions cell-autonomously to regulate GABA neuron function.
30858176	4	11	theme	binding	665:671	arg1	protein					673:679	an EEL-1 binding protein	656:679	an EEL-1 binding protein	656:679	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	4	11	theme	binding	665:671	arg1	OGT-1					647:651	the O-GlcNAc transferase OGT-1	622:651	the O-GlcNAc transferase OGT-1	622:651	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	9	12	theme	pharmacology	1376:1387	arg1	assays					1389:1394	automated, behavioral pharmacology assays	1354:1394	automated, behavioral pharmacology assays	1354:1394	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
30858176	10	13	theme	signaling	1539:1547	arg1	complex					1549:1555	a conserved signaling complex	1527:1555	a conserved signaling complex	1527:1555	These findings demonstrate that OGT-1 and EEL-1 form a conserved signaling complex and function together to affect GABA neuron function.
30858176	2	14	theme	GABAergic	293:301	arg1	transmission					303:314	GABAergic transmission	293:314	GABAergic transmission	293:314	However, our understanding of molecular mechanisms that preferentially influence GABAergic transmission, particularly presynaptic mechanisms, remains limited.
30858176	6	15	theme	C.	780:781	arg1	biochemistry					791:802	C. elegans biochemistry	780:802	C. elegans biochemistry	780:802	Using C. elegans biochemistry, we confirmed that the OGT-1/EEL-1 complex forms in neurons in vivo and showed that the human orthologs, OGT and HUWE1, also bind in cell culture.
30858176	1	16	theme	circuit	172:178	arg1	function					180:187	proper circuit function	165:187	proper circuit function in the nervous system	165:209	Inhibitory GABAergic transmission is required for proper circuit function in the nervous system.
30858176	0	17	theme	neuron	98:103	arg1	function					105:112	GABA neuron function	93:112	GABA neuron function	93:112	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	4	18	theme	affinity	545:552	arg1	purification					554:565	affinity purification	545:565	affinity purification proteomics	545:576	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	3	19	theme	presynaptic	461:471	arg1	transmission					473:484	GABAergic presynaptic transmission	451:484	GABAergic presynaptic transmission	451:484	We previously reported that the ubiquitin ligase EEL-1 preferentially regulates GABAergic presynaptic transmission.
30858176	0	20	contain	containing	10:19	arg2	OGT-1					46:50	the O-GlcNAc transferase OGT-1	21:50	the O-GlcNAc transferase OGT-1	21:50	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	0	20	contain	containing	10:19	arg2	EEL-1					77:81	the ubiquitin ligase EEL-1	56:81	the ubiquitin ligase EEL-1	56:81	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	0	20	contain	containing	10:19	arg1	complex					2:8	A complex	0:8	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1	0:81	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	7	21	theme	presynaptic	1051:1061	arg1	terminals					1063:1071	GABAergic presynaptic terminals	1041:1071	GABAergic presynaptic terminals	1041:1071	We observed that, like EEL-1, OGT-1 is expressed in GABAergic motor neurons, localizes to GABAergic presynaptic terminals, and functions cell-autonomously to regulate GABA neuron function.
30858176	9	22	theme	genetic	1332:1338	arg1	results					1340:1346	genetic results	1332:1346	genetic results using automated, behavioral pharmacology assays	1332:1394	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
30858176	7	23	theme	GABA	1118:1121	arg1	function					1130:1137	GABA neuron function	1118:1137	GABA neuron function	1118:1137	We observed that, like EEL-1, OGT-1 is expressed in GABAergic motor neurons, localizes to GABAergic presynaptic terminals, and functions cell-autonomously to regulate GABA neuron function.
30858176	9	24	with	Consistent	1281:1290	arg1	EEL-1					1307:1311	EEL-1	1307:1311	EEL-1	1307:1311	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
30858176	9	24	with	Consistent	1281:1290	arg1	OGT-1					1297:1301	OGT-1	1297:1301	OGT-1	1297:1301	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
30858176	9	25	theme	automated	1354:1362	arg1	assays					1389:1394	automated, behavioral pharmacology assays	1354:1394	automated, behavioral pharmacology assays	1354:1394	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
30858176	4	26	theme	transferase	635:645	arg1	protein					673:679	an EEL-1 binding protein	656:679	an EEL-1 binding protein	656:679	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	4	26	theme	transferase	635:645	arg1	OGT-1					647:651	the O-GlcNAc transferase OGT-1	622:651	the O-GlcNAc transferase OGT-1	622:651	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	7	27	theme	neuron	1123:1128	arg1	function					1130:1137	GABA neuron function	1118:1137	GABA neuron function	1118:1137	We observed that, like EEL-1, OGT-1 is expressed in GABAergic motor neurons, localizes to GABAergic presynaptic terminals, and functions cell-autonomously to regulate GABA neuron function.
30858176	3	28	theme	ubiquitin	403:411	arg1	EEL-1					420:424	the ubiquitin ligase EEL-1	399:424	the ubiquitin ligase EEL-1	399:424	We previously reported that the ubiquitin ligase EEL-1 preferentially regulates GABAergic presynaptic transmission.
30858176	4	29	theme	O-GlcNAc	626:633	arg1	transferase					635:645	the O-GlcNAc transferase	622:645	the O-GlcNAc transferase OGT-1	622:651	To further explore how EEL-1 functions, here we performed affinity purification proteomics using Caenorhabditis elegans and identified the O-GlcNAc transferase OGT-1 as an EEL-1 binding protein.
30858176	6	30	dep	C.	780:781	arg1	elegans					783:789	elegans	783:789	elegans	783:789	Using C. elegans biochemistry, we confirmed that the OGT-1/EEL-1 complex forms in neurons in vivo and showed that the human orthologs, OGT and HUWE1, also bind in cell culture.
30858176	2	31	theme	presynaptic	330:340	arg1	understanding					225:237	our understanding	221:237	our understanding of molecular mechanisms that preferentially influence GABAergic transmission	221:314	However, our understanding of molecular mechanisms that preferentially influence GABAergic transmission, particularly presynaptic mechanisms, remains limited.
30858176	2	31	theme	presynaptic	330:340	arg1	mechanisms					342:351	presynaptic mechanisms	330:351	particularly presynaptic mechanisms	317:351	However, our understanding of molecular mechanisms that preferentially influence GABAergic transmission, particularly presynaptic mechanisms, remains limited.
30858176	1	32	theme	nervous	196:202	arg1	system					204:209	the nervous system	192:209	the nervous system	192:209	Inhibitory GABAergic transmission is required for proper circuit function in the nervous system.
30858176	3	33	theme	ligase	413:418	arg1	EEL-1					420:424	the ubiquitin ligase EEL-1	399:424	the ubiquitin ligase EEL-1	399:424	We previously reported that the ubiquitin ligase EEL-1 preferentially regulates GABAergic presynaptic transmission.
30858176	0	34	theme	transferase	34:44	arg1	OGT-1					46:50	the O-GlcNAc transferase OGT-1	21:50	the O-GlcNAc transferase OGT-1	21:50	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	8	35	theme	GABA	1259:1262	arg1	function					1271:1278	GABA neuron function	1259:1278	GABA neuron function	1259:1278	Results with catalytically inactive point mutants indicated that OGT-1 glycosyltransferase activity is dispensable for GABA neuron function.
30858176	0	36	theme	O-GlcNAc	25:32	arg1	OGT-1					46:50	the O-GlcNAc transferase OGT-1	21:50	the O-GlcNAc transferase OGT-1	21:50	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	8	37	theme	neuron	1264:1269	arg1	function					1271:1278	GABA neuron function	1259:1278	GABA neuron function	1259:1278	Results with catalytically inactive point mutants indicated that OGT-1 glycosyltransferase activity is dispensable for GABA neuron function.
30858176	8	38	theme	glycosyltransferase	1211:1229	arg1	activity					1231:1238	OGT-1 glycosyltransferase activity	1205:1238	OGT-1 glycosyltransferase activity	1205:1238	Results with catalytically inactive point mutants indicated that OGT-1 glycosyltransferase activity is dispensable for GABA neuron function.
30858176	10	39	theme	neuron	1594:1599	arg1	function					1601:1608	GABA neuron function	1589:1608	GABA neuron function	1589:1608	These findings demonstrate that OGT-1 and EEL-1 form a conserved signaling complex and function together to affect GABA neuron function.
30858176	6	40	theme	OGT-1/EEL-1	827:837	arg1	complex					839:845	the OGT-1/EEL-1 complex	823:845	the OGT-1/EEL-1 complex	823:845	Using C. elegans biochemistry, we confirmed that the OGT-1/EEL-1 complex forms in neurons in vivo and showed that the human orthologs, OGT and HUWE1, also bind in cell culture.
30858176	3	41	theme	GABAergic	451:459	arg1	transmission					473:484	GABAergic presynaptic transmission	451:484	GABAergic presynaptic transmission	451:484	We previously reported that the ubiquitin ligase EEL-1 preferentially regulates GABAergic presynaptic transmission.
30858176	10	42	theme	GABA	1589:1592	arg1	function					1601:1608	GABA neuron function	1589:1608	GABA neuron function	1589:1608	These findings demonstrate that OGT-1 and EEL-1 form a conserved signaling complex and function together to affect GABA neuron function.
30858176	10	43	theme	conserved	1529:1537	arg1	complex					1549:1555	a conserved signaling complex	1527:1555	a conserved signaling complex	1527:1555	These findings demonstrate that OGT-1 and EEL-1 form a conserved signaling complex and function together to affect GABA neuron function.
30858176	1	44	theme	Inhibitory	115:124	arg1	transmission					136:147	Inhibitory GABAergic transmission	115:147	Inhibitory GABAergic transmission	115:147	Inhibitory GABAergic transmission is required for proper circuit function in the nervous system.
30858176	5	45	theme	neuron	757:762	arg1	function					764:771	neuron function	757:771	neuron function	757:771	This observation was intriguing, as we know little about how OGT-1 affects neuron function.
30858176	8	46	theme	inactive	1167:1174	arg1	mutants					1182:1188	catalytically inactive point mutants	1153:1188	catalytically inactive point mutants	1153:1188	Results with catalytically inactive point mutants indicated that OGT-1 glycosyltransferase activity is dispensable for GABA neuron function.
30858176	1	47	theme	GABAergic	126:134	arg1	transmission					136:147	Inhibitory GABAergic transmission	115:147	Inhibitory GABAergic transmission	115:147	Inhibitory GABAergic transmission is required for proper circuit function in the nervous system.
30858176	6	48	theme	human	892:896	arg1	orthologs					898:906	the human orthologs	888:906	the human orthologs	888:906	Using C. elegans biochemistry, we confirmed that the OGT-1/EEL-1 complex forms in neurons in vivo and showed that the human orthologs, OGT and HUWE1, also bind in cell culture.
30858176	6	48	theme	human	892:896	arg1	HUWE1					917:921	HUWE1	917:921	HUWE1	917:921	Using C. elegans biochemistry, we confirmed that the OGT-1/EEL-1 complex forms in neurons in vivo and showed that the human orthologs, OGT and HUWE1, also bind in cell culture.
30858176	6	48	theme	human	892:896	arg1	OGT					909:911	OGT	909:911	OGT	909:911	Using C. elegans biochemistry, we confirmed that the OGT-1/EEL-1 complex forms in neurons in vivo and showed that the human orthologs, OGT and HUWE1, also bind in cell culture.
30858176	7	49	theme	motor	1013:1017	arg1	neurons					1019:1025	GABAergic motor neurons	1003:1025	GABAergic motor neurons	1003:1025	We observed that, like EEL-1, OGT-1 is expressed in GABAergic motor neurons, localizes to GABAergic presynaptic terminals, and functions cell-autonomously to regulate GABA neuron function.
30858176	9	50	theme	GABA	1452:1455	arg1	function					1464:1471	GABA neuron function	1452:1471	GABA neuron function	1452:1471	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
30858176	0	51	theme	ubiquitin	60:68	arg1	ligase					70:75	the ubiquitin ligase	56:75	the ubiquitin ligase EEL-1	56:81	A complex containing the O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 regulates GABA neuron function.
30858176	8	52	with	Results	1140:1146	arg1	mutants					1182:1188	catalytically inactive point mutants	1153:1188	catalytically inactive point mutants	1153:1188	Results with catalytically inactive point mutants indicated that OGT-1 glycosyltransferase activity is dispensable for GABA neuron function.
30858176	2	53	theme	mechanisms	252:261	arg1	understanding					225:237	our understanding	221:237	our understanding of molecular mechanisms that preferentially influence GABAergic transmission	221:314	However, our understanding of molecular mechanisms that preferentially influence GABAergic transmission, particularly presynaptic mechanisms, remains limited.
30858176	2	53	theme	mechanisms	252:261	arg1	mechanisms					342:351	presynaptic mechanisms	330:351	particularly presynaptic mechanisms	317:351	However, our understanding of molecular mechanisms that preferentially influence GABAergic transmission, particularly presynaptic mechanisms, remains limited.
30858176	9	54	theme	neuron	1457:1462	arg1	function					1464:1471	GABA neuron function	1452:1471	GABA neuron function	1452:1471	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
30858176	8	55	theme	point	1176:1180	arg1	mutants					1182:1188	catalytically inactive point mutants	1153:1188	catalytically inactive point mutants	1153:1188	Results with catalytically inactive point mutants indicated that OGT-1 glycosyltransferase activity is dispensable for GABA neuron function.
30858176	2	56	theme	molecular	242:250	arg1	mechanisms					252:261	molecular mechanisms	242:261	molecular mechanisms that preferentially influence GABAergic transmission	242:314	However, our understanding of molecular mechanisms that preferentially influence GABAergic transmission, particularly presynaptic mechanisms, remains limited.
30858176	9	57	dep	automated	1354:1362	arg1	behavioral					1365:1374	behavioral	1365:1374	behavioral	1365:1374	Consistent with OGT-1 and EEL-1 forming a complex, genetic results using automated, behavioral pharmacology assays showed that ogt-1 and eel-1 act in parallel to regulate GABA neuron function.
31864627	3	0	from	moieties	596:603	arg1	the					608:610	the	608:610	the	608:610	The sulfonamide derivative was further methylated to generate three permanently charged quaternary ammonium moieties on the label.
31864627	2	1	theme	sulfonamide	412:422	arg1	derivative					424:433	a sulfonamide derivative	410:433	a sulfonamide derivative having three tertiary amines in the label structure	410:485	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	6	2	theme	detection	1018:1026	arg1	limit					1009:1013	the sub-micromolar limit	990:1013	the sub-micromolar limit of detection based on the extracted ion electropherogram signals	990:1078	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	2	3	theme	trisodium	364:372	arg1	salt					374:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	2	3	theme	trisodium	364:372	arg1	compound					317:324	The starting compound	304:324	The starting compound	304:324	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	3	4	theme	charged	568:574	arg1	moieties					596:603	three permanently charged quaternary ammonium moieties	550:603	three permanently charged quaternary ammonium moieties on the label	550:616	The sulfonamide derivative was further methylated to generate three permanently charged quaternary ammonium moieties on the label.
31864627	3	5	theme	quaternary	576:585	arg1	moieties					596:603	three permanently charged quaternary ammonium moieties	550:603	three permanently charged quaternary ammonium moieties on the label	550:616	The sulfonamide derivative was further methylated to generate three permanently charged quaternary ammonium moieties on the label.
31864627	4	6	theme	mass	711:714	arg1	spectrometry					716:727	mass spectrometry	711:727	mass spectrometry	711:727	The synthesized labels were characterized by NMR, IR, UV/Vis, fluorescence spectroscopy and mass spectrometry.
31864627	2	7	theme	acid	359:362	arg1	salt					374:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	2	7	theme	acid	359:362	arg1	compound					317:324	The starting compound	304:324	The starting compound	304:324	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	3	8	theme	sulfonamide	492:502	arg1	derivative					504:513	The sulfonamide derivative	488:513	The sulfonamide derivative	488:513	The sulfonamide derivative was further methylated to generate three permanently charged quaternary ammonium moieties on the label.
31864627	5	9	theme	reductive	843:851	arg1	amination					853:861	reductive amination	843:861	reductive amination	843:861	Furthermore, the labels were applied for maltooligosaccharide standards as well as N-linked glycans labeling via reductive amination and followed by CE-MS analysis.
31864627	2	10	contain	having	435:440	arg1	derivative					424:433	a sulfonamide derivative	410:433	a sulfonamide derivative having three tertiary amines in the label structure	410:485	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	2	10	contain	having	435:440	arg2	amines					457:462	three tertiary amines	442:462	three tertiary amines	442:462	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	5	11	theme	CE-MS	879:883	arg1	analysis					885:892	CE-MS analysis	879:892	CE-MS analysis	879:892	Furthermore, the labels were applied for maltooligosaccharide standards as well as N-linked glycans labeling via reductive amination and followed by CE-MS analysis.
31864627	2	12	theme	8-aminopyrene-1,3,6-trisulfonic	327:357	arg1	salt					374:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	2	12	theme	8-aminopyrene-1,3,6-trisulfonic	327:357	arg1	compound					317:324	The starting compound	304:324	The starting compound	304:324	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	0	13	theme	aminopyrene-based	15:31	arg1	tags					42:45	Multi-cationic aminopyrene-based labeling tags	0:45	Multi-cationic aminopyrene-based labeling tags	0:45	Multi-cationic aminopyrene-based labeling tags for oligosaccharide analysis by capillary electrophoresis-mass spectrometry.
31864627	6	14	theme	sub-micromolar	994:1007	arg1	limit					1009:1013	the sub-micromolar limit	990:1013	the sub-micromolar limit of detection based on the extracted ion electropherogram signals	990:1078	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	1	15	theme	oligosaccharide	223:237	arg1	analysis					239:246	oligosaccharide analysis	223:246	oligosaccharide analysis	223:246	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	0	16	theme	Multi-cationic	0:13	arg1	tags					42:45	Multi-cationic aminopyrene-based labeling tags	0:45	Multi-cationic aminopyrene-based labeling tags	0:45	Multi-cationic aminopyrene-based labeling tags for oligosaccharide analysis by capillary electrophoresis-mass spectrometry.
31864627	6	17	theme	ion	1051:1053	arg1	signals					1072:1078	the extracted ion electropherogram signals	1037:1078	the extracted ion electropherogram signals	1037:1078	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	2	18	theme	tertiary	448:455	arg1	amines					457:462	three tertiary amines	442:462	three tertiary amines	442:462	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	6	19	theme	CE-MS	899:903	arg1	analysis					905:912	The CE-MS analysis	895:912	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels	895:979	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	3	20	dep	the	608:610	arg1	label					612:616	label	612:616	label	612:616	The sulfonamide derivative was further methylated to generate three permanently charged quaternary ammonium moieties on the label.
31864627	6	21	theme	maltooligosaccharides	917:937	arg1	analysis					905:912	The CE-MS analysis	895:912	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels	895:979	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	0	22	theme	labeling	33:40	arg1	tags					42:45	Multi-cationic aminopyrene-based labeling tags	0:45	Multi-cationic aminopyrene-based labeling tags	0:45	Multi-cationic aminopyrene-based labeling tags for oligosaccharide analysis by capillary electrophoresis-mass spectrometry.
31864627	1	23	theme	capillary	251:259	arg1	CE-MS					296:300	CE-MS	296:300	CE-MS	296:300	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	1	23	theme	capillary	251:259	arg1	spectrometry					282:293	capillary electrophoresis-mass spectrometry	251:293	capillary electrophoresis-mass spectrometry (CE-MS)	251:301	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	0	24	theme	oligosaccharide	51:65	arg1	analysis					67:74	oligosaccharide analysis	51:74	oligosaccharide analysis by capillary electrophoresis-mass spectrometry	51:121	Multi-cationic aminopyrene-based labeling tags for oligosaccharide analysis by capillary electrophoresis-mass spectrometry.
31864627	3	25	theme	ammonium	587:594	arg1	moieties					596:603	three permanently charged quaternary ammonium moieties	550:603	three permanently charged quaternary ammonium moieties on the label	550:616	The sulfonamide derivative was further methylated to generate three permanently charged quaternary ammonium moieties on the label.
31864627	1	26	theme	electrophoresis-mass	261:280	arg1	CE-MS					296:300	CE-MS	296:300	CE-MS	296:300	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	1	26	theme	electrophoresis-mass	261:280	arg1	spectrometry					282:293	capillary electrophoresis-mass spectrometry	251:293	capillary electrophoresis-mass spectrometry (CE-MS)	251:301	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	5	27	theme	N-linked	813:820	arg1	glycans					822:828	N-linked glycans	813:828	maltooligosaccharide standards as well as N-linked glycans	771:828	Furthermore, the labels were applied for maltooligosaccharide standards as well as N-linked glycans labeling via reductive amination and followed by CE-MS analysis.
31864627	2	28	theme	label	471:475	arg1	structure					477:485	the label structure	467:485	the label structure	467:485	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	6	29	theme	synthesized	962:972	arg1	labels					974:979	these newly synthesized labels	950:979	these newly synthesized labels	950:979	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	1	30	theme	new	138:140	arg1	tags					184:187	new multi-cationic aminopyrene-based labeling tags	138:187	new multi-cationic aminopyrene-based labeling tags	138:187	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	6	31	theme	electropherogram	1055:1070	arg1	signals					1072:1078	the extracted ion electropherogram signals	1037:1078	the extracted ion electropherogram signals	1037:1078	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	1	32	theme	multi-cationic	142:155	arg1	tags					184:187	new multi-cationic aminopyrene-based labeling tags	138:187	new multi-cationic aminopyrene-based labeling tags	138:187	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	4	33	theme	synthesized	623:633	arg1	labels					635:640	The synthesized labels	619:640	The synthesized labels	619:640	The synthesized labels were characterized by NMR, IR, UV/Vis, fluorescence spectroscopy and mass spectrometry.
31864627	5	34	theme	maltooligosaccharide	771:790	arg1	standards					792:800	maltooligosaccharide standards	771:800	maltooligosaccharide standards as well as N-linked glycans	771:828	Furthermore, the labels were applied for maltooligosaccharide standards as well as N-linked glycans labeling via reductive amination and followed by CE-MS analysis.
31864627	0	35	dep	tags	42:45	arg1	analysis					67:74	oligosaccharide analysis	51:74	oligosaccharide analysis by capillary electrophoresis-mass spectrometry	51:121	Multi-cationic aminopyrene-based labeling tags for oligosaccharide analysis by capillary electrophoresis-mass spectrometry.
31864627	1	36	theme	aminopyrene-based	157:173	arg1	tags					184:187	new multi-cationic aminopyrene-based labeling tags	138:187	new multi-cationic aminopyrene-based labeling tags	138:187	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	4	37	theme	fluorescence	681:692	arg1	spectroscopy					694:705	fluorescence spectroscopy	681:705	fluorescence spectroscopy	681:705	The synthesized labels were characterized by NMR, IR, UV/Vis, fluorescence spectroscopy and mass spectrometry.
31864627	1	38	theme	labeling	175:182	arg1	tags					184:187	new multi-cationic aminopyrene-based labeling tags	138:187	new multi-cationic aminopyrene-based labeling tags	138:187	In this work, new multi-cationic aminopyrene-based labeling tags were designed and synthesized for oligosaccharide analysis by capillary electrophoresis-mass spectrometry (CE-MS).
31864627	0	39	theme	electrophoresis-mass	89:108	arg1	spectrometry					110:121	capillary electrophoresis-mass spectrometry	79:121	capillary electrophoresis-mass spectrometry	79:121	Multi-cationic aminopyrene-based labeling tags for oligosaccharide analysis by capillary electrophoresis-mass spectrometry.
31864627	2	40	theme	starting	308:315	arg1	salt					374:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	8-aminopyrene-1,3,6-trisulfonic acid trisodium salt	327:377	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	2	40	theme	starting	308:315	arg1	compound					317:324	The starting compound	304:324	The starting compound	304:324	The starting compound, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt, was modified in order to form a sulfonamide derivative having three tertiary amines in the label structure.
31864627	0	41	theme	capillary	79:87	arg1	spectrometry					110:121	capillary electrophoresis-mass spectrometry	79:121	capillary electrophoresis-mass spectrometry	79:121	Multi-cationic aminopyrene-based labeling tags for oligosaccharide analysis by capillary electrophoresis-mass spectrometry.
31864627	6	42	theme	extracted	1041:1049	arg1	signals					1072:1078	the extracted ion electropherogram signals	1037:1078	the extracted ion electropherogram signals	1037:1078	The CE-MS analysis of maltooligosaccharides labeled by these newly synthesized labels provided the sub-micromolar limit of detection based on the extracted ion electropherogram signals.
31864627	5	43	link	N-linked	813:820	arg1	glycans					822:828	N-linked glycans	813:828	maltooligosaccharide standards as well as N-linked glycans	771:828	Furthermore, the labels were applied for maltooligosaccharide standards as well as N-linked glycans labeling via reductive amination and followed by CE-MS analysis.
30709903	7	0	theme	O-GlcNAc	1276:1283	arg1	levels					1285:1290	increased O-GlcNAc levels	1266:1290	increased O-GlcNAc levels in adipose tissue	1266:1308	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	9	1	theme	protein	1709:1715	arg1	levels					1717:1722	OGT mRNA and protein levels	1696:1722	OGT mRNA and protein levels	1696:1722	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	5	2	theme	O-glycosyltransferase	890:910	arg1	inhibition					876:885	inhibition	876:885	inhibition of O-glycosyltransferase (OGT)	876:916	Glucosamine treatment, which bypasses the rate-limiting step in the synthesis of substrate for glycosylation, increased both O-GlcNAc and leptin, whereas inhibition of O-glycosyltransferase (OGT) decreased O-GlcNAc and leptin.
30709903	6	3	theme	leptin	963:968	arg1	susceptible					1005:1015	susceptible	1005:1015	susceptible	1005:1015	The increased leptin levels induced by glucosamine were susceptible to the inhibition by iron, but in the case of OGT inhibition, iron did not further decrease leptin.
30709903	6	3	theme	leptin	963:968	arg1	levels					970:975	The increased leptin levels	949:975	The increased leptin levels induced by glucosamine	949:998	The increased leptin levels induced by glucosamine were susceptible to the inhibition by iron, but in the case of OGT inhibition, iron did not further decrease leptin.
30709903	1	4	theme	response	269:276	arg1	pCREB					303:307	pCREB	303:307	pCREB	303:307	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	1	4	theme	response	269:276	arg1	protein					294:300	phosphorylated cAMP response element-binding protein	249:300	phosphorylated cAMP response element-binding protein (pCREB)	249:308	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	5	5	theme	rate-limiting	764:776	arg1	step					778:781	the rate-limiting step	760:781	the rate-limiting step in the synthesis of substrate for glycosylation	760:829	Glucosamine treatment, which bypasses the rate-limiting step in the synthesis of substrate for glycosylation, increased both O-GlcNAc and leptin, whereas inhibition of O-glycosyltransferase (OGT) decreased O-GlcNAc and leptin.
30709903	4	6	theme	high	560:563	arg1	iron					565:568	high iron	560:568	high iron	560:568	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	2	7	theme	nutrient-sensing	360:375	arg1	pathways					377:384	Several nutrient-sensing pathways	352:384	Several nutrient-sensing pathways including O-GlcNAcylation	352:410	Several nutrient-sensing pathways including O-GlcNAcylation also regulate leptin.
30709903	2	7	theme	nutrient-sensing	360:375	arg1	O-GlcNAcylation					396:410	O-GlcNAcylation	396:410	O-GlcNAcylation	396:410	Several nutrient-sensing pathways including O-GlcNAcylation also regulate leptin.
30709903	1	8	theme	element-binding	278:292	arg1	pCREB					303:307	pCREB	303:307	pCREB	303:307	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	1	8	theme	element-binding	278:292	arg1	protein					294:300	phosphorylated cAMP response element-binding protein	249:300	phosphorylated cAMP response element-binding protein (pCREB)	249:308	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	0	9	theme	decreased	100:108	arg1	levels					110:115	decreased levels	100:115	decreased levels of O-glycosylated CREB	100:138	Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.
30709903	1	10	from	sites	317:321	arg1	promoter					342:349	the leptin gene promoter	326:349	the leptin gene promoter	326:349	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	1	11	gly	occupancy	236:244	arg2	pCREB					303:307	pCREB	303:307	pCREB	303:307	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	1	11	gly	occupancy	236:244	arg2	protein					294:300	phosphorylated cAMP response element-binding protein	249:300	phosphorylated cAMP response element-binding protein (pCREB)	249:308	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	1	12	theme	protein	294:300	arg1	occupancy					236:244	occupancy	236:244	occupancy of phosphorylated cAMP response element-binding protein (pCREB)	236:308	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	7	13	theme	increased	1266:1274	arg1	levels					1285:1290	increased O-GlcNAc levels	1266:1290	increased O-GlcNAc levels in adipose tissue	1266:1308	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	0	14	from	modification	59:70	arg1	adipocytes					75:84	adipocytes	75:84	adipocytes	75:84	Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.
30709903	5	15	theme	Glucosamine	722:732	arg1	treatment					734:742	Glucosamine treatment	722:742	Glucosamine treatment	722:742	Glucosamine treatment, which bypasses the rate-limiting step in the synthesis of substrate for glycosylation, increased both O-GlcNAc and leptin, whereas inhibition of O-glycosyltransferase (OGT) decreased O-GlcNAc and leptin.
30709903	7	16	theme	heterozygous	1183:1194	arg1	deletion					1196:1203	whole-body heterozygous deletion	1172:1203	whole-body heterozygous deletion	1172:1203	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	7	17	theme	gene	1155:1158	arg1	deletion					1127:1134	deletion	1127:1134	deletion of the O-GlcNAcase gene	1127:1158	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	0	18	gly	O-glycosylated	120:133	arg1	CREB					135:138	O-glycosylated CREB	120:138	O-glycosylated CREB	120:138	Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.
30709903	3	19	theme	CREB-mediated	510:522	arg1	regulation					524:533	iron- and CREB-mediated regulation	500:533	iron- and CREB-mediated regulation of leptin	500:543	We therefore investigated whether O-glycosylation plays a role in iron- and CREB-mediated regulation of leptin.
30709903	8	20	theme	pCREB	1408:1412	arg1	occupancy					1395:1403	the occupancy	1391:1403	the occupancy of pCREB	1391:1412	Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter.
30709903	5	21	theme	substrate	803:811	arg1	synthesis					790:798	the synthesis	786:798	the synthesis of substrate	786:811	Glucosamine treatment, which bypasses the rate-limiting step in the synthesis of substrate for glycosylation, increased both O-GlcNAc and leptin, whereas inhibition of O-glycosyltransferase (OGT) decreased O-GlcNAc and leptin.
30709903	4	22	from	O-GlcNAcylation	588:602	arg1	adipocytes					628:637	cultured 3T3-L1 adipocytes	612:637	cultured 3T3-L1 adipocytes	612:637	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	4	22	from	O-GlcNAcylation	588:602	arg1	mice					646:649	mice	646:649	mice fed high-iron diets	646:669	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	7	23	from	levels	1331:1336	arg1	tissue					1303:1308	adipose tissue	1295:1308	adipose tissue	1295:1308	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	4	24	theme	protein	580:586	arg1	O-GlcNAcylation					588:602	protein O-GlcNAcylation	580:602	protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets	580:669	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	4	25	theme	protein	706:712	arg1	levels					714:719	leptin mRNA and protein levels	690:719	levels	714:719	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	7	26	theme	adipocyte-targeted	1216:1233	arg1	deletion					1246:1253	adipocyte-targeted homozygous deletion	1216:1253	adipocyte-targeted homozygous deletion	1216:1253	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	10	27	theme	CREB	1804:1807	arg1	glycosylation					1809:1821	CREB glycosylation	1804:1821	CREB glycosylation	1804:1821	We conclude that iron down-regulates leptin by decreasing CREB glycosylation, resulting in increased CREB phosphorylation and leptin promoter occupancy by pCREB.
30709903	5	28	dep	increased	832:840	arg1	whereas					868:874	whereas	868:874	whereas	868:874	Glucosamine treatment, which bypasses the rate-limiting step in the synthesis of substrate for glycosylation, increased both O-GlcNAc and leptin, whereas inhibition of O-glycosyltransferase (OGT) decreased O-GlcNAc and leptin.
30709903	6	29	theme	increased	953:961	arg1	susceptible					1005:1015	susceptible	1005:1015	susceptible	1005:1015	The increased leptin levels induced by glucosamine were susceptible to the inhibition by iron, but in the case of OGT inhibition, iron did not further decrease leptin.
30709903	6	29	theme	increased	953:961	arg1	levels					970:975	The increased leptin levels	949:975	The increased leptin levels induced by glucosamine	949:998	The increased leptin levels induced by glucosamine were susceptible to the inhibition by iron, but in the case of OGT inhibition, iron did not further decrease leptin.
30709903	9	30	theme	experimental	1520:1531	arg1	models					1533:1538	our experimental models	1516:1538	our experimental models	1516:1538	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	7	31	theme	homozygous	1235:1244	arg1	deletion					1246:1253	adipocyte-targeted homozygous deletion	1216:1253	adipocyte-targeted homozygous deletion	1216:1253	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	9	32	theme	increasing	1628:1637	arg1	deglycosylation					1647:1661	increasing protein deglycosylation	1628:1661	increasing protein deglycosylation	1628:1661	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	10	33	theme	promoter	1879:1886	arg1	occupancy					1888:1896	leptin promoter occupancy	1872:1896	leptin promoter occupancy	1872:1896	We conclude that iron down-regulates leptin by decreasing CREB glycosylation, resulting in increased CREB phosphorylation and leptin promoter occupancy by pCREB.
30709903	8	34	gly	occupancy	1395:1403	arg2	pCREB					1408:1412	pCREB	1408:1412	pCREB	1408:1412	Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter.
30709903	0	35	theme	CREB	135:138	arg1	levels					110:115	decreased levels	100:115	decreased levels of O-glycosylated CREB	100:138	Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.
30709903	10	36	theme	leptin	1872:1877	arg1	occupancy					1888:1896	leptin promoter occupancy	1872:1896	leptin promoter occupancy	1872:1896	We conclude that iron down-regulates leptin by decreasing CREB glycosylation, resulting in increased CREB phosphorylation and leptin promoter occupancy by pCREB.
30709903	9	37	theme	protein	1639:1645	arg1	deglycosylation					1647:1661	increasing protein deglycosylation	1628:1661	increasing protein deglycosylation	1628:1661	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	8	38	theme	O-GlcNAcylated	1445:1458	arg1	CREB					1460:1463	O-GlcNAcylated CREB	1445:1463	O-GlcNAcylated CREB	1445:1463	Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter.
30709903	1	39	theme	leptin	210:215	arg1	gene					217:220	the leptin gene	206:220	the leptin gene	206:220	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	4	40	theme	3T3-L1	621:626	arg1	adipocytes					628:637	cultured 3T3-L1 adipocytes	612:637	cultured 3T3-L1 adipocytes	612:637	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	0	41	theme	O-glycosylated	120:133	arg1	CREB					135:138	O-glycosylated CREB	120:138	O-glycosylated CREB	120:138	Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.
30709903	10	42	theme	increased	1837:1845	arg1	phosphorylation					1852:1866	increased CREB phosphorylation	1837:1866	increased CREB phosphorylation	1837:1866	We conclude that iron down-regulates leptin by decreasing CREB glycosylation, resulting in increased CREB phosphorylation and leptin promoter occupancy by pCREB.
30709903	1	43	theme	gene	217:220	arg1	transcription					189:201	transcription	189:201	transcription of the leptin gene	189:220	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	0	44	theme	protein	42:48	arg1	modification					59:70	protein O-GlcNAc modification	42:70	protein O-GlcNAc modification	42:70	Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.
30709903	4	45	theme	cultured	612:619	arg1	adipocytes					628:637	cultured 3T3-L1 adipocytes	612:637	cultured 3T3-L1 adipocytes	612:637	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	8	46	gly	occupancy	1432:1440	arg2	CREB					1460:1463	O-GlcNAcylated CREB	1445:1463	O-GlcNAcylated CREB	1445:1463	Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter.
30709903	6	47	theme	OGT	1063:1065	arg1	inhibition					1067:1076	OGT inhibition	1063:1076	OGT inhibition	1063:1076	The increased leptin levels induced by glucosamine were susceptible to the inhibition by iron, but in the case of OGT inhibition, iron did not further decrease leptin.
30709903	5	48	from	step	778:781	arg1	synthesis					790:798	the synthesis	786:798	the synthesis of substrate	786:811	Glucosamine treatment, which bypasses the rate-limiting step in the synthesis of substrate for glycosylation, increased both O-GlcNAc and leptin, whereas inhibition of O-glycosyltransferase (OGT) decreased O-GlcNAc and leptin.
30709903	3	49	theme	iron-	500:504	arg1	regulation					524:533	iron- and CREB-mediated regulation	500:533	iron- and CREB-mediated regulation of leptin	500:543	We therefore investigated whether O-glycosylation plays a role in iron- and CREB-mediated regulation of leptin.
30709903	2	50	theme	Several	352:358	arg1	pathways					377:384	Several nutrient-sensing pathways	352:384	Several nutrient-sensing pathways including O-GlcNAcylation	352:410	Several nutrient-sensing pathways including O-GlcNAcylation also regulate leptin.
30709903	2	50	theme	Several	352:358	arg1	O-GlcNAcylation					396:410	O-GlcNAcylation	396:410	O-GlcNAcylation	396:410	Several nutrient-sensing pathways including O-GlcNAcylation also regulate leptin.
30709903	3	51	theme	leptin	538:543	arg1	regulation					524:533	iron- and CREB-mediated regulation	500:533	iron- and CREB-mediated regulation of leptin	500:543	We therefore investigated whether O-glycosylation plays a role in iron- and CREB-mediated regulation of leptin.
30709903	0	52	theme	O-GlcNAc	50:57	arg1	modification					59:70	protein O-GlcNAc modification	42:70	protein O-GlcNAc modification	42:70	Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.
30709903	8	53	theme	CREB	1460:1463	arg1	occupancy					1432:1440	the occupancy	1428:1440	the occupancy of O-GlcNAcylated CREB on the leptin promoter	1428:1486	Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter.
30709903	7	54	theme	O-GlcNAcase	1143:1153	arg1	gene					1155:1158	the O-GlcNAcase gene	1139:1158	the O-GlcNAcase gene	1139:1158	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	8	55	theme	leptin	1472:1477	arg1	promoter					1479:1486	the leptin promoter	1468:1486	the leptin promoter	1468:1486	Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter.
30709903	1	56	theme	leptin	330:335	arg1	promoter					342:349	the leptin gene promoter	326:349	the leptin gene promoter	326:349	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	7	57	from	levels	1285:1290	arg1	tissue					1303:1308	adipose tissue	1295:1308	adipose tissue	1295:1308	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	7	58	theme	whole-body	1172:1181	arg1	deletion					1196:1203	whole-body heterozygous deletion	1172:1203	whole-body heterozygous deletion	1172:1203	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	10	59	theme	CREB	1847:1850	arg1	phosphorylation					1852:1866	increased CREB phosphorylation	1837:1866	increased CREB phosphorylation	1837:1866	We conclude that iron down-regulates leptin by decreasing CREB glycosylation, resulting in increased CREB phosphorylation and leptin promoter occupancy by pCREB.
30709903	4	60	theme	high-iron	655:663	arg1	diets					665:669	high-iron diets	655:669	high-iron diets	655:669	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	9	61	theme	OGT	1696:1698	arg1	mRNA					1700:1703	OGT mRNA	1696:1703	OGT mRNA	1696:1703	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	9	62	located	observed	1504:1511	arg1	models					1533:1538	our experimental models	1516:1538	our experimental models	1516:1538	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	9	62	located	observed	1504:1511	arg2	patterns					1495:1502	These patterns	1489:1502	These patterns observed in our experimental models	1489:1538	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	6	63	theme	inhibition	1067:1076	arg1	case					1055:1058	the case	1051:1058	the case of OGT inhibition	1051:1076	The increased leptin levels induced by glucosamine were susceptible to the inhibition by iron, but in the case of OGT inhibition, iron did not further decrease leptin.
30709903	7	64	with	Mice	1117:1120	arg1	deletion					1127:1134	deletion	1127:1134	deletion of the O-GlcNAcase gene	1127:1158	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	9	65	theme	mRNA	1700:1703	arg1	levels					1717:1722	OGT mRNA and protein levels	1696:1722	OGT mRNA and protein levels	1696:1722	These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron.
30709903	4	66	theme	leptin	690:695	arg1	mRNA					697:700	leptin mRNA and protein levels	690:719	mRNA	697:700	We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels.
30709903	7	67	theme	increased	1314:1322	arg1	levels					1331:1336	increased leptin levels	1314:1336	increased leptin levels that were inhibited by iron	1314:1364	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	1	68	theme	phosphorylated	249:262	arg1	pCREB					303:307	pCREB	303:307	pCREB	303:307	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	1	68	theme	phosphorylated	249:262	arg1	protein					294:300	phosphorylated cAMP response element-binding protein	249:300	phosphorylated cAMP response element-binding protein (pCREB)	249:308	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	7	69	theme	adipose	1295:1301	arg1	tissue					1303:1308	adipose tissue	1295:1308	adipose tissue	1295:1308	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	1	70	theme	gene	337:340	arg1	promoter					342:349	the leptin gene promoter	326:349	the leptin gene promoter	326:349	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	7	71	theme	leptin	1324:1329	arg1	levels					1331:1336	increased leptin levels	1314:1336	increased leptin levels that were inhibited by iron	1314:1364	Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron.
30709903	8	72	from	occupancy	1432:1440	arg1	promoter					1479:1486	the leptin promoter	1468:1486	the leptin promoter	1468:1486	Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter.
30709903	1	73	theme	cAMP	264:267	arg1	pCREB					303:307	pCREB	303:307	pCREB	303:307	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30709903	1	73	theme	cAMP	264:267	arg1	protein					294:300	phosphorylated cAMP response element-binding protein	249:300	phosphorylated cAMP response element-binding protein (pCREB)	249:308	We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter.
30996101	7	0	theme	men	1425:1427	arg1	two					1412:1414	two	1412:1414	two	1412:1414	Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men.
30996101	7	0	theme	men	1425:1427	arg1	men					1425:1427	eight men	1419:1427	eight men	1419:1427	Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men.
30996101	13	1	theme	blood	2413:2417	arg1	variants					2437:2444	both the blood and genital tract variants	2404:2444	variants	2437:2444	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	12	2	theme	blood	2323:2327	arg1	variants					2329:2336	the blood variants	2319:2336	the blood variants	2319:2336	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	1	3	theme	genetic	233:239	arg1	characteristics					241:255	the genetic characteristics	229:255	the genetic characteristics of blood and genital viruses from males	229:295	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	6	4	theme	transmitting	1185:1196	arg1	partner					1203:1209	their transmitting male partner	1179:1209	their transmitting male partner	1179:1209	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	1	5	from	males	291:295	arg1	blood					260:264	blood	260:264	blood	260:264	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	5	from	males	291:295	arg1	viruses					278:284	genital viruses	270:284	genital viruses	270:284	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	5	from	males	291:295	arg1	characteristics					241:255	the genetic characteristics	229:255	the genetic characteristics of blood and genital viruses from males	229:295	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	8	6	theme	fewer	1594:1598	arg1	sites					1623:1627	fewer N-linked glycosylation sites	1594:1627	fewer N-linked glycosylation sites	1594:1627	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	11	7	theme	characteristics	2080:2094	arg1	Identification					2052:2065	Identification	2052:2065	Identification of the viral characteristics associated with transmission	2052:2123	Identification of the viral characteristics associated with transmission would facilitate vaccine design.
30996101	12	8	from	variants	2329:2336	arg1	distinct					2305:2312	distinct	2305:2312	distinct	2305:2312	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	8	9	theme	glycosylation	1609:1621	arg1	sites					1623:1627	fewer N-linked glycosylation sites	1594:1627	fewer N-linked glycosylation sites	1594:1627	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	5	10	theme	viral	864:868	arg1	populations					870:880	the women's founding viral populations	843:880	the women's founding viral populations	843:880	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	7	11	theme	genital	1340:1346	arg1	viruses					1348:1354	the blood and genital viruses	1326:1354	the blood and genital viruses	1326:1354	Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men.
30996101	10	12	theme	infections	2040:2049	arg1	majority					2022:2029	the majority	2018:2029	the majority of HIV-1 infections	2018:2049	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	10	13	theme	blood	1885:1889	arg1	virus					1891:1895	cell-free blood virus	1875:1895	cell-free blood virus	1875:1895	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	1	14	theme	human	184:188	arg1	type					213:216	human immunodeficiency virus type 1	184:218	human immunodeficiency virus type 1 (HIV-1)	184:226	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	14	theme	human	184:188	arg1	HIV-1					221:225	HIV-1	221:225	HIV-1	221:225	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	5	15	dep	these	779:783	arg1	couples					785:791	couples	785:791	couples' sequences	785:802	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	7	16	theme	blood	1330:1334	arg1	viruses					1348:1354	the blood and genital viruses	1326:1354	the blood and genital viruses	1326:1354	Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men.
30996101	6	17	theme	clades	1282:1287	arg1	number					1266:1271	a greater number	1256:1271	a greater number of viral clades	1256:1287	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	3	18	theme	Single	585:590	arg1	templates					598:606	Single viral templates	585:606	Single viral templates from blood plasma and genital tract RNA and DNA	585:654	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	3	19	dep	tract	638:642	arg1	DNA					652:654	DNA	652:654	DNA	652:654	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	3	19	dep	tract	638:642	arg1	RNA					644:646	RNA	644:646	RNA	644:646	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	2	20	theme	transmission	558:569	arg1	time					550:553	the time	546:553	the time of transmission	546:569	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	0	21	from	Blood	72:76	arg1	Comparisons					0:10	Comparisons	0:10	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.	0:141	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	6	22	theme	partner	1203:1209	arg1	viruses					1168:1174	the blood viruses	1158:1174	the blood viruses of their transmitting male partner	1158:1209	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	10	23	theme	HIV-1	1913:1917	arg1	sequences					1919:1927	HIV-1 sequences	1913:1927	HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections	1913:2049	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	0	24	theme	Male-to-Female	114:127	arg1	Transmission					129:140	Male-to-Female Transmission	114:140	Male-to-Female Transmission	114:140	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	1	25	theme	female	370:375	arg1	partners					377:384	their female partners	364:384	their female partners	364:384	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	0	26	from	Variants	60:67	arg1	Blood					72:76	Blood	72:76	Blood	72:76	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	0	26	from	Variants	60:67	arg1	Fluids					90:95	Genital Fluids	82:95	Genital Fluids	82:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	7	27	theme	multiple	1309:1316	arg1	assays					1318:1323	multiple assays	1309:1323	multiple assays	1309:1323	Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men.
30996101	6	28	theme	greater	1258:1264	arg1	number					1266:1271	a greater number	1256:1271	a greater number of viral clades	1256:1287	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	3	29	theme	blood	613:617	arg1	plasma					619:624	blood plasma	613:624	blood plasma	613:624	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	14	30	theme	targeting	2565:2573	arg1	responses					2583:2591	targeting vaccine responses	2565:2591	targeting vaccine responses to variants found in blood	2565:2618	These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.
30996101	10	31	theme	those	1947:1951	arg1	representative					1929:1942	representative	1929:1942	representative	1929:1942	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	13	32	theme	tract	2431:2435	arg1	variants					2437:2444	both the blood and genital tract variants	2404:2444	variants	2437:2444	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	5	33	theme	CCR5	925:928	arg1	tropic					930:935	CCR5 tropic	925:935	CCR5 tropic	925:935	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	6	34	theme	genetic	1009:1015	arg1	distance					1017:1024	The median genetic distance	998:1024	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses	998:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	6	35	theme	blood	1162:1166	arg1	viruses					1168:1174	the blood viruses	1158:1174	the blood viruses of their transmitting male partner	1158:1209	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	10	36	theme	representative	1929:1942	arg1	sequences					1919:1927	HIV-1 sequences	1913:1927	HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections	1913:2049	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	0	37	theme	Variants	60:67	arg1	Comparisons					0:10	Comparisons	0:10	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.	0:141	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	8	38	attach	link	1499:1502	arg2	signatures					1453:1462	No distinct amino acid signatures	1430:1462	No distinct amino acid signatures in the men's viruses	1430:1483	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	8	38	attach	link	1499:1502	arg1	founders					1519:1526	the women's founders	1507:1526	the women's founders	1507:1526	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	9	39	theme	factors	1652:1658	arg1	consistent					1695:1704	consistent	1695:1704	consistent	1695:1704	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	9	39	theme	factors	1652:1658	arg1	lack					1634:1637	The lack	1630:1637	The lack of selective factors	1630:1658	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	1	40	theme	genital	270:276	arg1	viruses					278:284	genital viruses	270:284	genital viruses	270:284	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	10	41	theme	semen.IMPORTANCE	1967:1982	arg1	transmissions					1992:2004	semen.IMPORTANCE Mucosal transmissions	1967:2004	semen.IMPORTANCE Mucosal transmissions	1967:2004	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	5	42	theme	viral	902:906	arg1	variant					908:914	a single viral variant	893:914	a single viral variant	893:914	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	0	43	from	Comparisons	0:10	arg1	Blood					72:76	Blood	72:76	Blood	72:76	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	0	43	from	Comparisons	0:10	arg1	Fluids					90:95	Genital Fluids	82:95	Genital Fluids	82:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	12	44	theme	transmitting	2189:2200	arg1	males					2202:2206	transmitting males	2189:2206	transmitting males	2189:2206	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	0	45	theme	Genital	82:88	arg1	Fluids					90:95	Genital Fluids	82:95	Genital Fluids	82:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	1	46	theme	imputed	327:333	arg1	population					350:359	the imputed founding virus population	323:359	the imputed founding virus population in their female partners	323:384	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	4	47	dep	29	704:705	arg1	couples					707:713	couples	707:713	couples	707:713	Eight of 29 couples examined yielded viral sequences from both tissues.
30996101	9	48	theme	coreceptor	1672:1681	arg1	tropism					1683:1689	coreceptor tropism	1672:1689	coreceptor tropism	1672:1689	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	8	49	theme	acid	1448:1451	arg1	signatures					1453:1462	No distinct amino acid signatures	1430:1462	No distinct amino acid signatures in the men's viruses	1430:1483	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	3	50	from	tract	638:642	arg1	templates					598:606	Single viral templates	585:606	Single viral templates from blood plasma and genital tract RNA and DNA	585:654	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	1	51	theme	virus	344:348	arg1	population					350:359	the imputed founding virus population	323:359	the imputed founding virus population in their female partners	323:384	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	2	52	dep	African	425:431	arg1	couples					433:439	couples	433:439	couples with sequence-confirmed male-to-female HIV-1 transmission and blood	433:507	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	6	53	theme	ancestor	1060:1067	arg1	distance					1017:1024	The median genetic distance	998:1024	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses	998:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	2	54	theme	sequence-confirmed	446:463	arg1	transmission					486:497	sequence-confirmed male-to-female HIV-1 transmission	446:497	sequence-confirmed male-to-female HIV-1 transmission	446:497	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	12	55	theme	female	2233:2238	arg1	partners					2240:2247	their seroconverting female partners	2212:2247	their seroconverting female partners	2212:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	1	56	from	population	350:359	arg1	partners					377:384	their female partners	364:384	their female partners	364:384	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	57	theme	blood	260:264	arg1	characteristics					241:255	the genetic characteristics	229:255	the genetic characteristics of blood and genital viruses from males	229:295	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	11	58	theme	vaccine	2142:2148	arg1	design					2150:2155	vaccine design	2142:2155	vaccine design	2142:2155	Identification of the viral characteristics associated with transmission would facilitate vaccine design.
30996101	6	59	theme	recent	1046:1051	arg1	ancestor					1060:1067	the imputed most recent common ancestor	1029:1067	the imputed most recent common ancestor of the women's founder viruses	1029:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	12	60	theme	strains	2176:2182	arg1	study					2163:2167	This study	2158:2167	This study of HIV strains from transmitting males and their seroconverting female partners	2158:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	13	61	from	viruses	2359:2365	arg1	women					2370:2374	women	2370:2374	women	2370:2374	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	2	62	theme	heterosexual	412:423	arg1	specimens					521:529	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens	387:529	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission	387:569	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	0	63	theme	Human	15:19	arg1	Type					44:47	Human Immunodeficiency Virus Type 1	15:49	Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids	15:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	5	64	located	detected	970:977	arg1	males					991:995	four males	986:995	four males	986:995	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	5	64	located	detected	970:977	arg2	variants					956:963	CXCR4 variants	950:963	CXCR4 variants	950:963	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	8	65	link	N-linked	1600:1607	arg1	sites					1623:1627	fewer N-linked glycosylation sites	1594:1627	fewer N-linked glycosylation sites	1594:1627	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	6	66	theme	imputed	1033:1039	arg1	ancestor					1060:1067	the imputed most recent common ancestor	1029:1067	the imputed most recent common ancestor of the women's founder viruses	1029:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	0	67	theme	Virus	38:42	arg1	Type					44:47	Human Immunodeficiency Virus Type 1	15:49	Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids	15:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	12	68	dep	males	2264:2268	arg1	tract					2279:2283	genital tract	2271:2283	the males' genital tract viruses	2260:2291	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	13	69	theme	tract-specific	2512:2525	arg1	lineages					2527:2534	genital tract-specific lineages	2504:2534	genital tract-specific lineages	2504:2534	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	13	70	theme	imputed	2343:2349	arg1	similar					2393:2399	similar	2393:2399	similar	2393:2399	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	13	70	theme	imputed	2343:2349	arg1	viruses					2359:2365	The imputed founder viruses	2339:2365	The imputed founder viruses in women	2339:2374	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	2	71	theme	HIV-1	480:484	arg1	transmission					486:497	sequence-confirmed male-to-female HIV-1 transmission	446:497	sequence-confirmed male-to-female HIV-1 transmission	446:497	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	9	72	theme	selective	1642:1650	arg1	factors					1652:1658	selective factors	1642:1658	selective factors	1642:1658	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	13	73	theme	male	2455:2458	arg1	partners					2460:2467	their male partners	2449:2467	their male partners	2449:2467	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	14	74	theme	genital	2652:2658	arg1	variants					2666:2673	genital tract variants	2652:2673	genital tract variants	2652:2673	These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.
30996101	9	75	theme	male-to-female	1731:1744	arg1	transmissions					1760:1772	male-to-female and high-risk transmissions	1731:1772	male-to-female and high-risk transmissions	1731:1772	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	10	76	theme	infrequent	1779:1788	arg1	compartmentalization					1790:1809	The infrequent compartmentalization	1775:1809	The infrequent compartmentalization between the transmitters' blood and semen viruses	1775:1859	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	6	77	theme	viruses	1092:1098	arg1	ancestor					1060:1067	the imputed most recent common ancestor	1029:1067	the imputed most recent common ancestor of the women's founder viruses	1029:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	9	78	theme	high-risk	1750:1758	arg1	transmissions					1760:1772	male-to-female and high-risk transmissions	1731:1772	male-to-female and high-risk transmissions	1731:1772	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	3	79	theme	env	684:686	arg1	gp160					688:692	HIV-1 env gp160	678:692	HIV-1 env gp160	678:692	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	8	80	theme	env	1549:1551	arg1	sequences					1553:1561	the women's env sequences	1537:1561	the women's env sequences	1537:1561	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	6	81	from	detection	1243:1251	arg1	blood					1296:1300	the blood	1292:1300	the blood	1292:1300	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	8	82	from	signatures	1453:1462	arg1	viruses					1477:1483	the men's viruses	1467:1483	the men's viruses	1467:1483	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	9	83	from	findings	1719:1726	arg1	transmissions					1760:1772	male-to-female and high-risk transmissions	1731:1772	male-to-female and high-risk transmissions	1731:1772	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	10	84	theme	HIV-1	2034:2038	arg1	infections					2040:2049	HIV-1 infections	2034:2049	HIV-1 infections	2034:2049	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	13	85	theme	evidence	2491:2498	arg1	lack					2483:2486	a lack	2481:2486	a lack of evidence for genital tract-specific lineages	2481:2534	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	8	86	theme	variable	1576:1583	arg1	loops					1585:1589	shorter variable loops	1568:1589	shorter variable loops	1568:1589	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	9	87	with	consistent	1695:1704	arg1	findings					1719:1726	others' findings	1711:1726	others' findings in male-to-female and high-risk transmissions	1711:1772	The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions.
30996101	13	88	theme	genital	2504:2510	arg1	lineages					2527:2534	genital tract-specific lineages	2504:2534	genital tract-specific lineages	2504:2534	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	10	89	theme	semen	1847:1851	arg1	viruses					1853:1859	semen viruses	1847:1859	semen viruses	1847:1859	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	13	90	theme	partners	2460:2467	arg1	variants					2437:2444	both the blood and genital tract variants	2404:2444	variants	2437:2444	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	12	91	from	males	2202:2206	arg1	study					2163:2167	This study	2158:2167	This study of HIV strains from transmitting males and their seroconverting female partners	2158:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	12	91	from	males	2202:2206	arg1	strains					2176:2182	HIV strains	2172:2182	HIV strains from transmitting males and their seroconverting female partners	2172:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	5	92	theme	founding	855:862	arg1	populations					870:880	the women's founding viral populations	843:880	the women's founding viral populations	843:880	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	6	93	theme	semen	1136:1140	arg1	viruses					1142:1148	the semen viruses	1132:1148	the semen viruses	1132:1148	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	3	94	theme	viral	592:596	arg1	templates					598:606	Single viral templates	585:606	Single viral templates from blood plasma and genital tract RNA and DNA	585:654	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	8	95	theme	N-linked	1600:1607	arg1	sites					1623:1627	fewer N-linked glycosylation sites	1594:1627	fewer N-linked glycosylation sites	1594:1627	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	12	96	theme	males	2264:2268	arg1	viruses					2285:2291	the males' genital tract viruses	2260:2291	the males' genital tract viruses	2260:2291	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	11	97	theme	viral	2074:2078	arg1	characteristics					2080:2094	the viral characteristics	2070:2094	the viral characteristics associated with transmission	2070:2123	Identification of the viral characteristics associated with transmission would facilitate vaccine design.
30996101	10	98	theme	cell-free	1875:1883	arg1	virus					1891:1895	cell-free blood virus	1875:1895	cell-free blood virus	1875:1895	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	1	99	from	characteristics	241:255	arg1	males					291:295	males	291:295	males	291:295	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	100	theme	immunodeficiency	190:205	arg1	type					213:216	human immunodeficiency virus type 1	184:218	human immunodeficiency virus type 1 (HIV-1)	184:226	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	100	theme	immunodeficiency	190:205	arg1	HIV-1					221:225	HIV-1	221:225	HIV-1	221:225	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	6	101	theme	viral	1276:1280	arg1	clades					1282:1287	viral clades	1276:1287	viral clades	1276:1287	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	12	102	from	study	2163:2167	arg1	partners					2240:2247	their seroconverting female partners	2212:2247	their seroconverting female partners	2212:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	12	102	from	study	2163:2167	arg1	males					2202:2206	transmitting males	2189:2206	transmitting males	2189:2206	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	1	103	theme	type	213:216	arg1	transmission					168:179	the transmission	164:179	the transmission of human immunodeficiency virus type 1 (HIV-1)	164:226	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	8	104	gly	glycosylation	1609:1621	arg2	sites					1623:1627	fewer N-linked glycosylation sites	1594:1627	fewer N-linked glycosylation sites	1594:1627	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	6	105	theme	male	1198:1201	arg1	partner					1203:1209	their transmitting male partner	1179:1209	their transmitting male partner	1179:1209	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	6	106	theme	number	1266:1271	arg1	detection					1243:1251	detection	1243:1251	detection of a greater number of viral clades in the blood	1243:1300	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	8	107	theme	distinct	1433:1440	arg1	signatures					1453:1462	No distinct amino acid signatures	1430:1462	No distinct amino acid signatures in the men's viruses	1430:1483	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	14	108	theme	vaccine	2575:2581	arg1	responses					2583:2591	targeting vaccine responses	2565:2591	targeting vaccine responses to variants found in blood	2565:2618	These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.
30996101	12	109	theme	genital	2271:2277	arg1	tract					2279:2283	genital tract	2271:2283	the males' genital tract viruses	2260:2291	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	13	110	theme	genital	2423:2429	arg1	tract					2431:2435	genital tract	2423:2435	genital tract	2423:2435	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	0	111	from	Fluids	90:95	arg1	Comparisons					0:10	Comparisons	0:10	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.	0:141	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	4	112	theme	viral	732:736	arg1	sequences					738:746	viral sequences	732:746	viral sequences from both tissues	732:764	Eight of 29 couples examined yielded viral sequences from both tissues.
30996101	3	113	theme	genital	630:636	arg1	tract					638:642	genital tract RNA and DNA	630:654	genital tract RNA and DNA	630:654	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	6	114	theme	median	1002:1007	arg1	distance					1017:1024	The median genetic distance	998:1024	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses	998:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	2	115	theme	genital	513:519	arg1	specimens					521:529	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens	387:529	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission	387:569	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	5	116	theme	these	779:783	arg1	Analysis					767:774	Analysis	767:774	Analysis of these couples' sequences	767:802	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	5	117	theme	single	895:900	arg1	variant					908:914	a single viral variant	893:914	a single viral variant	893:914	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	8	118	theme	amino	1442:1446	arg1	signatures					1453:1462	No distinct amino acid signatures	1430:1462	No distinct amino acid signatures in the men's viruses	1430:1483	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	14	119	located	found	2605:2609	arg2	variants					2596:2603	variants	2596:2603	variants found in blood	2596:2618	These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.
30996101	14	119	located	found	2605:2609	arg1	blood					2614:2618	blood	2614:2618	blood	2614:2618	These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.
30996101	12	120	from	partners	2240:2247	arg1	study					2163:2167	This study	2158:2167	This study of HIV strains from transmitting males and their seroconverting female partners	2158:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	12	120	from	partners	2240:2247	arg1	strains					2176:2182	HIV strains	2172:2182	HIV strains from transmitting males and their seroconverting female partners	2172:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	5	121	theme	CXCR4	950:954	arg1	variants					956:963	CXCR4 variants	950:963	CXCR4 variants	950:963	Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males.
30996101	12	122	theme	seroconverting	2218:2231	arg1	partners					2240:2247	their seroconverting female partners	2212:2247	their seroconverting female partners	2212:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	1	123	theme	founding	335:342	arg1	population					350:359	the imputed founding virus population	323:359	the imputed founding virus population in their female partners	323:384	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	124	theme	virus	207:211	arg1	type					213:216	human immunodeficiency virus type 1	184:218	human immunodeficiency virus type 1 (HIV-1)	184:226	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	1	124	theme	virus	207:211	arg1	HIV-1					221:225	HIV-1	221:225	HIV-1	221:225	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	4	125	from	tissues	758:764	arg1	sequences					738:746	viral sequences	732:746	viral sequences from both tissues	732:764	Eight of 29 couples examined yielded viral sequences from both tissues.
30996101	6	126	theme	common	1053:1058	arg1	ancestor					1060:1067	the imputed most recent common ancestor	1029:1067	the imputed most recent common ancestor of the women's founder viruses	1029:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	0	127	theme	Transmission	129:140	arg1	Time					106:109	the Time	102:109	the Time of Male-to-Female Transmission	102:140	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	0	128	theme	Immunodeficiency	21:36	arg1	Type					44:47	Human Immunodeficiency Virus Type 1	15:49	Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids	15:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	2	129	theme	African	425:431	arg1	specimens					521:529	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens	387:529	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission	387:569	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	12	130	theme	HIV	2172:2174	arg1	strains					2176:2182	HIV strains	2172:2182	HIV strains from transmitting males and their seroconverting female partners	2172:2247	This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants.
30996101	3	131	from	plasma	619:624	arg1	templates					598:606	Single viral templates	585:606	Single viral templates from blood plasma and genital tract RNA and DNA	585:654	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	0	132	theme	Type	44:47	arg1	Variants					60:67	Human Immunodeficiency Virus Type 1 Envelope Variants	15:67	Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids	15:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	1	133	theme	viruses	278:284	arg1	characteristics					241:255	the genetic characteristics	229:255	the genetic characteristics of blood and genital viruses from males	229:295	To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners.
30996101	0	134	theme	Envelope	51:58	arg1	Variants					60:67	Human Immunodeficiency Virus Type 1 Envelope Variants	15:67	Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids	15:95	Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.
30996101	13	135	theme	founder	2351:2357	arg1	similar					2393:2399	similar	2393:2399	similar	2393:2399	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	13	135	theme	founder	2351:2357	arg1	viruses					2359:2365	The imputed founder viruses	2339:2365	The imputed founder viruses in women	2339:2374	The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages.
30996101	14	136	theme	tract	2660:2664	arg1	variants					2666:2673	genital tract variants	2652:2673	genital tract variants	2652:2673	These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.
30996101	2	137	theme	male-to-female	465:478	arg1	transmission					486:497	sequence-confirmed male-to-female HIV-1 transmission	446:497	sequence-confirmed male-to-female HIV-1 transmission	446:497	Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied.
30996101	8	138	contain	have	1563:1566	arg2	loops					1585:1589	shorter variable loops	1568:1589	shorter variable loops	1568:1589	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	8	138	contain	have	1563:1566	arg1	signatures					1453:1462	No distinct amino acid signatures	1430:1462	No distinct amino acid signatures in the men's viruses	1430:1483	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	8	138	contain	have	1563:1566	arg2	sequences					1553:1561	the women's env sequences	1537:1561	the women's env sequences	1537:1561	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	8	138	contain	have	1563:1566	arg2	sites					1623:1627	fewer N-linked glycosylation sites	1594:1627	fewer N-linked glycosylation sites	1594:1627	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
30996101	3	139	theme	HIV-1	678:682	arg1	gp160					688:692	HIV-1 env gp160	678:692	HIV-1 env gp160	678:692	Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160.
30996101	6	140	theme	founder	1084:1090	arg1	viruses					1092:1098	the women's founder viruses	1072:1098	the women's founder viruses	1072:1098	The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood.
30996101	10	141	theme	Mucosal	1984:1990	arg1	transmissions					1992:2004	semen.IMPORTANCE Mucosal transmissions	1967:2004	semen.IMPORTANCE Mucosal transmissions	1967:2004	The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections.
30996101	8	142	theme	shorter	1568:1574	arg1	loops					1585:1589	shorter variable loops	1568:1589	shorter variable loops	1568:1589	No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites.
31467904	7	0	theme	95	1223:1224	arg1	%					1225:1225	%	1225:1225	%	1225:1225	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	8	1	theme	A.	1374:1375	arg1	vera					1377:1380	A. vera	1374:1380	A. vera	1374:1380	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	1	2	theme	vera	415:418	arg1	leaf					420:423	A. vera leaf	412:423	A. vera leaf	412:423	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	4	3	theme	hyphae	829:834	arg1	formation					836:844	hyphae formation	829:844	hyphae formation	829:844	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	6	4	theme	phosphomolybdenum	1170:1186	arg1	assay					1196:1200	phosphomolybdenum complex assay	1170:1200	phosphomolybdenum complex assay	1170:1200	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	6	5	theme	phenolics	1061:1069	arg1	content					1071:1077	the highest total phenolics content	1043:1077	the highest total phenolics content 332.4 ±	1043:1085	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	0	6	theme	home	175:178	arg1	acceptance					148:157	acceptance	148:157	acceptance	148:157	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	6	theme	home	175:178	arg1	source					187:192	an excellent home remedy source	162:192	an excellent home remedy source in Asia and the world	162:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	4	7	theme	inhibition	846:855	arg1	assay					857:861	inhibition assay	846:861	inhibition assay	846:861	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	9	8	theme	cytotoxic	1669:1677	arg1	potential					1728:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential	1657:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant	1657:1750	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	10	9	theme	more	1769:1772	arg1	studies					1774:1780	more studies	1769:1780	more studies	1769:1780	Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.
31467904	6	10	theme	25.815μg	1140:1147	arg1	AAE/mg					1149:1154	150.4 ± 25.815μg AAE/mg	1132:1154	150.4 ± 25.815μg AAE/mg	1132:1154	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	5	11	contain	possess	916:922	arg2	contents					965:972	potential total phenolics and flavonoids contents	924:972	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	5	11	contain	possess	916:922	arg2	activities					1008:1017	significant biological activities	985:1017	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	5	11	contain	possess	916:922	arg1	AV7					911:913	AV3 to AV7	904:913	AV3 to AV7	904:913	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	5	11	contain	possess	916:922	arg1	fractions					893:901	Five fractions	888:901	Five fractions (AV3 to AV7)	888:914	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	9	12	theme	antileishmanial	1680:1694	arg1	potential					1728:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential	1657:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant	1657:1750	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	8	13	theme	fractions	1433:1441	arg1	AV1					1443:1445	three fractions AV1	1427:1445	three fractions AV1	1427:1445	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	1	14	theme	kinase	357:362	arg1	inhibition					364:373	protein kinase inhibition	349:373	protein kinase inhibition	349:373	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	9	15	theme	antibacterial	1697:1709	arg1	potential					1728:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential	1657:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant	1657:1750	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	4	16	theme	Well-known	702:711	arg1	compounds					713:721	Well-known compounds	702:721	Well-known compounds of A. vera	702:732	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	9	17	contain	contains	1574:1581	arg2	anthrones					1599:1607	anthrones	1599:1607	anthrones	1599:1607	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	9	17	contain	contains	1574:1581	arg2	anthraquinones					1583:1596	anthraquinones	1583:1596	anthraquinones	1583:1596	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	9	17	contain	contains	1574:1581	arg1	vera					1569:1572	A. vera	1566:1572	A. vera	1566:1572	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	9	17	contain	contains	1574:1581	arg2	polysaccharides					1625:1639	polysaccharides	1625:1639	polysaccharides	1625:1639	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	9	17	contain	contains	1574:1581	arg2	chromones					1610:1618	chromones	1610:1618	chromones	1610:1618	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	3	18	theme	Phenolics	552:560	arg1	composition					562:572	Phenolics composition	552:572	Phenolics composition	552:572	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	1	19	theme	different	389:397	arg1	fractions					399:407	different fractions	389:407	different fractions of A. vera leaf	389:423	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	7	20	theme	brine	1301:1305	arg1	shrimp					1307:1312	brine shrimp	1301:1312	brine shrimp lethality assay	1301:1328	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	0	21	theme	Kinase	51:56	arg1	Potential					69:77	Protein Kinase Inhibition Potential	43:77	Protein Kinase Inhibition Potential	43:77	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	21	theme	Kinase	51:56	arg1	Antimicrobial					13:25	Antimicrobial	13:25	Antimicrobial	13:25	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	21	theme	Kinase	51:56	arg1	Antioxidant					0:10	Antioxidant	0:10	Antioxidant	0:10	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	21	theme	Kinase	51:56	arg1	Cytotoxic					28:36	Cytotoxic	28:36	Cytotoxic	28:36	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	21	theme	Kinase	51:56	arg1	plant					126:130	a multifunctional plant	108:130	a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world	108:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	1	22	theme	in	291:292	arg1	antioxidant					300:310	in vitro antioxidant	291:310	in vitro antioxidant	291:310	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	2	23	theme	vera	451:454	arg1	extract					437:443	Methanolic extract	426:443	Methanolic extract of A. vera	426:454	Methanolic extract of A. vera leaves was fractionated using column chromatography and ten fractions (AV1-AV10) were obtained.
31467904	5	24	dep	AV7	911:913	arg1	to					908:909	to	908:909	to	908:909	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	7	25	theme	%	1225:1225	arg1	effect					1243:1248	95% antileishmanial effect	1223:1248	95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL	1223:1296	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	1	26	theme	antioxidant	300:310	arg1	activities					375:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	8	27	dep	21±0.5mm	1521:1528	arg1	up					1515:1516	up	1515:1516	up	1515:1516	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	0	28	from	Antioxidant	0:10	arg1	vera					100:103	Aloe vera L. Aloe vera	82:103	Aloe vera L. Aloe vera	82:103	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	4	29	theme	in	748:749	arg1	study					758:762	in silico study	748:762	in silico study against enzymes involved in brine shrimp and antileishmanial	748:823	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	1	30	theme	antimicrobial	313:325	arg1	activities					375:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	5	31	theme	phenolics	940:948	arg1	contents					965:972	potential total phenolics and flavonoids contents	924:972	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	7	32	theme	Fraction	1203:1210	arg1	AV6					1212:1214	Fraction AV6	1203:1214	Fraction AV6	1203:1214	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	1	33	theme	antileishmanial	328:342	arg1	activities					375:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	5	34	theme	flavonoids	954:963	arg1	contents					965:972	potential total phenolics and flavonoids contents	924:972	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	8	35	theme	inhibition	1504:1513	arg1	zone					1496:1499	the highest zone	1484:1499	the highest zone of inhibition up to 21±0.5mm (AV7)	1484:1534	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	0	36	theme	Inhibition	58:67	arg1	Potential					69:77	Protein Kinase Inhibition Potential	43:77	Protein Kinase Inhibition Potential	43:77	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	36	theme	Inhibition	58:67	arg1	Antimicrobial					13:25	Antimicrobial	13:25	Antimicrobial	13:25	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	36	theme	Inhibition	58:67	arg1	Antioxidant					0:10	Antioxidant	0:10	Antioxidant	0:10	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	36	theme	Inhibition	58:67	arg1	Cytotoxic					28:36	Cytotoxic	28:36	Cytotoxic	28:36	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	36	theme	Inhibition	58:67	arg1	plant					126:130	a multifunctional plant	108:130	a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world	108:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	4	37	theme	vera	729:732	arg1	compounds					713:721	Well-known compounds	702:721	Well-known compounds of A. vera	702:732	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	6	38	theme	total	1055:1059	arg1	content					1071:1077	the highest total phenolics content	1043:1077	the highest total phenolics content 332.4 ±	1043:1085	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	5	39	theme	potential	924:932	arg1	contents					965:972	potential total phenolics and flavonoids contents	924:972	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	7	40	theme	shrimp	1307:1312	arg1	lethality					1314:1322	brine shrimp lethality	1301:1322	brine shrimp lethality assay	1301:1328	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	3	41	theme	protein	624:630	arg1	activities					650:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	2	42	theme	Methanolic	426:435	arg1	extract					437:443	Methanolic extract	426:443	Methanolic extract of A. vera	426:454	Methanolic extract of A. vera leaves was fractionated using column chromatography and ten fractions (AV1-AV10) were obtained.
31467904	0	43	from	source	187:192	arg1	Asia					197:200	Asia	197:200	Asia	197:200	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	43	from	source	187:192	arg1	world					210:214	the world	206:214	the world	206:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	10	44	theme	drug	1840:1843	arg1	development					1845:1855	drug development	1840:1855	drug development	1840:1855	Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.
31467904	7	45	theme	LD50	1272:1275	arg1	value					1277:1281	the lowest LD50 value	1261:1281	95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL	1223:1296	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	3	46	theme	inhibition	639:648	arg1	activities					650:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	5	47	theme	significant	985:995	arg1	activities					1008:1017	significant biological activities	985:1017	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	0	48	from	vera	100:103	arg1	Antimicrobial					13:25	Antimicrobial	13:25	Antimicrobial	13:25	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	48	from	vera	100:103	arg1	Potential					69:77	Protein Kinase Inhibition Potential	43:77	Protein Kinase Inhibition Potential	43:77	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	48	from	vera	100:103	arg1	Antioxidant					0:10	Antioxidant	0:10	Antioxidant	0:10	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	48	from	vera	100:103	arg1	Cytotoxic					28:36	Cytotoxic	28:36	Cytotoxic	28:36	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	48	from	vera	100:103	arg1	plant					126:130	a multifunctional plant	108:130	a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world	108:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	4	49	dep	results	879:885	arg1	the					866:868	the	866:868	the	866:868	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	4	49	dep	results	879:885	arg1	basis					870:874	basis	870:874	basis	870:874	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	1	50	from	contents	278:285	arg1	fractions					399:407	different fractions	389:407	different fractions of A. vera leaf	389:423	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	4	51	used	used	739:742	arg2	compounds					713:721	Well-known compounds	702:721	Well-known compounds of A. vera	702:732	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	6	52	theme	±	1085:1085	arg1	content					1071:1077	the highest total phenolics content	1043:1077	the highest total phenolics content 332.4 ±	1043:1085	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	0	53	theme	excellent	165:173	arg1	acceptance					148:157	acceptance	148:157	acceptance	148:157	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	53	theme	excellent	165:173	arg1	source					187:192	an excellent home remedy source	162:192	an excellent home remedy source in Asia and the world	162:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	1	54	theme	A.	412:413	arg1	leaf					420:423	A. vera leaf	412:423	A. vera leaf	412:423	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	1	55	theme	present	221:227	arg1	study					229:233	The present study	217:233	The present study	217:233	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	6	56	theme	complex	1188:1194	arg1	assay					1196:1200	phosphomolybdenum complex assay	1170:1200	phosphomolybdenum complex assay	1170:1200	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	0	57	theme	remedy	180:185	arg1	acceptance					148:157	acceptance	148:157	acceptance	148:157	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	57	theme	remedy	180:185	arg1	source					187:192	an excellent home remedy source	162:192	an excellent home remedy source in Asia and the world	162:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	1	58	theme	leaf	420:423	arg1	fractions					399:407	different fractions	389:407	different fractions of A. vera leaf	389:423	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	9	59	theme	responsible	1641:1651	arg1	anthraquinones					1583:1596	anthraquinones	1583:1596	anthraquinones	1583:1596	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	9	60	theme	plant	1746:1750	arg1	potential					1728:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential	1657:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant	1657:1750	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	9	61	theme	synergistic	1657:1667	arg1	potential					1728:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential	1657:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant	1657:1750	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	6	62	theme	±	1138:1138	arg1	AAE/mg					1149:1154	150.4 ± 25.815μg AAE/mg	1132:1154	150.4 ± 25.815μg AAE/mg	1132:1154	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	0	63	theme	multifunctional	110:124	arg1	Antimicrobial					13:25	Antimicrobial	13:25	Antimicrobial	13:25	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	63	theme	multifunctional	110:124	arg1	Potential					69:77	Protein Kinase Inhibition Potential	43:77	Protein Kinase Inhibition Potential	43:77	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	63	theme	multifunctional	110:124	arg1	Antioxidant					0:10	Antioxidant	0:10	Antioxidant	0:10	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	63	theme	multifunctional	110:124	arg1	Cytotoxic					28:36	Cytotoxic	28:36	Cytotoxic	28:36	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	0	63	theme	multifunctional	110:124	arg1	plant					126:130	a multifunctional plant	108:130	a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world	108:214	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	1	64	theme	protein	349:355	arg1	inhibition					364:373	protein kinase inhibition	349:373	protein kinase inhibition	349:373	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	3	65	theme	composition	562:572	arg1	activities					650:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	5	66	dep	along	974:978	arg1	with					980:983	with	980:983	with	980:983	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	1	67	theme	inhibition	364:373	arg1	activities					375:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	291:384	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	3	68	theme	antimicrobial	588:600	arg1	activities					650:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	5	69	theme	AV3	904:906	arg1	AV7					911:913	AV3 to AV7	904:913	AV3 to AV7	904:913	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	5	69	theme	AV3	904:906	arg1	fractions					893:901	Five fractions	888:901	Five fractions (AV3 to AV7)	888:914	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	6	70	theme	AV4	1020:1022	arg1	fraction					1024:1031	AV4 fraction	1020:1031	AV4 fraction	1020:1031	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	9	71	theme	antioxidant	1716:1726	arg1	potential					1728:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential	1657:1736	synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant	1657:1750	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	8	72	theme	Kinase	1343:1348	arg1	potential					1361:1369	The Protein Kinase inhibition potential	1331:1369	The Protein Kinase inhibition potential in A. vera	1331:1380	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	7	73	theme	lowest	1265:1270	arg1	value					1277:1281	the lowest LD50 value	1261:1281	95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL	1223:1296	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	7	74	theme	antileishmanial	1227:1241	arg1	effect					1243:1248	95% antileishmanial effect	1223:1248	95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL	1223:1296	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	3	75	theme	antioxidant	575:585	arg1	activities					650:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	4	76	dep	study	758:762	arg1	assay					857:861	inhibition assay	846:861	inhibition assay	846:861	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	1	77	from	activities	375:384	arg1	fractions					399:407	different fractions	389:407	different fractions of A. vera leaf	389:423	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	4	78	dep	in	748:749	arg1	silico					751:756	silico	751:756	silico	751:756	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	2	79	theme	A.	448:449	arg1	vera					451:454	A. vera	448:454	A. vera	448:454	Methanolic extract of A. vera leaves was fractionated using column chromatography and ten fractions (AV1-AV10) were obtained.
31467904	8	80	theme	highest	1488:1494	arg1	zone					1496:1499	the highest zone	1484:1499	the highest zone of inhibition up to 21±0.5mm (AV7)	1484:1534	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	5	81	theme	total	934:938	arg1	contents					965:972	potential total phenolics and flavonoids contents	924:972	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	2	82	theme	column	486:491	arg1	chromatography					493:506	column chromatography	486:506	column chromatography	486:506	Methanolic extract of A. vera leaves was fractionated using column chromatography and ten fractions (AV1-AV10) were obtained.
31467904	8	83	theme	Protein	1335:1341	arg1	potential					1361:1369	The Protein Kinase inhibition potential	1331:1369	The Protein Kinase inhibition potential in A. vera	1331:1380	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	6	84	theme	total	1105:1109	arg1	activity					1123:1130	total antioxidant activity	1105:1130	total antioxidant activity	1105:1130	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	0	85	theme	Aloe	95:98	arg1	vera					100:103	Aloe vera L. Aloe vera	82:103	Aloe vera L. Aloe vera	82:103	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	6	86	theme	332.4	1079:1083	arg1	±					1085:1085	±	1085:1085	±	1085:1085	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	8	87	theme	inhibition	1350:1359	arg1	potential					1361:1369	The Protein Kinase inhibition potential	1331:1369	The Protein Kinase inhibition potential in A. vera	1331:1380	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	7	88	theme	lethality	1314:1322	arg1	assay					1324:1328	brine shrimp lethality assay	1301:1328	brine shrimp lethality assay	1301:1328	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	4	89	theme	A.	726:727	arg1	vera					729:732	A. vera	726:732	A. vera	726:732	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	9	90	theme	Docking	1537:1543	arg1	analysis					1545:1552	Docking analysis	1537:1552	Docking analysis	1537:1552	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	10	91	theme	A.	1783:1784	arg1	vera					1786:1789	A. vera	1783:1789	A. vera	1783:1789	Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.
31467904	6	92	theme	highest	1047:1053	arg1	content					1071:1077	the highest total phenolics content	1043:1077	the highest total phenolics content 332.4 ±	1043:1085	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	1	93	dep	in	291:292	arg1	vitro					294:298	vitro	294:298	vitro	294:298	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	5	94	theme	biological	997:1006	arg1	activities					1008:1017	significant biological activities	985:1017	potential total phenolics and flavonoids contents along with significant biological activities	924:1017	Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities.
31467904	7	95	theme	0.5305μg/mL	1286:1296	arg1	value					1277:1281	the lowest LD50 value	1261:1281	95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL	1223:1296	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	7	95	theme	0.5305μg/mL	1286:1296	arg1	effect					1243:1248	95% antileishmanial effect	1223:1248	95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL	1223:1296	Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305μg/mL in brine shrimp lethality assay.
31467904	3	96	theme	antileishmanial	603:617	arg1	activities					650:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	4	97	theme	brine	792:796	arg1	shrimp					798:803	brine shrimp	792:803	brine shrimp	792:803	Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results.
31467904	0	98	theme	Protein	43:49	arg1	Kinase					51:56	Protein Kinase	43:56	Protein Kinase Inhibition Potential	43:77	Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L. Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world.
31467904	1	99	theme	phytochemical	264:276	arg1	contents					278:285	the phytochemical contents	260:285	the phytochemical contents	260:285	The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf.
31467904	9	100	theme	A.	1566:1567	arg1	vera					1569:1572	A. vera	1566:1572	A. vera	1566:1572	Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant.
31467904	10	101	contain	have	1806:1809	arg2	potential					1815:1823	the potential to be used for drug development	1811:1855	the potential to be used for drug development	1811:1855	Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.
31467904	10	101	contain	have	1806:1809	arg1	vera					1786:1789	A. vera	1783:1789	A. vera	1783:1789	Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.
31467904	6	102	dep	GAE/mg	1094:1099	arg1	AAE/mg					1149:1154	150.4 ± 25.815μg AAE/mg	1132:1154	150.4 ± 25.815μg AAE/mg	1132:1154	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	8	103	from	potential	1361:1369	arg1	vera					1377:1380	A. vera	1374:1380	A. vera	1374:1380	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	6	104	theme	antioxidant	1111:1121	arg1	activity					1123:1130	total antioxidant activity	1105:1130	total antioxidant activity	1105:1130	AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6μg GAE/mg and total antioxidant activity 150.4 ± 25.815μg AAE/mg determined by phosphomolybdenum complex assay.
31467904	3	105	theme	kinase	632:637	arg1	activities					650:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities	552:659	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31467904	8	106	theme	first	1412:1416	arg1	time					1418:1421	the first time	1408:1421	the first time	1408:1421	The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7).
31467904	3	107	theme	standard	682:689	arg1	protocols					691:699	standard protocols	682:699	standard protocols	682:699	Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols.
31455637	4	0	theme	mammalian	896:904	arg1	transition					906:915	the mammalian transition	892:915	the mammalian transition from insectivory to herbivory	892:945	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	8	1	theme	genomic	1494:1500	arg1	sequences					1521:1529	genomic and transcriptomic sequences	1494:1529	genomic and transcriptomic sequences	1494:1529	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	6	2	theme	Comparative	1171:1181	arg1	genomics					1183:1190	Comparative genomics	1171:1190	Comparative genomics	1171:1190	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	3	3	dep	sequences	563:571	arg1	characterize					645:656	characterize	645:656	characterize gene gain/loss patterns associated with their evolution	645:712	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	3	3	dep	sequences	563:571	arg1	time					618:621	time	618:621	time	618:621	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	3	3	dep	sequences	563:571	arg1	explore					576:582	explore	576:582	explore	576:582	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	13	4	theme	rumen	2384:2388	arg1	fungi					2390:2394	The rumen fungi	2380:2394	The rumen fungi	2380:2394	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	7	5	theme	third	1353:1357	arg1	lyase					1397:1401	plant-like polysaccharide lyase	1371:1401	plant-like polysaccharide lyase	1371:1401	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	7	5	theme	third	1353:1357	arg1	domain					1363:1368	A third AGF domain	1351:1368	A third AGF domain	1351:1368	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	8	6	theme	transcriptomic	1506:1519	arg1	sequences					1521:1529	genomic and transcriptomic sequences	1494:1529	genomic and transcriptomic sequences	1494:1529	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	8	7	theme	lineage-specific	1583:1598	arg1	genes					1600:1604	these lineage-specific genes	1577:1604	these lineage-specific genes	1577:1604	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	2	8	dep	84	468:469	arg1	to					465:466	to	465:466	to	465:466	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	9	9	theme	rumen	1760:1764	arg1	microbes					1766:1773	the rumen microbes	1756:1773	the rumen microbes	1756:1773	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	15	10	theme	polysaccharide	2785:2798	arg1	lyase					2800:2804	a plant-like polysaccharide lyase	2772:2804	a plant-like polysaccharide lyase	2772:2804	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	15	10	theme	polysaccharide	2785:2798	arg1	one					2765:2767	one	2765:2767	one	2765:2767	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	9	11	theme	hosts.IMPORTANCE	1786:1801	arg1	fungi					1813:1817	animal hosts.IMPORTANCE Anaerobic fungi	1779:1817	animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals	1779:1860	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	5	12	theme	herbivory	1065:1073	arg1	transition					1075:1084	mammalian herbivory transition	1055:1084	mammalian herbivory transition	1055:1084	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	0	13	theme	Molecular	0:8	arg1	Dating					10:15	Molecular Dating	0:15	Molecular Dating of the Emergence of Anaerobic Rumen Fungi	0:57	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	13	14	theme	fungal	2614:2619	arg1	genomes					2621:2627	1,000 fungal genomes	2608:2627	1,000 fungal genomes	2608:2627	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	14	15	theme	gene	2740:2743	arg1	transfer					2745:2752	horizontal gene transfer	2729:2752	horizontal gene transfer	2729:2752	Two of these domains were likely acquired from rumen gut bacteria and animal hosts separately via horizontal gene transfer.
31455637	10	16	theme	gut	2008:2010	arg1	fungi					2012:2016	these poorly characterized anaerobic gut fungi	1971:2016	these poorly characterized anaerobic gut fungi	1971:2016	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	9	17	contain	possess	1862:1868	arg1	fungi					1813:1817	animal hosts.IMPORTANCE Anaerobic fungi	1779:1817	animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals	1779:1860	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	9	17	contain	possess	1862:1868	arg2	ability					1887:1893	an extraordinary ability	1870:1893	an extraordinary ability to degrade plant biomass	1870:1918	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	8	18	theme	all	1616:1618	arg1	clades					1624:1629	nearly all AGF clades	1609:1629	nearly all AGF clades	1609:1629	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	13	19	theme	protein	2452:2458	arg1	domains					2460:2466	three protein domains	2446:2466	three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes)	2446:2628	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	15	20	theme	potential	2848:2856	arg1	abilities					2875:2883	potential pectin breakdown abilities	2848:2883	potential pectin breakdown abilities	2848:2883	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	5	21	from	materials	1160:1168	arg1	efficiency					1103:1112	the efficiency	1099:1112	the efficiency of energy acquisition from recalcitrant plant materials	1099:1168	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	4	22	theme	time	814:817	arg1	frame					819:823	a time frame	812:823	a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory	812:945	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	11	23	theme	mammals	2233:2239	arg1	concurrence					2122:2132	remarkable concurrence	2111:2132	remarkable concurrence of the divergence times of the rumen fungi	2111:2175	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	11	23	theme	mammals	2233:2239	arg1	shift					2214:2218	the dietary shift	2202:2218	the dietary shift of ancestral mammals from primarily insectivory to herbivory	2202:2279	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	11	23	theme	mammals	2233:2239	arg1	grasses					2189:2195	the forage grasses	2178:2195	the forage grasses	2178:2195	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	15	24	theme	pectin	2858:2863	arg1	abilities					2875:2883	potential pectin breakdown abilities	2848:2883	potential pectin breakdown abilities	2848:2883	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	5	25	theme	transition	1075:1084	arg1	success					1044:1050	the success	1040:1050	the success of mammalian herbivory transition	1040:1084	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	3	26	theme	AGF	498:500	arg1	transcriptomes					502:515	21 AGF transcriptomes	495:515	21 AGF transcriptomes	495:515	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	9	27	theme	herbivorous	1842:1852	arg1	mammals					1854:1860	herbivorous mammals	1842:1860	herbivorous mammals	1842:1860	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	13	28	from	functions	2482:2490	arg1	degradation					2508:2518	plant pectin degradation	2495:2518	plant pectin degradation	2495:2518	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	13	28	from	functions	2482:2490	arg1	defense					2534:2540	microbial defense	2524:2540	microbial defense	2524:2540	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	6	29	theme	lineage-specific	1212:1227	arg1	genes					1229:1233	multiple lineage-specific genes	1203:1233	multiple lineage-specific genes	1203:1233	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	4	30	dep	66	784:785	arg1	±10					788:790	±10	788:790	±10	788:790	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	15	31	theme	fungal	2829:2834	arg1	enzyme					2836:2841	a unique fungal enzyme	2820:2841	a unique fungal enzyme with potential pectin breakdown abilities	2820:2883	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	14	32	theme	gut	2684:2686	arg1	bacteria					2688:2695	rumen gut bacteria	2678:2695	rumen gut bacteria	2678:2695	Two of these domains were likely acquired from rumen gut bacteria and animal hosts separately via horizontal gene transfer.
31455637	8	33	dep	presence	1550:1557	arg1	the					1546:1548	the	1546:1548	the	1546:1548	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	1	34	theme	gut	117:119	arg1	AGF					128:130	AGF	128:130	AGF	128:130	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	1	34	theme	gut	117:119	arg1	fungi					121:125	The anaerobic gut fungi	103:125	The anaerobic gut fungi (AGF)	103:131	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	9	35	theme	extraordinary	1873:1885	arg1	ability					1887:1893	an extraordinary ability	1870:1893	an extraordinary ability to degrade plant biomass	1870:1918	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	0	36	theme	Fungi	53:57	arg1	Emergence					24:32	the Emergence	20:32	the Emergence of Anaerobic Rumen Fungi	20:57	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	1	37	theme	fiber	283:287	arg1	degradation					262:272	the degradation	258:272	the degradation of plant fiber	258:287	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	9	38	theme	AGF	1702:1704	arg1	abilities					1689:1697	the exceptional abilities	1673:1697	the exceptional abilities of AGF	1673:1704	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	7	39	theme	aids	1454:1457	arg1	AGF					1459:1461	aids AGF	1454:1461	aids AGF	1454:1461	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	4	40	theme	grasses	862:868	arg1	evolution					849:857	the evolution	845:857	the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory	845:945	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	13	41	theme	other	2570:2574	arg1	organisms					2583:2591	all other fungal organisms	2566:2591	all other fungal organisms (examined over 1,000 fungal genomes)	2566:2628	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	2	42	theme	AT-biased	451:459	arg1	genomes					473:479	their large (up to 200 Mb) and AT-biased (78 to 84%) genomes	420:479	their large (up to 200 Mb) and AT-biased (78 to 84%) genomes	420:479	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	9	43	theme	plant	1906:1910	arg1	biomass					1912:1918	plant biomass	1906:1918	plant biomass	1906:1918	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	5	44	theme	plant	1154:1158	arg1	materials					1160:1168	recalcitrant plant materials	1141:1168	recalcitrant plant materials	1141:1168	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	11	45	theme	times	2152:2156	arg1	concurrence					2122:2132	remarkable concurrence	2111:2132	remarkable concurrence of the divergence times of the rumen fungi	2111:2175	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	11	45	theme	times	2152:2156	arg1	shift					2214:2218	the dietary shift	2202:2218	the dietary shift of ancestral mammals from primarily insectivory to herbivory	2202:2279	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	11	45	theme	times	2152:2156	arg1	grasses					2189:2195	the forage grasses	2178:2195	the forage grasses	2178:2195	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	0	46	theme	Acquired	87:94	arg1	Genes					96:100	Laterally Acquired Genes	77:100	Laterally Acquired Genes	77:100	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	5	47	theme	independent	967:977	arg1	estimations					979:989	independent estimations	967:989	independent estimations	967:989	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	9	48	theme	exceptional	1677:1687	arg1	abilities					1689:1697	the exceptional abilities	1673:1697	the exceptional abilities of AGF	1673:1704	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	2	49	theme	AGF	343:345	arg1	analyses					327:334	Comparative genomic and phylogenomic analyses	290:334	Comparative genomic and phylogenomic analyses of the AGF	290:345	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	6	50	theme	gene	1330:1333	arg1	HGT					1345:1347	HGT	1345:1347	HGT	1345:1347	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	6	50	theme	gene	1330:1333	arg1	transfer					1335:1342	horizontal gene transfer	1319:1342	horizontal gene transfer (HGT)	1319:1348	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	2	51	theme	growth	391:396	arg1	condition					398:406	their fastidious growth condition	374:406	their fastidious growth condition	374:406	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	12	52	theme	Comparative	2282:2292	arg1	genomics					2294:2301	Comparative genomics	2282:2301	Comparative genomics	2282:2301	Comparative genomics identified unique machinery in these fungi to utilize plant polysaccharides.
31455637	13	53	theme	microbial	2524:2532	arg1	defense					2534:2540	microbial defense	2524:2540	microbial defense	2524:2540	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	2	54	dep	200 Mb	439:444	arg1	up					433:434	up	433:434	up	433:434	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	3	55	theme	AGF	552:554	arg1	sequences					563:571	5 available AGF genome sequences	540:571	5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution	540:712	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	6	56	theme	animal	1302:1307	arg1	hosts					1309:1313	animal hosts	1302:1313	animal hosts	1302:1313	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	0	57	theme	Emergence	24:32	arg1	Impact					67:72	the Impact	63:72	the Impact of Laterally Acquired Genes	63:100	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	0	57	theme	Emergence	24:32	arg1	Dating					10:15	Molecular Dating	0:15	Molecular Dating of the Emergence of Anaerobic Rumen Fungi	0:57	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	9	58	theme	plant	1717:1721	arg1	biomass					1723:1729	plant biomass	1717:1729	plant biomass	1717:1729	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	4	59	theme	recent	741:746	arg1	ancestor					755:762	the most recent common ancestor	732:762	the most recent common ancestor of the AGF	732:773	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	2	60	theme	genomic	302:308	arg1	analyses					327:334	Comparative genomic and phylogenomic analyses	290:334	Comparative genomic and phylogenomic analyses of the AGF	290:345	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	0	61	theme	Anaerobic	37:45	arg1	Fungi					53:57	Anaerobic Rumen Fungi	37:57	Anaerobic Rumen Fungi	37:57	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	6	62	from	genes	1229:1233	arg1	AGF					1242:1244	the AGF	1238:1244	the AGF	1238:1244	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	2	63	dep	large	426:430	arg1	200 Mb					439:444	200 Mb	439:444	200 Mb	439:444	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	7	64	theme	polysaccharide	1382:1395	arg1	lyase					1397:1401	plant-like polysaccharide lyase	1371:1401	plant-like polysaccharide lyase	1371:1401	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	7	64	theme	polysaccharide	1382:1395	arg1	domain					1363:1368	A third AGF domain	1351:1368	A third AGF domain	1351:1368	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	10	65	dep	data	2055:2058	arg1	both					2024:2027	both	2024:2027	both	2024:2027	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	10	65	dep	data	2055:2058	arg1	genomic					2047:2053	genomic	2047:2053	genomic	2047:2053	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	11	66	theme	Phylogenomics	2061:2073	arg1	analyses					2096:2103	Phylogenomics and molecular dating analyses	2061:2103	Phylogenomics and molecular dating analyses	2061:2103	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	1	67	dep	rumen	172:176	arg1	the					168:170	the	168:170	the	168:170	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	8	68	theme	sequences	1521:1529	arg1	Analysis					1482:1489	Analysis	1482:1489	Analysis of genomic and transcriptomic sequences	1482:1529	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	1	69	theme	alimentary	182:191	arg1	tract					193:197	alimentary tract	182:197	alimentary tract	182:197	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	11	70	from	insectivory	2256:2266	arg1	concurrence					2122:2132	remarkable concurrence	2111:2132	remarkable concurrence of the divergence times of the rumen fungi	2111:2175	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	11	70	from	insectivory	2256:2266	arg1	shift					2214:2218	the dietary shift	2202:2218	the dietary shift of ancestral mammals from primarily insectivory to herbivory	2202:2279	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	11	70	from	insectivory	2256:2266	arg1	grasses					2189:2195	the forage grasses	2178:2195	the forage grasses	2178:2195	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	10	71	theme	genomic	1948:1954	arg1	composition					1956:1966	genomic composition	1948:1966	genomic composition	1948:1966	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	10	72	theme	fungi	2012:2016	arg1	composition					1956:1966	genomic composition	1948:1966	genomic composition	1948:1966	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	10	72	theme	fungi	2012:2016	arg1	origin					1937:1942	origin	1937:1942	origin	1937:1942	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	13	73	with	domains	2460:2466	arg1	functions					2482:2490	putative functions	2473:2490	putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes)	2473:2628	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	4	74	from	evolution	849:857	arg1	insectivory					922:932	insectivory	922:932	insectivory	922:932	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	11	75	theme	dating	2089:2094	arg1	analyses					2096:2103	Phylogenomics and molecular dating analyses	2061:2103	Phylogenomics and molecular dating analyses	2061:2103	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	7	76	theme	AGF	1359:1361	arg1	lyase					1397:1401	plant-like polysaccharide lyase	1371:1401	plant-like polysaccharide lyase	1371:1401	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	7	76	theme	AGF	1359:1361	arg1	domain					1363:1368	A third AGF domain	1351:1368	A third AGF domain	1351:1368	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	10	77	dep	both	2024:2027	arg1	transcriptome					2029:2041	transcriptome	2029:2041	transcriptome	2029:2041	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	4	78	theme	transition	906:915	arg1	evolution					849:857	the evolution	845:857	the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory	845:945	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	12	79	theme	unique	2314:2319	arg1	machinery					2321:2329	unique machinery	2314:2329	unique machinery	2314:2329	Comparative genomics identified unique machinery in these fungi to utilize plant polysaccharides.
31455637	9	80	theme	genetic	1638:1644	arg1	elements					1646:1653	These genetic elements	1632:1653	These genetic elements	1632:1653	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	2	81	theme	phylogenomic	314:325	arg1	analyses					327:334	Comparative genomic and phylogenomic analyses	290:334	Comparative genomic and phylogenomic analyses of the AGF	290:345	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	1	82	theme	mammals	214:220	arg1	rumen					172:176	rumen	172:176	rumen	172:176	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	1	82	theme	mammals	214:220	arg1	tract					193:197	alimentary tract	182:197	alimentary tract	182:197	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	4	83	theme	AGF	771:773	arg1	ancestor					755:762	the most recent common ancestor	732:762	the most recent common ancestor of the AGF	732:773	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	9	84	theme	microbes	1766:1773	arg1	metabolism					1742:1751	metabolism	1742:1751	metabolism of the rumen microbes	1742:1773	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	3	85	theme	evolutionary	590:601	arg1	relationships					603:615	their evolutionary relationships	584:615	their evolutionary relationships	584:615	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	9	86	theme	animal	1779:1784	arg1	fungi					1813:1817	animal hosts.IMPORTANCE Anaerobic fungi	1779:1817	animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals	1779:1860	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	13	87	theme	plant	2495:2499	arg1	degradation					2508:2518	plant pectin degradation	2495:2518	plant pectin degradation	2495:2518	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	4	88	theme	common	748:753	arg1	ancestor					755:762	the most recent common ancestor	732:762	the most recent common ancestor of the AGF	732:773	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	9	89	theme	Anaerobic	1803:1811	arg1	fungi					1813:1817	animal hosts.IMPORTANCE Anaerobic fungi	1779:1817	animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals	1779:1860	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	15	90	with	enzyme	2836:2841	arg1	abilities					2875:2883	potential pectin breakdown abilities	2848:2883	potential pectin breakdown abilities	2848:2883	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	3	91	theme	gene	658:661	arg1	patterns					673:680	gene gain/loss patterns	658:680	gene gain/loss patterns associated with their evolution	658:712	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	8	92	theme	genes	1600:1604	arg1	expression					1563:1572	expression	1563:1572	expression	1563:1572	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	8	92	theme	genes	1600:1604	arg1	presence					1550:1557	presence	1550:1557	presence	1550:1557	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	14	93	theme	horizontal	2729:2738	arg1	transfer					2745:2752	horizontal gene transfer	2729:2752	horizontal gene transfer	2729:2752	Two of these domains were likely acquired from rumen gut bacteria and animal hosts separately via horizontal gene transfer.
31455637	3	94	theme	gain/loss	663:671	arg1	patterns					673:680	gene gain/loss patterns	658:680	gene gain/loss patterns associated with their evolution	658:712	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	15	95	theme	plant-like	2774:2783	arg1	lyase					2800:2804	a plant-like polysaccharide lyase	2772:2804	a plant-like polysaccharide lyase	2772:2804	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	15	95	theme	plant-like	2774:2783	arg1	one					2765:2767	one	2765:2767	one	2765:2767	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	13	96	theme	fungal	2576:2581	arg1	organisms					2583:2591	all other fungal organisms	2566:2591	all other fungal organisms (examined over 1,000 fungal genomes)	2566:2628	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	8	97	theme	AGF	1620:1622	arg1	clades					1624:1629	nearly all AGF clades	1609:1629	nearly all AGF clades	1609:1629	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	10	98	dep	origin	1937:1942	arg1	the					1933:1935	the	1933:1935	the	1933:1935	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	14	99	theme	animal	2701:2706	arg1	hosts					2708:2712	animal hosts	2701:2712	animal hosts	2701:2712	Two of these domains were likely acquired from rumen gut bacteria and animal hosts separately via horizontal gene transfer.
31455637	6	100	theme	genes	1229:1233	arg1	two					1247:1249	two	1247:1249	two	1247:1249	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	6	100	theme	genes	1229:1233	arg1	genes					1229:1233	multiple lineage-specific genes	1203:1233	multiple lineage-specific genes	1203:1233	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	8	101	attach	presence	1550:1557	arg1	clades					1624:1629	nearly all AGF clades	1609:1629	nearly all AGF clades	1609:1629	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	8	101	attach	presence	1550:1557	arg2	genes					1600:1604	these lineage-specific genes	1577:1604	these lineage-specific genes	1577:1604	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	13	102	from	organisms	2583:2591	arg1	absent					2554:2559	absent	2554:2559	absent	2554:2559	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	9	103	theme	mammals	1854:1860	arg1	rumen					1833:1837	the rumen	1829:1837	the rumen of herbivorous mammals	1829:1860	These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.IMPORTANCE Anaerobic fungi living in the rumen of herbivorous mammals possess an extraordinary ability to degrade plant biomass.
31455637	6	104	theme	multiple	1203:1210	arg1	genes					1229:1233	multiple lineage-specific genes	1203:1233	multiple lineage-specific genes	1203:1233	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	1	105	theme	anaerobic	107:115	arg1	AGF					128:130	AGF	128:130	AGF	128:130	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	1	105	theme	anaerobic	107:115	arg1	fungi					121:125	The anaerobic gut fungi	103:125	The anaerobic gut fungi (AGF)	103:131	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	4	106	theme	million	793:799	arg1	years					801:805	66 (±10) million years	784:805	66 (±10) million years	784:805	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	6	107	theme	gut	1285:1287	arg1	bacteria					1289:1296	rumen gut bacteria	1279:1296	rumen gut bacteria	1279:1296	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	4	108	from	insectivory	922:932	arg1	Poaceae					871:877	Poaceae	871:877	Poaceae	871:877	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	4	108	from	insectivory	922:932	arg1	evolution					849:857	the evolution	845:857	the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory	845:945	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	4	108	from	insectivory	922:932	arg1	transition					906:915	the mammalian transition	892:915	the mammalian transition from insectivory to herbivory	892:945	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	4	108	from	insectivory	922:932	arg1	grasses					862:868	grasses	862:868	grasses (Poaceae)	862:878	We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a time frame that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory.
31455637	11	109	theme	divergence	2141:2150	arg1	times					2152:2156	the divergence times	2137:2156	the divergence times of the rumen fungi	2137:2175	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	15	110	theme	unique	2822:2827	arg1	enzyme					2836:2841	a unique fungal enzyme	2820:2841	a unique fungal enzyme with potential pectin breakdown abilities	2820:2883	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	5	111	theme	acquisition	1124:1134	arg1	efficiency					1103:1112	the efficiency	1099:1112	the efficiency of energy acquisition from recalcitrant plant materials	1099:1168	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	2	112	theme	large	426:430	arg1	genomes					473:479	their large (up to 200 Mb) and AT-biased (78 to 84%) genomes	420:479	their large (up to 200 Mb) and AT-biased (78 to 84%) genomes	420:479	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	5	113	theme	recalcitrant	1141:1152	arg1	materials					1160:1168	recalcitrant plant materials	1141:1168	recalcitrant plant materials	1141:1168	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	0	114	theme	Laterally	77:85	arg1	Genes					96:100	Laterally Acquired Genes	77:100	Laterally Acquired Genes	77:100	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	11	115	theme	rumen	2165:2169	arg1	fungi					2171:2175	the rumen fungi	2161:2175	the rumen fungi	2161:2175	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	0	116	theme	Genes	96:100	arg1	Impact					67:72	the Impact	63:72	the Impact of Laterally Acquired Genes	63:100	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	0	116	theme	Genes	96:100	arg1	Dating					10:15	Molecular Dating	0:15	Molecular Dating of the Emergence of Anaerobic Rumen Fungi	0:57	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	11	117	theme	dietary	2206:2212	arg1	shift					2214:2218	the dietary shift	2202:2218	the dietary shift of ancestral mammals from primarily insectivory to herbivory	2202:2279	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	13	118	theme	pectin	2501:2506	arg1	degradation					2508:2518	plant pectin degradation	2495:2518	plant pectin degradation	2495:2518	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	5	119	theme	estimations	979:989	arg1	concordance					952:962	The concordance	948:962	The concordance of independent estimations	948:989	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	14	120	theme	domains	2644:2650	arg1	Two					2631:2633	Two	2631:2633	Two	2631:2633	Two of these domains were likely acquired from rumen gut bacteria and animal hosts separately via horizontal gene transfer.
31455637	14	120	theme	domains	2644:2650	arg1	domains					2644:2650	these domains	2638:2650	these domains	2638:2650	Two of these domains were likely acquired from rumen gut bacteria and animal hosts separately via horizontal gene transfer.
31455637	11	121	theme	molecular	2079:2087	arg1	dating					2089:2094	molecular dating	2079:2094	molecular dating	2079:2094	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	12	122	theme	plant	2357:2361	arg1	polysaccharides					2363:2377	plant polysaccharides	2357:2377	plant polysaccharides	2357:2377	Comparative genomics identified unique machinery in these fungi to utilize plant polysaccharides.
31455637	8	123	from	expression	1563:1572	arg1	clades					1624:1629	nearly all AGF clades	1609:1629	nearly all AGF clades	1609:1629	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	6	124	theme	horizontal	1319:1328	arg1	HGT					1345:1347	HGT	1345:1347	HGT	1345:1347	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	6	124	theme	horizontal	1319:1328	arg1	transfer					1335:1342	horizontal gene transfer	1319:1342	horizontal gene transfer (HGT)	1319:1348	Comparative genomics identified multiple lineage-specific genes in the AGF, two of which were acquired from rumen gut bacteria and animal hosts via horizontal gene transfer (HGT).
31455637	1	125	theme	important	239:247	arg1	roles					249:253	important roles	239:253	important roles	239:253	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	7	126	from	gene	1423:1426	arg1	fungi					1431:1435	fungi	1431:1435	fungi	1431:1435	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	2	127	theme	fastidious	380:389	arg1	condition					398:406	their fastidious growth condition	374:406	their fastidious growth condition	374:406	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	3	128	theme	available	542:550	arg1	sequences					563:571	5 available AGF genome sequences	540:571	5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution	540:712	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	8	129	from	presence	1550:1557	arg1	clades					1624:1629	nearly all AGF clades	1609:1629	nearly all AGF clades	1609:1629	Analysis of genomic and transcriptomic sequences confirmed both the presence and expression of these lineage-specific genes in nearly all AGF clades.
31455637	13	130	theme	putative	2473:2480	arg1	functions					2482:2490	putative functions	2473:2490	putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes)	2473:2628	The rumen fungi were also identified with the ability to code for three protein domains with putative functions in plant pectin degradation and microbial defense, which were absent from all other fungal organisms (examined over 1,000 fungal genomes).
31455637	5	131	theme	mammalian	1055:1063	arg1	transition					1075:1084	mammalian herbivory transition	1055:1084	mammalian herbivory transition	1055:1084	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31455637	2	132	dep	AT-biased	451:459	arg1	%					470:470	78 to 84%	462:470	78 to 84%	462:470	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	7	133	theme	novel	1417:1421	arg1	gene					1423:1426	a novel gene	1415:1426	a novel gene in fungi that potentially aids AGF to degrade pectin	1415:1479	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	11	134	theme	remarkable	2111:2120	arg1	concurrence					2122:2132	remarkable concurrence	2111:2132	remarkable concurrence of the divergence times of the rumen fungi	2111:2175	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	0	135	theme	Rumen	47:51	arg1	Fungi					53:57	Anaerobic Rumen Fungi	37:57	Anaerobic Rumen Fungi	37:57	Molecular Dating of the Emergence of Anaerobic Rumen Fungi and the Impact of Laterally Acquired Genes.
31455637	2	136	theme	Comparative	290:300	arg1	analyses					327:334	Comparative genomic and phylogenomic analyses	290:334	Comparative genomic and phylogenomic analyses of the AGF	290:345	Comparative genomic and phylogenomic analyses of the AGF have long been hampered by their fastidious growth condition, as well as their large (up to 200 Mb) and AT-biased (78 to 84%) genomes.
31455637	1	137	theme	plant	277:281	arg1	fiber					283:287	plant fiber	277:287	plant fiber	277:287	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	15	138	theme	breakdown	2865:2873	arg1	abilities					2875:2883	potential pectin breakdown abilities	2848:2883	potential pectin breakdown abilities	2848:2883	The third one is a plant-like polysaccharide lyase, representing a unique fungal enzyme with potential pectin breakdown abilities.
31455637	11	139	theme	ancestral	2223:2231	arg1	mammals					2233:2239	ancestral mammals	2223:2239	ancestral mammals	2223:2239	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	3	140	theme	genome	556:561	arg1	sequences					563:571	5 available AGF genome sequences	540:571	5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution	540:712	We sequenced 21 AGF transcriptomes and combined them with 5 available AGF genome sequences to explore their evolutionary relationships, time their divergence, and characterize gene gain/loss patterns associated with their evolution.
31455637	11	141	dep	grasses	2189:2195	arg1	forage					2182:2187	forage	2182:2187	forage	2182:2187	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	11	142	theme	fungi	2171:2175	arg1	times					2152:2156	the divergence times	2137:2156	the divergence times of the rumen fungi	2137:2175	Phylogenomics and molecular dating analyses found remarkable concurrence of the divergence times of the rumen fungi, the forage grasses, and the dietary shift of ancestral mammals from primarily insectivory to herbivory.
31455637	7	143	theme	plant-like	1371:1380	arg1	lyase					1397:1401	plant-like polysaccharide lyase	1371:1401	plant-like polysaccharide lyase	1371:1401	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	7	143	theme	plant-like	1371:1380	arg1	domain					1363:1368	A third AGF domain	1351:1368	A third AGF domain	1351:1368	A third AGF domain, plant-like polysaccharide lyase, represents a novel gene in fungi that potentially aids AGF to degrade pectin.
31455637	10	144	theme	anaerobic	1998:2006	arg1	fungi					2012:2016	these poorly characterized anaerobic gut fungi	1971:2016	these poorly characterized anaerobic gut fungi	1971:2016	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	1	145	theme	herbivorous	202:212	arg1	mammals					214:220	herbivorous mammals	202:220	herbivorous mammals	202:220	The anaerobic gut fungi (AGF), or Neocallimastigomycota, inhabit the rumen and alimentary tract of herbivorous mammals, where they play important roles in the degradation of plant fiber.
31455637	10	146	theme	characterized	1984:1996	arg1	fungi					2012:2016	these poorly characterized anaerobic gut fungi	1971:2016	these poorly characterized anaerobic gut fungi	1971:2016	We examined the origin and genomic composition of these poorly characterized anaerobic gut fungi using both transcriptome and genomic data.
31455637	5	147	theme	energy	1117:1122	arg1	acquisition					1124:1134	energy acquisition	1117:1134	energy acquisition	1117:1134	The concordance of independent estimations suggests that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials.
31637018	7	0	theme	HSPB1	1310:1314	arg1	phosphorylation					1291:1305	phosphorylation	1291:1305	phosphorylation	1291:1305	In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.
31637018	7	0	theme	HSPB1	1310:1314	arg1	O-GlcNAcylation					1271:1285	O-GlcNAcylation	1271:1285	O-GlcNAcylation	1271:1285	In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.
31637018	3	1	theme	normal	744:749	arg1	tissues					757:763	paired normal liver tissues	737:763	paired normal liver tissues	737:763	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	2	2	from	hepatoblastoma	464:477	arg1	patterns					397:404	the patterns	393:404	the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children,	393:569	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	1	3	theme	posttranslational	192:208	arg1	phosphorylation					163:177	phosphorylation	163:177	phosphorylation	163:177	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	3	theme	posttranslational	192:208	arg1	glycosylation					127:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation	85:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation)	85:157	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	3	theme	posttranslational	192:208	arg1	modifications					210:222	critical posttranslational modifications	183:222	critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors	183:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	8	4	theme	HB	1435:1436	arg1	lines					1443:1447	HB cell lines	1435:1447	HB cell lines	1435:1447	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	0	5	from	profiling	7:15	arg1	hepatoblastoma					69:82	hepatoblastoma	69:82	hepatoblastoma	69:82	Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma.
31637018	6	6	theme	cellular	1033:1040	arg1	remodeling					1073:1082	chromatin remodeling	1063:1082	chromatin remodeling	1063:1082	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	6	theme	cellular	1033:1040	arg1	transportation					1113:1126	transportation	1113:1126	transportation	1113:1126	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	6	theme	cellular	1033:1040	arg1	processes					1042:1050	multiple molecular and cellular processes	1010:1050	multiple molecular and cellular processes	1010:1050	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	6	theme	cellular	1033:1040	arg1	transcription					1085:1097	transcription	1085:1097	transcription	1085:1097	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	6	theme	cellular	1033:1040	arg1	translation					1100:1110	translation	1100:1110	translation	1100:1110	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	6	theme	cellular	1033:1040	arg1	organization					1143:1154	organelle organization	1133:1154	organelle organization	1133:1154	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	8	7	mod	modification	1342:1353	arg3	O-GlcNAcylation					1326:1340	O-GlcNAcylation modification	1326:1353	O-GlcNAcylation modification of HSPB1	1326:1362	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	8	7	mod	modification	1342:1353	arg1	HSPB1					1358:1362	HSPB1	1358:1362	HSPB1	1358:1362	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	2	8	with	tumor	520:524	arg1	incidence					548:556	an extremely low incidence	531:556	an extremely low incidence in children	531:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	6	9	theme	chromatin	1063:1071	arg1	remodeling					1073:1082	chromatin remodeling	1063:1082	chromatin remodeling	1063:1082	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	2	10	theme	detailed	364:371	arg1	characterization					373:388	a detailed characterization	362:388	a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children,	362:569	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	3	11	theme	tissues	725:731	arg1	analysis					710:717	quantitative proteomic analysis	687:717	quantitative proteomic analysis of HB tissues and paired normal liver tissues	687:763	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	2	12	from	patterns	397:404	arg1	HB					480:481	HB	480:481	HB	480:481	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	12	from	patterns	397:404	arg1	hepatoblastoma					464:477	hepatoblastoma	464:477	hepatoblastoma (HB)	464:482	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	12	from	patterns	397:404	arg1	tumor					520:524	a highly malignant primary hepatic tumor	485:524	a highly malignant primary hepatic tumor with an extremely low incidence in children	485:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	12	from	patterns	397:404	arg1	level					455:459	the peptide or protein level	432:459	level	455:459	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	9	13	theme	crucial	1562:1568	arg1	role					1570:1573	a crucial role	1560:1573	a crucial role	1560:1573	Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.
31637018	8	14	theme	chemotherapeutic	1404:1419	arg1	resistance					1421:1430	the chemotherapeutic resistance	1400:1430	the chemotherapeutic resistance of HB cell lines	1400:1447	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	1	15	theme	O-linked-β-N-acetylglucosamine	85:114	arg1	O-GlcNAcylation					142:156	O-GlcNAcylation	142:156	O-GlcNAcylation	142:156	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	15	theme	O-linked-β-N-acetylglucosamine	85:114	arg1	phosphorylation					163:177	phosphorylation	163:177	phosphorylation	163:177	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	15	theme	O-linked-β-N-acetylglucosamine	85:114	arg1	glycosylation					127:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation	85:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation)	85:157	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	15	theme	O-linked-β-N-acetylglucosamine	85:114	arg1	modifications					210:222	critical posttranslational modifications	183:222	critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors	183:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	8	16	theme	HSPB1	1358:1362	arg1	modification					1342:1353	O-GlcNAcylation modification	1326:1353	O-GlcNAcylation modification of HSPB1	1326:1362	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	2	17	theme	protein	447:453	arg1	level					455:459	the peptide or protein level	432:459	level	455:459	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	18	theme	low	544:546	arg1	incidence					548:556	an extremely low incidence	531:556	an extremely low incidence in children	531:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	3	19	theme	liver	751:755	arg1	tissues					757:763	paired normal liver tissues	737:763	paired normal liver tissues	737:763	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	0	20	theme	phosphorylated	42:55	arg1	proteins					57:64	O-GlcNAcylated and/or phosphorylated proteins	20:64	O-GlcNAcylated and/or phosphorylated proteins	20:64	Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma.
31637018	5	21	mod	modified	925:932	arg3	O-GlcNAcylation					942:956	O-GlcNAcylation	942:956	O-GlcNAcylation	942:956	Interestingly, 41 proteins were modified by both O-GlcNAcylation and phosphorylation.
31637018	5	21	mod	modified	925:932	arg3	phosphorylation					962:976	phosphorylation	962:976	phosphorylation	962:976	Interestingly, 41 proteins were modified by both O-GlcNAcylation and phosphorylation.
31637018	5	21	mod	modified	925:932	arg1	proteins					911:918	41 proteins	908:918	41 proteins	908:918	Interestingly, 41 proteins were modified by both O-GlcNAcylation and phosphorylation.
31637018	3	22	theme	tissues	757:763	arg1	analysis					710:717	quantitative proteomic analysis	687:717	quantitative proteomic analysis of HB tissues and paired normal liver tissues	687:763	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	1	23	theme	O-GlcNAc	117:124	arg1	O-GlcNAcylation					142:156	O-GlcNAcylation	142:156	O-GlcNAcylation	142:156	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	23	theme	O-GlcNAc	117:124	arg1	phosphorylation					163:177	phosphorylation	163:177	phosphorylation	163:177	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	23	theme	O-GlcNAc	117:124	arg1	glycosylation					127:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation	85:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation)	85:157	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	23	theme	O-GlcNAc	117:124	arg1	modifications					210:222	critical posttranslational modifications	183:222	critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors	183:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	2	24	theme	peptide	436:442	arg1	level					455:459	the peptide or protein level	432:459	level	455:459	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	0	25	theme	Global	0:5	arg1	profiling					7:15	Global profiling	0:15	Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma	0:82	Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma.
31637018	1	26	theme	various	331:337	arg1	tumors					345:350	various solid tumors	331:350	various solid tumors	331:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	7	27	theme	proteomics	1202:1211	arg1	results					1213:1219	the proteomics results	1198:1219	the proteomics results	1198:1219	In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.
31637018	0	28	theme	O-GlcNAcylated	20:33	arg1	proteins					57:64	O-GlcNAcylated and/or phosphorylated proteins	20:64	O-GlcNAcylated and/or phosphorylated proteins	20:64	Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma.
31637018	1	29	theme	solid	339:343	arg1	tumors					345:350	various solid tumors	331:350	various solid tumors	331:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	4	30	theme	phosphorylated	851:864	arg1	peptides					866:873	3494 phosphorylated peptides	846:873	3494 phosphorylated peptides	846:873	Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins.
31637018	2	31	from	modifications	415:427	arg1	HB					480:481	HB	480:481	HB	480:481	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	31	from	modifications	415:427	arg1	hepatoblastoma					464:477	hepatoblastoma	464:477	hepatoblastoma (HB)	464:482	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	31	from	modifications	415:427	arg1	tumor					520:524	a highly malignant primary hepatic tumor	485:524	a highly malignant primary hepatic tumor with an extremely low incidence in children	485:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	4	32	theme	O-GlcNAcylated	793:806	arg1	peptides					808:815	114 O-GlcNAcylated peptides	789:815	114 O-GlcNAcylated peptides belonging to 78 proteins	789:840	Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins.
31637018	6	33	theme	organelle	1133:1141	arg1	organization					1143:1154	organelle organization	1133:1154	organelle organization	1133:1154	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	7	34	theme	inhibitory	1245:1254	arg1	effect					1256:1261	a competitive inhibitory effect	1231:1261	a competitive inhibitory effect	1231:1261	In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.
31637018	1	35	theme	tumors	345:350	arg1	development					316:326	the development	312:326	the development of various solid tumors	312:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	35	theme	tumors	345:350	arg1	functions					260:268	the functions	256:268	the functions of proteins involved in tumorigenesis	256:306	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	8	36	theme	lines	1443:1447	arg1	resistance					1421:1430	the chemotherapeutic resistance	1400:1430	the chemotherapeutic resistance of HB cell lines	1400:1447	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	9	37	theme	HB	1598:1599	arg1	pathogenesis					1582:1593	the pathogenesis	1578:1593	the pathogenesis of HB	1578:1599	Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.
31637018	2	38	theme	hepatic	512:518	arg1	tumor					520:524	a highly malignant primary hepatic tumor	485:524	a highly malignant primary hepatic tumor with an extremely low incidence in children	485:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	38	theme	hepatic	512:518	arg1	hepatoblastoma					464:477	hepatoblastoma	464:477	hepatoblastoma (HB)	464:482	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	3	39	theme	quantitative	687:698	arg1	analysis					710:717	quantitative proteomic analysis	687:717	quantitative proteomic analysis of HB tissues and paired normal liver tissues	687:763	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	3	40	theme	O-GlcNAc-modified	613:629	arg1	peptides					651:658	peptides	651:658	peptides	651:658	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	2	41	theme	primary	504:510	arg1	tumor					520:524	a highly malignant primary hepatic tumor	485:524	a highly malignant primary hepatic tumor with an extremely low incidence in children	485:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	41	theme	primary	504:510	arg1	hepatoblastoma					464:477	hepatoblastoma	464:477	hepatoblastoma (HB)	464:482	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	6	42	theme	molecular	1019:1027	arg1	remodeling					1073:1082	chromatin remodeling	1063:1082	chromatin remodeling	1063:1082	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	42	theme	molecular	1019:1027	arg1	transportation					1113:1126	transportation	1113:1126	transportation	1113:1126	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	42	theme	molecular	1019:1027	arg1	processes					1042:1050	multiple molecular and cellular processes	1010:1050	multiple molecular and cellular processes	1010:1050	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	42	theme	molecular	1019:1027	arg1	transcription					1085:1097	transcription	1085:1097	transcription	1085:1097	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	42	theme	molecular	1019:1027	arg1	translation					1100:1110	translation	1100:1110	translation	1100:1110	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	42	theme	molecular	1019:1027	arg1	organization					1143:1154	organelle organization	1133:1154	organelle organization	1133:1154	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	7	43	theme	competitive	1233:1243	arg1	effect					1256:1261	a competitive inhibitory effect	1231:1261	a competitive inhibitory effect	1231:1261	In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.
31637018	2	44	theme	malignant	494:502	arg1	tumor					520:524	a highly malignant primary hepatic tumor	485:524	a highly malignant primary hepatic tumor with an extremely low incidence in children	485:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	44	theme	malignant	494:502	arg1	hepatoblastoma					464:477	hepatoblastoma	464:477	hepatoblastoma (HB)	464:482	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	6	45	theme	multiple	1010:1017	arg1	remodeling					1073:1082	chromatin remodeling	1063:1082	chromatin remodeling	1063:1082	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	45	theme	multiple	1010:1017	arg1	transportation					1113:1126	transportation	1113:1126	transportation	1113:1126	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	45	theme	multiple	1010:1017	arg1	processes					1042:1050	multiple molecular and cellular processes	1010:1050	multiple molecular and cellular processes	1010:1050	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	45	theme	multiple	1010:1017	arg1	transcription					1085:1097	transcription	1085:1097	transcription	1085:1097	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	45	theme	multiple	1010:1017	arg1	translation					1100:1110	translation	1100:1110	translation	1100:1110	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	6	45	theme	multiple	1010:1017	arg1	organization					1143:1154	organelle organization	1133:1154	organelle organization	1133:1154	These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization.
31637018	2	46	theme	patterns	397:404	arg1	characterization					373:388	a detailed characterization	362:388	a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children,	362:569	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	0	47	theme	proteins	57:64	arg1	profiling					7:15	Global profiling	0:15	Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma	0:82	Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma.
31637018	2	48	from	incidence	548:556	arg1	children					561:568	children	561:568	children	561:568	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	3	49	theme	HB	722:723	arg1	tissues					725:731	HB tissues	722:731	HB tissues	722:731	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	9	50	theme	O-GlcNAc-modified	1500:1516	arg1	proteins					1542:1549	O-GlcNAc-modified and/or phospho-modified proteins	1500:1549	O-GlcNAc-modified and/or phospho-modified proteins	1500:1549	Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.
31637018	1	51	theme	proteins	273:280	arg1	development					316:326	the development	312:326	the development of various solid tumors	312:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	51	theme	proteins	273:280	arg1	functions					260:268	the functions	256:268	the functions of proteins involved in tumorigenesis	256:306	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	3	52	theme	proteomic	700:708	arg1	analysis					710:717	quantitative proteomic analysis	687:717	quantitative proteomic analysis of HB tissues and paired normal liver tissues	687:763	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	1	53	theme	critical	183:190	arg1	phosphorylation					163:177	phosphorylation	163:177	phosphorylation	163:177	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	53	theme	critical	183:190	arg1	glycosylation					127:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation	85:139	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation)	85:157	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	1	53	theme	critical	183:190	arg1	modifications					210:222	critical posttranslational modifications	183:222	critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors	183:350	O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors.
31637018	3	54	theme	phospho-modified	634:649	arg1	peptides					651:658	peptides	651:658	peptides	651:658	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	2	55	from	level	455:459	arg1	patterns					397:404	the patterns	393:404	the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children,	393:569	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	2	55	from	level	455:459	arg1	modifications					415:427	these modifications	409:427	these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children,	409:569	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
31637018	8	56	theme	cell	1438:1441	arg1	lines					1443:1447	HB cell lines	1435:1447	HB cell lines	1435:1447	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	8	57	theme	O-GlcNAcylation	1326:1340	arg1	modification					1342:1353	O-GlcNAcylation modification	1326:1353	O-GlcNAcylation modification of HSPB1	1326:1362	Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro.
31637018	9	58	theme	phospho-modified	1525:1540	arg1	proteins					1542:1549	O-GlcNAc-modified and/or phospho-modified proteins	1500:1549	O-GlcNAc-modified and/or phospho-modified proteins	1500:1549	Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.
31637018	7	59	theme	results	1213:1219	arg1	accuracy					1186:1193	the accuracy	1182:1193	the accuracy of the proteomics results	1182:1219	In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1.
31637018	3	60	theme	paired	737:742	arg1	tissues					757:763	paired normal liver tissues	737:763	paired normal liver tissues	737:763	Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues.
31637018	2	61	theme	modifications	415:427	arg1	patterns					397:404	the patterns	393:404	the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children,	393:569	However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed.
30713537	6	0	theme	term	999:1002	arg1	infants					1004:1010	term infants	999:1010	term infants (n = 15)	999:1019	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	0	theme	term	999:1002	arg1	n					1013:1013	n = 15	1013:1018	n = 15	1013:1018	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	3	1	theme	glycosylation	476:488	arg1	type					461:464	the type	457:464	the type of IgG Fc glycosylation	457:488	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	8	2	theme	Increased	1510:1518	arg1	Fc					1577:1578	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc	1510:1578	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	11	3	with	galactosylation	2073:2087	arg1	age					2128:2130	lower gestational age	2110:2130	lower gestational age	2110:2130	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	6	4	theme	=	1057:1057	arg1	n					1055:1055	n = 41	1055:1060	n = 41	1055:1060	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	4	theme	=	1057:1057	arg1	mothers					1025:1031	mothers	1025:1031	mothers from preterm infants (n = 41)	1025:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	9	5	theme	preterm	1712:1718	arg1	infants					1720:1726	preterm infants	1712:1726	preterm infants born during second or third trimester of pregnancy	1712:1777	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	12	6	theme	preterm	2231:2237	arg1	infants					2239:2245	preterm infants	2231:2245	preterm infants	2231:2245	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	3	7	theme	Fc	473:474	arg1	glycosylation					476:488	IgG Fc glycosylation	469:488	IgG Fc glycosylation	469:488	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	7	8	theme	88.4	1287:1290	arg1	%					1291:1291	84.5 vs. 88.4%	1278:1291	%	1291:1291	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	11	9	theme	gestational	2116:2126	arg1	age					2128:2130	lower gestational age	2110:2130	lower gestational age	2110:2130	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	0	10	theme	IgG	0:2	arg1	Patterns					21:28	IgG Fc Glycosylation Patterns	0:28	IgG Fc Glycosylation Patterns of Preterm Infants	0:47	IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.
30713537	6	11	theme	preterm	1038:1044	arg1	infants					1046:1052	preterm infants	1038:1052	preterm infants	1038:1052	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	9	12	theme	second	1740:1745	arg1	trimester					1756:1764	second or third trimester	1740:1764	second or third trimester of pregnancy	1740:1777	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	4	13	theme	IgG	644:646	arg1	patterns					665:672	the IgG Fc glycosylation patterns	640:672	the IgG Fc glycosylation patterns in preterm infants of different gestational ages	640:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	2	14	gly	-sialylated	376:386	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	6	15	theme	Fc	908:909	arg1	patterns					925:932	IgG Fc glycosylation patterns	904:932	IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	904:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	7	16	theme	decreased	1237:1245	arg1	proportions					1247:1257	decreased proportions	1237:1257	decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1237:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	6	17	theme	mothers	1025:1031	arg1	plasma					937:942	plasma	937:942	plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	937:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	9	18	theme	third	1750:1754	arg1	trimester					1756:1764	second or third trimester	1740:1764	second or third trimester of pregnancy	1740:1777	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	2	19	theme	IgG	285:287	arg1	antibodies					289:298	IgG antibodies	285:298	IgG antibodies	285:298	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	5	20	theme	infants	809:815	arg1	samples					790:796	plasma samples	783:796	plasma samples of preterm infants (n = 38)	783:824	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	7	21	theme	gestation	1457:1465	arg1	weeks					1448:1452	≥28 weeks	1444:1452	≥28 weeks of gestation (during third trimester)	1444:1490	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	9	22	from	differences	1804:1814	arg1	patterns					1840:1847	IgG Fc glycosylation patterns	1819:1847	IgG Fc glycosylation patterns	1819:1847	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	4	23	theme	study	619:623	arg1	It					585:586	It	585:586	It	585:586	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	4	23	theme	study	619:623	arg1	aim					596:598	the aim	592:598	the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages	592:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	8	24	theme	IgG	1573:1575	arg1	Fc					1577:1578	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc	1510:1578	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	12	25	theme	IgG	2193:2195	arg1	patterns					2214:2221	IgG Fc glycosylation patterns	2193:2221	IgG Fc glycosylation patterns	2193:2221	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	6	26	theme	liquid	1086:1091	arg1	chromatography					1093:1106	high performance liquid chromatography	1069:1106	high performance liquid chromatography	1069:1106	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	3	27	theme	preterm	568:574	arg1	infants					576:582	preterm infants	568:582	preterm infants	568:582	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	8	28	theme	N-linked	1580:1587	arg1	glycans					1589:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	12	29	theme	diseases	2430:2437	arg1	development					2392:2402	the development	2388:2402	the development of sustained inflammatory diseases like BPD	2388:2446	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	7	30	theme	IgG	1214:1216	arg1	concentrations					1218:1231	reduced IgG concentrations	1206:1231	reduced IgG concentrations	1206:1231	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	6	31	theme	high	1069:1072	arg1	chromatography					1093:1106	high performance liquid chromatography	1069:1106	high performance liquid chromatography	1069:1106	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	4	32	theme	different	696:704	arg1	ages					718:721	different gestational ages	696:721	different gestational ages	696:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	5	33	theme	ELISA	872:876	arg1	use					865:867	use	865:867	use of ELISA	865:876	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	7	34	theme	preterm	1423:1429	arg1	infants					1431:1437	preterm infants	1423:1437	preterm infants born ≥28 weeks of gestation (during third trimester)	1423:1490	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	10	35	theme	preterm	1893:1899	arg1	infants					1901:1907	preterm infants	1893:1907	preterm infants	1893:1907	Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age.
30713537	4	36	theme	glycosylation	651:663	arg1	patterns					665:672	the IgG Fc glycosylation patterns	640:672	the IgG Fc glycosylation patterns in preterm infants of different gestational ages	640:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	3	37	from	diseases	556:563	arg1	infants					576:582	preterm infants	568:582	preterm infants	568:582	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	12	38	from	difference	2179:2188	arg1	patterns					2214:2221	IgG Fc glycosylation patterns	2193:2221	IgG Fc glycosylation patterns	2193:2221	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	6	39	theme	preterm	947:953	arg1	infants					955:961	preterm infants	947:961	preterm infants (n = 86, 23-34 weeks of gestation)	947:996	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	9	40	theme	IgG	1819:1821	arg1	patterns					1840:1847	IgG Fc glycosylation patterns	1819:1847	IgG Fc glycosylation patterns	1819:1847	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	10	41	theme	IgG	1860:1862	arg1	patterns					1881:1888	the IgG Fc glycosylation patterns	1856:1888	the IgG Fc glycosylation patterns of preterm infants	1856:1907	Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age.
30713537	3	42	from	reduction	409:417	arg1	type					461:464	the type	457:464	the type of IgG Fc glycosylation	457:488	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	7	43	theme	glycans	1400:1406	arg1	concentrations					1218:1231	reduced IgG concentrations	1206:1231	reduced IgG concentrations	1206:1231	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	43	theme	glycans	1400:1406	arg1	proportions					1247:1257	decreased proportions	1237:1257	decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1237:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	9	44	theme	glycosylation	1826:1838	arg1	patterns					1840:1847	IgG Fc glycosylation patterns	1819:1847	IgG Fc glycosylation patterns	1819:1847	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	8	45	theme	chronic	1637:1643	arg1	BPD					1686:1688	BPD	1686:1688	BPD	1686:1688	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	8	45	theme	chronic	1637:1643	arg1	dysplasia					1675:1683	chronic inflammatory bronchopulmonary dysplasia	1637:1683	chronic inflammatory bronchopulmonary dysplasia (BPD)	1637:1689	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	7	46	theme	Fc	1388:1389	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	46	theme	Fc	1388:1389	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	11	47	theme	IgG	2066:2068	arg1	galactosylation					2073:2087	the decreased IgG Fc galactosylation	2052:2087	the decreased IgG Fc galactosylation	2052:2087	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	11	48	theme	lower	2110:2114	arg1	age					2128:2130	lower gestational age	2110:2130	lower gestational age	2110:2130	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	6	49	from	infants	1046:1052	arg1	plasma					937:942	plasma	937:942	plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	937:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	49	from	infants	1046:1052	arg1	n					1055:1055	n = 41	1055:1060	n = 41	1055:1060	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	49	from	infants	1046:1052	arg1	infants					1004:1010	term infants	999:1010	term infants (n = 15)	999:1019	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	49	from	infants	1046:1052	arg1	infants					955:961	preterm infants	947:961	preterm infants (n = 86, 23-34 weeks of gestation)	947:996	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	49	from	infants	1046:1052	arg1	mothers					1025:1031	mothers	1025:1031	mothers from preterm infants (n = 41)	1025:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	49	from	infants	1046:1052	arg1	n					1013:1013	n = 15	1013:1018	n = 15	1013:1018	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	2	50	theme	antibodies	392:401	arg1	amount					324:329	a lower amount	316:329	a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	316:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	2	50	theme	antibodies	392:401	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	8	51	theme	bronchopulmonary	1658:1673	arg1	BPD					1686:1688	BPD	1686:1688	BPD	1686:1688	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	8	51	theme	bronchopulmonary	1658:1673	arg1	dysplasia					1675:1683	chronic inflammatory bronchopulmonary dysplasia	1637:1683	chronic inflammatory bronchopulmonary dysplasia (BPD)	1637:1689	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	12	52	from	infants	2340:2346	arg1	enrichment					2299:2308	a selective enrichment	2287:2308	a selective enrichment	2287:2308	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	7	53	theme	term	1496:1499	arg1	infants					1501:1507	term infants	1496:1507	term infants	1496:1507	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	6	54	theme	gestation	987:995	arg1	weeks					978:982	23-34 weeks	972:982	23-34 weeks of gestation	972:995	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	1	55	theme	G	136:136	arg1	IgG					139:141	IgG	139:141	IgG	139:141	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	1	55	theme	G	136:136	arg1	amounts					110:116	reduced amounts	102:116	reduced amounts of Immunoglobulin G (IgG)	102:142	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	1	55	theme	G	136:136	arg1	G					136:136	Immunoglobulin G	121:136	Immunoglobulin G (IgG)	121:142	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	12	56	theme	sustained	2407:2415	arg1	diseases					2430:2437	sustained inflammatory diseases	2407:2437	sustained inflammatory diseases like BPD	2407:2446	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	4	57	theme	ages	718:721	arg1	infants					685:691	preterm infants	677:691	preterm infants of different gestational ages	677:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	2	58	theme	-sialylated	376:386	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	5	59	theme	plasma	783:788	arg1	samples					790:796	plasma samples	783:796	plasma samples of preterm infants (n = 38)	783:824	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	7	60	theme	second	1184:1189	arg1	trimester					1191:1199	second trimester	1184:1199	second trimester	1184:1199	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	11	61	theme	N-acetylglucosamine	1969:1987	arg1	lack					1951:1954	lack	1951:1954	lack of bisecting N-acetylglucosamine	1951:1987	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	12	62	theme	selective	2289:2297	arg1	enrichment					2299:2308	a selective enrichment	2287:2308	a selective enrichment	2287:2308	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	8	63	dep	non-galactosylated	1520:1537	arg1	%					1570:1570	agalactosylated, 16.9 vs. 10.6%	1540:1570	%	1570:1570	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	0	64	theme	Glycosylation	7:19	arg1	Patterns					21:28	IgG Fc Glycosylation Patterns	0:28	IgG Fc Glycosylation Patterns of Preterm Infants	0:47	IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.
30713537	1	65	theme	reduced	102:108	arg1	IgG					139:141	IgG	139:141	IgG	139:141	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	1	65	theme	reduced	102:108	arg1	amounts					110:116	reduced amounts	102:116	reduced amounts of Immunoglobulin G (IgG)	102:142	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	1	65	theme	reduced	102:108	arg1	G					136:136	Immunoglobulin G	121:136	Immunoglobulin G (IgG)	121:142	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	7	66	theme	third	1475:1479	arg1	trimester					1481:1489	third trimester	1475:1489	third trimester	1475:1489	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	67	theme	gestation	1167:1175	arg1	weeks					1158:1162	born < 28 weeks	1148:1162	born < 28 weeks of gestation during second trimester	1148:1199	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	11	68	theme	inflammatory	2019:2030	arg1	functions					2041:2049	less inflammatory effector functions	2014:2049	less inflammatory effector functions	2014:2049	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	5	69	theme	=	820:820	arg1	n					818:818	n = 38	818:823	n = 38	818:823	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	5	69	theme	=	820:820	arg1	infants					809:815	preterm infants	801:815	preterm infants (n = 38)	801:824	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	7	70	dep	sialylated	1295:1304	arg1	%					1320:1320	14.5 vs. 17.9%	1307:1320	%	1320:1320	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	10	71	gly	glycosylation	1867:1879	arg1	infants					1901:1907	preterm infants	1893:1907	preterm infants	1893:1907	Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age.
30713537	6	72	theme	=	966:966	arg1	n					964:964	n = 86	964:969	n = 86	964:969	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	12	73	theme	preterm	2262:2268	arg1	infants					2270:2276	preterm infants	2262:2276	preterm infants	2262:2276	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	0	74	theme	Infants	41:47	arg1	Patterns					21:28	IgG Fc Glycosylation Patterns	0:28	IgG Fc Glycosylation Patterns of Preterm Infants	0:47	IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.
30713537	11	75	with	sialylation	2093:2103	arg1	age					2128:2130	lower gestational age	2110:2130	lower gestational age	2110:2130	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	7	76	theme	<	1153:1153	arg1	weeks					1158:1162	born < 28 weeks	1148:1162	born < 28 weeks of gestation during second trimester	1148:1199	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	4	77	theme	preterm	763:769	arg1	infants					771:777	preterm infants	763:777	preterm infants	763:777	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	7	78	theme	bisecting	1327:1335	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	78	theme	bisecting	1327:1335	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	10	79	theme	glycosylation	1867:1879	arg1	patterns					1881:1888	the IgG Fc glycosylation patterns	1856:1888	the IgG Fc glycosylation patterns of preterm infants	1856:1907	Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age.
30713537	2	80	theme	N-galactosylated	355:370	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	6	81	theme	infants	1004:1010	arg1	plasma					937:942	plasma	937:942	plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	937:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	2	82	theme	anti-inflammatory	334:350	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	4	83	from	patterns	665:672	arg1	infants					685:691	preterm infants	677:691	preterm infants of different gestational ages	677:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	7	84	theme	17.9	1316:1319	arg1	%					1320:1320	14.5 vs. 17.9%	1307:1320	%	1320:1320	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	85	theme	low	1119:1121	arg1	infants					1139:1145	Extremely low gestational age infants	1109:1145	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester)	1109:1200	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	10	86	theme	infants	1901:1907	arg1	patterns					1881:1888	the IgG Fc glycosylation patterns	1856:1888	the IgG Fc glycosylation patterns of preterm infants	1856:1907	Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age.
30713537	12	87	theme	glycosylation	2200:2212	arg1	patterns					2214:2221	IgG Fc glycosylation patterns	2193:2221	IgG Fc glycosylation patterns	2193:2221	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	3	88	theme	increased	514:522	arg1	risk					524:527	the increased risk	510:527	the increased risk for sustained inflammatory diseases in preterm infants	510:582	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	7	89	theme	84.5	1278:1281	arg1	%					1291:1291	84.5 vs. 88.4%	1278:1291	%	1291:1291	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	90	theme	14.5	1307:1310	arg1	%					1320:1320	14.5 vs. 17.9%	1307:1320	%	1320:1320	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	9	91	theme	infants	1720:1726	arg1	mothers					1701:1707	mothers	1701:1707	mothers of preterm infants born during second or third trimester of pregnancy	1701:1777	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	2	92	theme	reduced	267:273	arg1	amount					275:280	The reduced amount	263:280	The reduced amount of IgG antibodies	263:298	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	2	92	theme	reduced	267:273	arg1	antibodies					289:298	IgG antibodies	285:298	IgG antibodies	285:298	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	8	93	theme	non-galactosylated	1520:1537	arg1	Fc					1577:1578	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc	1510:1578	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	1	94	theme	trans-placental	148:162	arg1	transfer					164:171	trans-placental transfer	148:171	trans-placental transfer	148:171	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	7	95	theme	sialylated	1295:1304	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	95	theme	sialylated	1295:1304	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	11	96	theme	bisecting	1959:1967	arg1	N-acetylglucosamine					1969:1987	bisecting N-acetylglucosamine	1959:1987	bisecting N-acetylglucosamine	1959:1987	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	10	97	theme	gestational	1925:1935	arg1	age					1937:1939	their gestational age	1919:1939	their gestational age	1919:1939	Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age.
30713537	3	98	theme	inflammatory	543:554	arg1	diseases					556:563	sustained inflammatory diseases	533:563	sustained inflammatory diseases in preterm infants	533:582	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	8	99	theme	agalactosylated	1540:1554	arg1	%					1570:1570	agalactosylated, 16.9 vs. 10.6%	1540:1570	%	1570:1570	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	6	100	theme	glycosylation	911:923	arg1	patterns					925:932	IgG Fc glycosylation patterns	904:932	IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	904:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	12	101	theme	forms	2323:2327	arg1	enrichment					2299:2308	a selective enrichment	2287:2308	a selective enrichment	2287:2308	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	2	102	theme	antibodies	289:298	arg1	amount					275:280	The reduced amount	263:280	The reduced amount of IgG antibodies	263:298	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	2	102	theme	antibodies	289:298	arg1	antibodies					289:298	IgG antibodies	285:298	IgG antibodies	285:298	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	5	103	theme	preterm	801:807	arg1	n					818:818	n = 38	818:823	n = 38	818:823	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	5	103	theme	preterm	801:807	arg1	infants					809:815	preterm infants	801:815	preterm infants (n = 38)	801:824	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	6	104	theme	IgG	904:906	arg1	patterns					925:932	IgG Fc glycosylation patterns	904:932	IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	904:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	12	105	theme	preterm	2332:2338	arg1	infants					2340:2346	preterm infants	2332:2346	preterm infants	2332:2346	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	2	106	theme	lower	318:322	arg1	amount					324:329	a lower amount	316:329	a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	316:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	2	106	theme	lower	318:322	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	12	107	from	enrichment	2299:2308	arg1	infants					2340:2346	preterm infants	2332:2346	preterm infants	2332:2346	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	8	108	theme	10.6	1566:1569	arg1	%					1570:1570	agalactosylated, 16.9 vs. 10.6%	1540:1570	%	1570:1570	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	12	109	theme	Fc	2197:2198	arg1	patterns					2214:2221	IgG Fc glycosylation patterns	2193:2221	IgG Fc glycosylation patterns	2193:2221	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	9	110	theme	pregnancy	1769:1777	arg1	trimester					1756:1764	second or third trimester	1740:1764	second or third trimester of pregnancy	1740:1777	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	4	111	theme	explorative	607:617	arg1	study					619:623	our explorative study	603:623	our explorative study	603:623	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	6	112	theme	performance	1074:1084	arg1	chromatography					1093:1106	high performance liquid chromatography	1069:1106	high performance liquid chromatography	1069:1106	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	4	113	theme	preterm	677:683	arg1	infants					685:691	preterm infants	677:691	preterm infants of different gestational ages	677:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	8	114	theme	Fc	1577:1578	arg1	glycans					1589:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	1	115	theme	Immunoglobulin	121:134	arg1	IgG					139:141	IgG	139:141	IgG	139:141	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	1	115	theme	Immunoglobulin	121:134	arg1	G					136:136	Immunoglobulin G	121:136	Immunoglobulin G (IgG)	121:142	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	7	116	theme	galactosylated	1262:1275	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	116	theme	galactosylated	1262:1275	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	9	117	theme	significant	1792:1802	arg1	differences					1804:1814	significant differences	1792:1814	significant differences in IgG Fc glycosylation patterns	1792:1847	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	12	118	theme	glyco	2317:2321	arg1	forms					2323:2327	IgG glyco forms	2313:2327	IgG glyco forms in preterm infants	2313:2346	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	0	119	theme	Gestational	61:71	arg1	Age					73:75	Gestational Age	61:75	Gestational Age	61:75	IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.
30713537	7	120	dep	galactosylated	1262:1275	arg1	%					1291:1291	84.5 vs. 88.4%	1278:1291	%	1291:1291	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	6	121	theme	infants	955:961	arg1	plasma					937:942	plasma	937:942	plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	937:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	11	122	theme	decreased	2056:2064	arg1	galactosylation					2073:2087	the decreased IgG Fc galactosylation	2052:2087	the decreased IgG Fc galactosylation	2052:2087	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	7	123	theme	reduced	1206:1212	arg1	concentrations					1218:1231	reduced IgG concentrations	1206:1231	reduced IgG concentrations	1206:1231	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	4	124	theme	Fc	648:649	arg1	patterns					665:672	the IgG Fc glycosylation patterns	640:672	the IgG Fc glycosylation patterns in preterm infants of different gestational ages	640:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	5	125	theme	IgG	843:845	arg1	concentrations					847:860	IgG concentrations	843:860	IgG concentrations	843:860	In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA.
30713537	7	126	theme	N-linked	1391:1398	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	126	theme	N-linked	1391:1398	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	9	127	theme	Fc	1823:1824	arg1	patterns					1840:1847	IgG Fc glycosylation patterns	1819:1847	IgG Fc glycosylation patterns	1819:1847	However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns.
30713537	7	128	dep	infants	1139:1145	arg1	weeks					1158:1162	born < 28 weeks	1148:1162	born < 28 weeks of gestation during second trimester	1148:1199	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	3	129	theme	sustained	533:541	arg1	diseases					556:563	sustained inflammatory diseases	533:563	sustained inflammatory diseases in preterm infants	533:582	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	7	130	theme	IgG	1384:1386	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	130	theme	IgG	1384:1386	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	6	131	dep	infants	955:961	arg1	n					964:964	n = 86	964:969	n = 86	964:969	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	7	132	link	N-linked	1391:1398	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	132	link	N-linked	1391:1398	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	4	133	theme	term	735:738	arg1	infants					740:746	term infants	735:746	term infants	735:746	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	1	134	theme	term	188:191	arg1	infants					193:199	term infants	188:199	term infants which might explain their high susceptibility for infections	188:260	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	11	135	theme	pro-inflammatory	2149:2164	arg1	pattern					2166:2172	a rather pro-inflammatory pattern	2140:2172	a rather pro-inflammatory pattern	2140:2172	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	11	136	theme	Fc	2070:2071	arg1	galactosylation					2073:2087	the decreased IgG Fc galactosylation	2052:2087	the decreased IgG Fc galactosylation	2052:2087	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	6	137	dep	n	964:964	arg1	weeks					978:982	23-34 weeks	972:982	23-34 weeks of gestation	972:995	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	138	from	patterns	925:932	arg1	plasma					937:942	plasma	937:942	plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41)	937:1061	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	12	139	theme	inflammatory	2417:2428	arg1	diseases					2430:2437	sustained inflammatory diseases	2407:2437	sustained inflammatory diseases like BPD	2407:2446	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	2	140	theme	IgG	388:390	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	0	141	theme	Fc	4:5	arg1	Patterns					21:28	IgG Fc Glycosylation Patterns	0:28	IgG Fc Glycosylation Patterns of Preterm Infants	0:47	IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.
30713537	8	142	theme	inflammatory	1645:1656	arg1	BPD					1686:1688	BPD	1686:1688	BPD	1686:1688	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	8	142	theme	inflammatory	1645:1656	arg1	dysplasia					1675:1683	chronic inflammatory bronchopulmonary dysplasia	1637:1683	chronic inflammatory bronchopulmonary dysplasia (BPD)	1637:1689	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	1	143	theme	Preterm	78:84	arg1	infants					86:92	Preterm infants	78:92	Preterm infants	78:92	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30713537	7	144	gly	sialylated	1295:1304	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	144	gly	sialylated	1295:1304	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	6	145	from	plasma	937:942	arg1	infants					1046:1052	preterm infants	1038:1052	preterm infants	1038:1052	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	4	146	theme	gestational	706:716	arg1	ages					718:721	different gestational ages	696:721	different gestational ages	696:721	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	8	147	theme	dysplasia	1675:1683	arg1	development					1622:1632	the development	1618:1632	the development of chronic inflammatory bronchopulmonary dysplasia (BPD)	1618:1689	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	12	148	from	forms	2323:2327	arg1	infants					2340:2346	preterm infants	2332:2346	preterm infants	2332:2346	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	12	149	theme	IgG	2313:2315	arg1	forms					2323:2327	IgG glyco forms	2313:2327	IgG glyco forms in preterm infants	2313:2346	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	0	150	theme	Preterm	33:39	arg1	Infants					41:47	Preterm Infants	33:47	Preterm Infants	33:47	IgG Fc Glycosylation Patterns of Preterm Infants Differ With Gestational Age.
30713537	12	151	theme	development	2392:2402	arg1	result					2378:2383	or result	2375:2383	result	2378:2383	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	11	152	theme	effector	2032:2039	arg1	functions					2041:2049	less inflammatory effector functions	2014:2049	less inflammatory effector functions	2014:2049	Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern.
30713537	12	153	theme	infants	2270:2276	arg1	mothers					2251:2257	mothers	2251:2257	mothers	2251:2257	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	12	153	theme	infants	2270:2276	arg1	infants					2239:2245	preterm infants	2231:2245	preterm infants	2231:2245	The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.
30713537	3	154	theme	qualitative	436:446	arg1	shift					448:452	a qualitative shift	434:452	a qualitative shift in the type of IgG Fc glycosylation	434:488	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	7	155	theme	born	1148:1151	arg1	weeks					1158:1162	born < 28 weeks	1148:1162	born < 28 weeks of gestation during second trimester	1148:1199	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	3	156	from	shift	448:452	arg1	type					461:464	the type	457:464	the type of IgG Fc glycosylation	457:488	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	3	157	theme	IgG	469:471	arg1	glycosylation					476:488	IgG Fc glycosylation	469:488	IgG Fc glycosylation	469:488	This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants.
30713537	6	158	theme	=	1015:1015	arg1	infants					1004:1010	term infants	999:1010	term infants (n = 15)	999:1019	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	6	158	theme	=	1015:1015	arg1	n					1013:1013	n = 15	1013:1018	n = 15	1013:1018	Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography.
30713537	7	159	theme	age	1135:1137	arg1	infants					1139:1145	Extremely low gestational age infants	1109:1145	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester)	1109:1200	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	160	contain	had	1202:1204	arg2	proportions					1247:1257	decreased proportions	1237:1257	decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1237:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	160	contain	had	1202:1204	arg2	concentrations					1218:1231	reduced IgG concentrations	1206:1231	reduced IgG concentrations	1206:1231	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	160	contain	had	1202:1204	arg1	infants					1139:1145	Extremely low gestational age infants	1109:1145	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester)	1109:1200	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	8	161	link	N-linked	1580:1587	arg1	glycans					1589:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans	1510:1595	Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD).
30713537	7	162	theme	N-acetylglucosamine-containing	1337:1366	arg1	glycans					1400:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans	1262:1406	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	162	theme	N-acetylglucosamine-containing	1337:1366	arg1	%					1381:1381	8.4 vs. 10.8%	1369:1381	8.4 vs. 10.8%	1369:1381	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	7	163	theme	gestational	1123:1133	arg1	infants					1139:1145	Extremely low gestational age infants	1109:1145	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester)	1109:1200	Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ≥28 weeks of gestation (during third trimester) and term infants.
30713537	10	164	theme	Fc	1864:1865	arg1	patterns					1881:1888	the IgG Fc glycosylation patterns	1856:1888	the IgG Fc glycosylation patterns of preterm infants	1856:1907	Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age.
30713537	4	165	theme	infants	771:777	arg1	infants					740:746	term infants	735:746	term infants	735:746	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	4	165	theme	infants	771:777	arg1	mothers					752:758	mothers	752:758	mothers	752:758	It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants.
30713537	2	166	theme	Fc	352:353	arg1	antibodies					392:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies	334:401	The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies.
30713537	1	167	theme	high	227:230	arg1	susceptibility					232:245	their high susceptibility	221:245	their high susceptibility for infections	221:260	Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections.
30864180	4	0	theme	Phosphopeptide	516:529	arg1	enrichment					531:540	Phosphopeptide enrichment	516:540	Phosphopeptide enrichment	516:540	Phosphopeptide enrichment is performed using a TiO2 affinity technique.
30864180	5	1	theme	unique	671:676	arg1	phosphosites					678:689	1076 unique phosphosites	666:689	1076 unique phosphosites on 708 proteins	666:705	A total of 68 unique phosphohistidine sites are detected on 63 proteins among 1076 unique phosphosites on 708 proteins.
30864180	5	2	theme	sites	626:630	arg1	total					590:594	A total	588:594	A total of 68 unique phosphohistidine sites	588:630	A total of 68 unique phosphohistidine sites are detected on 63 proteins among 1076 unique phosphosites on 708 proteins.
30864180	1	3	theme	signal	174:179	arg1	transduction					181:192	signal transduction	174:192	signal transduction in prokaryotes	174:207	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30864180	0	4	from	Profiling	0:8	arg1	rerio					48:52	Danio rerio	42:52	Danio rerio by TiO2 Enrichment	42:71	Profiling of Histidine Phosphoproteome in Danio rerio by TiO2 Enrichment.
30864180	2	5	theme	N-linked	308:315	arg1	acids					338:342	N-linked phosphorylated amino acids	308:342	N-linked phosphorylated amino acids	308:342	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	2	6	from	studies	230:236	arg1	eukaryotes					241:250	eukaryotes	241:250	eukaryotes	241:250	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	3	7	theme	larvae	508:513	arg1	analysis					472:479	a global phosphorylation analysis	447:479	a global phosphorylation analysis of Danio rerio (zebrafish) larvae	447:513	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	2	8	theme	labile	291:296	arg1	nature					298:303	the labile nature	287:303	the labile nature of N-linked phosphorylated amino acids	287:342	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	3	9	theme	phosphorylation	456:470	arg1	analysis					472:479	a global phosphorylation analysis	447:479	a global phosphorylation analysis of Danio rerio (zebrafish) larvae	447:513	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	1	10	theme	Histidine	74:82	arg1	modification					135:146	a reversible post-translational modification	103:146	a reversible post-translational modification that is known to regulate signal transduction in prokaryotes	103:207	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30864180	1	10	theme	Histidine	74:82	arg1	phosphorylation					84:98	Histidine phosphorylation	74:98	Histidine phosphorylation	74:98	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30864180	7	11	theme	phosphohistidine	805:820	arg1	dataset					822:828	the first phosphohistidine dataset	795:828	the first phosphohistidine dataset obtained from zebrafish	795:852	This report provides the first phosphohistidine dataset obtained from zebrafish.
30864180	3	12	theme	vertebrate	398:407	arg1	phosphoproteome					409:423	the heretofore hidden vertebrate phosphoproteome	376:423	the heretofore hidden vertebrate phosphoproteome	376:423	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	5	13	located	detected	636:643	arg2	total					590:594	A total	588:594	A total of 68 unique phosphohistidine sites	588:630	A total of 68 unique phosphohistidine sites are detected on 63 proteins among 1076 unique phosphosites on 708 proteins.
30864180	5	13	located	detected	636:643	arg1	proteins					651:658	63 proteins	648:658	63 proteins	648:658	A total of 68 unique phosphohistidine sites are detected on 63 proteins among 1076 unique phosphosites on 708 proteins.
30864180	2	14	theme	acids	338:342	arg1	nature					298:303	the labile nature	287:303	the labile nature of N-linked phosphorylated amino acids	287:342	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	5	15	theme	unique	602:607	arg1	sites					626:630	68 unique phosphohistidine sites	599:630	68 unique phosphohistidine sites	599:630	A total of 68 unique phosphohistidine sites are detected on 63 proteins among 1076 unique phosphosites on 708 proteins.
30864180	2	16	theme	amino	332:336	arg1	acids					338:342	N-linked phosphorylated amino acids	308:342	N-linked phosphorylated amino acids	308:342	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	3	17	theme	global	449:454	arg1	analysis					472:479	a global phosphorylation analysis	447:479	a global phosphorylation analysis of Danio rerio (zebrafish) larvae	447:513	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	0	18	theme	Phosphoproteome	23:37	arg1	Profiling					0:8	Profiling	0:8	Profiling of Histidine Phosphoproteome in Danio rerio by TiO2 Enrichment.	0:72	Profiling of Histidine Phosphoproteome in Danio rerio by TiO2 Enrichment.
30864180	5	19	theme	phosphohistidine	609:624	arg1	sites					626:630	68 unique phosphohistidine sites	599:630	68 unique phosphohistidine sites	599:630	A total of 68 unique phosphohistidine sites are detected on 63 proteins among 1076 unique phosphosites on 708 proteins.
30864180	2	20	theme	phosphorylated	317:330	arg1	acids					338:342	N-linked phosphorylated amino acids	308:342	N-linked phosphorylated amino acids	308:342	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	3	21	theme	rerio	490:494	arg1	larvae					508:513	Danio rerio (zebrafish) larvae	484:513	Danio rerio (zebrafish) larvae	484:513	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	0	22	theme	Histidine	13:21	arg1	Phosphoproteome					23:37	Histidine Phosphoproteome	13:37	Histidine Phosphoproteome	13:37	Profiling of Histidine Phosphoproteome in Danio rerio by TiO2 Enrichment.
30864180	3	23	attach	presents	438:445	arg2	report					431:436	this report	426:436	this report	426:436	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	3	23	attach	presents	438:445	arg1	effort					351:356	an effort to help elucidate the heretofore hidden vertebrate phosphoproteome	348:423	an effort to help elucidate the heretofore hidden vertebrate phosphoproteome	348:423	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	1	24	theme	reversible	105:114	arg1	modification					135:146	a reversible post-translational modification	103:146	a reversible post-translational modification that is known to regulate signal transduction in prokaryotes	103:207	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30864180	1	24	theme	reversible	105:114	arg1	phosphorylation					84:98	Histidine phosphorylation	74:98	Histidine phosphorylation	74:98	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30864180	0	25	theme	Danio	42:46	arg1	rerio					48:52	Danio rerio	42:52	Danio rerio by TiO2 Enrichment	42:71	Profiling of Histidine Phosphoproteome in Danio rerio by TiO2 Enrichment.
30864180	5	26	from	phosphosites	678:689	arg1	proteins					698:705	708 proteins	694:705	708 proteins	694:705	A total of 68 unique phosphohistidine sites are detected on 63 proteins among 1076 unique phosphosites on 708 proteins.
30864180	3	27	theme	Danio	484:488	arg1	larvae					508:513	Danio rerio (zebrafish) larvae	484:513	Danio rerio (zebrafish) larvae	484:513	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	2	28	link	N-linked	308:315	arg1	acids					338:342	N-linked phosphorylated amino acids	308:342	N-linked phosphorylated amino acids	308:342	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	1	29	theme	post-translational	116:133	arg1	modification					135:146	a reversible post-translational modification	103:146	a reversible post-translational modification that is known to regulate signal transduction in prokaryotes	103:207	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30864180	1	29	theme	post-translational	116:133	arg1	phosphorylation					84:98	Histidine phosphorylation	74:98	Histidine phosphorylation	74:98	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30864180	6	30	with	ProteomeXchange	731:745	arg1	identifier					752:761	identifier PXD012735	752:771	identifier PXD012735	752:771	Data are available via ProteomeXchange with identifier PXD012735.
30864180	4	31	theme	affinity	568:575	arg1	technique					577:585	a TiO2 affinity technique	561:585	a TiO2 affinity technique	561:585	Phosphopeptide enrichment is performed using a TiO2 affinity technique.
30864180	4	32	theme	TiO2	563:566	arg1	technique					577:585	a TiO2 affinity technique	561:585	a TiO2 affinity technique	561:585	Phosphopeptide enrichment is performed using a TiO2 affinity technique.
30864180	2	33	theme	functional	219:228	arg1	studies					230:236	functional studies	219:236	functional studies in eukaryotes	219:250	However, functional studies in eukaryotes have been largely neglected due to the labile nature of N-linked phosphorylated amino acids.
30864180	3	34	theme	zebrafish	497:505	arg1	larvae					508:513	Danio rerio (zebrafish) larvae	484:513	Danio rerio (zebrafish) larvae	484:513	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	7	35	theme	first	799:803	arg1	dataset					822:828	the first phosphohistidine dataset	795:828	the first phosphohistidine dataset obtained from zebrafish	795:852	This report provides the first phosphohistidine dataset obtained from zebrafish.
30864180	0	36	theme	TiO2	57:60	arg1	Enrichment					62:71	TiO2 Enrichment	57:71	TiO2 Enrichment	57:71	Profiling of Histidine Phosphoproteome in Danio rerio by TiO2 Enrichment.
30864180	3	37	theme	hidden	391:396	arg1	phosphoproteome					409:423	the heretofore hidden vertebrate phosphoproteome	376:423	the heretofore hidden vertebrate phosphoproteome	376:423	In an effort to help elucidate the heretofore hidden vertebrate phosphoproteome, this report presents a global phosphorylation analysis of Danio rerio (zebrafish) larvae.
30864180	1	38	from	transduction	181:192	arg1	prokaryotes					197:207	prokaryotes	197:207	prokaryotes	197:207	Histidine phosphorylation is a reversible post-translational modification that is known to regulate signal transduction in prokaryotes.
30479582	0	0	theme	Trypsin	82:88	arg1	Digestion					90:98	Trypsin Digestion	82:98	Trypsin Digestion of Immunoglobulin Gs (IgGs)	82:126	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	4	1	gly	glycopeptides	777:789	arg2	glycopeptides					777:789	glycopeptides	777:789	glycopeptides from rabbit IgGs	777:806	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	4	1	gly	glycopeptides	777:789	arg1	IgGs					803:806	rabbit IgGs	796:806	rabbit IgGs	796:806	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	1	2	gly	glycoforms	336:345	arg1	low-abundance					322:334	low-abundance glycoforms	322:345	low-abundance glycoforms	322:345	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	4	3	theme	glycopeptides	711:723	arg1	behavior					699:706	the retention behavior	685:706	the retention behavior of glycopeptides from human IgGs	685:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	2	4	gly	glycosylation	433:445	arg1	IgG					462:464	recombinant IgG	450:464	recombinant IgG	450:464	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	1	5	gly	glycoproteins	235:247	arg1	characterization					302:317	the characterization	298:317	the characterization of low-abundance glycoforms	298:345	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	1	5	gly	glycoproteins	235:247	arg1	challenges					278:287	the analytical challenges	263:287	particularly the analytical challenges	250:287	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	1	5	gly	glycoproteins	235:247	arg1	glycoproteins					235:247	glycoproteins	235:247	glycoproteins	235:247	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	4	6	from	behavior	699:706	arg1	IgGs					736:739	human IgGs	730:739	human IgGs	730:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	1	7	theme	analytical	267:276	arg1	characterization					302:317	the characterization	298:317	the characterization of low-abundance glycoforms	298:345	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	1	7	theme	analytical	267:276	arg1	challenges					278:287	the analytical challenges	263:287	particularly the analytical challenges	250:287	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	1	7	theme	analytical	267:276	arg1	glycoproteins					235:247	glycoproteins	235:247	glycoproteins	235:247	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	2	8	from	IgG	462:464	arg1	amount					423:428	amount	423:428	amount	423:428	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	2	8	from	IgG	462:464	arg1	type					414:417	type	414:417	type	414:417	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	2	8	from	IgG	462:464	arg1	glycosylation					433:445	glycosylation	433:445	glycosylation on recombinant IgG	433:464	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	2	9	from	essential	361:369	arg1	industry					394:401	the biotherapeutics industry	374:401	the biotherapeutics industry	374:401	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	3	10	theme	hydrophilic	555:565	arg1	chromatography					586:599	hydrophilic interaction liquid chromatography	555:599	the hydrophilic interaction liquid chromatography retention of peptides and glycans	551:633	Models exist for the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans.
30479582	5	11	theme	spectrometry	959:970	arg1	systems					972:978	2 completely different liquid chromatography-mass spectrometry systems	909:978	2 completely different liquid chromatography-mass spectrometry systems	909:978	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	0	12	theme	Gs	118:119	arg1	Digestion					90:98	Trypsin Digestion	82:98	Trypsin Digestion of Immunoglobulin Gs (IgGs)	82:126	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	5	13	theme	different	922:930	arg1	systems					972:978	2 completely different liquid chromatography-mass spectrometry systems	909:978	2 completely different liquid chromatography-mass spectrometry systems	909:978	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	4	14	from	analysis	765:772	arg1	IgGs					803:806	rabbit IgGs	796:806	rabbit IgGs	796:806	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	1	15	theme	retention	151:159	arg1	behavior/time					161:173	the retention behavior/time	147:173	the retention behavior/time	147:173	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	0	16	theme	Immunoglobulin	103:116	arg1	IgGs					122:125	IgGs	122:125	IgGs	122:125	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	0	16	theme	Immunoglobulin	103:116	arg1	Gs					118:119	Immunoglobulin Gs	103:119	Immunoglobulin Gs (IgGs)	103:126	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	4	17	theme	glycopeptides	777:789	arg1	analysis					765:772	the analysis	761:772	the analysis of glycopeptides from rabbit IgGs	761:806	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	1	18	theme	behavior/time	161:173	arg1	prediction					133:142	The prediction	129:142	The prediction of the retention behavior/time	129:173	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	5	19	theme	combined	813:820	arg1	model					822:826	The combined model	809:826	The combined model	809:826	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	5	19	theme	combined	813:820	arg1	capable					831:837	capable	831:837	capable	831:837	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	3	20	theme	chromatography	586:599	arg1	retention					601:609	the hydrophilic interaction liquid chromatography retention	551:609	the hydrophilic interaction liquid chromatography retention of peptides and glycans	551:633	Models exist for the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans.
30479582	5	21	theme	native	881:886	arg1	glycopeptides					892:904	native IgG glycopeptides	881:904	native IgG glycopeptides	881:904	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	4	22	from	IgGs	803:806	arg1	glycopeptides					777:789	glycopeptides	777:789	glycopeptides from rabbit IgGs	777:806	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	4	22	from	IgGs	803:806	arg1	analysis					765:772	the analysis	761:772	the analysis of glycopeptides from rabbit IgGs	761:806	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	2	23	from	industry	394:401	arg1	essential					361:369	essential	361:369	essential	361:369	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	3	24	theme	retention	601:609	arg1	prediction					537:546	the prediction	533:546	the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans	533:633	Models exist for the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans.
30479582	5	25	theme	IgG	888:890	arg1	glycopeptides					892:904	native IgG glycopeptides	881:904	native IgG glycopeptides	881:904	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	0	26	theme	Retention	21:29	arg1	Behavior					31:38	the HILIC Retention Behavior	11:38	the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs)	11:126	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	5	27	from	retention	868:876	arg1	systems					972:978	2 completely different liquid chromatography-mass spectrometry systems	909:978	2 completely different liquid chromatography-mass spectrometry systems	909:978	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	3	28	theme	interaction	567:577	arg1	chromatography					586:599	hydrophilic interaction liquid chromatography	555:599	the hydrophilic interaction liquid chromatography retention of peptides and glycans	551:633	Models exist for the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans.
30479582	2	29	theme	glycosylation	433:445	arg1	amount					423:428	amount	423:428	amount	423:428	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	2	29	theme	glycosylation	433:445	arg1	type					414:417	type	414:417	type	414:417	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	2	29	theme	glycosylation	433:445	arg1	glycosylation					433:445	glycosylation	433:445	glycosylation on recombinant IgG	433:464	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	0	30	theme	HILIC	15:19	arg1	Behavior					31:38	the HILIC Retention Behavior	11:38	the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs)	11:126	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	3	31	theme	liquid	579:584	arg1	chromatography					586:599	hydrophilic interaction liquid chromatography	555:599	the hydrophilic interaction liquid chromatography retention of peptides and glycans	551:633	Models exist for the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans.
30479582	4	32	theme	unified	660:666	arg1	model					668:672	a unified model	658:672	a unified model to predict the retention behavior of glycopeptides from human IgGs	658:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	2	33	theme	recombinant	450:460	arg1	IgG					462:464	recombinant IgG	450:464	recombinant IgG	450:464	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	0	34	theme	N-Linked	47:54	arg1	Glycopeptides					56:68	the N-Linked Glycopeptides	43:68	the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs)	43:126	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	1	35	theme	low-abundance	322:334	arg1	glycoforms					336:345	low-abundance glycoforms	322:345	low-abundance glycoforms	322:345	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	4	36	theme	human	730:734	arg1	IgGs					736:739	human IgGs	730:739	human IgGs	730:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	1	37	theme	glycoforms	336:345	arg1	characterization					302:317	the characterization	298:317	the characterization of low-abundance glycoforms	298:345	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	5	38	gly	glycopeptides	892:904	arg2	glycopeptides					892:904	native IgG glycopeptides	881:904	native IgG glycopeptides	881:904	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	3	39	theme	peptides	614:621	arg1	retention					601:609	the hydrophilic interaction liquid chromatography retention	551:609	the hydrophilic interaction liquid chromatography retention of peptides and glycans	551:633	Models exist for the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans.
30479582	2	40	from	type	414:417	arg1	IgG					462:464	recombinant IgG	450:464	recombinant IgG	450:464	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	5	41	theme	liquid	932:937	arg1	spectrometry					959:970	liquid chromatography-mass spectrometry	932:970	2 completely different liquid chromatography-mass spectrometry systems	909:978	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	3	42	theme	glycans	627:633	arg1	retention					601:609	the hydrophilic interaction liquid chromatography retention	551:609	the hydrophilic interaction liquid chromatography retention of peptides and glycans	551:633	Models exist for the prediction of the hydrophilic interaction liquid chromatography retention of peptides and glycans.
30479582	5	43	theme	chromatography-mass	939:957	arg1	spectrometry					959:970	liquid chromatography-mass spectrometry	932:970	2 completely different liquid chromatography-mass spectrometry systems	909:978	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	4	44	from	IgGs	736:739	arg1	glycopeptides					711:723	glycopeptides	711:723	glycopeptides from human IgGs	711:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	4	44	from	IgGs	736:739	arg1	behavior					699:706	the retention behavior	685:706	the retention behavior of glycopeptides from human IgGs	685:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	4	45	gly	glycopeptides	711:723	arg1	IgGs					736:739	human IgGs	730:739	human IgGs	730:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	4	45	gly	glycopeptides	711:723	arg2	glycopeptides					711:723	glycopeptides	711:723	glycopeptides from human IgGs	711:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	4	46	theme	rabbit	796:801	arg1	IgGs					803:806	rabbit IgGs	796:806	rabbit IgGs	796:806	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	2	47	from	amount	423:428	arg1	IgG					462:464	recombinant IgG	450:464	recombinant IgG	450:464	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	4	48	theme	retention	689:697	arg1	behavior					699:706	the retention behavior	685:706	the retention behavior of glycopeptides from human IgGs	685:739	Here, we have devised a unified model to predict the retention behavior of glycopeptides from human IgGs and applied this to the analysis of glycopeptides from rabbit IgGs.
30479582	1	49	theme	glycoproteins	235:247	arg1	identification					196:209	identification	196:209	identification	196:209	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	1	49	theme	glycoproteins	235:247	arg1	characterization					215:230	characterization	215:230	characterization	215:230	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	2	50	dep	type	414:417	arg1	the					410:412	the	410:412	the	410:412	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	5	51	theme	glycopeptides	892:904	arg1	retention					868:876	the retention	864:876	the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems	864:978	The combined model is capable of accurately predicting the retention of native IgG glycopeptides on 2 completely different liquid chromatography-mass spectrometry systems.
30479582	0	52	theme	Glycopeptides	56:68	arg1	Behavior					31:38	the HILIC Retention Behavior	11:38	the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs)	11:126	Predicting the HILIC Retention Behavior of the N-Linked Glycopeptides Produced by Trypsin Digestion of Immunoglobulin Gs (IgGs).
30479582	1	53	dep	identification	196:209	arg1	the					192:194	the	192:194	the	192:194	The prediction of the retention behavior/time would facilitate the identification and characterization of glycoproteins, particularly the analytical challenges, such as the characterization of low-abundance glycoforms.
30479582	2	54	from	glycosylation	433:445	arg1	IgG					462:464	recombinant IgG	450:464	recombinant IgG	450:464	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
30479582	2	55	theme	biotherapeutics	378:392	arg1	industry					394:401	the biotherapeutics industry	374:401	the biotherapeutics industry	374:401	This task is essential in the biotherapeutics industry, where the type and amount of glycosylation on recombinant IgG alter the efficacy, function, and immunogenicity.
31077402	4	0	theme	Pgm2	719:722	arg1	model					775:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	1	1	theme	congenital	165:174	arg1	deficiency					151:160	phosphoglucomutase (PGM1) deficiency	125:160	phosphoglucomutase (PGM1) deficiency	125:160	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	1	1	theme	congenital	165:174	arg1	disorder					176:183	a congenital disorder	163:183	a congenital disorder of glycosylation (CDG)	163:206	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	9	2	theme	abnormal	1425:1432	arg1	pattern					1448:1454	an abnormal glycosylation pattern	1422:1454	an abnormal glycosylation pattern	1422:1454	However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
31077402	0	3	theme	embryonic	90:98	arg1	lethality					100:108	early embryonic lethality	84:108	early embryonic lethality	84:108	A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.
31077402	6	4	theme	pregnancy	1052:1060	arg1	course					1042:1047	the course	1038:1047	the course of pregnancy	1038:1060	Ultrasound studies of the course of pregnancy confirmed Pgm2-deficient pups succumb before E9.5.
31077402	9	5	from	analyses	1395:1402	arg1	serum					1407:1411	serum	1407:1411	serum	1407:1411	However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
31077402	5	6	theme	lethality	976:984	arg1	phenotype					986:994	an embryonic lethality phenotype	963:994	an embryonic lethality phenotype in the homozygotes	963:1013	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	7	7	theme	galactose	1118:1126	arg1	water					1162:1166	9 mg/mL drinking water	1145:1166	9 mg/mL drinking water	1145:1166	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	7	7	theme	galactose	1118:1126	arg1	supplementation					1128:1142	Oral galactose supplementation	1113:1142	Oral galactose supplementation (9 mg/mL drinking water)	1113:1167	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	9	8	theme	Pgm2+/-	1463:1469	arg1	animals					1471:1477	the Pgm2+/- animals	1459:1477	the Pgm2+/- animals	1459:1477	However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
31077402	3	9	theme	enzyme	562:567	arg1	roles					549:553	the central roles	537:553	the central roles of the enzyme in (glycogen) metabolism and glycosylation	537:610	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	10	theme	glycogen	573:580	arg1	metabolism					583:592	(glycogen) metabolism	572:592	(glycogen) metabolism	572:592	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	5	11	theme	=	936:936	arg1	pups					928:931	78 newborn pups	917:931	78 newborn pups (P = 1.59897E-06)	917:949	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	5	11	theme	=	936:936	arg1	P					934:934	P = 1.59897E-06	934:948	P = 1.59897E-06	934:948	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	4	12	theme	mouse	725:729	arg1	ortholog					731:738	mouse ortholog	725:738	mouse ortholog of human PGM1	725:752	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	9	13	theme	similar	1480:1486	arg1	pattern					1448:1454	an abnormal glycosylation pattern	1422:1454	an abnormal glycosylation pattern	1422:1454	However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
31077402	4	14	theme	human	743:747	arg1	PGM1					749:752	human PGM1	743:752	human PGM1	743:752	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	3	15	from	roles	549:553	arg1	glycosylation					598:610	glycosylation	598:610	glycosylation	598:610	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	15	from	roles	549:553	arg1	metabolism					583:592	(glycogen) metabolism	572:592	(glycogen) metabolism	572:592	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	4	16	dep	Pgm2	719:722	arg1	ortholog					731:738	mouse ortholog	725:738	mouse ortholog of human PGM1	725:752	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	8	17	theme	Biochemical	1199:1209	arg1	studies					1211:1217	Biochemical studies	1199:1217	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals	1199:1285	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	3	18	theme	lethal	459:464	arg1	hypoglycemia					356:367	severe hypoglycemia	349:367	severe hypoglycemia	349:367	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	18	theme	lethal	459:464	arg1	hepatopathy					370:380	hepatopathy	370:380	hepatopathy	370:380	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	18	theme	lethal	459:464	arg1	deficiencies					412:423	hormonal deficiencies	403:423	hormonal deficiencies	403:423	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	18	theme	lethal	459:464	arg1	early-onset					467:477	early-onset	467:477	early-onset of dilated cardiomyopathy and myopathy	467:516	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	18	theme	lethal	459:464	arg1	anomalies					437:445	hemostatic anomalies	426:445	hemostatic anomalies	426:445	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	18	theme	lethal	459:464	arg1	retardation					390:400	growth retardation	383:400	growth retardation	383:400	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	7	19	theme	drinking	1153:1160	arg1	water					1162:1166	9 mg/mL drinking water	1145:1166	9 mg/mL drinking water	1145:1166	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	7	19	theme	drinking	1153:1160	arg1	supplementation					1128:1142	Oral galactose supplementation	1113:1142	Oral galactose supplementation (9 mg/mL drinking water)	1113:1167	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	5	20	theme	multiple	817:824	arg1	crosses					826:832	multiple crosses	817:832	multiple crosses between heterozygous parents	817:861	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	8	21	from	change	1348:1353	arg1	content					1367:1373	glycogen content	1358:1373	glycogen content	1358:1373	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	2	22	attach	present	275:281	arg2	defects					263:269	Midline cleft defects	249:269	Midline cleft defects	249:269	Midline cleft defects are present at birth.
31077402	2	22	attach	present	275:281	arg1	birth					286:290	birth	286:290	birth	286:290	Midline cleft defects are present at birth.
31077402	5	23	from	phenotype	986:994	arg1	homozygotes					1003:1013	the homozygotes	999:1013	the homozygotes	999:1013	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	1	24	theme	glycosylation	188:200	arg1	deficiency					151:160	phosphoglucomutase (PGM1) deficiency	125:160	phosphoglucomutase (PGM1) deficiency	125:160	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	1	24	theme	glycosylation	188:200	arg1	disorder					176:183	a congenital disorder	163:183	a congenital disorder of glycosylation (CDG)	163:206	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	0	25	theme	novel	2:6	arg1	model					43:47	A novel phosphoglucomutase-deficient mouse model	0:47	A novel phosphoglucomutase-deficient mouse model	0:47	A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.
31077402	4	26	theme	-knockout	754:762	arg1	model					775:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	6	27	theme	Pgm2-deficient	1072:1085	arg1	pups					1087:1090	Pgm2-deficient pups	1072:1090	Pgm2-deficient pups succumb before E9.5	1072:1110	Ultrasound studies of the course of pregnancy confirmed Pgm2-deficient pups succumb before E9.5.
31077402	3	28	theme	hormonal	403:410	arg1	hypoglycemia					356:367	severe hypoglycemia	349:367	severe hypoglycemia	349:367	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	28	theme	hormonal	403:410	arg1	deficiencies					412:423	hormonal deficiencies	403:423	hormonal deficiencies	403:423	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	8	29	theme	glycogen	1358:1365	arg1	content					1367:1373	glycogen content	1358:1373	glycogen content	1358:1373	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	8	30	theme	tissues	1222:1228	arg1	studies					1211:1217	Biochemical studies	1199:1217	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals	1199:1285	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	4	31	theme	mouse	769:773	arg1	model					775:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	5	32	theme	homozygous	891:900	arg1	births					907:912	homozygous life births	891:912	homozygous life births in 78 newborn pups (P = 1.59897E-06)	891:949	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	3	33	theme	growth	383:388	arg1	retardation					390:400	growth retardation	383:400	growth retardation	383:400	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	33	theme	growth	383:388	arg1	hypoglycemia					356:367	severe hypoglycemia	349:367	severe hypoglycemia	349:367	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	9	34	from	pattern	1448:1454	arg1	animals					1471:1477	the Pgm2+/- animals	1459:1477	the Pgm2+/- animals	1459:1477	However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
31077402	5	35	from	births	907:912	arg1	pups					928:931	78 newborn pups	917:931	78 newborn pups (P = 1.59897E-06)	917:949	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	5	35	from	births	907:912	arg1	P					934:934	P = 1.59897E-06	934:948	P = 1.59897E-06	934:948	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	4	36	theme	KO	765:766	arg1	model					775:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	3	37	theme	dilated	482:488	arg1	cardiomyopathy					490:503	dilated cardiomyopathy	482:503	dilated cardiomyopathy	482:503	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	1	38	with	Patients	111:118	arg1	deficiency					151:160	phosphoglucomutase (PGM1) deficiency	125:160	phosphoglucomutase (PGM1) deficiency	125:160	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	1	38	with	Patients	111:118	arg1	disorder					176:183	a congenital disorder	163:183	a congenital disorder of glycosylation (CDG)	163:206	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	5	39	theme	embryonic	966:974	arg1	phenotype					986:994	an embryonic lethality phenotype	963:994	an embryonic lethality phenotype in the homozygotes	963:1013	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	1	40	theme	phosphoglucomutase	125:142	arg1	deficiency					151:160	phosphoglucomutase (PGM1) deficiency	125:160	phosphoglucomutase (PGM1) deficiency	125:160	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	1	40	theme	phosphoglucomutase	125:142	arg1	disorder					176:183	a congenital disorder	163:183	a congenital disorder of glycosylation (CDG)	163:206	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	3	41	theme	cardiomyopathy	490:503	arg1	hypoglycemia					356:367	severe hypoglycemia	349:367	severe hypoglycemia	349:367	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	41	theme	cardiomyopathy	490:503	arg1	early-onset					467:477	early-onset	467:477	early-onset of dilated cardiomyopathy and myopathy	467:516	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	42	theme	hemostatic	426:435	arg1	hypoglycemia					356:367	severe hypoglycemia	349:367	severe hypoglycemia	349:367	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	42	theme	hemostatic	426:435	arg1	anomalies					437:445	hemostatic anomalies	426:445	hemostatic anomalies	426:445	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	8	43	theme	enzyme	1310:1315	arg1	activity					1317:1324	reduced Pgm2 enzyme activity	1297:1324	reduced Pgm2 enzyme activity	1297:1324	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	6	44	theme	course	1042:1047	arg1	studies					1027:1033	Ultrasound studies	1016:1033	Ultrasound studies of the course of pregnancy	1016:1060	Ultrasound studies of the course of pregnancy confirmed Pgm2-deficient pups succumb before E9.5.
31077402	2	45	theme	Midline	249:255	arg1	defects					263:269	Midline cleft defects	249:269	Midline cleft defects	249:269	Midline cleft defects are present at birth.
31077402	4	46	theme	phenotypes	677:686	arg1	pathophysiology					630:644	the pathophysiology	626:644	the pathophysiology of the tissue-specific disease phenotypes	626:686	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	0	47	theme	phosphoglucomutase-deficient	8:35	arg1	model					43:47	A novel phosphoglucomutase-deficient mouse model	0:47	A novel phosphoglucomutase-deficient mouse model	0:47	A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.
31077402	9	48	theme	glycosylation	1434:1446	arg1	pattern					1448:1454	an abnormal glycosylation pattern	1422:1454	an abnormal glycosylation pattern	1422:1454	However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
31077402	8	49	theme	Pgm2	1305:1308	arg1	activity					1317:1324	reduced Pgm2 enzyme activity	1297:1324	reduced Pgm2 enzyme activity	1297:1324	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	0	50	theme	mouse	37:41	arg1	model					43:47	A novel phosphoglucomutase-deficient mouse model	0:47	A novel phosphoglucomutase-deficient mouse model	0:47	A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.
31077402	1	51	theme	multiple	220:227	arg1	phenotypes					237:246	multiple disease phenotypes	220:246	multiple disease phenotypes	220:246	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	7	52	theme	mg/mL	1147:1151	arg1	water					1162:1166	9 mg/mL drinking water	1145:1166	9 mg/mL drinking water	1145:1166	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	7	52	theme	mg/mL	1147:1151	arg1	supplementation					1128:1142	Oral galactose supplementation	1113:1142	Oral galactose supplementation (9 mg/mL drinking water)	1113:1167	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	5	53	theme	life	902:905	arg1	births					907:912	homozygous life births	891:912	homozygous life births in 78 newborn pups (P = 1.59897E-06)	891:949	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	3	54	theme	clinical	314:321	arg1	phenotypes					323:332	additional clinical phenotypes	303:332	additional clinical phenotypes	303:332	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	5	55	theme	newborn	920:926	arg1	pups					928:931	78 newborn pups	917:931	78 newborn pups (P = 1.59897E-06)	917:949	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	5	55	theme	newborn	920:926	arg1	P					934:934	P = 1.59897E-06	934:948	P = 1.59897E-06	934:948	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	0	56	theme	aberrant	57:64	arg1	glycosylation					66:78	aberrant glycosylation	57:78	aberrant glycosylation	57:78	A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.
31077402	9	57	theme	glycomics	1385:1393	arg1	analyses					1395:1402	glycomics analyses	1385:1402	glycomics analyses in serum	1385:1411	However, glycomics analyses in serum revealed an abnormal glycosylation pattern in the Pgm2+/- animals, similar to that seen in PGM1-CDG.
31077402	6	58	dep	pups	1087:1090	arg1	succumb					1092:1098	succumb	1092:1098	succumb before E9.5	1092:1110	Ultrasound studies of the course of pregnancy confirmed Pgm2-deficient pups succumb before E9.5.
31077402	7	59	theme	Oral	1113:1116	arg1	water					1162:1166	9 mg/mL drinking water	1145:1166	9 mg/mL drinking water	1145:1166	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	7	59	theme	Oral	1113:1116	arg1	supplementation					1128:1142	Oral galactose supplementation	1113:1142	Oral galactose supplementation (9 mg/mL drinking water)	1113:1167	Oral galactose supplementation (9 mg/mL drinking water) did not rescue the lethality.
31077402	1	60	theme	PGM1	145:148	arg1	deficiency					151:160	phosphoglucomutase (PGM1) deficiency	125:160	phosphoglucomutase (PGM1) deficiency	125:160	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	1	60	theme	PGM1	145:148	arg1	disorder					176:183	a congenital disorder	163:183	a congenital disorder of glycosylation (CDG)	163:206	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	2	61	from	birth	286:290	arg1	present					275:281	present	275:281	present	275:281	Midline cleft defects are present at birth.
31077402	8	62	theme	heterozygous	1266:1277	arg1	animals					1279:1285	heterozygous animals	1266:1285	heterozygous animals	1266:1285	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	4	63	theme	PGM1	749:752	arg1	ortholog					731:738	mouse ortholog	725:738	mouse ortholog of human PGM1	725:752	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	8	64	theme	reduced	1297:1303	arg1	activity					1317:1324	reduced Pgm2 enzyme activity	1297:1324	reduced Pgm2 enzyme activity	1297:1324	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	1	65	theme	disease	229:235	arg1	phenotypes					237:246	multiple disease phenotypes	220:246	multiple disease phenotypes	220:246	Patients with phosphoglucomutase (PGM1) deficiency, a congenital disorder of glycosylation (CDG) suffer from multiple disease phenotypes.
31077402	3	66	theme	additional	303:312	arg1	phenotypes					323:332	additional clinical phenotypes	303:332	additional clinical phenotypes	303:332	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	4	67	theme	CRISPR-Cas9	787:797	arg1	technology					799:808	CRISPR-Cas9 technology	787:808	CRISPR-Cas9 technology	787:808	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	3	68	theme	myopathy	509:516	arg1	hypoglycemia					356:367	severe hypoglycemia	349:367	severe hypoglycemia	349:367	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	68	theme	myopathy	509:516	arg1	early-onset					467:477	early-onset	467:477	early-onset of dilated cardiomyopathy and myopathy	467:516	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	8	69	theme	skin	1234:1237	arg1	fibroblasts					1239:1249	skin fibroblasts	1234:1249	skin fibroblasts	1234:1249	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	2	70	located	present	275:281	arg2	defects					263:269	Midline cleft defects	249:269	Midline cleft defects	249:269	Midline cleft defects are present at birth.
31077402	2	70	located	present	275:281	arg1	birth					286:290	birth	286:290	birth	286:290	Midline cleft defects are present at birth.
31077402	0	71	theme	early	84:88	arg1	lethality					100:108	early embryonic lethality	84:108	early embryonic lethality	84:108	A novel phosphoglucomutase-deficient mouse model reveals aberrant glycosylation and early embryonic lethality.
31077402	4	72	theme	disease	669:675	arg1	phenotypes					677:686	the tissue-specific disease phenotypes	649:686	the tissue-specific disease phenotypes	649:686	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	5	73	theme	heterozygous	842:853	arg1	parents					855:861	heterozygous parents	842:861	heterozygous parents	842:861	After multiple crosses between heterozygous parents, we were unable to identify homozygous life births in 78 newborn pups (P = 1.59897E-06), suggesting an embryonic lethality phenotype in the homozygotes.
31077402	4	74	theme	tissue-specific	653:667	arg1	phenotypes					677:686	the tissue-specific disease phenotypes	649:686	the tissue-specific disease phenotypes	649:686	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
31077402	3	75	theme	central	541:547	arg1	roles					549:553	the central roles	537:553	the central roles of the enzyme in (glycogen) metabolism and glycosylation	537:610	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	8	76	theme	fibroblasts	1239:1249	arg1	studies					1211:1217	Biochemical studies	1199:1217	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals	1199:1285	Biochemical studies of tissues and skin fibroblasts harvested from heterozygous animals confirmed reduced Pgm2 enzyme activity and abundance, but no change in glycogen content.
31077402	6	77	theme	Ultrasound	1016:1025	arg1	studies					1027:1033	Ultrasound studies	1016:1033	Ultrasound studies of the course of pregnancy	1016:1060	Ultrasound studies of the course of pregnancy confirmed Pgm2-deficient pups succumb before E9.5.
31077402	3	78	theme	severe	349:354	arg1	hypoglycemia					356:367	severe hypoglycemia	349:367	severe hypoglycemia	349:367	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	78	theme	severe	349:354	arg1	hepatopathy					370:380	hepatopathy	370:380	hepatopathy	370:380	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	78	theme	severe	349:354	arg1	deficiencies					412:423	hormonal deficiencies	403:423	hormonal deficiencies	403:423	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	78	theme	severe	349:354	arg1	early-onset					467:477	early-onset	467:477	early-onset of dilated cardiomyopathy and myopathy	467:516	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	78	theme	severe	349:354	arg1	anomalies					437:445	hemostatic anomalies	426:445	hemostatic anomalies	426:445	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	3	78	theme	severe	349:354	arg1	retardation					390:400	growth retardation	383:400	growth retardation	383:400	Overtime, additional clinical phenotypes, which include severe hypoglycemia, hepatopathy, growth retardation, hormonal deficiencies, hemostatic anomalies, frequently lethal, early-onset of dilated cardiomyopathy and myopathy emerge, reflecting the central roles of the enzyme in (glycogen) metabolism and glycosylation.
31077402	2	79	theme	cleft	257:261	arg1	defects					263:269	Midline cleft defects	249:269	Midline cleft defects	249:269	Midline cleft defects are present at birth.
31077402	4	80	theme	constitutive	706:717	arg1	Pgm2					719:722	constitutive Pgm2	706:722	a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model	704:779	To delineate the pathophysiology of the tissue-specific disease phenotypes, we constructed a constitutive Pgm2 (mouse ortholog of human PGM1)-knockout (KO) mouse model using CRISPR-Cas9 technology.
29753740	4	0	dep	Up-regulation	576:588	arg1	6-phosphate					613:623	fructose 6-phosphate	604:623	fructose 6-phosphate aminotransferase 1 (GFAT1)	604:650	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	10	1	theme	proteins	1550:1557	arg1	N-glycosylation					1531:1545	N-glycosylation	1531:1545	N-glycosylation of proteins following the increase of phosphorylation of GFAT1	1531:1608	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	4	2	theme	diphosphate	734:744	arg1	UDP-GlcNAc					767:776	UDP-GlcNAc	767:776	UDP-GlcNAc	767:776	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	4	2	theme	diphosphate	734:744	arg1	N-acetylglucosamine					746:764	uridine diphosphate N-acetylglucosamine	726:764	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein	726:802	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	8	3	theme	increased	1168:1176	arg1	expression					1178:1187	increased expression	1168:1187	increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells	1168:1311	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	9	4	theme	inhibition	1457:1466	arg1	reduction					1404:1412	the reduction	1400:1412	the reduction of protein N-glycosylation and cell growth inhibition	1400:1466	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	3	5	theme	phosphohexose	533:545	arg1	metabolism					547:556	phosphohexose metabolism	533:556	phosphohexose metabolism	533:556	Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated.
29753740	9	6	theme	2DG	1487:1489	arg1	presence					1475:1482	the presence	1471:1482	the presence of 2DG	1471:1489	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	4	7	theme	aminotransferase	625:640	arg1	GFAT1					645:649	aminotransferase 1 (GFAT1)	625:650	fructose 6-phosphate aminotransferase 1 (GFAT1)	604:650	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	0	8	theme	N-glycosylation	129:143	arg1	disruption					107:116	disruption	107:116	disruption of protein N-glycosylation in pancreatic cancer cells	107:170	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	9	9	theme	cell	1445:1448	arg1	inhibition					1457:1466	cell growth inhibition	1445:1466	cell growth inhibition	1445:1466	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	10	10	theme	phosphorylation	1585:1599	arg1	increase					1573:1580	the increase	1569:1580	the increase of phosphorylation of GFAT1	1569:1608	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	9	11	theme	additive	1328:1335	arg1	activation					1337:1346	the additive activation	1324:1346	the additive activation of AMPK by metformin (Met)	1324:1373	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	1	12	theme	cancer	292:297	arg1	lines					304:308	cancer cell lines	292:308	cancer cell lines	292:308	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	0	13	theme	protein	121:127	arg1	N-glycosylation					129:143	protein N-glycosylation	121:143	protein N-glycosylation	121:143	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	4	14	dep	6-phosphate	613:623	arg1	GFAT1					645:649	aminotransferase 1 (GFAT1)	625:650	fructose 6-phosphate aminotransferase 1 (GFAT1)	604:650	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	5	15	gly	N-glycoproteins	905:919	arg1	N-glycoproteins					905:919	total N-glycoproteins	899:919	total N-glycoproteins	899:919	Therefore, we assessed the amounts of total N-glycoproteins.
29753740	6	16	gly	N-glycoproteins	966:980	arg1	N-glycoproteins					966:980	total N-glycoproteins	960:980	total N-glycoproteins	960:980	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	1	17	theme	cell	299:302	arg1	lines					304:308	cancer cell lines	292:308	cancer cell lines	292:308	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	0	18	theme	pancreatic	148:157	arg1	cells					166:170	pancreatic cancer cells	148:170	pancreatic cancer cells	148:170	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	4	19	theme	biosynthesis	685:696	arg1	HBP					707:709	HBP	707:709	HBP	707:709	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	4	19	theme	biosynthesis	685:696	arg1	pathway					698:704	the hexosamine biosynthesis pathway	670:704	the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein	670:802	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	8	20	theme	markers	1202:1208	arg1	expression					1178:1187	increased expression	1168:1187	increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells	1168:1311	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	9	21	theme	AMPK	1351:1354	arg1	activation					1337:1346	the additive activation	1324:1346	the additive activation of AMPK by metformin (Met)	1324:1373	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	9	22	theme	N-glycosylation	1425:1439	arg1	reduction					1404:1412	the reduction	1400:1412	the reduction of protein N-glycosylation and cell growth inhibition	1400:1466	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	5	23	theme	N-glycoproteins	905:919	arg1	amounts					888:894	the amounts	884:894	the amounts of total N-glycoproteins	884:919	Therefore, we assessed the amounts of total N-glycoproteins.
29753740	5	23	theme	N-glycoproteins	905:919	arg1	N-glycoproteins					905:919	total N-glycoproteins	899:919	total N-glycoproteins	899:919	Therefore, we assessed the amounts of total N-glycoproteins.
29753740	2	24	theme	cell	417:420	arg1	line					422:425	pancreatic cancer cell line	399:425	pancreatic cancer cell line	399:425	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	8	25	theme	stress	1195:1200	arg1	protein					1236:1242	glucose response protein 78	1219:1245	glucose response protein 78 (GRP78)	1219:1253	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	25	theme	stress	1195:1200	arg1	protein					1276:1282	C/EBP-homologous protein	1259:1282	C/EBP-homologous protein (CHOP)	1259:1289	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	25	theme	stress	1195:1200	arg1	markers					1202:1208	ER stress markers	1192:1208	ER stress markers	1192:1208	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	10	26	theme	cancer	1691:1696	arg1	cells					1698:1702	pancreatic cancer cells	1680:1702	pancreatic cancer cells	1680:1702	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	10	27	theme	cell	1643:1646	arg1	growth					1648:1653	cell growth	1643:1653	cell growth	1643:1653	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	2	28	theme	cancer	410:415	arg1	line					422:425	pancreatic cancer cell line	399:425	pancreatic cancer cell line	399:425	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	6	29	theme	GFAT1	1005:1009	arg1	phosphorylation					986:1000	phosphorylation	986:1000	phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK)	986:1048	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	6	29	theme	GFAT1	1005:1009	arg1	N-glycoproteins					966:980	total N-glycoproteins	960:980	total N-glycoproteins	960:980	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	6	30	theme	protein	1028:1034	arg1	AMPK					1044:1047	AMPK	1044:1047	AMPK	1044:1047	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	6	30	theme	protein	1028:1034	arg1	kinase					1036:1041	AMP-activated protein kinase	1014:1041	AMP-activated protein kinase (AMPK)	1014:1048	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	2	31	theme	2DG	338:340	arg1	action					328:333	the action	324:333	the action of 2DG in pancreatic cancer	324:361	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	10	32	theme	GFAT1	1604:1608	arg1	phosphorylation					1585:1599	phosphorylation	1585:1599	phosphorylation of GFAT1	1585:1608	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	2	33	theme	pancreatic	399:408	arg1	line					422:425	pancreatic cancer cell line	399:425	pancreatic cancer cell line	399:425	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	1	34	theme	lines	304:308	arg1	range					283:287	a wide range	276:287	a wide range of cancer cell lines	276:308	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	1	35	theme	energy	229:234	arg1	starvation					236:245	energy starvation	229:245	energy starvation	229:245	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	8	36	theme	glucose	1219:1225	arg1	protein					1236:1242	glucose response protein 78	1219:1245	glucose response protein 78 (GRP78)	1219:1253	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	36	theme	glucose	1219:1225	arg1	GRP78					1248:1252	GRP78	1248:1252	GRP78	1248:1252	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	4	37	theme	glutamine	593:601	arg1	Up-regulation					576:588	Up-regulation	576:588	Up-regulation of glutamine	576:601	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	8	38	theme	2DG-treated	1295:1305	arg1	cells					1307:1311	2DG-treated cells	1295:1311	2DG-treated cells	1295:1311	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	10	39	theme	growth	1648:1653	arg1	inhibition					1629:1638	the inhibition	1625:1638	the inhibition of cell growth mediated by ER stress in pancreatic cancer cells	1625:1702	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	9	40	theme	growth	1450:1455	arg1	inhibition					1457:1466	cell growth inhibition	1445:1466	cell growth inhibition	1445:1466	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	10	41	theme	ER	1667:1668	arg1	stress					1670:1675	ER stress	1667:1675	ER stress in pancreatic cancer cells	1667:1702	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	0	42	theme	GFAT1	28:32	arg1	phosphorylation					34:48	GFAT1 phosphorylation	28:48	GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis	28:101	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	0	43	theme	cancer	159:164	arg1	cells					166:170	pancreatic cancer cells	148:170	pancreatic cancer cells	148:170	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	8	44	from	expression	1178:1187	arg1	cells					1307:1311	2DG-treated cells	1295:1311	2DG-treated cells	1295:1311	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	4	45	theme	uridine	726:732	arg1	UDP-GlcNAc					767:776	UDP-GlcNAc	767:776	UDP-GlcNAc	767:776	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	4	45	theme	uridine	726:732	arg1	N-acetylglucosamine					746:764	uridine diphosphate N-acetylglucosamine	726:764	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein	726:802	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	2	46	theme	2DG	433:435	arg1	treatment					437:445	2DG treatment	433:445	2DG treatment	433:445	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	4	47	theme	fructose	604:611	arg1	6-phosphate					613:623	fructose 6-phosphate	604:623	fructose 6-phosphate aminotransferase 1 (GFAT1)	604:650	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	8	48	theme	reticulum	1131:1139	arg1	stress					1146:1151	endoplasmic reticulum (ER) stress	1119:1151	endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells	1119:1311	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	0	49	from	disruption	107:116	arg1	cells					166:170	pancreatic cancer cells	148:170	pancreatic cancer cells	148:170	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	4	50	theme	hexosamine	674:683	arg1	HBP					707:709	HBP	707:709	HBP	707:709	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	4	50	theme	hexosamine	674:683	arg1	pathway					698:704	the hexosamine biosynthesis pathway	670:704	the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein	670:802	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	3	51	theme	Eighty	448:453	arg1	proteins					455:462	Eighty proteins	448:462	Eighty proteins	448:462	Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated.
29753740	3	52	theme	differential	471:482	arg1	expression					484:493	differential expression	471:493	differential expression	471:493	Eighty proteins showed differential expression and among these, proteins involved in phosphohexose metabolism were upregulated.
29753740	8	53	theme	response	1227:1234	arg1	protein					1236:1242	glucose response protein 78	1219:1245	glucose response protein 78 (GRP78)	1219:1253	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	53	theme	response	1227:1234	arg1	GRP78					1248:1252	GRP78	1248:1252	GRP78	1248:1252	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	54	theme	endoplasmic	1119:1129	arg1	ER					1142:1143	ER	1142:1143	ER	1142:1143	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	54	theme	endoplasmic	1119:1129	arg1	reticulum					1131:1139	endoplasmic reticulum	1119:1139	endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells	1119:1311	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	4	55	theme	levels	853:858	arg1	evaluation					822:831	evaluation	822:831	evaluation of mRNA and protein levels	822:858	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	1	56	theme	cell	258:261	arg1	viability					263:271	cell viability	258:271	cell viability	258:271	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	0	57	theme	reticulum-related	75:91	arg1	apoptosis					93:101	endoplasmic reticulum-related apoptosis	63:101	endoplasmic reticulum-related apoptosis	63:101	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	6	58	theme	phosphorylation	986:1000	arg1	reduction					947:955	a reduction	945:955	a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK)	945:1048	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	6	59	theme	AMP-activated	1014:1026	arg1	AMPK					1044:1047	AMPK	1044:1047	AMPK	1044:1047	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	6	59	theme	AMP-activated	1014:1026	arg1	kinase					1036:1041	AMP-activated protein kinase	1014:1041	AMP-activated protein kinase (AMPK)	1014:1048	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	4	60	gly	glycoprotein	791:802	arg1	glycoprotein					791:802	glycoprotein	791:802	glycoprotein	791:802	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	0	61	theme	endoplasmic	63:73	arg1	apoptosis					93:101	endoplasmic reticulum-related apoptosis	63:101	endoplasmic reticulum-related apoptosis	63:101	2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
29753740	7	62	theme	HBP	1080:1082	arg1	dysfunction					1084:1094	HBP dysfunction	1080:1094	HBP dysfunction	1080:1094	These data may shed light on HBP dysfunction.
29753740	6	63	theme	N-glycoproteins	966:980	arg1	reduction					947:955	a reduction	945:955	a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK)	945:1048	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	4	64	theme	mRNA	836:839	arg1	levels					853:858	mRNA and protein levels	836:858	mRNA and protein levels	836:858	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	8	65	theme	C/EBP-homologous	1259:1274	arg1	CHOP					1285:1288	CHOP	1285:1288	CHOP	1285:1288	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	65	theme	C/EBP-homologous	1259:1274	arg1	protein					1276:1282	C/EBP-homologous protein	1259:1282	C/EBP-homologous protein (CHOP)	1259:1289	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	2	66	theme	pancreatic	345:354	arg1	cancer					356:361	pancreatic cancer	345:361	pancreatic cancer	345:361	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	8	67	theme	ER	1192:1193	arg1	protein					1236:1242	glucose response protein 78	1219:1245	glucose response protein 78 (GRP78)	1219:1253	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	67	theme	ER	1192:1193	arg1	protein					1276:1282	C/EBP-homologous protein	1259:1282	C/EBP-homologous protein (CHOP)	1259:1289	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	8	67	theme	ER	1192:1193	arg1	markers					1202:1208	ER stress markers	1192:1208	ER stress markers	1192:1208	Furthermore, we found endoplasmic reticulum (ER) stress accompanied by increased expression of ER stress markers, such as glucose response protein 78 (GRP78) and C/EBP-homologous protein (CHOP), in 2DG-treated cells.
29753740	10	68	from	stress	1670:1675	arg1	cells					1698:1702	pancreatic cancer cells	1680:1702	pancreatic cancer cells	1680:1702	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	1	69	theme	inhibitor	188:196	arg1	2DG					217:219	2DG	217:219	2DG	217:219	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	1	69	theme	inhibitor	188:196	arg1	2-deoxy-d-glucose					198:214	The glycolytic inhibitor 2-deoxy-d-glucose	173:214	The glycolytic inhibitor 2-deoxy-d-glucose (2DG)	173:220	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	2	70	theme	line	422:425	arg1	analysis					387:394	proteomic analysis	377:394	proteomic analysis of pancreatic cancer cell line	377:425	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	4	71	theme	protein	845:851	arg1	levels					853:858	mRNA and protein levels	836:858	mRNA and protein levels	836:858	Up-regulation of glutamine: fructose 6-phosphate aminotransferase 1 (GFAT1), which belongs to the hexosamine biosynthesis pathway (HBP) that produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to maintain glycoprotein, was validated by evaluation of mRNA and protein levels.
29753740	10	72	theme	pancreatic	1680:1689	arg1	cells					1698:1702	pancreatic cancer cells	1680:1702	pancreatic cancer cells	1680:1702	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	1	73	theme	glycolytic	177:186	arg1	2DG					217:219	2DG	217:219	2DG	217:219	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	1	73	theme	glycolytic	177:186	arg1	2-deoxy-d-glucose					198:214	The glycolytic inhibitor 2-deoxy-d-glucose	173:214	The glycolytic inhibitor 2-deoxy-d-glucose (2DG)	173:220	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
29753740	5	74	theme	total	899:903	arg1	N-glycoproteins					905:919	total N-glycoproteins	899:919	total N-glycoproteins	899:919	Therefore, we assessed the amounts of total N-glycoproteins.
29753740	9	75	theme	protein	1417:1423	arg1	N-glycosylation					1425:1439	protein N-glycosylation	1417:1439	protein N-glycosylation	1417:1439	Moreover, the additive activation of AMPK by metformin (Met) synergistically enhanced the reduction of protein N-glycosylation and cell growth inhibition in the presence of 2DG.
29753740	6	76	theme	total	960:964	arg1	N-glycoproteins					966:980	total N-glycoproteins	960:980	total N-glycoproteins	960:980	Unexpectedly, we found a reduction of total N-glycoproteins and phosphorylation of GFAT1 by AMP-activated protein kinase (AMPK).
29753740	10	77	gly	N-glycosylation	1531:1545	arg1	proteins					1550:1557	proteins	1550:1557	proteins following the increase of phosphorylation of GFAT1	1550:1608	These results suggest that 2DG reduces N-glycosylation of proteins following the increase of phosphorylation of GFAT1 and results in the inhibition of cell growth mediated by ER stress in pancreatic cancer cells.
29753740	2	78	theme	proteomic	377:385	arg1	analysis					387:394	proteomic analysis	377:394	proteomic analysis of pancreatic cancer cell line	377:425	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	2	79	from	action	328:333	arg1	cancer					356:361	pancreatic cancer	345:361	pancreatic cancer	345:361	To determine the action of 2DG in pancreatic cancer, we performed proteomic analysis of pancreatic cancer cell line after 2DG treatment.
29753740	1	80	theme	wide	278:281	arg1	range					283:287	a wide range	276:287	a wide range of cancer cell lines	276:308	The glycolytic inhibitor 2-deoxy-d-glucose (2DG) causes energy starvation, affecting cell viability in a wide range of cancer cell lines.
30236981	0	0	theme	close	73:77	arg1	association					79:89	close association	73:89	close association with the ATP/UTP receptor P2Y2	73:120	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	10	1	theme	N-glycosylation	1334:1348	arg1	mutant					1360:1365	The P2Y2R N-glycosylation deficient mutant	1324:1365	The P2Y2R N-glycosylation deficient mutant	1324:1365	The P2Y2R N-glycosylation deficient mutant does not migrate to the cell surface.
30236981	10	2	theme	cell	1391:1394	arg1	surface					1396:1402	the cell surface	1387:1402	the cell surface	1387:1402	The P2Y2R N-glycosylation deficient mutant does not migrate to the cell surface.
30236981	13	3	theme	endoplasmic	1701:1711	arg1	reticulum					1713:1721	the endoplasmic reticulum	1697:1721	the endoplasmic reticulum	1697:1721	These findings demonstrate that in the membrane rafts of the endoplasmic reticulum, both receptors are already closely associated, and B2R shifts into the rafts by affinity with P2Y2R.
30236981	10	4	theme	P2Y2R	1328:1332	arg1	mutant					1360:1365	The P2Y2R N-glycosylation deficient mutant	1324:1365	The P2Y2R N-glycosylation deficient mutant	1324:1365	The P2Y2R N-glycosylation deficient mutant does not migrate to the cell surface.
30236981	6	5	theme	cell	727:730	arg1	surface					732:738	the cell surface	723:738	the cell surface	723:738	After 15 min of UTP stimulation, both receptors almost completely disappeared from the cell surface by endocytosis as observed with a confocal fluorescence microscope.
30236981	8	6	with	stimulation	1023:1033	arg1	GT1b					1054:1057	GT1b	1054:1057	GT1b	1054:1057	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	8	6	with	stimulation	1023:1033	arg1	CSC					1063:1065	CSC	1063:1065	CSC	1063:1065	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	11	7	theme	endoplasmic	1437:1447	arg1	reticulum					1449:1457	the endoplasmic reticulum	1433:1457	the endoplasmic reticulum	1433:1457	It remains predominantly in the endoplasmic reticulum and is fractionated into raft fractions.
30236981	2	8	from	rafts	275:279	arg1	7 cells					288:294	COS 7 cells	284:294	COS 7 cells	284:294	We have shown that most of the P2Y2 receptor (P2Y2R) protein is fractionated into lipid rafts in COS 7 cells.
30236981	9	9	theme	membrane	1308:1315	arg1	rafts					1317:1321	membrane rafts	1308:1321	membrane rafts	1308:1321	Thus, both P2Y2R and B2R migrate into membrane rafts and are endocytosed in parallel with signal crosstalk, clearly indicating that both closely interact on membrane rafts.
30236981	9	10	theme	membrane	1189:1196	arg1	rafts					1198:1202	membrane rafts	1189:1202	membrane rafts	1189:1202	Thus, both P2Y2R and B2R migrate into membrane rafts and are endocytosed in parallel with signal crosstalk, clearly indicating that both closely interact on membrane rafts.
30236981	8	11	from	surface	1142:1148	arg1	disappearance					1083:1095	the disappearance	1079:1095	the disappearance of both P2Y2R and B2R from the cell membrane surface	1079:1148	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	1	12	theme	Several	123:129	arg1	receptors					149:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors are present in lipid rafts.
30236981	0	13	theme	ATP/UTP	100:106	arg1	P2Y2					117:120	the ATP/UTP receptor P2Y2	96:120	the ATP/UTP receptor P2Y2	96:120	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	8	14	theme	membrane	1133:1140	arg1	surface					1142:1148	the cell membrane surface	1124:1148	the cell membrane surface	1124:1148	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	3	15	theme	same	304:307	arg1	cells					309:313	the same cells	300:313	the same cells	300:313	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	8	16	theme	B2R	1115:1117	arg1	disappearance					1083:1095	the disappearance	1079:1095	the disappearance of both P2Y2R and B2R from the cell membrane surface	1079:1148	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	9	17	with	parallel	1227:1234	arg1	crosstalk					1248:1256	signal crosstalk	1241:1256	signal crosstalk	1241:1256	Thus, both P2Y2R and B2R migrate into membrane rafts and are endocytosed in parallel with signal crosstalk, clearly indicating that both closely interact on membrane rafts.
30236981	3	18	theme	protein	365:371	arg1	%					327:327	about 25-30%	316:327	about 25-30% of the bradykinin B2 receptor (B2R) protein	316:371	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	3	18	theme	protein	365:371	arg1	protein					365:371	the bradykinin B2 receptor (B2R) protein	332:371	the bradykinin B2 receptor (B2R) protein	332:371	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	6	19	theme	fluorescence	783:794	arg1	microscope					796:805	a confocal fluorescence microscope	772:805	a confocal fluorescence microscope	772:805	After 15 min of UTP stimulation, both receptors almost completely disappeared from the cell surface by endocytosis as observed with a confocal fluorescence microscope.
30236981	13	20	theme	reticulum	1713:1721	arg1	rafts					1688:1692	the membrane rafts	1675:1692	the membrane rafts of the endoplasmic reticulum	1675:1721	These findings demonstrate that in the membrane rafts of the endoplasmic reticulum, both receptors are already closely associated, and B2R shifts into the rafts by affinity with P2Y2R.
30236981	1	21	theme	lipid	174:178	arg1	rafts					180:184	lipid rafts	174:184	lipid rafts	174:184	Several G protein-coupled receptors are present in lipid rafts.
30236981	8	22	theme	CHO-K1	980:985	arg1	cells					987:991	CHO-K1 cells	980:991	CHO-K1 cells	980:991	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	12	23	dep	mutant	1538:1543	arg1	the					1503:1505	the	1503:1505	the	1503:1505	In the presence of this glycosylation mutant, most of B2R remains in the endoplasmic reticulum, and is fractionated into the raft fraction.
30236981	12	23	dep	mutant	1538:1543	arg1	presence					1507:1514	presence	1507:1514	presence	1507:1514	In the presence of this glycosylation mutant, most of B2R remains in the endoplasmic reticulum, and is fractionated into the raft fraction.
30236981	12	24	theme	glycosylation	1524:1536	arg1	mutant					1538:1543	this glycosylation mutant	1519:1543	this glycosylation mutant	1519:1543	In the presence of this glycosylation mutant, most of B2R remains in the endoplasmic reticulum, and is fractionated into the raft fraction.
30236981	1	25	located	present	163:169	arg2	receptors					149:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors are present in lipid rafts.
30236981	1	25	located	present	163:169	arg1	rafts					180:184	lipid rafts	174:184	lipid rafts	174:184	Several G protein-coupled receptors are present in lipid rafts.
30236981	0	26	theme	raft	23:26	arg1	recruitment					28:38	membrane raft recruitment	14:38	membrane raft recruitment of the bradykinin B2 receptor	14:68	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	8	27	theme	HEK	997:999	arg1	293 cells					1001:1009	HEK 293 cells	997:1009	HEK 293 cells	997:1009	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	0	28	with	association	79:89	arg1	P2Y2					117:120	the ATP/UTP receptor P2Y2	96:120	the ATP/UTP receptor P2Y2	96:120	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	2	29	theme	lipid	269:273	arg1	rafts					275:279	lipid rafts	269:279	lipid rafts in COS 7 cells	269:294	We have shown that most of the P2Y2 receptor (P2Y2R) protein is fractionated into lipid rafts in COS 7 cells.
30236981	7	30	theme	receptors	878:886	arg1	portions					861:868	portions	861:868	portions of both receptors	861:886	Furthermore, with bradykinin stimulation for 15 min, portions of both receptors disappeared from the cell surface and were endocytosed.
30236981	0	31	theme	membrane	14:21	arg1	recruitment					28:38	membrane raft recruitment	14:38	membrane raft recruitment of the bradykinin B2 receptor	14:68	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	13	32	with	affinity	1804:1811	arg1	P2Y2R					1818:1822	P2Y2R	1818:1822	P2Y2R	1818:1822	These findings demonstrate that in the membrane rafts of the endoplasmic reticulum, both receptors are already closely associated, and B2R shifts into the rafts by affinity with P2Y2R.
30236981	0	33	theme	receptor	108:115	arg1	P2Y2					117:120	the ATP/UTP receptor P2Y2	96:120	the ATP/UTP receptor P2Y2	96:120	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	6	34	theme	confocal	774:781	arg1	microscope					796:805	a confocal fluorescence microscope	772:805	a confocal fluorescence microscope	772:805	After 15 min of UTP stimulation, both receptors almost completely disappeared from the cell surface by endocytosis as observed with a confocal fluorescence microscope.
30236981	4	35	theme	raft	530:533	arg1	fraction					535:542	the raft fraction	526:542	the raft fraction	526:542	When both P2Y2R and B2R are co-expressed, the distribution of P2Y2R remained unchanged, but more B2R shifted into the raft fraction.
30236981	3	36	theme	B2	347:348	arg1	B2R					360:362	B2R	360:362	B2R	360:362	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	3	36	theme	B2	347:348	arg1	receptor					350:357	bradykinin B2 receptor	336:357	the bradykinin B2 receptor (B2R) protein	332:371	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	4	37	theme	P2Y2R	474:478	arg1	distribution					458:469	the distribution	454:469	the distribution of P2Y2R	454:478	When both P2Y2R and B2R are co-expressed, the distribution of P2Y2R remained unchanged, but more B2R shifted into the raft fraction.
30236981	1	38	attach	present	163:169	arg2	receptors					149:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors are present in lipid rafts.
30236981	1	38	attach	present	163:169	arg1	rafts					180:184	lipid rafts	174:184	lipid rafts	174:184	Several G protein-coupled receptors are present in lipid rafts.
30236981	5	39	theme	lipid	627:631	arg1	rafts					633:637	the lipid rafts	623:637	the lipid rafts	623:637	This indicates that the interaction between both receptors recruited B2R into the lipid rafts.
30236981	0	40	theme	recruitment	28:38	arg1	Regulation					0:9	Regulation	0:9	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.	0:121	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	9	41	theme	signal	1241:1246	arg1	crosstalk					1248:1256	signal crosstalk	1241:1256	signal crosstalk	1241:1256	Thus, both P2Y2R and B2R migrate into membrane rafts and are endocytosed in parallel with signal crosstalk, clearly indicating that both closely interact on membrane rafts.
30236981	3	42	theme	receptor	350:357	arg1	protein					365:371	the bradykinin B2 receptor (B2R) protein	332:371	the bradykinin B2 receptor (B2R) protein	332:371	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	8	43	theme	P2Y2R	1105:1109	arg1	disappearance					1083:1095	the disappearance	1079:1095	the disappearance of both P2Y2R and B2R from the cell membrane surface	1079:1148	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	13	44	theme	membrane	1679:1686	arg1	rafts					1688:1692	the membrane rafts	1675:1692	the membrane rafts of the endoplasmic reticulum	1675:1721	These findings demonstrate that in the membrane rafts of the endoplasmic reticulum, both receptors are already closely associated, and B2R shifts into the rafts by affinity with P2Y2R.
30236981	0	45	theme	bradykinin	47:56	arg1	receptor					61:68	the bradykinin B2 receptor	43:68	the bradykinin B2 receptor	43:68	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	8	46	theme	cells	1043:1047	arg1	stimulation					1023:1033	continuous stimulation	1012:1033	continuous stimulation of COS7 cells with GT1b and CSC	1012:1065	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	6	47	theme	stimulation	660:670	arg1	15 min					646:651	15 min	646:651	15 min of UTP stimulation	646:670	After 15 min of UTP stimulation, both receptors almost completely disappeared from the cell surface by endocytosis as observed with a confocal fluorescence microscope.
30236981	3	48	theme	bradykinin	336:345	arg1	B2R					360:362	B2R	360:362	B2R	360:362	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	3	48	theme	bradykinin	336:345	arg1	receptor					350:357	bradykinin B2 receptor	336:357	the bradykinin B2 receptor (B2R) protein	332:371	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	8	49	theme	continuous	1012:1021	arg1	stimulation					1023:1033	continuous stimulation	1012:1033	continuous stimulation of COS7 cells with GT1b and CSC	1012:1065	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	6	50	theme	UTP	656:658	arg1	stimulation					660:670	UTP stimulation	656:670	UTP stimulation	656:670	After 15 min of UTP stimulation, both receptors almost completely disappeared from the cell surface by endocytosis as observed with a confocal fluorescence microscope.
30236981	7	51	theme	bradykinin	826:835	arg1	stimulation					837:847	bradykinin stimulation	826:847	bradykinin stimulation for 15 min	826:858	Furthermore, with bradykinin stimulation for 15 min, portions of both receptors disappeared from the cell surface and were endocytosed.
30236981	12	52	theme	raft	1625:1628	arg1	fraction					1630:1637	the raft fraction	1621:1637	the raft fraction	1621:1637	In the presence of this glycosylation mutant, most of B2R remains in the endoplasmic reticulum, and is fractionated into the raft fraction.
30236981	8	53	theme	COS7	1038:1041	arg1	cells					1043:1047	COS7 cells	1038:1047	COS7 cells	1038:1047	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	2	54	theme	P2Y2R	233:237	arg1	protein					240:246	the P2Y2 receptor (P2Y2R) protein	214:246	the P2Y2 receptor (P2Y2R) protein	214:246	We have shown that most of the P2Y2 receptor (P2Y2R) protein is fractionated into lipid rafts in COS 7 cells.
30236981	11	55	theme	raft	1484:1487	arg1	fractions					1489:1497	raft fractions	1484:1497	raft fractions	1484:1497	It remains predominantly in the endoplasmic reticulum and is fractionated into raft fractions.
30236981	3	56	theme	lipid	399:403	arg1	rafts					405:409	lipid rafts	399:409	lipid rafts	399:409	In the same cells, about 25-30% of the bradykinin B2 receptor (B2R) protein is also fractionated into lipid rafts.
30236981	7	57	theme	cell	909:912	arg1	surface					914:920	the cell surface	905:920	the cell surface	905:920	Furthermore, with bradykinin stimulation for 15 min, portions of both receptors disappeared from the cell surface and were endocytosed.
30236981	2	58	theme	COS	284:286	arg1	7 cells					288:294	COS 7 cells	284:294	COS 7 cells	284:294	We have shown that most of the P2Y2 receptor (P2Y2R) protein is fractionated into lipid rafts in COS 7 cells.
30236981	0	59	theme	receptor	61:68	arg1	recruitment					28:38	membrane raft recruitment	14:38	membrane raft recruitment of the bradykinin B2 receptor	14:68	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	10	60	theme	deficient	1350:1358	arg1	mutant					1360:1365	The P2Y2R N-glycosylation deficient mutant	1324:1365	The P2Y2R N-glycosylation deficient mutant	1324:1365	The P2Y2R N-glycosylation deficient mutant does not migrate to the cell surface.
30236981	2	61	theme	receptor	223:230	arg1	protein					240:246	the P2Y2 receptor (P2Y2R) protein	214:246	the P2Y2 receptor (P2Y2R) protein	214:246	We have shown that most of the P2Y2 receptor (P2Y2R) protein is fractionated into lipid rafts in COS 7 cells.
30236981	1	62	from	rafts	180:184	arg1	present					163:169	present	163:169	present	163:169	Several G protein-coupled receptors are present in lipid rafts.
30236981	8	63	theme	cell	1128:1131	arg1	surface					1142:1148	the cell membrane surface	1124:1148	the cell membrane surface	1124:1148	As we reported previously with both CHO-K1 cells and HEK 293 cells, continuous stimulation of COS7 cells with GT1b and CSC resulted in the disappearance of both P2Y2R and B2R from the cell membrane surface.
30236981	0	64	theme	B2	58:59	arg1	receptor					61:68	the bradykinin B2 receptor	43:68	the bradykinin B2 receptor	43:68	Regulation of membrane raft recruitment of the bradykinin B2 receptor by close association with the ATP/UTP receptor P2Y2.
30236981	2	65	theme	P2Y2	218:221	arg1	protein					240:246	the P2Y2 receptor (P2Y2R) protein	214:246	the P2Y2 receptor (P2Y2R) protein	214:246	We have shown that most of the P2Y2 receptor (P2Y2R) protein is fractionated into lipid rafts in COS 7 cells.
30236981	1	66	from	present	163:169	arg1	rafts					180:184	lipid rafts	174:184	lipid rafts	174:184	Several G protein-coupled receptors are present in lipid rafts.
30236981	1	67	theme	protein-coupled	133:147	arg1	receptors					149:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors	123:157	Several G protein-coupled receptors are present in lipid rafts.
30236981	12	68	theme	endoplasmic	1573:1583	arg1	reticulum					1585:1593	the endoplasmic reticulum	1569:1593	the endoplasmic reticulum	1569:1593	In the presence of this glycosylation mutant, most of B2R remains in the endoplasmic reticulum, and is fractionated into the raft fraction.
30061892	4	0	theme	given	498:502	arg1	i.v.					504:507	1 µg given i.v.	493:507	1 µg given i.v. to a mouse	493:518	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	7	1	theme	IC-mediated	865:875	arg1	pathology					877:885	IC-mediated pathology	865:885	IC-mediated pathology	865:885	Thus, EndoS could potentially be used for treating patients with IC-mediated pathology.
30061892	4	2	theme	small	479:483	arg1	sufficient					534:543	sufficient	534:543	sufficient	534:543	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	4	2	theme	small	479:483	arg1	EndoS					524:528	EndoS	524:528	EndoS	524:528	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	4	2	theme	small	479:483	arg1	amount					485:490	A small amount	477:490	A small amount (1 µg given i.v. to a mouse) of EndoS	477:528	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	5	3	theme	EndoS	604:608	arg1	presence					592:599	The presence	588:599	The presence of EndoS	588:608	The presence of EndoS disturbed larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining.
30061892	2	4	theme	IgG	348:350	arg1	γ-chains					336:343	the γ-chains	332:343	the γ-chains of IgG	332:350	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	2	5	from	core	266:269	arg1	297					325:327	the asparagine 297	310:327	the asparagine 297 of the γ-chains of IgG	310:350	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	2	6	theme	Recombinant	205:215	arg1	EndoS					217:221	Recombinant EndoS	205:221	Recombinant EndoS	205:221	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	4	7	theme	1 µg	493:496	arg1	i.v.					504:507	1 µg given i.v.	493:507	1 µg given i.v. to a mouse	493:518	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	5	8	theme	IC	627:628	arg1	formation					638:646	larger IC lattice formation	620:646	larger IC lattice formation both in vitro and in vivo	620:672	The presence of EndoS disturbed larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining.
30061892	5	9	theme	larger	620:625	arg1	formation					638:646	larger IC lattice formation	620:646	larger IC lattice formation both in vitro and in vivo	620:672	The presence of EndoS disturbed larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining.
30061892	2	10	theme	γ-chains	336:343	arg1	297					325:327	the asparagine 297	310:327	the asparagine 297 of the γ-chains of IgG	310:350	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	3	11	theme	arthritis	466:474	arg1	suppression					416:426	suppression	416:426	suppression of local immune complex (IC)-mediated arthritis	416:474	Here, we report that EndoS and IgG hydrolyzed by EndoS induced suppression of local immune complex (IC)-mediated arthritis.
30061892	5	12	theme	lattice	630:636	arg1	formation					638:646	larger IC lattice formation	620:646	larger IC lattice formation both in vitro and in vivo	620:672	The presence of EndoS disturbed larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining.
30061892	0	13	theme	Streptococcal	0:12	arg1	Endo-β-N-Acetylglucosaminidase					14:43	Streptococcal Endo-β-N-Acetylglucosaminidase	0:43	Streptococcal Endo-β-N-Acetylglucosaminidase	0:43	Streptococcal Endo-β-N-Acetylglucosaminidase Suppresses Antibody-Mediated Inflammation In Vivo.
30061892	3	14	theme	local	431:435	arg1	complex					444:450	local immune complex	431:450	local immune complex	431:450	Here, we report that EndoS and IgG hydrolyzed by EndoS induced suppression of local immune complex (IC)-mediated arthritis.
30061892	4	15	theme	IgG-mediated	556:567	arg1	arthritis					569:577	IgG-mediated arthritis	556:577	IgG-mediated arthritis in mice	556:585	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	7	16	used	used	833:836	arg2	EndoS					806:810	EndoS	806:810	EndoS	806:810	Thus, EndoS could potentially be used for treating patients with IC-mediated pathology.
30061892	3	17	theme	-mediated	456:464	arg1	arthritis					466:474	local immune complex (IC)-mediated arthritis	431:474	local immune complex (IC)-mediated arthritis	431:474	Here, we report that EndoS and IgG hydrolyzed by EndoS induced suppression of local immune complex (IC)-mediated arthritis.
30061892	0	18	theme	Antibody-Mediated	56:72	arg1	Inflammation					74:85	Antibody-Mediated Inflammation	56:85	Antibody-Mediated Inflammation	56:85	Streptococcal Endo-β-N-Acetylglucosaminidase Suppresses Antibody-Mediated Inflammation In Vivo.
30061892	4	19	from	arthritis	569:577	arg1	mice					582:585	mice	582:585	mice	582:585	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	1	20	theme	family	140:145	arg1	Endo-β-N-acetylglucosaminidase					96:125	Endo-β-N-acetylglucosaminidase	96:125	Endo-β-N-acetylglucosaminidase (EndoS)	96:133	Endo-β-N-acetylglucosaminidase (EndoS) is a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes.
30061892	1	20	theme	family	140:145	arg1	hydrolase					159:167	a family 18 glycosyl hydrolase	138:167	a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes	138:202	Endo-β-N-acetylglucosaminidase (EndoS) is a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes.
30061892	5	21	theme	anti-C3b	694:701	arg1	staining					703:710	anti-C3b staining	694:710	anti-C3b staining	694:710	The presence of EndoS disturbed larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining.
30061892	2	22	theme	β-1,4-di-N-acetylchitobiose	238:264	arg1	core					266:269	the β-1,4-di-N-acetylchitobiose core	234:269	the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG	234:350	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	2	23	link	N-linked	278:285	arg1	glycan					300:305	the N-linked complex type glycan	274:305	the N-linked complex type glycan	274:305	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	4	24	dep	amount	485:490	arg1	i.v.					504:507	1 µg given i.v.	493:507	1 µg given i.v. to a mouse	493:518	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	2	25	theme	glycan	300:305	arg1	core					266:269	the β-1,4-di-N-acetylchitobiose core	234:269	the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG	234:350	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	3	26	theme	immune	437:442	arg1	complex					444:450	local immune complex	431:450	local immune complex	431:450	Here, we report that EndoS and IgG hydrolyzed by EndoS induced suppression of local immune complex (IC)-mediated arthritis.
30061892	4	27	theme	EndoS	524:528	arg1	sufficient					534:543	sufficient	534:543	sufficient	534:543	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	4	27	theme	EndoS	524:528	arg1	EndoS					524:528	EndoS	524:528	EndoS	524:528	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	4	27	theme	EndoS	524:528	arg1	amount					485:490	A small amount	477:490	A small amount (1 µg given i.v. to a mouse) of EndoS	477:528	A small amount (1 µg given i.v. to a mouse) of EndoS was sufficient to inhibit IgG-mediated arthritis in mice.
30061892	2	28	theme	type	295:298	arg1	glycan					300:305	the N-linked complex type glycan	274:305	the N-linked complex type glycan	274:305	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	6	29	theme	antigen-antibody	753:768	arg1	binding					770:776	antigen-antibody binding	753:776	antigen-antibody binding per se	753:783	Neither complement binding in vitro nor antigen-antibody binding per se were affected.
30061892	1	30	theme	glycosyl	150:157	arg1	Endo-β-N-acetylglucosaminidase					96:125	Endo-β-N-acetylglucosaminidase	96:125	Endo-β-N-acetylglucosaminidase (EndoS)	96:133	Endo-β-N-acetylglucosaminidase (EndoS) is a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes.
30061892	1	30	theme	glycosyl	150:157	arg1	hydrolase					159:167	a family 18 glycosyl hydrolase	138:167	a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes	138:202	Endo-β-N-acetylglucosaminidase (EndoS) is a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes.
30061892	2	31	theme	N-linked	278:285	arg1	glycan					300:305	the N-linked complex type glycan	274:305	the N-linked complex type glycan	274:305	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	2	32	theme	complex	287:293	arg1	glycan					300:305	the N-linked complex type glycan	274:305	the N-linked complex type glycan	274:305	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	3	33	dep	-mediated	456:464	arg1	complex					444:450	local immune complex	431:450	local immune complex	431:450	Here, we report that EndoS and IgG hydrolyzed by EndoS induced suppression of local immune complex (IC)-mediated arthritis.
30061892	7	34	with	patients	851:858	arg1	pathology					877:885	IC-mediated pathology	865:885	IC-mediated pathology	865:885	Thus, EndoS could potentially be used for treating patients with IC-mediated pathology.
30061892	2	35	theme	asparagine	314:323	arg1	297					325:327	the asparagine 297	310:327	the asparagine 297 of the γ-chains of IgG	310:350	Recombinant EndoS hydrolyzes the β-1,4-di-N-acetylchitobiose core of the N-linked complex type glycan on the asparagine 297 of the γ-chains of IgG.
30061892	1	36	theme	Streptococcus	181:193	arg1	pyogenes					195:202	Streptococcus pyogenes	181:202	Streptococcus pyogenes	181:202	Endo-β-N-acetylglucosaminidase (EndoS) is a family 18 glycosyl hydrolase secreted by Streptococcus pyogenes.
30061892	6	37	theme	complement	721:730	arg1	binding					732:738	complement binding	721:738	complement binding in vitro	721:747	Neither complement binding in vitro nor antigen-antibody binding per se were affected.
30790257	0	0	theme	Lipid	85:89	arg1	Activity					102:109	Lipid Scramblase Activity	85:109	Lipid Scramblase Activity	85:109	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	7	1	from	example	1436:1442	arg1	fungus					1491:1496	the fungus Nectria haematococca (nhTMEM16)	1487:1528	the fungus Nectria haematococca (nhTMEM16)	1487:1528	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	2	2	theme	pivotal	383:389	arg1	roles					391:395	pivotal roles	383:395	pivotal roles	383:395	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	1	3	theme	entities	259:266	arg1	action					230:235	the concerted action	216:235	the concerted action of distinct catalytic entities	216:266	The distribution of different lipid species between the two leaflets is tightly regulated and underlies the concerted action of distinct catalytic entities.
30790257	7	4	theme	TMEM16	1464:1469	arg1	scramblase					1471:1480	a Ca2+-activated TMEM16 scramblase	1447:1480	a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16)	1447:1528	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	7	5	from	conclusions	1331:1341	arg1	specificity					1360:1370	the substrate specificity	1346:1370	the substrate specificity	1346:1370	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	7	5	from	conclusions	1331:1341	arg1	kinetics					1383:1390	the kinetics	1379:1390	the kinetics of the transported lipids	1379:1416	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	3	6	theme	members	530:536	arg1	discovery					503:511	The recent discovery	492:511	The recent discovery of TMEM16 family members acting as scramblases	492:558	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	0	7	theme	Activity	102:109	arg1	Measures					73:80	Accurate Measures	64:80	Accurate Measures of Lipid Scramblase Activity	64:109	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	5	8	theme	detergent	1072:1080	arg1	removal					1082:1088	stepwise detergent removal	1063:1088	stepwise detergent removal by adsorption on styryl-beads	1063:1118	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	7	9	theme	scramblase	1471:1480	arg1	example					1436:1442	the example	1432:1442	the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16)	1432:1528	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	2	10	theme	membrane	309:316	arg1	asymmetry					318:326	membrane asymmetry	309:326	membrane asymmetry	309:326	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	0	11	theme	Scramblase	91:100	arg1	Activity					102:109	Lipid Scramblase Activity	85:109	Lipid Scramblase Activity	85:109	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	6	12	theme	reducing	1280:1287	arg1	dithionite					1302:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	7	13	theme	substrate	1350:1358	arg1	specificity					1360:1370	the substrate specificity	1346:1370	the substrate specificity	1346:1370	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	3	14	theme	family	523:528	arg1	members					530:536	TMEM16 family members	516:536	TMEM16 family members	516:536	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	5	15	from	removal	1082:1088	arg1	styryl-beads					1107:1118	styryl-beads	1107:1118	styryl-beads	1107:1118	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	5	16	attach	removal	1082:1088	arg3	styryl-beads					1107:1118	styryl-beads	1107:1118	styryl-beads	1107:1118	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	5	16	attach	removal	1082:1088	arg2	liposomes					1029:1037	liposomes	1029:1037	liposomes using Triton X-100	1029:1056	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	2	17	link	N-linked	456:463	arg1	glycosylation					465:477	N-linked glycosylation	456:477	N-linked glycosylation of proteins	456:489	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	4	18	theme	proteins	814:821	arg1	purification					760:771	purification	760:771	purification	760:771	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	4	18	theme	proteins	814:821	arg1	expression					748:757	expression	748:757	expression	748:757	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	4	18	theme	proteins	814:821	arg1	reconstitution					789:802	functional reconstitution	778:802	functional reconstitution	778:802	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	6	19	theme	selective	1158:1166	arg1	bleaching					1168:1176	the selective bleaching	1154:1176	the selective bleaching of nitrobenzoxadiazol fluorescent lipids	1154:1217	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	5	20	theme	liposomes	980:988	arg1	extrusion					967:975	extrusion	967:975	extrusion of liposomes	967:988	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	4	21	theme	activity	884:891	arg1	liposomes					838:846	preformed liposomes	828:846	preformed liposomes	828:846	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	4	21	theme	activity	884:891	arg1	measurement					852:862	measurement	852:862	measurement of their scrambling activity using fluorescence-labeled lipid derivatives	852:936	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	4	22	theme	TMEM16	807:812	arg1	proteins					814:821	TMEM16 proteins	807:821	TMEM16 proteins	807:821	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	4	23	theme	lipid	920:924	arg1	derivatives					926:936	fluorescence-labeled lipid derivatives	899:936	fluorescence-labeled lipid derivatives	899:936	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	7	24	dep	Nectria	1498:1504	arg1	haematococca					1506:1517	Nectria haematococca	1498:1517	the fungus Nectria haematococca (nhTMEM16)	1487:1528	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	2	25	theme	N-linked	456:463	arg1	glycosylation					465:477	N-linked glycosylation	456:477	N-linked glycosylation of proteins	456:489	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	4	26	theme	fluorescence-labeled	899:918	arg1	derivatives					926:936	fluorescence-labeled lipid derivatives	899:936	fluorescence-labeled lipid derivatives	899:936	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	4	27	dep	expression	748:757	arg1	the					744:746	the	744:746	the	744:746	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	2	28	theme	blood	404:408	arg1	clotting					410:417	blood clotting	404:417	blood clotting	404:417	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	7	29	dep	fungus	1491:1496	arg1	Nectria					1498:1504	Nectria	1498:1504	Nectria	1498:1504	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	7	29	dep	fungus	1491:1496	arg1	nhTMEM16					1520:1527	nhTMEM16	1520:1527	nhTMEM16	1520:1527	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	4	30	theme	functional	778:787	arg1	reconstitution					789:802	functional reconstitution	778:802	functional reconstitution	778:802	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	5	31	theme	Triton	1045:1050	arg1	X-100					1052:1056	Triton X-100	1045:1056	Triton X-100	1045:1056	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	0	32	theme	Proteoliposomes	15:29	arg1	Preparation					0:10	Preparation	0:10	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.	0:110	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	6	33	theme	membrane-impermeant	1260:1278	arg1	dithionite					1302:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	6	34	theme	agent	1289:1293	arg1	dithionite					1302:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	3	35	theme	increasing	574:583	arg1	demand					585:590	an increasing demand	571:590	an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity	571:709	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	6	36	theme	liposomes	1243:1251	arg1	leaflet					1232:1238	the outer leaflet	1222:1238	the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite	1222:1311	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	0	37	theme	TMEM16	45:50	arg1	Protein					52:58	Purified TMEM16 Protein	36:58	Purified TMEM16 Protein	36:58	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	7	38	theme	transported	1399:1409	arg1	lipids					1411:1416	the transported lipids	1395:1416	the transported lipids	1395:1416	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	7	39	from	fungus	1491:1496	arg1	scramblase					1471:1480	a Ca2+-activated TMEM16 scramblase	1447:1480	a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16)	1447:1528	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	7	39	from	fungus	1491:1496	arg1	example					1436:1442	the example	1432:1442	the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16)	1432:1528	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	6	40	theme	scrambling	1125:1134	arg1	assay					1136:1140	The scrambling assay	1121:1140	The scrambling assay	1121:1140	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	0	41	theme	Purified	36:43	arg1	Protein					52:58	Purified TMEM16 Protein	36:58	Purified TMEM16 Protein	36:58	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	3	42	theme	functional	656:665	arg1	investigations					667:680	functional investigations	656:680	functional investigations of their scrambling activity	656:709	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	1	43	theme	concerted	220:228	arg1	action					230:235	the concerted action	216:235	the concerted action of distinct catalytic entities	216:266	The distribution of different lipid species between the two leaflets is tightly regulated and underlies the concerted action of distinct catalytic entities.
30790257	2	44	theme	proteins	482:489	arg1	glycosylation					465:477	N-linked glycosylation	456:477	N-linked glycosylation of proteins	456:489	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	4	45	theme	scrambling	873:882	arg1	activity					884:891	their scrambling activity	867:891	their scrambling activity	867:891	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	6	46	theme	fluorescent	1200:1210	arg1	lipids					1212:1217	nitrobenzoxadiazol fluorescent lipids	1181:1217	nitrobenzoxadiazol fluorescent lipids	1181:1217	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	6	47	theme	outer	1226:1230	arg1	leaflet					1232:1238	the outer leaflet	1222:1238	the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite	1222:1311	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	3	48	theme	recent	496:501	arg1	discovery					503:511	The recent discovery	492:511	The recent discovery of TMEM16 family members acting as scramblases	492:558	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	3	49	theme	TMEM16	516:521	arg1	members					530:536	TMEM16 family members	516:536	TMEM16 family members	516:536	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	5	50	theme	stepwise	1063:1070	arg1	removal					1082:1088	stepwise detergent removal	1063:1088	stepwise detergent removal by adsorption on styryl-beads	1063:1118	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	4	51	theme	preformed	828:836	arg1	liposomes					838:846	preformed liposomes	828:846	preformed liposomes	828:846	Here we describe a protocol for the expression, purification, and functional reconstitution of TMEM16 proteins into preformed liposomes and measurement of their scrambling activity using fluorescence-labeled lipid derivatives.
30790257	0	52	with	Preparation	0:10	arg1	Protein					52:58	Purified TMEM16 Protein	36:58	Purified TMEM16 Protein	36:58	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	1	53	theme	different	132:140	arg1	species					148:154	different lipid species	132:154	different lipid species	132:154	The distribution of different lipid species between the two leaflets is tightly regulated and underlies the concerted action of distinct catalytic entities.
30790257	5	54	theme	liposomes	1029:1037	arg1	removal					1082:1088	stepwise detergent removal	1063:1088	stepwise detergent removal by adsorption on styryl-beads	1063:1118	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	5	54	theme	liposomes	1029:1037	arg1	destabilization					1010:1024	destabilization	1010:1024	destabilization of liposomes using Triton X-100	1010:1056	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	6	55	theme	lipids	1212:1217	arg1	bleaching					1168:1176	the selective bleaching	1154:1176	the selective bleaching of nitrobenzoxadiazol fluorescent lipids	1154:1217	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	3	56	theme	scrambling	691:700	arg1	activity					702:709	their scrambling activity	685:709	their scrambling activity	685:709	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	2	57	gly	glycosylation	465:477	arg1	proteins					482:489	proteins	482:489	proteins	482:489	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	1	58	theme	lipid	142:146	arg1	species					148:154	different lipid species	132:154	different lipid species	132:154	The distribution of different lipid species between the two leaflets is tightly regulated and underlies the concerted action of distinct catalytic entities.
30790257	5	59	from	destabilization	1010:1024	arg1	styryl-beads					1107:1118	styryl-beads	1107:1118	styryl-beads	1107:1118	The reconstitution involves extrusion of liposomes through a membrane, destabilization of liposomes using Triton X-100, and stepwise detergent removal by adsorption on styryl-beads.
30790257	2	60	theme	lipid	355:359	arg1	distribution					361:372	the lipid distribution	351:372	the lipid distribution	351:372	While flippases and floppases establish membrane asymmetry, scramblases randomize the lipid distribution and play pivotal roles during blood clotting, apoptosis, and in processes such as N-linked glycosylation of proteins.
30790257	3	61	theme	activity	702:709	arg1	investigations					667:680	functional investigations	656:680	functional investigations of their scrambling activity	656:709	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	3	62	theme	TMEM16	630:635	arg1	proteins					637:644	TMEM16 proteins	630:644	TMEM16 proteins	630:644	The recent discovery of TMEM16 family members acting as scramblases has led to an increasing demand for developing protocols tailored for TMEM16 proteins to enable functional investigations of their scrambling activity.
30790257	7	63	theme	lipids	1411:1416	arg1	kinetics					1383:1390	the kinetics	1379:1390	the kinetics of the transported lipids	1379:1416	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	1	64	theme	species	148:154	arg1	distribution					116:127	The distribution	112:127	The distribution of different lipid species between the two leaflets	112:179	The distribution of different lipid species between the two leaflets is tightly regulated and underlies the concerted action of distinct catalytic entities.
30790257	1	65	theme	distinct	240:247	arg1	entities					259:266	distinct catalytic entities	240:266	distinct catalytic entities	240:266	The distribution of different lipid species between the two leaflets is tightly regulated and underlies the concerted action of distinct catalytic entities.
30790257	0	66	theme	Accurate	64:71	arg1	Measures					73:80	Accurate Measures	64:80	Accurate Measures of Lipid Scramblase Activity	64:109	Preparation of Proteoliposomes with Purified TMEM16 Protein for Accurate Measures of Lipid Scramblase Activity.
30790257	7	67	theme	Ca2+-activated	1449:1462	arg1	scramblase					1471:1480	a Ca2+-activated TMEM16 scramblase	1447:1480	a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16)	1447:1528	The assay allows conclusions on the substrate specificity and on the kinetics of the transported lipids as shown with the example of a Ca2+-activated TMEM16 scramblase from the fungus Nectria haematococca (nhTMEM16).
30790257	6	68	theme	sodium	1295:1300	arg1	dithionite					1302:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	the membrane-impermeant reducing agent sodium dithionite	1256:1311	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	6	69	theme	nitrobenzoxadiazol	1181:1198	arg1	lipids					1212:1217	nitrobenzoxadiazol fluorescent lipids	1181:1217	nitrobenzoxadiazol fluorescent lipids	1181:1217	The scrambling assay is based on the selective bleaching of nitrobenzoxadiazol fluorescent lipids on the outer leaflet of liposomes by the membrane-impermeant reducing agent sodium dithionite.
30790257	1	70	theme	catalytic	249:257	arg1	entities					259:266	distinct catalytic entities	240:266	distinct catalytic entities	240:266	The distribution of different lipid species between the two leaflets is tightly regulated and underlies the concerted action of distinct catalytic entities.
30682623	0	0	theme	Time	92:95	arg1	Course					97:102	Time Course	92:102	Time Course Omics Analyses	92:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	6	1	theme	sialic	1019:1024	arg1	addition					1031:1038	galactose and sialic acid addition	1005:1038	addition	1031:1038	The steps involving galactose and sialic acid addition were determined as temporal bottlenecks.
30682623	2	2	theme	cell	385:388	arg1	processes					398:406	cell culture processes	385:406	cell culture processes	385:406	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30682623	2	3	from	dial	322:325	arg1	profile					356:362	appropriate glycosylation profile	330:362	appropriate glycosylation profile	330:362	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30682623	7	4	theme	galactosylation	1216:1230	arg1	effectors					1203:1211	known effectors	1197:1211	known effectors of galactosylation	1197:1230	Our results show that galactose, and not manganese, is able to mitigate the temporal bottleneck, despite both being known effectors of galactosylation.
30682623	8	5	theme	monophosphate-sialic	1333:1352	arg1	biosynthesis					1359:1370	cytidine monophosphate-sialic acid biosynthesis	1324:1370	cytidine monophosphate-sialic acid biosynthesis	1324:1370	Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.
30682623	4	6	theme	glycoforms	767:776	arg1	dynamics					755:762	the temporal dynamics	742:762	the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells	742:824	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	4	7	theme	cells	820:824	arg1	cultures					804:811	fed-batch cultures	794:811	fed-batch cultures of CHO cells	794:824	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	0	8	theme	Omics	104:108	arg1	Analyses					110:117	Time Course Omics Analyses	92:117	Time Course Omics Analyses	92:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	6	9	theme	galactose	1005:1013	arg1	addition					1031:1038	galactose and sialic acid addition	1005:1038	addition	1031:1038	The steps involving galactose and sialic acid addition were determined as temporal bottlenecks.
30682623	7	10	theme	known	1197:1201	arg1	effectors					1203:1211	known effectors	1197:1211	known effectors of galactosylation	1197:1230	Our results show that galactose, and not manganese, is able to mitigate the temporal bottleneck, despite both being known effectors of galactosylation.
30682623	5	11	theme	acid	887:890	arg1	cycle					892:896	tricarboxylic citric acid cycle	866:896	tricarboxylic citric acid cycle	866:896	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	3	12	theme	N-glycosylation	429:443	arg1	dynamics					445:452	N-glycosylation dynamics	429:452	N-glycosylation dynamics	429:452	However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases.
30682623	0	13	theme	Course	97:102	arg1	Analyses					110:117	Time Course Omics Analyses	92:117	Time Course Omics Analyses	92:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	4	14	theme	fed-batch	794:802	arg1	cultures					804:811	fed-batch cultures	794:811	fed-batch cultures of CHO cells	794:824	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	5	15	theme	temporal	937:944	arg1	dynamics					946:953	temporal dynamics	937:953	temporal dynamics	937:953	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	4	16	theme	omics	703:707	arg1	analyses					709:716	multi-dimensional omics analyses	685:716	multi-dimensional omics analyses	685:716	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	3	17	theme	sugar	580:584	arg1	donors					597:602	sugar nucleotide donors	580:602	sugar nucleotide donors	580:602	However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases.
30682623	5	18	theme	culture	969:975	arg1	period					977:982	the cell culture period	960:982	the cell culture period	960:982	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	5	19	theme	Several	827:833	arg1	cycle					892:896	tricarboxylic citric acid cycle	866:896	tricarboxylic citric acid cycle	866:896	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	5	19	theme	Several	827:833	arg1	glycolysis					854:863	glycolysis	854:863	glycolysis	854:863	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	5	19	theme	Several	827:833	arg1	pathways					835:842	Several pathways	827:842	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis	827:925	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	5	19	theme	Several	827:833	arg1	biosynthesis					914:925	nucleotide biosynthesis	903:925	nucleotide biosynthesis	903:925	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	5	20	theme	tricarboxylic	866:878	arg1	cycle					892:896	tricarboxylic citric acid cycle	866:896	tricarboxylic citric acid cycle	866:896	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	3	21	theme	nucleotide	586:595	arg1	donors					597:602	sugar nucleotide donors	580:602	sugar nucleotide donors	580:602	However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases.
30682623	5	22	theme	cell	964:967	arg1	period					977:982	the cell culture period	960:982	the cell culture period	960:982	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	0	23	theme	N-Glycosylation	11:25	arg1	Dynamics					27:34	N-Glycosylation Dynamics	11:34	N-Glycosylation Dynamics	11:34	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	2	24	theme	glycosylation	342:354	arg1	profile					356:362	appropriate glycosylation profile	330:362	appropriate glycosylation profile	330:362	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30682623	4	25	theme	temporal	746:753	arg1	dynamics					755:762	the temporal dynamics	742:762	the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells	742:824	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	8	26	theme	galactosylated	1276:1289	arg1	precursors					1291:1300	the galactosylated precursors	1272:1300	the galactosylated precursors	1272:1300	Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.
30682623	2	27	theme	appropriate	330:340	arg1	profile					356:362	appropriate glycosylation profile	330:362	appropriate glycosylation profile	330:362	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30682623	1	28	theme	pharmacokinetic	192:206	arg1	clearance					208:216	pharmacokinetic clearance	192:216	pharmacokinetic clearance	192:216	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	5	29	theme	nucleotide	903:912	arg1	biosynthesis					914:925	nucleotide biosynthesis	903:925	nucleotide biosynthesis	903:925	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	1	30	gly	glycosylation	129:141	arg1	proteins					241:248	several therapeutic proteins	221:248	several therapeutic proteins including monoclonal antibodies	221:280	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	1	30	gly	glycosylation	129:141	arg1	antibodies					271:280	monoclonal antibodies	260:280	monoclonal antibodies	260:280	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	1	31	dep	potency	155:161	arg1	the					151:153	the	151:153	the	151:153	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	3	32	theme	integrative	509:519	arg1	analyses					521:528	integrative analyses	509:528	integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases	509:642	However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases.
30682623	4	33	theme	CHO	816:818	arg1	cells					820:824	CHO cells	816:824	CHO cells	816:824	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	3	34	theme	analyses	521:528	arg1	lack					501:504	the lack	497:504	the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases	497:642	However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases.
30682623	0	35	theme	Hamster	47:53	arg1	Cells					61:65	Chinese Hamster Ovary Cells	39:65	Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses	39:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	6	36	theme	temporal	1059:1066	arg1	steps					989:993	The steps	985:993	The steps involving galactose and sialic acid addition	985:1038	The steps involving galactose and sialic acid addition were determined as temporal bottlenecks.
30682623	6	36	theme	temporal	1059:1066	arg1	bottlenecks					1068:1078	temporal bottlenecks	1059:1078	temporal bottlenecks	1059:1078	The steps involving galactose and sialic acid addition were determined as temporal bottlenecks.
30682623	1	37	theme	several	221:227	arg1	proteins					241:248	several therapeutic proteins	221:248	several therapeutic proteins including monoclonal antibodies	221:280	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	1	37	theme	several	221:227	arg1	antibodies					271:280	monoclonal antibodies	260:280	monoclonal antibodies	260:280	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	0	38	theme	Chinese	39:45	arg1	Cells					61:65	Chinese Hamster Ovary Cells	39:65	Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses	39:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	5	39	theme	citric	880:885	arg1	cycle					892:896	tricarboxylic citric acid cycle	866:896	tricarboxylic citric acid cycle	866:896	Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period.
30682623	4	40	theme	multi-dimensional	685:701	arg1	analyses					709:716	multi-dimensional omics analyses	685:716	multi-dimensional omics analyses	685:716	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	1	41	theme	therapeutic	229:239	arg1	proteins					241:248	several therapeutic proteins	221:248	several therapeutic proteins including monoclonal antibodies	221:280	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	1	41	theme	therapeutic	229:239	arg1	antibodies					271:280	monoclonal antibodies	260:280	monoclonal antibodies	260:280	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	0	42	theme	Cells	61:65	arg1	Cultures					77:84	Chinese Hamster Ovary Cells Fed-batch Cultures	39:84	Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses	39:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	1	43	theme	N-linked	120:127	arg1	glycosylation					129:141	N-linked glycosylation	120:141	N-linked glycosylation	120:141	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	0	44	theme	Ovary	55:59	arg1	Cells					61:65	Chinese Hamster Ovary Cells	39:65	Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses	39:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	7	45	theme	temporal	1157:1164	arg1	bottleneck					1166:1175	the temporal bottleneck	1153:1175	the temporal bottleneck	1153:1175	Our results show that galactose, and not manganese, is able to mitigate the temporal bottleneck, despite both being known effectors of galactosylation.
30682623	8	46	theme	cytidine	1324:1331	arg1	biosynthesis					1359:1370	cytidine monophosphate-sialic acid biosynthesis	1324:1370	cytidine monophosphate-sialic acid biosynthesis	1324:1370	Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.
30682623	1	47	link	N-linked	120:127	arg1	glycosylation					129:141	N-linked glycosylation	120:141	N-linked glycosylation	120:141	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	2	48	theme	control	292:298	arg1	strategy					300:307	A robust control strategy	283:307	A robust control strategy	283:307	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30682623	1	49	theme	proteins	241:248	arg1	immunogenicity					172:185	immunogenicity	172:185	immunogenicity	172:185	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	1	49	theme	proteins	241:248	arg1	safety					164:169	safety	164:169	safety	164:169	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	1	49	theme	proteins	241:248	arg1	clearance					208:216	pharmacokinetic clearance	192:216	pharmacokinetic clearance	192:216	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	1	49	theme	proteins	241:248	arg1	potency					155:161	potency	155:161	potency	155:161	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	2	50	theme	robust	285:290	arg1	strategy					300:307	A robust control strategy	283:307	A robust control strategy	283:307	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30682623	3	51	theme	factors	533:539	arg1	analyses					521:528	integrative analyses	509:528	integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases	509:642	However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases.
30682623	8	52	theme	acid	1354:1357	arg1	biosynthesis					1359:1370	cytidine monophosphate-sialic acid biosynthesis	1324:1370	cytidine monophosphate-sialic acid biosynthesis	1324:1370	Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.
30682623	4	53	theme	integrative	654:664	arg1	approach					666:673	an integrative approach	651:673	an integrative approach involving multi-dimensional omics analyses	651:716	Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells.
30682623	2	54	theme	processes	398:406	arg1	course					375:380	the course	371:380	the course of cell culture processes	371:406	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30682623	8	55	theme	biosynthesis	1359:1370	arg1	autoregulation					1306:1319	autoregulation	1306:1319	autoregulation of cytidine monophosphate-sialic acid biosynthesis	1306:1370	Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.
30682623	8	55	theme	biosynthesis	1359:1370	arg1	precursors					1291:1300	the galactosylated precursors	1272:1300	the galactosylated precursors	1272:1300	Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.
30682623	1	56	theme	monoclonal	260:269	arg1	antibodies					271:280	monoclonal antibodies	260:280	monoclonal antibodies	260:280	N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies.
30682623	0	57	theme	Fed-batch	67:75	arg1	Cultures					77:84	Chinese Hamster Ovary Cells Fed-batch Cultures	39:84	Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses	39:117	Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
30682623	6	58	theme	acid	1026:1029	arg1	addition					1031:1038	galactose and sialic acid addition	1005:1038	addition	1031:1038	The steps involving galactose and sialic acid addition were determined as temporal bottlenecks.
30682623	2	59	theme	culture	390:396	arg1	processes					398:406	cell culture processes	385:406	cell culture processes	385:406	A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately.
30101988	3	0	theme	aging	1044:1048	arg1	they					880:883	they	880:883	they	880:883	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	0	theme	aging	1044:1048	arg1	markers					1050:1056	aging markers	1044:1056	aging markers	1044:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	4	1	theme	carbohydrate	1223:1234	arg1	decomposition					1236:1248	the N-linked carbohydrate decomposition	1210:1248	the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1210:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	0	2	theme	G1	165:166	arg1	N-glycosylation					125:139	the N-glycosylation	121:139	the N-glycosylation of human immunoglobulin G1	121:166	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	1	3	theme	paper	475:479	arg1	aspects					460:466	the important messaging aspects	436:466	the important messaging aspects of our paper	436:479	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	1	4	dep	G1	401:402	arg1	[1					404:405	[1	404:405	[1	404:405	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	0	5	theme	Electrophoresis	51:65	arg1	journal					40:46	the journal	36:46	the journal of Electrophoresis	36:65	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	4	6	theme	IgG	1253:1255	arg1	molecules					1264:1272	IgG type 1 molecules	1253:1272	IgG type 1 molecules	1253:1272	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	0	7	theme	immunoglobulin	150:163	arg1	G1					165:166	human immunoglobulin G1	144:166	human immunoglobulin G1	144:166	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	3	8	theme	space	782:786	arg1	radiation					788:796	simulated space radiation	772:796	simulated space radiation	772:796	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	9	theme	longer	932:937	arg1	missions					945:952	longer space missions	932:952	longer space missions	932:952	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	2	10	theme	space	645:649	arg1	goal					685:688	the goal	681:688	the goal of this paper	681:702	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	2	10	theme	space	645:649	arg1	description					661:671	complete space radiation description	636:671	complete space radiation description	636:671	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	3	11	theme	disease	906:912	arg1	they					880:883	they	880:883	they	880:883	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	11	theme	disease	906:912	arg1	biomarkers					914:923	disease biomarkers	906:923	disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease	906:1039	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	12	theme	molecules	839:847	arg1	N-glycosylation					815:829	the conserved N-glycosylation	801:829	the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	801:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	1	13	theme	Bevelacqua	239:248	arg1	commentary					225:234	the commentary	221:234	the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1]	221:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	3	14	theme	radiation	788:796	arg1	effect					762:767	the effect	758:767	the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	758:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	1	15	theme	simulated	328:336	arg1	radiation					344:352	simulated space radiation	328:352	simulated space radiation	328:352	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	4	16	theme	N-linked	1214:1221	arg1	decomposition					1236:1248	the N-linked carbohydrate decomposition	1210:1248	the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1210:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	3	17	theme	IgG1	834:837	arg1	molecules					839:847	IgG1 molecules	834:847	IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	834:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	18	used	used	993:996	arg2	they					974:977	they	974:977	they	974:977	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	1	19	theme	space	338:342	arg1	radiation					344:352	simulated space radiation	328:352	simulated space radiation	328:352	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	3	20	theme	conserved	805:813	arg1	N-glycosylation					815:829	the conserved N-glycosylation	801:829	the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	801:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	1	21	theme	radiation	344:352	arg1	effect					318:323	The effect	314:323	The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1]	314:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	3	22	theme	similar	955:961	arg1	missions					945:952	longer space missions	932:952	longer space missions	932:952	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	4	23	theme	irradiation	1195:1205	arg1	effects					1177:1183	the qualitative effects	1161:1183	the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1161:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	3	24	dep	that	966:969	arg1	used					993:996	used	993:996	are currently used here on Earth	979:1010	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	25	theme	space	939:943	arg1	missions					945:952	longer space missions	932:952	longer space missions	932:952	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	26	from	effect	762:767	arg1	N-glycosylation					815:829	the conserved N-glycosylation	801:829	the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	801:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	4	27	theme	biological	1104:1113	arg1	effects					1115:1121	any biological effects	1100:1121	any biological effects	1100:1121	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	1	28	dep	scientists	594:603	arg1	i.e.					573:576	i.e.	573:576	i.e.	573:576	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	1	29	theme	separation	583:592	arg1	scientists					594:603	not separation scientists	579:603	not separation scientists	579:603	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	1	30	theme	Mortazavi	254:262	arg1	commentary					225:234	the commentary	221:234	the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1]	221:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	0	31	theme	space	102:106	arg1	radiation					108:116	simulated space radiation	92:116	simulated space radiation	92:116	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	0	32	theme	simulated	92:100	arg1	radiation					108:116	simulated space radiation	92:116	simulated space radiation	92:116	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	3	33	with	molecules	839:847	arg1	goal					858:861	the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	854:1056	the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	854:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	2	34	theme	paper	698:702	arg1	goal					685:688	the goal	681:688	the goal of this paper	681:702	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	2	34	theme	paper	698:702	arg1	description					661:671	complete space radiation description	636:671	complete space radiation description	636:671	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	4	35	theme	space	1346:1350	arg1	travel					1352:1357	deep space travel	1341:1357	deep space travel	1341:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	4	36	from	effects	1177:1183	arg1	decomposition					1236:1248	the N-linked carbohydrate decomposition	1210:1248	the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1210:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	4	37	theme	qualitative	1165:1175	arg1	effects					1177:1183	the qualitative effects	1161:1183	the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1161:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	4	38	dep	given	1088:1092	arg1	investigated					1148:1159	investigated	1148:1159	investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1148:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	4	38	dep	given	1088:1092	arg1	either					1123:1128	either	1123:1128	either	1123:1128	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	1	39	from	effect	318:323	arg1	N-glycosylation					361:375	the N-glycosylation	357:375	the N-glycosylation of human immunoglobulin G1"[1]	357:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	4	40	link	N-linked	1214:1221	arg1	decomposition					1236:1248	the N-linked carbohydrate decomposition	1210:1248	the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1210:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	0	41	theme	radiation	108:116	arg1	effect					82:87	The effect	78:87	"The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi	77:207	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	4	42	theme	proton	1188:1193	arg1	irradiation					1195:1205	proton irradiation	1188:1205	proton irradiation	1188:1205	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	2	43	theme	complete	636:643	arg1	goal					685:688	the goal	681:688	the goal of this paper	681:702	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	2	43	theme	complete	636:643	arg1	description					661:671	complete space radiation description	636:671	complete space radiation description	636:671	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	1	44	theme	published	287:295	arg1	paper					297:301	our recently published paper	274:301	our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1]	274:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	4	45	theme	type	1257:1260	arg1	molecules					1264:1272	IgG type 1 molecules	1253:1272	IgG type 1 molecules	1253:1272	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	0	46	from	Commentary	22:31	arg1	journal					40:46	the journal	36:46	the journal of Electrophoresis	36:65	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	4	47	used	used	1315:1318	arg2	them					1304:1307	them	1304:1307	them	1304:1307	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	4	47	used	used	1315:1318	arg2	biomarkers					1323:1332	biomarkers	1323:1332	biomarkers	1323:1332	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	1	48	theme	human	380:384	arg1	G1					401:402	human immunoglobulin G1	380:402	human immunoglobulin G1"[1]	380:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	1	49	theme	immunoglobulin	386:399	arg1	G1					401:402	human immunoglobulin G1	380:402	human immunoglobulin G1"[1]	380:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	1	50	theme	important	440:448	arg1	aspects					460:466	the important messaging aspects	436:466	the important messaging aspects of our paper	436:479	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	4	51	theme	molecules	1264:1272	arg1	decomposition					1236:1248	the N-linked carbohydrate decomposition	1210:1248	the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel	1210:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	0	52	theme	human	144:148	arg1	G1					165:166	human immunoglobulin G1	144:166	human immunoglobulin G1	144:166	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	0	53	from	effect	82:87	arg1	N-glycosylation					125:139	the N-glycosylation	121:139	the N-glycosylation of human immunoglobulin G1	121:166	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	1	54	theme	messaging	450:458	arg1	aspects					460:466	the important messaging aspects	436:466	the important messaging aspects of our paper	436:479	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	4	55	with	decomposition	1236:1248	arg1	intent					1283:1288	the intent	1279:1288	the intent of suggesting them to be used as biomarkers during deep space travel	1279:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	3	56	gly	N-glycosylation	815:829	arg1	molecules					839:847	IgG1 molecules	834:847	IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers	834:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	57	theme	autoimmune	1022:1031	arg1	disease					1033:1039	autoimmune disease	1022:1039	autoimmune disease	1022:1039	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	1	58	theme	G1	401:402	arg1	N-glycosylation					361:375	the N-glycosylation	357:375	the N-glycosylation of human immunoglobulin G1"[1]	357:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	3	59	used	utilized	894:901	arg2	they					880:883	they	880:883	they	880:883	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	59	used	utilized	894:901	arg2	markers					1050:1056	aging markers	1044:1056	aging markers	1044:1056	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	3	59	used	utilized	894:901	arg2	biomarkers					914:923	disease biomarkers	906:923	disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease	906:1039	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	5	60	from	issue	1389:1393	arg1	study					1402:1406	our study	1398:1406	our study	1398:1406	Radioadaptation was never an issue in our study for the reasons mentioned above.
30101988	1	61	gly	N-glycosylation	361:375	arg1	G1					401:402	human immunoglobulin G1	380:402	human immunoglobulin G1"[1]	380:406	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	4	62	theme	deep	1341:1344	arg1	travel					1352:1357	deep space travel	1341:1357	deep space travel	1341:1357	Therefore, no discussion was given about any biological effects either as our study only investigated the qualitative effects of proton irradiation on the N-linked carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting them to be used as biomarkers during deep space travel.
30101988	3	63	theme	short	713:717	arg1	communication					719:731	this short communication	708:731	this short communication	708:731	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30101988	2	64	theme	radiation	651:659	arg1	goal					685:688	the goal	681:688	the goal of this paper	681:702	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	2	64	theme	radiation	651:659	arg1	description					661:671	complete space radiation description	636:671	complete space radiation description	636:671	First, we should clarify that complete space radiation description was not the goal of this paper.
30101988	0	65	gly	N-glycosylation	125:139	arg1	G1					165:166	human immunoglobulin G1	144:166	human immunoglobulin G1	144:166	Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
30101988	1	66	theme	wider	557:561	arg1	audience					563:570	a wider audience	555:570	a wider audience	555:570	By reading the commentary of Bevelacqua and Mortazavi regarding our recently published paper titled as "The effect of simulated space radiation on the N-glycosylation of human immunoglobulin G1"[1], we are afraid that some of the important messaging aspects of our paper might not have been articulated adequately to be fully understandable for a wider audience, i.e., not separation scientists.
30101988	3	67	theme	simulated	772:780	arg1	radiation					788:796	simulated space radiation	772:796	simulated space radiation	772:796	In this short communication we only intended to show the effect of simulated space radiation on the conserved N-glycosylation of IgG1 molecules with the goal to understand if they could be utilized as disease biomarkers during longer space missions, similar to that as they are currently used here on Earth, e.g. for autoimmune disease or aging markers.
30008906	7	0	theme	aforementioned	1008:1021	arg1	result					1023:1028	the aforementioned result	1004:1028	the aforementioned result	1004:1028	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	6	1	theme	signaling	969:977	arg1	pathway					979:985	the protein kinase B (AKT) signaling pathway	942:985	the protein kinase B (AKT) signaling pathway	942:985	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	6	2	theme	FUT8	805:808	arg1	role					797:800	the role	793:800	the role of FUT8 in MCF10A cells	793:824	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	2	3	theme	cancer	341:346	arg1	progression					348:358	cancer progression	341:358	cancer progression	341:358	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	2	4	theme	important	265:273	arg1	core-fucosylation					241:257	Protein core-fucosylation	233:257	Protein core-fucosylation	233:257	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	2	4	theme	important	265:273	arg1	modification					298:309	an important N-linked glycosylation modification	262:309	an important N-linked glycosylation modification	262:309	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	2	5	theme	N-linked	275:282	arg1	core-fucosylation					241:257	Protein core-fucosylation	233:257	Protein core-fucosylation	233:257	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	2	5	theme	N-linked	275:282	arg1	modification					298:309	an important N-linked glycosylation modification	262:309	an important N-linked glycosylation modification	262:309	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	6	6	theme	AKT	964:966	arg1	pathway					979:985	the protein kinase B (AKT) signaling pathway	942:985	the protein kinase B (AKT) signaling pathway	942:985	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	8	7	theme	breast	1364:1369	arg1	cells					1378:1382	breast cancer cells	1364:1382	breast cancer cells	1364:1382	To conclude, the findings from the present study indicate that miR-10b promotes motility and proliferation by increasing FUT8 and activating AKT in breast cancer cells.
30008906	5	8	theme	miR-10b-overexpressed	723:743	arg1	cells					752:756	miR-10b-overexpressed MCF10A cells	723:756	miR-10b-overexpressed MCF10A cells	723:756	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	3	9	theme	MCF10A	488:493	arg1	cells					495:499	miR-10b-overexpressed MCF10A cells	466:499	miR-10b-overexpressed MCF10A cells	466:499	In a previous study, a glycogene array was applied to profile the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells.
30008906	2	10	from	roles	332:336	arg1	progression					348:358	cancer progression	341:358	cancer progression	341:358	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	8	11	theme	cancer	1371:1376	arg1	cells					1378:1382	breast cancer cells	1364:1382	breast cancer cells	1364:1382	To conclude, the findings from the present study indicate that miR-10b promotes motility and proliferation by increasing FUT8 and activating AKT in breast cancer cells.
30008906	6	12	from	role	797:800	arg1	cells					820:824	MCF10A cells	813:824	MCF10A cells	813:824	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	5	13	theme	MCF10A	745:750	arg1	cells					752:756	miR-10b-overexpressed MCF10A cells	723:756	miR-10b-overexpressed MCF10A cells	723:756	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	7	14	theme	miR-10b	1087:1093	arg1	expression					1095:1104	miR-10b expression	1087:1104	miR-10b expression	1087:1104	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	1	15	theme	miR-10b	191:197	arg1	role					183:186	the role	179:186	the role of miR-10b in glycosylation	179:214	Upregulation of microRNA (miR)-10b has been confirmed in multiple types of cancer, however, the role of miR-10b in glycosylation remains unclear.
30008906	7	16	theme	MCF10A	1202:1207	arg1	cells					1209:1213	Twist-overexpressed MCF10A cells	1182:1213	Twist-overexpressed MCF10A cells	1182:1213	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	0	17	from	axis	58:61	arg1	cells					80:84	breast cancer cells	66:84	breast cancer cells	66:84	Enhanced motility and proliferation by miR-10b/FUT8/p-AKT axis in breast cancer cells.
30008906	1	18	theme	cancer	162:167	arg1	types					153:157	multiple types	144:157	multiple types of cancer	144:167	Upregulation of microRNA (miR)-10b has been confirmed in multiple types of cancer, however, the role of miR-10b in glycosylation remains unclear.
30008906	7	19	theme	Twist-overexpressed	1182:1200	arg1	cells					1209:1213	Twist-overexpressed MCF10A cells	1182:1213	Twist-overexpressed MCF10A cells	1182:1213	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	6	20	theme	B	961:961	arg1	pathway					979:985	the protein kinase B (AKT) signaling pathway	942:985	the protein kinase B (AKT) signaling pathway	942:985	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	8	21	theme	present	1251:1257	arg1	study					1259:1263	the present study	1247:1263	the present study	1247:1263	To conclude, the findings from the present study indicate that miR-10b promotes motility and proliferation by increasing FUT8 and activating AKT in breast cancer cells.
30008906	4	22	theme	core-fucose	580:590	arg1	addition					568:575	the addition	564:575	the addition of core-fucose to N-glycan	564:602	Notably, fucosyltranferase 8 (FUT8), which is responsible for the addition of core-fucose to N-glycan, was significantly upregulated by miR-10b.
30008906	6	23	theme	kinase	954:959	arg1	pathway					979:985	the protein kinase B (AKT) signaling pathway	942:985	the protein kinase B (AKT) signaling pathway	942:985	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	2	24	theme	glycosylation	284:296	arg1	core-fucosylation					241:257	Protein core-fucosylation	233:257	Protein core-fucosylation	233:257	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	2	24	theme	glycosylation	284:296	arg1	modification					298:309	an important N-linked glycosylation modification	262:309	an important N-linked glycosylation modification	262:309	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	3	25	theme	glycogene	442:450	arg1	expression					452:461	glycogene expression	442:461	glycogene expression	442:461	In a previous study, a glycogene array was applied to profile the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells.
30008906	3	26	theme	previous	366:373	arg1	study					375:379	a previous study	364:379	a previous study	364:379	In a previous study, a glycogene array was applied to profile the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells.
30008906	6	27	theme	protein	946:952	arg1	pathway					979:985	the protein kinase B (AKT) signaling pathway	942:985	the protein kinase B (AKT) signaling pathway	942:985	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	1	28	theme	multiple	144:151	arg1	types					153:157	multiple types	144:157	multiple types of cancer	144:167	Upregulation of microRNA (miR)-10b has been confirmed in multiple types of cancer, however, the role of miR-10b in glycosylation remains unclear.
30008906	3	29	theme	expression	452:461	arg1	alterations					427:437	the alterations	423:437	the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells	423:499	In a previous study, a glycogene array was applied to profile the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells.
30008906	0	30	theme	miR-10b/FUT8/p-AKT	39:56	arg1	axis					58:61	miR-10b/FUT8/p-AKT axis	39:61	miR-10b/FUT8/p-AKT axis in breast cancer cells	39:84	Enhanced motility and proliferation by miR-10b/FUT8/p-AKT axis in breast cancer cells.
30008906	7	31	theme	decreased	1031:1039	arg1	motility					1041:1048	decreased motility	1031:1048	decreased motility	1031:1048	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	7	32	theme	transforming	1141:1152	arg1	factor-β-induced					1161:1176	transforming growth factor-β-induced	1141:1176	transforming growth factor-β-induced	1141:1176	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	7	33	theme	growth	1154:1159	arg1	factor-β-induced					1161:1176	transforming growth factor-β-induced	1141:1176	transforming growth factor-β-induced	1141:1176	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	3	34	from	alterations	427:437	arg1	cells					495:499	miR-10b-overexpressed MCF10A cells	466:499	miR-10b-overexpressed MCF10A cells	466:499	In a previous study, a glycogene array was applied to profile the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells.
30008906	7	35	theme	MDA-MB-231	1123:1132	arg1	cells					1134:1138	MDA-MB-231 cells	1123:1138	MDA-MB-231 cells	1123:1138	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	2	36	link	N-linked	275:282	arg1	core-fucosylation					241:257	Protein core-fucosylation	233:257	Protein core-fucosylation	233:257	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	2	36	link	N-linked	275:282	arg1	modification					298:309	an important N-linked glycosylation modification	262:309	an important N-linked glycosylation modification	262:309	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	5	37	theme	present	654:660	arg1	study					662:666	the present study	650:666	the present study	650:666	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	1	38	from	role	183:186	arg1	glycosylation					202:214	glycosylation	202:214	glycosylation	202:214	Upregulation of microRNA (miR)-10b has been confirmed in multiple types of cancer, however, the role of miR-10b in glycosylation remains unclear.
30008906	1	39	theme	miR	113:115	arg1	-10b					117:120	microRNA (miR)-10b	103:120	microRNA (miR)-10b	103:120	Upregulation of microRNA (miR)-10b has been confirmed in multiple types of cancer, however, the role of miR-10b in glycosylation remains unclear.
30008906	3	40	theme	glycogene	384:392	arg1	array					394:398	a glycogene array	382:398	a glycogene array	382:398	In a previous study, a glycogene array was applied to profile the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells.
30008906	2	41	theme	Protein	233:239	arg1	core-fucosylation					241:257	Protein core-fucosylation	233:257	Protein core-fucosylation	233:257	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	2	41	theme	Protein	233:239	arg1	modification					298:309	an important N-linked glycosylation modification	262:309	an important N-linked glycosylation modification	262:309	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	1	42	theme	-10b	117:120	arg1	Upregulation					87:98	Upregulation	87:98	Upregulation of microRNA (miR)-10b	87:120	Upregulation of microRNA (miR)-10b has been confirmed in multiple types of cancer, however, the role of miR-10b in glycosylation remains unclear.
30008906	1	43	theme	microRNA	103:110	arg1	-10b					117:120	microRNA (miR)-10b	103:120	microRNA (miR)-10b	103:120	Upregulation of microRNA (miR)-10b has been confirmed in multiple types of cancer, however, the role of miR-10b in glycosylation remains unclear.
30008906	7	44	with	Consistent	988:997	arg1	result					1023:1028	the aforementioned result	1004:1028	the aforementioned result	1004:1028	Consistent with the aforementioned result, decreased motility and proliferation were detected when miR-10b expression was inhibited in MDA-MB-231 cells, transforming growth factor-β-induced and Twist-overexpressed MCF10A cells.
30008906	5	45	theme	increased	669:677	arg1	motility					679:686	motility	679:686	motility	679:686	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	6	46	theme	MCF10A	813:818	arg1	cells					820:824	MCF10A cells	813:824	MCF10A cells	813:824	To assess the mechanism involved, the role of FUT8 in MCF10A cells was studied and it was confirmed that miR-10b promotes motility and proliferation by regulating FUT8 and activating the protein kinase B (AKT) signaling pathway.
30008906	8	47	from	study	1259:1263	arg1	findings					1233:1240	the findings	1229:1240	the findings from the present study	1229:1263	To conclude, the findings from the present study indicate that miR-10b promotes motility and proliferation by increasing FUT8 and activating AKT in breast cancer cells.
30008906	3	48	theme	miR-10b-overexpressed	466:486	arg1	cells					495:499	miR-10b-overexpressed MCF10A cells	466:499	miR-10b-overexpressed MCF10A cells	466:499	In a previous study, a glycogene array was applied to profile the alterations of glycogene expression in miR-10b-overexpressed MCF10A cells.
30008906	2	49	theme	important	322:330	arg1	roles					332:336	important roles	322:336	important roles in cancer progression	322:358	Protein core-fucosylation is an important N-linked glycosylation modification and serves important roles in cancer progression.
30008906	0	50	theme	cancer	73:78	arg1	cells					80:84	breast cancer cells	66:84	breast cancer cells	66:84	Enhanced motility and proliferation by miR-10b/FUT8/p-AKT axis in breast cancer cells.
30008906	5	51	located	observed	711:718	arg2	proliferation					692:704	proliferation	692:704	proliferation	692:704	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	5	51	located	observed	711:718	arg1	study					662:666	the present study	650:666	the present study	650:666	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	5	51	located	observed	711:718	arg1	cells					752:756	miR-10b-overexpressed MCF10A cells	723:756	miR-10b-overexpressed MCF10A cells	723:756	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	5	51	located	observed	711:718	arg2	motility					679:686	motility	679:686	motility	679:686	In the present study, increased motility and proliferation were observed in miR-10b-overexpressed MCF10A cells.
30008906	8	52	from	AKT	1357:1359	arg1	cells					1378:1382	breast cancer cells	1364:1382	breast cancer cells	1364:1382	To conclude, the findings from the present study indicate that miR-10b promotes motility and proliferation by increasing FUT8 and activating AKT in breast cancer cells.
30008906	0	53	theme	breast	66:71	arg1	cells					80:84	breast cancer cells	66:84	breast cancer cells	66:84	Enhanced motility and proliferation by miR-10b/FUT8/p-AKT axis in breast cancer cells.
31056222	2	0	dep	USA	562:564	arg1	BM					543:544	Biomend, BM, Zimmer Biomet, USA	534:564	BM	543:544	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	0	dep	USA	562:564	arg1	Zimmer					547:552	Zimmer	547:552	Zimmer	547:552	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	17	1	theme	collagen	2402:2409	arg1	membrane					2411:2418	the collagen membrane	2398:2418	the collagen membrane cross-linked with polysaccharides	2398:2452	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	14	2	dep	BM	2020:2021	arg1	the					2016:2018	the	2016:2018	the	2016:2018	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	1	3	theme	in-vitro	276:283	arg1	membranes					266:274	these membranes	260:274	these membranes in-vitro	260:283	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	17	4	from	DM	2516:2517	arg1	membrane					2527:2534	membrane	2527:2534	membrane	2527:2534	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	17	4	from	DM	2516:2517	arg1	tests					2547:2551	eluate tests	2540:2551	eluate tests	2540:2551	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	7	5	theme	cell	1249:1252	arg1	proliferation					1254:1266	the cell proliferation	1245:1266	the cell proliferation of adherent cells	1245:1284	The highest impact was observed for DM, its eluate doubled the cell proliferation of adherent cells when compared to the control (p<0.001).
31056222	2	6	theme	stem	312:315	arg1	hMSCs					324:328	hMSCs	324:328	hMSCs	324:328	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	6	theme	stem	312:315	arg1	cells					317:321	Human mesenchymal stem cells	294:321	Human mesenchymal stem cells (hMSCs)	294:329	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	6	theme	stem	312:315	arg1	PDL-hTERTs					381:390	PDL-hTERTs	381:390	PDL-hTERTs	381:390	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	13	7	contain	have	1927:1930	arg1	the					1839:1841	the	1839:1841	the	1839:1841	Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome.
31056222	13	7	contain	have	1927:1930	arg2	effect					1936:1941	any effect	1932:1941	any effect	1932:1941	Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome.
31056222	4	8	theme	WST-1	955:959	arg1	kit					980:982	the WST-1 cell proliferation kit	951:982	the WST-1 cell proliferation kit	951:982	Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit.
31056222	13	9	theme	membrane	1854:1861	arg1	samples					1863:1869	membrane samples	1854:1869	membrane samples prior to the placement into the cell culture	1854:1914	Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome.
31056222	2	10	theme	Human	294:298	arg1	hMSCs					324:328	hMSCs	324:328	hMSCs	324:328	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	10	theme	Human	294:298	arg1	cells					317:321	Human mesenchymal stem cells	294:321	Human mesenchymal stem cells (hMSCs)	294:329	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	10	theme	Human	294:298	arg1	PDL-hTERTs					381:390	PDL-hTERTs	381:390	PDL-hTERTs	381:390	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	1	11	theme	regenerative	190:201	arg1	procedures					203:212	oral regenerative procedures	185:212	oral regenerative procedures	185:212	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	7	12	theme	adherent	1271:1278	arg1	cells					1280:1284	adherent cells	1271:1284	adherent cells	1271:1284	The highest impact was observed for DM, its eluate doubled the cell proliferation of adherent cells when compared to the control (p<0.001).
31056222	4	13	theme	proliferation	966:978	arg1	kit					980:982	the WST-1 cell proliferation kit	951:982	the WST-1 cell proliferation kit	951:982	Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit.
31056222	2	14	dep	METHODS	286:292	arg1	hMSCs					324:328	hMSCs	324:328	hMSCs	324:328	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	14	dep	METHODS	286:292	arg1	cells					317:321	Human mesenchymal stem cells	294:321	Human mesenchymal stem cells (hMSCs)	294:329	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	14	dep	METHODS	286:292	arg1	PDL-hTERTs					381:390	PDL-hTERTs	381:390	PDL-hTERTs	381:390	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	14	dep	METHODS	286:292	arg1	cells					374:378	immortalized periodontal ligament stem cells	335:378	immortalized periodontal ligament stem cells	335:378	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	15	dep	USA	597:599	arg1	Zimmer					582:587	Zimmer	582:587	Zimmer	582:587	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	15	16	from	concentrations	2171:2184	arg1	range					2193:2197	the range	2189:2197	the range of 50-500 pg/ml	2189:2213	Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml.
31056222	15	17	theme	Growth	2064:2069	arg1	contents					2078:2085	Growth factor contents	2064:2085	Growth factor contents	2064:2085	Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml.
31056222	17	18	theme	poor	2370:2373	arg1	outcomes					2375:2382	poor outcomes	2370:2382	poor outcomes	2370:2382	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	9	19	contain	had	1418:1420	arg2	impact					1432:1437	different impact	1422:1437	different impact	1422:1437	The presence of membranes had different impact on hMSCs and PDLs.
31056222	9	19	contain	had	1418:1420	arg1	presence					1396:1403	The presence	1392:1403	The presence of membranes	1392:1416	The presence of membranes had different impact on hMSCs and PDLs.
31056222	1	20	theme	growth	235:240	arg1	content					249:255	the growth factor content	231:255	the growth factor content of these membranes in-vitro	231:283	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	13	21	from	effect	1794:1799	arg1	PDLs					1804:1807	PDLs	1804:1807	PDLs	1804:1807	Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome.
31056222	14	22	theme	OG	2027:2028	arg1	membrane					2030:2037	OG membrane	2027:2037	OG membrane	2027:2037	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	6	23	theme	hMSCs	1133:1137	arg1	proliferation					1116:1128	proliferation	1116:1128	proliferation of hMSCs	1116:1137	RESULTS The eluate of BG and BM significantly inhibited proliferation of hMSCs, whereas DM and OX showed stimulating effects.
31056222	4	24	from	days	915:918	arg1	proliferation					872:884	Cell proliferation	867:884	Cell proliferation at 3 days (eluates) and at 7 days (membranes)	867:930	Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit.
31056222	16	25	theme	higher	2255:2260	arg1	bFGF					2273:2276	bFGF	2273:2276	bFGF	2273:2276	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	16	25	theme	higher	2255:2260	arg1	amounts					2262:2268	considerably higher amounts	2242:2268	considerably higher amounts of bFGF with up to 8000 pg/ml	2242:2298	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	2	26	theme	Pharma	510:515	arg1	BG					496:497	BG	496:497	BG	496:497	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	26	theme	Pharma	510:515	arg1	AG					517:518	Geistlich Pharma AG	500:518	Geistlich Pharma AG	500:518	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	27	used	used	398:401	arg2	METHODS					286:292	METHODS	286:292	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs)	286:391	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	6	28	dep	RESULTS	1060:1066	arg1	eluate					1072:1077	The eluate	1068:1077	RESULTS The eluate of BG and BM	1060:1090	RESULTS The eluate of BG and BM significantly inhibited proliferation of hMSCs, whereas DM and OX showed stimulating effects.
31056222	0	29	theme	membranes	64:72	arg1	content					45:51	growth factor content	31:51	growth factor content	31:51	In-vitro cytocompatibility and growth factor content of GBR/GTR membranes.
31056222	0	29	theme	membranes	64:72	arg1	cytocompatibility					9:25	In-vitro cytocompatibility	0:25	In-vitro cytocompatibility	0:25	In-vitro cytocompatibility and growth factor content of GBR/GTR membranes.
31056222	13	30	theme	inhibitory	1783:1792	arg1	effect					1794:1799	no inhibitory effect	1780:1799	no inhibitory effect on PDLs	1780:1807	Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome.
31056222	1	31	theme	membranes	166:174	arg1	cytocompatibility					99:115	the cytocompatibility	95:115	the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures	95:212	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	17	32	theme	eluate	2540:2545	arg1	tests					2547:2551	eluate tests	2540:2551	eluate tests	2540:2551	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	4	33	from	days	891:894	arg1	proliferation					872:884	Cell proliferation	867:884	Cell proliferation at 3 days (eluates) and at 7 days (membranes)	867:930	Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit.
31056222	2	34	dep	collagen	477:484	arg1	Biogide					487:493	Biogide	487:493	Biogide	487:493	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	16	35	with	amounts	2262:2268	arg1	pg/ml					2294:2298	up to 8000 pg/ml	2283:2298	up to 8000 pg/ml	2283:2298	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	2	36	dep	Biogide	487:493	arg1	Switzerland					521:531	Switzerland	521:531	Switzerland	521:531	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	36	dep	Biogide	487:493	arg1	BG					496:497	BG	496:497	BG	496:497	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	36	dep	Biogide	487:493	arg1	OX					613:614	OX	613:614	OX	613:614	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	36	dep	Biogide	487:493	arg1	Dental					623:628	Datum Dental	617:628	Datum Dental	617:628	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	36	dep	Biogide	487:493	arg1	Israel					631:636	Israel	631:636	Israel	631:636	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	36	dep	Biogide	487:493	arg1	AG					517:518	Geistlich Pharma AG	500:518	Geistlich Pharma AG	500:518	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	1	37	theme	xenogenic	148:156	arg1	membranes					166:174	five commercially available xenogenic barrier membranes	120:174	five commercially available xenogenic barrier membranes used for oral regenerative procedures	120:212	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	16	38	contain	contained	2232:2240	arg1	DM					2229:2230	DM	2229:2230	DM	2229:2230	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	16	38	contain	contained	2232:2240	arg2	bFGF					2273:2276	bFGF	2273:2276	bFGF	2273:2276	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	16	38	contain	contained	2232:2240	arg2	amounts					2262:2268	considerably higher amounts	2242:2268	considerably higher amounts of bFGF with up to 8000 pg/ml	2242:2298	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	17	39	theme	ECM-membrane	2503:2514	arg1	DM					2516:2517	the ECM-membrane DM	2499:2517	the ECM-membrane DM in both membrane and eluate tests	2499:2551	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	15	40	theme	pg/ml	2209:2213	arg1	range					2193:2197	the range	2189:2197	the range of 50-500 pg/ml	2189:2213	Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml.
31056222	14	41	theme	strongest	1963:1971	arg1	inhibition					1973:1982	The strongest inhibition	1959:1982	The strongest inhibition of proliferation	1959:1999	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	0	42	theme	In-vitro	0:7	arg1	cytocompatibility					9:25	In-vitro cytocompatibility	0:25	In-vitro cytocompatibility	0:25	In-vitro cytocompatibility and growth factor content of GBR/GTR membranes.
31056222	2	43	theme	membranes	459:467	arg1	cytocompatibility					420:436	the cytocompatibility	416:436	the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing	416:747	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	18	44	dep	factors	2589:2595	arg1	differences					2609:2619	differences	2609:2619	differences observed in composition, processing and bFGF content	2609:2672	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	2	45	theme	xenogenic	441:449	arg1	membranes					459:467	xenogenic barrier membranes	441:467	xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA)	441:706	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	5	46	theme	membranes	1014:1022	arg1	content					999:1005	Growth factor content	985:1005	Growth factor content of the membranes	985:1022	Growth factor content of the membranes was measured using multiplex ELISA.
31056222	10	47	theme	BG	1519:1520	arg1	effects					1508:1514	the inhibitory effects	1493:1514	the inhibitory effects of BG, OG and BM	1493:1531	hMSCs seem to be more resistant to the inhibitory effects of BG, OG and BM.
31056222	4	48	theme	Cell	867:870	arg1	proliferation					872:884	Cell proliferation	867:884	Cell proliferation at 3 days (eluates) and at 7 days (membranes)	867:930	Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit.
31056222	0	49	theme	factor	38:43	arg1	content					45:51	growth factor content	31:51	growth factor content	31:51	In-vitro cytocompatibility and growth factor content of GBR/GTR membranes.
31056222	13	50	theme	cell	1903:1906	arg1	culture					1908:1914	the cell culture	1899:1914	the cell culture	1899:1914	Once BG is washed no inhibitory effect on PDLs was observed, however overall the washing of membrane samples prior to the placement into the cell culture did hardly have any effect on the outcome.
31056222	2	51	dep	Switzerland	521:531	arg1	USA					597:599	USA	597:599	USA	597:599	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	51	dep	Switzerland	521:531	arg1	OssixPlus					602:610	OssixPlus	602:610	OssixPlus	602:610	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	51	dep	Switzerland	521:531	arg1	USA					562:564	USA	562:564	USA	562:564	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	16	52	theme	bFGF	2273:2276	arg1	bFGF					2273:2276	bFGF	2273:2276	bFGF	2273:2276	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	16	52	theme	bFGF	2273:2276	arg1	amounts					2262:2268	considerably higher amounts	2242:2268	considerably higher amounts of bFGF with up to 8000 pg/ml	2242:2298	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	8	53	theme	cell	1368:1371	arg1	cultures					1373:1380	eluate cell cultures	1361:1380	eluate cell cultures (p>0.05)	1361:1389	The eluate of OG did not influence eluate cell cultures (p>0.05).
31056222	8	53	theme	cell	1368:1371	arg1	p>0.05					1383:1388	p>0.05	1383:1388	p>0.05	1383:1388	The eluate of OG did not influence eluate cell cultures (p>0.05).
31056222	2	54	theme	stem	369:372	arg1	cells					374:378	immortalized periodontal ligament stem cells	335:378	immortalized periodontal ligament stem cells	335:378	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	5	55	theme	factor	992:997	arg1	content					999:1005	Growth factor content	985:1005	Growth factor content of the membranes	985:1022	Growth factor content of the membranes was measured using multiplex ELISA.
31056222	18	56	theme	various	2581:2587	arg1	findings					2558:2565	The findings	2554:2565	The findings	2554:2565	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	18	56	theme	various	2581:2587	arg1	factors					2589:2595	various factors	2581:2595	various factors	2581:2595	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	14	57	from	BM	2020:2021	arg1	p<0.001					2054:2060	p<0.001	2054:2060	p<0.001	2054:2060	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	14	57	from	BM	2020:2021	arg1	PDL-hTERTs					2042:2051	PDL-hTERTs	2042:2051	PDL-hTERTs (p<0.001)	2042:2061	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	2	58	theme	periodontal	348:358	arg1	cells					374:378	immortalized periodontal ligament stem cells	335:378	immortalized periodontal ligament stem cells	335:378	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	1	59	theme	factor	242:247	arg1	content					249:255	the growth factor content	231:255	the growth factor content of these membranes in-vitro	231:283	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	9	60	theme	membranes	1408:1416	arg1	presence					1396:1403	The presence	1392:1403	The presence of membranes	1392:1416	The presence of membranes had different impact on hMSCs and PDLs.
31056222	9	61	theme	different	1422:1430	arg1	impact					1432:1437	different impact	1422:1437	different impact	1422:1437	The presence of membranes had different impact on hMSCs and PDLs.
31056222	17	62	dep	aldehydes	2355:2363	arg1	show					2365:2368	show	2365:2368	show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides	2365:2452	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	1	63	theme	membranes	266:274	arg1	content					249:255	the growth factor content	231:255	the growth factor content of these membranes in-vitro	231:283	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	2	64	theme	eluates	721:727	arg1	cytocompatibility					420:436	the cytocompatibility	416:436	the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing	416:747	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	10	65	theme	OG	1523:1524	arg1	effects					1508:1514	the inhibitory effects	1493:1514	the inhibitory effects of BG, OG and BM	1493:1531	hMSCs seem to be more resistant to the inhibitory effects of BG, OG and BM.
31056222	5	66	theme	multiplex	1043:1051	arg1	ELISA					1053:1057	multiplex ELISA	1043:1057	multiplex ELISA	1043:1057	Growth factor content of the membranes was measured using multiplex ELISA.
31056222	7	67	theme	cells	1280:1284	arg1	proliferation					1254:1266	the cell proliferation	1245:1266	the cell proliferation of adherent cells	1245:1284	The highest impact was observed for DM, its eluate doubled the cell proliferation of adherent cells when compared to the control (p<0.001).
31056222	4	68	theme	cell	961:964	arg1	kit					980:982	the WST-1 cell proliferation kit	951:982	the WST-1 cell proliferation kit	951:982	Cell proliferation at 3 days (eluates) and at 7 days (membranes) was assessed using the WST-1 cell proliferation kit.
31056222	6	69	theme	BM	1089:1090	arg1	eluate					1072:1077	The eluate	1068:1077	RESULTS The eluate of BG and BM	1060:1090	RESULTS The eluate of BG and BM significantly inhibited proliferation of hMSCs, whereas DM and OX showed stimulating effects.
31056222	2	70	theme	mesenchymal	300:310	arg1	hMSCs					324:328	hMSCs	324:328	hMSCs	324:328	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	70	theme	mesenchymal	300:310	arg1	cells					317:321	Human mesenchymal stem cells	294:321	Human mesenchymal stem cells (hMSCs)	294:329	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	70	theme	mesenchymal	300:310	arg1	PDL-hTERTs					381:390	PDL-hTERTs	381:390	PDL-hTERTs	381:390	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	1	71	theme	oral	185:188	arg1	procedures					203:212	oral regenerative procedures	185:212	oral regenerative procedures	185:212	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	6	72	theme	BG	1082:1083	arg1	eluate					1072:1077	The eluate	1068:1077	RESULTS The eluate of BG and BM	1060:1090	RESULTS The eluate of BG and BM significantly inhibited proliferation of hMSCs, whereas DM and OX showed stimulating effects.
31056222	17	73	theme	promising	2470:2478	arg1	results					2480:2486	promising results	2470:2486	promising results similar to the ECM-membrane DM in both membrane and eluate tests	2470:2551	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	6	74	theme	stimulating	1165:1175	arg1	effects					1177:1183	stimulating effects	1165:1183	stimulating effects	1165:1183	RESULTS The eluate of BG and BM significantly inhibited proliferation of hMSCs, whereas DM and OX showed stimulating effects.
31056222	10	75	theme	BM	1530:1531	arg1	effects					1508:1514	the inhibitory effects	1493:1514	the inhibitory effects of BG, OG and BM	1493:1531	hMSCs seem to be more resistant to the inhibitory effects of BG, OG and BM.
31056222	2	76	theme	Keystone	686:693	arg1	Dental					695:700	Keystone Dental	686:700	Keystone Dental	686:700	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	76	theme	Keystone	686:693	arg1	Dynamatrix					670:679	Dynamatrix	670:679	Dynamatrix	670:679	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	15	77	theme	factor	2071:2076	arg1	contents					2078:2085	Growth factor contents	2064:2085	Growth factor contents	2064:2085	Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml.
31056222	2	78	theme	extracellular	642:654	arg1	ECM					664:666	ECM	664:666	ECM	664:666	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	78	theme	extracellular	642:654	arg1	matrix					656:661	extracellular matrix	642:661	extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA)	642:706	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	18	79	theme	bFGF	2661:2664	arg1	content					2666:2672	bFGF content	2661:2672	bFGF content	2661:2672	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	1	80	theme	available	138:146	arg1	membranes					166:174	five commercially available xenogenic barrier membranes	120:174	five commercially available xenogenic barrier membranes used for oral regenerative procedures	120:212	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	7	81	theme	highest	1190:1196	arg1	impact					1198:1203	The highest impact	1186:1203	The highest impact	1186:1203	The highest impact was observed for DM, its eluate doubled the cell proliferation of adherent cells when compared to the control (p<0.001).
31056222	17	82	theme	collagen	2318:2325	arg1	membranes					2327:2335	The collagen membranes	2314:2335	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides	2301:2452	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	1	83	theme	barrier	158:164	arg1	membranes					166:174	five commercially available xenogenic barrier membranes	120:174	five commercially available xenogenic barrier membranes used for oral regenerative procedures	120:212	OBJECTIVE To assess the cytocompatibility of five commercially available xenogenic barrier membranes used for oral regenerative procedures and to determine the growth factor content of these membranes in-vitro.
31056222	15	84	with	membranes	2156:2164	arg1	concentrations					2171:2184	concentrations	2171:2184	concentrations in the range of 50-500 pg/ml	2171:2213	Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml.
31056222	2	85	theme	Geistlich	500:508	arg1	BG					496:497	BG	496:497	BG	496:497	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	85	theme	Geistlich	500:508	arg1	AG					517:518	Geistlich Pharma AG	500:518	Geistlich Pharma AG	500:518	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	16	86	dep	8000	2289:2292	arg1	to					2286:2287	to	2286:2287	to	2286:2287	Intriguingly DM contained considerably higher amounts of bFGF with up to 8000 pg/ml.
31056222	15	87	theme	tested	2149:2154	arg1	membranes					2156:2164	the tested membranes	2145:2164	the tested membranes with concentrations in the range of 50-500 pg/ml	2145:2213	Growth factor contents were quite similar quantitatively and qualitatively among the tested membranes with concentrations in the range of 50-500 pg/ml.
31056222	3	88	theme	washed	786:791	arg1	membranes					806:814	previously washed and unwashed membranes	775:814	previously washed and unwashed membranes (n=4)	775:820	Cells were cultured with previously washed and unwashed membranes (n=4) and in the medium used for washing (eluate).
31056222	3	88	theme	washed	786:791	arg1	n=4					817:819	n=4	817:819	n=4	817:819	Cells were cultured with previously washed and unwashed membranes (n=4) and in the medium used for washing (eluate).
31056222	12	89	with	culture	1713:1719	arg1	OG					1733:1734	OG	1733:1734	OG	1733:1734	PDLs however proliferate significantly less once they are placed into culture with BM and OG as well as BG-not washed.
31056222	12	89	with	culture	1713:1719	arg1	BM					1726:1727	BM	1726:1727	BM	1726:1727	PDLs however proliferate significantly less once they are placed into culture with BM and OG as well as BG-not washed.
31056222	12	89	with	culture	1713:1719	arg1	BG-not					1747:1752	BG-not	1747:1752	BG-not washed	1747:1759	PDLs however proliferate significantly less once they are placed into culture with BM and OG as well as BG-not washed.
31056222	14	90	theme	proliferation	1987:1999	arg1	inhibition					1973:1982	The strongest inhibition	1959:1982	The strongest inhibition of proliferation	1959:1999	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	17	91	dep	SIGNIFICANCE	2301:2312	arg1	membranes					2327:2335	The collagen membranes	2314:2335	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides	2301:2452	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	2	92	dep	matrix	656:661	arg1	USA					703:705	USA	703:705	USA	703:705	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	92	dep	matrix	656:661	arg1	DM					682:683	DM	682:683	DM	682:683	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	92	dep	matrix	656:661	arg1	Dental					695:700	Keystone Dental	686:700	Keystone Dental	686:700	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	92	dep	matrix	656:661	arg1	Dynamatrix					670:679	Dynamatrix	670:679	Dynamatrix	670:679	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	8	93	theme	OG	1340:1341	arg1	eluate					1330:1335	The eluate	1326:1335	The eluate of OG	1326:1341	The eluate of OG did not influence eluate cell cultures (p>0.05).
31056222	3	94	theme	unwashed	797:804	arg1	membranes					806:814	previously washed and unwashed membranes	775:814	previously washed and unwashed membranes (n=4)	775:820	Cells were cultured with previously washed and unwashed membranes (n=4) and in the medium used for washing (eluate).
31056222	3	94	theme	unwashed	797:804	arg1	n=4					817:819	n=4	817:819	n=4	817:819	Cells were cultured with previously washed and unwashed membranes (n=4) and in the medium used for washing (eluate).
31056222	17	95	theme	similar	2488:2494	arg1	results					2480:2486	promising results	2470:2486	promising results similar to the ECM-membrane DM in both membrane and eluate tests	2470:2551	SIGNIFICANCE The collagen membranes cross-linked with aldehydes show poor outcomes in PDLs while the collagen membrane cross-linked with polysaccharides generally shows promising results similar to the ECM-membrane DM in both membrane and eluate tests.
31056222	2	96	theme	Datum	617:621	arg1	BG					496:497	BG	496:497	BG	496:497	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	2	96	theme	Datum	617:621	arg1	Dental					623:628	Datum Dental	617:628	Datum Dental	617:628	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	0	97	theme	growth	31:36	arg1	content					45:51	growth factor content	31:51	growth factor content	31:51	In-vitro cytocompatibility and growth factor content of GBR/GTR membranes.
31056222	2	98	theme	barrier	451:457	arg1	membranes					459:467	xenogenic barrier membranes	441:467	xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA)	441:706	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	8	99	theme	eluate	1361:1366	arg1	cultures					1373:1380	eluate cell cultures	1361:1380	eluate cell cultures (p>0.05)	1361:1389	The eluate of OG did not influence eluate cell cultures (p>0.05).
31056222	8	99	theme	eluate	1361:1366	arg1	p>0.05					1383:1388	p>0.05	1383:1388	p>0.05	1383:1388	The eluate of OG did not influence eluate cell cultures (p>0.05).
31056222	18	100	located	observed	2621:2628	arg2	differences					2609:2619	differences	2609:2619	differences observed in composition, processing and bFGF content	2609:2672	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	18	100	located	observed	2621:2628	arg1	composition					2633:2643	composition	2633:2643	composition	2633:2643	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	18	100	located	observed	2621:2628	arg1	processing					2646:2655	processing	2646:2655	processing	2646:2655	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	18	100	located	observed	2621:2628	arg1	content					2666:2672	bFGF content	2661:2672	bFGF content	2661:2672	The findings may be due to various factors, especially differences observed in composition, processing and bFGF content.
31056222	0	101	theme	GBR/GTR	56:62	arg1	membranes					64:72	GBR/GTR membranes	56:72	GBR/GTR membranes	56:72	In-vitro cytocompatibility and growth factor content of GBR/GTR membranes.
31056222	5	102	theme	Growth	985:990	arg1	content					999:1005	Growth factor content	985:1005	Growth factor content of the membranes	985:1022	Growth factor content of the membranes was measured using multiplex ELISA.
31056222	2	103	theme	ligament	360:367	arg1	cells					374:378	immortalized periodontal ligament stem cells	335:378	immortalized periodontal ligament stem cells	335:378	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	14	104	from	membrane	2030:2037	arg1	p<0.001					2054:2060	p<0.001	2054:2060	p<0.001	2054:2060	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	14	104	from	membrane	2030:2037	arg1	PDL-hTERTs					2042:2051	PDL-hTERTs	2042:2051	PDL-hTERTs (p<0.001)	2042:2061	The strongest inhibition of proliferation was shown with the BM and OG membrane in PDL-hTERTs (p<0.001).
31056222	2	105	theme	immortalized	335:346	arg1	cells					374:378	immortalized periodontal ligament stem cells	335:378	immortalized periodontal ligament stem cells	335:378	METHODS Human mesenchymal stem cells (hMSCs) and immortalized periodontal ligament stem cells (PDL-hTERTs) were used to determine the cytocompatibility of xenogenic barrier membranes made of collagen (Biogide, BG, Geistlich Pharma AG, Switzerland; Biomend, BM, Zimmer Biomet, USA; Osseoguard OG, Zimmer Biomet, USA; OssixPlus, OX, Datum Dental, Israel) or extracellular matrix (ECM) (Dynamatrix, DM, Keystone Dental, USA) and of their eluates obtained by washing.
31056222	10	106	theme	inhibitory	1497:1506	arg1	effects					1508:1514	the inhibitory effects	1493:1514	the inhibitory effects of BG, OG and BM	1493:1531	hMSCs seem to be more resistant to the inhibitory effects of BG, OG and BM.
30995865	19	0	theme	WSHL	2362:2365	arg1	barley					2367:2372	WSHL barley	2362:2372	WSHL barley	2362:2372	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	10	1	theme	soluble	1370:1376	arg1	fraction					1378:1385	soluble fraction	1370:1385	soluble fraction	1370:1385	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	5	2	dep	arrangement	671:681	arg1	factorial					661:669	factorial	661:669	factorial	661:669	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	3	theme	feed	900:903	arg1	g/tonne					889:895	0 and 200 g/tonne	879:895	0 and 200 g/tonne of feed	879:903	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	4	dep	supplementation	862:876	arg1	g/tonne					889:895	0 and 200 g/tonne	879:895	0 and 200 g/tonne of feed	879:903	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	18	5	theme	feeding	2141:2147	arg1	value					2149:2153	a better feeding value	2132:2153	a better feeding value for NSH over WSHL	2132:2171	These data suggest that β-glucan content plays an important role in determining the digestibility of nutrients in barley for broilers, resulting in a better feeding value for NSH over WSHL.
30995865	16	6	theme	grain	1903:1907	arg1	type					1909:1912	grain type	1903:1912	grain type	1903:1912	Regardless of grain type, enzyme supplementation increased (P < 0.05) the CSID of nitrogen.
30995865	12	7	theme	enzyme	1593:1598	arg1	supplementation					1600:1614	enzyme supplementation	1593:1614	enzyme supplementation	1593:1614	A significant (P < 0.01) interaction was observed between the grain type and enzyme supplementation for AMEn.
30995865	15	8	contain	had	1780:1782	arg2	AA					1836:1837	AA	1836:1837	AA	1836:1837	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	15	8	contain	had	1780:1782	arg2	most					1828:1831	most	1828:1831	most	1828:1831	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	15	8	contain	had	1780:1782	arg1	Birds					1742:1746	Birds	1742:1746	Birds fed wheat- and WSHL-based diets	1742:1778	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	15	8	contain	had	1780:1782	arg2	CSID					1807:1810	the highest and lowest CSID	1784:1810	CSID	1807:1810	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	10	9	dep	NSH	1466:1468	arg1	%					1485:1485	17.1%	1481:1485	17.1%	1481:1485	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	10	9	dep	NSH	1466:1468	arg1	%					1495:1495	13.3%	1491:1495	13.3%	1491:1495	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	5	10	used	used	701:704	arg2	arrangement					671:681	A 3 × 2 factorial arrangement	653:681	A 3 × 2 factorial arrangement of treatments	653:695	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	19	11	theme	broiler	2275:2281	arg1	diets					2283:2287	broiler diets	2275:2287	broiler diets	2275:2287	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	5	12	theme	supplementation	862:876	arg1	levels					845:850	two levels	841:850	two levels of enzyme supplementation (0 and 200 g/tonne of feed)	841:904	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	12	theme	supplementation	862:876	arg1	grains					746:751	grains	746:751	grains	746:751	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	12	theme	supplementation	862:876	arg1	[NSH					782:785	normal starch hulled barley [NSH	754:785	normal starch hulled barley [NSH	754:785	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	12	theme	supplementation	862:876	arg1	wheat					830:834	wheat	830:834	wheat	830:834	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	19	13	theme	barley	2265:2270	arg1	value					2256:2260	the feeding value	2244:2260	the feeding value of barley in broiler diets	2244:2287	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	4	14	theme	barley	515:520	arg1	cultivars					522:530	two barley cultivars	511:530	two barley cultivars for broilers in comparison to wheat	511:566	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	0	15	theme	metabolisable	109:121	arg1	energy					123:128	metabolisable energy	109:128	metabolisable energy	109:128	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	13	16	theme	greatest	1685:1692	arg1	response					1694:1701	the greatest response	1681:1701	the greatest response to enzyme supplementation for AMEn	1681:1736	The WSHL, with the highest content of β-glucan, showed the greatest response to enzyme supplementation for AMEn.
30995865	6	17	contain	contained	933:941	arg2	128					951:953	128	951:953	128	951:953	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	17	contain	contained	933:941	arg2	endo-1					958:963	endo-1	958:963	endo-1	958:963	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	17	contain	contained	933:941	arg1	Enzyme					907:912	Enzyme	907:912	Enzyme supplemented diets	907:931	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	17	contain	contained	933:941	arg2	406					943:945	406	943:945	406	943:945	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	17	contain	contained	933:941	arg2	4-β-xylanase					966:977	4-β-xylanase	966:977	4-β-xylanase	966:977	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	17	contain	contained	933:941	arg2	units					1009:1013	3 (4)-β-glucanase units	991:1013	3 (4)-β-glucanase units	991:1013	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	17	contain	contained	933:941	arg2	endo-1					983:988	endo-1	983:988	endo-1	983:988	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	4	18	from	d	470:470	arg1	broilers					458:465	2; 336 Ross 308 male broilers	437:465	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.	437:651	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	3	19	with	cages	324:328	arg1	birds					341:345	eight birds	335:345	eight birds each	335:350	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	18	20	theme	nutrients	2085:2093	arg1	digestibility					2068:2080	the digestibility	2064:2080	the digestibility of nutrients in barley for broilers	2064:2116	These data suggest that β-glucan content plays an important role in determining the digestibility of nutrients in barley for broilers, resulting in a better feeding value for NSH over WSHL.
30995865	0	21	theme	amino	147:151	arg1	digestibility					158:170	standardised amino acid digestibility	134:170	standardised amino acid digestibility	134:170	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	13	22	theme	β-glucan	1664:1671	arg1	content					1653:1659	the highest content	1641:1659	the highest content of β-glucan	1641:1671	The WSHL, with the highest content of β-glucan, showed the greatest response to enzyme supplementation for AMEn.
30995865	5	23	theme	barley	775:780	arg1	grains					746:751	grains	746:751	grains	746:751	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	23	theme	barley	775:780	arg1	[NSH					782:785	normal starch hulled barley [NSH	754:785	normal starch hulled barley [NSH	754:785	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	4	24	theme	non-starch	603:612	arg1	NSP					630:632	NSP	630:632	NSP	630:632	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	4	24	theme	non-starch	603:612	arg1	polysaccharide					614:627	a multi-component non-starch polysaccharide	585:627	a multi-component non-starch polysaccharide (NSP) degrading enzyme	585:650	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	3	25	from	d	315:315	arg1	broilers					303:310	288 Ross 308 male broilers	285:310	288 Ross 308 male broilers at d 14; 36 cages with eight birds each	285:350	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	2	26	theme	AMEn	271:274	arg1	Exp					277:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	Two experiments were conducted to assess the nitrogen-corrected apparent metabolisable energy (AMEn; Exp.
30995865	8	27	theme	starch	1073:1078	arg1	higher					1092:1097	higher	1092:1097	higher	1092:1097	Analysis showed that the starch content was higher in NSH (610 g/kg) than in wheat (537 g/kg) and WSHL (554 g/kg), and the composition of starch differed markedly among the grain types.
30995865	8	27	theme	starch	1073:1078	arg1	content					1080:1086	the starch content	1069:1086	the starch content	1069:1086	Analysis showed that the starch content was higher in NSH (610 g/kg) than in wheat (537 g/kg) and WSHL (554 g/kg), and the composition of starch differed markedly among the grain types.
30995865	4	28	dep	broilers	458:465	arg1	cages					479:483	42 cages	476:483	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.	437:651	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	2	29	theme	energy	263:268	arg1	Exp					277:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	Two experiments were conducted to assess the nitrogen-corrected apparent metabolisable energy (AMEn; Exp.
30995865	0	30	theme	carbohydrase	65:76	arg1	supplementation					78:92	carbohydrase supplementation	65:92	carbohydrase supplementation	65:92	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	5	31	theme	starch	761:766	arg1	grains					746:751	grains	746:751	grains	746:751	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	31	theme	starch	761:766	arg1	[NSH					782:785	normal starch hulled barley [NSH	754:785	normal starch hulled barley [NSH	754:785	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	18	32	theme	β-glucan	2008:2015	arg1	content					2017:2023	β-glucan content	2008:2023	β-glucan content	2008:2023	These data suggest that β-glucan content plays an important role in determining the digestibility of nutrients in barley for broilers, resulting in a better feeding value for NSH over WSHL.
30995865	19	33	from	pronounced	2348:2357	arg1	barley					2367:2372	WSHL barley	2362:2372	WSHL barley	2362:2372	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	19	34	theme	NSP-degrading	2211:2223	arg1	enzyme					2225:2230	a multi-component NSP-degrading enzyme	2193:2230	a multi-component NSP-degrading enzyme	2193:2230	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	8	35	theme	grain	1221:1225	arg1	types					1227:1231	the grain types	1217:1231	the grain types	1217:1231	Analysis showed that the starch content was higher in NSH (610 g/kg) than in wheat (537 g/kg) and WSHL (554 g/kg), and the composition of starch differed markedly among the grain types.
30995865	0	36	theme	cultivars	37:45	arg1	evaluation					12:21	Nutritional evaluation	0:21	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.	0:171	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	18	37	theme	important	2034:2042	arg1	role					2044:2047	an important role	2031:2047	an important role	2031:2047	These data suggest that β-glucan content plays an important role in determining the digestibility of nutrients in barley for broilers, resulting in a better feeding value for NSH over WSHL.
30995865	19	38	from	value	2256:2260	arg1	diets					2283:2287	broiler diets	2275:2287	broiler diets	2275:2287	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	3	39	theme	ileal	385:389	arg1	CSID					406:409	CSID	406:409	CSID	406:409	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	3	39	theme	ileal	385:389	arg1	digestibility					391:403	standardised ileal digestibility	372:403	standardised ileal digestibility (CSID) of amino acids (AA	372:429	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	0	40	theme	Nutritional	0:10	arg1	evaluation					12:21	Nutritional evaluation	0:21	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.	0:171	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	5	41	theme	waxy	789:792	arg1	[WSHL					818:822	waxy starch hull-less barley [WSHL	789:822	waxy starch hull-less barley [WSHL	789:822	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	3	42	dep	broilers	303:310	arg1	cages					324:328	36 cages	321:328	288 Ross 308 male broilers at d 14; 36 cages with eight birds each	285:350	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	5	43	dep	grains	746:751	arg1	[WSHL					818:822	waxy starch hull-less barley [WSHL	789:822	waxy starch hull-less barley [WSHL	789:822	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	3	44	theme	amino	415:419	arg1	acids					421:425	amino acids	415:425	amino acids (AA	415:429	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	5	45	theme	hull-less	801:809	arg1	[WSHL					818:822	waxy starch hull-less barley [WSHL	789:822	waxy starch hull-less barley [WSHL	789:822	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	15	46	theme	WSHL-based	1763:1772	arg1	diets					1774:1778	wheat- and WSHL-based diets	1752:1778	wheat- and WSHL-based diets	1752:1778	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	12	47	dep	type	1584:1587	arg1	the					1574:1576	the	1574:1576	the	1574:1576	A significant (P < 0.01) interaction was observed between the grain type and enzyme supplementation for AMEn.
30995865	0	48	theme	barley	30:35	arg1	cultivars					37:45	two barley cultivars	26:45	two barley cultivars	26:45	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	5	49	theme	levels	845:850	arg1	types					737:741	three types	731:741	three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed)	731:904	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	4	50	theme	Ross	444:447	arg1	broilers					458:465	2; 336 Ross 308 male broilers	437:465	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.	437:651	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	15	51	theme	lowest	1800:1805	arg1	CSID					1807:1810	the highest and lowest CSID	1784:1810	CSID	1807:1810	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	5	52	theme	enzyme	855:860	arg1	supplementation					862:876	enzyme supplementation	855:876	enzyme supplementation (0 and 200 g/tonne of feed)	855:904	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	4	53	theme	male	453:456	arg1	broilers					458:465	2; 336 Ross 308 male broilers	437:465	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.	437:651	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	16	54	theme	P	1949:1949	arg1	<					1951:1951	P < 0.05	1949:1956	P < 0.05	1949:1956	Regardless of grain type, enzyme supplementation increased (P < 0.05) the CSID of nitrogen.
30995865	10	55	theme	total	1394:1398	arg1	polysaccharides					1411:1425	the total non-starch polysaccharides	1390:1425	the total non-starch polysaccharides	1390:1425	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	5	56	theme	wheat	830:834	arg1	types					737:741	three types	731:741	three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed)	731:904	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	15	57	theme	NSH	1859:1861	arg1	diets					1863:1867	NSH diets	1859:1867	NSH diets	1859:1867	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	16	58	theme	nitrogen	1971:1978	arg1	CSID					1963:1966	the CSID	1959:1966	the CSID of nitrogen	1959:1978	Regardless of grain type, enzyme supplementation increased (P < 0.05) the CSID of nitrogen.
30995865	3	59	dep	acids	421:425	arg1	AA					428:429	AA	428:429	AA	428:429	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	3	60	dep	1	282:282	arg1	broilers					303:310	288 Ross 308 male broilers	285:310	288 Ross 308 male broilers at d 14; 36 cages with eight birds each	285:350	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	3	60	dep	1	282:282	arg1	Exp					432:434	Exp	432:434	Exp	432:434	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	10	61	theme	fraction	1378:1385	arg1	contribution					1354:1365	The contribution	1350:1365	The contribution of soluble fraction to the total non-starch polysaccharides	1350:1425	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	10	61	theme	fraction	1378:1385	arg1	higher					1431:1436	higher	1431:1436	higher	1431:1436	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	12	62	theme	grain	1578:1582	arg1	type					1584:1587	grain type	1578:1587	grain type	1578:1587	A significant (P < 0.01) interaction was observed between the grain type and enzyme supplementation for AMEn.
30995865	6	63	theme	endo-1	983:988	arg1	endo-1					958:963	endo-1	958:963	endo-1	958:963	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	63	theme	endo-1	983:988	arg1	endo-1					983:988	endo-1	983:988	endo-1	983:988	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	63	theme	endo-1	983:988	arg1	406					943:945	406	943:945	406	943:945	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	63	theme	endo-1	983:988	arg1	4-β-xylanase					966:977	4-β-xylanase	966:977	4-β-xylanase	966:977	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	63	theme	endo-1	983:988	arg1	units					1009:1013	3 (4)-β-glucanase units	991:1013	3 (4)-β-glucanase units	991:1013	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	18	64	theme	better	2134:2139	arg1	value					2149:2153	a better feeding value	2132:2153	a better feeding value for NSH over WSHL	2132:2171	These data suggest that β-glucan content plays an important role in determining the digestibility of nutrients in barley for broilers, resulting in a better feeding value for NSH over WSHL.
30995865	10	65	theme	non-starch	1400:1409	arg1	polysaccharides					1411:1425	the total non-starch polysaccharides	1390:1425	the total non-starch polysaccharides	1390:1425	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	5	66	dep	factorial	661:669	arg1	×					657:657	×	657:657	×	657:657	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	6	67	theme	4-β-xylanase	966:977	arg1	endo-1					958:963	endo-1	958:963	endo-1	958:963	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	67	theme	4-β-xylanase	966:977	arg1	endo-1					983:988	endo-1	983:988	endo-1	983:988	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	67	theme	4-β-xylanase	966:977	arg1	406					943:945	406	943:945	406	943:945	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	67	theme	4-β-xylanase	966:977	arg1	4-β-xylanase					966:977	4-β-xylanase	966:977	4-β-xylanase	966:977	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	67	theme	4-β-xylanase	966:977	arg1	units					1009:1013	3 (4)-β-glucanase units	991:1013	3 (4)-β-glucanase units	991:1013	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	68	theme	feed	1025:1028	arg1	kg					1019:1020	kg	1019:1020	kg of feed	1019:1028	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	4	69	from	broilers	536:543	arg1	comparison					548:557	comparison	548:557	comparison to wheat	548:566	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	6	70	theme	endo-1	958:963	arg1	endo-1					958:963	endo-1	958:963	endo-1	958:963	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	70	theme	endo-1	958:963	arg1	endo-1					983:988	endo-1	983:988	endo-1	983:988	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	70	theme	endo-1	958:963	arg1	406					943:945	406	943:945	406	943:945	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	70	theme	endo-1	958:963	arg1	4-β-xylanase					966:977	4-β-xylanase	966:977	4-β-xylanase	966:977	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	70	theme	endo-1	958:963	arg1	units					1009:1013	3 (4)-β-glucanase units	991:1013	3 (4)-β-glucanase units	991:1013	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	16	71	theme	enzyme	1915:1920	arg1	supplementation					1922:1936	enzyme supplementation	1915:1936	enzyme supplementation	1915:1936	Regardless of grain type, enzyme supplementation increased (P < 0.05) the CSID of nitrogen.
30995865	0	72	theme	standardised	134:145	arg1	digestibility					158:170	standardised amino acid digestibility	134:170	standardised amino acid digestibility	134:170	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	2	73	theme	metabolisable	249:261	arg1	Exp					277:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	Two experiments were conducted to assess the nitrogen-corrected apparent metabolisable energy (AMEn; Exp.
30995865	12	74	theme	<	1533:1533	arg1	P					1531:1531	P < 0.01	1531:1538	P < 0.01	1531:1538	A significant (P < 0.01) interaction was observed between the grain type and enzyme supplementation for AMEn.
30995865	4	75	theme	cultivars	522:530	arg1	birds					496:500	eight birds	490:500	eight birds each) of two barley cultivars for broilers in comparison to wheat	490:566	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	12	76	dep	significant	1518:1528	arg1	P					1531:1531	P < 0.01	1531:1538	P < 0.01	1531:1538	A significant (P < 0.01) interaction was observed between the grain type and enzyme supplementation for AMEn.
30995865	0	77	theme	acid	153:156	arg1	digestibility					158:170	standardised amino acid digestibility	134:170	standardised amino acid digestibility	134:170	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	13	78	theme	enzyme	1706:1711	arg1	supplementation					1713:1727	enzyme supplementation	1706:1727	enzyme supplementation	1706:1727	The WSHL, with the highest content of β-glucan, showed the greatest response to enzyme supplementation for AMEn.
30995865	2	79	theme	nitrogen-corrected	221:238	arg1	Exp					277:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	Two experiments were conducted to assess the nitrogen-corrected apparent metabolisable energy (AMEn; Exp.
30995865	5	80	theme	hulled	768:773	arg1	grains					746:751	grains	746:751	grains	746:751	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	80	theme	hulled	768:773	arg1	[NSH					782:785	normal starch hulled barley [NSH	754:785	normal starch hulled barley [NSH	754:785	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	3	81	theme	male	298:301	arg1	broilers					303:310	288 Ross 308 male broilers	285:310	288 Ross 308 male broilers at d 14; 36 cages with eight birds each	285:350	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	6	82	theme	-β-glucanase	996:1007	arg1	endo-1					958:963	endo-1	958:963	endo-1	958:963	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	82	theme	-β-glucanase	996:1007	arg1	units					1009:1013	3 (4)-β-glucanase units	991:1013	3 (4)-β-glucanase units	991:1013	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	82	theme	-β-glucanase	996:1007	arg1	406					943:945	406	943:945	406	943:945	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	82	theme	-β-glucanase	996:1007	arg1	4-β-xylanase					966:977	4-β-xylanase	966:977	4-β-xylanase	966:977	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	6	82	theme	-β-glucanase	996:1007	arg1	endo-1					983:988	endo-1	983:988	endo-1	983:988	Enzyme supplemented diets contained 406 and 128 of endo-1, 4-β-xylanase and endo-1, 3 (4)-β-glucanase units per kg of feed, respectively.
30995865	10	83	dep	higher	1431:1436	arg1	%					1451:1451	38.2%	1447:1451	38.2%	1447:1451	The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively).
30995865	19	84	from	barley	2367:2372	arg1	effect					2330:2335	the effect	2326:2335	the effect	2326:2335	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	19	84	from	barley	2367:2372	arg1	pronounced					2348:2357	pronounced	2348:2357	pronounced	2348:2357	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	3	85	theme	Ross	289:292	arg1	broilers					303:310	288 Ross 308 male broilers	285:310	288 Ross 308 male broilers at d 14; 36 cages with eight birds each	285:350	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	8	86	theme	starch	1186:1191	arg1	composition					1171:1181	the composition	1167:1181	the composition of starch	1167:1191	Analysis showed that the starch content was higher in NSH (610 g/kg) than in wheat (537 g/kg) and WSHL (554 g/kg), and the composition of starch differed markedly among the grain types.
30995865	9	87	theme	β-glucan	1238:1245	arg1	content					1247:1253	The β-glucan content	1234:1253	The β-glucan content	1234:1253	The β-glucan content was considerably higher in WSHL (68.6 g/kg) compared to NSH (38.5 g/kg) and wheat (7.74 g/kg).
30995865	9	87	theme	β-glucan	1238:1245	arg1	higher					1272:1277	higher	1272:1277	higher	1272:1277	The β-glucan content was considerably higher in WSHL (68.6 g/kg) compared to NSH (38.5 g/kg) and wheat (7.74 g/kg).
30995865	4	88	theme	multi-component	587:601	arg1	NSP					630:632	NSP	630:632	NSP	630:632	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	4	88	theme	multi-component	587:601	arg1	polysaccharide					614:627	a multi-component non-starch polysaccharide	585:627	a multi-component non-starch polysaccharide (NSP) degrading enzyme	585:650	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	4	89	dep	birds	496:500	arg1	each					502:505	each	502:505	each	502:505	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	4	90	with	cages	479:483	arg1	NSP					630:632	NSP	630:632	NSP	630:632	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	4	90	with	cages	479:483	arg1	polysaccharide					614:627	a multi-component non-starch polysaccharide	585:627	a multi-component non-starch polysaccharide (NSP) degrading enzyme	585:650	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	4	90	with	cages	479:483	arg1	birds					496:500	eight birds	490:500	eight birds each) of two barley cultivars for broilers in comparison to wheat	490:566	2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme.
30995865	5	91	theme	grains	746:751	arg1	types					737:741	three types	731:741	three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed)	731:904	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	13	92	with	WSHL	1630:1633	arg1	content					1653:1659	the highest content	1641:1659	the highest content of β-glucan	1641:1671	The WSHL, with the highest content of β-glucan, showed the greatest response to enzyme supplementation for AMEn.
30995865	13	93	theme	highest	1645:1651	arg1	content					1653:1659	the highest content	1641:1659	the highest content of β-glucan	1641:1671	The WSHL, with the highest content of β-glucan, showed the greatest response to enzyme supplementation for AMEn.
30995865	12	94	theme	significant	1518:1528	arg1	interaction					1541:1551	A significant (P < 0.01) interaction	1516:1551	A significant (P < 0.01) interaction	1516:1551	A significant (P < 0.01) interaction was observed between the grain type and enzyme supplementation for AMEn.
30995865	16	95	dep	increased	1938:1946	arg1	<					1951:1951	P < 0.05	1949:1956	P < 0.05	1949:1956	Regardless of grain type, enzyme supplementation increased (P < 0.05) the CSID of nitrogen.
30995865	5	96	theme	normal	754:759	arg1	grains					746:751	grains	746:751	grains	746:751	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	96	theme	normal	754:759	arg1	[NSH					782:785	normal starch hulled barley [NSH	754:785	normal starch hulled barley [NSH	754:785	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	3	97	dep	birds	341:345	arg1	each					347:350	each	347:350	each	347:350	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	15	98	theme	wheat-	1752:1757	arg1	diets					1774:1778	wheat- and WSHL-based diets	1752:1778	wheat- and WSHL-based diets	1752:1778	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	18	99	from	digestibility	2068:2080	arg1	barley					2098:2103	barley	2098:2103	barley for broilers	2098:2116	These data suggest that β-glucan content plays an important role in determining the digestibility of nutrients in barley for broilers, resulting in a better feeding value for NSH over WSHL.
30995865	5	100	theme	barley	811:816	arg1	[WSHL					818:822	waxy starch hull-less barley [WSHL	789:822	waxy starch hull-less barley [WSHL	789:822	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	3	101	theme	digestibility	391:403	arg1	coefficient					357:367	coefficient	357:367	coefficient of standardised ileal digestibility (CSID) of amino acids (AA	357:429	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	5	102	theme	treatments	686:695	arg1	arrangement					671:681	A 3 × 2 factorial arrangement	653:681	A 3 × 2 factorial arrangement of treatments	653:695	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	103	theme	starch	794:799	arg1	[WSHL					818:822	waxy starch hull-less barley [WSHL	789:822	waxy starch hull-less barley [WSHL	789:822	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	5	104	with	experiments	714:724	arg1	types					737:741	three types	731:741	three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed)	731:904	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	3	105	theme	acids	421:425	arg1	CSID					406:409	CSID	406:409	CSID	406:409	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	3	105	theme	acids	421:425	arg1	digestibility					391:403	standardised ileal digestibility	372:403	standardised ileal digestibility (CSID) of amino acids (AA	372:429	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	5	106	theme	3	655:655	arg1	×					657:657	×	657:657	×	657:657	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	19	107	theme	enzyme	2225:2230	arg1	Supplementation					2174:2188	Supplementation	2174:2188	Supplementation of a multi-component NSP-degrading enzyme	2174:2230	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	3	108	theme	standardised	372:383	arg1	CSID					406:409	CSID	406:409	CSID	406:409	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	3	108	theme	standardised	372:383	arg1	digestibility					391:403	standardised ileal digestibility	372:403	standardised ileal digestibility (CSID) of amino acids (AA	372:429	1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp.
30995865	5	109	theme	2	659:659	arg1	×					657:657	×	657:657	×	657:657	A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed).
30995865	15	110	theme	nitrogen	1815:1822	arg1	CSID					1807:1810	the highest and lowest CSID	1784:1810	CSID	1807:1810	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	19	111	theme	multi-component	2195:2209	arg1	enzyme					2225:2230	a multi-component NSP-degrading enzyme	2193:2230	a multi-component NSP-degrading enzyme	2193:2230	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	19	112	theme	feeding	2248:2254	arg1	value					2256:2260	the feeding value	2244:2260	the feeding value of barley in broiler diets	2244:2287	Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.
30995865	2	113	theme	apparent	240:247	arg1	Exp					277:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	the nitrogen-corrected apparent metabolisable energy (AMEn; Exp	217:279	Two experiments were conducted to assess the nitrogen-corrected apparent metabolisable energy (AMEn; Exp.
30995865	15	114	theme	highest	1788:1794	arg1	CSID					1807:1810	the highest and lowest CSID	1784:1810	CSID	1807:1810	Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate.
30995865	0	115	dep	evaluation	12:21	arg1	digestibility					158:170	standardised amino acid digestibility	134:170	standardised amino acid digestibility	134:170	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30995865	0	115	dep	evaluation	12:21	arg1	energy					123:128	metabolisable energy	109:128	metabolisable energy	109:128	Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.
30552185	9	0	theme	periodontal	2195:2205	arg1	disease					2207:2213	periodontal disease	2195:2213	periodontal disease	2195:2213	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	3	1	theme	gingivalis	709:718	arg1	physiology					692:701	physiology	692:701	physiology	692:701	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	3	1	theme	gingivalis	709:718	arg1	growth					681:686	growth	681:686	growth	681:686	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	9	2	theme	increased	2216:2224	arg1	fluctuations					2378:2389	known ecological fluctuations	2361:2389	known ecological fluctuations prominently associated with progression toward disease	2361:2444	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	2	theme	increased	2216:2224	arg1	accumulation					2279:2290	the accumulation	2275:2290	the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci	2275:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	2	theme	increased	2216:2224	arg1	pH					2232:2233	increased local pH	2216:2233	increased local pH	2216:2233	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	2	theme	increased	2216:2224	arg1	shift					2238:2242	a shift	2236:2242	a shift to anaerobic surroundings	2236:2268	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	8	3	theme	gingivalis	1934:1943	arg1	physiology					1917:1926	the physiology	1913:1926	the physiology of P. gingivalis	1913:1943	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	11	4	dep	increase	2792:2799	arg1	affect					2838:2843	affect	2838:2843	affect the physiological state of the subgingival microbiota	2838:2897	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	4	5	theme	cells	1166:1170	arg1	expansion					1142:1150	the expansion	1138:1150	the expansion of individual cells which contained large intracellular granules	1138:1215	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	11	6	theme	physiological	2849:2861	arg1	state					2863:2867	the physiological state	2845:2867	the physiological state of the subgingival microbiota	2845:2897	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	9	7	theme	disease	2207:2213	arg1	case					2187:2190	the case	2183:2190	the case of periodontal disease	2183:2213	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	2	8	theme	diverse	350:356	arg1	array					358:362	a diverse array	348:362	a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds	348:434	Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and P. gingivalis produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core.
30552185	11	9	theme	subgingival	2876:2886	arg1	microbiota					2888:2897	the subgingival microbiota	2872:2897	the subgingival microbiota	2872:2897	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	12	10	theme	monosaccharides	2946:2960	arg1	impact					2931:2936	the impact	2927:2936	the impact of free monosaccharides on P. gingivalis	2927:2977	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	3	11	theme	monosaccharides	604:618	arg1	effect					583:588	the effect	579:588	the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested	579:746	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	9	12	theme	known	2361:2365	arg1	fluctuations					2378:2389	known ecological fluctuations	2361:2389	known ecological fluctuations prominently associated with progression toward disease	2361:2444	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	12	theme	known	2361:2365	arg1	accumulation					2279:2290	the accumulation	2275:2290	the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci	2275:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	12	theme	known	2361:2365	arg1	pH					2232:2233	increased local pH	2216:2233	increased local pH	2216:2233	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	12	theme	known	2361:2365	arg1	shift					2238:2242	a shift	2236:2242	a shift to anaerobic surroundings	2236:2268	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	3	13	theme	bacterial	802:810	arg1	culture					812:818	the bacterial culture	798:818	the bacterial culture	798:818	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	10	14	theme	food	2504:2507	arg1	webs					2509:2512	subgingival food webs	2492:2512	subgingival food webs	2492:2512	Importantly, in contrast, the alterations to subgingival food webs in disease sites remain poorly characterized.
30552185	1	15	theme	anaerobe	140:147	arg1	gingivalis					163:172	The asaccharolytic anaerobe Porphyromonas gingivalis	121:172	The asaccharolytic anaerobe Porphyromonas gingivalis	121:172	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	4	16	theme	electron	949:956	arg1	micrographs					958:968	electron micrographs	949:968	electron micrographs	949:968	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	8	17	theme	Environmental	2029:2041	arg1	perturbations					2043:2055	large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations	1967:2055	large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations	1967:2055	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	12	18	theme	periodontal	3079:3089	arg1	pathogen					3091:3098	this periodontal pathogen	3074:3098	this periodontal pathogen	3074:3098	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	7	19	theme	exponential	1669:1679	arg1	phase					1681:1685	late exponential phase	1664:1685	late exponential phase	1664:1685	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	8	20	dep	large	1967:1971	arg1	undefined					1984:1992	undefined	1984:1992	undefined	1984:1992	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	8	20	dep	large	1967:1971	arg1	intracellular					1995:2007	intracellular	1995:2007	intracellular	1995:2007	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	4	21	theme	intracellular	1194:1206	arg1	granules					1208:1215	large intracellular granules	1188:1215	large intracellular granules	1188:1215	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	9	22	theme	Gram-negative	2295:2307	arg1	anaerobes					2309:2317	Gram-negative anaerobes	2295:2317	Gram-negative anaerobes	2295:2317	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	6	23	theme	enzyme-linked	1446:1458	arg1	ELISA					1481:1485	ELISA	1481:1485	ELISA	1481:1485	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	6	23	theme	enzyme-linked	1446:1458	arg1	assay					1474:1478	an enzyme-linked immunosorbent assay	1443:1478	an enzyme-linked immunosorbent assay (ELISA)	1443:1486	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	4	24	theme	cell	1080:1083	arg1	numbers					1085:1091	cell numbers	1080:1091	cell numbers	1080:1091	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	3	25	theme	stationary	918:927	arg1	phase					929:933	stationary phase	918:933	stationary phase	918:933	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	8	26	dep	production	1953:1962	arg1	central					2061:2067	central	2061:2067	central	2061:2067	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	1	27	link	host-derived	246:257	arg1	mucins					281:286	mucins	281:286	mucins	281:286	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	1	27	link	host-derived	246:257	arg1	immunoglobulins					292:306	immunoglobulins	292:306	immunoglobulins	292:306	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	1	27	link	host-derived	246:257	arg1	glycoproteins					259:271	host-derived glycoproteins	246:271	host-derived glycoproteins such as mucins and immunoglobulins	246:306	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	5	28	from	increase	1289:1296	arg1	carbohydrates					1309:1321	soluble carbohydrates	1301:1321	soluble carbohydrates	1301:1321	Initial attempts to characterize these granules revealed only a subtle increase in soluble carbohydrates, suggesting they are likely not composed of stored carbohydrate.
30552185	0	29	theme	Oral	79:82	arg1	gingivalis					109:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	8	30	theme	host	1877:1880	arg1	proteins					1882:1889	host proteins	1877:1889	host proteins	1877:1889	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	4	31	theme	gingivalis	988:997	arg1	plating					974:980	plating	974:980	plating of P. gingivalis in stationary phase	974:1017	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	4	31	theme	gingivalis	988:997	arg1	micrographs					958:968	electron micrographs	949:968	electron micrographs	949:968	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	0	32	theme	Porphyromonas	95:107	arg1	gingivalis					109:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	11	33	from	glycoproteins	2773:2785	arg1	cleavage					2759:2766	cleavage	2759:2766	cleavage from glycoproteins	2759:2785	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	7	34	theme	changes	1631:1637	arg1	investigation					1594:1606	an initial investigation	1583:1606	an initial investigation of the transcriptional changes elicited by galactose in late exponential phase	1583:1685	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	4	35	theme	stationary	1002:1011	arg1	phase					1013:1017	stationary phase	1002:1017	stationary phase	1002:1017	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	5	36	dep	Initial	1218:1224	arg1	attempts					1226:1233	attempts	1226:1233	attempts to characterize these granules	1226:1264	Initial attempts to characterize these granules revealed only a subtle increase in soluble carbohydrates, suggesting they are likely not composed of stored carbohydrate.
30552185	6	37	link	enzyme-linked	1446:1458	arg1	ELISA					1481:1485	ELISA	1481:1485	ELISA	1481:1485	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	6	37	link	enzyme-linked	1446:1458	arg1	assay					1474:1478	an enzyme-linked immunosorbent assay	1443:1478	an enzyme-linked immunosorbent assay (ELISA)	1443:1486	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	9	38	theme	Gram-positive	2337:2349	arg1	cocci					2351:2355	Gram-positive cocci	2337:2355	Gram-positive cocci	2337:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	8	39	theme	pathobionts	2087:2097	arg1	ability					2076:2082	the ability	2072:2082	the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites	2072:2177	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	12	40	theme	P.	2965:2966	arg1	gingivalis					2968:2977	P. gingivalis	2965:2977	P. gingivalis	2965:2977	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	7	41	theme	stress	1753:1758	arg1	response					1760:1767	the general stress response	1741:1767	the general stress response	1741:1767	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	0	42	theme	Asaccharolytic	64:77	arg1	gingivalis					109:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	1	43	dep	it	195:196	arg1	encounters					198:207	encounters	198:207	encounters in the periodontal pocket	198:233	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	8	44	theme	diseased	2164:2171	arg1	sites					2173:2177	diseased sites	2164:2177	diseased sites	2164:2177	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	10	45	theme	disease	2517:2523	arg1	sites					2525:2529	disease sites	2517:2529	disease sites	2517:2529	Importantly, in contrast, the alterations to subgingival food webs in disease sites remain poorly characterized.
30552185	5	46	theme	stored	1367:1372	arg1	carbohydrate					1374:1385	stored carbohydrate	1367:1385	stored carbohydrate	1367:1385	Initial attempts to characterize these granules revealed only a subtle increase in soluble carbohydrates, suggesting they are likely not composed of stored carbohydrate.
30552185	9	47	theme	ecological	2367:2376	arg1	fluctuations					2378:2389	known ecological fluctuations	2361:2389	known ecological fluctuations prominently associated with progression toward disease	2361:2444	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	47	theme	ecological	2367:2376	arg1	accumulation					2279:2290	the accumulation	2275:2290	the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci	2275:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	47	theme	ecological	2367:2376	arg1	pH					2232:2233	increased local pH	2216:2233	increased local pH	2216:2233	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	47	theme	ecological	2367:2376	arg1	shift					2238:2242	a shift	2236:2242	a shift to anaerobic surroundings	2236:2268	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	8	48	theme	Porphyromonas	2108:2120	arg1	gingivalis					2122:2131	Porphyromonas gingivalis	2108:2131	Porphyromonas gingivalis	2108:2131	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	7	49	theme	initial	1586:1592	arg1	investigation					1594:1606	an initial investigation	1583:1606	an initial investigation of the transcriptional changes elicited by galactose in late exponential phase	1583:1685	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	3	50	theme	P.	706:707	arg1	gingivalis					709:718	P. gingivalis	706:718	P. gingivalis	706:718	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	2	51	theme	carbohydrates	367:379	arg1	array					358:362	a diverse array	348:362	a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds	348:434	Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and P. gingivalis produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core.
30552185	5	52	theme	subtle	1282:1287	arg1	increase					1289:1296	only a subtle increase	1275:1296	only a subtle increase in soluble carbohydrates	1275:1321	Initial attempts to characterize these granules revealed only a subtle increase in soluble carbohydrates, suggesting they are likely not composed of stored carbohydrate.
30552185	10	53	theme	subgingival	2492:2502	arg1	webs					2509:2512	subgingival food webs	2492:2512	subgingival food webs	2492:2512	Importantly, in contrast, the alterations to subgingival food webs in disease sites remain poorly characterized.
30552185	12	54	theme	deeper	2987:2992	arg1	insight					2994:3000	deeper insight	2987:3000	deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen	2987:3098	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	3	55	theme	carbohydrates	727:739	arg1	physiology					692:701	physiology	692:701	physiology	692:701	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	3	55	theme	carbohydrates	727:739	arg1	growth					681:686	growth	681:686	growth	681:686	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	8	56	theme	P.	1931:1932	arg1	gingivalis					1934:1943	P. gingivalis	1931:1943	P. gingivalis	1931:1943	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	2	57	theme	polypeptide	397:407	arg1	chain					409:413	the polypeptide chain	393:413	the polypeptide chain	393:413	Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and P. gingivalis produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core.
30552185	1	58	gly	glycoproteins	259:271	arg1	mucins					281:286	mucins	281:286	mucins	281:286	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	1	58	gly	glycoproteins	259:271	arg1	immunoglobulins					292:306	immunoglobulins	292:306	immunoglobulins	292:306	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	1	58	gly	glycoproteins	259:271	arg1	glycoproteins					259:271	host-derived glycoproteins	246:271	host-derived glycoproteins such as mucins and immunoglobulins	246:306	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	9	59	theme	local	2226:2230	arg1	fluctuations					2378:2389	known ecological fluctuations	2361:2389	known ecological fluctuations prominently associated with progression toward disease	2361:2444	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	59	theme	local	2226:2230	arg1	accumulation					2279:2290	the accumulation	2275:2290	the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci	2275:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	59	theme	local	2226:2230	arg1	pH					2232:2233	increased local pH	2216:2233	increased local pH	2216:2233	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	59	theme	local	2226:2230	arg1	shift					2238:2242	a shift	2236:2242	a shift to anaerobic surroundings	2236:2268	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	4	60	theme	large	1188:1192	arg1	granules					1208:1215	large intracellular granules	1188:1215	large intracellular granules	1188:1215	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	8	61	theme	large	1967:1971	arg1	perturbations					2043:2055	large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations	1967:2055	large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations	1967:2055	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	1	62	theme	periodontal	216:226	arg1	pocket					228:233	the periodontal pocket	212:233	the periodontal pocket	212:233	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	11	63	from	shift	2600:2604	arg1	structure					2619:2627	community structure	2609:2627	community structure	2609:2627	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	7	64	theme	cell	1722:1725	arg1	shape					1727:1731	cell shape	1722:1731	cell shape	1722:1731	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	9	65	from	expense	2326:2332	arg1	fluctuations					2378:2389	known ecological fluctuations	2361:2389	known ecological fluctuations prominently associated with progression toward disease	2361:2444	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	65	from	expense	2326:2332	arg1	accumulation					2279:2290	the accumulation	2275:2290	the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci	2275:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	65	from	expense	2326:2332	arg1	pH					2232:2233	increased local pH	2216:2233	increased local pH	2216:2233	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	65	from	expense	2326:2332	arg1	shift					2238:2242	a shift	2236:2242	a shift to anaerobic surroundings	2236:2268	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	3	66	theme	individual	593:602	arg1	l-fucose					642:649	l-fucose	642:649	l-fucose	642:649	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	3	66	theme	individual	593:602	arg1	monosaccharides					604:618	individual monosaccharides	593:618	individual monosaccharides	593:618	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	3	66	theme	individual	593:602	arg1	galactose					631:639	galactose	631:639	galactose	631:639	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	3	66	theme	individual	593:602	arg1	mannose					652:658	mannose	652:658	mannose	652:658	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	3	66	theme	individual	593:602	arg1	glucose					665:671	glucose	665:671	glucose	665:671	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	7	67	theme	important	1708:1716	arg1	genes					1702:1706	genes	1702:1706	genes important for cell shape and for the general stress response	1702:1767	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	4	68	theme	individual	1155:1164	arg1	cells					1166:1170	individual cells	1155:1170	individual cells which contained large intracellular granules	1155:1215	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	11	69	theme	microbiota	2888:2897	arg1	state					2863:2867	the physiological state	2845:2867	the physiological state of the subgingival microbiota	2845:2897	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	9	70	theme	anaerobic	2247:2255	arg1	surroundings					2257:2268	anaerobic surroundings	2247:2268	anaerobic surroundings	2247:2268	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	4	71	from	plating	974:980	arg1	phase					1013:1017	stationary phase	1002:1017	stationary phase	1002:1017	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	11	72	gly	glycoproteins	2773:2785	arg1	glycoproteins					2773:2785	glycoproteins	2773:2785	glycoproteins	2773:2785	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	1	73	theme	host-derived	246:257	arg1	mucins					281:286	mucins	281:286	mucins	281:286	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	1	73	theme	host-derived	246:257	arg1	immunoglobulins					292:306	immunoglobulins	292:306	immunoglobulins	292:306	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	1	73	theme	host-derived	246:257	arg1	glycoproteins					259:271	host-derived glycoproteins	246:271	host-derived glycoproteins such as mucins and immunoglobulins	246:306	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	10	74	from	alterations	2477:2487	arg1	sites					2525:2529	disease sites	2517:2529	disease sites	2517:2529	Importantly, in contrast, the alterations to subgingival food webs in disease sites remain poorly characterized.
30552185	3	75	theme	culture	812:818	arg1	density					787:793	the density	783:793	the density of the bacterial culture	783:818	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	8	76	theme	granules.IMPORTANCE	2009:2027	arg1	perturbations					2043:2055	large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations	1967:2055	large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations	1967:2055	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	4	77	from	micrographs	958:968	arg1	phase					1013:1017	stationary phase	1002:1017	stationary phase	1002:1017	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	1	78	theme	asaccharolytic	125:138	arg1	gingivalis					163:172	The asaccharolytic anaerobe Porphyromonas gingivalis	121:172	The asaccharolytic anaerobe Porphyromonas gingivalis	121:172	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	12	79	theme	pathogen	3091:3098	arg1	physiology					3060:3069	physiology	3060:3069	physiology	3060:3069	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	12	79	theme	pathogen	3091:3098	arg1	growth					3049:3054	growth	3049:3054	growth	3049:3054	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	9	80	from	fluctuations	2378:2389	arg1	case					2187:2190	the case	2183:2190	the case of periodontal disease	2183:2213	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	1	81	theme	Porphyromonas	149:161	arg1	gingivalis					163:172	The asaccharolytic anaerobe Porphyromonas gingivalis	121:172	The asaccharolytic anaerobe Porphyromonas gingivalis	121:172	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	3	82	theme	higher	894:899	arg1	densities					901:909	significantly higher densities	880:909	significantly higher densities	880:909	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	7	83	theme	late	1664:1667	arg1	phase					1681:1685	late exponential phase	1664:1685	late exponential phase	1664:1685	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	12	84	theme	dysbiotic	3021:3029	arg1	conditions					3031:3040	dysbiotic conditions	3021:3040	dysbiotic conditions	3021:3040	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	6	85	theme	immunosorbent	1460:1472	arg1	ELISA					1481:1485	ELISA	1481:1485	ELISA	1481:1485	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	6	85	theme	immunosorbent	1460:1472	arg1	assay					1474:1478	an enzyme-linked immunosorbent assay	1443:1478	an enzyme-linked immunosorbent assay (ELISA)	1443:1486	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	8	86	theme	present	1850:1856	arg1	monosaccharide					1826:1839	a monosaccharide	1824:1839	a monosaccharide commonly present on the surfaces of host proteins	1824:1889	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	8	86	theme	present	1850:1856	arg1	galactose					1813:1821	galactose	1813:1821	galactose	1813:1821	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	9	87	theme	anaerobes	2309:2317	arg1	fluctuations					2378:2389	known ecological fluctuations	2361:2389	known ecological fluctuations prominently associated with progression toward disease	2361:2444	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	87	theme	anaerobes	2309:2317	arg1	accumulation					2279:2290	the accumulation	2275:2290	the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci	2275:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	87	theme	anaerobes	2309:2317	arg1	pH					2232:2233	increased local pH	2216:2233	increased local pH	2216:2233	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	9	87	theme	anaerobes	2309:2317	arg1	shift					2238:2242	a shift	2236:2242	a shift to anaerobic surroundings	2236:2268	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	0	88	theme	Pathobiont	84:93	arg1	gingivalis					109:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis	60:118	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	2	89	theme	proteinaceous	528:540	arg1	core					542:545	the proteinaceous core	524:545	the proteinaceous core	524:545	Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and P. gingivalis produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core.
30552185	3	90	from	effect	583:588	arg1	physiology					692:701	physiology	692:701	physiology	692:701	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	3	90	from	effect	583:588	arg1	growth					681:686	growth	681:686	growth	681:686	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	0	91	theme	gingivalis	109:118	arg1	Size					22:25	Size	22:25	Size	22:25	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	0	91	theme	gingivalis	109:118	arg1	Composition					45:55	Intracellular Composition	31:55	Intracellular Composition	31:55	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	7	92	theme	transcriptional	1615:1629	arg1	changes					1631:1637	the transcriptional changes	1611:1637	the transcriptional changes elicited by galactose in late exponential phase	1611:1685	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	4	93	theme	P.	985:986	arg1	gingivalis					988:997	P. gingivalis	985:997	P. gingivalis	985:997	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	6	94	theme	polysaccharides	1423:1437	arg1	analysis					1397:1404	an analysis	1394:1404	an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA)	1394:1486	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	6	95	theme	major	1409:1413	arg1	polysaccharides					1423:1437	major surface polysaccharides	1409:1437	major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA)	1409:1486	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	8	96	theme	proteins	1882:1889	arg1	surfaces					1865:1872	the surfaces	1861:1872	the surfaces of host proteins	1861:1889	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	12	97	theme	free	2941:2944	arg1	monosaccharides					2946:2960	free monosaccharides	2941:2960	free monosaccharides	2941:2960	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	11	98	theme	dramatic	2591:2598	arg1	shift					2600:2604	the dramatic shift	2587:2604	the dramatic shift in community structure during disease	2587:2642	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	9	99	theme	cocci	2351:2355	arg1	expense					2326:2332	the expense	2322:2332	the expense of Gram-positive cocci	2322:2355	In the case of periodontal disease, increased local pH, a shift to anaerobic surroundings, and the accumulation of Gram-negative anaerobes at the expense of Gram-positive cocci are known ecological fluctuations prominently associated with progression toward disease.
30552185	6	100	theme	significant	1503:1513	arg1	differences					1515:1525	significant differences	1503:1525	significant differences between cells grown with or without galactose	1503:1571	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	12	101	from	impact	2931:2936	arg1	gingivalis					2968:2977	P. gingivalis	2965:2977	P. gingivalis	2965:2977	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	11	102	theme	community	2609:2617	arg1	structure					2619:2627	community structure	2609:2627	community structure	2609:2627	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	8	103	theme	sites	2173:2177	arg1	development					2149:2159	the development	2145:2159	the development of diseased sites	2145:2177	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	11	104	theme	Gram-positive	2733:2745	arg1	cocci					2747:2751	Gram-positive cocci	2733:2751	Gram-positive cocci	2733:2751	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	2	105	theme	glycolytic	419:428	arg1	bonds					430:434	glycolytic bonds	419:434	glycolytic bonds	419:434	Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and P. gingivalis produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core.
30552185	7	106	theme	general	1745:1751	arg1	response					1760:1767	the general stress response	1741:1767	the general stress response	1741:1767	Finally, an initial investigation of the transcriptional changes elicited by galactose in late exponential phase suggested that genes important for cell shape and for the general stress response may play roles in this phenomenon.
30552185	2	107	theme	capable	472:478	arg1	enzymes					464:470	enzymes	464:470	enzymes capable of liberating these carbohydrates	464:512	Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and P. gingivalis produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core.
30552185	1	108	dep	proteins	186:193	arg1	it					195:196	it	195:196	it	195:196	The asaccharolytic anaerobe Porphyromonas gingivalis metabolizes proteins it encounters in the periodontal pocket, including host-derived glycoproteins such as mucins and immunoglobulins.
30552185	12	109	theme	conditions	3031:3040	arg1	effect					3011:3016	the effect	3007:3016	the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen	3007:3098	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	0	110	theme	Intracellular	31:43	arg1	Composition					45:55	Intracellular Composition	31:55	Intracellular Composition	31:55	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	8	111	attach	present	1850:1856	arg2	galactose					1813:1821	galactose	1813:1821	galactose	1813:1821	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	8	111	attach	present	1850:1856	arg1	surfaces					1865:1872	the surfaces	1861:1872	the surfaces of host proteins	1861:1889	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	8	111	attach	present	1850:1856	arg2	monosaccharide					1826:1839	a monosaccharide	1824:1839	a monosaccharide commonly present on the surfaces of host proteins	1824:1889	Overall, galactose, a monosaccharide commonly present on the surfaces of host proteins, substantially alters the physiology of P. gingivalis via the production of large, currently undefined, intracellular granules.IMPORTANCE Environmental perturbations are central to the ability of pathobionts, such as Porphyromonas gingivalis, to promote the development of diseased sites.
30552185	2	112	theme	P.	441:442	arg1	gingivalis					444:453	P. gingivalis	441:453	P. gingivalis	441:453	Often, these proteins are protected by a diverse array of carbohydrates tethered to the polypeptide chain via glycolytic bonds, and P. gingivalis produces enzymes capable of liberating these carbohydrates, exposing the proteinaceous core.
30552185	4	113	contain	contained	1178:1186	arg2	granules					1208:1215	large intracellular granules	1188:1215	large intracellular granules	1188:1215	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	4	113	contain	contained	1178:1186	arg1	cells					1166:1170	individual cells	1155:1170	individual cells which contained large intracellular granules	1155:1215	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	4	114	theme	galactose	1053:1061	arg1	presence					1041:1048	the presence	1037:1048	the presence of galactose	1037:1061	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	12	115	from	effect	3011:3016	arg1	physiology					3060:3069	physiology	3060:3069	physiology	3060:3069	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	12	115	from	effect	3011:3016	arg1	growth					3049:3054	growth	3049:3054	growth	3049:3054	In this study, we explored the impact of free monosaccharides on P. gingivalis to gain deeper insight into the effect of dysbiotic conditions on the growth and physiology of this periodontal pathogen.
30552185	0	116	dep	Size	22:25	arg1	the					18:20	the	18:20	the	18:20	Galactose Impacts the Size and Intracellular Composition of the Asaccharolytic Oral Pathobiont Porphyromonas gingivalis.
30552185	4	117	theme	higher	1107:1112	arg1	densities					1114:1122	the higher densities	1103:1122	the higher densities	1103:1122	Importantly, electron micrographs and plating of P. gingivalis in stationary phase demonstrated that the presence of galactose did not increase cell numbers; instead, the higher densities resulted from the expansion of individual cells which contained large intracellular granules.
30552185	6	118	theme	surface	1415:1421	arg1	polysaccharides					1423:1437	major surface polysaccharides	1409:1437	major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA)	1409:1486	Also, an analysis of major surface polysaccharides via an enzyme-linked immunosorbent assay (ELISA) did not reveal significant differences between cells grown with or without galactose.
30552185	11	119	theme	free	2665:2668	arg1	carbohydrates					2670:2682	free carbohydrates	2665:2682	free carbohydrates	2665:2682	We hypothesized that given the dramatic shift in community structure during disease, it is possible that free carbohydrates, which would typically be readily metabolized by Gram-positive cocci after cleavage from glycoproteins, may increase in concentration locally and thereby affect the physiological state of the subgingival microbiota.
30552185	3	120	dep	growth	681:686	arg1	the					677:679	the	677:679	the	677:679	In this study, we investigated the effect of individual monosaccharides, including galactose, l-fucose, mannose, and glucose, on the growth and physiology of P. gingivalis Of the carbohydrates tested, only galactose noticeably altered the density of the bacterial culture, and we observed that cultures grown with galactose reached significantly higher densities during stationary phase.
30552185	5	121	theme	soluble	1301:1307	arg1	carbohydrates					1309:1321	soluble carbohydrates	1301:1321	soluble carbohydrates	1301:1321	Initial attempts to characterize these granules revealed only a subtle increase in soluble carbohydrates, suggesting they are likely not composed of stored carbohydrate.
31032817	0	0	theme	Binding	90:96	arg1	Domains					98:104	Binding Domains	90:104	Binding Domains	90:104	Intrinsically Disordered Linkers Impart Processivity on Enzymes by Spatial Confinement of Binding Domains.
31032817	5	1	theme	effective	1068:1076	arg1	concentration					1078:1090	an optimized effective concentration	1055:1090	an optimized effective concentration around novel binding site(s)	1055:1119	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	3	2	theme	molecular	694:702	arg1	events					704:709	molecular events	694:709	molecular events	694:709	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	3	2	theme	molecular	694:702	arg1	motors					741:746	mechanochemical motors	725:746	mechanochemical motors	725:746	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	2	3	theme	multiple	331:338	arg1	rounds					340:345	multiple rounds	331:345	multiple rounds of modification	331:361	Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely effective and economical.
31032817	1	4	theme	polymeric	234:242	arg1	substrates					244:253	polymeric substrates	234:253	polymeric substrates	234:253	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	7	5	with	composition	1494:1504	arg1	size					1564:1567	step size	1559:1567	step size	1559:1567	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	6	theme	special	1475:1481	arg1	composition					1494:1504	special amino acid composition	1475:1504	special amino acid composition of linkers	1475:1515	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	7	theme	disorder	1465:1472	arg1	conservation					1438:1449	a conservation	1436:1449	a conservation of structural disorder	1436:1472	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	7	theme	disorder	1465:1472	arg1	correlation					1526:1536	the correlation	1522:1536	the correlation of their length with step size	1522:1567	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	7	theme	disorder	1465:1472	arg1	composition					1494:1504	special amino acid composition	1475:1504	special amino acid composition of linkers	1475:1515	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	4	8	theme	elements	857:864	arg1	confinement					830:840	spatial confinement	822:840	spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker	822:917	Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker.
31032817	6	9	theme	kinetic	1337:1343	arg1	parameters					1345:1354	the kinetic parameters	1333:1354	the kinetic parameters of binding elements	1333:1374	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	5	10	theme	full	1146:1149	arg1	release					1151:1157	full release	1146:1157	full release of the polymeric partner	1146:1182	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	0	11	theme	Domains	98:104	arg1	Confinement					75:85	Spatial Confinement	67:85	Spatial Confinement of Binding Domains	67:104	Intrinsically Disordered Linkers Impart Processivity on Enzymes by Spatial Confinement of Binding Domains.
31032817	3	12	theme	events	704:709	arg1	succession					680:689	the succession	676:689	the succession of molecular events, such as with mechanochemical motors	676:746	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	4	13	theme	binding	849:855	arg1	elements					857:864	two binding elements	845:864	two binding elements connected by an intrinsically disordered (ID) linker	845:917	Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker.
31032817	8	14	theme	ID	1657:1658	arg1	proteins					1660:1667	ID proteins	1657:1667	ID proteins	1657:1667	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	3	15	dep	cases	532:536	arg1	confines					567:574	confines	567:574	confines the substrate, such as the DNA replication factor PCNA	567:629	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	3	15	dep	cases	532:536	arg1	used					660:663	used	660:663	is used to confine the succession of molecular events, such as with mechanochemical motors	657:746	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	8	16	theme	biological	1743:1752	arg1	contexts					1754:1761	biological contexts	1743:1761	biological contexts	1743:1761	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	8	17	theme	contexts	1754:1761	arg1	variety					1732:1738	a variety	1730:1738	a variety of biological contexts	1730:1761	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	8	17	theme	contexts	1754:1761	arg1	contexts					1754:1761	biological contexts	1743:1761	biological contexts	1743:1761	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	8	18	dep	Conclusion	1574:1583	arg1	suggest					1605:1611	suggest	1605:1611	suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts	1605:1761	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	8	18	dep	Conclusion	1574:1583	arg1	4					1571:1571	4	1571:1571	4	1571:1571	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	4	19	dep	disordered	896:905	arg1	ID					908:909	ID	908:909	ID	908:909	Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker.
31032817	6	20	dep	illustrate	1264:1273	arg1	3					1186:1186	3	1186:1186	3	1186:1186	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	7	21	theme	structural	1454:1463	arg1	disorder					1465:1472	structural disorder	1454:1472	structural disorder	1454:1472	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	1	22	dep	Background	111:120	arg1	common					139:144	common	139:144	common	139:144	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	1	22	dep	Background	111:120	arg1	1					108:108	1	108:108	1	108:108	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	1	23	theme	mechanochemical	164:178	arg1	motors					180:185	mechanochemical motors	164:185	mechanochemical motors	164:185	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	1	23	theme	mechanochemical	164:178	arg1	polysaccharides					274:288	polysaccharides	274:288	polysaccharides	274:288	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	1	23	theme	mechanochemical	164:178	arg1	RNA					269:271	RNA	269:271	RNA	269:271	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	1	23	theme	mechanochemical	164:178	arg1	DNA					264:266	DNA	264:266	DNA	264:266	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	1	23	theme	mechanochemical	164:178	arg1	proteins					293:300	proteins	293:300	proteins	293:300	(1) Background: Processivity is common among enzymes and mechanochemical motors that synthesize, degrade, modify or move along polymeric substrates, such as DNA, RNA, polysaccharides or proteins.
31032817	0	24	theme	Disordered	14:23	arg1	Linkers					25:31	Intrinsically Disordered Linkers	0:31	Intrinsically Disordered Linkers	0:31	Intrinsically Disordered Linkers Impart Processivity on Enzymes by Spatial Confinement of Binding Domains.
31032817	0	25	from	Processivity	40:51	arg1	Enzymes					56:62	Enzymes	56:62	Enzymes	56:62	Intrinsically Disordered Linkers Impart Processivity on Enzymes by Spatial Confinement of Binding Domains.
31032817	8	26	theme	functional	1686:1695	arg1	advantages					1697:1706	functional advantages	1686:1706	functional advantages	1686:1706	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	2	27	theme	effective	437:445	arg1	operation					417:425	their operation	411:425	their operation extremely effective and economical	411:460	Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely effective and economical.
31032817	4	28	theme	spatial	822:828	arg1	confinement					830:840	spatial confinement	822:840	spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker	822:917	Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker.
31032817	7	29	with	correlation	1526:1536	arg1	size					1564:1567	step size	1559:1567	step size	1559:1567	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	2	30	theme	modification	350:361	arg1	rounds					340:345	multiple rounds	331:345	multiple rounds of modification	331:361	Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely effective and economical.
31032817	3	31	theme	mechanochemical	725:739	arg1	motors					741:746	mechanochemical motors	725:746	mechanochemical motors	725:746	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	7	32	theme	step	1559:1562	arg1	size					1564:1567	step size	1559:1567	step size	1559:1567	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	8	33	theme	function	1645:1652	arg1	type					1622:1625	a unique type	1613:1625	a unique type	1613:1625	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	4	34	theme	disordered	896:905	arg1	linker					912:917	an intrinsically disordered (ID) linker	879:917	an intrinsically disordered (ID) linker	879:917	Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker.
31032817	8	35	theme	unique	1615:1620	arg1	type					1622:1625	a unique type	1613:1625	a unique type	1613:1625	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	3	36	theme	molecular	467:475	arg1	mechanism					477:485	The molecular mechanism	463:485	The molecular mechanism of processivity	463:501	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	8	37	from	enzymes	1719:1725	arg1	variety					1732:1738	a variety	1730:1738	a variety of biological contexts	1730:1761	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	8	37	from	enzymes	1719:1725	arg1	contexts					1754:1761	biological contexts	1743:1761	biological contexts	1743:1761	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	7	38	theme	length	1547:1552	arg1	conservation					1438:1449	a conservation	1436:1449	a conservation of structural disorder	1436:1472	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	38	theme	length	1547:1552	arg1	correlation					1526:1536	the correlation	1522:1536	the correlation of their length with step size	1522:1567	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	38	theme	length	1547:1552	arg1	composition					1494:1504	special amino acid composition	1475:1504	special amino acid composition of linkers	1475:1515	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	5	39	theme	novel	1099:1103	arg1	site					1113:1116	novel binding site	1099:1116	novel binding site(s)	1099:1119	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	5	39	theme	novel	1099:1103	arg1	s					1118:1118	s	1118:1118	s	1118:1118	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	4	40	theme	kinetic	787:793	arg1	bias					795:798	the kinetic bias	783:798	the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker	783:917	Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker.
31032817	7	41	with	conservation	1438:1449	arg1	size					1564:1567	step size	1559:1567	step size	1559:1567	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	8	42	theme	diverse	1711:1717	arg1	enzymes					1719:1725	diverse enzymes	1711:1725	diverse enzymes in a variety of biological contexts	1711:1761	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	6	43	theme	linker	1298:1303	arg1	length					1305:1310	linker length	1298:1310	linker length	1298:1310	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	5	44	theme	binding	1105:1111	arg1	site					1113:1116	novel binding site	1099:1116	novel binding site(s)	1099:1119	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	5	44	theme	binding	1105:1111	arg1	s					1118:1118	s	1118:1118	s	1118:1118	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	4	45	theme	binding	803:809	arg1	bias					795:798	the kinetic bias	783:798	the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker	783:917	Processivity may also result from the kinetic bias of binding imposed by spatial confinement of two binding elements connected by an intrinsically disordered (ID) linker.
31032817	3	46	theme	processivity	490:501	arg1	mechanism					477:485	The molecular mechanism	463:485	The molecular mechanism of processivity	463:501	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	2	47	theme	economical	451:460	arg1	operation					417:425	their operation	411:425	their operation extremely effective and economical	411:460	Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely effective and economical.
31032817	3	48	used	used	660:663	arg2	energy					650:655	ATP energy	646:655	ATP energy	646:655	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	8	49	theme	chain	1639:1643	arg1	function					1645:1652	entropic chain function	1630:1652	entropic chain function of ID proteins	1630:1667	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	6	50	theme	such	1214:1217	arg1	proteins					1219:1226	12 such proteins	1211:1226	12 such proteins	1211:1226	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	6	50	theme	such	1214:1217	arg1	cellulase					1237:1245	cellulase	1237:1245	cellulase	1237:1245	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	5	51	theme	statistical	935:945	arg1	modeling					956:963	statistical physical modeling	935:963	statistical physical modeling	935:963	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	3	52	theme	factor	619:624	arg1	PCNA					626:629	the DNA replication factor PCNA	599:629	the DNA replication factor PCNA	599:629	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	8	53	theme	entropic	1630:1637	arg1	function					1645:1652	entropic chain function	1630:1652	entropic chain function of ID proteins	1630:1667	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	2	54	theme	Processive	303:312	arg1	enzymes					314:320	Processive enzymes	303:320	Processive enzymes	303:320	Processive enzymes can make multiple rounds of modification without releasing the substrate/partner, making their operation extremely effective and economical.
31032817	7	55	theme	amino	1483:1487	arg1	composition					1494:1504	special amino acid composition	1475:1504	special amino acid composition of linkers	1475:1515	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	3	56	theme	ATP	646:648	arg1	energy					650:655	ATP energy	646:655	ATP energy	646:655	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	5	57	theme	physical	947:954	arg1	modeling					956:963	statistical physical modeling	935:963	statistical physical modeling	935:963	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	5	58	dep	Method	924:929	arg1	show					969:972	show	969:972	show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner	969:1182	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	7	59	theme	acid	1489:1492	arg1	composition					1494:1504	special amino acid composition	1475:1504	special amino acid composition of linkers	1475:1515	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	5	60	theme	processive	1007:1016	arg1	systems					1018:1024	processive systems	1007:1024	processive systems	1007:1024	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	3	61	theme	DNA	603:605	arg1	PCNA					626:629	the DNA replication factor PCNA	599:629	the DNA replication factor PCNA	599:629	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	7	62	theme	linkers	1509:1515	arg1	conservation					1438:1449	a conservation	1436:1449	a conservation of structural disorder	1436:1472	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	62	theme	linkers	1509:1515	arg1	correlation					1526:1536	the correlation	1522:1536	the correlation of their length with step size	1522:1567	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	7	62	theme	linkers	1509:1515	arg1	composition					1494:1504	special amino acid composition	1475:1504	special amino acid composition of linkers	1475:1515	We also report a conservation of structural disorder, special amino acid composition of linkers, and the correlation of their length with step size.
31032817	6	63	theme	elements	1367:1374	arg1	length					1305:1310	linker length	1298:1310	linker length	1298:1310	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	6	63	theme	elements	1367:1374	arg1	parameters					1345:1354	the kinetic parameters	1333:1354	the kinetic parameters of binding elements	1333:1374	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	6	63	theme	elements	1367:1374	arg1	flexibility					1316:1326	flexibility	1316:1326	flexibility	1316:1326	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	5	64	theme	polymeric	1166:1174	arg1	partner					1176:1182	the polymeric partner	1162:1182	the polymeric partner	1162:1182	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	0	65	theme	Spatial	67:73	arg1	Confinement					75:85	Spatial Confinement	67:85	Spatial Confinement of Binding Domains	67:104	Intrinsically Disordered Linkers Impart Processivity on Enzymes by Spatial Confinement of Binding Domains.
31032817	5	66	theme	optimized	1058:1066	arg1	concentration					1078:1090	an optimized effective concentration	1055:1090	an optimized effective concentration around novel binding site(s)	1055:1119	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31032817	3	67	theme	replication	607:617	arg1	PCNA					626:629	the DNA replication factor PCNA	599:629	the DNA replication factor PCNA	599:629	The molecular mechanism of processivity is rather well understood in cases when the enzyme structurally confines the substrate, such as the DNA replication factor PCNA, and also when ATP energy is used to confine the succession of molecular events, such as with mechanochemical motors.
31032817	8	68	theme	proteins	1660:1667	arg1	function					1645:1652	entropic chain function	1630:1652	entropic chain function of ID proteins	1630:1667	(4) Conclusion: These observations suggest a unique type of entropic chain function of ID proteins, that may impart functional advantages on diverse enzymes in a variety of biological contexts.
31032817	6	69	theme	binding	1359:1365	arg1	elements					1367:1374	binding elements	1359:1374	binding elements	1359:1374	(3) Results: By analyzing 12 such proteins, such as cellulase, and RNAse-H, we illustrate that in these proteins linker length and flexibility, and the kinetic parameters of binding elements, are fine-tuned for optimizing processivity.
31032817	5	70	theme	partner	1176:1182	arg1	release					1151:1157	full release	1146:1157	full release of the polymeric partner	1146:1182	(2) Method: By statistical physical modeling, we show that this arrangement results in processive systems, in which the linker ensures an optimized effective concentration around novel binding site(s), favoring rebinding over full release of the polymeric partner.
31827688	1	0	link	O-linked	90:97	arg1	β-N-acetylglucosamine					99:119	O-linked β-N-acetylglucosamine	90:119	O-linked β-N-acetylglucosamine (O-GlcNAcylation)	90:137	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	0	link	O-linked	90:97	arg1	O-GlcNAcylation					122:136	O-GlcNAcylation	122:136	O-GlcNAcylation	122:136	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	4	1	theme	LC3-II	1010:1015	arg1	protein					1017:1023	LC3-II protein	1010:1023	LC3-II protein	1010:1023	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	6	2	theme	substrate	1437:1445	arg1	SQSTM1/p62					1447:1456	autophagy substrate SQSTM1/p62	1427:1456	autophagy substrate SQSTM1/p62	1427:1456	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	5	3	theme	OGT	1123:1125	arg1	knockdown					1127:1135	OGT knockdown	1123:1135	OGT knockdown	1123:1135	In particular, we found that OGT knockdown increases the fusion between autophagosomes as well as lysosomes and stimulates autophagy to promote lysosomal-associated membrane protein 1 (LAMP-1).
31827688	5	4	theme	lysosomal-associated	1238:1257	arg1	protein					1268:1274	lysosomal-associated membrane protein 1	1238:1276	lysosomal-associated membrane protein 1 (LAMP-1)	1238:1285	In particular, we found that OGT knockdown increases the fusion between autophagosomes as well as lysosomes and stimulates autophagy to promote lysosomal-associated membrane protein 1 (LAMP-1).
31827688	5	4	theme	lysosomal-associated	1238:1257	arg1	LAMP-1					1279:1284	LAMP-1	1279:1284	LAMP-1	1279:1284	In particular, we found that OGT knockdown increases the fusion between autophagosomes as well as lysosomes and stimulates autophagy to promote lysosomal-associated membrane protein 1 (LAMP-1).
31827688	6	5	theme	autophagy	1427:1435	arg1	SQSTM1/p62					1447:1456	autophagy substrate SQSTM1/p62	1427:1456	autophagy substrate SQSTM1/p62	1427:1456	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	3	6	theme	OGA	719:721	arg1	siRNA					723:727	OGA siRNA	719:727	OGA siRNA	719:727	Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
31827688	5	7	theme	membrane	1259:1266	arg1	protein					1268:1274	lysosomal-associated membrane protein 1	1238:1276	lysosomal-associated membrane protein 1 (LAMP-1)	1238:1285	In particular, we found that OGT knockdown increases the fusion between autophagosomes as well as lysosomes and stimulates autophagy to promote lysosomal-associated membrane protein 1 (LAMP-1).
31827688	5	7	theme	membrane	1259:1266	arg1	LAMP-1					1279:1284	LAMP-1	1279:1284	LAMP-1	1279:1284	In particular, we found that OGT knockdown increases the fusion between autophagosomes as well as lysosomes and stimulates autophagy to promote lysosomal-associated membrane protein 1 (LAMP-1).
31827688	1	8	dep	serine	142:147	arg1	residues					163:170	residues	163:170	residues	163:170	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	7	9	theme	mouse	1632:1636	arg1	astrocytes					1647:1656	mouse cortical astrocytes	1632:1656	mouse cortical astrocytes	1632:1656	Together, our study reveals a mechanism by which the modulation of O-GlcNAcylation modification regulates autophagy in mouse cortical astrocytes.
31827688	1	10	theme	O-GlcNAcylation	370:384	arg1	transferase					386:396	O-GlcNAcylation transferase	370:396	O-GlcNAcylation transferase (OGT)	370:402	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	10	theme	O-GlcNAcylation	370:384	arg1	OGT					399:401	OGT	399:401	OGT	399:401	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	7	11	theme	cortical	1638:1645	arg1	astrocytes					1647:1656	mouse cortical astrocytes	1632:1656	mouse cortical astrocytes	1632:1656	Together, our study reveals a mechanism by which the modulation of O-GlcNAcylation modification regulates autophagy in mouse cortical astrocytes.
31827688	2	12	theme	O-GlcNAcylation	523:537	arg1	modification					539:550	O-GlcNAcylation modification	523:550	O-GlcNAcylation modification	523:550	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	1	13	theme	transferase	386:396	arg1	pair					330:333	a single pair	321:333	a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT)	321:402	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	2	14	theme	recycling	429:437	arg1	Autophagy					405:413	Autophagy	405:413	Autophagy	405:413	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	2	14	theme	recycling	429:437	arg1	pathway					439:445	a cellular recycling pathway	418:445	a cellular recycling pathway activated by stress and nutrient signaling	418:488	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	1	15	theme	common	177:182	arg1	modification					202:213	a common posttranslational modification	175:213	a common posttranslational modification	175:213	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	15	theme	common	177:182	arg1	addition					78:85	The addition	74:85	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues	74:170	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	0	16	theme	Cortical	53:60	arg1	Astrocytes					62:71	Cortical Astrocytes	53:71	Cortical Astrocytes	53:71	Modulation of O-GlcNAcylation Regulates Autophagy in Cortical Astrocytes.
31827688	6	17	theme	decreasing	1302:1311	arg1	O-GlcNAcylation					1313:1327	decreasing O-GlcNAcylation	1302:1327	decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression	1302:1388	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	1	18	theme	posttranslational	184:200	arg1	modification					202:213	a common posttranslational modification	175:213	a common posttranslational modification	175:213	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	18	theme	posttranslational	184:200	arg1	addition					78:85	The addition	74:85	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues	74:170	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	0	19	from	Autophagy	40:48	arg1	Astrocytes					62:71	Cortical Astrocytes	53:71	Cortical Astrocytes	53:71	Modulation of O-GlcNAcylation Regulates Autophagy in Cortical Astrocytes.
31827688	4	20	theme	LC3	896:898	arg1	puncta					900:905	LC3 puncta	896:905	LC3 puncta	896:905	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	1	21	theme	O-linked	90:97	arg1	β-N-acetylglucosamine					99:119	O-linked β-N-acetylglucosamine	90:119	O-linked β-N-acetylglucosamine (O-GlcNAcylation)	90:137	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	21	theme	O-linked	90:97	arg1	O-GlcNAcylation					122:136	O-GlcNAcylation	122:136	O-GlcNAcylation	122:136	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	4	22	theme	decreased	1042:1050	arg1	O-GlcNAcylation					1052:1066	decreased O-GlcNAcylation	1042:1066	decreased O-GlcNAcylation	1042:1066	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	1	23	theme	β-N-acetylglucosamine	99:119	arg1	addition					78:85	The addition	74:85	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues	74:170	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	23	theme	β-N-acetylglucosamine	99:119	arg1	modification					202:213	a common posttranslational modification	175:213	a common posttranslational modification	175:213	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	4	24	theme	autophagic	1077:1086	arg1	flux					1088:1091	autophagic flux	1077:1091	autophagic flux	1077:1091	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	1	25	theme	single	323:328	arg1	pair					330:333	a single pair	321:333	a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT)	321:402	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	26	theme	intracellular	218:230	arg1	proteins					232:239	intracellular proteins	218:239	intracellular proteins which modulates protein functions and neurodegenerative diseases	218:304	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	0	27	theme	O-GlcNAcylation	14:28	arg1	Modulation					0:9	Modulation	0:9	Modulation of O-GlcNAcylation	0:28	Modulation of O-GlcNAcylation Regulates Autophagy in Cortical Astrocytes.
31827688	3	28	theme	decreased	763:771	arg1	O-GlcNAcylation					773:787	decreased O-GlcNAcylation	763:787	decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA	763:837	Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
31827688	2	29	theme	cortical	575:582	arg1	astrocytes					584:593	cortical astrocytes	575:593	cortical astrocytes	575:593	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	6	30	with	treatment	1332:1340	arg1	siRNA					1360:1364	OGT siRNA	1356:1364	OGT siRNA	1356:1364	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	6	30	with	treatment	1332:1340	arg1	overexpression					1375:1388	OGA overexpression	1371:1388	OGA overexpression	1371:1388	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	6	30	with	treatment	1332:1340	arg1	alloxan					1347:1353	alloxan	1347:1353	alloxan	1347:1353	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	1	31	theme	proteins	232:239	arg1	modification					202:213	a common posttranslational modification	175:213	a common posttranslational modification	175:213	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	1	31	theme	proteins	232:239	arg1	addition					78:85	The addition	74:85	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues	74:170	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	4	32	theme	autophagy	950:958	arg1	inhibitor					960:968	an autophagy inhibitor	947:968	an autophagy inhibitor	947:968	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	4	32	theme	autophagy	950:958	arg1	chloroquine					929:939	chloroquine	929:939	chloroquine (CQ)	929:944	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	3	33	theme	OGA	686:688	arg1	activity					690:697	OGA activity	686:697	OGA activity	686:697	Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
31827688	2	34	theme	cellular	420:427	arg1	Autophagy					405:413	Autophagy	405:413	Autophagy	405:413	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	2	34	theme	cellular	420:427	arg1	pathway					439:445	a cellular recycling pathway	418:445	a cellular recycling pathway activated by stress and nutrient signaling	418:488	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	6	35	theme	autophagic	1475:1484	arg1	degradation					1486:1496	autophagic degradation	1475:1496	autophagic degradation	1475:1496	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	1	36	theme	enzymes	338:344	arg1	pair					330:333	a single pair	321:333	a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT)	321:402	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	3	37	theme	OGT	799:801	arg1	inhibition					803:812	OGT inhibition	799:812	OGT inhibition	799:812	Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
31827688	6	38	theme	OGA	1371:1373	arg1	overexpression					1375:1388	OGA overexpression	1371:1388	OGA overexpression	1371:1388	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	2	39	theme	nutrient	471:478	arg1	signaling					480:488	nutrient signaling	471:488	nutrient signaling	471:488	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	1	40	theme	O-GlcNAcase	347:357	arg1	pair					330:333	a single pair	321:333	a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT)	321:402	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	4	41	dep	OGT	860:862	arg1	inhibitor					864:872	inhibitor	864:872	inhibitor	864:872	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	7	42	theme	modification	1596:1607	arg1	modulation					1566:1575	the modulation	1562:1575	the modulation of O-GlcNAcylation modification	1562:1607	Together, our study reveals a mechanism by which the modulation of O-GlcNAcylation modification regulates autophagy in mouse cortical astrocytes.
31827688	4	43	with	cotreatment	912:922	arg1	inhibitor					960:968	an autophagy inhibitor	947:968	an autophagy inhibitor	947:968	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	4	43	with	cotreatment	912:922	arg1	CQ					942:943	CQ	942:943	CQ	942:943	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	4	43	with	cotreatment	912:922	arg1	chloroquine					929:939	chloroquine	929:939	chloroquine (CQ)	929:944	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	3	44	theme	increased	638:646	arg1	O-GlcNAcylation					648:662	increased O-GlcNAcylation	638:662	increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA	638:727	Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
31827688	6	45	theme	OGT	1356:1358	arg1	siRNA					1360:1364	OGT siRNA	1356:1364	OGT siRNA	1356:1364	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	7	46	theme	O-GlcNAcylation	1580:1594	arg1	modification					1596:1607	O-GlcNAcylation modification	1580:1607	O-GlcNAcylation modification	1580:1607	Together, our study reveals a mechanism by which the modulation of O-GlcNAcylation modification regulates autophagy in mouse cortical astrocytes.
31827688	1	47	theme	protein	257:263	arg1	functions					265:273	protein functions	257:273	protein functions	257:273	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
31827688	3	48	theme	activity	690:697	arg1	suppression					671:681	the suppression	667:681	the suppression of OGA activity using thiamet-G and OGA siRNA	667:727	Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
31827688	7	49	from	autophagy	1619:1627	arg1	astrocytes					1647:1656	mouse cortical astrocytes	1632:1656	mouse cortical astrocytes	1632:1656	Together, our study reveals a mechanism by which the modulation of O-GlcNAcylation modification regulates autophagy in mouse cortical astrocytes.
31827688	2	50	from	autophagy	562:570	arg1	astrocytes					584:593	cortical astrocytes	575:593	cortical astrocytes	575:593	Autophagy is a cellular recycling pathway activated by stress and nutrient signaling; however, the mechanism by which O-GlcNAcylation modification regulates autophagy in cortical astrocytes is poorly understood.
31827688	6	51	theme	SQSTM1/p62	1447:1456	arg1	level					1418:1422	the level	1414:1422	the level of autophagy substrate SQSTM1/p62	1414:1456	Additionally, decreasing O-GlcNAcylation by treatment with alloxan, OGT siRNA, and OGA overexpression significantly decreased the level of autophagy substrate SQSTM1/p62, indicating that autophagic degradation was activated.
31827688	4	52	theme	LC3	995:997	arg1	puncta					999:1004	LC3 puncta	995:1004	LC3 puncta	995:1004	OGT inhibitor and siRNA accumulated LC3 puncta, and cotreatment with chloroquine (CQ), an autophagy inhibitor, significantly increased LC3 puncta and LC3-II protein, confirming that decreased O-GlcNAcylation promotes autophagic flux.
31827688	3	53	theme	OGT	829:831	arg1	siRNA					833:837	OGT siRNA	829:837	OGT siRNA	829:837	Here, we report that increased O-GlcNAcylation by the suppression of OGA activity using thiamet-G and OGA siRNA did not affect autophagy, whereas decreased O-GlcNAcylation caused by OGT inhibition by alloxan and OGT siRNA increased autophagy.
31827688	1	54	theme	neurodegenerative	279:295	arg1	diseases					297:304	neurodegenerative diseases	279:304	neurodegenerative diseases	279:304	The addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) to serine and threonine residues is a common posttranslational modification of intracellular proteins which modulates protein functions and neurodegenerative diseases, controlled by a single pair of enzymes, O-GlcNAcase (OGA), and O-GlcNAcylation transferase (OGT).
30878391	10	0	from	differences	1596:1606	arg1	impala					1652:1657	the impala	1648:1657	the impala	1648:1657	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	10	1	theme	hormone	1807:1813	arg1	changes					1815:1821	the cyclical hormone changes	1794:1821	the cyclical hormone changes which induce them	1794:1839	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	2	2	theme	right	331:335	arg1	horns					354:358	right and left uterine horns	331:358	right and left uterine horns from six non-pregnant, wild impala	331:393	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	3	3	theme	ovarian	529:535	arg1	3ßHSD					570:574	3ßHSD	570:574	3ßHSD	570:574	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	3	3	theme	ovarian	529:535	arg1	dehydrogenase					555:567	ovarian 3ß hydroxysteroid dehydrogenase	529:567	ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD)	529:575	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	4	4	theme	detectable	655:664	arg1	differences					666:676	few detectable differences	651:676	few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens	651:770	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	5	theme	right	844:848	arg1	horn					850:853	the right horn	840:853	the right horn	840:853	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	3	6	theme	hydroxysteroid	540:553	arg1	3ßHSD					570:574	3ßHSD	570:574	3ßHSD	570:574	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	3	6	theme	hydroxysteroid	540:553	arg1	dehydrogenase					555:567	ovarian 3ß hydroxysteroid dehydrogenase	529:567	ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD)	529:575	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	1	7	theme	right	190:194	arg1	horn					204:207	the right uterine horn	186:207	the right uterine horn	186:207	Placentation commences only in the right uterine horn in impala (Aepyceros melampus).
30878391	1	8	dep	Aepyceros	220:228	arg1	melampus					230:237	Aepyceros melampus	220:237	Aepyceros melampus	220:237	Placentation commences only in the right uterine horn in impala (Aepyceros melampus).
30878391	0	9	theme	impala	126:131	arg1	horns					100:104	the uterine horns	88:104	the uterine horns of the non-pregnant impala	88:131	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	3	10	theme	aromatase	581:589	arg1	presence					517:524	The presence	513:524	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase	513:589	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	0	11	from	morphology	56:65	arg1	study					14:18	A preliminary study	0:18	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).	0:153	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	11	from	morphology	56:65	arg1	Aepyceros					134:142	Aepyceros	134:142	Aepyceros	134:142	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	7	12	theme	right	1278:1282	arg1	side					1284:1287	the right side	1274:1287	the right side	1274:1287	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	5	13	attach	present	934:940	arg2	clusters					895:902	Heavily glycosylated clusters	874:902	Heavily glycosylated clusters of supranuclear granules	874:927	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	5	13	attach	present	934:940	arg1	cells					960:964	the epithelial cells	945:964	the epithelial cells	945:964	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	0	14	from	horns	100:104	arg1	study					14:18	A preliminary study	0:18	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).	0:153	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	14	from	horns	100:104	arg1	Aepyceros					134:142	Aepyceros	134:142	Aepyceros	134:142	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	4	15	theme	uterine	733:739	arg1	horns					741:745	right and left uterine horns	718:745	right and left uterine horns in five of the specimens	718:770	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	16	contain	had	787:789	arg2	secretions					826:835	plentiful exocrine secretions	807:835	plentiful exocrine secretions	807:835	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	16	contain	had	787:789	arg1	sixth					781:785	sixth	781:785	sixth	781:785	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	16	contain	had	787:789	arg2	clefts					796:801	deep clefts	791:801	deep clefts	791:801	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	0	17	dep	Aepyceros	134:142	arg1	melampus					144:151	Aepyceros melampus	134:151	Aepyceros melampus	134:151	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	2	18	theme	lectins	466:472	arg1	system					505:510	an avidin-biotin revealing system	478:510	an avidin-biotin revealing system	478:510	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	2	18	theme	lectins	466:472	arg1	panel					454:458	a panel	452:458	a panel of 23 lectins	452:472	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	0	19	from	study	14:18	arg1	glycosylation					71:83	glycosylation	71:83	glycosylation	71:83	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	19	from	study	14:18	arg1	morphology					56:65	endometrial morphology	44:65	endometrial morphology	44:65	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	19	from	study	14:18	arg1	horns					100:104	the uterine horns	88:104	the uterine horns of the non-pregnant impala	88:131	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	4	20	theme	specimens	762:770	arg1	five					750:753	five	750:753	five	750:753	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	20	theme	specimens	762:770	arg1	specimens					762:770	the specimens	758:770	the specimens	758:770	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	7	21	theme	luminal	1148:1154	arg1	epithelium					1156:1165	luminal epithelium	1148:1165	luminal epithelium	1148:1165	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	5	22	theme	epithelial	949:958	arg1	cells					960:964	the epithelial cells	945:964	the epithelial cells	945:964	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	5	23	theme	supranuclear	907:918	arg1	granules					920:927	supranuclear granules	907:927	supranuclear granules	907:927	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	2	24	theme	revealing	495:503	arg1	system					505:510	an avidin-biotin revealing system	478:510	an avidin-biotin revealing system	478:510	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	10	25	theme	morphological	1566:1578	arg1	differences					1596:1606	morphological and biochemical differences	1566:1606	morphological and biochemical differences between right and left uterine horns in the impala	1566:1657	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	8	26	from	ovaries	1362:1368	arg1	similar					1379:1385	similar	1379:1385	similar	1379:1385	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	26	from	ovaries	1362:1368	arg1	present					1347:1353	present	1347:1353	present	1347:1353	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	26	from	ovaries	1362:1368	arg1	activities					1331:1340	The 3ßHSD and aromatase activities	1307:1340	activities	1331:1340	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	9	27	theme	corpus	1473:1478	arg1	haemorrhagicum					1480:1493	No corpus haemorrhagicum or corpus luteum	1470:1510	haemorrhagicum	1480:1493	No corpus haemorrhagicum or corpus luteum could be discerned.
30878391	7	28	theme	gland	1237:1241	arg1	epithelium					1243:1252	the gland epithelium	1233:1252	the gland epithelium	1233:1252	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	10	29	theme	further	1663:1669	arg1	studies					1671:1677	further studies	1663:1677	further studies	1663:1677	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	6	30	theme	progestagen	1021:1031	arg1	different					1050:1058	different	1050:1058	different	1050:1058	The serum progestagen was not markedly different, however, from that of the other specimens.
30878391	6	30	theme	progestagen	1021:1031	arg1	serum					1015:1019	The serum progestagen	1011:1031	The serum progestagen	1011:1031	The serum progestagen was not markedly different, however, from that of the other specimens.
30878391	10	31	theme	uterine	1767:1773	arg1	horn					1775:1778	one uterine horn	1763:1778	one uterine horn	1763:1778	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	2	32	theme	wild	383:386	arg1	non-pregnant					369:380	non-pregnant	369:380	non-pregnant	369:380	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	2	32	theme	wild	383:386	arg1	impala					388:393	wild impala	383:393	wild impala	383:393	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	5	33	theme	O-linked	993:1000	arg1	glycans					1002:1008	O-linked glycans	993:1008	O-linked glycans	993:1008	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	4	34	theme	exocrine	817:824	arg1	secretions					826:835	plentiful exocrine secretions	807:835	plentiful exocrine secretions	807:835	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	10	35	theme	uterine	1631:1637	arg1	horns					1639:1643	right and left uterine horns	1616:1643	right and left uterine horns	1616:1643	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	2	36	from	non-pregnant	369:380	arg1	horns					354:358	right and left uterine horns	331:358	right and left uterine horns from six non-pregnant, wild impala	331:393	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	6	37	theme	other	1087:1091	arg1	specimens					1093:1101	the other specimens	1083:1101	the other specimens	1083:1101	The serum progestagen was not markedly different, however, from that of the other specimens.
30878391	8	38	attach	present	1347:1353	arg2	activities					1331:1340	The 3ßHSD and aromatase activities	1307:1340	activities	1331:1340	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	38	attach	present	1347:1353	arg2	similar					1379:1385	similar	1379:1385	similar	1379:1385	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	38	attach	present	1347:1353	arg2	present					1347:1353	present	1347:1353	present	1347:1353	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	38	attach	present	1347:1353	arg1	ovaries					1362:1368	the ovaries	1358:1368	the ovaries	1358:1368	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	4	39	theme	deep	791:794	arg1	clefts					796:801	deep clefts	791:801	deep clefts	791:801	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	2	40	theme	uterine	346:352	arg1	horns					354:358	right and left uterine horns	331:358	right and left uterine horns from six non-pregnant, wild impala	331:393	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	8	41	from	present	1347:1353	arg1	ovaries					1362:1368	the ovaries	1358:1368	the ovaries	1358:1368	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	5	42	contain	had	973:975	arg2	classes					982:988	many classes	977:988	many classes of O-linked glycans	977:1008	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	5	42	contain	had	973:975	arg1	cells					960:964	the epithelial cells	945:964	the epithelial cells	945:964	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	10	43	theme	cyclical	1798:1805	arg1	changes					1815:1821	the cyclical hormone changes	1794:1821	the cyclical hormone changes which induce them	1794:1839	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	2	44	theme	possible	256:263	arg1	differences					265:275	possible differences	256:275	possible differences in morphology or glycosylation between the two horns	256:328	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	4	45	from	differences	666:676	arg1	glycosylation					696:708	glycosylation	696:708	glycosylation	696:708	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	45	from	differences	666:676	arg1	morphology					681:690	morphology	681:690	morphology	681:690	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	10	46	theme	biochemical	1584:1594	arg1	differences					1596:1606	morphological and biochemical differences	1566:1606	morphological and biochemical differences between right and left uterine horns in the impala	1566:1657	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	4	47	theme	few	651:653	arg1	differences					666:676	few detectable differences	651:676	few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens	651:770	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	3	48	theme	dehydrogenase	555:567	arg1	presence					517:524	The presence	513:524	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase	513:589	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	0	49	theme	non-pregnant	113:124	arg1	impala					126:131	the non-pregnant impala	109:131	the non-pregnant impala	109:131	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	1	50	dep	commences	168:176	arg1	Aepyceros					220:228	Aepyceros	220:228	Aepyceros	220:228	Placentation commences only in the right uterine horn in impala (Aepyceros melampus).
30878391	3	51	theme	3ß	537:538	arg1	3ßHSD					570:574	3ßHSD	570:574	3ßHSD	570:574	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	3	51	theme	3ß	537:538	arg1	dehydrogenase					555:567	ovarian 3ß hydroxysteroid dehydrogenase	529:567	ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD)	529:575	The presence of ovarian 3ß hydroxysteroid dehydrogenase (3ßHSD) and aromatase was also investigated using immunocytochemistry.
30878391	5	52	gly	glycosylated	882:893	arg1	clusters					895:902	Heavily glycosylated clusters	874:902	Heavily glycosylated clusters of supranuclear granules	874:927	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	7	53	theme	these	1300:1304	arg1	these					1300:1304	these	1300:1304	these	1300:1304	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	7	53	theme	these	1300:1304	arg1	four					1292:1295	four	1292:1295	four	1292:1295	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	1	54	theme	uterine	196:202	arg1	horn					204:207	the right uterine horn	186:207	the right uterine horn	186:207	Placentation commences only in the right uterine horn in impala (Aepyceros melampus).
30878391	8	55	from	similar	1379:1385	arg1	impala					1390:1395	impala	1390:1395	impala with or without progestagen concentrations >1 ng/ml in peripheral blood	1390:1467	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	10	56	theme	other	1709:1713	arg1	species					1715:1721	other species	1709:1721	other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them	1709:1839	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	5	57	theme	glycosylated	882:893	arg1	clusters					895:902	Heavily glycosylated clusters	874:902	Heavily glycosylated clusters of supranuclear granules	874:927	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	5	58	link	O-linked	993:1000	arg1	glycans					1002:1008	O-linked glycans	993:1008	O-linked glycans	993:1008	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	4	59	theme	right	718:722	arg1	horns					741:745	right and left uterine horns	718:745	right and left uterine horns in five of the specimens	718:770	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	60	from	clefts	796:801	arg1	left					868:871	left	868:871	left	868:871	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	60	from	clefts	796:801	arg1	horn					850:853	the right horn	840:853	the right horn	840:853	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	8	61	located	present	1347:1353	arg2	activities					1331:1340	The 3ßHSD and aromatase activities	1307:1340	activities	1331:1340	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	61	located	present	1347:1353	arg2	similar					1379:1385	similar	1379:1385	similar	1379:1385	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	61	located	present	1347:1353	arg2	present					1347:1353	present	1347:1353	present	1347:1353	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	61	located	present	1347:1353	arg1	ovaries					1362:1368	the ovaries	1358:1368	the ovaries	1358:1368	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	4	62	theme	left	728:731	arg1	horns					741:745	right and left uterine horns	718:745	right and left uterine horns in five of the specimens	718:770	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	2	63	from	differences	265:275	arg1	glycosylation					294:306	glycosylation	294:306	glycosylation	294:306	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	2	63	from	differences	265:275	arg1	morphology					280:289	morphology	280:289	morphology	280:289	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	7	64	theme	epithelium	1156:1165	arg1	greater					1171:1177	greater	1171:1177	greater	1171:1177	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	7	64	theme	epithelium	1156:1165	arg1	height					1138:1143	the height	1134:1143	the height of luminal epithelium	1134:1165	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	0	65	theme	uterine	92:98	arg1	horns					100:104	the uterine horns	88:104	the uterine horns of the non-pregnant impala	88:131	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	8	66	theme	progestagen	1413:1423	arg1	concentrations					1425:1438	progestagen concentrations	1413:1438	progestagen concentrations >1 ng/ml in peripheral blood	1413:1467	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	10	67	theme	right	1616:1620	arg1	horns					1639:1643	right and left uterine horns	1616:1643	right and left uterine horns	1616:1643	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	7	68	theme	epithelium	1243:1252	arg1	height					1223:1228	the height	1219:1228	the height of the gland epithelium	1219:1252	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	7	68	theme	epithelium	1243:1252	arg1	greater					1263:1269	greater	1263:1269	greater	1263:1269	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	2	69	theme	avidin-biotin	481:493	arg1	system					505:510	an avidin-biotin revealing system	478:510	an avidin-biotin revealing system	478:510	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	0	70	from	heterogeneity	27:39	arg1	glycosylation					71:83	glycosylation	71:83	glycosylation	71:83	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	70	from	heterogeneity	27:39	arg1	morphology					56:65	endometrial morphology	44:65	endometrial morphology	44:65	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	70	from	heterogeneity	27:39	arg1	horns					100:104	the uterine horns	88:104	the uterine horns of the non-pregnant impala	88:131	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	71	theme	preliminary	2:12	arg1	study					14:18	A preliminary study	0:18	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).	0:153	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	71	theme	preliminary	2:12	arg1	Aepyceros					134:142	Aepyceros	134:142	Aepyceros	134:142	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	4	72	from	secretions	826:835	arg1	left					868:871	left	868:871	left	868:871	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	72	from	secretions	826:835	arg1	horn					850:853	the right horn	840:853	the right horn	840:853	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	5	73	theme	granules	920:927	arg1	clusters					895:902	Heavily glycosylated clusters	874:902	Heavily glycosylated clusters of supranuclear granules	874:927	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	8	74	theme	peripheral	1452:1461	arg1	blood					1463:1467	peripheral blood	1452:1467	peripheral blood	1452:1467	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	0	75	from	glycosylation	71:83	arg1	study					14:18	A preliminary study	0:18	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).	0:153	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	75	from	glycosylation	71:83	arg1	Aepyceros					134:142	Aepyceros	134:142	Aepyceros	134:142	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	8	76	from	impala	1390:1395	arg1	activities					1331:1340	The 3ßHSD and aromatase activities	1307:1340	activities	1331:1340	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	76	from	impala	1390:1395	arg1	present					1347:1353	present	1347:1353	present	1347:1353	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	76	from	impala	1390:1395	arg1	similar					1379:1385	similar	1379:1385	similar	1379:1385	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	4	77	from	horns	741:745	arg1	five					750:753	five	750:753	five	750:753	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	4	77	from	horns	741:745	arg1	specimens					762:770	the specimens	758:770	the specimens	758:770	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	0	78	theme	heterogeneity	27:39	arg1	study					14:18	A preliminary study	0:18	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).	0:153	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	0	78	theme	heterogeneity	27:39	arg1	Aepyceros					134:142	Aepyceros	134:142	Aepyceros	134:142	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	9	79	theme	corpus	1498:1503	arg1	luteum					1505:1510	No corpus haemorrhagicum or corpus luteum	1470:1510	luteum	1505:1510	No corpus haemorrhagicum or corpus luteum could be discerned.
30878391	0	80	theme	endometrial	44:54	arg1	morphology					56:65	endometrial morphology	44:65	endometrial morphology	44:65	A preliminary study of the heterogeneity in endometrial morphology and glycosylation in the uterine horns of the non-pregnant impala (Aepyceros melampus).
30878391	5	81	theme	glycans	1002:1008	arg1	classes					982:988	many classes	977:988	many classes of O-linked glycans	977:1008	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	4	82	theme	plentiful	807:815	arg1	secretions					826:835	plentiful exocrine secretions	807:835	plentiful exocrine secretions	807:835	There were few detectable differences in morphology and glycosylation between right and left uterine horns in five of the specimens, but the sixth had deep clefts and plentiful exocrine secretions in the right horn, and not the left.
30878391	10	83	theme	left	1626:1629	arg1	horns					1639:1643	right and left uterine horns	1616:1643	right and left uterine horns	1616:1643	These findings indicate there are morphological and biochemical differences between right and left uterine horns in the impala and further studies are needed on both impala and other species in which placentation commences only in one uterine horn, to establish the cyclical hormone changes which induce them.
30878391	5	84	from	present	934:940	arg1	cells					960:964	the epithelial cells	945:964	the epithelial cells	945:964	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	5	85	located	present	934:940	arg2	clusters					895:902	Heavily glycosylated clusters	874:902	Heavily glycosylated clusters of supranuclear granules	874:927	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	5	85	located	present	934:940	arg1	cells					960:964	the epithelial cells	945:964	the epithelial cells	945:964	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	8	86	theme	3ßHSD	1311:1315	arg1	similar					1379:1385	similar	1379:1385	similar	1379:1385	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	86	theme	3ßHSD	1311:1315	arg1	present					1347:1353	present	1347:1353	present	1347:1353	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	86	theme	3ßHSD	1311:1315	arg1	activities					1331:1340	The 3ßHSD and aromatase activities	1307:1340	activities	1331:1340	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	2	87	theme	left	341:344	arg1	horns					354:358	right and left uterine horns	331:358	right and left uterine horns from six non-pregnant, wild impala	331:393	To investigate possible differences in morphology or glycosylation between the two horns, right and left uterine horns from six non-pregnant, wild impala were examined morphometrically and histochemically using a panel of 23 lectins and an avidin-biotin revealing system.
30878391	5	88	theme	many	977:980	arg1	classes					982:988	many classes	977:988	many classes of O-linked glycans	977:1008	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30878391	8	89	theme	aromatase	1321:1329	arg1	similar					1379:1385	similar	1379:1385	similar	1379:1385	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	89	theme	aromatase	1321:1329	arg1	present					1347:1353	present	1347:1353	present	1347:1353	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	8	89	theme	aromatase	1321:1329	arg1	activities					1331:1340	The 3ßHSD and aromatase activities	1307:1340	activities	1331:1340	The 3ßHSD and aromatase activities were present in the ovaries and were similar in impala with or without progestagen concentrations >1 ng/ml in peripheral blood.
30878391	6	90	from	that	1075:1078	arg1	different					1050:1058	different	1050:1058	different	1050:1058	The serum progestagen was not markedly different, however, from that of the other specimens.
30878391	6	90	from	that	1075:1078	arg1	serum					1015:1019	The serum progestagen	1011:1031	The serum progestagen	1011:1031	The serum progestagen was not markedly different, however, from that of the other specimens.
30878391	7	91	theme	specimens	1123:1131	arg1	five					1107:1110	five	1107:1110	five	1107:1110	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	7	91	theme	specimens	1123:1131	arg1	specimens					1123:1131	the six specimens	1115:1131	the six specimens	1115:1131	In five of the six specimens, the height of luminal epithelium was greater on the right than that on the left, and the height of the gland epithelium was also greater on the right side in four of these.
30878391	5	92	from	cells	960:964	arg1	present					934:940	present	934:940	present	934:940	Heavily glycosylated clusters of supranuclear granules were present in the epithelial cells, which had many classes of O-linked glycans.
30591584	4	0	from	biosynthesis	732:743	arg1	activity					850:857	nuclear polypeptide GalNAc -transferase activity	810:857	nuclear polypeptide GalNAc -transferase activity	810:857	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	0	from	biosynthesis	732:743	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	0	from	biosynthesis	732:743	arg1	substrate					786:794	the donor substrate	776:794	the donor substrate (UDP-GalNAc)	776:807	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	0	from	biosynthesis	732:743	arg1	transferase					873:883	a GalNAc transferase	864:883	a GalNAc transferase (polypeptide GalNAc-T3)	864:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	3	1	theme	proteins	476:483	arg1	PTM					461:463	a novel PTM	453:463	a novel PTM of nuclear proteins in the nucleus of human cells	453:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	3	2	from	proteins	476:483	arg1	nucleus					492:498	the nucleus	488:498	the nucleus of human cells	488:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	2	3	link	O-linked	249:256	arg1	glycosylation					258:270	O-linked glycosylation	249:270	O-linked glycosylation (O-GalNAc)	249:281	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	2	3	link	O-linked	249:256	arg1	O-GalNAc					273:280	O-GalNAc	273:280	O-GalNAc	273:280	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	4	4	theme	polypeptide	886:896	arg1	GalNAc-T3					898:906	polypeptide GalNAc-T3	886:906	polypeptide GalNAc-T3	886:906	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	4	theme	polypeptide	886:896	arg1	transferase					873:883	a GalNAc transferase	864:883	a GalNAc transferase (polypeptide GalNAc-T3)	864:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	0	5	from	Biosynthesis	0:11	arg1	nucleus					66:72	the human cell nucleus	51:72	the human cell nucleus	51:72	Biosynthesis of O-N-acetylgalactosamine glycans in the human cell nucleus.
30591584	4	6	theme	polypeptide	818:828	arg1	activity					850:857	nuclear polypeptide GalNAc -transferase activity	810:857	nuclear polypeptide GalNAc -transferase activity	810:857	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	6	theme	polypeptide	818:828	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	3	7	theme	cells	509:513	arg1	nucleus					492:498	the nucleus	488:498	the nucleus of human cells	488:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	6	8	theme	proteins	1111:1118	arg1	glycosylation					1086:1098	O-GalNAc glycosylation	1077:1098	O-GalNAc glycosylation of nuclear proteins in mammalian cells	1077:1137	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	4	9	theme	nuclear	810:816	arg1	activity					850:857	nuclear polypeptide GalNAc -transferase activity	810:857	nuclear polypeptide GalNAc -transferase activity	810:857	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	9	theme	nuclear	810:816	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	10	theme	FRET	678:681	arg1	analyses					683:690	FRET analyses	678:690	FRET analyses	678:690	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	10	theme	FRET	678:681	arg1	fractions					570:578	soluble nuclear fractions	554:578	soluble nuclear fractions from purified nuclei	554:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	6	11	from	cells	1133:1137	arg1	demonstration					1060:1072	The demonstration	1056:1072	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here	1056:1151	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	3	12	from	nucleus	492:498	arg1	PTM					461:463	a novel PTM	453:463	a novel PTM of nuclear proteins in the nucleus of human cells	453:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	1	13	theme	Biological	75:84	arg1	functions					86:94	Biological functions	75:94	Biological functions of nuclear proteins	75:114	Biological functions of nuclear proteins are regulated by post-translational modifications (PTMs) that modulate gene expression and cellular physiology.
30591584	3	14	from	emphasis	524:531	arg1	cells					541:545	HeLa cells	536:545	HeLa cells	536:545	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	3	15	theme	O-GalNAc	410:417	arg1	biosynthesis					426:437	O-GalNAc glycan biosynthesis	410:437	O-GalNAc glycan biosynthesis	410:437	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	5	16	gly	glycosylated	943:954	arg1	proteins					956:963	O-GalNAc glycosylated proteins	934:963	O-GalNAc glycosylated proteins	934:963	Moreover, we identified O-GalNAc glycosylated proteins in the nucleus and present solid evidence for O-GalNAc glycan synthesis in this organelle.
30591584	4	17	theme	donor	780:784	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	17	theme	donor	780:784	arg1	UDP-GalNAc					797:806	UDP-GalNAc	797:806	UDP-GalNAc	797:806	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	17	theme	donor	780:784	arg1	substrate					786:794	the donor substrate	776:794	the donor substrate (UDP-GalNAc)	776:807	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	6	18	theme	nuclear	1103:1109	arg1	proteins					1111:1118	nuclear proteins	1103:1118	nuclear proteins	1103:1118	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	3	19	theme	human	503:507	arg1	cells					509:513	human cells	503:513	human cells	503:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	1	20	theme	gene	187:190	arg1	expression					192:201	gene expression	187:201	gene expression	187:201	Biological functions of nuclear proteins are regulated by post-translational modifications (PTMs) that modulate gene expression and cellular physiology.
30591584	3	21	from	PTM	461:463	arg1	nucleus					492:498	the nucleus	488:498	the nucleus of human cells	488:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	4	22	theme	GalNAc	830:835	arg1	activity					850:857	nuclear polypeptide GalNAc -transferase activity	810:857	nuclear polypeptide GalNAc -transferase activity	810:857	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	22	theme	GalNAc	830:835	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	6	23	theme	important	1157:1165	arg1	implications					1167:1178	important implications	1157:1178	important implications for cell and chemical biology	1157:1208	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	2	24	theme	proteins	303:310	arg1	PTM					288:290	a PTM	286:290	a PTM of nuclear proteins in the human cell	286:328	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	4	25	theme	fluorescence	620:631	arg1	fractions					570:578	soluble nuclear fractions	554:578	soluble nuclear fractions from purified nuclei	554:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	25	theme	fluorescence	620:631	arg1	microscopy					633:642	fluorescence microscopy	620:642	fluorescence microscopy	620:642	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	0	26	theme	glycans	40:46	arg1	Biosynthesis					0:11	Biosynthesis	0:11	Biosynthesis of O-N-acetylgalactosamine glycans in the human cell nucleus	0:72	Biosynthesis of O-N-acetylgalactosamine glycans in the human cell nucleus.
30591584	4	27	theme	glycans	757:763	arg1	biosynthesis					732:743	biosynthesis	732:743	biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	732:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	5	28	theme	glycosylated	943:954	arg1	proteins					956:963	O-GalNAc glycosylated proteins	934:963	O-GalNAc glycosylated proteins	934:963	Moreover, we identified O-GalNAc glycosylated proteins in the nucleus and present solid evidence for O-GalNAc glycan synthesis in this organelle.
30591584	2	29	theme	nuclear	295:301	arg1	proteins					303:310	nuclear proteins	295:310	nuclear proteins	295:310	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	1	30	theme	cellular	207:214	arg1	physiology					216:225	cellular physiology	207:225	cellular physiology	207:225	Biological functions of nuclear proteins are regulated by post-translational modifications (PTMs) that modulate gene expression and cellular physiology.
30591584	1	31	theme	nuclear	99:105	arg1	proteins					107:114	nuclear proteins	99:114	nuclear proteins	99:114	Biological functions of nuclear proteins are regulated by post-translational modifications (PTMs) that modulate gene expression and cellular physiology.
30591584	5	32	theme	O-GalNAc	1011:1018	arg1	synthesis					1027:1035	O-GalNAc glycan synthesis	1011:1035	O-GalNAc glycan synthesis in this organelle	1011:1053	Moreover, we identified O-GalNAc glycosylated proteins in the nucleus and present solid evidence for O-GalNAc glycan synthesis in this organelle.
30591584	4	33	from	nuclei	594:599	arg1	chromatography					654:667	affinity chromatography	645:667	affinity chromatography	645:667	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	33	from	nuclei	594:599	arg1	analyses					683:690	FRET analyses	678:690	FRET analyses	678:690	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	33	from	nuclei	594:599	arg1	fractions					570:578	soluble nuclear fractions	554:578	soluble nuclear fractions from purified nuclei	554:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	33	from	nuclei	594:599	arg1	assays					612:617	enzymatic assays	602:617	enzymatic assays	602:617	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	33	from	nuclei	594:599	arg1	MS					670:671	MS	670:671	MS	670:671	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	33	from	nuclei	594:599	arg1	microscopy					633:642	fluorescence microscopy	620:642	fluorescence microscopy	620:642	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	34	theme	purified	585:592	arg1	nuclei					594:599	purified nuclei	585:599	purified nuclei	585:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	6	35	theme	O-GalNAc	1077:1084	arg1	glycosylation					1086:1098	O-GalNAc glycosylation	1077:1098	O-GalNAc glycosylation of nuclear proteins in mammalian cells	1077:1137	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	4	36	theme	enzymatic	602:610	arg1	fractions					570:578	soluble nuclear fractions	554:578	soluble nuclear fractions from purified nuclei	554:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	36	theme	enzymatic	602:610	arg1	assays					612:617	enzymatic assays	602:617	enzymatic assays	602:617	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	3	37	theme	biosynthesis	426:437	arg1	initiation					396:405	the initiation	392:405	the initiation of O-GalNAc glycan biosynthesis	392:437	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	0	38	theme	O-N-acetylgalactosamine	16:38	arg1	glycans					40:46	O-N-acetylgalactosamine glycans	16:46	O-N-acetylgalactosamine glycans	16:46	Biosynthesis of O-N-acetylgalactosamine glycans in the human cell nucleus.
30591584	6	39	contain	has	1153:1155	arg1	demonstration					1060:1072	The demonstration	1056:1072	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here	1056:1151	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	6	39	contain	has	1153:1155	arg2	implications					1167:1178	important implications	1157:1178	important implications for cell and chemical biology	1157:1208	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	4	40	theme	GalNAc	866:871	arg1	GalNAc-T3					898:906	polypeptide GalNAc-T3	886:906	polypeptide GalNAc-T3	886:906	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	40	theme	GalNAc	866:871	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	40	theme	GalNAc	866:871	arg1	transferase					873:883	a GalNAc transferase	864:883	a GalNAc transferase (polypeptide GalNAc-T3)	864:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	6	41	theme	chemical	1193:1200	arg1	biology					1202:1208	chemical biology	1193:1208	chemical biology	1193:1208	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	0	42	theme	cell	61:64	arg1	nucleus					66:72	the human cell nucleus	51:72	the human cell nucleus	51:72	Biosynthesis of O-N-acetylgalactosamine glycans in the human cell nucleus.
30591584	5	43	from	synthesis	1027:1035	arg1	organelle					1045:1053	this organelle	1040:1053	this organelle	1040:1053	Moreover, we identified O-GalNAc glycosylated proteins in the nucleus and present solid evidence for O-GalNAc glycan synthesis in this organelle.
30591584	4	44	theme	-transferase	837:848	arg1	activity					850:857	nuclear polypeptide GalNAc -transferase activity	810:857	nuclear polypeptide GalNAc -transferase activity	810:857	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	44	theme	-transferase	837:848	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	3	45	theme	HeLa	536:539	arg1	cells					541:545	HeLa cells	536:545	HeLa cells	536:545	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	6	46	from	demonstration	1060:1072	arg1	cells					1133:1137	mammalian cells	1123:1137	mammalian cells	1123:1137	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	6	47	theme	glycosylation	1086:1098	arg1	demonstration					1060:1072	The demonstration	1056:1072	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here	1056:1151	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	0	48	theme	human	55:59	arg1	nucleus					66:72	the human cell nucleus	51:72	the human cell nucleus	51:72	Biosynthesis of O-N-acetylgalactosamine glycans in the human cell nucleus.
30591584	3	49	theme	novel	455:459	arg1	PTM					461:463	a novel PTM	453:463	a novel PTM of nuclear proteins in the nucleus of human cells	453:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	6	50	gly	glycosylation	1086:1098	arg1	proteins					1111:1118	nuclear proteins	1103:1118	nuclear proteins	1103:1118	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	6	50	gly	glycosylation	1086:1098	arg1	cells					1133:1137	mammalian cells	1123:1137	mammalian cells	1123:1137	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	6	51	from	glycosylation	1086:1098	arg1	cells					1133:1137	mammalian cells	1123:1137	mammalian cells	1123:1137	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	3	52	theme	nuclear	468:474	arg1	proteins					476:483	nuclear proteins	468:483	nuclear proteins in the nucleus of human cells	468:513	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	4	53	theme	O-GalNAc	748:755	arg1	glycans					757:763	O-GalNAc glycans	748:763	O-GalNAc glycans	748:763	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	5	54	theme	solid	992:996	arg1	evidence					998:1005	solid evidence	992:1005	solid evidence for O-GalNAc glycan synthesis in this organelle	992:1053	Moreover, we identified O-GalNAc glycosylated proteins in the nucleus and present solid evidence for O-GalNAc glycan synthesis in this organelle.
30591584	1	55	theme	post-translational	133:150	arg1	PTMs					167:170	PTMs	167:170	PTMs	167:170	Biological functions of nuclear proteins are regulated by post-translational modifications (PTMs) that modulate gene expression and cellular physiology.
30591584	1	55	theme	post-translational	133:150	arg1	modifications					152:164	post-translational modifications	133:164	post-translational modifications (PTMs) that modulate gene expression and cellular physiology	133:225	Biological functions of nuclear proteins are regulated by post-translational modifications (PTMs) that modulate gene expression and cellular physiology.
30591584	1	56	theme	proteins	107:114	arg1	functions					86:94	Biological functions	75:94	Biological functions of nuclear proteins	75:114	Biological functions of nuclear proteins are regulated by post-translational modifications (PTMs) that modulate gene expression and cellular physiology.
30591584	4	57	theme	nuclear	562:568	arg1	chromatography					654:667	affinity chromatography	645:667	affinity chromatography	645:667	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	57	theme	nuclear	562:568	arg1	analyses					683:690	FRET analyses	678:690	FRET analyses	678:690	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	57	theme	nuclear	562:568	arg1	fractions					570:578	soluble nuclear fractions	554:578	soluble nuclear fractions from purified nuclei	554:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	57	theme	nuclear	562:568	arg1	assays					612:617	enzymatic assays	602:617	enzymatic assays	602:617	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	57	theme	nuclear	562:568	arg1	MS					670:671	MS	670:671	MS	670:671	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	57	theme	nuclear	562:568	arg1	microscopy					633:642	fluorescence microscopy	620:642	fluorescence microscopy	620:642	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	6	58	theme	mammalian	1123:1131	arg1	cells					1133:1137	mammalian cells	1123:1137	mammalian cells	1123:1137	The demonstration of O-GalNAc glycosylation of nuclear proteins in mammalian cells reported here has important implications for cell and chemical biology.
30591584	5	59	theme	glycan	1020:1025	arg1	synthesis					1027:1035	O-GalNAc glycan synthesis	1011:1035	O-GalNAc glycan synthesis in this organelle	1011:1053	Moreover, we identified O-GalNAc glycosylated proteins in the nucleus and present solid evidence for O-GalNAc glycan synthesis in this organelle.
30591584	2	60	from	PTM	288:290	arg1	cell					325:328	the human cell	315:328	the human cell	315:328	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	2	61	theme	human	319:323	arg1	cell					325:328	the human cell	315:328	the human cell	315:328	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	2	62	theme	glycosylation	258:270	arg1	role					241:244	the role	237:244	the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell	237:328	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	5	63	dep	glycosylated	943:954	arg1	O-GalNAc					934:941	O-GalNAc	934:941	O-GalNAc	934:941	Moreover, we identified O-GalNAc glycosylated proteins in the nucleus and present solid evidence for O-GalNAc glycan synthesis in this organelle.
30591584	4	64	theme	affinity	645:652	arg1	chromatography					654:667	affinity chromatography	645:667	affinity chromatography	645:667	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	64	theme	affinity	645:652	arg1	fractions					570:578	soluble nuclear fractions	554:578	soluble nuclear fractions from purified nuclei	554:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	3	65	theme	glycan	419:424	arg1	biosynthesis					426:437	O-GalNAc glycan biosynthesis	410:437	O-GalNAc glycan biosynthesis	410:437	Here, we examined in detail the initiation of O-GalNAc glycan biosynthesis, representing a novel PTM of nuclear proteins in the nucleus of human cells, with an emphasis on HeLa cells.
30591584	4	66	dep	nuclei	768:773	arg1	substrate					786:794	the donor substrate	776:794	the donor substrate (UDP-GalNAc)	776:807	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	66	dep	nuclei	768:773	arg1	transferase					873:883	a GalNAc transferase	864:883	a GalNAc transferase (polypeptide GalNAc-T3)	864:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	66	dep	nuclei	768:773	arg1	UDP-GalNAc					797:806	UDP-GalNAc	797:806	UDP-GalNAc	797:806	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	66	dep	nuclei	768:773	arg1	activity					850:857	nuclear polypeptide GalNAc -transferase activity	810:857	nuclear polypeptide GalNAc -transferase activity	810:857	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	66	dep	nuclei	768:773	arg1	nuclei					768:773	nuclei	768:773	nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3)	768:907	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	66	dep	nuclei	768:773	arg1	GalNAc-T3					898:906	polypeptide GalNAc-T3	886:906	polypeptide GalNAc-T3	886:906	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	2	67	theme	O-linked	249:256	arg1	glycosylation					258:270	O-linked glycosylation	249:270	O-linked glycosylation (O-GalNAc)	249:281	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	2	67	theme	O-linked	249:256	arg1	O-GalNAc					273:280	O-GalNAc	273:280	O-GalNAc	273:280	However, the role of O-linked glycosylation (O-GalNAc) as a PTM of nuclear proteins in the human cell has not been previously reported.
30591584	4	68	theme	soluble	554:560	arg1	chromatography					654:667	affinity chromatography	645:667	affinity chromatography	645:667	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	68	theme	soluble	554:560	arg1	analyses					683:690	FRET analyses	678:690	FRET analyses	678:690	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	68	theme	soluble	554:560	arg1	fractions					570:578	soluble nuclear fractions	554:578	soluble nuclear fractions from purified nuclei	554:599	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	68	theme	soluble	554:560	arg1	assays					612:617	enzymatic assays	602:617	enzymatic assays	602:617	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	68	theme	soluble	554:560	arg1	MS					670:671	MS	670:671	MS	670:671	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30591584	4	68	theme	soluble	554:560	arg1	microscopy					633:642	fluorescence microscopy	620:642	fluorescence microscopy	620:642	Using soluble nuclear fractions from purified nuclei, enzymatic assays, fluorescence microscopy, affinity chromatography, MS, and FRET analyses, we identified all factors required for biosynthesis of O-GalNAc glycans in nuclei: the donor substrate (UDP-GalNAc), nuclear polypeptide GalNAc -transferase activity, and a GalNAc transferase (polypeptide GalNAc-T3).
30123425	0	0	theme	early	97:101	arg1	adenocarcinoma					114:127	early stage lung adenocarcinoma	97:127	early stage lung adenocarcinoma	97:127	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	8	1	theme	stage	1335:1339	arg1	patients					1343:1350	stage I patients	1335:1350	stage I patients	1335:1350	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	7	2	with	patients	1081:1088	arg1	tumors					1110:1115	EGFR wild-type tumors	1095:1115	EGFR wild-type tumors at variable stages (P=0.038)	1095:1144	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	3	3	attach	attachment	376:385	arg1	serine					426:431	serine	426:431	serine	426:431	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	3	3	attach	attachment	376:385	arg2	O-GlcNAc					413:420	O-GlcNAc	413:420	O-GlcNAc	413:420	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	3	3	attach	attachment	376:385	arg2	β-N-acetylglucosamine					390:410	β-N-acetylglucosamine	390:410	β-N-acetylglucosamine (O-GlcNAc)	390:421	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	3	3	attach	attachment	376:385	arg1	threonine					436:444	threonine	436:444	threonine	436:444	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	5	4	theme	OGT	710:712	arg1	utility					699:705	the utility	695:705	the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma	695:779	We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma.
30123425	8	5	theme	OGT	1184:1186	arg1	factor					1228:1233	an independent prognostic factor	1202:1233	an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients	1202:1350	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	8	5	theme	OGT	1184:1186	arg1	expression					1188:1197	OGT expression	1184:1197	OGT expression	1184:1197	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	1	6	theme	appropriate	177:187	arg1	interventions					189:201	appropriate interventions	177:201	appropriate interventions	177:201	Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge.
30123425	0	7	theme	lung	109:112	arg1	adenocarcinoma					114:127	early stage lung adenocarcinoma	97:127	early stage lung adenocarcinoma	97:127	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	6	8	theme	variable	910:917	arg1	stages					919:924	variable stages	910:924	variable stages of disease (P=0.029)	910:945	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	3	9	dep	serine	426:431	arg1	residues					446:453	residues	446:453	residues	446:453	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	0	10	link	O-linked	5:12	arg1	transferase					34:44	O-linked N-acetylglucosamine transferase	5:44	High O-linked N-acetylglucosamine transferase expression	0:55	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	8	11	from	OS	1288:1289	arg1	patients					1343:1350	stage I patients	1335:1350	stage I patients	1335:1350	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	0	12	theme	stage	103:107	arg1	adenocarcinoma					114:127	early stage lung adenocarcinoma	97:127	early stage lung adenocarcinoma	97:127	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	0	13	from	survival	71:78	arg1	patients					83:90	patients	83:90	patients with early stage lung adenocarcinoma	83:127	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	5	14	theme	OGA	715:717	arg1	utility					699:705	the utility	695:705	the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma	695:779	We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma.
30123425	0	15	with	patients	83:90	arg1	adenocarcinoma					114:127	early stage lung adenocarcinoma	97:127	early stage lung adenocarcinoma	97:127	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	8	16	dep	RFS	1239:1241	arg1	HR					1244:1245	HR 2.946	1244:1251	HR 2.946	1244:1251	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	7	17	theme	poorer	1068:1073	arg1	OS					1075:1076	poorer OS	1068:1076	poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038)	1068:1144	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	6	18	theme	overall	840:846	arg1	survival					848:855	poor overall survival	835:855	poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029)	835:945	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	18	theme	overall	840:846	arg1	OS					858:859	OS	858:859	OS	858:859	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	8	19	theme	I	1341:1341	arg1	patients					1343:1350	stage I patients	1335:1350	stage I patients	1335:1350	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	3	20	theme	proteins	472:479	arg1	serine					426:431	serine	426:431	serine	426:431	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	3	20	theme	proteins	472:479	arg1	threonine					436:444	threonine	436:444	threonine	436:444	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	1	21	theme	interventions	189:201	arg1	selection					164:172	selection	164:172	selection of appropriate interventions to lung cancer a challenge	164:228	Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge.
30123425	3	22	theme	β-N-acetylglucosamine	390:410	arg1	O-GlcNAcylation					355:369	O-GlcNAcylation	355:369	O-GlcNAcylation	355:369	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	3	22	theme	β-N-acetylglucosamine	390:410	arg1	attachment					376:385	the attachment	372:385	the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins	372:479	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	6	23	from	survival	978:985	arg1	P=0.035					1014:1020	P=0.035	1014:1020	P=0.035	1014:1020	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	23	from	survival	978:985	arg1	patients					1004:1011	stage I patients	996:1011	stage I patients (P=0.035)	996:1021	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	24	theme	poor	835:838	arg1	survival					848:855	poor overall survival	835:855	poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029)	835:945	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	24	theme	poor	835:838	arg1	OS					858:859	OS	858:859	OS	858:859	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	9	25	theme	lung	1440:1443	arg1	adenocarcinomas					1445:1459	early stage lung adenocarcinomas	1428:1459	early stage lung adenocarcinomas	1428:1459	Our findings indicate OGT is a promising biomarker for further classifying early stage lung adenocarcinomas.
30123425	3	26	theme	protein	492:498	arg1	functions					500:508	protein functions	492:508	protein functions	492:508	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	0	27	theme	O-linked	5:12	arg1	transferase					34:44	O-linked N-acetylglucosamine transferase	5:44	High O-linked N-acetylglucosamine transferase expression	0:55	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	7	28	from	stages	1129:1134	arg1	tumors					1110:1115	EGFR wild-type tumors	1095:1115	EGFR wild-type tumors at variable stages (P=0.038)	1095:1144	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	1	29	theme	lung	206:209	arg1	cancer					211:216	lung cancer a challenge	206:228	lung cancer a challenge	206:228	Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge.
30123425	0	30	theme	High	0:3	arg1	expression					46:55	High O-linked N-acetylglucosamine transferase expression	0:55	High O-linked N-acetylglucosamine transferase expression	0:55	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	6	31	theme	recurrence-free	962:976	arg1	RFS					988:990	RFS	988:990	RFS	988:990	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	31	theme	recurrence-free	962:976	arg1	survival					978:985	poor recurrence-free survival	957:985	poor recurrence-free survival (RFS) in stage I patients (P=0.035)	957:1021	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	7	32	theme	OGT	1029:1031	arg1	expression					1033:1042	High OGT expression	1024:1042	High OGT expression	1024:1042	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	6	33	theme	stage	870:874	arg1	patients					878:885	stage I patients	870:885	stage I patients (P=0.032)	870:895	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	33	theme	stage	870:874	arg1	P=0.032					888:894	P=0.032	888:894	P=0.032	888:894	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	8	34	theme	independent	1205:1215	arg1	factor					1228:1233	an independent prognostic factor	1202:1233	an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients	1202:1350	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	8	34	theme	independent	1205:1215	arg1	expression					1188:1197	OGT expression	1184:1197	OGT expression	1184:1197	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	0	35	theme	transferase	34:44	arg1	expression					46:55	High O-linked N-acetylglucosamine transferase expression	0:55	High O-linked N-acetylglucosamine transferase expression	0:55	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	6	36	theme	poor	957:960	arg1	RFS					988:990	RFS	988:990	RFS	988:990	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	36	theme	poor	957:960	arg1	survival					978:985	poor recurrence-free survival	957:985	poor recurrence-free survival (RFS) in stage I patients (P=0.035)	957:1021	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	5	37	theme	potential	736:744	arg1	biomarkers					746:755	potential biomarkers	736:755	potential biomarkers for lung adenocarcinoma	736:779	We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma.
30123425	2	38	theme	treatment	333:341	arg1	strategies					343:352	personalized treatment strategies	320:352	personalized treatment strategies	320:352	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	5	39	used	used	658:661	arg2	We					655:656	We	655:656	We	655:656	We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma.
30123425	0	40	theme	N-acetylglucosamine	14:32	arg1	transferase					34:44	O-linked N-acetylglucosamine transferase	5:44	High O-linked N-acetylglucosamine transferase expression	0:55	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	9	41	theme	stage	1434:1438	arg1	adenocarcinomas					1445:1459	early stage lung adenocarcinomas	1428:1459	early stage lung adenocarcinomas	1428:1459	Our findings indicate OGT is a promising biomarker for further classifying early stage lung adenocarcinomas.
30123425	2	42	theme	personalized	320:331	arg1	strategies					343:352	personalized treatment strategies	320:352	personalized treatment strategies	320:352	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	4	43	theme	O-GlcNAc	610:617	arg1	addition					619:626	O-GlcNAc addition	610:626	O-GlcNAc addition	610:626	O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA) catalyze O-GlcNAc addition and removal, respectively.
30123425	7	44	theme	High	1024:1027	arg1	expression					1033:1042	High OGT expression	1024:1042	High OGT expression	1024:1042	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	2	45	theme	disease	262:268	arg1	risk					270:273	disease risk	262:273	disease risk	262:273	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	8	46	theme	Multivariate	1147:1158	arg1	analysis					1160:1167	Multivariate analysis	1147:1167	Multivariate analysis	1147:1167	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	3	47	theme	intracellular	458:470	arg1	proteins					472:479	intracellular proteins	458:479	intracellular proteins	458:479	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	7	48	from	OS	1075:1076	arg1	patients					1081:1088	patients	1081:1088	patients with EGFR wild-type tumors at variable stages (P=0.038)	1081:1144	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	5	49	theme	lung	761:764	arg1	adenocarcinoma					766:779	lung adenocarcinoma	761:779	lung adenocarcinoma	761:779	We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma.
30123425	7	50	theme	wild-type	1100:1108	arg1	tumors					1110:1115	EGFR wild-type tumors	1095:1115	EGFR wild-type tumors at variable stages (P=0.038)	1095:1144	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	1	51	dep	cancer	211:216	arg1	challenge					220:228	a challenge	218:228	lung cancer a challenge	206:228	Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge.
30123425	7	52	theme	EGFR	1095:1098	arg1	tumors					1110:1115	EGFR wild-type tumors	1095:1115	EGFR wild-type tumors at variable stages (P=0.038)	1095:1144	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	6	53	theme	I	876:876	arg1	patients					878:885	stage I patients	870:885	stage I patients (P=0.032)	870:895	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	53	theme	I	876:876	arg1	P=0.032					888:894	P=0.032	888:894	P=0.032	888:894	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	2	54	theme	predictive	248:257	arg1	biomarkers					237:246	Novel biomarkers	231:246	Novel biomarkers predictive of disease risk and treatment response	231:296	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	6	55	theme	OGT	801:803	arg1	expression					805:814	high OGT expression	796:814	high OGT expression	796:814	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	1	56	theme	Tumor	130:134	arg1	heterogeneity					141:153	Tumor cell heterogeneity	130:153	Tumor cell heterogeneity	130:153	Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge.
30123425	0	57	theme	poor	66:69	arg1	survival					71:78	poor survival	66:78	poor survival in patients with early stage lung adenocarcinoma	66:127	High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma.
30123425	2	58	theme	Novel	231:235	arg1	biomarkers					237:246	Novel biomarkers	231:246	Novel biomarkers predictive of disease risk and treatment response	231:296	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	6	59	from	survival	848:855	arg1	those					901:905	those	901:905	those	901:905	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	59	from	survival	848:855	arg1	patients					878:885	stage I patients	870:885	stage I patients (P=0.032)	870:895	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	59	from	survival	848:855	arg1	P=0.032					888:894	P=0.032	888:894	P=0.032	888:894	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	59	from	survival	848:855	arg1	stages					919:924	variable stages	910:924	variable stages of disease (P=0.029)	910:945	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	60	theme	high	796:799	arg1	expression					805:814	high OGT expression	796:814	high OGT expression	796:814	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	1	61	theme	cell	136:139	arg1	heterogeneity					141:153	Tumor cell heterogeneity	130:153	Tumor cell heterogeneity	130:153	Tumor cell heterogeneity can make selection of appropriate interventions to lung cancer a challenge.
30123425	7	62	theme	variable	1120:1127	arg1	stages					1129:1134	variable stages	1120:1134	variable stages (P=0.038)	1120:1144	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	7	62	theme	variable	1120:1127	arg1	P=0.038					1137:1143	P=0.038	1137:1143	P=0.038	1137:1143	High OGT expression is also associated with poorer OS in patients with EGFR wild-type tumors at variable stages (P=0.038).
30123425	5	63	theme	O-GlcNAc	724:731	arg1	utility					699:705	the utility	695:705	the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma	695:779	We used immunohistochemistry to explore the utility of OGT, OGA, and O-GlcNAc as potential biomarkers for lung adenocarcinoma.
30123425	8	64	dep	HR	1292:1293	arg1	1.183-3.391					1310:1320	1.183-3.391	1310:1320	1.183-3.391	1310:1320	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	8	64	dep	HR	1292:1293	arg1	P=0.010					1323:1329	P=0.010	1323:1329	P=0.010	1323:1329	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	2	65	theme	response	289:296	arg1	predictive					248:257	predictive	248:257	predictive	248:257	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	8	66	theme	prognostic	1217:1226	arg1	factor					1228:1233	an independent prognostic factor	1202:1233	an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients	1202:1350	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	8	66	theme	prognostic	1217:1226	arg1	expression					1188:1197	OGT expression	1184:1197	OGT expression	1184:1197	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	3	67	gly	O-GlcNAcylation	355:369	arg1	pathogenesis					538:549	cancer pathogenesis	531:549	cancer pathogenesis	531:549	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	2	68	theme	treatment	279:287	arg1	response					289:296	treatment response	279:296	treatment response	279:296	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	3	69	theme	cancer	531:536	arg1	pathogenesis					538:549	cancer pathogenesis	531:549	cancer pathogenesis	531:549	O-GlcNAcylation, the attachment of β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of intracellular proteins, modulates protein functions and is implicated in cancer pathogenesis.
30123425	6	70	theme	I	1002:1002	arg1	P=0.035					1014:1020	P=0.035	1014:1020	P=0.035	1014:1020	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	70	theme	I	1002:1002	arg1	patients					1004:1011	stage I patients	996:1011	stage I patients (P=0.035)	996:1021	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	71	from	stages	919:924	arg1	survival					848:855	poor overall survival	835:855	poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029)	835:945	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	71	from	stages	919:924	arg1	OS					858:859	OS	858:859	OS	858:859	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	8	72	from	RFS	1239:1241	arg1	patients					1343:1350	stage I patients	1335:1350	stage I patients	1335:1350	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	9	73	theme	promising	1384:1392	arg1	biomarker					1394:1402	a promising biomarker	1382:1402	a promising biomarker for further classifying early stage lung adenocarcinomas	1382:1459	Our findings indicate OGT is a promising biomarker for further classifying early stage lung adenocarcinomas.
30123425	9	73	theme	promising	1384:1392	arg1	OGT					1375:1377	OGT	1375:1377	OGT	1375:1377	Our findings indicate OGT is a promising biomarker for further classifying early stage lung adenocarcinomas.
30123425	8	74	dep	HR	1244:1245	arg1	P=0.004					1275:1281	P=0.004	1275:1281	P=0.004	1275:1281	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	8	74	dep	HR	1244:1245	arg1	%					1256:1256	95% CI: 1.411-6.150	1254:1272	95% CI: 1.411-6.150	1254:1272	Multivariate analysis indicated that OGT expression is an independent prognostic factor for RFS (HR 2.946, 95% CI: 1.411-6.150, P=0.004) and OS (HR 2.002, 95% CI: 1.183-3.391, P=0.010) in stage I patients.
30123425	6	75	theme	stage	996:1000	arg1	P=0.035					1014:1020	P=0.035	1014:1020	P=0.035	1014:1020	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	75	theme	stage	996:1000	arg1	patients					1004:1011	stage I patients	996:1011	stage I patients (P=0.035)	996:1021	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	6	76	theme	disease	929:935	arg1	stages					919:924	variable stages	910:924	variable stages of disease (P=0.029)	910:945	We found that high OGT expression is associated with poor overall survival (OS) in both stage I patients (P=0.032) and those at variable stages of disease (P=0.029), and with poor recurrence-free survival (RFS) in stage I patients (P=0.035).
30123425	2	77	theme	risk	270:273	arg1	predictive					248:257	predictive	248:257	predictive	248:257	Novel biomarkers predictive of disease risk and treatment response are needed to improve personalized treatment strategies.
30123425	9	78	theme	early	1428:1432	arg1	adenocarcinomas					1445:1459	early stage lung adenocarcinomas	1428:1459	early stage lung adenocarcinomas	1428:1459	Our findings indicate OGT is a promising biomarker for further classifying early stage lung adenocarcinomas.
30620550	7	0	theme	powerful	1138:1145	arg1	tool					1147:1150	a powerful tool	1136:1150	a powerful tool to profile O-GlcNAcylation dynamics in cells	1136:1195	Thus, this probe provides a powerful tool to profile O-GlcNAcylation dynamics in cells.
30620550	1	1	theme	proteins	185:192	arg1	N-acetylglucosamine					102:120	O-linked N-acetylglucosamine	93:120	O-linked N-acetylglucosamine ( O-GlcNAc)	93:132	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	1	1	theme	proteins	185:192	arg1	modification					169:180	a ubiquitous post-translational modification	137:180	a ubiquitous post-translational modification of proteins	137:192	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	2	2	from	mechanisms	335:344	arg1	cells					389:393	cells	389:393	cells	389:393	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	6	3	theme	O-GlcNAcylation	1056:1070	arg1	investigation					1039:1051	mechanistic investigation	1027:1051	mechanistic investigation of O-GlcNAcylation	1027:1070	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	5	4	theme	O-GlcNAcylation	753:767	arg1	sites					769:773	O-GlcNAcylation sites	753:773	O-GlcNAcylation sites in 293T cells	753:787	We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels.
30620550	2	5	from	roles	361:365	arg1	cells					389:393	cells	389:393	cells	389:393	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	4	6	theme	cellular	664:671	arg1	mixtures					673:680	complex cellular mixtures	656:680	complex cellular mixtures	656:680	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	4	7	theme	isotopic	594:601	arg1	labeling					603:610	isotopic labeling	594:610	isotopic labeling	594:610	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	6	8	theme	sorafenib-sensitive	933:951	arg1	cells					990:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	2	9	theme	cellular	326:333	arg1	mechanisms					335:344	cellular mechanisms	326:344	cellular mechanisms	326:344	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	1	10	link	O-linked	93:100	arg1	O-GlcNAc					124:131	O-GlcNAc	124:131	O-GlcNAc	124:131	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	1	10	link	O-linked	93:100	arg1	modification					169:180	a ubiquitous post-translational modification	137:180	a ubiquitous post-translational modification of proteins	137:192	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	1	10	link	O-linked	93:100	arg1	N-acetylglucosamine					102:120	O-linked N-acetylglucosamine	93:120	O-linked N-acetylglucosamine ( O-GlcNAc)	93:132	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	4	11	from	mixtures	673:680	arg1	step					646:649	one step	642:649	one step from complex cellular mixtures	642:680	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	6	12	theme	mechanistic	1027:1037	arg1	investigation					1039:1051	mechanistic investigation	1027:1051	mechanistic investigation of O-GlcNAcylation	1027:1070	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	6	13	theme	O-GlcNAcylation	909:923	arg1	stoichiometry					892:904	the stoichiometry	888:904	the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance	888:1107	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	4	14	theme	selective	572:580	arg1	tagging					582:588	selective tagging	572:588	selective tagging	572:588	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	5	15	theme	probe	721:725	arg1	application					702:712	the application	698:712	the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels	698:830	We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels.
30620550	1	16	theme	O-linked	93:100	arg1	O-GlcNAc					124:131	O-GlcNAc	124:131	O-GlcNAc	124:131	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	1	16	theme	O-linked	93:100	arg1	modification					169:180	a ubiquitous post-translational modification	137:180	a ubiquitous post-translational modification of proteins	137:192	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	1	16	theme	O-linked	93:100	arg1	N-acetylglucosamine					102:120	O-linked N-acetylglucosamine	93:120	O-linked N-acetylglucosamine ( O-GlcNAc)	93:132	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	3	17	theme	quantitative	504:515	arg1	proteomics					541:550	quantitative mass spectrometry-based proteomics	504:550	quantitative mass spectrometry-based proteomics	504:550	Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics.
30620550	0	18	theme	Isotope-Coded	3:15	arg1	Probe					32:36	An Isotope-Coded Photocleavable Probe	0:36	An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation	0:90	An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation.
30620550	3	19	theme	O-GlcNAcylation	473:487	arg1	dynamics					489:496	protein O-GlcNAcylation dynamics	465:496	protein O-GlcNAcylation dynamics	465:496	Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics.
30620550	3	20	theme	photocleavable	430:443	arg1	probe					445:449	an isotope-coded photocleavable probe	413:449	an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics	413:550	Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics.
30620550	6	21	theme	cancer	1086:1091	arg1	chemoresistance					1093:1107	cancer chemoresistance	1086:1107	cancer chemoresistance	1086:1107	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	2	22	theme	functional	350:359	arg1	roles					361:365	functional roles	350:365	functional roles of O-GlcNAcylation in cells	350:393	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	1	23	theme	cell	215:218	arg1	function					220:227	cell function	215:227	cell function	215:227	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	0	24	theme	Photocleavable	17:30	arg1	Probe					32:36	An Isotope-Coded Photocleavable Probe	0:36	An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation	0:90	An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation.
30620550	4	25	theme	complex	656:662	arg1	mixtures					673:680	complex cellular mixtures	656:680	complex cellular mixtures	656:680	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	0	26	theme	Quantitative	42:53	arg1	Profiling					55:63	Quantitative Profiling	42:63	Quantitative Profiling of Protein O-GlcNAcylation	42:90	An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation.
30620550	5	27	theme	O-GlcNAc	816:823	arg1	levels					825:830	O-GlcNAc levels	816:830	O-GlcNAc levels	816:830	We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels.
30620550	7	28	from	dynamics	1179:1186	arg1	cells					1191:1195	cells	1191:1195	cells	1191:1195	Thus, this probe provides a powerful tool to profile O-GlcNAcylation dynamics in cells.
30620550	3	29	theme	mass	517:520	arg1	proteomics					541:550	quantitative mass spectrometry-based proteomics	504:550	quantitative mass spectrometry-based proteomics	504:550	Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics.
30620550	3	30	theme	protein	465:471	arg1	dynamics					489:496	protein O-GlcNAcylation dynamics	465:496	protein O-GlcNAcylation dynamics	465:496	Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics.
30620550	4	31	theme	O-GlcNAcylated	615:628	arg1	proteins					630:637	O-GlcNAcylated proteins	615:637	O-GlcNAcylated proteins	615:637	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	5	32	theme	levels	825:830	arg1	induction					803:811	chemical induction	794:811	chemical induction of O-GlcNAc levels	794:830	We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels.
30620550	2	33	theme	O-GlcNAcylation	258:272	arg1	dynamics					246:253	the dynamics	242:253	the dynamics of O-GlcNAcylation	242:272	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	3	34	theme	spectrometry-based	522:539	arg1	proteomics					541:550	quantitative mass spectrometry-based proteomics	504:550	quantitative mass spectrometry-based proteomics	504:550	Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics.
30620550	5	35	from	sites	769:773	arg1	cells					783:787	293T cells	778:787	293T cells	778:787	We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels.
30620550	5	36	theme	293T	778:781	arg1	cells					783:787	293T cells	778:787	293T cells	778:787	We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels.
30620550	7	37	theme	profile	1155:1161	arg1	dynamics					1179:1186	profile O-GlcNAcylation dynamics	1155:1186	profile O-GlcNAcylation dynamics in cells	1155:1195	Thus, this probe provides a powerful tool to profile O-GlcNAcylation dynamics in cells.
30620550	4	38	theme	proteins	630:637	arg1	tagging					582:588	selective tagging	572:588	selective tagging	572:588	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	4	38	theme	proteins	630:637	arg1	labeling					603:610	isotopic labeling	594:610	isotopic labeling	594:610	This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures.
30620550	6	39	theme	cancer	983:988	arg1	cells					990:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	7	40	theme	O-GlcNAcylation	1163:1177	arg1	dynamics					1179:1186	profile O-GlcNAcylation dynamics	1155:1186	profile O-GlcNAcylation dynamics in cells	1155:1195	Thus, this probe provides a powerful tool to profile O-GlcNAcylation dynamics in cells.
30620550	1	41	theme	ubiquitous	139:148	arg1	N-acetylglucosamine					102:120	O-linked N-acetylglucosamine	93:120	O-linked N-acetylglucosamine ( O-GlcNAc)	93:132	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	1	41	theme	ubiquitous	139:148	arg1	modification					169:180	a ubiquitous post-translational modification	137:180	a ubiquitous post-translational modification of proteins	137:192	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	5	42	theme	chemical	794:801	arg1	induction					803:811	chemical induction	794:811	chemical induction of O-GlcNAc levels	794:830	We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels.
30620550	6	43	theme	liver	977:981	arg1	cells					990:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	1	44	theme	post-translational	150:167	arg1	N-acetylglucosamine					102:120	O-linked N-acetylglucosamine	93:120	O-linked N-acetylglucosamine ( O-GlcNAc)	93:132	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	1	44	theme	post-translational	150:167	arg1	modification					169:180	a ubiquitous post-translational modification	137:180	a ubiquitous post-translational modification of proteins	137:192	O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function.
30620550	2	45	theme	O-GlcNAcylation	370:384	arg1	mechanisms					335:344	cellular mechanisms	326:344	cellular mechanisms	326:344	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	2	45	theme	O-GlcNAcylation	370:384	arg1	roles					361:365	functional roles	350:365	functional roles of O-GlcNAcylation in cells	350:393	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	0	46	theme	O-GlcNAcylation	76:90	arg1	Profiling					55:63	Quantitative Profiling	42:63	Quantitative Profiling of Protein O-GlcNAcylation	42:90	An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation.
30620550	6	47	theme	sorafenib-resistant	957:975	arg1	cells					990:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	sorafenib-sensitive and sorafenib-resistant liver cancer cells	933:994	We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance.
30620550	2	48	theme	proteome-wide	279:291	arg1	level					293:297	a proteome-wide level	277:297	a proteome-wide level	277:297	Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells.
30620550	0	49	theme	Protein	68:74	arg1	O-GlcNAcylation					76:90	Protein O-GlcNAcylation	68:90	Protein O-GlcNAcylation	68:90	An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation.
30620550	3	50	theme	isotope-coded	416:428	arg1	probe					445:449	an isotope-coded photocleavable probe	413:449	an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics	413:550	Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics.
31327066	7	0	mod	modified	1015:1022	arg1	electrode					1001:1009	A glassy carbon electrode	985:1009	A glassy carbon electrode	985:1009	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	7	0	mod	modified	1015:1022	arg3	N-rGO/CD-Cu-CMC					1029:1043	N-rGO/CD-Cu-CMC	1029:1043	N-rGO/CD-Cu-CMC	1029:1043	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	2	1	theme	pulse	512:516	arg1	voltammetry					518:528	differential pulse voltammetry	499:528	differential pulse voltammetry that was used for enantiorecognition	499:565	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	12	2	theme	abstract	1586:1593	arg1	representation					1605:1618	Graphical abstract Schematic representation	1576:1618	Graphical abstract Schematic representation of an electrochemical chirality sensor	1576:1657	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	10	3	theme	0.0035 μM	1374:1382	arg1	detection					1348:1356	detection	1348:1356	detection of 0.063 μM and 0.0035 μM	1348:1382	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	7	4	theme	glassy	987:992	arg1	electrode					1001:1009	A glassy carbon electrode	985:1009	A glassy carbon electrode	985:1009	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	15	5	with	combination	1881:1891	arg1	Cu-β-CD					1931:1937	Cu-β-CD	1931:1937	Cu-β-CD	1931:1937	The combination of carboxymethyl cellulose (CMC) with Cu-β-CD leads to a novel self-assembly framework.
31327066	13	6	theme	material	1768:1775	arg1	preparation					1719:1729	the preparation	1715:1729	the preparation of a chiral selector and a substrate material	1715:1775	It involves the preparation of a chiral selector and a substrate material.
31327066	10	7	theme	linear	1426:1431	arg1	range					1442:1446	a linear response range	1424:1446	a linear response range of 0.01 mM to 5 mM	1424:1465	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	13	8	theme	selector	1743:1750	arg1	preparation					1719:1729	the preparation	1715:1729	the preparation of a chiral selector and a substrate material	1715:1775	It involves the preparation of a chiral selector and a substrate material.
31327066	1	9	theme	L-	212:213	arg1	recognition					197:207	the enantioselective recognition	176:207	the enantioselective recognition of L- and D-tryptophan (Trp)	176:236	A chiral sensor is described for the enantioselective recognition of L- and D-tryptophan (Trp).
31327066	1	10	theme	D-tryptophan	219:230	arg1	recognition					197:207	the enantioselective recognition	176:207	the enantioselective recognition of L- and D-tryptophan (Trp)	176:236	A chiral sensor is described for the enantioselective recognition of L- and D-tryptophan (Trp).
31327066	11	11	used	used	1483:1486	arg2	sensor					1472:1477	The sensor	1468:1477	The sensor	1468:1477	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	14	12	dep	oxide	1840:1844	arg1	GO					1847:1848	GO	1847:1848	GO	1847:1848	N-Doped graphene oxide (N-rGO) was prepared by using graphene oxide (GO) and pyrrole as precursor.
31327066	5	13	theme	XPS	784:786	arg1	techniques					788:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques showed that 3D N-rGO and the CD-Cu-CMC composite were successfully synthesized.
31327066	2	14	theme	reduced	433:439	arg1	oxide					450:454	N-doped reduced graphene oxide	425:454	N-doped reduced graphene oxide (N-rGO)	425:462	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	14	theme	reduced	433:439	arg1	N-rGO					457:461	N-rGO	457:461	N-rGO	457:461	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	7	15	theme	0.78 V	1164:1169	arg1	potential					1144:1152	a working potential	1134:1152	a working potential of around 0.78 V (vs. SCE)	1134:1179	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	11	16	theme	real	1526:1529	arg1	urine					1537:1541	spiked real human urine	1519:1541	spiked real human urine	1519:1541	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	0	17	theme	3D	66:67	arg1	oxide					101:105	3D nitrogen-doped reduced graphene oxide	66:105	3D nitrogen-doped reduced graphene oxide	66:105	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	5	18	theme	SEM	771:773	arg1	techniques					788:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques showed that 3D N-rGO and the CD-Cu-CMC composite were successfully synthesized.
31327066	6	19	theme	3D	883:884	arg1	N-rGO					886:890	The 3D N-rGO	879:890	The 3D N-rGO	879:890	The 3D N-rGO enabled the immobilization of the chiral selector (CD-Cu-CMC) and improves the active areas.
31327066	11	20	theme	protein	1559:1565	arg1	samples					1567:1573	human serum protein samples	1547:1573	human serum protein samples	1547:1573	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	0	21	theme	reduced	84:90	arg1	oxide					101:105	3D nitrogen-doped reduced graphene oxide	66:105	3D nitrogen-doped reduced graphene oxide	66:105	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	5	22	theme	XRD	776:778	arg1	techniques					788:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques showed that 3D N-rGO and the CD-Cu-CMC composite were successfully synthesized.
31327066	11	23	from	Trp	1498:1500	arg1	urine					1537:1541	spiked real human urine	1519:1541	spiked real human urine	1519:1541	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	11	23	from	Trp	1498:1500	arg1	samples					1567:1573	human serum protein samples	1547:1573	human serum protein samples	1547:1573	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	11	24	theme	human	1547:1551	arg1	samples					1567:1573	human serum protein samples	1547:1573	human serum protein samples	1547:1573	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	7	25	theme	electrochemical	1072:1086	arg1	signal					1088:1093	a stronger electrochemical signal	1061:1093	a stronger electrochemical signal for L-Trp	1061:1103	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	5	26	theme	CD-Cu-CMC	828:836	arg1	composite					838:846	the CD-Cu-CMC composite	824:846	the CD-Cu-CMC composite	824:846	The FT-IR, SEM, XRD and XPS techniques showed that 3D N-rGO and the CD-Cu-CMC composite were successfully synthesized.
31327066	2	27	theme	oxide	450:454	arg1	β-cyclodextrin					306:319	β-cyclodextrin	306:319	β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials	306:485	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	27	theme	oxide	450:454	arg1	selector					408:415	a chiral selector	399:415	a chiral selector	399:415	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	27	theme	oxide	450:454	arg1	b					419:419	b	419:419	b	419:419	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	0	28	theme	self-assembled	111:124	arg1	polysaccharides					126:140	self-assembled polysaccharides	111:140	self-assembled polysaccharides	111:140	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	2	29	theme	chiral	401:406	arg1	β-cyclodextrin					306:319	β-cyclodextrin	306:319	β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials	306:485	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	29	theme	chiral	401:406	arg1	selector					408:415	a chiral selector	399:415	a chiral selector	399:415	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	29	theme	chiral	401:406	arg1	b					419:419	b	419:419	b	419:419	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	0	30	theme	Electrochemical	0:14	arg1	sensing					23:29	Electrochemical chiral sensing	0:29	Electrochemical chiral sensing of tryptophan	0:43	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	5	31	theme	3D	811:812	arg1	N-rGO					814:818	3D N-rGO	811:818	3D N-rGO	811:818	The FT-IR, SEM, XRD and XPS techniques showed that 3D N-rGO and the CD-Cu-CMC composite were successfully synthesized.
31327066	6	32	theme	selector	933:940	arg1	immobilization					904:917	the immobilization	900:917	the immobilization of the chiral selector (CD-Cu-CMC)	900:952	The 3D N-rGO enabled the immobilization of the chiral selector (CD-Cu-CMC) and improves the active areas.
31327066	8	33	theme	higher	1230:1235	arg1	affinity					1237:1244	a higher affinity	1228:1244	a higher affinity for D-Trp	1228:1254	UV-vis spectroscopy proved that CD-Cu-CMC has a higher affinity for D-Trp.
31327066	14	34	theme	N-Doped	1778:1784	arg1	oxide					1795:1799	N-Doped graphene oxide	1778:1799	N-Doped graphene oxide (N-rGO)	1778:1807	N-Doped graphene oxide (N-rGO) was prepared by using graphene oxide (GO) and pyrrole as precursor.
31327066	14	34	theme	N-Doped	1778:1784	arg1	N-rGO					1802:1806	N-rGO	1802:1806	N-rGO	1802:1806	N-Doped graphene oxide (N-rGO) was prepared by using graphene oxide (GO) and pyrrole as precursor.
31327066	0	35	theme	tryptophan	34:43	arg1	sensing					23:29	Electrochemical chiral sensing	0:29	Electrochemical chiral sensing of tryptophan	0:43	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	15	36	theme	carboxymethyl	1896:1908	arg1	CMC					1921:1923	CMC	1921:1923	CMC	1921:1923	The combination of carboxymethyl cellulose (CMC) with Cu-β-CD leads to a novel self-assembly framework.
31327066	15	36	theme	carboxymethyl	1896:1908	arg1	cellulose					1910:1918	carboxymethyl cellulose	1896:1918	carboxymethyl cellulose (CMC)	1896:1924	The combination of carboxymethyl cellulose (CMC) with Cu-β-CD leads to a novel self-assembly framework.
31327066	7	37	theme	around	1157:1162	arg1	0.78 V					1164:1169	around 0.78 V	1157:1169	around 0.78 V (vs. SCE)	1157:1179	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	7	37	theme	around	1157:1162	arg1	SCE					1176:1178	SCE	1176:1178	SCE	1176:1178	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	12	38	theme	chirality	1642:1650	arg1	sensor					1652:1657	an electrochemical chirality sensor	1623:1657	an electrochemical chirality sensor	1623:1657	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	12	39	theme	electrochemical	1626:1640	arg1	sensor					1652:1657	an electrochemical chirality sensor	1623:1657	an electrochemical chirality sensor	1623:1657	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	11	40	theme	spiked	1519:1524	arg1	urine					1537:1541	spiked real human urine	1519:1541	spiked real human urine	1519:1541	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	4	41	theme	carboxy	710:716	arg1	groups					718:723	the carboxy groups	706:723	the carboxy groups of CMC and Cu(II) ions in Cu-β-CD	706:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	41	theme	carboxy	710:716	arg1	ions					743:746	Cu(II) ions	736:746	Cu(II) ions in Cu-β-CD	736:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	41	theme	carboxy	710:716	arg1	CMC					728:730	CMC	728:730	CMC	728:730	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	11	42	dep	Trp	1498:1500	arg1	D-					1503:1504	D-	1503:1504	D-	1503:1504	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	11	42	dep	Trp	1498:1500	arg1	L-Trp					1509:1513	L-Trp	1509:1513	L-Trp	1509:1513	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	12	43	theme	Graphical	1576:1584	arg1	representation					1605:1618	Graphical abstract Schematic representation	1576:1618	Graphical abstract Schematic representation of an electrochemical chirality sensor	1576:1657	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	12	44	theme	Schematic	1595:1603	arg1	representation					1605:1618	Graphical abstract Schematic representation	1576:1618	Graphical abstract Schematic representation of an electrochemical chirality sensor	1576:1657	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	3	45	theme	graphene	611:618	arg1	materials					654:662	the starting materials	641:662	the starting materials	641:662	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	3	45	theme	graphene	611:618	arg1	pyrrole					630:636	pyrrole	630:636	pyrrole	630:636	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	3	45	theme	graphene	611:618	arg1	oxide					620:624	reduced graphene oxide	603:624	reduced graphene oxide	603:624	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	2	46	theme	differential	499:510	arg1	voltammetry					518:528	differential pulse voltammetry	499:528	differential pulse voltammetry that was used for enantiorecognition	499:565	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	13	47	theme	substrate	1758:1766	arg1	material					1768:1775	a substrate material	1756:1775	a substrate material	1756:1775	It involves the preparation of a chiral selector and a substrate material.
31327066	1	48	theme	enantioselective	180:195	arg1	recognition					197:207	the enantioselective recognition	176:207	the enantioselective recognition of L- and D-tryptophan (Trp)	176:236	A chiral sensor is described for the enantioselective recognition of L- and D-tryptophan (Trp).
31327066	10	49	theme	response	1433:1440	arg1	range					1442:1446	a linear response range	1424:1446	a linear response range of 0.01 mM to 5 mM	1424:1465	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	13	50	theme	chiral	1736:1741	arg1	selector					1743:1750	a chiral selector	1734:1750	a chiral selector	1734:1750	It involves the preparation of a chiral selector and a substrate material.
31327066	14	51	theme	graphene	1831:1838	arg1	oxide					1840:1844	graphene oxide	1831:1844	graphene oxide (GO)	1831:1849	N-Doped graphene oxide (N-rGO) was prepared by using graphene oxide (GO) and pyrrole as precursor.
31327066	2	52	theme	voltammetry	518:528	arg1	use					266:268	the use	262:268	the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition	262:565	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	52	theme	voltammetry	518:528	arg1	a					274:274	a	274:274	a	274:274	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	53	theme	Cu	277:278	arg1	ions					284:287	Cu(II) ions	277:287	Cu(II) ions	277:287	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	54	theme	substrate	467:475	arg1	materials					477:485	substrate materials	467:485	substrate materials	467:485	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	54	theme	substrate	467:475	arg1	β-cyclodextrin					306:319	β-cyclodextrin	306:319	β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials	306:485	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	15	55	theme	novel	1950:1954	arg1	framework					1970:1978	a novel self-assembly framework	1948:1978	a novel self-assembly framework	1948:1978	The combination of carboxymethyl cellulose (CMC) with Cu-β-CD leads to a novel self-assembly framework.
31327066	3	56	theme	starting	645:652	arg1	materials					654:662	the starting materials	641:662	the starting materials	641:662	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	3	56	theme	starting	645:652	arg1	pyrrole					630:636	pyrrole	630:636	pyrrole	630:636	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	3	56	theme	starting	645:652	arg1	oxide					620:624	reduced graphene oxide	603:624	reduced graphene oxide	603:624	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	5	57	theme	FT-IR	764:768	arg1	techniques					788:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques	760:797	The FT-IR, SEM, XRD and XPS techniques showed that 3D N-rGO and the CD-Cu-CMC composite were successfully synthesized.
31327066	15	58	theme	cellulose	1910:1918	arg1	combination					1881:1891	The combination	1877:1891	The combination of carboxymethyl cellulose (CMC) with Cu-β-CD	1877:1937	The combination of carboxymethyl cellulose (CMC) with Cu-β-CD leads to a novel self-assembly framework.
31327066	10	59	contain	had	1333:1335	arg2	limit					1339:1343	a limit	1337:1343	a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp	1337:1402	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	10	59	contain	had	1333:1335	arg1	electrode					1323:1331	The modified electrode	1310:1331	The modified electrode	1310:1331	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	4	60	from	CMC	728:730	arg1	Cu-β-CD					751:757	Cu-β-CD	751:757	Cu-β-CD	751:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	1	61	theme	chiral	145:150	arg1	sensor					152:157	A chiral sensor	143:157	A chiral sensor	143:157	A chiral sensor is described for the enantioselective recognition of L- and D-tryptophan (Trp).
31327066	0	62	theme	nitrogen-doped	69:82	arg1	oxide					101:105	3D nitrogen-doped reduced graphene oxide	66:105	3D nitrogen-doped reduced graphene oxide	66:105	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	4	63	from	groups	718:723	arg1	Cu-β-CD					751:757	Cu-β-CD	751:757	Cu-β-CD	751:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	15	64	theme	self-assembly	1956:1968	arg1	framework					1970:1978	a novel self-assembly framework	1948:1978	a novel self-assembly framework	1948:1978	The combination of carboxymethyl cellulose (CMC) with Cu-β-CD leads to a novel self-assembly framework.
31327066	2	65	theme	N-doped	425:431	arg1	oxide					450:454	N-doped reduced graphene oxide	425:454	N-doped reduced graphene oxide (N-rGO)	425:462	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	65	theme	N-doped	425:431	arg1	N-rGO					457:461	N-rGO	457:461	N-rGO	457:461	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	11	66	theme	human	1531:1535	arg1	urine					1537:1541	spiked real human urine	1519:1541	spiked real human urine	1519:1541	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	0	67	theme	graphene	92:99	arg1	oxide					101:105	3D nitrogen-doped reduced graphene oxide	66:105	3D nitrogen-doped reduced graphene oxide	66:105	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	8	68	contain	has	1224:1226	arg2	affinity					1237:1244	a higher affinity	1228:1244	a higher affinity for D-Trp	1228:1254	UV-vis spectroscopy proved that CD-Cu-CMC has a higher affinity for D-Trp.
31327066	8	68	contain	has	1224:1226	arg1	CD-Cu-CMC					1214:1222	CD-Cu-CMC	1214:1222	CD-Cu-CMC	1214:1222	UV-vis spectroscopy proved that CD-Cu-CMC has a higher affinity for D-Trp.
31327066	7	69	theme	stronger	1063:1070	arg1	signal					1088:1093	a stronger electrochemical signal	1061:1093	a stronger electrochemical signal for L-Trp	1061:1103	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	4	70	from	Cu-β-CD	751:757	arg1	groups					718:723	the carboxy groups	706:723	the carboxy groups of CMC and Cu(II) ions in Cu-β-CD	706:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	70	from	Cu-β-CD	751:757	arg1	ions					743:746	Cu(II) ions	736:746	Cu(II) ions in Cu-β-CD	736:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	70	from	Cu-β-CD	751:757	arg1	CMC					728:730	CMC	728:730	CMC	728:730	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	8	71	theme	UV-vis	1182:1187	arg1	spectroscopy					1189:1200	UV-vis spectroscopy	1182:1200	UV-vis spectroscopy	1182:1200	UV-vis spectroscopy proved that CD-Cu-CMC has a higher affinity for D-Trp.
31327066	4	72	theme	Electrostatic	665:677	arg1	interaction					679:689	Electrostatic interaction	665:689	Electrostatic interaction	665:689	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	11	73	theme	serum	1553:1557	arg1	samples					1567:1573	human serum protein samples	1547:1573	human serum protein samples	1547:1573	The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples.
31327066	4	74	from	ions	743:746	arg1	Cu-β-CD					751:757	Cu-β-CD	751:757	Cu-β-CD	751:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	12	75	theme	CD-Cu-CMC	1692:1700	arg1	merits					1672:1677	the merits	1668:1677	the merits of N-rGO and CD-Cu-CMC	1668:1700	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	2	76	theme	graphene	441:448	arg1	oxide					450:454	N-doped reduced graphene oxide	425:454	N-doped reduced graphene oxide (N-rGO)	425:462	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	76	theme	graphene	441:448	arg1	N-rGO					457:461	N-rGO	457:461	N-rGO	457:461	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	10	77	theme	modified	1314:1321	arg1	electrode					1323:1331	The modified electrode	1310:1331	The modified electrode	1310:1331	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	0	78	theme	chiral	16:21	arg1	sensing					23:29	Electrochemical chiral sensing	0:29	Electrochemical chiral sensing of tryptophan	0:43	Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.
31327066	2	79	used	used	539:542	arg2	voltammetry					518:528	differential pulse voltammetry	499:528	differential pulse voltammetry that was used for enantiorecognition	499:565	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	10	80	theme	5 mM	1462:1465	arg1	range					1442:1446	a linear response range	1424:1446	a linear response range of 0.01 mM to 5 mM	1424:1465	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	14	81	theme	graphene	1786:1793	arg1	oxide					1795:1799	N-Doped graphene oxide	1778:1799	N-Doped graphene oxide (N-rGO)	1778:1807	N-Doped graphene oxide (N-rGO) was prepared by using graphene oxide (GO) and pyrrole as precursor.
31327066	14	81	theme	graphene	1786:1793	arg1	N-rGO					1802:1806	N-rGO	1802:1806	N-rGO	1802:1806	N-Doped graphene oxide (N-rGO) was prepared by using graphene oxide (GO) and pyrrole as precursor.
31327066	6	82	theme	chiral	926:931	arg1	CD-Cu-CMC					943:951	CD-Cu-CMC	943:951	CD-Cu-CMC	943:951	The 3D N-rGO enabled the immobilization of the chiral selector (CD-Cu-CMC) and improves the active areas.
31327066	6	82	theme	chiral	926:931	arg1	selector					933:940	the chiral selector	922:940	the chiral selector (CD-Cu-CMC)	922:952	The 3D N-rGO enabled the immobilization of the chiral selector (CD-Cu-CMC) and improves the active areas.
31327066	2	83	dep	coordinated	289:299	arg1	use					266:268	the use	262:268	the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition	262:565	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	83	dep	coordinated	289:299	arg1	a					274:274	a	274:274	a	274:274	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	12	84	theme	N-rGO	1682:1686	arg1	merits					1672:1677	the merits	1668:1677	the merits of N-rGO and CD-Cu-CMC	1668:1700	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	4	85	theme	CMC	728:730	arg1	groups					718:723	the carboxy groups	706:723	the carboxy groups of CMC and Cu(II) ions in Cu-β-CD	706:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	85	theme	CMC	728:730	arg1	ions					743:746	Cu(II) ions	736:746	Cu(II) ions in Cu-β-CD	736:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	85	theme	CMC	728:730	arg1	CMC					728:730	CMC	728:730	CMC	728:730	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	2	86	theme	carboxymethyl	360:372	arg1	cellulose					374:382	carboxymethyl cellulose	360:382	carboxymethyl cellulose (CD-Cu-CMC)	360:394	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	2	86	theme	carboxymethyl	360:372	arg1	CD-Cu-CMC					385:393	CD-Cu-CMC	385:393	CD-Cu-CMC	385:393	The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition.
31327066	7	87	theme	carbon	994:999	arg1	electrode					1001:1009	A glassy carbon electrode	985:1009	A glassy carbon electrode	985:1009	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	12	88	theme	sensor	1652:1657	arg1	representation					1605:1618	Graphical abstract Schematic representation	1576:1618	Graphical abstract Schematic representation of an electrochemical chirality sensor	1576:1657	Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC.
31327066	4	89	theme	ions	743:746	arg1	groups					718:723	the carboxy groups	706:723	the carboxy groups of CMC and Cu(II) ions in Cu-β-CD	706:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	89	theme	ions	743:746	arg1	ions					743:746	Cu(II) ions	736:746	Cu(II) ions in Cu-β-CD	736:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	4	89	theme	ions	743:746	arg1	CMC					728:730	CMC	728:730	CMC	728:730	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	7	90	theme	working	1136:1142	arg1	potential					1144:1152	a working potential	1134:1152	a working potential of around 0.78 V (vs. SCE)	1134:1179	A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78 V (vs. SCE).
31327066	10	91	theme	0.063 μM	1361:1368	arg1	detection					1348:1356	detection	1348:1356	detection of 0.063 μM and 0.0035 μM	1348:1382	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	4	92	theme	Cu	736:737	arg1	ions					743:746	Cu(II) ions	736:746	Cu(II) ions in Cu-β-CD	736:757	Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD.
31327066	10	93	theme	detection	1348:1356	arg1	limit					1339:1343	a limit	1337:1343	a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp	1337:1402	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	3	94	theme	3D	572:573	arg1	N-rGO					575:579	The 3D N-rGO	568:579	The 3D N-rGO	568:579	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	10	95	dep	5 mM	1462:1465	arg1	to					1459:1460	to	1459:1460	to	1459:1460	The modified electrode had a limit of detection of 0.063 μM and 0.0035 μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01 mM to 5 mM.
31327066	6	96	theme	active	971:976	arg1	areas					978:982	the active areas	967:982	the active areas	967:982	The 3D N-rGO enabled the immobilization of the chiral selector (CD-Cu-CMC) and improves the active areas.
31327066	3	97	theme	reduced	603:609	arg1	materials					654:662	the starting materials	641:662	the starting materials	641:662	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	3	97	theme	reduced	603:609	arg1	pyrrole					630:636	pyrrole	630:636	pyrrole	630:636	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
31327066	3	97	theme	reduced	603:609	arg1	oxide					620:624	reduced graphene oxide	603:624	reduced graphene oxide	603:624	The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials.
30956133	4	0	theme	ligand	496:501	arg1	cargo					389:393	their cargo	383:393	their cargo	383:393	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	0	theme	ligand	496:501	arg1	amphiregulin					504:515	amphiregulin	504:515	amphiregulin (AREG)	504:522	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	0	theme	ligand	496:501	arg1	ST6Gal-I					440:447	ST6Gal-I	440:447	ST6Gal-I	440:447	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	0	theme	ligand	496:501	arg1	α2,6-sialyltransferase					414:435	the β-galactoside α2,6-sialyltransferase 1	396:437	the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans	396:480	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	0	theme	ligand	496:501	arg1	two					376:378	two	376:378	two	376:378	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	0	theme	ligand	496:501	arg1	ligand					496:501	the EGFR ligand	487:501	the EGFR ligand	487:501	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	1	theme	distinct	333:340	arg1	functions					342:350	distinct functions	333:350	distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG)	333:522	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	6	2	theme	recipient	749:757	arg1	cells					759:763	recipient cells	749:763	recipient cells	749:763	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	7	3	theme	functional	1005:1014	arg1	cargo					1016:1020	functional cargo	1005:1020	functional cargo	1005:1020	This study provides a simplified method of exomere isolation and demonstrates that exomeres contain and can transfer functional cargo.
30956133	0	4	from	Transfer	0:7	arg1	Exomeres					32:39	Exomeres	32:39	Exomeres	32:39	Transfer of Functional Cargo in Exomeres.
30956133	5	5	theme	Functional	525:534	arg1	ST6Gal-I					536:543	Functional ST6Gal-I	525:543	Functional ST6Gal-I in exomeres	525:555	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	4	6	theme	α2,6-sialyltransferase	414:435	arg1	cargo					389:393	their cargo	383:393	their cargo	383:393	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	6	theme	α2,6-sialyltransferase	414:435	arg1	amphiregulin					504:515	amphiregulin	504:515	amphiregulin (AREG)	504:522	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	6	theme	α2,6-sialyltransferase	414:435	arg1	ST6Gal-I					440:447	ST6Gal-I	440:447	ST6Gal-I	440:447	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	6	theme	α2,6-sialyltransferase	414:435	arg1	α2,6-sialyltransferase					414:435	the β-galactoside α2,6-sialyltransferase 1	396:437	the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans	396:480	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	6	theme	α2,6-sialyltransferase	414:435	arg1	two					376:378	two	376:378	two	376:378	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	6	theme	α2,6-sialyltransferase	414:435	arg1	ligand					496:501	the EGFR ligand	487:501	the EGFR ligand	487:501	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	2	7	from	separation	213:222	arg1	exosomes					241:248	exosomes	241:248	exosomes	241:248	Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes.
30956133	4	8	theme	β-galactoside	400:412	arg1	ST6Gal-I					440:447	ST6Gal-I	440:447	ST6Gal-I	440:447	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	8	theme	β-galactoside	400:412	arg1	α2,6-sialyltransferase					414:435	the β-galactoside α2,6-sialyltransferase 1	396:437	the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans	396:480	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	7	9	theme	exomere	931:937	arg1	isolation					939:947	exomere isolation	931:947	exomere isolation	931:947	This study provides a simplified method of exomere isolation and demonstrates that exomeres contain and can transfer functional cargo.
30956133	4	10	theme	EGFR	491:494	arg1	ligand					496:501	the EGFR ligand	487:501	the EGFR ligand	487:501	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	5	11	theme	recipient	619:627	arg1	β1-integrin					661:671	β1-integrin	661:671	β1-integrin	661:671	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	5	11	theme	recipient	619:627	arg1	proteins					642:649	recipient cell-surface proteins	619:649	recipient cell-surface proteins including β1-integrin	619:671	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	1	12	theme	discovered	66:75	arg1	type					77:80	a recently discovered type	55:80	a recently discovered type of extracellular nanoparticle with no known biological function	55:144	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	1	12	theme	discovered	66:75	arg1	Exomeres					42:49	Exomeres	42:49	Exomeres	42:49	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	2	13	from	exosomes	241:248	arg1	exomeres					227:234	exomeres	227:234	exomeres from exosomes	227:248	Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes.
30956133	2	13	from	exosomes	241:248	arg1	separation					213:222	separation	213:222	separation of exomeres from exosomes	213:248	Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes.
30956133	5	14	theme	cell-surface	629:640	arg1	β1-integrin					661:671	β1-integrin	661:671	β1-integrin	661:671	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	5	14	theme	cell-surface	629:640	arg1	proteins					642:649	recipient cell-surface proteins	619:649	recipient cell-surface proteins including β1-integrin	619:671	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	5	15	theme	proteins	642:649	arg1	hypersialylation					599:614	hypersialylation	599:614	hypersialylation of recipient cell-surface proteins including β1-integrin	599:671	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	4	16	theme	cargo	389:393	arg1	cargo					389:393	their cargo	383:393	their cargo	383:393	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	16	theme	cargo	389:393	arg1	amphiregulin					504:515	amphiregulin	504:515	amphiregulin (AREG)	504:522	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	16	theme	cargo	389:393	arg1	ST6Gal-I					440:447	ST6Gal-I	440:447	ST6Gal-I	440:447	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	16	theme	cargo	389:393	arg1	α2,6-sialyltransferase					414:435	the β-galactoside α2,6-sialyltransferase 1	396:437	the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans	396:480	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	16	theme	cargo	389:393	arg1	two					376:378	two	376:378	two	376:378	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	16	theme	cargo	389:393	arg1	ligand					496:501	the EGFR ligand	487:501	the EGFR ligand	487:501	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	1	17	with	type	77:80	arg1	function					137:144	no known biological function	117:144	no known biological function	117:144	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	8	18	theme	nanoparticles	1070:1082	arg1	heterogeneity					1053:1065	the heterogeneity	1049:1065	the heterogeneity of nanoparticles	1049:1082	These findings underscore the heterogeneity of nanoparticles and should accelerate advances in determining the composition and biological functions of exomeres.
30956133	8	19	theme	biological	1150:1159	arg1	functions					1161:1169	biological functions	1150:1169	biological functions	1150:1169	These findings underscore the heterogeneity of nanoparticles and should accelerate advances in determining the composition and biological functions of exomeres.
30956133	6	20	theme	intestinal	802:811	arg1	organoids					813:821	normal intestinal organoids	795:821	normal intestinal organoids	795:821	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	1	21	theme	extracellular	85:97	arg1	nanoparticle					99:110	extracellular nanoparticle	85:110	extracellular nanoparticle	85:110	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	6	22	theme	prolonged	706:714	arg1	EGFR					716:719	prolonged EGFR and downstream signaling	706:744	EGFR	716:719	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	0	23	theme	Functional	12:21	arg1	Cargo					23:27	Functional Cargo	12:27	Functional Cargo	12:27	Transfer of Functional Cargo in Exomeres.
30956133	2	24	theme	simple	169:174	arg1	method					202:207	a simple ultracentrifugation-based method	167:207	a simple ultracentrifugation-based method for separation of exomeres from exosomes	167:248	Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes.
30956133	1	25	theme	nanoparticle	99:110	arg1	type					77:80	a recently discovered type	55:80	a recently discovered type of extracellular nanoparticle with no known biological function	55:144	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	1	25	theme	nanoparticle	99:110	arg1	Exomeres					42:49	Exomeres	42:49	Exomeres	42:49	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	5	26	from	ST6Gal-I	536:543	arg1	exomeres					548:555	exomeres	548:555	exomeres	548:555	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	8	27	gly	heterogeneity	1053:1065	arg1	nanoparticles					1070:1082	nanoparticles	1070:1082	nanoparticles	1070:1082	These findings underscore the heterogeneity of nanoparticles and should accelerate advances in determining the composition and biological functions of exomeres.
30956133	0	28	theme	Cargo	23:27	arg1	Transfer					0:7	Transfer	0:7	Transfer of Functional Cargo in Exomeres.	0:40	Transfer of Functional Cargo in Exomeres.
30956133	4	29	theme	exomeres	355:362	arg1	functions					342:350	distinct functions	333:350	distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG)	333:522	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	6	30	from	signaling	736:744	arg1	cells					759:763	recipient cells	749:763	recipient cells	749:763	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	2	31	theme	exomeres	227:234	arg1	separation					213:222	separation	213:222	separation of exomeres from exosomes	213:248	Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes.
30956133	6	32	from	trafficking	780:790	arg1	organoids					813:821	normal intestinal organoids	795:821	normal intestinal organoids	795:821	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	8	33	theme	exomeres	1174:1181	arg1	functions					1161:1169	biological functions	1150:1169	biological functions	1150:1169	These findings underscore the heterogeneity of nanoparticles and should accelerate advances in determining the composition and biological functions of exomeres.
30956133	8	33	theme	exomeres	1174:1181	arg1	composition					1134:1144	composition	1134:1144	composition	1134:1144	These findings underscore the heterogeneity of nanoparticles and should accelerate advances in determining the composition and biological functions of exomeres.
30956133	6	34	theme	organoids	877:885	arg1	growth					853:858	the growth	849:858	the growth of colonic tumor organoids	849:885	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	6	35	theme	AREG-containing	674:688	arg1	exomeres					690:697	AREG-containing exomeres	674:697	AREG-containing exomeres	674:697	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	3	36	theme	amyloid	294:300	arg1	protein					312:318	amyloid precursor protein	294:318	amyloid precursor protein	294:318	Exomeres are enriched in Argonaute 1-3 and amyloid precursor protein.
30956133	6	37	theme	tumor	871:875	arg1	organoids					877:885	colonic tumor organoids	863:885	colonic tumor organoids	863:885	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	6	38	theme	EGFR	775:778	arg1	trafficking					780:790	EGFR trafficking	775:790	EGFR trafficking in normal intestinal organoids	775:821	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	1	39	theme	known	120:124	arg1	function					137:144	no known biological function	117:144	no known biological function	117:144	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	6	40	from	EGFR	716:719	arg1	cells					759:763	recipient cells	749:763	recipient cells	749:763	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	3	41	theme	precursor	302:310	arg1	protein					312:318	amyloid precursor protein	294:318	amyloid precursor protein	294:318	Exomeres are enriched in Argonaute 1-3 and amyloid precursor protein.
30956133	6	42	theme	colonic	863:869	arg1	organoids					877:885	colonic tumor organoids	863:885	colonic tumor organoids	863:885	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	6	43	theme	normal	795:800	arg1	organoids					813:821	normal intestinal organoids	795:821	normal intestinal organoids	795:821	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	1	44	theme	biological	126:135	arg1	function					137:144	no known biological function	117:144	no known biological function	117:144	Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function.
30956133	4	45	gly	sialylates	461:470	arg1	ST6Gal-I					440:447	ST6Gal-I	440:447	ST6Gal-I	440:447	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	45	gly	sialylates	461:470	arg1	N-glycans					472:480	N-glycans	472:480	N-glycans	472:480	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	4	45	gly	sialylates	461:470	arg1	α2,6-sialyltransferase					414:435	the β-galactoside α2,6-sialyltransferase 1	396:437	the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans	396:480	We identify distinct functions of exomeres mediated by two of their cargo, the β-galactoside α2,6-sialyltransferase 1 (ST6Gal-I) that α2,6- sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG).
30956133	6	46	theme	downstream	725:734	arg1	signaling					736:744	prolonged EGFR and downstream signaling	706:744	signaling	736:744	AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids.
30956133	8	47	dep	composition	1134:1144	arg1	the					1130:1132	the	1130:1132	the	1130:1132	These findings underscore the heterogeneity of nanoparticles and should accelerate advances in determining the composition and biological functions of exomeres.
30956133	2	48	theme	ultracentrifugation-based	176:200	arg1	method					202:207	a simple ultracentrifugation-based method	167:207	a simple ultracentrifugation-based method for separation of exomeres from exosomes	167:248	Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes.
30956133	7	49	theme	isolation	939:947	arg1	method					921:926	a simplified method	908:926	a simplified method of exomere isolation	908:947	This study provides a simplified method of exomere isolation and demonstrates that exomeres contain and can transfer functional cargo.
30956133	5	50	gly	hypersialylation	599:614	arg1	β1-integrin					661:671	β1-integrin	661:671	β1-integrin	661:671	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	5	50	gly	hypersialylation	599:614	arg1	proteins					642:649	recipient cell-surface proteins	619:649	recipient cell-surface proteins including β1-integrin	619:671	Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including β1-integrin.
30956133	7	51	contain	contain	980:986	arg2	cargo					1016:1020	functional cargo	1005:1020	functional cargo	1005:1020	This study provides a simplified method of exomere isolation and demonstrates that exomeres contain and can transfer functional cargo.
30956133	7	51	contain	contain	980:986	arg1	exomeres					971:978	exomeres	971:978	exomeres	971:978	This study provides a simplified method of exomere isolation and demonstrates that exomeres contain and can transfer functional cargo.
30956133	7	52	theme	simplified	910:919	arg1	method					921:926	a simplified method	908:926	a simplified method of exomere isolation	908:947	This study provides a simplified method of exomere isolation and demonstrates that exomeres contain and can transfer functional cargo.
31067000	7	0	theme	liquid	1138:1143	arg1	analysis					1173:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis.
31067000	10	1	theme	confidence	1557:1566	arg1	interval					1568:1575	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	11	2	theme	ACPA	1647:1650	arg1	domain					1654:1659	the IgG ACPA V domain	1639:1659	the IgG ACPA V domain	1639:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	7	3	theme	ultra	1115:1119	arg1	analysis					1173:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis.
31067000	13	4	theme	predictive	1920:1929	arg1	marker					1931:1936	a predictive marker	1918:1936	a predictive marker for RA development	1918:1955	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	8	5	theme	data	1199:1202	arg1	sets					1204:1207	both data sets	1194:1207	both data sets	1194:1207	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	4	6	theme	glycans	642:648	arg1	presence					630:637	the presence	626:637	the presence of glycans in IgG ACPA V domains	626:670	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	10	7	theme	[95	1552:1554	arg1	interval					1568:1575	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	13	8	theme	IgG	1889:1891	arg1	domain					1900:1905	the IgG ACPA V domain	1885:1905	the IgG ACPA V domain	1885:1905	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	2	9	theme	IgG	269:271	arg1	ACPAs					273:277	IgG ACPAs	269:277	IgG ACPAs	269:277	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	8	10	theme	domain	1268:1273	arg1	glycans					1275:1281	V domain glycans	1266:1281	V domain glycans (<50%)	1266:1288	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	8	10	theme	domain	1268:1273	arg1	%					1287:1287	<50%	1284:1287	<50%	1284:1287	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	13	11	theme	V	1898:1898	arg1	domain					1900:1905	the IgG ACPA V domain	1885:1905	the IgG ACPA V domain	1885:1905	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	4	12	from	presence	630:637	arg1	domains					664:670	IgG ACPA V domains	653:670	IgG ACPA V domains	653:670	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	10	13	dep	=	1591:1591	arg1	interval					1568:1575	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	8	14	theme	IgG	1222:1224	arg1	ACPA					1226:1229	FDR-derived IgG ACPA	1210:1229	FDR-derived IgG ACPA	1210:1229	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	6	15	theme	cross-sectional	952:966	arg1	samples					985:991	cross-sectional and longitudinal samples	952:991	cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis	952:1056	Both sets originated from an Indigenous North American population and comprised cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis.
31067000	2	16	link	N-linked	286:293	arg1	glycans					295:301	N-linked glycans	286:301	N-linked glycans	286:301	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	0	17	theme	Arthritis	123:131	arg1	Development					97:107	the Development	93:107	the Development of Rheumatoid Arthritis	93:131	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	5	18	theme	ACPA-positive	812:824	arg1	FDRs					850:853	FDRs	850:853	FDRs	850:853	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	5	18	theme	ACPA-positive	812:824	arg1	relatives					839:847	126 ACPA-positive first-degree relatives	808:847	126 ACPA-positive first-degree relatives (FDRs) of RA patients	808:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	7	19	theme	Serum	1059:1063	arg1	ACPAs					1069:1073	Serum IgG ACPAs	1059:1073	Serum IgG ACPAs	1059:1073	Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis.
31067000	8	20	theme	lower	1250:1254	arg1	levels					1256:1261	markedly lower levels	1241:1261	markedly lower levels of V domain glycans (<50%)	1241:1288	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	6	21	theme	American	918:925	arg1	population					927:936	an Indigenous North American population	898:936	an Indigenous North American population	898:936	Both sets originated from an Indigenous North American population and comprised cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis.
31067000	6	22	theme	Indigenous	901:910	arg1	population					927:936	an Indigenous North American population	898:936	an Indigenous North American population	898:936	Both sets originated from an Indigenous North American population and comprised cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis.
31067000	8	23	theme	IgG	1302:1304	arg1	ACPA					1306:1309	IgG ACPA	1302:1309	IgG ACPA from RA patients	1302:1326	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	11	24	theme	Indigenous	1707:1716	arg1	patients					1736:1743	Indigenous North American RA patients	1707:1743	Indigenous North American RA patients	1707:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	1	25	theme	Anti-citrullinated	144:161	arg1	antibodies					171:180	OBJECTIVE Anti-citrullinated protein antibodies	134:180	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs)	134:188	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	25	theme	Anti-citrullinated	144:161	arg1	biomarkers					211:220	disease-specific biomarkers	194:220	disease-specific biomarkers in rheumatoid arthritis (RA)	194:249	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	25	theme	Anti-citrullinated	144:161	arg1	ACPAs					183:187	ACPAs	183:187	ACPAs	183:187	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	4	26	theme	predisease	701:710	arg1	autoimmunity					712:723	predisease autoimmunity	701:723	predisease autoimmunity	701:723	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	4	27	theme	V	662:662	arg1	domains					664:670	IgG ACPA V domains	653:670	IgG ACPA V domains	653:670	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	11	28	theme	FDRs	1699:1702	arg1	subset					1677:1682	a subset	1675:1682	a subset of predisposed FDRs of Indigenous North American RA patients	1675:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	0	29	theme	Anti-Citrullinated	47:64	arg1	Antibodies					74:83	IgG Anti-Citrullinated Protein Antibodies	43:83	IgG Anti-Citrullinated Protein Antibodies	43:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	13	30	theme	prevention	2017:2026	arg1	measures					2028:2035	prevention measures	2017:2035	prevention measures	2017:2035	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	5	31	theme	patients	862:869	arg1	FDRs					850:853	FDRs	850:853	FDRs	850:853	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	5	31	theme	patients	862:869	arg1	relatives					839:847	126 ACPA-positive first-degree relatives	808:847	126 ACPA-positive first-degree relatives (FDRs) of RA patients	808:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	11	32	theme	patients	1736:1743	arg1	FDRs					1699:1702	predisposed FDRs	1687:1702	predisposed FDRs of Indigenous North American RA patients	1687:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	0	33	theme	Antibodies	74:83	arg1	Antibodies					74:83	IgG Anti-Citrullinated Protein Antibodies	43:83	IgG Anti-Citrullinated Protein Antibodies	43:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	0	33	theme	Antibodies	74:83	arg1	Domain					33:38	the Variable Domain	20:38	the Variable Domain of IgG Anti-Citrullinated Protein Antibodies	20:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	11	34	theme	American	1724:1731	arg1	patients					1736:1743	Indigenous North American RA patients	1707:1743	Indigenous North American RA patients	1707:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	6	35	theme	longitudinal	972:983	arg1	samples					985:991	cross-sectional and longitudinal samples	952:991	cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis	952:1056	Both sets originated from an Indigenous North American population and comprised cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis.
31067000	11	36	from	present	1664:1670	arg1	subset					1677:1682	a subset	1675:1682	a subset of predisposed FDRs of Indigenous North American RA patients	1675:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	8	37	from	patients	1319:1326	arg1	ACPA					1306:1309	IgG ACPA	1302:1309	IgG ACPA from RA patients	1302:1326	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	10	38	theme	ACPA	1451:1454	arg1	glycosylation					1465:1477	IgG ACPA V-domain glycosylation	1447:1477	IgG ACPA V-domain glycosylation	1447:1477	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	3	39	theme	somatic	419:425	arg1	process					461:467	a T cell-dependent process	442:467	a T cell-dependent process	442:467	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	3	39	theme	somatic	419:425	arg1	hypermutation					427:439	somatic hypermutation	419:439	somatic hypermutation	419:439	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	0	40	theme	N-Linked	0:7	arg1	Glycans					9:15	N-Linked Glycans	0:15	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies	0:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	3	41	gly	N-glycosylation	358:372	arg2	sites					374:378	The corresponding N-glycosylation sites	340:378	The corresponding N-glycosylation sites in ACPA V-region sequences	340:405	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	3	42	theme	N-glycosylation	358:372	arg1	sites					374:378	The corresponding N-glycosylation sites	340:378	The corresponding N-glycosylation sites in ACPA V-region sequences	340:405	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	4	43	theme	ACPA	539:542	arg1	response					544:551	the ACPA response	535:551	the ACPA response prior to arthritis onset	535:576	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	11	44	located	present	1664:1670	arg1	subset					1677:1682	a subset	1675:1682	a subset of predisposed FDRs of Indigenous North American RA patients	1675:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	11	44	located	present	1664:1670	arg2	glycosylation					1622:1634	CONCLUSION Extensive glycosylation	1601:1634	CONCLUSION Extensive glycosylation of the IgG ACPA V domain	1601:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	6	45	theme	inflammatory	1035:1046	arg1	arthritis					1048:1056	inflammatory arthritis	1035:1056	inflammatory arthritis	1035:1056	Both sets originated from an Indigenous North American population and comprised cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis.
31067000	0	46	theme	Variable	24:31	arg1	Antibodies					74:83	IgG Anti-Citrullinated Protein Antibodies	43:83	IgG Anti-Citrullinated Protein Antibodies	43:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	0	46	theme	Variable	24:31	arg1	Domain					33:38	the Variable Domain	20:38	the Variable Domain of IgG Anti-Citrullinated Protein Antibodies	20:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	5	47	theme	independent	760:770	arg1	sets					772:775	2 independent sets	758:775	2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients	758:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	5	47	theme	independent	760:770	arg1	samples					786:792	serum samples	780:792	serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients	780:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	3	48	theme	V-region	388:395	arg1	sequences					397:405	ACPA V-region sequences	383:405	ACPA V-region sequences	383:405	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	10	49	theme	RA	1530:1531	arg1	development					1515:1525	future development	1508:1525	future development of RA	1508:1531	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	7	50	theme	glycan	1166:1171	arg1	analysis					1173:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis.
31067000	11	51	theme	predisposed	1687:1697	arg1	FDRs					1699:1702	predisposed FDRs	1687:1702	predisposed FDRs of Indigenous North American RA patients	1687:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	12	52	theme	RA	1811:1812	arg1	development					1814:1824	RA development	1811:1824	RA development	1811:1824	The presence of this feature substantially increases the risk of RA development.
31067000	10	53	theme	6.07	1547:1550	arg1	ratio					1541:1545	ratio	1541:1545	ratio	1541:1545	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	4	54	attach	presence	630:637	arg1	domains					664:670	IgG ACPA V domains	653:670	IgG ACPA V domains	653:670	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	4	54	attach	presence	630:637	arg2	glycans					642:648	glycans	642:648	glycans	642:648	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	13	55	theme	RA	1942:1943	arg1	development					1945:1955	RA development	1942:1955	RA development	1942:1955	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	9	56	theme	V-domain	1383:1390	arg1	glycosylation					1392:1404	extensive V-domain glycosylation	1373:1404	extensive V-domain glycosylation	1373:1404	Notably, FDRs who later developed RA showed extensive V-domain glycosylation before the onset of arthritis.
31067000	0	57	theme	IgG	43:45	arg1	Antibodies					74:83	IgG Anti-Citrullinated Protein Antibodies	43:83	IgG Anti-Citrullinated Protein Antibodies	43:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	10	58	theme	hazard	1534:1539	arg1	ratio					1541:1545	ratio	1541:1545	ratio	1541:1545	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	7	59	theme	high-performance	1121:1136	arg1	analysis					1173:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis.
31067000	4	60	theme	arthritis	562:570	arg1	onset					572:576	arthritis onset	562:576	arthritis onset	562:576	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	11	61	theme	Extensive	1612:1620	arg1	glycosylation					1622:1634	CONCLUSION Extensive glycosylation	1601:1634	CONCLUSION Extensive glycosylation of the IgG ACPA V domain	1601:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	2	62	theme	N-linked	286:293	arg1	glycans					295:301	N-linked glycans	286:301	N-linked glycans	286:301	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	10	63	theme	%	1555:1555	arg1	interval					1568:1575	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	hazard ratio 6.07 [95% confidence interval 1.46-25.2]	1534:1586	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	11	64	theme	V	1652:1652	arg1	domain					1654:1659	the IgG ACPA V domain	1639:1659	the IgG ACPA V domain	1639:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	2	65	theme	ACPAs	273:277	arg1	%					264:264	More than 90%	252:264	More than 90% of IgG ACPAs	252:277	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	2	65	theme	ACPAs	273:277	arg1	ACPAs					273:277	IgG ACPAs	269:277	IgG ACPAs	269:277	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	4	66	theme	IgG	653:655	arg1	domains					664:670	IgG ACPA V domains	653:670	IgG ACPA V domains	653:670	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	9	67	theme	arthritis	1426:1434	arg1	onset					1417:1421	the onset	1413:1421	the onset of arthritis	1413:1434	Notably, FDRs who later developed RA showed extensive V-domain glycosylation before the onset of arthritis.
31067000	11	68	theme	IgG	1643:1645	arg1	domain					1654:1659	the IgG ACPA V domain	1639:1659	the IgG ACPA V domain	1639:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	13	69	theme	ACPA	1893:1896	arg1	domain					1900:1905	the IgG ACPA V domain	1885:1905	the IgG ACPA V domain	1885:1905	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	2	70	theme	antibody	310:317	arg1	domain					332:337	the antibody variable (V) domain	306:337	the antibody variable (V) domain	306:337	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	1	71	theme	disease-specific	194:209	arg1	antibodies					171:180	OBJECTIVE Anti-citrullinated protein antibodies	134:180	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs)	134:188	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	71	theme	disease-specific	194:209	arg1	biomarkers					211:220	disease-specific biomarkers	194:220	disease-specific biomarkers in rheumatoid arthritis (RA)	194:249	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	8	72	theme	V	1266:1266	arg1	glycans					1275:1281	V domain glycans	1266:1281	V domain glycans (<50%)	1266:1288	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	8	72	theme	V	1266:1266	arg1	%					1287:1287	<50%	1284:1287	<50%	1284:1287	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	7	73	theme	IgG	1065:1067	arg1	ACPAs					1069:1073	Serum IgG ACPAs	1059:1073	Serum IgG ACPAs	1059:1073	Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis.
31067000	13	74	theme	domain	1900:1905	arg1	glycosylation					1868:1880	glycosylation	1868:1880	glycosylation of the IgG ACPA V domain	1868:1905	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	11	75	attach	present	1664:1670	arg1	subset					1677:1682	a subset	1675:1682	a subset of predisposed FDRs of Indigenous North American RA patients	1675:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	11	75	attach	present	1664:1670	arg2	glycosylation					1622:1634	CONCLUSION Extensive glycosylation	1601:1634	CONCLUSION Extensive glycosylation of the IgG ACPA V domain	1601:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	8	76	theme	FDR-derived	1210:1220	arg1	ACPA					1226:1229	FDR-derived IgG ACPA	1210:1229	FDR-derived IgG ACPA	1210:1229	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	8	77	theme	glycans	1275:1281	arg1	levels					1256:1261	markedly lower levels	1241:1261	markedly lower levels of V domain glycans (<50%)	1241:1288	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	11	78	gly	glycosylation	1622:1634	arg1	domain					1654:1659	the IgG ACPA V domain	1639:1659	the IgG ACPA V domain	1639:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	11	78	gly	glycosylation	1622:1634	arg2	subset					1677:1682	a subset	1675:1682	a subset of predisposed FDRs of Indigenous North American RA patients	1675:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	5	79	theme	first-degree	826:837	arg1	FDRs					850:853	FDRs	850:853	FDRs	850:853	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	5	79	theme	first-degree	826:837	arg1	relatives					839:847	126 ACPA-positive first-degree relatives	808:847	126 ACPA-positive first-degree relatives (FDRs) of RA patients	808:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	5	80	dep	METHODS	738:744	arg1	analyzed					749:756	analyzed	749:756	analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients	749:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	1	81	theme	OBJECTIVE	134:142	arg1	antibodies					171:180	OBJECTIVE Anti-citrullinated protein antibodies	134:180	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs)	134:188	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	81	theme	OBJECTIVE	134:142	arg1	biomarkers					211:220	disease-specific biomarkers	194:220	disease-specific biomarkers in rheumatoid arthritis (RA)	194:249	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	81	theme	OBJECTIVE	134:142	arg1	ACPAs					183:187	ACPAs	183:187	ACPAs	183:187	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	0	82	theme	Protein	66:72	arg1	Antibodies					74:83	IgG Anti-Citrullinated Protein Antibodies	43:83	IgG Anti-Citrullinated Protein Antibodies	43:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	1	83	from	biomarkers	211:220	arg1	RA					247:248	RA	247:248	RA	247:248	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	83	from	biomarkers	211:220	arg1	arthritis					236:244	rheumatoid arthritis	225:244	rheumatoid arthritis (RA)	225:249	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	5	84	theme	RA	859:860	arg1	patients					862:869	RA patients	859:869	RA patients	859:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	11	85	from	subset	1677:1682	arg1	present					1664:1670	present	1664:1670	present	1664:1670	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	4	86	theme	T	503:503	arg1	cells					505:509	T cells	503:509	T cells	503:509	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	4	87	theme	ACPA	657:660	arg1	domains					664:670	IgG ACPA V domains	653:670	IgG ACPA V domains	653:670	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	13	88	gly	glycosylation	1868:1880	arg1	domain					1900:1905	the IgG ACPA V domain	1885:1905	the IgG ACPA V domain	1885:1905	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	6	89	theme	individuals	996:1006	arg1	samples					985:991	cross-sectional and longitudinal samples	952:991	cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis	952:1056	Both sets originated from an Indigenous North American population and comprised cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis.
31067000	0	90	from	Glycans	9:15	arg1	Antibodies					74:83	IgG Anti-Citrullinated Protein Antibodies	43:83	IgG Anti-Citrullinated Protein Antibodies	43:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	0	90	from	Glycans	9:15	arg1	Domain					33:38	the Variable Domain	20:38	the Variable Domain of IgG Anti-Citrullinated Protein Antibodies	20:83	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	8	91	theme	RA	1316:1317	arg1	patients					1319:1326	RA patients	1316:1326	RA patients	1316:1326	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	8	92	link	FDR-derived	1210:1220	arg1	ACPA					1226:1229	FDR-derived IgG ACPA	1210:1229	FDR-derived IgG ACPA	1210:1229	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	3	93	theme	corresponding	344:356	arg1	sites					374:378	The corresponding N-glycosylation sites	340:378	The corresponding N-glycosylation sites in ACPA V-region sequences	340:405	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	4	94	theme	ample	473:477	arg1	evidence					479:486	ample evidence	473:486	ample evidence	473:486	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	8	95	dep	RESULTS	1183:1189	arg1	displayed					1231:1239	displayed	1231:1239	displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients	1231:1326	RESULTS In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients.
31067000	11	96	theme	RA	1733:1734	arg1	patients					1736:1743	Indigenous North American RA patients	1707:1743	Indigenous North American RA patients	1707:1743	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	0	97	theme	Rheumatoid	112:121	arg1	Arthritis					123:131	Rheumatoid Arthritis	112:131	Rheumatoid Arthritis	112:131	N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis.
31067000	3	98	from	sites	374:378	arg1	sequences					397:405	ACPA V-region sequences	383:405	ACPA V-region sequences	383:405	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	1	99	theme	rheumatoid	225:234	arg1	RA					247:248	RA	247:248	RA	247:248	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	99	theme	rheumatoid	225:234	arg1	arthritis					236:244	rheumatoid arthritis	225:244	rheumatoid arthritis (RA)	225:249	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	10	100	theme	V-domain	1456:1463	arg1	glycosylation					1465:1477	IgG ACPA V-domain glycosylation	1447:1477	IgG ACPA V-domain glycosylation	1447:1477	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	5	101	theme	serum	780:784	arg1	samples					786:792	serum samples	780:792	serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients	780:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	3	102	theme	ACPA	383:386	arg1	sequences					397:405	ACPA V-region sequences	383:405	ACPA V-region sequences	383:405	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	4	103	theme	response	544:551	arg1	maturation					521:530	the maturation	517:530	the maturation of the ACPA response prior to arthritis onset	517:576	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	10	104	theme	IgG	1447:1449	arg1	glycosylation					1465:1477	IgG ACPA V-domain glycosylation	1447:1477	IgG ACPA V-domain glycosylation	1447:1477	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	5	105	theme	samples	786:792	arg1	sets					772:775	2 independent sets	758:775	2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients	758:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	5	105	theme	samples	786:792	arg1	samples					786:792	serum samples	780:792	serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients	780:869	METHODS We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients.
31067000	4	106	from	autoimmunity	712:723	arg1	transition					685:694	the transition	681:694	the transition from predisease autoimmunity to overt RA	681:735	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	4	107	theme	overt	728:732	arg1	RA					734:735	overt RA	728:735	overt RA	728:735	As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA.
31067000	11	108	theme	domain	1654:1659	arg1	glycosylation					1622:1634	CONCLUSION Extensive glycosylation	1601:1634	CONCLUSION Extensive glycosylation of the IgG ACPA V domain	1601:1659	CONCLUSION Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients.
31067000	13	109	theme	ACPA-positive	1960:1972	arg1	individuals					1974:1984	ACPA-positive individuals	1960:1984	ACPA-positive individuals	1960:1984	Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
31067000	3	110	theme	cell-dependent	446:459	arg1	process					461:467	a T cell-dependent process	442:467	a T cell-dependent process	442:467	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	3	110	theme	cell-dependent	446:459	arg1	hypermutation					427:439	somatic hypermutation	419:439	somatic hypermutation	419:439	The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process.
31067000	7	111	theme	chromatography-based	1145:1164	arg1	analysis					1173:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	ultra high-performance liquid chromatography-based glycan analysis	1115:1180	Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis.
31067000	12	112	theme	feature	1767:1773	arg1	presence					1750:1757	The presence	1746:1757	The presence of this feature	1746:1773	The presence of this feature substantially increases the risk of RA development.
31067000	2	113	theme	V	329:329	arg1	domain					332:337	the antibody variable (V) domain	306:337	the antibody variable (V) domain	306:337	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	12	114	theme	development	1814:1824	arg1	risk					1803:1806	the risk	1799:1806	the risk of RA development	1799:1824	The presence of this feature substantially increases the risk of RA development.
31067000	1	115	theme	protein	163:169	arg1	antibodies					171:180	OBJECTIVE Anti-citrullinated protein antibodies	134:180	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs)	134:188	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	115	theme	protein	163:169	arg1	biomarkers					211:220	disease-specific biomarkers	194:220	disease-specific biomarkers in rheumatoid arthritis (RA)	194:249	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	1	115	theme	protein	163:169	arg1	ACPAs					183:187	ACPAs	183:187	ACPAs	183:187	OBJECTIVE Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA).
31067000	10	116	theme	future	1508:1513	arg1	development					1515:1525	future development	1508:1525	future development of RA	1508:1531	Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013).
31067000	2	117	theme	variable	319:326	arg1	domain					332:337	the antibody variable (V) domain	306:337	the antibody variable (V) domain	306:337	More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain.
31067000	9	118	theme	extensive	1373:1381	arg1	glycosylation					1392:1404	extensive V-domain glycosylation	1373:1404	extensive V-domain glycosylation	1373:1404	Notably, FDRs who later developed RA showed extensive V-domain glycosylation before the onset of arthritis.
31545463	5	0	theme	O‑GlcNAc	969:976	arg1	modification					978:989	endometrial O‑GlcNAc modification	957:989	endometrial O‑GlcNAc modification	957:989	Additionally, the level of endometrial O‑GlcNAc modification increased gradually from the pre‑receptive to the receptive phase, which was then decreased during the non‑receptive phase.
31545463	5	1	theme	receptive	1041:1049	arg1	phase					1051:1055	the receptive phase	1037:1055	the receptive phase	1037:1055	Additionally, the level of endometrial O‑GlcNAc modification increased gradually from the pre‑receptive to the receptive phase, which was then decreased during the non‑receptive phase.
31545463	1	2	theme	dynamic	186:192	arg1	process					226:232	a dynamic post‑translational modification process	184:232	a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling	184:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	2	theme	dynamic	186:192	arg1	modification					168:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	3	theme	cell	299:302	arg1	regulation					310:319	cell cycle regulation	299:319	cell cycle regulation	299:319	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	8	4	theme	receptivity	1612:1622	arg1	regulation					1586:1595	the regulation	1582:1595	the regulation of endometrial receptivity and embryo implantation	1582:1646	It is hypothesized that O‑GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation.
31545463	5	5	theme	endometrial	957:967	arg1	modification					978:989	endometrial O‑GlcNAc modification	957:989	endometrial O‑GlcNAc modification	957:989	Additionally, the level of endometrial O‑GlcNAc modification increased gradually from the pre‑receptive to the receptive phase, which was then decreased during the non‑receptive phase.
31545463	1	6	theme	O‑linked	126:133	arg1	O‑GlcNAc					158:165	O‑GlcNAc	158:165	O‑GlcNAc	158:165	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	6	theme	O‑linked	126:133	arg1	β‑N‑acetylglucosamine					135:155	O‑linked β‑N‑acetylglucosamine	126:155	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	7	theme	cycle	304:308	arg1	regulation					310:319	cell cycle regulation	299:319	cell cycle regulation	299:319	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	9	8	contain	have	1686:1689	arg2	implications					1701:1712	important implications	1691:1712	important implications for the understanding of female fertility	1691:1754	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	9	8	contain	have	1686:1689	arg1	results					1653:1659	The results	1649:1659	The results of the present study	1649:1680	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	8	9	theme	implantation	1635:1646	arg1	regulation					1586:1595	the regulation	1582:1595	the regulation of endometrial receptivity and embryo implantation	1582:1646	It is hypothesized that O‑GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation.
31545463	9	10	theme	infertility	1777:1787	arg1	treatments					1789:1798	infertility treatments	1777:1798	infertility treatments	1777:1798	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	4	11	from	expression	721:730	arg1	endometrium					785:795	the human secretory endometrium	765:795	the human secretory endometrium	765:795	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	4	12	theme	secretory	775:783	arg1	endometrium					785:795	the human secretory endometrium	765:795	the human secretory endometrium	765:795	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	4	13	theme	proteins	753:760	arg1	higher					801:806	higher	801:806	higher	801:806	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	4	13	theme	proteins	753:760	arg1	expression					721:730	the expression	717:730	the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium	717:795	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	4	14	theme	human	769:773	arg1	endometrium					785:795	the human secretory endometrium	765:795	the human secretory endometrium	765:795	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	7	15	theme	modification	1389:1400	arg1	level					1371:1375	the level	1367:1375	the level of O‑GlcNAc modification	1367:1400	The results revealed that increasing the level of O‑GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation.
31545463	1	16	theme	post‑translational	194:211	arg1	process					226:232	a dynamic post‑translational modification process	184:232	a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling	184:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	16	theme	post‑translational	194:211	arg1	modification					168:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	5	17	theme	modification	978:989	arg1	level					948:952	the level	944:952	the level of endometrial O‑GlcNAc modification	944:989	Additionally, the level of endometrial O‑GlcNAc modification increased gradually from the pre‑receptive to the receptive phase, which was then decreased during the non‑receptive phase.
31545463	9	18	theme	present	1668:1674	arg1	study					1676:1680	the present study	1664:1680	the present study	1664:1680	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	1	19	theme	modification	213:224	arg1	process					226:232	a dynamic post‑translational modification process	184:232	a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling	184:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	19	theme	modification	213:224	arg1	modification					168:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	9	20	theme	study	1676:1680	arg1	results					1653:1659	The results	1649:1659	The results of the present study	1649:1680	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	8	21	theme	embryo	1628:1633	arg1	implantation					1635:1646	embryo implantation	1628:1646	embryo implantation	1628:1646	It is hypothesized that O‑GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation.
31545463	0	22	theme	O‑GlcNAc	0:7	arg1	modification					9:20	O‑GlcNAc modification	0:20	O‑GlcNAc modification	0:20	O‑GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.
31545463	3	23	theme	O‑GlcNAcylation	592:606	arg1	role					584:587	the role	580:587	the role of O‑GlcNAcylation	580:606	The present study aimed to determine the role of O‑GlcNAcylation during embryo implantation by inhibiting or enhancing its function and expression.
31545463	6	24	theme	modification	1316:1327	arg1	levels					1297:1302	levels	1297:1302	levels of O‑GlcNAc modification	1297:1327	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	25	used	utilized	1158:1165	arg2	interference					1141:1152	RNA interference	1137:1152	RNA interference	1137:1152	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	3	26	theme	embryo	615:620	arg1	implantation					622:633	embryo implantation	615:633	embryo implantation	615:633	The present study aimed to determine the role of O‑GlcNAcylation during embryo implantation by inhibiting or enhancing its function and expression.
31545463	7	27	theme	cellular	1411:1418	arg1	proliferation					1420:1432	proliferation	1420:1432	proliferation	1420:1432	The results revealed that increasing the level of O‑GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation.
31545463	0	28	theme	endometrial	33:43	arg1	receptivity					45:55	endometrial receptivity	33:55	endometrial receptivity	33:55	O‑GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.
31545463	1	29	theme	nutrient	322:329	arg1	metabolism					331:340	nutrient metabolism	322:340	nutrient metabolism	322:340	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	6	30	theme	decomposition	1226:1238	arg1	enzymes					1240:1246	two key O‑GlcNAc synthesis and decomposition enzymes	1195:1246	two key O‑GlcNAc synthesis and decomposition enzymes	1195:1246	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	30	theme	decomposition	1226:1238	arg1	OGA					1257:1259	OGA	1257:1259	OGA	1257:1259	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	30	theme	decomposition	1226:1238	arg1	OGT					1249:1251	OGT	1249:1251	OGT	1249:1251	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	31	theme	O‑GlcNAc	1307:1314	arg1	modification					1316:1327	O‑GlcNAc modification	1307:1327	O‑GlcNAc modification	1307:1327	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	2	32	theme	O‑GlcNAc	479:486	arg1	OGT					501:503	OGT	501:503	OGT	501:503	This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively.
31545463	2	32	theme	O‑GlcNAc	479:486	arg1	transferase 					488:499	O‑GlcNAc transferase 	479:499	O‑GlcNAc transferase (OGT)	479:504	This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively.
31545463	6	33	theme	enzymes	1240:1246	arg1	expression					1181:1190	the expression	1177:1190	the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification	1177:1327	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	0	34	dep	cell	82:85	arg1	invasion					116:123	invasion	116:123	invasion	116:123	O‑GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.
31545463	0	34	dep	cell	82:85	arg1	migration					102:110	migration	102:110	migration	102:110	O‑GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.
31545463	0	34	dep	cell	82:85	arg1	proliferation					87:99	proliferation	87:99	proliferation	87:99	O‑GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.
31545463	4	35	theme	O‑GlcNAc‑modified	735:751	arg1	proteins					753:760	O‑GlcNAc‑modified proteins	735:760	O‑GlcNAc‑modified proteins	735:760	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	5	36	theme	non‑receptive	1094:1106	arg1	phase					1108:1112	the non‑receptive phase	1090:1112	the non‑receptive phase	1090:1112	Additionally, the level of endometrial O‑GlcNAc modification increased gradually from the pre‑receptive to the receptive phase, which was then decreased during the non‑receptive phase.
31545463	9	37	theme	fertility	1746:1754	arg1	understanding					1722:1734	the understanding	1718:1734	the understanding of female fertility	1718:1754	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	1	38	theme	extracellular	346:358	arg1	signaling					360:368	extracellular signaling	346:368	extracellular signaling	346:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	8	39	theme	important	1564:1572	arg1	role					1574:1577	an important role	1561:1577	an important role	1561:1577	It is hypothesized that O‑GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation.
31545463	1	40	theme	many	254:257	arg1	processes					278:286	many crucial biological processes	254:286	many crucial biological processes	254:286	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	40	theme	many	254:257	arg1	metabolism					331:340	nutrient metabolism	322:340	nutrient metabolism	322:340	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	40	theme	many	254:257	arg1	signaling					360:368	extracellular signaling	346:368	extracellular signaling	346:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	40	theme	many	254:257	arg1	regulation					310:319	cell cycle regulation	299:319	cell cycle regulation	299:319	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	0	41	theme	endometrial	70:80	arg1	cell					82:85	endometrial cell proliferation, migration and invasion	70:123	endometrial cell proliferation, migration and invasion	70:123	O‑GlcNAc modification influences endometrial receptivity by promoting endometrial cell proliferation, migration and invasion.
31545463	4	42	theme	western	887:893	arg1	blotting					895:902	western blotting	887:902	western blotting	887:902	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	1	43	theme	β‑N‑acetylglucosamine	135:155	arg1	process					226:232	a dynamic post‑translational modification process	184:232	a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling	184:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	43	theme	β‑N‑acetylglucosamine	135:155	arg1	modification					168:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	3	44	theme	present	547:553	arg1	study					555:559	The present study	543:559	The present study	543:559	The present study aimed to determine the role of O‑GlcNAcylation during embryo implantation by inhibiting or enhancing its function and expression.
31545463	6	45	theme	O‑GlcNAc	1203:1210	arg1	synthesis					1212:1220	O‑GlcNAc synthesis	1203:1220	O‑GlcNAc synthesis	1203:1220	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	4	46	theme	proliferative	848:860	arg1	phase					862:866	the proliferative phase	844:866	the proliferative phase	844:866	The results revealed that the expression of O‑GlcNAc‑modified proteins in the human secretory endometrium was higher than that of the endometrium during the proliferative phase, as determined via western blotting and immunohistochemistry.
31545463	6	47	theme	key	1199:1201	arg1	enzymes					1240:1246	two key O‑GlcNAc synthesis and decomposition enzymes	1195:1246	two key O‑GlcNAc synthesis and decomposition enzymes	1195:1246	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	47	theme	key	1199:1201	arg1	OGA					1257:1259	OGA	1257:1259	OGA	1257:1259	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	47	theme	key	1199:1201	arg1	OGT					1249:1251	OGT	1249:1251	OGT	1249:1251	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	7	48	theme	embryo	1487:1492	arg1	implantation					1494:1505	embryo implantation	1487:1505	embryo implantation	1487:1505	The results revealed that increasing the level of O‑GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation.
31545463	1	49	theme	crucial	259:265	arg1	processes					278:286	many crucial biological processes	254:286	many crucial biological processes	254:286	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	49	theme	crucial	259:265	arg1	metabolism					331:340	nutrient metabolism	322:340	nutrient metabolism	322:340	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	49	theme	crucial	259:265	arg1	signaling					360:368	extracellular signaling	346:368	extracellular signaling	346:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	49	theme	crucial	259:265	arg1	regulation					310:319	cell cycle regulation	299:319	cell cycle regulation	299:319	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	9	50	theme	female	1739:1744	arg1	fertility					1746:1754	female fertility	1739:1754	female fertility	1739:1754	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	2	51	theme	dynamic	376:382	arg1	modification					384:395	This dynamic modification	371:395	This dynamic modification	371:395	This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively.
31545463	6	52	theme	synthesis	1212:1220	arg1	enzymes					1240:1246	two key O‑GlcNAc synthesis and decomposition enzymes	1195:1246	two key O‑GlcNAc synthesis and decomposition enzymes	1195:1246	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	52	theme	synthesis	1212:1220	arg1	OGA					1257:1259	OGA	1257:1259	OGA	1257:1259	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	6	52	theme	synthesis	1212:1220	arg1	OGT					1249:1251	OGT	1249:1251	OGT	1249:1251	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	1	53	theme	biological	267:276	arg1	processes					278:286	many crucial biological processes	254:286	many crucial biological processes	254:286	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	53	theme	biological	267:276	arg1	metabolism					331:340	nutrient metabolism	322:340	nutrient metabolism	322:340	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	53	theme	biological	267:276	arg1	signaling					360:368	extracellular signaling	346:368	extracellular signaling	346:368	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	53	theme	biological	267:276	arg1	regulation					310:319	cell cycle regulation	299:319	cell cycle regulation	299:319	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	6	54	theme	endometrial	1118:1128	arg1	cells					1130:1134	endometrial cells	1118:1134	endometrial cells	1118:1134	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	8	55	theme	O‑GlcNAc	1532:1539	arg1	modification					1541:1552	O‑GlcNAc modification	1532:1552	O‑GlcNAc modification	1532:1552	It is hypothesized that O‑GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation.
31545463	6	56	theme	RNA	1137:1139	arg1	interference					1141:1152	RNA interference	1137:1152	RNA interference	1137:1152	In endometrial cells, RNA interference was utilized to reduce the expression of two key O‑GlcNAc synthesis and decomposition enzymes, OGT and OGA, to indirectly increase or decrease levels of O‑GlcNAc modification.
31545463	2	57	theme	glucose	425:431	arg1	concentration					433:445	the ambient glucose concentration	413:445	the ambient glucose concentration	413:445	This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively.
31545463	7	58	theme	O‑GlcNAc	1380:1387	arg1	modification					1389:1400	O‑GlcNAc modification	1380:1400	O‑GlcNAc modification	1380:1400	The results revealed that increasing the level of O‑GlcNAc modification enhanced cellular proliferation, migration, invasion and adhesion, thereby promoting embryo implantation.
31545463	9	59	theme	important	1691:1699	arg1	implications					1701:1712	important implications	1691:1712	important implications for the understanding of female fertility	1691:1754	The results of the present study may have important implications for the understanding of female fertility and may help improve infertility treatments.
31545463	1	60	link	O‑linked	126:133	arg1	O‑GlcNAc					158:165	O‑GlcNAc	158:165	O‑GlcNAc	158:165	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	1	60	link	O‑linked	126:133	arg1	β‑N‑acetylglucosamine					135:155	O‑linked β‑N‑acetylglucosamine	126:155	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	126:179	O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification is a dynamic post‑translational modification process that is involved in many crucial biological processes, including cell cycle regulation, nutrient metabolism and extracellular signaling.
31545463	8	61	theme	endometrial	1600:1610	arg1	receptivity					1612:1622	endometrial receptivity	1600:1622	endometrial receptivity	1600:1622	It is hypothesized that O‑GlcNAc modification serves an important role in the regulation of endometrial receptivity and embryo implantation.
31545463	2	62	theme	ambient	417:423	arg1	concentration					433:445	the ambient glucose concentration	413:445	the ambient glucose concentration	413:445	This dynamic modification is dependent on the ambient glucose concentration and is catalyzed and removed by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA), respectively.
31489252	3	0	theme	cycle	306:310	arg1	arrest					312:317	cell cycle arrest	301:317	cell cycle arrest	301:317	Metformin induces cell cycle arrest in cancer cells, but the underlying mechanism remains unclear in cervical cancer system.
31489252	9	1	theme	HeLa	1646:1649	arg1	cells					1651:1655	HeLa cells	1646:1655	HeLa cells	1646:1655	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	5	2	theme	blot	514:517	arg1	analysis					519:526	Western blot analysis	506:526	Western blot analysis	506:526	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	6	3	used	used	747:750	arg2	analysis					734:741	Immunoprecipitation analysis	714:741	Immunoprecipitation analysis	714:741	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	7	4	theme	apoptotic	1055:1063	arg1	death					1070:1074	apoptotic cell death	1055:1074	apoptotic cell death	1055:1074	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	7	5	from	death	1070:1074	arg1	cells					1084:1088	HeLa cells	1079:1088	HeLa cells	1079:1088	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	10	6	theme	cervical	1772:1779	arg1	cells					1788:1792	cervical cancer cells	1772:1792	cervical cancer cells	1772:1792	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	4	7	theme	cancer	492:497	arg1	cells					499:503	cervical cancer cells	483:503	cervical cancer cells	483:503	Here, we examined how metformin affects cell cycle arrest and apoptosis in cervical cancer cells.
31489252	9	8	theme	increased	1601:1609	arg1	arrest					1622:1627	increased cell cycle arrest	1601:1627	increased cell cycle arrest	1601:1627	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	1	9	theme	diabetes	150:157	arg1	treatment					130:138	the treatment	126:138	the treatment of type 2 diabetes	126:157	Metformin is a widely used drug for the treatment of type 2 diabetes.
31489252	5	10	theme	metformin	693:701	arg1	treatment					703:711	metformin treatment	693:711	metformin treatment	693:711	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	4	11	theme	cervical	483:490	arg1	cells					499:503	cervical cancer cells	483:503	cervical cancer cells	483:503	Here, we examined how metformin affects cell cycle arrest and apoptosis in cervical cancer cells.
31489252	7	12	theme	flow	1103:1106	arg1	cytometry					1108:1116	flow cytometry	1103:1116	flow cytometry	1103:1116	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	10	13	theme	potential	1800:1808	arg1	benefit					1822:1828	potential therapeutic benefit	1800:1828	potential therapeutic benefit	1800:1828	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	8	14	theme	O-GlcNAc	1400:1407	arg1	modification					1409:1420	O-GlcNAc modification	1400:1420	O-GlcNAc modification	1400:1420	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	15	theme	fructose-6-phosphate	1169:1188	arg1	6-diazo-5-oxo-L-norleucine					1129:1154	6-diazo-5-oxo-L-norleucine	1129:1154	6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor)	1129:1216	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	15	theme	fructose-6-phosphate	1169:1188	arg1	inhibitor					1207:1215	a glutamine fructose-6-phosphate aminotransferase inhibitor	1157:1215	a glutamine fructose-6-phosphate aminotransferase inhibitor	1157:1215	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	16	theme	glutamine	1159:1167	arg1	6-diazo-5-oxo-L-norleucine					1129:1154	6-diazo-5-oxo-L-norleucine	1129:1154	6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor)	1129:1216	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	16	theme	glutamine	1159:1167	arg1	inhibitor					1207:1215	a glutamine fructose-6-phosphate aminotransferase inhibitor	1157:1215	a glutamine fructose-6-phosphate aminotransferase inhibitor	1157:1215	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	4	17	theme	cycle	453:457	arg1	arrest					459:464	cell cycle arrest	448:464	cell cycle arrest	448:464	Here, we examined how metformin affects cell cycle arrest and apoptosis in cervical cancer cells.
31489252	4	18	from	apoptosis	470:478	arg1	cells					499:503	cervical cancer cells	483:503	cervical cancer cells	483:503	Here, we examined how metformin affects cell cycle arrest and apoptosis in cervical cancer cells.
31489252	8	19	theme	AMPK	1364:1367	arg1	levels					1339:1344	levels	1339:1344	levels of phosphorylated AMPK	1339:1367	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	9	20	from	apoptosis	1633:1641	arg1	cells					1651:1655	HeLa cells	1646:1655	HeLa cells	1646:1655	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	4	21	theme	cell	448:451	arg1	arrest					459:464	cell cycle arrest	448:464	cell cycle arrest	448:464	Here, we examined how metformin affects cell cycle arrest and apoptosis in cervical cancer cells.
31489252	5	22	theme	transferase	603:613	arg1	levels					540:545	levels	540:545	levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT)	540:619	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	5	23	theme	O-GlcNAc	594:601	arg1	OGT					616:618	OGT	616:618	OGT	616:618	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	5	23	theme	O-GlcNAc	594:601	arg1	transferase					603:613	O-GlcNAc transferase	594:613	O-GlcNAc transferase (OGT)	594:619	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	9	24	theme	cell	1566:1569	arg1	p27					1536:1538	p27	1536:1538	p27	1536:1538	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	24	theme	cell	1566:1569	arg1	p21					1528:1530	p21	1528:1530	p21	1528:1530	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	24	theme	cell	1566:1569	arg1	inhibitors					1577:1586	AMPK-dependent cell cycle inhibitors	1551:1586	AMPK-dependent cell cycle inhibitors	1551:1586	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	8	25	theme	thiamet	1221:1227	arg1	G					1229:1229	thiamet G	1221:1229	thiamet G (an O-GlcNAcase inhibitor)	1221:1256	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	25	theme	thiamet	1221:1227	arg1	inhibitor					1247:1255	an O-GlcNAcase inhibitor	1232:1255	an O-GlcNAcase inhibitor	1232:1255	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	26	theme	phosphorylated	1349:1362	arg1	AMPK					1364:1367	phosphorylated AMPK	1349:1367	phosphorylated AMPK	1349:1367	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	27	theme	O-GlcNAcase	1235:1245	arg1	G					1229:1229	thiamet G	1221:1229	thiamet G (an O-GlcNAcase inhibitor)	1221:1256	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	27	theme	O-GlcNAcase	1235:1245	arg1	inhibitor					1247:1255	an O-GlcNAcase inhibitor	1232:1255	an O-GlcNAcase inhibitor	1232:1255	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	6	28	theme	protein	900:906	arg1	kinase					908:913	O-GlcNAcylated AMP-activated protein kinase	871:913	O-GlcNAcylated AMP-activated protein kinase (AMPK)	871:920	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	6	28	theme	protein	900:906	arg1	AMPK					916:919	AMPK	916:919	AMPK	916:919	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	4	29	from	arrest	459:464	arg1	cells					499:503	cervical cancer cells	483:503	cervical cancer cells	483:503	Here, we examined how metformin affects cell cycle arrest and apoptosis in cervical cancer cells.
31489252	9	30	theme	cycle	1571:1575	arg1	p27					1536:1538	p27	1536:1538	p27	1536:1538	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	30	theme	cycle	1571:1575	arg1	p21					1528:1530	p21	1528:1530	p21	1528:1530	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	30	theme	cycle	1571:1575	arg1	inhibitors					1577:1586	AMPK-dependent cell cycle inhibitors	1551:1586	AMPK-dependent cell cycle inhibitors	1551:1586	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	8	31	theme	O-GlcNAcylated	1291:1304	arg1	AMPK					1306:1309	O-GlcNAcylated AMPK	1291:1309	O-GlcNAcylated AMPK	1291:1309	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	6	32	theme	AMP-activated	886:898	arg1	kinase					908:913	O-GlcNAcylated AMP-activated protein kinase	871:913	O-GlcNAcylated AMP-activated protein kinase (AMPK)	871:920	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	6	32	theme	AMP-activated	886:898	arg1	AMPK					916:919	AMPK	916:919	AMPK	916:919	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	5	33	theme	O-linked	550:557	arg1	N-acetylglucosamine					559:577	O-linked N-acetylglucosamine	550:577	O-linked N-acetylglucosamine (O-GlcNAc)	550:588	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	5	33	theme	O-linked	550:557	arg1	O-GlcNAc					580:587	O-GlcNAc	580:587	O-GlcNAc	580:587	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	7	34	theme	cell	1065:1068	arg1	death					1070:1074	apoptotic cell death	1055:1074	apoptotic cell death	1055:1074	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	9	35	theme	metformin	1470:1478	arg1	treatment					1480:1488	metformin treatment	1470:1488	metformin treatment of HeLa cells	1470:1502	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	5	36	theme	N-acetylglucosamine	559:577	arg1	levels					540:545	levels	540:545	levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT)	540:619	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	9	37	theme	untreated	1669:1677	arg1	cells					1679:1683	untreated cells	1669:1683	untreated cells	1669:1683	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	38	theme	p27	1536:1538	arg1	levels					1518:1523	the levels	1514:1523	the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors)	1514:1587	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	3	39	theme	underlying	344:353	arg1	mechanism					355:363	the underlying mechanism	340:363	the underlying mechanism	340:363	Metformin induces cell cycle arrest in cancer cells, but the underlying mechanism remains unclear in cervical cancer system.
31489252	8	40	theme	aminotransferase	1190:1205	arg1	6-diazo-5-oxo-L-norleucine					1129:1154	6-diazo-5-oxo-L-norleucine	1129:1154	6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor)	1129:1216	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	40	theme	aminotransferase	1190:1205	arg1	inhibitor					1207:1215	a glutamine fructose-6-phosphate aminotransferase inhibitor	1157:1215	a glutamine fructose-6-phosphate aminotransferase inhibitor	1157:1215	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	7	41	theme	HeLa	1079:1082	arg1	cells					1084:1088	HeLa cells	1079:1088	HeLa cells	1079:1088	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	9	42	theme	cycle	1616:1620	arg1	arrest					1622:1627	increased cell cycle arrest	1601:1627	increased cell cycle arrest	1601:1627	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	10	43	theme	cancer	1781:1786	arg1	cells					1788:1792	cervical cancer cells	1772:1792	cervical cancer cells	1772:1792	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	0	44	theme	cervical	19:26	arg1	proliferation					40:52	cervical cancer cell proliferation	19:52	cervical cancer cell proliferation	19:52	Metformin inhibits cervical cancer cell proliferation via decreased AMPK O-GlcNAcylation.
31489252	6	45	theme	untreated	971:979	arg1	cells					981:985	untreated cells	971:985	untreated cells	971:985	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	6	46	theme	O-GlcNAcylated	871:884	arg1	kinase					908:913	O-GlcNAcylated AMP-activated protein kinase	871:913	O-GlcNAcylated AMP-activated protein kinase (AMPK)	871:920	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	6	46	theme	O-GlcNAcylated	871:884	arg1	AMPK					916:919	AMPK	916:919	AMPK	916:919	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	1	47	theme	used	112:115	arg1	drug					117:120	a widely used drug	103:120	a widely used drug for the treatment of type 2 diabetes	103:157	Metformin is a widely used drug for the treatment of type 2 diabetes.
31489252	1	47	theme	used	112:115	arg1	Metformin					90:98	Metformin	90:98	Metformin	90:98	Metformin is a widely used drug for the treatment of type 2 diabetes.
31489252	9	48	theme	HeLa	1493:1496	arg1	cells					1498:1502	HeLa cells	1493:1502	HeLa cells	1493:1502	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	3	49	theme	cancer	393:398	arg1	system					400:405	cervical cancer system	384:405	cervical cancer system	384:405	Metformin induces cell cycle arrest in cancer cells, but the underlying mechanism remains unclear in cervical cancer system.
31489252	9	50	theme	cells	1498:1502	arg1	treatment					1480:1488	metformin treatment	1470:1488	metformin treatment of HeLa cells	1470:1502	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	8	51	theme	AMPK	1430:1433	arg1	activation					1435:1444	AMPK activation	1430:1444	AMPK activation	1430:1444	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	8	52	theme	AMPK	1306:1309	arg1	levels					1281:1286	levels	1281:1286	levels of O-GlcNAcylated AMPK	1281:1309	Moreover, 6-diazo-5-oxo-L-norleucine (a glutamine fructose-6-phosphate aminotransferase inhibitor) or thiamet G (an O-GlcNAcase inhibitor) decreased or increased levels of O-GlcNAcylated AMPK, and increased or decreased levels of phosphorylated AMPK, respectively, suggesting that O-GlcNAc modification affects AMPK activation.
31489252	0	53	theme	cell	35:38	arg1	proliferation					40:52	cervical cancer cell proliferation	19:52	cervical cancer cell proliferation	19:52	Metformin inhibits cervical cancer cell proliferation via decreased AMPK O-GlcNAcylation.
31489252	2	54	theme	Antidiabetic	160:171	arg1	drugs					173:177	Antidiabetic drugs	160:177	Antidiabetic drugs	160:177	Antidiabetic drugs are also known to influence cancer progression, as high glucose levels affect both cancer and diabetes.
31489252	0	55	theme	cancer	28:33	arg1	proliferation					40:52	cervical cancer cell proliferation	19:52	cervical cancer cell proliferation	19:52	Metformin inhibits cervical cancer cell proliferation via decreased AMPK O-GlcNAcylation.
31489252	7	56	theme	cell	1033:1036	arg1	arrest					1044:1049	decreased cell cycle arrest	1023:1049	decreased cell cycle arrest	1023:1049	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	6	57	from	interplay	767:775	arg1	cells					829:833	HeLa cells	824:833	HeLa cells	824:833	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	0	58	theme	decreased	58:66	arg1	O-GlcNAcylation					73:87	decreased AMPK O-GlcNAcylation	58:87	decreased AMPK O-GlcNAcylation	58:87	Metformin inhibits cervical cancer cell proliferation via decreased AMPK O-GlcNAcylation.
31489252	6	59	theme	phospho-AMPK	946:957	arg1	levels					936:941	levels	936:941	levels of phospho-AMPK	936:957	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	5	60	theme	cancer	648:653	arg1	cells					655:659	cervical cancer cells	639:659	cervical cancer cells	639:659	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	0	61	theme	AMPK	68:71	arg1	O-GlcNAcylation					73:87	decreased AMPK O-GlcNAcylation	58:87	decreased AMPK O-GlcNAcylation	58:87	Metformin inhibits cervical cancer cell proliferation via decreased AMPK O-GlcNAcylation.
31489252	9	62	theme	cell	1611:1614	arg1	arrest					1622:1627	increased cell cycle arrest	1601:1627	increased cell cycle arrest	1601:1627	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	7	63	theme	cycle	1038:1042	arg1	arrest					1044:1049	decreased cell cycle arrest	1023:1049	decreased cell cycle arrest	1023:1049	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	3	64	theme	cervical	384:391	arg1	system					400:405	cervical cancer system	384:405	cervical cancer system	384:405	Metformin induces cell cycle arrest in cancer cells, but the underlying mechanism remains unclear in cervical cancer system.
31489252	3	65	theme	cell	301:304	arg1	arrest					312:317	cell cycle arrest	301:317	cell cycle arrest	301:317	Metformin induces cell cycle arrest in cancer cells, but the underlying mechanism remains unclear in cervical cancer system.
31489252	2	66	theme	cancer	207:212	arg1	progression					214:224	cancer progression	207:224	cancer progression	207:224	Antidiabetic drugs are also known to influence cancer progression, as high glucose levels affect both cancer and diabetes.
31489252	9	67	theme	AMPK-dependent	1551:1564	arg1	p27					1536:1538	p27	1536:1538	p27	1536:1538	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	67	theme	AMPK-dependent	1551:1564	arg1	p21					1528:1530	p21	1528:1530	p21	1528:1530	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	67	theme	AMPK-dependent	1551:1564	arg1	inhibitors					1577:1586	AMPK-dependent cell cycle inhibitors	1551:1586	AMPK-dependent cell cycle inhibitors	1551:1586	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	10	68	dep	useful	1739:1744	arg1	antiproliferative					1746:1762	antiproliferative	1746:1762	antiproliferative	1746:1762	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	7	69	theme	decreased	1023:1031	arg1	arrest					1044:1049	decreased cell cycle arrest	1023:1049	decreased cell cycle arrest	1023:1049	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	7	70	from	arrest	1044:1049	arg1	cells					1084:1088	HeLa cells	1079:1088	HeLa cells	1079:1088	These results were associated with decreased cell cycle arrest and apoptotic cell death in HeLa cells, as shown by flow cytometry.
31489252	10	71	theme	useful	1739:1744	arg1	drug					1764:1767	a useful antiproliferative drug	1737:1767	a useful antiproliferative drug in cervical cancer cells	1737:1792	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	10	71	theme	useful	1739:1744	arg1	metformin					1714:1722	metformin	1714:1722	metformin	1714:1722	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	6	72	theme	Immunoprecipitation	714:732	arg1	analysis					734:741	Immunoprecipitation analysis	714:741	Immunoprecipitation analysis	714:741	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	9	73	theme	p21	1528:1530	arg1	levels					1518:1523	the levels	1514:1523	the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors)	1514:1587	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	9	74	from	arrest	1622:1627	arg1	cells					1651:1655	HeLa cells	1646:1655	HeLa cells	1646:1655	Of note, we found that metformin treatment of HeLa cells increased the levels of p21 and p27 (which are AMPK-dependent cell cycle inhibitors), leading to increased cell cycle arrest and apoptosis in HeLa cells compared to untreated cells.
31489252	6	75	theme	HeLa	824:827	arg1	cells					829:833	HeLa cells	824:833	HeLa cells	824:833	Immunoprecipitation analysis was used to examine the interplay between O-GlcNAcylation and phosphorylation in HeLa cells, revealing that metformin decreased O-GlcNAcylated AMP-activated protein kinase (AMPK) and increased levels of phospho-AMPK compared to untreated cells.
31489252	2	76	theme	glucose	235:241	arg1	levels					243:248	high glucose levels	230:248	high glucose levels	230:248	Antidiabetic drugs are also known to influence cancer progression, as high glucose levels affect both cancer and diabetes.
31489252	10	77	from	drug	1764:1767	arg1	cells					1788:1792	cervical cancer cells	1772:1792	cervical cancer cells	1772:1792	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	5	78	theme	cervical	639:646	arg1	cells					655:659	cervical cancer cells	639:659	cervical cancer cells	639:659	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	3	79	theme	cancer	322:327	arg1	cells					329:333	cancer cells	322:333	cancer cells	322:333	Metformin induces cell cycle arrest in cancer cells, but the underlying mechanism remains unclear in cervical cancer system.
31489252	10	80	theme	therapeutic	1810:1820	arg1	benefit					1822:1828	potential therapeutic benefit	1800:1828	potential therapeutic benefit	1800:1828	These findings suggest that metformin may serve as a useful antiproliferative drug in cervical cancer cells, with potential therapeutic benefit.
31489252	2	81	theme	high	230:233	arg1	levels					243:248	high glucose levels	230:248	high glucose levels	230:248	Antidiabetic drugs are also known to influence cancer progression, as high glucose levels affect both cancer and diabetes.
31489252	5	82	theme	Western	506:512	arg1	analysis					519:526	Western blot analysis	506:526	Western blot analysis	506:526	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	1	83	theme	type	143:146	arg1	diabetes					150:157	type 2 diabetes	143:157	type 2 diabetes	143:157	Metformin is a widely used drug for the treatment of type 2 diabetes.
31489252	5	84	link	O-linked	550:557	arg1	N-acetylglucosamine					559:577	O-linked N-acetylglucosamine	550:577	O-linked N-acetylglucosamine (O-GlcNAc)	550:588	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31489252	5	84	link	O-linked	550:557	arg1	O-GlcNAc					580:587	O-GlcNAc	580:587	O-GlcNAc	580:587	Western blot analysis showed that levels of O-linked N-acetylglucosamine (O-GlcNAc) and O-GlcNAc transferase (OGT) were increased in cervical cancer cells; these effects were reversed by metformin treatment.
31812980	4	0	theme	factor	808:813	arg1	domains					834:840	epidermal growth factor precursor homology domains	791:840	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	1	theme	transmembrane	843:855	arg1	domains					857:863	transmembrane domains	843:863	transmembrane domains	843:863	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	2	2	theme	ends	345:348	arg1	rapid-amplification					317:335	rapid-amplification	317:335	rapid-amplification of cDNA ends	317:348	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	2	theme	ends	345:348	arg1	reaction					295:302	reverse transcription-polymerase chain reaction	256:302	reverse transcription-polymerase chain reaction (RT-PCR)	256:311	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	2	theme	ends	345:348	arg1	RT-PCR					305:310	RT-PCR	305:310	RT-PCR	305:310	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	0	3	from	Features	10:17	arg1	italicus					83:90	Calliptamus italicus	71:90	Calliptamus italicus (Orthoptera: Acrididae)	71:114	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	4	4	theme	growth	801:806	arg1	factor					808:813	epidermal growth factor	791:813	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	2	5	theme	cDNA	340:343	arg1	ends					345:348	cDNA ends	340:348	cDNA ends	340:348	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	10	6	theme	molecular	1526:1534	arg1	mechanisms					1536:1545	the molecular mechanisms	1522:1545	the molecular mechanisms involved in the reproduction of C. italicus	1522:1589	The findings of this study further our understanding of the molecular mechanisms involved in the reproduction of C. italicus, and provide new ideas to control this insect.
31812980	6	7	theme	Phylogenetic	941:952	arg1	analysis					954:961	Phylogenetic analysis	941:961	Phylogenetic analysis	941:961	Phylogenetic analysis showed that CiVgR had the closest genetic relationship to Blattarias.
31812980	4	8	theme	homology	825:832	arg1	domains					834:840	epidermal growth factor precursor homology domains	791:840	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	2	9	theme	transcription-polymerase	264:287	arg1	reaction					295:302	reverse transcription-polymerase chain reaction	256:302	reverse transcription-polymerase chain reaction (RT-PCR)	256:311	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	9	theme	transcription-polymerase	264:287	arg1	RT-PCR					305:310	RT-PCR	305:310	RT-PCR	305:310	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	8	10	theme	previtellogenesis	1335:1351	arg1	stage					1353:1357	the previtellogenesis stage	1331:1357	the previtellogenesis stage	1331:1357	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	4	11	theme	precursor	815:823	arg1	domains					834:840	epidermal growth factor precursor homology domains	791:840	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	2	12	theme	reverse	256:262	arg1	reaction					295:302	reverse transcription-polymerase chain reaction	256:302	reverse transcription-polymerase chain reaction (RT-PCR)	256:311	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	12	theme	reverse	256:262	arg1	RT-PCR					305:310	RT-PCR	305:310	RT-PCR	305:310	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	8	13	theme	polymerase	1147:1156	arg1	reaction					1164:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	4	14	theme	alignment	606:614	arg1	analysis					616:623	Sequence alignment analysis	597:623	Sequence alignment analysis	597:623	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	8	15	theme	real	1137:1140	arg1	reaction					1164:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	8	16	theme	CiVgR	1206:1210	arg1	transcription					1189:1201	the transcription	1185:1201	the transcription of CiVgR	1185:1210	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	7	17	theme	ovarian	1097:1103	arg1	tissue					1105:1110	the ovarian tissue	1093:1110	the ovarian tissue of females	1093:1121	RT-PCR showed that CiVgR was only specifically expressed in the ovarian tissue of females.
31812980	4	18	theme	ligand-binding	767:780	arg1	domains					782:788	ligand-binding domains	767:788	ligand-binding domains	767:788	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	0	19	dep	Orthoptera	93:102	arg1	Acrididae					105:113	Acrididae	105:113	Acrididae	105:113	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	5	20	link	O-linked	903:910	arg1	domain					918:923	no O-linked sugar domain	900:923	no O-linked sugar domain	900:923	However, no O-linked sugar domain was identified.
31812980	8	21	theme	time	1142:1145	arg1	reaction					1164:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	0	22	from	Patterns	34:41	arg1	italicus					83:90	Calliptamus italicus	71:90	Calliptamus italicus (Orthoptera: Acrididae)	71:114	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	4	23	theme	epidermal	791:799	arg1	factor					808:813	epidermal growth factor	791:813	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	3	24	theme	open	510:513	arg1	frame					523:527	the open reading frame	506:527	the open reading frame	506:527	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	3	24	theme	open	510:513	arg1	bp					555:556	5,265 bp	549:556	5,265 bp	549:556	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	1	25	theme	vitellin	168:175	arg1	intake					158:163	the intake	154:163	the intake of vitellin	154:175	Vitellogenin receptor (VgR) mediates the intake of vitellin via oocytes, thus exerting an important role in vitellogenesis.
31812980	0	26	theme	Molecular	0:8	arg1	Features					10:17	Molecular Features	0:17	Molecular Features	0:17	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	10	27	theme	italicus	1582:1589	arg1	reproduction					1563:1574	the reproduction	1559:1574	the reproduction of C. italicus	1559:1589	The findings of this study further our understanding of the molecular mechanisms involved in the reproduction of C. italicus, and provide new ideas to control this insect.
31812980	0	28	dep	italicus	83:90	arg1	Orthoptera					93:102	Orthoptera	93:102	Orthoptera	93:102	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	9	29	theme	CiVgR	1416:1420	arg1	pattern					1405:1411	The expression pattern	1390:1411	The expression pattern of CiVgR	1390:1420	The expression pattern of CiVgR was closely associated with vitellogenesis.
31812980	0	30	theme	Expression	23:32	arg1	Patterns					34:41	Expression Patterns	23:41	Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae)	23:114	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	8	31	theme	quantitative	1124:1135	arg1	reaction					1164:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	6	32	contain	had	981:983	arg2	relationship					1005:1016	the closest genetic relationship	985:1016	the closest genetic relationship to Blattarias	985:1030	Phylogenetic analysis showed that CiVgR had the closest genetic relationship to Blattarias.
31812980	6	32	contain	had	981:983	arg1	CiVgR					975:979	CiVgR	975:979	CiVgR	975:979	Phylogenetic analysis showed that CiVgR had the closest genetic relationship to Blattarias.
31812980	2	33	theme	reaction	295:302	arg1	techniques					350:359	reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques	256:359	reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques	256:359	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	5	34	theme	O-linked	903:910	arg1	domain					918:923	no O-linked sugar domain	900:923	no O-linked sugar domain	900:923	However, no O-linked sugar domain was identified.
31812980	3	35	theme	reading	515:521	arg1	frame					523:527	the open reading frame	506:527	the open reading frame	506:527	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	3	35	theme	reading	515:521	arg1	bp					555:556	5,265 bp	549:556	5,265 bp	549:556	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	2	36	theme	chain	289:293	arg1	reaction					295:302	reverse transcription-polymerase chain reaction	256:302	reverse transcription-polymerase chain reaction (RT-PCR)	256:311	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	36	theme	chain	289:293	arg1	RT-PCR					305:310	RT-PCR	305:310	RT-PCR	305:310	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	6	37	theme	genetic	997:1003	arg1	relationship					1005:1016	the closest genetic relationship	985:1016	the closest genetic relationship to Blattarias	985:1030	Phylogenetic analysis showed that CiVgR had the closest genetic relationship to Blattarias.
31812980	3	38	theme	full	467:470	arg1	bp					498:499	5,589 bp	492:499	5,589 bp	492:499	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	3	38	theme	full	467:470	arg1	length					472:477	The full length	463:477	The full length of CiVgR	463:486	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	2	39	theme	rapid-amplification	317:335	arg1	techniques					350:359	reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques	256:359	reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques	256:359	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	3	40	theme	amino	579:583	arg1	bp					555:556	5,265 bp	549:556	5,265 bp	549:556	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	3	40	theme	amino	579:583	arg1	aa					592:593	aa	592:593	aa	592:593	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	3	40	theme	amino	579:583	arg1	acids					585:589	1,754 amino acids	573:589	1,754 amino acids (aa)	573:594	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	4	41	dep	lipoprotein	686:696	arg1	genes					707:711	receptor genes	698:711	receptor genes	698:711	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	10	42	theme	new	1604:1606	arg1	ideas					1608:1612	new ideas	1604:1612	new ideas to control this insect	1604:1635	The findings of this study further our understanding of the molecular mechanisms involved in the reproduction of C. italicus, and provide new ideas to control this insect.
31812980	6	43	theme	closest	989:995	arg1	relationship					1005:1016	the closest genetic relationship	985:1016	the closest genetic relationship to Blattarias	985:1030	Phylogenetic analysis showed that CiVgR had the closest genetic relationship to Blattarias.
31812980	9	44	theme	expression	1394:1403	arg1	pattern					1405:1411	The expression pattern	1390:1411	The expression pattern of CiVgR	1390:1420	The expression pattern of CiVgR was closely associated with vitellogenesis.
31812980	4	45	theme	cytoplasmic	870:880	arg1	domains					882:888	cytoplasmic domains	870:888	cytoplasmic domains	870:888	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	46	theme	low-density	674:684	arg1	lipoprotein					686:696	low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains	674:888	lipoprotein	686:696	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	2	47	theme	VgR	410:412	arg1	gene					414:417	the VgR gene	406:417	the VgR gene of Calliptamus italicus	406:441	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	47	theme	VgR	410:412	arg1	gene					393:396	the CiVgR gene	383:396	the CiVgR gene	383:396	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	48	theme	CiVgR	387:391	arg1	gene					414:417	the VgR gene	406:417	the VgR gene of Calliptamus italicus	406:441	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	48	theme	CiVgR	387:391	arg1	gene					393:396	the CiVgR gene	383:396	the CiVgR gene	383:396	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	48	theme	CiVgR	387:391	arg1	Orthopteran					450:460	Orthopteran	450:460	Orthopteran	450:460	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	0	49	theme	Receptor	59:66	arg1	Features					10:17	Molecular Features	0:17	Molecular Features	0:17	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	0	49	theme	Receptor	59:66	arg1	Patterns					34:41	Expression Patterns	23:41	Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae)	23:114	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	5	50	theme	sugar	912:916	arg1	domain					918:923	no O-linked sugar domain	900:923	no O-linked sugar domain	900:923	However, no O-linked sugar domain was identified.
31812980	0	51	theme	Vitellogenin	46:57	arg1	Receptor					59:66	Vitellogenin Receptor	46:66	Vitellogenin Receptor	46:66	Molecular Features and Expression Patterns of Vitellogenin Receptor in Calliptamus italicus (Orthoptera: Acrididae).
31812980	10	52	theme	study	1487:1491	arg1	findings					1470:1477	The findings	1466:1477	The findings of this study	1466:1491	The findings of this study further our understanding of the molecular mechanisms involved in the reproduction of C. italicus, and provide new ideas to control this insect.
31812980	1	53	theme	Vitellogenin	117:128	arg1	receptor					130:137	Vitellogenin receptor	117:137	Vitellogenin receptor (VgR)	117:143	Vitellogenin receptor (VgR) mediates the intake of vitellin via oocytes, thus exerting an important role in vitellogenesis.
31812980	1	53	theme	Vitellogenin	117:128	arg1	VgR					140:142	VgR	140:142	VgR	140:142	Vitellogenin receptor (VgR) mediates the intake of vitellin via oocytes, thus exerting an important role in vitellogenesis.
31812980	7	54	theme	females	1115:1121	arg1	tissue					1105:1110	the ovarian tissue	1093:1110	the ovarian tissue of females	1093:1121	RT-PCR showed that CiVgR was only specifically expressed in the ovarian tissue of females.
31812980	4	55	theme	conserved	738:746	arg1	domains					748:754	several conserved domains	730:754	several conserved domains	730:754	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	55	theme	conserved	738:746	arg1	domains					834:840	epidermal growth factor precursor homology domains	791:840	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	55	theme	conserved	738:746	arg1	domains					857:863	transmembrane domains	843:863	transmembrane domains	843:863	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	55	theme	conserved	738:746	arg1	domains					782:788	ligand-binding domains	767:788	ligand-binding domains	767:788	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	55	theme	conserved	738:746	arg1	domains					882:888	cytoplasmic domains	870:888	cytoplasmic domains	870:888	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	10	56	theme	mechanisms	1536:1545	arg1	understanding					1505:1517	our understanding	1501:1517	our understanding of the molecular mechanisms involved in the reproduction of C. italicus	1501:1589	The findings of this study further our understanding of the molecular mechanisms involved in the reproduction of C. italicus, and provide new ideas to control this insect.
31812980	4	57	contain	contained	720:728	arg2	domains					834:840	epidermal growth factor precursor homology domains	791:840	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	57	contain	contained	720:728	arg2	domains					857:863	transmembrane domains	843:863	transmembrane domains	843:863	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	57	contain	contained	720:728	arg2	domains					882:888	cytoplasmic domains	870:888	cytoplasmic domains	870:888	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	57	contain	contained	720:728	arg2	domains					782:788	ligand-binding domains	767:788	ligand-binding domains	767:788	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	57	contain	contained	720:728	arg2	domains					748:754	several conserved domains	730:754	several conserved domains	730:754	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	57	contain	contained	720:728	arg1	which					714:718	which	714:718	which	714:718	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	58	theme	receptor	698:705	arg1	genes					707:711	receptor genes	698:711	receptor genes	698:711	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	59	theme	lipoprotein	686:696	arg1	superfamily					659:669	the superfamily	655:669	the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains	655:888	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	8	60	theme	italicus	1262:1269	arg1	nymph					1250:1254	the fourth-instar nymph	1232:1254	the fourth-instar nymph	1232:1254	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	8	61	theme	adult	1304:1308	arg1	emergence					1310:1318	adult emergence	1304:1318	adult emergence	1304:1318	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	1	62	theme	important	207:215	arg1	role					217:220	an important role	204:220	an important role	204:220	Vitellogenin receptor (VgR) mediates the intake of vitellin via oocytes, thus exerting an important role in vitellogenesis.
31812980	8	63	theme	fourth-instar	1236:1248	arg1	nymph					1250:1254	the fourth-instar nymph	1232:1254	the fourth-instar nymph	1232:1254	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	4	64	theme	several	730:736	arg1	domains					748:754	several conserved domains	730:754	several conserved domains	730:754	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	64	theme	several	730:736	arg1	domains					834:840	epidermal growth factor precursor homology domains	791:840	epidermal growth factor precursor homology domains	791:840	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	64	theme	several	730:736	arg1	domains					857:863	transmembrane domains	843:863	transmembrane domains	843:863	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	64	theme	several	730:736	arg1	domains					782:788	ligand-binding domains	767:788	ligand-binding domains	767:788	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	64	theme	several	730:736	arg1	domains					882:888	cytoplasmic domains	870:888	cytoplasmic domains	870:888	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	4	65	theme	Sequence	597:604	arg1	analysis					616:623	Sequence alignment analysis	597:623	Sequence alignment analysis	597:623	Sequence alignment analysis showed that CiVgR belonged to the superfamily of low-density lipoprotein receptor genes, which contained several conserved domains, including ligand-binding domains, epidermal growth factor precursor homology domains, transmembrane domains, and cytoplasmic domains.
31812980	2	66	theme	italicus	434:441	arg1	gene					414:417	the VgR gene	406:417	the VgR gene of Calliptamus italicus	406:441	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	2	66	theme	italicus	434:441	arg1	gene					393:396	the CiVgR gene	383:396	the CiVgR gene	383:396	In this study, reverse transcription-polymerase chain reaction (RT-PCR) and rapid-amplification of cDNA ends techniques were adopted to clone the CiVgR gene, namely the VgR gene of Calliptamus italicus, i.e., Orthopteran.
31812980	8	67	theme	chain	1158:1162	arg1	reaction					1164:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction	1124:1171	quantitative real time polymerase chain reaction showed that the transcription of CiVgR already appeared in the fourth-instar nymph of C. italicus, which gradually increased after adult emergence, peaked at the previtellogenesis stage, and then started to decrease.
31812980	3	68	theme	CiVgR	482:486	arg1	bp					498:499	5,589 bp	492:499	5,589 bp	492:499	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31812980	3	68	theme	CiVgR	482:486	arg1	length					472:477	The full length	463:477	The full length of CiVgR	463:486	The full length of CiVgR was 5,589 bp, and the open reading frame was estimated to be 5,265 bp, which encoded 1,754 amino acids (aa).
31704286	0	0	theme	T-cell	68:73	arg1	Responses					75:83	CD8+ T-cell Responses	63:83	CD8+ T-cell Responses	63:83	CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
31704286	1	1	theme	T	141:141	arg1	cells					143:147	T cells	141:147	T cells	141:147	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	0	2	theme	CD8+	63:66	arg1	Responses					75:83	CD8+ T-cell Responses	63:83	CD8+ T-cell Responses	63:83	CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
31704286	0	3	from	Binding	4:10	arg1	trans					47:51	trans	47:51	trans	47:51	CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
31704286	0	3	from	Binding	4:10	arg1	cis					40:42	cis	40:42	cis	40:42	CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
31704286	1	4	theme	cells	143:147	arg1	activation					127:136	activation	127:136	activation of T cells	127:147	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	3	5	theme	charged	782:788	arg1	sequences					790:798	positively charged sequences	771:798	positively charged sequences	771:798	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	6	theme	different	597:605	arg1	mode					615:618	a different docking mode	595:618	a different docking mode	595:618	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	7	theme	energy	464:469	arg1	transfer					471:478	fluorescence resonance energy transfer	441:478	fluorescence resonance energy transfer experiments on living cells	441:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	8	theme	transfer	471:478	arg1	experiments					480:490	fluorescence resonance energy transfer experiments	441:490	fluorescence resonance energy transfer experiments on living cells	441:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	9	from	modeling	431:438	arg1	cells					502:506	living cells	495:506	living cells	495:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	1	10	dep	promote	119:125	arg1	bringing					271:278	bringing	271:278	bringing p56Lck to TCR/CD3	271:296	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	1	10	dep	promote	119:125	arg1	strengthening					152:164	strengthening	152:164	strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells	152:262	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	3	11	from	analysis	536:543	arg1	cells					502:506	living cells	495:506	living cells	495:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	12	from	binding	563:569	arg1	cis					582:584	cis	582:584	cis	582:584	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	5	13	theme	new	1010:1012	arg1	opportunities					1028:1040	new translational opportunities	1010:1040	new translational opportunities	1010:1040	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	3	14	theme	O-linked	749:756	arg1	glycans					758:764	negatively charged O-linked glycans	730:764	negatively charged O-linked glycans near positively charged sequences on the CD8β stalk	730:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	15	theme	fluorescence	441:452	arg1	transfer					471:478	fluorescence resonance energy transfer	441:478	fluorescence resonance energy transfer experiments on living cells	441:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	16	from	bond	721:724	arg1	stalk					812:816	the CD8β stalk	803:816	the CD8β stalk	803:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	17	theme	resonance	454:462	arg1	transfer					471:478	fluorescence resonance energy transfer	441:478	fluorescence resonance energy transfer experiments on living cells	441:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	18	theme	living	495:500	arg1	cells					502:506	living cells	495:506	living cells	495:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	1	19	theme	T-cell	166:171	arg1	TCR					183:185	TCR	183:185	TCR	183:185	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	1	19	theme	T-cell	166:171	arg1	receptor					173:180	T-cell receptor	166:180	T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC)	166:234	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	0	20	theme	CD8	0:2	arg1	Binding					4:10	CD8 Binding	0:10	CD8 Binding of MHC-Peptide Complexes in cis or trans	0:51	CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
31704286	1	21	theme	antigen	239:245	arg1	cells					258:262	antigen presenting cells	239:262	antigen presenting cells	239:262	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	0	22	theme	MHC-Peptide	15:25	arg1	Complexes					27:35	MHC-Peptide Complexes	15:35	MHC-Peptide Complexes	15:35	CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
31704286	1	23	theme	presenting	247:256	arg1	cells					258:262	antigen presenting cells	239:262	antigen presenting cells	239:262	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	3	24	from	glycans	758:764	arg1	stalk					812:816	the CD8β stalk	803:816	the CD8β stalk	803:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	25	link	O-linked	749:756	arg1	glycans					758:764	negatively charged O-linked glycans	730:764	negatively charged O-linked glycans near positively charged sequences on the CD8β stalk	730:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	2	26	theme	T	358:358	arg1	cell					360:363	the T cell	354:363	the T cell	354:363	Here, we demonstrate that CD8 can also bind to pMHC on the T cell (in cis) and that this inhibits their activation.
31704286	3	27	theme	posttranslational	640:656	arg1	modifications					658:670	posttranslational modifications	640:670	posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk	640:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	27	theme	posttranslational	640:656	arg1	glycans					758:764	negatively charged O-linked glycans	730:764	negatively charged O-linked glycans near positively charged sequences on the CD8β stalk	730:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	27	theme	posttranslational	640:656	arg1	bond					721:724	a membrane-distal interchain disulfide bond	682:724	a membrane-distal interchain disulfide bond	682:724	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	5	28	theme	CD8+	975:978	arg1	responses					987:995	CD8+ T-cell responses	975:995	CD8+ T-cell responses	975:995	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	1	29	theme	coreceptor	90:99	arg1	CD8αβ					101:105	The coreceptor CD8αβ	86:105	The coreceptor CD8αβ	86:105	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	5	30	theme	T-cell	980:985	arg1	responses					987:995	CD8+ T-cell responses	975:995	CD8+ T-cell responses	975:995	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	0	31	theme	Complexes	27:35	arg1	Binding					4:10	CD8 Binding	0:10	CD8 Binding of MHC-Peptide Complexes in cis or trans	0:51	CD8 Binding of MHC-Peptide Complexes in cis or trans Regulates CD8+ T-cell Responses.
31704286	3	32	theme	disulfide	711:719	arg1	bond					721:724	a membrane-distal interchain disulfide bond	682:724	a membrane-distal interchain disulfide bond	682:724	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	4	33	theme	CD8	872:874	arg1	binding					876:882	CD8 binding	872:882	CD8 binding to pMHC	872:890	These modifications distort the stalk, thus favoring CD8 binding to pMHC in cis.
31704286	3	34	theme	mutational	525:534	arg1	analysis					536:543	mutational analysis	525:543	mutational analysis	525:543	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	35	theme	CD8	559:561	arg1	binding					563:569	CD8 binding	559:569	CD8 binding to pMHC in cis	559:584	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	5	36	theme	Differential	900:911	arg1	binding					913:919	Differential binding	900:919	Differential binding of CD8 to pMHC in cis or trans	900:950	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	5	36	theme	Differential	900:911	arg1	means					957:961	a means	955:961	a means to regulate CD8+ T-cell responses	955:995	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	5	37	theme	translational	1014:1026	arg1	opportunities					1028:1040	new translational opportunities	1010:1040	new translational opportunities	1010:1040	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	3	38	theme	membrane-distal	684:698	arg1	bond					721:724	a membrane-distal interchain disulfide bond	682:724	a membrane-distal interchain disulfide bond	682:724	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	39	theme	molecular	421:429	arg1	modeling					431:438	molecular modeling	421:438	molecular modeling	421:438	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	40	from	experiments	480:490	arg1	cells					502:506	living cells	495:506	living cells	495:506	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	41	theme	interchain	700:709	arg1	bond					721:724	a membrane-distal interchain disulfide bond	682:724	a membrane-distal interchain disulfide bond	682:724	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	5	42	theme	CD8	924:926	arg1	binding					913:919	Differential binding	900:919	Differential binding of CD8 to pMHC in cis or trans	900:950	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	5	42	theme	CD8	924:926	arg1	means					957:961	a means	955:961	a means to regulate CD8+ T-cell responses	955:995	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	3	43	theme	CD8β	807:810	arg1	stalk					812:816	the CD8β stalk	803:816	the CD8β stalk	803:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	3	44	theme	charged	741:747	arg1	glycans					758:764	negatively charged O-linked glycans	730:764	negatively charged O-linked glycans near positively charged sequences on the CD8β stalk	730:816	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	1	45	theme	cognate	199:205	arg1	pMHC					230:233	pMHC	230:233	pMHC	230:233	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	1	45	theme	cognate	199:205	arg1	complexes					219:227	cognate peptide-MHC complexes	199:227	cognate peptide-MHC complexes (pMHC)	199:234	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	5	46	from	pMHC	931:934	arg1	trans					946:950	trans	946:950	trans	946:950	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	5	46	from	pMHC	931:934	arg1	cis					939:941	cis	939:941	cis	939:941	Differential binding of CD8 to pMHC in cis or trans is a means to regulate CD8+ T-cell responses and provides new translational opportunities.
31704286	1	47	theme	peptide-MHC	207:217	arg1	pMHC					230:233	pMHC	230:233	pMHC	230:233	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	1	47	theme	peptide-MHC	207:217	arg1	complexes					219:227	cognate peptide-MHC complexes	199:227	cognate peptide-MHC complexes (pMHC)	199:234	The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3.
31704286	3	48	theme	docking	607:613	arg1	mode					615:618	a different docking mode	595:618	a different docking mode	595:618	Using molecular modeling, fluorescence resonance energy transfer experiments on living cells, biochemical and mutational analysis, we show that CD8 binding to pMHC in cis involves a different docking mode and is regulated by posttranslational modifications including a membrane-distal interchain disulfide bond and negatively charged O-linked glycans near positively charged sequences on the CD8β stalk.
31704286	2	49	dep	bind	338:341	arg1	cis					369:371	cis	369:371	cis	369:371	Here, we demonstrate that CD8 can also bind to pMHC on the T cell (in cis) and that this inhibits their activation.
31237748	1	0	link	O-linked	87:94	arg1	N-acetylglucosamine					96:114	Protein O-linked N-acetylglucosamine	79:114	Protein O-linked N-acetylglucosamine (O-GlcNAc)	79:125	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	0	link	O-linked	87:94	arg1	modification					151:162	a post-translational modification	130:162	a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors	130:297	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	0	link	O-linked	87:94	arg1	O-GlcNAc					117:124	O-GlcNAc	117:124	O-GlcNAc	117:124	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	9	1	theme	significant	1377:1387	arg1	effect					1389:1394	a significant effect	1375:1394	a significant effect	1375:1394	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	1	2	theme	intracellular	167:179	arg1	response					269:276	response	269:276	response to various stressors	269:297	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	2	theme	intracellular	167:179	arg1	proteins					181:188	intracellular proteins	167:188	intracellular proteins	167:188	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	4	3	theme	compression	775:785	arg1	forces					787:792	0, 1.5, 3, 7 and 14 g/cm2 compression forces	749:792	0, 1.5, 3, 7 and 14 g/cm2 compression forces	749:792	In this study, PDL cells isolated from premolars extracted for orthodontic indications were exposed to 0, 1.5, 3, 7 and 14 g/cm2 compression forces for 12 hours.
31237748	1	4	theme	proteins	181:188	arg1	N-acetylglucosamine					96:114	Protein O-linked N-acetylglucosamine	79:114	Protein O-linked N-acetylglucosamine (O-GlcNAc)	79:125	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	4	theme	proteins	181:188	arg1	modification					151:162	a post-translational modification	130:162	a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors	130:297	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	3	5	theme	periodontal	390:400	arg1	PDL					412:414	PDL	412:414	PDL	412:414	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	3	5	theme	periodontal	390:400	arg1	ligament					402:409	human periodontal ligament	384:409	human periodontal ligament (PDL) cells	384:421	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	6	6	theme	Cellular	906:913	arg1	structure					915:923	Cellular structure	906:923	Cellular structure	906:923	Cellular structure and intracellular distribution of O-GlcNAc was studied by immunofluorescence microscopy.
31237748	7	7	theme	O-GlcNAc	1135:1142	arg1	level					1144:1148	higher forces O-GlcNAc level	1121:1148	higher forces O-GlcNAc level	1121:1148	We found that between 1.5 and 3 g/cm2 mechanical compression, O-GlcNAc significantly elevated; however, at higher forces O-GlcNAc level was not increased.
31237748	5	8	theme	Western	892:898	arg1	blot					900:903	Western blot	892:903	Western blot	892:903	Cell viability was measured by flow cytometry, and protein O-GlcNAc was analysed by Western blot.
31237748	9	9	theme	compression	1351:1361	arg1	forces					1363:1368	compression forces	1351:1368	compression forces	1351:1368	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	3	10	theme	ligament	402:409	arg1	cells					417:421	human periodontal ligament (PDL) cells	384:421	human periodontal ligament (PDL) cells	384:421	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	9	11	theme	O-GlcNAc	1417:1424	arg1	regulation					1403:1412	the regulation	1399:1412	the regulation of O-GlcNAc	1399:1424	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	9	12	theme	PDL	1493:1495	arg1	cells					1497:1501	PDL cells	1493:1501	PDL cells	1493:1501	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	5	13	theme	protein	859:865	arg1	O-GlcNAc					867:874	protein O-GlcNAc	859:874	protein O-GlcNAc	859:874	Cell viability was measured by flow cytometry, and protein O-GlcNAc was analysed by Western blot.
31237748	7	14	theme	higher	1121:1126	arg1	level					1144:1148	higher forces O-GlcNAc level	1121:1148	higher forces O-GlcNAc level	1121:1148	We found that between 1.5 and 3 g/cm2 mechanical compression, O-GlcNAc significantly elevated; however, at higher forces O-GlcNAc level was not increased.
31237748	9	15	theme	cells	1497:1501	arg1	adaptation					1479:1488	the mechanical stress adaptation	1457:1488	the mechanical stress adaptation of PDL cells	1457:1501	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	3	16	theme	orthodontic	466:476	arg1	movement					484:491	orthodontic tooth movement	466:491	orthodontic tooth movement that results in structural remodelling	466:530	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	3	17	theme	human	384:388	arg1	PDL					412:414	PDL	412:414	PDL	412:414	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	3	17	theme	human	384:388	arg1	ligament					402:409	human periodontal ligament	384:409	human periodontal ligament (PDL) cells	384:421	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	7	18	theme	forces	1128:1133	arg1	level					1144:1148	higher forces O-GlcNAc level	1121:1148	higher forces O-GlcNAc level	1121:1148	We found that between 1.5 and 3 g/cm2 mechanical compression, O-GlcNAc significantly elevated; however, at higher forces O-GlcNAc level was not increased.
31237748	1	19	theme	Protein	79:85	arg1	N-acetylglucosamine					96:114	Protein O-linked N-acetylglucosamine	79:114	Protein O-linked N-acetylglucosamine (O-GlcNAc)	79:125	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	19	theme	Protein	79:85	arg1	modification					151:162	a post-translational modification	130:162	a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors	130:297	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	19	theme	Protein	79:85	arg1	O-GlcNAc					117:124	O-GlcNAc	117:124	O-GlcNAc	117:124	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	3	20	theme	tooth	478:482	arg1	movement					484:491	orthodontic tooth movement	466:491	orthodontic tooth movement that results in structural remodelling	466:530	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	8	21	theme	O-GlcNAc	1218:1225	arg1	proteins					1227:1234	O-GlcNAc proteins	1218:1234	O-GlcNAc proteins	1218:1234	We also found that intracellular localization of O-GlcNAc proteins became more centralized under 2 g/cm2 compression force.
31237748	0	22	from	O-GlcNAc	33:40	arg1	cells					72:76	human periodontal ligament cells	45:76	human periodontal ligament cells	45:76	Mechanical stress alters protein O-GlcNAc in human periodontal ligament cells.
31237748	1	23	theme	O-linked	87:94	arg1	N-acetylglucosamine					96:114	Protein O-linked N-acetylglucosamine	79:114	Protein O-linked N-acetylglucosamine (O-GlcNAc)	79:125	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	23	theme	O-linked	87:94	arg1	modification					151:162	a post-translational modification	130:162	a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors	130:297	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	23	theme	O-linked	87:94	arg1	O-GlcNAc					117:124	O-GlcNAc	117:124	O-GlcNAc	117:124	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	24	theme	several	205:211	arg1	process					250:256	several physiological and pathophysiological process	205:256	several physiological and pathophysiological process	205:256	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	0	25	theme	Mechanical	0:9	arg1	stress					11:16	Mechanical stress	0:16	Mechanical stress	0:16	Mechanical stress alters protein O-GlcNAc in human periodontal ligament cells.
31237748	9	26	theme	structural	1318:1327	arg1	changes					1329:1335	structural changes	1318:1335	structural changes stimulated by compression forces	1318:1368	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	3	27	theme	protein	615:621	arg1	O-GlcNAc					623:630	protein O-GlcNAc	615:630	protein O-GlcNAc in PDL cells	615:643	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	3	28	from	O-GlcNAc	623:630	arg1	cells					639:643	PDL cells	635:643	PDL cells	635:643	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	1	29	theme	physiological	213:225	arg1	process					250:256	several physiological and pathophysiological process	205:256	several physiological and pathophysiological process	205:256	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	0	30	theme	protein	25:31	arg1	O-GlcNAc					33:40	protein O-GlcNAc	25:40	protein O-GlcNAc in human periodontal ligament cells	25:76	Mechanical stress alters protein O-GlcNAc in human periodontal ligament cells.
31237748	6	31	theme	immunofluorescence	983:1000	arg1	microscopy					1002:1011	immunofluorescence microscopy	983:1011	immunofluorescence microscopy	983:1011	Cellular structure and intracellular distribution of O-GlcNAc was studied by immunofluorescence microscopy.
31237748	9	32	theme	mechanical	1461:1470	arg1	adaptation					1479:1488	the mechanical stress adaptation	1457:1488	the mechanical stress adaptation of PDL cells	1457:1501	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	4	33	theme	PDL	661:663	arg1	cells					665:669	PDL cells	661:669	PDL cells isolated from premolars extracted for orthodontic indications	661:731	In this study, PDL cells isolated from premolars extracted for orthodontic indications were exposed to 0, 1.5, 3, 7 and 14 g/cm2 compression forces for 12 hours.
31237748	8	34	theme	proteins	1227:1234	arg1	localization					1202:1213	intracellular localization	1188:1213	intracellular localization of O-GlcNAc proteins	1188:1234	We also found that intracellular localization of O-GlcNAc proteins became more centralized under 2 g/cm2 compression force.
31237748	2	35	theme	mechanical	332:341	arg1	stress					343:348	mechanical stress	332:348	mechanical stress	332:348	However, O-GlcNAc's response to mechanical stress has not been investigated yet.
31237748	9	36	contain	have	1370:1373	arg2	effect					1389:1394	a significant effect	1375:1394	a significant effect	1375:1394	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	9	36	contain	have	1370:1373	arg1	changes					1329:1335	structural changes	1318:1335	structural changes stimulated by compression forces	1318:1368	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	1	37	theme	pathophysiological	231:248	arg1	process					250:256	several physiological and pathophysiological process	205:256	several physiological and pathophysiological process	205:256	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	3	38	theme	PDL	635:637	arg1	cells					639:643	PDL cells	635:643	PDL cells	635:643	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	3	39	theme	compression	441:451	arg1	force					453:457	compression force	441:457	compression force	441:457	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	8	40	theme	intracellular	1188:1200	arg1	localization					1202:1213	intracellular localization	1188:1213	intracellular localization of O-GlcNAc proteins	1188:1234	We also found that intracellular localization of O-GlcNAc proteins became more centralized under 2 g/cm2 compression force.
31237748	0	41	theme	periodontal	51:61	arg1	cells					72:76	human periodontal ligament cells	45:76	human periodontal ligament cells	45:76	Mechanical stress alters protein O-GlcNAc in human periodontal ligament cells.
31237748	6	42	theme	O-GlcNAc	959:966	arg1	structure					915:923	Cellular structure	906:923	Cellular structure	906:923	Cellular structure and intracellular distribution of O-GlcNAc was studied by immunofluorescence microscopy.
31237748	6	42	theme	O-GlcNAc	959:966	arg1	distribution					943:954	intracellular distribution	929:954	intracellular distribution	929:954	Cellular structure and intracellular distribution of O-GlcNAc was studied by immunofluorescence microscopy.
31237748	5	43	theme	Cell	808:811	arg1	viability					813:821	Cell viability	808:821	Cell viability	808:821	Cell viability was measured by flow cytometry, and protein O-GlcNAc was analysed by Western blot.
31237748	7	44	theme	3 g/cm2	1044:1050	arg1	compression					1063:1073	3 g/cm2 mechanical compression	1044:1073	3 g/cm2 mechanical compression	1044:1073	We found that between 1.5 and 3 g/cm2 mechanical compression, O-GlcNAc significantly elevated; however, at higher forces O-GlcNAc level was not increased.
31237748	0	45	theme	human	45:49	arg1	cells					72:76	human periodontal ligament cells	45:76	human periodontal ligament cells	45:76	Mechanical stress alters protein O-GlcNAc in human periodontal ligament cells.
31237748	7	46	theme	mechanical	1052:1061	arg1	compression					1063:1073	3 g/cm2 mechanical compression	1044:1073	3 g/cm2 mechanical compression	1044:1073	We found that between 1.5 and 3 g/cm2 mechanical compression, O-GlcNAc significantly elevated; however, at higher forces O-GlcNAc level was not increased.
31237748	3	47	theme	structural	509:518	arg1	remodelling					520:530	structural remodelling	509:530	structural remodelling	509:530	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	9	48	theme	stress	1472:1477	arg1	adaptation					1479:1488	the mechanical stress adaptation	1457:1488	the mechanical stress adaptation of PDL cells	1457:1501	Our results suggest that structural changes stimulated by compression forces have a significant effect on the regulation of O-GlcNAc; thus, it might play a role in the mechanical stress adaptation of PDL cells.
31237748	3	49	theme	mechanical	571:580	arg1	stress					582:587	mechanical stress	571:587	mechanical stress	571:587	As human periodontal ligament (PDL) cells are stimulated by compression force during orthodontic tooth movement that results in structural remodelling, in this study we investigated whether mechanical stress induces any alteration in protein O-GlcNAc in PDL cells.
31237748	1	50	theme	post-translational	132:149	arg1	N-acetylglucosamine					96:114	Protein O-linked N-acetylglucosamine	79:114	Protein O-linked N-acetylglucosamine (O-GlcNAc)	79:125	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	1	50	theme	post-translational	132:149	arg1	modification					151:162	a post-translational modification	130:162	a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors	130:297	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
31237748	8	51	theme	2 g/cm2	1266:1272	arg1	force					1286:1290	2 g/cm2 compression force	1266:1290	2 g/cm2 compression force	1266:1290	We also found that intracellular localization of O-GlcNAc proteins became more centralized under 2 g/cm2 compression force.
31237748	4	52	attach	isolated	671:678	arg1	premolars					685:693	premolars	685:693	premolars extracted for orthodontic indications	685:731	In this study, PDL cells isolated from premolars extracted for orthodontic indications were exposed to 0, 1.5, 3, 7 and 14 g/cm2 compression forces for 12 hours.
31237748	4	52	attach	isolated	671:678	arg2	cells					665:669	PDL cells	661:669	PDL cells isolated from premolars extracted for orthodontic indications	661:731	In this study, PDL cells isolated from premolars extracted for orthodontic indications were exposed to 0, 1.5, 3, 7 and 14 g/cm2 compression forces for 12 hours.
31237748	5	53	theme	flow	839:842	arg1	cytometry					844:852	flow cytometry	839:852	flow cytometry	839:852	Cell viability was measured by flow cytometry, and protein O-GlcNAc was analysed by Western blot.
31237748	8	54	theme	compression	1274:1284	arg1	force					1286:1290	2 g/cm2 compression force	1266:1290	2 g/cm2 compression force	1266:1290	We also found that intracellular localization of O-GlcNAc proteins became more centralized under 2 g/cm2 compression force.
31237748	0	55	theme	ligament	63:70	arg1	cells					72:76	human periodontal ligament cells	45:76	human periodontal ligament cells	45:76	Mechanical stress alters protein O-GlcNAc in human periodontal ligament cells.
31237748	6	56	theme	intracellular	929:941	arg1	distribution					943:954	intracellular distribution	929:954	intracellular distribution	929:954	Cellular structure and intracellular distribution of O-GlcNAc was studied by immunofluorescence microscopy.
31237748	4	57	theme	orthodontic	709:719	arg1	indications					721:731	orthodontic indications	709:731	orthodontic indications	709:731	In this study, PDL cells isolated from premolars extracted for orthodontic indications were exposed to 0, 1.5, 3, 7 and 14 g/cm2 compression forces for 12 hours.
31237748	1	58	theme	various	281:287	arg1	stressors					289:297	various stressors	281:297	various stressors	281:297	Protein O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of intracellular proteins that regulates several physiological and pathophysiological process, including response to various stressors.
33405649	0	0	theme	Lipopolymer	104:114	arg1	Nanoparticles					116:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Protection against Neurodegeneration in the Hippocampus Using Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles.
33405649	0	1	from	Neurodegeneration	19:35	arg1	Hippocampus					44:54	the Hippocampus	40:54	the Hippocampus	40:54	Protection against Neurodegeneration in the Hippocampus Using Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles.
33405649	7	2	from	formation	1412:1420	arg1	hippocampus					1498:1508	the hippocampus	1494:1508	the hippocampus	1494:1508	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	4	3	theme	O-linked	1035:1042	arg1	N-acetylglucosamine					1044:1062	O-linked N-acetylglucosamine	1035:1062	O-linked N-acetylglucosamine	1035:1062	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	4	4	theme	SA	1018:1019	arg1	interactions					994:1005	strong interactions	987:1005	strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors	987:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	5	5	theme	AD	1205:1206	arg1	brain					1212:1216	AD rat brain	1205:1216	AD rat brain	1205:1216	Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain.
33405649	0	6	theme	5-HT-Moduline-Conjugated	79:102	arg1	Nanoparticles					116:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Protection against Neurodegeneration in the Hippocampus Using Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles.
33405649	1	7	theme	neurodegenerative	342:358	arg1	disease					360:366	this neurodegenerative disease	337:366	this neurodegenerative disease	337:366	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	2	8	dep	nanoparticles	448:460	arg1	incorporated					468:479	incorporated	468:479	incorporated with phosphatidic acid (PA)	468:507	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	2	8	dep	nanoparticles	448:460	arg1	modified					513:520	modified	513:520	modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM)	513:582	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	8	9	theme	NPs	1555:1557	arg1	medication					1522:1531	the medication	1518:1531	the medication of QU-SA-5HTM-PA-PLGA NPs	1518:1557	Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.
33405649	1	10	theme	clinical	253:260	arg1	trials					262:267	clinical trials	253:267	clinical trials	253:267	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	4	11	theme	lipopolymeric	889:901	arg1	NPs					903:905	the lipopolymeric NPs	885:905	the lipopolymeric NPs	885:905	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	5	12	theme	Immunofluorescence	1100:1117	arg1	images					1128:1133	Immunofluorescence staining images	1100:1133	Immunofluorescence staining images	1100:1133	Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain.
33405649	4	13	link	O-linked	1035:1042	arg1	N-acetylglucosamine					1044:1062	O-linked N-acetylglucosamine	1035:1062	O-linked N-acetylglucosamine	1035:1062	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	7	14	theme	malondialdehyde	1466:1480	arg1	activity					1482:1489	the attenuated acetylcholinesterase and malondialdehyde activity	1426:1489	activity	1482:1489	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	4	15	theme	5HTM	1025:1028	arg1	interactions					994:1005	strong interactions	987:1005	strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors	987:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	1	16	theme	trials	262:267	arg1	number					243:248	a great number	235:248	a great number of clinical trials	235:267	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	3	17	theme	Morphological	680:692	arg1	studies					694:700	Morphological studies	680:700	Morphological studies	680:700	Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation.
33405649	4	18	with	interactions	994:1005	arg1	receptors					1075:1083	O-linked N-acetylglucosamine and 5-HT1B receptors	1035:1083	O-linked N-acetylglucosamine and 5-HT1B receptors	1035:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	3	19	theme	NPs	752:754	arg1	exterior					721:728	a uniform exterior	711:728	a uniform exterior of QU-SA-5HTM-PA-PLGA NPs	711:754	Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation.
33405649	2	20	theme	QU	606:607	arg1	activity					610:617	quercetin (QU) activity	595:617	quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits	595:677	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	4	21	theme	QU	976:977	arg1	permeability					960:971	the high blood-brain barrier (BBB) permeability	925:971	the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors	925:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	2	22	theme	quercetin	595:603	arg1	activity					610:617	quercetin (QU) activity	595:617	quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits	595:677	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	4	23	theme	strong	987:992	arg1	interactions					994:1005	strong interactions	987:1005	strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors	987:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	2	24	theme	lipopolymer	392:402	arg1	system					404:409	a lipopolymer system	390:409	a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM)	390:582	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	8	25	theme	lipid	1623:1627	arg1	peroxidation					1629:1640	lipid peroxidation	1623:1640	lipid peroxidation	1623:1640	Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.
33405649	6	26	theme	QU-loaded	1253:1261	arg1	NPs					1271:1273	QU-loaded PA-PLGA NPs	1253:1273	QU-loaded PA-PLGA NPs	1253:1273	Western blot analysis showed that QU-loaded PA-PLGA NPs suppressed caspase-3 expression.
33405649	7	27	theme	nanocarriers	1327:1338	arg1	ability					1312:1318	The ability	1308:1318	The ability of the nanocarriers to recognize Aβ fibrils	1308:1362	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	2	28	theme	PLGA	442:445	arg1	NPs					463:465	NPs	463:465	NPs	463:465	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	2	28	theme	PLGA	442:445	arg1	nanoparticles					448:460	poly(lactide-co-glycolide) (PLGA) nanoparticles	414:460	poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM)	414:582	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	3	29	theme	uniform	713:719	arg1	exterior					721:728	a uniform exterior	711:728	a uniform exterior of QU-SA-5HTM-PA-PLGA NPs	711:754	Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation.
33405649	7	30	theme	attenuated	1430:1439	arg1	acetylcholinesterase					1441:1460	the attenuated acetylcholinesterase and malondialdehyde activity	1426:1489	acetylcholinesterase	1441:1460	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	8	31	theme	AD	1674:1675	arg1	management					1677:1686	the AD management	1670:1686	the AD management	1670:1686	Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.
33405649	4	32	theme	surface	1010:1016	arg1	SA					1018:1019	surface SA	1010:1019	surface SA	1010:1019	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	1	33	theme	limited	282:288	arg1	success					290:296	the limited success	278:296	the limited success of antioxidant therapy in dealing with this neurodegenerative disease	278:366	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	4	34	theme	NPs	903:905	arg1	delivery					873:880	A better brain-targeted delivery	849:880	A better brain-targeted delivery of the lipopolymeric NPs	849:905	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	2	35	theme	oxidative	627:635	arg1	stress					637:642	oxidative stress	627:642	oxidative stress induced by amyloid-β (Aβ) deposits	627:677	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	1	36	theme	Significant	131:141	arg1	involvement					143:153	Significant involvement	131:153	Significant involvement of oxidative stress in the brain	131:186	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	8	37	theme	QU-SA-5HTM-PA-PLGA	1536:1553	arg1	NPs					1555:1557	QU-SA-5HTM-PA-PLGA NPs	1536:1557	QU-SA-5HTM-PA-PLGA NPs	1536:1557	Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.
33405649	2	38	theme	lactide-co-glycolide	419:438	arg1	NPs					463:465	NPs	463:465	NPs	463:465	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	2	38	theme	lactide-co-glycolide	419:438	arg1	nanoparticles					448:460	poly(lactide-co-glycolide) (PLGA) nanoparticles	414:460	poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM)	414:582	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	5	39	theme	staining	1119:1126	arg1	images					1128:1133	Immunofluorescence staining images	1100:1133	Immunofluorescence staining images	1100:1133	Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain.
33405649	2	40	theme	sialic	527:532	arg1	SA					540:541	SA	540:541	SA	540:541	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	2	40	theme	sialic	527:532	arg1	acid					534:537	sialic acid	527:537	sialic acid (SA)	527:542	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	8	41	theme	BBB	1578:1580	arg1	penetration					1582:1592	the BBB penetration	1574:1592	the BBB penetration	1574:1592	Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.
33405649	8	42	theme	Aβ	1606:1607	arg1	accumulation					1609:1620	Aβ accumulation	1606:1620	Aβ accumulation	1606:1620	Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.
33405649	7	43	theme	senile	1398:1403	arg1	formation					1412:1420	reduced senile plaque formation	1390:1420	reduced senile plaque formation	1390:1420	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	2	44	theme	poly	414:417	arg1	NPs					463:465	NPs	463:465	NPs	463:465	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	2	44	theme	poly	414:417	arg1	nanoparticles					448:460	poly(lactide-co-glycolide) (PLGA) nanoparticles	414:460	poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM)	414:582	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	6	45	theme	PA-PLGA	1263:1269	arg1	NPs					1271:1273	QU-loaded PA-PLGA NPs	1253:1273	QU-loaded PA-PLGA NPs	1253:1273	Western blot analysis showed that QU-loaded PA-PLGA NPs suppressed caspase-3 expression.
33405649	1	46	theme	antioxidant	301:311	arg1	therapy					313:319	antioxidant therapy	301:319	antioxidant therapy	301:319	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	3	47	from	inclusion	813:821	arg1	formulation					836:846	the formulation	832:846	the formulation	832:846	Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation.
33405649	5	48	theme	rat	1208:1210	arg1	brain					1212:1216	AD rat brain	1205:1216	AD rat brain	1205:1216	Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain.
33405649	7	49	theme	plaque	1405:1410	arg1	formation					1412:1420	reduced senile plaque formation	1390:1420	reduced senile plaque formation	1390:1420	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	7	50	theme	reduced	1390:1396	arg1	formation					1412:1420	reduced senile plaque formation	1390:1420	reduced senile plaque formation	1390:1420	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	4	51	theme	high	929:932	arg1	BBB					955:957	BBB	955:957	BBB	955:957	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	4	51	theme	high	929:932	arg1	barrier					946:952	the high blood-brain barrier	925:952	the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors	925:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	0	52	theme	Sialic	62:67	arg1	Nanoparticles					116:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Protection against Neurodegeneration in the Hippocampus Using Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles.
33405649	1	53	theme	therapy	313:319	arg1	success					290:296	the limited success	278:296	the limited success of antioxidant therapy in dealing with this neurodegenerative disease	278:366	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	4	54	theme	better	851:856	arg1	delivery					873:880	A better brain-targeted delivery	849:880	A better brain-targeted delivery of the lipopolymeric NPs	849:905	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	2	55	theme	phosphatidic	486:497	arg1	PA					505:506	PA	505:506	PA	505:506	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	2	55	theme	phosphatidic	486:497	arg1	acid					499:502	phosphatidic acid	486:502	phosphatidic acid (PA)	486:507	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	6	56	theme	blot	1227:1230	arg1	analysis					1232:1239	Western blot analysis	1219:1239	Western blot analysis	1219:1239	Western blot analysis showed that QU-loaded PA-PLGA NPs suppressed caspase-3 expression.
33405649	2	57	theme	nanoparticles	448:460	arg1	system					404:409	a lipopolymer system	390:409	a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM)	390:582	Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-β (Aβ) deposits.
33405649	4	58	theme	brain-targeted	858:871	arg1	delivery					873:880	A better brain-targeted delivery	849:880	A better brain-targeted delivery of the lipopolymeric NPs	849:905	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	4	59	theme	barrier	946:952	arg1	permeability					960:971	the high blood-brain barrier (BBB) permeability	925:971	the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors	925:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	7	60	theme	Aβ	1353:1354	arg1	fibrils					1356:1362	Aβ fibrils	1353:1362	Aβ fibrils	1353:1362	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	1	61	theme	oxidative	158:166	arg1	stress					168:173	oxidative stress	158:173	oxidative stress	158:173	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	4	62	theme	N-acetylglucosamine	1044:1062	arg1	receptors					1075:1083	O-linked N-acetylglucosamine and 5-HT1B receptors	1035:1083	O-linked N-acetylglucosamine and 5-HT1B receptors	1035:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	3	63	theme	QU-SA-5HTM-PA-PLGA	733:750	arg1	NPs					752:754	QU-SA-5HTM-PA-PLGA NPs	733:754	QU-SA-5HTM-PA-PLGA NPs	733:754	Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation.
33405649	5	64	theme	brain	1212:1216	arg1	microvessels					1189:1200	the microvessels	1185:1200	the microvessels of AD rat brain	1185:1216	Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain.
33405649	1	65	theme	stress	168:173	arg1	involvement					143:153	Significant involvement	131:153	Significant involvement of oxidative stress in the brain	131:186	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	1	66	from	involvement	143:153	arg1	brain					182:186	the brain	178:186	the brain	178:186	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	8	67	theme	neuronal	1647:1654	arg1	apoptosis					1656:1664	neuronal apoptosis	1647:1664	neuronal apoptosis	1647:1664	Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent Aβ accumulation, lipid peroxidation, and neuronal apoptosis for the AD management.
33405649	4	68	theme	5-HT1B	1068:1073	arg1	receptors					1075:1083	O-linked N-acetylglucosamine and 5-HT1B receptors	1035:1083	O-linked N-acetylglucosamine and 5-HT1B receptors	1035:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	7	69	from	activity	1482:1489	arg1	hippocampus					1498:1508	the hippocampus	1494:1508	the hippocampus	1494:1508	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	4	70	theme	blood-brain	934:944	arg1	BBB					955:957	BBB	955:957	BBB	955:957	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	4	70	theme	blood-brain	934:944	arg1	barrier					946:952	the high blood-brain barrier	925:952	the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors	925:1083	A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively.
33405649	7	71	from	acetylcholinesterase	1441:1460	arg1	hippocampus					1498:1508	the hippocampus	1494:1508	the hippocampus	1494:1508	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	7	72	dep	formation	1412:1420	arg1	the					1386:1388	the	1386:1388	the	1386:1388	The ability of the nanocarriers to recognize Aβ fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus.
33405649	3	73	theme	PA	826:827	arg1	inclusion					813:821	inclusion	813:821	inclusion of PA in the formulation	813:846	Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation.
33405649	1	74	theme	great	237:241	arg1	number					243:248	a great number	235:248	a great number of clinical trials	235:267	Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease.
33405649	0	75	theme	Acid-	69:73	arg1	Nanoparticles					116:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles	62:128	Protection against Neurodegeneration in the Hippocampus Using Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles.
33405649	5	76	theme	QU-SA-5HTM-PA-PLGA	1150:1167	arg1	NPs					1169:1171	QU-SA-5HTM-PA-PLGA NPs	1150:1171	QU-SA-5HTM-PA-PLGA NPs	1150:1171	Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain.
33405649	6	77	theme	Western	1219:1225	arg1	analysis					1232:1239	Western blot analysis	1219:1239	Western blot analysis	1219:1239	Western blot analysis showed that QU-loaded PA-PLGA NPs suppressed caspase-3 expression.
33405649	6	78	theme	caspase-3	1286:1294	arg1	expression					1296:1305	caspase-3 expression	1286:1305	caspase-3 expression	1286:1305	Western blot analysis showed that QU-loaded PA-PLGA NPs suppressed caspase-3 expression.
33405649	3	79	theme	spherical	763:771	arg1	structure					773:781	a spherical structure	761:781	a spherical structure	761:781	Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation.
29688689	1	0	theme	satisfied	323:331	arg1	catalysts					344:352	satisfied solid base catalysts	323:352	satisfied solid base catalysts	323:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	2	1	theme	catalytic	531:539	arg1	conditions					541:550	catalytic conditions	531:550	catalytic conditions	531:550	To gain the strong basicity, the previous strategy was to basify oxides with alkaline metals to create surficial vacancies or defects, which suffers from the instability under catalytic conditions.
29688689	1	2	theme	Heterogeneous	149:161	arg1	catalysis					174:182	Heterogeneous solid base catalysis	149:182	Heterogeneous solid base catalysis	149:182	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	7	3	theme	several	1041:1047	arg1	bases					1069:1073	several monocomponent solid bases	1041:1073	several monocomponent solid bases	1041:1073	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	2	4	theme	surficial	458:466	arg1	vacancies					468:476	surficial vacancies	458:476	surficial vacancies	458:476	To gain the strong basicity, the previous strategy was to basify oxides with alkaline metals to create surficial vacancies or defects, which suffers from the instability under catalytic conditions.
29688689	1	5	theme	solid	333:337	arg1	catalysts					344:352	satisfied solid base catalysts	323:352	satisfied solid base catalysts	323:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	1	6	theme	solid	163:167	arg1	catalysis					174:182	Heterogeneous solid base catalysis	149:182	Heterogeneous solid base catalysis	149:182	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	7	7	contain	has	1128:1130	arg2	efficiency					1214:1223	the highest catalytic efficiency	1192:1223	the highest catalytic efficiency	1192:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	7	contain	has	1128:1130	arg2	centers					1166:1172	strong base centers	1154:1172	strong base centers (23.1 μmol/g)	1154:1186	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	7	contain	has	1128:1130	arg1	Ga4B2O9					1120:1126	Ga4B2O9	1120:1126	Ga4B2O9	1120:1126	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	7	contain	has	1128:1130	arg2	μmol/g					1180:1185	23.1 μmol/g	1175:1185	23.1 μmol/g	1175:1185	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	7	contain	has	1128:1130	arg2	amount					1144:1149	the largest amount	1132:1149	the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency	1132:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	6	8	theme	α-aminonitriles	990:1004	arg1	synthesis					977:985	the base-catalyzed synthesis	958:985	the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	958:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	7	9	theme	monocomponent	1049:1061	arg1	bases					1069:1073	several monocomponent solid bases	1041:1073	several monocomponent solid bases	1041:1073	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	1	10	theme	base	339:342	arg1	catalysts					344:352	satisfied solid base catalysts	323:352	satisfied solid base catalysts	323:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	0	11	dep	Reaction	100:107	arg1	the					87:89	the	87:89	the	87:89	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	8	12	from	applicable	1242:1251	arg1	catalysis					1283:1291	high-temperature solid-gas catalysis	1256:1291	high-temperature solid-gas catalysis	1256:1291	Ga4B2O9 is also applicable in high-temperature solid-gas catalysis, for example, Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol, resulting in a high selectivity to propanal (79%).
29688689	1	13	theme	catalysts	344:352	arg1	lack					315:318	the lack	311:318	the lack of satisfied solid base catalysts	311:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	9	14	theme	Brönsted	1488:1495	arg1	borate					1459:1464	the comparison gallium borate	1436:1464	the comparison gallium borate	1436:1464	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	9	14	theme	Brönsted	1488:1495	arg1	acid					1497:1500	a Brönsted acid	1486:1500	a Brönsted acid	1486:1500	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	3	15	from	ability	648:654	arg1	stable					603:608	stable	603:608	stable	603:608	Monocomponent basic oxides like MgO are literally stable but deficient in electron-withdrawing ability.
29688689	4	16	theme	Lewis	726:730	arg1	basicity					732:739	the Lewis basicity	722:739	the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9	722:796	Here we prove that a special connectivity of atoms could enhance the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9.
29688689	7	17	theme	Strecker	1097:1104	arg1	reaction					1106:1113	the Strecker reaction	1093:1113	the Strecker reaction	1093:1113	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	8	18	from	catalysis	1283:1291	arg1	applicable					1242:1251	applicable	1242:1251	applicable	1242:1251	Ga4B2O9 is also applicable in high-temperature solid-gas catalysis, for example, Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol, resulting in a high selectivity to propanal (79%).
29688689	8	19	theme	n-propanol	1360:1369	arg1	dehydrogenation					1341:1355	the dehydrogenation	1337:1355	the dehydrogenation of n-propanol	1337:1369	Ga4B2O9 is also applicable in high-temperature solid-gas catalysis, for example, Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol, resulting in a high selectivity to propanal (79%).
29688689	3	20	from	stable	603:608	arg1	ability					648:654	electron-withdrawing ability	627:654	electron-withdrawing ability	627:654	Monocomponent basic oxides like MgO are literally stable but deficient in electron-withdrawing ability.
29688689	1	21	theme	base	169:172	arg1	catalysis					174:182	Heterogeneous solid base catalysis	149:182	Heterogeneous solid base catalysis	149:182	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	0	22	theme	Strecker	91:98	arg1	Reaction					100:107	Strecker Reaction	91:107	Strecker Reaction	91:107	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	6	23	from	synthesis	977:985	arg1	yield					942:946	a high yield	935:946	a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	935:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	8	24	dep	applicable	1242:1251	arg1	Ga4B2O9					1307:1313	Ga4B2O9	1307:1313	Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol	1307:1369	Ga4B2O9 is also applicable in high-temperature solid-gas catalysis, for example, Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol, resulting in a high selectivity to propanal (79%).
29688689	0	25	theme	Lewis	7:11	arg1	Ga4B2O9					18:24	Strong Lewis Base Ga4B2O9	0:24	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.	0:147	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	7	26	theme	highest	1196:1202	arg1	efficiency					1214:1223	the highest catalytic efficiency	1192:1223	the highest catalytic efficiency	1192:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	3	27	theme	Monocomponent	553:565	arg1	oxides					573:578	Monocomponent basic oxides	553:578	Monocomponent basic oxides like MgO	553:587	Monocomponent basic oxides like MgO are literally stable but deficient in electron-withdrawing ability.
29688689	7	28	theme	centers	1166:1172	arg1	amount					1144:1149	the largest amount	1132:1149	the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency	1132:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	28	theme	centers	1166:1172	arg1	centers					1166:1172	strong base centers	1154:1172	strong base centers (23.1 μmol/g)	1154:1186	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	28	theme	centers	1166:1172	arg1	μmol/g					1180:1185	23.1 μmol/g	1175:1185	23.1 μmol/g	1175:1185	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	28	theme	centers	1166:1172	arg1	efficiency					1214:1223	the highest catalytic efficiency	1192:1223	the highest catalytic efficiency	1192:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	2	29	theme	strong	367:372	arg1	basicity					374:381	the strong basicity	363:381	the strong basicity	363:381	To gain the strong basicity, the previous strategy was to basify oxides with alkaline metals to create surficial vacancies or defects, which suffers from the instability under catalytic conditions.
29688689	0	30	theme	Strong	0:5	arg1	Ga4B2O9					18:24	Strong Lewis Base Ga4B2O9	0:24	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.	0:147	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	6	31	theme	base-catalyzed	962:975	arg1	synthesis					977:985	the base-catalyzed synthesis	958:985	the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	958:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	4	32	from	basicity	732:739	arg1	solids					768:773	monocomponent solids	754:773	monocomponent solids exemplified by Ga4B2O9	754:796	Here we prove that a special connectivity of atoms could enhance the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9.
29688689	3	33	theme	basic	567:571	arg1	oxides					573:578	Monocomponent basic oxides	553:578	Monocomponent basic oxides like MgO	553:587	Monocomponent basic oxides like MgO are literally stable but deficient in electron-withdrawing ability.
29688689	7	34	theme	strong	1154:1159	arg1	centers					1166:1172	strong base centers	1154:1172	strong base centers (23.1 μmol/g)	1154:1186	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	34	theme	strong	1154:1159	arg1	μmol/g					1180:1185	23.1 μmol/g	1175:1185	23.1 μmol/g	1175:1185	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	1	35	theme	solid	283:287	arg1	catalysis					294:302	solid acid catalysis	283:302	solid acid catalysis due to the lack of satisfied solid base catalysts	283:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	0	36	theme	Catalytic	113:121	arg1	Conversion					123:132	Catalytic Conversion	113:132	Catalytic Conversion	113:132	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	4	37	theme	oxygen	744:749	arg1	basicity					732:739	the Lewis basicity	722:739	the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9	722:796	Here we prove that a special connectivity of atoms could enhance the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9.
29688689	0	38	theme	Base	13:16	arg1	Ga4B2O9					18:24	Strong Lewis Base Ga4B2O9	0:24	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.	0:147	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	1	39	theme	acid	289:292	arg1	catalysis					294:302	solid acid catalysis	283:302	solid acid catalysis due to the lack of satisfied solid base catalysts	283:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	6	40	from	%	953:953	arg1	synthesis					977:985	the base-catalyzed synthesis	958:985	the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	958:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	9	41	theme	dehydration	1529:1539	arg1	process					1541:1547	the dehydration process	1525:1547	the dehydration process to obtain propylene with a selectivity of 94%	1525:1593	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	9	42	theme	comparison	1440:1449	arg1	acid					1497:1500	a Brönsted acid	1486:1500	a Brönsted acid	1486:1500	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	9	42	theme	comparison	1440:1449	arg1	Ga-PKU-1					1467:1474	Ga-PKU-1	1467:1474	Ga-PKU-1	1467:1474	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	9	42	theme	comparison	1440:1449	arg1	borate					1459:1464	the comparison gallium borate	1436:1464	the comparison gallium borate	1436:1464	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	0	43	theme	Ga-O	27:30	arg1	Connectivity					32:43	Ga-O Connectivity	27:43	Ga-O Connectivity	27:43	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	6	44	theme	%	953:953	arg1	yield					942:946	a high yield	935:946	a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	935:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	7	45	theme	solid	1063:1067	arg1	bases					1069:1073	several monocomponent solid bases	1041:1073	several monocomponent solid bases	1041:1073	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	8	46	theme	solid-gas	1273:1281	arg1	catalysis					1283:1291	high-temperature solid-gas catalysis	1256:1291	high-temperature solid-gas catalysis	1256:1291	Ga4B2O9 is also applicable in high-temperature solid-gas catalysis, for example, Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol, resulting in a high selectivity to propanal (79%).
29688689	2	47	theme	previous	388:395	arg1	strategy					397:404	the previous strategy	384:404	the previous strategy	384:404	To gain the strong basicity, the previous strategy was to basify oxides with alkaline metals to create surficial vacancies or defects, which suffers from the instability under catalytic conditions.
29688689	1	48	theme	due	304:306	arg1	catalysis					294:302	solid acid catalysis	283:302	solid acid catalysis due to the lack of satisfied solid base catalysts	283:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	1	49	dep	industry	222:229	arg1	developed					261:269	developed	261:269	is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts	243:352	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	8	50	theme	high	1387:1390	arg1	selectivity					1392:1402	a high selectivity	1385:1402	a high selectivity to propanal (79%)	1385:1420	Ga4B2O9 is also applicable in high-temperature solid-gas catalysis, for example, Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol, resulting in a high selectivity to propanal (79%).
29688689	1	51	theme	chemical	213:220	arg1	industry					222:229	chemical industry	213:229	chemical industry	213:229	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	6	52	from	yield	942:946	arg1	synthesis					977:985	the base-catalyzed synthesis	958:985	the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	958:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	3	53	theme	electron-withdrawing	627:646	arg1	ability					648:654	electron-withdrawing ability	627:654	electron-withdrawing ability	627:654	Monocomponent basic oxides like MgO are literally stable but deficient in electron-withdrawing ability.
29688689	9	54	theme	gallium	1451:1457	arg1	acid					1497:1500	a Brönsted acid	1486:1500	a Brönsted acid	1486:1500	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	9	54	theme	gallium	1451:1457	arg1	Ga-PKU-1					1467:1474	Ga-PKU-1	1467:1474	Ga-PKU-1	1467:1474	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	9	54	theme	gallium	1451:1457	arg1	borate					1459:1464	the comparison gallium borate	1436:1464	the comparison gallium borate	1436:1464	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	6	55	with	catalyst	921:928	arg1	yield					942:946	a high yield	935:946	a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	935:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	2	56	theme	alkaline	432:439	arg1	metals					441:446	alkaline metals	432:446	alkaline metals	432:446	To gain the strong basicity, the previous strategy was to basify oxides with alkaline metals to create surficial vacancies or defects, which suffers from the instability under catalytic conditions.
29688689	0	57	theme	n-Propanol	137:146	arg1	Conversion					123:132	Catalytic Conversion	113:132	Catalytic Conversion	113:132	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	0	57	theme	n-Propanol	137:146	arg1	Reaction					100:107	Strecker Reaction	91:107	Strecker Reaction	91:107	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	4	58	theme	atoms	702:706	arg1	connectivity					686:697	a special connectivity	676:697	a special connectivity of atoms	676:706	Here we prove that a special connectivity of atoms could enhance the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9.
29688689	6	59	theme	high	937:940	arg1	yield					942:946	a high yield	935:946	a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	935:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	1	60	from	industry	222:229	arg1	valuable					187:194	valuable	187:194	valuable	187:194	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	0	61	dep	Ga4B2O9	18:24	arg1	Enhanced					45:52	Enhanced	45:52	Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol	45:146	Strong Lewis Base Ga4B2O9: Ga-O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of n-Propanol.
29688689	2	62	with	oxides	420:425	arg1	metals					441:446	alkaline metals	432:446	alkaline metals	432:446	To gain the strong basicity, the previous strategy was to basify oxides with alkaline metals to create surficial vacancies or defects, which suffers from the instability under catalytic conditions.
29688689	8	63	theme	high-temperature	1256:1271	arg1	catalysis					1283:1291	high-temperature solid-gas catalysis	1256:1291	high-temperature solid-gas catalysis	1256:1291	Ga4B2O9 is also applicable in high-temperature solid-gas catalysis, for example, Ga4B2O9 catalyzed efficiently the dehydrogenation of n-propanol, resulting in a high selectivity to propanal (79%).
29688689	7	64	theme	largest	1136:1142	arg1	amount					1144:1149	the largest amount	1132:1149	the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency	1132:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	64	theme	largest	1136:1142	arg1	centers					1166:1172	strong base centers	1154:1172	strong base centers (23.1 μmol/g)	1154:1186	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	64	theme	largest	1136:1142	arg1	μmol/g					1180:1185	23.1 μmol/g	1175:1185	23.1 μmol/g	1175:1185	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	64	theme	largest	1136:1142	arg1	efficiency					1214:1223	the highest catalytic efficiency	1192:1223	the highest catalytic efficiency	1192:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	4	65	theme	monocomponent	754:766	arg1	solids					768:773	monocomponent solids	754:773	monocomponent solids exemplified by Ga4B2O9	754:796	Here we prove that a special connectivity of atoms could enhance the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9.
29688689	9	66	theme	%	1593:1593	arg1	selectivity					1576:1586	a selectivity	1574:1586	a selectivity of 94%	1574:1593	In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%.
29688689	7	67	theme	catalytic	1204:1212	arg1	efficiency					1214:1223	the highest catalytic efficiency	1192:1223	the highest catalytic efficiency	1192:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	5	68	attach	linked	847:852	arg2	basicity					821:828	The structure-induced basicity	799:828	The structure-induced basicity	799:828	The structure-induced basicity is from the μ3-O linked exclusively to five-coordinated Ga3+.
29688689	5	68	attach	linked	847:852	arg1	Ga3+					886:889	Ga3+	886:889	Ga3+	886:889	The structure-induced basicity is from the μ3-O linked exclusively to five-coordinated Ga3+.
29688689	1	69	from	valuable	187:194	arg1	industry					222:229	chemical industry	213:229	chemical industry	213:229	Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts.
29688689	4	70	theme	special	678:684	arg1	connectivity					686:697	a special connectivity	676:697	a special connectivity of atoms	676:706	Here we prove that a special connectivity of atoms could enhance the Lewis basicity of oxygen in monocomponent solids exemplified by Ga4B2O9.
29688689	6	71	theme	durable	913:919	arg1	catalyst					921:928	a durable catalyst	911:928	a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction	911:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
29688689	7	72	theme	efficiency	1214:1223	arg1	amount					1144:1149	the largest amount	1132:1149	the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency	1132:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	72	theme	efficiency	1214:1223	arg1	centers					1166:1172	strong base centers	1154:1172	strong base centers (23.1 μmol/g)	1154:1186	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	72	theme	efficiency	1214:1223	arg1	μmol/g					1180:1185	23.1 μmol/g	1175:1185	23.1 μmol/g	1175:1185	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	72	theme	efficiency	1214:1223	arg1	efficiency					1214:1223	the highest catalytic efficiency	1192:1223	the highest catalytic efficiency	1192:1223	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	73	theme	base	1161:1164	arg1	centers					1166:1172	strong base centers	1154:1172	strong base centers (23.1 μmol/g)	1154:1186	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	7	73	theme	base	1161:1164	arg1	μmol/g					1180:1185	23.1 μmol/g	1175:1185	23.1 μmol/g	1175:1185	In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga4B2O9 has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency.
29688689	5	74	theme	structure-induced	803:819	arg1	basicity					821:828	The structure-induced basicity	799:828	The structure-induced basicity	799:828	The structure-induced basicity is from the μ3-O linked exclusively to five-coordinated Ga3+.
29688689	6	75	theme	Strecker	1009:1016	arg1	reaction					1018:1025	Strecker reaction	1009:1025	Strecker reaction	1009:1025	Ga4B2O9 behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction.
30927711	5	0	link	O-linked	905:912	arg1	transferase					934:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	2	1	theme	hMPV	348:351	arg1	infection					353:361	hMPV infection	348:361	hMPV infection of airway epithelial cells (AECs)	348:395	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	5	2	from	reduction	967:975	arg1	titer					985:989	hMPV titer	980:989	hMPV titer	980:989	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	1	3	theme	immunocompromised	233:249	arg1	individuals					251:261	immunocompromised individuals	233:261	immunocompromised individuals	233:261	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	3	theme	immunocompromised	233:249	arg1	infants					212:218	infants	212:218	infants	212:218	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	4	theme	important	149:157	arg1	cause					159:163	an important cause	146:163	an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals	146:261	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	4	theme	important	149:157	arg1	metapneumovirus					120:134	Human metapneumovirus	114:134	Human metapneumovirus (hMPV)	114:141	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	5	5	theme	O-linked	905:912	arg1	transferase					934:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	0	6	theme	metabolic	94:102	arg1	pathways					104:111	core metabolic pathways	89:111	core metabolic pathways	89:111	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	5	7	theme	hMPV	980:983	arg1	titer					985:989	hMPV titer	980:989	hMPV titer	980:989	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	2	8	theme	microarrays	294:304	arg1	data					306:309	microarrays data	294:309	microarrays data	294:309	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	3	9	theme	dehydrogenase	526:538	arg1	enzymes					472:478	the glycolytic pathway enzymes	449:478	the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	449:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	9	theme	dehydrogenase	526:538	arg1	A					540:540	lactate dehydrogenase A	518:540	lactate dehydrogenase A	518:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	0	10	theme	core	89:92	arg1	pathways					104:111	core metabolic pathways	89:111	core metabolic pathways	89:111	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	3	11	theme	glycosylation	689:701	arg1	pathways					703:710	the hexosamine biosynthetic and glycosylation pathways	657:710	pathways	703:710	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	5	12	theme	enzyme	898:903	arg1	transferase					934:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	3	13	theme	pathway	464:470	arg1	enzymes					472:478	the glycolytic pathway enzymes	449:478	the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	449:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	13	theme	pathway	464:470	arg1	A					540:540	lactate dehydrogenase A	518:540	lactate dehydrogenase A	518:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	13	theme	pathway	464:470	arg1	M2					510:511	pyruvate kinase M2	494:511	pyruvate kinase M2	494:511	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	13	theme	pathway	464:470	arg1	hexokinase					480:489	hexokinase 2	480:491	hexokinase 2	480:491	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	4	14	theme	acid	805:808	arg1	cycle					810:814	the tricarboxylic acid cycle	787:814	the tricarboxylic acid cycle	787:814	On the other hand, expression of the majority of the enzymes belonging to the tricarboxylic acid cycle was significantly diminished.
30927711	3	15	theme	kinase	503:508	arg1	enzymes					472:478	the glycolytic pathway enzymes	449:478	the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	449:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	15	theme	kinase	503:508	arg1	M2					510:511	pyruvate kinase M2	494:511	pyruvate kinase M2	494:511	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	2	16	theme	epithelial	373:382	arg1	cells					384:388	airway epithelial cells	366:388	airway epithelial cells (AECs)	366:395	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	2	16	theme	epithelial	373:382	arg1	AECs					391:394	AECs	391:394	AECs	391:394	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	5	17	theme	virus	1081:1085	arg1	cycle					1092:1096	the virus life cycle	1077:1096	the virus life cycle	1077:1096	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	4	18	theme	tricarboxylic	791:803	arg1	cycle					810:814	the tricarboxylic acid cycle	787:814	the tricarboxylic acid cycle	787:814	On the other hand, expression of the majority of the enzymes belonging to the tricarboxylic acid cycle was significantly diminished.
30927711	2	19	theme	pathway	274:280	arg1	analysis					282:289	Ingenuity pathway analysis	264:289	Ingenuity pathway analysis of microarrays data	264:309	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	2	20	theme	cells	384:388	arg1	infection					353:361	hMPV infection	348:361	hMPV infection of airway epithelial cells (AECs)	348:395	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	0	21	theme	metapneumovirus	6:20	arg1	infection					22:30	Human metapneumovirus infection	0:30	Human metapneumovirus infection of airway epithelial cells	0:57	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	5	22	theme	life	1087:1090	arg1	cycle					1092:1096	the virus life cycle	1077:1096	the virus life cycle	1077:1096	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	5	23	theme	transferase	934:944	arg1	Inhibition					846:855	Inhibition	846:855	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase	846:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	5	24	dep	potential	1124:1132	arg1	antiviral					1134:1142	antiviral	1134:1142	antiviral	1134:1142	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	1	25	theme	acute	168:172	arg1	infections					198:207	acute lower respiratory tract infections	168:207	acute lower respiratory tract infections	168:207	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	0	26	theme	Human	0:4	arg1	infection					22:30	Human metapneumovirus infection	0:30	Human metapneumovirus infection of airway epithelial cells	0:57	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	5	27	theme	N-acetylglucosamine	914:932	arg1	transferase					934:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	2	28	theme	airway	366:371	arg1	cells					384:388	airway epithelial cells	366:388	airway epithelial cells (AECs)	366:395	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	2	28	theme	airway	366:371	arg1	AECs					391:394	AECs	391:394	AECs	391:394	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	3	29	theme	lactate	518:524	arg1	enzymes					472:478	the glycolytic pathway enzymes	449:478	the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	449:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	29	theme	lactate	518:524	arg1	A					540:540	lactate dehydrogenase A	518:540	lactate dehydrogenase A	518:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	1	30	theme	respiratory	180:190	arg1	infections					198:207	acute lower respiratory tract infections	168:207	acute lower respiratory tract infections	168:207	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	5	31	theme	significant	955:965	arg1	reduction					967:975	a significant reduction	953:975	a significant reduction in hMPV titer	953:989	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	2	32	theme	data	306:309	arg1	analysis					282:289	Ingenuity pathway analysis	264:289	Ingenuity pathway analysis of microarrays data	264:309	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	1	33	theme	tract	192:196	arg1	infections					198:207	acute lower respiratory tract infections	168:207	acute lower respiratory tract infections	168:207	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	0	34	theme	epithelial	42:51	arg1	cells					53:57	airway epithelial cells	35:57	airway epithelial cells	35:57	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	3	35	theme	enzymes	472:478	arg1	levels					439:444	levels	439:444	levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	439:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	0	36	from	changes	78:84	arg1	pathways					104:111	core metabolic pathways	89:111	core metabolic pathways	89:111	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	1	37	dep	acute	168:172	arg1	lower					174:178	lower	174:178	lower	174:178	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	38	theme	infections	198:207	arg1	cause					159:163	an important cause	146:163	an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals	146:261	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	38	theme	infections	198:207	arg1	metapneumovirus					120:134	Human metapneumovirus	114:134	Human metapneumovirus (hMPV)	114:141	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	0	39	theme	airway	35:40	arg1	cells					53:57	airway epithelial cells	35:57	airway epithelial cells	35:57	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	5	40	gly	glycosylating	884:896	arg0	transferase					934:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	5	41	theme	major	1059:1063	arg1	role					1065:1068	a major role	1057:1068	a major role	1057:1068	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	3	42	theme	normal	576:581	arg1	AECs					589:592	normal human AECs	576:592	normal human AECs	576:592	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	5	43	theme	metabolic	1008:1016	arg1	targets					1144:1150	potential antiviral targets	1124:1150	potential antiviral targets	1124:1150	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	5	43	theme	metabolic	1008:1016	arg1	changes					1018:1024	metabolic changes	1008:1024	metabolic changes induced by hMPV infection	1008:1050	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	1	44	theme	Human	114:118	arg1	cause					159:163	an important cause	146:163	an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals	146:261	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	44	theme	Human	114:118	arg1	hMPV					137:140	hMPV	137:140	hMPV	137:140	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	44	theme	Human	114:118	arg1	metapneumovirus					120:134	Human metapneumovirus	114:134	Human metapneumovirus (hMPV)	114:141	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	0	45	theme	cells	53:57	arg1	infection					22:30	Human metapneumovirus infection	0:30	Human metapneumovirus infection of airway epithelial cells	0:57	Human metapneumovirus infection of airway epithelial cells is associated with changes in core metabolic pathways.
30927711	2	46	theme	genes	330:334	arg1	genes					330:334	genes	330:334	genes affected by hMPV infection of airway epithelial cells (AECs)	330:395	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	2	46	theme	genes	330:334	arg1	%					325:325	20%	323:325	20% of genes affected by hMPV infection of airway epithelial cells (AECs)	323:395	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	5	47	theme	potential	1124:1132	arg1	targets					1144:1150	potential antiviral targets	1124:1150	potential antiviral targets	1124:1150	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	5	47	theme	potential	1124:1132	arg1	changes					1018:1024	metabolic changes	1008:1024	metabolic changes induced by hMPV infection	1008:1050	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	3	48	theme	enzymes	636:642	arg1	levels					626:631	levels	626:631	levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways	626:710	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	48	theme	enzymes	636:642	arg1	infection					604:612	hMPV infection	599:612	hMPV infection	599:612	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	2	49	theme	Ingenuity	264:272	arg1	analysis					282:289	Ingenuity pathway analysis	264:289	Ingenuity pathway analysis of microarrays data	264:309	Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism.
30927711	4	50	theme	enzymes	766:772	arg1	majority					750:757	the majority	746:757	the majority of the enzymes belonging to the tricarboxylic acid cycle	746:814	On the other hand, expression of the majority of the enzymes belonging to the tricarboxylic acid cycle was significantly diminished.
30927711	5	51	theme	glycosylating	884:896	arg1	transferase					934:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	the glycosylating enzyme O-linked N-acetylglucosamine transferase	880:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	4	52	theme	other	720:724	arg1	hand					726:729	the other hand	716:729	the other hand	716:729	On the other hand, expression of the majority of the enzymes belonging to the tricarboxylic acid cycle was significantly diminished.
30927711	3	53	dep	enzymes	472:478	arg1	enzymes					472:478	the glycolytic pathway enzymes	449:478	the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	449:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	53	dep	enzymes	472:478	arg1	A					540:540	lactate dehydrogenase A	518:540	lactate dehydrogenase A	518:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	53	dep	enzymes	472:478	arg1	M2					510:511	pyruvate kinase M2	494:511	pyruvate kinase M2	494:511	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	53	dep	enzymes	472:478	arg1	hexokinase					480:489	hexokinase 2	480:491	hexokinase 2	480:491	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	5	54	theme	hMPV	1037:1040	arg1	infection					1042:1050	hMPV infection	1037:1050	hMPV infection	1037:1050	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	3	55	theme	hMPV	599:602	arg1	infection					604:612	hMPV infection	599:612	hMPV infection	599:612	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	56	theme	glycolytic	453:462	arg1	enzymes					472:478	the glycolytic pathway enzymes	449:478	the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	449:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	56	theme	glycolytic	453:462	arg1	A					540:540	lactate dehydrogenase A	518:540	lactate dehydrogenase A	518:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	56	theme	glycolytic	453:462	arg1	M2					510:511	pyruvate kinase M2	494:511	pyruvate kinase M2	494:511	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	56	theme	glycolytic	453:462	arg1	hexokinase					480:489	hexokinase 2	480:491	hexokinase 2	480:491	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	4	57	theme	majority	750:757	arg1	expression					732:741	expression	732:741	expression of the majority of the enzymes belonging to the tricarboxylic acid cycle	732:814	On the other hand, expression of the majority of the enzymes belonging to the tricarboxylic acid cycle was significantly diminished.
30927711	3	58	theme	human	583:587	arg1	AECs					589:592	normal human AECs	576:592	normal human AECs	576:592	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	5	59	theme	hexokinase	860:869	arg1	Inhibition					846:855	Inhibition	846:855	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase	846:944	Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
30927711	1	60	from	cause	159:163	arg1	elderly					221:227	elderly	221:227	elderly	221:227	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	60	from	cause	159:163	arg1	individuals					251:261	immunocompromised individuals	233:261	immunocompromised individuals	233:261	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	1	60	from	cause	159:163	arg1	infants					212:218	infants	212:218	infants	212:218	Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals.
30927711	3	61	theme	pyruvate	494:501	arg1	enzymes					472:478	the glycolytic pathway enzymes	449:478	the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A	449:540	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30927711	3	61	theme	pyruvate	494:501	arg1	M2					510:511	pyruvate kinase M2	494:511	pyruvate kinase M2	494:511	We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways.
30296064	7	0	theme	metabolic	1131:1139	arg1	strategy					1149:1156	This one-step metabolic feeding strategy	1117:1156	This one-step metabolic feeding strategy	1117:1156	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	4	1	theme	uridine	594:600	arg1	analogues					649:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues	582:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore	582:749	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	2	2	theme	Metabolic	290:298	arg1	strategies					309:318	Metabolic labeling strategies	290:318	Metabolic labeling strategies to monitor O-GlcNAcylation in cells	290:354	Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
30296064	1	3	theme	cellular	269:276	arg1	physiology					278:287	cellular physiology	269:287	cellular physiology	269:287	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	9	4	theme	pulse	1713:1717	arg1	experiments					1725:1735	two-color pulse chase experiments	1703:1735	two-color pulse chase experiments	1703:1735	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	4	5	theme	N-acyl	672:677	arg1	glucosamine					688:698	glucosamine	688:698	glucosamine	688:698	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	4	5	theme	N-acyl	672:677	arg1	group					679:683	the N-acyl group	668:683	the N-acyl group of glucosamine	668:698	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	0	6	theme	Direct	0:5	arg1	Labeling					28:35	Direct One-Step Fluorescent Labeling	0:35	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells	0:79	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	1	7	theme	O-GlcNAc	201:208	arg1	OGT					223:225	OGT	223:225	OGT	223:225	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	1	7	theme	O-GlcNAc	201:208	arg1	transferase					210:220	enzyme O-GlcNAc transferase	194:220	the enzyme O-GlcNAc transferase (OGT)	190:226	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	7	8	with	proteins	1193:1200	arg1	conjugate					1264:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate	1207:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner	1207:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	4	9	theme	analogues	649:657	arg1	creation					570:577	the creation	566:577	the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore	566:749	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	5	10	theme	activity	838:845	arg1	monitoring					820:829	direct monitoring	813:829	direct monitoring of OGT activity on protein substrates	813:867	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	8	11	theme	cellular	1476:1483	arg1	physiology					1485:1494	cellular physiology	1476:1494	cellular physiology	1476:1494	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	5	12	theme	protein	850:856	arg1	substrates					858:867	protein substrates	850:867	protein substrates	850:867	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	9	13	theme	specific	1768:1775	arg1	substrates					1785:1794	specific protein substrates	1768:1794	specific protein substrates in live cells	1768:1808	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	4	14	theme	suitable	719:726	arg1	linker					728:733	a suitable linker	717:733	a suitable linker	717:733	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	1	15	theme	proteins	132:139	arg1	modification					116:127	The modification	112:127	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT)	112:226	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	6	16	theme	fluorescent	927:937	arg1	precursor					949:957	a corresponding fluorescent metabolic precursor	911:957	a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP)	911:1020	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	1	17	theme	O-linked	146:153	arg1	O-GlcNAc					177:184	O-GlcNAc	177:184	O-GlcNAc	177:184	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	1	17	theme	O-linked	146:153	arg1	N-acetylglucosamine					155:173	O-linked N-acetylglucosamine	146:173	O-linked N-acetylglucosamine ( O-GlcNAc)	146:185	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	9	18	theme	live	1799:1802	arg1	cells					1804:1808	live cells	1799:1808	live cells	1799:1808	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	8	19	theme	cells	1363:1367	arg1	engineering					1348:1358	no genetic engineering	1337:1358	no genetic engineering of cells	1337:1367	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	0	20	theme	Live	70:73	arg1	Cells					75:79	Live Cells	70:79	Live Cells	70:79	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	7	21	theme	O-GlcNAcylated	1178:1191	arg1	proteins					1193:1200	O-GlcNAcylated proteins	1178:1200	O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner	1178:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	8	22	theme	improved	1518:1525	arg1	understanding					1527:1539	an improved understanding	1515:1539	an improved understanding of the regulation of OGT within cells	1515:1577	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	2	23	from	O-GlcNAcylation	331:345	arg1	cells					350:354	cells	350:354	cells	350:354	Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
30296064	6	24	theme	biosynthetic	995:1006	arg1	HBP					1017:1019	HBP	1017:1019	HBP	1017:1019	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	6	24	theme	biosynthetic	995:1006	arg1	pathway					1008:1014	the hexosamine biosynthetic pathway	980:1014	the hexosamine biosynthetic pathway (HBP)	980:1020	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	5	25	from	monitoring	820:829	arg1	substrates					858:867	protein substrates	850:867	protein substrates	850:867	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	8	26	theme	regulation	1548:1557	arg1	understanding					1527:1539	an improved understanding	1515:1539	an improved understanding of the regulation of OGT within cells	1515:1577	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	5	27	theme	human	758:762	arg1	OGT					764:766	human OGT	758:766	human OGT	758:766	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	9	28	theme	further	1584:1590	arg1	expansion					1592:1600	The further expansion	1580:1600	The further expansion of this one-step in-cell labeling strategy	1580:1643	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	8	29	theme	OGT	1562:1564	arg1	regulation					1548:1557	the regulation	1544:1557	the regulation of OGT within cells	1544:1577	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	5	30	theme	direct	813:818	arg1	monitoring					820:829	direct monitoring	813:829	direct monitoring of OGT activity on protein substrates	813:867	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	1	31	theme	physiology	278:287	arg1	regulator					256:264	an important regulator	243:264	an important regulator of cellular physiology	243:287	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	1	32	with	proteins	132:139	arg1	O-GlcNAc					177:184	O-GlcNAc	177:184	O-GlcNAc	177:184	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	1	32	with	proteins	132:139	arg1	N-acetylglucosamine					155:173	O-linked N-acetylglucosamine	146:173	O-linked N-acetylglucosamine ( O-GlcNAc)	146:185	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	0	33	theme	Fluorescent	16:26	arg1	Labeling					28:35	Direct One-Step Fluorescent Labeling	0:35	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells	0:79	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	9	34	theme	one-step	1610:1617	arg1	strategy					1636:1643	this one-step in-cell labeling strategy	1605:1643	this one-step in-cell labeling strategy	1605:1643	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	6	35	theme	metabolic	1035:1043	arg1	assimilation					1045:1056	its metabolic assimilation	1031:1056	its metabolic assimilation	1031:1056	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	9	36	from	activity	1756:1763	arg1	substrates					1785:1794	specific protein substrates	1768:1794	specific protein substrates in live cells	1768:1808	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	2	37	theme	O-GlcNAc	421:428	arg1	roles					412:416	the molecular roles	398:416	the molecular roles of O-GlcNAc	398:428	Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
30296064	3	38	theme	labeling	465:472	arg1	procedures					474:483	two-step labeling procedures	456:483	two-step labeling procedures	456:483	These strategies rely on two-step labeling procedures, which limits the scope of experiments that can be performed.
30296064	5	39	theme	donor	783:787	arg1	substrates					795:804	these donor sugar substrates	777:804	these donor sugar substrates	777:804	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	9	40	theme	labeling	1627:1634	arg1	strategy					1636:1643	this one-step in-cell labeling strategy	1605:1643	this one-step in-cell labeling strategy	1605:1643	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	0	41	theme	Proteins	58:65	arg1	Labeling					28:35	Direct One-Step Fluorescent Labeling	0:35	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells	0:79	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	7	42	theme	dose-dependent	1306:1319	arg1	manner					1321:1326	a time- and dose-dependent manner	1294:1326	a time- and dose-dependent manner	1294:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	4	43	theme	5'-diphospho-	602:614	arg1	analogues					649:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues	582:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore	582:749	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	5	44	theme	sugar	789:793	arg1	substrates					795:804	these donor sugar substrates	777:804	these donor sugar substrates	777:804	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	6	45	theme	corresponding	913:925	arg1	precursor					949:957	a corresponding fluorescent metabolic precursor	911:957	a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP)	911:1020	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	7	46	theme	time-	1296:1300	arg1	manner					1321:1326	a time- and dose-dependent manner	1294:1326	a time- and dose-dependent manner	1294:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	7	47	theme	GlcN-NBD	1254:1261	arg1	conjugate					1264:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate	1207:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner	1207:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	7	48	theme	one-step	1122:1129	arg1	strategy					1149:1156	This one-step metabolic feeding strategy	1117:1156	This one-step metabolic feeding strategy	1117:1156	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	2	49	theme	great	371:375	arg1	value					377:381	great value	371:381	great value for uncovering the molecular roles of O-GlcNAc	371:428	Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
30296064	1	50	theme	important	246:254	arg1	regulator					256:264	an important regulator	243:264	an important regulator of cellular physiology	243:287	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	9	51	theme	experiments	1681:1691	arg1	range					1672:1676	a range	1670:1676	a range of experiments including two-color pulse chase experiments	1670:1735	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	6	52	theme	proteins	1089:1096	arg1	labeling					1062:1069	labeling	1062:1069	labeling	1062:1069	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	6	52	theme	proteins	1089:1096	arg1	assimilation					1045:1056	its metabolic assimilation	1031:1056	its metabolic assimilation	1031:1056	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	2	53	theme	labeling	300:307	arg1	strategies					309:318	Metabolic labeling strategies	290:318	Metabolic labeling strategies to monitor O-GlcNAcylation in cells	290:354	Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
30296064	9	54	theme	two-color	1703:1711	arg1	experiments					1725:1735	two-color pulse chase experiments	1703:1735	two-color pulse chase experiments	1703:1735	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	4	55	theme	fluorescent	582:592	arg1	analogues					649:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues	582:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore	582:749	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	9	56	theme	chase	1719:1723	arg1	experiments					1725:1735	two-color pulse chase experiments	1703:1735	two-color pulse chase experiments	1703:1735	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	1	57	theme	enzyme	194:199	arg1	OGT					223:225	OGT	223:225	OGT	223:225	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	1	57	theme	enzyme	194:199	arg1	transferase					210:220	enzyme O-GlcNAc transferase	194:220	the enzyme O-GlcNAc transferase (OGT)	190:226	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	5	58	theme	OGT	834:836	arg1	activity					838:845	OGT activity	834:845	OGT activity	834:845	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	6	59	theme	last	967:970	arg1	step					972:975	the last step	963:975	the last step of the hexosamine biosynthetic pathway (HBP)	963:1020	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	5	60	dep	show	772:775	arg1	permit					806:811	permit	806:811	show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro	772:876	Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro.
30296064	3	61	theme	experiments	512:522	arg1	scope					503:507	the scope	499:507	the scope of experiments that can be performed	499:544	These strategies rely on two-step labeling procedures, which limits the scope of experiments that can be performed.
30296064	8	62	from	roles	1455:1459	arg1	physiology					1485:1494	cellular physiology	1476:1494	cellular physiology	1476:1494	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	6	63	theme	metabolic	939:947	arg1	precursor					949:957	a corresponding fluorescent metabolic precursor	911:957	a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP)	911:1020	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	9	64	theme	protein	1777:1783	arg1	substrates					1785:1794	specific protein substrates	1768:1794	specific protein substrates in live cells	1768:1808	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	2	65	dep	strategies	309:318	arg1	monitor					323:329	monitor	323:329	to monitor O-GlcNAcylation in cells	320:354	Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
30296064	9	66	from	substrates	1785:1794	arg1	cells					1804:1808	live cells	1799:1808	live cells	1799:1808	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	8	67	theme	genetic	1340:1346	arg1	engineering					1348:1358	no genetic engineering	1337:1358	no genetic engineering of cells	1337:1367	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	0	68	from	Labeling	28:35	arg1	Cells					75:79	Live Cells	70:79	Live Cells	70:79	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	4	69	theme	glucosamine	688:698	arg1	glucosamine					688:698	glucosamine	688:698	glucosamine	688:698	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	4	69	theme	glucosamine	688:698	arg1	group					679:683	the N-acyl group	668:683	the N-acyl group of glucosamine	668:698	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	0	70	theme	Metabolic	87:95	arg1	Intermediates					97:109	Metabolic Intermediates	87:109	Metabolic Intermediates	87:109	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	6	71	theme	pathway	1008:1014	arg1	step					972:975	the last step	963:975	the last step of the hexosamine biosynthetic pathway (HBP)	963:1020	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	9	72	theme	OGT	1752:1754	arg1	activity					1756:1763	OGT activity	1752:1763	OGT activity on specific protein substrates in live cells	1752:1808	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	7	73	theme	glucosamine-nitrobenzoxadiazole	1221:1251	arg1	conjugate					1264:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate	1207:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner	1207:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	6	74	theme	hexosamine	984:993	arg1	HBP					1017:1019	HBP	1017:1019	HBP	1017:1019	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	6	74	theme	hexosamine	984:993	arg1	pathway					1008:1014	the hexosamine biosynthetic pathway	980:1014	the hexosamine biosynthetic pathway (HBP)	980:1020	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	6	75	theme	O-GlcNAcylated	1074:1087	arg1	proteins					1089:1096	O-GlcNAcylated proteins	1074:1096	O-GlcNAcylated proteins within live cells	1074:1114	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	2	76	theme	molecular	402:410	arg1	roles					412:416	the molecular roles	398:416	the molecular roles of O-GlcNAc	398:428	Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc.
30296064	0	77	theme	One-Step	7:14	arg1	Labeling					28:35	Direct One-Step Fluorescent Labeling	0:35	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells	0:79	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	0	78	theme	O-GlcNAc-Modified	40:56	arg1	Proteins					58:65	O-GlcNAc-Modified Proteins	40:65	O-GlcNAc-Modified Proteins	40:65	Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates.
30296064	9	79	theme	in-cell	1619:1625	arg1	strategy					1636:1643	this one-step in-cell labeling strategy	1605:1643	this one-step in-cell labeling strategy	1605:1643	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	7	80	theme	fluorescent	1209:1219	arg1	conjugate					1264:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate	1207:1272	a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner	1207:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	7	81	theme	feeding	1141:1147	arg1	strategy					1149:1156	This one-step metabolic feeding strategy	1117:1156	This one-step metabolic feeding strategy	1117:1156	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30296064	9	82	theme	strategy	1636:1643	arg1	expansion					1592:1600	The further expansion	1580:1600	The further expansion of this one-step in-cell labeling strategy	1580:1643	The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
30296064	1	83	link	O-linked	146:153	arg1	O-GlcNAc					177:184	O-GlcNAc	177:184	O-GlcNAc	177:184	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	1	83	link	O-linked	146:153	arg1	N-acetylglucosamine					155:173	O-linked N-acetylglucosamine	146:173	O-linked N-acetylglucosamine ( O-GlcNAc)	146:185	The modification of proteins with O-linked N-acetylglucosamine ( O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology.
30296064	4	84	mod	modified	703:710	arg3	fluorophore					739:749	fluorophore	739:749	fluorophore	739:749	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	4	84	mod	modified	703:710	arg1	glucosamine					688:698	glucosamine	688:698	glucosamine	688:698	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	4	84	mod	modified	703:710	arg1	group					679:683	the N-acyl group	668:683	the N-acyl group of glucosamine	668:698	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	4	84	mod	modified	703:710	arg3	linker					728:733	a suitable linker	717:733	a suitable linker	717:733	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	4	85	theme	N-acetylglucosamine	616:634	arg1	analogues					649:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues	582:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore	582:749	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	6	86	theme	live	1105:1108	arg1	cells					1110:1114	live cells	1105:1114	live cells	1105:1114	We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells.
30296064	3	87	theme	two-step	456:463	arg1	procedures					474:483	two-step labeling procedures	456:483	two-step labeling procedures	456:483	These strategies rely on two-step labeling procedures, which limits the scope of experiments that can be performed.
30296064	4	88	theme	UDP-GlcNAc	637:646	arg1	analogues					649:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues	582:657	fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore	582:749	Here, we report on the creation of fluorescent uridine 5'-diphospho- N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore.
30296064	8	89	theme	O-GlcNAc	1464:1471	arg1	roles					1455:1459	the roles	1451:1459	the roles of O-GlcNAc in cellular physiology	1451:1494	Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells.
30296064	7	90	theme	proteins	1193:1200	arg1	labeling					1166:1173	labeling	1166:1173	labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner	1166:1326	This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner.
30177911	7	0	theme	putative	1181:1188	arg1	proteins					1205:1212	putative O-GlcNAcylated proteins	1181:1212	putative O-GlcNAcylated proteins in Toxoplasma gondii	1181:1233	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	4	1	theme	cytosolic	762:770	arg1	compartments					784:795	the cytosolic and nuclear compartments	758:795	the cytosolic and nuclear compartments	758:795	O-GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments.
30177911	7	2	theme	present	1099:1105	arg1	work					1107:1110	the present work	1095:1110	the present work	1095:1110	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	4	3	theme	O-GlcNAc	632:639	arg1	transferase					641:651	O-GlcNAc transferase	632:651	O-GlcNAc transferase	632:651	O-GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments.
30177911	4	3	theme	O-GlcNAc	632:639	arg1	OGT					656:658	OGT	656:658	OGT	656:658	O-GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments.
30177911	4	3	theme	O-GlcNAc	632:639	arg1	enzyme					667:672	the enzyme	663:672	the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments	663:795	O-GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments.
30177911	10	4	theme	living	1738:1743	arg1	beings					1745:1750	living beings	1738:1750	living beings	1738:1750	Together, these data show that regardless of proteins strictly specific to organisms, O-GlcNAcylated proteins are rather similar among living beings.
30177911	6	5	from	focus	1073:1077	arg1	protists					1082:1089	protists	1082:1089	protists	1082:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	8	6	theme	protein	1395:1401	arg1	organization					1361:1372	cell shape organization	1350:1372	cell shape organization	1350:1372	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	6	theme	protein	1395:1401	arg1	synthesis					1403:1411	protein synthesis	1395:1411	protein synthesis	1395:1411	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	6	7	theme	Numerous	974:981	arg1	studies					983:989	Numerous studies	974:989	Numerous studies	974:989	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	3	8	theme	metabolic	582:590	arg1	diseases					592:599	metabolic diseases	582:599	metabolic diseases	582:599	More and more evidences tend to show that deregulations in the homeostasis of O-GlcNAcylation are involved in the etiology of metabolic diseases, cancers and neuropathologies.
30177911	9	9	gly	glycosylated	1589:1600	arg1	rhoptries					1541:1549	rhoptries	1541:1549	rhoptries	1541:1549	In a more original way, our proteomic analyses, confirmed by sWGA-enrichment and click-chemistry, revealed that rhoptries, proteins necessary for invasion, are glycosylated.
30177911	9	9	gly	glycosylated	1589:1600	arg1	proteins					1552:1559	proteins	1552:1559	proteins necessary for invasion	1552:1582	In a more original way, our proteomic analyses, confirmed by sWGA-enrichment and click-chemistry, revealed that rhoptries, proteins necessary for invasion, are glycosylated.
30177911	6	10	from	protists	1082:1089	arg1	variety					1031:1037	a wide variety	1024:1037	a wide variety of biological models but very few focus on protists	1024:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	10	from	protists	1082:1089	arg1	models					1053:1058	biological models	1042:1058	biological models	1042:1058	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	10	from	protists	1082:1089	arg1	focus					1073:1077	very few focus	1064:1077	very few focus on protists	1064:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	3	11	theme	diseases	592:599	arg1	etiology					570:577	the etiology	566:577	the etiology of metabolic diseases, cancers and neuropathologies	566:629	More and more evidences tend to show that deregulations in the homeostasis of O-GlcNAcylation are involved in the etiology of metabolic diseases, cancers and neuropathologies.
30177911	6	12	theme	models	1053:1058	arg1	variety					1031:1037	a wide variety	1024:1037	a wide variety of biological models but very few focus on protists	1024:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	12	theme	models	1053:1058	arg1	models					1053:1058	biological models	1042:1058	biological models	1042:1058	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	12	theme	models	1053:1058	arg1	focus					1073:1077	very few focus	1064:1077	very few focus on protists	1064:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	9	13	theme	necessary	1561:1569	arg1	rhoptries					1541:1549	rhoptries	1541:1549	rhoptries	1541:1549	In a more original way, our proteomic analyses, confirmed by sWGA-enrichment and click-chemistry, revealed that rhoptries, proteins necessary for invasion, are glycosylated.
30177911	9	13	theme	necessary	1561:1569	arg1	proteins					1552:1559	proteins	1552:1559	proteins necessary for invasion	1552:1582	In a more original way, our proteomic analyses, confirmed by sWGA-enrichment and click-chemistry, revealed that rhoptries, proteins necessary for invasion, are glycosylated.
30177911	1	14	theme	widespread	193:202	arg1	modification					223:234	a widespread post-translational modification	191:234	a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations	191:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	14	theme	widespread	193:202	arg1	O-GlcNAcylation					172:186	O-GlcNAcylation	172:186	O-GlcNAcylation	172:186	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	14	theme	widespread	193:202	arg1	β-N-acetylglucosaminylation					141:167	β-N-acetylglucosaminylation	141:167	β-N-acetylglucosaminylation	141:167	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	5	15	theme	OGT	808:810	arg1	form					800:803	A form	798:803	A form of OGT	798:810	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	1	16	theme	glycosylations	289:302	arg1	group					280:284	the large and heterogeneous group	252:284	the large and heterogeneous group of glycosylations	252:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	16	theme	glycosylations	289:302	arg1	glycosylations					289:302	glycosylations	289:302	glycosylations	289:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	17	theme	heterogeneous	266:278	arg1	group					280:284	the large and heterogeneous group	252:284	the large and heterogeneous group of glycosylations	252:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	17	theme	heterogeneous	266:278	arg1	glycosylations					289:302	glycosylations	289:302	glycosylations	289:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	7	18	from	enrichment	1121:1130	arg1	immunopurification					1150:1167	immunopurification	1150:1167	immunopurification	1150:1167	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	7	18	from	enrichment	1121:1130	arg1	sWGA-beads					1135:1144	sWGA-beads	1135:1144	sWGA-beads	1135:1144	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	1	19	theme	post-translational	204:221	arg1	modification					223:234	a widespread post-translational modification	191:234	a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations	191:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	19	theme	post-translational	204:221	arg1	O-GlcNAcylation					172:186	O-GlcNAcylation	172:186	O-GlcNAcylation	172:186	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	19	theme	post-translational	204:221	arg1	β-N-acetylglucosaminylation					141:167	β-N-acetylglucosaminylation	141:167	β-N-acetylglucosaminylation	141:167	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	5	20	theme	Toxoplasma	929:938	arg1	apicomplexans					915:927	the apicomplexans Toxoplasma gondii and Plasmodium falciparum	911:971	the apicomplexans Toxoplasma gondii and Plasmodium falciparum	911:971	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	5	20	theme	Toxoplasma	929:938	arg1	gondii					940:945	Toxoplasma gondii	929:945	Toxoplasma gondii	929:945	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	8	21	theme	proteins	1248:1255	arg1	Many					1236:1239	Many	1236:1239	Many	1236:1239	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	21	theme	proteins	1248:1255	arg1	proteins					1248:1255	the proteins	1244:1255	the proteins found to be O-GlcNAcylated	1244:1282	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	6	22	theme	biological	1042:1051	arg1	models					1053:1058	biological models	1042:1058	biological models	1042:1058	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	3	23	theme	neuropathologies	614:629	arg1	etiology					570:577	the etiology	566:577	the etiology of metabolic diseases, cancers and neuropathologies	566:629	More and more evidences tend to show that deregulations in the homeostasis of O-GlcNAcylation are involved in the etiology of metabolic diseases, cancers and neuropathologies.
30177911	6	24	theme	few	1069:1071	arg1	focus					1073:1077	very few focus	1064:1077	very few focus on protists	1064:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	4	25	theme	target	726:731	arg1	proteins					733:740	target proteins	726:740	target proteins confined within the cytosolic and nuclear compartments	726:795	O-GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments.
30177911	10	26	theme	specific	1666:1673	arg1	proteins					1648:1655	proteins	1648:1655	proteins strictly specific to organisms	1648:1686	Together, these data show that regardless of proteins strictly specific to organisms, O-GlcNAcylated proteins are rather similar among living beings.
30177911	6	27	from	variety	1031:1037	arg1	protists					1082:1089	protists	1082:1089	protists	1082:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	7	28	used	used	1116:1119	arg2	we					1113:1114	we	1113:1114	we	1113:1114	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	0	29	theme	O-GlcNAcome	119:129	arg1	Universality					99:110	the Universality	95:110	the Universality of the O-GlcNAcome	95:129	Apart From Rhoptries, Identification of Toxoplasma gondii's O-GlcNAcylated Proteins Reinforces the Universality of the O-GlcNAcome.
30177911	3	30	theme	cancers	602:608	arg1	etiology					570:577	the etiology	566:577	the etiology of metabolic diseases, cancers and neuropathologies	566:629	More and more evidences tend to show that deregulations in the homeostasis of O-GlcNAcylation are involved in the etiology of metabolic diseases, cancers and neuropathologies.
30177911	7	31	theme	Toxoplasma	1217:1226	arg1	gondii					1228:1233	Toxoplasma gondii	1217:1233	Toxoplasma gondii	1217:1233	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	6	32	theme	wide	1026:1029	arg1	variety					1031:1037	a wide variety	1024:1037	a wide variety of biological models but very few focus on protists	1024:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	32	theme	wide	1026:1029	arg1	models					1053:1058	biological models	1042:1058	biological models	1042:1058	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	32	theme	wide	1026:1029	arg1	focus					1073:1077	very few focus	1064:1077	very few focus on protists	1064:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	5	33	theme	O-GlcNAcylation	892:906	arg1	evidence					880:887	evidence	880:887	evidence of O-GlcNAcylation	880:906	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	4	34	theme	N-acetylglucosamine	693:711	arg1	residue					713:719	the N-acetylglucosamine residue	689:719	the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments	689:795	O-GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments.
30177911	8	35	theme	higher	1313:1318	arg1	eukaryotes					1320:1329	higher eukaryotes	1313:1329	higher eukaryotes	1313:1329	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	36	theme	shape	1355:1359	arg1	response					1375:1382	response	1375:1382	response to stress	1375:1392	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	36	theme	shape	1355:1359	arg1	organization					1361:1372	cell shape organization	1350:1372	cell shape organization	1350:1372	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	36	theme	shape	1355:1359	arg1	metabolism					1417:1426	metabolism	1417:1426	metabolism	1417:1426	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	36	theme	shape	1355:1359	arg1	synthesis					1403:1411	protein synthesis	1395:1411	protein synthesis	1395:1411	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	1	37	theme	large	256:260	arg1	group					280:284	the large and heterogeneous group	252:284	the large and heterogeneous group of glycosylations	252:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	37	theme	large	256:260	arg1	glycosylations					289:302	glycosylations	289:302	glycosylations	289:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	7	38	theme	O-GlcNAcylated	1190:1203	arg1	proteins					1205:1212	putative O-GlcNAcylated proteins	1181:1212	putative O-GlcNAcylated proteins in Toxoplasma gondii	1181:1233	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	1	39	link	O-linked	132:139	arg1	modification					223:234	a widespread post-translational modification	191:234	a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations	191:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	39	link	O-linked	132:139	arg1	O-GlcNAcylation					172:186	O-GlcNAcylation	172:186	O-GlcNAcylation	172:186	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	39	link	O-linked	132:139	arg1	β-N-acetylglucosaminylation					141:167	β-N-acetylglucosaminylation	141:167	β-N-acetylglucosaminylation	141:167	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	4	40	theme	nuclear	776:782	arg1	compartments					784:795	the cytosolic and nuclear compartments	758:795	the cytosolic and nuclear compartments	758:795	O-GlcNAc transferase or OGT is the enzyme that transfers the N-acetylglucosamine residue onto target proteins confined within the cytosolic and nuclear compartments.
30177911	0	41	theme	Toxoplasma	40:49	arg1	gondii					51:56	Toxoplasma gondii	40:56	Toxoplasma gondii's O-GlcNAcylated Proteins	40:82	Apart From Rhoptries, Identification of Toxoplasma gondii's O-GlcNAcylated Proteins Reinforces the Universality of the O-GlcNAcome.
30177911	9	42	theme	original	1439:1446	arg1	way					1448:1450	a more original way	1432:1450	a more original way	1432:1450	In a more original way, our proteomic analyses, confirmed by sWGA-enrichment and click-chemistry, revealed that rhoptries, proteins necessary for invasion, are glycosylated.
30177911	5	43	dep	apicomplexans	915:927	arg1	falciparum					962:971	Plasmodium falciparum	951:971	Plasmodium falciparum	951:971	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	5	43	dep	apicomplexans	915:927	arg1	apicomplexans					915:927	the apicomplexans Toxoplasma gondii and Plasmodium falciparum	911:971	the apicomplexans Toxoplasma gondii and Plasmodium falciparum	911:971	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	5	43	dep	apicomplexans	915:927	arg1	gondii					940:945	Toxoplasma gondii	929:945	Toxoplasma gondii	929:945	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	3	44	from	deregulations	498:510	arg1	homeostasis					519:529	the homeostasis	515:529	the homeostasis of O-GlcNAcylation	515:548	More and more evidences tend to show that deregulations in the homeostasis of O-GlcNAcylation are involved in the etiology of metabolic diseases, cancers and neuropathologies.
30177911	3	45	theme	O-GlcNAcylation	534:548	arg1	homeostasis					519:529	the homeostasis	515:529	the homeostasis of O-GlcNAcylation	515:548	More and more evidences tend to show that deregulations in the homeostasis of O-GlcNAcylation are involved in the etiology of metabolic diseases, cancers and neuropathologies.
30177911	1	46	theme	O-linked	132:139	arg1	modification					223:234	a widespread post-translational modification	191:234	a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations	191:302	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	46	theme	O-linked	132:139	arg1	O-GlcNAcylation					172:186	O-GlcNAcylation	172:186	O-GlcNAcylation	172:186	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	1	46	theme	O-linked	132:139	arg1	β-N-acetylglucosaminylation					141:167	β-N-acetylglucosaminylation	141:167	β-N-acetylglucosaminylation	141:167	O-linked β-N-acetylglucosaminylation or O-GlcNAcylation is a widespread post-translational modification that belongs to the large and heterogeneous group of glycosylations.
30177911	2	47	theme	transcription	384:396	arg1	regulation					370:379	regulation	370:379	regulation of transcription, replication, protein's fate, trafficking, and signaling	370:453	The functions managed by O-GlcNAcylation are diverse and include regulation of transcription, replication, protein's fate, trafficking, and signaling.
30177911	0	48	theme	O-GlcNAcylated	60:73	arg1	Proteins					75:82	Toxoplasma gondii's O-GlcNAcylated Proteins	40:82	Toxoplasma gondii's O-GlcNAcylated Proteins	40:82	Apart From Rhoptries, Identification of Toxoplasma gondii's O-GlcNAcylated Proteins Reinforces the Universality of the O-GlcNAcome.
30177911	8	49	theme	cell	1350:1353	arg1	response					1375:1382	response	1375:1382	response to stress	1375:1392	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	49	theme	cell	1350:1353	arg1	organization					1361:1372	cell shape organization	1350:1372	cell shape organization	1350:1372	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	49	theme	cell	1350:1353	arg1	metabolism					1417:1426	metabolism	1417:1426	metabolism	1417:1426	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	8	49	theme	cell	1350:1353	arg1	synthesis					1403:1411	protein synthesis	1395:1411	protein synthesis	1395:1411	Many of the proteins found to be O-GlcNAcylated were originally described in higher eukaryotes and participate in cell shape organization, response to stress, protein synthesis and metabolism.
30177911	9	50	theme	proteomic	1457:1465	arg1	analyses					1467:1474	our proteomic analyses	1453:1474	our proteomic analyses	1453:1474	In a more original way, our proteomic analyses, confirmed by sWGA-enrichment and click-chemistry, revealed that rhoptries, proteins necessary for invasion, are glycosylated.
30177911	10	51	theme	O-GlcNAcylated	1689:1702	arg1	proteins					1704:1711	O-GlcNAcylated proteins	1689:1711	O-GlcNAcylated proteins	1689:1711	Together, these data show that regardless of proteins strictly specific to organisms, O-GlcNAcylated proteins are rather similar among living beings.
30177911	7	52	from	proteins	1205:1212	arg1	gondii					1228:1233	Toxoplasma gondii	1217:1233	Toxoplasma gondii	1217:1233	In the present work, we used enrichment on sWGA-beads and immunopurification to identify putative O-GlcNAcylated proteins in Toxoplasma gondii.
30177911	5	53	theme	Plasmodium	951:960	arg1	falciparum					962:971	Plasmodium falciparum	951:971	Plasmodium falciparum	951:971	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	5	53	theme	Plasmodium	951:960	arg1	apicomplexans					915:927	the apicomplexans Toxoplasma gondii and Plasmodium falciparum	911:971	the apicomplexans Toxoplasma gondii and Plasmodium falciparum	911:971	A form of OGT was predicted for Toxoplasma and recently we were the first to show evidence of O-GlcNAcylation in the apicomplexans Toxoplasma gondii and Plasmodium falciparum.
30177911	6	54	theme	focus	1073:1077	arg1	variety					1031:1037	a wide variety	1024:1037	a wide variety of biological models but very few focus on protists	1024:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	54	theme	focus	1073:1077	arg1	models					1053:1058	biological models	1042:1058	biological models	1042:1058	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30177911	6	54	theme	focus	1073:1077	arg1	focus					1073:1077	very few focus	1064:1077	very few focus on protists	1064:1089	Numerous studies have explored the O-GlcNAcome in a wide variety of biological models but very few focus on protists.
30158774	8	0	theme	Formalin-fixed	1118:1131	arg1	blocks					1146:1151	Formalin-fixed paraffin wax blocks	1118:1151	Formalin-fixed paraffin wax blocks	1118:1151	Formalin-fixed paraffin wax blocks were prepared from the tissue samples obtained.
30158774	5	1	theme	MUC1	770:773	arg1	immunoexpression					775:790	the MUC1 immunoexpression	766:790	the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM)	766:858	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	3	2	theme	MUC1	541:544	arg1	expression					527:536	An aberrant expression	515:536	An aberrant expression of MUC1	515:544	An aberrant expression of MUC1 has been demonstrated in various human cancers.
30158774	1	3	theme	O-linked	178:185	arg1	content					200:206	a high O-linked carbohydrate content	171:206	a high O-linked carbohydrate content	171:206	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	8	4	theme	wax	1142:1144	arg1	blocks					1146:1151	Formalin-fixed paraffin wax blocks	1118:1151	Formalin-fixed paraffin wax blocks	1118:1151	Formalin-fixed paraffin wax blocks were prepared from the tissue samples obtained.
30158774	4	5	theme	lesions	673:679	arg1	region					706:711	head-and-neck region	692:711	neoplastic lesions other than head-and-neck region	662:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	4	5	theme	lesions	673:679	arg1	variety					651:657	a variety	649:657	a variety of neoplastic lesions other than head-and-neck region	649:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	4	5	theme	lesions	673:679	arg1	lesions					673:679	neoplastic lesions	662:679	neoplastic lesions other than head-and-neck region	662:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	15	6	theme	CONCLUSIONS	1844:1854	arg1	MUC1					1856:1859	CONCLUSIONS MUC1	1844:1859	CONCLUSIONS MUC1	1844:1859	CONCLUSIONS MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.
30158774	15	6	theme	CONCLUSIONS	1844:1854	arg1	biomarker					1875:1883	a reliable biomarker	1864:1883	a reliable biomarker for the diagnosis of OSCC	1864:1909	CONCLUSIONS MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.
30158774	1	7	link	O-linked	178:185	arg1	content					200:206	a high O-linked carbohydrate content	171:206	a high O-linked carbohydrate content	171:206	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	3	8	theme	human	579:583	arg1	cancers					585:591	various human cancers	571:591	various human cancers	571:591	An aberrant expression of MUC1 has been demonstrated in various human cancers.
30158774	6	9	theme	MUC1	931:934	arg1	immunoexpression					911:926	the immunoexpression	907:926	the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique	907:986	AIMS This study aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique.
30158774	7	10	theme	OSCC	1028:1031	arg1	patients					1016:1023	DESIGN Thirty patients	1002:1023	DESIGN Thirty patients	1002:1023	SETTINGS AND DESIGN Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM).
30158774	7	10	theme	OSCC	1028:1031	arg1	SETTINGS					989:996	SETTINGS	989:996	SETTINGS	989:996	SETTINGS AND DESIGN Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM).
30158774	8	11	theme	tissue	1176:1181	arg1	samples					1183:1189	the tissue samples	1172:1189	the tissue samples obtained	1172:1198	Formalin-fixed paraffin wax blocks were prepared from the tissue samples obtained.
30158774	12	12	theme	MUC1-positive	1535:1547	arg1	immunoreaction					1549:1562	MUC1-positive immunoreaction	1535:1562	MUC1-positive immunoreaction	1535:1562	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	1	13	theme	BACKGROUND	108:117	arg1	Mucins					119:124	BACKGROUND Mucins	108:124	BACKGROUND Mucins	108:124	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	1	13	theme	BACKGROUND	108:117	arg1	glycoproteins					152:164	high-molecular-weight glycoproteins	130:164	high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products	130:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	7	14	theme	DESIGN	1002:1007	arg1	patients					1016:1023	DESIGN Thirty patients	1002:1023	DESIGN Thirty patients	1002:1023	SETTINGS AND DESIGN Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM).
30158774	12	15	theme	OSCC	1517:1520	arg1	group					1528:1532	OSCC study group	1517:1532	OSCC study group	1517:1532	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	11	16	theme	P	1450:1450	arg1	<0.05					1452:1456	P <0.05	1450:1456	P <0.05	1450:1456	P <0.05 was considered to be statistically significant.
30158774	5	17	from	immunoexpression	775:790	arg1	NOM					855:857	NOM	855:857	NOM	855:857	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	17	from	immunoexpression	775:790	arg1	mucosa					847:852	normal oral mucosa	835:852	normal oral mucosa (NOM)	835:858	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	17	from	immunoexpression	775:790	arg1	OSCC					825:828	OSCC	825:828	OSCC	825:828	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	17	from	immunoexpression	775:790	arg1	carcinoma					814:822	oral squamous cell carcinoma	795:822	oral squamous cell carcinoma (OSCC)	795:829	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	14	18	theme	control	1793:1799	arg1	group					1801:1805	normal control group	1786:1805	normal control group	1786:1805	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	6	19	theme	immunohistochemical	958:976	arg1	technique					978:986	immunohistochemical technique	958:986	immunohistochemical technique	958:986	AIMS This study aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique.
30158774	4	20	theme	region	706:711	arg1	region					706:711	head-and-neck region	692:711	neoplastic lesions other than head-and-neck region	662:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	4	20	theme	region	706:711	arg1	variety					651:657	a variety	649:657	a variety of neoplastic lesions other than head-and-neck region	649:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	4	20	theme	region	706:711	arg1	lesions					673:679	neoplastic lesions	662:679	neoplastic lesions other than head-and-neck region	662:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	0	21	theme	oral	65:68	arg1	mucosa					70:75	normal oral mucosa	58:75	normal oral mucosa	58:75	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	0	22	from	Expression	0:9	arg1	mucosa					70:75	normal oral mucosa	58:75	normal oral mucosa	58:75	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	0	22	from	Expression	0:9	arg1	carcinoma					44:52	oral squamous cell carcinoma	25:52	oral squamous cell carcinoma	25:52	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	10	23	theme	ANALYSIS	1405:1412	arg1	test					1435:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test was used.
30158774	1	24	with	glycoproteins	152:164	arg1	content					200:206	a high O-linked carbohydrate content	171:206	a high O-linked carbohydrate content	171:206	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	12	25	theme	30	1602:1603	arg1	cases					1589:1593	21 (70%) cases	1580:1593	21 (70%) cases out of 30	1580:1603	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	12	25	theme	30	1602:1603	arg1	%					1586:1586	70%	1584:1586	70%	1584:1586	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	0	26	theme	immunohistochemical	81:99	arg1	study					101:105	An immunohistochemical study	78:105	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.	0:106	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	4	27	dep	other	681:685	arg1	than					687:690	than	687:690	than	687:690	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	2	28	theme	cellular	449:456	arg1	signaling					504:512	signaling	504:512	signaling	504:512	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	2	28	theme	cellular	449:456	arg1	differentiation					484:498	differentiation	484:498	differentiation	484:498	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	2	28	theme	cellular	449:456	arg1	functions					458:466	various cellular functions	441:466	various cellular functions such as growth, differentiation and signaling	441:512	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	2	28	theme	cellular	449:456	arg1	growth					476:481	growth	476:481	growth	476:481	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	14	29	from	expression	1704:1713	arg1	group					1731:1735	OSCC group	1726:1735	OSCC group	1726:1735	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	5	30	theme	squamous	800:807	arg1	OSCC					825:828	OSCC	825:828	OSCC	825:828	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	30	theme	squamous	800:807	arg1	carcinoma					814:822	oral squamous cell carcinoma	795:822	oral squamous cell carcinoma (OSCC)	795:829	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	1	31	theme	secreted	291:298	arg1	products					300:307	membrane-bound and/or secreted products	269:307	membrane-bound and/or secreted products	269:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	0	32	theme	mucin-1	14:20	arg1	Expression					0:9	Expression	0:9	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.	0:106	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	15	33	theme	further	1916:1922	arg1	studies					1924:1930	further studies	1916:1930	further studies	1916:1930	CONCLUSIONS MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.
30158774	12	34	dep	RESULTS	1506:1512	arg1	observed					1568:1575	observed	1568:1575	was observed in 21 (70%) cases out of 30	1564:1603	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	2	35	theme	body	413:416	arg1	membranes					390:398	the mucous membranes	379:398	the mucous membranes of the human body	379:416	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	5	36	theme	normal	835:840	arg1	NOM					855:857	NOM	855:857	NOM	855:857	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	36	theme	normal	835:840	arg1	mucosa					847:852	normal oral mucosa	835:852	normal oral mucosa (NOM)	835:858	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	9	37	theme	positive	1304:1311	arg1	cells					1313:1317	positive cells	1304:1317	positive cells along with distribution and localization of immunoexpression	1304:1378	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	0	38	theme	oral	25:28	arg1	carcinoma					44:52	oral squamous cell carcinoma	25:52	oral squamous cell carcinoma	25:52	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	0	39	theme	cell	39:42	arg1	carcinoma					44:52	oral squamous cell carcinoma	25:52	oral squamous cell carcinoma	25:52	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	14	40	theme	OSCC	1726:1729	arg1	group					1731:1735	OSCC group	1726:1735	OSCC group	1726:1735	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	2	41	theme	transmembrane	330:342	arg1	mucin					344:348	a transmembrane mucin	328:348	a transmembrane mucin that protects and lubricates the mucous membranes of the human body	328:416	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	2	41	theme	transmembrane	330:342	arg1	Mucin-1					310:316	Mucin-1	310:316	Mucin-1 (MUC1)	310:323	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	14	42	theme	MUC1	1718:1721	arg1	expression					1704:1713	The immunohistochemical expression	1680:1713	The immunohistochemical expression of MUC1 in OSCC group	1680:1735	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	14	42	theme	MUC1	1718:1721	arg1	significant					1755:1765	significant	1755:1765	significant	1755:1765	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	3	43	theme	aberrant	518:525	arg1	expression					527:536	An aberrant expression	515:536	An aberrant expression of MUC1	515:544	An aberrant expression of MUC1 has been demonstrated in various human cancers.
30158774	5	44	theme	oral	842:845	arg1	NOM					855:857	NOM	855:857	NOM	855:857	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	44	theme	oral	842:845	arg1	mucosa					847:852	normal oral mucosa	835:852	normal oral mucosa (NOM)	835:858	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	1	45	theme	secretory	239:247	arg1	cells					260:264	many secretory epithelial cells	234:264	many secretory epithelial cells as membrane-bound and/or secreted products	234:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	0	46	dep	Expression	0:9	arg1	study					101:105	An immunohistochemical study	78:105	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.	0:106	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	9	47	theme	immunoexpression	1363:1378	arg1	localization					1347:1358	localization	1347:1358	localization	1347:1358	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	9	47	theme	immunoexpression	1363:1378	arg1	distribution					1330:1341	distribution	1330:1341	distribution	1330:1341	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	1	48	theme	membrane-bound	269:282	arg1	products					300:307	membrane-bound and/or secreted products	269:307	membrane-bound and/or secreted products	269:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	4	49	theme	Many	594:597	arg1	studies					599:605	Many studies	594:605	Many studies on MUC1 expression	594:624	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	1	50	theme	high	173:176	arg1	content					200:206	a high O-linked carbohydrate content	171:206	a high O-linked carbohydrate content	171:206	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	7	51	theme	control	1097:1103	arg1	group					1105:1109	the control group	1093:1109	the control group (NOM)	1093:1115	SETTINGS AND DESIGN Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM).
30158774	7	51	theme	control	1097:1103	arg1	NOM					1112:1114	NOM	1112:1114	NOM	1112:1114	SETTINGS AND DESIGN Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM).
30158774	7	52	theme	study	1044:1048	arg1	group					1050:1054	the study group	1040:1054	the study group	1040:1054	SETTINGS AND DESIGN Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM).
30158774	3	53	theme	various	571:577	arg1	cancers					585:591	various human cancers	571:591	various human cancers	571:591	An aberrant expression of MUC1 has been demonstrated in various human cancers.
30158774	1	54	theme	carbohydrate	187:198	arg1	content					200:206	a high O-linked carbohydrate content	171:206	a high O-linked carbohydrate content	171:206	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	8	55	theme	paraffin	1133:1140	arg1	blocks					1146:1151	Formalin-fixed paraffin wax blocks	1118:1151	Formalin-fixed paraffin wax blocks	1118:1151	Formalin-fixed paraffin wax blocks were prepared from the tissue samples obtained.
30158774	4	56	theme	neoplastic	662:671	arg1	lesions					673:679	neoplastic lesions	662:679	neoplastic lesions other than head-and-neck region	662:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	10	57	theme	Chi-square	1424:1433	arg1	test					1435:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test was used.
30158774	13	58	theme	MUC1	1657:1660	arg1	immunoexpression					1662:1677	MUC1 immunoexpression	1657:1677	MUC1 immunoexpression	1657:1677	All the samples in control group were negative for MUC1 immunoexpression.
30158774	1	59	gly	glycoproteins	152:164	arg1	Mucins					119:124	BACKGROUND Mucins	108:124	BACKGROUND Mucins	108:124	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	1	59	gly	glycoproteins	152:164	arg1	glycoproteins					152:164	high-molecular-weight glycoproteins	130:164	high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products	130:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	9	60	theme	MATERIALS	1201:1209	arg1	IHC					1245:1247	IHC	1245:1247	IHC	1245:1247	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	9	60	theme	MATERIALS	1201:1209	arg1	Immunohistochemistry					1223:1242	MATERIALS AND METHODS Immunohistochemistry	1201:1242	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1	1201:1257	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	9	61	theme	METHODS	1215:1221	arg1	IHC					1245:1247	IHC	1245:1247	IHC	1245:1247	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	9	61	theme	METHODS	1215:1221	arg1	Immunohistochemistry					1223:1242	MATERIALS AND METHODS Immunohistochemistry	1201:1242	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1	1201:1257	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	12	62	theme	study	1522:1526	arg1	group					1528:1532	OSCC study group	1517:1532	OSCC study group	1517:1532	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	0	63	theme	normal	58:63	arg1	mucosa					70:75	normal oral mucosa	58:75	normal oral mucosa	58:75	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	1	64	theme	high-molecular-weight	130:150	arg1	Mucins					119:124	BACKGROUND Mucins	108:124	BACKGROUND Mucins	108:124	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	1	64	theme	high-molecular-weight	130:150	arg1	glycoproteins					152:164	high-molecular-weight glycoproteins	130:164	high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products	130:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	9	65	theme	distribution	1330:1341	arg1	percentage					1290:1299	the overall percentage	1278:1299	the overall percentage of positive cells along with distribution and localization of immunoexpression	1278:1378	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	12	66	located	observed	1568:1575	arg1	cases					1589:1593	21 (70%) cases	1580:1593	21 (70%) cases out of 30	1580:1603	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	12	66	located	observed	1568:1575	arg1	%					1586:1586	70%	1584:1586	70%	1584:1586	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	12	66	located	observed	1568:1575	arg1	group					1528:1532	OSCC study group	1517:1532	OSCC study group	1517:1532	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	12	66	located	observed	1568:1575	arg2	immunoreaction					1549:1562	MUC1-positive immunoreaction	1535:1562	MUC1-positive immunoreaction	1535:1562	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	14	67	theme	normal	1786:1791	arg1	group					1801:1805	normal control group	1786:1805	normal control group	1786:1805	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	10	68	used	used	1444:1447	arg2	test					1435:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test was used.
30158774	4	69	theme	head-and-neck	692:704	arg1	region					706:711	head-and-neck region	692:711	neoplastic lesions other than head-and-neck region	662:711	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	4	70	from	studies	599:605	arg1	expression					615:624	MUC1 expression	610:624	MUC1 expression	610:624	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	9	71	dep	along	1319:1323	arg1	with					1325:1328	with	1325:1328	with	1325:1328	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	10	72	theme	STATISTICAL	1393:1403	arg1	test					1435:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test	1393:1438	STATISTICAL ANALYSIS Pearson's Chi-square test was used.
30158774	15	73	theme	reliable	1866:1873	arg1	MUC1					1856:1859	CONCLUSIONS MUC1	1844:1859	CONCLUSIONS MUC1	1844:1859	CONCLUSIONS MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.
30158774	15	73	theme	reliable	1866:1873	arg1	biomarker					1875:1883	a reliable biomarker	1864:1883	a reliable biomarker for the diagnosis of OSCC	1864:1909	CONCLUSIONS MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.
30158774	5	74	theme	oral	795:798	arg1	OSCC					825:828	OSCC	825:828	OSCC	825:828	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	74	theme	oral	795:798	arg1	carcinoma					814:822	oral squamous cell carcinoma	795:822	oral squamous cell carcinoma (OSCC)	795:829	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	2	75	theme	various	441:447	arg1	signaling					504:512	signaling	504:512	signaling	504:512	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	2	75	theme	various	441:447	arg1	differentiation					484:498	differentiation	484:498	differentiation	484:498	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	2	75	theme	various	441:447	arg1	functions					458:466	various cellular functions	441:466	various cellular functions such as growth, differentiation and signaling	441:512	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	2	75	theme	various	441:447	arg1	growth					476:481	growth	476:481	growth	476:481	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	13	76	theme	control	1625:1631	arg1	group					1633:1637	control group	1625:1637	control group	1625:1637	All the samples in control group were negative for MUC1 immunoexpression.
30158774	2	77	theme	mucous	383:388	arg1	membranes					390:398	the mucous membranes	379:398	the mucous membranes of the human body	379:416	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	5	78	theme	cell	809:812	arg1	OSCC					825:828	OSCC	825:828	OSCC	825:828	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	5	78	theme	cell	809:812	arg1	carcinoma					814:822	oral squamous cell carcinoma	795:822	oral squamous cell carcinoma (OSCC)	795:829	In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM).
30158774	9	79	theme	overall	1282:1288	arg1	percentage					1290:1299	the overall percentage	1278:1299	the overall percentage of positive cells along with distribution and localization of immunoexpression	1278:1378	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	6	80	from	immunoexpression	911:926	arg1	OSCC					947:950	OSCC	947:950	OSCC	947:950	AIMS This study aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique.
30158774	6	80	from	immunoexpression	911:926	arg1	NOM					939:941	NOM	939:941	NOM	939:941	AIMS This study aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique.
30158774	0	81	theme	squamous	30:37	arg1	carcinoma					44:52	oral squamous cell carcinoma	25:52	oral squamous cell carcinoma	25:52	Expression of mucin-1 in oral squamous cell carcinoma and normal oral mucosa: An immunohistochemical study.
30158774	13	82	from	samples	1614:1620	arg1	group					1633:1637	control group	1625:1637	control group	1625:1637	All the samples in control group were negative for MUC1 immunoexpression.
30158774	2	83	theme	human	407:411	arg1	body					413:416	the human body	403:416	the human body	403:416	Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling.
30158774	9	84	theme	cells	1313:1317	arg1	percentage					1290:1299	the overall percentage	1278:1299	the overall percentage of positive cells along with distribution and localization of immunoexpression	1278:1378	MATERIALS AND METHODS Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied.
30158774	4	85	theme	MUC1	610:613	arg1	expression					615:624	MUC1 expression	610:624	MUC1 expression	610:624	Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region.
30158774	15	86	theme	OSCC	1906:1909	arg1	diagnosis					1893:1901	the diagnosis	1889:1901	the diagnosis of OSCC	1889:1909	CONCLUSIONS MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.
30158774	1	87	theme	many	234:237	arg1	cells					260:264	many secretory epithelial cells	234:264	many secretory epithelial cells as membrane-bound and/or secreted products	234:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
30158774	15	88	from	role	1958:1961	arg1	prognosis					1966:1974	prognosis	1966:1974	prognosis	1966:1974	CONCLUSIONS MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis.
30158774	6	89	dep	AIMS	861:864	arg1	aims					877:880	aims	877:880	aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique	877:986	AIMS This study aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique.
30158774	14	90	theme	immunohistochemical	1684:1702	arg1	expression					1704:1713	The immunohistochemical expression	1680:1713	The immunohistochemical expression of MUC1 in OSCC group	1680:1735	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	14	90	theme	immunohistochemical	1684:1702	arg1	significant					1755:1765	significant	1755:1765	significant	1755:1765	The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square).
30158774	12	91	dep	30	1602:1603	arg1	out					1595:1597	out	1595:1597	out	1595:1597	RESULTS In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30.
30158774	1	92	theme	epithelial	249:258	arg1	cells					260:264	many secretory epithelial cells	234:264	many secretory epithelial cells as membrane-bound and/or secreted products	234:307	BACKGROUND Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products.
29236108	7	0	theme	pincer	1237:1242	arg1	complexes					1244:1252	All newly synthesized pincer complexes	1215:1252	All newly synthesized pincer complexes	1215:1252	All newly synthesized pincer complexes were employed to test their catalytic activities in Mizoroki-Heck reactions.
29236108	2	1	with	salts	390:394	arg1	moieties					422:429	pyridine moieties	413:429	pyridine moieties surviving from the alkylations	413:460	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	1	2	theme	pyridine-bridged	179:194	arg1	C/D					225:227	C/D	225:227	C/D	225:227	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	1	2	theme	pyridine-bridged	179:194	arg1	A/B					217:219	A/B	217:219	A/B	217:219	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	1	2	theme	pyridine-bridged	179:194	arg1	1,2,3-triazoles					200:214	Four pyridine-bridged bis(1,2,3-triazoles)	174:215	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D	174:227	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	1	3	theme	"	257:257	arg1	reactions					259:267	"click" reactions	251:267	"click" reactions	251:267	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	8	4	theme	substrate	1527:1535	arg1	scope					1537:1541	the catalyst variation or substrate scope	1501:1541	scope	1537:1541	Positive mercury drop tests implied that the pincer-type complexes do not survive under the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope.
29236108	3	5	theme	pyridine	699:706	arg1	by-products					725:735	by-products	725:735	by-products	725:735	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	3	5	theme	pyridine	699:706	arg1	thioaldehydes					708:720	pyridine thioaldehydes	699:720	pyridine thioaldehydes	699:720	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	1	6	theme	bis	196:198	arg1	C/D					225:227	C/D	225:227	C/D	225:227	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	1	6	theme	bis	196:198	arg1	A/B					217:219	A/B	217:219	A/B	217:219	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	1	6	theme	bis	196:198	arg1	1,2,3-triazoles					200:214	Four pyridine-bridged bis(1,2,3-triazoles)	174:215	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D	174:227	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	2	7	dep	salts	390:394	arg1	3/4					404:406	3/4	404:406	3/4	404:406	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	2	7	dep	salts	390:394	arg1	1/2					396:398	1/2	396:398	1/2	396:398	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	5	8	with	protocol	904:911	arg1	salt					918:921	salt 3	918:923	salt 3	918:923	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	2	9	theme	C/D	306:308	arg1	Methylations/ethylations					270:293	Methylations/ethylations	270:293	Methylations/ethylations of A/B and C/D employing Meerwein's salts	270:335	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	5	10	theme	-type	952:956	arg1	complex					975:981	the [CNC]-type palladium pincer complex 8	943:983	the [CNC]-type palladium pincer complex 8	943:983	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	7	11	theme	synthesized	1225:1235	arg1	complexes					1244:1252	All newly synthesized pincer complexes	1215:1252	All newly synthesized pincer complexes	1215:1252	All newly synthesized pincer complexes were employed to test their catalytic activities in Mizoroki-Heck reactions.
29236108	5	12	theme	pincer	968:973	arg1	complex					975:981	the [CNC]-type palladium pincer complex 8	943:983	the [CNC]-type palladium pincer complex 8	943:983	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	3	13	theme	salts	506:510	arg1	reactions					482:490	the reactions	478:490	the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur	478:561	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	8	14	theme	mercury	1340:1346	arg1	tests					1353:1357	Positive mercury drop tests	1331:1357	Positive mercury drop tests	1331:1357	Positive mercury drop tests implied that the pincer-type complexes do not survive under the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope.
29236108	7	15	theme	Mizoroki-Heck	1306:1318	arg1	reactions					1320:1328	Mizoroki-Heck reactions	1306:1328	Mizoroki-Heck reactions	1306:1328	All newly synthesized pincer complexes were employed to test their catalytic activities in Mizoroki-Heck reactions.
29236108	3	16	from	K2CO3	521:525	arg1	presence					534:541	the presence	530:541	the presence of elemental sulfur	530:561	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	2	17	theme	A/B	298:300	arg1	Methylations/ethylations					270:293	Methylations/ethylations	270:293	Methylations/ethylations of A/B and C/D employing Meerwein's salts	270:335	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	4	18	dep	reactions	792:800	arg1	synthesize					805:814	synthesize	805:814	to synthesize carbene-sulfur zwitterions 9/10	802:846	In contrast, in the case of "C-linked" salts 3/4, the reactions to synthesize carbene-sulfur zwitterions 9/10 proceeded smoothly.
29236108	7	19	from	activities	1292:1301	arg1	reactions					1320:1328	Mizoroki-Heck reactions	1306:1328	Mizoroki-Heck reactions	1306:1328	All newly synthesized pincer complexes were employed to test their catalytic activities in Mizoroki-Heck reactions.
29236108	4	20	theme	"	775:775	arg1	salts					777:781	"C-linked" salts 3/4	766:785	"C-linked" salts 3/4	766:785	In contrast, in the case of "C-linked" salts 3/4, the reactions to synthesize carbene-sulfur zwitterions 9/10 proceeded smoothly.
29236108	8	21	theme	catalysis	1437:1445	arg1	conditions					1423:1432	the conditions	1419:1432	the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope	1419:1541	Positive mercury drop tests implied that the pincer-type complexes do not survive under the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope.
29236108	0	22	theme	pincer-type	10:20	arg1	complexes					22:30	Palladium pincer-type complexes	0:30	Palladium pincer-type complexes	0:30	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	5	23	theme	silver-carbene	880:893	arg1	protocol					904:911	a silver-carbene transfer protocol	878:911	a silver-carbene transfer protocol with salt 3	878:923	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	5	23	theme	silver-carbene	880:893	arg1	precursor					932:940	the precursor	928:940	the precursor	928:940	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	0	24	theme	Palladium	0:8	arg1	complexes					22:30	Palladium pincer-type complexes	0:30	Palladium pincer-type complexes	0:30	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	4	25	theme	C-linked	767:774	arg1	salts					777:781	"C-linked" salts 3/4	766:785	"C-linked" salts 3/4	766:785	In contrast, in the case of "C-linked" salts 3/4, the reactions to synthesize carbene-sulfur zwitterions 9/10 proceeded smoothly.
29236108	2	26	theme	salts	390:394	arg1	formation					348:356	the formation	344:356	the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations	344:460	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	8	27	theme	drop	1348:1351	arg1	tests					1353:1357	Positive mercury drop tests	1331:1357	Positive mercury drop tests	1331:1357	Positive mercury drop tests implied that the pincer-type complexes do not survive under the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope.
29236108	4	28	theme	carbene-sulfur	816:829	arg1	9/10					843:846	carbene-sulfur zwitterions 9/10	816:846	carbene-sulfur zwitterions 9/10	816:846	In contrast, in the case of "C-linked" salts 3/4, the reactions to synthesize carbene-sulfur zwitterions 9/10 proceeded smoothly.
29236108	3	29	theme	elemental	546:554	arg1	sulfur					556:561	elemental sulfur	546:561	elemental sulfur	546:561	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	5	30	theme	solid-state	1006:1016	arg1	structure					1018:1026	the solid-state structure	1002:1026	the solid-state structure of which was determined by X-ray diffraction analysis	1002:1080	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	5	31	theme	palladium	958:966	arg1	complex					975:981	the [CNC]-type palladium pincer complex 8	943:983	the [CNC]-type palladium pincer complex 8	943:983	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	4	32	theme	salts	777:781	arg1	case					758:761	the case	754:761	the case of "C-linked" salts 3/4	754:785	In contrast, in the case of "C-linked" salts 3/4, the reactions to synthesize carbene-sulfur zwitterions 9/10 proceeded smoothly.
29236108	5	33	theme	diffraction	1061:1071	arg1	analysis					1073:1080	X-ray diffraction analysis	1055:1080	X-ray diffraction analysis	1055:1080	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	3	34	theme	sulfur	556:561	arg1	presence					534:541	the presence	530:541	the presence of elemental sulfur	530:561	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	0	35	theme	sulfur	49:54	arg1	adducts					56:62	zwitterionic sulfur adducts	36:62	zwitterionic sulfur adducts	36:62	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	3	36	theme	mesoionic	581:589	arg1	adducts					614:620	the mesoionic carbene-sulfur betaine adducts	577:620	the mesoionic carbene-sulfur betaine adducts	577:620	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	5	37	theme	transfer	895:902	arg1	protocol					904:911	a silver-carbene transfer protocol	878:911	a silver-carbene transfer protocol with salt 3	878:923	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	5	37	theme	transfer	895:902	arg1	precursor					932:940	the precursor	928:940	the precursor	928:940	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	2	38	theme	pyridine	413:420	arg1	moieties					422:429	pyridine moieties	413:429	pyridine moieties surviving from the alkylations	413:460	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	0	39	theme	zwitterionic	36:47	arg1	adducts					56:62	zwitterionic sulfur adducts	36:62	zwitterionic sulfur adducts	36:62	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	0	40	theme	catalytic	150:158	arg1	applications					160:171	catalytic applications	150:171	catalytic applications	150:171	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	3	41	theme	carbene-sulfur	591:604	arg1	adducts					614:620	the mesoionic carbene-sulfur betaine adducts	577:620	the mesoionic carbene-sulfur betaine adducts	577:620	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	8	42	theme	Positive	1331:1338	arg1	tests					1353:1357	Positive mercury drop tests	1331:1357	Positive mercury drop tests	1331:1357	Positive mercury drop tests implied that the pincer-type complexes do not survive under the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope.
29236108	3	43	theme	1,5-disubstituted	648:664	arg1	triazoles					666:674	1,5-disubstituted triazoles	648:674	1,5-disubstituted triazoles	648:674	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	4	44	theme	zwitterions	831:841	arg1	9/10					843:846	carbene-sulfur zwitterions 9/10	816:846	carbene-sulfur zwitterions 9/10	816:846	In contrast, in the case of "C-linked" salts 3/4, the reactions to synthesize carbene-sulfur zwitterions 9/10 proceeded smoothly.
29236108	3	45	theme	N-linked	496:503	arg1	salts					506:510	"N-linked" salts 1/2	495:514	"N-linked" salts 1/2	495:514	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	3	46	with	reactions	482:490	arg1	K2CO3					521:525	K2CO3	521:525	K2CO3 in the presence of elemental sulfur	521:561	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	8	47	theme	catalyst	1505:1512	arg1	variation					1514:1522	the catalyst variation or substrate scope	1501:1541	variation	1514:1522	Positive mercury drop tests implied that the pincer-type complexes do not survive under the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope.
29236108	1	48	dep	1,2,3-triazoles	200:214	arg1	C/D					225:227	C/D	225:227	C/D	225:227	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	1	48	dep	1,2,3-triazoles	200:214	arg1	A/B					217:219	A/B	217:219	A/B	217:219	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	1	48	dep	1,2,3-triazoles	200:214	arg1	1,2,3-triazoles					200:214	Four pyridine-bridged bis(1,2,3-triazoles)	174:215	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D	174:227	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29236108	3	49	theme	"	504:504	arg1	salts					506:510	"N-linked" salts 1/2	495:514	"N-linked" salts 1/2	495:514	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	7	50	theme	catalytic	1282:1290	arg1	activities					1292:1301	their catalytic activities	1276:1301	their catalytic activities in Mizoroki-Heck reactions	1276:1328	All newly synthesized pincer complexes were employed to test their catalytic activities in Mizoroki-Heck reactions.
29236108	3	51	link	N-linked	496:503	arg1	salts					506:510	"N-linked" salts 1/2	495:514	"N-linked" salts 1/2	495:514	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	4	52	link	C-linked	767:774	arg1	salts					777:781	"C-linked" salts 3/4	766:785	"C-linked" salts 3/4	766:785	In contrast, in the case of "C-linked" salts 3/4, the reactions to synthesize carbene-sulfur zwitterions 9/10 proceeded smoothly.
29236108	6	53	theme	acetato	1163:1169	arg1	complex					1171:1177	acetato complex 11	1163:1180	acetato complex 11	1163:1180	Complex 8 underwent ligand substitutions with silver carboxylates producing the acetato complex 11 and trifluoroacetato complex 12.
29236108	3	54	dep	afforded	639:646	arg1	produce					691:697	produce	691:697	may produce pyridine thioaldehydes as by-products	687:735	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	0	55	dep	complexes	22:30	arg1	characterizations					128:144	characterizations	128:144	characterizations	128:144	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	0	55	dep	complexes	22:30	arg1	applications					160:171	catalytic applications	150:171	catalytic applications	150:171	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	0	55	dep	complexes	22:30	arg1	syntheses					117:125	syntheses	117:125	syntheses	117:125	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	6	56	theme	ligand	1103:1108	arg1	substitutions					1110:1122	ligand substitutions	1103:1122	ligand substitutions	1103:1122	Complex 8 underwent ligand substitutions with silver carboxylates producing the acetato complex 11 and trifluoroacetato complex 12.
29236108	8	57	theme	pincer-type	1376:1386	arg1	complexes					1388:1396	the pincer-type complexes	1372:1396	the pincer-type complexes	1372:1396	Positive mercury drop tests implied that the pincer-type complexes do not survive under the conditions of catalysis, owing to which no conclusions can be drawn regarding the catalyst variation or substrate scope.
29236108	6	58	theme	silver	1129:1134	arg1	carboxylates					1136:1147	silver carboxylates	1129:1147	silver carboxylates producing the acetato complex 11 and trifluoroacetato complex 12	1129:1212	Complex 8 underwent ligand substitutions with silver carboxylates producing the acetato complex 11 and trifluoroacetato complex 12.
29236108	0	59	theme	bis	84:86	arg1	complexes					22:30	Palladium pincer-type complexes	0:30	Palladium pincer-type complexes	0:30	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	0	59	theme	bis	84:86	arg1	adducts					56:62	zwitterionic sulfur adducts	36:62	zwitterionic sulfur adducts	36:62	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	5	60	theme	X-ray	1055:1059	arg1	analysis					1073:1080	X-ray diffraction analysis	1055:1080	X-ray diffraction analysis	1055:1080	Employing a silver-carbene transfer protocol with salt 3 as the precursor, the [CNC]-type palladium pincer complex 8 was synthesized, the solid-state structure of which was determined by X-ray diffraction analysis.
29236108	3	61	theme	betaine	606:612	arg1	adducts					614:620	the mesoionic carbene-sulfur betaine adducts	577:620	the mesoionic carbene-sulfur betaine adducts	577:620	Interestingly, the reactions of "N-linked" salts 1/2 with K2CO3 in the presence of elemental sulfur did not yield the mesoionic carbene-sulfur betaine adducts but unexpectedly afforded 1,5-disubstituted triazoles 5/6, which may produce pyridine thioaldehydes as by-products.
29236108	2	62	theme	dicationic	379:388	arg1	salts					390:394	the corresponding dicationic salts 1/2 and 3/4	361:406	the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations	361:460	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	6	63	theme	trifluoroacetato	1186:1201	arg1	complex					1203:1209	trifluoroacetato complex 12	1186:1212	trifluoroacetato complex 12	1186:1212	Complex 8 underwent ligand substitutions with silver carboxylates producing the acetato complex 11 and trifluoroacetato complex 12.
29236108	0	64	theme	pyridine-bridged	67:82	arg1	1,2,3-triazolin-5-ylidenes					88:113	1,2,3-triazolin-5-ylidenes	88:113	1,2,3-triazolin-5-ylidenes	88:113	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	0	64	theme	pyridine-bridged	67:82	arg1	bis					84:86	pyridine-bridged bis	67:86	pyridine-bridged bis(1,2,3-triazolin-5-ylidenes)	67:114	Palladium pincer-type complexes and zwitterionic sulfur adducts of pyridine-bridged bis(1,2,3-triazolin-5-ylidenes): syntheses, characterizations and catalytic applications.
29236108	2	65	theme	corresponding	365:377	arg1	salts					390:394	the corresponding dicationic salts 1/2 and 3/4	361:406	the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations	361:460	Methylations/ethylations of A/B and C/D employing Meerwein's salts led to the formation of the corresponding dicationic salts 1/2 and 3/4 with pyridine moieties surviving from the alkylations.
29236108	1	66	theme	click	252:256	arg1	reactions					259:267	"click" reactions	251:267	"click" reactions	251:267	Four pyridine-bridged bis(1,2,3-triazoles) A/B and C/D have been prepared by "click" reactions.
29499461	2	0	theme	product	547:553	arg1	efficacy					531:538	efficacy	531:538	efficacy	531:538	In addition, alteration in glycosylation may influence the safety and efficacy of the product.
29499461	2	0	theme	product	547:553	arg1	safety					520:525	safety	520:525	safety	520:525	In addition, alteration in glycosylation may influence the safety and efficacy of the product.
29499461	2	1	from	alteration	474:483	arg1	glycosylation					488:500	glycosylation	488:500	glycosylation	488:500	In addition, alteration in glycosylation may influence the safety and efficacy of the product.
29499461	1	2	theme	carbohydrate	157:168	arg1	moieties					170:177	The carbohydrate moieties	153:177	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars	153:268	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	6	3	dep	sialylated	1253:1262	arg1	galactosylated					1283:1296	galactosylated	1283:1296	galactosylated	1283:1296	Differences in sialylated, core fucosylated, galactosylated and high mannose glycans were all quantified.
29499461	6	3	dep	sialylated	1253:1262	arg1	fucosylated					1270:1280	fucosylated	1270:1280	fucosylated	1270:1280	Differences in sialylated, core fucosylated, galactosylated and high mannose glycans were all quantified.
29499461	0	4	theme	N-glycosylation	80:94	arg1	version					130:136	a biosimilar version	117:136	a biosimilar version of etanercept	117:150	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	0	4	theme	N-glycosylation	80:94	arg1	comparison					62:71	Quantitative comparison	49:71	Quantitative comparison of the N-glycosylation of the innovator	49:111	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	1	5	theme	complement-dependent	377:396	arg1	cytotoxicity					398:409	complement-dependent cytotoxicity	377:409	complement-dependent cytotoxicity	377:409	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	4	6	theme	such	768:771	arg1	biopharmaceuticals					773:790	such biopharmaceuticals	768:790	such biopharmaceuticals (both innovator and biosimilar products)	768:831	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	4	6	theme	such	768:771	arg1	products					823:830	both innovator and biosimilar products	793:830	both innovator and biosimilar products	793:830	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	1	7	theme	essential	275:283	arg1	roles					285:289	essential roles	275:289	essential roles	275:289	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	0	8	theme	innovator	103:111	arg1	N-glycosylation					80:94	the N-glycosylation	76:94	the N-glycosylation of the innovator	76:111	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	5	9	theme	carbohydrate	1215:1226	arg1	profiles					1228:1235	their N-linked carbohydrate profiles	1200:1235	their N-linked carbohydrate profiles	1200:1235	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	1	10	from	moieties	170:177	arg1	chains					198:203	the polypeptide chains	182:203	the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars	182:268	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	5	11	theme	biosimilarity	1044:1056	arg1	version					1130:1136	a biosimilar version	1117:1136	a biosimilar version of etanercept	1117:1150	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	11	theme	biosimilarity	1044:1056	arg1	aspect					1034:1039	the glycosylation aspect	1016:1039	the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator	1016:1111	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	12	theme	glycosylation	1020:1032	arg1	aspect					1034:1039	the glycosylation aspect	1016:1039	the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator	1016:1111	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	4	13	theme	biopharmaceuticals	773:790	arg1	moieties					756:763	the carbohydrate moieties	739:763	the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products)	739:831	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	1	14	theme	anti-inflammatory	412:428	arg1	functions					430:438	anti-inflammatory functions	412:438	anti-inflammatory functions	412:438	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	3	15	gly	glycoprotein	651:662	arg1	glycoprotein					651:662	glycoprotein biotherapeutics	651:678	glycoprotein biotherapeutics	651:678	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	0	16	gly	N-glycosylation	80:94	arg1	innovator					103:111	the innovator	99:111	the innovator	99:111	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	4	17	theme	carbohydrate	743:754	arg1	moieties					756:763	the carbohydrate moieties	739:763	the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products)	739:831	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	7	18	theme	serum	1520:1524	arg1	half-life					1526:1534	serum half-life	1520:1534	serum half-life	1520:1534	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	5	19	theme	rapid	940:944	arg1	Benepali®					1165:1173	Benepali®	1165:1173	Benepali®	1165:1173	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	19	theme	rapid	940:944	arg1	electrophoresis					961:975	a rapid, capillary gel electrophoresis	938:975	a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles	938:1235	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	19	theme	rapid	940:944	arg1	Enbrel®					1153:1159	Enbrel®	1153:1159	Enbrel®	1153:1159	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	3	20	theme	critical	620:627	arg1	attributes					637:646	the important critical quality attributes	606:646	the important critical quality attributes of glycoprotein biotherapeutics	606:678	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	1	21	theme	polypeptide	186:196	arg1	chains					198:203	the polypeptide chains	182:203	the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars	182:268	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	0	22	theme	Glycosimilarity	0:14	arg1	assessment					16:25	Glycosimilarity assessment	0:25	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.	0:151	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	1	23	theme	such	294:297	arg1	mechanisms					305:314	such major mechanisms	294:314	such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance	294:458	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	1	24	gly	glycoprotein	213:224	arg1	glycoprotein					213:224	most glycoprotein based biotherapeutics	208:246	most glycoprotein based biotherapeutics	208:246	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	3	25	theme	quality	629:635	arg1	attributes					637:646	the important critical quality attributes	606:646	the important critical quality attributes of glycoprotein biotherapeutics	606:678	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	5	26	link	N-linked	1206:1213	arg1	profiles					1228:1235	their N-linked carbohydrate profiles	1200:1235	their N-linked carbohydrate profiles	1200:1235	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	0	27	theme	biotherapeutics	30:44	arg1	assessment					16:25	Glycosimilarity assessment	0:25	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.	0:151	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	1	28	theme	major	299:303	arg1	mechanisms					305:314	such major mechanisms	294:314	such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance	294:458	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	5	29	dep	rapid	940:944	arg1	capillary					947:955	capillary	947:955	capillary	947:955	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	4	30	dep	both	793:796	arg1	innovator					798:806	innovator	798:806	innovator	798:806	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	4	31	theme	process	902:908	arg1	stages					874:879	all stages	870:879	all stages of the manufacturing process	870:908	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	7	32	theme	TNFα	1391:1394	arg1	binding					1396:1402	TNFα binding	1391:1402	TNFα binding	1391:1402	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	7	32	theme	TNFα	1391:1394	arg1	mechanism					1354:1362	the mechanism	1350:1362	the mechanism of action of etanercept	1350:1386	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	5	33	dep	based	977:981	arg1	Benepali®					1165:1173	Benepali®	1165:1173	Benepali®	1165:1173	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	33	dep	based	977:981	arg1	electrophoresis					961:975	a rapid, capillary gel electrophoresis	938:975	a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles	938:1235	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	33	dep	based	977:981	arg1	Enbrel®					1153:1159	Enbrel®	1153:1159	Enbrel®	1153:1159	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	0	34	theme	biosimilar	119:128	arg1	version					130:136	a biosimilar version	117:136	a biosimilar version of etanercept	117:150	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	1	35	theme	serum	444:448	arg1	clearance					450:458	serum clearance	444:458	serum clearance	444:458	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	3	36	theme	important	610:618	arg1	attributes					637:646	the important critical quality attributes	606:646	the important critical quality attributes of glycoprotein biotherapeutics	606:678	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	1	37	theme	most	208:211	arg1	biotherapeutics					232:246	most glycoprotein based biotherapeutics	208:246	most glycoprotein based biotherapeutics	208:246	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	0	38	theme	etanercept	141:150	arg1	version					130:136	a biosimilar version	117:136	a biosimilar version of etanercept	117:150	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	0	38	theme	etanercept	141:150	arg1	comparison					62:71	Quantitative comparison	49:71	Quantitative comparison of the N-glycosylation of the innovator	49:111	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	7	39	theme	etanercept	1377:1386	arg1	action					1367:1372	action	1367:1372	action of etanercept	1367:1386	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	3	40	theme	glycoprotein	651:662	arg1	biotherapeutics					664:678	glycoprotein biotherapeutics	651:678	glycoprotein biotherapeutics	651:678	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	6	41	from	Differences	1238:1248	arg1	glycans					1315:1321	high mannose glycans	1302:1321	high mannose glycans	1302:1321	Differences in sialylated, core fucosylated, galactosylated and high mannose glycans were all quantified.
29499461	6	41	from	Differences	1238:1248	arg1	sialylated					1253:1262	sialylated	1253:1262	sialylated	1253:1262	Differences in sialylated, core fucosylated, galactosylated and high mannose glycans were all quantified.
29499461	1	42	theme	glycoprotein	213:224	arg1	biotherapeutics					232:246	most glycoprotein based biotherapeutics	208:246	most glycoprotein based biotherapeutics	208:246	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	1	43	theme	actions	319:325	arg1	mechanisms					305:314	such major mechanisms	294:314	such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance	294:458	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	3	44	theme	biotherapeutics	664:678	arg1	attributes					637:646	the important critical quality attributes	606:646	the important critical quality attributes of glycoprotein biotherapeutics	606:678	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	1	45	theme	based	226:230	arg1	biotherapeutics					232:246	most glycoprotein based biotherapeutics	208:246	most glycoprotein based biotherapeutics	208:246	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	3	46	theme	biosimilar	708:717	arg1	counterparts					719:730	their biosimilar counterparts	702:730	their biosimilar counterparts	702:730	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	3	47	theme	attributes	637:646	arg1	one					599:601	one	599:601	one	599:601	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	3	47	theme	attributes	637:646	arg1	attributes					637:646	the important critical quality attributes	606:646	the important critical quality attributes of glycoprotein biotherapeutics	606:678	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	3	47	theme	attributes	637:646	arg1	Glycosylation					556:568	Glycosylation	556:568	Glycosylation	556:568	Glycosylation, therefore, is considered as one of the important critical quality attributes of glycoprotein biotherapeutics, and consequently for their biosimilar counterparts.
29499461	5	48	theme	N-linked	1206:1213	arg1	profiles					1228:1235	their N-linked carbohydrate profiles	1200:1235	their N-linked carbohydrate profiles	1200:1235	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	0	49	theme	Quantitative	49:60	arg1	comparison					62:71	Quantitative comparison	49:71	Quantitative comparison of the N-glycosylation of the innovator	49:111	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	1	50	theme	antibody-dependent	330:347	arg1	cytotoxicity					363:374	antibody-dependent cell-mediated cytotoxicity	330:374	antibody-dependent cell-mediated cytotoxicity	330:374	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	5	51	theme	biosimilar	1119:1128	arg1	version					1130:1136	a biosimilar version	1117:1136	a biosimilar version of etanercept	1117:1150	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	7	52	theme	action	1367:1372	arg1	binding					1396:1402	TNFα binding	1391:1402	TNFα binding	1391:1402	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	7	52	theme	action	1367:1372	arg1	mechanism					1354:1362	the mechanism	1350:1362	the mechanism of action of etanercept	1350:1386	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	6	53	theme	mannose	1307:1313	arg1	glycans					1315:1321	high mannose glycans	1302:1321	high mannose glycans	1302:1321	Differences in sialylated, core fucosylated, galactosylated and high mannose glycans were all quantified.
29499461	1	54	theme	cell-mediated	349:361	arg1	cytotoxicity					363:374	antibody-dependent cell-mediated cytotoxicity	330:374	antibody-dependent cell-mediated cytotoxicity	330:374	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	7	55	theme	critical	1438:1445	arg1	mannosylation					1410:1422	only mannosylation	1405:1422	only mannosylation	1405:1422	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	7	55	theme	critical	1438:1445	arg1	attribute					1455:1463	critical quality attribute	1438:1463	critical quality attribute for glycosimilarity assessment due to its influence on serum half-life	1438:1534	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	6	56	theme	high	1302:1305	arg1	glycans					1315:1321	high mannose glycans	1302:1321	high mannose glycans	1302:1321	Differences in sialylated, core fucosylated, galactosylated and high mannose glycans were all quantified.
29499461	4	57	theme	manufacturing	888:900	arg1	process					902:908	the manufacturing process	884:908	the manufacturing process	884:908	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	4	58	dep	products	823:830	arg1	both					793:796	both	793:796	both	793:796	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	4	58	dep	products	823:830	arg1	biosimilar					812:821	biosimilar	812:821	biosimilar	812:821	Thus, the carbohydrate moieties of such biopharmaceuticals (both innovator and biosimilar products) should be closely scrutinized during all stages of the manufacturing process.
29499461	5	59	theme	etanercept	1141:1150	arg1	version					1130:1136	a biosimilar version	1117:1136	a biosimilar version of etanercept	1117:1150	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	59	theme	etanercept	1141:1150	arg1	aspect					1034:1039	the glycosylation aspect	1016:1039	the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator	1016:1111	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	7	60	theme	quality	1447:1453	arg1	mannosylation					1410:1422	only mannosylation	1405:1422	only mannosylation	1405:1422	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	7	60	theme	quality	1447:1453	arg1	attribute					1455:1463	critical quality attribute	1438:1463	critical quality attribute for glycosimilarity assessment due to its influence on serum half-life	1438:1534	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	7	61	theme	glycosimilarity	1469:1483	arg1	assessment					1485:1494	glycosimilarity assessment	1469:1494	glycosimilarity assessment due to its influence on serum half-life	1469:1534	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	0	62	dep	assessment	16:25	arg1	version					130:136	a biosimilar version	117:136	a biosimilar version of etanercept	117:150	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	0	62	dep	assessment	16:25	arg1	comparison					62:71	Quantitative comparison	49:71	Quantitative comparison of the N-glycosylation of the innovator	49:111	Glycosimilarity assessment of biotherapeutics 1: Quantitative comparison of the N-glycosylation of the innovator and a biosimilar version of etanercept.
29499461	1	63	from	chains	198:203	arg1	biotherapeutics					232:246	most glycoprotein based biotherapeutics	208:246	most glycoprotein based biotherapeutics	208:246	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	1	63	from	chains	198:203	arg1	biosimilars					258:268	their biosimilars	252:268	their biosimilars	252:268	The carbohydrate moieties on the polypeptide chains in most glycoprotein based biotherapeutics and their biosimilars play essential roles in such major mechanisms of actions as antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, anti-inflammatory functions and serum clearance.
29499461	5	64	theme	gel	957:959	arg1	Benepali®					1165:1173	Benepali®	1165:1173	Benepali®	1165:1173	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	64	theme	gel	957:959	arg1	electrophoresis					961:975	a rapid, capillary gel electrophoresis	938:975	a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles	938:1235	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	5	64	theme	gel	957:959	arg1	Enbrel®					1153:1159	Enbrel®	1153:1159	Enbrel®	1153:1159	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
29499461	7	65	from	influence	1507:1515	arg1	half-life					1526:1534	serum half-life	1520:1534	serum half-life	1520:1534	Since the mechanism of action of etanercept is TNFα binding, only mannosylation was deemed as critical quality attribute for glycosimilarity assessment due to its influence on serum half-life.
29499461	5	66	dep	biosimilarity	1044:1056	arg1	referred					1059:1066	referred	1059:1066	referred to as glycosimilarity	1059:1088	In this paper we introduce a rapid, capillary gel electrophoresis based process to quantitatively assess the glycosylation aspect of biosimilarity (referred to as glycosimilarity) between the innovator and a biosimilar version of etanercept (Enbrel® and Benepali®, respectively), based on their N-linked carbohydrate profiles.
32184970	0	0	theme	Rapid	73:77	arg1	Validation					90:99	Enabling Rapid Target (In)Validation	64:99	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.	0:100	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	6	1	theme	intracellular	992:1004	arg1	concentrations					1006:1019	intracellular concentrations	992:1019	intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition	992:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	6	2	theme	damage	955:960	arg1	response					962:969	the DNA damage response	947:969	the DNA damage response	947:969	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	0	3	theme	Enabling	64:71	arg1	Validation					90:99	Enabling Rapid Target (In)Validation	64:99	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.	0:100	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	6	4	theme	concentrations	1006:1019	arg1	Elucidation					932:942	Elucidation	932:942	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition	932:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	3	5	from	ligand	456:461	arg1	interactions					567:578	polar interactions	561:578	polar interactions with residues Gly34 and Asp120	561:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	5	from	ligand	456:461	arg1	conformation					500:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation	466:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond	466:555	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	4	6	theme	O-	659:660	arg1	aryl					675:678	O- and N-linked aryl and alkyl aryl substituents	659:706	aryl	675:678	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	6	7	theme	DNA	951:953	arg1	damage					955:960	the DNA damage	947:960	the DNA damage response	947:969	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	6	8	theme	inhibition	1123:1132	arg1	function					1074:1081	a function	1072:1081	a function of MTH1 knockdown and/or small molecule inhibition	1072:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	6	9	theme	knockdown	1091:1099	arg1	function					1074:1081	a function	1072:1081	a function of MTH1 knockdown and/or small molecule inhibition	1072:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	0	10	theme	Target	79:84	arg1	Validation					90:99	Enabling Rapid Target (In)Validation	64:99	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.	0:100	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	6	11	theme	small	1108:1112	arg1	inhibition					1123:1132	small molecule inhibition	1108:1132	small molecule inhibition	1108:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	5	12	with	compound	841:848	arg1	properties					913:922	desirable pharmacokinetic properties	887:922	desirable pharmacokinetic properties	887:922	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	5	12	with	compound	841:848	arg1	profile					875:881	a suitable in vitro profile	855:881	a suitable in vitro profile	855:881	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	3	13	theme	acetamide	490:498	arg1	conformation					500:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation	466:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond	466:555	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	4	14	theme	aryl	690:693	arg1	substituents					695:706	O- and N-linked aryl and alkyl aryl substituents	659:706	substituents	695:706	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	5	15	theme	desirable	887:895	arg1	properties					913:922	desirable pharmacokinetic properties	887:922	desirable pharmacokinetic properties	887:922	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	3	16	theme	5	431:431	arg1	Cocrystallization					410:426	Cocrystallization	410:426	Cocrystallization of 5 with MTH1	410:441	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	4	17	theme	potent	732:737	arg1	pyrimidine-2,4,6-triamine					739:763	potent pyrimidine-2,4,6-triamine 25	732:766	potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM)	732:783	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	4	17	theme	potent	732:737	arg1	nM					781:782	IC50 = 0.49 nM	769:782	IC50 = 0.49 nM	769:782	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	4	18	theme	compound	639:646	arg1	Modification					612:623	Modification	612:623	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents	612:706	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	2	19	theme	potent	369:374	arg1	nM					405:406	IC50 = 0.043 nM	392:406	IC50 = 0.043 nM	392:406	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	2	19	theme	potent	369:374	arg1	inhibitor					381:389	a highly potent MTH1 inhibitor	360:389	a highly potent MTH1 inhibitor (IC50 = 0.043 nM)	360:407	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	2	19	theme	potent	369:374	arg1	Tetrahydronaphthyridine					308:330	Tetrahydronaphthyridine 5	308:332	Tetrahydronaphthyridine 5	308:332	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	0	20	theme	In	87:88	arg1	Validation					90:99	Enabling Rapid Target (In)Validation	64:99	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.	0:100	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	5	21	dep	in	866:867	arg1	vitro					869:873	vitro	869:873	vitro	869:873	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	3	22	theme	pyridin-2-yl	477:488	arg1	conformation					500:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation	466:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond	466:555	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	1	23	theme	differentiated	150:163	arg1	inhibitors					191:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	2	24	theme	=	397:397	arg1	nM					405:406	IC50 = 0.043 nM	392:406	IC50 = 0.043 nM	392:406	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	2	24	theme	=	397:397	arg1	inhibitor					381:389	a highly potent MTH1 inhibitor	360:389	a highly potent MTH1 inhibitor (IC50 = 0.043 nM)	360:407	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	6	25	theme	oxidized	1034:1041	arg1	oxo-NTPs					1024:1031	oxo-NTPs	1024:1031	oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition	1024:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	6	25	theme	oxidized	1034:1041	arg1	triphosphates					1054:1066	oxidized nucleoside triphosphates	1034:1066	oxidized nucleoside triphosphates	1034:1066	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	5	26	from	profile	875:881	arg1	rat					927:929	rat	927:929	rat	927:929	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	6	27	theme	molecule	1114:1121	arg1	inhibition					1123:1132	small molecule inhibition	1108:1132	small molecule inhibition	1108:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	3	28	with	conformation	500:511	arg1	Asp120					604:609	Asp120	604:609	Asp120	604:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	28	with	conformation	500:511	arg1	Gly34					594:598	Gly34	594:598	Gly34	594:598	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	28	with	conformation	500:511	arg1	residues					585:592	residues Gly34 and Asp120	585:609	residues Gly34 and Asp120	585:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	1	29	theme	potent	165:170	arg1	inhibitors					191:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	1	30	theme	oncology	253:260	arg1	MTH1					242:245	MTH1	242:245	MTH1	242:245	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	1	30	theme	oncology	253:260	arg1	target					262:267	an oncology target	250:267	an oncology target	250:267	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	6	31	theme	oxo-NTPs	1024:1031	arg1	concentrations					1006:1019	intracellular concentrations	992:1019	intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition	992:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	6	31	theme	oxo-NTPs	1024:1031	arg1	response					962:969	the DNA damage response	947:969	the DNA damage response	947:969	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	6	31	theme	oxo-NTPs	1024:1031	arg1	viability					977:985	cell viability	972:985	cell viability	972:985	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	3	32	theme	key	524:526	arg1	bond					552:555	a key intramolecular hydrogen bond	522:555	a key intramolecular hydrogen bond	522:555	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	7	33	theme	oncology	1234:1241	arg1	target					1243:1248	an oncology target	1231:1248	an oncology target	1231:1248	Based on our findings, we were unable to provide evidence to further pursue MTH1 as an oncology target.
32184970	7	33	theme	oncology	1234:1241	arg1	MTH1					1223:1226	MTH1	1223:1226	MTH1	1223:1226	Based on our findings, we were unable to provide evidence to further pursue MTH1 as an oncology target.
32184970	4	34	theme	literature	628:637	arg1	compound					639:646	literature compound TH287	628:652	literature compound TH287	628:652	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	2	35	theme	0.043	399:403	arg1	nM					405:406	IC50 = 0.043 nM	392:406	IC50 = 0.043 nM	392:406	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	2	35	theme	0.043	399:403	arg1	inhibitor					381:389	a highly potent MTH1 inhibitor	360:389	a highly potent MTH1 inhibitor (IC50 = 0.043 nM)	360:407	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	4	36	theme	IC50	769:772	arg1	pyrimidine-2,4,6-triamine					739:763	potent pyrimidine-2,4,6-triamine 25	732:766	potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM)	732:783	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	4	36	theme	IC50	769:772	arg1	nM					781:782	IC50 = 0.49 nM	769:782	IC50 = 0.49 nM	769:782	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	5	37	theme	pharmacokinetic	897:911	arg1	properties					913:922	desirable pharmacokinetic properties	887:922	desirable pharmacokinetic properties	887:922	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	2	38	theme	IC50	392:395	arg1	nM					405:406	IC50 = 0.043 nM	392:406	IC50 = 0.043 nM	392:406	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	2	38	theme	IC50	392:395	arg1	inhibitor					381:389	a highly potent MTH1 inhibitor	360:389	a highly potent MTH1 inhibitor (IC50 = 0.043 nM)	360:407	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	0	39	theme	Potent	13:18	arg1	Inhibitors					39:48	Potent and Selective MTH1 Inhibitors	13:48	Potent and Selective MTH1 Inhibitors	13:48	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	3	40	with	Cocrystallization	410:426	arg1	MTH1					438:441	MTH1	438:441	MTH1	438:441	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	6	41	theme	nucleoside	1043:1052	arg1	oxo-NTPs					1024:1031	oxo-NTPs	1024:1031	oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition	1024:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	6	41	theme	nucleoside	1043:1052	arg1	triphosphates					1054:1066	oxidized nucleoside triphosphates	1034:1066	oxidized nucleoside triphosphates	1034:1066	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	1	42	theme	MTH1	186:189	arg1	inhibitors					191:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	0	43	theme	MTH1	34:37	arg1	Inhibitors					39:48	Potent and Selective MTH1 Inhibitors	13:48	Potent and Selective MTH1 Inhibitors	13:48	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	5	44	theme	in	866:867	arg1	profile					875:881	a suitable in vitro profile	855:881	a suitable in vitro profile	855:881	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	5	45	theme	selective	826:834	arg1	compound					841:848	a highly selective lead compound	817:848	a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat	817:929	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	1	46	theme	inhibitors	191:200	arg1	discovery					118:126	the discovery	114:126	the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation	114:305	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	0	47	theme	Selective	24:32	arg1	Inhibitors					39:48	Potent and Selective MTH1 Inhibitors	13:48	Potent and Selective MTH1 Inhibitors	13:48	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	4	48	theme	=	774:774	arg1	pyrimidine-2,4,6-triamine					739:763	potent pyrimidine-2,4,6-triamine 25	732:766	potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM)	732:783	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	4	48	theme	=	774:774	arg1	nM					781:782	IC50 = 0.49 nM	769:782	IC50 = 0.49 nM	769:782	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	2	49	theme	MTH1	376:379	arg1	nM					405:406	IC50 = 0.043 nM	392:406	IC50 = 0.043 nM	392:406	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	2	49	theme	MTH1	376:379	arg1	inhibitor					381:389	a highly potent MTH1 inhibitor	360:389	a highly potent MTH1 inhibitor (IC50 = 0.043 nM)	360:407	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	2	49	theme	MTH1	376:379	arg1	Tetrahydronaphthyridine					308:330	Tetrahydronaphthyridine 5	308:332	Tetrahydronaphthyridine 5	308:332	Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM).
32184970	1	50	theme	target	285:290	arg1	validation					296:305	target (in)validation	285:305	target (in)validation	285:305	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	4	51	with	Modification	612:623	arg1	aryl					675:678	O- and N-linked aryl and alkyl aryl substituents	659:706	aryl	675:678	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	4	51	with	Modification	612:623	arg1	substituents					695:706	O- and N-linked aryl and alkyl aryl substituents	659:706	substituents	695:706	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	3	52	theme	intramolecular	528:541	arg1	bond					552:555	a key intramolecular hydrogen bond	522:555	a key intramolecular hydrogen bond	522:555	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	5	53	theme	suitable	857:864	arg1	profile					875:881	a suitable in vitro profile	855:881	a suitable in vitro profile	855:881	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	0	54	theme	Inhibitors	39:48	arg1	Discovery					0:8	Discovery	0:8	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.	0:100	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	3	55	theme	hydrogen	543:550	arg1	bond					552:555	a key intramolecular hydrogen bond	522:555	a key intramolecular hydrogen bond	522:555	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	4	56	theme	N-linked	666:673	arg1	aryl					675:678	O- and N-linked aryl and alkyl aryl substituents	659:706	aryl	675:678	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	1	57	theme	in	293:294	arg1	validation					296:305	target (in)validation	285:305	target (in)validation	285:305	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	6	58	theme	cell	972:975	arg1	viability					977:985	cell viability	972:985	cell viability	972:985	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	4	59	theme	alkyl	684:688	arg1	substituents					695:706	O- and N-linked aryl and alkyl aryl substituents	659:706	substituents	695:706	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	5	60	from	properties	913:922	arg1	rat					927:929	rat	927:929	rat	927:929	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	6	61	theme	viability	977:985	arg1	Elucidation					932:942	Elucidation	932:942	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition	932:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	4	62	link	N-linked	666:673	arg1	aryl					675:678	O- and N-linked aryl and alkyl aryl substituents	659:706	aryl	675:678	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	4	63	theme	pyrimidine-2,4,6-triamine	739:763	arg1	discovery					719:727	the discovery	715:727	the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM)	715:783	Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM).
32184970	6	64	theme	MTH1	1086:1089	arg1	knockdown					1091:1099	MTH1 knockdown	1086:1099	MTH1 knockdown	1086:1099	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
32184970	1	65	theme	subsequent	212:221	arg1	use					223:225	their subsequent use	206:225	their subsequent use	206:225	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	3	66	dep	residues	585:592	arg1	Asp120					604:609	Asp120	604:609	Asp120	604:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	66	dep	residues	585:592	arg1	Gly34					594:598	Gly34	594:598	Gly34	594:598	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	66	dep	residues	585:592	arg1	residues					585:592	residues Gly34 and Asp120	585:609	residues Gly34 and Asp120	585:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	67	theme	polar	561:565	arg1	interactions					567:578	polar interactions	561:578	polar interactions with residues Gly34 and Asp120	561:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	1	68	theme	selective	176:184	arg1	inhibitors					191:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	three structurally differentiated potent and selective MTH1 inhibitors	131:200	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	5	69	theme	lead	836:839	arg1	compound					841:848	a highly selective lead compound	817:848	a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat	817:929	Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat.
32184970	1	70	theme	use	223:225	arg1	discovery					118:126	the discovery	114:126	the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation	114:305	We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncology target, culminating in target (in)validation.
32184970	3	71	with	interactions	567:578	arg1	Asp120					604:609	Asp120	604:609	Asp120	604:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	71	with	interactions	567:578	arg1	Gly34					594:598	Gly34	594:598	Gly34	594:598	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	3	71	with	interactions	567:578	arg1	residues					585:592	residues Gly34 and Asp120	585:609	residues Gly34 and Asp120	585:609	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	0	72	dep	Discovery	0:8	arg1	Validation					90:99	Enabling Rapid Target (In)Validation	64:99	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.	0:100	Discovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation.
32184970	3	73	theme	Φ-cis-N-	468:475	arg1	conformation					500:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation	466:511	a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond	466:555	Cocrystallization of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramolecular hydrogen bond and polar interactions with residues Gly34 and Asp120.
32184970	6	74	theme	response	962:969	arg1	Elucidation					932:942	Elucidation	932:942	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition	932:1132	Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small molecule inhibition was studied.
30506260	4	0	theme	ELISA	994:998	arg1	test					1000:1003	a highly sensitive and specific indirect ELISA test	953:1003	a highly sensitive and specific indirect ELISA test	953:1003	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	3	1	theme	expression	697:706	arg1	system					708:713	any malaria protein expression system	677:713	any malaria protein expression system	677:713	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	2	link	N-linked	752:759	arg1	machinery					775:783	N-linked glycosylation machinery	752:783	N-linked glycosylation machinery	752:783	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	3	dep	those	565:569	arg1	quality					666:672	a valuable quality	655:672	those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system	565:713	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	5	4	theme	expressed	1113:1121	arg1	PfCelTOS					1135:1142	expressed recombinant PfCelTOS	1113:1142	expressed recombinant PfCelTOS	1113:1142	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	0	5	theme	reinhardtii	79:89	arg1	Use					109:111	its Potential Use	95:111	its Potential Use in Detection of Malaria	95:135	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	0	5	theme	reinhardtii	79:89	arg1	Chloroplast					50:60	the Chloroplast	46:60	the Chloroplast of Chlamydomonas reinhardtii	46:89	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	5	6	theme	soluble	1161:1167	arg1	use					1326:1328	the potential use	1312:1328	the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests	1312:1391	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	6	theme	soluble	1161:1167	arg1	protein					1201:1207	a soluble, properly folded and functional protein	1159:1207	a soluble, properly folded and functional protein	1159:1207	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	1	7	theme	serious	151:157	arg1	disease					200:206	a serious but preventable and treatable infectious disease	149:206	a serious but preventable and treatable infectious disease that is found in over 100 countries around the world	149:259	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	1	7	theme	serious	151:157	arg1	Malaria					138:144	Malaria	138:144	Malaria	138:144	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	0	8	theme	Potential	99:107	arg1	Use					109:111	its Potential Use	95:111	its Potential Use in Detection of Malaria	95:135	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	0	9	from	Expression	0:9	arg1	Use					109:111	its Potential Use	95:111	its Potential Use in Detection of Malaria	95:135	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	0	9	from	Expression	0:9	arg1	Chloroplast					50:60	the Chloroplast	46:60	the Chloroplast of Chlamydomonas reinhardtii	46:89	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	2	10	theme	rapid	274:278	arg1	diagnosis					280:288	Correct and rapid diagnosis	262:288	Correct and rapid diagnosis of malaria infection	262:309	Correct and rapid diagnosis of malaria infection can rescue the patient of getting sicker and reduces the risk of disease spreading among humans.
30506260	5	11	theme	potential	1316:1324	arg1	protein					1201:1207	a soluble, properly folded and functional protein	1159:1207	a soluble, properly folded and functional protein	1159:1207	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	11	theme	potential	1316:1324	arg1	use					1326:1328	the potential use	1312:1328	the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests	1312:1391	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	3	12	gly	glycosylate	633:643	arg1	proteins					645:652	proteins	645:652	proteins	645:652	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	0	13	from	Chloroplast	50:60	arg1	Detection					116:124	Detection	116:124	Detection of Malaria	116:135	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	4	14	theme	Plasmodium	876:885	arg1	falciparum					887:896	Plasmodium falciparum	876:896	Plasmodium falciparum	876:896	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	3	15	theme	proteins	545:552	arg1	capable					518:524	capable	518:524	capable	518:524	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	4	16	theme	sensitive	962:970	arg1	ELISA					994:998	a highly sensitive and specific indirect ELISA	953:998	a highly sensitive and specific indirect ELISA test	953:1003	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	5	17	theme	recombinant	1123:1133	arg1	PfCelTOS					1135:1142	expressed recombinant PfCelTOS	1113:1142	expressed recombinant PfCelTOS	1113:1142	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	2	18	theme	Correct	262:268	arg1	diagnosis					280:288	Correct and rapid diagnosis	262:288	Correct and rapid diagnosis of malaria infection	262:309	Correct and rapid diagnosis of malaria infection can rescue the patient of getting sicker and reduces the risk of disease spreading among humans.
30506260	5	19	theme	diagnosis	1377:1385	arg1	tests					1387:1391	diagnosis tests	1377:1391	diagnosis tests	1377:1391	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	3	20	theme	reinhardtii	422:432	arg1	chloroplast					434:444	Chlamydomonas reinhardtii chloroplast	408:444	Chlamydomonas reinhardtii chloroplast	408:444	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	20	theme	reinhardtii	422:432	arg1	platform					463:470	an attractive platform	449:470	an attractive platform for expressing malaria antigens	449:502	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	21	theme	system	708:713	arg1	quality					666:672	a valuable quality	655:672	those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system	565:713	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	4	22	theme	sporozoites	842:852	arg1	antigen					863:869	ookinetes and sporozoites (CelTOS) antigen	828:869	ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum	828:896	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	3	23	theme	folding	529:535	arg1	proteins					545:552	folding complex proteins	529:552	folding complex proteins	529:552	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	23	theme	folding	529:535	arg1	those					565:569	those	565:569	those	565:569	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	1	24	theme	preventable	163:173	arg1	disease					200:206	a serious but preventable and treatable infectious disease	149:206	a serious but preventable and treatable infectious disease that is found in over 100 countries around the world	149:259	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	1	24	theme	preventable	163:173	arg1	Malaria					138:144	Malaria	138:144	Malaria	138:144	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	4	25	theme	indirect	985:992	arg1	ELISA					994:998	a highly sensitive and specific indirect ELISA	953:998	a highly sensitive and specific indirect ELISA test	953:1003	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	5	26	theme	C.	1216:1217	arg1	chloroplast					1231:1241	C. reinhardtii chloroplast	1216:1241	C. reinhardtii chloroplast	1216:1241	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	4	27	theme	specific	976:983	arg1	ELISA					994:998	a highly sensitive and specific indirect ELISA	953:998	a highly sensitive and specific indirect ELISA test	953:1003	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	2	28	theme	infection	301:309	arg1	diagnosis					280:288	Correct and rapid diagnosis	262:288	Correct and rapid diagnosis of malaria infection	262:309	Correct and rapid diagnosis of malaria infection can rescue the patient of getting sicker and reduces the risk of disease spreading among humans.
30506260	2	29	theme	malaria	293:299	arg1	infection					301:309	malaria infection	293:309	malaria infection	293:309	Correct and rapid diagnosis of malaria infection can rescue the patient of getting sicker and reduces the risk of disease spreading among humans.
30506260	1	30	theme	treatable	179:187	arg1	disease					200:206	a serious but preventable and treatable infectious disease	149:206	a serious but preventable and treatable infectious disease that is found in over 100 countries around the world	149:259	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	1	30	theme	treatable	179:187	arg1	Malaria					138:144	Malaria	138:144	Malaria	138:144	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	0	31	theme	PfCelTOS	26:33	arg1	Antigen					35:41	Recombinant PfCelTOS Antigen	14:41	Recombinant PfCelTOS Antigen	14:41	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	3	32	theme	N-linked	752:759	arg1	machinery					775:783	N-linked glycosylation machinery	752:783	N-linked glycosylation machinery	752:783	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	4	33	theme	ookinetes	828:836	arg1	antigen					863:869	ookinetes and sporozoites (CelTOS) antigen	828:869	ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum	828:896	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	1	34	theme	infectious	189:198	arg1	disease					200:206	a serious but preventable and treatable infectious disease	149:206	a serious but preventable and treatable infectious disease that is found in over 100 countries around the world	149:259	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	1	34	theme	infectious	189:198	arg1	Malaria					138:144	Malaria	138:144	Malaria	138:144	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	0	35	theme	Recombinant	14:24	arg1	Antigen					35:41	Recombinant PfCelTOS Antigen	14:41	Recombinant PfCelTOS Antigen	14:41	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	3	36	theme	Plasmodium	726:735	arg1	parasite					737:744	the Plasmodium parasite	722:744	the Plasmodium parasite	722:744	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	5	37	from	donors	1295:1300	arg1	sera					1268:1271	sera	1268:1271	sera from malaria-positive donors	1268:1300	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	38	theme	malaria	1357:1363	arg1	antigen					1365:1371	a malaria antigen	1355:1371	a malaria antigen for diagnosis tests	1355:1391	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	39	theme	reinhardtii	1219:1229	arg1	chloroplast					1231:1241	C. reinhardtii chloroplast	1216:1241	C. reinhardtii chloroplast	1216:1241	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	4	40	theme	reinhardtii	937:947	arg1	chloroplast					919:929	the chloroplast	915:929	the chloroplast of C. reinhardtii	915:947	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	3	41	theme	Chlamydomonas	408:420	arg1	reinhardtii					422:432	Chlamydomonas reinhardtii	408:432	Chlamydomonas reinhardtii chloroplast	408:444	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	2	42	theme	spreading	384:392	arg1	risk					368:371	the risk	364:371	the risk of disease spreading among humans	364:405	Correct and rapid diagnosis of malaria infection can rescue the patient of getting sicker and reduces the risk of disease spreading among humans.
30506260	0	43	theme	Antigen	35:41	arg1	Expression					0:9	Expression	0:9	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.	0:136	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	0	44	theme	Malaria	129:135	arg1	Detection					116:124	Detection	116:124	Detection of Malaria	116:135	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	1	45	located	found	216:220	arg2	disease					200:206	a serious but preventable and treatable infectious disease	149:206	a serious but preventable and treatable infectious disease that is found in over 100 countries around the world	149:259	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	1	45	located	found	216:220	arg2	Malaria					138:144	Malaria	138:144	Malaria	138:144	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	1	45	located	found	216:220	arg1	countries					234:242	over 100 countries	225:242	over 100 countries around the world	225:259	Malaria is a serious but preventable and treatable infectious disease that is found in over 100 countries around the world.
30506260	2	46	theme	disease	376:382	arg1	spreading					384:392	disease spreading	376:392	disease spreading	376:392	Correct and rapid diagnosis of malaria infection can rescue the patient of getting sicker and reduces the risk of disease spreading among humans.
30506260	5	47	theme	folded	1179:1184	arg1	use					1326:1328	the potential use	1312:1328	the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests	1312:1391	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	47	theme	folded	1179:1184	arg1	protein					1201:1207	a soluble, properly folded and functional protein	1159:1207	a soluble, properly folded and functional protein	1159:1207	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	3	48	theme	disulfide	581:589	arg1	formation					596:604	disulfide bond formation	581:604	disulfide bond formation	581:604	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	49	theme	malaria	487:493	arg1	antigens					495:502	expressing malaria antigens	476:502	expressing malaria antigens	476:502	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	50	theme	malaria	681:687	arg1	system					708:713	any malaria protein expression system	677:713	any malaria protein expression system	677:713	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	51	theme	glycosylation	761:773	arg1	machinery					775:783	N-linked glycosylation machinery	752:783	N-linked glycosylation machinery	752:783	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	4	52	from	falciparum	887:896	arg1	antigen					863:869	ookinetes and sporozoites (CelTOS) antigen	828:869	ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum	828:896	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	3	53	theme	bond	591:594	arg1	formation					596:604	disulfide bond formation	581:604	disulfide bond formation	581:604	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	5	54	theme	functional	1190:1199	arg1	use					1326:1328	the potential use	1312:1328	the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests	1312:1391	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	54	theme	functional	1190:1199	arg1	protein					1201:1207	a soluble, properly folded and functional protein	1159:1207	a soluble, properly folded and functional protein	1159:1207	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	0	55	from	Use	109:111	arg1	Detection					116:124	Detection	116:124	Detection of Malaria	116:135	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	3	56	theme	complex	537:543	arg1	proteins					545:552	folding complex proteins	529:552	folding complex proteins	529:552	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	56	theme	complex	537:543	arg1	those					565:569	those	565:569	those	565:569	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	57	theme	expressing	476:485	arg1	antigens					495:502	expressing malaria antigens	476:502	expressing malaria antigens	476:502	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	5	58	theme	expressed	1333:1341	arg1	PfCelTOS					1343:1350	expressed PfCelTOS	1333:1350	expressed PfCelTOS	1333:1350	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	0	59	theme	Chlamydomonas	65:77	arg1	reinhardtii					79:89	Chlamydomonas reinhardtii	65:89	Chlamydomonas reinhardtii	65:89	Expression of Recombinant PfCelTOS Antigen in the Chloroplast of Chlamydomonas reinhardtii and its Potential Use in Detection of Malaria.
30506260	3	60	theme	valuable	657:664	arg1	quality					666:672	a valuable quality	655:672	those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system	565:713	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	4	61	theme	Cell-traversal	801:814	arg1	protein					816:822	Cell-traversal protein	801:822	Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum	801:896	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	3	62	theme	attractive	452:461	arg1	chloroplast					434:444	Chlamydomonas reinhardtii chloroplast	408:444	Chlamydomonas reinhardtii chloroplast	408:444	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	3	62	theme	attractive	452:461	arg1	platform					463:470	an attractive platform	449:470	an attractive platform for expressing malaria antigens	449:502	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	5	63	theme	PfCelTOS	1343:1350	arg1	protein					1201:1207	a soluble, properly folded and functional protein	1159:1207	a soluble, properly folded and functional protein	1159:1207	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	63	theme	PfCelTOS	1343:1350	arg1	use					1326:1328	the potential use	1312:1328	the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests	1312:1391	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	5	64	theme	indirect	1247:1254	arg1	ELISA					1256:1260	indirect ELISA	1247:1260	indirect ELISA using sera from malaria-positive donors	1247:1300	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30506260	3	65	theme	protein	689:695	arg1	system					708:713	any malaria protein expression system	677:713	any malaria protein expression system	677:713	Chlamydomonas reinhardtii chloroplast is an attractive platform for expressing malaria antigens because it is capable of folding complex proteins, including those requiring disulfide bond formation, while lack the ability to glycosylate proteins; a valuable quality of any malaria protein expression system, since the Plasmodium parasite lacks N-linked glycosylation machinery.
30506260	4	66	theme	expressed	1040:1048	arg1	PfCelTOS					1050:1057	expressed PfCelTOS	1040:1057	expressed PfCelTOS	1040:1057	In this study, Cell-traversal protein for ookinetes and sporozoites (CelTOS) antigen from Plasmodium falciparum was expressed in the chloroplast of C. reinhardtii and a highly sensitive and specific indirect ELISA test was developed using C. reinhardtii expressed PfCelTOS to detect malaria.
30506260	5	67	theme	malaria-positive	1278:1293	arg1	donors					1295:1300	malaria-positive donors	1278:1300	malaria-positive donors	1278:1300	Results obtained demonstrated that expressed recombinant PfCelTOS accumulates as a soluble, properly folded and functional protein within C. reinhardtii chloroplast and indirect ELISA using sera from malaria-positive donors suggested the potential use of expressed PfCelTOS as a malaria antigen for diagnosis tests.
30606265	0	0	theme	pleuropneumoniae	89:104	arg1	development					59:69	the development	55:69	the development of Actinobacillus pleuropneumoniae	55:104	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
30606265	5	1	theme	glucose	795:801	arg1	polymer					803:809	a glucose polymer	793:809	a glucose polymer	793:809	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	7	2	theme	A.	1118:1119	arg1	infection					1138:1146	A. pleuropneumoniae infection	1118:1146	A. pleuropneumoniae infection	1118:1146	Both the toxins and glycosylation system represent potential targets for the basis of a vaccine against A. pleuropneumoniae infection.
30606265	11	3	theme	toxin	1625:1629	arg1	fragment					1631:1638	toxin fragment	1625:1638	toxin fragment	1625:1638	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	7	4	theme	glycosylation	1034:1046	arg1	system					1048:1053	glycosylation system	1034:1053	glycosylation system	1034:1053	Both the toxins and glycosylation system represent potential targets for the basis of a vaccine against A. pleuropneumoniae infection.
30606265	6	5	theme	A.	993:994	arg1	pleuropneumoniae					996:1011	A. pleuropneumoniae	993:1011	A. pleuropneumoniae	993:1011	However to date, there is little evidence to suggest that such a glucose polymer is formed on its target peptides in A. pleuropneumoniae.
30606265	0	6	theme	Actinobacillus	74:87	arg1	pleuropneumoniae					89:104	Actinobacillus pleuropneumoniae	74:104	Actinobacillus pleuropneumoniae	74:104	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
30606265	0	7	from	glycoengineering	12:27	arg1	development					59:69	the development	55:69	the development of Actinobacillus pleuropneumoniae	55:104	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
30606265	7	8	theme	pleuropneumoniae	1121:1136	arg1	infection					1138:1146	A. pleuropneumoniae infection	1118:1146	A. pleuropneumoniae infection	1118:1146	Both the toxins and glycosylation system represent potential targets for the basis of a vaccine against A. pleuropneumoniae infection.
30606265	1	9	theme	porcine	200:206	arg1	pleuropneumonia					208:222	porcine pleuropneumonia	200:222	porcine pleuropneumonia	200:222	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	10	10	theme	ngt	1476:1478	arg1	copy					1468:1471	A single chromosomal copy	1447:1471	A single chromosomal copy of ngt and agt	1447:1486	A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.
30606265	11	11	theme	conserved	1647:1655	arg1	glycan					1657:1662	a conserved glycan	1645:1662	a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression	1645:1765	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	7	12	theme	vaccine	1102:1108	arg1	basis					1091:1095	the basis	1087:1095	the basis of a vaccine against A. pleuropneumoniae infection	1087:1146	Both the toxins and glycosylation system represent potential targets for the basis of a vaccine against A. pleuropneumoniae infection.
30606265	6	13	theme	little	902:907	arg1	evidence					909:916	little evidence	902:916	little evidence to suggest that such a glucose polymer is formed on its target peptides in A. pleuropneumoniae	902:1011	However to date, there is little evidence to suggest that such a glucose polymer is formed on its target peptides in A. pleuropneumoniae.
30606265	5	14	theme	Plasmid-borne	701:713	arg1	expression					727:736	Plasmid-borne recombinant expression	701:736	Plasmid-borne recombinant expression of these genes in E. coli	701:762	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	6	15	theme	target	974:979	arg1	peptides					981:988	its target peptides	970:988	its target peptides in A. pleuropneumoniae	970:1011	However to date, there is little evidence to suggest that such a glucose polymer is formed on its target peptides in A. pleuropneumoniae.
30606265	3	16	theme	glucose	540:546	arg1	residues					548:555	glucose residues	540:555	glucose residues	540:555	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	3	17	with	adhesins	526:533	arg1	residues					548:555	glucose residues	540:555	glucose residues	540:555	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	1	18	theme	pleuropneumonia	208:222	arg1	agent					191:195	the causative agent	177:195	the causative agent of porcine pleuropneumonia	177:222	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	1	18	theme	pleuropneumonia	208:222	arg1	pleuropneumoniae					157:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	8	19	theme	vaccine	1242:1248	arg1	candidates					1250:1259	glycoconjugate vaccine candidates	1227:1259	glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose	1227:1315	RESULTS In this study, we developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose.
30606265	8	20	theme	glycoconjugate	1227:1240	arg1	candidates					1250:1259	glycoconjugate vaccine candidates	1227:1259	glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose	1227:1315	RESULTS In this study, we developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose.
30606265	10	21	theme	single	1449:1454	arg1	copy					1468:1471	A single chromosomal copy	1447:1471	A single chromosomal copy of ngt and agt	1447:1486	A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.
30606265	5	22	theme	acceptor	850:857	arg1	NX					867:868	NX	867:868	NX(S/T)	867:873	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	5	22	theme	acceptor	850:857	arg1	sequon					859:864	the appropriate acceptor sequon	834:864	the appropriate acceptor sequon	834:864	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	5	23	theme	appropriate	838:848	arg1	NX					867:868	NX	867:868	NX(S/T)	867:873	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	5	23	theme	appropriate	838:848	arg1	sequon					859:864	the appropriate acceptor sequon	834:864	the appropriate acceptor sequon	834:864	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	5	24	theme	polymer	803:809	arg1	production					779:788	the production	775:788	the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T)	775:873	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	10	25	theme	agt	1484:1486	arg1	copy					1468:1471	A single chromosomal copy	1447:1471	A single chromosomal copy of ngt and agt	1447:1486	A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.
30606265	10	26	theme	chromosomal	1456:1466	arg1	copy					1468:1471	A single chromosomal copy	1447:1471	A single chromosomal copy of ngt and agt	1447:1486	A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.
30606265	2	27	theme	haemolytic	349:358	arg1	toxins					360:365	haemolytic toxins	349:365	haemolytic toxins	349:365	Virulence can largely be attributed to the secretion of a series of haemolytic toxins, which are highly immunogenic.
30606265	8	28	theme	toxin	1281:1285	arg1	fragments					1287:1295	soluble toxin fragments	1273:1295	soluble toxin fragments modified by glucose	1273:1315	RESULTS In this study, we developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose.
30606265	0	29	theme	Cytoplasmic	0:10	arg1	glycoengineering					12:27	Cytoplasmic glycoengineering	0:27	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae	0:104	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
30606265	11	30	theme	disease	1747:1753	arg1	progression					1755:1765	disease progression	1747:1765	disease progression	1747:1765	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	6	31	from	peptides	981:988	arg1	pleuropneumoniae					996:1011	A. pleuropneumoniae	993:1011	A. pleuropneumoniae	993:1011	However to date, there is little evidence to suggest that such a glucose polymer is formed on its target peptides in A. pleuropneumoniae.
30606265	8	32	theme	soluble	1273:1279	arg1	fragments					1287:1295	soluble toxin fragments	1273:1295	soluble toxin fragments modified by glucose	1273:1315	RESULTS In this study, we developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose.
30606265	0	33	theme	Apx	32:34	arg1	toxin					36:40	Apx toxin	32:40	Apx toxin fragments	32:50	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
30606265	4	34	theme	N-glycosyl	597:606	arg1	transferase					608:618	the soluble N-glycosyl transferase	585:618	the soluble N-glycosyl transferase	585:618	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	4	34	theme	N-glycosyl	597:606	arg1	Central					558:564	Central	558:564	Central	558:564	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	4	34	theme	N-glycosyl	597:606	arg1	ngt					621:623	ngt	621:623	ngt	621:623	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	5	35	theme	genes	747:751	arg1	expression					727:736	Plasmid-borne recombinant expression	701:736	Plasmid-borne recombinant expression of these genes in E. coli	701:762	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	2	36	theme	series	339:344	arg1	secretion					324:332	the secretion	320:332	the secretion	320:332	Virulence can largely be attributed to the secretion of a series of haemolytic toxins, which are highly immunogenic.
30606265	2	36	theme	series	339:344	arg1	immunogenic					385:395	immunogenic	385:395	immunogenic	385:395	Virulence can largely be attributed to the secretion of a series of haemolytic toxins, which are highly immunogenic.
30606265	1	37	theme	major	241:245	arg1	burden					247:252	a major burden	239:252	a major burden to the livestock industry	239:278	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	10	38	theme	short	1542:1546	arg1	glycan					1548:1553	a short glycan	1540:1553	a short glycan	1540:1553	A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.
30606265	11	39	theme	important	1711:1719	arg1	epitopes					1702:1709	generating epitopes	1691:1709	generating epitopes important for both colonisation and disease progression	1691:1765	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	1	40	theme	BACKGROUND	131:140	arg1	agent					191:195	the causative agent	177:195	the causative agent of porcine pleuropneumonia	177:222	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	1	40	theme	BACKGROUND	131:140	arg1	pleuropneumoniae					157:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	3	41	theme	weight	519:524	arg1	adhesins					526:533	high molecular weight adhesins	504:533	high molecular weight adhesins with glucose residues	504:555	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	0	42	theme	fragments	42:50	arg1	glycoengineering					12:27	Cytoplasmic glycoengineering	0:27	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae	0:104	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
30606265	9	43	theme	coli	1378:1381	arg1	chromosome					1352:1361	the chromosome	1348:1361	the chromosome of Escherichia coli in order to generate a native-like operon for glycoengineering	1348:1444	We transferred ngt and agt to the chromosome of Escherichia coli in order to generate a native-like operon for glycoengineering.
30606265	5	44	from	production	779:788	arg1	peptides					814:821	peptides	814:821	peptides containing the appropriate acceptor sequon, NX(S/T)	814:873	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	11	45	dep	glycan	1657:1662	arg1	offers					1664:1669	offers	1664:1669	offers a novel approach to generating epitopes important for both colonisation and disease progression	1664:1765	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	0	46	theme	toxin	36:40	arg1	fragments					42:50	Apx toxin fragments	32:50	Apx toxin fragments	32:50	Cytoplasmic glycoengineering of Apx toxin fragments in the development of Actinobacillus pleuropneumoniae glycoconjugate vaccines.
30606265	7	47	theme	potential	1065:1073	arg1	targets					1075:1081	potential targets	1065:1081	potential targets for the basis of a vaccine against A. pleuropneumoniae infection	1065:1146	Both the toxins and glycosylation system represent potential targets for the basis of a vaccine against A. pleuropneumoniae infection.
30606265	11	48	theme	generating	1691:1700	arg1	epitopes					1702:1709	generating epitopes	1691:1709	generating epitopes important for both colonisation and disease progression	1691:1765	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	4	49	with	operon	649:654	arg1	agt					696:698	agt	696:698	agt	696:698	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	4	49	with	operon	649:654	arg1	transferase					683:693	a subsequent glycosyl transferase	661:693	a subsequent glycosyl transferase	661:693	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	3	50	theme	high	504:507	arg1	adhesins					526:533	high molecular weight adhesins	504:533	high molecular weight adhesins with glucose residues	504:555	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	3	51	theme	cytoplasmic	433:443	arg1	pleuropneumoniae					401:416	A. pleuropneumoniae	398:416	A. pleuropneumoniae	398:416	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	3	51	theme	cytoplasmic	433:443	arg1	system					461:466	a cytoplasmic N-glycosylation system	431:466	a cytoplasmic N-glycosylation system	431:466	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	6	52	theme	glucose	941:947	arg1	polymer					949:955	such a glucose polymer	934:955	such a glucose polymer	934:955	However to date, there is little evidence to suggest that such a glucose polymer is formed on its target peptides in A. pleuropneumoniae.
30606265	5	53	theme	recombinant	715:725	arg1	expression					727:736	Plasmid-borne recombinant expression	701:736	Plasmid-borne recombinant expression of these genes in E. coli	701:762	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	11	54	theme	novel	1673:1677	arg1	approach					1679:1686	a novel approach	1671:1686	a novel approach to generating epitopes important for both colonisation and disease progression	1671:1765	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	1	55	theme	Actinobacillus	142:155	arg1	agent					191:195	the causative agent	177:195	the causative agent of porcine pleuropneumonia	177:222	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	1	55	theme	Actinobacillus	142:155	arg1	pleuropneumoniae					157:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	3	56	theme	N-glycosylation	445:459	arg1	pleuropneumoniae					401:416	A. pleuropneumoniae	398:416	A. pleuropneumoniae	398:416	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	3	56	theme	N-glycosylation	445:459	arg1	system					461:466	a cytoplasmic N-glycosylation system	431:466	a cytoplasmic N-glycosylation system	431:466	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	4	57	theme	soluble	589:595	arg1	transferase					608:618	the soluble N-glycosyl transferase	585:618	the soluble N-glycosyl transferase	585:618	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	4	57	theme	soluble	589:595	arg1	Central					558:564	Central	558:564	Central	558:564	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	4	57	theme	soluble	589:595	arg1	ngt					621:623	ngt	621:623	ngt	621:623	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	10	58	theme	toxin	1521:1525	arg1	fragments					1527:1535	toxin fragments	1521:1535	toxin fragments	1521:1535	A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.
30606265	8	59	dep	RESULTS	1149:1155	arg1	developed					1175:1183	developed	1175:1183	developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose	1175:1315	RESULTS In this study, we developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose.
30606265	5	60	contain	containing	823:832	arg2	NX					867:868	NX	867:868	NX(S/T)	867:873	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	5	60	contain	containing	823:832	arg2	sequon					859:864	the appropriate acceptor sequon	834:864	the appropriate acceptor sequon	834:864	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	5	60	contain	containing	823:832	arg1	peptides					814:821	peptides	814:821	peptides containing the appropriate acceptor sequon, NX(S/T)	814:873	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
30606265	11	61	theme	vaccine	1593:1599	arg1	candidate					1601:1609	A vaccine candidate	1591:1609	A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression	1591:1765	CONCLUSIONS A vaccine candidate that combines toxin fragment with a conserved glycan offers a novel approach to generating epitopes important for both colonisation and disease progression.
30606265	3	62	theme	adhesins	526:533	arg1	modification					488:499	the modification	484:499	the modification of high molecular weight adhesins with glucose residues	484:555	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	1	63	theme	livestock	261:269	arg1	industry					271:278	the livestock industry	257:278	the livestock industry	257:278	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	10	64	theme	fragments	1527:1535	arg1	glucosylation					1504:1516	the glucosylation	1500:1516	the glucosylation of toxin fragments by a short glycan, rather than a polymer	1500:1576	A single chromosomal copy of ngt and agt resulted in the glucosylation of toxin fragments by a short glycan, rather than a polymer.
30606265	2	65	theme	toxins	360:365	arg1	series					339:344	a series	337:344	a series of haemolytic toxins	337:365	Virulence can largely be attributed to the secretion of a series of haemolytic toxins, which are highly immunogenic.
30606265	9	66	theme	native-like	1406:1416	arg1	operon					1418:1423	a native-like operon	1404:1423	a native-like operon for glycoengineering	1404:1444	We transferred ngt and agt to the chromosome of Escherichia coli in order to generate a native-like operon for glycoengineering.
30606265	4	67	theme	glycosyl	674:681	arg1	agt					696:698	agt	696:698	agt	696:698	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	4	67	theme	glycosyl	674:681	arg1	transferase					683:693	a subsequent glycosyl transferase	661:693	a subsequent glycosyl transferase	661:693	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	3	68	theme	molecular	509:517	arg1	adhesins					526:533	high molecular weight adhesins	504:533	high molecular weight adhesins with glucose residues	504:555	A. pleuropneumoniae also encodes a cytoplasmic N-glycosylation system, which involves the modification of high molecular weight adhesins with glucose residues.
30606265	1	69	theme	causative	181:189	arg1	agent					191:195	the causative agent	177:195	the causative agent of porcine pleuropneumonia	177:222	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	1	69	theme	causative	181:189	arg1	pleuropneumoniae					157:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae	131:172	BACKGROUND Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and represents a major burden to the livestock industry.
30606265	4	70	theme	subsequent	663:672	arg1	agt					696:698	agt	696:698	agt	696:698	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	4	70	theme	subsequent	663:672	arg1	transferase					683:693	a subsequent glycosyl transferase	661:693	a subsequent glycosyl transferase	661:693	Central to this process is the soluble N-glycosyl transferase, ngt, which is encoded in an operon with a subsequent glycosyl transferase, agt.
30606265	8	71	theme	cytoplasmic	1185:1195	arg1	glycoengineering					1197:1212	cytoplasmic glycoengineering	1185:1212	cytoplasmic glycoengineering	1185:1212	RESULTS In this study, we developed cytoplasmic glycoengineering to construct glycoconjugate vaccine candidates composed of soluble toxin fragments modified by glucose.
30606265	5	72	from	expression	727:736	arg1	coli					759:762	E. coli	756:762	E. coli	756:762	Plasmid-borne recombinant expression of these genes in E. coli results in the production of a glucose polymer on peptides containing the appropriate acceptor sequon, NX(S/T).
31613894	6	0	theme	RPE1	882:885	arg1	BJ1					898:900	BJ1	898:900	BJ1	898:900	Cytotoxicity of DPP nanocapsules was evaluated against RPE1 cell line (BJ1).
31613894	6	0	theme	RPE1	882:885	arg1	line					892:895	RPE1 cell line	882:895	RPE1 cell line (BJ1)	882:901	Cytotoxicity of DPP nanocapsules was evaluated against RPE1 cell line (BJ1).
31613894	10	1	theme	symbiotic	1719:1727	arg1	product					1740:1746	a symbiotic functional product	1717:1746	a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms	1717:1830	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	7	2	theme	Fe	1049:1050	arg1	content					1038:1044	high content	1033:1044	high content of Fe	1033:1050	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	2	theme	Fe	1049:1050	arg1	content					970:976	its rich content	961:976	its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g)	961:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	3	theme	IC50	1319:1322	arg1	potentials					1307:1316	DPP antioxidant potentials	1291:1316	DPP antioxidant potentials (IC50 35.54 mg/g)	1291:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	3	theme	IC50	1319:1322	arg1	mg/g					1330:1333	IC50 35.54 mg/g	1319:1333	IC50 35.54 mg/g	1319:1333	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	9	4	theme	nanoencapsulated	1481:1496	arg1	DPP					1498:1500	nanoencapsulated DPP	1481:1500	nanoencapsulated DPP	1481:1500	Fortification with nanoencapsulated DPP proved to be safe and the recommended form due to the announced positive characteristics.
31613894	6	5	theme	nanocapsules	847:858	arg1	Cytotoxicity					827:838	Cytotoxicity	827:838	Cytotoxicity of DPP nanocapsules	827:858	Cytotoxicity of DPP nanocapsules was evaluated against RPE1 cell line (BJ1).
31613894	7	6	theme	DPP	1291:1293	arg1	potentials					1307:1316	DPP antioxidant potentials	1291:1316	DPP antioxidant potentials (IC50 35.54 mg/g)	1291:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	6	theme	DPP	1291:1293	arg1	mg/g					1330:1333	IC50 35.54 mg/g	1319:1333	IC50 35.54 mg/g	1319:1333	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	0	7	theme	fortified	126:134	arg1	yoghurt					136:142	fortified yoghurt	126:142	fortified yoghurt	126:142	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	10	8	theme	DPP	1619:1621	arg1	forms					1623:1627	DPP forms	1619:1627	DPP forms	1619:1627	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	1	9	theme	study	161:165	arg1	aim					149:151	The aim	145:151	The aim of this study	145:165	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	5	10	theme	Liquid	798:803	arg1	Chromatography					805:818	Gas Liquid Chromatography	794:818	Gas Liquid Chromatography (GLC)	794:824	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	5	10	theme	Liquid	798:803	arg1	GLC					821:823	GLC	821:823	GLC	821:823	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	9	11	theme	recommended	1528:1538	arg1	form					1540:1543	the recommended form	1524:1543	the recommended form	1524:1543	Fortification with nanoencapsulated DPP proved to be safe and the recommended form due to the announced positive characteristics.
31613894	7	12	theme	rich	965:968	arg1	Mg					1060:1061	Mg	1060:1061	Mg (226.5, 124.4 and 318 mg/100g)	1060:1092	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	12	theme	rich	965:968	arg1	content					1038:1044	high content	1033:1044	high content of Fe	1033:1050	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	12	theme	rich	965:968	arg1	acids					1113:1117	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds	1095:1230	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g)	1095:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	12	theme	rich	965:968	arg1	Zn					1053:1054	Zn	1053:1054	Zn	1053:1054	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	12	theme	rich	965:968	arg1	content					970:976	its rich content	961:976	its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g)	961:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	1	13	theme	Egyptian	183:190	arg1	grains					215:220	Egyptian date palm pollen (DPP) grains	183:220	Egyptian date palm pollen (DPP) grains composition	183:232	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	13	theme	Egyptian	183:190	arg1	DPP					210:212	DPP	210:212	DPP	210:212	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	7	14	theme	carbohydrate	993:1004	arg1	Mg					1060:1061	Mg	1060:1061	Mg (226.5, 124.4 and 318 mg/100g)	1060:1092	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	14	theme	carbohydrate	993:1004	arg1	content					1038:1044	high content	1033:1044	high content of Fe	1033:1050	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	14	theme	carbohydrate	993:1004	arg1	acids					1113:1117	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds	1095:1230	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g)	1095:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	14	theme	carbohydrate	993:1004	arg1	Zn					1053:1054	Zn	1053:1054	Zn	1053:1054	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	14	theme	carbohydrate	993:1004	arg1	content					970:976	its rich content	961:976	its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g)	961:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	3	15	theme	Scanning	545:552	arg1	SEM					575:577	SEM	575:577	SEM	575:577	The micro morphology was explored via Scanning Electron Microscope (SEM).
31613894	3	15	theme	Scanning	545:552	arg1	Microscope					563:572	Scanning Electron Microscope	545:572	Scanning Electron Microscope (SEM)	545:578	The micro morphology was explored via Scanning Electron Microscope (SEM).
31613894	7	16	theme	protein	981:987	arg1	Mg					1060:1061	Mg	1060:1061	Mg (226.5, 124.4 and 318 mg/100g)	1060:1092	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	16	theme	protein	981:987	arg1	content					1038:1044	high content	1033:1044	high content of Fe	1033:1050	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	16	theme	protein	981:987	arg1	acids					1113:1117	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds	1095:1230	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g)	1095:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	16	theme	protein	981:987	arg1	Zn					1053:1054	Zn	1053:1054	Zn	1053:1054	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	16	theme	protein	981:987	arg1	content					970:976	its rich content	961:976	its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g)	961:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	10	17	theme	Holding	1669:1675	arg1	WHC					1687:1689	WHC	1687:1689	WHC	1687:1689	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	10	17	theme	Holding	1669:1675	arg1	Capacity					1677:1684	Water Holding Capacity	1663:1684	Water Holding Capacity (WHC)	1663:1690	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	7	18	theme	grains	934:939	arg1	evaluation					941:950	The Egyptian date palm pollen grains evaluation	904:950	The Egyptian date palm pollen grains evaluation	904:950	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	9	19	theme	positive	1566:1573	arg1	characteristics					1575:1589	the announced positive characteristics	1552:1589	the announced positive characteristics	1552:1589	Fortification with nanoencapsulated DPP proved to be safe and the recommended form due to the announced positive characteristics.
31613894	0	20	from	impact	71:76	arg1	properties					112:121	the nutritional and functional properties	81:121	the nutritional and functional properties of fortified yoghurt	81:142	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	10	21	theme	DPP	1822:1824	arg1	forms					1826:1830	DPP forms	1822:1830	DPP forms	1822:1830	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	9	22	dep	form	1540:1543	arg1	characteristics					1575:1589	the announced positive characteristics	1552:1589	the announced positive characteristics	1552:1589	Fortification with nanoencapsulated DPP proved to be safe and the recommended form due to the announced positive characteristics.
31613894	7	23	theme	palm	922:925	arg1	grains					934:939	The Egyptian date palm pollen grains	904:939	The Egyptian date palm pollen grains evaluation	904:950	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	4	24	theme	groups	656:661	arg1	detection					663:671	functional groups detection	645:671	functional groups detection	645:671	Fourier Transform Infrared (FTIR) spectroscopy was employed for functional groups detection.
31613894	7	25	theme	unsaturated	1095:1105	arg1	content					970:976	its rich content	961:976	its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g)	961:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	25	theme	unsaturated	1095:1105	arg1	acids					1113:1117	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds	1095:1230	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g)	1095:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	26	theme	Egyptian	908:915	arg1	grains					934:939	The Egyptian date palm pollen grains	904:939	The Egyptian date palm pollen grains evaluation	904:950	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	10	27	with	fortification	1600:1612	arg1	forms					1623:1627	DPP forms	1619:1627	DPP forms	1619:1627	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	1	28	theme	%	301:301	arg1	extract					311:317	80% ethanol extract	299:317	80% ethanol extract	299:317	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	28	theme	%	301:301	arg1	forms					292:296	two forms	288:296	two forms; 80% ethanol extract, and nanoencapsulated form	288:344	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	5	29	theme	High	710:713	arg1	HPLC					750:753	HPLC	750:753	HPLC	750:753	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	5	29	theme	High	710:713	arg1	Chromatography					734:747	High Performance Liquid Chromatography	710:747	High Performance Liquid Chromatography (HPLC)	710:754	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	8	30	theme	amides	1389:1394	arg1	presence					1369:1376	the presence	1365:1376	the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP	1365:1459	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	5	31	theme	Performance	715:725	arg1	HPLC					750:753	HPLC	750:753	HPLC	750:753	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	5	31	theme	Performance	715:725	arg1	Chromatography					734:747	High Performance Liquid Chromatography	710:747	High Performance Liquid Chromatography (HPLC)	710:754	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	0	32	theme	date	14:17	arg1	palm					19:22	date palm	14:22	date palm	14:22	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	1	33	dep	forms	292:296	arg1	form					341:344	nanoencapsulated form	324:344	nanoencapsulated form	324:344	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	33	dep	forms	292:296	arg1	extract					311:317	80% ethanol extract	299:317	80% ethanol extract	299:317	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	33	dep	forms	292:296	arg1	forms					292:296	two forms	288:296	two forms; 80% ethanol extract, and nanoencapsulated form	288:344	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	0	34	dep	Phoenix	32:38	arg1	L.					52:53	Phoenix dactylifera L.	32:53	Phoenix dactylifera L.	32:53	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	5	35	theme	Liquid	727:732	arg1	HPLC					750:753	HPLC	750:753	HPLC	750:753	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	5	35	theme	Liquid	727:732	arg1	Chromatography					734:747	High Performance Liquid Chromatography	710:747	High Performance Liquid Chromatography (HPLC)	710:754	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	5	36	theme	fatty	762:766	arg1	acids					768:772	fatty acids	762:772	fatty acids	762:772	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	2	37	dep	physicochemical	423:437	arg1	characteristics					476:490	characteristics	476:490	characteristics	476:490	Functional yoghurt fortified with DPP in three forms was prepared and their physicochemical, microstructure, texture and sensory characteristics were assessed.
31613894	4	38	dep	Fourier	581:587	arg1	Transform					589:597	Transform	589:597	Transform Infrared (FTIR) spectroscopy	589:626	Fourier Transform Infrared (FTIR) spectroscopy was employed for functional groups detection.
31613894	4	39	dep	Infrared	599:606	arg1	FTIR					609:612	FTIR	609:612	FTIR	609:612	Fourier Transform Infrared (FTIR) spectroscopy was employed for functional groups detection.
31613894	1	40	theme	date	192:195	arg1	grains					215:220	Egyptian date palm pollen (DPP) grains	183:220	Egyptian date palm pollen (DPP) grains composition	183:232	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	40	theme	date	192:195	arg1	DPP					210:212	DPP	210:212	DPP	210:212	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	41	theme	pollen	202:207	arg1	grains					215:220	Egyptian date palm pollen (DPP) grains	183:220	Egyptian date palm pollen (DPP) grains composition	183:232	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	41	theme	pollen	202:207	arg1	DPP					210:212	DPP	210:212	DPP	210:212	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	7	42	theme	35.54	1324:1328	arg1	potentials					1307:1316	DPP antioxidant potentials	1291:1316	DPP antioxidant potentials (IC50 35.54 mg/g)	1291:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	42	theme	35.54	1324:1328	arg1	mg/g					1330:1333	IC50 35.54 mg/g	1319:1333	IC50 35.54 mg/g	1319:1333	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	10	43	theme	functional	1729:1738	arg1	product					1740:1746	a symbiotic functional product	1717:1746	a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms	1717:1830	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	9	44	with	Fortification	1462:1474	arg1	DPP					1498:1500	nanoencapsulated DPP	1481:1500	nanoencapsulated DPP	1481:1500	Fortification with nanoencapsulated DPP proved to be safe and the recommended form due to the announced positive characteristics.
31613894	7	45	theme	high	1033:1036	arg1	content					1038:1044	high content	1033:1044	high content of Fe	1033:1050	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	45	theme	high	1033:1036	arg1	content					970:976	its rich content	961:976	its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g)	961:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	10	46	theme	Yoghurt	1592:1598	arg1	fortification					1600:1612	Yoghurt fortification	1592:1612	Yoghurt fortification with DPP forms	1592:1627	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	1	47	theme	grains	215:220	arg1	potentials					259:268	potentials	259:268	physical and functional potentials	235:268	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	47	theme	grains	215:220	arg1	composition					222:232	Egyptian date palm pollen (DPP) grains composition	183:232	Egyptian date palm pollen (DPP) grains composition	183:232	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	7	48	theme	antioxidant	1295:1305	arg1	potentials					1307:1316	DPP antioxidant potentials	1291:1316	DPP antioxidant potentials (IC50 35.54 mg/g)	1291:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	48	theme	antioxidant	1295:1305	arg1	mg/g					1330:1333	IC50 35.54 mg/g	1319:1333	IC50 35.54 mg/g	1319:1333	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	6	49	theme	DPP	843:845	arg1	nanocapsules					847:858	DPP nanocapsules	843:858	DPP nanocapsules	843:858	Cytotoxicity of DPP nanocapsules was evaluated against RPE1 cell line (BJ1).
31613894	10	50	dep	product	1740:1746	arg1	contained					1754:1762	contained	1754:1762	contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms	1754:1830	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	7	51	theme	g/	1023:1024	arg1	carbohydrate					993:1004	carbohydrate	993:1004	carbohydrate (36.28 and 17.14 g/ 100g)	993:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	51	theme	g/	1023:1024	arg1	100g					1026:1029	36.28 and 17.14 g/ 100g	1007:1029	36.28 and 17.14 g/ 100g	1007:1029	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	0	52	theme	functional	101:110	arg1	properties					112:121	the nutritional and functional properties	81:121	the nutritional and functional properties of fortified yoghurt	81:142	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	0	53	dep	pollen	24:29	arg1	Phoenix					32:38	Phoenix	32:38	Phoenix	32:38	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	3	54	theme	micro	511:515	arg1	morphology					517:526	The micro morphology	507:526	The micro morphology	507:526	The micro morphology was explored via Scanning Electron Microscope (SEM).
31613894	5	55	theme	Gas	794:796	arg1	Chromatography					805:818	Gas Liquid Chromatography	794:818	Gas Liquid Chromatography (GLC)	794:824	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	5	55	theme	Gas	794:796	arg1	GLC					821:823	GLC	821:823	GLC	821:823	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	7	56	from	potentials	1307:1316	arg1	pronounced					1277:1286	pronounced	1277:1286	pronounced	1277:1286	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	10	57	contain	contained	1754:1762	arg1	it					1751:1752	it	1751:1752	it	1751:1752	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	10	57	contain	contained	1754:1762	arg2	prebiotics					1796:1805	prebiotics	1796:1805	prebiotics represented in DPP forms	1796:1830	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	10	57	contain	contained	1754:1762	arg2	CFU/g					1785:1789	106 CFU/g	1781:1789	106 CFU/g	1781:1789	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	10	57	contain	contained	1754:1762	arg2	probiotics					1769:1778	both probiotics	1764:1778	both probiotics (106 CFU/g)	1764:1790	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	10	58	dep	enhanced	1629:1636	arg1	considered					1706:1715	considered	1706:1715	can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms	1699:1830	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	5	59	theme	Phenolic	674:681	arg1	compounds					683:691	Phenolic compounds	674:691	Phenolic compounds	674:691	Phenolic compounds were detected by High Performance Liquid Chromatography (HPLC) while fatty acids were identified via Gas Liquid Chromatography (GLC).
31613894	1	60	theme	nanoencapsulated	324:339	arg1	form					341:344	nanoencapsulated form	324:344	nanoencapsulated form	324:344	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	60	theme	nanoencapsulated	324:339	arg1	forms					292:296	two forms	288:296	two forms; 80% ethanol extract, and nanoencapsulated form	288:344	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	3	61	theme	Electron	554:561	arg1	SEM					575:577	SEM	575:577	SEM	575:577	The micro morphology was explored via Scanning Electron Microscope (SEM).
31613894	3	61	theme	Electron	554:561	arg1	Microscope					563:572	Scanning Electron Microscope	545:572	Scanning Electron Microscope (SEM)	545:578	The micro morphology was explored via Scanning Electron Microscope (SEM).
31613894	8	62	attach	presence	1369:1376	arg2	polysaccharides					1411:1425	polysaccharides	1411:1425	polysaccharides (fibers)	1411:1434	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	8	62	attach	presence	1369:1376	arg1	DPP					1457:1459	DPP	1457:1459	DPP	1457:1459	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	8	62	attach	presence	1369:1376	arg2	proteins					1397:1404	proteins	1397:1404	proteins	1397:1404	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	8	62	attach	presence	1369:1376	arg2	fibers					1428:1433	fibers	1428:1433	fibers	1428:1433	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	8	62	attach	presence	1369:1376	arg2	amides					1389:1394	soluble amides	1381:1394	soluble amides (proteins)	1381:1405	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	4	63	theme	Infrared	599:606	arg1	spectroscopy					615:626	Infrared (FTIR) spectroscopy	599:626	Infrared (FTIR) spectroscopy	599:626	Fourier Transform Infrared (FTIR) spectroscopy was employed for functional groups detection.
31613894	0	64	theme	yoghurt	136:142	arg1	properties					112:121	the nutritional and functional properties	81:121	the nutritional and functional properties of fortified yoghurt	81:142	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	7	65	theme	phenolic	1213:1220	arg1	compounds					1222:1230	phenolic compounds	1213:1230	phenolic compounds	1213:1230	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	8	66	dep	amides	1389:1394	arg1	groups					1447:1452	functional groups	1436:1452	functional groups	1436:1452	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	9	67	theme	announced	1556:1564	arg1	characteristics					1575:1589	the announced positive characteristics	1552:1589	the announced positive characteristics	1552:1589	Fortification with nanoencapsulated DPP proved to be safe and the recommended form due to the announced positive characteristics.
31613894	7	68	theme	fatty	1107:1111	arg1	content					970:976	its rich content	961:976	its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g)	961:1030	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	68	theme	fatty	1107:1111	arg1	acids					1113:1117	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds	1095:1230	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g)	1095:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	10	69	theme	Water	1663:1667	arg1	WHC					1687:1689	WHC	1687:1689	WHC	1687:1689	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	10	69	theme	Water	1663:1667	arg1	Capacity					1677:1684	Water Holding Capacity	1663:1684	Water Holding Capacity (WHC)	1663:1690	Yoghurt fortification with DPP forms enhanced viscosity, syneresis and Water Holding Capacity (WHC), which can be considered a symbiotic functional product as it contained both probiotics (106 CFU/g) and prebiotics represented in DPP forms.
31613894	7	70	theme	ethanol	1189:1195	arg1	extraction					1197:1206	ethanol extraction	1189:1206	ethanol extraction	1189:1206	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	71	theme	pollen	927:932	arg1	grains					934:939	The Egyptian date palm pollen grains	904:939	The Egyptian date palm pollen grains evaluation	904:950	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	8	72	theme	FTIR	1341:1344	arg1	analyses					1346:1353	The FTIR analyses	1337:1353	The FTIR analyses	1337:1353	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	4	73	theme	functional	645:654	arg1	detection					663:671	functional groups detection	645:671	functional groups detection	645:671	Fourier Transform Infrared (FTIR) spectroscopy was employed for functional groups detection.
31613894	1	74	theme	80	299:300	arg1	%					301:301	%	301:301	%	301:301	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	7	75	theme	date	917:920	arg1	grains					934:939	The Egyptian date palm pollen grains	904:939	The Egyptian date palm pollen grains evaluation	904:950	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	76	from	pronounced	1277:1286	arg1	potentials					1307:1316	DPP antioxidant potentials	1291:1316	DPP antioxidant potentials (IC50 35.54 mg/g)	1291:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	76	from	pronounced	1277:1286	arg1	mg/g					1330:1333	IC50 35.54 mg/g	1319:1333	IC50 35.54 mg/g	1319:1333	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	0	77	theme	nutritional	85:95	arg1	properties					112:121	the nutritional and functional properties	81:121	the nutritional and functional properties of fortified yoghurt	81:142	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	1	78	theme	ethanol	303:309	arg1	extract					311:317	80% ethanol extract	299:317	80% ethanol extract	299:317	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	78	theme	ethanol	303:309	arg1	forms					292:296	two forms	288:296	two forms; 80% ethanol extract, and nanoencapsulated form	288:344	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	7	79	dep	ω-3	1119:1121	arg1	g/100g					1158:1163	8.76, 20.26 and 7.11 g/100g	1137:1163	8.76, 20.26 and 7.11 g/100g	1137:1163	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	8	80	theme	soluble	1381:1387	arg1	amides					1389:1394	soluble amides	1381:1394	soluble amides (proteins)	1381:1405	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	8	80	theme	soluble	1381:1387	arg1	proteins					1397:1404	proteins	1397:1404	proteins	1397:1404	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	0	81	theme	palm	19:22	arg1	Evaluation					0:9	Evaluation	0:9	Evaluation of date palm	0:22	Evaluation of date palm pollen (Phoenix dactylifera L.) encapsulation, impact on the nutritional and functional properties of fortified yoghurt.
31613894	1	82	theme	physical	235:242	arg1	potentials					259:268	potentials	259:268	physical and functional potentials	235:268	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	82	theme	physical	235:242	arg1	composition					222:232	Egyptian date palm pollen (DPP) grains composition	183:232	Egyptian date palm pollen (DPP) grains composition	183:232	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	8	83	from	presence	1369:1376	arg1	DPP					1457:1459	DPP	1457:1459	DPP	1457:1459	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	1	84	theme	functional	248:257	arg1	potentials					259:268	potentials	259:268	physical and functional potentials	235:268	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	84	theme	functional	248:257	arg1	composition					222:232	Egyptian date palm pollen (DPP) grains composition	183:232	Egyptian date palm pollen (DPP) grains composition	183:232	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	7	85	dep	acids	1113:1117	arg1	catechin					1243:1250	catechin	1243:1250	unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g)	1095:1334	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	85	dep	acids	1113:1117	arg1	μg/mL					1260:1264	191.73 μg/mL	1253:1264	191.73 μg/mL	1253:1264	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	85	dep	acids	1113:1117	arg1	compounds					1222:1230	phenolic compounds	1213:1230	phenolic compounds	1213:1230	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	85	dep	acids	1113:1117	arg1	ω-3					1119:1121	ω-3	1119:1121	ω-3	1119:1121	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	7	85	dep	acids	1113:1117	arg1	ω-9					1132:1134	ω-9	1132:1134	ω-9	1132:1134	The Egyptian date palm pollen grains evaluation revealed its rich content of protein and carbohydrate (36.28 and 17.14 g/ 100g), high content of Fe, Zn and Mg (226.5, 124.4 and 318 mg/100g), unsaturated fatty acids ω-3, ω-6 and ω-9 (8.76, 20.26 and 7.11 g/100g, which was increased by ethanol extraction) and phenolic compounds especially catechin (191.73 μg/mL) which was pronounced in DPP antioxidant potentials (IC50 35.54 mg/g).
31613894	2	86	theme	Functional	347:356	arg1	yoghurt					358:364	Functional yoghurt	347:364	Functional yoghurt fortified with DPP in three forms	347:398	Functional yoghurt fortified with DPP in three forms was prepared and their physicochemical, microstructure, texture and sensory characteristics were assessed.
31613894	8	87	theme	polysaccharides	1411:1425	arg1	presence					1369:1376	the presence	1365:1376	the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP	1365:1459	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31613894	6	88	theme	cell	887:890	arg1	BJ1					898:900	BJ1	898:900	BJ1	898:900	Cytotoxicity of DPP nanocapsules was evaluated against RPE1 cell line (BJ1).
31613894	6	88	theme	cell	887:890	arg1	line					892:895	RPE1 cell line	882:895	RPE1 cell line (BJ1)	882:901	Cytotoxicity of DPP nanocapsules was evaluated against RPE1 cell line (BJ1).
31613894	1	89	theme	palm	197:200	arg1	grains					215:220	Egyptian date palm pollen (DPP) grains	183:220	Egyptian date palm pollen (DPP) grains composition	183:232	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	1	89	theme	palm	197:200	arg1	DPP					210:212	DPP	210:212	DPP	210:212	The aim of this study was to evaluate Egyptian date palm pollen (DPP) grains composition, physical and functional potentials in comparing with two forms; 80% ethanol extract, and nanoencapsulated form.
31613894	8	90	theme	functional	1436:1445	arg1	groups					1447:1452	functional groups	1436:1452	functional groups	1436:1452	The FTIR analyses indicated the presence of soluble amides (proteins) and polysaccharides (fibers) functional groups in DPP.
31665542	6	0	theme	glycosylation	959:971	arg1	tunicamycin					984:994	tunicamycin	984:994	tunicamycin	984:994	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	6	0	theme	glycosylation	959:971	arg1	inhibitor					973:981	An N-linked glycosylation inhibitor	947:981	An N-linked glycosylation inhibitor	947:981	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	1	1	theme	higher	163:168	arg1	temperatures					170:181	higher temperatures	163:181	higher temperatures	163:181	Adaptation to higher temperatures would increase the environmental competitiveness of psychrophiles, organisms that thrive in low-temperature environments.
31665542	1	2	theme	low-temperature	275:289	arg1	environments					291:302	low-temperature environments	275:302	low-temperature environments	275:302	Adaptation to higher temperatures would increase the environmental competitiveness of psychrophiles, organisms that thrive in low-temperature environments.
31665542	6	3	theme	N-linked	950:957	arg1	tunicamycin					984:994	tunicamycin	984:994	tunicamycin	984:994	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	6	3	theme	N-linked	950:957	arg1	inhibitor					973:981	An N-linked glycosylation inhibitor	947:981	An N-linked glycosylation inhibitor	947:981	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	3	4	theme	S-layer	541:547	arg1	proteins					549:556	S-layer proteins	541:556	S-layer proteins	541:556	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	2	5	theme	cold	335:338	arg1	methanogen					348:357	a cold wetland methanogen	333:357	a cold wetland methanogen	333:357	Methanolobus psychrophilus, a cold wetland methanogen, 'evolved' as a mesophile, growing optimally at 30 °C after subculturings, and cells grown with ample substrates exhibited higher integrity.
31665542	2	5	theme	cold	335:338	arg1	psychrophilus					318:330	Methanolobus psychrophilus	305:330	Methanolobus psychrophilus	305:330	Methanolobus psychrophilus, a cold wetland methanogen, 'evolved' as a mesophile, growing optimally at 30 °C after subculturings, and cells grown with ample substrates exhibited higher integrity.
31665542	6	6	theme	growth	1043:1048	arg1	levels					1019:1024	glycosylation levels	1005:1024	glycosylation levels of Mpsy_1486 and growth	1005:1048	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	4	7	theme	protein	773:779	arg1	Mpsy_1486					781:789	the S-layer protein Mpsy_1486	761:789	the S-layer protein Mpsy_1486	761:789	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	4	7	theme	protein	773:779	arg1	glycoprotein					664:675	a glycoprotein	662:675	a glycoprotein	662:675	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	3	8	theme	envelope	578:585	arg1	N-glycosylation					522:536	N-glycosylation	522:536	N-glycosylation of S-layer proteins	522:556	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	3	8	theme	envelope	578:585	arg1	component					587:595	the major archaeal envelope component	559:595	the major archaeal envelope component	559:595	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	4	9	gly	glycoprotein	664:675	arg1	Mpsy_1486					781:789	the S-layer protein Mpsy_1486	761:789	the S-layer protein Mpsy_1486	761:789	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	4	9	gly	glycoprotein	664:675	arg1	glycoprotein					664:675	a glycoprotein	662:675	a glycoprotein	662:675	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	6	10	theme	temperature	1134:1144	arg1	adaptation					1146:1155	higher temperature adaptation	1127:1155	higher temperature adaptation	1127:1155	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	6	11	link	N-linked	950:957	arg1	tunicamycin					984:994	tunicamycin	984:994	tunicamycin	984:994	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	6	11	link	N-linked	950:957	arg1	inhibitor					973:981	An N-linked glycosylation inhibitor	947:981	An N-linked glycosylation inhibitor	947:981	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	0	12	theme	elevated	103:110	arg1	temperatures					112:123	elevated temperatures	103:123	elevated temperatures in abundant substrates	103:146	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	3	13	theme	major	563:567	arg1	N-glycosylation					522:536	N-glycosylation	522:536	N-glycosylation of S-layer proteins	522:556	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	3	13	theme	major	563:567	arg1	component					587:595	the major archaeal envelope component	559:595	the major archaeal envelope component	559:595	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	6	14	theme	higher	1127:1132	arg1	adaptation					1146:1155	higher temperature adaptation	1127:1155	higher temperature adaptation	1127:1155	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	3	15	gly	N-glycosylation	522:536	arg1	proteins					549:556	S-layer proteins	541:556	S-layer proteins	541:556	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	4	16	theme	ample	707:711	arg1	availability					723:734	ample substrate availability	707:734	ample substrate availability	707:734	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	0	17	theme	Enhanced	0:7	arg1	glycosylation					9:21	Enhanced glycosylation	0:21	Enhanced glycosylation of an S-layer protein	0:43	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	6	18	theme	Mpsy_1486	1029:1037	arg1	levels					1019:1024	glycosylation levels	1005:1024	glycosylation levels of Mpsy_1486 and growth	1005:1048	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	4	19	theme	S-layer	765:771	arg1	Mpsy_1486					781:789	the S-layer protein Mpsy_1486	761:789	the S-layer protein Mpsy_1486	761:789	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	4	19	theme	S-layer	765:771	arg1	glycoprotein					664:675	a glycoprotein	662:675	a glycoprotein	662:675	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	1	20	theme	environmental	202:214	arg1	competitiveness					216:230	the environmental competitiveness	198:230	the environmental competitiveness of psychrophiles, organisms that thrive in low-temperature environments	198:302	Adaptation to higher temperatures would increase the environmental competitiveness of psychrophiles, organisms that thrive in low-temperature environments.
31665542	2	21	theme	ample	455:459	arg1	substrates					461:470	ample substrates	455:470	ample substrates	455:470	Methanolobus psychrophilus, a cold wetland methanogen, 'evolved' as a mesophile, growing optimally at 30 °C after subculturings, and cells grown with ample substrates exhibited higher integrity.
31665542	0	22	theme	abundant	128:135	arg1	substrates					137:146	abundant substrates	128:146	abundant substrates	128:146	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	6	23	theme	protein	1101:1107	arg1	glycosylation					1109:1121	S-layer protein glycosylation	1093:1121	S-layer protein glycosylation	1093:1121	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	5	24	theme	glycosylation	875:887	arg1	profiles					889:896	different glycosylation profiles	865:896	different glycosylation profiles	865:896	Four N-glycosylation sites were identified on Mpsy_1486, which exhibited different glycosylation profiles, with N94 only found in cells cultured at 30 °C.
31665542	5	25	located	found	913:917	arg2	N94					904:906	N94	904:906	N94 only found in cells cultured at 30 °C	904:944	Four N-glycosylation sites were identified on Mpsy_1486, which exhibited different glycosylation profiles, with N94 only found in cells cultured at 30 °C.
31665542	5	25	located	found	913:917	arg1	cells					922:926	cells	922:926	cells cultured at 30 °C	922:944	Four N-glycosylation sites were identified on Mpsy_1486, which exhibited different glycosylation profiles, with N94 only found in cells cultured at 30 °C.
31665542	2	26	theme	wetland	340:346	arg1	methanogen					348:357	a cold wetland methanogen	333:357	a cold wetland methanogen	333:357	Methanolobus psychrophilus, a cold wetland methanogen, 'evolved' as a mesophile, growing optimally at 30 °C after subculturings, and cells grown with ample substrates exhibited higher integrity.
31665542	2	26	theme	wetland	340:346	arg1	psychrophilus					318:330	Methanolobus psychrophilus	305:330	Methanolobus psychrophilus	305:330	Methanolobus psychrophilus, a cold wetland methanogen, 'evolved' as a mesophile, growing optimally at 30 °C after subculturings, and cells grown with ample substrates exhibited higher integrity.
31665542	6	27	theme	S-layer	1093:1099	arg1	glycosylation					1109:1121	S-layer protein glycosylation	1093:1121	S-layer protein glycosylation	1093:1121	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	0	28	theme	protein	37:43	arg1	glycosylation					9:21	Enhanced glycosylation	0:21	Enhanced glycosylation of an S-layer protein	0:43	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	6	29	theme	glycosylation	1005:1017	arg1	levels					1019:1024	glycosylation levels	1005:1024	glycosylation levels of Mpsy_1486 and growth	1005:1048	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	4	30	from	glycoprotein	664:675	arg1	cells					680:684	cells	680:684	cells grown at 30 °C under ample substrate availability	680:734	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	1	31	theme	psychrophiles	235:247	arg1	competitiveness					216:230	the environmental competitiveness	198:230	the environmental competitiveness of psychrophiles, organisms that thrive in low-temperature environments	198:302	Adaptation to higher temperatures would increase the environmental competitiveness of psychrophiles, organisms that thrive in low-temperature environments.
31665542	0	32	theme	S-layer	29:35	arg1	protein					37:43	an S-layer protein	26:43	an S-layer protein	26:43	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	0	33	gly	glycosylation	9:21	arg1	protein					37:43	an S-layer protein	26:43	an S-layer protein	26:43	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	5	34	theme	different	865:873	arg1	profiles					889:896	different glycosylation profiles	865:896	different glycosylation profiles	865:896	Four N-glycosylation sites were identified on Mpsy_1486, which exhibited different glycosylation profiles, with N94 only found in cells cultured at 30 °C.
31665542	5	35	theme	N-glycosylation	797:811	arg1	sites					813:817	Four N-glycosylation sites	792:817	Four N-glycosylation sites	792:817	Four N-glycosylation sites were identified on Mpsy_1486, which exhibited different glycosylation profiles, with N94 only found in cells cultured at 30 °C.
31665542	6	36	theme	psychrophilic	1164:1176	arg1	M. psychrophilus					1187:1202	the psychrophilic archaeon M. psychrophilus	1160:1202	the psychrophilic archaeon M. psychrophilus	1160:1202	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	2	37	theme	higher	482:487	arg1	integrity					489:497	higher integrity	482:497	higher integrity	482:497	Methanolobus psychrophilus, a cold wetland methanogen, 'evolved' as a mesophile, growing optimally at 30 °C after subculturings, and cells grown with ample substrates exhibited higher integrity.
31665542	0	38	from	temperatures	112:123	arg1	substrates					137:146	abundant substrates	128:146	abundant substrates	128:146	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	3	39	theme	mesophilic	614:623	arg1	adaptation					625:634	mesophilic adaptation	614:634	mesophilic adaptation	614:634	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	6	40	gly	glycosylation	1109:1121	arg1	M. psychrophilus					1187:1202	the psychrophilic archaeon M. psychrophilus	1160:1202	the psychrophilic archaeon M. psychrophilus	1160:1202	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	6	41	theme	M. psychrophilus	1187:1202	arg1	adaptation					1146:1155	higher temperature adaptation	1127:1155	higher temperature adaptation	1127:1155	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	6	41	theme	M. psychrophilus	1187:1202	arg1	glycosylation					1109:1121	S-layer protein glycosylation	1093:1121	S-layer protein glycosylation	1093:1121	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	5	42	gly	N-glycosylation	797:811	arg2	sites					813:817	Four N-glycosylation sites	792:817	Four N-glycosylation sites	792:817	Four N-glycosylation sites were identified on Mpsy_1486, which exhibited different glycosylation profiles, with N94 only found in cells cultured at 30 °C.
31665542	5	42	gly	N-glycosylation	797:811	arg2	Four					792:795	Four	792:795	Four	792:795	Four N-glycosylation sites were identified on Mpsy_1486, which exhibited different glycosylation profiles, with N94 only found in cells cultured at 30 °C.
31665542	3	43	theme	archaeal	569:576	arg1	N-glycosylation					522:536	N-glycosylation	522:536	N-glycosylation of S-layer proteins	522:556	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	3	43	theme	archaeal	569:576	arg1	component					587:595	the major archaeal envelope component	559:595	the major archaeal envelope component	559:595	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	6	44	theme	archaeon	1178:1185	arg1	M. psychrophilus					1187:1202	the psychrophilic archaeon M. psychrophilus	1160:1202	the psychrophilic archaeon M. psychrophilus	1160:1202	An N-linked glycosylation inhibitor, tunicamycin, reduced glycosylation levels of Mpsy_1486 and growth at 30 °C, thus establishing a link between S-layer protein glycosylation and higher temperature adaptation of the psychrophilic archaeon M. psychrophilus.
31665542	4	45	theme	Lectin	637:642	arg1	affinity					644:651	Lectin affinity	637:651	Lectin affinity	637:651	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
31665542	0	46	theme	methanogenic	69:80	arg1	archaeon					82:89	a psychrophilic methanogenic archaeon	53:89	a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates	53:146	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	3	47	theme	proteins	549:556	arg1	N-glycosylation					522:536	N-glycosylation	522:536	N-glycosylation of S-layer proteins	522:556	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	3	47	theme	proteins	549:556	arg1	component					587:595	the major archaeal envelope component	559:595	the major archaeal envelope component	559:595	Here, we investigated N-glycosylation of S-layer proteins, the major archaeal envelope component, with respect to mesophilic adaptation.
31665542	0	48	theme	psychrophilic	55:67	arg1	archaeon					82:89	a psychrophilic methanogenic archaeon	53:89	a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates	53:146	Enhanced glycosylation of an S-layer protein enables a psychrophilic methanogenic archaeon to adapt to elevated temperatures in abundant substrates.
31665542	4	49	theme	substrate	713:721	arg1	availability					723:734	ample substrate availability	707:734	ample substrate availability	707:734	Lectin affinity enriched a glycoprotein in cells grown at 30 °C under ample substrate availability, which was identified as the S-layer protein Mpsy_1486.
30986068	5	0	theme	injury	940:945	arg1	evidence					919:926	no histopathological evidence	898:926	no histopathological evidence of vascular injury	898:945	A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathological evidence of vascular injury.
30986068	1	1	theme	AKT	252:254	arg1	overactive					267:276	overactive	267:276	overactive	267:276	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	1	1	theme	AKT	252:254	arg1	pathway					256:262	the AKT pathway	248:262	the AKT pathway	248:262	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	2	2	theme	purine	281:286	arg1	inhibitor					294:302	A purine PI3Kδ inhibitor	279:302	A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif	279:345	A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury.
30986068	4	3	theme	O-	629:630	arg1	identification					611:624	the identification	607:624	the identification of O- and N-linked heterocycloalkyls	607:661	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
30986068	1	4	theme	cell	135:138	arg1	activation					140:149	immune cell activation	128:149	immune cell activation	128:149	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	3	5	theme	benzimidazolone-piperidine	531:556	arg1	motif					570:574	the benzimidazolone-piperidine selectivity motif	527:574	the benzimidazolone-piperidine selectivity motif	527:574	Several strategies were implemented to mitigate this finding, including reconstruction of the benzimidazolone-piperidine selectivity motif.
30986068	5	6	theme	dog	829:831	arg1	study					846:850	a dog tolerability study	827:850	a dog tolerability study where it was found to be well tolerated	827:890	A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathological evidence of vascular injury.
30986068	3	7	theme	selectivity	558:568	arg1	motif					570:574	the benzimidazolone-piperidine selectivity motif	527:574	the benzimidazolone-piperidine selectivity motif	527:574	Several strategies were implemented to mitigate this finding, including reconstruction of the benzimidazolone-piperidine selectivity motif.
30986068	3	8	theme	Several	437:443	arg1	strategies					445:454	Several strategies	437:454	Several strategies	437:454	Several strategies were implemented to mitigate this finding, including reconstruction of the benzimidazolone-piperidine selectivity motif.
30986068	1	9	from	overactive	267:276	arg1	malignancies					226:237	hematological malignancies	212:237	inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive	179:276	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	1	10	theme	PI3Kδ	87:91	arg1	activity					103:110	PI3Kδ catalytic activity	87:110	PI3Kδ catalytic activity	87:110	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	5	11	theme	histopathological	901:917	arg1	evidence					919:926	no histopathological evidence	898:926	no histopathological evidence of vascular injury	898:945	A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathological evidence of vascular injury.
30986068	0	12	theme	Structure	0:8	arg1	Overhaul					10:17	Structure Overhaul	0:17	Structure Overhaul	0:17	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability.
30986068	4	13	theme	safety	763:768	arg1	profile					783:789	an improved safety pharmacology profile	751:789	an improved safety pharmacology profile	751:789	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
30986068	1	14	theme	catalytic	93:101	arg1	activity					103:110	PI3Kδ catalytic activity	87:110	PI3Kδ catalytic activity	87:110	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	1	15	theme	inflammatory	179:190	arg1	diseases					192:199	inflammatory diseases	179:199	inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive	179:276	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	4	16	theme	Structure-based	577:591	arg1	design					593:598	Structure-based design	577:598	Structure-based design	577:598	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
30986068	2	17	theme	diffuse	412:418	arg1	injury					429:434	diffuse vascular injury	412:434	diffuse vascular injury	412:434	A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury.
30986068	2	18	theme	vascular	420:427	arg1	injury					429:434	diffuse vascular injury	412:434	diffuse vascular injury	412:434	A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury.
30986068	2	19	theme	PI3Kδ	288:292	arg1	inhibitor					294:302	A purine PI3Kδ inhibitor	279:302	A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif	279:345	A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury.
30986068	0	20	theme	Purine	36:41	arg1	Inhibitor					49:57	a Potent Purine PI3Kδ Inhibitor	27:57	a Potent Purine PI3Kδ Inhibitor with Improved Tolerability	27:84	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability.
30986068	0	21	theme	Potent	29:34	arg1	Inhibitor					49:57	a Potent Purine PI3Kδ Inhibitor	27:57	a Potent Purine PI3Kδ Inhibitor with Improved Tolerability	27:84	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability.
30986068	5	22	theme	tolerability	833:844	arg1	study					846:850	a dog tolerability study	827:850	a dog tolerability study where it was found to be well tolerated	827:890	A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathological evidence of vascular injury.
30986068	4	23	link	N-linked	636:643	arg1	heterocycloalkyls					645:661	N-linked heterocycloalkyls	636:661	N-linked heterocycloalkyls	636:661	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
30986068	4	24	theme	improved	754:761	arg1	profile					783:789	an improved safety pharmacology profile	751:789	an improved safety pharmacology profile	751:789	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
30986068	0	25	theme	PI3Kδ	43:47	arg1	Inhibitor					49:57	a Potent Purine PI3Kδ Inhibitor	27:57	a Potent Purine PI3Kδ Inhibitor with Improved Tolerability	27:84	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability.
30986068	1	26	theme	immune	128:133	arg1	activation					140:149	immune cell activation	128:149	immune cell activation	128:149	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	1	27	theme	hematological	212:224	arg1	malignancies					226:237	hematological malignancies	212:237	inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive	179:276	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	1	28	from	malignancies	226:237	arg1	overactive					267:276	overactive	267:276	overactive	267:276	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	1	28	from	malignancies	226:237	arg1	pathway					256:262	the AKT pathway	248:262	the AKT pathway	248:262	PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematological malignancies in which the AKT pathway is overactive.
30986068	3	29	theme	motif	570:574	arg1	reconstruction					509:522	reconstruction	509:522	reconstruction of the benzimidazolone-piperidine selectivity motif	509:574	Several strategies were implemented to mitigate this finding, including reconstruction of the benzimidazolone-piperidine selectivity motif.
30986068	0	30	with	Inhibitor	49:57	arg1	Tolerability					73:84	Improved Tolerability	64:84	Improved Tolerability	64:84	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability.
30986068	2	31	theme	benzimidazolone-piperidine	314:339	arg1	motif					341:345	a benzimidazolone-piperidine motif	312:345	a benzimidazolone-piperidine motif	312:345	A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury.
30986068	4	32	theme	pharmacology	770:781	arg1	profile					783:789	an improved safety pharmacology profile	751:789	an improved safety pharmacology profile	751:789	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
30986068	0	33	theme	Improved	64:71	arg1	Tolerability					73:84	Improved Tolerability	64:84	Improved Tolerability	64:84	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability.
30986068	5	34	theme	vascular	931:938	arg1	injury					940:945	vascular injury	931:945	vascular injury	931:945	A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathological evidence of vascular injury.
30986068	5	35	with	advanced	813:820	arg1	evidence					919:926	no histopathological evidence	898:926	no histopathological evidence of vascular injury	898:945	A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathological evidence of vascular injury.
30986068	4	36	theme	N-linked	636:643	arg1	heterocycloalkyls					645:661	N-linked heterocycloalkyls	636:661	N-linked heterocycloalkyls	636:661	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
30986068	4	37	theme	heterocycloalkyls	645:661	arg1	identification					611:624	the identification	607:624	the identification of O- and N-linked heterocycloalkyls	607:661	Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacology profile.
29886537	0	0	theme	Prion	100:104	arg1	Protein					106:112	Prion Protein	100:112	Prion Protein	100:112	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	5	1	theme	outcomes	864:871	arg1	fate					830:833	the fate	826:833	the fate of prions in an organism and outcomes of prion infection	826:890	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	7	2	dep	Misfolding	1265:1274	arg1	Amplification					1283:1295	Cyclic Amplification	1276:1295	Protein Misfolding Cyclic Amplification	1257:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	3	theme	various	1143:1149	arg1	sources					1151:1157	various sources	1143:1157	various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1143:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	3	theme	various	1143:1149	arg1	organs					1212:1217	secondary lymphoid organs	1193:1217	secondary lymphoid organs	1193:1217	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	3	theme	various	1143:1149	arg1	PrPSc					1239:1243	PrPSc	1239:1243	PrPSc	1239:1243	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	3	theme	various	1143:1149	arg1	system					1185:1190	central nervous system	1169:1190	central nervous system	1169:1190	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	3	theme	various	1143:1149	arg1	cells					1229:1233	cultured cells	1220:1233	cultured cells	1220:1233	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	5	4	theme	prion	876:880	arg1	infection					882:890	prion infection	876:890	prion infection	876:890	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	5	5	theme	disease-associated	763:780	arg1	form					782:785	the disease-associated form	759:785	the disease-associated form of the prion protein or PrPSc	759:815	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	7	6	from	sources	1151:1157	arg1	status					1122:1127	sialylation status	1110:1127	sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1110:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	6	from	sources	1151:1157	arg1	PrPSc					1132:1136	PrPSc	1132:1136	PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1132:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	1	7	theme	neurodegenerative	172:188	arg1	disease					190:196	neurodegenerative disease	172:196	neurodegenerative disease	172:196	A number of proteins associated with neurodegenerative disease undergo several types of posttranslational modifications.
29886537	5	8	from	fate	830:833	arg1	organism					851:858	an organism	848:858	an organism	848:858	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	3	9	theme	physical	422:429	arg1	properties					431:440	physical properties	422:440	physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states	422:594	Posttranslational modifications alter physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states.
29886537	3	10	theme	proteins	445:452	arg1	properties					431:440	physical properties	422:440	physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states	422:594	Posttranslational modifications alter physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states.
29886537	5	11	theme	form	782:785	arg1	sialylation					744:754	sialylation	744:754	sialylation of the disease-associated form of the prion protein or PrPSc	744:815	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	6	12	theme	sialylation	907:917	arg1	status					919:924	sialylation status	907:924	sialylation status of PrPSc	907:933	For assessing sialylation status of PrPSc, we developed a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D).
29886537	2	13	theme	protein	335:341	arg1	phosphorylation					344:358	phosphorylation	344:358	phosphorylation of tau	344:365	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	13	theme	protein	335:341	arg1	glycosylation					278:290	N-linked glycosylation	269:290	N-linked glycosylation of the prion protein and amyloid precursor protein	269:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	13	theme	protein	335:341	arg1	α-synuclein					371:381	α-synuclein	371:381	α-synuclein	371:381	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	5	14	theme	prions	838:843	arg1	fate					830:833	the fate	826:833	the fate of prions in an organism and outcomes of prion infection	826:890	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	5	15	theme	Recent	713:718	arg1	studies					720:726	Recent studies	713:726	Recent studies	713:726	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	2	16	theme	precursor	325:333	arg1	protein					335:341	amyloid precursor protein	317:341	amyloid precursor protein	317:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	7	17	from	status	1122:1127	arg1	sources					1151:1157	various sources	1143:1157	various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1143:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	17	from	status	1122:1127	arg1	organs					1212:1217	secondary lymphoid organs	1193:1217	secondary lymphoid organs	1193:1217	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	17	from	status	1122:1127	arg1	PrPSc					1239:1243	PrPSc	1239:1243	PrPSc	1239:1243	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	17	from	status	1122:1127	arg1	system					1185:1190	central nervous system	1169:1190	central nervous system	1169:1190	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	17	from	status	1122:1127	arg1	cells					1229:1233	cultured cells	1220:1233	cultured cells	1220:1233	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	2	18	theme	amyloid	317:323	arg1	protein					335:341	amyloid precursor protein	317:341	amyloid precursor protein	317:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	3	19	theme	surface	478:484	arg1	charges					486:492	their net and surface charges	464:492	charges	486:492	Posttranslational modifications alter physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states.
29886537	6	20	theme	a reliable	949:958	arg1	protocol					960:967	a reliable protocol	949:967	a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D)	949:1043	For assessing sialylation status of PrPSc, we developed a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D).
29886537	6	21	theme	two-dimensional	983:997	arg1	electrophoresis					999:1013	two-dimensional electrophoresis	983:1013	two-dimensional electrophoresis followed by Western blot (2D)	983:1043	For assessing sialylation status of PrPSc, we developed a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D).
29886537	7	22	theme	secondary	1193:1201	arg1	organs					1212:1217	secondary lymphoid organs	1193:1217	secondary lymphoid organs	1193:1217	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	23	theme	current	1050:1056	arg1	chapter					1058:1064	The current chapter	1046:1064	The current chapter	1046:1064	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	2	24	theme	tau	363:365	arg1	phosphorylation					344:358	phosphorylation	344:358	phosphorylation of tau	344:365	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	24	theme	tau	363:365	arg1	glycosylation					278:290	N-linked glycosylation	269:290	N-linked glycosylation of the prion protein and amyloid precursor protein	269:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	24	theme	tau	363:365	arg1	α-synuclein					371:381	α-synuclein	371:381	α-synuclein	371:381	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	1	25	theme	several	206:212	arg1	types					214:218	several types	206:218	several types of posttranslational modifications	206:253	A number of proteins associated with neurodegenerative disease undergo several types of posttranslational modifications.
29886537	4	26	theme	modifications	636:648	arg1	analysis					606:613	analysis	606:613	analysis of posttranslational modifications	606:648	As such, analysis of posttranslational modifications is important for understanding the mechanisms of pathogenesis.
29886537	7	27	theme	lymphoid	1203:1210	arg1	organs					1212:1217	secondary lymphoid organs	1193:1217	secondary lymphoid organs	1193:1217	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	28	theme	nervous	1177:1183	arg1	system					1185:1190	central nervous system	1169:1190	central nervous system	1169:1190	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	0	29	theme	Modifications	21:33	arg1	Analysis					0:7	Analysis	0:7	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.	0:133	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	4	30	theme	posttranslational	618:634	arg1	modifications					636:648	posttranslational modifications	618:648	posttranslational modifications	618:648	As such, analysis of posttranslational modifications is important for understanding the mechanisms of pathogenesis.
29886537	5	31	theme	PrPSc	811:815	arg1	form					782:785	the disease-associated form	759:785	the disease-associated form of the prion protein or PrPSc	759:815	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	0	32	theme	Covalent	12:19	arg1	Modifications					21:33	Covalent Modifications	12:33	Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis	12:97	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	3	33	dep	misfolded	559:567	arg1	disease-associated					570:587	disease-associated	570:587	disease-associated	570:587	Posttranslational modifications alter physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states.
29886537	5	34	from	prions	838:843	arg1	organism					851:858	an organism	848:858	an organism	848:858	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	7	35	theme	Protein	1257:1263	arg1	Misfolding					1265:1274	Protein Misfolding Cyclic Amplification	1257:1295	Protein Misfolding Cyclic Amplification	1257:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	1	36	theme	posttranslational	223:239	arg1	modifications					241:253	posttranslational modifications	223:253	posttranslational modifications	223:253	A number of proteins associated with neurodegenerative disease undergo several types of posttranslational modifications.
29886537	0	37	theme	Amyloidogenic	38:50	arg1	Proteins					52:59	Amyloidogenic Proteins	38:59	Amyloidogenic Proteins Using Two-Dimensional Electrophoresis	38:97	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	7	38	theme	central	1169:1175	arg1	system					1185:1190	central nervous system	1169:1190	central nervous system	1169:1190	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	1	39	theme	modifications	241:253	arg1	types					214:218	several types	206:218	several types of posttranslational modifications	206:253	A number of proteins associated with neurodegenerative disease undergo several types of posttranslational modifications.
29886537	2	40	gly	glycosylation	278:290	arg1	protein					335:341	amyloid precursor protein	317:341	amyloid precursor protein	317:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	40	gly	glycosylation	278:290	arg1	protein					305:311	the prion protein	295:311	the prion protein	295:311	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	40	gly	glycosylation	278:290	arg1	tau					363:365	tau	363:365	tau	363:365	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	5	41	theme	infection	882:890	arg1	outcomes					864:871	outcomes	864:871	outcomes of prion infection	864:890	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	5	41	theme	infection	882:890	arg1	prions					838:843	prions	838:843	prions in an organism	838:858	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	2	42	theme	N-linked	269:276	arg1	glycosylation					278:290	N-linked glycosylation	269:290	N-linked glycosylation of the prion protein and amyloid precursor protein	269:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	5	43	gly	sialylation	744:754	arg1	form					782:785	the disease-associated form	759:785	the disease-associated form of the prion protein or PrPSc	759:815	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	3	44	theme	Posttranslational	384:400	arg1	modifications					402:414	Posttranslational modifications	384:414	Posttranslational modifications	384:414	Posttranslational modifications alter physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states.
29886537	7	45	theme	PrPSc	1132:1136	arg1	status					1122:1127	sialylation status	1110:1127	sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1110:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	3	46	theme	misfolded	559:567	arg1	states					589:594	misfolded, disease-associated states	559:594	misfolded, disease-associated states	559:594	Posttranslational modifications alter physical properties of proteins including their net and surface charges, affecting their processing, life-time and propensity to acquire misfolded, disease-associated states.
29886537	0	47	theme	Proteins	52:59	arg1	Modifications					21:33	Covalent Modifications	12:33	Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis	12:97	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	5	48	theme	prion	794:798	arg1	protein					800:806	the prion protein	790:806	the prion protein	790:806	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	5	49	from	outcomes	864:871	arg1	organism					851:858	an organism	848:858	an organism	848:858	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	7	50	theme	sialylation	1110:1120	arg1	status					1122:1127	sialylation status	1110:1127	sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1110:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	51	theme	cultured	1220:1227	arg1	cells					1229:1233	cultured cells	1220:1233	cultured cells	1220:1233	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	6	52	gly	sialylation	907:917	arg1	PrPSc					929:933	PrPSc	929:933	PrPSc	929:933	For assessing sialylation status of PrPSc, we developed a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D).
29886537	5	53	theme	protein	800:806	arg1	form					782:785	the disease-associated form	759:785	the disease-associated form of the prion protein or PrPSc	759:815	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	2	54	theme	protein	305:311	arg1	phosphorylation					344:358	phosphorylation	344:358	phosphorylation of tau	344:365	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	54	theme	protein	305:311	arg1	glycosylation					278:290	N-linked glycosylation	269:290	N-linked glycosylation of the prion protein and amyloid precursor protein	269:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	2	54	theme	protein	305:311	arg1	α-synuclein					371:381	α-synuclein	371:381	α-synuclein	371:381	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	7	55	gly	sialylation	1110:1120	arg1	PrPSc					1132:1136	PrPSc	1132:1136	PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1132:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	7	56	theme	status	1122:1127	arg1	analysis					1098:1105	the analysis	1094:1105	the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification	1094:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	5	57	from	organism	851:858	arg1	fate					830:833	the fate	826:833	the fate of prions in an organism and outcomes of prion infection	826:890	Recent studies documented that sialylation of the disease-associated form of the prion protein or PrPSc controls the fate of prions in an organism and outcomes of prion infection.
29886537	2	58	theme	prion	299:303	arg1	protein					305:311	the prion protein	295:311	the prion protein	295:311	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
29886537	4	59	theme	pathogenesis	699:710	arg1	the mechanisms					681:694	the mechanisms	681:694	the mechanisms of pathogenesis	681:710	As such, analysis of posttranslational modifications is important for understanding the mechanisms of pathogenesis.
29886537	6	60	theme	PrPSc	929:933	arg1	status					919:924	sialylation status	907:924	sialylation status of PrPSc	907:933	For assessing sialylation status of PrPSc, we developed a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D).
29886537	1	61	theme	proteins	147:154	arg1	number					137:142	A number	135:142	A number of proteins associated with neurodegenerative disease	135:196	A number of proteins associated with neurodegenerative disease undergo several types of posttranslational modifications.
29886537	6	62	theme	Western	1027:1033	arg1	blot					1035:1038	Western blot	1027:1038	Western blot (2D)	1027:1043	For assessing sialylation status of PrPSc, we developed a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D).
29886537	6	62	theme	Western	1027:1033	arg1	2D					1041:1042	2D	1041:1042	2D	1041:1042	For assessing sialylation status of PrPSc, we developed a reliable protocol that involves two-dimensional electrophoresis followed by Western blot (2D).
29886537	0	63	theme	Two-Dimensional	67:81	arg1	Electrophoresis					83:97	Two-Dimensional Electrophoresis	67:97	Two-Dimensional Electrophoresis	67:97	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	0	64	dep	Analysis	0:7	arg1	Protein					106:112	Prion Protein	100:112	Prion Protein	100:112	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	0	64	dep	Analysis	0:7	arg1	Sialylation					122:132	Its Sialylation	118:132	Its Sialylation	118:132	Analysis of Covalent Modifications of Amyloidogenic Proteins Using Two-Dimensional Electrophoresis: Prion Protein and Its Sialylation.
29886537	7	65	theme	Cyclic	1276:1281	arg1	Amplification					1283:1295	Cyclic Amplification	1276:1295	Protein Misfolding Cyclic Amplification	1257:1295	The current chapter describes the procedure for the analysis of sialylation status of PrPSc from various sources including central nervous system, secondary lymphoid organs, cultured cells, or PrPSc produced in Protein Misfolding Cyclic Amplification.
29886537	2	66	link	N-linked	269:276	arg1	glycosylation					278:290	N-linked glycosylation	269:290	N-linked glycosylation of the prion protein and amyloid precursor protein	269:341	They include N-linked glycosylation of the prion protein and amyloid precursor protein, phosphorylation of tau and α-synuclein.
31196789	0	0	theme	laccase	74:80	arg1	Lcc9					82:85	a Coprinopsis cinerea laccase Lcc9	52:85	a Coprinopsis cinerea laccase Lcc9	52:85	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	1	1	theme	specific	248:255	arg1	activity					257:264	specific activity	248:264	specific activity	248:264	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	0	2	theme	cinerea	66:72	arg1	Lcc9					82:85	a Coprinopsis cinerea laccase Lcc9	52:85	a Coprinopsis cinerea laccase Lcc9	52:85	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	1	3	from	cinerea	147:153	arg1	Lcc9					125:128	Laccase Lcc9	117:128	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9)	117:205	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	3	4	gly	deglycosylated	504:517	arg1	them					519:522	them	519:522	them	519:522	To elucidate this hypothesis, in this study, firstly we demonstrated that rLcc9 and nLcc9 were glycoproteins, and then enzymatically deglycosylated them.
31196789	9	5	theme	biochemical	1364:1374	arg1	characteristics					1376:1390	biochemical characteristics	1364:1390	biochemical characteristics of fungal laccases	1364:1409	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	4	6	from	decrease	575:582	arg1	activities					602:611	their specific activities	587:611	their specific activities	587:611	The obtained drLcc9 and dnLcc9 showed an apparent decrease in their specific activities.
31196789	0	7	from	Role	0:3	arg1	activity					40:47	the specific activity	27:47	the specific activity of a Coprinopsis cinerea laccase Lcc9	27:85	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	6	8	theme	weight	778:783	arg1	analysis					785:792	Molecular weight analysis	768:792	Molecular weight analysis on those mutants	768:809	Molecular weight analysis on those mutants suggested that glycosylation should have occurred on N313 and N454 whereas not on N293 in rLcc9.
31196789	9	9	theme	N-linked	1491:1498	arg1	modification					1514:1525	N-linked glycosylation modification	1491:1525	N-linked glycosylation modification	1491:1525	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	0	10	theme	Lcc9	82:85	arg1	activity					40:47	the specific activity	27:47	the specific activity of a Coprinopsis cinerea laccase Lcc9	27:85	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	9	11	theme	fungal	1458:1463	arg1	activity					1473:1480	fungal laccase activity	1458:1480	fungal laccase activity	1458:1480	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	7	12	theme	catalytic	1070:1078	arg1	rate					1080:1083	the catalytic rate	1066:1083	the catalytic rate	1066:1083	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	6	13	theme	Molecular	768:776	arg1	analysis					785:792	Molecular weight analysis	768:792	Molecular weight analysis on those mutants	768:809	Molecular weight analysis on those mutants suggested that glycosylation should have occurred on N313 and N454 whereas not on N293 in rLcc9.
31196789	9	14	theme	glycosylation	1500:1512	arg1	modification					1514:1525	N-linked glycosylation modification	1491:1525	N-linked glycosylation modification	1491:1525	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	4	15	theme	apparent	566:573	arg1	decrease					575:582	an apparent decrease	563:582	an apparent decrease in their specific activities	563:611	The obtained drLcc9 and dnLcc9 showed an apparent decrease in their specific activities.
31196789	0	16	theme	Pichia	100:105	arg1	pastoris					107:114	Pichia pastoris	100:114	Pichia pastoris	100:114	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	8	17	from	decreases	1239:1247	arg1	stability					1266:1274	their thermal stability	1252:1274	their thermal stability to some extent	1252:1289	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	6	18	from	analysis	785:792	arg1	mutants					803:809	those mutants	797:809	those mutants	797:809	Molecular weight analysis on those mutants suggested that glycosylation should have occurred on N313 and N454 whereas not on N293 in rLcc9.
31196789	9	19	theme	fungal	1395:1400	arg1	laccases					1402:1409	fungal laccases	1395:1409	fungal laccases	1395:1409	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	6	20	dep	not	886:888	arg1	whereas					878:884	whereas	878:884	whereas	878:884	Molecular weight analysis on those mutants suggested that glycosylation should have occurred on N313 and N454 whereas not on N293 in rLcc9.
31196789	7	21	from	N454	1000:1003	arg1	glycosylation					974:986	glycosylation	974:986	glycosylation at N313 and N454 in rLcc9	974:1012	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	8	22	theme	nLcc9	1184:1188	arg1	stability					1161:1169	the thermal stability	1149:1169	the thermal stability of rLcc9 and nLcc9	1149:1188	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	8	23	theme	thermal	1258:1264	arg1	stability					1266:1274	their thermal stability	1252:1274	their thermal stability to some extent	1252:1289	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	5	24	theme	putative	620:627	arg1	N313					658:661	N313	658:661	N313	658:661	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	24	theme	putative	620:627	arg1	N454					668:671	N454	668:671	N454	668:671	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	24	theme	putative	620:627	arg1	N293					652:655	N293	652:655	N293	652:655	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	24	theme	putative	620:627	arg1	sites					645:649	Three putative N-glycosylation sites	614:649	Three putative N-glycosylation sites (N293, N313, and N454)	614:672	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	3	25	gly	glycoproteins	466:478	arg1	glycoproteins					466:478	glycoproteins	466:478	glycoproteins	466:478	To elucidate this hypothesis, in this study, firstly we demonstrated that rLcc9 and nLcc9 were glycoproteins, and then enzymatically deglycosylated them.
31196789	1	26	theme	Pichia	183:188	arg1	rLcc9					200:204	rLcc9	200:204	rLcc9	200:204	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	1	26	theme	Pichia	183:188	arg1	pastoris					190:197	Pichia pastoris	183:197	Pichia pastoris (rLcc9)	183:205	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	1	27	theme	native	275:280	arg1	nLcc9					291:295	nLcc9	291:295	nLcc9	291:295	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	1	27	theme	native	275:280	arg1	laccase					282:288	the native laccase	271:288	the native laccase (nLcc9)	271:296	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	1	28	from	laccase	282:288	arg1	weight					237:242	different molecular weight	217:242	different molecular weight	217:242	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	1	28	from	laccase	282:288	arg1	activity					257:264	specific activity	248:264	specific activity	248:264	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	9	29	theme	activity	1473:1480	arg1	improvement					1443:1453	the improvement	1439:1453	the improvement of fungal laccase activity based on N-linked glycosylation modification	1439:1525	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	5	30	dep	sites	645:649	arg1	N313					658:661	N313	658:661	N313	658:661	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	30	dep	sites	645:649	arg1	N454					668:671	N454	668:671	N454	668:671	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	30	dep	sites	645:649	arg1	N293					652:655	N293	652:655	N293	652:655	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	30	dep	sites	645:649	arg1	sites					645:649	Three putative N-glycosylation sites	614:649	Three putative N-glycosylation sites (N293, N313, and N454)	614:672	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	4	31	theme	obtained	529:536	arg1	drLcc9					538:543	drLcc9	538:543	drLcc9	538:543	The obtained drLcc9 and dnLcc9 showed an apparent decrease in their specific activities.
31196789	7	32	theme	catalytic	922:930	arg1	properties					932:941	catalytic properties	922:941	catalytic properties of those mutants	922:958	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	8	33	theme	Lcc9s	1221:1225	arg1	deglycosylation					1196:1210	deglycosylation	1196:1210	deglycosylation of those Lcc9s	1196:1225	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	0	34	theme	N-glycosylation	8:22	arg1	Role					0:3	Role	0:3	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9	0:85	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	7	35	theme	binding	1031:1037	arg1	affinity					1039:1046	the binding affinity	1027:1046	the binding affinity to substrates	1027:1060	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	7	36	from	glycosylation	974:986	arg1	rLcc9					1008:1012	rLcc9	1008:1012	rLcc9	1008:1012	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	0	37	theme	specific	31:38	arg1	activity					40:47	the specific activity	27:47	the specific activity of a Coprinopsis cinerea laccase Lcc9	27:85	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	6	38	gly	glycosylation	826:838	arg2	N293					893:896	N293	893:896	N293 in rLcc9	893:905	Molecular weight analysis on those mutants suggested that glycosylation should have occurred on N313 and N454 whereas not on N293 in rLcc9.
31196789	6	38	gly	glycosylation	826:838	arg2	N313					864:867	N313	864:867	N313	864:867	Molecular weight analysis on those mutants suggested that glycosylation should have occurred on N313 and N454 whereas not on N293 in rLcc9.
31196789	5	39	gly	N-glycosylation	629:643	arg2	N313					658:661	N313	658:661	N313	658:661	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	39	gly	N-glycosylation	629:643	arg2	N293					652:655	N293	652:655	N293	652:655	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	39	gly	N-glycosylation	629:643	arg2	N454					668:671	N454	668:671	N454	668:671	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	39	gly	N-glycosylation	629:643	arg2	sites					645:649	Three putative N-glycosylation sites	614:649	Three putative N-glycosylation sites (N293, N313, and N454)	614:672	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	39	gly	N-glycosylation	629:643	arg2	Three					614:618	Three	614:618	Three	614:618	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	8	40	gly	deglycosylation	1196:1210	arg1	Lcc9s					1221:1225	those Lcc9s	1215:1225	those Lcc9s	1215:1225	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	8	41	theme	thermal	1153:1159	arg1	stability					1161:1169	the thermal stability	1149:1169	the thermal stability of rLcc9 and nLcc9	1149:1188	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	7	42	from	N313	991:994	arg1	glycosylation					974:986	glycosylation	974:986	glycosylation at N313 and N454 in rLcc9	974:1012	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	5	43	theme	specific	749:756	arg1	activity					758:765	its specific activity	745:765	its specific activity	745:765	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	9	44	gly	glycosylation	1347:1359	arg1	laccases					1402:1409	fungal laccases	1395:1409	fungal laccases	1395:1409	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	8	45	theme	rLcc9	1174:1178	arg1	stability					1161:1169	the thermal stability	1149:1169	the thermal stability of rLcc9 and nLcc9	1149:1188	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	7	46	gly	glycosylation	974:986	arg2	N313					991:994	N313	991:994	N313	991:994	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	7	46	gly	glycosylation	974:986	arg1	N454					1000:1003	N454	1000:1003	N454	1000:1003	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	7	46	gly	glycosylation	974:986	arg1	rLcc9					1008:1012	rLcc9	1008:1012	rLcc9	1008:1012	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	7	46	gly	glycosylation	974:986	arg2	N454					1000:1003	N454	1000:1003	N454	1000:1003	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	7	46	gly	glycosylation	974:986	arg1	N313					991:994	N313	991:994	N313	991:994	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	7	46	gly	glycosylation	974:986	arg1	binding					1031:1037	the binding affinity	1027:1046	the binding affinity to substrates	1027:1060	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	6	47	from	N293	893:896	arg1	rLcc9					901:905	rLcc9	901:905	rLcc9	901:905	Molecular weight analysis on those mutants suggested that glycosylation should have occurred on N313 and N454 whereas not on N293 in rLcc9.
31196789	9	48	link	N-linked	1491:1498	arg1	modification					1514:1525	N-linked glycosylation modification	1491:1525	N-linked glycosylation modification	1491:1525	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	9	49	theme	us	1424:1425	arg1	support					1427:1433	us support	1424:1433	us support for the improvement of fungal laccase activity based on N-linked glycosylation modification	1424:1525	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	5	50	theme	N-glycosylation	629:643	arg1	N313					658:661	N313	658:661	N313	658:661	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	50	theme	N-glycosylation	629:643	arg1	N454					668:671	N454	668:671	N454	668:671	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	50	theme	N-glycosylation	629:643	arg1	N293					652:655	N293	652:655	N293	652:655	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	50	theme	N-glycosylation	629:643	arg1	sites					645:649	Three putative N-glycosylation sites	614:649	Three putative N-glycosylation sites (N293, N313, and N454)	614:672	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	5	51	from	roles	736:740	arg1	activity					758:765	its specific activity	745:765	its specific activity	745:765	Three putative N-glycosylation sites (N293, N313, and N454) were then predicted in Lcc9 and substituted to evaluate their roles in its specific activity.
31196789	7	52	theme	properties	932:941	arg1	Comparison					908:917	Comparison	908:917	Comparison of catalytic properties of those mutants	908:958	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	1	53	theme	Laccase	117:123	arg1	Lcc9					125:128	Laccase Lcc9	117:128	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9)	117:205	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	1	54	theme	different	217:225	arg1	weight					237:242	different molecular weight	217:242	different molecular weight	217:242	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	9	55	from	effect	1337:1342	arg1	characteristics					1376:1390	biochemical characteristics	1364:1390	biochemical characteristics of fungal laccases	1364:1409	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	3	56	dep	demonstrated	427:438	arg1	elucidate					374:382	elucidate	374:382	elucidate	374:382	To elucidate this hypothesis, in this study, firstly we demonstrated that rLcc9 and nLcc9 were glycoproteins, and then enzymatically deglycosylated them.
31196789	7	57	theme	mutants	952:958	arg1	properties					932:941	catalytic properties	922:941	catalytic properties of those mutants	922:958	Comparison of catalytic properties of those mutants revealed that glycosylation at N313 and N454 in rLcc9 could affect the binding affinity to substrates and the catalytic rate, respectively.
31196789	1	58	theme	Coprinopsis	135:145	arg1	cinerea					147:153	Coprinopsis cinerea	135:153	Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9)	135:205	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	1	59	theme	molecular	227:235	arg1	weight					237:242	different molecular weight	217:242	different molecular weight	217:242	Laccase Lcc9 from Coprinopsis cinerea heterologously expressed in Pichia pastoris (rLcc9) displayed different molecular weight and specific activity from the native laccase (nLcc9).
31196789	0	60	theme	Coprinopsis	54:64	arg1	Lcc9					82:85	a Coprinopsis cinerea laccase Lcc9	52:85	a Coprinopsis cinerea laccase Lcc9	52:85	Role of N-glycosylation on the specific activity of a Coprinopsis cinerea laccase Lcc9 expressed in Pichia pastoris.
31196789	9	61	theme	laccase	1465:1471	arg1	activity					1473:1480	fungal laccase activity	1458:1480	fungal laccase activity	1458:1480	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	2	62	theme	specific	352:359	arg1	activity					361:368	the Lcc9 specific activity	343:368	the Lcc9 specific activity	343:368	Glycosylation may play a role in regulating the Lcc9 specific activity.
31196789	9	63	theme	laccases	1402:1409	arg1	characteristics					1376:1390	biochemical characteristics	1364:1390	biochemical characteristics of fungal laccases	1364:1409	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	9	64	theme	glycosylation	1347:1359	arg1	effect					1337:1342	the effect	1333:1342	the effect of glycosylation on biochemical characteristics of fungal laccases	1333:1409	These results will help us to understand the effect of glycosylation on biochemical characteristics of fungal laccases, and provide us support for the improvement of fungal laccase activity based on N-linked glycosylation modification.
31196789	8	65	gly	glycosylation	1117:1129	arg1	nLcc9					1184:1188	nLcc9	1184:1188	nLcc9	1184:1188	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	8	65	gly	glycosylation	1117:1129	arg1	rLcc9					1174:1178	rLcc9	1174:1178	rLcc9	1174:1178	In addition, the glycosylation could also affect the thermal stability of rLcc9 and nLcc9 since deglycosylation of those Lcc9s resulted in decreases in their thermal stability to some extent.
31196789	2	66	theme	Lcc9	347:350	arg1	activity					361:368	the Lcc9 specific activity	343:368	the Lcc9 specific activity	343:368	Glycosylation may play a role in regulating the Lcc9 specific activity.
31196789	4	67	theme	specific	593:600	arg1	activities					602:611	their specific activities	587:611	their specific activities	587:611	The obtained drLcc9 and dnLcc9 showed an apparent decrease in their specific activities.
30523150	7	0	theme	differentiation	1467:1481	arg1	regulation					1439:1448	the regulation	1435:1448	the regulation of hematopoietic differentiation	1435:1481	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	4	1	theme	GATA-1	869:874	arg1	interactions					853:864	physical interactions	844:864	physical interactions of GATA-1 with both OGT and OGA	844:896	We observed that during G1E-ER4 differentiation, overall O-GlcNAc levels decrease, and physical interactions of GATA-1 with both OGT and OGA increase.
30523150	2	2	from	process	414:420	arg1	formation					436:444	blood cell formation	425:444	blood cell formation	425:444	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	6	3	theme	ChIP	1089:1092	arg1	results					1094:1100	ChIP results	1089:1100	ChIP results	1089:1100	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	3	4	from	role	490:493	arg1	erythropoiesis					517:530	erythropoiesis	517:530	erythropoiesis	517:530	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	7	5	gly	O-GlcNAcylation	1404:1418	arg1	regulation					1439:1448	the regulation	1435:1448	the regulation of hematopoietic differentiation	1435:1481	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	3	6	theme	G1E-ER4	541:547	arg1	cells					549:553	G1E-ER4 cells	541:553	G1E-ER4 cells	541:553	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	9	7	theme	transcriptional	1700:1714	arg1	programs					1716:1723	transcriptional programs	1700:1723	transcriptional programs controlling erythropoietic lineage commitment	1700:1769	Our results show that alterations in O-GlcNAcylation disrupt transcriptional programs controlling erythropoietic lineage commitment, suggesting a role for O-GlcNAcylation in regulating hematopoietic cell fate.
30523150	6	8	theme	transmembrane	1233:1245	arg1	promoter					1263:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	7	9	theme	leukemia	1372:1379	arg1	cells					1381:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	6	10	theme	lysosomal	1215:1223	arg1	promoter					1263:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	2	11	theme	cellular	306:313	arg1	differentiation					315:329	cellular differentiation	306:329	cellular differentiation	306:329	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	9	12	theme	lineage	1752:1758	arg1	commitment					1760:1769	erythropoietic lineage commitment	1737:1769	erythropoietic lineage commitment	1737:1769	Our results show that alterations in O-GlcNAcylation disrupt transcriptional programs controlling erythropoietic lineage commitment, suggesting a role for O-GlcNAcylation in regulating hematopoietic cell fate.
30523150	7	13	theme	NB4	1345:1347	arg1	cells					1381:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	7	14	theme	human	1358:1362	arg1	cells					1381:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	5	15	theme	target	1075:1080	arg1	genes					1082:1086	433 GATA-1 target genes	1064:1086	433 GATA-1 target genes	1064:1086	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	3	16	theme	factor	605:610	arg1	GATA-1					636:641	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1)	568:642	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER)	568:685	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	3	17	theme	erythroid-specific	572:589	arg1	GATA-1					636:641	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1)	568:642	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER)	568:685	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	5	18	theme	RNA-Seq-based	908:920	arg1	analysis					936:943	RNA-Seq-based transcriptome analysis	908:943	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG)	908:1028	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	2	19	from	Changes	262:268	arg1	O-GlcNAcylation					281:295	protein O-GlcNAcylation	273:295	protein O-GlcNAcylation	273:295	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	5	20	theme	cells	956:960	arg1	analysis					936:943	RNA-Seq-based transcriptome analysis	908:943	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG)	908:1028	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	6	21	theme	promoter	1263:1270	arg1	site					1203:1206	the GATA-binding site	1186:1206	the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1186:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	6	21	theme	promoter	1263:1270	arg1	promoter					1263:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	7	22	theme	genes	1308:1312	arg1	expression					1294:1303	the expression	1290:1303	the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells	1290:1385	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	3	23	theme	protein	625:631	arg1	GATA-1					636:641	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1)	568:642	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER)	568:685	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	4	24	with	interactions	853:864	arg1	OGA					894:896	OGA	894:896	OGA	894:896	We observed that during G1E-ER4 differentiation, overall O-GlcNAc levels decrease, and physical interactions of GATA-1 with both OGT and OGA increase.
30523150	4	24	with	interactions	853:864	arg1	OGT					886:888	OGT	886:888	OGT	886:888	We observed that during G1E-ER4 differentiation, overall O-GlcNAc levels decrease, and physical interactions of GATA-1 with both OGT and OGA increase.
30523150	9	25	theme	hematopoietic	1824:1836	arg1	fate					1843:1846	hematopoietic cell fate	1824:1846	hematopoietic cell fate	1824:1846	Our results show that alterations in O-GlcNAcylation disrupt transcriptional programs controlling erythropoietic lineage commitment, suggesting a role for O-GlcNAcylation in regulating hematopoietic cell fate.
30523150	8	26	theme	hemoglobin-positive	1561:1579	arg1	cells					1581:1585	hemoglobin-positive cells	1561:1585	hemoglobin-positive cells	1561:1585	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	8	27	theme	G1E-ER4	1507:1513	arg1	cells					1515:1519	G1E-ER4 cells	1507:1519	G1E-ER4 cells	1507:1519	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	0	28	theme	O-GlcNAc	0:7	arg1	homeostasis					9:19	O-GlcNAc homeostasis	0:19	O-GlcNAc homeostasis	0:19	O-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis.
30523150	5	29	theme	G1E-ER4	948:954	arg1	cells					956:960	G1E-ER4 cells	948:960	G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG)	948:1028	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	2	30	theme	cell	431:434	arg1	formation					436:444	blood cell formation	425:444	blood cell formation	425:444	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	6	31	theme	OGA	1179:1181	arg1	occupancy					1149:1157	the occupancy	1145:1157	the occupancy of GATA-1, OGT, and OGA	1145:1181	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	1	32	theme	β-d-GlcNAc	103:112	arg1	O-GlcNAc					121:128	O-GlcNAc	121:128	O-GlcNAc	121:128	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	1	32	theme	β-d-GlcNAc	103:112	arg1	sugar					114:118	a single β-d-GlcNAc sugar	94:118	a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT)	94:159	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	9	33	theme	erythropoietic	1737:1750	arg1	commitment					1760:1769	erythropoietic lineage commitment	1737:1769	erythropoietic lineage commitment	1737:1769	Our results show that alterations in O-GlcNAcylation disrupt transcriptional programs controlling erythropoietic lineage commitment, suggesting a role for O-GlcNAcylation in regulating hematopoietic cell fate.
30523150	4	34	theme	O-GlcNAc	814:821	arg1	levels					823:828	overall O-GlcNAc levels	806:828	overall O-GlcNAc levels	806:828	We observed that during G1E-ER4 differentiation, overall O-GlcNAc levels decrease, and physical interactions of GATA-1 with both OGT and OGA increase.
30523150	2	35	theme	essential	404:412	arg1	process					414:420	an essential process	401:420	an essential process	401:420	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	0	36	theme	cell	36:39	arg1	decisions					46:54	cell fate decisions	36:54	cell fate decisions	36:54	O-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis.
30523150	6	37	theme	TMG	1121:1123	arg1	treatment					1125:1133	the TMG treatment	1117:1133	the TMG treatment	1117:1133	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	8	38	theme	increased	1591:1599	arg1	markers					1630:1636	increased stem/progenitor cell surface markers	1591:1636	increased stem/progenitor cell surface markers	1591:1636	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	4	39	theme	G1E-ER4	781:787	arg1	differentiation					789:803	G1E-ER4 differentiation	781:803	G1E-ER4 differentiation	781:803	We observed that during G1E-ER4 differentiation, overall O-GlcNAc levels decrease, and physical interactions of GATA-1 with both OGT and OGA increase.
30523150	2	40	theme	cell	335:338	arg1	decisions					345:353	cell fate decisions	335:353	cell fate decisions	335:353	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	5	41	theme	OGA	1000:1002	arg1	TMG					1025:1027	TMG	1025:1027	TMG	1025:1027	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	5	41	theme	OGA	1000:1002	arg1	Thiamet-G					1014:1022	the OGA inhibitor Thiamet-G	996:1022	the OGA inhibitor Thiamet-G (TMG)	996:1028	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	8	42	theme	cell	1617:1620	arg1	markers					1630:1636	increased stem/progenitor cell surface markers	1591:1636	increased stem/progenitor cell surface markers	1591:1636	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	3	43	theme	estrogen	657:664	arg1	GATA-1-ER					676:684	GATA-1-ER	676:684	GATA-1-ER	676:684	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	3	43	theme	estrogen	657:664	arg1	receptor					666:673	estrogen receptor	657:673	the estrogen receptor (GATA-1-ER)	653:685	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	3	44	theme	O-GlcNAcylation	498:512	arg1	role					490:493	the role	486:493	the role of O-GlcNAcylation in erythropoiesis	486:530	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	1	45	theme	homeostatic	212:222	arg1	levels					233:238	homeostatic O-GlcNAc levels	212:238	homeostatic O-GlcNAc levels on cellular proteins	212:259	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	7	46	theme	hematopoietic	1453:1465	arg1	differentiation					1467:1481	hematopoietic differentiation	1453:1481	hematopoietic differentiation	1453:1481	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	5	47	theme	Thiamet-G	1014:1022	arg1	presence					984:991	the presence	980:991	the presence of the OGA inhibitor Thiamet-G (TMG)	980:1028	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	6	48	theme	gene	1258:1261	arg1	promoter					1263:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	6	49	theme	Laptm5	1250:1255	arg1	promoter					1263:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	2	50	theme	protein	273:279	arg1	O-GlcNAcylation					281:295	protein O-GlcNAcylation	273:295	protein O-GlcNAcylation	273:295	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	1	51	theme	cellular	243:250	arg1	proteins					252:259	cellular proteins	243:259	cellular proteins	243:259	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	6	52	theme	OGT	1170:1172	arg1	occupancy					1149:1157	the occupancy	1145:1157	the occupancy of GATA-1, OGT, and OGA	1145:1181	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	3	53	theme	β-estradiol	730:740	arg1	addition					747:754	β-estradiol (E2) addition	730:754	β-estradiol (E2) addition	730:754	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	6	54	theme	GATA-1	1162:1167	arg1	occupancy					1149:1157	the occupancy	1145:1157	the occupancy of GATA-1, OGT, and OGA	1145:1181	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	6	55	gly	occupancy	1149:1157	arg2	OGT					1170:1172	OGT	1170:1172	OGT	1170:1172	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	6	55	gly	occupancy	1149:1157	arg2	GATA-1					1162:1167	GATA-1	1162:1167	GATA-1	1162:1167	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	6	55	gly	occupancy	1149:1157	arg2	OGA					1179:1181	OGA	1179:1181	OGA	1179:1181	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	6	56	theme	protein	1225:1231	arg1	promoter					1263:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	1	57	theme	O-GlcNAc	165:172	arg1	removal					174:180	O-GlcNAc removal	165:180	O-GlcNAc removal by O-GlcNAcase (OGA)	165:201	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	4	58	theme	physical	844:851	arg1	interactions					853:864	physical interactions	844:864	physical interactions of GATA-1 with both OGT and OGA	844:896	We observed that during G1E-ER4 differentiation, overall O-GlcNAc levels decrease, and physical interactions of GATA-1 with both OGT and OGA increase.
30523150	7	59	theme	cells	1381:1385	arg1	differentiation					1326:1340	differentiation	1326:1340	differentiation of NB4 and HL60 human myeloid leukemia cells	1326:1385	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	7	60	theme	myeloid	1364:1370	arg1	cells					1381:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	1	61	from	levels	233:238	arg1	proteins					252:259	cellular proteins	243:259	cellular proteins	243:259	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	5	62	theme	GATA-1	1068:1073	arg1	genes					1082:1086	433 GATA-1 target genes	1064:1086	433 GATA-1 target genes	1064:1086	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	3	63	theme	transcription	591:603	arg1	GATA-1					636:641	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1)	568:642	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER)	568:685	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	7	64	theme	HL60	1353:1356	arg1	cells					1381:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	NB4 and HL60 human myeloid leukemia cells	1345:1385	TMG also reduced the expression of genes involved in differentiation of NB4 and HL60 human myeloid leukemia cells, suggesting that O-GlcNAcylation is involved in the regulation of hematopoietic differentiation.
30523150	5	65	theme	genes	1082:1086	arg1	expression					1050:1059	expression	1050:1059	expression of 433 GATA-1 target genes	1050:1086	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	1	66	theme	sugar	114:118	arg1	addition					82:89	The addition	78:89	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT)	78:159	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	1	66	theme	sugar	114:118	arg1	removal					174:180	O-GlcNAc removal	165:180	O-GlcNAc removal by O-GlcNAcase (OGA)	165:201	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	9	67	from	alterations	1661:1671	arg1	O-GlcNAcylation					1676:1690	O-GlcNAcylation	1676:1690	O-GlcNAcylation	1676:1690	Our results show that alterations in O-GlcNAcylation disrupt transcriptional programs controlling erythropoietic lineage commitment, suggesting a role for O-GlcNAcylation in regulating hematopoietic cell fate.
30523150	6	68	theme	GATA-binding	1190:1201	arg1	site					1203:1206	the GATA-binding site	1186:1206	the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1186:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	6	68	theme	GATA-binding	1190:1201	arg1	promoter					1263:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	the lysosomal protein transmembrane 5 (Laptm5) gene promoter	1211:1270	ChIP results indicated that the TMG treatment decreases the occupancy of GATA-1, OGT, and OGA at the GATA-binding site of the lysosomal protein transmembrane 5 (Laptm5) gene promoter.
30523150	5	69	theme	transcriptome	922:934	arg1	analysis					936:943	RNA-Seq-based transcriptome analysis	908:943	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG)	908:1028	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	3	70	theme	GATA-binding	612:623	arg1	GATA-1					636:641	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1)	568:642	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER)	568:685	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	8	71	theme	Sustained	1484:1492	arg1	treatment					1494:1502	Sustained treatment	1484:1502	Sustained treatment of G1E-ER4 cells with TMG before differentiation	1484:1551	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	5	72	from	changes	1039:1045	arg1	expression					1050:1059	expression	1050:1059	expression of 433 GATA-1 target genes	1050:1086	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	9	73	theme	cell	1838:1841	arg1	fate					1843:1846	hematopoietic cell fate	1824:1846	hematopoietic cell fate	1824:1846	Our results show that alterations in O-GlcNAcylation disrupt transcriptional programs controlling erythropoietic lineage commitment, suggesting a role for O-GlcNAcylation in regulating hematopoietic cell fate.
30523150	8	74	theme	cells	1515:1519	arg1	treatment					1494:1502	Sustained treatment	1484:1502	Sustained treatment of G1E-ER4 cells with TMG before differentiation	1484:1551	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	8	75	with	treatment	1494:1502	arg1	TMG					1526:1528	TMG	1526:1528	TMG	1526:1528	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	1	76	theme	single	96:101	arg1	O-GlcNAc					121:128	O-GlcNAc	121:128	O-GlcNAc	121:128	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	1	76	theme	single	96:101	arg1	sugar					114:118	a single β-d-GlcNAc sugar	94:118	a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT)	94:159	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
30523150	2	77	theme	blood	425:429	arg1	formation					436:444	blood cell formation	425:444	blood cell formation	425:444	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	3	78	contain	carry	562:566	arg2	GATA-1					636:641	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1)	568:642	the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER)	568:685	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	3	78	contain	carry	562:566	arg1	cells					549:553	G1E-ER4 cells	541:553	G1E-ER4 cells	541:553	Here, we investigated the role of O-GlcNAcylation in erythropoiesis by using G1E-ER4 cells, which carry the erythroid-specific transcription factor GATA-binding protein 1 (GATA-1) fused to the estrogen receptor (GATA-1-ER) and therefore undergo erythropoiesis after β-estradiol (E2) addition.
30523150	0	79	theme	fate	41:44	arg1	decisions					46:54	cell fate decisions	36:54	cell fate decisions	36:54	O-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis.
30523150	4	80	theme	overall	806:812	arg1	levels					823:828	overall O-GlcNAc levels	806:828	overall O-GlcNAc levels	806:828	We observed that during G1E-ER4 differentiation, overall O-GlcNAc levels decrease, and physical interactions of GATA-1 with both OGT and OGA increase.
30523150	8	81	theme	stem/progenitor	1601:1615	arg1	markers					1630:1636	increased stem/progenitor cell surface markers	1591:1636	increased stem/progenitor cell surface markers	1591:1636	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	2	82	theme	fate	340:343	arg1	decisions					345:353	cell fate decisions	335:353	cell fate decisions	335:353	Changes in protein O-GlcNAcylation regulate cellular differentiation and cell fate decisions, but how these changes affect erythropoiesis, an essential process in blood cell formation, remains unclear.
30523150	8	83	theme	surface	1622:1628	arg1	markers					1630:1636	increased stem/progenitor cell surface markers	1591:1636	increased stem/progenitor cell surface markers	1591:1636	Sustained treatment of G1E-ER4 cells with TMG before differentiation reduced hemoglobin-positive cells and increased stem/progenitor cell surface markers.
30523150	5	84	theme	inhibitor	1004:1012	arg1	TMG					1025:1027	TMG	1025:1027	TMG	1025:1027	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	5	84	theme	inhibitor	1004:1012	arg1	Thiamet-G					1014:1022	the OGA inhibitor Thiamet-G	996:1022	the OGA inhibitor Thiamet-G (TMG)	996:1028	RNA-Seq-based transcriptome analysis of G1E-ER4 cells differentiated in the presence of the OGA inhibitor Thiamet-G (TMG) revealed changes in expression of 433 GATA-1 target genes.
30523150	1	85	theme	O-GlcNAc	224:231	arg1	levels					233:238	homeostatic O-GlcNAc levels	212:238	homeostatic O-GlcNAc levels on cellular proteins	212:259	The addition of a single β-d-GlcNAc sugar (O-GlcNAc) by O-GlcNAc-transferase (OGT) and O-GlcNAc removal by O-GlcNAcase (OGA) maintain homeostatic O-GlcNAc levels on cellular proteins.
31380292	8	0	theme	AP3	1142:1144	arg1	inability					1129:1137	The inability	1125:1137	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA	1125:1216	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	8	1	theme	Galf	1233:1236	arg1	part					1251:1254	part	1251:1254	part of the epitope	1251:1269	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	8	1	theme	Galf	1233:1236	arg1	residues					1238:1245	Galf residues	1233:1245	Galf residues	1233:1245	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	8	2	dep	A.	1158:1159	arg1	fumigatus					1161:1169	fumigatus	1161:1169	fumigatus	1161:1169	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	10	3	theme	longer	1518:1523	arg1	chains					1525:1530	longer chains	1518:1530	longer chains	1518:1530	Glycoarray analysis revealed that AP3 recognizes oligo-[β-D-Galf-1,5] sequences containing four or more residues with longer chains more efficiently.
31380292	3	4	theme	antibodies	468:477	arg1	use					450:452	the use	446:452	the use of monoclonal antibodies (mAbs) for the diagnosis of IA	446:508	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	9	5	theme	Several	1272:1278	arg1	lines					1280:1284	Several lines	1272:1284	Several lines of evidence	1272:1296	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	7	6	theme	culture	1109:1115	arg1	medium					1117:1122	the culture medium	1105:1122	the culture medium	1105:1122	Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium.
31380292	9	7	from	residues	1346:1353	arg1	proteins					1390:1397	Aspergillus proteins	1378:1397	Aspergillus proteins	1378:1397	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	5	8	theme	Aspergillus-specific	697:716	arg1	AP3					722:724	the Aspergillus-specific mAb AP3	693:724	the Aspergillus-specific mAb AP3 (IgG1κ)	693:732	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	5	8	theme	Aspergillus-specific	697:716	arg1	IgG1κ					727:731	IgG1κ	727:731	IgG1κ	727:731	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	5	9	theme	mAb	718:720	arg1	AP3					722:724	the Aspergillus-specific mAb AP3	693:724	the Aspergillus-specific mAb AP3 (IgG1κ)	693:732	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	5	9	theme	mAb	718:720	arg1	IgG1κ					727:731	IgG1κ	727:731	IgG1κ	727:731	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	3	10	theme	IA	507:508	arg1	diagnosis					494:502	the diagnosis	490:502	the diagnosis of IA	490:508	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	5	11	theme	AP3	722:724	arg1	characterization					673:688	the characterization	669:688	the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen	669:799	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	9	12	theme	Aspergillus	1378:1388	arg1	proteins					1390:1397	Aspergillus proteins	1378:1397	Aspergillus proteins	1378:1397	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	8	13	theme	A.	1158:1159	arg1	ΔglfA					1212:1216	the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA	1154:1216	the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA	1154:1216	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	8	14	theme	epitope	1263:1269	arg1	part					1251:1254	part	1251:1254	part of the epitope	1251:1269	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	8	14	theme	epitope	1263:1269	arg1	residues					1238:1245	Galf residues	1233:1245	Galf residues	1233:1245	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	2	15	dep	application	343:353	arg1	prompt					336:341	prompt	336:341	prompt	336:341	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	2	16	theme	therapy	379:385	arg1	application					343:353	the prompt application	332:353	the prompt application of effective antifungal therapy	332:385	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	8	17	theme	mutant	1205:1210	arg1	ΔglfA					1212:1216	the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA	1154:1216	the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA	1154:1216	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	2	18	theme	Early	254:258	arg1	detection					260:268	Early detection	254:268	Early detection of the circulating antigen galactomannan (GM) in serum	254:323	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	2	19	theme	antifungal	368:377	arg1	therapy					379:385	effective antifungal therapy	358:385	effective antifungal therapy	358:385	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	0	20	theme	Antibody	11:18	arg1	AP3					20:22	Monoclonal Antibody AP3	0:22	Monoclonal Antibody AP3	0:22	Monoclonal Antibody AP3 Binds Galactomannan Antigens Displayed by the Pathogens Aspergillus flavus, A. fumigatus, and A. parasiticus.
31380292	6	21	theme	wall	855:858	arg1	fragments					860:868	A. parasiticus cell wall fragments	835:868	A. parasiticus cell wall fragments	835:868	The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species.
31380292	7	22	theme	Immunofluorescence	921:938	arg1	microscopy					940:949	Immunofluorescence microscopy	921:949	Immunofluorescence microscopy	921:949	Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium.
31380292	9	23	theme	evidence	1289:1296	arg1	lines					1280:1284	Several lines	1272:1284	Several lines of evidence	1272:1296	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	2	24	theme	effective	358:366	arg1	therapy					379:385	effective antifungal therapy	358:385	effective antifungal therapy	358:385	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	0	25	theme	Monoclonal	0:9	arg1	Antibody					11:18	Monoclonal Antibody	0:18	Monoclonal Antibody AP3	0:22	Monoclonal Antibody AP3 Binds Galactomannan Antigens Displayed by the Pathogens Aspergillus flavus, A. fumigatus, and A. parasiticus.
31380292	10	26	theme	Glycoarray	1400:1409	arg1	analysis					1411:1418	Glycoarray analysis	1400:1418	Glycoarray analysis	1400:1418	Glycoarray analysis revealed that AP3 recognizes oligo-[β-D-Galf-1,5] sequences containing four or more residues with longer chains more efficiently.
31380292	2	27	theme	galactomannan	297:309	arg1	detection					260:268	Early detection	254:268	Early detection of the circulating antigen galactomannan (GM) in serum	254:323	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	1	28	theme	fungal	178:183	arg1	fumigatus					146:154	Aspergillus fumigatus	134:154	Aspergillus fumigatus	134:154	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	1	28	theme	fungal	178:183	arg1	flavus					163:168	A. flavus	160:168	A. flavus	160:168	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	1	28	theme	fungal	178:183	arg1	pathogens					185:193	the fungal pathogens	174:193	the fungal pathogens responsible for most cases of invasive aspergillosis (IA)	174:251	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	5	29	theme	antigen	793:799	arg1	identification					757:770	the precise identification	745:770	the precise identification of its corresponding antigen	745:799	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	5	30	theme	corresponding	779:791	arg1	antigen					793:799	its corresponding antigen	775:799	its corresponding antigen	775:799	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	2	31	theme	antigen	289:295	arg1	GM					312:313	GM	312:313	GM	312:313	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	2	31	theme	antigen	289:295	arg1	galactomannan					297:309	the circulating antigen galactomannan	273:309	the circulating antigen galactomannan (GM)	273:314	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	9	32	theme	O-linked	1358:1365	arg1	glycans					1367:1373	O-linked glycans	1358:1373	O-linked glycans	1358:1373	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	2	33	theme	survival	407:414	arg1	rate					416:419	the survival rate	403:419	the survival rate of IA patients	403:434	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	6	34	theme	cell	850:853	arg1	fragments					860:868	A. parasiticus cell wall fragments	835:868	A. parasiticus cell wall fragments	835:868	The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species.
31380292	2	35	theme	circulating	277:287	arg1	GM					312:313	GM	312:313	GM	312:313	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	2	35	theme	circulating	277:287	arg1	galactomannan					297:309	the circulating antigen galactomannan	273:309	the circulating antigen galactomannan (GM)	273:314	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	1	36	theme	responsible	195:205	arg1	fumigatus					146:154	Aspergillus fumigatus	134:154	Aspergillus fumigatus	134:154	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	1	36	theme	responsible	195:205	arg1	flavus					163:168	A. flavus	160:168	A. flavus	160:168	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	1	36	theme	responsible	195:205	arg1	pathogens					185:193	the fungal pathogens	174:193	the fungal pathogens responsible for most cases of invasive aspergillosis (IA)	174:251	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	8	37	theme	-deficient	1194:1203	arg1	ΔglfA					1212:1216	the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA	1154:1216	the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA	1154:1216	The inability of AP3 to bind the A. fumigatus galactofuranose (Galf )-deficient mutant ΔglfA confirmed that Galf residues are part of the epitope.
31380292	7	38	link	enzyme-linked	1024:1036	arg1	assays					1052:1057	enzyme-linked immunosorbent assays	1024:1057	enzyme-linked immunosorbent assays	1024:1057	Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium.
31380292	6	39	theme	parasiticus	838:848	arg1	fragments					860:868	A. parasiticus cell wall fragments	835:868	A. parasiticus cell wall fragments	835:868	The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species.
31380292	7	40	dep	enzyme-linked	1024:1036	arg1	immunosorbent					1038:1050	immunosorbent	1038:1050	immunosorbent	1038:1050	Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium.
31380292	4	41	theme	specific	610:617	arg1	antibodies					619:628	More specific antibodies	605:628	More specific antibodies	605:628	More specific antibodies are therefore needed.
31380292	0	42	theme	Galactomannan	30:42	arg1	Antigens					44:51	Galactomannan Antigens	30:51	Galactomannan Antigens Displayed by the Pathogens Aspergillus flavus, A. fumigatus, and A. parasiticus	30:131	Monoclonal Antibody AP3 Binds Galactomannan Antigens Displayed by the Pathogens Aspergillus flavus, A. fumigatus, and A. parasiticus.
31380292	9	43	theme	Galf	1341:1344	arg1	residues					1346:1353	the Galf residues	1337:1353	the Galf residues of O-linked glycans on Aspergillus proteins	1337:1397	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	9	43	theme	Galf	1341:1344	arg1	glycans					1367:1373	O-linked glycans	1358:1373	O-linked glycans	1358:1373	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	5	44	theme	precise	749:755	arg1	identification					757:770	the precise identification	745:770	the precise identification of its corresponding antigen	745:799	Here we describe the characterization of the Aspergillus-specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen.
31380292	6	45	theme	A.	835:836	arg1	fragments					860:868	A. parasiticus cell wall fragments	835:868	A. parasiticus cell wall fragments	835:868	The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species.
31380292	3	46	theme	due	551:553	arg1	positives					541:549	false positives	535:549	false positives due to cross-reaction with bacterial polysaccharides	535:602	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	1	47	theme	most	211:214	arg1	cases					216:220	most cases	211:220	most cases of invasive aspergillosis (IA)	211:251	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	10	48	contain	containing	1480:1489	arg1	sequences					1470:1478	oligo-[β-D-Galf-1,5] sequences	1449:1478	oligo-[β-D-Galf-1,5] sequences containing four or more residues with longer chains	1449:1530	Glycoarray analysis revealed that AP3 recognizes oligo-[β-D-Galf-1,5] sequences containing four or more residues with longer chains more efficiently.
31380292	10	48	contain	containing	1480:1489	arg2	residues					1504:1511	four or more residues	1491:1511	four or more residues	1491:1511	Glycoarray analysis revealed that AP3 recognizes oligo-[β-D-Galf-1,5] sequences containing four or more residues with longer chains more efficiently.
31380292	9	49	link	O-linked	1358:1365	arg1	glycans					1367:1373	O-linked glycans	1358:1373	O-linked glycans	1358:1373	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	2	50	theme	patients	427:434	arg1	rate					416:419	the survival rate	403:419	the survival rate of IA patients	403:434	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	11	51	theme	diagnostic	1629:1638	arg1	tool					1640:1643	a diagnostic tool	1627:1643	a diagnostic tool for patients with IA	1627:1664	We also showed that AP3 captures GM in serum, suggesting it may be useful as a diagnostic tool for patients with IA.
31380292	3	52	theme	false	535:539	arg1	positives					541:549	false positives	535:549	false positives due to cross-reaction with bacterial polysaccharides	535:602	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	3	53	theme	monoclonal	457:466	arg1	mAbs					480:483	mAbs	480:483	mAbs	480:483	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	3	53	theme	monoclonal	457:466	arg1	antibodies					468:477	monoclonal antibodies	457:477	monoclonal antibodies (mAbs)	457:484	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	2	54	from	detection	260:268	arg1	serum					319:323	serum	319:323	serum	319:323	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	6	55	theme	Aspergillus	900:910	arg1	species					912:918	several Aspergillus species	892:918	several Aspergillus species	892:918	The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species.
31380292	0	56	dep	Pathogens	70:78	arg1	parasiticus					121:131	A. parasiticus	118:131	A. parasiticus	118:131	Monoclonal Antibody AP3 Binds Galactomannan Antigens Displayed by the Pathogens Aspergillus flavus, A. fumigatus, and A. parasiticus.
31380292	0	56	dep	Pathogens	70:78	arg1	flavus					92:97	Aspergillus flavus	80:97	Aspergillus flavus	80:97	Monoclonal Antibody AP3 Binds Galactomannan Antigens Displayed by the Pathogens Aspergillus flavus, A. fumigatus, and A. parasiticus.
31380292	0	56	dep	Pathogens	70:78	arg1	fumigatus					103:111	A. fumigatus	100:111	A. fumigatus	100:111	Monoclonal Antibody AP3 Binds Galactomannan Antigens Displayed by the Pathogens Aspergillus flavus, A. fumigatus, and A. parasiticus.
31380292	9	57	theme	glycans	1367:1373	arg1	residues					1346:1353	the Galf residues	1337:1353	the Galf residues of O-linked glycans on Aspergillus proteins	1337:1397	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	9	57	theme	glycans	1367:1373	arg1	glycans					1367:1373	O-linked glycans	1358:1373	O-linked glycans	1358:1373	Several lines of evidence strongly indicated that AP3 recognizes the Galf residues of O-linked glycans on Aspergillus proteins.
31380292	7	58	theme	enzyme-linked	1024:1036	arg1	assays					1052:1057	enzyme-linked immunosorbent assays	1024:1057	enzyme-linked immunosorbent assays	1024:1057	Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium.
31380292	3	59	theme	bacterial	578:586	arg1	polysaccharides					588:602	bacterial polysaccharides	578:602	bacterial polysaccharides	578:602	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	7	60	theme	cell	977:980	arg1	antigen					987:993	a cell wall antigen	975:993	a cell wall antigen	975:993	Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium.
31380292	7	61	theme	wall	982:985	arg1	antigen					987:993	a cell wall antigen	975:993	a cell wall antigen	975:993	Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium.
31380292	11	62	with	patients	1649:1656	arg1	IA					1663:1664	IA	1663:1664	IA	1663:1664	We also showed that AP3 captures GM in serum, suggesting it may be useful as a diagnostic tool for patients with IA.
31380292	1	63	theme	invasive	225:232	arg1	IA					249:250	IA	249:250	IA	249:250	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	1	63	theme	invasive	225:232	arg1	aspergillosis					234:246	invasive aspergillosis	225:246	invasive aspergillosis (IA)	225:251	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
31380292	3	64	with	cross-reaction	558:571	arg1	polysaccharides					588:602	bacterial polysaccharides	578:602	bacterial polysaccharides	578:602	However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides.
31380292	6	65	theme	several	892:898	arg1	species					912:918	several Aspergillus species	892:918	several Aspergillus species	892:918	The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species.
31380292	2	66	theme	IA	424:425	arg1	patients					427:434	IA patients	424:434	IA patients	424:434	Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients.
31380292	1	67	theme	aspergillosis	234:246	arg1	cases					216:220	most cases	211:220	most cases of invasive aspergillosis (IA)	211:251	Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA).
30762425	6	0	theme	expression	1273:1282	arg1	downregulation					1250:1263	the downregulation	1246:1263	the downregulation of UAP1 expression	1246:1282	Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression.
30762425	4	1	theme	protein	888:894	arg1	expression					896:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	5	2	from	induction	1072:1080	arg1	HEP-G2					1098:1103	HEP-G2	1098:1103	HEP-G2	1098:1103	Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells.
30762425	5	2	from	induction	1072:1080	arg1	cells					1115:1119	HuH-7 cells	1109:1119	HuH-7 cells	1109:1119	Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells.
30762425	4	3	theme	expression	896:905	arg1	upregulation					796:807	upregulation	796:807	upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	796:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	4	3	theme	expression	896:905	arg1	stability					916:924	protein stability	908:924	protein stability	908:924	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	4	3	theme	expression	896:905	arg1	inhibition					931:940	inhibition	931:940	inhibition of its ubiquitination	931:962	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	0	4	theme	Liver	113:117	arg1	Cancer					119:124	Liver Cancer	113:124	Liver Cancer	113:124	Reciprocal Regulation Between O-GlcNAcylation and β-Catenin Facilitates Cell Viability and Inhibits Apoptosis in Liver Cancer.
30762425	1	5	theme	cancer	230:235	arg1	feature					219:225	a general feature	209:225	a general feature of cancer	209:235	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	1	5	theme	cancer	230:235	arg1	expression					136:145	Abnormal expression	127:145	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin	127:204	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	7	6	theme	liver	1422:1426	arg1	cancer					1428:1433	liver cancer	1422:1433	liver cancer	1422:1433	In conclusion, this study revealed that the reciprocal regulation between O-GlcNAcylation and β-catenin facilitated the proliferation of liver cancer.
30762425	4	7	theme	expression	770:779	arg1	levels					781:786	O-GlcNAc expression levels	761:786	O-GlcNAc expression levels	761:786	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	3	8	from	accumulation	643:654	arg1	HuH-7					698:702	HuH-7	698:702	HuH-7	698:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	8	from	accumulation	643:654	arg1	HEP-G2					687:692	HEP-G2	687:692	HEP-G2	687:692	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	8	from	accumulation	643:654	arg1	lines					681:685	the liver cancer cell lines	659:685	the liver cancer cell lines HEP-G2 and HuH-7	659:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	4	9	theme	O-GlcNAc	761:768	arg1	levels					781:786	O-GlcNAc expression levels	761:786	O-GlcNAc expression levels	761:786	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	3	10	theme	β-catenin	559:567	arg1	levels					588:593	β-catenin protein expression levels	559:593	β-catenin protein expression levels	559:593	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	11	dep	lines	681:685	arg1	HuH-7					698:702	HuH-7	698:702	HuH-7	698:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	11	dep	lines	681:685	arg1	HEP-G2					687:692	HEP-G2	687:692	HEP-G2	687:692	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	11	dep	lines	681:685	arg1	lines					681:685	the liver cancer cell lines	659:685	the liver cancer cell lines HEP-G2 and HuH-7	659:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	5	12	theme	β-catenin	998:1006	arg1	O-GlcNAcylation					979:993	the O-GlcNAcylation	975:993	the O-GlcNAcylation of β-catenin	975:1006	Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells.
30762425	2	13	theme	liver	406:410	arg1	cancer					412:417	liver cancer	406:417	liver cancer	406:417	In this study, we identified the interaction between O-GlcNAc and β-catenin, and explored their effects on the progression of liver cancer.
30762425	4	14	theme	pyrophosphorylase	861:877	arg1	expression					896:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	3	15	theme	GlcNAc	542:547	arg1	application					516:526	the application	512:526	the application of PuGNAc and GlcNAc	512:547	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	16	from	stability	621:629	arg1	HuH-7					698:702	HuH-7	698:702	HuH-7	698:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	16	from	stability	621:629	arg1	HEP-G2					687:692	HEP-G2	687:692	HEP-G2	687:692	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	16	from	stability	621:629	arg1	lines					681:685	the liver cancer cell lines	659:685	the liver cancer cell lines HEP-G2 and HuH-7	659:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	1	17	theme	β-catenin	196:204	arg1	feature					219:225	a general feature	209:225	a general feature of cancer	209:235	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	1	17	theme	β-catenin	196:204	arg1	expression					136:145	Abnormal expression	127:145	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin	127:204	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	4	18	theme	UAP1	882:885	arg1	expression					896:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	4	19	theme	β-catenin	736:744	arg1	overexpression					718:731	overexpression	718:731	overexpression of β-catenin	718:744	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	0	20	theme	Reciprocal	0:9	arg1	Regulation					11:20	Reciprocal Regulation	0:20	Reciprocal Regulation Between O-GlcNAcylation and β-Catenin	0:58	Reciprocal Regulation Between O-GlcNAcylation and β-Catenin Facilitates Cell Viability and Inhibits Apoptosis in Liver Cancer.
30762425	5	21	theme	apoptosis	1085:1093	arg1	induction					1072:1080	the induction	1068:1080	the induction of apoptosis in HEP-G2 and HuH-7 cells	1068:1119	Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells.
30762425	6	22	theme	cell	1223:1226	arg1	apoptosis					1228:1236	cell apoptosis	1223:1236	cell apoptosis	1223:1236	Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression.
30762425	2	23	from	effects	376:382	arg1	progression					391:401	the progression	387:401	the progression of liver cancer	387:417	In this study, we identified the interaction between O-GlcNAc and β-catenin, and explored their effects on the progression of liver cancer.
30762425	3	24	theme	protein	569:575	arg1	levels					588:593	β-catenin protein expression levels	559:593	β-catenin protein expression levels	559:593	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	6	25	theme	UAP1	1268:1271	arg1	expression					1273:1282	UAP1 expression	1268:1282	UAP1 expression	1268:1282	Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression.
30762425	1	26	theme	general	211:217	arg1	feature					219:225	a general feature	209:225	a general feature of cancer	209:235	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	1	26	theme	general	211:217	arg1	expression					136:145	Abnormal expression	127:145	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin	127:204	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	6	27	theme	β-catenin	1135:1143	arg1	Knockdown					1122:1130	Knockdown	1122:1130	Knockdown of β-catenin	1122:1143	Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression.
30762425	0	28	from	Apoptosis	100:108	arg1	Cancer					119:124	Liver Cancer	113:124	Liver Cancer	113:124	Reciprocal Regulation Between O-GlcNAcylation and β-Catenin Facilitates Cell Viability and Inhibits Apoptosis in Liver Cancer.
30762425	3	29	theme	expression	577:586	arg1	levels					588:593	β-catenin protein expression levels	559:593	β-catenin protein expression levels	559:593	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	4	30	theme	ubiquitination	949:962	arg1	upregulation					796:807	upregulation	796:807	upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	796:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	4	30	theme	ubiquitination	949:962	arg1	stability					916:924	protein stability	908:924	protein stability	908:924	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	4	30	theme	ubiquitination	949:962	arg1	inhibition					931:940	inhibition	931:940	inhibition of its ubiquitination	931:962	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	3	31	dep	stability	621:629	arg1	the					607:609	the	607:609	the	607:609	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	4	32	theme	UDP	836:838	arg1	expression					896:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	3	33	theme	O-GlcNAc	466:473	arg1	upregulation					450:461	upregulation	450:461	upregulation of O-GlcNAc	450:473	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	34	theme	nuclear	635:641	arg1	accumulation					643:654	nuclear accumulation	635:654	nuclear accumulation	635:654	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	2	35	theme	cancer	412:417	arg1	progression					391:401	the progression	387:401	the progression of liver cancer	387:417	In this study, we identified the interaction between O-GlcNAc and β-catenin, and explored their effects on the progression of liver cancer.
30762425	0	36	theme	Cell	72:75	arg1	Viability					77:85	Cell Viability	72:85	Cell Viability	72:85	Reciprocal Regulation Between O-GlcNAcylation and β-Catenin Facilitates Cell Viability and Inhibits Apoptosis in Liver Cancer.
30762425	5	37	theme	HuH-7	1109:1113	arg1	cells					1115:1119	HuH-7 cells	1109:1119	HuH-7 cells	1109:1119	Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells.
30762425	4	38	theme	-N-acetylglucosamine	840:859	arg1	expression					896:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	1	39	theme	Abnormal	127:134	arg1	feature					219:225	a general feature	209:225	a general feature of cancer	209:235	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	1	39	theme	Abnormal	127:134	arg1	expression					136:145	Abnormal expression	127:145	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin	127:204	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	4	40	theme	protein	908:914	arg1	stability					916:924	protein stability	908:924	protein stability	908:924	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	3	41	theme	cell	676:679	arg1	HuH-7					698:702	HuH-7	698:702	HuH-7	698:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	41	theme	cell	676:679	arg1	HEP-G2					687:692	HEP-G2	687:692	HEP-G2	687:692	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	41	theme	cell	676:679	arg1	lines					681:685	the liver cancer cell lines	659:685	the liver cancer cell lines HEP-G2 and HuH-7	659:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	7	42	theme	cancer	1428:1433	arg1	proliferation					1405:1417	the proliferation	1401:1417	the proliferation of liver cancer	1401:1433	In conclusion, this study revealed that the reciprocal regulation between O-GlcNAcylation and β-catenin facilitated the proliferation of liver cancer.
30762425	6	43	theme	cell	1153:1156	arg1	proliferation					1158:1170	cell proliferation	1153:1170	cell proliferation	1153:1170	Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression.
30762425	5	44	theme	colony	1036:1041	arg1	proliferation					1021:1033	the proliferation	1017:1033	the proliferation	1017:1033	Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells.
30762425	5	44	theme	colony	1036:1041	arg1	formation					1043:1051	colony formation	1036:1051	colony formation	1036:1051	Moreover, the O-GlcNAcylation of β-catenin promoted the proliferation, colony formation, and repressed the induction of apoptosis in HEP-G2 and HuH-7 cells.
30762425	3	45	theme	high	490:493	arg1	glucose					495:501	high glucose	490:501	high glucose	490:501	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	6	46	theme	colony	1173:1178	arg1	formation					1180:1188	colony formation	1173:1188	colony formation	1173:1188	Knockdown of β-catenin reduced cell proliferation, colony formation, and tumorigenesis, and promoted cell apoptosis through the downregulation of UAP1 expression.
30762425	3	47	theme	liver	663:667	arg1	HuH-7					698:702	HuH-7	698:702	HuH-7	698:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	47	theme	liver	663:667	arg1	HEP-G2					687:692	HEP-G2	687:692	HEP-G2	687:692	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	47	theme	liver	663:667	arg1	lines					681:685	the liver cancer cell lines	659:685	the liver cancer cell lines HEP-G2 and HuH-7	659:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	1	48	theme	O-Linked	150:157	arg1	O-GlcNAc					182:189	O-GlcNAc	182:189	O-GlcNAc	182:189	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	1	48	theme	O-Linked	150:157	arg1	β-N-acetylglucosamine					159:179	O-Linked β-N-acetylglucosamine	150:179	O-Linked β-N-acetylglucosamine (O-GlcNAc)	150:190	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	3	49	from	levels	588:593	arg1	HuH-7					698:702	HuH-7	698:702	HuH-7	698:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	49	from	levels	588:593	arg1	HEP-G2					687:692	HEP-G2	687:692	HEP-G2	687:692	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	49	from	levels	588:593	arg1	lines					681:685	the liver cancer cell lines	659:685	the liver cancer cell lines HEP-G2 and HuH-7	659:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	50	theme	cancer	669:674	arg1	HuH-7					698:702	HuH-7	698:702	HuH-7	698:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	50	theme	cancer	669:674	arg1	HEP-G2					687:692	HEP-G2	687:692	HEP-G2	687:692	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	3	50	theme	cancer	669:674	arg1	lines					681:685	the liver cancer cell lines	659:685	the liver cancer cell lines HEP-G2 and HuH-7	659:702	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	4	51	theme	5'-diphosphate	820:833	arg1	expression					896:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	7	52	theme	reciprocal	1329:1338	arg1	regulation					1340:1349	the reciprocal regulation	1325:1349	the reciprocal regulation between O-GlcNAcylation and β-catenin	1325:1387	In conclusion, this study revealed that the reciprocal regulation between O-GlcNAcylation and β-catenin facilitated the proliferation of liver cancer.
30762425	1	53	theme	β-N-acetylglucosamine	159:179	arg1	feature					219:225	a general feature	209:225	a general feature of cancer	209:235	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	1	53	theme	β-N-acetylglucosamine	159:179	arg1	expression					136:145	Abnormal expression	127:145	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin	127:204	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30762425	4	54	theme	uridine	812:818	arg1	expression					896:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression	812:905	In addition, overexpression of β-catenin could increase O-GlcNAc expression levels through upregulation of uridine 5'-diphosphate (UDP)-N-acetylglucosamine pyrophosphorylase 1 (UAP1) protein expression, protein stability, and inhibition of its ubiquitination.
30762425	3	55	theme	PuGNAc	531:536	arg1	application					516:526	the application	512:526	the application of PuGNAc and GlcNAc	512:547	Our results demonstrated that upregulation of O-GlcNAc was induced by high glucose, whereas the application of PuGNAc and GlcNAc increased β-catenin protein expression levels, as well as the protein's stability and nuclear accumulation in the liver cancer cell lines HEP-G2 and HuH-7.
30762425	1	56	theme	transformed	256:266	arg1	phenotypes					268:277	transformed phenotypes	256:277	transformed phenotypes	256:277	Abnormal expression of O-Linked β-N-acetylglucosamine (O-GlcNAc) and β-catenin is a general feature of cancer and contributes to transformed phenotypes.
30735356	0	0	theme	Cellular	78:85	arg1	Attachment					87:96	Cellular Attachment	78:96	Cellular Attachment	78:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	5	1	theme	region	928:933	arg1	absence					902:908	absence	902:908	absence of the mucin-like region	902:933	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	8	2	theme	new	1338:1340	arg1	evidence					1342:1349	new evidence	1338:1349	new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans	1338:1447	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	1	3	theme	viruses	238:244	arg1	glycoproteins					216:228	the viral envelope glycoproteins	197:228	the viral envelope glycoproteins of many viruses	197:244	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	7	4	gly	glycoproteins	1241:1253	arg1	glycoproteins					1241:1253	glycoproteins	1241:1253	glycoproteins involved in the virus-glycosaminoglycan interaction	1241:1305	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	0	5	from	Mechanisms	11:20	arg1	Virus					65:69	Herpes Simplex Virus	50:69	Herpes Simplex Virus during Cellular Attachment	50:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	1	6	link	O-linked	160:167	arg1	glycosylation					169:181	O-linked glycosylation	160:181	O-linked glycosylation	160:181	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	1	7	gly	glycoproteins	216:228	arg1	glycoproteins					216:228	the viral envelope glycoproteins	197:228	the viral envelope glycoproteins of many viruses	197:244	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	2	8	theme	mucin-like	308:317	arg1	region					319:324	a mucin-like region	306:324	a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans	306:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	8	9	theme	HSV-1	1419:1423	arg1	interaction					1404:1414	the interaction	1400:1414	the interaction of HSV-1 with glycosaminoglycans	1400:1447	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	4	10	theme	molecular	702:710	arg1	mechanisms					712:721	the molecular mechanisms	698:721	the molecular mechanisms	698:721	However, the molecular mechanisms and the role as a pathogenicity factor remains unclear.
30735356	8	11	theme	mucin-like	1369:1378	arg1	region					1380:1385	the mucin-like region	1365:1385	the mucin-like region	1365:1385	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	7	12	theme	glycoproteins	1241:1253	arg1	number					1231:1236	number	1231:1236	number	1231:1236	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	7	12	theme	glycoproteins	1241:1253	arg1	affinity					1211:1218	affinity	1211:1218	affinity	1211:1218	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	7	12	theme	glycoproteins	1241:1253	arg1	type					1221:1224	type	1221:1224	type	1221:1224	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	3	13	theme	mucin-like	494:503	arg1	region					505:510	this mucin-like region	489:510	this mucin-like region	489:510	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	5	14	theme	particle	798:805	arg1	tracking					807:814	single virus particle tracking	785:814	single virus particle tracking	785:814	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	7	15	theme	virus-glycosaminoglycan	1156:1178	arg1	interactions					1180:1191	virus-glycosaminoglycan interactions	1156:1191	virus-glycosaminoglycan interactions	1156:1191	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	3	16	theme	infected	673:680	arg1	cells					682:686	infected cells	673:686	infected cells	673:686	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	3	17	from	cells	682:686	arg1	release					643:649	release	643:649	release of HSV-1 virions from infected cells	643:686	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	2	18	with	interaction	435:445	arg1	glycosaminoglycans					461:478	sulfated glycosaminoglycans	452:478	sulfated glycosaminoglycans	452:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	8	19	theme	region	1380:1385	arg1	role					1357:1360	a role	1355:1360	a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans	1355:1447	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	1	20	theme	O-linked	160:167	arg1	glycosylation					169:181	O-linked glycosylation	160:181	O-linked glycosylation	160:181	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	2	21	theme	sulfated	452:459	arg1	glycosaminoglycans					461:478	sulfated glycosaminoglycans	452:478	sulfated glycosaminoglycans	452:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	0	22	from	Region	40:45	arg1	Virus					65:69	Herpes Simplex Virus	50:69	Herpes Simplex Virus during Cellular Attachment	50:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	2	23	theme	cell	418:421	arg1	surface					423:429	the cell surface	414:429	the cell surface	414:429	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	24	from	region	319:324	arg1	protein					358:364	a viral protein	350:364	a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans	350:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	24	from	region	319:324	arg1	gC					346:347	its glycoprotein gC	329:347	its glycoprotein gC	329:347	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	25	theme	virus	262:266	arg1	type					268:271	Herpes simplex virus type 1	247:273	Herpes simplex virus type 1 (HSV-1)	247:281	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	25	theme	virus	262:266	arg1	HSV-1					276:280	HSV-1	276:280	HSV-1	276:280	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	1	26	theme	glycosylation	169:181	arg1	density					149:155	a local high density	136:155	a local high density of O-linked glycosylation	136:181	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	3	27	theme	virions	660:666	arg1	release					643:649	release	643:649	release of HSV-1 virions from infected cells	643:686	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	2	28	gly	glycoprotein	333:344	arg1	glycoprotein					333:344	its glycoprotein gC	329:347	its glycoprotein gC	329:347	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	5	29	theme	virions	878:884	arg1	mobility					834:841	the mobility	830:841	the mobility of chondroitin sulfate-bound HSV-1 virions	830:884	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	6	30	theme	binding	1019:1025	arg1	forces					1027:1032	HSV-1-chondroitin sulfate binding forces	993:1032	HSV-1-chondroitin sulfate binding forces	993:1032	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	0	31	theme	Regulatory	0:9	arg1	Mechanisms					11:20	Regulatory Mechanisms	0:20	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment	0:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	8	32	with	interaction	1404:1414	arg1	glycosaminoglycans					1430:1447	glycosaminoglycans	1430:1447	glycosaminoglycans	1430:1447	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	8	33	theme	molecular	1488:1496	arg1	mechanisms					1498:1507	the molecular mechanisms	1484:1507	the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell	1484:1597	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	8	34	from	cell	1594:1597	arg1	release					1568:1574	release	1568:1574	release from the infected cell	1568:1597	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	8	34	from	cell	1594:1597	arg1	entry					1558:1562	successful cell entry	1542:1562	successful cell entry	1542:1562	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	3	35	with	interactions	567:578	arg1	glycosaminoglycans					594:611	cellular glycosaminoglycans	585:611	cellular glycosaminoglycans	585:611	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	2	36	theme	glycoprotein	333:344	arg1	protein					358:364	a viral protein	350:364	a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans	350:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	36	theme	glycoprotein	333:344	arg1	gC					346:347	its glycoprotein gC	329:347	its glycoprotein gC	329:347	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	8	37	theme	cell	1553:1556	arg1	entry					1558:1562	successful cell entry	1542:1562	successful cell entry	1542:1562	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	1	38	theme	Mucin-like	99:108	arg1	regions					110:116	Mucin-like regions	99:116	Mucin-like regions	99:116	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	6	39	theme	HSV-1-chondroitin	993:1009	arg1	forces					1027:1032	HSV-1-chondroitin sulfate binding forces	993:1032	HSV-1-chondroitin sulfate binding forces	993:1032	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	2	40	theme	initial	378:384	arg1	recruitment					386:396	initial recruitment	378:396	initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans	378:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	6	41	theme	atomic	1052:1057	arg1	spectroscopy					1088:1099	atomic force microscopy-based force spectroscopy	1052:1099	atomic force microscopy-based force spectroscopy	1052:1099	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	7	42	dep	affinity	1211:1218	arg1	the					1207:1209	the	1207:1209	the	1207:1209	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	3	43	theme	cellular	585:592	arg1	glycosaminoglycans					594:611	cellular glycosaminoglycans	585:611	cellular glycosaminoglycans	585:611	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	6	44	from	decrease	941:948	arg1	mobility					953:960	mobility	953:960	mobility	953:960	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	8	45	theme	successful	1542:1551	arg1	entry					1558:1562	successful cell entry	1542:1562	successful cell entry	1542:1562	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	6	46	theme	force	1059:1063	arg1	spectroscopy					1088:1099	atomic force microscopy-based force spectroscopy	1052:1099	atomic force microscopy-based force spectroscopy	1052:1099	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	0	47	theme	Region	40:45	arg1	Mechanisms					11:20	Regulatory Mechanisms	0:20	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment	0:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	7	48	theme	virus-glycosaminoglycan	1271:1293	arg1	interaction					1295:1305	the virus-glycosaminoglycan interaction	1267:1305	the virus-glycosaminoglycan interaction	1267:1305	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	6	49	theme	sulfate	1011:1017	arg1	forces					1027:1032	HSV-1-chondroitin sulfate binding forces	993:1032	HSV-1-chondroitin sulfate binding forces	993:1032	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	5	50	theme	single	785:790	arg1	tracking					807:814	single virus particle tracking	785:814	single virus particle tracking	785:814	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	0	51	theme	Mucin-Like	29:38	arg1	Region					40:45	the Mucin-Like Region	25:45	the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment	25:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	0	52	from	Virus	65:69	arg1	Mechanisms					11:20	Regulatory Mechanisms	0:20	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment	0:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	3	53	theme	key	540:542	arg1	role					544:547	a key role	538:547	a key role	538:547	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	5	54	theme	virus	792:796	arg1	tracking					807:814	single virus particle tracking	785:814	single virus particle tracking	785:814	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	1	55	theme	viral	201:205	arg1	glycoproteins					216:228	the viral envelope glycoproteins	197:228	the viral envelope glycoproteins of many viruses	197:244	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	0	56	theme	Herpes	50:55	arg1	Virus					65:69	Herpes Simplex Virus	50:69	Herpes Simplex Virus during Cellular Attachment	50:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	8	57	theme	further	1462:1468	arg1	insights					1470:1477	further insights	1462:1477	further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell	1462:1597	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	3	58	theme	HSV-1	654:658	arg1	virions					660:666	HSV-1 virions	654:666	HSV-1 virions	654:666	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	2	59	theme	virus	405:409	arg1	recruitment					386:396	initial recruitment	378:396	initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans	378:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	5	60	theme	chondroitin	846:856	arg1	virions					878:884	chondroitin sulfate-bound HSV-1 virions	846:884	chondroitin sulfate-bound HSV-1 virions	846:884	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	8	61	theme	infected	1585:1592	arg1	cell					1594:1597	the infected cell	1581:1597	the infected cell	1581:1597	This study therefore presents new evidence for a role of the mucin-like region in balancing the interaction of HSV-1 with glycosaminoglycans and provides further insights into the molecular mechanisms used by the virus to ensure both successful cell entry and release from the infected cell.
30735356	1	62	located	found	188:192	arg2	regions					110:116	Mucin-like regions	99:116	Mucin-like regions	99:116	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	1	62	located	found	188:192	arg1	glycoproteins					216:228	the viral envelope glycoproteins	197:228	the viral envelope glycoproteins of many viruses	197:244	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	2	63	theme	simplex	254:260	arg1	type					268:271	Herpes simplex virus type 1	247:273	Herpes simplex virus type 1 (HSV-1)	247:281	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	63	theme	simplex	254:260	arg1	HSV-1					276:280	HSV-1	276:280	HSV-1	276:280	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	4	64	theme	pathogenicity	741:753	arg1	factor					755:760	a pathogenicity factor	739:760	a pathogenicity factor	739:760	However, the molecular mechanisms and the role as a pathogenicity factor remains unclear.
30735356	5	65	theme	sulfate-bound	858:870	arg1	virions					878:884	chondroitin sulfate-bound HSV-1 virions	846:884	chondroitin sulfate-bound HSV-1 virions	846:884	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	6	66	theme	microscopy-based	1065:1080	arg1	spectroscopy					1088:1099	atomic force microscopy-based force spectroscopy	1052:1099	atomic force microscopy-based force spectroscopy	1052:1099	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	1	67	theme	envelope	207:214	arg1	glycoproteins					216:228	the viral envelope glycoproteins	197:228	the viral envelope glycoproteins of many viruses	197:244	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	5	68	theme	mucin-like	917:926	arg1	region					928:933	the mucin-like region	913:933	the mucin-like region	913:933	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	2	69	theme	Herpes	247:252	arg1	type					268:271	Herpes simplex virus type 1	247:273	Herpes simplex virus type 1 (HSV-1)	247:281	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	69	theme	Herpes	247:252	arg1	HSV-1					276:280	HSV-1	276:280	HSV-1	276:280	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	5	70	theme	HSV-1	872:876	arg1	virions					878:884	chondroitin sulfate-bound HSV-1 virions	846:884	chondroitin sulfate-bound HSV-1 virions	846:884	Using single virus particle tracking, we show that the mobility of chondroitin sulfate-bound HSV-1 virions is decreased in absence of the mucin-like region.
30735356	6	71	from	increase	981:988	arg1	forces					1027:1032	HSV-1-chondroitin sulfate binding forces	993:1032	HSV-1-chondroitin sulfate binding forces	993:1032	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	6	72	theme	force	1082:1086	arg1	spectroscopy					1088:1099	atomic force microscopy-based force spectroscopy	1052:1099	atomic force microscopy-based force spectroscopy	1052:1099	This decrease in mobility correlates with an increase in HSV-1-chondroitin sulfate binding forces as observed using atomic force microscopy-based force spectroscopy.
30735356	2	73	theme	viral	352:356	arg1	protein					358:364	a viral protein	350:364	a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans	350:478	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	2	73	theme	viral	352:356	arg1	gC					346:347	its glycoprotein gC	329:347	its glycoprotein gC	329:347	Herpes simplex virus type 1 (HSV-1), for example, exhibits a mucin-like region on its glycoprotein gC, a viral protein involved in initial recruitment of the virus to the cell surface via interaction with sulfated glycosaminoglycans.
30735356	1	74	theme	local	138:142	arg1	density					149:155	a local high density	136:155	a local high density of O-linked glycosylation	136:181	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	3	75	dep	play	533:536	arg1	promote					635:641	promote	635:641	to promote release of HSV-1 virions from infected cells	632:686	So far, this mucin-like region has been proposed to play a key role in modulating the interactions with cellular glycosaminoglycans, and in particular to promote release of HSV-1 virions from infected cells.
30735356	0	76	theme	Simplex	57:63	arg1	Virus					65:69	Herpes Simplex Virus	50:69	Herpes Simplex Virus during Cellular Attachment	50:96	Regulatory Mechanisms of the Mucin-Like Region on Herpes Simplex Virus during Cellular Attachment.
30735356	7	77	theme	mucin-like	1128:1137	arg1	region					1139:1144	the mucin-like region	1124:1144	the mucin-like region	1124:1144	Our data suggest that the mucin-like region modulates virus-glycosaminoglycan interactions by regulating the affinity, type, and number of glycoproteins involved in the virus-glycosaminoglycan interaction.
30735356	1	78	theme	high	144:147	arg1	density					149:155	a local high density	136:155	a local high density of O-linked glycosylation	136:181	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30735356	1	79	theme	many	233:236	arg1	viruses					238:244	many viruses	233:244	many viruses	233:244	Mucin-like regions, characterized by a local high density of O-linked glycosylation, are found on the viral envelope glycoproteins of many viruses.
30550897	1	0	link	O-linked	97:104	arg1	enzyme					160:165	an essential enzyme	147:165	an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein	147:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	0	link	O-linked	97:104	arg1	OGT					139:141	OGT	139:141	OGT	139:141	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	0	link	O-linked	97:104	arg1	transferase					126:136	O-linked N-acetylglucosamine transferase	97:136	O-linked N-acetylglucosamine transferase (OGT)	97:142	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	7	1	theme	corresponding	1162:1174	arg1	mechanism					1176:1184	the corresponding mechanism	1158:1184	the corresponding mechanism	1158:1184	The thermodynamic and dynamic properties as along with the corresponding mechanism were determined and discussed according to the umbrella sampling technique.
30550897	6	2	theme	molecular	1007:1015	arg1	simulations					1033:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	2	3	theme	important	340:348	arg1	reactions					383:391	many important cellular physiological catalytic reactions	335:391	many important cellular physiological catalytic reactions	335:391	It plays an important role in many important cellular physiological catalytic reactions.
30550897	6	4	theme	favorable	946:954	arg1	channels					956:963	the two most favorable channels	933:963	the two most favorable channels	933:963	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	6	5	theme	dynamics	1017:1024	arg1	simulations					1033:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	2	6	theme	many	335:338	arg1	reactions					383:391	many important cellular physiological catalytic reactions	335:391	many important cellular physiological catalytic reactions	335:391	It plays an important role in many important cellular physiological catalytic reactions.
30550897	1	7	from	protein	296:302	arg1	threonine					272:280	threonine	272:280	threonine	272:280	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	7	from	protein	296:302	arg1	group					251:255	the hydroxyl group	238:255	the hydroxyl group of a serine or threonine in the target protein	238:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	7	from	protein	296:302	arg1	serine					262:267	serine	262:267	serine	262:267	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	4	8	from	stabilization	720:732	arg1	site					748:751	the active site	737:751	the active site	737:751	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	4	8	from	stabilization	720:732	arg1	OGT					756:758	OGT	756:758	OGT	756:758	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	4	9	theme	UDP	716:718	arg1	stabilization					720:732	the UDP stabilization	712:732	the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur	712:816	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	1	10	theme	serine	262:267	arg1	threonine					272:280	threonine	272:280	threonine	272:280	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	10	theme	serine	262:267	arg1	group					251:255	the hydroxyl group	238:255	the hydroxyl group of a serine or threonine in the target protein	238:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	10	theme	serine	262:267	arg1	serine					262:267	serine	262:267	serine	262:267	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	3	11	theme	release	543:549	arg1	mechanism					551:559	the hydrogen-bond-dependent release mechanism	515:559	the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations	461:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	8	12	theme	main	1296:1299	arg1	13 kcal/mol					1324:1334	13 kcal/mol	1324:1334	13 kcal/mol	1324:1334	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	8	12	theme	main	1296:1299	arg1	barrier					1313:1319	the main free energy barrier	1292:1319	the main free energy barrier	1292:1319	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	5	13	from	calculations	823:834	arg1	forms					850:854	the mutant forms	839:854	the mutant forms	839:854	The calculations on the mutant forms support our results.
30550897	3	14	theme	uridine	478:484	arg1	diphosphate					486:496	uridine diphosphate	478:496	uridine diphosphate	478:496	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	3	14	theme	uridine	478:484	arg1	UDP					499:501	UDP	499:501	UDP	499:501	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	6	15	theme	velocity	1072:1079	arg1	method					1095:1100	the constant velocity pulling (PCV) method	1059:1100	the constant velocity pulling (PCV) method	1059:1100	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	4	16	theme	Asp925	656:661	arg1	residues					663:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	6	17	theme	PCV	1090:1092	arg1	method					1095:1100	the constant velocity pulling (PCV) method	1059:1100	the constant velocity pulling (PCV) method	1059:1100	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	4	18	theme	major	698:702	arg1	role					704:707	a major role	696:707	a major role	696:707	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	3	19	dep	product	469:475	arg1	diphosphate					486:496	uridine diphosphate	478:496	uridine diphosphate	478:496	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	3	19	dep	product	469:475	arg1	UDP					499:501	UDP	499:501	UDP	499:501	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	4	20	theme	His901	644:649	arg1	residues					663:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	4	21	theme	Lys842	636:641	arg1	residues					663:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	5	22	theme	mutant	843:848	arg1	forms					850:854	the mutant forms	839:854	the mutant forms	839:854	The calculations on the mutant forms support our results.
30550897	10	23	theme	ligand	1572:1577	arg1	mechanism					1589:1597	the ligand transport mechanism	1568:1597	the ligand transport mechanism in the OGT enzymatic process	1568:1626	This work clarifies the ligand transport mechanism in the OGT enzymatic process and is a great resource for designing inhibitors based on UDP or UDP-GlcNAc.
30550897	8	24	theme	energy	1306:1311	arg1	13 kcal/mol					1324:1334	13 kcal/mol	1324:1334	13 kcal/mol	1324:1334	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	8	24	theme	energy	1306:1311	arg1	barrier					1313:1319	the main free energy barrier	1292:1319	the main free energy barrier	1292:1319	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	1	25	theme	covalent	186:193	arg1	bonding					195:201	the covalent bonding	182:201	the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein	182:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	7	26	theme	dynamic	1125:1131	arg1	properties					1133:1142	The thermodynamic and dynamic properties	1103:1142	The thermodynamic and dynamic properties as along with the corresponding mechanism	1103:1184	The thermodynamic and dynamic properties as along with the corresponding mechanism were determined and discussed according to the umbrella sampling technique.
30550897	1	27	from	threonine	272:280	arg1	protein					296:302	the target protein	285:302	the target protein	285:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	28	theme	O-linked	97:104	arg1	enzyme					160:165	an essential enzyme	147:165	an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein	147:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	28	theme	O-linked	97:104	arg1	OGT					139:141	OGT	139:141	OGT	139:141	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	28	theme	O-linked	97:104	arg1	transferase					126:136	O-linked N-acetylglucosamine transferase	97:136	O-linked N-acetylglucosamine transferase (OGT)	97:142	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	7	29	theme	umbrella	1233:1240	arg1	technique					1251:1259	the umbrella sampling technique	1229:1259	the umbrella sampling technique	1229:1259	The thermodynamic and dynamic properties as along with the corresponding mechanism were determined and discussed according to the umbrella sampling technique.
30550897	3	30	theme	binding	417:423	arg1	mode					425:428	the binding mode	413:428	the binding mode	413:428	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	0	31	theme	Uridine	0:6	arg1	diphosphate					8:18	Uridine diphosphate	0:18	Uridine diphosphate	0:18	Uridine diphosphate release mechanism in O-N-acetylglucosamine (O-GlcNAc) transferase catalysis.
30550897	1	32	theme	threonine	272:280	arg1	threonine					272:280	threonine	272:280	threonine	272:280	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	32	theme	threonine	272:280	arg1	group					251:255	the hydroxyl group	238:255	the hydroxyl group of a serine or threonine in the target protein	238:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	32	theme	threonine	272:280	arg1	serine					262:267	serine	262:267	serine	262:267	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	4	33	theme	π-π	788:790	arg1	interactions					792:803	π-π interactions	788:803	π-π interactions	788:803	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	1	34	theme	N-acetylglucosamine	106:124	arg1	enzyme					160:165	an essential enzyme	147:165	an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein	147:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	34	theme	N-acetylglucosamine	106:124	arg1	OGT					139:141	OGT	139:141	OGT	139:141	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	34	theme	N-acetylglucosamine	106:124	arg1	transferase					126:136	O-linked N-acetylglucosamine transferase	97:136	O-linked N-acetylglucosamine transferase (OGT)	97:142	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	2	35	theme	catalytic	373:381	arg1	reactions					383:391	many important cellular physiological catalytic reactions	335:391	many important cellular physiological catalytic reactions	335:391	It plays an important role in many important cellular physiological catalytic reactions.
30550897	7	36	theme	thermodynamic	1107:1119	arg1	properties					1133:1142	The thermodynamic and dynamic properties	1103:1142	The thermodynamic and dynamic properties as along with the corresponding mechanism	1103:1184	The thermodynamic and dynamic properties as along with the corresponding mechanism were determined and discussed according to the umbrella sampling technique.
30550897	1	37	from	serine	262:267	arg1	protein					296:302	the target protein	285:302	the target protein	285:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	9	38	theme	other	1521:1525	arg1	obstacles					1537:1545	the other two small obstacles	1517:1545	the other two small obstacles	1517:1545	Moreover, the unstable hydrogen bonds and the rollback of the ligand likely cause the other two small obstacles.
30550897	9	39	theme	small	1531:1535	arg1	obstacles					1537:1545	the other two small obstacles	1517:1545	the other two small obstacles	1517:1545	Moreover, the unstable hydrogen bonds and the rollback of the ligand likely cause the other two small obstacles.
30550897	1	40	theme	N-acetylglucosamine	206:224	arg1	bonding					195:201	the covalent bonding	182:201	the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein	182:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	3	41	theme	mechanism	551:559	arg1	energy					451:456	the binding free energy	434:456	the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations	434:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	3	41	theme	mechanism	551:559	arg1	mode					425:428	the binding mode	413:428	the binding mode	413:428	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	9	42	theme	ligand	1497:1502	arg1	bonds					1467:1471	the unstable hydrogen bonds	1445:1471	the unstable hydrogen bonds	1445:1471	Moreover, the unstable hydrogen bonds and the rollback of the ligand likely cause the other two small obstacles.
30550897	9	42	theme	ligand	1497:1502	arg1	rollback					1481:1488	the rollback	1477:1488	the rollback of the ligand	1477:1502	Moreover, the unstable hydrogen bonds and the rollback of the ligand likely cause the other two small obstacles.
30550897	9	43	theme	unstable	1449:1456	arg1	bonds					1467:1471	the unstable hydrogen bonds	1445:1471	the unstable hydrogen bonds	1445:1471	Moreover, the unstable hydrogen bonds and the rollback of the ligand likely cause the other two small obstacles.
30550897	3	44	theme	hydrogen-bond-dependent	519:541	arg1	mechanism					551:559	the hydrogen-bond-dependent release mechanism	515:559	the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations	461:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	1	45	theme	essential	150:158	arg1	enzyme					160:165	an essential enzyme	147:165	an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein	147:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	45	theme	essential	150:158	arg1	transferase					126:136	O-linked N-acetylglucosamine transferase	97:136	O-linked N-acetylglucosamine transferase (OGT)	97:142	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	0	46	theme	O-N-acetylglucosamine	41:61	arg1	transferase					74:84	O-N-acetylglucosamine (O-GlcNAc) transferase	41:84	O-N-acetylglucosamine (O-GlcNAc) transferase catalysis	41:94	Uridine diphosphate release mechanism in O-N-acetylglucosamine (O-GlcNAc) transferase catalysis.
30550897	1	47	theme	target	289:294	arg1	protein					296:302	the target protein	285:302	the target protein	285:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	6	48	theme	acceleration	994:1005	arg1	simulations					1033:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	3	49	theme	molecular	577:585	arg1	simulations					595:605	extensive molecular dynamic simulations	567:605	extensive molecular dynamic simulations	567:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	10	50	theme	transport	1579:1587	arg1	mechanism					1589:1597	the ligand transport mechanism	1568:1597	the ligand transport mechanism in the OGT enzymatic process	1568:1626	This work clarifies the ligand transport mechanism in the OGT enzymatic process and is a great resource for designing inhibitors based on UDP or UDP-GlcNAc.
30550897	3	51	theme	binding	438:444	arg1	energy					451:456	the binding free energy	434:456	the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations	434:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	6	52	theme	RAMD	1027:1030	arg1	simulations					1033:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	6	53	theme	release	894:900	arg1	channels					902:909	Sixteen possible release channels	877:909	Sixteen possible release channels	877:909	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	8	54	theme	optimal	1275:1281	arg1	channel					1283:1289	the most optimal channel	1266:1289	the most optimal channel	1266:1289	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	3	55	theme	dynamic	587:593	arg1	simulations					595:605	extensive molecular dynamic simulations	567:605	extensive molecular dynamic simulations	567:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	10	56	from	mechanism	1589:1597	arg1	process					1620:1626	the OGT enzymatic process	1602:1626	the OGT enzymatic process	1602:1626	This work clarifies the ligand transport mechanism in the OGT enzymatic process and is a great resource for designing inhibitors based on UDP or UDP-GlcNAc.
30550897	3	57	theme	free	446:449	arg1	energy					451:456	the binding free energy	434:456	the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations	434:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	0	58	theme	O-GlcNAc	64:71	arg1	transferase					74:84	O-N-acetylglucosamine (O-GlcNAc) transferase	41:84	O-N-acetylglucosamine (O-GlcNAc) transferase catalysis	41:94	Uridine diphosphate release mechanism in O-N-acetylglucosamine (O-GlcNAc) transferase catalysis.
30550897	6	59	theme	possible	885:892	arg1	channels					902:909	Sixteen possible release channels	877:909	Sixteen possible release channels	877:909	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	8	60	theme	free	1301:1304	arg1	13 kcal/mol					1324:1334	13 kcal/mol	1324:1334	13 kcal/mol	1324:1334	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	8	60	theme	free	1301:1304	arg1	barrier					1313:1319	the main free energy barrier	1292:1319	the main free energy barrier	1292:1319	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	8	61	theme	Ala896	1407:1412	arg1	residues					1425:1432	the Ala896 and Asp925 residues	1403:1432	residues	1425:1432	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	4	62	theme	hydrogen	767:774	arg1	bonding					776:782	hydrogen bonding	767:782	hydrogen bonding	767:782	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	6	63	theme	constant	1063:1070	arg1	method					1095:1100	the constant velocity pulling (PCV) method	1059:1100	the constant velocity pulling (PCV) method	1059:1100	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	3	64	theme	product	469:475	arg1	energy					451:456	the binding free energy	434:456	the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations	434:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	3	64	theme	product	469:475	arg1	mode					425:428	the binding mode	413:428	the binding mode	413:428	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	9	65	theme	hydrogen	1458:1465	arg1	bonds					1467:1471	the unstable hydrogen bonds	1445:1471	the unstable hydrogen bonds	1445:1471	Moreover, the unstable hydrogen bonds and the rollback of the ligand likely cause the other two small obstacles.
30550897	1	66	from	group	251:255	arg1	protein					296:302	the target protein	285:302	the target protein	285:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	10	67	theme	enzymatic	1610:1618	arg1	process					1620:1626	the OGT enzymatic process	1602:1626	the OGT enzymatic process	1602:1626	This work clarifies the ligand transport mechanism in the OGT enzymatic process and is a great resource for designing inhibitors based on UDP or UDP-GlcNAc.
30550897	3	68	theme	extensive	567:575	arg1	simulations					595:605	extensive molecular dynamic simulations	567:605	extensive molecular dynamic simulations	567:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	7	69	theme	sampling	1242:1249	arg1	technique					1251:1259	the umbrella sampling technique	1229:1259	the umbrella sampling technique	1229:1259	The thermodynamic and dynamic properties as along with the corresponding mechanism were determined and discussed according to the umbrella sampling technique.
30550897	10	70	theme	great	1637:1641	arg1	resource					1643:1650	a great resource	1635:1650	a great resource for designing inhibitors based on UDP or UDP-GlcNAc	1635:1702	This work clarifies the ligand transport mechanism in the OGT enzymatic process and is a great resource for designing inhibitors based on UDP or UDP-GlcNAc.
30550897	8	71	theme	Asp925	1418:1423	arg1	residues					1425:1432	the Ala896 and Asp925 residues	1403:1432	residues	1425:1432	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	4	72	theme	active	741:746	arg1	site					748:751	the active site	737:751	the active site	737:751	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	4	72	theme	active	741:746	arg1	OGT					756:758	OGT	756:758	OGT	756:758	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	4	73	theme	OGT	756:758	arg1	site					748:751	the active site	737:751	the active site	737:751	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	4	73	theme	OGT	756:758	arg1	OGT					756:758	OGT	756:758	OGT	756:758	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	2	74	theme	important	317:325	arg1	role					327:330	an important role	314:330	an important role	314:330	It plays an important role in many important cellular physiological catalytic reactions.
30550897	8	75	theme	hydrogen	1372:1379	arg1	bonds					1381:1385	the hydrogen bonds	1368:1385	the hydrogen bonds between UDP and the Ala896 and Asp925 residues	1368:1432	For the most optimal channel, the main free energy barrier is 13 kcal/mol, which probably originates from the hydrogen bonds between UDP and the Ala896 and Asp925 residues.
30550897	10	76	theme	OGT	1606:1608	arg1	process					1620:1626	the OGT enzymatic process	1602:1626	the OGT enzymatic process	1602:1626	This work clarifies the ligand transport mechanism in the OGT enzymatic process and is a great resource for designing inhibitors based on UDP or UDP-GlcNAc.
30550897	3	77	theme	OGT	465:467	arg1	product					469:475	the OGT product	461:475	the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations	461:605	Here, we determine the binding mode and the binding free energy of the OGT product (uridine diphosphate, UDP) as well as the hydrogen-bond-dependent release mechanism using extensive molecular dynamic simulations.
30550897	6	78	theme	pulling	1081:1087	arg1	method					1095:1100	the constant velocity pulling (PCV) method	1059:1100	the constant velocity pulling (PCV) method	1059:1100	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	0	79	theme	transferase	74:84	arg1	catalysis					86:94	O-N-acetylglucosamine (O-GlcNAc) transferase catalysis	41:94	O-N-acetylglucosamine (O-GlcNAc) transferase catalysis	41:94	Uridine diphosphate release mechanism in O-N-acetylglucosamine (O-GlcNAc) transferase catalysis.
30550897	6	80	theme	random	987:992	arg1	simulations					1033:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	random acceleration molecular dynamics (RAMD) simulations	987:1043	Sixteen possible release channels were identified while the two most favorable channels were determined using random acceleration molecular dynamics (RAMD) simulations combined with the constant velocity pulling (PCV) method.
30550897	4	81	theme	Asn838	620:625	arg1	residues					663:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues	608:670	The Lys634, Asn838, Gln839, Lys842, His901, and Asp925 residues were identified to play a major role in the UDP stabilization in the active site of OGT, where hydrogen bonding and π-π interactions mainly occur.
30550897	2	82	theme	physiological	359:371	arg1	reactions					383:391	many important cellular physiological catalytic reactions	335:391	many important cellular physiological catalytic reactions	335:391	It plays an important role in many important cellular physiological catalytic reactions.
30550897	1	83	theme	hydroxyl	242:249	arg1	threonine					272:280	threonine	272:280	threonine	272:280	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	83	theme	hydroxyl	242:249	arg1	group					251:255	the hydroxyl group	238:255	the hydroxyl group of a serine or threonine in the target protein	238:302	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	1	83	theme	hydroxyl	242:249	arg1	serine					262:267	serine	262:267	serine	262:267	O-linked N-acetylglucosamine transferase (OGT) is an essential enzyme that catalyzes the covalent bonding of N-acetylglucosamine (GlcNAc) to the hydroxyl group of a serine or threonine in the target protein.
30550897	2	84	theme	cellular	350:357	arg1	reactions					383:391	many important cellular physiological catalytic reactions	335:391	many important cellular physiological catalytic reactions	335:391	It plays an important role in many important cellular physiological catalytic reactions.
29739316	3	0	theme	numerous	317:324	arg1	deficiencies					337:348	numerous expression deficiencies	317:348	numerous expression deficiencies	317:348	While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects.
29739316	0	1	from	survey	14:19	arg1	line					53:56	the Jurkat cell line	37:56	the Jurkat cell line	37:56	A genome-wide survey of mutations in the Jurkat cell line.
29739316	2	2	theme	human	296:300	arg1	cells					304:308	normal human T cells	289:308	normal human T cells	289:308	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	7	3	dep	CONCLUSIONS	880:890	arg1	harbors					913:919	harbors	913:919	harbors many mutations that are associated with cancer and contribute to Jurkat's unique characteristics	913:1016	CONCLUSIONS The Jurkat cell line harbors many mutations that are associated with cancer and contribute to Jurkat's unique characteristics.
29739316	4	4	theme	variation	511:519	arg1	catolog					492:498	a comprehensive catolog	476:498	a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing	476:576	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	6	5	theme	cell	869:872	arg1	line					874:877	the cell line	865:877	the cell line	865:877	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	2	6	theme	normal	289:294	arg1	cells					304:308	normal human T cells	289:308	normal human T cells	289:308	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	4	7	theme	genomic	503:509	arg1	variation					511:519	genomic variation	503:519	genomic variation	503:519	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	1	8	contain	has	91:93	arg2	model					121:125	a model	119:125	a model of T cell signaling	119:145	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	1	8	contain	has	91:93	arg2	history					108:114	an extensive history	95:114	an extensive history	95:114	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	1	8	contain	has	91:93	arg1	line					86:89	The Jurkat cell line	70:89	The Jurkat cell line	70:89	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	7	9	theme	cell	903:906	arg1	line					908:911	The Jurkat cell line	892:911	The Jurkat cell line	892:911	CONCLUSIONS The Jurkat cell line harbors many mutations that are associated with cancer and contribute to Jurkat's unique characteristics.
29739316	9	10	theme	studies	1418:1424	arg1	interpretation					1354:1367	the interpretation	1350:1367	the interpretation of past research	1350:1384	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	9	10	theme	studies	1418:1424	arg1	design					1394:1399	the design	1390:1399	the design of future Jurkat studies	1390:1424	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	8	11	dep	maintenance	1147:1157	arg1	MSH2					1195:1198	MSH2	1195:1198	MSH2	1195:1198	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	11	dep	maintenance	1147:1157	arg1	TP53					1180:1183	TP53	1180:1183	TP53	1180:1183	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	11	dep	maintenance	1147:1157	arg1	BAX					1186:1188	BAX	1186:1188	BAX	1186:1188	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	5	12	theme	damaging	664:671	arg1	mutations					673:681	damaging mutations	664:681	damaging mutations	664:681	With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects.
29739316	8	13	dep	signaling	1105:1113	arg1	CTLA4					1130:1134	CTLA4	1130:1134	CTLA4	1130:1134	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	13	dep	signaling	1105:1113	arg1	SYK					1141:1143	SYK	1141:1143	SYK	1141:1143	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	13	dep	signaling	1105:1113	arg1	INPP5D					1122:1127	INPP5D	1122:1127	INPP5D	1122:1127	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	13	dep	signaling	1105:1113	arg1	PTEN					1116:1119	PTEN	1116:1119	PTEN	1116:1119	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	6	14	theme	documented	745:754	arg1	mutations					756:764	documented mutations	745:764	documented mutations in Jurkat	745:774	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	9	15	theme	future	1404:1409	arg1	studies					1418:1424	future Jurkat studies	1404:1424	future Jurkat studies	1404:1424	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	6	16	from	abnormalities	848:860	arg1	line					874:877	the cell line	865:877	the cell line	865:877	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	6	17	theme	expression	837:846	arg1	abnormalities					848:860	observed expression abnormalities	828:860	observed expression abnormalities in the cell line	828:877	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	8	18	theme	stability	1169:1177	arg1	maintenance					1147:1157	maintenance	1147:1157	maintenance of genome stability (TP53, BAX, and MSH2)	1147:1199	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	18	theme	stability	1169:1177	arg1	C1GALT1C1					1230:1238	C1GALT1C1	1230:1238	C1GALT1C1	1230:1238	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	18	theme	stability	1169:1177	arg1	signaling					1105:1113	T-cell receptor signaling	1089:1113	T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK)	1089:1144	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	18	theme	stability	1169:1177	arg1	glycosylation					1215:1227	O-linked glycosylation	1206:1227	O-linked glycosylation (C1GALT1C1)	1206:1239	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	1	19	theme	T	130:130	arg1	signaling					137:145	T cell signaling	130:145	T cell signaling	130:145	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	5	20	dep	detectable	601:610	arg1	non-reference					613:625	non-reference	613:625	non-reference	613:625	With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects.
29739316	6	21	theme	observed	828:835	arg1	abnormalities					848:860	observed expression abnormalities	828:860	observed expression abnormalities in the cell line	828:877	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	4	22	theme	Jurkat	528:533	arg1	line					540:543	the Jurkat cell line	524:543	the Jurkat cell line based on whole-genome sequencing	524:576	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	1	23	theme	cell	132:135	arg1	signaling					137:145	T cell signaling	130:145	T cell signaling	130:145	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	0	24	theme	genome-wide	2:12	arg1	survey					14:19	A genome-wide survey	0:19	A genome-wide survey of mutations in the Jurkat cell line.	0:57	A genome-wide survey of mutations in the Jurkat cell line.
29739316	8	25	gly	glycosylation	1215:1227	arg1	stability					1169:1177	genome stability	1162:1177	genome stability	1162:1177	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	7	26	theme	Jurkat	896:901	arg1	line					908:911	The Jurkat cell line	892:911	The Jurkat cell line	892:911	CONCLUSIONS The Jurkat cell line harbors many mutations that are associated with cancer and contribute to Jurkat's unique characteristics.
29739316	7	27	theme	unique	995:1000	arg1	characteristics					1002:1016	Jurkat's unique characteristics	986:1016	Jurkat's unique characteristics	986:1016	CONCLUSIONS The Jurkat cell line harbors many mutations that are associated with cancer and contribute to Jurkat's unique characteristics.
29739316	1	28	theme	signaling	137:145	arg1	history					108:114	an extensive history	95:114	an extensive history	95:114	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	1	28	theme	signaling	137:145	arg1	model					121:125	a model	119:125	a model of T cell signaling	119:145	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	3	29	theme	expression	326:335	arg1	deficiencies					337:348	numerous expression deficiencies	317:348	numerous expression deficiencies	317:348	While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects.
29739316	4	30	theme	comprehensive	478:490	arg1	catolog					492:498	a comprehensive catolog	476:498	a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing	476:576	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	1	31	theme	Jurkat	74:79	arg1	line					86:89	The Jurkat cell line	70:89	The Jurkat cell line	70:89	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	8	32	theme	receptor	1096:1103	arg1	signaling					1105:1113	T-cell receptor signaling	1089:1113	T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK)	1089:1144	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	6	33	from	mutations	756:764	arg1	Jurkat					769:774	Jurkat	769:774	Jurkat	769:774	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	6	34	from	variants	816:823	arg1	links					788:792	links	788:792	links from detrimental gene variants to observed expression abnormalities in the cell line	788:877	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	4	35	from	catolog	492:498	arg1	line					540:543	the Jurkat cell line	524:543	the Jurkat cell line based on whole-genome sequencing	524:576	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	5	36	theme	sequences	627:635	arg1	list					589:592	this list	584:592	this list of all detectable, non-reference sequences	584:635	With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects.
29739316	1	37	theme	cell	81:84	arg1	line					86:89	The Jurkat cell line	70:89	The Jurkat cell line	70:89	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	8	38	with	Genes	1019:1023	arg1	mutations					1039:1047	damaging mutations	1030:1047	damaging mutations in the Jurkat cell line	1030:1071	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	4	39	theme	whole-genome	554:565	arg1	sequencing					567:576	whole-genome sequencing	554:576	whole-genome sequencing	554:576	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	8	40	theme	damaging	1030:1037	arg1	mutations					1039:1047	damaging mutations	1030:1047	damaging mutations in the Jurkat cell line	1030:1071	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	3	41	theme	defects	443:449	arg1	handful					432:438	a handful	430:438	a handful of defects	430:449	While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects.
29739316	8	42	theme	T-cell	1089:1094	arg1	signaling					1105:1113	T-cell receptor signaling	1089:1113	T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK)	1089:1144	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	5	43	theme	functional	714:723	arg1	effects					725:731	functional effects	714:731	functional effects	714:731	With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects.
29739316	8	44	theme	O-linked	1206:1213	arg1	C1GALT1C1					1230:1238	C1GALT1C1	1230:1238	C1GALT1C1	1230:1238	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	44	theme	O-linked	1206:1213	arg1	glycosylation					1215:1227	O-linked glycosylation	1206:1227	O-linked glycosylation (C1GALT1C1)	1206:1239	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	6	45	theme	gene	811:814	arg1	variants					816:823	detrimental gene variants	799:823	detrimental gene variants	799:823	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	2	46	theme	century	176:182	arg1	turn					159:162	the turn	155:162	the turn of the 21st century	155:182	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	8	47	theme	genome	1162:1167	arg1	stability					1169:1177	genome stability	1162:1177	genome stability	1162:1177	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	0	48	theme	mutations	24:32	arg1	survey					14:19	A genome-wide survey	0:19	A genome-wide survey of mutations in the Jurkat cell line.	0:57	A genome-wide survey of mutations in the Jurkat cell line.
29739316	4	49	dep	RESULTS	452:458	arg1	report					469:474	report	469:474	report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing	469:576	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	6	50	theme	detrimental	799:809	arg1	variants					816:823	detrimental gene variants	799:823	detrimental gene variants	799:823	We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.
29739316	2	51	theme	21st	171:174	arg1	century					176:182	the 21st century	167:182	the 21st century	167:182	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	0	52	theme	Jurkat	41:46	arg1	line					53:56	the Jurkat cell line	37:56	the Jurkat cell line	37:56	A genome-wide survey of mutations in the Jurkat cell line.
29739316	8	53	theme	cell	1063:1066	arg1	line					1068:1071	the Jurkat cell line	1052:1071	the Jurkat cell line	1052:1071	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	5	54	theme	public	693:698	arg1	databases					700:708	public databases	693:708	public databases for functional effects	693:731	With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects.
29739316	8	55	theme	Jurkat	1056:1061	arg1	line					1068:1071	the Jurkat cell line	1052:1071	the Jurkat cell line	1052:1071	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	9	56	theme	past	1372:1375	arg1	research					1377:1384	past research	1372:1384	past research	1372:1384	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	9	57	theme	Jurkat	1411:1416	arg1	studies					1418:1424	future Jurkat studies	1404:1424	future Jurkat studies	1404:1424	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	5	58	theme	detectable	601:610	arg1	sequences					627:635	all detectable, non-reference sequences	597:635	all detectable, non-reference sequences	597:635	With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects.
29739316	1	59	dep	BACKGROUND	59:68	arg1	has					91:93	has	91:93	has an extensive history as a model of T cell signaling	91:145	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	2	60	located	observed	221:228	arg2	irregularities					201:214	some expression irregularities	185:214	some expression irregularities	185:214	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	2	60	located	observed	221:228	arg1	turn					159:162	the turn	155:162	the turn of the 21st century	155:182	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	7	61	theme	many	921:924	arg1	mutations					926:934	many mutations	921:934	many mutations that are associated with cancer and contribute to Jurkat's unique characteristics	921:1016	CONCLUSIONS The Jurkat cell line harbors many mutations that are associated with cancer and contribute to Jurkat's unique characteristics.
29739316	1	62	theme	extensive	98:106	arg1	history					108:114	an extensive history	95:114	an extensive history	95:114	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	1	62	theme	extensive	98:106	arg1	model					121:125	a model	119:125	a model of T cell signaling	119:145	BACKGROUND The Jurkat cell line has an extensive history as a model of T cell signaling.
29739316	4	63	theme	cell	535:538	arg1	line					540:543	the Jurkat cell line	524:543	the Jurkat cell line based on whole-genome sequencing	524:576	RESULTS Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing.
29739316	8	64	link	O-linked	1206:1213	arg1	C1GALT1C1					1230:1238	C1GALT1C1	1230:1238	C1GALT1C1	1230:1238	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	8	64	link	O-linked	1206:1213	arg1	glycosylation					1215:1227	O-linked glycosylation	1206:1227	O-linked glycosylation (C1GALT1C1)	1206:1239	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	2	65	theme	expression	190:199	arg1	irregularities					201:214	some expression irregularities	185:214	some expression irregularities	185:214	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	9	66	theme	molecular	1277:1285	arg1	experiments					1287:1297	molecular experiments	1277:1297	molecular experiments	1277:1297	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	2	67	theme	cell	268:271	arg1	line					273:276	the cell line	264:276	the cell line	264:276	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	9	68	theme	research	1377:1384	arg1	interpretation					1354:1367	the interpretation	1350:1367	the interpretation of past research	1350:1384	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	9	68	theme	research	1377:1384	arg1	design					1394:1399	the design	1390:1399	the design of future Jurkat studies	1390:1424	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
29739316	3	69	theme	genetic	381:387	arg1	explanations					389:400	genetic explanations	381:400	genetic explanations	381:400	While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects.
29739316	8	70	from	mutations	1039:1047	arg1	line					1068:1071	the Jurkat cell line	1052:1071	the Jurkat cell line	1052:1071	Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1).
29739316	0	71	theme	cell	48:51	arg1	line					53:56	the Jurkat cell line	37:56	the Jurkat cell line	37:56	A genome-wide survey of mutations in the Jurkat cell line.
29739316	2	72	theme	T	302:302	arg1	cells					304:308	normal human T cells	289:308	normal human T cells	289:308	But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells.
29739316	9	73	theme	experiments	1287:1297	arg1	decades					1266:1272	decades	1266:1272	decades of molecular experiments	1266:1297	This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.
31456688	8	0	theme	Further	1846:1852	arg1	simulations					1883:1893	Further parametric exploration-based simulations	1846:1893	Further parametric exploration-based simulations	1846:1893	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	8	1	theme	exploration-based	1865:1881	arg1	simulations					1883:1893	Further parametric exploration-based simulations	1846:1893	Further parametric exploration-based simulations	1846:1893	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	7	2	theme	trained	1568:1574	arg1	model					1590:1594	The trained computational model	1564:1594	The trained computational model	1564:1594	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	4	3	theme	time-lapse	907:916	arg1	observations					930:941	End point and time-lapse microscopic observations	893:941	observations	930:941	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	6	4	theme	experimental	1491:1502	arg1	model					1504:1508	the experimental model	1487:1508	the experimental model	1487:1508	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	8	5	theme	breast	2080:2085	arg1	cells					2094:2098	breast cancer cells	2080:2098	breast cancer cells	2080:2098	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	3	6	dep	three-dimensional	641:657	arg1	3D					660:661	3D	660:661	3D	660:661	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	8	7	theme	cells	2094:2098	arg1	invasion					2068:2075	multiscale invasion	2057:2075	multiscale invasion of breast cancer cells	2057:2098	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	8	8	theme	specific	1908:1915	arg1	regimes					1928:1934	specific permissive regimes	1908:1934	specific permissive regimes	1908:1934	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	2	9	theme	models	599:604	arg1	construction					531:542	the construction	527:542	the construction of increasingly complex experimental and computational models	527:604	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	4	10	theme	cancer	997:1002	arg1	invasion					1004:1011	cancer invasion	997:1011	cancer invasion	997:1011	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	6	11	theme	cell	1330:1333	arg1	proliferation					1335:1347	cell proliferation	1330:1347	cell proliferation	1330:1347	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	5	12	theme	modeling	1157:1164	arg1	Compucell3D					1178:1188	the modeling environment Compucell3D	1153:1188	the modeling environment Compucell3D that is based on the Glazier-Graner-Hogeweg model	1153:1238	We then simulate our experimental observations using the modeling environment Compucell3D that is based on the Glazier-Graner-Hogeweg model.
31456688	8	13	theme	cell-cell	1939:1947	arg1	adhesions					1965:1973	cell-cell and cell-matrix adhesions	1939:1973	cell-cell and cell-matrix adhesions	1939:1973	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	1	14	theme	surrounding	252:262	arg1	cells					299:303	surrounding untransformed but affected stromal cells	252:303	surrounding untransformed but affected stromal cells	252:303	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	3	15	theme	stromal	832:838	arg1	milieu					840:845	its surrounding stromal milieu	816:845	its surrounding stromal milieu	816:845	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	3	16	theme	three-dimensional	641:657	arg1	organo-					664:670	a multiscale three-dimensional (3D) organo-	628:670	a multiscale three-dimensional (3D) organo-	628:670	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	8	17	theme	cell-matrix	1953:1963	arg1	adhesions					1965:1973	cell-cell and cell-matrix adhesions	1939:1973	cell-cell and cell-matrix adhesions	1939:1973	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	7	18	theme	matrix	1753:1758	arg1	metalloproteinase					1760:1776	matrix metalloproteinase	1753:1776	matrix metalloproteinase activity	1753:1785	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	3	19	theme	solitary	865:872	arg1	dynamics					883:890	solitary motility dynamics	865:890	solitary motility dynamics	865:890	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	6	20	theme	reaction-diffusion-based	1394:1417	arg1	dynamics					1429:1436	reaction-diffusion-based morphogen dynamics	1394:1436	reaction-diffusion-based morphogen dynamics	1394:1436	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	7	21	dep	treatments	1700:1709	arg1	treatments					1700:1709	pharmacological treatments	1684:1709	pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity)	1684:1786	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	7	21	dep	treatments	1700:1709	arg1	activity					1778:1785	matrix metalloproteinase activity	1753:1785	matrix metalloproteinase activity	1753:1785	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	7	21	dep	treatments	1700:1709	arg1	inhibition					1712:1721	inhibition	1712:1721	inhibition of N-linked glycosylation	1712:1747	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	3	22	theme	pathotypic	676:685	arg1	assay					700:704	pathotypic experimental assay	676:704	pathotypic experimental assay	676:704	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	7	23	theme	glycosylation	1735:1747	arg1	treatments					1700:1709	pharmacological treatments	1684:1709	pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity)	1684:1786	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	7	23	theme	glycosylation	1735:1747	arg1	activity					1778:1785	matrix metalloproteinase activity	1753:1785	matrix metalloproteinase activity	1753:1785	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	7	23	theme	glycosylation	1735:1747	arg1	inhibition					1712:1721	inhibition	1712:1721	inhibition of N-linked glycosylation	1712:1747	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	4	24	theme	dynamical	1028:1036	arg1	interactions					1038:1049	the dynamical interactions	1024:1049	the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments	975:1097	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	6	25	theme	cancer	1299:1304	arg1	cells					1306:1310	cancer cells	1299:1310	cancer cells	1299:1310	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	0	26	theme	Multiscale	75:84	arg1	Invasion					86:93	Multiscale Invasion	75:93	Multiscale Invasion	75:93	An Interplay Between Reaction-Diffusion and Cell-Matrix Adhesion Regulates Multiscale Invasion in Early Breast Carcinomatosis.
31456688	8	27	theme	surrounding	2167:2177	arg1	stroma					2179:2184	their surrounding stroma	2161:2184	their surrounding stroma	2161:2184	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	5	28	theme	Glazier-Graner-Hogeweg	1211:1232	arg1	model					1234:1238	the Glazier-Graner-Hogeweg model	1207:1238	the Glazier-Graner-Hogeweg model	1207:1238	We then simulate our experimental observations using the modeling environment Compucell3D that is based on the Glazier-Graner-Hogeweg model.
31456688	5	29	theme	experimental	1121:1132	arg1	observations					1134:1145	our experimental observations	1117:1145	our experimental observations	1117:1145	We then simulate our experimental observations using the modeling environment Compucell3D that is based on the Glazier-Graner-Hogeweg model.
31456688	1	30	theme	multiple	176:183	arg1	interactions					196:207	multiple reciprocal interactions	176:207	multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process	176:376	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	0	31	theme	Breast	104:109	arg1	Carcinomatosis					111:124	Early Breast Carcinomatosis	98:124	Early Breast Carcinomatosis	98:124	An Interplay Between Reaction-Diffusion and Cell-Matrix Adhesion Regulates Multiscale Invasion in Early Breast Carcinomatosis.
31456688	7	32	theme	pharmacological	1684:1698	arg1	treatments					1700:1709	pharmacological treatments	1684:1709	pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity)	1684:1786	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	7	32	theme	pharmacological	1684:1698	arg1	activity					1778:1785	matrix metalloproteinase activity	1753:1785	matrix metalloproteinase activity	1753:1785	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	7	32	theme	pharmacological	1684:1698	arg1	inhibition					1712:1721	inhibition	1712:1721	inhibition of N-linked glycosylation	1712:1747	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	2	33	theme	complex	560:566	arg1	models					599:604	increasingly complex experimental and computational models	547:604	increasingly complex experimental and computational models	547:604	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	8	34	theme	ECM	2035:2037	arg1	dynamics					2039:2046	a reaction-diffusion-regulated ECM dynamics	2004:2046	a reaction-diffusion-regulated ECM dynamics	2004:2046	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	7	35	theme	density	1836:1842	arg1	alteration					1813:1822	alteration	1813:1822	alteration of collagen density	1813:1842	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	2	36	theme	relative	415:422	arg1	contribution					424:435	the relative contribution	411:435	the relative contribution of such interactions to phenotypes associated with cancer cells	411:499	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	1	37	theme	extracellular	314:326	arg1	ECM					336:338	ECM	336:338	ECM	336:338	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	1	37	theme	extracellular	314:326	arg1	matrix					328:333	the extracellular matrix	310:333	the extracellular matrix (ECM)	310:339	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	1	38	from	progression	131:141	arg1	breast					160:165	the breast	156:165	the breast	156:165	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	6	39	theme	other	1530:1534	arg1	matrices					1536:1543	the other matrices	1526:1543	the other matrices	1526:1543	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	4	40	theme	epithelial	1063:1072	arg1	compartments					1086:1097	the epithelial and stromal compartments	1059:1097	the epithelial and stromal compartments	1059:1097	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	2	41	theme	interactions	445:456	arg1	contribution					424:435	the relative contribution	411:435	the relative contribution of such interactions to phenotypes associated with cancer cells	411:499	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	7	42	theme	counterparts	1649:1660	arg1	phenotypes					1618:1627	phenotypes	1618:1627	phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density)	1618:1843	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	4	43	theme	stromal	1078:1084	arg1	compartments					1086:1097	the epithelial and stromal compartments	1059:1097	the epithelial and stromal compartments	1059:1097	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	3	44	theme	unprecedented	731:743	arg1	extent					745:750	an unprecedented extent	728:750	an unprecedented extent	728:750	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	1	45	theme	untransformed	264:276	arg1	cells					299:303	surrounding untransformed but affected stromal cells	252:303	surrounding untransformed but affected stromal cells	252:303	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	1	46	theme	affected	282:289	arg1	cells					299:303	surrounding untransformed but affected stromal cells	252:303	surrounding untransformed but affected stromal cells	252:303	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	3	47	theme	histopathological	757:773	arg1	complexity					775:784	the histopathological complexity	753:784	the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics	753:890	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	8	48	theme	multiscale	2057:2066	arg1	invasion					2068:2075	multiscale invasion	2057:2075	multiscale invasion of breast cancer cells	2057:2098	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	2	49	theme	quantitative	381:392	arg1	understanding					394:406	A quantitative understanding	379:406	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells	379:499	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	7	50	theme	computational	1576:1588	arg1	model					1590:1594	The trained computational model	1564:1594	The trained computational model	1564:1594	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	6	51	theme	matrix	1368:1373	arg1	remodeling					1375:1384	matrix remodeling	1368:1384	matrix remodeling	1368:1384	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	4	52	theme	assay	951:955	arg1	observations					930:941	End point and time-lapse microscopic observations	893:941	observations	930:941	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	4	52	theme	assay	951:955	arg1	point					897:901	End point and time-lapse microscopic observations	893:941	point	897:901	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	3	53	theme	tumor	791:795	arg1	complexity					775:784	the histopathological complexity	753:784	the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics	753:890	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	8	54	theme	cancer	2087:2092	arg1	cells					2094:2098	breast cancer cells	2080:2098	breast cancer cells	2080:2098	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	8	55	theme	parametric	1854:1863	arg1	simulations					1883:1893	Further parametric exploration-based simulations	1846:1893	Further parametric exploration-based simulations	1846:1893	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	1	56	theme	reciprocal	185:194	arg1	interactions					196:207	multiple reciprocal interactions	176:207	multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process	176:376	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	7	57	theme	scaffold	1792:1799	arg1	modulation					1801:1810	scaffold modulation	1792:1810	scaffold modulation (alteration of collagen density)	1792:1843	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	4	58	theme	microscopic	918:928	arg1	observations					930:941	End point and time-lapse microscopic observations	893:941	observations	930:941	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	6	59	theme	computational	1245:1257	arg1	model					1259:1263	The computational model	1241:1263	The computational model	1241:1263	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	3	60	theme	surrounding	820:830	arg1	milieu					840:845	its surrounding stromal milieu	816:845	its surrounding stromal milieu	816:845	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	1	61	theme	transformed	229:239	arg1	epithelia					241:249	malignantly transformed epithelia	217:249	malignantly transformed epithelia	217:249	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	4	62	theme	earliest	979:986	arg1	steps					988:992	the earliest steps	975:992	the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments	975:1097	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	8	63	theme	permissive	1917:1926	arg1	regimes					1928:1934	specific permissive regimes	1908:1934	specific permissive regimes	1908:1934	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	7	64	theme	metalloproteinase	1760:1776	arg1	treatments					1700:1709	pharmacological treatments	1684:1709	pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity)	1684:1786	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	7	64	theme	metalloproteinase	1760:1776	arg1	activity					1778:1785	matrix metalloproteinase activity	1753:1785	matrix metalloproteinase activity	1753:1785	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	2	65	theme	computational	585:597	arg1	models					599:604	increasingly complex experimental and computational models	547:604	increasingly complex experimental and computational models	547:604	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	5	66	theme	environment	1166:1176	arg1	Compucell3D					1178:1188	the modeling environment Compucell3D	1153:1188	the modeling environment Compucell3D that is based on the Glazier-Graner-Hogeweg model	1153:1238	We then simulate our experimental observations using the modeling environment Compucell3D that is based on the Glazier-Graner-Hogeweg model.
31456688	3	67	theme	multiscale	630:639	arg1	organo-					664:670	a multiscale three-dimensional (3D) organo-	628:670	a multiscale three-dimensional (3D) organo-	628:670	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	6	68	theme	morphogen	1419:1427	arg1	dynamics					1429:1436	reaction-diffusion-based morphogen dynamics	1394:1436	reaction-diffusion-based morphogen dynamics	1394:1436	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	1	69	theme	cancer	146:151	arg1	progression					131:141	The progression	127:141	The progression of cancer in the breast	127:165	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31456688	7	70	theme	N-linked	1726:1733	arg1	glycosylation					1735:1747	N-linked glycosylation	1726:1747	N-linked glycosylation	1726:1747	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	3	71	theme	motility	874:881	arg1	dynamics					883:890	solitary motility dynamics	865:890	solitary motility dynamics	865:890	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	8	72	theme	adhesions	1965:1973	arg1	regimes					1928:1934	specific permissive regimes	1908:1934	specific permissive regimes	1908:1934	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	4	73	theme	invasion	1004:1011	arg1	steps					988:992	the earliest steps	975:992	the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments	975:1097	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	4	73	theme	invasion	1004:1011	arg1	interactions					1038:1049	the dynamical interactions	1024:1049	the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments	975:1097	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	0	74	theme	Early	98:102	arg1	Carcinomatosis					111:124	Early Breast Carcinomatosis	98:124	Early Breast Carcinomatosis	98:124	An Interplay Between Reaction-Diffusion and Cell-Matrix Adhesion Regulates Multiscale Invasion in Early Breast Carcinomatosis.
31456688	7	75	dep	modulation	1801:1810	arg1	alteration					1813:1822	alteration	1813:1822	alteration of collagen density	1813:1842	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	2	76	theme	experimental	568:579	arg1	models					599:604	increasingly complex experimental and computational models	547:604	increasingly complex experimental and computational models	547:604	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	6	77	theme	controls	1469:1476	arg1	run					1478:1480	controls run	1469:1480	controls run	1469:1480	The computational model, which comprises adhesion between cancer cells and the matrices, cell proliferation and apoptosis, and matrix remodeling through reaction-diffusion-based morphogen dynamics, is first trained to phenocopy controls run with the experimental model, wherein one or the other matrices have been removed.
31456688	2	78	theme	contribution	424:435	arg1	understanding					394:406	A quantitative understanding	379:406	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells	379:499	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	8	79	theme	reaction-diffusion-regulated	2006:2033	arg1	dynamics					2039:2046	a reaction-diffusion-regulated ECM dynamics	2004:2046	a reaction-diffusion-regulated ECM dynamics	2004:2046	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	2	80	theme	cancer	488:493	arg1	cells					495:499	cancer cells	488:499	cancer cells	488:499	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	7	81	link	N-linked	1726:1733	arg1	glycosylation					1735:1747	N-linked glycosylation	1726:1747	N-linked glycosylation	1726:1747	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	8	82	theme	dynamics	2039:2046	arg1	context					1993:1999	the context	1989:1999	the context of a reaction-diffusion-regulated ECM dynamics	1989:2046	Further parametric exploration-based simulations suggest that specific permissive regimes of cell-cell and cell-matrix adhesions, operating in the context of a reaction-diffusion-regulated ECM dynamics, promote multiscale invasion of breast cancer cells and determine the extent to which the latter migrate through their surrounding stroma.
31456688	7	83	theme	collagen	1827:1834	arg1	density					1836:1842	collagen density	1827:1842	collagen density	1827:1842	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	0	84	theme	Cell-Matrix	44:54	arg1	Adhesion					56:63	Cell-Matrix Adhesion	44:63	Cell-Matrix Adhesion	44:63	An Interplay Between Reaction-Diffusion and Cell-Matrix Adhesion Regulates Multiscale Invasion in Early Breast Carcinomatosis.
31456688	3	85	theme	experimental	687:698	arg1	assay					700:704	pathotypic experimental assay	676:704	pathotypic experimental assay	676:704	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	2	86	theme	such	440:443	arg1	interactions					445:456	such interactions	440:456	such interactions	440:456	A quantitative understanding of the relative contribution of such interactions to phenotypes associated with cancer cells can be arrived at through the construction of increasingly complex experimental and computational models.
31456688	4	87	theme	End	893:895	arg1	point					897:901	End point and time-lapse microscopic observations	893:941	point	897:901	End point and time-lapse microscopic observations of this assay allow us to study the earliest steps of cancer invasion as well as the dynamical interactions between the epithelial and stromal compartments.
31456688	3	88	dep	tumor	791:795	arg1	disseminating					797:809	disseminating	797:809	disseminating	797:809	Herein, we introduce a multiscale three-dimensional (3D) organo- and pathotypic experimental assay that approximates, to an unprecedented extent, the histopathological complexity of a tumor disseminating into its surrounding stromal milieu via both bulk and solitary motility dynamics.
31456688	7	89	theme	experimental	1636:1647	arg1	counterparts					1649:1660	the experimental counterparts	1632:1660	the experimental counterparts	1632:1660	The trained computational model successfully predicts phenotypes of the experimental counterparts that are subjected to pharmacological treatments (inhibition of N-linked glycosylation and matrix metalloproteinase activity) and scaffold modulation (alteration of collagen density).
31456688	1	90	theme	stromal	291:297	arg1	cells					299:303	surrounding untransformed but affected stromal cells	252:303	surrounding untransformed but affected stromal cells	252:303	The progression of cancer in the breast involves multiple reciprocal interactions between malignantly transformed epithelia, surrounding untransformed but affected stromal cells, and the extracellular matrix (ECM) that is remodeled during the process.
31302509	7	0	gly	glycosylation	990:1002	arg2	site					1004:1007	an N-linked glycosylation site	978:1007	an N-linked glycosylation site	978:1007	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	5	1	dep	shared	821:826	arg1	unrecognized					840:851	unrecognized	840:851	unrecognized	840:851	Mutation of the cow and hamster XPR1 genes identified a shared, previously unrecognized receptor-critical site.
31302509	8	2	theme	glycosylated	1190:1201	arg1	cofactor					1203:1210	an unidentified glycosylated cofactor	1174:1210	an unidentified glycosylated cofactor	1174:1210	Our data also suggest that an unidentified glycosylated cofactor may influence X/P-MLV entry.
31302509	4	3	theme	entry	701:705	arg1	restrictions					707:718	some entry restrictions	696:718	some entry restrictions	696:718	These restrictive receptors have replacement mutations in regions implicated in receptor function, and some entry restrictions can be relieved by glycosylation inhibitors.
31302509	5	4	theme	cow	781:783	arg1	Mutation					765:772	Mutation	765:772	Mutation of the cow and hamster XPR1 genes	765:806	Mutation of the cow and hamster XPR1 genes identified a shared, previously unrecognized receptor-critical site.
31302509	0	5	from	analysis	11:18	arg1	species					113:119	six mammalian species	99:119	six mammalian species	99:119	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	7	6	theme	XPR1	1010:1013	arg1	receptors					1015:1023	XPR1 receptors	1010:1023	XPR1 receptors	1010:1023	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	4	7	theme	glycosylation	739:751	arg1	inhibitors					753:762	glycosylation inhibitors	739:762	glycosylation inhibitors	739:762	These restrictive receptors have replacement mutations in regions implicated in receptor function, and some entry restrictions can be relieved by glycosylation inhibitors.
31302509	6	8	theme	G/Q503N	882:888	arg1	replacement					890:900	This G/Q503N replacement	877:900	This G/Q503N replacement	877:900	This G/Q503N replacement dramatically improves receptor function.
31302509	2	9	theme	XPR1	290:293	arg1	receptor					295:302	the XPR1 receptor	286:302	the XPR1 receptor for cell entry	286:317	X/P-MLVs use the XPR1 receptor for cell entry, and tropism differences are due to polymorphisms in XPR1 and the viral envelope.
31302509	1	10	theme	mammalian	254:262	arg1	species					264:270	mammalian species	254:270	mammalian species	254:270	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	0	11	theme	mammalian	103:111	arg1	species					113:119	six mammalian species	99:119	six mammalian species	99:119	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	3	12	theme	mammalian	530:538	arg1	species					540:546	six mammalian species	526:546	six mammalian species that restrict different subsets of X/P-MLVs	526:590	To characterize these receptor variants and identify blocks to cross-species transmission, we examined the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs.
31302509	6	13	theme	receptor	924:931	arg1	function					933:940	receptor function	924:940	receptor function	924:940	This G/Q503N replacement dramatically improves receptor function.
31302509	4	14	theme	replacement	626:636	arg1	mutations					638:646	replacement mutations	626:646	replacement mutations	626:646	These restrictive receptors have replacement mutations in regions implicated in receptor function, and some entry restrictions can be relieved by glycosylation inhibitors.
31302509	5	15	theme	genes	802:806	arg1	Mutation					765:772	Mutation	765:772	Mutation of the cow and hamster XPR1 genes	765:806	Mutation of the cow and hamster XPR1 genes identified a shared, previously unrecognized receptor-critical site.
31302509	7	16	theme	N-linked	981:988	arg1	site					1004:1007	an N-linked glycosylation site	978:1007	an N-linked glycosylation site	978:1007	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	1	17	theme	xenotropic	168:177	arg1	X/P-MLVs					218:225	X/P-MLVs	218:225	X/P-MLVs	218:225	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	17	theme	xenotropic	168:177	arg1	viruses					209:215	the xenotropic and polytropic mouse leukemia viruses	164:215	the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs)	164:226	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	17	theme	xenotropic	168:177	arg1	infectious					240:249	infectious	240:249	infectious	240:249	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	0	18	from	sensitivity	38:48	arg1	species					113:119	six mammalian species	99:119	six mammalian species	99:119	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	7	19	theme	glycosylation	990:1002	arg1	site					1004:1007	an N-linked glycosylation site	978:1007	an N-linked glycosylation site	978:1007	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	2	20	theme	cell	308:311	arg1	entry					313:317	cell entry	308:317	cell entry	308:317	X/P-MLVs use the XPR1 receptor for cell entry, and tropism differences are due to polymorphisms in XPR1 and the viral envelope.
31302509	0	21	theme	Mutational	0:9	arg1	analysis					11:18	Mutational analysis	0:18	Mutational analysis	0:18	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	3	22	theme	different	562:570	arg1	subsets					572:578	different subsets	562:578	different subsets of X/P-MLVs	562:590	To characterize these receptor variants and identify blocks to cross-species transmission, we examined the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs.
31302509	1	23	theme	polytropic	183:192	arg1	X/P-MLVs					218:225	X/P-MLVs	218:225	X/P-MLVs	218:225	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	23	theme	polytropic	183:192	arg1	viruses					209:215	the xenotropic and polytropic mouse leukemia viruses	164:215	the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs)	164:226	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	23	theme	polytropic	183:192	arg1	infectious					240:249	infectious	240:249	infectious	240:249	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	0	24	theme	glycosylation	24:36	arg1	sensitivity					38:48	glycosylation sensitivity	24:48	glycosylation sensitivity	24:48	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	7	25	gly	glycosylated	1033:1044	arg1	receptors					1015:1023	XPR1 receptors	1010:1023	XPR1 receptors	1010:1023	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	5	26	theme	XPR1	797:800	arg1	genes					802:806	the cow and hamster XPR1 genes	777:806	genes	802:806	Mutation of the cow and hamster XPR1 genes identified a shared, previously unrecognized receptor-critical site.
31302509	1	27	theme	mouse	194:198	arg1	X/P-MLVs					218:225	X/P-MLVs	218:225	X/P-MLVs	218:225	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	27	theme	mouse	194:198	arg1	viruses					209:215	the xenotropic and polytropic mouse leukemia viruses	164:215	the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs)	164:226	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	27	theme	mouse	194:198	arg1	infectious					240:249	infectious	240:249	infectious	240:249	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	28	from	species	264:270	arg1	viruses					209:215	the xenotropic and polytropic mouse leukemia viruses	164:215	the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs)	164:226	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	28	from	species	264:270	arg1	infectious					240:249	infectious	240:249	infectious	240:249	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	29	theme	Most	122:125	arg1	viruses					127:133	Most viruses	122:133	Most viruses	122:133	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	8	30	gly	glycosylated	1190:1201	arg1	cofactor					1203:1210	an unidentified glycosylated cofactor	1174:1210	an unidentified glycosylated cofactor	1174:1210	Our data also suggest that an unidentified glycosylated cofactor may influence X/P-MLV entry.
31302509	1	31	theme	leukemia	200:207	arg1	X/P-MLVs					218:225	X/P-MLVs	218:225	X/P-MLVs	218:225	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	31	theme	leukemia	200:207	arg1	viruses					209:215	the xenotropic and polytropic mouse leukemia viruses	164:215	the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs)	164:226	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	31	theme	leukemia	200:207	arg1	infectious					240:249	infectious	240:249	infectious	240:249	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	1	32	from	infectious	240:249	arg1	species					264:270	mammalian species	254:270	mammalian species	254:270	Most viruses infect only a few hosts, but the xenotropic and polytropic mouse leukemia viruses (X/P-MLVs) are broadly infectious in mammalian species.
31302509	5	33	theme	receptor-critical	853:869	arg1	site					871:874	a shared, previously unrecognized receptor-critical site	819:874	a shared, previously unrecognized receptor-critical site	819:874	Mutation of the cow and hamster XPR1 genes identified a shared, previously unrecognized receptor-critical site.
31302509	3	34	theme	X/P-MLVs	583:590	arg1	subsets					572:578	different subsets	562:578	different subsets of X/P-MLVs	562:590	To characterize these receptor variants and identify blocks to cross-species transmission, we examined the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs.
31302509	4	35	theme	receptor	673:680	arg1	function					682:689	receptor function	673:689	receptor function	673:689	These restrictive receptors have replacement mutations in regions implicated in receptor function, and some entry restrictions can be relieved by glycosylation inhibitors.
31302509	2	36	theme	viral	385:389	arg1	envelope					391:398	the viral envelope	381:398	the viral envelope	381:398	X/P-MLVs use the XPR1 receptor for cell entry, and tropism differences are due to polymorphisms in XPR1 and the viral envelope.
31302509	5	37	theme	hamster	789:795	arg1	genes					802:806	the cow and hamster XPR1 genes	777:806	genes	802:806	Mutation of the cow and hamster XPR1 genes identified a shared, previously unrecognized receptor-critical site.
31302509	7	38	theme	glycosylation	1132:1144	arg1	interface					1105:1113	the virus-receptor interface	1086:1113	the virus-receptor interface independently of glycosylation	1086:1144	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	8	39	theme	X/P-MLV	1226:1232	arg1	entry					1234:1238	X/P-MLV entry	1226:1238	X/P-MLV entry	1226:1238	Our data also suggest that an unidentified glycosylated cofactor may influence X/P-MLV entry.
31302509	5	40	theme	shared	821:826	arg1	site					871:874	a shared, previously unrecognized receptor-critical site	819:874	a shared, previously unrecognized receptor-critical site	819:874	Mutation of the cow and hamster XPR1 genes identified a shared, previously unrecognized receptor-critical site.
31302509	0	41	theme	XPR1	65:68	arg1	receptors					86:94	restrictive XPR1 gammaretrovirus receptors	53:94	restrictive XPR1 gammaretrovirus receptors	53:94	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	8	42	theme	unidentified	1177:1188	arg1	cofactor					1203:1210	an unidentified glycosylated cofactor	1174:1210	an unidentified glycosylated cofactor	1174:1210	Our data also suggest that an unidentified glycosylated cofactor may influence X/P-MLV entry.
31302509	2	43	from	polymorphisms	355:367	arg1	XPR1					372:375	XPR1	372:375	XPR1	372:375	X/P-MLVs use the XPR1 receptor for cell entry, and tropism differences are due to polymorphisms in XPR1 and the viral envelope.
31302509	2	43	from	polymorphisms	355:367	arg1	envelope					391:398	the viral envelope	381:398	the viral envelope	381:398	X/P-MLVs use the XPR1 receptor for cell entry, and tropism differences are due to polymorphisms in XPR1 and the viral envelope.
31302509	2	44	theme	tropism	324:330	arg1	differences					332:342	tropism differences	324:342	tropism differences	324:342	X/P-MLVs use the XPR1 receptor for cell entry, and tropism differences are due to polymorphisms in XPR1 and the viral envelope.
31302509	0	45	theme	restrictive	53:63	arg1	receptors					86:94	restrictive XPR1 gammaretrovirus receptors	53:94	restrictive XPR1 gammaretrovirus receptors	53:94	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	4	46	theme	restrictive	599:609	arg1	receptors					611:619	These restrictive receptors	593:619	These restrictive receptors	593:619	These restrictive receptors have replacement mutations in regions implicated in receptor function, and some entry restrictions can be relieved by glycosylation inhibitors.
31302509	7	47	theme	virus-receptor	1090:1103	arg1	interface					1105:1113	the virus-receptor interface	1086:1113	the virus-receptor interface independently of glycosylation	1086:1144	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	4	48	contain	have	621:624	arg1	receptors					611:619	These restrictive receptors	593:619	These restrictive receptors	593:619	These restrictive receptors have replacement mutations in regions implicated in receptor function, and some entry restrictions can be relieved by glycosylation inhibitors.
31302509	4	48	contain	have	621:624	arg2	mutations					638:646	replacement mutations	626:646	replacement mutations	626:646	These restrictive receptors have replacement mutations in regions implicated in receptor function, and some entry restrictions can be relieved by glycosylation inhibitors.
31302509	3	49	theme	cross-species	464:476	arg1	transmission					478:489	cross-species transmission	464:489	cross-species transmission	464:489	To characterize these receptor variants and identify blocks to cross-species transmission, we examined the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs.
31302509	0	50	theme	receptors	86:94	arg1	analysis					11:18	Mutational analysis	0:18	Mutational analysis	0:18	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	0	50	theme	receptors	86:94	arg1	sensitivity					38:48	glycosylation sensitivity	24:48	glycosylation sensitivity	24:48	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	3	51	theme	receptor	423:430	arg1	variants					432:439	these receptor variants	417:439	these receptor variants	417:439	To characterize these receptor variants and identify blocks to cross-species transmission, we examined the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs.
31302509	7	52	link	N-linked	981:988	arg1	site					1004:1007	an N-linked glycosylation site	978:1007	an N-linked glycosylation site	978:1007	While this substitution introduces an N-linked glycosylation site, XPR1 receptors are not glycosylated indicating that this replacement alters the virus-receptor interface independently of glycosylation.
31302509	0	53	theme	gammaretrovirus	70:84	arg1	receptors					86:94	restrictive XPR1 gammaretrovirus receptors	53:94	restrictive XPR1 gammaretrovirus receptors	53:94	Mutational analysis and glycosylation sensitivity of restrictive XPR1 gammaretrovirus receptors in six mammalian species.
31302509	3	54	theme	XPR1	508:511	arg1	receptors					513:521	the XPR1 receptors	504:521	the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs	504:590	To characterize these receptor variants and identify blocks to cross-species transmission, we examined the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs.
31302509	3	55	from	receptors	513:521	arg1	species					540:546	six mammalian species	526:546	six mammalian species that restrict different subsets of X/P-MLVs	526:590	To characterize these receptor variants and identify blocks to cross-species transmission, we examined the XPR1 receptors in six mammalian species that restrict different subsets of X/P-MLVs.
29609090	6	0	from	preference	986:995	arg1	NGT					1028:1030	the NGT	1024:1030	the NGT of Actinobacillus pleuropneumoniae (ApNGT)	1024:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	0	1	from	Aggregatibacter	27:41	arg1	N-Glycosyltransferase					0:20	N-Glycosyltransferase	0:20	N-Glycosyltransferase from Aggregatibacter aphrophilus	0:53	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	7	2	theme	synthesized	1105:1115	arg1	peptides					1117:1124	diverse synthesized peptides	1097:1124	diverse synthesized peptides	1097:1124	In vitro assays with diverse synthesized peptides revealed that AaNGT preferred different peptide substrates from ApNGT.
29609090	6	3	theme	pleuropneumoniae	1050:1065	arg1	NGT					1028:1030	the NGT	1024:1030	the NGT of Actinobacillus pleuropneumoniae (ApNGT)	1024:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	0	4	theme	donor	121:125	arg1	selectivity					127:137	relaxed nucleotide-activated sugar donor selectivity	86:137	relaxed nucleotide-activated sugar donor selectivity	86:137	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	6	5	theme	position-specific	960:976	arg1	preference					986:995	a different position-specific residue preference	948:995	a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT)	948:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	1	6	theme	unusual	211:217	arg1	pathway					219:225	an unusual pathway	208:225	an unusual pathway of N-linked protein glycosylation	208:259	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	7	theme	N-	316:317	arg1	sequon					308:313	the consensus sequon	294:313	the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides	294:355	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	7	theme	N-	316:317	arg1	-T/S					323:326	N-(X≠P)-T/S	316:326	N-(X≠P)-T/S	316:326	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	0	8	dep	Aggregatibacter	27:41	arg1	aphrophilus					43:53	Aggregatibacter aphrophilus	27:53	Aggregatibacter aphrophilus	27:53	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	4	9	theme	sugar	664:668	arg1	UDP-Gal					697:703	UDP-Gal	697:703	UDP-Gal	697:703	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	9	theme	sugar	664:668	arg1	UDP-Xyl					706:712	UDP-Xyl	706:712	UDP-Xyl	706:712	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	9	theme	sugar	664:668	arg1	UDP-GlcN					737:744	UDP-GlcN	737:744	UDP-GlcN	737:744	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	9	theme	sugar	664:668	arg1	donors					670:675	nucleotide-activated sugar donors	643:675	nucleotide-activated sugar donors	643:675	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	9	theme	sugar	664:668	arg1	UDP-Glc					688:694	UDP-Glc	688:694	UDP-Glc	688:694	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	9	theme	sugar	664:668	arg1	GDP-Glc					715:721	GDP-Glc	715:721	GDP-Glc	715:721	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	9	theme	sugar	664:668	arg1	dGDP-Glc					724:731	dGDP-Glc	724:731	dGDP-Glc	724:731	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	10	theme	tested	766:771	arg1	peptides					773:780	the tested peptides	762:780	the tested peptides	762:780	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	1	11	theme	X≠P	319:321	arg1	sequon					308:313	the consensus sequon	294:313	the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides	294:355	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	11	theme	X≠P	319:321	arg1	-T/S					323:326	N-(X≠P)-T/S	316:326	N-(X≠P)-T/S	316:326	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	12	link	N-linked	230:237	arg1	glycosylation					247:259	N-linked protein glycosylation	230:259	N-linked protein glycosylation	230:259	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	3	13	theme	Mass	485:488	arg1	Spectrometry					490:501	Mass Spectrometry	485:501	Mass Spectrometry	485:501	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	4	14	theme	nucleotide-activated	643:662	arg1	UDP-Gal					697:703	UDP-Gal	697:703	UDP-Gal	697:703	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	14	theme	nucleotide-activated	643:662	arg1	UDP-Xyl					706:712	UDP-Xyl	706:712	UDP-Xyl	706:712	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	14	theme	nucleotide-activated	643:662	arg1	UDP-GlcN					737:744	UDP-GlcN	737:744	UDP-GlcN	737:744	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	14	theme	nucleotide-activated	643:662	arg1	donors					670:675	nucleotide-activated sugar donors	643:675	nucleotide-activated sugar donors	643:675	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	14	theme	nucleotide-activated	643:662	arg1	UDP-Glc					688:694	UDP-Glc	688:694	UDP-Glc	688:694	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	14	theme	nucleotide-activated	643:662	arg1	GDP-Glc					715:721	GDP-Glc	715:721	GDP-Glc	715:721	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	14	theme	nucleotide-activated	643:662	arg1	dGDP-Glc					724:731	dGDP-Glc	724:731	dGDP-Glc	724:731	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	3	15	theme	substrate	585:593	arg1	specificities					595:607	its substrate specificities	581:607	its substrate specificities	581:607	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	5	16	theme	asparagine	906:915	arg1	residues					917:924	asparagine residues	906:924	asparagine residues	906:924	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	5	17	theme	identified	833:842	arg1	AaNGT					813:817	AaNGT	813:817	AaNGT	813:817	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	5	17	theme	identified	833:842	arg1	glycosyltransferase					852:870	the first identified natural glycosyltransferase	823:870	the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues	823:924	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	8	18	theme	short	1236:1240	arg1	peptides					1242:1249	natural short peptides	1228:1249	natural short peptides	1228:1249	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	7	19	theme	peptide	1166:1172	arg1	substrates					1174:1183	different peptide substrates	1156:1183	different peptide substrates from ApNGT	1156:1194	In vitro assays with diverse synthesized peptides revealed that AaNGT preferred different peptide substrates from ApNGT.
29609090	8	20	theme	natural	1228:1234	arg1	peptides					1242:1249	natural short peptides	1228:1249	natural short peptides	1228:1249	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	3	21	used	used	508:511	arg2	RP-HPLC					473:479	RP-HPLC	473:479	RP-HPLC	473:479	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	3	21	used	used	508:511	arg2	Spectrometry					490:501	Mass Spectrometry	485:501	Mass Spectrometry	485:501	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	1	22	theme	N-linked	230:237	arg1	glycosylation					247:259	N-linked protein glycosylation	230:259	N-linked protein glycosylation	230:259	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	5	23	theme	natural	844:850	arg1	AaNGT					813:817	AaNGT	813:817	AaNGT	813:817	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	5	23	theme	natural	844:850	arg1	glycosyltransferase					852:870	the first identified natural glycosyltransferase	823:870	the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues	823:924	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	6	24	theme	Actinobacillus	1035:1048	arg1	ApNGT					1068:1072	ApNGT	1068:1072	ApNGT	1068:1072	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	6	24	theme	Actinobacillus	1035:1048	arg1	pleuropneumoniae					1050:1065	Actinobacillus pleuropneumoniae	1035:1065	Actinobacillus pleuropneumoniae (ApNGT)	1035:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	1	25	gly	glycosylates	265:276	arg1	polypeptides					278:289	polypeptides	278:289	polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides	278:355	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	8	26	gly	N-glycoproteins	1323:1337	arg1	N-glycoproteins					1323:1337	important therapeutic mammalian N-glycoproteins	1291:1337	important therapeutic mammalian N-glycoproteins	1291:1337	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	3	27	gly	glycopeptide	535:546	arg2	glycopeptide					535:546	glycopeptide formation	535:556	glycopeptide formation by AaNGT	535:565	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	8	28	theme	peptides	1242:1249	arg1	glycosylation					1211:1223	The efficient glycosylation	1197:1223	The efficient glycosylation of natural short peptides by AaNGT	1197:1258	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	1	29	theme	protein	239:245	arg1	glycosylation					247:259	N-linked protein glycosylation	230:259	N-linked protein glycosylation	230:259	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	8	30	theme	important	1291:1299	arg1	N-glycoproteins					1323:1337	important therapeutic mammalian N-glycoproteins	1291:1337	important therapeutic mammalian N-glycoproteins	1291:1337	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	4	31	gly	glycosylate	750:760	arg1	peptides					773:780	the tested peptides	762:780	the tested peptides	762:780	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	1	32	theme	glycosylation	247:259	arg1	pathway					219:225	an unusual pathway	208:225	an unusual pathway of N-linked protein glycosylation	208:259	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	5	33	theme	able	872:875	arg1	AaNGT					813:817	AaNGT	813:817	AaNGT	813:817	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	5	33	theme	able	872:875	arg1	glycosyltransferase					852:870	the first identified natural glycosyltransferase	823:870	the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues	823:924	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	7	34	theme	different	1156:1164	arg1	substrates					1174:1183	different peptide substrates	1156:1183	different peptide substrates from ApNGT	1156:1194	In vitro assays with diverse synthesized peptides revealed that AaNGT preferred different peptide substrates from ApNGT.
29609090	6	35	theme	residue	978:984	arg1	preference					986:995	a different position-specific residue preference	948:995	a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT)	948:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	8	36	theme	mammalian	1313:1321	arg1	N-glycoproteins					1323:1337	important therapeutic mammalian N-glycoproteins	1291:1337	important therapeutic mammalian N-glycoproteins	1291:1337	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	7	37	from	ApNGT	1190:1194	arg1	substrates					1174:1183	different peptide substrates	1156:1183	different peptide substrates from ApNGT	1156:1194	In vitro assays with diverse synthesized peptides revealed that AaNGT preferred different peptide substrates from ApNGT.
29609090	8	38	gly	glycosylation	1211:1223	arg1	peptides					1242:1249	natural short peptides	1228:1249	natural short peptides	1228:1249	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	5	39	theme	GlcN	889:892	arg1	moiety					894:899	GlcN moiety	889:899	GlcN moiety	889:899	To the best of our knowledge, AaNGT was the first identified natural glycosyltransferase able to transfer GlcN moiety onto asparagine residues.
29609090	8	40	theme	therapeutic	1301:1311	arg1	N-glycoproteins					1323:1337	important therapeutic mammalian N-glycoproteins	1291:1337	important therapeutic mammalian N-glycoproteins	1291:1337	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
29609090	1	41	theme	hexose	334:339	arg1	monosaccharides					341:355	hexose monosaccharides	334:355	hexose monosaccharides	334:355	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	0	42	theme	relaxed	86:92	arg1	selectivity					127:137	relaxed nucleotide-activated sugar donor selectivity	86:137	relaxed nucleotide-activated sugar donor selectivity	86:137	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	6	43	theme	peptides	1010:1017	arg1	preference					986:995	a different position-specific residue preference	948:995	a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT)	948:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	1	44	from	polypeptides	278:289	arg1	sequon					308:313	the consensus sequon	294:313	the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides	294:355	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	44	from	polypeptides	278:289	arg1	-T/S					323:326	N-(X≠P)-T/S	316:326	N-(X≠P)-T/S	316:326	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	3	45	theme	glycopeptide	535:546	arg1	formation					548:556	glycopeptide formation	535:556	glycopeptide formation by AaNGT	535:565	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	6	46	theme	different	950:958	arg1	preference					986:995	a different position-specific residue preference	948:995	a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT)	948:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	6	47	theme	substrate	1000:1008	arg1	peptides					1010:1017	substrate peptides	1000:1017	substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT)	1000:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	6	48	from	NGT	1028:1030	arg1	peptides					1010:1017	substrate peptides	1000:1017	substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT)	1000:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	6	48	from	NGT	1028:1030	arg1	preference					986:995	a different position-specific residue preference	948:995	a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT)	948:1073	AaNGT also exhibited a different position-specific residue preference of substrate peptides from the NGT of Actinobacillus pleuropneumoniae (ApNGT).
29609090	7	49	theme	diverse	1097:1103	arg1	peptides					1117:1124	diverse synthesized peptides	1097:1124	diverse synthesized peptides	1097:1124	In vitro assays with diverse synthesized peptides revealed that AaNGT preferred different peptide substrates from ApNGT.
29609090	2	50	dep	Aggregatibacter	430:444	arg1	aphrophilus					446:456	Aggregatibacter aphrophilus	430:456	Aggregatibacter aphrophilus (named AaNGT)	430:470	Here, we expressed and characterized a novel N-glycosyltransferase from Aggregatibacter aphrophilus (named AaNGT).
29609090	7	51	theme	In vitro	1076:1083	arg1	assays					1085:1090	In vitro assays	1076:1090	In vitro assays with diverse synthesized peptides	1076:1124	In vitro assays with diverse synthesized peptides revealed that AaNGT preferred different peptide substrates from ApNGT.
29609090	7	52	with	assays	1085:1090	arg1	peptides					1117:1124	diverse synthesized peptides	1097:1124	diverse synthesized peptides	1097:1124	In vitro assays with diverse synthesized peptides revealed that AaNGT preferred different peptide substrates from ApNGT.
29609090	3	53	dep	used	508:511	arg1	assay					516:520	assay	516:520	assay	516:520	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	3	53	dep	used	508:511	arg1	quantify					526:533	quantify	526:533	quantify glycopeptide formation by AaNGT	526:565	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	3	53	dep	used	508:511	arg1	determine					571:579	determine	571:579	determine its substrate specificities	571:607	RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities.
29609090	0	54	gly	glycopeptides	67:79	arg2	glycopeptides					67:79	glycopeptides	67:79	glycopeptides with relaxed nucleotide-activated sugar donor selectivity	67:137	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	1	55	theme	inverting	174:182	arg1	N-Glycosyltransferase					140:160	N-Glycosyltransferase	140:160	N-Glycosyltransferase (NGT)	140:166	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	55	theme	inverting	174:182	arg1	glycosyltransferase					184:202	an inverting glycosyltransferase	171:202	an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation	171:259	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	4	56	theme	donors	670:675	arg1	UDP-Gal					697:703	UDP-Gal	697:703	UDP-Gal	697:703	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	56	theme	donors	670:675	arg1	UDP-Xyl					706:712	UDP-Xyl	706:712	UDP-Xyl	706:712	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	56	theme	donors	670:675	arg1	UDP-GlcN					737:744	UDP-GlcN	737:744	UDP-GlcN	737:744	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	56	theme	donors	670:675	arg1	donors					670:675	nucleotide-activated sugar donors	643:675	nucleotide-activated sugar donors	643:675	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	56	theme	donors	670:675	arg1	UDP-Glc					688:694	UDP-Glc	688:694	UDP-Glc	688:694	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	56	theme	donors	670:675	arg1	GDP-Glc					715:721	GDP-Glc	715:721	GDP-Glc	715:721	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	56	theme	donors	670:675	arg1	variety					632:638	a variety	630:638	a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN,	630:745	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	4	56	theme	donors	670:675	arg1	dGDP-Glc					724:731	dGDP-Glc	724:731	dGDP-Glc	724:731	AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides.
29609090	0	57	theme	sugar	115:119	arg1	selectivity					127:137	relaxed nucleotide-activated sugar donor selectivity	86:137	relaxed nucleotide-activated sugar donor selectivity	86:137	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	1	58	with	sequon	308:313	arg1	monosaccharides					341:355	hexose monosaccharides	334:355	hexose monosaccharides	334:355	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	59	theme	consensus	298:306	arg1	sequon					308:313	the consensus sequon	294:313	the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides	294:355	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	1	59	theme	consensus	298:306	arg1	-T/S					323:326	N-(X≠P)-T/S	316:326	N-(X≠P)-T/S	316:326	N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides.
29609090	0	60	theme	nucleotide-activated	94:113	arg1	selectivity					127:137	relaxed nucleotide-activated sugar donor selectivity	86:137	relaxed nucleotide-activated sugar donor selectivity	86:137	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	0	61	with	glycopeptides	67:79	arg1	selectivity					127:137	relaxed nucleotide-activated sugar donor selectivity	86:137	relaxed nucleotide-activated sugar donor selectivity	86:137	N-Glycosyltransferase from Aggregatibacter aphrophilus synthesizes glycopeptides with relaxed nucleotide-activated sugar donor selectivity.
29609090	2	62	theme	novel	397:401	arg1	N-glycosyltransferase					403:423	a novel N-glycosyltransferase	395:423	a novel N-glycosyltransferase	395:423	Here, we expressed and characterized a novel N-glycosyltransferase from Aggregatibacter aphrophilus (named AaNGT).
29609090	8	63	theme	efficient	1201:1209	arg1	glycosylation					1211:1223	The efficient glycosylation	1197:1223	The efficient glycosylation of natural short peptides by AaNGT	1197:1258	The efficient glycosylation of natural short peptides by AaNGT showed its potential to modify important therapeutic mammalian N-glycoproteins.
30181805	7	0	theme	molecular	1519:1527	arg1	mechanisms					1529:1538	the molecular mechanisms	1515:1538	the molecular mechanisms underlying trastuzumab treatment in BC	1515:1577	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	4	1	theme	down-regulated	987:1000	arg1	genes					1002:1006	1053 down-regulated genes	982:1006	1053 down-regulated genes	982:1006	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	4	2	theme	N-linked	903:910	arg1	glycosylation					912:924	protein N-linked glycosylation	895:924	protein N-linked glycosylation via asparagine	895:939	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	3	3	theme	pathway	627:633	arg1	analyses					653:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses	560:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses	560:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	7	4	theme	BC	1665:1666	arg1	treatment					1652:1660	the treatment	1648:1660	the treatment of BC	1648:1666	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	7	5	theme	identified	1456:1465	arg1	genes					1480:1484	the identified DEGs and hub genes	1452:1484	the identified DEGs and hub genes	1452:1484	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	3	6	theme	Cytoscape	790:798	arg1	software					800:807	Cytoscape software	790:807	Cytoscape software	790:807	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	5	7	theme	hub	1137:1139	arg1	genes					1141:1145	Eight hub genes	1131:1145	Eight hub genes	1131:1145	Eight hub genes were identified from the PPI network, including GSK3B, RAC1, PXN, ERBB2, HSP90AA1, FGF2, PIK3R1 and RAC2.
30181805	0	8	from	Identification	0:13	arg1	cancer					88:93	breast cancer	81:93	breast cancer using bioinformatics analysis	81:123	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	3	9	theme	expressed	748:756	arg1	genes					758:762	the differentially expressed genes	729:762	the differentially expressed genes (DEGs)	729:769	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	3	9	theme	expressed	748:756	arg1	DEGs					765:768	DEGs	765:768	DEGs	765:768	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	0	10	theme	breast	81:86	arg1	cancer					88:93	breast cancer	81:93	breast cancer using bioinformatics analysis	81:123	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	2	11	theme	potential	538:546	arg1	mechanisms					548:557	their potential mechanisms	532:557	their potential mechanisms	532:557	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	7	12	theme	mechanisms	1529:1538	arg1	understanding					1498:1510	our understanding	1494:1510	our understanding of the molecular mechanisms underlying trastuzumab treatment in BC	1494:1577	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	3	13	theme	genes	758:762	arg1	network					718:724	a protein-protein interaction (PPI) network	682:724	a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs)	682:769	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	0	14	theme	bioinformatics	101:114	arg1	analysis					116:123	bioinformatics analysis	101:123	bioinformatics analysis	101:123	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	7	15	theme	hub	1476:1478	arg1	genes					1480:1484	the identified DEGs and hub genes	1452:1484	the identified DEGs and hub genes	1452:1484	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	3	16	dep	ontology	569:576	arg1	GO					579:580	GO	579:580	GO	579:580	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	4	17	theme	DNA	878:880	arg1	replication					882:892	DNA replication	878:892	DNA replication	878:892	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	0	18	from	genes	35:39	arg1	cancer					88:93	breast cancer	81:93	breast cancer using bioinformatics analysis	81:123	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	2	19	theme	cancer	354:359	arg1	samples					361:367	154 operable early-stage breast cancer samples	322:367	154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120)	322:460	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	6	20	theme	cancer	1332:1337	arg1	tissues					1339:1345	breast cancer tissues	1325:1345	breast cancer tissues	1325:1345	Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin.
30181805	6	21	theme	experimental	1257:1268	arg1	results					1270:1276	Our experimental results	1253:1276	Our experimental results	1253:1276	Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin.
30181805	4	22	theme	protein	895:901	arg1	glycosylation					912:924	protein N-linked glycosylation	895:924	protein N-linked glycosylation via asparagine	895:939	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	4	23	theme	plasma	1064:1069	arg1	membrane					1071:1078	plasma membrane	1064:1078	plasma membrane	1064:1078	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	2	24	theme	breast	347:352	arg1	samples					361:367	154 operable early-stage breast cancer samples	322:367	154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120)	322:460	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	6	25	theme	breast	1325:1330	arg1	tissues					1339:1345	breast cancer tissues	1325:1345	breast cancer tissues	1325:1345	Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin.
30181805	7	26	theme	molecular	1627:1635	arg1	GSK3B					1595:1599	GSK3B	1595:1599	GSK3B	1595:1599	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	7	26	theme	molecular	1627:1635	arg1	target					1637:1642	a molecular target	1625:1642	a molecular target for the treatment of BC	1625:1666	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	2	27	theme	Omnibus	283:289	arg1	database					297:304	the Gene Expression Omnibus (GEO) database	263:304	the Gene Expression Omnibus (GEO) database	263:304	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	7	28	theme	trastuzumab	1551:1561	arg1	treatment					1563:1571	trastuzumab treatment	1551:1571	trastuzumab treatment	1551:1571	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	1	29	theme	leading	159:165	arg1	causes					167:172	the leading causes	155:172	the leading causes of death among women worldwide	155:203	Breast cancer (BC) is one of the leading causes of death among women worldwide.
30181805	0	30	theme	pathways	22:29	arg1	Identification					0:13	Identification	0:13	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.	0:124	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	3	31	theme	gene	564:567	arg1	KEGG					636:639	KEGG	636:639	KEGG	636:639	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	3	31	theme	gene	564:567	arg1	ontology					569:576	The gene ontology	560:576	The gene ontology (GO)	560:581	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	2	32	theme	trastuzumab	498:508	arg1	treatment					510:518	trastuzumab treatment	498:518	trastuzumab treatment	498:518	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	6	33	dep	β-catenin	1393:1401	arg1	as					1386:1387	as	1386:1387	as	1386:1387	Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin.
30181805	6	33	dep	β-catenin	1393:1401	arg1	was					1389:1391	was	1389:1391	was	1389:1391	Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin.
30181805	2	34	theme	Expression	272:281	arg1	database					297:304	the Gene Expression Omnibus (GEO) database	263:304	the Gene Expression Omnibus (GEO) database	263:304	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	4	35	theme	axon	1025:1028	arg1	guidance					1030:1037	axon guidance	1025:1037	axon guidance	1025:1037	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	1	36	theme	causes	167:172	arg1	one					148:150	one	148:150	one	148:150	Breast cancer (BC) is one of the leading causes of death among women worldwide.
30181805	1	36	theme	causes	167:172	arg1	causes					167:172	the leading causes	155:172	the leading causes of death among women worldwide	155:203	Breast cancer (BC) is one of the leading causes of death among women worldwide.
30181805	0	37	dep	treatment	68:76	arg1	response					44:51	response	44:51	response	44:51	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	4	38	link	N-linked	903:910	arg1	glycosylation					912:924	protein N-linked glycosylation	895:924	protein N-linked glycosylation via asparagine	895:939	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	2	39	theme	Gene	267:270	arg1	database					297:304	the Gene Expression Omnibus (GEO) database	263:304	the Gene Expression Omnibus (GEO) database	263:304	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	4	40	theme	protein	1040:1046	arg1	localization					1048:1059	protein localization	1040:1059	protein localization to plasma membrane	1040:1078	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	2	41	theme	neoadjuvant	382:392	arg1	capecitabine					394:405	neoadjuvant capecitabine plus docetaxel	382:420	capecitabine	394:405	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	0	42	theme	genes	35:39	arg1	Identification					0:13	Identification	0:13	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.	0:124	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	3	43	theme	Encyclopedia	593:604	arg1	pathway					627:633	Kyoto Encyclopedia of Genes and Genomes pathway	587:633	Kyoto Encyclopedia of Genes and Genomes pathway	587:633	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	2	44	theme	early-stage	335:345	arg1	samples					361:367	154 operable early-stage breast cancer samples	322:367	154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120)	322:460	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	1	45	theme	death	177:181	arg1	causes					167:172	the leading causes	155:172	the leading causes of death among women worldwide	155:203	Breast cancer (BC) is one of the leading causes of death among women worldwide.
30181805	0	46	theme	key	18:20	arg1	pathways					22:29	key pathways	18:29	key pathways	18:29	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	3	47	theme	PPI	713:715	arg1	network					718:724	a protein-protein interaction (PPI) network	682:724	a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs)	682:769	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	2	48	theme	gene	475:478	arg1	signatures					480:489	gene signatures	475:489	gene signatures during trastuzumab treatment	475:518	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	4	49	theme	protein	1108:1114	arg1	glycosylation					1116:1128	protein glycosylation	1108:1128	protein glycosylation	1108:1128	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	4	50	theme	toxic	958:962	arg1	substances					964:973	toxic substances	958:973	toxic substances	958:973	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	3	51	theme	protein-protein	684:698	arg1	network					718:724	a protein-protein interaction (PPI) network	682:724	a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs)	682:769	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	3	52	theme	enrichment	642:651	arg1	analyses					653:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses	560:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses	560:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	4	53	theme	up-regulated	847:858	arg1	genes					860:864	1231 up-regulated genes	842:864	1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances	842:973	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	3	54	theme	interaction	700:710	arg1	network					718:724	a protein-protein interaction (PPI) network	682:724	a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs)	682:769	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	3	55	theme	ontology	569:576	arg1	analyses					653:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses	560:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses	560:660	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	3	56	theme	Genomes	619:625	arg1	pathway					627:633	Kyoto Encyclopedia of Genes and Genomes pathway	587:633	Kyoto Encyclopedia of Genes and Genomes pathway	587:633	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	1	57	theme	Breast	126:131	arg1	BC					141:142	BC	141:142	BC	141:142	Breast cancer (BC) is one of the leading causes of death among women worldwide.
30181805	1	57	theme	Breast	126:131	arg1	cancer					133:138	Breast cancer	126:138	Breast cancer (BC)	126:143	Breast cancer (BC) is one of the leading causes of death among women worldwide.
30181805	1	58	theme	women	189:193	arg1	worldwide					195:203	women worldwide	189:203	women worldwide	189:203	Breast cancer (BC) is one of the leading causes of death among women worldwide.
30181805	0	59	from	cancer	88:93	arg1	Identification					0:13	Identification	0:13	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.	0:124	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	7	60	used	used	1617:1620	arg2	GSK3B					1595:1599	GSK3B	1595:1599	GSK3B	1595:1599	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	7	60	used	used	1617:1620	arg2	target					1637:1642	a molecular target	1625:1642	a molecular target for the treatment of BC	1625:1666	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	4	61	theme	protein	1081:1087	arg1	stabilization					1089:1101	protein stabilization	1081:1101	protein stabilization	1081:1101	There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation.
30181805	2	62	theme	GEO	292:294	arg1	database					297:304	the Gene Expression Omnibus (GEO) database	263:304	the Gene Expression Omnibus (GEO) database	263:304	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	6	63	theme	poor	1371:1374	arg1	survival					1376:1383	poor survival	1371:1383	poor survival	1371:1383	Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was β-catenin.
30181805	0	64	theme	trastuzumab	56:66	arg1	treatment					68:76	trastuzumab treatment	56:76	trastuzumab treatment	56:76	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	3	65	theme	Genes	609:613	arg1	Genomes					619:625	Genomes	619:625	Genomes	619:625	The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software.
30181805	2	66	theme	expression	215:224	arg1	profile					226:232	The gene expression profile GSE22358	206:241	The gene expression profile GSE22358	206:241	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	2	67	theme	operable	326:333	arg1	samples					361:367	154 operable early-stage breast cancer samples	322:367	154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120)	322:460	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	7	68	theme	present	1423:1429	arg1	study					1431:1435	the present study	1419:1435	the present study	1419:1435	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	0	69	from	pathways	22:29	arg1	cancer					88:93	breast cancer	81:93	breast cancer using bioinformatics analysis	81:123	Identification of key pathways and genes in response to trastuzumab treatment in breast cancer using bioinformatics analysis.
30181805	2	70	theme	gene	210:213	arg1	profile					226:232	The gene expression profile GSE22358	206:241	The gene expression profile GSE22358	206:241	The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms.
30181805	7	71	theme	DEGs	1467:1470	arg1	genes					1480:1484	the identified DEGs and hub genes	1452:1484	the identified DEGs and hub genes	1452:1484	In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.
30181805	5	72	theme	PPI	1172:1174	arg1	network					1176:1182	the PPI network	1168:1182	the PPI network	1168:1182	Eight hub genes were identified from the PPI network, including GSK3B, RAC1, PXN, ERBB2, HSP90AA1, FGF2, PIK3R1 and RAC2.
31527085	3	0	theme	multiple	333:340	arg1	sites					351:355	multiple O-GlcNAc sites	333:355	multiple O-GlcNAc sites	333:355	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	1	1	theme	different	172:180	arg1	roles					182:186	different roles	172:186	different roles	172:186	O-GlcNAcylation is a ubiquitous protein glycosylation playing different roles on variant proteins.
31527085	7	2	theme	repeat	847:852	arg1	domain					854:859	the tetratricopeptide repeat domain	825:859	the tetratricopeptide repeat domain in sOGT	825:867	We identified six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT, with Thr12 and Ser56 being two "key" sites.
31527085	3	3	theme	O-GlcNAc	342:349	arg1	sites					351:355	multiple O-GlcNAc sites	333:355	multiple O-GlcNAc sites	333:355	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	3	4	located	observed	367:374	arg1	sOGT					395:398	sOGT	395:398	sOGT	395:398	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	3	4	located	observed	367:374	arg1	OGT					390:392	short-form OGT	379:392	short-form OGT (sOGT)	379:399	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	3	4	located	observed	367:374	arg1	OGT					423:425	nucleocytoplasmic OGT	405:425	nucleocytoplasmic OGT (ncOGT)	405:433	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	3	4	located	observed	367:374	arg1	ncOGT					428:432	ncOGT	428:432	ncOGT	428:432	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	3	4	located	observed	367:374	arg2	sites					351:355	multiple O-GlcNAc sites	333:355	multiple O-GlcNAc sites	333:355	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	7	5	from	sites	816:820	arg1	domain					854:859	the tetratricopeptide repeat domain	825:859	the tetratricopeptide repeat domain in sOGT	825:867	We identified six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT, with Thr12 and Ser56 being two "key" sites.
31527085	4	6	theme	amino	546:550	arg1	ncOGT					534:538	ncOGT	534:538	ncOGT (1036 amino acids)	534:557	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	4	6	theme	amino	546:550	arg1	acids					552:556	1036 amino acids	541:556	1036 amino acids	541:556	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	8	7	theme	pulldown	1081:1088	arg1	assays					1090:1095	pulldown assays	1081:1095	pulldown assays	1081:1095	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	0	8	from	O-GlcNAcylation	0:14	arg1	sOGT					67:70	sOGT	67:70	sOGT	67:70	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	0	8	from	O-GlcNAcylation	0:14	arg1	transferase					54:64	short-form O-GlcNAc transferase	34:64	short-form O-GlcNAc transferase (sOGT)	34:71	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	10	9	theme	cell	1460:1463	arg1	progression					1471:1481	cell cycle progression	1460:1481	cell cycle progression	1460:1481	By proteomic and bioinformatics analyses, we found that T12A and S56A differed in substrate proteins (e.g. HNRNPU and PDCD6IP), which eventually affected cell cycle progression and/or cell proliferation.
31527085	6	10	theme	O-GlcNAcylation	759:773	arg1	site					775:778	the major O-GlcNAcylation site	749:778	the major O-GlcNAcylation site on sOGT	749:786	Here, we performed LC-MS/MS and mutational analyses to seek the major O-GlcNAcylation site on sOGT.
31527085	2	11	theme	nucleocytoplasmic	295:311	arg1	proteins					313:320	nucleocytoplasmic proteins	295:320	nucleocytoplasmic proteins	295:320	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	5	12	from	roles	659:663	arg1	sOGT					668:671	sOGT	668:671	sOGT	668:671	To date, the major O-GlcNAcylation sites and their roles in sOGT remain unknown.
31527085	0	13	theme	substrate	87:95	arg1	selectivity					97:107	its substrate selectivity	83:107	its substrate selectivity	83:107	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	5	14	theme	major	621:625	arg1	sites					643:647	the major O-GlcNAcylation sites	617:647	the major O-GlcNAcylation sites	617:647	To date, the major O-GlcNAcylation sites and their roles in sOGT remain unknown.
31527085	6	15	theme	major	753:757	arg1	site					775:778	the major O-GlcNAcylation site	749:778	the major O-GlcNAcylation site on sOGT	749:786	Here, we performed LC-MS/MS and mutational analyses to seek the major O-GlcNAcylation site on sOGT.
31527085	7	16	theme	O-GlcNAc	807:814	arg1	sites					816:820	six O-GlcNAc sites	803:820	six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT	803:867	We identified six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT, with Thr12 and Ser56 being two "key" sites.
31527085	10	17	dep	HNRNPU	1413:1418	arg1	e.g.					1408:1411	e.g.	1408:1411	e.g.	1408:1411	By proteomic and bioinformatics analyses, we found that T12A and S56A differed in substrate proteins (e.g. HNRNPU and PDCD6IP), which eventually affected cell cycle progression and/or cell proliferation.
31527085	10	18	theme	substrate	1388:1396	arg1	proteins					1398:1405	substrate proteins	1388:1405	substrate proteins (e.g. HNRNPU and PDCD6IP)	1388:1431	By proteomic and bioinformatics analyses, we found that T12A and S56A differed in substrate proteins (e.g. HNRNPU and PDCD6IP), which eventually affected cell cycle progression and/or cell proliferation.
31527085	12	19	from	Thr12	1695:1699	arg1	role					1668:1671	the regulatory role	1653:1671	the regulatory role of O-GlcNAcylation at Thr12 and Ser56	1653:1709	The data also highlight the regulatory role of O-GlcNAcylation at Thr12 and Ser56.
31527085	12	20	from	Ser56	1705:1709	arg1	role					1668:1671	the regulatory role	1653:1671	the regulatory role of O-GlcNAcylation at Thr12 and Ser56	1653:1709	The data also highlight the regulatory role of O-GlcNAcylation at Thr12 and Ser56.
31527085	10	21	theme	cycle	1465:1469	arg1	progression					1471:1481	cell cycle progression	1460:1481	cell cycle progression	1460:1481	By proteomic and bioinformatics analyses, we found that T12A and S56A differed in substrate proteins (e.g. HNRNPU and PDCD6IP), which eventually affected cell cycle progression and/or cell proliferation.
31527085	9	22	dep	T12A	1288:1291	arg1	contrast					1276:1283	contrast	1276:1283	contrast	1276:1283	In HEK293T cells, S56A bound to and hence glycosylated more proteins in contrast to T12A and WT sOGT.
31527085	8	23	theme	sOGT	1147:1150	arg1	activity					1152:1159	sOGT activity	1147:1159	sOGT activity	1147:1159	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	2	24	theme	sugar	277:281	arg1	addition					283:290	the sugar addition	273:290	the sugar addition to nucleocytoplasmic proteins	273:320	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	9	25	theme	WT	1297:1298	arg1	sOGT					1300:1303	WT sOGT	1297:1303	WT sOGT	1297:1303	In HEK293T cells, S56A bound to and hence glycosylated more proteins in contrast to T12A and WT sOGT.
31527085	1	26	theme	variant	191:197	arg1	proteins					199:206	variant proteins	191:206	variant proteins	191:206	O-GlcNAcylation is a ubiquitous protein glycosylation playing different roles on variant proteins.
31527085	9	27	theme	more	1259:1262	arg1	proteins					1264:1271	more proteins	1259:1271	more proteins	1259:1271	In HEK293T cells, S56A bound to and hence glycosylated more proteins in contrast to T12A and WT sOGT.
31527085	8	28	dep	Thr12In	1054:1060	arg1	vitro					1062:1066	vitro	1062:1066	vitro	1062:1066	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	3	29	from	nucleus	464:470	arg1	cell					489:492	cell	489:492	cell	489:492	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	7	30	from	domain	854:859	arg1	sOGT					864:867	sOGT	864:867	sOGT	864:867	We identified six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT, with Thr12 and Ser56 being two "key" sites.
31527085	6	31	from	site	775:778	arg1	sOGT					783:786	sOGT	783:786	sOGT	783:786	Here, we performed LC-MS/MS and mutational analyses to seek the major O-GlcNAcylation site on sOGT.
31527085	11	32	theme	sOGT	1568:1571	arg1	selectivity					1583:1593	sOGT substrate selectivity	1568:1593	sOGT substrate selectivity	1568:1593	These findings demonstrate that O-GlcNAcylation modulates sOGT substrate selectivity and affects its role in the cell.
31527085	8	33	theme	Ser56	984:988	arg1	modification					968:979	the modification	964:979	the modification of Ser56	964:988	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	8	34	theme	O-GlcNAcylation	934:948	arg1	site					950:953	a dominant O-GlcNAcylation site	923:953	a dominant O-GlcNAcylation site	923:953	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	8	34	theme	O-GlcNAcylation	934:948	arg1	Thr12					914:918	Thr12	914:918	Thr12	914:918	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	8	35	theme	sOGT-interacting	1177:1192	arg1	proteins					1194:1201	sOGT-interacting proteins	1177:1201	sOGT-interacting proteins	1177:1201	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	11	36	from	role	1611:1614	arg1	cell					1623:1626	the cell	1619:1626	the cell	1619:1626	These findings demonstrate that O-GlcNAcylation modulates sOGT substrate selectivity and affects its role in the cell.
31527085	12	37	theme	O-GlcNAcylation	1676:1690	arg1	role					1668:1671	the regulatory role	1653:1671	the regulatory role of O-GlcNAcylation at Thr12 and Ser56	1653:1709	The data also highlight the regulatory role of O-GlcNAcylation at Thr12 and Ser56.
31527085	3	38	from	cytoplasm	476:484	arg1	cell					489:492	cell	489:492	cell	489:492	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	10	39	theme	bioinformatics	1323:1336	arg1	analyses					1338:1345	proteomic and bioinformatics analyses	1309:1345	analyses	1338:1345	By proteomic and bioinformatics analyses, we found that T12A and S56A differed in substrate proteins (e.g. HNRNPU and PDCD6IP), which eventually affected cell cycle progression and/or cell proliferation.
31527085	0	40	theme	Thr12/Ser56	19:29	arg1	O-GlcNAcylation					0:14	O-GlcNAcylation	0:14	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT)	0:71	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	12	41	theme	regulatory	1657:1666	arg1	role					1668:1671	the regulatory role	1653:1671	the regulatory role of O-GlcNAcylation at Thr12 and Ser56	1653:1709	The data also highlight the regulatory role of O-GlcNAcylation at Thr12 and Ser56.
31527085	4	42	theme	HeLa	596:599	arg1	cells					601:605	HeLa cells	596:605	HeLa cells	596:605	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	0	43	theme	O-GlcNAc	45:52	arg1	sOGT					67:70	sOGT	67:70	sOGT	67:70	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	0	43	theme	O-GlcNAc	45:52	arg1	transferase					54:64	short-form O-GlcNAc transferase	34:64	short-form O-GlcNAc transferase (sOGT)	34:71	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	2	44	theme	unique	243:248	arg1	transferase					218:228	O-GlcNAc transferase	209:228	O-GlcNAc transferase (OGT)	209:234	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	2	44	theme	unique	243:248	arg1	enzyme					250:255	the unique enzyme	239:255	the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins	239:320	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	0	45	theme	short-form	34:43	arg1	sOGT					67:70	sOGT	67:70	sOGT	67:70	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	0	45	theme	short-form	34:43	arg1	transferase					54:64	short-form O-GlcNAc transferase	34:64	short-form O-GlcNAc transferase (sOGT)	34:71	O-GlcNAcylation of Thr12/Ser56 in short-form O-GlcNAc transferase (sOGT) regulates its substrate selectivity.
31527085	11	46	theme	substrate	1573:1581	arg1	selectivity					1583:1593	sOGT substrate selectivity	1568:1593	sOGT substrate selectivity	1568:1593	These findings demonstrate that O-GlcNAcylation modulates sOGT substrate selectivity and affects its role in the cell.
31527085	8	47	theme	dominant	925:932	arg1	site					950:953	a dominant O-GlcNAcylation site	923:953	a dominant O-GlcNAcylation site	923:953	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	8	47	theme	dominant	925:932	arg1	Thr12					914:918	Thr12	914:918	Thr12	914:918	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	4	48	from	O-GlcNAcylation	505:519	arg1	ncOGT					534:538	ncOGT	534:538	ncOGT (1036 amino acids)	534:557	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	4	48	from	O-GlcNAcylation	505:519	arg1	acids					552:556	1036 amino acids	541:556	1036 amino acids	541:556	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	10	49	theme	cell	1490:1493	arg1	proliferation					1495:1507	cell proliferation	1490:1507	cell proliferation	1490:1507	By proteomic and bioinformatics analyses, we found that T12A and S56A differed in substrate proteins (e.g. HNRNPU and PDCD6IP), which eventually affected cell cycle progression and/or cell proliferation.
31527085	5	50	theme	O-GlcNAcylation	627:641	arg1	sites					643:647	the major O-GlcNAcylation sites	617:647	the major O-GlcNAcylation sites	617:647	To date, the major O-GlcNAcylation sites and their roles in sOGT remain unknown.
31527085	10	51	theme	proteomic	1309:1317	arg1	analyses					1338:1345	proteomic and bioinformatics analyses	1309:1345	analyses	1338:1345	By proteomic and bioinformatics analyses, we found that T12A and S56A differed in substrate proteins (e.g. HNRNPU and PDCD6IP), which eventually affected cell cycle progression and/or cell proliferation.
31527085	3	52	theme	nucleocytoplasmic	405:421	arg1	ncOGT					428:432	ncOGT	428:432	ncOGT	428:432	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	3	52	theme	nucleocytoplasmic	405:421	arg1	OGT					423:425	nucleocytoplasmic OGT	405:425	nucleocytoplasmic OGT (ncOGT)	405:433	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	4	53	theme	Ser389	524:529	arg1	O-GlcNAcylation					505:519	O-GlcNAcylation	505:519	O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids)	505:557	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	8	54	theme	sOGT	1017:1020	arg1	O-GlcNAcylation					1022:1036	sOGT O-GlcNAcylation	1017:1036	sOGT O-GlcNAcylation	1017:1036	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	6	55	theme	mutational	721:730	arg1	analyses					732:739	mutational analyses	721:739	mutational analyses	721:739	Here, we performed LC-MS/MS and mutational analyses to seek the major O-GlcNAcylation site on sOGT.
31527085	7	56	theme	key	902:904	arg1	"					905:905	"key"	901:905	two "key" sites	897:911	We identified six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT, with Thr12 and Ser56 being two "key" sites.
31527085	1	57	theme	ubiquitous	131:140	arg1	glycosylation					150:162	a ubiquitous protein glycosylation	129:162	a ubiquitous protein glycosylation playing different roles on variant proteins	129:206	O-GlcNAcylation is a ubiquitous protein glycosylation playing different roles on variant proteins.
31527085	1	57	theme	ubiquitous	131:140	arg1	O-GlcNAcylation					110:124	O-GlcNAcylation	110:124	O-GlcNAcylation	110:124	O-GlcNAcylation is a ubiquitous protein glycosylation playing different roles on variant proteins.
31527085	4	58	theme	nuclear	571:577	arg1	translocation					579:591	its nuclear translocation	567:591	its nuclear translocation in HeLa cells	567:605	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	9	59	theme	HEK293T	1207:1213	arg1	cells					1215:1219	HEK293T cells	1207:1219	HEK293T cells	1207:1219	In HEK293T cells, S56A bound to and hence glycosylated more proteins in contrast to T12A and WT sOGT.
31527085	1	60	theme	protein	142:148	arg1	glycosylation					150:162	a ubiquitous protein glycosylation	129:162	a ubiquitous protein glycosylation playing different roles on variant proteins	129:206	O-GlcNAcylation is a ubiquitous protein glycosylation playing different roles on variant proteins.
31527085	1	60	theme	protein	142:148	arg1	O-GlcNAcylation					110:124	O-GlcNAcylation	110:124	O-GlcNAcylation	110:124	O-GlcNAcylation is a ubiquitous protein glycosylation playing different roles on variant proteins.
31527085	8	61	theme	Thr12In	1054:1060	arg1	activity					1068:1075	Thr12In vitro activity	1054:1075	Thr12In vitro activity	1054:1075	Thr12 is a dominant O-GlcNAcylation site, whereas the modification of Ser56 plays a role in regulating sOGT O-GlcNAcylation, partly through Thr12In vitro activity and pulldown assays demonstrated that O-GlcNAcylation does not affect sOGT activity but does affect sOGT-interacting proteins.
31527085	2	62	theme	O-GlcNAc	209:216	arg1	transferase					218:228	O-GlcNAc transferase	209:228	O-GlcNAc transferase (OGT)	209:234	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	2	62	theme	O-GlcNAc	209:216	arg1	enzyme					250:255	the unique enzyme	239:255	the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins	239:320	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	2	62	theme	O-GlcNAc	209:216	arg1	OGT					231:233	OGT	231:233	OGT	231:233	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	2	63	theme	responsible	257:267	arg1	transferase					218:228	O-GlcNAc transferase	209:228	O-GlcNAc transferase (OGT)	209:234	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	2	63	theme	responsible	257:267	arg1	enzyme					250:255	the unique enzyme	239:255	the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins	239:320	O-GlcNAc transferase (OGT) is the unique enzyme responsible for the sugar addition to nucleocytoplasmic proteins.
31527085	4	64	from	translocation	579:591	arg1	cells					601:605	HeLa cells	596:605	HeLa cells	596:605	Moreover, O-GlcNAcylation of Ser389 in ncOGT (1036 amino acids) affects its nuclear translocation in HeLa cells.
31527085	5	65	from	sites	643:647	arg1	sOGT					668:671	sOGT	668:671	sOGT	668:671	To date, the major O-GlcNAcylation sites and their roles in sOGT remain unknown.
31527085	7	66	theme	"	905:905	arg1	sites					907:911	two "key" sites	897:911	two "key" sites	897:911	We identified six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT, with Thr12 and Ser56 being two "key" sites.
31527085	7	67	theme	tetratricopeptide	829:845	arg1	domain					854:859	the tetratricopeptide repeat domain	825:859	the tetratricopeptide repeat domain in sOGT	825:867	We identified six O-GlcNAc sites in the tetratricopeptide repeat domain in sOGT, with Thr12 and Ser56 being two "key" sites.
31527085	3	68	theme	short-form	379:388	arg1	sOGT					395:398	sOGT	395:398	sOGT	395:398	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31527085	3	68	theme	short-form	379:388	arg1	OGT					390:392	short-form OGT	379:392	short-form OGT (sOGT)	379:399	Recently, multiple O-GlcNAc sites have been observed on short-form OGT (sOGT) and nucleocytoplasmic OGT (ncOGT), both of which locate in the nucleus and cytoplasm in cell.
31266803	0	0	theme	carbohydrate	107:118	arg1	antigens					120:127	host-derived carbohydrate antigens	94:127	host-derived carbohydrate antigens	94:127	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	6	1	theme	glycan	1350:1355	arg1	deconstruction					1330:1343	the complete deconstruction	1317:1343	the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes	1317:1413	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	1	2	theme	opportunistic	181:193	arg1	pneumoniae					228:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	4	3	theme	crystallography	856:870	arg1	studies					872:878	X-ray crystallography studies	850:878	X-ray crystallography studies combined with functional assays	850:910	X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif.
31266803	1	4	theme	host	284:287	arg1	glycans					289:295	harvest host glycans	276:295	harvest host glycans	276:295	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	0	5	theme	host-derived	94:105	arg1	antigens					120:127	host-derived carbohydrate antigens	94:127	host-derived carbohydrate antigens	94:127	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	6	6	theme	individual	1216:1225	arg1	activities					1239:1248	the individual or combined activities	1212:1248	the individual or combined activities of these enzymes	1212:1265	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	1	7	theme	bacterial	195:203	arg1	pneumoniae					228:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	3	8	theme	α-	808:809	arg1	linkages					826:833	α-(1→3/4) and α-(1→2) fucosidic linkages	794:833	linkages	826:833	Here, we identified two pneumococcal enzymes, SpGH29C and SpGH95C, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively.
31266803	5	9	theme	LewisY	1087:1092	arg1	antigens					1105:1112	LewisY and LewisB antigens	1087:1112	LewisY and LewisB antigens	1087:1112	Together, these enzymes could defucosylate LewisY and LewisB antigens in a complementary fashion.
31266803	2	10	theme	O-linked	374:381	arg1	glycans					383:389	O-linked glycans	374:389	O-linked glycans	374:389	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	0	11	theme	antigens	120:127	arg1	degradation					79:89	complete degradation	70:89	complete degradation of host-derived carbohydrate antigens	70:127	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	7	12	dep	capacity	1476:1483	arg1	process					1505:1511	process	1505:1511	to process host glycans	1502:1524	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	6	13	theme	combined	1230:1237	arg1	activities					1239:1248	the individual or combined activities	1212:1248	the individual or combined activities of these enzymes	1212:1265	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	4	14	theme	LewisX	965:970	arg1	motifs					980:985	the LewisA and LewisX antigen motifs	950:985	motifs	980:985	X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif.
31266803	7	15	theme	likely	1534:1539	arg1	roles					1541:1545	the likely roles	1530:1545	the likely roles of α-fucosidases in this	1530:1570	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	6	16	theme	complete	1321:1328	arg1	deconstruction					1330:1343	the complete deconstruction	1317:1343	the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes	1317:1413	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	2	17	link	O-linked	374:381	arg1	glycans					383:389	O-linked glycans	374:389	O-linked glycans	374:389	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	8	18	theme	interaction	1870:1880	arg1	models					1837:1842	more refined models	1824:1842	more refined models of the S. pneumoniae-host interaction	1824:1880	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	8	19	theme	pneumococcal	1648:1659	arg1	virulence					1661:1669	pneumococcal virulence	1648:1669	pneumococcal virulence	1648:1669	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	1	20	theme	pathogen	205:212	arg1	pneumoniae					228:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	8	21	theme	enzymes	1606:1612	arg1	importance					1592:1601	the importance	1588:1601	the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92	1588:1728	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	0	22	from	pneumoniae	51:60	arg1	α-fucosidases					18:30	Two complementary α-fucosidases	0:30	Two complementary α-fucosidases from Streptococcus pneumoniae	0:60	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	2	23	theme	fucosylated	626:636	arg1	antigens					685:692	histo-blood group antigens	667:692	histo-blood group antigens	667:692	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	23	theme	fucosylated	626:636	arg1	glycans					638:644	fucosylated glycans	626:644	fucosylated glycans	626:644	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	24	attach	linked	466:471	arg2	glycans					348:354	complex glycans	340:354	complex glycans	340:354	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	24	attach	linked	466:471	arg1	virulence					480:488	the virulence	476:488	the virulence of S. pneumoniae	476:505	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	24	attach	linked	466:471	arg2	glycans					383:389	O-linked glycans	374:389	O-linked glycans	374:389	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	24	attach	linked	466:471	arg2	ability					442:448	an ability	439:448	an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown	439:712	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	24	attach	linked	466:471	arg2	N-					367:368	N-	367:368	N-	367:368	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	7	25	from	α-fucosidases	1550:1562	arg1	this					1567:1570	this	1567:1570	this	1567:1570	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	1	26	theme	Streptococcus	214:226	arg1	pneumoniae					228:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	the opportunistic bacterial pathogen Streptococcus pneumoniae	177:237	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	0	27	theme	complementary	4:16	arg1	α-fucosidases					18:30	Two complementary α-fucosidases	0:30	Two complementary α-fucosidases from Streptococcus pneumoniae	0:60	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	2	28	theme	pneumoniae	496:505	arg1	virulence					480:488	the virulence	476:488	the virulence of S. pneumoniae	476:505	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	29	theme	glycans	348:354	arg1	N-					367:368	N-	367:368	N-	367:368	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	29	theme	glycans	348:354	arg1	glycans					383:389	O-linked glycans	374:389	O-linked glycans	374:389	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	29	theme	glycans	348:354	arg1	ability					442:448	an ability	439:448	an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown	439:712	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	29	theme	glycans	348:354	arg1	variety					329:335	a variety	327:335	a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown	327:712	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	29	theme	glycans	348:354	arg1	glycans					348:354	complex glycans	340:354	complex glycans	340:354	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	5	30	gly	defucosylate	1074:1085	arg1	antigens					1105:1112	LewisY and LewisB antigens	1087:1112	LewisY and LewisB antigens	1087:1112	Together, these enzymes could defucosylate LewisY and LewisB antigens in a complementary fashion.
31266803	2	31	dep	use	542:544	arg1	unknown					706:712	unknown	706:712	unknown	706:712	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	31	dep	use	542:544	arg1	glycome					599:605	the human glycome	589:605	the human glycome	589:605	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	32	theme	group	679:683	arg1	antigens					685:692	histo-blood group antigens	667:692	histo-blood group antigens	667:692	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	32	theme	group	679:683	arg1	glycans					638:644	fucosylated glycans	626:644	fucosylated glycans	626:644	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	33	theme	complex	340:346	arg1	N-					367:368	N-	367:368	N-	367:368	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	33	theme	complex	340:346	arg1	glycans					383:389	O-linked glycans	374:389	O-linked glycans	374:389	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	33	theme	complex	340:346	arg1	ability					442:448	an ability	439:448	an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown	439:712	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	33	theme	complex	340:346	arg1	glycans					348:354	complex glycans	340:354	complex glycans	340:354	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	5	34	theme	complementary	1119:1131	arg1	fashion					1133:1139	a complementary fashion	1117:1139	a complementary fashion	1117:1139	Together, these enzymes could defucosylate LewisY and LewisB antigens in a complementary fashion.
31266803	4	35	theme	functional	894:903	arg1	assays					905:910	functional assays	894:910	functional assays	894:910	X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif.
31266803	2	36	theme	histo-blood	667:677	arg1	antigens					685:692	histo-blood group antigens	667:692	histo-blood group antigens	667:692	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	36	theme	histo-blood	667:677	arg1	glycans					638:644	fucosylated glycans	626:644	fucosylated glycans	626:644	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	6	37	theme	pneumococcal	1394:1405	arg1	enzymes					1407:1413	pneumococcal enzymes	1394:1413	pneumococcal enzymes	1394:1413	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	2	38	theme	enzyme	562:567	arg1	machinery					569:577	a sophisticated enzyme machinery	546:577	a sophisticated enzyme machinery to attack	546:587	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	8	39	theme	neuraminidase	1684:1696	arg1	NanA					1698:1701	the neuraminidase NanA	1680:1701	the neuraminidase NanA	1680:1701	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	1	40	theme	important	133:141	arg1	aspect					143:148	An important aspect	130:148	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host	130:256	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	1	40	theme	important	133:141	arg1	ability					265:271	its ability	261:271	its ability to harvest host glycans	261:295	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	7	41	from	understanding	1445:1457	arg1	this					1567:1570	this	1567:1570	this	1567:1570	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	1	42	theme	human	247:251	arg1	host					253:256	its human host	243:256	its human host	243:256	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	4	43	theme	antigen	972:978	arg1	motifs					980:985	the LewisA and LewisX antigen motifs	950:985	motifs	980:985	X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif.
31266803	3	44	theme	pneumococcal	739:750	arg1	enzymes					752:758	two pneumococcal enzymes	735:758	two pneumococcal enzymes	735:758	Here, we identified two pneumococcal enzymes, SpGH29C and SpGH95C, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively.
31266803	3	44	theme	pneumococcal	739:750	arg1	SpGH95C					773:779	SpGH95C	773:779	SpGH95C	773:779	Here, we identified two pneumococcal enzymes, SpGH29C and SpGH95C, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively.
31266803	3	44	theme	pneumococcal	739:750	arg1	SpGH29C					761:767	SpGH29C	761:767	SpGH29C	761:767	Here, we identified two pneumococcal enzymes, SpGH29C and SpGH95C, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively.
31266803	2	45	theme	sophisticated	548:560	arg1	machinery					569:577	a sophisticated enzyme machinery	546:577	a sophisticated enzyme machinery to attack	546:587	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	8	46	theme	S.	1851:1852	arg1	interaction					1870:1880	the S. pneumoniae-host interaction	1847:1880	the S. pneumoniae-host interaction	1847:1880	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	8	47	theme	mannosidase	1711:1721	arg1	SpGH92					1723:1728	the mannosidase SpGH92	1707:1728	the mannosidase SpGH92	1707:1728	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	4	48	theme	-antigen	1028:1035	arg1	motif					1037:1041	the H(O)-antigen motif	1020:1041	the H(O)-antigen motif	1020:1041	X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif.
31266803	1	49	theme	host	253:256	arg1	aspect					143:148	An important aspect	130:148	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host	130:256	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	1	49	theme	host	253:256	arg1	ability					265:271	its ability	261:271	its ability to harvest host glycans	261:295	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	0	50	theme	Streptococcus	37:49	arg1	pneumoniae					51:60	Streptococcus pneumoniae	37:60	Streptococcus pneumoniae	37:60	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	2	51	dep	glycome	599:605	arg1	copes					615:619	copes	615:619	copes with fucosylated glycans, which are primarily histo-blood group antigens	615:692	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	6	52	theme	cascades	1188:1195	arg1	reconstruction					1151:1164	In vitro reconstruction	1142:1164	In vitro reconstruction of glycan degradation cascades	1142:1195	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	8	53	theme	refined	1829:1835	arg1	models					1837:1842	more refined models	1824:1842	more refined models of the S. pneumoniae-host interaction	1824:1880	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	0	54	theme	complete	70:77	arg1	degradation					79:89	complete degradation	70:89	complete degradation of host-derived carbohydrate antigens	70:127	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	5	55	theme	LewisB	1098:1103	arg1	antigens					1105:1112	LewisY and LewisB antigens	1087:1112	LewisY and LewisB antigens	1087:1112	Together, these enzymes could defucosylate LewisY and LewisB antigens in a complementary fashion.
31266803	2	56	theme	human	593:597	arg1	unknown					706:712	unknown	706:712	unknown	706:712	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	56	theme	human	593:597	arg1	glycome					599:605	the human glycome	589:605	the human glycome	589:605	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	7	57	theme	host	1513:1516	arg1	glycans					1518:1524	host glycans	1513:1524	host glycans	1513:1524	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	6	58	theme	degradation	1176:1186	arg1	cascades					1188:1195	glycan degradation cascades	1169:1195	glycan degradation cascades	1169:1195	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	0	59	link	host-derived	94:105	arg1	antigens					120:127	host-derived carbohydrate antigens	94:127	host-derived carbohydrate antigens	94:127	Two complementary α-fucosidases from Streptococcus pneumoniae promote complete degradation of host-derived carbohydrate antigens.
31266803	6	60	theme	glycan	1289:1294	arg1	structure					1296:1304	the underlying glycan structure	1274:1304	the underlying glycan structure	1274:1304	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	4	61	theme	X-ray	850:854	arg1	studies					872:878	X-ray crystallography studies	850:878	X-ray crystallography studies combined with functional assays	850:910	X-ray crystallography studies combined with functional assays revealed that SpGH29C is specific for the LewisA and LewisX antigen motifs and that SpGH95C is specific for the H(O)-antigen motif.
31266803	7	62	theme	pneumoniae	1491:1500	arg1	capacity					1476:1483	the extensive capacity	1462:1483	the extensive capacity of S. pneumoniae to process host glycans	1462:1524	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	6	63	theme	glycan	1169:1174	arg1	cascades					1188:1195	glycan degradation cascades	1169:1195	glycan degradation cascades	1169:1195	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	6	64	dep	In	1142:1143	arg1	vitro					1145:1149	vitro	1145:1149	vitro	1145:1149	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	8	65	theme	glycan	1628:1633	arg1	breakdown					1635:1643	glycan breakdown	1628:1643	glycan breakdown	1628:1643	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	6	66	theme	In	1142:1143	arg1	reconstruction					1151:1164	In vitro reconstruction	1142:1164	In vitro reconstruction of glycan degradation cascades	1142:1195	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	7	67	from	this	1567:1570	arg1	roles					1541:1545	the likely roles	1530:1545	the likely roles of α-fucosidases in this	1530:1570	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	7	67	from	this	1567:1570	arg1	understanding					1445:1457	our understanding	1441:1457	our understanding of the extensive capacity of S. pneumoniae to process host glycans	1441:1524	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	8	68	theme	important	1792:1800	arg1	α-fucosidases					1754:1766	the α-fucosidases	1750:1766	the α-fucosidases identified here	1750:1782	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	8	68	theme	important	1792:1800	arg1	factors					1802:1808	important factors	1792:1808	important factors	1792:1808	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	3	69	theme	fucosidic	816:824	arg1	linkages					826:833	α-(1→3/4) and α-(1→2) fucosidic linkages	794:833	linkages	826:833	Here, we identified two pneumococcal enzymes, SpGH29C and SpGH95C, that target α-(1→3/4) and α-(1→2) fucosidic linkages, respectively.
31266803	6	70	theme	enzymes	1259:1265	arg1	activities					1239:1248	the individual or combined activities	1212:1248	the individual or combined activities of these enzymes	1212:1265	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	1	71	theme	interaction	157:167	arg1	aspect					143:148	An important aspect	130:148	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host	130:256	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	1	71	theme	interaction	157:167	arg1	ability					265:271	its ability	261:271	its ability to harvest host glycans	261:295	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
31266803	7	72	theme	α-fucosidases	1550:1562	arg1	roles					1541:1545	the likely roles	1530:1545	the likely roles of α-fucosidases in this	1530:1570	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	7	72	theme	α-fucosidases	1550:1562	arg1	understanding					1445:1457	our understanding	1441:1457	our understanding of the extensive capacity of S. pneumoniae to process host glycans	1441:1524	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	7	73	theme	capacity	1476:1483	arg1	roles					1541:1545	the likely roles	1530:1545	the likely roles of α-fucosidases in this	1530:1570	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	7	73	theme	capacity	1476:1483	arg1	understanding					1445:1457	our understanding	1441:1457	our understanding of the extensive capacity of S. pneumoniae to process host glycans	1441:1524	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	7	74	from	roles	1541:1545	arg1	this					1567:1570	this	1567:1570	this	1567:1570	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	2	75	theme	carbohydrate	416:427	arg1	antigens					429:436	carbohydrate antigens	416:436	carbohydrate antigens	416:436	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	6	76	theme	underlying	1278:1287	arg1	structure					1296:1304	the underlying glycan structure	1274:1304	the underlying glycan structure	1274:1304	In vitro reconstruction of glycan degradation cascades disclosed that the individual or combined activities of these enzymes expose the underlying glycan structure, promoting the complete deconstruction of a glycan that would otherwise be resistant to pneumococcal enzymes.
31266803	7	77	theme	extensive	1466:1474	arg1	capacity					1476:1483	the extensive capacity	1462:1483	the extensive capacity of S. pneumoniae to process host glycans	1462:1524	These experiments expand our understanding of the extensive capacity of S. pneumoniae to process host glycans and the likely roles of α-fucosidases in this.
31266803	2	78	gly	fucosylated	626:636	arg1	antigens					685:692	histo-blood group antigens	667:692	histo-blood group antigens	667:692	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	2	78	gly	fucosylated	626:636	arg1	glycans					638:644	fucosylated glycans	626:644	fucosylated glycans	626:644	The pneumococcus can degrade a variety of complex glycans, including N- and O-linked glycans, glycosaminoglycans, and carbohydrate antigens, an ability that is tightly linked to the virulence of S. pneumoniae Although S. pneumoniae is known to use a sophisticated enzyme machinery to attack the human glycome, how it copes with fucosylated glycans, which are primarily histo-blood group antigens, is largely unknown.
31266803	8	79	theme	pneumoniae-host	1854:1868	arg1	interaction					1870:1880	the S. pneumoniae-host interaction	1847:1880	the S. pneumoniae-host interaction	1847:1880	Overall, given the importance of enzymes that initiate glycan breakdown in pneumococcal virulence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the α-fucosidases identified here will be important factors in developing more refined models of the S. pneumoniae-host interaction.
31266803	1	80	theme	harvest	276:282	arg1	glycans					289:295	harvest host glycans	276:295	harvest host glycans	276:295	An important aspect of the interaction between the opportunistic bacterial pathogen Streptococcus pneumoniae and its human host is its ability to harvest host glycans.
30793403	6	0	theme	O-GlcNAcylated	988:1001	arg1	proteins					1003:1010	O-GlcNAcylated proteins	988:1010	O-GlcNAcylated proteins	988:1010	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	8	1	from	maturation	1289:1298	arg1	COCs					1310:1313	bovine COCs	1303:1313	bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor	1303:1369	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	9	2	theme	meiotic	1528:1534	arg1	progression					1536:1546	meiotic progression	1528:1546	meiotic progression	1528:1546	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	9	3	from	increase	1408:1415	arg1	substrates					1435:1444	O-GlcNAcylated substrates	1420:1444	O-GlcNAcylated substrates	1420:1444	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	9	3	from	increase	1408:1415	arg1	cells					1462:1466	cumulus cells	1454:1466	cumulus cells	1454:1466	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	9	3	from	increase	1408:1415	arg1	oocyte					1476:1481	the oocyte	1472:1481	the oocyte	1472:1481	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	6	4	theme	nuclear	1037:1043	arg1	envelope					1045:1052	the nuclear envelope	1033:1052	the nuclear envelope	1033:1052	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	5	5	theme	multiple	797:804	arg1	proteins					821:828	multiple O-GlcNAcylated proteins	797:828	multiple O-GlcNAcylated proteins	797:828	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	10	6	theme	sperm	1685:1689	arg1	penetration					1691:1701	sperm penetration	1685:1701	sperm penetration	1685:1701	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	10	7	theme	sperm	1704:1708	arg1	decondensation					1715:1728	sperm head decondensation	1704:1728	sperm head decondensation	1704:1728	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	11	8	theme	proper	1763:1768	arg1	homeostasis					1779:1789	proper O-GlcNAc homeostasis	1763:1789	proper O-GlcNAc homeostasis during meiotic maturation	1763:1815	Thus, proper O-GlcNAc homeostasis during meiotic maturation is important for fertilization and pronuclear stage development.
30793403	6	9	from	spindles	1130:1137	arg1	prophase					1057:1064	prophase I	1057:1066	prophase I	1057:1066	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	6	9	from	spindles	1130:1137	arg1	OGA					1069:1071	OGA	1069:1071	OGA at the cortex throughout meiosis	1069:1104	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	6	9	from	spindles	1130:1137	arg1	OGT					1111:1113	OGT	1111:1113	OGT at the meiotic spindles	1111:1137	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	6	10	from	cortex	1080:1085	arg1	prophase					1057:1064	prophase I	1057:1066	prophase I	1057:1066	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	6	10	from	cortex	1080:1085	arg1	OGA					1069:1071	OGA	1069:1071	OGA at the cortex throughout meiosis	1069:1104	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	6	10	from	cortex	1080:1085	arg1	OGT					1111:1113	OGT	1111:1113	OGT at the meiotic spindles	1111:1137	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	2	11	theme	O-linked	322:329	arg1	residue					313:319	a single sugar residue	298:319	a single sugar residue (O-linked β-N-acetylglucosamine)	298:352	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	11	theme	O-linked	322:329	arg1	β-N-acetylglucosamine					331:351	O-linked β-N-acetylglucosamine	322:351	O-linked β-N-acetylglucosamine	322:351	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	9	12	theme	O-GlcNAcylated	1420:1433	arg1	substrates					1435:1444	O-GlcNAcylated substrates	1420:1444	O-GlcNAcylated substrates	1420:1444	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	11	13	theme	O-GlcNAc	1770:1777	arg1	homeostasis					1779:1789	proper O-GlcNAc homeostasis	1763:1789	proper O-GlcNAc homeostasis during meiotic maturation	1763:1815	Thus, proper O-GlcNAc homeostasis during meiotic maturation is important for fertilization and pronuclear stage development.
30793403	10	14	theme	COCs	1643:1646	arg1	fertilization					1626:1638	in vitro fertilization	1617:1638	in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation	1617:1754	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	8	15	theme	selective	1347:1355	arg1	inhibitor					1361:1369	a highly selective OGA inhibitor	1338:1369	a highly selective OGA inhibitor	1338:1369	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	8	15	theme	selective	1347:1355	arg1	Thiamet-G					1321:1329	Thiamet-G	1321:1329	Thiamet-G (TMG)	1321:1335	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	9	16	theme	cumulus	1507:1513	arg1	expansion					1515:1523	cumulus expansion	1507:1523	cumulus expansion	1507:1523	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	10	17	dep	in	1617:1618	arg1	vitro					1620:1624	vitro	1620:1624	vitro	1620:1624	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	4	18	theme	O-GlcNAcylation	652:666	arg1	dynamics					668:675	O-GlcNAcylation dynamics	652:675	O-GlcNAcylation dynamics in bovine and human oocytes during meiosis	652:718	Here we investigated O-GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation.
30793403	2	19	theme	residue	313:319	arg1	addition					286:293	O-GlcNAcylation-the addition	266:293	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.	266:494	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	10	20	theme	due	1663:1665	arg1	TMG					1659:1661	TMG	1659:1661	TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation	1659:1754	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	1	21	theme	mammalian	190:198	arg1	oocyte					200:205	the mammalian oocyte	186:205	the mammalian oocyte	186:205	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	1	21	theme	mammalian	190:198	arg1	susceptible					217:227	susceptible	217:227	susceptible	217:227	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	5	22	theme	O-GlcNAcylated	806:819	arg1	proteins					821:828	multiple O-GlcNAcylated proteins	797:828	multiple O-GlcNAcylated proteins	797:828	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	2	23	theme	sugar	307:311	arg1	residue					313:319	a single sugar residue	298:319	a single sugar residue (O-linked β-N-acetylglucosamine)	298:352	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	23	theme	sugar	307:311	arg1	β-N-acetylglucosamine					331:351	O-linked β-N-acetylglucosamine	322:351	O-linked β-N-acetylglucosamine	322:351	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	24	dep	addition	286:293	arg1	modification					389:400	a posttranslational modification	369:400	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.	266:494	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	24	dep	addition	286:293	arg1	function					467:474	the function	463:474	the function of oocyte proteins	463:493	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	24	dep	addition	286:293	arg1	sensor					435:440	a cellular nutrient sensor	415:440	a cellular nutrient sensor	415:440	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	7	25	theme	human	1199:1203	arg1	oocytes					1205:1211	human oocytes	1199:1211	human oocytes	1199:1211	These expression patterns were evolutionarily conserved in human oocytes.
30793403	1	26	theme	Meiotic	101:107	arg1	maturation					109:118	Meiotic maturation	101:118	Meiotic maturation	101:118	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	1	26	theme	Meiotic	101:107	arg1	processes					166:174	metabolically demanding processes	142:174	metabolically demanding processes	142:174	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	1	26	theme	Meiotic	101:107	arg1	fertilization					124:136	fertilization	124:136	fertilization	124:136	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	10	27	theme	in	1617:1618	arg1	fertilization					1626:1638	in vitro fertilization	1617:1638	in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation	1617:1754	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	8	28	theme	meiotic	1281:1287	arg1	maturation					1289:1298	meiotic maturation	1281:1298	meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor	1281:1369	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	5	29	theme	bovine	848:853	arg1	COCs					881:884	COCs	881:884	COCs	881:884	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	5	29	theme	bovine	848:853	arg1	complexes					870:878	bovine cumulus oocyte complexes	848:878	bovine cumulus oocyte complexes (COCs)	848:885	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	4	30	theme	perturbation	769:780	arg1	sequelae					753:760	the developmental sequelae	735:760	the developmental sequelae of its perturbation	735:780	Here we investigated O-GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation.
30793403	2	31	theme	nutrient	426:433	arg1	modification					389:400	a posttranslational modification	369:400	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.	266:494	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	31	theme	nutrient	426:433	arg1	function					467:474	the function	463:474	the function of oocyte proteins	463:493	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	31	theme	nutrient	426:433	arg1	sensor					435:440	a cellular nutrient sensor	415:440	a cellular nutrient sensor	415:440	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	32	theme	proteins	486:493	arg1	modification					389:400	a posttranslational modification	369:400	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.	266:494	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	32	theme	proteins	486:493	arg1	function					467:474	the function	463:474	the function of oocyte proteins	463:493	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	32	theme	proteins	486:493	arg1	sensor					435:440	a cellular nutrient sensor	415:440	a cellular nutrient sensor	415:440	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	8	33	theme	O-GlcNAc	1225:1232	arg1	function					1234:1241	O-GlcNAc function	1225:1241	O-GlcNAc function	1225:1241	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	5	34	theme	subcellular	969:979	arg1	sites					981:985	specific subcellular sites	960:985	specific subcellular sites	960:985	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	2	35	from	addition	286:293	arg1	proteins-is					357:367	proteins-is	357:367	proteins-is	357:367	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	36	theme	oocyte	479:484	arg1	proteins					486:493	oocyte proteins	479:493	oocyte proteins	479:493	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	37	link	O-linked	322:329	arg1	residue					313:319	a single sugar residue	298:319	a single sugar residue (O-linked β-N-acetylglucosamine)	298:352	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	37	link	O-linked	322:329	arg1	β-N-acetylglucosamine					331:351	O-linked β-N-acetylglucosamine	322:351	O-linked β-N-acetylglucosamine	322:351	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	5	38	theme	specific	960:967	arg1	sites					981:985	specific subcellular sites	960:985	specific subcellular sites	960:985	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	4	39	from	dynamics	668:675	arg1	oocytes					697:703	bovine and human oocytes	680:703	bovine and human oocytes during meiosis	680:718	Here we investigated O-GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation.
30793403	3	40	theme	O-GlcNAc	527:534	arg1	OGT					549:551	OGT	549:551	OGT	549:551	O-GlcNAcylation is mediated by O-GlcNAc transferase (OGT), which adds O-GlcNAc onto proteins, and O-GlcNAcase (OGA), which removes it.
30793403	3	40	theme	O-GlcNAc	527:534	arg1	transferase					536:546	O-GlcNAc transferase	527:546	O-GlcNAc transferase (OGT)	527:552	O-GlcNAcylation is mediated by O-GlcNAc transferase (OGT), which adds O-GlcNAc onto proteins, and O-GlcNAcase (OGA), which removes it.
30793403	0	41	theme	mammalian	42:50	arg1	maturation					67:76	mammalian oocyte meiotic maturation	42:76	mammalian oocyte meiotic maturation	42:76	Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization.
30793403	10	42	theme	head	1710:1713	arg1	decondensation					1715:1728	sperm head decondensation	1704:1728	sperm head decondensation	1704:1728	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	2	43	theme	O-GlcNAcylation-the	266:284	arg1	addition					286:293	O-GlcNAcylation-the addition	266:293	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.	266:494	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	4	44	theme	bovine	680:685	arg1	oocytes					697:703	bovine and human oocytes	680:703	bovine and human oocytes during meiosis	680:718	Here we investigated O-GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation.
30793403	4	45	theme	human	691:695	arg1	oocytes					697:703	bovine and human oocytes	680:703	bovine and human oocytes during meiosis	680:718	Here we investigated O-GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation.
30793403	11	46	theme	pronuclear	1852:1861	arg1	development					1869:1879	pronuclear stage development	1852:1879	pronuclear stage development	1852:1879	Thus, proper O-GlcNAc homeostasis during meiotic maturation is important for fertilization and pronuclear stage development.
30793403	11	47	theme	meiotic	1798:1804	arg1	maturation					1806:1815	meiotic maturation	1798:1815	meiotic maturation	1798:1815	Thus, proper O-GlcNAc homeostasis during meiotic maturation is important for fertilization and pronuclear stage development.
30793403	0	48	theme	homeostasis	23:33	arg1	Disruption					0:9	Disruption	0:9	Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation	0:76	Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization.
30793403	1	49	from	changes	232:238	arg1	availability					252:263	nutrient availability	243:263	nutrient availability	243:263	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	5	50	theme	cumulus	855:861	arg1	COCs					881:884	COCs	881:884	COCs	881:884	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	5	50	theme	cumulus	855:861	arg1	complexes					870:878	bovine cumulus oocyte complexes	848:878	bovine cumulus oocyte complexes (COCs)	848:885	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	0	51	theme	meiotic	59:65	arg1	maturation					67:76	mammalian oocyte meiotic maturation	42:76	mammalian oocyte meiotic maturation	42:76	Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization.
30793403	11	52	theme	stage	1863:1867	arg1	development					1869:1879	pronuclear stage development	1852:1879	pronuclear stage development	1852:1879	Thus, proper O-GlcNAc homeostasis during meiotic maturation is important for fertilization and pronuclear stage development.
30793403	8	53	theme	OGA	1357:1359	arg1	inhibitor					1361:1369	a highly selective OGA inhibitor	1338:1369	a highly selective OGA inhibitor	1338:1369	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	8	53	theme	OGA	1357:1359	arg1	Thiamet-G					1321:1329	Thiamet-G	1321:1329	Thiamet-G (TMG)	1321:1335	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	9	54	theme	cumulus	1454:1460	arg1	cells					1462:1466	cumulus cells	1454:1466	cumulus cells	1454:1466	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	0	55	theme	oocyte	52:57	arg1	maturation					67:76	mammalian oocyte meiotic maturation	42:76	mammalian oocyte meiotic maturation	42:76	Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization.
30793403	9	56	theme	dramatic	1399:1406	arg1	increase					1408:1415	a dramatic increase	1397:1415	a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte	1397:1481	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	4	57	theme	developmental	739:751	arg1	sequelae					753:760	the developmental sequelae	735:760	the developmental sequelae of its perturbation	735:780	Here we investigated O-GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation.
30793403	9	58	from	effect	1497:1502	arg1	expansion					1515:1523	cumulus expansion	1507:1523	cumulus expansion	1507:1523	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	9	58	from	effect	1497:1502	arg1	progression					1536:1546	meiotic progression	1528:1546	meiotic progression	1528:1546	Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression.
30793403	2	59	theme	single	300:305	arg1	residue					313:319	a single sugar residue	298:319	a single sugar residue (O-linked β-N-acetylglucosamine)	298:352	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	59	theme	single	300:305	arg1	β-N-acetylglucosamine					331:351	O-linked β-N-acetylglucosamine	322:351	O-linked β-N-acetylglucosamine	322:351	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	1	60	theme	demanding	156:164	arg1	maturation					109:118	Meiotic maturation	101:118	Meiotic maturation	101:118	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	1	60	theme	demanding	156:164	arg1	processes					166:174	metabolically demanding processes	142:174	metabolically demanding processes	142:174	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	1	60	theme	demanding	156:164	arg1	fertilization					124:136	fertilization	124:136	fertilization	124:136	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	1	61	theme	nutrient	243:250	arg1	availability					252:263	nutrient availability	243:263	nutrient availability	243:263	Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability.
30793403	5	62	theme	oocyte	863:868	arg1	COCs					881:884	COCs	881:884	COCs	881:884	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	5	62	theme	oocyte	863:868	arg1	complexes					870:878	bovine cumulus oocyte complexes	848:878	bovine cumulus oocyte complexes (COCs)	848:885	OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites.
30793403	6	63	theme	meiotic	1122:1128	arg1	spindles					1130:1137	the meiotic spindles	1118:1137	the meiotic spindles	1118:1137	O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles.
30793403	2	64	theme	posttranslational	371:387	arg1	modification					389:400	a posttranslational modification	369:400	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.	266:494	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	64	theme	posttranslational	371:387	arg1	function					467:474	the function	463:474	the function of oocyte proteins	463:493	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	64	theme	posttranslational	371:387	arg1	sensor					435:440	a cellular nutrient sensor	415:440	a cellular nutrient sensor	415:440	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	10	65	theme	zygote	1558:1563	arg1	development					1565:1575	zygote development	1558:1575	zygote development	1558:1575	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	8	66	theme	bovine	1303:1308	arg1	COCs					1310:1313	bovine COCs	1303:1313	bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor	1303:1369	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	10	67	from	effects	1674:1680	arg1	formation					1746:1754	pronuclear formation	1735:1754	pronuclear formation	1735:1754	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	10	67	from	effects	1674:1680	arg1	decondensation					1715:1728	sperm head decondensation	1704:1728	sperm head decondensation	1704:1728	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	10	67	from	effects	1674:1680	arg1	penetration					1691:1701	sperm penetration	1685:1701	sperm penetration	1685:1701	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30793403	2	68	theme	cellular	417:424	arg1	modification					389:400	a posttranslational modification	369:400	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.	266:494	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	68	theme	cellular	417:424	arg1	function					467:474	the function	463:474	the function of oocyte proteins	463:493	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	2	68	theme	cellular	417:424	arg1	sensor					435:440	a cellular nutrient sensor	415:440	a cellular nutrient sensor	415:440	O-GlcNAcylation-the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins-is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins.
30793403	8	69	theme	O-GlcNAc	1257:1264	arg1	cycling					1266:1272	O-GlcNAc cycling	1257:1272	O-GlcNAc cycling	1257:1272	To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor.
30793403	7	70	theme	expression	1146:1155	arg1	patterns					1157:1164	These expression patterns	1140:1164	These expression patterns	1140:1164	These expression patterns were evolutionarily conserved in human oocytes.
30793403	0	71	theme	O-GlcNAc	14:21	arg1	homeostasis					23:33	O-GlcNAc homeostasis	14:33	O-GlcNAc homeostasis	14:33	Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization.
30793403	10	72	theme	pronuclear	1735:1744	arg1	formation					1746:1754	pronuclear formation	1735:1754	pronuclear formation	1735:1754	However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation.
30905461	6	0	theme	different	745:753	arg1	types					755:759	64 different types	742:759	64 different types of diseases	742:771	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	10	1	theme	molecular	1589:1597	arg1	mechanisms					1599:1608	the molecular mechanisms	1585:1608	the molecular mechanisms behind these observations	1585:1634	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	7	2	theme	diseases	974:981	arg1	types					944:948	55 different types	931:948	55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis	931:1082	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	3	theme	healthy	1317:1323	arg1	controls					1325:1332	healthy controls	1317:1332	healthy controls	1317:1332	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	9	4	theme	SA	1509:1510	arg1	levels					1512:1517	serum SA levels	1503:1517	serum SA levels	1503:1517	Thus, the regulations of serum SA levels were much more complicated than previously assumed.
30905461	7	5	theme	serum	1281:1285	arg1	levels					1290:1295	median serum SA levels	1274:1295	median serum SA levels	1274:1295	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	5	6	theme	diseases	596:603	arg1	types					581:585	different types	571:585	different types of human diseases	571:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	6	7	with	individuals	712:722	arg1	types					755:759	64 different types	742:759	64 different types of diseases	742:771	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	7	8	theme	different	934:942	arg1	types					944:948	55 different types	931:948	55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis	931:1082	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	10	9	theme	SA	1653:1654	arg1	biomarker					1665:1673	serum SA a useful biomarker	1647:1673	serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases	1647:1761	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	1	10	theme	O-linked	189:196	arg1	glycans					198:204	O-linked glycans	189:204	O-linked glycans	189:204	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	6	11	with	patients	728:735	arg1	types					755:759	64 different types	742:759	64 different types of diseases	742:771	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	1	12	gly	glycoproteins	134:146	arg1	Most					86:89	Most	86:89	Most	86:89	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	1	12	gly	glycoproteins	134:146	arg1	proteins					94:101	proteins	94:101	proteins in human blood circulation	94:128	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	1	12	gly	glycoproteins	134:146	arg1	glycoproteins					134:146	glycoproteins	134:146	glycoproteins with one or more covalently linked N- or O-linked glycans	134:204	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	1	13	theme	blood	112:116	arg1	circulation					118:128	human blood circulation	106:128	human blood circulation	106:128	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	5	14	from	comparison	534:543	arg1	types					581:585	different types	571:585	different types of human diseases	571:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	8	15	from	increase	1358:1365	arg1	SD					1380:1381	SD	1380:1381	SD	1380:1381	Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers.
30905461	8	15	from	increase	1358:1365	arg1	mean					1374:1377	mean	1374:1377	mean	1374:1377	Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers.
30905461	8	15	from	increase	1358:1365	arg1	values					1396:1401	the mean (SD) and -Log10p values	1370:1401	values	1396:1401	Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers.
30905461	5	16	theme	SA	558:559	arg1	levels					561:566	the serum SA levels	548:566	the serum SA levels in different types of human diseases	548:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	5	17	from	levels	561:566	arg1	types					581:585	different types	571:585	different types of human diseases	571:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	3	18	theme	wide	320:323	arg1	range					325:329	a wide range	318:329	a wide range of physiological and pathological processes	318:373	SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s.
30905461	1	19	link	linked	176:181	arg1	N-					183:184	one or more covalently linked N-	153:184	one or more covalently linked N-	153:184	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	4	20	theme	serum	442:446	arg1	levels					451:456	Increased serum SA levels	432:456	Increased serum SA levels	432:456	Increased serum SA levels have been associated with different types of cancers.
30905461	6	21	theme	clinical	654:661	arg1	results					672:678	160,537 clinical lab test results	646:678	160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	646:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	1	22	from	proteins	94:101	arg1	circulation					118:128	human blood circulation	106:128	human blood circulation	106:128	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	8	23	theme	-Log10p	1388:1394	arg1	values					1396:1401	the mean (SD) and -Log10p values	1370:1401	values	1396:1401	Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers.
30905461	6	24	theme	current	631:637	arg1	study					639:643	current study	631:643	current study	631:643	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	7	25	theme	rheumatoid	1026:1035	arg1	arthritis					1037:1045	rheumatoid arthritis	1026:1045	rheumatoid arthritis	1026:1045	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	5	26	from	types	581:585	arg1	comparison					534:543	a systematic comparison	521:543	a systematic comparison of the serum SA levels in different types of human diseases	521:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	6	27	from	individuals	712:722	arg1	levels					692:697	serum SA levels	683:697	serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	683:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	6	27	from	individuals	712:722	arg1	results					672:678	160,537 clinical lab test results	646:678	160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	646:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	0	28	theme	SA	10:11	arg1	levels					13:18	The serum SA levels	0:18	The serum SA levels	0:18	The serum SA levels are significantly increased in sepsis but decreased in cirrhosis.
30905461	6	29	from	patients	728:735	arg1	levels					692:697	serum SA levels	683:697	serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	683:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	6	29	from	patients	728:735	arg1	results					672:678	160,537 clinical lab test results	646:678	160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	646:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	3	30	theme	processes	365:373	arg1	range					325:329	a wide range	318:329	a wide range of physiological and pathological processes	318:373	SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s.
30905461	10	31	theme	personalized	1689:1700	arg1	diagnosis					1702:1710	personalized diagnosis	1689:1710	personalized diagnosis	1689:1710	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	6	32	theme	past	784:787	arg1	years					791:795	the past 5 years	780:795	the past 5 years in our hospital	780:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	7	33	theme	SA	1148:1149	arg1	levels					1151:1156	median serum SA levels	1135:1156	median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls	1135:1332	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	10	34	theme	useful	1658:1663	arg1	biomarker					1665:1673	serum SA a useful biomarker	1647:1673	serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases	1647:1761	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	6	35	theme	SA	689:690	arg1	levels					692:697	serum SA levels	683:697	serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	683:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	7	36	theme	median	1135:1140	arg1	levels					1151:1156	median serum SA levels	1135:1156	median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls	1135:1332	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	6	37	theme	test	667:670	arg1	results					672:678	160,537 clinical lab test results	646:678	160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	646:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	7	38	theme	cancer	953:958	arg1	types					944:948	55 different types	931:948	55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis	931:1082	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	2	39	theme	terminal	248:255	arg1	monosaccharide					257:270	the terminal monosaccharide	244:270	the terminal monosaccharide on the glycans	244:285	Sialic acid (SA) generally occurs as the terminal monosaccharide on the glycans.
30905461	2	40	theme	Sialic	207:212	arg1	SA					220:221	SA	220:221	SA	220:221	Sialic acid (SA) generally occurs as the terminal monosaccharide on the glycans.
30905461	2	40	theme	Sialic	207:212	arg1	acid					214:217	Sialic acid	207:217	Sialic acid (SA)	207:222	Sialic acid (SA) generally occurs as the terminal monosaccharide on the glycans.
30905461	7	41	theme	noncancer	964:972	arg1	sepsis					991:996	sepsis	991:996	sepsis	991:996	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	41	theme	noncancer	964:972	arg1	arthritis					1037:1045	rheumatoid arthritis	1026:1045	rheumatoid arthritis	1026:1045	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	41	theme	noncancer	964:972	arg1	encephalitis					1071:1082	encephalitis	1071:1082	encephalitis	1071:1082	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	41	theme	noncancer	964:972	arg1	pancreatitis					999:1010	pancreatitis	999:1010	pancreatitis	999:1010	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	41	theme	noncancer	964:972	arg1	diseases					974:981	noncancer diseases	964:981	noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis	964:1082	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	41	theme	noncancer	964:972	arg1	cancer					1018:1023	bone cancer	1013:1023	bone cancer	1013:1023	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	41	theme	noncancer	964:972	arg1	cancer					1059:1064	pancreatic cancer	1048:1064	pancreatic cancer	1048:1064	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	9	42	theme	serum	1503:1507	arg1	levels					1512:1517	serum SA levels	1503:1517	serum SA levels	1503:1517	Thus, the regulations of serum SA levels were much more complicated than previously assumed.
30905461	6	43	from	years	791:795	arg1	hospital					804:811	our hospital	800:811	our hospital	800:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	5	44	theme	human	590:594	arg1	diseases					596:603	human diseases	590:603	human diseases	590:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	9	45	theme	levels	1512:1517	arg1	regulations					1488:1498	the regulations	1484:1498	the regulations of serum SA levels	1484:1517	Thus, the regulations of serum SA levels were much more complicated than previously assumed.
30905461	9	45	theme	levels	1512:1517	arg1	complicated					1534:1544	complicated	1534:1544	complicated	1534:1544	Thus, the regulations of serum SA levels were much more complicated than previously assumed.
30905461	7	46	theme	SA	1287:1288	arg1	levels					1290:1295	median serum SA levels	1274:1295	median serum SA levels	1274:1295	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	1	47	theme	linked	176:181	arg1	N-					183:184	one or more covalently linked N-	153:184	one or more covalently linked N-	153:184	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	7	48	theme	median	1274:1279	arg1	levels					1290:1295	median serum SA levels	1274:1295	median serum SA levels	1274:1295	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	10	49	theme	a	1656:1656	arg1	biomarker					1665:1673	serum SA a useful biomarker	1647:1673	serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases	1647:1761	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	4	50	theme	Increased	432:440	arg1	levels					451:456	Increased serum SA levels	432:456	Increased serum SA levels	432:456	Increased serum SA levels have been associated with different types of cancers.
30905461	4	51	theme	cancers	503:509	arg1	types					494:498	different types	484:498	different types of cancers	484:509	Increased serum SA levels have been associated with different types of cancers.
30905461	10	52	theme	serum	1647:1651	arg1	biomarker					1665:1673	serum SA a useful biomarker	1647:1673	serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases	1647:1761	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	3	53	from	SA	288:289	arg1	glycoproteins					294:306	glycoproteins	294:306	glycoproteins	294:306	SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s.
30905461	5	54	theme	systematic	523:532	arg1	comparison					534:543	a systematic comparison	521:543	a systematic comparison of the serum SA levels in different types of human diseases	521:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	1	55	theme	human	106:110	arg1	circulation					118:128	human blood circulation	106:128	human blood circulation	106:128	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	8	56	theme	greatest	1349:1356	arg1	increase					1358:1365	the greatest increase	1345:1365	the greatest increase in the mean (SD) and -Log10p values	1345:1401	Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers.
30905461	7	57	theme	-Log10p	881:887	arg1	values					890:895	p (-Log10p) values	878:895	p (-Log10p) values	878:895	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	57	theme	-Log10p	881:887	arg1	mean					855:858	the mean	851:858	the mean (SD)	851:863	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	58	theme	renal	1220:1224	arg1	cyst					1226:1229	renal cyst	1220:1229	renal cyst	1220:1229	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	1	59	with	glycoproteins	134:146	arg1	N-					183:184	one or more covalently linked N-	153:184	one or more covalently linked N-	153:184	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	1	59	with	glycoproteins	134:146	arg1	glycans					198:204	O-linked glycans	189:204	O-linked glycans	189:204	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	7	60	theme	p	878:878	arg1	values					890:895	p (-Log10p) values	878:895	p (-Log10p) values	878:895	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	60	theme	p	878:878	arg1	mean					855:858	the mean	851:858	the mean (SD)	851:863	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	2	61	from	monosaccharide	257:270	arg1	glycans					279:285	the glycans	275:285	the glycans	275:285	Sialic acid (SA) generally occurs as the terminal monosaccharide on the glycans.
30905461	4	62	theme	different	484:492	arg1	types					494:498	different types	484:498	different types of cancers	484:509	Increased serum SA levels have been associated with different types of cancers.
30905461	1	63	link	O-linked	189:196	arg1	glycans					198:204	O-linked glycans	189:204	O-linked glycans	189:204	Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans.
30905461	5	64	theme	levels	561:566	arg1	comparison					534:543	a systematic comparison	521:543	a systematic comparison of the serum SA levels in different types of human diseases	521:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	7	65	dep	increased	1125:1133	arg1	p<0.05					1103:1108	p<0.05	1103:1108	p<0.05	1103:1108	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	4	66	theme	SA	448:449	arg1	levels					451:456	Increased serum SA levels	432:456	Increased serum SA levels	432:456	Increased serum SA levels have been associated with different types of cancers.
30905461	6	67	theme	lab	663:665	arg1	results					672:678	160,537 clinical lab test results	646:678	160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	646:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	7	68	theme	pancreatic	1048:1057	arg1	cancer					1059:1064	pancreatic cancer	1048:1064	pancreatic cancer	1048:1064	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	5	69	theme	different	571:579	arg1	types					581:585	different types	571:585	different types of human diseases	571:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	0	70	theme	serum	4:8	arg1	levels					13:18	The serum SA levels	0:18	The serum SA levels	0:18	The serum SA levels are significantly increased in sepsis but decreased in cirrhosis.
30905461	7	71	dep	p<0.05	1103:1108	arg1	-Log10p>1.30					1111:1122	-Log10p>1.30	1111:1122	-Log10p>1.30	1111:1122	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	7	72	theme	hepatic	1185:1191	arg1	encephalopathy					1193:1206	hepatic encephalopathy	1185:1206	hepatic encephalopathy	1185:1206	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	3	73	theme	pathological	352:363	arg1	processes					365:373	physiological and pathological processes	334:373	physiological and pathological processes	334:373	SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s.
30905461	5	74	theme	serum	552:556	arg1	levels					561:566	the serum SA levels	548:566	the serum SA levels in different types of human diseases	548:603	However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported.
30905461	3	75	theme	physiological	334:346	arg1	processes					365:373	physiological and pathological processes	334:373	physiological and pathological processes	334:373	SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s.
30905461	10	76	with	patients	1730:1737	arg1	diseases					1754:1761	different diseases	1744:1761	different diseases	1744:1761	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	7	77	theme	bone	1013:1016	arg1	cancer					1018:1023	bone cancer	1013:1023	bone cancer	1013:1023	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	6	78	theme	healthy	704:710	arg1	individuals					712:722	healthy individuals	704:722	healthy individuals	704:722	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	3	79	gly	glycoproteins	294:306	arg1	glycoproteins					294:306	glycoproteins	294:306	glycoproteins	294:306	SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s.
30905461	7	80	theme	serum	1142:1146	arg1	levels					1151:1156	median serum SA levels	1135:1156	median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls	1135:1332	Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls.
30905461	10	81	theme	different	1744:1752	arg1	diseases					1754:1761	different diseases	1744:1761	different diseases	1744:1761	Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
30905461	6	82	theme	levels	692:697	arg1	results					672:678	160,537 clinical lab test results	646:678	160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	646:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	8	83	located	observed	1407:1414	arg1	sepsis					1419:1424	sepsis	1419:1424	sepsis	1419:1424	Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers.
30905461	8	83	located	observed	1407:1414	arg2	increase					1358:1365	the greatest increase	1345:1365	the greatest increase in the mean (SD) and -Log10p values	1345:1401	Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers.
30905461	6	84	theme	serum	683:687	arg1	levels					692:697	serum SA levels	683:697	serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital	683:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	6	85	theme	diseases	764:771	arg1	types					755:759	64 different types	742:759	64 different types of diseases	742:771	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	6	86	from	results	672:678	arg1	patients					728:735	patients	728:735	patients with 64 different types of diseases during the past 5 years in our hospital	728:811	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30905461	6	86	from	results	672:678	arg1	individuals					712:722	healthy individuals	704:722	healthy individuals	704:722	In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed.
30287368	5	0	theme	potent	1097:1102	arg1	effects					1115:1121	potent inhibitory effects	1097:1121	potent inhibitory effects	1097:1121	Furthermore, PIP-1 showed potent inhibitory effects on growth of HT-29 and MCF-7 cells.
30287368	4	1	dep	scavenge	982:989	arg1	scavenge					1017:1024	scavenge	1017:1024	scavenge DPPH radials	1017:1037	Pharmacological results revealed that PIP-1 could effectively scavenge hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
30287368	4	1	dep	scavenge	982:989	arg1	chelate					1043:1049	chelate	1043:1049	chelate ferrous metal ions	1043:1068	Pharmacological results revealed that PIP-1 could effectively scavenge hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
30287368	0	2	theme	polysaccharide	94:107	arg1	bioactivities					53:65	bioactivities	53:65	bioactivities	53:65	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	0	2	theme	polysaccharide	94:107	arg1	analysis					16:23	Physicochemical analysis	0:23	Physicochemical analysis	0:23	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	0	2	theme	polysaccharide	94:107	arg1	elucidation					37:47	structural elucidation	26:47	structural elucidation	26:47	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	0	3	from	analysis	16:23	arg1	mycelia					134:140	Phellinus igniarius mycelia	114:140	Phellinus igniarius mycelia	114:140	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	1	4	theme	medicinal	190:198	arg1	fungus					200:205	a well-known edible and medicinal fungus	166:205	a well-known edible and medicinal fungus consumed in Asia for centuries	166:236	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	1	4	theme	medicinal	190:198	arg1	igniarius					153:161	Phellinus igniarius	143:161	Phellinus igniarius	143:161	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	3	5	theme	main	829:832	arg1	chain					834:838	the main chain	825:838	the main chain according to the GC-MS and NMR results	825:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	6	theme	side	799:802	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	6	theme	side	799:802	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	6	theme	side	799:802	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	6	theme	side	799:802	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	0	7	theme	igniarius	124:132	arg1	mycelia					134:140	Phellinus igniarius mycelia	114:140	Phellinus igniarius mycelia	114:140	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	3	8	contain	had	554:556	arg2	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	8	contain	had	554:556	arg1	PIP-1					548:552	PIP-1	548:552	PIP-1	548:552	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	8	contain	had	554:556	arg2	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	8	contain	had	554:556	arg2	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	8	contain	had	554:556	arg2	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	6	9	theme	glycosidic	1269:1278	arg1	bond					1280:1283	only α-type glycosidic bond	1257:1283	only α-type glycosidic bond	1257:1283	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	2	10	theme	Phellinus	308:316	arg1	mycelia					328:334	Phellinus igniarius mycelia	308:334	Phellinus igniarius mycelia	308:334	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	3	11	theme	high	585:588	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	11	theme	high	585:588	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	11	theme	high	585:588	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	11	theme	high	585:588	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	12	theme	single	771:776	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	12	theme	single	771:776	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	12	theme	single	771:776	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	12	theme	single	771:776	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	0	13	theme	Phellinus	114:122	arg1	mycelia					134:140	Phellinus igniarius mycelia	114:140	Phellinus igniarius mycelia	114:140	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	6	14	theme	α-type	1262:1267	arg1	bond					1280:1283	only α-type glycosidic bond	1257:1283	only α-type glycosidic bond	1257:1283	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	6	15	theme	human	1347:1351	arg1	health					1353:1358	human health	1347:1358	human health	1347:1358	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	0	16	from	bioactivities	53:65	arg1	mycelia					134:140	Phellinus igniarius mycelia	114:140	Phellinus igniarius mycelia	114:140	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	3	17	theme	high	560:563	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	17	theme	high	560:563	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	17	theme	high	560:563	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	17	theme	high	560:563	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	18	theme	NMR	867:869	arg1	results					871:877	the GC-MS and NMR results	853:877	results	871:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	19	theme	molecular	565:573	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	19	theme	molecular	565:573	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	19	theme	molecular	565:573	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	19	theme	molecular	565:573	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	2	20	theme	antioxidant	475:485	arg1	activities					501:510	its antioxidant and antitumor activities	471:510	its antioxidant and antitumor activities	471:510	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	0	21	from	elucidation	37:47	arg1	mycelia					134:140	Phellinus igniarius mycelia	114:140	Phellinus igniarius mycelia	114:140	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	3	22	theme	intrinsic	590:598	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	22	theme	intrinsic	590:598	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	22	theme	intrinsic	590:598	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	22	theme	intrinsic	590:598	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	23	theme	GC-MS	857:861	arg1	results					871:877	the GC-MS and NMR results	853:877	results	871:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	0	24	theme	Physicochemical	0:14	arg1	analysis					16:23	Physicochemical analysis	0:23	Physicochemical analysis	0:23	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	6	25	theme	helical	1235:1241	arg1	structure					1243:1251	triple helical structure	1228:1251	triple helical structure	1228:1251	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	4	26	theme	hydroxyl	991:998	arg1	radicals					1000:1007	hydroxyl radicals	991:1007	hydroxyl radicals	991:1007	Pharmacological results revealed that PIP-1 could effectively scavenge hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
30287368	5	27	theme	inhibitory	1104:1113	arg1	effects					1115:1121	potent inhibitory effects	1097:1121	potent inhibitory effects	1097:1121	Furthermore, PIP-1 showed potent inhibitory effects on growth of HT-29 and MCF-7 cells.
30287368	0	28	theme	structural	26:35	arg1	elucidation					37:47	structural elucidation	26:47	structural elucidation	26:47	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	5	29	theme	MCF-7	1146:1150	arg1	cells					1152:1156	HT-29 and MCF-7 cells	1136:1156	cells	1152:1156	Furthermore, PIP-1 showed potent inhibitory effects on growth of HT-29 and MCF-7 cells.
30287368	6	30	theme	high-molecular-weight	1189:1209	arg1	PIP-1					1211:1215	high-molecular-weight PIP-1	1189:1215	high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond	1189:1283	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	6	31	theme	triple	1228:1233	arg1	structure					1243:1251	triple helical structure	1228:1251	triple helical structure	1228:1251	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	2	32	theme	product	458:464	arg1	analysis					428:435	analysis	428:435	analysis of its depolymerized product	428:464	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	5	33	theme	cells	1152:1156	arg1	growth					1126:1131	growth	1126:1131	growth of HT-29 and MCF-7 cells	1126:1156	Furthermore, PIP-1 showed potent inhibitory effects on growth of HT-29 and MCF-7 cells.
30287368	2	34	theme	igniarius	318:326	arg1	mycelia					328:334	Phellinus igniarius mycelia	308:334	Phellinus igniarius mycelia	308:334	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	6	35	contain	containing	1217:1226	arg1	PIP-1					1211:1215	high-molecular-weight PIP-1	1189:1215	high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond	1189:1283	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	6	35	contain	containing	1217:1226	arg2	bond					1280:1283	only α-type glycosidic bond	1257:1283	only α-type glycosidic bond	1257:1283	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	6	35	contain	containing	1217:1226	arg2	structure					1243:1251	triple helical structure	1228:1251	triple helical structure	1228:1251	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	2	36	theme	depolymerized	444:456	arg1	product					458:464	its depolymerized product	440:464	its depolymerized product	440:464	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	3	37	theme	linear	616:621	arg1	backbone					633:640	a linear repeating backbone	614:640	a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose	614:709	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	4	38	theme	metal	1059:1063	arg1	ions					1065:1068	ferrous metal ions	1051:1068	ferrous metal ions	1051:1068	Pharmacological results revealed that PIP-1 could effectively scavenge hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
30287368	3	39	theme	repeating	623:631	arg1	backbone					633:640	a linear repeating backbone	614:640	a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose	614:709	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	5	40	theme	HT-29	1136:1140	arg1	cells					1152:1156	HT-29 and MCF-7 cells	1136:1156	cells	1152:1156	Furthermore, PIP-1 showed potent inhibitory effects on growth of HT-29 and MCF-7 cells.
30287368	2	41	theme	antitumor	491:499	arg1	activities					501:510	its antioxidant and antitumor activities	471:510	its antioxidant and antitumor activities	471:510	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	3	42	theme	1 → 6	750:754	arg1	linkages					757:764	α-(1 → 6) linkages	747:764	α-(1 → 6) linkages	747:764	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	6	43	theme	functional	1308:1317	arg1	promise					1291:1297	promise	1291:1297	promise	1291:1297	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	6	43	theme	functional	1308:1317	arg1	foods					1319:1323	novel functional foods	1302:1323	novel functional foods	1302:1323	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	2	44	theme	present	246:252	arg1	study					254:258	the present study	242:258	the present study	242:258	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	1	45	theme	Phellinus	143:151	arg1	fungus					200:205	a well-known edible and medicinal fungus	166:205	a well-known edible and medicinal fungus consumed in Asia for centuries	166:236	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	1	45	theme	Phellinus	143:151	arg1	igniarius					153:161	Phellinus igniarius	143:161	Phellinus igniarius	143:161	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	2	46	theme	detailed	389:396	arg1	structures					398:407	its detailed structures	385:407	its detailed structures	385:407	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	6	47	theme	novel	1302:1306	arg1	promise					1291:1297	promise	1291:1297	promise	1291:1297	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	6	47	theme	novel	1302:1306	arg1	foods					1319:1323	novel functional foods	1302:1323	novel functional foods	1302:1323	These findings suggested that high-molecular-weight PIP-1 containing triple helical structure and only α-type glycosidic bond holds promise as novel functional foods and agents to promote human health.
30287368	3	48	link	6-O-linked	811:820	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	48	link	6-O-linked	811:820	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	48	link	6-O-linked	811:820	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	48	link	6-O-linked	811:820	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	49	theme	triple	894:899	arg1	structure					909:917	triple helical structure	894:917	triple helical structure	894:917	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	4	50	theme	ferrous	1051:1057	arg1	ions					1065:1068	ferrous metal ions	1051:1068	ferrous metal ions	1051:1068	Pharmacological results revealed that PIP-1 could effectively scavenge hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
30287368	3	51	theme	α-	747:748	arg1	linkages					757:764	α-(1 → 6) linkages	747:764	α-(1 → 6) linkages	747:764	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	0	52	from	mycelia	134:140	arg1	polysaccharide					94:107	a high-molecular-weight polysaccharide	70:107	a high-molecular-weight polysaccharide from Phellinus igniarius mycelia	70:140	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	0	52	from	mycelia	134:140	arg1	bioactivities					53:65	bioactivities	53:65	bioactivities	53:65	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	0	52	from	mycelia	134:140	arg1	analysis					16:23	Physicochemical analysis	0:23	Physicochemical analysis	0:23	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	0	52	from	mycelia	134:140	arg1	elucidation					37:47	structural elucidation	26:47	structural elucidation	26:47	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	3	53	theme	helical	901:907	arg1	structure					909:917	triple helical structure	894:917	triple helical structure	894:917	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	2	54	theme	physicochemical	341:355	arg1	properties					357:366	its physicochemical properties	337:366	its physicochemical properties	337:366	In the present study, a polysaccharide named PIP-1 was obtained from Phellinus igniarius mycelia, its physicochemical properties were determined, its detailed structures were elucidated by analysis of its depolymerized product, and its antioxidant and antitumor activities were evaluated.
30287368	0	55	theme	high-molecular-weight	72:92	arg1	polysaccharide					94:107	a high-molecular-weight polysaccharide	70:107	a high-molecular-weight polysaccharide from Phellinus igniarius mycelia	70:140	Physicochemical analysis, structural elucidation and bioactivities of a high-molecular-weight polysaccharide from Phellinus igniarius mycelia.
30287368	1	56	theme	well-known	168:177	arg1	fungus					200:205	a well-known edible and medicinal fungus	166:205	a well-known edible and medicinal fungus consumed in Asia for centuries	166:236	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	1	56	theme	well-known	168:177	arg1	igniarius					153:161	Phellinus igniarius	143:161	Phellinus igniarius	143:161	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	3	57	theme	6-O-linked	811:820	arg1	weight					575:580	a high molecular weight	558:580	a high molecular weight	558:580	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	57	theme	6-O-linked	811:820	arg1	α‑terminal‑D‑Glcp					778:794	single α‑terminal‑D‑Glcp	771:794	single α‑terminal‑D‑Glcp	771:794	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	57	theme	6-O-linked	811:820	arg1	chains					804:809	side chains	799:809	side chains 6-O-linked to the main chain according to the GC-MS and NMR results	799:877	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	3	57	theme	6-O-linked	811:820	arg1	viscosity					600:608	a high intrinsic viscosity	583:608	a high intrinsic viscosity	583:608	Results showed that PIP-1 had a high molecular weight, a high intrinsic viscosity and a linear repeating backbone composed of glucopyranose (Glcp), galactopyranose, and mannopyranose joined by α-(1 → 4), α-(1 → 3), and α-(1 → 6) linkages, and single α‑terminal‑D‑Glcp as side chains 6-O-linked to the main chain according to the GC-MS and NMR results, and exhibited triple helical structure.
30287368	4	58	theme	Pharmacological	920:934	arg1	results					936:942	Pharmacological results	920:942	Pharmacological results	920:942	Pharmacological results revealed that PIP-1 could effectively scavenge hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
30287368	1	59	theme	edible	179:184	arg1	fungus					200:205	a well-known edible and medicinal fungus	166:205	a well-known edible and medicinal fungus consumed in Asia for centuries	166:236	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	1	59	theme	edible	179:184	arg1	igniarius					153:161	Phellinus igniarius	143:161	Phellinus igniarius	143:161	Phellinus igniarius is a well-known edible and medicinal fungus consumed in Asia for centuries.
30287368	4	60	theme	DPPH	1026:1029	arg1	radials					1031:1037	DPPH radials	1026:1037	DPPH radials	1026:1037	Pharmacological results revealed that PIP-1 could effectively scavenge hydroxyl radicals, partly scavenge DPPH radials and chelate ferrous metal ions.
29524020	11	0	theme	metabolism	1569:1578	arg1	dysregulation					1580:1592	metabolism dysregulation	1569:1592	metabolism dysregulation associated to obesity or cancer	1569:1624	Thus, a crosstalk exists between O-GlcNAcylation and mTOR signaling in contexts of metabolism dysregulation associated to obesity or cancer.
29524020	1	1	theme	acids	142:146	arg1	metabolisms					164:174	glucose, amino acids, fatty acids and nucleotides metabolisms	114:174	glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	114:241	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	4	2	theme	OGT	625:627	arg1	expression					629:638	OGT expression	625:638	OGT expression	625:638	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
29524020	3	3	theme	O-GlcNAc	355:362	arg1	transferase					364:374	O-GlcNAc transferase	355:374	O-GlcNAc transferase (OGT)	355:380	O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins.
29524020	3	3	theme	O-GlcNAc	355:362	arg1	enzyme					389:394	the enzyme	385:394	the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins	385:474	O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins.
29524020	3	3	theme	O-GlcNAc	355:362	arg1	OGT					377:379	OGT	377:379	OGT	377:379	O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins.
29524020	9	4	theme	OGT	1319:1321	arg1	levels					1343:1348	OGT and O-GlcNAcylation levels	1319:1348	OGT and O-GlcNAcylation levels in both normal and colon cancer cells	1319:1386	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	11	5	theme	dysregulation	1580:1592	arg1	contexts					1557:1564	contexts	1557:1564	contexts of metabolism dysregulation associated to obesity or cancer	1557:1624	Thus, a crosstalk exists between O-GlcNAcylation and mTOR signaling in contexts of metabolism dysregulation associated to obesity or cancer.
29524020	8	6	theme	cancer	1189:1194	arg1	cells					1196:1200	colon cancer cells	1183:1200	colon cancer cells	1183:1200	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	5	7	theme	increased	711:719	arg1	activation					721:730	an increased activation	708:730	an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway	708:799	Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway.
29524020	6	8	theme	cancer	873:878	arg1	cells					880:884	cancer cells	873:884	cancer cells	873:884	Other works demonstrate that mTOR regulates protein O-GlcNAcylation in cancer cells through stabilization of OGT.
29524020	2	9	theme	β-N-acetylglucosaminylation	298:324	arg1	processes					344:352	O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes	289:352	O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes	289:352	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	8	10	theme	colon	1183:1187	arg1	cells					1196:1200	colon cancer cells	1183:1200	colon cancer cells	1183:1200	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	9	11	theme	O-GlcNAcylation	1327:1341	arg1	levels					1343:1348	OGT and O-GlcNAcylation levels	1319:1348	OGT and O-GlcNAcylation levels in both normal and colon cancer cells	1319:1386	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	2	12	theme	O-linked	289:296	arg1	O-GlcNAcylation					327:341	O-GlcNAcylation	327:341	O-GlcNAcylation	327:341	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	2	12	theme	O-linked	289:296	arg1	β-N-acetylglucosaminylation					298:324	O-linked β-N-acetylglucosaminylation	289:324	O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes	289:352	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	11	13	dep	O-GlcNAcylation	1519:1533	arg1	signaling					1544:1552	signaling	1544:1552	signaling	1544:1552	Thus, a crosstalk exists between O-GlcNAcylation and mTOR signaling in contexts of metabolism dysregulation associated to obesity or cancer.
29524020	1	14	theme	hexosamine	65:74	arg1	HBP					98:100	HBP	98:100	HBP	98:100	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	1	14	theme	hexosamine	65:74	arg1	pathway					89:95	The hexosamine biosynthetic pathway	61:95	The hexosamine biosynthetic pathway (HBP)	61:101	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	4	15	theme	expression	629:638	arg1	increase					613:620	an increase	610:620	an increase of OGT expression and global O-GlcNAcylation levels	610:672	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
29524020	7	16	theme	obese	1006:1010	arg1	mice					1012:1015	obese mice	1006:1015	obese mice predisposed to diabetes	1006:1039	In this context, we studied the cross-talk between these two metabolic sensors in vivo in obese mice predisposed to diabetes and in vitro in normal and colon cancer cells.
29524020	1	17	theme	biosynthetic	76:87	arg1	HBP					98:100	HBP	98:100	HBP	98:100	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	1	17	theme	biosynthetic	76:87	arg1	pathway					89:95	The hexosamine biosynthetic pathway	61:95	The hexosamine biosynthetic pathway (HBP)	61:101	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	1	18	theme	nucleotides	152:162	arg1	metabolisms					164:174	glucose, amino acids, fatty acids and nucleotides metabolisms	114:174	glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	114:241	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	5	19	theme	pathway	793:799	arg1	target					766:771	the nutrient sensing mammalian target	735:771	the nutrient sensing mammalian target of rapamycin (mTOR) pathway	735:799	Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway.
29524020	6	20	theme	protein	846:852	arg1	O-GlcNAcylation					854:868	protein O-GlcNAcylation	846:868	protein O-GlcNAcylation in cancer cells	846:884	Other works demonstrate that mTOR regulates protein O-GlcNAcylation in cancer cells through stabilization of OGT.
29524020	7	21	dep	normal	1057:1062	arg1	cells					1081:1085	cells	1081:1085	cells	1081:1085	In this context, we studied the cross-talk between these two metabolic sensors in vivo in obese mice predisposed to diabetes and in vitro in normal and colon cancer cells.
29524020	6	22	from	O-GlcNAcylation	854:868	arg1	cells					880:884	cancer cells	873:884	cancer cells	873:884	Other works demonstrate that mTOR regulates protein O-GlcNAcylation in cancer cells through stabilization of OGT.
29524020	4	23	theme	glucose	516:522	arg1	metabolism					524:533	glucose metabolism	516:533	glucose metabolism	516:533	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
29524020	9	24	with	treatments	1278:1287	arg1	regulators					1299:1308	mTOR regulators	1294:1308	mTOR regulators	1294:1308	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	0	25	theme	Cross	0:4	arg1	regulation					6:15	Cross regulation	0:15	Cross regulation between mTOR signaling and O-GlcNAcylation.	0:59	Cross regulation between mTOR signaling and O-GlcNAcylation.
29524020	7	26	theme	metabolic	977:985	arg1	sensors					987:993	these two metabolic sensors	967:993	these two metabolic sensors	967:993	In this context, we studied the cross-talk between these two metabolic sensors in vivo in obese mice predisposed to diabetes and in vitro in normal and colon cancer cells.
29524020	1	27	theme	uridine	180:186	arg1	N-acetylglucosamine					200:218	uridine diphosphate N-acetylglucosamine	180:218	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	180:241	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	1	27	theme	uridine	180:186	arg1	UDP-GlcNAc					221:230	UDP-GlcNAc	221:230	UDP-GlcNAc	221:230	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	0	28	theme	mTOR	25:28	arg1	signaling					30:38	mTOR signaling	25:38	mTOR signaling	25:38	Cross regulation between mTOR signaling and O-GlcNAcylation.
29524020	10	29	theme	signaling	1443:1451	arg1	activation					1453:1462	mTOR signaling activation	1438:1462	mTOR signaling activation	1438:1462	However, deregulation of O-GlcNAcylation affects mTOR signaling activation only in cancer cells.
29524020	5	30	theme	mammalian	756:764	arg1	target					766:771	the nutrient sensing mammalian target	735:771	the nutrient sensing mammalian target of rapamycin (mTOR) pathway	735:799	Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway.
29524020	10	31	theme	mTOR	1438:1441	arg1	activation					1453:1462	mTOR signaling activation	1438:1462	mTOR signaling activation	1438:1462	However, deregulation of O-GlcNAcylation affects mTOR signaling activation only in cancer cells.
29524020	1	32	theme	diphosphate	188:198	arg1	N-acetylglucosamine					200:218	uridine diphosphate N-acetylglucosamine	180:218	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	180:241	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	1	32	theme	diphosphate	188:198	arg1	UDP-GlcNAc					221:230	UDP-GlcNAc	221:230	UDP-GlcNAc	221:230	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	9	33	from	levels	1343:1348	arg1	normal					1358:1363	normal	1358:1363	normal	1358:1363	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	9	33	from	levels	1343:1348	arg1	cancer					1375:1380	colon cancer	1369:1380	colon cancer	1369:1380	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	9	34	theme	colon	1369:1373	arg1	cancer					1375:1380	colon cancer	1369:1380	colon cancer	1369:1380	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	5	35	theme	target	766:771	arg1	activation					721:730	an increased activation	708:730	an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway	708:799	Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway.
29524020	4	36	theme	Several	477:483	arg1	studies					485:491	Several studies	477:491	Several studies	477:491	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
29524020	1	37	theme	N-acetylglucosamine	200:218	arg1	synthesis					233:241	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	180:241	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	180:241	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	3	38	theme	O-GlcNAc	437:444	arg1	residue					447:453	the N-acetylglucosamine (O-GlcNAc) residue	412:453	the N-acetylglucosamine (O-GlcNAc) residue onto target proteins	412:474	O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins.
29524020	2	39	link	O-linked	289:296	arg1	O-GlcNAcylation					327:341	O-GlcNAcylation	327:341	O-GlcNAcylation	327:341	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	2	39	link	O-linked	289:296	arg1	β-N-acetylglucosaminylation					298:324	O-linked β-N-acetylglucosaminylation	289:324	O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes	289:352	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	8	40	theme	O-GlcNAcylation	1121:1135	arg1	levels					1103:1108	levels	1103:1108	levels of OGT and O-GlcNAcylation	1103:1135	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	8	41	from	tissues	1171:1177	arg1	mice					1160:1163	obese mice	1154:1163	obese mice	1154:1163	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	3	42	theme	target	460:465	arg1	proteins					467:474	target proteins	460:474	target proteins	460:474	O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins.
29524020	5	43	theme	rapamycin	776:784	arg1	pathway					793:799	rapamycin (mTOR) pathway	776:799	rapamycin (mTOR) pathway	776:799	Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway.
29524020	3	44	theme	N-acetylglucosamine	416:434	arg1	residue					447:453	the N-acetylglucosamine (O-GlcNAc) residue	412:453	the N-acetylglucosamine (O-GlcNAc) residue onto target proteins	412:474	O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins.
29524020	8	45	theme	higher	1228:1233	arg1	activation					1235:1244	a higher activation	1226:1244	a higher activation of mTOR signaling	1226:1262	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	7	46	theme	colon	1068:1072	arg1	cancer					1074:1079	colon cancer	1068:1079	colon cancer	1068:1079	In this context, we studied the cross-talk between these two metabolic sensors in vivo in obese mice predisposed to diabetes and in vitro in normal and colon cancer cells.
29524020	1	47	theme	glucose	114:120	arg1	metabolisms					164:174	glucose, amino acids, fatty acids and nucleotides metabolisms	114:174	glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	114:241	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	8	48	theme	OGT	1113:1115	arg1	levels					1103:1108	levels	1103:1108	levels of OGT and O-GlcNAcylation	1103:1135	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	6	49	theme	OGT	911:913	arg1	stabilization					894:906	stabilization	894:906	stabilization of OGT	894:913	Other works demonstrate that mTOR regulates protein O-GlcNAcylation in cancer cells through stabilization of OGT.
29524020	6	50	theme	Other	802:806	arg1	works					808:812	Other works	802:812	Other works	802:812	Other works demonstrate that mTOR regulates protein O-GlcNAcylation in cancer cells through stabilization of OGT.
29524020	10	51	theme	cancer	1472:1477	arg1	cells					1479:1483	cancer cells	1472:1483	cancer cells	1472:1483	However, deregulation of O-GlcNAcylation affects mTOR signaling activation only in cancer cells.
29524020	9	52	dep	normal	1358:1363	arg1	cells					1382:1386	cells	1382:1386	cells	1382:1386	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	4	53	dep	dysregulations	535:548	arg1	associated					550:559	associated	550:559	dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels	535:672	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
29524020	5	54	theme	nutrient	739:746	arg1	target					766:771	the nutrient sensing mammalian target	735:771	the nutrient sensing mammalian target of rapamycin (mTOR) pathway	735:799	Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway.
29524020	8	55	from	cells	1196:1200	arg1	mice					1160:1163	obese mice	1154:1163	obese mice	1154:1163	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	2	56	theme	sugar	273:277	arg1	donor					279:283	the nucleotide sugar donor	258:283	the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes	258:352	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	2	56	theme	sugar	273:277	arg1	UDP-GlcNAc					244:253	UDP-GlcNAc	244:253	UDP-GlcNAc	244:253	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	10	57	theme	O-GlcNAcylation	1414:1428	arg1	deregulation					1398:1409	deregulation	1398:1409	deregulation of O-GlcNAcylation	1398:1428	However, deregulation of O-GlcNAcylation affects mTOR signaling activation only in cancer cells.
29524020	1	58	theme	amino	123:127	arg1	acids					129:133	amino acids	123:133	amino acids	123:133	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	4	59	theme	O-GlcNAcylation	651:665	arg1	levels					667:672	global O-GlcNAcylation levels	644:672	global O-GlcNAcylation levels	644:672	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
29524020	5	60	theme	sensing	748:754	arg1	target					766:771	the nutrient sensing mammalian target	735:771	the nutrient sensing mammalian target of rapamycin (mTOR) pathway	735:799	Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway.
29524020	2	61	theme	nucleotide	262:271	arg1	donor					279:283	the nucleotide sugar donor	258:283	the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes	258:352	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	2	61	theme	nucleotide	262:271	arg1	UDP-GlcNAc					244:253	UDP-GlcNAc	244:253	UDP-GlcNAc	244:253	UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes.
29524020	8	62	theme	obese	1154:1158	arg1	mice					1160:1163	obese mice	1154:1163	obese mice	1154:1163	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	1	63	theme	acids	129:133	arg1	metabolisms					164:174	glucose, amino acids, fatty acids and nucleotides metabolisms	114:174	glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis	114:241	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	4	64	theme	global	644:649	arg1	levels					667:672	global O-GlcNAcylation levels	644:672	global O-GlcNAcylation levels	644:672	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
29524020	8	65	theme	colon	1165:1169	arg1	tissues					1171:1177	colon tissues	1165:1177	colon tissues	1165:1177	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	9	66	theme	mTOR	1294:1297	arg1	regulators					1299:1308	mTOR regulators	1294:1308	mTOR regulators	1294:1308	In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells.
29524020	8	67	theme	signaling	1254:1262	arg1	activation					1235:1244	a higher activation	1226:1244	a higher activation of mTOR signaling	1226:1262	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	8	68	theme	mTOR	1249:1252	arg1	signaling					1254:1262	mTOR signaling	1249:1262	mTOR signaling	1249:1262	We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling.
29524020	1	69	theme	fatty	136:140	arg1	acids					142:146	fatty acids	136:146	fatty acids	136:146	The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis.
29524020	4	70	theme	levels	667:672	arg1	increase					613:620	an increase	610:620	an increase of OGT expression and global O-GlcNAcylation levels	610:672	Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels.
31326749	1	0	theme	NGLY1	124:128	arg1	disorder					161:168	a rare inherited disorder	144:168	a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins	144:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	1	0	theme	NGLY1	124:128	arg1	deficiency					130:139	NGLY1 deficiency	124:139	NGLY1 deficiency	124:139	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	2	1	theme	cell	315:318	arg1	line					327:330	An induced pluripotent stem cell (iPSC) line	287:330	An induced pluripotent stem cell (iPSC) line	287:330	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	3	2	theme	iPSC	471:474	arg1	model					476:480	Our iPSC model	467:480	Our iPSC model	467:480	Our iPSC model offers a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients.
31326749	2	3	theme	NGLY1	455:459	arg1	gene					461:464	the NGLY1 gene	451:464	the NGLY1 gene	451:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	2	4	from	mutation	415:422	arg1	gene					461:464	the NGLY1 gene	451:464	the NGLY1 gene	451:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	0	5	theme	p.R401X	88:94	arg1	mutation					96:103	a homozygous p.R401X mutation	75:103	a homozygous p.R401X mutation in the NGLY1 gene	75:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	0	6	theme	homozygous	77:86	arg1	mutation					96:103	a homozygous p.R401X mutation	75:103	a homozygous p.R401X mutation in the NGLY1 gene	75:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	3	7	theme	useful	491:496	arg1	resource					498:505	a useful resource	489:505	a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients	489:602	Our iPSC model offers a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients.
31326749	1	8	theme	rare	146:149	arg1	disorder					161:168	a rare inherited disorder	144:168	a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins	144:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	1	8	theme	rare	146:149	arg1	deficiency					130:139	NGLY1 deficiency	124:139	NGLY1 deficiency	124:139	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	2	9	theme	patient	391:397	arg1	fibroblasts					362:372	the dermal fibroblasts	351:372	the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene	351:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	1	10	theme	inherited	151:159	arg1	disorder					161:168	a rare inherited disorder	144:168	a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins	144:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	1	10	theme	inherited	151:159	arg1	deficiency					130:139	NGLY1 deficiency	124:139	NGLY1 deficiency	124:139	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	0	11	theme	stem	23:26	arg1	line					33:36	pluripotent stem cell line	11:36	pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene	11:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	0	11	theme	stem	23:26	arg1	TRNDi010-C					39:48	TRNDi010-C	39:48	TRNDi010-C	39:48	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	0	12	theme	pluripotent	11:21	arg1	line					33:36	pluripotent stem cell line	11:36	pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene	11:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	0	12	theme	pluripotent	11:21	arg1	TRNDi010-C					39:48	TRNDi010-C	39:48	TRNDi010-C	39:48	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	1	13	link	N-linked	255:262	arg1	proteins					277:284	N-linked glycosylated proteins	255:284	N-linked glycosylated proteins	255:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	0	14	from	patient	58:64	arg1	line					33:36	pluripotent stem cell line	11:36	pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene	11:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	0	14	from	patient	58:64	arg1	TRNDi010-C					39:48	TRNDi010-C	39:48	TRNDi010-C	39:48	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	3	15	dep	resource	498:505	arg1	study					510:514	study	510:514	to study the disease pathophysiology	507:542	Our iPSC model offers a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients.
31326749	3	15	dep	resource	498:505	arg1	develop					551:557	develop	551:557	to develop therapeutics for treatment of NGLY1 patients	548:602	Our iPSC model offers a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients.
31326749	2	16	theme	p.R401X	427:433	arg1	mutation					415:422	homozygous mutation	404:422	homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene	404:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	0	17	theme	NGLY1	112:116	arg1	gene					118:121	the NGLY1 gene	108:121	the NGLY1 gene	108:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	2	18	theme	dermal	355:360	arg1	fibroblasts					362:372	the dermal fibroblasts	351:372	the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene	351:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	0	19	theme	cell	28:31	arg1	line					33:36	pluripotent stem cell line	11:36	pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene	11:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	0	19	theme	cell	28:31	arg1	TRNDi010-C					39:48	TRNDi010-C	39:48	TRNDi010-C	39:48	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	1	20	theme	N-linked	255:262	arg1	proteins					277:284	N-linked glycosylated proteins	255:284	N-linked glycosylated proteins	255:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	2	21	theme	16-year-old	379:389	arg1	patient					391:397	a 16-year-old patient	377:397	a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene	377:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	1	22	theme	glycosylated	264:275	arg1	proteins					277:284	N-linked glycosylated proteins	255:284	N-linked glycosylated proteins	255:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	1	23	from	mutations	180:188	arg1	gene					203:206	the NGLY1 gene	193:206	the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins	193:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	2	24	theme	stem	310:313	arg1	iPSC					321:324	iPSC	321:324	iPSC	321:324	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	2	24	theme	stem	310:313	arg1	cell					315:318	pluripotent stem cell	298:318	An induced pluripotent stem cell (iPSC) line	287:330	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	2	25	theme	homozygous	404:413	arg1	mutation					415:422	homozygous mutation	404:422	homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene	404:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	0	26	contain	carrying	66:73	arg2	mutation					96:103	a homozygous p.R401X mutation	75:103	a homozygous p.R401X mutation in the NGLY1 gene	75:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	0	26	contain	carrying	66:73	arg1	patient					58:64	a patient	56:64	a patient carrying a homozygous p.R401X mutation in the NGLY1 gene	56:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31326749	2	27	theme	pluripotent	298:308	arg1	iPSC					321:324	iPSC	321:324	iPSC	321:324	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	2	27	theme	pluripotent	298:308	arg1	cell					315:318	pluripotent stem cell	298:318	An induced pluripotent stem cell (iPSC) line	287:330	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	3	28	theme	disease	520:526	arg1	pathophysiology					528:542	the disease pathophysiology	516:542	the disease pathophysiology	516:542	Our iPSC model offers a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients.
31326749	2	29	with	patient	391:397	arg1	mutation					415:422	homozygous mutation	404:422	homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene	404:464	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	2	30	theme	induced	290:296	arg1	line					327:330	An induced pluripotent stem cell (iPSC) line	287:330	An induced pluripotent stem cell (iPSC) line	287:330	An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 16-year-old patient with homozygous mutation of p.R401X (c.1201 A>T) in the NGLY1 gene.
31326749	3	31	theme	NGLY1	589:593	arg1	patients					595:602	NGLY1 patients	589:602	NGLY1 patients	589:602	Our iPSC model offers a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients.
31326749	1	32	gly	glycosylated	264:275	arg1	proteins					277:284	N-linked glycosylated proteins	255:284	N-linked glycosylated proteins	255:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	3	33	theme	patients	595:602	arg1	treatment					576:584	treatment	576:584	treatment of NGLY1 patients	576:602	Our iPSC model offers a useful resource to study the disease pathophysiology and to develop therapeutics for treatment of NGLY1 patients.
31326749	1	34	theme	NGLY1	197:201	arg1	gene					203:206	the NGLY1 gene	193:206	the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins	193:284	NGLY1 deficiency is a rare inherited disorder caused by mutations in the NGLY1 gene encoding N-glycanase 1 that is a hydrolase for N-linked glycosylated proteins.
31326749	0	35	from	mutation	96:103	arg1	gene					118:121	the NGLY1 gene	108:121	the NGLY1 gene	108:121	An induced pluripotent stem cell line (TRNDi010-C) from a patient carrying a homozygous p.R401X mutation in the NGLY1 gene.
31164895	7	0	theme	Ovary	1172:1176	arg1	mutant					1189:1194	the Chinese Hamster Ovary (CHO)-gmt5 mutant	1152:1194	the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity	1152:1251	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	7	1	theme	Chinese	1156:1162	arg1	CHO					1179:1181	CHO	1179:1181	CHO	1179:1181	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	7	1	theme	Chinese	1156:1162	arg1	Ovary					1172:1176	Chinese Hamster Ovary	1156:1176	the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity	1152:1251	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	10	2	theme	-fucosylation	1759:1771	arg1	increase					1737:1744	a significant increase	1723:1744	a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins	1723:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	4	3	link	plant-derived	726:738	arg1	biopharmaceuticals					740:757	plant-derived biopharmaceuticals	726:757	plant-derived biopharmaceuticals	726:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	4	4	theme	α	693:693	arg1	present					715:721	the α(1,3)-fucose epitope present	689:721	the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals	689:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	7	5	dep	P.	1079:1080	arg1	tricornutum					1082:1092	tricornutum	1082:1092	tricornutum	1082:1092	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	7	6	theme	endogenous	1208:1217	arg1	activity					1244:1251	its endogenous GDP-L-fucose transporter activity	1204:1251	its endogenous GDP-L-fucose transporter activity	1204:1251	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	5	7	gly	fucosylation	864:875	arg1	glycoproteins					884:896	the glycoproteins	880:896	the glycoproteins in P. tricornutum	880:914	In this paper, we have studied molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum.
31164895	4	8	theme	1,3	695:697	arg1	present					715:721	the α(1,3)-fucose epitope present	689:721	the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals	689:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	10	9	theme	endogenous	1787:1796	arg1	glycoproteins					1798:1810	the diatom endogenous glycoproteins	1776:1810	the diatom endogenous glycoproteins	1776:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	1	10	theme	plant	217:221	arg1	farming					233:239	plant molecular farming	217:239	plant molecular farming for the production of high-value molecules such as monoclonal antibodies	217:312	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	4	11	theme	potential	661:669	arg1	immunogenicity					671:684	the potential immunogenicity	657:684	the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals	657:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	4	11	theme	potential	661:669	arg1	Meanwhile					646:654	Meanwhile	646:654	Meanwhile	646:654	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	7	12	theme	coding	1119:1124	arg1	sequence					1126:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	7	13	theme	-gmt5	1183:1187	arg1	mutant					1189:1194	the Chinese Hamster Ovary (CHO)-gmt5 mutant	1152:1194	the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity	1152:1251	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	6	14	theme	putative	970:977	arg1	transporter					1007:1017	a putative P. tricornutum GDP-L-fucose transporter	968:1017	a putative P. tricornutum GDP-L-fucose transporter	968:1017	Based on sequence similarities, we have identified a putative P. tricornutum GDP-L-fucose transporter and three fucosyltransferase (FuT) candidates.
31164895	3	15	gly	glycoproteins	613:625	arg1	glycoproteins					613:625	endogenous glycoproteins	602:625	endogenous glycoproteins	602:625	Indeed, such epitope has previously been found on N-glycans of endogenous glycoproteins in P. tricornutum.
31164895	7	16	theme	GDP-L-fucose	1094:1105	arg1	sequence					1126:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	4	17	theme	plant-derived	726:738	arg1	biopharmaceuticals					740:757	plant-derived biopharmaceuticals	726:757	plant-derived biopharmaceuticals	726:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	7	18	theme	P.	1079:1080	arg1	sequence					1126:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	3	19	theme	glycoproteins	613:625	arg1	N-glycans					589:597	N-glycans	589:597	N-glycans of endogenous glycoproteins in P. tricornutum	589:643	Indeed, such epitope has previously been found on N-glycans of endogenous glycoproteins in P. tricornutum.
31164895	8	20	gly	rescue	1309:1314	arg1	line					1374:1377	this CHO-gmt5 mutant cell line	1348:1377	this CHO-gmt5 mutant cell line	1348:1377	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	5	21	from	glycoproteins	884:896	arg1	tricornutum					904:914	P. tricornutum	901:914	P. tricornutum	901:914	In this paper, we have studied molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum.
31164895	9	22	theme	candidates	1540:1549	arg1	candidates					1540:1549	the three FuT candidates	1526:1549	the three FuT candidates	1526:1549	In addition, we overexpressed one of the three FuT candidates, namely the FuT54599, in P. tricornutum and investigated its localization within Golgi stacks of the diatom.
31164895	9	22	theme	candidates	1540:1549	arg1	one					1519:1521	one	1519:1521	one	1519:1521	In addition, we overexpressed one of the three FuT candidates, namely the FuT54599, in P. tricornutum and investigated its localization within Golgi stacks of the diatom.
31164895	9	22	theme	candidates	1540:1549	arg1	FuT54599					1563:1570	the FuT54599	1559:1570	namely the FuT54599	1552:1570	In addition, we overexpressed one of the three FuT candidates, namely the FuT54599, in P. tricornutum and investigated its localization within Golgi stacks of the diatom.
31164895	8	23	theme	CHO-gmt5	1353:1360	arg1	line					1374:1377	this CHO-gmt5 mutant cell line	1348:1377	this CHO-gmt5 mutant cell line	1348:1377	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	8	24	gly	fucosylation	1320:1331	arg1	proteins					1336:1343	proteins	1336:1343	proteins	1336:1343	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	4	25	theme	present	715:721	arg1	immunogenicity					671:684	the potential immunogenicity	657:684	the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals	657:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	4	25	theme	present	715:721	arg1	Meanwhile					646:654	Meanwhile	646:654	Meanwhile	646:654	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	7	26	theme	transporter	1232:1242	arg1	activity					1244:1251	its endogenous GDP-L-fucose transporter activity	1204:1251	its endogenous GDP-L-fucose transporter activity	1204:1251	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	0	27	gly	Fucosylation	86:97	arg1	Glycoproteins					102:114	Glycoproteins	102:114	Glycoproteins	102:114	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	2	28	from	protein	496:502	arg1	tricornutum					510:520	P. tricornutum	507:520	P. tricornutum	507:520	For example, incorporation of fucose residues in the glycans N-linked to protein in P. tricornutum is questionable.
31164895	2	29	link	N-linked	484:491	arg1	glycans					476:482	the glycans	472:482	the glycans N-linked to protein in P. tricornutum	472:520	For example, incorporation of fucose residues in the glycans N-linked to protein in P. tricornutum is questionable.
31164895	8	30	theme	functional	1403:1412	arg1	activity					1414:1421	the functional activity	1399:1421	the functional activity of the diatom transporter	1399:1447	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	5	31	theme	molecular	819:827	arg1	actors					829:834	molecular actors	819:834	molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum	819:914	In this paper, we have studied molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum.
31164895	2	32	theme	fucose	453:458	arg1	residues					460:467	fucose residues	453:467	fucose residues	453:467	For example, incorporation of fucose residues in the glycans N-linked to protein in P. tricornutum is questionable.
31164895	4	33	theme	-fucose	699:705	arg1	present					715:721	the α(1,3)-fucose epitope present	689:721	the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals	689:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	8	34	theme	diatom	1430:1435	arg1	transporter					1437:1447	the diatom transporter	1426:1447	the diatom transporter	1426:1447	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	8	35	theme	tricornutum	1274:1284	arg1	transporter					1286:1296	the P. tricornutum transporter	1267:1296	the P. tricornutum transporter	1267:1296	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	8	35	theme	tricornutum	1274:1284	arg1	able					1301:1304	able	1301:1304	able	1301:1304	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	10	36	gly	-fucosylation	1759:1771	arg1	glycoproteins					1798:1810	the diatom endogenous glycoproteins	1776:1810	the diatom endogenous glycoproteins	1776:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	0	37	theme	Transporter	33:43	arg1	Characterization					0:15	Characterization	0:15	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.	0:155	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	9	38	theme	Golgi	1632:1636	arg1	stacks					1638:1643	Golgi stacks	1632:1643	Golgi stacks of the diatom	1632:1657	In addition, we overexpressed one of the three FuT candidates, namely the FuT54599, in P. tricornutum and investigated its localization within Golgi stacks of the diatom.
31164895	1	39	theme	key	347:349	arg1	metabolism					356:365	key cell metabolism	347:365	key cell metabolism occurring in this diatom such as protein glycosylation	347:420	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	8	40	theme	appropriate	1457:1467	arg1	localization					1475:1486	its appropriate Golgi localization	1453:1486	its appropriate Golgi localization	1453:1486	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	4	41	from	biopharmaceuticals	740:757	arg1	immunogenicity					671:684	the potential immunogenicity	657:684	the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals	657:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	4	41	from	biopharmaceuticals	740:757	arg1	Meanwhile					646:654	Meanwhile	646:654	Meanwhile	646:654	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	10	42	theme	1,3	1755:1757	arg1	-fucosylation					1759:1771	the α(1,3)-fucosylation	1749:1771	the α(1,3)-fucosylation of the diatom endogenous glycoproteins	1749:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	9	43	theme	diatom	1652:1657	arg1	stacks					1638:1643	Golgi stacks	1632:1643	Golgi stacks of the diatom	1632:1657	In addition, we overexpressed one of the three FuT candidates, namely the FuT54599, in P. tricornutum and investigated its localization within Golgi stacks of the diatom.
31164895	2	44	from	incorporation	436:448	arg1	glycans					476:482	the glycans	472:482	the glycans N-linked to protein in P. tricornutum	472:520	For example, incorporation of fucose residues in the glycans N-linked to protein in P. tricornutum is questionable.
31164895	1	45	theme	high-value	263:272	arg1	molecules					274:282	high-value molecules	263:282	high-value molecules such as monoclonal antibodies	263:312	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	1	45	theme	high-value	263:272	arg1	antibodies					303:312	monoclonal antibodies	292:312	monoclonal antibodies	292:312	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	7	46	theme	Hamster	1164:1170	arg1	CHO					1179:1181	CHO	1179:1181	CHO	1179:1181	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	7	46	theme	Hamster	1164:1170	arg1	Ovary					1172:1176	Chinese Hamster Ovary	1156:1176	the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity	1152:1251	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	6	47	theme	sequence	926:933	arg1	similarities					935:946	sequence similarities	926:946	sequence similarities	926:946	Based on sequence similarities, we have identified a putative P. tricornutum GDP-L-fucose transporter and three fucosyltransferase (FuT) candidates.
31164895	1	48	theme	monoclonal	292:301	arg1	antibodies					303:312	monoclonal antibodies	292:312	monoclonal antibodies	292:312	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	5	49	gly	glycoproteins	884:896	arg1	glycoproteins					884:896	the glycoproteins	880:896	the glycoproteins in P. tricornutum	880:914	In this paper, we have studied molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum.
31164895	8	50	theme	cell	1369:1372	arg1	line					1374:1377	this CHO-gmt5 mutant cell line	1348:1377	this CHO-gmt5 mutant cell line	1348:1377	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	8	51	theme	P.	1271:1272	arg1	transporter					1286:1296	the P. tricornutum transporter	1267:1296	the P. tricornutum transporter	1267:1296	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	8	51	theme	P.	1271:1272	arg1	able					1301:1304	able	1301:1304	able	1301:1304	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	10	52	theme	glycoproteins	1798:1810	arg1	-fucosylation					1759:1771	the α(1,3)-fucosylation	1749:1771	the α(1,3)-fucosylation of the diatom endogenous glycoproteins	1749:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	3	53	located	found	580:584	arg2	epitope					552:558	such epitope	547:558	such epitope	547:558	Indeed, such epitope has previously been found on N-glycans of endogenous glycoproteins in P. tricornutum.
31164895	3	53	located	found	580:584	arg1	N-glycans					589:597	N-glycans	589:597	N-glycans of endogenous glycoproteins in P. tricornutum	589:643	Indeed, such epitope has previously been found on N-glycans of endogenous glycoproteins in P. tricornutum.
31164895	5	54	theme	glycoproteins	884:896	arg1	fucosylation					864:875	the fucosylation	860:875	the fucosylation of the glycoproteins in P. tricornutum	860:914	In this paper, we have studied molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum.
31164895	6	55	theme	GDP-L-fucose	994:1005	arg1	transporter					1007:1017	a putative P. tricornutum GDP-L-fucose transporter	968:1017	a putative P. tricornutum GDP-L-fucose transporter	968:1017	Based on sequence similarities, we have identified a putative P. tricornutum GDP-L-fucose transporter and three fucosyltransferase (FuT) candidates.
31164895	0	56	theme	Phaeodactylum	130:142	arg1	tricornutum					144:154	the Diatom Phaeodactylum tricornutum	119:154	the Diatom Phaeodactylum tricornutum	119:154	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	10	57	theme	diatom	1780:1785	arg1	glycoproteins					1798:1810	the diatom endogenous glycoproteins	1776:1810	the diatom endogenous glycoproteins	1776:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	4	58	from	immunogenicity	671:684	arg1	biopharmaceuticals					740:757	plant-derived biopharmaceuticals	726:757	plant-derived biopharmaceuticals	726:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	1	59	theme	molecular	223:231	arg1	farming					233:239	plant molecular farming	217:239	plant molecular farming for the production of high-value molecules such as monoclonal antibodies	217:312	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	6	60	theme	P.	979:980	arg1	transporter					1007:1017	a putative P. tricornutum GDP-L-fucose transporter	968:1017	a putative P. tricornutum GDP-L-fucose transporter	968:1017	Based on sequence similarities, we have identified a putative P. tricornutum GDP-L-fucose transporter and three fucosyltransferase (FuT) candidates.
31164895	0	61	from	Fucosylation	86:97	arg1	tricornutum					144:154	the Diatom Phaeodactylum tricornutum	119:154	the Diatom Phaeodactylum tricornutum	119:154	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	8	62	theme	mutant	1362:1367	arg1	line					1374:1377	this CHO-gmt5 mutant cell line	1348:1377	this CHO-gmt5 mutant cell line	1348:1377	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	7	63	theme	putative	1070:1077	arg1	sequence					1126:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	3	64	theme	endogenous	602:611	arg1	glycoproteins					613:625	endogenous glycoproteins	602:625	endogenous glycoproteins	602:625	Indeed, such epitope has previously been found on N-glycans of endogenous glycoproteins in P. tricornutum.
31164895	5	65	from	fucosylation	864:875	arg1	tricornutum					904:914	P. tricornutum	901:914	P. tricornutum	901:914	In this paper, we have studied molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum.
31164895	7	66	theme	transporter	1107:1117	arg1	sequence					1126:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence	1066:1133	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	6	67	dep	P.	979:980	arg1	tricornutum					982:992	tricornutum	982:992	tricornutum	982:992	Based on sequence similarities, we have identified a putative P. tricornutum GDP-L-fucose transporter and three fucosyltransferase (FuT) candidates.
31164895	9	68	theme	FuT	1536:1538	arg1	candidates					1540:1549	the three FuT candidates	1526:1549	the three FuT candidates	1526:1549	In addition, we overexpressed one of the three FuT candidates, namely the FuT54599, in P. tricornutum and investigated its localization within Golgi stacks of the diatom.
31164895	8	69	theme	proteins	1336:1343	arg1	fucosylation					1320:1331	the fucosylation	1316:1331	the fucosylation of proteins	1316:1343	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	3	70	from	N-glycans	589:597	arg1	tricornutum					633:643	P. tricornutum	630:643	P. tricornutum	630:643	Indeed, such epitope has previously been found on N-glycans of endogenous glycoproteins in P. tricornutum.
31164895	6	71	theme	FuT	1049:1051	arg1	candidates					1054:1063	three fucosyltransferase (FuT) candidates	1023:1063	three fucosyltransferase (FuT) candidates	1023:1063	Based on sequence similarities, we have identified a putative P. tricornutum GDP-L-fucose transporter and three fucosyltransferase (FuT) candidates.
31164895	6	72	theme	fucosyltransferase	1029:1046	arg1	candidates					1054:1063	three fucosyltransferase (FuT) candidates	1023:1063	three fucosyltransferase (FuT) candidates	1023:1063	Based on sequence similarities, we have identified a putative P. tricornutum GDP-L-fucose transporter and three fucosyltransferase (FuT) candidates.
31164895	0	73	theme	Diatom	123:128	arg1	tricornutum					144:154	the Diatom Phaeodactylum tricornutum	119:154	the Diatom Phaeodactylum tricornutum	119:154	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	4	74	theme	epitope	707:713	arg1	present					715:721	the α(1,3)-fucose epitope present	689:721	the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals	689:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	0	75	theme	Glycoproteins	102:114	arg1	Fucosylation					86:97	the Fucosylation	82:97	the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum	82:154	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	4	76	theme	debate	780:785	arg1	matter					770:775	a matter	768:775	a matter of debate	768:785	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	4	76	theme	debate	780:785	arg1	Meanwhile					646:654	Meanwhile	646:654	Meanwhile	646:654	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	7	77	theme	GDP-L-fucose	1219:1230	arg1	activity					1244:1251	its endogenous GDP-L-fucose transporter activity	1204:1251	its endogenous GDP-L-fucose transporter activity	1204:1251	The putative P. tricornutum GDP-L-fucose transporter coding sequence was expressed in the Chinese Hamster Ovary (CHO)-gmt5 mutant lacking its endogenous GDP-L-fucose transporter activity.
31164895	5	78	from	tricornutum	904:914	arg1	fucosylation					864:875	the fucosylation	860:875	the fucosylation of the glycoproteins in P. tricornutum	860:914	In this paper, we have studied molecular actors potentially involved in the fucosylation of the glycoproteins in P. tricornutum.
31164895	1	79	theme	protein	400:406	arg1	glycosylation					408:420	protein glycosylation	400:420	protein glycosylation	400:420	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	0	80	theme	GDP-Fucose	22:31	arg1	Transporter					33:43	a GDP-Fucose Transporter	20:43	a GDP-Fucose Transporter	20:43	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	10	81	gly	glycoproteins	1798:1810	arg1	glycoproteins					1798:1810	the diatom endogenous glycoproteins	1776:1810	the diatom endogenous glycoproteins	1776:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	2	82	theme	residues	460:467	arg1	incorporation					436:448	incorporation	436:448	incorporation of fucose residues in the glycans N-linked to protein in P. tricornutum	436:520	For example, incorporation of fucose residues in the glycans N-linked to protein in P. tricornutum is questionable.
31164895	10	83	theme	FuT54599	1705:1712	arg1	overexpression					1683:1696	overexpression	1683:1696	overexpression of the FuT54599	1683:1712	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	0	84	theme	Fucosyltransferase	51:68	arg1	Characterization					0:15	Characterization	0:15	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.	0:155	Characterization of a GDP-Fucose Transporter and a Fucosyltransferase Involved in the Fucosylation of Glycoproteins in the Diatom Phaeodactylum tricornutum.
31164895	2	85	theme	N-linked	484:491	arg1	glycans					476:482	the glycans	472:482	the glycans N-linked to protein in P. tricornutum	472:520	For example, incorporation of fucose residues in the glycans N-linked to protein in P. tricornutum is questionable.
31164895	8	86	theme	transporter	1437:1447	arg1	activity					1414:1421	the functional activity	1399:1421	the functional activity of the diatom transporter	1399:1447	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	8	86	theme	transporter	1437:1447	arg1	localization					1475:1486	its appropriate Golgi localization	1453:1486	its appropriate Golgi localization	1453:1486	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	10	87	theme	significant	1725:1735	arg1	increase					1737:1744	a significant increase	1723:1744	a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins	1723:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	1	88	theme	cell	351:354	arg1	metabolism					356:365	key cell metabolism	347:365	key cell metabolism occurring in this diatom such as protein glycosylation	347:420	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31164895	10	89	theme	α	1753:1753	arg1	-fucosylation					1759:1771	the α(1,3)-fucosylation	1749:1771	the α(1,3)-fucosylation of the diatom endogenous glycoproteins	1749:1810	Our findings show that overexpression of the FuT54599 leads to a significant increase of the α(1,3)-fucosylation of the diatom endogenous glycoproteins.
31164895	8	90	theme	Golgi	1469:1473	arg1	localization					1475:1486	its appropriate Golgi localization	1453:1486	its appropriate Golgi localization	1453:1486	We show that the P. tricornutum transporter is able to rescue the fucosylation of proteins in this CHO-gmt5 mutant cell line, thus demonstrating the functional activity of the diatom transporter and its appropriate Golgi localization.
31164895	3	91	theme	such	547:550	arg1	epitope					552:558	such epitope	547:558	such epitope	547:558	Indeed, such epitope has previously been found on N-glycans of endogenous glycoproteins in P. tricornutum.
31164895	4	92	from	present	715:721	arg1	biopharmaceuticals					740:757	plant-derived biopharmaceuticals	726:757	plant-derived biopharmaceuticals	726:757	Meanwhile, the potential immunogenicity of the α(1,3)-fucose epitope present on plant-derived biopharmaceuticals is still a matter of debate.
31164895	1	93	theme	molecules	274:282	arg1	production					249:258	the production	245:258	the production of high-value molecules such as monoclonal antibodies	245:312	Although Phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation.
31001516	1	0	theme	intersystem	313:323	arg1	crossing					325:332	efficient reverse intersystem crossing	295:332	efficient reverse intersystem crossing	295:332	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	9	1	theme	shortest	1606:1613	arg1	lifetime					1623:1630	shortest delayed lifetime	1606:1630	shortest delayed lifetime of <100 ns	1606:1641	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	6	2	theme	electroluminescent	937:954	arg1	performance					956:966	the electroluminescent performance	933:966	the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime	933:1022	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	6	2	theme	electroluminescent	937:954	arg1	dependent					1028:1036	dependent	1028:1036	dependent	1028:1036	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	8	3	theme	HOMO/LUMO	1264:1272	arg1	offsets					1274:1280	large HOMO/LUMO offsets	1258:1280	large HOMO/LUMO offsets of 1.09-1.34 eV	1258:1296	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	4	4	theme	energy	740:745	arg1	-6.14/-2.80					759:769	-6.14/-2.80	759:769	-6.14/-2.80	759:769	The HOMO/LUMO energy levels were -6.14/-2.80 for 24iPBIOXD and -6.17/-2.95 eV for iTPBIOXD.
31001516	4	4	theme	energy	740:745	arg1	levels					747:752	The HOMO/LUMO energy levels	726:752	The HOMO/LUMO energy levels	726:752	The HOMO/LUMO energy levels were -6.14/-2.80 for 24iPBIOXD and -6.17/-2.95 eV for iTPBIOXD.
31001516	1	5	theme	low	235:237	arg1	voltages					247:254	the low driving voltages	231:254	the low driving voltages	231:254	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	8	6	theme	eV	1295:1296	arg1	offsets					1274:1280	large HOMO/LUMO offsets	1258:1280	large HOMO/LUMO offsets of 1.09-1.34 eV	1258:1296	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	7	7	theme	delayed	1125:1131	arg1	lifetime					1133:1140	The delayed lifetime	1121:1140	The delayed lifetime from 579 to 2,045 ns	1121:1161	The delayed lifetime from 579 to 2,045 ns was achieved at driving forces close to or larger than 1 eV.
31001516	9	8	theme	moderate	1476:1483	arg1	eV					1511:1512	0.88-1.03 eV	1501:1512	0.88-1.03 eV	1501:1512	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	8	theme	moderate	1476:1483	arg1	offsets					1492:1498	moderate energy offsets	1476:1498	moderate energy offsets (0.88-1.03 eV)	1476:1513	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	8	9	theme	based	1233:1237	arg1	devices					1239:1245	Two TAPC based devices	1224:1245	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV	1224:1296	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	9	10	theme	inadequate	1650:1659	arg1	force					1669:1673	inadequate driving force	1650:1673	inadequate driving force of 0.47-0.75 eV for efficient exciplex formation	1650:1722	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	8	11	contain	possessing	1247:1256	arg1	devices					1239:1245	Two TAPC based devices	1224:1245	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV	1224:1296	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	8	11	contain	possessing	1247:1256	arg2	offsets					1274:1280	large HOMO/LUMO offsets	1258:1280	large HOMO/LUMO offsets of 1.09-1.34 eV	1258:1296	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	1	12	theme	small	260:264	arg1	bandgaps					282:289	small singlet-triplet bandgaps	260:289	small singlet-triplet bandgaps	260:289	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	8	13	theme	EL	1317:1318	arg1	performance					1320:1330	the best EL performance	1308:1330	the best EL performance	1308:1330	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	1	14	theme	donor/acceptor	157:170	arg1	exciplex					177:184	donor/acceptor type exciplex	157:184	donor/acceptor type exciplex	157:184	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	8	15	theme	maximum	1338:1344	arg1	EQE					1375:1377	EQE	1375:1377	EQE	1375:1377	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	8	15	theme	maximum	1338:1344	arg1	efficiency					1363:1372	maximum external quantum efficiency	1338:1372	maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor	1338:1431	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	3	16	from	nm	666:667	arg1	peak					646:649	peak	646:649	peak at 421 and 459 nm in solution, 397 and 419 nm	646:695	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	3	16	from	nm	666:667	arg1	solution					672:679	solution	672:679	solution	672:679	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	9	17	theme	EL	1519:1520	arg1	efficiency					1522:1531	EL efficiency	1519:1531	EL efficiency (~4%)	1519:1537	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	17	theme	EL	1519:1520	arg1	%					1536:1536	~4%	1534:1536	~4%	1534:1536	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	18	theme	exciplex	1705:1712	arg1	formation					1714:1722	efficient exciplex formation	1695:1722	efficient exciplex formation	1695:1722	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	8	19	theme	quantum	1355:1361	arg1	EQE					1375:1377	EQE	1375:1377	EQE	1375:1377	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	8	19	theme	quantum	1355:1361	arg1	efficiency					1363:1372	maximum external quantum efficiency	1338:1372	maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor	1338:1431	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	1	20	theme	fluorescence	407:418	arg1	OLEDs					427:431	delayed fluorescence (TADF) OLEDs	399:431	delayed fluorescence (TADF) OLEDs	399:431	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	0	21	theme	Fluorescence	127:138	arg1	OLEDs					140:144	Delayed Fluorescence OLEDs	119:144	Delayed Fluorescence OLEDs	119:144	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type Thermally Activated Delayed Fluorescence OLEDs.
31001516	4	22	dep	-6.14/-2.80	759:769	arg1	eV					801:802	eV	801:802	eV	801:802	The HOMO/LUMO energy levels were -6.14/-2.80 for 24iPBIOXD and -6.17/-2.95 eV for iTPBIOXD.
31001516	2	23	theme	N-linked	446:453	arg1	acceptors					497:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	0	24	theme	N-Benzoimidazole/Oxadiazole	0:26	arg1	Acceptors					54:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors	0:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type	0:97	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type Thermally Activated Delayed Fluorescence OLEDs.
31001516	9	25	theme	mCP	1546:1548	arg1	systems					1550:1556	mCP systems	1546:1556	mCP systems	1546:1556	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	0	26	theme	Universal	35:43	arg1	Acceptors					54:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors	0:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type	0:97	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type Thermally Activated Delayed Fluorescence OLEDs.
31001516	1	27	theme	%	348:348	arg1	excitons					350:357	100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs	345:431	100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs	345:431	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	2	28	theme	C-N	566:568	arg1	reaction					579:586	simple catalyst-free C-N coupling reaction	545:586	simple catalyst-free C-N coupling reaction	545:586	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	3	29	from	397	682:684	arg1	peak					646:649	peak	646:649	peak at 421 and 459 nm in solution, 397 and 419 nm	646:695	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	2	30	theme	hybrid	481:486	arg1	acceptors					497:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	5	31	theme	conventional	858:869	arg1	mCP					911:913	mCP	911:913	mCP	911:913	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	5	31	theme	conventional	858:869	arg1	donors					880:885	conventional electron donors	858:885	conventional electron donors such as TAPC, TCTA, and mCP	858:913	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	5	31	theme	conventional	858:869	arg1	TAPC					895:898	TAPC	895:898	TAPC	895:898	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	5	31	theme	conventional	858:869	arg1	TCTA					901:904	TCTA	901:904	TCTA	901:904	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	9	32	theme	poorest	1569:1575	arg1	performance					1580:1590	the poorest EL performance	1565:1590	the poorest EL performance (EQE <1%)	1565:1600	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	32	theme	poorest	1569:1575	arg1	%					1599:1599	EQE <1%	1593:1599	EQE <1%	1593:1599	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	6	33	theme	energy	1083:1088	arg1	offsets					1090:1096	both HOMO and LUMO energy offsets	1064:1096	offsets	1090:1096	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	2	34	theme	simple	545:550	arg1	reaction					579:586	simple catalyst-free C-N coupling reaction	545:586	simple catalyst-free C-N coupling reaction	545:586	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	7	35	from	ns	1160:1161	arg1	lifetime					1133:1140	The delayed lifetime	1121:1140	The delayed lifetime from 579 to 2,045 ns	1121:1161	The delayed lifetime from 579 to 2,045 ns was achieved at driving forces close to or larger than 1 eV.
31001516	8	36	theme	%	1409:1409	arg1	EQE					1375:1377	EQE	1375:1377	EQE	1375:1377	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	8	36	theme	%	1409:1409	arg1	efficiency					1363:1372	maximum external quantum efficiency	1338:1372	maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor	1338:1431	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	7	37	theme	driving	1179:1185	arg1	forces					1187:1192	driving forces	1179:1192	driving forces close to or larger than 1 eV	1179:1221	The delayed lifetime from 579 to 2,045 ns was achieved at driving forces close to or larger than 1 eV.
31001516	2	38	link	N-linked	446:453	arg1	acceptors					497:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	8	39	theme	iTPBIOXD	1415:1422	arg1	acceptor					1424:1431	iTPBIOXD acceptor	1415:1431	iTPBIOXD acceptor	1415:1431	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	1	40	theme	singlet-triplet	266:280	arg1	bandgaps					282:289	small singlet-triplet bandgaps	260:289	small singlet-triplet bandgaps	260:289	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	9	41	theme	EQE	1593:1595	arg1	performance					1580:1590	the poorest EL performance	1565:1590	the poorest EL performance (EQE <1%)	1565:1600	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	41	theme	EQE	1593:1595	arg1	%					1599:1599	EQE <1%	1593:1599	EQE <1%	1593:1599	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	0	42	theme	Efficient	75:83	arg1	Exciplex-Type					85:97	Highly Efficient Exciplex-Type	68:97	Highly Efficient Exciplex-Type	68:97	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type Thermally Activated Delayed Fluorescence OLEDs.
31001516	1	43	theme	reverse	305:311	arg1	crossing					325:332	efficient reverse intersystem crossing	295:332	efficient reverse intersystem crossing	295:332	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	6	44	theme	exciplex-type	972:984	arg1	OLEDs					986:990	exciplex-type OLEDs	972:990	exciplex-type OLEDs as well as the delayed lifetime	972:1022	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	9	45	theme	delayed	1615:1621	arg1	lifetime					1623:1630	shortest delayed lifetime	1606:1630	shortest delayed lifetime of <100 ns	1606:1641	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	6	46	with	dependent	1028:1036	arg1	force					1055:1059	the driving force	1043:1059	the driving force of both HOMO and LUMO energy offsets on exciplex formation	1043:1118	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	8	47	theme	large	1258:1262	arg1	offsets					1274:1280	large HOMO/LUMO offsets	1258:1280	large HOMO/LUMO offsets of 1.09-1.34 eV	1258:1296	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	7	48	dep	2,045	1154:1158	arg1	to					1151:1152	to	1151:1152	to	1151:1152	The delayed lifetime from 579 to 2,045 ns was achieved at driving forces close to or larger than 1 eV.
31001516	3	49	theme	459	662:664	arg1	nm					666:667	421 and 459 nm	654:667	nm	666:667	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	9	50	theme	ns	1640:1641	arg1	performance					1580:1590	the poorest EL performance	1565:1590	the poorest EL performance (EQE <1%)	1565:1600	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	50	theme	ns	1640:1641	arg1	lifetime					1623:1630	shortest delayed lifetime	1606:1630	shortest delayed lifetime of <100 ns	1606:1641	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	50	theme	ns	1640:1641	arg1	%					1599:1599	EQE <1%	1593:1599	EQE <1%	1593:1599	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	4	51	theme	HOMO/LUMO	730:738	arg1	-6.14/-2.80					759:769	-6.14/-2.80	759:769	-6.14/-2.80	759:769	The HOMO/LUMO energy levels were -6.14/-2.80 for 24iPBIOXD and -6.17/-2.95 eV for iTPBIOXD.
31001516	4	51	theme	HOMO/LUMO	730:738	arg1	levels					747:752	The HOMO/LUMO energy levels	726:752	The HOMO/LUMO energy levels	726:752	The HOMO/LUMO energy levels were -6.14/-2.80 for 24iPBIOXD and -6.17/-2.95 eV for iTPBIOXD.
31001516	3	52	theme	421	654:656	arg1	nm					666:667	421 and 459 nm	654:667	nm	666:667	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	1	53	theme	driving	239:245	arg1	voltages					247:254	the low driving voltages	231:254	the low driving voltages	231:254	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	9	54	theme	energy	1485:1490	arg1	eV					1511:1512	0.88-1.03 eV	1501:1512	0.88-1.03 eV	1501:1512	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	54	theme	energy	1485:1490	arg1	offsets					1492:1498	moderate energy offsets	1476:1498	moderate energy offsets (0.88-1.03 eV)	1476:1513	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	8	55	theme	TAPC	1228:1231	arg1	devices					1239:1245	Two TAPC based devices	1224:1245	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV	1224:1296	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	6	56	theme	delayed	1007:1013	arg1	lifetime					1015:1022	the delayed lifetime	1003:1022	exciplex-type OLEDs as well as the delayed lifetime	972:1022	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	9	57	theme	driving	1661:1667	arg1	force					1669:1673	inadequate driving force	1650:1673	inadequate driving force of 0.47-0.75 eV for efficient exciplex formation	1650:1722	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	8	58	theme	best	1312:1315	arg1	performance					1320:1330	the best EL performance	1308:1330	the best EL performance	1308:1330	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	1	59	theme	type	172:175	arg1	exciplex					177:184	donor/acceptor type exciplex	157:184	donor/acceptor type exciplex	157:184	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	6	60	theme	LUMO	1078:1081	arg1	offsets					1090:1096	both HOMO and LUMO energy offsets	1064:1096	offsets	1090:1096	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	9	61	theme	eV	1688:1689	arg1	force					1669:1673	inadequate driving force	1650:1673	inadequate driving force of 0.47-0.75 eV for efficient exciplex formation	1650:1722	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	6	62	theme	HOMO	1069:1072	arg1	force					1055:1059	the driving force	1043:1059	the driving force of both HOMO and LUMO energy offsets on exciplex formation	1043:1118	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	9	63	theme	efficient	1695:1703	arg1	formation					1714:1722	efficient exciplex formation	1695:1722	efficient exciplex formation	1695:1722	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	0	64	theme	Delayed	119:125	arg1	OLEDs					140:144	Delayed Fluorescence OLEDs	119:144	Delayed Fluorescence OLEDs	119:144	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type Thermally Activated Delayed Fluorescence OLEDs.
31001516	1	65	theme	delayed	399:405	arg1	OLEDs					427:431	delayed fluorescence (TADF) OLEDs	399:431	delayed fluorescence (TADF) OLEDs	399:431	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	1	66	theme	considerable	201:212	arg1	interests					214:222	considerable interests	201:222	considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing	201:332	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	2	67	theme	coupling	570:577	arg1	reaction					579:586	simple catalyst-free C-N coupling reaction	545:586	simple catalyst-free C-N coupling reaction	545:586	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	9	68	contain	containing	1443:1452	arg2	exciplex					1454:1461	exciplex	1454:1461	exciplex	1454:1461	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	68	contain	containing	1443:1452	arg1	TCTA					1438:1441	The TCTA	1434:1441	The TCTA containing exciplex	1434:1461	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	8	69	theme	external	1346:1353	arg1	EQE					1375:1377	EQE	1375:1377	EQE	1375:1377	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	8	69	theme	external	1346:1353	arg1	efficiency					1363:1372	maximum external quantum efficiency	1338:1372	maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor	1338:1431	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	6	70	theme	driving	1047:1053	arg1	force					1055:1059	the driving force	1043:1059	the driving force of both HOMO and LUMO energy offsets on exciplex formation	1043:1118	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	3	71	from	nm	694:695	arg1	peak					646:649	peak	646:649	peak at 421 and 459 nm in solution, 397 and 419 nm	646:695	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	3	71	from	nm	694:695	arg1	solution					672:679	solution	672:679	solution	672:679	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	0	72	theme	Hybrid	28:33	arg1	Acceptors					54:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors	0:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type	0:97	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type Thermally Activated Delayed Fluorescence OLEDs.
31001516	6	73	from	force	1055:1059	arg1	formation					1110:1118	exciplex formation	1101:1118	exciplex formation	1101:1118	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	0	74	theme	Electron	45:52	arg1	Acceptors					54:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors	0:62	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type	0:97	N-Benzoimidazole/Oxadiazole Hybrid Universal Electron Acceptors for Highly Efficient Exciplex-Type Thermally Activated Delayed Fluorescence OLEDs.
31001516	1	75	theme	100	345:347	arg1	%					348:348	%	348:348	%	348:348	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	6	76	theme	exciplex	1101:1108	arg1	formation					1110:1118	exciplex formation	1101:1118	exciplex formation	1101:1118	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	8	77	theme	%	1386:1386	arg1	EQE					1375:1377	EQE	1375:1377	EQE	1375:1377	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	8	77	theme	%	1386:1386	arg1	efficiency					1363:1372	maximum external quantum efficiency	1338:1372	maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor	1338:1431	Two TAPC based devices possessing large HOMO/LUMO offsets of 1.09-1.34 eV exhibited the best EL performance, with maximum external quantum efficiency (EQE) of 9.3% for 24iPBIOXD and 7.0% for iTPBIOXD acceptor.
31001516	2	78	theme	electron	488:495	arg1	acceptors					497:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	3	79	with	emission	632:639	arg1	peak					646:649	peak	646:649	peak at 421 and 459 nm in solution, 397 and 419 nm	646:695	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	6	80	theme	offsets	1090:1096	arg1	force					1055:1059	the driving force	1043:1059	the driving force of both HOMO and LUMO energy offsets on exciplex formation	1043:1118	It is found that the electroluminescent performance for exciplex-type OLEDs as well as the delayed lifetime was dependent with the driving force of both HOMO and LUMO energy offsets on exciplex formation.
31001516	2	81	theme	catalyst-free	552:564	arg1	reaction					579:586	simple catalyst-free C-N coupling reaction	545:586	simple catalyst-free C-N coupling reaction	545:586	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	3	82	theme	film	700:703	arg1	state					705:709	film state	700:709	film state	700:709	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	2	83	theme	benzoimidazole/oxadiazole	455:479	arg1	acceptors					497:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	two N-linked benzoimidazole/oxadiazole hybrid electron acceptors	442:505	Herein, two N-linked benzoimidazole/oxadiazole hybrid electron acceptors were designed and synthesized through simple catalyst-free C-N coupling reaction.
31001516	5	84	theme	electron	871:878	arg1	mCP					911:913	mCP	911:913	mCP	911:913	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	5	84	theme	electron	871:878	arg1	donors					880:885	conventional electron donors	858:885	conventional electron donors such as TAPC, TCTA, and mCP	858:913	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	5	84	theme	electron	871:878	arg1	TAPC					895:898	TAPC	895:898	TAPC	895:898	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	5	84	theme	electron	871:878	arg1	TCTA					901:904	TCTA	901:904	TCTA	901:904	Both compounds could form exciplex with conventional electron donors such as TAPC, TCTA, and mCP.
31001516	1	85	theme	high	363:366	arg1	efficiency					368:377	high efficiency	363:377	high efficiency	363:377	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
31001516	9	86	theme	EL	1577:1578	arg1	performance					1580:1590	the poorest EL performance	1565:1590	the poorest EL performance (EQE <1%)	1565:1600	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	9	86	theme	EL	1577:1578	arg1	%					1599:1599	EQE <1%	1593:1599	EQE <1%	1593:1599	The TCTA containing exciplex demonstrated moderate energy offsets (0.88-1.03 eV) and EL efficiency (~4%), while mCP systems showed the poorest EL performance (EQE <1%) and shortest delayed lifetime of <100 ns due to inadequate driving force of 0.47-0.75 eV for efficient exciplex formation.
31001516	3	87	theme	deep-blue	622:630	arg1	emission					632:639	deep-blue emission	622:639	deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm	622:695	24iPBIOXD and iTPBIOXD exhibited deep-blue emission with peak at 421 and 459 nm in solution, 397 and 419 nm at film state, respectively.
31001516	1	88	theme	efficient	295:303	arg1	crossing					325:332	efficient reverse intersystem crossing	295:332	efficient reverse intersystem crossing	295:332	Recently, donor/acceptor type exciplex have attracted considerable interests due to the low driving voltages and small singlet-triplet bandgaps for efficient reverse intersystem crossing to achieve 100% excitons for high efficiency thermally activated delayed fluorescence (TADF) OLEDs.
30203874	3	0	theme	rigid	669:673	arg1	units					680:684	rigid BPTI units	669:684	rigid BPTI units	669:684	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	1	1	theme	N-linked	136:143	arg1	dimers					173:178	N-linked benzo[ghi]-perylenetriimide dimers	136:178	N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position	136:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	1	theme	N-linked	136:143	arg1	N					134:134	twisted N	126:134	twisted N	126:134	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	1	theme	N-linked	136:143	arg1	t-BPTI					181:186	t-BPTI	181:186	t-BPTI	181:186	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	4	2	theme	organic	865:871	arg1	photovoltaics					873:885	solution-processed bulk heterojunction organic photovoltaics	826:885	solution-processed bulk heterojunction organic photovoltaics (OPV)	826:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	2	theme	organic	865:871	arg1	OPV					888:890	OPV	888:890	OPV	888:890	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	1	3	theme	alkyl	228:232	arg1	chain					239:243	the α-branched alkyl side chain	213:243	the α-branched alkyl side chain at the six-membered imide ring position	213:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	4	4	theme	%	939:939	arg1	efficiency					920:929	a power conversion efficiency	901:929	a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments	901:1024	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	1	5	theme	benzo[ghi	145:153	arg1	dimers					173:178	N-linked benzo[ghi]-perylenetriimide dimers	136:178	N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position	136:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	5	theme	benzo[ghi	145:153	arg1	N					134:134	twisted N	126:134	twisted N	126:134	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	5	theme	benzo[ghi	145:153	arg1	t-BPTI					181:186	t-BPTI	181:186	t-BPTI	181:186	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	6	theme	side	234:237	arg1	chain					239:243	the α-branched alkyl side chain	213:243	the α-branched alkyl side chain at the six-membered imide ring position	213:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	0	7	theme	Organic	91:97	arg1	Photovoltaics					99:111	Fullerene-Free Organic Photovoltaics	76:111	Fullerene-Free Organic Photovoltaics	76:111	The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics.
30203874	4	8	from	acceptor	814:821	arg1	photovoltaics					873:885	solution-processed bulk heterojunction organic photovoltaics	826:885	solution-processed bulk heterojunction organic photovoltaics (OPV)	826:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	8	from	acceptor	814:821	arg1	OPV					888:890	OPV	888:890	OPV	888:890	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	1	9	from	position	276:283	arg1	lengths					202:208	various lengths	194:208	various lengths of the α-branched alkyl side chain at the six-membered imide ring position	194:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	9	from	position	276:283	arg1	chain					239:243	the α-branched alkyl side chain	213:243	the α-branched alkyl side chain at the six-membered imide ring position	213:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	3	10	theme	molecular	523:531	arg1	geometry					533:540	The twisted molecular geometry	511:540	The twisted molecular geometry with two nearly perpendicular BPTI planes	511:582	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	1	11	theme	chain	239:243	arg1	lengths					202:208	various lengths	194:208	various lengths of the α-branched alkyl side chain at the six-membered imide ring position	194:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	0	12	theme	Fullerene-Free	76:89	arg1	Photovoltaics					99:111	Fullerene-Free Organic Photovoltaics	76:111	Fullerene-Free Organic Photovoltaics	76:111	The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics.
30203874	4	13	theme	solution-processed	826:843	arg1	photovoltaics					873:885	solution-processed bulk heterojunction organic photovoltaics	826:885	solution-processed bulk heterojunction organic photovoltaics (OPV)	826:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	13	theme	solution-processed	826:843	arg1	OPV					888:890	OPV	888:890	OPV	888:890	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	14	theme	t-BPTI-3	715:722	arg1	unit					724:727	The acceptor t-BPTI-3 unit	702:727	The acceptor t-BPTI-3 unit with the longest alkyl side chains	702:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	14	theme	t-BPTI-3	715:722	arg1	acceptor					814:821	an efficient electron acceptor	792:821	an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV)	792:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	3	15	theme	blend	689:693	arg1	films					695:699	blend films	689:699	blend films	689:699	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	2	16	theme	energy	373:378	arg1	level					380:384	the low-lying LUMO energy level	354:384	the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm	354:508	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	4	17	theme	conversion	909:918	arg1	efficiency					920:929	a power conversion efficiency	901:929	a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments	901:1024	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	3	18	theme	BPTI	675:678	arg1	units					680:684	rigid BPTI units	669:684	rigid BPTI units	669:684	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	1	19	theme	-perylenetriimide	155:171	arg1	dimers					173:178	N-linked benzo[ghi]-perylenetriimide dimers	136:178	N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position	136:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	19	theme	-perylenetriimide	155:171	arg1	N					134:134	twisted N	126:134	twisted N	126:134	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	19	theme	-perylenetriimide	155:171	arg1	t-BPTI					181:186	t-BPTI	181:186	t-BPTI	181:186	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	0	20	theme	Twisted	4:10	arg1	-Perylenetriimide					22:38	The Twisted Benzo[ghi]-Perylenetriimide	0:38	The Twisted Benzo[ghi]-Perylenetriimide	0:38	The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics.
30203874	3	21	theme	units	680:684	arg1	self-aggregation					649:664	the self-aggregation	645:664	the self-aggregation of rigid BPTI units in blend films	645:699	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	4	22	theme	electron	805:812	arg1	unit					724:727	The acceptor t-BPTI-3 unit	702:727	The acceptor t-BPTI-3 unit with the longest alkyl side chains	702:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	22	theme	electron	805:812	arg1	acceptor					814:821	an efficient electron acceptor	792:821	an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV)	792:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	23	theme	power	903:907	arg1	efficiency					920:929	a power conversion efficiency	901:929	a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments	901:1024	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	2	24	theme	low-lying	358:366	arg1	level					380:384	the low-lying LUMO energy level	354:384	the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm	354:508	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	4	25	theme	efficient	795:803	arg1	unit					724:727	The acceptor t-BPTI-3 unit	702:727	The acceptor t-BPTI-3 unit with the longest alkyl side chains	702:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	25	theme	efficient	795:803	arg1	acceptor					814:821	an efficient electron acceptor	792:821	an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV)	792:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	3	26	theme	twisted	515:521	arg1	geometry					533:540	The twisted molecular geometry	511:540	The twisted molecular geometry with two nearly perpendicular BPTI planes	511:582	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	1	27	theme	six-membered	252:263	arg1	ring					271:274	the six-membered imide ring	248:274	the six-membered imide ring position	248:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	28	link	N-linked	136:143	arg1	dimers					173:178	N-linked benzo[ghi]-perylenetriimide dimers	136:178	N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position	136:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	28	link	N-linked	136:143	arg1	N					134:134	twisted N	126:134	twisted N	126:134	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	28	link	N-linked	136:143	arg1	t-BPTI					181:186	t-BPTI	181:186	t-BPTI	181:186	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	4	29	theme	acceptor	706:713	arg1	unit					724:727	The acceptor t-BPTI-3 unit	702:727	The acceptor t-BPTI-3 unit with the longest alkyl side chains	702:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	29	theme	acceptor	706:713	arg1	acceptor					814:821	an efficient electron acceptor	792:821	an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV)	792:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	0	30	theme	Benzo[ghi	12:20	arg1	-Perylenetriimide					22:38	The Twisted Benzo[ghi]-Perylenetriimide	0:38	The Twisted Benzo[ghi]-Perylenetriimide	0:38	The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics.
30203874	1	31	theme	imide	265:269	arg1	ring					271:274	the six-membered imide ring	248:274	the six-membered imide ring position	248:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	3	32	theme	favorable	595:603	arg1	separation					621:630	a favorable nanoscale phase separation	593:630	a favorable nanoscale phase separation	593:630	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	2	33	theme	-3.78 eV	389:396	arg1	level					380:384	the low-lying LUMO energy level	354:384	the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm	354:508	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	4	34	theme	conjugated	952:961	arg1	PTB7-Th					971:977	conjugated polymer PTB7-Th	952:977	conjugated polymer PTB7-Th	952:977	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	34	theme	conjugated	952:961	arg1	donor					986:990	the donor	982:990	the donor	982:990	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	1	35	theme	ring	271:274	arg1	position					276:283	the six-membered imide ring position	248:283	the six-membered imide ring position	248:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	3	36	theme	nanoscale	605:613	arg1	separation					621:630	a favorable nanoscale phase separation	593:630	a favorable nanoscale phase separation	593:630	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	2	37	theme	PC61	428:431	arg1	-3.71 eV					437:444	-3.71 eV	437:444	-3.71 eV	437:444	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	2	37	theme	PC61	428:431	arg1	BM					433:434	PC61 BM	428:434	PC61 BM (-3.71 eV)	428:445	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	3	38	from	self-aggregation	649:664	arg1	films					695:699	blend films	689:699	blend films	689:699	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	1	39	theme	various	194:200	arg1	lengths					202:208	various lengths	194:208	various lengths of the α-branched alkyl side chain at the six-membered imide ring position	194:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	2	40	theme	optical	467:473	arg1	absorption					475:484	intensive optical absorption	457:484	intensive optical absorption in the range 350-500 nm	457:508	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	1	41	with	dimers	173:178	arg1	lengths					202:208	various lengths	194:208	various lengths of the α-branched alkyl side chain at the six-membered imide ring position	194:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	2	42	theme	intensive	457:465	arg1	absorption					475:484	intensive optical absorption	457:484	intensive optical absorption in the range 350-500 nm	457:508	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	4	43	theme	polymer	963:969	arg1	PTB7-Th					971:977	conjugated polymer PTB7-Th	952:977	conjugated polymer PTB7-Th	952:977	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	43	theme	polymer	963:969	arg1	donor					986:990	the donor	982:990	the donor	982:990	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	44	theme	heterojunction	850:863	arg1	photovoltaics					873:885	solution-processed bulk heterojunction organic photovoltaics	826:885	solution-processed bulk heterojunction organic photovoltaics (OPV)	826:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	44	theme	heterojunction	850:863	arg1	OPV					888:890	OPV	888:890	OPV	888:890	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	3	45	with	geometry	533:540	arg1	planes					577:582	two nearly perpendicular BPTI planes	547:582	two nearly perpendicular BPTI planes	547:582	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	4	46	theme	bulk	845:848	arg1	photovoltaics					873:885	solution-processed bulk heterojunction organic photovoltaics	826:885	solution-processed bulk heterojunction organic photovoltaics (OPV)	826:891	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	46	theme	bulk	845:848	arg1	OPV					888:890	OPV	888:890	OPV	888:890	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	4	47	theme	side	752:755	arg1	chains					757:762	the longest alkyl side chains	734:762	the longest alkyl side chains	734:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	1	48	from	lengths	202:208	arg1	position					276:283	the six-membered imide ring position	248:283	the six-membered imide ring position	248:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	4	49	theme	alkyl	746:750	arg1	chains					757:762	the longest alkyl side chains	734:762	the longest alkyl side chains	734:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	3	50	theme	BPTI	572:575	arg1	planes					577:582	two nearly perpendicular BPTI planes	547:582	two nearly perpendicular BPTI planes	547:582	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	3	51	theme	phase	615:619	arg1	separation					621:630	a favorable nanoscale phase separation	593:630	a favorable nanoscale phase separation	593:630	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	4	52	theme	longest	738:744	arg1	chains					757:762	the longest alkyl side chains	734:762	the longest alkyl side chains	734:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	1	53	theme	twisted	126:132	arg1	dimers					173:178	N-linked benzo[ghi]-perylenetriimide dimers	136:178	N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position	136:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	1	53	theme	twisted	126:132	arg1	N					134:134	twisted N	126:134	twisted N	126:134	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	2	54	from	absorption	475:484	arg1	range					493:497	the range 350-500 nm	489:508	the range 350-500 nm	489:508	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	0	55	theme	Electron	54:61	arg1	Acceptor					63:70	a 3D Electron Acceptor	49:70	a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics	49:111	The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics.
30203874	1	56	theme	N	134:134	arg1	series					116:121	A series	114:121	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position	114:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
30203874	2	57	theme	LUMO	368:371	arg1	level					380:384	the low-lying LUMO energy level	354:384	the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm	354:508	These compounds showed the low-lying LUMO energy level of -3.78 eV, which was similar to that of PC61 BM (-3.71 eV), but with intensive optical absorption in the range 350-500 nm.
30203874	4	58	with	unit	724:727	arg1	chains					757:762	the longest alkyl side chains	734:762	the longest alkyl side chains	734:762	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	0	59	theme	3D	51:52	arg1	Acceptor					63:70	a 3D Electron Acceptor	49:70	a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics	49:111	The Twisted Benzo[ghi]-Perylenetriimide Dimer as a 3D Electron Acceptor for Fullerene-Free Organic Photovoltaics.
30203874	3	60	theme	perpendicular	558:570	arg1	planes					577:582	two nearly perpendicular BPTI planes	547:582	two nearly perpendicular BPTI planes	547:582	The twisted molecular geometry with two nearly perpendicular BPTI planes achieved a favorable nanoscale phase separation by relieving the self-aggregation of rigid BPTI units in blend films.
30203874	4	61	theme	additional	1004:1013	arg1	treatments					1015:1024	additional treatments	1004:1024	additional treatments	1004:1024	The acceptor t-BPTI-3 unit with the longest alkyl side chains has been demonstrated to be an efficient electron acceptor in solution-processed bulk heterojunction organic photovoltaics (OPV), giving a power conversion efficiency of 3.68 % when using conjugated polymer PTB7-Th as the donor and without additional treatments.
30203874	1	62	theme	α-branched	217:226	arg1	chain					239:243	the α-branched alkyl side chain	213:243	the α-branched alkyl side chain at the six-membered imide ring position	213:283	A series of twisted N,N-linked benzo[ghi]-perylenetriimide dimers (t-BPTI) with various lengths of the α-branched alkyl side chain at the six-membered imide ring position was designed, synthesized, and characterized.
29325746	3	0	theme	superfamily	610:620	arg1	domain					592:597	putative conserved domain	573:597	putative conserved domain of apyrase superfamily	573:620	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	3	0	theme	superfamily	610:620	arg1	superfamily					610:620	apyrase superfamily	602:620	apyrase superfamily	602:620	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	2	1	gly	glycoprotein	317:328	arg1	glycoprotein					317:328	a high molecular weight (79.4 kDa) monomeric glycoprotein	272:328	a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A	272:435	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	1	gly	glycoprotein	317:328	arg1	It					266:267	It	266:267	It	266:267	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	2	theme	N-linked	374:381	arg1	oligosaccharides					383:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	3	contain	contains	335:342	arg1	glycoprotein					317:328	a high molecular weight (79.4 kDa) monomeric glycoprotein	272:328	a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A	272:435	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	3	contain	contains	335:342	arg1	It					266:267	It	266:267	It	266:267	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	3	contain	contains	335:342	arg2	oligosaccharides					383:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	5	4	theme	turnover	956:963	arg1	Kcat					973:976	Kcat	973:976	Kcat	973:976	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	4	theme	turnover	956:963	arg1	number					965:970	a turnover number	954:970	a turnover number (Kcat) of 24,600 min-1	954:993	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	0	5	from	venom	122:126	arg1	Ruviapyrase					63:73	Ruviapyrase	63:73	Ruviapyrase	63:73	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	0	5	from	venom	122:126	arg1	apyrase					54:60	a snake venom apyrase	40:60	a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom	40:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	0	5	from	venom	122:126	arg1	characterization					20:35	the characterization	16:35	the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom	16:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	6	6	with	interaction	1038:1048	arg1	ATP					1070:1072	ATP	1070:1072	ATP	1070:1072	Spectrofluorometric analysis demonstrated interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM, respectively.
29325746	6	6	with	interaction	1038:1048	arg1	ADP					1078:1080	ADP	1078:1080	ADP	1078:1080	Spectrofluorometric analysis demonstrated interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM, respectively.
29325746	5	7	theme	Pi released min-1	917:933	arg1	2.54 μM					895:901	2.54 μM	895:901	2.54 μM	895:901	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	7	theme	Pi released min-1	917:933	arg1	values					855:860	The Km and Vmax values	839:860	values	855:860	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	7	theme	Pi released min-1	917:933	arg1	615 μM					907:912	615 μM	907:912	615 μM	907:912	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	3	8	theme	LC-MS/MS	442:449	arg1	analysis					451:458	The LC-MS/MS analysis	438:458	The LC-MS/MS analysis	438:458	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	6	9	theme	Ruviapyrase	1053:1063	arg1	interaction					1038:1048	interaction	1038:1048	interaction of Ruviapyrase with ATP and ADP	1038:1080	Spectrofluorometric analysis demonstrated interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM, respectively.
29325746	2	10	theme	Concanavalin	422:433	arg1	A					435:435	Concanavalin A	422:435	Concanavalin A	422:435	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	6	11	theme	Kd	1085:1086	arg1	values					1088:1093	Kd values	1085:1093	Kd values	1085:1093	Spectrofluorometric analysis demonstrated interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM, respectively.
29325746	5	12	with	615 μM	907:912	arg1	Kcat					973:976	Kcat	973:976	Kcat	973:976	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	12	with	615 μM	907:912	arg1	number					965:970	a turnover number	954:970	a turnover number (Kcat) of 24,600 min-1	954:993	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	13	theme	24,600 min-1	982:993	arg1	Kcat					973:976	Kcat	973:976	Kcat	973:976	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	13	theme	24,600 min-1	982:993	arg1	number					965:970	a turnover number	954:970	a turnover number (Kcat) of 24,600 min-1	954:993	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	8	14	theme	deaggregation	1406:1418	arg1	property					1420:1427	platelet deaggregation property	1397:1427	platelet deaggregation property	1397:1427	The catalytic activity and platelet deaggregation property of Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by commercial monovalent and polyvalent antivenom.
29325746	4	15	theme	greater	694:700	arg1	p < .05					710:716	p < .05	710:716	p < .05	710:716	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	4	15	theme	greater	694:700	arg1	extent					702:707	a significantly greater extent	678:707	a significantly greater extent (p < .05)	678:717	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	7	16	theme	haemolytic	1211:1220	arg1	activity					1222:1229	haemolytic activity	1211:1229	haemolytic activity	1211:1229	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	0	17	theme	Indian	81:86	arg1	venom					122:126	Indian Russell's viper (Daboia russelii) venom	81:126	Indian Russell's viper (Daboia russelii) venom	81:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	0	18	theme	First	0:4	arg1	report					6:11	First report	0:11	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.	0:127	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	8	19	theme	platelet	1397:1404	arg1	property					1420:1427	platelet deaggregation property	1397:1427	platelet deaggregation property	1397:1427	The catalytic activity and platelet deaggregation property of Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by commercial monovalent and polyvalent antivenom.
29325746	1	20	theme	novel	131:135	arg1	apyrase					137:143	A novel apyrase	129:143	A novel apyrase from Russell's viper venom (RVV)	129:176	A novel apyrase from Russell's viper venom (RVV) was purified and characterized, and it was named Ruviapyrase (Russell's viper apyrase).
29325746	2	21	theme	neutral	349:355	arg1	sugars					357:362	neutral sugars	349:362	2.4% neutral sugars	344:362	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	0	22	from	characterization	20:35	arg1	venom					122:126	Indian Russell's viper (Daboia russelii) venom	81:126	Indian Russell's viper (Daboia russelii) venom	81:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	5	23	with	2.54 μM	895:901	arg1	Kcat					973:976	Kcat	973:976	Kcat	973:976	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	23	with	2.54 μM	895:901	arg1	number					965:970	a turnover number	954:970	a turnover number (Kcat) of 24,600 min-1	954:993	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	2	24	theme	weight	289:294	arg1	glycoprotein					317:328	a high molecular weight (79.4 kDa) monomeric glycoprotein	272:328	a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A	272:435	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	24	theme	weight	289:294	arg1	It					266:267	It	266:267	It	266:267	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	25	theme	%	347:347	arg1	oligosaccharides					383:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	26	dep	%	347:347	arg1	sugars					357:362	neutral sugars	349:362	2.4% neutral sugars	344:362	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	5	27	theme	Km	843:844	arg1	2.54 μM					895:901	2.54 μM	895:901	2.54 μM	895:901	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	27	theme	Km	843:844	arg1	values					855:860	The Km and Vmax values	839:860	values	855:860	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	3	28	from	protein	481:487	arg1	database					505:512	NCBI protein database	492:512	NCBI protein database	492:512	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	2	29	theme	molecular	279:287	arg1	79.4 kDa					297:304	79.4 kDa	297:304	79.4 kDa	297:304	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	29	theme	molecular	279:287	arg1	weight					289:294	high molecular weight	274:294	a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A	272:435	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	7	30	theme	strong	1272:1277	arg1	activity					1292:1299	marginal anticoagulant and strong antiplatelet activity	1245:1299	activity	1292:1299	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	0	31	theme	viper	98:102	arg1	venom					122:126	Indian Russell's viper (Daboia russelii) venom	81:126	Indian Russell's viper (Daboia russelii) venom	81:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	7	32	theme	ADP-induced	1336:1346	arg1	aggregation					1357:1367	the ADP-induced platelet aggregation	1332:1367	the ADP-induced platelet aggregation	1332:1367	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	8	33	theme	catalytic	1374:1382	arg1	activity					1384:1391	The catalytic activity	1370:1391	The catalytic activity	1370:1391	The catalytic activity and platelet deaggregation property of Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by commercial monovalent and polyvalent antivenom.
29325746	5	34	theme	Vmax	850:853	arg1	2.54 μM					895:901	2.54 μM	895:901	2.54 μM	895:901	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	5	34	theme	Vmax	850:853	arg1	values					855:860	The Km and Vmax values	839:860	values	855:860	The Km and Vmax values for Ruviapyrase towards ATP were 2.54 μM and 615 μM of Pi released min-1, respectively with a turnover number (Kcat) of 24,600 min-1.
29325746	6	35	theme	Spectrofluorometric	996:1014	arg1	analysis					1016:1023	Spectrofluorometric analysis	996:1023	Spectrofluorometric analysis	996:1023	Spectrofluorometric analysis demonstrated interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM, respectively.
29325746	2	36	theme	%	372:372	arg1	oligosaccharides					383:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	0	37	theme	Daboia	105:110	arg1	venom					122:126	Indian Russell's viper (Daboia russelii) venom	81:126	Indian Russell's viper (Daboia russelii) venom	81:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	2	38	theme	monomeric	307:315	arg1	glycoprotein					317:328	a high molecular weight (79.4 kDa) monomeric glycoprotein	272:328	a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A	272:435	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	38	theme	monomeric	307:315	arg1	It					266:267	It	266:267	It	266:267	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	3	39	theme	NCBI	492:495	arg1	database					505:512	NCBI protein database	492:512	NCBI protein database	492:512	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	1	40	theme	viper	160:164	arg1	RVV					173:175	RVV	173:175	RVV	173:175	A novel apyrase from Russell's viper venom (RVV) was purified and characterized, and it was named Ruviapyrase (Russell's viper apyrase).
29325746	1	40	theme	viper	160:164	arg1	venom					166:170	Russell's viper venom	150:170	Russell's viper venom (RVV)	150:176	A novel apyrase from Russell's viper venom (RVV) was purified and characterized, and it was named Ruviapyrase (Russell's viper apyrase).
29325746	0	41	theme	characterization	20:35	arg1	report					6:11	First report	0:11	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.	0:127	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	4	42	theme	activities	827:836	arg1	devoid					779:784	devoid	779:784	devoid	779:784	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	3	43	theme	de	533:534	arg1	sequences					541:549	some de novo sequences	528:549	some de novo sequences of Ruviapyrase	528:564	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	3	44	theme	protein	497:503	arg1	database					505:512	NCBI protein database	492:512	NCBI protein database	492:512	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	0	45	theme	snake	42:46	arg1	Ruviapyrase					63:73	Ruviapyrase	63:73	Ruviapyrase	63:73	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	0	45	theme	snake	42:46	arg1	apyrase					54:60	a snake venom apyrase	40:60	a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom	40:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	4	46	theme	adenosine	734:742	arg1	ADP					757:759	ADP	757:759	ADP	757:759	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	4	46	theme	adenosine	734:742	arg1	diphosphate					744:754	adenosine diphosphate	734:754	adenosine diphosphate (ADP)	734:760	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	2	47	link	N-linked	374:381	arg1	oligosaccharides					383:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	2.4% neutral sugars and 58.4% N-linked oligosaccharides	344:398	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	7	48	theme	cancer	1186:1191	arg1	cells					1201:1205	breast cancer (MCF-7) cells	1179:1205	breast cancer (MCF-7) cells	1179:1205	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	0	49	theme	russelii	112:119	arg1	venom					122:126	Indian Russell's viper (Daboia russelii) venom	81:126	Indian Russell's viper (Daboia russelii) venom	81:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	3	50	theme	putative	573:580	arg1	domain					592:597	putative conserved domain	573:597	putative conserved domain of apyrase superfamily	573:620	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	3	50	theme	putative	573:580	arg1	superfamily					610:620	apyrase superfamily	602:620	apyrase superfamily	602:620	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	7	51	theme	antiplatelet	1279:1290	arg1	activity					1292:1299	marginal anticoagulant and strong antiplatelet activity	1245:1299	activity	1292:1299	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	3	52	theme	apyrase	602:608	arg1	superfamily					610:620	apyrase superfamily	602:620	apyrase superfamily	602:620	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	8	53	theme	commercial	1513:1522	arg1	monovalent					1524:1533	commercial monovalent	1513:1533	commercial monovalent	1513:1533	The catalytic activity and platelet deaggregation property of Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by commercial monovalent and polyvalent antivenom.
29325746	4	54	theme	5'-nucleotidase	789:803	arg1	devoid					779:784	devoid	779:784	devoid	779:784	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	3	55	theme	conserved	582:590	arg1	domain					592:597	putative conserved domain	573:597	putative conserved domain of apyrase superfamily	573:620	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	3	55	theme	conserved	582:590	arg1	superfamily					610:620	apyrase superfamily	602:620	apyrase superfamily	602:620	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	6	56	theme	1.25 nM	1110:1116	arg1	values					1088:1093	Kd values	1085:1093	Kd values	1085:1093	Spectrofluorometric analysis demonstrated interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM, respectively.
29325746	4	57	theme	adenosine	646:654	arg1	ATP					670:672	ATP	670:672	ATP	670:672	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	4	57	theme	adenosine	646:654	arg1	triphosphate					656:667	adenosine triphosphate	646:667	adenosine triphosphate (ATP)	646:673	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	3	58	dep	de	533:534	arg1	novo					536:539	novo	536:539	novo	536:539	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	7	59	theme	platelet	1348:1355	arg1	aggregation					1357:1367	the ADP-induced platelet aggregation	1332:1367	the ADP-induced platelet aggregation	1332:1367	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	3	60	theme	Ruviapyrase	554:564	arg1	sequences					541:549	some de novo sequences	528:549	some de novo sequences of Ruviapyrase	528:564	The LC-MS/MS analysis did not identify any protein in NCBI protein database, nevertheless some de novo sequences of Ruviapyrase showed putative conserved domain of apyrase superfamily.
29325746	8	61	theme	Ruviapyrase	1432:1442	arg1	activity					1384:1391	The catalytic activity	1370:1391	The catalytic activity	1370:1391	The catalytic activity and platelet deaggregation property of Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by commercial monovalent and polyvalent antivenom.
29325746	8	61	theme	Ruviapyrase	1432:1442	arg1	property					1420:1427	platelet deaggregation property	1397:1427	platelet deaggregation property	1397:1427	The catalytic activity and platelet deaggregation property of Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by commercial monovalent and polyvalent antivenom.
29325746	7	62	theme	breast	1179:1184	arg1	MCF-7					1194:1198	MCF-7	1194:1198	MCF-7	1194:1198	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	7	62	theme	breast	1179:1184	arg1	cancer					1186:1191	breast cancer	1179:1191	breast cancer (MCF-7) cells	1179:1205	Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7) cells and haemolytic activity, it exhibited marginal anticoagulant and strong antiplatelet activity, and dose-dependently reversed the ADP-induced platelet aggregation.
29325746	0	63	theme	apyrase	54:60	arg1	characterization					20:35	the characterization	16:35	the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom	16:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	4	64	theme	phosphodiesterase	809:825	arg1	activities					827:836	phosphodiesterase activities	809:836	phosphodiesterase activities	809:836	Ruviapyrase hydrolysed adenosine triphosphate (ATP) to a significantly greater extent (p < .05) as compared to adenosine diphosphate (ADP); however, it was devoid of 5'-nucleotidase and phosphodiesterase activities.
29325746	6	65	theme	0.92 nM	1098:1104	arg1	values					1088:1093	Kd values	1085:1093	Kd values	1085:1093	Spectrofluorometric analysis demonstrated interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM, respectively.
29325746	2	66	theme	high	274:277	arg1	79.4 kDa					297:304	79.4 kDa	297:304	79.4 kDa	297:304	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	2	66	theme	high	274:277	arg1	weight					289:294	high molecular weight	274:294	a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A	272:435	It is a high molecular weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and 58.4% N-linked oligosaccharides and strongly binds to Concanavalin A.
29325746	0	67	theme	venom	48:52	arg1	Ruviapyrase					63:73	Ruviapyrase	63:73	Ruviapyrase	63:73	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	0	67	theme	venom	48:52	arg1	apyrase					54:60	a snake venom apyrase	40:60	a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom	40:126	First report of the characterization of a snake venom apyrase (Ruviapyrase) from Indian Russell's viper (Daboia russelii) venom.
29325746	1	68	theme	viper	250:254	arg1	apyrase					256:262	Russell's viper apyrase	240:262	Russell's viper apyrase	240:262	A novel apyrase from Russell's viper venom (RVV) was purified and characterized, and it was named Ruviapyrase (Russell's viper apyrase).
29325746	1	68	theme	viper	250:254	arg1	Ruviapyrase					227:237	Ruviapyrase	227:237	Ruviapyrase (Russell's viper apyrase)	227:263	A novel apyrase from Russell's viper venom (RVV) was purified and characterized, and it was named Ruviapyrase (Russell's viper apyrase).
29325746	8	69	theme	polyvalent	1539:1548	arg1	antivenom					1550:1558	polyvalent antivenom	1539:1558	polyvalent antivenom	1539:1558	The catalytic activity and platelet deaggregation property of Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by commercial monovalent and polyvalent antivenom.
31188144	9	0	theme	A	952:952	arg1	treatment					954:962	Neuraminidase A treatment	938:962	Neuraminidase A treatment	938:962	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	14	1	theme	PNGase	1378:1383	arg1	treatment					1387:1395	PNGase F treatment	1378:1395	PNGase F treatment	1378:1395	Platelet surface sialic acid was increased after PNGase F treatment.
31188144	17	2	dep	enhances	1600:1607	arg1	suggest					1651:1657	suggest	1651:1657	suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis	1651:1750	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	9	3	theme	sialic	971:976	arg1	decrease					989:996	sialic acid level decrease	971:996	sialic acid level decrease	971:996	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	13	4	dep	increased	1307:1315	arg1	P < 0.05					1318:1325	P < 0.05	1318:1325	P < 0.05	1318:1325	Platelet-granulocytes aggregates and platelet-monocytes aggregates increased (P < 0.05).
31188144	3	5	theme	altered	355:361	arg1	glycosylation					363:375	altered glycosylation	355:375	altered glycosylation	355:375	In this study, we further investigated whether altered glycosylation affects platelet function.
31188144	7	6	theme	platelet	663:670	arg1	adhesion					672:679	platelet adhesion	663:679	platelet adhesion to von Willebrand factor (vWF)	663:710	The activation and platelet adhesion to von Willebrand factor (vWF) was measured by flow cytometry.
31188144	0	7	contain	has	57:59	arg1	glycosylation					21:33	The platelet surface glycosylation	0:33	The platelet surface glycosylation caused by glycosidase	0:55	The platelet surface glycosylation caused by glycosidase has a strong impact on platelet function.
31188144	0	7	contain	has	57:59	arg2	impact					70:75	a strong impact	61:75	a strong impact	61:75	The platelet surface glycosylation caused by glycosidase has a strong impact on platelet function.
31188144	2	8	theme	heart	293:297	arg1	disease					299:305	coronary heart disease	284:305	coronary heart disease	284:305	Our previous study found that platelet surface glycosylation is altered in coronary heart disease.
31188144	8	9	theme	platelet-leukocyte	869:886	arg1	PLAs					900:903	PLAs	900:903	PLAs	900:903	Platelet aggregation induced by ADP, arachidonic acid and collagen was detected through light transmission aggregometry, and platelet-leukocyte aggregates (PLAs) was detected by flow cytometry.
31188144	8	9	theme	platelet-leukocyte	869:886	arg1	aggregates					888:897	platelet-leukocyte aggregates	869:897	platelet-leukocyte aggregates (PLAs)	869:904	Platelet aggregation induced by ADP, arachidonic acid and collagen was detected through light transmission aggregometry, and platelet-leukocyte aggregates (PLAs) was detected by flow cytometry.
31188144	0	10	theme	platelet	80:87	arg1	function					89:96	platelet function	80:96	platelet function	80:96	The platelet surface glycosylation caused by glycosidase has a strong impact on platelet function.
31188144	17	11	theme	increased	1723:1731	arg1	risk					1733:1736	the increased risk	1719:1736	the increased risk of thrombosis	1719:1750	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	2	12	theme	coronary	284:291	arg1	disease					299:305	coronary heart disease	284:305	coronary heart disease	284:305	Our previous study found that platelet surface glycosylation is altered in coronary heart disease.
31188144	12	13	theme	ADP-induced	1169:1179	arg1	aggregation					1190:1200	ADP-induced platelet aggregation	1169:1200	ADP-induced platelet aggregation	1169:1200	ADP-induced platelet aggregation was significantly reduced (P < 0.05).
31188144	7	14	theme	flow	728:731	arg1	cytometry					733:741	flow cytometry	728:741	flow cytometry	728:741	The activation and platelet adhesion to von Willebrand factor (vWF) was measured by flow cytometry.
31188144	9	15	theme	acid	978:981	arg1	decrease					989:996	sialic acid level decrease	971:996	sialic acid level decrease	971:996	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	13	16	theme	platelet-monocytes	1277:1294	arg1	aggregates					1296:1305	platelet-monocytes aggregates	1277:1305	platelet-monocytes aggregates	1277:1305	Platelet-granulocytes aggregates and platelet-monocytes aggregates increased (P < 0.05).
31188144	17	17	theme	high	1690:1693	arg1	reactivity					1704:1713	high platelet reactivity	1690:1713	high platelet reactivity	1690:1713	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	5	18	theme	neuraminidase	514:526	arg1	A					528:528	neuraminidase A	514:528	neuraminidase A	514:528	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	9	19	theme	level	983:987	arg1	decrease					989:996	sialic acid level decrease	971:996	sialic acid level decrease	971:996	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	14	20	theme	sialic	1346:1351	arg1	acid					1353:1356	Platelet surface sialic acid	1329:1356	Platelet surface sialic acid	1329:1356	Platelet surface sialic acid was increased after PNGase F treatment.
31188144	1	21	dep	surface	110:116	arg1	defects					132:138	glycosylation defects	118:138	: Platelet surface glycosylation defects	99:138	: Platelet surface glycosylation defects has been reported to be significantly associated with many diseases.
31188144	16	22	theme	PNGase	1532:1537	arg1	F					1539:1539	PNGase F	1532:1539	PNGase F	1532:1539	There is no difference in the binding of vWF and PLAs for PNGase F treated platelet.
31188144	9	23	theme	level	1014:1018	arg1	increase					1020:1027	β-galactose level increase	1002:1027	β-galactose level increase	1002:1027	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	0	24	theme	platelet	4:11	arg1	glycosylation					21:33	The platelet surface glycosylation	0:33	The platelet surface glycosylation caused by glycosidase	0:55	The platelet surface glycosylation caused by glycosidase has a strong impact on platelet function.
31188144	14	25	theme	surface	1338:1344	arg1	acid					1353:1356	Platelet surface sialic acid	1329:1356	Platelet surface sialic acid	1329:1356	Platelet surface sialic acid was increased after PNGase F treatment.
31188144	12	26	theme	platelet	1181:1188	arg1	aggregation					1190:1200	ADP-induced platelet aggregation	1169:1200	ADP-induced platelet aggregation	1169:1200	ADP-induced platelet aggregation was significantly reduced (P < 0.05).
31188144	6	27	theme	platelet	621:628	arg1	function					590:597	The function	586:597	The function of the enzyme-treated platelet	586:628	The function of the enzyme-treated platelet was measured.
31188144	14	28	theme	Platelet	1329:1336	arg1	acid					1353:1356	Platelet surface sialic acid	1329:1356	Platelet surface sialic acid	1329:1356	Platelet surface sialic acid was increased after PNGase F treatment.
31188144	5	29	theme	sialic	487:492	arg1	acid					494:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	11	30	theme	Platelet	1104:1111	arg1	adhesion					1113:1120	Platelet adhesion	1104:1120	Platelet adhesion to vWF	1104:1127	Platelet adhesion to vWF was increased significantly (P < 0.05).
31188144	6	31	theme	enzyme-treated	606:619	arg1	platelet					621:628	the enzyme-treated platelet	602:628	the enzyme-treated platelet	602:628	The function of the enzyme-treated platelet was measured.
31188144	11	32	dep	increased	1133:1141	arg1	P < 0.05					1158:1165	P < 0.05	1158:1165	P < 0.05	1158:1165	Platelet adhesion to vWF was increased significantly (P < 0.05).
31188144	3	33	gly	glycosylation	363:375	arg1	platelet					385:392	platelet function	385:401	platelet function	385:401	In this study, we further investigated whether altered glycosylation affects platelet function.
31188144	15	34	dep	reduced	1454:1460	arg1	P < 0.05					1463:1470	P < 0.05	1463:1470	P < 0.05	1463:1470	Platelet aggregation by all agonists were significantly reduced (P < 0.05).
31188144	17	35	theme	platelet	1695:1702	arg1	reactivity					1704:1713	high platelet reactivity	1690:1713	high platelet reactivity	1690:1713	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	1	36	theme	many	194:197	arg1	diseases					199:206	many diseases	194:206	many diseases	194:206	: Platelet surface glycosylation defects has been reported to be significantly associated with many diseases.
31188144	3	37	theme	platelet	385:392	arg1	function					394:401	platelet function	385:401	platelet function	385:401	In this study, we further investigated whether altered glycosylation affects platelet function.
31188144	17	38	theme	forming	1637:1643	arg1	PLAs					1645:1648	forming PLAs	1637:1648	forming PLAs	1637:1648	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	13	39	theme	Platelet-granulocytes	1240:1260	arg1	aggregates					1262:1271	Platelet-granulocytes aggregates	1240:1271	Platelet-granulocytes aggregates	1240:1271	Platelet-granulocytes aggregates and platelet-monocytes aggregates increased (P < 0.05).
31188144	10	40	theme	marker	1075:1080	arg1	CD62P					1082:1086	Activation marker CD62P	1064:1086	Activation marker CD62P	1064:1086	Activation marker CD62P did not change.
31188144	16	41	theme	PLAs	1523:1526	arg1	binding					1504:1510	the binding	1500:1510	the binding of vWF and PLAs for PNGase F treated platelet	1500:1556	There is no difference in the binding of vWF and PLAs for PNGase F treated platelet.
31188144	16	42	theme	vWF	1515:1517	arg1	binding					1504:1510	the binding	1500:1510	the binding of vWF and PLAs for PNGase F treated platelet	1500:1556	There is no difference in the binding of vWF and PLAs for PNGase F treated platelet.
31188144	15	43	theme	Platelet	1398:1405	arg1	aggregation					1407:1417	Platelet aggregation	1398:1417	Platelet aggregation by all agonists	1398:1433	Platelet aggregation by all agonists were significantly reduced (P < 0.05).
31188144	5	44	link	N-linked	535:542	arg1	oligosaccharides					544:559	N-linked oligosaccharides	535:559	N-linked oligosaccharides	535:559	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	12	45	dep	reduced	1220:1226	arg1	P < 0.05					1229:1236	P < 0.05	1229:1236	P < 0.05	1229:1236	ADP-induced platelet aggregation was significantly reduced (P < 0.05).
31188144	10	46	theme	Activation	1064:1073	arg1	CD62P					1082:1086	Activation marker CD62P	1064:1086	Activation marker CD62P	1064:1086	Activation marker CD62P did not change.
31188144	8	47	theme	flow	922:925	arg1	cytometry					927:935	flow cytometry	922:935	flow cytometry	922:935	Platelet aggregation induced by ADP, arachidonic acid and collagen was detected through light transmission aggregometry, and platelet-leukocyte aggregates (PLAs) was detected by flow cytometry.
31188144	0	48	theme	surface	13:19	arg1	glycosylation					21:33	The platelet surface glycosylation	0:33	The platelet surface glycosylation caused by glycosidase	0:55	The platelet surface glycosylation caused by glycosidase has a strong impact on platelet function.
31188144	17	49	theme	platelet	1609:1616	arg1	binding					1618:1624	platelet binding	1609:1624	platelet binding to vWF and forming PLAs	1609:1648	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	9	50	theme	β-galactose	1002:1012	arg1	increase					1020:1027	β-galactose level increase	1002:1027	β-galactose level increase	1002:1027	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	8	51	theme	Platelet	744:751	arg1	aggregation					753:763	Platelet aggregation	744:763	Platelet aggregation induced by ADP, arachidonic acid and collagen	744:809	Platelet aggregation induced by ADP, arachidonic acid and collagen was detected through light transmission aggregometry, and platelet-leukocyte aggregates (PLAs) was detected by flow cytometry.
31188144	8	52	theme	transmission	838:849	arg1	aggregometry					851:862	light transmission aggregometry	832:862	light transmission aggregometry	832:862	Platelet aggregation induced by ADP, arachidonic acid and collagen was detected through light transmission aggregometry, and platelet-leukocyte aggregates (PLAs) was detected by flow cytometry.
31188144	1	53	theme	Platelet	101:108	arg1	surface					110:116	: Platelet surface glycosylation defects	99:138	: Platelet surface glycosylation defects	99:138	: Platelet surface glycosylation defects has been reported to be significantly associated with many diseases.
31188144	9	54	theme	platelet	1046:1053	arg1	surface					1055:1061	platelet surface	1046:1061	platelet surface	1046:1061	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	4	55	theme	healthy	437:443	arg1	volunteers					445:454	ten healthy volunteers	433:454	ten healthy volunteers	433:454	Platelets were obtained from ten healthy volunteers.
31188144	2	56	theme	previous	213:220	arg1	study					222:226	Our previous study	209:226	Our previous study	209:226	Our previous study found that platelet surface glycosylation is altered in coronary heart disease.
31188144	5	57	theme	PNGase	576:581	arg1	F					583:583	PNGase F	576:583	PNGase F	576:583	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	8	58	theme	light	832:836	arg1	aggregometry					851:862	light transmission aggregometry	832:862	light transmission aggregometry	832:862	Platelet aggregation induced by ADP, arachidonic acid and collagen was detected through light transmission aggregometry, and platelet-leukocyte aggregates (PLAs) was detected by flow cytometry.
31188144	16	59	from	difference	1486:1495	arg1	binding					1504:1510	the binding	1500:1510	the binding of vWF and PLAs for PNGase F treated platelet	1500:1556	There is no difference in the binding of vWF and PLAs for PNGase F treated platelet.
31188144	1	60	theme	glycosylation	118:130	arg1	defects					132:138	glycosylation defects	118:138	: Platelet surface glycosylation defects	99:138	: Platelet surface glycosylation defects has been reported to be significantly associated with many diseases.
31188144	5	61	theme	platelet	461:468	arg1	acid					494:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	7	62	theme	von	684:686	arg1	factor					699:704	von Willebrand factor	684:704	von Willebrand factor (vWF)	684:710	The activation and platelet adhesion to von Willebrand factor (vWF) was measured by flow cytometry.
31188144	7	62	theme	von	684:686	arg1	vWF					707:709	vWF	707:709	vWF	707:709	The activation and platelet adhesion to von Willebrand factor (vWF) was measured by flow cytometry.
31188144	14	63	theme	F	1385:1385	arg1	treatment					1387:1395	PNGase F treatment	1378:1395	PNGase F treatment	1378:1395	Platelet surface sialic acid was increased after PNGase F treatment.
31188144	5	64	theme	surface	470:476	arg1	acid					494:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	0	65	theme	strong	63:68	arg1	impact					70:75	a strong impact	61:75	a strong impact	61:75	The platelet surface glycosylation caused by glycosidase has a strong impact on platelet function.
31188144	7	66	theme	Willebrand	688:697	arg1	factor					699:704	von Willebrand factor	684:704	von Willebrand factor (vWF)	684:710	The activation and platelet adhesion to von Willebrand factor (vWF) was measured by flow cytometry.
31188144	7	66	theme	Willebrand	688:697	arg1	vWF					707:709	vWF	707:709	vWF	707:709	The activation and platelet adhesion to von Willebrand factor (vWF) was measured by flow cytometry.
31188144	2	67	theme	surface	248:254	arg1	glycosylation					256:268	platelet surface glycosylation	239:268	platelet surface glycosylation	239:268	Our previous study found that platelet surface glycosylation is altered in coronary heart disease.
31188144	5	68	theme	N-linked	535:542	arg1	oligosaccharides					544:559	N-linked oligosaccharides	535:559	N-linked oligosaccharides	535:559	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	5	69	theme	terminal	478:485	arg1	acid					494:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid	457:497	The platelet surface terminal sialic acid was removed by neuraminidase A, and N-linked oligosaccharides was removed by PNGase F.
31188144	9	70	theme	Neuraminidase	938:950	arg1	treatment					954:962	Neuraminidase A treatment	938:962	Neuraminidase A treatment	938:962	Neuraminidase A treatment caused sialic acid level decrease and β-galactose level increase significantly on platelet surface.
31188144	2	71	theme	platelet	239:246	arg1	glycosylation					256:268	platelet surface glycosylation	239:268	platelet surface glycosylation	239:268	Our previous study found that platelet surface glycosylation is altered in coronary heart disease.
31188144	2	72	gly	glycosylation	256:268	arg1	disease					299:305	coronary heart disease	284:305	coronary heart disease	284:305	Our previous study found that platelet surface glycosylation is altered in coronary heart disease.
31188144	17	73	theme	thrombosis	1741:1750	arg1	risk					1733:1736	the increased risk	1719:1736	the increased risk of thrombosis	1719:1750	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	17	73	theme	thrombosis	1741:1750	arg1	reactivity					1704:1713	high platelet reactivity	1690:1713	high platelet reactivity	1690:1713	We demonstrated that asialoglycosylation enhances platelet binding to vWF and forming PLAs, suggest that it may be associated with high platelet reactivity and the increased risk of thrombosis.
31188144	8	74	theme	arachidonic	781:791	arg1	acid					793:796	arachidonic acid	781:796	arachidonic acid	781:796	Platelet aggregation induced by ADP, arachidonic acid and collagen was detected through light transmission aggregometry, and platelet-leukocyte aggregates (PLAs) was detected by flow cytometry.
30521110	0	0	theme	Suzuki	87:92	arg1	Polymerization					94:107	Suzuki Polymerization	87:107	Suzuki Polymerization	87:107	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	4	1	theme	resolution	679:688	arg1	TEM					690:692	high resolution TEM	674:692	high resolution TEM	674:692	Both 2D-COF films have large lateral size and their crystalline domains were visualized by high resolution TEM.
30521110	5	2	theme	breakthrough	751:762	arg1	work					764:767	our breakthrough work	747:767	our breakthrough work	747:767	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	5	3	theme	2D	812:813	arg1	films					830:834	various 2D conjugated COF films	804:834	various 2D conjugated COF films	804:834	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	6	4	theme	linked	948:953	arg1	films					962:966	-C=N- linked 2D COF films	942:966	-C=N- linked 2D COF films	942:966	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	5	theme	2D	955:956	arg1	films					962:966	-C=N- linked 2D COF films	942:966	-C=N- linked 2D COF films	942:966	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	6	theme	evolution	1011:1019	arg1	reaction					1021:1028	hydrogen evolution reaction	1002:1028	hydrogen evolution reaction	1002:1028	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	7	link	linked	948:953	arg1	films					962:966	-C=N- linked 2D COF films	942:966	-C=N- linked 2D COF films	942:966	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	8	with	comparable	1040:1049	arg1	graphene					1086:1093	nitrogen- or phosphorus-doped graphene	1056:1093	nitrogen- or phosphorus-doped graphene	1056:1093	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	9	theme	COF	958:960	arg1	films					962:966	-C=N- linked 2D COF films	942:966	-C=N- linked 2D COF films	942:966	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	0	10	from	Synthesis	0:8	arg1	Interface					128:136	a Liquid-Liquid Interface	112:136	a Liquid-Liquid Interface	112:136	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	3	11	theme	different	507:515	arg1	films					524:528	two different 2D-COF films	503:528	two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF	503:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	11	theme	different	507:515	arg1	2D-COF					575:580	a porphyrin-contained 2D-COF	553:580	a porphyrin-contained 2D-COF	553:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	11	theme	different	507:515	arg1	graphene					540:547	a porous graphene	531:547	a porous graphene	531:547	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	2	12	theme	simple	289:294	arg1	strategy					305:312	a very simple and mild strategy	282:312	a very simple and mild strategy	282:312	Now a very simple and mild strategy has been developed to synthesize them by Suzuki polymerization on a water-toluene interface in a refrigerator.
30521110	4	13	theme	2D-COF	588:593	arg1	films					595:599	Both 2D-COF films	583:599	Both 2D-COF films	583:599	Both 2D-COF films have large lateral size and their crystalline domains were visualized by high resolution TEM.
30521110	6	14	theme	application	841:851	arg1	studies					853:859	application studies	841:859	application studies	841:859	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	3	15	theme	porous	533:538	arg1	films					524:528	two different 2D-COF films	503:528	two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF	503:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	15	theme	porous	533:538	arg1	graphene					540:547	a porous graphene	531:547	a porous graphene	531:547	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	5	16	theme	COF	826:828	arg1	films					830:834	various 2D conjugated COF films	804:834	various 2D conjugated COF films	804:834	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	0	17	theme	Liquid-Liquid	114:126	arg1	Interface					128:136	a Liquid-Liquid Interface	112:136	a Liquid-Liquid Interface	112:136	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	3	18	dep	films	524:528	arg1	2D-COF					575:580	a porphyrin-contained 2D-COF	553:580	a porphyrin-contained 2D-COF	553:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	18	dep	films	524:528	arg1	films					524:528	two different 2D-COF films	503:528	two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF	503:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	18	dep	films	524:528	arg1	graphene					540:547	a porous graphene	531:547	a porous graphene	531:547	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	5	19	theme	conjugated	815:824	arg1	films					830:834	various 2D conjugated COF films	804:834	various 2D conjugated COF films	804:834	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	3	20	theme	films	524:528	arg1	synthesis					490:498	the successful synthesis	475:498	the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF	475:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	2	21	theme	water-toluene	382:394	arg1	interface					396:404	a water-toluene interface	380:404	a water-toluene interface in a refrigerator	380:422	Now a very simple and mild strategy has been developed to synthesize them by Suzuki polymerization on a water-toluene interface in a refrigerator.
30521110	5	22	theme	reaction	737:744	arg1	compatibility					713:725	the wide compatibility	704:725	the wide compatibility of Suzuki reaction	704:744	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	6	23	theme	nitrogen-	1056:1064	arg1	graphene					1086:1093	nitrogen- or phosphorus-doped graphene	1056:1093	nitrogen- or phosphorus-doped graphene	1056:1093	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	24	theme	hydrogen	1002:1009	arg1	reaction					1021:1028	hydrogen evolution reaction	1002:1028	hydrogen evolution reaction	1002:1028	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	1	25	theme	conjugated	187:196	arg1	films					231:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films	152:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds	152:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	6	26	theme	porous	866:871	arg1	graphene					873:880	the porous graphene	862:880	the porous graphene	862:880	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	1	27	theme	covalent	198:205	arg1	COF					226:228	COF	226:228	COF	226:228	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	1	27	theme	covalent	198:205	arg1	framework					215:223	covalent organic framework	198:223	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds	152:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	6	28	theme	catalytic	979:987	arg1	activity					989:996	a good catalytic activity	972:996	a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene	972:1093	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	29	theme	-C=N-	942:946	arg1	films					962:966	-C=N- linked 2D COF films	942:966	-C=N- linked 2D COF films	942:966	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	2	30	theme	mild	300:303	arg1	strategy					305:312	a very simple and mild strategy	282:312	a very simple and mild strategy	282:312	Now a very simple and mild strategy has been developed to synthesize them by Suzuki polymerization on a water-toluene interface in a refrigerator.
30521110	1	31	theme	organic	207:213	arg1	COF					226:228	COF	226:228	COF	226:228	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	1	31	theme	organic	207:213	arg1	framework					215:223	covalent organic framework	198:223	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds	152:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	0	32	theme	Bonded	17:22	arg1	Films					78:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	1	33	theme	framework	215:223	arg1	films					231:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films	152:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds	152:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	0	34	theme	C-C	13:15	arg1	Films					78:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	1	35	dep	two-dimensional	166:180	arg1	2D					183:184	2D	183:184	2D	183:184	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	6	36	theme	good	893:896	arg1	higher					930:935	higher	930:935	higher	930:935	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	36	theme	good	893:896	arg1	mobility					906:913	a good carrier mobility	891:913	a good carrier mobility	891:913	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	1	37	theme	free-standing	152:164	arg1	films					231:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films	152:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds	152:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	0	38	theme	Conjugated	40:49	arg1	Films					78:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	4	39	theme	crystalline	635:645	arg1	domains					647:653	their crystalline domains	629:653	their crystalline domains	629:653	Both 2D-COF films have large lateral size and their crystalline domains were visualized by high resolution TEM.
30521110	3	40	theme	porphyrin-contained	555:573	arg1	2D-COF					575:580	a porphyrin-contained 2D-COF	553:580	a porphyrin-contained 2D-COF	553:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	40	theme	porphyrin-contained	555:573	arg1	films					524:528	two different 2D-COF films	503:528	two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF	503:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	0	41	theme	Two-Dimensional	24:38	arg1	Films					78:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	5	42	theme	wide	708:711	arg1	compatibility					713:725	the wide compatibility	704:725	the wide compatibility of Suzuki reaction	704:744	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	5	43	theme	films	830:834	arg1	synthesis					791:799	the synthesis	787:799	the synthesis of various 2D conjugated COF films	787:834	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	3	44	theme	strategy	449:456	arg1	versatility					429:439	The versatility	425:439	The versatility of this strategy	425:456	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	0	45	theme	Organic	60:66	arg1	Films					78:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	2	46	from	polymerization	362:375	arg1	interface					396:404	a water-toluene interface	380:404	a water-toluene interface in a refrigerator	380:422	Now a very simple and mild strategy has been developed to synthesize them by Suzuki polymerization on a water-toluene interface in a refrigerator.
30521110	3	47	theme	successful	479:488	arg1	synthesis					490:498	the successful synthesis	475:498	the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF	475:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	0	48	theme	Covalent	51:58	arg1	Films					78:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	4	49	theme	high	674:677	arg1	TEM					690:692	high resolution TEM	674:692	high resolution TEM	674:692	Both 2D-COF films have large lateral size and their crystalline domains were visualized by high resolution TEM.
30521110	6	50	theme	phosphorus-doped	1069:1084	arg1	graphene					1086:1093	nitrogen- or phosphorus-doped graphene	1056:1093	nitrogen- or phosphorus-doped graphene	1056:1093	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	1	51	theme	films	231:235	arg1	Synthesis					139:147	Synthesis	139:147	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds	139:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	5	52	theme	various	804:810	arg1	films					830:834	various 2D conjugated COF films	804:834	various 2D conjugated COF films	804:834	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	3	53	theme	2D-COF	517:522	arg1	films					524:528	two different 2D-COF films	503:528	two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF	503:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	53	theme	2D-COF	517:522	arg1	2D-COF					575:580	a porphyrin-contained 2D-COF	553:580	a porphyrin-contained 2D-COF	553:580	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	3	53	theme	2D-COF	517:522	arg1	graphene					540:547	a porous graphene	531:547	a porous graphene	531:547	The versatility of this strategy was confirmed by the successful synthesis of two different 2D-COF films: a porous graphene and a porphyrin-contained 2D-COF.
30521110	6	54	theme	good	974:977	arg1	activity					989:996	a good catalytic activity	972:996	a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene	972:1093	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	0	55	theme	Films	78:82	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.	0:137	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	5	56	theme	Suzuki	730:735	arg1	reaction					737:744	Suzuki reaction	730:744	Suzuki reaction	730:744	Based on the wide compatibility of Suzuki reaction, our breakthrough work opened a door for the synthesis of various 2D conjugated COF films.
30521110	2	57	from	interface	396:404	arg1	refrigerator					411:422	a refrigerator	409:422	a refrigerator	409:422	Now a very simple and mild strategy has been developed to synthesize them by Suzuki polymerization on a water-toluene interface in a refrigerator.
30521110	2	58	theme	Suzuki	355:360	arg1	polymerization					362:375	Suzuki polymerization	355:375	Suzuki polymerization on a water-toluene interface in a refrigerator	355:422	Now a very simple and mild strategy has been developed to synthesize them by Suzuki polymerization on a water-toluene interface in a refrigerator.
30521110	4	59	theme	lateral	612:618	arg1	size					620:623	large lateral size	606:623	large lateral size	606:623	Both 2D-COF films have large lateral size and their crystalline domains were visualized by high resolution TEM.
30521110	0	60	theme	Framework	68:76	arg1	Films					78:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films	13:82	Synthesis of C-C Bonded Two-Dimensional Conjugated Covalent Organic Framework Films by Suzuki Polymerization on a Liquid-Liquid Interface.
30521110	6	61	theme	carrier	898:904	arg1	higher					930:935	higher	930:935	higher	930:935	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	6	61	theme	carrier	898:904	arg1	mobility					906:913	a good carrier mobility	891:913	a good carrier mobility	891:913	For application studies, the porous graphene exhibits a good carrier mobility, which is much higher than -C=N- linked 2D COF films and a good catalytic activity for hydrogen evolution reaction, which is comparable with nitrogen- or phosphorus-doped graphene.
30521110	4	62	theme	large	606:610	arg1	size					620:623	large lateral size	606:623	large lateral size	606:623	Both 2D-COF films have large lateral size and their crystalline domains were visualized by high resolution TEM.
30521110	1	63	theme	two-dimensional	166:180	arg1	films					231:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films	152:235	free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds	152:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30521110	1	64	theme	C-C	247:249	arg1	bonds					251:255	C-C bonds	247:255	C-C bonds	247:255	Synthesis of free-standing two-dimensional (2D) conjugated covalent organic framework (COF) films linked by C-C bonds is highly desirable.
30389294	4	0	theme	potency	1038:1044	arg1	profiles					1046:1053	better overall potency profiles	1023:1053	better overall potency profiles	1023:1053	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	1	theme	different	918:926	arg1	size					933:936	different ring size	918:936	different ring size	918:936	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	2	2	theme	unique	334:339	arg1	structures					370:379	unique tetracyclic bezonfuran-based structures	334:379	unique tetracyclic bezonfuran-based structures	334:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	0	3	theme	allosteric	68:77	arg1	inhibitors					79:88	palm site allosteric inhibitors	58:88	palm site allosteric inhibitors of HCV NS5B polymerase	58:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	3	4	link	N-linked	462:469	arg1	structures					536:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	1	5	theme	NS5B	138:141	arg1	polymerase					143:152	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	1	5	theme	NS5B	138:141	arg1	target					165:170	a prime target	157:170	a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection	157:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	2	6	theme	NS5B	298:301	arg1	inhibitors					318:327	Several novel and potent HCV NS5B non-nucleoside inhibitors	269:327	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures	269:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	0	7	theme	HCV	93:95	arg1	polymerase					102:111	HCV NS5B polymerase	93:111	HCV NS5B polymerase	93:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	3	8	theme	preclinical	712:722	arg1	species					731:737	the three preclinical animal species	702:737	the three preclinical animal species	702:737	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	4	9	theme	GT1a	883:886	arg1	variants					888:895	clinically relevant GT1a variants	863:895	clinically relevant GT1a variants	863:895	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	10	theme	related	802:808	arg1	structures					791:800	tetracyclic structures	779:800	tetracyclic structures related to pan genotypic potency profiles	779:842	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	11	theme	number	1006:1011	arg1	ring					1013:1016	six number ring	1002:1016	six number ring	1002:1016	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	12	theme	ring	928:931	arg1	size					933:936	different ring size	918:936	different ring size	918:936	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	13	theme	structures	791:800	arg1	importance					765:774	the importance	761:774	the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants	761:895	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	14	with	compounds	987:995	arg1	ring					1013:1016	six number ring	1002:1016	six number ring	1002:1016	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	2	15	theme	HCV	294:296	arg1	inhibitors					318:327	Several novel and potent HCV NS5B non-nucleoside inhibitors	269:327	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures	269:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	0	16	theme	polymerase	102:111	arg1	inhibitors					79:88	palm site allosteric inhibitors	58:88	palm site allosteric inhibitors of HCV NS5B polymerase	58:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	4	17	theme	pan	813:815	arg1	profiles					835:842	pan genotypic potency profiles	813:842	pan genotypic potency profiles	813:842	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	3	18	theme	compound	444:451	arg1	MK-8876					453:459	clinical developmental compound MK-8876	421:459	clinical developmental compound MK-8876	421:459	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	0	19	theme	NS5B	97:100	arg1	polymerase					102:111	HCV NS5B polymerase	93:111	HCV NS5B polymerase	93:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	4	20	theme	tetracyclic	779:789	arg1	structures					791:800	tetracyclic structures	779:800	tetracyclic structures related to pan genotypic potency profiles	779:842	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	21	theme	genotypic	817:825	arg1	profiles					835:842	pan genotypic potency profiles	813:842	pan genotypic potency profiles	813:842	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	22	theme	overall	1030:1036	arg1	profiles					1046:1053	better overall potency profiles	1023:1053	better overall potency profiles	1023:1053	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	23	theme	better	1023:1028	arg1	profiles					1046:1053	better overall potency profiles	1023:1053	better overall potency profiles	1023:1053	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	2	24	theme	potent	287:292	arg1	inhibitors					318:327	Several novel and potent HCV NS5B non-nucleoside inhibitors	269:327	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures	269:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	3	25	theme	clinical	421:428	arg1	MK-8876					453:459	clinical developmental compound MK-8876	421:459	clinical developmental compound MK-8876	421:459	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	1	26	theme	chronic	246:252	arg1	infection					258:266	chronic HCV infection	246:266	chronic HCV infection	246:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	3	27	theme	broad	558:562	arg1	profiles					595:602	broad spectrum anti-replicon potency profiles	558:602	broad spectrum anti-replicon potency profiles	558:602	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	1	28	theme	prime	159:163	arg1	polymerase					143:152	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	1	28	theme	prime	159:163	arg1	target					165:170	a prime target	157:170	a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection	157:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	1	29	theme	HCV	254:256	arg1	infection					258:266	chronic HCV infection	246:266	chronic HCV infection	246:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	4	30	theme	relevant	874:881	arg1	variants					888:895	clinically relevant GT1a variants	863:895	clinically relevant GT1a variants	863:895	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	2	31	theme	novel	277:281	arg1	inhibitors					318:327	Several novel and potent HCV NS5B non-nucleoside inhibitors	269:327	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures	269:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	3	32	dep	C-linked	495:502	arg1	compounds					505:513	compounds 3 and 4	505:521	compounds 3 and 4	505:521	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	1	33	theme	infection	258:266	arg1	treatment					233:241	the treatment	229:241	the treatment of chronic HCV infection	229:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	3	34	link	C-linked	495:502	arg1	structures					536:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	2	35	theme	Several	269:275	arg1	inhibitors					318:327	Several novel and potent HCV NS5B non-nucleoside inhibitors	269:327	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures	269:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	3	36	theme	excellent	633:641	arg1	bioavailability					648:662	excellent oral bioavailability	633:662	excellent oral bioavailability	633:662	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	0	37	theme	tetracyclic	31:41	arg1	benzofurans					43:53	novel tetracyclic benzofurans	25:53	novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase	25:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	2	38	theme	non-nucleoside	303:316	arg1	inhibitors					318:327	Several novel and potent HCV NS5B non-nucleoside inhibitors	269:327	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures	269:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	3	39	theme	potency	587:593	arg1	profiles					595:602	broad spectrum anti-replicon potency profiles	558:602	broad spectrum anti-replicon potency profiles	558:602	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	3	40	theme	developmental	430:442	arg1	MK-8876					453:459	clinical developmental compound MK-8876	421:459	clinical developmental compound MK-8876	421:459	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	0	41	theme	novel	25:29	arg1	benzofurans					43:53	novel tetracyclic benzofurans	25:53	novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase	25:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	2	42	with	inhibitors	318:327	arg1	structures					370:379	unique tetracyclic bezonfuran-based structures	334:379	unique tetracyclic bezonfuran-based structures	334:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	3	43	theme	N-linked	462:469	arg1	structures					536:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	4	44	theme	six	1002:1004	arg1	number					1006:1011	number	1006:1011	number	1006:1011	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	3	45	theme	oral	643:646	arg1	bioavailability					648:662	excellent oral bioavailability	633:662	excellent oral bioavailability	633:662	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	3	46	theme	spectrum	564:571	arg1	profiles					595:602	broad spectrum anti-replicon potency profiles	558:602	broad spectrum anti-replicon potency profiles	558:602	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	0	47	theme	benzofurans	43:53	arg1	evaluation					11:20	evaluation	11:20	evaluation	11:20	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	0	47	theme	benzofurans	43:53	arg1	Design					0:5	Design	0:5	Design	0:5	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	3	48	theme	anti-replicon	573:585	arg1	profiles					595:602	broad spectrum anti-replicon potency profiles	558:602	broad spectrum anti-replicon potency profiles	558:602	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	3	49	theme	C-linked	495:502	arg1	structures					536:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	1	50	theme	Hepatitis	114:122	arg1	HCV					133:135	HCV	133:135	HCV	133:135	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	1	50	theme	Hepatitis	114:122	arg1	virus					126:130	Hepatitis C virus	114:130	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	4	51	theme	in	956:957	arg1	evaluations					965:975	in vitro evaluations	956:975	in vitro evaluations	956:975	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	52	theme	potency	827:833	arg1	profiles					835:842	pan genotypic potency profiles	813:842	pan genotypic potency profiles	813:842	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	1	53	theme	C	124:124	arg1	HCV					133:135	HCV	133:135	HCV	133:135	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	1	53	theme	C	124:124	arg1	virus					126:130	Hepatitis C virus	114:130	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	3	54	theme	tetracyclic	524:534	arg1	structures					536:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures	462:545	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	4	55	dep	in	956:957	arg1	vitro					959:963	vitro	959:963	vitro	959:963	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	3	56	theme	pharmacokinetic	668:682	arg1	parameters					684:693	pharmacokinetic parameters	668:693	pharmacokinetic parameters	668:693	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	3	57	dep	N-linked	462:469	arg1	compounds					472:480	compounds 1 and 2	472:488	compounds 1 and 2	472:488	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	1	58	theme	virus	126:130	arg1	polymerase					143:152	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase	114:152	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	1	58	theme	virus	126:130	arg1	target					165:170	a prime target	157:170	a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection	157:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	1	59	theme	direct-acting	195:207	arg1	drugs					219:223	direct-acting antiviral drugs	195:223	direct-acting antiviral drugs for the treatment of chronic HCV infection	195:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	0	60	theme	site	63:66	arg1	inhibitors					79:88	palm site allosteric inhibitors	58:88	palm site allosteric inhibitors of HCV NS5B polymerase	58:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	2	61	theme	bezonfuran-based	353:368	arg1	structures					370:379	unique tetracyclic bezonfuran-based structures	334:379	unique tetracyclic bezonfuran-based structures	334:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	1	62	theme	antiviral	209:217	arg1	drugs					219:223	direct-acting antiviral drugs	195:223	direct-acting antiviral drugs for the treatment of chronic HCV infection	195:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30389294	0	63	theme	palm	58:61	arg1	inhibitors					79:88	palm site allosteric inhibitors	58:88	palm site allosteric inhibitors of HCV NS5B polymerase	58:111	Design and evaluation of novel tetracyclic benzofurans as palm site allosteric inhibitors of HCV NS5B polymerase.
30389294	3	64	theme	animal	724:729	arg1	species					731:737	the three preclinical animal species	702:737	the three preclinical animal species	702:737	Similar to clinical developmental compound MK-8876, N-linked (compounds 1 and 2) and C-linked (compounds 3 and 4) tetracyclic structures maintained broad spectrum anti-replicon potency profiles and demonstrated moderate to excellent oral bioavailability and pharmacokinetic parameters across the three preclinical animal species.
30389294	4	65	contain	have	1018:1021	arg2	profiles					1046:1053	better overall potency profiles	1023:1053	better overall potency profiles	1023:1053	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	4	65	contain	have	1018:1021	arg1	compounds					987:995	compounds	987:995	compounds with six number ring	987:1016	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	2	66	theme	tetracyclic	341:351	arg1	structures					370:379	unique tetracyclic bezonfuran-based structures	334:379	unique tetracyclic bezonfuran-based structures	334:379	Several novel and potent HCV NS5B non-nucleoside inhibitors with unique tetracyclic bezonfuran-based structures were prepared and evaluated.
30389294	4	67	with	teracycles	902:911	arg1	size					933:936	different ring size	918:936	different ring size	918:936	To better understand the importance of tetracyclic structures related to pan genotypic potency profiles especially against clinically relevant GT1a variants, the teracycles with different ring size were prepared and in vitro evaluations suggested compounds with six number ring have better overall potency profiles.
30389294	1	68	theme	drugs	219:223	arg1	development					180:190	the development	176:190	the development of direct-acting antiviral drugs for the treatment of chronic HCV infection	176:266	Hepatitis C virus (HCV) NS5B polymerase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection.
30309696	5	0	theme	small	710:714	arg1	siRNA					733:737	siRNA	733:737	siRNA	733:737	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	0	theme	small	710:714	arg1	RNA					728:730	small interfering RNA	710:730	small interfering RNA (siRNA)	710:738	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	1	1	theme	SIBLING	124:130	arg1	family					187:192	the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family	120:192	the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins	120:216	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	0	2	theme	cells	64:68	arg1	migration					31:39	migration	31:39	migration	31:39	Knockdown of DSPP inhibits the migration and invasion of glioma cells.
30309696	0	2	theme	cells	64:68	arg1	invasion					45:52	invasion	45:52	invasion	45:52	Knockdown of DSPP inhibits the migration and invasion of glioma cells.
30309696	7	3	theme	glioma	1086:1091	arg1	cells					1093:1097	glioma cells migration and invasion	1086:1120	glioma cells migration and invasion	1086:1120	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	7	3	theme	glioma	1086:1091	arg1	invasion					1113:1120	invasion	1113:1120	invasion	1113:1120	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	7	3	theme	glioma	1086:1091	arg1	migration					1099:1107	migration	1099:1107	migration	1099:1107	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	3	4	from	function	461:468	arg1	cells					494:498	human glioma cells	481:498	human glioma cells	481:498	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	1	5	gly	phosphoglycoproteins	197:216	arg1	phosphoglycoproteins					197:216	phosphoglycoproteins	197:216	phosphoglycoproteins	197:216	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	1	6	dep	SIBLING	124:130	arg1	glycoproteins					172:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	5	7	from	role	637:640	arg1	carcinogenesis					660:673	glioma carcinogenesis	653:673	glioma carcinogenesis	653:673	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	7	8	theme	DSPP	1072:1075	arg1	knockdown					1059:1067	knockdown	1059:1067	knockdown of DSPP	1059:1075	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	3	9	dep	expression	435:444	arg1	the					431:433	the	431:433	the	431:433	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	7	10	dep	cells	1093:1097	arg1	cells					1093:1097	glioma cells migration and invasion	1086:1120	glioma cells migration and invasion	1086:1120	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	7	10	dep	cells	1093:1097	arg1	invasion					1113:1120	invasion	1113:1120	invasion	1113:1120	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	7	10	dep	cells	1093:1097	arg1	migration					1099:1107	migration	1099:1107	migration	1099:1107	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	3	11	theme	human	481:485	arg1	cells					494:498	human glioma cells	481:498	human glioma cells	481:498	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	1	12	theme	ligand	156:161	arg1	glycoproteins					172:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	1	13	theme	Small	133:137	arg1	glycoproteins					172:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	5	14	theme	DSPP	691:694	arg1	expression					696:705	the DSPP expression	687:705	the DSPP expression	687:705	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	1	15	gly	glycoproteins	172:184	arg1	glycoproteins					172:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	3	16	theme	glioma	487:492	arg1	cells					494:498	human glioma cells	481:498	human glioma cells	481:498	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	1	17	theme	integrin-binding	139:154	arg1	glycoproteins					172:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	5	18	theme	interfering	716:726	arg1	siRNA					733:737	siRNA	733:737	siRNA	733:737	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	18	theme	interfering	716:726	arg1	RNA					728:730	small interfering RNA	710:730	small interfering RNA (siRNA)	710:738	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	6	19	from	activation	955:964	arg1	cells					1007:1011	glioma cells	1000:1011	glioma cells	1000:1011	Furthermore, we showed that DSPP down-regulation significantly decreased the activation of the AKT/mTOR/p70S6K pathway in glioma cells.
30309696	3	20	from	expression	435:444	arg1	cells					494:498	human glioma cells	481:498	human glioma cells	481:498	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	1	21	theme	Dentin	71:76	arg1	sialophosphoprotein					78:96	Dentin sialophosphoprotein	71:96	Dentin sialophosphoprotein (DSPP)	71:103	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	1	21	theme	Dentin	71:76	arg1	member					110:115	a member	108:115	a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins	108:216	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	1	21	theme	Dentin	71:76	arg1	DSPP					99:102	DSPP	99:102	DSPP	99:102	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	2	22	theme	pathogenic	346:355	arg1	process					357:363	the pathogenic process	342:363	the pathogenic process of glioma	342:373	However, whether DSPP participates in the pathogenic process of glioma remains unknown.
30309696	7	23	theme	targeting	1139:1147	arg1	DSPP					1149:1152	targeting DSPP	1139:1152	targeting DSPP	1139:1152	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	7	23	theme	targeting	1139:1147	arg1	strategy					1199:1206	a potentially effective therapeutic strategy	1163:1206	a potentially effective therapeutic strategy for treating glioma	1163:1226	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	1	24	theme	N-linked	163:170	arg1	glycoproteins					172:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	6	25	theme	DSPP	906:909	arg1	down-regulation					911:925	DSPP down-regulation	906:925	DSPP down-regulation	906:925	Furthermore, we showed that DSPP down-regulation significantly decreased the activation of the AKT/mTOR/p70S6K pathway in glioma cells.
30309696	6	26	theme	glioma	1000:1005	arg1	cells					1007:1011	glioma cells	1000:1011	glioma cells	1000:1011	Furthermore, we showed that DSPP down-regulation significantly decreased the activation of the AKT/mTOR/p70S6K pathway in glioma cells.
30309696	0	27	theme	DSPP	13:16	arg1	Knockdown					0:8	Knockdown	0:8	Knockdown of DSPP	0:16	Knockdown of DSPP inhibits the migration and invasion of glioma cells.
30309696	4	28	theme	Western	525:531	arg1	blot					533:536	Western blot	525:536	Western blot	525:536	We demonstrated through Western blot that DSPP is overexpressed in glioma tissues comparing to normal brain tissues.
30309696	5	29	theme	glioma	653:658	arg1	carcinogenesis					660:673	glioma carcinogenesis	653:673	glioma carcinogenesis	653:673	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	30	theme	glioma	824:829	arg1	cells					831:835	glioma cells	824:835	glioma cells	824:835	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	4	31	theme	brain	603:607	arg1	tissues					609:615	normal brain tissues	596:615	normal brain tissues	596:615	We demonstrated through Western blot that DSPP is overexpressed in glioma tissues comparing to normal brain tissues.
30309696	1	32	theme	family	187:192	arg1	sialophosphoprotein					78:96	Dentin sialophosphoprotein	71:96	Dentin sialophosphoprotein (DSPP)	71:103	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	1	32	theme	family	187:192	arg1	member					110:115	a member	108:115	a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins	108:216	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	6	33	theme	pathway	989:995	arg1	activation					955:964	the activation	951:964	the activation of the AKT/mTOR/p70S6K pathway in glioma cells	951:1011	Furthermore, we showed that DSPP down-regulation significantly decreased the activation of the AKT/mTOR/p70S6K pathway in glioma cells.
30309696	1	34	theme	variety	274:280	arg1	migration					259:267	the migration	255:267	the migration of a variety of solid tumor cells	255:301	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	2	35	theme	glioma	368:373	arg1	process					357:363	the pathogenic process	342:363	the pathogenic process of glioma	342:373	However, whether DSPP participates in the pathogenic process of glioma remains unknown.
30309696	0	36	dep	migration	31:39	arg1	the					27:29	the	27:29	the	27:29	Knockdown of DSPP inhibits the migration and invasion of glioma cells.
30309696	5	37	theme	critical	842:849	arg1	characteristics					851:865	the critical characteristics	838:865	the critical characteristics of glioma	838:875	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	37	theme	critical	842:849	arg1	migration					798:806	migration	798:806	migration	798:806	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	1	38	theme	solid	285:289	arg1	cells					297:301	solid tumor cells	285:301	solid tumor cells	285:301	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	7	39	theme	therapeutic	1187:1197	arg1	DSPP					1149:1152	targeting DSPP	1139:1152	targeting DSPP	1139:1152	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	7	39	theme	therapeutic	1187:1197	arg1	strategy					1199:1206	a potentially effective therapeutic strategy	1163:1206	a potentially effective therapeutic strategy for treating glioma	1163:1226	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	1	40	link	N-linked	163:170	arg1	glycoproteins					172:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Small integrin-binding ligand N-linked glycoproteins	133:184	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	3	41	theme	biological	450:459	arg1	function					461:468	biological function	450:468	biological function	450:468	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	1	42	theme	tumor	291:295	arg1	cells					297:301	solid tumor cells	285:301	solid tumor cells	285:301	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	1	43	theme	phosphoglycoproteins	197:216	arg1	family					187:192	the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family	120:192	the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins	120:216	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	5	44	theme	DSPP	645:648	arg1	role					637:640	the role	633:640	the role of DSPP in glioma carcinogenesis	633:673	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	45	theme	glioma	870:875	arg1	characteristics					851:865	the critical characteristics	838:865	the critical characteristics of glioma	838:875	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	45	theme	glioma	870:875	arg1	migration					798:806	migration	798:806	migration	798:806	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	46	dep	migration	798:806	arg1	the					794:796	the	794:796	the	794:796	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	6	47	theme	AKT/mTOR/p70S6K	973:987	arg1	pathway					989:995	the AKT/mTOR/p70S6K pathway	969:995	the AKT/mTOR/p70S6K pathway	969:995	Furthermore, we showed that DSPP down-regulation significantly decreased the activation of the AKT/mTOR/p70S6K pathway in glioma cells.
30309696	0	48	theme	glioma	57:62	arg1	cells					64:68	glioma cells	57:68	glioma cells	57:68	Knockdown of DSPP inhibits the migration and invasion of glioma cells.
30309696	4	49	theme	normal	596:601	arg1	tissues					609:615	normal brain tissues	596:615	normal brain tissues	596:615	We demonstrated through Western blot that DSPP is overexpressed in glioma tissues comparing to normal brain tissues.
30309696	3	50	theme	DSPP	473:476	arg1	expression					435:444	expression	435:444	expression	435:444	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	3	50	theme	DSPP	473:476	arg1	function					461:468	biological function	450:468	biological function	450:468	In this study, we aimed to investigate the expression and biological function of DSPP in human glioma cells.
30309696	7	51	theme	effective	1177:1185	arg1	DSPP					1149:1152	targeting DSPP	1139:1152	targeting DSPP	1139:1152	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	7	51	theme	effective	1177:1185	arg1	strategy					1199:1206	a potentially effective therapeutic strategy	1163:1206	a potentially effective therapeutic strategy for treating glioma	1163:1226	Taken together, these findings indicate that knockdown of DSPP inhibits glioma cells migration and invasion, suggesting that targeting DSPP might be a potentially effective therapeutic strategy for treating glioma.
30309696	1	52	theme	cells	297:301	arg1	cells					297:301	solid tumor cells	285:301	solid tumor cells	285:301	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	1	52	theme	cells	297:301	arg1	variety					274:280	a variety	272:280	a variety of solid tumor cells	272:301	Dentin sialophosphoprotein (DSPP) is a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins and has been proved to contribute to the migration of a variety of solid tumor cells.
30309696	5	53	theme	DSPP	755:758	arg1	silencing					760:768	DSPP silencing	755:768	DSPP silencing	755:768	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	54	theme	cells	831:835	arg1	characteristics					851:865	the critical characteristics	838:865	the critical characteristics of glioma	838:875	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	54	theme	cells	831:835	arg1	invasion					812:819	invasion	812:819	invasion	812:819	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	5	54	theme	cells	831:835	arg1	migration					798:806	migration	798:806	migration	798:806	To investigate the role of DSPP in glioma carcinogenesis, we reduced the DSPP expression by small interfering RNA (siRNA) and found that DSPP silencing significantly inhibited the migration and invasion of glioma cells, the critical characteristics of glioma.
30309696	4	55	theme	glioma	568:573	arg1	tissues					575:581	glioma tissues	568:581	glioma tissues comparing to normal brain tissues	568:615	We demonstrated through Western blot that DSPP is overexpressed in glioma tissues comparing to normal brain tissues.
29885096	1	0	link	N-linked	115:122	arg1	profiles					138:145	N-linked glycosylation profiles	115:145	N-linked glycosylation profiles	115:145	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	8	1	theme	effect	1565:1570	arg1	discovery					1537:1545	The discovery	1533:1545	The discovery of this leachable effect on the cell culture production process	1533:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	8	1	theme	effect	1565:1570	arg1	step					1628:1631	an essential step	1615:1631	an essential step in implementing appropriate process control	1615:1675	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	3	2	theme	galactosylation	633:647	arg1	level					649:653	the molecule's terminal galactosylation level	609:653	the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales	609:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	1	3	theme	achieving	229:237	arg1	consistency					239:249	achieving consistency	229:249	achieving consistency in the product-associated glycan attributes	229:293	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	1	3	theme	achieving	229:237	arg1	indicator					311:319	an important indicator	298:319	an important indicator that the manufacturing process is under control	298:367	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	6	4	theme	greater	1243:1249	arg1	degree					1251:1256	a greater degree	1241:1256	a greater degree of variability	1241:1271	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	4	5	from	investigations	727:740	arg1	Results					704:710	Results	704:710	Results from extensive investigations	704:740	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	7	6	theme	pilot	1499:1503	arg1	bioreactors					1520:1530	pilot and commercial bioreactors	1499:1530	bioreactors	1520:1530	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	1	7	theme	product-associated	258:275	arg1	attributes					284:293	the product-associated glycan attributes	254:293	the product-associated glycan attributes	254:293	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	1	8	dep	indicator	311:319	arg1	control					361:367	control	361:367	control	361:367	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	3	9	theme	6,000-L	674:680	arg1	scales					682:687	2-L, 100-L, and 6,000-L scales	658:687	2-L, 100-L, and 6,000-L scales	658:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	0	10	from	galactosylation	73:87	arg1	antibodies					103:112	monoclonal antibodies	92:112	monoclonal antibodies	92:112	Scale-dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies.
29885096	6	11	theme	galactosylation	1311:1325	arg1	levels					1292:1297	higher overall levels	1277:1297	higher overall levels of terminal galactosylation	1277:1325	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	6	11	theme	galactosylation	1311:1325	arg1	degree					1251:1256	a greater degree	1241:1256	a greater degree of variability	1241:1271	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	4	12	theme	stainless	797:805	arg1	components					813:822	the stainless steel components	793:822	the stainless steel components	793:822	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	7	13	theme	galactosylation	1455:1469	arg1	levels					1471:1476	comparable terminal galactosylation levels	1435:1476	comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors	1435:1530	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	1	14	from	consistency	239:249	arg1	attributes					284:293	the product-associated glycan attributes	254:293	the product-associated glycan attributes	254:293	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	8	15	theme	culture	1584:1590	arg1	process					1603:1609	the cell culture production process	1575:1609	the cell culture production process	1575:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	6	16	theme	overall	1284:1290	arg1	levels					1292:1297	higher overall levels	1277:1297	higher overall levels of terminal galactosylation	1277:1325	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	4	17	theme	manganese	769:777	arg1	leaching					779:786	manganese leaching	769:786	manganese leaching from the stainless steel components	769:822	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	8	18	from	effect	1565:1570	arg1	process					1603:1609	the cell culture production process	1575:1609	the cell culture production process	1575:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	1	19	theme	protein	196:202	arg1	products					216:223	mammalian-derived protein therapeutic products	178:223	mammalian-derived protein therapeutic products	178:223	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	0	20	theme	monoclonal	92:101	arg1	antibodies					103:112	monoclonal antibodies	92:112	monoclonal antibodies	92:112	Scale-dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies.
29885096	4	21	theme	exposed	863:869	arg1	area					879:882	exposed surface area	863:882	exposed surface area	863:882	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	3	22	theme	scale	524:528	arg1	up					530:531	subsequent scale up	513:531	subsequent scale up for pilot demonstration for a monoclonal antibody program	513:589	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	2	23	theme	target	396:401	arg1	profile					410:416	meeting target glycan profile	388:416	meeting target glycan profile	388:416	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	2	23	theme	target	396:401	arg1	criterion					430:438	a common criterion	421:438	a common criterion for ensuring product efficacy	421:468	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	2	24	theme	product	453:459	arg1	efficacy					461:468	product efficacy	453:468	product efficacy	453:468	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	0	25	theme	Scale-dependent	0:14	arg1	leaching					26:33	Scale-dependent manganese leaching	0:33	Scale-dependent manganese leaching from stainless steel	0:54	Scale-dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies.
29885096	1	26	theme	N-linked	115:122	arg1	profiles					138:145	N-linked glycosylation profiles	115:145	N-linked glycosylation profiles	115:145	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	8	27	theme	process	1661:1667	arg1	control					1669:1675	appropriate process control	1649:1675	appropriate process control	1649:1675	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	8	28	from	process	1603:1609	arg1	discovery					1537:1545	The discovery	1533:1545	The discovery of this leachable effect on the cell culture production process	1533:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	8	28	from	process	1603:1609	arg1	step					1628:1631	an essential step	1615:1631	an essential step in implementing appropriate process control	1615:1675	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	5	29	theme	low	1044:1046	arg1	level					1048:1052	this low level	1039:1052	this low level	1039:1052	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	6	30	theme	glass	1137:1141	arg1	setup					1154:1158	the 2-L glass bioreactor setup	1129:1158	the 2-L glass bioreactor setup	1129:1158	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	3	31	theme	process	489:495	arg1	development					497:507	laboratory process development	478:507	laboratory process development	478:507	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	1	32	link	mammalian-derived	178:194	arg1	products					216:223	mammalian-derived protein therapeutic products	178:223	mammalian-derived protein therapeutic products	178:223	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	6	33	theme	2-L	1133:1135	arg1	setup					1154:1158	the 2-L glass bioreactor setup	1129:1158	the 2-L glass bioreactor setup	1129:1158	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	0	34	theme	stainless	40:48	arg1	steel					50:54	stainless steel	40:54	stainless steel	40:54	Scale-dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies.
29885096	3	35	theme	antibody	574:581	arg1	program					583:589	a monoclonal antibody program	561:589	a monoclonal antibody program	561:589	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	7	36	theme	steel	1380:1384	arg1	exposure					1394:1401	stainless steel surface exposure	1370:1401	stainless steel surface exposure to the cell culture	1370:1421	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	6	37	theme	higher	1277:1282	arg1	levels					1292:1297	higher overall levels	1277:1297	higher overall levels of terminal galactosylation	1277:1325	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	2	38	theme	glycan	403:408	arg1	profile					410:416	meeting target glycan profile	388:416	meeting target glycan profile	388:416	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	2	38	theme	glycan	403:408	arg1	criterion					430:438	a common criterion	421:438	a common criterion for ensuring product efficacy	421:468	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	6	39	theme	stainless	1204:1212	arg1	steel					1214:1218	stainless steel	1204:1218	stainless steel	1204:1218	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	10	40	theme	Chemical	1779:1786	arg1	Engineers					1788:1796	Chemical Engineers	1779:1796	Chemical Engineers	1779:1796	Prog., 2018 © 2018 American Institute of Chemical Engineers Biotechnol.
29885096	4	41	theme	cultivation	888:898	arg1	time					900:903	cultivation time	888:903	cultivation time	888:903	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	1	42	theme	important	301:309	arg1	consistency					239:249	achieving consistency	229:249	achieving consistency in the product-associated glycan attributes	229:293	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	1	42	theme	important	301:309	arg1	indicator					311:319	an important indicator	298:319	an important indicator that the manufacturing process is under control	298:367	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	5	43	theme	glycosylation	1091:1103	arg1	profiles					1105:1112	the protein glycosylation profiles	1079:1112	the protein glycosylation profiles	1079:1112	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	6	44	theme	exposure	1192:1199	arg1	exposure					1192:1199	exposure	1192:1199	exposure to stainless steel	1192:1218	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	6	44	theme	exposure	1192:1199	arg1	amount					1182:1187	the highest amount	1170:1187	the highest amount of exposure to stainless steel	1170:1218	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	2	45	theme	common	423:428	arg1	profile					410:416	meeting target glycan profile	388:416	meeting target glycan profile	388:416	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	2	45	theme	common	423:428	arg1	criterion					430:438	a common criterion	421:438	a common criterion for ensuring product efficacy	421:468	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	11	46	dep	2018	1831:1834	arg1	Prog.					1810:1814	Prog.	1810:1814	Prog.	1810:1814	Prog., 34:1290-1297, 2018.
29885096	3	47	from	discrepancies	592:604	arg1	level					649:653	the molecule's terminal galactosylation level	609:653	the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales	609:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	3	47	from	discrepancies	592:604	arg1	scales					682:687	2-L, 100-L, and 6,000-L scales	658:687	2-L, 100-L, and 6,000-L scales	658:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	3	48	theme	terminal	624:631	arg1	level					649:653	the molecule's terminal galactosylation level	609:653	the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales	609:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	1	49	theme	manufacturing	330:342	arg1	process					344:350	the manufacturing process	326:350	the manufacturing process	326:350	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	2	50	theme	meeting	388:394	arg1	profile					410:416	meeting target glycan profile	388:416	meeting target glycan profile	388:416	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	2	50	theme	meeting	388:394	arg1	criterion					430:438	a common criterion	421:438	a common criterion for ensuring product efficacy	421:468	More importantly, meeting target glycan profile is a common criterion for ensuring product efficacy.
29885096	6	51	theme	variability	1261:1271	arg1	levels					1292:1297	higher overall levels	1277:1297	higher overall levels of terminal galactosylation	1277:1325	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	6	51	theme	variability	1261:1271	arg1	degree					1251:1256	a greater degree	1241:1256	a greater degree of variability	1241:1271	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	3	52	theme	2-L	658:660	arg1	scales					682:687	2-L, 100-L, and 6,000-L scales	658:687	2-L, 100-L, and 6,000-L scales	658:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	5	53	theme	nanomolar	954:962	arg1	concentrations					964:977	nanomolar concentrations	954:977	nanomolar concentrations	954:977	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	4	54	theme	root	755:758	arg1	cause					760:764	the root cause	751:764	the root cause as manganese leaching from the stainless steel components	751:822	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	8	55	from	discovery	1537:1545	arg1	process					1603:1609	the cell culture production process	1575:1609	the cell culture production process	1575:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	5	56	theme	metal	920:924	arg1	impurity					926:933	this metal impurity	915:933	this metal impurity	915:933	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	8	57	theme	leachable	1555:1563	arg1	effect					1565:1570	this leachable effect	1550:1570	this leachable effect on the cell culture production process	1550:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	5	58	located	present	943:949	arg2	impurity					926:933	this metal impurity	915:933	this metal impurity	915:933	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	5	58	located	present	943:949	arg1	concentrations					964:977	nanomolar concentrations	954:977	nanomolar concentrations	954:977	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	1	59	theme	glycan	277:282	arg1	attributes					284:293	the product-associated glycan attributes	254:293	the product-associated glycan attributes	254:293	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	4	60	theme	extensive	717:725	arg1	investigations					727:740	extensive investigations	717:740	extensive investigations	717:740	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	3	61	theme	100-L	663:667	arg1	scales					682:687	2-L, 100-L, and 6,000-L scales	658:687	2-L, 100-L, and 6,000-L scales	658:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	8	62	theme	cell	1579:1582	arg1	process					1603:1609	the cell culture production process	1575:1609	the cell culture production process	1575:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	6	63	theme	terminal	1302:1309	arg1	galactosylation					1311:1325	terminal galactosylation	1302:1325	terminal galactosylation	1302:1325	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	7	64	theme	vessels	1350:1356	arg1	use					1332:1334	The use	1328:1334	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture	1328:1421	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	5	65	theme	spike-in	1006:1013	arg1	study					1015:1019	a spike-in study	1004:1019	a spike-in study	1004:1019	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	8	66	theme	production	1592:1601	arg1	process					1603:1609	the cell culture production process	1575:1609	the cell culture production process	1575:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	4	67	theme	steel	807:811	arg1	components					813:822	the stainless steel components	793:822	the stainless steel components	793:822	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	5	68	from	concentrations	964:977	arg1	present					943:949	present	943:949	present	943:949	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	1	69	theme	mammalian-derived	178:194	arg1	products					216:223	mammalian-derived protein therapeutic products	178:223	mammalian-derived protein therapeutic products	178:223	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	7	70	theme	terminal	1446:1453	arg1	levels					1471:1476	comparable terminal galactosylation levels	1435:1476	comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors	1435:1530	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	1	71	theme	therapeutic	204:214	arg1	products					216:223	mammalian-derived protein therapeutic products	178:223	mammalian-derived protein therapeutic products	178:223	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	8	72	theme	essential	1618:1626	arg1	discovery					1537:1545	The discovery	1533:1545	The discovery of this leachable effect on the cell culture production process	1533:1609	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	8	72	theme	essential	1618:1626	arg1	step					1628:1631	an essential step	1615:1631	an essential step in implementing appropriate process control	1615:1675	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	3	73	from	scales	682:687	arg1	discrepancies					592:604	discrepancies	592:604	discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales	592:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	3	73	from	scales	682:687	arg1	level					649:653	the molecule's terminal galactosylation level	609:653	the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales	609:687	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	7	74	theme	commercial	1509:1518	arg1	bioreactors					1520:1530	pilot and commercial bioreactors	1499:1530	bioreactors	1520:1530	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	7	75	theme	comparable	1435:1444	arg1	levels					1471:1476	comparable terminal galactosylation levels	1435:1476	comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors	1435:1530	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	6	76	theme	highest	1174:1180	arg1	exposure					1192:1199	exposure	1192:1199	exposure to stainless steel	1192:1218	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	6	76	theme	highest	1174:1180	arg1	amount					1182:1187	the highest amount	1170:1187	the highest amount of exposure to stainless steel	1170:1218	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	0	77	from	steel	50:54	arg1	leaching					26:33	Scale-dependent manganese leaching	0:33	Scale-dependent manganese leaching from stainless steel	0:54	Scale-dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies.
29885096	0	78	theme	manganese	16:24	arg1	leaching					26:33	Scale-dependent manganese leaching	0:33	Scale-dependent manganese leaching from stainless steel	0:54	Scale-dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies.
29885096	7	79	theme	cell	1410:1413	arg1	culture					1415:1421	the cell culture	1406:1421	the cell culture	1406:1421	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	3	80	theme	subsequent	513:522	arg1	up					530:531	subsequent scale up	513:531	subsequent scale up for pilot demonstration for a monoclonal antibody program	513:589	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	1	81	theme	glycosylation	124:136	arg1	profiles					138:145	N-linked glycosylation profiles	115:145	N-linked glycosylation profiles	115:145	N-linked glycosylation profiles are routinely characterized on mammalian-derived protein therapeutic products and achieving consistency in the product-associated glycan attributes is an important indicator that the manufacturing process is under control.
29885096	6	82	theme	bioreactor	1143:1152	arg1	setup					1154:1158	the 2-L glass bioreactor setup	1129:1158	the 2-L glass bioreactor setup	1129:1158	Surprisingly, the 2-L glass bioreactor setup exhibited the highest amount of exposure to stainless steel and resulted in both a greater degree of variability and higher overall levels of terminal galactosylation.
29885096	5	83	attach	present	943:949	arg2	impurity					926:933	this metal impurity	915:933	this metal impurity	915:933	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	5	83	attach	present	943:949	arg1	concentrations					964:977	nanomolar concentrations	954:977	nanomolar concentrations	954:977	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	9	84	theme	Chemical	1707:1714	arg1	Engineers					1716:1724	Chemical Engineers	1707:1724	Chemical Engineers	1707:1724	© 2018 American Institute of Chemical Engineers Biotechnol.
29885096	7	85	theme	surface	1386:1392	arg1	exposure					1394:1401	stainless steel surface exposure	1370:1401	stainless steel surface exposure to the cell culture	1370:1421	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	3	86	theme	pilot	537:541	arg1	demonstration					543:555	pilot demonstration	537:555	pilot demonstration	537:555	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	0	87	theme	terminal	64:71	arg1	galactosylation					73:87	terminal galactosylation	64:87	terminal galactosylation in monoclonal antibodies	64:112	Scale-dependent manganese leaching from stainless steel impacts terminal galactosylation in monoclonal antibodies.
29885096	8	88	theme	appropriate	1649:1659	arg1	control					1669:1675	appropriate process control	1649:1675	appropriate process control	1649:1675	The discovery of this leachable effect on the cell culture production process was an essential step in implementing appropriate process control.
29885096	7	89	theme	stainless	1370:1378	arg1	exposure					1394:1401	stainless steel surface exposure	1370:1401	stainless steel surface exposure to the cell culture	1370:1421	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29885096	3	90	theme	laboratory	478:487	arg1	development					497:507	laboratory process development	478:507	laboratory process development	478:507	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	4	91	from	components	813:822	arg1	leaching					779:786	manganese leaching	769:786	manganese leaching from the stainless steel components	769:822	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	4	92	theme	surface	871:877	arg1	area					879:882	exposed surface area	863:882	exposed surface area	863:882	Results from extensive investigations revealed the root cause as manganese leaching from the stainless steel components and that this leaching is dependent on exposed surface area and cultivation time.
29885096	3	93	theme	monoclonal	563:572	arg1	program					583:589	a monoclonal antibody program	561:589	a monoclonal antibody program	561:589	During laboratory process development and subsequent scale up for pilot demonstration for a monoclonal antibody program, discrepancies in the molecule's terminal galactosylation level at 2-L, 100-L, and 6,000-L scales were observed.
29885096	5	94	theme	protein	1083:1089	arg1	profiles					1105:1112	the protein glycosylation profiles	1079:1112	the protein glycosylation profiles	1079:1112	Although this metal impurity is only present at nanomolar concentrations and difficult to detect, a spike-in study demonstrated that this low level was sufficient to impact the protein glycosylation profiles.
29885096	7	95	theme	disposable	1339:1348	arg1	vessels					1350:1356	disposable vessels	1339:1356	disposable vessels	1339:1356	The use of disposable vessels to minimize stainless steel surface exposure to the cell culture resulted in comparable terminal galactosylation levels to those measured in pilot and commercial bioreactors.
29749234	4	0	theme	DFT	1020:1022	arg1	calculations					1032:1043	DFT (B3LYP) calculations	1020:1043	DFT (B3LYP) calculations	1020:1043	The proposed structure was supported by DFT (B3LYP) calculations.
29749234	3	1	theme	complexes	724:732	arg1	states					710:715	the high-valent Cu(III) states	686:715	the high-valent Cu(III) states of the complexes	686:732	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	6	2	theme	organometallic	1430:1443	arg1	reactions					1445:1453	their organometallic reactions	1424:1453	their organometallic reactions	1424:1453	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	3	3	theme	copper	940:945	arg1	complexes					951:959	regular corrole copper(II) complexes	924:959	regular corrole copper(II) complexes with an NNNN core	924:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	1	4	theme	carbacorrole-based	209:226	arg1	ligands					253:259	carbacorrole-based tetradentate macrocyclic ligands	209:259	carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	209:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	3	5	theme	states	710:715	arg1	stability					673:681	The remarkable stability	658:681	The remarkable stability of the high-valent Cu(III) states of the complexes	658:732	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	6	6	theme	organometallic	1285:1298	arg1	complexes					1308:1316	these organometallic corrole complexes	1279:1316	these organometallic corrole complexes	1279:1316	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	6	7	theme	corrole	1300:1306	arg1	complexes					1308:1316	these organometallic corrole complexes	1279:1316	these organometallic corrole complexes	1279:1316	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	1	8	theme	tetradentate	228:239	arg1	ligands					253:259	carbacorrole-based tetradentate macrocyclic ligands	209:259	carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	209:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	5	9	theme	CuNCC4	1173:1178	arg1	oxidation					1160:1168	the one-electron oxidation	1143:1168	the one-electron oxidation of CuNCC4	1143:1178	Furthermore, a π-laminated dimer architecture linked through the inner carbons was obtained from the one-electron oxidation of CuNCC4.
29749234	3	10	theme	regular	924:930	arg1	complexes					951:959	regular corrole copper(II) complexes	924:959	regular corrole copper(II) complexes with an NNNN core	924:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	1	11	theme	macrocyclic	241:251	arg1	ligands					253:259	carbacorrole-based tetradentate macrocyclic ligands	209:259	carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	209:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	2	12	theme	organocopper	631:642	arg1	complexes					583:591	these organocopper complexes	564:591	these organocopper complexes	564:591	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	2	12	theme	organocopper	631:642	arg1	species					649:655	novel organocopper(III) species	625:655	novel organocopper(III) species	625:655	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	0	13	theme	Redox	102:106	arg1	Reactivity					108:117	Redox Reactivity	102:117	Redox Reactivity	102:117	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	0	13	theme	Redox	102:106	arg1	Corroles					59:66	N-Confused/N-Linked Corroles	39:66	N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity	39:117	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	1	14	theme	spectroscopic	348:360	arg1	analysis					401:408	X-ray crystallographic analysis	378:408	X-ray crystallographic analysis	378:408	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	14	theme	spectroscopic	348:360	arg1	means					362:366	spectroscopic means	348:366	spectroscopic means including X-ray crystallographic analysis	348:408	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	6	15	theme	complexes	1308:1316	arg1	energies					1248:1255	molecular orbital energies	1230:1255	molecular orbital energies	1230:1255	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	6	15	theme	complexes	1308:1316	arg1	profiles					1267:1274	redox profiles	1261:1274	redox profiles	1261:1274	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	6	16	theme	precise	1202:1208	arg1	manipulation					1210:1221	the precise manipulation	1198:1221	the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes	1198:1316	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	3	17	theme	complexes	951:959	arg1	nature					914:919	the redox-noninnocent radical nature	884:919	the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core	884:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	6	18	theme	orbital	1240:1246	arg1	energies					1248:1255	molecular orbital energies	1230:1255	molecular orbital energies	1230:1255	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	2	19	theme	diamagnetic	544:554	arg1	nature					556:561	temperature-independent diamagnetic nature	520:561	temperature-independent diamagnetic nature	520:561	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	4	20	theme	B3LYP	1025:1029	arg1	calculations					1032:1043	DFT (B3LYP) calculations	1020:1043	DFT (B3LYP) calculations	1020:1043	The proposed structure was supported by DFT (B3LYP) calculations.
29749234	0	21	theme	Ground-State	0:11	arg1	Copper					13:18	Ground-State Copper(III)	0:23	Ground-State Copper(III)	0:23	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	2	22	dep	structures	449:458	arg1	the					414:416	the	414:416	the	414:416	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	2	22	dep	structures	449:458	arg1	basis					418:422	basis	418:422	basis	418:422	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	3	23	theme	II	947:948	arg1	complexes					951:959	regular corrole copper(II) complexes	924:959	regular corrole copper(II) complexes with an NNNN core	924:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	2	24	theme	planar	442:447	arg1	structures					449:458	their distinct planar structures	427:458	their distinct planar structures	427:458	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	3	25	theme	NNNN	969:972	arg1	core					974:977	an NNNN core	966:977	an NNNN core	966:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	3	26	theme	high-valent	690:700	arg1	states					710:715	the high-valent Cu(III) states	686:715	the high-valent Cu(III) states of the complexes	686:732	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	2	27	theme	distinct	433:440	arg1	structures					449:458	their distinct planar structures	427:458	their distinct planar structures	427:458	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	1	28	theme	NNNC	266:269	arg1	cores					284:288	NNNC coordination cores	266:288	NNNC coordination cores	266:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	6	29	theme	species	1393:1399	arg1	development					1409:1419	the development	1405:1419	the development of their organometallic reactions	1405:1453	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	6	29	theme	species	1393:1399	arg1	isolation					1347:1355	the isolation	1343:1355	the isolation of yet unexplored high-valent metal species	1343:1399	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	1	30	theme	coordination	271:282	arg1	cores					284:288	NNNC coordination cores	266:288	NNNC coordination cores	266:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	6	31	theme	metal	1387:1391	arg1	species					1393:1399	yet unexplored high-valent metal species	1360:1399	yet unexplored high-valent metal species	1360:1399	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	1	32	theme	X-ray	378:382	arg1	analysis					401:408	X-ray crystallographic analysis	378:408	X-ray crystallographic analysis	378:408	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	0	33	dep	Corroles	59:66	arg1	Synthesis					69:77	Synthesis	69:77	Synthesis	69:77	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	0	33	dep	Corroles	59:66	arg1	Reactivity					108:117	Redox Reactivity	102:117	Redox Reactivity	102:117	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	0	33	dep	Corroles	59:66	arg1	Corroles					59:66	N-Confused/N-Linked Corroles	39:66	N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity	39:117	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	0	33	dep	Corroles	59:66	arg1	Characterization					80:95	Characterization	80:95	Characterization	80:95	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	2	34	theme	spectroscopic	492:504	arg1	features					506:513	X-ray absorption/photoelectron spectroscopic features	461:513	X-ray absorption/photoelectron spectroscopic features	461:513	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	6	35	theme	high-valent	1375:1385	arg1	species					1393:1399	yet unexplored high-valent metal species	1360:1399	yet unexplored high-valent metal species	1360:1399	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	1	36	theme	crystallographic	384:399	arg1	analysis					401:408	X-ray crystallographic analysis	378:408	X-ray crystallographic analysis	378:408	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	2	37	theme	absorption/photoelectron	467:490	arg1	features					506:513	X-ray absorption/photoelectron spectroscopic features	461:513	X-ray absorption/photoelectron spectroscopic features	461:513	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	3	38	theme	NNNC	809:812	arg1	coordination					814:825	the peculiar NNNC coordination	796:825	the peculiar NNNC coordination	796:825	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	2	39	theme	organocopper	570:581	arg1	complexes					583:591	these organocopper complexes	564:591	these organocopper complexes	564:591	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	2	39	theme	organocopper	570:581	arg1	species					649:655	novel organocopper(III) species	625:655	novel organocopper(III) species	625:655	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	5	40	theme	inner	1111:1115	arg1	carbons					1117:1123	the inner carbons	1107:1123	the inner carbons	1107:1123	Furthermore, a π-laminated dimer architecture linked through the inner carbons was obtained from the one-electron oxidation of CuNCC4.
29749234	6	41	theme	profiles	1267:1274	arg1	manipulation					1210:1221	the precise manipulation	1198:1221	the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes	1198:1316	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	4	42	theme	proposed	984:991	arg1	structure					993:1001	The proposed structure	980:1001	The proposed structure	980:1001	The proposed structure was supported by DFT (B3LYP) calculations.
29749234	2	43	theme	X-ray	461:465	arg1	features					506:513	X-ray absorption/photoelectron spectroscopic features	461:513	X-ray absorption/photoelectron spectroscopic features	461:513	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	2	44	theme	novel	625:629	arg1	complexes					583:591	these organocopper complexes	564:591	these organocopper complexes	564:591	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	2	44	theme	novel	625:629	arg1	species					649:655	novel organocopper(III) species	625:655	novel organocopper(III) species	625:655	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	6	45	theme	reactions	1445:1453	arg1	development					1409:1419	the development	1405:1419	the development of their organometallic reactions	1405:1453	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	6	45	theme	reactions	1445:1453	arg1	isolation					1347:1355	the isolation	1343:1355	the isolation of yet unexplored high-valent metal species	1343:1399	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	6	46	theme	redox	1261:1265	arg1	profiles					1267:1274	redox profiles	1261:1274	redox profiles	1261:1274	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	1	47	with	ligands	253:259	arg1	cores					284:288	NNNC coordination cores	266:288	NNNC coordination cores	266:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	6	48	theme	unexplored	1364:1373	arg1	species					1393:1399	yet unexplored high-valent metal species	1360:1399	yet unexplored high-valent metal species	1360:1399	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	3	49	attach	derived	783:789	arg2	structure					773:781	the closed-shell electronic structure	745:781	the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core	745:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	3	49	attach	derived	783:789	arg1	coordination					814:825	the peculiar NNNC coordination	796:825	the peculiar NNNC coordination	796:825	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	5	50	theme	π-laminated	1061:1071	arg1	architecture					1079:1090	a π-laminated dimer architecture	1059:1090	a π-laminated dimer architecture linked through the inner carbons	1059:1123	Furthermore, a π-laminated dimer architecture linked through the inner carbons was obtained from the one-electron oxidation of CuNCC4.
29749234	1	51	dep	complexes	159:167	arg1	CuNCC4					178:183	CuNCC4	178:183	CuNCC4	178:183	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	51	dep	complexes	159:167	arg1	CuBN					190:193	CuBN	190:193	CuBN	190:193	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	51	dep	complexes	159:167	arg1	CuNCC2					170:175	CuNCC2	170:175	CuNCC2	170:175	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	51	dep	complexes	159:167	arg1	complexes					159:167	Stable square planar organocopper(III) complexes	120:167	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	120:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	3	52	theme	radical	906:912	arg1	nature					914:919	the redox-noninnocent radical nature	884:919	the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core	884:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	3	53	theme	peculiar	800:807	arg1	coordination					814:825	the peculiar NNNC coordination	796:825	the peculiar NNNC coordination	796:825	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	3	54	theme	closed-shell	749:760	arg1	structure					773:781	the closed-shell electronic structure	745:781	the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core	745:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	5	55	theme	dimer	1073:1077	arg1	architecture					1079:1090	a π-laminated dimer architecture	1059:1090	a π-laminated dimer architecture linked through the inner carbons	1059:1123	Furthermore, a π-laminated dimer architecture linked through the inner carbons was obtained from the one-electron oxidation of CuNCC4.
29749234	6	56	theme	energies	1248:1255	arg1	manipulation					1210:1221	the precise manipulation	1198:1221	the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes	1198:1316	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	6	57	dep	energies	1248:1255	arg1	the					1226:1228	the	1226:1228	the	1226:1228	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	1	58	theme	Stable	120:125	arg1	CuNCC4					178:183	CuNCC4	178:183	CuNCC4	178:183	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	58	theme	Stable	120:125	arg1	CuBN					190:193	CuBN	190:193	CuBN	190:193	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	58	theme	Stable	120:125	arg1	CuNCC2					170:175	CuNCC2	170:175	CuNCC2	170:175	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	58	theme	Stable	120:125	arg1	complexes					159:167	Stable square planar organocopper(III) complexes	120:167	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	120:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	3	59	theme	corrole-modified	834:849	arg1	frameworks					851:860	the corrole-modified frameworks	830:860	the corrole-modified frameworks	830:860	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	3	60	theme	Cu	702:703	arg1	states					710:715	the high-valent Cu(III) states	686:715	the high-valent Cu(III) states of the complexes	686:732	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	3	61	theme	remarkable	662:671	arg1	stability					673:681	The remarkable stability	658:681	The remarkable stability of the high-valent Cu(III) states of the complexes	658:732	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	1	62	theme	square	127:132	arg1	CuNCC4					178:183	CuNCC4	178:183	CuNCC4	178:183	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	62	theme	square	127:132	arg1	CuBN					190:193	CuBN	190:193	CuBN	190:193	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	62	theme	square	127:132	arg1	CuNCC2					170:175	CuNCC2	170:175	CuNCC2	170:175	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	62	theme	square	127:132	arg1	complexes					159:167	Stable square planar organocopper(III) complexes	120:167	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	120:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	3	63	theme	electronic	762:771	arg1	structure					773:781	the closed-shell electronic structure	745:781	the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core	745:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	3	64	theme	frameworks	851:860	arg1	coordination					814:825	the peculiar NNNC coordination	796:825	the peculiar NNNC coordination	796:825	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	2	65	theme	temperature-independent	520:542	arg1	nature					556:561	temperature-independent diamagnetic nature	520:561	temperature-independent diamagnetic nature	520:561	On the basis of their distinct planar structures, X-ray absorption/photoelectron spectroscopic features, and temperature-independent diamagnetic nature, these organocopper complexes can be preferably considered as novel organocopper(III) species.
29749234	3	66	with	complexes	951:959	arg1	core					974:977	an NNNN core	966:977	an NNNN core	966:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	6	67	theme	molecular	1230:1238	arg1	energies					1248:1255	molecular orbital energies	1230:1255	molecular orbital energies	1230:1255	We envisage that the precise manipulation of the molecular orbital energies and redox profiles of these organometallic corrole complexes could eventually lead to the isolation of yet unexplored high-valent metal species and the development of their organometallic reactions.
29749234	1	68	theme	planar	134:139	arg1	CuNCC4					178:183	CuNCC4	178:183	CuNCC4	178:183	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	68	theme	planar	134:139	arg1	CuBN					190:193	CuBN	190:193	CuBN	190:193	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	68	theme	planar	134:139	arg1	CuNCC2					170:175	CuNCC2	170:175	CuNCC2	170:175	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	68	theme	planar	134:139	arg1	complexes					159:167	Stable square planar organocopper(III) complexes	120:167	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	120:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	3	69	theme	redox-noninnocent	888:904	arg1	nature					914:919	the redox-noninnocent radical nature	884:919	the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core	884:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29749234	0	70	theme	N-Confused/N-Linked	39:57	arg1	Synthesis					69:77	Synthesis	69:77	Synthesis	69:77	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	0	70	theme	N-Confused/N-Linked	39:57	arg1	Corroles					59:66	N-Confused/N-Linked Corroles	39:66	N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity	39:117	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	0	70	theme	N-Confused/N-Linked	39:57	arg1	Reactivity					108:117	Redox Reactivity	102:117	Redox Reactivity	102:117	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	0	70	theme	N-Confused/N-Linked	39:57	arg1	Characterization					80:95	Characterization	80:95	Characterization	80:95	Ground-State Copper(III) Stabilized by N-Confused/N-Linked Corroles: Synthesis, Characterization, and Redox Reactivity.
29749234	5	71	theme	one-electron	1147:1158	arg1	oxidation					1160:1168	the one-electron oxidation	1143:1168	the one-electron oxidation of CuNCC4	1143:1178	Furthermore, a π-laminated dimer architecture linked through the inner carbons was obtained from the one-electron oxidation of CuNCC4.
29749234	1	72	theme	organocopper	141:152	arg1	CuNCC4					178:183	CuNCC4	178:183	CuNCC4	178:183	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	72	theme	organocopper	141:152	arg1	CuBN					190:193	CuBN	190:193	CuBN	190:193	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	72	theme	organocopper	141:152	arg1	CuNCC2					170:175	CuNCC2	170:175	CuNCC2	170:175	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	1	72	theme	organocopper	141:152	arg1	complexes					159:167	Stable square planar organocopper(III) complexes	120:167	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores	120:288	Stable square planar organocopper(III) complexes (CuNCC2, CuNCC4, and CuBN) supported by carbacorrole-based tetradentate macrocyclic ligands with NNNC coordination cores were synthesized, and their structures were elucidated by spectroscopic means including X-ray crystallographic analysis.
29749234	3	73	theme	corrole	932:938	arg1	complexes					951:959	regular corrole copper(II) complexes	924:959	regular corrole copper(II) complexes with an NNNN core	924:977	The remarkable stability of the high-valent Cu(III) states of the complexes stems from the closed-shell electronic structure derived from the peculiar NNNC coordination of the corrole-modified frameworks, which contrasts with the redox-noninnocent radical nature of regular corrole copper(II) complexes with an NNNN core.
29708722	0	0	theme	Lorenzini	76:84	arg1	Ampullae					64:71	the Skate Sensory Organ Ampullae	40:71	the Skate Sensory Organ Ampullae of Lorenzini	40:84	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
29708722	3	1	theme	jelly	425:429	arg1	sulfate					377:383	keratan sulfate	369:383	keratan sulfate (KS)	369:388	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	3	1	theme	jelly	425:429	arg1	component					410:418	a component	408:418	a component of a jelly that fills this sensory organ	408:459	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	1	2	theme	Lorenzini	222:230	arg1	ampullae					210:217	the ampullae	206:217	the ampullae of Lorenzini (AoL)	206:236	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	2	3	theme	changes	306:312	arg1	detection					273:281	the detection	269:281	the detection of weak electric field changes caused by the muscle contractions of their prey	269:360	This organ is responsible for the detection of weak electric field changes caused by the muscle contractions of their prey.
29708722	7	4	theme	electrical	1228:1237	arg1	signal					1239:1244	the electrical signal	1224:1244	the electrical signal	1224:1244	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	5	5	theme	monosulfated	843:854	arg1	1→					909:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	5	theme	monosulfated	843:854	arg1	unit					879:882	a monosulfated disaccharide repeating unit	841:882	a monosulfated disaccharide repeating unit	841:882	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	7	6	theme	parvalbumin	1108:1118	arg1	protein					1127:1133	parvalbumin α-like protein	1108:1133	parvalbumin α-like protein	1108:1133	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	5	7	theme	disaccharide	856:867	arg1	1→					909:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	7	theme	disaccharide	856:867	arg1	unit					879:882	a monosulfated disaccharide repeating unit	841:882	a monosulfated disaccharide repeating unit	841:882	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	4	8	from	jelly	680:684	arg1	KS					666:667	the KS	662:667	the KS from skate jelly	662:684	Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs.
29708722	4	8	from	jelly	680:684	arg1	pure					705:708	pure	705:708	pure	705:708	Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs.
29708722	4	9	theme	skate	674:678	arg1	jelly					680:684	skate jelly	674:684	skate jelly	674:684	Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs.
29708722	7	10	theme	α-like	1120:1125	arg1	protein					1127:1133	parvalbumin α-like protein	1108:1133	parvalbumin α-like protein	1108:1133	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	7	11	theme	molecular	1304:1312	arg1	basis					1314:1318	the molecular basis	1300:1318	the molecular basis for electroreception	1300:1339	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	3	12	theme	sensory	447:453	arg1	organ					455:459	this sensory organ	442:459	this sensory organ	442:459	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	6	13	theme	AoL	935:937	arg1	analysis					923:930	Proteomic analysis	913:930	Proteomic analysis of AoL	913:937	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	6	14	theme	core	1003:1006	arg1	transferrin					959:969	transferrin	959:969	transferrin	959:969	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	6	14	theme	core	1003:1006	arg1	keratin					972:978	keratin	972:978	keratin	972:978	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	6	14	theme	core	1003:1006	arg1	proteins					1008:1015	KS core proteins	1000:1015	KS core proteins	1000:1015	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	6	14	theme	core	1003:1006	arg1	mucin					985:989	mucin	985:989	mucin	985:989	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	7	15	theme	potassium	1173:1181	arg1	channels					1183:1190	calcium and potassium channels	1161:1190	channels	1183:1190	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	0	16	theme	Structural	0:9	arg1	Components					26:35	Structural and Functional Components	0:35	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.	0:85	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
29708722	5	17	contain	had	745:747	arg1	KS					742:743	This KS	737:743	This KS	737:743	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	17	contain	had	745:747	arg2	weight					761:766	a molecular weight	749:766	a molecular weight	749:766	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	6	18	theme	KS	1000:1001	arg1	transferrin					959:969	transferrin	959:969	transferrin	959:969	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	6	18	theme	KS	1000:1001	arg1	keratin					972:978	keratin	972:978	keratin	972:978	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	6	18	theme	KS	1000:1001	arg1	proteins					1008:1015	KS core proteins	1000:1015	KS core proteins	1000:1015	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	6	18	theme	KS	1000:1001	arg1	mucin					985:989	mucin	985:989	mucin	985:989	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	2	19	theme	muscle	328:333	arg1	contractions					335:346	the muscle contractions	324:346	the muscle contractions of their prey	324:360	This organ is responsible for the detection of weak electric field changes caused by the muscle contractions of their prey.
29708722	5	20	theme	GlcNAc6S	899:906	arg1	1→					909:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	20	theme	GlcNAc6S	899:906	arg1	unit					879:882	a monosulfated disaccharide repeating unit	841:882	a monosulfated disaccharide repeating unit	841:882	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	21	dep	30	777:778	arg1	to					774:775	to	774:775	to	774:775	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	1	22	theme	electrosensitive	166:181	arg1	organ					191:195	a unique electrosensitive sensory organ	157:195	a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL)	157:236	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	0	23	theme	Functional	15:24	arg1	Components					26:35	Structural and Functional Components	0:35	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.	0:85	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
29708722	5	24	theme	repeating	869:877	arg1	1→					909:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	24	theme	repeating	869:877	arg1	unit					879:882	a monosulfated disaccharide repeating unit	841:882	a monosulfated disaccharide repeating unit	841:882	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	4	25	theme	glycosaminoglycan	611:627	arg1	analysis					635:642	total glycosaminoglycan (GAG) analysis	605:642	total glycosaminoglycan (GAG) analysis	605:642	Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs.
29708722	1	26	theme	sensory	183:189	arg1	organ					191:195	a unique electrosensitive sensory organ	157:195	a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL)	157:236	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	2	27	theme	electric	291:298	arg1	changes					306:312	weak electric field changes	286:312	weak electric field changes caused by the muscle contractions of their prey	286:360	This organ is responsible for the detection of weak electric field changes caused by the muscle contractions of their prey.
29708722	1	28	theme	unique	159:164	arg1	organ					191:195	a unique electrosensitive sensory organ	157:195	a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL)	157:236	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	3	29	theme	keratan	369:375	arg1	KS					386:387	KS	386:387	KS	386:387	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	3	29	theme	keratan	369:375	arg1	sulfate					377:383	keratan sulfate	369:383	keratan sulfate (KS)	369:388	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	3	29	theme	keratan	369:375	arg1	component					410:418	a component	408:418	a component of a jelly that fills this sensory organ	408:459	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	1	30	contain	possesses	147:155	arg1	fish					114:117	a cartilaginous fish	98:117	a cartilaginous fish related to sharks and rays	98:144	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	1	30	contain	possesses	147:155	arg2	organ					191:195	a unique electrosensitive sensory organ	157:195	a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL)	157:236	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	1	30	contain	possesses	147:155	arg1	skate					91:95	The skate	87:95	The skate	87:95	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	4	31	theme	other	725:729	arg1	GAGs					731:734	no other GAGs	722:734	no other GAGs	722:734	Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs.
29708722	7	32	theme	signal	1239:1244	arg1	transduction					1208:1219	the transduction	1204:1219	the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception	1204:1339	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	2	33	theme	prey	357:360	arg1	contractions					335:346	the muscle contractions	324:346	the muscle contractions of their prey	324:360	This organ is responsible for the detection of weak electric field changes caused by the muscle contractions of their prey.
29708722	0	34	theme	Sensory	50:56	arg1	Ampullae					64:71	the Skate Sensory Organ Ampullae	40:71	the Skate Sensory Organ Ampullae of Lorenzini	40:84	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
29708722	5	35	link	N-linked	809:816	arg1	KS					818:819	N-linked KS	809:819	N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→	809:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	3	36	theme	high	492:495	arg1	conductivity					504:515	its high proton conductivity	488:515	its high proton conductivity	488:515	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	2	37	theme	field	300:304	arg1	changes					306:312	weak electric field changes	286:312	weak electric field changes caused by the muscle contractions of their prey	286:360	This organ is responsible for the detection of weak electric field changes caused by the muscle contractions of their prey.
29708722	0	38	theme	Skate	44:48	arg1	Ampullae					64:71	the Skate Sensory Organ Ampullae	40:71	the Skate Sensory Organ Ampullae of Lorenzini	40:84	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
29708722	7	39	theme	jelly	1097:1101	arg1	macrostructure					1075:1088	the macrostructure	1071:1088	the macrostructure of the jelly	1071:1101	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	3	40	theme	proton	497:502	arg1	conductivity					504:515	its high proton conductivity	488:515	its high proton conductivity	488:515	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	1	41	theme	cartilaginous	100:112	arg1	fish					114:117	a cartilaginous fish	98:117	a cartilaginous fish related to sharks and rays	98:144	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	1	41	theme	cartilaginous	100:112	arg1	skate					91:95	The skate	87:95	The skate	87:95	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	5	42	theme	Gal	889:891	arg1	1→					909:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	42	theme	Gal	889:891	arg1	unit					879:882	a monosulfated disaccharide repeating unit	841:882	a monosulfated disaccharide repeating unit	841:882	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	43	theme	1→4	894:896	arg1	1→					909:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	→3) Gal (1→4) GlcNAc6S (1→	885:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	5	43	theme	1→4	894:896	arg1	unit					879:882	a monosulfated disaccharide repeating unit	841:882	a monosulfated disaccharide repeating unit	841:882	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	2	44	theme	weak	286:289	arg1	changes					306:312	weak electric field changes	286:312	weak electric field changes caused by the muscle contractions of their prey	286:360	This organ is responsible for the detection of weak electric field changes caused by the muscle contractions of their prey.
29708722	1	45	theme	related	119:125	arg1	fish					114:117	a cartilaginous fish	98:117	a cartilaginous fish related to sharks and rays	98:144	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	1	45	theme	related	119:125	arg1	skate					91:95	The skate	87:95	The skate	87:95	The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL).
29708722	5	46	theme	N-linked	809:816	arg1	KS					818:819	N-linked KS	809:819	N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→	809:910	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	0	47	theme	Ampullae	64:71	arg1	Components					26:35	Structural and Functional Components	0:35	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.	0:85	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
29708722	5	48	theme	molecular	751:759	arg1	weight					761:766	a molecular weight	749:766	a molecular weight	749:766	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
29708722	3	49	theme	modern	518:523	arg1	methods					536:542	modern analytical methods	518:542	modern analytical methods	518:542	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	6	50	theme	Proteomic	913:921	arg1	analysis					923:930	Proteomic analysis	913:930	Proteomic analysis of AoL	913:937	Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins.
29708722	4	51	theme	total	605:609	arg1	glycosaminoglycan					611:627	total glycosaminoglycan	605:627	total glycosaminoglycan (GAG) analysis	605:642	Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs.
29708722	4	51	theme	total	605:609	arg1	GAG					630:632	GAG	630:632	GAG	630:632	Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs.
29708722	7	52	theme	calcium	1161:1167	arg1	channels					1183:1190	calcium and potassium channels	1161:1190	channels	1183:1190	Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
29708722	0	53	theme	Organ	58:62	arg1	Ampullae					64:71	the Skate Sensory Organ Ampullae	40:71	the Skate Sensory Organ Ampullae of Lorenzini	40:84	Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
29708722	3	54	theme	analytical	525:534	arg1	methods					536:542	modern analytical methods	518:542	modern analytical methods	518:542	While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization.
29708722	5	55	theme	kDa	780:782	arg1	weight					761:766	a molecular weight	749:766	a molecular weight	749:766	This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→.
31270739	0	0	theme	mass	92:95	arg1	approaches					110:119	high-throughput mass spectrometry approaches	76:119	high-throughput mass spectrometry approaches	76:119	Expanding our understanding of the role of microbial glycoproteomes through high-throughput mass spectrometry approaches.
31270739	7	1	theme	species	1200:1206	arg1	number					1180:1185	a number	1178:1185	a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia	1178:1343	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	10	2	theme	glycosylation	2026:2038	arg1	events					2040:2045	microbial glycosylation events	2016:2045	microbial glycosylation events	2016:2045	This work demonstrates that MS approaches can now be considered an indispensable tool for the elucidation and tracking of microbial glycosylation events.
31270739	1	3	theme	essential	177:185	arg1	glycosylation					130:142	Protein glycosylation	122:142	Protein glycosylation	122:142	Protein glycosylation is increasingly recognised as an essential requirement for effective microbial infections.
31270739	1	3	theme	essential	177:185	arg1	requirement					187:197	an essential requirement	174:197	an essential requirement for effective microbial infections	174:232	Protein glycosylation is increasingly recognised as an essential requirement for effective microbial infections.
31270739	6	4	theme	microbial	1071:1079	arg1	species					1081:1087	microbial species	1071:1087	microbial species	1071:1087	By developing workflows for glycopeptide enrichment and identification we have demostrated that it is now possible to characterise the glycoproteomes of microbial species in a truely high-throughput manner.
31270739	0	5	theme	high-throughput	76:90	arg1	approaches					110:119	high-throughput mass spectrometry approaches	76:119	high-throughput mass spectrometry approaches	76:119	Expanding our understanding of the role of microbial glycoproteomes through high-throughput mass spectrometry approaches.
31270739	2	6	theme	immune	394:399	arg1	response					401:408	the host immune response	385:408	the host immune response	385:408	Within microbial pathogen's protein glycosylation is used for both defensive and offensive purposes; enabling pathogens to fortify themselves against the host immune response or to disarm the host's ability to resist infection.
31270739	9	7	theme	glycosylation	1662:1674	arg1	systems					1676:1682	N-linked bacterial glycosylation systems	1643:1682	N-linked bacterial glycosylation systems	1643:1682	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	3	8	theme	glycosylation	601:613	arg1	true					578:581	true	578:581	true	578:581	Although microbial protein glycosylation systems have been recognised for nearly two decades only recently has the true extend of protein glycosylation within microbes begun to be appreciated.
31270739	0	9	theme	spectrometry	97:108	arg1	approaches					110:119	high-throughput mass spectrometry approaches	76:119	high-throughput mass spectrometry approaches	76:119	Expanding our understanding of the role of microbial glycoproteomes through high-throughput mass spectrometry approaches.
31270739	7	10	theme	bacterial	1190:1198	arg1	species					1200:1206	bacterial species	1190:1206	bacterial species	1190:1206	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	4	11	theme	modern	740:745	arg1	approaches					747:756	modern approaches	740:756	modern approaches for the characterisation of glycosylation	740:798	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	6	12	theme	glycopeptide	946:957	arg1	enrichment					959:968	glycopeptide enrichment	946:968	glycopeptide enrichment	946:968	By developing workflows for glycopeptide enrichment and identification we have demostrated that it is now possible to characterise the glycoproteomes of microbial species in a truely high-throughput manner.
31270739	2	13	theme	offensive	316:324	arg1	purposes					326:333	both defensive and offensive purposes	297:333	both defensive and offensive purposes	297:333	Within microbial pathogen's protein glycosylation is used for both defensive and offensive purposes; enabling pathogens to fortify themselves against the host immune response or to disarm the host's ability to resist infection.
31270739	10	14	dep	elucidation	1988:1998	arg1	the					1984:1986	the	1984:1986	the	1984:1986	This work demonstrates that MS approaches can now be considered an indispensable tool for the elucidation and tracking of microbial glycosylation events.
31270739	3	15	theme	microbial	472:480	arg1	systems					504:510	microbial protein glycosylation systems	472:510	microbial protein glycosylation systems	472:510	Although microbial protein glycosylation systems have been recognised for nearly two decades only recently has the true extend of protein glycosylation within microbes begun to be appreciated.
31270739	7	16	theme	multiple	1215:1222	arg1	pathogens					1286:1294	the pathogens	1282:1294	the pathogens A. baumannii, R. solanacearum and B. cenocepacia	1282:1343	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	16	theme	multiple	1215:1222	arg1	members					1243:1249	members	1243:1249	members of the Campylobacter genus	1243:1276	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	16	theme	multiple	1215:1222	arg1	proteins					1224:1231	multiple proteins	1215:1231	multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia	1215:1343	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	8	17	used	used	1511:1514	arg2	array					1490:1494	an extensive array	1477:1494	an extensive array of glycans	1477:1505	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	8	18	theme	common	1455:1460	arg1	place					1462:1466	common place	1455:1466	common place	1455:1466	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	1	19	theme	effective	203:211	arg1	infections					223:232	effective microbial infections	203:232	effective microbial infections	203:232	Protein glycosylation is increasingly recognised as an essential requirement for effective microbial infections.
31270739	7	20	theme	Campylobacter	1258:1270	arg1	genus					1272:1276	the Campylobacter genus	1254:1276	the Campylobacter genus	1254:1276	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	5	21	theme	my	822:823	arg1	research					825:832	my research	822:832	my research	822:832	Over the last decade my research has focused on the development of proteomic tools to probe microbial glycosylation.
31270739	9	22	theme	N-linked	1643:1650	arg1	systems					1676:1682	N-linked bacterial glycosylation systems	1643:1682	N-linked bacterial glycosylation systems	1643:1682	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	4	23	theme	glycosylation	786:798	arg1	characterisation					766:781	the characterisation	762:781	the characterisation of glycosylation	762:798	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	1	24	theme	microbial	213:221	arg1	infections					223:232	effective microbial infections	203:232	effective microbial infections	203:232	Protein glycosylation is increasingly recognised as an essential requirement for effective microbial infections.
31270739	7	25	theme	genus	1272:1276	arg1	pathogens					1286:1294	the pathogens	1282:1294	the pathogens A. baumannii, R. solanacearum and B. cenocepacia	1282:1343	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	25	theme	genus	1272:1276	arg1	A.					1296:1297	A.	1296:1297	A.	1296:1297	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	25	theme	genus	1272:1276	arg1	members					1243:1249	members	1243:1249	members of the Campylobacter genus	1243:1276	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	25	theme	genus	1272:1276	arg1	R.					1310:1311	R.	1310:1311	R.	1310:1311	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	25	theme	genus	1272:1276	arg1	B.					1330:1331	B.	1330:1331	B.	1330:1331	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	9	26	theme	parasitic	1834:1842	arg1	organisms					1855:1863	the parasitic eukaryotic organisms T. gondii and P. falciparum	1830:1891	the parasitic eukaryotic organisms T. gondii and P. falciparum	1830:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	7	27	dep	B.	1330:1331	arg1	cenocepacia					1333:1343	B. cenocepacia	1330:1343	B. cenocepacia	1330:1343	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	4	28	dep	development	709:719	arg1	the					705:707	the	705:707	the	705:707	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	8	29	theme	Eukaryotic	1548:1557	arg1	systems					1573:1579	Eukaryotic glycosylation systems	1548:1579	Eukaryotic glycosylation systems	1548:1579	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	8	30	theme	bacterial	1382:1390	arg1	glycosylation					1392:1404	bacterial glycosylation	1382:1404	bacterial glycosylation	1382:1404	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	3	31	theme	protein	593:599	arg1	glycosylation					601:613	protein glycosylation	593:613	protein glycosylation	593:613	Although microbial protein glycosylation systems have been recognised for nearly two decades only recently has the true extend of protein glycosylation within microbes begun to be appreciated.
31270739	10	32	theme	indispensable	1961:1973	arg1	tool					1975:1978	an indispensable tool	1958:1978	an indispensable tool for the elucidation and tracking of microbial glycosylation events	1958:2045	This work demonstrates that MS approaches can now be considered an indispensable tool for the elucidation and tracking of microbial glycosylation events.
31270739	5	33	theme	tools	878:882	arg1	development					853:863	the development	849:863	the development of proteomic tools to probe microbial glycosylation	849:915	Over the last decade my research has focused on the development of proteomic tools to probe microbial glycosylation.
31270739	5	34	theme	proteomic	868:876	arg1	tools					878:882	proteomic tools	868:882	proteomic tools	868:882	Over the last decade my research has focused on the development of proteomic tools to probe microbial glycosylation.
31270739	10	35	theme	microbial	2016:2024	arg1	events					2040:2045	microbial glycosylation events	2016:2045	microbial glycosylation events	2016:2045	This work demonstrates that MS approaches can now be considered an indispensable tool for the elucidation and tracking of microbial glycosylation events.
31270739	1	36	theme	Protein	122:128	arg1	glycosylation					130:142	Protein glycosylation	122:142	Protein glycosylation	122:142	Protein glycosylation is increasingly recognised as an essential requirement for effective microbial infections.
31270739	1	36	theme	Protein	122:128	arg1	requirement					187:197	an essential requirement	174:197	an essential requirement for effective microbial infections	174:232	Protein glycosylation is increasingly recognised as an essential requirement for effective microbial infections.
31270739	9	37	theme	bacterial	1652:1660	arg1	systems					1676:1682	N-linked bacterial glycosylation systems	1643:1682	N-linked bacterial glycosylation systems	1643:1682	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	0	38	theme	role	35:38	arg1	understanding					14:26	our understanding	10:26	our understanding of the role of microbial glycoproteomes	10:66	Expanding our understanding of the role of microbial glycoproteomes through high-throughput mass spectrometry approaches.
31270739	4	39	theme	approaches	747:756	arg1	enabler					662:668	A key enabler	656:668	A key enabler for this conceptual shift	656:694	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	4	39	theme	approaches	747:756	arg1	application					725:735	application	725:735	application	725:735	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	4	39	theme	approaches	747:756	arg1	development					709:719	development	709:719	development	709:719	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	7	40	dep	R.	1310:1311	arg1	solanacearum					1313:1324	R. solanacearum	1310:1324	R. solanacearum	1310:1324	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	9	41	theme	discovered	1723:1732	arg1	glycosylation					1784:1796	Arginine glycosylation	1775:1796	Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum	1775:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	9	41	theme	discovered	1723:1732	arg1	forms					1734:1738	newly discovered forms	1717:1738	newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum	1717:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	9	41	theme	discovered	1723:1732	arg1	glycosylation					1809:1821	glycosylation	1809:1821	Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum	1775:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	3	42	theme	glycosylation	490:502	arg1	systems					504:510	microbial protein glycosylation systems	472:510	microbial protein glycosylation systems	472:510	Although microbial protein glycosylation systems have been recognised for nearly two decades only recently has the true extend of protein glycosylation within microbes begun to be appreciated.
31270739	7	43	dep	shown	1172:1176	arg1	Using					1125:1129	Using	1125:1129	Using these high-throughput approaches	1125:1162	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	44	theme	high-throughput	1137:1151	arg1	approaches					1153:1162	these high-throughput approaches	1131:1162	these high-throughput approaches	1131:1162	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	8	45	theme	glycosylation	1559:1571	arg1	systems					1573:1579	Eukaryotic glycosylation systems	1548:1579	Eukaryotic glycosylation systems	1548:1579	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	4	46	theme	conceptual	679:688	arg1	shift					690:694	this conceptual shift	674:694	this conceptual shift	674:694	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	0	47	theme	microbial	43:51	arg1	glycoproteomes					53:66	microbial glycoproteomes	43:66	microbial glycoproteomes	43:66	Expanding our understanding of the role of microbial glycoproteomes through high-throughput mass spectrometry approaches.
31270739	6	48	theme	high-throughput	1101:1115	arg1	manner					1117:1122	a truely high-throughput manner	1092:1122	a truely high-throughput manner	1092:1122	By developing workflows for glycopeptide enrichment and identification we have demostrated that it is now possible to characterise the glycoproteomes of microbial species in a truely high-throughput manner.
31270739	5	49	theme	last	810:813	arg1	decade					815:820	the last decade	806:820	the last decade	806:820	Over the last decade my research has focused on the development of proteomic tools to probe microbial glycosylation.
31270739	2	50	theme	protein	263:269	arg1	glycosylation					271:283	microbial pathogen's protein glycosylation	242:283	microbial pathogen's protein glycosylation	242:283	Within microbial pathogen's protein glycosylation is used for both defensive and offensive purposes; enabling pathogens to fortify themselves against the host immune response or to disarm the host's ability to resist infection.
31270739	2	51	theme	host	389:392	arg1	response					401:408	the host immune response	385:408	the host immune response	385:408	Within microbial pathogen's protein glycosylation is used for both defensive and offensive purposes; enabling pathogens to fortify themselves against the host immune response or to disarm the host's ability to resist infection.
31270739	7	52	dep	number	1180:1185	arg1	modify					1208:1213	modify	1208:1213	modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia	1208:1343	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	9	53	dep	organisms	1855:1863	arg1	gondii					1868:1873	T. gondii	1865:1873	T. gondii	1865:1873	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	9	53	dep	organisms	1855:1863	arg1	falciparum					1882:1891	P. falciparum	1879:1891	P. falciparum	1879:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	9	54	link	N-linked	1643:1650	arg1	systems					1676:1682	N-linked bacterial glycosylation systems	1643:1682	N-linked bacterial glycosylation systems	1643:1682	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	8	55	theme	glycans	1499:1505	arg1	array					1490:1494	an extensive array	1477:1494	an extensive array of glycans	1477:1505	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	3	56	dep	true	578:581	arg1	extend					583:588	extend	583:588	extend	583:588	Although microbial protein glycosylation systems have been recognised for nearly two decades only recently has the true extend of protein glycosylation within microbes begun to be appreciated.
31270739	6	57	gly	glycopeptide	946:957	arg2	glycopeptide					946:957	glycopeptide enrichment	946:968	glycopeptide enrichment	946:968	By developing workflows for glycopeptide enrichment and identification we have demostrated that it is now possible to characterise the glycoproteomes of microbial species in a truely high-throughput manner.
31270739	9	58	theme	Arginine	1775:1782	arg1	glycosylation					1784:1796	Arginine glycosylation	1775:1796	Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum	1775:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	7	59	dep	pathogens	1286:1294	arg1	pathogens					1286:1294	the pathogens	1282:1294	the pathogens A. baumannii, R. solanacearum and B. cenocepacia	1282:1343	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	59	dep	pathogens	1286:1294	arg1	A.					1296:1297	A.	1296:1297	A.	1296:1297	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	59	dep	pathogens	1286:1294	arg1	R.					1310:1311	R.	1310:1311	R.	1310:1311	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	7	59	dep	pathogens	1286:1294	arg1	B.					1330:1331	B.	1330:1331	B.	1330:1331	Using these high-throughput approaches we have shown a number of bacterial species modify multiple proteins including members of the Campylobacter genus and the pathogens A. baumannii, R. solanacearum and B. cenocepacia.
31270739	2	60	theme	microbial	242:250	arg1	glycosylation					271:283	microbial pathogen's protein glycosylation	242:283	microbial pathogen's protein glycosylation	242:283	Within microbial pathogen's protein glycosylation is used for both defensive and offensive purposes; enabling pathogens to fortify themselves against the host immune response or to disarm the host's ability to resist infection.
31270739	2	61	theme	defensive	302:310	arg1	purposes					326:333	both defensive and offensive purposes	297:333	both defensive and offensive purposes	297:333	Within microbial pathogen's protein glycosylation is used for both defensive and offensive purposes; enabling pathogens to fortify themselves against the host immune response or to disarm the host's ability to resist infection.
31270739	9	62	theme	eukaryotic	1844:1853	arg1	organisms					1855:1863	the parasitic eukaryotic organisms T. gondii and P. falciparum	1830:1891	the parasitic eukaryotic organisms T. gondii and P. falciparum	1830:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	8	63	theme	extensive	1480:1488	arg1	array					1490:1494	an extensive array	1477:1494	an extensive array of glycans	1477:1505	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	10	64	theme	events	2040:2045	arg1	tracking					2004:2011	tracking	2004:2011	tracking	2004:2011	This work demonstrates that MS approaches can now be considered an indispensable tool for the elucidation and tracking of microbial glycosylation events.
31270739	10	64	theme	events	2040:2045	arg1	elucidation					1988:1998	elucidation	1988:1998	elucidation	1988:1998	This work demonstrates that MS approaches can now be considered an indispensable tool for the elucidation and tracking of microbial glycosylation events.
31270739	8	65	theme	glycan	1426:1431	arg1	microheterogeneity					1433:1450	glycan microheterogeneity	1426:1450	glycan microheterogeneity	1426:1450	These studies have established that bacterial glycosylation is widespread, that glycan microheterogeneity is common place and that an extensive array of glycans are used to decorate protein compared to Eukaryotic glycosylation systems.
31270739	5	66	theme	microbial	893:901	arg1	glycosylation					903:915	microbial glycosylation	893:915	microbial glycosylation	893:915	Over the last decade my research has focused on the development of proteomic tools to probe microbial glycosylation.
31270739	9	67	theme	glycosylation	1753:1765	arg1	glycosylation					1784:1796	Arginine glycosylation	1775:1796	Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum	1775:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	9	67	theme	glycosylation	1753:1765	arg1	forms					1734:1738	newly discovered forms	1717:1738	newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum	1717:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	9	67	theme	glycosylation	1753:1765	arg1	glycosylation					1809:1821	glycosylation	1809:1821	Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum	1775:1891	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	3	68	theme	protein	482:488	arg1	systems					504:510	microbial protein glycosylation systems	472:510	microbial protein glycosylation systems	472:510	Although microbial protein glycosylation systems have been recognised for nearly two decades only recently has the true extend of protein glycosylation within microbes begun to be appreciated.
31270739	0	69	theme	glycoproteomes	53:66	arg1	role					35:38	the role	31:38	the role of microbial glycoproteomes	31:66	Expanding our understanding of the role of microbial glycoproteomes through high-throughput mass spectrometry approaches.
31270739	6	70	theme	species	1081:1087	arg1	glycoproteomes					1053:1066	the glycoproteomes	1049:1066	the glycoproteomes of microbial species	1049:1087	By developing workflows for glycopeptide enrichment and identification we have demostrated that it is now possible to characterise the glycoproteomes of microbial species in a truely high-throughput manner.
31270739	10	71	theme	MS	1922:1923	arg1	approaches					1925:1934	MS approaches	1922:1934	MS approaches	1922:1934	This work demonstrates that MS approaches can now be considered an indispensable tool for the elucidation and tracking of microbial glycosylation events.
31270739	9	72	theme	microbial	1743:1751	arg1	glycosylation					1753:1765	microbial glycosylation	1743:1765	microbial glycosylation	1743:1765	Excitingly these approaches developed to characterise O- and N-linked bacterial glycosylation systems are equally amenable to studying newly discovered forms of microbial glycosylation such as Arginine glycosylation as well as glycosylation within the parasitic eukaryotic organisms T. gondii and P. falciparum.
31270739	4	73	theme	key	658:660	arg1	development					709:719	development	709:719	development	709:719	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
31270739	4	73	theme	key	658:660	arg1	enabler					662:668	A key enabler	656:668	A key enabler for this conceptual shift	656:694	A key enabler for this conceptual shift has been the development and application of modern approaches for the characterisation of glycosylation.
30520972	3	0	theme	Capsule	357:363	arg1	CapsNet					374:380	CapsNet	374:380	CapsNet	374:380	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	3	0	theme	Capsule	357:363	arg1	architecture					343:354	A recent deep-learning architecture	320:354	A recent deep-learning architecture	320:354	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	3	0	theme	Capsule	357:363	arg1	Network					365:371	Capsule Network	357:371	Capsule Network (CapsNet)	357:381	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	6	1	theme	capsule	1010:1016	arg1	length					1018:1023	The capsule length	1006:1023	The capsule length	1006:1023	The capsule length also gives an accurate estimate for the confidence of the PTM prediction.
30520972	7	2	theme	sites	1214:1218	arg1	detector					1186:1193	a motif detector	1178:1193	a motif detector of phosphorylation sites	1178:1218	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	7	2	theme	sites	1214:1218	arg1	features					1149:1156	the internal capsule features	1128:1156	the internal capsule features	1128:1156	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	3	3	theme	small	532:536	arg1	data					547:550	small training data	532:550	small training data	532:550	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	7	4	theme	internal	1132:1139	arg1	detector					1186:1193	a motif detector	1178:1193	a motif detector of phosphorylation sites	1178:1218	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	7	4	theme	internal	1132:1139	arg1	features					1149:1156	the internal capsule features	1128:1156	the internal capsule features	1128:1156	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	6	5	theme	prediction	1087:1096	arg1	confidence					1065:1074	the confidence	1061:1074	the confidence of the PTM prediction	1061:1096	The capsule length also gives an accurate estimate for the confidence of the PTM prediction.
30520972	5	6	theme	other	870:874	arg1	tools					887:891	other well-known tools	870:891	other well-known tools in most cases	870:905	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	5	7	theme	well-known	876:885	arg1	tools					887:891	other well-known tools	870:891	other well-known tools in most cases	870:905	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	5	8	theme	training	991:998	arg1	data					1000:1003	small training data	985:1003	small training data	985:1003	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	1	9	theme	useful	186:191	arg1	approach					193:200	a useful approach	184:200	a useful approach for studying protein functions	184:231	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	2	10	contain	has	282:284	arg2	room					298:301	significant room	286:301	significant room for improvement	286:317	The prediction accuracy of the existing methods has significant room for improvement.
30520972	2	10	contain	has	282:284	arg1	accuracy					249:256	The prediction accuracy	234:256	The prediction accuracy of the existing methods	234:280	The prediction accuracy of the existing methods has significant room for improvement.
30520972	5	11	theme	baseline	804:811	arg1	architecture					842:853	the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases	800:905	architecture	842:853	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	4	12	dep	RESULTS	553:559	arg1	proposed					564:571	proposed	564:571	proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites	564:772	RESULTS We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites.
30520972	9	13	from	mechanism	1486:1494	arg1	problems					1555:1562	other bioinformatic problems	1535:1562	other bioinformatic problems	1535:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	11	14	theme	Supplementary	1702:1714	arg1	data					1716:1719	SUPPLEMENTARY INFORMATION Supplementary data	1676:1719	SUPPLEMENTARY INFORMATION Supplementary data	1676:1719	SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
30520972	10	15	dep	AVAILABILITY	1565:1576	arg1	free					1611:1614	free	1611:1614	free	1611:1614	AVAILABILITY AND IMPLEMENTATION The codes are free to download from https://github.com/duolinwang/CapsNet_PTM.
30520972	5	16	from	tools	887:891	arg1	cases					901:905	most cases	896:905	most cases	896:905	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	5	17	theme	convolutional	813:825	arg1	architecture					842:853	the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases	800:905	architecture	842:853	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	10	18	from	https	1633:1637	arg1	download					1619:1626	download	1619:1626	download from https	1619:1637	AVAILABILITY AND IMPLEMENTATION The codes are free to download from https://github.com/duolinwang/CapsNet_PTM.
30520972	7	19	theme	phosphorylation	1198:1212	arg1	sites					1214:1218	phosphorylation sites	1198:1218	phosphorylation sites	1198:1218	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	7	20	theme	phosphorylation	1244:1258	arg1	labels					1260:1265	no kinase-specific phosphorylation labels	1225:1265	no kinase-specific phosphorylation labels	1225:1265	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	1	21	theme	MOTIVATION	77:86	arg1	methods					102:108	MOTIVATION Computational methods	77:108	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction	77:174	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	5	22	theme	neural	827:832	arg1	architecture					842:853	the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases	800:905	architecture	842:853	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	7	23	theme	motif	1180:1184	arg1	detector					1186:1193	a motif detector	1178:1193	a motif detector of phosphorylation sites	1178:1218	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	7	23	theme	motif	1180:1184	arg1	features					1149:1156	the internal capsule features	1128:1156	the internal capsule features	1128:1156	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	11	24	theme	INFORMATION	1690:1700	arg1	data					1716:1719	SUPPLEMENTARY INFORMATION Supplementary data	1676:1719	SUPPLEMENTARY INFORMATION Supplementary data	1676:1719	SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
30520972	1	25	theme	Computational	88:100	arg1	methods					102:108	MOTIVATION Computational methods	77:108	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction	77:174	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	8	26	theme	discriminant	1353:1364	arg1	power					1366:1370	strong discriminant power	1346:1370	strong discriminant power	1346:1370	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	5	27	theme	network	834:840	arg1	architecture					842:853	the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases	800:905	architecture	842:853	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	9	28	theme	bioinformatic	1541:1553	arg1	problems					1555:1562	other bioinformatic problems	1535:1562	other bioinformatic problems	1535:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	0	29	theme	modification	47:58	arg1	prediction					65:74	protein post-translational modification site prediction	20:74	protein post-translational modification site prediction	20:74	Capsule network for protein post-translational modification site prediction.
30520972	3	30	theme	great	474:478	arg1	opportunity					480:490	a great opportunity	472:490	a great opportunity to solve this problem	472:512	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	3	31	theme	internal	411:418	arg1	representation					433:446	the internal hierarchical representation	407:446	the internal hierarchical representation of input data	407:460	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	9	32	theme	recognition	1474:1484	arg1	mechanism					1486:1494	the recognition mechanism	1470:1494	the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems	1470:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	9	33	from	PTMs	1499:1502	arg1	problems					1555:1562	other bioinformatic problems	1535:1562	other bioinformatic problems	1535:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	3	34	theme	hierarchical	420:431	arg1	representation					433:446	the internal hierarchical representation	407:446	the internal hierarchical representation of input data	407:460	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	1	35	theme	protein	114:120	arg1	modification					141:152	protein post-translational modification	114:152	protein post-translational modification (PTM) site prediction	114:174	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	1	36	theme	protein	215:221	arg1	functions					223:231	protein functions	215:231	protein functions	215:231	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	0	37	theme	protein	20:26	arg1	prediction					65:74	protein post-translational modification site prediction	20:74	protein post-translational modification site prediction	20:74	Capsule network for protein post-translational modification site prediction.
30520972	9	38	from	problems	1555:1562	arg1	mechanism					1486:1494	the recognition mechanism	1470:1494	the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems	1470:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	11	39	theme	Bioinformatics	1738:1751	arg1	online					1753:1758	Bioinformatics online	1738:1758	Bioinformatics online	1738:1758	SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
30520972	1	40	theme	post-translational	122:139	arg1	modification					141:152	protein post-translational modification	114:152	protein post-translational modification (PTM) site prediction	114:174	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	8	41	theme	kinase	1390:1395	arg1	substrates					1397:1406	kinase substrates	1390:1406	kinase substrates	1390:1406	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	5	42	theme	promising	920:928	arg1	results					930:936	promising results	920:936	promising results	920:936	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	4	43	theme	protein	598:604	arg1	sites					610:614	protein PTM sites	598:614	protein PTM sites	598:614	RESULTS We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites.
30520972	1	44	theme	modification	141:152	arg1	PTM					155:157	PTM	155:157	PTM	155:157	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	1	44	theme	modification	141:152	arg1	prediction					165:174	protein post-translational modification (PTM) site prediction	114:174	protein post-translational modification (PTM) site prediction	114:174	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	4	45	theme	PTM	606:608	arg1	sites					610:614	protein PTM sites	598:614	protein PTM sites	598:614	RESULTS We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites.
30520972	3	46	theme	input	451:455	arg1	data					457:460	input data	451:460	input data	451:460	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	8	47	theme	different	1413:1421	arg1	families					1430:1437	different kinase families	1413:1437	different kinase families	1413:1437	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	5	48	dep	architecture	842:853	arg1	MusiteDeep					855:864	MusiteDeep	855:864	MusiteDeep	855:864	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	4	49	link	N-linked	644:651	arg1	glycosylation					653:665	N-linked glycosylation	644:665	N-linked glycosylation	644:665	RESULTS We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites.
30520972	2	50	theme	existing	265:272	arg1	methods					274:280	the existing methods	261:280	the existing methods	261:280	The prediction accuracy of the existing methods has significant room for improvement.
30520972	5	51	theme	practical	942:950	arg1	use					952:954	practical use	942:954	practical use	942:954	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	0	52	theme	post-translational	28:45	arg1	prediction					65:74	protein post-translational modification site prediction	20:74	protein post-translational modification site prediction	20:74	Capsule network for protein post-translational modification site prediction.
30520972	3	53	theme	data	457:460	arg1	representation					433:446	the internal hierarchical representation	407:446	the internal hierarchical representation of input data	407:460	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	6	54	theme	PTM	1083:1085	arg1	prediction					1087:1096	the PTM prediction	1079:1096	the PTM prediction	1079:1096	The capsule length also gives an accurate estimate for the confidence of the PTM prediction.
30520972	8	55	contain	have	1341:1344	arg1	representations					1320:1334	robust representations	1313:1334	robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families	1313:1437	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	8	55	contain	have	1341:1344	arg2	power					1366:1370	strong discriminant power	1346:1370	strong discriminant power	1346:1370	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	9	56	theme	other	1535:1539	arg1	problems					1555:1562	other bioinformatic problems	1535:1562	other bioinformatic problems	1535:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	10	57	dep	The	1597:1599	arg1	codes					1601:1605	codes	1601:1605	codes	1601:1605	AVAILABILITY AND IMPLEMENTATION The codes are free to download from https://github.com/duolinwang/CapsNet_PTM.
30520972	5	58	theme	most	896:899	arg1	cases					901:905	most cases	896:905	most cases	896:905	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	9	59	from	applications	1508:1519	arg1	problems					1555:1562	other bioinformatic problems	1535:1562	other bioinformatic problems	1535:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	8	60	theme	kinase	1423:1428	arg1	families					1430:1437	different kinase families	1413:1437	different kinase families	1413:1437	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	0	61	theme	site	60:63	arg1	prediction					65:74	protein post-translational modification site prediction	20:74	protein post-translational modification site prediction	20:74	Capsule network for protein post-translational modification site prediction.
30520972	9	62	theme	PTMs	1499:1502	arg1	mechanism					1486:1494	the recognition mechanism	1470:1494	the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems	1470:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	7	63	theme	capsule	1141:1147	arg1	detector					1186:1193	a motif detector	1178:1193	a motif detector of phosphorylation sites	1178:1218	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	7	63	theme	capsule	1141:1147	arg1	features					1149:1156	the internal capsule features	1128:1156	the internal capsule features	1128:1156	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	2	64	theme	prediction	238:247	arg1	accuracy					249:256	The prediction accuracy	234:256	The prediction accuracy of the existing methods	234:280	The prediction accuracy of the existing methods has significant room for improvement.
30520972	3	65	theme	training	538:545	arg1	data					547:550	small training data	532:550	small training data	532:550	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	6	66	dep	accurate	1039:1046	arg1	estimate					1048:1055	estimate	1048:1055	estimate	1048:1055	The capsule length also gives an accurate estimate for the confidence of the PTM prediction.
30520972	3	67	theme	recent	322:327	arg1	architecture					343:354	A recent deep-learning architecture	320:354	A recent deep-learning architecture	320:354	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	3	67	theme	recent	322:327	arg1	Network					365:371	Capsule Network	357:371	Capsule Network (CapsNet)	357:381	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	7	68	theme	kinase-specific	1228:1242	arg1	labels					1260:1265	no kinase-specific phosphorylation labels	1225:1265	no kinase-specific phosphorylation labels	1225:1265	We further demonstrated that the internal capsule features could be trained as a motif detector of phosphorylation sites when no kinase-specific phosphorylation labels were provided.
30520972	11	69	from	online	1753:1758	arg1	available					1725:1733	available	1725:1733	available	1725:1733	SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
30520972	9	70	theme	applications	1508:1519	arg1	mechanism					1486:1494	the recognition mechanism	1470:1494	the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems	1470:1562	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	3	71	theme	deep-learning	329:341	arg1	architecture					343:354	A recent deep-learning architecture	320:354	A recent deep-learning architecture	320:354	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	3	71	theme	deep-learning	329:341	arg1	Network					365:371	Capsule Network	357:371	Capsule Network (CapsNet)	357:381	A recent deep-learning architecture, Capsule Network (CapsNet), which can characterize the internal hierarchical representation of input data, presents a great opportunity to solve this problem, especially using small training data.
30520972	5	72	from	architecture	842:853	arg1	cases					901:905	most cases	896:905	most cases	896:905	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	2	73	theme	significant	286:296	arg1	room					298:301	significant room	286:301	significant room for improvement	286:317	The prediction accuracy of the existing methods has significant room for improvement.
30520972	1	74	theme	site	160:163	arg1	PTM					155:157	PTM	155:157	PTM	155:157	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	1	74	theme	site	160:163	arg1	prediction					165:174	protein post-translational modification (PTM) site prediction	114:174	protein post-translational modification (PTM) site prediction	114:174	MOTIVATION Computational methods for protein post-translational modification (PTM) site prediction provide a useful approach for studying protein functions.
30520972	8	75	theme	robust	1313:1318	arg1	representations					1320:1334	robust representations	1313:1334	robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families	1313:1437	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	4	76	theme	SUMOylation	756:766	arg1	sites					768:772	SUMOylation sites	756:772	SUMOylation sites	756:772	RESULTS We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites.
30520972	8	77	theme	strong	1346:1351	arg1	power					1366:1370	strong discriminant power	1346:1370	strong discriminant power	1346:1370	In addition, CapsNet generates robust representations that have strong discriminant power in distinguishing kinase substrates from different kinase families.
30520972	9	78	theme	CapsNet	1524:1530	arg1	applications					1508:1519	applications	1508:1519	applications	1508:1519	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	9	78	theme	CapsNet	1524:1530	arg1	PTMs					1499:1502	PTMs	1499:1502	PTMs	1499:1502	Our study sheds some light on the recognition mechanism of PTMs and applications of CapsNet on other bioinformatic problems.
30520972	10	79	dep	//github.com/duolinwang/CapsNet_PTM	1639:1673	arg1	IMPLEMENTATION					1582:1595	IMPLEMENTATION	1582:1595	IMPLEMENTATION	1582:1595	AVAILABILITY AND IMPLEMENTATION The codes are free to download from https://github.com/duolinwang/CapsNet_PTM.
30520972	10	79	dep	//github.com/duolinwang/CapsNet_PTM	1639:1673	arg1	AVAILABILITY					1565:1576	AVAILABILITY	1565:1576	AVAILABILITY	1565:1576	AVAILABILITY AND IMPLEMENTATION The codes are free to download from https://github.com/duolinwang/CapsNet_PTM.
30520972	2	80	theme	methods	274:280	arg1	accuracy					249:256	The prediction accuracy	234:256	The prediction accuracy of the existing methods	234:280	The prediction accuracy of the existing methods has significant room for improvement.
30520972	5	81	theme	small	985:989	arg1	data					1000:1003	small training data	985:1003	small training data	985:1003	The CapsNet outperformed the baseline convolutional neural network architecture MusiteDeep and other well-known tools in most cases and provided promising results for practical use, especially in learning from small training data.
30520972	11	82	theme	SUPPLEMENTARY	1676:1688	arg1	data					1716:1719	SUPPLEMENTARY INFORMATION Supplementary data	1676:1719	SUPPLEMENTARY INFORMATION Supplementary data	1676:1719	SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
30520972	4	83	theme	N-linked	644:651	arg1	glycosylation					653:665	N-linked glycosylation	644:665	N-linked glycosylation	644:665	RESULTS We proposed a CapsNet for predicting protein PTM sites, including phosphorylation, N-linked glycosylation, N6-acetyllysine, methyl-arginine, S-palmitoyl-cysteine, pyrrolidone-carboxylic-acid and SUMOylation sites.
29745666	0	0	theme	Sodium	93:98	arg1	Detergent					113:121	Sodium Deoxycholate Detergent	93:121	Sodium Deoxycholate Detergent	93:121	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	4	1	gly	glycoproteins	664:676	arg1	glycoproteins					664:676	glycoproteins	664:676	glycoproteins derived from biological samples such as cancer cell lines	664:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	3	2	theme	preparation	524:534	arg1	protocols					536:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols are needed.
29745666	1	3	theme	multiple	261:268	arg1	diseases					270:277	multiple diseases	261:277	multiple diseases	261:277	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	7	4	theme	lysis	1116:1120	arg1	buffer					1122:1127	SDC lysis buffer	1112:1127	SDC lysis buffer	1112:1127	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	1	5	from	modification	185:196	arg1	organisms					214:222	living organisms	207:222	living organisms	207:222	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	4	6	theme	sodium	590:595	arg1	deoxycholate					597:608	sodium deoxycholate	590:608	sodium deoxycholate	590:608	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	8	7	theme	overall	1200:1206	arg1	increase					1208:1215	a significant overall increase	1186:1215	a significant overall increase in the intensities of N-glycans released from cancer cell lines	1186:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	7	8	theme	cell	1147:1150	arg1	disruption					1152:1161	cell disruption	1147:1161	cell disruption	1147:1161	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	8	9	theme	cancer	1263:1268	arg1	lines					1275:1279	cancer cell lines	1263:1279	cancer cell lines	1263:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	0	10	theme	Deoxycholate	100:111	arg1	Detergent					113:121	Sodium Deoxycholate Detergent	93:121	Sodium Deoxycholate Detergent	93:121	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	1	11	from	biomarker	310:318	arg1	organisms					214:222	living organisms	207:222	living organisms	207:222	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	4	12	theme	cancer	718:723	arg1	lines					730:734	cancer cell lines	718:734	cancer cell lines	718:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	6	13	theme	phase	999:1003	arg1	transfer					1005:1012	ethyl acetate phase transfer	985:1012	acidic precipitation rather than ethyl acetate phase transfer	952:1012	SDC removal was determined to be more efficient when using acidic precipitation rather than ethyl acetate phase transfer.
29745666	5	14	theme	filter-aided	753:764	arg1	preparation					773:783	the filter-aided sample preparation	749:783	the filter-aided sample preparation approach	749:792	Compared to the filter-aided sample preparation approach, the sodium deoxycholate (SDC) assisted approach was determined to be more efficient and unbiased.
29745666	3	15	theme	unbiased	508:515	arg1	protocols					536:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols are needed.
29745666	5	16	theme	sample	766:771	arg1	preparation					773:783	the filter-aided sample preparation	749:783	the filter-aided sample preparation approach	749:792	Compared to the filter-aided sample preparation approach, the sodium deoxycholate (SDC) assisted approach was determined to be more efficient and unbiased.
29745666	2	17	theme	LC-MS	466:470	arg1	analysis					472:479	LC-MS analysis	466:479	LC-MS analysis	466:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	4	18	theme	glycoproteins	664:676	arg1	N-glycans					651:659	N-glycans	651:659	N-glycans of glycoproteins derived from biological samples such as cancer cell lines	651:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	0	19	theme	Quantitative	9:20	arg1	Analysis					31:38	Enhanced Quantitative LC-MS/MS Analysis	0:38	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans	0:58	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	6	20	theme	SDC	893:895	arg1	removal					897:903	SDC removal	893:903	SDC removal	893:903	SDC removal was determined to be more efficient when using acidic precipitation rather than ethyl acetate phase transfer.
29745666	4	21	theme	biological	691:700	arg1	lines					730:734	cancer cell lines	718:734	cancer cell lines	718:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	4	21	theme	biological	691:700	arg1	samples					702:708	biological samples	691:708	biological samples such as cancer cell lines	691:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	0	22	theme	Enhanced	0:7	arg1	Analysis					31:38	Enhanced Quantitative LC-MS/MS Analysis	0:38	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans	0:58	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	6	23	theme	acetate	991:997	arg1	transfer					1005:1012	ethyl acetate phase transfer	985:1012	acidic precipitation rather than ethyl acetate phase transfer	952:1012	SDC removal was determined to be more efficient when using acidic precipitation rather than ethyl acetate phase transfer.
29745666	0	24	link	N-linked	43:50	arg1	Glycans					52:58	N-linked Glycans	43:58	N-linked Glycans	43:58	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	9	25	theme	approach	1311:1318	arg1	use					1300:1302	the use	1296:1302	the use of SDC approach	1296:1318	Additionally, the use of SDC approach was also shown to be more reproducible than those methods that do not use SDC.
29745666	9	25	theme	approach	1311:1318	arg1	reproducible					1346:1357	reproducible	1346:1357	reproducible	1346:1357	Additionally, the use of SDC approach was also shown to be more reproducible than those methods that do not use SDC.
29745666	1	26	theme	living	207:212	arg1	organisms					214:222	living organisms	207:222	living organisms	207:222	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	2	27	theme	prior	457:461	arg1	glycoproteins					443:455	glycoproteins	443:455	glycoproteins prior to LC-MS analysis	443:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	5	28	theme	assisted	825:832	arg1	approach					834:841	the sodium deoxycholate (SDC) assisted approach	795:841	the sodium deoxycholate (SDC) assisted approach	795:841	Compared to the filter-aided sample preparation approach, the sodium deoxycholate (SDC) assisted approach was determined to be more efficient and unbiased.
29745666	5	28	theme	assisted	825:832	arg1	efficient					869:877	efficient	869:877	efficient	869:877	Compared to the filter-aided sample preparation approach, the sodium deoxycholate (SDC) assisted approach was determined to be more efficient and unbiased.
29745666	7	29	theme	SDC	1112:1114	arg1	buffer					1122:1127	SDC lysis buffer	1112:1127	SDC lysis buffer	1112:1127	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	3	30	theme	Convenient	482:491	arg1	protocols					536:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols are needed.
29745666	0	31	theme	LC-MS/MS	22:29	arg1	Analysis					31:38	Enhanced Quantitative LC-MS/MS Analysis	0:38	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans	0:58	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	2	32	theme	crucial	385:391	arg1	step					393:396	a crucial step	383:396	a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis	383:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	2	32	theme	crucial	385:391	arg1	extraction					369:378	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	2	33	attach	derived	430:436	arg2	N-glycans					420:428	N-glycans	420:428	N-glycans derived from glycoproteins prior to LC-MS analysis	420:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	2	33	attach	derived	430:436	arg1	glycoproteins					443:455	glycoproteins	443:455	glycoproteins prior to LC-MS analysis	443:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	1	34	theme	Protein	124:130	arg1	glycosylation					132:144	Protein glycosylation	124:144	Protein glycosylation	124:144	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	34	theme	Protein	124:130	arg1	modification					185:196	a common protein post-translational modification	149:196	a common protein post-translational modification (PTM)	149:202	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	35	mod	modification	185:196	arg1	diseases					328:335	such diseases	323:335	such diseases	323:335	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	35	mod	modification	185:196	arg3	protein					158:164	a common protein post-translational modification	149:196	a common protein post-translational modification (PTM)	149:202	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	0	36	theme	N-linked	43:50	arg1	Glycans					52:58	N-linked Glycans	43:58	N-linked Glycans	43:58	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	3	37	theme	sample	517:522	arg1	protocols					536:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols are needed.
29745666	4	38	attach	derived	678:684	arg1	lines					730:734	cancer cell lines	718:734	cancer cell lines	718:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	4	38	attach	derived	678:684	arg1	samples					702:708	biological samples	691:708	biological samples such as cancer cell lines	691:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	4	38	attach	derived	678:684	arg2	glycoproteins					664:676	glycoproteins	664:676	glycoproteins derived from biological samples such as cancer cell lines	664:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	2	39	theme	N-glycans	420:428	arg1	preparation					405:415	the preparation	401:415	the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis	401:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	4	40	theme	cell	725:728	arg1	lines					730:734	cancer cell lines	718:734	cancer cell lines	718:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	8	41	theme	N-glycans	1239:1247	arg1	intensities					1224:1234	the intensities	1220:1234	the intensities of N-glycans released from cancer cell lines	1220:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	7	42	theme	proteins/glycoproteins	1039:1060	arg1	extraction					1025:1034	Efficient extraction	1015:1034	Efficient extraction of proteins/glycoproteins from biological samples	1015:1084	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	8	43	theme	cell	1270:1273	arg1	lines					1275:1279	cancer cell lines	1263:1279	cancer cell lines	1263:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	6	44	theme	acidic	952:957	arg1	precipitation					959:971	acidic precipitation	952:971	acidic precipitation rather than ethyl acetate phase transfer	952:1012	SDC removal was determined to be more efficient when using acidic precipitation rather than ethyl acetate phase transfer.
29745666	6	45	theme	ethyl	985:989	arg1	transfer					1005:1012	ethyl acetate phase transfer	985:1012	acidic precipitation rather than ethyl acetate phase transfer	952:1012	SDC removal was determined to be more efficient when using acidic precipitation rather than ethyl acetate phase transfer.
29745666	2	46	from	step	393:396	arg1	preparation					405:415	the preparation	401:415	the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis	401:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	2	47	theme	protein/glycoprotein	348:367	arg1	step					393:396	a crucial step	383:396	a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis	383:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	2	47	theme	protein/glycoprotein	348:367	arg1	extraction					369:378	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	0	48	theme	Glycans	52:58	arg1	Analysis					31:38	Enhanced Quantitative LC-MS/MS Analysis	0:38	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans	0:58	Enhanced Quantitative LC-MS/MS Analysis of N-linked Glycans Derived from Glycoproteins Using Sodium Deoxycholate Detergent.
29745666	2	49	gly	protein/glycoprotein	348:367	arg1	protein/glycoprotein					348:367	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	8	50	from	increase	1208:1215	arg1	intensities					1224:1234	the intensities	1220:1234	the intensities of N-glycans released from cancer cell lines	1220:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	2	51	theme	Efficient	338:346	arg1	step					393:396	a crucial step	383:396	a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis	383:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	2	51	theme	Efficient	338:346	arg1	extraction					369:378	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction	338:378	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	1	52	theme	such	323:326	arg1	diseases					328:335	such diseases	323:335	such diseases	323:335	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	7	53	theme	biological	1067:1076	arg1	samples					1078:1084	biological samples	1067:1084	biological samples	1067:1084	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	8	54	theme	significant	1188:1198	arg1	increase					1208:1215	a significant overall increase	1186:1215	a significant overall increase in the intensities of N-glycans released from cancer cell lines	1186:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	8	55	attach	released	1249:1256	arg1	lines					1275:1279	cancer cell lines	1263:1279	cancer cell lines	1263:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	8	55	attach	released	1249:1256	arg2	N-glycans					1239:1247	N-glycans	1239:1247	N-glycans released from cancer cell lines	1239:1279	This was suggested by a significant overall increase in the intensities of N-glycans released from cancer cell lines.
29745666	3	56	theme	efficient	494:502	arg1	protocols					536:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols	482:544	Convenient, efficient and unbiased sample preparation protocols are needed.
29745666	4	57	theme	acidic	616:621	arg1	detergent					630:638	sodium deoxycholate (SDC) acidic labile detergent	590:638	sodium deoxycholate (SDC) acidic labile detergent	590:638	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	4	58	dep	acidic	616:621	arg1	deoxycholate					597:608	sodium deoxycholate	590:608	sodium deoxycholate	590:608	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	1	59	theme	common	151:156	arg1	PTM					199:201	PTM	199:201	PTM	199:201	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	59	theme	common	151:156	arg1	modification					185:196	a common protein post-translational modification	149:196	a common protein post-translational modification (PTM)	149:202	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	59	theme	common	151:156	arg1	glycosylation					132:144	Protein glycosylation	124:144	Protein glycosylation	124:144	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	7	60	from	samples	1078:1084	arg1	extraction					1025:1034	Efficient extraction	1015:1034	Efficient extraction of proteins/glycoproteins from biological samples	1015:1084	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	5	61	theme	preparation	773:783	arg1	approach					785:792	the filter-aided sample preparation approach	749:792	the filter-aided sample preparation approach	749:792	Compared to the filter-aided sample preparation approach, the sodium deoxycholate (SDC) assisted approach was determined to be more efficient and unbiased.
29745666	9	62	theme	SDC	1307:1309	arg1	approach					1311:1318	SDC approach	1307:1318	SDC approach	1307:1318	Additionally, the use of SDC approach was also shown to be more reproducible than those methods that do not use SDC.
29745666	2	63	gly	glycoproteins	443:455	arg1	glycoproteins					443:455	glycoproteins	443:455	glycoproteins prior to LC-MS analysis	443:479	Efficient protein/glycoprotein extraction is a crucial step in the preparation of N-glycans derived from glycoproteins prior to LC-MS analysis.
29745666	7	64	theme	Efficient	1015:1023	arg1	extraction					1025:1034	Efficient extraction	1015:1034	Efficient extraction of proteins/glycoproteins from biological samples	1015:1084	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	1	65	theme	protein	158:164	arg1	PTM					199:201	PTM	199:201	PTM	199:201	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	65	theme	protein	158:164	arg1	modification					185:196	a common protein post-translational modification	149:196	a common protein post-translational modification (PTM)	149:202	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	65	theme	protein	158:164	arg1	glycosylation					132:144	Protein glycosylation	124:144	Protein glycosylation	124:144	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	4	66	theme	detergent	630:638	arg1	use					583:585	the use	579:585	the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines	579:734	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29745666	1	67	theme	diseases	328:335	arg1	biomarker					310:318	a biomarker	308:318	a biomarker of such diseases	308:335	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	67	theme	diseases	328:335	arg1	PTM					199:201	PTM	199:201	PTM	199:201	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	67	theme	diseases	328:335	arg1	modification					185:196	a common protein post-translational modification	149:196	a common protein post-translational modification (PTM)	149:202	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	67	theme	diseases	328:335	arg1	glycosylation					132:144	Protein glycosylation	124:144	Protein glycosylation	124:144	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	7	68	gly	proteins/glycoproteins	1039:1060	arg1	proteins/glycoproteins					1039:1060	proteins/glycoproteins	1039:1060	proteins/glycoproteins	1039:1060	Efficient extraction of proteins/glycoproteins from biological samples was achieved by combining SDC lysis buffer and beads beating cell disruption.
29745666	1	69	theme	post-translational	166:183	arg1	PTM					199:201	PTM	199:201	PTM	199:201	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	69	theme	post-translational	166:183	arg1	modification					185:196	a common protein post-translational modification	149:196	a common protein post-translational modification (PTM)	149:202	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	1	69	theme	post-translational	166:183	arg1	glycosylation					132:144	Protein glycosylation	124:144	Protein glycosylation	124:144	Protein glycosylation is a common protein post-translational modification (PTM) in living organisms and has been shown to associate with multiple diseases, and thus may potentially be a biomarker of such diseases.
29745666	4	70	theme	labile	623:628	arg1	detergent					630:638	sodium deoxycholate (SDC) acidic labile detergent	590:638	sodium deoxycholate (SDC) acidic labile detergent	590:638	Herein, we evaluated the use of sodium deoxycholate (SDC) acidic labile detergent to release N-glycans of glycoproteins derived from biological samples such as cancer cell lines.
29718541	6	0	gly	N-glycosylated	1081:1094	arg1	mannose					1128:1134	one high mannose	1119:1134	one high mannose	1119:1134	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	0	gly	N-glycosylated	1081:1094	arg1	forms					1096:1100	two differentially N-glycosylated forms	1062:1100	two differentially N-glycosylated forms	1062:1100	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	0	gly	N-glycosylated	1081:1094	arg1	complex					1107:1113	one complex	1103:1113	one complex	1103:1113	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	2	1	theme	GTPase	533:538	arg1	Sar1					540:543	the small GTPase Sar1	523:543	the small GTPase Sar1	523:543	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	4	2	theme	ER-to-Golgi	857:867	arg1	transport					869:877	COPII ER-to-Golgi transport	851:877	COPII ER-to-Golgi transport	851:877	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	7	3	theme	N-glycosylated	1357:1370	arg1	mutants					1377:1383	N-glycosylated Nox5 mutants	1357:1383	N-glycosylated Nox5 mutants	1357:1383	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	1	4	gly	glycoproteins	151:163	arg1	glycoproteins					151:163	Transmembrane glycoproteins	137:163	Transmembrane glycoproteins	137:163	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	2	5	theme	transmembrane	361:373	arg1	Nox5					353:356	the bona fide nonglycoprotein Nox5	323:356	the bona fide nonglycoprotein Nox5	323:356	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	5	theme	transmembrane	361:373	arg1	oxidase					402:408	a transmembrane superoxide-producing NADPH oxidase	359:408	a transmembrane superoxide-producing NADPH oxidase	359:408	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	1	6	theme	Transmembrane	137:149	arg1	glycoproteins					151:163	Transmembrane glycoproteins	137:163	Transmembrane glycoproteins	137:163	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	7	7	from	form	1488:1491	arg1	manner					1515:1520	a Sar1-independent manner	1496:1520	a Sar1-independent manner	1496:1520	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	7	8	theme	Sar1-independent	1498:1513	arg1	manner					1515:1520	a Sar1-independent manner	1496:1520	a Sar1-independent manner	1496:1520	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	7	9	theme	Nox5	1372:1375	arg1	mutants					1377:1383	N-glycosylated Nox5 mutants	1357:1383	N-glycosylated Nox5 mutants	1357:1383	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	6	10	theme	and -independent	1162:1177	arg1	manner					1179:1184	a Sar1/Stx5-dependent and -independent manner	1140:1184	a Sar1/Stx5-dependent and -independent manner	1140:1184	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	1	11	theme	Golgi	233:237	arg1	apparatus					239:247	the Golgi apparatus	229:247	the Golgi apparatus in COPII-coated vesicles en route to the cell surface	229:301	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	3	12	gly	glycoproteins	665:677	arg1	Nox2					714:717	the Nox5-related oxidase Nox2	689:717	the Nox5-related oxidase Nox2	689:717	In contrast, Sar1 (H79G) effectively inhibits ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2.
29718541	3	12	gly	glycoproteins	665:677	arg1	glycoproteins					665:677	glycoproteins	665:677	glycoproteins including the Nox5-related oxidase Nox2	665:717	In contrast, Sar1 (H79G) effectively inhibits ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2.
29718541	6	13	theme	Sar1/Stx5-dependent	1142:1160	arg1	manner					1179:1184	a Sar1/Stx5-dependent and -independent manner	1140:1184	a Sar1/Stx5-dependent and -independent manner	1140:1184	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	2	14	theme	vesicle	565:571	arg1	fission					573:579	COPII vesicle fission	559:579	COPII vesicle fission from the ER	559:591	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	15	gly	nonglycoprotein	337:351	arg1	nonglycoprotein					337:351	the bona fide nonglycoprotein Nox5	323:356	the bona fide nonglycoprotein Nox5	323:356	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	16	theme	COPII	559:563	arg1	fission					573:579	COPII vesicle fission	559:579	COPII vesicle fission from the ER	559:591	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	7	17	theme	plasma	1308:1313	arg1	membrane					1315:1322	the plasma membrane	1304:1322	the plasma membrane	1304:1322	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	2	18	theme	resistant	458:466	arg1	manner					451:456	a manner	449:456	a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER	449:591	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	4	19	dep	sensitive	777:785	arg1	t-SNARE					830:836	a t-SNARE	828:836	a t-SNARE required for COPII ER-to-Golgi transport	828:877	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	19	dep	sensitive	777:785	arg1	trafficking					724:734	The trafficking	720:734	The trafficking of Nox2, but not that of Nox5,	720:765	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	19	dep	sensitive	777:785	arg1	Stx5					821:824	Stx5	821:824	Stx5	821:824	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	19	dep	sensitive	777:785	arg1	sensitive					777:785	sensitive	777:785	sensitive	777:785	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	2	20	theme	nonglycoprotein	337:351	arg1	Nox5					353:356	the bona fide nonglycoprotein Nox5	323:356	the bona fide nonglycoprotein Nox5	323:356	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	20	theme	nonglycoprotein	337:351	arg1	oxidase					402:408	a transmembrane superoxide-producing NADPH oxidase	359:408	a transmembrane superoxide-producing NADPH oxidase	359:408	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	0	21	theme	cell	13:16	arg1	recruitment					26:36	Differential cell surface recruitment	0:36	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.	0:135	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	7	22	theme	Sar1-dependent	1334:1347	arg1	manner					1349:1354	a less Sar1-dependent manner	1327:1354	a less Sar1-dependent manner	1327:1354	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	6	23	theme	cell	1046:1049	arg1	surface					1051:1057	the cell surface	1042:1057	the cell surface	1042:1057	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	2	24	theme	GTP-fixed	503:511	arg1	Sar1					488:491	Sar1	488:491	Sar1 (H79G)	488:498	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	24	theme	GTP-fixed	503:511	arg1	mutant					513:518	a GTP-fixed mutant	501:518	a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER	501:591	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	0	25	theme	Differential	0:11	arg1	recruitment					26:36	Differential cell surface recruitment	0:36	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.	0:135	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	2	26	theme	Sar1	540:543	arg1	Sar1					488:491	Sar1	488:491	Sar1 (H79G)	488:498	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	26	theme	Sar1	540:543	arg1	mutant					513:518	a GTP-fixed mutant	501:518	a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER	501:591	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	4	27	theme	that	753:756	arg1	t-SNARE					830:836	a t-SNARE	828:836	a t-SNARE required for COPII ER-to-Golgi transport	828:877	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	27	theme	that	753:756	arg1	trafficking					724:734	The trafficking	720:734	The trafficking of Nox2, but not that of Nox5,	720:765	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	27	theme	that	753:756	arg1	Stx5					821:824	Stx5	821:824	Stx5	821:824	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	27	theme	that	753:756	arg1	sensitive					777:785	sensitive	777:785	sensitive	777:785	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	2	28	theme	bona	327:330	arg1	Nox5					353:356	the bona fide nonglycoprotein Nox5	323:356	the bona fide nonglycoprotein Nox5	323:356	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	28	theme	bona	327:330	arg1	oxidase					402:408	a transmembrane superoxide-producing NADPH oxidase	359:408	a transmembrane superoxide-producing NADPH oxidase	359:408	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	1	29	theme	COPII-coated	252:263	arg1	vesicles					265:272	COPII-coated vesicles	252:272	COPII-coated vesicles en route to the cell surface	252:301	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	7	30	gly	N-glycosylated	1357:1370	arg1	mutants					1377:1383	N-glycosylated Nox5 mutants	1357:1383	N-glycosylated Nox5 mutants	1357:1383	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	6	31	theme	high	1123:1126	arg1	mannose					1128:1134	one high mannose	1119:1134	one high mannose	1119:1134	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	31	theme	high	1123:1126	arg1	forms					1096:1100	two differentially N-glycosylated forms	1062:1100	two differentially N-glycosylated forms	1062:1100	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	2	32	theme	superoxide-producing	375:394	arg1	Nox5					353:356	the bona fide nonglycoprotein Nox5	323:356	the bona fide nonglycoprotein Nox5	323:356	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	32	theme	superoxide-producing	375:394	arg1	oxidase					402:408	a transmembrane superoxide-producing NADPH oxidase	359:408	a transmembrane superoxide-producing NADPH oxidase	359:408	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	33	theme	NADPH	396:400	arg1	Nox5					353:356	the bona fide nonglycoprotein Nox5	323:356	the bona fide nonglycoprotein Nox5	323:356	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	2	33	theme	NADPH	396:400	arg1	oxidase					402:408	a transmembrane superoxide-producing NADPH oxidase	359:408	a transmembrane superoxide-producing NADPH oxidase	359:408	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	3	34	theme	ER-to-Golgi	640:650	arg1	transport					652:660	ER-to-Golgi transport	640:660	ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2	640:717	In contrast, Sar1 (H79G) effectively inhibits ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2.
29718541	1	35	from	apparatus	239:247	arg1	vesicles					265:272	COPII-coated vesicles	252:272	COPII-coated vesicles en route to the cell surface	252:301	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	0	36	dep	oxidases	72:79	arg1	Nox5					96:99	Nox5	96:99	Nox5	96:99	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	36	dep	oxidases	72:79	arg1	oxidases					72:79	the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5	41:99	the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5	41:99	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	36	dep	oxidases	72:79	arg1	Nox2					87:90	Nox2	87:90	Nox2	87:90	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	36	dep	oxidases	72:79	arg1	Nox1					81:84	Nox1	81:84	Nox1	81:84	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	1	37	theme	endoplasmic	185:195	arg1	ER					208:209	ER	208:209	ER	208:209	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	1	37	theme	endoplasmic	185:195	arg1	reticulum					197:205	the endoplasmic reticulum	181:205	the endoplasmic reticulum (ER)	181:210	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	2	38	theme	cell	433:436	arg1	surface					438:444	the cell surface	429:444	the cell surface	429:444	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	0	39	theme	small	118:122	arg1	Sar1					131:134	the small GTPase Sar1	114:134	the small GTPase Sar1	114:134	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	7	40	theme	complex	1423:1429	arg1	surface					1400:1406	the cell surface	1391:1406	the cell surface	1391:1406	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	7	40	theme	complex	1423:1429	arg1	Sar1-dependently					1436:1451	the complex form Sar1-dependently	1419:1451	the complex form Sar1-dependently	1419:1451	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	4	41	theme	Nox2	739:742	arg1	t-SNARE					830:836	a t-SNARE	828:836	a t-SNARE required for COPII ER-to-Golgi transport	828:877	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	41	theme	Nox2	739:742	arg1	trafficking					724:734	The trafficking	720:734	The trafficking of Nox2, but not that of Nox5,	720:765	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	41	theme	Nox2	739:742	arg1	Stx5					821:824	Stx5	821:824	Stx5	821:824	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	4	41	theme	Nox2	739:742	arg1	sensitive					777:785	sensitive	777:785	sensitive	777:785	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	6	42	theme	N-glycosylated	1081:1094	arg1	mannose					1128:1134	one high mannose	1119:1134	one high mannose	1119:1134	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	42	theme	N-glycosylated	1081:1094	arg1	forms					1096:1100	two differentially N-glycosylated forms	1062:1100	two differentially N-glycosylated forms	1062:1100	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	42	theme	N-glycosylated	1081:1094	arg1	complex					1107:1113	one complex	1103:1113	one complex	1103:1113	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	2	43	theme	small	527:531	arg1	Sar1					540:543	the small GTPase Sar1	523:543	the small GTPase Sar1	523:543	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	3	44	theme	Nox5-related	693:704	arg1	Nox2					714:717	the Nox5-related oxidase Nox2	689:717	the Nox5-related oxidase Nox2	689:717	In contrast, Sar1 (H79G) effectively inhibits ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2.
29718541	2	45	theme	Sar1	488:491	arg1	co-expression					471:483	co-expression	471:483	co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER	471:591	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	0	46	theme	NADPH	66:70	arg1	Nox5					96:99	Nox5	96:99	Nox5	96:99	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	46	theme	NADPH	66:70	arg1	oxidases					72:79	the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5	41:99	the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5	41:99	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	46	theme	NADPH	66:70	arg1	Nox2					87:90	Nox2	87:90	Nox2	87:90	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	46	theme	NADPH	66:70	arg1	Nox1					81:84	Nox1	81:84	Nox1	81:84	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	3	47	theme	oxidase	706:712	arg1	Nox2					714:717	the Nox5-related oxidase Nox2	689:717	the Nox5-related oxidase Nox2	689:717	In contrast, Sar1 (H79G) effectively inhibits ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2.
29718541	0	48	theme	Sar1	131:134	arg1	role					106:109	The role	102:109	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.	0:135	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	3	49	theme	glycoproteins	665:677	arg1	transport					652:660	ER-to-Golgi transport	640:660	ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2	640:717	In contrast, Sar1 (H79G) effectively inhibits ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2.
29718541	7	50	theme	glycosylation-defective	1245:1267	arg1	Nox2					1276:1279	a glycosylation-defective mutant Nox2	1243:1279	a glycosylation-defective mutant Nox2	1243:1279	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	6	51	theme	Nox1	1004:1007	arg1	trafficking					1009:1019	Nox1 trafficking	1004:1019	Nox1 trafficking	1004:1019	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	52	theme	Nox1	1025:1028	arg1	advances					1030:1037	Nox1 advances	1025:1037	Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose	1025:1134	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	0	53	theme	superoxide-producing	45:64	arg1	Nox5					96:99	Nox5	96:99	Nox5	96:99	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	53	theme	superoxide-producing	45:64	arg1	oxidases					72:79	the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5	41:99	the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5	41:99	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	53	theme	superoxide-producing	45:64	arg1	Nox2					87:90	Nox2	87:90	Nox2	87:90	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	53	theme	superoxide-producing	45:64	arg1	Nox1					81:84	Nox1	81:84	Nox1	81:84	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	54	theme	GTPase	124:129	arg1	Sar1					131:134	the small GTPase Sar1	114:134	the small GTPase Sar1	114:134	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	7	55	theme	mutant	1269:1274	arg1	Nox2					1276:1279	a glycosylation-defective mutant Nox2	1243:1279	a glycosylation-defective mutant Nox2	1243:1279	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	1	56	theme	cell	290:293	arg1	surface					295:301	the cell surface	286:301	the cell surface	286:301	Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface.
29718541	4	57	theme	syntaxin	809:816	arg1	over-expression					790:804	over-expression	790:804	over-expression of syntaxin 5	790:818	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	0	58	dep	recruitment	26:36	arg1	role					106:109	The role	102:109	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.	0:135	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	5	59	theme	Sar1/Stx5-dependent	923:941	arg1	pathways					960:967	the Sar1/Stx5-dependent and -independent pathways	919:967	the Sar1/Stx5-dependent and -independent pathways	919:967	Thus, Nox2 and Nox5 mainly traffic via the Sar1/Stx5-dependent and -independent pathways, respectively.
29718541	2	60	dep	bona	327:330	arg1	fide					332:335	fide	332:335	fide	332:335	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	7	61	theme	form	1431:1434	arg1	surface					1400:1406	the cell surface	1391:1406	the cell surface	1391:1406	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	7	61	theme	form	1431:1434	arg1	Sar1-dependently					1436:1451	the complex form Sar1-dependently	1419:1451	the complex form Sar1-dependently	1419:1451	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	6	62	from	advances	1030:1037	arg1	mannose					1128:1134	one high mannose	1119:1134	one high mannose	1119:1134	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	62	from	advances	1030:1037	arg1	forms					1096:1100	two differentially N-glycosylated forms	1062:1100	two differentially N-glycosylated forms	1062:1100	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	6	62	from	advances	1030:1037	arg1	complex					1107:1113	one complex	1103:1113	one complex	1103:1113	Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively.
29718541	7	63	theme	high-mannose	1475:1486	arg1	surface					1400:1406	the cell surface	1391:1406	the cell surface	1391:1406	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	7	63	theme	high-mannose	1475:1486	arg1	form					1488:1491	the high-mannose form	1471:1491	the high-mannose form in a Sar1-independent manner	1471:1520	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	4	64	theme	COPII	851:855	arg1	transport					869:877	COPII ER-to-Golgi transport	851:877	COPII ER-to-Golgi transport	851:877	The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport.
29718541	5	65	theme	and -independent	943:958	arg1	pathways					960:967	the Sar1/Stx5-dependent and -independent pathways	919:967	the Sar1/Stx5-dependent and -independent pathways	919:967	Thus, Nox2 and Nox5 mainly traffic via the Sar1/Stx5-dependent and -independent pathways, respectively.
29718541	2	66	from	ER	590:591	arg1	fission					573:579	COPII vesicle fission	559:579	COPII vesicle fission from the ER	559:591	Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER.
29718541	0	67	theme	oxidases	72:79	arg1	recruitment					26:36	Differential cell surface recruitment	0:36	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.	0:135	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	0	68	theme	surface	18:24	arg1	recruitment					26:36	Differential cell surface recruitment	0:36	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.	0:135	Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1.
29718541	7	69	theme	cell	1395:1398	arg1	surface					1400:1406	the cell surface	1391:1406	the cell surface	1391:1406	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	7	69	theme	cell	1395:1398	arg1	form					1488:1491	the high-mannose form	1471:1491	the high-mannose form in a Sar1-independent manner	1471:1520	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
29718541	7	69	theme	cell	1395:1398	arg1	Sar1-dependently					1436:1451	the complex form Sar1-dependently	1419:1451	the complex form Sar1-dependently	1419:1451	Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner.
30637162	0	0	theme	adenosine	79:87	arg1	kinase					121:126	adenosine monophosphate-activated protein kinase	79:126	adenosine monophosphate-activated protein kinase	79:126	Quercetin induces cell death in cervical cancer by reducing O-GlcNAcylation of adenosine monophosphate-activated protein kinase.
30637162	5	1	theme	transferase-mediated	756:775	arg1	labelling					812:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	7	2	theme	O-linked	1042:1049	arg1	OGT					1084:1086	OGT	1084:1086	OGT	1084:1086	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	2	theme	O-linked	1042:1049	arg1	transferase					1071:1081	O-linked N-acetylglucosamine transferase	1042:1081	O-linked N-acetylglucosamine transferase (OGT)	1042:1087	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	1	3	theme	cancer	175:180	arg1	Hyper-O-GlcNAcylation					129:149	Hyper-O-GlcNAcylation	129:149	Hyper-O-GlcNAcylation	129:149	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	1	3	theme	cancer	175:180	arg1	feature					164:170	a general feature	154:170	a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth	154:273	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	4	4	theme	anticancer	579:588	arg1	effect					590:595	the anticancer effect	575:595	the anticancer effect of quercetin on HeLa cells	575:622	The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells.
30637162	5	5	theme	deoxyuridine	777:788	arg1	labelling					812:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	5	6	theme	triphosphate	790:801	arg1	labelling					812:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	8	7	from	effect	1219:1224	arg1	cells					1235:1239	HaCaT cells	1229:1239	HaCaT cells	1229:1239	Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells.
30637162	3	8	from	effect	507:512	arg1	O-GlcNAcylation					517:531	O-GlcNAcylation	517:531	O-GlcNAcylation	517:531	Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation.
30637162	0	9	theme	protein	113:119	arg1	kinase					121:126	adenosine monophosphate-activated protein kinase	79:126	adenosine monophosphate-activated protein kinase	79:126	Quercetin induces cell death in cervical cancer by reducing O-GlcNAcylation of adenosine monophosphate-activated protein kinase.
30637162	13	10	theme	SREBP-1	1804:1810	arg1	immunoreactivities					1774:1791	the immunoreactivities	1770:1791	the immunoreactivities of OGT and SREBP-1 in HeLa cells	1770:1824	Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells.
30637162	8	11	theme	HeLa	1264:1267	arg1	cells					1269:1273	HeLa cells	1264:1273	HeLa cells	1264:1273	Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells.
30637162	13	12	theme	immunofluorescence	1700:1717	arg1	staining					1719:1726	immunofluorescence staining	1700:1726	immunofluorescence staining	1700:1726	Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells.
30637162	0	13	theme	monophosphate-activated	89:111	arg1	kinase					121:126	adenosine monophosphate-activated protein kinase	79:126	adenosine monophosphate-activated protein kinase	79:126	Quercetin induces cell death in cervical cancer by reducing O-GlcNAcylation of adenosine monophosphate-activated protein kinase.
30637162	14	14	theme	AMPK	1936:1939	arg1	O-GlcNAcylation					1917:1931	the O-GlcNAcylation	1913:1931	the O-GlcNAcylation of AMPK	1913:1939	Our findings demonstrate that quercetin exhibited its anticancer effect by decreasing the O-GlcNAcylation of AMPK.
30637162	10	15	theme	global	1382:1387	arg1	O-GlcNAcylation					1389:1403	global O-GlcNAcylation	1382:1403	global O-GlcNAcylation	1382:1403	Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK.
30637162	2	16	theme	dietary	309:315	arg1	Quercetin					276:284	Quercetin	276:284	Quercetin	276:284	Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer.
30637162	2	16	theme	dietary	309:315	arg1	flavonoid					317:325	a naturally occurring dietary flavonoid	287:325	a naturally occurring dietary flavonoid	287:325	Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer.
30637162	15	17	theme	Further	1942:1948	arg1	studies					1950:1956	Further studies	1942:1956	Further studies	1942:1956	Further studies are needed to explore how quercetin regulates O-GlcNAcylation in cancer.
30637162	8	18	theme	cell	1199:1202	arg1	death					1204:1208	cell death	1199:1208	cell death	1199:1208	Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells.
30637162	5	19	theme	MTT	722:724	arg1	assays					822:827	MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays	722:827	MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays	722:827	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	6	20	theme	germ	920:923	arg1	agglutinin					925:934	succinylated wheat germ agglutinin pulldown and immunoprecipitation	901:967	succinylated wheat germ agglutinin pulldown and immunoprecipitation	901:967	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	14	21	theme	anticancer	1881:1890	arg1	effect					1892:1897	its anticancer effect	1877:1897	its anticancer effect	1877:1897	Our findings demonstrate that quercetin exhibited its anticancer effect by decreasing the O-GlcNAcylation of AMPK.
30637162	2	22	theme	occurring	299:307	arg1	Quercetin					276:284	Quercetin	276:284	Quercetin	276:284	Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer.
30637162	2	22	theme	occurring	299:307	arg1	flavonoid					317:325	a naturally occurring dietary flavonoid	287:325	a naturally occurring dietary flavonoid	287:325	Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer.
30637162	3	23	theme	quercetin	440:448	arg1	effect					430:435	the anticancer effect	415:435	the anticancer effect of quercetin	415:448	Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation.
30637162	0	24	theme	kinase	121:126	arg1	O-GlcNAcylation					60:74	O-GlcNAcylation	60:74	O-GlcNAcylation of adenosine monophosphate-activated protein kinase	60:126	Quercetin induces cell death in cervical cancer by reducing O-GlcNAcylation of adenosine monophosphate-activated protein kinase.
30637162	6	25	theme	wheat	914:918	arg1	agglutinin					925:934	succinylated wheat germ agglutinin pulldown and immunoprecipitation	901:967	succinylated wheat germ agglutinin pulldown and immunoprecipitation	901:967	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	0	26	theme	cervical	32:39	arg1	cancer					41:46	cervical cancer	32:46	cervical cancer	32:46	Quercetin induces cell death in cervical cancer by reducing O-GlcNAcylation of adenosine monophosphate-activated protein kinase.
30637162	9	27	theme	HeLa	1312:1315	arg1	cells					1317:1321	HeLa cells	1312:1321	HeLa cells	1312:1321	O-GlcNAcylation level was higher in HeLa cells than in HaCaT cells.
30637162	4	28	from	effect	650:655	arg1	cells					666:670	HaCaT cells	660:670	HaCaT cells	660:670	The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells.
30637162	8	29	theme	HaCaT	1229:1233	arg1	cells					1235:1239	HaCaT cells	1229:1239	HaCaT cells	1229:1239	Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells.
30637162	13	30	theme	quercetin	1740:1748	arg1	treatment					1750:1758	quercetin treatment	1740:1758	quercetin treatment	1740:1758	Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells.
30637162	6	31	theme	succinylated	901:912	arg1	agglutinin					925:934	succinylated wheat germ agglutinin pulldown and immunoprecipitation	901:967	succinylated wheat germ agglutinin pulldown and immunoprecipitation	901:967	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	8	32	theme	cell	1168:1171	arg1	proliferation					1173:1185	cell proliferation	1168:1185	cell proliferation	1168:1185	Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells.
30637162	4	33	theme	HaCaT	660:664	arg1	cells					666:670	HaCaT cells	660:670	HaCaT cells	660:670	The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells.
30637162	9	34	theme	HaCaT	1331:1335	arg1	cells					1337:1341	HaCaT cells	1331:1341	HaCaT cells	1331:1341	O-GlcNAcylation level was higher in HeLa cells than in HaCaT cells.
30637162	13	35	theme	HeLa	1815:1818	arg1	cells					1820:1824	HeLa cells	1815:1824	HeLa cells	1815:1824	Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells.
30637162	7	36	theme	Immunofluorescence	970:987	arg1	staining					989:996	Immunofluorescence staining	970:996	Immunofluorescence staining	970:996	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	11	37	theme	AMPK	1526:1529	arg1	O-GlcNAcylation					1507:1521	reduced O-GlcNAcylation	1499:1521	reduced O-GlcNAcylation of AMPK	1499:1529	AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine.
30637162	1	38	theme	cancer	211:216	arg1	proliferation					245:257	cell proliferation	240:257	cell proliferation	240:257	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	1	38	theme	cancer	211:216	arg1	growth					268:273	cell growth	263:273	cell growth	263:273	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	1	38	theme	cancer	211:216	arg1	phenotypes					218:227	various cancer phenotypes	203:227	various cancer phenotypes	203:227	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	4	39	theme	study	550:554	arg1	aim					538:540	The aim	534:540	The aim of this study	534:554	The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells.
30637162	11	40	with	treatment	1548:1556	arg1	6-diazo-5-oxo-L-norleucine					1563:1588	6-diazo-5-oxo-L-norleucine	1563:1588	6-diazo-5-oxo-L-norleucine	1563:1588	AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine.
30637162	6	41	theme	AMP-activated	849:861	arg1	AMPK					879:882	AMPK	879:882	AMPK	879:882	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	6	41	theme	AMP-activated	849:861	arg1	kinase					871:876	AMP-activated protein kinase	849:876	AMP-activated protein kinase (AMPK)	849:883	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	1	42	theme	various	203:209	arg1	proliferation					245:257	cell proliferation	240:257	cell proliferation	240:257	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	1	42	theme	various	203:209	arg1	growth					268:273	cell growth	263:273	cell growth	263:273	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	1	42	theme	various	203:209	arg1	phenotypes					218:227	various cancer phenotypes	203:227	various cancer phenotypes	203:227	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	5	43	theme	cell	692:695	arg1	death					697:701	cell death	692:701	cell death	692:701	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	11	44	theme	AMPK	1476:1479	arg1	activation					1481:1490	AMPK activation	1476:1490	AMPK activation due to reduced O-GlcNAcylation of AMPK	1476:1529	AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine.
30637162	7	45	used	used	1002:1005	arg2	staining					989:996	Immunofluorescence staining	970:996	Immunofluorescence staining	970:996	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	3	46	theme	effect	430:435	arg1	reports					404:410	Several reports	396:410	Several reports of the anticancer effect of quercetin	396:448	Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation.
30637162	11	47	theme	reduced	1499:1505	arg1	O-GlcNAcylation					1507:1521	reduced O-GlcNAcylation	1499:1521	reduced O-GlcNAcylation of AMPK	1499:1529	AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine.
30637162	7	48	theme	protein	1127:1133	arg1	immunoreactivitiy					1021:1037	the immunoreactivitiy	1017:1037	the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1)	1017:1145	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	9	49	theme	O-GlcNAcylation	1276:1290	arg1	level					1292:1296	O-GlcNAcylation level	1276:1296	O-GlcNAcylation level	1276:1296	O-GlcNAcylation level was higher in HeLa cells than in HaCaT cells.
30637162	0	50	theme	cell	18:21	arg1	death					23:27	cell death	18:27	cell death	18:27	Quercetin induces cell death in cervical cancer by reducing O-GlcNAcylation of adenosine monophosphate-activated protein kinase.
30637162	5	51	theme	nick-end	803:810	arg1	labelling					812:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	4	52	from	effect	590:595	arg1	cells					618:622	HeLa cells	613:622	HeLa cells	613:622	The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells.
30637162	6	53	dep	agglutinin	925:934	arg1	immunoprecipitation					949:967	immunoprecipitation	949:967	immunoprecipitation	949:967	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	6	53	dep	agglutinin	925:934	arg1	pulldown					936:943	pulldown	936:943	pulldown	936:943	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	10	54	theme	O-GlcNAcylation	1389:1403	arg1	expression					1368:1377	the expression	1364:1377	the expression of global O-GlcNAcylation	1364:1403	Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK.
30637162	1	55	theme	cell	240:243	arg1	proliferation					245:257	cell proliferation	240:257	cell proliferation	240:257	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	5	56	theme	labelling	812:820	arg1	assays					822:827	MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays	722:827	MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays	722:827	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	12	57	theme	transcriptional	1662:1676	arg1	targets					1678:1684	its transcriptional targets	1658:1684	its transcriptional targets	1658:1684	Our results also demonstrated that quercetin regulated SREBP-1 and its transcriptional targets.
30637162	7	58	theme	element	1111:1117	arg1	protein					1127:1133	sterol regulatory element binding protein 1	1093:1135	sterol regulatory element binding protein 1 (SREBP-1)	1093:1145	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	58	theme	element	1111:1117	arg1	SREBP-1					1138:1144	SREBP-1	1138:1144	SREBP-1	1138:1144	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	59	link	O-linked	1042:1049	arg1	OGT					1084:1086	OGT	1084:1086	OGT	1084:1086	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	59	link	O-linked	1042:1049	arg1	transferase					1071:1081	O-linked N-acetylglucosamine transferase	1042:1081	O-linked N-acetylglucosamine transferase (OGT)	1042:1087	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	60	theme	sterol	1093:1098	arg1	protein					1127:1133	sterol regulatory element binding protein 1	1093:1135	sterol regulatory element binding protein 1 (SREBP-1)	1093:1145	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	60	theme	sterol	1093:1098	arg1	SREBP-1					1138:1144	SREBP-1	1138:1144	SREBP-1	1138:1144	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	3	61	theme	anticancer	419:428	arg1	effect					430:435	the anticancer effect	415:435	the anticancer effect of quercetin	415:448	Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation.
30637162	13	62	theme	OGT	1796:1798	arg1	immunoreactivities					1774:1791	the immunoreactivities	1770:1791	the immunoreactivities of OGT and SREBP-1 in HeLa cells	1770:1824	Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells.
30637162	7	63	theme	binding	1119:1125	arg1	protein					1127:1133	sterol regulatory element binding protein 1	1093:1135	sterol regulatory element binding protein 1 (SREBP-1)	1093:1145	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	63	theme	binding	1119:1125	arg1	SREBP-1					1138:1144	SREBP-1	1138:1144	SREBP-1	1138:1144	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	10	64	theme	AMPK	1470:1473	arg1	O-GlcNAcylation					1451:1465	the O-GlcNAcylation	1447:1465	the O-GlcNAcylation of AMPK	1447:1473	Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK.
30637162	10	65	theme	AMPK	1419:1422	arg1	activation					1424:1433	AMPK activation	1419:1433	AMPK activation	1419:1433	Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK.
30637162	5	66	theme	Cell	673:676	arg1	viability					678:686	Cell viability	673:686	Cell viability	673:686	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	7	67	theme	regulatory	1100:1109	arg1	protein					1127:1133	sterol regulatory element binding protein 1	1093:1135	sterol regulatory element binding protein 1 (SREBP-1)	1093:1145	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	67	theme	regulatory	1100:1109	arg1	SREBP-1					1138:1144	SREBP-1	1138:1144	SREBP-1	1138:1144	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	6	68	theme	kinase	871:876	arg1	O-GlcNAcylation					830:844	O-GlcNAcylation	830:844	O-GlcNAcylation of AMP-activated protein kinase (AMPK)	830:883	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	7	69	theme	N-acetylglucosamine	1051:1069	arg1	OGT					1084:1086	OGT	1084:1086	OGT	1084:1086	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	7	69	theme	N-acetylglucosamine	1051:1069	arg1	transferase					1071:1081	O-linked N-acetylglucosamine transferase	1042:1081	O-linked N-acetylglucosamine transferase (OGT)	1042:1087	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	1	70	theme	general	156:162	arg1	Hyper-O-GlcNAcylation					129:149	Hyper-O-GlcNAcylation	129:149	Hyper-O-GlcNAcylation	129:149	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	1	70	theme	general	156:162	arg1	feature					164:170	a general feature	154:170	a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth	154:273	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	13	71	from	immunoreactivities	1774:1791	arg1	cells					1820:1824	HeLa cells	1815:1824	HeLa cells	1815:1824	Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells.
30637162	4	72	theme	quercetin	600:608	arg1	effect					590:595	the anticancer effect	575:595	the anticancer effect of quercetin on HeLa cells	575:622	The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells.
30637162	5	73	theme	terminal	730:737	arg1	labelling					812:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	6	74	theme	protein	863:869	arg1	AMPK					879:882	AMPK	879:882	AMPK	879:882	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	6	74	theme	protein	863:869	arg1	kinase					871:876	AMP-activated protein kinase	849:876	AMP-activated protein kinase (AMPK)	849:883	O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation.
30637162	7	75	theme	transferase	1071:1081	arg1	immunoreactivitiy					1021:1037	the immunoreactivitiy	1017:1037	the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1)	1017:1145	Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1).
30637162	2	76	theme	cancer	388:393	arg1	growth					378:383	growth	378:383	growth	378:383	Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer.
30637162	2	76	theme	cancer	388:393	arg1	proliferation					360:372	proliferation	360:372	proliferation	360:372	Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer.
30637162	1	77	theme	cell	263:266	arg1	growth					268:273	cell growth	263:273	cell growth	263:273	Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth.
30637162	5	78	theme	deoxynucleotidyl	739:754	arg1	labelling					812:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling	730:820	Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays.
30637162	3	79	theme	Several	396:402	arg1	reports					404:410	Several reports	396:410	Several reports of the anticancer effect of quercetin	396:448	Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation.
30637162	4	80	theme	HeLa	613:616	arg1	cells					618:622	HeLa cells	613:622	HeLa cells	613:622	The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells.
30328115	9	0	theme	postnatal	1187:1195	arg1	ages					1197:1200	postnatal ages	1187:1200	postnatal ages	1187:1200	At postnatal ages, Nrg3 was abundantly expressed throughout the cerebral cortex and hippocampus.
30328115	13	1	theme	other	1684:1688	arg1	members					1701:1707	the other Nrg family members	1680:1707	the other Nrg family members	1680:1707	These findings suggest that Nrg3 plays roles that are distinct from the other Nrg family members.
30328115	6	2	from	expression	931:940	arg1	glia					945:948	glia	945:948	glia	945:948	Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited.
30328115	3	3	theme	RNA	419:421	arg1	levels					435:440	both the RNA and protein levels	410:440	levels	435:440	To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels.
30328115	5	4	theme	transfected	670:680	arg1	cells					690:694	transfected Neuro2a cells	670:694	transfected Neuro2a cells	670:694	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	4	5	from	increase	513:520	arg1	stages					564:569	embryonic stages	554:569	embryonic stages to adulthood	554:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	0	6	from	expression	14:23	arg1	system					68:73	the rat central nervous system	44:73	the rat central nervous system	44:73	Developmental expression of Neuregulin-3 in the rat central nervous system.
30328115	1	7	theme	growth	129:134	arg1	factors					136:142	growth factors	129:142	growth factors identified as risk factors for schizophrenia	129:187	Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia.
30328115	6	8	theme	inhibitory	906:915	arg1	neurons					917:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited.
30328115	5	9	theme	neuronal	651:658	arg1	cultures					660:667	cortical neuronal cultures	642:667	cortical neuronal cultures	642:667	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	7	10	theme	embryonic	1019:1027	arg1	ages					1043:1046	both embryonic and postnatal ages	1014:1046	both embryonic and postnatal ages	1014:1046	Nrg3 mRNA and protein were widely expressed during both embryonic and postnatal ages.
30328115	11	11	theme	Purkinje	1409:1416	arg1	cells					1418:1422	Purkinje cells	1409:1422	Purkinje cells	1409:1422	In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons.
30328115	4	12	theme	developmental	499:511	arg1	increase					513:520	a developmental increase	497:520	a developmental increase of Nrg3 protein expression from embryonic stages to adulthood	497:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	4	13	theme	expression	538:547	arg1	increase					513:520	a developmental increase	497:520	a developmental increase of Nrg3 protein expression from embryonic stages to adulthood	497:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	13	14	theme	family	1694:1699	arg1	members					1701:1707	the other Nrg family members	1680:1707	the other Nrg family members	1680:1707	These findings suggest that Nrg3 plays roles that are distinct from the other Nrg family members.
30328115	11	15	theme	granule	1428:1434	arg1	neurons					1436:1442	granule neurons	1428:1442	granule neurons	1428:1442	In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons.
30328115	4	16	theme	O-linked	615:622	arg1	carbohydrates					624:636	O-linked carbohydrates	615:636	O-linked carbohydrates	615:636	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	12	17	theme	expression	1536:1545	arg1	patterns					1524:1531	its patterns	1520:1531	its patterns of expression	1520:1545	In the rodent brain, Nrg3 is the most abundantly expressed of the Nrgs and its patterns of expression differ both temporally and spatially from that of Nrg1 and Nrg2.
30328115	11	18	located	found	1395:1399	arg2	Nrg3					1386:1389	Nrg3	1386:1389	Nrg3	1386:1389	In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons.
30328115	11	18	located	found	1395:1399	arg1	cerebellum					1374:1383	the cerebellum	1370:1383	the cerebellum	1370:1383	In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons.
30328115	11	18	located	found	1395:1399	arg1	neurons					1436:1442	granule neurons	1428:1442	granule neurons	1428:1442	In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons.
30328115	11	18	located	found	1395:1399	arg1	cells					1418:1422	Purkinje cells	1409:1422	Purkinje cells	1409:1422	In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons.
30328115	3	19	from	levels	435:440	arg1	expression					379:388	its expression	375:388	its expression in the rat brain at both the RNA and protein levels	375:440	To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels.
30328115	1	20	theme	factors	136:142	arg1	family					119:124	the Nrg family	111:124	the Nrg family of growth factors identified as risk factors for schizophrenia	111:187	Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia.
30328115	5	21	theme	Nrg3	723:726	arg1	protein					728:734	Nrg3 protein	723:734	Nrg3 protein	723:734	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	8	22	theme	cortical	1086:1093	arg1	plate					1095:1099	cortical plate	1086:1099	cortical plate	1086:1099	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	13	23	theme	Nrg	1690:1692	arg1	members					1701:1707	the other Nrg family members	1680:1707	the other Nrg family members	1680:1707	These findings suggest that Nrg3 plays roles that are distinct from the other Nrg family members.
30328115	4	24	link	O-linked	615:622	arg1	carbohydrates					624:636	O-linked carbohydrates	615:636	O-linked carbohydrates	615:636	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	8	25	dep	plate	1095:1099	arg1	the					1082:1084	the	1082:1084	the	1082:1084	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	0	26	theme	Developmental	0:12	arg1	expression					14:23	Developmental expression	0:23	Developmental expression of Neuregulin-3 in the rat central nervous system.	0:74	Developmental expression of Neuregulin-3 in the rat central nervous system.
30328115	6	27	theme	GABAergic	869:877	arg1	neurons					917:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited.
30328115	8	28	dep	cell	1151:1154	arg1	proliferation					1156:1168	proliferation	1156:1168	proliferation	1156:1168	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	4	29	from	stages	564:569	arg1	expression					538:547	Nrg3 protein expression	525:547	Nrg3 protein expression from embryonic stages to adulthood	525:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	4	29	from	stages	564:569	arg1	increase					513:520	a developmental increase	497:520	a developmental increase of Nrg3 protein expression from embryonic stages to adulthood	497:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	1	30	theme	risk	158:161	arg1	factors					163:169	risk factors	158:169	risk factors for schizophrenia	158:187	Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia.
30328115	0	31	theme	Neuregulin-3	28:39	arg1	expression					14:23	Developmental expression	0:23	Developmental expression of Neuregulin-3 in the rat central nervous system.	0:74	Developmental expression of Neuregulin-3 in the rat central nervous system.
30328115	9	32	theme	cerebral	1248:1255	arg1	cortex					1257:1262	the cerebral cortex	1244:1262	the cerebral cortex	1244:1262	At postnatal ages, Nrg3 was abundantly expressed throughout the cerebral cortex and hippocampus.
30328115	7	33	theme	postnatal	1033:1041	arg1	ages					1043:1046	both embryonic and postnatal ages	1014:1046	both embryonic and postnatal ages	1014:1046	Nrg3 mRNA and protein were widely expressed during both embryonic and postnatal ages.
30328115	5	34	located	localized	740:748	arg1	sections					714:721	brain tissue sections	701:721	brain tissue sections	701:721	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	5	34	located	localized	740:748	arg1	cells					690:694	transfected Neuro2a cells	670:694	transfected Neuro2a cells	670:694	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	5	34	located	localized	740:748	arg1	cultures					660:667	cortical neuronal cultures	642:667	cortical neuronal cultures	642:667	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	5	34	located	localized	740:748	arg2	protein					728:734	Nrg3 protein	723:734	Nrg3 protein	723:734	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	8	35	located	detected	1066:1073	arg1	E17					1052:1054	E17	1052:1054	E17	1052:1054	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	8	35	located	detected	1066:1073	arg1	plate					1095:1099	cortical plate	1086:1099	cortical plate	1086:1099	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	8	35	located	detected	1066:1073	arg2	Nrg3					1057:1060	Nrg3	1057:1060	Nrg3	1057:1060	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	8	35	located	detected	1066:1073	arg1	zone					1117:1120	ventricular zone	1105:1120	ventricular zone	1105:1120	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	12	36	theme	rodent	1452:1457	arg1	brain					1459:1463	the rodent brain	1448:1463	the rodent brain	1448:1463	In the rodent brain, Nrg3 is the most abundantly expressed of the Nrgs and its patterns of expression differ both temporally and spatially from that of Nrg1 and Nrg2.
30328115	6	37	theme	excitatory	857:866	arg1	neurons					917:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited.
30328115	5	38	dep	apparatus	790:798	arg1	expressed					825:833	expressed	825:833	is prominently expressed	810:833	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	1	39	theme	Nrg	115:117	arg1	family					119:124	the Nrg family	111:124	the Nrg family of growth factors identified as risk factors for schizophrenia	111:187	Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia.
30328115	5	40	theme	brain	701:705	arg1	sections					714:721	brain tissue sections	701:721	brain tissue sections	701:721	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	2	41	dep	Nrgs	206:209	arg1	characterized					288:300	characterized	288:300	characterized	288:300	There are three Nrgs expressed in the nervous system (Nrg1-3) and of these Nrg1 has been the best characterized.
30328115	5	42	theme	tissue	707:712	arg1	sections					714:721	brain tissue sections	701:721	brain tissue sections	701:721	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	5	43	theme	cortical	642:649	arg1	cultures					660:667	cortical neuronal cultures	642:667	cortical neuronal cultures	642:667	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	6	44	located	detected	845:852	arg1	neurons					917:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited.
30328115	6	44	located	detected	845:852	arg2	Nrg3					836:839	Nrg3	836:839	Nrg3	836:839	Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited.
30328115	3	45	from	expression	379:388	arg1	brain					401:405	the rat brain	393:405	the rat brain	393:405	To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels.
30328115	4	46	theme	embryonic	554:562	arg1	stages					564:569	embryonic stages	554:569	embryonic stages to adulthood	554:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	3	47	theme	neural	341:346	arg1	roles					348:352	neural roles	341:352	neural roles for Nrg3	341:361	To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels.
30328115	5	48	theme	Golgi	784:788	arg1	apparatus					790:798	the Golgi apparatus	780:798	the Golgi apparatus	780:798	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	8	49	theme	ventricular	1105:1115	arg1	zone					1117:1120	ventricular zone	1105:1120	ventricular zone	1105:1120	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	0	50	theme	nervous	60:66	arg1	system					68:73	the rat central nervous system	44:73	the rat central nervous system	44:73	Developmental expression of Neuregulin-3 in the rat central nervous system.
30328115	3	51	theme	rat	397:399	arg1	brain					401:405	the rat brain	393:405	the rat brain	393:405	To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels.
30328115	0	52	theme	rat	48:50	arg1	system					68:73	the rat central nervous system	44:73	the rat central nervous system	44:73	Developmental expression of Neuregulin-3 in the rat central nervous system.
30328115	7	53	theme	Nrg3	963:966	arg1	mRNA					968:971	Nrg3 mRNA	963:971	Nrg3 mRNA	963:971	Nrg3 mRNA and protein were widely expressed during both embryonic and postnatal ages.
30328115	13	54	from	members	1701:1707	arg1	distinct					1666:1673	distinct	1666:1673	distinct	1666:1673	These findings suggest that Nrg3 plays roles that are distinct from the other Nrg family members.
30328115	2	55	theme	nervous	228:234	arg1	Nrg1-3					244:249	Nrg1-3	244:249	Nrg1-3	244:249	There are three Nrgs expressed in the nervous system (Nrg1-3) and of these Nrg1 has been the best characterized.
30328115	2	55	theme	nervous	228:234	arg1	system					236:241	the nervous system	224:241	the nervous system (Nrg1-3)	224:250	There are three Nrgs expressed in the nervous system (Nrg1-3) and of these Nrg1 has been the best characterized.
30328115	8	56	from	roles	1142:1146	arg1	cell					1151:1154	cell proliferation or migration	1151:1181	cell	1151:1154	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	8	56	from	roles	1142:1146	arg1	migration					1173:1181	migration	1173:1181	migration	1173:1181	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	10	57	from	detection	1328:1336	arg1	striatum					1345:1352	the striatum	1341:1352	the striatum	1341:1352	Multiple thalamic nuclei expressed Nrg3, while detection in the striatum was limited.
30328115	6	58	theme	parvalbumin-expressing	883:904	arg1	neurons					917:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	excitatory, GABAergic and parvalbumin-expressing inhibitory neurons	857:923	Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited.
30328115	10	59	theme	thalamic	1290:1297	arg1	nuclei					1299:1304	Multiple thalamic nuclei	1281:1304	Multiple thalamic nuclei	1281:1304	Multiple thalamic nuclei expressed Nrg3, while detection in the striatum was limited.
30328115	8	60	theme	possible	1133:1140	arg1	roles					1142:1146	possible roles	1133:1146	possible roles in cell proliferation or migration	1133:1181	At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration.
30328115	5	61	theme	Neuro2a	682:688	arg1	cells					690:694	transfected Neuro2a cells	670:694	transfected Neuro2a cells	670:694	In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed.
30328115	10	62	theme	Multiple	1281:1288	arg1	nuclei					1299:1304	Multiple thalamic nuclei	1281:1304	Multiple thalamic nuclei	1281:1304	Multiple thalamic nuclei expressed Nrg3, while detection in the striatum was limited.
30328115	3	63	theme	protein	427:433	arg1	levels					435:440	both the RNA and protein levels	410:440	levels	435:440	To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels.
30328115	4	64	theme	protein	530:536	arg1	expression					538:547	Nrg3 protein expression	525:547	Nrg3 protein expression from embryonic stages to adulthood	525:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	0	65	theme	central	52:58	arg1	system					68:73	the rat central nervous system	44:73	the rat central nervous system	44:73	Developmental expression of Neuregulin-3 in the rat central nervous system.
30328115	4	66	contain	carries	607:613	arg1	it					604:605	it	604:605	it	604:605	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	4	66	contain	carries	607:613	arg2	carbohydrates					624:636	O-linked carbohydrates	615:636	O-linked carbohydrates	615:636	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30328115	1	67	theme	family	119:124	arg1	Neuregulin-3					76:87	Neuregulin-3	76:87	Neuregulin-3 (Nrg3)	76:94	Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia.
30328115	1	67	theme	family	119:124	arg1	member					101:106	a member	99:106	a member of the Nrg family of growth factors identified as risk factors for schizophrenia	99:187	Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia.
30328115	4	68	theme	Nrg3	525:528	arg1	expression					538:547	Nrg3 protein expression	525:547	Nrg3 protein expression from embryonic stages to adulthood	525:582	Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates.
30150325	8	0	theme	modification-mediated	1115:1135	arg1	mechanism					1137:1145	a novel post-translational O-GlcNAc modification-mediated mechanism	1079:1145	a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity	1079:1177	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	6	1	theme	histone	897:903	arg1	modification					905:916	ATX1-mediated H3K4me3 histone modification	875:916	ATX1-mediated H3K4me3 histone modification	875:916	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	5	2	theme	FLOWERING	651:659	arg1	FLC					670:672	FLC	670:672	FLC	670:672	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	2	theme	FLOWERING	651:659	arg1	C					667:667	FLOWERING LOCUS C	651:667	FLOWERING LOCUS C (FLC) locus	651:679	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	7	3	theme	SET	1004:1006	arg1	domain					1008:1013	the SET domain	1000:1013	the SET domain	1000:1013	SEC transfers an O-GlcNAc group on Ser947 of ATX1, which resides in the SET domain, thereby activating ATX1.
30150325	8	4	theme	O-GlcNAc	1106:1113	arg1	mechanism					1137:1145	a novel post-translational O-GlcNAc modification-mediated mechanism	1079:1145	a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity	1079:1177	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	6	5	theme	H3K4me3	889:895	arg1	modification					905:916	ATX1-mediated H3K4me3 histone modification	875:916	ATX1-mediated H3K4me3 histone modification	875:916	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	5	6	theme	LOCUS	661:665	arg1	FLC					670:672	FLC	670:672	FLC	670:672	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	6	theme	LOCUS	661:665	arg1	C					667:667	FLOWERING LOCUS C	651:667	FLOWERING LOCUS C (FLC) locus	651:679	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	7	theme	H3	611:612	arg1	lysine					614:619	histone H3 lysine 4	603:621	reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering	595:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	3	8	theme	plant	418:422	arg1	development					424:434	plant development	418:434	plant development	418:434	However, whether protein O-GlcNAcylation is involved in epigenetic processes during plant development is largely unknown.
30150325	6	9	theme	ATX1-mediated	875:887	arg1	modification					905:916	ATX1-mediated H3K4me3 histone modification	875:916	ATX1-mediated H3K4me3 histone modification	875:916	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	5	10	theme	C	667:667	arg1	locus					675:679	FLOWERING LOCUS C (FLC) locus	651:679	FLOWERING LOCUS C (FLC) locus	651:679	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	10	theme	C	667:667	arg1	regulator					711:719	a key negative regulator	696:719	a key negative regulator of flowering	696:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	11	theme	lysine	614:619	arg1	H3K4me3					639:645	H3K4me3	639:645	H3K4me3	639:645	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	11	theme	lysine	614:619	arg1	trimethylation					623:636	reduced histone H3 lysine 4 trimethylation	595:636	reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering	595:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	4	12	from	OGT	518:520	arg1	Arabidopsis					525:535	Arabidopsis	525:535	Arabidopsis	525:535	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	6	13	theme	FLC	921:923	arg1	locus					925:929	FLC locus	921:929	FLC locus	921:929	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	8	14	theme	novel	1081:1085	arg1	mechanism					1137:1145	a novel post-translational O-GlcNAc modification-mediated mechanism	1079:1145	a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity	1079:1177	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	8	15	theme	post-translational	1087:1104	arg1	mechanism					1137:1145	a novel post-translational O-GlcNAc modification-mediated mechanism	1079:1145	a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity	1079:1177	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	7	16	from	group	958:962	arg1	Ser947					967:972	Ser947	967:972	Ser947 of ATX1	967:980	SEC transfers an O-GlcNAc group on Ser947 of ATX1, which resides in the SET domain, thereby activating ATX1.
30150325	5	17	theme	flowering	724:732	arg1	locus					675:679	FLOWERING LOCUS C (FLC) locus	651:679	FLOWERING LOCUS C (FLC) locus	651:679	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	17	theme	flowering	724:732	arg1	regulator					711:719	a key negative regulator	696:719	a key negative regulator of flowering	696:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	8	18	from	function	1197:1204	arg1	processes					1242:1250	epigenetic processes	1231:1250	epigenetic processes in plants	1231:1260	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	8	19	from	processes	1242:1250	arg1	plants					1255:1260	plants	1255:1260	plants	1255:1260	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	8	20	theme	HKMT	1165:1168	arg1	activity					1170:1177	HKMT activity	1165:1177	HKMT activity	1165:1177	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	1	21	theme	O-GlcNAc	206:213	arg1	transferases					215:226	O-GlcNAc transferases	206:226	O-GlcNAc transferases (OGTs)	206:233	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	1	21	theme	O-GlcNAc	206:213	arg1	OGTs					229:232	OGTs	229:232	OGTs	229:232	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	0	22	theme	O-GlcNAc	12:19	arg1	transferase					21:31	Arabidopsis O-GlcNAc transferase	0:31	Arabidopsis O-GlcNAc transferase SEC	0:35	Arabidopsis O-GlcNAc transferase SEC activates histone methyltransferase ATX1 to regulate flowering.
30150325	6	23	theme	O-GlcNAc	842:849	arg1	modification					851:862	O-GlcNAc modification	842:862	O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus	842:929	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	6	24	theme	TRITHORAX1	772:781	arg1	HOMOLOG					761:767	ARABIDOPSIS HOMOLOG	749:767	ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT),	749:832	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	1	25	theme	Post-translational	101:118	arg1	modification					120:131	Post-translational modification	101:131	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc)	101:188	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	0	26	theme	Arabidopsis	0:10	arg1	transferase					21:31	Arabidopsis O-GlcNAc transferase	0:31	Arabidopsis O-GlcNAc transferase SEC	0:35	Arabidopsis O-GlcNAc transferase SEC activates histone methyltransferase ATX1 to regulate flowering.
30150325	5	27	theme	reduced	595:601	arg1	H3K4me3					639:645	H3K4me3	639:645	H3K4me3	639:645	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	27	theme	reduced	595:601	arg1	trimethylation					623:636	reduced histone H3 lysine 4 trimethylation	595:636	reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering	595:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	8	28	theme	epigenetic	1231:1240	arg1	processes					1242:1250	epigenetic processes	1231:1250	epigenetic processes in plants	1231:1260	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	4	29	theme	flowering	556:564	arg1	phenotype					566:574	an early flowering phenotype	547:574	an early flowering phenotype	547:574	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	5	30	theme	histone	603:609	arg1	lysine					614:619	histone H3 lysine 4	603:621	reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering	595:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	0	31	theme	transferase	21:31	arg1	SEC					33:35	Arabidopsis O-GlcNAc transferase SEC	0:35	Arabidopsis O-GlcNAc transferase SEC	0:35	Arabidopsis O-GlcNAc transferase SEC activates histone methyltransferase ATX1 to regulate flowering.
30150325	4	32	theme	SECRET	495:500	arg1	SEC					509:511	SEC	509:511	SEC	509:511	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	4	32	theme	SECRET	495:500	arg1	AGENT					502:506	SECRET AGENT	495:506	SECRET AGENT (SEC)	495:512	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	4	32	theme	SECRET	495:500	arg1	OGT					518:520	an OGT	515:520	an OGT in Arabidopsis	515:535	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	1	33	theme	proteins	136:143	arg1	modification					120:131	Post-translational modification	101:131	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc)	101:188	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	0	34	theme	histone	47:53	arg1	ATX1					73:76	histone methyltransferase ATX1	47:76	histone methyltransferase ATX1	47:76	Arabidopsis O-GlcNAc transferase SEC activates histone methyltransferase ATX1 to regulate flowering.
30150325	5	35	theme	key	698:700	arg1	locus					675:679	FLOWERING LOCUS C (FLC) locus	651:679	FLOWERING LOCUS C (FLC) locus	651:679	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	35	theme	key	698:700	arg1	regulator					711:719	a key negative regulator	696:719	a key negative regulator of flowering	696:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	2	36	theme	proteins	261:268	arg1	modification					245:256	O-GlcNAc modification	236:256	O-GlcNAc modification of proteins	236:268	O-GlcNAc modification of proteins regulates multiple important biological processes in metazoans.
30150325	6	37	theme	ARABIDOPSIS	749:759	arg1	HOMOLOG					761:767	ARABIDOPSIS HOMOLOG	749:767	ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT),	749:832	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	8	38	theme	O-GlcNAc	1209:1216	arg1	signaling					1218:1226	O-GlcNAc signaling	1209:1226	O-GlcNAc signaling	1209:1226	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	5	39	theme	negative	702:709	arg1	locus					675:679	FLOWERING LOCUS C (FLC) locus	651:679	FLOWERING LOCUS C (FLC) locus	651:679	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	39	theme	negative	702:709	arg1	regulator					711:719	a key negative regulator	696:719	a key negative regulator of flowering	696:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	3	40	theme	protein	351:357	arg1	O-GlcNAcylation					359:373	protein O-GlcNAcylation	351:373	protein O-GlcNAcylation	351:373	However, whether protein O-GlcNAcylation is involved in epigenetic processes during plant development is largely unknown.
30150325	4	41	theme	AGENT	502:506	arg1	function					483:490	function	483:490	function of SECRET AGENT (SEC), an OGT in Arabidopsis,	483:536	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	0	42	theme	methyltransferase	55:71	arg1	ATX1					73:76	histone methyltransferase ATX1	47:76	histone methyltransferase ATX1	47:76	Arabidopsis O-GlcNAc transferase SEC activates histone methyltransferase ATX1 to regulate flowering.
30150325	4	43	theme	early	550:554	arg1	phenotype					566:574	an early flowering phenotype	547:574	an early flowering phenotype	547:574	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	2	44	theme	O-GlcNAc	236:243	arg1	modification					245:256	O-GlcNAc modification	236:256	O-GlcNAc modification of proteins	236:268	O-GlcNAc modification of proteins regulates multiple important biological processes in metazoans.
30150325	7	45	theme	ATX1	977:980	arg1	Ser947					967:972	Ser947	967:972	Ser947 of ATX1	967:980	SEC transfers an O-GlcNAc group on Ser947 of ATX1, which resides in the SET domain, thereby activating ATX1.
30150325	1	46	theme	O-linked	148:155	arg1	β-N-acetylglucosamine					157:177	O-linked β-N-acetylglucosamine	148:177	O-linked β-N-acetylglucosamine (O-GlcNAc)	148:188	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	1	46	theme	O-linked	148:155	arg1	O-GlcNAc					180:187	O-GlcNAc	180:187	O-GlcNAc	180:187	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	5	47	theme	locus	675:679	arg1	H3K4me3					639:645	H3K4me3	639:645	H3K4me3	639:645	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	5	47	theme	locus	675:679	arg1	trimethylation					623:636	reduced histone H3 lysine 4 trimethylation	595:636	reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering	595:732	This results from reduced histone H3 lysine 4 trimethylation (H3K4me3) of FLOWERING LOCUS C (FLC) locus, which encodes a key negative regulator of flowering.
30150325	7	48	theme	O-GlcNAc	949:956	arg1	group					958:962	an O-GlcNAc group	946:962	an O-GlcNAc group on Ser947 of ATX1	946:980	SEC transfers an O-GlcNAc group on Ser947 of ATX1, which resides in the SET domain, thereby activating ATX1.
30150325	1	49	link	O-linked	148:155	arg1	β-N-acetylglucosamine					157:177	O-linked β-N-acetylglucosamine	148:177	O-linked β-N-acetylglucosamine (O-GlcNAc)	148:188	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	1	49	link	O-linked	148:155	arg1	O-GlcNAc					180:187	O-GlcNAc	180:187	O-GlcNAc	180:187	Post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is catalyzed by O-GlcNAc transferases (OGTs).
30150325	4	50	theme	function	483:490	arg1	loss					475:478	loss	475:478	loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis,	475:536	Here, we show that loss of function of SECRET AGENT (SEC), an OGT in Arabidopsis, leads to an early flowering phenotype.
30150325	2	51	theme	biological	299:308	arg1	processes					310:318	multiple important biological processes	280:318	multiple important biological processes	280:318	O-GlcNAc modification of proteins regulates multiple important biological processes in metazoans.
30150325	3	52	gly	O-GlcNAcylation	359:373	arg1	processes					401:409	epigenetic processes	390:409	epigenetic processes	390:409	However, whether protein O-GlcNAcylation is involved in epigenetic processes during plant development is largely unknown.
30150325	6	53	theme	histone	793:799	arg1	methyltransferase					808:824	a histone lysine methyltransferase	791:824	a histone lysine methyltransferase (HKMT)	791:831	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	6	53	theme	histone	793:799	arg1	TRITHORAX1					772:781	TRITHORAX1	772:781	TRITHORAX1 (ATX1)	772:788	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	6	53	theme	histone	793:799	arg1	HKMT					827:830	HKMT	827:830	HKMT	827:830	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	2	54	theme	important	289:297	arg1	processes					310:318	multiple important biological processes	280:318	multiple important biological processes	280:318	O-GlcNAc modification of proteins regulates multiple important biological processes in metazoans.
30150325	6	55	theme	lysine	801:806	arg1	methyltransferase					808:824	a histone lysine methyltransferase	791:824	a histone lysine methyltransferase (HKMT)	791:831	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	6	55	theme	lysine	801:806	arg1	TRITHORAX1					772:781	TRITHORAX1	772:781	TRITHORAX1 (ATX1)	772:788	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	6	55	theme	lysine	801:806	arg1	HKMT					827:830	HKMT	827:830	HKMT	827:830	SEC activates ARABIDOPSIS HOMOLOG OF TRITHORAX1 (ATX1), a histone lysine methyltransferase (HKMT), through O-GlcNAc modification to augment ATX1-mediated H3K4me3 histone modification at FLC locus.
30150325	8	56	theme	signaling	1218:1226	arg1	function					1197:1204	the function	1193:1204	the function of O-GlcNAc signaling in epigenetic processes in plants	1193:1260	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
30150325	3	57	theme	epigenetic	390:399	arg1	processes					401:409	epigenetic processes	390:409	epigenetic processes	390:409	However, whether protein O-GlcNAcylation is involved in epigenetic processes during plant development is largely unknown.
30150325	2	58	theme	multiple	280:287	arg1	processes					310:318	multiple important biological processes	280:318	multiple important biological processes	280:318	O-GlcNAc modification of proteins regulates multiple important biological processes in metazoans.
30150325	8	59	theme	activity	1170:1177	arg1	regulation					1151:1160	regulation	1151:1160	regulation of HKMT activity	1151:1177	Taken together, these results uncover a novel post-translational O-GlcNAc modification-mediated mechanism for regulation of HKMT activity and establish the function of O-GlcNAc signaling in epigenetic processes in plants.
29944994	0	0	theme	insulin	78:84	arg1	resistance					86:95	peripheral insulin resistance	67:95	peripheral insulin resistance	67:95	Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance.
29944994	1	1	theme	nucleocytoplasmic	344:360	arg1	proteins					362:369	nucleocytoplasmic proteins	344:369	nucleocytoplasmic proteins	344:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	4	2	from	mice	778:781	arg1	KO					758:759	KO	758:759	KO	758:759	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	4	2	from	mice	778:781	arg1	knockout					748:755	knockout	748:755	knockout	748:755	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	1	3	theme	O-GlcNAc	161:168	arg1	[OGT					182:185	O-GlcNAc transferase [OGT	161:185	O-GlcNAc transferase [OGT	161:185	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	3	theme	O-GlcNAc	161:168	arg1	transferase					148:158	O-linked N-acetylglucosamine transferase	119:158	O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	119:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	0	4	theme	peripheral	67:76	arg1	resistance					86:95	peripheral insulin resistance	67:95	peripheral insulin resistance	67:95	Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance.
29944994	1	5	theme	proteins	362:369	arg1	group					303:307	the hydroxyl group	290:307	the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	290:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	5	theme	proteins	362:369	arg1	proteins					362:369	nucleocytoplasmic proteins	344:369	nucleocytoplasmic proteins	344:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	5	theme	proteins	362:369	arg1	threonine					322:330	threonine	322:330	threonine	322:330	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	5	theme	proteins	362:369	arg1	serine					312:317	serine	312:317	serine	312:317	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	4	6	theme	insulin	846:852	arg1	resistance					854:863	peripheral insulin resistance	835:863	peripheral insulin resistance	835:863	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	2	7	theme	metabolism	518:527	arg1	process					377:383	This process	372:383	This process	372:383	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	7	theme	metabolism	518:527	arg1	modification					423:434	a common protein posttranslational modification	388:434	a common protein posttranslational modification	388:434	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	7	theme	metabolism	518:527	arg1	sensor					500:505	a known intracellular sensor	478:505	a known intracellular sensor of glucose metabolism	478:527	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	1	8	theme	transferase	170:180	arg1	[OGT					182:185	O-GlcNAc transferase [OGT	161:185	O-GlcNAc transferase [OGT	161:185	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	8	theme	transferase	170:180	arg1	transferase					148:158	O-linked N-acetylglucosamine transferase	119:158	O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	119:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	3	9	from	function	657:664	arg1	brain					680:684	the brain	676:684	the brain	676:684	However, little is known about the function of OGT in the brain.
29944994	8	10	theme	insulin	1479:1485	arg1	sensitivity					1487:1497	peripheral insulin sensitivity	1468:1497	peripheral insulin sensitivity	1468:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	5	11	theme	leptin	1009:1014	arg1	neurons					1036:1042	leptin receptor-expressing neurons	1009:1042	leptin receptor-expressing neurons	1009:1042	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	4	12	theme	OGT	765:767	arg1	KO					758:759	KO	758:759	KO	758:759	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	4	12	theme	OGT	765:767	arg1	knockout					748:755	knockout	748:755	knockout	748:755	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	5	13	theme	leptin	948:953	arg1	loss					1001:1004	the loss	997:1004	the loss of leptin receptor-expressing neurons	997:1042	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	5	13	theme	leptin	948:953	arg1	levels					955:960	serum insulin and leptin levels	930:960	serum insulin and leptin levels	930:960	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	7	14	theme	OGT	1223:1225	arg1	KO					1227:1228	neuronal OGT KO	1214:1228	neuronal OGT KO	1214:1228	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
29944994	2	15	theme	important	542:550	arg1	role					552:555	an important role	539:555	an important role	539:555	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	8	16	theme	body	1451:1454	arg1	weight					1456:1461	body weight	1451:1461	body weight	1451:1461	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	4	17	theme	adult	772:776	arg1	mice					778:781	adult mice	772:781	adult mice	772:781	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	8	18	from	role	1391:1394	arg1	regulation					1419:1428	the regulation	1415:1428	the regulation of feeding behavior, body weight, and peripheral insulin sensitivity	1415:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	6	19	theme	neuronal	1070:1077	arg1	KO					1083:1084	The neuronal OGT KO	1066:1084	The neuronal OGT KO	1066:1084	The neuronal OGT KO exacerbated obesity and insulin resistance induced by high-fat diet.
29944994	2	20	theme	known	480:484	arg1	process					377:383	This process	372:383	This process	372:383	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	20	theme	known	480:484	arg1	modification					423:434	a common protein posttranslational modification	388:434	a common protein posttranslational modification	388:434	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	20	theme	known	480:484	arg1	sensor					500:505	a known intracellular sensor	478:505	a known intracellular sensor of glucose metabolism	478:527	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	1	21	dep	serine	312:317	arg1	residues					332:339	residues	332:339	residues	332:339	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	5	22	from	elevation	917:925	arg1	hypothalamus					1052:1063	the hypothalamus	1048:1063	the hypothalamus	1048:1063	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	5	23	theme	cell	975:978	arg1	death					980:984	neuronal cell death	966:984	neuronal cell death	966:984	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	6	24	theme	OGT	1079:1081	arg1	KO					1083:1084	The neuronal OGT KO	1066:1084	The neuronal OGT KO	1066:1084	The neuronal OGT KO exacerbated obesity and insulin resistance induced by high-fat diet.
29944994	2	25	theme	posttranslational	405:421	arg1	process					377:383	This process	372:383	This process	372:383	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	25	theme	posttranslational	405:421	arg1	modification					423:434	a common protein posttranslational modification	388:434	a common protein posttranslational modification	388:434	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	25	theme	posttranslational	405:421	arg1	sensor					500:505	a known intracellular sensor	478:505	a known intracellular sensor of glucose metabolism	478:527	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	0	26	theme	O-GlcNAc	9:16	arg1	transferase					18:28	Neuronal O-GlcNAc transferase	0:28	Neuronal O-GlcNAc transferase	0:28	Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance.
29944994	2	27	theme	glucose	510:516	arg1	metabolism					518:527	glucose metabolism	510:527	glucose metabolism	510:527	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	4	28	theme	peripheral	835:844	arg1	resistance					854:863	peripheral insulin resistance	835:863	peripheral insulin resistance	835:863	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	5	29	theme	serum	930:934	arg1	insulin					936:942	serum insulin	930:942	serum insulin	930:942	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	2	30	theme	protein	397:403	arg1	process					377:383	This process	372:383	This process	372:383	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	30	theme	protein	397:403	arg1	modification					423:434	a common protein posttranslational modification	388:434	a common protein posttranslational modification	388:434	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	30	theme	protein	397:403	arg1	sensor					500:505	a known intracellular sensor	478:505	a known intracellular sensor of glucose metabolism	478:527	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	0	31	theme	Neuronal	0:7	arg1	transferase					18:28	Neuronal O-GlcNAc transferase	0:28	Neuronal O-GlcNAc transferase	0:28	Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance.
29944994	5	32	theme	insulin	936:942	arg1	loss					1001:1004	the loss	997:1004	the loss of leptin receptor-expressing neurons	997:1042	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	5	32	theme	insulin	936:942	arg1	levels					955:960	serum insulin and leptin levels	930:960	serum insulin and leptin levels	930:960	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	8	33	theme	neuronal	1399:1406	arg1	OGT					1408:1410	neuronal OGT	1399:1410	neuronal OGT	1399:1410	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	2	34	theme	common	390:395	arg1	process					377:383	This process	372:383	This process	372:383	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	34	theme	common	390:395	arg1	modification					423:434	a common protein posttranslational modification	388:434	a common protein posttranslational modification	388:434	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	34	theme	common	390:395	arg1	sensor					500:505	a known intracellular sensor	478:505	a known intracellular sensor of glucose metabolism	478:527	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	1	35	theme	hydroxyl	294:301	arg1	group					303:307	the hydroxyl group	290:307	the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	290:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	35	theme	hydroxyl	294:301	arg1	proteins					362:369	nucleocytoplasmic proteins	344:369	nucleocytoplasmic proteins	344:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	35	theme	hydroxyl	294:301	arg1	threonine					322:330	threonine	322:330	threonine	322:330	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	35	theme	hydroxyl	294:301	arg1	serine					312:317	serine	312:317	serine	312:317	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	36	from	uridine-diphosphate-GlcNAc	260:285	arg1	transfer					208:215	the transfer	204:215	the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	204:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	4	37	from	knockout	748:755	arg1	mice					778:781	adult mice	772:781	adult mice	772:781	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	5	38	theme	neurons	1036:1042	arg1	loss					1001:1004	the loss	997:1004	the loss of leptin receptor-expressing neurons	997:1042	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	5	39	theme	neuronal	966:973	arg1	death					980:984	neuronal cell death	966:984	neuronal cell death	966:984	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	3	40	theme	OGT	669:671	arg1	function					657:664	the function	653:664	the function of OGT in the brain	653:684	However, little is known about the function of OGT in the brain.
29944994	1	41	theme	ogt	102:104	arg1	gene					106:109	The ogt gene	98:109	The ogt gene	98:109	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	41	theme	ogt	102:104	arg1	transferase					148:158	O-linked N-acetylglucosamine transferase	119:158	O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	119:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	2	42	theme	protein	444:450	arg1	O-GlcNAcylation					452:466	protein O-GlcNAcylation	444:466	protein O-GlcNAcylation	444:466	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	43	theme	cellular	571:578	arg1	signaling					580:588	cellular signaling	571:588	cellular signaling	571:588	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	7	44	theme	peripheral	1173:1182	arg1	resistance					1192:1201	the peripheral insulin resistance	1169:1201	the peripheral insulin resistance induced by neuronal OGT KO	1169:1228	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
29944994	8	45	theme	important	1381:1389	arg1	role					1391:1394	an important role	1378:1394	an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity	1378:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	7	46	theme	increased	1304:1312	arg1	sensitivity					1322:1332	increased insulin sensitivity	1304:1332	increased insulin sensitivity several months later	1304:1353	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
29944994	1	47	theme	serine	312:317	arg1	group					303:307	the hydroxyl group	290:307	the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	290:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	47	theme	serine	312:317	arg1	proteins					362:369	nucleocytoplasmic proteins	344:369	nucleocytoplasmic proteins	344:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	47	theme	serine	312:317	arg1	threonine					322:330	threonine	322:330	threonine	322:330	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	47	theme	serine	312:317	arg1	serine					312:317	serine	312:317	serine	312:317	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	8	48	theme	behavior	1441:1448	arg1	regulation					1419:1428	the regulation	1415:1428	the regulation of feeding behavior, body weight, and peripheral insulin sensitivity	1415:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	2	49	theme	intracellular	486:498	arg1	process					377:383	This process	372:383	This process	372:383	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	49	theme	intracellular	486:498	arg1	modification					423:434	a common protein posttranslational modification	388:434	a common protein posttranslational modification	388:434	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	2	49	theme	intracellular	486:498	arg1	sensor					500:505	a known intracellular sensor	478:505	a known intracellular sensor of glucose metabolism	478:527	This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism.
29944994	1	50	link	O-linked	119:126	arg1	[OGT					182:185	O-GlcNAc transferase [OGT	161:185	O-GlcNAc transferase [OGT	161:185	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	50	link	O-linked	119:126	arg1	gene					106:109	The ogt gene	98:109	The ogt gene	98:109	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	50	link	O-linked	119:126	arg1	transferase					148:158	O-linked N-acetylglucosamine transferase	119:158	O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	119:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	8	51	theme	feeding	1433:1439	arg1	behavior					1441:1448	feeding behavior	1433:1448	feeding behavior	1433:1448	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	4	52	theme	weight	818:823	arg1	gain					825:828	body weight gain	813:828	body weight gain	813:828	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	0	53	theme	body	50:53	arg1	weight					55:60	body weight	50:60	body weight	50:60	Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance.
29944994	1	54	theme	threonine	322:330	arg1	group					303:307	the hydroxyl group	290:307	the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	290:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	54	theme	threonine	322:330	arg1	proteins					362:369	nucleocytoplasmic proteins	344:369	nucleocytoplasmic proteins	344:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	54	theme	threonine	322:330	arg1	threonine					322:330	threonine	322:330	threonine	322:330	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	54	theme	threonine	322:330	arg1	serine					312:317	serine	312:317	serine	312:317	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	8	55	theme	peripheral	1468:1477	arg1	sensitivity					1487:1497	peripheral insulin sensitivity	1468:1497	peripheral insulin sensitivity	1468:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	5	56	theme	receptor-expressing	1016:1034	arg1	neurons					1036:1042	leptin receptor-expressing neurons	1009:1042	leptin receptor-expressing neurons	1009:1042	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	4	57	theme	body	813:816	arg1	gain					825:828	body weight gain	813:828	body weight gain	813:828	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	5	58	theme	marked	910:915	arg1	elevation					917:925	marked elevation	910:925	marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus	910:1063	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	8	59	theme	OGT	1408:1410	arg1	role					1391:1394	an important role	1378:1394	an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity	1378:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	5	60	theme	death	980:984	arg1	elevation					917:925	marked elevation	910:925	marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus	910:1063	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	1	61	theme	O-linked	119:126	arg1	[OGT					182:185	O-GlcNAc transferase [OGT	161:185	O-GlcNAc transferase [OGT	161:185	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	61	theme	O-linked	119:126	arg1	gene					106:109	The ogt gene	98:109	The ogt gene	98:109	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	61	theme	O-linked	119:126	arg1	transferase					148:158	O-linked N-acetylglucosamine transferase	119:158	O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	119:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	6	62	theme	high-fat	1140:1147	arg1	diet					1149:1152	high-fat diet	1140:1152	high-fat diet	1140:1152	The neuronal OGT KO exacerbated obesity and insulin resistance induced by high-fat diet.
29944994	1	63	theme	β-N-acetylglucosamine	220:240	arg1	transfer					208:215	the transfer	204:215	the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	204:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	7	64	theme	neuronal	1214:1221	arg1	KO					1227:1228	neuronal OGT KO	1214:1228	neuronal OGT KO	1214:1228	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
29944994	5	65	theme	levels	955:960	arg1	elevation					917:925	marked elevation	910:925	marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus	910:1063	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	1	66	theme	N-acetylglucosamine	128:146	arg1	[OGT					182:185	O-GlcNAc transferase [OGT	161:185	O-GlcNAc transferase [OGT	161:185	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	66	theme	N-acetylglucosamine	128:146	arg1	gene					106:109	The ogt gene	98:109	The ogt gene	98:109	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	1	66	theme	N-acetylglucosamine	128:146	arg1	transferase					148:158	O-linked N-acetylglucosamine transferase	119:158	O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins	119:369	The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins.
29944994	6	67	theme	insulin	1110:1116	arg1	resistance					1118:1127	insulin resistance	1110:1127	insulin resistance	1110:1127	The neuronal OGT KO exacerbated obesity and insulin resistance induced by high-fat diet.
29944994	8	68	theme	sensitivity	1487:1497	arg1	regulation					1419:1428	the regulation	1415:1428	the regulation of feeding behavior, body weight, and peripheral insulin sensitivity	1415:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	8	69	theme	weight	1456:1461	arg1	regulation					1419:1428	the regulation	1415:1428	the regulation of feeding behavior, body weight, and peripheral insulin sensitivity	1415:1497	These findings reveal an important role of neuronal OGT in the regulation of feeding behavior, body weight, and peripheral insulin sensitivity.
29944994	4	70	theme	short-term	790:799	arg1	overeating					801:810	short-term overeating	790:810	short-term overeating	790:810	Here, we report that the CaMKIIα promoter-dependent neuronal knockout (KO) of OGT in adult mice led to short-term overeating, body weight gain, and peripheral insulin resistance.
29944994	5	71	theme	phenotype	872:880	arg1	changes					882:888	These phenotype changes	866:888	These phenotype changes	866:888	These phenotype changes were accompanied by marked elevation of serum insulin and leptin levels and neuronal cell death, including the loss of leptin receptor-expressing neurons, in the hypothalamus.
29944994	7	72	theme	insulin	1314:1320	arg1	sensitivity					1322:1332	increased insulin sensitivity	1304:1332	increased insulin sensitivity several months later	1304:1353	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
29944994	7	73	theme	insulin	1184:1190	arg1	resistance					1192:1201	the peripheral insulin resistance	1169:1201	the peripheral insulin resistance induced by neuronal OGT KO	1169:1228	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
29944994	7	74	theme	several	1334:1340	arg1	months					1342:1347	several months	1334:1347	several months	1334:1347	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
29944994	7	75	theme	own	1250:1252	arg1	2-3 months					1254:1263	its own 2-3 months	1246:1263	its own 2-3 months after OGT KO	1246:1276	Surprisingly, the peripheral insulin resistance induced by neuronal OGT KO was reversed at its own 2-3 months after OGT KO, and the mice even showed increased insulin sensitivity several months later.
31771208	6	0	theme	amino	1019:1023	arg1	changes					1030:1036	The cumulative amino acid changes	1004:1036	The cumulative amino acid changes in the TRI1p sequences	1004:1059	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	6	1	theme	TRI1p	1045:1049	arg1	sequences					1051:1059	the TRI1p sequences	1041:1059	the TRI1p sequences	1041:1059	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	5	2	theme	gene	901:904	arg1	sequences					906:914	TRI1 gene sequences	896:914	TRI1 gene sequences	896:914	There was evidence of selection bias, where TRI1 gene sequences were found to be under positive selection and, therefore, under functional constraints.
31771208	4	3	theme	N-linked	766:773	arg1	glycosylation					775:787	N-linked glycosylation	766:787	N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers	766:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	4	4	gly	glycosylation	775:787	arg1	characteristic					818:831	this TRI1-encoded protein characteristic	792:831	this TRI1-encoded protein characteristic of NX-2 producers	792:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	3	5	theme	non-NX-2	499:506	arg1	producers					508:516	four F. graminearum non-NX-2 producers	479:516	four F. graminearum non-NX-2 producers	479:516	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	7	6	theme	acid	1295:1298	arg1	features					1309:1316	the amino acid sequence features	1285:1316	the amino acid sequence features responsible for the functional diversification of this TRI1p	1285:1377	Together, our findings provide insight into the amino acid sequence features responsible for the functional diversification of this TRI1p.
31771208	3	7	dep	F.	445:446	arg1	graminearum					448:458	F. graminearum	445:458	five F. graminearum NX-2 producers	440:473	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	6	8	from	changes	1030:1036	arg1	sequences					1051:1059	the TRI1p sequences	1041:1059	the TRI1p sequences	1041:1059	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	4	9	theme	producers	841:849	arg1	characteristic					818:831	this TRI1-encoded protein characteristic	792:831	this TRI1-encoded protein characteristic of NX-2 producers	792:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	1	10	theme	Trichothecene	51:63	arg1	mycotoxins					65:74	Trichothecene mycotoxins	51:74	Trichothecene mycotoxins	51:74	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	1	10	theme	Trichothecene	51:63	arg1	class					82:86	a class	80:86	a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species	80:201	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	3	11	theme	functional	548:557	arg1	difference					559:568	the functional difference	544:568	the functional difference of TRI1p of FGNX-2	544:587	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	6	12	theme	FGNX-2	1178:1183	arg1	separation					1164:1173	a distinct separation	1153:1173	a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support	1153:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	6	13	theme	high	1217:1220	arg1	support					1232:1238	high bootstrap support	1217:1238	high bootstrap support	1217:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	5	14	theme	functional	980:989	arg1	constraints					991:1001	functional constraints	980:1001	functional constraints	980:1001	There was evidence of selection bias, where TRI1 gene sequences were found to be under positive selection and, therefore, under functional constraints.
31771208	4	15	theme	N-X-S/T	720:726	arg1	sequons					728:734	post-translational N-X-S/T sequons	701:734	the post-translational N-X-S/T sequons motif	697:740	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	2	16	from	variation	215:223	arg1	gene					237:240	the TRI1 gene	228:240	the TRI1 gene	228:240	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	7	17	theme	sequence	1300:1307	arg1	features					1309:1316	the amino acid sequence features	1285:1316	the amino acid sequence features responsible for the functional diversification of this TRI1p	1285:1377	Together, our findings provide insight into the amino acid sequence features responsible for the functional diversification of this TRI1p.
31771208	4	18	theme	signature	615:623	arg1	motifs					625:630	several signature motifs	607:630	several signature motifs of fungal P450s	607:646	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	4	19	theme	glycosylation	775:787	arg1	motif					736:740	the post-translational N-X-S/T sequons motif	697:740	the post-translational N-X-S/T sequons motif	697:740	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	4	19	theme	glycosylation	775:787	arg1	indicative					752:761	indicative	752:761	indicative	752:761	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	3	20	theme	Fusarium	412:419	arg1	producers					465:473	five F. graminearum NX-2 producers	440:473	five F. graminearum NX-2 producers	440:473	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	3	20	theme	Fusarium	412:419	arg1	producers					508:516	four F. graminearum non-NX-2 producers	479:516	four F. graminearum non-NX-2 producers	479:516	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	3	20	theme	Fusarium	412:419	arg1	species					421:427	Fusarium species	412:427	Fusarium species	412:427	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	1	21	theme	certain	161:167	arg1	species					195:201	certain plant pathogenic Fusarium species	161:201	certain plant pathogenic Fusarium species	161:201	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	3	22	theme	TRI1	394:397	arg1	sequences					399:407	52 translated TRI1 sequences	380:407	52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers,	380:517	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	7	23	theme	functional	1338:1347	arg1	diversification					1349:1363	the functional diversification	1334:1363	the functional diversification of this TRI1p	1334:1377	Together, our findings provide insight into the amino acid sequence features responsible for the functional diversification of this TRI1p.
31771208	2	24	theme	A	264:264	arg1	trichothecene					266:278	a novel Type A trichothecene	251:278	a novel Type A trichothecene called NX-2 in strains of F. graminearum	251:319	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	6	25	theme	phylogenetic	1083:1094	arg1	analyses					1096:1103	the phylogenetic analyses	1079:1103	the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support	1079:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	1	26	theme	plant	169:173	arg1	species					195:201	certain plant pathogenic Fusarium species	161:201	certain plant pathogenic Fusarium species	161:201	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	0	27	theme	Sequence	12:19	arg1	Analysis					21:28	Comparative Sequence Analysis	0:28	Comparative Sequence Analysis of TRI1 of Fusarium	0:48	Comparative Sequence Analysis of TRI1 of Fusarium.
31771208	6	28	with	producers	1202:1210	arg1	support					1232:1238	high bootstrap support	1217:1238	high bootstrap support	1217:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	2	29	theme	F.	306:307	arg1	graminearum					309:319	F. graminearum	306:319	F. graminearum	306:319	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	6	30	from	producers	1202:1210	arg1	separation					1164:1173	a distinct separation	1153:1173	a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support	1153:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	1	31	theme	pathogenic	175:184	arg1	species					195:201	certain plant pathogenic Fusarium species	161:201	certain plant pathogenic Fusarium species	161:201	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	0	32	theme	Comparative	0:10	arg1	Analysis					21:28	Comparative Sequence Analysis	0:28	Comparative Sequence Analysis of TRI1 of Fusarium	0:48	Comparative Sequence Analysis of TRI1 of Fusarium.
31771208	5	33	theme	selection	874:882	arg1	bias					884:887	selection bias	874:887	selection bias	874:887	There was evidence of selection bias, where TRI1 gene sequences were found to be under positive selection and, therefore, under functional constraints.
31771208	1	34	theme	Fusarium	186:193	arg1	species					195:201	certain plant pathogenic Fusarium species	161:201	certain plant pathogenic Fusarium species	161:201	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	3	35	theme	systematic	357:366	arg1	analysis					368:375	a systematic analysis	355:375	a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers,	355:517	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	6	36	theme	bootstrap	1222:1230	arg1	support					1232:1238	high bootstrap support	1217:1238	high bootstrap support	1217:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	1	37	theme	secondary	91:99	arg1	species					195:201	certain plant pathogenic Fusarium species	161:201	certain plant pathogenic Fusarium species	161:201	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	1	37	theme	secondary	91:99	arg1	metabolites					101:111	secondary metabolites	91:111	secondary metabolites	91:111	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	4	38	theme	motifs	625:630	arg1	assessment					593:602	An assessment	590:602	An assessment of several signature motifs of fungal P450s	590:646	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	5	39	theme	positive	939:946	arg1	selection					948:956	positive selection	939:956	positive selection	939:956	There was evidence of selection bias, where TRI1 gene sequences were found to be under positive selection and, therefore, under functional constraints.
31771208	6	40	theme	FG-non-NX-2	1190:1200	arg1	producers					1202:1210	FG-non-NX-2 producers	1190:1210	FG-non-NX-2 producers with high bootstrap support	1190:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	3	41	theme	bioinformatics	330:343	arg1	approach					345:352	a bioinformatics approach	328:352	a bioinformatics approach	328:352	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	1	42	theme	metabolites	101:111	arg1	mycotoxins					65:74	Trichothecene mycotoxins	51:74	Trichothecene mycotoxins	51:74	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	1	42	theme	metabolites	101:111	arg1	class					82:86	a class	80:86	a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species	80:201	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	3	43	theme	NX-2	460:463	arg1	producers					465:473	five F. graminearum NX-2 producers	440:473	five F. graminearum NX-2 producers	440:473	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	3	44	theme	sequences	399:407	arg1	analysis					368:375	a systematic analysis	355:375	a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers,	355:517	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	4	45	link	N-linked	766:773	arg1	glycosylation					775:787	N-linked glycosylation	766:787	N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers	766:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	7	46	theme	responsible	1318:1328	arg1	features					1309:1316	the amino acid sequence features	1285:1316	the amino acid sequence features responsible for the functional diversification of this TRI1p	1285:1377	Together, our findings provide insight into the amino acid sequence features responsible for the functional diversification of this TRI1p.
31771208	3	47	theme	FGNX-2	582:587	arg1	TRI1p					573:577	TRI1p	573:577	TRI1p of FGNX-2	573:587	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	3	48	theme	species	421:427	arg1	sequences					399:407	52 translated TRI1 sequences	380:407	52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers,	380:517	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	4	49	theme	fungal	635:640	arg1	P450s					642:646	fungal P450s	635:646	fungal P450s	635:646	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	0	50	theme	TRI1	33:36	arg1	Analysis					21:28	Comparative Sequence Analysis	0:28	Comparative Sequence Analysis of TRI1 of Fusarium	0:48	Comparative Sequence Analysis of TRI1 of Fusarium.
31771208	5	51	theme	bias	884:887	arg1	evidence					862:869	evidence	862:869	evidence of selection bias	862:887	There was evidence of selection bias, where TRI1 gene sequences were found to be under positive selection and, therefore, under functional constraints.
31771208	2	52	theme	TRI1	232:235	arg1	gene					237:240	the TRI1 gene	228:240	the TRI1 gene	228:240	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	3	53	theme	F.	445:446	arg1	producers					465:473	five F. graminearum NX-2 producers	440:473	five F. graminearum NX-2 producers	440:473	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	3	54	theme	translated	383:392	arg1	sequences					399:407	52 translated TRI1 sequences	380:407	52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers,	380:517	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	4	55	theme	acid	663:666	arg1	substitutions					668:680	amino acid substitutions	657:680	amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers	657:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	3	56	theme	TRI1p	573:577	arg1	difference					559:568	the functional difference	544:568	the functional difference of TRI1p of FGNX-2	544:587	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	4	57	theme	post-translational	701:718	arg1	sequons					728:734	post-translational N-X-S/T sequons	701:734	the post-translational N-X-S/T sequons motif	697:740	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	0	58	theme	Fusarium	41:48	arg1	TRI1					33:36	TRI1	33:36	TRI1 of Fusarium	33:48	Comparative Sequence Analysis of TRI1 of Fusarium.
31771208	4	59	theme	NX-2	836:839	arg1	producers					841:849	NX-2 producers	836:849	NX-2 producers	836:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	7	60	theme	TRI1p	1373:1377	arg1	diversification					1349:1363	the functional diversification	1334:1363	the functional diversification of this TRI1p	1334:1377	Together, our findings provide insight into the amino acid sequence features responsible for the functional diversification of this TRI1p.
31771208	3	61	theme	F.	484:485	arg1	producers					508:516	four F. graminearum non-NX-2 producers	479:516	four F. graminearum non-NX-2 producers	479:516	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	6	62	theme	acid	1025:1028	arg1	changes					1030:1036	The cumulative amino acid changes	1004:1036	The cumulative amino acid changes in the TRI1p sequences	1004:1059	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	2	63	theme	Functional	204:213	arg1	variation					215:223	Functional variation	204:223	Functional variation in the TRI1 gene	204:240	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	2	64	theme	Type	259:262	arg1	trichothecene					266:278	a novel Type A trichothecene	251:278	a novel Type A trichothecene called NX-2 in strains of F. graminearum	251:319	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	4	65	theme	characteristic	818:831	arg1	glycosylation					775:787	N-linked glycosylation	766:787	N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers	766:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	1	66	theme	multiple	125:132	arg1	genera					134:139	multiple genera	125:139	multiple genera of fungi	125:148	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	6	67	theme	species-specific	1120:1135	arg1	clustering					1137:1146	species-specific clustering	1120:1146	species-specific clustering	1120:1146	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	3	68	dep	F.	484:485	arg1	graminearum					487:497	F. graminearum	484:497	four F. graminearum non-NX-2 producers	479:516	Using a bioinformatics approach, a systematic analysis of 52 translated TRI1 sequences of Fusarium species, including five F. graminearum NX-2 producers and four F. graminearum non-NX-2 producers, was conducted to explain the functional difference of TRI1p of FGNX-2.
31771208	2	69	theme	novel	253:257	arg1	trichothecene					266:278	a novel Type A trichothecene	251:278	a novel Type A trichothecene called NX-2 in strains of F. graminearum	251:319	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	2	70	theme	graminearum	309:319	arg1	strains					295:301	strains	295:301	strains of F. graminearum	295:319	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	2	71	from	NX-2	287:290	arg1	strains					295:301	strains	295:301	strains of F. graminearum	295:319	Functional variation in the TRI1 gene produces a novel Type A trichothecene called NX-2 in strains of F. graminearum.
31771208	4	72	theme	sequons	728:734	arg1	motif					736:740	the post-translational N-X-S/T sequons motif	697:740	the post-translational N-X-S/T sequons motif	697:740	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	4	72	theme	sequons	728:734	arg1	indicative					752:761	indicative	752:761	indicative	752:761	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	4	73	theme	protein	810:816	arg1	characteristic					818:831	this TRI1-encoded protein characteristic	792:831	this TRI1-encoded protein characteristic of NX-2 producers	792:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	5	74	theme	TRI1	896:899	arg1	sequences					906:914	TRI1 gene sequences	896:914	TRI1 gene sequences	896:914	There was evidence of selection bias, where TRI1 gene sequences were found to be under positive selection and, therefore, under functional constraints.
31771208	4	75	theme	P450s	642:646	arg1	motifs					625:630	several signature motifs	607:630	several signature motifs of fungal P450s	607:646	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	4	76	theme	several	607:613	arg1	motifs					625:630	several signature motifs	607:630	several signature motifs of fungal P450s	607:646	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	4	77	theme	amino	657:661	arg1	substitutions					668:680	amino acid substitutions	657:680	amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers	657:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	6	78	theme	distinct	1155:1162	arg1	separation					1164:1173	a distinct separation	1153:1173	a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support	1153:1238	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31771208	4	79	theme	TRI1-encoded	797:808	arg1	characteristic					818:831	this TRI1-encoded protein characteristic	792:831	this TRI1-encoded protein characteristic of NX-2 producers	792:849	An assessment of several signature motifs of fungal P450s revealed amino acid substitutions in addition to the post-translational N-X-S/T sequons motif, which is indicative of N-linked glycosylation of this TRI1-encoded protein characteristic of NX-2 producers.
31771208	7	80	theme	amino	1289:1293	arg1	features					1309:1316	the amino acid sequence features	1285:1316	the amino acid sequence features responsible for the functional diversification of this TRI1p	1285:1377	Together, our findings provide insight into the amino acid sequence features responsible for the functional diversification of this TRI1p.
31771208	1	81	theme	fungi	144:148	arg1	genera					134:139	multiple genera	125:139	multiple genera of fungi	125:148	Trichothecene mycotoxins are a class of secondary metabolites produced by multiple genera of fungi, including certain plant pathogenic Fusarium species.
31771208	6	82	theme	cumulative	1008:1017	arg1	changes					1030:1036	The cumulative amino acid changes	1004:1036	The cumulative amino acid changes in the TRI1p sequences	1004:1059	The cumulative amino acid changes in the TRI1p sequences were reflected in the phylogenetic analyses which revealed species-specific clustering with a distinct separation of FGNX-2 from FG-non-NX-2 producers with high bootstrap support.
31589168	1	0	theme	viral	320:324	arg1	discontinuation					344:358	plasma viral rebound following discontinuation	313:358	plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans	313:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	3	1	theme	HIV-infected	676:687	arg1	individuals					705:715	HIV-infected and -uninfected individuals	676:715	HIV-infected and -uninfected individuals	676:715	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	5	2	theme	cells	977:981	arg1	incubation					941:950	a short-term incubation	928:950	a short-term incubation of PGT151 and primary NK cells	928:981	In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death.
31589168	1	3	from	humans	416:421	arg1	discontinuation					344:358	plasma viral rebound following discontinuation	313:358	plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans	313:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	4	theme	rebound	326:332	arg1	discontinuation					344:358	plasma viral rebound following discontinuation	313:358	plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans	313:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	4	5	theme	CD8+	796:799	arg1	cells					803:807	activated CD4+ and CD8+ T cells	777:807	activated CD4+ and CD8+ T cells	777:807	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	6	6	from	outcomes	1146:1153	arg1	studies					1175:1181	passive-transfer studies	1158:1181	passive-transfer studies	1158:1181	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	4	7	theme	T	801:801	arg1	cells					803:807	activated CD4+ and CD8+ T cells	777:807	activated CD4+ and CD8+ T cells	777:807	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	1	8	from	models	396:401	arg1	discontinuation					344:358	plasma viral rebound following discontinuation	313:358	plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans	313:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	9	theme	following	334:342	arg1	discontinuation					344:358	plasma viral rebound following discontinuation	313:358	plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans	313:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	6	10	theme	screening	1225:1233	arg1	importance					1202:1211	the importance	1198:1211	the importance of antibody screening against primary lymphocytes	1198:1261	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	6	11	theme	uninfected/bystander	1086:1105	arg1	cells					1107:1111	uninfected/bystander cells	1086:1111	uninfected/bystander cells	1086:1111	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	6	12	theme	certain	1064:1070	arg1	bNAbs					1072:1076	certain bNAbs	1064:1076	certain bNAbs	1064:1076	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	4	13	theme	enzymatic	867:875	arg1	inhibition					877:886	enzymatic inhibition	867:886	enzymatic inhibition of N-linked glycosylation	867:912	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	6	14	theme	antibody	1216:1223	arg1	screening					1225:1233	antibody screening	1216:1233	antibody screening	1216:1233	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	4	15	theme	N-linked	891:898	arg1	glycosylation					900:912	N-linked glycosylation	891:912	N-linked glycosylation	891:912	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	4	16	theme	activated	777:785	arg1	cells					803:807	activated CD4+ and CD8+ T cells	777:807	activated CD4+ and CD8+ T cells	777:807	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	1	17	theme	antiretroviral	363:376	arg1	therapy					378:384	antiretroviral therapy	363:384	antiretroviral therapy in animal models and infected humans	363:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	18	from	therapy	378:384	arg1	models					396:401	animal models	389:401	animal models	389:401	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	18	from	therapy	378:384	arg1	humans					416:421	infected humans	407:421	infected humans	407:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	19	theme	human	177:181	arg1	HIV					207:209	HIV	207:209	HIV	207:209	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	19	theme	human	177:181	arg1	virus					200:204	the human immunodeficiency virus	173:204	the human immunodeficiency virus (HIV)	173:210	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	0	20	theme	HIV-specific	17:28	arg1	antibodies					43:52	Glycan-dependent HIV-specific neutralizing antibodies	0:52	Glycan-dependent HIV-specific neutralizing antibodies	0:52	Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals.
31589168	1	21	theme	therapy	378:384	arg1	discontinuation					344:358	plasma viral rebound following discontinuation	313:358	plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans	313:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	2	22	theme	primary	489:495	arg1	lymphocytes					497:507	primary lymphocytes	489:507	primary lymphocytes	489:507	However, the degree and extent to which such bNAbs interact with primary lymphocytes have not been fully delineated.
31589168	1	23	theme	immunodeficiency	183:198	arg1	HIV					207:209	HIV	207:209	HIV	207:209	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	23	theme	immunodeficiency	183:198	arg1	virus					200:204	the human immunodeficiency virus	173:204	the human immunodeficiency virus (HIV)	173:210	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	0	24	theme	Glycan-dependent	0:15	arg1	antibodies					43:52	Glycan-dependent HIV-specific neutralizing antibodies	0:52	Glycan-dependent HIV-specific neutralizing antibodies	0:52	Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals.
31589168	1	25	theme	virus	268:272	arg1	transmission					248:259	transmission	248:259	transmission of the virus	248:272	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	2	26	dep	degree	437:442	arg1	the					433:435	the	433:435	the	433:435	However, the degree and extent to which such bNAbs interact with primary lymphocytes have not been fully delineated.
31589168	3	27	theme	activated	630:638	arg1	T					640:640	activated T	630:640	activated T	630:640	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	1	28	from	discontinuation	344:358	arg1	models					396:401	animal models	389:401	animal models	389:401	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	28	from	discontinuation	344:358	arg1	humans					416:421	infected humans	407:421	infected humans	407:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	3	29	theme	-uninfected	693:703	arg1	individuals					705:715	HIV-infected and -uninfected individuals	676:715	HIV-infected and -uninfected individuals	676:715	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	5	30	theme	primary	966:972	arg1	cells					977:981	primary NK cells	966:981	primary NK cells	966:981	In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death.
31589168	5	31	theme	NK	974:975	arg1	cells					977:981	primary NK cells	966:981	primary NK cells	966:981	In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death.
31589168	0	32	theme	neutralizing	30:41	arg1	antibodies					43:52	Glycan-dependent HIV-specific neutralizing antibodies	0:52	Glycan-dependent HIV-specific neutralizing antibodies	0:52	Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals.
31589168	1	33	theme	potent	114:119	arg1	bNAbs					158:162	bNAbs	158:162	bNAbs	158:162	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	33	theme	potent	114:119	arg1	antibodies					146:155	highly potent and broadly neutralizing antibodies	107:155	highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV)	107:210	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	2	34	theme	such	464:467	arg1	bNAbs					469:473	such bNAbs	464:473	such bNAbs	464:473	However, the degree and extent to which such bNAbs interact with primary lymphocytes have not been fully delineated.
31589168	1	35	theme	viral	284:288	arg1	replication					290:300	viral replication	284:300	viral replication	284:300	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	6	36	theme	passive-transfer	1158:1173	arg1	studies					1175:1181	passive-transfer studies	1158:1181	passive-transfer studies	1158:1181	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	1	37	theme	animal	389:394	arg1	models					396:401	animal models	389:401	animal models	389:401	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	6	38	theme	primary	1243:1249	arg1	lymphocytes					1251:1261	primary lymphocytes	1243:1261	primary lymphocytes	1243:1261	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	5	39	theme	cellular	1008:1015	arg1	death					1017:1021	cellular death	1008:1021	cellular death	1008:1021	In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death.
31589168	5	40	theme	PGT151	955:960	arg1	incubation					941:950	a short-term incubation	928:950	a short-term incubation of PGT151 and primary NK cells	928:981	In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death.
31589168	4	41	link	N-linked	891:898	arg1	glycosylation					900:912	N-linked glycosylation	891:912	N-linked glycosylation	891:912	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	4	42	theme	glycosylation	900:912	arg1	inhibition					877:886	enzymatic inhibition	867:886	enzymatic inhibition of N-linked glycosylation	867:912	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	3	43	theme	certain	560:566	arg1	bNAbs					585:589	certain glycan-dependent bNAbs	560:589	certain glycan-dependent bNAbs	560:589	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	3	43	theme	certain	560:566	arg1	PGT151					611:616	PGT151	611:616	PGT151	611:616	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	3	43	theme	certain	560:566	arg1	PGT121					600:605	PGT121	600:605	PGT121	600:605	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	4	44	theme	CD4+	787:790	arg1	cells					803:807	activated CD4+ and CD8+ T cells	777:807	activated CD4+ and CD8+ T cells	777:807	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	3	45	theme	individuals	705:715	arg1	cells					667:671	B, activated T, and natural killer (NK) cells	627:671	B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals	627:715	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	3	46	theme	natural	647:653	arg1	NK					663:664	NK	663:664	NK	663:664	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	3	46	theme	natural	647:653	arg1	killer					655:660	natural killer	647:660	natural killer (NK)	647:665	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	1	47	theme	infected	407:414	arg1	humans					416:421	infected humans	407:421	infected humans	407:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	3	48	theme	glycan-dependent	568:583	arg1	bNAbs					585:589	certain glycan-dependent bNAbs	560:589	certain glycan-dependent bNAbs	560:589	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	3	48	theme	glycan-dependent	568:583	arg1	PGT151					611:616	PGT151	611:616	PGT151	611:616	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	3	48	theme	glycan-dependent	568:583	arg1	PGT121					600:605	PGT121	600:605	PGT121	600:605	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	3	49	theme	T	640:640	arg1	cells					667:671	B, activated T, and natural killer (NK) cells	627:671	B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals	627:715	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	4	50	theme	bNAbs	735:739	arg1	Binding					718:724	Binding	718:724	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells	718:807	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	1	51	theme	neutralizing	133:144	arg1	bNAbs					158:162	bNAbs	158:162	bNAbs	158:162	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	1	51	theme	neutralizing	133:144	arg1	antibodies					146:155	highly potent and broadly neutralizing antibodies	107:155	highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV)	107:210	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	6	52	theme	bNAbs	1072:1076	arg1	propensity					1050:1059	the propensity	1046:1059	the propensity of certain bNAbs to bind uninfected/bystander cells	1046:1111	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	4	53	theme	complex-type	825:836	arg1	glycans					838:844	complex-type glycans	825:844	complex-type glycans	825:844	Binding of these bNAbs, particularly PGT121 and PGT151, to activated CD4+ and CD8+ T cells was mediated by complex-type glycans and was abrogated by enzymatic inhibition of N-linked glycosylation.
31589168	3	54	theme	B	627:627	arg1	cells					667:671	B, activated T, and natural killer (NK) cells	627:671	B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals	627:715	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31589168	6	55	theme	unexpected	1135:1144	arg1	outcomes					1146:1153	unexpected outcomes	1135:1153	unexpected outcomes in passive-transfer studies	1135:1181	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	1	56	theme	antibodies	146:155	arg1	number					97:102	A number	95:102	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV)	95:210	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	0	57	theme	individuals	82:92	arg1	cells					62:66	cells	62:66	cells of uninfected individuals	62:92	Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals.
31589168	5	58	theme	short-term	930:939	arg1	incubation					941:950	a short-term incubation	928:950	a short-term incubation of PGT151 and primary NK cells	928:981	In addition, a short-term incubation of PGT151 and primary NK cells led to degranulation and cellular death.
31589168	6	59	contain	has	1113:1115	arg2	potential					1121:1129	the potential	1117:1129	the potential for unexpected outcomes in passive-transfer studies	1117:1181	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	6	59	contain	has	1113:1115	arg1	propensity					1050:1059	the propensity	1046:1059	the propensity of certain bNAbs to bind uninfected/bystander cells	1046:1111	Our data suggest that the propensity of certain bNAbs to bind uninfected/bystander cells has the potential for unexpected outcomes in passive-transfer studies and underscore the importance of antibody screening against primary lymphocytes.
31589168	0	60	theme	uninfected	71:80	arg1	individuals					82:92	uninfected individuals	71:92	uninfected individuals	71:92	Glycan-dependent HIV-specific neutralizing antibodies bind to cells of uninfected individuals.
31589168	1	61	theme	plasma	313:318	arg1	discontinuation					344:358	plasma viral rebound following discontinuation	313:358	plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans	313:421	A number of highly potent and broadly neutralizing antibodies (bNAbs) against the human immunodeficiency virus (HIV) have recently been shown to prevent transmission of the virus, suppress viral replication, and delay plasma viral rebound following discontinuation of antiretroviral therapy in animal models and infected humans.
31589168	3	62	theme	killer	655:660	arg1	cells					667:671	B, activated T, and natural killer (NK) cells	627:671	B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals	627:715	Here, we show that certain glycan-dependent bNAbs, such as PGT121 and PGT151, bind to B, activated T, and natural killer (NK) cells of HIV-infected and -uninfected individuals.
31281932	4	0	theme	therapeutic	533:543	arg1	proteins					545:552	therapeutic proteins	533:552	therapeutic proteins	533:552	The in vitro modification of therapeutic proteins by recombinant sialyltransferases offers a promising and elegant strategy to overcome this problem.
31281932	5	1	theme	sialyltransferases	708:725	arg1	characterization					688:703	characterization	688:703	characterization	688:703	Thus, the detailed expression and characterization of sialyltransferases for completion of the glycan chains is of great interest to the community.
31281932	5	1	theme	sialyltransferases	708:725	arg1	expression					673:682	detailed expression	664:682	detailed expression	664:682	Thus, the detailed expression and characterization of sialyltransferases for completion of the glycan chains is of great interest to the community.
31281932	8	2	dep	different	1167:1175	arg1	therapeutic					1177:1187	therapeutic	1177:1187	therapeutic	1177:1187	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	4	3	theme	recombinant	557:567	arg1	sialyltransferases					569:586	recombinant sialyltransferases	557:586	recombinant sialyltransferases	557:586	The in vitro modification of therapeutic proteins by recombinant sialyltransferases offers a promising and elegant strategy to overcome this problem.
31281932	8	4	theme	N-linked	1147:1154	arg1	glycans					1156:1162	N-linked glycans	1147:1162	N-linked glycans of different therapeutic proteins	1147:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	3	5	with	proteins	433:440	arg1	acids					475:479	appropriate terminal sialic acids	447:479	appropriate terminal sialic acids	447:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	7	6	theme	glycoprotein	959:970	arg1	substrates					972:981	glycoprotein substrates	959:981	glycoprotein substrates	959:981	sialyltransferase using glycoprotein substrates in a 96-well microtiter-plate-based assay.
31281932	8	7	theme	glycans	1156:1162	arg1	modification					1131:1142	modification	1131:1142	modification of N-linked glycans of different therapeutic proteins	1131:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	8	8	from	H.	1091:1092	arg1	catalyst					1118:1125	an excellent catalyst	1105:1125	an excellent catalyst for modification of N-linked glycans of different therapeutic proteins	1105:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	8	8	from	H.	1091:1092	arg1	α2,6-sialyltransferase					1063:1084	the recombinant α2,6-sialyltransferase	1047:1084	the recombinant α2,6-sialyltransferase from H. cetorum	1047:1100	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	3	9	theme	Expression	358:367	arg1	systems					369:375	Expression systems	358:375	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids	358:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	4	10	theme	in	508:509	arg1	modification					517:528	The in vitro modification	504:528	The in vitro modification of therapeutic proteins by recombinant sialyltransferases	504:586	The in vitro modification of therapeutic proteins by recombinant sialyltransferases offers a promising and elegant strategy to overcome this problem.
31281932	5	11	theme	detailed	664:671	arg1	expression					673:682	detailed expression	664:682	detailed expression	664:682	Thus, the detailed expression and characterization of sialyltransferases for completion of the glycan chains is of great interest to the community.
31281932	3	12	theme	sialic	468:473	arg1	acids					475:479	appropriate terminal sialic acids	447:479	appropriate terminal sialic acids	447:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	1	13	theme	fastest	172:178	arg1	areas					188:192	the fastest growing areas	168:192	the fastest growing areas of biotechnology	168:209	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	3	14	gly	glycosylated	408:419	arg1	proteins					433:440	fully glycosylated therapeutic proteins	402:440	fully glycosylated therapeutic proteins with appropriate terminal sialic acids	402:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	1	15	theme	growing	180:186	arg1	areas					188:192	the fastest growing areas	168:192	the fastest growing areas of biotechnology	168:209	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	3	16	theme	glycosylated	408:419	arg1	proteins					433:440	fully glycosylated therapeutic proteins	402:440	fully glycosylated therapeutic proteins with appropriate terminal sialic acids	402:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	8	17	theme	excellent	1108:1116	arg1	catalyst					1118:1125	an excellent catalyst	1105:1125	an excellent catalyst for modification of N-linked glycans of different therapeutic proteins	1105:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	8	17	theme	excellent	1108:1116	arg1	α2,6-sialyltransferase					1063:1084	the recombinant α2,6-sialyltransferase	1047:1084	the recombinant α2,6-sialyltransferase from H. cetorum	1047:1100	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	1	18	theme	therapeutic	98:108	arg1	proteins					110:117	therapeutic proteins	98:117	therapeutic proteins for the treatment of numerous diseases	98:156	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	5	19	theme	glycan	749:754	arg1	chains					756:761	the glycan chains	745:761	the glycan chains	745:761	Thus, the detailed expression and characterization of sialyltransferases for completion of the glycan chains is of great interest to the community.
31281932	1	20	theme	areas	188:192	arg1	areas					188:192	the fastest growing areas	168:192	the fastest growing areas of biotechnology	168:209	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	1	20	theme	areas	188:192	arg1	one					161:163	one	161:163	one	161:163	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	1	20	theme	areas	188:192	arg1	development					83:93	The development	79:93	The development of therapeutic proteins for the treatment of numerous diseases	79:156	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	3	21	theme	therapeutic	421:431	arg1	proteins					433:440	fully glycosylated therapeutic proteins	402:440	fully glycosylated therapeutic proteins with appropriate terminal sialic acids	402:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	4	22	theme	elegant	611:617	arg1	strategy					619:626	a promising and elegant strategy	595:626	a promising and elegant strategy to overcome this problem	595:651	The in vitro modification of therapeutic proteins by recombinant sialyltransferases offers a promising and elegant strategy to overcome this problem.
31281932	8	23	theme	proteins	1189:1196	arg1	glycans					1156:1162	N-linked glycans	1147:1162	N-linked glycans of different therapeutic proteins	1147:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	6	24	theme	Helicobacter	852:863	arg1	cetorum					865:871	Helicobacter cetorum	852:871	Helicobacter cetorum	852:871	We identified a novel α2,6-sialyltransferase from Helicobacter cetorum and compared it to the human ST6Gal1 and a Photobacterium sp.
31281932	2	25	theme	glycosylation	322:334	arg1	state					336:340	the glycosylation state	318:340	the glycosylation state of the protein	318:355	Therapeutic efficacy and serum half-life are particularly important, and these properties rely heavily on the glycosylation state of the protein.
31281932	1	26	theme	biotechnology	197:209	arg1	areas					188:192	the fastest growing areas	168:192	the fastest growing areas of biotechnology	168:209	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	1	27	theme	proteins	110:117	arg1	development					83:93	The development	79:93	The development of therapeutic proteins for the treatment of numerous diseases	79:156	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	1	27	theme	proteins	110:117	arg1	one					161:163	one	161:163	one	161:163	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	1	27	theme	proteins	110:117	arg1	areas					188:192	the fastest growing areas	168:192	the fastest growing areas of biotechnology	168:209	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	5	28	theme	great	769:773	arg1	interest					775:782	great interest	769:782	great interest	769:782	Thus, the detailed expression and characterization of sialyltransferases for completion of the glycan chains is of great interest to the community.
31281932	3	29	theme	appropriate	447:457	arg1	acids					475:479	appropriate terminal sialic acids	447:479	appropriate terminal sialic acids	447:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	4	30	dep	in	508:509	arg1	vitro					511:515	vitro	511:515	vitro	511:515	The in vitro modification of therapeutic proteins by recombinant sialyltransferases offers a promising and elegant strategy to overcome this problem.
31281932	8	31	dep	H.	1091:1092	arg1	cetorum					1094:1100	H. cetorum	1091:1100	H. cetorum	1091:1100	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	3	32	theme	terminal	459:466	arg1	acids					475:479	appropriate terminal sialic acids	447:479	appropriate terminal sialic acids	447:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	7	33	gly	glycoprotein	959:970	arg1	glycoprotein					959:970	glycoprotein substrates	959:981	glycoprotein substrates	959:981	sialyltransferase using glycoprotein substrates in a 96-well microtiter-plate-based assay.
31281932	0	34	theme	proteins	69:76	arg1	sialylation					42:52	sialylation	42:52	sialylation of therapeutic proteins	42:76	Comparison of α2,6-sialyltransferases for sialylation of therapeutic proteins.
31281932	6	35	theme	Photobacterium	916:929	arg1	sp					931:932	a Photobacterium sp	914:932	a Photobacterium sp	914:932	We identified a novel α2,6-sialyltransferase from Helicobacter cetorum and compared it to the human ST6Gal1 and a Photobacterium sp.
31281932	2	36	theme	serum	237:241	arg1	half-life					243:251	serum half-life	237:251	serum half-life	237:251	Therapeutic efficacy and serum half-life are particularly important, and these properties rely heavily on the glycosylation state of the protein.
31281932	6	37	theme	novel	818:822	arg1	α2,6-sialyltransferase					824:845	a novel α2,6-sialyltransferase	816:845	a novel α2,6-sialyltransferase	816:845	We identified a novel α2,6-sialyltransferase from Helicobacter cetorum and compared it to the human ST6Gal1 and a Photobacterium sp.
31281932	0	38	theme	therapeutic	57:67	arg1	proteins					69:76	therapeutic proteins	57:76	therapeutic proteins	57:76	Comparison of α2,6-sialyltransferases for sialylation of therapeutic proteins.
31281932	4	39	theme	promising	597:605	arg1	strategy					619:626	a promising and elegant strategy	595:626	a promising and elegant strategy to overcome this problem	595:651	The in vitro modification of therapeutic proteins by recombinant sialyltransferases offers a promising and elegant strategy to overcome this problem.
31281932	3	40	dep	systems	369:375	arg1	produce					380:386	produce	380:386	to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids	377:479	Expression systems to produce authentically fully glycosylated therapeutic proteins with appropriate terminal sialic acids are not yet perfected.
31281932	8	41	theme	different	1167:1175	arg1	proteins					1189:1196	different therapeutic proteins	1167:1196	different therapeutic proteins	1167:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	2	42	theme	protein	349:355	arg1	state					336:340	the glycosylation state	318:340	the glycosylation state of the protein	318:355	Therapeutic efficacy and serum half-life are particularly important, and these properties rely heavily on the glycosylation state of the protein.
31281932	7	43	theme	microtiter-plate-based	996:1017	arg1	assay					1019:1023	a 96-well microtiter-plate-based assay	986:1023	a 96-well microtiter-plate-based assay	986:1023	sialyltransferase using glycoprotein substrates in a 96-well microtiter-plate-based assay.
31281932	5	44	theme	chains	756:761	arg1	completion					731:740	completion	731:740	completion of the glycan chains	731:761	Thus, the detailed expression and characterization of sialyltransferases for completion of the glycan chains is of great interest to the community.
31281932	2	45	theme	Therapeutic	212:222	arg1	efficacy					224:231	Therapeutic efficacy	212:231	Therapeutic efficacy	212:231	Therapeutic efficacy and serum half-life are particularly important, and these properties rely heavily on the glycosylation state of the protein.
31281932	0	46	gly	sialylation	42:52	arg1	proteins					69:76	therapeutic proteins	57:76	therapeutic proteins	57:76	Comparison of α2,6-sialyltransferases for sialylation of therapeutic proteins.
31281932	1	47	theme	numerous	140:147	arg1	diseases					149:156	numerous diseases	140:156	numerous diseases	140:156	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	8	48	theme	recombinant	1051:1061	arg1	catalyst					1118:1125	an excellent catalyst	1105:1125	an excellent catalyst for modification of N-linked glycans of different therapeutic proteins	1105:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	8	48	theme	recombinant	1051:1061	arg1	α2,6-sialyltransferase					1063:1084	the recombinant α2,6-sialyltransferase	1047:1084	the recombinant α2,6-sialyltransferase from H. cetorum	1047:1100	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	1	49	theme	diseases	149:156	arg1	treatment					127:135	the treatment	123:135	the treatment of numerous diseases	123:156	The development of therapeutic proteins for the treatment of numerous diseases is one of the fastest growing areas of biotechnology.
31281932	8	50	link	N-linked	1147:1154	arg1	glycans					1156:1162	N-linked glycans	1147:1162	N-linked glycans of different therapeutic proteins	1147:1196	We demonstrated that the recombinant α2,6-sialyltransferase from H. cetorum is an excellent catalyst for modification of N-linked glycans of different therapeutic proteins.
31281932	2	51	gly	glycosylation	322:334	arg1	protein					349:355	the protein	345:355	the protein	345:355	Therapeutic efficacy and serum half-life are particularly important, and these properties rely heavily on the glycosylation state of the protein.
31281932	6	52	theme	human	896:900	arg1	ST6Gal1					902:908	the human ST6Gal1	892:908	the human ST6Gal1	892:908	We identified a novel α2,6-sialyltransferase from Helicobacter cetorum and compared it to the human ST6Gal1 and a Photobacterium sp.
31281932	7	53	theme	96-well	988:994	arg1	assay					1019:1023	a 96-well microtiter-plate-based assay	986:1023	a 96-well microtiter-plate-based assay	986:1023	sialyltransferase using glycoprotein substrates in a 96-well microtiter-plate-based assay.
31281932	5	54	dep	expression	673:682	arg1	the					660:662	the	660:662	the	660:662	Thus, the detailed expression and characterization of sialyltransferases for completion of the glycan chains is of great interest to the community.
31281932	4	55	theme	proteins	545:552	arg1	modification					517:528	The in vitro modification	504:528	The in vitro modification of therapeutic proteins by recombinant sialyltransferases	504:586	The in vitro modification of therapeutic proteins by recombinant sialyltransferases offers a promising and elegant strategy to overcome this problem.
31281932	0	56	theme	α2,6-sialyltransferases	14:36	arg1	Comparison					0:9	Comparison	0:9	Comparison of α2,6-sialyltransferases for sialylation of therapeutic proteins.	0:77	Comparison of α2,6-sialyltransferases for sialylation of therapeutic proteins.
31275257	6	0	from	degradation	934:944	arg1	crucial					919:925	crucial	919:925	crucial	919:925	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	3	1	theme	biochemical	504:514	arg1	data					516:519	these biochemical data	498:519	these biochemical data	498:519	But yet, considering the fact that uncultured species predominate in the human gut microbiota, these biochemical data are far from exhaustive.
31275257	1	2	link	N-linked	143:150	arg1	glycans					152:158	N-linked glycans	143:158	N-linked glycans	143:158	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	1	2	link	N-linked	143:150	arg1	glycoproteins					117:129	glycoproteins	117:129	glycoproteins	117:129	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	8	3	theme	clones	1295:1300	arg1	ability					1280:1286	the ability	1276:1286	the ability of the clones to degrade human intestinal mucus	1276:1334	This step consisted of lectin binding assays to demonstrate the ability of the clones to degrade human intestinal mucus.
31275257	1	4	theme	crucial	179:185	arg1	source					187:192	a crucial source	177:192	a crucial source of carbon for commensal gut bacteria	177:229	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	8	5	theme	binding	1246:1252	arg1	assays					1254:1259	lectin binding assays	1239:1259	lectin binding assays	1239:1259	This step consisted of lectin binding assays to demonstrate the ability of the clones to degrade human intestinal mucus.
31275257	6	6	theme	clones	891:896	arg1	isolation					874:882	the isolation	870:882	the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase	870:1075	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	4	7	theme	mucin	674:678	arg1	glycans					680:686	harvesting mucin glycans	663:686	harvesting mucin glycans	663:686	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	11	8	theme	gut	1892:1894	arg1	feeding					1905:1911	gut bacteria feeding	1892:1911	gut bacteria feeding	1892:1911	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	7	9	theme	functional	1144:1153	arg1	profiles					1155:1162	their diversified functional profiles	1126:1162	their diversified functional profiles	1126:1162	Thirteen of these clones were selected based on their diversified functional profiles and were further analyzed on a secondary screening.
31275257	6	10	theme	sialidases	980:989	arg1	degradation					934:944	the degradation	930:944	the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase	930:1075	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	8	11	theme	intestinal	1319:1328	arg1	mucus					1330:1334	human intestinal mucus	1313:1334	human intestinal mucus	1313:1334	This step consisted of lectin binding assays to demonstrate the ability of the clones to degrade human intestinal mucus.
31275257	10	12	theme	acid	1696:1699	arg1	metabolism					1701:1710	amino acid metabolism	1690:1710	amino acid metabolism machinery	1690:1720	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	5	13	theme	high-throughput	711:725	arg1	screening					727:735	a high-throughput screening	709:735	a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota	709:812	First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates.
31275257	1	14	theme	gut	218:220	arg1	bacteria					222:229	commensal gut bacteria	208:229	commensal gut bacteria	208:229	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	9	15	theme	motifs	1392:1397	arg1	modification					1362:1373	the structural modification	1347:1373	the structural modification of several mucin motifs, sialylated mucin ones in particular,	1347:1435	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	11	16	theme	feeding	1905:1911	arg1	flexibility					1877:1887	the metabolic flexibility	1863:1887	the metabolic flexibility of gut bacteria feeding both on dietary and human glycans	1863:1945	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	6	17	theme	human	949:953	arg1	O-					955:956	human O-	949:956	human O-	949:956	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	11	18	theme	gut	1836:1838	arg1	microbiome					1840:1849	the gut microbiome	1832:1849	the gut microbiome	1832:1849	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	4	19	used	used	564:567	arg2	we					561:562	we	561:562	we	561:562	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	5	20	theme	library	761:767	arg1	screening					727:735	a high-throughput screening	709:735	a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota	709:812	First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates.
31275257	10	21	theme	metagenomic	1485:1495	arg1	loci					1497:1500	their metagenomic loci	1479:1500	Sequencing their metagenomic loci	1468:1500	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	1	22	dep	O-	136:137	arg1	the					132:134	the	132:134	the	132:134	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	9	23	theme	structural	1351:1360	arg1	modification					1362:1373	the structural modification	1347:1373	the structural modification of several mucin motifs, sialylated mucin ones in particular,	1347:1435	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	9	24	from	ones	1417:1420	arg1	particular					1425:1434	particular	1425:1434	particular	1425:1434	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	1	25	theme	human	81:85	arg1	mucus					98:102	The human Intestinal mucus	77:102	The human Intestinal mucus	77:102	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	9	26	gly	sialylated	1400:1409	arg1	ones					1417:1420	sialylated mucin ones	1400:1420	sialylated mucin ones in particular	1400:1434	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	9	26	gly	sialylated	1400:1409	arg1	motifs					1392:1397	several mucin motifs	1378:1397	several mucin motifs	1378:1397	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	5	27	theme	fosmid	742:747	arg1	library					761:767	a fosmid metagenomic library	740:767	a fosmid metagenomic library constructed from the ileum mucosa microbiota	740:812	First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates.
31275257	10	28	theme	catabolic	1522:1530	arg1	pathways					1532:1539	complex catabolic pathways	1514:1539	complex catabolic pathways	1514:1539	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	5	29	theme	chromogenic	820:830	arg1	substrates					832:841	chromogenic substrates	820:841	chromogenic substrates	820:841	First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates.
31275257	9	30	theme	mucin	1386:1390	arg1	ones					1417:1420	sialylated mucin ones	1400:1420	sialylated mucin ones in particular	1400:1434	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	9	30	theme	mucin	1386:1390	arg1	motifs					1392:1397	several mucin motifs	1378:1397	several mucin motifs	1378:1397	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	0	31	theme	Microbiota	19:28	arg1	Relationships					30:42	Host Microbiota Relationships	14:42	Host Microbiota Relationships	14:42	Investigating Host Microbiota Relationships Through Functional Metagenomics.
31275257	1	32	theme	origin	285:290	arg1	glycans					268:274	dietary glycans	260:274	dietary glycans of plant origin	260:290	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	10	33	theme	complementary	1555:1567	arg1	functions					1569:1577	the complementary functions	1551:1577	the complementary functions	1551:1577	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	33	theme	complementary	1555:1567	arg1	deacetylation					1621:1633	deacetylation	1621:1633	deacetylation	1621:1633	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	33	theme	complementary	1555:1567	arg1	deamination					1640:1650	deamination	1640:1650	deamination	1640:1650	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	33	theme	complementary	1555:1567	arg1	hydrolysis					1609:1618	hydrolysis	1609:1618	hydrolysis	1609:1618	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	33	theme	complementary	1555:1567	arg1	transport					1598:1606	transport	1598:1606	transport	1598:1606	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	5	34	theme	ileum	790:794	arg1	microbiota					803:812	the ileum mucosa microbiota	786:812	the ileum mucosa microbiota	786:812	First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates.
31275257	9	35	theme	mucin	1411:1415	arg1	ones					1417:1420	sialylated mucin ones	1400:1420	sialylated mucin ones in particular	1400:1434	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	9	35	theme	mucin	1411:1415	arg1	motifs					1392:1397	several mucin motifs	1378:1397	several mucin motifs	1378:1397	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	7	36	theme	secondary	1195:1203	arg1	screening					1205:1213	a secondary screening	1193:1213	a secondary screening	1193:1213	Thirteen of these clones were selected based on their diversified functional profiles and were further analyzed on a secondary screening.
31275257	10	37	theme	sensing	1589:1595	arg1	functions					1569:1577	the complementary functions	1551:1577	the complementary functions	1551:1577	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	37	theme	sensing	1589:1595	arg1	deacetylation					1621:1633	deacetylation	1621:1633	deacetylation	1621:1633	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	37	theme	sensing	1589:1595	arg1	deamination					1640:1650	deamination	1640:1650	deamination	1640:1650	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	37	theme	sensing	1589:1595	arg1	hydrolysis					1609:1618	hydrolysis	1609:1618	hydrolysis	1609:1618	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	10	37	theme	sensing	1589:1595	arg1	transport					1598:1606	transport	1598:1606	transport	1598:1606	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	11	38	theme	abundant	1820:1827	arg1	Bacteroides					1758:1768	several Bacteroides and Feacalibacterium species	1750:1797	Bacteroides	1758:1768	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	2	39	theme	dozen	312:316	arg1	enzymes					338:344	a dozen carbohydrate-active enzymes	310:344	a dozen carbohydrate-active enzymes from cultivated mucin degraders	310:376	In recent years, a dozen carbohydrate-active enzymes from cultivated mucin degraders have been characterized.
31275257	11	40	theme	prevalent	1806:1814	arg1	Bacteroides					1758:1768	several Bacteroides and Feacalibacterium species	1750:1797	Bacteroides	1758:1768	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	4	41	theme	new	605:607	arg1	pathways					619:626	new metabolic pathways	605:626	new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans	605:686	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	2	42	theme	cultivated	351:360	arg1	degraders					368:376	cultivated mucin degraders	351:376	cultivated mucin degraders	351:376	In recent years, a dozen carbohydrate-active enzymes from cultivated mucin degraders have been characterized.
31275257	1	43	theme	dietary	260:266	arg1	glycans					268:274	dietary glycans	260:274	dietary glycans of plant origin	260:290	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	6	44	theme	crucial	919:925	arg1	activities					908:917	activities	908:917	activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase	908:1075	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	4	45	theme	functional	569:578	arg1	metagenomics					580:591	functional metagenomics	569:591	functional metagenomics	569:591	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	6	46	from	crucial	919:925	arg1	degradation					934:944	the degradation	930:944	the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase	930:1075	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	11	47	theme	several	1750:1756	arg1	Bacteroides					1758:1768	several Bacteroides and Feacalibacterium species	1750:1797	Bacteroides	1758:1768	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	7	48	theme	diversified	1132:1142	arg1	profiles					1155:1162	their diversified functional profiles	1126:1162	their diversified functional profiles	1126:1162	Thirteen of these clones were selected based on their diversified functional profiles and were further analyzed on a secondary screening.
31275257	8	49	theme	lectin	1239:1244	arg1	assays					1254:1259	lectin binding assays	1239:1259	lectin binding assays	1239:1259	This step consisted of lectin binding assays to demonstrate the ability of the clones to degrade human intestinal mucus.
31275257	2	50	from	degraders	368:376	arg1	enzymes					338:344	a dozen carbohydrate-active enzymes	310:344	a dozen carbohydrate-active enzymes from cultivated mucin degraders	310:376	In recent years, a dozen carbohydrate-active enzymes from cultivated mucin degraders have been characterized.
31275257	4	51	theme	harvesting	663:672	arg1	glycans					680:686	harvesting mucin glycans	663:686	harvesting mucin glycans	663:686	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	11	52	theme	bacteria	1896:1903	arg1	feeding					1905:1911	gut bacteria feeding	1892:1911	gut bacteria feeding	1892:1911	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	2	53	theme	recent	296:301	arg1	years					303:307	recent years	296:307	recent years	296:307	In recent years, a dozen carbohydrate-active enzymes from cultivated mucin degraders have been characterized.
31275257	1	54	theme	carbon	197:202	arg1	source					187:192	a crucial source	177:192	a crucial source of carbon for commensal gut bacteria	177:229	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	8	55	theme	human	1313:1317	arg1	mucus					1330:1334	human intestinal mucus	1313:1334	human intestinal mucus	1313:1334	This step consisted of lectin binding assays to demonstrate the ability of the clones to degrade human intestinal mucus.
31275257	10	56	theme	metabolism	1701:1710	arg1	machinery					1712:1720	amino acid metabolism machinery	1690:1720	amino acid metabolism machinery	1690:1720	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	4	57	from	pathways	619:626	arg1	bacteria					642:649	uncultured bacteria	631:649	uncultured bacteria involved in harvesting mucin glycans	631:686	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	1	58	theme	commensal	208:216	arg1	bacteria					222:229	commensal gut bacteria	208:229	commensal gut bacteria	208:229	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	6	59	theme	N-glycans	962:970	arg1	degradation					934:944	the degradation	930:944	the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase	930:1075	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	4	60	theme	uncultured	631:640	arg1	bacteria					642:649	uncultured bacteria	631:649	uncultured bacteria involved in harvesting mucin glycans	631:686	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	10	61	theme	amino	1690:1694	arg1	metabolism					1701:1710	amino acid metabolism	1690:1710	amino acid metabolism machinery	1690:1720	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	11	62	theme	dietary	1921:1927	arg1	glycans					1939:1945	dietary and human glycans	1921:1945	dietary and human glycans	1921:1945	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	7	63	theme	clones	1096:1101	arg1	clones					1096:1101	these clones	1090:1101	these clones	1090:1101	Thirteen of these clones were selected based on their diversified functional profiles and were further analyzed on a secondary screening.
31275257	7	63	theme	clones	1096:1101	arg1	Thirteen					1078:1085	Thirteen	1078:1085	Thirteen	1078:1085	Thirteen of these clones were selected based on their diversified functional profiles and were further analyzed on a secondary screening.
31275257	6	64	theme	O-	955:956	arg1	degradation					934:944	the degradation	930:944	the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase	930:1075	The screening resulted in the isolation of 124 clones producing activities crucial in the degradation of human O- and N-glycans, namely sialidases, β-D-N-acetyl-glucosaminidase, β-D-N-acetyl-galactosaminidase, and/or β-D-mannosidase.
31275257	11	65	from	microbiome	1840:1849	arg1	abundant					1820:1827	abundant	1820:1827	abundant	1820:1827	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	3	66	theme	human	476:480	arg1	microbiota					486:495	the human gut microbiota	472:495	the human gut microbiota	472:495	But yet, considering the fact that uncultured species predominate in the human gut microbiota, these biochemical data are far from exhaustive.
31275257	5	67	theme	metagenomic	749:759	arg1	library					761:767	a fosmid metagenomic library	740:767	a fosmid metagenomic library constructed from the ileum mucosa microbiota	740:812	First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates.
31275257	1	68	theme	N-linked	143:150	arg1	glycans					152:158	N-linked glycans	143:158	N-linked glycans	143:158	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	1	68	theme	N-linked	143:150	arg1	glycoproteins					117:129	glycoproteins	117:129	glycoproteins	117:129	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	11	69	dep	feeding	1905:1911	arg1	both					1913:1916	both	1913:1916	both	1913:1916	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	11	70	from	abundant	1820:1827	arg1	microbiome					1840:1849	the gut microbiome	1832:1849	the gut microbiome	1832:1849	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	11	71	theme	metabolic	1867:1875	arg1	flexibility					1877:1887	the metabolic flexibility	1863:1887	the metabolic flexibility of gut bacteria feeding both on dietary and human glycans	1863:1945	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	3	72	theme	gut	482:484	arg1	microbiota					486:495	the human gut microbiota	472:495	the human gut microbiota	472:495	But yet, considering the fact that uncultured species predominate in the human gut microbiota, these biochemical data are far from exhaustive.
31275257	1	73	gly	glycoproteins	117:129	arg1	O-					136:137	O-	136:137	O-	136:137	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	1	73	gly	glycoproteins	117:129	arg1	glycans					152:158	N-linked glycans	143:158	N-linked glycans	143:158	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	1	73	gly	glycoproteins	117:129	arg1	glycoproteins					117:129	glycoproteins	117:129	glycoproteins	117:129	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	1	74	theme	Intestinal	87:96	arg1	mucus					98:102	The human Intestinal mucus	77:102	The human Intestinal mucus	77:102	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	3	75	theme	uncultured	438:447	arg1	species					449:455	uncultured species	438:455	uncultured species	438:455	But yet, considering the fact that uncultured species predominate in the human gut microbiota, these biochemical data are far from exhaustive.
31275257	0	76	theme	Host	14:17	arg1	Relationships					30:42	Host Microbiota Relationships	14:42	Host Microbiota Relationships	14:42	Investigating Host Microbiota Relationships Through Functional Metagenomics.
31275257	9	77	theme	several	1378:1384	arg1	ones					1417:1420	sialylated mucin ones	1400:1420	sialylated mucin ones in particular	1400:1434	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	9	77	theme	several	1378:1384	arg1	motifs					1392:1397	several mucin motifs	1378:1397	several mucin motifs	1378:1397	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	10	78	theme	complex	1514:1520	arg1	pathways					1532:1539	complex catabolic pathways	1514:1539	complex catabolic pathways	1514:1539	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	1	79	theme	plant	279:283	arg1	origin					285:290	plant origin	279:290	plant origin	279:290	The human Intestinal mucus is formed by glycoproteins, the O- and N-linked glycans which constitute a crucial source of carbon for commensal gut bacteria, especially when deprived of dietary glycans of plant origin.
31275257	11	80	theme	Feacalibacterium	1774:1789	arg1	species					1791:1797	several Bacteroides and Feacalibacterium species	1750:1797	species	1791:1797	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	0	81	theme	Functional	52:61	arg1	Metagenomics					63:74	Functional Metagenomics	52:74	Functional Metagenomics	52:74	Investigating Host Microbiota Relationships Through Functional Metagenomics.
31275257	9	82	theme	sialylated	1400:1409	arg1	ones					1417:1420	sialylated mucin ones	1400:1420	sialylated mucin ones in particular	1400:1434	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	9	82	theme	sialylated	1400:1409	arg1	motifs					1392:1397	several mucin motifs	1378:1397	several mucin motifs	1378:1397	In total, the structural modification of several mucin motifs, sialylated mucin ones in particular, was evidenced for nine clones.
31275257	5	83	theme	mucosa	796:801	arg1	microbiota					803:812	the ileum mucosa microbiota	786:812	the ileum mucosa microbiota	786:812	First, we performed a high-throughput screening of a fosmid metagenomic library constructed from the ileum mucosa microbiota using chromogenic substrates.
31275257	2	84	theme	carbohydrate-active	318:336	arg1	enzymes					338:344	a dozen carbohydrate-active enzymes	310:344	a dozen carbohydrate-active enzymes from cultivated mucin degraders	310:376	In recent years, a dozen carbohydrate-active enzymes from cultivated mucin degraders have been characterized.
31275257	10	85	theme	glycan	1582:1587	arg1	sensing					1589:1595	glycan sensing	1582:1595	glycan sensing	1582:1595	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	11	86	theme	human	1933:1937	arg1	glycans					1939:1945	dietary and human glycans	1921:1945	dietary and human glycans	1921:1945	These loci are assigned to several Bacteroides and Feacalibacterium species highly prevalent and abundant in the gut microbiome and explain the metabolic flexibility of gut bacteria feeding both on dietary and human glycans.
31275257	10	87	dep	Sequencing	1468:1477	arg1	loci					1497:1500	their metagenomic loci	1479:1500	Sequencing their metagenomic loci	1468:1500	Sequencing their metagenomic loci highlighted complex catabolic pathways involving the complementary functions of glycan sensing, transport, hydrolysis, deacetylation, and deamination, which were sometimes associated with amino acid metabolism machinery.
31275257	4	88	theme	metabolic	609:617	arg1	pathways					619:626	new metabolic pathways	605:626	new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans	605:686	In this study, we used functional metagenomics to identify new metabolic pathways in uncultured bacteria involved in harvesting mucin glycans.
31275257	2	89	theme	mucin	362:366	arg1	degraders					368:376	cultivated mucin degraders	351:376	cultivated mucin degraders	351:376	In recent years, a dozen carbohydrate-active enzymes from cultivated mucin degraders have been characterized.
30988294	2	0	theme	key	369:371	arg1	player					373:378	a key player	367:378	a key player in bacterial cell wall synthesis	367:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	5	1	theme	lipid	826:830	arg1	flipping					832:839	lipid flipping	826:839	lipid flipping	826:839	Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.
30988294	1	2	theme	specialized	268:278	arg1	flippases					280:288	specialized flippases	268:288	specialized flippases	268:288	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	4	3	theme	inward-occluded	676:690	arg1	conformations					711:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations.
30988294	4	4	theme	inward-open	663:673	arg1	conformations					711:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations.
30988294	1	5	link	lipid-linked	199:210	arg1	LLO					229:231	LLO	229:231	LLO	229:231	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	1	5	link	lipid-linked	199:210	arg1	oligosaccharide					212:226	lipid-linked oligosaccharide	199:226	lipid-linked oligosaccharide (LLO) precursors	199:243	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	2	6	theme	wall	398:401	arg1	synthesis					403:411	bacterial cell wall synthesis	383:411	bacterial cell wall synthesis	383:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	7	theme	antibacterials	450:463	arg1	MurJ					291:294	MurJ	291:294	MurJ	291:294	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	7	theme	antibacterials	450:463	arg1	flippase					303:310	the flippase	299:310	the flippase for the lipid-linked peptidoglycan precursor Lipid II	299:364	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	7	theme	antibacterials	450:463	arg1	player					373:378	a key player	367:378	a key player in bacterial cell wall synthesis	367:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	7	theme	antibacterials	450:463	arg1	target					420:425	a target	418:425	a target of recently discovered antibacterials	418:463	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	8	theme	peptidoglycan	333:345	arg1	Lipid					357:361	the lipid-linked peptidoglycan precursor Lipid II	316:364	the lipid-linked peptidoglycan precursor Lipid II	316:364	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	9	theme	cell	393:396	arg1	synthesis					403:411	bacterial cell wall synthesis	383:411	bacterial cell wall synthesis	383:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	10	theme	discovered	439:448	arg1	antibacterials					450:463	recently discovered antibacterials	430:463	recently discovered antibacterials	430:463	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	1	11	theme	many	88:91	arg1	peptidoglycan					130:142	bacterial peptidoglycan	120:142	bacterial peptidoglycan	120:142	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	1	11	theme	many	88:91	arg1	glycans					168:174	eukaryotic N-linked glycans	148:174	eukaryotic N-linked glycans	148:174	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	1	11	theme	many	88:91	arg1	polysaccharides					93:107	many polysaccharides	88:107	many polysaccharides	88:107	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	1	12	theme	lipid-linked	199:210	arg1	LLO					229:231	LLO	229:231	LLO	229:231	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	1	12	theme	lipid-linked	199:210	arg1	oligosaccharide					212:226	lipid-linked oligosaccharide	199:226	lipid-linked oligosaccharide (LLO) precursors	199:243	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	2	13	from	player	373:378	arg1	synthesis					403:411	bacterial cell wall synthesis	383:411	bacterial cell wall synthesis	383:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	1	14	theme	polysaccharides	93:107	arg1	biosynthesis					72:83	The biosynthesis	68:83	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans,	68:175	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	1	15	theme	oligosaccharide	212:226	arg1	precursors					234:243	lipid-linked oligosaccharide (LLO) precursors	199:243	lipid-linked oligosaccharide (LLO) precursors	199:243	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	2	16	theme	lipid-linked	320:331	arg1	Lipid					357:361	the lipid-linked peptidoglycan precursor Lipid II	316:364	the lipid-linked peptidoglycan precursor Lipid II	316:364	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	4	17	theme	crystal	609:615	arg1	structures					617:626	crystal structures	609:626	crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations	609:723	Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations.
30988294	4	18	theme	MurJ	631:634	arg1	structures					617:626	crystal structures	609:626	crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations	609:723	Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations.
30988294	0	19	theme	Lipid	44:48	arg1	MurJ					62:65	the Lipid II flippase MurJ	40:65	the Lipid II flippase MurJ	40:65	Visualizing conformation transitions of the Lipid II flippase MurJ.
30988294	3	20	theme	LLOs	501:504	arg1	mechanism					488:496	the flipping mechanism	475:496	the flipping mechanism of LLOs including Lipid II	475:523	However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information.
30988294	5	21	theme	mutagenesis	740:750	arg1	studies					752:758	mutagenesis studies	740:758	mutagenesis studies	740:758	Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.
30988294	4	22	theme	inward-closed	648:660	arg1	conformations					711:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations.
30988294	2	23	theme	bacterial	383:391	arg1	synthesis					403:411	bacterial cell wall synthesis	383:411	bacterial cell wall synthesis	383:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	3	24	theme	structural	570:579	arg1	information					581:591	structural information	570:591	structural information	570:591	However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information.
30988294	4	25	theme	outward-facing	696:709	arg1	conformations					711:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	inward-closed, inward-open, inward-occluded and outward-facing conformations	648:723	Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations.
30988294	1	26	link	N-linked	159:166	arg1	glycans					168:174	eukaryotic N-linked glycans	148:174	eukaryotic N-linked glycans	148:174	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	0	27	theme	flippase	53:60	arg1	MurJ					62:65	the Lipid II flippase MurJ	40:65	the Lipid II flippase MurJ	40:65	Visualizing conformation transitions of the Lipid II flippase MurJ.
30988294	3	28	theme	information	581:591	arg1	dearth					560:565	a dearth	558:565	a dearth of structural information	558:591	However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information.
30988294	5	29	theme	inhibitors	924:933	arg1	development					909:919	the development	905:919	the development of inhibitors	905:933	Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.
30988294	1	30	theme	N-linked	159:166	arg1	glycans					168:174	eukaryotic N-linked glycans	148:174	eukaryotic N-linked glycans	148:174	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	1	31	theme	bacterial	120:128	arg1	peptidoglycan					130:142	bacterial peptidoglycan	120:142	bacterial peptidoglycan	120:142	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	2	32	link	lipid-linked	320:331	arg1	Lipid					357:361	the lipid-linked peptidoglycan precursor Lipid II	316:364	the lipid-linked peptidoglycan precursor Lipid II	316:364	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	3	33	theme	flipping	479:486	arg1	mechanism					488:496	the flipping mechanism	475:496	the flipping mechanism of LLOs including Lipid II	475:523	However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information.
30988294	1	34	theme	precursors	234:243	arg1	transport					186:194	transport	186:194	transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases	186:288	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	2	35	theme	precursor	347:355	arg1	Lipid					357:361	the lipid-linked peptidoglycan precursor Lipid II	316:364	the lipid-linked peptidoglycan precursor Lipid II	316:364	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	2	36	from	flippase	303:310	arg1	synthesis					403:411	bacterial cell wall synthesis	383:411	bacterial cell wall synthesis	383:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	5	37	theme	conformational	778:791	arg1	transitions					793:803	the conformational transitions	774:803	the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors	774:933	Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.
30988294	5	38	from	transitions	793:803	arg1	MurJ					808:811	MurJ	808:811	MurJ	808:811	Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.
30988294	1	39	theme	eukaryotic	148:157	arg1	glycans					168:174	eukaryotic N-linked glycans	148:174	eukaryotic N-linked glycans	148:174	The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases.
30988294	0	40	theme	MurJ	62:65	arg1	transitions					25:35	conformation transitions	12:35	conformation transitions of the Lipid II flippase MurJ	12:65	Visualizing conformation transitions of the Lipid II flippase MurJ.
30988294	5	41	theme	key	855:857	arg1	ion					859:861	the key ion	851:861	the key ion for function	851:874	Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.
30988294	2	42	from	target	420:425	arg1	synthesis					403:411	bacterial cell wall synthesis	383:411	bacterial cell wall synthesis	383:411	MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials.
30988294	0	43	theme	conformation	12:23	arg1	transitions					25:35	conformation transitions	12:35	conformation transitions of the Lipid II flippase MurJ	12:65	Visualizing conformation transitions of the Lipid II flippase MurJ.
30169966	1	0	theme	dynamic	158:164	arg1	modification					166:177	The dynamic modification	154:177	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation)	154:256	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	6	1	theme	method	1059:1064	arg1	adoption					1042:1049	Broad adoption	1036:1049	Broad adoption of this method by the scientific community	1036:1092	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	8	2	theme	endogenous	1567:1576	arg1	proteins					1578:1585	endogenous proteins	1567:1585	endogenous proteins in any cell or tissue lysate	1567:1614	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	5	3	theme	electrophoresis	967:981	arg1	 that					993:997	sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that	925:997	sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that	925:997	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	7	4	theme	"	1237:1237	arg1	approach					1239:1246	a "click chemistry" approach	1219:1246	a "click chemistry" approach to this method using entirely commercial reagents	1219:1296	Here, we develop a "click chemistry" approach to this method using entirely commercial reagents and confirm the accuracy of the approach using a semisynthetic O-GlcNAcylated protein.
30169966	1	5	link	O-linked	208:215	arg1	O-GlcNAcylation					241:255	O-GlcNAcylation	241:255	O-GlcNAcylation	241:255	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	1	5	link	O-linked	208:215	arg1	-N-acetylglucosamine					219:238	O-linked β -N-acetylglucosamine	208:238	O-linked β -N-acetylglucosamine (O-GlcNAcylation)	208:256	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	2	6	theme	various	316:322	arg1	methods					324:330	various methods	316:330	various methods	316:330	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	6	7	theme	standards	1191:1199	arg1	lack					1126:1129	a lack	1124:1129	a lack of commercially available reagents and well-defined protein standards	1124:1199	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	1	8	theme	many	282:285	arg1	processes					296:304	many cellular processes	282:304	many cellular processes	282:304	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	7	9	theme	commercial	1278:1287	arg1	reagents					1289:1296	entirely commercial reagents	1269:1296	entirely commercial reagents	1269:1296	Here, we develop a "click chemistry" approach to this method using entirely commercial reagents and confirm the accuracy of the approach using a semisynthetic O-GlcNAcylated protein.
30169966	5	10	theme	gel	963:965	arg1	SDS-PAGE					984:991	SDS-PAGE	984:991	SDS-PAGE	984:991	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	5	10	theme	gel	963:965	arg1	electrophoresis					967:981	sodium dodecyl sulfate-polyacrylamide gel electrophoresis	925:981	sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that	925:997	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	1	11	theme	cellular	287:294	arg1	processes					296:304	many cellular processes	282:304	many cellular processes	282:304	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	0	12	theme	O-GlcNAc	110:117	arg1	Stoichiometry					119:131	O-GlcNAc Stoichiometry	110:131	O-GlcNAc Stoichiometry	110:131	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	2	13	dep	mono-	461:465	arg1	i.e.					455:458	i.e., mono-, di-, etc., O-GlcNAcylated	455:492	i.e.	455:458	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	4	14	theme	mass	829:832	arg1	polymers					799:806	polyethylene glycol polymers	779:806	polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins	779:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	4	15	theme	powerful	698:705	arg1	solution					707:714	One powerful solution	694:714	One powerful solution to this limitation	694:733	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	5	16	theme	protein	900:906	arg1	migration					908:916	protein migration	900:916	protein migration	900:916	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	7	17	theme	chemistry	1228:1236	arg1	approach					1239:1246	a "click chemistry" approach	1219:1246	a "click chemistry" approach to this method using entirely commercial reagents	1219:1296	Here, we develop a "click chemistry" approach to this method using entirely commercial reagents and confirm the accuracy of the approach using a semisynthetic O-GlcNAcylated protein.
30169966	8	18	theme	cell	1594:1597	arg1	lysate					1609:1614	any cell or tissue lysate	1590:1614	lysate	1609:1614	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	3	19	theme	given	541:545	arg1	protein					557:563	a given substrate protein	539:563	a given substrate protein	539:563	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	1	20	theme	intracellular	182:194	arg1	proteins					196:203	intracellular proteins	182:203	intracellular proteins	182:203	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	8	21	theme	tissue	1602:1607	arg1	lysate					1609:1614	any cell or tissue lysate	1590:1614	lysate	1609:1614	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	4	22	theme	polyethylene	779:790	arg1	glycol					792:797	polyethylene glycol	779:797	polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins	779:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	1	23	theme	proteins	196:203	arg1	modification					166:177	The dynamic modification	154:177	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation)	154:256	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	6	24	theme	Broad	1036:1040	arg1	adoption					1042:1049	Broad adoption	1036:1049	Broad adoption of this method by the scientific community	1036:1092	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	4	25	theme	chemoenzymatic	748:761	arg1	installation					763:774	the chemoenzymatic installation	744:774	the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins	744:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	8	26	theme	new	1409:1411	arg1	workflow					1437:1444	a new, expedited experimental workflow	1407:1444	a new, expedited experimental workflow	1407:1444	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	4	27	theme	defined	811:817	arg1	mass					829:832	defined molecular mass	811:832	defined molecular mass onto O-GlcNAcylated proteins	811:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	7	28	theme	O-GlcNAcylated	1361:1374	arg1	protein					1376:1382	a semisynthetic O-GlcNAcylated protein	1345:1382	a semisynthetic O-GlcNAcylated protein	1345:1382	Here, we develop a "click chemistry" approach to this method using entirely commercial reagents and confirm the accuracy of the approach using a semisynthetic O-GlcNAcylated protein.
30169966	0	29	theme	Mass	31:34	arg1	Tagging					36:42	Chemoenzymatic Mass Tagging	16:42	Chemoenzymatic Mass Tagging	16:42	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	8	30	from	proteins	1578:1585	arg1	lysate					1609:1614	any cell or tissue lysate	1590:1614	lysate	1609:1614	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	4	31	theme	polymers	799:806	arg1	installation					763:774	the chemoenzymatic installation	744:774	the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins	744:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	1	32	theme	O-linked	208:215	arg1	O-GlcNAcylation					241:255	O-GlcNAcylation	241:255	O-GlcNAcylation	241:255	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	1	32	theme	O-linked	208:215	arg1	-N-acetylglucosamine					219:238	O-linked β -N-acetylglucosamine	208:238	O-linked β -N-acetylglucosamine (O-GlcNAcylation)	208:256	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	0	33	theme	Chemoenzymatic	16:29	arg1	Tagging					36:42	Chemoenzymatic Mass Tagging	16:42	Chemoenzymatic Mass Tagging	16:42	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	8	34	used	utilized	1491:1498	arg2	workflow					1437:1444	a new, expedited experimental workflow	1407:1444	a new, expedited experimental workflow	1407:1444	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	8	34	used	utilized	1491:1498	arg2	methods					1463:1469	standardized methods	1450:1469	standardized methods	1450:1469	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	0	35	theme	Stoichiometry	119:131	arg1	Determination					93:105	the Determination	89:105	the Determination of O-GlcNAc Stoichiometry by Western Blotting	89:151	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	8	36	theme	O-GlcNAc	1531:1538	arg1	stoichiometry					1540:1552	the O-GlcNAc stoichiometry	1527:1552	the O-GlcNAc stoichiometry	1527:1552	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	4	37	theme	glycol	792:797	arg1	polymers					799:806	polyethylene glycol polymers	779:806	polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins	779:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	1	38	theme	β	217:217	arg1	O-GlcNAcylation					241:255	O-GlcNAcylation	241:255	O-GlcNAcylation	241:255	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	1	38	theme	β	217:217	arg1	-N-acetylglucosamine					219:238	O-linked β -N-acetylglucosamine	208:238	O-linked β -N-acetylglucosamine (O-GlcNAcylation)	208:256	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
30169966	5	39	theme	Western	1018:1024	arg1	blotting					1026:1033	Western blotting	1018:1033	Western blotting	1018:1033	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	3	40	theme	functional	674:683	arg1	studies					685:691	functional studies	674:691	functional studies	674:691	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	2	41	dep	state	448:452	arg1	etc.					473:476	etc.	473:476	etc.	473:476	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	2	41	dep	state	448:452	arg1	di-					468:470	di-	468:470	di-	468:470	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	2	41	dep	state	448:452	arg1	mono-					461:465	mono-	461:465	mono-	461:465	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	2	41	dep	state	448:452	arg1	O-GlcNAcylated					479:492	O-GlcNAcylated	479:492	O-GlcNAcylated	479:492	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	8	42	dep	new	1409:1411	arg1	expedited					1414:1422	expedited	1414:1422	expedited	1414:1422	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	0	43	theme	Tagging	36:42	arg1	Optimization					0:11	Optimization	0:11	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.	0:152	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	0	44	theme	Western	136:142	arg1	Blotting					144:151	Western Blotting	136:151	Western Blotting	136:151	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	8	45	theme	experimental	1424:1435	arg1	workflow					1437:1444	a new, expedited experimental workflow	1407:1444	a new, expedited experimental workflow	1407:1444	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	5	46	theme	mass	871:874	arg1	tags					876:879	These "mass tags	864:879	These "mass tags	864:879	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	5	47	from	shifts	890:895	arg1	migration					908:916	protein migration	900:916	protein migration	900:916	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	7	48	theme	approach	1330:1337	arg1	accuracy					1314:1321	the accuracy	1310:1321	the accuracy of the approach using a semisynthetic O-GlcNAcylated protein	1310:1382	Here, we develop a "click chemistry" approach to this method using entirely commercial reagents and confirm the accuracy of the approach using a semisynthetic O-GlcNAcylated protein.
30169966	6	49	theme	available	1147:1155	arg1	reagents					1157:1164	commercially available reagents	1134:1164	commercially available reagents	1134:1164	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	6	50	theme	protein	1183:1189	arg1	standards					1191:1199	well-defined protein standards	1170:1199	well-defined protein standards	1170:1199	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	0	51	theme	Strain-Promoted	47:61	arg1	SPAAC					78:82	SPAAC	78:82	SPAAC	78:82	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	0	51	theme	Strain-Promoted	47:61	arg1	Cycloaddition					63:75	Strain-Promoted Cycloaddition	47:75	Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting	47:151	Optimization of Chemoenzymatic Mass Tagging by Strain-Promoted Cycloaddition (SPAAC) for the Determination of O-GlcNAc Stoichiometry by Western Blotting.
30169966	8	52	theme	standardized	1450:1461	arg1	methods					1463:1469	standardized methods	1450:1469	standardized methods	1450:1469	Our studies establish a new, expedited experimental workflow and standardized methods that can be readily utilized by non-experts to quantify the O-GlcNAc stoichiometry and state on endogenous proteins in any cell or tissue lysate.
30169966	6	53	theme	well-defined	1170:1181	arg1	standards					1191:1199	well-defined protein standards	1170:1199	well-defined protein standards	1170:1199	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	4	54	theme	O-GlcNAcylated	839:852	arg1	proteins					854:861	O-GlcNAcylated proteins	839:861	O-GlcNAcylated proteins	839:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	2	55	theme	O-GlcNAc	356:363	arg1	detection					365:373	O-GlcNAc detection	356:373	O-GlcNAc detection	356:373	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	6	56	theme	reagents	1157:1164	arg1	lack					1126:1129	a lack	1124:1129	a lack of commercially available reagents and well-defined protein standards	1124:1199	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	4	57	theme	molecular	819:827	arg1	mass					829:832	defined molecular mass	811:832	defined molecular mass onto O-GlcNAcylated proteins	811:861	One powerful solution to this limitation involves the chemoenzymatic installation of polyethylene glycol polymers of defined molecular mass onto O-GlcNAcylated proteins.
30169966	3	58	theme	substrate	547:555	arg1	protein					557:563	a given substrate protein	539:563	a given substrate protein	539:563	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	3	59	dep	important	568:576	arg1	prioritizing					646:657	prioritizing	646:657	prioritizing substrates for functional studies	646:691	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	3	59	dep	important	568:576	arg1	understanding					582:594	understanding	582:594	understanding the biology of this critical modification	582:636	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	7	60	theme	semisynthetic	1347:1359	arg1	protein					1376:1382	a semisynthetic O-GlcNAcylated protein	1345:1382	a semisynthetic O-GlcNAcylated protein	1345:1382	Here, we develop a "click chemistry" approach to this method using entirely commercial reagents and confirm the accuracy of the approach using a semisynthetic O-GlcNAcylated protein.
30169966	6	61	theme	scientific	1073:1082	arg1	community					1084:1092	the scientific community	1069:1092	the scientific community	1069:1092	Broad adoption of this method by the scientific community has been limited, however, by a lack of commercially available reagents and well-defined protein standards.
30169966	5	62	theme	sulfate-polyacrylamide	940:961	arg1	SDS-PAGE					984:991	SDS-PAGE	984:991	SDS-PAGE	984:991	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	5	62	theme	sulfate-polyacrylamide	940:961	arg1	electrophoresis					967:981	sodium dodecyl sulfate-polyacrylamide gel electrophoresis	925:981	sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that	925:997	These "mass tags" produce shifts in protein migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that can be detected by Western blotting.
30169966	3	63	theme	critical	616:623	arg1	modification					625:636	this critical modification	611:636	this critical modification	611:636	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	3	64	theme	O-GlcNAcylation	520:534	arg1	levels					510:515	the levels	506:515	the levels of O-GlcNAcylation	506:534	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	2	65	theme	glycosylation	416:428	arg1	stoichiometry					430:442	glycosylation stoichiometry	416:442	glycosylation stoichiometry	416:442	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	7	66	theme	click	1222:1226	arg1	approach					1239:1246	a "click chemistry" approach	1219:1246	a "click chemistry" approach to this method using entirely commercial reagents	1219:1296	Here, we develop a "click chemistry" approach to this method using entirely commercial reagents and confirm the accuracy of the approach using a semisynthetic O-GlcNAcylated protein.
30169966	3	67	theme	modification	625:636	arg1	biology					600:606	the biology	596:606	the biology of this critical modification	596:636	Measuring the levels of O-GlcNAcylation on a given substrate protein is important for understanding the biology of this critical modification and for prioritizing substrates for functional studies.
30169966	2	68	theme	few	386:388	arg1	techniques					390:399	few techniques	386:399	few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated)	386:493	Although various methods have been developed for O-GlcNAc detection, there are few techniques for monitoring glycosylation stoichiometry and state (i.e., mono-, di-, etc., O-GlcNAcylated).
30169966	1	69	theme	critical	264:271	arg1	roles					273:277	critical roles	264:277	critical roles	264:277	The dynamic modification of intracellular proteins by O-linked β -N-acetylglucosamine (O-GlcNAcylation) plays critical roles in many cellular processes.
31640124	1	0	theme	health	130:135	arg1	virus					98:102	Zika virus	93:102	Zika virus (ZIKV)	93:109	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	0	theme	health	130:135	arg1	issue					137:141	a global public health issue	114:141	a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults	114:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	0	1	theme	Pathogenic	71:80	arg1	Potential					82:90	Pathogenic Potential	71:90	Pathogenic Potential	71:90	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	3	2	theme	different	572:580	arg1	cells					582:586	different cells	572:586	different cells	572:586	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	2	3	gly	glycosylation	261:273	arg1	protein					295:301	its envelope (E) protein	278:301	its envelope (E) protein	278:301	ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines.
31640124	3	4	theme	information	469:479	arg1	lack					454:457	a lack	452:457	a lack of proper information about Asn-linked (N-glycans) on ZIKV E	452:518	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	6	5	theme	various	1060:1066	arg1	strains					1068:1074	various strains	1060:1074	various strains	1060:1074	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	4	6	theme	complex	671:677	arg1	N-glycans					679:687	oligomannose, hybrid and complex N-glycans	646:687	N-glycans	679:687	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	3	7	from	information	469:479	arg1	E					518:518	ZIKV E	513:518	ZIKV E	513:518	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	2	8	theme	host	320:323	arg1	receptors					330:338	host cell receptors	320:338	host cell receptors	320:338	ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines.
31640124	5	9	theme	ZIKV	799:802	arg1	features					787:794	the glycomic features	774:794	the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV	774:981	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	10	theme	glycomic	778:785	arg1	features					787:794	the glycomic features	774:794	the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV	774:981	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	4	11	theme	nature	715:720	arg1	N-glycans					679:687	oligomannose, hybrid and complex N-glycans	646:687	N-glycans	679:687	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	5	12	dep	mediate	951:957	arg1	as					897:898	as	897:898	as	897:898	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	12	dep	mediate	951:957	arg1	lectins					924:930	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	12	dep	mediate	951:957	arg1	L-SIGN					944:949	L-SIGN	944:949	L-SIGN	944:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	12	dep	mediate	951:957	arg1	DC-SIGN					932:938	DC-SIGN	932:938	DC-SIGN	932:938	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	1	13	theme	due	143:145	arg1	virus					98:102	Zika virus	93:102	Zika virus (ZIKV)	93:109	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	13	theme	due	143:145	arg1	issue					137:141	a global public health issue	114:141	a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults	114:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	0	14	from	Important	31:39	arg1	Interaction					55:65	Host-Virus Interaction	44:65	Host-Virus Interaction	44:65	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	0	14	from	Important	31:39	arg1	Potential					82:90	Pathogenic Potential	71:90	Pathogenic Potential	71:90	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	6	15	theme	ZIKV	1050:1053	arg1	E					1055:1055	ZIKV E	1050:1055	ZIKV E of various strains and their functional significance	1050:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	4	16	theme	heterogeneous	701:713	arg1	nature					715:720	a highly heterogeneous nature	692:720	a highly heterogeneous nature	692:720	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	6	17	theme	detailed	1017:1024	arg1	mapping					1026:1032	the first detailed mapping	1007:1032	the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance	1007:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	5	18	theme	ZIKV	841:844	arg1	N-glycans					846:854	ZIKV N-glycans	841:854	ZIKV N-glycans	841:854	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	6	19	theme	first	1011:1015	arg1	mapping					1026:1032	the first detailed mapping	1007:1032	the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance	1007:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	2	20	theme	E	292:292	arg1	protein					295:301	its envelope (E) protein	278:301	its envelope (E) protein	278:301	ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines.
31640124	4	21	theme	E	603:603	arg1	proteins					605:612	ZIKV E proteins	598:612	ZIKV E proteins	598:612	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	1	22	theme	Zika	93:96	arg1	ZIKV					105:108	ZIKV	105:108	ZIKV	105:108	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	22	theme	Zika	93:96	arg1	virus					98:102	Zika virus	93:102	Zika virus (ZIKV)	93:109	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	22	theme	Zika	93:96	arg1	issue					137:141	a global public health issue	114:141	a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults	114:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	4	23	theme	ZIKV	598:601	arg1	proteins					605:612	ZIKV E proteins	598:612	ZIKV E proteins	598:612	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	0	24	theme	Virus	22:26	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation of Zika Virus	0:26	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	3	25	from	lack	454:457	arg1	E					518:518	ZIKV E	513:518	ZIKV E	513:518	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	2	26	theme	envelope	282:289	arg1	protein					295:301	its envelope (E) protein	278:301	its envelope (E) protein	278:301	ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines.
31640124	3	27	theme	ZIKV	533:536	arg1	E					538:538	ZIKV E	533:538	ZIKV E of various strains derived from different cells	533:586	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	0	28	theme	Zika	17:20	arg1	Virus					22:26	Zika Virus	17:26	Zika Virus	17:26	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	5	29	theme	mannose-specific	900:915	arg1	lectins					924:930	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	29	theme	mannose-specific	900:915	arg1	L-SIGN					944:949	L-SIGN	944:949	L-SIGN	944:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	29	theme	mannose-specific	900:915	arg1	DC-SIGN					932:938	DC-SIGN	932:938	DC-SIGN	932:938	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	0	30	from	Potential	82:90	arg1	Important					31:39	Important	31:39	Important	31:39	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	3	31	theme	ZIKV	513:516	arg1	E					518:518	ZIKV E	513:518	ZIKV E	513:518	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	1	32	theme	severe	171:176	arg1	disorders					192:200	severe developmental disorders	171:200	severe developmental disorders in infants	171:211	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	6	33	theme	N-glycans	1037:1045	arg1	mapping					1026:1032	the first detailed mapping	1007:1032	the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance	1007:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	1	34	from	disorders	230:238	arg1	adults					243:248	adults	243:248	adults	243:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	34	from	disorders	230:238	arg1	infants					205:211	infants	205:211	infants	205:211	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	5	35	dep	lectins	924:930	arg1	lectins					924:930	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	35	dep	lectins	924:930	arg1	L-SIGN					944:949	L-SIGN	944:949	L-SIGN	944:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	35	dep	lectins	924:930	arg1	DC-SIGN					932:938	DC-SIGN	932:938	DC-SIGN	932:938	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	0	36	gly	Glycosylation	0:12	arg1	Virus					22:26	Zika Virus	17:26	Zika Virus	17:26	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	1	37	theme	developmental	178:190	arg1	disorders					192:200	severe developmental disorders	171:200	severe developmental disorders in infants	171:211	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	5	38	theme	Host	723:726	arg1	glycans					741:747	Host cell surface glycans	723:747	Host cell surface glycans	723:747	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	39	theme	host	959:962	arg1	entry					969:973	host cell entry	959:973	host cell entry of ZIKV	959:981	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	0	40	theme	Host-Virus	44:53	arg1	Interaction					55:65	Host-Virus Interaction	44:65	Host-Virus Interaction	44:65	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	0	41	from	Interaction	55:65	arg1	Important					31:39	Important	31:39	Important	31:39	Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential.
31640124	5	42	theme	cell	964:967	arg1	entry					969:973	host cell entry	959:973	host cell entry of ZIKV	959:981	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	1	43	from	disorders	192:200	arg1	adults					243:248	adults	243:248	adults	243:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	43	from	disorders	192:200	arg1	infants					205:211	infants	205:211	infants	205:211	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	4	44	theme	oligomannose	646:657	arg1	N-glycans					679:687	oligomannose, hybrid and complex N-glycans	646:687	N-glycans	679:687	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	5	45	theme	surface	733:739	arg1	glycans					741:747	Host cell surface glycans	723:747	Host cell surface glycans	723:747	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	46	dep	ZIKV	799:802	arg1	E.					804:805	ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV	799:981	ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV	799:981	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	46	dep	ZIKV	799:802	arg1	observed					827:834	observed	827:834	observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV	827:981	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	1	47	with	association	154:164	arg1	disorders					230:238	neurological disorders	217:238	neurological disorders in adults	217:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	47	with	association	154:164	arg1	disorders					192:200	severe developmental disorders	171:200	severe developmental disorders in infants	171:211	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	6	48	theme	strains	1068:1074	arg1	E					1055:1055	ZIKV E	1050:1055	ZIKV E of various strains and their functional significance	1050:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	3	49	theme	proper	462:467	arg1	information					469:479	proper information	462:479	proper information about Asn-linked (N-glycans) on ZIKV E	462:518	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	3	50	attach	derived	559:565	arg1	cells					582:586	different cells	572:586	different cells	572:586	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	3	50	attach	derived	559:565	arg2	strains					551:557	various strains	543:557	various strains derived from different cells	543:586	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	5	51	theme	ZIKV	978:981	arg1	entry					969:973	host cell entry	959:973	host cell entry of ZIKV	959:981	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	3	52	theme	strains	551:557	arg1	E					538:538	ZIKV E	533:538	ZIKV E of various strains derived from different cells	533:586	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	2	53	theme	protein	295:301	arg1	glycosylation					261:273	glycosylation	261:273	glycosylation of its envelope (E) protein	261:301	ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines.
31640124	5	54	theme	viral	877:881	arg1	pathogenesis					883:894	viral pathogenesis	877:894	viral pathogenesis	877:894	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	55	theme	C-type	917:922	arg1	lectins					924:930	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	mannose-specific C-type lectins DC-SIGN and L-SIGN	900:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	55	theme	C-type	917:922	arg1	L-SIGN					944:949	L-SIGN	944:949	L-SIGN	944:949	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	5	55	theme	C-type	917:922	arg1	DC-SIGN					932:938	DC-SIGN	932:938	DC-SIGN	932:938	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	6	56	from	mapping	1026:1032	arg1	E					1055:1055	ZIKV E	1050:1055	ZIKV E of various strains and their functional significance	1050:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	1	57	theme	public	123:128	arg1	virus					98:102	Zika virus	93:102	Zika virus (ZIKV)	93:109	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	57	theme	public	123:128	arg1	issue					137:141	a global public health issue	114:141	a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults	114:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	3	58	from	E	518:518	arg1	lack					454:457	a lack	452:457	a lack of proper information about Asn-linked (N-glycans) on ZIKV E	452:518	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	4	59	theme	hybrid	660:665	arg1	N-glycans					679:687	oligomannose, hybrid and complex N-glycans	646:687	N-glycans	679:687	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	4	60	dep	found	592:596	arg1	modified					632:639	modified	632:639	found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature	592:720	We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature.
31640124	6	61	theme	functional	1086:1095	arg1	significance					1097:1108	their functional significance	1080:1108	their functional significance	1080:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	1	62	theme	global	116:121	arg1	virus					98:102	Zika virus	93:102	Zika virus (ZIKV)	93:109	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	1	62	theme	global	116:121	arg1	issue					137:141	a global public health issue	114:141	a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults	114:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31640124	6	63	theme	significance	1097:1108	arg1	E					1055:1055	ZIKV E	1050:1055	ZIKV E of various strains and their functional significance	1050:1108	Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.
31640124	5	64	theme	cell	728:731	arg1	glycans					741:747	Host cell surface glycans	723:747	Host cell surface glycans	723:747	Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV.
31640124	3	65	theme	various	543:549	arg1	strains					551:557	various strains	543:557	various strains derived from different cells	543:586	Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells.
31640124	2	66	theme	cell	325:328	arg1	receptors					330:338	host cell receptors	320:338	host cell receptors	320:338	ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines.
31640124	1	67	theme	neurological	217:228	arg1	disorders					230:238	neurological disorders	217:238	neurological disorders in adults	217:248	Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults.
31000023	5	0	theme	2-mM	651:654	arg1	Cu2+					662:665	2-mM Zn2+, Cu2+, or Ba2+ ions	651:679	Cu2+	662:665	The activity of the glucanase was 27 ± 2.6% enhanced by 2-mM Mn2+ ions and inhibited by 40-50% using 2-mM Zn2+, Cu2+, or Ba2+ ions.
31000023	7	1	theme	necrosis	1009:1016	arg1	factor					1018:1023	tumor necrosis factor α	1003:1025	tumor necrosis factor α	1003:1025	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	8	2	theme	food	1117:1120	arg1	industry					1122:1129	the food industry	1113:1129	the food industry	1113:1129	It might be used as a bifunctional additive for the food industry.
31000023	5	3	theme	Zn2+	656:659	arg1	Cu2+					662:665	2-mM Zn2+, Cu2+, or Ba2+ ions	651:679	Cu2+	662:665	The activity of the glucanase was 27 ± 2.6% enhanced by 2-mM Mn2+ ions and inhibited by 40-50% using 2-mM Zn2+, Cu2+, or Ba2+ ions.
31000023	5	4	theme	Mn2+	611:614	arg1	ions					616:619	2-mM Mn2+ ions	606:619	2-mM Mn2+ ions	606:619	The activity of the glucanase was 27 ± 2.6% enhanced by 2-mM Mn2+ ions and inhibited by 40-50% using 2-mM Zn2+, Cu2+, or Ba2+ ions.
31000023	8	5	used	used	1077:1080	arg2	It					1065:1066	It	1065:1066	It	1065:1066	It might be used as a bifunctional additive for the food industry.
31000023	8	5	used	used	1077:1080	arg2	additive					1100:1107	additive	1100:1107	additive	1100:1107	It might be used as a bifunctional additive for the food industry.
31000023	2	6	theme	specific	305:312	arg1	glycoprotein					221:232	a glycoprotein	219:232	a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan	219:292	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	2	6	theme	specific	305:312	arg1	It					198:199	It	198:199	It	198:199	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	2	6	theme	specific	305:312	arg1	activity					314:321	specific activity	305:321	specific activity of 90.01 ± 1.2 U/mg against laminarin	305:359	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	5	7	dep	enhanced	594:601	arg1	%					592:592	27 ± 2.6%	584:592	27 ± 2.6%	584:592	The activity of the glucanase was 27 ± 2.6% enhanced by 2-mM Mn2+ ions and inhibited by 40-50% using 2-mM Zn2+, Cu2+, or Ba2+ ions.
31000023	2	8	link	O-linked	278:285	arg1	glycan					287:292	O-linked glycan	278:292	O-linked glycan	278:292	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	0	9	theme	immune-enhancing	87:102	arg1	effects					104:110	its immune-enhancing effects	83:110	its immune-enhancing effects	83:110	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	4	10	theme	glucanase	491:499	arg1	parameter					474:482	The affinity parameter	461:482	The affinity parameter of the glucanase using laminarin	461:515	The affinity parameter of the glucanase using laminarin was determined as Kd = 13.09 μM.
31000023	4	10	theme	glucanase	491:499	arg1	Kd = 13.09 μM					535:547	Kd = 13.09 μM	535:547	Kd = 13.09 μM	535:547	The affinity parameter of the glucanase using laminarin was determined as Kd = 13.09 μM.
31000023	1	11	from	inflata	147:153	arg1	β-1,3-glucanase					121:135	A novel β-1,3-glucanase	113:135	A novel β-1,3-glucanase from Arca inflata	113:153	A novel β-1,3-glucanase from Arca inflata was purified using chromatography methods.
31000023	7	12	theme	immune-enhancing	868:883	arg1	effects					885:891	immune-enhancing effects	868:891	immune-enhancing effects	868:891	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	7	13	theme	nitric	989:994	arg1	oxide					996:1000	nitric oxide	989:1000	nitric oxide	989:1000	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	1	14	theme	chromatography	174:187	arg1	methods					189:195	chromatography methods	174:195	chromatography methods	174:195	A novel β-1,3-glucanase from Arca inflata was purified using chromatography methods.
31000023	7	15	theme	RAW264.7	1049:1056	arg1	cells					1058:1062	RAW264.7 cells	1049:1062	RAW264.7 cells	1049:1062	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	2	16	theme	90.01 ± 1.2 U/mg	326:341	arg1	glycoprotein					221:232	a glycoprotein	219:232	a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan	219:292	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	2	16	theme	90.01 ± 1.2 U/mg	326:341	arg1	It					198:199	It	198:199	It	198:199	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	2	16	theme	90.01 ± 1.2 U/mg	326:341	arg1	activity					314:321	specific activity	305:321	specific activity of 90.01 ± 1.2 U/mg against laminarin	305:359	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	2	17	gly	glycoprotein	221:232	arg1	glycoprotein					221:232	a glycoprotein	219:232	a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan	219:292	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	2	17	gly	glycoprotein	221:232	arg1	It					198:199	It	198:199	It	198:199	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	2	17	gly	glycoprotein	221:232	arg1	activity					314:321	specific activity	305:321	specific activity of 90.01 ± 1.2 U/mg against laminarin	305:359	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	5	18	theme	2-mM	606:609	arg1	ions					616:619	2-mM Mn2+ ions	606:619	2-mM Mn2+ ions	606:619	The activity of the glucanase was 27 ± 2.6% enhanced by 2-mM Mn2+ ions and inhibited by 40-50% using 2-mM Zn2+, Cu2+, or Ba2+ ions.
31000023	7	19	theme	oxide	996:1000	arg1	release					978:984	the release	974:984	the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells	974:1062	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	4	20	theme	affinity	465:472	arg1	parameter					474:482	The affinity parameter	461:482	The affinity parameter of the glucanase using laminarin	461:515	The affinity parameter of the glucanase using laminarin was determined as Kd = 13.09 μM.
31000023	4	20	theme	affinity	465:472	arg1	Kd = 13.09 μM					535:547	Kd = 13.09 μM	535:547	Kd = 13.09 μM	535:547	The affinity parameter of the glucanase using laminarin was determined as Kd = 13.09 μM.
31000023	0	21	theme	novel	39:43	arg1	β-1,3-glucanase					45:59	a novel β-1,3-glucanase	37:59	a novel β-1,3-glucanase	37:59	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	2	22	theme	%	250:250	arg1	content					265:271	23.65% carbohydrate content	245:271	23.65% carbohydrate content	245:271	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	0	23	from	inflata	71:77	arg1	characterization					17:32	characterization	17:32	characterization	17:32	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	0	23	from	inflata	71:77	arg1	Purification					0:11	Purification	0:11	Purification	0:11	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	2	24	theme	23.65	245:249	arg1	%					250:250	%	250:250	%	250:250	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	7	25	theme	interleukin-6	1032:1044	arg1	release					978:984	the release	974:984	the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells	974:1062	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	3	26	theme	glucanase	417:425	arg1	activity					401:408	the activity	397:408	the activity of the glucanase	397:425	The optimal pH and temperature for the activity of the glucanase were 6.0 and 40 °C, respectively.
31000023	3	27	dep	pH	374:375	arg1	The					362:364	The	362:364	The	362:364	The optimal pH and temperature for the activity of the glucanase were 6.0 and 40 °C, respectively.
31000023	5	28	theme	glucanase	570:578	arg1	activity					554:561	The activity	550:561	The activity of the glucanase	550:578	The activity of the glucanase was 27 ± 2.6% enhanced by 2-mM Mn2+ ions and inhibited by 40-50% using 2-mM Zn2+, Cu2+, or Ba2+ ions.
31000023	1	29	theme	novel	115:119	arg1	β-1,3-glucanase					121:135	A novel β-1,3-glucanase	113:135	A novel β-1,3-glucanase from Arca inflata	113:153	A novel β-1,3-glucanase from Arca inflata was purified using chromatography methods.
31000023	0	30	theme	β-1,3-glucanase	45:59	arg1	characterization					17:32	characterization	17:32	characterization	17:32	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	0	30	theme	β-1,3-glucanase	45:59	arg1	Purification					0:11	Purification	0:11	Purification	0:11	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	5	31	theme	Ba2+	671:674	arg1	ions					676:679	2-mM Zn2+, Cu2+, or Ba2+ ions	651:679	ions	676:679	The activity of the glucanase was 27 ± 2.6% enhanced by 2-mM Mn2+ ions and inhibited by 40-50% using 2-mM Zn2+, Cu2+, or Ba2+ ions.
31000023	2	32	theme	O-linked	278:285	arg1	glycan					287:292	O-linked glycan	278:292	O-linked glycan	278:292	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	7	33	theme	tumor	1003:1007	arg1	factor					1018:1023	tumor necrosis factor α	1003:1025	tumor necrosis factor α	1003:1025	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	0	34	from	effects	104:110	arg1	characterization					17:32	characterization	17:32	characterization	17:32	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	0	34	from	effects	104:110	arg1	Purification					0:11	Purification	0:11	Purification	0:11	Purification and characterization of a novel β-1,3-glucanase from Arca inflata and its immune-enhancing effects.
31000023	7	35	theme	factor	1018:1023	arg1	release					978:984	the release	974:984	the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells	974:1062	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	7	36	from	release	978:984	arg1	cells					1058:1062	RAW264.7 cells	1049:1062	RAW264.7 cells	1049:1062	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	7	37	theme	phagocytic	926:935	arg1	activity					937:944	the phagocytic activity	922:944	the phagocytic activity of macrophages	922:959	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	6	38	theme	cleavage	716:723	arg1	mode					725:728	an endo-type cleavage mode	703:728	an endo-type cleavage mode	703:728	The glucanase showed an endo-type cleavage mode and hydrolyzed laminarin into glucoses, disaccharides, trioligosaccharides, and tetraoligosaccharides.
31000023	7	39	theme	macrophages	949:959	arg1	activity					937:944	the phagocytic activity	922:944	the phagocytic activity of macrophages	922:959	Otherwise, the glucanase exhibited immune-enhancing effects via significantly increasing the phagocytic activity of macrophages and inducing the release of nitric oxide, tumor necrosis factor α, and interleukin-6 in RAW264.7 cells.
31000023	3	40	theme	optimal	366:372	arg1	pH					374:375	optimal pH	366:375	optimal pH	366:375	The optimal pH and temperature for the activity of the glucanase were 6.0 and 40 °C, respectively.
31000023	2	41	theme	carbohydrate	252:263	arg1	content					265:271	23.65% carbohydrate content	245:271	23.65% carbohydrate content	245:271	It was determined as a glycoprotein comprising 23.65% carbohydrate content with O-linked glycan and showed specific activity of 90.01 ± 1.2 U/mg against laminarin.
31000023	6	42	theme	endo-type	706:714	arg1	mode					725:728	an endo-type cleavage mode	703:728	an endo-type cleavage mode	703:728	The glucanase showed an endo-type cleavage mode and hydrolyzed laminarin into glucoses, disaccharides, trioligosaccharides, and tetraoligosaccharides.
30420690	8	0	theme	significant	1168:1178	arg1	decline					1180:1186	a significant decline	1166:1186	a significant decline in GLI activity	1166:1202	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	10	1	theme	drug	1537:1540	arg1	resistance					1542:1551	drug resistance	1537:1551	drug resistance	1537:1551	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	9	2	theme	pathway	1404:1410	arg1	activity					1375:1382	elevated transcriptional activity	1350:1382	elevated transcriptional activity of the Hedgehog/GLI pathway	1350:1410	Cumulatively, our results suggest that elevated glucose conditions upregulate chemoresistance through elevated transcriptional activity of the Hedgehog/GLI pathway.
30420690	2	3	theme	key	369:371	arg1	ABCB1					399:403	ABCB1	399:403	ABCB1	399:403	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	3	theme	key	369:371	arg1	proteins					389:396	key drug resistance proteins	369:396	key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1)	369:429	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	3	theme	key	369:371	arg1	ERCC1					413:417	ERCC1	413:417	ERCC1	413:417	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	3	theme	key	369:371	arg1	XRCC1					424:428	XRCC1	424:428	XRCC1	424:428	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	3	theme	key	369:371	arg1	ABCG2					406:410	ABCG2	406:410	ABCG2	406:410	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	5	4	from	decrease	811:818	arg1	activity					827:834	GLI activity	823:834	GLI activity	823:834	The activity of GLI was enhanced when O-GlcNAcase was inhibited, while inhibiting O-GlcNAc transferase caused a decrease in GLI activity.
30420690	9	5	theme	elevated	1350:1357	arg1	activity					1375:1382	elevated transcriptional activity	1350:1382	elevated transcriptional activity of the Hedgehog/GLI pathway	1350:1410	Cumulatively, our results suggest that elevated glucose conditions upregulate chemoresistance through elevated transcriptional activity of the Hedgehog/GLI pathway.
30420690	9	6	theme	transcriptional	1359:1373	arg1	activity					1375:1382	elevated transcriptional activity	1350:1382	elevated transcriptional activity of the Hedgehog/GLI pathway	1350:1410	Cumulatively, our results suggest that elevated glucose conditions upregulate chemoresistance through elevated transcriptional activity of the Hedgehog/GLI pathway.
30420690	4	7	theme	transcriptional	673:687	arg1	activity					689:696	their transcriptional activity	667:696	their transcriptional activity	667:696	This modification functionally enhanced their transcriptional activity.
30420690	6	8	theme	biosynthetic	1006:1017	arg1	pathways					1019:1026	biosynthetic pathways	1006:1026	biosynthetic pathways	1006:1026	The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways.
30420690	5	9	theme	GLI	715:717	arg1	activity					703:710	The activity	699:710	The activity of GLI	699:717	The activity of GLI was enhanced when O-GlcNAcase was inhibited, while inhibiting O-GlcNAc transferase caused a decrease in GLI activity.
30420690	0	10	from	O-GlcNAcylation	0:14	arg1	conditions					62:71	hyperglycemic conditions	48:71	hyperglycemic conditions	48:71	O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity.
30420690	8	11	theme	GLI	1191:1193	arg1	activity					1195:1202	GLI activity	1191:1202	GLI activity	1191:1202	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	3	12	mod	modified	598:605	arg1	factors					570:576	the Hedgehog pathway transcription factors	535:576	the Hedgehog pathway transcription factors	535:576	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	12	mod	modified	598:605	arg1	GLI2					588:591	GLI2	588:591	GLI2	588:591	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	12	mod	modified	598:605	arg3	O-GlcNAcylation					610:624	O-GlcNAcylation	610:624	O-GlcNAcylation	610:624	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	12	mod	modified	598:605	arg1	GLI1					579:582	GLI1	579:582	GLI1	579:582	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	10	13	theme	cancer	1514:1519	arg1	progression					1521:1531	cancer progression	1514:1531	cancer progression	1514:1531	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	1	14	theme	tumor	180:184	arg1	cell					186:189	tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis	180:273	cell	186:189	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	6	15	theme	intermediates	988:1000	arg1	availability					961:972	the availability	957:972	the availability of glycolytic intermediates for biosynthetic pathways	957:1026	The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways.
30420690	10	16	theme	cancer	1563:1568	arg1	progression					1521:1531	cancer progression	1514:1531	cancer progression	1514:1531	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	10	16	theme	cancer	1563:1568	arg1	resistance					1542:1551	drug resistance	1537:1551	drug resistance	1537:1551	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	10	17	theme	factors	1469:1475	arg1	O-GlcNAcylation					1428:1442	O-GlcNAcylation	1428:1442	O-GlcNAcylation of the GLI transcription factors	1428:1475	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	3	18	theme	glucose	496:502	arg1	conditions					504:513	elevated glucose conditions	487:513	elevated glucose conditions	487:513	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	8	19	theme	resistance	1227:1236	arg1	proteins					1238:1245	drug resistance proteins	1222:1245	drug resistance proteins	1222:1245	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	9	20	theme	elevated	1287:1294	arg1	conditions					1304:1313	elevated glucose conditions	1287:1313	elevated glucose conditions	1287:1313	Cumulatively, our results suggest that elevated glucose conditions upregulate chemoresistance through elevated transcriptional activity of the Hedgehog/GLI pathway.
30420690	9	21	theme	Hedgehog/GLI	1391:1402	arg1	pathway					1404:1410	the Hedgehog/GLI pathway	1387:1410	the Hedgehog/GLI pathway	1387:1410	Cumulatively, our results suggest that elevated glucose conditions upregulate chemoresistance through elevated transcriptional activity of the Hedgehog/GLI pathway.
30420690	10	22	theme	breast	1556:1561	arg1	cancer					1563:1568	breast cancer	1556:1568	breast cancer	1556:1568	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	8	23	theme	drug	1222:1225	arg1	proteins					1238:1245	drug resistance proteins	1222:1245	drug resistance proteins	1222:1245	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	6	24	theme	conditions	875:884	arg1	impact					851:856	The metabolic impact	837:856	The metabolic impact of hyperglycemic conditions	837:884	The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways.
30420690	0	25	theme	Hedgehog	82:89	arg1	activity					91:98	Hedgehog activity	82:98	Hedgehog activity	82:98	O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity.
30420690	6	26	theme	glycolytic	977:986	arg1	intermediates					988:1000	glycolytic intermediates	977:1000	glycolytic intermediates	977:1000	The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways.
30420690	2	27	theme	glucose	327:333	arg1	conditions					304:313	conditions	304:313	conditions of elevated glucose	304:333	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	28	theme	proteins	389:396	arg1	expression					355:364	increased expression	345:364	increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway	345:481	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	0	29	theme	transcription	23:35	arg1	factors					37:43	GLI transcription factors	19:43	GLI transcription factors	19:43	O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity.
30420690	10	30	theme	novel	1486:1490	arg1	target					1492:1497	a novel target	1484:1497	a novel target	1484:1497	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	2	31	theme	elevated	318:325	arg1	glucose					327:333	elevated glucose	318:333	elevated glucose	318:333	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	1	32	theme	epigenetic	216:225	arg1	changes					227:233	epigenetic changes	216:233	epigenetic changes	216:233	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	1	33	dep	cell	186:189	arg1	survival					191:198	survival	191:198	survival	191:198	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	7	34	theme	GLI	1104:1106	arg1	activity					1108:1115	GLI activity	1104:1115	GLI activity	1104:1115	Interestingly, under elevated glucose conditions, PKM2 directly influenced GLI activity.
30420690	6	35	theme	hyperglycemic	861:873	arg1	conditions					875:884	hyperglycemic conditions	861:884	hyperglycemic conditions	861:884	The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways.
30420690	8	36	from	decline	1180:1186	arg1	activity					1195:1202	GLI activity	1191:1202	GLI activity	1191:1202	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	3	37	theme	Hedgehog	539:546	arg1	factors					570:576	the Hedgehog pathway transcription factors	535:576	the Hedgehog pathway transcription factors	535:576	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	37	theme	Hedgehog	539:546	arg1	GLI2					588:591	GLI2	588:591	GLI2	588:591	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	37	theme	Hedgehog	539:546	arg1	GLI1					579:582	GLI1	579:582	GLI1	579:582	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	0	38	theme	factors	37:43	arg1	O-GlcNAcylation					0:14	O-GlcNAcylation	0:14	O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions	0:71	O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity.
30420690	5	39	theme	inhibiting	770:779	arg1	transferase					790:800	inhibiting O-GlcNAc transferase	770:800	inhibiting O-GlcNAc transferase	770:800	The activity of GLI was enhanced when O-GlcNAcase was inhibited, while inhibiting O-GlcNAc transferase caused a decrease in GLI activity.
30420690	8	40	theme	proteins	1238:1245	arg1	decline					1180:1186	a significant decline	1166:1186	a significant decline in GLI activity	1166:1202	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	8	40	theme	proteins	1238:1245	arg1	expression					1208:1217	expression	1208:1217	expression of drug resistance proteins	1208:1245	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	5	41	theme	O-GlcNAc	781:788	arg1	transferase					790:800	inhibiting O-GlcNAc transferase	770:800	inhibiting O-GlcNAc transferase	770:800	The activity of GLI was enhanced when O-GlcNAcase was inhibited, while inhibiting O-GlcNAc transferase caused a decrease in GLI activity.
30420690	8	42	theme	PKM2	1143:1146	arg1	expression					1148:1157	PKM2 expression	1143:1157	PKM2 expression	1143:1157	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	6	43	theme	metabolic	841:849	arg1	impact					851:856	The metabolic impact	837:856	The metabolic impact of hyperglycemic conditions	837:884	The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways.
30420690	3	44	theme	pathway	548:554	arg1	factors					570:576	the Hedgehog pathway transcription factors	535:576	the Hedgehog pathway transcription factors	535:576	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	44	theme	pathway	548:554	arg1	GLI2					588:591	GLI2	588:591	GLI2	588:591	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	44	theme	pathway	548:554	arg1	GLI1					579:582	GLI1	579:582	GLI1	579:582	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	7	45	theme	elevated	1050:1057	arg1	conditions					1067:1076	elevated glucose conditions	1050:1076	elevated glucose conditions	1050:1076	Interestingly, under elevated glucose conditions, PKM2 directly influenced GLI activity.
30420690	1	46	theme	O-linked	129:136	arg1	O-GlcNAc					161:168	O-GlcNAc	161:168	O-GlcNAc	161:168	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	1	46	theme	O-linked	129:136	arg1	β-N-acetylglucosamine					138:158	O-linked β-N-acetylglucosamine	129:158	O-linked β-N-acetylglucosamine (O-GlcNAc)	129:169	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	0	47	theme	hyperglycemic	48:60	arg1	conditions					62:71	hyperglycemic conditions	48:71	hyperglycemic conditions	48:71	O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity.
30420690	9	48	theme	glucose	1296:1302	arg1	conditions					1304:1313	elevated glucose conditions	1287:1313	elevated glucose conditions	1287:1313	Cumulatively, our results suggest that elevated glucose conditions upregulate chemoresistance through elevated transcriptional activity of the Hedgehog/GLI pathway.
30420690	8	49	from	expression	1208:1217	arg1	activity					1195:1202	GLI activity	1191:1202	GLI activity	1191:1202	Specifically, abrogating PKM2 expression caused a significant decline in GLI activity and expression of drug resistance proteins.
30420690	3	50	theme	transcription	556:568	arg1	factors					570:576	the Hedgehog pathway transcription factors	535:576	the Hedgehog pathway transcription factors	535:576	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	50	theme	transcription	556:568	arg1	GLI2					588:591	GLI2	588:591	GLI2	588:591	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	3	50	theme	transcription	556:568	arg1	GLI1					579:582	GLI1	579:582	GLI1	579:582	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	2	51	theme	increased	345:353	arg1	expression					355:364	increased expression	345:364	increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway	345:481	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	6	52	theme	active	927:932	arg1	state					934:938	the less active state	918:938	the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways	918:1026	The metabolic impact of hyperglycemic conditions impinges on maintaining PKM2 in the less active state that facilitates the availability of glycolytic intermediates for biosynthetic pathways.
30420690	1	53	link	O-linked	129:136	arg1	O-GlcNAc					161:168	O-GlcNAc	161:168	O-GlcNAc	161:168	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	1	53	link	O-linked	129:136	arg1	β-N-acetylglucosamine					138:158	O-linked β-N-acetylglucosamine	129:158	O-linked β-N-acetylglucosamine (O-GlcNAc)	129:169	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	1	54	theme	proteins	117:124	arg1	Modification					101:112	Modification	101:112	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc)	101:169	Modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) promotes tumor cell survival, proliferation, epigenetic changes, angiogenesis, invasion, and metastasis.
30420690	7	55	theme	glucose	1059:1065	arg1	conditions					1067:1076	elevated glucose conditions	1050:1076	elevated glucose conditions	1050:1076	Interestingly, under elevated glucose conditions, PKM2 directly influenced GLI activity.
30420690	2	56	dep	proteins	389:396	arg1	ABCB1					399:403	ABCB1	399:403	ABCB1	399:403	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	56	dep	proteins	389:396	arg1	proteins					389:396	key drug resistance proteins	369:396	key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1)	369:429	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	56	dep	proteins	389:396	arg1	ERCC1					413:417	ERCC1	413:417	ERCC1	413:417	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	56	dep	proteins	389:396	arg1	XRCC1					424:428	XRCC1	424:428	XRCC1	424:428	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	56	dep	proteins	389:396	arg1	ABCG2					406:410	ABCG2	406:410	ABCG2	406:410	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	10	57	theme	transcription	1455:1467	arg1	factors					1469:1475	the GLI transcription factors	1447:1475	the GLI transcription factors	1447:1475	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	3	58	theme	elevated	487:494	arg1	conditions					504:513	elevated glucose conditions	487:513	elevated glucose conditions	487:513	In elevated glucose conditions, we determined that the Hedgehog pathway transcription factors, GLI1 and GLI2, are modified by O-GlcNAcylation.
30420690	2	59	theme	Hedgehog	466:473	arg1	pathway					475:481	the Hedgehog pathway	462:481	the Hedgehog pathway	462:481	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	10	60	theme	GLI	1451:1453	arg1	factors					1469:1475	the GLI transcription factors	1447:1475	the GLI transcription factors	1447:1475	Interfering in O-GlcNAcylation of the GLI transcription factors may be a novel target in controlling cancer progression and drug resistance of breast cancer.
30420690	5	61	theme	GLI	823:825	arg1	activity					827:834	GLI activity	823:834	GLI activity	823:834	The activity of GLI was enhanced when O-GlcNAcase was inhibited, while inhibiting O-GlcNAc transferase caused a decrease in GLI activity.
30420690	2	62	theme	resistance	378:387	arg1	ABCB1					399:403	ABCB1	399:403	ABCB1	399:403	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	62	theme	resistance	378:387	arg1	proteins					389:396	key drug resistance proteins	369:396	key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1)	369:429	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	62	theme	resistance	378:387	arg1	ERCC1					413:417	ERCC1	413:417	ERCC1	413:417	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	62	theme	resistance	378:387	arg1	XRCC1					424:428	XRCC1	424:428	XRCC1	424:428	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	62	theme	resistance	378:387	arg1	ABCG2					406:410	ABCG2	406:410	ABCG2	406:410	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	0	63	theme	GLI	19:21	arg1	factors					37:43	GLI transcription factors	19:43	GLI transcription factors	19:43	O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity.
30420690	2	64	theme	drug	373:376	arg1	ABCB1					399:403	ABCB1	399:403	ABCB1	399:403	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	64	theme	drug	373:376	arg1	proteins					389:396	key drug resistance proteins	369:396	key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1)	369:429	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	64	theme	drug	373:376	arg1	ERCC1					413:417	ERCC1	413:417	ERCC1	413:417	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	64	theme	drug	373:376	arg1	XRCC1					424:428	XRCC1	424:428	XRCC1	424:428	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30420690	2	64	theme	drug	373:376	arg1	ABCG2					406:410	ABCG2	406:410	ABCG2	406:410	Here we demonstrate that in conditions of elevated glucose, there is increased expression of key drug resistance proteins (ABCB1, ABCG2, ERCC1, and XRCC1), all of which are regulated by the Hedgehog pathway.
30327117	0	0	theme	O-GlcNAc	85:92	arg1	quantification					67:80	the accurate and sensitive quantification	40:80	the accurate and sensitive quantification of O-GlcNAc	40:92	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc based on cleavage by β-D-N-acetylglucosaminidase.
30327117	7	1	theme	O-GlcNAc	1332:1339	arg1	detection					1319:1327	the accurate detection	1306:1327	the accurate detection of O-GlcNAc	1306:1339	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	10	2	theme	O-GlcNAc-related	1861:1876	arg1	diseases					1878:1885	O-GlcNAc-related diseases	1861:1885	O-GlcNAc-related diseases	1861:1885	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	3	3	theme	accurate	486:493	arg1	biosensor					541:549	an accurate and sensitive surface plasmon resonance (SPR) biosensor	483:549	an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs)	483:652	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	8	4	theme	accurate	1346:1353	arg1	range					1365:1369	The accurate detection range	1342:1369	The accurate detection range of O-GlcNAc	1342:1381	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	4	theme	accurate	1346:1353	arg1	4.65 × 10-7 M					1403:1415	4.65 × 10-7 M	1403:1415	4.65 × 10-7 M	1403:1415	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	5	5	theme	germ	880:883	arg1	AuNPs/WGA					897:905	AuNPs/WGA	897:905	AuNPs/WGA	897:905	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	5	5	theme	germ	880:883	arg1	agglutinin					885:894	AuNPs labeled wheat germ agglutinin	860:894	AuNPs labeled wheat germ agglutinin (AuNPs/WGA)	860:906	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	4	6	from	biomolecules	822:833	arg1	O-GlcNAc					793:800	O-GlcNAc	793:800	O-GlcNAc from O-GlcNAcylated biomolecules	793:833	In this strategy, AuNPs were used to amplify the SPR signal and improve the biosensor's sensitivity; OGA was used to cleave O-GlcNAc from O-GlcNAcylated biomolecules.
30327117	4	7	theme	O-GlcNAcylated	807:820	arg1	biomolecules					822:833	O-GlcNAcylated biomolecules	807:833	O-GlcNAcylated biomolecules	807:833	In this strategy, AuNPs were used to amplify the SPR signal and improve the biosensor's sensitivity; OGA was used to cleave O-GlcNAc from O-GlcNAcylated biomolecules.
30327117	5	8	theme	AuNPs	860:864	arg1	AuNPs/WGA					897:905	AuNPs/WGA	897:905	AuNPs/WGA	897:905	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	5	8	theme	AuNPs	860:864	arg1	agglutinin					885:894	AuNPs labeled wheat germ agglutinin	860:894	AuNPs labeled wheat germ agglutinin (AuNPs/WGA)	860:906	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	5	9	theme	labeled	866:872	arg1	AuNPs/WGA					897:905	AuNPs/WGA	897:905	AuNPs/WGA	897:905	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	5	9	theme	labeled	866:872	arg1	agglutinin					885:894	AuNPs labeled wheat germ agglutinin	860:894	AuNPs labeled wheat germ agglutinin (AuNPs/WGA)	860:906	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	4	10	used	used	698:701	arg2	AuNPs					687:691	AuNPs	687:691	AuNPs	687:691	In this strategy, AuNPs were used to amplify the SPR signal and improve the biosensor's sensitivity; OGA was used to cleave O-GlcNAc from O-GlcNAcylated biomolecules.
30327117	8	11	theme	detection	1355:1363	arg1	range					1365:1369	The accurate detection range	1342:1369	The accurate detection range of O-GlcNAc	1342:1381	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	11	theme	detection	1355:1363	arg1	4.65 × 10-7 M					1403:1415	4.65 × 10-7 M	1403:1415	4.65 × 10-7 M	1403:1415	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	6	12	theme	signal	1034:1039	arg1	change					1016:1021	The change	1012:1021	The change of the SPR signal	1012:1039	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	2	13	dep	complicated	354:364	arg1	time-consuming					367:380	time-consuming	367:380	time-consuming	367:380	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	6	14	theme	O-GlcNAc	1075:1082	arg1	O-GlcNAc					1075:1082	O-GlcNAc	1075:1082	O-GlcNAc	1075:1082	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	6	14	theme	O-GlcNAc	1075:1082	arg1	amount					1065:1070	the amount	1061:1070	the amount of O-GlcNAc on the Au film	1061:1097	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	7	15	theme	accurate	1310:1317	arg1	detection					1319:1327	the accurate detection	1306:1327	the accurate detection of O-GlcNAc	1306:1339	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	10	16	theme	clinical	1839:1846	arg1	diagnosis					1848:1856	the early clinical diagnosis	1829:1856	the early clinical diagnosis of O-GlcNAc-related diseases	1829:1885	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	5	17	from	interaction	840:850	arg1	film					957:960	a modified Au film	943:960	a modified Au film treated with and without OGA	943:989	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	4	18	theme	SPR	718:720	arg1	signal					722:727	the SPR signal	714:727	the SPR signal	714:727	In this strategy, AuNPs were used to amplify the SPR signal and improve the biosensor's sensitivity; OGA was used to cleave O-GlcNAc from O-GlcNAcylated biomolecules.
30327117	7	19	from	sugars	1247:1252	arg1	disturbances					1223:1234	disturbances	1223:1234	disturbances from other sugars	1223:1252	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	7	19	from	sugars	1247:1252	arg1	adsorption					1270:1279	nonspecific adsorption	1258:1279	nonspecific adsorption of AuNPs	1258:1288	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	8	20	dep	4.65 × 10-7 M	1403:1415	arg1	to					1400:1401	to	1400:1401	to	1400:1401	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	7	21	theme	SPR	1188:1190	arg1	signals					1192:1198	the SPR signals	1184:1198	the SPR signals	1184:1198	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	3	22	theme	plasmon	517:523	arg1	SPR					536:538	SPR	536:538	SPR	536:538	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	3	22	theme	plasmon	517:523	arg1	resonance					525:533	surface plasmon resonance	509:533	an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs)	483:652	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	4	23	used	used	778:781	arg2	OGA					770:772	OGA	770:772	OGA	770:772	In this strategy, AuNPs were used to amplify the SPR signal and improve the biosensor's sensitivity; OGA was used to cleave O-GlcNAc from O-GlcNAcylated biomolecules.
30327117	9	24	with	protein	1654:1660	arg1	results					1719:1725	satisfactory results	1706:1725	satisfactory results	1706:1725	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	3	25	theme	resonance	525:533	arg1	biosensor					541:549	an accurate and sensitive surface plasmon resonance (SPR) biosensor	483:549	an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs)	483:652	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	6	26	theme	SPR	1030:1032	arg1	signal					1034:1039	the SPR signal	1026:1039	the SPR signal	1026:1039	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	2	27	theme	poor	390:393	arg1	specificity					395:405	poor specificity	390:405	poor specificity	390:405	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	0	28	theme	plasmon	8:14	arg1	resonance					16:24	Surface plasmon resonance	0:24	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc	0:92	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc based on cleavage by β-D-N-acetylglucosaminidase.
30327117	8	29	theme	standard	1467:1474	arg1	O-GlcNAc-CREB					1500:1512	O-GlcNAc-CREB	1500:1512	O-GlcNAc-CREB	1500:1512	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	29	theme	standard	1467:1474	arg1	peptide					1491:1497	a standard O-GlcNAcylated peptide	1465:1497	a standard O-GlcNAcylated peptide (O-GlcNAc-CREB)	1465:1513	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	10	30	theme	diseases	1878:1885	arg1	diagnosis					1848:1856	the early clinical diagnosis	1829:1856	the early clinical diagnosis of O-GlcNAc-related diseases	1829:1885	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	6	31	theme	Au	1091:1092	arg1	film					1094:1097	the Au film	1087:1097	the Au film	1087:1097	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	10	32	theme	early	1833:1837	arg1	diagnosis					1848:1856	the early clinical diagnosis	1829:1856	the early clinical diagnosis of O-GlcNAc-related diseases	1829:1885	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	0	33	theme	Surface	0:6	arg1	resonance					16:24	Surface plasmon resonance	0:24	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc	0:92	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc based on cleavage by β-D-N-acetylglucosaminidase.
30327117	10	34	contain	has	1794:1796	arg1	method					1787:1792	this accurate and sensitive method	1759:1792	this accurate and sensitive method	1759:1792	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	10	34	contain	has	1794:1796	arg2	potential					1802:1810	the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases	1798:1885	the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases	1798:1885	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	3	35	theme	O-GlcNAc	555:562	arg1	detection					564:572	O-GlcNAc detection	555:572	O-GlcNAc detection	555:572	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	2	36	contain	has	386:388	arg1	detection					341:349	O-GlcNAc detection	332:349	O-GlcNAc detection	332:349	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	2	36	contain	has	386:388	arg2	specificity					395:405	poor specificity	390:405	poor specificity	390:405	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	1	37	theme	cardiovascular	292:305	arg1	disease					307:313	cardiovascular disease	292:313	cardiovascular disease	292:313	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	1	37	theme	cardiovascular	292:305	arg1	cancer					263:268	cancer	263:268	cancer	263:268	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	9	38	with	samples	1693:1699	arg1	results					1719:1725	satisfactory results	1706:1725	satisfactory results	1706:1725	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	2	39	theme	accurate	423:430	arg1	difficult					457:465	difficult	457:465	difficult	457:465	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	2	39	theme	accurate	423:430	arg1	detection					432:440	the accurate detection	419:440	the accurate detection of O-GlcNAc	419:452	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	8	40	theme	O-GlcNAcylated	1476:1489	arg1	O-GlcNAc-CREB					1500:1512	O-GlcNAc-CREB	1500:1512	O-GlcNAc-CREB	1500:1512	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	40	theme	O-GlcNAcylated	1476:1489	arg1	peptide					1491:1497	a standard O-GlcNAcylated peptide	1465:1497	a standard O-GlcNAcylated peptide (O-GlcNAc-CREB)	1465:1513	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	3	41	theme	Au	629:630	arg1	AuNPs					647:651	AuNPs	647:651	AuNPs	647:651	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	3	41	theme	Au	629:630	arg1	nanoparticles					632:644	Au nanoparticles	629:644	Au nanoparticles (AuNPs)	629:652	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	5	42	theme	O-GlcNAcylated	912:925	arg1	biomolecules					927:938	O-GlcNAcylated biomolecules	912:938	O-GlcNAcylated biomolecules	912:938	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	2	43	theme	O-GlcNAc	445:452	arg1	difficult					457:465	difficult	457:465	difficult	457:465	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	2	43	theme	O-GlcNAc	445:452	arg1	detection					432:440	the accurate detection	419:440	the accurate detection of O-GlcNAc	419:452	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	1	44	dep	cancer	263:268	arg1	e.g.					257:260	e.g.	257:260	e.g.	257:260	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	7	45	dep	avoid	1217:1221	arg1	enable					1299:1304	enable	1299:1304	enable the accurate detection of O-GlcNAc	1299:1339	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	6	46	theme	O-GlcNAc	1143:1150	arg1	detection					1130:1138	the detection	1126:1138	the detection of O-GlcNAc	1126:1150	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	1	47	theme	diseases	247:254	arg1	variety					236:242	a variety	234:242	a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.)	234:320	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	1	47	theme	diseases	247:254	arg1	diseases					247:254	diseases	247:254	diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.)	247:320	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	8	48	theme	peptide	1491:1497	arg1	O-GlcNAc-CREB					1500:1512	O-GlcNAc-CREB	1500:1512	O-GlcNAc-CREB	1500:1512	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	48	theme	peptide	1491:1497	arg1	peptide					1491:1497	a standard O-GlcNAcylated peptide	1465:1497	a standard O-GlcNAcylated peptide (O-GlcNAc-CREB)	1465:1513	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	48	theme	peptide	1491:1497	arg1	amount					1455:1460	the amount	1451:1460	the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB)	1451:1513	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	10	49	theme	accurate	1764:1771	arg1	method					1787:1792	this accurate and sensitive method	1759:1792	this accurate and sensitive method	1759:1792	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	9	50	theme	cancer	1663:1668	arg1	lysates					1675:1681	cancer cell lysates	1663:1681	cancer cell lysates	1663:1681	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	9	51	theme	α-crystallin	1641:1652	arg1	protein					1654:1660	a real α-crystallin protein	1634:1660	a real α-crystallin protein	1634:1660	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	5	52	theme	wheat	874:878	arg1	AuNPs/WGA					897:905	AuNPs/WGA	897:905	AuNPs/WGA	897:905	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	5	52	theme	wheat	874:878	arg1	agglutinin					885:894	AuNPs labeled wheat germ agglutinin	860:894	AuNPs labeled wheat germ agglutinin (AuNPs/WGA)	860:906	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	0	53	theme	accurate	44:51	arg1	quantification					67:80	the accurate and sensitive quantification	40:80	the accurate and sensitive quantification of O-GlcNAc	40:92	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc based on cleavage by β-D-N-acetylglucosaminidase.
30327117	9	54	theme	real	1636:1639	arg1	protein					1654:1660	a real α-crystallin protein	1634:1660	a real α-crystallin protein	1634:1660	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	7	55	theme	AuNPs	1284:1288	arg1	disturbances					1223:1234	disturbances	1223:1234	disturbances from other sugars	1223:1252	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	7	55	theme	AuNPs	1284:1288	arg1	adsorption					1270:1279	nonspecific adsorption	1258:1279	nonspecific adsorption of AuNPs	1258:1288	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	2	56	theme	O-GlcNAc	332:339	arg1	detection					341:349	O-GlcNAc detection	332:349	O-GlcNAc detection	332:349	However, O-GlcNAc detection is complicated, time-consuming and has poor specificity, therefore, the accurate detection of O-GlcNAc is difficult.
30327117	8	57	theme	O-GlcNAc	1374:1381	arg1	range					1365:1369	The accurate detection range	1342:1369	The accurate detection range of O-GlcNAc	1342:1381	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	57	theme	O-GlcNAc	1374:1381	arg1	4.65 × 10-7 M					1403:1415	4.65 × 10-7 M	1403:1415	4.65 × 10-7 M	1403:1415	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	7	58	theme	nonspecific	1258:1268	arg1	adsorption					1270:1279	nonspecific adsorption	1258:1279	nonspecific adsorption of AuNPs	1258:1288	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	5	59	theme	Au	954:955	arg1	film					957:960	a modified Au film	943:960	a modified Au film treated with and without OGA	943:989	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	6	60	from	amount	1065:1070	arg1	film					1094:1097	the Au film	1087:1097	the Au film	1087:1097	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	1	61	theme	Abnormal	144:151	arg1	O-GlcNAc					183:190	O-GlcNAc	183:190	O-GlcNAc	183:190	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	1	61	theme	Abnormal	144:151	arg1	O-linked-N-acetylglucosamine					153:180	Abnormal O-linked-N-acetylglucosamine	144:180	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations	144:206	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	6	62	used	used	1117:1120	arg2	change					1016:1021	The change	1012:1021	The change of the SPR signal	1012:1039	The change of the SPR signal moves linearly with the amount of O-GlcNAc on the Au film and thus could be used for the detection of O-GlcNAc.
30327117	9	63	theme	cell	1670:1673	arg1	lysates					1675:1681	cancer cell lysates	1663:1681	cancer cell lysates	1663:1681	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	5	64	theme	modified	945:952	arg1	film					957:960	a modified Au film	943:960	a modified Au film treated with and without OGA	943:989	The interaction between AuNPs labeled wheat germ agglutinin (AuNPs/WGA) and O-GlcNAcylated biomolecules on a modified Au film treated with and without OGA was recorded by SPR.
30327117	7	65	theme	signals	1192:1198	arg1	difference					1170:1179	the difference	1166:1179	the difference of the SPR signals	1166:1198	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	9	66	with	lysates	1675:1681	arg1	results					1719:1725	satisfactory results	1706:1725	satisfactory results	1706:1725	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	1	67	theme	O-linked-N-acetylglucosamine	153:180	arg1	concentrations					193:206	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations	144:206	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations	144:206	Abnormal O-linked-N-acetylglucosamine (O-GlcNAc) concentrations have been associated with a variety of diseases (e.g., cancer, Alzheimer's disease, cardiovascular disease, etc.).
30327117	9	68	theme	satisfactory	1706:1717	arg1	results					1719:1725	satisfactory results	1706:1725	satisfactory results	1706:1725	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	10	69	theme	sensitive	1777:1785	arg1	method					1787:1792	this accurate and sensitive method	1759:1792	this accurate and sensitive method	1759:1792	The study's results imply that this accurate and sensitive method has the potential to be applied in the early clinical diagnosis of O-GlcNAc-related diseases.
30327117	3	70	theme	sensitive	499:507	arg1	biosensor					541:549	an accurate and sensitive surface plasmon resonance (SPR) biosensor	483:549	an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs)	483:652	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	7	71	theme	other	1241:1245	arg1	sugars					1247:1252	other sugars	1241:1252	other sugars	1241:1252	By recording the difference of the SPR signals, this method can avoid disturbances from other sugars and nonspecific adsorption of AuNPs and thus enable the accurate detection of O-GlcNAc.
30327117	8	72	theme	detection	1524:1532	arg1	4.65 × 10-13 M					1543:1556	4.65 × 10-13 M	1543:1556	4.65 × 10-13 M	1543:1556	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	8	72	theme	detection	1524:1532	arg1	limit					1534:1538	the detection limit	1520:1538	the detection limit	1520:1538	The accurate detection range of O-GlcNAc was 4.65 × 10-12 to 4.65 × 10-7 M which was obtained by quantifying the amount of a standard O-GlcNAcylated peptide (O-GlcNAc-CREB), and the detection limit is 4.65 × 10-13 M.
30327117	0	73	theme	sensitive	57:65	arg1	quantification					67:80	the accurate and sensitive quantification	40:80	the accurate and sensitive quantification of O-GlcNAc	40:92	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc based on cleavage by β-D-N-acetylglucosaminidase.
30327117	9	74	used	used	1607:1610	arg2	strategy					1581:1588	the strategy	1577:1588	the strategy	1577:1588	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30327117	0	75	theme	resonance	16:24	arg1	biosensor					26:34	Surface plasmon resonance biosensor	0:34	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc	0:92	Surface plasmon resonance biosensor for the accurate and sensitive quantification of O-GlcNAc based on cleavage by β-D-N-acetylglucosaminidase.
30327117	3	76	theme	surface	509:515	arg1	SPR					536:538	SPR	536:538	SPR	536:538	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	3	76	theme	surface	509:515	arg1	resonance					525:533	surface plasmon resonance	509:533	an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs)	483:652	In this study, an accurate and sensitive surface plasmon resonance (SPR) biosensor for O-GlcNAc detection that is based on β-D-N-acetylglucosaminidase (OGA) and Au nanoparticles (AuNPs) was developed.
30327117	9	77	theme	blood	1687:1691	arg1	samples					1693:1699	blood samples	1687:1699	blood samples	1687:1699	More importantly, the strategy was successfully used to detect O-GlcNAc in a real α-crystallin protein, cancer cell lysates and blood samples with satisfactory results.
30712865	4	0	theme	conformational	813:826	arg1	changes					828:834	fusogenic conformational changes	803:834	fusogenic conformational changes	803:834	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
30712865	3	1	attach	isolated	646:653	arg1	survivors					666:674	human survivors	660:674	human survivors	660:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	3	1	attach	isolated	646:653	arg2	antibodies					635:644	neutralizing antibodies	622:644	neutralizing antibodies isolated from human survivors	622:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	2	2	theme	into host	371:379	arg1	cells					381:385	entry into host cells	365:385	entry into host cells	365:385	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	5	3	theme	ratcheting	1084:1093	arg1	mechanism					1095:1103	a receptor-driven ratcheting mechanism	1066:1103	a receptor-driven ratcheting mechanism	1066:1103	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	3	4	theme	MERS-CoV	581:588	arg1	glycoproteins					592:604	the SARS-CoV and MERS-CoV S glycoproteins	564:604	the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors	564:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	4	5	theme	fusogenic	803:811	arg1	changes					828:834	fusogenic conformational changes	803:834	fusogenic conformational changes	803:834	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
30712865	3	6	theme	S	590:590	arg1	glycoproteins					592:604	the SARS-CoV and MERS-CoV S glycoproteins	564:604	the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors	564:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	3	7	gly	glycoproteins	592:604	arg1	glycoproteins					592:604	the SARS-CoV and MERS-CoV S glycoproteins	564:604	the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors	564:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	5	8	theme	coronavirus	932:942	arg1	neutralization					944:957	coronavirus neutralization	932:957	coronavirus neutralization by human antibodies	932:977	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	2	9	theme	entry	365:369	arg1	cells					381:385	entry into host cells	365:385	entry into host cells	365:385	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	3	10	with	infections	503:512	arg1	coronaviruses					519:531	coronaviruses	519:531	coronaviruses	519:531	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	3	11	theme	natural	495:501	arg1	infections					503:512	natural infections	495:512	natural infections with coronaviruses	495:531	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	1	12	theme	Recent	84:89	arg1	outbreaks					91:99	Recent outbreaks	84:99	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome	84:173	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	3	13	theme	humoral	457:463	arg1	response					472:479	the humoral immune response	453:479	the humoral immune response elicited upon natural infections with coronaviruses	453:531	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	4	14	theme	receptor	840:847	arg1	mimicry					860:866	receptor functional mimicry	840:866	receptor functional mimicry	840:866	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
30712865	3	15	theme	immune	465:470	arg1	response					472:479	the humoral immune response	453:479	the humoral immune response elicited upon natural infections with coronaviruses	453:531	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	0	16	theme	Receptor	11:18	arg1	Mimicry					31:37	Unexpected Receptor Functional Mimicry	0:37	Unexpected Receptor Functional Mimicry	0:37	Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
30712865	2	17	theme	spike	321:325	arg1	glycoprotein					341:352	The trimeric spike transmembrane glycoprotein	308:352	The trimeric spike transmembrane glycoprotein S	308:354	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	2	18	theme	transmembrane	327:339	arg1	glycoprotein					341:352	The trimeric spike transmembrane glycoprotein	308:352	The trimeric spike transmembrane glycoprotein S	308:354	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	3	19	theme	SARS-CoV	568:575	arg1	glycoproteins					592:604	the SARS-CoV and MERS-CoV S glycoproteins	564:604	the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors	564:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	2	20	theme	major	398:402	arg1	target					404:409	the major target	394:409	the major target of neutralizing antibodies	394:436	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	0	21	theme	Unexpected	0:9	arg1	Mimicry					31:37	Unexpected Receptor Functional Mimicry	0:37	Unexpected Receptor Functional Mimicry	0:37	Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
30712865	4	22	theme	anti-SARS-CoV	768:780	arg1	antibody					784:791	only the anti-SARS-CoV S antibody	759:791	only the anti-SARS-CoV S antibody	759:791	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
30712865	1	23	theme	severe	104:109	arg1	syndrome					129:136	severe acute respiratory syndrome	104:136	severe acute respiratory syndrome	104:136	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	3	24	with	complex	609:615	arg1	antibodies					635:644	neutralizing antibodies	622:644	neutralizing antibodies isolated from human survivors	622:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	5	25	theme	fusion	1032:1037	arg1	activation					997:1006	activation	997:1006	activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism	997:1103	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	1	26	theme	acute	111:115	arg1	syndrome					129:136	severe acute respiratory syndrome	104:136	severe acute respiratory syndrome	104:136	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	0	27	theme	Functional	20:29	arg1	Mimicry					31:37	Unexpected Receptor Functional Mimicry	0:37	Unexpected Receptor Functional Mimicry	0:37	Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
30712865	1	28	dep	syndrome	129:136	arg1	syndrome					166:173	respiratory syndrome	154:173	respiratory syndrome	154:173	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	1	29	theme	respiratory	117:127	arg1	syndrome					129:136	severe acute respiratory syndrome	104:136	severe acute respiratory syndrome	104:136	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	1	30	theme	future	203:208	arg1	pandemic					231:238	a future coronavirus-mediated pandemic	201:238	a future coronavirus-mediated pandemic	201:238	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	1	31	theme	coronavirus-mediated	210:229	arg1	pandemic					231:238	a future coronavirus-mediated pandemic	201:238	a future coronavirus-mediated pandemic	201:238	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	2	32	theme	antibodies	427:436	arg1	target					404:409	the major target	394:409	the major target of neutralizing antibodies	394:436	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	4	33	theme	cell	744:747	arg1	receptor					749:756	the host cell receptor	735:756	the host cell receptor	735:756	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
30712865	5	34	theme	structural	893:902	arg1	framework					904:912	a structural framework	891:912	a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism	891:1103	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	1	35	theme	pandemic	231:238	arg1	threat					191:196	the threat	187:196	the threat of a future coronavirus-mediated pandemic	187:238	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	0	36	theme	Coronavirus	64:74	arg1	Fusion					76:81	Coronavirus Fusion	64:81	Coronavirus Fusion	64:81	Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
30712865	3	37	theme	neutralizing	622:633	arg1	antibodies					635:644	neutralizing antibodies	622:644	neutralizing antibodies isolated from human survivors	622:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	1	38	theme	syndrome	129:136	arg1	outbreaks					91:99	Recent outbreaks	84:99	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome	84:173	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	5	39	theme	coronavirus	1011:1021	arg1	fusion					1032:1037	coronavirus membrane fusion	1011:1037	coronavirus membrane fusion	1011:1037	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	3	40	from	glycoproteins	592:604	arg1	complex					609:615	complex	609:615	complex with neutralizing antibodies isolated from human survivors	609:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	2	41	gly	glycoprotein	341:352	arg1	glycoprotein					341:352	The trimeric spike transmembrane glycoprotein	308:352	The trimeric spike transmembrane glycoprotein S	308:354	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	4	42	theme	S	782:782	arg1	antibody					784:791	only the anti-SARS-CoV S antibody	759:791	only the anti-SARS-CoV S antibody	759:791	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
30712865	2	43	theme	trimeric	312:319	arg1	glycoprotein					341:352	The trimeric spike transmembrane glycoprotein	308:352	The trimeric spike transmembrane glycoprotein S	308:354	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	4	44	theme	functional	849:858	arg1	mimicry					860:866	receptor functional mimicry	840:866	receptor functional mimicry	840:866	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
30712865	5	45	theme	receptor-driven	1068:1082	arg1	mechanism					1095:1103	a receptor-driven ratcheting mechanism	1066:1103	a receptor-driven ratcheting mechanism	1066:1103	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	1	46	theme	East	149:152	arg1	outbreaks					91:99	Recent outbreaks	84:99	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome	84:173	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	5	47	theme	membrane	1023:1030	arg1	fusion					1032:1037	coronavirus membrane fusion	1011:1037	coronavirus membrane fusion	1011:1037	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	2	48	theme	neutralizing	414:425	arg1	antibodies					427:436	neutralizing antibodies	414:436	neutralizing antibodies	414:436	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	3	49	theme	human	660:664	arg1	survivors					666:674	human survivors	660:674	human survivors	660:674	To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors.
30712865	1	50	theme	respiratory	154:164	arg1	syndrome					166:173	respiratory syndrome	154:173	respiratory syndrome	154:173	Recent outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, along with the threat of a future coronavirus-mediated pandemic, underscore the importance of finding ways to combat these viruses.
30712865	5	51	theme	human	962:966	arg1	antibodies					968:977	human antibodies	962:977	human antibodies	962:977	These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.
30712865	0	52	theme	Fusion	76:81	arg1	Activation					50:59	Activation	50:59	Activation of Coronavirus Fusion	50:81	Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
30712865	2	53	dep	glycoprotein	341:352	arg1	S					354:354	S	354:354	The trimeric spike transmembrane glycoprotein S	308:354	The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies.
30712865	4	54	theme	host	739:742	arg1	receptor					749:756	the host cell receptor	735:756	the host cell receptor	735:756	Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry.
31337705	5	0	theme	sperm	615:619	arg1	percentage					594:603	the highest percentage	582:603	the highest percentage of bovine sperm	582:619	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	7	1	theme	MS	937:938	arg1	analyses					965:972	MS and immunohistochemistry analyses	937:972	MS and immunohistochemistry analyses	937:972	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	2	2	theme	sperm	343:347	arg1	population					329:338	a fertile population	319:338	a fertile population of sperm	319:347	This reservoir delays capacitation, prevents polyspermy, selects a fertile population of sperm, and, foremost, increases sperm lifespan.
31337705	5	3	theme	fluoresceinated	718:732	arg1	versions					734:741	fluoresceinated versions	718:741	fluoresceinated versions of each	718:749	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	4	4	theme	Sperm	497:501	arg1	lectins					503:509	Sperm lectins	497:509	Sperm lectins	497:509	Sperm lectins bind to oviductal glycans to form the reservoir.
31337705	7	5	theme	Lewis	1097:1101	arg1	A					1103:1103	no sialylated Lewis A	1083:1103	no sialylated Lewis A	1083:1103	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	10	6	theme	reservoir	1736:1744	arg1	formation					1746:1754	reservoir formation	1736:1754	reservoir formation	1736:1754	These results indicate that bovine sperm binding to oviduct suLeA retains sperm for reservoir formation and extends sperm lifespan.
31337705	7	7	theme	sialylated	1086:1095	arg1	A					1103:1103	no sialylated Lewis A	1083:1103	no sialylated Lewis A	1083:1103	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	0	8	theme	sperm	98:102	arg1	lifespan					104:111	sperm lifespan	98:111	sperm lifespan	98:111	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	9	9	theme	sperm	1564:1568	arg1	viability					1551:1559	viability	1551:1559	viability of sperm bound to immobilized suLeA	1551:1595	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	9	10	theme	immobilized	1499:1509	arg1	laminin					1511:1517	immobilized laminin	1499:1517	immobilized laminin	1499:1517	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	8	11	theme	sperm	1244:1248	arg1	longevity					1250:1258	sperm longevity	1244:1258	sperm longevity	1244:1258	To determine whether sperm binding to isolated suLeAin vitro could mimic in vivo sperm binding to oviduct cells and increase sperm longevity, we immobilized suLeA and incubated it with sperm.
31337705	9	12	theme	free-swimming	1317:1329	arg1	controls					1379:1386	controls	1379:1386	controls	1379:1386	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	9	12	theme	free-swimming	1317:1329	arg1	sperm					1341:1345	sperm	1341:1345	sperm	1341:1345	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	9	12	theme	free-swimming	1317:1329	arg1	sperm					1331:1335	free-swimming sperm	1317:1335	free-swimming sperm	1317:1335	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	9	13	theme	sperm	1448:1452	arg1	viability					1421:1429	the viability	1417:1429	the viability of free-swimming sperm	1417:1452	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	5	14	theme	sialylated	690:699	arg1	A					707:707	sialylated Lewis A	690:707	sialylated Lewis A	690:707	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	5	15	theme	highest	586:592	arg1	percentage					594:603	the highest percentage	582:603	the highest percentage of bovine sperm	582:619	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	7	16	gly	sialylated	1086:1095	arg1	A					1103:1103	no sialylated Lewis A	1083:1103	no sialylated Lewis A	1083:1103	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	7	17	attach	present	1007:1013	arg2	motifs					995:1000	suLeA motifs	989:1000	suLeA motifs	989:1000	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	7	17	attach	present	1007:1013	arg1	glycans					1041:1047	O-linked glycans	1032:1047	O-linked glycans initiated by GalNAc residues	1032:1076	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	5	18	theme	sperm	802:806	arg1	head					790:793	the anterior head	777:793	the anterior head of the sperm	777:806	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	5	19	theme	Lewis	701:705	arg1	A					707:707	sialylated Lewis A	690:707	sialylated Lewis A	690:707	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	9	20	theme	immobilized	1579:1589	arg1	suLeA					1591:1595	immobilized suLeA	1579:1595	immobilized suLeA	1579:1595	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	8	21	theme	sperm	1140:1144	arg1	binding					1146:1152	sperm binding	1140:1152	sperm binding to isolated suLeAin vitro	1140:1178	To determine whether sperm binding to isolated suLeAin vitro could mimic in vivo sperm binding to oviduct cells and increase sperm longevity, we immobilized suLeA and incubated it with sperm.
31337705	0	22	theme	Lewis	9:13	arg1	A					15:15	Sulfated Lewis A	0:15	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins	0:63	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	5	23	from	receptors	764:772	arg1	head					790:793	the anterior head	777:793	the anterior head of the sperm	777:806	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	5	24	theme	A	707:707	arg1	form					648:651	the 3'-O-sulfated form	630:651	the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A	630:707	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	10	25	theme	bovine	1680:1685	arg1	sperm					1687:1691	bovine sperm	1680:1691	bovine sperm binding to oviduct suLeA	1680:1716	These results indicate that bovine sperm binding to oviduct suLeA retains sperm for reservoir formation and extends sperm lifespan.
31337705	3	26	theme	molecular	395:403	arg1	interactions					405:416	The molecular interactions	391:416	The molecular interactions underlying the formation of a sperm reservoir	391:462	The molecular interactions underlying the formation of a sperm reservoir are becoming clearer in mammals.
31337705	0	27	theme	Sulfated	0:7	arg1	A					15:15	Sulfated Lewis A	0:15	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins	0:63	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	5	28	theme	bovine	608:613	arg1	sperm					615:619	bovine sperm	608:619	bovine sperm	608:619	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	8	29	theme	oviduct	1217:1223	arg1	cells					1225:1229	oviduct cells	1217:1229	oviduct cells	1217:1229	To determine whether sperm binding to isolated suLeAin vitro could mimic in vivo sperm binding to oviduct cells and increase sperm longevity, we immobilized suLeA and incubated it with sperm.
31337705	1	30	theme	oviduct	182:188	arg1	isthmus					190:196	the oviduct isthmus	178:196	the oviduct isthmus	178:196	A fraction of sperm deposited at mating or insemination reaches the oviduct isthmus, where sperm are retained and thereby form a reservoir.
31337705	5	31	theme	A	662:662	arg1	trisaccharide					672:684	Lewis A (suLeA) trisaccharide	656:684	Lewis A (suLeA) trisaccharide	656:684	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	5	32	theme	anterior	781:788	arg1	head					790:793	the anterior head	777:793	the anterior head of the sperm	777:806	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	0	33	theme	A	15:15	arg1	trisaccharide					17:29	Sulfated Lewis A trisaccharide	0:29	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins	0:63	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	9	34	theme	free-swimming	1434:1446	arg1	sperm					1448:1452	free-swimming sperm	1434:1452	free-swimming sperm	1434:1452	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	5	35	gly	sialylated	690:699	arg1	A					707:707	sialylated Lewis A	690:707	sialylated Lewis A	690:707	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	3	36	theme	sperm	448:452	arg1	reservoir					454:462	a sperm reservoir	446:462	a sperm reservoir	446:462	The molecular interactions underlying the formation of a sperm reservoir are becoming clearer in mammals.
31337705	0	37	theme	oviduct	34:40	arg1	glycoproteins					51:63	oviduct membrane glycoproteins	34:63	oviduct membrane glycoproteins	34:63	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	7	38	located	present	1007:1013	arg2	motifs					995:1000	suLeA motifs	989:1000	suLeA motifs	989:1000	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	7	38	located	present	1007:1013	arg1	glycans					1041:1047	O-linked glycans	1032:1047	O-linked glycans initiated by GalNAc residues	1032:1076	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	6	39	from	reservoir	926:934	arg1	release					909:915	sperm release	903:915	sperm release from the reservoir	903:934	Following capacitation, binding to suLeA decreased significantly, a potential explanation for sperm release from the reservoir.
31337705	10	40	theme	oviduct	1704:1710	arg1	suLeA					1712:1716	oviduct suLeA	1704:1716	oviduct suLeA	1704:1716	These results indicate that bovine sperm binding to oviduct suLeA retains sperm for reservoir formation and extends sperm lifespan.
31337705	8	41	theme	sperm	1200:1204	arg1	binding					1206:1212	in vivo sperm binding	1192:1212	in vivo sperm binding to oviduct cells	1192:1229	To determine whether sperm binding to isolated suLeAin vitro could mimic in vivo sperm binding to oviduct cells and increase sperm longevity, we immobilized suLeA and incubated it with sperm.
31337705	6	42	theme	sperm	903:907	arg1	release					909:915	sperm release	903:915	sperm release from the reservoir	903:934	Following capacitation, binding to suLeA decreased significantly, a potential explanation for sperm release from the reservoir.
31337705	7	43	theme	O-linked	1032:1039	arg1	glycans					1041:1047	O-linked glycans	1032:1047	O-linked glycans initiated by GalNAc residues	1032:1076	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	2	44	theme	sperm	375:379	arg1	lifespan					381:388	sperm lifespan	375:388	sperm lifespan	375:388	This reservoir delays capacitation, prevents polyspermy, selects a fertile population of sperm, and, foremost, increases sperm lifespan.
31337705	5	45	theme	each	746:749	arg1	versions					734:741	fluoresceinated versions	718:741	fluoresceinated versions of each	718:749	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	5	46	theme	trisaccharide	672:684	arg1	form					648:651	the 3'-O-sulfated form	630:651	the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A	630:707	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	5	47	theme	3'-O-sulfated	634:646	arg1	form					648:651	the 3'-O-sulfated form	630:651	the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A	630:707	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	9	48	dep	incubation	1624:1633	arg1	the					1620:1622	the	1620:1622	the	1620:1622	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	7	49	theme	suLeA	989:993	arg1	motifs					995:1000	suLeA motifs	989:1000	suLeA motifs	989:1000	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	0	50	theme	membrane	42:49	arg1	glycoproteins					51:63	oviduct membrane glycoproteins	34:63	oviduct membrane glycoproteins	34:63	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	4	51	theme	oviductal	519:527	arg1	glycans					529:535	oviductal glycans	519:535	oviductal glycans	519:535	Sperm lectins bind to oviductal glycans to form the reservoir.
31337705	8	52	dep	in	1192:1193	arg1	vivo					1195:1198	vivo	1195:1198	vivo	1195:1198	To determine whether sperm binding to isolated suLeAin vitro could mimic in vivo sperm binding to oviduct cells and increase sperm longevity, we immobilized suLeA and incubated it with sperm.
31337705	2	53	theme	fertile	321:327	arg1	population					329:338	a fertile population	319:338	a fertile population of sperm	319:347	This reservoir delays capacitation, prevents polyspermy, selects a fertile population of sperm, and, foremost, increases sperm lifespan.
31337705	6	54	theme	potential	877:885	arg1	explanation					887:897	a potential explanation	875:897	a potential explanation for sperm release from the reservoir	875:934	Following capacitation, binding to suLeA decreased significantly, a potential explanation for sperm release from the reservoir.
31337705	3	55	theme	reservoir	454:462	arg1	formation					433:441	the formation	429:441	the formation of a sperm reservoir	429:462	The molecular interactions underlying the formation of a sperm reservoir are becoming clearer in mammals.
31337705	5	56	theme	Lewis	656:660	arg1	suLeA					665:669	suLeA	665:669	suLeA	665:669	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	5	56	theme	Lewis	656:660	arg1	A					662:662	Lewis A	656:662	Lewis A (suLeA) trisaccharide	656:684	Herein, we found that the highest percentage of bovine sperm bound to the 3'-O-sulfated form of Lewis A (suLeA) trisaccharide and sialylated Lewis A and that fluoresceinated versions of each localized to receptors on the anterior head of the sperm.
31337705	1	57	theme	sperm	128:132	arg1	fraction					116:123	A fraction	114:123	A fraction of sperm deposited at mating or insemination	114:168	A fraction of sperm deposited at mating or insemination reaches the oviduct isthmus, where sperm are retained and thereby form a reservoir.
31337705	7	58	theme	GalNAc	1062:1067	arg1	residues					1069:1076	GalNAc residues	1062:1076	GalNAc residues	1062:1076	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	0	59	theme	bovine	71:76	arg1	sperm					78:82	bovine sperm	71:82	bovine sperm	71:82	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	9	60	from	h	1649:1649	arg1	incubation					1624:1633	incubation	1624:1633	incubation	1624:1633	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	9	60	from	h	1649:1649	arg1	%					1641:1641	60%	1639:1641	60%	1639:1641	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	7	61	theme	immunohistochemistry	944:963	arg1	analyses					965:972	MS and immunohistochemistry analyses	937:972	MS and immunohistochemistry analyses	937:972	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	10	62	theme	sperm	1768:1772	arg1	lifespan					1774:1781	sperm lifespan	1768:1781	sperm lifespan	1768:1781	These results indicate that bovine sperm binding to oviduct suLeA retains sperm for reservoir formation and extends sperm lifespan.
31337705	8	63	theme	in	1192:1193	arg1	binding					1206:1212	in vivo sperm binding	1192:1212	in vivo sperm binding to oviduct cells	1192:1229	To determine whether sperm binding to isolated suLeAin vitro could mimic in vivo sperm binding to oviduct cells and increase sperm longevity, we immobilized suLeA and incubated it with sperm.
31337705	0	64	from	trisaccharide	17:29	arg1	glycoproteins					51:63	oviduct membrane glycoproteins	34:63	oviduct membrane glycoproteins	34:63	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	0	65	gly	glycoproteins	51:63	arg1	glycoproteins					51:63	oviduct membrane glycoproteins	34:63	oviduct membrane glycoproteins	34:63	Sulfated Lewis A trisaccharide on oviduct membrane glycoproteins binds bovine sperm and lengthens sperm lifespan.
31337705	7	66	link	O-linked	1032:1039	arg1	glycans					1041:1047	O-linked glycans	1032:1047	O-linked glycans initiated by GalNAc residues	1032:1076	MS and immunohistochemistry analyses indicated that suLeA motifs were present predominantly on O-linked glycans initiated by GalNAc residues, but no sialylated Lewis A was detected.
31337705	9	67	theme	immobilized	1356:1366	arg1	laminin					1368:1374	immobilized laminin	1356:1374	immobilized laminin	1356:1374	Using free-swimming sperm and sperm bound to immobilized laminin as controls, we observed that over 96 h, the viability of free-swimming sperm decreased to 10%, and that of sperm bound to immobilized laminin decreased to about 50%, whereas viability of sperm bound to immobilized suLeA was highest throughout the incubation and 60% at 96 h.
31337705	8	68	dep	binding	1146:1152	arg1	isolated					1157:1164	isolated	1157:1164	to isolated suLeAin vitro	1154:1178	To determine whether sperm binding to isolated suLeAin vitro could mimic in vivo sperm binding to oviduct cells and increase sperm longevity, we immobilized suLeA and incubated it with sperm.
31029427	3	0	theme	previous	486:493	arg1	results					495:501	Our previous results	482:501	Our previous results	482:501	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	1	1	theme	transcription	228:240	arg1	factors					242:248	other transcription factors	222:248	other transcription factors	222:248	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	2	2	theme	cancer	462:467	arg1	progression					469:479	breast cancer progression	455:479	breast cancer progression	455:479	FOXA1 was reported to facilitate or reprogram ERα binding, thus playing a key function in breast cancer progression.
31029427	1	3	theme	downstream	330:339	arg1	expression					353:362	downstream target gene expression	330:362	downstream target gene expression	330:362	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	10	4	from	in vitro	1651:1658	arg1	ppGalNAc-T2					1631:1641	ppGalNAc-T2	1631:1641	ppGalNAc-T2 at S355 in vitro	1631:1658	In conclusion, our results demonstrated that FOXA1 can be O-GalNAcylated by ppGalNAc-T2 at S355 in vitro.
31029427	1	5	theme	transcriptional	136:150	arg1	regulation					152:161	transcriptional regulation	136:161	transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors	136:248	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	8	6	from	sites	1339:1343	arg1	FOXA1					1348:1352	FOXA1	1348:1352	FOXA1	1348:1352	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	9	7	theme	ESI-ETD-MS/MS	1382:1394	arg1	analysis					1396:1403	ESI-ETD-MS/MS analysis	1382:1403	ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein	1382:1451	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	0	8	theme	enzyme	80:85	arg1	in vitro					87:94	ppGalNAc-T2 enzyme in vitro	68:94	ppGalNAc-T2 enzyme in vitro	68:94	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	1	9	theme	target	341:346	arg1	expression					353:362	downstream target gene expression	330:362	downstream target gene expression	330:362	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	6	10	from	C-terminal	1023:1032	arg1	located					1008:1014	located	1008:1014	located	1008:1014	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	9	11	from	site	1502:1505	arg1	FOXA1					1510:1514	FOXA1	1510:1514	FOXA1	1510:1514	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	3	12	theme	N-acetylgalactosamine	531:551	arg1	modification					564:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification	518:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1	518:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	0	13	theme	ppGalNAc-T2	68:78	arg1	in vitro					87:94	ppGalNAc-T2 enzyme in vitro	68:94	ppGalNAc-T2 enzyme in vitro	68:94	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	1	14	theme	gene	348:351	arg1	expression					353:362	downstream target gene expression	330:362	downstream target gene expression	330:362	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	4	15	from	sites	782:786	arg1	FOXA1					791:795	FOXA1	791:795	FOXA1	791:795	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	16	theme	glycosylation	768:780	arg1	sites					782:786	the specific glycosylation sites	755:786	the specific glycosylation sites on FOXA1	755:795	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	16	theme	glycosylation	768:780	arg1	modification					738:749	modification	738:749	modification	738:749	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	9	17	theme	modification	1489:1500	arg1	site					1502:1505	the O-GalNAc modification site	1476:1505	the O-GalNAc modification site on FOXA1	1476:1514	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	9	17	theme	modification	1489:1500	arg1	S355					1468:1471	S355	1468:1471	S355	1468:1471	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	7	18	theme	vitro	1160:1164	arg1	reaction					1166:1173	a vitro reaction	1158:1173	a vitro reaction	1158:1173	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	1	19	theme	expression	353:362	arg1	regulation					316:325	the regulation	312:325	the regulation of downstream target gene expression	312:362	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	6	20	theme	protein	1041:1047	arg1	C-terminal					1023:1032	C-terminal	1023:1032	C-terminal	1023:1032	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	8	21	theme	probable	1314:1321	arg1	sites					1339:1343	probable O-GalNAcylation sites	1314:1343	probable O-GalNAcylation sites on FOXA1	1314:1352	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	8	21	theme	probable	1314:1321	arg1	S355					1290:1293	S355	1290:1293	S355	1290:1293	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	8	21	theme	probable	1314:1321	arg1	S354					1281:1284	S354	1281:1284	S354	1281:1284	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	9	22	theme	O-GalNAcylated	1424:1437	arg1	protein					1445:1451	the full-length O-GalNAcylated FOXA1 protein	1408:1451	the full-length O-GalNAcylated FOXA1 protein	1408:1451	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	1	23	theme	regulation	152:161	arg1	factor					126:131	a pioneer factor	116:131	a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors	116:248	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	1	23	theme	regulation	152:161	arg1	FOXA1					97:101	FOXA1	97:101	FOXA1	97:101	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	0	24	theme	s	43:43	arg1	Identification					0:13	Identification	0:13	Identification of the O-GalNAcylation site(s) on FOXA1	0:53	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	7	25	theme	FOXA1	1138:1142	arg1	C-terminus					1124:1133	the C-terminus	1120:1133	the C-terminus of FOXA1	1120:1142	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	3	26	theme	O-linked	522:529	arg1	modification					564:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification	518:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1	518:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	9	27	theme	full-length	1412:1422	arg1	protein					1445:1451	the full-length O-GalNAcylated FOXA1 protein	1408:1451	the full-length O-GalNAcylated FOXA1 protein	1408:1451	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	6	28	theme	O-GalNAcylation	960:974	arg1	sites					976:980	two O-GalNAcylation sites	956:980	two O-GalNAcylation sites	956:980	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	0	29	from	s	43:43	arg1	FOXA1					49:53	FOXA1	49:53	FOXA1	49:53	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	5	30	theme	ppGalNAc-T2	870:880	arg1	in vitro					882:889	ppGalNAc-T2 in vitro	870:889	ppGalNAc-T2 in vitro	870:889	In this study, we first suggested that FOXA1 could be O-GalNAcylated by ppGalNAc-T2 in vitro.
31029427	6	31	theme	recombinant	919:929	arg1	FOXA1					931:935	recombinant FOXA1	919:935	recombinant FOXA1	919:935	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	6	31	theme	recombinant	919:929	arg1	segments					946:953	three segments	940:953	three segments	940:953	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	4	32	theme	modification	738:749	arg1	sites					782:786	the specific glycosylation sites	755:786	the specific glycosylation sites on FOXA1	755:795	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	32	theme	modification	738:749	arg1	modification					738:749	modification	738:749	modification	738:749	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	32	theme	modification	738:749	arg1	mechanism					725:733	the specific mechanism	712:733	the specific mechanism of modification	712:749	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	33	theme	further	666:672	arg1	investigations					674:687	further investigations	666:687	further investigations	666:687	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	0	34	theme	O-GalNAcylation	22:36	arg1	s					43:43	the O-GalNAcylation site(s)	18:44	the O-GalNAcylation site(s) on FOXA1	18:53	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	7	35	used	used	1150:1153	arg2	peptides					1068:1075	synthesized peptides	1056:1075	synthesized peptides	1056:1075	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	7	35	used	used	1150:1153	arg2	sites					1111:1115	the predicted O-GalNAc sites	1088:1115	the predicted O-GalNAc sites in the C-terminus of FOXA1	1088:1142	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	3	36	theme	O-GalNAc	554:561	arg1	modification					564:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification	518:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1	518:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	7	37	theme	predicted	1092:1100	arg1	sites					1111:1115	the predicted O-GalNAc sites	1088:1115	the predicted O-GalNAc sites in the C-terminus of FOXA1	1088:1142	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	1	38	theme	specific	177:184	arg1	sites					186:190	specific sites	177:190	specific sites in the chromatin	177:207	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	8	39	theme	O-GalNAcylation	1323:1337	arg1	sites					1339:1343	probable O-GalNAcylation sites	1314:1343	probable O-GalNAcylation sites on FOXA1	1314:1352	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	8	39	theme	O-GalNAcylation	1323:1337	arg1	S355					1290:1293	S355	1290:1293	S355	1290:1293	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	8	39	theme	O-GalNAcylation	1323:1337	arg1	S354					1281:1284	S354	1281:1284	S354	1281:1284	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	11	40	theme	cancer	1771:1776	arg1	development					1749:1759	the development	1745:1759	the development of breast cancer	1745:1776	These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer.
31029427	7	41	theme	O-GalNAc	1214:1221	arg1	sites					1223:1227	the predicted O-GalNAc sites	1200:1227	the predicted O-GalNAc sites	1200:1227	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	2	42	theme	ERα	411:413	arg1	binding					415:421	ERα binding	411:421	ERα binding	411:421	FOXA1 was reported to facilitate or reprogram ERα binding, thus playing a key function in breast cancer progression.
31029427	2	43	theme	breast	455:460	arg1	progression					469:479	breast cancer progression	455:479	breast cancer progression	455:479	FOXA1 was reported to facilitate or reprogram ERα binding, thus playing a key function in breast cancer progression.
31029427	1	44	theme	gene	279:282	arg1	transcription					284:296	gene transcription	279:296	gene transcription	279:296	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	11	45	theme	new	1688:1690	arg1	insights					1692:1699	new insights	1688:1699	new insights for studying the role of O-GalNAcylation in the development of breast cancer	1688:1776	These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer.
31029427	9	46	theme	FOXA1	1439:1443	arg1	protein					1445:1451	the full-length O-GalNAcylated FOXA1 protein	1408:1451	the full-length O-GalNAcylated FOXA1 protein	1408:1451	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	0	47	theme	site	38:41	arg1	s					43:43	the O-GalNAcylation site(s)	18:44	the O-GalNAcylation site(s) on FOXA1	18:53	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	1	48	theme	transcription	284:296	arg1	initiation					265:274	the initiation	261:274	the initiation of gene transcription	261:296	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	11	49	theme	breast	1764:1769	arg1	cancer					1771:1776	breast cancer	1764:1776	breast cancer	1764:1776	These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer.
31029427	0	50	from	FOXA1	49:53	arg1	Identification					0:13	Identification	0:13	Identification of the O-GalNAcylation site(s) on FOXA1	0:53	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	10	51	theme	S355	1646:1649	arg1	in vitro					1651:1658	S355 in vitro	1646:1658	S355 in vitro	1646:1658	In conclusion, our results demonstrated that FOXA1 can be O-GalNAcylated by ppGalNAc-T2 at S355 in vitro.
31029427	9	52	with	consistent	1517:1526	arg1	reaction					1545:1552	the peptide reaction	1533:1552	the peptide reaction	1533:1552	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	7	53	from	sites	1111:1115	arg1	C-terminus					1124:1133	the C-terminus	1120:1133	the C-terminus of FOXA1	1120:1142	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	11	54	from	role	1718:1721	arg1	development					1749:1759	the development	1745:1759	the development of breast cancer	1745:1776	These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer.
31029427	3	55	theme	transcription	634:646	arg1	network					648:654	the ERα transcription network	626:654	the ERα transcription network	626:654	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	3	56	theme	FOXA1	580:584	arg1	modification					564:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification	518:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1	518:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	4	57	theme	specific	716:723	arg1	mechanism					725:733	the specific mechanism	712:733	the specific mechanism of modification	712:749	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	0	58	from	Identification	0:13	arg1	FOXA1					49:53	FOXA1	49:53	FOXA1	49:53	Identification of the O-GalNAcylation site(s) on FOXA1 catalyzed by ppGalNAc-T2 enzyme in vitro.
31029427	7	59	theme	synthesized	1056:1066	arg1	sites					1111:1115	the predicted O-GalNAc sites	1088:1115	the predicted O-GalNAc sites in the C-terminus of FOXA1	1088:1142	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	7	59	theme	synthesized	1056:1066	arg1	peptides					1068:1075	synthesized peptides	1056:1075	synthesized peptides	1056:1075	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	2	60	theme	key	439:441	arg1	function					443:450	a key function	437:450	a key function	437:450	FOXA1 was reported to facilitate or reprogram ERα binding, thus playing a key function in breast cancer progression.
31029427	3	61	mod	modification	564:575	arg1	FOXA1					580:584	FOXA1	580:584	FOXA1	580:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	3	61	mod	modification	564:575	arg3	O-GalNAc					554:561	the O-linked N-acetylgalactosamine (O-GalNAc) modification	518:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1	518:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	3	61	mod	modification	564:575	arg3	N-acetylgalactosamine					531:551	the O-linked N-acetylgalactosamine (O-GalNAc) modification	518:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1	518:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	3	62	theme	ERα	630:632	arg1	network					648:654	the ERα transcription network	626:654	the ERα transcription network	626:654	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	3	63	link	O-linked	522:529	arg1	modification					564:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification	518:575	the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1	518:584	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	1	64	from	sites	186:190	arg1	chromatin					199:207	the chromatin	195:207	the chromatin	195:207	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	9	65	theme	O-GalNAc	1480:1487	arg1	site					1502:1505	the O-GalNAc modification site	1476:1505	the O-GalNAc modification site on FOXA1	1476:1514	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	9	65	theme	O-GalNAc	1480:1487	arg1	S355					1468:1471	S355	1468:1471	S355	1468:1471	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	4	66	theme	specific	759:766	arg1	sites					782:786	the specific glycosylation sites	755:786	the specific glycosylation sites on FOXA1	755:795	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	66	theme	specific	759:766	arg1	modification					738:749	modification	738:749	modification	738:749	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	11	67	theme	O-GalNAcylation	1726:1740	arg1	role					1718:1721	the role	1714:1721	the role of O-GalNAcylation in the development of breast cancer	1714:1776	These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer.
31029427	9	68	theme	peptide	1537:1543	arg1	reaction					1545:1552	the peptide reaction	1533:1552	the peptide reaction	1533:1552	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	6	69	located	found	987:991	arg2	sites					976:980	two O-GalNAcylation sites	956:980	two O-GalNAcylation sites	956:980	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	6	69	located	found	987:991	arg1	both					1003:1006	both	1003:1006	both	1003:1006	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	6	69	located	found	987:991	arg1	FOXA1					996:1000	FOXA1	996:1000	FOXA1	996:1000	By dividing and expressing recombinant FOXA1 as three segments, two O-GalNAcylation sites were found on FOXA1, both located at the C-terminal of the protein.
31029427	7	70	theme	O-GalNAc	1102:1109	arg1	sites					1111:1115	the predicted O-GalNAc sites	1088:1115	the predicted O-GalNAc sites in the C-terminus of FOXA1	1088:1142	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	8	71	theme	ESI-MS	1267:1272	arg1	assay					1274:1278	an ESI-MS assay	1264:1278	an ESI-MS assay	1264:1278	Through an ESI-MS assay, S354 and S355 were identified as probable O-GalNAcylation sites on FOXA1.
31029427	4	72	gly	glycosylation	768:780	arg2	modification					738:749	modification	738:749	modification	738:749	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	72	gly	glycosylation	768:780	arg2	sites					782:786	the specific glycosylation sites	755:786	the specific glycosylation sites on FOXA1	755:795	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	4	72	gly	glycosylation	768:780	arg1	modification					738:749	modification	738:749	modification	738:749	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	3	73	theme	significant	606:616	arg1	role					618:621	a potentially significant role	592:621	a potentially significant role	592:621	Our previous results indicated that the O-linked N-acetylgalactosamine (O-GalNAc) modification of FOXA1 plays a potentially significant role in the ERα transcription network.
31029427	9	74	theme	protein	1445:1451	arg1	analysis					1396:1403	ESI-ETD-MS/MS analysis	1382:1403	ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein	1382:1451	Additionally, we performed ESI-ETD-MS/MS analysis of the full-length O-GalNAcylated FOXA1 protein and identified S355 as the O-GalNAc modification site on FOXA1, consistent with the peptide reaction.
31029427	1	75	theme	pioneer	118:124	arg1	factor					126:131	a pioneer factor	116:131	a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors	116:248	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	1	75	theme	pioneer	118:124	arg1	FOXA1					97:101	FOXA1	97:101	FOXA1	97:101	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
31029427	4	76	from	mechanism	725:733	arg1	FOXA1					791:795	FOXA1	791:795	FOXA1	791:795	However, further investigations are needed to identify the specific mechanism of modification and the specific glycosylation sites on FOXA1.
31029427	11	77	dep	provide	1680:1686	arg1	will					1675:1678	will	1675:1678	will	1675:1678	These results will provide new insights for studying the role of O-GalNAcylation in the development of breast cancer.
31029427	7	78	theme	predicted	1204:1212	arg1	sites					1223:1227	the predicted O-GalNAc sites	1200:1227	the predicted O-GalNAc sites	1200:1227	Then, synthesized peptides, including the predicted O-GalNAc sites in the C-terminus of FOXA1, were used in a vitro reaction, and peptides mutated at the predicted O-GalNAc sites were employed as controls.
31029427	1	79	theme	other	222:226	arg1	factors					242:248	other transcription factors	222:248	other transcription factors	222:248	FOXA1 functions as a pioneer factor of transcriptional regulation that binds to specific sites in the chromatin and recruits other transcription factors, promoting the initiation of gene transcription and mediating the regulation of downstream target gene expression.
30758674	4	0	theme	reactive	549:556	arg1	ROS					574:576	ROS	574:576	ROS	574:576	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	4	0	theme	reactive	549:556	arg1	species					565:571	reactive oxygen species	549:571	reactive oxygen species (ROS)	549:577	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	7	1	theme	psl	1138:1140	arg1	mutant					1142:1147	psl mutant	1138:1147	psl mutant	1138:1147	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	9	2	with	Consistent	1407:1416	arg1	results					1437:1443	the proteomic results	1423:1443	the proteomic results	1423:1443	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	4	3	theme	species	565:571	arg1	accumulation					533:544	elevated accumulation	524:544	elevated accumulation of reactive oxygen species (ROS)	524:577	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	5	4	from	deletion	671:678	arg1	LOC_Os12g42420					694:707	LOC_Os12g42420	694:707	LOC_Os12g42420	694:707	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	5	4	from	deletion	671:678	arg1	OsPSL					687:691	the OsPSL	683:691	the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	683:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	5	4	from	deletion	671:678	arg1	2/I					738:740	a putative core 2/I	722:740	a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	722:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	2	5	theme	leaf	256:259	arg1	senescence					261:270	leaf senescence	256:270	leaf senescence	256:270	Although it has been extensively studied, the mechanism of leaf senescence is not well understood.
30758674	1	6	theme	complex	168:174	arg1	senescence					122:131	Leaf senescence	117:131	Leaf senescence	117:131	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	1	6	theme	complex	168:174	arg1	process					188:194	a genetically regulated, highly complex and ordered process	136:194	a genetically regulated, highly complex and ordered process	136:194	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	8	7	theme	methionine	1305:1314	arg1	SAMS					1334:1337	SAMS	1334:1337	SAMS	1334:1337	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	8	7	theme	methionine	1305:1314	arg1	synthetase					1322:1331	S-adenosyl methionine (SAM) synthetase	1294:1331	S-adenosyl methionine (SAM) synthetase (SAMS)	1294:1338	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	10	8	theme	leaf	1631:1634	arg1	senescence					1636:1645	The early leaf senescence	1621:1645	The early leaf senescence of psl	1621:1652	The early leaf senescence of psl can be partially rescued by ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment.
30758674	11	9	theme	possible	1857:1864	arg1	role					1866:1869	a possible role	1855:1869	a possible role of OsPSL in ethylene signaling	1855:1900	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	1	10	theme	ordered	180:186	arg1	senescence					122:131	Leaf senescence	117:131	Leaf senescence	117:131	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	1	10	theme	ordered	180:186	arg1	process					188:194	a genetically regulated, highly complex and ordered process	136:194	a genetically regulated, highly complex and ordered process	136:194	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	7	11	theme	transferases	1095:1106	arg1	levels					1045:1050	transcriptional levels	1029:1050	transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification	1029:1215	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	9	12	theme	wild-type	1501:1509	arg1	plants					1511:1516	wild-type plants	1501:1516	wild-type plants	1501:1516	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	6	13	theme	late	956:959	arg1	stages					972:977	late senescence stages	956:977	late senescence stages in WT plants	956:990	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	5	14	theme	glycosylation	830:842	arg1	modification					844:855	protein glycosylation modification	822:855	protein glycosylation modification	822:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	8	15	theme	metabolic	1266:1274	arg1	enzymes					1276:1282	ethylene-related metabolic enzymes	1249:1282	ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS)	1249:1338	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	8	15	theme	metabolic	1266:1274	arg1	synthetase					1322:1331	S-adenosyl methionine (SAM) synthetase	1294:1331	S-adenosyl methionine (SAM) synthetase (SAMS)	1294:1338	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	6	16	theme	transcripts	941:951	arg1	accumulation					925:936	maximum accumulation	917:936	maximum accumulation of transcripts at late senescence stages in WT plants	917:990	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	7	17	theme	N-acetylglucosamine	1064:1082	arg1	OGTs					1109:1112	OGTs	1109:1112	OGTs	1109:1112	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	7	17	theme	N-acetylglucosamine	1064:1082	arg1	transferases					1095:1106	O-linked N-acetylglucosamine (O-GlcNAc) transferases	1055:1106	O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs)	1055:1113	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	1	18	theme	Leaf	117:120	arg1	senescence					122:131	Leaf senescence	117:131	Leaf senescence	117:131	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	1	18	theme	Leaf	117:120	arg1	process					188:194	a genetically regulated, highly complex and ordered process	136:194	a genetically regulated, highly complex and ordered process	136:194	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	11	19	theme	O-glycosylation	1799:1813	arg1	importance					1777:1786	the importance	1773:1786	the importance of protein O-glycosylation in PCD and leaf senescence	1773:1840	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	0	20	theme	cell	71:74	arg1	death					76:80	programmed cell death	60:80	programmed cell death	60:80	Mutation in a putative glycosyltransferase-like gene causes programmed cell death and early leaf senescence in rice.
30758674	9	21	theme	synthesis	1553:1561	arg1	levels					1534:1539	transcript levels	1523:1539	transcript levels of ethylene synthesis and signal transduction genes	1523:1591	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	5	22	theme	putative	724:731	arg1	OsPSL					687:691	the OsPSL	683:691	the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	683:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	5	22	theme	putative	724:731	arg1	2/I					738:740	a putative core 2/I	722:740	a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	722:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	9	23	theme	signal	1567:1572	arg1	transduction					1574:1585	signal transduction	1567:1585	signal transduction	1567:1585	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	3	24	theme	rice	325:328	arg1	mutant					330:335	a rice mutant	323:335	a rice mutant	323:335	In this study, we isolated a rice mutant, designated as premature senescence leaf (psl), which exhibits early senescence and spontaneous lesion mimic phenotype after flowering.
30758674	0	25	from	Mutation	0:7	arg1	gene					48:51	a putative glycosyltransferase-like gene	12:51	a putative glycosyltransferase-like gene	12:51	Mutation in a putative glycosyltransferase-like gene causes programmed cell death and early leaf senescence in rice.
30758674	11	26	theme	leaf	1826:1829	arg1	senescence					1831:1840	leaf senescence	1826:1840	leaf senescence	1826:1840	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	0	27	theme	leaf	92:95	arg1	senescence					97:106	early leaf senescence	86:106	early leaf senescence	86:106	Mutation in a putative glycosyltransferase-like gene causes programmed cell death and early leaf senescence in rice.
30758674	6	28	theme	WT	982:983	arg1	plants					985:990	WT plants	982:990	WT plants	982:990	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	3	29	dep	senescence	362:371	arg1	leaf					373:376	leaf	373:376	premature senescence leaf (psl)	352:382	In this study, we isolated a rice mutant, designated as premature senescence leaf (psl), which exhibits early senescence and spontaneous lesion mimic phenotype after flowering.
30758674	3	29	dep	senescence	362:371	arg1	psl					379:381	psl	379:381	psl	379:381	In this study, we isolated a rice mutant, designated as premature senescence leaf (psl), which exhibits early senescence and spontaneous lesion mimic phenotype after flowering.
30758674	10	30	theme	aminoethoxyvinylglycine	1714:1736	arg1	treatment					1738:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	The early leaf senescence of psl can be partially rescued by ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment.
30758674	10	31	theme	ethylene	1682:1689	arg1	treatment					1738:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	The early leaf senescence of psl can be partially rescued by ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment.
30758674	7	32	theme	O-glycosylation	1188:1202	arg1	modification					1204:1215	impaired O-glycosylation modification	1179:1215	impaired O-glycosylation modification	1179:1215	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	9	33	theme	psl	1609:1611	arg1	mutant					1613:1618	psl mutant	1609:1618	psl mutant	1609:1618	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	6	34	theme	mRNA	864:867	arg1	levels					869:874	OsPSL mRNA levels	858:874	OsPSL mRNA levels	858:874	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	4	35	theme	elevated	524:531	arg1	accumulation					533:544	elevated accumulation	524:544	elevated accumulation of reactive oxygen species (ROS)	524:577	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	3	36	theme	early	400:404	arg1	senescence					406:415	early senescence	400:415	early senescence	400:415	In this study, we isolated a rice mutant, designated as premature senescence leaf (psl), which exhibits early senescence and spontaneous lesion mimic phenotype after flowering.
30758674	10	37	theme	inhibitor	1704:1712	arg1	treatment					1738:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	The early leaf senescence of psl can be partially rescued by ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment.
30758674	0	38	theme	glycosyltransferase-like	23:46	arg1	gene					48:51	a putative glycosyltransferase-like gene	12:51	a putative glycosyltransferase-like gene	12:51	Mutation in a putative glycosyltransferase-like gene causes programmed cell death and early leaf senescence in rice.
30758674	5	39	theme	beta-1,6-N-acetylglucosaminyl	752:780	arg1	transferase					782:792	beta-1,6-N-acetylglucosaminyl transferase	752:792	beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	752:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	4	40	theme	programmed	497:506	arg1	death					513:517	programmed cell death	497:517	programmed cell death	497:517	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	11	41	theme	protein	1791:1797	arg1	O-glycosylation					1799:1813	protein O-glycosylation	1791:1813	protein O-glycosylation	1791:1813	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	7	42	link	O-linked	1055:1062	arg1	O-GlcNAc					1085:1092	O-GlcNAc	1085:1092	O-GlcNAc	1085:1092	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	7	42	link	O-linked	1055:1062	arg1	N-acetylglucosamine					1064:1082	O-linked N-acetylglucosamine	1055:1082	O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs)	1055:1113	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	3	43	dep	senescence	406:415	arg1	mimic					440:444	mimic	440:444	mimic phenotype after flowering	440:470	In this study, we isolated a rice mutant, designated as premature senescence leaf (psl), which exhibits early senescence and spontaneous lesion mimic phenotype after flowering.
30758674	9	44	theme	psl	1482:1484	arg1	mutant					1486:1491	psl mutant	1482:1491	psl mutant	1482:1491	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	6	45	theme	maximum	917:923	arg1	accumulation					925:936	maximum accumulation	917:936	maximum accumulation of transcripts at late senescence stages in WT plants	917:990	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	9	46	theme	ethylene	1446:1453	arg1	concentration					1455:1467	ethylene concentration	1446:1467	ethylene concentration	1446:1467	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	7	47	dep	levels	1045:1050	arg1	observed					1126:1133	observed	1126:1133	observed	1126:1133	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	6	48	theme	senescence	889:898	arg1	progressed					900:909	senescence progressed	889:909	senescence progressed	889:909	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	4	49	theme	oxygen	558:563	arg1	ROS					574:576	ROS	574:576	ROS	574:576	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	4	49	theme	oxygen	558:563	arg1	species					565:571	reactive oxygen species	549:571	reactive oxygen species (ROS)	549:577	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	5	50	theme	Molecular	580:588	arg1	analyses					602:609	Molecular and genetic analyses	580:609	Molecular and genetic analyses	580:609	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	2	51	theme	senescence	261:270	arg1	mechanism					243:251	the mechanism	239:251	the mechanism of leaf senescence	239:270	Although it has been extensively studied, the mechanism of leaf senescence is not well understood.
30758674	5	52	theme	genetic	594:600	arg1	analyses					602:609	Molecular and genetic analyses	580:609	Molecular and genetic analyses	580:609	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	11	53	from	role	1866:1869	arg1	signaling					1892:1900	ethylene signaling	1883:1900	ethylene signaling	1883:1900	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	8	54	theme	S-adenosyl	1294:1303	arg1	SAM					1317:1319	SAM	1317:1319	SAM	1317:1319	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	8	54	theme	S-adenosyl	1294:1303	arg1	methionine					1305:1314	S-adenosyl methionine	1294:1314	S-adenosyl methionine (SAM) synthetase (SAMS)	1294:1338	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	10	55	theme	early	1625:1629	arg1	senescence					1636:1645	The early leaf senescence	1621:1645	The early leaf senescence of psl	1621:1652	The early leaf senescence of psl can be partially rescued by ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment.
30758674	5	56	theme	phenylalanine	657:669	arg1	deletion					671:678	a phenylalanine deletion	655:678	a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	655:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	8	57	theme	Proteomic	1218:1226	arg1	analysis					1228:1235	Proteomic analysis	1218:1235	Proteomic analysis	1218:1235	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	6	58	theme	senescence	961:970	arg1	stages					972:977	late senescence stages	956:977	late senescence stages in WT plants	956:990	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	5	59	theme	protein	822:828	arg1	modification					844:855	protein glycosylation modification	822:855	protein glycosylation modification	822:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	10	60	theme	psl	1650:1652	arg1	senescence					1636:1645	The early leaf senescence	1621:1645	The early leaf senescence of psl	1621:1652	The early leaf senescence of psl can be partially rescued by ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment.
30758674	11	61	theme	ethylene	1883:1890	arg1	signaling					1892:1900	ethylene signaling	1883:1900	ethylene signaling	1883:1900	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	7	62	theme	O-linked	1055:1062	arg1	O-GlcNAc					1085:1092	O-GlcNAc	1085:1092	O-GlcNAc	1085:1092	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	7	62	theme	O-linked	1055:1062	arg1	N-acetylglucosamine					1064:1082	O-linked N-acetylglucosamine	1055:1082	O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs)	1055:1113	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	7	63	theme	transcriptional	1029:1043	arg1	levels					1045:1050	transcriptional levels	1029:1050	transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification	1029:1215	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	8	64	theme	ethylene-related	1249:1264	arg1	enzymes					1276:1282	ethylene-related metabolic enzymes	1249:1282	ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS)	1249:1338	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	8	64	theme	ethylene-related	1249:1264	arg1	synthetase					1322:1331	S-adenosyl methionine (SAM) synthetase	1294:1331	S-adenosyl methionine (SAM) synthetase (SAMS)	1294:1338	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	11	65	theme	OsPSL	1874:1878	arg1	role					1866:1869	a possible role	1855:1869	a possible role of OsPSL in ethylene signaling	1855:1900	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	9	66	theme	ethylene	1544:1551	arg1	synthesis					1553:1561	ethylene synthesis	1544:1561	ethylene synthesis	1544:1561	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	11	67	from	importance	1777:1786	arg1	PCD					1818:1820	PCD	1818:1820	PCD	1818:1820	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	11	67	from	importance	1777:1786	arg1	senescence					1831:1840	leaf senescence	1826:1840	leaf senescence	1826:1840	These results highlight the importance of protein O-glycosylation in PCD and leaf senescence, and suggest a possible role of OsPSL in ethylene signaling.
30758674	0	68	theme	early	86:90	arg1	senescence					97:106	early leaf senescence	86:106	early leaf senescence	86:106	Mutation in a putative glycosyltransferase-like gene causes programmed cell death and early leaf senescence in rice.
30758674	1	69	theme	regulated	150:158	arg1	senescence					122:131	Leaf senescence	117:131	Leaf senescence	117:131	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	1	69	theme	regulated	150:158	arg1	process					188:194	a genetically regulated, highly complex and ordered process	136:194	a genetically regulated, highly complex and ordered process	136:194	Leaf senescence is a genetically regulated, highly complex and ordered process.
30758674	4	70	theme	psl	477:479	arg1	mutant					481:486	The psl mutant	473:486	The psl mutant	473:486	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	7	71	located	observed	1126:1133	arg1	mutant					1142:1147	psl mutant	1138:1147	psl mutant	1138:1147	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	7	71	located	observed	1126:1133	arg2	genes					1115:1119	genes	1115:1119	genes	1115:1119	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	9	72	theme	transduction	1574:1585	arg1	levels					1534:1539	transcript levels	1523:1539	transcript levels of ethylene synthesis and signal transduction genes	1523:1591	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	8	73	theme	psl	1378:1380	arg1	mutant					1382:1387	the psl mutant	1374:1387	the psl mutant	1374:1387	Proteomic analysis showed that ethylene-related metabolic enzymes including S-adenosyl methionine (SAM) synthetase (SAMS) were significantly upregulated in the psl mutant compared with WT.
30758674	7	74	theme	modification	1204:1215	arg1	occurrence					1165:1174	the occurrence	1161:1174	the occurrence of impaired O-glycosylation modification	1161:1215	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	9	75	theme	transcript	1523:1532	arg1	levels					1534:1539	transcript levels	1523:1539	transcript levels of ethylene synthesis and signal transduction genes	1523:1591	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	7	76	theme	impaired	1179:1186	arg1	modification					1204:1215	impaired O-glycosylation modification	1179:1215	impaired O-glycosylation modification	1179:1215	Moreover, remarkedly down-regulated transcriptional levels of O-linked N-acetylglucosamine (O-GlcNAc) transferases (OGTs) genes were observed in psl mutant, supporting the occurrence of impaired O-glycosylation modification.
30758674	3	77	theme	premature	352:360	arg1	senescence					362:371	premature senescence leaf (psl)	352:382	premature senescence leaf (psl)	352:382	In this study, we isolated a rice mutant, designated as premature senescence leaf (psl), which exhibits early senescence and spontaneous lesion mimic phenotype after flowering.
30758674	0	78	theme	putative	14:21	arg1	gene					48:51	a putative glycosyltransferase-like gene	12:51	a putative glycosyltransferase-like gene	12:51	Mutation in a putative glycosyltransferase-like gene causes programmed cell death and early leaf senescence in rice.
30758674	9	79	dep	synthesis	1553:1561	arg1	genes					1587:1591	genes	1587:1591	genes	1587:1591	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30758674	3	80	theme	spontaneous	421:431	arg1	lesion					433:438	spontaneous lesion	421:438	spontaneous lesion	421:438	In this study, we isolated a rice mutant, designated as premature senescence leaf (psl), which exhibits early senescence and spontaneous lesion mimic phenotype after flowering.
30758674	5	81	theme	core	733:736	arg1	OsPSL					687:691	the OsPSL	683:691	the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	683:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	5	81	theme	core	733:736	arg1	2/I					738:740	a putative core 2/I	722:740	a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification	722:855	Molecular and genetic analyses revealed that the phenotypes were caused by a phenylalanine deletion in the OsPSL (LOC_Os12g42420) that encode a putative core 2/I branching beta-1,6-N-acetylglucosaminyl transferase predicted to be involved in protein glycosylation modification.
30758674	6	82	theme	OsPSL	858:862	arg1	levels					869:874	OsPSL mRNA levels	858:874	OsPSL mRNA levels	858:874	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	6	83	from	stages	972:977	arg1	accumulation					925:936	maximum accumulation	917:936	maximum accumulation of transcripts at late senescence stages in WT plants	917:990	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	6	83	from	stages	972:977	arg1	plants					985:990	WT plants	982:990	WT plants	982:990	OsPSL mRNA levels increased as senescence progressed, with maximum accumulation of transcripts at late senescence stages in WT plants.
30758674	10	84	theme	biosynthesis	1691:1702	arg1	treatment					1738:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment	1682:1746	The early leaf senescence of psl can be partially rescued by ethylene biosynthesis inhibitor aminoethoxyvinylglycine treatment.
30758674	0	85	theme	programmed	60:69	arg1	death					76:80	programmed cell death	60:80	programmed cell death	60:80	Mutation in a putative glycosyltransferase-like gene causes programmed cell death and early leaf senescence in rice.
30758674	4	86	theme	cell	508:511	arg1	death					513:517	programmed cell death	497:517	programmed cell death	497:517	The psl mutant displays programmed cell death with elevated accumulation of reactive oxygen species (ROS).
30758674	9	87	theme	proteomic	1427:1435	arg1	results					1437:1443	the proteomic results	1423:1443	the proteomic results	1423:1443	Consistent with the proteomic results, ethylene concentration is higher in psl mutant than in wild-type plants, and transcript levels of ethylene synthesis and signal transduction genes were induced in psl mutant.
30186544	7	0	theme	reactive	1208:1215	arg1	species					1224:1230	reactive oxygen species	1208:1230	reactive oxygen species	1208:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	1	theme	RIPC-induced	1067:1078	arg1	elevation					1080:1088	RIPC-induced elevation	1067:1088	RIPC-induced elevation of O-GlcNAc signaling	1067:1110	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	3	2	theme	acute	564:568	arg1	increase					570:577	an acute increase	561:577	an acute increase	561:577	Growing evidence indicates that stress can induce an acute increase in O-GlcNAc levels, which can be cytoprotective.
30186544	3	2	theme	acute	564:568	arg1	cytoprotective					612:625	cytoprotective	612:625	cytoprotective	612:625	Growing evidence indicates that stress can induce an acute increase in O-GlcNAc levels, which can be cytoprotective.
30186544	7	3	theme	oxygen	1217:1222	arg1	species					1224:1230	reactive oxygen species	1208:1230	reactive oxygen species	1208:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	2	4	theme	proteins	385:392	arg1	glycosylation					354:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation	312:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins	312:392	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	1	5	theme	adjacent	273:280	arg1	tissues					293:299	tissues	293:299	tissues	293:299	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	3	6	from	increase	570:577	arg1	levels					591:596	O-GlcNAc levels	582:596	O-GlcNAc levels	582:596	Growing evidence indicates that stress can induce an acute increase in O-GlcNAc levels, which can be cytoprotective.
30186544	9	7	theme	tubular	1525:1531	arg1	apoptosis					1533:1541	tubular apoptosis	1525:1541	tubular apoptosis	1525:1541	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	6	8	theme	UDP-GlcNAc	964:973	arg1	levels					975:980	UDP-GlcNAc levels	964:980	UDP-GlcNAc levels	964:980	We found that RIPC increased UDP-GlcNAc levels through the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation.
30186544	8	9	theme	tubular	1448:1454	arg1	apoptosis					1456:1464	tubular apoptosis	1448:1464	tubular apoptosis	1448:1464	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	8	10	theme	oxidative	1427:1435	arg1	stress					1437:1442	oxidative stress	1427:1442	oxidative stress	1427:1442	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	1	11	theme	distant	285:291	arg1	tissues					293:299	tissues	293:299	tissues	293:299	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	5	12	theme	stable	810:815	arg1	model					817:821	a stable model	808:821	a stable model of CI-AKI	808:831	We established a stable model of CI-AKI using 5/6 nephrectomized rats exposed to dehydration followed by iohexol injection via the tail vein.
30186544	0	13	from	Injury	57:62	arg1	Rats					92:95	Rats	92:95	Rats	92:95	Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.
30186544	8	14	theme	fructose-6-phosphate	1328:1347	arg1	amidotransferase					1349:1364	a glutamine fructose-6-phosphate amidotransferase	1316:1364	a glutamine fructose-6-phosphate amidotransferase inhibitor	1316:1374	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	8	15	theme	glutamine	1318:1326	arg1	amidotransferase					1349:1364	a glutamine fructose-6-phosphate amidotransferase	1316:1364	a glutamine fructose-6-phosphate amidotransferase inhibitor	1316:1374	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	4	16	theme	kidney	736:741	arg1	CI-AKI					751:756	CI-AKI	751:756	CI-AKI	751:756	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	4	16	theme	kidney	736:741	arg1	injury					743:748	contrast-induced acute kidney injury	713:748	contrast-induced acute kidney injury (CI-AKI)	713:757	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	0	17	theme	Augmented	105:113	arg1	O-GlcNAcylation					115:129	Augmented O-GlcNAcylation	105:129	Augmented O-GlcNAcylation	105:129	Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.
30186544	5	18	theme	nephrectomized	843:856	arg1	rats					858:861	5/6 nephrectomized rats	839:861	5/6 nephrectomized rats exposed to dehydration followed by iohexol injection via the tail vein	839:932	We established a stable model of CI-AKI using 5/6 nephrectomized rats exposed to dehydration followed by iohexol injection via the tail vein.
30186544	8	19	theme	alloxan	1257:1263	arg1	use					1250:1252	the use	1246:1252	the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor,	1246:1375	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	1	20	theme	adaptive	177:184	arg1	response					186:193	an adaptive response	174:193	an adaptive response	174:193	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	1	20	theme	adaptive	177:184	arg1	preconditioning					148:162	Remote ischemic preconditioning	132:162	Remote ischemic preconditioning (RIPC)	132:169	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	0	21	theme	Ischemic	7:14	arg1	Preconditioning					16:30	Remote Ischemic Preconditioning	0:30	Remote Ischemic Preconditioning	0:30	Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.
30186544	4	22	theme	acute	730:734	arg1	CI-AKI					751:756	CI-AKI	751:756	CI-AKI	751:756	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	4	22	theme	acute	730:734	arg1	injury					743:748	contrast-induced acute kidney injury	713:748	contrast-induced acute kidney injury (CI-AKI)	713:757	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	2	23	theme	posttranslational	412:428	arg1	modification					430:441	posttranslational modification	412:441	posttranslational modification	412:441	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	0	24	theme	Remote	0:5	arg1	Preconditioning					16:30	Remote Ischemic Preconditioning	0:30	Remote Ischemic Preconditioning	0:30	Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.
30186544	7	25	theme	apoptosis	1180:1188	arg1	species					1224:1230	reactive oxygen species	1208:1230	reactive oxygen species	1208:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	25	theme	apoptosis	1180:1188	arg1	presence					1144:1151	the presence	1140:1151	the presence of less tubular damage and apoptosis	1140:1188	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	25	theme	apoptosis	1180:1188	arg1	apoptosis					1180:1188	apoptosis	1180:1188	apoptosis	1180:1188	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	25	theme	apoptosis	1180:1188	arg1	amount					1198:1203	the amount	1194:1203	the amount of reactive oxygen species	1194:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	25	theme	apoptosis	1180:1188	arg1	damage					1169:1174	less tubular damage	1156:1174	less tubular damage	1156:1174	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	2	26	theme	protein	492:498	arg1	functions					500:508	multiple cytoplasmic and nuclear protein functions	459:508	multiple cytoplasmic and nuclear protein functions	459:508	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	6	27	theme	renal	1044:1048	arg1	O-GlcNAcylation					1050:1064	global renal O-GlcNAcylation	1037:1064	the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation	990:1064	We found that RIPC increased UDP-GlcNAc levels through the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation.
30186544	7	28	theme	tubular	1161:1167	arg1	damage					1169:1174	less tubular damage	1156:1174	less tubular damage	1156:1174	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	2	29	theme	β-N-acetylglucosamine	321:341	arg1	glycosylation					354:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation	312:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins	312:392	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	9	30	theme	contrast	1554:1561	arg1	exposure					1563:1570	contrast exposure	1554:1570	contrast exposure	1554:1570	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	8	31	theme	amidotransferase	1349:1364	arg1	azaserine					1305:1313	azaserine	1305:1313	azaserine	1305:1313	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	8	31	theme	amidotransferase	1349:1364	arg1	inhibitor					1366:1374	a glutamine fructose-6-phosphate amidotransferase inhibitor	1316:1374	a glutamine fructose-6-phosphate amidotransferase inhibitor	1316:1374	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	2	32	theme	nuclear	484:490	arg1	functions					500:508	multiple cytoplasmic and nuclear protein functions	459:508	multiple cytoplasmic and nuclear protein functions	459:508	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	6	33	theme	global	1037:1042	arg1	O-GlcNAcylation					1050:1064	global renal O-GlcNAcylation	1037:1064	the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation	990:1064	We found that RIPC increased UDP-GlcNAc levels through the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation.
30186544	7	34	theme	damage	1169:1174	arg1	species					1224:1230	reactive oxygen species	1208:1230	reactive oxygen species	1208:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	34	theme	damage	1169:1174	arg1	presence					1144:1151	the presence	1140:1151	the presence of less tubular damage and apoptosis	1140:1188	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	34	theme	damage	1169:1174	arg1	apoptosis					1180:1188	apoptosis	1180:1188	apoptosis	1180:1188	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	34	theme	damage	1169:1174	arg1	amount					1198:1203	the amount	1194:1203	the amount of reactive oxygen species	1194:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	34	theme	damage	1169:1174	arg1	damage					1169:1174	less tubular damage	1156:1174	less tubular damage	1156:1174	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	2	35	theme	O-linked	312:319	arg1	glycosylation					354:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation	312:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins	312:392	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	9	36	theme	useful	1642:1647	arg1	this					1616:1619	this	1616:1619	this	1616:1619	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	9	36	theme	useful	1642:1647	arg1	approach					1649:1656	a potentially useful approach	1628:1656	a potentially useful approach for lowering the risk of CI-AKI	1628:1688	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	2	37	theme	cytoplasmic	468:478	arg1	functions					500:508	multiple cytoplasmic and nuclear protein functions	459:508	multiple cytoplasmic and nuclear protein functions	459:508	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	0	38	theme	Kidney	50:55	arg1	Injury					57:62	Acute Kidney Injury	44:62	Acute Kidney Injury due to Contrast Exposure in Rats	44:95	Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.
30186544	4	39	theme	O-GlcNAc	773:780	arg1	signaling					782:790	O-GlcNAc signaling	773:790	O-GlcNAc signaling	773:790	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	2	40	theme	multiple	459:466	arg1	functions					500:508	multiple cytoplasmic and nuclear protein functions	459:508	multiple cytoplasmic and nuclear protein functions	459:508	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	1	41	theme	local	213:217	arg1	preconditioning					239:253	local short-term ischemic preconditioning	213:253	local short-term ischemic preconditioning	213:253	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	0	42	theme	Acute	44:48	arg1	Injury					57:62	Acute Kidney Injury	44:62	Acute Kidney Injury due to Contrast Exposure in Rats	44:95	Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.
30186544	4	43	theme	current	632:638	arg1	study					640:644	The current study	628:644	The current study	628:644	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	9	44	theme	glycosylation	1594:1606	arg1	levels					1608:1613	O-GlcNAc glycosylation levels	1585:1613	O-GlcNAc glycosylation levels	1585:1613	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	8	45	theme	O-GlcNAc	1269:1276	arg1	inhibitor					1290:1298	an O-GlcNAc transferase inhibitor	1266:1298	an O-GlcNAc transferase inhibitor	1266:1298	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	8	45	theme	O-GlcNAc	1269:1276	arg1	alloxan					1257:1263	alloxan	1257:1263	alloxan	1257:1263	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	1	46	theme	short-term	219:228	arg1	preconditioning					239:253	local short-term ischemic preconditioning	213:253	local short-term ischemic preconditioning	213:253	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	7	47	theme	species	1224:1230	arg1	species					1224:1230	reactive oxygen species	1208:1230	reactive oxygen species	1208:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	47	theme	species	1224:1230	arg1	presence					1144:1151	the presence	1140:1151	the presence of less tubular damage and apoptosis	1140:1188	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	47	theme	species	1224:1230	arg1	apoptosis					1180:1188	apoptosis	1180:1188	apoptosis	1180:1188	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	47	theme	species	1224:1230	arg1	amount					1198:1203	the amount	1194:1203	the amount of reactive oxygen species	1194:1230	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	7	47	theme	species	1224:1230	arg1	damage					1169:1174	less tubular damage	1156:1174	less tubular damage	1156:1174	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	2	48	link	O-linked	312:319	arg1	glycosylation					354:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation	312:366	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins	312:392	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	4	49	theme	contrast-induced	713:728	arg1	CI-AKI					751:756	CI-AKI	751:756	CI-AKI	751:756	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	4	49	theme	contrast-induced	713:728	arg1	injury					743:748	contrast-induced acute kidney injury	713:748	contrast-induced acute kidney injury (CI-AKI)	713:757	The current study aimed to determine whether RIPC can provide renoprotection against contrast-induced acute kidney injury (CI-AKI) by augmenting O-GlcNAc signaling.
30186544	9	50	theme	O-GlcNAc	1585:1592	arg1	levels					1608:1613	O-GlcNAc glycosylation levels	1585:1613	O-GlcNAc glycosylation levels	1585:1613	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	2	51	theme	intracellular	371:383	arg1	proteins					385:392	intracellular proteins	371:392	intracellular proteins	371:392	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	7	52	theme	O-GlcNAc	1093:1100	arg1	signaling					1102:1110	O-GlcNAc signaling	1093:1110	O-GlcNAc signaling	1093:1110	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	1	53	theme	Remote	132:137	arg1	response					186:193	an adaptive response	174:193	an adaptive response	174:193	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	1	53	theme	Remote	132:137	arg1	RIPC					165:168	RIPC	165:168	RIPC	165:168	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	1	53	theme	Remote	132:137	arg1	preconditioning					148:162	Remote ischemic preconditioning	132:162	Remote ischemic preconditioning (RIPC)	132:169	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	6	54	theme	biosynthetic	1005:1016	arg1	pathway					1018:1024	the hexosamine biosynthetic pathway	990:1024	the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation	990:1064	We found that RIPC increased UDP-GlcNAc levels through the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation.
30186544	7	55	theme	signaling	1102:1110	arg1	elevation					1080:1088	RIPC-induced elevation	1067:1088	RIPC-induced elevation of O-GlcNAc signaling	1067:1110	RIPC-induced elevation of O-GlcNAc signaling ameliorated CI-AKI based on the presence of less tubular damage and apoptosis and the amount of reactive oxygen species.
30186544	1	56	theme	ischemic	139:146	arg1	response					186:193	an adaptive response	174:193	an adaptive response	174:193	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	1	56	theme	ischemic	139:146	arg1	RIPC					165:168	RIPC	165:168	RIPC	165:168	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	1	56	theme	ischemic	139:146	arg1	preconditioning					148:162	Remote ischemic preconditioning	132:162	Remote ischemic preconditioning (RIPC)	132:169	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	9	57	theme	CI-AKI	1683:1688	arg1	risk					1675:1678	the risk	1671:1678	the risk of CI-AKI	1671:1688	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	1	58	theme	ischemic	230:237	arg1	preconditioning					239:253	local short-term ischemic preconditioning	213:253	local short-term ischemic preconditioning	213:253	Remote ischemic preconditioning (RIPC) is an adaptive response, manifesting when local short-term ischemic preconditioning reduces damage to adjacent or distant tissues or organs.
30186544	2	59	gly	glycosylation	354:366	arg1	proteins					385:392	intracellular proteins	371:392	intracellular proteins	371:392	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	8	60	theme	azaserine	1305:1313	arg1	use					1250:1252	the use	1246:1252	the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor,	1246:1375	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	8	61	theme	protective	1393:1402	arg1	effect					1404:1409	the protective effect	1389:1409	the protective effect of RIPC against oxidative stress and tubular apoptosis	1389:1464	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	8	62	theme	transferase	1278:1288	arg1	inhibitor					1290:1298	an O-GlcNAc transferase inhibitor	1266:1298	an O-GlcNAc transferase inhibitor	1266:1298	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	8	62	theme	transferase	1278:1288	arg1	alloxan					1257:1263	alloxan	1257:1263	alloxan	1257:1263	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	0	63	theme	Contrast	71:78	arg1	Exposure					80:87	Contrast Exposure	71:87	Contrast Exposure	71:87	Remote Ischemic Preconditioning Ameliorates Acute Kidney Injury due to Contrast Exposure in Rats through Augmented O-GlcNAcylation.
30186544	5	64	theme	tail	924:927	arg1	vein					929:932	the tail vein	920:932	the tail vein	920:932	We established a stable model of CI-AKI using 5/6 nephrectomized rats exposed to dehydration followed by iohexol injection via the tail vein.
30186544	3	65	theme	Growing	511:517	arg1	evidence					519:526	Growing evidence	511:526	Growing evidence	511:526	Growing evidence indicates that stress can induce an acute increase in O-GlcNAc levels, which can be cytoprotective.
30186544	8	66	theme	RIPC	1414:1417	arg1	effect					1404:1409	the protective effect	1389:1409	the protective effect of RIPC against oxidative stress and tubular apoptosis	1389:1464	In addition, the use of alloxan, an O-GlcNAc transferase inhibitor, and azaserine, a glutamine fructose-6-phosphate amidotransferase inhibitor, neutralized the protective effect of RIPC against oxidative stress and tubular apoptosis.
30186544	2	67	theme	modification	430:441	arg1	type					404:407	a type	402:407	a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions	402:508	O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation of intracellular proteins denotes a type of posttranslational modification that influences multiple cytoplasmic and nuclear protein functions.
30186544	9	68	theme	local	1498:1502	arg1	stress					1514:1519	local oxidative stress	1498:1519	local oxidative stress	1498:1519	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30186544	5	69	theme	CI-AKI	826:831	arg1	model					817:821	a stable model	808:821	a stable model of CI-AKI	808:831	We established a stable model of CI-AKI using 5/6 nephrectomized rats exposed to dehydration followed by iohexol injection via the tail vein.
30186544	6	70	theme	hexosamine	994:1003	arg1	pathway					1018:1024	the hexosamine biosynthetic pathway	990:1024	the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation	990:1064	We found that RIPC increased UDP-GlcNAc levels through the hexosamine biosynthetic pathway as well as global renal O-GlcNAcylation.
30186544	5	71	theme	iohexol	898:904	arg1	injection					906:914	iohexol injection	898:914	iohexol injection	898:914	We established a stable model of CI-AKI using 5/6 nephrectomized rats exposed to dehydration followed by iohexol injection via the tail vein.
30186544	3	72	theme	O-GlcNAc	582:589	arg1	levels					591:596	O-GlcNAc levels	582:596	O-GlcNAc levels	582:596	Growing evidence indicates that stress can induce an acute increase in O-GlcNAc levels, which can be cytoprotective.
30186544	9	73	theme	oxidative	1504:1512	arg1	stress					1514:1519	local oxidative stress	1498:1519	local oxidative stress	1498:1519	In conclusion, RIPC attenuates local oxidative stress and tubular apoptosis induced by contrast exposure by enhancing O-GlcNAc glycosylation levels; this can be a potentially useful approach for lowering the risk of CI-AKI.
30593635	4	0	theme	final	905:909	arg1	yields					911:916	final yields	905:916	final yields of eE2 approaching 60 mg/L of cell culture supernatant	905:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	5	1	theme	biophysical	1030:1040	arg1	studies					1042:1048	biophysical studies	1030:1048	biophysical studies	1030:1048	eE2 produced by this system is amenable to a variety of biophysical studies, including structural determination by X-ray crystallography.
30593635	1	2	theme	proper	158:163	arg1	folding					165:171	proper folding	158:171	proper folding	158:171	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	4	3	theme	supernatant	961:971	arg1	60 mg/L					937:943	60 mg/L	937:943	60 mg/L of cell culture supernatant	937:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	0	4	theme	Mammalian	79:87	arg1	Cells					89:93	Mammalian Cells	79:93	Mammalian Cells	79:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	0	5	from	Challenges	11:20	arg1	Cells					89:93	Mammalian Cells	79:93	Mammalian Cells	79:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	1	6	gly	glycoproteins	236:248	arg1	E2					266:267	E2	266:267	E2	266:267	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	6	gly	glycoproteins	236:248	arg1	E1					259:260	E1	259:260	E1	259:260	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	6	gly	glycoproteins	236:248	arg1	glycoproteins					236:248	the envelope glycoproteins 1 and 2	223:256	the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV)	223:295	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	2	7	theme	expression	312:321	arg1	yeast					349:353	yeast	349:353	yeast	349:353	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	7	theme	expression	312:321	arg1	systems					323:329	Commonly used expression systems	298:329	Commonly used expression systems such as bacteria, yeast, and baculovirus	298:370	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	7	theme	expression	312:321	arg1	bacteria					339:346	bacteria	339:346	bacteria	339:346	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	7	theme	expression	312:321	arg1	baculovirus					360:370	baculovirus	360:370	baculovirus	360:370	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	3	8	theme	E2	570:571	arg1	eE2					585:587	eE2	585:587	eE2	585:587	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	8	theme	E2	570:571	arg1	ectodomain					573:582	HCV E2 ectodomain	566:582	HCV E2 ectodomain (eE2)	566:588	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	4	9	theme	protein	860:866	arg1	expression					868:877	recombinant protein expression	848:877	recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	848:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	3	10	theme	N-linked	598:605	arg1	glycans					607:613	11 N-linked glycans	595:613	11 N-linked glycans	595:613	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	11	theme	adherent	725:732	arg1	growth					717:722	a continuous growth	704:722	a continuous growth	704:722	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	11	theme	adherent	725:732	arg1	bioreactor					739:748	adherent cell bioreactor	725:748	adherent cell bioreactor	725:748	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	2	12	theme	molecular	454:462	arg1	machinery					464:472	molecular machinery	454:472	molecular machinery necessary for PTMs	454:491	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	3	13	theme	cell	734:737	arg1	growth					717:722	a continuous growth	704:722	a continuous growth	704:722	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	13	theme	cell	734:737	arg1	bioreactor					739:748	adherent cell bioreactor	725:748	adherent cell bioreactor	725:748	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	14	theme	cells	694:698	arg1	growth					717:722	a continuous growth	704:722	a continuous growth	704:722	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	14	theme	cells	694:698	arg1	transduction					668:679	lentivirus transduction	657:679	lentivirus transduction of mammalian cells	657:698	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	14	theme	cells	694:698	arg1	bioreactor					739:748	adherent cell bioreactor	725:748	adherent cell bioreactor	725:748	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	4	15	theme	expression	868:877	arg1	methods					837:843	other methods	831:843	other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	831:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	6	16	theme	cell	1259:1262	arg1	lines					1264:1268	mammalian cell lines	1249:1268	mammalian cell lines	1249:1268	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	1	17	theme	physiological	177:189	arg1	function					191:198	physiological function	177:198	physiological function	177:198	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	0	18	from	Production	65:74	arg1	Cells					89:93	Mammalian Cells	79:93	Mammalian Cells	79:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	3	19	theme	disulfide	625:633	arg1	bonds					635:639	eight disulfide bonds	619:639	eight disulfide bonds	619:639	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	5	20	theme	X-ray	1089:1093	arg1	crystallography					1095:1109	X-ray crystallography	1089:1109	X-ray crystallography	1089:1109	eE2 produced by this system is amenable to a variety of biophysical studies, including structural determination by X-ray crystallography.
30593635	6	21	theme	target	1217:1222	arg1	proteins					1224:1231	difficult target proteins	1207:1231	difficult target proteins	1207:1231	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	5	22	theme	studies	1042:1048	arg1	determination					1072:1084	structural determination	1061:1084	structural determination by X-ray crystallography	1061:1109	eE2 produced by this system is amenable to a variety of biophysical studies, including structural determination by X-ray crystallography.
30593635	5	22	theme	studies	1042:1048	arg1	variety					1019:1025	a variety	1017:1025	a variety	1017:1025	eE2 produced by this system is amenable to a variety of biophysical studies, including structural determination by X-ray crystallography.
30593635	5	22	theme	studies	1042:1048	arg1	studies					1042:1048	biophysical studies	1030:1048	biophysical studies	1030:1048	eE2 produced by this system is amenable to a variety of biophysical studies, including structural determination by X-ray crystallography.
30593635	3	23	theme	lentivirus	657:666	arg1	transduction					668:679	lentivirus transduction	657:679	lentivirus transduction of mammalian cells	657:698	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	4	24	theme	environmentally	757:771	arg1	friendly					773:780	environmentally friendly	757:780	environmentally friendly	757:780	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	1	25	theme	Posttranslational	96:112	arg1	PTMs					129:132	PTMs	129:132	PTMs	129:132	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	25	theme	Posttranslational	96:112	arg1	modifications					114:126	Posttranslational modifications	96:126	Posttranslational modifications (PTMs)	96:133	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	0	26	theme	Hepatitis	25:33	arg1	Glycoprotein					52:63	Hepatitis C Virus Envelope Glycoprotein	25:63	Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells	25:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	4	27	theme	other	831:835	arg1	methods					837:843	other methods	831:843	other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	831:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	3	28	link	N-linked	598:605	arg1	glycans					607:613	11 N-linked glycans	595:613	11 N-linked glycans	595:613	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	1	29	theme	proteins	203:210	arg1	function					191:198	physiological function	177:198	physiological function	177:198	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	29	theme	proteins	203:210	arg1	folding					165:171	proper folding	158:171	proper folding	158:171	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	2	30	theme	HCV	388:390	arg1	E2					399:400	E2	399:400	E2	399:400	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	30	theme	HCV	388:390	arg1	E1					392:393	soluble HCV E1	380:393	soluble HCV E1	380:393	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	30	theme	HCV	388:390	arg1	environment					438:448	the cellular environment	425:448	the cellular environment	425:448	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	4	31	theme	eE2	921:923	arg1	yields					911:916	final yields	905:916	final yields of eE2 approaching 60 mg/L of cell culture supernatant	905:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	0	32	from	Cells	89:93	arg1	Challenges					11:20	Challenges	11:20	Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells	11:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	0	33	theme	Virus	37:41	arg1	Glycoprotein					52:63	Hepatitis C Virus Envelope Glycoprotein	25:63	Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells	25:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	1	34	theme	hepatitis	273:281	arg1	virus					285:289	hepatitis C virus	273:289	hepatitis C virus (HCV)	273:295	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	34	theme	hepatitis	273:281	arg1	HCV					292:294	HCV	292:294	HCV	292:294	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	4	35	theme	recombinant	848:858	arg1	expression					868:877	recombinant protein expression	848:877	recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	848:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	4	36	from	methods	837:843	arg1	systems					892:898	mammalian systems	882:898	mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	882:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	3	37	with	ectodomain	573:582	arg1	glycans					607:613	11 N-linked glycans	595:613	11 N-linked glycans	595:613	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	37	with	ectodomain	573:582	arg1	bonds					635:639	eight disulfide bonds	619:639	eight disulfide bonds	619:639	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	4	38	from	expression	868:877	arg1	systems					892:898	mammalian systems	882:898	mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	882:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	0	39	theme	C	35:35	arg1	Glycoprotein					52:63	Hepatitis C Virus Envelope Glycoprotein	25:63	Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells	25:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	1	40	theme	C	283:283	arg1	virus					285:289	hepatitis C virus	273:289	hepatitis C virus (HCV)	273:295	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	40	theme	C	283:283	arg1	HCV					292:294	HCV	292:294	HCV	292:294	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	2	41	theme	low	410:412	arg1	yields					414:419	very low yields	405:419	very low yields	405:419	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	4	42	theme	culture	953:959	arg1	supernatant					961:971	cell culture supernatant	948:971	cell culture supernatant	948:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	2	43	theme	necessary	474:482	arg1	machinery					464:472	molecular machinery	454:472	molecular machinery necessary for PTMs	454:491	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	6	44	theme	mammalian	1249:1257	arg1	lines					1264:1268	mammalian cell lines	1249:1268	mammalian cell lines	1249:1268	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	0	45	theme	Glycoprotein	52:63	arg1	Production					65:74	Hepatitis C Virus Envelope Glycoprotein Production	25:74	Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells	25:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	1	46	theme	virus	285:289	arg1	E2					266:267	E2	266:267	E2	266:267	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	46	theme	virus	285:289	arg1	E1					259:260	E1	259:260	E1	259:260	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	46	theme	virus	285:289	arg1	glycoproteins					236:248	the envelope glycoproteins 1 and 2	223:256	the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV)	223:295	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	6	47	theme	proteins	1224:1231	arg1	array					1198:1202	an array	1195:1202	an array of difficult target proteins	1195:1231	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	1	48	dep	glycoproteins	236:248	arg1	1					250:250	1	250:250	1	250:250	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	48	dep	glycoproteins	236:248	arg1	E2					266:267	E2	266:267	E2	266:267	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	48	dep	glycoproteins	236:248	arg1	E1					259:260	E1	259:260	E1	259:260	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	48	dep	glycoproteins	236:248	arg1	glycoproteins					236:248	the envelope glycoproteins 1 and 2	223:256	the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV)	223:295	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	48	dep	glycoproteins	236:248	arg1	2					256:256	2	256:256	2	256:256	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	6	49	theme	flexibility	1144:1154	arg1	ease					1128:1131	the ease	1124:1131	the ease of use and flexibility	1124:1154	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	2	50	theme	used	307:310	arg1	yeast					349:353	yeast	349:353	yeast	349:353	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	50	theme	used	307:310	arg1	systems					323:329	Commonly used expression systems	298:329	Commonly used expression systems such as bacteria, yeast, and baculovirus	298:370	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	50	theme	used	307:310	arg1	bacteria					339:346	bacteria	339:346	bacteria	339:346	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	50	theme	used	307:310	arg1	baculovirus					360:370	baculovirus	360:370	baculovirus	360:370	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	0	51	theme	Envelope	43:50	arg1	Glycoprotein					52:63	Hepatitis C Virus Envelope Glycoprotein	25:63	Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells	25:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	4	52	theme	cost-	794:798	arg1	friendly					773:780	environmentally friendly	757:780	environmentally friendly	757:780	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	3	53	theme	HCV	566:568	arg1	eE2					585:587	eE2	585:587	eE2	585:587	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	53	theme	HCV	566:568	arg1	ectodomain					573:582	HCV E2 ectodomain	566:582	HCV E2 ectodomain (eE2)	566:588	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	4	54	theme	mammalian	882:890	arg1	systems					892:898	mammalian systems	882:898	mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	882:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	4	55	with	systems	892:898	arg1	yields					911:916	final yields	905:916	final yields of eE2 approaching 60 mg/L of cell culture supernatant	905:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	3	56	theme	mammalian	684:692	arg1	cells					694:698	mammalian cells	684:698	mammalian cells	684:698	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	6	57	theme	difficult	1207:1215	arg1	proteins					1224:1231	difficult target proteins	1207:1231	difficult target proteins	1207:1231	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	6	58	theme	use	1136:1138	arg1	ease					1128:1131	the ease	1124:1131	the ease of use and flexibility	1124:1154	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	3	59	theme	expression	544:553	arg1	system					555:560	an expression system	541:560	an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor	541:748	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	1	60	theme	envelope	227:234	arg1	E2					266:267	E2	266:267	E2	266:267	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	60	theme	envelope	227:234	arg1	E1					259:260	E1	259:260	E1	259:260	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	1	60	theme	envelope	227:234	arg1	glycoproteins					236:248	the envelope glycoproteins 1 and 2	223:256	the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV)	223:295	Posttranslational modifications (PTMs) are often required for proper folding and physiological function of proteins, including the envelope glycoproteins 1 and 2 (E1 and E2) of hepatitis C virus (HCV).
30593635	4	61	theme	time-efficient	804:817	arg1	friendly					773:780	environmentally friendly	757:780	environmentally friendly	757:780	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	6	62	theme	lines	1264:1268	arg1	lines					1264:1268	mammalian cell lines	1249:1268	mammalian cell lines	1249:1268	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	6	62	theme	lines	1264:1268	arg1	variety					1238:1244	a variety	1236:1244	a variety of mammalian cell lines	1236:1268	Considering the ease of use and flexibility, this method can be applied to express an array of difficult target proteins in a variety of mammalian cell lines.
30593635	2	63	theme	cellular	429:436	arg1	E2					399:400	E2	399:400	E2	399:400	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	63	theme	cellular	429:436	arg1	E1					392:393	soluble HCV E1	380:393	soluble HCV E1	380:393	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	63	theme	cellular	429:436	arg1	environment					438:448	the cellular environment	425:448	the cellular environment	425:448	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	64	theme	soluble	380:386	arg1	E2					399:400	E2	399:400	E2	399:400	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	64	theme	soluble	380:386	arg1	E1					392:393	soluble HCV E1	380:393	soluble HCV E1	380:393	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	2	64	theme	soluble	380:386	arg1	environment					438:448	the cellular environment	425:448	the cellular environment	425:448	Commonly used expression systems such as bacteria, yeast, and baculovirus produce soluble HCV E1 and E2 at very low yields, as the cellular environment and molecular machinery necessary for PTMs may be suboptimal or missing.
30593635	4	65	from	systems	892:898	arg1	methods					837:843	other methods	831:843	other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant	831:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	0	66	theme	Production	65:74	arg1	Challenges					11:20	Challenges	11:20	Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells	11:93	Overcoming Challenges of Hepatitis C Virus Envelope Glycoprotein Production in Mammalian Cells.
30593635	5	67	theme	structural	1061:1070	arg1	determination					1072:1084	structural determination	1061:1084	structural determination by X-ray crystallography	1061:1109	eE2 produced by this system is amenable to a variety of biophysical studies, including structural determination by X-ray crystallography.
30593635	4	68	theme	cell	948:951	arg1	supernatant					961:971	cell culture supernatant	948:971	cell culture supernatant	948:971	It is environmentally friendly, as well as cost- and time-efficient compared to other methods of recombinant protein expression in mammalian systems with final yields of eE2 approaching 60 mg/L of cell culture supernatant.
30593635	3	69	theme	continuous	706:715	arg1	growth					717:722	a continuous growth	704:722	a continuous growth	704:722	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30593635	3	69	theme	continuous	706:715	arg1	bioreactor					739:748	adherent cell bioreactor	725:748	adherent cell bioreactor	725:748	Here, we describe an expression system for HCV E2 ectodomain (eE2) with 11 N-linked glycans and eight disulfide bonds, which combines lentivirus transduction of mammalian cells and a continuous growth, adherent cell bioreactor.
30178920	0	0	theme	Glycopeptides	103:115	arg1	Enrichment					89:98	Selective Enrichment	79:98	Selective Enrichment of Glycopeptides and Glycans	79:127	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	2	1	theme	monolithic	575:584	arg1	material					586:593	the monolithic material	571:593	the monolithic material	571:593	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	1	2	theme	methacrylate-ethyleneglycol	159:185	arg1	poly					145:148	poly	145:148	poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid	145:273	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	1	2	theme	methacrylate-ethyleneglycol	159:185	arg1	dimethacrylate					187:200	glycidyl methacrylate-ethyleneglycol dimethacrylate	150:200	glycidyl methacrylate-ethyleneglycol dimethacrylate	150:200	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	4	3	dep	IgG	978:980	arg1	50:1					983:986	50:1	983:986	50:1	983:986	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	4	3	dep	IgG	978:980	arg1	m/m					989:991	m/m	989:991	m/m	989:991	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	6	4	theme	serum	1335:1339	arg1	samples					1341:1347	human serum samples	1329:1347	human serum samples	1329:1347	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	2	5	theme	cobalt	407:412	arg1	phthalocyanine					414:427	cobalt phthalocyanine	407:427	cobalt phthalocyanine	407:427	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	6	6	from	enrichment	1295:1304	arg1	samples					1341:1347	human serum samples	1329:1347	human serum samples	1329:1347	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	0	7	theme	Glycans	121:127	arg1	Enrichment					89:98	Selective Enrichment	79:98	Selective Enrichment of Glycopeptides and Glycans	79:127	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	3	8	gly	glycopeptides	861:873	arg2	glycopeptides					861:873	only four and three glycopeptides	841:873	only four and three glycopeptides	841:873	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	6	9	theme	human	1329:1333	arg1	samples					1341:1347	human serum samples	1329:1347	human serum samples	1329:1347	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	3	10	with	enrichment	811:820	arg1	monolith					831:838	the monolith	827:838	the monolith	827:838	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	4	11	gly	glycopeptides	1041:1053	arg2	glycopeptides					1041:1053	glycopeptides	1041:1053	glycopeptides	1041:1053	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	2	12	theme	glycopeptides	332:344	arg1	enrichment					346:355	glycopeptides enrichment	332:355	glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively	332:680	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	3	13	gly	glycoproteins	733:745	arg1	glycoproteins					733:745	the model glycoproteins	723:745	the model glycoproteins	723:745	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	6	14	theme	glycoproteins	1404:1416	arg1	analysis					1392:1399	the analysis	1388:1399	the analysis of glycoproteins	1388:1416	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	6	15	theme	N-linked	1309:1316	arg1	glycans					1318:1324	N-linked glycans	1309:1324	N-linked glycans	1309:1324	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	6	16	theme	glycans	1318:1324	arg1	enrichment					1295:1304	the enrichment	1291:1304	the enrichment of N-linked glycans in human serum samples	1291:1347	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	3	17	dep	IgG	688:690	arg1	identified					781:790	identified	781:790	could be identified respectively after enrichment with the monolith	772:838	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	4	18	theme	enrichment	1015:1024	arg1	selectivity					1026:1036	the high enrichment selectivity	1006:1036	the high enrichment selectivity of glycopeptides	1006:1053	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	4	19	theme	interference	1087:1098	arg1	ratio					1100:1104	a large interference ratio	1079:1104	a large interference ratio	1079:1104	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	4	20	theme	large	1081:1085	arg1	ratio					1100:1104	a large interference ratio	1079:1104	a large interference ratio	1079:1104	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	2	21	theme	isoindole	462:470	arg1	subunits					472:479	isoindole subunits	462:479	isoindole subunits of phthalocyanine and glycans	462:509	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	0	22	theme	Phthalocyanine	7:20	arg1	Monolith					66:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith	0:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.	0:128	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	4	23	theme	digests	951:957	arg1	mixture					959:965	the digests mixture	947:965	the digests mixture of BSA and IgG (50:1, m/m)	947:992	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	4	24	theme	high	1010:1013	arg1	selectivity					1026:1036	the high enrichment selectivity	1006:1036	the high enrichment selectivity of glycopeptides	1006:1053	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	0	25	theme	Cobalt	0:5	arg1	Monolith					66:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith	0:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.	0:128	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	2	26	gly	glycopeptides	640:652	arg2	glycopeptides					640:652	glycopeptides	640:652	glycopeptides	640:652	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	0	27	theme	Acid	38:41	arg1	Monolith					66:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith	0:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.	0:128	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	6	28	gly	glycoproteins	1404:1416	arg1	glycoproteins					1404:1416	glycoproteins	1404:1416	glycoproteins	1404:1416	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	3	29	theme	horse	696:700	arg1	peroxidase					709:718	horse radish peroxidase	696:718	horse radish peroxidase	696:718	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	1	30	theme	cobalt	232:237	arg1	acid					270:273	cobalt phthalocyanine tetracarboxylic acid	232:273	cobalt phthalocyanine tetracarboxylic acid	232:273	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	0	31	theme	Tetracarboxylic	22:36	arg1	Monolith					66:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith	0:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.	0:128	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	2	32	theme	glycopeptides	640:652	arg1	enrichment					626:635	the enrichment	622:635	the enrichment of glycopeptides	622:652	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	1	33	theme	phthalocyanine	239:252	arg1	acid					270:273	cobalt phthalocyanine tetracarboxylic acid	232:273	cobalt phthalocyanine tetracarboxylic acid	232:273	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	0	34	theme	Polymer	58:64	arg1	Monolith					66:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith	0:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.	0:128	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	2	35	theme	phthalocyanine	484:497	arg1	subunits					472:479	isoindole subunits	462:479	isoindole subunits of phthalocyanine and glycans	462:509	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	2	36	gly	glycopeptides	556:568	arg2	glycopeptides					556:568	glycopeptides	556:568	glycopeptides	556:568	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	6	37	link	N-linked	1309:1316	arg1	glycans					1318:1324	N-linked glycans	1309:1324	N-linked glycans	1309:1324	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	1	38	theme	tetracarboxylic	254:268	arg1	acid					270:273	cobalt phthalocyanine tetracarboxylic acid	232:273	cobalt phthalocyanine tetracarboxylic acid	232:273	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	0	39	theme	Functionalized	43:56	arg1	Monolith					66:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith	0:73	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.	0:128	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	2	40	theme	phthalocyanine	414:427	arg1	advantage					394:402	advantage	394:402	advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides	394:568	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	2	41	theme	coordination	512:523	arg1	interaction					525:535	coordination interaction	512:535	coordination interaction between cobalt	512:550	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	2	42	gly	glycopeptides	332:344	arg2	glycopeptides					332:344	glycopeptides enrichment	332:355	glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively	332:680	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	6	43	theme	great	1368:1372	arg1	potential					1374:1382	its great potential	1364:1382	its great potential for the analysis of glycoproteins	1364:1416	In addition, the monolith was successfully applied to the enrichment of N-linked glycans in human serum samples, demonstrating its great potential for the analysis of glycoproteins.
30178920	5	44	contain	had	1190:1192	arg1	method					1183:1188	the present method	1171:1188	the present method	1171:1188	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	5	44	contain	had	1190:1192	arg2	potential					1200:1208	great potential	1194:1208	great potential for trace sample analysis	1194:1234	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	5	45	theme	great	1194:1198	arg1	potential					1200:1208	great potential	1194:1208	great potential for trace sample analysis	1194:1234	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	5	46	theme	trace	1214:1218	arg1	analysis					1227:1234	trace sample analysis	1214:1234	trace sample analysis	1214:1234	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	4	47	theme	IgG	978:980	arg1	mixture					959:965	the digests mixture	947:965	the digests mixture of BSA and IgG (50:1, m/m)	947:992	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	4	48	dep	ratio	1100:1104	arg1	the					1063:1065	the	1063:1065	the	1063:1065	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	4	48	dep	ratio	1100:1104	arg1	presence					1067:1074	presence	1067:1074	presence	1067:1074	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	5	49	theme	sample	1220:1225	arg1	analysis					1227:1234	trace sample analysis	1214:1234	trace sample analysis	1214:1234	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	5	50	theme	detection	1111:1119	arg1	limit					1121:1125	The detection limit	1107:1125	The detection limit	1107:1125	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	5	50	theme	detection	1111:1119	arg1	6.7 fmol					1147:1154	6.7 fmol	1147:1154	6.7 fmol	1147:1154	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	3	51	theme	radish	702:707	arg1	peroxidase					709:718	horse radish peroxidase	696:718	horse radish peroxidase	696:718	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	3	52	theme	model	727:731	arg1	glycoproteins					733:745	the model glycoproteins	723:745	the model glycoproteins	723:745	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	1	53	theme	poly	145:148	arg1	monolith					203:210	poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith	145:210	poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid	145:273	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	4	54	theme	BSA	970:972	arg1	mixture					959:965	the digests mixture	947:965	the digests mixture of BSA and IgG (50:1, m/m)	947:992	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	4	55	theme	glycopeptides	1041:1053	arg1	selectivity					1026:1036	the high enrichment selectivity	1006:1036	the high enrichment selectivity of glycopeptides	1006:1053	The monolith is also employed to the digests mixture of BSA and IgG (50:1, m/m), indicating the high enrichment selectivity of glycopeptides even in the presence of a large interference ratio.
30178920	2	56	theme	monolithic	300:309	arg1	material					311:318	The polymer monolithic material	288:318	The polymer monolithic material	288:318	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	2	57	theme	glycans	503:509	arg1	subunits					472:479	isoindole subunits	462:479	isoindole subunits of phthalocyanine and glycans	462:509	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	2	58	theme	hydrogen	439:446	arg1	bonds					448:452	hydrogen bonds	439:452	hydrogen bonds between isoindole subunits of phthalocyanine and glycans	439:509	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	3	59	gly	glycopeptides	758:770	arg2	glycopeptides					758:770	17 glycopeptides	755:770	17 glycopeptides	755:770	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
30178920	0	60	theme	Selective	79:87	arg1	Enrichment					89:98	Selective Enrichment	79:98	Selective Enrichment of Glycopeptides and Glycans	79:127	Cobalt Phthalocyanine Tetracarboxylic Acid Functionalized Polymer Monolith for Selective Enrichment of Glycopeptides and Glycans.
30178920	5	61	theme	present	1175:1181	arg1	method					1183:1188	the present method	1171:1188	the present method	1171:1188	The detection limit is determined to be 6.7 fmol, implying that the present method had great potential for trace sample analysis.
30178920	2	62	theme	polymer	292:298	arg1	material					311:318	The polymer monolithic material	288:318	The polymer monolithic material	288:318	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	1	63	theme	glycidyl	150:157	arg1	poly					145:148	poly	145:148	poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid	145:273	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	1	63	theme	glycidyl	150:157	arg1	dimethacrylate					187:200	glycidyl methacrylate-ethyleneglycol dimethacrylate	150:200	glycidyl methacrylate-ethyleneglycol dimethacrylate	150:200	In this study, poly(glycidyl methacrylate-ethyleneglycol dimethacrylate) monolith functionalized with cobalt phthalocyanine tetracarboxylic acid is prepared.
30178920	2	64	used	used	323:326	arg2	material					311:318	The polymer monolithic material	288:318	The polymer monolithic material	288:318	The polymer monolithic material is used for glycopeptides enrichment coupled with MALDI-TOF MS. By taking advantage of cobalt phthalocyanine including hydrogen bonds between isoindole subunits of phthalocyanine and glycans, coordination interaction between cobalt and glycopeptides, the monolithic material is successfully applied to the enrichment of glycopeptides efficiently and selectively.
30178920	3	65	theme	direct	897:902	arg1	analysis					904:911	direct analysis	897:911	direct analysis	897:911	With IgG and horse radish peroxidase as the model glycoproteins, 28 and 17 glycopeptides could be identified respectively after enrichment with the monolith, only four and three glycopeptides could be obtained for direct analysis.
29790113	0	0	theme	Collision-Induced	82:98	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	0	theme	Collision-Induced	82:98	arg1	Fragmentation					100:112	Collision-Induced Fragmentation	82:112	Collision-Induced Fragmentation of Negative Ions	82:129	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	2	1	theme	fucose	536:541	arg1	residues					543:550	multiple fucose residues	527:550	multiple fucose residues forming the Lewisx and Lewisy epitopes	527:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	4	2	theme	branching	907:915	arg1	pattern					917:923	the branching pattern	903:923	the branching pattern of the triantennary glycans	903:951	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	4	3	theme	intact	756:761	arg1	N-glycans					763:771	the intact N-glycans	752:771	the intact N-glycans	752:771	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	4	4	theme	triantennary	932:943	arg1	glycans					945:951	the triantennary glycans	928:951	the triantennary glycans	928:951	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	2	5	theme	multiple	527:534	arg1	residues					543:550	multiple fucose residues	527:550	multiple fucose residues forming the Lewisx and Lewisy epitopes	527:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	2	6	from	information	484:494	arg1	glycans					508:514	N-linked glycans	499:514	N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes	499:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	1	7	theme	gas-phase	262:270	arg1	attributes					283:292	the gas-phase separation attributes	258:292	the gas-phase separation attributes not typically observed by orthogonal methods	258:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	2	8	theme	Lewisy	575:580	arg1	epitopes					582:589	the Lewisx and Lewisy epitopes	560:589	the Lewisx and Lewisy epitopes	560:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	1	9	from	use	172:174	arg1	glycobiology					224:235	structural glycobiology	213:235	structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods	213:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	6	10	theme	fragment	1083:1090	arg1	ions					1092:1095	Some isobaric fragment ions	1069:1095	Some isobaric fragment ions produced prior to ion mobility	1069:1126	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	1	11	theme	separation	272:281	arg1	attributes					283:292	the gas-phase separation attributes	258:292	the gas-phase separation attributes not typically observed by orthogonal methods	258:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	7	12	theme	Graphical	1277:1285	arg1	abstract					1287:1294	Graphical abstract	1277:1294	Graphical abstract	1277:1294	Graphical abstract ᅟ.
29790113	4	13	theme	negative	776:783	arg1	CID					789:791	negative ion CID	776:791	negative ion CID	776:791	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	0	14	theme	Ions	126:129	arg1	Spectrometry					65:76	Ion Mobility Mass Spectrometry	47:76	Ion Mobility Mass Spectrometry	47:76	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	14	theme	Ions	126:129	arg1	Fragmentation					100:112	Collision-Induced Fragmentation	82:112	Collision-Induced Fragmentation of Negative Ions	82:129	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	14	theme	Ions	126:129	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	4	15	theme	GlcNAc	884:889	arg1	residue					891:897	a bisecting GlcNAc residue	872:897	a bisecting GlcNAc residue	872:897	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	2	16	theme	collision-induced	431:447	arg1	dissociation					449:460	negative ion collision-induced dissociation	418:460	negative ion collision-induced dissociation	418:460	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	4	17	theme	glycan	830:835	arg1	pattern					917:923	the branching pattern	903:923	the branching pattern of the triantennary glycans	903:951	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	4	17	theme	glycan	830:835	arg1	topology					814:821	the general topology	802:821	the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue	802:897	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	2	18	theme	mobility	395:402	arg1	capability					362:371	the capability	358:371	the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes	358:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	4	19	dep	presence	849:856	arg1	the					845:847	the	845:847	the	845:847	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	0	20	theme	Negative	117:124	arg1	Ions					126:129	Negative Ions	117:129	Negative Ions	117:129	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	4	21	theme	bisecting	874:882	arg1	residue					891:897	a bisecting GlcNAc residue	872:897	a bisecting GlcNAc residue	872:897	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	2	22	link	N-linked	499:506	arg1	glycans					508:514	N-linked glycans	499:514	N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes	499:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	2	23	theme	structural	473:482	arg1	information					484:494	structural information	473:494	structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes	473:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	1	24	theme	ion	179:181	arg1	spectrometry					197:208	ion mobility mass spectrometry	179:208	ion mobility mass spectrometry	179:208	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	6	25	theme	isobaric	1074:1081	arg1	ions					1092:1095	Some isobaric fragment ions	1069:1095	Some isobaric fragment ions produced prior to ion mobility	1069:1126	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	6	26	theme	additional	1189:1198	arg1	information					1220:1230	additional valuable structural information	1189:1230	additional valuable structural information that was missing from the CID spectra alone	1189:1274	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	5	27	from	ions	1038:1041	arg1	obtainable					1022:1031	obtainable	1022:1031	obtainable	1022:1031	Information on the location of the fucose residues was also readily obtainable from ions specific to each antenna.
29790113	1	28	theme	mobility mass	183:195	arg1	spectrometry					197:208	ion mobility mass spectrometry	179:208	ion mobility mass spectrometry	179:208	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	0	29	theme	Structural	0:9	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	29	theme	Structural	0:9	arg1	Fragmentation					100:112	Collision-Induced Fragmentation	82:112	Collision-Induced Fragmentation of Negative Ions	82:129	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	29	theme	Structural	0:9	arg1	Spectrometry					65:76	Ion Mobility Mass Spectrometry	47:76	Ion Mobility Mass Spectrometry	47:76	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	4	30	theme	residue	891:897	arg1	absence					861:867	absence	861:867	absence	861:867	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	4	30	theme	residue	891:897	arg1	presence					849:856	presence	849:856	presence	849:856	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	5	31	from	Information	954:964	arg1	location					973:980	the location	969:980	the location of the fucose residues	969:1003	Information on the location of the fucose residues was also readily obtainable from ions specific to each antenna.
29790113	1	32	theme	spectrometry	197:208	arg1	use					172:174	the use	168:174	the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods	168:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	0	33	theme	Fucosylated	22:32	arg1	N-Glycans					34:42	Fucosylated N-Glycans	22:42	Fucosylated N-Glycans	22:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	5	34	theme	specific	1043:1050	arg1	ions					1038:1041	ions	1038:1041	ions specific to each antenna	1038:1066	Information on the location of the fucose residues was also readily obtainable from ions specific to each antenna.
29790113	2	35	contain	containing	516:525	arg1	glycans					508:514	N-linked glycans	499:514	N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes	499:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	2	35	contain	containing	516:525	arg2	residues					543:550	multiple fucose residues	527:550	multiple fucose residues forming the Lewisx and Lewisy epitopes	527:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	4	36	theme	general	806:812	arg1	topology					814:821	the general topology	802:821	the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue	802:897	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	6	37	theme	structural	1209:1218	arg1	information					1220:1230	additional valuable structural information	1189:1230	additional valuable structural information that was missing from the CID spectra alone	1189:1274	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	5	38	theme	residues	996:1003	arg1	location					973:980	the location	969:980	the location of the fucose residues	969:1003	Information on the location of the fucose residues was also readily obtainable from ions specific to each antenna.
29790113	2	39	theme	N-linked	499:506	arg1	glycans					508:514	N-linked glycans	499:514	N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes	499:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	1	40	theme	structural	213:222	arg1	glycobiology					224:235	structural glycobiology	213:235	structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods	213:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	4	41	theme	Specific	703:710	arg1	information					712:722	Specific information	703:722	Specific information that could be obtained from the intact N-glycans by negative ion CID	703:791	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	3	42	theme	cell-cell	641:649	arg1	recognition					651:661	cell-cell recognition	641:661	cell-cell recognition	641:661	These epitopes are involved in processes such as cell-cell recognition and are important as cancer biomarkers.
29790113	2	43	theme	ion	391:393	arg1	mobility					395:402	traveling wave ion mobility	376:402	traveling wave ion mobility combined with negative ion collision-induced dissociation	376:460	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	2	44	theme	ion	427:429	arg1	dissociation					449:460	negative ion collision-induced dissociation	418:460	negative ion collision-induced dissociation	418:460	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	0	45	theme	N-Glycans	34:42	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	45	theme	N-Glycans	34:42	arg1	Fragmentation					100:112	Collision-Induced Fragmentation	82:112	Collision-Induced Fragmentation of Negative Ions	82:129	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	45	theme	N-Glycans	34:42	arg1	Spectrometry					65:76	Ion Mobility Mass Spectrometry	47:76	Ion Mobility Mass Spectrometry	47:76	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	1	46	theme	orthogonal	320:329	arg1	methods					331:337	orthogonal methods	320:337	orthogonal methods	320:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	3	47	theme	cancer	684:689	arg1	biomarkers					691:700	cancer biomarkers	684:700	cancer biomarkers	684:700	These epitopes are involved in processes such as cell-cell recognition and are important as cancer biomarkers.
29790113	1	48	theme	due	237:239	arg1	glycobiology					224:235	structural glycobiology	213:235	structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods	213:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	0	49	theme	Mobility	51:58	arg1	Spectrometry					65:76	Ion Mobility Mass Spectrometry	47:76	Ion Mobility Mass Spectrometry	47:76	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	49	theme	Mobility	51:58	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	1	50	from	part	250:253	arg1	due					237:239	due	237:239	due	237:239	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	6	51	dep	separated	1150:1158	arg1	provided					1180:1187	provided	1180:1187	provided additional valuable structural information that was missing from the CID spectra alone	1180:1274	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	1	52	from	due	237:239	arg1	part					250:253	large part	244:253	large part to the gas-phase separation attributes not typically observed by orthogonal methods	244:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	0	53	theme	Ion	47:49	arg1	Spectrometry					65:76	Ion Mobility Mass Spectrometry	47:76	Ion Mobility Mass Spectrometry	47:76	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	53	theme	Ion	47:49	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	6	54	theme	CID	1258:1260	arg1	spectra					1262:1268	the CID spectra	1254:1268	the CID spectra alone	1254:1274	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	6	55	from	spectra	1262:1268	arg1	missing					1241:1247	missing	1241:1247	missing	1241:1247	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	4	56	theme	ion	785:787	arg1	CID					789:791	negative ion CID	776:791	negative ion CID	776:791	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	5	57	theme	fucose	989:994	arg1	residues					996:1003	the fucose residues	985:1003	the fucose residues	985:1003	Information on the location of the fucose residues was also readily obtainable from ions specific to each antenna.
29790113	4	58	theme	glycans	945:951	arg1	pattern					917:923	the branching pattern	903:923	the branching pattern of the triantennary glycans	903:951	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	4	58	theme	glycans	945:951	arg1	topology					814:821	the general topology	802:821	the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue	802:897	Specific information that could be obtained from the intact N-glycans by negative ion CID included the general topology of the glycan such as the presence or absence of a bisecting GlcNAc residue and the branching pattern of the triantennary glycans.
29790113	1	59	theme	considerable	141:152	arg1	potential					154:162	considerable potential	141:162	considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods	141:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	1	60	theme	large	244:248	arg1	part					250:253	large part	244:253	large part to the gas-phase separation attributes not typically observed by orthogonal methods	244:337	There is considerable potential for the use of ion mobility mass spectrometry in structural glycobiology due in large part to the gas-phase separation attributes not typically observed by orthogonal methods.
29790113	2	61	theme	Lewisx	564:569	arg1	epitopes					582:589	the Lewisx and Lewisy epitopes	560:589	the Lewisx and Lewisy epitopes	560:589	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	2	62	theme	negative	418:425	arg1	dissociation					449:460	negative ion collision-induced dissociation	418:460	negative ion collision-induced dissociation	418:460	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	0	63	dep	Studies	11:17	arg1	Spectrometry					65:76	Ion Mobility Mass Spectrometry	47:76	Ion Mobility Mass Spectrometry	47:76	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	63	dep	Studies	11:17	arg1	Fragmentation					100:112	Collision-Induced Fragmentation	82:112	Collision-Induced Fragmentation of Negative Ions	82:129	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	63	dep	Studies	11:17	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	6	64	theme	valuable	1200:1207	arg1	information					1220:1230	additional valuable structural information	1189:1230	additional valuable structural information that was missing from the CID spectra alone	1189:1274	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	2	65	theme	wave	386:389	arg1	mobility					395:402	traveling wave ion mobility	376:402	traveling wave ion mobility combined with negative ion collision-induced dissociation	376:460	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29790113	6	66	theme	ion	1115:1117	arg1	mobility					1119:1126	ion mobility	1115:1126	ion mobility	1115:1126	Some isobaric fragment ions produced prior to ion mobility could subsequently be separated and, in some cases, provided additional valuable structural information that was missing from the CID spectra alone.
29790113	0	67	theme	Mass	60:63	arg1	Spectrometry					65:76	Ion Mobility Mass Spectrometry	47:76	Ion Mobility Mass Spectrometry	47:76	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	0	67	theme	Mass	60:63	arg1	Studies					11:17	Structural Studies	0:17	Structural Studies of Fucosylated N-Glycans	0:42	Structural Studies of Fucosylated N-Glycans by Ion Mobility Mass Spectrometry and Collision-Induced Fragmentation of Negative Ions.
29790113	2	68	theme	traveling	376:384	arg1	mobility					395:402	traveling wave ion mobility	376:402	traveling wave ion mobility combined with negative ion collision-induced dissociation	376:460	Here, we evaluate the capability of traveling wave ion mobility combined with negative ion collision-induced dissociation to provide structural information on N-linked glycans containing multiple fucose residues forming the Lewisx and Lewisy epitopes.
29530659	2	0	theme	antigenic	289:297	arg1	characterization					311:326	antigenic and genetic characterization	289:326	antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively	289:456	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	9	1	from	source	1445:1450	arg1	ducks					1471:1475	ducks	1471:1475	ducks in India	1471:1484	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	7	2	theme	HA	1032:1033	arg1	gene					1035:1038	the HA gene	1028:1038	the HA gene	1028:1038	Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II).
29530659	6	3	link	N-linked	930:937	arg1	glycosylation					939:951	an additional N-linked glycosylation	916:951	an additional N-linked glycosylation	916:951	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	9	4	theme	H6N2	1355:1358	arg1	viruses					1360:1366	the two H6N2 viruses	1347:1366	the two H6N2 viruses	1347:1366	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	10	5	from	surveillance	1512:1523	arg1	poultry					1528:1534	poultry	1528:1534	poultry	1528:1534	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	10	5	from	surveillance	1512:1523	arg1	birds					1545:1549	wild birds	1540:1549	wild birds	1540:1549	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	8	6	theme	neuraminidase	1138:1150	arg1	Phylogeny					1125:1133	Phylogeny	1125:1133	Phylogeny of neuraminidase and internal gene segments	1125:1177	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	3	7	from	positions	604:612	arg1	differences					586:596	amino acid differences	575:596	amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1	575:656	Hemagglutination inhibition assay revealed antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1.
29530659	8	8	theme	internal	1156:1163	arg1	segments					1170:1177	internal gene segments	1156:1177	internal gene segments	1156:1177	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	10	9	theme	continued	1498:1506	arg1	surveillance					1512:1523	continued AIV surveillance	1498:1523	continued AIV surveillance in poultry and wild birds	1498:1549	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	7	10	theme	Phylogenetic	1003:1014	arg1	analysis					1016:1023	Phylogenetic analysis	1003:1023	Phylogenetic analysis of the HA gene	1003:1038	Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II).
29530659	8	11	theme	segments	1170:1177	arg1	Phylogeny					1125:1133	Phylogeny	1125:1133	Phylogeny of neuraminidase and internal gene segments	1125:1177	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	8	12	theme	gene	1277:1280	arg1	constellations					1282:1295	different gene constellations	1267:1295	different gene constellations	1267:1295	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	9	13	theme	wild	1393:1396	arg1	birds					1398:1402	migratory wild birds	1383:1402	migratory wild birds	1383:1402	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	9	14	theme	Central	1411:1417	arg1	flyway					1425:1430	the Central Asian flyway	1407:1430	the Central Asian flyway	1407:1430	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	0	15	theme	reassortant	19:29	arg1	viruses					52:58	novel reassortant H6N2 avian influenza viruses	13:58	novel reassortant H6N2 avian influenza viruses	13:58	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	9	16	dep	suggest	1310:1316	arg1	source					1445:1450	the source	1441:1450	the source of H6N2 viruses	1441:1466	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	1	17	from	poultry	201:207	arg1	prevalent					176:184	prevalent	176:184	prevalent	176:184	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	17	from	poultry	201:207	arg1	reports					90:96	The recent reports	79:96	The recent reports	79:96	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	5	18	theme	V27I	840:843	arg1	marker					854:859	V27I mutation marker	840:859	V27I mutation marker for amantadine resistance in M2	840:891	However, Kerala14 had V27I mutation marker for amantadine resistance in M2.
29530659	5	19	contain	had	836:838	arg2	marker					854:859	V27I mutation marker	840:859	V27I mutation marker for amantadine resistance in M2	840:891	However, Kerala14 had V27I mutation marker for amantadine resistance in M2.
29530659	5	19	contain	had	836:838	arg1	Kerala14					827:834	Kerala14	827:834	Kerala14	827:834	However, Kerala14 had V27I mutation marker for amantadine resistance in M2.
29530659	3	20	theme	acid	581:584	arg1	differences					586:596	amino acid differences	575:596	amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1	575:656	Hemagglutination inhibition assay revealed antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1.
29530659	9	21	from	ducks	1471:1475	arg1	India					1480:1484	India	1480:1484	India	1480:1484	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	1	22	theme	infection	107:115	arg1	prevalent					176:184	prevalent	176:184	prevalent	176:184	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	22	theme	infection	107:115	arg1	reports					90:96	The recent reports	79:96	The recent reports	79:96	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	8	23	with	distinct	1253:1260	arg1	constellations					1282:1295	different gene constellations	1267:1295	different gene constellations	1267:1295	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	1	24	theme	H6	124:125	arg1	AIV					160:162	AIV	160:162	AIV	160:162	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	24	theme	H6	124:125	arg1	viruses					151:157	H6 subtype avian influenza viruses	124:157	H6 subtype avian influenza viruses (AIV)	124:163	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	6	25	theme	N-linked	930:937	arg1	glycosylation					939:951	an additional N-linked glycosylation	916:951	an additional N-linked glycosylation	916:951	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	7	26	dep	belonged	1071:1078	arg1	Asia					1115:1118	Asia II	1115:1121	Asia II	1115:1121	Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II).
29530659	7	26	dep	belonged	1071:1078	arg1	Eurasian					1102:1109	Eurasian	1102:1109	Eurasian	1102:1109	Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II).
29530659	1	27	theme	avian	135:139	arg1	AIV					160:162	AIV	160:162	AIV	160:162	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	27	theme	avian	135:139	arg1	viruses					151:157	H6 subtype avian influenza viruses	124:157	H6 subtype avian influenza viruses (AIV)	124:163	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	4	28	with	pathogenic	766:775	arg1	specificity					749:759	avian receptor specificity	734:759	avian receptor specificity	734:759	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	0	29	from	Emergence	0:8	arg1	ducks					63:67	ducks	63:67	ducks in India	63:76	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	3	30	theme	antigenic	502:510	arg1	divergence					512:521	antigenic divergence	502:521	antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1	502:656	Hemagglutination inhibition assay revealed antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1.
29530659	9	31	theme	H6N2	1455:1458	arg1	viruses					1460:1466	H6N2 viruses	1455:1466	H6N2 viruses	1455:1466	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	8	32	theme	different	1267:1275	arg1	constellations					1282:1295	different gene constellations	1267:1295	different gene constellations	1267:1295	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	2	33	theme	viruses	340:346	arg1	characterization					311:326	antigenic and genetic characterization	289:326	antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively	289:456	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	6	34	theme	Kerala14	987:994	arg1	virus					996:1000	Kerala14 virus	987:1000	Kerala14 virus	987:1000	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	4	35	theme	sequence	662:669	arg1	analyses					671:678	The sequence analyses	658:678	The sequence analyses	658:678	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	5	36	theme	amantadine	865:874	arg1	resistance					876:885	amantadine resistance	865:885	amantadine resistance in M2	865:891	However, Kerala14 had V27I mutation marker for amantadine resistance in M2.
29530659	2	37	theme	healthy	373:379	arg1	ducks					390:394	apparently healthy domestic ducks	362:394	apparently healthy domestic ducks in Kerala and Assam, India	362:421	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	0	38	theme	novel	13:17	arg1	viruses					52:58	novel reassortant H6N2 avian influenza viruses	13:58	novel reassortant H6N2 avian influenza viruses	13:58	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	4	39	theme	receptor	740:747	arg1	specificity					749:759	avian receptor specificity	734:759	avian receptor specificity	734:759	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	10	40	theme	early	1568:1572	arg1	detection					1574:1582	early detection	1568:1582	early detection of emergence of novel strains with pandemic potential	1568:1636	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	9	41	theme	viruses	1360:1366	arg1	introductions					1330:1342	independent introductions	1318:1342	independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway	1318:1430	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	1	42	theme	possible	247:254	arg1	strain					265:270	a possible pandemic strain	245:270	a possible pandemic strain	245:270	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	0	43	theme	H6N2	31:34	arg1	viruses					52:58	novel reassortant H6N2 avian influenza viruses	13:58	novel reassortant H6N2 avian influenza viruses	13:58	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	2	44	attach	isolated	348:355	arg2	viruses					340:346	two H6N2 viruses	331:346	two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively	331:456	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	2	44	attach	isolated	348:355	arg1	ducks					390:394	apparently healthy domestic ducks	362:394	apparently healthy domestic ducks in Kerala and Assam, India	362:421	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	9	45	from	birds	1398:1402	arg1	flyway					1425:1430	the Central Asian flyway	1407:1430	the Central Asian flyway	1407:1430	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	10	46	theme	strains	1606:1612	arg1	emergence					1587:1595	emergence	1587:1595	emergence of novel strains with pandemic potential	1587:1636	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	0	47	theme	influenza	42:50	arg1	viruses					52:58	novel reassortant H6N2 avian influenza viruses	13:58	novel reassortant H6N2 avian influenza viruses	13:58	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	2	48	from	ducks	390:394	arg1	Kerala					399:404	Kerala	399:404	Kerala	399:404	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	2	48	from	ducks	390:394	arg1	India					417:421	India	417:421	India	417:421	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	10	49	with	strains	1606:1612	arg1	potential					1628:1636	pandemic potential	1619:1636	pandemic potential	1619:1636	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	4	50	theme	avian	716:720	arg1	origin					722:727	avian origin	716:727	avian origin	716:727	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	4	50	theme	avian	716:720	arg1	pathogenic					766:775	pathogenic	766:775	pathogenic	766:775	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	4	50	theme	avian	716:720	arg1	viruses					704:710	the viruses	700:710	both the viruses	695:710	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	9	51	from	India	1373:1377	arg1	flyway					1425:1430	the Central Asian flyway	1407:1430	the Central Asian flyway	1407:1430	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	9	52	theme	independent	1318:1328	arg1	introductions					1330:1342	independent introductions	1318:1342	independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway	1318:1430	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	7	53	theme	gene	1035:1038	arg1	analysis					1016:1023	Phylogenetic analysis	1003:1023	Phylogenetic analysis of the HA gene	1003:1038	Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II).
29530659	6	54	gly	glycosylation	939:951	arg1	HA2					956:958	HA2	956:958	HA2	956:958	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	10	55	theme	pandemic	1619:1626	arg1	potential					1628:1636	pandemic potential	1619:1636	pandemic potential	1619:1636	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	10	56	theme	spread	1659:1664	arg1	control					1642:1648	control	1642:1648	control of their spread	1642:1664	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	10	56	theme	spread	1659:1664	arg1	detection					1574:1582	early detection	1568:1582	early detection of emergence of novel strains with pandemic potential	1568:1636	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	3	57	theme	inhibition	476:485	arg1	assay					487:491	Hemagglutination inhibition assay	459:491	Hemagglutination inhibition assay	459:491	Hemagglutination inhibition assay revealed antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1.
29530659	1	58	theme	influenza	141:149	arg1	AIV					160:162	AIV	160:162	AIV	160:162	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	58	theme	influenza	141:149	arg1	viruses					151:157	H6 subtype avian influenza viruses	124:157	H6 subtype avian influenza viruses (AIV)	124:163	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	10	59	theme	AIV	1508:1510	arg1	surveillance					1512:1523	continued AIV surveillance	1498:1523	continued AIV surveillance in poultry and wild birds	1498:1549	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	6	60	theme	Assam15	898:904	arg1	virus					906:910	The Assam15 virus	894:910	The Assam15 virus	894:910	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	9	61	theme	migratory	1383:1391	arg1	birds					1398:1402	migratory wild birds	1383:1402	migratory wild birds	1383:1402	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	8	62	theme	gene	1165:1168	arg1	segments					1170:1177	internal gene segments	1156:1177	internal gene segments	1156:1177	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	0	63	from	ducks	63:67	arg1	India					72:76	India	72:76	India	72:76	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	1	64	from	prevalent	176:184	arg1	poultry					201:207	terrestrial poultry	189:207	terrestrial poultry	189:207	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	3	65	theme	amino	575:579	arg1	differences					586:596	amino acid differences	575:596	amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1	575:656	Hemagglutination inhibition assay revealed antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1.
29530659	9	66	theme	Asian	1419:1423	arg1	flyway					1425:1430	the Central Asian flyway	1407:1430	the Central Asian flyway	1407:1430	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	4	67	dep	viruses	704:710	arg1	both					695:698	both	695:698	both	695:698	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	1	68	theme	human	101:105	arg1	infection					107:115	human infection	101:115	human infection due to H6 subtype avian influenza viruses (AIV)	101:163	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	6	69	dep	had	912:914	arg1	position					961:968	position 557	961:972	position 557	961:972	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	8	70	theme	novel	1214:1218	arg1	viruses					1202:1208	both the viruses	1193:1208	both the viruses	1193:1208	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	8	70	theme	novel	1214:1218	arg1	reassortants					1220:1231	novel reassortants	1214:1231	novel reassortants	1214:1231	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	8	70	theme	novel	1214:1218	arg1	distinct					1253:1260	distinct	1253:1260	distinct	1253:1260	Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations.
29530659	1	71	theme	subtype	127:133	arg1	AIV					160:162	AIV	160:162	AIV	160:162	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	71	theme	subtype	127:133	arg1	viruses					151:157	H6 subtype avian influenza viruses	124:157	H6 subtype avian influenza viruses (AIV)	124:163	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	6	72	theme	additional	919:928	arg1	glycosylation					939:951	an additional N-linked glycosylation	916:951	an additional N-linked glycosylation	916:951	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	9	73	theme	viruses	1460:1466	arg1	source					1445:1450	the source	1441:1450	the source of H6N2 viruses	1441:1466	The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
29530659	5	74	theme	mutation	845:852	arg1	marker					854:859	V27I mutation marker	840:859	V27I mutation marker for amantadine resistance in M2	840:891	However, Kerala14 had V27I mutation marker for amantadine resistance in M2.
29530659	2	75	theme	H6N2	335:338	arg1	viruses					340:346	two H6N2 viruses	331:346	two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively	331:456	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	7	76	theme	distinct	1083:1090	arg1	lineages					1092:1099	distinct lineages	1083:1099	distinct lineages	1083:1099	Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II).
29530659	1	77	theme	terrestrial	189:199	arg1	poultry					201:207	terrestrial poultry	189:207	terrestrial poultry	189:207	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	7	78	dep	viruses	1063:1069	arg1	both					1054:1057	both	1054:1057	both	1054:1057	Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II).
29530659	6	79	contain	had	912:914	arg1	virus					906:910	The Assam15 virus	894:910	The Assam15 virus	894:910	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	6	79	contain	had	912:914	arg2	glycosylation					939:951	an additional N-linked glycosylation	916:951	an additional N-linked glycosylation	916:951	The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus.
29530659	10	80	theme	wild	1540:1543	arg1	birds					1545:1549	wild birds	1540:1549	wild birds	1540:1549	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	4	81	dep	pathogenic	766:775	arg1	origin					722:727	avian origin	716:727	avian origin	716:727	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	4	81	dep	pathogenic	766:775	arg1	pathogenic					766:775	pathogenic	766:775	pathogenic	766:775	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	4	81	dep	pathogenic	766:775	arg1	viruses					704:710	the viruses	700:710	both the viruses	695:710	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	1	82	theme	virus	236:240	arg1	evolution					219:227	evolution	219:227	evolution of the virus to a possible pandemic strain	219:270	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	83	theme	recent	83:88	arg1	prevalent					176:184	prevalent	176:184	prevalent	176:184	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	1	83	theme	recent	83:88	arg1	reports					90:96	The recent reports	79:96	The recent reports	79:96	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	2	84	theme	domestic	381:388	arg1	ducks					390:394	apparently healthy domestic ducks	362:394	apparently healthy domestic ducks in Kerala and Assam, India	362:421	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	0	85	theme	avian	36:40	arg1	viruses					52:58	novel reassortant H6N2 avian influenza viruses	13:58	novel reassortant H6N2 avian influenza viruses	13:58	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	4	86	theme	avian	734:738	arg1	specificity					749:759	avian receptor specificity	734:759	avian receptor specificity	734:759	The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir.
29530659	0	87	theme	viruses	52:58	arg1	Emergence					0:8	Emergence	0:8	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India	0:76	Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India.
29530659	1	88	theme	pandemic	256:263	arg1	strain					265:270	a possible pandemic strain	245:270	a possible pandemic strain	245:270	The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain.
29530659	2	89	theme	genetic	303:309	arg1	characterization					311:326	antigenic and genetic characterization	289:326	antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively	289:456	Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively.
29530659	10	90	theme	novel	1600:1604	arg1	strains					1606:1612	novel strains	1600:1612	novel strains with pandemic potential	1600:1636	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	5	91	from	resistance	876:885	arg1	M2					890:891	M2	890:891	M2	890:891	However, Kerala14 had V27I mutation marker for amantadine resistance in M2.
29530659	10	92	theme	emergence	1587:1595	arg1	control					1642:1648	control	1642:1648	control of their spread	1642:1664	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	10	92	theme	emergence	1587:1595	arg1	detection					1574:1582	early detection	1568:1582	early detection of emergence of novel strains with pandemic potential	1568:1636	Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.
29530659	3	93	theme	Hemagglutination	459:474	arg1	assay					487:491	Hemagglutination inhibition assay	459:491	Hemagglutination inhibition assay	459:491	Hemagglutination inhibition assay revealed antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1.
31430298	0	0	theme	ionomer	72:78	arg1	properties					87:96	glass ionomer cement properties	66:96	glass ionomer cement properties	66:96	Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
31430298	6	1	theme	diametral	740:748	arg1	strength					758:765	4) diametral tensile strength	737:765	4) diametral tensile strength	737:765	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	4	2	theme	confocal	524:531	arg1	microscopy-CLSM					548:562	confocal laser scanning microscopy-CLSM	524:562	confocal laser scanning microscopy-CLSM	524:562	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	2	theme	confocal	524:531	arg1	assays					429:434	Biological assays	418:434	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	0	3	theme	glass	66:70	arg1	properties					87:96	glass ionomer cement properties	66:96	glass ionomer cement properties	66:96	Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
31430298	4	4	theme	cariogenic	468:477	arg1	bacteria					479:486	some cariogenic bacteria	463:486	some cariogenic bacteria	463:486	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	14	5	theme	GIC	1661:1663	arg1	hardness					1620:1627	the hardness	1616:1627	the hardness	1616:1627	Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
31430298	14	5	theme	GIC	1661:1663	arg1	biocompatibility					1637:1652	the biocompatibility	1633:1652	the biocompatibility of the GIC	1633:1663	Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
31430298	6	6	dep	assays	674:679	arg1	roughness					685:693	roughness	685:693	roughness	685:693	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	6	dep	assays	674:679	arg1	3					709:709	3	709:709	3	709:709	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	6	dep	assays	674:679	arg1	properties					663:672	Physical properties	654:672	Physical properties	654:672	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	6	dep	assays	674:679	arg1	strength					758:765	4) diametral tensile strength	737:765	4) diametral tensile strength	737:765	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	6	dep	assays	674:679	arg1	2					696:696	2	696:696	2	696:696	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	6	dep	assays	674:679	arg1	strength					724:731	compressive strength	712:731	compressive strength	712:731	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	6	dep	assays	674:679	arg1	hardness					699:706	hardness	699:706	hardness	699:706	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	6	dep	assays	674:679	arg1	1					682:682	1	682:682	1	682:682	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	4	7	theme	scanning	539:546	arg1	microscopy-CLSM					548:562	confocal laser scanning microscopy-CLSM	524:562	confocal laser scanning microscopy-CLSM	524:562	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	7	theme	scanning	539:546	arg1	assays					429:434	Biological assays	418:434	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	0	8	theme	cement	80:85	arg1	properties					87:96	glass ionomer cement properties	66:96	glass ionomer cement properties	66:96	Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
31430298	4	9	dep	formation	510:518	arg1	2					489:489	2	489:489	2	489:489	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	9	10	theme	Polysaccharides	971:985	arg1	levels					987:992	Polysaccharides levels	971:992	Polysaccharides levels	971:992	Polysaccharides levels increased over time, similarly over groups (p>0.05).
31430298	11	11	theme	tensile	1272:1278	arg1	strength					1280:1287	compressive and diametral tensile strength	1246:1287	compressive and diametral tensile strength	1246:1287	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	4	12	theme	laser	533:537	arg1	microscopy-CLSM					548:562	confocal laser scanning microscopy-CLSM	524:562	confocal laser scanning microscopy-CLSM	524:562	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	12	theme	laser	533:537	arg1	assays					429:434	Biological assays	418:434	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	2	13	from	effect	200:205	arg1	properties					244:253	biological, physical and chemical properties	210:253	biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM)	210:335	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	8	14	theme	short-term	897:906	arg1	reduction					908:916	a short-term reduction	895:916	a short-term reduction in bacterial viability but similar biomass (p>0.05)	895:968	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	8	15	theme	larger	844:849	arg1	zones					851:855	larger zones	844:855	larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05)	844:968	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	8	16	with	biofilms	881:888	arg1	reduction					908:916	a short-term reduction	895:916	a short-term reduction in bacterial viability but similar biomass (p>0.05)	895:968	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	1	17	theme	novel	156:160	arg1	material					174:181	a novel restorative material	154:181	a novel restorative material	154:181	A series of experiments were conducted to characterize a novel restorative material.
31430298	4	18	theme	agar	440:443	arg1	diffusion					445:453	agar diffusion	440:453	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	3	19	dep	assays	375:380	arg1	assays					375:380	all assays	371:380	all assays: GIC+tt-farnesol and GIC (control)	371:415	Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control).
31430298	3	19	dep	assays	375:380	arg1	control					408:414	control	408:414	control	408:414	Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control).
31430298	3	19	dep	assays	375:380	arg1	GIC					403:405	GIC	403:405	GIC	403:405	Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control).
31430298	3	19	dep	assays	375:380	arg1	GIC+tt-farnesol					383:397	GIC+tt-farnesol	383:397	GIC+tt-farnesol	383:397	Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control).
31430298	8	20	theme	inhibition	860:869	arg1	zones					851:855	larger zones	844:855	larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05)	844:968	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	1	21	theme	restorative	162:172	arg1	material					174:181	a novel restorative material	154:181	a novel restorative material	154:181	A series of experiments were conducted to characterize a novel restorative material.
31430298	4	22	dep	S.	492:493	arg1	mutans					495:500	mutans	495:500	mutans	495:500	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	11	23	theme	cell	1213:1216	arg1	viability					1218:1226	the HaCaT cell viability	1203:1226	the HaCaT cell viability	1203:1226	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	11	24	theme	diametral	1262:1270	arg1	strength					1280:1287	compressive and diametral tensile strength	1246:1287	compressive and diametral tensile strength	1246:1287	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	13	25	theme	little	1500:1505	arg1	effect					1507:1512	a little effect	1498:1512	a little effect	1498:1512	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	2	26	theme	adding-the	285:294	arg1	tt-farnesol					316:326	glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol	258:326	glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM)	258:335	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	2	26	theme	adding-the	285:294	arg1	mM					333:334	900 mM	329:334	900 mM	329:334	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	13	27	contain	had	1494:1496	arg2	effect					1507:1512	a little effect	1498:1512	a little effect	1498:1512	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	13	27	contain	had	1494:1496	arg1	incorporation					1408:1420	The incorporation	1404:1420	The incorporation of tt-farnesol into GIC	1404:1444	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	4	28	theme	S.	492:493	arg1	assays					429:434	Biological assays	418:434	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	28	theme	S.	492:493	arg1	formation					510:518	S. mutans biofilm formation	492:518	S. mutans biofilm formation	492:518	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	11	29	dep	affected	1340:1347	arg1	p<0.05					1350:1355	p<0.05	1350:1355	p<0.05	1350:1355	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	13	30	theme	tt-farnesol	1425:1435	arg1	incorporation					1408:1420	The incorporation	1404:1420	The incorporation of tt-farnesol into GIC	1404:1444	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	14	31	theme	material	1738:1745	arg1	properties					1708:1717	negatively other physical properties	1682:1717	negatively other physical properties of the restorative material	1682:1745	Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
31430298	8	32	theme	bacterial	921:929	arg1	viability					931:939	bacterial viability	921:939	bacterial viability	921:939	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	13	33	theme	bacteria	1481:1488	arg1	growth					1460:1465	the growth	1456:1465	the growth of cariogenic bacteria	1456:1488	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	0	34	theme	antimicrobial	25:37	arg1	trans-farnesol					6:19	trans-farnesol	6:19	trans-farnesol	6:19	Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
31430298	0	34	theme	antimicrobial	25:37	arg1	compound					47:54	an antimicrobial natural compound	22:54	an antimicrobial natural compound	22:54	Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
31430298	4	35	theme	biofilm	502:508	arg1	assays					429:434	Biological assays	418:434	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	35	theme	biofilm	502:508	arg1	formation					510:518	S. mutans biofilm formation	492:518	S. mutans biofilm formation	492:518	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	8	36	theme	similar	945:951	arg1	p>0.05					962:967	p>0.05	962:967	p>0.05	962:967	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	8	36	theme	similar	945:951	arg1	biomass					953:959	similar biomass	945:959	similar biomass (p>0.05)	945:968	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	11	37	from	impact	1236:1241	arg1	roughness					1293:1301	roughness	1293:1301	roughness	1293:1301	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	11	37	from	impact	1236:1241	arg1	strength					1280:1287	compressive and diametral tensile strength	1246:1287	compressive and diametral tensile strength	1246:1287	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	2	38	theme	physical	222:229	arg1	properties					244:253	biological, physical and chemical properties	210:253	biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM)	210:335	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	11	39	theme	HaCaT	1207:1211	arg1	viability					1218:1226	the HaCaT cell viability	1203:1226	the HaCaT cell viability	1203:1226	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	13	40	theme	biofilm	1566:1572	arg1	matrices					1574:1581	the biofilm matrices	1562:1581	the biofilm matrices	1562:1581	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	5	41	dep	gtfB	568:571	arg1	MTT					622:624	4) MTT	619:624	4) MTT	619:624	3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology.
31430298	5	41	dep	gtfB	568:571	arg1	morphology					642:651	microscopic morphology	630:651	microscopic morphology	630:651	3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology.
31430298	5	41	dep	gtfB	568:571	arg1	3					565:565	3	565:565	3	565:565	3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology.
31430298	8	42	from	reduction	908:916	arg1	p>0.05					962:967	p>0.05	962:967	p>0.05	962:967	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	8	42	from	reduction	908:916	arg1	viability					931:939	bacterial viability	921:939	bacterial viability	921:939	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	8	42	from	reduction	908:916	arg1	biomass					953:959	similar biomass	945:959	similar biomass (p>0.05)	945:968	The adding of tt-farnesol to GIC led to larger zones of inhibition (p<0.05), biofilms with a short-term reduction in bacterial viability but similar biomass (p>0.05).
31430298	14	43	theme	other	1693:1697	arg1	properties					1708:1717	negatively other physical properties	1682:1717	negatively other physical properties of the restorative material	1682:1745	Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
31430298	4	44	theme	Biological	418:427	arg1	formation					510:518	S. mutans biofilm formation	492:518	S. mutans biofilm formation	492:518	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	44	theme	Biological	418:427	arg1	microscopy-CLSM					548:562	confocal laser scanning microscopy-CLSM	524:562	confocal laser scanning microscopy-CLSM	524:562	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	44	theme	Biological	418:427	arg1	assays					429:434	Biological assays	418:434	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	2	45	theme	biological	210:219	arg1	properties					244:253	biological, physical and chemical properties	210:253	biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM)	210:335	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	6	46	theme	tensile	750:756	arg1	strength					758:765	4) diametral tensile strength	737:765	4) diametral tensile strength	737:765	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	0	47	theme	natural	39:45	arg1	trans-farnesol					6:19	trans-farnesol	6:19	trans-farnesol	6:19	Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
31430298	0	47	theme	natural	39:45	arg1	compound					47:54	an antimicrobial natural compound	22:54	an antimicrobial natural compound	22:54	Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.
31430298	14	48	theme	restorative	1726:1736	arg1	material					1738:1745	the restorative material	1722:1745	the restorative material	1722:1745	Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
31430298	13	49	theme	cariogenic	1470:1479	arg1	bacteria					1481:1488	cariogenic bacteria	1470:1488	cariogenic bacteria	1470:1488	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	6	50	theme	compressive	712:722	arg1	strength					724:731	compressive strength	712:731	compressive strength	712:731	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	6	51	theme	Physical	654:661	arg1	properties					663:672	Physical properties	654:672	Physical properties	654:672	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31430298	14	52	theme	physical	1699:1706	arg1	properties					1708:1717	negatively other physical properties	1682:1717	negatively other physical properties of the restorative material	1682:1745	Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
31430298	4	53	dep	diffusion	445:453	arg1	1					437:437	1	437:437	1	437:437	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	5	54	dep	MTT	622:624	arg1	4					619:619	4	619:619	4	619:619	3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology.
31430298	14	55	dep	increased	1606:1614	arg1	influencing					1670:1680	influencing	1670:1680	not influencing negatively other physical properties of the restorative material	1666:1745	Also, the tt-farnesol increased the hardness and the biocompatibility of the GIC, not influencing negatively other physical properties of the restorative material.
31430298	1	56	theme	experiments	111:121	arg1	series					101:106	A series	99:106	A series of experiments	99:121	A series of experiments were conducted to characterize a novel restorative material.
31430298	7	57	theme	Raman	784:788	arg1	spectroscopy					790:801	Raman spectroscopy	784:801	Raman spectroscopy	784:801	Chemical assay: Raman spectroscopy.
31430298	5	58	theme	microscopic	630:640	arg1	morphology					642:651	microscopic morphology	630:651	microscopic morphology	630:651	3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology.
31430298	5	59	theme	covR	602:605	arg1	expression					607:616	covR expression	602:616	covR expression	602:616	3) gtfB, gtfC, gtfD, gbpB, vicR, and covR expression; 4) MTT and microscopic morphology.
31430298	11	60	theme	compressive	1246:1256	arg1	strength					1280:1287	compressive and diametral tensile strength	1246:1287	compressive and diametral tensile strength	1246:1287	The tt-farnesol increased the HaCaT cell viability without impact on compressive and diametral tensile strength and roughness although the hardness was positively affected (p<0.05).
31430298	2	61	theme	occurring	306:314	arg1	tt-farnesol					316:326	glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol	258:326	glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM)	258:335	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	2	61	theme	occurring	306:314	arg1	mM					333:334	900 mM	329:334	900 mM	329:334	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	7	62	theme	Chemical	768:775	arg1	assay					777:781	Chemical assay	768:781	Chemical assay	768:781	Chemical assay: Raman spectroscopy.
31430298	2	63	theme	tt-farnesol	316:326	arg1	properties					244:253	biological, physical and chemical properties	210:253	biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM)	210:335	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	4	64	dep	assays	429:434	arg1	assays					429:434	Biological assays	418:434	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	64	dep	assays	429:434	arg1	microscopy-CLSM					548:562	confocal laser scanning microscopy-CLSM	524:562	confocal laser scanning microscopy-CLSM	524:562	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	64	dep	assays	429:434	arg1	diffusion					445:453	agar diffusion	440:453	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.	418:563	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	4	64	dep	assays	429:434	arg1	formation					510:518	S. mutans biofilm formation	492:518	S. mutans biofilm formation	492:518	Biological assays: 1) agar diffusion against some cariogenic bacteria; 2) S. mutans biofilm formation and confocal laser scanning microscopy-CLSM.
31430298	2	65	theme	chemical	235:242	arg1	properties					244:253	biological, physical and chemical properties	210:253	biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM)	210:335	We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM).
31430298	13	66	theme	matrices	1574:1581	arg1	composition					1521:1531	composition	1521:1531	composition	1521:1531	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	13	66	theme	matrices	1574:1581	arg1	physiology					1548:1557	physiology	1548:1557	physiology	1548:1557	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	13	66	theme	matrices	1574:1581	arg1	structure					1534:1542	structure	1534:1542	structure	1534:1542	The incorporation of tt-farnesol into GIC inhibited the growth of cariogenic bacteria but had a little effect on the composition, structure and physiology of the biofilm matrices.
31430298	12	67	theme	tt-farnesol	1391:1401	arg1	presence					1379:1386	the presence	1375:1386	the presence of tt-farnesol	1375:1401	Raman confirmed the presence of tt-farnesol.
31430298	7	68	dep	spectroscopy	790:801	arg1	assay					777:781	Chemical assay	768:781	Chemical assay	768:781	Chemical assay: Raman spectroscopy.
31430298	6	69	dep	strength	758:765	arg1	4					737:737	4	737:737	4	737:737	Physical properties assays: 1) roughness; 2) hardness; 3) compressive strength and 4) diametral tensile strength.
31722217	0	0	theme	Notch	75:79	arg1	Signaling					81:89	Notch Signaling	75:89	Notch Signaling in Drosophila	75:103	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila.
31722217	7	1	theme	context-dependent	1086:1102	arg1	roles					1104:1108	the combinatorial and context-dependent roles	1064:1108	the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions	1064:1190	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	2	2	from	development	436:446	arg1	presence					463:470	presence	463:470	presence	463:470	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	2	2	from	development	436:446	arg1	absence					475:481	absence	475:481	absence	475:481	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	7	3	from	glycans	1129:1135	arg1	sites					1146:1150	these sites	1140:1150	these sites	1140:1150	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	4	4	from	inhibition	756:765	arg1	embryos					770:776	embryos	770:776	embryos	770:776	O-Fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos.
31722217	1	5	theme	Notch	173:177	arg1	receptors					179:187	Notch receptors	173:187	Notch receptors	173:187	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	1	6	theme	Notch	271:275	arg1	repeats					312:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	7	7	theme	combinatorial	1068:1080	arg1	roles					1104:1108	the combinatorial and context-dependent roles	1064:1108	the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions	1064:1190	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	5	8	from	EGF9	904:907	arg1	contribution					886:897	a minor contribution	878:897	a minor contribution from EGF9	878:907	However, wing vein development depends on the addition of GlcNAc to EGF8 and EGF12 by Fringe, with a minor contribution from EGF9.
31722217	4	9	theme	Delta-mediated	733:746	arg1	inhibition					756:765	Delta-mediated lateral inhibition	733:765	Delta-mediated lateral inhibition in embryos	733:776	O-Fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos.
31722217	4	10	from	monosaccharide	665:678	arg1	EGF12					683:687	EGF12	683:687	EGF12	683:687	O-Fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos.
31722217	4	10	from	monosaccharide	665:678	arg1	absence					697:703	the absence	693:703	the absence of Fringe	693:713	O-Fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos.
31722217	1	11	theme	epidermal	277:285	arg1	repeats					312:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	3	12	theme	important	543:551	arg1	roles					553:557	important roles	543:557	important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans	543:615	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	1	13	theme	growth	287:292	arg1	repeats					312:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	7	14	theme	Notch-ligand	1166:1177	arg1	interactions					1179:1190	Drosophila Notch-ligand interactions	1155:1190	Drosophila Notch-ligand interactions	1155:1190	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	7	15	from	sites	1146:1150	arg1	roles					1104:1108	the combinatorial and context-dependent roles	1064:1108	the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions	1064:1190	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	4	16	theme	O-Fucose	656:663	arg1	monosaccharide					665:678	O-Fucose monosaccharide	656:678	O-Fucose monosaccharide on EGF12 (in the absence of Fringe)	656:714	O-Fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos.
31722217	1	17	theme	receptors	179:187	arg1	binding					162:168	the binding	158:168	the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands	158:230	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	7	18	theme	glycans	1129:1135	arg1	roles					1104:1108	the combinatorial and context-dependent roles	1064:1108	the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions	1064:1190	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	1	19	link	O-linked	252:259	arg1	fucose					261:266	O-linked fucose	252:266	O-linked fucose on Notch epidermal growth factor-like (EGF) repeats	252:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	4	20	theme	lateral	748:754	arg1	inhibition					756:765	Delta-mediated lateral inhibition	733:765	Delta-mediated lateral inhibition in embryos	733:776	O-Fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos.
31722217	2	21	theme	Notch	407:411	arg1	activity					413:420	Notch activity	407:420	Notch activity	407:420	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	6	22	theme	EGF8	934:937	arg1	modifications					917:929	Fringe modifications	910:929	Fringe modifications of EGF8 and EGF12	910:947	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	3	23	theme	Drosophila	562:571	arg1	signaling					579:587	Drosophila Notch signaling	562:587	Drosophila Notch signaling	562:587	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	1	24	theme	Delta/DLL	192:200	arg1	ligands					224:230	Delta/DLL versus Serrate/Jagged ligands	192:230	Delta/DLL versus Serrate/Jagged ligands	192:230	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	5	25	theme	wing	788:791	arg1	development					798:808	wing vein development	788:808	wing vein development	788:808	However, wing vein development depends on the addition of GlcNAc to EGF8 and EGF12 by Fringe, with a minor contribution from EGF9.
31722217	1	26	theme	factor-like	294:304	arg1	repeats					312:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	2	27	dep	presence	463:470	arg1	the					459:461	the	459:461	the	459:461	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	3	28	theme	Notch	573:577	arg1	signaling					579:587	Drosophila Notch signaling	562:587	Drosophila Notch signaling	562:587	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	6	29	theme	wing	1026:1029	arg1	formation					1038:1046	normal wing margin formation	1019:1046	normal wing margin formation	1019:1046	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	0	30	theme	Notch	26:30	arg1	Repeats					36:42	Specific Notch EGF Repeats	17:42	Specific Notch EGF Repeats	17:42	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila.
31722217	4	31	theme	Fringe	708:713	arg1	absence					697:703	the absence	693:703	the absence of Fringe	693:713	O-Fucose monosaccharide on EGF12 (in the absence of Fringe) is essential for Delta-mediated lateral inhibition in embryos.
31722217	3	32	theme	GlcNAc-fucose-O	593:607	arg1	glycans					609:615	GlcNAc-fucose-O glycans	593:615	GlcNAc-fucose-O glycans	593:615	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	1	33	theme	Serrate/Jagged	209:222	arg1	ligands					224:230	Delta/DLL versus Serrate/Jagged ligands	192:230	Delta/DLL versus Serrate/Jagged ligands	192:230	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	0	34	theme	Specific	17:24	arg1	Repeats					36:42	Specific Notch EGF Repeats	17:42	Specific Notch EGF Repeats	17:42	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila.
31722217	1	35	theme	EGF	307:309	arg1	repeats					312:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	0	36	theme	Repeats	36:42	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe	0:63	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila.
31722217	6	37	theme	Fringe	910:915	arg1	modifications					917:929	Fringe modifications	910:929	Fringe modifications of EGF8 and EGF12	910:947	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	3	38	dep	sites	626:630	arg1	EGF9					639:642	EGF9	639:642	EGF9	639:642	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	3	38	dep	sites	626:630	arg1	EGF12					649:653	EGF12	649:653	EGF12	649:653	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	3	38	dep	sites	626:630	arg1	EGF8					633:636	EGF8	633:636	EGF8	633:636	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	3	38	dep	sites	626:630	arg1	sites					626:630	three sites	620:630	three sites: EGF8, EGF9, and EGF12	620:653	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	0	39	gly	Glycosylation	0:12	arg1	Repeats					36:42	Specific Notch EGF Repeats	17:42	Specific Notch EGF Repeats	17:42	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila.
31722217	2	40	theme	animal	429:434	arg1	development					436:446	animal development in vivo	429:454	animal development in vivo in the presence or absence of Fringe	429:491	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	0	41	theme	EGF	32:34	arg1	Repeats					36:42	Specific Notch EGF Repeats	17:42	Specific Notch EGF Repeats	17:42	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila.
31722217	2	42	theme	Fringe	486:491	arg1	presence					463:470	presence	463:470	presence	463:470	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	2	42	theme	Fringe	486:491	arg1	absence					475:481	absence	475:481	absence	475:481	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	5	43	theme	vein	793:796	arg1	development					798:808	wing vein development	788:808	wing vein development	788:808	However, wing vein development depends on the addition of GlcNAc to EGF8 and EGF12 by Fringe, with a minor contribution from EGF9.
31722217	6	44	theme	margin	1031:1036	arg1	formation					1038:1046	normal wing margin formation	1019:1046	normal wing margin formation	1019:1046	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	2	45	gly	O-fucosylation	343:356	arg2	sites					358:362	22 O-fucosylation sites	340:362	22 O-fucosylation sites	340:362	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	1	46	theme	Fringe	106:111	arg1	glycosyltransferases					113:132	Fringe glycosyltransferases	106:132	Fringe glycosyltransferases	106:132	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	7	47	theme	GlcNAc-fucose-O	1113:1127	arg1	glycans					1129:1135	GlcNAc-fucose-O glycans	1113:1135	GlcNAc-fucose-O glycans on these sites	1113:1150	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	1	48	from	fucose	261:266	arg1	repeats					312:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Notch epidermal growth factor-like (EGF) repeats	271:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	2	49	theme	O-fucosylation	343:356	arg1	sites					358:362	22 O-fucosylation sites	340:362	22 O-fucosylation sites	340:362	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	3	50	from	roles	553:557	arg1	signaling					579:587	Drosophila Notch signaling	562:587	Drosophila Notch signaling	562:587	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	7	51	from	roles	1104:1108	arg1	sites					1146:1150	these sites	1140:1150	these sites	1140:1150	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	7	51	from	roles	1104:1108	arg1	interactions					1179:1190	Drosophila Notch-ligand interactions	1155:1190	Drosophila Notch-ligand interactions	1155:1190	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31722217	6	52	theme	EGF12	943:947	arg1	modifications					917:929	Fringe modifications	910:929	Fringe modifications of EGF8 and EGF12	910:947	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	5	53	theme	minor	880:884	arg1	contribution					886:897	a minor contribution	878:897	a minor contribution from EGF9	878:907	However, wing vein development depends on the addition of GlcNAc to EGF8 and EGF12 by Fringe, with a minor contribution from EGF9.
31722217	6	54	theme	cis-inhibiting	977:990	arg1	Serrate					992:998	cis-inhibiting Serrate	977:998	cis-inhibiting Serrate	977:998	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	0	55	from	Signaling	81:89	arg1	Drosophila					94:103	Drosophila	94:103	Drosophila	94:103	Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila.
31722217	6	56	theme	normal	1019:1024	arg1	formation					1038:1046	normal wing margin formation	1019:1046	normal wing margin formation	1019:1046	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	2	57	theme	relevant	382:389	arg1	sites					391:395	the biologically relevant sites	365:395	the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe	365:491	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	5	58	theme	GlcNAc	837:842	arg1	addition					825:832	the addition	821:832	the addition of GlcNAc to EGF8 and EGF12 by Fringe	821:870	However, wing vein development depends on the addition of GlcNAc to EGF8 and EGF12 by Fringe, with a minor contribution from EGF9.
31722217	1	59	theme	O-linked	252:259	arg1	fucose					261:266	O-linked fucose	252:266	O-linked fucose on Notch epidermal growth factor-like (EGF) repeats	252:318	Fringe glycosyltransferases differentially modulate the binding of Notch receptors to Delta/DLL versus Serrate/Jagged ligands by adding GlcNAc to O-linked fucose on Notch epidermal growth factor-like (EGF) repeats.
31722217	6	60	mod	modifications	917:929	arg3	Fringe					910:915	Fringe modifications	910:929	Fringe modifications of EGF8 and EGF12	910:947	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	6	60	mod	modifications	917:929	arg1	EGF12					943:947	EGF12	943:947	EGF12	943:947	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	6	60	mod	modifications	917:929	arg1	EGF8					934:937	EGF8	934:937	EGF8	934:937	Fringe modifications of EGF8 and EGF12 together prevent Notch from cis-inhibiting Serrate, thereby promoting normal wing margin formation.
31722217	2	61	contain	has	336:338	arg2	sites					358:362	22 O-fucosylation sites	340:362	22 O-fucosylation sites	340:362	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	2	61	contain	has	336:338	arg1	Notch					330:334	Notch	330:334	Notch	330:334	Although Notch has 22 O-fucosylation sites, the biologically relevant sites affecting Notch activity during animal development in vivo in the presence or absence of Fringe are not known.
31722217	3	62	theme	assays	527:532	arg1	variety					516:522	a variety	514:522	a variety of assays	514:532	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	3	62	theme	assays	527:532	arg1	assays					527:532	assays	527:532	assays	527:532	Using a variety of assays, we find important roles in Drosophila Notch signaling for GlcNAc-fucose-O glycans on three sites: EGF8, EGF9, and EGF12.
31722217	7	63	theme	Drosophila	1155:1164	arg1	interactions					1179:1190	Drosophila Notch-ligand interactions	1155:1190	Drosophila Notch-ligand interactions	1155:1190	Our work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions.
31479573	2	0	from	glycosylation	425:437	arg1	rich					408:411	rich	408:411	rich	408:411	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	3	1	theme	inhibitory	535:544	arg1	mechanism					546:554	The inhibitory mechanism	531:554	The inhibitory mechanism	531:554	The inhibitory mechanism remains unresolved as to whether inhibition is due to steric exclusion by OLGs or a direct self-association interaction that stabilizes the domain.
31479573	6	2	theme	conformational	1180:1193	arg1	stability					1195:1203	The conformational stability	1176:1203	The conformational stability	1176:1203	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	6	3	theme	exchange	1298:1305	arg1	HXMS					1326:1329	HXMS	1326:1329	HXMS	1326:1329	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	6	3	theme	exchange	1298:1305	arg1	spectrometry					1312:1323	hydrogen-deuterium exchange mass spectrometry	1279:1323	hydrogen-deuterium exchange mass spectrometry (HXMS)	1279:1330	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	10	4	theme	proposed	1674:1681	arg1	inhibition					1683:1692	the proposed inhibition	1670:1692	the proposed inhibition	1670:1692	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	4	5	theme	A1	932:933	arg1	culture					955:961	HEK293 cell culture	943:961	HEK293 cell culture	943:961	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	5	theme	A1	932:933	arg1	domain					935:940	the wild-type glycosylated A1 domain	905:940	the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism	905:1004	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	5	6	dep	METHODS	1007:1013	arg1	METHODS					1007:1013	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	6	dep	METHODS	1007:1013	arg1	resonance					1031:1039	Surface plasmon resonance	1015:1039	Surface plasmon resonance	1015:1039	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	6	dep	METHODS	1007:1013	arg1	rheology					1056:1063	analytical rheology	1045:1063	analytical rheology	1045:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	6	7	theme	thermodynamics	1260:1273	arg1	combination					1227:1237	a combination	1225:1237	a combination of protein unfolding thermodynamics	1225:1273	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	6	7	theme	thermodynamics	1260:1273	arg1	HXMS					1326:1329	HXMS	1326:1329	HXMS	1326:1329	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	6	7	theme	thermodynamics	1260:1273	arg1	spectrometry					1312:1323	hydrogen-deuterium exchange mass spectrometry	1279:1323	hydrogen-deuterium exchange mass spectrometry (HXMS)	1279:1330	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	11	8	theme	shear	2008:2012	arg1	stress					2014:2019	rheological shear stress	1996:2019	rheological shear stress	1996:2019	Rather, they confirm a mechanism by which glycosylation sterically hinders platelet adhesion to the A1 domain at equilibrium and under rheological shear stress.
31479573	11	9	theme	platelet	1936:1943	arg1	adhesion					1945:1952	platelet adhesion	1936:1952	platelet adhesion to the A1 domain at equilibrium and under rheological shear stress	1936:2019	Rather, they confirm a mechanism by which glycosylation sterically hinders platelet adhesion to the A1 domain at equilibrium and under rheological shear stress.
31479573	6	10	theme	protein	1242:1248	arg1	thermodynamics					1260:1273	protein unfolding thermodynamics	1242:1273	protein unfolding thermodynamics	1242:1273	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	1	11	theme	molecular	142:150	arg1	basis					152:156	A molecular basis	140:156	A molecular basis for von Willebrand factor (VWF) self-inhibition	140:204	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	4	12	theme	wild-type	909:917	arg1	culture					955:961	HEK293 cell culture	943:961	HEK293 cell culture	943:961	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	12	theme	wild-type	909:917	arg1	domain					935:940	the wild-type glycosylated A1 domain	905:940	the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism	905:1004	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	13	theme	adhesive	728:735	arg1	function					737:744	The platelet adhesive function	715:744	The platelet adhesive function	715:744	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	13	theme	adhesive	728:735	arg1	OBJECTIVES					704:713	OBJECTIVES	704:713	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli)	704:885	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	9	14	theme	intrinsic	1581:1589	arg1	dynamics					1606:1613	the intrinsic conformational dynamics	1577:1613	the intrinsic conformational dynamics of the A1 domain	1577:1630	Glycosylation does not alter the intrinsic conformational dynamics of the A1 domain.
31479573	4	15	theme	self-inhibitory	980:994	arg1	mechanism					996:1004	the self-inhibitory mechanism	976:1004	the self-inhibitory mechanism	976:1004	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	1	16	theme	conformational	348:361	arg1	dynamics					363:370	the conformational dynamics	344:370	the conformational dynamics of A1	344:376	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	2	17	theme	steric	513:518	arg1	hindrance					520:528	steric hindrance	513:528	steric hindrance	513:528	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	11	18	from	equilibrium	1974:1984	arg1	adhesion					1945:1952	platelet adhesion	1936:1952	platelet adhesion to the A1 domain at equilibrium and under rheological shear stress	1936:2019	Rather, they confirm a mechanism by which glycosylation sterically hinders platelet adhesion to the A1 domain at equilibrium and under rheological shear stress.
31479573	0	19	theme	conformational	104:117	arg1	dynamics					119:126	intrinsic conformational dynamics	94:126	intrinsic conformational dynamics	94:126	Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics.
31479573	10	20	theme	flanking	1762:1769	arg1	sequences					1771:1779	these flanking sequences	1756:1779	these flanking sequences	1756:1779	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	9	21	theme	domain	1625:1630	arg1	dynamics					1606:1613	the intrinsic conformational dynamics	1577:1613	the intrinsic conformational dynamics of the A1 domain	1577:1630	Glycosylation does not alter the intrinsic conformational dynamics of the A1 domain.
31479573	11	22	theme	rheological	1996:2006	arg1	stress					2014:2019	rheological shear stress	1996:2019	rheological shear stress	1996:2019	Rather, they confirm a mechanism by which glycosylation sterically hinders platelet adhesion to the A1 domain at equilibrium and under rheological shear stress.
31479573	4	23	dep	glycosylation	854:866	arg1	coli					881:884	Escherichia coli	869:884	glycosylation (Escherichia coli)	854:885	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	1	24	theme	globular	289:296	arg1	loop					318:321	the globular A1 domain disulfide loop	285:321	the globular A1 domain disulfide loop	285:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	8	25	theme	hydrodynamic	1437:1448	arg1	size					1450:1453	the hydrodynamic size	1433:1453	the hydrodynamic size of A1	1433:1459	Glycosylation increases the hydrodynamic size of A1 and stabilizes the thermal unfolding of A1 without changing its equilibrium stability.
31479573	1	26	theme	domain	301:306	arg1	loop					318:321	the globular A1 domain disulfide loop	285:321	the globular A1 domain disulfide loop	285:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	4	27	dep	OBJECTIVES	704:713	arg1	function					737:744	The platelet adhesive function	715:744	The platelet adhesive function	715:744	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	27	dep	OBJECTIVES	704:713	arg1	stability					761:769	thermodynamic stability	747:769	thermodynamic stability	747:769	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	27	dep	OBJECTIVES	704:713	arg1	OBJECTIVES					704:713	OBJECTIVES	704:713	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli)	704:885	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	27	dep	OBJECTIVES	704:713	arg1	dynamics					791:798	conformational dynamics	776:798	conformational dynamics	776:798	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	28	theme	2M	826:827	arg1	domain					839:844	the wild-type and type 2M G1324S A1 domain	803:844	domain	839:844	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	2	29	theme	O-linked	416:423	arg1	OLG					440:442	OLG	440:442	OLG	440:442	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	2	29	theme	O-linked	416:423	arg1	glycosylation					425:437	O-linked glycosylation	416:437	O-linked glycosylation (OLG)	416:443	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	1	30	theme	loop	318:321	arg1	sequences					272:280	the N-terminal and C-terminal flanking sequences	233:280	the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop	233:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	7	31	theme	RESULTS	1333:1339	arg1	glycosylation					1344:1356	RESULTS A1 glycosylation	1333:1356	RESULTS A1 glycosylation	1333:1356	RESULTS A1 glycosylation inhibits both GPIbα binding and platelet adhesion.
31479573	4	32	theme	A1	836:837	arg1	domain					839:844	the wild-type and type 2M G1324S A1 domain	803:844	domain	839:844	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	11	33	theme	A1	1961:1962	arg1	domain					1964:1969	the A1 domain	1957:1969	the A1 domain	1957:1969	Rather, they confirm a mechanism by which glycosylation sterically hinders platelet adhesion to the A1 domain at equilibrium and under rheological shear stress.
31479573	0	34	theme	von	55:57	arg1	factor					70:75	von Willebrand factor	55:75	von Willebrand factor	55:75	Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics.
31479573	5	35	theme	analytical	1045:1054	arg1	METHODS					1007:1013	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	35	theme	analytical	1045:1054	arg1	rheology					1056:1063	analytical rheology	1045:1063	analytical rheology	1045:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	2	36	from	rich	408:411	arg1	OLG					440:442	OLG	440:442	OLG	440:442	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	2	36	from	rich	408:411	arg1	glycosylation					425:437	O-linked glycosylation	416:437	O-linked glycosylation (OLG)	416:443	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	10	37	theme	native	1800:1805	arg1	stability					1813:1821	the native state stability	1796:1821	the native state stability	1796:1821	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	1	38	theme	Willebrand	166:175	arg1	VWF					185:187	VWF	185:187	VWF	185:187	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	1	38	theme	Willebrand	166:175	arg1	factor					177:182	von Willebrand factor	162:182	von Willebrand factor (VWF) self-inhibition	162:204	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	3	39	theme	self-association	647:662	arg1	interaction					664:674	a direct self-association interaction	638:674	a direct self-association interaction that stabilizes the domain	638:701	The inhibitory mechanism remains unresolved as to whether inhibition is due to steric exclusion by OLGs or a direct self-association interaction that stabilizes the domain.
31479573	5	40	theme	Surface	1015:1021	arg1	METHODS					1007:1013	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	40	theme	Surface	1015:1021	arg1	resonance					1031:1039	Surface plasmon resonance	1015:1039	Surface plasmon resonance	1015:1039	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	1	41	theme	flanking	263:270	arg1	sequences					272:280	the N-terminal and C-terminal flanking sequences	233:280	the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop	233:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	9	42	theme	conformational	1591:1604	arg1	dynamics					1606:1613	the intrinsic conformational dynamics	1577:1613	the intrinsic conformational dynamics of the A1 domain	1577:1630	Glycosylation does not alter the intrinsic conformational dynamics of the A1 domain.
31479573	6	43	theme	mass	1307:1310	arg1	HXMS					1326:1329	HXMS	1326:1329	HXMS	1326:1329	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	6	43	theme	mass	1307:1310	arg1	spectrometry					1312:1323	hydrogen-deuterium exchange mass spectrometry	1279:1323	hydrogen-deuterium exchange mass spectrometry (HXMS)	1279:1330	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	10	44	theme	A1	1857:1858	arg1	stability					1813:1821	the native state stability	1796:1821	the native state stability	1796:1821	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	10	44	theme	A1	1857:1858	arg1	dynamics					1845:1852	the conformational dynamics	1826:1852	the conformational dynamics of A1	1826:1858	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	4	45	theme	domain	839:844	arg1	function					737:744	The platelet adhesive function	715:744	The platelet adhesive function	715:744	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	45	theme	domain	839:844	arg1	stability					761:769	thermodynamic stability	747:769	thermodynamic stability	747:769	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	45	theme	domain	839:844	arg1	OBJECTIVES					704:713	OBJECTIVES	704:713	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli)	704:885	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	6	46	theme	hydrogen-deuterium	1279:1296	arg1	HXMS					1326:1329	HXMS	1326:1329	HXMS	1326:1329	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	6	46	theme	hydrogen-deuterium	1279:1296	arg1	spectrometry					1312:1323	hydrogen-deuterium exchange mass spectrometry	1279:1323	hydrogen-deuterium exchange mass spectrometry (HXMS)	1279:1330	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	5	47	theme	platelet	1140:1147	arg1	adhesion					1149:1156	platelet adhesion	1140:1156	platelet adhesion under shear flow	1140:1173	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	48	used	utilized	1069:1076	arg2	rheology					1056:1063	analytical rheology	1045:1063	analytical rheology	1045:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	48	used	utilized	1069:1076	arg2	resonance					1031:1039	Surface plasmon resonance	1015:1039	Surface plasmon resonance	1015:1039	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	48	used	utilized	1069:1076	arg2	METHODS					1007:1013	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	10	49	dep	CONCLUSIONS	1633:1643	arg1	invalidate					1659:1668	invalidate	1659:1668	invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1	1659:1858	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	8	50	theme	A1	1458:1459	arg1	size					1450:1453	the hydrodynamic size	1433:1453	the hydrodynamic size of A1	1433:1459	Glycosylation increases the hydrodynamic size of A1 and stabilizes the thermal unfolding of A1 without changing its equilibrium stability.
31479573	4	51	theme	glycosylated	919:930	arg1	culture					955:961	HEK293 cell culture	943:961	HEK293 cell culture	943:961	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	51	theme	glycosylated	919:930	arg1	domain					935:940	the wild-type glycosylated A1 domain	905:940	the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism	905:1004	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	8	52	theme	A1	1501:1502	arg1	unfolding					1488:1496	the thermal unfolding	1476:1496	the thermal unfolding of A1	1476:1502	Glycosylation increases the hydrodynamic size of A1 and stabilizes the thermal unfolding of A1 without changing its equilibrium stability.
31479573	5	53	theme	Glycoprotein	1088:1099	arg1	GPIbα					1106:1110	GPIbα	1106:1110	GPIbα	1106:1110	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	53	theme	Glycoprotein	1088:1099	arg1	Ibα					1101:1103	Glycoprotein Ibα	1088:1103	Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow	1088:1173	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	6	54	theme	unfolding	1250:1258	arg1	thermodynamics					1260:1273	protein unfolding thermodynamics	1242:1273	protein unfolding thermodynamics	1242:1273	The conformational stability is assessed through a combination of protein unfolding thermodynamics and hydrogen-deuterium exchange mass spectrometry (HXMS).
31479573	10	55	theme	conformational	1702:1715	arg1	suppression					1717:1727	conformational suppression	1702:1727	conformational suppression	1702:1727	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	4	56	theme	cell	950:953	arg1	culture					955:961	HEK293 cell culture	943:961	HEK293 cell culture	943:961	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	56	theme	cell	950:953	arg1	domain					935:940	the wild-type glycosylated A1 domain	905:940	the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism	905:1004	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	57	gly	glycosylated	919:930	arg1	culture					955:961	HEK293 cell culture	943:961	HEK293 cell culture	943:961	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	57	gly	glycosylated	919:930	arg1	domain					935:940	the wild-type glycosylated A1 domain	905:940	the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism	905:1004	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	8	58	theme	equilibrium	1525:1535	arg1	stability					1537:1545	its equilibrium stability	1521:1545	its equilibrium stability	1521:1545	Glycosylation increases the hydrodynamic size of A1 and stabilizes the thermal unfolding of A1 without changing its equilibrium stability.
31479573	3	59	theme	steric	610:615	arg1	exclusion					617:625	steric exclusion	610:625	steric exclusion by OLGs or a direct self-association interaction that stabilizes the domain	610:701	The inhibitory mechanism remains unresolved as to whether inhibition is due to steric exclusion by OLGs or a direct self-association interaction that stabilizes the domain.
31479573	4	60	theme	platelet	719:726	arg1	function					737:744	The platelet adhesive function	715:744	The platelet adhesive function	715:744	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	60	theme	platelet	719:726	arg1	OBJECTIVES					704:713	OBJECTIVES	704:713	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli)	704:885	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	1	61	theme	von	162:164	arg1	VWF					185:187	VWF	185:187	VWF	185:187	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	1	61	theme	von	162:164	arg1	factor					177:182	von Willebrand factor	162:182	von Willebrand factor (VWF) self-inhibition	162:204	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	7	62	theme	platelet	1390:1397	arg1	adhesion					1399:1406	platelet adhesion	1390:1406	platelet adhesion	1390:1406	RESULTS A1 glycosylation inhibits both GPIbα binding and platelet adhesion.
31479573	1	63	dep	BACKGROUND	129:138	arg1	proposed					215:222	proposed	215:222	has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1	206:376	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	0	64	theme	intrinsic	94:102	arg1	dynamics					119:126	intrinsic conformational dynamics	94:126	intrinsic conformational dynamics	94:126	Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics.
31479573	1	65	theme	factor	177:182	arg1	self-inhibition					190:204	von Willebrand factor (VWF) self-inhibition	162:204	von Willebrand factor (VWF) self-inhibition	162:204	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	2	66	theme	platelet	473:480	arg1	adhesion					482:489	platelet adhesion	473:489	platelet adhesion to VWF	473:496	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	4	67	theme	HEK293	943:948	arg1	culture					955:961	HEK293 cell culture	943:961	HEK293 cell culture	943:961	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	67	theme	HEK293	943:948	arg1	domain					935:940	the wild-type glycosylated A1 domain	905:940	the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism	905:1004	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	1	68	theme	A1	375:376	arg1	dynamics					363:370	the conformational dynamics	344:370	the conformational dynamics of A1	344:376	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	9	69	theme	A1	1622:1623	arg1	domain					1625:1630	the A1 domain	1618:1630	the A1 domain	1618:1630	Glycosylation does not alter the intrinsic conformational dynamics of the A1 domain.
31479573	7	70	theme	GPIbα	1372:1376	arg1	binding					1378:1384	GPIbα binding	1372:1384	GPIbα binding	1372:1384	RESULTS A1 glycosylation inhibits both GPIbα binding and platelet adhesion.
31479573	4	71	theme	conformational	776:789	arg1	dynamics					791:798	conformational dynamics	776:798	conformational dynamics	776:798	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	2	72	theme	flanking	385:392	arg1	sequences					394:402	These flanking sequences	379:402	These flanking sequences	379:402	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	0	73	theme	platelet	34:41	arg1	adhesion					43:50	platelet adhesion	34:50	platelet adhesion to von Willebrand factor	34:75	Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics.
31479573	1	74	theme	A1	298:299	arg1	loop					318:321	the globular A1 domain disulfide loop	285:321	the globular A1 domain disulfide loop	285:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	7	75	theme	A1	1341:1342	arg1	glycosylation					1344:1356	RESULTS A1 glycosylation	1333:1356	RESULTS A1 glycosylation	1333:1356	RESULTS A1 glycosylation inhibits both GPIbα binding and platelet adhesion.
31479573	4	76	theme	thermodynamic	747:759	arg1	stability					761:769	thermodynamic stability	747:769	thermodynamic stability	747:769	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	76	theme	thermodynamic	747:759	arg1	OBJECTIVES					704:713	OBJECTIVES	704:713	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli)	704:885	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	1	77	theme	disulfide	308:316	arg1	loop					318:321	the globular A1 domain disulfide loop	285:321	the globular A1 domain disulfide loop	285:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	5	78	theme	plasmon	1023:1029	arg1	METHODS					1007:1013	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology	1007:1063	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	5	78	theme	plasmon	1023:1029	arg1	resonance					1031:1039	Surface plasmon resonance	1015:1039	Surface plasmon resonance	1015:1039	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	4	79	theme	type	821:824	arg1	domain					839:844	the wild-type and type 2M G1324S A1 domain	803:844	domain	839:844	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	0	80	theme	Willebrand	59:68	arg1	factor					70:75	von Willebrand factor	55:75	von Willebrand factor	55:75	Glycosylation sterically inhibits platelet adhesion to von Willebrand factor without altering intrinsic conformational dynamics.
31479573	5	81	theme	shear	1164:1168	arg1	flow					1170:1173	shear flow	1164:1173	shear flow	1164:1173	METHODS Surface plasmon resonance and analytical rheology are utilized to assess Glycoprotein Ibα (GPIbα) binding at equilibrium and platelet adhesion under shear flow.
31479573	2	82	link	O-linked	416:423	arg1	OLG					440:442	OLG	440:442	OLG	440:442	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	2	82	link	O-linked	416:423	arg1	glycosylation					425:437	O-linked glycosylation	416:437	O-linked glycosylation (OLG)	416:443	These flanking sequences are rich in O-linked glycosylation (OLG), which is known to suppress platelet adhesion to VWF, presumably by steric hindrance.
31479573	4	83	theme	G1324S	829:834	arg1	domain					839:844	the wild-type and type 2M G1324S A1 domain	803:844	domain	839:844	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	10	84	theme	state	1807:1811	arg1	stability					1813:1821	the native state stability	1796:1821	the native state stability	1796:1821	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	4	85	theme	wild-type	807:815	arg1	function					737:744	The platelet adhesive function	715:744	The platelet adhesive function	715:744	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	85	theme	wild-type	807:815	arg1	stability					761:769	thermodynamic stability	747:769	thermodynamic stability	747:769	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	4	85	theme	wild-type	807:815	arg1	OBJECTIVES					704:713	OBJECTIVES	704:713	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli)	704:885	OBJECTIVES The platelet adhesive function, thermodynamic stability, and conformational dynamics of the wild-type and type 2M G1324S A1 domain lacking glycosylation (Escherichia coli) are compared with the wild-type glycosylated A1 domain (HEK293 cell culture) to decipher the self-inhibitory mechanism.
31479573	3	86	theme	direct	640:645	arg1	interaction					664:674	a direct self-association interaction	638:674	a direct self-association interaction that stabilizes the domain	638:701	The inhibitory mechanism remains unresolved as to whether inhibition is due to steric exclusion by OLGs or a direct self-association interaction that stabilizes the domain.
31479573	1	87	theme	N-terminal	237:246	arg1	sequences					272:280	the N-terminal and C-terminal flanking sequences	233:280	the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop	233:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31479573	8	88	theme	thermal	1480:1486	arg1	unfolding					1488:1496	the thermal unfolding	1476:1496	the thermal unfolding of A1	1476:1502	Glycosylation increases the hydrodynamic size of A1 and stabilizes the thermal unfolding of A1 without changing its equilibrium stability.
31479573	10	89	theme	conformational	1830:1843	arg1	dynamics					1845:1852	the conformational dynamics	1826:1852	the conformational dynamics of A1	1826:1858	CONCLUSIONS These studies invalidate the proposed inhibition through conformational suppression since glycosylation within these flanking sequences does not alter the native state stability or the conformational dynamics of A1.
31479573	1	90	theme	C-terminal	252:261	arg1	sequences					272:280	the N-terminal and C-terminal flanking sequences	233:280	the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop	233:321	BACKGROUND A molecular basis for von Willebrand factor (VWF) self-inhibition has been proposed by which the N-terminal and C-terminal flanking sequences of the globular A1 domain disulfide loop bind to and suppress the conformational dynamics of A1.
31142619	0	0	theme	Toxoplasma	91:100	arg1	gondii					102:107	the Intracellular Parasite Toxoplasma gondii	64:107	the Intracellular Parasite Toxoplasma gondii	64:107	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	6	1	theme	esterase-ester	1069:1082	arg1	approach					1100:1107	this esterase-ester click chemistry approach	1064:1107	this esterase-ester click chemistry approach	1064:1107	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	5	2	theme	porcine	915:921	arg1	esterase					929:936	porcine liver esterase	915:936	porcine liver esterase produced in the parasites but not in the host cells	915:988	We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells.
31142619	2	3	from	form	301:304	arg1	system					338:343	the central nervous system	318:343	the central nervous system	318:343	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	1	4	theme	human	254:258	arg1	population					260:269	the human population	250:269	the human population	250:269	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	0	5	theme	Parasite	82:89	arg1	gondii					102:107	the Intracellular Parasite Toxoplasma gondii	64:107	the Intracellular Parasite Toxoplasma gondii	64:107	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	6	6	theme	cells	1351:1355	arg1	presence					1299:1306	the presence	1295:1306	the presence of multiple membranes and surrounding host cells	1295:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	5	7	theme	liver	923:927	arg1	esterase					929:936	porcine liver esterase	915:936	porcine liver esterase produced in the parasites but not in the host cells	915:988	We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells.
31142619	7	8	from	enzyme	1492:1497	arg1	manner					1519:1524	a stage-specific manner	1502:1524	a stage-specific manner	1502:1524	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	1	9	theme	population	260:269	arg1	third					241:245	third	241:245	third	241:245	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	7	10	theme	host	1544:1547	arg1	biology					1554:1560	host cell biology	1544:1560	host cell biology	1544:1560	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	6	11	theme	host	1346:1349	arg1	cells					1351:1355	surrounding host cells	1334:1355	surrounding host cells	1334:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	3	12	theme	existing	508:515	arg1	methods					536:542	the existing metabolic labeling methods	504:542	the existing metabolic labeling methods	504:542	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	6	13	theme	intracellular	1236:1248	arg1	parasites					1250:1258	intracellular parasites	1236:1258	intracellular parasites	1236:1258	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	2	14	from	cysts	309:313	arg1	system					338:343	the central nervous system	318:343	the central nervous system	318:343	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	6	15	theme	proof-of-concept	995:1010	arg1	study					1012:1016	Our proof-of-concept study	991:1016	Our proof-of-concept study	991:1016	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	6	16	from	delivery	1127:1134	arg1	manner.IMPORTANCE					1175:1191	a stage-specific manner.IMPORTANCE	1158:1191	a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells	1158:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	8	17	theme	valuable	1586:1593	arg1	tool					1595:1598	a valuable tool	1584:1598	a valuable tool for studying many intracellular parasites	1584:1640	This system provides a valuable tool for studying many intracellular parasites.
31142619	5	18	theme	host	979:982	arg1	cells					984:988	the host cells	975:988	the host cells	975:988	We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells.
31142619	2	19	from	system	338:343	arg1	form					301:304	the form	297:304	the form of cysts in the central nervous system	297:343	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	4	20	theme	pair	761:764	arg1	system					766:771	a specific esterase-ester pair system	735:771	a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites	735:846	In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites.
31142619	4	21	theme	click	714:718	arg1	chemistry					720:728	Cu(I)-catalyzed bioorthogonal click chemistry	684:728	Cu(I)-catalyzed bioorthogonal click chemistry	684:728	In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites.
31142619	4	22	theme	bioorthogonal	700:712	arg1	chemistry					720:728	Cu(I)-catalyzed bioorthogonal click chemistry	684:728	Cu(I)-catalyzed bioorthogonal click chemistry	684:728	In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites.
31142619	3	23	gly	glycoproteins	602:614	arg1	glycoproteins					602:614	intracellular parasite glycoproteins	579:614	intracellular parasite glycoproteins	579:614	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	3	24	theme	labeling	527:534	arg1	methods					536:542	the existing metabolic labeling methods	504:542	the existing metabolic labeling methods	504:542	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	1	25	theme	obligate	176:183	arg1	parasite					199:206	an obligate intracellular parasite	173:206	an obligate intracellular parasite that chronically infects up to a third of the human population	173:269	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	1	25	theme	obligate	176:183	arg1	gondii					163:168	Toxoplasma gondii	152:168	Toxoplasma gondii	152:168	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	6	26	theme	membranes	1320:1328	arg1	presence					1299:1306	the presence	1295:1306	the presence of multiple membranes and surrounding host cells	1295:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	6	27	theme	Selective	1193:1201	arg1	delivery					1203:1210	Selective delivery	1193:1210	Selective delivery of small molecules into intracellular parasites	1193:1258	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	6	28	theme	small	1215:1219	arg1	molecules					1221:1229	small molecules	1215:1229	small molecules	1215:1229	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	6	29	theme	selective	1117:1125	arg1	delivery					1127:1134	the selective delivery	1113:1134	the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells	1113:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	1	30	theme	intracellular	185:197	arg1	parasite					199:206	an obligate intracellular parasite	173:206	an obligate intracellular parasite that chronically infects up to a third of the human population	173:269	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	1	30	theme	intracellular	185:197	arg1	gondii					163:168	Toxoplasma gondii	152:168	Toxoplasma gondii	152:168	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	6	31	from	molecules	1145:1153	arg1	manner.IMPORTANCE					1175:1191	a stage-specific manner.IMPORTANCE	1158:1191	a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells	1158:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	7	32	theme	stage-specific	1504:1517	arg1	manner					1519:1524	a stage-specific manner	1502:1524	a stage-specific manner	1502:1524	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	6	33	theme	multiple	1311:1318	arg1	membranes					1320:1328	multiple membranes	1311:1328	multiple membranes	1311:1328	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	6	34	theme	approach	1100:1107	arg1	feasibility					1035:1045	the feasibility	1031:1045	the feasibility	1031:1045	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	6	34	theme	approach	1100:1107	arg1	potential					1051:1059	potential	1051:1059	potential	1051:1059	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	0	35	theme	Stage-Specific	0:13	arg1	Delivery					29:36	Stage-Specific and Selective Delivery	0:36	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii	0:107	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	8	36	theme	many	1613:1616	arg1	parasites					1632:1640	many intracellular parasites	1613:1640	many intracellular parasites	1613:1640	This system provides a valuable tool for studying many intracellular parasites.
31142619	2	37	theme	cysts	309:313	arg1	form					301:304	the form	297:304	the form of cysts in the central nervous system	297:343	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	3	38	theme	cyst	424:427	arg1	wall					429:432	The cyst wall	420:432	The cyst wall	420:432	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	7	39	theme	intracellular	1424:1436	arg1	gondii					1459:1464	an intracellular parasite, Toxoplasma gondii	1421:1464	gondii	1459:1464	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	0	40	theme	Pair	136:139	arg1	Technique					141:149	an Esterase-Ester Pair Technique	118:149	an Esterase-Ester Pair Technique	118:149	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	4	41	theme	intracellular	824:836	arg1	parasites					838:846	the intracellular parasites	820:846	the intracellular parasites	820:846	In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites.
31142619	4	42	theme	esterase-ester	746:759	arg1	system					766:771	a specific esterase-ester pair system	735:771	a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites	735:846	In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites.
31142619	6	43	from	manner.IMPORTANCE	1175:1191	arg1	delivery					1127:1134	the selective delivery	1113:1134	the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells	1113:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	6	44	theme	click	1084:1088	arg1	approach					1100:1107	this esterase-ester click chemistry approach	1064:1107	this esterase-ester click chemistry approach	1064:1107	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	0	45	theme	Selective	19:27	arg1	Delivery					29:36	Stage-Specific and Selective Delivery	0:36	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii	0:107	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	0	46	theme	Esterase-Ester	121:134	arg1	Technique					141:149	an Esterase-Ester Pair Technique	118:149	an Esterase-Ester Pair Technique	118:149	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	3	47	theme	selective	557:565	arg1	labeling					567:574	selective labeling	557:574	selective labeling of intracellular parasite glycoproteins	557:614	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	2	48	theme	encephalitis	406:417	arg1	reactivation					378:389	the reactivation	374:389	the reactivation of toxoplasmic encephalitis	374:417	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	0	49	theme	Caged	41:45	arg1	Azidosugars					47:57	Caged Azidosugars	41:57	Caged Azidosugars	41:57	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	4	50	theme	-catalyzed	689:698	arg1	chemistry					720:728	Cu(I)-catalyzed bioorthogonal click chemistry	684:728	Cu(I)-catalyzed bioorthogonal click chemistry	684:728	In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites.
31142619	3	51	theme	glycoproteins	602:614	arg1	labeling					567:574	selective labeling	557:574	selective labeling of intracellular parasite glycoproteins	557:614	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	6	52	theme	chemistry	1090:1098	arg1	approach					1100:1107	this esterase-ester click chemistry approach	1064:1107	this esterase-ester click chemistry approach	1064:1107	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	2	53	theme	toxoplasmic	394:404	arg1	encephalitis					406:417	toxoplasmic encephalitis	394:417	toxoplasmic encephalitis	394:417	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	5	54	theme	α-cyclopropyl	870:882	arg1	GalNAz					893:898	α-cyclopropyl modified GalNAz	870:898	α-cyclopropyl modified GalNAz	870:898	We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells.
31142619	7	55	theme	parasite	1438:1445	arg1	gondii					1459:1464	an intracellular parasite, Toxoplasma gondii	1421:1464	gondii	1459:1464	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	3	56	link	O-linked	460:467	arg1	glycans					491:497	abundant O-linked N-acetylgalactosamine glycans	451:497	abundant O-linked N-acetylgalactosamine glycans	451:497	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	3	57	contain	have	446:449	arg1	wall					429:432	The cyst wall	420:432	The cyst wall	420:432	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	3	57	contain	have	446:449	arg2	glycans					491:497	abundant O-linked N-acetylgalactosamine glycans	451:497	abundant O-linked N-acetylgalactosamine glycans	451:497	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	3	58	theme	intracellular	579:591	arg1	glycoproteins					602:614	intracellular parasite glycoproteins	579:614	intracellular parasite glycoproteins	579:614	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	6	59	theme	small	1139:1143	arg1	molecules					1145:1153	small molecules	1139:1153	small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells	1139:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	3	60	theme	abundant	451:458	arg1	glycans					491:497	abundant O-linked N-acetylgalactosamine glycans	451:497	abundant O-linked N-acetylgalactosamine glycans	451:497	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	0	61	theme	Azidosugars	47:57	arg1	Delivery					29:36	Stage-Specific and Selective Delivery	0:36	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii	0:107	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	6	62	theme	surrounding	1334:1344	arg1	cells					1351:1355	surrounding host cells	1334:1355	surrounding host cells	1334:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	7	63	dep	gondii	1459:1464	arg1	Toxoplasma					1448:1457	an intracellular parasite, Toxoplasma gondii	1421:1464	Toxoplasma	1448:1457	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	3	64	theme	parasite	593:600	arg1	glycoproteins					602:614	intracellular parasite glycoproteins	579:614	intracellular parasite glycoproteins	579:614	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	2	65	theme	nervous	330:336	arg1	system					338:343	the central nervous system	318:343	the central nervous system	318:343	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	8	66	theme	intracellular	1618:1630	arg1	parasites					1632:1640	many intracellular parasites	1613:1640	many intracellular parasites	1613:1640	This system provides a valuable tool for studying many intracellular parasites.
31142619	6	67	theme	molecules	1221:1229	arg1	delivery					1203:1210	Selective delivery	1193:1210	Selective delivery of small molecules into intracellular parasites	1193:1258	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	3	68	theme	host	636:639	arg1	glycans					641:647	host glycans	636:647	host glycans	636:647	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	2	69	theme	central	322:328	arg1	system					338:343	the central nervous system	318:343	the central nervous system	318:343	The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis.
31142619	6	70	theme	molecules	1145:1153	arg1	delivery					1127:1134	the selective delivery	1113:1134	the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells	1113:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	7	71	theme	uncaging	1483:1490	arg1	enzyme					1492:1497	an uncaging enzyme	1480:1497	an uncaging enzyme in a stage-specific manner	1480:1524	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	6	72	dep	manner.IMPORTANCE	1175:1191	arg1	problematic					1276:1286	problematic	1276:1286	problematic	1276:1286	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	3	73	theme	glycans	641:647	arg1	labeling					624:631	labeling	624:631	labeling of host glycans	624:647	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	4	74	theme	specific	737:744	arg1	system					766:771	a specific esterase-ester pair system	735:771	a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites	735:846	In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites.
31142619	3	75	theme	N-acetylgalactosamine	469:489	arg1	glycans					491:497	abundant O-linked N-acetylgalactosamine glycans	451:497	abundant O-linked N-acetylgalactosamine glycans	451:497	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	6	76	theme	stage-specific	1160:1173	arg1	manner.IMPORTANCE					1175:1191	a stage-specific manner.IMPORTANCE	1158:1191	a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells	1158:1355	Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner.IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells.
31142619	3	77	theme	O-linked	460:467	arg1	glycans					491:497	abundant O-linked N-acetylgalactosamine glycans	451:497	abundant O-linked N-acetylgalactosamine glycans	451:497	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
31142619	0	78	theme	Intracellular	68:80	arg1	gondii					102:107	the Intracellular Parasite Toxoplasma gondii	64:107	the Intracellular Parasite Toxoplasma gondii	64:107	Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique.
31142619	7	79	theme	caged	1400:1404	arg1	molecules					1406:1414	caged molecules	1400:1414	caged molecules	1400:1414	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	1	80	theme	Toxoplasma	152:161	arg1	parasite					199:206	an obligate intracellular parasite	173:206	an obligate intracellular parasite that chronically infects up to a third of the human population	173:269	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	1	80	theme	Toxoplasma	152:161	arg1	gondii					163:168	Toxoplasma gondii	152:168	Toxoplasma gondii	152:168	Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population.
31142619	5	81	theme	modified	884:891	arg1	GalNAz					893:898	α-cyclopropyl modified GalNAz	870:898	α-cyclopropyl modified GalNAz	870:898	We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells.
31142619	7	82	theme	cell	1549:1552	arg1	biology					1554:1560	host cell biology	1544:1560	host cell biology	1544:1560	We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology.
31142619	3	83	theme	metabolic	517:525	arg1	methods					536:542	the existing metabolic labeling methods	504:542	the existing metabolic labeling methods	504:542	The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans.
30713024	5	0	theme	potent	718:723	arg1	tool					725:728	a potent tool	716:728	a potent tool to increase O-GlcNAc levels in several cell lines	716:778	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	5	0	theme	potent	718:723	arg1	Ac4GlcNAcF3					700:710	Ac4GlcNAcF3	700:710	Ac4GlcNAcF3	700:710	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	4	1	dep	in	504:505	arg1	vitro					507:511	vitro	507:511	vitro	507:511	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	8	2	theme	O-GlcNAc	1202:1209	arg1	study					1193:1197	the study	1189:1197	the study of O-GlcNAc	1189:1209	Thus, Ac4GlcNAcF3 represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O-GlcNAc.
30713024	1	3	located	found	178:182	arg1	Ser					187:189	Ser	187:189	Ser	187:189	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	3	located	found	178:182	arg1	Thr					194:196	Thr	194:196	Thr	194:196	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	3	located	found	178:182	arg2	N-acetylglucosamine					88:106	O-Linked N-acetylglucosamine	79:106	O-Linked N-acetylglucosamine (O-GlcNAc)	79:117	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	3	located	found	178:182	arg2	posttranslationalmonosaccaride-modification					134:176	an abundant posttranslationalmonosaccaride-modification	122:176	an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes	122:250	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	4	from	Thr	194:196	arg1	eukaryotes					241:250	most eukaryotes	236:250	most eukaryotes	236:250	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	3	5	theme	Cell	400:403	arg1	moleculars					421:430	Cell permeable small moleculars	400:430	Cell permeable small moleculars	400:430	Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels.
30713024	4	6	theme	substrate	513:521	arg1	screening					523:531	in vitro substrate screening	504:531	in vitro substrate screening	504:531	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	8	7	theme	safe	1124:1127	arg1	regulator					1138:1146	a safe and dual regulator	1122:1146	a safe and dual regulator	1122:1146	Thus, Ac4GlcNAcF3 represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O-GlcNAc.
30713024	6	8	theme	O-GlcNAc	864:871	arg1	levels					873:878	O-GlcNAc levels	864:878	O-GlcNAc levels	864:878	Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification.
30713024	1	9	from	Ser	187:189	arg1	eukaryotes					241:250	most eukaryotes	236:250	most eukaryotes	236:250	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	10	theme	O-Linked	79:86	arg1	posttranslationalmonosaccaride-modification					134:176	an abundant posttranslationalmonosaccaride-modification	122:176	an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes	122:250	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	10	theme	O-Linked	79:86	arg1	O-GlcNAc					109:116	O-GlcNAc	109:116	O-GlcNAc	109:116	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	10	theme	O-Linked	79:86	arg1	N-acetylglucosamine					88:106	O-Linked N-acetylglucosamine	79:106	O-Linked N-acetylglucosamine (O-GlcNAc)	79:117	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	8	11	theme	dual	1133:1136	arg1	regulator					1138:1146	a safe and dual regulator	1122:1146	a safe and dual regulator	1122:1146	Thus, Ac4GlcNAcF3 represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O-GlcNAc.
30713024	4	12	dep	sugar	594:598	arg1	mimic					600:604	mimic	600:604	mimic	600:604	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	1	13	theme	intracellular	210:222	arg1	proteins					224:231	intracellular proteins	210:231	intracellular proteins	210:231	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	6	14	theme	levels	873:878	arg1	significant					838:848	significant	838:848	significant	838:848	Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification.
30713024	5	15	theme	cell-permeable	633:646	arg1	Ac4GlcNAcF3					672:682	Ac4GlcNAcF3	672:682	Ac4GlcNAcF3	672:682	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	5	15	theme	cell-permeable	633:646	arg1	peracetylated-GlcNAcF3					648:669	cell-permeable peracetylated-GlcNAcF3	633:669	cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3)	633:683	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	3	16	theme	O-GlcNAc	473:480	arg1	levels					482:487	O-GlcNAc levels	473:487	O-GlcNAc levels	473:487	Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels.
30713024	0	17	theme	OGT-tolerated	16:28	arg1	Ac4GlcNAcF3					0:10	Ac4GlcNAcF3	0:10	Ac4GlcNAcF3	0:10	Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation.
30713024	0	17	theme	OGT-tolerated	16:28	arg1	regulator					48:56	an OGT-tolerated but OGA-resistant regulator	13:56	an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation	13:76	Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation.
30713024	5	18	theme	cell	769:772	arg1	lines					774:778	several cell lines	761:778	several cell lines	761:778	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	7	19	theme	O-GlcNAcF3	1009:1018	arg1	production					1020:1029	O-GlcNAcF3 production	1009:1029	O-GlcNAcF3 production	1009:1029	In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability.
30713024	2	20	theme	O-GlcNAc	341:348	arg1	stoichiometry					324:336	the stoichiometry	320:336	the stoichiometry of O-GlcNAc on proteins	320:360	The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function.
30713024	3	21	theme	small	415:419	arg1	moleculars					421:430	Cell permeable small moleculars	400:430	Cell permeable small moleculars	400:430	Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels.
30713024	5	22	with	experiments	616:626	arg1	Ac4GlcNAcF3					672:682	Ac4GlcNAcF3	672:682	Ac4GlcNAcF3	672:682	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	5	22	with	experiments	616:626	arg1	peracetylated-GlcNAcF3					648:669	cell-permeable peracetylated-GlcNAcF3	633:669	cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3)	633:683	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	6	23	theme	OGT-dependent	937:949	arg1	modification					951:962	an OGT-dependent modification	934:962	an OGT-dependent modification	934:962	Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification.
30713024	6	23	theme	OGT-dependent	937:949	arg1	O-GlcNAcF3					919:928	O-GlcNAcF3	919:928	O-GlcNAcF3	919:928	Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification.
30713024	1	24	dep	Ser	187:189	arg1	residues					198:205	residues	198:205	residues	198:205	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	7	25	theme	significant	1038:1048	arg1	effect					1050:1055	no significant effect	1035:1055	no significant effect	1035:1055	In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability.
30713024	1	26	theme	most	236:239	arg1	eukaryotes					241:250	most eukaryotes	236:250	most eukaryotes	236:250	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	0	27	theme	OGA-resistant	34:46	arg1	Ac4GlcNAcF3					0:10	Ac4GlcNAcF3	0:10	Ac4GlcNAcF3	0:10	Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation.
30713024	0	27	theme	OGA-resistant	34:46	arg1	regulator					48:56	an OGT-tolerated but OGA-resistant regulator	13:56	an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation	13:76	Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation.
30713024	1	28	theme	proteins	224:231	arg1	Ser					187:189	Ser	187:189	Ser	187:189	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	28	theme	proteins	224:231	arg1	Thr					194:196	Thr	194:196	Thr	194:196	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	4	29	theme	OGT-accepted	563:574	arg1	GlcNAcF3					548:555	GlcNAcF3	548:555	GlcNAcF3	548:555	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	4	29	theme	OGT-accepted	563:574	arg1	sugar					594:598	an OGT-accepted but OGA-resistant sugar	560:598	an OGT-accepted but OGA-resistant sugar mimic	560:604	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	4	30	theme	in	504:505	arg1	screening					523:531	in vitro substrate screening	504:531	in vitro substrate screening	504:531	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	3	31	theme	permeable	405:413	arg1	moleculars					421:430	Cell permeable small moleculars	400:430	Cell permeable small moleculars	400:430	Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels.
30713024	5	32	theme	O-GlcNAc	742:749	arg1	levels					751:756	O-GlcNAc levels	742:756	O-GlcNAc levels in several cell lines	742:778	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	2	33	theme	dynamic	257:263	arg1	nature					265:270	The dynamic nature	253:270	The dynamic nature of O-GlcNAc	253:282	The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function.
30713024	3	34	theme	invaluable	444:453	arg1	tools					455:459	invaluable tools	444:459	invaluable tools	444:459	Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels.
30713024	4	35	theme	OGA-resistant	580:592	arg1	GlcNAcF3					548:555	GlcNAcF3	548:555	GlcNAcF3	548:555	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	4	35	theme	OGA-resistant	580:592	arg1	sugar					594:598	an OGT-accepted but OGA-resistant sugar	560:598	an OGT-accepted but OGA-resistant sugar mimic	560:604	Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic.
30713024	1	36	theme	abundant	125:132	arg1	posttranslationalmonosaccaride-modification					134:176	an abundant posttranslationalmonosaccaride-modification	122:176	an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes	122:250	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	1	36	theme	abundant	125:132	arg1	N-acetylglucosamine					88:106	O-Linked N-acetylglucosamine	79:106	O-Linked N-acetylglucosamine (O-GlcNAc)	79:117	O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes.
30713024	7	37	theme	toxic	987:991	arg1	assay					993:997	cellular toxic assay	978:997	cellular toxic assay confirmed O-GlcNAcF3 production	978:1029	In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability.
30713024	5	38	theme	Cellular	607:614	arg1	experiments					616:626	Cellular experiments	607:626	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3)	607:683	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	7	39	theme	cell	1060:1063	arg1	proliferation					1065:1077	cell proliferation	1060:1077	cell proliferation	1060:1077	In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability.
30713024	5	40	theme	several	761:767	arg1	lines					774:778	several cell lines	761:778	several cell lines	761:778	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30713024	2	41	from	stoichiometry	324:336	arg1	proteins					353:360	proteins	353:360	proteins	353:360	The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function.
30713024	7	42	contain	has	1031:1033	arg2	effect					1050:1055	no significant effect	1035:1055	no significant effect	1035:1055	In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability.
30713024	7	42	contain	has	1031:1033	arg1	assay					993:997	cellular toxic assay	978:997	cellular toxic assay confirmed O-GlcNAcF3 production	978:1029	In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability.
30713024	6	43	theme	Ac4GlcNAcF3	885:895	arg1	treatment					897:905	Ac4GlcNAcF3 treatment	885:905	Ac4GlcNAcF3 treatment	885:905	Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification.
30713024	7	44	theme	cellular	978:985	arg1	assay					993:997	cellular toxic assay	978:997	cellular toxic assay confirmed O-GlcNAcF3 production	978:1029	In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability.
30713024	2	45	theme	O-GlcNAc	275:282	arg1	nature					265:270	The dynamic nature	253:270	The dynamic nature of O-GlcNAc	253:282	The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function.
30713024	6	46	theme	NIH3T3	790:795	arg1	cells					797:801	NIH3T3 cells	790:801	NIH3T3 cells interfered with OGT (siOGT)	790:829	Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification.
30713024	5	47	from	levels	751:756	arg1	lines					774:778	several cell lines	761:778	several cell lines	761:778	Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines.
30514763	2	0	theme	immune	388:393	arg1	responses					395:403	immune responses	388:403	immune responses of many eukaryotic parasites	388:432	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	8	1	dep	findings	1505:1512	arg1	contrast					1484:1491	contrast	1484:1491	contrast	1484:1491	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	8	2	from	dispensable	1535:1545	arg1	tachyzoites					1560:1570	T. gondii tachyzoites	1550:1570	T. gondii tachyzoites	1550:1570	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	3	3	theme	T.	571:572	arg1	adhesin					560:566	a motility-associated adhesin	538:566	a motility-associated adhesin of T. gondii	538:579	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	3	theme	T.	571:572	arg1	protein					520:526	micronemal protein 2	509:528	micronemal protein 2 (MIC2)	509:535	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	6	4	theme	parasite	1253:1260	arg1	proteome					1262:1269	the wider parasite proteome	1243:1269	the wider parasite proteome	1243:1269	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	2	5	theme	Protein	308:314	arg1	glycosylation					316:328	Protein glycosylation	308:328	Protein glycosylation	308:328	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	6	6	theme	TgPOFUT2	1177:1184	arg1	loss					1169:1172	loss	1169:1172	loss of TgPOFUT2 in T. gondii	1169:1197	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	8	7	from	tachyzoites	1560:1570	arg1	dispensable					1535:1545	dispensable	1535:1545	dispensable	1535:1545	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	7	8	theme	TgPOFUT2	1391:1398	arg1	absence					1380:1386	absence	1380:1386	absence	1380:1386	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	7	8	theme	TgPOFUT2	1391:1398	arg1	presence					1368:1375	presence	1368:1375	presence	1368:1375	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	4	9	theme	affinity-purified	649:665	arg1	MIC2					667:670	affinity-purified MIC2 and MS/MS analysis	649:689	MIC2	667:670	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	8	10	dep	T.	1580:1581	arg1	gondii					1583:1588	gondii	1583:1588	gondii	1583:1588	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	2	11	theme	important	339:347	arg1	role					349:352	an important role	336:352	an important role	336:352	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	1	12	theme	birth	236:240	arg1	defects					242:248	congenital birth defects	225:248	congenital birth defects	225:248	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	13	from	defects	242:248	arg1	individuals					280:290	immunocompromised individuals	262:290	immunocompromised individuals	262:290	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	6	14	theme	MIC2	1227:1230	arg1	levels					1232:1237	MIC2 levels	1227:1237	MIC2 levels	1227:1237	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	3	15	theme	thrombospondin	606:619	arg1	repeat					621:626	thrombospondin repeat	606:626	highly glycosylated thrombospondin repeat (TSR) domains	586:640	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	15	theme	thrombospondin	606:619	arg1	TSR					629:631	TSR	629:631	TSR	629:631	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	8	16	dep	indicate	1416:1423	arg1	that					1425:1428	that	1425:1428	that	1425:1428	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	4	17	theme	digestion	712:720	arg1	assays					722:727	enzymatic digestion assays	702:727	enzymatic digestion assays	702:727	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	1	18	theme	intracellular	179:191	arg1	parasite					204:211	a ubiquitous, obligate intracellular eukaryotic parasite	156:211	parasite	204:211	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	18	theme	intracellular	179:191	arg1	gondii					146:151	Toxoplasma gondii	135:151	Toxoplasma gondii	135:151	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	4	19	theme	O-linked	781:788	arg1	sites					804:808	three O-linked glycosylation sites	775:808	three O-linked glycosylation sites	775:808	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	0	20	theme	gondii	106:111	arg1	infection					124:132	Toxoplasma gondii tachyzoite infection	95:132	Toxoplasma gondii tachyzoite infection	95:132	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	4	21	from	sites	874:878	arg1	occupancy					839:847	>95% occupancy	834:847	>95% occupancy at these O-glycosylation sites	834:878	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	6	22	theme	motility-associated	1084:1102	arg1	adhesins					1104:1111	motility-associated adhesins	1084:1111	motility-associated adhesins	1084:1111	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	3	23	contain	has	582:584	arg2	domains					634:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	23	contain	has	582:584	arg1	protein					520:526	micronemal protein 2	509:528	micronemal protein 2 (MIC2)	509:535	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	23	contain	has	582:584	arg1	MIC2					531:534	MIC2	531:534	MIC2	531:534	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	23	contain	has	582:584	arg1	adhesin					560:566	a motility-associated adhesin	538:566	a motility-associated adhesin of T. gondii	538:579	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	2	24	theme	parasites	424:432	arg1	responses					395:403	immune responses	388:403	immune responses of many eukaryotic parasites	388:432	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	0	25	theme	Protein	0:6	arg1	O-glycosylation					40:54	Protein O-fucosyltransferase 2-mediated O-glycosylation	0:54	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2	0:74	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	5	26	theme	protein	942:948	arg1	O-fucosyltransferase					950:969	a protein O-fucosyltransferase 2 homolog (TgPOFUT2)	940:990	a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene	940:1023	We found that addition of O-glycans to MIC2 is mediated by a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene.
30514763	7	27	from	presence	1368:1375	arg1	similar					1353:1359	similar	1353:1359	similar	1353:1359	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	7	28	theme	tachyzoite	1320:1329	arg1	invasion					1331:1338	tachyzoite invasion	1320:1338	tachyzoite invasion	1320:1338	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	2	29	theme	vaccine	468:474	arg1	design					476:481	vaccine design	468:481	vaccine design	468:481	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	0	30	theme	2-mediated	29:38	arg1	O-glycosylation					40:54	Protein O-fucosyltransferase 2-mediated O-glycosylation	0:54	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2	0:74	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	7	31	from	absence	1380:1386	arg1	similar					1353:1359	similar	1353:1359	similar	1353:1359	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	5	32	dep	O-fucosyltransferase	950:969	arg1	TgPOFUT2					982:989	TgPOFUT2	982:989	TgPOFUT2	982:989	We found that addition of O-glycans to MIC2 is mediated by a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene.
30514763	5	32	dep	O-fucosyltransferase	950:969	arg1	homolog					973:979	2 homolog	971:979	a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene	940:1023	We found that addition of O-glycans to MIC2 is mediated by a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene.
30514763	8	33	theme	T.	1550:1551	arg1	tachyzoites					1560:1570	T. gondii tachyzoites	1550:1570	T. gondii tachyzoites	1550:1570	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	4	34	theme	>95	834:836	arg1	%					837:837	%	837:837	%	837:837	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	7	35	with	Consistent	1272:1281	arg1	this					1288:1291	this	1288:1291	this	1288:1291	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	6	36	theme	POFUT2	1038:1043	arg1	homologs					1045:1052	POFUT2 homologs	1038:1052	POFUT2 homologs	1038:1052	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	8	37	from	findings	1505:1512	arg1	study					1525:1529	another study	1517:1529	another study	1517:1529	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	0	38	theme	adhesin	63:69	arg1	MIC2					71:74	the adhesin MIC2	59:74	the adhesin MIC2	59:74	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	0	39	gly	O-glycosylation	40:54	arg1	MIC2					71:74	the adhesin MIC2	59:74	the adhesin MIC2	59:74	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	6	40	theme	apicomplexan	1145:1156	arg1	parasites					1158:1166	other apicomplexan parasites	1139:1166	other apicomplexan parasites	1139:1166	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	3	41	theme	micronemal	509:518	arg1	protein					520:526	micronemal protein 2	509:528	micronemal protein 2 (MIC2)	509:535	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	41	theme	micronemal	509:518	arg1	MIC2					531:534	MIC2	531:534	MIC2	531:534	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	41	theme	micronemal	509:518	arg1	adhesin					560:566	a motility-associated adhesin	538:566	a motility-associated adhesin of T. gondii	538:579	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	8	42	theme	O-glycosylates	1439:1452	arg1	MIC2					1454:1457	TgPOFUT2 O-glycosylates MIC2	1430:1457	TgPOFUT2 O-glycosylates MIC2	1430:1457	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	2	43	theme	many	408:411	arg1	parasites					424:432	many eukaryotic parasites	408:432	many eukaryotic parasites	408:432	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	1	44	theme	immunocompromised	262:278	arg1	individuals					280:290	immunocompromised individuals	262:290	immunocompromised individuals	262:290	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	5	45	theme	TGGT1_273550	1007:1018	arg1	gene					1020:1023	the TGGT1_273550 gene	1003:1023	the TGGT1_273550 gene	1003:1023	We found that addition of O-glycans to MIC2 is mediated by a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene.
30514763	6	46	theme	host	1121:1124	arg1	infection					1126:1134	host infection	1121:1134	host infection in other apicomplexan parasites	1121:1166	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	6	47	contain	had	1199:1201	arg2	impact					1217:1222	only a modest impact	1203:1222	only a modest impact	1203:1222	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	6	47	contain	had	1199:1201	arg1	loss					1169:1172	loss	1169:1172	loss of TgPOFUT2 in T. gondii	1169:1197	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	4	48	gly	glycosylation	790:802	arg2	sites					804:808	three O-linked glycosylation sites	775:808	three O-linked glycosylation sites	775:808	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	4	48	gly	glycosylation	790:802	arg2	three					775:779	three	775:779	three	775:779	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	2	49	theme	responses	395:403	arg1	evasion					377:383	evasion	377:383	evasion	377:383	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	2	49	theme	responses	395:403	arg1	infectivity					361:371	infectivity	361:371	infectivity	361:371	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	5	50	theme	O-glycans	907:915	arg1	addition					895:902	addition	895:902	addition of O-glycans to MIC2	895:923	We found that addition of O-glycans to MIC2 is mediated by a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene.
30514763	3	51	theme	motility-associated	540:558	arg1	adhesin					560:566	a motility-associated adhesin	538:566	a motility-associated adhesin of T. gondii	538:579	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	51	theme	motility-associated	540:558	arg1	protein					520:526	micronemal protein 2	509:528	micronemal protein 2 (MIC2)	509:535	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	1	52	theme	eukaryotic	193:202	arg1	parasite					204:211	a ubiquitous, obligate intracellular eukaryotic parasite	156:211	parasite	204:211	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	52	theme	eukaryotic	193:202	arg1	gondii					146:151	Toxoplasma gondii	135:151	Toxoplasma gondii	135:151	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	4	53	theme	MS/MS	676:680	arg1	analysis					682:689	affinity-purified MIC2 and MS/MS analysis	649:689	analysis	682:689	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	6	54	theme	wider	1247:1251	arg1	proteome					1262:1269	the wider parasite proteome	1243:1269	the wider parasite proteome	1243:1269	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	4	55	theme	O-glycosylation	858:872	arg1	sites					874:878	these O-glycosylation sites	852:878	these O-glycosylation sites	852:878	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	1	56	from	blindness	297:305	arg1	individuals					280:290	immunocompromised individuals	262:290	immunocompromised individuals	262:290	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	57	theme	congenital	225:234	arg1	defects					242:248	congenital birth defects	225:248	congenital birth defects	225:248	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	3	58	theme	repeat	621:626	arg1	domains					634:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	4	59	gly	O-glycosylation	858:872	arg2	sites					874:878	these O-glycosylation sites	852:878	these O-glycosylation sites	852:878	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	3	60	gly	glycosylated	593:604	arg1	domains					634:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	3	61	theme	glycosylated	593:604	arg1	domains					634:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	highly glycosylated thrombospondin repeat (TSR) domains	586:640	Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains.
30514763	1	62	theme	Toxoplasma	135:144	arg1	gondii					146:151	Toxoplasma gondii	135:151	Toxoplasma gondii	135:151	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	62	theme	Toxoplasma	135:144	arg1	parasite					204:211	a ubiquitous, obligate intracellular eukaryotic parasite	156:211	parasite	204:211	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	63	from	disease	251:257	arg1	individuals					280:290	immunocompromised individuals	262:290	immunocompromised individuals	262:290	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	8	64	dep	that	1425:1428	arg1	MIC2					1454:1457	TgPOFUT2 O-glycosylates MIC2	1430:1457	TgPOFUT2 O-glycosylates MIC2	1430:1457	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	8	64	dep	that	1425:1428	arg1	dispensable					1535:1545	dispensable	1535:1545	dispensable	1535:1545	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	7	65	dep	presence	1368:1375	arg1	the					1364:1366	the	1364:1366	the	1364:1366	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	6	66	theme	modest	1210:1215	arg1	impact					1217:1222	only a modest impact	1203:1222	only a modest impact	1203:1222	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	4	67	link	O-linked	781:788	arg1	sites					804:808	three O-linked glycosylation sites	775:808	three O-linked glycosylation sites	775:808	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	1	68	theme	ubiquitous	158:167	arg1	parasite					204:211	a ubiquitous, obligate intracellular eukaryotic parasite	156:211	parasite	204:211	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	68	theme	ubiquitous	158:167	arg1	gondii					146:151	Toxoplasma gondii	135:151	Toxoplasma gondii	135:151	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	8	69	theme	previous	1496:1503	arg1	findings					1505:1512	previous findings	1496:1512	previous findings in another study	1496:1529	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	4	70	theme	enzymatic	702:710	arg1	assays					722:727	enzymatic digestion assays	702:727	enzymatic digestion assays	702:727	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	0	71	theme	Toxoplasma	95:104	arg1	infection					124:132	Toxoplasma gondii tachyzoite infection	95:132	Toxoplasma gondii tachyzoite infection	95:132	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	1	72	theme	obligate	170:177	arg1	parasite					204:211	a ubiquitous, obligate intracellular eukaryotic parasite	156:211	parasite	204:211	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	1	72	theme	obligate	170:177	arg1	gondii					146:151	Toxoplasma gondii	135:151	Toxoplasma gondii	135:151	Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness.
30514763	0	73	theme	tachyzoite	113:122	arg1	infection					124:132	Toxoplasma gondii tachyzoite infection	95:132	Toxoplasma gondii tachyzoite infection	95:132	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	7	74	from	similar	1353:1359	arg1	absence					1380:1386	absence	1380:1386	absence	1380:1386	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	7	74	from	similar	1353:1359	arg1	presence					1368:1375	presence	1368:1375	presence	1368:1375	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	4	75	theme	glycosylation	790:802	arg1	sites					804:808	three O-linked glycosylation sites	775:808	three O-linked glycosylation sites	775:808	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	0	76	theme	O-fucosyltransferase	8:27	arg1	O-glycosylation					40:54	Protein O-fucosyltransferase 2-mediated O-glycosylation	0:54	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2	0:74	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	2	77	dep	infectivity	361:371	arg1	the					357:359	the	357:359	the	357:359	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	6	78	from	loss	1169:1172	arg1	T.					1189:1190	T.	1189:1190	T.	1189:1190	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	2	79	theme	eukaryotic	413:422	arg1	parasites					424:432	many eukaryotic parasites	408:432	many eukaryotic parasites	408:432	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	7	80	theme	plaque	1299:1304	arg1	formation					1306:1314	plaque formation	1299:1314	plaque formation	1299:1314	Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2.
30514763	8	81	theme	gondii	1553:1558	arg1	tachyzoites					1560:1570	T. gondii tachyzoites	1550:1570	T. gondii tachyzoites	1550:1570	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	2	82	theme	great	449:453	arg1	relevance					455:463	great relevance	449:463	great relevance	449:463	Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design.
30514763	0	83	theme	MIC2	71:74	arg1	O-glycosylation					40:54	Protein O-fucosyltransferase 2-mediated O-glycosylation	0:54	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2	0:74	Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.
30514763	8	84	theme	T.	1580:1581	arg1	infectivity					1590:1600	T. gondii infectivity	1580:1600	T. gondii infectivity	1580:1600	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	4	85	theme	%	837:837	arg1	occupancy					839:847	>95% occupancy	834:847	>95% occupancy at these O-glycosylation sites	834:878	Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites.
30514763	6	86	theme	other	1139:1143	arg1	parasites					1158:1166	other apicomplexan parasites	1139:1166	other apicomplexan parasites	1139:1166	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30514763	8	87	theme	TgPOFUT2	1430:1437	arg1	MIC2					1454:1457	TgPOFUT2 O-glycosylates MIC2	1430:1457	TgPOFUT2 O-glycosylates MIC2	1430:1457	These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.
30514763	6	88	from	infection	1126:1134	arg1	parasites					1158:1166	other apicomplexan parasites	1139:1166	other apicomplexan parasites	1139:1166	Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome.
30250045	8	0	gly	disialylated	1163:1174	arg1	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	0	gly	disialylated	1163:1174	arg1	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	0	gly	disialylated	1163:1174	arg1	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	1	theme	core	1176:1179	arg1	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	1	theme	core	1176:1179	arg1	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	1	theme	core	1176:1179	arg1	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	5	2	theme	glycosylphosphatidylinositol-anchor	673:707	arg1	proteins					709:716	candidate epitope-fused glycosylphosphatidylinositol-anchor proteins	649:716	candidate epitope-fused glycosylphosphatidylinositol-anchor proteins	649:716	We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins.
30250045	8	3	theme	Mass	993:996	arg1	analysis					1011:1018	Mass spectrometry analysis	993:1018	Mass spectrometry analysis	993:1018	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	4	theme	glycan-modified	1192:1206	arg1	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	4	theme	glycan-modified	1192:1206	arg1	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	4	theme	glycan-modified	1192:1206	arg1	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	7	5	theme	SKxPSxVS	918:925	arg1	essential					959:967	essential	959:967	essential	959:967	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	7	5	theme	SKxPSxVS	918:925	arg1	sequence					927:934	the SKxPSxVS sequence	914:934	the SKxPSxVS sequence within the epitope	914:953	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	9	6	theme	similar	1343:1349	arg1	modification					1358:1369	a similar glycan modification	1341:1369	a similar glycan modification	1341:1369	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	9	7	theme	glycan	1351:1356	arg1	modification					1358:1369	a similar glycan modification	1341:1369	a similar glycan modification	1341:1369	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	8	8	theme	peptides	1067:1074	arg1	analysis					1011:1018	Mass spectrometry analysis	993:1018	Mass spectrometry analysis	993:1018	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	8	theme	peptides	1067:1074	arg1	analysis					1039:1046	lectin binding analysis	1024:1046	lectin binding analysis	1024:1046	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	1	9	theme	sialylated	189:198	arg1	homolog					212:218	the sialylated protein HEG homolog 1	185:220	the sialylated protein HEG homolog 1 (HEG1)	185:227	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	1	9	theme	sialylated	189:198	arg1	HEG1					223:226	HEG1	223:226	HEG1	223:226	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	0	10	theme	membrane	118:125	arg1	HEG1					135:138	a mucin-like membrane protein HEG1	105:138	a mucin-like membrane protein HEG1	105:138	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	4	11	theme	present	539:545	arg1	study					547:551	the present study	535:551	the present study	535:551	In the present study, we investigated the epitope of SKM9-2.
30250045	10	12	theme	specific	1505:1512	arg1	region					1514:1519	the specific region	1501:1519	the specific region of HEG1	1501:1527	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	5	13	theme	SKM9-2	620:625	arg1	binding					609:615	the binding	605:615	the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins	605:716	We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins.
30250045	0	14	theme	mucin-like	107:116	arg1	HEG1					135:138	a mucin-like membrane protein HEG1	105:138	a mucin-like membrane protein HEG1	105:138	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	10	15	gly	sialylated	1467:1476	arg1	modification					1485:1496	sialylated glycan modification	1467:1496	sialylated glycan modification	1467:1496	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	8	16	theme	binding	1031:1037	arg1	analysis					1039:1046	lectin binding analysis	1024:1046	lectin binding analysis	1024:1046	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	6	17	theme	O-glycosylated	762:775	arg1	893-SKSPSLVSLPT-903					785:803	893-SKSPSLVSLPT-903	785:803	893-SKSPSLVSLPT-903	785:803	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	6	17	theme	O-glycosylated	762:775	arg1	region					777:782	an O-glycosylated region	759:782	an O-glycosylated region	759:782	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	6	17	theme	O-glycosylated	762:775	arg1	epitope					723:729	The epitope	719:729	The epitope of SKM9-2	719:739	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	3	18	theme	malignant	508:516	arg1	mesothelioma					518:529	malignant mesothelioma	508:529	malignant mesothelioma	508:529	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30250045	3	19	theme	other	369:373	arg1	antibodies					375:384	other antibodies	369:384	other antibodies against current mesothelioma markers	369:421	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30250045	8	20	contain	contained	1149:1157	arg1	epitope					1102:1108	the SKM9-2 epitope	1091:1108	the SKM9-2 epitope	1091:1108	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	20	contain	contained	1149:1157	arg2	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	20	contain	contained	1149:1157	arg2	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	20	contain	contained	1149:1157	arg2	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	5	21	theme	truncated	630:638	arg1	HEG1					640:643	truncated HEG1	630:643	truncated HEG1	630:643	We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins.
30250045	10	22	theme	specific	1376:1383	arg1	detection					1385:1393	The specific detection	1372:1393	The specific detection of mesothelioma with SKM9-2	1372:1421	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	1	23	theme	protein	200:206	arg1	homolog					212:218	the sialylated protein HEG homolog 1	185:220	the sialylated protein HEG homolog 1 (HEG1)	185:227	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	1	23	theme	protein	200:206	arg1	HEG1					223:226	HEG1	223:226	HEG1	223:226	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	0	24	theme	protein	127:133	arg1	HEG1					135:138	a mucin-like membrane protein HEG1	105:138	a mucin-like membrane protein HEG1	105:138	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	8	25	theme	SKM9-2	1095:1100	arg1	epitope					1102:1108	the SKM9-2 epitope	1091:1108	the SKM9-2 epitope	1091:1108	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	9	26	theme	Neuraminidase	1244:1256	arg1	analysis					1268:1275	Neuraminidase treatment analysis	1244:1275	Neuraminidase treatment analysis	1244:1275	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	7	27	theme	simple	886:891	arg1	epitope					893:899	a simple epitope	884:899	a simple epitope in HEG1	884:907	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	1	28	theme	HEG	208:210	arg1	homolog					212:218	the sialylated protein HEG homolog 1	185:220	the sialylated protein HEG homolog 1 (HEG1)	185:227	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	1	28	theme	HEG	208:210	arg1	HEG1					223:226	HEG1	223:226	HEG1	223:226	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	7	29	theme	epitope	848:854	arg1	assay					835:839	An alanine scanning assay	815:839	An alanine scanning assay of the epitope	815:854	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	5	30	theme	candidate	649:657	arg1	proteins					709:716	candidate epitope-fused glycosylphosphatidylinositol-anchor proteins	649:716	candidate epitope-fused glycosylphosphatidylinositol-anchor proteins	649:716	We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins.
30250045	7	31	theme	SKM9-2	973:978	arg1	recognition					980:990	SKM9-2 recognition	973:990	SKM9-2 recognition	973:990	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	5	32	theme	epitope-fused	659:671	arg1	proteins					709:716	candidate epitope-fused glycosylphosphatidylinositol-anchor proteins	649:716	candidate epitope-fused glycosylphosphatidylinositol-anchor proteins	649:716	We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins.
30250045	8	33	theme	epitope	1059:1065	arg1	peptides					1067:1074	soluble epitope peptides	1051:1074	soluble epitope peptides	1051:1074	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	34	gly	glycosylated	1135:1146	arg1	epitope					1102:1108	the SKM9-2 epitope	1091:1108	the SKM9-2 epitope	1091:1108	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	34	gly	glycosylated	1135:1146	arg1	Ser897					1120:1125	Ser897	1120:1125	Ser897	1120:1125	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	34	gly	glycosylated	1135:1146	arg2	Ser897					1120:1125	Ser897	1120:1125	Ser897	1120:1125	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	3	35	theme	mesothelioma	402:413	arg1	markers					415:421	current mesothelioma markers	394:421	current mesothelioma markers	394:421	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30250045	10	36	theme	glycan	1478:1483	arg1	modification					1485:1496	sialylated glycan modification	1467:1496	sialylated glycan modification	1467:1496	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	7	37	from	epitope	893:899	arg1	HEG1					904:907	HEG1	904:907	HEG1	904:907	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	6	38	theme	SKM9-2	734:739	arg1	epitope					723:729	The epitope	719:729	The epitope of SKM9-2	719:739	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	6	38	theme	SKM9-2	734:739	arg1	region					777:782	an O-glycosylated region	759:782	an O-glycosylated region	759:782	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	10	39	theme	sialylated	1467:1476	arg1	modification					1485:1496	sialylated glycan modification	1467:1496	sialylated glycan modification	1467:1496	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	0	40	theme	mesothelioma-specific	18:38	arg1	epitope					51:57	mesothelioma-specific sialylated epitope	18:57	mesothelioma-specific sialylated epitope	18:57	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	10	41	theme	modification	1485:1496	arg1	recognition					1452:1462	the recognition	1448:1462	the recognition of sialylated glycan modification in the specific region of HEG1	1448:1527	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	4	42	theme	SKM9-2	585:590	arg1	epitope					574:580	the epitope	570:580	the epitope of SKM9-2	570:590	In the present study, we investigated the epitope of SKM9-2.
30250045	9	43	from	epitope	1301:1307	arg1	cells					1325:1329	mesothelioma cells	1312:1329	mesothelioma cells	1312:1329	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	2	44	theme	400 kDa	240:246	arg1	HEG1					230:233	HEG1	230:233	HEG1	230:233	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	2	44	theme	400 kDa	240:246	arg1	protein					268:274	a 400 kDa mucin-like membrane protein	238:274	a 400 kDa mucin-like membrane protein found on mesothelioma	238:296	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	3	45	theme	precise	473:479	arg1	detection					481:489	detection	481:489	detection	481:489	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30250045	0	46	theme	epitope	51:57	arg1	Identification					0:13	Identification	0:13	Identification of mesothelioma-specific sialylated epitope	0:57	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	10	47	from	recognition	1452:1462	arg1	region					1514:1519	the specific region	1501:1519	the specific region of HEG1	1501:1527	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	0	48	from	SKM9-2	95:100	arg1	HEG1					135:138	a mucin-like membrane protein HEG1	105:138	a mucin-like membrane protein HEG1	105:138	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	0	49	theme	sialylated	40:49	arg1	epitope					51:57	mesothelioma-specific sialylated epitope	18:57	mesothelioma-specific sialylated epitope	18:57	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	8	50	link	O-linked	1183:1190	arg1	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	50	link	O-linked	1183:1190	arg1	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	50	link	O-linked	1183:1190	arg1	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	0	51	theme	monoclonal	75:84	arg1	antibody					86:93	monoclonal antibody	75:93	monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1	75:138	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	8	52	theme	serine	1208:1213	arg1	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	52	theme	serine	1208:1213	arg1	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	52	theme	serine	1208:1213	arg1	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	53	theme	soluble	1051:1057	arg1	peptides					1067:1074	soluble epitope peptides	1051:1074	soluble epitope peptides	1051:1074	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	3	54	theme	mesothelioma	518:529	arg1	detection					481:489	detection	481:489	detection	481:489	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30250045	3	54	theme	mesothelioma	518:529	arg1	diagnosis					495:503	diagnosis	495:503	diagnosis	495:503	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30250045	7	55	theme	alanine	818:824	arg1	assay					835:839	An alanine scanning assay	815:839	An alanine scanning assay of the epitope	815:854	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	0	56	from	HEG1	135:138	arg1	SKM9-2					95:100	SKM9-2	95:100	SKM9-2	95:100	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	0	57	gly	sialylated	40:49	arg1	epitope					51:57	mesothelioma-specific sialylated epitope	18:57	mesothelioma-specific sialylated epitope	18:57	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	10	58	theme	mesothelioma	1398:1409	arg1	detection					1385:1393	The specific detection	1372:1393	The specific detection of mesothelioma with SKM9-2	1372:1421	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	7	59	theme	scanning	826:833	arg1	assay					835:839	An alanine scanning assay	815:839	An alanine scanning assay of the epitope	815:854	An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition.
30250045	1	60	gly	sialylated	189:198	arg1	homolog					212:218	the sialylated protein HEG homolog 1	185:220	the sialylated protein HEG homolog 1 (HEG1)	185:227	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	1	60	gly	sialylated	189:198	arg1	HEG1					223:226	HEG1	223:226	HEG1	223:226	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	6	61	gly	O-glycosylated	762:775	arg1	893-SKSPSLVSLPT-903					785:803	893-SKSPSLVSLPT-903	785:803	893-SKSPSLVSLPT-903	785:803	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	6	61	gly	O-glycosylated	762:775	arg1	region					777:782	an O-glycosylated region	759:782	an O-glycosylated region	759:782	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	6	61	gly	O-glycosylated	762:775	arg1	epitope					723:729	The epitope	719:729	The epitope of SKM9-2	719:739	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	1	62	theme	anti-mesothelioma	145:161	arg1	SKM9-2					167:172	The anti-mesothelioma mAb SKM9-2	141:172	The anti-mesothelioma mAb SKM9-2	141:172	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	10	63	with	detection	1385:1393	arg1	SKM9-2					1416:1421	SKM9-2	1416:1421	SKM9-2	1416:1421	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	3	64	dep	detection	481:489	arg1	the					469:471	the	469:471	the	469:471	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30250045	1	65	theme	mAb	163:165	arg1	SKM9-2					167:172	The anti-mesothelioma mAb SKM9-2	141:172	The anti-mesothelioma mAb SKM9-2	141:172	The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1).
30250045	8	66	theme	O-linked	1183:1190	arg1	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	66	theme	O-linked	1183:1190	arg1	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	66	theme	O-linked	1183:1190	arg1	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	2	67	located	found	276:280	arg2	HEG1					230:233	HEG1	230:233	HEG1	230:233	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	2	67	located	found	276:280	arg2	protein					268:274	a 400 kDa mucin-like membrane protein	238:274	a 400 kDa mucin-like membrane protein found on mesothelioma	238:296	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	2	67	located	found	276:280	arg1	mesothelioma					285:296	mesothelioma	285:296	mesothelioma	285:296	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	0	68	theme	SKM9-2	95:100	arg1	antibody					86:93	monoclonal antibody	75:93	monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1	75:138	Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
30250045	10	69	theme	HEG1	1524:1527	arg1	region					1514:1519	the specific region	1501:1519	the specific region of HEG1	1501:1527	The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
30250045	2	70	theme	membrane	259:266	arg1	HEG1					230:233	HEG1	230:233	HEG1	230:233	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	2	70	theme	membrane	259:266	arg1	protein					268:274	a 400 kDa mucin-like membrane protein	238:274	a 400 kDa mucin-like membrane protein found on mesothelioma	238:296	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	9	71	theme	mesothelioma	1312:1323	arg1	cells					1325:1329	mesothelioma cells	1312:1329	mesothelioma cells	1312:1329	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	8	72	theme	lectin	1024:1029	arg1	analysis					1039:1046	lectin binding analysis	1024:1046	lectin binding analysis	1024:1046	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	9	73	theme	treatment	1258:1266	arg1	analysis					1268:1275	Neuraminidase treatment analysis	1244:1275	Neuraminidase treatment analysis	1244:1275	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	8	74	theme	disialylated	1163:1174	arg1	Ser900					1236:1241	Ser900	1236:1241	Ser900	1236:1241	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	74	theme	disialylated	1163:1174	arg1	Ser893					1225:1230	Ser893	1225:1230	Ser893	1225:1230	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	8	74	theme	disialylated	1163:1174	arg1	residues					1215:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	two disialylated core 1 O-linked glycan-modified serine residues	1159:1222	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	2	75	theme	mucin-like	248:257	arg1	HEG1					230:233	HEG1	230:233	HEG1	230:233	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	2	75	theme	mucin-like	248:257	arg1	protein					268:274	a 400 kDa mucin-like membrane protein	238:274	a 400 kDa mucin-like membrane protein found on mesothelioma	238:296	HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma.
30250045	8	76	theme	spectrometry	998:1009	arg1	analysis					1011:1018	Mass spectrometry analysis	993:1018	Mass spectrometry analysis	993:1018	Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900.
30250045	6	77	from	region	777:782	arg1	HEG1					809:812	HEG1	809:812	HEG1	809:812	The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1.
30250045	9	78	contain	contained	1331:1339	arg1	epitope					1301:1307	the epitope	1297:1307	the epitope in mesothelioma cells	1297:1329	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	9	78	contain	contained	1331:1339	arg2	modification					1358:1369	a similar glycan modification	1341:1369	a similar glycan modification	1341:1369	Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification.
30250045	3	79	theme	current	394:400	arg1	markers					415:421	current mesothelioma markers	394:421	current mesothelioma markers	394:421	SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma.
30169771	9	0	theme	even	1452:1455	arg1	loss					1457:1460	even loss	1452:1460	even loss of one copy of the fly Gxylt shams	1452:1495	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	1	1	theme	multicellular	126:138	arg1	organisms					140:148	multicellular organisms	126:148	multicellular organisms	126:148	In multicellular organisms, glycosylation regulates various developmental signaling pathways including the Notch pathway.
30169771	8	2	theme	sensitized	1249:1258	arg1	backgrounds					1268:1278	sensitized genetic backgrounds	1249:1278	sensitized genetic backgrounds with decreased or increased Notch pathway components	1249:1331	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	10	3	theme	sensitized	1738:1747	arg1	backgrounds					1757:1767	sensitized genetic backgrounds	1738:1767	sensitized genetic backgrounds	1738:1767	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	5	4	theme	xylosyltransferase	897:914	arg1	CG11388					838:844	CG11388	838:844	CG11388	838:844	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	5	4	theme	xylosyltransferase	897:914	arg1	homolog					871:877	the Drosophila homolog	856:877	the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1)	856:925	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	9	5	theme	copy	1469:1472	arg1	loss					1457:1460	even loss	1452:1460	even loss of one copy of the fly Gxylt shams	1452:1495	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	8	6	theme	genetic	1204:1210	arg1	experiments					1224:1234	genetic interaction experiments	1204:1234	genetic interaction experiments	1204:1234	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	8	7	theme	decreased	1285:1293	arg1	components					1322:1331	decreased or increased Notch pathway components	1285:1331	decreased or increased Notch pathway components	1285:1331	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	5	8	theme	residues	744:751	arg1	contribution					710:721	the contribution	706:721	the contribution of the second xylose residues to Drosophila Notch signaling	706:781	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	10	9	theme	Delta-mediated	1634:1647	arg1	signaling					1655:1663	the Delta-mediated Notch signaling	1630:1663	the Delta-mediated Notch signaling in Drosophila	1630:1677	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	4	10	theme	both	689:692	arg1	loss					642:645	the loss	638:645	the loss of the first xylose, the second xylose or both	638:692	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	5	11	theme	Drosophila	756:765	arg1	signaling					773:781	Drosophila Notch signaling	756:781	Drosophila Notch signaling	756:781	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	2	12	theme	glycans	265:271	arg1	glycans					265:271	the O-linked glycans	252:271	the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	252:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	2	12	theme	glycans	265:271	arg1	oligosaccharide					405:419	the xylose-xylose-glucose-O oligosaccharide	377:419	the xylose-xylose-glucose-O oligosaccharide	377:419	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	2	12	theme	glycans	265:271	arg1	One					245:247	One	245:247	One	245:247	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	5	13	theme	human	882:886	arg1	xylosyltransferase					897:914	human xyloside xylosyltransferase 1	882:916	human xyloside xylosyltransferase 1 (XXYLT1)	882:925	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	5	13	theme	human	882:886	arg1	XXYLT1					919:924	XXYLT1	919:924	XXYLT1	919:924	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	8	14	theme	pathway	1314:1320	arg1	components					1322:1331	decreased or increased Notch pathway components	1285:1331	decreased or increased Notch pathway components	1285:1331	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	0	15	theme	Sensitized	0:9	arg1	backgrounds					19:29	Sensitized genetic backgrounds	0:29	Sensitized genetic backgrounds	0:29	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	2	16	link	O-linked	256:263	arg1	glycans					265:271	the O-linked glycans	252:271	the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	252:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	5	17	theme	second	730:735	arg1	residues					744:751	the second xylose residues	726:751	the second xylose residues	726:751	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	2	18	theme	growth	292:297	arg1	repeats					317:323	epidermal growth factor-like (EGF) repeats	282:323	epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	282:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	9	19	theme	Notch	1521:1525	arg1	activation					1527:1536	Delta-mediated Notch activation	1506:1536	Delta-mediated Notch activation	1506:1536	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	2	20	from	repeats	317:323	arg1	receptors					364:372	the Notch receptors	354:372	the Notch receptors	354:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	2	20	from	repeats	317:323	arg1	proteins					335:342	animal proteins	328:342	animal proteins including the Notch receptors	328:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	0	21	theme	repeat	65:70	arg1	xylosyltransferases					72:90	EGF repeat xylosyltransferases	61:90	EGF repeat xylosyltransferases	61:90	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	1	22	theme	various	175:181	arg1	pathways					207:214	various developmental signaling pathways	175:214	various developmental signaling pathways	175:214	In multicellular organisms, glycosylation regulates various developmental signaling pathways including the Notch pathway.
30169771	4	23	theme	xylose	562:567	arg1	residue					569:575	the first xylose residue	552:575	the first xylose residue to O-glucose	552:588	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	1	24	theme	signaling	197:205	arg1	pathways					207:214	various developmental signaling pathways	175:214	various developmental signaling pathways	175:214	In multicellular organisms, glycosylation regulates various developmental signaling pathways including the Notch pathway.
30169771	6	25	theme	second	1012:1017	arg1	xylose					1019:1024	the second xylose	1008:1024	the second xylose	1008:1024	Experiments in S2 cells indicated that similar to human XXYLT1, CG11388 can add the second xylose to xylose-glucose-O glycans.
30169771	0	26	theme	Notch	106:110	arg1	signaling					112:120	Drosophila Notch signaling	95:120	Drosophila Notch signaling	95:120	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	8	27	theme	Notch	1386:1390	arg1	activation					1372:1381	Delta-mediated activation	1357:1381	Delta-mediated activation of Notch	1357:1390	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	3	28	theme	xylosyltransferase	443:460	arg1	Shams					470:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams negatively regulates Notch signaling in specific contexts.
30169771	10	29	theme	Notch	1649:1653	arg1	signaling					1655:1663	the Delta-mediated Notch signaling	1630:1663	the Delta-mediated Notch signaling in Drosophila	1630:1677	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	7	30	theme	signaling	1184:1192	arg1	indicative					1156:1165	indicative	1156:1165	indicative	1156:1165	Flies lacking both copies of CG11388 (Xxylt) are viable and fertile and do not show gross phenotypes indicative of altered Notch signaling.
30169771	3	31	theme	Drosophila	422:431	arg1	Shams					470:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams negatively regulates Notch signaling in specific contexts.
30169771	10	32	theme	second	1684:1689	arg1	xylose					1691:1696	the second xylose	1680:1696	the second xylose	1680:1696	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	7	33	theme	altered	1170:1176	arg1	signaling					1184:1192	altered Notch signaling	1170:1192	altered Notch signaling	1170:1192	Flies lacking both copies of CG11388 (Xxylt) are viable and fertile and do not show gross phenotypes indicative of altered Notch signaling.
30169771	10	34	theme	genetic	1749:1755	arg1	backgrounds					1757:1767	sensitized genetic backgrounds	1738:1767	sensitized genetic backgrounds	1738:1767	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	3	35	theme	specific	516:523	arg1	contexts					525:532	specific contexts	516:532	specific contexts	516:532	Drosophila glucoside xylosyltransferase (Gxylt) Shams negatively regulates Notch signaling in specific contexts.
30169771	7	36	theme	indicative	1156:1165	arg1	phenotypes					1145:1154	gross phenotypes	1139:1154	gross phenotypes indicative of altered Notch signaling	1139:1192	Flies lacking both copies of CG11388 (Xxylt) are viable and fertile and do not show gross phenotypes indicative of altered Notch signaling.
30169771	0	37	theme	differential	38:49	arg1	roles					51:55	differential roles	38:55	differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling	38:120	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	3	38	theme	Gxylt	463:467	arg1	Shams					470:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams negatively regulates Notch signaling in specific contexts.
30169771	10	39	theme	fine-tuning	1704:1714	arg1	role					1716:1719	a fine-tuning role	1702:1719	a fine-tuning role only revealed in sensitized genetic backgrounds	1702:1767	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	7	40	theme	gross	1139:1143	arg1	phenotypes					1145:1154	gross phenotypes	1139:1154	gross phenotypes indicative of altered Notch signaling	1139:1192	Flies lacking both copies of CG11388 (Xxylt) are viable and fertile and do not show gross phenotypes indicative of altered Notch signaling.
30169771	4	41	theme	loss-of-function	595:610	arg1	phenotype					612:620	its loss-of-function phenotype	591:620	its loss-of-function phenotype	591:620	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	2	42	theme	Notch	358:362	arg1	receptors					364:372	the Notch receptors	354:372	the Notch receptors	354:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	4	43	theme	first	654:658	arg1	xylose					660:665	the first xylose	650:665	the first xylose	650:665	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	5	44	theme	biochemical	802:812	arg1	analysis					826:833	biochemical and genetic analysis	802:833	biochemical and genetic analysis	802:833	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	2	45	theme	xylose-xylose-glucose-O	381:403	arg1	glycans					265:271	the O-linked glycans	252:271	the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	252:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	2	45	theme	xylose-xylose-glucose-O	381:403	arg1	One					245:247	One	245:247	One	245:247	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	2	45	theme	xylose-xylose-glucose-O	381:403	arg1	oligosaccharide					405:419	the xylose-xylose-glucose-O oligosaccharide	377:419	the xylose-xylose-glucose-O oligosaccharide	377:419	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	9	46	theme	sensitized	1428:1437	arg1	backgrounds					1439:1449	such sensitized backgrounds	1423:1449	such sensitized backgrounds	1423:1449	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	6	47	theme	S2	943:944	arg1	cells					946:950	S2 cells	943:950	S2 cells	943:950	Experiments in S2 cells indicated that similar to human XXYLT1, CG11388 can add the second xylose to xylose-glucose-O glycans.
30169771	10	48	theme	first	1590:1594	arg1	xylose					1596:1601	the first xylose	1586:1601	the first xylose	1586:1601	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	6	49	from	Experiments	928:938	arg1	cells					946:950	S2 cells	943:950	S2 cells	943:950	Experiments in S2 cells indicated that similar to human XXYLT1, CG11388 can add the second xylose to xylose-glucose-O glycans.
30169771	2	50	theme	EGF	312:314	arg1	repeats					317:323	epidermal growth factor-like (EGF) repeats	282:323	epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	282:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	5	51	theme	xyloside	888:895	arg1	xylosyltransferase					897:914	human xyloside xylosyltransferase 1	882:916	human xyloside xylosyltransferase 1 (XXYLT1)	882:925	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	5	51	theme	xyloside	888:895	arg1	XXYLT1					919:924	XXYLT1	919:924	XXYLT1	919:924	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	10	52	theme	key	1611:1613	arg1	role					1615:1618	a key role	1609:1618	a key role	1609:1618	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	8	53	theme	genetic	1260:1266	arg1	backgrounds					1268:1278	sensitized genetic backgrounds	1249:1278	sensitized genetic backgrounds with decreased or increased Notch pathway components	1249:1331	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	5	54	theme	xylose	737:742	arg1	residues					744:751	the second xylose residues	726:751	the second xylose residues	726:751	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	2	55	theme	animal	328:333	arg1	receptors					364:372	the Notch receptors	354:372	the Notch receptors	354:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	2	55	theme	animal	328:333	arg1	proteins					335:342	animal proteins	328:342	animal proteins including the Notch receptors	328:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	5	56	theme	Drosophila	860:869	arg1	CG11388					838:844	CG11388	838:844	CG11388	838:844	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	5	56	theme	Drosophila	860:869	arg1	homolog					871:877	the Drosophila homolog	856:877	the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1)	856:925	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	10	57	contain	has	1698:1700	arg1	xylose					1691:1696	the second xylose	1680:1696	the second xylose	1680:1696	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	10	57	contain	has	1698:1700	arg2	role					1716:1719	a fine-tuning role	1702:1719	a fine-tuning role only revealed in sensitized genetic backgrounds	1702:1767	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	4	58	theme	second	672:677	arg1	xylose					679:684	the second xylose	668:684	the second xylose	668:684	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	1	59	theme	Notch	230:234	arg1	pathway					236:242	the Notch pathway	226:242	the Notch pathway	226:242	In multicellular organisms, glycosylation regulates various developmental signaling pathways including the Notch pathway.
30169771	9	60	theme	fly	1481:1483	arg1	shams					1491:1495	the fly Gxylt shams	1477:1495	the fly Gxylt shams	1477:1495	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	8	61	theme	interaction	1212:1222	arg1	experiments					1224:1234	genetic interaction experiments	1204:1234	genetic interaction experiments	1204:1234	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	6	62	theme	human	978:982	arg1	XXYLT1					984:989	human XXYLT1	978:989	human XXYLT1	978:989	Experiments in S2 cells indicated that similar to human XXYLT1, CG11388 can add the second xylose to xylose-glucose-O glycans.
30169771	2	63	theme	O-linked	256:263	arg1	glycans					265:271	the O-linked glycans	252:271	the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	252:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	9	64	theme	shams	1491:1495	arg1	copy					1469:1472	one copy	1465:1472	one copy of the fly Gxylt shams	1465:1495	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	8	65	theme	Notch	1308:1312	arg1	components					1322:1331	decreased or increased Notch pathway components	1285:1331	decreased or increased Notch pathway components	1285:1331	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	2	66	theme	factor-like	299:309	arg1	repeats					317:323	epidermal growth factor-like (EGF) repeats	282:323	epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	282:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	9	67	theme	Delta-mediated	1506:1519	arg1	activation					1527:1536	Delta-mediated Notch activation	1506:1536	Delta-mediated Notch activation	1506:1536	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	2	68	theme	epidermal	282:290	arg1	repeats					317:323	epidermal growth factor-like (EGF) repeats	282:323	epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors	282:372	One of the O-linked glycans added to epidermal growth factor-like (EGF) repeats in animal proteins including the Notch receptors is the xylose-xylose-glucose-O oligosaccharide.
30169771	4	69	theme	xylose	679:684	arg1	loss					642:645	the loss	638:645	the loss of the first xylose, the second xylose or both	638:692	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	6	70	theme	xylose-glucose-O	1029:1044	arg1	glycans					1046:1052	xylose-glucose-O glycans	1029:1052	xylose-glucose-O glycans	1029:1052	Experiments in S2 cells indicated that similar to human XXYLT1, CG11388 can add the second xylose to xylose-glucose-O glycans.
30169771	0	71	theme	Drosophila	95:104	arg1	signaling					112:120	Drosophila Notch signaling	95:120	Drosophila Notch signaling	95:120	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	1	72	theme	developmental	183:195	arg1	pathways					207:214	various developmental signaling pathways	175:214	various developmental signaling pathways	175:214	In multicellular organisms, glycosylation regulates various developmental signaling pathways including the Notch pathway.
30169771	8	73	theme	Xxylt	1342:1346	arg1	loss					1334:1337	loss	1334:1337	loss of Xxylt	1334:1346	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	5	74	theme	Notch	767:771	arg1	signaling					773:781	Drosophila Notch signaling	756:781	Drosophila Notch signaling	756:781	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	8	75	theme	Delta-mediated	1357:1370	arg1	activation					1372:1381	Delta-mediated activation	1357:1381	Delta-mediated activation of Notch	1357:1390	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	0	76	from	roles	51:55	arg1	signaling					112:120	Drosophila Notch signaling	95:120	Drosophila Notch signaling	95:120	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	0	77	theme	genetic	11:17	arg1	backgrounds					19:29	Sensitized genetic backgrounds	0:29	Sensitized genetic backgrounds	0:29	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	3	78	theme	Notch	497:501	arg1	signaling					503:511	Notch signaling	497:511	Notch signaling in specific contexts	497:532	Drosophila glucoside xylosyltransferase (Gxylt) Shams negatively regulates Notch signaling in specific contexts.
30169771	3	79	theme	glucoside	433:441	arg1	Shams					470:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams	422:474	Drosophila glucoside xylosyltransferase (Gxylt) Shams negatively regulates Notch signaling in specific contexts.
30169771	5	80	theme	genetic	818:824	arg1	analysis					826:833	biochemical and genetic analysis	802:833	biochemical and genetic analysis	802:833	To examine the contribution of the second xylose residues to Drosophila Notch signaling, we have performed biochemical and genetic analysis on CG11388, which is the Drosophila homolog of human xyloside xylosyltransferase 1 (XXYLT1).
30169771	8	81	theme	increased	1298:1306	arg1	components					1322:1331	decreased or increased Notch pathway components	1285:1331	decreased or increased Notch pathway components	1285:1331	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	0	82	theme	EGF	61:63	arg1	xylosyltransferases					72:90	EGF repeat xylosyltransferases	61:90	EGF repeat xylosyltransferases	61:90	Sensitized genetic backgrounds reveal differential roles for EGF repeat xylosyltransferases in Drosophila Notch signaling.
30169771	4	83	theme	first	556:560	arg1	residue					569:575	the first xylose residue	552:575	the first xylose residue to O-glucose	552:588	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	7	84	theme	CG11388	1084:1090	arg1	copies					1074:1079	both copies	1069:1079	both copies of CG11388 (Xxylt)	1069:1098	Flies lacking both copies of CG11388 (Xxylt) are viable and fertile and do not show gross phenotypes indicative of altered Notch signaling.
30169771	10	85	from	signaling	1655:1663	arg1	Drosophila					1668:1677	Drosophila	1668:1677	Drosophila	1668:1677	Taken together, these data indicate that while the first xylose plays a key role in tuning the Delta-mediated Notch signaling in Drosophila, the second xylose has a fine-tuning role only revealed in sensitized genetic backgrounds.
30169771	4	86	theme	xylose	660:665	arg1	loss					642:645	the loss	638:645	the loss of the first xylose, the second xylose or both	638:692	Since Shams adds the first xylose residue to O-glucose, its loss-of-function phenotype could be due to the loss of the first xylose, the second xylose or both.
30169771	9	87	theme	Gxylt	1485:1489	arg1	shams					1491:1495	the fly Gxylt shams	1477:1495	the fly Gxylt shams	1477:1495	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
30169771	8	88	with	backgrounds	1268:1278	arg1	components					1322:1331	decreased or increased Notch pathway components	1285:1331	decreased or increased Notch pathway components	1285:1331	However, genetic interaction experiments show that in sensitized genetic backgrounds with decreased or increased Notch pathway components, loss of Xxylt promotes Delta-mediated activation of Notch.
30169771	3	89	from	signaling	503:511	arg1	contexts					525:532	specific contexts	516:532	specific contexts	516:532	Drosophila glucoside xylosyltransferase (Gxylt) Shams negatively regulates Notch signaling in specific contexts.
30169771	7	90	theme	Notch	1178:1182	arg1	signaling					1184:1192	altered Notch signaling	1170:1192	altered Notch signaling	1170:1192	Flies lacking both copies of CG11388 (Xxylt) are viable and fertile and do not show gross phenotypes indicative of altered Notch signaling.
30169771	9	91	theme	such	1423:1426	arg1	backgrounds					1439:1449	such sensitized backgrounds	1423:1449	such sensitized backgrounds	1423:1449	Unexpectedly, we find that in such sensitized backgrounds, even loss of one copy of the fly Gxylt shams enhances Delta-mediated Notch activation.
29681862	7	0	theme	molecular	1368:1376	arg1	mechanisms					1378:1387	molecular mechanisms	1368:1387	molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction	1368:1437	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	3	1	theme	proteins	563:570	arg1	process					620:626	a unique posttranslational process	593:626	a unique posttranslational process that integrates glucose metabolism with intracellular protein activity	593:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	1	theme	proteins	563:570	arg1	modification					547:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	2	link	O-linked	505:512	arg1	process					620:626	a unique posttranslational process	593:626	a unique posttranslational process that integrates glucose metabolism with intracellular protein activity	593:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	2	link	O-linked	505:512	arg1	modification					547:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	10	3	theme	High	1918:1921	arg1	diet					1929:1932	High sugar diet	1918:1932	High sugar diet	1918:1932	High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT.
29681862	12	4	theme	vascular	2376:2383	arg1	dysfunction					2385:2395	vascular dysfunction	2376:2395	vascular dysfunction in conditions associated with hyperglycemia	2376:2439	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	8	5	from	O-GlcNAcylated-proteins	1656:1678	arg1	PVAT					1687:1690	the PVAT	1683:1690	the PVAT	1683:1690	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	3	6	theme	unique	595:600	arg1	process					620:626	a unique posttranslational process	593:626	a unique posttranslational process that integrates glucose metabolism with intracellular protein activity	593:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	6	theme	unique	595:600	arg1	modification					547:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	4	7	theme	hexosamine	738:747	arg1	pathway					762:768	the hexosamine biosynthetic pathway	734:768	the hexosamine biosynthetic pathway	734:768	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	2	8	theme	experimental	302:313	arg1	obesity					325:331	experimental and human obesity	302:331	experimental and human obesity	302:331	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	1	9	theme	adipose	210:216	arg1	tissue					218:223	the perivascular adipose tissue	193:223	the perivascular adipose tissue (PVAT)	193:230	Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility.
29681862	1	9	theme	adipose	210:216	arg1	PVAT					226:229	PVAT	226:229	PVAT	226:229	Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility.
29681862	9	10	theme	NO	1802:1803	arg1	formation					1805:1813	decreased NO formation	1792:1813	decreased NO formation	1792:1813	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	2	11	from	changes	380:386	arg1	function					396:403	PVAT function	391:403	PVAT function	391:403	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	7	12	theme	sugar	1535:1539	arg1	diet					1541:1544	either a control or high sugar diet	1510:1544	diet	1541:1544	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	4	13	attach	linked	861:866	arg2	flux					710:713	Increased flux	700:713	Increased flux of glucose through the hexosamine biosynthetic pathway	700:768	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	13	attach	linked	861:866	arg2	increase					789:796	the consequent increase	774:796	the consequent increase in tissue-specific O-GlcNAc modification of proteins	774:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	13	attach	linked	861:866	arg1	facets					880:885	multiple facets	871:885	multiple facets of vascular dysfunction in diabetes and other pathological conditions	871:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	0	14	theme	Metabolic	141:149	arg1	Syndrome					151:158	Metabolic Syndrome	141:158	Metabolic Syndrome	141:158	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	12	15	gly	O-GlcNAcylation	2294:2308	arg1	development					2341:2351	the development	2337:2351	the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia	2337:2439	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	0	16	from	Properties	96:105	arg1	Syndrome					151:158	Metabolic Syndrome	141:158	Metabolic Syndrome	141:158	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	3	17	theme	intracellular	668:680	arg1	activity					690:697	intracellular protein activity	668:697	intracellular protein activity	668:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	9	18	theme	endothelial	1838:1848	arg1	eNOS					1873:1876	eNOS	1873:1876	eNOS	1873:1876	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	9	18	theme	endothelial	1838:1848	arg1	synthase					1863:1870	endothelial nitric oxide synthase	1838:1870	endothelial nitric oxide synthase (eNOS)	1838:1877	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	4	19	theme	tissue-specific	801:815	arg1	modification					826:837	tissue-specific O-GlcNAc modification	801:837	tissue-specific O-GlcNAc modification of proteins	801:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	11	20	theme	increased	2084:2092	arg1	levels					2094:2099	increased levels	2084:2099	increased levels of O-GlcNAc-modified proteins	2084:2129	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	9	21	theme	oxide	1857:1861	arg1	eNOS					1873:1876	eNOS	1873:1876	eNOS	1873:1876	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	9	21	theme	oxide	1857:1861	arg1	synthase					1863:1870	endothelial nitric oxide synthase	1838:1870	endothelial nitric oxide synthase (eNOS)	1838:1877	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	6	22	theme	vasorelaxant	1335:1346	arg1	function					1348:1355	PVAT vasorelaxant function	1330:1355	PVAT vasorelaxant function	1330:1355	Therefore, the current study was devised to determine whether a high-sugar diet increases O-GlcNAcylation in the PVAT and how increased O-GlcNAc interferes with PVAT vasorelaxant function.
29681862	7	23	theme	Wistar	1494:1499	arg1	rats					1501:1504	Wistar rats	1494:1504	Wistar rats fed either a control or high sugar diet	1494:1544	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	11	24	from	patients	2068:2075	arg1	samples					2041:2047	Visceral adipose tissue samples	2017:2047	Visceral adipose tissue samples from hyperglycemic patients	2017:2075	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	12	25	theme	syndrome-induced	2251:2266	arg1	dysfunction					2273:2283	metabolic syndrome-induced PVAT dysfunction	2241:2283	metabolic syndrome-induced PVAT dysfunction	2241:2283	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	10	26	theme	OGA	1949:1951	arg1	activity					1953:1960	OGA activity	1949:1960	OGA activity	1949:1960	High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT.
29681862	5	27	theme	metabolic	1042:1050	arg1	syndrome					1052:1059	metabolic syndrome	1042:1059	metabolic syndrome	1042:1059	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	3	28	theme	O-linked	505:512	arg1	process					620:626	a unique posttranslational process	593:626	a unique posttranslational process that integrates glucose metabolism with intracellular protein activity	593:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	28	theme	O-linked	505:512	arg1	modification					547:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	11	29	theme	proteins	2122:2129	arg1	levels					2094:2099	increased levels	2084:2099	increased levels of O-GlcNAc-modified proteins	2084:2129	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	11	29	theme	proteins	2122:2129	arg1	activity					2175:2182	decreased OGA activity	2161:2182	decreased OGA activity	2161:2182	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	11	29	theme	proteins	2122:2129	arg1	generation					2146:2155	increased ROS generation	2132:2155	increased ROS generation	2132:2155	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	8	30	theme	sugar	1596:1600	arg1	diet					1602:1605	a high sugar diet	1589:1605	a high sugar diet	1589:1605	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	4	31	from	facets	880:885	arg1	conditions					946:955	other pathological conditions	927:955	other pathological conditions	927:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	31	from	facets	880:885	arg1	diabetes					914:921	diabetes	914:921	diabetes	914:921	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	9	32	theme	increased	1883:1891	arg1	O-GlcNAcylation					1893:1907	increased O-GlcNAcylation	1883:1907	increased O-GlcNAcylation of eNOS	1883:1915	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	11	33	theme	increased	2132:2140	arg1	generation					2146:2155	increased ROS generation	2132:2155	increased ROS generation	2132:2155	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	0	34	theme	Perivascular	110:121	arg1	Tissue					131:136	Perivascular Adipose Tissue	110:136	Perivascular Adipose Tissue	110:136	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	2	35	theme	human	319:323	arg1	obesity					325:331	experimental and human obesity	302:331	experimental and human obesity	302:331	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	5	36	theme	O-GlcNAc	1081:1088	arg1	modification					1090:1101	increased O-GlcNAc modification	1071:1101	increased O-GlcNAc modification of proteins in the PVAT	1071:1125	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	12	37	theme	metabolic	2241:2249	arg1	dysfunction					2273:2283	metabolic syndrome-induced PVAT dysfunction	2241:2283	metabolic syndrome-induced PVAT dysfunction	2241:2283	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	8	38	theme	syndrome	1627:1634	arg1	features					1636:1643	metabolic syndrome features	1617:1643	metabolic syndrome features	1617:1643	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	2	39	theme	vascular	423:430	arg1	dysfunction					432:442	vascular dysfunction	423:442	vascular dysfunction associated with increased body weight and hyperglycemia	423:498	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	0	40	theme	Tissue	131:136	arg1	Properties					96:105	the Anti-contractile Properties	75:105	the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome	75:158	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	4	41	theme	proteins	842:849	arg1	modification					826:837	tissue-specific O-GlcNAc modification	801:837	tissue-specific O-GlcNAc modification of proteins	801:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	0	42	theme	Increased	0:8	arg1	O-GlcNAcylation					10:24	Increased O-GlcNAcylation	0:24	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase	0:61	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	11	43	theme	decreased	2161:2169	arg1	activity					2175:2182	decreased OGA activity	2161:2182	decreased OGA activity	2161:2182	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	11	44	theme	O-GlcNAc-modified	2104:2120	arg1	proteins					2122:2129	O-GlcNAc-modified proteins	2104:2129	O-GlcNAc-modified proteins	2104:2129	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	2	45	theme	increased	460:468	arg1	weight					475:480	increased body weight	460:480	increased body weight	460:480	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	1	46	theme	physiological	167:179	arg1	conditions					181:190	physiological conditions	167:190	physiological conditions	167:190	Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility.
29681862	10	47	theme	superoxide	1976:1985	arg1	generation					1993:2002	increased superoxide anion generation	1966:2002	increased superoxide anion generation	1966:2002	High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT.
29681862	0	48	theme	Nitric	41:46	arg1	Synthase					54:61	Endothelial Nitric Oxide Synthase	29:61	Endothelial Nitric Oxide Synthase	29:61	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	4	49	theme	pathological	933:944	arg1	conditions					946:955	other pathological conditions	927:955	other pathological conditions	927:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	0	50	theme	Synthase	54:61	arg1	O-GlcNAcylation					10:24	Increased O-GlcNAcylation	0:24	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase	0:61	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	5	51	theme	anti-contractile	1143:1158	arg1	effects					1160:1166	its anti-contractile effects	1139:1166	its anti-contractile effects	1139:1166	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	7	52	theme	PVAT	1422:1425	arg1	dysfunction					1427:1437	PVAT dysfunction	1422:1437	PVAT dysfunction	1422:1437	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	4	53	theme	vascular	890:897	arg1	dysfunction					899:909	vascular dysfunction	890:909	vascular dysfunction in diabetes and other pathological conditions	890:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	1	54	theme	vascular	253:260	arg1	contractility					262:274	vascular contractility	253:274	vascular contractility	253:274	Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility.
29681862	9	55	theme	high	1744:1747	arg1	rats					1764:1767	high sugar diet-fed rats	1744:1767	high sugar diet-fed rats	1744:1767	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	8	56	theme	anti-contractile	1709:1724	arg1	effect					1726:1731	PVAT anti-contractile effect	1704:1731	PVAT anti-contractile effect	1704:1731	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	5	57	theme	chronic	979:985	arg1	consumption					987:997	chronic consumption	979:997	chronic consumption of glucose, a condition that progresses to metabolic syndrome,	979:1060	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	9	58	dep	exhibited	1782:1790	arg1	reduced					1816:1822	reduced	1816:1822	reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS	1816:1915	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	9	59	theme	diet-fed	1755:1762	arg1	rats					1764:1767	high sugar diet-fed rats	1744:1767	high sugar diet-fed rats	1744:1767	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	4	60	mod	modification	826:837	arg1	proteins					842:849	proteins	842:849	proteins	842:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	60	mod	modification	826:837	arg3	O-GlcNAc					817:824	tissue-specific O-GlcNAc modification	801:837	tissue-specific O-GlcNAc modification of proteins	801:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	12	61	theme	therapies	2362:2370	arg1	development					2341:2351	the development	2337:2351	the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia	2337:2439	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	5	62	mod	modification	1090:1101	arg1	proteins					1106:1113	proteins	1106:1113	proteins	1106:1113	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	5	62	mod	modification	1090:1101	arg3	O-GlcNAc					1081:1088	increased O-GlcNAc modification	1071:1101	increased O-GlcNAc modification of proteins in the PVAT	1071:1125	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	11	63	theme	ROS	2142:2144	arg1	generation					2146:2155	increased ROS generation	2132:2155	increased ROS generation	2132:2155	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	1	64	theme	perivascular	197:208	arg1	tissue					218:223	the perivascular adipose tissue	193:223	the perivascular adipose tissue (PVAT)	193:230	Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility.
29681862	1	64	theme	perivascular	197:208	arg1	PVAT					226:229	PVAT	226:229	PVAT	226:229	Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility.
29681862	9	65	theme	decreased	1792:1800	arg1	formation					1805:1813	decreased NO formation	1792:1813	decreased NO formation	1792:1813	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	9	66	from	rats	1764:1767	arg1	PVAT					1734:1737	PVAT	1734:1737	PVAT from high sugar diet-fed rats for 12 weeks	1734:1780	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	8	67	from	loss	1696:1699	arg1	PVAT					1687:1690	the PVAT	1683:1690	the PVAT	1683:1690	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	2	68	theme	metabolic	344:352	arg1	syndrome					354:361	the metabolic syndrome	340:361	the metabolic syndrome	340:361	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	4	69	theme	biosynthetic	749:760	arg1	pathway					762:768	the hexosamine biosynthetic pathway	734:768	the hexosamine biosynthetic pathway	734:768	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	12	70	theme	novel	2356:2360	arg1	therapies					2362:2370	novel therapies	2356:2370	novel therapies for vascular dysfunction in conditions associated with hyperglycemia	2356:2439	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	3	71	theme	posttranslational	602:618	arg1	process					620:626	a unique posttranslational process	593:626	a unique posttranslational process that integrates glucose metabolism with intracellular protein activity	593:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	71	theme	posttranslational	602:618	arg1	modification					547:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	12	72	from	dysfunction	2385:2395	arg1	conditions					2400:2409	conditions	2400:2409	conditions associated with hyperglycemia	2400:2439	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	11	73	theme	hyperglycemic	2054:2066	arg1	patients					2068:2075	hyperglycemic patients	2054:2075	hyperglycemic patients	2054:2075	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	7	74	theme	high	1530:1533	arg1	diet					1541:1544	either a control or high sugar diet	1510:1544	diet	1541:1544	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	12	75	theme	PVAT	2268:2271	arg1	dysfunction					2273:2283	metabolic syndrome-induced PVAT dysfunction	2241:2283	metabolic syndrome-induced PVAT dysfunction	2241:2283	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	4	76	from	flux	710:713	arg1	modification					826:837	tissue-specific O-GlcNAc modification	801:837	tissue-specific O-GlcNAc modification of proteins	801:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	3	77	mod	modification	547:558	arg1	proteins					563:570	proteins	563:570	proteins (O-GlcNAcylation)	563:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	77	mod	modification	547:558	arg3	O-GlcNAc					537:544	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	77	mod	modification	547:558	arg1	O-GlcNAcylation					573:587	O-GlcNAcylation	573:587	O-GlcNAcylation	573:587	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	77	mod	modification	547:558	arg3	β-N-acetylglucosamine					514:534	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	4	78	theme	glucose	718:724	arg1	flux					710:713	Increased flux	700:713	Increased flux of glucose through the hexosamine biosynthetic pathway	700:768	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	78	theme	glucose	718:724	arg1	increase					789:796	the consequent increase	774:796	the consequent increase in tissue-specific O-GlcNAc modification of proteins	774:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	3	79	theme	glucose	644:650	arg1	metabolism					652:661	glucose metabolism	644:661	glucose metabolism	644:661	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	6	80	theme	increased	1295:1303	arg1	O-GlcNAc					1305:1312	increased O-GlcNAc	1295:1312	increased O-GlcNAc	1295:1312	Therefore, the current study was devised to determine whether a high-sugar diet increases O-GlcNAcylation in the PVAT and how increased O-GlcNAc interferes with PVAT vasorelaxant function.
29681862	9	81	theme	nitric	1850:1855	arg1	eNOS					1873:1876	eNOS	1873:1876	eNOS	1873:1876	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	9	81	theme	nitric	1850:1855	arg1	synthase					1863:1870	endothelial nitric oxide synthase	1838:1870	endothelial nitric oxide synthase (eNOS)	1838:1877	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	4	82	from	diabetes	914:921	arg1	facets					880:885	multiple facets	871:885	multiple facets of vascular dysfunction in diabetes and other pathological conditions	871:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	11	83	theme	OGA	2171:2173	arg1	activity					2175:2182	decreased OGA activity	2161:2182	decreased OGA activity	2161:2182	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	9	84	theme	synthase	1863:1870	arg1	expression					1824:1833	expression	1824:1833	expression of endothelial nitric oxide synthase (eNOS)	1824:1877	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	9	84	theme	synthase	1863:1870	arg1	O-GlcNAcylation					1893:1907	increased O-GlcNAcylation	1883:1907	increased O-GlcNAcylation of eNOS	1883:1915	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	8	85	theme	high	1591:1594	arg1	diet					1602:1605	a high sugar diet	1589:1605	a high sugar diet	1589:1605	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	6	86	theme	PVAT	1330:1333	arg1	function					1348:1355	PVAT vasorelaxant function	1330:1355	PVAT vasorelaxant function	1330:1355	Therefore, the current study was devised to determine whether a high-sugar diet increases O-GlcNAcylation in the PVAT and how increased O-GlcNAc interferes with PVAT vasorelaxant function.
29681862	4	87	theme	O-GlcNAc	817:824	arg1	modification					826:837	tissue-specific O-GlcNAc modification	801:837	tissue-specific O-GlcNAc modification of proteins	801:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	0	88	theme	Anti-contractile	79:94	arg1	Properties					96:105	the Anti-contractile Properties	75:105	the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome	75:158	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	3	89	theme	protein	682:688	arg1	activity					690:697	intracellular protein activity	668:697	intracellular protein activity	668:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	4	90	from	dysfunction	899:909	arg1	conditions					946:955	other pathological conditions	927:955	other pathological conditions	927:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	90	from	dysfunction	899:909	arg1	diabetes					914:921	diabetes	914:921	diabetes	914:921	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	5	91	theme	glucose	1002:1008	arg1	consumption					987:997	chronic consumption	979:997	chronic consumption of glucose, a condition that progresses to metabolic syndrome,	979:1060	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	7	92	attach	isolated	1480:1487	arg1	rats					1501:1504	Wistar rats	1494:1504	Wistar rats fed either a control or high sugar diet	1494:1544	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	7	92	attach	isolated	1480:1487	arg2	aortas					1449:1454	thoracic aortas	1440:1454	thoracic aortas surrounded by PVAT	1440:1473	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	8	93	theme	metabolic	1617:1625	arg1	features					1636:1643	metabolic syndrome features	1617:1643	metabolic syndrome features	1617:1643	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	4	94	theme	consequent	778:787	arg1	increase					789:796	the consequent increase	774:796	the consequent increase in tissue-specific O-GlcNAc modification of proteins	774:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	0	95	theme	Adipose	123:129	arg1	Tissue					131:136	Perivascular Adipose Tissue	110:136	Perivascular Adipose Tissue	110:136	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	5	96	theme	increased	1071:1079	arg1	modification					1090:1101	increased O-GlcNAc modification	1071:1101	increased O-GlcNAc modification of proteins in the PVAT	1071:1125	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	9	97	theme	eNOS	1912:1915	arg1	expression					1824:1833	expression	1824:1833	expression of endothelial nitric oxide synthase (eNOS)	1824:1877	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	9	97	theme	eNOS	1912:1915	arg1	O-GlcNAcylation					1893:1907	increased O-GlcNAcylation	1883:1907	increased O-GlcNAcylation of eNOS	1883:1915	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	8	98	theme	increased	1646:1654	arg1	O-GlcNAcylated-proteins					1656:1678	increased O-GlcNAcylated-proteins	1646:1678	increased O-GlcNAcylated-proteins in the PVAT	1646:1690	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	4	99	theme	multiple	871:878	arg1	facets					880:885	multiple facets	871:885	multiple facets of vascular dysfunction in diabetes and other pathological conditions	871:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	11	100	theme	tissue	2034:2039	arg1	samples					2041:2047	Visceral adipose tissue samples	2017:2047	Visceral adipose tissue samples from hyperglycemic patients	2017:2075	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	4	101	from	conditions	946:955	arg1	facets					880:885	multiple facets	871:885	multiple facets of vascular dysfunction in diabetes and other pathological conditions	871:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	6	102	theme	current	1184:1190	arg1	study					1192:1196	the current study	1180:1196	the current study	1180:1196	Therefore, the current study was devised to determine whether a high-sugar diet increases O-GlcNAcylation in the PVAT and how increased O-GlcNAc interferes with PVAT vasorelaxant function.
29681862	11	103	theme	Visceral	2017:2024	arg1	samples					2041:2047	Visceral adipose tissue samples	2017:2047	Visceral adipose tissue samples from hyperglycemic patients	2017:2075	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	0	104	theme	Endothelial	29:39	arg1	Synthase					54:61	Endothelial Nitric Oxide Synthase	29:61	Endothelial Nitric Oxide Synthase	29:61	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	7	105	theme	thoracic	1440:1447	arg1	aortas					1449:1454	thoracic aortas	1440:1454	thoracic aortas surrounded by PVAT	1440:1473	To assess molecular mechanisms by which O-GlcNAc contributes to PVAT dysfunction, thoracic aortas surrounded by PVAT were isolated from Wistar rats fed either a control or high sugar diet, for 10 and 12 weeks.
29681862	2	106	theme	body	470:473	arg1	weight					475:480	increased body weight	460:480	increased body weight	460:480	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	12	107	theme	eNOS	2313:2316	arg1	O-GlcNAcylation					2294:2308	O-GlcNAcylation	2294:2308	O-GlcNAcylation of eNOS	2294:2316	These data indicate that O-GlcNAcylation contributes to metabolic syndrome-induced PVAT dysfunction and that O-GlcNAcylation of eNOS may be targeted in the development of novel therapies for vascular dysfunction in conditions associated with hyperglycemia.
29681862	10	108	theme	anion	1987:1991	arg1	generation					1993:2002	increased superoxide anion generation	1966:2002	increased superoxide anion generation	1966:2002	High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT.
29681862	3	109	theme	β-N-acetylglucosamine	514:534	arg1	process					620:626	a unique posttranslational process	593:626	a unique posttranslational process that integrates glucose metabolism with intracellular protein activity	593:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	109	theme	β-N-acetylglucosamine	514:534	arg1	modification					547:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	0	110	theme	Oxide	48:52	arg1	Synthase					54:61	Endothelial Nitric Oxide Synthase	29:61	Endothelial Nitric Oxide Synthase	29:61	Increased O-GlcNAcylation of Endothelial Nitric Oxide Synthase Compromises the Anti-contractile Properties of Perivascular Adipose Tissue in Metabolic Syndrome.
29681862	11	111	theme	adipose	2026:2032	arg1	samples					2041:2047	Visceral adipose tissue samples	2017:2047	Visceral adipose tissue samples from hyperglycemic patients	2017:2075	Visceral adipose tissue samples from hyperglycemic patients showed increased levels of O-GlcNAc-modified proteins, increased ROS generation and decreased OGA activity.
29681862	10	112	theme	increased	1966:1974	arg1	generation					1993:2002	increased superoxide anion generation	1966:2002	increased superoxide anion generation	1966:2002	High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT.
29681862	8	113	from	features	1636:1643	arg1	PVAT					1687:1690	the PVAT	1683:1690	the PVAT	1683:1690	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	8	114	theme	PVAT	1704:1707	arg1	effect					1726:1731	PVAT anti-contractile effect	1704:1731	PVAT anti-contractile effect	1704:1731	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	4	115	theme	other	927:931	arg1	conditions					946:955	other pathological conditions	927:955	other pathological conditions	927:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	5	116	theme	proteins	1106:1113	arg1	modification					1090:1101	increased O-GlcNAc modification	1071:1101	increased O-GlcNAc modification of proteins in the PVAT	1071:1125	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29681862	10	117	theme	sugar	1923:1927	arg1	diet					1929:1932	High sugar diet	1918:1932	High sugar diet	1918:1932	High sugar diet also decreased OGA activity and increased superoxide anion generation in the PVAT.
29681862	6	118	theme	high-sugar	1233:1242	arg1	diet					1244:1247	a high-sugar diet	1231:1247	a high-sugar diet	1231:1247	Therefore, the current study was devised to determine whether a high-sugar diet increases O-GlcNAcylation in the PVAT and how increased O-GlcNAc interferes with PVAT vasorelaxant function.
29681862	8	119	theme	effect	1726:1731	arg1	features					1636:1643	metabolic syndrome features	1617:1643	metabolic syndrome features	1617:1643	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	8	119	theme	effect	1726:1731	arg1	O-GlcNAcylated-proteins					1656:1678	increased O-GlcNAcylated-proteins	1646:1678	increased O-GlcNAcylated-proteins in the PVAT	1646:1690	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	8	119	theme	effect	1726:1731	arg1	loss					1696:1699	loss	1696:1699	loss of PVAT anti-contractile effect	1696:1731	Rats chronically fed a high sugar diet exhibited metabolic syndrome features, increased O-GlcNAcylated-proteins in the PVAT and loss of PVAT anti-contractile effect.
29681862	3	120	theme	O-GlcNAc	537:544	arg1	process					620:626	a unique posttranslational process	593:626	a unique posttranslational process that integrates glucose metabolism with intracellular protein activity	593:697	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	3	120	theme	O-GlcNAc	537:544	arg1	modification					547:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	501:558	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation)	501:588	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity.
29681862	9	121	theme	sugar	1749:1753	arg1	rats					1764:1767	high sugar diet-fed rats	1744:1767	high sugar diet-fed rats	1744:1767	PVAT from high sugar diet-fed rats for 12 weeks exhibited decreased NO formation, reduced expression of endothelial nitric oxide synthase (eNOS) and increased O-GlcNAcylation of eNOS.
29681862	4	122	from	increase	789:796	arg1	modification					826:837	tissue-specific O-GlcNAc modification	801:837	tissue-specific O-GlcNAc modification of proteins	801:849	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	123	theme	Increased	700:708	arg1	flux					710:713	Increased flux	700:713	Increased flux of glucose through the hexosamine biosynthetic pathway	700:768	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	4	124	theme	dysfunction	899:909	arg1	facets					880:885	multiple facets	871:885	multiple facets of vascular dysfunction in diabetes and other pathological conditions	871:955	Increased flux of glucose through the hexosamine biosynthetic pathway and the consequent increase in tissue-specific O-GlcNAc modification of proteins have been linked to multiple facets of vascular dysfunction in diabetes and other pathological conditions.
29681862	2	125	theme	PVAT	391:394	arg1	function					396:403	PVAT function	391:403	PVAT function	391:403	This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia.
29681862	5	126	from	modification	1090:1101	arg1	PVAT					1122:1125	the PVAT	1118:1125	the PVAT	1118:1125	We hypothesized that chronic consumption of glucose, a condition that progresses to metabolic syndrome, leads to increased O-GlcNAc modification of proteins in the PVAT, decreasing its anti-contractile effects.
29382892	0	0	theme	Infrared	88:95	arg1	Spectroscopy					97:108	Infrared Spectroscopy	88:108	Infrared Spectroscopy	88:108	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	5	1	theme	cell	838:841	arg1	Fourier					843:849	Whole cell Fourier	832:849	Whole cell Fourier transform infrared (FTIR) spectroscopy	832:888	Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus.
29382892	4	2	theme	convenient	768:777	arg1	methods					779:785	rapid, reliable, and convenient methods	747:785	rapid, reliable, and convenient methods	747:785	However, there is a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues.
29382892	1	3	theme	carbohydrate	177:188	arg1	moieties					190:197	Surface carbohydrate moieties	169:197	Surface carbohydrate moieties	169:197	Surface carbohydrate moieties are essential for bacterial communication, phage-bacteria and host-pathogen interaction.
29382892	6	4	theme	WTA	1042:1044	arg1	expression					1046:1055	WTA expression	1042:1055	WTA expression	1042:1055	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	2	5	link	β-O-linked	403:412	arg1	residues					451:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	7	6	theme	α-	1199:1200	arg1	substituents					1220:1231	α- or β-O-GlcNAc WTA substituents	1199:1231	α- or β-O-GlcNAc WTA substituents	1199:1231	We could demonstrate that α- or β-O-GlcNAc WTA substituents can be clearly differentiated by chemometrically assisted FTIR spectroscopy.
29382892	2	7	theme	N-acetyl-glucosamine	414:433	arg1	residues					451:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	7	8	theme	assisted	1282:1289	arg1	spectroscopy					1296:1307	chemometrically assisted FTIR spectroscopy	1266:1307	chemometrically assisted FTIR spectroscopy	1266:1307	We could demonstrate that α- or β-O-GlcNAc WTA substituents can be clearly differentiated by chemometrically assisted FTIR spectroscopy.
29382892	8	9	theme	options	1493:1499	arg1	range					1484:1488	a complete new range	1469:1488	a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode	1469:1565	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	3	10	theme	beta-lactam	629:639	arg1	resistance					641:650	beta-lactam resistance	629:650	beta-lactam resistance	629:650	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	7	11	theme	FTIR	1291:1294	arg1	spectroscopy					1296:1307	chemometrically assisted FTIR spectroscopy	1266:1307	chemometrically assisted FTIR spectroscopy	1266:1307	We could demonstrate that α- or β-O-GlcNAc WTA substituents can be clearly differentiated by chemometrically assisted FTIR spectroscopy.
29382892	8	12	theme	glycosylation	1438:1450	arg1	analysis					1422:1429	large scale analysis	1410:1429	large scale analysis of WTA glycosylation	1410:1450	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	7	13	theme	WTA	1216:1218	arg1	substituents					1220:1231	α- or β-O-GlcNAc WTA substituents	1199:1231	α- or β-O-GlcNAc WTA substituents	1199:1231	We could demonstrate that α- or β-O-GlcNAc WTA substituents can be clearly differentiated by chemometrically assisted FTIR spectroscopy.
29382892	2	14	theme	teichoic	354:361	arg1	WTAs					370:373	WTAs	370:373	WTAs	370:373	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	2	14	theme	teichoic	354:361	arg1	acids					363:367	polyribitolphosphate type Wall teichoic acids	323:367	polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	323:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	6	15	theme	complete	1025:1032	arg1	loss					1034:1037	a complete loss	1023:1037	a complete loss of WTA expression	1023:1055	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	3	16	theme	host	574:577	arg1	cells					579:583	host cells	574:583	host cells	574:583	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	8	17	theme	FTIR	1346:1349	arg1	spectroscopy					1351:1362	whole cell FTIR spectroscopy	1335:1362	whole cell FTIR spectroscopy	1335:1362	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	2	18	theme	Wall	349:352	arg1	WTAs					370:373	WTAs	370:373	WTAs	370:373	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	2	18	theme	Wall	349:352	arg1	acids					363:367	polyribitolphosphate type Wall teichoic acids	323:367	polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	323:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	5	19	theme	infrared	861:868	arg1	spectroscopy					877:888	infrared (FTIR) spectroscopy	861:888	infrared (FTIR) spectroscopy	861:888	Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus.
29382892	0	20	theme	novel	119:123	arg1	insights					125:132	novel insights	119:132	novel insights into the staphylococcal glycocode	119:166	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	8	21	theme	large	1410:1414	arg1	analysis					1422:1429	large scale analysis	1410:1429	large scale analysis of WTA glycosylation	1410:1450	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	3	22	theme	particular	497:506	arg1	interest					508:515	particular interest	497:515	particular interest	497:515	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	2	23	theme	type	344:347	arg1	WTAs					370:373	WTAs	370:373	WTAs	370:373	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	2	23	theme	type	344:347	arg1	acids					363:367	polyribitolphosphate type Wall teichoic acids	323:367	polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	323:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	6	24	theme	phosphorus-containing	1140:1160	arg1	molecules					1162:1170	phosphorus-containing molecules	1140:1170	phosphorus-containing molecules	1140:1170	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	3	25	theme	GlcNAc	461:466	arg1	modifications					468:480	GlcNAc modifications	461:480	GlcNAc modifications	461:480	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	3	26	theme	phage	597:601	arg1	susceptibility					603:616	phage susceptibility	597:616	phage susceptibility conferring beta-lactam resistance	597:650	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	8	27	theme	whole	1335:1339	arg1	spectroscopy					1351:1362	whole cell FTIR spectroscopy	1335:1362	whole cell FTIR spectroscopy	1335:1362	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	8	28	theme	cell	1341:1344	arg1	spectroscopy					1351:1362	whole cell FTIR spectroscopy	1335:1362	whole cell FTIR spectroscopy	1335:1362	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	6	29	theme	strong	1069:1074	arg1	perturbations					1090:1102	strong FTIR spectral perturbations	1069:1102	strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules	1069:1170	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	5	30	dep	infrared	861:868	arg1	FTIR					871:874	FTIR	871:874	FTIR	871:874	Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus.
29382892	3	31	theme	important	663:671	arg1	target					673:678	an important target	660:678	an important target for antimicrobial agents and vaccines	660:716	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	1	32	theme	bacterial	217:225	arg1	communication					227:239	bacterial communication	217:239	bacterial communication	217:239	Surface carbohydrate moieties are essential for bacterial communication, phage-bacteria and host-pathogen interaction.
29382892	0	33	theme	aureus	27:32	arg1	glycoepitopes					53:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	8	34	theme	reliable	1390:1397	arg1	method					1399:1404	a powerful and reliable method	1375:1404	a powerful and reliable method for large scale analysis of WTA glycosylation	1375:1450	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	0	35	dep	Fourier	70:76	arg1	Transform					78:86	Transform	78:86	Transform Infrared Spectroscopy	78:108	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	8	36	theme	new	1480:1482	arg1	range					1484:1488	a complete new range	1469:1488	a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode	1469:1565	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	5	37	dep	Fourier	843:849	arg1	transform					851:859	transform	851:859	transform infrared (FTIR) spectroscopy	851:888	Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus.
29382892	4	38	theme	sugar	816:820	arg1	residues					822:829	these sugar residues	810:829	these sugar residues	810:829	However, there is a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues.
29382892	3	39	theme	staphylococcal	547:560	arg1	adhesion					562:569	staphylococcal adhesion	547:569	staphylococcal adhesion to host cells	547:583	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	0	40	theme	teichoic	39:46	arg1	glycoepitopes					53:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	8	41	theme	powerful	1377:1384	arg1	method					1399:1404	a powerful and reliable method	1375:1404	a powerful and reliable method for large scale analysis of WTA glycosylation	1375:1450	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	6	42	dep	S.	990:991	arg1	aureus					993:998	aureus	993:998	aureus	993:998	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	3	43	theme	antimicrobial	684:696	arg1	agents					698:703	antimicrobial agents	684:703	antimicrobial agents	684:703	GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines.
29382892	4	44	theme	rapid	747:751	arg1	methods					779:785	rapid, reliable, and convenient methods	747:785	rapid, reliable, and convenient methods	747:785	However, there is a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues.
29382892	6	45	theme	spectral	1081:1088	arg1	perturbations					1090:1102	strong FTIR spectral perturbations	1069:1102	strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules	1069:1170	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	0	46	theme	wall	34:37	arg1	glycoepitopes					53:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	0	47	theme	staphylococcal	143:156	arg1	glycocode					158:166	the staphylococcal glycocode	139:166	the staphylococcal glycocode	139:166	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	8	48	theme	complete	1471:1478	arg1	range					1484:1488	a complete new range	1469:1488	a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode	1469:1565	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	6	49	theme	FTIR	1076:1079	arg1	perturbations					1090:1102	strong FTIR spectral perturbations	1069:1102	strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules	1069:1170	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	0	50	theme	glycoepitopes	53:65	arg1	Analysis					0:7	Analysis	0:7	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy	0:108	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	8	51	dep	related	1549:1555	arg1	glycocode					1557:1565	glycocode	1557:1565	glycocode	1557:1565	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	8	52	theme	WTA	1434:1436	arg1	glycosylation					1438:1450	WTA glycosylation	1434:1450	WTA glycosylation	1434:1450	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	8	53	theme	related	1549:1555	arg1	pathogenesis					1536:1547	the staphylococcal pathogenesis	1517:1547	the staphylococcal pathogenesis related glycocode	1517:1565	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	2	54	theme	β-O-linked	403:412	arg1	residues					451:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	0	55	theme	acid	48:51	arg1	glycoepitopes					53:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Staphylococcus aureus wall teichoic acid glycoepitopes	12:65	Analysis of Staphylococcus aureus wall teichoic acid glycoepitopes by Fourier Transform Infrared Spectroscopy provides novel insights into the staphylococcal glycocode.
29382892	8	56	theme	scale	1416:1420	arg1	analysis					1422:1429	large scale analysis	1410:1429	large scale analysis of WTA glycosylation	1410:1450	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	4	57	theme	methods	779:785	arg1	lack					739:742	a lack	737:742	a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues	737:829	However, there is a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues.
29382892	8	58	theme	staphylococcal	1521:1534	arg1	pathogenesis					1536:1547	the staphylococcal pathogenesis	1517:1547	the staphylococcal pathogenesis related glycocode	1517:1565	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	6	59	theme	S.	990:991	arg1	mutants					1000:1006	S. aureus mutants	990:1006	S. aureus mutants	990:1006	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	7	60	theme	β-O-GlcNAc	1205:1214	arg1	substituents					1220:1231	α- or β-O-GlcNAc WTA substituents	1199:1231	α- or β-O-GlcNAc WTA substituents	1199:1231	We could demonstrate that α- or β-O-GlcNAc WTA substituents can be clearly differentiated by chemometrically assisted FTIR spectroscopy.
29382892	2	61	theme	polyribitolphosphate	323:342	arg1	WTAs					370:373	WTAs	370:373	WTAs	370:373	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	2	61	theme	polyribitolphosphate	323:342	arg1	acids					363:367	polyribitolphosphate type Wall teichoic acids	323:367	polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	323:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	4	62	theme	reliable	754:761	arg1	methods					779:785	rapid, reliable, and convenient methods	747:785	rapid, reliable, and convenient methods	747:785	However, there is a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues.
29382892	2	63	theme	α-	393:394	arg1	residues					451:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	1	64	theme	host-pathogen	261:273	arg1	interaction					275:285	host-pathogen interaction	261:285	host-pathogen interaction	261:285	Surface carbohydrate moieties are essential for bacterial communication, phage-bacteria and host-pathogen interaction.
29382892	5	65	gly	glycosylation	956:968	arg1	aureus					976:981	S. aureus	973:981	S. aureus	973:981	Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus.
29382892	6	66	theme	related	1111:1117	arg1	perturbations					1090:1102	strong FTIR spectral perturbations	1069:1102	strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules	1069:1170	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
29382892	1	67	theme	Surface	169:175	arg1	moieties					190:197	Surface carbohydrate moieties	169:197	Surface carbohydrate moieties	169:197	Surface carbohydrate moieties are essential for bacterial communication, phage-bacteria and host-pathogen interaction.
29382892	5	68	theme	WTA	952:954	arg1	glycosylation					956:968	WTA glycosylation	952:968	WTA glycosylation	952:968	Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus.
29382892	5	69	theme	Whole	832:836	arg1	Fourier					843:849	Whole cell Fourier	832:849	Whole cell Fourier transform infrared (FTIR) spectroscopy	832:888	Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus.
29382892	2	70	theme	α-/β-O-GlcNAc	436:448	arg1	residues					451:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues	393:458	Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or β-O-linked N-acetyl-glucosamine (α-/β-O-GlcNAc) residues.
29382892	8	71	dep	represents	1364:1373	arg1	opening					1458:1464	opening	1458:1464	opening	1458:1464	Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
29382892	6	72	theme	expression	1046:1055	arg1	loss					1034:1037	a complete loss	1023:1037	a complete loss of WTA expression	1023:1055	Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules.
31785521	1	0	theme	2-hydroxy-5-sulfonatobenzyl	635:661	arg1	N					494:494	N	494:494	N	494:494	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	0	theme	2-hydroxy-5-sulfonatobenzyl	635:661	arg1	BuHSS					683:687	BuHSS	683:687	BuHSS	683:687	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	0	theme	2-hydroxy-5-sulfonatobenzyl	635:661	arg1	-1,4-diaminobutane					663:680	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane	628:680	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)	628:688	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	1	theme	N'-bis	559:564	arg1	N					494:494	N	494:494	N	494:494	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	1	theme	N'-bis	559:564	arg1	PrHSS					615:619	PrHSS	615:619	PrHSS	615:619	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	1	theme	N'-bis	559:564	arg1	-1,4-diaminopropane					594:612	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane	559:612	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS)	559:620	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	7	2	theme	salan	1567:1571	arg1	moiety					1573:1578	sulfonated salan moiety	1556:1578	sulfonated salan moiety	1556:1578	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	4	3	theme	system	1133:1138	arg1	formation					1093:1101	the formation	1089:1101	the formation of (O-,N,N,O-) linked chelate system	1089:1138	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	2	4	theme	metal	764:768	arg1	complexes					770:778	the metal complexes	760:778	the metal complexes	760:778	The stability constants of the metal complexes were determined using pH-potentiometry.
31785521	1	5	theme	biological	207:216	arg1	membranes					218:226	biological membranes	207:226	biological membranes	207:226	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	0	6	theme	Ni	66:67	arg1	applications					37:48	Coordination chemistry and catalytic applications	0:48	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)	0:71	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)-sulfosalan complexes in aqueous media.
31785521	3	7	theme	oct-1-en-3-ol	930:942	arg1	hydrogenation					889:901	hydrogenation	889:901	hydrogenation	889:901	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	7	theme	oct-1-en-3-ol	930:942	arg1	isomerization					913:925	redox isomerization	907:925	redox isomerization of oct-1-en-3-ol	907:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	1	8	theme	2-hydroxy-5-sulfonatobenzyl	566:592	arg1	N					494:494	N	494:494	N	494:494	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	8	theme	2-hydroxy-5-sulfonatobenzyl	566:592	arg1	PrHSS					615:619	PrHSS	615:619	PrHSS	615:619	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	8	theme	2-hydroxy-5-sulfonatobenzyl	566:592	arg1	-1,4-diaminopropane					594:612	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane	559:612	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS)	559:620	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	9	theme	membranes	218:226	arg1	modification					191:202	modification	191:202	modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions	191:301	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	3	10	theme	redox	907:911	arg1	isomerization					913:925	redox isomerization	907:925	redox isomerization of oct-1-en-3-ol	907:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	4	11	theme	excellent	1030:1038	arg1	ability					1077:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	5	12	dep	hydrogenation	1183:1195	arg1	the					1179:1181	the	1179:1181	the	1179:1181	Both [Ni(HSS)] and [Pd(HSS)] catalyze the hydrogenation and redox isomerization of oct-1-en-3-ol.
31785521	3	13	theme	[Ni	852:854	arg1	activities					834:843	The catalytic activities	820:843	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol	820:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	1	14	theme	detailed	322:329	arg1	equilibrium					331:341	detailed equilibrium	322:341	detailed equilibrium	322:341	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	2	15	theme	complexes	770:778	arg1	constants					747:755	The stability constants	733:755	The stability constants of the metal complexes	733:778	The stability constants of the metal complexes were determined using pH-potentiometry.
31785521	3	16	from	activities	834:843	arg1	hydrogenation					889:901	hydrogenation	889:901	hydrogenation	889:901	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	16	from	activities	834:843	arg1	isomerization					913:925	redox isomerization	907:925	redox isomerization of oct-1-en-3-ol	907:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	4	17	theme	nickel	1040:1045	arg1	ability					1077:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	1	18	from	rings	487:491	arg1	range					726:730	the slightly acidic-alkaline pH range	694:730	the slightly acidic-alkaline pH range	694:730	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	7	19	theme	active	1365:1370	arg1	[Ni					1344:1346	[Ni	1344:1346	[Ni(HSS)]	1344:1352	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	7	19	theme	active	1365:1370	arg1	catalyst					1386:1393	an active and selective catalyst	1362:1393	an active and selective catalyst for this hydrogenation reaction	1362:1425	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	5	20	theme	redox	1201:1205	arg1	isomerization					1207:1219	redox isomerization	1201:1219	redox isomerization	1201:1219	Both [Ni(HSS)] and [Pd(HSS)] catalyze the hydrogenation and redox isomerization of oct-1-en-3-ol.
31785521	0	21	from	complexes	84:92	arg1	media					105:109	aqueous media	97:109	aqueous media	97:109	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)-sulfosalan complexes in aqueous media.
31785521	1	22	theme	N'-bis	496:501	arg1	HSS					551:553	HSS	551:553	HSS	551:553	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	22	theme	N'-bis	496:501	arg1	-1,4-diaminoethane					531:548	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane	496:548	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS)	496:554	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	22	theme	N'-bis	496:501	arg1	N					494:494	N	494:494	N	494:494	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	0	23	theme	chemistry	13:21	arg1	applications					37:48	Coordination chemistry and catalytic applications	0:48	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)	0:71	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)-sulfosalan complexes in aqueous media.
31785521	0	24	theme	aqueous	97:103	arg1	media					105:109	aqueous media	97:109	aqueous media	97:109	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)-sulfosalan complexes in aqueous media.
31785521	3	25	from	hydrogenation	889:901	arg1	HSS					856:858	HSS	856:858	HSS	856:858	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	25	from	hydrogenation	889:901	arg1	activities					834:843	The catalytic activities	820:843	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol	820:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	25	from	hydrogenation	889:901	arg1	[Ni					852:854	[Ni	852:854	[Ni	852:854	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	1	26	theme	homogeneous	231:241	arg1	hydrogenation					243:255	homogeneous hydrogenation	231:255	homogeneous hydrogenation in aqueous solution and under mild conditions	231:301	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	27	from	hydrogenation	243:255	arg1	solution					268:275	aqueous solution	260:275	aqueous solution	260:275	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	7	28	theme	first	1478:1482	arg1	catalyst					1539:1546	the first nickel(II)-based, hydrolytically stable, water-soluble catalyst	1474:1546	the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety	1474:1578	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	7	28	theme	first	1478:1482	arg1	[Ni					1461:1463	[Ni	1461:1463	[Ni(HSS)]	1461:1469	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	1	29	theme	2-hydroxy-5-sulfonatobenzyl	503:529	arg1	HSS					551:553	HSS	551:553	HSS	551:553	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	29	theme	2-hydroxy-5-sulfonatobenzyl	503:529	arg1	-1,4-diaminoethane					531:548	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane	496:548	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS)	496:554	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	29	theme	2-hydroxy-5-sulfonatobenzyl	503:529	arg1	N					494:494	N	494:494	N	494:494	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	0	30	theme	catalytic	27:35	arg1	applications					37:48	Coordination chemistry and catalytic applications	0:48	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)	0:71	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)-sulfosalan complexes in aqueous media.
31785521	7	31	theme	hydrogenation	1404:1416	arg1	reaction					1418:1425	this hydrogenation reaction	1399:1425	this hydrogenation reaction	1399:1425	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	5	32	theme	oct-1-en-3-ol	1224:1236	arg1	hydrogenation					1183:1195	hydrogenation	1183:1195	hydrogenation	1183:1195	Both [Ni(HSS)] and [Pd(HSS)] catalyze the hydrogenation and redox isomerization of oct-1-en-3-ol.
31785521	5	32	theme	oct-1-en-3-ol	1224:1236	arg1	isomerization					1207:1219	redox isomerization	1201:1219	redox isomerization	1201:1219	Both [Ni(HSS)] and [Pd(HSS)] catalyze the hydrogenation and redox isomerization of oct-1-en-3-ol.
31785521	3	33	theme	[Pd	866:868	arg1	HSS					870:872	HSS	870:872	HSS	870:872	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	33	theme	[Pd	866:868	arg1	complexes					876:884	the [Ni(HSS)] and [Pd(HSS)] complexes	848:884	complexes	876:884	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	1	34	theme	new	140:142	arg1	types					144:148	new types	140:148	new types of water-soluble catalyst precursors	140:185	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	35	theme	spectroscopic	347:359	arg1	characterization					361:376	spectroscopic characterization	347:376	spectroscopic characterization	347:376	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	4	36	theme	binding	1069:1075	arg1	ability					1077:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	1	37	dep	rings	487:491	arg1	N					557:557	N	557:557	N	557:557	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	37	dep	rings	487:491	arg1	-1,4-diaminopropane					594:612	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane	559:612	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS)	559:620	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	37	dep	rings	487:491	arg1	-1,4-diaminoethane					531:548	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane	496:548	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS)	496:554	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	37	dep	rings	487:491	arg1	N					494:494	N	494:494	N	494:494	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	37	dep	rings	487:491	arg1	N					626:626	N	626:626	N	626:626	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	37	dep	rings	487:491	arg1	-1,4-diaminobutane					663:680	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane	628:680	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)	628:688	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	38	theme	aqueous	260:266	arg1	solution					268:275	aqueous solution	260:275	aqueous solution	260:275	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	4	39	theme	linked	1118:1123	arg1	system					1133:1138	(O-,N,N,O-) linked chelate system	1106:1138	(O-,N,N,O-) linked chelate system	1106:1138	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	4	40	dep	system	1133:1138	arg1	N					1110:1110	N	1110:1110	N	1110:1110	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	4	40	dep	system	1133:1138	arg1	O-					1107:1108	O-	1107:1108	O-	1107:1108	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	7	41	theme	-based	1494:1499	arg1	catalyst					1539:1546	the first nickel(II)-based, hydrolytically stable, water-soluble catalyst	1474:1546	the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety	1474:1578	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	7	41	theme	-based	1494:1499	arg1	[Ni					1461:1463	[Ni	1461:1463	[Ni(HSS)]	1461:1469	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	1	42	theme	salan-type	439:448	arg1	ligands					450:456	salan-type ligands	439:456	salan-type ligands	439:456	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	43	theme	water-soluble	153:165	arg1	precursors					176:185	water-soluble catalyst precursors	153:185	water-soluble catalyst precursors	153:185	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	7	44	theme	selective	1376:1384	arg1	[Ni					1344:1346	[Ni	1344:1346	[Ni(HSS)]	1344:1352	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	7	44	theme	selective	1376:1384	arg1	catalyst					1386:1393	an active and selective catalyst	1362:1393	an active and selective catalyst for this hydrogenation reaction	1362:1425	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	1	45	theme	acidic-alkaline	707:721	arg1	range					726:730	the slightly acidic-alkaline pH range	694:730	the slightly acidic-alkaline pH range	694:730	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	46	theme	complex	381:387	arg1	formation					389:397	complex formation	381:397	complex formation	381:397	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	0	47	theme	Pd	53:54	arg1	applications					37:48	Coordination chemistry and catalytic applications	0:48	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)	0:71	Coordination chemistry and catalytic applications of Pd(II)-, and Ni(II)-sulfosalan complexes in aqueous media.
31785521	4	48	theme	chelate	1125:1131	arg1	system					1133:1138	(O-,N,N,O-) linked chelate system	1106:1138	(O-,N,N,O-) linked chelate system	1106:1138	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	1	49	theme	pH	723:724	arg1	range					726:730	the slightly acidic-alkaline pH range	694:730	the slightly acidic-alkaline pH range	694:730	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	50	theme	formation	389:397	arg1	equilibrium					331:341	detailed equilibrium	322:341	detailed equilibrium	322:341	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	50	theme	formation	389:397	arg1	characterization					361:376	spectroscopic characterization	347:376	spectroscopic characterization	347:376	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	6	51	theme	octan-3-ol	1332:1341	arg1	formation					1319:1327	the formation	1315:1327	the formation of octan-3-ol	1315:1341	[Pd(HSS)] shows excellent activity and the reaction was highly selective to the formation of octan-3-ol.
31785521	1	52	theme	mild	287:290	arg1	conditions					292:301	mild conditions	287:301	mild conditions	287:301	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	7	53	theme	sulfonated	1556:1565	arg1	moiety					1573:1578	sulfonated salan moiety	1556:1578	sulfonated salan moiety	1556:1578	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	7	54	dep	-based	1494:1499	arg1	water-soluble					1525:1537	water-soluble	1525:1537	water-soluble	1525:1537	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	7	54	dep	-based	1494:1499	arg1	stable					1517:1522	stable	1517:1522	stable	1517:1522	[Ni(HSS)] is also an active and selective catalyst for this hydrogenation reaction and to the best of our knowledge, [Ni(HSS)] is the first nickel(II)-based, hydrolytically stable, water-soluble catalyst bearing sulfonated salan moiety.
31785521	1	55	theme	catalyst	167:174	arg1	precursors					176:185	water-soluble catalyst precursors	153:185	water-soluble catalyst precursors	153:185	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	3	56	from	[Ni	852:854	arg1	hydrogenation					889:901	hydrogenation	889:901	hydrogenation	889:901	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	56	from	[Ni	852:854	arg1	isomerization					913:925	redox isomerization	907:925	redox isomerization of oct-1-en-3-ol	907:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	4	57	theme	palladium	1055:1063	arg1	ability					1077:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	excellent nickel(II) and palladium(II) binding ability	1030:1083	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	4	58	theme	investigated	1001:1012	arg1	ligands					1014:1020	the investigated ligands	997:1020	the investigated ligands	997:1020	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
31785521	2	59	theme	stability	737:745	arg1	constants					747:755	The stability constants	733:755	The stability constants of the metal complexes	733:778	The stability constants of the metal complexes were determined using pH-potentiometry.
31785521	1	60	theme	precursors	176:185	arg1	types					144:148	new types	140:148	new types of water-soluble catalyst precursors	140:185	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	61	theme	N'-bis	628:633	arg1	N					494:494	N	494:494	N	494:494	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	61	theme	N'-bis	628:633	arg1	BuHSS					683:687	BuHSS	683:687	BuHSS	683:687	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	1	61	theme	N'-bis	628:633	arg1	-1,4-diaminobutane					663:680	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane	628:680	N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)	628:688	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	3	62	theme	catalytic	824:832	arg1	activities					834:843	The catalytic activities	820:843	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol	820:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	1	63	theme	aromatic	478:485	arg1	rings					487:491	their aromatic rings	472:491	their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range	472:730	With the aim of identifying new types of water-soluble catalyst precursors for modification of biological membranes by homogeneous hydrogenation in aqueous solution and under mild conditions, we have performed detailed equilibrium and spectroscopic characterization of complex formation between nickel(II) or palladium(II) and salan-type ligands sulfonated in their aromatic rings (N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminoethane (HSS), N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminopropane (PrHSS) and N,N'-bis(2-hydroxy-5-sulfonatobenzyl)-1,4-diaminobutane (BuHSS)) in the slightly acidic-alkaline pH range.
31785521	3	64	theme	complexes	876:884	arg1	activities					834:843	The catalytic activities	820:843	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol	820:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	65	from	isomerization	913:925	arg1	HSS					856:858	HSS	856:858	HSS	856:858	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	65	from	isomerization	913:925	arg1	activities					834:843	The catalytic activities	820:843	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol	820:942	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	3	65	from	isomerization	913:925	arg1	[Ni					852:854	[Ni	852:854	[Ni	852:854	The catalytic activities of the [Ni(HSS)] and [Pd(HSS)] complexes in hydrogenation and redox isomerization of oct-1-en-3-ol were also studied.
31785521	6	66	theme	excellent	1255:1263	arg1	activity					1265:1272	excellent activity	1255:1272	excellent activity	1255:1272	[Pd(HSS)] shows excellent activity and the reaction was highly selective to the formation of octan-3-ol.
31785521	4	67	link	linked	1118:1123	arg1	system					1133:1138	(O-,N,N,O-) linked chelate system	1106:1138	(O-,N,N,O-) linked chelate system	1106:1138	The results indicate, that all of the investigated ligands exhibit excellent nickel(II) and palladium(II) binding ability via the formation of (O-,N,N,O-) linked chelate system.
30292807	2	0	theme	Tx4	506:508	arg1	expression					480:489	secretory expression	470:489	secretory expression of recombinant Tx4(6-1)	470:513	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	2	1	theme	immunosorbent	608:620	arg1	ELISA					629:633	ELISA	629:633	ELISA	629:633	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	2	1	theme	immunosorbent	608:620	arg1	assay					622:626	enzyme-linked immunosorbent assay	594:626	enzyme-linked immunosorbent assay (ELISA)	594:634	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	5	2	theme	mass	1064:1067	arg1	MS					1083:1084	MS	1083:1084	MS	1083:1084	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	5	2	theme	mass	1064:1067	arg1	spectrometry					1069:1080	mass spectrometry	1064:1080	mass spectrometry (MS) analysis	1064:1094	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	0	3	dep	in	119:120	arg1	vivo					122:125	vivo	122:125	vivo	122:125	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	4	4	theme	ion-exchange	998:1009	arg1	chromatography					1011:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	1	5	theme	reversed-phase	231:244	arg1	fractionation					292:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation	231:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4	231:313	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	2	6	theme	recombinant	494:504	arg1	6-1					510:512	6-1	510:512	6-1	510:512	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	2	6	theme	recombinant	494:504	arg1	Tx4					506:508	recombinant Tx4	494:508	recombinant Tx4(6-1)	494:513	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	0	7	from	production	11:20	arg1	pastoris					87:94	Pichia pastoris	80:94	Pichia pastoris	80:94	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	2	8	theme	enzyme-linked	594:606	arg1	ELISA					629:633	ELISA	629:633	ELISA	629:633	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	2	8	theme	enzyme-linked	594:606	arg1	assay					622:626	enzyme-linked immunosorbent assay	594:626	enzyme-linked immunosorbent assay (ELISA)	594:634	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	6	9	theme	half	1421:1424	arg1	dose					1433:1436	a half lethal dose	1419:1436	a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight	1419:1488	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	1	10	theme	high-performance	246:261	arg1	fractionation					292:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation	231:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4	231:313	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	4	11	theme	culture	886:892	arg1	supernatant					894:904	a 400 ml fed-batch culture supernatant	867:904	a 400 ml fed-batch culture supernatant	867:904	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	4	12	theme	rTx4	839:842	arg1	4 mg					819:822	Approximately 4 mg	805:822	Approximately 4 mg of high-purity rTx4(6-1)	805:847	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	5	13	theme	O-linked	1182:1189	arg1	glycosylation					1191:1203	O-linked glycosylation	1182:1203	O-linked glycosylation	1182:1203	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	1	14	theme	liquid-chromatography	263:283	arg1	fractionation					292:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation	231:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4	231:313	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	0	15	theme	Pichia	80:85	arg1	pastoris					87:94	Pichia pastoris	80:94	Pichia pastoris	80:94	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	4	16	theme	high-purity	827:837	arg1	6-1					844:846	6-1	844:846	6-1	844:846	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	4	16	theme	high-purity	827:837	arg1	rTx4					839:842	high-purity rTx4	827:842	high-purity rTx4(6-1)	827:847	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	1	17	theme	neurotoxin	153:162	arg1	6-1					168:170	6-1	168:170	6-1	168:170	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	1	17	theme	neurotoxin	153:162	arg1	Tx4					164:166	Short-chain insecticidal neurotoxin Tx4	128:166	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer	128:210	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	0	18	theme	bioactivity	100:110	arg1	assays					112:117	bioactivity assays	100:117	bioactivity assays in vivo	100:125	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	6	19	theme	∼4.5-8.5 μg/g	1464:1476	arg1	weight					1483:1488	∼4.5-8.5 μg/g body weight	1464:1488	∼4.5-8.5 μg/g body weight	1464:1488	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	20	theme	neurotoxin	1311:1320	arg1	syndrome					1404:1411	mouth movement syndrome	1389:1411	mouth movement syndrome	1389:1411	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	20	theme	neurotoxin	1311:1320	arg1	contraction					1372:1382	abdominal contraction	1362:1382	abdominal contraction	1362:1382	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	20	theme	neurotoxin	1311:1320	arg1	symptoms					1322:1329	neurotoxin symptoms	1311:1329	neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome	1311:1411	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	20	theme	neurotoxin	1311:1320	arg1	paralysis					1351:1359	contraction paralysis	1339:1359	contraction paralysis	1339:1359	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	3	21	with	induction	712:720	arg1	methanol					727:734	methanol	727:734	methanol	727:734	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	6	22	from	post-injection	1446:1459	arg1	dose					1433:1436	a half lethal dose	1419:1436	a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight	1419:1488	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	4	23	theme	400 ml	869:874	arg1	supernatant					894:904	a 400 ml fed-batch culture supernatant	867:904	a 400 ml fed-batch culture supernatant	867:904	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	6	24	theme	larvae	1274:1279	arg1	tests					1225:1229	Insect bioactivity tests	1206:1229	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus)	1206:1302	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	4	25	theme	CM	984:985	arg1	chromatography					1011:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	3	26	theme	secreted	685:692	arg1	rTx4					656:659	∼5 mg/l rTx4	648:659	∼5 mg/l rTx4(6-1)	648:664	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	3	26	theme	secreted	685:692	arg1	protein					694:700	a secreted protein	683:700	a secreted protein	683:700	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	3	27	theme	∼5 mg/l	648:654	arg1	rTx4					656:659	∼5 mg/l rTx4	648:659	∼5 mg/l rTx4(6-1)	648:664	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	3	27	theme	∼5 mg/l	648:654	arg1	protein					694:700	a secreted protein	683:700	a secreted protein	683:700	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	3	27	theme	∼5 mg/l	648:654	arg1	6-1					661:663	6-1	661:663	6-1	661:663	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	5	28	theme	molecular	1109:1117	arg1	weight					1119:1124	a molecular weight	1107:1124	a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation	1107:1203	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	5	28	theme	molecular	1109:1117	arg1	MW					1127:1128	MW	1127:1128	MW	1127:1128	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	0	29	theme	High-yield	0:9	arg1	production					11:20	High-yield production	0:20	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris	0:94	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	1	30	theme	HPLC	286:289	arg1	fractionation					292:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation	231:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4	231:313	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	4	31	theme	carboxymethyl	969:981	arg1	chromatography					1011:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	6	32	theme	Insect	1206:1211	arg1	tests					1225:1229	Insect bioactivity tests	1206:1229	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus)	1206:1302	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	0	33	theme	spider	25:30	arg1	6-1					72:74	6-1	72:74	6-1	72:74	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	0	33	theme	spider	25:30	arg1	Tx4					68:70	spider short-chain insecticidal neurotoxin Tx4	25:70	spider short-chain insecticidal neurotoxin Tx4(6-1)	25:75	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	0	34	theme	in	119:120	arg1	assays					112:117	bioactivity assays	100:117	bioactivity assays in vivo	100:125	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	6	35	theme	mori	1289:1292	arg1	Linnaeus					1294:1301	Bombyx mori Linnaeus	1282:1301	Bombyx mori Linnaeus	1282:1301	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	35	theme	mori	1289:1292	arg1	larvae					1274:1279	rTx4(6-1)-treated fifth-instar silkworm larvae	1234:1279	rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus)	1234:1302	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	36	theme	lethal	1426:1431	arg1	dose					1433:1436	a half lethal dose	1419:1436	a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight	1419:1488	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	37	theme	contraction	1339:1349	arg1	paralysis					1351:1359	contraction paralysis	1339:1359	contraction paralysis	1339:1359	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	38	theme	-treated	1243:1250	arg1	Linnaeus					1294:1301	Bombyx mori Linnaeus	1282:1301	Bombyx mori Linnaeus	1282:1301	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	38	theme	-treated	1243:1250	arg1	larvae					1274:1279	rTx4(6-1)-treated fifth-instar silkworm larvae	1234:1279	rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus)	1234:1302	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	5	39	theme	expected	1161:1168	arg1	size					1170:1173	the expected size	1157:1173	the expected size due to O-linked glycosylation	1157:1203	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	1	40	theme	spider	182:187	arg1	nigriventer					200:210	the spider Phoneutria nigriventer	178:210	the spider Phoneutria nigriventer	178:210	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	0	41	theme	insecticidal	44:55	arg1	6-1					72:74	6-1	72:74	6-1	72:74	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	0	41	theme	insecticidal	44:55	arg1	Tx4					68:70	spider short-chain insecticidal neurotoxin Tx4	25:70	spider short-chain insecticidal neurotoxin Tx4(6-1)	25:75	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	2	42	dep	pastoris	528:535	arg1	strain					537:542	strain X33	537:546	Pichia pastoris strain X33	521:546	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	5	43	link	O-linked	1182:1189	arg1	glycosylation					1191:1203	O-linked glycosylation	1182:1203	O-linked glycosylation	1182:1203	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	6	44	theme	bioactivity	1213:1223	arg1	tests					1225:1229	Insect bioactivity tests	1206:1229	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus)	1206:1302	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	45	theme	movement	1395:1402	arg1	syndrome					1404:1411	mouth movement syndrome	1389:1411	mouth movement syndrome	1389:1411	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	1	46	theme	Phoneutria	189:198	arg1	nigriventer					200:210	the spider Phoneutria nigriventer	178:210	the spider Phoneutria nigriventer	178:210	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	0	47	theme	short-chain	32:42	arg1	6-1					72:74	6-1	72:74	6-1	72:74	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	0	47	theme	short-chain	32:42	arg1	Tx4					68:70	spider short-chain insecticidal neurotoxin Tx4	25:70	spider short-chain insecticidal neurotoxin Tx4(6-1)	25:75	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	1	48	theme	PhTx4	309:313	arg1	fractionation					292:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation	231:304	reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4	231:313	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	1	49	theme	insecticidal	392:403	arg1	activity					405:412	its insecticidal activity	388:412	its insecticidal activity against agricultural insect pests	388:446	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	4	50	theme	sepharose	988:996	arg1	chromatography					1011:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	carboxymethyl (CM) sepharose ion-exchange chromatography	969:1024	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	6	51	theme	silkworm	1265:1272	arg1	Linnaeus					1294:1301	Bombyx mori Linnaeus	1282:1301	Bombyx mori Linnaeus	1282:1301	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	51	theme	silkworm	1265:1272	arg1	larvae					1274:1279	rTx4(6-1)-treated fifth-instar silkworm larvae	1234:1279	rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus)	1234:1302	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	0	52	theme	Tx4	68:70	arg1	assays					112:117	bioactivity assays	100:117	bioactivity assays in vivo	100:125	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	0	52	theme	Tx4	68:70	arg1	production					11:20	High-yield production	0:20	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris	0:94	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	6	53	theme	Bombyx	1282:1287	arg1	Linnaeus					1294:1301	Bombyx mori Linnaeus	1282:1301	Bombyx mori Linnaeus	1282:1301	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	6	53	theme	Bombyx	1282:1287	arg1	larvae					1274:1279	rTx4(6-1)-treated fifth-instar silkworm larvae	1234:1279	rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus)	1234:1302	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	1	54	theme	activity	405:412	arg1	analyses					376:383	analyses	376:383	analyses of its insecticidal activity against agricultural insect pests	376:446	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	2	55	theme	Pichia	521:526	arg1	host					555:558	the host	551:558	the host	551:558	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	2	55	theme	Pichia	521:526	arg1	pastoris					528:535	Pichia pastoris	521:535	Pichia pastoris strain X33	521:546	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	1	56	from	nigriventer	200:210	arg1	6-1					168:170	6-1	168:170	6-1	168:170	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	1	56	from	nigriventer	200:210	arg1	Tx4					164:166	Short-chain insecticidal neurotoxin Tx4	128:166	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer	128:210	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	6	57	dep	-treated	1243:1250	arg1	fifth-instar					1252:1263	fifth-instar	1252:1263	fifth-instar	1252:1263	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	0	58	theme	neurotoxin	57:66	arg1	6-1					72:74	6-1	72:74	6-1	72:74	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	0	58	theme	neurotoxin	57:66	arg1	Tx4					68:70	spider short-chain insecticidal neurotoxin Tx4	25:70	spider short-chain insecticidal neurotoxin Tx4(6-1)	25:75	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
30292807	4	59	theme	Ni+-nitriloacetic	909:925	arg1	chromatography					941:954	Ni+-nitriloacetic acid affinity chromatography	909:954	Ni+-nitriloacetic acid affinity chromatography	909:954	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	1	60	theme	agricultural	422:433	arg1	pests					442:446	agricultural insect pests	422:446	agricultural insect pests	422:446	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	5	61	theme	7660.5 Da	1134:1142	arg1	weight					1119:1124	a molecular weight	1107:1124	a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation	1107:1203	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	5	61	theme	7660.5 Da	1134:1142	arg1	MW					1127:1128	MW	1127:1128	MW	1127:1128	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	6	62	theme	abdominal	1362:1370	arg1	contraction					1372:1382	abdominal contraction	1362:1382	abdominal contraction	1362:1382	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	7	63	theme	silkworm	1528:1535	arg1	larvae					1537:1542	silkworm larvae	1528:1542	silkworm larvae	1528:1542	Dietary toxicity was not observed in silkworm larvae.
30292807	4	64	theme	affinity	932:939	arg1	chromatography					941:954	Ni+-nitriloacetic acid affinity chromatography	909:954	Ni+-nitriloacetic acid affinity chromatography	909:954	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	7	65	located	observed	1516:1523	arg2	toxicity					1499:1506	Dietary toxicity	1491:1506	Dietary toxicity	1491:1506	Dietary toxicity was not observed in silkworm larvae.
30292807	7	65	located	observed	1516:1523	arg1	larvae					1537:1542	silkworm larvae	1528:1542	silkworm larvae	1528:1542	Dietary toxicity was not observed in silkworm larvae.
30292807	1	66	theme	insect	435:440	arg1	pests					442:446	agricultural insect pests	422:446	agricultural insect pests	422:446	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	4	67	theme	fed-batch	876:884	arg1	supernatant					894:904	a 400 ml fed-batch culture supernatant	867:904	a 400 ml fed-batch culture supernatant	867:904	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	3	68	theme	fed-batch	786:794	arg1	reactor					796:802	a fed-batch reactor	784:802	a fed-batch reactor	784:802	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	6	69	theme	12 h	1441:1444	arg1	post-injection					1446:1459	12 h post-injection	1441:1459	12 h post-injection	1441:1459	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	4	70	theme	acid	927:930	arg1	chromatography					941:954	Ni+-nitriloacetic acid affinity chromatography	909:954	Ni+-nitriloacetic acid affinity chromatography	909:954	Approximately 4 mg of high-purity rTx4(6-1) was purified from a 400 ml fed-batch culture supernatant by Ni+-nitriloacetic acid affinity chromatography, followed by carboxymethyl (CM) sepharose ion-exchange chromatography.
30292807	5	71	theme	Purified	1027:1034	arg1	6-1					1041:1043	6-1	1041:1043	6-1	1041:1043	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	5	71	theme	Purified	1027:1034	arg1	rTx4					1036:1039	Purified rTx4	1027:1039	Purified rTx4(6-1)	1027:1044	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	6	72	theme	weight	1483:1488	arg1	dose					1433:1436	a half lethal dose	1419:1436	a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight	1419:1488	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	1	73	theme	Short-chain	128:138	arg1	6-1					168:170	6-1	168:170	6-1	168:170	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	1	73	theme	Short-chain	128:138	arg1	Tx4					164:166	Short-chain insecticidal neurotoxin Tx4	128:166	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer	128:210	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	2	74	link	enzyme-linked	594:606	arg1	ELISA					629:633	ELISA	629:633	ELISA	629:633	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	2	74	link	enzyme-linked	594:606	arg1	assay					622:626	enzyme-linked immunosorbent assay	594:626	enzyme-linked immunosorbent assay (ELISA)	594:634	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	7	75	theme	Dietary	1491:1497	arg1	toxicity					1499:1506	Dietary toxicity	1491:1506	Dietary toxicity	1491:1506	Dietary toxicity was not observed in silkworm larvae.
30292807	2	76	theme	secretory	470:478	arg1	expression					480:489	secretory expression	470:489	secretory expression of recombinant Tx4(6-1)	470:513	Herein, we performed secretory expression of recombinant Tx4(6-1) using Pichia pastoris strain X33 as the host, and screened transformants using enzyme-linked immunosorbent assay (ELISA).
30292807	5	77	theme	spectrometry	1069:1080	arg1	analysis					1087:1094	mass spectrometry (MS) analysis	1064:1094	mass spectrometry (MS) analysis	1064:1094	Purified rTx4(6-1) was determined by mass spectrometry (MS) analysis, revealing a molecular weight (MW) of 7660.5 Da, larger than the expected size due to O-linked glycosylation.
30292807	3	78	theme	45 mg/l	763:769	arg1	rTx4					771:774	45 mg/l rTx4	763:774	45 mg/l rTx4(6-1)	763:779	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	3	78	theme	45 mg/l	763:769	arg1	6-1					776:778	6-1	776:778	6-1	776:778	In flasks, ∼5 mg/l rTx4(6-1) was expressed as a secreted protein following induction with methanol, and this was increased to 45 mg/l rTx4(6-1) in a fed-batch reactor.
30292807	6	79	theme	body	1478:1481	arg1	weight					1483:1488	∼4.5-8.5 μg/g body weight	1464:1488	∼4.5-8.5 μg/g body weight	1464:1488	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	1	80	theme	insecticidal	140:151	arg1	6-1					168:170	6-1	168:170	6-1	168:170	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	1	80	theme	insecticidal	140:151	arg1	Tx4					164:166	Short-chain insecticidal neurotoxin Tx4	128:166	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer	128:210	Short-chain insecticidal neurotoxin Tx4(6-1) from the spider Phoneutria nigriventer can be prepared by reversed-phase high-performance liquid-chromatography (HPLC) fractionation of PhTx4, but this is difficult and represents an obstacle preventing analyses of its insecticidal activity against agricultural insect pests.
30292807	6	81	theme	mouth	1389:1393	arg1	syndrome					1404:1411	mouth movement syndrome	1389:1411	mouth movement syndrome	1389:1411	Insect bioactivity tests of rTx4(6-1)-treated fifth-instar silkworm larvae (Bombyx mori Linnaeus) showed neurotoxin symptoms such as contraction paralysis, abdominal contraction, and mouth movement syndrome, with a half lethal dose at 12 h post-injection of ∼4.5-8.5 μg/g body weight.
30292807	0	82	from	assays	112:117	arg1	pastoris					87:94	Pichia pastoris	80:94	Pichia pastoris	80:94	High-yield production of spider short-chain insecticidal neurotoxin Tx4(6-1) in Pichia pastoris and bioactivity assays in vivo.
29756380	6	0	from	levels	1171:1176	arg1	tissues					1213:1219	peripheral tissues	1202:1219	peripheral tissues of mammals	1202:1230	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	1	1	theme	threonine	172:180	arg1	glycosylation					144:156	O-Linked glycosylation	135:156	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues	135:264	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	1	2	theme	O-GlcNAc	282:289	arg1	transferase					291:301	O-GlcNAc transferase	282:301	O-GlcNAc transferase (OGT)	282:307	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	1	2	theme	O-GlcNAc	282:289	arg1	OGT					304:306	OGT	304:306	OGT	304:306	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	0	3	theme	O-GlcNAc	82:89	arg1	Levels					91:96	Decreased O-GlcNAc Levels	72:96	Decreased O-GlcNAc Levels	72:96	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.
29756380	4	4	theme	5-thiosugar	525:535	arg1	analogues					537:545	These 5-thiosugar analogues	519:545	These 5-thiosugar analogues of N-acetylglucosamine	519:568	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29756380	2	5	theme	wide	370:373	arg1	range					375:379	a wide range	368:379	a wide range of physiological processes	368:406	O-GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes.
29756380	4	6	theme	metabolic	607:615	arg1	pathway					617:623	a convergent metabolic pathway	594:623	a convergent metabolic pathway	594:623	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29756380	0	7	theme	Leptin-Mediated	101:115	arg1	Sensing					126:132	Leptin-Mediated Nutrient Sensing	101:132	Leptin-Mediated Nutrient Sensing	101:132	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.
29756380	6	8	from	sensing	1191:1197	arg1	tissues					1213:1219	peripheral tissues	1202:1219	peripheral tissues of mammals	1202:1230	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	6	9	theme	O-GlcNAc	1162:1169	arg1	levels					1171:1176	decreased O-GlcNAc levels	1152:1176	decreased O-GlcNAc levels	1152:1176	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	5	10	theme	various	926:932	arg1	tissues					934:940	various tissues	926:940	various tissues	926:940	We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues.
29756380	5	11	from	decreases	894:902	arg1	levels					916:921	O-GlcNAc levels	907:921	O-GlcNAc levels in various tissues	907:940	We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues.
29756380	1	12	with	glycosylation	144:156	arg1	residues					257:264	N-acetylglucosamine (O-GlcNAc) residues	226:264	N-acetylglucosamine (O-GlcNAc) residues	226:264	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	5	13	theme	O-GlcNAc	907:914	arg1	levels					916:921	O-GlcNAc levels	907:921	O-GlcNAc levels in various tissues	907:940	We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues.
29756380	4	14	theme	common	717:722	arg1	inhibitor					728:736	a common OGT inhibitor	715:736	a common OGT inhibitor	715:736	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29756380	3	15	theme	OGT	463:465	arg1	inhibitors					449:458	metabolic precursor inhibitors	429:458	metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice	429:516	Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice.
29756380	0	16	theme	Nutrient	117:124	arg1	Sensing					126:132	Leptin-Mediated Nutrient Sensing	101:132	Leptin-Mediated Nutrient Sensing	101:132	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.
29756380	6	17	theme	factor	1070:1075	arg1	Sp1					1077:1079	the transcription factor Sp1	1052:1079	the transcription factor Sp1	1052:1079	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	3	18	from	cells	492:496	arg1	mice					513:516	mice	513:516	mice	513:516	Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice.
29756380	1	19	theme	nucleocytoplasmic	194:210	arg1	proteins					212:219	nucleocytoplasmic proteins	194:219	nucleocytoplasmic proteins	194:219	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	5	20	theme	dose-	869:873	arg1	decreases					894:902	dose- and time-dependent decreases	869:902	dose- and time-dependent decreases in O-GlcNAc levels in various tissues	869:940	We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues.
29756380	1	21	theme	proteins	212:219	arg1	threonine					172:180	threonine	172:180	threonine	172:180	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	1	21	theme	proteins	212:219	arg1	serine					161:166	serine	161:166	serine	161:166	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	0	22	theme	Metabolic	0:8	arg1	Inhibitors					10:19	Metabolic Inhibitors	0:19	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo	0:60	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.
29756380	3	23	from	in vivo	502:508	arg1	mice					513:516	mice	513:516	mice	513:516	Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice.
29756380	6	24	theme	mammals	1224:1230	arg1	tissues					1213:1219	peripheral tissues	1202:1219	peripheral tissues of mammals	1202:1230	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	2	25	theme	processes	398:406	arg1	range					375:379	a wide range	368:379	a wide range of physiological processes	368:406	O-GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes.
29756380	0	26	theme	O-GlcNAc	24:31	arg1	Transferase					33:43	O-GlcNAc Transferase	24:43	O-GlcNAc Transferase That Act In Vivo	24:60	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.
29756380	6	27	theme	lower	1036:1040	arg1	levels					1042:1047	lower levels	1036:1047	lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin	1036:1119	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	1	28	dep	serine	161:166	arg1	residues					182:189	residues	182:189	residues	182:189	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	1	29	theme	N-acetylglucosamine	226:244	arg1	residues					257:264	N-acetylglucosamine (O-GlcNAc) residues	226:264	N-acetylglucosamine (O-GlcNAc) residues	226:264	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	4	30	theme	convergent	596:605	arg1	pathway					617:623	a convergent metabolic pathway	594:623	a convergent metabolic pathway	594:623	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29756380	6	31	theme	Decreased	943:951	arg1	O-GlcNAc					953:960	Decreased O-GlcNAc	943:960	Decreased O-GlcNAc	943:960	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	6	32	theme	decreased	1152:1160	arg1	levels					1171:1176	decreased O-GlcNAc levels	1152:1176	decreased O-GlcNAc levels	1152:1176	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	1	33	theme	serine	161:166	arg1	glycosylation					144:156	O-Linked glycosylation	135:156	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues	135:264	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	3	34	theme	metabolic	429:437	arg1	inhibitors					449:458	metabolic precursor inhibitors	429:458	metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice	429:516	Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice.
29756380	6	35	theme	leptin	1114:1119	arg1	levels					1042:1047	lower levels	1036:1047	lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin	1036:1119	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	0	36	theme	Transferase	33:43	arg1	Inhibitors					10:19	Metabolic Inhibitors	0:19	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo	0:60	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.
29756380	1	37	gly	glycosylation	144:156	arg1	threonine					172:180	threonine	172:180	threonine	172:180	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	1	37	gly	glycosylation	144:156	arg1	serine					161:166	serine	161:166	serine	161:166	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	6	38	theme	transcription	1056:1068	arg1	Sp1					1077:1079	the transcription factor Sp1	1052:1079	the transcription factor Sp1	1052:1079	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	5	39	theme	time-dependent	879:892	arg1	decreases					894:902	dose- and time-dependent decreases	869:902	dose- and time-dependent decreases in O-GlcNAc levels in various tissues	869:940	We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues.
29756380	5	40	from	levels	916:921	arg1	tissues					934:940	various tissues	926:940	various tissues	926:940	We show that of these inhibitors, 2-deoxy-2-N-hexanamide-5-thio-d-glucopyranoside (5SGlcNHex) acts in vivo to induce dose- and time-dependent decreases in O-GlcNAc levels in various tissues.
29756380	6	41	theme	hormone	1106:1112	arg1	leptin					1114:1119	the satiety-inducing hormone leptin	1085:1119	the satiety-inducing hormone leptin	1085:1119	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	6	42	theme	peripheral	1202:1211	arg1	tissues					1213:1219	peripheral tissues	1202:1219	peripheral tissues of mammals	1202:1230	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	1	43	theme	O-Linked	135:142	arg1	glycosylation					144:156	O-Linked glycosylation	135:156	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues	135:264	O-Linked glycosylation of serine and threonine residues of nucleocytoplasmic proteins with N-acetylglucosamine (O-GlcNAc) residues is catalyzed by O-GlcNAc transferase (OGT).
29756380	4	44	theme	N-acetylglucosamine	550:568	arg1	analogues					537:545	These 5-thiosugar analogues	519:545	These 5-thiosugar analogues of N-acetylglucosamine	519:568	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29756380	6	45	theme	satiety-inducing	1089:1104	arg1	leptin					1114:1119	the satiety-inducing hormone leptin	1085:1119	the satiety-inducing hormone leptin	1085:1119	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	3	46	dep	use	480:482	arg1	both					484:487	both	484:487	both	484:487	Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice.
29756380	6	47	theme	nutrient	1182:1189	arg1	sensing					1191:1197	nutrient sensing	1182:1197	nutrient sensing in peripheral tissues of mammals	1182:1230	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	0	48	theme	Decreased	72:80	arg1	Levels					91:96	Decreased O-GlcNAc Levels	72:96	Decreased O-GlcNAc Levels	72:96	Metabolic Inhibitors of O-GlcNAc Transferase That Act In Vivo Implicate Decreased O-GlcNAc Levels in Leptin-Mediated Nutrient Sensing.
29756380	2	49	theme	physiological	384:396	arg1	processes					398:406	physiological processes	384:406	physiological processes	384:406	O-GlcNAc is conserved within mammals and is implicated in a wide range of physiological processes.
29756380	3	50	theme	suitable	467:474	arg1	inhibitors					449:458	metabolic precursor inhibitors	429:458	metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice	429:516	Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice.
29756380	3	51	theme	precursor	439:447	arg1	inhibitors					449:458	metabolic precursor inhibitors	429:458	metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice	429:516	Herein, we describe metabolic precursor inhibitors of OGT suitable for use both in cells and in vivo in mice.
29756380	6	52	theme	Sp1	1077:1079	arg1	levels					1042:1047	lower levels	1036:1047	lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin	1036:1119	Decreased O-GlcNAc correlates, both in vitro within adipocytes and in vivo within mice, with lower levels of the transcription factor Sp1 and the satiety-inducing hormone leptin, thus revealing a link between decreased O-GlcNAc levels and nutrient sensing in peripheral tissues of mammals.
29756380	4	53	theme	OGT	724:726	arg1	inhibitor					728:736	a common OGT inhibitor	715:736	a common OGT inhibitor	715:736	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29756380	4	54	theme	N-acetylglucosamine-6-phosphate	648:678	arg1	NAGA					696:699	NAGA	696:699	NAGA	696:699	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29756380	4	54	theme	N-acetylglucosamine-6-phosphate	648:678	arg1	de-N-acetylase					680:693	N-acetylglucosamine-6-phosphate de-N-acetylase	648:693	N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA)	648:700	These 5-thiosugar analogues of N-acetylglucosamine are assimilated through a convergent metabolic pathway, most likely involving N-acetylglucosamine-6-phosphate de-N-acetylase (NAGA), to generate a common OGT inhibitor within cells.
29590630	1	0	theme	selective	194:202	arg1	barrier					204:210	the selective barrier	190:210	the selective barrier of the nuclear pore complex (NPC)	190:244	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	4	1	theme	magnitude	765:773	arg1	order					756:760	an order	753:760	an order of magnitude	753:773	Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs.
29590630	6	2	theme	β-N-acetylglucosamine-modified	1027:1056	arg1	FG-Nups					1058:1064	O-linked β-N-acetylglucosamine-modified FG-Nups	1018:1064	O-linked β-N-acetylglucosamine-modified FG-Nups	1018:1064	The same distinct binding mechanisms are unperturbed in O-linked β-N-acetylglucosamine-modified FG-Nups.
29590630	6	3	theme	O-linked	1018:1025	arg1	FG-Nups					1058:1064	O-linked β-N-acetylglucosamine-modified FG-Nups	1018:1064	O-linked β-N-acetylglucosamine-modified FG-Nups	1018:1064	The same distinct binding mechanisms are unperturbed in O-linked β-N-acetylglucosamine-modified FG-Nups.
29590630	4	4	theme	archetypal-fuzzy	793:808	arg1	complex					810:816	the archetypal-fuzzy complex	789:816	the archetypal-fuzzy complex between FG-Nup153 and NTRs	789:843	Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs.
29590630	2	5	theme	rapid	400:404	arg1	formation					406:414	rapid formation	400:414	rapid formation	400:414	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	7	6	contain	have	1079:1082	arg2	implications					1084:1095	implications	1084:1095	implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell	1084:1190	Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
29590630	7	6	contain	have	1079:1082	arg1	results					1071:1077	Our results	1067:1077	Our results	1067:1077	Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
29590630	1	7	theme	Phenylalanine-glycine-rich	88:113	arg1	proteins					167:174	disordered proteins	156:174	disordered proteins	156:174	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	1	7	theme	Phenylalanine-glycine-rich	88:113	arg1	FG-Nups					129:135	FG-Nups	129:135	FG-Nups	129:135	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	1	7	theme	Phenylalanine-glycine-rich	88:113	arg1	nucleoporins					115:126	Phenylalanine-glycine-rich nucleoporins	88:126	Phenylalanine-glycine-rich nucleoporins (FG-Nups)	88:136	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	0	8	theme	Differential	4:15	arg1	Mechanisms					25:34	Two Differential Binding Mechanisms	0:34	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors	0:85	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.
29590630	7	9	theme	interactions	1167:1178	arg1	roles					1114:1118	differential roles	1101:1118	differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell	1101:1190	Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
29590630	3	10	theme	sharp	567:571	arg1	contrast					573:580	sharp contrast	567:580	sharp contrast	567:580	Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1.
29590630	2	11	theme	many	450:453	arg1	motifs					469:474	many individual FG motifs	450:474	many individual FG motifs	450:474	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	6	12	link	O-linked	1018:1025	arg1	FG-Nups					1058:1064	O-linked β-N-acetylglucosamine-modified FG-Nups	1018:1064	O-linked β-N-acetylglucosamine-modified FG-Nups	1018:1064	The same distinct binding mechanisms are unperturbed in O-linked β-N-acetylglucosamine-modified FG-Nups.
29590630	1	13	theme	nuclear	219:225	arg1	complex					232:238	the nuclear pore complex	215:238	the nuclear pore complex (NPC)	215:244	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	1	13	theme	nuclear	219:225	arg1	NPC					241:243	NPC	241:243	NPC	241:243	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	7	14	theme	distributed	1144:1154	arg1	interactions					1167:1178	distinctly spatially distributed FG-Nup⋅NTR interactions	1123:1178	distinctly spatially distributed FG-Nup⋅NTR interactions	1123:1178	Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
29590630	1	15	theme	pore	227:230	arg1	complex					232:238	the nuclear pore complex	215:238	the nuclear pore complex (NPC)	215:244	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	1	15	theme	pore	227:230	arg1	NPC					241:243	NPC	241:243	NPC	241:243	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	2	16	theme	interactions	432:443	arg1	breakage					420:427	breakage	420:427	breakage	420:427	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	2	16	theme	interactions	432:443	arg1	formation					406:414	rapid formation	400:414	rapid formation	400:414	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	7	17	theme	FG-Nup⋅NTR	1156:1165	arg1	interactions					1167:1178	distinctly spatially distributed FG-Nup⋅NTR interactions	1123:1178	distinctly spatially distributed FG-Nup⋅NTR interactions	1123:1178	Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
29590630	4	18	theme	rate	724:727	arg1	constants					729:737	dissociation rate constants	711:737	dissociation rate constants	711:737	Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs.
29590630	1	19	theme	complex	232:238	arg1	barrier					204:210	the selective barrier	190:210	the selective barrier of the nuclear pore complex (NPC)	190:244	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	0	20	theme	FG-Nucleoporins	39:53	arg1	Mechanisms					25:34	Two Differential Binding Mechanisms	0:34	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors	0:85	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.
29590630	2	21	theme	individual	455:464	arg1	motifs					469:474	many individual FG motifs	450:474	many individual FG motifs	450:474	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	3	22	theme	export	673:678	arg1	CRM1					689:692	the export receptor CRM1	669:692	the export receptor CRM1	669:692	Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1.
29590630	4	23	theme	dissociation	711:722	arg1	constants					729:737	dissociation rate constants	711:737	dissociation rate constants	711:737	Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs.
29590630	6	24	theme	binding	980:986	arg1	mechanisms					988:997	The same distinct binding mechanisms	962:997	The same distinct binding mechanisms	962:997	The same distinct binding mechanisms are unperturbed in O-linked β-N-acetylglucosamine-modified FG-Nups.
29590630	2	25	theme	Previous	247:254	arg1	studies					256:262	Previous studies	247:262	Previous studies	247:262	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	0	26	theme	Nuclear	59:65	arg1	Receptors					77:85	Nuclear Transport Receptors	59:85	Nuclear Transport Receptors	59:85	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.
29590630	6	27	theme	same distinct	966:978	arg1	mechanisms					988:997	The same distinct binding mechanisms	962:997	The same distinct binding mechanisms	962:997	The same distinct binding mechanisms are unperturbed in O-linked β-N-acetylglucosamine-modified FG-Nups.
29590630	2	28	with	interactions	432:443	arg1	motifs					469:474	many individual FG motifs	450:474	many individual FG motifs	450:474	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	2	29	theme	FG	466:467	arg1	motifs					469:474	many individual FG motifs	450:474	many individual FG motifs	450:474	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	3	30	theme	single-molecule	490:504	arg1	studies					506:512	single-molecule studies	490:512	single-molecule studies combined with atomistic simulations	490:548	Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1.
29590630	3	31	theme	reconfiguration-binding	613:635	arg1	mechanism					637:645	a coupled reconfiguration-binding mechanism	603:645	a coupled reconfiguration-binding mechanism	603:645	Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1.
29590630	2	32	theme	transport	284:292	arg1	NTRs					305:308	NTRs	305:308	NTRs	305:308	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	2	32	theme	transport	284:292	arg1	receptors					294:302	nuclear transport receptors	276:302	nuclear transport receptors (NTRs)	276:309	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	2	33	dep	formation	406:414	arg1	the					396:398	the	396:398	the	396:398	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	1	34	theme	disordered	156:165	arg1	proteins					167:174	disordered proteins	156:174	disordered proteins	156:174	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	1	34	theme	disordered	156:165	arg1	nucleoporins					115:126	Phenylalanine-glycine-rich nucleoporins	88:126	Phenylalanine-glycine-rich nucleoporins (FG-Nups)	88:136	Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC).
29590630	7	35	theme	differential	1101:1112	arg1	roles					1114:1118	differential roles	1101:1118	differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell	1101:1190	Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
29590630	3	36	theme	receptor	680:687	arg1	CRM1					689:692	the export receptor CRM1	669:692	the export receptor CRM1	669:692	Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1.
29590630	2	37	theme	nuclear	276:282	arg1	NTRs					305:308	NTRs	305:308	NTRs	305:308	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	2	37	theme	nuclear	276:282	arg1	receptors					294:302	nuclear transport receptors	276:302	nuclear transport receptors (NTRs)	276:309	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	3	38	theme	atomistic	528:536	arg1	simulations					538:548	atomistic simulations	528:548	atomistic simulations	528:548	Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1.
29590630	5	39	theme	FG-Nup214	942:950	arg1	sequence					952:959	the FG-Nup214 sequence	938:959	the FG-Nup214 sequence	938:959	Unexpectedly, this behavior appears not to be encoded selectively into CRM1 but rather into the FG-Nup214 sequence.
29590630	0	40	theme	Receptors	77:85	arg1	Mechanisms					25:34	Two Differential Binding Mechanisms	0:34	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors	0:85	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.
29590630	3	41	theme	coupled	605:611	arg1	mechanism					637:645	a coupled reconfiguration-binding mechanism	603:645	a coupled reconfiguration-binding mechanism	603:645	Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1.
29590630	2	42	theme	"	378:378	arg1	complex					380:386	an "archetypal-fuzzy" complex	358:386	an "archetypal-fuzzy" complex	358:386	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29590630	7	43	from	roles	1114:1118	arg1	cell					1187:1190	the cell	1183:1190	the cell	1183:1190	Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell.
29590630	0	44	theme	Transport	67:75	arg1	Receptors					77:85	Nuclear Transport Receptors	59:85	Nuclear Transport Receptors	59:85	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.
29590630	0	45	theme	Binding	17:23	arg1	Mechanisms					25:34	Two Differential Binding Mechanisms	0:34	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors	0:85	Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors.
29590630	2	46	theme	archetypal-fuzzy	362:377	arg1	complex					380:386	an "archetypal-fuzzy" complex	358:386	an "archetypal-fuzzy" complex	358:386	Previous studies showed that nuclear transport receptors (NTRs) were found to interact with FG-Nups by forming an "archetypal-fuzzy" complex through the rapid formation and breakage of interactions with many individual FG motifs.
29577901	1	0	theme	receptor	123:130	arg1	superfamily					132:142	the nuclear receptor superfamily	111:142	the nuclear receptor superfamily	111:142	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	8	1	dep	sites	1318:1322	arg1	S391					1351:1354	S391	1351:1354	S391	1351:1354	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	1	dep	sites	1318:1322	arg1	S437					1372:1375	S437	1372:1375	S437	1372:1375	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	1	dep	sites	1318:1322	arg1	sites					1318:1322	four new O-GlcNAc sites	1300:1322	four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437	1300:1375	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	1	dep	sites	1318:1322	arg1	S399					1363:1366	S399	1363:1366	S399	1363:1366	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	1	dep	sites	1318:1322	arg1	T393					1357:1360	T393	1357:1360	T393	1357:1360	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	4	2	from	modified	574:581	arg1	NTD					609:611	NTD	609:611	NTD	609:611	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	4	2	from	modified	574:581	arg1	domain					601:606	its N-terminal domain	586:606	its N-terminal domain (NTD)	586:612	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	2	3	link	O-linked	327:334	arg1	O-GlcNAc					360:367	O-GlcNAc	360:367	O-GlcNAc	360:367	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	2	3	link	O-linked	327:334	arg1	β-N-acetyl-glucosamine					336:357	O-linked β-N-acetyl-glucosamine	327:357	O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity	327:408	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	7	4	from	peptide	1195:1201	arg1	ncOGT					1073:1077	ncOGT	1073:1077	ncOGT	1073:1077	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	4	from	peptide	1195:1201	arg1	isoform					1064:1070	the longest OGT isoform	1048:1070	the longest OGT isoform (ncOGT)	1048:1078	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	4	from	peptide	1195:1201	arg1	Int-D					1252:1256	Int-D	1252:1256	Int-D	1252:1256	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	4	from	peptide	1195:1201	arg1	region					1244:1249	the intervening region	1228:1249	the intervening region (Int-D) within the catalytic domain	1228:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	5	theme	O-GlcNAc	1177:1184	arg1	peptide					1195:1201	a new O-GlcNAc modified peptide	1171:1201	a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain	1171:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	5	theme	O-GlcNAc	1177:1184	arg1	acids					1210:1214	amino acids 826-832	1204:1222	amino acids 826-832	1204:1222	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	4	6	theme	human	551:555	arg1	LXRα					557:560	human LXRα	551:560	human LXRα	551:560	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	1	7	theme	inflammatory	232:243	arg1	responses					245:253	inflammatory responses	232:253	inflammatory responses	232:253	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	7	8	theme	far	1151:1153	arg1	C-terminus					1155:1164	the far C-terminus	1147:1164	the far C-terminus	1147:1164	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	9	theme	new	1173:1175	arg1	peptide					1195:1201	a new O-GlcNAc modified peptide	1171:1201	a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain	1171:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	9	theme	new	1173:1175	arg1	acids					1210:1214	amino acids 826-832	1204:1222	amino acids 826-832	1204:1222	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	8	10	from	sites	1318:1322	arg1	sOGT					1345:1348	the short isoform sOGT	1327:1348	the short isoform sOGT	1327:1348	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	7	11	theme	amino	1204:1208	arg1	peptide					1195:1201	a new O-GlcNAc modified peptide	1171:1201	a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain	1171:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	11	theme	amino	1204:1208	arg1	acids					1210:1214	amino acids 826-832	1204:1222	amino acids 826-832	1204:1222	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	4	12	theme	novel	664:668	arg1	20LWKPGAQDASSQAQGGSSCILRE42					696:722	a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42	662:722	a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42	662:722	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	7	13	theme	intervening	1232:1242	arg1	Int-D					1252:1256	Int-D	1252:1256	Int-D	1252:1256	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	13	theme	intervening	1232:1242	arg1	region					1244:1249	the intervening region	1228:1249	the intervening region (Int-D) within the catalytic domain	1228:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	4	14	theme	specific	631:638	arg1	S49					654:656	a specific O-GlcNAc site S49	629:656	a specific O-GlcNAc site S49	629:656	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	7	15	from	S437	1081:1084	arg1	domain					1127:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	15	from	S437	1081:1084	arg1	C-terminus					1155:1164	the far C-terminus	1147:1164	the far C-terminus	1147:1164	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	1	16	theme	Liver	74:78	arg1	Receptor					82:89	The Liver X Receptor α	70:91	The Liver X Receptor α (LXRα)	70:98	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	1	16	theme	Liver	74:78	arg1	LXRα					94:97	LXRα	94:97	LXRα	94:97	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	2	17	theme	transcriptional	385:399	arg1	activity					401:408	increased transcriptional activity	375:408	increased transcriptional activity	375:408	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	1	18	theme	X	80:80	arg1	Receptor					82:89	The Liver X Receptor α	70:91	The Liver X Receptor α (LXRα)	70:98	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	1	18	theme	X	80:80	arg1	LXRα					94:97	LXRα	94:97	LXRα	94:97	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	2	19	theme	increased	375:383	arg1	activity					401:408	increased transcriptional activity	375:408	increased transcriptional activity	375:408	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	0	20	theme	O-GlcNAc	0:7	arg1	site-mapping					9:20	O-GlcNAc site-mapping	0:20	O-GlcNAc site-mapping of liver X receptor-α	0:42	O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.
29577901	4	21	theme	peptide	688:694	arg1	20LWKPGAQDASSQAQGGSSCILRE42					696:722	a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42	662:722	a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42	662:722	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	1	22	theme	essential	157:165	arg1	role					167:170	an essential role	154:170	an essential role	154:170	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	0	23	theme	liver	25:29	arg1	transferase					57:67	O-GlcNAc transferase	48:67	O-GlcNAc transferase	48:67	O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.
29577901	0	23	theme	liver	25:29	arg1	site-mapping					9:20	O-GlcNAc site-mapping	0:20	O-GlcNAc site-mapping of liver X receptor-α	0:42	O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.
29577901	5	24	theme	selected	799:806	arg1	promoters					820:828	selected target gene promoters	799:828	selected target gene promoters	799:828	However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro.
29577901	7	25	theme	longest	1052:1058	arg1	ncOGT					1073:1077	ncOGT	1073:1077	ncOGT	1073:1077	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	25	theme	longest	1052:1058	arg1	isoform					1064:1070	the longest OGT isoform	1048:1070	the longest OGT isoform (ncOGT)	1048:1078	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	26	theme	modified	1186:1193	arg1	peptide					1195:1201	a new O-GlcNAc modified peptide	1171:1201	a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain	1171:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	26	theme	modified	1186:1193	arg1	acids					1210:1214	amino acids 826-832	1204:1222	amino acids 826-832	1204:1222	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	5	27	theme	LXRα	775:778	arg1	transactivation					780:794	LXRα transactivation	775:794	LXRα transactivation of selected target gene promoters	775:828	However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro.
29577901	9	28	theme	O-GlcNAc	1464:1471	arg1	sites					1473:1477	identified O-GlcNAc sites	1453:1477	identified O-GlcNAc sites	1453:1477	Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
29577901	3	29	theme	transferase	466:476	arg1	in vitro					484:491	O-GlcNAc transferase (OGT) in vitro	457:491	O-GlcNAc transferase (OGT) in vitro	457:491	Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver.
29577901	5	30	theme	gene	815:818	arg1	promoters					820:828	selected target gene promoters	799:828	selected target gene promoters	799:828	However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro.
29577901	7	31	theme	OGT	1060:1062	arg1	ncOGT					1073:1077	ncOGT	1073:1077	ncOGT	1073:1077	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	31	theme	OGT	1060:1062	arg1	isoform					1064:1070	the longest OGT isoform	1048:1070	the longest OGT isoform (ncOGT)	1048:1078	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	9	32	theme	identified	1453:1462	arg1	sites					1473:1477	identified O-GlcNAc sites	1453:1477	identified O-GlcNAc sites	1453:1477	Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
29577901	9	33	theme	Future	1403:1408	arg1	studies					1410:1416	Future studies	1403:1416	Future studies	1403:1416	Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
29577901	4	34	theme	site	649:652	arg1	S49					654:656	a specific O-GlcNAc site S49	629:656	a specific O-GlcNAc site S49	629:656	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	0	35	theme	receptor-α	33:42	arg1	transferase					57:67	O-GlcNAc transferase	48:67	O-GlcNAc transferase	48:67	O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.
29577901	0	35	theme	receptor-α	33:42	arg1	site-mapping					9:20	O-GlcNAc site-mapping	0:20	O-GlcNAc site-mapping of liver X receptor-α	0:42	O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.
29577901	9	36	theme	biological	1434:1443	arg1	role					1445:1448	the biological role	1430:1448	the biological role of identified O-GlcNAc sites in LXRα and OGT	1430:1493	Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
29577901	6	37	theme	co-immunoprecipitation	858:879	arg1	assays					881:886	Peptide array and co-immunoprecipitation assays	840:886	assays	881:886	Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion.
29577901	8	38	theme	new	1305:1307	arg1	S391					1351:1354	S391	1351:1354	S391	1351:1354	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	38	theme	new	1305:1307	arg1	S437					1372:1375	S437	1372:1375	S437	1372:1375	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	38	theme	new	1305:1307	arg1	sites					1318:1322	four new O-GlcNAc sites	1300:1322	four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437	1300:1375	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	38	theme	new	1305:1307	arg1	S399					1363:1366	S399	1363:1366	S399	1363:1366	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	38	theme	new	1305:1307	arg1	T393					1357:1360	T393	1357:1360	T393	1357:1360	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	4	39	from	domain	601:606	arg1	modified					574:581	modified	574:581	modified	574:581	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	7	40	theme	tetratricopeptide	1093:1109	arg1	domain					1127:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	41	theme	TPR	1119:1121	arg1	domain					1127:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	5	42	theme	target	808:813	arg1	promoters					820:828	selected target gene promoters	799:828	selected target gene promoters	799:828	However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro.
29577901	3	43	theme	O-GlcNAc	457:464	arg1	OGT					479:481	OGT	479:481	OGT	479:481	Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver.
29577901	3	43	theme	O-GlcNAc	457:464	arg1	transferase					466:476	O-GlcNAc transferase	457:476	O-GlcNAc transferase (OGT) in vitro	457:491	Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver.
29577901	0	44	theme	O-GlcNAc	48:55	arg1	transferase					57:67	O-GlcNAc transferase	48:67	O-GlcNAc transferase	48:67	O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.
29577901	6	45	theme	ligand-binding	944:957	arg1	LBD					967:969	LBD	967:969	LBD	967:969	Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion.
29577901	6	45	theme	ligand-binding	944:957	arg1	domain					959:964	ligand-binding domain	944:964	ligand-binding domain (LBD)	944:970	Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion.
29577901	7	46	theme	O-GlcNAc	1030:1037	arg1	sites					1039:1043	two new O-GlcNAc sites	1022:1043	two new O-GlcNAc sites in the longest OGT isoform (ncOGT)	1022:1078	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	2	47	theme	O-linked	327:334	arg1	O-GlcNAc					360:367	O-GlcNAc	360:367	O-GlcNAc	360:367	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	2	47	theme	O-linked	327:334	arg1	β-N-acetyl-glucosamine					336:357	O-linked β-N-acetyl-glucosamine	327:357	O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity	327:408	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	7	48	theme	repeat	1111:1116	arg1	domain					1127:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	the tetratricopeptide repeat (TPR) 13 domain	1089:1132	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	6	49	theme	Peptide	840:846	arg1	array					848:852	Peptide array and co-immunoprecipitation assays	840:886	array	848:852	Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion.
29577901	8	50	theme	O-GlcNAc	1309:1316	arg1	S391					1351:1354	S391	1351:1354	S391	1351:1354	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	50	theme	O-GlcNAc	1309:1316	arg1	S437					1372:1375	S437	1372:1375	S437	1372:1375	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	50	theme	O-GlcNAc	1309:1316	arg1	sites					1318:1322	four new O-GlcNAc sites	1300:1322	four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437	1300:1375	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	50	theme	O-GlcNAc	1309:1316	arg1	S399					1363:1366	S399	1363:1366	S399	1363:1366	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	50	theme	O-GlcNAc	1309:1316	arg1	T393					1357:1360	T393	1357:1360	T393	1357:1360	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	8	51	theme	short	1331:1335	arg1	isoform					1337:1343	the short isoform	1327:1343	the short isoform sOGT	1327:1348	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	6	52	from	domain	959:964	arg1	NTD					936:938	its NTD	932:938	its NTD	932:938	Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion.
29577901	2	53	with	β-N-acetyl-glucosamine	336:357	arg1	activity					401:408	increased transcriptional activity	375:408	increased transcriptional activity	375:408	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	7	54	theme	catalytic	1270:1278	arg1	domain					1280:1285	the catalytic domain	1266:1285	the catalytic domain	1266:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	9	55	theme	sites	1473:1477	arg1	role					1445:1448	the biological role	1430:1448	the biological role of identified O-GlcNAc sites in LXRα and OGT	1430:1493	Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
29577901	4	56	theme	modified	679:686	arg1	20LWKPGAQDASSQAQGGSSCILRE42					696:722	a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42	662:722	a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42	662:722	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	2	57	mod	modified	315:322	arg3	β-N-acetyl-glucosamine					336:357	O-linked β-N-acetyl-glucosamine	327:357	O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity	327:408	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	2	57	mod	modified	315:322	arg1	LXRα					286:289	LXRα	286:289	LXRα	286:289	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	2	57	mod	modified	315:322	arg3	O-GlcNAc					360:367	O-GlcNAc	360:367	O-GlcNAc	360:367	We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity.
29577901	6	58	theme	ligand-independent	977:994	arg1	fashion					996:1002	a ligand-independent fashion	975:1002	a ligand-independent fashion	975:1002	Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion.
29577901	7	59	theme	new	1026:1028	arg1	sites					1039:1043	two new O-GlcNAc sites	1022:1043	two new O-GlcNAc sites in the longest OGT isoform (ncOGT)	1022:1078	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	4	60	theme	O-GlcNAc	640:647	arg1	S49					654:656	a specific O-GlcNAc site S49	629:656	a specific O-GlcNAc site S49	629:656	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	1	61	theme	lipid	199:203	arg1	metabolism					217:226	cholesterol, lipid and glucose metabolism	186:226	metabolism	217:226	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	6	62	from	OGT	925:927	arg1	NTD					936:938	its NTD	932:938	its NTD	932:938	Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion.
29577901	1	63	theme	cholesterol	186:196	arg1	metabolism					217:226	cholesterol, lipid and glucose metabolism	186:226	metabolism	217:226	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	8	64	theme	isoform	1337:1343	arg1	sOGT					1345:1348	the short isoform sOGT	1327:1348	the short isoform sOGT	1327:1348	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	5	65	theme	promoters	820:828	arg1	transactivation					780:794	LXRα transactivation	775:794	LXRα transactivation of selected target gene promoters	775:828	However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro.
29577901	3	66	theme	mouse	508:512	arg1	liver					514:518	mouse liver	508:518	mouse liver	508:518	Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver.
29577901	9	67	from	role	1445:1448	arg1	OGT					1491:1493	OGT	1491:1493	OGT	1491:1493	Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
29577901	9	67	from	role	1445:1448	arg1	LXRα					1482:1485	LXRα	1482:1485	LXRα	1482:1485	Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT.
29577901	4	68	theme	N-terminal	590:599	arg1	NTD					609:611	NTD	609:611	NTD	609:611	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	4	68	theme	N-terminal	590:599	arg1	domain					601:606	its N-terminal domain	586:606	its N-terminal domain (NTD)	586:612	In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20LWKPGAQDASSQAQGGSSCILRE42.
29577901	5	69	theme	O-GlcNAc	734:741	arg1	site-mutations					743:756	O-GlcNAc site-mutations	734:756	O-GlcNAc site-mutations	734:756	However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro.
29577901	7	70	from	sites	1039:1043	arg1	ncOGT					1073:1077	ncOGT	1073:1077	ncOGT	1073:1077	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	70	from	sites	1039:1043	arg1	isoform					1064:1070	the longest OGT isoform	1048:1070	the longest OGT isoform (ncOGT)	1048:1078	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	70	from	sites	1039:1043	arg1	Int-D					1252:1256	Int-D	1252:1256	Int-D	1252:1256	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	7	70	from	sites	1039:1043	arg1	region					1244:1249	the intervening region	1228:1249	the intervening region (Int-D) within the catalytic domain	1228:1285	Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain.
29577901	1	71	theme	nuclear	115:121	arg1	superfamily					132:142	the nuclear receptor superfamily	111:142	the nuclear receptor superfamily	111:142	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29577901	8	72	theme	TPRs	1384:1387	arg1	domain					1395:1400	the TPRs 11-13 domain	1380:1400	the TPRs 11-13 domain	1380:1400	We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain.
29577901	1	73	theme	glucose	209:215	arg1	metabolism					217:226	cholesterol, lipid and glucose metabolism	186:226	metabolism	217:226	The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses.
29504744	3	0	theme	mW	740:741	arg1	engraver					758:765	a 1000 mW benchtop laser engraver	733:765	a 1000 mW benchtop laser engraver	733:765	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	4	1	theme	surface	930:936	arg1	area					938:941	surface area	930:941	surface area	930:941	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	6	2	theme	model	1235:1239	arg1	OP					1241:1242	a model OP	1233:1242	a model OP	1233:1242	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	2	theme	model	1235:1239	arg1	paraoxon					1223:1230	the insecticide paraoxon	1207:1230	(5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM)	1187:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	3	3	theme	deposited	789:797	arg1	nanoparticles					808:820	electrochemically deposited platinum nanoparticles	771:820	electrochemically deposited platinum nanoparticles (dia	771:825	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	7	4	theme	sensing	1465:1471	arg1	event					1473:1477	sensing event	1465:1477	sensing event	1465:1477	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	8	5	theme	in-field	1809:1816	arg1	applications					1818:1829	in-field applications	1809:1829	in-field applications	1809:1829	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	6	6	theme	insecticide	1211:1221	arg1	OP					1241:1242	a model OP	1233:1242	a model OP	1233:1242	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	6	theme	insecticide	1211:1221	arg1	time					1201:1204	5 s response time	1188:1204	5 s response time	1188:1204	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	6	theme	insecticide	1211:1221	arg1	paraoxon					1223:1230	the insecticide paraoxon	1207:1230	(5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM)	1187:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	1	7	theme	attractive	217:226	arg1	technique					261:269	an attractive low-cost, scalable manufacturing technique	214:269	an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors	214:315	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	6	8	with	paraoxon	1223:1230	arg1	limit					1266:1270	a low detection limit	1250:1270	a low detection limit (3 nM)	1250:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	8	with	paraoxon	1223:1230	arg1	nM					1275:1276	3 nM	1273:1276	3 nM	1273:1276	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	2	9	theme	acute	599:603	arg1	toxicity					605:612	acute toxicity	599:612	acute toxicity as well as long-term pollution to soils and waterways	599:666	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	7	10	theme	high	1403:1406	arg1	reusability					1408:1418	high reusability	1403:1418	high reusability (average of 0.3% decrease in sensitivity per sensing event)	1403:1478	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	7	11	dep	longevity	1542:1550	arg1	%					1555:1555	70%	1553:1555	70% retained sensitivity after 8 weeks	1553:1590	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	2	12	theme	graphene-based	336:349	arg1	electrode					351:359	a graphene-based electrode	334:359	a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs)	334:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	4	13	theme	enzyme	984:989	arg1	functionalization					991:1007	subsequent enzyme functionalization	973:1007	subsequent enzyme functionalization	973:1007	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	6	14	theme	negligible	1318:1327	arg1	interference					1329:1340	negligible interference	1318:1340	negligible interference from similar nerve agents	1318:1366	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	1	15	theme	manufacturing	247:259	arg1	technique					261:269	an attractive low-cost, scalable manufacturing technique	214:269	an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors	214:315	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	6	16	theme	detection	1256:1264	arg1	limit					1266:1270	a low detection limit	1250:1270	a low detection limit (3 nM)	1250:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	16	theme	detection	1256:1264	arg1	nM					1275:1276	3 nM	1273:1276	3 nM	1273:1276	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	8	17	theme	scalable	1696:1703	arg1	technique					1736:1744	a scalable printed graphene manufacturing technique	1694:1744	a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1694:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	1	18	theme	Solution	141:148	arg1	printing					156:163	Solution phase printing	141:163	Solution phase printing of graphene-based electrodes	141:192	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	4	19	theme	electroactive	948:960	arg1	nature					962:967	electroactive nature	948:967	electroactive nature	948:967	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	7	20	from	sense	1625:1629	arg1	samples					1659:1665	actual soil and water samples	1637:1665	actual soil and water samples	1637:1665	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	8	21	theme	low-cost	1863:1870	arg1	strips					1887:1892	low-cost biosensor test strips	1863:1892	low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1863:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	7	22	theme	%	1435:1435	arg1	decrease					1437:1444	0.3% decrease	1432:1444	0.3% decrease in sensitivity	1432:1459	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	8	23	theme	graphene	1713:1720	arg1	technique					1736:1744	a scalable printed graphene manufacturing technique	1694:1744	a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1694:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	8	24	theme	test	1882:1885	arg1	strips					1887:1892	low-cost biosensor test strips	1863:1892	low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1863:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	3	25	dep	nanoparticles	808:820	arg1	dia					823:825	dia	823:825	dia	823:825	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	8	26	theme	sensing	1949:1955	arg1	paradigms					1957:1965	wearable or disposable sensing paradigms	1926:1965	wearable or disposable sensing paradigms	1926:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	7	27	dep	reusability	1408:1418	arg1	average					1421:1427	average	1421:1427	average of 0.3% decrease in sensitivity per sensing event	1421:1477	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	7	28	theme	water	1653:1657	arg1	samples					1659:1665	actual soil and water samples	1637:1665	actual soil and water samples	1637:1665	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	0	29	theme	Rapid	90:94	arg1	Detection					110:118	Rapid and Sensitive Detection	90:118	Rapid and Sensitive Detection of Organophosphates	90:138	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	7	30	theme	soil	1644:1647	arg1	samples					1659:1665	actual soil and water samples	1637:1665	actual soil and water samples	1637:1665	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	0	31	theme	Sensitive	100:108	arg1	Detection					110:118	Rapid and Sensitive Detection	90:118	Rapid and Sensitive Detection of Organophosphates	90:138	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	6	32	from	agents	1361:1366	arg1	interference					1329:1340	negligible interference	1318:1340	negligible interference from similar nerve agents	1318:1366	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	5	33	theme	enzyme	1029:1034	arg1	PTE					1056:1058	PTE	1056:1058	PTE	1056:1058	The enzyme phosphotriesterase (PTE) was conjugated to the electrode surface via glutaraldehyde cross-linking.
29504744	5	33	theme	enzyme	1029:1034	arg1	phosphotriesterase					1036:1053	The enzyme phosphotriesterase	1025:1053	The enzyme phosphotriesterase (PTE)	1025:1059	The enzyme phosphotriesterase (PTE) was conjugated to the electrode surface via glutaraldehyde cross-linking.
29504744	2	34	theme	warfare	556:562	arg1	agents					564:569	chemical warfare agents	547:569	chemical warfare agents	547:569	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	8	35	used	used	1758:1761	arg2	technique					1736:1744	a scalable printed graphene manufacturing technique	1694:1744	a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1694:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	8	36	theme	wearable	1926:1933	arg1	paradigms					1957:1965	wearable or disposable sensing paradigms	1926:1965	wearable or disposable sensing paradigms	1926:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	6	37	theme	nerve	1355:1359	arg1	agents					1361:1366	similar nerve agents	1347:1366	similar nerve agents	1347:1366	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	0	38	theme	Printed	0:6	arg1	Biosensors					33:42	Printed Graphene Electrochemical Biosensors	0:42	Printed Graphene Electrochemical Biosensors	0:42	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	2	39	theme	phosphonate	464:474	arg1	OPs					494:496	OPs	494:496	OPs	494:496	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	39	theme	phosphonate	464:474	arg1	organophosphates					476:491	triple-O linked phosphonate organophosphates	448:491	triple-O linked phosphonate organophosphates (OPs)	448:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	0	40	theme	Electrochemical	17:31	arg1	Biosensors					33:42	Printed Graphene Electrochemical Biosensors	0:42	Printed Graphene Electrochemical Biosensors	0:42	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	4	41	theme	sheet	876:880	arg1	resistance					882:891	sheet resistance	876:891	sheet resistance decreased from ∼10 000 to 100 Ω/sq	876:926	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	2	42	theme	triple-O	448:455	arg1	OPs					494:496	OPs	494:496	OPs	494:496	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	42	theme	triple-O	448:455	arg1	organophosphates					476:491	triple-O linked phosphonate organophosphates	448:491	triple-O linked phosphonate organophosphates (OPs)	448:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	7	43	theme	current	1503:1509	arg1	retention					1518:1526	anodic current signal retention	1496:1526	90% anodic current signal retention	1492:1526	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	3	44	theme	graphene	685:692	arg1	electrode					694:702	The IML-printed graphene electrode	669:702	The IML-printed graphene electrode	669:702	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	0	45	theme	Inkjet	58:63	arg1	Lithography					74:84	Inkjet Maskless Lithography	58:84	Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates	58:138	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	6	46	theme	s	1190:1190	arg1	time					1201:1204	5 s response time	1188:1204	5 s response time	1188:1204	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	46	theme	s	1190:1190	arg1	paraoxon					1223:1230	the insecticide paraoxon	1207:1230	(5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM)	1187:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	2	47	theme	maskless	382:389	arg1	lithography					391:401	inkjet maskless lithography	375:401	inkjet maskless lithography (IML)	375:407	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	47	theme	maskless	382:389	arg1	IML					404:406	IML	404:406	IML	404:406	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	48	located	found	538:542	arg1	pesticides					575:584	pesticides	575:584	pesticides	575:584	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	48	located	found	538:542	arg1	agents					564:569	chemical warfare agents	547:569	chemical warfare agents	547:569	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	48	located	found	538:542	arg2	compounds					528:536	the active compounds	517:536	the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways	517:666	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	1	49	theme	graphene-based	168:181	arg1	electrodes					183:192	graphene-based electrodes	168:192	graphene-based electrodes	168:192	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	2	50	link	linked	457:462	arg1	OPs					494:496	OPs	494:496	OPs	494:496	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	50	link	linked	457:462	arg1	organophosphates					476:491	triple-O linked phosphonate organophosphates	448:491	triple-O linked phosphonate organophosphates (OPs)	448:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	1	51	dep	low-cost	228:235	arg1	scalable					238:245	scalable	238:245	scalable	238:245	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	6	52	with	sensitivity	1289:1299	arg1	limit					1266:1270	a low detection limit	1250:1270	a low detection limit (3 nM)	1250:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	52	with	sensitivity	1289:1299	arg1	nM					1275:1276	3 nM	1273:1276	3 nM	1273:1276	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	1	53	theme	electrochemical	290:304	arg1	biosensors					306:315	in-field electrochemical biosensors	281:315	in-field electrochemical biosensors	281:315	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	3	54	theme	benchtop	743:750	arg1	engraver					758:765	a 1000 mW benchtop laser engraver	733:765	a 1000 mW benchtop laser engraver	733:765	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	6	55	theme	high	1284:1287	arg1	sensitivity					1289:1299	high sensitivity	1284:1299	high sensitivity (370 nA/μM)	1284:1311	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	55	theme	high	1284:1287	arg1	nA/μM					1306:1310	370 nA/μM	1302:1310	370 nA/μM	1302:1310	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	7	56	dep	%	1494:1494	arg1	retention					1518:1526	anodic current signal retention	1496:1526	90% anodic current signal retention	1492:1526	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	2	57	theme	long-term	625:633	arg1	pollution					635:643	long-term pollution	625:643	acute toxicity as well as long-term pollution to soils and waterways	599:666	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	7	58	theme	decrease	1437:1444	arg1	average					1421:1427	average	1421:1427	average of 0.3% decrease in sensitivity per sensing event	1421:1477	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	3	59	theme	platinum	799:806	arg1	nanoparticles					808:820	electrochemically deposited platinum nanoparticles	771:820	electrochemically deposited platinum nanoparticles (dia	771:825	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	4	60	dep	conductivity	862:873	arg1	resistance					882:891	sheet resistance	876:891	sheet resistance decreased from ∼10 000 to 100 Ω/sq	876:926	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	7	61	theme	0.3	1432:1434	arg1	%					1435:1435	%	1435:1435	%	1435:1435	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	7	62	from	sensitivity	1449:1459	arg1	average					1421:1427	average	1421:1427	average of 0.3% decrease in sensitivity per sensing event	1421:1477	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	6	63	theme	similar	1347:1353	arg1	agents					1361:1366	similar nerve agents	1347:1366	similar nerve agents	1347:1366	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	1	64	theme	low-cost	228:235	arg1	technique					261:269	an attractive low-cost, scalable manufacturing technique	214:269	an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors	214:315	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	4	65	theme	subsequent	973:982	arg1	functionalization					991:1007	subsequent enzyme functionalization	973:1007	subsequent enzyme functionalization	973:1007	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	6	66	theme	low	1252:1254	arg1	limit					1266:1270	a low detection limit	1250:1270	a low detection limit (3 nM)	1250:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	66	theme	low	1252:1254	arg1	nM					1275:1276	3 nM	1273:1276	3 nM	1273:1276	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	8	67	theme	biosensor	1872:1880	arg1	strips					1887:1892	low-cost biosensor test strips	1863:1892	low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1863:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	5	68	theme	glutaraldehyde	1105:1118	arg1	cross-linking					1120:1132	glutaraldehyde cross-linking	1105:1132	glutaraldehyde cross-linking	1105:1132	The enzyme phosphotriesterase (PTE) was conjugated to the electrode surface via glutaraldehyde cross-linking.
29504744	1	69	theme	phase	150:154	arg1	printing					156:163	Solution phase printing	141:163	Solution phase printing of graphene-based electrodes	141:192	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	8	70	theme	disposable	1938:1947	arg1	paradigms					1957:1965	wearable or disposable sensing paradigms	1926:1965	wearable or disposable sensing paradigms	1926:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	8	71	theme	printed	1705:1711	arg1	technique					1736:1744	a scalable printed graphene manufacturing technique	1694:1744	a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1694:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	7	72	from	average	1421:1427	arg1	sensitivity					1449:1459	sensitivity	1449:1459	sensitivity	1449:1459	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	8	73	theme	manufacturing	1722:1734	arg1	technique					1736:1744	a scalable printed graphene manufacturing technique	1694:1744	a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1694:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	1	74	theme	electrodes	183:192	arg1	printing					156:163	Solution phase printing	141:163	Solution phase printing of graphene-based electrodes	141:192	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
29504744	2	75	theme	active	521:526	arg1	compounds					528:536	the active compounds	517:536	the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways	517:666	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	7	76	from	decrease	1437:1444	arg1	sensitivity					1449:1459	sensitivity	1449:1459	sensitivity	1449:1459	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	4	77	theme	∼25	828:830	arg1	nm					832:833	∼25 nm)	828:834	∼25 nm)	828:834	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	0	78	theme	Organophosphates	123:138	arg1	Detection					110:118	Rapid and Sensitive Detection	90:118	Rapid and Sensitive Detection of Organophosphates	90:138	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	7	79	theme	actual	1637:1642	arg1	samples					1659:1665	actual soil and water samples	1637:1665	actual soil and water samples	1637:1665	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	2	80	theme	chemical	547:554	arg1	agents					564:569	chemical warfare agents	547:569	chemical warfare agents	547:569	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	81	theme	rapid	428:432	arg1	monitoring					434:443	the direct and rapid monitoring	413:443	the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs)	413:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	0	82	theme	Graphene	8:15	arg1	Biosensors					33:42	Printed Graphene Electrochemical Biosensors	0:42	Printed Graphene Electrochemical Biosensors	0:42	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	6	83	theme	resulting	1139:1147	arg1	able					1163:1166	able	1163:1166	able	1163:1166	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	83	theme	resulting	1139:1147	arg1	biosensor					1149:1157	The resulting biosensor	1135:1157	The resulting biosensor	1135:1157	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	2	84	theme	direct	417:422	arg1	monitoring					434:443	the direct and rapid monitoring	413:443	the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs)	413:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	8	85	theme	OP	1773:1774	arg1	biosensors					1776:1785	OP biosensors	1773:1785	OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms	1773:1965	Hence, this work presents a scalable printed graphene manufacturing technique that can be used to create OP biosensors that are suitable for in-field applications as well as, more generally, for low-cost biosensor test strips that could be incorporated into wearable or disposable sensing paradigms.
29504744	2	86	theme	organophosphates	476:491	arg1	monitoring					434:443	the direct and rapid monitoring	413:443	the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs)	413:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	87	theme	linked	457:462	arg1	OPs					494:496	OPs	494:496	OPs	494:496	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	87	theme	linked	457:462	arg1	organophosphates					476:491	triple-O linked phosphonate organophosphates	448:491	triple-O linked phosphonate organophosphates (OPs)	448:497	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	7	88	dep	stability	1481:1489	arg1	%					1494:1494	90%	1492:1494	90% anodic current signal retention	1492:1526	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	3	89	theme	IML-printed	673:683	arg1	electrode					694:702	The IML-printed graphene electrode	669:702	The IML-printed graphene electrode	669:702	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	0	90	theme	Maskless	65:72	arg1	Lithography					74:84	Inkjet Maskless Lithography	58:84	Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates	58:138	Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates.
29504744	7	91	theme	signal	1511:1516	arg1	retention					1518:1526	anodic current signal retention	1496:1526	90% anodic current signal retention	1492:1526	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	5	92	theme	electrode	1083:1091	arg1	surface					1093:1099	the electrode surface	1079:1099	the electrode surface	1079:1099	The enzyme phosphotriesterase (PTE) was conjugated to the electrode surface via glutaraldehyde cross-linking.
29504744	6	93	theme	response	1192:1199	arg1	time					1201:1204	5 s response time	1188:1204	5 s response time	1188:1204	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	6	93	theme	response	1192:1199	arg1	paraoxon					1223:1230	the insecticide paraoxon	1207:1230	(5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM)	1187:1277	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	7	94	theme	anodic	1496:1501	arg1	retention					1518:1526	anodic current signal retention	1496:1526	90% anodic current signal retention	1492:1526	Moreover, the biosensor exhibited high reusability (average of 0.3% decrease in sensitivity per sensing event), stability (90% anodic current signal retention over 1000 s), longevity (70% retained sensitivity after 8 weeks), and the ability to selectively sense OP in actual soil and water samples.
29504744	6	95	theme	5	1188:1188	arg1	s					1190:1190	s	1190:1190	s	1190:1190	The resulting biosensor was able to rapidly measure (5 s response time) the insecticide paraoxon (a model OP) with a low detection limit (3 nM), and high sensitivity (370 nA/μM) with negligible interference from similar nerve agents.
29504744	2	96	theme	inkjet	375:380	arg1	lithography					391:401	inkjet maskless lithography	375:401	inkjet maskless lithography (IML)	375:407	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	2	96	theme	inkjet	375:380	arg1	IML					404:406	IML	404:406	IML	404:406	Here, we report a graphene-based electrode developed via inkjet maskless lithography (IML) for the direct and rapid monitoring of triple-O linked phosphonate organophosphates (OPs); these constitute the active compounds found in chemical warfare agents and pesticides that exhibit acute toxicity as well as long-term pollution to soils and waterways.
29504744	3	97	theme	laser	752:756	arg1	engraver					758:765	a 1000 mW benchtop laser engraver	733:765	a 1000 mW benchtop laser engraver	733:765	The IML-printed graphene electrode is nano/microstructured with a 1000 mW benchtop laser engraver and electrochemically deposited platinum nanoparticles (dia.
29504744	4	98	theme	electrical	851:860	arg1	conductivity					862:873	its electrical conductivity	847:873	its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq)	847:927	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	4	99	dep	100	919:921	arg1	to					916:917	to	916:917	to	916:917	∼25 nm) to improve its electrical conductivity (sheet resistance decreased from ∼10 000 to 100 Ω/sq), surface area, and electroactive nature for subsequent enzyme functionalization and biosensing.
29504744	1	100	theme	in-field	281:288	arg1	biosensors					306:315	in-field electrochemical biosensors	281:315	in-field electrochemical biosensors	281:315	Solution phase printing of graphene-based electrodes has recently become an attractive low-cost, scalable manufacturing technique to create in-field electrochemical biosensors.
30262754	2	0	from	donors	477:482	arg1	spermatozoa					438:448	swim-up purified and acrosome-reacted spermatozoa	400:448	swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors	400:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	0	from	donors	477:482	arg1	spermatozoa					360:370	ejaculated spermatozoa	349:370	ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors	349:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	3	1	dep	O-glycans	711:719	arg1	Tn					721:722	Tn	721:722	Tn	721:722	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	3	1	dep	O-glycans	711:719	arg1	O-glycans					711:719	the immature O-glycans	698:719	the immature O-glycans Tn and T	698:728	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	3	1	dep	O-glycans	711:719	arg1	T					728:728	T	728:728	T	728:728	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	2	2	theme	selected	523:530	arg1	men					532:534	206 randomly selected men	510:534	206 randomly selected men representing a broad spectrum of semen quality	510:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	7	3	theme	impaired	1502:1509	arg1	O-glycosylation					1511:1525	impaired O-glycosylation	1502:1525	impaired O-glycosylation of proteins	1502:1537	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	5	4	theme	motility	1103:1110	arg1	p					1112:1112	motility p	1103:1112	motility p = 1.8 × 10-5	1103:1125	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	4	theme	motility	1103:1110	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	1	5	theme	GalNAc-T3	159:167	arg1	expression					145:154	the expression	141:154	the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells,	141:227	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	2	6	from	expression	322:331	arg1	samples					497:503	semen samples	491:503	semen samples from 206 randomly selected men representing a broad spectrum of semen quality	491:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	6	from	expression	322:331	arg1	spermatozoa					360:370	ejaculated spermatozoa	349:370	ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors	349:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	6	from	expression	322:331	arg1	men					532:534	206 randomly selected men	510:534	206 randomly selected men representing a broad spectrum of semen quality	510:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	1	7	theme	qualitative	248:258	arg1	parameters					275:284	qualitative and functional parameters	248:284	qualitative and functional parameters of spermatozoa	248:299	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	2	8	theme	semen	569:573	arg1	quality					575:581	semen quality	569:581	semen quality	569:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	0	9	from	Expression	0:9	arg1	Segment					69:75	the Equatorial Segment	54:75	the Equatorial Segment	54:75	Expression of the O-Glycosylation Enzyme GalNAc-T3 in the Equatorial Segment Correlates with the Quality of Spermatozoa.
30262754	5	10	theme	semen	1028:1032	arg1	p					1112:1112	motility p	1103:1112	motility p = 1.8 × 10-5	1103:1125	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	10	theme	semen	1028:1032	arg1	p					1085:1085	morphology p	1074:1085	morphology p = 7 × 10-8	1074:1096	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	10	theme	semen	1028:1032	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	10	theme	semen	1028:1032	arg1	p					1060:1060	concentration p	1046:1060	concentration p = 9 × 10-6	1046:1071	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	3	11	theme	spermatozoa	769:779	arg1	segment					758:764	the equatorial segment	743:764	the equatorial segment of spermatozoa	743:779	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	4	12	theme	spermatozoa	819:829	arg1	proportion					786:795	The proportion	782:795	The proportion of GalNAc-T3-positive spermatozoa in the ejaculate	782:846	The proportion of GalNAc-T3-positive spermatozoa in the ejaculate increased after swim-up and appeared unaffected by induction of acrosomal exocytosis.
30262754	3	13	theme	donor	590:594	arg1	ejaculates					596:605	donor ejaculates	590:605	donor ejaculates	590:605	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	1	14	theme	functional	264:273	arg1	parameters					275:284	qualitative and functional parameters	248:284	qualitative and functional parameters of spermatozoa	248:299	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	0	15	theme	Spermatozoa	108:118	arg1	Quality					97:103	the Quality	93:103	the Quality of Spermatozoa	93:118	Expression of the O-Glycosylation Enzyme GalNAc-T3 in the Equatorial Segment Correlates with the Quality of Spermatozoa.
30262754	5	16	theme	GalNAc-T3	992:1000	arg1	expression					978:987	equatorial expression	967:987	equatorial expression of GalNAc-T3	967:1000	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	4	17	theme	acrosomal	912:920	arg1	exocytosis					922:931	acrosomal exocytosis	912:931	acrosomal exocytosis	912:931	The proportion of GalNAc-T3-positive spermatozoa in the ejaculate increased after swim-up and appeared unaffected by induction of acrosomal exocytosis.
30262754	2	18	theme	quality-control	455:469	arg1	donors					477:482	quality-control semen donors	455:482	quality-control semen donors	455:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	5	19	dep	=	1087:1087	arg1	×					1091:1091	7 × 10-8	1089:1096	7 × 10-8	1089:1096	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	2	20	theme	acrosome-reacted	421:436	arg1	spermatozoa					438:448	swim-up purified and acrosome-reacted spermatozoa	400:448	swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors	400:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	21	theme	broad	551:555	arg1	spectrum					557:564	a broad spectrum	549:564	a broad spectrum of semen quality	549:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	7	22	theme	GalNAc-T3	1480:1488	arg1	expression					1466:1475	reduced expression	1458:1475	reduced expression of GalNAc-T3	1458:1488	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	7	23	theme	reduced	1458:1464	arg1	expression					1466:1475	reduced expression	1458:1475	reduced expression of GalNAc-T3	1458:1488	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	3	24	dep	found	643:647	arg1	Using					584:588	Using	584:588	Using donor ejaculates and immunofluorescence detection	584:638	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	2	25	theme	semen	491:495	arg1	samples					497:503	semen samples	491:503	semen samples from 206 randomly selected men representing a broad spectrum of semen quality	491:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	26	from	spermatozoa	360:370	arg1	donors					477:482	quality-control semen donors	455:482	quality-control semen donors	455:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	26	from	spermatozoa	360:370	arg1	spermatozoa					438:448	swim-up purified and acrosome-reacted spermatozoa	400:448	swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors	400:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	3	27	theme	immunofluorescence	611:628	arg1	detection					630:638	immunofluorescence detection	611:638	immunofluorescence detection	611:638	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	2	28	theme	purified	408:415	arg1	spermatozoa					438:448	swim-up purified and acrosome-reacted spermatozoa	400:448	swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors	400:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	4	29	theme	exocytosis	922:931	arg1	induction					899:907	induction	899:907	induction of acrosomal exocytosis	899:931	The proportion of GalNAc-T3-positive spermatozoa in the ejaculate increased after swim-up and appeared unaffected by induction of acrosomal exocytosis.
30262754	4	30	from	proportion	786:795	arg1	ejaculate					838:846	the ejaculate	834:846	the ejaculate	834:846	The proportion of GalNAc-T3-positive spermatozoa in the ejaculate increased after swim-up and appeared unaffected by induction of acrosomal exocytosis.
30262754	7	31	theme	abnormal	1551:1558	arg1	maturation					1560:1569	abnormal maturation	1551:1569	abnormal maturation	1551:1569	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	1	32	theme	known	179:183	arg1	O-GalNAc-transferase					185:204	the only known O-GalNAc-transferase	170:204	the only known O-GalNAc-transferase present in germ cells	170:226	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	1	32	theme	known	179:183	arg1	GalNAc-T3					159:167	GalNAc-T3	159:167	GalNAc-T3	159:167	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	0	33	theme	O-Glycosylation	18:32	arg1	GalNAc-T3					41:49	the O-Glycosylation Enzyme GalNAc-T3	14:49	the O-Glycosylation Enzyme GalNAc-T3	14:49	Expression of the O-Glycosylation Enzyme GalNAc-T3 in the Equatorial Segment Correlates with the Quality of Spermatozoa.
30262754	7	34	theme	spermatozoa	1604:1614	arg1	maturation					1560:1569	abnormal maturation	1551:1569	abnormal maturation	1551:1569	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	7	34	theme	spermatozoa	1604:1614	arg1	functionality					1583:1595	reduced functionality	1575:1595	reduced functionality of the spermatozoa	1575:1614	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	4	35	theme	GalNAc-T3-positive	800:817	arg1	spermatozoa					819:829	GalNAc-T3-positive spermatozoa	800:829	GalNAc-T3-positive spermatozoa	800:829	The proportion of GalNAc-T3-positive spermatozoa in the ejaculate increased after swim-up and appeared unaffected by induction of acrosomal exocytosis.
30262754	6	36	theme	motile	1260:1265	arg1	spermatozoa					1267:1277	motile spermatozoa	1260:1277	motile spermatozoa	1260:1277	In conclusion, GalNAc-T3 was highly expressed by motile spermatozoa and the expression correlated positively with the classical semen parameters.
30262754	2	37	theme	semen	471:475	arg1	donors					477:482	quality-control semen donors	455:482	quality-control semen donors	455:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	1	38	theme	spermatozoa	289:299	arg1	parameters					275:284	qualitative and functional parameters	248:284	qualitative and functional parameters of spermatozoa	248:299	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	7	39	theme	proteins	1530:1537	arg1	O-glycosylation					1511:1525	impaired O-glycosylation	1502:1525	impaired O-glycosylation of proteins	1502:1537	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	2	40	from	men	532:534	arg1	samples					497:503	semen samples	491:503	semen samples from 206 randomly selected men representing a broad spectrum of semen quality	491:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	40	from	men	532:534	arg1	expression					322:331	the expression	318:331	the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality	318:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	5	41	theme	concentration	1046:1058	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	41	theme	concentration	1046:1058	arg1	p					1060:1060	concentration p	1046:1060	concentration p = 9 × 10-6	1046:1071	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	7	42	gly	O-glycosylation	1511:1525	arg1	proteins					1530:1537	proteins	1530:1537	proteins	1530:1537	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	1	43	theme	present	206:212	arg1	O-GalNAc-transferase					185:204	the only known O-GalNAc-transferase	170:204	the only known O-GalNAc-transferase present in germ cells	170:226	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	1	43	theme	present	206:212	arg1	GalNAc-T3					159:167	GalNAc-T3	159:167	GalNAc-T3	159:167	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	0	44	theme	GalNAc-T3	41:49	arg1	Expression					0:9	Expression	0:9	Expression of the O-Glycosylation Enzyme GalNAc-T3 in the Equatorial Segment	0:75	Expression of the O-Glycosylation Enzyme GalNAc-T3 in the Equatorial Segment Correlates with the Quality of Spermatozoa.
30262754	3	45	theme	immature	702:709	arg1	Tn					721:722	Tn	721:722	Tn	721:722	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	3	45	theme	immature	702:709	arg1	O-glycans					711:719	the immature O-glycans	698:719	the immature O-glycans Tn and T	698:728	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	3	45	theme	immature	702:709	arg1	T					728:728	T	728:728	T	728:728	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	5	46	theme	=	1087:1087	arg1	p					1085:1085	morphology p	1074:1085	morphology p = 7 × 10-8	1074:1096	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	46	theme	=	1087:1087	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	47	theme	spermatozoa	950:960	arg1	fraction					938:945	The fraction	934:945	The fraction of spermatozoa with equatorial expression of GalNAc-T3	934:1000	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	47	theme	spermatozoa	950:960	arg1	lower					1150:1154	lower	1150:1154	lower	1150:1154	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	0	48	theme	Enzyme	34:39	arg1	GalNAc-T3					41:49	the O-Glycosylation Enzyme GalNAc-T3	14:49	the O-Glycosylation Enzyme GalNAc-T3	14:49	Expression of the O-Glycosylation Enzyme GalNAc-T3 in the Equatorial Segment Correlates with the Quality of Spermatozoa.
30262754	2	49	theme	quality	575:581	arg1	spectrum					557:564	a broad spectrum	549:564	a broad spectrum of semen quality	549:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	7	50	theme	GalNAc-T3	1368:1376	arg1	expression					1378:1387	GalNAc-T3 expression	1368:1387	GalNAc-T3 expression	1368:1387	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	7	51	theme	spermatozoa	1425:1435	arg1	quality					1410:1416	the quality	1406:1416	the quality of the spermatozoa	1406:1435	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	1	52	theme	germ	217:220	arg1	cells					222:226	germ cells	217:226	germ cells	217:226	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	5	53	theme	=	1114:1114	arg1	p					1112:1112	motility p	1103:1112	motility p = 1.8 × 10-5	1103:1125	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	53	theme	=	1114:1114	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	7	54	theme	reduced	1575:1581	arg1	functionality					1583:1595	reduced functionality	1575:1595	reduced functionality of the spermatozoa	1575:1614	Therefore, GalNAc-T3 expression seems related to the quality of the spermatozoa, and we propose that reduced expression of GalNAc-T3 may lead to impaired O-glycosylation of proteins and thereby abnormal maturation and reduced functionality of the spermatozoa.
30262754	5	55	theme	=	1062:1062	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	55	theme	=	1062:1062	arg1	p					1060:1060	concentration p	1046:1060	concentration p = 9 × 10-6	1046:1071	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	6	56	theme	semen	1339:1343	arg1	parameters					1345:1354	the classical semen parameters	1325:1354	the classical semen parameters	1325:1354	In conclusion, GalNAc-T3 was highly expressed by motile spermatozoa and the expression correlated positively with the classical semen parameters.
30262754	2	57	theme	ejaculated	349:358	arg1	spermatozoa					360:370	ejaculated spermatozoa	349:370	ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors	349:482	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	5	58	dep	parameters	1034:1043	arg1	p					1112:1112	motility p	1103:1112	motility p = 1.8 × 10-5	1103:1125	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	58	dep	parameters	1034:1043	arg1	p					1085:1085	morphology p	1074:1085	morphology p = 7 × 10-8	1074:1096	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	58	dep	parameters	1034:1043	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	58	dep	parameters	1034:1043	arg1	p					1060:1060	concentration p	1046:1060	concentration p = 9 × 10-6	1046:1071	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	59	with	spermatozoa	950:960	arg1	expression					978:987	equatorial expression	967:987	equatorial expression of GalNAc-T3	967:1000	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	1	60	attach	present	206:212	arg2	GalNAc-T3					159:167	GalNAc-T3	159:167	GalNAc-T3	159:167	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	1	60	attach	present	206:212	arg1	cells					222:226	germ cells	217:226	germ cells	217:226	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	1	60	attach	present	206:212	arg2	O-GalNAc-transferase					185:204	the only known O-GalNAc-transferase	170:204	the only known O-GalNAc-transferase present in germ cells	170:226	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	5	61	theme	=	1200:1200	arg1	p					1198:1198	p = 0.0048	1198:1207	p = 0.0048	1198:1207	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	61	theme	=	1200:1200	arg1	oligoteratoasthenozoospermia					1168:1195	oligoteratoasthenozoospermia	1168:1195	oligoteratoasthenozoospermia (p = 0.0048)	1168:1208	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	1	62	from	cells	222:226	arg1	present					206:212	present	206:212	present	206:212	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	2	63	with	spermatozoa	360:370	arg1	immunocytochemistry					377:395	immunocytochemistry	377:395	immunocytochemistry	377:395	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	2	64	dep	purified	408:415	arg1	swim-up					400:406	swim-up	400:406	swim-up	400:406	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	1	65	from	present	206:212	arg1	cells					222:226	germ cells	217:226	germ cells	217:226	We question whether the expression of GalNAc-T3, the only known O-GalNAc-transferase present in germ cells, is correlated with qualitative and functional parameters of spermatozoa.
30262754	2	66	theme	GalNAc-T3	336:344	arg1	expression					322:331	the expression	318:331	the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality	318:581	We investigated the expression of GalNAc-T3 in ejaculated spermatozoa with immunocytochemistry in swim-up purified and acrosome-reacted spermatozoa from quality-control semen donors and in semen samples from 206 randomly selected men representing a broad spectrum of semen quality.
30262754	6	67	theme	classical	1329:1337	arg1	parameters					1345:1354	the classical semen parameters	1325:1354	the classical semen parameters	1325:1354	In conclusion, GalNAc-T3 was highly expressed by motile spermatozoa and the expression correlated positively with the classical semen parameters.
30262754	3	68	theme	O-glycans	711:719	arg1	presence					686:693	the presence	682:693	the presence of the immature O-glycans Tn and T	682:728	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	3	68	theme	O-glycans	711:719	arg1	expression					654:663	expression	654:663	expression of GalNAc-T3	654:676	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	5	69	theme	classical	1018:1026	arg1	p					1112:1112	motility p	1103:1112	motility p = 1.8 × 10-5	1103:1125	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	69	theme	classical	1018:1026	arg1	p					1085:1085	morphology p	1074:1085	morphology p = 7 × 10-8	1074:1096	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	69	theme	classical	1018:1026	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	69	theme	classical	1018:1026	arg1	p					1060:1060	concentration p	1046:1060	concentration p = 9 × 10-6	1046:1071	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	4	70	dep	appeared	876:883	arg1	unaffected					885:894	unaffected	885:894	appeared unaffected by induction of acrosomal exocytosis	876:931	The proportion of GalNAc-T3-positive spermatozoa in the ejaculate increased after swim-up and appeared unaffected by induction of acrosomal exocytosis.
30262754	5	71	theme	morphology	1074:1083	arg1	p					1085:1085	morphology p	1074:1085	morphology p = 7 × 10-8	1074:1096	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	71	theme	morphology	1074:1083	arg1	parameters					1034:1043	classical semen parameters	1018:1043	classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5)	1018:1126	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	72	dep	=	1062:1062	arg1	×					1066:1066	9 × 10-6	1064:1071	9 × 10-6	1064:1071	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	73	dep	=	1114:1114	arg1	×					1120:1120	1.8 × 10-5	1116:1125	1.8 × 10-5	1116:1125	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	0	74	theme	Equatorial	58:67	arg1	Segment					69:75	the Equatorial Segment	54:75	the Equatorial Segment	54:75	Expression of the O-Glycosylation Enzyme GalNAc-T3 in the Equatorial Segment Correlates with the Quality of Spermatozoa.
30262754	3	75	theme	GalNAc-T3	668:676	arg1	presence					686:693	the presence	682:693	the presence of the immature O-glycans Tn and T	682:728	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	3	75	theme	GalNAc-T3	668:676	arg1	expression					654:663	expression	654:663	expression of GalNAc-T3	654:676	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	3	76	theme	equatorial	747:756	arg1	segment					758:764	the equatorial segment	743:764	the equatorial segment of spermatozoa	743:779	Using donor ejaculates and immunofluorescence detection we found that expression of GalNAc-T3 and the presence of the immature O-glycans Tn and T localized to the equatorial segment of spermatozoa.
30262754	5	77	theme	equatorial	967:976	arg1	expression					978:987	equatorial expression	967:987	equatorial expression of GalNAc-T3	967:1000	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	78	with	men	1159:1161	arg1	p					1198:1198	p = 0.0048	1198:1207	p = 0.0048	1198:1207	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
30262754	5	78	with	men	1159:1161	arg1	oligoteratoasthenozoospermia					1168:1195	oligoteratoasthenozoospermia	1168:1195	oligoteratoasthenozoospermia (p = 0.0048)	1168:1208	The fraction of spermatozoa with equatorial expression of GalNAc-T3 correlated with classical semen parameters (concentration p = 9 × 10-6, morphology p = 7 × 10-8, and motility p = 1.8 × 10-5) and was significantly lower in men with oligoteratoasthenozoospermia (p = 0.0048).
31726007	1	0	theme	O-linked	142:149	arg1	GG-Hyl					213:218	GG-Hyl	213:218	GG-Hyl	213:218	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	0	theme	O-linked	142:149	arg1	G-					164:165	G-	164:165	G-	164:165	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	0	theme	O-linked	142:149	arg1	galactosyl-					151:161	O-linked galactosyl-	142:161	O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl)	142:219	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	6	1	theme	mass	923:926	arg1	analysis					942:949	mass spectrometric analysis	923:949	mass spectrometric analysis	923:949	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	3	2	theme	empty	619:623	arg1	vector					625:630	the empty vector	615:630	the empty vector	615:630	In Sh clones, the GLT25D1 protein levels were markedly diminished in comparison to controls (MC and those transfected with the empty vector).
31726007	5	3	theme	divalent	798:805	arg1	cross-links					807:817	immature divalent cross-links	789:817	immature divalent cross-links	789:817	In addition, the level of immature divalent cross-links significantly diminished while the level of the mature trivalent cross-link increased.
31726007	5	4	theme	cross-links	807:817	arg1	level					780:784	the level	776:784	the level of immature divalent cross-links	776:817	In addition, the level of immature divalent cross-links significantly diminished while the level of the mature trivalent cross-link increased.
31726007	1	5	theme	biological	235:244	arg1	significance					246:257	its biological significance	231:257	its biological significance	231:257	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	7	6	theme	glycosylation	1103:1115	arg1	sites					1117:1121	the glycosylation sites	1099:1121	the glycosylation sites	1099:1121	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	0	7	from	Role	0:3	arg1	Phenotypes					87:96	Molecular Phenotypes	77:96	Molecular Phenotypes	77:96	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	0	7	from	Role	0:3	arg1	Collagen					50:57	Type I Collagen Glycosylation and Molecular Phenotypes	43:96	Collagen	50:57	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	7	8	gly	glycosylation	1103:1115	arg2	sites					1117:1121	the glycosylation sites	1099:1121	the glycosylation sites	1099:1121	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	2	9	from	function	308:315	arg1	bone					341:344	bone	341:344	bone	341:344	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	4	10	theme	GG-Hyl	672:677	arg1	levels					650:655	levels	650:655	levels of both G- and GG-Hyl	650:677	In Sh collagen, levels of both G- and GG-Hyl were significantly diminished with a concomitant increase in the level of free-Hyl.
31726007	6	11	theme	helical	1054:1060	arg1	site					1076:1079	the helical cross-linking site	1050:1079	the helical cross-linking site	1050:1079	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	0	12	theme	Molecular	77:85	arg1	Phenotypes					87:96	Molecular Phenotypes	77:96	Molecular Phenotypes	77:96	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	5	13	theme	cross-link	884:893	arg1	level					854:858	the level	850:858	the level of the mature trivalent cross-link	850:893	In addition, the level of immature divalent cross-links significantly diminished while the level of the mature trivalent cross-link increased.
31726007	7	14	theme	G-	1147:1148	arg1	levels					1137:1142	the relative levels	1124:1142	the relative levels of G- and GG-Hyl	1124:1159	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	3	15	theme	Sh	495:496	arg1	clones					498:503	Sh clones	495:503	Sh clones	495:503	In Sh clones, the GLT25D1 protein levels were markedly diminished in comparison to controls (MC and those transfected with the empty vector).
31726007	4	16	theme	Sh	637:638	arg1	collagen					640:647	Sh collagen	637:647	Sh collagen	637:647	In Sh collagen, levels of both G- and GG-Hyl were significantly diminished with a concomitant increase in the level of free-Hyl.
31726007	4	17	theme	free-Hyl	753:760	arg1	level					744:748	the level	740:748	the level of free-Hyl	740:760	In Sh collagen, levels of both G- and GG-Hyl were significantly diminished with a concomitant increase in the level of free-Hyl.
31726007	7	18	theme	Lys	1262:1264	arg1	hydroxylation					1266:1278	Lys hydroxylation	1262:1278	Lys hydroxylation	1262:1278	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	2	19	theme	MC3T3-E1	379:386	arg1	clones					401:406	preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones,	365:434	clones	401:406	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	2	20	theme	gene	453:456	arg1	expression					458:467	Glt25d1 gene expression	445:467	Glt25d1 gene expression	445:467	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	2	21	dep	clones	401:406	arg1	clones					428:433	short hairpin (Sh) clones	409:433	short hairpin (Sh) clones	409:433	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	7	22	theme	hydroxylation	1266:1278	arg1	level					1253:1257	the level	1249:1257	the level of Lys hydroxylation	1249:1278	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	2	23	theme	preosteoblast	365:377	arg1	clones					401:406	preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones,	365:434	clones	401:406	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	2	24	theme	hairpin	415:421	arg1	clones					428:433	short hairpin (Sh) clones	409:433	short hairpin (Sh) clones	409:433	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	7	25	theme	relative	1128:1135	arg1	levels					1137:1142	the relative levels	1124:1142	the relative levels of G- and GG-Hyl	1124:1159	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	9	26	theme	mineralization	1597:1610	arg1	maturation					1538:1547	maturation	1538:1547	maturation of collagen cross-linking, fibrillogenesis, and mineralization	1538:1610	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	6	27	theme	type	997:1000	arg1	collagen					1004:1011	type I collagen	997:1011	type I collagen	997:1011	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	2	28	theme	short	409:413	arg1	Sh					424:425	Sh	424:425	Sh	424:425	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	2	28	theme	short	409:413	arg1	hairpin					415:421	short hairpin	409:421	short hairpin (Sh) clones	409:433	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	8	29	theme	Sh	1333:1334	arg1	clones					1336:1341	Sh clones	1333:1341	Sh clones	1333:1341	The collagen fibrils in Sh clones were larger, and mineralization was impaired.
31726007	3	30	theme	GLT25D1	510:516	arg1	levels					526:531	the GLT25D1 protein levels	506:531	the GLT25D1 protein levels	506:531	In Sh clones, the GLT25D1 protein levels were markedly diminished in comparison to controls (MC and those transfected with the empty vector).
31726007	1	31	theme	lesser	168:173	arg1	GG-Hyl					213:218	GG-Hyl	213:218	GG-Hyl	213:218	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	31	theme	lesser	168:173	arg1	G-					164:165	G-	164:165	G-	164:165	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	31	theme	lesser	168:173	arg1	galactosyl-					151:161	O-linked galactosyl-	142:161	O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl)	142:219	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	32	link	O-linked	142:149	arg1	GG-Hyl					213:218	GG-Hyl	213:218	GG-Hyl	213:218	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	32	link	O-linked	142:149	arg1	G-					164:165	G-	164:165	G-	164:165	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	32	link	O-linked	142:149	arg1	galactosyl-					151:161	O-linked galactosyl-	142:161	O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl)	142:219	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	9	33	theme	type	1473:1476	arg1	collagen					1480:1487	type I collagen	1473:1487	the type I collagen molecule	1469:1496	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	0	34	dep	Collagen	50:57	arg1	Glycosylation					59:71	Glycosylation	59:71	Glycosylation	59:71	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	2	35	theme	-derived	392:399	arg1	clones					401:406	preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones,	365:434	clones	401:406	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	0	36	theme	Glycosyltransferase	8:26	arg1	Domain					31:36	Glycosyltransferase 25 Domain 1	8:38	Glycosyltransferase 25 Domain 1	8:38	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	5	37	theme	mature	867:872	arg1	cross-link					884:893	the mature trivalent cross-link	863:893	the mature trivalent cross-link	863:893	In addition, the level of immature divalent cross-links significantly diminished while the level of the mature trivalent cross-link increased.
31726007	1	38	theme	glucosylgalactosyl-hydroxylysine	179:210	arg1	GG-Hyl					213:218	GG-Hyl	213:218	GG-Hyl	213:218	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	38	theme	glucosylgalactosyl-hydroxylysine	179:210	arg1	G-					164:165	G-	164:165	G-	164:165	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	38	theme	glucosylgalactosyl-hydroxylysine	179:210	arg1	galactosyl-					151:161	O-linked galactosyl-	142:161	O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl)	142:219	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	6	39	gly	glycosylation	958:970	arg2	seven					952:956	seven	952:956	seven	952:956	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	6	39	gly	glycosylation	958:970	arg2	sites					972:976	seven glycosylation sites	952:976	seven glycosylation sites	952:976	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	9	40	theme	collagen	1552:1559	arg1	cross-linking					1561:1573	collagen cross-linking	1552:1573	collagen cross-linking	1552:1573	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	9	41	theme	Hyl	1454:1456	arg1	galactosylation					1435:1449	galactosylation	1435:1449	galactosylation of Hyl	1435:1456	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	6	42	from	site	1076:1079	arg1	site					1038:1041	the most predominant site	1017:1041	the most predominant site	1017:1041	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	6	42	from	site	1076:1079	arg1	α1-87					1082:1086	α1-87	1082:1086	α1-87	1082:1086	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	2	43	theme	MC	389:390	arg1	clones					401:406	preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones,	365:434	clones	401:406	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	0	44	theme	Domain	31:36	arg1	Role					0:3	Role	0:3	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.	0:97	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	9	45	theme	collagen	1480:1487	arg1	molecule					1489:1496	the type I collagen molecule	1469:1496	the type I collagen molecule	1469:1496	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	8	46	theme	collagen	1313:1320	arg1	larger					1348:1353	larger	1348:1353	larger	1348:1353	The collagen fibrils in Sh clones were larger, and mineralization was impaired.
31726007	8	46	theme	collagen	1313:1320	arg1	fibrils					1322:1328	The collagen fibrils	1309:1328	The collagen fibrils in Sh clones	1309:1341	The collagen fibrils in Sh clones were larger, and mineralization was impaired.
31726007	7	47	theme	sites	1242:1246	arg1	five					1228:1231	five	1228:1231	five	1228:1231	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	7	47	theme	sites	1242:1246	arg1	sites					1242:1246	these sites	1236:1246	these sites	1236:1246	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	4	48	theme	G-	665:666	arg1	levels					650:655	levels	650:655	levels of both G- and GG-Hyl	650:677	In Sh collagen, levels of both G- and GG-Hyl were significantly diminished with a concomitant increase in the level of free-Hyl.
31726007	0	49	theme	Type	43:46	arg1	Collagen					50:57	Type I Collagen Glycosylation and Molecular Phenotypes	43:96	Collagen	50:57	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	8	50	from	fibrils	1322:1328	arg1	clones					1336:1341	Sh clones	1333:1341	Sh clones	1333:1341	The collagen fibrils in Sh clones were larger, and mineralization was impaired.
31726007	3	51	theme	protein	518:524	arg1	levels					526:531	the GLT25D1 protein levels	506:531	the GLT25D1 protein levels	506:531	In Sh clones, the GLT25D1 protein levels were markedly diminished in comparison to controls (MC and those transfected with the empty vector).
31726007	2	52	theme	modification	325:336	arg1	function					308:315	the function	304:315	the function of this modification in bone	304:344	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	9	53	theme	cross-linking	1561:1573	arg1	maturation					1538:1547	maturation	1538:1547	maturation of collagen cross-linking, fibrillogenesis, and mineralization	1538:1610	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	6	54	theme	cross-linking	1062:1074	arg1	site					1076:1079	the helical cross-linking site	1050:1079	the helical cross-linking site	1050:1079	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	7	55	theme	Sh	1208:1209	arg1	collagen					1211:1218	Sh collagen	1208:1218	Sh collagen	1208:1218	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	1	56	theme	type	116:119	arg1	collagen					123:130	type I collagen	116:130	type I collagen	116:130	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	9	57	theme	I	1478:1478	arg1	collagen					1480:1487	type I collagen	1473:1487	the type I collagen molecule	1469:1496	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	4	58	from	increase	728:735	arg1	level					744:748	the level	740:748	the level of free-Hyl	740:760	In Sh collagen, levels of both G- and GG-Hyl were significantly diminished with a concomitant increase in the level of free-Hyl.
31726007	1	59	theme	I	121:121	arg1	collagen					123:130	type I collagen	116:130	type I collagen	116:130	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	1	60	from	Glycosylation	99:111	arg1	collagen					123:130	type I collagen	116:130	type I collagen	116:130	Glycosylation in type I collagen occurs as O-linked galactosyl- (G-) lesser and glucosylgalactosyl-hydroxylysine (GG-Hyl); however, its biological significance is still not well understood.
31726007	3	61	dep	controls	575:582	arg1	MC					585:586	MC	585:586	MC	585:586	In Sh clones, the GLT25D1 protein levels were markedly diminished in comparison to controls (MC and those transfected with the empty vector).
31726007	3	61	dep	controls	575:582	arg1	those					592:596	those	592:596	those	592:596	In Sh clones, the GLT25D1 protein levels were markedly diminished in comparison to controls (MC and those transfected with the empty vector).
31726007	2	62	link	-derived	392:399	arg1	clones					401:406	preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones,	365:434	clones	401:406	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	5	63	theme	trivalent	874:882	arg1	cross-link					884:893	the mature trivalent cross-link	863:893	the mature trivalent cross-link	863:893	In addition, the level of immature divalent cross-links significantly diminished while the level of the mature trivalent cross-link increased.
31726007	7	64	theme	GG-Hyl	1154:1159	arg1	levels					1137:1142	the relative levels	1124:1142	the relative levels of G- and GG-Hyl	1124:1159	At all of the glycosylation sites, the relative levels of G- and GG-Hyl were markedly diminished, i.e., by ∼50-75%, in Sh collagen, and at five of these sites, the level of Lys hydroxylation was significantly increased.
31726007	2	65	theme	Glt25d1	445:451	arg1	expression					458:467	Glt25d1 gene expression	445:467	Glt25d1 gene expression	445:467	To investigate the function of this modification in bone, we have generated preosteoblast MC3T3-E1 (MC)-derived clones, short hairpin (Sh) clones, in which Glt25d1 gene expression was stably suppressed.
31726007	6	66	theme	glycosylation	958:970	arg1	sites					972:976	seven glycosylation sites	952:976	seven glycosylation sites	952:976	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	4	67	theme	concomitant	716:726	arg1	increase					728:735	a concomitant increase	714:735	a concomitant increase in the level of free-Hyl	714:760	In Sh collagen, levels of both G- and GG-Hyl were significantly diminished with a concomitant increase in the level of free-Hyl.
31726007	6	68	theme	predominant	1026:1036	arg1	α1-87					1082:1086	α1-87	1082:1086	α1-87	1082:1086	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	6	68	theme	predominant	1026:1036	arg1	site					1038:1041	the most predominant site	1017:1041	the most predominant site	1017:1041	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	6	69	theme	I	1002:1002	arg1	collagen					1004:1011	type I collagen	997:1011	type I collagen	997:1011	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31726007	0	70	theme	I	48:48	arg1	Collagen					50:57	Type I Collagen Glycosylation and Molecular Phenotypes	43:96	Collagen	50:57	Role of Glycosyltransferase 25 Domain 1 in Type I Collagen Glycosylation and Molecular Phenotypes.
31726007	5	71	theme	immature	789:796	arg1	cross-links					807:817	immature divalent cross-links	789:817	immature divalent cross-links	789:817	In addition, the level of immature divalent cross-links significantly diminished while the level of the mature trivalent cross-link increased.
31726007	9	72	theme	fibrillogenesis	1576:1590	arg1	maturation					1538:1547	maturation	1538:1547	maturation of collagen cross-linking, fibrillogenesis, and mineralization	1538:1610	These results indicate that GLT25D1 catalyzes galactosylation of Hyl throughout the type I collagen molecule and that this modification may regulate maturation of collagen cross-linking, fibrillogenesis, and mineralization.
31726007	6	73	theme	spectrometric	928:940	arg1	analysis					942:949	mass spectrometric analysis	923:949	mass spectrometric analysis	923:949	As determined by mass spectrometric analysis, seven glycosylation sites were identified in type I collagen and the most predominant site was at the helical cross-linking site, α1-87.
31176190	5	0	theme	release	800:806	arg1	analysis					781:788	a kinetic analysis	771:788	a kinetic analysis of glycan release from glycopeptides	771:825	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	5	1	theme	small-molecule	878:891	arg1	substrates					893:902	small-molecule substrates	878:902	small-molecule substrates	878:902	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	2	2	theme	substrate	354:362	arg1	molecule					364:371	the more complex substrate molecule	337:371	the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins	337:443	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	1	3	theme	cleavage	259:266	arg1	detection					246:254	easy detection	241:254	easy detection of cleavage of the glycoside bond	241:288	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	5	4	from	glycopeptides	813:825	arg1	analysis					781:788	a kinetic analysis	771:788	a kinetic analysis of glycan release from glycopeptides	771:825	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	5	4	from	glycopeptides	813:825	arg1	release					800:806	glycan release	793:806	glycan release from glycopeptides	793:825	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	2	5	gly	glycoproteins	431:443	arg1	glycoproteins					431:443	glycoproteins	431:443	glycoproteins	431:443	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	4	6	gly	glycoproteins	612:624	arg1	glycoproteins					612:624	glycoproteins	612:624	glycoproteins	612:624	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	2	7	theme	complex	346:352	arg1	molecule					364:371	the more complex substrate molecule	337:371	the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins	337:443	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	4	8	from	stoichiometry	711:723	arg1	terms					670:674	terms	670:674	terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility	670:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	7	9	theme	present	1381:1387	arg1	work					1389:1392	the present work	1377:1392	the present work	1377:1392	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	6	10	theme	GalNAc	1169:1174	arg1	release					1149:1155	the enzymatic release	1135:1155	the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase	1135:1231	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	7	11	theme	endo-α-N-acetylgalactosaminidase	1470:1501	arg1	properties					1456:1465	the kinetic properties	1444:1465	the kinetic properties of endo-α-N-acetylgalactosaminidase	1444:1501	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	2	12	theme	such	300:303	arg1	compounds					305:313	such compounds	300:313	such compounds	300:313	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	6	13	theme	variants	1053:1060	arg1	kinetics					1020:1027	the steady state kinetics	1003:1027	the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase	1003:1119	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	7	14	theme	reported	1293:1300	arg1	constants					1310:1318	previously reported kinetic constants	1282:1318	previously reported kinetic constants obtained with synthetic substrates	1282:1353	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	2	15	gly	glycopeptides	414:426	arg2	glycopeptides					414:426	glycopeptides	414:426	glycopeptides	414:426	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	4	16	theme	restricted	729:738	arg1	accessibility					747:759	restricted enzyme accessibility	729:759	restricted enzyme accessibility	729:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	1	17	theme	glycoside	275:283	arg1	bond					285:288	the glycoside bond	271:288	the glycoside bond	271:288	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	5	18	theme	kinetic	773:779	arg1	analysis					781:788	a kinetic analysis	771:788	a kinetic analysis of glycan release from glycopeptides	771:825	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	5	19	theme	complementary	853:865	arg1	information					841:851	information	841:851	information complementary to that of small-molecule substrates	841:902	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	4	20	from	heterogeneity	679:691	arg1	accessibility					747:759	restricted enzyme accessibility	729:759	restricted enzyme accessibility	729:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	4	20	from	heterogeneity	679:691	arg1	stoichiometry					711:723	stoichiometry	711:723	stoichiometry	711:723	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	6	21	theme	mutant	1046:1051	arg1	variants					1053:1060	mutant variants	1046:1060	mutant variants of Bifidobacterium longum	1046:1086	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	7	22	theme	kinetic	1302:1308	arg1	constants					1310:1318	previously reported kinetic constants	1282:1318	previously reported kinetic constants obtained with synthetic substrates	1282:1353	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	8	23	gly	glycopeptides	1681:1693	arg2	glycopeptides					1681:1693	glycopeptides	1681:1693	glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison	1681:1810	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	1	24	theme	interest	192:199	arg1	glycan					182:187	a glycan	180:187	a glycan of interest	180:199	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	0	25	theme	state	7:11	arg1	analysis					21:28	Steady state kinetic analysis	0:28	Steady state kinetic analysis of O-linked GalNAc glycan	0:54	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	8	26	theme	glycopeptides	1681:1693	arg1	glycoconjugates					1662:1676	glycoconjugates	1662:1676	glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison	1662:1810	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	6	27	theme	acid	1250:1253	arg1	units					1255:1259	sialic acid units	1243:1259	sialic acid units	1243:1259	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	4	28	from	terms	670:674	arg1	accessibility					747:759	restricted enzyme accessibility	729:759	restricted enzyme accessibility	729:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	4	28	from	terms	670:674	arg1	stoichiometry					711:723	stoichiometry	711:723	stoichiometry	711:723	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	5	29	theme	kinetic	929:935	arg1	parameters					937:946	kinetic parameters	929:946	kinetic parameters that are immediately comparable	929:978	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	0	30	theme	Steady	0:5	arg1	analysis					21:28	Steady state kinetic analysis	0:28	Steady state kinetic analysis of O-linked GalNAc glycan	0:54	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	1	31	theme	bond	285:288	arg1	cleavage					259:266	cleavage	259:266	cleavage of the glycoside bond	259:288	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	8	32	theme	state	1619:1623	arg1	KM					1645:1646	KM	1645:1646	KM	1645:1646	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	32	theme	state	1619:1623	arg1	parameters					1633:1642	the steady state kinetic parameters	1608:1642	the steady state kinetic parameters	1608:1642	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	32	theme	state	1619:1623	arg1	kcat					1652:1655	kcat	1652:1655	kcat	1652:1655	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	0	33	link	O-linked	33:40	arg1	glycan					49:54	O-linked GalNAc glycan	33:54	O-linked GalNAc glycan	33:54	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	6	34	theme	sialic	1243:1248	arg1	acid					1250:1253	sialic acid	1243:1253	sialic acid units	1243:1259	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	4	35	theme	heterogeneity	679:691	arg1	terms					670:674	terms	670:674	terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility	670:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	4	36	gly	glycopeptides	595:607	arg2	glycopeptides					595:607	glycopeptides	595:607	glycopeptides	595:607	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	1	37	theme	glycosidase	117:127	arg1	assays					129:134	glycosidase assays	117:134	glycosidase assays	117:134	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	4	38	from	complexity	656:665	arg1	terms					670:674	terms	670:674	terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility	670:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	2	39	theme	glycoproteins	431:443	arg1	glycoconjugates					395:409	glycoconjugates	395:409	glycoconjugates of glycopeptides or glycoproteins	395:443	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	0	40	theme	kinetic	13:19	arg1	analysis					21:28	Steady state kinetic analysis	0:28	Steady state kinetic analysis of O-linked GalNAc glycan	0:54	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	6	41	theme	wild	1032:1035	arg1	type					1037:1040	wild type	1032:1040	wild type	1032:1040	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	8	42	theme	substrate	1573:1581	arg1	concentration					1583:1595	the accessible substrate concentration	1558:1595	the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison	1558:1810	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	7	43	from	influence	1409:1417	arg1	properties					1456:1465	the kinetic properties	1444:1465	the kinetic properties of endo-α-N-acetylgalactosaminidase	1444:1501	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	0	44	dep	release	56:62	arg1	catalyzed					64:72	catalyzed	64:72	release catalyzed by endo-α-N-acetylgalactosaminidase	56:108	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	6	45	theme	enzymatic	1139:1147	arg1	release					1149:1155	the enzymatic release	1135:1155	the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase	1135:1231	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	0	46	theme	O-linked	33:40	arg1	glycan					49:54	O-linked GalNAc glycan	33:54	O-linked GalNAc glycan	33:54	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	7	47	theme	peptide	1426:1432	arg1	moiety					1434:1439	the peptide moiety	1422:1439	the peptide moiety	1422:1439	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	5	48	from	analysis	781:788	arg1	glycopeptides					813:825	glycopeptides	813:825	glycopeptides	813:825	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	8	49	theme	data	1526:1529	arg1	method					1540:1545	The devised assay and data handling method	1504:1545	method	1540:1545	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	7	50	theme	moiety	1434:1439	arg1	influence					1409:1417	an influence	1406:1417	an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase	1406:1501	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	2	51	theme	glycopeptides	414:426	arg1	glycoconjugates					395:409	glycoconjugates	395:409	glycoconjugates of glycopeptides or glycoproteins	395:443	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	8	52	theme	same	1712:1715	arg1	units					1717:1721	the same units	1708:1721	the same units as obtained from using small-molecule substrates and thus allows for a direct comparison	1708:1810	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	1	53	attach	linked	204:209	arg2	glycan					182:187	a glycan	180:187	a glycan of interest	180:199	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	1	53	attach	linked	204:209	arg1	chromophore					216:226	a chromophore	214:226	a chromophore allowing for easy detection of cleavage of the glycoside bond	214:288	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	6	54	theme	Galβ	1160:1163	arg1	GalNAc					1169:1174	Galβ(1-3)GalNAc	1160:1174	Galβ(1-3)GalNAc	1160:1174	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	0	55	theme	glycan	49:54	arg1	analysis					21:28	Steady state kinetic analysis	0:28	Steady state kinetic analysis of O-linked GalNAc glycan	0:54	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	6	56	theme	state	1014:1018	arg1	kinetics					1020:1027	the steady state kinetics	1003:1027	the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase	1003:1119	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	6	57	theme	type	1037:1040	arg1	kinetics					1020:1027	the steady state kinetics	1003:1027	the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase	1003:1119	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	6	58	theme	bovine	1181:1186	arg1	glycomacropeptide					1188:1204	bovine glycomacropeptide	1181:1204	bovine glycomacropeptide pre-treated with sialidase	1181:1231	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	0	59	theme	GalNAc	42:47	arg1	glycan					49:54	O-linked GalNAc glycan	33:54	O-linked GalNAc glycan	33:54	Steady state kinetic analysis of O-linked GalNAc glycan release catalyzed by endo-α-N-acetylgalactosaminidase.
31176190	6	60	theme	steady	1007:1012	arg1	kinetics					1020:1027	the steady state kinetics	1003:1027	the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase	1003:1119	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	8	61	theme	steady	1612:1617	arg1	KM					1645:1646	KM	1645:1646	KM	1645:1646	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	61	theme	steady	1612:1617	arg1	parameters					1633:1642	the steady state kinetic parameters	1608:1642	the steady state kinetic parameters	1608:1642	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	61	theme	steady	1612:1617	arg1	kcat					1652:1655	kcat	1652:1655	kcat	1652:1655	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	62	theme	handling	1531:1538	arg1	method					1540:1545	The devised assay and data handling method	1504:1545	method	1540:1545	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	4	63	theme	enzyme	740:745	arg1	accessibility					747:759	restricted enzyme accessibility	729:759	restricted enzyme accessibility	729:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	8	64	theme	accessible	1562:1571	arg1	concentration					1583:1595	the accessible substrate concentration	1558:1595	the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison	1558:1810	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	6	65	from	glycomacropeptide	1188:1204	arg1	release					1149:1155	the enzymatic release	1135:1155	the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase	1135:1231	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	8	66	theme	devised	1508:1514	arg1	assay					1516:1520	The devised assay and data handling method	1504:1545	assay	1516:1520	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	4	67	theme	protein-glycan	696:709	arg1	stoichiometry					711:723	stoichiometry	711:723	stoichiometry	711:723	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	3	68	theme	enzyme	487:492	arg1	activity					494:501	enzyme activity	487:501	enzyme activity	487:501	Nonetheless, the advantage is obvious as enzyme activity is readily recorded and kinetic parameters easily obtained.
31176190	8	69	theme	kinetic	1625:1631	arg1	KM					1645:1646	KM	1645:1646	KM	1645:1646	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	69	theme	kinetic	1625:1631	arg1	parameters					1633:1642	the steady state kinetic parameters	1608:1642	the steady state kinetic parameters	1608:1642	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	69	theme	kinetic	1625:1631	arg1	kcat					1652:1655	kcat	1652:1655	kcat	1652:1655	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	5	70	gly	glycopeptides	813:825	arg2	glycopeptides					813:825	glycopeptides	813:825	glycopeptides	813:825	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	1	71	theme	small-molecule	149:162	arg1	compounds					164:172	small-molecule compounds	149:172	small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond	149:288	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	4	72	from	accessibility	747:759	arg1	terms					670:674	terms	670:674	terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility	670:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	1	73	theme	easy	241:244	arg1	detection					246:254	easy detection	241:254	easy detection of cleavage of the glycoside bond	241:288	Often glycosidase assays are based on small-molecule compounds where a glycan of interest is linked to a chromophore allowing for easy detection of cleavage of the glycoside bond.
31176190	7	74	theme	synthetic	1334:1342	arg1	substrates					1344:1353	synthetic substrates	1334:1353	synthetic substrates	1334:1353	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	6	75	dep	type	1037:1040	arg1	endo-α-N-acetylgalactosaminidase					1088:1119	endo-α-N-acetylgalactosaminidase	1088:1119	endo-α-N-acetylgalactosaminidase	1088:1119	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	7	76	theme	kinetic	1448:1454	arg1	properties					1456:1465	the kinetic properties	1444:1465	the kinetic properties of endo-α-N-acetylgalactosaminidase	1444:1501	Differences between previously reported kinetic constants obtained with synthetic substrates and those obtained in the present work demonstrate an influence of the peptide moiety on the kinetic properties of endo-α-N-acetylgalactosaminidase.
31176190	4	77	theme	increased	646:654	arg1	complexity					656:665	increased complexity	646:665	increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility	646:759	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	3	78	theme	kinetic	527:533	arg1	parameters					535:544	kinetic parameters	527:544	kinetic parameters	527:544	Nonetheless, the advantage is obvious as enzyme activity is readily recorded and kinetic parameters easily obtained.
31176190	8	79	theme	direct	1794:1799	arg1	comparison					1801:1810	a direct comparison	1792:1810	a direct comparison	1792:1810	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	8	80	theme	small-molecule	1746:1759	arg1	substrates					1761:1770	small-molecule substrates	1746:1770	small-molecule substrates	1746:1770	The devised assay and data handling method determines the accessible substrate concentration as well as the steady state kinetic parameters, KM and kcat, for glycoconjugates of glycopeptides described by the same units as obtained from using small-molecule substrates and thus allows for a direct comparison.
31176190	5	81	theme	glycan	793:798	arg1	release					800:806	glycan release	793:806	glycan release from glycopeptides	793:825	However, a kinetic analysis of glycan release from glycopeptides could provide information complementary to that of small-molecule substrates, especially if providing kinetic parameters that are immediately comparable.
31176190	4	82	with	case	585:588	arg1	glycopeptides					595:607	glycopeptides	595:607	glycopeptides	595:607	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	4	82	with	case	585:588	arg1	glycoproteins					612:624	glycoproteins	612:624	glycoproteins	612:624	This is not often the case with glycopeptides or glycoproteins as these may reveal increased complexity in terms of heterogeneity in protein-glycan stoichiometry and restricted enzyme accessibility.
31176190	2	83	theme	molecule	364:371	arg1	part					329:332	part	329:332	part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins	329:443	However, such compounds only resemble part of the more complex substrate molecule for enzymes acting on glycoconjugates of glycopeptides or glycoproteins.
31176190	6	84	theme	longum	1081:1086	arg1	type					1037:1040	wild type	1032:1040	wild type	1032:1040	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
31176190	6	84	theme	longum	1081:1086	arg1	variants					1053:1060	mutant variants	1046:1060	mutant variants of Bifidobacterium longum	1046:1086	We have characterized the steady state kinetics of wild type and mutant variants of Bifidobacterium longum endo-α-N-acetylgalactosaminidase, by recording the enzymatic release of Galβ(1-3)GalNAc from bovine glycomacropeptide pre-treated with sialidase to remove sialic acid units.
30504378	0	0	theme	Cell	87:90	arg1	Lines					92:96	Human Cancer Cell Lines	74:96	Human Cancer Cell Lines	74:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	2	1	theme	O-GlcNAc	505:512	arg1	levels					514:519	global O-GlcNAc levels	498:519	global O-GlcNAc levels	498:519	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	2	2	theme	chain	638:642	arg1	reaction					644:651	real-time quantitative polymerase chain reaction	604:651	real-time quantitative polymerase chain reaction	604:651	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	2	3	theme	METHODS	335:341	arg1	cultures					348:355	MATERIALS AND METHODS Cell cultures	321:355	MATERIALS AND METHODS Cell cultures	321:355	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	4	4	theme	HT-29	907:911	arg1	cells					913:917	resting HL-60 and HT-29 cells	889:917	cells	913:917	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	1	5	theme	expression	242:251	arg1	profiles					253:260	galectin gene expression profiles	228:260	galectin gene expression profiles	228:260	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	0	6	theme	Cancer	80:85	arg1	Lines					92:96	Human Cancer Cell Lines	74:96	Human Cancer Cell Lines	74:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	2	7	theme	polymerase	627:636	arg1	reaction					644:651	real-time quantitative polymerase chain reaction	604:651	real-time quantitative polymerase chain reaction	604:651	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	1	8	theme	transferase	174:184	arg1	effects					118:124	BACKGROUND/AIM The effects	99:124	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles	99:260	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	2	9	theme	genes	548:552	arg1	levels					514:519	global O-GlcNAc levels	498:519	global O-GlcNAc levels	498:519	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	2	9	theme	genes	548:552	arg1	expression					525:534	expression	525:534	expression of galectin genes	525:552	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	0	10	from	Effects	0:6	arg1	Profiles					62:69	Galectin Gene-expression Profiles	37:69	Galectin Gene-expression Profiles in Human Cancer Cell Lines	37:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	2	11	theme	quantitative	614:625	arg1	reaction					644:651	real-time quantitative polymerase chain reaction	604:651	real-time quantitative polymerase chain reaction	604:651	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	6	12	theme	O-GlcNAc-dependent	1185:1202	arg1	mechanisms					1204:1213	Additional O-GlcNAc-dependent mechanisms	1174:1213	Additional O-GlcNAc-dependent mechanisms	1174:1213	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	4	13	theme	enterocytic	1001:1011	arg1	lineages					1013:1020	neutrophilic or enterocytic lineages	985:1020	neutrophilic or enterocytic lineages	985:1020	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	2	14	theme	galectin	539:546	arg1	genes					548:552	galectin genes	539:552	galectin genes	539:552	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	0	15	from	Profiles	62:69	arg1	Lines					92:96	Human Cancer Cell Lines	74:96	Human Cancer Cell Lines	74:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	2	16	theme	real-time	604:612	arg1	reaction					644:651	real-time quantitative polymerase chain reaction	604:651	real-time quantitative polymerase chain reaction	604:651	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	5	17	theme	galectin	1158:1165	arg1	genes					1167:1171	galectin genes	1158:1171	galectin genes	1158:1171	CONCLUSION O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes.
30504378	4	18	from	levels	867:872	arg1	cells					913:917	resting HL-60 and HT-29 cells	889:917	cells	913:917	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	4	18	from	levels	867:872	arg1	HL-60					897:901	resting HL-60 and HT-29 cells	889:917	HL-60	897:901	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	4	19	theme	basal	861:865	arg1	levels					867:872	basal levels	861:872	basal levels of O-GlcNAc in resting HL-60 and HT-29 cells	861:917	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	2	20	theme	inhibitor	415:423	arg1	2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose					425:491	OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose	411:491	OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose	411:491	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	5	21	theme	number	1148:1153	arg1	expression					1119:1128	the expression	1115:1128	the expression of only a limited number of galectin genes	1115:1171	CONCLUSION O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes.
30504378	3	22	from	LGALS12	707:713	arg1	cells					724:728	HL-60 cells	718:728	HL-60 cells	718:728	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	3	22	from	LGALS12	707:713	arg1	cells					697:701	MCF7 cells	692:701	MCF7 cells	692:701	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	5	23	theme	limited	1140:1146	arg1	number					1148:1153	only a limited number	1133:1153	only a limited number of galectin genes	1133:1171	CONCLUSION O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes.
30504378	3	24	theme	cell-specific	776:788	arg1	galectins					790:798	other cell-specific galectins	770:798	other cell-specific galectins	770:798	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	2	25	theme	OGT	411:413	arg1	2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose					425:491	OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose	411:491	OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose	411:491	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	2	26	theme	global	498:503	arg1	levels					514:519	global O-GlcNAc levels	498:519	global O-GlcNAc levels	498:519	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	6	27	theme	further	1309:1315	arg1	investigation					1317:1329	further investigation	1309:1329	further investigation	1309:1329	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	3	28	from	changes	821:827	arg1	level					841:845	O-GlcNAc level	832:845	O-GlcNAc level	832:845	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	6	29	dep	work	1219:1222	arg1	secretion					1255:1263	galectin secretion	1246:1263	galectin secretion	1246:1263	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	6	29	dep	work	1219:1222	arg1	localization					1283:1294	intracellular localization	1269:1294	intracellular localization	1269:1294	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	6	30	theme	Additional	1174:1183	arg1	mechanisms					1204:1213	Additional O-GlcNAc-dependent mechanisms	1174:1213	Additional O-GlcNAc-dependent mechanisms	1174:1213	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	1	31	from	effects	118:124	arg1	profiles					253:260	galectin gene expression profiles	228:260	galectin gene expression profiles	228:260	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	4	32	theme	O-GlcNAc	877:884	arg1	levels					867:872	basal levels	861:872	basal levels of O-GlcNAc in resting HL-60 and HT-29 cells	861:917	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	0	33	theme	O-GlcNAcylation	18:32	arg1	Effects					0:6	Effects	0:6	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines	0:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	2	34	theme	Cell	343:346	arg1	cultures					348:355	MATERIALS AND METHODS Cell cultures	321:355	MATERIALS AND METHODS Cell cultures	321:355	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	1	35	theme	O-GlcNAcase	196:206	arg1	inhibitors					214:223	O-GlcNAcase (OGA) inhibitors	196:223	O-GlcNAcase (OGA) inhibitors	196:223	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	0	36	theme	Global	11:16	arg1	O-GlcNAcylation					18:32	Global O-GlcNAcylation	11:32	Global O-GlcNAcylation	11:32	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	5	37	theme	genes	1167:1171	arg1	number					1148:1153	only a limited number	1133:1153	only a limited number of galectin genes	1133:1171	CONCLUSION O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes.
30504378	1	38	theme	The	114:116	arg1	effects					118:124	BACKGROUND/AIM The effects	99:124	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles	99:260	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	2	39	theme	OGA	384:386	arg1	G					406:406	OGA inhibitor thiamet G	384:406	OGA inhibitor thiamet G	384:406	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	0	40	theme	Galectin	37:44	arg1	Profiles					62:69	Galectin Gene-expression Profiles	37:69	Galectin Gene-expression Profiles in Human Cancer Cell Lines	37:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	5	41	theme	CONCLUSION	1037:1046	arg1	pathways					1076:1083	CONCLUSION O-GlcNAc-mediated signaling pathways	1037:1083	CONCLUSION O-GlcNAc-mediated signaling pathways	1037:1083	CONCLUSION O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes.
30504378	5	42	theme	O-GlcNAc-mediated	1048:1064	arg1	pathways					1076:1083	CONCLUSION O-GlcNAc-mediated signaling pathways	1037:1083	CONCLUSION O-GlcNAc-mediated signaling pathways	1037:1083	CONCLUSION O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes.
30504378	3	43	dep	RESULTS	654:660	arg1	up-regulated					736:747	up-regulated	736:747	up-regulated by O-GlcNAc	736:759	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	6	44	theme	protein	1231:1237	arg1	level					1239:1243	the protein level	1227:1243	the protein level	1227:1243	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	3	45	theme	galectin	666:673	arg1	LGALS12					707:713	LGALS12	707:713	LGALS12 in HL-60 cells	707:728	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	3	45	theme	galectin	666:673	arg1	LGALS3					682:687	LGALS3	682:687	LGALS3 in MCF7 cells	682:701	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	3	45	theme	galectin	666:673	arg1	genes					675:679	Two galectin genes	662:679	Two galectin genes	662:679	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	5	46	theme	signaling	1066:1074	arg1	pathways					1076:1083	CONCLUSION O-GlcNAc-mediated signaling pathways	1037:1083	CONCLUSION O-GlcNAc-mediated signaling pathways	1037:1083	CONCLUSION O-GlcNAc-mediated signaling pathways may be involved in regulating the expression of only a limited number of galectin genes.
30504378	3	47	from	LGALS3	682:687	arg1	cells					724:728	HL-60 cells	718:728	HL-60 cells	718:728	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	3	47	from	LGALS3	682:687	arg1	cells					697:701	MCF7 cells	692:701	MCF7 cells	692:701	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	1	48	link	O-linked	129:136	arg1	OGT					187:189	OGT	187:189	OGT	187:189	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	1	48	link	O-linked	129:136	arg1	transferase					174:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	129:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	129:190	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	3	49	theme	other	770:774	arg1	galectins					790:798	other cell-specific galectins	770:798	other cell-specific galectins	770:798	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	2	50	theme	MATERIALS	321:329	arg1	cultures					348:355	MATERIALS AND METHODS Cell cultures	321:355	MATERIALS AND METHODS Cell cultures	321:355	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	0	51	theme	Gene-expression	46:60	arg1	Profiles					62:69	Galectin Gene-expression Profiles	37:69	Galectin Gene-expression Profiles in Human Cancer Cell Lines	37:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	1	52	theme	HL-60	296:300	arg1	lines					314:318	HL-60 cancer cell lines	296:318	HL-60 cancer cell lines	296:318	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	3	53	theme	HL-60	718:722	arg1	cells					724:728	HL-60 cells	718:728	HL-60 cells	718:728	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	6	54	theme	intracellular	1269:1281	arg1	localization					1283:1294	intracellular localization	1269:1294	intracellular localization	1269:1294	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	1	55	theme	cancer	302:307	arg1	lines					314:318	HL-60 cancer cell lines	296:318	HL-60 cancer cell lines	296:318	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	2	56	theme	blot	589:592	arg1	assay					594:598	an immunodot blot assay	576:598	an immunodot blot assay	576:598	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	1	57	theme	O-linked	129:136	arg1	OGT					187:189	OGT	187:189	OGT	187:189	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	1	57	theme	O-linked	129:136	arg1	transferase					174:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	129:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	129:190	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	1	58	theme	inhibitors	214:223	arg1	effects					118:124	BACKGROUND/AIM The effects	99:124	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles	99:260	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	2	59	theme	immunodot	579:587	arg1	assay					594:598	an immunodot blot assay	576:598	an immunodot blot assay	576:598	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	1	60	theme	β-N-acetyl-D-glucosamine	138:161	arg1	OGT					187:189	OGT	187:189	OGT	187:189	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	1	60	theme	β-N-acetyl-D-glucosamine	138:161	arg1	transferase					174:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	129:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	129:190	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	4	61	theme	resting	889:895	arg1	HL-60					897:901	resting HL-60 and HT-29 cells	889:917	HL-60	897:901	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	3	62	theme	O-GlcNAc	832:839	arg1	level					841:845	O-GlcNAc level	832:845	O-GlcNAc level	832:845	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	0	63	theme	Human	74:78	arg1	Lines					92:96	Human Cancer Cell Lines	74:96	Human Cancer Cell Lines	74:96	Effects of Global O-GlcNAcylation on Galectin Gene-expression Profiles in Human Cancer Cell Lines.
30504378	3	64	theme	MCF7	692:695	arg1	cells					697:701	MCF7 cells	692:701	MCF7 cells	692:701	RESULTS Two galectin genes, LGALS3 in MCF7 cells and LGALS12 in HL-60 cells, were up-regulated by O-GlcNAc, whereas other cell-specific galectins were unresponsive to changes in O-GlcNAc level.
30504378	6	65	theme	galectin	1246:1253	arg1	secretion					1255:1263	galectin secretion	1246:1263	galectin secretion	1246:1263	Additional O-GlcNAc-dependent mechanisms may work at the protein level (galectin secretion and intracellular localization) and warrant further investigation.
30504378	2	66	theme	inhibitor	388:396	arg1	G					406:406	OGA inhibitor thiamet G	384:406	OGA inhibitor thiamet G	384:406	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	1	67	theme	galectin	228:235	arg1	profiles					253:260	galectin gene expression profiles	228:260	galectin gene expression profiles	228:260	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	4	68	theme	neutrophilic	985:996	arg1	lineages					1013:1020	neutrophilic or enterocytic lineages	985:1020	neutrophilic or enterocytic lineages	985:1020	Of interest, basal levels of O-GlcNAc in resting HL-60 and HT-29 cells were significantly higher than those in cells differentiated into neutrophilic or enterocytic lineages, respectively.
30504378	1	69	theme	cell	309:312	arg1	lines					314:318	HL-60 cancer cell lines	296:318	HL-60 cancer cell lines	296:318	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	2	70	theme	thiamet	398:404	arg1	G					406:406	OGA inhibitor thiamet G	384:406	OGA inhibitor thiamet G	384:406	MATERIALS AND METHODS Cell cultures were treated for 24 h with OGA inhibitor thiamet G or OGT inhibitor 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-5-thio-α-D-glucopyranose, and global O-GlcNAc levels and expression of galectin genes were determined using an immunodot blot assay and real-time quantitative polymerase chain reaction.
30504378	1	71	theme	O-GlcNAc	164:171	arg1	OGT					187:189	OGT	187:189	OGT	187:189	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	1	71	theme	O-GlcNAc	164:171	arg1	transferase					174:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase	129:184	O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT)	129:190	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
30504378	1	72	theme	gene	237:240	arg1	profiles					253:260	galectin gene expression profiles	228:260	galectin gene expression profiles	228:260	BACKGROUND/AIM The effects of O-linked β-N-acetyl-D-glucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA) inhibitors on galectin gene expression profiles were examined in MCF7, HT-29, and HL-60 cancer cell lines.
29515119	0	0	theme	cancer	82:87	arg1	arrest					96:101	breast cancer growth arrest	75:101	breast cancer growth arrest	75:101	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.
29515119	5	1	theme	Negative	713:720	arg1	TNBC					737:740	TNBC	737:740	TNBC	737:740	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	5	1	theme	Negative	713:720	arg1	Cancer					729:734	Triple Negative Breast Cancer	706:734	Triple Negative Breast Cancer (TNBC) cells	706:747	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	1	2	theme	protein	150:156	arg1	glycosylation					158:170	O-linked protein glycosylation	141:170	O-linked protein glycosylation	141:170	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	0	3	theme	breast	75:80	arg1	arrest					96:101	breast cancer growth arrest	75:101	breast cancer growth arrest	75:101	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.
29515119	7	4	theme	cancer	1392:1397	arg1	therapy					1399:1405	breast cancer therapy	1385:1405	breast cancer therapy	1385:1405	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	5	5	dep	N-	841:842	arg1	level					864:868	level	864:868	level	864:868	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	6	6	theme	ROS	1128:1130	arg1	Response					1079:1086	the Unfolded Protein Response	1058:1086	the Unfolded Protein Response (UPR)	1058:1092	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	6	6	theme	ROS	1128:1130	arg1	UPR					1089:1091	UPR	1089:1091	UPR	1089:1091	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	6	6	theme	ROS	1128:1130	arg1	accumulation					1098:1109	accumulation	1098:1109	accumulation of intracellular ROS	1098:1130	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	3	7	theme	PGM3	514:517	arg1	inhibitor					486:494	a novel inhibitor	478:494	a novel inhibitor of the HBP enzyme PGM3	478:517	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	3	7	theme	PGM3	514:517	arg1	FR054					471:475	FR054	471:475	FR054	471:475	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	5	8	theme	strong	888:893	arg1	reduction					895:903	a strong reduction	886:903	a strong reduction of cancer cell adhesion and migration	886:941	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	0	9	theme	growth	89:94	arg1	arrest					96:101	breast cancer growth arrest	75:101	breast cancer growth arrest	75:101	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.
29515119	3	10	theme	novel	480:484	arg1	inhibitor					486:494	a novel inhibitor	478:494	a novel inhibitor of the HBP enzyme PGM3	478:517	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	3	10	theme	novel	480:484	arg1	FR054					471:475	FR054	471:475	FR054	471:475	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	4	11	from	decrease	632:639	arg1	cell					644:647	cell proliferation and survival	644:674	cell proliferation and survival	644:674	In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival.
29515119	7	12	theme	breast	1385:1390	arg1	therapy					1399:1405	breast cancer therapy	1385:1405	breast cancer therapy	1385:1405	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	3	13	theme	HBP	503:505	arg1	PGM3					514:517	the HBP enzyme PGM3	499:517	the HBP enzyme PGM3	499:517	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	5	14	theme	O-glycosylation	848:862	arg1	reduction					823:831	FR054-dependent reduction	807:831	FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration	807:941	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	6	15	theme	FR054	1005:1009	arg1	treatment					1011:1019	FR054 treatment	1005:1019	FR054 treatment	1005:1019	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	7	16	theme	promising	1362:1370	arg1	compound					1372:1379	a promising compound	1360:1379	a promising compound for breast cancer therapy	1360:1405	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	5	17	theme	Cancer	729:734	arg1	cells					743:747	Triple Negative Breast Cancer (TNBC) cells	706:747	Triple Negative Breast Cancer (TNBC) cells	706:747	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	7	18	from	growth	1179:1184	arg1	mice					1210:1213	MDA-MB-231 xenograft mice	1189:1213	MDA-MB-231 xenograft mice	1189:1213	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	3	19	theme	enzyme	507:512	arg1	PGM3					514:517	the HBP enzyme PGM3	499:517	the HBP enzyme PGM3	499:517	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	2	20	theme	inhibitors	373:382	arg1	toxicity					344:351	toxicity	344:351	toxicity	344:351	However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment.
29515119	2	20	theme	inhibitors	373:382	arg1	specificity					328:338	low specificity	324:338	low specificity	324:338	However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment.
29515119	5	21	theme	cells	743:747	arg1	model					697:701	a model	695:701	a model of Triple Negative Breast Cancer (TNBC) cells	695:747	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	5	21	theme	cells	743:747	arg1	MDA-MB-231					750:759	MDA-MB-231	750:759	MDA-MB-231	750:759	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	5	22	theme	Breast	722:727	arg1	TNBC					737:740	TNBC	737:740	TNBC	737:740	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	5	22	theme	Breast	722:727	arg1	Cancer					729:734	Triple Negative Breast Cancer	706:734	Triple Negative Breast Cancer (TNBC) cells	706:747	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	7	23	theme	cancer	1172:1177	arg1	growth					1179:1184	cancer growth	1172:1184	cancer growth in MDA-MB-231 xenograft mice	1172:1213	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	3	24	theme	remarkable	527:536	arg1	effect					557:562	a remarkable anti-breast cancer effect	525:562	a remarkable anti-breast cancer effect	525:562	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	6	25	theme	cells	994:998	arg1	survival					975:982	impaired survival	966:982	impaired survival of cancer cells upon FR054 treatment	966:1019	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	2	26	theme	HBP	369:371	arg1	inhibitors					373:382	the existing HBP inhibitors	356:382	the existing HBP inhibitors	356:382	However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment.
29515119	3	27	theme	anti-breast	538:548	arg1	effect					557:562	a remarkable anti-breast cancer effect	525:562	a remarkable anti-breast cancer effect	525:562	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	2	28	theme	existing	360:367	arg1	inhibitors					373:382	the existing HBP inhibitors	356:382	the existing HBP inhibitors	356:382	However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment.
29515119	0	29	theme	Hexosamine	18:27	arg1	Pathway					42:48	the Hexosamine Biosynthetic Pathway	14:48	the Hexosamine Biosynthetic Pathway	14:48	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.
29515119	1	30	theme	different	273:281	arg1	roles					283:287	different roles	273:287	different roles	273:287	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	7	31	theme	therapeutic	1262:1272	arg1	purpose					1274:1280	therapeutic purpose	1262:1280	therapeutic purpose	1262:1280	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	2	32	dep	specificity	328:338	arg1	the					320:322	the	320:322	the	320:322	However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment.
29515119	2	33	theme	cancer	408:413	arg1	treatment					415:423	cancer treatment	408:423	cancer treatment	408:423	However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment.
29515119	6	34	theme	Response	1079:1086	arg1	activation					1044:1053	the activation	1040:1053	the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS	1040:1130	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	4	35	dep	cell	644:647	arg1	proliferation					649:661	proliferation	649:661	proliferation	649:661	In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival.
29515119	4	35	dep	cell	644:647	arg1	survival					667:674	survival	667:674	survival	667:674	In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival.
29515119	6	36	theme	accumulation	1098:1109	arg1	activation					1044:1053	the activation	1040:1053	the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS	1040:1130	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	6	37	theme	Unfolded	1062:1069	arg1	Response					1079:1086	the Unfolded Protein Response	1058:1086	the Unfolded Protein Response (UPR)	1058:1092	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	6	37	theme	Unfolded	1062:1069	arg1	UPR					1089:1091	UPR	1089:1091	UPR	1089:1091	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	1	38	theme	augmented	202:210	arg1	flux					212:215	an augmented flux	199:215	an augmented flux through the Hexosamine Biosynthetic Pathway (HBP)	199:265	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	0	39	theme	Pathway	42:48	arg1	Inhibition					0:9	Inhibition	0:9	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3	0:66	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.
29515119	2	40	theme	low	324:326	arg1	specificity					328:338	low specificity	324:338	low specificity	324:338	However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment.
29515119	6	41	theme	impaired	966:973	arg1	survival					975:982	impaired survival	966:982	impaired survival of cancer cells upon FR054 treatment	966:1019	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	4	42	theme	dramatic	623:630	arg1	decrease					632:639	a dramatic decrease	621:639	a dramatic decrease in cell proliferation and survival	621:674	In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival.
29515119	4	43	theme	cancer	608:613	arg1	cells					615:619	different breast cancer cells	591:619	different breast cancer cells	591:619	In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival.
29515119	0	44	theme	Biosynthetic	29:40	arg1	Pathway					42:48	the Hexosamine Biosynthetic Pathway	14:48	the Hexosamine Biosynthetic Pathway	14:48	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.
29515119	1	45	theme	tumor	292:296	arg1	progression					298:308	tumor progression	292:308	tumor progression	292:308	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	1	46	link	O-linked	141:148	arg1	glycosylation					158:170	O-linked protein glycosylation	141:170	O-linked protein glycosylation	141:170	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	7	47	theme	targeting	1244:1252	arg1	HBP					1254:1256	targeting HBP	1244:1256	targeting HBP	1244:1256	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	4	48	theme	breast	601:606	arg1	cells					615:619	different breast cancer cells	591:619	different breast cancer cells	591:619	In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival.
29515119	0	49	theme	targeting	53:61	arg1	PGM3					63:66	targeting PGM3	53:66	targeting PGM3	53:66	Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis.
29515119	3	50	theme	cancer	550:555	arg1	effect					557:562	a remarkable anti-breast cancer effect	525:562	a remarkable anti-breast cancer effect	525:562	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	5	51	theme	N-	841:842	arg1	reduction					823:831	FR054-dependent reduction	807:831	FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration	807:941	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	3	52	with	evaluation	457:466	arg1	effect					557:562	a remarkable anti-breast cancer effect	525:562	a remarkable anti-breast cancer effect	525:562	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	7	53	dep	suppresses	1161:1170	arg1	supporting					1216:1225	supporting	1216:1225	supporting the advantage of targeting HBP for therapeutic purpose	1216:1280	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	7	53	dep	suppresses	1161:1170	arg1	encouraging					1286:1296	encouraging	1286:1296	encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy	1286:1405	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	6	54	theme	cancer	987:992	arg1	cells					994:998	cancer cells	987:998	cancer cells	987:998	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	7	55	theme	further	1298:1304	arg1	investigation					1306:1318	further investigation	1298:1318	further investigation	1298:1318	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	7	56	theme	MDA-MB-231	1189:1198	arg1	mice					1210:1213	MDA-MB-231 xenograft mice	1189:1213	MDA-MB-231 xenograft mice	1189:1213	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	1	57	theme	Cancer	118:123	arg1	N-					134:135	Cancer aberrant N-	118:135	Cancer aberrant N-	118:135	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	5	58	theme	migration	933:941	arg1	reduction					895:903	a strong reduction	886:903	a strong reduction of cancer cell adhesion and migration	886:941	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	7	59	theme	molecule	1348:1355	arg1	use					1330:1332	the use	1326:1332	the use of this small molecule as a promising compound for breast cancer therapy	1326:1405	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	5	60	theme	cell	915:918	arg1	adhesion					920:927	cancer cell adhesion	908:927	cancer cell adhesion	908:927	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	7	61	theme	small	1342:1346	arg1	molecule					1348:1355	this small molecule	1337:1355	this small molecule	1337:1355	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	1	62	theme	aberrant	125:132	arg1	N-					134:135	Cancer aberrant N-	118:135	Cancer aberrant N-	118:135	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	6	63	theme	Protein	1071:1077	arg1	Response					1079:1086	the Unfolded Protein Response	1058:1086	the Unfolded Protein Response (UPR)	1058:1092	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	6	63	theme	Protein	1071:1077	arg1	UPR					1089:1091	UPR	1089:1091	UPR	1089:1091	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	5	64	theme	cancer	908:913	arg1	adhesion					920:927	cancer cell adhesion	908:927	cancer cell adhesion	908:927	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	7	65	theme	xenograft	1200:1208	arg1	mice					1210:1213	MDA-MB-231 xenograft mice	1189:1213	MDA-MB-231 xenograft mice	1189:1213	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	5	66	theme	adhesion	920:927	arg1	reduction					895:903	a strong reduction	886:903	a strong reduction of cancer cell adhesion and migration	886:941	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	3	67	theme	FR054	471:475	arg1	evaluation					457:466	the preclinical evaluation	441:466	the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect	441:562	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	1	68	theme	Hexosamine	229:238	arg1	HBP					262:264	HBP	262:264	HBP	262:264	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	1	68	theme	Hexosamine	229:238	arg1	Pathway					253:259	the Hexosamine Biosynthetic Pathway	225:259	the Hexosamine Biosynthetic Pathway (HBP)	225:265	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	6	69	theme	intracellular	1114:1126	arg1	ROS					1128:1130	intracellular ROS	1114:1130	intracellular ROS	1114:1130	Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS.
29515119	3	70	theme	preclinical	445:455	arg1	evaluation					457:466	the preclinical evaluation	441:466	the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect	441:562	Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect.
29515119	5	71	theme	FR054-dependent	807:821	arg1	reduction					823:831	FR054-dependent reduction	807:831	FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration	807:941	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	7	72	theme	HBP	1254:1256	arg1	advantage					1231:1239	the advantage	1227:1239	the advantage of targeting HBP for therapeutic purpose	1227:1280	Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.
29515119	1	73	theme	Biosynthetic	240:251	arg1	HBP					262:264	HBP	262:264	HBP	262:264	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	1	73	theme	Biosynthetic	240:251	arg1	Pathway					253:259	the Hexosamine Biosynthetic Pathway	225:259	the Hexosamine Biosynthetic Pathway (HBP)	225:265	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
29515119	5	74	theme	Triple	706:711	arg1	TNBC					737:740	TNBC	737:740	TNBC	737:740	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	5	74	theme	Triple	706:711	arg1	Cancer					729:734	Triple Negative Breast Cancer	706:734	Triple Negative Breast Cancer (TNBC) cells	706:747	In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N- and O-glycosylation level that cause also a strong reduction of cancer cell adhesion and migration.
29515119	4	75	theme	different	591:599	arg1	cells					615:619	different breast cancer cells	591:619	different breast cancer cells	591:619	In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival.
29515119	1	76	theme	O-linked	141:148	arg1	glycosylation					158:170	O-linked protein glycosylation	141:170	O-linked protein glycosylation	141:170	Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression.
30384195	1	0	theme	global	276:281	arg1	warming					283:289	global warming	276:289	global warming	276:289	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	12	1	theme	CT448	1741:1745	arg1	modifications					1724:1736	Local evolutionary modifications	1705:1736	Local evolutionary modifications of CT448	1705:1745	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	5	2	with	alignments	747:756	arg1	proteases					776:784	human serine proteases	763:784	human serine proteases	763:784	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	10	3	theme	synthetic	1545:1553	arg1	substrates					1555:1564	various synthetic substrates	1537:1564	various synthetic substrates	1537:1564	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	3	4	from	mechanisms	520:529	arg1	gut					557:559	the gut	553:559	the gut of the crustacean Daphnia magna	553:591	To date, mechanisms of this inhibition in the gut of the crustacean Daphnia magna are not known.
30384195	9	5	theme	protease	1408:1415	arg1	expression					1366:1375	a recombinant expression	1352:1375	a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia	1352:1454	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	3	6	theme	inhibition	539:548	arg1	mechanisms					520:529	mechanisms	520:529	mechanisms of this inhibition in the gut of the crustacean Daphnia magna	520:591	To date, mechanisms of this inhibition in the gut of the crustacean Daphnia magna are not known.
30384195	1	7	theme	toxin-producing	171:185	arg1	cyanobacteria					187:199	toxin-producing cyanobacteria	171:199	toxin-producing cyanobacteria	171:199	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	12	8	theme	Local	1705:1709	arg1	modifications					1724:1736	Local evolutionary modifications	1705:1736	Local evolutionary modifications of CT448	1705:1745	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	4	9	theme	chymotrypsin	656:667	arg1	CT448					674:678	CT448	674:678	CT448	674:678	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	9	theme	chymotrypsin	656:667	arg1	protease					646:653	a single serine protease	630:653	a single serine protease	630:653	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	9	theme	chymotrypsin	656:667	arg1	448					669:671	chymotrypsin 448	656:671	chymotrypsin 448 (CT448)	656:679	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	3	10	theme	crustacean	568:577	arg1	magna					587:591	the crustacean Daphnia magna	564:591	the crustacean Daphnia magna	564:591	To date, mechanisms of this inhibition in the gut of the crustacean Daphnia magna are not known.
30384195	8	11	theme	inactive	1253:1260	arg1	zymogen					1273:1279	The inactive precursor (zymogen)	1249:1280	The inactive precursor (zymogen)	1249:1280	The inactive precursor (zymogen) could be activated by tryptic digestion.
30384195	7	12	theme	3.45 mg/l	1231:1239	arg1	medium					1241:1246	3.45 mg/l medium	1231:1246	3.45 mg/l medium	1231:1246	The protein was purified via a one-step affinity chromatography, which resulted in a protein yield of 3.45 mg/l medium.
30384195	4	13	theme	single	632:637	arg1	protease					646:653	a single serine protease	630:653	a single serine protease	630:653	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	13	theme	single	632:637	arg1	448					669:671	chymotrypsin 448	656:671	chymotrypsin 448 (CT448)	656:679	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	13	theme	single	632:637	arg1	present					691:697	present	691:697	present	691:697	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	9	14	theme	crustacean	1390:1399	arg1	protease					1408:1415	an active crustacean serine protease	1380:1415	an active crustacean serine protease	1380:1415	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	9	15	theme	Daphnia	1448:1454	arg1	gut					1441:1443	the gut	1437:1443	the gut of Daphnia	1437:1454	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	1	16	located	observed	216:223	arg2	developments					155:166	Mass developments	150:166	Mass developments of toxin-producing cyanobacteria	150:199	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	1	16	located	observed	216:223	arg1	ecosystems					239:248	freshwater ecosystems	228:248	freshwater ecosystems due to eutrophication and global warming	228:289	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	3	17	theme	magna	587:591	arg1	gut					557:559	the gut	553:559	the gut of the crustacean Daphnia magna	553:591	To date, mechanisms of this inhibition in the gut of the crustacean Daphnia magna are not known.
30384195	6	18	theme	Sf21	1009:1012	arg1	cells					1021:1025	Sf21 insect cells	1009:1025	Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium	1009:1126	CT448 was heterologously expressed in Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium.
30384195	0	19	theme	protease	63:70	arg1	characterization					28:43	characterization	28:43	characterization	28:43	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	0	19	theme	protease	63:70	arg1	expression					13:22	expression	13:22	expression	13:22	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	2	20	theme	cyanobacteria	496:508	arg1	herbivore					465:473	the major herbivore	455:473	the major herbivore of phytoplankton and cyanobacteria	455:508	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	2	20	theme	cyanobacteria	496:508	arg1	Daphnia					446:452	Daphnia	446:452	Daphnia	446:452	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	0	21	theme	Daphnia	77:83	arg1	magna					85:89	Daphnia magna	77:89	Daphnia magna	77:89	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	4	22	located	present	691:697	arg1	gut					706:708	the gut	702:708	the gut of the crustacean D. magna	702:735	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	22	located	present	691:697	arg2	448					669:671	chymotrypsin 448	656:671	chymotrypsin 448 (CT448)	656:679	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	22	located	present	691:697	arg2	protease					646:653	a single serine protease	630:653	a single serine protease	630:653	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	22	located	present	691:697	arg2	present					691:697	present	691:697	present	691:697	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	23	theme	crustacean	717:726	arg1	magna					731:735	the crustacean D. magna	713:735	the crustacean D. magna	713:735	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	24	theme	magna	731:735	arg1	gut					706:708	the gut	702:708	the gut of the crustacean D. magna	702:735	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	0	25	theme	possible	94:101	arg1	role					103:106	A possible role	92:106	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.	0:148	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	12	26	theme	cyanobacterial	1894:1907	arg1	blooms					1909:1914	cyanobacterial blooms	1894:1914	cyanobacterial blooms	1894:1914	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	0	27	theme	Heterologous	0:11	arg1	expression					13:22	expression	13:22	expression	13:22	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	6	28	theme	expression	1047:1056	arg1	system					1058:1063	a baculovirus expression system	1033:1063	a baculovirus expression system for optimized protein production and secretion into the medium	1033:1126	CT448 was heterologously expressed in Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium.
30384195	2	29	theme	Daphnia	446:452	arg1	proteases					433:441	digestive serine proteases	416:441	digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria	416:508	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	5	30	located	found	964:968	arg2	motifs					952:957	two N-linked glycosylation motifs	925:957	two N-linked glycosylation motifs	925:957	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	5	30	located	found	964:968	arg1	pro-peptide					913:923	this pro-peptide	908:923	this pro-peptide	908:923	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	5	31	theme	N-linked	929:936	arg1	motifs					952:957	two N-linked glycosylation motifs	925:957	two N-linked glycosylation motifs	925:957	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	2	32	theme	phytoplankton	478:490	arg1	herbivore					465:473	the major herbivore	455:473	the major herbivore of phytoplankton and cyanobacteria	455:508	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	2	32	theme	phytoplankton	478:490	arg1	Daphnia					446:452	Daphnia	446:452	Daphnia	446:452	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	10	33	theme	Proteomic	1457:1465	arg1	identification					1467:1480	Proteomic identification	1457:1480	Proteomic identification of protease cleavage sites (PICS)	1457:1514	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	7	34	theme	affinity	1169:1176	arg1	chromatography					1178:1191	a one-step affinity chromatography	1158:1191	a one-step affinity chromatography	1158:1191	The protein was purified via a one-step affinity chromatography, which resulted in a protein yield of 3.45 mg/l medium.
30384195	2	35	theme	digestive	416:424	arg1	proteases					433:441	digestive serine proteases	416:441	digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria	416:508	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	5	36	theme	Sequence	738:745	arg1	alignments					747:756	Sequence alignments	738:756	Sequence alignments with human serine proteases	738:784	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	9	37	theme	first	1335:1339	arg1	example					1341:1347	the first example	1331:1347	the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia	1331:1454	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	9	37	theme	first	1335:1339	arg1	This					1323:1326	This	1323:1326	This	1323:1326	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	12	38	theme	Daphnia	1879:1885	arg1	fitness					1868:1874	the fitness	1864:1874	the fitness of Daphnia	1864:1885	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	12	39	theme	cyanobacterial	1809:1822	arg1	metabolites					1834:1844	cyanobacterial secondary metabolites	1809:1844	cyanobacterial secondary metabolites	1809:1844	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	0	40	theme	novel	50:54	arg1	protease					63:70	a novel serine protease	48:70	a novel serine protease from Daphnia magna	48:89	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	10	41	theme	cleavage	1494:1501	arg1	PICS					1510:1513	PICS	1510:1513	PICS	1510:1513	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	10	41	theme	cleavage	1494:1501	arg1	sites					1503:1507	protease cleavage sites	1485:1507	protease cleavage sites (PICS)	1485:1514	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	9	42	theme	recombinant	1354:1364	arg1	expression					1366:1375	a recombinant expression	1352:1375	a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia	1352:1454	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	11	43	theme	protease	1684:1691	arg1	inhibitors					1693:1702	cyanobacterial protease inhibitors	1669:1702	cyanobacterial protease inhibitors	1669:1702	In this study, we confirm that CT448 is a target of cyanobacterial protease inhibitors.
30384195	5	44	link	N-linked	929:936	arg1	motifs					952:957	two N-linked glycosylation motifs	925:957	two N-linked glycosylation motifs	925:957	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	12	45	theme	susceptible	1789:1799	arg1	enzyme					1777:1782	this proteolytic enzyme	1760:1782	this proteolytic enzyme less susceptible	1760:1799	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	2	46	theme	protease	375:382	arg1	PIs					396:398	PIs	396:398	PIs	396:398	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	2	46	theme	protease	375:382	arg1	inhibitors					384:393	protease inhibitors	375:393	protease inhibitors (PIs)	375:399	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	9	47	theme	active	1383:1388	arg1	protease					1408:1415	an active crustacean serine protease	1380:1415	an active crustacean serine protease	1380:1415	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	6	48	theme	protein	1079:1085	arg1	production					1087:1096	optimized protein production	1069:1096	optimized protein production	1069:1096	CT448 was heterologously expressed in Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium.
30384195	10	49	theme	substrates	1555:1564	arg1	identification					1467:1480	Proteomic identification	1457:1480	Proteomic identification of protease cleavage sites (PICS)	1457:1514	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	10	49	theme	substrates	1555:1564	arg1	hydrolysation					1520:1532	hydrolysation	1520:1532	hydrolysation of various synthetic substrates	1520:1564	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	4	50	attach	present	691:697	arg1	gut					706:708	the gut	702:708	the gut of the crustacean D. magna	702:735	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	50	attach	present	691:697	arg2	448					669:671	chymotrypsin 448	656:671	chymotrypsin 448 (CT448)	656:679	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	50	attach	present	691:697	arg2	protease					646:653	a single serine protease	630:653	a single serine protease	630:653	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	50	attach	present	691:697	arg2	present					691:697	present	691:697	present	691:697	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	9	51	theme	serine	1401:1406	arg1	protease					1408:1415	an active crustacean serine protease	1380:1415	an active crustacean serine protease	1380:1415	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	10	52	theme	various	1537:1543	arg1	substrates					1555:1564	various synthetic substrates	1537:1564	various synthetic substrates	1537:1564	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	2	53	theme	mass	298:301	arg1	developments					303:314	These mass developments	292:314	These mass developments	292:314	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	5	54	theme	N-terminal	821:830	arg1	pro-peptide					832:842	a putative N-terminal pro-peptide	810:842	a putative N-terminal pro-peptide which is extended compared to the mammalian homologs	810:895	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	12	55	theme	evolutionary	1711:1722	arg1	modifications					1724:1736	Local evolutionary modifications	1705:1736	Local evolutionary modifications of CT448	1705:1745	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	4	56	theme	serine	639:644	arg1	protease					646:653	a single serine protease	630:653	a single serine protease	630:653	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	56	theme	serine	639:644	arg1	448					669:671	chymotrypsin 448	656:671	chymotrypsin 448 (CT448)	656:679	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	56	theme	serine	639:644	arg1	present					691:697	present	691:697	present	691:697	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	1	57	theme	cyanobacteria	187:199	arg1	developments					155:166	Mass developments	150:166	Mass developments of toxin-producing cyanobacteria	150:199	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	0	58	from	magna	85:89	arg1	protease					63:70	a novel serine protease	48:70	a novel serine protease from Daphnia magna	48:89	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	0	58	from	magna	85:89	arg1	characterization					28:43	characterization	28:43	characterization	28:43	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	0	58	from	magna	85:89	arg1	expression					13:22	expression	13:22	expression	13:22	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	0	59	theme	toxic	129:133	arg1	cyanobacteria					135:147	toxic cyanobacteria	129:147	toxic cyanobacteria	129:147	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	8	60	theme	precursor	1262:1270	arg1	zymogen					1273:1279	The inactive precursor (zymogen)	1249:1280	The inactive precursor (zymogen)	1249:1280	The inactive precursor (zymogen) could be activated by tryptic digestion.
30384195	10	61	theme	chymotrypsin-like	1589:1605	arg1	CT448					1578:1582	CT448	1578:1582	CT448	1578:1582	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	10	61	theme	chymotrypsin-like	1589:1605	arg1	elastase					1607:1614	a chymotrypsin-like elastase	1587:1614	a chymotrypsin-like elastase	1587:1614	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	3	62	theme	Daphnia	579:585	arg1	magna					587:591	the crustacean Daphnia magna	564:591	the crustacean Daphnia magna	564:591	To date, mechanisms of this inhibition in the gut of the crustacean Daphnia magna are not known.
30384195	5	63	theme	mammalian	878:886	arg1	homologs					888:895	the mammalian homologs	874:895	the mammalian homologs	874:895	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	0	64	from	role	103:106	arg1	susceptibility					111:124	susceptibility	111:124	susceptibility to toxic cyanobacteria	111:147	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	6	65	theme	insect	1014:1019	arg1	cells					1021:1025	Sf21 insect cells	1009:1025	Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium	1009:1126	CT448 was heterologously expressed in Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium.
30384195	7	66	theme	protein	1214:1220	arg1	yield					1222:1226	a protein yield	1212:1226	a protein yield of 3.45 mg/l medium	1212:1246	The protein was purified via a one-step affinity chromatography, which resulted in a protein yield of 3.45 mg/l medium.
30384195	5	67	gly	glycosylation	938:950	arg2	motifs					952:957	two N-linked glycosylation motifs	925:957	two N-linked glycosylation motifs	925:957	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	0	68	from	characterization	28:43	arg1	magna					85:89	Daphnia magna	77:89	Daphnia magna	77:89	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	1	69	theme	Mass	150:153	arg1	developments					155:166	Mass developments	150:166	Mass developments of toxin-producing cyanobacteria	150:199	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	0	70	from	expression	13:22	arg1	magna					85:89	Daphnia magna	77:89	Daphnia magna	77:89	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	8	71	theme	tryptic	1304:1310	arg1	digestion					1312:1320	tryptic digestion	1304:1320	tryptic digestion	1304:1320	The inactive precursor (zymogen) could be activated by tryptic digestion.
30384195	5	72	theme	glycosylation	938:950	arg1	motifs					952:957	two N-linked glycosylation motifs	925:957	two N-linked glycosylation motifs	925:957	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	6	73	theme	optimized	1069:1077	arg1	production					1087:1096	optimized protein production	1069:1096	optimized protein production	1069:1096	CT448 was heterologously expressed in Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium.
30384195	4	74	theme	D.	728:729	arg1	magna					731:735	the crustacean D. magna	713:735	the crustacean D. magna	713:735	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	5	75	theme	human	763:767	arg1	proteases					776:784	human serine proteases	763:784	human serine proteases	763:784	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	4	76	from	gut	706:708	arg1	protease					646:653	a single serine protease	630:653	a single serine protease	630:653	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	4	76	from	gut	706:708	arg1	present					691:697	present	691:697	present	691:697	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	5	77	theme	serine	769:774	arg1	proteases					776:784	human serine proteases	763:784	human serine proteases	763:784	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	6	78	theme	baculovirus	1035:1045	arg1	system					1058:1063	a baculovirus expression system	1033:1063	a baculovirus expression system for optimized protein production and secretion into the medium	1033:1126	CT448 was heterologously expressed in Sf21 insect cells using a baculovirus expression system for optimized protein production and secretion into the medium.
30384195	2	79	theme	serine	426:431	arg1	proteases					433:441	digestive serine proteases	416:441	digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria	416:508	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	5	80	theme	putative	812:819	arg1	pro-peptide					832:842	a putative N-terminal pro-peptide	810:842	a putative N-terminal pro-peptide which is extended compared to the mammalian homologs	810:895	Sequence alignments with human serine proteases revealed that CT448 has a putative N-terminal pro-peptide which is extended compared to the mammalian homologs and within this pro-peptide two N-linked glycosylation motifs were found.
30384195	1	81	theme	due	250:252	arg1	ecosystems					239:248	freshwater ecosystems	228:248	freshwater ecosystems due to eutrophication and global warming	228:289	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	0	82	theme	serine	56:61	arg1	protease					63:70	a novel serine protease	48:70	a novel serine protease from Daphnia magna	48:89	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	2	83	theme	major	459:463	arg1	herbivore					465:473	the major herbivore	455:473	the major herbivore of phytoplankton and cyanobacteria	455:508	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	2	83	theme	major	459:463	arg1	Daphnia					446:452	Daphnia	446:452	Daphnia	446:452	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	10	84	theme	sites	1503:1507	arg1	identification					1467:1480	Proteomic identification	1457:1480	Proteomic identification of protease cleavage sites (PICS)	1457:1514	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	10	84	theme	sites	1503:1507	arg1	hydrolysation					1520:1532	hydrolysation	1520:1532	hydrolysation of various synthetic substrates	1520:1564	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	11	85	theme	inhibitors	1693:1702	arg1	target					1659:1664	a target	1657:1664	a target of cyanobacterial protease inhibitors	1657:1702	In this study, we confirm that CT448 is a target of cyanobacterial protease inhibitors.
30384195	11	85	theme	inhibitors	1693:1702	arg1	CT448					1648:1652	CT448	1648:1652	CT448	1648:1652	In this study, we confirm that CT448 is a target of cyanobacterial protease inhibitors.
30384195	4	86	from	present	691:697	arg1	gut					706:708	the gut	702:708	the gut of the crustacean D. magna	702:735	Here, we characterize a single serine protease, chymotrypsin 448 (CT448), which is present in the gut of the crustacean D. magna.
30384195	12	87	theme	secondary	1824:1832	arg1	metabolites					1834:1844	cyanobacterial secondary metabolites	1809:1844	cyanobacterial secondary metabolites	1809:1844	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	10	88	theme	protease	1485:1492	arg1	PICS					1510:1513	PICS	1510:1513	PICS	1510:1513	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	10	88	theme	protease	1485:1492	arg1	sites					1503:1507	protease cleavage sites	1485:1507	protease cleavage sites (PICS)	1485:1514	Proteomic identification of protease cleavage sites (PICS) and hydrolysation of various synthetic substrates showed that CT448 is a chymotrypsin-like elastase.
30384195	11	89	theme	cyanobacterial	1669:1682	arg1	inhibitors					1693:1702	cyanobacterial protease inhibitors	1669:1702	cyanobacterial protease inhibitors	1669:1702	In this study, we confirm that CT448 is a target of cyanobacterial protease inhibitors.
30384195	2	90	theme	cyanobacterial	344:357	arg1	inhibitors					384:393	protease inhibitors	375:393	protease inhibitors (PIs)	375:399	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	2	90	theme	cyanobacterial	344:357	arg1	toxins					359:364	cyanobacterial toxins	344:364	cyanobacterial toxins	344:364	These mass developments can partly be attributed to cyanobacterial toxins, such as protease inhibitors (PIs), which inhibit digestive serine proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria.
30384195	9	91	theme	expression	1366:1375	arg1	example					1341:1347	the first example	1331:1347	the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia	1331:1454	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	9	91	theme	expression	1366:1375	arg1	This					1323:1326	This	1323:1326	This	1323:1326	This is the first example of a recombinant expression of an active crustacean serine protease, which functions in the gut of Daphnia.
30384195	1	92	theme	freshwater	228:237	arg1	ecosystems					239:248	freshwater ecosystems	228:248	freshwater ecosystems due to eutrophication and global warming	228:289	Mass developments of toxin-producing cyanobacteria are frequently observed in freshwater ecosystems due to eutrophication and global warming.
30384195	0	93	dep	expression	13:22	arg1	role					103:106	A possible role	92:106	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.	0:148	Heterologous expression and characterization of a novel serine protease from Daphnia magna: A possible role in susceptibility to toxic cyanobacteria.
30384195	12	94	theme	proteolytic	1765:1775	arg1	enzyme					1777:1782	this proteolytic enzyme	1760:1782	this proteolytic enzyme less susceptible	1760:1799	Local evolutionary modifications of CT448 might render this proteolytic enzyme less susceptible against cyanobacterial secondary metabolites and might improve the fitness of Daphnia during cyanobacterial blooms.
30384195	7	95	theme	medium	1241:1246	arg1	yield					1222:1226	a protein yield	1212:1226	a protein yield of 3.45 mg/l medium	1212:1246	The protein was purified via a one-step affinity chromatography, which resulted in a protein yield of 3.45 mg/l medium.
30384195	7	96	theme	one-step	1160:1167	arg1	chromatography					1178:1191	a one-step affinity chromatography	1158:1191	a one-step affinity chromatography	1158:1191	The protein was purified via a one-step affinity chromatography, which resulted in a protein yield of 3.45 mg/l medium.
29983388	0	0	theme	Core	72:75	arg1	Fucosylations					77:89	Core Fucosylations	72:89	Core Fucosylations	72:89	FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
29983388	4	1	theme	Silencing	676:684	arg1	FUT8					686:689	Silencing FUT8	676:689	Silencing FUT8	676:689	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	2	2	link	N-linked	473:480	arg1	glycans					482:488	N-linked glycans	473:488	N-linked glycans of membrane-associated proteins, including several integrin subunits	473:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	1	3	theme	trials	145:150	arg1	hundreds					124:131	hundreds	124:131	hundreds of clinical trials	124:150	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	5	4	from	glycans	932:938	arg1	position					954:961	a specific position	943:961	a specific position	943:961	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	2	5	theme	proteins	513:520	arg1	glycans					482:488	N-linked glycans	473:488	N-linked glycans of membrane-associated proteins, including several integrin subunits	473:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	7	6	from	delivery	1087:1094	arg1	settings					1119:1126	therapeutic settings	1107:1126	therapeutic settings	1107:1126	This work may help improve delivery of MSCs in therapeutic settings.
29983388	5	7	from	degrees	857:863	arg1	surface					905:911	the integrin's surface	890:911	the integrin's surface	890:911	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	6	8	theme	MSCs	1031:1034	arg1	migration					1018:1026	migration	1018:1026	migration of MSCs	1018:1034	Altogether, we show a mechanism whereby FGF2 promotes migration of MSCs by modifying N-glycans.
29983388	2	9	theme	glycans	482:488	arg1	fucosylations					456:468	core fucosylations	451:468	core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits	451:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	3	10	theme	MSCs	670:673	arg1	migration					657:665	migration	657:665	migration of MSCs	657:673	Gain- and loss-of-function experiments show that FUT8 is both necessary and sufficient to induce migration of MSCs.
29983388	1	11	theme	effective	240:248	arg1	delivery					250:257	effective delivery	240:257	effective delivery of the cells to target tissues	240:288	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	2	12	theme	N-linked	473:480	arg1	glycans					482:488	N-linked glycans	473:488	N-linked glycans of membrane-associated proteins, including several integrin subunits	473:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	13	theme	unexplored	320:329	arg1	mechanism					331:339	an unexplored mechanism	317:339	an unexplored mechanism	317:339	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	14	dep	induces	389:395	arg1	FUT8					433:436	FUT8	433:436	FUT8	433:436	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	15	gly	fucosylations	456:468	arg1	glycans					482:488	N-linked glycans	473:488	N-linked glycans of membrane-associated proteins, including several integrin subunits	473:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	16	theme	fibroblast	357:366	arg1	factor					375:380	basic fibroblast growth factor	351:380	basic fibroblast growth factor (FGF2)	351:387	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	16	theme	fibroblast	357:366	arg1	FGF2					383:386	FGF2	383:386	FGF2	383:386	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	17	theme	fucosyltransferase	411:428	arg1	expression					397:406	expression	397:406	expression of fucosyltransferase 8	397:430	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	5	18	theme	in	793:794	arg1	modeling					803:810	in silico modeling	793:810	in silico modeling	793:810	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	2	19	theme	basic	351:355	arg1	factor					375:380	basic fibroblast growth factor	351:380	basic fibroblast growth factor (FGF2)	351:387	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	19	theme	basic	351:355	arg1	FGF2					383:386	FGF2	383:386	FGF2	383:386	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	7	20	theme	therapeutic	1107:1117	arg1	settings					1119:1126	therapeutic settings	1107:1126	therapeutic settings	1107:1126	This work may help improve delivery of MSCs in therapeutic settings.
29983388	4	21	theme	MSCs	717:720	arg1	model					770:774	a murine bone fracture model	747:774	a murine bone fracture model	747:774	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	4	21	theme	MSCs	717:720	arg1	migration					704:712	migration	704:712	migration of MSCs in zebrafish embryos	704:741	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	5	22	theme	core	825:828	arg1	fucosylations					830:842	core fucosylations	825:842	core fucosylations	825:842	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	7	23	theme	MSCs	1099:1102	arg1	delivery					1087:1094	delivery	1087:1094	delivery of MSCs in therapeutic settings	1087:1126	This work may help improve delivery of MSCs in therapeutic settings.
29983388	5	24	dep	in	793:794	arg1	silico					796:801	silico	796:801	silico	796:801	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	4	25	theme	zebrafish	725:733	arg1	embryos					735:741	zebrafish embryos	725:741	zebrafish embryos	725:741	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	1	26	theme	multipotent	181:191	arg1	MSCs					208:211	MSCs	208:211	MSCs	208:211	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	1	26	theme	multipotent	181:191	arg1	cells					201:205	multipotent stromal cells	181:205	multipotent stromal cells (MSCs)	181:212	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	1	27	theme	cells	266:270	arg1	delivery					250:257	effective delivery	240:257	effective delivery of the cells to target tissues	240:288	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	0	28	theme	Integrins	107:115	arg1	N-Glycans					94:102	N-Glycans	94:102	N-Glycans of Integrins	94:115	FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
29983388	1	29	theme	stromal	193:199	arg1	MSCs					208:211	MSCs	208:211	MSCs	208:211	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	1	29	theme	stromal	193:199	arg1	cells					201:205	multipotent stromal cells	181:205	multipotent stromal cells (MSCs)	181:212	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	0	30	theme	Bone	32:35	arg1	Cells					52:56	Human Bone Marrow Stromal Cells	26:56	Human Bone Marrow Stromal Cells	26:56	FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
29983388	2	31	theme	membrane-associated	493:511	arg1	proteins					513:520	membrane-associated proteins	493:520	membrane-associated proteins	493:520	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	31	theme	membrane-associated	493:511	arg1	subunits					550:557	several integrin subunits	533:557	several integrin subunits	533:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	1	32	theme	cells	201:205	arg1	use					174:176	the use	170:176	the use of multipotent stromal cells (MSCs) for therapeutic purposes	170:237	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	0	33	theme	Human	26:30	arg1	Cells					52:56	Human Bone Marrow Stromal Cells	26:56	Human Bone Marrow Stromal Cells	26:56	FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
29983388	1	34	theme	target	275:280	arg1	tissues					282:288	target tissues	275:288	target tissues	275:288	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	2	35	theme	growth	368:373	arg1	factor					375:380	basic fibroblast growth factor	351:380	basic fibroblast growth factor (FGF2)	351:387	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	2	35	theme	growth	368:373	arg1	FGF2					383:386	FGF2	383:386	FGF2	383:386	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	0	36	theme	Stromal	44:50	arg1	Cells					52:56	Human Bone Marrow Stromal Cells	26:56	Human Bone Marrow Stromal Cells	26:56	FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
29983388	5	37	theme	freedom	868:874	arg1	degrees					857:863	the degrees	853:863	the degrees of freedom of glycans on the integrin's surface	853:911	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	0	38	theme	Marrow	37:42	arg1	Cells					52:56	Human Bone Marrow Stromal Cells	26:56	Human Bone Marrow Stromal Cells	26:56	FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
29983388	2	39	theme	integrin	541:548	arg1	subunits					550:557	several integrin subunits	533:557	several integrin subunits	533:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	4	40	from	migration	704:712	arg1	embryos					735:741	zebrafish embryos	725:741	zebrafish embryos	725:741	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	2	41	theme	several	533:539	arg1	subunits					550:557	several integrin subunits	533:557	several integrin subunits	533:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	4	42	theme	fracture	761:768	arg1	model					770:774	a murine bone fracture model	747:774	a murine bone fracture model	747:774	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	5	43	theme	glycans	879:885	arg1	freedom					868:874	freedom	868:874	freedom of glycans	868:885	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	4	44	theme	murine	749:754	arg1	model					770:774	a murine bone fracture model	747:774	a murine bone fracture model	747:774	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	4	45	theme	bone	756:759	arg1	model					770:774	a murine bone fracture model	747:774	a murine bone fracture model	747:774	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	2	46	theme	core	451:454	arg1	fucosylations					456:468	core fucosylations	451:468	core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits	451:557	We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylations of N-linked glycans of membrane-associated proteins, including several integrin subunits.
29983388	5	47	theme	specific	945:952	arg1	position					954:961	a specific position	943:961	a specific position	943:961	Finally, we use in silico modeling to show that core fucosylations restrict the degrees of freedom of glycans on the integrin's surface, hence stabilizing glycans on a specific position.
29983388	4	48	from	model	770:774	arg1	embryos					735:741	zebrafish embryos	725:741	zebrafish embryos	725:741	Silencing FUT8 also affects migration of MSCs in zebrafish embryos and a murine bone fracture model.
29983388	3	49	dep	Gain-	560:564	arg1	experiments					587:597	experiments	587:597	experiments	587:597	Gain- and loss-of-function experiments show that FUT8 is both necessary and sufficient to induce migration of MSCs.
29983388	0	50	theme	Cells	52:56	arg1	Migration					13:21	Migration	13:21	Migration of Human Bone Marrow Stromal Cells	13:56	FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins.
29983388	1	51	theme	clinical	136:143	arg1	trials					145:150	clinical trials	136:150	clinical trials	136:150	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29983388	1	52	theme	therapeutic	218:228	arg1	purposes					230:237	therapeutic purposes	218:237	therapeutic purposes	218:237	Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical.
29336543	1	0	theme	HDAC	115:118	arg1	subfamily					120:128	the class IV HDAC subfamily	102:128	the class IV HDAC subfamily	102:128	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	4	1	theme	Catalytic	530:538	arg1	efficiencies					540:551	Catalytic efficiencies	530:551	Catalytic efficiencies toward dodecanoylated and myristoylated peptides	530:600	Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient fatty-acid deacylase of the HDAC family.
29336543	2	2	theme	acyl	315:318	arg1	moieties					320:327	acyl moieties	315:327	acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate	315:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	7	3	theme	additional	1194:1203	arg1	functions					1216:1224	additional biological functions	1194:1224	additional biological functions of the enzyme	1194:1238	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	7	4	theme	HDAC11	1139:1144	arg1	activity					1127:1134	novel enzymatic activity	1111:1134	novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors	1111:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	7	5	theme	inhibitors	1287:1296	arg1	uncovering					1180:1189	the uncovering	1176:1189	the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors	1176:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	7	5	theme	inhibitors	1287:1296	arg1	design					1255:1260	the design	1251:1260	the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors	1176:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	1	6	theme	Histone	50:56	arg1	deacetylase					58:68	Histone deacetylase 11	50:71	Histone deacetylase 11 (HDAC11)	50:80	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	1	6	theme	Histone	50:56	arg1	HDAC11					74:79	HDAC11	74:79	HDAC11	74:79	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	1	6	theme	Histone	50:56	arg1	member					92:97	a sole member	85:97	a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity	85:177	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	4	7	theme	HDAC	711:714	arg1	family					716:721	the HDAC family	707:721	the HDAC family	707:721	Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient fatty-acid deacylase of the HDAC family.
29336543	6	8	theme	metabolic	1024:1032	arg1	control					1034:1040	metabolic control	1024:1040	metabolic control of the enzymatic activity by fatty-acid metabolites	1024:1092	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	4	9	theme	fatty-acid	683:692	arg1	deacylase					694:702	the most proficient fatty-acid deacylase	663:702	the most proficient fatty-acid deacylase of the HDAC family	663:721	Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient fatty-acid deacylase of the HDAC family.
29336543	3	10	theme	lipoic	450:455	arg1	acid					457:460	N-linked lipoic acid	441:460	N-linked lipoic acid	441:460	Additionally, N-linked lipoic acid and biotin are removed by the enzyme, although with lower efficacy.
29336543	2	11	theme	side	360:363	arg1	nitrogen					371:378	the side chain nitrogen	356:378	the side chain nitrogen of the lysine residue of a peptidic substrate	356:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	6	12	theme	deacylase	901:909	arg1	activity					911:918	its deacylase activity	897:918	its deacylase activity	897:918	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	6	13	theme	enzymatic	1049:1057	arg1	activity					1059:1066	the enzymatic activity	1045:1066	the enzymatic activity	1045:1066	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	2	14	theme	activities	235:244	arg1	profiling					205:213	in vitro profiling	196:213	in vitro profiling of HDAC11 deacylase activities	196:244	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	1	15	theme	negligible	135:144	arg1	activity					170:177	negligible intrinsic deacetylation activity	135:177	negligible intrinsic deacetylation activity	135:177	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	5	16	theme	free	771:774	arg1	acids					808:812	free myristic, palmitic, and stearic acids	771:812	free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM	771:862	Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM, respectively.
29336543	3	17	theme	lower	514:518	arg1	efficacy					520:527	lower efficacy	514:527	lower efficacy	514:527	Additionally, N-linked lipoic acid and biotin are removed by the enzyme, although with lower efficacy.
29336543	7	18	theme	novel	1111:1115	arg1	activity					1127:1134	novel enzymatic activity	1111:1134	novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors	1111:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	1	19	theme	intrinsic	146:154	arg1	activity					170:177	negligible intrinsic deacetylation activity	135:177	negligible intrinsic deacetylation activity	135:177	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	0	20	theme	Histone	0:6	arg1	Deacylase					39:47	a Fatty-Acid Deacylase	26:47	a Fatty-Acid Deacylase	26:47	Histone Deacetylase 11 Is a Fatty-Acid Deacylase.
29336543	0	20	theme	Histone	0:6	arg1	Deacetylase					8:18	Histone Deacetylase 11	0:21	Histone Deacetylase 11	0:21	Histone Deacetylase 11 Is a Fatty-Acid Deacylase.
29336543	1	21	with	member	92:97	arg1	activity					170:177	negligible intrinsic deacetylation activity	135:177	negligible intrinsic deacetylation activity	135:177	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	1	22	theme	deacetylation	156:168	arg1	activity					170:177	negligible intrinsic deacetylation activity	135:177	negligible intrinsic deacetylation activity	135:177	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	2	23	theme	residue	394:400	arg1	nitrogen					371:378	the side chain nitrogen	356:378	the side chain nitrogen of the lysine residue of a peptidic substrate	356:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	5	24	theme	myristic	776:783	arg1	acids					808:812	free myristic, palmitic, and stearic acids	771:812	free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM	771:862	Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM, respectively.
29336543	4	25	theme	family	716:721	arg1	deacylase					694:702	the most proficient fatty-acid deacylase	663:702	the most proficient fatty-acid deacylase of the HDAC family	663:721	Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient fatty-acid deacylase of the HDAC family.
29336543	7	26	theme	enzyme	1233:1238	arg1	functions					1216:1224	additional biological functions	1194:1224	additional biological functions of the enzyme	1194:1238	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	2	27	theme	lysine	387:392	arg1	substrate					416:424	a peptidic substrate	405:424	a peptidic substrate	405:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	2	27	theme	lysine	387:392	arg1	residue					394:400	the lysine residue	383:400	the lysine residue of a peptidic substrate	383:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	5	28	with	acids	808:812	arg1	constants					830:838	inhibition constants	819:838	inhibition constants of 6.5, 0.9, and 1.6 μM	819:862	Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM, respectively.
29336543	1	29	theme	subfamily	120:128	arg1	member					92:97	a sole member	85:97	a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity	85:177	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	1	29	theme	subfamily	120:128	arg1	deacetylase					58:68	Histone deacetylase 11	50:71	Histone deacetylase 11 (HDAC11)	50:80	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	1	30	theme	class	106:110	arg1	subfamily					120:128	the class IV HDAC subfamily	102:128	the class IV HDAC subfamily	102:128	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	0	31	theme	Fatty-Acid	28:37	arg1	Deacylase					39:47	a Fatty-Acid Deacylase	26:47	a Fatty-Acid Deacylase	26:47	Histone Deacetylase 11 Is a Fatty-Acid Deacylase.
29336543	0	31	theme	Fatty-Acid	28:37	arg1	Deacetylase					8:18	Histone Deacetylase 11	0:21	Histone Deacetylase 11	0:21	Histone Deacetylase 11 Is a Fatty-Acid Deacylase.
29336543	6	32	theme	same	886:889	arg1	time					891:894	the same time	882:894	the same time	882:894	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	6	33	theme	palmitoyl-coenzyme	961:978	arg1	A					980:980	palmitoyl-coenzyme A	961:980	palmitoyl-coenzyme A	961:980	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	6	34	theme	myristoyl-coenzyme	986:1003	arg1	A					1005:1005	myristoyl-coenzyme A	986:1005	myristoyl-coenzyme A	986:1005	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	5	35	theme	stearic	800:806	arg1	acids					808:812	free myristic, palmitic, and stearic acids	771:812	free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM	771:862	Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM, respectively.
29336543	2	36	theme	in	196:197	arg1	profiling					205:213	in vitro profiling	196:213	in vitro profiling of HDAC11 deacylase activities	196:244	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	2	37	theme	chain	365:369	arg1	nitrogen					371:378	the side chain nitrogen	356:378	the side chain nitrogen of the lysine residue of a peptidic substrate	356:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	2	38	theme	substrate	416:424	arg1	substrate					416:424	a peptidic substrate	405:424	a peptidic substrate	405:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	2	38	theme	substrate	416:424	arg1	residue					394:400	the lysine residue	383:400	the lysine residue of a peptidic substrate	383:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	1	39	theme	sole	87:90	arg1	member					92:97	a sole member	85:97	a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity	85:177	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	1	39	theme	sole	87:90	arg1	deacetylase					58:68	Histone deacetylase 11	50:71	Histone deacetylase 11 (HDAC11)	50:80	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	2	40	theme	peptidic	407:414	arg1	substrate					416:424	a peptidic substrate	405:424	a peptidic substrate	405:424	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	3	41	link	N-linked	441:448	arg1	acid					457:460	N-linked lipoic acid	441:460	N-linked lipoic acid	441:460	Additionally, N-linked lipoic acid and biotin are removed by the enzyme, although with lower efficacy.
29336543	7	42	theme	biological	1205:1214	arg1	functions					1216:1224	additional biological functions	1194:1224	additional biological functions of the enzyme	1194:1238	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	6	43	theme	activity	1059:1066	arg1	control					1034:1040	metabolic control	1024:1040	metabolic control of the enzymatic activity by fatty-acid metabolites	1024:1092	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	7	44	theme	isoform-specific	1265:1280	arg1	inhibitors					1287:1296	isoform-specific HDAC inhibitors	1265:1296	isoform-specific HDAC inhibitors	1265:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	4	45	theme	proficient	672:681	arg1	deacylase					694:702	the most proficient fatty-acid deacylase	663:702	the most proficient fatty-acid deacylase of the HDAC family	663:721	Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient fatty-acid deacylase of the HDAC family.
29336543	7	46	theme	HDAC	1282:1285	arg1	inhibitors					1287:1296	isoform-specific HDAC inhibitors	1265:1296	isoform-specific HDAC inhibitors	1265:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	2	47	theme	deacylase	225:233	arg1	activities					235:244	HDAC11 deacylase activities	218:244	HDAC11 deacylase activities	218:244	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	5	48	theme	μM	861:862	arg1	constants					830:838	inhibition constants	819:838	inhibition constants of 6.5, 0.9, and 1.6 μM	819:862	Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM, respectively.
29336543	7	49	theme	functions	1216:1224	arg1	uncovering					1180:1189	the uncovering	1176:1189	the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors	1176:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	7	49	theme	functions	1216:1224	arg1	design					1255:1260	the design	1251:1260	the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors	1176:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	2	50	theme	HDAC11	218:223	arg1	activities					235:244	HDAC11 deacylase activities	218:244	HDAC11 deacylase activities	218:244	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	3	51	theme	N-linked	441:448	arg1	acid					457:460	N-linked lipoic acid	441:460	N-linked lipoic acid	441:460	Additionally, N-linked lipoic acid and biotin are removed by the enzyme, although with lower efficacy.
29336543	4	52	theme	dodecanoylated	560:573	arg1	peptides					593:600	dodecanoylated and myristoylated peptides	560:600	dodecanoylated and myristoylated peptides	560:600	Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient fatty-acid deacylase of the HDAC family.
29336543	2	53	dep	in	196:197	arg1	vitro					199:203	vitro	199:203	vitro	199:203	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	2	54	theme	8-18	338:341	arg1	carbons					343:349	8-18 carbons	338:349	8-18 carbons	338:349	Here, we report in vitro profiling of HDAC11 deacylase activities, and our data unequivocally show that the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side chain nitrogen of the lysine residue of a peptidic substrate.
29336543	5	55	theme	inhibition	819:828	arg1	constants					830:838	inhibition constants	819:838	inhibition constants of 6.5, 0.9, and 1.6 μM	819:862	Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM, respectively.
29336543	6	56	theme	fatty-acid	1071:1080	arg1	metabolites					1082:1092	fatty-acid metabolites	1071:1092	fatty-acid metabolites	1071:1092	At the same time, its deacylase activity is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl-coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty-acid metabolites.
29336543	5	57	theme	palmitic	786:793	arg1	acids					808:812	free myristic, palmitic, and stearic acids	771:812	free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM	771:862	Interestingly, HDAC11 is strongly inhibited by free myristic, palmitic, and stearic acids with inhibition constants of 6.5, 0.9, and 1.6 μM, respectively.
29336543	1	58	theme	IV	112:113	arg1	subfamily					120:128	the class IV HDAC subfamily	102:128	the class IV HDAC subfamily	102:128	Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily with negligible intrinsic deacetylation activity.
29336543	7	59	theme	enzymatic	1117:1125	arg1	activity					1127:1134	novel enzymatic activity	1111:1134	novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors	1111:1296	Our data reveal novel enzymatic activity of HDAC11 that can, in turn, facilitate the uncovering of additional biological functions of the enzyme as well as the design of isoform-specific HDAC inhibitors.
29336543	4	60	theme	myristoylated	579:591	arg1	peptides					593:600	dodecanoylated and myristoylated peptides	560:600	dodecanoylated and myristoylated peptides	560:600	Catalytic efficiencies toward dodecanoylated and myristoylated peptides were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient fatty-acid deacylase of the HDAC family.
31702909	7	0	theme	CD19	1224:1227	arg1	variant					1229:1235	additional CD19 variant design and analysis	1213:1255	additional CD19 variant design and analysis	1213:1255	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	3	1	theme	single-site	507:517	arg1	library					539:545	a comprehensive single-site saturation mutation library	491:545	a comprehensive single-site saturation mutation library of the human CD19 extracellular domain	491:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	4	2	theme	published	891:899	arg1	epitope					901:907	the published epitope	887:907	the published epitope of antibody B43	887:923	All three antibodies had partially overlapping, yet distinct, epitopes near the published epitope of antibody B43.
31702909	9	3	theme	affinity-stability	1595:1612	arg1	trade-offs					1614:1623	evolutionary affinity-stability trade-offs	1582:1623	evolutionary affinity-stability trade-offs	1582:1623	Screening for thermally stable variants identified mutations to guide further CD19 stabilization for fusion protein applications and revealed evolutionary affinity-stability trade-offs.
31702909	3	4	theme	human	554:558	arg1	domain					579:584	the human CD19 extracellular domain	550:584	the human CD19 extracellular domain	550:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	1	5	theme	immune	246:251	arg1	therapy					258:264	immune cell therapy	246:264	immune cell therapy	246:264	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	0	6	theme	Fine	0:3	arg1	Mapping					13:19	Fine Epitope Mapping	0:19	Fine Epitope Mapping of the CD19 Extracellular Domain	0:52	Fine Epitope Mapping of the CD19 Extracellular Domain Promotes Design.
31702909	8	7	link	N-linked	1291:1298	arg1	sites					1314:1318	all N-linked glycosylation sites	1287:1318	all N-linked glycosylation sites removed successfully	1287:1339	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	3	8	theme	various	763:769	arg1	types					771:775	various types	763:775	various types of CD19 research and development	763:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	7	9	dep	variant	1229:1235	arg1	design					1237:1242	design	1237:1242	design	1237:1242	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	7	9	dep	variant	1229:1235	arg1	analysis					1248:1255	analysis	1248:1255	analysis	1248:1255	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	3	10	theme	extracellular	565:577	arg1	domain					579:584	the human CD19 extracellular domain	550:584	the human CD19 extracellular domain	550:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	3	11	used	used	755:758	arg2	3B10					733:736	3B10	733:736	3B10	733:736	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	3	11	used	used	755:758	arg2	4G7-2E3					721:727	4G7-2E3	721:727	4G7-2E3	721:727	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	8	12	theme	designed	1260:1267	arg1	variant					1274:1280	A designed CD19 variant	1258:1280	A designed CD19 variant with all N-linked glycosylation sites removed successfully	1258:1339	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	3	13	theme	research	785:792	arg1	types					771:775	various types	763:775	various types of CD19 research and development	763:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	10	14	theme	sequence-function	1663:1679	arg1	relationships					1681:1693	CD19 sequence-function relationships	1658:1693	CD19 sequence-function relationships	1658:1693	These fundamental insights into CD19 sequence-function relationships enhance our understanding of antibody-mediated CD19-targeted therapeutics.
31702909	4	15	theme	B43	921:923	arg1	epitope					901:907	the published epitope	887:907	the published epitope of antibody B43	887:923	All three antibodies had partially overlapping, yet distinct, epitopes near the published epitope of antibody B43.
31702909	3	16	theme	CD19	650:653	arg1	antibody					655:662	binding FMC63-the dominant CD19 antibody	623:662	binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development	623:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	9	17	theme	CD19	1518:1521	arg1	stabilization					1523:1535	further CD19 stabilization	1510:1535	further CD19 stabilization for fusion protein applications	1510:1567	Screening for thermally stable variants identified mutations to guide further CD19 stabilization for fusion protein applications and revealed evolutionary affinity-stability trade-offs.
31702909	5	18	theme	FMC63	930:934	arg1	epitope					951:957	The FMC63 conformational epitope	926:957	The FMC63 conformational epitope	926:957	The FMC63 conformational epitope spans spatially adjacent, but genetically distant, loops in exons 3 and 4.
31702909	8	19	theme	glycosylation	1300:1312	arg1	sites					1314:1318	all N-linked glycosylation sites	1287:1318	all N-linked glycosylation sites removed successfully	1287:1339	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	3	20	theme	development	798:808	arg1	types					771:775	various types	763:775	various types of CD19 research and development	763:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	7	21	theme	additional	1213:1222	arg1	variant					1229:1235	additional CD19 variant design and analysis	1213:1255	additional CD19 variant design and analysis	1213:1255	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	3	22	theme	FMC63-the	631:639	arg1	antibody					655:662	binding FMC63-the dominant CD19 antibody	623:662	binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development	623:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	1	23	theme	life	134:137	arg1	cycle					139:143	the cell life cycle	125:143	the cell life cycle	125:143	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	9	24	theme	protein	1548:1554	arg1	applications					1556:1567	fusion protein applications	1541:1567	fusion protein applications	1541:1567	Screening for thermally stable variants identified mutations to guide further CD19 stabilization for fusion protein applications and revealed evolutionary affinity-stability trade-offs.
31702909	7	25	theme	tolerance	1183:1191	arg1	data					1193:1196	the mutational tolerance data	1168:1196	the mutational tolerance data	1168:1196	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	5	26	theme	conformational	936:949	arg1	epitope					951:957	The FMC63 conformational epitope	926:957	The FMC63 conformational epitope	926:957	The FMC63 conformational epitope spans spatially adjacent, but genetically distant, loops in exons 3 and 4.
31702909	2	27	theme	tailored	376:383	arg1	development					385:395	more tailored development	371:395	more tailored development	371:395	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	9	28	theme	evolutionary	1582:1593	arg1	trade-offs					1614:1623	evolutionary affinity-stability trade-offs	1582:1623	evolutionary affinity-stability trade-offs	1582:1623	Screening for thermally stable variants identified mutations to guide further CD19 stabilization for fusion protein applications and revealed evolutionary affinity-stability trade-offs.
31702909	6	29	theme	peptide	1063:1069	arg1	epitope					1043:1049	The 3B10 epitope	1034:1049	The 3B10 epitope	1034:1049	The 3B10 epitope is a linear peptide sequence that binds CD19 with 440 pM affinity.
31702909	6	29	theme	peptide	1063:1069	arg1	sequence					1071:1078	a linear peptide sequence	1054:1078	a linear peptide sequence that binds CD19 with 440 pM affinity	1054:1115	The 3B10 epitope is a linear peptide sequence that binds CD19 with 440 pM affinity.
31702909	8	30	theme	yeast	1363:1367	arg1	context					1377:1383	the yeast display context	1359:1383	the yeast display context	1359:1383	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	7	31	theme	mapping	1159:1165	arg1	goal					1143:1146	their primary goal	1129:1146	their primary goal of epitope mapping	1129:1165	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	1	32	theme	cell	253:256	arg1	therapy					258:264	immune cell therapy	246:264	immune cell therapy	246:264	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	1	33	theme	surface	82:88	arg1	present					106:112	present	106:112	present	106:112	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	1	33	theme	surface	82:88	arg1	CD19					98:101	The B-cell surface protein CD19	71:101	The B-cell surface protein CD19	71:101	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	2	34	theme	therapeutics	414:425	arg1	study					361:365	fundamental study	349:365	fundamental study	349:365	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	2	34	theme	therapeutics	414:425	arg1	development					385:395	more tailored development	371:395	more tailored development	371:395	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	5	35	theme	adjacent	975:982	arg1	loops					1010:1014	spatially adjacent, but genetically distant, loops	965:1014	spatially adjacent, but genetically distant, loops	965:1014	The FMC63 conformational epitope spans spatially adjacent, but genetically distant, loops in exons 3 and 4.
31702909	3	36	theme	chimeric	672:679	arg1	receptor					689:696	chimeric antigen receptor	672:696	chimeric antigen receptor development-as	672:711	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	3	37	theme	antibody-binding	444:459	arg1	epitopes					461:468	the antibody-binding epitopes	440:468	the antibody-binding epitopes on CD19	440:476	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	7	38	theme	primary	1135:1141	arg1	goal					1143:1146	their primary goal	1129:1146	their primary goal of epitope mapping	1129:1165	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	4	39	theme	overlapping	846:856	arg1	epitopes					873:880	partially overlapping, yet distinct, epitopes	836:880	partially overlapping, yet distinct, epitopes	836:880	All three antibodies had partially overlapping, yet distinct, epitopes near the published epitope of antibody B43.
31702909	3	40	from	epitopes	461:468	arg1	CD19					473:476	CD19	473:476	CD19	473:476	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	2	41	theme	CD19	321:324	arg1	binding					310:316	the binding	306:316	the binding of CD19 to antibodies	306:338	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	0	42	theme	Extracellular	33:45	arg1	Domain					47:52	the CD19 Extracellular Domain	24:52	the CD19 Extracellular Domain	24:52	Fine Epitope Mapping of the CD19 Extracellular Domain Promotes Design.
31702909	2	43	theme	binding	310:316	arg1	dependence					292:301	the sequence dependence	279:301	the sequence dependence of the binding of CD19 to antibodies	279:338	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	8	44	from	antibody	1347:1354	arg1	context					1377:1383	the yeast display context	1359:1383	the yeast display context	1359:1383	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	6	45	theme	440	1101:1103	arg1	pM					1105:1106	pM	1105:1106	pM	1105:1106	The 3B10 epitope is a linear peptide sequence that binds CD19 with 440 pM affinity.
31702909	3	46	theme	receptor	689:696	arg1	development-as					698:711	chimeric antigen receptor development-as	672:711	chimeric antigen receptor development-as	672:711	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	3	47	theme	saturation	519:528	arg1	library					539:545	a comprehensive single-site saturation mutation library	491:545	a comprehensive single-site saturation mutation library of the human CD19 extracellular domain	491:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	3	48	theme	comprehensive	493:505	arg1	library					539:545	a comprehensive single-site saturation mutation library	491:545	a comprehensive single-site saturation mutation library of the human CD19 extracellular domain	491:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	1	49	theme	antigen	218:224	arg1	receptor					226:233	chimeric antigen receptor	209:233	chimeric antigen receptor engineered immune cell therapy	209:264	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	8	50	gly	aglycosylated	1412:1424	arg1	applications					1426:1437	aglycosylated applications	1412:1437	aglycosylated applications	1412:1437	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	10	51	theme	CD19	1658:1661	arg1	relationships					1681:1693	CD19 sequence-function relationships	1658:1693	CD19 sequence-function relationships	1658:1693	These fundamental insights into CD19 sequence-function relationships enhance our understanding of antibody-mediated CD19-targeted therapeutics.
31702909	3	52	theme	domain	579:584	arg1	library					539:545	a comprehensive single-site saturation mutation library	491:545	a comprehensive single-site saturation mutation library of the human CD19 extracellular domain	491:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	4	53	theme	distinct	863:870	arg1	epitopes					873:880	partially overlapping, yet distinct, epitopes	836:880	partially overlapping, yet distinct, epitopes	836:880	All three antibodies had partially overlapping, yet distinct, epitopes near the published epitope of antibody B43.
31702909	3	54	theme	CD19	560:563	arg1	domain					579:584	the human CD19 extracellular domain	550:584	the human CD19 extracellular domain	550:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	9	55	theme	stable	1464:1469	arg1	variants					1471:1478	thermally stable variants	1454:1478	thermally stable variants	1454:1478	Screening for thermally stable variants identified mutations to guide further CD19 stabilization for fusion protein applications and revealed evolutionary affinity-stability trade-offs.
31702909	2	56	theme	fundamental	349:359	arg1	study					361:365	fundamental study	349:365	fundamental study	349:365	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	3	57	theme	detrimental	608:618	arg1	mutations					598:606	mutations	598:606	mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development	598:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	8	58	theme	CD19	1269:1272	arg1	variant					1274:1280	A designed CD19 variant	1258:1280	A designed CD19 variant with all N-linked glycosylation sites removed successfully	1258:1339	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	3	59	theme	CD19	780:783	arg1	research					785:792	CD19 research	780:792	CD19 research	780:792	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	3	60	theme	dominant	641:648	arg1	antibody					655:662	binding FMC63-the dominant CD19 antibody	623:662	binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development	623:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	9	61	theme	further	1510:1516	arg1	stabilization					1523:1535	further CD19 stabilization	1510:1535	further CD19 stabilization for fusion protein applications	1510:1567	Screening for thermally stable variants identified mutations to guide further CD19 stabilization for fusion protein applications and revealed evolutionary affinity-stability trade-offs.
31702909	2	62	theme	sequence	283:290	arg1	dependence					292:301	the sequence dependence	279:301	the sequence dependence of the binding of CD19 to antibodies	279:338	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	4	63	theme	antibody	912:919	arg1	B43					921:923	antibody B43	912:923	antibody B43	912:923	All three antibodies had partially overlapping, yet distinct, epitopes near the published epitope of antibody B43.
31702909	3	64	theme	binding	623:629	arg1	antibody					655:662	binding FMC63-the dominant CD19 antibody	623:662	binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development	623:808	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	1	65	theme	cell	129:132	arg1	cycle					139:143	the cell life cycle	125:143	the cell life cycle	125:143	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	10	66	theme	fundamental	1632:1642	arg1	insights					1644:1651	These fundamental insights	1626:1651	These fundamental insights into CD19 sequence-function relationships	1626:1693	These fundamental insights into CD19 sequence-function relationships enhance our understanding of antibody-mediated CD19-targeted therapeutics.
31702909	8	67	theme	N-linked	1291:1298	arg1	sites					1314:1318	all N-linked glycosylation sites	1287:1318	all N-linked glycosylation sites removed successfully	1287:1339	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	9	68	theme	fusion	1541:1546	arg1	applications					1556:1567	fusion protein applications	1541:1567	fusion protein applications	1541:1567	Screening for thermally stable variants identified mutations to guide further CD19 stabilization for fusion protein applications and revealed evolutionary affinity-stability trade-offs.
31702909	7	69	theme	mutational	1172:1181	arg1	data					1193:1196	the mutational tolerance data	1168:1196	the mutational tolerance data	1168:1196	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	4	70	contain	had	832:834	arg2	epitopes					873:880	partially overlapping, yet distinct, epitopes	836:880	partially overlapping, yet distinct, epitopes	836:880	All three antibodies had partially overlapping, yet distinct, epitopes near the published epitope of antibody B43.
31702909	4	70	contain	had	832:834	arg1	antibodies					821:830	All three antibodies	811:830	All three antibodies	811:830	All three antibodies had partially overlapping, yet distinct, epitopes near the published epitope of antibody B43.
31702909	8	71	gly	glycosylation	1300:1312	arg2	sites					1314:1318	all N-linked glycosylation sites	1287:1318	all N-linked glycosylation sites removed successfully	1287:1339	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	10	72	theme	antibody-mediated	1724:1740	arg1	therapeutics					1756:1767	antibody-mediated CD19-targeted therapeutics	1724:1767	antibody-mediated CD19-targeted therapeutics	1724:1767	These fundamental insights into CD19 sequence-function relationships enhance our understanding of antibody-mediated CD19-targeted therapeutics.
31702909	0	73	theme	Epitope	5:11	arg1	Mapping					13:19	Fine Epitope Mapping	0:19	Fine Epitope Mapping of the CD19 Extracellular Domain	0:52	Fine Epitope Mapping of the CD19 Extracellular Domain Promotes Design.
31702909	1	74	theme	B-cell	75:80	arg1	present					106:112	present	106:112	present	106:112	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	1	74	theme	B-cell	75:80	arg1	CD19					98:101	The B-cell surface protein CD19	71:101	The B-cell surface protein CD19	71:101	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	6	75	theme	linear	1056:1061	arg1	epitope					1043:1049	The 3B10 epitope	1034:1049	The 3B10 epitope	1034:1049	The 3B10 epitope is a linear peptide sequence that binds CD19 with 440 pM affinity.
31702909	6	75	theme	linear	1056:1061	arg1	sequence					1071:1078	a linear peptide sequence	1054:1078	a linear peptide sequence that binds CD19 with 440 pM affinity	1054:1115	The 3B10 epitope is a linear peptide sequence that binds CD19 with 440 pM affinity.
31702909	1	76	theme	protein	90:96	arg1	present					106:112	present	106:112	present	106:112	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	1	76	theme	protein	90:96	arg1	CD19					98:101	The B-cell surface protein CD19	71:101	The B-cell surface protein CD19	71:101	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	8	77	theme	display	1369:1375	arg1	context					1377:1383	the yeast display context	1359:1383	the yeast display context	1359:1383	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	2	78	theme	CD19-targeted	400:412	arg1	therapeutics					414:425	CD19-targeted therapeutics	400:425	CD19-targeted therapeutics	400:425	Identifying the sequence dependence of the binding of CD19 to antibodies empowers fundamental study and more tailored development of CD19-targeted therapeutics.
31702909	0	79	theme	CD19	28:31	arg1	Domain					47:52	the CD19 Extracellular Domain	24:52	the CD19 Extracellular Domain	24:52	Fine Epitope Mapping of the CD19 Extracellular Domain Promotes Design.
31702909	10	80	theme	CD19-targeted	1742:1754	arg1	therapeutics					1756:1767	antibody-mediated CD19-targeted therapeutics	1724:1767	antibody-mediated CD19-targeted therapeutics	1724:1767	These fundamental insights into CD19 sequence-function relationships enhance our understanding of antibody-mediated CD19-targeted therapeutics.
31702909	8	81	with	variant	1274:1280	arg1	sites					1314:1318	all N-linked glycosylation sites	1287:1318	all N-linked glycosylation sites removed successfully	1287:1339	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	10	82	theme	therapeutics	1756:1767	arg1	understanding					1707:1719	our understanding	1703:1719	our understanding of antibody-mediated CD19-targeted therapeutics	1703:1767	These fundamental insights into CD19 sequence-function relationships enhance our understanding of antibody-mediated CD19-targeted therapeutics.
31702909	0	83	theme	Domain	47:52	arg1	Mapping					13:19	Fine Epitope Mapping	0:19	Fine Epitope Mapping of the CD19 Extracellular Domain	0:52	Fine Epitope Mapping of the CD19 Extracellular Domain Promotes Design.
31702909	6	84	theme	pM	1105:1106	arg1	affinity					1108:1115	440 pM affinity	1101:1115	440 pM affinity	1101:1115	The 3B10 epitope is a linear peptide sequence that binds CD19 with 440 pM affinity.
31702909	5	85	theme	distant	1001:1007	arg1	loops					1010:1014	spatially adjacent, but genetically distant, loops	965:1014	spatially adjacent, but genetically distant, loops	965:1014	The FMC63 conformational epitope spans spatially adjacent, but genetically distant, loops in exons 3 and 4.
31702909	3	86	theme	antigen	681:687	arg1	receptor					689:696	chimeric antigen receptor	672:696	chimeric antigen receptor development-as	672:711	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	1	87	dep	it	193:194	arg1	target					198:203	a target	196:203	it a target for chimeric antigen receptor engineered immune cell therapy	193:264	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
31702909	3	88	theme	mutation	530:537	arg1	library					539:545	a comprehensive single-site saturation mutation library	491:545	a comprehensive single-site saturation mutation library of the human CD19 extracellular domain	491:584	To identify the antibody-binding epitopes on CD19, we screened a comprehensive single-site saturation mutation library of the human CD19 extracellular domain to identify mutations detrimental to binding FMC63-the dominant CD19 antibody used in chimeric antigen receptor development-as well as 4G7-2E3 and 3B10, which have been used in various types of CD19 research and development.
31702909	8	89	theme	aglycosylated	1412:1424	arg1	applications					1426:1437	aglycosylated applications	1412:1437	aglycosylated applications	1412:1437	A designed CD19 variant with all N-linked glycosylation sites removed successfully bound antibody in the yeast display context, which provides a lead for aglycosylated applications.
31702909	7	90	theme	epitope	1151:1157	arg1	mapping					1159:1165	epitope mapping	1151:1165	epitope mapping	1151:1165	Along with their primary goal of epitope mapping, the mutational tolerance data also empowered additional CD19 variant design and analysis.
31702909	1	91	theme	chimeric	209:216	arg1	receptor					226:233	chimeric antigen receptor	209:233	chimeric antigen receptor engineered immune cell therapy	209:264	The B-cell surface protein CD19 is present throughout the cell life cycle and is uniformly expressed in leukemias, making it a target for chimeric antigen receptor engineered immune cell therapy.
30898768	3	0	theme	IV	316:317	arg1	pili					319:322	archaeal and bacterial type IV pili	288:322	archaeal and bacterial type IV pili	288:322	Archaella are related to archaeal and bacterial type IV pili.
30898768	5	1	theme	maripaludis	791:801	arg1	archaella					803:811	Methanococcus maripaludis archaella	777:811	Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis	777:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	8	2	theme	metal-binding	1073:1085	arg1	site					1087:1090	a highly conserved metal-binding site	1054:1090	a highly conserved metal-binding site	1054:1090	The crystal structure reveals a highly conserved metal-binding site, which is validated by mass spectrometry and electron energy-loss spectroscopy.
30898768	4	3	theme	archaellum	401:410	arg1	assembly					412:419	archaellum assembly	401:419	archaellum assembly	401:419	Despite recent advances, our understanding of molecular processes governing archaellum assembly and stability is still incomplete.
30898768	5	4	theme	biological	725:734	arg1	context					736:742	biological context	725:742	biological context	725:742	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	5	from	archaella	803:811	arg1	reconstruction					757:770	a cryo-EM reconstruction	747:770	a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis	747:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	6	theme	only	632:635	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	6	theme	only	632:635	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	1	7	theme	Many	77:80	arg1	archaea					82:88	Many archaea	77:88	Many archaea	77:88	Many archaea swim by means of archaella.
30898768	5	8	theme	crystal	637:643	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	8	theme	crystal	637:643	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	9	theme	archaella	507:515	arg1	structures					479:488	the structures	475:488	the structures of Methanococcus archaella	475:515	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	10	theme	4 Å	816:818	arg1	resolution					820:829	4 Å resolution	816:829	4 Å resolution created with helical single-particle analysis	816:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	11	from	resolution	820:829	arg1	archaella					803:811	Methanococcus maripaludis archaella	777:811	Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis	777:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	0	12	theme	conserved	47:55	arg1	site					71:74	a conserved metal-binding site	45:74	a conserved metal-binding site	45:74	High-resolution archaellum structure reveals a conserved metal-binding site.
30898768	5	13	theme	jannaschii	598:607	arg1	FlaB1					609:613	Methanocaldococcus jannaschii FlaB1	579:613	Methanocaldococcus jannaschii FlaB1	579:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	0	14	theme	archaellum	16:25	arg1	structure					27:35	High-resolution archaellum structure	0:35	High-resolution archaellum structure	0:35	High-resolution archaellum structure reveals a conserved metal-binding site.
30898768	8	15	theme	mass	1115:1118	arg1	spectrometry					1120:1131	mass spectrometry	1115:1131	mass spectrometry	1115:1131	The crystal structure reveals a highly conserved metal-binding site, which is validated by mass spectrometry and electron energy-loss spectroscopy.
30898768	5	16	theme	FlaB1	609:613	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	16	theme	FlaB1	609:613	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	17	theme	X-ray	520:524	arg1	crystallography					526:540	X-ray crystallography	520:540	X-ray crystallography	520:540	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	0	18	theme	High-resolution	0:14	arg1	structure					27:35	High-resolution archaellum structure	0:35	High-resolution archaellum structure	0:35	High-resolution archaellum structure reveals a conserved metal-binding site.
30898768	5	19	theme	archaellin	662:671	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	19	theme	archaellin	662:671	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	4	20	theme	processes	381:389	arg1	understanding					354:366	our understanding	350:366	our understanding of molecular processes governing archaellum assembly and stability	350:433	Despite recent advances, our understanding of molecular processes governing archaellum assembly and stability is still incomplete.
30898768	8	21	theme	conserved	1063:1071	arg1	site					1087:1090	a highly conserved metal-binding site	1054:1090	a highly conserved metal-binding site	1054:1090	The crystal structure reveals a highly conserved metal-binding site, which is validated by mass spectrometry and electron energy-loss spectroscopy.
30898768	4	22	theme	molecular	371:379	arg1	processes					381:389	molecular processes	371:389	molecular processes governing archaellum assembly and stability	371:433	Despite recent advances, our understanding of molecular processes governing archaellum assembly and stability is still incomplete.
30898768	5	23	theme	first	622:626	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	23	theme	first	622:626	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	24	theme	single-particle	852:866	arg1	analysis					868:875	helical single-particle analysis	844:875	helical single-particle analysis	844:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	25	theme	helical	844:850	arg1	analysis					868:875	helical single-particle analysis	844:875	helical single-particle analysis	844:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	2	26	from	similar	142:148	arg1	function					153:160	function	153:160	function	153:160	While the archaellum is similar in function to its bacterial counterpart, its structure, composition, and evolution are fundamentally different.
30898768	8	27	theme	energy-loss	1146:1156	arg1	spectroscopy					1158:1169	electron energy-loss spectroscopy	1137:1169	electron energy-loss spectroscopy	1137:1169	The crystal structure reveals a highly conserved metal-binding site, which is validated by mass spectrometry and electron energy-loss spectroscopy.
30898768	2	28	theme	bacterial	169:177	arg1	counterpart					179:189	its bacterial counterpart	165:189	its bacterial counterpart	165:189	While the archaellum is similar in function to its bacterial counterpart, its structure, composition, and evolution are fundamentally different.
30898768	8	29	theme	electron	1137:1144	arg1	spectroscopy					1158:1169	electron energy-loss spectroscopy	1137:1169	electron energy-loss spectroscopy	1137:1169	The crystal structure reveals a highly conserved metal-binding site, which is validated by mass spectrometry and electron energy-loss spectroscopy.
30898768	5	30	from	resolution	686:695	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	30	from	resolution	686:695	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	31	theme	crystal	558:564	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	31	theme	crystal	558:564	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	2	32	from	function	153:160	arg1	similar					142:148	similar	142:148	similar	142:148	While the archaellum is similar in function to its bacterial counterpart, its structure, composition, and evolution are fundamentally different.
30898768	2	32	from	function	153:160	arg1	archaellum					128:137	the archaellum	124:137	the archaellum	124:137	While the archaellum is similar in function to its bacterial counterpart, its structure, composition, and evolution are fundamentally different.
30898768	3	33	theme	bacterial	301:309	arg1	pili					319:322	archaeal and bacterial type IV pili	288:322	archaeal and bacterial type IV pili	288:322	Archaella are related to archaeal and bacterial type IV pili.
30898768	9	34	theme	filament	1291:1298	arg1	integrity					1300:1308	filament integrity	1291:1308	filament integrity	1291:1308	We show in vitro that the metal-binding site, which appears to be a widespread property of archaellin, is required for filament integrity.
30898768	4	35	theme	recent	333:338	arg1	advances					340:347	recent advances	333:347	recent advances	333:347	Despite recent advances, our understanding of molecular processes governing archaellum assembly and stability is still incomplete.
30898768	0	36	theme	metal-binding	57:69	arg1	site					71:74	a conserved metal-binding site	45:74	a conserved metal-binding site	45:74	High-resolution archaellum structure reveals a conserved metal-binding site.
30898768	9	37	theme	archaellin	1263:1272	arg1	site					1212:1215	the metal-binding site	1194:1215	the metal-binding site	1194:1215	We show in vitro that the metal-binding site, which appears to be a widespread property of archaellin, is required for filament integrity.
30898768	9	37	theme	archaellin	1263:1272	arg1	property					1251:1258	a widespread property	1238:1258	a widespread property of archaellin	1238:1272	We show in vitro that the metal-binding site, which appears to be a widespread property of archaellin, is required for filament integrity.
30898768	3	38	theme	type	311:314	arg1	pili					319:322	archaeal and bacterial type IV pili	288:322	archaeal and bacterial type IV pili	288:322	Archaella are related to archaeal and bacterial type IV pili.
30898768	7	39	theme	N-linked	967:974	arg1	glycosylation					976:988	N-linked glycosylation	967:988	N-linked glycosylation	967:988	We identify N-linked glycosylation by cryo-EM and mass spectrometry.
30898768	3	40	theme	archaeal	288:295	arg1	pili					319:322	archaeal and bacterial type IV pili	288:322	archaeal and bacterial type IV pili	288:322	Archaella are related to archaeal and bacterial type IV pili.
30898768	9	41	theme	metal-binding	1198:1210	arg1	property					1251:1258	a widespread property	1238:1258	a widespread property of archaellin	1238:1272	We show in vitro that the metal-binding site, which appears to be a widespread property of archaellin, is required for filament integrity.
30898768	9	41	theme	metal-binding	1198:1210	arg1	site					1212:1215	the metal-binding site	1194:1215	the metal-binding site	1194:1215	We show in vitro that the metal-binding site, which appears to be a widespread property of archaellin, is required for filament integrity.
30898768	8	42	theme	crystal	1028:1034	arg1	structure					1036:1044	The crystal structure	1024:1044	The crystal structure	1024:1044	The crystal structure reveals a highly conserved metal-binding site, which is validated by mass spectrometry and electron energy-loss spectroscopy.
30898768	9	43	theme	widespread	1240:1249	arg1	site					1212:1215	the metal-binding site	1194:1215	the metal-binding site	1194:1215	We show in vitro that the metal-binding site, which appears to be a widespread property of archaellin, is required for filament integrity.
30898768	9	43	theme	widespread	1240:1249	arg1	property					1251:1258	a widespread property	1238:1258	a widespread property of archaellin	1238:1272	We show in vitro that the metal-binding site, which appears to be a widespread property of archaellin, is required for filament integrity.
30898768	7	44	link	N-linked	967:974	arg1	glycosylation					976:988	N-linked glycosylation	967:988	N-linked glycosylation	967:988	We identify N-linked glycosylation by cryo-EM and mass spectrometry.
30898768	5	45	theme	cryo-EM	749:755	arg1	reconstruction					757:770	a cryo-EM reconstruction	747:770	a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis	747:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	7	46	theme	mass	1005:1008	arg1	spectrometry					1010:1021	mass spectrometry	1005:1021	mass spectrometry	1005:1021	We identify N-linked glycosylation by cryo-EM and mass spectrometry.
30898768	5	47	theme	1.5 Å	700:704	arg1	resolution					686:695	a resolution	684:695	a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis	684:875	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	48	dep	determine	465:473	arg1	structure					566:574	The crystal structure	554:574	The crystal structure of Methanocaldococcus jannaschii FlaB1	554:613	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30898768	5	48	dep	determine	465:473	arg1	structure					645:653	the first and only crystal structure	618:653	the first and only crystal structure of any archaellin to date	618:679	Here, we determine the structures of Methanococcus archaella by X-ray crystallography and cryo-EM The crystal structure of Methanocaldococcus jannaschii FlaB1 is the first and only crystal structure of any archaellin to date at a resolution of 1.5 Å, which is put into biological context by a cryo-EM reconstruction from Methanococcus maripaludis archaella at 4 Å resolution created with helical single-particle analysis.
30243592	0	0	theme	inhibitors	79:88	arg1	Optimization					0:11	Optimization	0:11	Optimization of the efflux ratio	0:31	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	0	0	theme	inhibitors	79:88	arg1	permeability					37:48	permeability	37:48	permeability of covalent irreversible BTK inhibitors	37:88	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	3	1	theme	kinase	629:634	arg1	domain					636:641	the Btk kinase domain	621:641	the Btk kinase domain	621:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	2	2	theme	irreversible	291:302	arg1	inhibitors					308:317	Small molecule covalent irreversible Btk inhibitors	267:317	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket	267:364	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	3	3	contain	bear	532:535	arg2	groups					546:551	N-linked groups	537:551	N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	537:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	3	contain	bear	532:535	arg1	inhibitors					516:525	potent covalent irreversible Btk inhibitors	483:525	potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	483:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	0	4	theme	BTK	75:77	arg1	inhibitors					79:88	covalent irreversible BTK inhibitors	53:88	covalent irreversible BTK inhibitors	53:88	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	5	5	theme	steric	793:798	arg1	hindrance					800:808	installing steric hindrance	782:808	installing steric hindrance	782:808	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	5	5	theme	steric	793:798	arg1	tPSA					776:779	tPSA	776:779	tPSA	776:779	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	2	6	theme	covalent	282:289	arg1	inhibitors					308:317	Small molecule covalent irreversible Btk inhibitors	267:317	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket	267:364	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	4	7	theme	efflux	701:706	arg1	ER					715:716	ER	715:716	ER	715:716	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	4	7	theme	efflux	701:706	arg1	ratio					708:712	high P-gp mediated efflux ratio	682:712	high P-gp mediated efflux ratio (ER)	682:717	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	5	8	theme	efflux	897:902	arg1	ratio					904:908	efflux ratio	897:908	efflux ratio	897:908	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	4	9	theme	high	682:685	arg1	ER					715:716	ER	715:716	ER	715:716	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	4	9	theme	high	682:685	arg1	ratio					708:712	high P-gp mediated efflux ratio	682:712	high P-gp mediated efflux ratio (ER)	682:717	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	3	10	theme	irreversible	499:510	arg1	inhibitors					516:525	potent covalent irreversible Btk inhibitors	483:525	potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	483:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	1	11	theme	B	217:217	arg1	cells					219:223	B cells	217:223	B cells	217:223	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	3	12	theme	potent	483:488	arg1	inhibitors					516:525	potent covalent irreversible Btk inhibitors	483:525	potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	483:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	5	13	theme	hit	965:967	arg1	molecule					969:976	hit molecule 1	965:978	hit molecule 1	965:978	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	3	14	theme	novel	467:471	arg1	series					473:478	a novel series	465:478	a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	465:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	15	link	N-linked	537:544	arg1	groups					546:551	N-linked groups	537:551	N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	537:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	4	16	theme	P-gp	687:690	arg1	ER					715:716	ER	715:716	ER	715:716	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	4	16	theme	P-gp	687:690	arg1	ratio					708:712	high P-gp mediated efflux ratio	682:712	high P-gp mediated efflux ratio (ER)	682:717	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	1	17	theme	Tec	141:143	arg1	family					152:157	the Tec kinase family	137:157	the Tec kinase family	137:157	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	3	18	theme	Btk	512:514	arg1	inhibitors					516:525	potent covalent irreversible Btk inhibitors	483:525	potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	483:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	1	19	theme	kinase	145:150	arg1	family					152:157	the Tec kinase family	137:157	the Tec kinase family	137:157	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	4	20	theme	Caco-2	748:753	arg1	assay					755:759	Caco-2 assay	748:759	Caco-2 assay	748:759	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	3	21	theme	inhibitors	516:525	arg1	series					473:478	a novel series	465:478	a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	465:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	1	22	theme	family	152:157	arg1	kinase					109:114	Bruton's tyrosine kinase	91:114	Bruton's tyrosine kinase (Btk)	91:120	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	1	22	theme	family	152:157	arg1	member					127:132	a member	125:132	a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells)	125:264	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	0	23	theme	efflux	20:25	arg1	ratio					27:31	the efflux ratio	16:31	the efflux ratio	16:31	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	4	24	theme	poor	723:726	arg1	permeability					732:743	poor A-B permeability	723:743	poor A-B permeability	723:743	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	3	25	theme	covalent	490:497	arg1	inhibitors					516:525	potent covalent irreversible Btk inhibitors	483:525	potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	483:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	5	26	theme	top	835:837	arg1	molecule					839:846	one top molecule 9	831:848	one top molecule 9	831:848	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	4	27	theme	mediated	692:699	arg1	ER					715:716	ER	715:716	ER	715:716	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	4	27	theme	mediated	692:699	arg1	ratio					708:712	high P-gp mediated efflux ratio	682:712	high P-gp mediated efflux ratio (ER)	682:717	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	1	28	theme	tyrosine	100:107	arg1	Btk					117:119	Btk	117:119	Btk	117:119	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	1	28	theme	tyrosine	100:107	arg1	kinase					109:114	Bruton's tyrosine kinase	91:114	Bruton's tyrosine kinase (Btk)	91:120	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	1	28	theme	tyrosine	100:107	arg1	member					127:132	a member	125:132	a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells)	125:264	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	5	29	from	decrease	885:892	arg1	permeability					940:951	A-B permeability	936:951	A-B permeability	936:951	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	5	29	from	decrease	885:892	arg1	ratio					904:908	efflux ratio	897:908	efflux ratio	897:908	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	5	30	theme	A-B	936:938	arg1	permeability					940:951	A-B permeability	936:951	A-B permeability	936:951	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	3	31	theme	N-linked	537:544	arg1	groups					546:551	N-linked groups	537:551	N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	537:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	5	32	dep	showed	872:877	arg1	compared					953:960	compared	953:960	showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1	872:978	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	0	33	theme	ratio	27:31	arg1	Optimization					0:11	Optimization	0:11	Optimization of the efflux ratio	0:31	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	0	33	theme	ratio	27:31	arg1	permeability					37:48	permeability	37:48	permeability of covalent irreversible BTK inhibitors	37:88	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	2	34	theme	malignancies	411:422	arg1	treatment					391:399	the treatment	387:399	the treatment of B-cell malignancies	387:422	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	1	35	dep	cells	180:184	arg1	monocytes					239:247	monocytes	239:247	monocytes	239:247	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	1	35	dep	cells	180:184	arg1	cells					219:223	B cells	217:223	B cells	217:223	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	1	35	dep	cells	180:184	arg1	macrophages					226:236	macrophages	226:236	macrophages	226:236	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	1	35	dep	cells	180:184	arg1	cells					259:263	mast cells	254:263	mast cells	254:263	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	2	36	theme	ATP-binding	347:357	arg1	pocket					359:364	the ATP-binding pocket	343:364	the ATP-binding pocket	343:364	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	2	37	theme	B-cell	404:409	arg1	malignancies					411:422	B-cell malignancies	404:422	B-cell malignancies	404:422	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	5	38	from	increase	924:931	arg1	permeability					940:951	A-B permeability	936:951	A-B permeability	936:951	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	5	38	from	increase	924:931	arg1	ratio					904:908	efflux ratio	897:908	efflux ratio	897:908	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	4	39	theme	A-B	728:730	arg1	permeability					732:743	poor A-B permeability	723:743	poor A-B permeability	723:743	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	3	40	theme	domain	636:641	arg1	domain					636:641	the Btk kinase domain	621:641	the Btk kinase domain	621:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	40	theme	domain	636:641	arg1	site					613:616	the active site	602:616	the active site of the Btk kinase domain	602:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	2	41	theme	molecule	273:280	arg1	inhibitors					308:317	Small molecule covalent irreversible Btk inhibitors	267:317	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket	267:364	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	1	42	theme	mast	254:257	arg1	cells					259:263	mast cells	254:263	mast cells	254:263	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	3	43	theme	active	606:611	arg1	domain					636:641	the Btk kinase domain	621:641	the Btk kinase domain	621:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	43	theme	active	606:611	arg1	site					613:616	the active site	602:616	the active site of the Btk kinase domain	602:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	44	theme	site	613:616	arg1	SAP					594:596	SAP	594:596	SAP	594:596	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	44	theme	site	613:616	arg1	pocket					586:591	the solvent accessible pocket	563:591	the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	563:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	2	45	theme	Small	267:271	arg1	inhibitors					308:317	Small molecule covalent irreversible Btk inhibitors	267:317	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket	267:364	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	1	46	dep	cells	219:223	arg1	e.g.					212:215	e.g.	212:215	e.g.	212:215	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	3	47	theme	solvent	567:573	arg1	SAP					594:596	SAP	594:596	SAP	594:596	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	47	theme	solvent	567:573	arg1	pocket					586:591	the solvent accessible pocket	563:591	the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	563:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	4	48	theme	hit	648:650	arg1	molecules					652:660	The hit molecules	644:660	The hit molecules	644:660	The hit molecules, however, displayed high P-gp mediated efflux ratio (ER) and poor A-B permeability in Caco-2 assay.
30243592	5	49	theme	90-fold	916:922	arg1	increase					924:931	a 90-fold increase	914:931	a 90-fold increase in A-B permeability	914:951	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	3	50	theme	accessible	575:584	arg1	SAP					594:596	SAP	594:596	SAP	594:596	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	3	50	theme	accessible	575:584	arg1	pocket					586:591	the solvent accessible pocket	563:591	the solvent accessible pocket (SAP) of the active site of the Btk kinase domain	563:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	5	51	theme	installing	782:791	arg1	hindrance					800:808	installing steric hindrance	782:808	installing steric hindrance	782:808	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	5	51	theme	installing	782:791	arg1	tPSA					776:779	tPSA	776:779	tPSA	776:779	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	0	52	theme	irreversible	62:73	arg1	inhibitors					79:88	covalent irreversible BTK inhibitors	53:88	covalent irreversible BTK inhibitors	53:88	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	5	53	theme	99	881:882	arg1	%					883:883	%	883:883	%	883:883	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	1	54	theme	hematopoietic	189:201	arg1	lineage					203:209	hematopoietic lineage	189:209	hematopoietic lineage	189:209	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30243592	0	55	theme	covalent	53:60	arg1	inhibitors					79:88	covalent irreversible BTK inhibitors	53:88	covalent irreversible BTK inhibitors	53:88	Optimization of the efflux ratio and permeability of covalent irreversible BTK inhibitors.
30243592	3	56	theme	Btk	625:627	arg1	domain					636:641	the Btk kinase domain	621:641	the Btk kinase domain	621:641	Starting from a fragment, we discovered a novel series of potent covalent irreversible Btk inhibitors that bear N-linked groups occupying the solvent accessible pocket (SAP) of the active site of the Btk kinase domain.
30243592	5	57	theme	%	883:883	arg1	decrease					885:892	a 99% decrease	879:892	a 99% decrease in efflux ratio	879:908	By decreasing tPSA, installing steric hindrance and adjusting clogP, one top molecule 9 was discovered, which showed a 99% decrease in efflux ratio and a 90-fold increase in A-B permeability compared to hit molecule 1.
30243592	2	58	theme	Btk	304:306	arg1	inhibitors					308:317	Small molecule covalent irreversible Btk inhibitors	267:317	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket	267:364	Small molecule covalent irreversible Btk inhibitors targeting Cys481 within the ATP-binding pocket have been applied in the treatment of B-cell malignancies.
30243592	1	59	theme	lineage	203:209	arg1	cells					180:184	cells	180:184	cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells)	180:264	Bruton's tyrosine kinase (Btk) is a member of the Tec kinase family that is expressed in cells of hematopoietic lineage (e.g. B cells, macrophages, monocytes, and mast cells).
30147262	11	0	theme	structural	1803:1812	arg1	function					1814:1821	its antigenic and structural function	1785:1821	its antigenic and structural function	1785:1821	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	1	1	theme	disease	209:215	arg1	NDV					224:226	NDV	224:226	NDV	224:226	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	1	1	theme	disease	209:215	arg1	virus					217:221	Newcastle disease virus	199:221	Newcastle disease virus (NDV)	199:227	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	9	2	theme	Egyptian	1388:1395	arg1	strains					1397:1403	all Egyptian strains	1384:1403	all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4	1384:1490	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	12	3	from	evolution	1930:1938	arg1	Egypt					1955:1959	Egypt	1955:1959	Egypt	1955:1959	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	9	4	from	N	1476:1476	arg1	substitution					1454:1465	a substitution	1452:1465	a substitution at D 170 N	1452:1476	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	7	5	theme	F	1071:1071	arg1	gene					1073:1076	the F gene	1067:1076	the F gene	1067:1076	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	0	6	theme	Molecular	0:8	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId	0:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	12	7	theme	genotype	1897:1904	arg1	VIId					1906:1909	NDV genotype VIId	1893:1909	NDV genotype VIId	1893:1909	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	9	8	theme	study	1413:1417	arg1	strains					1397:1403	all Egyptian strains	1384:1403	all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4	1384:1490	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	6	9	theme	NDV	938:940	arg1	isolates					942:949	the seven NDV isolates	928:949	the seven NDV isolates	928:949	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	10	10	theme	cysteine	1516:1523	arg1	residues					1525:1532	10 cysteine residues	1513:1532	10 cysteine residues	1513:1532	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	7	11	theme	Phylogenetic	1042:1053	arg1	analysis					1055:1062	Phylogenetic analysis	1042:1062	Phylogenetic analysis of the F gene	1042:1076	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	12	12	theme	F	1883:1883	arg1	gene					1885:1888	sequence F gene	1874:1888	sequence F gene of NDV genotype VIId	1874:1909	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	1	13	from	evolution	286:294	arg1	Egypt					311:315	Egypt	311:315	Egypt	311:315	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	1	14	theme	full	175:178	arg1	sequence					187:194	the full F gene sequence	171:194	the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping	171:267	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	8	15	contain	have	1254:1257	arg2	sites					1296:1300	six potential N-linked glycosylation sites	1259:1300	six potential N-linked glycosylation sites	1259:1300	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	8	15	contain	have	1254:1257	arg1	Six					1222:1224	Six	1222:1224	Six	1222:1224	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	8	15	contain	have	1254:1257	arg1	isolates					1245:1252	seven sequenced isolates	1229:1252	seven sequenced isolates	1229:1252	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	8	16	theme	isolates	1245:1252	arg1	Six					1222:1224	Six	1222:1224	Six	1222:1224	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	8	16	theme	isolates	1245:1252	arg1	isolates					1245:1252	seven sequenced isolates	1229:1252	seven sequenced isolates	1229:1252	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	11	17	theme	Lasota	1743:1748	arg1	strain					1750:1755	Lasota strain	1743:1755	Lasota strain that reveals importance for its antigenic and structural function	1743:1821	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	5	18	theme	full-length	885:895	arg1	gene					899:902	full-length F gene	885:902	full-length F gene	885:902	Pathotyping and genotyping of these isolates were done through sequencing of full-length F gene.
30147262	9	19	theme	D	1470:1470	arg1	N					1476:1476	D 170 N	1470:1476	D 170 N	1470:1476	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	2	20	theme	vaccinated	421:430	arg1	chickens					432:439	vaccinated chickens	421:439	vaccinated chickens	421:439	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	8	21	theme	N-linked	1273:1280	arg1	sites					1296:1300	six potential N-linked glycosylation sites	1259:1300	six potential N-linked glycosylation sites	1259:1300	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	4	22	theme	isolates	657:664	arg1	Pathogenicity					632:644	Pathogenicity	632:644	Pathogenicity of the NDV isolates	632:664	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	0	23	theme	Newcastle	57:65	arg1	virus					75:79	Newcastle disease virus	57:79	Newcastle disease virus genotype VIId	57:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	9	24	theme	epitope	1481:1487	arg1	A4					1489:1490	epitope A4	1481:1490	epitope A4	1481:1490	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	3	25	attach	isolated	515:522	arg2	NDV					494:496	The NDV	490:496	The NDV	490:496	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	3	25	attach	isolated	515:522	arg1	specimens					542:550	pathological specimens	529:550	pathological specimens	529:550	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	6	26	theme	cleavage	973:980	arg1	112RRQKRF117					994:1005	112RRQKRF117	994:1005	112RRQKRF117	994:1005	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	6	26	theme	cleavage	973:980	arg1	motif					987:991	characteristic cleavage site motif	958:991	characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV	958:1039	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	11	27	theme	acid	1688:1691	arg1	substitutions					1693:1705	52 amino acid substitutions	1679:1705	52 amino acid substitutions within fusion gene	1679:1724	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	0	28	theme	virus	75:79	arg1	VIId					90:93	Newcastle disease virus genotype VIId	57:93	Newcastle disease virus genotype VIId	57:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	5	29	theme	gene	899:902	arg1	sequencing					871:880	sequencing	871:880	sequencing of full-length F gene	871:902	Pathotyping and genotyping of these isolates were done through sequencing of full-length F gene.
30147262	9	30	contain	has	1448:1450	arg1	NDV-KFR-B7-2012					1426:1440	NDV-KFR-B7-2012	1426:1440	NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4	1426:1490	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	9	30	contain	has	1448:1450	arg2	substitution					1454:1465	a substitution	1452:1465	a substitution at D 170 N	1452:1476	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	10	31	theme	residue	1579:1585	arg1	loss					1559:1562	one loss	1555:1562	one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016	1555:1634	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	0	32	theme	VIId	90:93	arg1	protein					42:48	full fusion protein	30:48	full fusion protein (F) of Newcastle disease virus genotype VIId	30:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	0	32	theme	VIId	90:93	arg1	F					51:51	F	51:51	F	51:51	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	8	33	gly	glycosylation	1282:1294	arg2	sites					1296:1300	six potential N-linked glycosylation sites	1259:1300	six potential N-linked glycosylation sites	1259:1300	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	8	33	gly	glycosylation	1282:1294	arg2	six					1259:1261	six	1259:1261	six	1259:1261	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	9	34	from	epitope	1322:1328	arg1	fusion					1361:1366	fusion	1361:1366	fusion	1361:1366	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	9	34	from	epitope	1322:1328	arg1	sites					1352:1356	the five antigenic sites	1333:1356	the five antigenic sites of fusion	1333:1366	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	4	35	theme	pathogenicity	707:719	arg1	index					721:725	intracerebral pathogenicity index	693:725	intracerebral pathogenicity index	693:725	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	10	36	theme	cysteine	1567:1574	arg1	residue					1579:1585	cysteine at residue 370	1567:1589	cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016	1567:1634	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	7	37	theme	Israeli	1142:1148	arg1	strains					1150:1156	Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains	1142:1219	Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains	1142:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	37	theme	Israeli	1142:1148	arg1	NDV-Ch/SD883					1171:1182	NDV-Ch/SD883	1171:1182	NDV-Ch/SD883	1171:1182	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	37	theme	Israeli	1142:1148	arg1	NDV/IS/2015					1158:1168	NDV/IS/2015	1158:1168	NDV/IS/2015	1158:1168	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	11	38	theme	CONCLUSION	1637:1646	arg1	viruses					1652:1658	CONCLUSION All viruses	1637:1658	CONCLUSION All viruses in this study	1637:1672	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	2	39	theme	present	344:350	arg1	study					352:356	The present study	340:356	MATERIALS AND METHODS The present study	318:356	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	7	40	theme	VIId	1130:1133	arg1	VIId					1130:1133	genotype VIId	1121:1133	genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains	1121:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	40	theme	VIId	1130:1133	arg1	Group					1110:1114	Group I	1110:1116	Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains	1110:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	9	41	theme	neutralization	1307:1320	arg1	epitope					1322:1328	The neutralization epitope	1303:1328	The neutralization epitope on the five antigenic sites of fusion	1303:1366	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	6	42	theme	velogenic	1016:1024	arg1	strains					1026:1032	the velogenic strains	1012:1032	the velogenic strains of NDV	1012:1039	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	2	43	theme	suspected	397:405	arg1	flocks					411:416	seven suspected NDV flocks	391:416	seven suspected NDV flocks of vaccinated chickens	391:439	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	3	44	theme	chicken	610:616	arg1	eggs					618:621	specific pathogen-free embryonated chicken eggs	575:621	specific pathogen-free embryonated chicken eggs	575:621	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	0	45	theme	fusion	35:40	arg1	protein					42:48	full fusion protein	30:48	full fusion protein (F) of Newcastle disease virus genotype VIId	30:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	0	45	theme	fusion	35:40	arg1	F					51:51	F	51:51	F	51:51	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	7	46	dep	strains	1150:1156	arg1	strains					1213:1219	the Middle East strains	1197:1219	the Middle East strains	1197:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	46	dep	strains	1150:1156	arg1	strains					1150:1156	Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains	1142:1219	Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains	1142:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	46	dep	strains	1150:1156	arg1	NDV-Ch/SD883					1171:1182	NDV-Ch/SD883	1171:1182	NDV-Ch/SD883	1171:1182	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	46	dep	strains	1150:1156	arg1	most					1189:1192	most	1189:1192	most	1189:1192	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	46	dep	strains	1150:1156	arg1	NDV/IS/2015					1158:1168	NDV/IS/2015	1158:1168	NDV/IS/2015	1158:1168	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	3	47	theme	pathogen-free	584:596	arg1	eggs					618:621	specific pathogen-free embryonated chicken eggs	575:621	specific pathogen-free embryonated chicken eggs	575:621	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	4	48	theme	NDV	794:796	arg1	isolates					798:805	NDV isolates	794:805	NDV isolates	794:805	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	10	49	from	loss	1559:1562	arg1	NDV-GHB-328F-2016					1618:1634	NDV-GHB-328F-2016	1618:1634	NDV-GHB-328F-2016	1618:1634	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	10	49	from	loss	1559:1562	arg1	NDV-EG-35-2014					1599:1612	NDV-EG-35-2014	1599:1612	NDV-EG-35-2014	1599:1612	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	10	50	from	residue	1579:1585	arg1	NDV-GHB-328F-2016					1618:1634	NDV-GHB-328F-2016	1618:1634	NDV-GHB-328F-2016	1618:1634	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	10	50	from	residue	1579:1585	arg1	NDV-EG-35-2014					1599:1612	NDV-EG-35-2014	1599:1612	NDV-EG-35-2014	1599:1612	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	1	51	theme	F	180:180	arg1	sequence					187:194	the full F gene sequence	171:194	the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping	171:267	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	4	52	dep	RESULTS	624:630	arg1	estimated					675:683	estimated	675:683	estimated through intracerebral pathogenicity index	675:725	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	4	52	dep	RESULTS	624:630	arg1	ranged					731:736	ranged	731:736	ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates	731:805	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	2	53	dep	MATERIALS	318:326	arg1	study					352:356	The present study	340:356	MATERIALS AND METHODS The present study	318:356	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	9	54	theme	fusion	1361:1366	arg1	fusion					1361:1366	fusion	1361:1366	fusion	1361:1366	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	9	54	theme	fusion	1361:1366	arg1	sites					1352:1356	the five antigenic sites	1333:1356	the five antigenic sites of fusion	1333:1366	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	10	55	from	NDV-EG-35-2014	1599:1612	arg1	loss					1559:1562	one loss	1555:1562	one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016	1555:1634	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	1	56	theme	Newcastle	199:207	arg1	NDV					224:226	NDV	224:226	NDV	224:226	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	1	56	theme	Newcastle	199:207	arg1	virus					217:221	Newcastle disease virus	199:221	Newcastle disease virus (NDV)	199:227	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	10	57	from	NDV-GHB-328F-2016	1618:1634	arg1	loss					1559:1562	one loss	1555:1562	one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016	1555:1634	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	7	58	theme	Middle	1201:1206	arg1	strains					1213:1219	the Middle East strains	1197:1219	the Middle East strains	1197:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	7	59	theme	gene	1073:1076	arg1	analysis					1055:1062	Phylogenetic analysis	1042:1062	Phylogenetic analysis of the F gene	1042:1076	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	1	60	theme	virus	217:221	arg1	sequence					187:194	the full F gene sequence	171:194	the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping	171:267	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	8	61	link	N-linked	1273:1280	arg1	sites					1296:1300	six potential N-linked glycosylation sites	1259:1300	six potential N-linked glycosylation sites	1259:1300	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	4	62	theme	isolates	798:805	arg1	type					786:789	the velogenic type	772:789	the velogenic type of NDV isolates	772:805	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	11	63	contain	have	1674:1677	arg1	viruses					1652:1658	CONCLUSION All viruses	1637:1658	CONCLUSION All viruses in this study	1637:1672	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	11	63	contain	have	1674:1677	arg2	substitutions					1693:1705	52 amino acid substitutions	1679:1705	52 amino acid substitutions within fusion gene	1679:1724	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	1	64	theme	work	153:156	arg1	aim					141:143	The aim	137:143	The aim of this work	137:156	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	12	65	theme	NDV	1893:1895	arg1	VIId					1906:1909	NDV genotype VIId	1893:1909	NDV genotype VIId	1893:1909	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	12	66	theme	VIId	1906:1909	arg1	gene					1885:1888	sequence F gene	1874:1888	sequence F gene of NDV genotype VIId	1874:1909	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	2	67	from	flocks	411:416	arg1	samples					378:384	samples	378:384	samples from seven suspected NDV flocks of vaccinated chickens	378:439	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	8	68	theme	glycosylation	1282:1294	arg1	sites					1296:1300	six potential N-linked glycosylation sites	1259:1300	six potential N-linked glycosylation sites	1259:1300	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	4	69	dep	1.73	751:754	arg1	to					748:749	to	748:749	to	748:749	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	12	70	theme	sequence	1874:1881	arg1	gene					1885:1888	sequence F gene	1874:1888	sequence F gene of NDV genotype VIId	1874:1909	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	1	71	from	sequence	187:194	arg1	regard					232:237	regard	232:237	regard to pathotyping and genotyping	232:267	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	8	72	theme	sequenced	1235:1243	arg1	isolates					1245:1252	seven sequenced isolates	1229:1252	seven sequenced isolates	1229:1252	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	7	73	theme	genotype	1121:1128	arg1	VIId					1130:1133	genotype VIId	1121:1133	genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains	1121:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
30147262	5	74	theme	F	897:897	arg1	gene					899:902	full-length F gene	885:902	full-length F gene	885:902	Pathotyping and genotyping of these isolates were done through sequencing of full-length F gene.
30147262	5	75	theme	isolates	844:851	arg1	Pathotyping					808:818	Pathotyping	808:818	Pathotyping	808:818	Pathotyping and genotyping of these isolates were done through sequencing of full-length F gene.
30147262	5	75	theme	isolates	844:851	arg1	genotyping					824:833	genotyping	824:833	genotyping	824:833	Pathotyping and genotyping of these isolates were done through sequencing of full-length F gene.
30147262	11	76	theme	amino	1682:1686	arg1	substitutions					1693:1705	52 amino acid substitutions	1679:1705	52 amino acid substitutions within fusion gene	1679:1724	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	11	77	from	viruses	1652:1658	arg1	study					1668:1672	this study	1663:1672	this study	1663:1672	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	8	78	theme	potential	1263:1271	arg1	sites					1296:1300	six potential N-linked glycosylation sites	1259:1300	six potential N-linked glycosylation sites	1259:1300	Six of seven sequenced isolates have six potential N-linked glycosylation sites.
30147262	0	79	theme	disease	67:73	arg1	virus					75:79	Newcastle disease virus	57:79	Newcastle disease virus genotype VIId	57:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	12	80	theme	important	1856:1864	arg1	need					1866:1869	the important need	1852:1869	the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt	1852:1959	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	6	81	theme	site	982:985	arg1	112RRQKRF117					994:1005	112RRQKRF117	994:1005	112RRQKRF117	994:1005	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	6	81	theme	site	982:985	arg1	motif					987:991	characteristic cleavage site motif	958:991	characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV	958:1039	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	2	82	theme	NDV	407:409	arg1	flocks					411:416	seven suspected NDV flocks	391:416	seven suspected NDV flocks of vaccinated chickens	391:439	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	4	83	theme	NDV	653:655	arg1	isolates					657:664	the NDV isolates	649:664	the NDV isolates	649:664	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	11	84	theme	fusion	1714:1719	arg1	gene					1721:1724	fusion gene	1714:1724	fusion gene	1714:1724	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	0	85	theme	genotype	81:88	arg1	VIId					90:93	Newcastle disease virus genotype VIId	57:93	Newcastle disease virus genotype VIId	57:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	6	86	theme	characteristic	958:971	arg1	112RRQKRF117					994:1005	112RRQKRF117	994:1005	112RRQKRF117	994:1005	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	6	86	theme	characteristic	958:971	arg1	motif					987:991	characteristic cleavage site motif	958:991	characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV	958:1039	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	12	87	theme	present	1828:1834	arg1	work					1836:1839	The present work	1824:1839	The present work	1824:1839	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	2	88	theme	chickens	432:439	arg1	flocks					411:416	seven suspected NDV flocks	391:416	seven suspected NDV flocks of vaccinated chickens	391:439	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	3	89	from	inoculation	560:570	arg1	eggs					618:621	specific pathogen-free embryonated chicken eggs	575:621	specific pathogen-free embryonated chicken eggs	575:621	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	10	90	theme	at	1576:1577	arg1	residue					1579:1585	cysteine at residue 370	1567:1589	cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016	1567:1634	In all our strains, 10 cysteine residues are recorded, except one loss of cysteine at residue 370 in both NDV-EG-35-2014 and NDV-GHB-328F-2016.
30147262	1	91	theme	NDV	304:306	arg1	evolution					286:294	the evolution	282:294	the evolution of this NDV in Egypt	282:315	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	6	92	theme	NDV	1037:1039	arg1	strains					1026:1032	the velogenic strains	1012:1032	the velogenic strains of NDV	1012:1039	Results indicated that the seven NDV isolates showed characteristic cleavage site motif (112RRQKRF117) for the velogenic strains of NDV.
30147262	4	93	theme	intracerebral	693:705	arg1	index					721:725	intracerebral pathogenicity index	693:725	intracerebral pathogenicity index	693:725	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	0	94	theme	full	30:33	arg1	protein					42:48	full fusion protein	30:48	full fusion protein (F) of Newcastle disease virus genotype VIId	30:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	0	94	theme	full	30:33	arg1	F					51:51	F	51:51	F	51:51	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	3	95	theme	embryonated	598:608	arg1	eggs					618:621	specific pathogen-free embryonated chicken eggs	575:621	specific pathogen-free embryonated chicken eggs	575:621	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	1	96	dep	AIM	133:135	arg1	was					158:160	was	158:160	was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt	158:315	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	0	97	theme	protein	42:48	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId	0:93	Molecular characterization of full fusion protein (F) of Newcastle disease virus genotype VIId isolated from Egypt during 2012-2016.
30147262	3	98	theme	specific	575:582	arg1	eggs					618:621	specific pathogen-free embryonated chicken eggs	575:621	specific pathogen-free embryonated chicken eggs	575:621	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	4	99	theme	velogenic	776:784	arg1	type					786:789	the velogenic type	772:789	the velogenic type of NDV isolates	772:805	RESULTS Pathogenicity of the NDV isolates has been estimated through intracerebral pathogenicity index and ranged from 1.66 to 1.73 which indicates the velogenic type of NDV isolates.
30147262	11	100	theme	antigenic	1789:1797	arg1	function					1814:1821	its antigenic and structural function	1785:1821	its antigenic and structural function	1785:1821	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	9	101	theme	antigenic	1342:1350	arg1	fusion					1361:1366	fusion	1361:1366	fusion	1361:1366	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	9	101	theme	antigenic	1342:1350	arg1	sites					1352:1356	the five antigenic sites	1333:1356	the five antigenic sites of fusion	1333:1366	The neutralization epitope on the five antigenic sites of fusion is conserved in all Egyptian strains of this study except NDV-KFR-B7-2012 which has a substitution at D 170 N in epitope A4.
30147262	3	102	theme	pathological	529:540	arg1	specimens					542:550	pathological specimens	529:550	pathological specimens	529:550	The NDV was successfully isolated from pathological specimens through inoculation in specific pathogen-free embryonated chicken eggs.
30147262	2	103	from	governorates	467:478	arg1	Egypt					483:487	Egypt	483:487	Egypt	483:487	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	2	103	from	governorates	467:478	arg1	2012-2016					448:456	2012-2016	448:456	2012-2016 from six governorates in Egypt	448:487	MATERIALS AND METHODS The present study was conducted using samples from seven suspected NDV flocks of vaccinated chickens during 2012-2016 from six governorates in Egypt.
30147262	11	104	theme	All	1648:1650	arg1	viruses					1652:1658	CONCLUSION All viruses	1637:1658	CONCLUSION All viruses in this study	1637:1672	CONCLUSION All viruses in this study have 52 amino acid substitutions within fusion gene in compared with Lasota strain that reveals importance for its antigenic and structural function.
30147262	1	105	theme	gene	182:185	arg1	sequence					187:194	the full F gene sequence	171:194	the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping	171:267	AIM The aim of this work was to study the full F gene sequence of Newcastle disease virus (NDV) in regard to pathotyping and genotyping and to study the evolution of this NDV in Egypt.
30147262	12	106	theme	NDV	1948:1950	arg1	evolution					1930:1938	the evolution	1926:1938	the evolution of this NDV in Egypt	1926:1959	The present work highlights the important need to sequence F gene of NDV genotype VIId to investigate the evolution of this NDV in Egypt.
30147262	7	107	theme	East	1208:1211	arg1	strains					1213:1219	the Middle East strains	1197:1219	the Middle East strains	1197:1219	Phylogenetic analysis of the F gene clustered these isolates within Group I of genotype VIId within Israeli strains NDV/IS/2015, NDV-Ch/SD883, and most of the Middle East strains.
29321565	0	0	theme	Cordyceps	112:120	arg1	militaris					122:130	Cordyceps militaris	112:130	Cordyceps militaris	112:130	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	3	1	theme	ribosomal	750:758	arg1	RNA					760:762	16S ribosomal RNA	746:762	16S ribosomal RNA gene analysis	746:776	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	7	2	theme	Cordyceps	1305:1313	arg1	militaris					1315:1323	Cordyceps militaris	1305:1323	Cordyceps militaris	1305:1323	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	5	3	theme	fucose-containing	1018:1034	arg1	activity					1069:1076	fucose-containing oligosaccharides-specific ENGase activity	1018:1076	fucose-containing oligosaccharides-specific ENGase activity	1018:1076	Recombinant proteins, purified from Escherichia coli expressing candidate genes ORF1152, ORF1188, ORF3046 and ORF3750 exhibited fucose-containing oligosaccharides-specific ENGase activity.
29321565	8	4	theme	ENGases	1620:1626	arg1	specificity					1593:1603	the substrate specificity	1579:1603	the substrate specificity of these novel ENGases	1579:1626	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	7	5	theme	candidate	1203:1211	arg1	genes					1213:1217	these candidate genes	1197:1217	these candidate genes	1197:1217	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	5	6	theme	candidate	954:962	arg1	genes					964:968	candidate genes ORF1152, ORF1188, ORF3046 and ORF3750	954:1006	candidate genes ORF1152, ORF1188, ORF3046 and ORF3750	954:1006	Recombinant proteins, purified from Escherichia coli expressing candidate genes ORF1152, ORF1188, ORF3046 and ORF3750 exhibited fucose-containing oligosaccharides-specific ENGase activity.
29321565	0	7	from	Characterization	0:15	arg1	species					80:86	Sphingobacterium species	63:86	Sphingobacterium species	63:86	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	0	7	from	Characterization	0:15	arg1	bassiana					99:106	Beauveria bassiana	89:106	Beauveria bassiana	89:106	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	0	7	from	Characterization	0:15	arg1	militaris					122:130	Cordyceps militaris	112:130	Cordyceps militaris	112:130	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	7	8	from	militaris	1315:1323	arg1	ORF1188					1253:1259	ORF1188	1253:1259	ORF1188	1253:1259	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	7	8	from	militaris	1315:1323	arg1	other					1296:1300	other	1296:1300	other	1296:1300	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	6	9	theme	acidic	1130:1135	arg1	pHs					1137:1139	very acidic pHs	1125:1139	very acidic pHs	1125:1139	These ENGases exhibited optimum activities at very acidic pHs (between pH 2.3-2.5).
29321565	1	10	link	N-linked	274:281	arg1	oligosaccharides					283:298	N-linked oligosaccharides	274:298	N-linked oligosaccharides	274:298	Endo-β-N-acetylglucosaminidase (ENGase) catalyzes hydrolysis of N-linked oligosaccharides.
29321565	3	11	theme	ENGase	613:618	arg1	activity					620:627	ENGase activity	613:627	ENGase activity	613:627	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	0	12	from	species	80:86	arg1	Characterization					0:15	Characterization	0:15	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.	0:208	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	0	12	from	species	80:86	arg1	endo-β-N-acetylglucosaminidases					26:56	novel endo-β-N-acetylglucosaminidases	20:56	novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG	20:207	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	4	13	theme	strain	882:887	arg1	genome					867:872	the genome	863:872	the genome of this strain	863:887	By draft genome sequencing, five candidate ENGase encoding genes were identified in the genome of this strain.
29321565	8	14	theme	ORF1188	1338:1344	arg1	ENGases					1371:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases	1326:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases	1326:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	4	15	theme	ENGase	822:827	arg1	genes					838:842	five candidate ENGase encoding genes	807:842	five candidate ENGase encoding genes	807:842	By draft genome sequencing, five candidate ENGase encoding genes were identified in the genome of this strain.
29321565	8	16	theme	substrate	1583:1591	arg1	specificity					1593:1603	the substrate specificity	1579:1603	the substrate specificity of these novel ENGases	1579:1626	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	3	17	theme	RNA	760:762	arg1	analysis					769:776	16S ribosomal RNA gene analysis	746:776	16S ribosomal RNA gene analysis	746:776	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	8	18	theme	immunoglobulin	1452:1465	arg1	rituximab					1441:1449	rituximab	1441:1449	rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates	1441:1698	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	8	18	theme	immunoglobulin	1452:1465	arg1	G					1467:1467	immunoglobulin G	1452:1467	immunoglobulin G	1452:1467	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	4	19	theme	candidate	812:820	arg1	genes					838:842	five candidate ENGase encoding genes	807:842	five candidate ENGase encoding genes	807:842	By draft genome sequencing, five candidate ENGase encoding genes were identified in the genome of this strain.
29321565	8	20	gly	glycoproteins	1660:1672	arg1	glycoproteins					1660:1672	natural glycoproteins	1652:1672	natural glycoproteins	1652:1672	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	7	21	theme	ORF1188	1253:1259	arg1	homologs					1241:1248	two fungal homologs	1230:1248	two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris	1230:1323	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	3	22	theme	gene	764:767	arg1	analysis					769:776	16S ribosomal RNA gene analysis	746:776	16S ribosomal RNA gene analysis	746:776	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	4	23	theme	draft	782:786	arg1	sequencing					795:804	draft genome sequencing	782:804	draft genome sequencing	782:804	By draft genome sequencing, five candidate ENGase encoding genes were identified in the genome of this strain.
29321565	6	24	dep	exhibited	1093:1101	arg1	pH					1150:1151	pH 2.3-2.5	1150:1159	pH 2.3-2.5	1150:1159	These ENGases exhibited optimum activities at very acidic pHs (between pH 2.3-2.5).
29321565	8	25	theme	Recombinant	1326:1336	arg1	ORF1188					1338:1344	Recombinant ORF1188	1326:1344	Recombinant ORF1188	1326:1344	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	3	26	theme	soil	487:490	arg1	samples					492:498	soil samples	487:498	soil samples	487:498	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	7	27	theme	BLAST	1163:1167	arg1	searches					1169:1176	BLAST searches	1163:1176	BLAST searches using sequences of these candidate genes	1163:1217	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	3	28	theme	culture	636:642	arg1	supernatant					644:654	the culture supernatant	632:654	the culture supernatant	632:654	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	0	29	theme	endo-β-N-acetylglucosaminidases	26:56	arg1	Characterization					0:15	Characterization	0:15	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.	0:208	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	8	30	theme	natural	1652:1658	arg1	glycoproteins					1660:1672	natural glycoproteins	1652:1672	natural glycoproteins	1652:1672	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	2	31	theme	fucose-containing	381:397	arg1	ENGase					425:430	no fucose-containing oligosaccharides-specific ENGase	378:430	no fucose-containing oligosaccharides-specific ENGase	378:430	Although many ENGases have been characterized from various organisms, so far no fucose-containing oligosaccharides-specific ENGase has been identified in any organism.
29321565	2	32	theme	oligosaccharides-specific	399:423	arg1	ENGase					425:430	no fucose-containing oligosaccharides-specific ENGase	378:430	no fucose-containing oligosaccharides-specific ENGase	378:430	Although many ENGases have been characterized from various organisms, so far no fucose-containing oligosaccharides-specific ENGase has been identified in any organism.
29321565	0	33	theme	fucose-containing	160:176	arg1	oligosaccharides					178:193	fucose-containing oligosaccharides	160:193	fucose-containing oligosaccharides	160:193	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	7	34	from	one	1262:1264	arg1	bassiana					1279:1286	Beauveria bassiana	1269:1286	Beauveria bassiana	1269:1286	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	4	35	theme	genome	788:793	arg1	sequencing					795:804	draft genome sequencing	782:804	draft genome sequencing	782:804	By draft genome sequencing, five candidate ENGase encoding genes were identified in the genome of this strain.
29321565	8	36	from	B	1543:1543	arg1	residues					1523:1530	the high-mannose-containing oligosaccharides residues	1478:1530	rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates	1441:1698	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	1	37	theme	N-linked	274:281	arg1	oligosaccharides					283:298	N-linked oligosaccharides	274:298	N-linked oligosaccharides	274:298	Endo-β-N-acetylglucosaminidase (ENGase) catalyzes hydrolysis of N-linked oligosaccharides.
29321565	0	38	theme	Sphingobacterium	63:78	arg1	species					80:86	Sphingobacterium species	63:86	Sphingobacterium species	63:86	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	0	39	theme	human	199:203	arg1	IgG					205:207	human IgG	199:207	human IgG	199:207	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	3	40	theme	-labeled	528:535	arg1	sialylglycan					537:548	dansyl chloride (Dns)-labeled sialylglycan	507:548	dansyl chloride (Dns)-labeled sialylglycan (Dns-SG)	507:557	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	3	40	theme	-labeled	528:535	arg1	substrate					564:572	a substrate	562:572	a substrate	562:572	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	3	40	theme	-labeled	528:535	arg1	Dns-SG					551:556	Dns-SG	551:556	Dns-SG	551:556	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	8	41	theme	oligosaccharides	1506:1521	arg1	residues					1523:1530	the high-mannose-containing oligosaccharides residues	1478:1530	rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates	1441:1698	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	1	42	theme	oligosaccharides	283:298	arg1	hydrolysis					260:269	hydrolysis	260:269	hydrolysis of N-linked oligosaccharides	260:298	Endo-β-N-acetylglucosaminidase (ENGase) catalyzes hydrolysis of N-linked oligosaccharides.
29321565	7	43	theme	fungal	1234:1239	arg1	homologs					1241:1248	two fungal homologs	1230:1248	two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris	1230:1323	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	0	44	from	bassiana	99:106	arg1	Characterization					0:15	Characterization	0:15	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.	0:208	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	0	44	from	bassiana	99:106	arg1	endo-β-N-acetylglucosaminidases					26:56	novel endo-β-N-acetylglucosaminidases	20:56	novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG	20:207	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	8	45	theme	high-mannose-containing	1482:1504	arg1	residues					1523:1530	the high-mannose-containing oligosaccharides residues	1478:1530	rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates	1441:1698	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	5	46	theme	Recombinant	890:900	arg1	proteins					902:909	Recombinant proteins	890:909	Recombinant proteins	890:909	Recombinant proteins, purified from Escherichia coli expressing candidate genes ORF1152, ORF1188, ORF3046 and ORF3750 exhibited fucose-containing oligosaccharides-specific ENGase activity.
29321565	7	47	theme	genes	1213:1217	arg1	sequences					1184:1192	sequences	1184:1192	sequences of these candidate genes	1184:1217	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	5	48	theme	oligosaccharides-specific	1036:1060	arg1	activity					1069:1076	fucose-containing oligosaccharides-specific ENGase activity	1018:1076	fucose-containing oligosaccharides-specific ENGase activity	1018:1076	Recombinant proteins, purified from Escherichia coli expressing candidate genes ORF1152, ORF1188, ORF3046 and ORF3750 exhibited fucose-containing oligosaccharides-specific ENGase activity.
29321565	2	49	theme	many	310:313	arg1	ENGases					315:321	many ENGases	310:321	many ENGases	310:321	Although many ENGases have been characterized from various organisms, so far no fucose-containing oligosaccharides-specific ENGase has been identified in any organism.
29321565	8	50	theme	novel	1614:1618	arg1	ENGases					1620:1626	these novel ENGases	1608:1626	these novel ENGases	1608:1626	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	8	51	theme	Cordyceps	1361:1369	arg1	ENGases					1371:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases	1326:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases	1326:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	3	52	theme	Sphingobacterium	718:733	arg1	species					735:741	a Sphingobacterium species	716:741	a Sphingobacterium species	716:741	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	3	52	theme	Sphingobacterium	718:733	arg1	strain					662:667	this strain	657:667	this strain	657:667	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	2	53	theme	various	352:358	arg1	organisms					360:368	various organisms	352:368	various organisms	352:368	Although many ENGases have been characterized from various organisms, so far no fucose-containing oligosaccharides-specific ENGase has been identified in any organism.
29321565	8	54	theme	Beauveria	1347:1355	arg1	ENGases					1371:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases	1326:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases	1326:1377	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	5	55	theme	ENGase	1062:1067	arg1	activity					1069:1076	fucose-containing oligosaccharides-specific ENGase activity	1018:1076	fucose-containing oligosaccharides-specific ENGase activity	1018:1076	Recombinant proteins, purified from Escherichia coli expressing candidate genes ORF1152, ORF1188, ORF3046 and ORF3750 exhibited fucose-containing oligosaccharides-specific ENGase activity.
29321565	7	56	from	other	1296:1300	arg1	militaris					1315:1323	Cordyceps militaris	1305:1323	Cordyceps militaris	1305:1323	BLAST searches using sequences of these candidate genes identified two fungal homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps militaris.
29321565	4	57	theme	encoding	829:836	arg1	genes					838:842	five candidate ENGase encoding genes	807:842	five candidate ENGase encoding genes	807:842	By draft genome sequencing, five candidate ENGase encoding genes were identified in the genome of this strain.
29321565	8	58	theme	RNase	1537:1541	arg1	B					1543:1543	RNase B	1537:1543	RNase B	1537:1543	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	8	58	theme	RNase	1537:1541	arg1	result					1548:1553	a result	1546:1553	a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates	1546:1698	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	0	59	from	militaris	122:130	arg1	Characterization					0:15	Characterization	0:15	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.	0:208	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	0	59	from	militaris	122:130	arg1	endo-β-N-acetylglucosaminidases					26:56	novel endo-β-N-acetylglucosaminidases	20:56	novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG	20:207	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	8	60	theme	oligosaccharides	1410:1425	arg1	residues					1427:1434	the fucose-containing oligosaccharides residues	1388:1434	the fucose-containing oligosaccharides residues	1388:1434	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
29321565	6	61	theme	optimum	1103:1109	arg1	activities					1111:1120	optimum activities	1103:1120	optimum activities	1103:1120	These ENGases exhibited optimum activities at very acidic pHs (between pH 2.3-2.5).
29321565	0	62	theme	Beauveria	89:97	arg1	bassiana					99:106	Beauveria bassiana	89:106	Beauveria bassiana	89:106	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	3	63	theme	16S	746:748	arg1	RNA					760:762	16S ribosomal RNA	746:762	16S ribosomal RNA gene analysis	746:776	Here, we screened soil samples, using dansyl chloride (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that exhibits ENGase activity in the culture supernatant; this strain, named here as strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA gene analysis.
29321565	0	64	theme	novel	20:24	arg1	endo-β-N-acetylglucosaminidases					26:56	novel endo-β-N-acetylglucosaminidases	20:56	novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG	20:207	Characterization of novel endo-β-N-acetylglucosaminidases from Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that specifically hydrolyze fucose-containing oligosaccharides and human IgG.
29321565	8	65	theme	fucose-containing	1392:1408	arg1	residues					1427:1434	the fucose-containing oligosaccharides residues	1388:1434	the fucose-containing oligosaccharides residues	1388:1434	Recombinant ORF1188, Beauveria and Cordyceps ENGases released the fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but not the high-mannose-containing oligosaccharides residues from RNase B, a result that not only confirmed the substrate specificity of these novel ENGases but also suggested that natural glycoproteins could be their substrates.
31816088	8	0	theme	transparent	1346:1356	arg1	research					1375:1382	transparent and reproducible research	1346:1382	transparent and reproducible research	1346:1382	By providing the entire analysis history online, we highlight how the Galaxy framework fosters transparent and reproducible research.
31816088	4	1	theme	mass	714:717	arg1	tools					740:744	18 dedicated mass spectrometry imaging tools	701:744	18 dedicated mass spectrometry imaging tools	701:744	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	4	2	theme	imaging	732:738	arg1	tools					740:744	18 dedicated mass spectrometry imaging tools	701:744	18 dedicated mass spectrometry imaging tools	701:744	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	1	3	theme	analytes	258:265	arg1	hundreds					246:253	hundreds	246:253	hundreds of analytes	246:265	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	9	4	dep	CONCLUSION	1385:1394	arg1	emerged					1421:1427	emerged	1421:1427	has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency	1417:1579	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	3	5	theme	reproducible	527:538	arg1	analysis					545:552	reproducible data analysis	527:552	reproducible data analysis	527:552	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	7	6	theme	N-linked	1218:1225	arg1	glycan					1227:1232	a publicly available N-linked glycan	1197:1232	a publicly available N-linked glycan imaging dataset	1197:1248	To demonstrate the utility of our tools, we re-analyzed a publicly available N-linked glycan imaging dataset.
31816088	4	7	theme	transparent	811:821	arg1	analysis					828:835	accessible, reproducible, and transparent data analysis	781:835	accessible, reproducible, and transparent data analysis	781:835	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	6	8	from	material	1086:1093	arg1	metabolomics					1127:1138	metabolomics	1127:1138	metabolomics	1127:1138	Furthermore, we created hands-on training material for use cases in proteomics and metabolomics.
31816088	6	8	from	material	1086:1093	arg1	proteomics					1112:1121	proteomics	1112:1121	proteomics	1112:1121	Furthermore, we created hands-on training material for use cases in proteomics and metabolomics.
31816088	3	9	theme	programming	568:578	arg1	skills					580:585	programming skills	568:585	programming skills	568:585	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	5	10	theme	quality	948:954	arg1	control					956:962	quality control	948:962	quality control	948:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	0	11	from	analysis	59:66	arg1	Galaxy					71:76	Galaxy	71:76	Galaxy	71:76	Accessible and reproducible mass spectrometry imaging data analysis in Galaxy.
31816088	8	12	theme	reproducible	1362:1373	arg1	research					1375:1382	transparent and reproducible research	1346:1382	transparent and reproducible research	1346:1382	By providing the entire analysis history online, we highlight how the Galaxy framework fosters transparent and reproducible research.
31816088	5	13	theme	major	915:919	arg1	steps					934:938	all major MSI analysis steps	911:938	all major MSI analysis steps such as quality control	911:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	13	theme	major	915:919	arg1	preprocessing					980:992	preprocessing	980:992	preprocessing	980:992	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	13	theme	major	915:919	arg1	co-registration					1027:1041	image co-registration	1021:1041	image co-registration	1021:1041	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	13	theme	major	915:919	arg1	control					956:962	quality control	948:962	quality control	948:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	13	theme	major	915:919	arg1	analysis					1007:1014	statistical analysis	995:1014	statistical analysis	995:1014	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	13	theme	major	915:919	arg1	visualization					965:977	visualization	965:977	visualization	965:977	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	2	14	theme	imaging	334:340	arg1	interface					293:301	the interface	289:301	the interface of proteomics/metabolomics and imaging	289:340	Being at the interface of proteomics/metabolomics and imaging, the acquired datasets are large and complex and often analyzed with proprietary software or in-house scripts, which hinders reproducibility.
31816088	5	15	theme	analysis	925:932	arg1	steps					934:938	all major MSI analysis steps	911:938	all major MSI analysis steps such as quality control	911:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	15	theme	analysis	925:932	arg1	preprocessing					980:992	preprocessing	980:992	preprocessing	980:992	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	15	theme	analysis	925:932	arg1	co-registration					1027:1041	image co-registration	1021:1041	image co-registration	1021:1041	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	15	theme	analysis	925:932	arg1	control					956:962	quality control	948:962	quality control	948:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	15	theme	analysis	925:932	arg1	analysis					1007:1014	statistical analysis	995:1014	statistical analysis	995:1014	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	15	theme	analysis	925:932	arg1	visualization					965:977	visualization	965:977	visualization	965:977	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	6	16	theme	hands-on	1068:1075	arg1	material					1086:1093	hands-on training material	1068:1093	hands-on training material for use cases in proteomics and metabolomics	1068:1138	Furthermore, we created hands-on training material for use cases in proteomics and metabolomics.
31816088	7	17	link	N-linked	1218:1225	arg1	glycan					1227:1232	a publicly available N-linked glycan	1197:1232	a publicly available N-linked glycan imaging dataset	1197:1248	To demonstrate the utility of our tools, we re-analyzed a publicly available N-linked glycan imaging dataset.
31816088	9	18	theme	MSI	1481:1483	arg1	data					1485:1488	MSI data	1481:1488	MSI data	1481:1488	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	7	19	theme	available	1208:1216	arg1	glycan					1227:1232	a publicly available N-linked glycan	1197:1232	a publicly available N-linked glycan imaging dataset	1197:1248	To demonstrate the utility of our tools, we re-analyzed a publicly available N-linked glycan imaging dataset.
31816088	5	20	theme	MSI	921:923	arg1	steps					934:938	all major MSI analysis steps	911:938	all major MSI analysis steps such as quality control	911:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	20	theme	MSI	921:923	arg1	preprocessing					980:992	preprocessing	980:992	preprocessing	980:992	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	20	theme	MSI	921:923	arg1	co-registration					1027:1041	image co-registration	1021:1041	image co-registration	1021:1041	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	20	theme	MSI	921:923	arg1	control					956:962	quality control	948:962	quality control	948:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	20	theme	MSI	921:923	arg1	analysis					1007:1014	statistical analysis	995:1014	statistical analysis	995:1014	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	20	theme	MSI	921:923	arg1	visualization					965:977	visualization	965:977	visualization	965:977	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	9	21	theme	analysis	1443:1450	arg1	platform					1452:1459	a powerful analysis platform	1432:1459	a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency	1432:1579	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	1	22	theme	BACKGROUND	79:88	arg1	spectrometry					95:106	BACKGROUND Mass spectrometry	79:106	BACKGROUND Mass spectrometry imaging	79:114	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	6	23	theme	use	1099:1101	arg1	cases					1103:1107	use cases	1099:1107	use cases	1099:1107	Furthermore, we created hands-on training material for use cases in proteomics and metabolomics.
31816088	2	24	theme	proteomics/metabolomics	306:328	arg1	interface					293:301	the interface	289:301	the interface of proteomics/metabolomics and imaging	289:340	Being at the interface of proteomics/metabolomics and imaging, the acquired datasets are large and complex and often analyzed with proprietary software or in-house scripts, which hinders reproducibility.
31816088	1	25	theme	Mass	90:93	arg1	spectrometry					95:106	BACKGROUND Mass spectrometry	79:106	BACKGROUND Mass spectrometry imaging	79:114	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	8	26	theme	analysis	1275:1282	arg1	online					1292:1297	the entire analysis history online	1264:1297	the entire analysis history online	1264:1297	By providing the entire analysis history online, we highlight how the Galaxy framework fosters transparent and reproducible research.
31816088	0	27	theme	Accessible	0:9	arg1	data					54:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data analysis in Galaxy.
31816088	1	28	theme	spectrometry	95:106	arg1	imaging					108:114	BACKGROUND Mass spectrometry imaging	79:114	BACKGROUND Mass spectrometry imaging	79:114	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	8	29	theme	history	1284:1290	arg1	online					1292:1297	the entire analysis history online	1264:1297	the entire analysis history online	1264:1297	By providing the entire analysis history online, we highlight how the Galaxy framework fosters transparent and reproducible research.
31816088	8	30	theme	entire	1268:1273	arg1	online					1292:1297	the entire analysis history online	1264:1297	the entire analysis history online	1264:1297	By providing the entire analysis history online, we highlight how the Galaxy framework fosters transparent and reproducible research.
31816088	0	31	theme	mass	28:31	arg1	data					54:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data analysis in Galaxy.
31816088	8	32	theme	Galaxy	1321:1326	arg1	framework					1328:1336	the Galaxy framework	1317:1336	the Galaxy framework	1317:1336	By providing the entire analysis history online, we highlight how the Galaxy framework fosters transparent and reproducible research.
31816088	1	33	used	used	132:135	arg2	imaging					108:114	BACKGROUND Mass spectrometry imaging	79:114	BACKGROUND Mass spectrometry imaging	79:114	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	4	34	dep	FINDINGS	673:680	arg1	integrated					690:699	integrated	690:699	have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis	685:835	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	6	35	theme	training	1077:1084	arg1	material					1086:1093	hands-on training material	1068:1093	hands-on training material for use cases in proteomics and metabolomics	1068:1138	Furthermore, we created hands-on training material for use cases in proteomics and metabolomics.
31816088	2	36	theme	in-house	435:442	arg1	scripts					444:450	in-house scripts	435:450	in-house scripts	435:450	Being at the interface of proteomics/metabolomics and imaging, the acquired datasets are large and complex and often analyzed with proprietary software or in-house scripts, which hinders reproducibility.
31816088	9	37	theme	transparency	1568:1579	arg1	levels					1538:1543	high levels	1533:1543	high levels of reproducibility and transparency	1533:1579	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	4	38	theme	spectrometry	719:730	arg1	tools					740:744	18 dedicated mass spectrometry imaging tools	701:744	18 dedicated mass spectrometry imaging tools	701:744	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	3	39	theme	Open	484:487	arg1	solutions					505:513	Open source software solutions	484:513	Open source software solutions that enable reproducible data analysis	484:552	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	0	40	theme	imaging	46:52	arg1	data					54:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data analysis in Galaxy.
31816088	5	41	theme	image	1021:1025	arg1	steps					934:938	all major MSI analysis steps	911:938	all major MSI analysis steps such as quality control	911:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	41	theme	image	1021:1025	arg1	control					956:962	quality control	948:962	quality control	948:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	41	theme	image	1021:1025	arg1	co-registration					1027:1041	image co-registration	1021:1041	image co-registration	1021:1041	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	3	42	theme	many	623:626	arg1	researchers					660:670	many mass spectrometry imaging (MSI) researchers	623:670	many mass spectrometry imaging (MSI) researchers	623:670	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	9	43	theme	data	1485:1488	arg1	analysis					1469:1476	the analysis	1465:1476	the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency	1465:1579	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	2	44	theme	proprietary	411:421	arg1	software					423:430	proprietary software	411:430	proprietary software	411:430	Being at the interface of proteomics/metabolomics and imaging, the acquired datasets are large and complex and often analyzed with proprietary software or in-house scripts, which hinders reproducibility.
31816088	0	45	theme	spectrometry	33:44	arg1	data					54:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data analysis in Galaxy.
31816088	7	46	theme	tools	1175:1179	arg1	utility					1160:1166	the utility	1156:1166	the utility of our tools	1156:1179	To demonstrate the utility of our tools, we re-analyzed a publicly available N-linked glycan imaging dataset.
31816088	1	47	contain	has	189:191	arg1	it					186:187	it	186:187	it	186:187	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	1	47	contain	has	189:191	arg2	ability					197:203	the ability to determine the spatial distribution of hundreds of analytes in a sample	193:277	the ability to determine the spatial distribution of hundreds of analytes in a sample	193:277	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	3	48	theme	mass	628:631	arg1	imaging					646:652	mass spectrometry imaging	628:652	many mass spectrometry imaging (MSI) researchers	623:670	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	3	48	theme	mass	628:631	arg1	MSI					655:657	MSI	655:657	MSI	655:657	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	1	49	theme	spatial	222:228	arg1	distribution					230:241	the spatial distribution	218:241	the spatial distribution of hundreds of analytes in a sample	218:277	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	9	50	theme	Galaxy	1400:1405	arg1	framework					1407:1415	The Galaxy framework	1396:1415	The Galaxy framework	1396:1415	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	9	51	theme	high	1533:1536	arg1	levels					1538:1543	high levels	1533:1543	high levels of reproducibility and transparency	1533:1579	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	9	52	with	analysis	1469:1476	arg1	ease					1495:1498	ease	1495:1498	ease of use and access	1495:1516	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	2	53	theme	acquired	347:354	arg1	large					369:373	large	369:373	large	369:373	Being at the interface of proteomics/metabolomics and imaging, the acquired datasets are large and complex and often analyzed with proprietary software or in-house scripts, which hinders reproducibility.
31816088	2	53	theme	acquired	347:354	arg1	datasets					356:363	the acquired datasets	343:363	the acquired datasets	343:363	Being at the interface of proteomics/metabolomics and imaging, the acquired datasets are large and complex and often analyzed with proprietary software or in-house scripts, which hinders reproducibility.
31816088	9	54	theme	reproducibility	1548:1562	arg1	levels					1538:1543	high levels	1533:1543	high levels of reproducibility and transparency	1533:1579	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	9	55	theme	access	1511:1516	arg1	ease					1495:1498	ease	1495:1498	ease of use and access	1495:1516	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	3	56	theme	imaging	646:652	arg1	researchers					660:670	many mass spectrometry imaging (MSI) researchers	623:670	many mass spectrometry imaging (MSI) researchers	623:670	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	1	57	from	distribution	230:241	arg1	sample					272:277	a sample	270:277	a sample	270:277	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	4	58	theme	data	823:826	arg1	analysis					828:835	accessible, reproducible, and transparent data analysis	781:835	accessible, reproducible, and transparent data analysis	781:835	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	4	59	theme	dedicated	704:712	arg1	tools					740:744	18 dedicated mass spectrometry imaging tools	701:744	18 dedicated mass spectrometry imaging tools	701:744	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	3	60	theme	source	489:494	arg1	solutions					505:513	Open source software solutions	484:513	Open source software solutions that enable reproducible data analysis	484:552	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	4	61	theme	accessible	781:790	arg1	analysis					828:835	accessible, reproducible, and transparent data analysis	781:835	accessible, reproducible, and transparent data analysis	781:835	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	5	62	theme	statistical	995:1005	arg1	steps					934:938	all major MSI analysis steps	911:938	all major MSI analysis steps such as quality control	911:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	62	theme	statistical	995:1005	arg1	analysis					1007:1014	statistical analysis	995:1014	statistical analysis	995:1014	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	5	62	theme	statistical	995:1005	arg1	control					956:962	quality control	948:962	quality control	948:962	Our tools are based on Cardinal, MALDIquant, and scikit-image and enable all major MSI analysis steps such as quality control, visualization, preprocessing, statistical analysis, and image co-registration.
31816088	4	63	theme	reproducible	793:804	arg1	analysis					828:835	accessible, reproducible, and transparent data analysis	781:835	accessible, reproducible, and transparent data analysis	781:835	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	1	64	theme	biological	140:149	arg1	research					169:176	biological and translational research	140:176	biological and translational research	140:176	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	4	65	theme	Galaxy	755:760	arg1	framework					762:770	the Galaxy framework	751:770	the Galaxy framework to allow accessible, reproducible, and transparent data analysis	751:835	FINDINGS We have integrated 18 dedicated mass spectrometry imaging tools into the Galaxy framework to allow accessible, reproducible, and transparent data analysis.
31816088	9	66	theme	use	1503:1505	arg1	ease					1495:1498	ease	1495:1498	ease of use and access	1495:1516	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31816088	3	67	theme	spectrometry	633:644	arg1	imaging					646:652	mass spectrometry imaging	628:652	many mass spectrometry imaging (MSI) researchers	623:670	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	3	67	theme	spectrometry	633:644	arg1	MSI					655:657	MSI	655:657	MSI	655:657	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	3	68	theme	data	540:543	arg1	analysis					545:552	reproducible data analysis	527:552	reproducible data analysis	527:552	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	3	69	theme	software	496:503	arg1	solutions					505:513	Open source software solutions	484:513	Open source software solutions that enable reproducible data analysis	484:552	Open source software solutions that enable reproducible data analysis often require programming skills and are therefore not accessible to many mass spectrometry imaging (MSI) researchers.
31816088	1	70	theme	hundreds	246:253	arg1	distribution					230:241	the spatial distribution	218:241	the spatial distribution of hundreds of analytes in a sample	218:277	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	0	71	theme	reproducible	15:26	arg1	data					54:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data	0:57	Accessible and reproducible mass spectrometry imaging data analysis in Galaxy.
31816088	1	72	theme	translational	155:167	arg1	research					169:176	biological and translational research	140:176	biological and translational research	140:176	BACKGROUND Mass spectrometry imaging is increasingly used in biological and translational research because it has the ability to determine the spatial distribution of hundreds of analytes in a sample.
31816088	9	73	theme	powerful	1434:1441	arg1	platform					1452:1459	a powerful analysis platform	1432:1459	a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency	1432:1579	CONCLUSION The Galaxy framework has emerged as a powerful analysis platform for the analysis of MSI data with ease of use and access, together with high levels of reproducibility and transparency.
31492608	0	0	theme	glucoamylase	84:95	arg1	promoter					102:109	an improved glucoamylase gene promoter	72:109	an improved glucoamylase gene promoter	72:109	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	6	1	theme	amino	1008:1012	arg1	acids					1014:1018	six more amino acids	999:1018	six more amino acids	999:1018	N-terminus of the mature rAoTanBP had six more amino acids than the N-terminus of the mature rAoTanBO.
31492608	1	2	theme	Aspergillus	150:160	arg1	oryzae					162:167	Aspergillus oryzae RIB40	150:173	Aspergillus oryzae RIB40	150:173	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	9	3	link	N-linked	1232:1239	arg1	oligosaccharides					1241:1256	N-linked oligosaccharides	1232:1256	N-linked oligosaccharides	1232:1256	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	0	4	theme	improved	75:82	arg1	promoter					102:109	an improved glucoamylase gene promoter	72:109	an improved glucoamylase gene promoter	72:109	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	0	5	from	production	10:19	arg1	oryzae					59:64	Aspergillus oryzae	47:64	Aspergillus oryzae using an improved glucoamylase gene promoter	47:109	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	3	6	theme	80-100 kDa	526:535	arg1	mass					504:507	a molecular mass	492:507	a molecular mass of approximately 80-100 kDa	492:535	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	5	7	theme	tannase	771:777	arg1	2-8					855:857	2-8	855:857	2-8	855:857	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	5	7	theme	tannase	771:777	arg1	activity					779:786	The tannase activity	767:786	The tannase activity of purified rAoTanBO towards natural and artificial substrates	767:849	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	9	8	contain	had	1258:1260	arg2	effect					1265:1270	no effect	1262:1270	no effect	1262:1270	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	9	8	contain	had	1258:1260	arg1	oligosaccharides					1241:1256	N-linked oligosaccharides	1232:1256	N-linked oligosaccharides	1232:1256	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	1	9	from	oryzae	162:167	arg1	AotanB					137:142	AotanB	137:142	AotanB	137:142	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	1	9	from	oryzae	162:167	arg1	gene					131:134	A tannase-encoding gene	112:134	A tannase-encoding gene	112:134	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	3	10	theme	polyacrylamide	563:576	arg1	electrophoresis					582:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	8	11	theme	higher	1194:1199	arg1	thermostability					1201:1215	higher thermostability	1194:1215	higher thermostability	1194:1215	rAoTanBO was stable up to 60°C and higher thermostability than rAoTanBP.
31492608	0	12	theme	gene	97:100	arg1	promoter					102:109	an improved glucoamylase gene promoter	72:109	an improved glucoamylase gene promoter	72:109	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	9	13	theme	N-linked	1232:1239	arg1	oligosaccharides					1241:1256	N-linked oligosaccharides	1232:1256	N-linked oligosaccharides	1232:1256	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	3	14	theme	gel	578:580	arg1	electrophoresis					582:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	4	15	theme	molecular	618:626	arg1	mass					628:631	a molecular mass	616:631	a molecular mass of 65 kDa	616:641	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	5	16	theme	recombinant	889:899	arg1	enzyme					901:906	the recombinant enzyme	885:906	the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP	885:958	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	8	17	dep	60°C	1185:1188	arg1	up					1179:1180	up	1179:1180	up	1179:1180	rAoTanBO was stable up to 60°C and higher thermostability than rAoTanBP.
31492608	2	18	theme	extracellular	425:437	arg1	tannase					354:360	The recombinant tannase	338:360	The recombinant tannase	338:360	The recombinant tannase, designated as rAoTanBO, was produced efficiently as an active extracellular enzyme.
31492608	2	18	theme	extracellular	425:437	arg1	enzyme					439:444	an active extracellular enzyme	415:444	an active extracellular enzyme	415:444	The recombinant tannase, designated as rAoTanBO, was produced efficiently as an active extracellular enzyme.
31492608	3	19	theme	dodecyl	547:553	arg1	electrophoresis					582:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	4	20	theme	maximum	727:733	arg1	activity					735:742	maximum activity	727:742	maximum activity	727:742	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	5	21	theme	purified	791:798	arg1	rAoTanBO					800:807	purified rAoTanBO	791:807	purified rAoTanBO	791:807	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	5	22	dep	2-8	855:857	arg1	folds					859:863	folds	859:863	folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP	859:958	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	3	23	theme	sulfate	555:561	arg1	electrophoresis					582:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	4	24	theme	Purified	699:706	arg1	rAoTanBO					708:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO	665:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0	665:764	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	9	25	theme	rAoTanBP	1318:1325	arg1	stability					1292:1300	stability	1292:1300	stability	1292:1300	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	9	25	theme	rAoTanBP	1318:1325	arg1	activity					1279:1286	activity	1279:1286	activity	1279:1286	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	4	26	theme	H.	696:697	arg1	rAoTanBO					708:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO	665:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0	665:764	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	0	27	theme	Efficient	0:8	arg1	production					10:19	Efficient production	0:19	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.	0:110	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	4	28	with	treatment	650:658	arg1	rAoTanBO					708:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO	665:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0	665:764	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	7	29	theme	higher	1106:1111	arg1	kcat/Km					1135:1141	kcat/Km	1135:1141	kcat/Km	1135:1141	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	7	29	theme	higher	1106:1111	arg1	efficiency					1123:1132	higher catalytic efficiency	1106:1132	higher catalytic efficiency (kcat/Km)	1106:1142	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	3	30	theme	Purified	447:454	arg1	rAoTanBO					456:463	Purified rAoTanBO	447:463	Purified rAoTanBO	447:463	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	0	31	theme	recombinant	24:34	arg1	tannase					36:42	recombinant tannase	24:42	recombinant tannase	24:42	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	7	32	theme	catalytic	1113:1121	arg1	kcat/Km					1135:1141	kcat/Km	1135:1141	kcat/Km	1135:1141	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	7	32	theme	catalytic	1113:1121	arg1	efficiency					1123:1132	higher catalytic efficiency	1106:1132	higher catalytic efficiency (kcat/Km)	1106:1142	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	7	33	contain	had	1102:1104	arg2	efficiency					1123:1132	higher catalytic efficiency	1106:1132	higher catalytic efficiency (kcat/Km)	1106:1142	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	7	33	contain	had	1102:1104	arg1	rAoTanBO					1093:1100	rAoTanBO	1093:1100	rAoTanBO	1093:1100	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	7	33	contain	had	1102:1104	arg2	kcat/Km					1135:1141	kcat/Km	1135:1141	kcat/Km	1135:1141	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	1	34	theme	A. oryzae	196:204	arg1	mutant					227:232	A. oryzae AOK11 niaD-deficient mutant	196:232	A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142	196:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	1	35	theme	improved	292:299	arg1	promoter					319:326	an improved glucoamylase gene promoter PglaA142	289:335	an improved glucoamylase gene promoter PglaA142	289:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	1	36	theme	AOK11	206:210	arg1	mutant					227:232	A. oryzae AOK11 niaD-deficient mutant	196:232	A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142	196:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	5	37	theme	artificial	829:838	arg1	substrates					840:849	artificial substrates	829:849	artificial substrates	829:849	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	1	38	theme	glucoamylase	301:312	arg1	promoter					319:326	an improved glucoamylase gene promoter PglaA142	289:335	an improved glucoamylase gene promoter PglaA142	289:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	3	39	with	band	482:485	arg1	mass					504:507	a molecular mass	492:507	a molecular mass of approximately 80-100 kDa	492:535	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	1	40	theme	niaD-deficient	212:225	arg1	mutant					227:232	A. oryzae AOK11 niaD-deficient mutant	196:232	A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142	196:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	2	41	theme	active	418:423	arg1	tannase					354:360	The recombinant tannase	338:360	The recombinant tannase	338:360	The recombinant tannase, designated as rAoTanBO, was produced efficiently as an active extracellular enzyme.
31492608	2	41	theme	active	418:423	arg1	enzyme					439:444	an active extracellular enzyme	415:444	an active extracellular enzyme	415:444	The recombinant tannase, designated as rAoTanBO, was produced efficiently as an active extracellular enzyme.
31492608	0	42	theme	tannase	36:42	arg1	production					10:19	Efficient production	0:19	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.	0:110	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	1	43	theme	gene	314:317	arg1	promoter					319:326	an improved glucoamylase gene promoter PglaA142	289:335	an improved glucoamylase gene promoter PglaA142	289:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	5	44	theme	Pichia	920:925	arg1	pastoris					927:934	Pichia pastoris	920:934	Pichia pastoris	920:934	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	1	45	attach	derived	234:240	arg2	mutant					227:232	A. oryzae AOK11 niaD-deficient mutant	196:232	A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142	196:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	1	45	attach	derived	234:240	arg1	strain					261:266	an industrial strain	247:266	an industrial strain under the control of an improved glucoamylase gene promoter PglaA142	247:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	3	46	theme	smeared	474:480	arg1	band					482:485	a smeared band	472:485	a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis	472:596	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	1	47	theme	promoter	319:326	arg1	control					278:284	the control	274:284	the control of an improved glucoamylase gene promoter PglaA142	274:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	4	48	contain	had	612:614	arg2	mass					628:631	a molecular mass	616:631	a molecular mass of 65 kDa	616:641	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	4	48	contain	had	612:614	arg1	rAoTanBO					603:610	The rAoTanBO	599:610	The rAoTanBO	599:610	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	7	49	theme	Kinetic	1064:1070	arg1	analyses					1072:1079	Kinetic analyses	1064:1079	Kinetic analyses	1064:1079	Kinetic analyses showed that rAoTanBO had higher catalytic efficiency (kcat/Km) than rAoTanBP.
31492608	1	50	theme	tannase-encoding	114:129	arg1	AotanB					137:142	AotanB	137:142	AotanB	137:142	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	1	50	theme	tannase-encoding	114:129	arg1	gene					131:134	A tannase-encoding gene	112:134	A tannase-encoding gene	112:134	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
31492608	0	51	theme	Aspergillus	47:57	arg1	oryzae					59:64	Aspergillus oryzae	47:64	Aspergillus oryzae using an improved glucoamylase gene promoter	47:109	Efficient production of recombinant tannase in Aspergillus oryzae using an improved glucoamylase gene promoter.
31492608	6	52	theme	rAoTanBP	986:993	arg1	N-terminus					961:970	N-terminus	961:970	N-terminus of the mature rAoTanBP	961:993	N-terminus of the mature rAoTanBP had six more amino acids than the N-terminus of the mature rAoTanBO.
31492608	3	53	from	band	482:485	arg1	electrophoresis					582:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	6	54	theme	mature	979:984	arg1	rAoTanBP					986:993	the mature rAoTanBP	975:993	the mature rAoTanBP	975:993	N-terminus of the mature rAoTanBP had six more amino acids than the N-terminus of the mature rAoTanBO.
31492608	9	55	theme	rAoTanBO	1305:1312	arg1	stability					1292:1300	stability	1292:1300	stability	1292:1300	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	9	55	theme	rAoTanBO	1305:1312	arg1	activity					1279:1286	activity	1279:1286	activity	1279:1286	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	2	56	theme	recombinant	342:352	arg1	tannase					354:360	The recombinant tannase	338:360	The recombinant tannase	338:360	The recombinant tannase, designated as rAoTanBO, was produced efficiently as an active extracellular enzyme.
31492608	2	56	theme	recombinant	342:352	arg1	enzyme					439:444	an active extracellular enzyme	415:444	an active extracellular enzyme	415:444	The recombinant tannase, designated as rAoTanBO, was produced efficiently as an active extracellular enzyme.
31492608	4	57	theme	65 kDa	636:641	arg1	mass					628:631	a molecular mass	616:631	a molecular mass of 65 kDa	616:641	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	9	58	dep	activity	1279:1286	arg1	the					1275:1277	the	1275:1277	the	1275:1277	N-linked oligosaccharides had no effect on the activity and stability of rAoTanBO and rAoTanBP.
31492608	3	59	theme	molecular	494:502	arg1	mass					504:507	a molecular mass	492:507	a molecular mass of approximately 80-100 kDa	492:535	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	5	60	theme	rAoTanBO	800:807	arg1	2-8					855:857	2-8	855:857	2-8	855:857	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	5	60	theme	rAoTanBO	800:807	arg1	activity					779:786	The tannase activity	767:786	The tannase activity of purified rAoTanBO towards natural and artificial substrates	767:849	The tannase activity of purified rAoTanBO towards natural and artificial substrates was 2-8 folds higher than that of the recombinant enzyme produced by Pichia pastoris, designated as rAoTanBP.
31492608	4	61	theme	endo-β-N-acetylglucosaminidase	665:694	arg1	rAoTanBO					708:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO	665:715	endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0	665:764	The rAoTanBO had a molecular mass of 65 kDa, after treatment with endo-β-N-acetylglucosaminidase H. Purified rAoTanBO exhibited maximum activity at 30-35°C and pH 6.0.
31492608	6	62	contain	had	995:997	arg1	N-terminus					961:970	N-terminus	961:970	N-terminus of the mature rAoTanBP	961:993	N-terminus of the mature rAoTanBP had six more amino acids than the N-terminus of the mature rAoTanBO.
31492608	6	62	contain	had	995:997	arg2	acids					1014:1018	six more amino acids	999:1018	six more amino acids	999:1018	N-terminus of the mature rAoTanBP had six more amino acids than the N-terminus of the mature rAoTanBO.
31492608	6	63	theme	rAoTanBO	1054:1061	arg1	N-terminus					1029:1038	the N-terminus	1025:1038	the N-terminus of the mature rAoTanBO	1025:1061	N-terminus of the mature rAoTanBP had six more amino acids than the N-terminus of the mature rAoTanBO.
31492608	6	64	theme	mature	1047:1052	arg1	rAoTanBO					1054:1061	the mature rAoTanBO	1043:1061	the mature rAoTanBO	1043:1061	N-terminus of the mature rAoTanBP had six more amino acids than the N-terminus of the mature rAoTanBO.
31492608	3	65	theme	sodium	540:545	arg1	electrophoresis					582:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	sodium dodecyl sulfate polyacrylamide gel electrophoresis	540:596	Purified rAoTanBO showed a smeared band with a molecular mass of approximately 80-100 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis.
31492608	1	66	theme	industrial	250:259	arg1	strain					261:266	an industrial strain	247:266	an industrial strain under the control of an improved glucoamylase gene promoter PglaA142	247:335	A tannase-encoding gene, AotanB, from Aspergillus oryzae RIB40 was overexpressed in A. oryzae AOK11 niaD-deficient mutant derived from an industrial strain under the control of an improved glucoamylase gene promoter PglaA142.
30504678	0	0	theme	Intracellular	63:75	arg1	Trafficking					77:87	Intracellular Trafficking	63:87	Intracellular Trafficking	63:87	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	7	1	theme	Asiatic	1102:1108	arg1	acid					1110:1113	Asiatic acid	1102:1113	Asiatic acid	1102:1113	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	1	2	theme	pentacyclic	158:168	arg1	acid					191:194	The pentacyclic triterpenoid ursolic acid	154:194	The pentacyclic triterpenoid ursolic acid	154:194	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	1	3	theme	adhesion	275:282	arg1	molecule-1					284:293	intercellular adhesion molecule-1	261:293	intercellular adhesion molecule-1 (ICAM-1)	261:302	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	1	3	theme	adhesion	275:282	arg1	ICAM-1					296:301	ICAM-1	296:301	ICAM-1	296:301	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	1	4	theme	Golgi	347:351	arg1	apparatus					353:361	the Golgi apparatus	343:361	the Golgi apparatus	343:361	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	1	5	theme	triterpenoid	170:181	arg1	acid					191:194	The pentacyclic triterpenoid ursolic acid	154:194	The pentacyclic triterpenoid ursolic acid	154:194	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	8	6	theme	ICAM-1	1354:1359	arg1	transport					1341:1349	the intracellular transport	1323:1349	the intracellular transport of ICAM-1 to the cell surface	1323:1379	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	1	7	theme	molecule-1	284:293	arg1	trafficking					246:256	the intracellular trafficking	228:256	the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus	228:361	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	2	8	theme	intracellular	548:560	arg1	trafficking					562:572	intracellular trafficking	548:572	intracellular trafficking	548:572	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	1	9	from	reticulum	325:333	arg1	trafficking					246:256	the intracellular trafficking	228:256	the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus	228:361	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	4	10	theme	maslinic	846:853	arg1	cells					868:872	maslinic acid-treated cells	846:872	maslinic acid-treated cells	846:872	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	3	11	theme	human	588:592	arg1	cells					619:623	human lung adenocarcinoma A549 cells	588:623	human lung adenocarcinoma A549 cells	588:623	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	4	12	theme	H-sensitive	765:775	arg1	glycans					777:783	Endoglycosidase H-sensitive glycans	749:783	Endoglycosidase H-sensitive glycans	749:783	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	5	13	theme	maslinic	915:922	arg1	acid					924:927	maslinic acid	915:927	maslinic acid	915:927	Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein.
30504678	7	14	theme	yeast	1160:1164	arg1	activity					1180:1187	yeast α-glucosidase activity	1160:1187	yeast α-glucosidase activity	1160:1187	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	7	15	theme	maslinic	1136:1143	arg1	acid					1145:1148	maslinic acid	1136:1148	maslinic acid	1136:1148	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	8	16	theme	intracellular	1327:1339	arg1	transport					1341:1349	the intracellular transport	1323:1349	the intracellular transport of ICAM-1 to the cell surface	1323:1379	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	1	17	theme	ursolic	183:189	arg1	acid					191:194	The pentacyclic triterpenoid ursolic acid	154:194	The pentacyclic triterpenoid ursolic acid	154:194	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	0	18	theme	N-Linked	93:100	arg1	Glycosylation					102:114	N-Linked Glycosylation	93:114	N-Linked Glycosylation	93:114	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	4	19	theme	acid-treated	855:866	arg1	cells					868:872	maslinic acid-treated cells	846:872	maslinic acid-treated cells	846:872	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	2	20	theme	pentacyclic	445:455	arg1	triterpenoids					457:469	three pentacyclic triterpenoids	439:469	three pentacyclic triterpenoids closely related to ursolic acid	439:501	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	2	21	theme	triterpenoids	457:469	arg1	activities					425:434	the biological activities	410:434	the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1	410:582	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	3	22	theme	cell	735:738	arg1	surface					740:746	the cell surface	731:746	the cell surface	731:746	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	7	23	theme	Jack	1198:1201	arg1	activity					1222:1229	Jack bean α-mannosidase activity	1198:1229	Jack bean α-mannosidase activity	1198:1229	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	3	24	theme	lung	594:597	arg1	cells					619:623	human lung adenocarcinoma A549 cells	588:623	human lung adenocarcinoma A549 cells	588:623	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	0	25	theme	Asiatic	0:6	arg1	Acid					8:11	Asiatic Acid	0:11	Asiatic Acid	0:11	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	4	26	attach	linked	790:795	arg3	acid-					835:839	corosolic acid-	825:839	corosolic acid-	825:839	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	4	26	attach	linked	790:795	arg3	acid-					818:822	asiatic acid-	810:822	asiatic acid-	810:822	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	4	26	attach	linked	790:795	arg3	cells					868:872	maslinic acid-treated cells	846:872	maslinic acid-treated cells	846:872	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	4	26	attach	linked	790:795	arg1	ICAM-1					800:805	ICAM-1	800:805	ICAM-1	800:805	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	4	26	attach	linked	790:795	arg2	glycans					777:783	Endoglycosidase H-sensitive glycans	749:783	Endoglycosidase H-sensitive glycans	749:783	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	3	27	theme	adenocarcinoma	599:612	arg1	cells					619:623	human lung adenocarcinoma A549 cells	588:623	human lung adenocarcinoma A549 cells	588:623	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	5	28	theme	asiatic	898:904	arg1	acid					906:909	asiatic acid	898:909	asiatic acid	898:909	Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein.
30504678	0	29	theme	Corosolic	14:22	arg1	Acid					24:27	Corosolic Acid	14:27	Corosolic Acid	14:27	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	6	30	theme	asiatic	983:989	arg1	acid					991:994	asiatic acid	983:994	asiatic acid	983:994	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	0	31	theme	Intercellular	119:131	arg1	Molecule-1					142:151	Intercellular Adhesion Molecule-1	119:151	Intercellular Adhesion Molecule-1	119:151	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	5	32	theme	protein	964:970	arg1	protein					964:970	the ICAM-1 protein	953:970	the ICAM-1 protein	953:970	Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein.
30504678	5	32	theme	protein	964:970	arg1	amount					943:948	the amount	939:948	the amount of the ICAM-1 protein	939:970	Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein.
30504678	5	33	theme	ICAM-1	957:962	arg1	protein					964:970	the ICAM-1 protein	953:970	the ICAM-1 protein	953:970	Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein.
30504678	2	34	theme	ICAM-1	577:582	arg1	expression					533:542	interleukin 1α-induced expression	510:542	interleukin 1α-induced expression	510:542	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	2	34	theme	ICAM-1	577:582	arg1	trafficking					562:572	intracellular trafficking	548:572	intracellular trafficking	548:572	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	3	35	theme	maslinic	660:667	arg1	acid					669:672	maslinic acid	660:672	maslinic acid	660:672	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	0	36	gly	Glycosylation	102:114	arg1	Molecule-1					142:151	Intercellular Adhesion Molecule-1	119:151	Intercellular Adhesion Molecule-1	119:151	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	2	37	theme	biological	414:423	arg1	activities					425:434	the biological activities	410:434	the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1	410:582	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	2	38	theme	ursolic	490:496	arg1	acid					498:501	ursolic acid	490:501	ursolic acid	490:501	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	1	39	theme	endoplasmic	313:323	arg1	ER					336:337	ER	336:337	ER	336:337	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	1	39	theme	endoplasmic	313:323	arg1	reticulum					325:333	the endoplasmic reticulum	309:333	the endoplasmic reticulum (ER)	309:338	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	0	40	theme	Molecule-1	142:151	arg1	Trafficking					77:87	Intracellular Trafficking	63:87	Intracellular Trafficking	63:87	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	0	40	theme	Molecule-1	142:151	arg1	Glycosylation					102:114	N-Linked Glycosylation	93:114	N-Linked Glycosylation	93:114	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	7	41	theme	α-glucosidase	1166:1178	arg1	activity					1180:1187	yeast α-glucosidase activity	1160:1187	yeast α-glucosidase activity	1160:1187	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	8	42	theme	cell	1368:1371	arg1	surface					1373:1379	the cell surface	1364:1379	the cell surface	1364:1379	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	6	43	theme	ER	1054:1055	arg1	marker					1057:1062	an ER marker	1051:1062	an ER marker	1051:1062	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	6	43	theme	ER	1054:1055	arg1	calnexin					1041:1048	calnexin	1041:1048	calnexin (an ER marker)	1041:1063	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	5	44	theme	corosolic	882:890	arg1	acid					892:895	corosolic acid	882:895	corosolic acid	882:895	Unlike corosolic acid, asiatic acid and maslinic acid increased the amount of the ICAM-1 protein.
30504678	0	45	theme	Adhesion	133:140	arg1	Molecule-1					142:151	Intercellular Adhesion Molecule-1	119:151	Intercellular Adhesion Molecule-1	119:151	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	8	46	theme	asiatic	1260:1266	arg1	acid					1268:1271	asiatic acid	1260:1271	asiatic acid	1260:1271	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	3	47	theme	asiatic	626:632	arg1	acid					634:637	asiatic acid	626:637	asiatic acid	626:637	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	2	48	theme	1α-induced	522:531	arg1	expression					533:542	interleukin 1α-induced expression	510:542	interleukin 1α-induced expression	510:542	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	0	49	theme	Maslinic	34:41	arg1	Acid					43:46	Maslinic Acid	34:46	Maslinic Acid	34:46	Asiatic Acid, Corosolic Acid, and Maslinic Acid Interfere with Intracellular Trafficking and N-Linked Glycosylation of Intercellular Adhesion Molecule-1.
30504678	7	50	theme	bean	1203:1206	arg1	activity					1222:1229	Jack bean α-mannosidase activity	1198:1229	Jack bean α-mannosidase activity	1198:1229	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	3	51	theme	A549	614:617	arg1	cells					619:623	human lung adenocarcinoma A549 cells	588:623	human lung adenocarcinoma A549 cells	588:623	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	7	52	theme	corosolic	1116:1124	arg1	acid					1126:1129	corosolic acid	1116:1129	corosolic acid	1116:1129	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	2	53	dep	expression	533:542	arg1	the					506:508	the	506:508	the	506:508	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	8	54	theme	maslinic	1294:1301	arg1	acid					1303:1306	maslinic acid	1294:1306	maslinic acid	1294:1306	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	8	55	theme	H-sensitive	1444:1454	arg1	glycans					1456:1462	endoglycosidase H-sensitive glycans	1428:1462	endoglycosidase H-sensitive glycans	1428:1462	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	8	56	theme	ICAM-1	1411:1416	arg1	accumulation					1395:1406	the accumulation	1391:1406	the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans	1391:1462	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	6	57	with	co-localization	1010:1024	arg1	marker					1057:1062	an ER marker	1051:1062	an ER marker	1051:1062	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	6	57	with	co-localization	1010:1024	arg1	marker					1093:1098	a cis-Golgi marker	1081:1098	a cis-Golgi marker	1081:1098	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	6	57	with	co-localization	1010:1024	arg1	calnexin					1041:1048	calnexin	1041:1048	calnexin (an ER marker)	1041:1063	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	6	57	with	co-localization	1010:1024	arg1	GM130					1074:1078	GM130	1074:1078	GM130 (a cis-Golgi marker)	1074:1099	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	3	58	theme	intracellular	694:706	arg1	transport					708:716	the intracellular transport	690:716	the intracellular transport of ICAM-1 to the cell surface	690:746	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	3	59	theme	corosolic	640:648	arg1	acid					650:653	corosolic acid	640:653	corosolic acid	640:653	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	8	60	attach	linked	1418:1423	arg1	glycans					1456:1462	endoglycosidase H-sensitive glycans	1428:1462	endoglycosidase H-sensitive glycans	1428:1462	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	8	60	attach	linked	1418:1423	arg2	accumulation					1395:1406	the accumulation	1391:1406	the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans	1391:1462	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	1	61	theme	intracellular	232:244	arg1	trafficking					246:256	the intracellular trafficking	228:256	the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus	228:361	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	4	62	theme	asiatic	810:816	arg1	acid-					818:822	asiatic acid-	810:822	asiatic acid-	810:822	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	8	63	theme	corosolic	1274:1282	arg1	acid					1284:1287	corosolic acid	1274:1287	corosolic acid	1274:1287	These results indicate that asiatic acid, corosolic acid, and maslinic acid interfere with the intracellular transport of ICAM-1 to the cell surface and cause the accumulation of ICAM-1 linked to endoglycosidase H-sensitive glycans.
30504678	2	64	theme	interleukin	510:520	arg1	expression					533:542	interleukin 1α-induced expression	510:542	interleukin 1α-induced expression	510:542	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	4	65	theme	corosolic	825:833	arg1	acid-					835:839	corosolic acid-	825:839	corosolic acid-	825:839	Endoglycosidase H-sensitive glycans were linked to ICAM-1 in asiatic acid-, corosolic acid-, and maslinic acid-treated cells.
30504678	2	66	theme	present	371:377	arg1	study					379:383	the present study	367:383	the present study	367:383	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	2	67	theme	related	479:485	arg1	triterpenoids					457:469	three pentacyclic triterpenoids	439:469	three pentacyclic triterpenoids closely related to ursolic acid	439:501	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	3	68	theme	ICAM-1	721:726	arg1	transport					708:716	the intracellular transport	690:716	the intracellular transport of ICAM-1 to the cell surface	690:746	In human lung adenocarcinoma A549 cells, asiatic acid, corosolic acid, and maslinic acid interfered with the intracellular transport of ICAM-1 to the cell surface.
30504678	6	69	theme	ICAM-1	1029:1034	arg1	co-localization					1010:1024	the co-localization	1006:1024	the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker)	1006:1099	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	2	70	from	activities	425:434	arg1	expression					533:542	interleukin 1α-induced expression	510:542	interleukin 1α-induced expression	510:542	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	2	70	from	activities	425:434	arg1	trafficking					562:572	intracellular trafficking	548:572	intracellular trafficking	548:572	In the present study, we further investigated the biological activities of three pentacyclic triterpenoids closely related to ursolic acid on the interleukin 1α-induced expression and intracellular trafficking of ICAM-1.
30504678	6	71	theme	cis-Golgi	1083:1091	arg1	marker					1093:1098	a cis-Golgi marker	1081:1098	a cis-Golgi marker	1081:1098	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	6	71	theme	cis-Golgi	1083:1091	arg1	GM130					1074:1078	GM130	1074:1078	GM130 (a cis-Golgi marker)	1074:1099	Moreover, asiatic acid increased the co-localization of ICAM-1 with calnexin (an ER marker), but not GM130 (a cis-Golgi marker).
30504678	7	72	theme	α-mannosidase	1208:1220	arg1	activity					1222:1229	Jack bean α-mannosidase activity	1198:1229	Jack bean α-mannosidase activity	1198:1229	Asiatic acid, corosolic acid, and maslinic acid inhibited yeast α-glucosidase activity, but not Jack bean α-mannosidase activity.
30504678	1	73	theme	intercellular	261:273	arg1	molecule-1					284:293	intercellular adhesion molecule-1	261:293	intercellular adhesion molecule-1 (ICAM-1)	261:302	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30504678	1	73	theme	intercellular	261:273	arg1	ICAM-1					296:301	ICAM-1	296:301	ICAM-1	296:301	The pentacyclic triterpenoid ursolic acid was previously shown to inhibit the intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1) from the endoplasmic reticulum (ER) to the Golgi apparatus.
30318473	7	0	theme	glycan	971:976	arg1	addition					947:954	addition	947:954	addition of an N-linked glycan to the furin-recognition site	947:1006	One of these mutations introduces a motif for addition of an N-linked glycan to the furin-recognition site.
30318473	4	1	theme	LPL	408:410	arg1	use					401:403	use	401:403	use of LPL as a protein therapeutic	401:435	However, use of LPL as a protein therapeutic is limited because it is an unstable enzyme that is difficult to produce in large quantities.
30318473	9	2	theme	in	1179:1180	arg1	function					1187:1194	in vivo function	1179:1194	in vivo function	1179:1194	We show that our modifications do not adversely alter LPL's enzymatic activity, stability, or in vivo function.
30318473	9	3	theme	enzymatic	1145:1153	arg1	activity					1155:1162	LPL's enzymatic activity	1139:1162	LPL's enzymatic activity	1139:1162	We show that our modifications do not adversely alter LPL's enzymatic activity, stability, or in vivo function.
30318473	3	4	theme	therapeutic	379:389	arg1	LPL					362:364	recombinant LPL	350:364	recombinant LPL	350:364	One potential treatment is to administer recombinant LPL as a protein therapeutic.
30318473	3	4	theme	therapeutic	379:389	arg1	protein					371:377	a protein therapeutic	369:389	a protein therapeutic	369:389	One potential treatment is to administer recombinant LPL as a protein therapeutic.
30318473	6	5	theme	novel	806:810	arg1	mutations					812:820	novel mutations	806:820	novel mutations	806:820	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	10	6	theme	useful	1253:1258	arg1	LPL					1244:1246	furin-resistant LPL	1228:1246	furin-resistant LPL	1228:1246	Together, these data show that furin-resistant LPL is a useful reagent for both biochemical and biomedical studies.
30318473	10	6	theme	useful	1253:1258	arg1	reagent					1260:1266	a useful reagent	1251:1266	a useful reagent for both biochemical and biomedical studies	1251:1310	Together, these data show that furin-resistant LPL is a useful reagent for both biochemical and biomedical studies.
30318473	4	7	theme	unstable	465:472	arg1	it					456:457	it	456:457	it	456:457	However, use of LPL as a protein therapeutic is limited because it is an unstable enzyme that is difficult to produce in large quantities.
30318473	4	7	theme	unstable	465:472	arg1	enzyme					474:479	an unstable enzyme	462:479	an unstable enzyme that is difficult to produce in large quantities	462:528	However, use of LPL as a protein therapeutic is limited because it is an unstable enzyme that is difficult to produce in large quantities.
30318473	4	7	theme	unstable	465:472	arg1	difficult					489:497	difficult	489:497	difficult	489:497	However, use of LPL as a protein therapeutic is limited because it is an unstable enzyme that is difficult to produce in large quantities.
30318473	2	8	theme	acute	289:293	arg1	pancreatitis					295:306	acute pancreatitis	289:306	acute pancreatitis	289:306	Individuals lacking LPL suffer from severe hypertriglyceridemia, a risk factor for acute pancreatitis.
30318473	5	9	theme	large-scale	631:641	arg1	efforts					658:664	large-scale drug discovery efforts	631:664	large-scale drug discovery efforts	631:664	Furthermore, these considerations also limit structural and biochemical studies that are needed for large-scale drug discovery efforts.
30318473	6	10	theme	LPL	709:711	arg1	yield					691:695	the yield	687:695	the yield of purified LPL	687:711	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	8	11	used	used	1079:1082	arg2	LPL					1025:1027	Furin-resistant LPL	1009:1027	Furin-resistant LPL	1009:1027	Furin-resistant LPL has previously been reported, but is not commonly used.
30318473	6	12	theme	proteolytic	870:880	arg1	cleavage					882:889	proteolytic cleavage	870:889	proteolytic cleavage by furin	870:898	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	5	13	theme	drug	643:646	arg1	efforts					658:664	large-scale drug discovery efforts	631:664	large-scale drug discovery efforts	631:664	Furthermore, these considerations also limit structural and biochemical studies that are needed for large-scale drug discovery efforts.
30318473	5	14	theme	structural	576:585	arg1	studies					603:609	structural and biochemical studies	576:609	structural and biochemical studies that are needed for large-scale drug discovery efforts	576:664	Furthermore, these considerations also limit structural and biochemical studies that are needed for large-scale drug discovery efforts.
30318473	6	15	theme	purified	700:707	arg1	LPL					709:711	purified LPL	700:711	purified LPL	700:711	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	1	16	theme	circulating	180:190	arg1	lipoproteins					192:203	circulating lipoproteins	180:203	circulating lipoproteins	180:203	LPL is a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins.
30318473	7	17	link	N-linked	962:969	arg1	glycan					971:976	an N-linked glycan	959:976	an N-linked glycan	959:976	One of these mutations introduces a motif for addition of an N-linked glycan to the furin-recognition site.
30318473	5	18	theme	discovery	648:656	arg1	efforts					658:664	large-scale drug discovery efforts	631:664	large-scale drug discovery efforts	631:664	Furthermore, these considerations also limit structural and biochemical studies that are needed for large-scale drug discovery efforts.
30318473	7	19	theme	mutations	914:922	arg1	One					901:903	One	901:903	One	901:903	One of these mutations introduces a motif for addition of an N-linked glycan to the furin-recognition site.
30318473	7	19	theme	mutations	914:922	arg1	mutations					914:922	these mutations	908:922	these mutations	908:922	One of these mutations introduces a motif for addition of an N-linked glycan to the furin-recognition site.
30318473	10	20	theme	biomedical	1293:1302	arg1	studies					1304:1310	both biochemical and biomedical studies	1272:1310	both biochemical and biomedical studies	1272:1310	Together, these data show that furin-resistant LPL is a useful reagent for both biochemical and biomedical studies.
30318473	10	21	theme	biochemical	1277:1287	arg1	studies					1304:1310	both biochemical and biomedical studies	1272:1310	both biochemical and biomedical studies	1272:1310	Together, these data show that furin-resistant LPL is a useful reagent for both biochemical and biomedical studies.
30318473	0	22	theme	furin-resistant	22:36	arg1	variants					42:49	novel furin-resistant LPL variants	16:49	novel furin-resistant LPL variants	16:49	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30318473	8	23	theme	Furin-resistant	1009:1023	arg1	LPL					1025:1027	Furin-resistant LPL	1009:1027	Furin-resistant LPL	1009:1027	Furin-resistant LPL has previously been reported, but is not commonly used.
30318473	5	24	theme	biochemical	591:601	arg1	studies					603:609	structural and biochemical studies	576:609	structural and biochemical studies that are needed for large-scale drug discovery efforts	576:664	Furthermore, these considerations also limit structural and biochemical studies that are needed for large-scale drug discovery efforts.
30318473	0	25	theme	novel	16:20	arg1	variants					42:49	novel furin-resistant LPL variants	16:49	novel furin-resistant LPL variants	16:49	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30318473	7	26	theme	furin-recognition	985:1001	arg1	site					1003:1006	the furin-recognition site	981:1006	the furin-recognition site	981:1006	One of these mutations introduces a motif for addition of an N-linked glycan to the furin-recognition site.
30318473	0	27	theme	variants	42:49	arg1	Coexpression					0:11	Coexpression	0:11	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1	0:81	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30318473	0	28	theme	LPL	38:40	arg1	variants					42:49	novel furin-resistant LPL variants	16:49	novel furin-resistant LPL variants	16:49	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30318473	2	29	theme	severe	242:247	arg1	hypertriglyceridemia					249:268	severe hypertriglyceridemia	242:268	severe hypertriglyceridemia	242:268	Individuals lacking LPL suffer from severe hypertriglyceridemia, a risk factor for acute pancreatitis.
30318473	2	29	theme	severe	242:247	arg1	factor					278:283	a risk factor	271:283	a risk factor for acute pancreatitis	271:306	Individuals lacking LPL suffer from severe hypertriglyceridemia, a risk factor for acute pancreatitis.
30318473	0	30	theme	lipase	56:61	arg1	factor					74:79	lipase maturation factor 1	56:81	lipase maturation factor 1	56:81	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30318473	4	31	theme	large	513:517	arg1	quantities					519:528	large quantities	513:528	large quantities	513:528	However, use of LPL as a protein therapeutic is limited because it is an unstable enzyme that is difficult to produce in large quantities.
30318473	4	32	theme	therapeutic	425:435	arg1	protein					417:423	a protein therapeutic	415:435	a protein therapeutic	415:435	However, use of LPL as a protein therapeutic is limited because it is an unstable enzyme that is difficult to produce in large quantities.
30318473	6	33	theme	maturation	762:771	arg1	LMF1					781:784	LMF1	781:784	LMF1	781:784	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	6	33	theme	maturation	762:771	arg1	factor					773:778	its maturation factor	758:778	its maturation factor	758:778	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	6	34	dep	enhanced	733:740	arg1	coexpressing					745:756	coexpressing	745:756	coexpressing its maturation factor, LMF1,	745:785	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	6	34	dep	enhanced	733:740	arg1	introducing					794:804	introducing	794:804	introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin	794:898	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	0	35	with	Coexpression	0:11	arg1	factor					74:79	lipase maturation factor 1	56:81	lipase maturation factor 1	56:81	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30318473	3	36	theme	potential	313:321	arg1	treatment					323:331	One potential treatment	309:331	One potential treatment	309:331	One potential treatment is to administer recombinant LPL as a protein therapeutic.
30318473	6	37	theme	LPL	831:833	arg1	sequence					835:842	the LPL sequence	827:842	the LPL sequence to render it resistant to proteolytic cleavage by furin	827:898	We demonstrate that the yield of purified LPL can be dramatically enhanced by coexpressing its maturation factor, LMF1, and by introducing novel mutations into the LPL sequence to render it resistant to proteolytic cleavage by furin.
30318473	2	38	theme	risk	273:276	arg1	hypertriglyceridemia					249:268	severe hypertriglyceridemia	242:268	severe hypertriglyceridemia	242:268	Individuals lacking LPL suffer from severe hypertriglyceridemia, a risk factor for acute pancreatitis.
30318473	2	38	theme	risk	273:276	arg1	factor					278:283	a risk factor	271:283	a risk factor for acute pancreatitis	271:306	Individuals lacking LPL suffer from severe hypertriglyceridemia, a risk factor for acute pancreatitis.
30318473	3	39	theme	recombinant	350:360	arg1	LPL					362:364	recombinant LPL	350:364	recombinant LPL	350:364	One potential treatment is to administer recombinant LPL as a protein therapeutic.
30318473	3	39	theme	recombinant	350:360	arg1	protein					371:377	a protein therapeutic	369:389	a protein therapeutic	369:389	One potential treatment is to administer recombinant LPL as a protein therapeutic.
30318473	9	40	dep	in	1179:1180	arg1	vivo					1182:1185	vivo	1182:1185	vivo	1182:1185	We show that our modifications do not adversely alter LPL's enzymatic activity, stability, or in vivo function.
30318473	1	41	from	lipoproteins	192:203	arg1	triglycerides					161:173	triglycerides	161:173	triglycerides from circulating lipoproteins	161:203	LPL is a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins.
30318473	1	42	theme	secreted	129:136	arg1	enzyme					138:143	a secreted enzyme	127:143	a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins	127:203	LPL is a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins.
30318473	1	42	theme	secreted	129:136	arg1	LPL					120:122	LPL	120:122	LPL	120:122	LPL is a secreted enzyme that hydrolyzes triglycerides from circulating lipoproteins.
30318473	0	43	theme	maturation	63:72	arg1	factor					74:79	lipase maturation factor 1	56:81	lipase maturation factor 1	56:81	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30318473	7	44	theme	N-linked	962:969	arg1	glycan					971:976	an N-linked glycan	959:976	an N-linked glycan	959:976	One of these mutations introduces a motif for addition of an N-linked glycan to the furin-recognition site.
30318473	10	45	theme	furin-resistant	1228:1242	arg1	LPL					1244:1246	furin-resistant LPL	1228:1246	furin-resistant LPL	1228:1246	Together, these data show that furin-resistant LPL is a useful reagent for both biochemical and biomedical studies.
30318473	10	45	theme	furin-resistant	1228:1242	arg1	reagent					1260:1266	a useful reagent	1251:1266	a useful reagent for both biochemical and biomedical studies	1251:1310	Together, these data show that furin-resistant LPL is a useful reagent for both biochemical and biomedical studies.
30318473	0	46	theme	LPL	92:94	arg1	secretion					96:104	LPL secretion	92:104	LPL secretion	92:104	Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity.
30201803	1	0	theme	side	279:282	arg1	chains					284:289	N-linked oligosaccharide side chains	254:289	N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	254:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	3	1	theme	urine	779:783	arg1	screening					785:793	urine screening	779:793	urine screening of glycoproteinoses and other LSDs	779:828	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	6	2	from	controls	1168:1175	arg1	samples					1139:1145	Urine samples	1133:1145	Urine samples from >100 unaffected controls and 37 patients with various LSDs	1133:1209	Urine samples from >100 unaffected controls and 37 patients with various LSDs were studied.
30201803	9	3	theme	future	1799:1804	arg1	monitoring					1816:1825	future treatment monitoring	1799:1825	future treatment monitoring	1799:1825	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	7	4	with	patients	1360:1367	arg1	aspartylglucosaminuria					1397:1418	aspartylglucosaminuria	1397:1418	aspartylglucosaminuria	1397:1418	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	sialidosis					1514:1523	sialidosis	1514:1523	sialidosis	1514:1523	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	α-fucosidosis					1421:1433	α-fucosidosis	1421:1433	α-fucosidosis	1421:1433	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	deficiency					1484:1493	β-galactosidase deficiency	1468:1493	β-galactosidase deficiency	1468:1493	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	LSDs					1391:1394	1 of 8 different LSDs	1374:1394	1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis	1374:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	galactosialidosis					1530:1546	galactosialidosis	1530:1546	galactosialidosis	1530:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	α-mannosidosis					1436:1449	α-mannosidosis	1436:1449	α-mannosidosis	1436:1449	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	β-mannosidosis					1452:1465	β-mannosidosis	1452:1465	β-mannosidosis	1452:1465	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	4	with	patients	1360:1367	arg1	disease					1505:1511	Sandhoff disease	1496:1511	Sandhoff disease	1496:1511	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	1	5	theme	storage	191:197	arg1	diseases					199:206	lysosomal storage diseases	181:206	lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	181:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	5	theme	storage	191:197	arg1	LSDs					209:212	LSDs	209:212	LSDs	209:212	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	6	6	with	patients	1184:1191	arg1	LSDs					1206:1209	various LSDs	1198:1209	various LSDs	1198:1209	Urine samples from >100 unaffected controls and 37 patients with various LSDs were studied.
30201803	3	7	theme	sensitive	605:613	arg1	assay					639:643	an analytically sensitive and relatively specific assay	589:643	an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis	589:751	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	7	8	theme	Sandhoff	1496:1503	arg1	LSDs					1391:1394	1 of 8 different LSDs	1374:1394	1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis	1374:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	8	theme	Sandhoff	1496:1503	arg1	disease					1505:1511	Sandhoff disease	1496:1511	Sandhoff disease	1496:1511	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	1	9	theme	thin	408:411	arg1	TLC					435:437	TLC	435:437	TLC	435:437	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	9	theme	thin	408:411	arg1	chromatography					419:432	thin layer chromatography	408:432	thin layer chromatography (TLC)	408:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	4	10	theme	extraction	971:980	arg1	cartridge					982:990	a solid-phase extraction cartridge	957:990	a solid-phase extraction cartridge	957:990	METHODS Urine volumes equivalent to 30 μg of creatinine were derivatized with butyl-4-aminobenzoate and then purified through a solid-phase extraction cartridge.
30201803	3	11	theme	LSDs	825:828	arg1	screening					785:793	urine screening	779:793	urine screening of glycoproteinoses and other LSDs	779:828	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	5	12	theme	FOS	1128:1130	arg1	separation					1102:1111	separation	1102:1111	separation of derivatized FOS	1102:1130	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	5	13	theme	7-min	995:999	arg1	analysis					1012:1019	A 7-min UPLC-MS/MS analysis	993:1019	A 7-min UPLC-MS/MS analysis	993:1019	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	8	14	theme	stem	1585:1588	arg1	transplant					1595:1604	hematopoietic stem cell transplant	1571:1604	hematopoietic stem cell transplant	1571:1604	Patients treated with hematopoietic stem cell transplant show decreased FOS responses compared with untreated patients.
30201803	9	15	dep	CONCLUSIONS	1669:1679	arg1	offers					1703:1708	offers	1703:1708	offers	1703:1708	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	3	16	theme	chromatography-tandem	675:695	arg1	UPLC-MS/MS					716:725	UPLC-MS/MS	716:725	UPLC-MS/MS	716:725	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	3	16	theme	chromatography-tandem	675:695	arg1	spectrometry					702:713	ultraperformance liquid chromatography-tandem mass spectrometry	651:713	ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)	651:726	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	0	17	theme	Storage	67:73	arg1	Diseases					75:82	Lysosomal Storage Diseases	57:82	Lysosomal Storage Diseases	57:82	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	3	18	theme	ultraperformance	651:666	arg1	UPLC-MS/MS					716:725	UPLC-MS/MS	716:725	UPLC-MS/MS	716:725	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	3	18	theme	ultraperformance	651:666	arg1	spectrometry					702:713	ultraperformance liquid chromatography-tandem mass spectrometry	651:713	ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)	651:726	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	8	19	theme	decreased	1611:1619	arg1	responses					1625:1633	decreased FOS responses	1611:1633	decreased FOS responses	1611:1633	Patients treated with hematopoietic stem cell transplant show decreased FOS responses compared with untreated patients.
30201803	1	20	theme	free	366:369	arg1	FOSs					389:392	FOSs	389:392	FOSs	389:392	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	20	theme	free	366:369	arg1	oligosaccharides					371:386	the accumulated free oligosaccharides	350:386	the accumulated free oligosaccharides (FOSs) in urine	350:402	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	5	21	theme	quadrupole	1047:1056	arg1	spectrometer					1063:1074	a triple quadrupole mass spectrometer	1038:1074	a triple quadrupole mass spectrometer	1038:1074	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	4	22	theme	Urine	839:843	arg1	volumes					845:851	METHODS Urine volumes	831:851	METHODS Urine volumes equivalent to 30 μg of creatinine	831:885	METHODS Urine volumes equivalent to 30 μg of creatinine were derivatized with butyl-4-aminobenzoate and then purified through a solid-phase extraction cartridge.
30201803	0	23	theme	Treatment	109:117	arg1	Monitoring					119:128	Potential Treatment Monitoring	99:128	Potential Treatment Monitoring	99:128	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	0	24	theme	Oligosaccharides	36:51	arg1	Analysis					11:18	UPLC-MS/MS Analysis	0:18	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.	0:129	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	6	25	theme	unaffected	1157:1166	arg1	controls					1168:1175	>100 unaffected controls	1152:1175	>100 unaffected controls	1152:1175	Urine samples from >100 unaffected controls and 37 patients with various LSDs were studied.
30201803	2	26	theme	TLC	457:459	arg1	method					461:466	The traditional TLC method	441:466	The traditional TLC method	441:466	The traditional TLC method suffers from limited analytical sensitivity and specificity and lacks quantification capability.
30201803	0	27	theme	UPLC-MS/MS	0:9	arg1	Analysis					11:18	UPLC-MS/MS Analysis	0:18	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.	0:129	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	1	28	theme	glycoproteins	294:306	arg1	chains					284:289	N-linked oligosaccharide side chains	254:289	N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	254:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	0	29	dep	Analysis	11:18	arg1	Diagnosis					85:93	Diagnosis	85:93	Diagnosis	85:93	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	0	29	dep	Analysis	11:18	arg1	Monitoring					119:128	Potential Treatment Monitoring	99:128	Potential Treatment Monitoring	99:128	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	6	30	theme	Urine	1133:1137	arg1	samples					1139:1145	Urine samples	1133:1145	Urine samples from >100 unaffected controls and 37 patients with various LSDs	1133:1209	Urine samples from >100 unaffected controls and 37 patients with various LSDs were studied.
30201803	2	31	theme	limited	481:487	arg1	sensitivity					500:510	limited analytical sensitivity	481:510	limited analytical sensitivity	481:510	The traditional TLC method suffers from limited analytical sensitivity and specificity and lacks quantification capability.
30201803	0	32	theme	Free	31:34	arg1	Oligosaccharides					36:51	Urinary Free Oligosaccharides	23:51	Urinary Free Oligosaccharides	23:51	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	1	33	from	oligosaccharides	371:386	arg1	urine					398:402	urine	398:402	urine	398:402	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	6	34	with	controls	1168:1175	arg1	LSDs					1206:1209	various LSDs	1198:1209	various LSDs	1198:1209	Urine samples from >100 unaffected controls and 37 patients with various LSDs were studied.
30201803	7	35	theme	RESULTS	1225:1231	arg1	quantification					1242:1255	RESULTS Relative quantification	1225:1255	RESULTS Relative quantification	1225:1255	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	5	36	theme	derivatized	1116:1126	arg1	FOS					1128:1130	derivatized FOS	1116:1130	derivatized FOS	1116:1130	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	3	37	theme	FOS	740:742	arg1	analysis					744:751	urinary FOS analysis	732:751	urinary FOS analysis	732:751	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	4	38	theme	equivalent	853:862	arg1	volumes					845:851	METHODS Urine volumes	831:851	METHODS Urine volumes equivalent to 30 μg of creatinine	831:885	METHODS Urine volumes equivalent to 30 μg of creatinine were derivatized with butyl-4-aminobenzoate and then purified through a solid-phase extraction cartridge.
30201803	1	39	theme	impaired	230:237	arg1	degradation					239:249	impaired degradation	230:249	impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	230:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	9	40	theme	other	1764:1768	arg1	LSDs					1770:1773	other LSDs	1764:1773	other LSDs	1764:1773	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	7	41	theme	patients	1360:1367	arg1	identification					1342:1355	the identification	1338:1355	the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis	1338:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	aspartylglucosaminuria					1397:1418	aspartylglucosaminuria	1397:1418	aspartylglucosaminuria	1397:1418	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	sialidosis					1514:1523	sialidosis	1514:1523	sialidosis	1514:1523	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	α-fucosidosis					1421:1433	α-fucosidosis	1421:1433	α-fucosidosis	1421:1433	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	deficiency					1484:1493	β-galactosidase deficiency	1468:1493	β-galactosidase deficiency	1468:1493	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	LSDs					1391:1394	1 of 8 different LSDs	1374:1394	1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis	1374:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	galactosialidosis					1530:1546	galactosialidosis	1530:1546	galactosialidosis	1530:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	α-mannosidosis					1436:1449	α-mannosidosis	1436:1449	α-mannosidosis	1436:1449	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	β-mannosidosis					1452:1465	β-mannosidosis	1452:1465	β-mannosidosis	1452:1465	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	42	dep	LSDs	1391:1394	arg1	disease					1505:1511	Sandhoff disease	1496:1511	Sandhoff disease	1496:1511	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	6	43	from	patients	1184:1191	arg1	samples					1139:1145	Urine samples	1133:1145	Urine samples from >100 unaffected controls and 37 patients with various LSDs	1133:1209	Urine samples from >100 unaffected controls and 37 patients with various LSDs were studied.
30201803	1	44	theme	oligosaccharide	263:277	arg1	chains					284:289	N-linked oligosaccharide side chains	254:289	N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	254:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	9	45	theme	potential	1781:1789	arg1	use					1791:1793	potential use	1781:1793	potential use for future treatment monitoring	1781:1825	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	1	46	theme	chains	284:289	arg1	degradation					239:249	impaired degradation	230:249	impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	230:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	47	theme	lysosomal	181:189	arg1	diseases					199:206	lysosomal storage diseases	181:206	lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	181:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	47	theme	lysosomal	181:189	arg1	LSDs					209:212	LSDs	209:212	LSDs	209:212	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	9	48	theme	treatment	1806:1814	arg1	monitoring					1816:1825	future treatment monitoring	1799:1825	future treatment monitoring	1799:1825	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	1	49	link	N-linked	254:261	arg1	chains					284:289	N-linked oligosaccharide side chains	254:289	N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	254:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	50	theme	diseases	199:206	arg1	glycoproteinoses					146:161	The glycoproteinoses	142:161	The glycoproteinoses	142:161	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	50	theme	diseases	199:206	arg1	subgroup					169:176	a subgroup	167:176	a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	167:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	3	51	theme	other	819:823	arg1	LSDs					825:828	other LSDs	819:828	other LSDs	819:828	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	9	52	theme	glycoproteinoses	1743:1758	arg1	screening					1730:1738	screening	1730:1738	screening of glycoproteinoses and other LSDs	1730:1773	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	3	53	theme	glycoproteinoses	798:813	arg1	screening					785:793	urine screening	779:793	urine screening of glycoproteinoses and other LSDs	779:828	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	3	54	theme	specific	630:637	arg1	assay					639:643	an analytically sensitive and relatively specific assay	589:643	an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis	589:751	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	8	55	theme	hematopoietic	1571:1583	arg1	transplant					1595:1604	hematopoietic stem cell transplant	1571:1604	hematopoietic stem cell transplant	1571:1604	Patients treated with hematopoietic stem cell transplant show decreased FOS responses compared with untreated patients.
30201803	1	56	theme	layer	413:417	arg1	TLC					435:437	TLC	435:437	TLC	435:437	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	56	theme	layer	413:417	arg1	chromatography					419:432	thin layer chromatography	408:432	thin layer chromatography (TLC)	408:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	57	gly	glycoproteins	294:306	arg1	glycoproteins					294:306	glycoproteins	294:306	glycoproteins	294:306	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	4	58	theme	solid-phase	959:969	arg1	cartridge					982:990	a solid-phase extraction cartridge	957:990	a solid-phase extraction cartridge	957:990	METHODS Urine volumes equivalent to 30 μg of creatinine were derivatized with butyl-4-aminobenzoate and then purified through a solid-phase extraction cartridge.
30201803	8	59	theme	cell	1590:1593	arg1	transplant					1595:1604	hematopoietic stem cell transplant	1571:1604	hematopoietic stem cell transplant	1571:1604	Patients treated with hematopoietic stem cell transplant show decreased FOS responses compared with untreated patients.
30201803	7	60	theme	β-galactosidase	1468:1482	arg1	LSDs					1391:1394	1 of 8 different LSDs	1374:1394	1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis	1374:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	60	theme	β-galactosidase	1468:1482	arg1	deficiency					1484:1493	β-galactosidase deficiency	1468:1493	β-galactosidase deficiency	1468:1493	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	3	61	theme	liquid	668:673	arg1	UPLC-MS/MS					716:725	UPLC-MS/MS	716:725	UPLC-MS/MS	716:725	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	3	61	theme	liquid	668:673	arg1	spectrometry					702:713	ultraperformance liquid chromatography-tandem mass spectrometry	651:713	ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)	651:726	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	5	62	theme	UPLC-MS/MS	1001:1010	arg1	analysis					1012:1019	A 7-min UPLC-MS/MS analysis	993:1019	A 7-min UPLC-MS/MS analysis	993:1019	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	8	63	theme	FOS	1621:1623	arg1	responses					1625:1633	decreased FOS responses	1611:1633	decreased FOS responses	1611:1633	Patients treated with hematopoietic stem cell transplant show decreased FOS responses compared with untreated patients.
30201803	1	64	theme	accumulated	354:364	arg1	FOSs					389:392	FOSs	389:392	FOSs	389:392	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	64	theme	accumulated	354:364	arg1	oligosaccharides					371:386	the accumulated free oligosaccharides	350:386	the accumulated free oligosaccharides (FOSs) in urine	350:402	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	2	65	theme	analytical	489:498	arg1	sensitivity					500:510	limited analytical sensitivity	481:510	limited analytical sensitivity	481:510	The traditional TLC method suffers from limited analytical sensitivity and specificity and lacks quantification capability.
30201803	0	66	theme	Potential	99:107	arg1	Monitoring					119:128	Potential Treatment Monitoring	99:128	Potential Treatment Monitoring	99:128	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	5	67	theme	triple	1040:1045	arg1	spectrometer					1063:1074	a triple quadrupole mass spectrometer	1038:1074	a triple quadrupole mass spectrometer	1038:1074	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	2	68	theme	quantification	538:551	arg1	capability					553:562	quantification capability	538:562	quantification capability	538:562	The traditional TLC method suffers from limited analytical sensitivity and specificity and lacks quantification capability.
30201803	8	69	theme	untreated	1649:1657	arg1	patients					1659:1666	untreated patients	1649:1666	untreated patients	1649:1666	Patients treated with hematopoietic stem cell transplant show decreased FOS responses compared with untreated patients.
30201803	6	70	theme	various	1198:1204	arg1	LSDs					1206:1209	various LSDs	1198:1209	various LSDs	1198:1209	Urine samples from >100 unaffected controls and 37 patients with various LSDs were studied.
30201803	7	71	theme	selected	1276:1283	arg1	FOSs					1285:1288	7 selected FOSs	1274:1288	7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis	1274:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	5	72	theme	mass	1058:1061	arg1	spectrometer					1063:1074	a triple quadrupole mass spectrometer	1038:1074	a triple quadrupole mass spectrometer	1038:1074	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	1	73	dep	BACKGROUND	131:140	arg1	glycoproteinoses					146:161	The glycoproteinoses	142:161	The glycoproteinoses	142:161	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	1	73	dep	BACKGROUND	131:140	arg1	subgroup					169:176	a subgroup	167:176	a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	167:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
30201803	2	74	theme	traditional	445:455	arg1	method					461:466	The traditional TLC method	441:466	The traditional TLC method	441:466	The traditional TLC method suffers from limited analytical sensitivity and specificity and lacks quantification capability.
30201803	0	75	theme	Urinary	23:29	arg1	Oligosaccharides					36:51	Urinary Free Oligosaccharides	23:51	Urinary Free Oligosaccharides	23:51	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	9	76	theme	LSDs	1770:1773	arg1	screening					1730:1738	screening	1730:1738	screening of glycoproteinoses and other LSDs	1730:1773	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	9	77	theme	valuable	1712:1719	arg1	tool					1721:1724	a valuable tool	1710:1724	a valuable tool for screening of glycoproteinoses and other LSDs	1710:1773	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	7	78	theme	different	1381:1389	arg1	aspartylglucosaminuria					1397:1418	aspartylglucosaminuria	1397:1418	aspartylglucosaminuria	1397:1418	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	sialidosis					1514:1523	sialidosis	1514:1523	sialidosis	1514:1523	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	α-fucosidosis					1421:1433	α-fucosidosis	1421:1433	α-fucosidosis	1421:1433	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	deficiency					1484:1493	β-galactosidase deficiency	1468:1493	β-galactosidase deficiency	1468:1493	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	LSDs					1391:1394	1 of 8 different LSDs	1374:1394	1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis	1374:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	galactosialidosis					1530:1546	galactosialidosis	1530:1546	galactosialidosis	1530:1546	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	α-mannosidosis					1436:1449	α-mannosidosis	1436:1449	α-mannosidosis	1436:1449	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	β-mannosidosis					1452:1465	β-mannosidosis	1452:1465	β-mannosidosis	1452:1465	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	7	78	theme	different	1381:1389	arg1	disease					1505:1511	Sandhoff disease	1496:1511	Sandhoff disease	1496:1511	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	9	79	theme	UPLC-MS/MS	1686:1695	arg1	assay					1697:1701	This UPLC-MS/MS assay	1681:1701	This UPLC-MS/MS assay	1681:1701	CONCLUSIONS This UPLC-MS/MS assay offers a valuable tool for screening of glycoproteinoses and other LSDs, with potential use for future treatment monitoring.
30201803	7	80	theme	Relative	1233:1240	arg1	quantification					1242:1255	RESULTS Relative quantification	1225:1255	RESULTS Relative quantification	1225:1255	RESULTS Relative quantification was conducted on 7 selected FOSs using a single internal standard, which allowed the identification of patients with 1 of 8 different LSDs: aspartylglucosaminuria, α-fucosidosis, α-mannosidosis, β-mannosidosis, β-galactosidase deficiency, Sandhoff disease, sialidosis, and galactosialidosis.
30201803	3	81	theme	mass	697:700	arg1	UPLC-MS/MS					716:725	UPLC-MS/MS	716:725	UPLC-MS/MS	716:725	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	3	81	theme	mass	697:700	arg1	spectrometry					702:713	ultraperformance liquid chromatography-tandem mass spectrometry	651:713	ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)	651:726	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	0	82	theme	Lysosomal	57:65	arg1	Diseases					75:82	Lysosomal Storage Diseases	57:82	Lysosomal Storage Diseases	57:82	UPLC-MS/MS Analysis of Urinary Free Oligosaccharides for Lysosomal Storage Diseases: Diagnosis and Potential Treatment Monitoring.
30201803	3	83	theme	urinary	732:738	arg1	analysis					744:751	urinary FOS analysis	732:751	urinary FOS analysis	732:751	Therefore, we developed an analytically sensitive and relatively specific assay using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for urinary FOS analysis and validated its use for urine screening of glycoproteinoses and other LSDs.
30201803	4	84	theme	creatinine	876:885	arg1	μg					870:871	30 μg	867:871	30 μg of creatinine	867:885	METHODS Urine volumes equivalent to 30 μg of creatinine were derivatized with butyl-4-aminobenzoate and then purified through a solid-phase extraction cartridge.
30201803	4	85	theme	METHODS	831:837	arg1	volumes					845:851	METHODS Urine volumes	831:851	METHODS Urine volumes equivalent to 30 μg of creatinine	831:885	METHODS Urine volumes equivalent to 30 μg of creatinine were derivatized with butyl-4-aminobenzoate and then purified through a solid-phase extraction cartridge.
30201803	5	86	theme	amide	1085:1089	arg1	column					1091:1096	an amide column	1082:1096	an amide column for separation of derivatized FOS	1082:1130	A 7-min UPLC-MS/MS analysis was performed on a triple quadrupole mass spectrometer using an amide column for separation of derivatized FOS.
30201803	1	87	theme	N-linked	254:261	arg1	chains					284:289	N-linked oligosaccharide side chains	254:289	N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC)	254:438	BACKGROUND The glycoproteinoses are a subgroup of lysosomal storage diseases (LSDs) resulting from impaired degradation of N-linked oligosaccharide side chains of glycoproteins, which are commonly screened by detecting the accumulated free oligosaccharides (FOSs) in urine via thin layer chromatography (TLC).
29508463	8	0	theme	important	1521:1529	arg1	limitations					1531:1541	identified important limitations	1510:1541	identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes	1510:1610	This study has identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes.
29508463	6	1	theme	vicinal	1318:1324	arg1	amine					1338:1342	a vicinal, protonated amine	1316:1342	amine	1338:1342	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	2	2	theme	"	393:393	arg1	intermediate					395:406	a 1,2-anhydrosugar "epoxide" intermediate	366:406	a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates	366:457	They are proposed to act through a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates.
29508463	7	3	theme	unfavourable	1431:1442	arg1	interaction					1444:1454	an unfavourable interaction	1428:1454	an unfavourable interaction with a conserved active site tyrosine	1428:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	1	4	link	N-linked	250:257	arg1	glycans					259:265	mammalian N-linked glycans	240:265	mammalian N-linked glycans	240:265	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	2	5	theme	epoxide	386:392	arg1	intermediate					395:406	a 1,2-anhydrosugar "epoxide" intermediate	366:406	a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates	366:457	They are proposed to act through a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates.
29508463	6	6	from	reduction	1241:1249	arg1	basicity					1254:1261	basicity	1254:1261	basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2	1254:1348	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	6	7	theme	iminosugar	1052:1061	arg1	inhibitors					1063:1072	other iminosugar inhibitors	1046:1072	other iminosugar inhibitors	1046:1072	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	3	8	theme	glycosidic	577:586	arg1	bond					588:591	the fissile glycosidic bond	565:591	the fissile glycosidic bond	565:591	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	6	9	theme	other	1046:1050	arg1	inhibitors					1063:1072	other iminosugar inhibitors	1046:1072	other iminosugar inhibitors	1046:1072	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	8	10	theme	inhibitor	1578:1586	arg1	design					1588:1593	mechanism-inspired inhibitor design	1559:1593	mechanism-inspired inhibitor design for GH99 enzymes	1559:1610	This study has identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes.
29508463	7	11	theme	conserved	1463:1471	arg1	tyrosine					1485:1492	a conserved active site tyrosine	1461:1492	a conserved active site tyrosine	1461:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	3	12	theme	2-hydroxy	537:545	arg1	group					547:551	the 2-hydroxy group	533:551	the 2-hydroxy group adjacent to the fissile glycosidic bond	533:591	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	8	13	theme	mechanism-inspired	1559:1576	arg1	design					1588:1593	mechanism-inspired inhibitor design	1559:1593	mechanism-inspired inhibitor design for GH99 enzymes	1559:1610	This study has identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes.
29508463	3	14	theme	general	505:511	arg1	assistance					630:639	general acid assistance	617:639	general acid assistance	617:639	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	3	14	theme	general	505:511	arg1	base					513:516	a general base	503:516	a general base	503:516	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	3	14	theme	general	505:511	arg1	carboxylate					483:493	one carboxylate	479:493	one carboxylate	479:493	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	6	15	theme	general	1212:1218	arg1	base					1220:1223	the general base	1208:1223	the general base	1208:1223	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	5	16	theme	Modest	895:900	arg1	affinities					902:911	Modest affinities	895:911	Modest affinities	895:911	Modest affinities were observed for an endo-α-1,2-mannanase from Bacteroides thetaiotaomicron.
29508463	7	17	theme	active	1473:1478	arg1	tyrosine					1485:1492	a conserved active site tyrosine	1461:1492	a conserved active site tyrosine	1461:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	6	18	theme	failure	1159:1165	arg1	result					1147:1152	a result	1145:1152	a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2	1145:1348	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	6	18	theme	failure	1159:1165	arg1	inhibition					1104:1113	the poor inhibition	1095:1113	the poor inhibition shown by this compound	1095:1136	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	3	19	theme	fissile	569:575	arg1	bond					588:591	the fissile glycosidic bond	565:591	the fissile glycosidic bond	565:591	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	7	20	with	interaction	1444:1454	arg1	tyrosine					1485:1492	a conserved active site tyrosine	1461:1492	a conserved active site tyrosine	1461:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	2	21	theme	catalytic	436:444	arg1	carboxylates					446:457	two conserved catalytic carboxylates	422:457	two conserved catalytic carboxylates	422:457	They are proposed to act through a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates.
29508463	7	22	theme	site	1480:1483	arg1	tyrosine					1485:1492	a conserved active site tyrosine	1461:1492	a conserved active site tyrosine	1461:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	6	23	theme	nitrogen	1281:1288	arg1	basicity					1254:1261	basicity	1254:1261	basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2	1254:1348	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	5	24	from	thetaiotaomicron	972:987	arg1	endo-α-1,2-mannanase					934:953	an endo-α-1,2-mannanase	931:953	an endo-α-1,2-mannanase from Bacteroides thetaiotaomicron	931:987	Modest affinities were observed for an endo-α-1,2-mannanase from Bacteroides thetaiotaomicron.
29508463	4	25	theme	general	760:766	arg1	base					768:771	the general base	756:771	the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ)	756:830	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	2	26	theme	conserved	426:434	arg1	carboxylates					446:457	two conserved catalytic carboxylates	422:457	two conserved catalytic carboxylates	422:457	They are proposed to act through a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates.
29508463	6	27	theme	endocyclic	1270:1279	arg1	nitrogen					1281:1288	the endocyclic nitrogen	1266:1288	the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2	1266:1348	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	2	28	theme	two-step	337:344	arg1	mechanism					346:354	a two-step mechanism	335:354	a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates	335:457	They are proposed to act through a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates.
29508463	1	29	theme	α-Glc/Man-1,3-α-Man-OR	199:220	arg1	structures					222:231	α-Glc/Man-1,3-α-Man-OR structures	199:231	α-Glc/Man-1,3-α-Man-OR structures	199:231	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	6	30	from	C2	1347:1348	arg1	introduction					1300:1311	introduction	1300:1311	introduction of a vicinal, protonated amine at C2	1300:1348	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	4	31	theme	general	839:845	arg1	acid					847:850	the general acid	835:850	the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm)	835:892	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	6	32	theme	expected	1182:1189	arg1	interaction					1191:1201	the expected interaction	1178:1201	the expected interaction with the general base	1178:1223	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	4	33	dep	acid	847:850	arg1	ManManIm					884:891	ManManIm	884:891	ManManIm	884:891	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	4	33	dep	acid	847:850	arg1	α-mannosyl-1,3-mannoimidazole					853:881	α-mannosyl-1,3-mannoimidazole	853:881	α-mannosyl-1,3-mannoimidazole	853:881	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	0	34	theme	Strategies	15:24	arg1	Exploration					0:10	Exploration	0:10	Exploration of Strategies for Mechanism-Based Inhibitor Design for Family GH99	0:77	Exploration of Strategies for Mechanism-Based Inhibitor Design for Family GH99 endo-α-1,2-Mannanases.
29508463	6	35	theme	Man2NH2	1023:1029	arg1	DMJ					1031:1033	Man2NH2 DMJ	1023:1033	Man2NH2 DMJ	1023:1033	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	7	36	theme	interaction	1444:1454	arg1	downwards					1405:1413	the imidazole headgroup distorted downwards	1371:1413	the imidazole headgroup distorted downwards	1371:1413	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	7	36	theme	interaction	1444:1454	arg1	result					1418:1423	a result	1416:1423	a result of an unfavourable interaction with a conserved active site tyrosine	1416:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	4	37	theme	inhibitors	712:721	arg1	synthesis					695:703	the synthesis	691:703	the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm)	691:892	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	1	38	theme	family	174:179	arg1	members					143:149	members	143:149	members of glycoside hydrolase family 99 (GH99)	143:189	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	1	38	theme	family	174:179	arg1	endo-α-1,2-Mannosidases					102:124	endo-α-1,2-Mannosidases	102:124	endo-α-1,2-Mannosidases	102:124	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	0	39	theme	Inhibitor	46:54	arg1	Design					56:61	Mechanism-Based Inhibitor Design	30:61	Mechanism-Based Inhibitor Design	30:61	Exploration of Strategies for Mechanism-Based Inhibitor Design for Family GH99 endo-α-1,2-Mannanases.
29508463	4	40	dep	base	768:771	arg1	DMJ					827:829	Man2NH2 DMJ	819:829	Man2NH2 DMJ	819:829	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	4	40	dep	base	768:771	arg1	2-aminodeoxymannojirimycin					790:815	2-aminodeoxymannojirimycin	790:815	2-aminodeoxymannojirimycin	790:815	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	4	40	dep	base	768:771	arg1	α-mannosyl-1,3-					774:788	α-mannosyl-1,3-	774:788	α-mannosyl-1,3-(2-aminodeoxymannojirimycin)	774:816	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	6	41	theme	poor	1099:1102	arg1	inhibition					1104:1113	the poor inhibition	1095:1113	the poor inhibition shown by this compound	1095:1136	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	6	41	theme	poor	1099:1102	arg1	result					1147:1152	a result	1145:1152	a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2	1145:1348	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	3	42	theme	acid	625:628	arg1	carboxylate					483:493	one carboxylate	479:493	one carboxylate	479:493	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	3	42	theme	acid	625:628	arg1	base					513:516	a general base	503:516	a general base	503:516	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	3	42	theme	acid	625:628	arg1	assistance					630:639	general acid assistance	617:639	general acid assistance	617:639	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	1	43	theme	mammalian	240:248	arg1	glycans					259:265	mammalian N-linked glycans	240:265	mammalian N-linked glycans	240:265	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	0	44	theme	Mechanism-Based	30:44	arg1	Design					56:61	Mechanism-Based Inhibitor Design	30:61	Mechanism-Based Inhibitor Design	30:61	Exploration of Strategies for Mechanism-Based Inhibitor Design for Family GH99 endo-α-1,2-Mannanases.
29508463	3	45	theme	first	467:471	arg1	step					473:476	the first step	463:476	the first step	463:476	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	1	46	theme	N-linked	250:257	arg1	glycans					259:265	mammalian N-linked glycans	240:265	mammalian N-linked glycans	240:265	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	3	47	theme	aglycon	665:671	arg1	departure					648:656	the departure	644:656	the departure of the aglycon	644:671	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	7	48	theme	distorted	1395:1403	arg1	downwards					1405:1413	the imidazole headgroup distorted downwards	1371:1413	the imidazole headgroup distorted downwards	1371:1413	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	7	48	theme	distorted	1395:1403	arg1	result					1418:1423	a result	1416:1423	a result of an unfavourable interaction with a conserved active site tyrosine	1416:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	6	49	theme	Structural	990:999	arg1	studies					1001:1007	Structural studies	990:1007	Structural studies	990:1007	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	6	50	theme	amine	1338:1342	arg1	introduction					1300:1311	introduction	1300:1311	introduction of a vicinal, protonated amine at C2	1300:1348	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	3	51	theme	general	617:623	arg1	carboxylate					483:493	one carboxylate	479:493	one carboxylate	479:493	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	3	51	theme	general	617:623	arg1	base					513:516	a general base	503:516	a general base	503:516	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	3	51	theme	general	617:623	arg1	assistance					630:639	general acid assistance	617:639	general acid assistance	617:639	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	2	52	theme	1,2-anhydrosugar	368:383	arg1	intermediate					395:406	a 1,2-anhydrosugar "epoxide" intermediate	366:406	a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates	366:457	They are proposed to act through a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates.
29508463	8	53	contain	has	1506:1508	arg1	study					1500:1504	This study	1495:1504	This study	1495:1504	This study has identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes.
29508463	8	53	contain	has	1506:1508	arg2	limitations					1531:1541	identified important limitations	1510:1541	identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes	1510:1610	This study has identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes.
29508463	6	54	with	interaction	1191:1201	arg1	base					1220:1223	the general base	1208:1223	the general base	1208:1223	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	6	55	theme	protonated	1327:1336	arg1	amine					1338:1342	a vicinal, protonated amine	1316:1342	amine	1338:1342	Structural studies revealed that Man2NH2 DMJ binds like other iminosugar inhibitors, which suggests that the poor inhibition shown by this compound is not a result of a failure to achieve the expected interaction with the general base, but rather the reduction in basicity of the endocyclic nitrogen caused by introduction of a vicinal, protonated amine at C2.
29508463	7	56	theme	imidazole	1375:1383	arg1	downwards					1405:1413	the imidazole headgroup distorted downwards	1371:1413	the imidazole headgroup distorted downwards	1371:1413	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	7	56	theme	imidazole	1375:1383	arg1	result					1418:1423	a result	1416:1423	a result of an unfavourable interaction with a conserved active site tyrosine	1416:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	4	57	theme	Man2NH2	819:825	arg1	DMJ					827:829	Man2NH2 DMJ	819:829	Man2NH2 DMJ	819:829	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	4	57	theme	Man2NH2	819:825	arg1	α-mannosyl-1,3-					774:788	α-mannosyl-1,3-	774:788	α-mannosyl-1,3-(2-aminodeoxymannojirimycin)	774:816	We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxymannojirimycin), Man2NH2 DMJ) or the general acid (α-mannosyl-1,3-mannoimidazole, ManManIm).
29508463	1	58	theme	glycoside	154:162	arg1	family					174:179	glycoside hydrolase family 99	154:182	glycoside hydrolase family 99 (GH99)	154:189	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	1	58	theme	glycoside	154:162	arg1	GH99					185:188	GH99	185:188	GH99	185:188	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	8	59	theme	identified	1510:1519	arg1	limitations					1531:1541	identified important limitations	1510:1541	identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes	1510:1610	This study has identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes.
29508463	7	60	theme	headgroup	1385:1393	arg1	downwards					1405:1413	the imidazole headgroup distorted downwards	1371:1413	the imidazole headgroup distorted downwards	1371:1413	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	7	60	theme	headgroup	1385:1393	arg1	result					1418:1423	a result	1416:1423	a result of an unfavourable interaction with a conserved active site tyrosine	1416:1492	ManManIm binds with the imidazole headgroup distorted downwards, a result of an unfavourable interaction with a conserved active site tyrosine.
29508463	1	61	theme	hydrolase	164:172	arg1	family					174:179	glycoside hydrolase family 99	154:182	glycoside hydrolase family 99 (GH99)	154:189	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	1	61	theme	hydrolase	164:172	arg1	GH99					185:188	GH99	185:188	GH99	185:188	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
29508463	5	62	theme	Bacteroides	960:970	arg1	thetaiotaomicron					972:987	Bacteroides thetaiotaomicron	960:987	Bacteroides thetaiotaomicron	960:987	Modest affinities were observed for an endo-α-1,2-mannanase from Bacteroides thetaiotaomicron.
29508463	8	63	theme	GH99	1599:1602	arg1	enzymes					1604:1610	GH99 enzymes	1599:1610	GH99 enzymes	1599:1610	This study has identified important limitations associated with mechanism-inspired inhibitor design for GH99 enzymes.
29508463	3	64	theme	adjacent	553:560	arg1	group					547:551	the 2-hydroxy group	533:551	the 2-hydroxy group adjacent to the fissile glycosidic bond	533:591	In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon.
29508463	1	65	theme	fungal	271:276	arg1	α-mannan					278:285	fungal α-mannan	271:285	fungal α-mannan	271:285	endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively.
31866443	8	0	theme	nuclear	1118:1124	arg1	proteins					1126:1133	nuclear proteins	1118:1133	nuclear proteins	1118:1133	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	1	1	theme	white	154:158	arg1	tissue					168:173	white adipose tissue	154:173	white adipose tissue (WAT)	154:179	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	8	2	theme	transcriptional	1159:1173	arg1	response					1175:1182	a pro-inflammatory transcriptional response	1140:1182	a pro-inflammatory transcriptional response	1140:1182	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	5	3	theme	protein	596:602	arg1	levels					604:609	both pro-inflammatory gene and protein levels	565:609	levels	604:609	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31866443	1	4	theme	adipose	160:166	arg1	tissue					168:173	white adipose tissue	154:173	white adipose tissue (WAT)	154:179	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	1	5	attach	linked	128:133	arg2	complications					110:122	associated metabolic complications	89:122	associated metabolic complications	89:122	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	1	5	attach	linked	128:133	arg2	obesity					77:83	obesity	77:83	obesity	77:83	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	1	5	attach	linked	128:133	arg1	inflammation					138:149	inflammation	138:149	inflammation of white adipose tissue (WAT)	138:179	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	0	6	attach	Links	10:14	arg2	Glutamine					0:8	Glutamine	0:8	Glutamine	0:8	Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.
31866443	0	6	attach	Links	10:14	arg1	Inflammation					27:38	Inflammation	27:38	Inflammation	27:38	Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.
31866443	8	7	theme	pro-inflammatory	1142:1157	arg1	response					1175:1182	a pro-inflammatory transcriptional response	1140:1182	a pro-inflammatory transcriptional response	1140:1182	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	7	8	dep	modification	902:913	arg1	O-GlcNAc					947:954	O-GlcNAc	947:954	O-GlcNAc	947:954	UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.
31866443	7	8	dep	modification	902:913	arg1	β-N-acetylglucosamine					924:944	β-N-acetylglucosamine	924:944	the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase	879:999	UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.
31866443	7	9	theme	O-linked	915:922	arg1	modification					902:913	the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	879:955	the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase	879:999	UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.
31866443	8	10	theme	reduced	1080:1086	arg1	glutamine					1088:1096	reduced glutamine	1080:1096	reduced glutamine	1080:1096	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	6	11	from	analyses	698:705	arg1	adipocytes					716:725	human adipocytes	710:725	human adipocytes	710:725	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	1	12	theme	tissue	168:173	arg1	inflammation					138:149	inflammation	138:149	inflammation of white adipose tissue (WAT)	138:179	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	7	13	link	O-linked	915:922	arg1	modification					902:913	the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	879:955	the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase	879:999	UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.
31866443	6	14	theme	UDP-GlcNAc	827:836	arg1	levels					839:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	2	15	theme	metabolic	248:256	arg1	determinant					292:302	an important determinant	279:302	an important determinant	279:302	We hypothesized that the local metabolic environment could be an important determinant.
31866443	2	15	theme	metabolic	248:256	arg1	environment					258:268	the local metabolic environment	238:268	the local metabolic environment	238:268	We hypothesized that the local metabolic environment could be an important determinant.
31866443	6	16	theme	human	710:714	arg1	adipocytes					716:725	human adipocytes	710:725	human adipocytes	710:725	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	5	17	dep	WAT	664:666	arg1	in					661:662	in	661:662	in	661:662	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31866443	8	18	theme	proteins	1126:1133	arg1	glutamine					1088:1096	reduced glutamine	1080:1096	reduced glutamine	1080:1096	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	8	18	theme	proteins	1126:1133	arg1	response					1175:1182	a pro-inflammatory transcriptional response	1140:1182	a pro-inflammatory transcriptional response	1140:1182	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	8	18	theme	proteins	1126:1133	arg1	O-GlcNAcylation					1099:1113	O-GlcNAcylation	1099:1113	O-GlcNAcylation of nuclear proteins	1099:1133	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	5	19	theme	pro-inflammatory	570:585	arg1	gene					587:590	both pro-inflammatory gene and protein levels	565:609	gene	587:590	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31866443	5	20	theme	macrophage	637:646	arg1	infiltration					648:659	and macrophage infiltration	633:659	infiltration	648:659	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31866443	9	21	theme	glutamine	1197:1205	arg1	metabolism					1207:1216	glutamine metabolism	1197:1216	glutamine metabolism	1197:1216	Altogether, glutamine metabolism is linked to WAT inflammation in obesity.
31866443	5	22	dep	infiltration	648:659	arg1	WAT					664:666	WAT	664:666	WAT	664:666	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31866443	6	23	theme	N-acetylglucosamine	806:824	arg1	levels					839:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	2	24	theme	important	282:290	arg1	determinant					292:302	an important determinant	279:302	an important determinant	279:302	We hypothesized that the local metabolic environment could be an important determinant.
31866443	2	24	theme	important	282:290	arg1	environment					258:268	the local metabolic environment	238:268	the local metabolic environment	238:268	We hypothesized that the local metabolic environment could be an important determinant.
31866443	6	25	theme	bioenergetic	685:696	arg1	analyses					698:705	Metabolomic and bioenergetic analyses	669:705	Metabolomic and bioenergetic analyses in human adipocytes	669:725	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	9	26	from	inflammation	1235:1246	arg1	obesity					1251:1257	obesity	1251:1257	obesity	1251:1257	Altogether, glutamine metabolism is linked to WAT inflammation in obesity.
31866443	1	27	theme	metabolic	100:108	arg1	complications					110:122	associated metabolic complications	89:122	associated metabolic complications	89:122	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	5	28	from	levels	604:609	arg1	adipocytes					614:623	adipocytes	614:623	adipocytes	614:623	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31866443	3	29	theme	non-obese	376:384	arg1	women					386:390	81 obese and non-obese women	363:390	81 obese and non-obese women	363:390	To this end, we compared metabolites released from WAT of 81 obese and non-obese women.
31866443	8	30	theme	mechanistic	1055:1065	arg1	link					1067:1070	a mechanistic link	1053:1070	a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response	1053:1182	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	6	31	theme	Metabolomic	669:679	arg1	analyses					698:705	Metabolomic and bioenergetic analyses	669:705	Metabolomic and bioenergetic analyses in human adipocytes	669:725	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	1	32	theme	causal	186:191	arg1	factors					193:199	the causal factors	182:199	the causal factors	182:199	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	8	33	from	studies	1013:1019	arg1	adipocytes					1030:1039	human adipocytes	1024:1039	human adipocytes	1024:1039	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	6	34	theme	diphosphate	794:804	arg1	levels					839:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	3	35	theme	obese	366:370	arg1	women					386:390	81 obese and non-obese women	363:390	81 obese and non-obese women	363:390	To this end, we compared metabolites released from WAT of 81 obese and non-obese women.
31866443	0	36	theme	Adipose	55:61	arg1	Tissue					63:68	Human White Adipose Tissue	43:68	Human White Adipose Tissue	43:68	Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.
31866443	6	37	theme	uridine	786:792	arg1	levels					839:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels	786:844	Metabolomic and bioenergetic analyses in human adipocytes suggested that glutamine attenuated glycolysis and reduced uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) levels.
31866443	5	38	from	gene	587:590	arg1	adipocytes					614:623	adipocytes	614:623	adipocytes	614:623	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31866443	0	39	theme	Human	43:47	arg1	Tissue					63:68	Human White Adipose Tissue	43:68	Human White Adipose Tissue	43:68	Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.
31866443	7	40	theme	enzyme	973:978	arg1	transferase					989:999	the enzyme O-GlcNAc transferase	969:999	the enzyme O-GlcNAc transferase	969:999	UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.
31866443	9	41	attach	linked	1221:1226	arg1	inflammation					1235:1246	WAT inflammation	1231:1246	WAT inflammation in obesity	1231:1257	Altogether, glutamine metabolism is linked to WAT inflammation in obesity.
31866443	9	41	attach	linked	1221:1226	arg2	metabolism					1207:1216	glutamine metabolism	1197:1216	glutamine metabolism	1197:1216	Altogether, glutamine metabolism is linked to WAT inflammation in obesity.
31866443	2	42	theme	local	242:246	arg1	determinant					292:302	an important determinant	279:302	an important determinant	279:302	We hypothesized that the local metabolic environment could be an important determinant.
31866443	2	42	theme	local	242:246	arg1	environment					258:268	the local metabolic environment	238:268	the local metabolic environment	238:268	We hypothesized that the local metabolic environment could be an important determinant.
31866443	8	43	theme	Functional	1002:1011	arg1	studies					1013:1019	Functional studies	1002:1019	Functional studies in human adipocytes	1002:1039	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	1	44	theme	associated	89:98	arg1	complications					110:122	associated metabolic complications	89:122	associated metabolic complications	89:122	While obesity and associated metabolic complications are linked to inflammation of white adipose tissue (WAT), the causal factors remain unclear.
31866443	9	45	theme	WAT	1231:1233	arg1	inflammation					1235:1246	WAT inflammation	1231:1246	WAT inflammation in obesity	1231:1257	Altogether, glutamine metabolism is linked to WAT inflammation in obesity.
31866443	8	46	theme	human	1024:1028	arg1	adipocytes					1030:1039	human adipocytes	1024:1039	human adipocytes	1024:1039	Functional studies in human adipocytes established a mechanistic link between reduced glutamine, O-GlcNAcylation of nuclear proteins, and a pro-inflammatory transcriptional response.
31866443	7	47	theme	post-translational	883:900	arg1	modification					902:913	the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	879:955	the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase	879:999	UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.
31866443	7	48	theme	O-GlcNAc	980:987	arg1	transferase					989:999	the enzyme O-GlcNAc transferase	969:999	the enzyme O-GlcNAc transferase	969:999	UDP-GlcNAc is the substrate for the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) mediated by the enzyme O-GlcNAc transferase.
31866443	0	49	theme	White	49:53	arg1	Tissue					63:68	Human White Adipose Tissue	43:68	Human White Adipose Tissue	43:68	Glutamine Links Obesity to Inflammation in Human White Adipose Tissue.
31866443	5	50	theme	Glutamine	508:516	arg1	administration					518:531	Glutamine administration in vitro	508:540	Glutamine administration in vitro	508:540	Glutamine administration in vitro and in vivo attenuated both pro-inflammatory gene and protein levels in adipocytes and WAT and macrophage infiltration in WAT.
31336250	2	0	theme	production	619:628	arg1	absence					557:563	the absence	553:563	the absence of glycan heterogeneity and simple bacterial antibody production	553:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	1	theme	receptor	360:367	arg1	binding					376:382	abrogated Fc gamma receptor (FcγR) binding	341:382	abrogated Fc gamma receptor (FcγR) binding	341:382	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	1	2	theme	therapeutic	249:259	arg1	clearance					288:296	clearance	288:296	clearance of antibody-opsonized tumor cells	288:330	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	1	2	theme	therapeutic	249:259	arg1	functions					270:278	therapeutic effector functions	249:278	therapeutic effector functions such as clearance of antibody-opsonized tumor cells	249:330	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	2	3	theme	bacterial	600:608	arg1	production					619:628	simple bacterial antibody production	593:628	simple bacterial antibody production	593:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	6	4	gly	aglycosylated	1321:1333	arg1	variants					1338:1345	engineered aglycosylated Fc variants	1310:1345	engineered aglycosylated Fc variants	1310:1345	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	5	5	gly	glycosylated	1181:1192	arg1	Fc					1194:1195	wild-type glycosylated Fc	1171:1195	wild-type glycosylated Fc	1171:1195	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	1	6	theme	Fc	167:168	arg1	receptors					170:178	Fc receptors	167:178	Fc receptors expressed on the surfaces of various immune leukocytes	167:233	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	6	7	theme	aglycosylated	1220:1232	arg1	variant					1237:1243	this aglycosylated Fc variant	1215:1243	this aglycosylated Fc variant	1215:1243	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	8	gly	aglycosylated	1220:1232	arg1	variant					1237:1243	this aglycosylated Fc variant	1215:1243	this aglycosylated Fc variant	1215:1243	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	9	theme	Fc	1335:1336	arg1	variants					1338:1345	engineered aglycosylated Fc variants	1310:1345	engineered aglycosylated Fc variants	1310:1345	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	4	10	theme	human	946:950	arg1	FcγRs					952:956	human FcγRs	946:956	human FcγRs in previous studies	946:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	4	11	with	library	780:786	arg1	combinations					808:819	combinations	808:819	combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies	808:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	6	12	theme	beneficial	1432:1441	arg1	mutations					1443:1451	beneficial mutations	1432:1451	beneficial mutations	1432:1451	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	13	theme	aglycosylated	1321:1333	arg1	variants					1338:1345	engineered aglycosylated Fc variants	1310:1345	engineered aglycosylated Fc variants	1310:1345	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	2	14	theme	N-linked	436:443	arg1	glycosylation					445:457	N-linked glycosylation	436:457	N-linked glycosylation	436:457	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	4	15	theme	aglycosylated	918:930	arg1	regions					935:941	aglycosylated Fc regions	918:941	aglycosylated Fc regions	918:941	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	2	16	theme	glycan	568:573	arg1	heterogeneity					575:587	glycan heterogeneity	568:587	glycan heterogeneity	568:587	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	5	17	theme	Fc	1076:1077	arg1	variant					1079:1085	an aglycosylated Fc variant	1059:1085	an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc	1059:1195	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	4	18	theme	glycosylated	902:913	arg1	binding					891:897	binding	891:897	binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies	891:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	4	19	theme	regions	935:941	arg1	binding					891:897	binding	891:897	binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies	891:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	6	20	theme	beneficial	1285:1294	arg1	mutations					1296:1304	previously identified beneficial mutations	1263:1304	previously identified beneficial mutations for engineered aglycosylated Fc variants	1263:1345	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	1	21	theme	antibodies	130:139	arg1	crucial					144:150	crucial	144:150	crucial	144:150	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	1	21	theme	antibodies	130:139	arg1	region					116:121	The Fc region	109:121	The Fc region of IgG antibodies	109:139	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	2	22	theme	IgG	501:503	arg1	antibodies					505:514	IgG antibodies	501:514	IgG antibodies	501:514	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	0	23	theme	effector	62:69	arg1	function					71:78	ADCC effector function	57:78	ADCC effector function of aglycosylated antibodies	57:106	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	5	24	theme	glycosylated	1181:1192	arg1	Fc					1194:1195	wild-type glycosylated Fc	1171:1195	wild-type glycosylated Fc	1171:1195	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	4	25	gly	aglycosylated	918:930	arg1	regions					935:941	aglycosylated Fc regions	918:941	aglycosylated Fc regions	918:941	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	6	26	gly	glycosylated	1361:1372	arg1	variants					1374:1381	glycosylated variants	1361:1381	glycosylated variants	1361:1381	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	1	27	theme	Fc	113:114	arg1	crucial					144:150	crucial	144:150	crucial	144:150	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	1	27	theme	Fc	113:114	arg1	region					116:121	The Fc region	109:121	The Fc region of IgG antibodies	109:139	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	0	28	theme	antibodies	97:106	arg1	function					71:78	ADCC effector function	57:78	ADCC effector function of aglycosylated antibodies	57:106	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	5	29	theme	cell-mediated	1139:1151	arg1	cytotoxicity					1153:1164	the antibody-dependent cell-mediated cytotoxicity	1116:1164	almost double the antibody-dependent cell-mediated cytotoxicity	1102:1164	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	2	30	from	Asn297	462:467	arg1	binding					376:382	abrogated Fc gamma receptor (FcγR) binding	341:382	abrogated Fc gamma receptor (FcγR) binding	341:382	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	30	from	Asn297	462:467	arg1	function					409:416	therapeutic effector function	388:416	therapeutic effector function	388:416	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	4	31	theme	Fc	791:792	arg1	variants					794:801	Fc variants	791:801	Fc variants	791:801	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	2	32	theme	effector	400:407	arg1	function					409:416	therapeutic effector function	388:416	therapeutic effector function	388:416	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	0	33	gly	aglycosylated	83:95	arg1	antibodies					97:106	aglycosylated antibodies	83:106	aglycosylated antibodies	83:106	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	0	34	theme	Optimal	0:6	arg1	combination					8:18	Optimal combination	0:18	Optimal combination of beneficial mutations for	0:46	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	5	35	gly	aglycosylated	1062:1074	arg1	variant					1079:1085	an aglycosylated Fc variant	1059:1085	an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc	1059:1195	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	6	36	from	mutations	1202:1210	arg1	variant					1237:1243	this aglycosylated Fc variant	1215:1243	this aglycosylated Fc variant	1215:1243	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	5	37	theme	High-throughput	979:993	arg1	screening					995:1003	High-throughput screening	979:1003	High-throughput screening of the resulting library	979:1028	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	2	38	theme	aglycosylated	474:486	arg1	region					491:496	the aglycosylated Fc region	470:496	the aglycosylated Fc region of IgG antibodies	470:514	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	4	39	theme	beneficial	827:836	arg1	mutations					838:846	25 beneficial mutations	824:846	25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies	824:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	0	40	theme	mutations	34:42	arg1	combination					8:18	Optimal combination	0:18	Optimal combination of beneficial mutations for	0:46	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	1	41	theme	antibody-opsonized	301:318	arg1	cells					326:330	antibody-opsonized tumor cells	301:330	antibody-opsonized tumor cells	301:330	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	2	42	gly	aglycosylated	474:486	arg1	region					491:496	the aglycosylated Fc region	470:496	the aglycosylated Fc region of IgG antibodies	470:514	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	43	theme	gamma	354:358	arg1	FcγR					370:373	FcγR	370:373	FcγR	370:373	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	43	theme	gamma	354:358	arg1	receptor					360:367	Fc gamma receptor	351:367	abrogated Fc gamma receptor (FcγR) binding	341:382	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	6	44	theme	aglycosylated	1503:1515	arg1	Fc					1517:1518	aglycosylated Fc	1503:1518	aglycosylated Fc	1503:1518	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	1	45	theme	cells	326:330	arg1	clearance					288:296	clearance	288:296	clearance of antibody-opsonized tumor cells	288:330	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	5	46	theme	aglycosylated	1062:1074	arg1	variant					1079:1085	an aglycosylated Fc variant	1059:1085	an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc	1059:1195	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	3	47	theme	functional	708:717	arg1	units					719:723	effector functional units	699:723	effector functional units for human therapy	699:741	Therefore, these antibodies have been comprehensively engineered as effector functional units for human therapy.
31336250	3	47	theme	functional	708:717	arg1	antibodies					648:657	these antibodies	642:657	these antibodies	642:657	Therefore, these antibodies have been comprehensively engineered as effector functional units for human therapy.
31336250	2	48	theme	abrogated	341:349	arg1	binding					376:382	abrogated Fc gamma receptor (FcγR) binding	341:382	abrogated Fc gamma receptor (FcγR) binding	341:382	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	1	49	theme	various	209:215	arg1	leukocytes					224:233	various immune leukocytes	209:233	various immune leukocytes	209:233	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	2	50	contain	has	516:518	arg2	advantages					534:543	bioprocessing advantages	520:543	bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production	520:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	50	contain	has	516:518	arg2	absence					557:563	the absence	553:563	the absence of glycan heterogeneity and simple bacterial antibody production	553:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	50	contain	has	516:518	arg1	region					491:496	the aglycosylated Fc region	470:496	the aglycosylated Fc region of IgG antibodies	470:514	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	1	51	theme	leukocytes	224:233	arg1	surfaces					197:204	the surfaces	193:204	the surfaces of various immune leukocytes	193:233	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	0	52	theme	ADCC	57:60	arg1	function					71:78	ADCC effector function	57:78	ADCC effector function of aglycosylated antibodies	57:106	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	6	53	theme	effector	1482:1489	arg1	function					1491:1498	the effector function	1478:1498	the effector function of aglycosylated Fc	1478:1518	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	2	54	theme	antibody	610:617	arg1	production					619:628	simple bacterial antibody production	593:628	simple bacterial antibody production	593:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	6	55	theme	glycosylated	1361:1372	arg1	variants					1374:1381	glycosylated variants	1361:1381	glycosylated variants	1361:1381	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	1	56	theme	effector	261:268	arg1	clearance					288:296	clearance	288:296	clearance of antibody-opsonized tumor cells	288:330	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	1	56	theme	effector	261:268	arg1	functions					270:278	therapeutic effector functions	249:278	therapeutic effector functions such as clearance of antibody-opsonized tumor cells	249:330	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	2	57	theme	simple	593:598	arg1	production					619:628	simple bacterial antibody production	593:628	simple bacterial antibody production	593:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	6	58	theme	Fc	1234:1235	arg1	variant					1237:1243	this aglycosylated Fc variant	1215:1243	this aglycosylated Fc variant	1215:1243	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	59	theme	mutations	1443:1451	arg1	sets					1424:1427	significantly different sets	1400:1427	significantly different sets of beneficial mutations	1400:1451	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	59	theme	mutations	1443:1451	arg1	mutations					1443:1451	beneficial mutations	1432:1451	beneficial mutations	1432:1451	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	4	60	from	FcγRs	952:956	arg1	studies					970:976	previous studies	961:976	previous studies	961:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	6	61	theme	engineered	1310:1319	arg1	variants					1338:1345	engineered aglycosylated Fc variants	1310:1345	engineered aglycosylated Fc variants	1310:1345	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	62	theme	different	1414:1422	arg1	sets					1424:1427	significantly different sets	1400:1427	significantly different sets of beneficial mutations	1400:1451	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	62	theme	different	1414:1422	arg1	mutations					1443:1451	beneficial mutations	1432:1451	beneficial mutations	1432:1451	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	5	63	theme	antibody-dependent	1120:1137	arg1	cytotoxicity					1153:1164	the antibody-dependent cell-mediated cytotoxicity	1116:1164	almost double the antibody-dependent cell-mediated cytotoxicity	1102:1164	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	2	64	theme	heterogeneity	575:587	arg1	absence					557:563	the absence	553:563	the absence of glycan heterogeneity and simple bacterial antibody production	553:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	5	65	theme	variant	1079:1085	arg1	identification					1041:1054	the identification	1037:1054	the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc	1037:1195	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	1	66	theme	IgG	126:128	arg1	antibodies					130:139	IgG antibodies	126:139	IgG antibodies	126:139	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	4	67	theme	Fc	932:933	arg1	regions					935:941	aglycosylated Fc regions	918:941	aglycosylated Fc regions	918:941	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	6	68	theme	identified	1274:1283	arg1	mutations					1296:1304	previously identified beneficial mutations	1263:1304	previously identified beneficial mutations for engineered aglycosylated Fc variants	1263:1345	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	2	69	theme	bioprocessing	520:532	arg1	absence					557:563	the absence	553:563	the absence of glycan heterogeneity and simple bacterial antibody production	553:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	69	theme	bioprocessing	520:532	arg1	advantages					534:543	bioprocessing advantages	520:543	bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production	520:628	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	0	70	theme	aglycosylated	83:95	arg1	antibodies					97:106	aglycosylated antibodies	83:106	aglycosylated antibodies	83:106	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	2	71	theme	Fc	488:489	arg1	region					491:496	the aglycosylated Fc region	470:496	the aglycosylated Fc region of IgG antibodies	470:514	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	72	link	N-linked	436:443	arg1	glycosylation					445:457	N-linked glycosylation	436:457	N-linked glycosylation	436:457	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	6	73	attach	derived	1250:1256	arg2	mutations					1202:1210	All mutations	1198:1210	All mutations in this aglycosylated Fc variant	1198:1243	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	6	73	attach	derived	1250:1256	arg1	mutations					1296:1304	previously identified beneficial mutations	1263:1304	previously identified beneficial mutations for engineered aglycosylated Fc variants	1263:1345	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	4	74	theme	previous	961:968	arg1	studies					970:976	previous studies	961:976	previous studies	961:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	4	75	theme	huge	775:778	arg1	library					780:786	a huge library	773:786	a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies	773:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	6	76	gly	aglycosylated	1503:1515	arg1	Fc					1517:1518	aglycosylated Fc	1503:1518	aglycosylated Fc	1503:1518	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	2	77	theme	antibodies	505:514	arg1	region					491:496	the aglycosylated Fc region	470:496	the aglycosylated Fc region of IgG antibodies	470:514	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	78	theme	therapeutic	388:398	arg1	function					409:416	therapeutic effector function	388:416	therapeutic effector function	388:416	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	5	79	theme	wild-type	1171:1179	arg1	Fc					1194:1195	wild-type glycosylated Fc	1171:1195	wild-type glycosylated Fc	1171:1195	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	2	80	theme	glycosylation	445:457	arg1	absence					425:431	the absence	421:431	the absence of N-linked glycosylation	421:457	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	5	81	theme	double	1109:1114	arg1	cytotoxicity					1153:1164	the antibody-dependent cell-mediated cytotoxicity	1116:1164	almost double the antibody-dependent cell-mediated cytotoxicity	1102:1164	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	0	82	theme	beneficial	23:32	arg1	mutations					34:42	beneficial mutations	23:42	beneficial mutations for	23:46	Optimal combination of beneficial mutations for improved ADCC effector function of aglycosylated antibodies.
31336250	6	83	theme	Fc	1517:1518	arg1	function					1491:1498	the effector function	1478:1498	the effector function of aglycosylated Fc	1478:1518	All mutations in this aglycosylated Fc variant were derived from previously identified beneficial mutations for engineered aglycosylated Fc variants as opposed to glycosylated variants, suggesting that significantly different sets of beneficial mutations are necessary to improve the effector function of aglycosylated Fc.
31336250	1	84	theme	tumor	320:324	arg1	cells					326:330	antibody-opsonized tumor cells	301:330	antibody-opsonized tumor cells	301:330	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	2	85	from	binding	376:382	arg1	absence					425:431	the absence	421:431	the absence of N-linked glycosylation	421:457	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	3	86	theme	effector	699:706	arg1	units					719:723	effector functional units	699:723	effector functional units for human therapy	699:741	Therefore, these antibodies have been comprehensively engineered as effector functional units for human therapy.
31336250	3	86	theme	effector	699:706	arg1	antibodies					648:657	these antibodies	642:657	these antibodies	642:657	Therefore, these antibodies have been comprehensively engineered as effector functional units for human therapy.
31336250	4	87	theme	mutations	838:846	arg1	combinations					808:819	combinations	808:819	combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies	808:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	2	88	theme	Fc	351:352	arg1	FcγR					370:373	FcγR	370:373	FcγR	370:373	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	2	88	theme	Fc	351:352	arg1	receptor					360:367	Fc gamma receptor	351:367	abrogated Fc gamma receptor (FcγR) binding	341:382	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	5	89	theme	library	1022:1028	arg1	screening					995:1003	High-throughput screening	979:1003	High-throughput screening of the resulting library	979:1028	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	5	90	theme	resulting	1012:1020	arg1	library					1022:1028	the resulting library	1008:1028	the resulting library	1008:1028	High-throughput screening of the resulting library led to the identification of an aglycosylated Fc variant that exhibited almost double the antibody-dependent cell-mediated cytotoxicity than wild-type glycosylated Fc.
31336250	4	91	theme	variants	794:801	arg1	library					780:786	a huge library	773:786	a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies	773:976	In this work, we constructed a huge library of Fc variants with combinations of 25 beneficial mutations that were previously identified to improve binding of glycosylated or aglycosylated Fc regions to human FcγRs in previous studies.
31336250	1	92	theme	immune	217:222	arg1	leukocytes					224:233	various immune leukocytes	209:233	various immune leukocytes	209:233	The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells.
31336250	2	93	from	function	409:416	arg1	absence					425:431	the absence	421:431	the absence of N-linked glycosylation	421:457	Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the absence of N-linked glycosylation at Asn297, the aglycosylated Fc region of IgG antibodies has bioprocessing advantages such as the absence of glycan heterogeneity and simple bacterial antibody production.
31336250	3	94	theme	human	729:733	arg1	therapy					735:741	human therapy	729:741	human therapy	729:741	Therefore, these antibodies have been comprehensively engineered as effector functional units for human therapy.
30359584	0	0	theme	cultured	73:80	arg1	cells					82:86	cultured cells	73:86	cultured cells	73:86	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	0	1	from	acids	10:14	arg1	tissues					61:67	mammalian tissues	51:67	mammalian tissues	51:67	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	0	1	from	acids	10:14	arg1	cells					82:86	cultured cells	73:86	cultured cells	73:86	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	3	2	from	study	397:401	arg1	tissue					465:470	adipose tissue	457:470	adipose tissue	457:470	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	2	from	study	397:401	arg1	serum					496:500	blood serum	490:500	blood serum	490:500	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	2	from	study	397:401	arg1	liver					473:477	liver	473:477	liver	473:477	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	2	from	study	397:401	arg1	brain					480:484	brain	480:484	brain	480:484	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	2	from	study	397:401	arg1	cultures					551:558	cell cultures	546:558	cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes)	546:688	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	2	from	study	397:401	arg1	tissues					448:454	different mammalian tissues	428:454	different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog)	428:529	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	2	3	theme	important	310:318	arg1	messenger					343:351	a lipid second messenger	328:351	a lipid second messenger	328:351	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	2	3	theme	important	310:318	arg1	role					320:323	an important role	307:323	an important role	307:323	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	3	4	theme	spectrometry	775:786	arg1	platform					809:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	5	theme	primary	581:587	arg1	hepatocytes					589:599	primary hepatocytes	581:599	primary hepatocytes	581:599	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	6	theme	mammalian	563:571	arg1	origin					573:578	mammalian origin	563:578	mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes)	563:688	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	1	7	theme	sphingoid	160:168	arg1	base					170:173	a sphingoid base	158:173	a sphingoid base N-linked to a fatty acyl chain	158:204	Sphingolipids consist of a sphingoid base N-linked to a fatty acyl chain.
30359584	3	8	theme	ultra-high	699:708	arg1	chromatography					729:742	an ultra-high performance liquid chromatography	696:742	an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	696:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	9	theme	origin	573:578	arg1	cultures					551:558	cell cultures	546:558	cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes)	546:688	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	4	10	from	samples	915:921	arg1	results					893:899	results	893:899	results from 20 other samples	893:921	The data have been compared with published, in general semi-quantitative, results from 20 other samples, with good agreement.
30359584	2	11	theme	mammalian	263:271	arg1	cells					273:277	mammalian cells	263:277	mammalian cells	263:277	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	3	12	theme	blood	490:494	arg1	serum					496:500	blood serum	490:500	blood serum	490:500	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	12	theme	blood	490:494	arg1	tissues					448:454	different mammalian tissues	428:454	different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog)	428:529	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	6	13	theme	fatty	1050:1054	arg1	different					1091:1099	different	1091:1099	different	1091:1099	The fatty acid composition of SM was clearly different from that of Cer.
30359584	6	13	theme	fatty	1050:1054	arg1	composition					1061:1071	The fatty acid composition	1046:1071	The fatty acid composition of SM	1046:1077	The fatty acid composition of SM was clearly different from that of Cer.
30359584	3	14	theme	immortalized	602:613	arg1	cells					620:624	immortalized MDCK cells	602:624	immortalized MDCK cells	602:624	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	15	theme	time-of-flight	755:768	arg1	platform					809:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	16	theme	MDCK	615:618	arg1	cells					620:624	immortalized MDCK cells	602:624	immortalized MDCK cells	602:624	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	17	theme	SM	414:415	arg1	species					417:423	Cer and SM species	406:423	species	417:423	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	18	theme	-based	802:807	arg1	platform					809:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	19	theme	lipidomic	387:395	arg1	study					397:401	a quantitative lipidomic study	372:401	a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes)	372:688	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	0	20	theme	Biophysical	89:99	arg1	implications					119:130	Biophysical and physiological implications	89:130	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.	0:131	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	2	21	theme	major	243:247	arg1	sphingomyelins					219:232	sphingomyelins	219:232	sphingomyelins (SM)	219:237	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	2	21	theme	major	243:247	arg1	components					249:258	major components	243:258	major components of mammalian cells	243:277	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	5	22	theme	d18-1	982:986	arg1	sphingosine					988:998	d18-1 sphingosine	982:998	d18-1 sphingosine (2-amino-4-octadecene-1,3-diol)	982:1030	The sphingoid base was predominantly d18-1 sphingosine (2-amino-4-octadecene-1,3-diol) in all cases.
30359584	5	22	theme	d18-1	982:986	arg1	base					959:962	The sphingoid base	945:962	The sphingoid base	945:962	The sphingoid base was predominantly d18-1 sphingosine (2-amino-4-octadecene-1,3-diol) in all cases.
30359584	5	22	theme	d18-1	982:986	arg1	2-amino-4-octadecene-1,3-diol					1001:1029	2-amino-4-octadecene-1,3-diol	1001:1029	2-amino-4-octadecene-1,3-diol	1001:1029	The sphingoid base was predominantly d18-1 sphingosine (2-amino-4-octadecene-1,3-diol) in all cases.
30359584	1	23	theme	N-linked	175:182	arg1	base					170:173	a sphingoid base	158:173	a sphingoid base N-linked to a fatty acyl chain	158:204	Sphingolipids consist of a sphingoid base N-linked to a fatty acyl chain.
30359584	0	24	theme	fatty	4:8	arg1	acids					10:14	The fatty acids	0:14	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.	0:131	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	3	25	dep	tissues	448:454	arg1	brain					480:484	brain	480:484	brain	480:484	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	25	dep	tissues	448:454	arg1	serum					496:500	blood serum	490:500	blood serum	490:500	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	25	dep	tissues	448:454	arg1	liver					473:477	liver	473:477	liver	473:477	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	25	dep	tissues	448:454	arg1	tissues					448:454	different mammalian tissues	428:454	different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog)	428:529	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	25	dep	tissues	448:454	arg1	tissue					465:470	adipose tissue	457:470	adipose tissue	457:470	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	26	theme	UHPLC-ToF-MS	789:800	arg1	platform					809:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	2	27	theme	lipid	330:334	arg1	messenger					343:351	a lipid second messenger	328:351	a lipid second messenger	328:351	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	2	27	theme	lipid	330:334	arg1	role					320:323	an important role	307:323	an important role	307:323	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	3	28	theme	mice	627:630	arg1	cells					645:649	mice melanoma b16 cells	627:649	mice melanoma b16 cells	627:649	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	1	29	link	N-linked	175:182	arg1	base					170:173	a sphingoid base	158:173	a sphingoid base N-linked to a fatty acyl chain	158:204	Sphingolipids consist of a sphingoid base N-linked to a fatty acyl chain.
30359584	3	30	theme	quantitative	374:385	arg1	study					397:401	a quantitative lipidomic study	372:401	a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes)	372:688	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	31	dep	tissue	465:470	arg1	dog					526:528	dog	526:528	dog	526:528	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	31	dep	tissue	465:470	arg1	rat					518:520	rat	518:520	rat	518:520	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	32	theme	melanoma	632:639	arg1	cells					645:649	mice melanoma b16 cells	627:649	mice melanoma b16 cells	627:649	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	8	33	theme	divergent	1305:1313	arg1	tissue					1315:1320	the most divergent tissue	1296:1320	the most divergent tissue	1296:1320	Brain was the most divergent tissue, in which Cer and SM C18:0 were very abundant.
30359584	8	33	theme	divergent	1305:1313	arg1	Brain					1286:1290	Brain	1286:1290	Brain	1286:1290	Brain was the most divergent tissue, in which Cer and SM C18:0 were very abundant.
30359584	7	34	theme	all	1132:1134	arg1	samples					1136:1142	virtually all samples	1122:1142	virtually all samples	1122:1142	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	35	theme	main	1246:1249	arg1	C16:0					1279:1283	C16:0	1279:1283	C16:0	1279:1283	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	35	theme	main	1246:1249	arg1	species					1251:1257	the main species	1242:1257	the main species contained in SM	1242:1273	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	1	36	theme	fatty	189:193	arg1	chain					200:204	a fatty acyl chain	187:204	a fatty acyl chain	187:204	Sphingolipids consist of a sphingoid base N-linked to a fatty acyl chain.
30359584	5	37	from	sphingosine	988:998	arg1	cases					1039:1043	all cases	1035:1043	all cases	1035:1043	The sphingoid base was predominantly d18-1 sphingosine (2-amino-4-octadecene-1,3-diol) in all cases.
30359584	0	38	theme	physiological	105:117	arg1	implications					119:130	Biophysical and physiological implications	89:130	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.	0:131	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	6	39	theme	SM	1076:1077	arg1	different					1091:1099	different	1091:1099	different	1091:1099	The fatty acid composition of SM was clearly different from that of Cer.
30359584	6	39	theme	SM	1076:1077	arg1	composition					1061:1071	The fatty acid composition	1046:1071	The fatty acid composition of SM	1046:1077	The fatty acid composition of SM was clearly different from that of Cer.
30359584	2	40	theme	cells	273:277	arg1	sphingomyelins					219:232	sphingomyelins	219:232	sphingomyelins (SM)	219:237	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	2	40	theme	cells	273:277	arg1	components					249:258	major components	243:258	major components of mammalian cells	243:277	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	1	41	theme	acyl	195:198	arg1	chain					200:204	a fatty acyl chain	187:204	a fatty acyl chain	187:204	Sphingolipids consist of a sphingoid base N-linked to a fatty acyl chain.
30359584	7	42	theme	Cer	1162:1164	arg1	those					1179:1183	those	1179:1183	those	1179:1183	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	42	theme	Cer	1162:1164	arg1	species					1166:1172	the most abundant Cer species	1144:1172	the most abundant Cer species	1144:1172	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	5	43	theme	sphingoid	949:957	arg1	sphingosine					988:998	d18-1 sphingosine	982:998	d18-1 sphingosine (2-amino-4-octadecene-1,3-diol)	982:1030	The sphingoid base was predominantly d18-1 sphingosine (2-amino-4-octadecene-1,3-diol) in all cases.
30359584	5	43	theme	sphingoid	949:957	arg1	base					959:962	The sphingoid base	945:962	The sphingoid base	945:962	The sphingoid base was predominantly d18-1 sphingosine (2-amino-4-octadecene-1,3-diol) in all cases.
30359584	3	44	theme	mice	512:515	arg1	brain					480:484	brain	480:484	brain	480:484	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	44	theme	mice	512:515	arg1	serum					496:500	blood serum	490:500	blood serum	490:500	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	44	theme	mice	512:515	arg1	liver					473:477	liver	473:477	liver	473:477	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	44	theme	mice	512:515	arg1	tissues					448:454	different mammalian tissues	428:454	different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog)	428:529	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	44	theme	mice	512:515	arg1	tissue					465:470	adipose tissue	457:470	adipose tissue	457:470	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	45	theme	liquid	722:727	arg1	chromatography					729:742	an ultra-high performance liquid chromatography	696:742	an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	696:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	0	46	theme	sphingomyelins	19:32	arg1	acids					10:14	The fatty acids	0:14	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.	0:131	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	3	47	dep	hepatocytes	589:599	arg1	lymphocytes					677:687	primary CD4 + T lymphocytes	661:687	primary CD4 + T lymphocytes	661:687	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	7	48	contain	containing	1185:1194	arg1	those					1179:1183	those	1179:1183	those	1179:1183	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	48	contain	containing	1185:1194	arg1	species					1166:1172	the most abundant Cer species	1144:1172	the most abundant Cer species	1144:1172	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	48	contain	containing	1185:1194	arg2	C24:1					1206:1210	C24:1	1206:1210	C24:1	1206:1210	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	48	contain	containing	1185:1194	arg2	C24:0					1196:1200	C24:0	1196:1200	C24:0	1196:1200	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	3	49	theme	Cer	406:408	arg1	species					417:423	Cer and SM species	406:423	species	417:423	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	8	50	from	abundant	1359:1366	arg1	tissue					1315:1320	the most divergent tissue	1296:1320	the most divergent tissue	1296:1320	Brain was the most divergent tissue, in which Cer and SM C18:0 were very abundant.
30359584	8	50	from	abundant	1359:1366	arg1	Brain					1286:1290	Brain	1286:1290	Brain	1286:1290	Brain was the most divergent tissue, in which Cer and SM C18:0 were very abundant.
30359584	3	51	dep	origin	573:578	arg1	cells					645:649	mice melanoma b16 cells	627:649	mice melanoma b16 cells	627:649	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	51	dep	origin	573:578	arg1	cells					620:624	immortalized MDCK cells	602:624	immortalized MDCK cells	602:624	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	51	dep	origin	573:578	arg1	mice					656:659	mice	656:659	mice	656:659	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	51	dep	origin	573:578	arg1	hepatocytes					589:599	primary hepatocytes	581:599	primary hepatocytes	581:599	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	52	theme	human	505:509	arg1	mice					512:515	human, mice	505:515	mice	512:515	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	53	theme	different	428:436	arg1	brain					480:484	brain	480:484	brain	480:484	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	53	theme	different	428:436	arg1	serum					496:500	blood serum	490:500	blood serum	490:500	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	53	theme	different	428:436	arg1	liver					473:477	liver	473:477	liver	473:477	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	53	theme	different	428:436	arg1	tissues					448:454	different mammalian tissues	428:454	different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog)	428:529	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	53	theme	different	428:436	arg1	tissue					465:470	adipose tissue	457:470	adipose tissue	457:470	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	0	54	theme	ceramides	38:46	arg1	acids					10:14	The fatty acids	0:14	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.	0:131	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	3	55	theme	b16	641:643	arg1	cells					645:649	mice melanoma b16 cells	627:649	mice melanoma b16 cells	627:649	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	8	56	theme	SM	1340:1341	arg1	C18:0					1343:1347	SM C18:0	1340:1347	SM C18:0	1340:1347	Brain was the most divergent tissue, in which Cer and SM C18:0 were very abundant.
30359584	7	57	theme	abundant	1153:1160	arg1	those					1179:1183	those	1179:1183	those	1179:1183	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	57	theme	abundant	1153:1160	arg1	species					1166:1172	the most abundant Cer species	1144:1172	the most abundant Cer species	1144:1172	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	3	58	theme	mammalian	438:446	arg1	brain					480:484	brain	480:484	brain	480:484	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	58	theme	mammalian	438:446	arg1	serum					496:500	blood serum	490:500	blood serum	490:500	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	58	theme	mammalian	438:446	arg1	liver					473:477	liver	473:477	liver	473:477	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	58	theme	mammalian	438:446	arg1	tissues					448:454	different mammalian tissues	428:454	different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog)	428:529	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	58	theme	mammalian	438:446	arg1	tissue					465:470	adipose tissue	457:470	adipose tissue	457:470	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	59	theme	species	417:423	arg1	study					397:401	a quantitative lipidomic study	372:401	a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes)	372:688	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	6	60	from	that	1106:1109	arg1	different					1091:1099	different	1091:1099	different	1091:1099	The fatty acid composition of SM was clearly different from that of Cer.
30359584	6	60	from	that	1106:1109	arg1	composition					1061:1071	The fatty acid composition	1046:1071	The fatty acid composition of SM	1046:1077	The fatty acid composition of SM was clearly different from that of Cer.
30359584	3	61	theme	CD4 + T	669:675	arg1	lymphocytes					677:687	primary CD4 + T lymphocytes	661:687	primary CD4 + T lymphocytes	661:687	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	6	62	theme	acid	1056:1059	arg1	different					1091:1099	different	1091:1099	different	1091:1099	The fatty acid composition of SM was clearly different from that of Cer.
30359584	6	62	theme	acid	1056:1059	arg1	composition					1061:1071	The fatty acid composition	1046:1071	The fatty acid composition of SM	1046:1077	The fatty acid composition of SM was clearly different from that of Cer.
30359584	0	63	dep	acids	10:14	arg1	implications					119:130	Biophysical and physiological implications	89:130	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.	0:131	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	7	64	from	C24:0	1196:1200	arg1	chains					1228:1233	their N-acyl chains	1215:1233	their N-acyl chains	1215:1233	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	3	65	theme	performance	710:720	arg1	chromatography					729:742	an ultra-high performance liquid chromatography	696:742	an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	696:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	8	66	from	tissue	1315:1320	arg1	abundant					1359:1366	abundant	1359:1366	abundant	1359:1366	Brain was the most divergent tissue, in which Cer and SM C18:0 were very abundant.
30359584	3	67	theme	cell	546:549	arg1	cultures					551:558	cell cultures	546:558	cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes)	546:688	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	4	68	theme	good	929:932	arg1	agreement					934:942	good agreement	929:942	good agreement	929:942	The data have been compared with published, in general semi-quantitative, results from 20 other samples, with good agreement.
30359584	3	69	theme	adipose	457:463	arg1	tissues					448:454	different mammalian tissues	428:454	different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog)	428:529	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	69	theme	adipose	457:463	arg1	tissue					465:470	adipose tissue	457:470	adipose tissue	457:470	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	2	70	theme	second	336:341	arg1	messenger					343:351	a lipid second messenger	328:351	a lipid second messenger	328:351	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	2	70	theme	second	336:341	arg1	role					320:323	an important role	307:323	an important role	307:323	Among them, sphingomyelins (SM) are major components of mammalian cells, while ceramide (Cer) plays an important role as a lipid second messenger.
30359584	0	71	theme	mammalian	51:59	arg1	tissues					61:67	mammalian tissues	51:67	mammalian tissues	51:67	The fatty acids of sphingomyelins and ceramides in mammalian tissues and cultured cells: Biophysical and physiological implications.
30359584	4	72	theme	general	866:872	arg1	semi-quantitative					874:890	general semi-quantitative	866:890	general semi-quantitative	866:890	The data have been compared with published, in general semi-quantitative, results from 20 other samples, with good agreement.
30359584	7	73	theme	N-acyl	1221:1226	arg1	chains					1228:1233	their N-acyl chains	1215:1233	their N-acyl chains	1215:1233	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	7	74	from	C24:1	1206:1210	arg1	chains					1228:1233	their N-acyl chains	1215:1233	their N-acyl chains	1215:1233	In virtually all samples the most abundant Cer species were those containing C24:0 and C24:1 in their N-acyl chains, while the main species contained in SM was C16:0.
30359584	4	75	theme	other	909:913	arg1	samples					915:921	20 other samples	906:921	20 other samples	906:921	The data have been compared with published, in general semi-quantitative, results from 20 other samples, with good agreement.
30359584	3	76	theme	mass	770:773	arg1	platform					809:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform	755:816	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
30359584	3	77	theme	primary	661:667	arg1	lymphocytes					677:687	primary CD4 + T lymphocytes	661:687	primary CD4 + T lymphocytes	661:687	We have performed a quantitative lipidomic study of Cer and SM species in different mammalian tissues (adipose tissue, liver, brain and blood serum of human, mice, rat and dog), as well as in cell cultures of mammalian origin (primary hepatocytes, immortalized MDCK cells, mice melanoma b16 cells, and mice primary CD4 + T lymphocytes) using an ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC-ToF-MS)-based platform.
29760471	0	0	theme	protective	76:85	arg1	antigen					87:93	anthrax toxin protective antigen	62:93	anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device	62:146	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	3	1	gly	non-glycosylated	760:775	arg1	version					778:784	a non-glycosylated, version	758:784	version	778:784	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	2	dep	PANG	752:755	arg1	version					778:784	a non-glycosylated, version	758:784	version	778:784	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	1	3	theme	remedial	164:171	arg1	antibodies					190:199	various remedial human monoclonal antibodies	156:199	various remedial human monoclonal antibodies	156:199	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	3	4	theme	protective	928:937	arg1	PA					948:949	PA	948:949	PA	948:949	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	4	theme	protective	928:937	arg1	antigen					939:945	anthrax protective antigen	920:945	anthrax protective antigen (PA)	920:950	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	5	theme	N-linked	872:879	arg1	antibody					894:901	a fully human monoclonal N-linked glycosylated antibody	847:901	a fully human monoclonal N-linked glycosylated antibody	847:901	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	5	theme	N-linked	872:879	arg1	Valortim					837:844	Valortim	837:844	Valortim (a fully human monoclonal N-linked glycosylated antibody)	837:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	0	6	theme	toxin	70:74	arg1	antigen					87:93	anthrax toxin protective antigen	62:93	anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device	62:146	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	3	7	dep	B.	709:710	arg1	anthracis					712:720	anthracis	712:720	anthracis	712:720	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	8	theme	immobilised	697:707	arg1	antibodies					740:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	1	9	theme	human	173:177	arg1	antibodies					190:199	various remedial human monoclonal antibodies	156:199	various remedial human monoclonal antibodies	156:199	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	4	10	theme	Valortim-bound	1103:1116	arg1	column					1133:1138	a Valortim-bound haemoperfusion column	1101:1138	a Valortim-bound haemoperfusion column	1101:1138	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	3	11	theme	column	679:684	arg1	development					631:641	the development	627:641	the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody)	627:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	12	from	blood	1001:1005	arg1	removal					909:915	removal	909:915	removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood	909:1005	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	1	13	theme	anthrax	302:308	arg1	infection					310:318	anthrax infection	302:318	anthrax infection	302:318	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	0	14	theme	antigen	87:93	arg1	removal					51:57	The efficient removal	37:57	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.	0:147	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	4	15	theme	in	1229:1230	arg1	model					1253:1257	an in vivo PA rat infusion model	1226:1257	an in vivo PA rat infusion model	1226:1257	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	3	16	link	N-linked	872:879	arg1	antibody					894:901	a fully human monoclonal N-linked glycosylated antibody	847:901	a fully human monoclonal N-linked glycosylated antibody	847:901	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	16	link	N-linked	872:879	arg1	Valortim					837:844	Valortim	837:844	Valortim (a fully human monoclonal N-linked glycosylated antibody)	837:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	4	17	theme	anthrax	1196:1202	arg1	PA					1204:1205	anthrax PA	1196:1205	anthrax PA	1196:1205	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	3	18	theme	monoclonal	861:870	arg1	antibody					894:901	a fully human monoclonal N-linked glycosylated antibody	847:901	a fully human monoclonal N-linked glycosylated antibody	847:901	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	18	theme	monoclonal	861:870	arg1	Valortim					837:844	Valortim	837:844	Valortim (a fully human monoclonal N-linked glycosylated antibody)	837:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	0	19	theme	extracorporeal	104:117	arg1	device					141:146	an extracorporeal macroporous adsorbent device	101:146	an extracorporeal macroporous adsorbent device	101:146	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	2	20	theme	antibody-bound	563:576	arg1	device					604:609	an antibody-bound, adsorbent haemoperfusion device	560:609	an antibody-bound, adsorbent haemoperfusion device	560:609	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	1	21	theme	monoclonal	179:188	arg1	antibodies					190:199	various remedial human monoclonal antibodies	156:199	various remedial human monoclonal antibodies	156:199	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	2	22	dep	antibody-bound	563:576	arg1	adsorbent					579:587	adsorbent	579:587	adsorbent	579:587	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	5	23	theme	such	1335:1338	arg1	platforms					1367:1375	such alternative detoxification platforms	1335:1375	such alternative detoxification platforms	1335:1375	This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.
29760471	3	24	theme	antigen	939:945	arg1	removal					909:915	removal	909:915	removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood	909:1005	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	25	theme	monoclonal	812:821	arg1	antibody					823:830	a plant-produced human monoclonal antibody	789:830	a plant-produced human monoclonal antibody	789:830	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	4	26	theme	continuous	1047:1056	arg1	recirculation					1079:1091	continuous extracorporeal blood recirculation	1047:1091	continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column	1047:1138	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	3	27	theme	non-glycosylated	760:775	arg1	version					778:784	a non-glycosylated, version	758:784	version	778:784	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	5	28	theme	proof-of-concept	1279:1294	arg1	evidence					1296:1303	proof-of-concept evidence	1279:1303	proof-of-concept evidence to support the development of such alternative detoxification platforms	1279:1375	This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.
29760471	4	29	theme	infusion	1244:1251	arg1	model					1253:1257	an in vivo PA rat infusion model	1226:1257	an in vivo PA rat infusion model	1226:1257	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	4	30	theme	PA	1204:1205	arg1	concentration					1179:1191	the blood plasma concentration	1162:1191	the blood plasma concentration of anthrax PA over 2 hours	1162:1218	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	0	31	theme	Bioinspired	0:10	arg1	detoxification					12:25	Bioinspired detoxification	0:25	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.	0:147	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	3	32	theme	plant-produced	791:804	arg1	antibody					823:830	a plant-produced human monoclonal antibody	789:830	a plant-produced human monoclonal antibody	789:830	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	33	theme	frozen	965:970	arg1	plasma					978:983	freshly frozen human plasma	957:983	freshly frozen human plasma	957:983	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	2	34	theme	later	413:417	arg1	stages					419:424	the later stages	409:424	the later stages of infection	409:437	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	0	35	theme	blood	30:34	arg1	detoxification					12:25	Bioinspired detoxification	0:25	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.	0:147	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	3	36	theme	human	806:810	arg1	antibody					823:830	a plant-produced human monoclonal antibody	789:830	a plant-produced human monoclonal antibody	789:830	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	0	37	theme	adsorbent	131:139	arg1	device					141:146	an extracorporeal macroporous adsorbent device	101:146	an extracorporeal macroporous adsorbent device	101:146	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	3	38	theme	human	972:976	arg1	plasma					978:983	freshly frozen human plasma	957:983	freshly frozen human plasma	957:983	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	39	from	plasma	978:983	arg1	removal					909:915	removal	909:915	removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood	909:1005	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	4	40	theme	extracorporeal	1058:1071	arg1	recirculation					1079:1091	continuous extracorporeal blood recirculation	1047:1091	continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column	1047:1138	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	1	41	theme	optimal	324:330	arg1	route					373:377	an optimal and universally effective administration route	321:377	an optimal and universally effective administration route	321:377	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	0	42	theme	macroporous	119:129	arg1	device					141:146	an extracorporeal macroporous adsorbent device	101:146	an extracorporeal macroporous adsorbent device	101:146	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	3	43	gly	glycosylated	881:892	arg1	antibody					894:901	a fully human monoclonal N-linked glycosylated antibody	847:901	a fully human monoclonal N-linked glycosylated antibody	847:901	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	43	gly	glycosylated	881:892	arg1	Valortim					837:844	Valortim	837:844	Valortim (a fully human monoclonal N-linked glycosylated antibody)	837:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	4	44	dep	in	1229:1230	arg1	vivo					1232:1235	vivo	1232:1235	vivo	1232:1235	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	4	45	theme	blood	1166:1170	arg1	concentration					1179:1191	the blood plasma concentration	1162:1191	the blood plasma concentration of anthrax PA over 2 hours	1162:1218	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	2	46	theme	possible	508:515	arg1	route					517:521	one possible route	504:521	one possible route to improve outcome	504:540	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	5	47	theme	platforms	1367:1375	arg1	development					1320:1330	the development	1316:1330	the development of such alternative detoxification platforms	1316:1375	This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.
29760471	3	48	contain	containing	686:695	arg1	column					679:684	an adsorbent macroporous polymer column	646:684	an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody)	646:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	48	contain	containing	686:695	arg2	antibodies					740:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	48	contain	containing	686:695	arg2	PANG					752:755	PANG	752:755	PANG	752:755	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	48	contain	containing	686:695	arg2	antibody					894:901	a fully human monoclonal N-linked glycosylated antibody	847:901	a fully human monoclonal N-linked glycosylated antibody	847:901	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	48	contain	containing	686:695	arg2	Valortim					837:844	Valortim	837:844	Valortim (a fully human monoclonal N-linked glycosylated antibody)	837:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	4	49	theme	plasma	1172:1177	arg1	concentration					1179:1191	the blood plasma concentration	1162:1191	the blood plasma concentration of anthrax PA over 2 hours	1162:1218	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	2	50	theme	antibody	444:451	arg1	administration					453:466	antibody administration	444:466	antibody administration by injection	444:479	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	2	51	theme	infection	429:437	arg1	stages					419:424	the later stages	409:424	the later stages of infection	409:437	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	3	52	theme	glycosylated	881:892	arg1	antibody					894:901	a fully human monoclonal N-linked glycosylated antibody	847:901	a fully human monoclonal N-linked glycosylated antibody	847:901	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	52	theme	glycosylated	881:892	arg1	Valortim					837:844	Valortim	837:844	Valortim (a fully human monoclonal N-linked glycosylated antibody)	837:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	53	theme	macroporous	659:669	arg1	column					679:684	an adsorbent macroporous polymer column	646:684	an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody)	646:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	4	54	theme	blood	1073:1077	arg1	recirculation					1079:1091	continuous extracorporeal blood recirculation	1047:1091	continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column	1047:1138	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	3	55	theme	human	989:993	arg1	blood					1001:1005	human whole blood	989:1005	human whole blood	989:1005	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	1	56	theme	effective	348:356	arg1	route					373:377	an optimal and universally effective administration route	321:377	an optimal and universally effective administration route	321:377	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	3	57	theme	polymer	671:677	arg1	column					679:684	an adsorbent macroporous polymer column	646:684	an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody)	646:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	58	theme	whole	995:999	arg1	blood					1001:1005	human whole blood	989:1005	human whole blood	989:1005	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	0	59	theme	efficient	41:49	arg1	removal					51:57	The efficient removal	37:57	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.	0:147	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	1	60	theme	administration	358:371	arg1	route					373:377	an optimal and universally effective administration route	321:377	an optimal and universally effective administration route	321:377	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	2	61	theme	device	604:609	arg1	use					553:555	the use	549:555	the use of an antibody-bound, adsorbent haemoperfusion device	549:609	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	4	62	theme	rat	1240:1242	arg1	model					1253:1257	an in vivo PA rat infusion model	1226:1257	an in vivo PA rat infusion model	1226:1257	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	3	63	theme	antibody	823:830	arg1	version					778:784	a non-glycosylated, version	758:784	version	778:784	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	2	64	theme	haemoperfusion	589:602	arg1	device					604:609	an antibody-bound, adsorbent haemoperfusion device	560:609	an antibody-bound, adsorbent haemoperfusion device	560:609	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	3	65	theme	exotoxin-specific	722:738	arg1	antibodies					740:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	4	66	theme	PA	1237:1238	arg1	model					1253:1257	an in vivo PA rat infusion model	1226:1257	an in vivo PA rat infusion model	1226:1257	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	4	67	theme	haemoperfusion	1118:1131	arg1	column					1133:1138	a Valortim-bound haemoperfusion column	1101:1138	a Valortim-bound haemoperfusion column	1101:1138	In addition, we have demonstrated that continuous extracorporeal blood recirculation through a Valortim-bound haemoperfusion column significantly reduced the blood plasma concentration of anthrax PA over 2 hours using an in vivo PA rat infusion model.
29760471	2	68	from	use	553:555	arg1	stages					419:424	the later stages	409:424	the later stages of infection	409:437	In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device.
29760471	3	69	theme	adsorbent	649:657	arg1	column					679:684	an adsorbent macroporous polymer column	646:684	an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody)	646:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	5	70	theme	alternative	1340:1350	arg1	platforms					1367:1375	such alternative detoxification platforms	1335:1375	such alternative detoxification platforms	1335:1375	This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.
29760471	1	71	theme	life-threatening	246:261	arg1	complications					272:284	the potentially life-threatening systemic complications	230:284	the potentially life-threatening systemic complications associated with anthrax infection	230:318	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	0	72	theme	anthrax	62:68	arg1	antigen					87:93	anthrax toxin protective antigen	62:93	anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device	62:146	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	3	73	theme	B.	709:710	arg1	antibodies					740:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	immobilised B. anthracis exotoxin-specific antibodies	697:749	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	0	74	dep	detoxification	12:25	arg1	removal					51:57	The efficient removal	37:57	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.	0:147	Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.
29760471	5	75	theme	detoxification	1352:1365	arg1	platforms					1367:1375	such alternative detoxification platforms	1335:1375	such alternative detoxification platforms	1335:1375	This work provides proof-of-concept evidence to support the development of such alternative detoxification platforms.
29760471	1	76	theme	systemic	263:270	arg1	complications					272:284	the potentially life-threatening systemic complications	230:284	the potentially life-threatening systemic complications associated with anthrax infection	230:318	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	3	77	theme	human	855:859	arg1	antibody					894:901	a fully human monoclonal N-linked glycosylated antibody	847:901	a fully human monoclonal N-linked glycosylated antibody	847:901	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	77	theme	human	855:859	arg1	Valortim					837:844	Valortim	837:844	Valortim (a fully human monoclonal N-linked glycosylated antibody)	837:902	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	1	78	theme	various	156:162	arg1	antibodies					190:199	various remedial human monoclonal antibodies	156:199	various remedial human monoclonal antibodies	156:199	Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established.
29760471	3	79	theme	anthrax	920:926	arg1	PA					948:949	PA	948:949	PA	948:949	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
29760471	3	79	theme	anthrax	920:926	arg1	antigen					939:945	anthrax protective antigen	920:945	anthrax protective antigen (PA)	920:950	We report here the development of an adsorbent macroporous polymer column containing immobilised B. anthracis exotoxin-specific antibodies, PANG (a non-glycosylated, version of a plant-produced human monoclonal antibody) and Valortim (a fully human monoclonal N-linked glycosylated antibody), for removal of anthrax protective antigen (PA) from freshly frozen human plasma and human whole blood.
31341641	6	0	theme	maximum	872:878	arg1	likelihood					880:889	maximum likelihood	872:889	maximum likelihood	872:889	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	12	1	from	rates	1948:1952	arg1	gp120					1963:1967	HIV-1 gp120	1957:1967	HIV-1 gp120 across multiple subtypes and CRFs	1957:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	1	2	theme	glycoprotein	238:249	arg1	gp120					252:256	the surface envelope glycoprotein (gp120)	217:257	the surface envelope glycoprotein (gp120)	217:257	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	12	3	theme	first	1910:1914	arg1	measures					1930:1937	the first comprehensive measures	1906:1937	the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs	1906:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	1	4	theme	gp120	252:256	arg1	regions					198:204	the five variable regions	180:204	the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120)	180:257	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	1	4	theme	gp120	252:256	arg1	V1-V5					207:211	V1-V5	207:211	V1-V5	207:211	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	12	5	theme	novel	2019:2023	arg1	patterns					2040:2047	novel and unexpected patterns	2019:2047	novel and unexpected patterns for further research in the molecular evolution of HIV-1	2019:2104	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	4	6	theme	major	625:629	arg1	subtypes					631:638	five major subtypes	620:638	five major subtypes	620:638	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	11	7	theme	Indels	1705:1710	arg1	frequencies					1660:1670	higher frequencies	1653:1670	higher frequencies of G	1653:1675	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	11	7	theme	Indels	1705:1710	arg1	frequencies					1687:1697	lower frequencies	1681:1697	lower frequencies of T. Indels	1681:1710	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	6	8	from	tree	1014:1017	arg1	cherries					1020:1027	cherries	1020:1027	cherries	1020:1027	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	6	8	from	tree	1014:1017	arg1	pairs					987:991	closely related pairs	971:991	closely related pairs of sequences in each tree (cherries)	971:1028	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	2	9	from	change	335:340	arg1	regions					351:357	these regions	345:357	these regions	345:357	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	9	10	theme	HIV-1	1407:1411	arg1	B					1421:1421	HIV-1 subtype B	1407:1421	HIV-1 subtype B relative to the 01_AE reference	1407:1453	Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference.
31341641	4	11	theme	variable	596:603	arg1	regions					605:611	the gp120 variable regions	586:611	the gp120 variable regions	586:611	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	7	12	theme	indel	1110:1114	arg1	reconstructions					1116:1130	phylogenetically independent indel reconstructions	1081:1130	phylogenetically independent indel reconstructions	1081:1130	By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection.
31341641	5	13	theme	6,605	785:789	arg1	sequences					791:799	6,605 sequences	785:799	6,605 sequences	785:799	We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis.
31341641	7	14	from	scales	1154:1159	arg1	cherries					1164:1171	cherries	1164:1171	cherries	1164:1171	By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection.
31341641	11	15	from	selection	1824:1832	arg1	patterns					1851:1858	glycosylation patterns	1837:1858	glycosylation patterns within these regions	1837:1879	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	10	16	theme	longer	1525:1530	arg1	indels					1532:1537	significantly longer indels	1511:1537	significantly longer indels	1511:1537	We also found that V1, V2, and V4 tended to accumulate significantly longer indels.
31341641	11	17	theme	N-linked	1721:1728	arg1	sites					1744:1748	N-linked glycosylation sites	1721:1748	N-linked glycosylation sites	1721:1748	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	9	18	theme	01_AE	1439:1443	arg1	reference					1445:1453	the 01_AE reference	1435:1453	the 01_AE reference	1435:1453	Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference.
31341641	1	19	dep	transmission	84:95	arg1	fitness					97:103	fitness	97:103	fitness	97:103	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	0	20	theme	HIV-1	56:60	arg1	subtypes					70:77	the HIV-1 group M subtypes	52:77	the HIV-1 group M subtypes	52:77	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.
31341641	1	21	from	evolution	167:175	arg1	regions					198:204	the five variable regions	180:204	the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120)	180:257	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	1	21	from	evolution	167:175	arg1	V1-V5					207:211	V1-V5	207:211	V1-V5	207:211	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	11	22	from	sequence	1638:1645	arg1	distinct					1611:1618	distinct	1611:1618	distinct	1611:1618	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	11	22	from	sequence	1638:1645	arg1	composition					1585:1595	the nucleotide composition	1570:1595	the nucleotide composition of indels	1570:1605	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	4	23	theme	circulating	648:658	arg1	forms					672:676	two circulating recombinant forms	644:676	two circulating recombinant forms (CRFs) of HIV-1 group M	644:700	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	4	23	theme	circulating	648:658	arg1	CRFs					679:682	CRFs	679:682	CRFs	679:682	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	12	24	from	measures	1930:1937	arg1	gp120					1963:1967	HIV-1 gp120	1957:1967	HIV-1 gp120 across multiple subtypes and CRFs	1957:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	11	25	theme	lower	1681:1685	arg1	frequencies					1687:1697	lower frequencies	1681:1697	lower frequencies of T. Indels	1681:1710	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	0	26	theme	M	68:68	arg1	subtypes					70:77	the HIV-1 group M subtypes	52:77	the HIV-1 group M subtypes	52:77	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.
31341641	6	27	theme	indels	956:961	arg1	distribution					940:951	the observed distribution	927:951	the observed distribution of indels between closely related pairs of sequences in each tree (cherries)	927:1028	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	11	28	theme	G	1675:1675	arg1	frequencies					1660:1670	higher frequencies	1653:1670	higher frequencies of G	1653:1675	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	11	28	theme	G	1675:1675	arg1	frequencies					1687:1697	lower frequencies	1681:1697	lower frequencies of T. Indels	1681:1710	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	1	29	theme	HIV-1	125:129	arg1	transmission					84:95	The transmission fitness and pathogenesis	80:120	transmission	84:95	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	1	29	theme	HIV-1	125:129	arg1	pathogenesis					109:120	pathogenesis	109:120	pathogenesis	109:120	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	3	30	theme	indels	397:402	arg1	composition					382:392	composition	382:392	composition	382:392	However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences.
31341641	3	30	theme	indels	397:402	arg1	rate					373:376	rate	373:376	rate	373:376	However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences.
31341641	7	31	theme	shorter	1141:1147	arg1	scales					1154:1159	the shorter time scales	1137:1159	the shorter time scales in cherries	1137:1171	By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection.
31341641	1	32	gly	glycoprotein	238:249	arg1	glycoprotein					238:249	the surface envelope glycoprotein (gp120)	217:257	the surface envelope glycoprotein (gp120)	217:257	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	3	33	dep	rate	373:376	arg1	the					369:371	the	369:371	the	369:371	However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences.
31341641	0	34	theme	Phylogenetic	0:11	arg1	measures					13:20	Phylogenetic measures	0:20	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes	0:77	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.
31341641	4	35	theme	group	694:698	arg1	M					700:700	HIV-1 group M	688:700	HIV-1 group M	688:700	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	7	36	from	cherries	1046:1053	arg1	tree					1063:1066	each tree	1058:1066	each tree	1058:1066	By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection.
31341641	11	37	theme	positive	1815:1822	arg1	selection					1824:1832	positive selection	1815:1832	positive selection on glycosylation patterns within these regions	1815:1879	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	7	38	theme	independent	1098:1108	arg1	reconstructions					1116:1130	phylogenetically independent indel reconstructions	1081:1130	phylogenetically independent indel reconstructions	1081:1130	By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection.
31341641	0	39	theme	rate	31:34	arg1	variation					36:44	indel rate variation	25:44	indel rate variation among the HIV-1 group M subtypes	25:77	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.
31341641	2	40	from	regions	351:357	arg1	Insertions					260:269	Insertions	260:269	Insertions	260:269	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	2	40	from	regions	351:357	arg1	source					312:317	a significant source	298:317	a significant source of evolutionary change in these regions	298:357	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	2	40	from	regions	351:357	arg1	deletions					275:283	deletions	275:283	deletions	275:283	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	6	41	theme	sequences	996:1004	arg1	cherries					1020:1027	cherries	1020:1027	cherries	1020:1027	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	6	41	theme	sequences	996:1004	arg1	pairs					987:991	closely related pairs	971:991	closely related pairs of sequences in each tree (cherries)	971:1028	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	11	42	gly	glycosylation	1730:1742	arg2	sites					1744:1748	N-linked glycosylation sites	1721:1748	N-linked glycosylation sites	1721:1748	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	3	43	theme	large-scale	442:452	arg1	analysis					466:473	a large-scale comparative analysis	440:473	a large-scale comparative analysis of HIV-1 sequences	440:492	However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences.
31341641	5	44	theme	HIV-1	738:742	arg1	gp120					744:748	HIV-1 gp120	738:748	26,000 published HIV-1 gp120 sequences	721:758	We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis.
31341641	12	45	from	gp120	1963:1967	arg1	measures					1930:1937	the first comprehensive measures	1906:1937	the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs	1906:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	11	46	theme	flanking	1629:1636	arg1	sequence					1638:1645	the flanking sequence	1625:1645	the flanking sequence	1625:1645	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	12	47	theme	molecular	2077:2085	arg1	evolution					2087:2095	the molecular evolution	2073:2095	the molecular evolution of HIV-1	2073:2104	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	3	48	theme	HIV-1	478:482	arg1	sequences					484:492	HIV-1 sequences	478:492	HIV-1 sequences	478:492	However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences.
31341641	7	49	theme	purifying	1197:1205	arg1	selection					1207:1215	purifying selection	1197:1215	purifying selection	1197:1215	By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection.
31341641	4	50	theme	indel	570:574	arg1	rates					576:580	indel rates	570:580	indel rates for the gp120 variable regions across five major subtypes	570:638	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	2	51	theme	evolutionary	322:333	arg1	change					335:340	evolutionary change	322:340	evolutionary change in these regions	322:357	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	1	52	theme	envelope	229:236	arg1	gp120					252:256	the surface envelope glycoprotein (gp120)	217:257	the surface envelope glycoprotein (gp120)	217:257	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	12	53	theme	rates	1948:1952	arg1	measures					1930:1937	the first comprehensive measures	1906:1937	the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs	1906:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	12	54	from	research	2061:2068	arg1	evolution					2087:2095	the molecular evolution	2073:2095	the molecular evolution of HIV-1	2073:2104	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	6	55	theme	time-scaled	845:855	arg1	phylogenies					857:867	time-scaled phylogenies	845:867	time-scaled phylogenies	845:867	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	2	56	from	source	312:317	arg1	regions					351:357	these regions	345:357	these regions	345:357	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	12	57	theme	multiple	1976:1983	arg1	subtypes					1985:1992	multiple subtypes	1976:1992	multiple subtypes	1976:1992	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	4	58	theme	phylogenetic	538:549	arg1	method					551:556	a phylogenetic method	536:556	a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M	536:700	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	12	59	theme	further	2053:2059	arg1	research					2061:2068	further research	2053:2068	further research in the molecular evolution of HIV-1	2053:2104	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	12	60	theme	comprehensive	1916:1928	arg1	measures					1930:1937	the first comprehensive measures	1906:1937	the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs	1906:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	12	61	theme	unexpected	2029:2038	arg1	patterns					2040:2047	novel and unexpected patterns	2019:2047	novel and unexpected patterns for further research in the molecular evolution of HIV-1	2019:2104	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	11	62	theme	nucleotide	1574:1583	arg1	distinct					1611:1618	distinct	1611:1618	distinct	1611:1618	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	11	62	theme	nucleotide	1574:1583	arg1	composition					1585:1595	the nucleotide composition	1570:1595	the nucleotide composition of indels	1570:1605	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	6	63	from	sequences	996:1004	arg1	tree					1014:1017	each tree	1009:1017	each tree	1009:1017	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	5	64	theme	phylogenetic	805:816	arg1	analysis					818:825	phylogenetic analysis	805:825	phylogenetic analysis	805:825	We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis.
31341641	6	65	theme	observed	931:938	arg1	distribution					940:951	the observed distribution	927:951	the observed distribution of indels between closely related pairs of sequences in each tree (cherries)	927:1028	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	1	66	theme	variable	189:196	arg1	regions					198:204	the five variable regions	180:204	the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120)	180:257	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	1	66	theme	variable	189:196	arg1	V1-V5					207:211	V1-V5	207:211	V1-V5	207:211	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
31341641	2	67	theme	significant	300:310	arg1	Insertions					260:269	Insertions	260:269	Insertions	260:269	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	2	67	theme	significant	300:310	arg1	source					312:317	a significant source	298:317	a significant source of evolutionary change in these regions	298:357	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	2	67	theme	significant	300:310	arg1	deletions					275:283	deletions	275:283	deletions	275:283	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	9	68	theme	subtype	1413:1419	arg1	B					1421:1421	HIV-1 subtype B	1407:1421	HIV-1 subtype B relative to the 01_AE reference	1407:1453	Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference.
31341641	6	69	theme	binomial-Poisson	901:916	arg1	model					918:922	a binomial-Poisson model	899:922	a binomial-Poisson model	899:922	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	11	70	link	N-linked	1721:1728	arg1	sites					1744:1748	N-linked glycosylation sites	1721:1748	N-linked glycosylation sites	1721:1748	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	4	71	theme	gp120	590:594	arg1	regions					605:611	the gp120 variable regions	586:611	the gp120 variable regions	586:611	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	7	72	theme	time	1149:1152	arg1	scales					1154:1159	the shorter time scales	1137:1159	the shorter time scales in cherries	1137:1171	By focusing on cherries in each tree, we obtained phylogenetically independent indel reconstructions, and the shorter time scales in cherries reduced the bias due to purifying selection.
31341641	9	73	theme	relative	1423:1430	arg1	B					1421:1421	HIV-1 subtype B	1407:1421	HIV-1 subtype B relative to the 01_AE reference	1407:1453	Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference.
31341641	4	74	theme	recombinant	660:670	arg1	forms					672:676	two circulating recombinant forms	644:676	two circulating recombinant forms (CRFs) of HIV-1 group M	644:700	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	4	74	theme	recombinant	660:670	arg1	CRFs					679:682	CRFs	679:682	CRFs	679:682	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	11	75	theme	glycosylation	1730:1742	arg1	sites					1744:1748	N-linked glycosylation sites	1721:1748	N-linked glycosylation sites	1721:1748	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	11	76	with	consistent	1799:1808	arg1	selection					1824:1832	positive selection	1815:1832	positive selection on glycosylation patterns within these regions	1815:1879	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	0	77	theme	group	62:66	arg1	subtypes					70:77	the HIV-1 group M subtypes	52:77	the HIV-1 group M subtypes	52:77	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.
31341641	6	78	theme	related	979:985	arg1	cherries					1020:1027	cherries	1020:1027	cherries	1020:1027	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	6	78	theme	related	979:985	arg1	pairs					987:991	closely related pairs	971:991	closely related pairs of sequences in each tree (cherries)	971:1028	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	12	79	theme	HIV-1	1957:1961	arg1	gp120					1963:1967	HIV-1 gp120	1957:1967	HIV-1 gp120 across multiple subtypes and CRFs	1957:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	11	80	theme	higher	1653:1658	arg1	frequencies					1660:1670	higher frequencies	1653:1670	higher frequencies of G	1653:1675	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	4	81	from	method	551:556	arg1	results					523:529	results	523:529	results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M	523:700	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	6	82	from	pairs	987:991	arg1	tree					1014:1017	each tree	1009:1017	each tree	1009:1017	We reconstructed time-scaled phylogenies by maximum likelihood and fit a binomial-Poisson model to the observed distribution of indels between closely related pairs of sequences in each tree (cherries).
31341641	4	83	theme	M	700:700	arg1	forms					672:676	two circulating recombinant forms	644:676	two circulating recombinant forms (CRFs) of HIV-1 group M	644:700	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	4	83	theme	M	700:700	arg1	CRFs					679:682	CRFs	679:682	CRFs	679:682	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	4	83	theme	M	700:700	arg1	rates					576:580	indel rates	570:580	indel rates for the gp120 variable regions across five major subtypes	570:638	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	5	84	theme	gp120	744:748	arg1	sequences					750:758	26,000 published HIV-1 gp120 sequences	721:758	26,000 published HIV-1 gp120 sequences	721:758	We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis.
31341641	11	85	theme	T.	1702:1703	arg1	Indels					1705:1710	T. Indels	1702:1710	T. Indels	1702:1710	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	0	86	theme	indel	25:29	arg1	variation					36:44	indel rate variation	25:44	indel rate variation among the HIV-1 group M subtypes	25:77	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.
31341641	4	87	theme	HIV-1	688:692	arg1	M					700:700	HIV-1 group M	688:700	HIV-1 group M	688:700	Here, we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M.
31341641	11	88	theme	glycosylation	1837:1849	arg1	patterns					1851:1858	glycosylation patterns	1837:1858	glycosylation patterns within these regions	1837:1879	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	0	89	theme	variation	36:44	arg1	measures					13:20	Phylogenetic measures	0:20	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes	0:77	Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes.
31341641	11	90	theme	indels	1600:1605	arg1	distinct					1611:1618	distinct	1611:1618	distinct	1611:1618	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	11	90	theme	indels	1600:1605	arg1	composition					1585:1595	the nucleotide composition	1570:1595	the nucleotide composition of indels	1570:1605	Furthermore, we observed that the nucleotide composition of indels was distinct from the flanking sequence, with higher frequencies of G and lower frequencies of T. Indels affected N-linked glycosylation sites more often in V1 and V2 than expected by chance, consistent with positive selection on glycosylation patterns within these regions.
31341641	5	91	theme	published	728:736	arg1	sequences					750:758	26,000 published HIV-1 gp120 sequences	721:758	26,000 published HIV-1 gp120 sequences	721:758	We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis.
31341641	9	92	theme	Indel	1325:1329	arg1	rates					1331:1335	Indel rates	1325:1335	Indel rates	1325:1335	Indel rates were significantly lower in V3 relative to V1, and were also lower in HIV-1 subtype B relative to the 01_AE reference.
31341641	12	93	theme	HIV-1	2100:2104	arg1	evolution					2087:2095	the molecular evolution	2073:2095	the molecular evolution of HIV-1	2073:2104	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	3	94	theme	comparative	454:464	arg1	analysis					466:473	a large-scale comparative analysis	440:473	a large-scale comparative analysis of HIV-1 sequences	440:492	However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences.
31341641	2	95	theme	change	335:340	arg1	Insertions					260:269	Insertions	260:269	Insertions	260:269	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	2	95	theme	change	335:340	arg1	source					312:317	a significant source	298:317	a significant source of evolutionary change in these regions	298:357	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	2	95	theme	change	335:340	arg1	deletions					275:283	deletions	275:283	deletions	275:283	Insertions and deletions (indels) are a significant source of evolutionary change in these regions.
31341641	8	96	theme	variable	1294:1301	arg1	regions					1303:1309	variable regions	1294:1309	variable regions	1294:1309	Rate estimates ranged from to indels/nt/year and varied significantly among variable regions and subtypes.
31341641	12	97	theme	indel	1942:1946	arg1	rates					1948:1952	indel rates	1942:1952	indel rates in HIV-1 gp120 across multiple subtypes and CRFs	1942:2001	These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.
31341641	8	98	theme	Rate	1218:1221	arg1	estimates					1223:1231	Rate estimates	1218:1231	Rate estimates	1218:1231	Rate estimates ranged from to indels/nt/year and varied significantly among variable regions and subtypes.
31341641	3	99	theme	sequences	484:492	arg1	analysis					466:473	a large-scale comparative analysis	440:473	a large-scale comparative analysis of HIV-1 sequences	440:492	However, the rate and composition of indels has not yet been quantified through a large-scale comparative analysis of HIV-1 sequences.
31341641	1	100	theme	surface	221:227	arg1	gp120					252:256	the surface envelope glycoprotein (gp120)	217:257	the surface envelope glycoprotein (gp120)	217:257	The transmission fitness and pathogenesis of HIV-1 is disproportionately influenced by evolution in the five variable regions (V1-V5) of the surface envelope glycoprotein (gp120).
30633504	3	0	theme	pastoris	431:438	arg1	strain					404:409	an engineered strain	390:409	an engineered strain of the yeast Pichia pastoris	390:438	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	6	1	gly	N-Glycosylation	982:996	arg2	Asn34					1001:1005	Asn34	1001:1005	Asn34	1001:1005	N-Glycosylation at Asn34 generates the most active and stable glycoforms, in accord with its sequon being highly conserved among vertebrate species.
30633504	3	2	theme	RNase	586:590	arg1	form					572:575	the authentic triglycosylated form	542:575	the authentic triglycosylated form of human RNase 1	542:592	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	7	3	from	insight	1154:1160	arg1	role					1180:1183	the biological role	1165:1183	the biological role of the N-glycosylation of a human secretory enzyme	1165:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	6	4	from	Asn34	1001:1005	arg1	N-Glycosylation					982:996	N-Glycosylation	982:996	N-Glycosylation at Asn34	982:1005	N-Glycosylation at Asn34 generates the most active and stable glycoforms, in accord with its sequon being highly conserved among vertebrate species.
30633504	7	5	theme	biological	1169:1178	arg1	role					1180:1183	the biological role	1165:1183	the biological role of the N-glycosylation of a human secretory enzyme	1165:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	6	6	theme	active	1026:1031	arg1	glycoforms					1044:1053	the most active and stable glycoforms	1017:1053	the most active and stable glycoforms	1017:1053	N-Glycosylation at Asn34 generates the most active and stable glycoforms, in accord with its sequon being highly conserved among vertebrate species.
30633504	6	7	dep	glycoforms	1044:1053	arg1	accord					1059:1064	accord	1059:1064	accord with its sequon being highly conserved among vertebrate species	1059:1128	N-Glycosylation at Asn34 generates the most active and stable glycoforms, in accord with its sequon being highly conserved among vertebrate species.
30633504	6	8	theme	vertebrate	1111:1120	arg1	species					1122:1128	vertebrate species	1111:1128	vertebrate species	1111:1128	N-Glycosylation at Asn34 generates the most active and stable glycoforms, in accord with its sequon being highly conserved among vertebrate species.
30633504	4	9	theme	RNase	805:809	arg1	forms					796:800	the three diglycosylated and three monoglycosylated forms	744:800	the three diglycosylated and three monoglycosylated forms of RNase 1	744:811	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	4	10	theme	strategic	685:693	arg1	substitutions					719:731	strategic asparagine-to-glutamine substitutions	685:731	strategic asparagine-to-glutamine substitutions	685:731	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	5	11	theme	RNase	851:855	arg1	N-glycosylation					832:846	the N-glycosylation	828:846	the N-glycosylation of RNase 1 at any position	828:873	We found that the N-glycosylation of RNase 1 at any position attenuates its catalytic activity but enhances both its thermostability and its resistance to proteolysis.
30633504	4	12	theme	glutamine	600:608	arg1	substrate					627:635	a substrate	625:635	a substrate for cellular oligosaccharyltransferase	625:674	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	4	12	theme	glutamine	600:608	arg1	residue					610:616	a glutamine residue	598:616	a glutamine residue	598:616	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	2	13	theme	RNase	361:365	arg1	structure					335:343	structure	335:343	structure	335:343	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	2	13	theme	RNase	361:365	arg1	function					349:356	function	349:356	function	349:356	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	5	14	theme	catalytic	890:898	arg1	activity					900:907	its catalytic activity	886:907	its catalytic activity	886:907	We found that the N-glycosylation of RNase 1 at any position attenuates its catalytic activity but enhances both its thermostability and its resistance to proteolysis.
30633504	1	15	theme	archetypal	142:151	arg1	RNase					169:173	the archetypal enzyme RNase A. RNase 1	138:175	the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	138:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	4	16	theme	diglycosylated	754:767	arg1	forms					796:800	the three diglycosylated and three monoglycosylated forms	744:800	the three diglycosylated and three monoglycosylated forms of RNase 1	744:811	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	2	17	from	effect	302:307	arg1	structure					335:343	structure	335:343	structure	335:343	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	2	17	from	effect	302:307	arg1	function					349:356	function	349:356	function	349:356	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	1	18	theme	enzyme	153:158	arg1	RNase					169:173	the archetypal enzyme RNase A. RNase 1	138:175	the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	138:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	7	19	theme	new	1150:1152	arg1	insight					1154:1160	new insight	1150:1160	new insight on the biological role of the N-glycosylation of a human secretory enzyme	1150:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	4	20	theme	monoglycosylated	779:794	arg1	forms					796:800	the three diglycosylated and three monoglycosylated forms	744:800	the three diglycosylated and three monoglycosylated forms of RNase 1	744:811	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	7	21	theme	N-glycosylation	1192:1206	arg1	role					1180:1183	the biological role	1165:1183	the biological role of the N-glycosylation of a human secretory enzyme	1165:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	1	22	theme	RNase	160:164	arg1	RNase					169:173	the archetypal enzyme RNase A. RNase 1	138:175	the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	138:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	3	23	theme	side	493:496	arg1	chain					498:502	the side chain	489:502	the side chain of Asn34, Asn76, and Asn88	489:529	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	1	24	theme	A.	166:167	arg1	RNase					169:173	the archetypal enzyme RNase A. RNase 1	138:175	the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	138:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	0	25	theme	Endogenous	20:29	arg1	N-Glycosylation					31:45	the Endogenous N-Glycosylation	16:45	the Endogenous N-Glycosylation of Human Ribonuclease 1	16:69	Consequences of the Endogenous N-Glycosylation of Human Ribonuclease 1.
30633504	3	26	theme	Asn76	514:518	arg1	chain					498:502	the side chain	489:502	the side chain of Asn34, Asn76, and Asn88	489:529	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	5	27	gly	N-glycosylation	832:846	arg1	position					866:873	any position	862:873	any position	862:873	We found that the N-glycosylation of RNase 1 at any position attenuates its catalytic activity but enhances both its thermostability and its resistance to proteolysis.
30633504	5	27	gly	N-glycosylation	832:846	arg2	position					866:873	any position	862:873	any position	862:873	We found that the N-glycosylation of RNase 1 at any position attenuates its catalytic activity but enhances both its thermostability and its resistance to proteolysis.
30633504	5	27	gly	N-glycosylation	832:846	arg1	RNase					851:855	RNase 1	851:857	RNase 1	851:857	We found that the N-glycosylation of RNase 1 at any position attenuates its catalytic activity but enhances both its thermostability and its resistance to proteolysis.
30633504	1	28	link	N-linked	198:205	arg1	glycosylation					207:219	N-linked glycosylation	198:219	N-linked glycosylation	198:219	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	29	theme	RNase	169:173	arg1	Ribonuclease					72:83	Ribonuclease 1	72:85	Ribonuclease 1 (RNase 1)	72:95	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	29	theme	RNase	169:173	arg1	homologue					125:133	the most prevalent human homologue	100:133	the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	100:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	3	30	theme	engineered	393:402	arg1	strain					404:409	an engineered strain	390:409	an engineered strain of the yeast Pichia pastoris	390:438	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	2	31	gly	N-glycosylation	312:326	arg1	RNase					361:365	RNase 1	361:367	RNase 1	361:367	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	4	32	used	used	680:683	arg2	we					677:678	we	677:678	we	677:678	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	1	33	theme	human	119:123	arg1	Ribonuclease					72:83	Ribonuclease 1	72:85	Ribonuclease 1 (RNase 1)	72:95	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	33	theme	human	119:123	arg1	homologue					125:133	the most prevalent human homologue	100:133	the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	100:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	7	34	theme	secretory	1219:1227	arg1	enzyme					1229:1234	a human secretory enzyme	1211:1234	a human secretory enzyme	1211:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	3	35	theme	authentic	546:554	arg1	form					572:575	the authentic triglycosylated form	542:575	the authentic triglycosylated form of human RNase 1	542:592	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	3	36	theme	Asn34	507:511	arg1	chain					498:502	the side chain	489:502	the side chain of Asn34, Asn76, and Asn88	489:529	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	7	37	theme	human	1213:1217	arg1	enzyme					1229:1234	a human secretory enzyme	1211:1234	a human secretory enzyme	1211:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	0	38	theme	N-Glycosylation	31:45	arg1	Consequences					0:11	Consequences	0:11	Consequences of the Endogenous N-Glycosylation of Human Ribonuclease 1	0:69	Consequences of the Endogenous N-Glycosylation of Human Ribonuclease 1.
30633504	4	39	theme	cellular	641:648	arg1	oligosaccharyltransferase					650:674	cellular oligosaccharyltransferase	641:674	cellular oligosaccharyltransferase	641:674	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	4	40	gly	monoglycosylated	779:794	arg1	RNase					805:809	RNase 1	805:811	RNase 1	805:811	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	4	40	gly	monoglycosylated	779:794	arg1	forms					796:800	the three diglycosylated and three monoglycosylated forms	744:800	the three diglycosylated and three monoglycosylated forms of RNase 1	744:811	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	0	41	theme	Ribonuclease	56:67	arg1	N-Glycosylation					31:45	the Endogenous N-Glycosylation	16:45	the Endogenous N-Glycosylation of Human Ribonuclease 1	16:69	Consequences of the Endogenous N-Glycosylation of Human Ribonuclease 1.
30633504	6	42	theme	stable	1037:1042	arg1	glycoforms					1044:1053	the most active and stable glycoforms	1017:1053	the most active and stable glycoforms	1017:1053	N-Glycosylation at Asn34 generates the most active and stable glycoforms, in accord with its sequon being highly conserved among vertebrate species.
30633504	3	43	theme	yeast	418:422	arg1	pastoris					431:438	the yeast Pichia pastoris	414:438	the yeast Pichia pastoris	414:438	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	0	44	theme	Human	50:54	arg1	Ribonuclease					56:67	Human Ribonuclease 1	50:69	Human Ribonuclease 1	50:69	Consequences of the Endogenous N-Glycosylation of Human Ribonuclease 1.
30633504	3	45	theme	Pichia	424:429	arg1	pastoris					431:438	the yeast Pichia pastoris	414:438	the yeast Pichia pastoris	414:438	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	4	46	theme	asparagine-to-glutamine	695:717	arg1	substitutions					719:731	strategic asparagine-to-glutamine substitutions	685:731	strategic asparagine-to-glutamine substitutions	685:731	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	7	47	gly	N-glycosylation	1192:1206	arg1	enzyme					1229:1234	a human secretory enzyme	1211:1234	a human secretory enzyme	1211:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	3	48	theme	human	580:584	arg1	RNase					586:590	human RNase 1	580:592	human RNase 1	580:592	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	0	49	gly	N-Glycosylation	31:45	arg1	Ribonuclease					56:67	Human Ribonuclease 1	50:69	Human Ribonuclease 1	50:69	Consequences of the Endogenous N-Glycosylation of Human Ribonuclease 1.
30633504	5	50	from	position	866:873	arg1	N-glycosylation					832:846	the N-glycosylation	828:846	the N-glycosylation of RNase 1 at any position	828:873	We found that the N-glycosylation of RNase 1 at any position attenuates its catalytic activity but enhances both its thermostability and its resistance to proteolysis.
30633504	3	51	theme	triglycosylated	556:570	arg1	form					572:575	the authentic triglycosylated form	542:575	the authentic triglycosylated form of human RNase 1	542:592	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	3	52	theme	Asn88	525:529	arg1	chain					498:502	the side chain	489:502	the side chain of Asn34, Asn76, and Asn88	489:529	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	1	53	theme	prevalent	109:117	arg1	Ribonuclease					72:83	Ribonuclease 1	72:85	Ribonuclease 1 (RNase 1)	72:95	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	53	theme	prevalent	109:117	arg1	homologue					125:133	the most prevalent human homologue	100:133	the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	100:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	54	theme	N-linked	198:205	arg1	glycosylation					207:219	N-linked glycosylation	198:219	N-linked glycosylation	198:219	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	4	55	gly	diglycosylated	754:767	arg1	RNase					805:809	RNase 1	805:811	RNase 1	805:811	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	4	55	gly	diglycosylated	754:767	arg1	forms					796:800	the three diglycosylated and three monoglycosylated forms	744:800	the three diglycosylated and three monoglycosylated forms of RNase 1	744:811	As a glutamine residue is not a substrate for cellular oligosaccharyltransferase, we used strategic asparagine-to-glutamine substitutions to produce the three diglycosylated and three monoglycosylated forms of RNase 1.
30633504	1	56	dep	RNase	169:173	arg1	contains					177:184	contains	177:184	contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88	177:246	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	56	dep	RNase	169:173	arg1	N-glycosylated					255:268	N-glycosylated	255:268	N-glycosylated	255:268	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	57	gly	N-glycosylated	255:268	arg2	sites					283:287	all three sites	273:287	all three sites	273:287	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	1	57	gly	N-glycosylated	255:268	arg1	RNase					169:173	the archetypal enzyme RNase A. RNase 1	138:175	the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo	138:295	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	2	58	theme	N-glycosylation	312:326	arg1	effect					302:307	The effect	298:307	The effect of N-glycosylation on the structure and function of RNase 1	298:367	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	2	58	theme	N-glycosylation	312:326	arg1	unknown					372:378	unknown	372:378	unknown	372:378	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	7	59	theme	enzyme	1229:1234	arg1	N-glycosylation					1192:1206	the N-glycosylation	1188:1206	the N-glycosylation of a human secretory enzyme	1188:1234	These data provide new insight on the biological role of the N-glycosylation of a human secretory enzyme.
30633504	1	60	from	sites	283:287	arg1	N-glycosylated					255:268	N-glycosylated	255:268	N-glycosylated	255:268	Ribonuclease 1 (RNase 1) is the most prevalent human homologue of the archetypal enzyme RNase A. RNase 1 contains sequons for N-linked glycosylation at Asn34, Asn76, and Asn88 and is N-glycosylated at all three sites in vivo.
30633504	2	61	dep	structure	335:343	arg1	the					331:333	the	331:333	the	331:333	The effect of N-glycosylation on the structure and function of RNase 1 is unknown.
30633504	3	62	gly	triglycosylated	556:570	arg1	form					572:575	the authentic triglycosylated form	542:575	the authentic triglycosylated form of human RNase 1	542:592	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
30633504	3	62	gly	triglycosylated	556:570	arg1	RNase					586:590	human RNase 1	580:592	human RNase 1	580:592	By using an engineered strain of the yeast Pichia pastoris, we installed a heptasaccharide (Man5GlcNAc2) on the side chain of Asn34, Asn76, and Asn88 to produce the authentic triglycosylated form of human RNase 1.
31373799	7	0	theme	specificities	1315:1327	arg1	investigation					1278:1290	A detailed investigation	1267:1290	A detailed investigation of enzyme kinetics and specificities	1267:1327	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	5	1	theme	enzyme-substrate	935:950	arg1	pairs					952:956	enzyme-substrate pairs	935:956	enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs	935:1063	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	6	2	theme	peptide	1183:1189	arg1	substrates					1191:1200	nonglycosylated peptide substrates	1167:1200	nonglycosylated peptide substrates	1167:1200	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	3	3	theme	substrate	552:560	arg1	specificity					562:572	their substrate specificity	546:572	their substrate specificity	546:572	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	5	4	theme	enzyme-substrate	1042:1057	arg1	pairs					1059:1063	native enzyme-substrate pairs	1035:1063	native enzyme-substrate pairs	1035:1063	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	3	5	theme	disease	401:407	arg1	relevance					409:417	proven disease relevance	394:417	proven disease relevance	394:417	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	2	6	theme	glycosylation	307:319	arg1	form					299:302	this form	294:302	this form of glycosylation	294:319	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	4	7	theme	bump-hole	631:639	arg1	system					660:665	a "bump-hole" chemical reporter system	628:665	a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro	628:705	Here, we develop a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro.
31373799	7	8	theme	enzyme	1295:1300	arg1	kinetics					1302:1309	enzyme kinetics	1295:1309	enzyme kinetics	1295:1309	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	6	9	theme	peptide	1248:1254	arg1	substrate					1256:1264	a preglycosylated peptide substrate	1230:1264	a preglycosylated peptide substrate	1230:1264	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	5	10	theme	Individual	708:717	arg1	GalNAc-Ts					719:727	Individual GalNAc-Ts	708:727	Individual GalNAc-Ts	708:727	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	1	11	theme	α-N-acetylgalactosamine	84:106	arg1	glycans					119:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans	75:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans	75:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome.
31373799	6	12	theme	nonglycosylated	1167:1181	arg1	substrates					1191:1200	nonglycosylated peptide substrates	1167:1200	nonglycosylated peptide substrates	1167:1200	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	5	13	theme	native	1035:1040	arg1	pairs					1059:1063	native enzyme-substrate pairs	1035:1063	native enzyme-substrate pairs	1035:1063	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	3	14	theme	proven	394:399	arg1	relevance					409:417	proven disease relevance	394:417	proven disease relevance	394:417	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	0	15	theme	UDP-Sugar	58:66	arg1	Pairs					68:72	UDP-Sugar Pairs	58:72	UDP-Sugar Pairs	58:72	Engineering Orthogonal Polypeptide GalNAc-Transferase and UDP-Sugar Pairs.
31373799	7	16	theme	kinetics	1302:1309	arg1	investigation					1278:1290	A detailed investigation	1267:1290	A detailed investigation of enzyme kinetics and specificities	1267:1327	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	1	17	theme	O-GalNAc	109:116	arg1	glycans					119:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans	75:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans	75:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome.
31373799	7	18	theme	substrate	1442:1450	arg1	specificities					1452:1464	substrate specificities	1442:1464	substrate specificities	1442:1464	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	0	19	theme	Orthogonal	12:21	arg1	GalNAc-Transferase					35:52	Orthogonal Polypeptide GalNAc-Transferase	12:52	Orthogonal Polypeptide GalNAc-Transferase	12:52	Engineering Orthogonal Polypeptide GalNAc-Transferase and UDP-Sugar Pairs.
31373799	1	20	theme	O-Linked	75:82	arg1	glycans					119:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans	75:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans	75:125	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome.
31373799	7	21	theme	detailed	1269:1276	arg1	investigation					1278:1290	A detailed investigation	1267:1290	A detailed investigation of enzyme kinetics and specificities	1267:1327	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	3	22	theme	biological	474:483	arg1	function					485:492	biological function	474:492	biological function	474:492	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	2	23	theme	polypeptide	326:336	arg1	isoenzymes					269:278	20 distinct glycosyltransferase isoenzymes	237:278	20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation	237:319	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	2	23	theme	polypeptide	326:336	arg1	GalNAc-Ts					374:382	GalNAc-Ts	374:382	GalNAc-Ts	374:382	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	2	23	theme	polypeptide	326:336	arg1	N-acetylgalactosaminyltransferases					338:371	the polypeptide N-acetylgalactosaminyltransferases	322:371	the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts)	322:383	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	7	24	dep	robustness	1342:1351	arg1	paves					1415:1419	paves	1415:1419	paves the way for studying substrate specificities in living systems	1415:1482	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	7	24	dep	robustness	1342:1351	arg1	report					1383:1388	report	1383:1388	to faithfully report on GalNAc-T activity	1369:1409	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	5	25	theme	analogs	915:921	arg1	collection					834:843	a newly synthesized collection	814:843	a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs	814:921	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	6	26	gly	preglycosylated	1232:1246	arg1	substrate					1256:1264	a preglycosylated peptide substrate	1230:1264	a preglycosylated peptide substrate	1230:1264	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	6	27	theme	preglycosylated	1232:1246	arg1	substrate					1256:1264	a preglycosylated peptide substrate	1230:1264	a preglycosylated peptide substrate	1230:1264	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	0	28	theme	Polypeptide	23:33	arg1	GalNAc-Transferase					35:52	Orthogonal Polypeptide GalNAc-Transferase	12:52	Orthogonal Polypeptide GalNAc-Transferase	12:52	Engineering Orthogonal Polypeptide GalNAc-Transferase and UDP-Sugar Pairs.
31373799	5	29	contain	contain	759:765	arg1	GalNAc-Ts					719:727	Individual GalNAc-Ts	708:727	Individual GalNAc-Ts	708:727	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	5	29	contain	contain	759:765	arg2	hole					792:795	hole	792:795	hole	792:795	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	5	29	contain	contain	759:765	arg2	site					786:789	an enlarged active site	767:789	an enlarged active site (hole)	767:796	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	6	30	gly	nonglycosylated	1167:1181	arg1	substrates					1191:1200	nonglycosylated peptide substrates	1167:1200	nonglycosylated peptide substrates	1167:1200	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	5	31	theme	uridine	860:866	arg1	UDP-GalNAc					903:912	UDP-GalNAc	903:912	UDP-GalNAc	903:912	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	5	31	theme	uridine	860:866	arg1	N-acetylgalactosamine					880:900	20 (bumped) uridine diphosphate N-acetylgalactosamine	848:900	20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs	848:921	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	3	32	theme	GalNAc-Ts	459:467	arg1	activity					436:443	the activity	432:443	the activity of individual GalNAc-Ts	432:467	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	7	33	theme	approach	1360:1367	arg1	robustness					1342:1351	the robustness	1338:1351	the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems	1338:1482	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	2	34	theme	distinct	240:247	arg1	isoenzymes					269:278	20 distinct glycosyltransferase isoenzymes	237:278	20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation	237:319	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	2	34	theme	distinct	240:247	arg1	N-acetylgalactosaminyltransferases					338:371	the polypeptide N-acetylgalactosaminyltransferases	322:371	the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts)	322:383	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	5	35	theme	diphosphate	868:878	arg1	UDP-GalNAc					903:912	UDP-GalNAc	903:912	UDP-GalNAc	903:912	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	5	35	theme	diphosphate	868:878	arg1	N-acetylgalactosamine					880:900	20 (bumped) uridine diphosphate N-acetylgalactosamine	848:900	20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs	848:921	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	6	36	theme	multiple	1097:1104	arg1	-T2					1151:1153	-T2	1151:1153	-T2	1151:1153	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	6	36	theme	multiple	1097:1104	arg1	isoenzymes					1115:1124	multiple GalNAc-T isoenzymes	1097:1124	multiple GalNAc-T isoenzymes	1097:1124	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	6	36	theme	multiple	1097:1104	arg1	GalNAc-T1					1137:1145	GalNAc-T1	1137:1145	GalNAc-T1	1137:1145	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	5	37	theme	enlarged	770:777	arg1	hole					792:795	hole	792:795	hole	792:795	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	5	37	theme	enlarged	770:777	arg1	site					786:789	an enlarged active site	767:789	an enlarged active site (hole)	767:796	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	4	38	theme	GalNAc-T	680:687	arg1	activity					689:696	GalNAc-T activity	680:696	GalNAc-T activity	680:696	Here, we develop a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro.
31373799	5	39	theme	synthesized	822:832	arg1	collection					834:843	a newly synthesized collection	814:843	a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs	814:921	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	5	40	theme	active	779:784	arg1	hole					792:795	hole	792:795	hole	792:795	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	5	40	theme	active	779:784	arg1	site					786:789	an enlarged active site	767:789	an enlarged active site (hole)	767:796	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	6	41	theme	GalNAc-T	1106:1113	arg1	-T2					1151:1153	-T2	1151:1153	-T2	1151:1153	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	6	41	theme	GalNAc-T	1106:1113	arg1	isoenzymes					1115:1124	multiple GalNAc-T isoenzymes	1097:1124	multiple GalNAc-T isoenzymes	1097:1124	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	6	41	theme	GalNAc-T	1106:1113	arg1	GalNAc-T1					1137:1145	GalNAc-T1	1137:1145	GalNAc-T1	1137:1145	The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate.
31373799	1	42	theme	major	140:144	arg1	part					146:149	a major part	138:149	a major part of the human glycome	138:170	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome.
31373799	3	43	theme	individual	448:457	arg1	GalNAc-Ts					459:467	individual GalNAc-Ts	448:467	individual GalNAc-Ts	448:467	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	2	44	theme	complex	216:222	arg1	interplay					224:232	the complex interplay	212:232	the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts)	212:383	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	7	45	theme	GalNAc-T	1393:1400	arg1	activity					1402:1409	GalNAc-T activity	1393:1409	GalNAc-T activity	1393:1409	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	7	46	theme	living	1469:1474	arg1	systems					1476:1482	living systems	1469:1482	living systems	1469:1482	A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems.
31373799	5	47	theme	peptide	970:976	arg1	specificities					978:990	peptide specificities	970:990	peptide specificities	970:990	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	4	48	theme	chemical	642:649	arg1	system					660:665	a "bump-hole" chemical reporter system	628:665	a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro	628:705	Here, we develop a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro.
31373799	3	49	theme	complex	579:585	arg1	environment					598:608	a complex biological environment	577:608	a complex biological environment	577:608	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	3	50	theme	biological	587:596	arg1	environment					598:608	a complex biological environment	577:608	a complex biological environment	577:608	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	3	51	theme	tools	531:535	arg1	lack					523:526	a lack	521:526	a lack of tools to probe their substrate specificity in a complex biological environment	521:608	Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment.
31373799	4	52	theme	"	640:640	arg1	system					660:665	a "bump-hole" chemical reporter system	628:665	a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro	628:705	Here, we develop a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro.
31373799	5	53	theme	N-acetylgalactosamine	880:900	arg1	analogs					915:921	20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs	848:921	20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs	848:921	Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme-substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme-substrate pairs.
31373799	2	54	theme	isoenzymes	269:278	arg1	interplay					224:232	the complex interplay	212:232	the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts)	212:383	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	1	55	theme	human	158:162	arg1	glycome					164:170	the human glycome	154:170	the human glycome	154:170	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome.
31373799	2	56	theme	glycosyltransferase	249:267	arg1	isoenzymes					269:278	20 distinct glycosyltransferase isoenzymes	237:278	20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation	237:319	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	2	56	theme	glycosyltransferase	249:267	arg1	N-acetylgalactosaminyltransferases					338:371	the polypeptide N-acetylgalactosaminyltransferases	322:371	the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts)	322:383	They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts).
31373799	1	57	theme	glycome	164:170	arg1	part					146:149	a major part	138:149	a major part of the human glycome	138:170	O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome.
31373799	4	58	theme	reporter	651:658	arg1	system					660:665	a "bump-hole" chemical reporter system	628:665	a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro	628:705	Here, we develop a "bump-hole" chemical reporter system for studying GalNAc-T activity in vitro.
30504766	3	0	theme	nutrient	323:330	arg1	cues					332:335	nutrient cues	323:335	nutrient cues	323:335	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	6	1	theme	N-arachidonyl	737:749	arg1	AEA					765:767	AEA	765:767	AEA	765:767	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	1	theme	N-arachidonyl	737:749	arg1	ethanolamine					751:762	N-arachidonyl ethanolamine	737:762	N-arachidonyl ethanolamine (AEA)	737:768	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	1	theme	N-arachidonyl	737:749	arg1	cannabinoid					803:813	an endogenous appetite-inducing cannabinoid	771:813	an endogenous appetite-inducing cannabinoid (CB)	771:818	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	2	2	dep	Whether	155:161	arg1	increases					185:193	increases	185:193	increases appetite through the adipose-to-brain axis	185:236	Whether and how overnutrition increases appetite through the adipose-to-brain axis is unclear.
30504766	8	3	theme	adipose-to-brain	1057:1072	arg1	axis					1074:1077	an unexpected adipose-to-brain axis	1043:1077	an unexpected adipose-to-brain axis to induce hyperphagia and obesity	1043:1111	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	1	4	theme	obesity	146:152	arg1	development					131:141	the development	127:141	the development of obesity	127:152	Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity.
30504766	3	5	theme	proteins	373:380	arg1	O-GlcNAcylation					340:354	O-GlcNAcylation	340:354	O-GlcNAcylation of intracellular proteins at serine/threonine residues	340:409	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	8	6	theme	unexpected	1046:1055	arg1	axis					1074:1077	an unexpected adipose-to-brain axis	1043:1077	an unexpected adipose-to-brain axis to induce hyperphagia and obesity	1043:1111	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	1	7	theme	Palatable	60:68	arg1	sweet					85:89	sweet	85:89	sweet	85:89	Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity.
30504766	1	7	theme	Palatable	60:68	arg1	fat					77:79	fat	77:79	fat	77:79	Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity.
30504766	1	7	theme	Palatable	60:68	arg1	foods					70:74	Palatable foods	60:74	Palatable foods (fat and sweet)	60:90	Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity.
30504766	6	8	theme	transcriptional	660:674	arg1	activation					676:685	transcriptional activation	660:685	transcriptional activation of de novo lipid desaturation	660:715	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	4	9	theme	signaling	446:454	arg1	dysregulation					420:432	Chronic dysregulation	412:432	Chronic dysregulation of O-GlcNAc signaling	412:454	Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases.
30504766	8	10	theme	adipocyte	960:968	arg1	OGT					970:972	adipocyte OGT	960:972	adipocyte OGT	960:972	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	8	10	theme	adipocyte	960:968	arg1	sensor					983:988	a fat sensor	977:988	a fat sensor that regulates peripheral lipid signals	977:1028	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	3	11	from	residues	402:409	arg1	O-GlcNAcylation					340:354	O-GlcNAcylation	340:354	O-GlcNAcylation of intracellular proteins at serine/threonine residues	340:409	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	3	12	theme	O-linked	250:257	arg1	OGT					310:312	OGT	310:312	OGT	310:312	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	3	12	theme	O-linked	250:257	arg1	transferase					297:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase	250:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	250:313	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	4	13	theme	O-GlcNAc	437:444	arg1	signaling					446:454	O-GlcNAc signaling	437:454	O-GlcNAc signaling	437:454	Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases.
30504766	3	14	theme	intracellular	359:371	arg1	proteins					373:380	intracellular proteins	359:380	intracellular proteins	359:380	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	3	15	theme	beta-D-N-acetylglucosamine	259:284	arg1	OGT					310:312	OGT	310:312	OGT	310:312	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	3	15	theme	beta-D-N-acetylglucosamine	259:284	arg1	transferase					297:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase	250:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	250:313	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	5	16	theme	food	607:610	arg1	intake					612:617	baseline food intake	598:617	baseline food intake	598:617	Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake.
30504766	5	17	theme	high	540:543	arg1	hyperphagia					562:572	high fat diet-induced hyperphagia	540:572	high fat diet-induced hyperphagia	540:572	Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake.
30504766	5	18	theme	fat	545:547	arg1	hyperphagia					562:572	high fat diet-induced hyperphagia	540:572	high fat diet-induced hyperphagia	540:572	Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake.
30504766	3	19	link	O-linked	250:257	arg1	OGT					310:312	OGT	310:312	OGT	310:312	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	3	19	link	O-linked	250:257	arg1	transferase					297:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase	250:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	250:313	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	0	20	theme	Adipocyte	0:8	arg1	OGT					10:12	Adipocyte OGT	0:12	Adipocyte OGT	0:12	Adipocyte OGT governs diet-induced hyperphagia and obesity.
30504766	4	21	theme	Chronic	412:418	arg1	dysregulation					420:432	Chronic dysregulation	412:432	Chronic dysregulation of O-GlcNAc signaling	412:454	Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases.
30504766	6	22	theme	ethanolamine	751:762	arg1	accumulation					721:732	accumulation	721:732	accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB)	721:818	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	22	theme	ethanolamine	751:762	arg1	activation					676:685	transcriptional activation	660:685	transcriptional activation of de novo lipid desaturation	660:715	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	3	23	theme	serine/threonine	385:400	arg1	residues					402:409	serine/threonine residues	385:409	serine/threonine residues	385:409	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	5	24	theme	adipocyte	509:517	arg1	OGT					519:521	adipocyte OGT	509:521	adipocyte OGT	509:521	Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake.
30504766	7	25	theme	CB1	864:866	arg1	signaling					868:876	peripheral CB1 signaling	853:876	peripheral CB1 signaling	853:876	Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner.
30504766	7	26	theme	adipocyte	906:914	arg1	manner					930:935	an adipocyte OGT-dependent manner	903:935	an adipocyte OGT-dependent manner	903:935	Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner.
30504766	6	27	theme	Adipocyte	620:628	arg1	OGT					630:632	Adipocyte OGT	620:632	Adipocyte OGT	620:632	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	7	28	theme	signaling	868:876	arg1	manipulation					837:848	Pharmacological manipulation	821:848	Pharmacological manipulation of peripheral CB1 signaling	821:876	Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner.
30504766	3	29	theme	O-GlcNAc	287:294	arg1	OGT					310:312	OGT	310:312	OGT	310:312	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	3	29	theme	O-GlcNAc	287:294	arg1	transferase					297:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase	250:307	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	250:313	O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues.
30504766	0	30	theme	diet-induced	22:33	arg1	hyperphagia					35:45	diet-induced hyperphagia	22:45	diet-induced hyperphagia	22:45	Adipocyte OGT governs diet-induced hyperphagia and obesity.
30504766	8	31	theme	peripheral	1005:1014	arg1	signals					1022:1028	peripheral lipid signals	1005:1028	peripheral lipid signals	1005:1028	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	7	32	theme	OGT-dependent	916:928	arg1	manner					930:935	an adipocyte OGT-dependent manner	903:935	an adipocyte OGT-dependent manner	903:935	Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner.
30504766	2	33	theme	adipose-to-brain	216:231	arg1	axis					233:236	the adipose-to-brain axis	212:236	the adipose-to-brain axis	212:236	Whether and how overnutrition increases appetite through the adipose-to-brain axis is unclear.
30504766	7	34	theme	Pharmacological	821:835	arg1	manipulation					837:848	Pharmacological manipulation	821:848	Pharmacological manipulation of peripheral CB1 signaling	821:876	Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner.
30504766	8	35	theme	fat	979:981	arg1	OGT					970:972	adipocyte OGT	960:972	adipocyte OGT	960:972	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	8	35	theme	fat	979:981	arg1	sensor					983:988	a fat sensor	977:988	a fat sensor that regulates peripheral lipid signals	977:1028	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	6	36	dep	de	690:691	arg1	novo					693:696	novo	693:696	novo	693:696	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	5	37	theme	baseline	598:605	arg1	intake					612:617	baseline food intake	598:617	baseline food intake	598:617	Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake.
30504766	6	38	theme	desaturation	704:715	arg1	accumulation					721:732	accumulation	721:732	accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB)	721:818	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	38	theme	desaturation	704:715	arg1	activation					676:685	transcriptional activation	660:685	transcriptional activation of de novo lipid desaturation	660:715	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	8	39	theme	lipid	1016:1020	arg1	signals					1022:1028	peripheral lipid signals	1005:1028	peripheral lipid signals	1005:1028	These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
30504766	5	40	theme	diet-induced	549:560	arg1	hyperphagia					562:572	high fat diet-induced hyperphagia	540:572	high fat diet-induced hyperphagia	540:572	Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake.
30504766	1	41	dep	foods	70:74	arg1	sweet					85:89	sweet	85:89	sweet	85:89	Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity.
30504766	1	41	dep	foods	70:74	arg1	fat					77:79	fat	77:79	fat	77:79	Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity.
30504766	1	41	dep	foods	70:74	arg1	foods					70:74	Palatable foods	60:74	Palatable foods (fat and sweet)	60:90	Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity.
30504766	6	42	theme	lipid	698:702	arg1	desaturation					704:715	de novo lipid desaturation	690:715	de novo lipid desaturation	690:715	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	4	43	theme	metabolic	471:479	arg1	diseases					481:488	metabolic diseases	471:488	metabolic diseases	471:488	Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases.
30504766	6	44	theme	appetite-inducing	785:801	arg1	CB					816:817	CB	816:817	CB	816:817	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	44	theme	appetite-inducing	785:801	arg1	cannabinoid					803:813	an endogenous appetite-inducing cannabinoid	771:813	an endogenous appetite-inducing cannabinoid (CB)	771:818	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	44	theme	appetite-inducing	785:801	arg1	ethanolamine					751:762	N-arachidonyl ethanolamine	737:762	N-arachidonyl ethanolamine (AEA)	737:768	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	45	theme	endogenous	774:783	arg1	CB					816:817	CB	816:817	CB	816:817	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	45	theme	endogenous	774:783	arg1	cannabinoid					803:813	an endogenous appetite-inducing cannabinoid	771:813	an endogenous appetite-inducing cannabinoid (CB)	771:818	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	45	theme	endogenous	774:783	arg1	ethanolamine					751:762	N-arachidonyl ethanolamine	737:762	N-arachidonyl ethanolamine (AEA)	737:768	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	6	46	theme	de	690:691	arg1	desaturation					704:715	de novo lipid desaturation	690:715	de novo lipid desaturation	690:715	Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB).
30504766	7	47	theme	peripheral	853:862	arg1	signaling					868:876	peripheral CB1 signaling	853:876	peripheral CB1 signaling	853:876	Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner.
29774032	14	0	theme	O-GlcNAc	1643:1650	arg1	process					1684:1690	a natural process	1674:1690	a natural process by which physical activity modulates the immune system	1674:1745	O-GlcNAc modification could be a natural process by which physical activity modulates the immune system.
29774032	14	0	theme	O-GlcNAc	1643:1650	arg1	modification					1652:1663	O-GlcNAc modification	1643:1663	O-GlcNAc modification	1643:1663	O-GlcNAc modification could be a natural process by which physical activity modulates the immune system.
29774032	8	1	theme	O-GlcNAc	964:971	arg1	distribution					948:959	The distribution	944:959	The distribution of O-GlcNAc in WBC subpopulations	944:993	The distribution of O-GlcNAc in WBC subpopulations was assessed by flow cytometry.
29774032	2	2	theme	oxidative	377:385	arg1	stress					387:392	oxidative stress	377:392	oxidative stress	377:392	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	4	3	theme	human	574:578	arg1	volunteers					580:589	human volunteers	574:589	human volunteers	574:589	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	0	4	theme	Single	69:74	arg1	Bout					76:79	a Single Bout	67:79	a Single Bout of Physical Exercise	67:100	Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.
29774032	4	5	theme	O-GlcNAc	528:535	arg1	levels					537:542	O-GlcNAc levels	528:542	O-GlcNAc levels	528:542	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	6	6	theme	cell	778:781	arg1	counts					783:788	cell counts	778:788	cell counts	778:788	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	13	7	theme	short-term	1586:1595	arg1	exercise					1597:1604	short-term exercise	1586:1604	short-term exercise	1586:1604	Conclusion Our results indicate that short-term exercise impacts the O-GlcNAc status of WBCs.
29774032	12	8	theme	Flow	1450:1453	arg1	cytometry					1455:1463	Flow cytometry	1450:1463	Flow cytometry	1450:1463	Flow cytometry revealed that most of this change could be attributed to lymphocytes and monocytes.
29774032	0	9	theme	Physical	84:91	arg1	Exercise					93:100	Physical Exercise	84:100	Physical Exercise	84:100	Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.
29774032	6	10	theme	2-mile	848:853	arg1	exercise					838:845	exercise	838:845	exercise (2-mile run)	838:858	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	6	10	theme	2-mile	848:853	arg1	run					855:857	2-mile run	848:857	2-mile run	848:857	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	8	11	theme	WBC	976:978	arg1	subpopulations					980:993	WBC subpopulations	976:993	WBC subpopulations	976:993	The distribution of O-GlcNAc in WBC subpopulations was assessed by flow cytometry.
29774032	9	12	theme	creatinine	1110:1119	arg1	Elevation					1035:1043	Elevation	1035:1043	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1027:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	5	13	theme	male	658:661	arg1	n = 6					675:679	n = 6	675:679	n = 6	675:679	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	5	13	theme	male	658:661	arg1	volunteers					663:672	Young (age 30 ± 5.2), healthy male volunteers	628:672	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6)	620:680	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	15	14	theme	Further	1748:1754	arg1	research					1756:1763	Further research	1748:1763	Further research	1748:1763	Further research could elucidate the role of O-GlcNAc during exercise and validate O-GlcNAc as a biomarker for fitness assessment.
29774032	4	15	theme	volunteers	580:589	arg1	WBC					566:568	WBC	566:568	WBC	566:568	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	4	15	theme	volunteers	580:589	arg1	cells					559:563	white blood cells	547:563	white blood cells (WBC) of human volunteers	547:589	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	13	16	dep	Conclusion	1549:1558	arg1	indicate					1572:1579	indicate	1572:1579	indicate that short-term exercise impacts the O-GlcNAc status of WBCs	1572:1640	Conclusion Our results indicate that short-term exercise impacts the O-GlcNAc status of WBCs.
29774032	6	17	theme	exercise	838:845	arg1	bout					830:833	a single bout	821:833	a single bout of exercise (2-mile run)	821:858	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	5	18	theme	Young	628:632	arg1	n = 6					675:679	n = 6	675:679	n = 6	675:679	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	5	18	theme	Young	628:632	arg1	volunteers					663:672	Young (age 30 ± 5.2), healthy male volunteers	628:672	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6)	620:680	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	13	19	theme	WBCs	1637:1640	arg1	status					1627:1632	the O-GlcNAc status	1614:1632	the O-GlcNAc status of WBCs	1614:1640	Conclusion Our results indicate that short-term exercise impacts the O-GlcNAc status of WBCs.
29774032	2	20	theme	O-GlcNAc	293:300	arg1	regulation					302:311	O-GlcNAc regulation	293:311	O-GlcNAc regulation	293:311	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	1	21	theme	posttranslational	175:191	arg1	modification					193:204	a dynamic posttranslational modification	165:204	a dynamic posttranslational modification influencing the function of many intracellular proteins	165:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	21	theme	posttranslational	175:191	arg1	N-acetylglucosamine					131:149	Background Protein O-linked N-acetylglucosamine	103:149	Background Protein O-linked N-acetylglucosamine (O-GlcNAc)	103:160	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	9	22	from	6.9 ± 1.7 mM	1095:1106	arg1	acid					1061:1064	serum lactic acid	1048:1064	serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM)	1048:1107	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	22	from	6.9 ± 1.7 mM	1095:1106	arg1	dehydrogenase					1174:1186	lactate dehydrogenase	1166:1186	lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1166:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	22	from	6.9 ± 1.7 mM	1095:1106	arg1	creatinine					1110:1119	creatinine	1110:1119	creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM)	1110:1159	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	22	from	6.9 ± 1.7 mM	1095:1106	arg1	Elevation					1035:1043	Elevation	1035:1043	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1027:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	0	23	theme	Exercise	93:100	arg1	Bout					76:79	a Single Bout	67:79	a Single Bout of Physical Exercise	67:100	Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.
29774032	9	24	theme	exercise	1252:1259	arg1	effect					1242:1247	the effect	1238:1247	the effect of exercise	1238:1259	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	13	25	theme	O-GlcNAc	1618:1625	arg1	status					1627:1632	the O-GlcNAc status	1614:1632	the O-GlcNAc status of WBCs	1614:1640	Conclusion Our results indicate that short-term exercise impacts the O-GlcNAc status of WBCs.
29774032	3	26	theme	few	408:410	arg1	studies					426:432	a few contradictory studies	406:432	a few contradictory studies based on animal models	406:455	Aside from a few contradictory studies based on animal models, the effect of exercise on O-GlcNAc is unexplored.
29774032	11	27	theme	modified	1358:1365	arg1	proteins					1367:1374	O-GlcNAc modified proteins	1349:1374	O-GlcNAc modified proteins	1349:1374	The level of O-GlcNAc modified proteins in WBCs showed significant elevation after exercise (85 ± 51%, p < 0.05).
29774032	1	28	theme	dynamic	167:173	arg1	modification					193:204	a dynamic posttranslational modification	165:204	a dynamic posttranslational modification influencing the function of many intracellular proteins	165:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	28	theme	dynamic	167:173	arg1	N-acetylglucosamine					131:149	Background Protein O-linked N-acetylglucosamine	103:149	Background Protein O-linked N-acetylglucosamine (O-GlcNAc)	103:160	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	0	29	theme	O-GlcNAc	8:15	arg1	Modification					17:28	Protein O-GlcNAc Modification	0:28	Protein O-GlcNAc Modification	0:28	Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.
29774032	15	30	theme	O-GlcNAc	1793:1800	arg1	role					1785:1788	the role	1781:1788	the role of O-GlcNAc	1781:1800	Further research could elucidate the role of O-GlcNAc during exercise and validate O-GlcNAc as a biomarker for fitness assessment.
29774032	5	31	theme	age	635:637	arg1	30 ± 5.2					639:646	age 30 ± 5.2	635:646	age 30 ± 5.2	635:646	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	6	32	theme	necro	758:762	arg1	-enzymes					764:771	"necro"-enzymes	757:771	"necro"-enzymes	757:771	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	2	33	theme	stress	339:344	arg1	states					346:351	various stress states	331:351	various stress states	331:351	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	2	33	theme	stress	339:344	arg1	ischemia					364:371	ischemia	364:371	ischemia	364:371	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	2	33	theme	stress	339:344	arg1	stress					387:392	oxidative stress	377:392	oxidative stress	377:392	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	11	34	theme	proteins	1367:1374	arg1	level					1340:1344	The level	1336:1344	The level of O-GlcNAc modified proteins in WBCs	1336:1382	The level of O-GlcNAc modified proteins in WBCs showed significant elevation after exercise (85 ± 51%, p < 0.05).
29774032	3	35	theme	animal	443:448	arg1	models					450:455	animal models	443:455	animal models	443:455	Aside from a few contradictory studies based on animal models, the effect of exercise on O-GlcNAc is unexplored.
29774032	0	36	theme	Protein	0:6	arg1	Modification					17:28	Protein O-GlcNAc Modification	0:28	Protein O-GlcNAc Modification	0:28	Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.
29774032	2	37	theme	various	331:337	arg1	states					346:351	various stress states	331:351	various stress states	331:351	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	2	37	theme	various	331:337	arg1	ischemia					364:371	ischemia	364:371	ischemia	364:371	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	2	37	theme	various	331:337	arg1	stress					387:392	oxidative stress	377:392	oxidative stress	377:392	Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress.
29774032	9	38	dep	6.9 ± 1.7 mM	1095:1106	arg1	to					1092:1093	to	1092:1093	to	1092:1093	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	11	39	from	level	1340:1344	arg1	WBCs					1379:1382	WBCs	1379:1382	WBCs	1379:1382	The level of O-GlcNAc modified proteins in WBCs showed significant elevation after exercise (85 ± 51%, p < 0.05).
29774032	4	40	theme	physical	601:608	arg1	exercise					610:617	physical exercise	601:617	physical exercise	601:617	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	7	41	theme	WBC	866:868	arg1	samples					870:876	WBC samples	866:876	WBC samples	866:876	From WBC samples, we performed western blots to detect O-GlcNAc modified proteins.
29774032	7	42	theme	western	892:898	arg1	blots					900:904	western blots	892:904	western blots	892:904	From WBC samples, we performed western blots to detect O-GlcNAc modified proteins.
29774032	3	43	theme	exercise	472:479	arg1	effect					462:467	the effect	458:467	the effect of exercise on O-GlcNAc	458:491	Aside from a few contradictory studies based on animal models, the effect of exercise on O-GlcNAc is unexplored.
29774032	7	44	theme	modified	925:932	arg1	proteins					934:941	O-GlcNAc modified proteins	916:941	O-GlcNAc modified proteins	916:941	From WBC samples, we performed western blots to detect O-GlcNAc modified proteins.
29774032	9	45	dep	380.5 ± 33.2 U/L	1210:1225	arg1	to					1207:1208	to	1207:1208	to	1207:1208	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	8	46	theme	flow	1011:1014	arg1	cytometry					1016:1024	flow cytometry	1011:1024	flow cytometry	1011:1024	The distribution of O-GlcNAc in WBC subpopulations was assessed by flow cytometry.
29774032	6	47	theme	single	823:828	arg1	bout					830:833	a single bout	821:833	a single bout of exercise (2-mile run)	821:858	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	11	48	theme	significant	1391:1401	arg1	elevation					1403:1411	significant elevation	1391:1411	significant elevation	1391:1411	The level of O-GlcNAc modified proteins in WBCs showed significant elevation after exercise (85 ± 51%, p < 0.05).
29774032	9	49	theme	serum	1048:1052	arg1	acid					1061:1064	serum lactic acid	1048:1064	serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM)	1048:1107	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	0	50	theme	White	43:47	arg1	Cells					55:59	White Blood Cells	43:59	White Blood Cells	43:59	Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.
29774032	10	51	dep	increased	1291:1299	arg1	8.4 ± 1.4 G/L					1320:1332	8.4 ± 1.4 G/L	1320:1332	8.4 ± 1.4 G/L	1320:1332	WBC count also significantly increased (from 6.6 ± 1.0 to 8.4 ± 1.4 G/L).
29774032	10	52	dep	8.4 ± 1.4 G/L	1320:1332	arg1	to					1317:1318	to	1317:1318	to	1317:1318	WBC count also significantly increased (from 6.6 ± 1.0 to 8.4 ± 1.4 G/L).
29774032	9	53	theme	lactic	1054:1059	arg1	acid					1061:1064	serum lactic acid	1048:1064	serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM)	1048:1107	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	11	54	dep	exercise	1419:1426	arg1	p < 0.05					1439:1446	p < 0.05	1439:1446	p < 0.05	1439:1446	The level of O-GlcNAc modified proteins in WBCs showed significant elevation after exercise (85 ± 51%, p < 0.05).
29774032	11	54	dep	exercise	1419:1426	arg1	%					1436:1436	85 ± 51%	1429:1436	85 ± 51%	1429:1436	The level of O-GlcNAc modified proteins in WBCs showed significant elevation after exercise (85 ± 51%, p < 0.05).
29774032	9	55	theme	lactate	1166:1172	arg1	dehydrogenase					1174:1186	lactate dehydrogenase	1166:1186	lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1166:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	3	56	from	effect	462:467	arg1	O-GlcNAc					484:491	O-GlcNAc	484:491	O-GlcNAc	484:491	Aside from a few contradictory studies based on animal models, the effect of exercise on O-GlcNAc is unexplored.
29774032	3	57	theme	contradictory	412:424	arg1	studies					426:432	a few contradictory studies	406:432	a few contradictory studies based on animal models	406:455	Aside from a few contradictory studies based on animal models, the effect of exercise on O-GlcNAc is unexplored.
29774032	14	58	theme	natural	1676:1682	arg1	process					1684:1690	a natural process	1674:1690	a natural process by which physical activity modulates the immune system	1674:1745	O-GlcNAc modification could be a natural process by which physical activity modulates the immune system.
29774032	14	58	theme	natural	1676:1682	arg1	modification					1652:1663	O-GlcNAc modification	1643:1663	O-GlcNAc modification	1643:1663	O-GlcNAc modification could be a natural process by which physical activity modulates the immune system.
29774032	1	59	link	O-linked	122:129	arg1	O-GlcNAc					152:159	O-GlcNAc	152:159	O-GlcNAc	152:159	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	59	link	O-linked	122:129	arg1	N-acetylglucosamine					131:149	Background Protein O-linked N-acetylglucosamine	103:149	Background Protein O-linked N-acetylglucosamine (O-GlcNAc)	103:160	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	59	link	O-linked	122:129	arg1	modification					193:204	a dynamic posttranslational modification	165:204	a dynamic posttranslational modification influencing the function of many intracellular proteins	165:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	9	60	theme	dehydrogenase	1174:1186	arg1	Elevation					1035:1043	Elevation	1035:1043	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1027:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	61	from	Elevation	1035:1043	arg1	380.5 ± 33.2 U/L					1210:1225	380.5 ± 33.2 U/L	1210:1225	380.5 ± 33.2 U/L	1210:1225	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	61	from	Elevation	1035:1043	arg1	6.9 ± 1.7 mM					1095:1106	6.9 ± 1.7 mM	1095:1106	6.9 ± 1.7 mM	1095:1106	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	62	dep	Results	1027:1033	arg1	Elevation					1035:1043	Elevation	1035:1043	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1027:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	1	63	theme	Background	103:112	arg1	O-GlcNAc					152:159	O-GlcNAc	152:159	O-GlcNAc	152:159	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	63	theme	Background	103:112	arg1	N-acetylglucosamine					131:149	Background Protein O-linked N-acetylglucosamine	103:149	Background Protein O-linked N-acetylglucosamine (O-GlcNAc)	103:160	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	63	theme	Background	103:112	arg1	modification					193:204	a dynamic posttranslational modification	165:204	a dynamic posttranslational modification influencing the function of many intracellular proteins	165:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	0	64	theme	Blood	49:53	arg1	Cells					55:59	White Blood Cells	43:59	White Blood Cells	43:59	Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.
29774032	4	65	theme	blood	553:557	arg1	WBC					566:568	WBC	566:568	WBC	566:568	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	4	65	theme	blood	553:557	arg1	cells					559:563	white blood cells	547:563	white blood cells (WBC) of human volunteers	547:589	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	15	66	theme	fitness	1859:1865	arg1	assessment					1867:1876	fitness assessment	1859:1876	fitness assessment	1859:1876	Further research could elucidate the role of O-GlcNAc during exercise and validate O-GlcNAc as a biomarker for fitness assessment.
29774032	1	67	theme	Protein	114:120	arg1	O-GlcNAc					152:159	O-GlcNAc	152:159	O-GlcNAc	152:159	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	67	theme	Protein	114:120	arg1	N-acetylglucosamine					131:149	Background Protein O-linked N-acetylglucosamine	103:149	Background Protein O-linked N-acetylglucosamine (O-GlcNAc)	103:160	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	67	theme	Protein	114:120	arg1	modification					193:204	a dynamic posttranslational modification	165:204	a dynamic posttranslational modification influencing the function of many intracellular proteins	165:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	4	68	theme	white	547:551	arg1	WBC					566:568	WBC	566:568	WBC	566:568	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	4	68	theme	white	547:551	arg1	cells					559:563	white blood cells	547:563	white blood cells (WBC) of human volunteers	547:589	Purpose To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise.
29774032	9	69	from	380.5 ± 33.2 U/L	1210:1225	arg1	acid					1061:1064	serum lactic acid	1048:1064	serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM)	1048:1107	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	69	from	380.5 ± 33.2 U/L	1210:1225	arg1	dehydrogenase					1174:1186	lactate dehydrogenase	1166:1186	lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1166:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	69	from	380.5 ± 33.2 U/L	1210:1225	arg1	creatinine					1110:1119	creatinine	1110:1119	creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM)	1110:1159	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	9	69	from	380.5 ± 33.2 U/L	1210:1225	arg1	Elevation					1035:1043	Elevation	1035:1043	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1027:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	10	70	theme	WBC	1262:1264	arg1	count					1266:1270	WBC count	1262:1270	WBC count	1262:1270	WBC count also significantly increased (from 6.6 ± 1.0 to 8.4 ± 1.4 G/L).
29774032	1	71	theme	O-linked	122:129	arg1	O-GlcNAc					152:159	O-GlcNAc	152:159	O-GlcNAc	152:159	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	71	theme	O-linked	122:129	arg1	N-acetylglucosamine					131:149	Background Protein O-linked N-acetylglucosamine	103:149	Background Protein O-linked N-acetylglucosamine (O-GlcNAc)	103:160	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	1	71	theme	O-linked	122:129	arg1	modification					193:204	a dynamic posttranslational modification	165:204	a dynamic posttranslational modification influencing the function of many intracellular proteins	165:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	5	72	dep	Methods	620:626	arg1	n = 6					675:679	n = 6	675:679	n = 6	675:679	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	5	72	dep	Methods	620:626	arg1	volunteers					663:672	Young (age 30 ± 5.2), healthy male volunteers	628:672	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6)	620:680	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	1	73	theme	many	234:237	arg1	proteins					253:260	many intracellular proteins	234:260	many intracellular proteins	234:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	9	74	theme	acid	1061:1064	arg1	Elevation					1035:1043	Elevation	1035:1043	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L)	1027:1226	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
29774032	14	75	theme	immune	1733:1738	arg1	system					1740:1745	the immune system	1729:1745	the immune system	1729:1745	O-GlcNAc modification could be a natural process by which physical activity modulates the immune system.
29774032	1	76	theme	intracellular	239:251	arg1	proteins					253:260	many intracellular proteins	234:260	many intracellular proteins	234:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	6	77	theme	Blood	711:715	arg1	metabolites					738:748	metabolites	738:748	metabolites	738:748	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	6	77	theme	Blood	711:715	arg1	counts					783:788	cell counts	778:788	cell counts	778:788	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	6	77	theme	Blood	711:715	arg1	parameters					717:726	Blood parameters	711:726	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts	711:788	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	6	77	theme	Blood	711:715	arg1	-enzymes					764:771	"necro"-enzymes	757:771	"necro"-enzymes	757:771	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	6	77	theme	Blood	711:715	arg1	ions					751:754	ions	751:754	ions	751:754	Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run).
29774032	8	78	from	distribution	948:959	arg1	subpopulations					980:993	WBC subpopulations	976:993	WBC subpopulations	976:993	The distribution of O-GlcNAc in WBC subpopulations was assessed by flow cytometry.
29774032	1	79	theme	proteins	253:260	arg1	function					222:229	the function	218:229	the function of many intracellular proteins	218:260	Background Protein O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins.
29774032	5	80	dep	Young	628:632	arg1	30 ± 5.2					639:646	age 30 ± 5.2	635:646	age 30 ± 5.2	635:646	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	5	80	dep	Young	628:632	arg1	healthy					650:656	healthy	650:656	healthy	650:656	Methods Young (age 30 ± 5.2), healthy male volunteers (n = 6) were enlisted for the study.
29774032	14	81	theme	physical	1701:1708	arg1	activity					1710:1717	physical activity	1701:1717	physical activity	1701:1717	O-GlcNAc modification could be a natural process by which physical activity modulates the immune system.
29774032	9	82	dep	102.2 ± 7.0 μM	1145:1158	arg1	77.5 ± 6.3 U/L					1127:1140	77.5 ± 6.3 U/L	1127:1140	77.5 ± 6.3 U/L	1127:1140	Results Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise.
31723224	6	0	theme	Ser23	1123:1127	arg1	variant					1129:1135	the Ser23 variant	1119:1135	the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele	1119:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	1	1	theme	5-HT2CR	318:324	arg1	pharmacology					326:337	impact 5-HT2CR pharmacology	311:337	impact 5-HT2CR pharmacology	311:337	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	6	2	attach	present	1081:1087	arg2	Cys23					1053:1057	the Cys23	1049:1057	the Cys23	1049:1057	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	2	attach	present	1081:1087	arg2	present					1081:1087	present	1081:1087	present	1081:1087	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	2	attach	present	1081:1087	arg2	5-HT2CR					1069:1075	Ser23 5-HT2CR	1063:1075	Ser23 5-HT2CR	1063:1075	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	2	attach	present	1081:1087	arg1	pathway					1106:1112	the recycling pathway	1092:1112	the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele	1092:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	3	3	theme	cell	501:504	arg1	lines					506:510	cell lines	501:510	cell lines stably expressing the wild-type Cys23 or the Ser23 variant	501:569	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	3	4	theme	Cys23	692:696	arg1	lines					703:707	the Ser23 versus the Cys23 cell lines	671:707	lines	703:707	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	7	5	with	pathway	1288:1294	arg1	effect					1304:1309	no effect	1301:1309	no effect on the Cys23 allele	1301:1329	Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele.
31723224	6	6	from	present	1081:1087	arg1	pathway					1106:1112	the recycling pathway	1092:1112	the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele	1092:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	1	7	theme	human	182:186	arg1	receptor					205:212	human serotonin 5-HT2C receptor	182:212	the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	178:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	1	7	theme	human	182:186	arg1	5-HT2CR					215:221	5-HT2CR	215:221	5-HT2CR	215:221	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	7	8	theme	recycling	1278:1286	arg1	pathway					1288:1294	the recycling pathway	1274:1294	the recycling pathway with no effect on the Cys23 allele	1274:1329	Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele.
31723224	4	9	theme	plasma	764:769	arg1	localization					780:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR.
31723224	4	10	theme	lower	744:748	arg1	localization					780:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR.
31723224	6	11	with	pathway	1106:1112	arg1	variant					1129:1135	the Ser23 variant	1119:1135	the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele	1119:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	5	12	link	O-linked	865:872	arg1	glycosylation					874:886	O-linked glycosylation	865:886	O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23,	865:937	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	5	12	link	O-linked	865:872	arg1	mechanism					967:975	a post-translational mechanism	946:975	a post-translational mechanism which alters its localization within the Golgi apparatus	946:1032	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	4	13	theme	5-HT2CR	756:762	arg1	localization					780:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR.
31723224	1	14	theme	amino	269:273	arg1	codon					280:284	amino acid codon 23	269:287	amino acid codon 23 (Cys23Ser)	269:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	1	14	theme	amino	269:273	arg1	Cys23Ser					290:297	Cys23Ser	290:297	Cys23Ser	290:297	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	8	15	from	impact	1486:1491	arg1	individuals					1529:1539	individuals	1529:1539	individuals expressing the Cys23Ser SNP	1529:1567	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	1	16	theme	cellular	344:351	arg1	level					365:369	a cellular and systems level	342:369	a cellular and systems level	342:369	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	6	17	theme	Ser23	1063:1067	arg1	5-HT2CR					1069:1075	Ser23 5-HT2CR	1063:1075	Ser23 5-HT2CR	1063:1075	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	8	18	theme	Ser23	1352:1356	arg1	variant					1358:1364	the Ser23 variant	1348:1364	the Ser23 variant	1348:1364	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	5	19	theme	variant	901:907	arg1	glycosylation					874:886	O-linked glycosylation	865:886	O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23,	865:937	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	5	19	theme	variant	901:907	arg1	mechanism					967:975	a post-translational mechanism	946:975	a post-translational mechanism which alters its localization within the Golgi apparatus	946:1032	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	1	20	theme	serotonin	188:196	arg1	receptor					205:212	human serotonin 5-HT2C receptor	182:212	the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	178:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	1	20	theme	serotonin	188:196	arg1	5-HT2CR					215:221	5-HT2CR	215:221	5-HT2CR	215:221	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	2	21	from	localization	472:483	arg1	vitro					488:492	vitro	488:492	vitro	488:492	We hypothesized that the Cys23Ser alters 5-HT2CR intracellular signaling via changes in subcellular localization in vitro.
31723224	3	22	theme	wild-type	534:542	arg1	Cys23					544:548	the wild-type Cys23	530:548	the wild-type Cys23	530:548	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	6	23	theme	recycling	1096:1104	arg1	pathway					1106:1112	the recycling pathway	1092:1112	the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele	1092:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	1	24	theme	5-HT2C	198:203	arg1	receptor					205:212	human serotonin 5-HT2C receptor	182:212	the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	178:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	1	24	theme	5-HT2C	198:203	arg1	5-HT2CR					215:221	5-HT2CR	215:221	5-HT2CR	215:221	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	0	25	theme	5-HT2C	10:15	arg1	Cys23Ser					26:33	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.
31723224	1	26	theme	systems	357:363	arg1	level					365:369	a cellular and systems level	342:369	a cellular and systems level	342:369	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	7	27	theme	5-HT2CR	1233:1239	arg1	Agonism					1218:1224	Agonism	1218:1224	Agonism of the 5-HT2CR	1218:1239	Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele.
31723224	6	28	theme	early	1178:1182	arg1	endosome					1184:1191	the early endosome	1174:1191	the early endosome	1174:1191	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	2	29	from	changes	449:455	arg1	localization					472:483	subcellular localization	460:483	subcellular localization in vitro	460:492	We hypothesized that the Cys23Ser alters 5-HT2CR intracellular signaling via changes in subcellular localization in vitro.
31723224	1	30	theme	receptor	205:212	arg1	gene					224:227	the human serotonin 5-HT2C receptor (5-HT2CR) gene	178:227	the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	178:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	0	31	theme	Serotonin	0:8	arg1	Cys23Ser					26:33	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.
31723224	1	32	theme	acid	275:278	arg1	codon					280:284	amino acid codon 23	269:287	amino acid codon 23 (Cys23Ser)	269:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	1	32	theme	acid	275:278	arg1	Cys23Ser					290:297	Cys23Ser	290:297	Cys23Ser	290:297	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	1	33	from	codon	280:284	arg1	serine					259:264	a serine	257:264	a serine at amino acid codon 23 (Cys23Ser)	257:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	8	34	theme	receptor	1504:1511	arg1	pharmacology					1513:1524	receptor pharmacology	1504:1524	receptor pharmacology	1504:1524	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	5	35	theme	post-translational	948:965	arg1	mechanism					967:975	a post-translational mechanism	946:975	a post-translational mechanism which alters its localization within the Golgi apparatus	946:1032	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	5	35	theme	post-translational	948:965	arg1	glycosylation					874:886	O-linked glycosylation	865:886	O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23,	865:937	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	5	36	theme	wild-type	922:930	arg1	Cys23					932:936	the wild-type Cys23	918:936	the wild-type Cys23	918:936	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	2	37	theme	intracellular	421:433	arg1	signaling					435:443	5-HT2CR intracellular signaling	413:443	5-HT2CR intracellular signaling	413:443	We hypothesized that the Cys23Ser alters 5-HT2CR intracellular signaling via changes in subcellular localization in vitro.
31723224	5	38	theme	Subcellular	819:829	arg1	studies					844:850	Subcellular localization studies	819:850	Subcellular localization studies	819:850	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	4	39	theme	Ser23	750:754	arg1	localization					780:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR.
31723224	7	40	from	effect	1304:1309	arg1	allele					1324:1329	the Cys23 allele	1314:1329	the Cys23 allele	1314:1329	Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele.
31723224	7	41	theme	Cys23	1318:1322	arg1	allele					1324:1329	the Cys23 allele	1314:1329	the Cys23 allele	1314:1329	Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele.
31723224	0	42	theme	Receptor	17:24	arg1	Cys23Ser					26:33	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.
31723224	6	43	theme	Cys23	1204:1208	arg1	allele					1210:1215	the Cys23 allele	1200:1215	the Cys23 allele	1200:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	3	44	theme	Ser23	557:561	arg1	variant					563:569	the Ser23 variant	553:569	the Ser23 variant	553:569	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	5	45	theme	O-linked	865:872	arg1	glycosylation					874:886	O-linked glycosylation	865:886	O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23,	865:937	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	5	45	theme	O-linked	865:872	arg1	mechanism					967:975	a post-translational mechanism	946:975	a post-translational mechanism which alters its localization within the Golgi apparatus	946:1032	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	0	46	theme	Nucleotide	42:51	arg1	Polymorphism					53:64	Single Nucleotide Polymorphism	35:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.
31723224	8	47	theme	Cys23	1460:1464	arg1	allele					1466:1471	the wild-type Cys23 allele	1446:1471	the wild-type Cys23 allele	1446:1471	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	4	48	theme	Cys23	804:808	arg1	5-HT2CR					810:816	the Cys23 5-HT2CR	800:816	the Cys23 5-HT2CR	800:816	Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR.
31723224	1	49	theme	gene	224:227	arg1	polymorphism					162:173	A non-synonymous single nucleotide polymorphism	127:173	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	127:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	0	50	theme	Single	35:40	arg1	Polymorphism					53:64	Single Nucleotide Polymorphism	35:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.
31723224	2	51	theme	subcellular	460:470	arg1	localization					472:483	subcellular localization	460:483	subcellular localization in vitro	460:492	We hypothesized that the Cys23Ser alters 5-HT2CR intracellular signaling via changes in subcellular localization in vitro.
31723224	6	52	contain	having	1137:1142	arg1	variant					1129:1135	the Ser23 variant	1119:1135	the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele	1119:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	52	contain	having	1137:1142	arg2	allele					1210:1215	the Cys23 allele	1200:1215	the Cys23 allele	1200:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	52	contain	having	1137:1142	arg2	colocalization					1154:1167	decreased colocalization	1144:1167	decreased colocalization with the early endosome	1144:1191	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	5	53	theme	localization	831:842	arg1	studies					844:850	Subcellular localization studies	819:850	Subcellular localization studies	819:850	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	6	54	with	colocalization	1154:1167	arg1	endosome					1184:1191	the early endosome	1174:1191	the early endosome	1174:1191	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	3	55	theme	decreased	632:640	arg1	potency					642:648	decreased potency	632:648	decreased potency	632:648	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	8	56	theme	localization	1418:1429	arg1	profile					1431:1437	a distinct pharmacological and subcellular localization profile	1375:1437	a distinct pharmacological and subcellular localization profile	1375:1437	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	3	57	theme	cell	698:701	arg1	lines					703:707	the Ser23 versus the Cys23 cell lines	671:707	lines	703:707	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	5	58	theme	Cys23	932:936	arg1	glycosylation					874:886	O-linked glycosylation	865:886	O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23,	865:937	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	5	58	theme	Cys23	932:936	arg1	mechanism					967:975	a post-translational mechanism	946:975	a post-translational mechanism which alters its localization within the Golgi apparatus	946:1032	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	8	59	theme	pharmacology	1513:1524	arg1	aspects					1493:1499	aspects	1493:1499	aspects of receptor pharmacology	1493:1524	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	8	60	theme	subcellular	1406:1416	arg1	profile					1431:1437	a distinct pharmacological and subcellular localization profile	1375:1437	a distinct pharmacological and subcellular localization profile	1375:1437	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	1	61	theme	non-synonymous	129:142	arg1	polymorphism					162:173	A non-synonymous single nucleotide polymorphism	127:173	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	127:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	3	62	theme	intracellular	597:609	arg1	release					619:625	intracellular calcium release	597:625	intracellular calcium release	597:625	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	3	63	theme	calcium	611:617	arg1	release					619:625	intracellular calcium release	597:625	intracellular calcium release	597:625	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	0	64	dep	Cys23Ser	26:33	arg1	Polymorphism					53:64	Single Nucleotide Polymorphism	35:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism	0:64	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.
31723224	8	65	theme	pharmacological	1386:1400	arg1	profile					1431:1437	a distinct pharmacological and subcellular localization profile	1375:1437	a distinct pharmacological and subcellular localization profile	1375:1437	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	1	66	theme	single	144:149	arg1	polymorphism					162:173	A non-synonymous single nucleotide polymorphism	127:173	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	127:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	5	67	gly	glycosylation	874:886	arg1	variant					901:907	the Ser23 variant	891:907	the Ser23 variant	891:907	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	5	67	gly	glycosylation	874:886	arg1	Cys23					932:936	the wild-type Cys23	918:936	the wild-type Cys23	918:936	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	6	68	located	present	1081:1087	arg2	Cys23					1053:1057	the Cys23	1049:1057	the Cys23	1049:1057	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	68	located	present	1081:1087	arg2	present					1081:1087	present	1081:1087	present	1081:1087	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	68	located	present	1081:1087	arg2	5-HT2CR					1069:1075	Ser23 5-HT2CR	1063:1075	Ser23 5-HT2CR	1063:1075	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	68	located	present	1081:1087	arg1	pathway					1106:1112	the recycling pathway	1092:1112	the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele	1092:1215	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	4	69	theme	membrane	771:778	arg1	localization					780:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	lower Ser23 5-HT2CR plasma membrane localization	744:791	Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR.
31723224	3	70	theme	peak	654:657	arg1	response					659:666	peak response	654:666	peak response	654:666	Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines.
31723224	5	71	theme	Golgi	1018:1022	arg1	apparatus					1024:1032	the Golgi apparatus	1014:1032	the Golgi apparatus	1014:1032	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	6	72	from	pathway	1106:1112	arg1	present					1081:1087	present	1081:1087	present	1081:1087	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	6	72	from	pathway	1106:1112	arg1	Cys23					1053:1057	the Cys23	1049:1057	the Cys23	1049:1057	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	1	73	theme	nucleotide	151:160	arg1	polymorphism					162:173	A non-synonymous single nucleotide polymorphism	127:173	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser)	127:298	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	6	74	theme	decreased	1144:1152	arg1	colocalization					1154:1167	decreased colocalization	1144:1167	decreased colocalization with the early endosome	1144:1191	Further, both the Cys23 and Ser23 5-HT2CR are present in the recycling pathway with the Ser23 variant having decreased colocalization with the early endosome versus the Cys23 allele.
31723224	4	75	theme	Biochemical	710:720	arg1	analyses					722:729	Biochemical analyses	710:729	Biochemical analyses	710:729	Biochemical analyses demonstrated lower Ser23 5-HT2CR plasma membrane localization versus the Cys23 5-HT2CR.
31723224	0	76	theme	Receptor	82:89	arg1	Function					91:98	Receptor Function	82:98	Receptor Function	82:98	Serotonin 5-HT2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.
31723224	8	77	theme	distinct	1377:1384	arg1	profile					1431:1437	a distinct pharmacological and subcellular localization profile	1375:1437	a distinct pharmacological and subcellular localization profile	1375:1437	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	8	78	theme	wild-type	1450:1458	arg1	allele					1466:1471	the wild-type Cys23 allele	1446:1471	the wild-type Cys23 allele	1446:1471	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	8	79	theme	Cys23Ser	1556:1563	arg1	SNP					1565:1567	the Cys23Ser SNP	1552:1567	the Cys23Ser SNP	1552:1567	Taken together, the Ser23 variant exhibits a distinct pharmacological and subcellular localization profile versus the wild-type Cys23 allele, which could impact aspects of receptor pharmacology in individuals expressing the Cys23Ser SNP.
31723224	5	80	theme	Ser23	895:899	arg1	variant					901:907	the Ser23 variant	891:907	the Ser23 variant	891:907	Subcellular localization studies demonstrated O-linked glycosylation of the Ser23 variant, but not the wild-type Cys23, may be a post-translational mechanism which alters its localization within the Golgi apparatus.
31723224	1	81	theme	impact	311:316	arg1	pharmacology					326:337	impact 5-HT2CR pharmacology	311:337	impact 5-HT2CR pharmacology	311:337	A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT2C receptor (5-HT2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT2CR pharmacology at a cellular and systems level.
31723224	2	82	theme	5-HT2CR	413:419	arg1	signaling					435:443	5-HT2CR intracellular signaling	413:443	5-HT2CR intracellular signaling	413:443	We hypothesized that the Cys23Ser alters 5-HT2CR intracellular signaling via changes in subcellular localization in vitro.
31723224	7	83	theme	Ser23	1252:1256	arg1	variant					1258:1264	the Ser23 variant	1248:1264	the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele	1248:1329	Agonism of the 5-HT2CR causes the Ser23 variant to exit the recycling pathway with no effect on the Cys23 allele.
30429311	1	0	theme	non-associative	154:168	arg1	learning					170:177	non-associative learning	154:177	non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue	154:303	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	0	1	theme	interval-dependent	60:77	arg1	habituation					79:89	interstimulus interval-dependent habituation	46:89	interstimulus interval-dependent habituation in Caenorhabditis elegans	46:115	Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.
30429311	5	2	dep	kinases	901:907	arg1	CMK-1					918:922	CMK-1	918:922	CMK-1	918:922	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	2	dep	kinases	901:907	arg1	CaMK1/4					909:915	CaMK1/4	909:915	CaMK1/4	909:915	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	2	dep	kinases	901:907	arg1	transferase					968:978	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	2	dep	kinases	901:907	arg1	kinases					901:907	Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	875:1027	Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	875:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	3	3	theme	interstimulus	533:545	arg1	interval					547:554	interstimulus interval	533:554	interstimulus interval	533:554	The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown.
30429311	6	4	dep	responses	1222:1230	arg1	i.e.					1195:1198	i.e.	1195:1198	i.e.	1195:1198	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	0	5	theme	Caenorhabditis	94:107	arg1	elegans					109:115	Caenorhabditis elegans	94:115	Caenorhabditis elegans	94:115	Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.
30429311	7	6	theme	first	1397:1401	arg1	insights					1403:1410	the first insights	1393:1410	the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates	1393:1575	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	3	7	theme	-dependent	561:570	arg1	characteristic					572:585	this interstimulus interval (ISI)-dependent characteristic	528:585	this interstimulus interval (ISI)-dependent characteristic of habituation	528:600	The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown.
30429311	3	8	theme	habituation	590:600	arg1	characteristic					572:585	this interstimulus interval (ISI)-dependent characteristic	528:585	this interstimulus interval (ISI)-dependent characteristic of habituation	528:600	The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown.
30429311	1	9	theme	sensory	269:275	arg1	adaptation					277:286	sensory adaptation	269:286	sensory adaptation	269:286	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	5	10	theme	primary	1005:1011	arg1	neurons					1021:1027	primary sensory neurons	1005:1027	primary sensory neurons	1005:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	2	11	theme	characteristics	326:340	arg1	characteristics					326:340	the defining characteristics	313:340	the defining characteristics of habituation	313:355	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	2	11	theme	characteristics	326:340	arg1	One					306:308	One	306:308	One	306:308	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	7	12	theme	different	1561:1569	arg1	rates					1571:1575	different rates	1561:1575	different rates	1561:1575	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	5	13	dep	Caenorhabditis	837:850	arg1	elegans					852:858	elegans	852:858	elegans	852:858	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	14	from	transferase	968:978	arg1	neurons					1021:1027	primary sensory neurons	1005:1027	primary sensory neurons	1005:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	7	15	theme	different	1510:1518	arg1	properties					1520:1529	different properties	1510:1529	different properties	1510:1529	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	2	16	theme	training	397:404	arg1	presented-animals					418:434	presented-animals	418:434	presented-animals habituate faster in response to more rapid stimulation	418:489	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	2	16	theme	training	397:404	arg1	stimuli					406:412	training stimuli	397:412	training stimuli	397:412	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	7	17	dep	phenomenon	1478:1487	arg1	has					1506:1508	has	1506:1508	has different properties when stimuli are delivered at different rates	1506:1575	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	5	18	theme	short	1055:1059	arg1	ISIs					1061:1064	short ISIs	1055:1064	short ISIs	1055:1064	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	19	theme	N-acetylglucosamine	937:955	arg1	transferase					968:978	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	19	theme	N-acetylglucosamine	937:955	arg1	kinases					901:907	Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	875:1027	Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	875:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	7	20	theme	conserved	1282:1290	arg1	genes					1292:1296	two conserved genes	1278:1296	two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates	1278:1575	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	5	21	link	O-linked	928:935	arg1	N-acetylglucosamine					937:955	O-linked N-acetylglucosamine	928:955	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	21	link	O-linked	928:935	arg1	O-GlcNAc					958:965	O-GlcNAc	958:965	O-GlcNAc	958:965	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	2	22	theme	defining	317:324	arg1	characteristics					326:340	the defining characteristics	313:340	the defining characteristics of habituation	313:355	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	4	23	theme	Caenorhabiditis	710:724	arg1	elegans					726:732	the nematode Caenorhabiditis elegans	697:732	the nematode Caenorhabiditis elegans	697:732	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	5	24	theme	sensory	1013:1019	arg1	neurons					1021:1027	primary sensory neurons	1005:1027	primary sensory neurons	1005:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	4	25	from	analyses	685:692	arg1	elegans					726:732	the nematode Caenorhabiditis elegans	697:732	the nematode Caenorhabiditis elegans	697:732	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	4	26	theme	nematode	701:708	arg1	elegans					726:732	the nematode Caenorhabiditis elegans	697:732	the nematode Caenorhabiditis elegans	697:732	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	5	27	theme	Ca2+/calmodulin-dependent	875:899	arg1	CMK-1					918:922	CMK-1	918:922	CMK-1	918:922	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	27	theme	Ca2+/calmodulin-dependent	875:899	arg1	CaMK1/4					909:915	CaMK1/4	909:915	CaMK1/4	909:915	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	27	theme	Ca2+/calmodulin-dependent	875:899	arg1	transferase					968:978	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	27	theme	Ca2+/calmodulin-dependent	875:899	arg1	kinases					901:907	Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	875:1027	Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	875:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	1	28	theme	motor	291:295	arg1	fatigue					297:303	motor fatigue	291:303	motor fatigue	291:303	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	6	29	theme	larger	1200:1205	arg1	responses					1222:1230	larger mechanosensory responses	1200:1230	larger mechanosensory responses than wild-type	1200:1245	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	4	30	theme	ISI-dependent	798:810	arg1	manner					812:817	an ISI-dependent manner	795:817	an ISI-dependent manner	795:817	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	6	31	theme	ogt-1	1123:1127	arg1	mutants					1129:1135	both cmk-1 and ogt-1 mutants	1108:1135	both cmk-1 and ogt-1 mutants	1108:1135	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	5	32	theme	kinases	901:907	arg1	orthologues					860:870	the Caenorhabditis elegans orthologues	833:870	the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	833:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	7	33	contain	has	1506:1508	arg1	habituation					1494:1504	habituation	1494:1504	habituation	1494:1504	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	7	33	contain	has	1506:1508	arg2	properties					1520:1529	different properties	1510:1529	different properties	1510:1529	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	6	34	dep	phenotype	1184:1192	arg1	responses					1222:1230	larger mechanosensory responses	1200:1230	larger mechanosensory responses than wild-type	1200:1245	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	0	35	from	habituation	79:89	arg1	elegans					109:115	Caenorhabditis elegans	94:115	Caenorhabditis elegans	94:115	Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.
30429311	1	36	theme	learning	170:177	arg1	Habituation					118:128	Habituation	118:128	Habituation	118:128	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	1	36	theme	learning	170:177	arg1	form					146:149	a ubiquitous form	133:149	a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue	133:303	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	4	37	theme	neurogenetic	654:665	arg1	analyses					685:692	behavioural neurogenetic and bioinformatic analyses	642:692	behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans	642:732	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	0	38	theme	CMK-1	27:31	arg1	roles					18:22	the roles	14:22	the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans	14:115	Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.
30429311	4	39	theme	first	750:754	arg1	molecules					756:764	the first molecules	746:764	the first molecules that modulate habituation in an ISI-dependent manner	746:817	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	7	40	theme	ISI-dependent	1361:1373	arg1	manner					1375:1380	an ISI-dependent manner	1358:1380	an ISI-dependent manner	1358:1380	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	7	41	theme	sensory	1315:1321	arg1	neurons					1323:1329	sensory neurons	1315:1329	sensory neurons	1315:1329	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	6	42	theme	cmk-1	1113:1117	arg1	mutants					1129:1135	both cmk-1 and ogt-1 mutants	1108:1135	both cmk-1 and ogt-1 mutants	1108:1135	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	5	43	theme	O-linked	928:935	arg1	N-acetylglucosamine					937:955	O-linked N-acetylglucosamine	928:955	O-linked N-acetylglucosamine (O-GlcNAc) transferase	928:978	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	43	theme	O-linked	928:935	arg1	O-GlcNAc					958:965	O-GlcNAc	958:965	O-GlcNAc	958:965	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	44	theme	long	1084:1087	arg1	ISIs					1089:1092	long ISIs	1084:1092	long ISIs	1084:1092	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	45	from	CMK-1	918:922	arg1	neurons					1021:1027	primary sensory neurons	1005:1027	primary sensory neurons	1005:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	1	46	theme	repeated	220:227	arg1	stimulation					229:239	repeated stimulation	220:239	repeated stimulation that cannot be explained by sensory adaptation or motor fatigue	220:303	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	2	47	theme	rapid	473:477	arg1	stimulation					479:489	more rapid stimulation	468:489	more rapid stimulation	468:489	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	2	48	from	rate	383:386	arg1	presented-animals					418:434	presented-animals	418:434	presented-animals habituate faster in response to more rapid stimulation	418:489	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	2	48	from	rate	383:386	arg1	stimuli					406:412	training stimuli	397:412	training stimuli	397:412	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	2	49	dep	presented-animals	418:434	arg1	habituate					436:444	habituate	436:444	habituate faster in response to more rapid stimulation	436:489	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	5	50	from	CaMK1/4	909:915	arg1	neurons					1021:1027	primary sensory neurons	1005:1027	primary sensory neurons	1005:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	2	51	theme	habituation	345:355	arg1	characteristics					326:340	the defining characteristics	313:340	the defining characteristics of habituation	313:355	One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation.
30429311	5	52	theme	Caenorhabditis	837:850	arg1	orthologues					860:870	the Caenorhabditis elegans orthologues	833:870	the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons	833:1027	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	5	53	dep	transferase	968:978	arg1	both					988:991	both	988:991	both	988:991	We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs.
30429311	7	54	theme	observed	1469:1476	arg1	phenomenon					1478:1487	the universally observed phenomenon	1453:1487	the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates	1453:1575	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	3	55	dep	-dependent	561:570	arg1	interval					547:554	interstimulus interval	533:554	interstimulus interval	533:554	The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown.
30429311	6	56	theme	mechanosensory	1207:1220	arg1	responses					1222:1230	larger mechanosensory responses	1200:1230	larger mechanosensory responses than wild-type	1200:1245	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	7	57	theme	molecular	1421:1429	arg1	mechanisms					1431:1440	the molecular mechanisms	1417:1440	the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates	1417:1575	Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.
30429311	1	58	theme	ubiquitous	135:144	arg1	Habituation					118:128	Habituation	118:128	Habituation	118:128	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	1	58	theme	ubiquitous	135:144	arg1	form					146:149	a ubiquitous form	133:149	a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue	133:303	Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue.
30429311	0	59	theme	interstimulus	46:58	arg1	habituation					79:89	interstimulus interval-dependent habituation	46:89	interstimulus interval-dependent habituation in Caenorhabditis elegans	46:115	Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.
30429311	4	60	theme	bioinformatic	671:683	arg1	analyses					685:692	behavioural neurogenetic and bioinformatic analyses	642:692	behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans	642:732	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	6	61	theme	mechanosensory	1152:1165	arg1	phenotype					1184:1192	a rare mechanosensory hyper-responsive phenotype	1145:1192	a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type)	1145:1246	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	3	62	theme	molecular	496:504	arg1	mechanisms					506:515	The molecular mechanisms	492:515	The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation	492:600	The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown.
30429311	4	63	theme	behavioural	642:652	arg1	analyses					685:692	behavioural neurogenetic and bioinformatic analyses	642:692	behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans	642:732	In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner.
30429311	0	64	theme	OGT-1	37:41	arg1	roles					18:22	the roles	14:22	the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans	14:115	Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.
30429311	0	65	from	roles	18:22	arg1	habituation					79:89	interstimulus interval-dependent habituation	46:89	interstimulus interval-dependent habituation in Caenorhabditis elegans	46:115	Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.
30429311	6	66	theme	hyper-responsive	1167:1182	arg1	phenotype					1184:1192	a rare mechanosensory hyper-responsive phenotype	1145:1192	a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type)	1145:1246	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30429311	6	67	theme	rare	1147:1150	arg1	phenotype					1184:1192	a rare mechanosensory hyper-responsive phenotype	1145:1192	a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type)	1145:1246	In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).
30487280	9	0	theme	viruses.IMPORTANCE	1724:1741	arg1	neutralization					1686:1699	increased neutralization	1676:1699	increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells	1676:1879	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	6	1	theme	glycan	1152:1157	arg1	holes					1159:1163	glycan holes	1152:1163	glycan holes	1152:1163	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	7	2	theme	NAb	1328:1330	arg1	epitope					1332:1338	the sole autologous NAb epitope	1308:1338	the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer	1308:1367	We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer.
30487280	9	3	theme	SOSIP	1754:1758	arg1	trimers					1760:1766	SOSIP trimers	1754:1766	SOSIP trimers	1754:1766	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	11	4	from	epitopes	2043:2050	arg1	holes					2055:2059	holes	2055:2059	holes	2055:2059	These neutralizing antibodies recognize epitopes in holes in the glycan shield that covers the trimer.
30487280	7	5	theme	sole	1312:1315	arg1	epitope					1332:1338	the sole autologous NAb epitope	1308:1338	the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer	1308:1367	We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer.
30487280	6	6	theme	strongest	1046:1054	arg1	evidence					1056:1063	The strongest evidence	1042:1063	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes,	1042:1164	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	3	7	theme	glycan	646:651	arg1	absence					633:639	the absence	629:639	the absence of a glycan at residue 241	629:666	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	15	8	theme	HIV-1	2626:2630	arg1	vaccines					2632:2639	HIV-1 vaccines	2626:2639	HIV-1 vaccines based on envelope glycoproteins	2626:2671	Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.
30487280	1	9	used	used	267:270	arg2	trimers					248:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	10	10	theme	sequence-matched	1970:1985	arg1	isolates					1993:2000	resistant sequence-matched HIV-1 isolates	1960:2000	resistant sequence-matched HIV-1 isolates	1960:2000	When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched HIV-1 isolates.
30487280	9	11	from	redirection	1648:1658	arg1	study					1628:1632	neither study	1620:1632	neither study	1620:1632	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	15	12	theme	antibodies	2612:2621	arg1	induction					2578:2586	the induction	2574:2586	the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins	2574:2671	Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.
30487280	15	13	theme	antibody	2474:2481	arg1	response					2483:2490	the antibody response	2470:2490	the antibody response	2470:2490	Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.
30487280	1	14	theme	HIV-1	175:179	arg1	research					189:196	HIV-1 vaccine research	175:196	HIV-1 vaccine research	175:196	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	13	15	theme	new	2270:2272	arg1	holes					2274:2278	new holes	2270:2278	new holes that might expose new immunogenic epitopes	2270:2321	In addition, we removed selected other glycans to open new holes that might expose new immunogenic epitopes.
30487280	2	16	from	holes	447:451	arg1	shields					467:473	the glycan shields	456:473	the glycan shields that cover most of the protein surfaces	456:513	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	3	17	from	absence	633:639	arg1	residue					656:662	residue 241	656:666	residue 241	656:666	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	0	18	theme	Antibody	122:129	arg1	Response					131:138	the Neutralizing Antibody Response	105:138	the Neutralizing Antibody Response to the Newly Unmasked Epitopes	105:169	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	3	19	theme	autologous	548:557	arg1	epitope					563:569	the dominant autologous NAb epitope	535:569	the dominant autologous NAb epitope in rabbits	535:580	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	1	20	theme	native-like	199:209	arg1	trimers					248:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	7	21	from	epitope	1332:1338	arg1	trimer					1362:1367	the B41 SOSIP.v4.1 trimer	1343:1367	the B41 SOSIP.v4.1 trimer	1343:1367	We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer.
30487280	4	22	link	N-linked	754:761	arg1	glycan					763:768	an N-linked glycan	751:768	an N-linked glycan	751:768	Here, we blocked this epitope in BG505 SOSIPv4.1 trimer immunogens by knocking in an N-linked glycan at residue 241.
30487280	6	23	theme	NAb	1088:1090	arg1	response					1092:1099	the NAb response	1084:1099	the NAb response to neoepitopes, through the opening and closing of glycan holes,	1084:1164	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	9	24	theme	particles	1836:1844	arg1	surface					1819:1825	the surface	1815:1825	the surface of HIV-1 particles	1815:1844	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	2	25	theme	glycan	460:465	arg1	shields					467:473	the glycan shields	456:473	the glycan shields that cover most of the protein surfaces	456:513	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	6	26	theme	site	1247:1250	arg1	occupancy					1225:1233	the highest occupancy	1213:1233	the highest occupancy of the N241 site	1213:1250	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	10	27	theme	test	1907:1910	arg1	animals					1912:1918	test animals	1907:1918	test animals	1907:1918	When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched HIV-1 isolates.
30487280	0	28	theme	Envelope	56:63	arg1	Glycoprotein					65:76	HIV-1 Envelope Glycoprotein	50:76	HIV-1 Envelope Glycoprotein SOSIP Trimers	50:90	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	14	29	theme	responses	2439:2447	arg1	specificities					2409:2421	the specificities	2405:2421	the specificities of the antibody responses	2405:2447	We immunized rabbits with the various glycan-modified trimers and then dissected the specificities of the antibody responses.
30487280	0	30	from	Closing	0:6	arg1	Shield					40:45	Shield	40:45	Shield	40:45	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	0	31	theme	SOSIP	78:82	arg1	Trimers					84:90	HIV-1 Envelope Glycoprotein SOSIP Trimers	50:90	HIV-1 Envelope Glycoprotein SOSIP Trimers	50:90	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	5	32	theme	241-glycan-bearing	955:972	arg1	trimers					980:986	the 241-glycan-bearing BG505 trimers	951:986	the 241-glycan-bearing BG505 trimers	951:986	We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites.
30487280	1	33	gly	glycoprotein	229:240	arg1	glycoprotein					229:240	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	3	34	from	epitope	563:569	arg1	rabbits					574:580	rabbits	574:580	rabbits	574:580	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	2	35	theme	B41	379:381	arg1	trimers					389:395	B41 SOSIP trimers	379:395	B41 SOSIP trimers	379:395	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	13	36	theme	immunogenic	2302:2312	arg1	epitopes					2314:2321	new immunogenic epitopes	2298:2321	new immunogenic epitopes	2298:2321	In addition, we removed selected other glycans to open new holes that might expose new immunogenic epitopes.
30487280	12	37	from	epitopes	2174:2181	arg1	trimers					2206:2212	B41 SOSIP trimers	2196:2212	B41 SOSIP trimers	2196:2212	Here, we added glycans to block the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers.
30487280	12	37	from	epitopes	2174:2181	arg1	BG505					2186:2190	BG505	2186:2190	BG505	2186:2190	Here, we added glycans to block the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers.
30487280	5	38	theme	single	847:852	arg1	glycans					863:869	single N-linked glycans	847:869	single N-linked glycans	847:869	We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites.
30487280	13	39	theme	selected	2239:2246	arg1	glycans					2254:2260	selected other glycans	2239:2260	selected other glycans	2239:2260	In addition, we removed selected other glycans to open new holes that might expose new immunogenic epitopes.
30487280	0	40	theme	Opening	12:18	arg1	Holes					20:24	Opening Holes	12:24	Opening Holes	12:24	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	1	41	theme	immunizing	276:285	arg1	animals					287:293	immunizing animals	276:293	immunizing animals	276:293	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	15	42	theme	envelope	2650:2657	arg1	glycoproteins					2659:2671	envelope glycoproteins	2650:2671	envelope glycoproteins	2650:2671	Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.
30487280	2	43	theme	few	443:445	arg1	holes					447:451	a few holes	441:451	a few holes in the glycan shields that cover most of the protein surfaces	441:513	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	13	44	theme	other	2248:2252	arg1	glycans					2254:2260	selected other glycans	2239:2260	selected other glycans	2239:2260	In addition, we removed selected other glycans to open new holes that might expose new immunogenic epitopes.
30487280	2	45	from	BG505	369:373	arg1	macaques					412:419	macaques	412:419	macaques	412:419	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	2	45	from	BG505	369:373	arg1	rabbits					400:406	rabbits	400:406	rabbits	400:406	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	8	46	theme	new	1420:1422	arg1	site					1436:1439	the new N289-glycan site	1416:1439	the new N289-glycan site	1416:1439	Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out.
30487280	12	47	theme	immunogenic	2147:2157	arg1	epitopes					2174:2181	the most immunogenic neutralization epitopes	2138:2181	the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers	2138:2212	Here, we added glycans to block the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers.
30487280	7	48	theme	SOSIP.v4.1	1351:1360	arg1	trimer					1362:1367	the B41 SOSIP.v4.1 trimer	1343:1367	the B41 SOSIP.v4.1 trimer	1343:1367	We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer.
30487280	4	49	theme	SOSIPv4.1	708:716	arg1	immunogens					725:734	BG505 SOSIPv4.1 trimer immunogens	702:734	BG505 SOSIPv4.1 trimer immunogens	702:734	Here, we blocked this epitope in BG505 SOSIPv4.1 trimer immunogens by knocking in an N-linked glycan at residue 241.
30487280	2	50	theme	neutralizing	323:334	arg1	antibodies					336:345	autologous neutralizing antibodies	312:345	autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques	312:419	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	2	50	theme	neutralizing	323:334	arg1	NAbs					348:351	NAbs	348:351	NAbs	348:351	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	2	51	from	trimers	389:395	arg1	macaques					412:419	macaques	412:419	macaques	412:419	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	2	51	from	trimers	389:395	arg1	rabbits					400:406	rabbits	400:406	rabbits	400:406	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	9	52	theme	heterologous	1704:1715	arg1	viruses.IMPORTANCE					1724:1741	heterologous tier 2 viruses.IMPORTANCE	1704:1741	heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells	1704:1879	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	10	53	theme	HIV-1	1987:1991	arg1	isolates					1993:2000	resistant sequence-matched HIV-1 isolates	1960:2000	resistant sequence-matched HIV-1 isolates	1960:2000	When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched HIV-1 isolates.
30487280	1	54	theme	envelope	220:227	arg1	trimers					248:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	14	55	theme	various	2354:2360	arg1	trimers					2378:2384	the various glycan-modified trimers	2350:2384	the various glycan-modified trimers	2350:2384	We immunized rabbits with the various glycan-modified trimers and then dissected the specificities of the antibody responses.
30487280	10	56	theme	resistant	1960:1968	arg1	isolates					1993:2000	resistant sequence-matched HIV-1 isolates	1960:2000	resistant sequence-matched HIV-1 isolates	1960:2000	When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched HIV-1 isolates.
30487280	6	57	theme	N241	1242:1245	arg1	site					1247:1250	the N241 site	1238:1250	the N241 site	1238:1250	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	6	58	theme	holes	1159:1163	arg1	opening					1129:1135	opening	1129:1135	opening	1129:1135	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	6	58	theme	holes	1159:1163	arg1	closing					1141:1147	closing	1141:1147	closing	1141:1147	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	8	59	theme	response	1524:1531	arg1	redirection					1501:1511	redirection	1501:1511	redirection of the NAb response to a neoepitope when this site was knocked in	1501:1577	Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out.
30487280	1	60	theme	SOSIP	242:246	arg1	trimers					248:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	6	61	dep	opening	1129:1135	arg1	the					1125:1127	the	1125:1127	the	1125:1127	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	7	62	theme	autologous	1317:1326	arg1	epitope					1332:1338	the sole autologous NAb epitope	1308:1338	the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer	1308:1367	We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer.
30487280	9	63	theme	increased	1676:1684	arg1	neutralization					1686:1699	increased neutralization	1676:1699	increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells	1676:1879	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	4	64	theme	N-linked	754:761	arg1	glycan					763:768	an N-linked glycan	751:768	an N-linked glycan	751:768	Here, we blocked this epitope in BG505 SOSIPv4.1 trimer immunogens by knocking in an N-linked glycan at residue 241.
30487280	9	65	theme	envelope-glycoprotein	1774:1794	arg1	spikes					1796:1801	envelope-glycoprotein spikes	1774:1801	envelope-glycoprotein spikes	1774:1801	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	15	66	theme	cross-reactive	2534:2547	arg1	one					2549:2551	a more cross-reactive one	2527:2551	a more cross-reactive one	2527:2551	Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.
30487280	15	67	theme	neutralizing	2599:2610	arg1	antibodies					2612:2621	broadly neutralizing antibodies	2591:2621	broadly neutralizing antibodies	2591:2621	Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.
30487280	3	68	theme	BG505	520:524	arg1	trimers					526:532	BG505 trimers	520:532	BG505 trimers	520:532	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	6	69	with	groups	1201:1206	arg1	occupancy					1225:1233	the highest occupancy	1213:1233	the highest occupancy of the N241 site	1213:1250	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	11	70	theme	neutralizing	2009:2020	arg1	antibodies					2022:2031	These neutralizing antibodies	2003:2031	These neutralizing antibodies	2003:2031	These neutralizing antibodies recognize epitopes in holes in the glycan shield that covers the trimer.
30487280	3	71	from	residue	656:662	arg1	absence					633:639	the absence	629:639	the absence of a glycan at residue 241	629:666	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	3	71	from	residue	656:662	arg1	glycan					646:651	a glycan	644:651	a glycan at residue 241	644:666	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	0	72	theme	Neutralizing	109:120	arg1	Response					131:138	the Neutralizing Antibody Response	105:138	the Neutralizing Antibody Response to the Newly Unmasked Epitopes	105:169	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	1	73	theme	vaccine	181:187	arg1	research					189:196	HIV-1 vaccine research	175:196	HIV-1 vaccine research	175:196	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	2	74	theme	protein	498:504	arg1	surfaces					506:513	the protein surfaces	494:513	the protein surfaces	494:513	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	6	75	theme	immunogen	1191:1199	arg1	groups					1201:1206	trimer immunogen groups	1184:1206	trimer immunogen groups with the highest occupancy of the N241 site	1184:1250	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	3	76	theme	dominant	539:546	arg1	epitope					563:569	the dominant autologous NAb epitope	535:569	the dominant autologous NAb epitope in rabbits	535:580	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	12	77	theme	neutralization	2159:2172	arg1	epitopes					2174:2181	the most immunogenic neutralization epitopes	2138:2181	the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers	2138:2212	Here, we added glycans to block the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers.
30487280	8	78	theme	N356-glycan	1587:1597	arg1	site					1599:1602	the N356-glycan site	1583:1602	the N356-glycan site	1583:1602	Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out.
30487280	8	79	dep	found	1477:1481	arg1	knocked					1604:1610	knocked	1604:1610	found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out	1477:1614	Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out.
30487280	6	80	theme	response	1092:1099	arg1	redirection					1069:1079	redirection	1069:1079	redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes,	1069:1164	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	9	81	theme	HIV-1	1830:1834	arg1	particles					1836:1844	HIV-1 particles	1830:1844	HIV-1 particles	1830:1844	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	0	82	theme	Unmasked	153:160	arg1	Epitopes					162:169	the Newly Unmasked Epitopes	143:169	the Newly Unmasked Epitopes	143:169	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	2	83	dep	BG505	369:373	arg1	the					365:367	the	365:367	the	365:367	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	12	84	theme	B41	2196:2198	arg1	trimers					2206:2212	B41 SOSIP trimers	2196:2212	B41 SOSIP trimers	2196:2212	Here, we added glycans to block the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers.
30487280	15	85	gly	glycoproteins	2659:2671	arg1	glycoproteins					2659:2671	envelope glycoproteins	2650:2671	envelope glycoproteins	2650:2671	Thus, in principle, the antibody response might be diverted from one site to a more cross-reactive one, which would help in the induction of broadly neutralizing antibodies by HIV-1 vaccines based on envelope glycoproteins.
30487280	0	86	theme	HIV-1	50:54	arg1	Glycoprotein					65:76	HIV-1 Envelope Glycoprotein	50:76	HIV-1 Envelope Glycoprotein SOSIP Trimers	50:90	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	5	87	theme	NAb	926:928	arg1	responses					930:938	NAb responses	926:938	NAb responses induced by the 241-glycan-bearing BG505 trimers	926:986	We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites.
30487280	3	88	theme	NAb	559:561	arg1	epitope					563:569	the dominant autologous NAb epitope	535:569	the dominant autologous NAb epitope in rabbits	535:580	For BG505 trimers, the dominant autologous NAb epitope in rabbits involves residues that line a cavity caused by the absence of a glycan at residue 241.
30487280	0	89	from	Holes	20:24	arg1	Shield					40:45	Shield	40:45	Shield	40:45	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	9	90	theme	viral	1858:1862	arg1	entry					1864:1868	viral entry	1858:1868	viral entry into cells	1858:1879	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	0	91	theme	Glycoprotein	65:76	arg1	Trimers					84:90	HIV-1 Envelope Glycoprotein SOSIP Trimers	50:90	HIV-1 Envelope Glycoprotein SOSIP Trimers	50:90	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	0	92	theme	Trimers	84:90	arg1	Shield					40:45	Shield	40:45	Shield	40:45	Closing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked Epitopes.
30487280	1	93	dep	native-like	199:209	arg1	soluble					212:218	soluble	212:218	soluble	212:218	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30487280	14	94	theme	antibody	2430:2437	arg1	responses					2439:2447	the antibody responses	2426:2447	the antibody responses	2426:2447	We immunized rabbits with the various glycan-modified trimers and then dissected the specificities of the antibody responses.
30487280	6	95	theme	highest	1217:1223	arg1	occupancy					1225:1233	the highest occupancy	1213:1233	the highest occupancy of the N241 site	1213:1250	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	5	96	theme	BG505	974:978	arg1	trimers					980:986	the 241-glycan-bearing BG505 trimers	951:986	the 241-glycan-bearing BG505 trimers	951:986	We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites.
30487280	13	97	theme	new	2298:2300	arg1	epitopes					2314:2321	new immunogenic epitopes	2298:2321	new immunogenic epitopes	2298:2321	In addition, we removed selected other glycans to open new holes that might expose new immunogenic epitopes.
30487280	8	98	theme	retrospective	1381:1393	arg1	analysis					1395:1402	a retrospective analysis	1379:1402	a retrospective analysis	1379:1402	Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out.
30487280	14	99	theme	glycan-modified	2362:2376	arg1	trimers					2378:2384	the various glycan-modified trimers	2350:2384	the various glycan-modified trimers	2350:2384	We immunized rabbits with the various glycan-modified trimers and then dissected the specificities of the antibody responses.
30487280	12	100	theme	SOSIP	2200:2204	arg1	trimers					2206:2212	B41 SOSIP trimers	2196:2212	B41 SOSIP trimers	2196:2212	Here, we added glycans to block the most immunogenic neutralization epitopes on BG505 and B41 SOSIP trimers.
30487280	5	101	theme	N-linked	854:861	arg1	glycans					863:869	single N-linked glycans	847:869	single N-linked glycans	847:869	We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites.
30487280	6	102	gly	occupancy	1225:1233	arg2	site					1247:1250	the N241 site	1238:1250	the N241 site	1238:1250	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	8	103	theme	N289-glycan	1424:1434	arg1	site					1436:1439	the new N289-glycan site	1416:1439	the new N289-glycan site	1416:1439	Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out.
30487280	2	104	theme	SOSIP	383:387	arg1	trimers					389:395	B41 SOSIP trimers	379:395	B41 SOSIP trimers	379:395	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	5	105	theme	opened	1028:1033	arg1	sites					1035:1039	the newly opened sites	1018:1039	the newly opened sites	1018:1039	We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites.
30487280	9	106	gly	envelope-glycoprotein	1774:1794	arg1	envelope-glycoprotein					1774:1794	envelope-glycoprotein spikes	1774:1801	envelope-glycoprotein spikes	1774:1801	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	2	107	theme	antibodies	336:345	arg1	epitopes					300:307	The epitopes	296:307	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques	296:419	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	6	108	theme	trimer	1184:1189	arg1	groups					1201:1206	trimer immunogen groups	1184:1206	trimer immunogen groups with the highest occupancy of the N241 site	1184:1250	The strongest evidence for redirection of the NAb response to neoepitopes, through the opening and closing of glycan holes, was obtained from trimer immunogen groups with the highest occupancy of the N241 site.
30487280	4	109	theme	BG505	702:706	arg1	immunogens					725:734	BG505 SOSIPv4.1 trimer immunogens	702:734	BG505 SOSIPv4.1 trimer immunogens	702:734	Here, we blocked this epitope in BG505 SOSIPv4.1 trimer immunogens by knocking in an N-linked glycan at residue 241.
30487280	2	110	theme	autologous	312:321	arg1	antibodies					336:345	autologous neutralizing antibodies	312:345	autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques	312:419	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	2	110	theme	autologous	312:321	arg1	NAbs					348:351	NAbs	348:351	NAbs	348:351	The epitopes of autologous neutralizing antibodies (NAbs) induced by the BG505 and B41 SOSIP trimers in rabbits and macaques have been mapped to a few holes in the glycan shields that cover most of the protein surfaces.
30487280	8	111	theme	NAb	1520:1522	arg1	response					1524:1531	the NAb response	1516:1531	the NAb response	1516:1531	Although a retrospective analysis showed that the new N289-glycan site was substantially underoccupied, we found some evidence for redirection of the NAb response to a neoepitope when this site was knocked in and the N356-glycan site knocked out.
30487280	5	112	link	N-linked	854:861	arg1	glycans					863:869	single N-linked glycans	847:869	single N-linked glycans	847:869	We then opened holes elsewhere on the trimer by knocking out single N-linked glycans at residues 197, 234, 276, 332, and 355 and found that NAb responses induced by the 241-glycan-bearing BG505 trimers were frequently redirected to the newly opened sites.
30487280	7	113	theme	B41	1347:1349	arg1	trimer					1362:1367	the B41 SOSIP.v4.1 trimer	1343:1367	the B41 SOSIP.v4.1 trimer	1343:1367	We also attempted to knock in the N289-glycan to block the sole autologous NAb epitope on the B41 SOSIP.v4.1 trimer.
30487280	9	114	theme	tier	1717:1720	arg1	viruses.IMPORTANCE					1724:1741	heterologous tier 2 viruses.IMPORTANCE	1704:1741	heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells	1704:1879	In neither study, however, was redirection associated with increased neutralization of heterologous tier 2 viruses.IMPORTANCE Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells.
30487280	4	115	theme	trimer	718:723	arg1	immunogens					725:734	BG505 SOSIPv4.1 trimer immunogens	702:734	BG505 SOSIPv4.1 trimer immunogens	702:734	Here, we blocked this epitope in BG505 SOSIPv4.1 trimer immunogens by knocking in an N-linked glycan at residue 241.
30487280	1	116	theme	glycoprotein	229:240	arg1	trimers					248:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	native-like, soluble envelope glycoprotein SOSIP trimers	199:254	In HIV-1 vaccine research, native-like, soluble envelope glycoprotein SOSIP trimers are widely used for immunizing animals.
30392210	11	0	theme	NAFLD	1849:1853	arg1	group					1855:1859	the NAFLD group	1845:1859	the NAFLD group	1845:1859	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	6	1	theme	low-density	956:966	arg1	lipoprotein					968:978	low-density lipoprotein	956:978	low-density lipoprotein	956:978	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	13	2	dep	P=0.006	2624:2630	arg1	×10					2672:2674	Bifidobacterium 19.680 (6.181, 53.944) ×10(-3)	2633:2678	×10	2672:2674	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	10	3	theme	cm	1688:1689	arg1	88.6±6.6					1663:1670	88.6±6.6	1663:1670	88.6±6.6	1663:1670	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	3	theme	cm	1688:1689	arg1	circumference					1648:1660	waist circumference	1642:1660	waist circumference (88.6±6.6)	1642:1671	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	13	4	from	group	2497:2501	arg1	lower					2522:2526	lower	2522:2526	lower	2522:2526	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	4	from	group	2497:2501	arg1	proportion					2438:2447	the proportion	2434:2447	the proportion of Bacteroides and Bifidobacterium in the NAFLD group	2434:2501	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	14	5	theme	polysaccharides	3161:3175	arg1	biosynthesis					3177:3188	polysaccharides biosynthesis	3161:3188	polysaccharides biosynthesis	3161:3188	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	4	6	theme	healthy	572:578	arg1	children					580:587	Twenty-two healthy children	561:587	Twenty-two healthy children	561:587	Twenty-two healthy children were enrolled in the control group.
30392210	13	7	dep	higher	2800:2805	arg1	P=0.035					2882:2888	P=0.035	2882:2888	P=0.035	2882:2888	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	7	dep	higher	2800:2805	arg1	Z=-2.112					2872:2879	Z=-2.112	2872:2879	Z=-2.112	2872:2879	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	7	dep	higher	2800:2805	arg1	×10					2830:2832	3.089 (0.165, 63.502) ×10(-3)	2808:2836	×10	2830:2832	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	7	dep	higher	2800:2805	arg1	×10					2863:2865	0.432 (0.029, 2.257) ×10(-3)	2842:2869	×10	2863:2865	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	1	8	theme	which	246:250	arg1	role					238:241	the role	234:241	the role of which in pathogenesis of NAFLD	234:275	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	8	theme	which	246:250	arg1	composition					121:131	composition	121:131	composition	121:131	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	8	theme	which	246:250	arg1	richness					137:144	richness	137:144	richness	137:144	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	11	9	dep	lower	1836:1840	arg1	4.63					1898:1901	4.63	1898:1901	4.63	1898:1901	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	9	dep	lower	1836:1840	arg1	4.21					1904:1907	4.21	1904:1907	4.21	1904:1907	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	9	dep	lower	1836:1840	arg1	index					1870:1874	index	1870:1874	index	1870:1874	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	13	10	from	proportion	2438:2447	arg1	group					2497:2501	the NAFLD group	2487:2501	the NAFLD group	2487:2501	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	11	11	dep	0.88	1978:1981	arg1	0.93					1984:1987	0.93	1984:1987	0.93	1984:1987	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	5	12	dep	years	709:713	arg1	males					719:723	10 males	716:723	10 males	716:723	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	5	12	dep	years	709:713	arg1	females					732:738	12 females	729:738	12 females	729:738	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	14	13	theme	acid	3141:3144	arg1	synthesis					3146:3154	fatty acid synthesis	3135:3154	fatty acid synthesis	3135:3154	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	3	14	theme	Medicine	540:547	arg1	Hospitals					510:518	the Second and First Affiliated Hospitals	478:518	the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University	478:558	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	9	15	theme	intestinal	1344:1353	arg1	characteristics					1361:1375	The intestinal flora characteristics	1340:1375	The intestinal flora characteristics between the two groups	1340:1398	The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test.
30392210	14	16	theme	differential	2961:2972	arg1	pathways					2984:2991	26 differential metabolic pathways	2958:2991	26 differential metabolic pathways	2958:2991	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	6	17	theme	waist	828:832	arg1	circumference					834:846	waist circumference	828:846	waist circumference	828:846	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	16	18	from	disturbances	3366:3377	arg1	abundance					3401:3409	abundance	3401:3409	abundance	3401:3409	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	16	18	from	disturbances	3366:3377	arg1	diversity					3387:3395	diversity	3387:3395	diversity	3387:3395	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	14	19	theme	biosynthesis	3177:3188	arg1	pathways					3090:3097	the pathways	3086:3097	the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism	3086:3203	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	4	20	theme	control	610:616	arg1	group					618:622	the control group	606:622	the control group	606:622	Twenty-two healthy children were enrolled in the control group.
30392210	5	21	theme	were	665:668	arg1	females					670:676	9 were females	663:676	9 were females	663:676	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	3	22	theme	Zhejiang	523:530	arg1	Medicine					540:547	Zhejiang Chinese Medicine University	523:558	Zhejiang Chinese Medicine University	523:558	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	5	23	theme	control	747:753	arg1	group					755:759	the control group	743:759	the control group	743:759	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	16	24	theme	lipid	3428:3432	arg1	pathways					3444:3451	lipid metabolic pathways	3428:3451	lipid metabolic pathways	3428:3451	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	1	25	from	role	238:241	arg1	children					174:181	children	174:181	children with non-alcoholic fatty liver disease (NAFLD)	174:228	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	25	from	role	238:241	arg1	pathogenesis					255:266	pathogenesis	255:266	pathogenesis of NAFLD	255:275	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	14	26	theme	expressed	2938:2946	arg1	genes					2948:2952	78 differentially expressed genes	2920:2952	78 differentially expressed genes	2920:2952	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	14	27	theme	metabolism	3123:3132	arg1	pathways					3090:3097	the pathways	3086:3097	the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism	3086:3203	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	6	28	theme	mass	807:810	arg1	BMI					819:821	BMI	819:821	BMI	819:821	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	6	28	theme	mass	807:810	arg1	index					812:816	The body mass index	798:816	The body mass index (BMI)	798:822	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	11	29	theme	intestinal	1809:1818	arg1	microflora					1820:1829	intestinal microflora	1809:1829	intestinal microflora	1809:1829	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	7	30	from	composition	1093:1103	arg1	groups					1158:1163	the two groups	1150:1163	the two groups	1150:1163	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	12	31	theme	NAFLD	2203:2207	arg1	Actinobacteri					2216:2228	Actinobacteri	2216:2228	Actinobacteri	2216:2228	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	31	theme	NAFLD	2203:2207	arg1	group					2209:2213	NAFLD group	2203:2213	NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006)	2203:2407	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	16	32	theme	intestinal	3349:3358	arg1	disturbances					3366:3377	intestinal flora disturbances	3349:3377	intestinal flora disturbances	3349:3377	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	6	33	theme	blood	879:883	arg1	glucose					885:891	the fasting blood glucose	867:891	the fasting blood glucose	867:891	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	16	34	contain	have	3344:3347	arg2	disturbances					3366:3377	intestinal flora disturbances	3349:3377	intestinal flora disturbances	3349:3377	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	16	34	contain	have	3344:3347	arg1	children					3335:3342	NAFLD children	3329:3342	NAFLD children	3329:3342	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	0	35	theme	nonalcoholic	60:71	arg1	disease					85:91	nonalcoholic fatty liver disease	60:91	nonalcoholic fatty liver disease	60:91	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	9	36	theme	t	1419:1419	arg1	test					1421:1424	t test	1419:1424	t test	1419:1424	The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test.
30392210	13	37	theme	NAFLD	2770:2774	arg1	group					2776:2780	NAFLD group	2770:2780	NAFLD group	2770:2780	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	15	38	theme	function	3227:3234	arg1	genes					3236:3240	these three function genes	3215:3240	these three function genes	3215:3240	Besides, these three function genes were related to Bacteroides, Prevotella, Bifidobacterium and Ruminococcus.
30392210	12	39	theme	Thermus	2181:2187	arg1	proportion					2167:2176	the proportion	2163:2176	the proportion of Thermus	2163:2187	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	39	theme	Thermus	2181:2187	arg1	higher					2193:2198	higher	2193:2198	higher	2193:2198	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	0	40	theme	liver	79:83	arg1	disease					85:91	nonalcoholic fatty liver disease	60:91	nonalcoholic fatty liver disease	60:91	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	5	41	from	years	709:713	arg1	males					653:657	males	653:657	males	653:657	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	5	41	from	years	709:713	arg1	females					670:676	9 were females	663:676	9 were females	663:676	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	1	42	theme	intestinal	149:158	arg1	microflora					160:169	intestinal microflora	149:169	intestinal microflora	149:169	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	10	43	dep	BMI	1586:1588	arg1	circumference					1648:1660	waist circumference	1642:1660	waist circumference (88.6±6.6)	1642:1671	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	P=0.046					1762:1768	P=0.046	1762:1768	P=0.046	1762:1768	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	triglyceride					1710:1721	triglyceride (0.9±0.4)	1710:1731	triglyceride (0.9±0.4)	1710:1731	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	88.6±6.6					1663:1670	88.6±6.6	1663:1670	88.6±6.6	1663:1670	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	kg/m					1615:1618	kg/m(2)	1615:1621	BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2)	1586:1621	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	mmol/L					1745:1750	(0.7±0.3)mmol/L	1736:1750	(0.7±0.3)mmol/L	1736:1750	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	P=0.000					1633:1639	P=0.000	1633:1639	P=0.000	1633:1639	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	t=8.520					1692:1698	t=8.520	1692:1698	t=8.520	1692:1698	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	43	dep	BMI	1586:1588	arg1	t=2.060					1753:1759	t=2.060	1753:1759	t=2.060	1753:1759	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	5	44	from	females	732:738	arg1	group					755:759	the control group	743:759	the control group	743:759	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	14	45	theme	KEGG	2905:2908	arg1	database					2910:2917	the KEGG database	2901:2917	the KEGG database	2901:2917	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	9	46	theme	U	1442:1442	arg1	test					1444:1447	Mann-Whitney U test	1429:1447	Mann-Whitney U test	1429:1447	The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test.
30392210	11	47	dep	326.96	2048:2053	arg1	275.34					2056:2061	275.34	2056:2061	275.34	2056:2061	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	8	48	theme	KO	1236:1237	arg1	enrichment					1292:1301	The KO differential gene expression and KEGG signal pathway enrichment	1232:1301	The KO differential gene expression and KEGG signal pathway enrichment	1232:1301	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	7	49	theme	beads	1074:1078	arg1	methods					1080:1086	magnetic beads methods	1065:1086	magnetic beads methods	1065:1086	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	13	50	theme	Prevotella	2756:2765	arg1	higher					2800:2805	higher	2800:2805	higher	2800:2805	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	50	theme	Prevotella	2756:2765	arg1	proportion					2742:2751	the proportion	2738:2751	the proportion of Prevotella in NAFLD group	2738:2780	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	6	51	theme	high-density	927:938	arg1	lipoprotein					940:950	high-density lipoprotein	927:950	high-density lipoprotein	927:950	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	0	52	theme	fatty	73:77	arg1	disease					85:91	nonalcoholic fatty liver disease	60:91	nonalcoholic fatty liver disease	60:91	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	8	53	theme	gene	1252:1255	arg1	expression					1257:1266	differential gene expression	1239:1266	differential gene expression	1239:1266	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	0	54	theme	[Specific	0:8	arg1	changes					10:16	[Specific changes	0:16	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease	0:91	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	9	55	theme	W	1463:1463	arg1	test					1465:1468	Willcoxon W test	1453:1468	Willcoxon W test	1453:1468	The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test.
30392210	14	56	theme	K01961	3047:3052	arg1	genes					3030:3034	the function genes	3017:3034	the function genes of K01470, K01961 and K07258	3017:3063	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	7	57	theme	high	1193:1196	arg1	sequencing					1209:1218	16S rDNA high throughput sequencing	1184:1218	16S rDNA high throughput sequencing technology	1184:1229	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	11	58	dep	4.21	1904:1907	arg1	4.81					1910:1913	4.81	1910:1913	4.81	1910:1913	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	59	theme	ACE	2010:2012	arg1	index					2014:2018	ACE index 235.76 (205.26, 361.94)	2010:2042	index	2014:2018	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	5	60	from	age	774:776	arg1	males					653:657	males	653:657	males	653:657	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	5	60	from	age	774:776	arg1	females					670:676	9 were females	663:676	9 were females	663:676	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	14	61	theme	K01470	3039:3044	arg1	genes					3030:3034	the function genes	3017:3034	the function genes of K01470, K01961 and K07258	3017:3063	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	7	62	theme	16S	1184:1186	arg1	sequencing					1209:1218	16S rDNA high throughput sequencing	1184:1218	16S rDNA high throughput sequencing technology	1184:1229	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	8	63	theme	signal	1277:1282	arg1	pathway					1284:1290	KEGG signal pathway	1272:1290	KEGG signal pathway	1272:1290	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	7	64	theme	fecal	1024:1028	arg1	microorganisms					1030:1043	the fecal microorganisms	1020:1043	the fecal microorganisms	1020:1043	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	0	65	theme	microflora	32:41	arg1	changes					10:16	[Specific changes	0:16	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease	0:91	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	2	66	theme	case-control	310:321	arg1	Methods					278:284	Methods	278:284	Methods: This was a prospective case-control study.	278:328	Methods: This was a prospective case-control study.
30392210	2	66	theme	case-control	310:321	arg1	study					323:327	a prospective case-control study	296:327	a prospective case-control study	296:327	Methods: This was a prospective case-control study.
30392210	2	66	theme	case-control	310:321	arg1	This					287:290	This	287:290	This	287:290	Methods: This was a prospective case-control study.
30392210	13	67	theme	Bifidobacterium	2633:2647	arg1	×10					2672:2674	Bifidobacterium 19.680 (6.181, 53.944) ×10(-3)	2633:2678	×10	2672:2674	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	3	68	theme	diagnostic	429:438	arg1	criteria					440:447	diagnostic criteria	429:447	diagnostic criteria	429:447	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	3	69	theme	2010	413:416	arg1	edition					418:424	the 2010 edition	409:424	the 2010 edition of diagnostic criteria	409:447	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	8	70	theme	PICRUST	1322:1328	arg1	software					1330:1337	PICRUST software	1322:1337	PICRUST software	1322:1337	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	0	71	with	children	46:53	arg1	disease					85:91	nonalcoholic fatty liver disease	60:91	nonalcoholic fatty liver disease	60:91	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	14	72	theme	function	3021:3028	arg1	genes					3030:3034	the function genes	3017:3034	the function genes of K01470, K01961 and K07258	3017:3063	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	6	73	theme	body	802:805	arg1	BMI					819:821	BMI	819:821	BMI	819:821	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	6	73	theme	body	802:805	arg1	index					812:816	The body mass index	798:816	The body mass index (BMI)	798:822	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	7	74	theme	microflora	1136:1145	arg1	composition					1093:1103	composition	1093:1103	composition	1093:1103	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	7	74	theme	microflora	1136:1145	arg1	richness					1113:1120	the richness	1109:1120	the richness	1109:1120	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	7	75	from	richness	1113:1120	arg1	groups					1158:1163	the two groups	1150:1163	the two groups	1150:1163	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	13	76	theme	Bifidobacterium	2468:2482	arg1	lower					2522:2526	lower	2522:2526	lower	2522:2526	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	76	theme	Bifidobacterium	2468:2482	arg1	proportion					2438:2447	the proportion	2434:2447	the proportion of Bacteroides and Bifidobacterium in the NAFLD group	2434:2501	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	1	77	theme	fatty	202:206	arg1	NAFLD					223:227	NAFLD	223:227	NAFLD	223:227	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	77	theme	fatty	202:206	arg1	disease					214:220	non-alcoholic fatty liver disease	188:220	non-alcoholic fatty liver disease (NAFLD)	188:228	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	3	78	theme	Affiliated	499:508	arg1	Hospitals					510:518	the Second and First Affiliated Hospitals	478:518	the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University	478:558	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	16	79	theme	differential	3461:3472	arg1	expressions					3479:3489	differential gene expressions	3461:3489	differential gene expressions	3461:3489	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	1	80	theme	microflora	160:169	arg1	role					238:241	the role	234:241	the role of which in pathogenesis of NAFLD	234:275	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	80	theme	microflora	160:169	arg1	composition					121:131	composition	121:131	composition	121:131	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	80	theme	microflora	160:169	arg1	richness					137:144	richness	137:144	richness	137:144	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	14	81	theme	synthesis	3146:3154	arg1	pathways					3090:3097	the pathways	3086:3097	the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism	3086:3203	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	3	82	theme	Chinese	532:538	arg1	Medicine					540:547	Zhejiang Chinese Medicine University	523:558	Zhejiang Chinese Medicine University	523:558	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	5	83	theme	mean	769:772	arg1	age					774:776	the mean age	765:776	the mean age of (9.0±1.2) years	765:795	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	14	84	theme	metabolic	2974:2982	arg1	pathways					2984:2991	26 differential metabolic pathways	2958:2991	26 differential metabolic pathways	2958:2991	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	13	85	theme	genus	2427:2431	arg1	level					2418:2422	the level	2414:2422	the level of genus	2414:2431	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	14	86	theme	fatty	3135:3139	arg1	synthesis					3146:3154	fatty acid synthesis	3135:3154	fatty acid synthesis	3135:3154	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	9	87	theme	flora	1355:1359	arg1	characteristics					1361:1375	The intestinal flora characteristics	1340:1375	The intestinal flora characteristics between the two groups	1340:1398	The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test.
30392210	3	88	dep	Medicine	540:547	arg1	University					549:558	University	549:558	University	549:558	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	2	89	theme	prospective	298:308	arg1	Methods					278:284	Methods	278:284	Methods: This was a prospective case-control study.	278:328	Methods: This was a prospective case-control study.
30392210	2	89	theme	prospective	298:308	arg1	study					323:327	a prospective case-control study	296:327	a prospective case-control study	296:327	Methods: This was a prospective case-control study.
30392210	2	89	theme	prospective	298:308	arg1	This					287:290	This	287:290	This	287:290	Methods: This was a prospective case-control study.
30392210	1	90	theme	liver	208:212	arg1	NAFLD					223:227	NAFLD	223:227	NAFLD	223:227	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	90	theme	liver	208:212	arg1	disease					214:220	non-alcoholic fatty liver disease	188:220	non-alcoholic fatty liver disease (NAFLD)	188:228	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	11	91	theme	diversity	1790:1798	arg1	index					1800:1804	diversity index	1790:1804	diversity index	1790:1804	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	10	92	theme	waist	1489:1493	arg1	circumference					1495:1507	waist circumference	1489:1507	waist circumference	1489:1507	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	5	93	theme	years	791:795	arg1	age					774:776	the mean age	765:776	the mean age of (9.0±1.2) years	765:795	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	13	94	theme	54.721	2684:2689	arg1	×10					2566:2568	11.430, 151.621) ×10(-3)	2549:2572	×10	2566:2568	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	94	theme	54.721	2684:2689	arg1	×10					2709:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10	2529:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3)	2529:2715	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	16	95	theme	metabolic	3434:3442	arg1	pathways					3444:3451	lipid metabolic pathways	3428:3451	lipid metabolic pathways	3428:3451	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	10	96	theme	waist	1642:1646	arg1	88.6±6.6					1663:1670	88.6±6.6	1663:1670	88.6±6.6	1663:1670	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	96	theme	waist	1642:1646	arg1	circumference					1648:1660	waist circumference	1642:1660	waist circumference (88.6±6.6)	1642:1671	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	14	97	theme	proline	3115:3121	arg1	metabolism					3123:3132	arginine and proline metabolism	3102:3132	metabolism	3123:3132	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	11	98	theme	microflora	1820:1829	arg1	index					1800:1804	diversity index	1790:1804	diversity index	1790:1804	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	98	theme	microflora	1820:1829	arg1	abundance					1776:1784	abundance	1776:1784	abundance	1776:1784	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	5	99	theme	of	695:696	arg1	years					709:713	the mean age of (11.0±1.0) years	682:713	the mean age of (11.0±1.0) years; 10 males and 12 females in the control group	682:759	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	12	100	theme	Z=-2.729	2390:2397	arg1	0.000					2334:2338	Thermus 0.033 (0.000, 0.226) ×10(-3)	2319:2354	0.000	2334:2338	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	1	101	theme	non-alcoholic	188:200	arg1	NAFLD					223:227	NAFLD	223:227	NAFLD	223:227	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	101	theme	non-alcoholic	188:200	arg1	disease					214:220	non-alcoholic fatty liver disease	188:220	non-alcoholic fatty liver disease (NAFLD)	188:228	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	14	102	theme	arginine	3102:3109	arg1	metabolism					3123:3132	arginine and proline metabolism	3102:3132	metabolism	3123:3132	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	6	103	theme	fasting	871:877	arg1	glucose					885:891	the fasting blood glucose	867:891	the fasting blood glucose	867:891	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	12	104	theme	Thermus	2319:2325	arg1	0.000					2334:2338	Thermus 0.033 (0.000, 0.226) ×10(-3)	2319:2354	0.000	2334:2338	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	16	105	theme	flora	3360:3364	arg1	disturbances					3366:3377	intestinal flora disturbances	3349:3377	intestinal flora disturbances	3349:3377	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	12	106	dep	Actinobacteri	2216:2228	arg1	P=0.008					2310:2316	P=0.008	2310:2316	P=0.008	2310:2316	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	106	dep	Actinobacteri	2216:2228	arg1	0.000					2367:2371	0.000 (0.000, 0.031) ×10(-3)	2360:2387	0.000	2367:2371	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	106	dep	Actinobacteri	2216:2228	arg1	P=0.006					2400:2406	P=0.006	2400:2406	P=0.006	2400:2406	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	106	dep	Actinobacteri	2216:2228	arg1	-3					2295:2296	-3	2295:2296	-3	2295:2296	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	106	dep	Actinobacteri	2216:2228	arg1	-3					2258:2259	-3	2258:2259	-3	2258:2259	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	106	dep	Actinobacteri	2216:2228	arg1	0.000					2334:2338	Thermus 0.033 (0.000, 0.226) ×10(-3)	2319:2354	0.000	2334:2338	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	106	dep	Actinobacteri	2216:2228	arg1	×10					2291:2293	×10	2291:2293	×10	2291:2293	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	5	107	from	males	719:723	arg1	group					755:759	the control group	743:759	the control group	743:759	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	13	108	theme	78.757	2541:2546	arg1	P=0.014					2728:2734	P=0.014	2728:2734	P=0.014	2728:2734	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	108	theme	78.757	2541:2546	arg1	-3					2713:2714	-3	2713:2714	-3	2713:2714	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	108	theme	78.757	2541:2546	arg1	Z=-2.771					2614:2621	Z=-2.771	2614:2621	Z=-2.771	2614:2621	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	108	theme	78.757	2541:2546	arg1	Z=-2.458					2718:2725	Z=-2.458	2718:2725	Z=-2.458	2718:2725	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	108	theme	78.757	2541:2546	arg1	P=0.006					2624:2630	P=0.006	2624:2630	P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3)	2624:2678	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	108	theme	78.757	2541:2546	arg1	×10					2605:2607	356.821 (161.049, 403.037) ×10(-3)	2578:2611	×10	2605:2607	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	108	theme	78.757	2541:2546	arg1	×10					2566:2568	11.430, 151.621) ×10(-3)	2549:2572	×10	2566:2568	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	108	theme	78.757	2541:2546	arg1	×10					2709:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10	2529:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3)	2529:2715	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	P=0.014					2728:2734	P=0.014	2728:2734	P=0.014	2728:2734	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	-3					2713:2714	-3	2713:2714	-3	2713:2714	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	Z=-2.771					2614:2621	Z=-2.771	2614:2621	Z=-2.771	2614:2621	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	Z=-2.458					2718:2725	Z=-2.458	2718:2725	Z=-2.458	2718:2725	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	P=0.006					2624:2630	P=0.006	2624:2630	P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3)	2624:2678	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	×10					2605:2607	356.821 (161.049, 403.037) ×10(-3)	2578:2611	×10	2605:2607	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	×10					2566:2568	11.430, 151.621) ×10(-3)	2549:2572	×10	2566:2568	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	109	dep	lower	2522:2526	arg1	×10					2709:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10	2529:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3)	2529:2715	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	0	110	from	changes	10:16	arg1	children					46:53	children	46:53	children with nonalcoholic fatty liver disease	46:91	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	13	111	from	Bifidobacterium	2468:2482	arg1	group					2497:2501	the NAFLD group	2487:2501	the NAFLD group	2487:2501	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	9	112	theme	Mann-Whitney	1429:1440	arg1	test					1444:1447	Mann-Whitney U test	1429:1447	Mann-Whitney U test	1429:1447	The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test.
30392210	1	113	dep	composition	121:131	arg1	the					117:119	the	117:119	the	117:119	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	16	114	theme	gene	3474:3477	arg1	expressions					3479:3489	differential gene expressions	3461:3489	differential gene expressions	3461:3489	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	5	115	theme	mean	686:689	arg1	years					709:713	the mean age of (11.0±1.0) years	682:713	the mean age of (11.0±1.0) years; 10 males and 12 females in the control group	682:759	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	1	116	from	richness	137:144	arg1	children					174:181	children	174:181	children with non-alcoholic fatty liver disease (NAFLD)	174:228	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	116	from	richness	137:144	arg1	pathogenesis					255:266	pathogenesis	255:266	pathogenesis of NAFLD	255:275	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	7	117	theme	throughput	1198:1207	arg1	sequencing					1209:1218	16S rDNA high throughput sequencing	1184:1218	16S rDNA high throughput sequencing technology	1184:1229	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	13	118	from	group	2776:2780	arg1	higher					2800:2805	higher	2800:2805	higher	2800:2805	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	118	from	group	2776:2780	arg1	proportion					2742:2751	the proportion	2738:2751	the proportion of Prevotella in NAFLD group	2738:2780	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	7	119	theme	magnetic	1065:1072	arg1	beads					1074:1078	magnetic beads	1065:1078	magnetic beads methods	1065:1086	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	1	120	from	composition	121:131	arg1	children					174:181	children	174:181	children with non-alcoholic fatty liver disease (NAFLD)	174:228	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	120	from	composition	121:131	arg1	pathogenesis					255:266	pathogenesis	255:266	pathogenesis of NAFLD	255:275	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	9	121	theme	Willcoxon	1453:1461	arg1	test					1465:1468	Willcoxon W test	1453:1468	Willcoxon W test	1453:1468	The intestinal flora characteristics between the two groups were compared with t test or Mann-Whitney U test and Willcoxon W test.
30392210	7	122	theme	rDNA	1188:1191	arg1	sequencing					1209:1218	16S rDNA high throughput sequencing	1184:1218	16S rDNA high throughput sequencing technology	1184:1229	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	16	123	theme	NAFLD	3329:3333	arg1	children					3335:3342	NAFLD children	3329:3342	NAFLD children	3329:3342	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	12	124	theme	Actinomycetes	2135:2147	arg1	lower					2153:2157	lower	2153:2157	lower	2153:2157	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	12	124	theme	Actinomycetes	2135:2147	arg1	proportion					2121:2130	the proportion	2117:2130	the proportion of Actinomycetes	2117:2147	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	8	125	theme	differential	1239:1250	arg1	expression					1257:1266	differential gene expression	1239:1266	differential gene expression	1239:1266	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	16	126	theme	NAFLD	3528:3532	arg1	pathogenesis					3512:3523	the pathogenesis	3508:3523	the pathogenesis of NAFLD	3508:3532	Conclusion: NAFLD children have intestinal flora disturbances in both diversity and abundance, which may alter lipid metabolic pathways through differential gene expressions, contributing to the pathogenesis of NAFLD.
30392210	0	127	theme	intestinal	21:30	arg1	microflora					32:41	intestinal microflora	21:41	intestinal microflora	21:41	[Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease].
30392210	13	128	from	proportion	2742:2751	arg1	group					2776:2780	NAFLD group	2770:2780	NAFLD group	2770:2780	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	129	from	Bacteroides	2452:2462	arg1	group					2497:2501	the NAFLD group	2487:2501	the NAFLD group	2487:2501	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	10	130	theme	NAFLD	1541:1545	arg1	group					1547:1551	NAFLD group	1541:1551	NAFLD group	1541:1551	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	11	131	dep	0.70	1956:1959	arg1	0.89					1962:1965	0.89	1962:1965	0.89	1962:1965	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	7	132	dep	composition	1093:1103	arg1	the					1089:1091	the	1089:1091	the	1089:1091	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	8	133	theme	expression	1257:1266	arg1	enrichment					1292:1301	The KO differential gene expression and KEGG signal pathway enrichment	1232:1301	The KO differential gene expression and KEGG signal pathway enrichment	1232:1301	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	11	134	dep	abundance	1776:1784	arg1	The					1772:1774	The	1772:1774	The	1772:1774	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	12	135	theme	0.000	2360:2364	arg1	0.000					2367:2371	0.000 (0.000, 0.031) ×10(-3)	2360:2387	0.000	2367:2371	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	1	136	theme	NAFLD	271:275	arg1	pathogenesis					255:266	pathogenesis	255:266	pathogenesis of NAFLD	255:275	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	12	137	theme	phylum	2109:2114	arg1	level					2100:2104	the level	2096:2104	the level of phylum	2096:2114	At the level of phylum, the proportion of Actinomycetes was lower and the proportion of Thermus was higher in NAFLD group (Actinobacteri 29.807 (14.723, 62.080) ×10(-3) vs. 63.212 (46.133, 172.071) ×10(-3), Z=-2.667, P=0.008; Thermus 0.033 (0.000, 0.226) ×10(-3) vs. 0.000 (0.000, 0.031) ×10(-3), Z=-2.729, P=0.006) .
30392210	6	138	theme	total	894:898	arg1	cholesterol					900:910	total cholesterol	894:910	total cholesterol	894:910	The body mass index (BMI) and waist circumference were recorded, and the fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein were detected.
30392210	13	139	theme	Bacteroides	2529:2539	arg1	P=0.014					2728:2734	P=0.014	2728:2734	P=0.014	2728:2734	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	139	theme	Bacteroides	2529:2539	arg1	-3					2713:2714	-3	2713:2714	-3	2713:2714	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	139	theme	Bacteroides	2529:2539	arg1	Z=-2.771					2614:2621	Z=-2.771	2614:2621	Z=-2.771	2614:2621	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	139	theme	Bacteroides	2529:2539	arg1	Z=-2.458					2718:2725	Z=-2.458	2718:2725	Z=-2.458	2718:2725	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	139	theme	Bacteroides	2529:2539	arg1	P=0.006					2624:2630	P=0.006	2624:2630	P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3)	2624:2678	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	139	theme	Bacteroides	2529:2539	arg1	×10					2605:2607	356.821 (161.049, 403.037) ×10(-3)	2578:2611	×10	2605:2607	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	139	theme	Bacteroides	2529:2539	arg1	×10					2566:2568	11.430, 151.621) ×10(-3)	2549:2572	×10	2566:2568	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	139	theme	Bacteroides	2529:2539	arg1	×10					2709:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10	2529:2711	Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3)	2529:2715	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	8	140	theme	KEGG	1272:1275	arg1	pathway					1284:1290	KEGG signal pathway	1272:1290	KEGG signal pathway	1272:1290	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	5	141	theme	age	691:693	arg1	years					709:713	the mean age of (11.0±1.0) years	682:713	the mean age of (11.0±1.0) years; 10 males and 12 females in the control group	682:759	Among the patients, 10 were males and 9 were females, at the mean age of (11.0±1.0) years; 10 males and 12 females in the control group, at the mean age of (9.0±1.2) years.
30392210	1	142	with	children	174:181	arg1	NAFLD					223:227	NAFLD	223:227	NAFLD	223:227	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	1	142	with	children	174:181	arg1	disease					214:220	non-alcoholic fatty liver disease	188:220	non-alcoholic fatty liver disease (NAFLD)	188:228	Objective: To analyze the composition and richness of intestinal microflora in children with non-alcoholic fatty liver disease (NAFLD) and the role of which in pathogenesis of NAFLD.
30392210	10	143	theme	71.5±6.3	1678:1685	arg1	cm					1688:1689	cm	1688:1689	cm	1688:1689	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	8	144	theme	pathway	1284:1290	arg1	enrichment					1292:1301	The KO differential gene expression and KEGG signal pathway enrichment	1232:1301	The KO differential gene expression and KEGG signal pathway enrichment	1232:1301	The KO differential gene expression and KEGG signal pathway enrichment were analyzed with PICRUST software.
30392210	10	145	theme	control	1571:1577	arg1	group					1579:1583	the control group	1567:1583	the control group	1567:1583	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	13	146	theme	Bacteroides	2452:2462	arg1	lower					2522:2526	lower	2522:2526	lower	2522:2526	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	146	theme	Bacteroides	2452:2462	arg1	proportion					2438:2447	the proportion	2434:2447	the proportion of Bacteroides and Bifidobacterium in the NAFLD group	2434:2501	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	13	147	theme	NAFLD	2491:2495	arg1	group					2497:2501	the NAFLD group	2487:2501	the NAFLD group	2487:2501	At the level of genus, the proportion of Bacteroides and Bifidobacterium in the NAFLD group were significantly lower (Bacteroides 78.757 (11.430, 151.621) ×10(-3) vs. 356.821 (161.049, 403.037) ×10(-3), Z=-2.771, P=0.006; Bifidobacterium 19.680 (6.181, 53.944) ×10(-3) vs. 54.721 (31.911, 146.410) ×10(-3), Z=-2.458, P=0.014); the proportion of Prevotella in NAFLD group was significantly higher (3.089 (0.165, 63.502) ×10(-3) vs. 0.432 (0.029, 2.257) ×10(-3), Z=-2.112, P=0.035).
30392210	3	148	dep	November	335:342	arg1	June					352:355	June	352:355	June	352:355	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	3	148	dep	November	335:342	arg1	to					349:350	to	349:350	to	349:350	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	3	149	theme	criteria	440:447	arg1	edition					418:424	the 2010 edition	409:424	the 2010 edition of diagnostic criteria	409:447	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
30392210	14	150	theme	K07258	3058:3063	arg1	genes					3030:3034	the function genes	3017:3034	the function genes of K01470, K01961 and K07258	3017:3063	Based on the KEGG database, 78 differentially expressed genes and 26 differential metabolic pathways were found, among which the function genes of K01470, K01961 and K07258 were concentrated in the pathways of arginine and proline metabolism, fatty acid synthesis, and polysaccharides biosynthesis and metabolism.
30392210	7	151	theme	intestinal	1125:1134	arg1	microflora					1136:1145	intestinal microflora	1125:1145	intestinal microflora	1125:1145	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	7	152	theme	sequencing	1209:1218	arg1	technology					1220:1229	16S rDNA high throughput sequencing technology	1184:1229	16S rDNA high throughput sequencing technology	1184:1229	Feces were collected and the fecal microorganisms were extracted with magnetic beads methods; the composition and the richness of intestinal microflora in the two groups were detected with 16S rDNA high throughput sequencing technology.
30392210	11	153	dep	index	1870:1874	arg1	0.88					1978:1981	0.88	1978:1981	0.88	1978:1981	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	P=0.015					2001:2007	P=0.015	2001:2007	P=0.015	2001:2007	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	index					1944:1948	index	1944:1948	index	1944:1948	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	index					2014:2018	ACE index 235.76 (205.26, 361.94)	2010:2042	index	2014:2018	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	0.90					1972:1975	0.90	1972:1975	0.90	1972:1975	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	Z=-2.065					1917:1924	Z=-2.065	1917:1924	Z=-2.065	1917:1924	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	326.96					2048:2053	326.96	2048:2053	326.96	2048:2053	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	Z=-2.431					1991:1998	Z=-2.431	1991:1998	Z=-2.431	1991:1998	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	P=0.039					1927:1933	P=0.039	1927:1933	P=0.039	1927:1933	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	Z=-2.092					2073:2080	Z=-2.092	2073:2080	Z=-2.092	2073:2080	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	4.54					1888:1891	4.54	1888:1891	4.54	1888:1891	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	0.70					1956:1959	0.70	1956:1959	0.70	1956:1959	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	11	153	dep	index	1870:1874	arg1	P=0.036					2083:2089	P=0.036	2083:2089	P=0.036	2083:2089	The abundance and diversity index of intestinal microflora were lower in the NAFLD group (Shannon index 3.99 (3.13, 4.54) vs. 4.63 (4.21, 4.81), Z=-2.065, P=0.039; Simpson index 0.85 (0.70, 0.89) vs. 0.90 (0.88, 0.93), Z=-2.431, P=0.015; ACE index 235.76 (205.26, 361.94) vs. 326.96 (275.34, 368.65), Z=-2.092, P=0.036).
30392210	10	154	dep	higher	1531:1536	arg1	BMI					1586:1588	BMI	1586:1588	BMI	1586:1588	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	154	dep	higher	1531:1536	arg1	18.2±1.5					1606:1613	18.2±1.5	1606:1613	18.2±1.5	1606:1613	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	10	154	dep	higher	1531:1536	arg1	25.1±2.7					1591:1598	25.1±2.7	1591:1598	25.1±2.7	1591:1598	Results: The BMI, waist circumference and triglyceride were higher in NAFLD group than those in the control group (BMI (25.1±2.7) vs. (18.2±1.5)kg/m(2), t=9.912, P=0.000; waist circumference (88.6±6.6) vs. (71.5±6.3) cm, t=8.520, P=0.000; triglyceride (0.9±0.4) vs.(0.7±0.3)mmol/L, t=2.060, P=0.046).
30392210	3	155	theme	Second	482:487	arg1	Hospitals					510:518	the Second and First Affiliated Hospitals	478:518	the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University	478:558	From November 2015 to June 2017, 19 children diagnosed with NAFLD according to the 2010 edition of diagnostic criteria were enrolled voluntarily in the Second and First Affiliated Hospitals of Zhejiang Chinese Medicine University.
31628258	0	0	theme	Capillary	75:83	arg1	Electrophoresis					85:99	Capillary Electrophoresis	75:99	Capillary Electrophoresis	75:99	Sample Preparation Scale-Up for Deep N-glycomic Analysis of Human Serum by Capillary Electrophoresis and CE-ESI-MS.
31628258	1	1	theme	concentration	346:358	arg1	requirement					360:370	the higher sample concentration requirement	328:370	the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	328:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	2	2	dep	denaturing	499:508	arg1	temperature					478:488	temperature	478:488	temperature	478:488	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	2	2	dep	denaturing	499:508	arg1	gradient					490:497	gradient	490:497	gradient	490:497	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	3	3	theme	mediated	780:787	arg1	release					789:795	enhanced PNGase F mediated release	762:795	enhanced PNGase F mediated release of the N-linked carbohydrates	762:825	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	1	4	theme	laser	263:267	arg1	detection					299:307	laser induced fluorescence (CE-LIF) detection	263:307	laser induced fluorescence (CE-LIF) detection	263:307	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	3	5	theme	PNGase	771:776	arg1	F					778:778	PNGase F	771:778	enhanced PNGase F mediated release of the N-linked carbohydrates	762:825	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	5	6	theme	deep	1008:1011	arg1	analysis					1020:1027	deep CE-LIF analysis	1008:1027	deep CE-LIF analysis of the human serum N-glycome	1008:1056	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	1	7	theme	induced	269:275	arg1	detection					299:307	laser induced fluorescence (CE-LIF) detection	263:307	laser induced fluorescence (CE-LIF) detection	263:307	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	5	8	dep	Processing	954:963	arg1	enabled					1000:1006	enabled	1000:1006	enabled deep CE-LIF analysis of the human serum N-glycome	1000:1056	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	5	8	dep	Processing	954:963	arg1	provided					1062:1069	provided	1062:1069	provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode	1062:1155	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	5	9	theme	negative	1132:1139	arg1	mode					1152:1155	negative ionization mode	1132:1155	negative ionization mode	1132:1155	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	4	10	theme	liberated	832:840	arg1	oligosaccharides					842:857	The liberated oligosaccharides	828:857	The liberated oligosaccharides	828:857	The liberated oligosaccharides were tagged with aminopyrene-trisulfonate, utilizing a modified evaporative labeling protocol.
31628258	1	11	theme	fluorescence	277:288	arg1	detection					299:307	laser induced fluorescence (CE-LIF) detection	263:307	laser induced fluorescence (CE-LIF) detection	263:307	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	1	12	theme	electrospray	375:386	arg1	spectrometry					404:415	electrospray ionization mass spectrometry	375:415	electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	375:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	2	13	gly	glycoproteins	581:593	arg1	glycoproteins					581:593	glycoproteins	581:593	glycoproteins	581:593	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	1	14	theme	ionization	388:397	arg1	spectrometry					404:415	electrospray ionization mass spectrometry	375:415	electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	375:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	2	15	dep	novel	471:475	arg1	denaturing					499:508	denaturing	499:508	denaturing	499:508	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	5	16	theme	appropriate	1075:1085	arg1	material					1097:1104	material	1097:1104	material	1097:1104	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	5	16	theme	appropriate	1075:1085	arg1	amount					1087:1092	the appropriate amount	1071:1092	the appropriate amount of material	1071:1104	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	2	17	theme	magnetic	555:562	arg1	bead					564:567	amine functionalized magnetic bead	534:567	amine functionalized magnetic bead partitioned glycoproteins	534:593	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	1	18	theme	mass	399:402	arg1	spectrometry					404:415	electrospray ionization mass spectrometry	375:415	electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	375:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	4	19	theme	labeling	935:942	arg1	protocol					944:951	a modified evaporative labeling protocol	912:951	a modified evaporative labeling protocol	912:951	The liberated oligosaccharides were tagged with aminopyrene-trisulfonate, utilizing a modified evaporative labeling protocol.
31628258	1	20	dep	introduce	119:127	arg1	workflow					161:168	workflow	161:168	workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	161:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	1	21	theme	deep	184:187	arg1	analysis					201:208	deep N-glycomics analysis	184:208	deep N-glycomics analysis of the human serum	184:227	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	1	22	theme	spectrometry	404:415	arg1	requirement					360:370	the higher sample concentration requirement	328:370	the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	328:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	2	23	theme	functionalized	540:553	arg1	bead					564:567	amine functionalized magnetic bead	534:567	amine functionalized magnetic bead partitioned glycoproteins	534:593	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	5	24	theme	human	1036:1040	arg1	N-glycome					1048:1056	the human serum N-glycome	1032:1056	the human serum N-glycome	1032:1056	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	5	25	with	samples	969:975	arg1	workflow					991:998	this new workflow	982:998	this new workflow	982:998	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	1	26	theme	N-glycomics	189:199	arg1	analysis					201:208	deep N-glycomics analysis	184:208	deep N-glycomics analysis of the human serum	184:227	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	0	27	theme	Sample	0:5	arg1	Preparation					7:17	Sample Preparation	0:17	Sample Preparation	0:17	Sample Preparation Scale-Up for Deep N-glycomic Analysis of Human Serum by Capillary Electrophoresis and CE-ESI-MS.
31628258	1	28	theme	CE-LIF	291:296	arg1	detection					299:307	laser induced fluorescence (CE-LIF) detection	263:307	laser induced fluorescence (CE-LIF) detection	263:307	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	3	29	theme	carbohydrates	813:825	arg1	release					789:795	enhanced PNGase F mediated release	762:795	enhanced PNGase F mediated release of the N-linked carbohydrates	762:825	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	5	30	theme	serum	1042:1046	arg1	N-glycome					1048:1056	the human serum N-glycome	1032:1056	the human serum N-glycome	1032:1056	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	2	31	theme	novel	471:475	arg1	protocol					510:517	A novel, temperature gradient denaturing protocol	469:517	A novel, temperature gradient denaturing protocol	469:517	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	5	32	theme	ionization	1141:1150	arg1	mode					1152:1155	negative ionization mode	1132:1155	negative ionization mode	1132:1155	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	5	33	theme	N-glycome	1048:1056	arg1	analysis					1020:1027	deep CE-LIF analysis	1008:1027	deep CE-LIF analysis of the human serum N-glycome	1008:1056	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	3	34	theme	serum	705:709	arg1	well					742:745	well	742:745	well	742:745	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	3	34	theme	serum	705:709	arg1	content					690:696	the free sugar content	675:696	the free sugar content of the serum	675:709	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	5	35	from	analysis	1120:1127	arg1	mode					1152:1155	negative ionization mode	1132:1155	negative ionization mode	1132:1155	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	5	36	theme	new	987:989	arg1	workflow					991:998	this new workflow	982:998	this new workflow	982:998	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	0	37	theme	N-glycomic	37:46	arg1	Analysis					48:55	Deep N-glycomic Analysis	32:55	Deep N-glycomic Analysis of Human Serum	32:70	Sample Preparation Scale-Up for Deep N-glycomic Analysis of Human Serum by Capillary Electrophoresis and CE-ESI-MS.
31628258	3	38	theme	N-linked	804:811	arg1	carbohydrates					813:825	the N-linked carbohydrates	800:825	the N-linked carbohydrates	800:825	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	5	39	theme	CE-ESI-MS	1110:1118	arg1	analysis					1120:1127	CE-ESI-MS analysis	1110:1127	CE-ESI-MS analysis in negative ionization mode	1110:1155	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	1	40	theme	human	217:221	arg1	serum					223:227	the human serum	213:227	the human serum	213:227	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	0	41	theme	Deep	32:35	arg1	Analysis					48:55	Deep N-glycomic Analysis	32:55	Deep N-glycomic Analysis of Human Serum	32:70	Sample Preparation Scale-Up for Deep N-glycomic Analysis of Human Serum by Capillary Electrophoresis and CE-ESI-MS.
31628258	1	42	theme	capillary	430:438	arg1	CE-ESI-MS					457:465	CE-ESI-MS	457:465	CE-ESI-MS	457:465	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	1	42	theme	capillary	430:438	arg1	electrophoresis					440:454	capillary electrophoresis	430:454	capillary electrophoresis (CE-ESI-MS)	430:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	1	43	theme	serum	223:227	arg1	analysis					201:208	deep N-glycomics analysis	184:208	deep N-glycomics analysis of the human serum	184:227	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	2	44	theme	amine	534:538	arg1	bead					564:567	amine functionalized magnetic bead	534:567	amine functionalized magnetic bead partitioned glycoproteins	534:593	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	4	45	theme	evaporative	923:933	arg1	protocol					944:951	a modified evaporative labeling protocol	912:951	a modified evaporative labeling protocol	912:951	The liberated oligosaccharides were tagged with aminopyrene-trisulfonate, utilizing a modified evaporative labeling protocol.
31628258	3	46	theme	F	778:778	arg1	release					789:795	enhanced PNGase F mediated release	762:795	enhanced PNGase F mediated release of the N-linked carbohydrates	762:825	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	5	47	theme	CE-LIF	1013:1018	arg1	analysis					1020:1027	deep CE-LIF analysis	1008:1027	deep CE-LIF analysis of the human serum N-glycome	1008:1056	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	3	48	theme	enhanced	762:769	arg1	release					789:795	enhanced PNGase F mediated release	762:795	enhanced PNGase F mediated release of the N-linked carbohydrates	762:825	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	4	49	theme	modified	914:921	arg1	protocol					944:951	a modified evaporative labeling protocol	912:951	a modified evaporative labeling protocol	912:951	The liberated oligosaccharides were tagged with aminopyrene-trisulfonate, utilizing a modified evaporative labeling protocol.
31628258	1	50	theme	higher	332:337	arg1	requirement					360:370	the higher sample concentration requirement	328:370	the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	328:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	2	51	theme	precipitation	633:645	arg1	issue					647:651	the otherwise prevalent precipitation issue	609:651	the otherwise prevalent precipitation issue	609:651	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	3	52	theme	sugar	684:688	arg1	well					742:745	well	742:745	well	742:745	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	3	52	theme	sugar	684:688	arg1	content					690:696	the free sugar content	675:696	the free sugar content of the serum	675:709	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	2	53	theme	prevalent	623:631	arg1	precipitation					633:645	the otherwise prevalent precipitation	609:645	the otherwise prevalent precipitation issue	609:651	A novel, temperature gradient denaturing protocol was applied on amine functionalized magnetic bead partitioned glycoproteins to circumvent the otherwise prevalent precipitation issue.
31628258	5	54	theme	material	1097:1104	arg1	material					1097:1104	material	1097:1104	material	1097:1104	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	5	54	theme	material	1097:1104	arg1	amount					1087:1092	the appropriate amount	1071:1092	the appropriate amount of material	1071:1104	Processing the samples with this new workflow enabled deep CE-LIF analysis of the human serum N-glycome and provided the appropriate amount of material for CE-ESI-MS analysis in negative ionization mode.
31628258	1	55	with	electrophoresis	242:256	arg1	detection					299:307	laser induced fluorescence (CE-LIF) detection	263:307	laser induced fluorescence (CE-LIF) detection	263:307	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	1	56	theme	efficient	132:140	arg1	preparation					149:159	an efficient sample preparation	129:159	an efficient sample preparation	129:159	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	1	57	theme	capillary	232:240	arg1	electrophoresis					242:256	capillary electrophoresis	232:256	capillary electrophoresis with laser induced fluorescence (CE-LIF) detection	232:307	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	0	58	theme	Serum	66:70	arg1	Analysis					48:55	Deep N-glycomic Analysis	32:55	Deep N-glycomic Analysis of Human Serum	32:70	Sample Preparation Scale-Up for Deep N-glycomic Analysis of Human Serum by Capillary Electrophoresis and CE-ESI-MS.
31628258	3	59	link	N-linked	804:811	arg1	carbohydrates					813:825	the N-linked carbohydrates	800:825	the N-linked carbohydrates	800:825	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	1	60	theme	sample	142:147	arg1	preparation					149:159	an efficient sample preparation	129:159	an efficient sample preparation	129:159	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	0	61	theme	Human	60:64	arg1	Serum					66:70	Human Serum	60:70	Human Serum	60:70	Sample Preparation Scale-Up for Deep N-glycomic Analysis of Human Serum by Capillary Electrophoresis and CE-ESI-MS.
31628258	1	62	theme	sample	339:344	arg1	requirement					360:370	the higher sample concentration requirement	328:370	the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS)	328:466	We introduce an efficient sample preparation workflow to facilitate deep N-glycomics analysis of the human serum by capillary electrophoresis with laser induced fluorescence (CE-LIF) detection and to accommodate the higher sample concentration requirement of electrospray ionization mass spectrometry connected to capillary electrophoresis (CE-ESI-MS).
31628258	3	63	theme	free	679:682	arg1	well					742:745	well	742:745	well	742:745	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31628258	3	63	theme	free	679:682	arg1	content					690:696	the free sugar content	675:696	the free sugar content of the serum	675:709	During this process, the free sugar content of the serum was significantly decreased as well, accommodating enhanced PNGase F mediated release of the N-linked carbohydrates.
31357165	4	0	theme	lower	547:551	arg1	length					556:561	lower V2 length	547:561	lower V2 length	547:561	At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs.
31357165	0	1	theme	Clinical	57:64	arg1	correlates					66:75	Clinical correlates	57:75	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.	0:76	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
31357165	2	2	theme	viro-immunological	309:326	arg1	features					328:335	clinical and viro-immunological features	296:335	clinical and viro-immunological features	296:335	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	2	3	from	association	279:289	arg1	patients					262:269	naive HIV-1 infected patients	241:269	naive HIV-1 infected patients	241:269	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	2	4	theme	HIV-1	247:251	arg1	patients					262:269	naive HIV-1 infected patients	241:269	naive HIV-1 infected patients	241:269	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	2	5	theme	infected	253:260	arg1	patients					262:269	naive HIV-1 infected patients	241:269	naive HIV-1 infected patients	241:269	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	3	6	theme	Gp120	338:342	arg1	sequences					344:352	Gp120 sequences	338:352	Gp120 sequences	338:352	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	2	7	theme	naive	241:245	arg1	patients					262:269	naive HIV-1 infected patients	241:269	naive HIV-1 infected patients	241:269	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	4	8	theme	V2	553:554	arg1	length					556:561	lower V2 length	547:561	lower V2 length	547:561	At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs.
31357165	8	9	theme	clinical	1038:1045	arg1	significance					1047:1058	the clinical significance	1034:1058	the clinical significance of these associations	1034:1080	Further studies to deeply explore the clinical significance of these associations are warranted.
31357165	1	10	theme	α4β7	144:147	arg1	integrin					149:156	α4β7 integrin	144:156	α4β7 integrin	144:156	The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing.
31357165	7	11	theme	recent	970:975	arg1	infections					977:986	recent infections	970:986	recent infections	970:986	Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM.
31357165	3	12	theme	V2	502:503	arg1	α4β7-binding-motif					480:497	179-181tripeptide α4β7-binding-motif	462:497	179-181tripeptide α4β7-binding-motif of V2	462:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	12	theme	V2	502:503	arg1	net-charge					442:451	net-charge	442:451	net-charge (NC)	442:456	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	12	theme	V2	502:503	arg1	NC					454:455	NC	454:455	NC	454:455	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	12	theme	V2	502:503	arg1	V2					502:503	V2	502:503	V2	502:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	12	theme	V2	502:503	arg1	sites					428:432	potential N-linked glycosylation sites	395:432	potential N-linked glycosylation sites (PNGs)	395:439	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	12	theme	V2	502:503	arg1	length					387:392	length	387:392	length	387:392	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	12	theme	V2	502:503	arg1	PNGs					435:438	PNGs	435:438	PNGs	435:438	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	13	theme	glycosylation	414:426	arg1	PNGs					435:438	PNGs	435:438	PNGs	435:438	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	13	theme	glycosylation	414:426	arg1	V2					502:503	V2	502:503	V2	502:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	13	theme	glycosylation	414:426	arg1	sites					428:432	potential N-linked glycosylation sites	395:432	potential N-linked glycosylation sites (PNGs)	395:439	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	4	14	theme	multivariate	524:535	arg1	analysis					537:544	multivariate analysis	524:544	multivariate analysis	524:544	At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs.
31357165	3	15	link	N-linked	405:412	arg1	PNGs					435:438	PNGs	435:438	PNGs	435:438	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	15	link	N-linked	405:412	arg1	V2					502:503	V2	502:503	V2	502:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	15	link	N-linked	405:412	arg1	sites					428:432	potential N-linked glycosylation sites	395:432	potential N-linked glycosylation sites (PNGs)	395:439	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	8	16	theme	Further	1000:1006	arg1	studies					1008:1014	Further studies	1000:1014	Further studies to deeply explore the clinical significance of these associations	1000:1080	Further studies to deeply explore the clinical significance of these associations are warranted.
31357165	3	17	theme	potential	395:403	arg1	PNGs					435:438	PNGs	435:438	PNGs	435:438	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	17	theme	potential	395:403	arg1	V2					502:503	V2	502:503	V2	502:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	17	theme	potential	395:403	arg1	sites					428:432	potential N-linked glycosylation sites	395:432	potential N-linked glycosylation sites (PNGs)	395:439	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	0	18	theme	V2	21:22	arg1	domain					28:33	HIV-1 V2 env domain	15:33	HIV-1 V2 env domain	15:33	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
31357165	1	19	theme	HIV	82:84	arg1	tripeptide					113:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing.
31357165	4	20	theme	low	593:595	arg1	cells					601:605	low CD4 cells	593:605	low CD4 cells	593:605	At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs.
31357165	0	21	theme	HIV-1	15:19	arg1	domain					28:33	HIV-1 V2 env domain	15:33	HIV-1 V2 env domain	15:33	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
31357165	5	22	theme	greater	646:652	arg1	variability					654:664	A greater variability	644:664	A greater variability	644:664	A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses.
31357165	1	23	theme	V2179-181	86:94	arg1	tripeptide					113:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing.
31357165	5	24	theme	tropic	773:778	arg1	viruses					780:786	X4 tropic viruses	770:786	X4 tropic viruses	770:786	A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses.
31357165	0	25	theme	domain	28:33	arg1	Variability					0:10	Variability	0:10	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.	0:76	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
31357165	2	26	theme	clinical	296:303	arg1	features					328:335	clinical and viro-immunological features	296:335	clinical and viro-immunological features	296:335	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	2	27	with	association	279:289	arg1	features					328:335	clinical and viro-immunological features	296:335	clinical and viro-immunological features	296:335	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	5	28	theme	X4	770:771	arg1	viruses					780:786	X4 tropic viruses	770:786	X4 tropic viruses	770:786	A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses.
31357165	0	29	theme	env	24:26	arg1	domain					28:33	HIV-1 V2 env domain	15:33	HIV-1 V2 env domain	15:33	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
31357165	5	30	from	positions	676:684	arg1	sequences					740:748	B sequences	738:748	B sequences	738:748	A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses.
31357165	8	31	theme	associations	1069:1080	arg1	significance					1047:1058	the clinical significance	1034:1058	the clinical significance of these associations	1034:1080	Further studies to deeply explore the clinical significance of these associations are warranted.
31357165	1	32	theme	GALT	184:187	arg1	homing					189:194	GALT homing	184:194	GALT homing	184:194	The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing.
31357165	0	33	theme	integrin	39:46	arg1	binding					48:54	integrin binding	39:54	integrin binding	39:54	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
31357165	3	34	theme	N-linked	405:412	arg1	PNGs					435:438	PNGs	435:438	PNGs	435:438	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	34	theme	N-linked	405:412	arg1	V2					502:503	V2	502:503	V2	502:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	34	theme	N-linked	405:412	arg1	sites					428:432	potential N-linked glycosylation sites	395:432	potential N-linked glycosylation sites (PNGs)	395:439	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	5	35	from	163	755:757	arg1	viruses					780:786	X4 tropic viruses	770:786	X4 tropic viruses	770:786	A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses.
31357165	8	36	dep	studies	1008:1014	arg1	explore					1026:1032	explore	1026:1032	to deeply explore the clinical significance of these associations	1016:1080	Further studies to deeply explore the clinical significance of these associations are warranted.
31357165	1	37	theme	HXB2	97:100	arg1	tripeptide					113:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing.
31357165	7	38	theme	recent	906:911	arg1	infections					913:922	recent infections	906:922	recent infections	906:922	Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM.
31357165	3	39	gly	glycosylation	414:426	arg2	PNGs					435:438	PNGs	435:438	PNGs	435:438	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	39	gly	glycosylation	414:426	arg2	sites					428:432	potential N-linked glycosylation sites	395:432	potential N-linked glycosylation sites (PNGs)	395:439	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	39	gly	glycosylation	414:426	arg2	V2					502:503	V2	502:503	V2	502:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	3	39	gly	glycosylation	414:426	arg1	V2					502:503	V2	502:503	V2	502:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	2	40	theme	V2	223:224	arg1	variability					226:236	V2 variability	223:236	V2 variability in naive HIV-1 infected patients	223:269	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	1	41	theme	numbering	102:110	arg1	tripeptide					113:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide	78:122	The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing.
31357165	2	42	from	variability	226:236	arg1	patients					262:269	naive HIV-1 infected patients	241:269	naive HIV-1 infected patients	241:269	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	4	43	theme	higher	567:572	arg1	NC					574:575	higher NC	567:575	higher NC	567:575	At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs.
31357165	5	44	theme	B	738:738	arg1	sequences					740:748	B sequences	738:748	B sequences	738:748	A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses.
31357165	7	45	located	found	961:965	arg2	Val181					950:955	Val181	950:955	Val181	950:955	Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM.
31357165	7	45	located	found	961:965	arg1	infections					977:986	recent infections	970:986	recent infections	970:986	Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM.
31357165	2	46	with	variability	226:236	arg1	features					328:335	clinical and viro-immunological features	296:335	clinical and viro-immunological features	296:335	Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features.
31357165	7	47	located	observed	881:888	arg2	Leu179					854:859	Leu179	854:859	Leu179	854:859	Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM.
31357165	7	47	located	observed	881:888	arg1	non-B					893:897	non-B	893:897	non-B	893:897	Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM.
31357165	4	48	theme	CD4	597:599	arg1	cells					601:605	low CD4 cells	593:605	low CD4 cells	593:605	At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs.
31357165	3	49	theme	179-181tripeptide	462:478	arg1	α4β7-binding-motif					480:497	179-181tripeptide α4β7-binding-motif	462:497	179-181tripeptide α4β7-binding-motif of V2	462:503	Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated.
31357165	6	50	theme	common	806:811	arg1	tripeptide					813:822	the most common tripeptide	797:822	the most common tripeptide	797:822	LDV was the most common tripeptide.
31357165	6	50	theme	common	806:811	arg1	LDV					789:791	LDV	789:791	LDV	789:791	LDV was the most common tripeptide.
31357165	0	51	dep	Variability	0:10	arg1	correlates					66:75	Clinical correlates	57:75	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.	0:76	Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates.
31022851	6	0	theme	laccases	1024:1031	arg1	properties					1010:1019	enzymatic properties	1000:1019	enzymatic properties of laccases	1000:1031	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	1	1	theme	extensive	159:167	arg1	number					169:174	an extensive number	156:174	an extensive number of actual and potential industrial applications	156:222	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	6	2	theme	properties	1010:1019	arg1	moderation					986:995	moderation	986:995	moderation of enzymatic properties of laccases	986:1031	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	6	3	gly	deglycosylation	802:816	arg1	laccases					835:842	four selected laccases	821:842	four selected laccases	821:842	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	6	4	theme	enzymatic	1000:1008	arg1	properties					1010:1019	enzymatic properties	1000:1019	enzymatic properties of laccases	1000:1031	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	6	5	theme	laccases	835:842	arg1	deglycosylation					802:816	the deglycosylation	798:816	the deglycosylation of four selected laccases by Endo H and PNGase F	798:865	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	4	6	contain	had	539:541	arg2	sequences					560:568	the same primary sequences	543:568	the same primary sequences	543:568	Although all seven laccases had the same primary sequences, there was a little variation in their molecular weights and thermostabilities.
31022851	4	6	contain	had	539:541	arg1	laccases					530:537	all seven laccases	520:537	all seven laccases	520:537	Although all seven laccases had the same primary sequences, there was a little variation in their molecular weights and thermostabilities.
31022851	4	7	theme	little	583:588	arg1	variation					590:598	a little variation	581:598	a little variation	581:598	Although all seven laccases had the same primary sequences, there was a little variation in their molecular weights and thermostabilities.
31022851	0	8	theme	Glycosylation	89:101	arg1	Matter					103:108	Glycosylation Matter	89:108	Glycosylation Matter	89:108	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	5	9	theme	significant	674:684	arg1	differences					686:696	statistically significant differences	660:696	statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS	660:775	Moreover, statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS were observed.
31022851	6	10	theme	selected	826:833	arg1	laccases					835:842	four selected laccases	821:842	four selected laccases	821:842	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	3	11	theme	Russia	503:508	arg1	regions					484:490	regions	484:490	regions of central Russia	484:508	In the current study we have isolated and characterized seven laccases from different strains of Steccherinum ochraceum obtained from regions of central Russia.
31022851	5	12	theme	substrates	757:766	arg1	oxidation					735:743	oxidation	735:743	oxidation of phenolic substrates and ABTS	735:775	Moreover, statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS were observed.
31022851	0	13	from	Strains	49:55	arg1	Properties					23:32	Variable Properties	14:32	Variable Properties from Different Strains of Steccherinum ochraceum	14:81	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	3	14	theme	different	426:434	arg1	strains					436:442	different strains	426:442	different strains of Steccherinum ochraceum obtained from regions of central Russia	426:508	In the current study we have isolated and characterized seven laccases from different strains of Steccherinum ochraceum obtained from regions of central Russia.
31022851	1	15	with	oxidases	142:149	arg1	number					169:174	an extensive number	156:174	an extensive number of actual and potential industrial applications	156:222	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	6	16	gly	glycosylation	969:981	arg1	properties					1010:1019	enzymatic properties	1000:1019	enzymatic properties of laccases	1000:1031	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	1	17	theme	actual	179:184	arg1	number					169:174	an extensive number	156:174	an extensive number of actual and potential industrial applications	156:222	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	5	18	theme	ABTS	772:775	arg1	oxidation					735:743	oxidation	735:743	oxidation of phenolic substrates and ABTS	735:775	Moreover, statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS were observed.
31022851	4	19	theme	primary	552:558	arg1	sequences					560:568	the same primary sequences	543:568	the same primary sequences	543:568	Although all seven laccases had the same primary sequences, there was a little variation in their molecular weights and thermostabilities.
31022851	1	20	theme	potential	190:198	arg1	applications					211:222	potential industrial applications	190:222	potential industrial applications	190:222	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	3	21	theme	current	357:363	arg1	study					365:369	the current study	353:369	the current study	353:369	In the current study we have isolated and characterized seven laccases from different strains of Steccherinum ochraceum obtained from regions of central Russia.
31022851	4	22	theme	same	547:550	arg1	sequences					560:568	the same primary sequences	543:568	the same primary sequences	543:568	Although all seven laccases had the same primary sequences, there was a little variation in their molecular weights and thermostabilities.
31022851	5	23	theme	catalytic	711:719	arg1	parameters					721:730	laccases' catalytic parameters	701:730	laccases' catalytic parameters of oxidation of phenolic substrates and ABTS	701:775	Moreover, statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS were observed.
31022851	3	24	theme	ochraceum	460:468	arg1	strains					436:442	different strains	426:442	different strains of Steccherinum ochraceum obtained from regions of central Russia	426:508	In the current study we have isolated and characterized seven laccases from different strains of Steccherinum ochraceum obtained from regions of central Russia.
31022851	0	25	theme	Variable	14:21	arg1	Properties					23:32	Variable Properties	14:32	Variable Properties from Different Strains of Steccherinum ochraceum	14:81	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	6	26	theme	N-linked	960:967	arg1	glycosylation					969:981	N-linked glycosylation	960:981	N-linked glycosylation	960:981	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	3	27	theme	central	495:501	arg1	Russia					503:508	central Russia	495:508	central Russia	495:508	In the current study we have isolated and characterized seven laccases from different strains of Steccherinum ochraceum obtained from regions of central Russia.
31022851	2	28	from	strains	273:279	arg1	laccases					242:249	laccases	242:249	laccases from different fungal strains	242:279	It is known that laccases from different fungal strains may vary in properties; however, the reason of this remains unclear.
31022851	1	29	theme	applications	211:222	arg1	number					169:174	an extensive number	156:174	an extensive number of actual and potential industrial applications	156:222	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	0	30	theme	Different	39:47	arg1	Strains					49:55	Different Strains	39:55	Different Strains of Steccherinum ochraceum	39:81	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	2	31	theme	this	328:331	arg1	reason					318:323	the reason	314:323	the reason of this	314:331	It is known that laccases from different fungal strains may vary in properties; however, the reason of this remains unclear.
31022851	6	32	link	N-linked	960:967	arg1	glycosylation					969:981	N-linked glycosylation	960:981	N-linked glycosylation	960:981	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	5	33	theme	oxidation	735:743	arg1	parameters					721:730	laccases' catalytic parameters	701:730	laccases' catalytic parameters of oxidation of phenolic substrates and ABTS	701:775	Moreover, statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS were observed.
31022851	5	34	from	differences	686:696	arg1	parameters					721:730	laccases' catalytic parameters	701:730	laccases' catalytic parameters of oxidation of phenolic substrates and ABTS	701:775	Moreover, statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS were observed.
31022851	6	35	theme	substantial	940:950	arg1	role					952:955	a substantial role	938:955	a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases	938:1031	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	6	36	theme	glycosylation	969:981	arg1	role					952:955	a substantial role	938:955	a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases	938:1031	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	6	37	theme	PNGase	858:863	arg1	F					865:865	PNGase F	858:865	PNGase F	858:865	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	1	38	theme	blue	124:127	arg1	oxidases					142:149	blue multi-copper oxidases	124:149	blue multi-copper oxidases	124:149	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	1	38	theme	blue	124:127	arg1	Laccases					111:118	Laccases	111:118	Laccases	111:118	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	6	39	from	role	952:955	arg1	moderation					986:995	moderation	986:995	moderation of enzymatic properties of laccases	986:1031	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	0	40	with	Laccases	0:7	arg1	Properties					23:32	Variable Properties	14:32	Variable Properties from Different Strains of Steccherinum ochraceum	14:81	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	1	41	theme	multi-copper	129:140	arg1	oxidases					142:149	blue multi-copper oxidases	124:149	blue multi-copper oxidases	124:149	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	1	41	theme	multi-copper	129:140	arg1	Laccases					111:118	Laccases	111:118	Laccases	111:118	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	2	42	theme	fungal	266:271	arg1	strains					273:279	different fungal strains	256:279	different fungal strains	256:279	It is known that laccases from different fungal strains may vary in properties; however, the reason of this remains unclear.
31022851	0	43	theme	ochraceum	73:81	arg1	Strains					49:55	Different Strains	39:55	Different Strains of Steccherinum ochraceum	39:81	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	6	44	theme	Endo	847:850	arg1	H					852:852	Endo H	847:852	Endo H	847:852	After the deglycosylation of four selected laccases by Endo H and PNGase F, their affinities to pyrocatechol and ABTS became the same, suggesting a substantial role of N-linked glycosylation in moderation of enzymatic properties of laccases.
31022851	2	45	theme	different	256:264	arg1	strains					273:279	different fungal strains	256:279	different fungal strains	256:279	It is known that laccases from different fungal strains may vary in properties; however, the reason of this remains unclear.
31022851	1	46	theme	industrial	200:209	arg1	applications					211:222	potential industrial applications	190:222	potential industrial applications	190:222	Laccases are blue multi-copper oxidases with an extensive number of actual and potential industrial applications.
31022851	4	47	theme	molecular	609:617	arg1	weights					619:625	their molecular weights	603:625	their molecular weights	603:625	Although all seven laccases had the same primary sequences, there was a little variation in their molecular weights and thermostabilities.
31022851	0	48	theme	Steccherinum	60:71	arg1	ochraceum					73:81	Steccherinum ochraceum	60:81	Steccherinum ochraceum	60:81	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	0	49	dep	Laccases	0:7	arg1	Does					84:87	Does	84:87	Does	84:87	Laccases with Variable Properties from Different Strains of Steccherinum ochraceum: Does Glycosylation Matter?
31022851	5	50	theme	phenolic	748:755	arg1	substrates					757:766	phenolic substrates	748:766	phenolic substrates	748:766	Moreover, statistically significant differences in laccases' catalytic parameters of oxidation of phenolic substrates and ABTS were observed.
30305605	4	0	theme	Tn	671:672	arg1	proteins					691:698	Tn antigen-modified proteins	671:698	Tn antigen-modified proteins from Cosmc-KO pancreatic lysates	671:731	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	6	1	theme	maturity-onset	969:982	arg1	diabetes					984:991	maturity-onset diabetes	969:991	maturity-onset diabetes of the young type 8 (MODY8)	969:1019	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	0	2	theme	MODY8-like	81:90	arg1	diabetes					92:99	MODY8-like diabetes	81:99	MODY8-like diabetes in mice	81:107	Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice.
30305605	6	3	theme	diabetes	1046:1053	arg1	syndrome					1034:1041	a monogenic syndrome	1022:1041	a monogenic syndrome of diabetes	1022:1053	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	6	3	theme	diabetes	1046:1053	arg1	dysfunction					1079:1089	pancreatic exocrine dysfunction	1059:1089	pancreatic exocrine dysfunction	1059:1089	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	6	3	theme	diabetes	1046:1053	arg1	diabetes					984:991	maturity-onset diabetes	969:991	maturity-onset diabetes of the young type 8 (MODY8)	969:1019	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	1	4	theme	specific	156:163	arg1	chaperone					175:183	a specific molecular chaperone	154:183	a specific molecular chaperone assisting the folding and stability of core 1 synthase	154:238	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	1	4	theme	specific	156:163	arg1	Cosmc					110:114	Cosmc	110:114	Cosmc	110:114	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	5	5	theme	carboxyl-ester	873:886	arg1	lipase					888:893	also denoted carboxyl-ester lipase	860:893	also denoted carboxyl-ester lipase	860:893	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	5	theme	carboxyl-ester	873:886	arg1	lipase					852:857	bile salt-activated lipase	832:857	bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel)	832:899	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	6	6	theme	young	1000:1004	arg1	type					1006:1009	the young type 8	996:1011	the young type 8 (MODY8)	996:1019	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	6	6	theme	young	1000:1004	arg1	MODY8					1014:1018	MODY8	1014:1018	MODY8	1014:1018	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	8	7	theme	endocrine	1318:1326	arg1	function					1339:1346	normal exocrine and endocrine pancreatic function	1298:1346	normal exocrine and endocrine pancreatic function	1298:1346	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	3	8	theme	decreased	507:515	arg1	activities					517:526	decreased activities	507:526	decreased activities of digestive enzymes and diabetes	507:560	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	3	9	theme	enzymes	541:547	arg1	activities					517:526	decreased activities	507:526	decreased activities of digestive enzymes and diabetes	507:560	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	8	10	theme	pancreatic	1328:1337	arg1	function					1339:1346	normal exocrine and endocrine pancreatic function	1298:1346	normal exocrine and endocrine pancreatic function	1298:1346	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	3	11	with	insufficiency	488:500	arg1	activities					517:526	decreased activities	507:526	decreased activities of digestive enzymes and diabetes	507:560	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	8	12	theme	exocrine	1305:1312	arg1	function					1339:1346	normal exocrine and endocrine pancreatic function	1298:1346	normal exocrine and endocrine pancreatic function	1298:1346	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	6	13	theme	pancreatic	1059:1068	arg1	dysfunction					1079:1089	pancreatic exocrine dysfunction	1059:1089	pancreatic exocrine dysfunction	1059:1089	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	7	14	theme	O-glycosylated	1145:1158	arg1	Cel					1160:1162	differentially O-glycosylated Cel	1130:1162	differentially O-glycosylated Cel	1130:1162	Here, we provide data suggesting that differentially O-glycosylated Cel could negatively affect beta cell function.
30305605	3	15	from	ablation	349:356	arg1	pancreas					383:390	the exocrine pancreas	370:390	the exocrine pancreas of mice	370:398	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	6	16	theme	monogenic	1024:1032	arg1	syndrome					1034:1041	a monogenic syndrome	1022:1041	a monogenic syndrome of diabetes	1022:1053	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	2	17	theme	crucial	258:264	arg1	role					266:269	a crucial role	256:269	a crucial role	256:269	Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins.
30305605	1	18	theme	molecular	165:173	arg1	chaperone					175:183	a specific molecular chaperone	154:183	a specific molecular chaperone assisting the folding and stability of core 1 synthase	154:238	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	1	18	theme	molecular	165:173	arg1	Cosmc					110:114	Cosmc	110:114	Cosmc	110:114	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	3	19	theme	exocrine	374:381	arg1	pancreas					383:390	the exocrine pancreas	370:390	the exocrine pancreas of mice	370:398	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	5	20	theme	proteins	797:804	arg1	proteins					797:804	proteins	797:804	proteins	797:804	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	20	theme	proteins	797:804	arg1	variety					786:792	a variety	784:792	a variety of proteins	784:804	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	8	21	theme	O-glycan	1275:1282	arg1	formation					1284:1292	correct O-glycan formation	1267:1292	correct O-glycan formation	1267:1292	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	7	22	theme	beta	1188:1191	arg1	function					1198:1205	beta cell function	1188:1205	beta cell function	1188:1205	Here, we provide data suggesting that differentially O-glycosylated Cel could negatively affect beta cell function.
30305605	2	23	theme	O-linked	294:301	arg1	glycosylation					303:315	O-linked glycosylation	294:315	O-linked glycosylation of proteins	294:327	Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins.
30305605	4	24	theme	villosa	642:648	arg1	agglutinin					650:659	Vicia villosa agglutinin	636:659	Vicia villosa agglutinin	636:659	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	3	25	theme	Cosmc	361:365	arg1	ablation					349:356	ablation	349:356	ablation of Cosmc in the exocrine pancreas of mice	349:398	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	5	26	dep	lipase	888:893	arg1	Cel					896:898	Cel	896:898	Cel	896:898	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	4	27	from	lysates	725:731	arg1	proteins					691:698	Tn antigen-modified proteins	671:698	Tn antigen-modified proteins from Cosmc-KO pancreatic lysates	671:731	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	4	28	theme	pancreatic	714:723	arg1	lysates					725:731	Cosmc-KO pancreatic lysates	705:731	Cosmc-KO pancreatic lysates	705:731	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	3	29	theme	mice	395:398	arg1	pancreas					383:390	the exocrine pancreas	370:390	the exocrine pancreas of mice	370:398	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	0	30	theme	O-glycosylation	16:30	arg1	Loss					0:3	Loss	0:3	Loss of complex O-glycosylation	0:30	Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice.
30305605	6	31	theme	frameshift	935:944	arg1	mutations					946:954	frameshift mutations	935:954	frameshift mutations in CEL	935:961	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	8	32	theme	correct	1267:1273	arg1	formation					1284:1292	correct O-glycan formation	1267:1292	correct O-glycan formation	1267:1292	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	8	33	theme	normal	1298:1303	arg1	function					1339:1346	normal exocrine and endocrine pancreatic function	1298:1346	normal exocrine and endocrine pancreatic function	1298:1346	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	3	34	theme	O-glycans	431:439	arg1	expression					407:416	expression	407:416	expression of truncated O-glycans (Tn antigen)	407:452	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	0	35	theme	complex	8:14	arg1	O-glycosylation					16:30	complex O-glycosylation	8:30	complex O-glycosylation	8:30	Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice.
30305605	4	36	theme	molecular	581:589	arg1	causes					591:596	the molecular causes	577:596	the molecular causes of the pleiotropic phenotype	577:625	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	0	37	from	diabetes	92:99	arg1	mice					104:107	mice	104:107	mice	104:107	Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice.
30305605	3	38	theme	digestive	531:539	arg1	enzymes					541:547	digestive enzymes	531:547	digestive enzymes	531:547	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	5	39	theme	denoted	865:871	arg1	lipase					888:893	also denoted carboxyl-ester lipase	860:893	also denoted carboxyl-ester lipase	860:893	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	39	theme	denoted	865:871	arg1	lipase					852:857	bile salt-activated lipase	832:857	bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel)	832:899	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	0	40	theme	exocrine	40:47	arg1	function					60:67	exocrine pancreatic function	40:67	exocrine pancreatic function	40:67	Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice.
30305605	4	41	theme	antigen-modified	674:689	arg1	proteins					691:698	Tn antigen-modified proteins	671:698	Tn antigen-modified proteins from Cosmc-KO pancreatic lysates	671:731	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	6	42	from	mutations	946:954	arg1	CEL					959:961	CEL	959:961	CEL	959:961	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	4	43	theme	Vicia	636:640	arg1	agglutinin					650:659	Vicia villosa agglutinin	636:659	Vicia villosa agglutinin	636:659	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	5	44	theme	which	826:830	arg1	lipase					852:857	bile salt-activated lipase	832:857	bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel)	832:899	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	44	theme	which	826:830	arg1	abundant					914:921	abundant	914:921	abundant	914:921	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	45	theme	salt-activated	837:850	arg1	lipase					888:893	also denoted carboxyl-ester lipase	860:893	also denoted carboxyl-ester lipase	860:893	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	45	theme	salt-activated	837:850	arg1	lipase					852:857	bile salt-activated lipase	832:857	bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel)	832:899	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	45	theme	salt-activated	837:850	arg1	abundant					914:921	abundant	914:921	abundant	914:921	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	46	theme	bile	832:835	arg1	lipase					888:893	also denoted carboxyl-ester lipase	860:893	also denoted carboxyl-ester lipase	860:893	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	46	theme	bile	832:835	arg1	lipase					852:857	bile salt-activated lipase	832:857	bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel)	832:899	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	5	46	theme	bile	832:835	arg1	abundant					914:921	abundant	914:921	abundant	914:921	Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant.
30305605	3	47	theme	truncated	421:429	arg1	O-glycans					431:439	truncated O-glycans	421:439	truncated O-glycans (Tn antigen)	421:452	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	3	47	theme	truncated	421:429	arg1	antigen					445:451	Tn antigen	442:451	Tn antigen	442:451	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	6	48	theme	type	1006:1009	arg1	syndrome					1034:1041	a monogenic syndrome	1022:1041	a monogenic syndrome of diabetes	1022:1053	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	6	48	theme	type	1006:1009	arg1	dysfunction					1079:1089	pancreatic exocrine dysfunction	1059:1089	pancreatic exocrine dysfunction	1059:1089	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	6	48	theme	type	1006:1009	arg1	diabetes					984:991	maturity-onset diabetes	969:991	maturity-onset diabetes of the young type 8 (MODY8)	969:1019	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	3	49	theme	diabetes	553:560	arg1	activities					517:526	decreased activities	507:526	decreased activities of digestive enzymes and diabetes	507:560	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	6	50	theme	exocrine	1070:1077	arg1	dysfunction					1079:1089	pancreatic exocrine dysfunction	1059:1089	pancreatic exocrine dysfunction	1059:1089	In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction.
30305605	8	51	theme	formation	1284:1292	arg1	importance					1253:1262	the importance	1249:1262	the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function	1249:1346	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	0	52	theme	pancreatic	49:58	arg1	function					60:67	exocrine pancreatic function	40:67	exocrine pancreatic function	40:67	Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice.
30305605	2	53	link	O-linked	294:301	arg1	glycosylation					303:315	O-linked glycosylation	294:315	O-linked glycosylation of proteins	294:327	Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins.
30305605	2	54	theme	proteins	320:327	arg1	glycosylation					303:315	O-linked glycosylation	294:315	O-linked glycosylation of proteins	294:327	Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins.
30305605	2	55	gly	glycosylation	303:315	arg1	proteins					320:327	proteins	320:327	proteins	320:327	Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins.
30305605	8	56	theme	pathogenic	1404:1413	arg1	mechanisms					1415:1424	pathogenic mechanisms	1404:1424	pathogenic mechanisms of the pancreas	1404:1440	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	4	57	used	used	631:634	arg2	we					628:629	we	628:629	we	628:629	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	3	58	theme	Tn	442:443	arg1	O-glycans					431:439	truncated O-glycans	421:439	truncated O-glycans (Tn antigen)	421:452	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	3	58	theme	Tn	442:443	arg1	antigen					445:451	Tn antigen	442:451	Tn antigen	442:451	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	8	59	theme	aberrant	1363:1370	arg1	O-glycans					1372:1380	aberrant O-glycans	1363:1380	aberrant O-glycans	1363:1380	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	1	60	theme	core	224:227	arg1	synthase					231:238	core 1 synthase	224:238	core 1 synthase	224:238	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	7	61	gly	O-glycosylated	1145:1158	arg1	Cel					1160:1162	differentially O-glycosylated Cel	1130:1162	differentially O-glycosylated Cel	1130:1162	Here, we provide data suggesting that differentially O-glycosylated Cel could negatively affect beta cell function.
30305605	8	62	theme	pancreas	1433:1440	arg1	mechanisms					1415:1424	pathogenic mechanisms	1404:1424	pathogenic mechanisms of the pancreas	1404:1440	Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
30305605	4	63	theme	proteomic	749:757	arg1	analysis					759:766	a proteomic analysis	747:766	a proteomic analysis	747:766	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	2	64	theme	glycosylation	303:315	arg1	biosynthesis					278:289	the biosynthesis	274:289	the biosynthesis of O-linked glycosylation of proteins	274:327	Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins.
30305605	4	65	theme	Cosmc-KO	705:712	arg1	lysates					725:731	Cosmc-KO pancreatic lysates	705:731	Cosmc-KO pancreatic lysates	705:731	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	7	66	theme	cell	1193:1196	arg1	function					1198:1205	beta cell function	1188:1205	beta cell function	1188:1205	Here, we provide data suggesting that differentially O-glycosylated Cel could negatively affect beta cell function.
30305605	4	67	theme	phenotype	617:625	arg1	causes					591:596	the molecular causes	577:596	the molecular causes of the pleiotropic phenotype	577:625	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	1	68	dep	folding	199:205	arg1	the					195:197	the	195:197	the	195:197	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	4	69	theme	pleiotropic	605:615	arg1	phenotype					617:625	the pleiotropic phenotype	601:625	the pleiotropic phenotype	601:625	To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis.
30305605	3	70	theme	exocrine	468:475	arg1	insufficiency					488:500	exocrine pancreatic insufficiency	468:500	exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes	468:560	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30305605	1	71	theme	synthase	231:238	arg1	stability					211:219	stability	211:219	stability	211:219	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	1	71	theme	synthase	231:238	arg1	folding					199:205	folding	199:205	folding	199:205	Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase.
30305605	3	72	theme	pancreatic	477:486	arg1	insufficiency					488:500	exocrine pancreatic insufficiency	468:500	exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes	468:560	Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes.
30285435	2	0	theme	OGT	391:393	arg1	function					395:402	OGT function	391:402	OGT function	391:402	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	1	1	gly	glycosylation	87:99	arg1	proteins					128:135	nuclear and cytoplasmic proteins	104:135	nuclear and cytoplasmic proteins	104:135	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	4	2	dep	disclosing	579:588	arg1	addition					567:574	addition	567:574	addition	567:574	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	1	3	theme	proteins	128:135	arg1	glycosylation					87:99	Reversible glycosylation	76:99	Reversible glycosylation of nuclear and cytoplasmic proteins	76:135	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	1	3	theme	proteins	128:135	arg1	mechanism					164:172	an important regulatory mechanism	140:172	an important regulatory mechanism across metazoans	140:189	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	2	4	theme	potent	342:347	arg1	inhibitors					365:374	potent, cell-permeable inhibitors	342:374	potent, cell-permeable inhibitors	342:374	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	1	5	theme	Reversible	76:85	arg1	glycosylation					87:99	Reversible glycosylation	76:99	Reversible glycosylation of nuclear and cytoplasmic proteins	76:135	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	1	5	theme	Reversible	76:85	arg1	mechanism					164:172	an important regulatory mechanism	140:172	an important regulatory mechanism across metazoans	140:189	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	2	6	link	O-linked	204:211	arg1	transferase					233:243	O-linked N-acetylglucosamine transferase	204:243	O-linked N-acetylglucosamine transferase (OGT)	204:249	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	6	link	O-linked	204:211	arg1	enzyme					196:201	One enzyme	192:201	One enzyme	192:201	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	6	link	O-linked	204:211	arg1	OGT					246:248	OGT	246:248	OGT	246:248	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	4	7	theme	enzymes	708:714	arg1	refractory					742:751	refractory	742:751	refractory	742:751	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	4	7	theme	enzymes	708:714	arg1	glycosyltransferases					674:693	glycosyltransferases	674:693	glycosyltransferases	674:693	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	4	7	theme	enzymes	708:714	arg1	family					698:703	a family	696:703	a family of enzymes that has been notoriously refractory to inhibitor development	696:776	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	1	8	theme	nuclear	104:110	arg1	proteins					128:135	nuclear and cytoplasmic proteins	104:135	nuclear and cytoplasmic proteins	104:135	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	3	9	theme	inhibitors	457:466	arg1	evolution					440:448	the structure-based evolution	420:448	the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity	420:561	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	0	10	theme	Structure-Based	0:14	arg1	Evolution					16:24	Structure-Based Evolution	0:24	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors	0:73	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
30285435	0	11	theme	Low	29:31	arg1	Inhibitors					64:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
30285435	1	12	theme	cytoplasmic	116:126	arg1	proteins					128:135	nuclear and cytoplasmic proteins	104:135	nuclear and cytoplasmic proteins	104:135	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	3	13	theme	nanomolar	502:510	arg1	potency					523:529	low nanomolar inhibitory potency	498:529	low nanomolar inhibitory potency	498:529	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	2	14	theme	O-linked	204:211	arg1	transferase					233:243	O-linked N-acetylglucosamine transferase	204:243	O-linked N-acetylglucosamine transferase (OGT)	204:249	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	14	theme	O-linked	204:211	arg1	enzyme					196:201	One enzyme	192:201	One enzyme	192:201	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	14	theme	O-linked	204:211	arg1	OGT					246:248	OGT	246:248	OGT	246:248	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	15	theme	well-known	322:331	arg1	need					333:336	a well-known need	320:336	a well-known need for potent, cell-permeable inhibitors to interrogate OGT function	320:402	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	3	16	theme	inhibitory	512:521	arg1	potency					523:529	low nanomolar inhibitory potency	498:529	low nanomolar inhibitory potency	498:529	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	0	17	theme	O-GlcNAc	43:50	arg1	Inhibitors					64:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
30285435	4	18	theme	inhibitor	756:764	arg1	development					766:776	inhibitor development	756:776	inhibitor development	756:776	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	0	19	theme	Nanomolar	33:41	arg1	Inhibitors					64:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
30285435	3	20	theme	OGT	453:455	arg1	inhibitors					457:466	OGT inhibitors	453:466	OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity	453:561	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	4	21	dep	report	631:636	arg1	provide					638:644	provide	638:644	report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development	631:776	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	3	22	theme	low	498:500	arg1	potency					523:529	low nanomolar inhibitory potency	498:529	low nanomolar inhibitory potency	498:529	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	0	23	theme	Inhibitors	64:73	arg1	Evolution					16:24	Structure-Based Evolution	0:24	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors	0:73	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
30285435	3	24	theme	on-target	535:543	arg1	activity					554:561	on-target cellular activity	535:561	on-target cellular activity	535:561	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	0	25	theme	Transferase	52:62	arg1	Inhibitors					64:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Low Nanomolar O-GlcNAc Transferase Inhibitors	29:73	Structure-Based Evolution of Low Nanomolar O-GlcNAc Transferase Inhibitors.
30285435	4	26	theme	OGT	597:599	arg1	inhibitors					601:610	useful OGT inhibitors	590:610	useful OGT inhibitors	590:610	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	4	26	theme	OGT	597:599	arg1	structures					617:626	the structures	613:626	the structures	613:626	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	3	27	theme	cellular	545:552	arg1	activity					554:561	on-target cellular activity	535:561	on-target cellular activity	535:561	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	4	28	theme	useful	590:595	arg1	inhibitors					601:610	useful OGT inhibitors	590:610	useful OGT inhibitors	590:610	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	4	28	theme	useful	590:595	arg1	structures					617:626	the structures	613:626	the structures	613:626	In addition to disclosing useful OGT inhibitors, the structures we report provide insight into how to inhibit glycosyltransferases, a family of enzymes that has been notoriously refractory to inhibitor development.
30285435	1	29	theme	important	143:151	arg1	glycosylation					87:99	Reversible glycosylation	76:99	Reversible glycosylation of nuclear and cytoplasmic proteins	76:135	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	1	29	theme	important	143:151	arg1	mechanism					164:172	an important regulatory mechanism	140:172	an important regulatory mechanism across metazoans	140:189	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	3	30	with	compounds	483:491	arg1	potency					523:529	low nanomolar inhibitory potency	498:529	low nanomolar inhibitory potency	498:529	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	3	30	with	compounds	483:491	arg1	activity					554:561	on-target cellular activity	535:561	on-target cellular activity	535:561	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
30285435	2	31	theme	nucleocytoplasmic	275:291	arg1	glycosylation					293:305	all nucleocytoplasmic glycosylation	271:305	all nucleocytoplasmic glycosylation	271:305	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	1	32	theme	regulatory	153:162	arg1	glycosylation					87:99	Reversible glycosylation	76:99	Reversible glycosylation of nuclear and cytoplasmic proteins	76:135	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	1	32	theme	regulatory	153:162	arg1	mechanism					164:172	an important regulatory mechanism	140:172	an important regulatory mechanism across metazoans	140:189	Reversible glycosylation of nuclear and cytoplasmic proteins is an important regulatory mechanism across metazoans.
30285435	2	33	dep	potent	342:347	arg1	cell-permeable					350:363	cell-permeable	350:363	cell-permeable	350:363	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	34	theme	N-acetylglucosamine	213:231	arg1	transferase					233:243	O-linked N-acetylglucosamine transferase	204:243	O-linked N-acetylglucosamine transferase (OGT)	204:249	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	34	theme	N-acetylglucosamine	213:231	arg1	enzyme					196:201	One enzyme	192:201	One enzyme	192:201	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	2	34	theme	N-acetylglucosamine	213:231	arg1	OGT					246:248	OGT	246:248	OGT	246:248	One enzyme, O-linked N-acetylglucosamine transferase (OGT), is responsible for all nucleocytoplasmic glycosylation and there is a well-known need for potent, cell-permeable inhibitors to interrogate OGT function.
30285435	3	35	theme	structure-based	424:438	arg1	evolution					440:448	the structure-based evolution	420:448	the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity	420:561	Here we report the structure-based evolution of OGT inhibitors culminating in compounds with low nanomolar inhibitory potency and on-target cellular activity.
29615517	9	0	theme	traumatic	1422:1430	arg1	injuries					1436:1443	traumatic CNS injuries	1422:1443	traumatic CNS injuries	1422:1443	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	4	1	gly	glycosylation	720:732	arg1	cells					788:792	HEK293T and Neuro2A cells	768:792	cells	788:792	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	4	1	gly	glycosylation	720:732	arg1	neurons					806:812	primary neurons	798:812	primary neurons	798:812	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	4	1	gly	glycosylation	720:732	arg1	NgR1					760:763	NgR1	760:763	NgR1	760:763	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	4	2	theme	Endogenous	606:615	arg1	ORL1					635:638	Endogenous and overexpressed ORL1	606:638	Endogenous and overexpressed ORL1	606:638	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	0	3	theme	cord	78:81	arg1	injury					83:88	spinal cord injury	71:88	spinal cord injury	71:88	The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury.
29615517	9	4	theme	ORL1	1383:1386	arg1	antagonists					1388:1398	ORL1 antagonists	1383:1398	ORL1 antagonists	1383:1398	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	1	5	theme	endogenous	154:163	arg1	inhibitors					165:174	endogenous inhibitors	154:174	endogenous inhibitors	154:174	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	8	6	theme	Ngr1	1258:1261	arg1	deletion					1263:1270	combined Ngr1 deletion	1249:1270	combined Ngr1 deletion	1249:1270	These effects were further enhanced by combined Ngr1 deletion and ORL1 inhibition.
29615517	3	7	dep	increased	497:505	arg1	encodes					542:548	encodes	542:548	encodes the receptor for the opioid-related peptide nociceptin	542:603	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	3	8	theme	opioid-related	571:584	arg1	nociceptin					594:603	the opioid-related peptide nociceptin	567:603	the opioid-related peptide nociceptin	567:603	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	4	9	theme	overexpressed	621:633	arg1	ORL1					635:638	Endogenous and overexpressed ORL1	606:638	Endogenous and overexpressed ORL1	606:638	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	4	10	theme	Neuro2A	780:786	arg1	cells					788:792	HEK293T and Neuro2A cells	768:792	cells	788:792	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	4	11	theme	primary	798:804	arg1	neurons					806:812	primary neurons	798:812	primary neurons	798:812	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	7	12	theme	cord	1119:1122	arg1	hemisection					1080:1090	dorsal hemisection	1073:1090	dorsal hemisection of the mid-thoracic spinal cord	1073:1122	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	4	13	theme	surface	738:744	arg1	expression					746:755	surface expression	738:755	surface expression of NgR1	738:763	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	1	14	theme	traumatic	111:119	arg1	injury					133:138	traumatic spinal cord injury	111:138	traumatic spinal cord injury	111:138	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	7	15	theme	raphespinal	1182:1192	arg1	sprouting					1199:1207	lumbar raphespinal axon sprouting	1175:1207	lumbar raphespinal axon sprouting	1175:1207	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	2	16	theme	compensatory	288:299	arg1	pathways					301:308	compensatory pathways	288:308	compensatory pathways	288:308	The partial repair phenotypes suggest that compensatory pathways limit improvement.
29615517	3	17	theme	regeneration	449:460	arg1	inhibitors					428:437	myelin-associated inhibitors	410:437	myelin-associated inhibitors of axonal regeneration such as Nogo	410:473	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	3	17	theme	regeneration	449:460	arg1	Nogo					470:473	Nogo	470:473	Nogo	470:473	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	1	18	theme	inhibitors	165:174	arg1	blockade					187:194	selective blockade	177:194	selective blockade	177:194	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	6	19	theme	ORL1	948:951	arg1	agonist					953:959	an ORL1 agonist	945:959	an ORL1 agonist	945:959	Furthermore, regeneration was inhibited by an ORL1 agonist and enhanced by the ORL1 antagonist J113397 through a ROCK-dependent mechanism.
29615517	7	20	theme	axon	1194:1197	arg1	sprouting					1199:1207	lumbar raphespinal axon sprouting	1175:1207	lumbar raphespinal axon sprouting	1175:1207	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	6	21	theme	ROCK-dependent	1015:1028	arg1	mechanism					1030:1038	a ROCK-dependent mechanism	1013:1038	a ROCK-dependent mechanism	1013:1038	Furthermore, regeneration was inhibited by an ORL1 agonist and enhanced by the ORL1 antagonist J113397 through a ROCK-dependent mechanism.
29615517	0	22	theme	nociceptin	4:13	arg1	receptor					15:22	The nociceptin receptor	0:22	The nociceptin receptor	0:22	The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury.
29615517	5	23	theme	ORL1	815:818	arg1	overexpression					820:833	ORL1 overexpression	815:833	ORL1 overexpression	815:833	ORL1 overexpression inhibited cortical neuron axon regeneration independently of NgR1.
29615517	0	24	theme	spinal	71:76	arg1	injury					83:88	spinal cord injury	71:88	spinal cord injury	71:88	The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury.
29615517	3	25	theme	peptide	586:592	arg1	nociceptin					594:603	the opioid-related peptide nociceptin	567:603	the opioid-related peptide nociceptin	567:603	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	1	26	theme	selective	177:185	arg1	blockade					187:194	selective blockade	177:194	selective blockade	177:194	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	8	27	theme	ORL1	1276:1279	arg1	inhibition					1281:1290	ORL1 inhibition	1276:1290	ORL1 inhibition	1276:1290	These effects were further enhanced by combined Ngr1 deletion and ORL1 inhibition.
29615517	9	28	theme	CNS	1432:1434	arg1	injuries					1436:1443	traumatic CNS injuries	1422:1443	traumatic CNS injuries	1422:1443	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	7	29	theme	lumbar	1175:1180	arg1	sprouting					1199:1207	lumbar raphespinal axon sprouting	1175:1207	lumbar raphespinal axon sprouting	1175:1207	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	7	30	theme	locomotor	1142:1150	arg1	function					1152:1159	greater locomotor function	1134:1159	greater locomotor function	1134:1159	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	1	31	theme	Axonal	91:96	arg1	growth					98:103	Axonal growth	91:103	Axonal growth after traumatic spinal cord injury	91:138	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	9	32	theme	neural	1311:1316	arg1	repair					1318:1323	neural repair	1311:1323	neural repair	1311:1323	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	5	33	theme	cortical	845:852	arg1	regeneration					866:877	cortical neuron axon regeneration	845:877	cortical neuron axon regeneration	845:877	ORL1 overexpression inhibited cortical neuron axon regeneration independently of NgR1.
29615517	9	34	from	recovery	1408:1415	arg1	mice					1472:1475	wild-type and Ngr1 null mice	1448:1475	wild-type and Ngr1 null mice	1448:1475	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	0	35	from	injury	83:88	arg1	regeneration					40:51	axonal regeneration	33:51	axonal regeneration	33:51	The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury.
29615517	0	35	from	injury	83:88	arg1	recovery					57:64	recovery	57:64	recovery	57:64	The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury.
29615517	3	36	theme	ORL1	530:533	arg1	expression					516:525	the mRNA expression	507:525	the mRNA expression of ORL1	507:533	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	4	37	theme	NgR1	675:678	arg1	protein					680:686	immature NgR1 protein	666:686	immature NgR1 protein	666:686	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	4	38	theme	O-linked	711:718	arg1	glycosylation					720:732	the O-linked glycosylation	707:732	the O-linked glycosylation	707:732	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	7	39	theme	greater	1134:1140	arg1	function					1152:1159	greater locomotor function	1134:1159	greater locomotor function	1134:1159	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	3	40	from	Ngr1	375:378	arg1	deficient					362:370	deficient	362:370	deficient	362:370	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	4	41	link	O-linked	711:718	arg1	glycosylation					720:732	the O-linked glycosylation	707:732	the O-linked glycosylation	707:732	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	0	42	theme	axonal	33:38	arg1	regeneration					40:51	axonal regeneration	33:51	axonal regeneration	33:51	The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury.
29615517	3	43	theme	axonal	442:447	arg1	regeneration					449:460	axonal regeneration	442:460	axonal regeneration	442:460	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	1	44	theme	partial	214:220	arg1	recovery					235:242	partial neurological recovery	214:242	partial neurological recovery	214:242	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	3	45	theme	myelin-associated	410:426	arg1	inhibitors					428:437	myelin-associated inhibitors	410:437	myelin-associated inhibitors of axonal regeneration such as Nogo	410:473	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	3	45	theme	myelin-associated	410:426	arg1	Nogo					470:473	Nogo	470:473	Nogo	470:473	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	9	46	theme	Ngr1	1462:1465	arg1	mice					1472:1475	wild-type and Ngr1 null mice	1448:1475	wild-type and Ngr1 null mice	1448:1475	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	3	47	theme	Gene	329:332	arg1	profiles					345:352	Gene expression profiles	329:352	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo,	329:474	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	7	48	theme	mid-thoracic	1099:1110	arg1	cord					1119:1122	the mid-thoracic spinal cord	1095:1122	the mid-thoracic spinal cord	1095:1122	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	3	49	theme	mRNA	511:514	arg1	expression					516:525	the mRNA expression	507:525	the mRNA expression of ORL1	507:533	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	5	50	theme	neuron	854:859	arg1	regeneration					866:877	cortical neuron axon regeneration	845:877	cortical neuron axon regeneration	845:877	ORL1 overexpression inhibited cortical neuron axon regeneration independently of NgR1.
29615517	9	51	theme	null	1467:1470	arg1	mice					1472:1475	wild-type and Ngr1 null mice	1448:1475	wild-type and Ngr1 null mice	1448:1475	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	3	52	theme	expression	334:343	arg1	profiles					345:352	Gene expression profiles	329:352	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo,	329:474	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	7	53	theme	dorsal	1073:1078	arg1	hemisection					1080:1090	dorsal hemisection	1073:1090	dorsal hemisection of the mid-thoracic spinal cord	1073:1122	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	1	54	theme	spinal	121:126	arg1	injury					133:138	traumatic spinal cord injury	111:138	traumatic spinal cord injury	111:138	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	6	55	theme	antagonist	986:995	arg1	J113397					997:1003	the ORL1 antagonist J113397	977:1003	the ORL1 antagonist J113397	977:1003	Furthermore, regeneration was inhibited by an ORL1 agonist and enhanced by the ORL1 antagonist J113397 through a ROCK-dependent mechanism.
29615517	4	56	theme	NgR1	760:763	arg1	glycosylation					720:732	the O-linked glycosylation	707:732	the O-linked glycosylation	707:732	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	4	56	theme	NgR1	760:763	arg1	expression					746:755	surface expression	738:755	surface expression of NgR1	738:763	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	9	57	theme	wild-type	1448:1456	arg1	mice					1472:1475	wild-type and Ngr1 null mice	1448:1475	wild-type and Ngr1 null mice	1448:1475	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	1	58	theme	cord	128:131	arg1	injury					133:138	traumatic spinal cord injury	111:138	traumatic spinal cord injury	111:138	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	1	59	theme	neurological	222:233	arg1	recovery					235:242	partial neurological recovery	214:242	partial neurological recovery	214:242	Axonal growth after traumatic spinal cord injury is limited by endogenous inhibitors, selective blockade of which promotes partial neurological recovery.
29615517	7	60	theme	spinal	1112:1117	arg1	cord					1119:1122	the mid-thoracic spinal cord	1095:1122	the mid-thoracic spinal cord	1095:1122	Mice treated with J113397 after dorsal hemisection of the mid-thoracic spinal cord recovered greater locomotor function and exhibited lumbar raphespinal axon sprouting.
29615517	9	61	theme	NgR1	1362:1365	arg1	maturation					1367:1376	NgR1 maturation	1362:1376	NgR1 maturation	1362:1376	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	4	62	theme	HEK293T	768:774	arg1	cells					788:792	HEK293T and Neuro2A cells	768:792	cells	788:792	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	3	63	theme	mice	357:360	arg1	profiles					345:352	Gene expression profiles	329:352	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo,	329:474	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	3	64	from	deficient	362:370	arg1	receptor					397:404	a receptor	395:404	a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo	395:473	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	3	64	from	deficient	362:370	arg1	Ngr1					375:378	Ngr1	375:378	Ngr1	375:378	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	2	65	theme	repair	257:262	arg1	phenotypes					264:273	The partial repair phenotypes	245:273	The partial repair phenotypes	245:273	The partial repair phenotypes suggest that compensatory pathways limit improvement.
29615517	9	66	from	injuries	1436:1443	arg1	recovery					1408:1415	recovery	1408:1415	recovery from traumatic CNS injuries in wild-type and Ngr1 null mice	1408:1475	Thus, ORL1 limits neural repair directly and indirectly by enhancing NgR1 maturation, and ORL1 antagonists enhance recovery from traumatic CNS injuries in wild-type and Ngr1 null mice.
29615517	4	67	theme	immature	666:673	arg1	protein					680:686	immature NgR1 protein	666:686	immature NgR1 protein	666:686	Endogenous and overexpressed ORL1 coimmunoprecipitated with immature NgR1 protein, and ORL1 enhanced the O-linked glycosylation and surface expression of NgR1 in HEK293T and Neuro2A cells and primary neurons.
29615517	3	68	theme	deficient	362:370	arg1	mice					357:360	mice	357:360	mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo,	357:474	Gene expression profiles of mice deficient in Ngr1, which encodes a receptor for myelin-associated inhibitors of axonal regeneration such as Nogo, revealed that trauma increased the mRNA expression of ORL1, which encodes the receptor for the opioid-related peptide nociceptin.
29615517	6	69	theme	ORL1	981:984	arg1	J113397					997:1003	the ORL1 antagonist J113397	977:1003	the ORL1 antagonist J113397	977:1003	Furthermore, regeneration was inhibited by an ORL1 agonist and enhanced by the ORL1 antagonist J113397 through a ROCK-dependent mechanism.
29615517	2	70	theme	partial	249:255	arg1	phenotypes					264:273	The partial repair phenotypes	245:273	The partial repair phenotypes	245:273	The partial repair phenotypes suggest that compensatory pathways limit improvement.
29615517	5	71	theme	axon	861:864	arg1	regeneration					866:877	cortical neuron axon regeneration	845:877	cortical neuron axon regeneration	845:877	ORL1 overexpression inhibited cortical neuron axon regeneration independently of NgR1.
29615517	8	72	theme	combined	1249:1256	arg1	deletion					1263:1270	combined Ngr1 deletion	1249:1270	combined Ngr1 deletion	1249:1270	These effects were further enhanced by combined Ngr1 deletion and ORL1 inhibition.
30940748	8	0	theme	proliferation	1162:1174	arg1	inhibition					1124:1133	inhibition	1124:1133	inhibition of protein synthesis, cell proliferation, and soft agar colony formation	1124:1206	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	7	1	theme	poly	1064:1067	arg1	mRNA					1072:1075	poly(A) mRNA	1064:1075	poly(A) mRNA	1064:1075	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	9	2	theme	protein	1322:1328	arg1	synthesis					1330:1338	fine-tune protein synthesis	1312:1338	fine-tune protein synthesis	1312:1338	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	0	3	theme	protein	85:91	arg1	synthesis					93:101	protein synthesis	85:101	protein synthesis	85:101	O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis.
30940748	4	4	theme	translation	523:533	arg1	initiation					535:544	translation initiation	523:544	translation initiation	523:544	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	10	5	theme	complexity	1442:1451	arg1	dimension					1429:1437	another dimension	1421:1437	another dimension of complexity	1421:1451	Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.
30940748	9	6	theme	eIF4G	1253:1257	arg1	glycosylation					1226:1238	The differential glycosylation	1209:1238	The differential glycosylation of eIF4A and eIF4G	1209:1257	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	9	7	theme	fine-tune	1312:1320	arg1	synthesis					1330:1338	fine-tune protein synthesis	1312:1338	fine-tune protein synthesis	1312:1338	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	10	8	theme	translational	1456:1468	arg1	control					1470:1476	translational control	1456:1476	translational control of cellular proteins	1456:1497	Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.
30940748	6	9	theme	eIF4A	858:862	arg1	activity					846:853	the duplex unwinding activity	825:853	the duplex unwinding activity of eIF4A	825:862	In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation.
30940748	7	10	theme	eIF4G	984:988	arg1	O-GlcNAcylation					965:979	site-specific O-GlcNAcylation	951:979	site-specific O-GlcNAcylation of eIF4G on Ser61	951:997	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	3	11	theme	number	369:374	arg1	development					336:346	development	336:346	development	336:346	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	3	11	theme	number	369:374	arg1	progression					352:362	progression	352:362	progression	352:362	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	4	12	theme	O-linked	463:470	arg1	β-N-acetyl-glucosamine					472:493	O-linked β-N-acetyl-glucosamine	463:493	O-linked β-N-acetyl-glucosamine (O-GlcNAcylation)	463:511	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	12	theme	O-linked	463:470	arg1	O-GlcNAcylation					496:510	O-GlcNAcylation	496:510	O-GlcNAcylation	496:510	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	5	13	theme	site-specific	631:643	arg1	O-GlcNAcylation					645:659	site-specific O-GlcNAcylation	631:659	site-specific O-GlcNAcylation of eIF4A on Ser322/323	631:682	Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G.
30940748	8	14	theme	agar	1186:1189	arg1	formation					1198:1206	soft agar colony formation	1181:1206	soft agar colony formation	1181:1206	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	10	15	theme	synthesis	1401:1409	arg1	understanding					1376:1388	the current understanding	1364:1388	the current understanding of protein synthesis	1364:1409	Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.
30940748	8	16	theme	soft	1181:1184	arg1	formation					1198:1206	soft agar colony formation	1181:1206	soft agar colony formation	1181:1206	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	4	17	dep	factors	575:581	arg1	factors					575:581	core initiation factors	559:581	core initiation factors eIF4A and eIF4G	559:597	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	17	dep	factors	575:581	arg1	eIF4G					593:597	eIF4G	593:597	eIF4G	593:597	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	17	dep	factors	575:581	arg1	eIF4A					583:587	eIF4A	583:587	eIF4A	583:587	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	5	18	theme	eIF4A	664:668	arg1	O-GlcNAcylation					645:659	site-specific O-GlcNAcylation	631:659	site-specific O-GlcNAcylation of eIF4A on Ser322/323	631:682	Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G.
30940748	9	19	theme	differential	1213:1224	arg1	glycosylation					1226:1238	The differential glycosylation	1209:1238	The differential glycosylation of eIF4A and eIF4G	1209:1257	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	8	20	theme	colony	1191:1196	arg1	formation					1198:1206	soft agar colony formation	1181:1206	soft agar colony formation	1181:1206	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	10	21	theme	current	1368:1374	arg1	understanding					1376:1388	the current understanding	1364:1388	the current understanding of protein synthesis	1364:1409	Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.
30940748	4	22	link	O-linked	463:470	arg1	β-N-acetyl-glucosamine					472:493	O-linked β-N-acetyl-glucosamine	463:493	O-linked β-N-acetyl-glucosamine (O-GlcNAcylation)	463:511	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	22	link	O-linked	463:470	arg1	O-GlcNAcylation					496:510	O-GlcNAcylation	496:510	O-GlcNAcylation	496:510	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	8	23	theme	formation	1198:1206	arg1	inhibition					1124:1133	inhibition	1124:1133	inhibition of protein synthesis, cell proliferation, and soft agar colony formation	1124:1206	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	8	24	theme	cell	1157:1160	arg1	proliferation					1162:1174	cell proliferation	1157:1174	cell proliferation	1157:1174	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	10	25	theme	proteins	1490:1497	arg1	control					1470:1476	translational control	1456:1476	translational control of cellular proteins	1456:1497	Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.
30940748	6	26	theme	unwinding	836:844	arg1	activity					846:853	the duplex unwinding activity	825:853	the duplex unwinding activity of eIF4A	825:862	In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation.
30940748	3	27	theme	protein	281:287	arg1	synthesis					289:297	protein synthesis	281:297	protein synthesis	281:297	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	10	28	theme	cellular	1481:1488	arg1	proteins					1490:1497	cellular proteins	1481:1497	cellular proteins	1481:1497	Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.
30940748	6	29	theme	duplex	829:834	arg1	activity					846:853	the duplex unwinding activity	825:853	the duplex unwinding activity of eIF4A	825:862	In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation.
30940748	1	30	theme	Protein	104:110	arg1	synthesis					112:120	Protein synthesis	104:120	Protein synthesis	104:120	Protein synthesis is essential for cell growth, proliferation, and survival.
30940748	4	31	theme	dynamic	427:433	arg1	modification					435:446	the dynamic modification	423:446	the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation)	423:511	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	0	32	theme	components	24:33	arg1	O-GlcNAcylation					0:14	O-GlcNAcylation	0:14	O-GlcNAcylation of core components of the translation initiation machinery	0:73	O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis.
30940748	4	33	theme	initiation	564:573	arg1	factors					575:581	core initiation factors	559:581	core initiation factors eIF4A and eIF4G	559:597	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	33	theme	initiation	564:573	arg1	eIF4G					593:597	eIF4G	593:597	eIF4G	593:597	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	33	theme	initiation	564:573	arg1	eIF4A					583:587	eIF4A	583:587	eIF4A	583:587	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	8	34	theme	eIF4G	1091:1095	arg1	O-GlcNAcylation					1097:1111	eIF4G O-GlcNAcylation	1091:1111	eIF4G O-GlcNAcylation	1091:1111	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	9	35	theme	eIF4A	1243:1247	arg1	glycosylation					1226:1238	The differential glycosylation	1209:1238	The differential glycosylation of eIF4A and eIF4G	1209:1257	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	7	36	from	O-GlcNAcylation	965:979	arg1	Ser61					993:997	Ser61	993:997	Ser61	993:997	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	3	37	theme	diseases	379:386	arg1	cancer					397:402	cancer	397:402	cancer	397:402	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	3	37	theme	diseases	379:386	arg1	number					369:374	a number	367:374	a number of diseases, such as cancer	367:402	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	6	38	theme	cell	918:921	arg1	proliferation					923:935	decreased cell proliferation	908:935	decreased cell proliferation	908:935	In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation.
30940748	5	39	with	interaction	763:773	arg1	eIF4G					780:784	eIF4G	780:784	eIF4G	780:784	Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G.
30940748	9	40	gly	glycosylation	1226:1238	arg1	eIF4G					1253:1257	eIF4G	1253:1257	eIF4G	1253:1257	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	9	40	gly	glycosylation	1226:1238	arg1	complex					1301:1307	the initiation complex	1286:1307	the initiation complex	1286:1307	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	9	40	gly	glycosylation	1226:1238	arg1	eIF4A					1243:1247	eIF4A	1243:1247	eIF4A	1243:1247	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	3	41	dep	development	336:346	arg1	the					332:334	the	332:334	the	332:334	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	2	42	theme	Protein	181:187	arg1	process					222:228	a tightly regulated process	202:228	a tightly regulated process that involves multiple mechanisms	202:262	Protein synthesis is a tightly regulated process that involves multiple mechanisms.
30940748	2	42	theme	Protein	181:187	arg1	synthesis					189:197	Protein synthesis	181:197	Protein synthesis	181:197	Protein synthesis is a tightly regulated process that involves multiple mechanisms.
30940748	2	43	theme	multiple	244:251	arg1	mechanisms					253:262	multiple mechanisms	244:262	multiple mechanisms	244:262	Protein synthesis is a tightly regulated process that involves multiple mechanisms.
30940748	3	44	theme	synthesis	289:297	arg1	Deregulation					265:276	Deregulation	265:276	Deregulation of protein synthesis	265:297	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	3	44	theme	synthesis	289:297	arg1	factor					322:327	a key factor	316:327	a key factor in the development and progression of a number of diseases, such as cancer	316:402	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	4	45	theme	proteins	451:458	arg1	modification					435:446	the dynamic modification	423:446	the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation)	423:511	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	0	46	theme	initiation	54:63	arg1	machinery					65:73	the translation initiation machinery	38:73	the translation initiation machinery	38:73	O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis.
30940748	7	47	with	interaction	1012:1022	arg1	mRNA					1072:1075	poly(A) mRNA	1064:1075	poly(A) mRNA	1064:1075	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	7	47	with	interaction	1012:1022	arg1	PABP					1054:1057	PABP	1054:1057	PABP	1054:1057	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	7	47	with	interaction	1012:1022	arg1	protein					1045:1051	poly(A)-binding protein	1029:1051	poly(A)-binding protein (PABP)	1029:1058	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	3	48	theme	key	318:320	arg1	Deregulation					265:276	Deregulation	265:276	Deregulation of protein synthesis	265:297	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	3	48	theme	key	318:320	arg1	factor					322:327	a key factor	316:327	a key factor in the development and progression of a number of diseases, such as cancer	316:402	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	8	49	theme	synthesis	1146:1154	arg1	inhibition					1124:1133	inhibition	1124:1133	inhibition of protein synthesis, cell proliferation, and soft agar colony formation	1124:1206	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	8	50	theme	protein	1138:1144	arg1	synthesis					1146:1154	protein synthesis	1138:1154	protein synthesis	1138:1154	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	0	51	theme	translation	42:52	arg1	machinery					65:73	the translation initiation machinery	38:73	the translation initiation machinery	38:73	O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis.
30940748	4	52	theme	core	559:562	arg1	factors					575:581	core initiation factors	559:581	core initiation factors eIF4A and eIF4G	559:597	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	52	theme	core	559:562	arg1	eIF4G					593:597	eIF4G	593:597	eIF4G	593:597	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	4	52	theme	core	559:562	arg1	eIF4A					583:587	eIF4A	583:587	eIF4A	583:587	Here we show that the dynamic modification of proteins by O-linked β-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively.
30940748	5	53	theme	translation	714:724	arg1	complex					737:743	the translation initiation complex	710:743	the translation initiation complex	710:743	Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G.
30940748	2	54	theme	regulated	212:220	arg1	process					222:228	a tightly regulated process	202:228	a tightly regulated process that involves multiple mechanisms	202:262	Protein synthesis is a tightly regulated process that involves multiple mechanisms.
30940748	2	54	theme	regulated	212:220	arg1	synthesis					189:197	Protein synthesis	181:197	Protein synthesis	181:197	Protein synthesis is a tightly regulated process that involves multiple mechanisms.
30940748	5	55	theme	initiation	726:735	arg1	complex					737:743	the translation initiation complex	710:743	the translation initiation complex	710:743	Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G.
30940748	6	56	theme	protein	885:891	arg1	synthesis					893:901	impaired protein synthesis	876:901	impaired protein synthesis	876:901	In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation.
30940748	1	57	theme	cell	139:142	arg1	growth					144:149	cell growth	139:149	cell growth	139:149	Protein synthesis is essential for cell growth, proliferation, and survival.
30940748	5	58	theme	complex	737:743	arg1	formation					697:705	the formation	693:705	the formation of the translation initiation complex	693:743	Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G.
30940748	6	59	theme	impaired	876:883	arg1	synthesis					893:901	impaired protein synthesis	876:901	impaired protein synthesis	876:901	In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation.
30940748	10	60	theme	protein	1393:1399	arg1	synthesis					1401:1409	protein synthesis	1393:1409	protein synthesis	1393:1409	Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins.
30940748	6	61	theme	decreased	908:916	arg1	proliferation					923:935	decreased cell proliferation	908:935	decreased cell proliferation	908:935	In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation.
30940748	7	62	theme	-binding	1036:1043	arg1	PABP					1054:1057	PABP	1054:1057	PABP	1054:1057	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	7	62	theme	-binding	1036:1043	arg1	protein					1045:1051	poly(A)-binding protein	1029:1051	poly(A)-binding protein (PABP)	1029:1058	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	7	63	theme	site-specific	951:963	arg1	O-GlcNAcylation					965:979	site-specific O-GlcNAcylation	951:979	site-specific O-GlcNAcylation of eIF4G on Ser61	951:997	In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA.
30940748	0	64	theme	machinery	65:73	arg1	components					24:33	core components	19:33	core components of the translation initiation machinery	19:73	O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis.
30940748	9	65	theme	initiation	1290:1299	arg1	complex					1301:1307	the initiation complex	1286:1307	the initiation complex	1286:1307	The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis.
30940748	0	66	theme	core	19:22	arg1	components					24:33	core components	19:33	core components of the translation initiation machinery	19:73	O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis.
30940748	5	67	from	O-GlcNAcylation	645:659	arg1	Ser322/323					673:682	Ser322/323	673:682	Ser322/323	673:682	Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G.
30940748	8	68	theme	O-GlcNAcylation	1097:1111	arg1	Depletion					1078:1086	Depletion	1078:1086	Depletion of eIF4G O-GlcNAcylation	1078:1111	Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation.
30940748	3	69	from	factor	322:327	arg1	development					336:346	development	336:346	development	336:346	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30940748	3	69	from	factor	322:327	arg1	progression					352:362	progression	352:362	progression	352:362	Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer.
30723162	0	0	theme	sialidase	80:88	arg1	activity					90:97	sialidase activity	80:97	sialidase activity in the vaginal bacterium Gardnerella vaginalis	80:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	10	1	contain	had	1700:1702	arg2	sensitivity					1708:1718	81% sensitivity	1704:1718	81% sensitivity	1704:1718	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	10	1	contain	had	1700:1702	arg1	PCRs					1648:1651	PCRs	1648:1651	PCRs of nanH2 or nanH3 from human vaginal specimens	1648:1698	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	10	1	contain	had	1700:1702	arg2	specificity					1728:1738	78% specificity	1724:1738	78% specificity	1724:1738	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	9	2	theme	vaginal	1603:1609	arg1	specimens					1611:1619	human vaginal specimens	1597:1619	human vaginal specimens of women with BV	1597:1636	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	5	3	contain	had	845:847	arg2	activity					857:864	limited activity	849:864	limited activity against synthetic and mucosal substrates	849:905	In contrast, recombinant NanH1 had limited activity against synthetic and mucosal substrates under the conditions tested.
30723162	5	3	contain	had	845:847	arg1	NanH1					839:843	recombinant NanH1	827:843	recombinant NanH1	827:843	In contrast, recombinant NanH1 had limited activity against synthetic and mucosal substrates under the conditions tested.
30723162	3	4	theme	sialidase	480:488	arg1	gene					492:495	the sialidase A gene	476:495	the sialidase A gene	476:495	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	1	5	theme	reproductive	246:257	arg1	health					259:264	adverse reproductive health	238:264	adverse reproductive health	238:264	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	8	6	located	present	1247:1253	arg2	both					1237:1240	both	1237:1240	both	1237:1240	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	6	located	present	1247:1253	arg1	strains					1284:1290	all 15 sialidase-positive strains	1258:1290	all 15 sialidase-positive strains	1258:1290	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	6	located	present	1247:1253	arg2	nanH3					1227:1231	nanH3	1227:1231	nanH3	1227:1231	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	6	located	present	1247:1253	arg2	nanH2					1220:1224	nanH2	1220:1224	nanH2	1220:1224	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	7	theme	G.	1197:1198	arg1	isolates					1210:1217	34 G. vaginalis isolates	1194:1217	34 G. vaginalis isolates	1194:1217	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	3	8	theme	A	490:490	arg1	gene					492:495	the sialidase A gene	476:495	the sialidase A gene	476:495	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	8	9	from	isolates	1334:1341	arg1	absent					1296:1301	absent	1296:1301	absent	1296:1301	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	1	10	from	abundant	172:179	arg1	vaginosis					194:202	bacterial vaginosis	184:202	bacterial vaginosis (BV)	184:207	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	1	10	from	abundant	172:179	arg1	condition					212:220	a condition	210:220	a condition associated with adverse reproductive health	210:264	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	1	10	from	abundant	172:179	arg1	BV					205:206	BV	205:206	BV	205:206	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	2	11	theme	diagnostic	291:300	arg1	activity					277:284	Sialidase activity	267:284	Sialidase activity	267:284	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	2	11	theme	diagnostic	291:300	arg1	feature					302:308	a diagnostic feature	289:308	a diagnostic feature of BV	289:314	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	10	12	theme	%	1706:1706	arg1	sensitivity					1708:1718	81% sensitivity	1704:1718	81% sensitivity	1704:1718	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	9	13	theme	women	1624:1628	arg1	specimens					1611:1619	human vaginal specimens	1597:1619	human vaginal specimens of women with BV	1597:1636	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	8	14	from	present	1247:1253	arg1	strains					1284:1290	all 15 sialidase-positive strains	1258:1290	all 15 sialidase-positive strains	1258:1290	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	10	15	theme	Lactobacillus	1766:1778	arg1	dominance					1780:1788	Lactobacillus dominance	1766:1788	Lactobacillus dominance	1766:1788	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	9	16	with	women	1624:1628	arg1	BV					1635:1636	BV	1635:1636	BV	1635:1636	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	0	17	theme	vaginal	106:112	arg1	bacterium					114:122	the vaginal bacterium Gardnerella vaginalis	102:144	the vaginal bacterium Gardnerella vaginalis	102:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	10	18	theme	nanH2	1656:1660	arg1	PCRs					1648:1651	PCRs	1648:1651	PCRs of nanH2 or nanH3 from human vaginal specimens	1648:1698	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	5	19	theme	mucosal	888:894	arg1	substrates					896:905	synthetic and mucosal substrates	874:905	synthetic and mucosal substrates	874:905	In contrast, recombinant NanH1 had limited activity against synthetic and mucosal substrates under the conditions tested.
30723162	7	20	theme	more	1123:1126	arg1	Neu5,9Ac2					1128:1136	significantly more Neu5,9Ac2	1109:1136	significantly more Neu5,9Ac2 than strains encoding only NanH3	1109:1169	Similarly, G. vaginalis strains encoding NanH2 cleaved and foraged significantly more Neu5,9Ac2 than strains encoding only NanH3.
30723162	4	21	theme	mucosal	794:800	arg1	substrates					802:811	relevant mucosal substrates	785:811	relevant mucosal substrates	785:811	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	4	22	theme	α2-3-	723:727	arg1	N-					745:746	α2-3- and α2-6-linked N-	723:746	α2-3- and α2-6-linked N-	723:746	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	1	23	theme	bacterial	184:192	arg1	vaginosis					194:202	bacterial vaginosis	184:202	bacterial vaginosis (BV)	184:207	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	1	23	theme	bacterial	184:192	arg1	condition					212:220	a condition	210:220	a condition associated with adverse reproductive health	210:264	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	1	23	theme	bacterial	184:192	arg1	BV					205:206	BV	205:206	BV	205:206	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	7	24	theme	only	1160:1163	arg1	NanH3					1165:1169	only NanH3	1160:1169	only NanH3	1160:1169	Similarly, G. vaginalis strains encoding NanH2 cleaved and foraged significantly more Neu5,9Ac2 than strains encoding only NanH3.
30723162	7	25	theme	G.	1053:1054	arg1	strains					1066:1072	G. vaginalis strains	1053:1072	G. vaginalis strains encoding NanH2	1053:1087	Similarly, G. vaginalis strains encoding NanH2 cleaved and foraged significantly more Neu5,9Ac2 than strains encoding only NanH3.
30723162	8	26	from	strains	1284:1290	arg1	present					1247:1253	present	1247:1253	present	1247:1253	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	10	27	theme	78	1724:1725	arg1	%					1726:1726	%	1726:1726	%	1726:1726	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	9	28	from	sialidases	1583:1592	arg1	specimens					1611:1619	human vaginal specimens	1597:1619	human vaginal specimens of women with BV	1597:1636	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	5	29	theme	recombinant	827:837	arg1	NanH1					839:843	recombinant NanH1	827:843	recombinant NanH1	827:843	In contrast, recombinant NanH1 had limited activity against synthetic and mucosal substrates under the conditions tested.
30723162	7	30	theme	vaginalis	1056:1064	arg1	strains					1066:1072	G. vaginalis strains	1053:1072	G. vaginalis strains encoding NanH2	1053:1087	Similarly, G. vaginalis strains encoding NanH2 cleaved and foraged significantly more Neu5,9Ac2 than strains encoding only NanH3.
30723162	0	31	dep	bacterium	114:122	arg1	vaginalis					136:144	Gardnerella vaginalis	124:144	the vaginal bacterium Gardnerella vaginalis	102:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	3	32	theme	BLAST	530:534	arg1	searches					536:543	BLAST searches	530:543	BLAST searches	530:543	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	2	33	theme	strains	360:366	arg1	subset					337:342	a subset	335:342	a subset of G. vaginalis strains	335:366	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	10	34	theme	81	1704:1705	arg1	%					1706:1706	%	1706:1706	%	1706:1706	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	4	35	theme	sialic	705:710	arg1	acids					712:716	sialic acids	705:716	sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans	705:772	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	9	36	theme	described	1544:1552	arg1	breadth					1564:1570	the previously described substrate breadth	1529:1570	the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV	1529:1636	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	4	37	link	O-linked	752:759	arg1	sialoglycans					761:772	O-linked sialoglycans	752:772	O-linked sialoglycans	752:772	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	2	38	theme	BV	313:314	arg1	activity					277:284	Sialidase activity	267:284	Sialidase activity	267:284	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	2	38	theme	BV	313:314	arg1	feature					302:308	a diagnostic feature	289:308	a diagnostic feature of BV	289:314	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	6	39	theme	Recombinant	936:946	arg1	NanH2					948:952	Recombinant NanH2	936:952	Recombinant NanH2	936:952	Recombinant NanH2 was much more effective than NanH3 in cleaving sialic acids bearing a 9-O-acetyl ester.
30723162	8	40	attach	present	1247:1253	arg2	both					1237:1240	both	1237:1240	both	1237:1240	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	40	attach	present	1247:1253	arg1	strains					1284:1290	all 15 sialidase-positive strains	1258:1290	all 15 sialidase-positive strains	1258:1290	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	40	attach	present	1247:1253	arg2	nanH3					1227:1231	nanH3	1227:1231	nanH3	1227:1231	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	40	attach	present	1247:1253	arg2	nanH2					1220:1224	nanH2	1220:1224	nanH2	1220:1224	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	9	41	from	sources	1440:1446	arg1	vaginalis					1476:1484	G. vaginalis	1473:1484	G. vaginalis	1473:1484	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	0	42	dep	enzymes	56:62	arg1	characterization					19:34	characterization	19:34	characterization	19:34	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	42	dep	enzymes	56:62	arg1	Identification					0:13	Identification	0:13	Identification	0:13	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	42	dep	enzymes	56:62	arg1	enzymes					56:62	enzymes	56:62	enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis	56:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	10	43	theme	nanH3	1665:1669	arg1	PCRs					1648:1651	PCRs	1648:1651	PCRs of nanH2 or nanH3 from human vaginal specimens	1648:1698	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	8	44	theme	sialidase-positive	1265:1282	arg1	strains					1284:1290	all 15 sialidase-positive strains	1258:1290	all 15 sialidase-positive strains	1258:1290	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	9	45	theme	primary	1432:1438	arg1	NanH3					1418:1422	NanH3	1418:1422	NanH3	1418:1422	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	9	45	theme	primary	1432:1438	arg1	NanH2					1408:1412	NanH2	1408:1412	NanH2	1408:1412	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	9	45	theme	primary	1432:1438	arg1	sources					1440:1446	the primary sources	1428:1446	the primary sources of sialidase activity in G. vaginalis	1428:1484	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	9	46	theme	substrate	1554:1562	arg1	breadth					1564:1570	the previously described substrate breadth	1529:1570	the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV	1529:1636	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	3	47	theme	sialidase	430:438	arg1	activity					440:447	sialidase activity	430:447	sialidase activity	430:447	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	0	48	theme	NanH2	39:43	arg1	characterization					19:34	characterization	19:34	characterization	19:34	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	48	theme	NanH2	39:43	arg1	Identification					0:13	Identification	0:13	Identification	0:13	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	48	theme	NanH2	39:43	arg1	enzymes					56:62	enzymes	56:62	enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis	56:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	3	49	theme	additional	559:568	arg1	NanH3					605:609	NanH3	605:609	NanH3	605:609	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	3	49	theme	additional	559:568	arg1	NanH2					595:599	NanH2	595:599	NanH2	595:599	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	3	49	theme	additional	559:568	arg1	sialidases					583:592	two additional G. vaginalis sialidases	555:592	two additional G. vaginalis sialidases	555:592	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	4	50	link	α2-6-linked	733:743	arg1	N-					745:746	α2-3- and α2-6-linked N-	723:746	α2-3- and α2-6-linked N-	723:746	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	3	51	theme	genetic	382:388	arg1	basis					390:394	its genetic basis	378:394	its genetic basis	378:394	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	4	52	theme	relevant	785:792	arg1	substrates					802:811	relevant mucosal substrates	785:811	relevant mucosal substrates	785:811	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	8	53	theme	sialidase-negative	1315:1332	arg1	isolates					1334:1341	all 19 sialidase-negative isolates	1308:1341	all 19 sialidase-negative isolates	1308:1341	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	53	theme	sialidase-negative	1315:1332	arg1	strains					1357:1363	16 strains	1354:1363	16 strains that were nanH1-positive	1354:1388	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	5	54	theme	synthetic	874:882	arg1	substrates					896:905	synthetic and mucosal substrates	874:905	synthetic and mucosal substrates	874:905	In contrast, recombinant NanH1 had limited activity against synthetic and mucosal substrates under the conditions tested.
30723162	0	55	theme	NanH3	49:53	arg1	characterization					19:34	characterization	19:34	characterization	19:34	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	55	theme	NanH3	49:53	arg1	Identification					0:13	Identification	0:13	Identification	0:13	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	55	theme	NanH3	49:53	arg1	enzymes					56:62	enzymes	56:62	enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis	56:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	9	56	theme	activity	1461:1468	arg1	NanH3					1418:1422	NanH3	1418:1422	NanH3	1418:1422	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	9	56	theme	activity	1461:1468	arg1	NanH2					1408:1412	NanH2	1408:1412	NanH2	1408:1412	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	9	56	theme	activity	1461:1468	arg1	sources					1440:1446	the primary sources	1428:1446	the primary sources of sialidase activity in G. vaginalis	1428:1484	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	10	57	theme	%	1726:1726	arg1	specificity					1728:1738	78% specificity	1724:1738	78% specificity	1724:1738	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	9	58	theme	sialidase	1451:1459	arg1	activity					1461:1468	sialidase activity	1451:1468	sialidase activity	1451:1468	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	10	59	from	specimens	1690:1698	arg1	nanH3					1665:1669	nanH3	1665:1669	nanH3	1665:1669	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	10	59	from	specimens	1690:1698	arg1	nanH2					1656:1660	nanH2	1656:1660	nanH2	1656:1660	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	10	59	from	specimens	1690:1698	arg1	PCRs					1648:1651	PCRs	1648:1651	PCRs of nanH2 or nanH3 from human vaginal specimens	1648:1698	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	9	60	theme	human	1597:1601	arg1	specimens					1611:1619	human vaginal specimens	1597:1619	human vaginal specimens of women with BV	1597:1636	We conclude that NanH2 and NanH3 are the primary sources of sialidase activity in G. vaginalis and that these two enzymes can account for the previously described substrate breadth cleaved by sialidases in human vaginal specimens of women with BV.
30723162	2	61	theme	Sialidase	267:275	arg1	activity					277:284	Sialidase activity	267:284	Sialidase activity	267:284	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	2	61	theme	Sialidase	267:275	arg1	feature					302:308	a diagnostic feature	289:308	a diagnostic feature of BV	289:314	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	4	62	from	sialoglycans	761:772	arg1	acids					712:716	sialic acids	705:716	sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans	705:772	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	3	63	dep	nanH1	509:513	arg1	predicted					545:553	predicted	545:553	predicted two additional G. vaginalis sialidases, NanH2 and NanH3	545:609	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	10	64	theme	human	1676:1680	arg1	specimens					1690:1698	human vaginal specimens	1676:1698	human vaginal specimens	1676:1698	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	6	65	theme	sialic	1001:1006	arg1	acids					1008:1012	sialic acids	1001:1012	sialic acids bearing a 9-O-acetyl ester	1001:1039	Recombinant NanH2 was much more effective than NanH3 in cleaving sialic acids bearing a 9-O-acetyl ester.
30723162	10	66	theme	vaginal	1682:1688	arg1	specimens					1690:1698	human vaginal specimens	1676:1698	human vaginal specimens	1676:1698	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	10	67	theme	Nugent	1815:1820	arg1	scoring					1822:1828	Nugent scoring	1815:1828	Nugent scoring	1815:1828	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	4	68	theme	α2-6-linked	733:743	arg1	N-					745:746	α2-3- and α2-6-linked N-	723:746	α2-3- and α2-6-linked N-	723:746	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	1	69	from	vaginosis	194:202	arg1	abundant					172:179	abundant	172:179	abundant	172:179	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
30723162	5	70	theme	limited	849:855	arg1	activity					857:864	limited activity	849:864	limited activity against synthetic and mucosal substrates	849:905	In contrast, recombinant NanH1 had limited activity against synthetic and mucosal substrates under the conditions tested.
30723162	4	71	theme	broad	679:683	arg1	abilities					685:693	broad abilities	679:693	broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans	679:772	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	0	72	theme	responsible	64:74	arg1	characterization					19:34	characterization	19:34	characterization	19:34	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	72	theme	responsible	64:74	arg1	enzymes					56:62	enzymes	56:62	enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis	56:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	72	theme	responsible	64:74	arg1	Identification					0:13	Identification	0:13	Identification	0:13	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	0	73	from	activity	90:97	arg1	bacterium					114:122	the vaginal bacterium Gardnerella vaginalis	102:144	the vaginal bacterium Gardnerella vaginalis	102:144	Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis.
30723162	4	74	theme	O-linked	752:759	arg1	sialoglycans					761:772	O-linked sialoglycans	752:772	O-linked sialoglycans	752:772	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	6	75	theme	9-O-acetyl	1024:1033	arg1	ester					1035:1039	a 9-O-acetyl ester	1022:1039	a 9-O-acetyl ester	1022:1039	Recombinant NanH2 was much more effective than NanH3 in cleaving sialic acids bearing a 9-O-acetyl ester.
30723162	2	76	theme	vaginalis	350:358	arg1	strains					360:366	G. vaginalis strains	347:366	G. vaginalis strains	347:366	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	8	77	theme	isolates	1210:1217	arg1	collection					1180:1189	a collection	1178:1189	a collection of 34 G. vaginalis isolates	1178:1217	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	8	78	theme	vaginalis	1200:1208	arg1	isolates					1210:1217	34 G. vaginalis isolates	1194:1217	34 G. vaginalis isolates	1194:1217	Among a collection of 34 G. vaginalis isolates, nanH2, nanH3, or both were present in all 15 sialidase-positive strains but absent from all 19 sialidase-negative isolates, including 16 strains that were nanH1-positive.
30723162	10	79	from	PCRs	1648:1651	arg1	specimens					1690:1698	human vaginal specimens	1676:1698	human vaginal specimens	1676:1698	Finally, PCRs of nanH2 or nanH3 from human vaginal specimens had 81% sensitivity and 78% specificity in distinguishing between Lactobacillus dominance and BV, as determined by Nugent scoring.
30723162	3	80	theme	vaginalis	573:581	arg1	NanH3					605:609	NanH3	605:609	NanH3	605:609	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	3	80	theme	vaginalis	573:581	arg1	NanH2					595:599	NanH2	595:599	NanH2	595:599	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	3	80	theme	vaginalis	573:581	arg1	sialidases					583:592	two additional G. vaginalis sialidases	555:592	two additional G. vaginalis sialidases	555:592	Although its genetic basis has not been formally identified, sialidase activity is presumed to derive from the sialidase A gene, named here nanH1 In this study, BLAST searches predicted two additional G. vaginalis sialidases, NanH2 and NanH3.
30723162	4	81	from	N-	745:746	arg1	acids					712:716	sialic acids	705:716	sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans	705:772	When expressed in Escherichia coli, NanH2 and NanH3 both displayed broad abilities to cleave sialic acids from α2-3- and α2-6-linked N- and O-linked sialoglycans, including relevant mucosal substrates.
30723162	2	82	theme	G.	347:348	arg1	strains					360:366	G. vaginalis strains	347:366	G. vaginalis strains	347:366	Sialidase activity is a diagnostic feature of BV and is produced by a subset of G. vaginalis strains.
30723162	1	83	theme	adverse	238:244	arg1	health					259:264	adverse reproductive health	238:264	adverse reproductive health	238:264	Gardnerella vaginalis is abundant in bacterial vaginosis (BV), a condition associated with adverse reproductive health.
31186110	6	0	theme	glycosylation	958:970	arg1	Heterogeneity					941:953	Heterogeneity	941:953	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris	941:1037	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	9	1	from	increase	1501:1508	arg1	half-life					1520:1528	plasma half-life	1513:1528	plasma half-life	1513:1528	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	7	2	theme	human	1202:1206	arg1	α2b					1232:1234	human type N-glycosylated IFN α2b	1202:1234	human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS)	1202:1304	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	2	3	theme	clinical	292:299	arg1	outcome					301:307	The clinical outcome	288:307	The clinical outcome of the approved recombinant human IFN α2b drugs in the market	288:369	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	8	4	theme	HEV	1410:1412	arg1	replication					1387:1397	the viral replication	1377:1397	the viral replication of HCV and HEV	1377:1412	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	7	5	theme	Recombinant	1163:1173	arg1	strain					1185:1190	Recombinant SuperMan5 strain	1163:1190	Recombinant SuperMan5 strain	1163:1190	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	3	6	theme	glycan	537:542	arg1	moieties					544:551	glycan moieties	537:551	glycan moieties	537:551	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	6	theme	glycan	537:542	arg1	cost					603:606	high production cost	587:606	high production cost	587:606	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	6	theme	glycan	537:542	arg1	quality					575:581	inconsistent product quality	554:581	inconsistent product quality	554:581	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	1	7	theme	IFN	182:184	arg1	α2b					186:188	IFN α2b	182:188	IFN α2b	182:188	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	7	theme	IFN	182:184	arg1	2b					178:179	Human interferon alpha 2b	155:179	Human interferon alpha 2b (IFN α2b)	155:189	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	4	8	theme	expression	679:688	arg1	platform					690:697	a successful expression platform	666:697	a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property	666:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	2	9	theme	approved	316:323	arg1	drugs					351:355	the approved recombinant human IFN α2b drugs	312:355	the approved recombinant human IFN α2b drugs	312:355	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	5	10	theme	human	920:924	arg1	drugs					934:938	approved recombinant human IFN α2b drugs	899:938	approved recombinant human IFN α2b drugs	899:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	6	11	theme	Pichia	1023:1028	arg1	pastoris					1030:1037	Pichia pastoris	1023:1037	Pichia pastoris	1023:1037	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	0	12	theme	N-linked	119:126	arg1	approach					145:152	N-linked glycoengineering approach	119:152	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	3	13	theme	product	567:573	arg1	moieties					544:551	glycan moieties	537:551	glycan moieties	537:551	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	13	theme	product	567:573	arg1	quality					575:581	inconsistent product quality	554:581	inconsistent product quality	554:581	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	0	14	theme	interferon	25:34	arg1	2b					42:43	Novel glycosylated human interferon alpha 2b	0:43	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	9	15	theme	IFN	1547:1549	arg1	α2b					1551:1553	glycosylated IFN α2b	1534:1553	glycosylated IFN α2b	1534:1553	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	4	16	theme	α2b	722:724	arg1	production					726:735	enhanced human IFN α2b production	703:735	enhanced human IFN α2b production with improved pharmacokinetic property	703:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	3	17	theme	production	592:601	arg1	cost					603:606	high production cost	587:606	high production cost	587:606	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	17	theme	production	592:601	arg1	moieties					544:551	glycan moieties	537:551	glycan moieties	537:551	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	6	18	theme	hypermannosylation	976:993	arg1	Heterogeneity					941:953	Heterogeneity	941:953	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris	941:1037	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	9	19	theme	standard	1567:1574	arg1	α2b					1580:1582	standard IFN α2b	1567:1582	standard IFN α2b produced by E. coli	1567:1602	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	2	20	from	outcome	301:307	arg1	market					364:369	the market	360:369	the market	360:369	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	9	21	gly	glycosylated	1534:1545	arg1	α2b					1551:1553	glycosylated IFN α2b	1534:1553	glycosylated IFN α2b	1534:1553	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	8	22	theme	HCV	1402:1404	arg1	replication					1387:1397	the viral replication	1377:1397	the viral replication of HCV and HEV	1377:1412	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	0	23	theme	glycoengineered	58:72	arg1	pastoris					81:88	glycoengineered Pichia pastoris	58:88	glycoengineered Pichia pastoris	58:88	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	7	24	theme	greater	1241:1247	arg1	homogeneity					1249:1259	greater homogeneity	1241:1259	greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS)	1241:1304	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	5	25	theme	α2b	930:932	arg1	drugs					934:938	approved recombinant human IFN α2b drugs	899:938	approved recombinant human IFN α2b drugs	899:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	6	26	theme	glycoengineered	1069:1083	arg1	strain					1085:1090	glycoengineered strain	1069:1090	glycoengineered strain (SuperMan5)	1069:1102	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	6	26	theme	glycoengineered	1069:1083	arg1	SuperMan5					1093:1101	SuperMan5	1093:1101	SuperMan5	1093:1101	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	4	27	theme	human	712:716	arg1	production					726:735	enhanced human IFN α2b production	703:735	enhanced human IFN α2b production with improved pharmacokinetic property	703:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	8	28	dep	active	1358:1363	arg1	inhibiting					1366:1375	inhibiting	1366:1375	inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively	1366:1441	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	28	dep	active	1358:1363	arg1	α2b					1337:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	28	dep	active	1358:1363	arg1	active					1358:1363	active	1358:1363	active	1358:1363	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	7	29	theme	glycan	1275:1280	arg1	analysis					1282:1289	glycan analysis	1275:1289	glycan analysis (MALDI-TOF/MS)	1275:1304	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	7	29	theme	glycan	1275:1280	arg1	MALDI-TOF/MS					1292:1303	MALDI-TOF/MS	1292:1303	MALDI-TOF/MS	1292:1303	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	0	30	theme	Pichia	74:79	arg1	pastoris					81:88	glycoengineered Pichia pastoris	58:88	glycoengineered Pichia pastoris	58:88	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	4	31	theme	pharmacokinetic	751:765	arg1	property					767:774	improved pharmacokinetic property	742:774	improved pharmacokinetic property	742:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	2	32	theme	short	384:388	arg1	half-life					397:405	short plasma half-life	384:405	short plasma half-life	384:405	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	5	33	theme	potential	842:850	arg1	site					868:871	potential N-glycosylation site	842:871	potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs	842:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	6	34	theme	IFN	1128:1130	arg1	α2b					1132:1134	glycosylated IFN α2b	1115:1134	glycosylated IFN α2b with human type N-glycans	1115:1160	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	2	35	theme	side	434:437	arg1	effects					439:445	other side effects	428:445	other side effects	428:445	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	3	36	theme	α2b	458:460	arg1	expression					462:471	Human IFN α2b expression	448:471	Human IFN α2b expression in mammalian cell lines	448:495	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	0	37	theme	human	19:23	arg1	2b					42:43	Novel glycosylated human interferon alpha 2b	0:43	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	6	38	with	α2b	1132:1134	arg1	N-glycans					1152:1160	human type N-glycans	1141:1160	human type N-glycans	1141:1160	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	1	39	theme	Human	155:159	arg1	α2b					186:188	IFN α2b	182:188	IFN α2b	182:188	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	39	theme	Human	155:159	arg1	interferon					203:212	a type I interferon	194:212	a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities	194:285	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	39	theme	Human	155:159	arg1	2b					178:179	Human interferon alpha 2b	155:179	Human interferon alpha 2b (IFN α2b)	155:189	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	3	40	theme	Human	448:452	arg1	expression					462:471	Human IFN α2b expression	448:471	Human IFN α2b expression in mammalian cell lines	448:495	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	2	41	theme	rapid	408:412	arg1	clearance					414:422	rapid clearance	408:422	rapid clearance	408:422	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	0	42	theme	alpha	36:40	arg1	2b					42:43	Novel glycosylated human interferon alpha 2b	0:43	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	0	43	gly	glycosylated	6:17	arg1	2b					42:43	Novel glycosylated human interferon alpha 2b	0:43	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	3	44	theme	cell	486:489	arg1	lines					491:495	mammalian cell lines	476:495	mammalian cell lines	476:495	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	7	45	theme	N-glycosylated	1213:1226	arg1	α2b					1232:1234	human type N-glycosylated IFN α2b	1202:1234	human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS)	1202:1304	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	3	46	from	expression	462:471	arg1	lines					491:495	mammalian cell lines	476:495	mammalian cell lines	476:495	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	2	47	theme	IFN	343:345	arg1	drugs					351:355	the approved recombinant human IFN α2b drugs	312:355	the approved recombinant human IFN α2b drugs	312:355	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	1	48	theme	interferon	161:170	arg1	α2b					186:188	IFN α2b	182:188	IFN α2b	182:188	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	48	theme	interferon	161:170	arg1	interferon					203:212	a type I interferon	194:212	a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities	194:285	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	48	theme	interferon	161:170	arg1	2b					178:179	Human interferon alpha 2b	155:179	Human interferon alpha 2b (IFN α2b)	155:189	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	4	49	theme	Potential	609:617	arg1	scope					619:623	Potential scope	609:623	Potential scope	609:623	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	3	50	theme	significant	508:518	arg1	heterogeneity					520:532	significant heterogeneity	508:532	significant heterogeneity in glycan moieties, inconsistent product quality and high production cost	508:606	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	5	51	theme	approved	899:906	arg1	drugs					934:938	approved recombinant human IFN α2b drugs	899:938	approved recombinant human IFN α2b drugs	899:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	1	52	theme	antiviral	225:233	arg1	activities					276:285	antiviral, anti-proliferative and immunomodulatory activities	225:285	antiviral, anti-proliferative and immunomodulatory activities	225:285	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	5	53	theme	IFN	829:831	arg1	α2b					833:835	IFN α2b	829:835	IFN α2b	829:835	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	4	54	with	production	726:735	arg1	property					767:774	improved pharmacokinetic property	742:774	improved pharmacokinetic property	742:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	1	55	theme	anti-proliferative	236:253	arg1	activities					276:285	antiviral, anti-proliferative and immunomodulatory activities	225:285	antiviral, anti-proliferative and immunomodulatory activities	225:285	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	9	56	theme	plasma	1513:1518	arg1	half-life					1520:1528	plasma half-life	1513:1528	plasma half-life	1513:1528	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	6	57	theme	type	1147:1150	arg1	N-glycans					1152:1160	human type N-glycans	1141:1160	human type N-glycans	1141:1160	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	7	58	theme	SuperMan5	1175:1183	arg1	strain					1185:1190	Recombinant SuperMan5 strain	1163:1190	Recombinant SuperMan5 strain	1163:1190	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	0	59	dep	2b	42:43	arg1	approach					145:152	N-linked glycoengineering approach	119:152	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	1	60	theme	immunomodulatory	259:274	arg1	activities					276:285	antiviral, anti-proliferative and immunomodulatory activities	225:285	antiviral, anti-proliferative and immunomodulatory activities	225:285	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	5	61	theme	drugs	934:938	arg1	drawbacks					886:894	the drawbacks	882:894	the drawbacks of approved recombinant human IFN α2b drugs	882:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	2	62	theme	drugs	351:355	arg1	outcome					301:307	The clinical outcome	288:307	The clinical outcome of the approved recombinant human IFN α2b drugs in the market	288:369	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	3	63	from	heterogeneity	520:532	arg1	moieties					544:551	glycan moieties	537:551	glycan moieties	537:551	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	63	from	heterogeneity	520:532	arg1	cost					603:606	high production cost	587:606	high production cost	587:606	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	63	from	heterogeneity	520:532	arg1	quality					575:581	inconsistent product quality	554:581	inconsistent product quality	554:581	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	9	64	theme	fold	1496:1499	arg1	increase					1501:1508	1.3 fold increase	1492:1508	1.3 fold increase in plasma half-life for glycosylated IFN α2b	1492:1553	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	7	65	with	α2b	1232:1234	arg1	homogeneity					1249:1259	greater homogeneity	1241:1259	greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS)	1241:1304	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	8	66	theme	purified	1311:1318	arg1	inhibiting					1366:1375	inhibiting	1366:1375	inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively	1366:1441	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	66	theme	purified	1311:1318	arg1	α2b					1337:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	66	theme	purified	1311:1318	arg1	active					1358:1363	active	1358:1363	active	1358:1363	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	2	67	theme	recombinant	325:335	arg1	drugs					351:355	the approved recombinant human IFN α2b drugs	312:355	the approved recombinant human IFN α2b drugs	312:355	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	5	68	theme	recombinant	908:918	arg1	drugs					934:938	approved recombinant human IFN α2b drugs	899:938	approved recombinant human IFN α2b drugs	899:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	6	69	theme	pastoris	1030:1037	arg1	strains					1012:1018	the wild-type strains	998:1018	the wild-type strains of Pichia pastoris	998:1037	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	4	70	theme	successful	668:677	arg1	platform					690:697	a successful expression platform	666:697	a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property	666:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	0	71	theme	glycoengineering	128:143	arg1	approach					145:152	N-linked glycoengineering approach	119:152	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	3	72	theme	inconsistent	554:565	arg1	moieties					544:551	glycan moieties	537:551	glycan moieties	537:551	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	72	theme	inconsistent	554:565	arg1	quality					575:581	inconsistent product quality	554:581	inconsistent product quality	554:581	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	8	73	gly	glycosylated	1320:1331	arg1	inhibiting					1366:1375	inhibiting	1366:1375	inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively	1366:1441	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	73	gly	glycosylated	1320:1331	arg1	α2b					1337:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	73	gly	glycosylated	1320:1331	arg1	active					1358:1363	active	1358:1363	active	1358:1363	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	74	theme	IFN	1333:1335	arg1	inhibiting					1366:1375	inhibiting	1366:1375	inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively	1366:1441	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	74	theme	IFN	1333:1335	arg1	α2b					1337:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	74	theme	IFN	1333:1335	arg1	active					1358:1363	active	1358:1363	active	1358:1363	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	1	75	theme	type	196:199	arg1	interferon					203:212	a type I interferon	194:212	a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities	194:285	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	75	theme	type	196:199	arg1	2b					178:179	Human interferon alpha 2b	155:179	Human interferon alpha 2b (IFN α2b)	155:189	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	6	76	theme	wild-type	1002:1010	arg1	strains					1012:1018	the wild-type strains	998:1018	the wild-type strains of Pichia pastoris	998:1037	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	3	77	theme	high	587:590	arg1	cost					603:606	high production cost	587:606	high production cost	587:606	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	3	77	theme	high	587:590	arg1	moieties					544:551	glycan moieties	537:551	glycan moieties	537:551	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	4	78	theme	IFN	718:720	arg1	production					726:735	enhanced human IFN α2b production	703:735	enhanced human IFN α2b production with improved pharmacokinetic property	703:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	8	79	theme	viral	1381:1385	arg1	replication					1387:1397	the viral replication	1377:1397	the viral replication of HCV and HEV	1377:1412	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	5	80	theme	Glycoengineering	777:792	arg1	strategy					794:801	Glycoengineering strategy	777:801	Glycoengineering strategy	777:801	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	9	81	theme	IFN	1576:1578	arg1	α2b					1580:1582	standard IFN α2b	1567:1582	standard IFN α2b produced by E. coli	1567:1602	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	5	82	theme	IFN	926:928	arg1	drugs					934:938	approved recombinant human IFN α2b drugs	899:938	approved recombinant human IFN α2b drugs	899:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	4	83	theme	platform	690:697	arg1	development					651:661	development	651:661	development	651:661	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	4	83	theme	platform	690:697	arg1	design					640:645	design	640:645	design	640:645	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	1	84	theme	alpha	172:176	arg1	α2b					186:188	IFN α2b	182:188	IFN α2b	182:188	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	84	theme	alpha	172:176	arg1	interferon					203:212	a type I interferon	194:212	a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities	194:285	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	1	84	theme	alpha	172:176	arg1	2b					178:179	Human interferon alpha 2b	155:179	Human interferon alpha 2b (IFN α2b)	155:189	Human interferon alpha 2b (IFN α2b) is a type I interferon exhibiting antiviral, anti-proliferative and immunomodulatory activities.
31186110	4	85	theme	enhanced	703:710	arg1	production					726:735	enhanced human IFN α2b production	703:735	enhanced human IFN α2b production with improved pharmacokinetic property	703:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	6	86	gly	Heterogeneity	941:953	arg1	hypermannosylation					976:993	hypermannosylation	976:993	hypermannosylation	976:993	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	6	86	gly	Heterogeneity	941:953	arg1	glycosylation					958:970	glycosylation	958:970	glycosylation	958:970	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	0	87	theme	biological	98:107	arg1	activity					109:116	its biological activity	94:116	its biological activity	94:116	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	0	88	theme	Novel	0:4	arg1	2b					42:43	Novel glycosylated human interferon alpha 2b	0:43	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	2	89	theme	human	337:341	arg1	drugs					351:355	the approved recombinant human IFN α2b drugs	312:355	the approved recombinant human IFN α2b drugs	312:355	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	6	90	theme	human	1141:1145	arg1	N-glycans					1152:1160	human type N-glycans	1141:1160	human type N-glycans	1141:1160	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	2	91	theme	plasma	390:395	arg1	half-life					397:405	short plasma half-life	384:405	short plasma half-life	384:405	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	0	92	theme	glycosylated	6:17	arg1	2b					42:43	Novel glycosylated human interferon alpha 2b	0:43	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	0	93	link	N-linked	119:126	arg1	approach					145:152	N-linked glycoengineering approach	119:152	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.	0:153	Novel glycosylated human interferon alpha 2b expressed in glycoengineered Pichia pastoris and its biological activity: N-linked glycoengineering approach.
31186110	8	94	theme	glycosylated	1320:1331	arg1	inhibiting					1366:1375	inhibiting	1366:1375	inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively	1366:1441	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	94	theme	glycosylated	1320:1331	arg1	α2b					1337:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b	1307:1339	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	8	94	theme	glycosylated	1320:1331	arg1	active					1358:1363	active	1358:1363	active	1358:1363	The purified glycosylated IFN α2b was biologically active, inhibiting the viral replication of HCV and HEV at 85% and 66%, respectively.
31186110	4	95	theme	improved	742:749	arg1	property					767:774	improved pharmacokinetic property	742:774	improved pharmacokinetic property	742:774	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	5	96	theme	N-glycosylation	852:866	arg1	site					868:871	potential N-glycosylation site	842:871	potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs	842:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	6	97	theme	glycosylated	1115:1126	arg1	α2b					1132:1134	glycosylated IFN α2b	1115:1134	glycosylated IFN α2b with human type N-glycans	1115:1160	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	2	98	theme	other	428:432	arg1	effects					439:445	other side effects	428:445	other side effects	428:445	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	6	99	gly	glycosylated	1115:1126	arg1	α2b					1132:1134	glycosylated IFN α2b	1115:1134	glycosylated IFN α2b with human type N-glycans	1115:1160	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
31186110	7	100	theme	IFN	1228:1230	arg1	α2b					1232:1234	human type N-glycosylated IFN α2b	1202:1234	human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS)	1202:1304	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	9	101	theme	glycosylated	1534:1545	arg1	α2b					1551:1553	glycosylated IFN α2b	1534:1553	glycosylated IFN α2b	1534:1553	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	9	102	theme	Wistar	1471:1476	arg1	rats					1478:1481	Wistar rats	1471:1481	Wistar rats	1471:1481	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	3	103	theme	IFN	454:456	arg1	expression					462:471	Human IFN α2b expression	448:471	Human IFN α2b expression in mammalian cell lines	448:495	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	7	104	theme	type	1208:1211	arg1	α2b					1232:1234	human type N-glycosylated IFN α2b	1202:1234	human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS)	1202:1304	Recombinant SuperMan5 strain expressed human type N-glycosylated IFN α2b with greater homogeneity elucidated by glycan analysis (MALDI-TOF/MS).
31186110	9	105	from	studies	1460:1466	arg1	rats					1478:1481	Wistar rats	1471:1481	Wistar rats	1471:1481	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	4	106	dep	design	640:645	arg1	the					636:638	the	636:638	the	636:638	Potential scope exists for the design and development of a successful expression platform for enhanced human IFN α2b production with improved pharmacokinetic property.
31186110	5	107	gly	N-glycosylation	852:866	arg2	site					868:871	potential N-glycosylation site	842:871	potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs	842:938	Glycoengineering strategy was employed to construct IFN α2b with potential N-glycosylation site to evade the drawbacks of approved recombinant human IFN α2b drugs.
31186110	2	108	theme	α2b	347:349	arg1	drugs					351:355	the approved recombinant human IFN α2b drugs	312:355	the approved recombinant human IFN α2b drugs	312:355	The clinical outcome of the approved recombinant human IFN α2b drugs in the market suffers from short plasma half-life, rapid clearance and other side effects.
31186110	3	109	theme	mammalian	476:484	arg1	lines					491:495	mammalian cell lines	476:495	mammalian cell lines	476:495	Human IFN α2b expression in mammalian cell lines results in significant heterogeneity in glycan moieties, inconsistent product quality and high production cost.
31186110	9	110	theme	Pharmacokinetic	1444:1458	arg1	studies					1460:1466	Pharmacokinetic studies	1444:1466	Pharmacokinetic studies in Wistar rats	1444:1481	Pharmacokinetic studies in Wistar rats revealed 1.3 fold increase in plasma half-life for glycosylated IFN α2b compared to standard IFN α2b produced by E. coli.
31186110	6	111	from	Heterogeneity	941:953	arg1	strains					1012:1018	the wild-type strains	998:1018	the wild-type strains of Pichia pastoris	998:1037	Heterogeneity of glycosylation and hypermannosylation in the wild-type strains of Pichia pastoris was circumvented by employing glycoengineered strain (SuperMan5) to produce glycosylated IFN α2b with human type N-glycans.
30622981	6	0	theme	glycoconjugate	1107:1120	arg1	vaccine					1122:1128	this glycoconjugate vaccine	1102:1128	this glycoconjugate vaccine	1102:1128	We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4.
30622981	3	1	theme	exoprotein	714:723	arg1	ExoA					728:731	ExoA	728:731	ExoA	728:731	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	1	theme	exoprotein	714:723	arg1	A					725:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A	659:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA)	659:732	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	4	2	theme	glycosylation	800:812	arg1	sequons					814:820	two glycosylation sequons	796:820	two glycosylation sequons	796:820	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	4	3	theme	low-virulence	905:917	arg1	strain					919:924	a low-virulence strain	903:924	a low-virulence strain of F. tularensis	903:941	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	5	4	theme	Fischer	1046:1052	arg1	model					1062:1066	a Fischer 344 rat model	1044:1066	a Fischer 344 rat model of tularemia	1044:1079	Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia.
30622981	1	5	theme	etiological	262:272	arg1	tularensis					246:255	Francisella tularensis	234:255	Francisella tularensis	234:255	There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia.
30622981	1	5	theme	etiological	262:272	arg1	agent					274:278	the etiological agent	258:278	the etiological agent of tularemia	258:291	There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia.
30622981	5	6	theme	glycosylated	983:994	arg1	vaccine					1006:1012	a more heavily glycosylated conjugate vaccine	968:1012	a more heavily glycosylated conjugate vaccine	968:1012	Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia.
30622981	4	7	theme	ExoA	771:774	arg1	glycoconjugate					776:789	an ExoA glycoconjugate	768:789	an ExoA glycoconjugate with two glycosylation sequons	768:820	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	4	7	theme	ExoA	771:774	arg1	capable					826:832	capable	826:832	capable	826:832	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	0	8	theme	Rat	119:121	arg1	Model					123:127	an Inhalational Rat Model	103:127	an Inhalational Rat Model of Tularemia	103:140	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	7	9	theme	subunit	1346:1352	arg1	vaccines					1354:1361	next-generation tularemia subunit vaccines	1320:1361	next-generation tularemia subunit vaccines	1320:1361	Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.
30622981	3	10	theme	coupling	523:530	arg1	PGCT					544:547	PGCT	544:547	PGCT	544:547	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	10	theme	coupling	523:530	arg1	technology					532:541	protein glycan coupling technology	508:541	protein glycan coupling technology (PGCT)	508:548	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	1	11	theme	efficacious	173:183	arg1	vaccine					185:191	an efficacious vaccine	170:191	an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia	170:291	There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia.
30622981	3	12	theme	efficacious	432:442	arg1	vaccine					452:458	a more efficacious subunit vaccine	425:458	a more efficacious subunit vaccine	425:458	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	0	13	theme	Inhalational	106:117	arg1	Model					123:127	an Inhalational Rat Model	103:127	an Inhalational Rat Model of Tularemia	103:140	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	4	14	gly	glycosylation	800:812	arg2	sequons					814:820	two glycosylation sequons	796:820	two glycosylation sequons	796:820	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	3	15	theme	technology	532:541	arg1	technique					495:503	a novel biosynthetic technique	474:503	a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation	474:595	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	16	theme	subunit	444:450	arg1	vaccine					452:458	a more efficacious subunit vaccine	425:458	a more efficacious subunit vaccine	425:458	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	0	17	theme	O-Antigen	3:11	arg1	Vaccine					28:34	An O-Antigen Glycoconjugate Vaccine	0:34	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology	0:84	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	0	17	theme	O-Antigen	3:11	arg1	Protective					89:98	Protective	89:98	Protective	89:98	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	2	18	dep	F.	326:327	arg1	tularensis					329:338	F. tularensis	326:338	F. tularensis	326:338	The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice.
30622981	2	19	theme	lethal	388:393	arg1	challenge					395:403	a parenteral lethal challenge	375:403	a parenteral lethal challenge in mice	375:411	The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice.
30622981	6	20	with	challenge	1198:1206	arg1	S4					1232:1233	S4	1232:1233	S4	1232:1233	We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4.
30622981	5	21	theme	tularemia	1071:1079	arg1	model					1062:1066	a Fischer 344 rat model	1044:1066	a Fischer 344 rat model of tularemia	1044:1079	Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia.
30622981	3	22	theme	bacterial	564:572	arg1	glycosylation					583:595	bacterial N-linked glycosylation	564:595	bacterial N-linked glycosylation	564:595	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	2	23	theme	parenteral	377:386	arg1	challenge					395:403	a parenteral lethal challenge	375:403	a parenteral lethal challenge in mice	375:411	The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice.
30622981	1	24	theme	tularemia	283:291	arg1	tularensis					246:255	Francisella tularensis	234:255	Francisella tularensis	234:255	There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia.
30622981	1	24	theme	tularemia	283:291	arg1	agent					274:278	the etiological agent	258:278	the etiological agent of tularemia	258:291	There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia.
30622981	5	25	theme	rat	1058:1060	arg1	model					1062:1066	a Fischer 344 rat model	1044:1066	a Fischer 344 rat model of tularemia	1044:1079	Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia.
30622981	7	26	theme	tularemia	1336:1344	arg1	vaccines					1354:1361	next-generation tularemia subunit vaccines	1320:1361	next-generation tularemia subunit vaccines	1320:1361	Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.
30622981	0	27	theme	Glycoconjugate	13:26	arg1	Vaccine					28:34	An O-Antigen Glycoconjugate Vaccine	0:34	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology	0:84	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	0	27	theme	Glycoconjugate	13:26	arg1	Protective					89:98	Protective	89:98	Protective	89:98	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	4	28	with	glycoconjugate	776:789	arg1	sequons					814:820	two glycosylation sequons	796:820	two glycosylation sequons	796:820	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	5	29	theme	conjugate	996:1004	arg1	vaccine					1006:1012	a more heavily glycosylated conjugate vaccine	968:1012	a more heavily glycosylated conjugate vaccine	968:1012	Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia.
30622981	0	30	from	Protective	89:98	arg1	Model					123:127	an Inhalational Rat Model	103:127	an Inhalational Rat Model of Tularemia	103:140	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	7	31	theme	vaccines	1354:1361	arg1	creation					1308:1315	the creation	1304:1315	the creation of next-generation tularemia subunit vaccines	1304:1361	Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.
30622981	3	32	dep	F.	624:625	arg1	tularensis					627:636	F. tularensis	624:636	F. tularensis O-antigen glycans	624:654	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	33	link	N-linked	574:581	arg1	glycosylation					583:595	bacterial N-linked glycosylation	564:595	bacterial N-linked glycosylation	564:595	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	5	34	from	efficacy	1032:1039	arg1	model					1062:1066	a Fischer 344 rat model	1044:1066	a Fischer 344 rat model of tularemia	1044:1079	Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia.
30622981	3	35	theme	immunogenic	663:673	arg1	ExoA					728:731	ExoA	728:731	ExoA	728:731	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	35	theme	immunogenic	663:673	arg1	A					725:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A	659:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA)	659:732	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	6	36	dep	F.	1213:1214	arg1	tularensis					1216:1225	F. tularensis	1213:1225	F. tularensis Schu S4	1213:1233	We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4.
30622981	0	37	theme	Tularemia	132:140	arg1	Model					123:127	an Inhalational Rat Model	103:127	an Inhalational Rat Model of Tularemia	103:140	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	3	38	used	used	469:472	arg2	we					461:462	we	461:462	we	461:462	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	7	39	theme	next-generation	1320:1334	arg1	vaccines					1354:1361	next-generation tularemia subunit vaccines	1320:1361	next-generation tularemia subunit vaccines	1320:1361	Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.
30622981	0	40	theme	Glycan	59:64	arg1	Technology					75:84	Protein Glycan Coupling Technology	51:84	Protein Glycan Coupling Technology	51:84	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	4	41	dep	F.	929:930	arg1	tularensis					932:941	F. tularensis	929:941	F. tularensis	929:941	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	3	42	theme	N-linked	574:581	arg1	glycosylation					583:595	bacterial N-linked glycosylation	564:595	bacterial N-linked glycosylation	564:595	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	43	theme	novel	476:480	arg1	technique					495:503	a novel biosynthetic technique	474:503	a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation	474:595	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	0	44	theme	Protein	51:57	arg1	Technology					75:84	Protein Glycan Coupling Technology	51:84	Protein Glycan Coupling Technology	51:84	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	3	45	theme	Pseudomonas	691:701	arg1	ExoA					728:731	ExoA	728:731	ExoA	728:731	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	45	theme	Pseudomonas	691:701	arg1	A					725:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A	659:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA)	659:732	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	4	46	theme	significant	847:857	arg1	protection					859:868	significant protection	847:868	significant protection to mice against a challenge with a low-virulence strain of F. tularensis	847:941	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	3	47	theme	biosynthetic	482:493	arg1	technique					495:503	a novel biosynthetic technique	474:503	a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation	474:595	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	48	theme	aeruginosa	703:712	arg1	ExoA					728:731	ExoA	728:731	ExoA	728:731	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	48	theme	aeruginosa	703:712	arg1	A					725:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A	659:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA)	659:732	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	2	49	from	challenge	395:403	arg1	mice					408:411	mice	408:411	mice	408:411	The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice.
30622981	2	50	theme	F.	326:327	arg1	protective					356:365	protective	356:365	protective	356:365	The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice.
30622981	2	50	theme	F.	326:327	arg1	LPS					318:320	LPS	318:320	LPS	318:320	The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice.
30622981	2	50	theme	F.	326:327	arg1	lipopolysaccharide					298:315	The lipopolysaccharide	294:315	The lipopolysaccharide (LPS) of F. tularensis	294:338	The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice.
30622981	4	51	theme	F.	929:930	arg1	strain					919:924	a low-virulence strain	903:924	a low-virulence strain of F. tularensis	903:941	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	3	52	theme	carrier	675:681	arg1	ExoA					728:731	ExoA	728:731	ExoA	728:731	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	52	theme	carrier	675:681	arg1	A					725:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A	659:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA)	659:732	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	53	theme	O-antigen	638:646	arg1	glycans					648:654	F. tularensis O-antigen glycans	624:654	F. tularensis O-antigen glycans	624:654	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	6	54	theme	challenge	1198:1206	arg1	disease					1153:1159	disease	1153:1159	disease	1153:1159	We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4.
30622981	6	54	theme	challenge	1198:1206	arg1	lethality					1169:1177	the lethality	1165:1177	the lethality of an inhalational challenge with F. tularensis Schu S4	1165:1233	We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4.
30622981	7	55	theme	biosynthetic	1278:1289	arg1	approach					1291:1298	this biosynthetic approach	1273:1298	this biosynthetic approach	1273:1298	Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.
30622981	7	56	theme	approach	1291:1298	arg1	potential					1260:1268	the potential	1256:1268	the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines	1256:1361	Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines.
30622981	5	57	gly	glycosylated	983:994	arg1	vaccine					1006:1012	a more heavily glycosylated conjugate vaccine	968:1012	a more heavily glycosylated conjugate vaccine	968:1012	Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia.
30622981	3	58	theme	protein	683:689	arg1	ExoA					728:731	ExoA	728:731	ExoA	728:731	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	58	theme	protein	683:689	arg1	A					725:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A	659:725	the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA)	659:732	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	6	59	theme	inhalational	1185:1196	arg1	challenge					1198:1206	an inhalational challenge	1182:1206	an inhalational challenge with F. tularensis Schu S4	1182:1233	We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4.
30622981	3	60	theme	protein	508:514	arg1	PGCT					544:547	PGCT	544:547	PGCT	544:547	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	60	theme	protein	508:514	arg1	technology					532:541	protein glycan coupling technology	508:541	protein glycan coupling technology (PGCT)	508:548	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	4	61	with	challenge	888:896	arg1	strain					919:924	a low-virulence strain	903:924	a low-virulence strain of F. tularensis	903:941	Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis.
30622981	1	62	theme	Francisella	234:244	arg1	tularensis					246:255	Francisella tularensis	234:255	Francisella tularensis	234:255	There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia.
30622981	1	62	theme	Francisella	234:244	arg1	agent					274:278	the etiological agent	258:278	the etiological agent of tularemia	258:291	There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia.
30622981	0	63	theme	Coupling	66:73	arg1	Technology					75:84	Protein Glycan Coupling Technology	51:84	Protein Glycan Coupling Technology	51:84	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	3	64	theme	F.	624:625	arg1	glycans					648:654	F. tularensis O-antigen glycans	624:654	F. tularensis O-antigen glycans	624:654	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	65	theme	glycan	516:521	arg1	PGCT					544:547	PGCT	544:547	PGCT	544:547	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	3	65	theme	glycan	516:521	arg1	technology					532:541	protein glycan coupling technology	508:541	protein glycan coupling technology (PGCT)	508:548	To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA).
30622981	0	66	from	Model	123:127	arg1	Protective					89:98	Protective	89:98	Protective	89:98	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30622981	0	66	from	Model	123:127	arg1	Vaccine					28:34	An O-Antigen Glycoconjugate Vaccine	0:34	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology	0:84	An O-Antigen Glycoconjugate Vaccine Produced Using Protein Glycan Coupling Technology Is Protective in an Inhalational Rat Model of Tularemia.
30577605	10	0	theme	potential	1487:1495	arg1	type					1463:1466	a specific type	1452:1466	a specific type of N-glycan	1452:1478	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	10	0	theme	potential	1487:1495	arg1	target					1497:1502	the potential target	1483:1502	the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression	1483:1568	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	1	1	theme	carcinoma	164:172	arg1	prognosis					136:144	The poor prognosis	127:144	The poor prognosis of hepatocellular carcinoma (HCC)	127:178	The poor prognosis of hepatocellular carcinoma (HCC) is resulted from tumor metastasis.
30577605	0	2	theme	N-glycan	15:22	arg1	Involvement					0:10	Involvement	0:10	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases	0:60	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases Targeted by Ling-Zhi-8 for Suppressing HCC413 Tumor Progression.
30577605	9	3	theme	LZ-8	1373:1376	arg1	suppression					1388:1398	LZ-8 triggered suppression	1373:1398	LZ-8 triggered suppression of tumor growth of HCC413	1373:1424	Moreover, pretreatment of KIF prevented LZ-8 triggered suppression of tumor growth of HCC413.
30577605	5	4	theme	phosphorylated	773:786	arg1	ERK					793:795	ERK	793:795	ERK involved in HCC progression	793:823	These led to the suppression of downstream signaling including phosphorylated JNK, ERK involved in HCC progression.
30577605	5	4	theme	phosphorylated	773:786	arg1	JNK					788:790	phosphorylated JNK	773:790	phosphorylated JNK	773:790	These led to the suppression of downstream signaling including phosphorylated JNK, ERK involved in HCC progression.
30577605	2	5	theme	progression	353:363	arg1	prevention					335:344	prevention	335:344	prevention of HCC progression	335:363	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	4	6	theme	Ganoderma	580:588	arg1	lucidium					590:597	Ganoderma lucidium	580:597	Ganoderma lucidium	580:597	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	0	7	theme	HCC413	101:106	arg1	Progression					114:124	HCC413 Tumor Progression	101:124	HCC413 Tumor Progression	101:124	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases Targeted by Ling-Zhi-8 for Suppressing HCC413 Tumor Progression.
30577605	0	8	from	Involvement	0:10	arg1	Kinases					54:60	Multiple Receptor Tyrosine Kinases	27:60	Multiple Receptor Tyrosine Kinases	27:60	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases Targeted by Ling-Zhi-8 for Suppressing HCC413 Tumor Progression.
30577605	7	9	theme	N-linked	953:960	arg1	motif					969:973	the N-linked glycan motif	949:973	the N-linked glycan motif of RTKs that is required for their maturation and function	949:1032	LZ-8 may bind on the N-linked glycan motif of RTKs that is required for their maturation and function.
30577605	10	10	theme	multiple	1524:1531	arg1	RTKs					1533:1536	multiple RTKs	1524:1536	multiple RTKs	1524:1536	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	8	11	theme	N-glycosylation	1130:1144	arg1	mannosidase					1117:1127	the mannosidase	1113:1127	the mannosidase (N-glycosylation processing enzyme)	1113:1163	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	11	theme	N-glycosylation	1130:1144	arg1	enzyme					1157:1162	N-glycosylation processing enzyme	1130:1162	N-glycosylation processing enzyme	1130:1162	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	6	12	theme	simultaneous	896:907	arg1	binding					909:915	its simultaneous binding	892:915	its simultaneous binding to these RTKs	892:929	The capability of LZ-8 in targeting multiple RTKs was ascribed to its simultaneous binding to these RTKs.
30577605	8	13	theme	cell	1298:1301	arg1	migration					1303:1311	cell migration	1298:1311	cell migration	1298:1311	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	4	14	theme	various	696:702	arg1	RTKs					704:707	various RTKs	696:707	various RTKs	696:707	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	7	15	link	N-linked	953:960	arg1	motif					969:973	the N-linked glycan motif	949:973	the N-linked glycan motif of RTKs that is required for their maturation and function	949:1032	LZ-8 may bind on the N-linked glycan motif of RTKs that is required for their maturation and function.
30577605	4	16	from	lucidium	590:597	arg1	peptide					567:573	a medicinal peptide	555:573	a medicinal peptide from Ganoderma lucidium	555:597	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	4	16	from	lucidium	590:597	arg1	Ling-Zhi-8					536:545	Ling-Zhi-8	536:545	Ling-Zhi-8 (LZ-8)	536:552	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	3	17	theme	RTKs	497:500	arg1	signaling					502:510	compensatory RTKs signaling	484:510	compensatory RTKs signaling	484:510	However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling.
30577605	9	18	theme	tumor	1403:1407	arg1	growth					1409:1414	tumor growth	1403:1414	tumor growth of HCC413	1403:1424	Moreover, pretreatment of KIF prevented LZ-8 triggered suppression of tumor growth of HCC413.
30577605	0	19	theme	Tumor	108:112	arg1	Progression					114:124	HCC413 Tumor Progression	101:124	HCC413 Tumor Progression	101:124	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases Targeted by Ling-Zhi-8 for Suppressing HCC413 Tumor Progression.
30577605	8	20	dep	trimming	1073:1080	arg1	PNGase					1089:1094	enzyme PNGase	1082:1094	enzyme PNGase	1082:1094	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	20	dep	trimming	1073:1080	arg1	swainsonine					1188:1198	swainsonine	1188:1198	swainsonine (SWN)	1188:1204	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	20	dep	trimming	1073:1080	arg1	kifunensine					1166:1176	kifunensine	1166:1176	kifunensine (KIF)	1166:1182	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	20	dep	trimming	1073:1080	arg1	inhibitors					1099:1108	inhibitors	1099:1108	inhibitors of the mannosidase (N-glycosylation processing enzyme)	1099:1163	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	9	21	theme	growth	1409:1414	arg1	suppression					1388:1398	LZ-8 triggered suppression	1373:1398	LZ-8 triggered suppression of tumor growth of HCC413	1373:1424	Moreover, pretreatment of KIF prevented LZ-8 triggered suppression of tumor growth of HCC413.
30577605	10	22	theme	HCC	1554:1556	arg1	progression					1558:1568	HCC progression	1554:1568	HCC progression	1554:1568	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	8	23	theme	mannosidase	1117:1127	arg1	PNGase					1089:1094	enzyme PNGase	1082:1094	enzyme PNGase	1082:1094	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	23	theme	mannosidase	1117:1127	arg1	swainsonine					1188:1198	swainsonine	1188:1198	swainsonine (SWN)	1188:1204	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	23	theme	mannosidase	1117:1127	arg1	kifunensine					1166:1176	kifunensine	1166:1176	kifunensine (KIF)	1166:1182	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	23	theme	mannosidase	1117:1127	arg1	inhibitors					1099:1108	inhibitors	1099:1108	inhibitors of the mannosidase (N-glycosylation processing enzyme)	1099:1163	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	3	24	theme	kinase-based	419:430	arg1	inhibitors					432:441	conventional kinase-based inhibitors	406:441	conventional kinase-based inhibitors	406:441	However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling.
30577605	5	25	theme	HCC	809:811	arg1	progression					813:823	HCC progression	809:823	HCC progression	809:823	These led to the suppression of downstream signaling including phosphorylated JNK, ERK involved in HCC progression.
30577605	4	26	theme	medicinal	557:565	arg1	peptide					567:573	a medicinal peptide	555:573	a medicinal peptide from Ganoderma lucidium	555:597	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	4	26	theme	medicinal	557:565	arg1	Ling-Zhi-8					536:545	Ling-Zhi-8	536:545	Ling-Zhi-8 (LZ-8)	536:552	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	2	27	theme	therapeutic	311:321	arg1	pathways					225:232	Signaling pathways	215:232	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs)	215:290	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	2	27	theme	therapeutic	311:321	arg1	targets					323:329	the promising therapeutic targets	297:329	the promising therapeutic targets for prevention of HCC progression	297:363	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	8	28	theme	LZ-8	1217:1220	arg1	binding					1222:1228	LZ-8 binding	1217:1228	LZ-8 binding	1217:1228	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	9	29	theme	HCC413	1419:1424	arg1	growth					1409:1414	tumor growth	1403:1414	tumor growth of HCC413	1403:1424	Moreover, pretreatment of KIF prevented LZ-8 triggered suppression of tumor growth of HCC413.
30577605	3	30	theme	RTK-based	375:383	arg1	therapy					392:398	RTK-based target therapy	375:398	RTK-based target therapy using conventional kinase-based inhibitors	375:441	However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling.
30577605	2	31	theme	promising	301:309	arg1	pathways					225:232	Signaling pathways	215:232	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs)	215:290	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	2	31	theme	promising	301:309	arg1	targets					323:329	the promising therapeutic targets	297:329	the promising therapeutic targets for prevention of HCC progression	297:363	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	3	32	theme	compensatory	484:495	arg1	signaling					502:510	compensatory RTKs signaling	484:510	compensatory RTKs signaling	484:510	However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling.
30577605	3	33	theme	target	385:390	arg1	therapy					392:398	RTK-based target therapy	375:398	RTK-based target therapy using conventional kinase-based inhibitors	375:441	However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling.
30577605	10	34	theme	specific	1454:1461	arg1	type					1463:1466	a specific type	1452:1466	a specific type of N-glycan	1452:1478	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	10	34	theme	specific	1454:1461	arg1	target					1497:1502	the potential target	1483:1502	the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression	1483:1568	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	1	35	theme	tumor	197:201	arg1	metastasis					203:212	tumor metastasis	197:212	tumor metastasis	197:212	The poor prognosis of hepatocellular carcinoma (HCC) is resulted from tumor metastasis.
30577605	0	36	theme	Receptor	36:43	arg1	Kinases					54:60	Multiple Receptor Tyrosine Kinases	27:60	Multiple Receptor Tyrosine Kinases	27:60	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases Targeted by Ling-Zhi-8 for Suppressing HCC413 Tumor Progression.
30577605	8	37	theme	aforementioned	1237:1250	arg1	RTKs					1252:1255	the aforementioned RTKs	1233:1255	the aforementioned RTKs	1233:1255	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	38	theme	trimming	1073:1080	arg1	pretreatment					1044:1055	pretreatment	1044:1055	pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN),	1044:1205	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	6	39	theme	multiple	862:869	arg1	RTKs					871:874	multiple RTKs	862:874	multiple RTKs	862:874	The capability of LZ-8 in targeting multiple RTKs was ascribed to its simultaneous binding to these RTKs.
30577605	3	40	theme	due	477:479	arg1	resistances					465:475	resistances	465:475	resistances due to compensatory RTKs signaling	465:510	However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling.
30577605	0	41	theme	Multiple	27:34	arg1	Kinases					54:60	Multiple Receptor Tyrosine Kinases	27:60	Multiple Receptor Tyrosine Kinases	27:60	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases Targeted by Ling-Zhi-8 for Suppressing HCC413 Tumor Progression.
30577605	8	42	theme	N-glycan	1064:1071	arg1	trimming					1073:1080	the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN),	1060:1205	the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN),	1060:1205	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	9	43	theme	KIF	1359:1361	arg1	pretreatment					1343:1354	pretreatment	1343:1354	pretreatment of KIF	1343:1361	Moreover, pretreatment of KIF prevented LZ-8 triggered suppression of tumor growth of HCC413.
30577605	4	44	theme	HCC413	647:652	arg1	migration					634:642	cell migration	629:642	cell migration of HCC413	629:652	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	3	45	theme	conventional	406:417	arg1	inhibitors					432:441	conventional kinase-based inhibitors	406:441	conventional kinase-based inhibitors	406:441	However, RTK-based target therapy using conventional kinase-based inhibitors was often hampered by resistances due to compensatory RTKs signaling.
30577605	8	46	theme	processing	1146:1155	arg1	mannosidase					1117:1127	the mannosidase	1113:1127	the mannosidase (N-glycosylation processing enzyme)	1113:1163	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	8	46	theme	processing	1146:1155	arg1	enzyme					1157:1162	N-glycosylation processing enzyme	1130:1162	N-glycosylation processing enzyme	1130:1162	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	2	47	theme	HCC	349:351	arg1	progression					353:363	HCC progression	349:363	HCC progression	349:363	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	0	48	theme	Tyrosine	45:52	arg1	Kinases					54:60	Multiple Receptor Tyrosine Kinases	27:60	Multiple Receptor Tyrosine Kinases	27:60	Involvement of N-glycan in Multiple Receptor Tyrosine Kinases Targeted by Ling-Zhi-8 for Suppressing HCC413 Tumor Progression.
30577605	8	49	theme	enzyme	1082:1087	arg1	PNGase					1089:1094	enzyme PNGase	1082:1094	enzyme PNGase	1082:1094	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	6	50	theme	LZ-8	844:847	arg1	capability					830:839	The capability	826:839	The capability of LZ-8 in targeting multiple RTKs	826:874	The capability of LZ-8 in targeting multiple RTKs was ascribed to its simultaneous binding to these RTKs.
30577605	2	51	theme	Signaling	215:223	arg1	pathways					225:232	Signaling pathways	215:232	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs)	215:290	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	2	51	theme	Signaling	215:223	arg1	targets					323:329	the promising therapeutic targets	297:329	the promising therapeutic targets for prevention of HCC progression	297:363	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	4	52	theme	RTKs	704:707	arg1	activity					684:691	activity	684:691	activity	684:691	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	4	52	theme	RTKs	704:707	arg1	RTKs					704:707	various RTKs	696:707	various RTKs	696:707	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	4	52	theme	RTKs	704:707	arg1	amount					673:678	amount	673:678	amount	673:678	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	10	53	theme	N-glycan	1471:1478	arg1	type					1463:1466	a specific type	1452:1466	a specific type of N-glycan	1452:1478	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	10	53	theme	N-glycan	1471:1478	arg1	target					1497:1502	the potential target	1483:1502	the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression	1483:1568	Our study suggested that a specific type of N-glycan is the potential target for LZ-8 to bind on multiple RTKs for suppressing HCC progression.
30577605	8	54	dep	rescued	1261:1267	arg1	suppressed					1313:1322	suppressed	1313:1322	rescued the downstream signaling and cell migration suppressed by LZ-8	1261:1330	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	4	55	dep	amount	673:678	arg1	the					669:671	the	669:671	the	669:671	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	1	56	theme	poor	131:134	arg1	prognosis					136:144	The poor prognosis	127:144	The poor prognosis of hepatocellular carcinoma (HCC)	127:178	The poor prognosis of hepatocellular carcinoma (HCC) is resulted from tumor metastasis.
30577605	9	57	theme	triggered	1378:1386	arg1	suppression					1388:1398	LZ-8 triggered suppression	1373:1398	LZ-8 triggered suppression of tumor growth of HCC413	1373:1424	Moreover, pretreatment of KIF prevented LZ-8 triggered suppression of tumor growth of HCC413.
30577605	2	58	theme	tyrosine	268:275	arg1	RTKs					286:289	RTKs	286:289	RTKs	286:289	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	2	58	theme	tyrosine	268:275	arg1	kinases					277:283	deregulated receptor tyrosine kinases	247:283	deregulated receptor tyrosine kinases (RTKs)	247:290	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	5	59	theme	downstream	742:751	arg1	signaling					753:761	downstream signaling	742:761	downstream signaling including phosphorylated JNK, ERK involved in HCC progression	742:823	These led to the suppression of downstream signaling including phosphorylated JNK, ERK involved in HCC progression.
30577605	2	60	theme	receptor	259:266	arg1	RTKs					286:289	RTKs	286:289	RTKs	286:289	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	2	60	theme	receptor	259:266	arg1	kinases					277:283	deregulated receptor tyrosine kinases	247:283	deregulated receptor tyrosine kinases (RTKs)	247:290	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	7	61	theme	RTKs	978:981	arg1	motif					969:973	the N-linked glycan motif	949:973	the N-linked glycan motif of RTKs that is required for their maturation and function	949:1032	LZ-8 may bind on the N-linked glycan motif of RTKs that is required for their maturation and function.
30577605	8	62	theme	downstream	1273:1282	arg1	signaling					1284:1292	the downstream signaling	1269:1292	the downstream signaling	1269:1292	Notably, pretreatment of the N-glycan trimming enzyme PNGase or inhibitors of the mannosidase (N-glycosylation processing enzyme), kifunensine (KIF) and swainsonine (SWN), prevented LZ-8 binding on the aforementioned RTKs and rescued the downstream signaling and cell migration suppressed by LZ-8.
30577605	4	63	theme	cell	629:632	arg1	migration					634:642	cell migration	629:642	cell migration of HCC413	629:652	Herein, we report that Ling-Zhi-8 (LZ-8), a medicinal peptide from Ganoderma lucidium, was effective in suppressing cell migration of HCC413, by decreasing the amount and activity of various RTKs.
30577605	5	64	theme	signaling	753:761	arg1	suppression					727:737	the suppression	723:737	the suppression of downstream signaling including phosphorylated JNK, ERK involved in HCC progression	723:823	These led to the suppression of downstream signaling including phosphorylated JNK, ERK involved in HCC progression.
30577605	2	65	theme	deregulated	247:257	arg1	RTKs					286:289	RTKs	286:289	RTKs	286:289	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	2	65	theme	deregulated	247:257	arg1	kinases					277:283	deregulated receptor tyrosine kinases	247:283	deregulated receptor tyrosine kinases (RTKs)	247:290	Signaling pathways triggered by deregulated receptor tyrosine kinases (RTKs) were the promising therapeutic targets for prevention of HCC progression.
30577605	7	66	theme	glycan	962:967	arg1	motif					969:973	the N-linked glycan motif	949:973	the N-linked glycan motif of RTKs that is required for their maturation and function	949:1032	LZ-8 may bind on the N-linked glycan motif of RTKs that is required for their maturation and function.
30577605	1	67	theme	hepatocellular	149:162	arg1	HCC					175:177	HCC	175:177	HCC	175:177	The poor prognosis of hepatocellular carcinoma (HCC) is resulted from tumor metastasis.
30577605	1	67	theme	hepatocellular	149:162	arg1	carcinoma					164:172	hepatocellular carcinoma	149:172	hepatocellular carcinoma (HCC)	149:178	The poor prognosis of hepatocellular carcinoma (HCC) is resulted from tumor metastasis.
30445613	0	0	theme	larval	146:151	arg1	development					153:163	larval development	146:163	larval development	146:163	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	5	1	from	expression	895:904	arg1	oocytes					939:945	oocytes	939:945	oocytes	939:945	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	1	from	expression	895:904	arg1	eggs					951:954	eggs	951:954	eggs	951:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	11	2	theme	gene	1671:1674	arg1	networks					1676:1683	their associated gene networks	1654:1683	their associated gene networks	1654:1683	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	1	3	theme	proteins	231:238	arg1	modification					278:289	the most common post-translational modification	243:289	the most common post-translational modification of proteins	243:301	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	1	3	theme	proteins	231:238	arg1	glycosylation					214:226	N-linked glycosylation	205:226	N-linked glycosylation of proteins	205:238	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	5	4	theme	eggs	876:879	arg1	barriers					864:871	permeation barriers	853:871	permeation barriers of eggs	853:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	8	5	theme	RNAi	1233:1236	arg1	phenotypes					1238:1247	RNAi phenotypes	1233:1247	RNAi phenotypes	1233:1247	By examining RNAi phenotypes, we identified five germline-expressed genes showing similar phenotypes to the algn-7 (RNAi) animals.
30445613	5	6	theme	Endomitotic	761:771	arg1	phenotypes					973:982	the typical phenotypes	961:982	the typical phenotypes observed	961:991	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	6	theme	Endomitotic	761:771	arg1	expression					895:904	abnormal expression	886:904	abnormal expression of chitin and chitin synthase in oocytes and eggs	886:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	6	theme	Endomitotic	761:771	arg1	oocytes					773:779	Endomitotic oocytes	761:779	Endomitotic oocytes	761:779	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	6	theme	Endomitotic	761:771	arg1	fusion					791:796	abnormal fusion	782:796	abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs	782:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	11	7	theme	powerful	1602:1609	arg1	analyses					1563:1570	phenotype analyses	1553:1570	phenotype analyses using the nematode	1553:1589	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	11	7	theme	powerful	1602:1609	arg1	tool					1611:1614	a powerful tool	1600:1614	a powerful tool to detect new CDG candidate genes and their associated gene networks	1600:1683	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	10	8	theme	CDG	1512:1514	arg1	vha-19					1522:1527	vha-19	1522:1527	vha-19	1522:1527	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	10	8	theme	CDG	1512:1514	arg1	gene					1516:1519	a recently found CDG gene	1495:1519	a recently found CDG gene (vha-19)	1495:1528	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	8	9	theme	similar	1302:1308	arg1	phenotypes					1310:1319	similar phenotypes	1302:1319	similar phenotypes	1302:1319	By examining RNAi phenotypes, we identified five germline-expressed genes showing similar phenotypes to the algn-7 (RNAi) animals.
30445613	4	10	theme	gene	609:612	arg1	activity					614:621	The gene activity	605:621	The gene activity	605:621	The gene activity was disrupted by RNAi and deletion mutagenesis, which resulted in larval lethality, defects in oogenesis and oocyte-to-embryo transition.
30445613	10	11	theme	gene	1516:1519	arg1	disorders					1433:1441	known congenital disorders	1416:1441	known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19)	1416:1528	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	10	12	theme	genes	1466:1470	arg1	disorders					1433:1441	known congenital disorders	1416:1441	known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19)	1416:1528	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	4	13	theme	larval	689:694	arg1	lethality					696:704	larval lethality	689:704	larval lethality	689:704	The gene activity was disrupted by RNAi and deletion mutagenesis, which resulted in larval lethality, defects in oogenesis and oocyte-to-embryo transition.
30445613	10	14	dep	genes	1466:1470	arg1	stt-3					1484:1488	stt-3	1484:1488	stt-3	1484:1488	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	10	14	dep	genes	1466:1470	arg1	ribo-1					1473:1478	ribo-1	1473:1478	ribo-1	1473:1478	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	10	14	dep	genes	1466:1470	arg1	genes					1466:1470	glycosylation (CDG) genes	1446:1470	glycosylation (CDG) genes (ribo-1 and stt-3)	1446:1489	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	5	15	theme	abnormal	812:819	arg1	rotation					829:836	abnormal AB cell rotation	812:836	abnormal AB cell rotation	812:836	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	15	theme	abnormal	812:819	arg1	pronuclei					801:809	pronuclei	801:809	pronuclei	801:809	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	10	16	theme	glycosylation	1446:1458	arg1	stt-3					1484:1488	stt-3	1484:1488	stt-3	1484:1488	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	10	16	theme	glycosylation	1446:1458	arg1	ribo-1					1473:1478	ribo-1	1473:1478	ribo-1	1473:1478	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	10	16	theme	glycosylation	1446:1458	arg1	genes					1466:1470	glycosylation (CDG) genes	1446:1470	glycosylation (CDG) genes (ribo-1 and stt-3)	1446:1489	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	2	17	from	lethal	483:488	arg1	mice					493:496	mice	493:496	mice	493:496	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	11	18	theme	new	1626:1628	arg1	genes					1644:1648	new CDG candidate genes	1626:1648	new CDG candidate genes	1626:1648	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	1	19	theme	N-linked	205:212	arg1	modification					278:289	the most common post-translational modification	243:289	the most common post-translational modification of proteins	243:301	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	1	19	theme	N-linked	205:212	arg1	glycosylation					214:226	N-linked glycosylation	205:226	N-linked glycosylation of proteins	205:238	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	0	20	theme	nematode	172:179	arg1	elegans					196:202	the nematode Caenorhabditis elegans	168:202	the nematode Caenorhabditis elegans	168:202	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	2	21	theme	first	419:423	arg1	step					425:428	the first step	415:428	the first step of N-glycosylation	415:447	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	2	22	from	mice	493:496	arg1	lethal					483:488	lethal	483:488	lethal	483:488	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	5	23	theme	chitin	909:914	arg1	synthase					927:934	chitin and chitin synthase	909:934	synthase	927:934	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	8	24	theme	algn-7	1328:1333	arg1	animals					1342:1348	the algn-7 (RNAi) animals	1324:1348	the algn-7 (RNAi) animals	1324:1348	By examining RNAi phenotypes, we identified five germline-expressed genes showing similar phenotypes to the algn-7 (RNAi) animals.
30445613	8	25	theme	germline-expressed	1269:1286	arg1	genes					1288:1292	five germline-expressed genes	1264:1292	five germline-expressed genes showing similar phenotypes to the algn-7 (RNAi) animals	1264:1348	By examining RNAi phenotypes, we identified five germline-expressed genes showing similar phenotypes to the algn-7 (RNAi) animals.
30445613	11	26	theme	CDG	1630:1632	arg1	genes					1644:1648	new CDG candidate genes	1626:1648	new CDG candidate genes	1626:1648	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	1	27	gly	glycosylation	214:226	arg1	proteins					231:238	proteins	231:238	proteins	231:238	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	1	28	theme	common	252:257	arg1	glycosylation					214:226	N-linked glycosylation	205:226	N-linked glycosylation of proteins	205:238	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	1	28	theme	common	252:257	arg1	modification					278:289	the most common post-translational modification	243:289	the most common post-translational modification of proteins	243:301	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	0	29	theme	UDP-N-acetylglucosamine-dolichyl-phosphate	0:41	arg1	N-acetylglucosaminephosphotransferase					43:79	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase	0:79	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase	0:79	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	4	30	theme	deletion	649:656	arg1	mutagenesis					658:668	deletion mutagenesis	649:668	deletion mutagenesis	649:668	The gene activity was disrupted by RNAi and deletion mutagenesis, which resulted in larval lethality, defects in oogenesis and oocyte-to-embryo transition.
30445613	10	31	theme	congenital	1422:1431	arg1	disorders					1433:1441	known congenital disorders	1416:1441	known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19)	1416:1528	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	1	32	theme	post-translational	259:276	arg1	glycosylation					214:226	N-linked glycosylation	205:226	N-linked glycosylation of proteins	205:238	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	1	32	theme	post-translational	259:276	arg1	modification					278:289	the most common post-translational modification	243:289	the most common post-translational modification of proteins	243:301	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	8	33	theme	RNAi	1336:1339	arg1	animals					1342:1348	the algn-7 (RNAi) animals	1324:1348	the algn-7 (RNAi) animals	1324:1348	By examining RNAi phenotypes, we identified five germline-expressed genes showing similar phenotypes to the algn-7 (RNAi) animals.
30445613	7	34	gly	N-glycosylated	1097:1110	arg1	database					1120:1127	an N-glycosylated protein database	1094:1127	an N-glycosylated protein database of C. elegans	1094:1141	We further screened an N-glycosylated protein database of C. elegans, and identified 456 germline-expressed genes coding N-glycosylated proteins.
30445613	0	35	theme	elegans	196:202	arg1	oogenesis					102:110	oogenesis	102:110	oogenesis	102:110	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	0	35	theme	elegans	196:202	arg1	transition					130:139	oocyte-to-embryo transition	113:139	oocyte-to-embryo transition	113:139	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	0	35	theme	elegans	196:202	arg1	development					153:163	larval development	146:163	larval development	146:163	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	5	36	theme	abnormal	886:893	arg1	phenotypes					973:982	the typical phenotypes	961:982	the typical phenotypes observed	961:991	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	36	theme	abnormal	886:893	arg1	expression					895:904	abnormal expression	886:904	abnormal expression of chitin and chitin synthase in oocytes and eggs	886:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	36	theme	abnormal	886:893	arg1	oocytes					773:779	Endomitotic oocytes	761:779	Endomitotic oocytes	761:779	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	36	theme	abnormal	886:893	arg1	fusion					791:796	abnormal fusion	782:796	abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs	782:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	10	37	theme	known	1416:1420	arg1	disorders					1433:1441	known congenital disorders	1416:1441	known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19)	1416:1528	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	3	38	theme	DPAGT1	570:575	arg1	algn-7					549:554	algn-7	549:554	algn-7	549:554	In this study, we identified the sole orthologue (algn-7) of the human DPAGT1 in the nematode C. elegans.
30445613	3	38	theme	DPAGT1	570:575	arg1	orthologue					537:546	the sole orthologue	528:546	the sole orthologue (algn-7) of the human DPAGT1	528:575	In this study, we identified the sole orthologue (algn-7) of the human DPAGT1 in the nematode C. elegans.
30445613	5	39	theme	chitin	920:925	arg1	synthase					927:934	chitin and chitin synthase	909:934	synthase	927:934	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	7	40	theme	germline-expressed	1163:1180	arg1	genes					1182:1186	456 germline-expressed genes	1159:1186	456 germline-expressed genes coding N-glycosylated proteins	1159:1217	We further screened an N-glycosylated protein database of C. elegans, and identified 456 germline-expressed genes coding N-glycosylated proteins.
30445613	0	41	theme	Caenorhabditis	181:194	arg1	elegans					196:202	the nematode Caenorhabditis elegans	168:202	the nematode Caenorhabditis elegans	168:202	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	2	42	theme	N-glycosylation	433:447	arg1	step					425:428	the first step	415:428	the first step of N-glycosylation	415:447	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	3	43	theme	sole	532:535	arg1	algn-7					549:554	algn-7	549:554	algn-7	549:554	In this study, we identified the sole orthologue (algn-7) of the human DPAGT1 in the nematode C. elegans.
30445613	3	43	theme	sole	532:535	arg1	orthologue					537:546	the sole orthologue	528:546	the sole orthologue (algn-7) of the human DPAGT1	528:575	In this study, we identified the sole orthologue (algn-7) of the human DPAGT1 in the nematode C. elegans.
30445613	5	44	theme	AB	821:822	arg1	rotation					829:836	abnormal AB cell rotation	812:836	abnormal AB cell rotation	812:836	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	44	theme	AB	821:822	arg1	pronuclei					801:809	pronuclei	801:809	pronuclei	801:809	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	45	theme	typical	965:971	arg1	phenotypes					973:982	the typical phenotypes	961:982	the typical phenotypes observed	961:991	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	45	theme	typical	965:971	arg1	expression					895:904	abnormal expression	886:904	abnormal expression of chitin and chitin synthase in oocytes and eggs	886:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	45	theme	typical	965:971	arg1	oocytes					773:779	Endomitotic oocytes	761:779	Endomitotic oocytes	761:779	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	45	theme	typical	965:971	arg1	fusion					791:796	abnormal fusion	782:796	abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs	782:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	1	46	theme	proteins	294:301	arg1	glycosylation					214:226	N-linked glycosylation	205:226	N-linked glycosylation of proteins	205:238	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	1	46	theme	proteins	294:301	arg1	modification					278:289	the most common post-translational modification	243:289	the most common post-translational modification of proteins	243:301	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	7	47	theme	N-glycosylated	1195:1208	arg1	proteins					1210:1217	N-glycosylated proteins	1195:1217	N-glycosylated proteins	1195:1217	We further screened an N-glycosylated protein database of C. elegans, and identified 456 germline-expressed genes coding N-glycosylated proteins.
30445613	5	48	from	oocytes	773:779	arg1	oocytes					939:945	oocytes	939:945	oocytes	939:945	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	48	from	oocytes	773:779	arg1	eggs					951:954	eggs	951:954	eggs	951:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	49	theme	cell	824:827	arg1	rotation					829:836	abnormal AB cell rotation	812:836	abnormal AB cell rotation	812:836	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	49	theme	cell	824:827	arg1	pronuclei					801:809	pronuclei	801:809	pronuclei	801:809	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	2	50	theme	UDP-N-acetylglucosamine-dolichyl-phosphate	315:356	arg1	DPAGT1					397:402	DPAGT1	397:402	DPAGT1	397:402	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	2	50	theme	UDP-N-acetylglucosamine-dolichyl-phosphate	315:356	arg1	N-acetylglucosaminephosphotransferase					358:394	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase	304:394	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1)	304:403	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	3	51	theme	human	564:568	arg1	DPAGT1					570:575	the human DPAGT1	560:575	the human DPAGT1	560:575	In this study, we identified the sole orthologue (algn-7) of the human DPAGT1 in the nematode C. elegans.
30445613	0	52	theme	oocyte-to-embryo	113:128	arg1	transition					130:139	oocyte-to-embryo transition	113:139	oocyte-to-embryo transition	113:139	UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase is indispensable for oogenesis, oocyte-to-embryo transition, and larval development of the nematode Caenorhabditis elegans.
30445613	5	53	theme	abnormal	782:789	arg1	phenotypes					973:982	the typical phenotypes	961:982	the typical phenotypes observed	961:991	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	53	theme	abnormal	782:789	arg1	expression					895:904	abnormal expression	886:904	abnormal expression of chitin and chitin synthase in oocytes and eggs	886:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	53	theme	abnormal	782:789	arg1	oocytes					773:779	Endomitotic oocytes	761:779	Endomitotic oocytes	761:779	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	53	theme	abnormal	782:789	arg1	fusion					791:796	abnormal fusion	782:796	abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs	782:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	54	theme	barriers	864:871	arg1	disruption					839:848	disruption	839:848	disruption of permeation barriers of eggs	839:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	54	theme	barriers	864:871	arg1	pronuclei					801:809	pronuclei	801:809	pronuclei	801:809	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	2	55	theme	enzyme	308:313	arg1	DPAGT1					397:402	DPAGT1	397:402	DPAGT1	397:402	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	2	55	theme	enzyme	308:313	arg1	N-acetylglucosaminephosphotransferase					358:394	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase	304:394	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1)	304:403	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	7	56	theme	elegans	1135:1141	arg1	database					1120:1127	an N-glycosylated protein database	1094:1127	an N-glycosylated protein database of C. elegans	1094:1141	We further screened an N-glycosylated protein database of C. elegans, and identified 456 germline-expressed genes coding N-glycosylated proteins.
30445613	3	57	theme	C.	593:594	arg1	elegans					596:602	the nematode C. elegans	580:602	the nematode C. elegans	580:602	In this study, we identified the sole orthologue (algn-7) of the human DPAGT1 in the nematode C. elegans.
30445613	1	58	link	N-linked	205:212	arg1	modification					278:289	the most common post-translational modification	243:289	the most common post-translational modification of proteins	243:301	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	1	58	link	N-linked	205:212	arg1	glycosylation					214:226	N-linked glycosylation	205:226	N-linked glycosylation of proteins	205:238	N-linked glycosylation of proteins is the most common post-translational modification of proteins.
30445613	11	59	theme	candidate	1634:1642	arg1	genes					1644:1648	new CDG candidate genes	1626:1648	new CDG candidate genes	1626:1648	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	11	60	theme	phenotype	1553:1561	arg1	tool					1611:1614	a powerful tool	1600:1614	a powerful tool to detect new CDG candidate genes and their associated gene networks	1600:1683	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	11	60	theme	phenotype	1553:1561	arg1	analyses					1563:1570	phenotype analyses	1553:1570	phenotype analyses using the nematode	1553:1589	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	7	61	theme	protein	1112:1118	arg1	database					1120:1127	an N-glycosylated protein database	1094:1127	an N-glycosylated protein database of C. elegans	1094:1141	We further screened an N-glycosylated protein database of C. elegans, and identified 456 germline-expressed genes coding N-glycosylated proteins.
30445613	10	62	theme	found	1506:1510	arg1	vha-19					1522:1527	vha-19	1522:1527	vha-19	1522:1527	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	10	62	theme	found	1506:1510	arg1	gene					1516:1519	a recently found CDG gene	1495:1519	a recently found CDG gene (vha-19)	1495:1528	We identified known congenital disorders of glycosylation (CDG) genes (ribo-1 and stt-3) and a recently found CDG gene (vha-19).
30445613	5	63	theme	pronuclei	801:809	arg1	phenotypes					973:982	the typical phenotypes	961:982	the typical phenotypes observed	961:991	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	63	theme	pronuclei	801:809	arg1	expression					895:904	abnormal expression	886:904	abnormal expression of chitin and chitin synthase in oocytes and eggs	886:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	63	theme	pronuclei	801:809	arg1	oocytes					773:779	Endomitotic oocytes	761:779	Endomitotic oocytes	761:779	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	63	theme	pronuclei	801:809	arg1	fusion					791:796	abnormal fusion	782:796	abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs	782:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	7	64	theme	N-glycosylated	1097:1110	arg1	database					1120:1127	an N-glycosylated protein database	1094:1127	an N-glycosylated protein database of C. elegans	1094:1141	We further screened an N-glycosylated protein database of C. elegans, and identified 456 germline-expressed genes coding N-glycosylated proteins.
30445613	2	65	theme	knockout	461:468	arg1	DPAGT1					454:459	DPAGT1 knockout	454:468	DPAGT1 knockout	454:468	The enzyme UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) catalyses the first step of N-glycosylation, and DPAGT1 knockout is embryonic lethal in mice.
30445613	5	66	theme	permeation	853:862	arg1	barriers					864:871	permeation barriers	853:871	permeation barriers of eggs	853:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	4	67	theme	oocyte-to-embryo	732:747	arg1	transition					749:758	oocyte-to-embryo transition	732:758	oocyte-to-embryo transition	732:758	The gene activity was disrupted by RNAi and deletion mutagenesis, which resulted in larval lethality, defects in oogenesis and oocyte-to-embryo transition.
30445613	5	68	theme	synthase	927:934	arg1	phenotypes					973:982	the typical phenotypes	961:982	the typical phenotypes observed	961:991	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	68	theme	synthase	927:934	arg1	expression					895:904	abnormal expression	886:904	abnormal expression of chitin and chitin synthase in oocytes and eggs	886:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	68	theme	synthase	927:934	arg1	oocytes					773:779	Endomitotic oocytes	761:779	Endomitotic oocytes	761:779	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	68	theme	synthase	927:934	arg1	fusion					791:796	abnormal fusion	782:796	abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs	782:879	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	7	69	gly	N-glycosylated	1195:1208	arg1	proteins					1210:1217	N-glycosylated proteins	1195:1217	N-glycosylated proteins	1195:1217	We further screened an N-glycosylated protein database of C. elegans, and identified 456 germline-expressed genes coding N-glycosylated proteins.
30445613	3	70	theme	nematode	584:591	arg1	elegans					596:602	the nematode C. elegans	580:602	the nematode C. elegans	580:602	In this study, we identified the sole orthologue (algn-7) of the human DPAGT1 in the nematode C. elegans.
30445613	4	71	from	defects	707:713	arg1	oogenesis					718:726	oogenesis	718:726	oogenesis	718:726	The gene activity was disrupted by RNAi and deletion mutagenesis, which resulted in larval lethality, defects in oogenesis and oocyte-to-embryo transition.
30445613	4	71	from	defects	707:713	arg1	transition					749:758	oocyte-to-embryo transition	732:758	oocyte-to-embryo transition	732:758	The gene activity was disrupted by RNAi and deletion mutagenesis, which resulted in larval lethality, defects in oogenesis and oocyte-to-embryo transition.
30445613	11	72	theme	associated	1660:1669	arg1	networks					1676:1683	their associated gene networks	1654:1683	their associated gene networks	1654:1683	The results show that phenotype analyses using the nematode could be a powerful tool to detect new CDG candidate genes and their associated gene networks.
30445613	5	73	from	fusion	791:796	arg1	oocytes					939:945	oocytes	939:945	oocytes	939:945	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
30445613	5	73	from	fusion	791:796	arg1	eggs					951:954	eggs	951:954	eggs	951:954	Endomitotic oocytes, abnormal fusion of pronuclei, abnormal AB cell rotation, disruption of permeation barriers of eggs, and abnormal expression of chitin and chitin synthase in oocytes and eggs were the typical phenotypes observed.
29917166	7	0	theme	signaling	1170:1178	arg1	pathway					1180:1186	the PI3K signaling pathway	1161:1186	the PI3K signaling pathway	1161:1186	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	6	1	theme	prostate	1000:1007	arg1	lines					1021:1025	two androgen‑independent prostate cancer cell lines	975:1025	two androgen‑independent prostate cancer cell lines	975:1025	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	2	2	link	N‑linked	252:259	arg1	osteopontin					328:338	osteopontin	328:338	osteopontin (OPN)	328:344	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	2	link	N‑linked	252:259	arg1	sialoprotein					305:316	bone sialoprotein	300:316	bone sialoprotein (BSP)	300:322	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	2	link	N‑linked	252:259	arg1	SIBLINGs					276:283	SIBLINGs	276:283	SIBLINGs	276:283	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	2	link	N‑linked	252:259	arg1	glycoproteins					261:273	small integrin‑binding ligand N‑linked glycoproteins	222:273	small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs)	222:284	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	0	3	theme	BSP	76:78	arg1	expression					62:71	the expression	58:71	the expression of BSP, OPN and MMP‑2	58:93	SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP‑2.
29917166	8	4	theme	cells	1481:1485	arg1	proliferation					1448:1460	the proliferation	1444:1460	the proliferation of prostate cancer cells	1444:1485	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	1	5	theme	secondary	143:151	arg1	sites					153:157	secondary sites	143:157	secondary sites	143:157	The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial.
29917166	8	6	theme	cancer	1474:1479	arg1	cells					1481:1485	prostate cancer cells	1465:1485	prostate cancer cells	1465:1485	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	7	7	theme	MMP‑2	1310:1314	arg1	expression					1283:1292	the expression	1279:1292	the expression of BSP, OPN and MMP‑2 in prostate cancer cells	1279:1339	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	0	8	theme	OPN	81:83	arg1	expression					62:71	the expression	58:71	the expression of BSP, OPN and MMP‑2	58:93	SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP‑2.
29917166	7	9	theme	MMP	1233:1235	arg1	proteins					1244:1251	SIBLING and MMP family proteins	1221:1251	proteins	1244:1251	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	5	10	theme	cell	845:848	arg1	invasion ability					850:865	cancer cell invasion ability	838:865	cancer cell invasion ability	838:865	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	5	11	theme	prostate	780:787	arg1	cancer					789:794	prostate cancer	780:794	prostate cancer cell expression of BSP and OPN	780:825	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	5	12	theme	receptor	747:754	arg1	antagonist					756:765	a specific CXCR2 receptor antagonist	730:765	a specific CXCR2 receptor antagonist	730:765	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	5	12	theme	receptor	747:754	arg1	SB225002					720:727	SB225002	720:727	SB225002	720:727	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	6	13	theme	lines	1021:1025	arg1	proliferation					934:946	proliferation	934:946	proliferation	934:946	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	6	13	theme	lines	1021:1025	arg1	migration					962:970	migration	962:970	migration	962:970	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	6	13	theme	lines	1021:1025	arg1	invasion					949:956	invasion	949:956	invasion	949:956	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	3	14	theme	cell	424:427	arg1	invasion					429:436	malignant cell invasion	414:436	malignant cell invasion	414:436	SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP‑2) and MMP‑9 expression.
29917166	0	15	theme	MMP‑2	89:93	arg1	expression					62:71	the expression	58:71	the expression of BSP, OPN and MMP‑2	58:93	SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP‑2.
29917166	5	16	theme	cancer	838:843	arg1	invasion ability					850:865	cancer cell invasion ability	838:865	cancer cell invasion ability	838:865	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	2	17	theme	neoplastic	363:372	arg1	growth					374:379	neoplastic growth	363:379	neoplastic growth	363:379	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	18	gly	glycoproteins	261:273	arg1	osteopontin					328:338	osteopontin	328:338	osteopontin (OPN)	328:344	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	18	gly	glycoproteins	261:273	arg1	sialoprotein					305:316	bone sialoprotein	300:316	bone sialoprotein (BSP)	300:322	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	18	gly	glycoproteins	261:273	arg1	SIBLINGs					276:283	SIBLINGs	276:283	SIBLINGs	276:283	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	18	gly	glycoproteins	261:273	arg1	glycoproteins					261:273	small integrin‑binding ligand N‑linked glycoproteins	222:273	small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs)	222:284	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	6	19	theme	cancer	1118:1123	arg1	cells					1125:1129	androgen‑dependent prostate cancer cells	1090:1129	androgen‑dependent prostate cancer cells	1090:1129	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	7	20	theme	Western	1132:1138	arg1	blotting					1140:1147	Western blotting	1132:1147	Western blotting	1132:1147	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	5	21	theme	BSP	815:817	arg1	expression					801:810	prostate cancer cell expression	780:810	prostate cancer cell expression of BSP and OPN	780:825	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	6	22	theme	prostate	1109:1116	arg1	cells					1125:1129	androgen‑dependent prostate cancer cells	1090:1129	androgen‑dependent prostate cancer cells	1090:1129	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	3	23	theme	malignant	414:422	arg1	invasion					429:436	malignant cell invasion	414:436	malignant cell invasion	414:436	SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP‑2) and MMP‑9 expression.
29917166	0	24	theme	cancer	27:32	arg1	invasion					34:41	prostate cancer invasion	18:41	prostate cancer invasion	18:41	SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP‑2.
29917166	6	25	theme	SB225002	910:917	arg1	treatment					919:927	SB225002 treatment	910:927	SB225002 treatment	910:927	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	8	26	theme	expression	1504:1513	arg1	levels					1515:1520	the expression levels	1500:1520	the expression levels of BSP, OPN and MMP‑2	1500:1542	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	6	27	theme	androgen‑dependent	1090:1107	arg1	cells					1125:1129	androgen‑dependent prostate cancer cells	1090:1129	androgen‑dependent prostate cancer cells	1090:1129	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	7	28	theme	prostate	1319:1326	arg1	cells					1335:1339	prostate cancer cells	1319:1339	prostate cancer cells	1319:1339	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	4	29	theme	tumor	596:600	arg1	surface					607:613	the tumor cell surface	592:613	the tumor cell surface	592:613	Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells.
29917166	0	30	theme	prostate	18:25	arg1	invasion					34:41	prostate cancer invasion	18:41	prostate cancer invasion	18:41	SB225002 inhibits prostate cancer invasion and attenuates the expression of BSP, OPN and MMP‑2.
29917166	8	31	theme	BSP	1525:1527	arg1	levels					1515:1520	the expression levels	1500:1520	the expression levels of BSP, OPN and MMP‑2	1500:1542	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	2	32	theme	bone	300:303	arg1	sialoprotein					305:316	bone sialoprotein	300:316	bone sialoprotein (BSP)	300:322	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	32	theme	bone	300:303	arg1	glycoproteins					261:273	small integrin‑binding ligand N‑linked glycoproteins	222:273	small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs)	222:284	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	32	theme	bone	300:303	arg1	BSP					319:321	BSP	319:321	BSP	319:321	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	4	33	theme	malignant	639:647	arg1	behavior					649:656	the malignant behavior	635:656	the malignant behavior of tumor cells	635:671	Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells.
29917166	7	34	theme	proteins	1244:1251	arg1	expression					1207:1216	the expression	1203:1216	the expression of SIBLING and MMP family proteins	1203:1251	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	6	35	theme	androgen‑independent	979:998	arg1	lines					1021:1025	two androgen‑independent prostate cancer cell lines	975:1025	two androgen‑independent prostate cancer cell lines	975:1025	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	2	36	theme	integrin‑binding	228:243	arg1	osteopontin					328:338	osteopontin	328:338	osteopontin (OPN)	328:344	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	36	theme	integrin‑binding	228:243	arg1	sialoprotein					305:316	bone sialoprotein	300:316	bone sialoprotein (BSP)	300:322	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	36	theme	integrin‑binding	228:243	arg1	SIBLINGs					276:283	SIBLINGs	276:283	SIBLINGs	276:283	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	36	theme	integrin‑binding	228:243	arg1	glycoproteins					261:273	small integrin‑binding ligand N‑linked glycoproteins	222:273	small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs)	222:284	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	6	37	theme	cell	1016:1019	arg1	lines					1021:1025	two androgen‑independent prostate cancer cell lines	975:1025	two androgen‑independent prostate cancer cell lines	975:1025	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	5	38	theme	cancer	789:794	arg1	expression					801:810	prostate cancer cell expression	780:810	prostate cancer cell expression of BSP and OPN	780:825	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	8	39	theme	OPN	1530:1532	arg1	levels					1515:1520	the expression levels	1500:1520	the expression levels of BSP, OPN and MMP‑2	1500:1542	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	2	40	theme	small	222:226	arg1	osteopontin					328:338	osteopontin	328:338	osteopontin (OPN)	328:344	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	40	theme	small	222:226	arg1	sialoprotein					305:316	bone sialoprotein	300:316	bone sialoprotein (BSP)	300:322	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	40	theme	small	222:226	arg1	SIBLINGs					276:283	SIBLINGs	276:283	SIBLINGs	276:283	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	40	theme	small	222:226	arg1	glycoproteins					261:273	small integrin‑binding ligand N‑linked glycoproteins	222:273	small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs)	222:284	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	4	41	theme	cell	602:605	arg1	surface					607:613	the tumor cell surface	592:613	the tumor cell surface	592:613	Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells.
29917166	5	42	theme	specific	732:739	arg1	antagonist					756:765	a specific CXCR2 receptor antagonist	730:765	a specific CXCR2 receptor antagonist	730:765	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	5	42	theme	specific	732:739	arg1	SB225002					720:727	SB225002	720:727	SB225002	720:727	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	5	43	theme	OPN	823:825	arg1	expression					801:810	prostate cancer cell expression	780:810	prostate cancer cell expression of BSP and OPN	780:825	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	7	44	theme	BSP	1297:1299	arg1	expression					1283:1292	the expression	1279:1292	the expression of BSP, OPN and MMP‑2 in prostate cancer cells	1279:1339	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	7	45	theme	PI3K	1165:1168	arg1	pathway					1180:1186	the PI3K signaling pathway	1161:1186	the PI3K signaling pathway	1161:1186	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	4	46	located	located	581:587	arg1	surface					607:613	the tumor cell surface	592:613	the tumor cell surface	592:613	Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells.
29917166	4	46	located	located	581:587	arg2	integrin					562:569	integrin	562:569	integrin	562:569	Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells.
29917166	6	47	theme	inhibitory	1052:1061	arg1	effect					1063:1068	this inhibitory effect	1047:1068	this inhibitory effect	1047:1068	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	4	48	theme	cells	667:671	arg1	behavior					649:656	the malignant behavior	635:656	the malignant behavior of tumor cells	635:671	Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells.
29917166	5	49	theme	CXCR2	741:745	arg1	antagonist					756:765	a specific CXCR2 receptor antagonist	730:765	a specific CXCR2 receptor antagonist	730:765	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	5	49	theme	CXCR2	741:745	arg1	SB225002					720:727	SB225002	720:727	SB225002	720:727	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	8	50	theme	MMP‑2	1538:1542	arg1	levels					1515:1520	the expression levels	1500:1520	the expression levels of BSP, OPN and MMP‑2	1500:1542	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	1	51	theme	metastasis	129:138	arg1	complex					163:169	complex	163:169	complex	163:169	The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial.
29917166	1	51	theme	metastasis	129:138	arg1	mechanisms					100:109	The mechanisms	96:109	The mechanisms of malignant cell metastasis to secondary sites	96:157	The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial.
29917166	7	52	theme	family	1237:1242	arg1	proteins					1244:1251	SIBLING and MMP family proteins	1221:1251	proteins	1244:1251	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	4	53	theme	tumor	661:665	arg1	cells					667:671	tumor cells	661:671	tumor cells	661:671	Moreover, BSP and OPN can combine with integrin, which is located on the tumor cell surface, to further promote the malignant behavior of tumor cells.
29917166	8	54	theme	in vivo	1390:1396	arg1	experiments					1398:1408	in vivo experiments	1390:1408	in vivo experiments	1390:1408	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	7	55	theme	SIBLING	1221:1227	arg1	proteins					1244:1251	SIBLING and MMP family proteins	1221:1251	proteins	1244:1251	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	6	56	located	observed	1078:1085	arg2	effect					1063:1068	this inhibitory effect	1047:1068	this inhibitory effect	1047:1068	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	6	56	located	observed	1078:1085	arg1	cells					1125:1129	androgen‑dependent prostate cancer cells	1090:1129	androgen‑dependent prostate cancer cells	1090:1129	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	7	57	theme	OPN	1302:1304	arg1	expression					1283:1292	the expression	1279:1292	the expression of BSP, OPN and MMP‑2 in prostate cancer cells	1279:1339	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	7	58	theme	cancer	1328:1333	arg1	cells					1335:1339	prostate cancer cells	1319:1339	prostate cancer cells	1319:1339	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	3	59	theme	matrix	466:471	arg1	metalloproteinase					473:489	matrix metalloproteinase 2	466:491	matrix metalloproteinase 2 (MMP‑2)	466:499	SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP‑2) and MMP‑9 expression.
29917166	3	59	theme	matrix	466:471	arg1	MMP‑2					494:498	MMP‑2	494:498	MMP‑2	494:498	SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP‑2) and MMP‑9 expression.
29917166	7	60	theme	AKT/mTOR	1355:1362	arg1	phosphorylation					1364:1378	AKT/mTOR phosphorylation	1355:1378	AKT/mTOR phosphorylation	1355:1378	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	1	61	theme	malignant	114:122	arg1	metastasis					129:138	malignant cell metastasis	114:138	malignant cell metastasis to secondary sites	114:157	The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial.
29917166	5	62	theme	cell	796:799	arg1	expression					801:810	prostate cancer cell expression	780:810	prostate cancer cell expression of BSP and OPN	780:825	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
29917166	2	63	theme	N‑linked	252:259	arg1	osteopontin					328:338	osteopontin	328:338	osteopontin (OPN)	328:344	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	63	theme	N‑linked	252:259	arg1	sialoprotein					305:316	bone sialoprotein	300:316	bone sialoprotein (BSP)	300:322	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	63	theme	N‑linked	252:259	arg1	SIBLINGs					276:283	SIBLINGs	276:283	SIBLINGs	276:283	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	63	theme	N‑linked	252:259	arg1	glycoproteins					261:273	small integrin‑binding ligand N‑linked glycoproteins	222:273	small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs)	222:284	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	6	64	theme	cancer	1009:1014	arg1	lines					1021:1025	two androgen‑independent prostate cancer cell lines	975:1025	two androgen‑independent prostate cancer cell lines	975:1025	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	1	65	theme	cell	124:127	arg1	metastasis					129:138	malignant cell metastasis	114:138	malignant cell metastasis to secondary sites	114:157	The mechanisms of malignant cell metastasis to secondary sites are complex and multifactorial.
29917166	8	66	theme	prostate	1465:1472	arg1	cells					1481:1485	prostate cancer cells	1465:1485	prostate cancer cells	1465:1485	Finally, in vivo experiments confirmed that SB225002 inhibited the proliferation of prostate cancer cells in vivo, and the expression levels of BSP, OPN and MMP‑2 were also inhibited.
29917166	2	67	theme	ligand	245:250	arg1	osteopontin					328:338	osteopontin	328:338	osteopontin (OPN)	328:344	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	67	theme	ligand	245:250	arg1	sialoprotein					305:316	bone sialoprotein	300:316	bone sialoprotein (BSP)	300:322	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	67	theme	ligand	245:250	arg1	SIBLINGs					276:283	SIBLINGs	276:283	SIBLINGs	276:283	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	2	67	theme	ligand	245:250	arg1	glycoproteins					261:273	small integrin‑binding ligand N‑linked glycoproteins	222:273	small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs)	222:284	Studies have demonstrated that small integrin‑binding ligand N‑linked glycoproteins (SIBLINGs), particularly bone sialoprotein (BSP) and osteopontin (OPN), are involved in neoplastic growth and metastasis.
29917166	7	68	from	expression	1283:1292	arg1	cells					1335:1339	prostate cancer cells	1319:1339	prostate cancer cells	1319:1339	Western blotting showed that the PI3K signaling pathway could regulate the expression of SIBLING and MMP family proteins, and SB22055 could reduce the expression of BSP, OPN and MMP‑2 in prostate cancer cells by inhibiting AKT/mTOR phosphorylation.
29917166	3	69	theme	MMP‑9	505:509	arg1	expression					511:520	MMP‑9 expression	505:520	MMP‑9 expression	505:520	SIBLINGs promote malignant cell invasion and metastasis by enhancing matrix metalloproteinase 2 (MMP‑2) and MMP‑9 expression.
29917166	6	70	theme	experiments	880:890	arg1	series					870:875	A series	868:875	A series of experiments	868:890	A series of experiments showed that after SB225002 treatment, the proliferation, invasion and migration of two androgen‑independent prostate cancer cell lines were inhibited, but this inhibitory effect was not observed on androgen‑dependent prostate cancer cells.
29917166	5	71	theme	present	681:687	arg1	study					689:693	the present study	677:693	the present study	677:693	In the present study, we investigated whether SB225002, a specific CXCR2 receptor antagonist, can inhibit prostate cancer cell expression of BSP and OPN and reduce cancer cell invasion ability.
30625365	0	0	theme	O-GlcNAc	71:78	arg1	homeostasis					80:90	O-GlcNAc homeostasis	71:90	O-GlcNAc homeostasis	71:90	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
30625365	6	1	theme	protein	1014:1020	arg1	O-GlcNAcylation					1022:1036	protein O-GlcNAcylation	1014:1036	protein O-GlcNAcylation	1014:1036	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	1	2	theme	Temporal	146:153	arg1	TLE					170:172	TLE	170:172	TLE	170:172	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	1	2	theme	Temporal	146:153	arg1	Epilepsy					160:167	Temporal Lobe Epilepsy	146:167	Temporal Lobe Epilepsy (TLE)	146:173	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	7	3	theme	O-GlcNAc	1208:1215	arg1	homeostasis					1217:1227	O-GlcNAc homeostasis	1208:1227	O-GlcNAc homeostasis	1208:1227	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	1	4	theme	Lobe	155:158	arg1	TLE					170:172	TLE	170:172	TLE	170:172	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	1	4	theme	Lobe	155:158	arg1	Epilepsy					160:167	Temporal Lobe Epilepsy	146:167	Temporal Lobe Epilepsy (TLE)	146:173	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	4	5	from	O-GlcNAcylation	672:686	arg1	hippocampus					705:715	the epileptic hippocampus	691:715	the epileptic hippocampus	691:715	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	1	6	theme	post-translational	240:257	arg1	PTM					274:276	PTM	274:276	PTM	274:276	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	1	6	theme	post-translational	240:257	arg1	modifications					259:271	post-translational modifications	240:271	post-translational modifications (PTM) that exacerbate the disorder	240:306	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	7	7	theme	pathways	1317:1324	arg1	targeting					1287:1295	targeting	1287:1295	targeting of O-GlcNAc related pathways	1287:1324	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	5	8	theme	TLE	951:953	arg1	tissue					967:972	human TLE hippocampal tissue	945:972	human TLE hippocampal tissue	945:972	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	6	9	theme	therapeutic	1132:1142	arg1	target					1144:1149	a therapeutic target	1130:1149	a therapeutic target for seizure control	1130:1169	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	6	9	theme	therapeutic	1132:1142	arg1	OGA					1119:1121	OGA	1119:1121	OGA	1119:1121	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	5	10	theme	TLE	934:936	arg1	model					925:929	the kainate rat model	909:929	the kainate rat model of TLE	909:936	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	5	11	theme	hippocampal	955:965	arg1	tissue					967:972	human TLE hippocampal tissue	945:972	human TLE hippocampal tissue	945:972	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	6	12	theme	Inhibiting	975:984	arg1	OGA					986:988	Inhibiting OGA	975:988	Inhibiting OGA with Thiamet-G	975:1003	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	5	13	from	expression	895:904	arg1	tissue					967:972	human TLE hippocampal tissue	945:972	human TLE hippocampal tissue	945:972	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	5	13	from	expression	895:904	arg1	model					925:929	the kainate rat model	909:929	the kainate rat model of TLE	909:936	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	4	14	theme	proteins	775:782	arg1	PTM					788:790	PTM's	788:792	PTM's	788:792	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	4	14	theme	proteins	775:782	arg1	manipulation					753:764	direct manipulation	746:764	direct manipulation of these proteins	746:782	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	4	15	from	OGT/OGA	652:658	arg1	hippocampus					705:715	the epileptic hippocampus	691:715	the epileptic hippocampus	691:715	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	6	16	theme	spike	1089:1093	arg1	events					1095:1100	epileptic spike events	1079:1100	epileptic spike events	1079:1100	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	5	17	theme	specific	862:869	arg1	O-GlcNAcylation					871:885	O-GlcNAcylation	871:885	O-GlcNAcylation	871:885	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	2	18	theme	metabolic	449:457	arg1	substrates					459:468	metabolic substrates	449:468	metabolic substrates	449:468	O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates.
30625365	6	19	theme	seizure	1155:1161	arg1	control					1163:1169	seizure control	1155:1169	seizure control	1155:1169	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	7	20	theme	homeostasis	1217:1227	arg1	loss					1200:1203	loss	1200:1203	loss of O-GlcNAc homeostasis in the kainate model and in human TLE	1200:1265	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	2	21	theme	O-linked-β-N-acetyl	309:327	arg1	O-GlcNAc					342:349	O-GlcNAc	342:349	O-GlcNAc	342:349	O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates.
30625365	2	21	theme	O-linked-β-N-acetyl	309:327	arg1	glucosamine					329:339	O-linked-β-N-acetyl glucosamine	309:339	O-linked-β-N-acetyl glucosamine (O-GlcNAc)	309:350	O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates.
30625365	2	21	theme	O-linked-β-N-acetyl	309:327	arg1	PTM					357:359	a PTM	355:359	a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates	355:468	O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates.
30625365	2	22	theme	serine/threonine	374:389	arg1	residues					391:398	serine/threonine residues	374:398	serine/threonine residues	374:398	O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates.
30625365	0	23	theme	Human	0:4	arg1	epilepsy					31:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
30625365	7	24	theme	related	1309:1315	arg1	pathways					1317:1324	O-GlcNAc related pathways	1300:1324	O-GlcNAc related pathways	1300:1324	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	0	25	theme	temporal	17:24	arg1	epilepsy					31:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
30625365	4	26	theme	direct	746:751	arg1	manipulation					753:764	direct manipulation	746:764	direct manipulation of these proteins	746:782	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	6	27	theme	seizure	1058:1064	arg1	duration					1066:1073	seizure duration	1058:1073	seizure duration	1058:1073	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	0	28	theme	rodent	10:15	arg1	epilepsy					31:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
30625365	5	29	theme	human	945:949	arg1	tissue					967:972	human TLE hippocampal tissue	945:972	human TLE hippocampal tissue	945:972	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	5	30	theme	reduced	835:841	arg1	expression					895:904	reduced global and protein specific O-GlcNAcylation and OGT expression	835:904	reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue	835:972	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	5	31	theme	rat	921:923	arg1	model					925:929	the kainate rat model	909:929	the kainate rat model of TLE	909:936	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	0	32	theme	epileptiform	123:134	arg1	activity					136:143	epileptiform activity	123:143	epileptiform activity	123:143	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
30625365	5	33	theme	global	843:848	arg1	O-GlcNAcylation					871:885	O-GlcNAcylation	871:885	O-GlcNAcylation	871:885	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	0	34	theme	lobe	26:29	arg1	epilepsy					31:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy	0:38	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
30625365	5	35	theme	O-GlcNAcylation	871:885	arg1	expression					895:904	reduced global and protein specific O-GlcNAcylation and OGT expression	835:904	reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue	835:972	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	0	36	from	changes	60:66	arg1	homeostasis					80:90	O-GlcNAc homeostasis	71:90	O-GlcNAc homeostasis	71:90	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.
30625365	4	37	theme	epileptiform	800:811	arg1	activity					813:820	epileptiform activity	800:820	epileptiform activity	800:820	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	4	38	theme	study	626:630	arg1	goal					613:616	The goal	609:616	The goal of this study	609:630	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	5	39	theme	kainate	913:919	arg1	model					925:929	the kainate rat model	909:929	the kainate rat model of TLE	909:936	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	4	40	theme	epileptic	695:703	arg1	hippocampus					705:715	the epileptic hippocampus	691:715	the epileptic hippocampus	691:715	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	1	41	from	changes	205:211	arg1	PTM					274:276	PTM	274:276	PTM	274:276	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	1	41	from	changes	205:211	arg1	composition					224:234	protein composition	216:234	protein composition	216:234	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	1	41	from	changes	205:211	arg1	modifications					259:271	post-translational modifications	240:271	post-translational modifications (PTM) that exacerbate the disorder	240:306	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	6	42	with	OGA	986:988	arg1	Thiamet-G					995:1003	Thiamet-G	995:1003	Thiamet-G	995:1003	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	3	43	theme	O-GlcNAc	586:593	arg1	modification					595:606	the O-GlcNAc modification	582:606	the O-GlcNAc modification	582:606	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	7	44	theme	human	1257:1261	arg1	TLE					1263:1265	human TLE	1257:1265	human TLE	1257:1265	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	7	45	from	loss	1200:1203	arg1	TLE					1263:1265	human TLE	1257:1265	human TLE	1257:1265	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	7	45	from	loss	1200:1203	arg1	model					1244:1248	the kainate model	1232:1248	the kainate model	1232:1248	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	3	46	dep	addition	543:550	arg1	the					539:541	the	539:541	the	539:541	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	7	47	theme	O-GlcNAc	1300:1307	arg1	pathways					1317:1324	O-GlcNAc related pathways	1300:1324	O-GlcNAc related pathways	1300:1324	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
30625365	3	48	theme	modification	595:606	arg1	removal					556:562	removal	556:562	removal	556:562	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	3	48	theme	modification	595:606	arg1	addition					543:550	addition	543:550	addition	543:550	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	5	49	theme	OGT	891:893	arg1	expression					895:904	reduced global and protein specific O-GlcNAcylation and OGT expression	835:904	reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue	835:972	We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue.
30625365	6	50	theme	epileptic	1079:1087	arg1	events					1095:1100	epileptic spike events	1079:1100	epileptic spike events	1079:1100	Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control.
30625365	1	51	theme	protein	216:222	arg1	composition					224:234	protein composition	216:234	protein composition	216:234	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder.
30625365	3	52	dep	enzymes	475:481	arg1	OGT					504:506	OGT	504:506	OGT	504:506	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	3	52	dep	enzymes	475:481	arg1	O-GlcNAcase					513:523	O-GlcNAcase	513:523	O-GlcNAcase (OGA)	513:529	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	3	52	dep	enzymes	475:481	arg1	O-GlcNActransferase					483:501	O-GlcNActransferase	483:501	O-GlcNActransferase (OGT)	483:507	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	3	52	dep	enzymes	475:481	arg1	enzymes					475:481	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA)	471:529	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA)	471:529	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	3	52	dep	enzymes	475:481	arg1	OGA					526:528	OGA	526:528	OGA	526:528	The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification.
30625365	4	53	theme	protein	664:670	arg1	O-GlcNAcylation					672:686	protein O-GlcNAcylation	664:686	protein O-GlcNAcylation	664:686	The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity.
30625365	7	54	theme	kainate	1236:1242	arg1	model					1244:1248	the kainate model	1232:1248	the kainate model	1232:1248	These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.
29460617	0	0	theme	mTOR-Independent	81:96	arg1	Pathway					98:104	an mTOR-Independent Pathway	78:104	an mTOR-Independent Pathway	78:104	Pharmacological Inhibition of O-GlcNAcase Enhances Autophagy in Brain through an mTOR-Independent Pathway.
29460617	10	1	theme	other	1729:1733	arg1	diseases					1753:1760	other neurodegenerative diseases	1729:1760	other neurodegenerative diseases	1729:1760	Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases.
29460617	4	2	theme	amyloid	734:740	arg1	pathology					742:750	amyloid pathology	734:750	amyloid pathology	734:750	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	11	3	theme	mTOR-independent	1846:1861	arg1	manner					1863:1868	an mTOR-independent manner	1843:1868	an mTOR-independent manner	1843:1868	Moreover, these data suggest more targeted strategies to stimulate autophagy in an mTOR-independent manner may be found within the O-GlcNAc pathway.
29460617	7	4	theme	OGA	1126:1128	arg1	inhibitors					1130:1139	selective OGA inhibitors	1116:1139	selective OGA inhibitors	1116:1139	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	9	5	theme	protein	1600:1606	arg1	species					1608:1614	toxic protein species	1594:1614	toxic protein species	1594:1614	These results strongly suggest that OGA inhibitors act within brain through a mechanism involving enhancement of autophagy, which aids the brain in combatting the accumulation of toxic protein species.
29460617	11	6	dep	suggest	1784:1790	arg1	found					1877:1881	found	1877:1881	suggest more targeted strategies to stimulate autophagy in an mTOR-independent manner may be found within the O-GlcNAc pathway	1784:1909	Moreover, these data suggest more targeted strategies to stimulate autophagy in an mTOR-independent manner may be found within the O-GlcNAc pathway.
29460617	8	7	from	pathogenesis	1331:1342	arg1	model					1373:1377	the JNPL3 tauopathy mouse model	1347:1377	the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1347:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	8	7	from	pathogenesis	1331:1342	arg1	model					1408:1412	the 3×Tg-AD mouse model	1390:1412	the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1347:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	8	8	theme	3×Tg-AD	1394:1400	arg1	model					1408:1412	the 3×Tg-AD mouse model	1390:1412	the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1347:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	9	9	theme	toxic	1594:1598	arg1	species					1608:1614	toxic protein species	1594:1614	toxic protein species	1594:1614	These results strongly suggest that OGA inhibitors act within brain through a mechanism involving enhancement of autophagy, which aids the brain in combatting the accumulation of toxic protein species.
29460617	2	10	theme	gene	363:366	arg1	expression					368:377	gene expression	363:377	gene expression	363:377	O-GlcNAc is involved in diverse cellular processes ranging from the regulation of gene expression to stress response.
29460617	5	11	theme	OGA-selective	817:829	arg1	inhibitors					831:840	OGA-selective inhibitors	817:840	OGA-selective inhibitors as pharmaceuticals	817:859	These data have stimulated interest in the possibility of using OGA-selective inhibitors as pharmaceuticals to alter the progression of AD.
29460617	2	12	theme	stress	382:387	arg1	response					389:396	stress response	382:396	stress response	382:396	O-GlcNAc is involved in diverse cellular processes ranging from the regulation of gene expression to stress response.
29460617	12	13	theme	inhibitors	1961:1970	arg1	advancement					1942:1952	the advancement	1938:1952	the advancement of OGA inhibitors within the clinic	1938:1988	These findings should aid the advancement of OGA inhibitors within the clinic.
29460617	4	14	theme	disease	682:688	arg1	models					701:706	various Alzheimer's disease (AD) mouse models	662:706	various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology	662:750	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	2	15	theme	cellular	313:320	arg1	processes					322:330	diverse cellular processes	305:330	diverse cellular processes ranging from the regulation of gene expression to stress response	305:396	O-GlcNAc is involved in diverse cellular processes ranging from the regulation of gene expression to stress response.
29460617	8	16	theme	species	1304:1310	arg1	levels					1280:1285	the levels	1276:1285	the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1276:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	7	17	from	range	1022:1026	arg1	brain					1104:1108	mouse brain	1098:1108	mouse brain	1098:1108	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	7	17	from	range	1022:1026	arg1	neurons					1082:1088	primary rat neurons	1070:1088	primary rat neurons	1070:1088	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	7	17	from	range	1022:1026	arg1	cells					1060:1064	neuroblastoma N2a cells	1042:1064	neuroblastoma N2a cells	1042:1064	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	1	18	gly	glycosylation	111:123	arg1	proteins					146:153	nucleocytoplasmic proteins	128:153	nucleocytoplasmic proteins	128:153	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	0	19	from	Autophagy	51:59	arg1	Brain					64:68	Brain	64:68	Brain	64:68	Pharmacological Inhibition of O-GlcNAcase Enhances Autophagy in Brain through an mTOR-Independent Pathway.
29460617	7	20	theme	selective	1116:1124	arg1	inhibitors					1130:1139	selective OGA inhibitors	1116:1139	selective OGA inhibitors	1116:1139	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	2	21	theme	diverse	305:311	arg1	processes					322:330	diverse cellular processes	305:330	diverse cellular processes ranging from the regulation of gene expression to stress response	305:396	O-GlcNAc is involved in diverse cellular processes ranging from the regulation of gene expression to stress response.
29460617	3	22	theme	cardiac	481:487	arg1	dysfunction					489:499	cardiac dysfunction	481:499	cardiac dysfunction	481:499	Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases.
29460617	1	23	with	glycosylation	111:123	arg1	residues					189:196	O-linked N-acetylglucosamine residues	160:196	O-linked N-acetylglucosamine residues (O-GlcNAc)	160:207	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	1	23	with	glycosylation	111:123	arg1	O-GlcNAc					199:206	O-GlcNAc	199:206	O-GlcNAc	199:206	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	4	24	theme	Pharmacological	534:548	arg1	inhibition					550:559	Pharmacological inhibition	534:559	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc,	534:620	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	9	25	theme	species	1608:1614	arg1	accumulation					1578:1589	the accumulation	1574:1589	the accumulation of toxic protein species	1574:1614	These results strongly suggest that OGA inhibitors act within brain through a mechanism involving enhancement of autophagy, which aids the brain in combatting the accumulation of toxic protein species.
29460617	6	26	theme	inhibitors	953:962	arg1	effects					938:944	the neuroprotective effects	918:944	the neuroprotective effects of OGA inhibitors	918:962	The mechanisms mediating the neuroprotective effects of OGA inhibitors, however, remain poorly understood.
29460617	7	27	from	methods	1031:1037	arg1	brain					1104:1108	mouse brain	1098:1108	mouse brain	1098:1108	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	7	27	from	methods	1031:1037	arg1	neurons					1082:1088	primary rat neurons	1070:1088	primary rat neurons	1070:1088	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	7	27	from	methods	1031:1037	arg1	cells					1060:1064	neuroblastoma N2a cells	1042:1064	neuroblastoma N2a cells	1042:1064	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	0	28	theme	Pharmacological	0:14	arg1	Inhibition					16:25	Pharmacological Inhibition	0:25	Pharmacological Inhibition of O-GlcNAcase	0:40	Pharmacological Inhibition of O-GlcNAcase Enhances Autophagy in Brain through an mTOR-Independent Pathway.
29460617	7	29	from	brain	1104:1108	arg1	range					1022:1026	a range	1020:1026	a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain	1020:1108	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	10	30	theme	diseases	1753:1760	arg1	progression					1707:1717	the progression	1703:1717	the progression of AD and other neurodegenerative diseases	1703:1760	Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases.
29460617	8	31	theme	mouse	1402:1406	arg1	model					1408:1412	the 3×Tg-AD mouse model	1390:1412	the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1347:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	8	32	theme	protein	1296:1302	arg1	species					1304:1310	toxic protein species	1290:1310	toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1290:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	0	33	theme	O-GlcNAcase	30:40	arg1	Inhibition					16:25	Pharmacological Inhibition	0:25	Pharmacological Inhibition of O-GlcNAcase	0:40	Pharmacological Inhibition of O-GlcNAcase Enhances Autophagy in Brain through an mTOR-Independent Pathway.
29460617	8	34	theme	JNPL3	1351:1355	arg1	model					1373:1377	the JNPL3 tauopathy mouse model	1347:1377	the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1347:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	5	35	theme	AD	889:890	arg1	progression					874:884	the progression	870:884	the progression of AD	870:890	These data have stimulated interest in the possibility of using OGA-selective inhibitors as pharmaceuticals to alter the progression of AD.
29460617	7	36	theme	obvious	1205:1211	arg1	toxicity					1213:1220	obvious toxicity	1205:1220	obvious toxicity	1205:1220	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	7	37	theme	mouse	1098:1102	arg1	brain					1104:1108	mouse brain	1098:1108	mouse brain	1098:1108	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	3	38	theme	neurodegenerative	506:522	arg1	diseases					524:531	neurodegenerative diseases	506:531	neurodegenerative diseases	506:531	Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases.
29460617	7	39	theme	mTOR-independent	1172:1187	arg1	pathway					1189:1195	an mTOR-independent pathway	1169:1195	an mTOR-independent pathway without obvious toxicity	1169:1220	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	6	40	theme	neuroprotective	922:936	arg1	effects					938:944	the neuroprotective effects	918:944	the neuroprotective effects of OGA inhibitors	918:962	The mechanisms mediating the neuroprotective effects of OGA inhibitors, however, remain poorly understood.
29460617	7	41	from	cells	1060:1064	arg1	range					1022:1026	a range	1020:1026	a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain	1020:1108	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	8	42	theme	toxic	1290:1294	arg1	species					1304:1310	toxic protein species	1290:1310	toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1290:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	11	43	theme	O-GlcNAc	1894:1901	arg1	pathway					1903:1909	the O-GlcNAc pathway	1890:1909	the O-GlcNAc pathway	1890:1909	Moreover, these data suggest more targeted strategies to stimulate autophagy in an mTOR-independent manner may be found within the O-GlcNAc pathway.
29460617	8	44	theme	AD	1328:1329	arg1	pathogenesis					1331:1342	AD pathogenesis	1328:1342	AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1328:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	3	45	theme	various	435:441	arg1	diseases					443:450	various diseases	435:450	various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases	435:531	Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases.
29460617	3	45	theme	various	435:441	arg1	diseases					524:531	neurodegenerative diseases	506:531	neurodegenerative diseases	506:531	Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases.
29460617	3	45	theme	various	435:441	arg1	diabetes					471:478	diabetes	471:478	diabetes	471:478	Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases.
29460617	3	45	theme	various	435:441	arg1	dysfunction					489:499	cardiac dysfunction	481:499	cardiac dysfunction	481:499	Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases.
29460617	3	45	theme	various	435:441	arg1	cancers					462:468	cancers	462:468	cancers	462:468	Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases.
29460617	7	46	theme	rat	1078:1080	arg1	neurons					1082:1088	primary rat neurons	1070:1088	primary rat neurons	1070:1088	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	9	47	theme	autophagy	1528:1536	arg1	enhancement					1513:1523	enhancement	1513:1523	enhancement	1513:1523	These results strongly suggest that OGA inhibitors act within brain through a mechanism involving enhancement of autophagy, which aids the brain in combatting the accumulation of toxic protein species.
29460617	6	48	theme	OGA	949:951	arg1	inhibitors					953:962	OGA inhibitors	949:962	OGA inhibitors	949:962	The mechanisms mediating the neuroprotective effects of OGA inhibitors, however, remain poorly understood.
29460617	1	49	theme	nucleocytoplasmic	128:144	arg1	proteins					146:153	nucleocytoplasmic proteins	128:153	nucleocytoplasmic proteins	128:153	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	10	50	theme	feasible	1659:1666	arg1	strategy					1680:1687	a feasible therapeutic strategy	1657:1687	a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases	1657:1760	Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases.
29460617	4	51	theme	sole	587:590	arg1	O-GlcNAcase					564:574	O-GlcNAcase	564:574	O-GlcNAcase (OGA)	564:580	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	4	51	theme	sole	587:590	arg1	enzyme					592:597	the sole enzyme	583:597	the sole enzyme that removes O-GlcNAc	583:619	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	1	52	link	O-linked	160:167	arg1	residues					189:196	O-linked N-acetylglucosamine residues	160:196	O-linked N-acetylglucosamine residues (O-GlcNAc)	160:207	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	1	52	link	O-linked	160:167	arg1	O-GlcNAc					199:206	O-GlcNAc	199:206	O-GlcNAc	199:206	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	12	53	theme	OGA	1957:1959	arg1	inhibitors					1961:1970	OGA inhibitors	1957:1970	OGA inhibitors	1957:1970	These findings should aid the advancement of OGA inhibitors within the clinic.
29460617	7	54	theme	neuroblastoma	1042:1054	arg1	cells					1060:1064	neuroblastoma N2a cells	1042:1064	neuroblastoma N2a cells	1042:1064	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	1	55	theme	proteins	146:153	arg1	abundant					258:265	abundant	258:265	abundant	258:265	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	1	55	theme	proteins	146:153	arg1	glycosylation					111:123	The glycosylation	107:123	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc)	107:207	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	7	56	theme	N2a	1056:1058	arg1	cells					1060:1064	neuroblastoma N2a cells	1042:1064	neuroblastoma N2a cells	1042:1064	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	2	57	theme	expression	368:377	arg1	regulation					349:358	the regulation	345:358	the regulation of gene expression	345:377	O-GlcNAc is involved in diverse cellular processes ranging from the regulation of gene expression to stress response.
29460617	4	58	theme	various	662:668	arg1	models					701:706	various Alzheimer's disease (AD) mouse models	662:706	various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology	662:750	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	7	59	theme	primary	1070:1076	arg1	neurons					1082:1088	primary rat neurons	1070:1088	primary rat neurons	1070:1088	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	7	60	theme	methods	1031:1037	arg1	range					1022:1026	a range	1020:1026	a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain	1020:1108	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
29460617	1	61	theme	O-linked	160:167	arg1	residues					189:196	O-linked N-acetylglucosamine residues	160:196	O-linked N-acetylglucosamine residues (O-GlcNAc)	160:207	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	1	61	theme	O-linked	160:167	arg1	O-GlcNAc					199:206	O-GlcNAc	199:206	O-GlcNAc	199:206	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	8	62	theme	tauopathy	1357:1365	arg1	model					1373:1377	the JNPL3 tauopathy mouse model	1347:1377	the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1347:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	10	63	theme	AD	1722:1723	arg1	progression					1707:1717	the progression	1703:1717	the progression of AD and other neurodegenerative diseases	1703:1760	Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases.
29460617	10	64	theme	neurodegenerative	1735:1751	arg1	diseases					1753:1760	other neurodegenerative diseases	1729:1760	other neurodegenerative diseases	1729:1760	Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases.
29460617	1	65	theme	N-acetylglucosamine	169:187	arg1	residues					189:196	O-linked N-acetylglucosamine residues	160:196	O-linked N-acetylglucosamine residues (O-GlcNAc)	160:207	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	1	65	theme	N-acetylglucosamine	169:187	arg1	O-GlcNAc					199:206	O-GlcNAc	199:206	O-GlcNAc	199:206	The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain.
29460617	4	66	theme	mouse	695:699	arg1	models					701:706	various Alzheimer's disease (AD) mouse models	662:706	various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology	662:750	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	11	67	theme	targeted	1797:1804	arg1	strategies					1806:1815	more targeted strategies	1792:1815	more targeted strategies to stimulate autophagy in an mTOR-independent manner	1792:1868	Moreover, these data suggest more targeted strategies to stimulate autophagy in an mTOR-independent manner may be found within the O-GlcNAc pathway.
29460617	10	68	theme	therapeutic	1668:1678	arg1	strategy					1680:1687	a feasible therapeutic strategy	1657:1687	a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases	1657:1760	Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases.
29460617	4	69	theme	O-GlcNAcase	564:574	arg1	inhibition					550:559	Pharmacological inhibition	534:559	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc,	534:620	Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer's disease (AD) mouse models manifesting either tau or amyloid pathology.
29460617	8	70	theme	OGA	1237:1239	arg1	inhibition					1241:1250	OGA inhibition	1237:1250	OGA inhibition	1237:1250	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	10	71	theme	OGA	1636:1638	arg1	inhibition					1640:1649	OGA inhibition	1636:1649	OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases	1636:1760	Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases.
29460617	8	72	theme	mouse	1367:1371	arg1	model					1373:1377	the JNPL3 tauopathy mouse model	1347:1377	the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model	1347:1412	Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model.
29460617	9	73	theme	OGA	1451:1453	arg1	inhibitors					1455:1464	OGA inhibitors	1451:1464	OGA inhibitors	1451:1464	These results strongly suggest that OGA inhibitors act within brain through a mechanism involving enhancement of autophagy, which aids the brain in combatting the accumulation of toxic protein species.
29460617	7	74	from	neurons	1082:1088	arg1	range					1022:1026	a range	1020:1026	a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain	1020:1108	Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity.
30305738	9	0	theme	overall	1843:1849	arg1	survival					1851:1858	increased overall survival	1833:1858	increased overall survival	1833:1858	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	4	1	theme	T	643:643	arg1	cells					645:649	T cells	643:649	T cells isolated from specimens collected from patients with ovarian cancer	643:717	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	3	2	theme	T	563:563	arg1	cells					565:569	T cells	563:569	T cells	563:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	3	3	from	cells	565:569	arg1	response9,10					547:558	the unfolded protein response9,10	526:558	the unfolded protein response9,10 in T cells	526:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	3	3	from	cells	565:569	arg1	arm					519:521	the IRE1α-XBP1 arm	504:521	the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function	504:637	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	2	4	theme	metabolic	294:302	arg1	signals					311:317	metabolic stress signals	294:317	metabolic stress signals	294:317	However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals.
30305738	6	5	theme	T	1279:1279	arg1	cells					1281:1285	T cells	1279:1285	T cells	1279:1285	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	10	6	theme	metabolic	1961:1969	arg1	fitness					1971:1977	metabolic fitness	1961:1977	metabolic fitness	1961:1977	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	5	7	with	patients	885:892	arg1	cancer					907:912	ovarian cancer	899:912	ovarian cancer	899:912	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	4	8	theme	XBP1	736:739	arg1	upregulation					720:731	upregulation	720:731	upregulation of XBP1	720:739	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	10	9	theme	T	2007:2007	arg1	cells					2009:2013	T cells	2007:2013	T cells	2007:2013	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	5	10	theme	N-linked	950:957	arg1	defects					981:987	N-linked protein glycosylation defects	950:987	N-linked protein glycosylation defects	950:987	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	3	11	theme	anti-tumour	618:628	arg1	function					630:637	anti-tumour function	618:637	anti-tumour function	618:637	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	8	12	theme	global	1607:1612	arg1	reprogramming					1630:1642	global transcriptional reprogramming	1607:1642	global transcriptional reprogramming	1607:1642	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	7	13	theme	human	1485:1489	arg1	cells					1493:1497	human T cells	1485:1497	human T cells exposed to ovarian cancer ascites	1485:1531	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	5	14	theme	glucose	924:930	arg1	uptake					932:937	glucose uptake	924:937	glucose uptake	924:937	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	10	15	from	fitness	1971:1977	arg1	hosts					2025:2029	cancer hosts	2018:2029	cancer hosts	2018:2029	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	8	16	theme	improved	1648:1655	arg1	capacity					1666:1673	improved effector capacity	1648:1673	improved effector capacity	1648:1673	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	7	17	theme	ovarian	1510:1516	arg1	ascites					1525:1531	ovarian cancer ascites	1510:1531	ovarian cancer ascites	1510:1531	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	4	18	theme	cells	789:793	arg1	infiltration					771:782	decreased infiltration	761:782	decreased infiltration of T cells into tumours	761:806	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	3	19	theme	mitochondrial	588:600	arg1	respiration					602:612	their mitochondrial respiration	582:612	their mitochondrial respiration	582:612	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	1	20	theme	hostile	133:139	arg1	microenvironments					141:157	hostile microenvironments	133:157	hostile microenvironments that perturb T cell metabolism and effector function1-4	133:213	Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4.
30305738	3	21	theme	ovarian	340:346	arg1	malignancy					369:378	ovarian cancer-an aggressive malignancy	340:378	ovarian cancer-an aggressive malignancy that is refractory to standard treatments	340:420	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	10	22	dep	fitness	1971:1977	arg1	the					1957:1959	the	1957:1959	the	1957:1959	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	4	23	attach	isolated	651:658	arg1	specimens					665:673	specimens	665:673	specimens collected from patients with ovarian cancer	665:717	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	4	23	attach	isolated	651:658	arg2	cells					645:649	T cells	643:649	T cells isolated from specimens collected from patients with ovarian cancer	643:717	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	9	24	theme	ovarian	1704:1710	arg1	cancer					1712:1717	ovarian cancer	1704:1717	ovarian cancer	1704:1717	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	4	25	theme	decreased	761:769	arg1	infiltration					771:782	decreased infiltration	761:782	decreased infiltration of T cells into tumours	761:806	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	0	26	theme	mitochondrial	68:80	arg1	activity					82:89	mitochondrial activity	68:89	mitochondrial activity	68:89	IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity.
30305738	5	27	from	defects	981:987	arg1	cells					994:998	T cells	992:998	T cells	992:998	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	1	28	theme	T	172:172	arg1	cell					174:177	T cell metabolism and effector function1-4	172:213	cell	174:177	Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4.
30305738	4	29	theme	IFNG	825:828	arg1	expression					835:844	reduced IFNG mRNA expression	817:844	reduced IFNG mRNA expression	817:844	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	9	30	theme	superior	1768:1775	arg1	immunity					1789:1796	superior anti-tumour immunity	1768:1796	superior anti-tumour immunity	1768:1796	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	5	31	theme	mitochondrial	1055:1067	arg1	activity					1069:1076	mitochondrial activity	1055:1076	mitochondrial activity	1055:1076	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	3	32	theme	aggressive	358:367	arg1	malignancy					369:378	ovarian cancer-an aggressive malignancy	340:378	ovarian cancer-an aggressive malignancy that is refractory to standard treatments	340:420	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	5	33	link	N-linked	950:957	arg1	defects					981:987	N-linked protein glycosylation defects	950:987	N-linked protein glycosylation defects	950:987	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	3	34	theme	standard	402:409	arg1	treatments					411:420	standard treatments	402:420	standard treatments	402:420	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	0	35	from	function	27:34	arg1	cancer					47:52	ovarian cancer	39:52	ovarian cancer	39:52	IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity.
30305738	3	36	theme	reticulum	473:481	arg1	stress					483:488	endoplasmic reticulum stress	461:488	endoplasmic reticulum stress	461:488	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	5	37	theme	IRE1α-XBP1	1017:1026	arg1	activation					1028:1037	IRE1α-XBP1 activation	1017:1037	IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production	1017:1096	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	6	38	theme	glutamine	1161:1169	arg1	carriers					1171:1178	glutamine carriers	1161:1178	glutamine carriers	1161:1178	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	8	39	theme	T	1549:1549	arg1	cells					1551:1555	XBP1-deficient T cells	1534:1555	XBP1-deficient T cells in the metastatic ovarian cancer milieu	1534:1595	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	0	40	theme	T	20:20	arg1	function					27:34	T cell function	20:34	T cell function in ovarian cancer	20:52	IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity.
30305738	1	41	theme	immune	106:111	arg1	control					113:119	immune control	106:119	immune control	106:119	Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4.
30305738	10	42	theme	reticulum	1885:1893	arg1	stress					1895:1900	endoplasmic reticulum stress	1873:1900	endoplasmic reticulum stress	1873:1900	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	5	43	theme	Malignant	847:855	arg1	fluid					865:869	Malignant ascites fluid	847:869	Malignant ascites fluid obtained from patients with ovarian cancer	847:912	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	1	44	dep	cell	174:177	arg1	metabolism					179:188	metabolism	179:188	metabolism	179:188	Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4.
30305738	1	44	dep	cell	174:177	arg1	function1-4					203:213	function1-4	203:213	function1-4	203:213	Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4.
30305738	3	45	theme	protein	539:545	arg1	response9,10					547:558	the unfolded protein response9,10	526:558	the unfolded protein response9,10 in T cells	526:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	0	46	theme	ovarian	39:45	arg1	cancer					47:52	ovarian cancer	39:52	ovarian cancer	39:52	IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity.
30305738	9	47	theme	delayed	1799:1805	arg1	progression					1817:1827	delayed malignant progression	1799:1827	delayed malignant progression	1799:1827	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	7	48	theme	glutamine	1424:1432	arg1	transporters					1434:1445	glutamine transporters	1424:1445	glutamine transporters	1424:1445	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	2	49	theme	intra-tumoral	248:260	arg1	cells					264:268	intra-tumoral T cells	248:268	intra-tumoral T cells	248:268	However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals.
30305738	8	50	theme	cancer	1583:1588	arg1	milieu					1590:1595	the metastatic ovarian cancer milieu	1560:1595	the metastatic ovarian cancer milieu	1560:1595	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	10	51	theme	IRE1α-XBP1	1915:1924	arg1	signalling					1926:1935	IRE1α-XBP1 signalling	1915:1935	IRE1α-XBP1 signalling	1915:1935	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	10	52	theme	endoplasmic	1873:1883	arg1	reticulum					1885:1893	endoplasmic reticulum	1873:1893	endoplasmic reticulum stress	1873:1900	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	6	53	theme	glutamine	1211:1219	arg1	influx					1201:1206	the influx	1197:1206	the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions	1197:1319	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	6	53	theme	glutamine	1211:1219	arg1	necessary					1229:1237	necessary	1229:1237	necessary	1229:1237	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	4	54	with	patients	690:697	arg1	cancer					712:717	ovarian cancer	704:717	ovarian cancer	704:717	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	9	55	theme	increased	1833:1841	arg1	survival					1851:1858	increased overall survival	1833:1858	increased overall survival	1833:1858	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	7	56	theme	IRE1α-XBP1	1375:1384	arg1	activation					1386:1395	IRE1α-XBP1 activation	1375:1395	IRE1α-XBP1 activation	1375:1395	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	8	57	theme	metastatic	1564:1573	arg1	cancer					1583:1588	the metastatic ovarian cancer	1560:1588	the metastatic ovarian cancer milieu	1560:1595	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	2	58	theme	stress	304:309	arg1	signals					311:317	metabolic stress signals	294:317	metabolic stress signals	294:317	However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals.
30305738	10	59	theme	cells	2009:2013	arg1	fitness					1971:1977	metabolic fitness	1961:1977	metabolic fitness	1961:1977	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	10	59	theme	cells	2009:2013	arg1	capacity					1995:2002	anti-tumour capacity	1983:2002	anti-tumour capacity	1983:2002	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	10	60	theme	anti-tumour	1983:1993	arg1	capacity					1995:2002	anti-tumour capacity	1983:2002	anti-tumour capacity	1983:2002	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	7	61	theme	protein	1341:1347	arg1	glycosylation					1349:1361	N-linked protein glycosylation	1332:1361	N-linked protein glycosylation	1332:1361	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	7	62	link	N-linked	1332:1339	arg1	glycosylation					1349:1361	N-linked protein glycosylation	1332:1361	N-linked protein glycosylation	1332:1361	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	8	63	from	cells	1551:1555	arg1	milieu					1590:1595	the metastatic ovarian cancer milieu	1560:1595	the metastatic ovarian cancer milieu	1560:1595	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	6	64	theme	mitochondrial	1250:1262	arg1	respiration					1264:1274	mitochondrial respiration	1250:1274	mitochondrial respiration	1250:1274	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	3	65	from	response9,10	547:558	arg1	cells					565:569	T cells	563:569	T cells	563:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	5	66	theme	ovarian	899:905	arg1	cancer					907:912	ovarian cancer	899:912	ovarian cancer	899:912	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	8	67	theme	transcriptional	1614:1628	arg1	reprogramming					1630:1642	global transcriptional reprogramming	1607:1642	global transcriptional reprogramming	1607:1642	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	4	68	theme	ovarian	704:710	arg1	cancer					712:717	ovarian cancer	704:717	ovarian cancer	704:717	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	10	69	theme	cancer	2018:2023	arg1	hosts					2025:2029	cancer hosts	2018:2029	cancer hosts	2018:2029	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	5	70	theme	T	992:992	arg1	cells					994:998	T cells	992:998	T cells	992:998	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	8	71	theme	effector	1657:1664	arg1	capacity					1666:1673	improved effector capacity	1648:1673	improved effector capacity	1648:1673	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	9	72	theme	malignant	1807:1815	arg1	progression					1817:1827	delayed malignant progression	1799:1827	delayed malignant progression	1799:1827	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	6	73	theme	XBP1	1129:1132	arg1	induction					1116:1124	induction	1116:1124	induction of XBP1	1116:1132	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	7	74	theme	cancer	1518:1523	arg1	ascites					1525:1531	ovarian cancer ascites	1510:1531	ovarian cancer ascites	1510:1531	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	4	75	theme	T	787:787	arg1	cells					789:793	T cells	787:793	T cells	787:793	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	2	76	theme	T	262:262	arg1	cells					264:268	intra-tumoral T cells	248:268	intra-tumoral T cells	248:268	However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals.
30305738	5	77	theme	protein	959:965	arg1	defects					981:987	N-linked protein glycosylation defects	950:987	N-linked protein glycosylation defects	950:987	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	6	78	theme	glucose-deprived	1293:1308	arg1	conditions					1310:1319	glucose-deprived conditions	1293:1319	glucose-deprived conditions	1293:1319	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	7	79	theme	N-linked	1332:1339	arg1	glycosylation					1349:1361	N-linked protein glycosylation	1332:1361	N-linked protein glycosylation	1332:1361	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	10	80	from	capacity	1995:2002	arg1	hosts					2025:2029	cancer hosts	2018:2029	cancer hosts	2018:2029	Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.
30305738	4	81	theme	reduced	817:823	arg1	expression					835:844	reduced IFNG mRNA expression	817:844	reduced IFNG mRNA expression	817:844	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	7	82	theme	T	1491:1491	arg1	cells					1493:1497	human T cells	1485:1497	human T cells exposed to ovarian cancer ascites	1485:1531	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	4	83	theme	mRNA	830:833	arg1	expression					835:844	reduced IFNG mRNA expression	817:844	reduced IFNG mRNA expression	817:844	In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression.
30305738	9	84	theme	T	1748:1748	arg1	cells					1750:1754	T cells	1748:1754	T cells	1748:1754	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	6	85	theme	carriers	1171:1178	arg1	abundance					1148:1156	the abundance	1144:1156	the abundance of glutamine carriers	1144:1178	Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions.
30305738	0	86	theme	cell	22:25	arg1	function					27:34	T cell function	20:34	T cell function in ovarian cancer	20:52	IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity.
30305738	7	87	theme	mitochondrial	1456:1468	arg1	respiration					1470:1480	mitochondrial respiration	1456:1480	mitochondrial respiration	1456:1480	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	8	88	theme	XBP1-deficient	1534:1547	arg1	cells					1551:1555	XBP1-deficient T cells	1534:1555	XBP1-deficient T cells in the metastatic ovarian cancer milieu	1534:1595	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	9	89	theme	anti-tumour	1777:1787	arg1	immunity					1789:1796	superior anti-tumour immunity	1768:1796	superior anti-tumour immunity	1768:1796	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	7	90	theme	transporters	1434:1445	arg1	expression					1410:1419	enforcing expression	1400:1419	enforcing expression of glutamine transporters	1400:1445	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	3	91	theme	endoplasmic	461:471	arg1	reticulum					473:481	endoplasmic reticulum	461:481	endoplasmic reticulum stress	461:488	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	3	92	theme	IRE1α-XBP1	508:517	arg1	response9,10					547:558	the unfolded protein response9,10	526:558	the unfolded protein response9,10 in T cells	526:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	3	92	theme	IRE1α-XBP1	508:517	arg1	arm					519:521	the IRE1α-XBP1 arm	504:521	the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function	504:637	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	5	93	theme	ascites	857:863	arg1	fluid					865:869	Malignant ascites fluid	847:869	Malignant ascites fluid obtained from patients with ovarian cancer	847:912	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	3	94	from	arm	519:521	arg1	cells					565:569	T cells	563:569	T cells	563:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	3	95	theme	response9,10	547:558	arg1	response9,10					547:558	the unfolded protein response9,10	526:558	the unfolded protein response9,10 in T cells	526:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	3	95	theme	response9,10	547:558	arg1	arm					519:521	the IRE1α-XBP1 arm	504:521	the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function	504:637	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	5	96	theme	IFNγ	1082:1085	arg1	production					1087:1096	IFNγ production	1082:1096	IFNγ production	1082:1096	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
30305738	7	97	theme	enforcing	1400:1408	arg1	expression					1410:1419	enforcing expression	1400:1419	enforcing expression of glutamine transporters	1400:1445	Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites.
30305738	9	98	contain	bear	1699:1702	arg1	mice					1689:1692	mice	1689:1692	mice that bear ovarian cancer and lack XBP1 selectively in T cells	1689:1754	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	9	98	contain	bear	1699:1702	arg2	cancer					1712:1717	ovarian cancer	1704:1717	ovarian cancer	1704:1717	Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival.
30305738	8	99	theme	ovarian	1575:1581	arg1	cancer					1583:1588	the metastatic ovarian cancer	1560:1588	the metastatic ovarian cancer milieu	1560:1595	XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity.
30305738	3	100	theme	unfolded	530:537	arg1	response9,10					547:558	the unfolded protein response9,10	526:558	the unfolded protein response9,10 in T cells	526:569	Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function.
30305738	5	101	theme	glycosylation	967:979	arg1	defects					981:987	N-linked protein glycosylation defects	950:987	N-linked protein glycosylation defects	950:987	Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production.
31810853	2	0	from	worldwide	174:182	arg1	animals					187:193	animals	187:193	animals	187:193	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	2	0	from	worldwide	174:182	arg1	humans					199:204	humans	199:204	humans	199:204	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	5	1	theme	transmembrane	755:767	arg1	domain					769:774	transmembrane domain	755:774	transmembrane domain	755:774	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	5	2	theme	bioinformatics	601:614	arg1	analyses					616:623	several bioinformatics analyses	593:623	several bioinformatics analyses	593:623	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	8	3	theme	protein	1112:1118	arg1	S5					1120:1121	ribosomal protein S5	1102:1121	ribosomal protein S5	1102:1121	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	4	theme	ribosomal	1102:1110	arg1	S5					1120:1121	ribosomal protein S5	1102:1121	ribosomal protein S5	1102:1121	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	4	5	dep	encoded	436:442	arg1	genome					429:434	genome	429:434	genome	429:434	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	6	6	theme	structural	821:830	arg1	sites					861:865	structural, B cell and MHC-I/II epitope sites	821:865	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	7	7	theme	probable	1058:1065	arg1	19					1037:1038	19	1037:1038	19	1037:1038	Of the 28 apicoplast proteins, 19 were predicted as probable antigen.
31810853	7	7	theme	probable	1058:1065	arg1	antigen					1067:1073	probable antigen	1058:1073	probable antigen	1058:1073	Of the 28 apicoplast proteins, 19 were predicted as probable antigen.
31810853	9	8	theme	percentile	1407:1416	arg1	value					1423:1427	low IC50 and percentile rank value	1394:1427	value	1423:1427	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	9	contain	have	1389:1392	arg1	epitopes					1374:1381	epitopes	1374:1381	epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation	1374:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	9	contain	have	1389:1392	arg2	IC50					1398:1401	low IC50 and percentile rank value	1394:1427	IC50	1398:1401	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	9	contain	have	1389:1392	arg2	value					1423:1427	low IC50 and percentile rank value	1394:1427	value	1423:1427	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	3	10	theme	endosymbiotic	331:343	arg1	event					345:349	a secondary endosymbiotic event	319:349	a secondary endosymbiotic event	319:349	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	4	11	dep	in	479:480	arg1	silico					482:487	silico	482:487	silico	482:487	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	10	12	theme	T.	1741:1742	arg1	proteins					1729:1736	apicoplast-derived proteins	1710:1736	apicoplast-derived proteins of T. gondii	1710:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	10	13	theme	other	1690:1694	arg1	properties					1696:1705	the antigenic potential and other properties	1662:1705	the antigenic potential and other properties of apicoplast-derived proteins of T. gondii	1662:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	9	14	theme	MHC-I/II	1476:1483	arg1	acetylation					1563:1573	acetylation	1563:1573	acetylation	1563:1573	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	14	theme	MHC-I/II	1476:1483	arg1	glycosylation					1548:1560	N-linked glycosylation	1539:1560	N-linked glycosylation	1539:1560	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	14	theme	MHC-I/II	1476:1483	arg1	alleles					1485:1491	MHC-I/II alleles	1476:1491	MHC-I/II alleles	1476:1491	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	14	theme	MHC-I/II	1476:1483	arg1	phosphorylation					1579:1593	phosphorylation	1579:1593	phosphorylation	1579:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	6	15	theme	antigenicity	986:997	arg1	value					999:1003	a high antigenicity value	979:1003	a high antigenicity value	979:1003	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	2	16	theme	parasites	150:158	arg1	gondii					98:103	Toxoplasma gondii	87:103	Toxoplasma gondii	87:103	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	2	16	theme	parasites	150:158	arg1	one					106:108	one	106:108	one	106:108	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	2	16	theme	parasites	150:158	arg1	parasites					150:158	the extensively studied Apicomplexan parasites	113:158	the extensively studied Apicomplexan parasites	113:158	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	5	17	theme	antigenic	561:569	arg1	probability					571:581	antigenic probability	561:581	antigenic probability	561:581	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	8	18	contain	have	1153:1156	arg1	S2					1132:1133	S2	1132:1133	S2	1132:1133	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	18	contain	have	1153:1156	arg1	L11					1124:1126	L11	1124:1126	L11	1124:1126	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	18	contain	have	1153:1156	arg2	peptide					1165:1171	signal peptide	1158:1171	signal peptide	1158:1171	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	18	contain	have	1153:1156	arg1	S5					1120:1121	ribosomal protein S5	1102:1121	ribosomal protein S5	1102:1121	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	10	19	theme	first	1642:1646	arg1	this					1630:1633	this	1630:1633	this	1630:1633	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	10	19	theme	first	1642:1646	arg1	study					1648:1652	the first study	1638:1652	the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii	1638:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	6	20	theme	high	981:984	arg1	value					999:1003	a high antigenicity value	979:1003	a high antigenicity value	979:1003	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	4	21	theme	proteins	444:451	arg1	potential					405:413	the antigenic potential	391:413	the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii	391:471	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	0	22	contain	have	41:44	arg2	potential					56:64	antigenic potential	46:64	antigenic potential	46:64	Do Toxoplasma gondii apicoplast proteins have antigenic potential?
31810853	0	22	contain	have	41:44	arg1	proteins					32:39	Toxoplasma gondii apicoplast proteins	3:39	Toxoplasma gondii apicoplast proteins	3:39	Do Toxoplasma gondii apicoplast proteins have antigenic potential?
31810853	1	23	theme	in	70:71	arg1	study					80:84	An in silico study	67:84	An in silico study.	67:85	An in silico study.
31810853	3	24	theme	secondary	321:329	arg1	event					345:349	a secondary endosymbiotic event	319:349	a secondary endosymbiotic event	319:349	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	2	25	theme	studied	129:135	arg1	parasites					150:158	the extensively studied Apicomplexan parasites	113:158	the extensively studied Apicomplexan parasites	113:158	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	8	26	contain	have	1229:1232	arg1	L36					1199:1201	ribosomal protein L36	1181:1201	ribosomal protein L36	1181:1201	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	26	contain	have	1229:1232	arg1	S17					1207:1209	S17	1207:1209	S17	1207:1209	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	26	contain	have	1229:1232	arg2	P < 0.05					1275:1282	P < 0.05	1275:1282	P < 0.05	1275:1282	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	26	contain	have	1229:1232	arg2	value					1268:1272	a significantly high antigenicity value	1234:1272	a significantly high antigenicity value (P < 0.05)	1234:1283	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	6	27	theme	further	783:789	arg1	analyses					802:809	further prediction analyses	783:809	further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	783:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	6	27	theme	further	783:789	arg1	modifications					897:909	post-translational modifications	878:909	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	6	27	theme	further	783:789	arg1	sites					861:865	structural, B cell and MHC-I/II epitope sites	821:865	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	9	28	theme	rank	1418:1421	arg1	value					1423:1427	low IC50 and percentile rank value	1394:1427	value	1423:1427	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	8	29	theme	high	1250:1253	arg1	P < 0.05					1275:1282	P < 0.05	1275:1282	P < 0.05	1275:1282	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	29	theme	high	1250:1253	arg1	value					1268:1272	a significantly high antigenicity value	1234:1272	a significantly high antigenicity value (P < 0.05)	1234:1283	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	0	30	theme	Toxoplasma	3:12	arg1	proteins					32:39	Toxoplasma gondii apicoplast proteins	3:39	Toxoplasma gondii apicoplast proteins	3:39	Do Toxoplasma gondii apicoplast proteins have antigenic potential?
31810853	10	31	theme	potential	1676:1684	arg1	properties					1696:1705	the antigenic potential and other properties	1662:1705	the antigenic potential and other properties of apicoplast-derived proteins of T. gondii	1662:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	3	32	theme	nuclear	222:228	arg1	genome					230:235	its nuclear genome	218:235	its nuclear genome	218:235	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	9	33	contain	have	1360:1363	arg1	S17					1338:1340	S17	1338:1340	S17	1338:1340	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	33	contain	have	1360:1363	arg1	L11					1321:1323	L11	1321:1323	L11	1321:1323	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	33	contain	have	1360:1363	arg1	S2					1326:1327	S2	1326:1327	S2	1326:1327	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	33	contain	have	1360:1363	arg1	S5					1317:1318	ribosomal protein S5	1299:1318	ribosomal protein S5	1299:1318	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	33	contain	have	1360:1363	arg2	lot					1367:1369	a lot	1365:1369	a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation	1365:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	33	contain	have	1360:1363	arg1	L36					1330:1332	L36	1330:1332	L36	1330:1332	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	33	contain	have	1360:1363	arg2	epitopes					1374:1381	epitopes	1374:1381	epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation	1374:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	10	34	theme	proteins	1729:1736	arg1	properties					1696:1705	the antigenic potential and other properties	1662:1705	the antigenic potential and other properties of apicoplast-derived proteins of T. gondii	1662:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	2	35	theme	Apicomplexan	137:148	arg1	parasites					150:158	the extensively studied Apicomplexan parasites	113:158	the extensively studied Apicomplexan parasites	113:158	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	9	36	theme	epitopes	1374:1381	arg1	epitopes					1374:1381	epitopes	1374:1381	epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation	1374:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	36	theme	epitopes	1374:1381	arg1	lot					1367:1369	a lot	1365:1369	a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation	1365:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	8	37	theme	signal	1158:1163	arg1	peptide					1165:1171	signal peptide	1158:1171	signal peptide	1158:1171	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	9	38	theme	ribosomal	1299:1307	arg1	S5					1317:1318	ribosomal protein S5	1299:1318	ribosomal protein S5	1299:1318	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	5	39	theme	several	593:599	arg1	analyses					616:623	several bioinformatics analyses	593:623	several bioinformatics analyses	593:623	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	10	40	theme	apicoplast-derived	1710:1727	arg1	proteins					1729:1736	apicoplast-derived proteins	1710:1736	apicoplast-derived proteins of T. gondii	1710:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	3	41	contain	contains	248:255	arg1	gondii					241:246	T. gondii	238:246	T. gondii	238:246	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	3	41	contain	contains	248:255	arg2	genome					271:276	an apicoplast genome	257:276	an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event	257:349	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	0	42	theme	apicoplast	21:30	arg1	proteins					32:39	Toxoplasma gondii apicoplast proteins	3:39	Toxoplasma gondii apicoplast proteins	3:39	Do Toxoplasma gondii apicoplast proteins have antigenic potential?
31810853	9	43	theme	protein	1309:1315	arg1	S5					1317:1318	ribosomal protein S5	1299:1318	ribosomal protein S5	1299:1318	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	5	44	theme	apicoplast	666:675	arg1	proteins					677:684	all predicted antigenic apicoplast proteins	642:684	all predicted antigenic apicoplast proteins	642:684	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	6	45	theme	prediction	791:800	arg1	analyses					802:809	further prediction analyses	783:809	further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	783:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	6	45	theme	prediction	791:800	arg1	modifications					897:909	post-translational modifications	878:909	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	6	45	theme	prediction	791:800	arg1	sites					861:865	structural, B cell and MHC-I/II epitope sites	821:865	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	9	46	theme	post-translational	1498:1515	arg1	acetylation					1563:1573	acetylation	1563:1573	acetylation	1563:1573	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	46	theme	post-translational	1498:1515	arg1	glycosylation					1548:1560	N-linked glycosylation	1539:1560	N-linked glycosylation	1539:1560	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	46	theme	post-translational	1498:1515	arg1	phosphorylation					1579:1593	phosphorylation	1579:1593	phosphorylation	1579:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	46	theme	post-translational	1498:1515	arg1	modifications					1517:1529	post-translational modifications	1498:1529	post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation	1498:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	0	47	theme	gondii	14:19	arg1	proteins					32:39	Toxoplasma gondii apicoplast proteins	3:39	Toxoplasma gondii apicoplast proteins	3:39	Do Toxoplasma gondii apicoplast proteins have antigenic potential?
31810853	3	48	theme	apicoplast	260:269	arg1	genome					271:276	an apicoplast genome	257:276	an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event	257:349	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	4	49	theme	apicoplast	418:427	arg1	n:28					454:457	n:28	454:457	n:28	454:457	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	4	49	theme	apicoplast	418:427	arg1	proteins					444:451	apicoplast genome encoded proteins	418:451	apicoplast genome encoded proteins (n:28) of T. gondii	418:471	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	9	50	theme	low	1394:1396	arg1	IC50					1398:1401	low IC50 and percentile rank value	1394:1427	IC50	1398:1401	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	9	51	link	N-linked	1539:1546	arg1	glycosylation					1548:1560	N-linked glycosylation	1539:1560	N-linked glycosylation	1539:1560	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	6	52	theme	signal	961:966	arg1	peptide					968:974	a signal peptide	959:974	a signal peptide	959:974	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	2	53	theme	prevalent	164:172	arg1	worldwide					174:182	prevalent worldwide	164:182	prevalent worldwide in animals and humans	164:204	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	8	54	theme	antigenicity	1255:1266	arg1	P < 0.05					1275:1282	P < 0.05	1275:1282	P < 0.05	1275:1282	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	54	theme	antigenicity	1255:1266	arg1	value					1268:1272	a significantly high antigenicity value	1234:1272	a significantly high antigenicity value (P < 0.05)	1234:1283	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	55	theme	protein	1191:1197	arg1	L36					1199:1201	ribosomal protein L36	1181:1201	ribosomal protein L36	1181:1201	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	8	56	theme	antigenic	1082:1090	arg1	proteins					1092:1099	antigenic proteins	1082:1099	antigenic proteins	1082:1099	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	4	57	theme	encoded	436:442	arg1	n:28					454:457	n:28	454:457	n:28	454:457	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	4	57	theme	encoded	436:442	arg1	proteins					444:451	apicoplast genome encoded proteins	418:451	apicoplast genome encoded proteins (n:28) of T. gondii	418:471	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	8	58	theme	ribosomal	1181:1189	arg1	L36					1199:1201	ribosomal protein L36	1181:1201	ribosomal protein L36	1181:1201	Among antigenic proteins, ribosomal protein S5, L11 and S2 were predicted to have signal peptide whereas ribosomal protein L36 and S17 were predicted to have a significantly high antigenicity value (P < 0.05).
31810853	5	59	theme	subcellular	726:736	arg1	localization					738:749	subcellular localization	726:749	subcellular localization	726:749	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	2	60	theme	Toxoplasma	87:96	arg1	parasites					150:158	the extensively studied Apicomplexan parasites	113:158	the extensively studied Apicomplexan parasites	113:158	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	2	60	theme	Toxoplasma	87:96	arg1	one					106:108	one	106:108	one	106:108	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	2	60	theme	Toxoplasma	87:96	arg1	gondii					98:103	Toxoplasma gondii	87:103	Toxoplasma gondii	87:103	Toxoplasma gondii, one of the extensively studied Apicomplexan parasites, is prevalent worldwide in animals and humans.
31810853	3	61	theme	35 kb	281:285	arg1	length					287:292	35 kb length	281:292	35 kb length	281:292	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	6	62	theme	MHC-I/II	844:851	arg1	epitope					853:859	MHC-I/II epitope	844:859	MHC-I/II epitope	844:859	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	9	63	theme	N-linked	1539:1546	arg1	glycosylation					1548:1560	N-linked glycosylation	1539:1560	N-linked glycosylation	1539:1560	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	7	64	theme	apicoplast	1016:1025	arg1	proteins					1027:1034	the 28 apicoplast proteins	1009:1034	the 28 apicoplast proteins	1009:1034	Of the 28 apicoplast proteins, 19 were predicted as probable antigen.
31810853	1	65	dep	in	70:71	arg1	silico					73:78	silico	73:78	silico	73:78	An in silico study.
31810853	0	66	theme	antigenic	46:54	arg1	potential					56:64	antigenic potential	46:64	antigenic potential	46:64	Do Toxoplasma gondii apicoplast proteins have antigenic potential?
31810853	6	67	theme	antigenic	930:938	arg1	proteins					940:947	antigenic proteins	930:947	antigenic proteins that have a signal peptide or a high antigenicity value	930:1003	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	5	68	theme	physico-chemical	697:712	arg1	parameters					714:723	physico-chemical parameters	697:723	physico-chemical parameters	697:723	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	6	69	theme	epitope	853:859	arg1	sites					861:865	structural, B cell and MHC-I/II epitope sites	821:865	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	10	70	link	apicoplast-derived	1710:1727	arg1	proteins					1729:1736	apicoplast-derived proteins	1710:1736	apicoplast-derived proteins of T. gondii	1710:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	5	71	theme	predicted	646:654	arg1	proteins					677:684	all predicted antigenic apicoplast proteins	642:684	all predicted antigenic apicoplast proteins	642:684	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	6	72	theme	cell	835:838	arg1	sites					861:865	structural, B cell and MHC-I/II epitope sites	821:865	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	6	73	theme	post-translational	878:895	arg1	modifications					897:909	post-translational modifications	878:909	structural, B cell and MHC-I/II epitope sites as well as post-translational modifications	821:909	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	3	74	from	genome	271:276	arg1	length					287:292	35 kb length	281:292	35 kb length	281:292	Apart from its nuclear genome, T. gondii contains an apicoplast genome in 35 kb length which is originated from a secondary endosymbiotic event.
31810853	5	75	theme	antigenic	656:664	arg1	proteins					677:684	all predicted antigenic apicoplast proteins	642:684	all predicted antigenic apicoplast proteins	642:684	For this purpose, proteins were primarily predicted to reveal antigenic probability and then, several bioinformatics analyses were applied for all predicted antigenic apicoplast proteins to analyze physico-chemical parameters, subcellular localization and transmembrane domain.
31810853	6	76	theme	B	833:833	arg1	cell					835:838	B cell	833:838	B cell	833:838	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	4	77	theme	antigenic	395:403	arg1	potential					405:413	the antigenic potential	391:413	the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii	391:471	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	6	78	contain	have	954:957	arg1	proteins					940:947	antigenic proteins	930:947	antigenic proteins that have a signal peptide or a high antigenicity value	930:1003	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	6	78	contain	have	954:957	arg2	peptide					968:974	a signal peptide	959:974	a signal peptide	959:974	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	6	78	contain	have	954:957	arg2	value					999:1003	a high antigenicity value	979:1003	a high antigenicity value	979:1003	Also, further prediction analyses including structural, B cell and MHC-I/II epitope sites as well as post-translational modifications were performed for antigenic proteins that have a signal peptide or a high antigenicity value.
31810853	10	79	theme	antigenic	1666:1674	arg1	properties					1696:1705	the antigenic potential and other properties	1662:1705	the antigenic potential and other properties of apicoplast-derived proteins of T. gondii	1662:1749	To the best of authors' knowledge this is the first study to show the antigenic potential and other properties of apicoplast-derived proteins of T. gondii.
31810853	4	80	theme	T.	463:464	arg1	n:28					454:457	n:28	454:457	n:28	454:457	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	4	80	theme	T.	463:464	arg1	proteins					444:451	apicoplast genome encoded proteins	418:451	apicoplast genome encoded proteins (n:28) of T. gondii	418:471	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31810853	9	81	theme	strong	1442:1447	arg1	binding					1449:1455	a strong binding	1440:1455	a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation	1440:1593	In addition, ribosomal protein S5, L11, S2, L36 and S17 were predicted to have a lot of epitopes which have low IC50 and percentile rank value indicating a strong binding among epitopes and MHC-I/II alleles, and post-translational modifications such as N-linked glycosylation, acetylation and phosphorylation.
31810853	4	82	theme	in	479:480	arg1	analysis					489:496	in silico analysis	479:496	in silico analysis	479:496	In this study, we aimed to investigate the antigenic potential of apicoplast genome encoded proteins (n:28) of T. gondii using in silico analysis.
31600726	6	0	theme	glycoforms	890:899	arg1	effects					875:881	the direct effects	864:881	the direct effects of FSH glycoforms on the mouse ovarian follicle	864:929	However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined.
31600726	4	1	theme	relative	549:556	arg1	abundance					558:566	The relative abundance	545:566	The relative abundance of FSH glycoforms	545:584	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	7	2	theme	FSH	1091:1093	arg1	glycoforms					1095:1104	purified recombinant FSH glycoforms	1070:1104	purified recombinant FSH glycoforms	1070:1104	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	8	3	theme	follicles	1334:1342	arg1	Treatment					1321:1329	Treatment	1321:1329	Treatment of follicles with 100 ng/mL of each glycoform	1321:1375	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	7	4	theme	purified	1070:1077	arg1	glycoforms					1095:1104	purified recombinant FSH glycoforms	1070:1104	purified recombinant FSH glycoforms	1070:1104	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	2	5	theme	FSHβ	287:290	arg1	subunit					292:298	the FSHβ subunit	283:298	the FSHβ subunit	283:298	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	4	6	from	FSH21/18	654:661	arg1	women					674:678	younger women	666:678	younger women	666:678	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	4	6	from	FSH21/18	654:661	arg1	women					698:702	older women	692:702	older women	692:702	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	6	7	theme	direct	868:873	arg1	effects					875:881	the direct effects	864:881	the direct effects of FSH glycoforms on the mouse ovarian follicle	864:929	However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined.
31600726	5	8	dep	in	759:760	arg1	vivo					762:765	vivo	762:765	vivo	762:765	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	4	9	theme	reproductive	608:619	arg1	age					621:623	advanced reproductive age	599:623	advanced reproductive age	599:623	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	7	10	dep	20-	1053:1055	arg1	glycoforms					1095:1104	purified recombinant FSH glycoforms	1070:1104	purified recombinant FSH glycoforms	1070:1104	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	3	11	from	subunit	352:358	arg1	number					320:325	the number	316:325	the number of N-glycans on the FSHβ subunit	316:358	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	6	12	theme	ovarian	914:920	arg1	follicle					922:929	the mouse ovarian follicle	904:929	the mouse ovarian follicle	904:929	However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined.
31600726	5	13	dep	in	714:715	arg1	vitro					717:721	vitro	717:721	vitro	717:721	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	8	14	theme	FSH-responsive	1422:1435	arg1	genes					1437:1441	FSH-responsive genes	1422:1441	FSH-responsive genes	1422:1441	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	7	15	theme	pre-pubertal	1013:1024	arg1	mice					1026:1029	pre-pubertal mice	1013:1029	pre-pubertal mice	1013:1029	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	3	16	from	number	320:325	arg1	subunit					352:358	the FSHβ subunit	343:358	the FSHβ subunit	343:358	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	8	17	with	Treatment	1321:1329	arg1	ng/mL					1353:1357	100 ng/mL	1349:1357	100 ng/mL of each glycoform	1349:1375	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	3	18	from	N-glycans	330:338	arg1	subunit					352:358	the FSHβ subunit	343:358	the FSHβ subunit	343:358	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	2	19	theme	Asn24	265:269	arg1	residues					271:278	the Asn7 and Asn24 residues	252:278	the Asn7 and Asn24 residues on the FSHβ subunit	252:298	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	3	20	theme	N-glycans	330:338	arg1	number					320:325	the number	316:325	the number of N-glycans on the FSHβ subunit	316:358	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	7	21	theme	ng/mL	1309:1313	arg1	dose					1315:1318	the 100 ng/mL dose	1301:1318	the 100 ng/mL dose	1301:1318	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	4	22	theme	younger	666:672	arg1	women					674:678	younger women	666:678	younger women	666:678	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	0	23	theme	ovarian	60:66	arg1	follicles					68:76	mouse preantral ovarian follicles	44:76	mouse preantral ovarian follicles	44:76	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	2	24	theme	Asn7	256:259	arg1	residues					271:278	the Asn7 and Asn24 residues	252:278	the Asn7 and Asn24 residues on the FSHβ subunit	252:298	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	1	25	theme	hormone	156:162	arg1	levels					170:175	follicle-stimulating hormone (FSH) levels	135:175	follicle-stimulating hormone (FSH) levels during peri-menopause	135:197	Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause.
31600726	5	26	theme	cell	744:747	arg1	lines					749:753	granulosa cell lines	734:753	granulosa cell lines	734:753	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	5	27	from	studies	723:729	arg1	lines					749:753	granulosa cell lines	734:753	granulosa cell lines	734:753	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	5	27	from	studies	723:729	arg1	studies					767:773	in vivo studies	759:773	in vivo studies using Fshb-null mice	759:794	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	7	28	theme	substrates	1157:1166	arg1	Analysis					1126:1133	18-20 h. Analysis	1117:1133	18-20 h. Analysis of phosphorylated PKA substrates	1117:1166	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	3	29	gly	hypo-glycosylated	391:407	arg1	glycoforms					379:388	distinct glycoforms	370:388	distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24)	370:542	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	9	30	from	bioactive	1560:1568	arg1	follicles					1589:1597	isolated murine follicles	1573:1597	isolated murine follicles	1573:1597	Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.
31600726	2	31	attach	attached	240:247	arg2	glycans					209:215	N-linked glycans	200:215	N-linked glycans	200:215	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	2	31	attach	attached	240:247	arg1	residues					271:278	the Asn7 and Asn24 residues	252:278	the Asn7 and Asn24 residues on the FSHβ subunit	252:298	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	3	32	dep	hypo-glycosylated	391:407	arg1	glycans					420:426	glycans	420:426	glycans absent on either Asn24 or Asn7	420:457	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	32	dep	hypo-glycosylated	391:407	arg1	FSH21/18					410:417	FSH21/18	410:417	FSH21/18	410:417	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	7	33	theme	phosphorylated	1138:1151	arg1	substrates					1157:1166	phosphorylated PKA substrates	1138:1166	phosphorylated PKA substrates	1138:1166	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	1	34	from	rise	127:130	arg1	levels					170:175	follicle-stimulating hormone (FSH) levels	135:175	follicle-stimulating hormone (FSH) levels during peri-menopause	135:197	Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause.
31600726	1	35	theme	Female	79:84	arg1	aging					99:103	Female reproductive aging	79:103	Female reproductive aging	79:103	Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause.
31600726	9	36	from	follicles	1589:1597	arg1	bioactive					1560:1568	bioactive	1560:1568	bioactive	1560:1568	Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.
31600726	7	37	theme	100	1305:1307	arg1	ng/mL					1309:1313	ng/mL	1309:1313	ng/mL	1309:1313	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	0	38	from	bioactive	31:39	arg1	follicles					68:76	mouse preantral ovarian follicles	44:76	mouse preantral ovarian follicles	44:76	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	3	39	gly	fully-glycosylated	477:494	arg1	glycoforms					379:388	distinct glycoforms	370:388	distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24)	370:542	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	8	40	with	consistent	1464:1473	arg1	function					1493:1500	differential function	1480:1500	differential function	1480:1500	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	0	41	theme	Recombinant	0:10	arg1	glycoforms					16:25	Recombinant FSH glycoforms	0:25	Recombinant FSH glycoforms	0:25	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	9	42	theme	FSH	1541:1543	arg1	glycoforms					1545:1554	FSH glycoforms	1541:1554	FSH glycoforms	1541:1554	Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.
31600726	2	43	link	N-linked	200:207	arg1	glycans					209:215	N-linked glycans	200:215	N-linked glycans	200:215	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	2	44	from	residues	271:278	arg1	subunit					292:298	the FSHβ subunit	283:298	the FSHβ subunit	283:298	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	3	45	theme	hypo-glycosylated	391:407	arg1	glycoforms					379:388	distinct glycoforms	370:388	distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24)	370:542	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	8	46	theme	glycoform	1367:1375	arg1	ng/mL					1353:1357	100 ng/mL	1349:1357	100 ng/mL of each glycoform	1349:1375	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	0	47	theme	mouse	44:48	arg1	follicles					68:76	mouse preantral ovarian follicles	44:76	mouse preantral ovarian follicles	44:76	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	9	48	theme	murine	1582:1587	arg1	follicles					1589:1597	isolated murine follicles	1573:1597	isolated murine follicles	1573:1597	Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.
31600726	9	49	gly	glycoforms	1545:1554	arg1	FSH					1541:1543	FSH glycoforms	1541:1554	FSH glycoforms	1541:1554	Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.
31600726	4	50	theme	FSH	571:573	arg1	glycoforms					575:584	FSH glycoforms	571:584	FSH glycoforms	571:584	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	8	51	theme	expression	1399:1408	arg1	patterns					1410:1417	distinct expression patterns	1390:1417	distinct expression patterns of FSH-responsive genes	1390:1441	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	0	52	theme	preantral	50:58	arg1	follicles					68:76	mouse preantral ovarian follicles	44:76	mouse preantral ovarian follicles	44:76	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	7	53	theme	recombinant	1079:1089	arg1	glycoforms					1095:1104	purified recombinant FSH glycoforms	1070:1104	purified recombinant FSH glycoforms	1070:1104	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	6	54	theme	FSH	886:888	arg1	glycoforms					890:899	FSH glycoforms	886:899	FSH glycoforms	886:899	However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined.
31600726	7	55	from	bioactive	1196:1204	arg1	follicles					1209:1217	follicles	1209:1217	follicles following 1-h treatment	1209:1241	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	9	56	theme	isolated	1573:1580	arg1	follicles					1589:1597	isolated murine follicles	1573:1597	isolated murine follicles	1573:1597	Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.
31600726	7	57	from	follicles	1209:1217	arg1	bioactive					1196:1204	bioactive	1196:1204	bioactive	1196:1204	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	6	58	from	effects	875:881	arg1	follicle					922:929	the mouse ovarian follicle	904:929	the mouse ovarian follicle	904:929	However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined.
31600726	3	59	theme	present	512:518	arg1	FSH24					497:501	FSH24	497:501	FSH24	497:501	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	59	theme	present	512:518	arg1	glycans					504:510	glycans	504:510	glycans present on both Asn7 and Asn24	504:541	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	5	60	theme	differential	827:838	arg1	bioactivities					840:852	differential bioactivities	827:852	differential bioactivities	827:852	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	4	61	theme	advanced	599:606	arg1	age					621:623	advanced reproductive age	599:623	advanced reproductive age	599:623	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	3	62	theme	fully-glycosylated	477:494	arg1	glycoforms					379:388	distinct glycoforms	370:388	distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24)	370:542	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	8	63	theme	genes	1437:1441	arg1	patterns					1410:1417	distinct expression patterns	1390:1417	distinct expression patterns of FSH-responsive genes	1390:1441	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	6	64	theme	mouse	908:912	arg1	follicle					922:929	the mouse ovarian follicle	904:929	the mouse ovarian follicle	904:929	However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined.
31600726	7	65	theme	secondary	988:996	arg1	follicles					998:1006	secondary follicles	988:1006	secondary follicles	988:1006	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	4	66	theme	older	692:696	arg1	women					698:702	older women	692:702	older women	692:702	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	1	67	theme	follicle-stimulating	135:154	arg1	hormone					156:162	follicle-stimulating hormone	135:162	follicle-stimulating hormone (FSH) levels during peri-menopause	135:197	Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause.
31600726	1	67	theme	follicle-stimulating	135:154	arg1	FSH					165:167	FSH	165:167	FSH	165:167	Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause.
31600726	6	68	gly	glycoforms	890:899	arg1	FSH					886:888	FSH glycoforms	886:899	FSH glycoforms	886:899	However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined.
31600726	5	69	theme	Previous	705:712	arg1	studies					723:729	Previous in vitro studies	705:729	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice	705:794	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	5	70	theme	granulosa	734:742	arg1	lines					749:753	granulosa cell lines	734:753	granulosa cell lines	734:753	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	8	71	theme	differential	1480:1491	arg1	function					1493:1500	differential function	1480:1500	differential function	1480:1500	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	7	72	theme	PKA	1153:1155	arg1	substrates					1157:1166	phosphorylated PKA substrates	1138:1166	phosphorylated PKA substrates	1138:1166	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	4	73	gly	glycoforms	575:584	arg1	FSH					571:573	FSH glycoforms	571:584	FSH glycoforms	571:584	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	5	74	theme	in	714:715	arg1	studies					723:729	Previous in vitro studies	705:729	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice	705:794	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	3	75	theme	FSHβ	347:350	arg1	subunit					352:358	the FSHβ subunit	343:358	the FSHβ subunit	343:358	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	0	76	theme	FSH	12:14	arg1	glycoforms					16:25	Recombinant FSH glycoforms	0:25	Recombinant FSH glycoforms	0:25	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	1	77	theme	reproductive	86:97	arg1	aging					99:103	Female reproductive aging	79:103	Female reproductive aging	79:103	Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause.
31600726	3	78	theme	absent	428:433	arg1	glycans					420:426	glycans	420:426	glycans absent on either Asn24 or Asn7	420:457	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	78	theme	absent	428:433	arg1	FSH21/18					410:417	FSH21/18	410:417	FSH21/18	410:417	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	5	79	theme	Fshb-null	781:789	arg1	mice					791:794	Fshb-null mice	781:794	Fshb-null mice	781:794	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	5	80	dep	showed	796:801	arg1	elicit					820:825	elicit	820:825	showed these glycoforms elicit differential bioactivities	796:852	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	3	81	theme	distinct	370:377	arg1	glycoforms					379:388	distinct glycoforms	370:388	distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24)	370:542	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	82	attach	present	512:518	arg2	glycans					504:510	glycans	504:510	glycans present on both Asn7 and Asn24	504:541	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	82	attach	present	512:518	arg1	Asn24					537:541	Asn24	537:541	Asn24	537:541	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	82	attach	present	512:518	arg2	FSH24					497:501	FSH24	497:501	FSH24	497:501	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	82	attach	present	512:518	arg1	Asn7					528:531	Asn7	528:531	Asn7	528:531	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	7	83	theme	differential	1253:1264	arg1	bioactivity					1266:1276	differential bioactivity	1253:1276	differential bioactivity	1253:1276	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	5	84	theme	in	759:760	arg1	studies					767:773	in vivo studies	759:773	in vivo studies using Fshb-null mice	759:794	Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities.
31600726	0	85	gly	glycoforms	16:25	arg1	FSH					12:14	Recombinant FSH glycoforms	0:25	Recombinant FSH glycoforms	0:25	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	7	86	gly	glycoforms	1095:1104	arg1	FSH					1091:1093	purified recombinant FSH glycoforms	1070:1104	purified recombinant FSH glycoforms	1070:1104	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	0	87	from	follicles	68:76	arg1	bioactive					31:39	bioactive	31:39	bioactive	31:39	Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles.
31600726	4	88	dep	FSH21/18	654:661	arg1	to					680:681	to	680:681	to	680:681	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	4	88	dep	FSH21/18	654:661	arg1	FSH24					683:687	FSH24	683:687	FSH24	683:687	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	7	89	theme	1-h	1229:1231	arg1	treatment					1233:1241	1-h treatment	1229:1241	1-h treatment	1229:1241	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
31600726	4	90	theme	glycoforms	575:584	arg1	abundance					558:566	The relative abundance	545:566	The relative abundance of FSH glycoforms	545:584	The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women.
31600726	3	91	dep	fully-glycosylated	477:494	arg1	FSH24					497:501	FSH24	497:501	FSH24	497:501	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	3	91	dep	fully-glycosylated	477:494	arg1	glycans					504:510	glycans	504:510	glycans present on both Asn7 and Asn24	504:541	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	2	92	theme	N-linked	200:207	arg1	glycans					209:215	N-linked glycans	200:215	N-linked glycans	200:215	N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit.
31600726	3	93	from	Differences	301:311	arg1	number					320:325	the number	316:325	the number of N-glycans on the FSHβ subunit	316:358	Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24).
31600726	8	94	theme	distinct	1390:1397	arg1	patterns					1410:1417	distinct expression patterns	1390:1417	distinct expression patterns of FSH-responsive genes	1390:1441	Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function.
31600726	7	95	theme	h.	1123:1124	arg1	Analysis					1126:1133	18-20 h. Analysis	1117:1133	18-20 h. Analysis of phosphorylated PKA substrates	1117:1166	In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18-20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose.
29869806	3	0	theme	spectrometry	802:813	arg1	O-glycoproteins					780:794	O-glycoproteins	780:794	O-glycoproteins	780:794	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	0	theme	spectrometry	802:813	arg1	analyses					815:822	mass spectrometry analyses	797:822	mass spectrometry analyses of total serum	797:837	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	1	theme	O-glycoproteins	780:794	arg1	transferrin					725:735	transferrin	725:735	transferrin	725:735	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	1	theme	O-glycoproteins	780:794	arg1	electrophoresis					754:768	two-dimensional electrophoresis	738:768	two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	738:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	1	2	theme	Congenital	168:177	arg1	diseases					239:246	rare autosomal genetic diseases	216:246	rare autosomal genetic diseases affecting the glycosylation of proteins and lipids	216:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	1	2	theme	Congenital	168:177	arg1	disorders					179:187	Congenital disorders	168:187	Congenital disorders of glycosylation (CDG)	168:210	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	0	3	theme	techniques	76:85	arg1	Complementarity					0:14	Complementarity	0:14	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.	0:166	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	3	4	theme	two-dimensional	738:752	arg1	transferrin					725:735	transferrin	725:735	transferrin	725:735	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	4	theme	two-dimensional	738:752	arg1	electrophoresis					754:768	two-dimensional electrophoresis	738:768	two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	738:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	5	theme	gene	953:956	arg1	mutations					958:966	various culprit CDG gene mutations	933:966	various culprit CDG gene mutations	933:966	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	2	6	theme	causative	557:565	arg1	mutations					572:580	causative gene mutations	557:580	causative gene mutations	557:580	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	2	7	theme	CDG-related	306:316	arg1	symptoms					327:334	CDG-related clinical symptoms	306:334	CDG-related clinical symptoms	306:334	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	3	8	theme	mutations	958:966	arg1	determination					916:928	the determination	912:928	the determination of various culprit CDG gene mutations	912:966	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	1	9	theme	proteins	279:286	arg1	glycosylation					262:274	the glycosylation	258:274	the glycosylation of proteins and lipids	258:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	4	10	theme	new	1026:1028	arg1	cases					1034:1038	four particular and new CDG cases	1006:1038	four particular and new CDG cases	1006:1038	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	10	theme	new	1026:1028	arg1	MGAT2-CDG					1051:1059	MGAT2-CDG	1051:1059	MGAT2-CDG	1051:1059	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	10	theme	new	1026:1028	arg1	SLC35A2-CDG					1076:1086	SLC35A2-CDG	1076:1086	SLC35A2-CDG	1076:1086	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	10	theme	new	1026:1028	arg1	SLC35A3-CDG					1093:1103	SLC35A3-CDG	1093:1103	SLC35A3-CDG	1093:1103	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	10	theme	new	1026:1028	arg1	ATP6V0A2-CDG					1062:1073	ATP6V0A2-CDG	1062:1073	ATP6V0A2-CDG	1062:1073	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	3	11	theme	mass	797:800	arg1	O-glycoproteins					780:794	O-glycoproteins	780:794	O-glycoproteins	780:794	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	11	theme	mass	797:800	arg1	analyses					815:822	mass spectrometry analyses	797:822	mass spectrometry analyses of total serum	797:837	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	0	12	dep	diagnosis	95:103	arg1	the					91:93	the	91:93	the	91:93	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	2	13	theme	spectrometric	427:439	arg1	mass					422:425	electrophoretic, mass spectrometric, and gene sequencing techniques	405:471	mass	422:425	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	4	14	theme	cases	1034:1038	arg1	examples					1136:1143	illustrative examples	1123:1143	illustrative examples	1123:1143	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	14	theme	cases	1034:1038	arg1	pathways					994:1001	"Step-by-step" diagnosis pathways	969:1001	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG,	969:1104	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	2	15	theme	definitive	508:517	arg1	diagnosis					523:531	a definitive CDG diagnosis	506:531	a definitive CDG diagnosis	506:531	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	3	16	from	potential	661:669	arg1	electrophoresis					706:720	capillary electrophoresis	696:720	capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	696:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	1	17	theme	glycosylation	192:204	arg1	diseases					239:246	rare autosomal genetic diseases	216:246	rare autosomal genetic diseases affecting the glycosylation of proteins and lipids	216:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	1	17	theme	glycosylation	192:204	arg1	disorders					179:187	Congenital disorders	168:187	Congenital disorders of glycosylation (CDG)	168:210	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	2	18	theme	CDG	519:521	arg1	diagnosis					523:531	a definitive CDG diagnosis	506:531	a definitive CDG diagnosis	506:531	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	1	19	gly	glycosylation	262:274	arg1	lipids					292:297	lipids	292:297	lipids	292:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	1	19	gly	glycosylation	262:274	arg1	proteins					279:286	proteins	279:286	proteins	279:286	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	2	20	theme	biochemical	613:623	arg1	mechanisms					625:634	the underlying biochemical mechanisms	598:634	the underlying biochemical mechanisms	598:634	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	1	21	theme	lipids	292:297	arg1	glycosylation					262:274	the glycosylation	258:274	the glycosylation of proteins and lipids	258:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	2	22	theme	electrophoretic	405:419	arg1	mass					422:425	electrophoretic, mass spectrometric, and gene sequencing techniques	405:471	mass	422:425	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	3	23	theme	total	827:831	arg1	serum					833:837	total serum	827:837	total serum	827:837	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	0	24	theme	congenital	129:138	arg1	disorders					140:148	congenital disorders	129:148	congenital disorders of glycosylation	129:165	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	2	25	theme	sequencing	451:460	arg1	techniques					462:471	electrophoretic, mass spectrometric, and gene sequencing techniques	405:471	techniques	462:471	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	0	26	theme	electrophoretic	19:33	arg1	techniques					76:85	electrophoretic, mass spectrometric, and gene sequencing techniques	19:85	electrophoretic, mass spectrometric, and gene sequencing techniques	19:85	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	3	27	gly	O-glycoproteins	780:794	arg1	O-glycoproteins					780:794	O-glycoproteins	780:794	O-glycoproteins	780:794	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	27	gly	O-glycoproteins	780:794	arg1	analyses					815:822	mass spectrometry analyses	797:822	mass spectrometry analyses of total serum	797:837	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	4	28	theme	particular	1011:1020	arg1	cases					1034:1038	four particular and new CDG cases	1006:1038	four particular and new CDG cases	1006:1038	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	28	theme	particular	1011:1020	arg1	MGAT2-CDG					1051:1059	MGAT2-CDG	1051:1059	MGAT2-CDG	1051:1059	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	28	theme	particular	1011:1020	arg1	SLC35A2-CDG					1076:1086	SLC35A2-CDG	1076:1086	SLC35A2-CDG	1076:1086	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	28	theme	particular	1011:1020	arg1	SLC35A3-CDG					1093:1103	SLC35A3-CDG	1093:1103	SLC35A3-CDG	1093:1103	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	28	theme	particular	1011:1020	arg1	ATP6V0A2-CDG					1062:1073	ATP6V0A2-CDG	1062:1073	ATP6V0A2-CDG	1062:1073	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	2	29	theme	clinical	318:325	arg1	symptoms					327:334	CDG-related clinical symptoms	306:334	CDG-related clinical symptoms	306:334	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	2	30	theme	gene	446:449	arg1	techniques					462:471	electrophoretic, mass spectrometric, and gene sequencing techniques	405:471	techniques	462:471	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	0	31	theme	spectrometric	41:53	arg1	techniques					76:85	electrophoretic, mass spectrometric, and gene sequencing techniques	19:85	electrophoretic, mass spectrometric, and gene sequencing techniques	19:85	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	3	32	dep	N-	773:774	arg1	glycans					848:854	N-linked glycans	839:854	N-linked glycans	839:854	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	32	dep	N-	773:774	arg1	C-III					902:906	apolipoprotein C-III	887:906	apolipoprotein C-III	887:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	33	theme	capillary	696:704	arg1	electrophoresis					706:720	capillary electrophoresis	696:720	capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	696:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	34	theme	various	933:939	arg1	mutations					958:966	various culprit CDG gene mutations	933:966	various culprit CDG gene mutations	933:966	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	1	35	theme	rare	216:219	arg1	diseases					239:246	rare autosomal genetic diseases	216:246	rare autosomal genetic diseases affecting the glycosylation of proteins and lipids	216:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	1	35	theme	rare	216:219	arg1	disorders					179:187	Congenital disorders	168:187	Congenital disorders of glycosylation (CDG)	168:210	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	0	36	theme	mass	36:39	arg1	spectrometric					41:53	mass spectrometric	36:53	mass spectrometric	36:53	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	0	37	theme	disorders	140:148	arg1	diagnosis					95:103	diagnosis	95:103	diagnosis	95:103	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	0	37	theme	disorders	140:148	arg1	characterization					109:124	characterization	109:124	characterization	109:124	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	3	38	theme	integrating	674:684	arg1	data					686:689	integrating data	674:689	integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	674:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	1	39	theme	autosomal	221:229	arg1	diseases					239:246	rare autosomal genetic diseases	216:246	rare autosomal genetic diseases affecting the glycosylation of proteins and lipids	216:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	1	39	theme	autosomal	221:229	arg1	disorders					179:187	Congenital disorders	168:187	Congenital disorders of glycosylation (CDG)	168:210	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	4	40	theme	CDG	1030:1032	arg1	cases					1034:1038	four particular and new CDG cases	1006:1038	four particular and new CDG cases	1006:1038	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	40	theme	CDG	1030:1032	arg1	MGAT2-CDG					1051:1059	MGAT2-CDG	1051:1059	MGAT2-CDG	1051:1059	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	40	theme	CDG	1030:1032	arg1	SLC35A2-CDG					1076:1086	SLC35A2-CDG	1076:1086	SLC35A2-CDG	1076:1086	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	40	theme	CDG	1030:1032	arg1	SLC35A3-CDG					1093:1103	SLC35A3-CDG	1093:1103	SLC35A3-CDG	1093:1103	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	40	theme	CDG	1030:1032	arg1	ATP6V0A2-CDG					1062:1073	ATP6V0A2-CDG	1062:1073	ATP6V0A2-CDG	1062:1073	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	41	theme	"	982:982	arg1	examples					1136:1143	illustrative examples	1123:1143	illustrative examples	1123:1143	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	41	theme	"	982:982	arg1	pathways					994:1001	"Step-by-step" diagnosis pathways	969:1001	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG,	969:1104	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	3	42	theme	data	686:689	arg1	potential					661:669	the potential	657:669	the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations	657:966	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	43	link	N-linked	839:846	arg1	glycans					848:854	N-linked glycans	839:854	N-linked glycans	839:854	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	2	44	theme	gene	567:570	arg1	mutations					572:580	causative gene mutations	557:580	causative gene mutations	557:580	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	3	45	theme	serum	833:837	arg1	O-glycoproteins					780:794	O-glycoproteins	780:794	O-glycoproteins	780:794	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	45	theme	serum	833:837	arg1	analyses					815:822	mass spectrometry analyses	797:822	mass spectrometry analyses of total serum	797:837	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	0	46	theme	glycosylation	153:165	arg1	disorders					140:148	congenital disorders	129:148	congenital disorders of glycosylation	129:165	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	3	47	theme	transferrin	725:735	arg1	electrophoresis					706:720	capillary electrophoresis	696:720	capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	696:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	48	theme	culprit	941:947	arg1	mutations					958:966	various culprit CDG gene mutations	933:966	various culprit CDG gene mutations	933:966	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	49	theme	N-linked	839:846	arg1	glycans					848:854	N-linked glycans	839:854	N-linked glycans	839:854	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	2	50	theme	underlying	602:611	arg1	mechanisms					625:634	the underlying biochemical mechanisms	598:634	the underlying biochemical mechanisms	598:634	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	3	51	from	electrophoresis	706:720	arg1	potential					661:669	the potential	657:669	the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations	657:966	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	51	from	electrophoresis	706:720	arg1	data					686:689	integrating data	674:689	integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	674:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	52	theme	CDG	949:951	arg1	mutations					958:966	various culprit CDG gene mutations	933:966	various culprit CDG gene mutations	933:966	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	1	53	theme	genetic	231:237	arg1	diseases					239:246	rare autosomal genetic diseases	216:246	rare autosomal genetic diseases affecting the glycosylation of proteins and lipids	216:297	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	1	53	theme	genetic	231:237	arg1	disorders					179:187	Congenital disorders	168:187	Congenital disorders of glycosylation (CDG)	168:210	Congenital disorders of glycosylation (CDG) are rare autosomal genetic diseases affecting the glycosylation of proteins and lipids.
29869806	4	54	theme	diagnosis	984:992	arg1	examples					1136:1143	illustrative examples	1123:1143	illustrative examples	1123:1143	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	54	theme	diagnosis	984:992	arg1	pathways					994:1001	"Step-by-step" diagnosis pathways	969:1001	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG,	969:1104	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	3	55	theme	apolipoprotein	887:900	arg1	C-III					902:906	apolipoprotein C-III	887:906	apolipoprotein C-III	887:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	0	56	theme	sequencing	65:74	arg1	techniques					76:85	electrophoretic, mass spectrometric, and gene sequencing techniques	19:85	electrophoretic, mass spectrometric, and gene sequencing techniques	19:85	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	4	57	theme	Step-by-step	970:981	arg1	examples					1136:1143	illustrative examples	1123:1143	illustrative examples	1123:1143	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	57	theme	Step-by-step	970:981	arg1	pathways					994:1001	"Step-by-step" diagnosis pathways	969:1001	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG,	969:1104	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	2	58	theme	mass	422:425	arg1	mandatory					482:490	mandatory	482:490	mandatory	482:490	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	2	58	theme	mass	422:425	arg1	combination					390:400	a combination	388:400	a combination of electrophoretic, mass spectrometric, and gene sequencing techniques	388:471	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	3	59	theme	mucin	860:864	arg1	O-glycosylated					872:885	mucin core1 O-glycosylated	860:885	mucin core1 O-glycosylated	860:885	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	0	60	theme	gene	60:63	arg1	sequencing					65:74	gene sequencing	60:74	gene sequencing	60:74	Complementarity of electrophoretic, mass spectrometric, and gene sequencing techniques for the diagnosis and characterization of congenital disorders of glycosylation.
29869806	2	61	theme	techniques	462:471	arg1	mandatory					482:490	mandatory	482:490	mandatory	482:490	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	2	61	theme	techniques	462:471	arg1	combination					390:400	a combination	388:400	a combination of electrophoretic, mass spectrometric, and gene sequencing techniques	388:471	Since CDG-related clinical symptoms are classically extremely variable and nonspecific, a combination of electrophoretic, mass spectrometric, and gene sequencing techniques is often mandatory for obtaining a definitive CDG diagnosis, as well as identifying causative gene mutations and deciphering the underlying biochemical mechanisms.
29869806	3	62	theme	N-	773:774	arg1	transferrin					725:735	transferrin	725:735	transferrin	725:735	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	62	theme	N-	773:774	arg1	electrophoresis					754:768	two-dimensional electrophoresis	738:768	two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	738:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	63	theme	O-glycosylated	872:885	arg1	transferrin					725:735	transferrin	725:735	transferrin	725:735	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	3	63	theme	O-glycosylated	872:885	arg1	electrophoresis					754:768	two-dimensional electrophoresis	738:768	two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III	738:906	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29869806	4	64	theme	illustrative	1123:1134	arg1	examples					1136:1143	illustrative examples	1123:1143	illustrative examples	1123:1143	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	4	64	theme	illustrative	1123:1134	arg1	pathways					994:1001	"Step-by-step" diagnosis pathways	969:1001	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG,	969:1104	"Step-by-step" diagnosis pathways of four particular and new CDG cases, including MGAT2-CDG, ATP6V0A2-CDG, SLC35A2-CDG, and SLC35A3-CDG, are described as illustrative examples.
29869806	3	65	theme	core1	866:870	arg1	O-glycosylated					872:885	mucin core1 O-glycosylated	860:885	mucin core1 O-glycosylated	860:885	Here, we illustrate the potential of integrating data from capillary electrophoresis of transferrin, two-dimensional electrophoresis of N- and O-glycoproteins, mass spectrometry analyses of total serum N-linked glycans and mucin core1 O-glycosylated apolipoprotein C-III for the determination of various culprit CDG gene mutations.
29665418	8	0	theme	response	1407:1414	arg1	HIPK1					1425:1429	HIPK1	1425:1429	HIPK1	1425:1429	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	8	0	theme	response	1407:1414	arg1	kinases					1416:1422	stress response kinases	1400:1422	stress response kinases (HIPK1)	1400:1430	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	4	1	theme	comparative	642:652	arg1	studies					669:675	comparative and functional studies	642:675	comparative and functional studies	642:675	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	9	2	theme	de	1475:1476	arg1	hundreds					1557:1564	hundreds	1557:1564	hundreds of immune-related genes	1557:1588	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	9	2	theme	de	1475:1476	arg1	repeats					1483:1489	de novo repeats	1475:1489	de novo repeats	1475:1489	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	5	3	theme	error	883:887	arg1	correction					889:898	error correction	883:898	error correction with paired-end Illumina data (x132.9)	883:937	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	8	4	theme	stress	1400:1405	arg1	HIPK1					1425:1429	HIPK1	1425:1429	HIPK1	1425:1429	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	8	4	theme	stress	1400:1405	arg1	kinases					1416:1422	stress response kinases	1400:1422	stress response kinases (HIPK1)	1400:1430	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	6	5	theme	total	1018:1022	arg1	size					1024:1027	a total size	1016:1027	a total size of 614 Mbp	1016:1038	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	3	6	theme	salmon	443:448	arg1	industry					462:469	the salmon aquaculture industry	439:469	the salmon aquaculture industry	439:469	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	8	7	theme	N-linked	1363:1370	arg1	glycosylation					1372:1384	N-linked glycosylation	1363:1384	N-linked glycosylation (ST8SIA6)	1363:1394	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	8	7	theme	N-linked	1363:1370	arg1	ST8SIA6					1387:1393	ST8SIA6	1387:1393	ST8SIA6	1387:1393	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	6	8	theme	repeated	1091:1098	arg1	%					1053:1053	8.5%	1050:1053	8.5% of the genome sequence	1050:1076	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	8	theme	repeated	1091:1098	arg1	elements					1100:1107	known repeated elements	1085:1107	known repeated elements	1085:1107	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	8	theme	repeated	1091:1098	arg1	sequence					1069:1076	the genome sequence	1058:1076	the genome sequence	1058:1076	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	8	9	link	N-linked	1363:1370	arg1	glycosylation					1372:1384	N-linked glycosylation	1363:1384	N-linked glycosylation (ST8SIA6)	1363:1394	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	8	9	link	N-linked	1363:1370	arg1	ST8SIA6					1387:1393	ST8SIA6	1387:1393	ST8SIA6	1387:1393	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	10	10	theme	in-depth	1684:1691	arg1	genomics					1705:1712	in-depth comparative genomics	1684:1712	in-depth comparative genomics as well as population genetic analyses	1684:1751	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	4	11	theme	genome	708:713	arg1	resources					715:723	genome resources	708:723	genome resources generated during the past years	708:755	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	3	12	theme	lice	497:500	arg1	infestation					502:512	sea lice infestation	493:512	sea lice infestation	493:512	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	3	12	theme	lice	497:500	arg1	alternative					520:530	an alternative	517:530	an alternative to chemicals and pharmaceuticals	517:563	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	1	13	theme	successful	115:124	arg1	families					143:150	the most successful and species-rich families	106:150	the most successful and species-rich families of the Perciformes order of teleost fish	106:191	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	3	14	theme	cleaning	319:326	arg1	behaviour					328:336	The cleaning behaviour	315:336	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops),	315:407	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	8	15	theme	increased	1223:1231	arg1	numbers					1238:1244	increased copy numbers	1223:1244	increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1)	1223:1430	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	6	16	theme	genome	1062:1067	arg1	sequence					1069:1076	the genome sequence	1058:1076	the genome sequence	1058:1076	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	3	17	theme	particular	415:424	arg1	interest					426:433	particular interest	415:433	particular interest for the salmon aquaculture industry	415:469	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	4	18	theme	functional	658:667	arg1	studies					669:675	comparative and functional studies	642:675	comparative and functional studies	642:675	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	9	19	theme	immune-related	1569:1582	arg1	genes					1584:1588	immune-related genes	1569:1588	immune-related genes	1569:1588	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	5	20	theme	paired-end	905:914	arg1	x132.9					931:936	x132.9	931:936	x132.9	931:936	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	5	20	theme	paired-end	905:914	arg1	data					925:928	paired-end Illumina data	905:928	paired-end Illumina data (x132.9)	905:937	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	3	21	theme	corkwing	373:380	arg1	wrasse					382:387	corkwing wrasse	373:387	corkwing wrasse (Symphodus melops)	373:406	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	3	21	theme	corkwing	373:380	arg1	melops					400:405	Symphodus melops	390:405	Symphodus melops	390:405	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	4	22	theme	available	604:612	arg1	assemblies					593:602	few genome assemblies	582:602	few genome assemblies available within this fish family for comparative and functional studies	582:675	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	5	23	theme	PacBio	840:845	arg1	sequencing					852:861	PacBio SMRT sequencing	840:861	PacBio SMRT sequencing (x28.8)	840:869	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	5	23	theme	PacBio	840:845	arg1	x28.8					864:868	x28.8	864:868	x28.8	864:868	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	9	24	theme	genes	1584:1588	arg1	hundreds					1557:1564	hundreds	1557:1564	hundreds of immune-related genes	1557:1588	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	9	24	theme	genes	1584:1588	arg1	repeats					1483:1489	de novo repeats	1475:1489	de novo repeats	1475:1489	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	4	25	from	increase	696:703	arg1	resources					715:723	genome resources	708:723	genome resources generated during the past years	708:755	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	5	26	theme	Illumina	916:923	arg1	x132.9					931:936	x132.9	931:936	x132.9	931:936	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	5	26	theme	Illumina	916:923	arg1	data					925:928	paired-end Illumina data	905:928	paired-end Illumina data (x132.9)	905:937	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	1	27	theme	species-rich	130:141	arg1	families					143:150	the most successful and species-rich families	106:150	the most successful and species-rich families of the Perciformes order of teleost fish	106:191	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	0	28	theme	continuous	2:11	arg1	assembly					20:27	A continuous genome assembly	0:27	A continuous genome assembly of the corkwing wrasse (Symphodus melops).	0:70	A continuous genome assembly of the corkwing wrasse (Symphodus melops).
29665418	10	29	theme	Labrus	1651:1656	arg1	wrasse					1643:1648	the ballan wrasse	1632:1648	the ballan wrasse (Labrus bergylta)	1632:1666	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	10	29	theme	Labrus	1651:1656	arg1	bergylta					1658:1665	Labrus bergylta	1651:1665	Labrus bergylta	1651:1665	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	7	30	theme	ray-finned	1177:1186	arg1	species					1193:1199	ray-finned fish species	1177:1199	ray-finned fish species	1177:1199	The genome assembly covers 94.21% of highly conserved genes across ray-finned fish species.
29665418	7	31	theme	genome	1114:1119	arg1	assembly					1121:1128	The genome assembly	1110:1128	The genome assembly	1110:1128	The genome assembly covers 94.21% of highly conserved genes across ray-finned fish species.
29665418	5	32	dep	using	834:838	arg1	followed					871:878	followed	871:878	followed by error correction with paired-end Illumina data (x132.9)	871:937	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	7	33	theme	conserved	1154:1162	arg1	genes					1164:1168	highly conserved genes	1147:1168	highly conserved genes	1147:1168	The genome assembly covers 94.21% of highly conserved genes across ray-finned fish species.
29665418	1	34	theme	families	143:150	arg1	families					143:150	the most successful and species-rich families	106:150	the most successful and species-rich families of the Perciformes order of teleost fish	106:191	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	1	34	theme	families	143:150	arg1	one					99:101	one	99:101	one	99:101	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	1	34	theme	families	143:150	arg1	wrasses					76:82	The wrasses	72:82	The wrasses (Labridae)	72:93	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	6	35	theme	genome	952:957	arg1	assembly					959:966	The present genome assembly	940:966	The present genome assembly	940:966	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	10	36	theme	understudied	1761:1772	arg1	wrasses					1774:1780	the understudied wrasses	1757:1780	the understudied wrasses	1757:1780	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	10	37	theme	new	1596:1598	arg1	resource					1608:1615	This new genomic resource	1591:1615	This new genomic resource	1591:1615	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	5	38	theme	wrasse	827:832	arg1	assembly					802:809	a highly continuous genome assembly	775:809	a highly continuous genome assembly of the corkwing wrasse	775:832	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	9	39	theme	genome	1531:1536	arg1	annotation					1538:1547	genome annotation	1531:1547	genome annotation	1531:1547	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	3	40	theme	sea	493:495	arg1	infestation					502:512	sea lice infestation	493:512	sea lice infestation	493:512	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	3	40	theme	sea	493:495	arg1	alternative					520:530	an alternative	517:530	an alternative to chemicals and pharmaceuticals	517:563	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	0	41	theme	genome	13:18	arg1	assembly					20:27	A continuous genome assembly	0:27	A continuous genome assembly of the corkwing wrasse (Symphodus melops).	0:70	A continuous genome assembly of the corkwing wrasse (Symphodus melops).
29665418	8	42	theme	specific	1246:1253	arg1	numbers					1238:1244	increased copy numbers	1223:1244	increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1)	1223:1430	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	6	43	theme	sequence	1069:1076	arg1	elements					1100:1107	known repeated elements	1085:1107	known repeated elements	1085:1107	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	43	theme	sequence	1069:1076	arg1	%					1053:1053	8.5%	1050:1053	8.5% of the genome sequence	1050:1076	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	43	theme	sequence	1069:1076	arg1	sequence					1069:1076	the genome sequence	1058:1076	the genome sequence	1058:1076	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	2	44	theme	distinct	256:263	arg1	levels					273:278	distinct trophic levels	256:278	distinct trophic levels in coastal waters and coral reefs	256:312	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	9	45	theme	comparative	1436:1446	arg1	analyses					1448:1455	comparative analyses	1436:1455	comparative analyses	1436:1455	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	1	46	theme	Perciformes	159:169	arg1	order					171:175	the Perciformes order	155:175	the Perciformes order of teleost fish	155:191	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	7	47	theme	fish	1188:1191	arg1	species					1193:1199	ray-finned fish species	1177:1199	ray-finned fish species	1177:1199	The genome assembly covers 94.21% of highly conserved genes across ray-finned fish species.
29665418	4	48	theme	genome	586:591	arg1	assemblies					593:602	few genome assemblies	582:602	few genome assemblies available within this fish family for comparative and functional studies	582:675	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	1	49	theme	order	171:175	arg1	families					143:150	the most successful and species-rich families	106:150	the most successful and species-rich families of the Perciformes order of teleost fish	106:191	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	5	50	theme	genome	795:800	arg1	assembly					802:809	a highly continuous genome assembly	775:809	a highly continuous genome assembly of the corkwing wrasse	775:832	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	10	51	theme	comparative	1693:1703	arg1	genomics					1705:1712	in-depth comparative genomics	1684:1712	in-depth comparative genomics as well as population genetic analyses	1684:1751	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	5	52	theme	continuous	784:793	arg1	assembly					802:809	a highly continuous genome assembly	775:809	a highly continuous genome assembly of the corkwing wrasse	775:832	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	4	53	theme	few	582:584	arg1	assemblies					593:602	few genome assemblies	582:602	few genome assemblies available within this fish family for comparative and functional studies	582:675	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	0	54	theme	wrasse	45:50	arg1	assembly					20:27	A continuous genome assembly	0:27	A continuous genome assembly of the corkwing wrasse (Symphodus melops).	0:70	A continuous genome assembly of the corkwing wrasse (Symphodus melops).
29665418	5	55	theme	corkwing	818:825	arg1	wrasse					827:832	the corkwing wrasse	814:832	the corkwing wrasse	814:832	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	8	56	theme	copy	1233:1236	arg1	numbers					1238:1244	increased copy numbers	1223:1244	increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1)	1223:1430	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	10	57	theme	genetic	1736:1742	arg1	analyses					1744:1751	population genetic analyses	1725:1751	in-depth comparative genomics as well as population genetic analyses	1684:1751	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	8	58	theme	adaptive	1317:1324	arg1	processes					1326:1334	adaptive processes	1317:1334	adaptive processes	1317:1334	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	2	59	theme	coral	302:306	arg1	reefs					308:312	coral reefs	302:312	coral reefs	302:312	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	0	60	theme	corkwing	36:43	arg1	melops					63:68	Symphodus melops	53:68	Symphodus melops	53:68	A continuous genome assembly of the corkwing wrasse (Symphodus melops).
29665418	0	60	theme	corkwing	36:43	arg1	wrasse					45:50	the corkwing wrasse	32:50	the corkwing wrasse (Symphodus melops)	32:69	A continuous genome assembly of the corkwing wrasse (Symphodus melops).
29665418	7	61	theme	genes	1164:1168	arg1	%					1142:1142	94.21%	1137:1142	94.21% of highly conserved genes	1137:1168	The genome assembly covers 94.21% of highly conserved genes across ray-finned fish species.
29665418	7	61	theme	genes	1164:1168	arg1	genes					1164:1168	highly conserved genes	1147:1168	highly conserved genes	1147:1168	The genome assembly covers 94.21% of highly conserved genes across ray-finned fish species.
29665418	6	62	theme	Mbp	1036:1038	arg1	size					1024:1027	a total size	1016:1027	a total size of 614 Mbp	1016:1038	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	62	theme	Mbp	1036:1038	arg1	N50 = 461,652 bp					994:1009	N50 = 461,652 bp	994:1009	N50 = 461,652 bp	994:1009	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	62	theme	Mbp	1036:1038	arg1	contigs					985:991	5040 contigs	980:991	5040 contigs (N50 = 461,652 bp)	980:1010	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	8	63	theme	gene	1339:1342	arg1	glycosylation					1372:1384	N-linked glycosylation	1363:1384	N-linked glycosylation (ST8SIA6)	1363:1394	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	8	63	theme	gene	1339:1342	arg1	kinases					1416:1422	stress response kinases	1400:1422	stress response kinases (HIPK1)	1400:1430	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	8	63	theme	gene	1339:1342	arg1	families					1344:1351	gene families	1339:1351	gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1)	1339:1430	We find evidence for increased copy numbers specific for corkwing wrasse possibly highlighting diversification and adaptive processes in gene families including N-linked glycosylation (ST8SIA6) and stress response kinases (HIPK1).
29665418	10	64	theme	population	1725:1734	arg1	analyses					1744:1751	population genetic analyses	1725:1751	in-depth comparative genomics as well as population genetic analyses	1684:1751	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	2	65	theme	morphological	220:232	arg1	diversity					234:242	great morphological diversity	214:242	great morphological diversity	214:242	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	6	66	theme	present	944:950	arg1	assembly					959:966	The present genome assembly	940:966	The present genome assembly	940:966	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	10	67	theme	genomic	1600:1606	arg1	resource					1608:1615	This new genomic resource	1591:1615	This new genomic resource	1591:1615	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	2	68	theme	trophic	265:271	arg1	levels					273:278	distinct trophic levels	256:278	distinct trophic levels in coastal waters and coral reefs	256:312	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	1	69	theme	teleost	180:186	arg1	fish					188:191	teleost fish	180:191	teleost fish	180:191	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	5	70	theme	SMRT	847:850	arg1	sequencing					852:861	PacBio SMRT sequencing	840:861	PacBio SMRT sequencing (x28.8)	840:869	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	5	70	theme	SMRT	847:850	arg1	x28.8					864:868	x28.8	864:868	x28.8	864:868	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	2	71	theme	great	214:218	arg1	diversity					234:242	great morphological diversity	214:242	great morphological diversity	214:242	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	4	72	theme	rapid	690:694	arg1	increase					696:703	the rapid increase	686:703	the rapid increase in genome resources generated during the past years	686:755	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	2	73	theme	coastal	283:289	arg1	waters					291:296	coastal waters	283:296	coastal waters	283:296	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	1	74	theme	fish	188:191	arg1	order					171:175	the Perciformes order	155:175	the Perciformes order of teleost fish	155:191	The wrasses (Labridae) are one of the most successful and species-rich families of the Perciformes order of teleost fish.
29665418	0	75	theme	Symphodus	53:61	arg1	melops					63:68	Symphodus melops	53:68	Symphodus melops	53:68	A continuous genome assembly of the corkwing wrasse (Symphodus melops).
29665418	0	75	theme	Symphodus	53:61	arg1	wrasse					45:50	the corkwing wrasse	32:50	the corkwing wrasse (Symphodus melops)	32:69	A continuous genome assembly of the corkwing wrasse (Symphodus melops).
29665418	2	76	from	levels	273:278	arg1	waters					291:296	coastal waters	283:296	coastal waters	283:296	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	2	76	from	levels	273:278	arg1	reefs					308:312	coral reefs	302:312	coral reefs	302:312	Its members display great morphological diversity, and occupy distinct trophic levels in coastal waters and coral reefs.
29665418	6	77	theme	known	1085:1089	arg1	%					1053:1053	8.5%	1050:1053	8.5% of the genome sequence	1050:1076	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	77	theme	known	1085:1089	arg1	elements					1100:1107	known repeated elements	1085:1107	known repeated elements	1085:1107	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	6	77	theme	known	1085:1089	arg1	sequence					1069:1076	the genome sequence	1058:1076	the genome sequence	1058:1076	The present genome assembly consists of 5040 contigs (N50 = 461,652 bp) and a total size of 614 Mbp, of which 8.5% of the genome sequence encode known repeated elements.
29665418	3	78	theme	aquaculture	450:460	arg1	industry					462:469	the salmon aquaculture industry	439:469	the salmon aquaculture industry	439:469	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	3	79	theme	Symphodus	390:398	arg1	wrasse					382:387	corkwing wrasse	373:387	corkwing wrasse (Symphodus melops)	373:406	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	3	79	theme	Symphodus	390:398	arg1	melops					400:405	Symphodus melops	390:405	Symphodus melops	390:405	The cleaning behaviour displayed by some wrasses, such as corkwing wrasse (Symphodus melops), is of particular interest for the salmon aquaculture industry to combat and control sea lice infestation as an alternative to chemicals and pharmaceuticals.
29665418	5	80	with	correction	889:898	arg1	x132.9					931:936	x132.9	931:936	x132.9	931:936	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	5	80	with	correction	889:898	arg1	data					925:928	paired-end Illumina data	905:928	paired-end Illumina data (x132.9)	905:937	Here, we present a highly continuous genome assembly of the corkwing wrasse using PacBio SMRT sequencing (x28.8) followed by error correction with paired-end Illumina data (x132.9).
29665418	9	81	dep	de	1475:1476	arg1	novo					1478:1481	novo	1478:1481	novo	1478:1481	By comparative analyses, we discover that de novo repeats, often not properly investigated during genome annotation, encode hundreds of immune-related genes.
29665418	4	82	theme	past	746:749	arg1	years					751:755	the past years	742:755	the past years	742:755	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	4	83	theme	fish	626:629	arg1	family					631:636	this fish family	621:636	this fish family for comparative and functional studies	621:675	There are still few genome assemblies available within this fish family for comparative and functional studies, despite the rapid increase in genome resources generated during the past years.
29665418	10	84	theme	ballan	1636:1641	arg1	wrasse					1643:1648	the ballan wrasse	1632:1648	the ballan wrasse (Labrus bergylta)	1632:1666	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
29665418	10	84	theme	ballan	1636:1641	arg1	bergylta					1658:1665	Labrus bergylta	1651:1665	Labrus bergylta	1651:1665	This new genomic resource, together with the ballan wrasse (Labrus bergylta), will allow for in-depth comparative genomics as well as population genetic analyses for the understudied wrasses.
31521187	4	0	theme	glycosylation	715:727	arg1	tunicamycin					677:687	tunicamycin	677:687	tunicamycin	677:687	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	4	0	theme	glycosylation	715:727	arg1	inhibitor					693:701	an inhibitor	690:701	an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants	690:771	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	1	1	theme	sequence-dependent	254:271	arg1	binding					273:279	sequence-dependent binding	254:279	sequence-dependent binding to protein-coding mRNA in eukaryotic cells	254:322	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	6	2	theme	genes	1092:1096	arg1	response					1052:1059	the transcriptional response	1032:1059	the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants	1032:1118	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	6	2	theme	genes	1092:1096	arg1	indistinguishable					1124:1140	indistinguishable	1124:1140	indistinguishable	1124:1140	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	4	3	theme	N-linked	706:713	arg1	glycosylation					715:727	N-linked glycosylation	706:727	N-linked glycosylation	706:727	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	0	4	theme	endoplasmic	102:112	arg1	reticulum					114:122	the endoplasmic reticulum	98:122	the endoplasmic reticulum stress inducer tunicamycin	98:149	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	0	5	from	Deficiency	0:9	arg1	LEAVES1					65:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	5	6	theme	general	984:990	arg1	biogenesis					998:1007	general miRNA biogenesis	984:1007	general miRNA biogenesis	984:1007	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	6	7	from	response	1052:1059	arg1	plants					1113:1118	hyl1 mutant plants	1101:1118	hyl1 mutant plants	1101:1118	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	5	8	theme	miRNA	992:996	arg1	biogenesis					998:1007	general miRNA biogenesis	984:1007	general miRNA biogenesis	984:1007	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	1	9	theme	protein-coding	284:297	arg1	mRNA					299:302	protein-coding mRNA	284:302	protein-coding mRNA	284:302	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	0	10	theme	stress	124:129	arg1	tunicamycin					139:149	the endoplasmic reticulum stress inducer tunicamycin	98:149	the endoplasmic reticulum stress inducer tunicamycin	98:149	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	2	11	theme	biotic	428:433	arg1	responses					442:450	abiotic and biotic stress responses	416:450	abiotic and biotic stress responses	416:450	In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses.
31521187	3	12	theme	endoplasmic	555:565	arg1	ER					578:579	ER	578:579	ER	578:579	The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.
31521187	3	12	theme	endoplasmic	555:565	arg1	reticulum					567:575	endoplasmic reticulum	555:575	the endoplasmic reticulum (ER) stress response in Arabidopsis	551:611	The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.
31521187	5	13	theme	hypersensitive	884:897	arg1	attributable					912:923	attributable	912:923	attributable	912:923	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	13	theme	hypersensitive	884:897	arg1	phenotype					899:907	the hypersensitive phenotype	880:907	the hypersensitive phenotype	880:907	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	6	14	theme	stress-responsive	1074:1090	arg1	genes					1092:1096	select ER stress-responsive genes	1064:1096	select ER stress-responsive genes	1064:1096	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	0	15	theme	reticulum	114:122	arg1	tunicamycin					139:149	the endoplasmic reticulum stress inducer tunicamycin	98:149	the endoplasmic reticulum stress inducer tunicamycin	98:149	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	6	16	theme	wild-type	1155:1163	arg1	plants					1165:1170	wild-type plants	1155:1170	wild-type plants	1155:1170	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	3	17	theme	reticulum	567:575	arg1	response					589:596	the endoplasmic reticulum (ER) stress response	551:596	the endoplasmic reticulum (ER) stress response in Arabidopsis	551:611	The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.
31521187	5	18	from	function	1013:1020	arg1	loss-of-function					932:947	the loss-of-function	928:947	the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function	928:1020	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	3	19	theme	present	457:463	arg1	study					465:469	The present study	453:469	The present study	453:469	The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.
31521187	4	20	theme	wild-type	756:764	arg1	plants					766:771	wild-type plants	756:771	wild-type plants	756:771	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	6	21	theme	hyl1	1101:1104	arg1	plants					1113:1118	hyl1 mutant plants	1101:1118	hyl1 mutant plants	1101:1118	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	2	22	theme	processes	395:403	arg1	plethora					369:376	a plethora	367:376	a plethora of physiological processes, including abiotic and biotic stress responses	367:450	In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses.
31521187	5	23	theme	similar	826:832	arg1	sensitivity					834:844	similar sensitivity	826:844	similar sensitivity to the wild-type	826:861	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	24	from	loss-of-function	932:947	arg1	function					1013:1020	function	1013:1020	function	1013:1020	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	24	from	loss-of-function	932:947	arg1	biogenesis					998:1007	general miRNA biogenesis	984:1007	general miRNA biogenesis	984:1007	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	4	25	link	N-linked	706:713	arg1	glycosylation					715:727	N-linked glycosylation	706:727	N-linked glycosylation	706:727	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	2	26	theme	physiological	381:393	arg1	responses					442:450	abiotic and biotic stress responses	416:450	abiotic and biotic stress responses	416:450	In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses.
31521187	2	26	theme	physiological	381:393	arg1	processes					395:403	physiological processes	381:403	physiological processes	381:403	In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses.
31521187	0	27	theme	double-stranded	18:32	arg1	LEAVES1					65:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	6	28	theme	mutant	1106:1111	arg1	plants					1113:1118	hyl1 mutant plants	1101:1118	hyl1 mutant plants	1101:1118	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	5	29	theme	deficiency	970:979	arg1	loss-of-function					932:947	the loss-of-function	928:947	the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function	928:1020	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	2	30	theme	stress	435:440	arg1	responses					442:450	abiotic and biotic stress responses	416:450	abiotic and biotic stress responses	416:450	In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses.
31521187	1	31	theme	eukaryotic	307:316	arg1	cells					318:322	eukaryotic cells	307:322	eukaryotic cells	307:322	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	0	32	theme	inducer	131:137	arg1	tunicamycin					139:149	the endoplasmic reticulum stress inducer tunicamycin	98:149	the endoplasmic reticulum stress inducer tunicamycin	98:149	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	3	33	theme	stress	582:587	arg1	response					589:596	the endoplasmic reticulum (ER) stress response	551:596	the endoplasmic reticulum (ER) stress response in Arabidopsis	551:611	The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.
31521187	1	34	theme	non-coding	205:214	arg1	microRNA					177:184	OBJECTIVE microRNA	167:184	OBJECTIVE microRNA (miRNA)	167:192	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	1	34	theme	non-coding	205:214	arg1	RNA					216:218	a small non-coding RNA	197:218	a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells	197:322	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	0	35	theme	binding	38:44	arg1	LEAVES1					65:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	0	36	from	sensitivity	83:93	arg1	Arabidopsis					154:164	Arabidopsis	154:164	Arabidopsis	154:164	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	6	37	theme	ER	1071:1072	arg1	genes					1092:1096	select ER stress-responsive genes	1064:1096	select ER stress-responsive genes	1064:1096	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	0	38	theme	RNA	34:36	arg1	LEAVES1					65:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	1	39	from	binding	273:279	arg1	cells					318:322	eukaryotic cells	307:322	eukaryotic cells	307:322	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	6	40	theme	transcriptional	1036:1050	arg1	response					1052:1059	the transcriptional response	1032:1059	the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants	1032:1118	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	6	40	theme	transcriptional	1036:1050	arg1	indistinguishable					1124:1140	indistinguishable	1124:1140	indistinguishable	1124:1140	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	2	41	theme	abiotic	416:422	arg1	responses					442:450	abiotic and biotic stress responses	416:450	abiotic and biotic stress responses	416:450	In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses.
31521187	0	42	theme	HYPONASTIC	54:63	arg1	LEAVES1					65:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	3	43	theme	miRNA-mediated	508:521	arg1	regulation					523:532	miRNA-mediated regulation	508:532	miRNA-mediated regulation	508:532	The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.
31521187	0	44	theme	protein	46:52	arg1	LEAVES1					65:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	the double-stranded RNA binding protein HYPONASTIC LEAVES1	14:71	Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis.
31521187	6	45	theme	signaling	1248:1256	arg1	pathways					1258:1265	the ER stress signaling pathways	1234:1265	the ER stress signaling pathways	1234:1265	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	2	46	theme	important	348:356	arg1	roles					358:362	important roles	348:362	important roles	348:362	In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses.
31521187	5	47	from	deficiency	970:979	arg1	function					1013:1020	function	1013:1020	function	1013:1020	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	47	from	deficiency	970:979	arg1	biogenesis					998:1007	general miRNA biogenesis	984:1007	general miRNA biogenesis	984:1007	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	6	48	theme	stress	1241:1246	arg1	pathways					1258:1265	the ER stress signaling pathways	1234:1265	the ER stress signaling pathways	1234:1265	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	5	49	theme	HYL1	952:955	arg1	loss-of-function					932:947	the loss-of-function	928:947	the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function	928:1020	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	4	50	dep	RESULTS	614:620	arg1	found					625:629	found	625:629	found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants	625:771	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	6	51	theme	ER	1238:1239	arg1	pathways					1258:1265	the ER stress signaling pathways	1234:1265	the ER stress signaling pathways	1234:1265	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	4	52	theme	ER	741:742	arg1	stress					744:749	ER stress	741:749	ER stress	741:749	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	3	53	from	response	589:596	arg1	Arabidopsis					601:611	Arabidopsis	601:611	Arabidopsis	601:611	The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.
31521187	1	54	theme	gene	235:238	arg1	expression					240:249	gene expression	235:249	gene expression	235:249	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	5	55	theme	Other	774:778	arg1	ago1					810:813	ago1	810:813	ago1	810:813	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	55	theme	Other	774:778	arg1	se					803:804	se	803:804	se	803:804	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	55	theme	Other	774:778	arg1	mutants					794:800	Other miRNA-related mutants	774:800	Other miRNA-related mutants	774:800	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	6	56	theme	select	1064:1069	arg1	genes					1092:1096	select ER stress-responsive genes	1064:1096	select ER stress-responsive genes	1064:1096	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	1	57	theme	small	199:203	arg1	microRNA					177:184	OBJECTIVE microRNA	167:184	OBJECTIVE microRNA (miRNA)	167:192	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	1	57	theme	small	199:203	arg1	RNA					216:218	a small non-coding RNA	197:218	a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells	197:322	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	6	58	theme	HYL1	1213:1216	arg1	loss-of-function					1193:1208	the loss-of-function	1189:1208	the loss-of-function of HYL1	1189:1216	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	4	59	theme	mutant	641:646	arg1	plants					648:653	hyl1 mutant plants	636:653	hyl1 mutant plants	636:653	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31521187	5	60	theme	miRNA-related	780:792	arg1	ago1					810:813	ago1	810:813	ago1	810:813	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	60	theme	miRNA-related	780:792	arg1	se					803:804	se	803:804	se	803:804	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	5	60	theme	miRNA-related	780:792	arg1	mutants					794:800	Other miRNA-related mutants	774:800	Other miRNA-related mutants	774:800	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	6	61	from	that	1147:1150	arg1	response					1052:1059	the transcriptional response	1032:1059	the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants	1032:1118	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	6	61	from	that	1147:1150	arg1	indistinguishable					1124:1140	indistinguishable	1124:1140	indistinguishable	1124:1140	However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
31521187	1	62	theme	OBJECTIVE	167:175	arg1	RNA					216:218	a small non-coding RNA	197:218	a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells	197:322	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	1	62	theme	OBJECTIVE	167:175	arg1	miRNA					187:191	miRNA	187:191	miRNA	187:191	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	1	62	theme	OBJECTIVE	167:175	arg1	microRNA					177:184	OBJECTIVE microRNA	167:184	OBJECTIVE microRNA (miRNA)	167:192	OBJECTIVE microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells.
31521187	5	63	from	biogenesis	998:1007	arg1	loss-of-function					932:947	the loss-of-function	928:947	the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function	928:1020	Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function.
31521187	4	64	theme	hyl1	636:639	arg1	plants					648:653	hyl1 mutant plants	636:653	hyl1 mutant plants	636:653	RESULTS We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants.
31489629	7	0	from	OCN	1407:1409	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	9	1	theme	P38	1982:1984	arg1	pathway					1996:2002	the P38 signaling pathway	1978:2002	the P38 signaling pathway	1978:2002	Our data suggest that osteonectin regulates the extracellular matrix mineralization of osteoblasts through the P38 signaling pathway.
31489629	5	2	link	N-linked	775:782	arg1	Glycoproteins					784:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	8	3	theme	noncollagens	1774:1785	arg1	expressions					1759:1769	the protein and gene expressions	1738:1769	expressions	1759:1769	Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect.
31489629	1	4	theme	crucial	185:191	arg1	role					193:196	a crucial role	183:196	a crucial role	183:196	Osteonectin binds strongly to type I collagen and hydroxyapatite and plays a crucial role in extracellular matrix mineralization.
31489629	5	5	dep	DMP1	808:811	arg1	sialophosphoprotein					853:871	dentin sialophosphoprotein	846:871	dentin sialophosphoprotein	846:871	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	5	dep	DMP1	808:811	arg1	MEPE					878:881	MEPE	878:881	MEPE	878:881	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	5	dep	DMP1	808:811	arg1	phosphoglycoprotein					905:923	matrix extracellular phosphoglycoprotein	884:923	matrix extracellular phosphoglycoprotein	884:923	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	5	dep	DMP1	808:811	arg1	protein					829:835	dentine matrix protein 1	814:837	dentine matrix protein 1	814:837	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	5	dep	DMP1	808:811	arg1	DSPP					840:843	DSPP	840:843	DSPP	840:843	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	2	6	theme	osteoblast	328:337	arg1	mineralization					339:352	osteoblast mineralization	328:352	osteoblast mineralization	328:352	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	8	7	theme	SIBLINGs	1791:1798	arg1	expressions					1759:1769	the protein and gene expressions	1738:1769	expressions	1759:1769	Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect.
31489629	5	8	theme	matrix	884:889	arg1	phosphoglycoprotein					905:923	matrix extracellular phosphoglycoprotein	884:923	matrix extracellular phosphoglycoprotein	884:923	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	9	theme	p38	1434:1436	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	10	theme	dentin	846:851	arg1	sialophosphoprotein					853:871	dentin sialophosphoprotein	846:871	dentin sialophosphoprotein	846:871	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	11	theme	protein	587:593	arg1	expressions					595:605	The gene and protein expressions	574:605	expressions	595:605	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	12	gly	phosphoglycoprotein	905:923	arg1	phosphoglycoprotein					905:923	matrix extracellular phosphoglycoprotein	884:923	matrix extracellular phosphoglycoprotein	884:923	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	13	theme	mitogen-activated	697:713	arg1	kinase					723:728	p38 mitogen-activated protein kinase	693:728	p38 mitogen-activated protein kinase	693:728	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	2	14	theme	Previous	238:245	arg1	studies					247:253	Previous studies	238:253	Previous studies	238:253	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	8	15	theme	p38-rhRNA	1833:1841	arg1	transfection					1817:1828	transfection	1817:1828	transfection of p38-rhRNA	1817:1841	Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect.
31489629	1	16	theme	type	138:141	arg1	collagen					145:152	type I collagen	138:152	type I collagen	138:152	Osteonectin binds strongly to type I collagen and hydroxyapatite and plays a crucial role in extracellular matrix mineralization.
31489629	7	17	from	p38	1434:1436	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	18	theme	kinase	723:728	arg1	expressions					595:605	The gene and protein expressions	574:605	expressions	595:605	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	2	19	theme	p38	276:278	arg1	pathway					290:296	p38 signaling pathway	276:296	p38 signaling pathway	276:296	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	2	19	theme	p38	276:278	arg1	regulator					314:322	an important regulator	301:322	an important regulator for osteoblast mineralization	301:352	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	5	20	theme	quantitative	965:976	arg1	reaction					995:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	21	from	osteoblasts	1441:1451	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	22	theme	reverse-transcription	943:963	arg1	reaction					995:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	23	theme	gene	578:581	arg1	expressions					595:605	The gene and protein expressions	574:605	expressions	595:605	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	6	24	theme	intracellular	1054:1066	arg1	assay					1076:1080	intracellular calcium assay	1054:1080	intracellular calcium assay	1054:1080	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	7	25	from	concentrations	1202:1215	arg1	osteoblasts					1220:1230	osteoblasts	1220:1230	osteoblasts	1220:1230	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	0	26	theme	signaling	89:97	arg1	pathway					99:105	P38 signaling pathway	85:105	P38 signaling pathway	85:105	Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway.
31489629	5	27	theme	bone	637:640	arg1	sialoprotein					642:653	bone sialoprotein	637:653	bone sialoprotein	637:653	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	4	28	theme	Sprague-Dawley	553:566	arg1	rats					568:571	neonatal Sprague-Dawley rats	544:571	neonatal Sprague-Dawley rats	544:571	Osteoblasts were isolated and cultured from parietal bones of neonatal Sprague-Dawley rats.
31489629	5	29	theme	Integrin-Binding	751:766	arg1	Glycoproteins					784:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	30	theme	blot	1016:1019	arg1	analysis					1021:1028	western blot analysis	1008:1028	western blot analysis	1008:1028	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	6	31	theme	Alizarin	1031:1038	arg1	staining					1044:1051	Alizarin red staining	1031:1051	Alizarin red staining	1031:1051	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	0	32	theme	osteoblasts	65:75	arg1	mineralization					47:60	the extracellular matrix mineralization	22:60	the extracellular matrix mineralization of osteoblasts	22:75	Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway.
31489629	7	33	theme	BSP	1397:1399	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	34	theme	N-linked	775:782	arg1	Glycoproteins					784:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	35	theme	proteins	622:629	arg1	expressions					595:605	The gene and protein expressions	574:605	expressions	595:605	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	36	theme	OCN	1407:1409	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	4	37	theme	parietal	526:533	arg1	bones					535:539	parietal bones	526:539	parietal bones of neonatal Sprague-Dawley rats	526:571	Osteoblasts were isolated and cultured from parietal bones of neonatal Sprague-Dawley rats.
31489629	0	38	theme	P38	85:87	arg1	pathway					99:105	P38 signaling pathway	85:105	P38 signaling pathway	85:105	Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway.
31489629	3	39	theme	p38	459:461	arg1	pathway					473:479	the p38 signaling pathway	455:479	the p38 signaling pathway	455:479	This study focused on the role of osteonectin in regulating extracellular matrix mineralization via the p38 signaling pathway.
31489629	7	40	theme	above	1250:1254	arg1	indexes					1271:1277	the above mineralization indexes	1246:1277	the above mineralization indexes	1246:1277	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	41	theme	chain	989:993	arg1	reaction					995:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	42	theme	OPN	1402:1404	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	3	43	theme	osteonectin	389:399	arg1	role					381:384	the role	377:384	the role of osteonectin in regulating extracellular matrix mineralization via the p38 signaling pathway	377:479	This study focused on the role of osteonectin in regulating extracellular matrix mineralization via the p38 signaling pathway.
31489629	9	44	theme	osteoblasts	1958:1968	arg1	mineralization					1940:1953	the extracellular matrix mineralization	1915:1953	the extracellular matrix mineralization of osteoblasts	1915:1968	Our data suggest that osteonectin regulates the extracellular matrix mineralization of osteoblasts through the P38 signaling pathway.
31489629	6	45	theme	electron	1100:1107	arg1	microscopy					1109:1118	transmission electron microscopy	1087:1118	transmission electron microscopy	1087:1118	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	6	46	theme	transmission	1087:1098	arg1	microscopy					1109:1118	transmission electron microscopy	1087:1118	transmission electron microscopy	1087:1118	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	0	47	theme	matrix	40:45	arg1	mineralization					47:60	the extracellular matrix mineralization	22:60	the extracellular matrix mineralization of osteoblasts	22:75	Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway.
31489629	3	48	theme	matrix	429:434	arg1	mineralization					436:449	extracellular matrix mineralization	415:449	extracellular matrix mineralization	415:449	This study focused on the role of osteonectin in regulating extracellular matrix mineralization via the p38 signaling pathway.
31489629	5	49	theme	matrix	822:827	arg1	protein					829:835	dentine matrix protein 1	814:837	dentine matrix protein 1	814:837	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	9	50	theme	extracellular	1919:1931	arg1	mineralization					1940:1953	the extracellular matrix mineralization	1915:1953	the extracellular matrix mineralization of osteoblasts	1915:1968	Our data suggest that osteonectin regulates the extracellular matrix mineralization of osteoblasts through the P38 signaling pathway.
31489629	5	51	theme	dentine	814:820	arg1	protein					829:835	dentine matrix protein 1	814:837	dentine matrix protein 1	814:837	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	52	theme	mineralized	1523:1533	arg1	nodules					1535:1541	mineralized nodules	1523:1541	mineralized nodules	1523:1541	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	53	dep	BSP	632:634	arg1	osteopontin					679:689	osteopontin	679:689	osteopontin	679:689	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	53	dep	BSP	632:634	arg1	OPN					674:676	OPN	674:676	OPN	674:676	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	53	dep	BSP	632:634	arg1	OCN					656:658	OCN	656:658	OCN	656:658	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	53	dep	BSP	632:634	arg1	osteocalcin					661:671	osteocalcin	661:671	osteocalcin	661:671	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	53	dep	BSP	632:634	arg1	sialoprotein					642:653	bone sialoprotein	637:653	bone sialoprotein	637:653	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	54	theme	optima	1313:1318	arg1	1 µg/ml					1280:1286	1 µg/ml	1280:1286	1 µg/ml	1280:1286	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	54	theme	optima	1313:1318	arg1	concentration					1332:1344	the optima osteonectin concentration	1309:1344	the optima osteonectin concentration	1309:1344	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	55	dep	proteins	622:629	arg1	DMP1					808:811	DMP1	808:811	DMP1	808:811	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	2	56	theme	important	304:312	arg1	pathway					290:296	p38 signaling pathway	276:296	p38 signaling pathway	276:296	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	2	56	theme	important	304:312	arg1	regulator					314:322	an important regulator	301:322	an important regulator for osteoblast mineralization	301:352	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	8	57	theme	protein	1742:1748	arg1	expressions					1759:1769	the protein and gene expressions	1738:1769	expressions	1759:1769	Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect.
31489629	7	58	theme	protein	1468:1474	arg1	expressions					1476:1486	p-p38 protein expressions	1462:1486	p-p38 protein expressions	1462:1486	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	9	59	theme	signaling	1986:1994	arg1	pathway					1996:2002	the P38 signaling pathway	1978:2002	the P38 signaling pathway	1978:2002	Our data suggest that osteonectin regulates the extracellular matrix mineralization of osteoblasts through the P38 signaling pathway.
31489629	8	60	theme	gene	1754:1757	arg1	expressions					1759:1769	the protein and gene expressions	1738:1769	expressions	1759:1769	Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect.
31489629	1	61	theme	extracellular	201:213	arg1	mineralization					222:235	extracellular matrix mineralization	201:235	extracellular matrix mineralization	201:235	Osteonectin binds strongly to type I collagen and hydroxyapatite and plays a crucial role in extracellular matrix mineralization.
31489629	5	62	theme	SIBLINGs	735:742	arg1	expressions					595:605	The gene and protein expressions	574:605	expressions	595:605	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	63	theme	p38	693:695	arg1	kinase					723:728	p38 mitogen-activated protein kinase	693:728	p38 mitogen-activated protein kinase	693:728	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	64	theme	DSPP	1424:1427	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	65	theme	protein	715:721	arg1	kinase					723:728	p38 mitogen-activated protein kinase	693:728	p38 mitogen-activated protein kinase	693:728	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	2	66	theme	signaling	280:288	arg1	pathway					290:296	p38 signaling pathway	276:296	p38 signaling pathway	276:296	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	2	66	theme	signaling	280:288	arg1	regulator					314:322	an important regulator	301:322	an important regulator for osteoblast mineralization	301:352	Previous studies have also shown that p38 signaling pathway is an important regulator for osteoblast mineralization.
31489629	5	67	theme	noncollagen	610:620	arg1	BSP					632:634	BSP	632:634	BSP	632:634	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	67	theme	noncollagen	610:620	arg1	proteins					622:629	noncollagen proteins	610:629	noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin)	610:690	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	1	68	theme	I	143:143	arg1	collagen					145:152	type I collagen	138:152	type I collagen	138:152	Osteonectin binds strongly to type I collagen and hydroxyapatite and plays a crucial role in extracellular matrix mineralization.
31489629	7	69	theme	MEPE	1418:1421	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	70	theme	Glycoproteins	784:796	arg1	expressions					595:605	The gene and protein expressions	574:605	expressions	595:605	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	71	theme	extracellular	891:903	arg1	phosphoglycoprotein					905:923	matrix extracellular phosphoglycoprotein	884:923	matrix extracellular phosphoglycoprotein	884:923	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	6	72	theme	calcium	1068:1074	arg1	assay					1076:1080	intracellular calcium assay	1054:1080	intracellular calcium assay	1054:1080	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	4	73	theme	neonatal	544:551	arg1	rats					568:571	neonatal Sprague-Dawley rats	544:571	neonatal Sprague-Dawley rats	544:571	Osteoblasts were isolated and cultured from parietal bones of neonatal Sprague-Dawley rats.
31489629	7	74	theme	DMP1	1412:1415	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	5	75	theme	members	799:805	arg1	expressions					595:605	The gene and protein expressions	574:605	expressions	595:605	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	8	76	theme	opposite	1854:1861	arg1	effect					1863:1868	the opposite effect	1850:1868	the opposite effect	1850:1868	Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect.
31489629	7	77	theme	specific	1600:1607	arg1	inhibitor					1609:1617	a specific inhibitor	1598:1617	a specific inhibitor for p38	1598:1625	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	4	78	theme	rats	568:571	arg1	bones					535:539	parietal bones	526:539	parietal bones of neonatal Sprague-Dawley rats	526:571	Osteoblasts were isolated and cultured from parietal bones of neonatal Sprague-Dawley rats.
31489629	5	79	theme	Small	745:749	arg1	Glycoproteins					784:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	5	80	theme	western	1008:1014	arg1	analysis					1021:1028	western blot analysis	1008:1028	western blot analysis	1008:1028	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	6	81	theme	red	1040:1042	arg1	staining					1044:1051	Alizarin red staining	1031:1051	Alizarin red staining	1031:1051	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	7	82	theme	mineralization	1256:1269	arg1	indexes					1271:1277	the above mineralization indexes	1246:1277	the above mineralization indexes	1246:1277	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	1	83	theme	matrix	215:220	arg1	mineralization					222:235	extracellular matrix mineralization	201:235	extracellular matrix mineralization	201:235	Osteonectin binds strongly to type I collagen and hydroxyapatite and plays a crucial role in extracellular matrix mineralization.
31489629	7	84	from	DMP1	1412:1415	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	8	85	dep	noncollagens	1774:1785	arg1	members					1800:1806	members	1800:1806	members	1800:1806	Furthermore, osteoblasts transfected with Ad-p38 also significantly upregulated the protein and gene expressions of noncollagens and SIBLINGs members, whereas transfection of p38-rhRNA showed the opposite effect.
31489629	5	86	theme	LIgand	768:773	arg1	Glycoproteins					784:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	Small Integrin-Binding LIgand N-linked Glycoproteins	745:796	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	6	87	used	used	1125:1128	arg2	assay					1076:1080	intracellular calcium assay	1054:1080	intracellular calcium assay	1054:1080	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	6	87	used	used	1125:1128	arg2	microscopy					1109:1118	transmission electron microscopy	1087:1118	transmission electron microscopy	1087:1118	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	6	87	used	used	1125:1128	arg2	staining					1044:1051	Alizarin red staining	1031:1051	Alizarin red staining	1031:1051	Alizarin red staining, intracellular calcium assay, and transmission electron microscopy were used to detect mineralization.
31489629	5	88	theme	polymerase	978:987	arg1	reaction					995:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	reverse-transcription quantitative polymerase chain reaction	943:1002	The gene and protein expressions of noncollagen proteins (BSP, bone sialoprotein; OCN, osteocalcin; OPN, osteopontin), p38 mitogen-activated protein kinase, and SIBLINGs (Small Integrin-Binding LIgand N-linked Glycoproteins) members (DMP1, dentine matrix protein 1, DSPP, dentin sialophosphoprotein, and MEPE, matrix extracellular phosphoglycoprotein) were detected by reverse-transcription quantitative polymerase chain reaction and western blot analysis.
31489629	7	89	from	MEPE	1418:1421	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	3	90	theme	extracellular	415:427	arg1	mineralization					436:449	extracellular matrix mineralization	415:449	extracellular matrix mineralization	415:449	This study focused on the role of osteonectin in regulating extracellular matrix mineralization via the p38 signaling pathway.
31489629	3	91	theme	signaling	463:471	arg1	pathway					473:479	the p38 signaling pathway	455:479	the p38 signaling pathway	455:479	This study focused on the role of osteonectin in regulating extracellular matrix mineralization via the p38 signaling pathway.
31489629	0	92	theme	extracellular	26:38	arg1	mineralization					47:60	the extracellular matrix mineralization	22:60	the extracellular matrix mineralization of osteoblasts	22:75	Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway.
31489629	7	93	from	DSPP	1424:1427	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	94	dep	determined	1292:1301	arg1	enhanced					1562:1569	enhanced	1562:1569	were significantly enhanced	1543:1569	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	94	dep	determined	1292:1301	arg1	increased					1512:1520	increased	1512:1520	were also significantly increased	1488:1520	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	95	theme	gene	1377:1380	arg1	expressions					1382:1392	gene expressions	1377:1392	gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts	1377:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	96	theme	different	1192:1200	arg1	concentrations					1202:1215	different concentrations	1192:1215	different concentrations in osteoblasts	1192:1230	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	97	from	expressions	1382:1392	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	98	from	BSP	1397:1399	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	9	99	theme	matrix	1933:1938	arg1	mineralization					1940:1953	the extracellular matrix mineralization	1915:1953	the extracellular matrix mineralization of osteoblasts	1915:1968	Our data suggest that osteonectin regulates the extracellular matrix mineralization of osteoblasts through the P38 signaling pathway.
31489629	7	100	from	OPN	1402:1404	arg1	osteoblasts					1441:1451	osteoblasts	1441:1451	osteoblasts	1441:1451	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	101	theme	osteonectin	1320:1330	arg1	1 µg/ml					1280:1286	1 µg/ml	1280:1286	1 µg/ml	1280:1286	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	101	theme	osteonectin	1320:1330	arg1	concentration					1332:1344	the optima osteonectin concentration	1309:1344	the optima osteonectin concentration	1309:1344	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31489629	7	102	dep	SB203580	1588:1595	arg1	inhibitor					1609:1617	a specific inhibitor	1598:1617	a specific inhibitor for p38	1598:1625	Initially, by adding osteonectin at different concentrations in osteoblasts and detecting the above mineralization indexes, 1 µg/ml was determined to be the optima osteonectin concentration, which significantly increased gene expressions of BSP, OPN, OCN, DMP1, MEPE, DSPP, and p38 in osteoblasts, p38 and p-p38 protein expressions were also significantly increased, mineralized nodules were significantly enhanced; when added with SB203580 (a specific inhibitor for p38) these effects were inhibited.
31405482	10	0	theme	papain-treated	1954:1967	arg1	semen					1969:1973	bromelain- and papain-treated semen	1939:1973	bromelain- and papain-treated semen	1939:1973	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	3	1	theme	ejaculate	519:527	arg1	portion					499:505	A portion	497:505	A portion of each raw ejaculate	497:527	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	1	2	theme	morpho-functional	274:290	arg1	properties					311:320	morpho-functional and glycan surface properties	274:320	properties	311:320	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	9	3	theme	entire	1698:1703	arg1	surface					1711:1717	the entire sperm surface	1694:1717	the entire sperm surface	1694:1717	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	10	4	theme	assisted	2000:2007	arg1	technologies					2022:2033	camel assisted reproductive technologies	1994:2033	camel assisted reproductive technologies	1994:2033	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	1	5	theme	glycan	296:301	arg1	properties					311:320	morpho-functional and glycan surface properties	274:320	properties	311:320	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	9	6	theme	surface	1711:1717	arg1	content					1683:1689	the N-linked glycan content	1663:1689	the N-linked glycan content of the entire sperm surface	1663:1717	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	3	7	theme	0.1 mg/mL	719:727	arg1	papain					729:734	0.1 mg/mL papain	719:734	0.1 mg/mL papain	719:734	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	7	theme	0.1 mg/mL	719:727	arg1	treatments					686:695	the following liquefaction treatments	659:695	the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain	659:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	8	theme	sperm	547:551	arg1	traits					580:585	sperm physical and morphological traits	547:585	sperm physical and morphological traits	547:585	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	9	theme	U/mL	741:744	arg1	treatments					686:695	the following liquefaction treatments	659:695	the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain	659:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	9	theme	U/mL	741:744	arg1	bromelain					746:754	5 U/mL bromelain	739:754	5 U/mL bromelain	739:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	0	10	theme	spermatozoa	126:136	arg1	physical					63:70	physical	63:70	physical	63:70	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	1	11	theme	camel	219:223	arg1	viscosity					231:239	camel semen viscosity	219:239	camel semen viscosity	219:239	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	8	12	theme	increased	1503:1511	arg1	velocity					1527:1534	increased straight-line velocity	1503:1534	increased straight-line velocity (VSL, μm/s)	1503:1546	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	12	theme	increased	1503:1511	arg1	abnormalities					1488:1500	secondary sperm abnormalities	1472:1500	secondary sperm abnormalities	1472:1500	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	3	13	dep	treatments	686:695	arg1	papain					729:734	0.1 mg/mL papain	719:734	0.1 mg/mL papain	719:734	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	13	dep	treatments	686:695	arg1	bromelain					746:754	5 U/mL bromelain	739:754	5 U/mL bromelain	739:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	13	dep	treatments	686:695	arg1	treatments					686:695	the following liquefaction treatments	659:695	the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain	659:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	13	dep	treatments	686:695	arg1	control					698:704	control	698:704	control (untreated)	698:716	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	9	14	theme	little	1765:1770	arg1	change					1772:1777	little change	1765:1777	little change in N-acetylgalactosamine and fucose terminating glycans	1765:1833	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	1	15	from	ramifications	257:269	arg1	diluent					198:204	the diluent	194:204	the diluent for reducing camel semen viscosity	194:239	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	1	15	from	ramifications	257:269	arg1	properties					311:320	morpho-functional and glycan surface properties	274:320	properties	311:320	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	3	16	theme	other	600:604	arg1	portion					606:612	the other portion	596:612	the other portion	596:612	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	7	17	theme	bromelain	1248:1256	arg1	supplementation					1258:1272	bromelain supplementation	1248:1272	bromelain supplementation	1248:1272	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	4	18	contain	containing	808:817	arg2	E-64					835:838	the anti-enzyme E-64	819:838	the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation	819:911	All samples were diluted with Tris-lactose diluent containing the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation.
31405482	4	18	contain	containing	808:817	arg1	diluent					800:806	Tris-lactose diluent	787:806	Tris-lactose diluent containing the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation	787:911	All samples were diluted with Tris-lactose diluent containing the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation.
31405482	9	19	from	analysis	1609:1616	arg1	Results					1585:1591	Results	1585:1591	Results from the glycan analysis	1585:1616	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	6	20	theme	glycocalyx	1061:1070	arg1	pattern					1072:1078	The sperm surface glycocalyx pattern	1043:1078	The sperm surface glycocalyx pattern	1043:1078	The sperm surface glycocalyx pattern was evaluated with a panel of 14 fluorescent lectins.
31405482	10	21	theme	Functional	1868:1877	arg1	studies					1879:1885	Functional studies	1868:1885	Functional studies	1868:1885	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	5	22	theme	physical	924:931	arg1	properties					947:956	Post-thaw physical and kinematic properties	914:956	Post-thaw physical and kinematic properties of spermatozoa	914:971	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	9	23	from	change	1772:1777	arg1	fucose					1808:1813	fucose	1808:1813	fucose	1808:1813	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	9	23	from	change	1772:1777	arg1	N-acetylgalactosamine					1782:1802	N-acetylgalactosamine	1782:1802	N-acetylgalactosamine	1782:1802	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	9	24	theme	terminating	1815:1825	arg1	glycans					1827:1833	terminating glycans	1815:1833	terminating glycans	1815:1833	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	5	25	theme	kinematic	937:945	arg1	properties					947:956	Post-thaw physical and kinematic properties	914:956	Post-thaw physical and kinematic properties of spermatozoa	914:971	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	0	26	from	Ramifications	0:12	arg1	kinematic					73:81	kinematic	73:81	kinematic	73:81	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	0	26	from	Ramifications	0:12	arg1	glyco-pattern					95:107	surface glyco-pattern	87:107	surface glyco-pattern	87:107	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	0	26	from	Ramifications	0:12	arg1	physical					63:70	physical	63:70	physical	63:70	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	0	27	theme	surface	87:93	arg1	glyco-pattern					95:107	surface glyco-pattern	87:107	surface glyco-pattern	87:107	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	5	28	theme	analysis	1019:1026	arg1	system					1035:1040	a computer-assisted sperm analysis (CASA) system	993:1040	a computer-assisted sperm analysis (CASA) system	993:1040	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	9	29	theme	tail	1842:1845	arg1	region					1847:1852	the tail region	1838:1852	the tail region of the sperm	1838:1865	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	8	30	theme	papain-treated	1405:1418	arg1	samples					1432:1438	papain-treated and control samples	1405:1438	papain-treated and control samples	1405:1438	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	3	31	dep	control	698:704	arg1	untreated					707:715	untreated	707:715	untreated	707:715	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	0	32	theme	camel	48:52	arg1	semen					54:58	camel semen	48:58	camel semen	48:58	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	9	33	theme	glycan	1602:1607	arg1	analysis					1609:1616	the glycan analysis	1598:1616	the glycan analysis	1598:1616	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	8	34	theme	spermatozoa	1572:1582	arg1	velocity					1527:1534	increased straight-line velocity	1503:1534	increased straight-line velocity (VSL, μm/s)	1503:1546	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	34	theme	spermatozoa	1572:1582	arg1	%					1566:1566	%	1566:1566	%	1566:1566	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	34	theme	spermatozoa	1572:1582	arg1	abnormalities					1488:1500	secondary sperm abnormalities	1472:1500	secondary sperm abnormalities	1472:1500	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	34	theme	spermatozoa	1572:1582	arg1	straightness					1552:1563	straightness	1552:1563	straightness (%) of spermatozoa	1552:1582	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	35	theme	control	1424:1430	arg1	samples					1432:1438	papain-treated and control samples	1405:1438	papain-treated and control samples	1405:1438	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	10	36	theme	camel	1994:1998	arg1	technologies					2022:2033	camel assisted reproductive technologies	1994:2033	camel assisted reproductive technologies	1994:2033	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	1	37	theme	surface	303:309	arg1	properties					311:320	morpho-functional and glycan surface properties	274:320	properties	311:320	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	7	38	dep	variables	1293:1301	arg1	variables					1293:1301	the variables	1289:1301	the variables: normal sperm, intact acrosome and intact sperm cell membrane	1289:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	38	dep	variables	1293:1301	arg1	sperm					1311:1315	normal sperm	1304:1315	normal sperm	1304:1315	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	38	dep	variables	1293:1301	arg1	membrane					1356:1363	intact sperm cell membrane	1338:1363	intact sperm cell membrane	1338:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	38	dep	variables	1293:1301	arg1	acrosome					1325:1332	intact acrosome	1318:1332	intact acrosome	1318:1332	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	9	39	theme	sperm	1861:1865	arg1	region					1847:1852	the tail region	1838:1852	the tail region of the sperm	1838:1865	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	0	40	theme	protease-based	17:30	arg1	liquefaction					32:43	protease-based liquefaction	17:43	protease-based liquefaction of camel semen	17:58	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	5	41	theme	computer-assisted	995:1011	arg1	analysis					1019:1026	computer-assisted sperm analysis	995:1026	a computer-assisted sperm analysis (CASA) system	993:1040	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	5	41	theme	computer-assisted	995:1011	arg1	CASA					1029:1032	CASA	1029:1032	CASA	1029:1032	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	7	42	theme	cell	1351:1354	arg1	variables					1293:1301	the variables	1289:1301	the variables: normal sperm, intact acrosome and intact sperm cell membrane	1289:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	42	theme	cell	1351:1354	arg1	membrane					1356:1363	intact sperm cell membrane	1338:1363	intact sperm cell membrane	1338:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	3	43	theme	following	663:671	arg1	treatments					686:695	the following liquefaction treatments	659:695	the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain	659:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	43	theme	following	663:671	arg1	bromelain					746:754	5 U/mL bromelain	739:754	5 U/mL bromelain	739:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	43	theme	following	663:671	arg1	papain					729:734	0.1 mg/mL papain	719:734	0.1 mg/mL papain	719:734	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	43	theme	following	663:671	arg1	control					698:704	control	698:704	control (untreated)	698:716	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	9	44	with	treatment	1732:1740	arg1	proteases					1747:1755	proteases	1747:1755	proteases	1747:1755	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	7	45	theme	viscosity	1196:1204	arg1	elimination					1175:1185	elimination	1175:1185	elimination of semen viscosity	1175:1204	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	1	46	theme	spermatozoa	339:349	arg1	properties					311:320	morpho-functional and glycan surface properties	274:320	properties	311:320	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	7	47	theme	intact	1338:1343	arg1	variables					1293:1301	the variables	1289:1301	the variables: normal sperm, intact acrosome and intact sperm cell membrane	1289:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	47	theme	intact	1338:1343	arg1	membrane					1356:1363	intact sperm cell membrane	1338:1363	intact sperm cell membrane	1338:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	0	48	theme	semen	54:58	arg1	liquefaction					32:43	protease-based liquefaction	17:43	protease-based liquefaction of camel semen	17:58	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	8	49	theme	sperm	1482:1486	arg1	velocity					1527:1534	increased straight-line velocity	1503:1534	increased straight-line velocity (VSL, μm/s)	1503:1546	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	49	theme	sperm	1482:1486	arg1	abnormalities					1488:1500	secondary sperm abnormalities	1472:1500	secondary sperm abnormalities	1472:1500	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	49	theme	sperm	1482:1486	arg1	straightness					1552:1563	straightness	1552:1563	straightness (%) of spermatozoa	1552:1582	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	9	50	theme	N-linked	1667:1674	arg1	content					1683:1689	the N-linked glycan content	1663:1689	the N-linked glycan content of the entire sperm surface	1663:1717	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	10	51	theme	fertility	1920:1928	arg1	rates					1930:1934	the sperm fertility rates	1910:1934	the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies	1910:2033	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	1	52	theme	subsequent	246:255	arg1	ramifications					257:269	subsequent ramifications	246:269	subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa	246:349	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	6	53	theme	sperm	1047:1051	arg1	pattern					1072:1078	The sperm surface glycocalyx pattern	1043:1078	The sperm surface glycocalyx pattern	1043:1078	The sperm surface glycocalyx pattern was evaluated with a panel of 14 fluorescent lectins.
31405482	7	54	theme	normal	1304:1309	arg1	variables					1293:1301	the variables	1289:1301	the variables: normal sperm, intact acrosome and intact sperm cell membrane	1289:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	54	theme	normal	1304:1309	arg1	sperm					1311:1315	normal sperm	1304:1315	normal sperm	1304:1315	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	10	55	theme	semen	1969:1973	arg1	rates					1930:1934	the sperm fertility rates	1910:1934	the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies	1910:2033	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	3	56	theme	raw	515:517	arg1	ejaculate					519:527	each raw ejaculate	510:527	each raw ejaculate	510:527	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	6	57	theme	lectins	1125:1131	arg1	panel					1101:1105	a panel	1099:1105	a panel of 14 fluorescent lectins	1099:1131	The sperm surface glycocalyx pattern was evaluated with a panel of 14 fluorescent lectins.
31405482	3	58	theme	physical	553:560	arg1	traits					580:585	sperm physical and morphological traits	547:585	sperm physical and morphological traits	547:585	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	9	59	theme	sperm	1705:1709	arg1	surface					1711:1717	the entire sperm surface	1694:1717	the entire sperm surface	1694:1717	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	3	60	theme	5	739:739	arg1	U/mL					741:744	U/mL	741:744	U/mL	741:744	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	61	theme	morphological	566:578	arg1	traits					580:585	sperm physical and morphological traits	547:585	sperm physical and morphological traits	547:585	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	9	62	link	N-linked	1667:1674	arg1	content					1683:1689	the N-linked glycan content	1663:1689	the N-linked glycan content of the entire sperm surface	1663:1717	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	8	63	theme	straight-line	1513:1525	arg1	velocity					1527:1534	increased straight-line velocity	1503:1534	increased straight-line velocity (VSL, μm/s)	1503:1546	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	63	theme	straight-line	1513:1525	arg1	abnormalities					1488:1500	secondary sperm abnormalities	1472:1500	secondary sperm abnormalities	1472:1500	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	10	64	theme	reproductive	2009:2020	arg1	technologies					2022:2033	camel assisted reproductive technologies	1994:2033	camel assisted reproductive technologies	1994:2033	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	1	65	theme	semen	225:229	arg1	viscosity					231:239	camel semen viscosity	219:239	camel semen viscosity	219:239	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	10	66	from	application	1979:1989	arg1	technologies					2022:2033	camel assisted reproductive technologies	1994:2033	camel assisted reproductive technologies	1994:2033	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	5	67	theme	spermatozoa	961:971	arg1	properties					947:956	Post-thaw physical and kinematic properties	914:956	Post-thaw physical and kinematic properties of spermatozoa	914:971	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	5	68	theme	Post-thaw	914:922	arg1	properties					947:956	Post-thaw physical and kinematic properties	914:956	Post-thaw physical and kinematic properties of spermatozoa	914:971	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	6	69	theme	surface	1053:1059	arg1	pattern					1072:1078	The sperm surface glycocalyx pattern	1043:1078	The sperm surface glycocalyx pattern	1043:1078	The sperm surface glycocalyx pattern was evaluated with a panel of 14 fluorescent lectins.
31405482	7	70	from	elimination	1175:1185	arg1	effective					1162:1170	effective	1162:1170	effective	1162:1170	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	9	71	dep	N-acetylgalactosamine	1782:1802	arg1	glycans					1827:1833	terminating glycans	1815:1833	terminating glycans	1815:1833	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
31405482	1	72	theme	different	171:179	arg1	proteases					181:189	different proteases	171:189	different proteases in the diluent for reducing camel semen viscosity	171:239	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	8	73	theme	Bromelain	1366:1374	arg1	supplementation					1376:1390	Bromelain supplementation	1366:1390	Bromelain supplementation	1366:1390	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	74	theme	secondary	1472:1480	arg1	velocity					1527:1534	increased straight-line velocity	1503:1534	increased straight-line velocity (VSL, μm/s)	1503:1546	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	74	theme	secondary	1472:1480	arg1	abnormalities					1488:1500	secondary sperm abnormalities	1472:1500	secondary sperm abnormalities	1472:1500	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	74	theme	secondary	1472:1480	arg1	straightness					1552:1563	straightness	1552:1563	straightness (%) of spermatozoa	1552:1582	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	1	75	from	proteases	181:189	arg1	diluent					198:204	the diluent	194:204	the diluent for reducing camel semen viscosity	194:239	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	1	75	from	proteases	181:189	arg1	properties					311:320	morpho-functional and glycan surface properties	274:320	properties	311:320	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	5	76	theme	sperm	1013:1017	arg1	analysis					1019:1026	computer-assisted sperm analysis	995:1026	a computer-assisted sperm analysis (CASA) system	993:1040	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	5	76	theme	sperm	1013:1017	arg1	CASA					1029:1032	CASA	1029:1032	CASA	1029:1032	Post-thaw physical and kinematic properties of spermatozoa were analyzed using a computer-assisted sperm analysis (CASA) system.
31405482	0	77	theme	cryopreserved	112:124	arg1	spermatozoa					126:136	cryopreserved spermatozoa	112:136	cryopreserved spermatozoa	112:136	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	2	78	dep	season	471:476	arg1	March					489:493	March	489:493	March	489:493	Ejaculates (n = 48) were collected from three adult camels, Camelus dromedarius, during the breeding season (January - March).
31405482	2	78	dep	season	471:476	arg1	January					479:485	January	479:485	January	479:485	Ejaculates (n = 48) were collected from three adult camels, Camelus dromedarius, during the breeding season (January - March).
31405482	6	79	theme	fluorescent	1113:1123	arg1	lectins					1125:1131	14 fluorescent lectins	1110:1131	14 fluorescent lectins	1110:1131	The sperm surface glycocalyx pattern was evaluated with a panel of 14 fluorescent lectins.
31405482	7	80	theme	negative	1219:1226	arg1	correlation					1228:1238	a negative correlation	1217:1238	a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane	1217:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	2	81	theme	adult	416:420	arg1	camels					422:427	three adult camels	410:427	three adult camels	410:427	Ejaculates (n = 48) were collected from three adult camels, Camelus dromedarius, during the breeding season (January - March).
31405482	0	82	theme	liquefaction	32:43	arg1	Ramifications					0:12	Ramifications	0:12	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.	0:137	Ramifications of protease-based liquefaction of camel semen on physical, kinematic and surface glyco-pattern of cryopreserved spermatozoa.
31405482	7	83	theme	sperm	1345:1349	arg1	variables					1293:1301	the variables	1289:1301	the variables: normal sperm, intact acrosome and intact sperm cell membrane	1289:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	83	theme	sperm	1345:1349	arg1	membrane					1356:1363	intact sperm cell membrane	1338:1363	intact sperm cell membrane	1338:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	2	84	theme	breeding	462:469	arg1	season					471:476	the breeding season	458:476	the breeding season (January - March)	458:494	Ejaculates (n = 48) were collected from three adult camels, Camelus dromedarius, during the breeding season (January - March).
31405482	10	85	theme	sperm	1914:1918	arg1	rates					1930:1934	the sperm fertility rates	1910:1934	the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies	1910:2033	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	7	86	theme	semen	1190:1194	arg1	viscosity					1196:1204	semen viscosity	1190:1204	semen viscosity	1190:1204	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	1	87	theme	cryopreserved	325:337	arg1	spermatozoa					339:349	cryopreserved spermatozoa	325:349	cryopreserved spermatozoa	325:349	The efficiency of incorporating different proteases in the diluent for reducing camel semen viscosity, and subsequent ramifications on morpho-functional and glycan surface properties of cryopreserved spermatozoa were investigated.
31405482	4	88	theme	anti-enzyme	823:833	arg1	E-64					835:838	the anti-enzyme E-64	819:838	the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation	819:911	All samples were diluted with Tris-lactose diluent containing the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation.
31405482	8	89	dep	velocity	1527:1534	arg1	μm/s					1542:1545	μm/s	1542:1545	μm/s	1542:1545	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	8	89	dep	velocity	1527:1534	arg1	VSL					1537:1539	VSL	1537:1539	VSL	1537:1539	Bromelain supplementation, compared to papain-treated and control samples, was positively correlated with secondary sperm abnormalities, increased straight-line velocity (VSL, μm/s) and straightness (%) of spermatozoa.
31405482	7	90	theme	intact	1318:1323	arg1	variables					1293:1301	the variables	1289:1301	the variables: normal sperm, intact acrosome and intact sperm cell membrane	1289:1363	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	90	theme	intact	1318:1323	arg1	acrosome					1325:1332	intact acrosome	1318:1332	intact acrosome	1318:1332	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	7	91	from	effective	1162:1170	arg1	elimination					1175:1185	elimination	1175:1185	elimination of semen viscosity	1175:1204	Although bromelain was more effective in elimination of semen viscosity, there was a negative correlation between bromelain supplementation and values for the variables: normal sperm, intact acrosome and intact sperm cell membrane.
31405482	10	92	theme	bromelain-	1939:1948	arg1	semen					1969:1973	bromelain- and papain-treated semen	1939:1973	bromelain- and papain-treated semen	1939:1973	Functional studies are needed to evaluate the sperm fertility rates of bromelain- and papain-treated semen for application in camel assisted reproductive technologies.
31405482	3	93	theme	liquefaction	673:684	arg1	treatments					686:695	the following liquefaction treatments	659:695	the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain	659:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	93	theme	liquefaction	673:684	arg1	bromelain					746:754	5 U/mL bromelain	739:754	5 U/mL bromelain	739:754	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	93	theme	liquefaction	673:684	arg1	papain					729:734	0.1 mg/mL papain	719:734	0.1 mg/mL papain	719:734	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	3	93	theme	liquefaction	673:684	arg1	control					698:704	control	698:704	control (untreated)	698:716	A portion of each raw ejaculate was evaluated for sperm physical and morphological traits, whereas the other portion was divided into three aliquots assigned for the following liquefaction treatments: control (untreated), 0.1 mg/mL papain or 5 U/mL bromelain.
31405482	4	94	theme	Tris-lactose	787:798	arg1	diluent					800:806	Tris-lactose diluent	787:806	Tris-lactose diluent containing the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation	787:911	All samples were diluted with Tris-lactose diluent containing the anti-enzyme E-64 to neutralize both proteases before being processed for cryopreservation.
31405482	9	95	theme	glycan	1676:1681	arg1	content					1683:1689	the N-linked glycan content	1663:1689	the N-linked glycan content of the entire sperm surface	1663:1717	Results from the glycan analysis indicated that both proteases did not affect the N-linked glycan content of the entire sperm surface, whereas the treatment with proteases induced little change in N-acetylgalactosamine and fucose terminating glycans in the tail region of the sperm.
30153274	0	0	theme	Toll-like	90:98	arg1	activation					130:139	Toll-like receptor 4-mediated host cell activation	90:139	Toll-like receptor 4-mediated host cell activation	90:139	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	3	1	with	coculture	603:611	arg1	cells					623:627	host cells	618:627	host cells	618:627	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	4	2	from	release	754:760	arg1	coculture					736:744	coculture	736:744	coculture	736:744	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	10	3	theme	P.	1630:1631	arg1	gingivalis					1633:1642	P. gingivalis	1630:1642	P. gingivalis	1630:1642	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	9	4	theme	serum	1487:1491	arg1	resistance					1493:1502	serum resistance	1487:1502	serum resistance of P. gingivalis	1487:1519	Thus, this study suggests that OmpALPs Pgm6 and Pgm7 are important for serum resistance of P. gingivalis.
30153274	2	5	theme	gingivalis	457:466	arg1	infection					468:476	P. gingivalis infection	454:476	P. gingivalis infection	454:476	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	9	6	theme	gingivalis	1510:1519	arg1	resistance					1493:1502	serum resistance	1487:1502	serum resistance of P. gingivalis	1487:1519	Thus, this study suggests that OmpALPs Pgm6 and Pgm7 are important for serum resistance of P. gingivalis.
30153274	4	7	theme	strains	678:684	arg1	ability					646:652	Such an altered ability	630:652	Such an altered ability of the OmpALP-deficient strains	630:684	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	4	7	theme	strains	678:684	arg1	due					702:704	due	702:704	due	702:704	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	8	8	theme	OmpALP-deficient	1301:1316	arg1	strains					1318:1324	the OmpALP-deficient strains	1297:1324	the OmpALP-deficient strains	1297:1324	Of note, the sensitivity of the OmpALP-deficient strains to the bactericidal activity of human β-defensin 3 was increased as compared with the WT.
30153274	1	9	theme	important	262:270	arg1	it					248:249	it	248:249	it	248:249	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	1	9	theme	important	262:270	arg1	pathogen					284:291	an important periodontal pathogen	259:291	an important periodontal pathogen	259:291	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	0	10	theme	4-mediated	109:118	arg1	activation					130:139	Toll-like receptor 4-mediated host cell activation	90:139	Toll-like receptor 4-mediated host cell activation	90:139	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	7	11	theme	proteinase	1241:1250	arg1	serum					1262:1266	proteinase K-treated serum	1241:1266	proteinase K-treated serum	1241:1266	The OmpALP-deficient strains did not survive in heat-inactivated serum, but they gained the ability to survive and grow in proteinase K-treated serum.
30153274	4	12	theme	impaired	715:722	arg1	survival					724:731	their impaired survival	709:731	their impaired survival in coculture	709:744	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	1	13	theme	periodontal	272:282	arg1	it					248:249	it	248:249	it	248:249	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	1	13	theme	periodontal	272:282	arg1	pathogen					284:291	an important periodontal pathogen	259:291	an important periodontal pathogen	259:291	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	0	14	theme	receptor	100:107	arg1	activation					130:139	Toll-like receptor 4-mediated host cell activation	90:139	Toll-like receptor 4-mediated host cell activation	90:139	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	2	15	from	roles	445:449	arg1	infection					468:476	P. gingivalis infection	454:476	P. gingivalis infection	454:476	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	10	16	theme	serum-containing	1665:1680	arg1	fluids					1702:1707	serum-containing gingival crevicular fluids	1665:1707	serum-containing gingival crevicular fluids	1665:1707	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	3	17	theme	OmpALP-deficient	520:535	arg1	strains					537:543	OmpALP-deficient strains	520:543	OmpALP-deficient strains of P. gingivalis	520:560	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	3	18	from	activity	591:598	arg1	coculture					603:611	coculture	603:611	coculture with host cells	603:627	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	0	19	theme	cell	125:128	arg1	activation					130:139	Toll-like receptor 4-mediated host cell activation	90:139	Toll-like receptor 4-mediated host cell activation	90:139	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	4	20	theme	Toll-like	808:816	arg1	receptor					818:825	Toll-like receptor 4	808:827	Toll-like receptor 4 (TLR4)	808:834	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	4	20	theme	Toll-like	808:816	arg1	TLR4					830:833	TLR4	830:833	TLR4	830:833	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	6	21	theme	normal	1035:1040	arg1	serum					1048:1052	90% normal human serum	1031:1052	90% normal human serum	1031:1052	The wild-type strain was able to grow in 90% normal human serum, while the OmpALP-deficient strains did not survive even at 5%.
30153274	2	22	theme	P.	294:295	arg1	gingivalis					297:306	P. gingivalis	294:306	P. gingivalis	294:306	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	7	23	theme	K-treated	1252:1260	arg1	serum					1262:1266	proteinase K-treated serum	1241:1266	proteinase K-treated serum	1241:1266	The OmpALP-deficient strains did not survive in heat-inactivated serum, but they gained the ability to survive and grow in proteinase K-treated serum.
30153274	4	24	theme	altered	638:644	arg1	ability					646:652	Such an altered ability	630:652	Such an altered ability of the OmpALP-deficient strains	630:684	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	4	24	theme	altered	638:644	arg1	due					702:704	due	702:704	due	702:704	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	0	25	theme	host	120:123	arg1	activation					130:139	Toll-like receptor 4-mediated host cell activation	90:139	Toll-like receptor 4-mediated host cell activation	90:139	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	10	26	theme	cell	1555:1558	arg1	destruction					1560:1570	bacterial cell destruction	1545:1570	bacterial cell destruction by serum and innate immune recognition by TLR4	1545:1617	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	4	27	from	survival	724:731	arg1	coculture					736:744	coculture	736:744	coculture	736:744	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	6	28	theme	wild-type	994:1002	arg1	able					1015:1018	able	1015:1018	able	1015:1018	The wild-type strain was able to grow in 90% normal human serum, while the OmpALP-deficient strains did not survive even at 5%.
30153274	6	28	theme	wild-type	994:1002	arg1	strain					1004:1009	The wild-type strain	990:1009	The wild-type strain	990:1009	The wild-type strain was able to grow in 90% normal human serum, while the OmpALP-deficient strains did not survive even at 5%.
30153274	6	29	theme	human	1042:1046	arg1	serum					1048:1052	90% normal human serum	1031:1052	90% normal human serum	1031:1052	The wild-type strain was able to grow in 90% normal human serum, while the OmpALP-deficient strains did not survive even at 5%.
30153274	6	30	theme	%	1033:1033	arg1	serum					1048:1052	90% normal human serum	1031:1052	90% normal human serum	1031:1052	The wild-type strain was able to grow in 90% normal human serum, while the OmpALP-deficient strains did not survive even at 5%.
30153274	1	31	contain	possesses	167:175	arg2	abilities					185:193	various abilities to evade and disrupt host immune responses	177:236	various abilities to evade and disrupt host immune responses	177:236	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	1	31	contain	possesses	167:175	arg1	gingivalis					156:165	Porphyromonas gingivalis	142:165	Porphyromonas gingivalis	142:165	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	2	32	theme	A	340:340	arg1	glycoproteins					407:419	major O-linked glycoproteins	392:419	major O-linked glycoproteins	392:419	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	32	theme	A	340:340	arg1	Pgm7					383:386	Pgm7	383:386	Pgm7	383:386	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	32	theme	A	340:340	arg1	OmpALPs					364:370	OmpALPs	364:370	OmpALPs	364:370	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	32	theme	A	340:340	arg1	Pgm6					374:377	Pgm6	374:377	Pgm6	374:377	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	32	theme	A	340:340	arg1	proteins					354:361	outer membrane protein A (OmpA)-like proteins	317:361	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	6	33	theme	90	1031:1032	arg1	%					1033:1033	%	1033:1033	%	1033:1033	The wild-type strain was able to grow in 90% normal human serum, while the OmpALP-deficient strains did not survive even at 5%.
30153274	0	34	theme	OmpA-like	0:8	arg1	proteins					10:17	OmpA-like proteins	0:17	OmpA-like proteins of Porphyromonas gingivalis	0:45	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	2	35	theme	protein	332:338	arg1	OmpA					343:346	OmpA	343:346	OmpA	343:346	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	35	theme	protein	332:338	arg1	A					340:340	outer membrane protein A	317:340	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	1	36	theme	host	216:219	arg1	responses					228:236	host immune responses	216:236	host immune responses	216:236	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	0	37	theme	Porphyromonas	22:34	arg1	gingivalis					36:45	Porphyromonas gingivalis	22:45	Porphyromonas gingivalis	22:45	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	5	38	theme	bacterial	972:980	arg1	medium					982:987	the bacterial medium	968:987	the bacterial medium	968:987	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	8	39	theme	bactericidal	1333:1344	arg1	activity					1346:1353	the bactericidal activity	1329:1353	the bactericidal activity of human β-defensin 3	1329:1375	Of note, the sensitivity of the OmpALP-deficient strains to the bactericidal activity of human β-defensin 3 was increased as compared with the WT.
30153274	2	40	theme	membrane	323:330	arg1	OmpA					343:346	OmpA	343:346	OmpA	343:346	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	40	theme	membrane	323:330	arg1	A					340:340	outer membrane protein A	317:340	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	4	41	theme	bacterial	779:787	arg1	cells					789:793	dead bacterial cells	774:793	dead bacterial cells	774:793	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	1	42	theme	immune	221:226	arg1	responses					228:236	host immune responses	216:236	host immune responses	216:236	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	3	43	theme	gingivalis	551:560	arg1	strains					537:543	OmpALP-deficient strains	520:543	OmpALP-deficient strains of P. gingivalis	520:560	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	2	44	theme	outer	317:321	arg1	OmpA					343:346	OmpA	343:346	OmpA	343:346	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	44	theme	outer	317:321	arg1	A					340:340	outer membrane protein A	317:340	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	45	theme	major	392:396	arg1	glycoproteins					407:419	major O-linked glycoproteins	392:419	major O-linked glycoproteins	392:419	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	45	theme	major	392:396	arg1	proteins					354:361	outer membrane protein A (OmpA)-like proteins	317:361	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	46	theme	P.	454:455	arg1	infection					468:476	P. gingivalis infection	454:476	P. gingivalis infection	454:476	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	3	47	theme	enhanced	570:577	arg1	activity					591:598	an enhanced stimulatory activity	567:598	an enhanced stimulatory activity in coculture with host cells	567:627	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	10	48	theme	immune	1592:1597	arg1	recognition					1599:1609	innate immune recognition	1585:1609	innate immune recognition	1585:1609	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	0	49	theme	gingivalis	36:45	arg1	proteins					10:17	OmpA-like proteins	0:17	OmpA-like proteins of Porphyromonas gingivalis	0:45	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	10	50	theme	bacterial	1545:1553	arg1	destruction					1560:1570	bacterial cell destruction	1545:1570	bacterial cell destruction by serum and innate immune recognition by TLR4	1545:1617	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	3	51	theme	host	618:621	arg1	cells					623:627	host cells	618:627	host cells	618:627	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	3	52	theme	stimulatory	579:589	arg1	activity					591:598	an enhanced stimulatory activity	567:598	an enhanced stimulatory activity in coculture with host cells	567:627	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	10	53	theme	subgingival	1713:1723	arg1	environments					1725:1736	subgingival environments	1713:1736	subgingival environments	1713:1736	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	0	54	theme	serum	61:65	arg1	resistance					67:76	serum resistance	61:76	serum resistance	61:76	OmpA-like proteins of Porphyromonas gingivalis contribute to serum resistance and prevent Toll-like receptor 4-mediated host cell activation.
30153274	5	55	theme	Further	837:843	arg1	analyses					845:852	Further analyses	837:852	Further analyses	837:852	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	4	56	from	cells	789:793	arg1	release					754:760	the release	750:760	the release of LPS from dead bacterial cells	750:793	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	4	56	from	cells	789:793	arg1	survival					724:731	their impaired survival	709:731	their impaired survival in coculture	709:744	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	2	57	theme	-like	348:352	arg1	glycoproteins					407:419	major O-linked glycoproteins	392:419	major O-linked glycoproteins	392:419	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	57	theme	-like	348:352	arg1	Pgm7					383:386	Pgm7	383:386	Pgm7	383:386	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	57	theme	-like	348:352	arg1	OmpALPs					364:370	OmpALPs	364:370	OmpALPs	364:370	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	57	theme	-like	348:352	arg1	Pgm6					374:377	Pgm6	374:377	Pgm6	374:377	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	57	theme	-like	348:352	arg1	proteins					354:361	outer membrane protein A (OmpA)-like proteins	317:361	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	58	theme	pathological	432:443	arg1	roles					445:449	their pathological roles	426:449	their pathological roles in P. gingivalis infection	426:476	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	8	59	theme	β-defensin	1364:1373	arg1	activity					1346:1353	the bactericidal activity	1329:1353	the bactericidal activity of human β-defensin 3	1329:1375	Of note, the sensitivity of the OmpALP-deficient strains to the bactericidal activity of human β-defensin 3 was increased as compared with the WT.
30153274	5	60	theme	OmpALP-deficient	872:887	arg1	inviable					902:909	inviable	902:909	inviable	902:909	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	5	60	theme	OmpALP-deficient	872:887	arg1	strains					889:895	the OmpALP-deficient strains	868:895	the OmpALP-deficient strains	868:895	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	10	61	theme	crevicular	1691:1700	arg1	fluids					1702:1707	serum-containing gingival crevicular fluids	1665:1707	serum-containing gingival crevicular fluids	1665:1707	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	3	62	theme	P.	548:549	arg1	gingivalis					551:560	P. gingivalis	548:560	P. gingivalis	548:560	Here, we report that OmpALP-deficient strains of P. gingivalis show an enhanced stimulatory activity in coculture with host cells.
30153274	8	63	theme	human	1358:1362	arg1	β-defensin					1364:1373	human β-defensin 3	1358:1375	human β-defensin 3	1358:1375	Of note, the sensitivity of the OmpALP-deficient strains to the bactericidal activity of human β-defensin 3 was increased as compared with the WT.
30153274	4	64	theme	dead	774:777	arg1	cells					789:793	dead bacterial cells	774:793	dead bacterial cells	774:793	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	1	65	theme	Porphyromonas	142:154	arg1	gingivalis					156:165	Porphyromonas gingivalis	142:165	Porphyromonas gingivalis	142:165	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
30153274	5	66	theme	serum-containing	914:929	arg1	media					931:935	serum-containing media	914:935	serum-containing media	914:935	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	2	67	link	O-linked	398:405	arg1	glycoproteins					407:419	major O-linked glycoproteins	392:419	major O-linked glycoproteins	392:419	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	67	link	O-linked	398:405	arg1	proteins					354:361	outer membrane protein A (OmpA)-like proteins	317:361	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	10	68	theme	gingival	1682:1689	arg1	fluids					1702:1707	serum-containing gingival crevicular fluids	1665:1707	serum-containing gingival crevicular fluids	1665:1707	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	10	69	theme	innate	1585:1590	arg1	recognition					1599:1609	innate immune recognition	1585:1609	innate immune recognition	1585:1609	These proteins prevent bacterial cell destruction by serum and innate immune recognition by TLR4; this way, P. gingivalis may adeptly colonize serum-containing gingival crevicular fluids and subgingival environments.
30153274	5	70	from	inviable	902:909	arg1	media					931:935	serum-containing media	914:935	serum-containing media	914:935	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	6	71	theme	OmpALP-deficient	1065:1080	arg1	strains					1082:1088	the OmpALP-deficient strains	1061:1088	the OmpALP-deficient strains	1061:1088	The wild-type strain was able to grow in 90% normal human serum, while the OmpALP-deficient strains did not survive even at 5%.
30153274	7	72	theme	heat-inactivated	1166:1181	arg1	serum					1183:1187	heat-inactivated serum	1166:1187	heat-inactivated serum	1166:1187	The OmpALP-deficient strains did not survive in heat-inactivated serum, but they gained the ability to survive and grow in proteinase K-treated serum.
30153274	8	73	theme	strains	1318:1324	arg1	sensitivity					1282:1292	the sensitivity	1278:1292	the sensitivity of the OmpALP-deficient strains to the bactericidal activity of human β-defensin 3	1278:1375	Of note, the sensitivity of the OmpALP-deficient strains to the bactericidal activity of human β-defensin 3 was increased as compared with the WT.
30153274	2	74	gly	glycoproteins	407:419	arg1	glycoproteins					407:419	major O-linked glycoproteins	392:419	major O-linked glycoproteins	392:419	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	74	gly	glycoproteins	407:419	arg1	proteins					354:361	outer membrane protein A (OmpA)-like proteins	317:361	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	75	theme	O-linked	398:405	arg1	glycoproteins					407:419	major O-linked glycoproteins	392:419	major O-linked glycoproteins	392:419	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	2	75	theme	O-linked	398:405	arg1	proteins					354:361	outer membrane protein A (OmpA)-like proteins	317:361	outer membrane protein A (OmpA)-like proteins (OmpALPs)	317:371	P. gingivalis produces outer membrane protein A (OmpA)-like proteins (OmpALPs), Pgm6 and Pgm7, as major O-linked glycoproteins, but their pathological roles in P. gingivalis infection are largely unknown.
30153274	4	76	theme	OmpALP-deficient	661:676	arg1	strains					678:684	the OmpALP-deficient strains	657:684	the OmpALP-deficient strains	657:684	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	5	77	from	media	931:935	arg1	inviable					902:909	inviable	902:909	inviable	902:909	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	5	77	from	media	931:935	arg1	strains					889:895	the OmpALP-deficient strains	868:895	the OmpALP-deficient strains	868:895	Further analyses revealed that the OmpALP-deficient strains were inviable in serum-containing media although they grew normally in the bacterial medium.
30153274	9	78	theme	P.	1507:1508	arg1	gingivalis					1510:1519	P. gingivalis	1507:1519	P. gingivalis	1507:1519	Thus, this study suggests that OmpALPs Pgm6 and Pgm7 are important for serum resistance of P. gingivalis.
30153274	7	79	theme	OmpALP-deficient	1122:1137	arg1	strains					1139:1145	The OmpALP-deficient strains	1118:1145	The OmpALP-deficient strains	1118:1145	The OmpALP-deficient strains did not survive in heat-inactivated serum, but they gained the ability to survive and grow in proteinase K-treated serum.
30153274	4	80	theme	LPS	765:767	arg1	release					754:760	the release	750:760	the release of LPS from dead bacterial cells	750:793	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	4	80	theme	LPS	765:767	arg1	survival					724:731	their impaired survival	709:731	their impaired survival in coculture	709:744	Such an altered ability of the OmpALP-deficient strains was found to be due to their impaired survival in coculture and the release of LPS from dead bacterial cells to stimulate Toll-like receptor 4 (TLR4).
30153274	1	81	theme	various	177:183	arg1	abilities					185:193	various abilities to evade and disrupt host immune responses	177:236	various abilities to evade and disrupt host immune responses	177:236	Porphyromonas gingivalis possesses various abilities to evade and disrupt host immune responses, by which it acts as an important periodontal pathogen.
31817562	9	0	theme	PD	2071:2072	arg1	patients					2074:2081	PD patients	2071:2081	PD patients	2071:2081	Whether such a strategy could be applied in the clinic to avoid ultrafiltration failure in PD patients remains to be investigated.
31817562	1	1	theme	peritoneal	289:298	arg1	PD					310:311	PD	310:311	PD	310:311	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	1	1	theme	peritoneal	289:298	arg1	dialysis					300:307	peritoneal dialysis	289:307	glucose-containing peritoneal dialysis (PD) solutions	270:322	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	3	2	theme	sodium-glucose	747:760	arg1	cotransporter-1					762:776	sodium-glucose cotransporter-1	747:776	sodium-glucose cotransporter-1	747:776	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	8	3	theme	human	1899:1903	arg1	cells					1928:1932	human peritoneal mesothelial cells	1899:1932	human peritoneal mesothelial cells	1899:1932	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	6	4	theme	actin	1555:1559	arg1	protein					1561:1567	α-smooth muscle actin protein	1539:1567	α-smooth muscle actin protein	1539:1567	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	8	5	theme	mesothelial	1916:1926	arg1	cells					1928:1932	human peritoneal mesothelial cells	1899:1932	human peritoneal mesothelial cells	1899:1932	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	6	6	theme	α-smooth	1539:1546	arg1	protein					1561:1567	α-smooth muscle actin protein	1539:1567	α-smooth muscle actin protein	1539:1567	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	7	7	theme	high-glucose-induced	1655:1674	arg1	pathways					1684:1691	all the high-glucose-induced harmful pathways	1647:1691	all the high-glucose-induced harmful pathways	1647:1691	High-glucose conditions increased glucose transporters, glucose influx, ROS, all the high-glucose-induced harmful pathways, TGF-β1 and IL-8, cell apoptosis, and MMT.
31817562	4	8	theme	diversion	952:960	arg1	inhibition					889:898	the inhibition	885:898	the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal)	885:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	1	9	theme	ultrafiltration	223:237	arg1	failure					239:245	ultrafiltration failure	223:245	ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions	223:322	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	1	9	theme	ultrafiltration	223:237	arg1	heel					341:344	the Achilles' heel	327:344	the Achilles' heel of PD method	327:357	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	4	10	theme	upstream	965:972	arg1	products					985:992	upstream glycolytic products	965:992	upstream glycolytic products	965:992	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	2	11	from	types	505:509	arg1	effect					388:393	the protective effect	373:393	the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types	373:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	4	12	theme	hexosamine	1115:1124	arg1	pathway					1126:1132	the hexosamine pathway	1111:1132	the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins)	1111:1198	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	4	13	dep	pathway	1126:1132	arg1	determined					1135:1144	determined	1135:1144	determined by O-linked β-N-acetyl glucosamine-modified proteins	1135:1197	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	4	14	theme	3-phosphate	918:928	arg1	dehydrogenase					930:942	glyceraldehyde 3-phosphate dehydrogenase	903:942	glyceraldehyde 3-phosphate dehydrogenase	903:942	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	3	15	theme	reactive	795:802	arg1	ROS					820:822	ROS	820:822	ROS	820:822	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	15	theme	reactive	795:802	arg1	species					811:817	reactive oxygen species	795:817	reactive oxygen species (ROS)	795:823	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	0	16	dep	Mesenchymal	176:186	arg1	to					173:174	to	173:174	to	173:174	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	0	17	theme	Mesenchymal	176:186	arg1	Transition					188:197	Mesothelial to Mesenchymal Transition	161:197	Mesothelial to Mesenchymal Transition	161:197	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	8	18	theme	high	1793:1796	arg1	alterations					1814:1824	the above high glucose-induced alterations	1783:1824	the above high glucose-induced alterations	1783:1824	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	4	19	theme	β-N-acetyl	1158:1167	arg1	proteins					1190:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	4	20	theme	synthesis	1052:1060	arg1	pathway					1062:1068	the lipid synthesis pathway	1042:1068	the lipid synthesis pathway (assessed by protein kinase C activity)	1042:1108	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	7	21	theme	glucose	1604:1610	arg1	transporters					1612:1623	glucose transporters	1604:1623	glucose transporters	1604:1623	High-glucose conditions increased glucose transporters, glucose influx, ROS, all the high-glucose-induced harmful pathways, TGF-β1 and IL-8, cell apoptosis, and MMT.
31817562	0	22	theme	Peritoneal	91:100	arg1	Cells					114:118	Human Peritoneal Mesothelial Cells	85:118	Human Peritoneal Mesothelial Cells	85:118	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	1	23	theme	method	352:357	arg1	failure					239:245	ultrafiltration failure	223:245	ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions	223:322	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	1	23	theme	method	352:357	arg1	heel					341:344	the Achilles' heel	327:344	the Achilles' heel of PD method	327:357	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	4	24	theme	products	985:992	arg1	dehydrogenase					930:942	glyceraldehyde 3-phosphate dehydrogenase	903:942	glyceraldehyde 3-phosphate dehydrogenase	903:942	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	4	24	theme	products	985:992	arg1	diversion					952:960	the diversion	948:960	the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal)	948:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	9	25	theme	ultrafiltration	2044:2058	arg1	failure					2060:2066	ultrafiltration failure	2044:2066	ultrafiltration failure	2044:2066	Whether such a strategy could be applied in the clinic to avoid ultrafiltration failure in PD patients remains to be investigated.
31817562	5	26	theme	growth	1354:1359	arg1	interleukin-8					1402:1414	the pro-inflammatory interleukin-8	1381:1414	the pro-inflammatory interleukin-8 (IL-8)	1381:1421	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	26	theme	growth	1354:1359	arg1	TGF-β1					1372:1377	TGF-β1	1372:1377	TGF-β1	1372:1377	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	26	theme	growth	1354:1359	arg1	factor-β1					1361:1369	the profibrotic transforming growth factor-β1	1325:1369	the profibrotic transforming growth factor-β1 (TGF-β1)	1325:1378	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	2	27	theme	control	406:412	arg1	GCN-2					434:438	GCN-2	434:438	GCN-2	434:438	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	2	27	theme	control	406:412	arg1	nonderepressible-2					414:431	general control nonderepressible-2	398:431	general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types	398:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	8	28	theme	GCN-2	1857:1861	arg1	kinase					1863:1868	GCN-2 kinase	1857:1868	GCN-2 kinase	1857:1868	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	2	29	theme	high-glucose	467:478	arg1	conditions					480:489	high-glucose conditions	467:489	high-glucose conditions	467:489	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	4	30	theme	glycation	1218:1226	arg1	products					1232:1239	the advanced glycation end products	1205:1239	the advanced glycation end products generation pathway (assessed by methylglyoxal)	1205:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	2	31	theme	activation	448:457	arg1	effect					388:393	the protective effect	373:393	the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types	373:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	4	32	theme	products	1232:1239	arg1	pathway					1252:1258	the advanced glycation end products generation pathway	1205:1258	the advanced glycation end products generation pathway (assessed by methylglyoxal)	1205:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	0	33	theme	General	14:20	arg1	Kinase					49:54	General Control Nonderepressible-2 Kinase	14:54	General Control Nonderepressible-2 Kinase	14:54	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	1	34	theme	solutions	314:322	arg1	toxicity					258:265	the toxicity	254:265	the toxicity of glucose-containing peritoneal dialysis (PD) solutions	254:322	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	7	35	theme	harmful	1676:1682	arg1	pathways					1684:1691	all the high-glucose-induced harmful pathways	1647:1691	all the high-glucose-induced harmful pathways	1647:1691	High-glucose conditions increased glucose transporters, glucose influx, ROS, all the high-glucose-induced harmful pathways, TGF-β1 and IL-8, cell apoptosis, and MMT.
31817562	2	36	theme	cell	500:503	arg1	types					505:509	other cell types	494:509	other cell types	494:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	8	37	from	glucotoxicity	1882:1894	arg1	cells					1928:1932	human peritoneal mesothelial cells	1899:1932	human peritoneal mesothelial cells	1899:1932	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	5	38	theme	profibrotic	1329:1339	arg1	interleukin-8					1402:1414	the pro-inflammatory interleukin-8	1381:1414	the pro-inflammatory interleukin-8 (IL-8)	1381:1421	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	38	theme	profibrotic	1329:1339	arg1	TGF-β1					1372:1377	TGF-β1	1372:1377	TGF-β1	1372:1377	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	38	theme	profibrotic	1329:1339	arg1	factor-β1					1361:1369	the profibrotic transforming growth factor-β1	1325:1369	the profibrotic transforming growth factor-β1 (TGF-β1)	1325:1378	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	6	39	theme	Cell	1424:1427	arg1	apoptosis					1429:1437	Cell apoptosis	1424:1437	Cell apoptosis	1424:1437	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	0	40	theme	Nonderepressible-2	30:47	arg1	Kinase					49:54	General Control Nonderepressible-2 Kinase	14:54	General Control Nonderepressible-2 Kinase	14:54	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	4	41	theme	C	1098:1098	arg1	activity					1100:1107	protein kinase C activity	1083:1107	protein kinase C activity	1083:1107	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	3	42	theme	glucose	697:703	arg1	transporter-1					705:717	glucose transporter-1	697:717	glucose transporter-1	697:717	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	4	43	link	O-linked	1149:1156	arg1	proteins					1190:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	6	44	dep	mesenchymal	1493:1503	arg1	to					1490:1491	to	1490:1491	to	1490:1491	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	3	45	theme	intervention	681:692	arg1	impact					666:671	the impact	662:671	the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity	662:868	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	2	46	theme	protective	377:386	arg1	effect					388:393	the protective effect	373:393	the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types	373:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	2	47	theme	mesothelial	569:579	arg1	cells					581:585	human peritoneal mesothelial cells	552:585	human peritoneal mesothelial cells	552:585	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	1	48	theme	glucose-containing	270:287	arg1	solutions					314:322	glucose-containing peritoneal dialysis (PD) solutions	270:322	glucose-containing peritoneal dialysis (PD) solutions	270:322	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	4	49	theme	protein	1083:1089	arg1	activity					1100:1107	protein kinase C activity	1083:1107	protein kinase C activity	1083:1107	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	8	50	theme	peritoneal	1905:1914	arg1	cells					1928:1932	human peritoneal mesothelial cells	1899:1932	human peritoneal mesothelial cells	1899:1932	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	4	51	dep	pathway	1252:1258	arg1	assessed					1261:1268	assessed	1261:1268	assessed by methylglyoxal	1261:1285	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	1	52	theme	dialysis	300:307	arg1	solutions					314:322	glucose-containing peritoneal dialysis (PD) solutions	270:322	glucose-containing peritoneal dialysis (PD) solutions	270:322	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	3	53	from	impact	666:671	arg1	cotransporter-1					762:776	sodium-glucose cotransporter-1	747:776	sodium-glucose cotransporter-1	747:776	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	53	from	impact	666:671	arg1	transporter-1					705:717	glucose transporter-1	697:717	glucose transporter-1	697:717	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	53	from	impact	666:671	arg1	species					811:817	reactive oxygen species	795:817	reactive oxygen species (ROS)	795:823	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	53	from	impact	666:671	arg1	events					834:839	the events	830:839	the events that result in glucotoxicity	830:868	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	53	from	impact	666:671	arg1	transporter-3					728:740	glucose transporter-3	720:740	glucose transporter-3	720:740	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	53	from	impact	666:671	arg1	influx					787:792	glucose influx	779:792	glucose influx	779:792	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	53	from	impact	666:671	arg1	ROS					820:822	ROS	820:822	ROS	820:822	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	4	54	dep	pathway	1062:1068	arg1	assessed					1071:1078	assessed	1071:1078	assessed by protein kinase C activity	1071:1107	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	6	55	theme	muscle	1548:1553	arg1	protein					1561:1567	α-smooth muscle actin protein	1539:1567	α-smooth muscle actin protein	1539:1567	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	4	56	theme	O-linked	1149:1156	arg1	proteins					1190:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	2	57	theme	peritoneal	558:567	arg1	cells					581:585	human peritoneal mesothelial cells	552:585	human peritoneal mesothelial cells	552:585	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	3	58	theme	glucose	779:785	arg1	influx					787:792	glucose influx	779:792	glucose influx	779:792	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	59	theme	GCN-2	601:605	arg1	kinase					607:612	GCN-2 kinase	601:612	GCN-2 kinase	601:612	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	7	60	theme	glucose	1626:1632	arg1	influx					1634:1639	glucose influx	1626:1639	glucose influx	1626:1639	High-glucose conditions increased glucose transporters, glucose influx, ROS, all the high-glucose-induced harmful pathways, TGF-β1 and IL-8, cell apoptosis, and MMT.
31817562	4	61	theme	glyceraldehyde	903:916	arg1	dehydrogenase					930:942	glyceraldehyde 3-phosphate dehydrogenase	903:942	glyceraldehyde 3-phosphate dehydrogenase	903:942	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	4	62	theme	advanced	1209:1216	arg1	products					1232:1239	the advanced glycation end products	1205:1239	the advanced glycation end products generation pathway (assessed by methylglyoxal)	1205:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	3	63	theme	oxygen	804:809	arg1	ROS					820:822	ROS	820:822	ROS	820:822	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	3	63	theme	oxygen	804:809	arg1	species					811:817	reactive oxygen species	795:817	reactive oxygen species (ROS)	795:823	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	4	64	dep	pathway	1008:1014	arg1	assessed					1017:1024	assessed	1017:1024	assessed by D-sorbitol	1017:1038	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	4	65	theme	dehydrogenase	930:942	arg1	inhibition					889:898	the inhibition	885:898	the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal)	885:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	4	66	theme	glucosamine-modified	1169:1188	arg1	proteins					1190:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	O-linked β-N-acetyl glucosamine-modified proteins	1149:1197	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	0	67	theme	Human	85:89	arg1	Cells					114:118	Human Peritoneal Mesothelial Cells	85:118	Human Peritoneal Mesothelial Cells	85:118	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	8	68	theme	above	1787:1791	arg1	alterations					1814:1824	the above high glucose-induced alterations	1783:1824	the above high glucose-induced alterations	1783:1824	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	4	69	theme	aldose	1001:1006	arg1	pathway					1008:1014	the aldose pathway	997:1014	the aldose pathway (assessed by D-sorbitol)	997:1039	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	2	70	from	activation	448:457	arg1	types					505:509	other cell types	494:509	other cell types	494:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	0	71	theme	Mesothelial	102:112	arg1	Cells					114:118	Human Peritoneal Mesothelial Cells	85:118	Human Peritoneal Mesothelial Cells	85:118	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	1	72	theme	PD	349:350	arg1	method					352:357	PD method	349:357	PD method	349:357	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	8	73	theme	glucose-induced	1798:1812	arg1	alterations					1814:1824	the above high glucose-induced alterations	1783:1824	the above high glucose-induced alterations	1783:1824	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	7	74	theme	High-glucose	1570:1581	arg1	conditions					1583:1592	High-glucose conditions	1570:1592	High-glucose conditions	1570:1592	High-glucose conditions increased glucose transporters, glucose influx, ROS, all the high-glucose-induced harmful pathways, TGF-β1 and IL-8, cell apoptosis, and MMT.
31817562	4	75	theme	glycolytic	974:983	arg1	products					985:992	upstream glycolytic products	965:992	upstream glycolytic products	965:992	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	0	76	from	Glucotoxicity	68:80	arg1	Cells					114:118	Human Peritoneal Mesothelial Cells	85:118	Human Peritoneal Mesothelial Cells	85:118	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	5	77	theme	transforming	1341:1352	arg1	interleukin-8					1402:1414	the pro-inflammatory interleukin-8	1381:1414	the pro-inflammatory interleukin-8 (IL-8)	1381:1421	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	77	theme	transforming	1341:1352	arg1	TGF-β1					1372:1377	TGF-β1	1372:1377	TGF-β1	1372:1377	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	77	theme	transforming	1341:1352	arg1	factor-β1					1361:1369	the profibrotic transforming growth factor-β1	1325:1369	the profibrotic transforming growth factor-β1 (TGF-β1)	1325:1378	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	7	78	theme	cell	1711:1714	arg1	apoptosis					1716:1724	cell apoptosis	1711:1724	cell apoptosis	1711:1724	High-glucose conditions increased glucose transporters, glucose influx, ROS, all the high-glucose-induced harmful pathways, TGF-β1 and IL-8, cell apoptosis, and MMT.
31817562	4	79	theme	end	1228:1230	arg1	products					1232:1239	the advanced glycation end products	1205:1239	the advanced glycation end products generation pathway (assessed by methylglyoxal)	1205:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	5	80	theme	factor-β1	1361:1369	arg1	production					1311:1320	the production	1307:1320	the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8)	1307:1421	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	2	81	theme	general	398:404	arg1	GCN-2					434:438	GCN-2	434:438	GCN-2	434:438	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	2	81	theme	general	398:404	arg1	nonderepressible-2					414:431	general control nonderepressible-2	398:431	general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types	398:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	6	82	theme	cleaved	1455:1461	arg1	caspase-3					1463:1471	cleaved caspase-3	1455:1471	cleaved caspase-3	1455:1471	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	2	83	theme	human	552:556	arg1	cells					581:585	human peritoneal mesothelial cells	552:585	human peritoneal mesothelial cells	552:585	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	4	84	theme	generation	1241:1250	arg1	pathway					1252:1258	the advanced glycation end products generation pathway	1205:1258	the advanced glycation end products generation pathway (assessed by methylglyoxal)	1205:1286	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	0	85	theme	Control	22:28	arg1	Kinase					49:54	General Control Nonderepressible-2 Kinase	14:54	General Control Nonderepressible-2 Kinase	14:54	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	8	86	theme	kinase	1863:1868	arg1	activation					1843:1852	activation	1843:1852	activation of GCN-2 kinase	1843:1868	Halofuginone and tryptophanol inhibited all of the above high glucose-induced alterations, indicating that activation of GCN-2 kinase ameliorates glucotoxicity in human peritoneal mesothelial cells, preserves their integrity, and prevents MMT.
31817562	2	87	theme	kinase	441:446	arg1	activation					448:457	general control nonderepressible-2 (GCN-2) kinase activation	398:457	general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types	398:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	0	88	theme	Kinase	49:54	arg1	Activation					0:9	Activation	0:9	Activation of General Control Nonderepressible-2 Kinase	0:54	Activation of General Control Nonderepressible-2 Kinase Ameliorates Glucotoxicity in Human Peritoneal Mesothelial Cells, Preserves Their Integrity, and Prevents Mesothelial to Mesenchymal Transition.
31817562	2	89	theme	other	494:498	arg1	types					505:509	other cell types	494:509	other cell types	494:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	5	90	theme	pro-inflammatory	1385:1400	arg1	interleukin-8					1402:1414	the pro-inflammatory interleukin-8	1381:1414	the pro-inflammatory interleukin-8 (IL-8)	1381:1421	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	90	theme	pro-inflammatory	1385:1400	arg1	factor-β1					1361:1369	the profibrotic transforming growth factor-β1	1325:1369	the profibrotic transforming growth factor-β1 (TGF-β1)	1325:1378	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	5	90	theme	pro-inflammatory	1385:1400	arg1	IL-8					1417:1420	IL-8	1417:1420	IL-8	1417:1420	Then, we examined the production of the profibrotic transforming growth factor-β1 (TGF-β1), the pro-inflammatory interleukin-8 (IL-8).
31817562	2	91	theme	nonderepressible-2	414:431	arg1	activation					448:457	general control nonderepressible-2 (GCN-2) kinase activation	398:457	general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types	398:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	1	92	theme	Achilles	331:338	arg1	failure					239:245	ultrafiltration failure	223:245	ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions	223:322	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	1	92	theme	Achilles	331:338	arg1	heel					341:344	the Achilles' heel	327:344	the Achilles' heel of PD method	327:357	Along with infections, ultrafiltration failure due to the toxicity of glucose-containing peritoneal dialysis (PD) solutions is the Achilles' heel of PD method.
31817562	2	93	from	effect	388:393	arg1	types					505:509	other cell types	494:509	other cell types	494:509	Triggered by the protective effect of general control nonderepressible-2 (GCN-2) kinase activation against high-glucose conditions in other cell types, we evaluated whether the same occurs in human peritoneal mesothelial cells.
31817562	4	94	theme	kinase	1091:1096	arg1	activity					1100:1107	protein kinase C activity	1083:1107	protein kinase C activity	1083:1107	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31817562	6	95	theme	mesenchymal	1493:1503	arg1	MMT					1517:1519	MMT	1517:1519	MMT	1517:1519	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	6	95	theme	mesenchymal	1493:1503	arg1	transition					1505:1514	mesothelial to mesenchymal transition	1478:1514	mesothelial to mesenchymal transition (MMT)	1478:1520	Cell apoptosis was assessed by cleaved caspase-3, and mesothelial to mesenchymal transition (MMT) was evaluated by α-smooth muscle actin protein.
31817562	3	96	theme	glucose	720:726	arg1	transporter-3					728:740	glucose transporter-3	720:740	glucose transporter-3	720:740	We activated GCN-2 kinase with halofuginone or tryptophanol, and assessed the impact of this intervention on glucose transporter-1, glucose transporter-3, and sodium-glucose cotransporter-1, glucose influx, reactive oxygen species (ROS), and the events that result in glucotoxicity.
31817562	4	97	theme	lipid	1046:1050	arg1	pathway					1062:1068	the lipid synthesis pathway	1042:1068	the lipid synthesis pathway (assessed by protein kinase C activity)	1042:1108	These involve the inhibition of glyceraldehyde 3-phosphate dehydrogenase and the diversion of upstream glycolytic products to the aldose pathway (assessed by D-sorbitol), the lipid synthesis pathway (assessed by protein kinase C activity), the hexosamine pathway (determined by O-linked β-N-acetyl glucosamine-modified proteins), and the advanced glycation end products generation pathway (assessed by methylglyoxal).
31628985	0	0	theme	tetratricopeptide	70:86	arg1	domain					105:110	a tetratricopeptide (TPR) α-solenoid domain	68:110	a tetratricopeptide (TPR) α-solenoid domain	68:110	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	1	1	dep	superhelical	265:276	arg1	flexible					292:299	flexible	292:299	flexible	292:299	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	2	2	theme	cell	443:446	arg1	control					454:460	cell cycle control	443:460	cell cycle control	443:460	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	3	3	theme	substrate	632:640	arg1	proteins					642:649	substrate proteins	632:649	substrate proteins	632:649	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	6	4	theme	substrate	1192:1200	arg1	interaction					1202:1212	defective substrate interaction	1182:1212	defective substrate interaction	1182:1212	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	2	5	theme	cycle	448:452	arg1	control					454:460	cell cycle control	443:460	cell cycle control	443:460	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	8	6	with	design	1436:1441	arg1	properties					1487:1496	tailored biomechanical properties	1464:1496	tailored biomechanical properties	1464:1496	Our findings may not only help to explain the ID phenotype of the mutants, but also aid the design of TPR proteins with tailored biomechanical properties.
31628985	1	7	theme	α-helical	226:234	arg1	motifs					244:249	α-helical hairpin motifs	226:249	α-helical hairpin motifs	226:249	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	0	8	theme	TPR	89:91	arg1	domain					105:110	a tetratricopeptide (TPR) α-solenoid domain	68:110	a tetratricopeptide (TPR) α-solenoid domain	68:110	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	3	9	theme	proteins	642:649	arg1	range					623:627	a broad range	615:627	a broad range of substrate proteins	615:649	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	5	10	theme	ID-related	929:938	arg1	mutations					946:954	the ID-related local mutations	925:954	the ID-related local mutations	925:954	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	4	11	theme	human	708:712	arg1	OGT					714:716	human OGT	708:716	human OGT	708:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	4	12	theme	TPR	694:696	arg1	domain					698:703	the TPR domain	690:703	the TPR domain of human OGT	690:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	4	12	theme	TPR	694:696	arg1	OGT					714:716	human OGT	708:716	human OGT	708:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	1	13	theme	hairpin	236:242	arg1	motifs					244:249	α-helical hairpin motifs	226:249	α-helical hairpin motifs	226:249	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	6	14	theme	OGT	1117:1119	arg1	substrates					1121:1130	releasing OGT substrates	1107:1130	releasing OGT substrates	1107:1130	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	6	15	from	function	1083:1090	arg1	substrates					1121:1130	releasing OGT substrates	1107:1130	releasing OGT substrates	1107:1130	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	6	15	from	function	1083:1090	arg1	binding					1095:1101	binding	1095:1101	binding	1095:1101	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	1	16	theme	motifs	244:249	arg1	units					217:221	repetitive units	206:221	repetitive units of α-helical hairpin motifs	206:249	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	0	17	theme	α-solenoid	94:103	arg1	domain					105:110	a tetratricopeptide (TPR) α-solenoid domain	68:110	a tetratricopeptide (TPR) α-solenoid domain	68:110	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	2	18	theme	key	374:376	arg1	control					454:460	cell cycle control	443:460	cell cycle control	443:460	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	18	theme	key	374:376	arg1	modification					485:496	post-translational modification	466:496	post-translational modification	466:496	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	18	theme	key	374:376	arg1	roles					389:393	key functional roles	374:393	key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification	374:496	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	18	theme	key	374:376	arg1	folding					413:419	protein folding	405:419	protein folding	405:419	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	18	theme	key	374:376	arg1	trafficking					430:440	protein trafficking	422:440	protein trafficking	422:440	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	5	19	theme	extended	789:796	arg1	simulations					832:842	extended steered and equilibrium atomistic simulations	789:842	extended steered and equilibrium atomistic simulations	789:842	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	2	20	theme	post-translational	466:483	arg1	modification					485:496	post-translational modification	466:496	post-translational modification	466:496	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	3	21	link	O-linked	545:552	arg1	OGT					574:576	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	4	22	from	domain	698:703	arg1	number					654:659	A number	652:659	A number of single-point mutations in the TPR domain of human OGT	652:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	0	23	theme	Disease	0:6	arg1	mutations					29:37	Disease related single point mutations	0:37	Disease related single point mutations	0:37	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	2	24	theme	proteins	352:359	arg1	proteins					352:359	proteins	352:359	proteins	352:359	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	24	theme	proteins	352:359	arg1	variety					341:347	a wide variety	334:347	a wide variety of proteins	334:359	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	0	25	theme	related	8:14	arg1	mutations					29:37	Disease related single point mutations	0:37	Disease related single point mutations	0:37	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	8	26	theme	mutants	1410:1416	arg1	phenotype					1393:1401	the ID phenotype	1386:1401	the ID phenotype of the mutants	1386:1416	Our findings may not only help to explain the ID phenotype of the mutants, but also aid the design of TPR proteins with tailored biomechanical properties.
31628985	6	27	theme	biomechanics	1154:1165	arg1	changes					1139:1145	these changes	1133:1145	these changes of its biomechanics	1133:1165	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	7	28	theme	neutral	1228:1234	arg1	mutations					1236:1244	neutral mutations	1228:1244	neutral mutations	1228:1244	We find that neutral mutations in the human population, selected by analysis of the gnomAD database, do not incur these changes.
31628985	2	29	theme	protein	405:411	arg1	folding					413:419	protein folding	405:419	protein folding	405:419	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	4	30	theme	single-point	664:675	arg1	mutations					677:685	single-point mutations	664:685	single-point mutations in the TPR domain of human OGT	664:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	5	31	theme	steered	798:804	arg1	simulations					832:842	extended steered and equilibrium atomistic simulations	789:842	extended steered and equilibrium atomistic simulations	789:842	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	0	32	theme	point	23:27	arg1	mutations					29:37	Disease related single point mutations	0:37	Disease related single point mutations	0:37	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	7	33	theme	human	1253:1257	arg1	population					1259:1268	the human population	1249:1268	the human population	1249:1268	We find that neutral mutations in the human population, selected by analysis of the gnomAD database, do not incur these changes.
31628985	5	34	theme	OGT-TPR	862:868	arg1	nanospring					896:905	an elastic nanospring	885:905	an elastic nanospring	885:905	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	34	theme	OGT-TPR	862:868	arg1	domain					870:875	the OGT-TPR domain	858:875	the OGT-TPR domain	858:875	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	34	theme	OGT-TPR	862:868	arg1	dynamics					988:995	the global dynamics	977:995	the global dynamics of the TPR domain	977:1013	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	7	35	theme	gnomAD	1299:1304	arg1	database					1306:1313	the gnomAD database	1295:1313	the gnomAD database	1295:1313	We find that neutral mutations in the human population, selected by analysis of the gnomAD database, do not incur these changes.
31628985	4	36	theme	Intellectual	756:767	arg1	ID					781:782	ID	781:782	ID	781:782	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	4	36	theme	Intellectual	756:767	arg1	Disability					769:778	the disease Intellectual Disability	744:778	the disease Intellectual Disability (ID)	744:783	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	2	37	theme	functional	378:387	arg1	control					454:460	cell cycle control	443:460	cell cycle control	443:460	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	37	theme	functional	378:387	arg1	modification					485:496	post-translational modification	466:496	post-translational modification	466:496	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	37	theme	functional	378:387	arg1	roles					389:393	key functional roles	374:393	key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification	374:496	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	37	theme	functional	378:387	arg1	folding					413:419	protein folding	405:419	protein folding	405:419	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	37	theme	functional	378:387	arg1	trafficking					430:440	protein trafficking	422:440	protein trafficking	422:440	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	0	38	theme	single	16:21	arg1	mutations					29:37	Disease related single point mutations	0:37	Disease related single point mutations	0:37	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	0	39	theme	domain	105:110	arg1	dynamics					56:63	the global dynamics	45:63	the global dynamics of a tetratricopeptide (TPR) α-solenoid domain	45:110	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	3	40	theme	TPR	520:522	arg1	OGT					574:576	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	3	40	theme	TPR	520:522	arg1	domain					524:529	the TPR domain	516:529	the TPR domain	516:529	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	1	41	theme	α-solenoid	176:185	arg1	proteins					187:194	α-solenoid proteins	176:194	α-solenoid proteins	176:194	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	1	42	theme	superhelical	265:276	arg1	structures					301:310	superhelical, often highly flexible structures	265:310	superhelical, often highly flexible structures	265:310	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	3	43	theme	O-linked	545:552	arg1	OGT					574:576	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	1	44	theme	proteins	187:194	arg1	class					167:171	the class	163:171	the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures	163:310	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	5	45	theme	TPR	1004:1006	arg1	domain					1008:1013	the TPR domain	1000:1013	the TPR domain	1000:1013	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	3	46	theme	GlcNAc-transferase	554:571	arg1	OGT					574:576	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	0	47	theme	global	49:54	arg1	dynamics					56:63	the global dynamics	45:63	the global dynamics of a tetratricopeptide (TPR) α-solenoid domain	45:110	Disease related single point mutations alter the global dynamics of a tetratricopeptide (TPR) α-solenoid domain.
31628985	5	48	theme	atomistic	822:830	arg1	simulations					832:842	extended steered and equilibrium atomistic simulations	789:842	extended steered and equilibrium atomistic simulations	789:842	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	49	theme	domain	1008:1013	arg1	nanospring					896:905	an elastic nanospring	885:905	an elastic nanospring	885:905	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	49	theme	domain	1008:1013	arg1	domain					870:875	the OGT-TPR domain	858:875	the OGT-TPR domain	858:875	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	49	theme	domain	1008:1013	arg1	dynamics					988:995	the global dynamics	977:995	the global dynamics of the TPR domain	977:1013	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	6	50	theme	nanospring	1026:1035	arg1	key					1072:1074	key	1072:1074	key	1072:1074	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	6	50	theme	nanospring	1026:1035	arg1	character					1037:1045	the nanospring character	1022:1045	the nanospring character of the OGT-TPR domain	1022:1067	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	6	51	theme	OGT-TPR	1054:1060	arg1	domain					1062:1067	the OGT-TPR domain	1050:1067	the OGT-TPR domain	1050:1067	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	8	52	theme	ID	1390:1391	arg1	phenotype					1393:1401	the ID phenotype	1386:1401	the ID phenotype of the mutants	1386:1416	Our findings may not only help to explain the ID phenotype of the mutants, but also aid the design of TPR proteins with tailored biomechanical properties.
31628985	8	53	theme	proteins	1450:1457	arg1	design					1436:1441	the design	1432:1441	the design of TPR proteins with tailored biomechanical properties	1432:1496	Our findings may not only help to explain the ID phenotype of the mutants, but also aid the design of TPR proteins with tailored biomechanical properties.
31628985	3	54	theme	range	623:627	arg1	O-GlcNAcylation					596:610	O-GlcNAcylation	596:610	O-GlcNAcylation of a broad range of substrate proteins	596:649	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	3	55	theme	enzyme	538:543	arg1	OGT					574:576	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	2	56	theme	TPR	313:315	arg1	domains					317:323	TPR domains	313:323	TPR domains	313:323	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	4	57	from	mutations	677:685	arg1	domain					698:703	the TPR domain	690:703	the TPR domain of human OGT	690:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	4	57	from	mutations	677:685	arg1	OGT					714:716	human OGT	708:716	human OGT	708:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	8	58	theme	TPR	1446:1448	arg1	proteins					1450:1457	TPR proteins	1446:1457	TPR proteins	1446:1457	Our findings may not only help to explain the ID phenotype of the mutants, but also aid the design of TPR proteins with tailored biomechanical properties.
31628985	5	59	theme	local	940:944	arg1	mutations					946:954	the ID-related local mutations	925:954	the ID-related local mutations	925:954	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	4	60	theme	disease	748:754	arg1	ID					781:782	ID	781:782	ID	781:782	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	4	60	theme	disease	748:754	arg1	Disability					769:778	the disease Intellectual Disability	744:778	the disease Intellectual Disability (ID)	744:783	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	1	61	theme	Tetratricopeptide	113:129	arg1	TPR					139:141	TPR	139:141	TPR	139:141	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	1	61	theme	Tetratricopeptide	113:129	arg1	repeat					131:136	Tetratricopeptide repeat	113:136	Tetratricopeptide repeat (TPR) proteins	113:151	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	7	62	theme	database	1306:1313	arg1	analysis					1283:1290	analysis	1283:1290	analysis of the gnomAD database	1283:1313	We find that neutral mutations in the human population, selected by analysis of the gnomAD database, do not incur these changes.
31628985	4	63	theme	OGT	714:716	arg1	domain					698:703	the TPR domain	690:703	the TPR domain of human OGT	690:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	4	63	theme	OGT	714:716	arg1	OGT					714:716	human OGT	708:716	human OGT	708:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	5	64	theme	global	981:986	arg1	nanospring					896:905	an elastic nanospring	885:905	an elastic nanospring	885:905	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	64	theme	global	981:986	arg1	domain					870:875	the OGT-TPR domain	858:875	the OGT-TPR domain	858:875	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	64	theme	global	981:986	arg1	dynamics					988:995	the global dynamics	977:995	the global dynamics of the TPR domain	977:1013	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	65	theme	elastic	888:894	arg1	nanospring					896:905	an elastic nanospring	885:905	an elastic nanospring	885:905	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	65	theme	elastic	888:894	arg1	domain					870:875	the OGT-TPR domain	858:875	the OGT-TPR domain	858:875	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	5	65	theme	elastic	888:894	arg1	dynamics					988:995	the global dynamics	977:995	the global dynamics of the TPR domain	977:1013	By extended steered and equilibrium atomistic simulations, we show that the OGT-TPR domain acts as an elastic nanospring, and that each of the ID-related local mutations substantially affect the global dynamics of the TPR domain.
31628985	1	66	theme	repeat	131:136	arg1	proteins					144:151	Tetratricopeptide repeat (TPR) proteins	113:151	Tetratricopeptide repeat (TPR) proteins	113:151	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	3	67	from	domain	524:529	arg1	look					508:511	look	508:511	look	508:511	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	4	68	theme	mutations	677:685	arg1	number					654:659	A number	652:659	A number of single-point mutations in the TPR domain of human OGT	652:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	3	69	theme	broad	617:621	arg1	range					623:627	a broad range	615:627	a broad range of substrate proteins	615:649	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	6	70	theme	releasing	1107:1115	arg1	substrates					1121:1130	releasing OGT substrates	1107:1130	releasing OGT substrates	1107:1130	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	7	71	from	mutations	1236:1244	arg1	population					1259:1268	the human population	1249:1268	the human population	1249:1268	We find that neutral mutations in the human population, selected by analysis of the gnomAD database, do not incur these changes.
31628985	2	72	theme	wide	336:339	arg1	proteins					352:359	proteins	352:359	proteins	352:359	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	2	72	theme	wide	336:339	arg1	variety					341:347	a wide variety	334:347	a wide variety of proteins	334:359	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	4	73	from	number	654:659	arg1	domain					698:703	the TPR domain	690:703	the TPR domain of human OGT	690:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	4	73	from	number	654:659	arg1	OGT					714:716	human OGT	708:716	human OGT	708:716	A number of single-point mutations in the TPR domain of human OGT have been associated with the disease Intellectual Disability (ID).
31628985	1	74	theme	repetitive	206:215	arg1	units					217:221	repetitive units	206:221	repetitive units of α-helical hairpin motifs	206:249	Tetratricopeptide repeat (TPR) proteins belong to the class of α-solenoid proteins, in which repetitive units of α-helical hairpin motifs stack to form superhelical, often highly flexible structures.
31628985	2	75	theme	protein	422:428	arg1	trafficking					430:440	protein trafficking	422:440	protein trafficking	422:440	TPR domains occur in a wide variety of proteins, and perform key functional roles including protein folding, protein trafficking, cell cycle control and post-translational modification.
31628985	6	76	theme	domain	1062:1067	arg1	key					1072:1074	key	1072:1074	key	1072:1074	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	6	76	theme	domain	1062:1067	arg1	character					1037:1045	the nanospring character	1022:1045	the nanospring character of the OGT-TPR domain	1022:1067	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	3	77	theme	OGT	574:576	arg1	OGT					574:576	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	the enzyme O-linked GlcNAc-transferase (OGT)	534:577	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	3	77	theme	OGT	574:576	arg1	domain					524:529	the TPR domain	516:529	the TPR domain	516:529	Here, we look at the TPR domain of the enzyme O-linked GlcNAc-transferase (OGT), which catalyses O-GlcNAcylation of a broad range of substrate proteins.
31628985	8	78	theme	tailored	1464:1471	arg1	properties					1487:1496	tailored biomechanical properties	1464:1496	tailored biomechanical properties	1464:1496	Our findings may not only help to explain the ID phenotype of the mutants, but also aid the design of TPR proteins with tailored biomechanical properties.
31628985	6	79	theme	defective	1182:1190	arg1	interaction					1202:1212	defective substrate interaction	1182:1212	defective substrate interaction	1182:1212	Since the nanospring character of the OGT-TPR domain is key to its function in binding and releasing OGT substrates, these changes of its biomechanics likely lead to defective substrate interaction.
31628985	8	80	theme	biomechanical	1473:1485	arg1	properties					1487:1496	tailored biomechanical properties	1464:1496	tailored biomechanical properties	1464:1496	Our findings may not only help to explain the ID phenotype of the mutants, but also aid the design of TPR proteins with tailored biomechanical properties.
31231498	6	0	theme	transferase	957:967	arg1	expression					839:848	the gene expression	830:848	the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT)	830:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	0	theme	transferase	957:967	arg1	level					778:782	the level	774:782	the level of advanced glycation end products (AGEs)	774:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	9	1	contain	had	1400:1402	arg1	Serum					1359:1363	Serum HbA1c and liver AGE concentrations	1359:1398	Serum	1359:1363	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	9	1	contain	had	1400:1402	arg2	reduction					1431:1439	a slight but insignificant reduction	1404:1439	a slight but insignificant reduction	1404:1439	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	9	1	contain	had	1400:1402	arg1	concentrations					1385:1398	liver AGE concentrations	1375:1398	liver AGE concentrations	1375:1398	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	6	2	link	O-linked	928:935	arg1	OGT					970:972	OGT	970:972	OGT	970:972	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	2	link	O-linked	928:935	arg1	transferase					957:967	O-linked N-acetylglucosamine transferase	928:967	O-linked N-acetylglucosamine transferase (OGT)	928:973	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	2	3	theme	MATERIALS	305:313	arg1	rats					359:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group).
31231498	1	4	theme	genes	211:215	arg1	metabolism					161:170	glucose metabolism	153:170	glucose metabolism	153:170	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	1	4	theme	genes	211:215	arg1	expression					188:197	the expression	184:197	the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats	184:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	6	5	theme	products	810:817	arg1	expression					839:848	the gene expression	830:848	the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT)	830:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	5	theme	products	810:817	arg1	level					778:782	the level	774:782	the level of advanced glycation end products (AGEs)	774:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	6	theme	glycation	796:804	arg1	AGEs					820:823	AGEs	820:823	AGEs	820:823	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	6	theme	glycation	796:804	arg1	products					810:817	advanced glycation end products	787:817	advanced glycation end products (AGEs)	787:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	3	7	theme	other	470:474	arg1	groups					480:485	the other two groups	466:485	the other two groups	466:485	The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes.
31231498	8	8	dep	increased	1258:1266	arg1	3.31±0.65					1324:1332	3.31±0.65	1324:1332	3.31±0.65	1324:1332	Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01).
31231498	8	8	dep	increased	1258:1266	arg1	2.15±0.79					1338:1346	2.15±0.79	1338:1346	2.15±0.79	1338:1346	Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01).
31231498	11	9	theme	diabetes	1654:1661	arg1	complications					1663:1675	diabetes complications	1654:1675	diabetes complications	1654:1675	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	1	10	from	development	233:243	arg1	tissue					280:285	liver tissue	274:285	liver tissue of diabetic rats	274:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	6	11	theme	cellular	857:864	arg1	AGER					876:879	AGER	876:879	AGER	876:879	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	11	theme	cellular	857:864	arg1	receptor					866:873	AGE cellular receptor	853:873	AGE cellular receptor (AGER)	853:880	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	10	12	theme	significant	1481:1491	arg1	decline					1493:1499	a significant decline	1479:1499	a significant decline	1479:1499	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	3	13	theme	streptozotocin	537:550	arg1	injection					515:523	an intraperitoneal injection	496:523	an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes	496:570	The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes.
31231498	6	14	theme	gene	834:837	arg1	expression					839:848	the gene expression	830:848	the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT)	830:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	7	15	from	increase	1090:1097	arg1	level					1109:1113	plasma level	1102:1113	plasma level of 25-hydroxycholecalciferol	1102:1142	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	7	16	theme	plasma	1102:1107	arg1	level					1109:1113	plasma level	1102:1113	plasma level of 25-hydroxycholecalciferol	1102:1142	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	9	17	theme	liver	1375:1379	arg1	concentrations					1385:1398	liver AGE concentrations	1375:1398	liver AGE concentrations	1375:1398	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	6	18	theme	glyoxalase-1	883:894	arg1	expression					839:848	the gene expression	830:848	the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT)	830:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	18	theme	glyoxalase-1	883:894	arg1	level					778:782	the level	774:782	the level of advanced glycation end products (AGEs)	774:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	1	19	theme	rats	299:302	arg1	tissue					280:285	liver tissue	274:285	liver tissue of diabetic rats	274:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	1	20	theme	vitamin	140:146	arg1	D					148:148	vitamin D	140:148	vitamin D	140:148	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	9	21	dep	Serum	1359:1363	arg1	HbA1c					1365:1369	HbA1c	1365:1369	HbA1c	1365:1369	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	11	22	theme	Vitamin	1611:1617	arg1	D					1619:1619	CONCLUSION Vitamin D	1600:1619	CONCLUSION Vitamin D	1600:1619	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	10	23	theme	gene	1517:1520	arg1	expression					1522:1531	gene expression	1517:1531	gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively)	1517:1597	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	2	24	dep	groups	397:402	arg1	rats					407:410	8 rats	405:410	8 rats in each group	405:424	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group).
31231498	0	25	from	pathways	30:37	arg1	liver					67:71	liver	67:71	liver	67:71	Vitamin D suppresses cellular pathways of diabetes complication in liver.
31231498	4	26	theme	IU/kg	666:670	arg1	injections					646:655	two injections	642:655	two injections of 20000 IU/kg	642:670	Groups were treated for four weeks either with placebo or vitamin D (two injections of 20000 IU/kg).
31231498	2	27	theme	Sprague-Dawley	344:357	arg1	rats					359:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group).
31231498	0	28	theme	Vitamin	0:6	arg1	D					8:8	Vitamin D	0:8	Vitamin D	0:8	Vitamin D suppresses cellular pathways of diabetes complication in liver.
31231498	7	29	theme	placebo-receiving	1201:1217	arg1	P=0.005					1234:1240	P=0.005	1234:1240	P=0.005	1234:1240	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	7	29	theme	placebo-receiving	1201:1217	arg1	rats					1228:1231	placebo-receiving diabetic rats	1201:1231	placebo-receiving diabetic rats (P=0.005)	1201:1241	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	10	30	dep	tissue	1558:1563	arg1	P=0.04					1566:1571	P=0.04	1566:1571	P=0.04	1566:1571	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	10	30	dep	tissue	1558:1563	arg1	P<0.001					1577:1583	P<0.001	1577:1583	P<0.001	1577:1583	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	9	31	theme	vitamin	1451:1457	arg1	intake					1461:1466	vitamin D intake	1451:1466	vitamin D intake	1451:1466	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	6	32	theme	reductase	912:920	arg1	expression					839:848	the gene expression	830:848	the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT)	830:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	32	theme	reductase	912:920	arg1	level					778:782	the level	774:782	the level of advanced glycation end products (AGEs)	774:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	7	33	theme	D	1052:1052	arg1	injection					1054:1062	Vitamin D injection	1044:1062	Vitamin D injection	1044:1062	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	11	34	theme	OGT	1766:1768	arg1	expression					1775:1784	OGT gene expression	1766:1784	OGT gene expression	1766:1784	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	5	35	theme	glucose	702:708	arg1	levels					692:697	serum levels	686:697	serum levels of glucose, insulin and HbA1c	686:727	Thereafter, serum levels of glucose, insulin and HbA1c were assessed.
31231498	1	36	theme	complications	257:269	arg1	development					233:243	the development	229:243	the development of diabetes complications in liver tissue of diabetic rats	229:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	4	37	dep	treated	585:591	arg1	injections					646:655	two injections	642:655	two injections of 20000 IU/kg	642:670	Groups were treated for four weeks either with placebo or vitamin D (two injections of 20000 IU/kg).
31231498	8	38	theme	vitamin	1283:1289	arg1	treatment					1293:1301	vitamin D treatment	1283:1301	vitamin D treatment	1283:1301	Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01).
31231498	3	39	theme	first	432:436	arg1	group					438:442	The first group	428:442	The first group	428:442	The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes.
31231498	5	40	theme	insulin	711:717	arg1	levels					692:697	serum levels	686:697	serum levels of glucose, insulin and HbA1c	686:727	Thereafter, serum levels of glucose, insulin and HbA1c were assessed.
31231498	1	41	theme	liver	274:278	arg1	tissue					280:285	liver tissue	274:285	liver tissue of diabetic rats	274:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	6	42	theme	glutamine/	979:988	arg1	GFAT					1029:1032	GFAT	1029:1032	GFAT	1029:1032	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	42	theme	glutamine/	979:988	arg1	aminotransferase					1011:1026	glutamine/ fructose-6-phosphate aminotransferase	979:1026	glutamine/ fructose-6-phosphate aminotransferase (GFAT)	979:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	8	43	theme	treatment	1293:1301	arg1	result					1273:1278	a result	1271:1278	a result of vitamin D treatment	1271:1301	Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01).
31231498	11	44	theme	blood	1699:1703	arg1	glucose					1705:1711	blood glucose	1699:1711	blood glucose	1699:1711	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	6	45	theme	Liver	744:748	arg1	tissue					750:755	Liver tissue	744:755	Liver tissue	744:755	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	7	46	theme	significant	1078:1088	arg1	increase					1090:1097	a significant increase	1076:1097	a significant increase	1076:1097	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	1	47	theme	key	207:209	arg1	genes					211:215	five key genes	202:215	five key genes involved in the development of diabetes complications in liver tissue of diabetic rats	202:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	11	48	dep	ameliorating	1641:1652	arg1	suppressing					1745:1755	suppressing	1745:1755	suppressing AGER and OGT gene expression in the liver	1745:1797	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	11	48	dep	ameliorating	1641:1652	arg1	improving					1689:1697	improving	1689:1697	improving blood glucose and insulin levels	1689:1730	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	6	49	theme	N-acetylglucosamine	937:955	arg1	OGT					970:972	OGT	970:972	OGT	970:972	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	49	theme	N-acetylglucosamine	937:955	arg1	transferase					957:967	O-linked N-acetylglucosamine transferase	928:967	O-linked N-acetylglucosamine transferase (OGT)	928:973	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	50	theme	end	806:808	arg1	AGEs					820:823	AGEs	820:823	AGEs	820:823	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	50	theme	end	806:808	arg1	products					810:817	advanced glycation end products	787:817	advanced glycation end products (AGEs)	787:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	1	51	theme	D	148:148	arg1	effect					130:135	the effect	126:135	the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats	126:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	0	52	theme	diabetes	42:49	arg1	complication					51:62	diabetes complication	42:62	diabetes complication	42:62	Vitamin D suppresses cellular pathways of diabetes complication in liver.
31231498	6	53	theme	advanced	787:794	arg1	AGEs					820:823	AGEs	820:823	AGEs	820:823	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	53	theme	advanced	787:794	arg1	products					810:817	advanced glycation end products	787:817	advanced glycation end products (AGEs)	787:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	3	54	theme	intraperitoneal	499:513	arg1	injection					515:523	an intraperitoneal injection	496:523	an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes	496:570	The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes.
31231498	1	55	theme	glucose	153:159	arg1	metabolism					161:170	glucose metabolism	153:170	glucose metabolism	153:170	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	6	56	theme	receptor	866:873	arg1	expression					839:848	the gene expression	830:848	the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT)	830:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	56	theme	receptor	866:873	arg1	level					778:782	the level	774:782	the level of advanced glycation end products (AGEs)	774:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	10	57	located	observed	1505:1512	arg2	decline					1493:1499	a significant decline	1479:1499	a significant decline	1479:1499	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	10	57	located	observed	1505:1512	arg1	expression					1522:1531	gene expression	1517:1531	gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively)	1517:1597	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	6	58	theme	AGE	853:855	arg1	AGER					876:879	AGER	876:879	AGER	876:879	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	58	theme	AGE	853:855	arg1	receptor					866:873	AGE cellular receptor	853:873	AGE cellular receptor (AGER)	853:880	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	59	theme	aminotransferase	1011:1026	arg1	expression					839:848	the gene expression	830:848	the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT)	830:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	59	theme	aminotransferase	1011:1026	arg1	level					778:782	the level	774:782	the level of advanced glycation end products (AGEs)	774:824	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	11	60	theme	insulin	1717:1723	arg1	levels					1725:1730	blood glucose and insulin levels	1699:1730	blood glucose and insulin levels	1699:1730	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	3	61	theme	mg/kg	531:535	arg1	streptozotocin					537:550	45 mg/kg streptozotocin	528:550	45 mg/kg streptozotocin	528:550	The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes.
31231498	1	62	theme	study	101:105	arg1	aim					89:91	The aim	85:91	The aim of this study	85:105	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	1	63	dep	OBJECTIVES	74:83	arg1	was					107:109	was	107:109	was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats	107:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	11	64	theme	CONCLUSION	1600:1609	arg1	D					1619:1619	CONCLUSION Vitamin D	1600:1619	CONCLUSION Vitamin D	1600:1619	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	5	65	theme	serum	686:690	arg1	levels					692:697	serum levels	686:697	serum levels of glucose, insulin and HbA1c	686:727	Thereafter, serum levels of glucose, insulin and HbA1c were assessed.
31231498	1	66	theme	diabetic	290:297	arg1	rats					299:302	diabetic rats	290:302	diabetic rats	290:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	9	67	theme	AGE	1381:1383	arg1	concentrations					1385:1398	liver AGE concentrations	1375:1398	liver AGE concentrations	1375:1398	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	2	68	from	rats	407:410	arg1	group					420:424	each group	415:424	each group	415:424	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group).
31231498	7	69	dep	RESULTS	1036:1042	arg1	resulted					1064:1071	resulted	1064:1071	resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005)	1064:1241	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	4	70	theme	vitamin	631:637	arg1	D					639:639	vitamin D	631:639	vitamin D	631:639	Groups were treated for four weeks either with placebo or vitamin D (two injections of 20000 IU/kg).
31231498	11	71	theme	glucose	1705:1711	arg1	levels					1725:1730	blood glucose and insulin levels	1699:1730	blood glucose and insulin levels	1699:1730	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	1	72	from	effect	130:135	arg1	metabolism					161:170	glucose metabolism	153:170	glucose metabolism	153:170	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	1	72	from	effect	130:135	arg1	expression					188:197	the expression	184:197	the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats	184:302	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	9	73	theme	slight	1406:1411	arg1	reduction					1431:1439	a slight but insignificant reduction	1404:1439	a slight but insignificant reduction	1404:1439	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	6	74	theme	O-linked	928:935	arg1	OGT					970:972	OGT	970:972	OGT	970:972	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	74	theme	O-linked	928:935	arg1	transferase					957:967	O-linked N-acetylglucosamine transferase	928:967	O-linked N-acetylglucosamine transferase (OGT)	928:973	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	7	75	theme	Vitamin	1044:1050	arg1	injection					1054:1062	Vitamin D injection	1044:1062	Vitamin D injection	1044:1062	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	9	76	theme	insignificant	1417:1429	arg1	reduction					1431:1439	a slight but insignificant reduction	1404:1439	a slight but insignificant reduction	1404:1439	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	8	77	theme	Insulin	1244:1250	arg1	level					1252:1256	Insulin level	1244:1256	Insulin level	1244:1256	Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01).
31231498	2	78	theme	male	339:342	arg1	rats					359:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group).
31231498	0	79	theme	cellular	21:28	arg1	pathways					30:37	cellular pathways	21:37	cellular pathways of diabetes complication in liver	21:71	Vitamin D suppresses cellular pathways of diabetes complication in liver.
31231498	5	80	theme	HbA1c	723:727	arg1	levels					692:697	serum levels	686:697	serum levels of glucose, insulin and HbA1c	686:727	Thereafter, serum levels of glucose, insulin and HbA1c were assessed.
31231498	10	81	theme	AGER	1536:1539	arg1	expression					1522:1531	gene expression	1517:1531	gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively)	1517:1597	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	1	82	theme	diabetes	248:255	arg1	complications					257:269	diabetes complications	248:269	diabetes complications	248:269	OBJECTIVES The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats.
31231498	9	83	theme	D	1459:1459	arg1	intake					1461:1466	vitamin D intake	1451:1466	vitamin D intake	1451:1466	Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake.
31231498	6	84	theme	aldose	905:910	arg1	reductase					912:920	aldose reductase	905:920	aldose reductase (AR)	905:925	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	84	theme	aldose	905:910	arg1	AR					923:924	AR	923:924	AR	923:924	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	7	85	theme	diabetic	1219:1226	arg1	P=0.005					1234:1240	P=0.005	1234:1240	P=0.005	1234:1240	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	7	85	theme	diabetic	1219:1226	arg1	rats					1228:1231	placebo-receiving diabetic rats	1201:1231	placebo-receiving diabetic rats (P=0.005)	1201:1241	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	11	86	theme	gene	1770:1773	arg1	expression					1775:1784	OGT gene expression	1766:1784	OGT gene expression	1766:1784	CONCLUSION Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.
31231498	0	87	theme	complication	51:62	arg1	pathways					30:37	cellular pathways	21:37	cellular pathways of diabetes complication in liver	21:71	Vitamin D suppresses cellular pathways of diabetes complication in liver.
31231498	8	88	dep	3.31±0.65	1324:1332	arg1	P=					1349:1350	P= 0.01	1349:1355	P= 0.01	1349:1355	Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01).
31231498	6	89	theme	fructose-6-phosphate	990:1009	arg1	GFAT					1029:1032	GFAT	1029:1032	GFAT	1029:1032	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	6	89	theme	fructose-6-phosphate	990:1009	arg1	aminotransferase					1011:1026	glutamine/ fructose-6-phosphate aminotransferase	979:1026	glutamine/ fructose-6-phosphate aminotransferase (GFAT)	979:1033	Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT).
31231498	10	90	theme	liver	1552:1556	arg1	tissue					1558:1563	liver tissue	1552:1563	liver tissue (P=0.04 and P<0.001 respectively)	1552:1597	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	8	91	theme	D	1291:1291	arg1	treatment					1293:1301	vitamin D treatment	1283:1301	vitamin D treatment	1283:1301	Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01).
31231498	10	92	theme	OGT	1545:1547	arg1	expression					1522:1531	gene expression	1517:1531	gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively)	1517:1597	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	4	93	dep	weeks	602:606	arg1	either					608:613	either	608:613	either	608:613	Groups were treated for four weeks either with placebo or vitamin D (two injections of 20000 IU/kg).
31231498	10	94	from	expression	1522:1531	arg1	tissue					1558:1563	liver tissue	1552:1563	liver tissue (P=0.04 and P<0.001 respectively)	1552:1597	Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively).
31231498	7	95	theme	25-hydroxycholecalciferol	1118:1142	arg1	level					1109:1113	plasma level	1102:1113	plasma level of 25-hydroxycholecalciferol	1102:1142	RESULTS Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005).
31231498	2	96	theme	METHODS	319:325	arg1	rats					359:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats	305:362	MATERIALS AND METHODS Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group).
31168022	4	0	theme	110	473:475	arg1	kDa					477:479	kDa	477:479	kDa	477:479	However, purification and identification of the 110 kDa GP was unsuccessful due to its low abundance.
31168022	13	1	theme	110	1821:1823	arg1	kDa					1825:1827	kDa	1825:1827	kDa	1825:1827	These findings suggest that desmocollin colocalizes with the 110 kDa GP and that growth inhibition induced by the MLS128 antibody may be mediated through a mechanism that involves desmocollin.
31168022	8	2	theme	110	964:966	arg1	kDa					968:970	kDa	968:970	kDa	968:970	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	10	3	theme	cell	1311:1314	arg1	membrane					1316:1323	the cell membrane	1307:1323	the cell membrane	1307:1323	Confocal microscopy demonstrated colocalization of the desmocollin-specific antibody with the MLS128 antibody on the cell membrane, suggesting that desmocollin may contain Tn-antigens recognized by MLS128.
31168022	10	4	theme	antibody	1270:1277	arg1	colocalization					1227:1240	colocalization	1227:1240	colocalization of the desmocollin-specific antibody with the MLS128 antibody	1227:1302	Confocal microscopy demonstrated colocalization of the desmocollin-specific antibody with the MLS128 antibody on the cell membrane, suggesting that desmocollin may contain Tn-antigens recognized by MLS128.
31168022	3	5	theme	cell	334:337	arg1	growth					339:344	cell growth	334:344	cell growth	334:344	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	12	6	dep	kDa	1644:1646	arg1	GP					1648:1649	GP	1648:1649	GP	1648:1649	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	12	6	dep	kDa	1644:1646	arg1	desmocollin					1655:1665	desmocollin	1655:1665	desmocollin	1655:1665	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	1	7	theme	diverse	148:154	arg1	form					156:159	a diverse form	146:159	a diverse form of post-translational modification	146:194	Protein glycosylation is a diverse form of post-translational modification.
31168022	1	7	theme	diverse	148:154	arg1	glycosylation					129:141	Protein glycosylation	121:141	Protein glycosylation	121:141	Protein glycosylation is a diverse form of post-translational modification.
31168022	7	8	theme	potential	870:878	arg1	sites					891:895	potential Tn-antigen sites	870:895	potential Tn-antigen sites	870:895	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	10	9	theme	desmocollin-specific	1249:1268	arg1	antibody					1270:1277	the desmocollin-specific antibody	1245:1277	the desmocollin-specific antibody	1245:1277	Confocal microscopy demonstrated colocalization of the desmocollin-specific antibody with the MLS128 antibody on the cell membrane, suggesting that desmocollin may contain Tn-antigens recognized by MLS128.
31168022	13	10	theme	growth	1841:1846	arg1	inhibition					1848:1857	growth inhibition	1841:1857	growth inhibition induced by the MLS128 antibody	1841:1888	These findings suggest that desmocollin colocalizes with the 110 kDa GP and that growth inhibition induced by the MLS128 antibody may be mediated through a mechanism that involves desmocollin.
31168022	4	11	theme	GP	481:482	arg1	identification					451:464	identification	451:464	identification	451:464	However, purification and identification of the 110 kDa GP was unsuccessful due to its low abundance.
31168022	4	11	theme	GP	481:482	arg1	purification					434:445	purification	434:445	purification	434:445	However, purification and identification of the 110 kDa GP was unsuccessful due to its low abundance.
31168022	5	12	theme	sophisticated	559:571	arg1	method					605:610	a highly sophisticated and sensitive mass spectrometry method	550:610	a highly sophisticated and sensitive mass spectrometry method	550:610	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	7	13	theme	Tn-antigen	880:889	arg1	sites					891:895	potential Tn-antigen sites	870:895	potential Tn-antigen sites	870:895	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	12	14	theme	N-glycosidase	1607:1619	arg1	digestion					1623:1631	N-glycosidase F digestion	1607:1631	N-glycosidase F digestion of the 110 kDa GP and desmocollin	1607:1665	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	3	15	theme	110	361:363	arg1	kDa					365:367	kDa	365:367	kDa	365:367	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	5	16	theme	gel	697:699	arg1	electrophoresis					701:715	two-dimensional gel electrophoresis	681:715	two-dimensional gel electrophoresis	681:715	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	9	17	theme	cells	1087:1091	arg1	microscopy					1067:1076	Immunofluorescence microscopy	1048:1076	Immunofluorescence microscopy of LS180 cells	1048:1091	Immunofluorescence microscopy of LS180 cells revealed that desmocollin is membrane-bound, while desmoglein is primarily localized in the cytosol.
31168022	0	18	theme	110	99:101	arg1	kDa					103:105	kDa	103:105	kDa	103:105	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	10	19	contain	contain	1358:1364	arg2	Tn-antigens					1366:1376	Tn-antigens	1366:1376	Tn-antigens recognized by MLS128	1366:1397	Confocal microscopy demonstrated colocalization of the desmocollin-specific antibody with the MLS128 antibody on the cell membrane, suggesting that desmocollin may contain Tn-antigens recognized by MLS128.
31168022	10	19	contain	contain	1358:1364	arg1	desmocollin					1342:1352	desmocollin	1342:1352	desmocollin	1342:1352	Confocal microscopy demonstrated colocalization of the desmocollin-specific antibody with the MLS128 antibody on the cell membrane, suggesting that desmocollin may contain Tn-antigens recognized by MLS128.
31168022	5	20	theme	mass	587:590	arg1	method					605:610	a highly sophisticated and sensitive mass spectrometry method	550:610	a highly sophisticated and sensitive mass spectrometry method	550:610	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	5	21	theme	sensitive	577:585	arg1	method					605:610	a highly sophisticated and sensitive mass spectrometry method	550:610	a highly sophisticated and sensitive mass spectrometry method	550:610	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	10	22	with	colocalization	1227:1240	arg1	antibody					1295:1302	the MLS128 antibody	1284:1302	the MLS128 antibody	1284:1302	Confocal microscopy demonstrated colocalization of the desmocollin-specific antibody with the MLS128 antibody on the cell membrane, suggesting that desmocollin may contain Tn-antigens recognized by MLS128.
31168022	1	23	theme	post-translational	164:181	arg1	modification					183:194	post-translational modification	164:194	post-translational modification	164:194	Protein glycosylation is a diverse form of post-translational modification.
31168022	3	24	theme	cancer	411:416	arg1	cells					418:422	LS180 and HT29 colon cancer cells	390:422	cells	418:422	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	11	25	theme	LS180	1413:1417	arg1	cells					1419:1423	LS180 cells	1413:1423	LS180 cells	1413:1423	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	0	26	theme	cancer	45:50	arg1	growth					57:62	colon cancer cell growth	39:62	colon cancer cell growth	39:62	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	5	27	theme	present	531:537	arg1	study					539:543	The present study	527:543	The present study	527:543	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	11	28	theme	desmocollin-specific	1478:1497	arg1	antibody					1499:1506	a desmocollin-specific antibody	1476:1506	a desmocollin-specific antibody	1476:1506	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	11	29	theme	cell	1518:1521	arg1	viability					1523:1531	cell viability	1518:1531	cell viability	1518:1531	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	0	30	theme	antibody-induced	7:22	arg1	suppression					24:34	MLS128 antibody-induced suppression	0:34	MLS128 antibody-induced suppression of colon cancer cell growth	0:62	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	7	31	theme	many	806:809	arg1	sites					891:895	potential Tn-antigen sites	870:895	potential Tn-antigen sites	870:895	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	7	31	theme	many	806:809	arg1	pI					862:863	pI	862:863	pI	862:863	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	7	31	theme	many	806:809	arg1	mass					856:859	molecular mass	846:859	molecular mass	846:859	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	7	31	theme	many	806:809	arg1	characteristics					819:833	many similar characteristics	806:833	many similar characteristics	806:833	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	3	32	gly	glycoprotein	369:380	arg1	GP					383:384	GP	383:384	GP	383:384	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	3	32	gly	glycoprotein	369:380	arg1	glycoprotein					369:380	a 110 kDa glycoprotein	359:380	a 110 kDa glycoprotein (GP)	359:385	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	5	33	theme	spectrometry	592:603	arg1	method					605:610	a highly sophisticated and sensitive mass spectrometry method	550:610	a highly sophisticated and sensitive mass spectrometry method	550:610	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	3	34	theme	HT29	400:403	arg1	cells					418:422	LS180 and HT29 colon cancer cells	390:422	cells	418:422	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	0	35	theme	MLS128	0:5	arg1	suppression					24:34	MLS128 antibody-induced suppression	0:34	MLS128 antibody-induced suppression of colon cancer cell growth	0:62	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	7	36	theme	similar	811:817	arg1	sites					891:895	potential Tn-antigen sites	870:895	potential Tn-antigen sites	870:895	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	7	36	theme	similar	811:817	arg1	pI					862:863	pI	862:863	pI	862:863	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	7	36	theme	similar	811:817	arg1	mass					856:859	molecular mass	846:859	molecular mass	846:859	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	7	36	theme	similar	811:817	arg1	characteristics					819:833	many similar characteristics	806:833	many similar characteristics	806:833	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	11	37	dep	cell	1581:1584	arg1	survival					1597:1604	survival	1597:1604	survival	1597:1604	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	11	37	dep	cell	1581:1584	arg1	growth					1586:1591	growth	1586:1591	growth	1586:1591	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	11	38	from	role	1556:1559	arg1	cell					1581:1584	cell growth and survival	1581:1604	cell growth and survival	1581:1604	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	7	39	theme	molecular	846:854	arg1	mass					856:859	molecular mass	846:859	molecular mass	846:859	Of these, desmocollin and desmoglein shared many similar characteristics, including molecular mass, pI, and potential Tn-antigen sites.
31168022	3	40	theme	colon	405:409	arg1	cells					418:422	LS180 and HT29 colon cancer cells	390:422	cells	418:422	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	3	41	theme	kDa	365:367	arg1	GP					383:384	GP	383:384	GP	383:384	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	3	41	theme	kDa	365:367	arg1	glycoprotein					369:380	a 110 kDa glycoprotein	359:380	a 110 kDa glycoprotein (GP)	359:385	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	4	42	theme	low	512:514	arg1	abundance					516:524	its low abundance	508:524	its low abundance	508:524	However, purification and identification of the 110 kDa GP was unsuccessful due to its low abundance.
31168022	5	43	theme	two-dimensional	681:695	arg1	electrophoresis					701:715	two-dimensional gel electrophoresis	681:715	two-dimensional gel electrophoresis	681:715	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	8	44	theme	Western	898:904	arg1	analyses					915:922	Western blotting analyses	898:922	Western blotting analyses of LS180 cell lysates	898:944	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	5	45	dep	proteins	624:631	arg1	separated					668:676	separated	668:676	separated by two-dimensional gel electrophoresis	668:715	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	5	45	dep	proteins	624:631	arg1	immunoprecipitated					633:650	immunoprecipitated	633:650	immunoprecipitated with MLS128	633:662	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	9	46	located	localized	1168:1176	arg2	desmoglein					1144:1153	desmoglein	1144:1153	desmoglein	1144:1153	Immunofluorescence microscopy of LS180 cells revealed that desmocollin is membrane-bound, while desmoglein is primarily localized in the cytosol.
31168022	9	46	located	localized	1168:1176	arg1	cytosol					1185:1191	the cytosol	1181:1191	the cytosol	1181:1191	Immunofluorescence microscopy of LS180 cells revealed that desmocollin is membrane-bound, while desmoglein is primarily localized in the cytosol.
31168022	0	47	theme	kDa	103:105	arg1	glycoprotein					107:118	a 110 kDa glycoprotein	97:118	a 110 kDa glycoprotein	97:118	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	11	48	with	Treatment	1400:1408	arg1	siRNA					1430:1434	siRNA	1430:1434	siRNA to knock down desmocollin expression or a desmocollin-specific antibody	1430:1506	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	12	49	theme	N-glycosylation	1713:1727	arg1	sites					1729:1733	N-glycosylation sites	1713:1733	N-glycosylation sites	1713:1733	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	8	50	theme	blotting	906:913	arg1	analyses					915:922	Western blotting analyses	898:922	Western blotting analyses of LS180 cell lysates	898:944	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	3	51	theme	LS180	390:394	arg1	cells					418:422	LS180 and HT29 colon cancer cells	390:422	cells	418:422	MLS128 mAb inhibited cell growth and bound to a 110 kDa glycoprotein (GP) in LS180 and HT29 colon cancer cells.
31168022	5	52	used	used	545:548	arg2	study					539:543	The present study	527:543	The present study	527:543	The present study used a highly sophisticated and sensitive mass spectrometry method to identify proteins immunoprecipitated with MLS128 and separated by two-dimensional gel electrophoresis.
31168022	1	53	theme	modification	183:194	arg1	form					156:159	a diverse form	146:159	a diverse form of post-translational modification	146:194	Protein glycosylation is a diverse form of post-translational modification.
31168022	1	53	theme	modification	183:194	arg1	glycosylation					129:141	Protein glycosylation	121:141	Protein glycosylation	121:141	Protein glycosylation is a diverse form of post-translational modification.
31168022	0	54	theme	colon	39:43	arg1	growth					57:62	colon cancer cell growth	39:62	colon cancer cell growth	39:62	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	12	55	theme	kDa	1644:1646	arg1	digestion					1623:1631	N-glycosidase F digestion	1607:1631	N-glycosidase F digestion of the 110 kDa GP and desmocollin	1607:1665	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	11	56	dep	down	1445:1448	arg1	expression					1462:1471	desmocollin expression	1450:1471	desmocollin expression	1450:1471	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	8	57	theme	cell	933:936	arg1	lysates					938:944	LS180 cell lysates	927:944	LS180 cell lysates	927:944	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	0	58	theme	growth	57:62	arg1	suppression					24:34	MLS128 antibody-induced suppression	0:34	MLS128 antibody-induced suppression of colon cancer cell growth	0:62	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	11	59	theme	desmocollin	1450:1460	arg1	expression					1462:1471	desmocollin expression	1450:1471	desmocollin expression	1450:1471	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	2	60	theme	O-linked	222:229	arg1	N-acetylgalactosamines					231:252	Two to three consecutive O-linked N-acetylgalactosamines	197:252	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens)	197:266	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens) are recognized by antibodies such as MLS128.
31168022	2	60	theme	O-linked	222:229	arg1	Tn-antigens					255:265	Tn-antigens	255:265	Tn-antigens	255:265	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens) are recognized by antibodies such as MLS128.
31168022	8	61	theme	LS180	927:931	arg1	lysates					938:944	LS180 cell lysates	927:944	LS180 cell lysates	927:944	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	0	62	theme	cell	52:55	arg1	growth					57:62	colon cancer cell growth	39:62	colon cancer cell growth	39:62	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	12	63	contain	contain	1705:1711	arg1	proteins					1696:1703	both proteins	1691:1703	both proteins	1691:1703	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	12	63	contain	contain	1705:1711	arg2	sites					1729:1733	N-glycosylation sites	1713:1733	N-glycosylation sites	1713:1733	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	2	64	theme	consecutive	210:220	arg1	N-acetylgalactosamines					231:252	Two to three consecutive O-linked N-acetylgalactosamines	197:252	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens)	197:266	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens) are recognized by antibodies such as MLS128.
31168022	2	64	theme	consecutive	210:220	arg1	Tn-antigens					255:265	Tn-antigens	255:265	Tn-antigens	255:265	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens) are recognized by antibodies such as MLS128.
31168022	0	65	gly	glycoprotein	107:118	arg1	glycoprotein					107:118	a 110 kDa glycoprotein	97:118	a 110 kDa glycoprotein	97:118	MLS128 antibody-induced suppression of colon cancer cell growth is mediated by a desmocollin and a 110 kDa glycoprotein.
31168022	8	66	theme	lysates	938:944	arg1	analyses					915:922	Western blotting analyses	898:922	Western blotting analyses of LS180 cell lysates	898:944	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	8	67	theme	kDa	968:970	arg1	band					972:975	a common 110 kDa band	955:975	a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein	955:1045	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	2	68	link	O-linked	222:229	arg1	N-acetylgalactosamines					231:252	Two to three consecutive O-linked N-acetylgalactosamines	197:252	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens)	197:266	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens) are recognized by antibodies such as MLS128.
31168022	2	68	link	O-linked	222:229	arg1	Tn-antigens					255:265	Tn-antigens	255:265	Tn-antigens	255:265	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens) are recognized by antibodies such as MLS128.
31168022	12	69	gly	N-glycosylation	1713:1727	arg2	sites					1729:1733	N-glycosylation sites	1713:1733	N-glycosylation sites	1713:1733	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	8	70	theme	common	957:962	arg1	band					972:975	a common 110 kDa band	955:975	a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein	955:1045	Western blotting analyses of LS180 cell lysates revealed a common 110 kDa band recognized by MLS128 and anti-desmocollin, but not by anti-desmoglein.
31168022	1	71	theme	Protein	121:127	arg1	form					156:159	a diverse form	146:159	a diverse form of post-translational modification	146:194	Protein glycosylation is a diverse form of post-translational modification.
31168022	1	71	theme	Protein	121:127	arg1	glycosylation					129:141	Protein glycosylation	121:141	Protein glycosylation	121:141	Protein glycosylation is a diverse form of post-translational modification.
31168022	11	72	theme	critical	1547:1554	arg1	role					1556:1559	a critical role	1545:1559	a critical role for this protein in cell growth and survival	1545:1604	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	12	73	theme	F	1621:1621	arg1	digestion					1623:1631	N-glycosidase F digestion	1607:1631	N-glycosidase F digestion of the 110 kDa GP and desmocollin	1607:1665	N-glycosidase F digestion of the 110 kDa GP and desmocollin suggested that although both proteins contain N-glycosylation sites, they are not identical.
31168022	11	74	theme	knock	1439:1443	arg1	down					1445:1448	knock down desmocollin expression or a desmocollin-specific antibody	1439:1506	down	1445:1448	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	9	75	theme	LS180	1081:1085	arg1	cells					1087:1091	LS180 cells	1081:1091	LS180 cells	1081:1091	Immunofluorescence microscopy of LS180 cells revealed that desmocollin is membrane-bound, while desmoglein is primarily localized in the cytosol.
31168022	11	76	theme	cells	1419:1423	arg1	Treatment					1400:1408	Treatment	1400:1408	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody	1400:1506	Treatment of LS180 cells with siRNA to knock down desmocollin expression or a desmocollin-specific antibody decreased cell viability, suggesting a critical role for this protein in cell growth and survival.
31168022	2	77	dep	three	204:208	arg1	to					201:202	to	201:202	to	201:202	Two to three consecutive O-linked N-acetylgalactosamines (Tn-antigens) are recognized by antibodies such as MLS128.
31168022	4	78	theme	kDa	477:479	arg1	GP					481:482	the 110 kDa GP	469:482	the 110 kDa GP	469:482	However, purification and identification of the 110 kDa GP was unsuccessful due to its low abundance.
31168022	6	79	theme	desmosome	724:732	arg1	components					734:743	Three desmosome components	718:743	Three desmosome components	718:743	Three desmosome components were identified.
31168022	13	80	theme	kDa	1825:1827	arg1	GP					1829:1830	the 110 kDa GP	1817:1830	the 110 kDa GP	1817:1830	These findings suggest that desmocollin colocalizes with the 110 kDa GP and that growth inhibition induced by the MLS128 antibody may be mediated through a mechanism that involves desmocollin.
31168022	9	81	theme	Immunofluorescence	1048:1065	arg1	microscopy					1067:1076	Immunofluorescence microscopy	1048:1076	Immunofluorescence microscopy of LS180 cells	1048:1091	Immunofluorescence microscopy of LS180 cells revealed that desmocollin is membrane-bound, while desmoglein is primarily localized in the cytosol.
31168022	10	82	theme	Confocal	1194:1201	arg1	microscopy					1203:1212	Confocal microscopy	1194:1212	Confocal microscopy	1194:1212	Confocal microscopy demonstrated colocalization of the desmocollin-specific antibody with the MLS128 antibody on the cell membrane, suggesting that desmocollin may contain Tn-antigens recognized by MLS128.
31110306	1	0	gly	glycosylation	91:103	arg1	mAbs					131:134	mAbs	131:134	mAbs	131:134	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	0	gly	glycosylation	91:103	arg1	antibodies					119:128	monoclonal antibodies	108:128	monoclonal antibodies (mAbs)	108:135	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	7	1	theme	in	1256:1257	arg1	effects					1277:1283	tailored in vitro and in vivo effects	1247:1283	tailored in vitro and in vivo effects	1247:1283	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	5	2	theme	orthogonal	980:989	arg1	inducers					1006:1013	orthogonal small molecule inducers	980:1013	orthogonal small molecule inducers	980:1013	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	1	3	from	glycosylation	91:103	arg1	mAbs					131:134	mAbs	131:134	mAbs	131:134	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	3	from	glycosylation	91:103	arg1	antibodies					119:128	monoclonal antibodies	108:128	monoclonal antibodies (mAbs)	108:135	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	4	theme	clinical	260:267	arg1	efficacy					269:276	clinical efficacy	260:276	clinical efficacy	260:276	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	0	5	from	control	15:21	arg1	cells					75:79	engineered mammalian cells	54:79	engineered mammalian cells	54:79	Small-molecule control of antibody N-glycosylation in engineered mammalian cells.
31110306	1	6	theme	functional	167:176	arg1	safety					249:254	safety	249:254	safety	249:254	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	6	theme	functional	167:176	arg1	efficacy					269:276	clinical efficacy	260:276	clinical efficacy	260:276	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	6	theme	functional	167:176	arg1	properties					178:187	structural and functional properties	152:187	structural and functional properties	152:187	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	6	theme	functional	167:176	arg1	stability					220:228	stability	220:228	stability	220:228	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	6	theme	functional	167:176	arg1	pharmacokinetics					231:246	pharmacokinetics	231:246	pharmacokinetics	231:246	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	7	link	N-linked	82:89	arg1	glycosylation					91:103	N-linked glycosylation	82:103	N-linked glycosylation in monoclonal antibodies (mAbs)	82:135	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	4	8	with	genes	582:586	arg1	levels					885:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	7	9	theme	tailored	1247:1254	arg1	effects					1277:1283	tailored in vitro and in vivo effects	1247:1283	tailored in vitro and in vivo effects	1247:1283	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	6	10	theme	antibody	1096:1103	arg1	binding					1105:1111	antibody binding	1096:1111	antibody binding to a cell surface receptor	1096:1138	Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor.
31110306	7	11	theme	biomedical	1318:1327	arg1	applications					1329:1340	various biotechnological and biomedical applications	1289:1340	applications	1329:1340	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	3	12	theme	expressed	524:532	arg1	IgG					534:536	a stably expressed IgG	515:536	a stably expressed IgG	515:536	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	7	13	theme	protein	1221:1227	arg1	therapeutics					1229:1240	new recombinant protein therapeutics	1205:1240	new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications	1205:1340	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	1	14	theme	N-linked	82:89	arg1	glycosylation					91:103	N-linked glycosylation	82:103	N-linked glycosylation in monoclonal antibodies (mAbs)	82:135	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	4	15	theme	constitutive	749:760	arg1	promoters					775:783	constitutive or inducible promoters	749:783	constitutive or inducible promoters	749:783	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	3	16	theme	genetic	471:477	arg1	circuits					479:486	synthetic genetic circuits	461:486	synthetic genetic circuits	461:486	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	0	17	theme	engineered	54:63	arg1	cells					75:79	engineered mammalian cells	54:79	engineered mammalian cells	54:79	Small-molecule control of antibody N-glycosylation in engineered mammalian cells.
31110306	7	18	dep	in	1269:1270	arg1	vivo					1272:1275	vivo	1272:1275	vivo	1272:1275	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	4	19	with	antibodies	799:808	arg1	levels					885:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	2	20	theme	biopharmaceutical	283:299	arg1	industry					301:308	The biopharmaceutical industry	279:308	The biopharmaceutical industry	279:308	The biopharmaceutical industry currently lacks tools to precisely control N-glycosylation levels during mAb production.
31110306	4	21	theme	glycosyltransferase	717:735	arg1	genes					737:741	synthetic glycosyltransferase genes	707:741	synthetic glycosyltransferase genes	707:741	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	6	22	theme	glycosylation	1057:1069	arg1	changes					1079:1085	glycosylation profile changes	1057:1085	glycosylation profile changes	1057:1085	Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor.
31110306	7	23	theme	new	1205:1207	arg1	therapeutics					1229:1240	new recombinant protein therapeutics	1205:1240	new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications	1205:1340	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	4	24	theme	fucosylation	836:847	arg1	levels					885:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	1	25	theme	mAb	192:194	arg1	therapeutics					196:207	mAb therapeutics	192:207	mAb therapeutics	192:207	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	0	26	theme	Small-molecule	0:13	arg1	control					15:21	Small-molecule control	0:21	Small-molecule control of antibody N-glycosylation in engineered mammalian cells	0:79	Small-molecule control of antibody N-glycosylation in engineered mammalian cells.
31110306	6	27	theme	function	1025:1032	arg1	studies					1034:1040	Effector function studies	1016:1040	Effector function studies	1016:1040	Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor.
31110306	7	28	theme	N-glycosylation	1178:1192	arg1	modification					1162:1173	Precise and rational modification	1141:1173	Precise and rational modification of N-glycosylation	1141:1192	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	1	29	theme	monoclonal	108:117	arg1	mAbs					131:134	mAbs	131:134	mAbs	131:134	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	29	theme	monoclonal	108:117	arg1	antibodies					119:128	monoclonal antibodies	108:128	monoclonal antibodies (mAbs)	108:135	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	30	theme	therapeutics	196:207	arg1	safety					249:254	safety	249:254	safety	249:254	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	30	theme	therapeutics	196:207	arg1	efficacy					269:276	clinical efficacy	260:276	clinical efficacy	260:276	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	30	theme	therapeutics	196:207	arg1	properties					178:187	structural and functional properties	152:187	structural and functional properties	152:187	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	30	theme	therapeutics	196:207	arg1	stability					220:228	stability	220:228	stability	220:228	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	30	theme	therapeutics	196:207	arg1	pharmacokinetics					231:246	pharmacokinetics	231:246	pharmacokinetics	231:246	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	0	31	theme	antibody	26:33	arg1	N-glycosylation					35:49	antibody N-glycosylation	26:49	antibody N-glycosylation	26:49	Small-molecule control of antibody N-glycosylation in engineered mammalian cells.
31110306	5	32	theme	molecule	997:1004	arg1	inducers					1006:1013	orthogonal small molecule inducers	980:1013	orthogonal small molecule inducers	980:1013	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	5	33	theme	independent	910:920	arg1	control					922:928	Simultaneous and independent control	893:928	Simultaneous and independent control of FUT8 and β4GALT1 expression	893:959	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	4	34	theme	desired	828:834	arg1	fucosylation					836:847	concurrently desired fucosylation	815:847	concurrently desired fucosylation (0-97%)	815:855	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	4	34	theme	desired	828:834	arg1	%					854:854	0-97%	850:854	0-97%	850:854	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	6	35	theme	profile	1071:1077	arg1	changes					1079:1085	glycosylation profile changes	1057:1085	glycosylation profile changes	1057:1085	Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor.
31110306	4	36	theme	galactosylation	861:875	arg1	levels					885:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	5	37	theme	small	991:995	arg1	inducers					1006:1013	orthogonal small molecule inducers	980:1013	orthogonal small molecule inducers	980:1013	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	4	38	theme	integrated	676:685	arg1	circuits					687:694	genomically integrated circuits	664:694	genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters	664:783	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	3	39	theme	ovary	444:448	arg1	cells					450:454	Chinese hamster ovary cells	428:454	Chinese hamster ovary cells with synthetic genetic circuits	428:486	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	4	40	theme	generated	789:797	arg1	antibodies					799:808	generated antibodies	789:808	generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	789:890	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	7	41	dep	in	1256:1257	arg1	vitro					1259:1263	vitro	1259:1263	vitro	1259:1263	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	3	42	theme	synthetic	461:469	arg1	circuits					479:486	synthetic genetic circuits	461:486	synthetic genetic circuits	461:486	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	4	43	theme	synthetic	707:715	arg1	genes					737:741	synthetic glycosyltransferase genes	707:741	synthetic glycosyltransferase genes	707:741	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	0	44	theme	N-glycosylation	35:49	arg1	control					15:21	Small-molecule control	0:21	Small-molecule control of antibody N-glycosylation in engineered mammalian cells	0:79	Small-molecule control of antibody N-glycosylation in engineered mammalian cells.
31110306	4	45	theme	key	558:560	arg1	β-1,4-galactosyltransferase					625:651	β-1,4-galactosyltransferase	625:651	β-1,4-galactosyltransferase (β4GALT1)	625:661	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	4	45	theme	key	558:560	arg1	α-1,6-fucosyltransferase					589:612	α-1,6-fucosyltransferase	589:612	α-1,6-fucosyltransferase (FUT8)	589:619	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	4	45	theme	key	558:560	arg1	genes					582:586	two key glycosyltransferase genes	554:586	two key glycosyltransferase genes	554:586	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	5	46	theme	expression	950:959	arg1	control					922:928	Simultaneous and independent control	893:928	Simultaneous and independent control of FUT8 and β4GALT1 expression	893:959	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	3	47	gly	N-glycosylation	496:510	arg1	IgG					534:536	a stably expressed IgG	515:536	a stably expressed IgG	515:536	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	5	48	theme	FUT8	933:936	arg1	control					922:928	Simultaneous and independent control	893:928	Simultaneous and independent control of FUT8 and β4GALT1 expression	893:959	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	0	49	theme	mammalian	65:73	arg1	cells					75:79	engineered mammalian cells	54:79	engineered mammalian cells	54:79	Small-molecule control of antibody N-glycosylation in engineered mammalian cells.
31110306	7	50	theme	rational	1153:1160	arg1	modification					1162:1173	Precise and rational modification	1141:1173	Precise and rational modification of N-glycosylation	1141:1192	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	2	51	theme	mAb	383:385	arg1	production					387:396	mAb production	383:396	mAb production	383:396	The biopharmaceutical industry currently lacks tools to precisely control N-glycosylation levels during mAb production.
31110306	3	52	theme	hamster	436:442	arg1	cells					450:454	Chinese hamster ovary cells	428:454	Chinese hamster ovary cells with synthetic genetic circuits	428:486	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	7	53	with	therapeutics	1229:1240	arg1	effects					1277:1283	tailored in vitro and in vivo effects	1247:1283	tailored in vitro and in vivo effects	1247:1283	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	5	54	theme	Simultaneous	893:904	arg1	control					922:928	Simultaneous and independent control	893:928	Simultaneous and independent control of FUT8 and β4GALT1 expression	893:959	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	3	55	theme	IgG	534:536	arg1	N-glycosylation					496:510	N-glycosylation	496:510	N-glycosylation of a stably expressed IgG	496:536	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	4	56	theme	glycosyltransferase	562:580	arg1	β-1,4-galactosyltransferase					625:651	β-1,4-galactosyltransferase	625:651	β-1,4-galactosyltransferase (β4GALT1)	625:661	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	4	56	theme	glycosyltransferase	562:580	arg1	α-1,6-fucosyltransferase					589:612	α-1,6-fucosyltransferase	589:612	α-1,6-fucosyltransferase (FUT8)	589:619	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	4	56	theme	glycosyltransferase	562:580	arg1	genes					582:586	two key glycosyltransferase genes	554:586	two key glycosyltransferase genes	554:586	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	7	57	theme	Precise	1141:1147	arg1	modification					1162:1173	Precise and rational modification	1141:1173	Precise and rational modification of N-glycosylation	1141:1192	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	7	58	theme	in	1269:1270	arg1	effects					1277:1283	tailored in vitro and in vivo effects	1247:1283	tailored in vitro and in vivo effects	1247:1283	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	3	59	with	cells	450:454	arg1	circuits					479:486	synthetic genetic circuits	461:486	synthetic genetic circuits	461:486	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	4	60	with	circuits	687:694	arg1	levels					885:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels	815:890	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	2	61	theme	N-glycosylation	353:367	arg1	levels					369:374	N-glycosylation levels	353:374	N-glycosylation levels	353:374	The biopharmaceutical industry currently lacks tools to precisely control N-glycosylation levels during mAb production.
31110306	7	62	theme	recombinant	1209:1219	arg1	therapeutics					1229:1240	new recombinant protein therapeutics	1205:1240	new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications	1205:1340	Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.
31110306	4	63	theme	inducible	765:773	arg1	promoters					775:783	constitutive or inducible promoters	749:783	constitutive or inducible promoters	749:783	We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels.
31110306	5	64	theme	β4GALT1	942:948	arg1	expression					950:959	β4GALT1 expression	942:959	β4GALT1 expression	942:959	Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers.
31110306	6	65	theme	surface	1123:1129	arg1	receptor					1131:1138	a cell surface receptor	1116:1138	a cell surface receptor	1116:1138	Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor.
31110306	3	66	theme	Chinese	428:434	arg1	cells					450:454	Chinese hamster ovary cells	428:454	Chinese hamster ovary cells with synthetic genetic circuits	428:486	In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG.
31110306	6	67	theme	Effector	1016:1023	arg1	studies					1034:1040	Effector function studies	1016:1040	Effector function studies	1016:1040	Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor.
31110306	1	68	theme	structural	152:161	arg1	safety					249:254	safety	249:254	safety	249:254	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	68	theme	structural	152:161	arg1	efficacy					269:276	clinical efficacy	260:276	clinical efficacy	260:276	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	68	theme	structural	152:161	arg1	properties					178:187	structural and functional properties	152:187	structural and functional properties	152:187	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	68	theme	structural	152:161	arg1	stability					220:228	stability	220:228	stability	220:228	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	1	68	theme	structural	152:161	arg1	pharmacokinetics					231:246	pharmacokinetics	231:246	pharmacokinetics	231:246	N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy.
31110306	6	69	theme	cell	1118:1121	arg1	receptor					1131:1138	a cell surface receptor	1116:1138	a cell surface receptor	1116:1138	Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor.
31086219	0	0	from	recognition	15:25	arg1	Trypanosoma					30:40	Trypanosoma	30:40	Trypanosoma	30:40	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.
31086219	0	0	from	recognition	15:25	arg1	adhesin					53:59	GP82 adhesin	48:59	GP82 adhesin	48:59	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.
31086219	5	1	theme	electrophoretic	839:853	arg1	mobility					855:862	indistinguishable electrophoretic mobility	821:862	indistinguishable electrophoretic mobility	821:862	Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP.
31086219	2	2	theme	up-stream	352:360	arg1	codons					337:342	several in-frame initiation codons	309:342	several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	309:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	9	3	theme	experimental	1461:1472	arg1	characterization					1474:1489	the first experimental characterization	1451:1489	the first experimental characterization of the full-length GP82 and its signal peptide	1451:1536	This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
31086219	1	4	theme	Chagas	153:158	arg1	disease					160:166	Chagas disease	153:166	Chagas disease	153:166	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	8	5	from	N-terminus	1418:1427	arg1	localization					1394:1405	the signal localization	1383:1405	the signal localization at protein N-terminus	1383:1427	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	6	6	theme	precursor	1029:1037	arg1	identification					1006:1019	irrefutable identification	994:1019	irrefutable identification of GP82 precursor	994:1037	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	0	7	theme	protein	91:97	arg1	N-terminus					99:108	protein N-terminus	91:108	protein N-terminus	91:108	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.
31086219	6	8	theme	SP	918:919	arg1	Deletion					906:913	Deletion	906:913	Deletion of SP	906:919	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	3	9	theme	farthest	519:526	arg1	methionine					538:547	the farthest up-stream methionine	515:547	the farthest up-stream methionine	515:547	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	6	10	theme	irrefutable	994:1004	arg1	identification					1006:1019	irrefutable identification	994:1019	irrefutable identification of GP82 precursor	994:1037	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	3	11	theme	up-stream	528:536	arg1	methionine					538:547	the farthest up-stream methionine	515:547	the farthest up-stream methionine	515:547	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	9	12	theme	signal	1523:1528	arg1	peptide					1530:1536	its signal peptide	1519:1536	its signal peptide	1519:1536	This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
31086219	5	13	theme	similar	876:882	arg1	processing					884:893	similar processing	876:893	similar processing of the SP	876:903	Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP.
31086219	4	14	theme	HeLa	701:704	arg1	cells					706:710	HeLa cells	701:710	HeLa cells	701:710	Proteins were fully functional, inducing parasite adhesion to HeLa cells and lysosome mobilization, events required for parasite invasion.
31086219	7	15	theme	signal	1129:1134	arg1	peptidase					1136:1144	the signal peptidase	1125:1144	the signal peptidase	1125:1144	SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association.
31086219	9	16	theme	peptide	1530:1536	arg1	characterization					1474:1489	the first experimental characterization	1451:1489	the first experimental characterization of the full-length GP82 and its signal peptide	1451:1536	This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
31086219	1	17	theme	disease	160:166	arg1	agent					144:148	the causative agent	130:148	the causative agent of Chagas disease	130:166	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	1	17	theme	disease	160:166	arg1	cruzi					123:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	5	18	theme	native	793:798	arg1	proteins					805:812	Transgenic and native GP82 proteins	778:812	Transgenic and native GP82 proteins	778:812	Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP.
31086219	8	19	theme	strict	1362:1367	arg1	dependence					1369:1378	strict dependence	1362:1378	strict dependence on the signal localization at protein N-terminus	1362:1427	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	3	20	dep	T.	435:436	arg1	cruzi					438:442	cruzi	438:442	cruzi	438:442	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	4	21	theme	parasite	759:766	arg1	invasion					768:775	parasite invasion	759:775	parasite invasion	759:775	Proteins were fully functional, inducing parasite adhesion to HeLa cells and lysosome mobilization, events required for parasite invasion.
31086219	8	22	dep	peptidase	1346:1354	arg1	shows					1356:1360	shows	1356:1360	shows strict dependence on the signal localization at protein N-terminus	1356:1427	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	0	23	theme	peptide	7:13	arg1	recognition					15:25	Signal peptide recognition	0:25	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin	0:59	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.
31086219	8	24	from	dependence	1369:1378	arg1	localization					1394:1405	the signal localization	1383:1405	the signal localization at protein N-terminus	1383:1427	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	3	25	theme	protein	559:565	arg1	expression					567:576	protein expression	559:576	protein expression	559:576	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	8	26	theme	transmembrane	1291:1303	arg1	domain					1305:1310	transmembrane domain	1291:1310	transmembrane domain	1291:1310	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	0	27	theme	Signal	0:5	arg1	recognition					15:25	Signal peptide recognition	0:25	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin	0:59	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.
31086219	2	28	from	that	367:370	arg1	up-stream					352:360	up-stream	352:360	up-stream	352:360	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	29	theme	transcripts	286:296	arg1	transcripts					286:296	transcripts	286:296	transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	286:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	29	theme	transcripts	286:296	arg1	repertoire					272:281	a repertoire	270:281	a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	270:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	7	30	theme	ER-membrane	1194:1204	arg1	association					1206:1216	ER-membrane association	1194:1216	ER-membrane association	1194:1216	SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association.
31086219	6	31	link	N-linked	959:966	arg1	oligosaccharides					968:983	N-linked oligosaccharides	959:983	N-linked oligosaccharides allowing irrefutable identification of GP82 precursor	959:1037	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	7	32	theme	signal	1100:1105	arg1	unrecognizable					1107:1120	the signal unrecognizable	1096:1120	the signal unrecognizable	1096:1120	SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association.
31086219	9	33	theme	full-length	1498:1508	arg1	GP82					1510:1513	the full-length GP82	1494:1513	the full-length GP82	1494:1513	This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
31086219	3	34	theme	parasite	585:592	arg1	surface					599:605	the parasite cell surface	581:605	the parasite cell surface	581:605	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	1	35	theme	dense	175:179	arg1	coat					181:184	a dense coat	173:184	a dense coat of GPI-anchored virulence factors	173:218	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	4	36	theme	lysosome	716:723	arg1	mobilization					725:736	lysosome mobilization	716:736	lysosome mobilization	716:736	Proteins were fully functional, inducing parasite adhesion to HeLa cells and lysosome mobilization, events required for parasite invasion.
31086219	4	37	theme	parasite	680:687	arg1	adhesion					689:696	parasite adhesion	680:696	parasite adhesion to HeLa cells	680:710	Proteins were fully functional, inducing parasite adhesion to HeLa cells and lysosome mobilization, events required for parasite invasion.
31086219	4	37	theme	parasite	680:687	arg1	events					739:744	events	739:744	events required for parasite invasion	739:775	Proteins were fully functional, inducing parasite adhesion to HeLa cells and lysosome mobilization, events required for parasite invasion.
31086219	3	38	theme	T.	435:436	arg1	epimastigotes					444:456	T. cruzi epimastigotes	435:456	T. cruzi epimastigotes	435:456	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	5	39	theme	SP	902:903	arg1	processing					884:893	similar processing	876:893	similar processing of the SP	876:903	Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP.
31086219	8	40	theme	GP82	1262:1265	arg1	SP					1267:1268	GP82 SP	1262:1268	GP82 SP	1262:1268	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	6	41	theme	oligosaccharides	968:983	arg1	devoid					949:954	devoid	949:954	devoid	949:954	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	1	42	contain	has	169:171	arg1	agent					144:148	the causative agent	130:148	the causative agent of Chagas disease	130:166	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	1	42	contain	has	169:171	arg2	coat					181:184	a dense coat	173:184	a dense coat of GPI-anchored virulence factors	173:218	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	1	42	contain	has	169:171	arg1	cruzi					123:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	2	43	theme	T.	221:222	arg1	GP82					251:254	T. cruzi GPI-anchored adhesin GP82	221:254	T. cruzi GPI-anchored adhesin GP82	221:254	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	44	dep	T.	221:222	arg1	cruzi					224:228	cruzi	224:228	cruzi	224:228	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	45	theme	predicted	388:396	arg1	peptide					405:411	the predicted signal peptide	384:411	the predicted signal peptide (SP)	384:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	45	theme	predicted	388:396	arg1	SP					414:415	SP	414:415	SP	414:415	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	6	46	theme	N-linked	959:966	arg1	oligosaccharides					968:983	N-linked oligosaccharides	959:983	N-linked oligosaccharides allowing irrefutable identification of GP82 precursor	959:1037	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	5	47	theme	Transgenic	778:787	arg1	proteins					805:812	Transgenic and native GP82 proteins	778:812	Transgenic and native GP82 proteins	778:812	Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP.
31086219	7	48	theme	nascent	1174:1180	arg1	protein					1182:1188	the nascent protein	1170:1188	the nascent protein for ER-membrane association	1170:1216	SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association.
31086219	3	49	theme	cell	594:597	arg1	surface					599:605	the parasite cell surface	581:605	the parasite cell surface	581:605	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	8	50	theme	signal	1339:1344	arg1	peptidase					1346:1354	the signal peptidase	1335:1354	the signal peptidase shows strict dependence on the signal localization at protein N-terminus	1335:1427	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	2	51	theme	signal	398:403	arg1	peptide					405:411	the predicted signal peptide	384:411	the predicted signal peptide (SP)	384:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	51	theme	signal	398:403	arg1	SP					414:415	SP	414:415	SP	414:415	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	9	52	theme	GP82	1510:1513	arg1	characterization					1474:1489	the first experimental characterization	1451:1489	the first experimental characterization of the full-length GP82 and its signal peptide	1451:1536	This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
31086219	8	53	theme	signal	1387:1392	arg1	localization					1394:1405	the signal localization	1383:1405	the signal localization at protein N-terminus	1383:1427	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	3	54	theme	native	626:631	arg1	GP82					633:636	the native GP82	622:636	the native GP82	622:636	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	7	55	theme	internal	1063:1070	arg1	region					1072:1077	an internal region	1060:1077	an internal region of GP82	1060:1085	SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association.
31086219	1	56	theme	Trypanosoma	111:121	arg1	agent					144:148	the causative agent	130:148	the causative agent of Chagas disease	130:166	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	1	56	theme	Trypanosoma	111:121	arg1	cruzi					123:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	0	57	theme	GP82	48:51	arg1	adhesin					53:59	GP82 adhesin	48:59	GP82 adhesin	48:59	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.
31086219	6	58	theme	devoid	949:954	arg1	protein					941:947	a ~72 kDa protein	931:947	a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor	931:1037	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	7	59	theme	GP82	1082:1085	arg1	region					1072:1077	an internal region	1060:1077	an internal region of GP82	1060:1085	SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association.
31086219	7	60	theme	SP	1040:1041	arg1	transposition					1043:1055	SP transposition	1040:1055	SP transposition to an internal region of GP82	1040:1085	SP transposition to an internal region of GP82 rendered the signal unrecognizable by the signal peptidase and incapable to direct the nascent protein for ER-membrane association.
31086219	2	61	theme	initiation	326:335	arg1	codons					337:342	several in-frame initiation codons	309:342	several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	309:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	62	contain	containing	298:307	arg2	codons					337:342	several in-frame initiation codons	309:342	several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	309:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	62	contain	containing	298:307	arg1	transcripts					286:296	transcripts	286:296	transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	286:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	3	63	with	Transfection	419:430	arg1	constructs					463:472	constructs	463:472	constructs encoding GP82 starting at the SP or from the farthest up-stream methionine	463:547	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	0	64	from	N-terminus	99:108	arg1	localization					75:86	its localization	71:86	its localization at protein N-terminus	71:108	Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.
31086219	3	65	theme	comparable	608:617	arg1	expression					567:576	protein expression	559:576	protein expression	559:576	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	2	66	theme	in-frame	317:324	arg1	codons					337:342	several in-frame initiation codons	309:342	several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	309:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	1	67	theme	virulence	202:210	arg1	factors					212:218	GPI-anchored virulence factors	189:218	GPI-anchored virulence factors	189:218	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	2	68	theme	adhesin	243:249	arg1	GP82					251:254	T. cruzi GPI-anchored adhesin GP82	221:254	T. cruzi GPI-anchored adhesin GP82	221:254	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	2	69	theme	several	309:315	arg1	codons					337:342	several in-frame initiation codons	309:342	several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP)	309:416	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	8	70	theme	protein	1410:1416	arg1	N-terminus					1418:1427	protein N-terminus	1410:1427	protein N-terminus	1410:1427	Altogether our data strongly suggests that GP82 SP fails to function as transmembrane domain and its recognition by the signal peptidase shows strict dependence on the signal localization at protein N-terminus.
31086219	1	71	theme	factors	212:218	arg1	coat					181:184	a dense coat	173:184	a dense coat of GPI-anchored virulence factors	173:218	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	1	72	theme	GPI-anchored	189:200	arg1	factors					212:218	GPI-anchored virulence factors	189:218	GPI-anchored virulence factors	189:218	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	2	73	theme	GPI-anchored	230:241	arg1	GP82					251:254	T. cruzi GPI-anchored adhesin GP82	221:254	T. cruzi GPI-anchored adhesin GP82	221:254	T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).
31086219	3	74	theme	epimastigotes	444:456	arg1	Transfection					419:430	Transfection	419:430	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine	419:547	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	1	75	theme	causative	134:142	arg1	agent					144:148	the causative agent	130:148	the causative agent of Chagas disease	130:166	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	1	75	theme	causative	134:142	arg1	cruzi					123:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi	111:127	Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors.
31086219	3	76	from	expression	567:576	arg1	surface					599:605	the parasite cell surface	581:605	the parasite cell surface	581:605	Transfection of T. cruzi epimastigotes with constructs encoding GP82 starting at the SP or from the farthest up-stream methionine confirmed protein expression on the parasite cell surface, comparable to the native GP82.
31086219	6	77	theme	~72 kDa	933:939	arg1	protein					941:947	a ~72 kDa protein	931:947	a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor	931:1037	Deletion of SP generated a ~72 kDa protein devoid of N-linked oligosaccharides allowing irrefutable identification of GP82 precursor.
31086219	5	78	theme	indistinguishable	821:837	arg1	mobility					855:862	indistinguishable electrophoretic mobility	821:862	indistinguishable electrophoretic mobility	821:862	Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP.
31086219	5	79	theme	GP82	800:803	arg1	proteins					805:812	Transgenic and native GP82 proteins	778:812	Transgenic and native GP82 proteins	778:812	Transgenic and native GP82 proteins showed indistinguishable electrophoretic mobility, suggesting similar processing of the SP.
31086219	9	80	theme	first	1455:1459	arg1	characterization					1474:1489	the first experimental characterization	1451:1489	the first experimental characterization of the full-length GP82 and its signal peptide	1451:1536	This report presents the first experimental characterization of the full-length GP82 and its signal peptide.
30932369	3	0	theme	cognate	650:656	arg1	partner					663:669	its cognate DSPP partner	646:669	its cognate DSPP partner	646:669	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	2	1	theme	oral	562:565	arg1	carcinogenesis					567:580	oral carcinogenesis	562:580	oral carcinogenesis	562:580	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	9	2	theme	disease	1629:1635	arg1	activity					1637:1644	disease activity	1629:1644	disease activity	1629:1644	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	7	3	theme	DSPP	1346:1349	arg1	expression					1351:1360	DSPP expression	1346:1360	DSPP expression	1346:1360	DSPP expression increased significantly with tumor stage in all cancers examined.
30932369	3	4	from	expression	622:631	arg1	breast					678:683	breast	678:683	breast	678:683	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	3	4	from	expression	622:631	arg1	neoplasms					725:733	cervical neoplasms	716:733	cervical neoplasms	716:733	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	3	4	from	expression	622:631	arg1	thyroid					703:709	thyroid	703:709	thyroid	703:709	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	3	4	from	expression	622:631	arg1	prostate					693:700	prostate	693:700	prostate	693:700	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	3	4	from	expression	622:631	arg1	colon					686:690	colon	686:690	colon	686:690	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	7	5	theme	tumor	1391:1395	arg1	stage					1397:1401	tumor stage	1391:1401	tumor stage	1391:1401	DSPP expression increased significantly with tumor stage in all cancers examined.
30932369	9	6	theme	prognostic	1693:1702	arg1	implications					1704:1715	diagnostic and prognostic implications	1678:1715	diagnostic and prognostic implications	1678:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	9	7	theme	potential	1609:1617	arg1	marker					1619:1624	a potential marker	1607:1624	a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications	1607:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	9	7	theme	potential	1609:1617	arg1	pairing					1596:1602	MMP20-DSPP pairing	1585:1602	MMP20-DSPP pairing	1585:1602	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	4	8	theme	assay	881:885	arg1	experiments					905:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	2	9	theme	dentin	304:309	arg1	sialophosphoprotein					311:329	dentin sialophosphoprotein	304:329	dentin sialophosphoprotein (DSPP)	304:336	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	9	theme	dentin	304:309	arg1	member					341:346	a member	339:346	a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	339:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	9	theme	dentin	304:309	arg1	DSPP					332:335	DSPP	332:335	DSPP	332:335	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	1	10	theme	limited	212:218	arg1	expression					201:210	expression	201:210	expression limited to dental hard tissues	201:241	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	4	11	theme	normal	1035:1040	arg1	counterparts					1042:1053	their normal counterparts	1029:1053	their normal counterparts	1029:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	3	12	theme	cervical	716:723	arg1	neoplasms					725:733	cervical neoplasms	716:733	cervical neoplasms	716:733	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	8	13	from	cancers	1554:1560	arg1	present					1537:1543	present	1537:1543	present	1537:1543	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	1	14	theme	dental	223:228	arg1	tissues					235:241	dental hard tissues	223:241	dental hard tissues	223:241	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	4	15	theme	immunofluorescence	842:859	arg1	experiments					905:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	0	16	from	metalloproteinase-20	60:79	arg1	cancers					90:96	human cancers	84:96	human cancers	84:96	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	4	17	from	neoplasms	1014:1022	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	18	theme	proximity	862:870	arg1	assay					881:885	proximity ligation assay	862:885	proximity ligation assay	862:885	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	2	19	with	expression	272:281	arg1	sialophosphoprotein					311:329	dentin sialophosphoprotein	304:329	dentin sialophosphoprotein (DSPP)	304:336	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	19	with	expression	272:281	arg1	member					341:346	a member	339:346	a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	339:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	19	with	expression	272:281	arg1	DSPP					332:335	DSPP	332:335	DSPP	332:335	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	20	theme	oral	480:483	arg1	lesions					498:504	dysplastic oral premalignant lesions	469:504	dysplastic oral premalignant lesions (OPLs)	469:511	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	20	theme	oral	480:483	arg1	OPLs					507:510	OPLs	507:510	OPLs	507:510	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	21	with	interaction	287:297	arg1	sialophosphoprotein					311:329	dentin sialophosphoprotein	304:329	dentin sialophosphoprotein (DSPP)	304:336	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	21	with	interaction	287:297	arg1	member					341:346	a member	339:346	a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	339:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	21	with	interaction	287:297	arg1	DSPP					332:335	DSPP	332:335	DSPP	332:335	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	0	22	theme	human	84:88	arg1	cancers					90:96	human cancers	84:96	human cancers	84:96	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	4	23	theme	blot	900:903	arg1	experiments					905:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	0	24	from	Survey	0:5	arg1	cancers					90:96	human cancers	84:96	human cancers	84:96	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	8	25	theme	potential	1464:1472	arg1	interaction					1485:1495	potential MMP20-DSPP interaction	1464:1495	potential MMP20-DSPP interaction	1464:1495	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	2	26	theme	Glycoproteins	394:406	arg1	sialophosphoprotein					311:329	dentin sialophosphoprotein	304:329	dentin sialophosphoprotein (DSPP)	304:336	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	26	theme	Glycoproteins	394:406	arg1	member					341:346	a member	339:346	a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	339:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	6	27	theme	MMP20	1272:1276	arg1	levels					1278:1283	MMP20 levels	1272:1283	MMP20 levels	1272:1283	Furthermore, MMP20 levels increased with advanced stages of colon and thyroid cancers.
30932369	2	28	theme	squamous	434:441	arg1	carcinoma					448:456	human oral squamous cell carcinoma	423:456	human oral squamous cell carcinoma (OSCC)	423:463	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	28	theme	squamous	434:441	arg1	OSCC					459:462	OSCC	459:462	OSCC	459:462	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	29	theme	Ligand	378:383	arg1	SIBLINGs					409:416	SIBLINGs	409:416	SIBLINGs	409:416	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	29	theme	Ligand	378:383	arg1	Glycoproteins					394:406	the Small Integrin Binding Ligand N-linked Glycoproteins	351:406	the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	351:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	4	30	from	colon	979:983	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	1	31	theme	BACKGROUND	99:108	arg1	MMP20					140:144	MMP20	140:144	MMP20	140:144	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	1	31	theme	BACKGROUND	99:108	arg1	metalloproteinases-20					117:137	BACKGROUND Matrix metalloproteinases-20	99:137	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression	99:156	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	2	32	theme	human	423:427	arg1	carcinoma					448:456	human oral squamous cell carcinoma	423:456	human oral squamous cell carcinoma (OSCC)	423:463	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	32	theme	human	423:427	arg1	OSCC					459:462	OSCC	459:462	OSCC	459:462	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	5	33	theme	benign	1227:1232	arg1	counterparts					1245:1256	their benign and normal counterparts	1221:1256	their benign and normal counterparts	1221:1256	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	0	34	theme	dentin	10:15	arg1	sialophosphoprotein					17:35	dentin sialophosphoprotein	10:35	dentin sialophosphoprotein	10:35	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	4	35	from	breast	971:976	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	1	36	theme	metalloproteinases-20	117:137	arg1	expression					147:156	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression	99:156	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression	99:156	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	8	37	theme	oral	1520:1523	arg1	cancers					1525:1531	oral cancers	1520:1531	oral cancers	1520:1531	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	5	38	theme	normal	1238:1243	arg1	counterparts					1245:1256	their benign and normal counterparts	1221:1256	their benign and normal counterparts	1221:1256	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	6	39	theme	cancers	1337:1343	arg1	stages					1309:1314	advanced stages	1300:1314	advanced stages of colon and thyroid cancers	1300:1343	Furthermore, MMP20 levels increased with advanced stages of colon and thyroid cancers.
30932369	5	40	theme	expression	1083:1092	arg1	levels					1094:1099	high expression levels	1078:1099	high expression levels of MMP20 and DSPP	1078:1117	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	4	41	theme	immunohistochemistry	820:839	arg1	experiments					905:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments	820:915	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	2	42	link	N-linked	385:392	arg1	SIBLINGs					409:416	SIBLINGs	409:416	SIBLINGs	409:416	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	42	link	N-linked	385:392	arg1	Glycoproteins					394:406	the Small Integrin Binding Ligand N-linked Glycoproteins	351:406	the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	351:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	0	43	theme	cognate	45:51	arg1	metalloproteinase-20					60:79	its cognate matrix metalloproteinase-20	41:79	its cognate matrix metalloproteinase-20 in human cancers	41:96	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	4	44	theme	cervical	1005:1012	arg1	neoplasms					1014:1022	cervical neoplasms	1005:1022	cervical neoplasms	1005:1022	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	1	45	theme	hard	230:233	arg1	tissues					235:241	dental hard tissues	223:241	dental hard tissues	223:241	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	9	46	theme	MMP20-DSPP	1585:1594	arg1	marker					1619:1624	a potential marker	1607:1624	a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications	1607:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	9	46	theme	MMP20-DSPP	1585:1594	arg1	pairing					1596:1602	MMP20-DSPP pairing	1585:1602	MMP20-DSPP pairing	1585:1602	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	3	47	theme	MMP20	636:640	arg1	expression					622:631	the expression	618:631	the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms	618:733	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	4	48	theme	available	755:763	arg1	microarrays					772:782	commercially available tissue microarrays	742:782	commercially available tissue microarrays (TMAs)	742:789	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	48	theme	available	755:763	arg1	TMAs					785:788	TMAs	785:788	TMAs	785:788	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	2	49	theme	Integrin	361:368	arg1	SIBLINGs					409:416	SIBLINGs	409:416	SIBLINGs	409:416	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	49	theme	Integrin	361:368	arg1	Glycoproteins					394:406	the Small Integrin Binding Ligand N-linked Glycoproteins	351:406	the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	351:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	6	50	theme	thyroid	1329:1335	arg1	cancers					1337:1343	thyroid cancers	1329:1343	thyroid cancers	1329:1343	Furthermore, MMP20 levels increased with advanced stages of colon and thyroid cancers.
30932369	4	51	from	DSPP	959:962	arg1	prostate					986:993	prostate	986:993	prostate	986:993	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	51	from	DSPP	959:962	arg1	thyroid					996:1002	thyroid	996:1002	thyroid	996:1002	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	51	from	DSPP	959:962	arg1	breast					971:976	breast	971:976	breast	971:976	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	51	from	DSPP	959:962	arg1	counterparts					1042:1053	their normal counterparts	1029:1053	their normal counterparts	1029:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	51	from	DSPP	959:962	arg1	colon					979:983	colon	979:983	colon	979:983	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	51	from	DSPP	959:962	arg1	neoplasms					1014:1022	cervical neoplasms	1005:1022	cervical neoplasms	1005:1022	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	52	from	counterparts	1042:1053	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	8	53	from	present	1537:1543	arg1	cancers					1554:1560	other cancers	1548:1560	other cancers	1548:1560	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	2	54	from	role	527:530	arg1	carcinogenesis					567:580	oral carcinogenesis	562:580	oral carcinogenesis	562:580	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	3	55	theme	DSPP	658:661	arg1	partner					663:669	its cognate DSPP partner	646:669	its cognate DSPP partner	646:669	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	5	56	theme	malignant	1140:1148	arg1	breast					1150:1155	the malignant breast	1136:1155	the malignant breast	1136:1155	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	2	57	theme	cell	443:446	arg1	carcinoma					448:456	human oral squamous cell carcinoma	423:456	human oral squamous cell carcinoma (OSCC)	423:463	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	57	theme	cell	443:446	arg1	OSCC					459:462	OSCC	459:462	OSCC	459:462	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	9	58	theme	activity	1637:1644	arg1	marker					1619:1624	a potential marker	1607:1624	a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications	1607:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	9	58	theme	activity	1637:1644	arg1	pairing					1596:1602	MMP20-DSPP pairing	1585:1602	MMP20-DSPP pairing	1585:1602	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	6	59	theme	advanced	1300:1307	arg1	stages					1309:1314	advanced stages	1300:1314	advanced stages of colon and thyroid cancers	1300:1343	Furthermore, MMP20 levels increased with advanced stages of colon and thyroid cancers.
30932369	4	60	dep	breast	971:976	arg1	the					967:969	the	967:969	the	967:969	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	61	theme	cell	795:798	arg1	lines					800:804	cell lines	795:804	cell lines	795:804	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	3	62	dep	METHODS	583:589	arg1	aimed					602:606	aimed	602:606	aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms	602:733	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	4	63	theme	ligation	872:879	arg1	assay					881:885	proximity ligation assay	862:885	proximity ligation assay	862:885	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	9	64	from	marker	1619:1624	arg1	cancers					1665:1671	some epithelial cancers	1649:1671	some epithelial cancers with diagnostic and prognostic implications	1649:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	9	65	theme	diagnostic	1678:1687	arg1	implications					1704:1715	diagnostic and prognostic implications	1678:1715	diagnostic and prognostic implications	1678:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	4	66	from	MMP20	949:953	arg1	prostate					986:993	prostate	986:993	prostate	986:993	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	66	from	MMP20	949:953	arg1	thyroid					996:1002	thyroid	996:1002	thyroid	996:1002	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	66	from	MMP20	949:953	arg1	breast					971:976	breast	971:976	breast	971:976	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	66	from	MMP20	949:953	arg1	counterparts					1042:1053	their normal counterparts	1029:1053	their normal counterparts	1029:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	66	from	MMP20	949:953	arg1	colon					979:983	colon	979:983	colon	979:983	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	66	from	MMP20	949:953	arg1	neoplasms					1014:1022	cervical neoplasms	1005:1022	cervical neoplasms	1005:1022	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	9	67	theme	epithelial	1654:1663	arg1	cancers					1665:1671	some epithelial cancers	1649:1671	some epithelial cancers with diagnostic and prognostic implications	1649:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	2	68	theme	MMP20-DSPP	536:545	arg1	interaction					547:557	MMP20-DSPP interaction	536:557	MMP20-DSPP interaction	536:557	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	5	69	theme	cervical	1188:1195	arg1	neoplasms					1197:1205	cervical neoplasms	1188:1205	cervical neoplasms	1188:1205	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	2	70	theme	MMP20	266:270	arg1	expression					272:281	MMP20 expression	266:281	MMP20 expression	266:281	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	71	from	expression	272:281	arg1	carcinoma					448:456	human oral squamous cell carcinoma	423:456	human oral squamous cell carcinoma (OSCC)	423:463	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	71	from	expression	272:281	arg1	OSCC					459:462	OSCC	459:462	OSCC	459:462	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	71	from	expression	272:281	arg1	OPLs					507:510	OPLs	507:510	OPLs	507:510	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	71	from	expression	272:281	arg1	lesions					498:504	dysplastic oral premalignant lesions	469:504	dysplastic oral premalignant lesions (OPLs)	469:511	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	6	72	theme	colon	1319:1323	arg1	stages					1309:1314	advanced stages	1300:1314	advanced stages of colon and thyroid cancers	1300:1343	Furthermore, MMP20 levels increased with advanced stages of colon and thyroid cancers.
30932369	8	73	attach	present	1537:1543	arg2	CONCLUSIONS					1428:1438	CONCLUSIONS	1428:1438	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers	1428:1531	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	8	73	attach	present	1537:1543	arg1	cancers					1554:1560	other cancers	1548:1560	other cancers	1548:1560	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	4	74	from	thyroid	996:1002	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	2	75	from	interaction	287:297	arg1	carcinoma					448:456	human oral squamous cell carcinoma	423:456	human oral squamous cell carcinoma (OSCC)	423:463	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	75	from	interaction	287:297	arg1	OSCC					459:462	OSCC	459:462	OSCC	459:462	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	75	from	interaction	287:297	arg1	OPLs					507:510	OPLs	507:510	OPLs	507:510	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	75	from	interaction	287:297	arg1	lesions					498:504	dysplastic oral premalignant lesions	469:504	dysplastic oral premalignant lesions (OPLs)	469:511	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	76	theme	dysplastic	469:478	arg1	lesions					498:504	dysplastic oral premalignant lesions	469:504	dysplastic oral premalignant lesions (OPLs)	469:511	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	76	theme	dysplastic	469:478	arg1	OPLs					507:510	OPLs	507:510	OPLs	507:510	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	4	77	from	prostate	986:993	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	5	78	theme	high	1078:1081	arg1	levels					1094:1099	high expression levels	1078:1099	high expression levels of MMP20 and DSPP	1078:1117	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	4	79	theme	western	892:898	arg1	blot					900:903	western blot	892:903	western blot	892:903	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	8	80	theme	MMP20-DSPP	1474:1483	arg1	interaction					1485:1495	potential MMP20-DSPP interaction	1464:1495	potential MMP20-DSPP interaction	1464:1495	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	5	81	located	observed	1124:1131	arg1	breast					1150:1155	the malignant breast	1136:1155	the malignant breast	1136:1155	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	5	81	located	observed	1124:1131	arg1	thyroid					1175:1181	thyroid	1175:1181	thyroid	1175:1181	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	5	81	located	observed	1124:1131	arg2	levels					1094:1099	high expression levels	1078:1099	high expression levels of MMP20 and DSPP	1078:1117	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	5	81	located	observed	1124:1131	arg2	RESULTS					1056:1062	RESULTS	1056:1062	RESULTS	1056:1062	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	5	81	located	observed	1124:1131	arg1	colon					1158:1162	colon	1158:1162	colon	1158:1162	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	5	81	located	observed	1124:1131	arg1	prostate					1165:1172	prostate	1165:1172	prostate	1165:1172	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	5	81	located	observed	1124:1131	arg1	neoplasms					1197:1205	cervical neoplasms	1188:1205	cervical neoplasms	1188:1205	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	2	82	theme	premalignant	485:496	arg1	lesions					498:504	dysplastic oral premalignant lesions	469:504	dysplastic oral premalignant lesions (OPLs)	469:511	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	82	theme	premalignant	485:496	arg1	OPLs					507:510	OPLs	507:510	OPLs	507:510	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	83	theme	N-linked	385:392	arg1	SIBLINGs					409:416	SIBLINGs	409:416	SIBLINGs	409:416	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	83	theme	N-linked	385:392	arg1	Glycoproteins					394:406	the Small Integrin Binding Ligand N-linked Glycoproteins	351:406	the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	351:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	84	theme	oral	429:432	arg1	carcinoma					448:456	human oral squamous cell carcinoma	423:456	human oral squamous cell carcinoma (OSCC)	423:463	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	84	theme	oral	429:432	arg1	OSCC					459:462	OSCC	459:462	OSCC	459:462	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	85	theme	Binding	370:376	arg1	SIBLINGs					409:416	SIBLINGs	409:416	SIBLINGs	409:416	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	85	theme	Binding	370:376	arg1	Glycoproteins					394:406	the Small Integrin Binding Ligand N-linked Glycoproteins	351:406	the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	351:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	0	86	theme	sialophosphoprotein	17:35	arg1	Survey					0:5	Survey	0:5	Survey of dentin sialophosphoprotein	0:35	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	0	86	theme	sialophosphoprotein	17:35	arg1	metalloproteinase-20					60:79	its cognate matrix metalloproteinase-20	41:79	its cognate matrix metalloproteinase-20 in human cancers	41:96	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	5	87	theme	DSPP	1114:1117	arg1	levels					1094:1099	high expression levels	1078:1099	high expression levels of MMP20 and DSPP	1078:1117	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	1	88	theme	Matrix	110:115	arg1	MMP20					140:144	MMP20	140:144	MMP20	140:144	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	1	88	theme	Matrix	110:115	arg1	metalloproteinases-20					117:137	BACKGROUND Matrix metalloproteinases-20	99:137	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression	99:156	BACKGROUND Matrix metalloproteinases-20 (MMP20) expression is widely regarded as tooth specific, with expression limited to dental hard tissues.
30932369	4	89	theme	MMP20	949:953	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	90	theme	tissue	765:770	arg1	microarrays					772:782	commercially available tissue microarrays	742:782	commercially available tissue microarrays (TMAs)	742:789	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	90	theme	tissue	765:770	arg1	TMAs					785:788	TMAs	785:788	TMAs	785:788	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	9	91	with	cancers	1665:1671	arg1	implications					1704:1715	diagnostic and prognostic implications	1678:1715	diagnostic and prognostic implications	1678:1715	These results suggest MMP20-DSPP pairing as a potential marker of disease activity in some epithelial cancers with diagnostic and prognostic implications.
30932369	0	92	theme	matrix	53:58	arg1	metalloproteinase-20					60:79	its cognate matrix metalloproteinase-20	41:79	its cognate matrix metalloproteinase-20 in human cancers	41:96	Survey of dentin sialophosphoprotein and its cognate matrix metalloproteinase-20 in human cancers.
30932369	3	93	dep	breast	678:683	arg1	the					674:676	the	674:676	the	674:676	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	4	94	theme	DSPP	959:962	arg1	expressions					934:944	the expressions	930:944	the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts	930:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	8	95	theme	other	1548:1552	arg1	cancers					1554:1560	other cancers	1548:1560	other cancers	1548:1560	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	5	96	theme	MMP20	1104:1108	arg1	levels					1094:1099	high expression levels	1078:1099	high expression levels of MMP20 and DSPP	1078:1117	RESULTS Significantly high expression levels of MMP20 and DSPP were observed in the malignant breast, colon, prostate, thyroid, and cervical neoplasms compared with their benign and normal counterparts.
30932369	4	97	from	expressions	934:944	arg1	prostate					986:993	prostate	986:993	prostate	986:993	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	97	from	expressions	934:944	arg1	thyroid					996:1002	thyroid	996:1002	thyroid	996:1002	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	97	from	expressions	934:944	arg1	breast					971:976	breast	971:976	breast	971:976	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	97	from	expressions	934:944	arg1	counterparts					1042:1053	their normal counterparts	1029:1053	their normal counterparts	1029:1053	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	97	from	expressions	934:944	arg1	colon					979:983	colon	979:983	colon	979:983	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	4	97	from	expressions	934:944	arg1	neoplasms					1014:1022	cervical neoplasms	1005:1022	cervical neoplasms	1005:1022	Using commercially available tissue microarrays (TMAs) and cell lines, we performed immunohistochemistry, immunofluorescence, proximity ligation assay, and western blot experiments to determine the expressions of MMP20 and DSPP in the breast, colon, prostate, thyroid, cervical neoplasms, and their normal counterparts.
30932369	8	98	located	present	1537:1543	arg2	CONCLUSIONS					1428:1438	CONCLUSIONS	1428:1438	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers	1428:1531	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	8	98	located	present	1537:1543	arg1	cancers					1554:1560	other cancers	1548:1560	other cancers	1548:1560	CONCLUSIONS The co-localization and potential MMP20-DSPP interaction previously reported in oral cancers are present in other cancers.
30932369	3	99	theme	partner	663:669	arg1	expression					622:631	the expression	618:631	the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms	618:733	METHODS This study aimed to survey the expression of MMP20 and its cognate DSPP partner in the breast, colon, prostate, thyroid, and cervical neoplasms.
30932369	2	100	theme	Small	355:359	arg1	SIBLINGs					409:416	SIBLINGs	409:416	SIBLINGs	409:416	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30932369	2	100	theme	Small	355:359	arg1	Glycoproteins					394:406	the Small Integrin Binding Ligand N-linked Glycoproteins	351:406	the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs)	351:417	Recently, we reported MMP20 expression and interaction with dentin sialophosphoprotein (DSPP), a member of the Small Integrin Binding Ligand N-linked Glycoproteins (SIBLINGs), in human oral squamous cell carcinoma (OSCC) and dysplastic oral premalignant lesions (OPLs), suggesting a role for MMP20-DSPP interaction in oral carcinogenesis.
30712568	7	0	gly	N-glycosylation	1602:1616	arg2	sites					1618:1622	348 unique N-glycosylation sites	1591:1622	348 unique N-glycosylation sites	1591:1622	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	7	0	gly	N-glycosylation	1602:1616	arg2	348					1591:1593	348	1591:1593	348	1591:1593	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	3	1	theme	@	577:577	arg1	PMSA					578:581	Fe3O4@PMSA	572:581	Fe3O4@PMSA	572:581	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	1	2	theme	glycopeptides	321:333	arg1	enrichment					307:316	selective enrichment	297:316	selective enrichment of glycopeptides	297:333	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	7	3	gly	glycopeptides	1632:1644	arg2	glycopeptides					1632:1644	419 glycopeptides	1628:1644	419 glycopeptides from 158 glycoproteins	1628:1667	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	7	3	gly	glycopeptides	1632:1644	arg1	glycoproteins					1655:1667	158 glycoproteins	1651:1667	158 glycoproteins	1651:1667	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	2	4	theme	tedious	347:353	arg1	synthesis					355:363	tedious synthesis	347:363	tedious synthesis	347:363	However, a tedious synthesis and low specificity for glycopeptides have restricted its application.
30712568	5	5	theme	IgG	1260:1262	arg1	selectivity					1142:1152	high selectivity	1137:1152	high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20)	1137:1241	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	5	theme	IgG	1260:1262	arg1	mixture					1249:1255	a mixture	1247:1255	a mixture of IgG and BSA	1247:1270	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	4	6	theme	selective	887:895	arg1	enrichment					897:906	selective enrichment	887:906	selective enrichment of glycopeptides	887:923	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	5	7	dep	1:230	1293:1297	arg1	glycopeptides					1308:1320	sixteen glycopeptides	1300:1320	sixteen glycopeptides identified	1300:1331	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	1	8	theme	solid	247:251	arg1	phase					253:257	solid phase	247:257	solid phase	247:257	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	7	9	gly	glycopeptides	1555:1567	arg2	glycopeptides					1555:1567	N-linked glycopeptides	1546:1567	N-linked glycopeptides from human serum	1546:1584	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	7	9	gly	glycopeptides	1555:1567	arg1	serum					1580:1584	human serum	1574:1584	human serum	1574:1584	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	5	10	theme	Fe3O4	1113:1117	arg1	PMSA					1119:1122	the Fe3O4@PMSA	1109:1122	the Fe3O4@PMSA	1109:1122	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	3	11	theme	-dimethyl-	629:638	arg1	MSA					675:677	MSA	675:677	MSA	675:677	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	11	theme	-dimethyl-	629:638	arg1	hydroxide					664:672	(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide	603:672	(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide	603:672	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	8	12	theme	proposed	1751:1758	arg1	PMSA					1766:1769	the proposed Fe3O4@PMSA	1747:1769	the proposed Fe3O4@PMSA	1747:1769	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	1	13	theme	extensive	273:281	arg1	attention					283:291	extensive attention	273:291	extensive attention	273:291	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	6	14	dep	detection	1358:1366	arg1	limit					1368:1372	limit	1368:1372	limit as low as 0.67 fmol for IgG (S/N ≥ 10) and satisfied recovery yield more than 74%	1368:1454	Besides, the detection limit as low as 0.67 fmol for IgG (S/N ≥ 10) and satisfied recovery yield more than 74% were achieved by the proposed sorbents.
30712568	7	15	theme	unique	1595:1600	arg1	sites					1618:1622	348 unique N-glycosylation sites	1591:1622	348 unique N-glycosylation sites	1591:1622	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	4	16	theme	well-designed	746:758	arg1	composites					760:769	The well-designed composites	742:769	The well-designed composites	742:769	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	5	17	with	molecules	1019:1027	arg1	groups					1057:1062	multi-charge and polar groups	1034:1062	multi-charge and polar groups	1034:1062	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	18	theme	polymer	1092:1098	arg1	coating					1100:1106	resulting polymer coating	1082:1106	resulting polymer coating	1082:1106	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	8	19	theme	@	1765:1765	arg1	PMSA					1766:1769	the proposed Fe3O4@PMSA	1747:1769	the proposed Fe3O4@PMSA	1747:1769	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	1	20	theme	Hydrophilic	158:168	arg1	HILIC					198:202	HILIC	198:202	HILIC	198:202	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	1	20	theme	Hydrophilic	158:168	arg1	chromatography					182:195	Hydrophilic interaction chromatography	158:195	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase	158:257	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	3	21	theme	ammonium	655:662	arg1	MSA					675:677	MSA	675:677	MSA	675:677	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	21	theme	ammonium	655:662	arg1	hydroxide					664:672	(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide	603:672	(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide	603:672	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	22	dep	zwitterion	591:600	arg1	MSA					675:677	MSA	675:677	MSA	675:677	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	22	dep	zwitterion	591:600	arg1	hydroxide					664:672	(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide	603:672	(2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide	603:672	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	0	23	theme	distillation-precipitation	67:92	arg1	polymerization					94:107	one-step distillation-precipitation polymerization	58:107	one-step distillation-precipitation polymerization	58:107	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	5	24	theme	enrichment	1172:1181	arg1	glycopeptides					1158:1170	glycopeptides	1158:1170	glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20)	1158:1241	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	8	25	theme	promising	1780:1788	arg1	potential					1790:1798	a promising potential	1778:1798	a promising potential	1778:1798	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	3	26	dep	2-	604:605	arg1	methacryloyloxy					607:621	methacryloyloxy	607:621	methacryloyloxy	607:621	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	5	27	gly	glycopeptides	1207:1219	arg2	S/N ≥ 20					1233:1240	S/N ≥ 20	1233:1240	S/N ≥ 20	1233:1240	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	27	gly	glycopeptides	1207:1219	arg2	glycopeptides					1207:1219	twenty glycopeptides	1200:1219	twenty glycopeptides identified	1200:1230	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	2	28	dep	synthesis	355:363	arg1	a					345:345	a	345:345	a	345:345	However, a tedious synthesis and low specificity for glycopeptides have restricted its application.
30712568	5	29	theme	IgG	1188:1190	arg1	digest					1192:1197	IgG digest	1188:1197	IgG digest (twenty glycopeptides identified, S/N ≥ 20)	1188:1241	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	7	30	theme	1 μL	1699:1702	arg1	serum					1710:1714	1 μL human serum	1699:1714	1 μL human serum	1699:1714	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	7	31	theme	N-linked	1546:1553	arg1	glycopeptides					1555:1567	N-linked glycopeptides	1546:1567	N-linked glycopeptides from human serum	1546:1584	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	5	32	theme	1:230	1293:1297	arg1	ratio					1284:1288	the mass ratio	1275:1288	the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20)	1275:1342	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	0	33	theme	specific	120:127	arg1	enrichment					129:138	highly specific enrichment	113:138	highly specific enrichment of glycopeptides	113:155	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	5	34	theme	high	1137:1140	arg1	selectivity					1142:1152	high selectivity	1137:1152	high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20)	1137:1241	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	35	theme	molecules	1019:1027	arg1	abundant					1003:1010	abundant	1003:1010	abundant	1003:1010	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	7	36	link	N-linked	1546:1553	arg1	glycopeptides					1555:1567	N-linked glycopeptides	1546:1567	N-linked glycopeptides from human serum	1546:1584	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	4	37	theme	water	836:840	arg1	hydrophilicity					820:833	superior hydrophilicity	811:833	superior hydrophilicity (water contact angle 30.2)	811:860	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	4	37	theme	water	836:840	arg1	angle					850:854	water contact angle 30.2	836:859	water contact angle 30.2	836:859	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	3	38	theme	zwitterionic	506:517	arg1	composites					549:558	a zwitterionic (ZIC) polymer-coated magnetic composites	504:558	a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA)	504:582	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	0	39	theme	composites	44:53	arg1	fabrication					7:17	Facile fabrication	0:17	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.	0:156	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	1	40	gly	glycopeptides	321:333	arg2	glycopeptides					321:333	glycopeptides	321:333	glycopeptides	321:333	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	5	41	theme	multi-charge	1034:1045	arg1	groups					1057:1062	multi-charge and polar groups	1034:1062	multi-charge and polar groups	1034:1062	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	4	42	theme	ZIC-polymer	789:799	arg1	shell					801:805	ZIC-polymer shell	789:805	ZIC-polymer shell	789:805	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	0	43	theme	Facile	0:5	arg1	fabrication					7:17	Facile fabrication	0:17	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.	0:156	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	8	44	theme	samples	1847:1853	arg1	analysis					1819:1826	glycoproteomics analysis	1803:1826	glycoproteomics analysis of real biological samples	1803:1853	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	5	45	dep	digest	1192:1197	arg1	glycopeptides					1207:1219	twenty glycopeptides	1200:1219	twenty glycopeptides identified	1200:1230	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	45	dep	digest	1192:1197	arg1	S/N ≥ 20					1233:1240	S/N ≥ 20	1233:1240	S/N ≥ 20	1233:1240	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	3	46	theme	polymer-coated	525:538	arg1	composites					549:558	a zwitterionic (ZIC) polymer-coated magnetic composites	504:558	a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA)	504:582	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	6	47	theme	recovery	1427:1434	arg1	yield					1436:1440	satisfied recovery yield	1417:1440	satisfied recovery yield more than 74%	1417:1454	Besides, the detection limit as low as 0.67 fmol for IgG (S/N ≥ 10) and satisfied recovery yield more than 74% were achieved by the proposed sorbents.
30712568	0	48	gly	glycopeptides	143:155	arg2	glycopeptides					143:155	glycopeptides	143:155	glycopeptides	143:155	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	3	49	theme	ZIC	520:522	arg1	composites					549:558	a zwitterionic (ZIC) polymer-coated magnetic composites	504:558	a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA)	504:582	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	1	50	theme	zwitterion-modified	215:233	arg1	material					235:242	zwitterion-modified material	215:242	zwitterion-modified material	215:242	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	0	51	theme	magnetic	35:42	arg1	composites					44:53	zwitterionic magnetic composites	22:53	zwitterionic magnetic composites	22:53	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	7	52	theme	Fe3O4	1509:1513	arg1	PMSA					1515:1518	the Fe3O4@PMSA	1505:1518	the Fe3O4@PMSA	1505:1518	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	6	53	dep	%	1454:1454	arg1	74					1452:1453	74	1452:1453	74	1452:1453	Besides, the detection limit as low as 0.67 fmol for IgG (S/N ≥ 10) and satisfied recovery yield more than 74% were achieved by the proposed sorbents.
30712568	5	54	gly	glycopeptides	1308:1320	arg2	glycopeptides					1308:1320	sixteen glycopeptides	1300:1320	sixteen glycopeptides identified	1300:1331	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	55	theme	resulting	1082:1090	arg1	coating					1100:1106	resulting polymer coating	1082:1106	resulting polymer coating	1082:1106	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	2	56	gly	glycopeptides	389:401	arg2	glycopeptides					389:401	glycopeptides	389:401	glycopeptides	389:401	However, a tedious synthesis and low specificity for glycopeptides have restricted its application.
30712568	6	57	theme	proposed	1477:1484	arg1	sorbents					1486:1493	the proposed sorbents	1473:1493	the proposed sorbents	1473:1493	Besides, the detection limit as low as 0.67 fmol for IgG (S/N ≥ 10) and satisfied recovery yield more than 74% were achieved by the proposed sorbents.
30712568	7	58	from	serum	1580:1584	arg1	glycopeptides					1555:1567	N-linked glycopeptides	1546:1567	N-linked glycopeptides from human serum	1546:1584	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	5	59	theme	polar	1051:1055	arg1	groups					1057:1062	multi-charge and polar groups	1034:1062	multi-charge and polar groups	1034:1062	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	3	60	theme	one-step	684:691	arg1	DPP					736:738	DPP	736:738	DPP	736:738	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	60	theme	one-step	684:691	arg1	polymerization					720:733	one-step distillation-precipitation polymerization	684:733	one-step distillation-precipitation polymerization (DPP)	684:739	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	1	61	theme	selective	297:305	arg1	enrichment					307:316	selective enrichment	297:316	selective enrichment of glycopeptides	297:333	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	7	62	gly	glycoproteins	1655:1667	arg1	glycoproteins					1655:1667	158 glycoproteins	1651:1667	158 glycoproteins	1651:1667	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	3	63	theme	Fe3O4	572:576	arg1	PMSA					578:581	Fe3O4@PMSA	572:581	Fe3O4@PMSA	572:581	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	4	64	theme	glycopeptides	911:923	arg1	enrichment					897:906	selective enrichment	887:906	selective enrichment of glycopeptides	887:923	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	5	65	dep	glycopeptides	1308:1320	arg1	S/N ≥ 20					1334:1341	S/N ≥ 20	1334:1341	S/N ≥ 20	1334:1341	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	4	66	gly	glycopeptides	911:923	arg2	glycopeptides					911:923	glycopeptides	911:923	glycopeptides	911:923	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	2	67	theme	low	369:371	arg1	specificity					373:383	low specificity	369:383	low specificity	369:383	However, a tedious synthesis and low specificity for glycopeptides have restricted its application.
30712568	7	68	theme	N-glycosylation	1602:1616	arg1	sites					1618:1622	348 unique N-glycosylation sites	1591:1622	348 unique N-glycosylation sites	1591:1622	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	5	69	gly	glycopeptides	1158:1170	arg2	glycopeptides					1158:1170	glycopeptides	1158:1170	glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20)	1158:1241	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	70	theme	@	1118:1118	arg1	PMSA					1119:1122	the Fe3O4@PMSA	1109:1122	the Fe3O4@PMSA	1109:1122	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	3	71	dep	-dimethyl-	629:638	arg1	3-sulfopropyl					640:652	3-sulfopropyl	640:652	3-sulfopropyl	640:652	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	71	dep	-dimethyl-	629:638	arg1	ethyl					623:627	2-(methacryloyloxy)ethyl	604:627	2-(methacryloyloxy)ethyl	604:627	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	4	72	theme	standard	948:955	arg1	samples					966:972	standard and real samples	948:972	standard and real samples	948:972	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	7	73	from	glycoproteins	1655:1667	arg1	sites					1618:1622	348 unique N-glycosylation sites	1591:1622	348 unique N-glycosylation sites	1591:1622	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	7	73	from	glycoproteins	1655:1667	arg1	glycopeptides					1632:1644	419 glycopeptides	1628:1644	419 glycopeptides from 158 glycoproteins	1628:1667	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	5	74	theme	coating	1100:1106	arg1	surface					1071:1077	the surface	1067:1077	the surface of resulting polymer coating	1067:1106	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	8	75	theme	Fe3O4	1760:1764	arg1	PMSA					1766:1769	the proposed Fe3O4@PMSA	1747:1769	the proposed Fe3O4@PMSA	1747:1769	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	1	76	theme	interaction	170:180	arg1	HILIC					198:202	HILIC	198:202	HILIC	198:202	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	1	76	theme	interaction	170:180	arg1	chromatography					182:195	Hydrophilic interaction chromatography	158:195	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase	158:257	Hydrophilic interaction chromatography (HILIC) utilizing zwitterion-modified material as solid phase has attracted extensive attention for selective enrichment of glycopeptides.
30712568	7	77	theme	human	1574:1578	arg1	serum					1580:1584	human serum	1574:1584	human serum	1574:1584	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	4	78	theme	real	961:964	arg1	samples					966:972	standard and real samples	948:972	standard and real samples	948:972	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	5	79	theme	ZIC	1015:1017	arg1	molecules					1019:1027	ZIC molecules	1015:1027	ZIC molecules with multi-charge and polar groups	1015:1062	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	80	theme	mass	1279:1282	arg1	ratio					1284:1288	the mass ratio	1275:1288	the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20)	1275:1342	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	81	with	enrichment	1172:1181	arg1	digest					1192:1197	IgG digest	1188:1197	IgG digest (twenty glycopeptides identified, S/N ≥ 20)	1188:1241	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	3	82	dep	composites	549:558	arg1	denoted					561:567	denoted	561:567	denoted as Fe3O4@PMSA	561:581	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	7	83	theme	human	1704:1708	arg1	serum					1710:1714	1 μL human serum	1699:1714	1 μL human serum	1699:1714	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	4	84	theme	superior	811:818	arg1	hydrophilicity					820:833	superior hydrophilicity	811:833	superior hydrophilicity (water contact angle 30.2)	811:860	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	4	84	theme	superior	811:818	arg1	angle					850:854	water contact angle 30.2	836:859	water contact angle 30.2	836:859	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	0	85	theme	glycopeptides	143:155	arg1	enrichment					129:138	highly specific enrichment	113:138	highly specific enrichment of glycopeptides	113:155	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	8	86	theme	glycoproteomics	1803:1817	arg1	analysis					1819:1826	glycoproteomics analysis	1803:1826	glycoproteomics analysis of real biological samples	1803:1853	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	3	87	theme	effective	457:465	arg1	approach					467:474	a facile and effective approach	444:474	a facile and effective approach	444:474	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	0	88	theme	zwitterionic	22:33	arg1	composites					44:53	zwitterionic magnetic composites	22:53	zwitterionic magnetic composites	22:53	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	8	89	theme	biological	1836:1845	arg1	samples					1847:1853	real biological samples	1831:1853	real biological samples	1831:1853	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	3	90	theme	facile	446:451	arg1	approach					467:474	a facile and effective approach	444:474	a facile and effective approach	444:474	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	91	theme	magnetic	540:547	arg1	composites					549:558	a zwitterionic (ZIC) polymer-coated magnetic composites	504:558	a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA)	504:582	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	6	92	theme	satisfied	1417:1425	arg1	yield					1436:1440	satisfied recovery yield	1417:1440	satisfied recovery yield more than 74%	1417:1454	Besides, the detection limit as low as 0.67 fmol for IgG (S/N ≥ 10) and satisfied recovery yield more than 74% were achieved by the proposed sorbents.
30712568	0	93	theme	one-step	58:65	arg1	polymerization					94:107	one-step distillation-precipitation polymerization	58:107	one-step distillation-precipitation polymerization	58:107	Facile fabrication of zwitterionic magnetic composites by one-step distillation-precipitation polymerization for highly specific enrichment of glycopeptides.
30712568	6	94	dep	yield	1436:1440	arg1	%					1454:1454	%	1454:1454	%	1454:1454	Besides, the detection limit as low as 0.67 fmol for IgG (S/N ≥ 10) and satisfied recovery yield more than 74% were achieved by the proposed sorbents.
30712568	7	95	theme	@	1514:1514	arg1	PMSA					1515:1518	the Fe3O4@PMSA	1505:1518	the Fe3O4@PMSA	1505:1518	Finally, the Fe3O4@PMSA was applied for enriching N-linked glycopeptides from human serum, and 348 unique N-glycosylation sites and 419 glycopeptides from 158 glycoproteins were strictly identified from 1 μL human serum.
30712568	3	96	theme	distillation-precipitation	693:718	arg1	DPP					736:738	DPP	736:738	DPP	736:738	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	3	96	theme	distillation-precipitation	693:718	arg1	polymerization					720:733	one-step distillation-precipitation polymerization	684:733	one-step distillation-precipitation polymerization (DPP)	684:739	Herein, a facile and effective approach was developed to synthesize a zwitterionic (ZIC) polymer-coated magnetic composites (denoted as Fe3O4@PMSA) with a zwitterion ((2-(methacryloyloxy)ethyl)-dimethyl-(3-sulfopropyl) ammonium hydroxide, MSA) via one-step distillation-precipitation polymerization (DPP).
30712568	8	97	theme	real	1831:1834	arg1	samples					1847:1853	real biological samples	1831:1853	real biological samples	1831:1853	The results demonstrated that the proposed Fe3O4@PMSA showed a promising potential in glycoproteomics analysis of real biological samples.
30712568	4	98	theme	contact	842:848	arg1	hydrophilicity					820:833	superior hydrophilicity	811:833	superior hydrophilicity (water contact angle 30.2)	811:860	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	4	98	theme	contact	842:848	arg1	angle					850:854	water contact angle 30.2	836:859	water contact angle 30.2	836:859	The well-designed composites presented clearly ZIC-polymer shell and superior hydrophilicity (water contact angle 30.2), and the performance for selective enrichment of glycopeptides were investigated with standard and real samples, respectively.
30712568	5	99	theme	BSA	1268:1270	arg1	selectivity					1142:1152	high selectivity	1137:1152	high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20)	1137:1241	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
30712568	5	99	theme	BSA	1268:1270	arg1	mixture					1249:1255	a mixture	1247:1255	a mixture of IgG and BSA	1247:1270	Owning to the abundant of ZIC molecules with multi-charge and polar groups on the surface of resulting polymer coating, the Fe3O4@PMSA demonstrated high selectivity for glycopeptides enrichment with IgG digest (twenty glycopeptides identified, S/N ≥ 20) and a mixture of IgG and BSA at the mass ratio of 1:230 (sixteen glycopeptides identified, S/N ≥ 20).
29596379	4	0	contain	possesses	632:640	arg2	motif					797:801	a conserved transport motif	775:801	a conserved transport motif	775:801	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	0	contain	possesses	632:640	arg1	maNRAMP					623:629	maNRAMP	623:629	maNRAMP	623:629	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	0	contain	possesses	632:640	arg2	features					665:672	the typical structural features	642:672	the typical structural features	642:672	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	0	contain	possesses	632:640	arg2	domains					726:732	12 transmembrane domains	709:732	12 transmembrane domains	709:732	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	0	contain	possesses	632:640	arg1	protein					614:620	The deduced protein	602:620	The deduced protein (maNRAMP)	602:630	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	0	contain	possesses	632:640	arg2	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	7	1	from	Nramp1	1449:1454	arg1	function					1459:1466	function	1459:1466	function	1459:1466	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	1	2	theme	protein	173:179	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	2	theme	protein	173:179	arg1	one					218:220	one	218:220	one	218:220	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	2	theme	protein	173:179	arg1	Nramp					187:191	Nramp	187:191	Nramp	187:191	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	2	theme	protein	173:179	arg1	gene					181:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	5	3	theme	significant	859:869	arg1	consistency					880:890	the significant sequence consistency	855:890	the significant sequence consistency	855:890	Phylogenetic analysis revealed that maNRAMP shares the significant sequence consistency with other teleosts, and shows the higher sequence similarity to mammalian Nramp2 than Nramp1.
29596379	1	4	theme	candidate	241:249	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	2	5	dep	bream	444:448	arg1	blunt					432:436	blunt	432:436	blunt	432:436	Here, we identified and characterized a new Nramp family member, named as maNramp, in the blunt snout bream.
29596379	5	6	theme	Phylogenetic	804:815	arg1	analysis					817:824	Phylogenetic analysis	804:824	Phylogenetic analysis	804:824	Phylogenetic analysis revealed that maNRAMP shares the significant sequence consistency with other teleosts, and shows the higher sequence similarity to mammalian Nramp2 than Nramp1.
29596379	1	7	theme	genes	251:255	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	7	theme	genes	251:255	arg1	one					218:220	one	218:220	one	218:220	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	7	theme	genes	251:255	arg1	gene					181:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	0	8	theme	Bream	95:99	arg1	Response					71:78	Immune Response	64:78	Immune Response of Blunt Snout Bream	64:99	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	4	9	theme	family	691:696	arg1	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	9	theme	family	691:696	arg1	domains					726:732	12 transmembrane domains	709:732	12 transmembrane domains	709:732	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	9	theme	family	691:696	arg1	motif					797:801	a conserved transport motif	775:801	a conserved transport motif	775:801	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	9	theme	family	691:696	arg1	features					665:672	the typical structural features	642:672	the typical structural features	642:672	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	10	theme	transport	787:795	arg1	motif					797:801	a conserved transport motif	775:801	a conserved transport motif	775:801	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	3	11	theme	153	497:499	arg1	bp					501:502	bp	501:502	bp	501:502	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	4	12	theme	typical	646:652	arg1	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	12	theme	typical	646:652	arg1	domains					726:732	12 transmembrane domains	709:732	12 transmembrane domains	709:732	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	12	theme	typical	646:652	arg1	motif					797:801	a conserved transport motif	775:801	a conserved transport motif	775:801	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	12	theme	typical	646:652	arg1	features					665:672	the typical structural features	642:672	the typical structural features	642:672	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	1	13	theme	responsible	257:267	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	0	14	theme	Snout	89:93	arg1	Bream					95:99	Blunt Snout Bream	83:99	Blunt Snout Bream	83:99	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	4	15	theme	conserved	777:785	arg1	motif					797:801	a conserved transport motif	775:801	a conserved transport motif	775:801	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	16	theme	deduced	606:612	arg1	maNRAMP					623:629	maNRAMP	623:629	maNRAMP	623:629	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	16	theme	deduced	606:612	arg1	protein					614:620	The deduced protein	602:620	The deduced protein (maNRAMP)	602:630	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	7	17	theme	innate	1408:1413	arg1	immunity					1415:1422	fish innate immunity	1403:1422	fish innate immunity	1403:1422	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	3	18	dep	5	504:504	arg1	UTR					506:508	UTR	506:508	UTR	506:508	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	3	18	dep	5	504:504	arg1	bp					592:593	a 1359 bp 3	585:595	a 1359 bp 3	585:595	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	3	18	dep	5	504:504	arg1	frame					534:538	a 1635 bp open reading frame	511:538	a 1635 bp open reading frame encoding a protein with 544 amino acids	511:578	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	4	19	theme	glycosylation	750:762	arg1	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	3	20	theme	full-length	455:465	arg1	cDNA					467:470	The full-length cDNA	451:470	The full-length cDNA of maNramp	451:481	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	0	21	dep	Bream	95:99	arg1	Blunt					83:87	Blunt	83:87	Blunt	83:87	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	6	22	from	abundance	1083:1091	arg1	gill					1185:1188	gill	1185:1188	gill	1185:1188	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	6	22	from	abundance	1083:1091	arg1	kidney					1195:1200	kidney	1195:1200	kidney	1195:1200	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	6	22	from	abundance	1083:1091	arg1	muscle					1177:1182	the muscle	1173:1182	the muscle	1173:1182	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	6	22	from	abundance	1083:1091	arg1	spleen					1100:1105	the spleen	1096:1105	the spleen	1096:1105	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	7	23	theme	lipopolysaccharide	1209:1226	arg1	stimulation					1234:1244	lipopolysaccharide (LPS) stimulation	1209:1244	lipopolysaccharide (LPS) stimulation	1209:1244	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	7	24	theme	peak	1315:1318	arg1	level					1320:1324	a peak level	1313:1324	a peak level	1313:1324	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	4	25	theme	N-linked	741:748	arg1	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	26	theme	NRAMP	677:681	arg1	family					691:696	NRAMP protein family	677:696	NRAMP protein family	677:696	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	2	27	theme	snout	438:442	arg1	bream					444:448	the blunt snout bream	428:448	the blunt snout bream	428:448	Here, we identified and characterized a new Nramp family member, named as maNramp, in the blunt snout bream.
29596379	6	28	theme	highest	1075:1081	arg1	abundance					1083:1091	the highest abundance	1071:1091	the highest abundance in the spleen, followed by the head kidney and intestine,	1071:1149	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	3	29	theme	bp	518:519	arg1	frame					534:538	a 1635 bp open reading frame	511:538	a 1635 bp open reading frame encoding a protein with 544 amino acids	511:578	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	2	30	theme	family	392:397	arg1	member					399:404	a new Nramp family member	380:404	a new Nramp family member	380:404	Here, we identified and characterized a new Nramp family member, named as maNramp, in the blunt snout bream.
29596379	0	31	theme	Natural	0:6	arg1	Protein					41:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	7	32	dep	h.	1331:1332	arg1	indicated					1360:1368	indicated	1360:1368	indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function	1360:1466	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	3	33	theme	open	521:524	arg1	frame					534:538	a 1635 bp open reading frame	511:538	a 1635 bp open reading frame encoding a protein with 544 amino acids	511:578	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	2	34	theme	Nramp	386:390	arg1	member					399:404	a new Nramp family member	380:404	a new Nramp family member	380:404	Here, we identified and characterized a new Nramp family member, named as maNramp, in the blunt snout bream.
29596379	0	35	theme	Macrophage	30:39	arg1	Protein					41:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	1	36	theme	vertebrate	284:293	arg1	resistance					303:312	vertebrate natural resistance	284:312	vertebrate natural resistance to intracellular pathogens	284:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	5	37	theme	mammalian	957:965	arg1	Nramp2					967:972	mammalian Nramp2	957:972	mammalian Nramp2	957:972	Phylogenetic analysis revealed that maNRAMP shares the significant sequence consistency with other teleosts, and shows the higher sequence similarity to mammalian Nramp2 than Nramp1.
29596379	4	38	theme	structural	654:663	arg1	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	38	theme	structural	654:663	arg1	domains					726:732	12 transmembrane domains	709:732	12 transmembrane domains	709:732	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	38	theme	structural	654:663	arg1	motif					797:801	a conserved transport motif	775:801	a conserved transport motif	775:801	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	38	theme	structural	654:663	arg1	features					665:672	the typical structural features	642:672	the typical structural features	642:672	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	0	39	theme	Associated	19:28	arg1	Protein					41:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	1	40	theme	natural	295:301	arg1	resistance					303:312	vertebrate natural resistance	284:312	vertebrate natural resistance to intracellular pathogens	284:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	3	41	theme	5	504:504	arg1	UTR					597:599	a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR	495:599	a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR	495:599	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	3	42	theme	1635	513:516	arg1	bp					518:519	bp	518:519	bp	518:519	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	2	43	theme	new	382:384	arg1	member					399:404	a new Nramp family member	380:404	a new Nramp family member	380:404	Here, we identified and characterized a new Nramp family member, named as maNramp, in the blunt snout bream.
29596379	6	44	from	abundance	1160:1168	arg1	gill					1185:1188	gill	1185:1188	gill	1185:1188	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	6	44	from	abundance	1160:1168	arg1	kidney					1195:1200	kidney	1195:1200	kidney	1195:1200	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	6	44	from	abundance	1160:1168	arg1	muscle					1177:1182	the muscle	1173:1182	the muscle	1173:1182	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	6	44	from	abundance	1160:1168	arg1	spleen					1100:1105	the spleen	1096:1105	the spleen	1096:1105	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	5	45	theme	sequence	934:941	arg1	similarity					943:952	the higher sequence similarity	923:952	the higher sequence similarity to mammalian Nramp2	923:972	Phylogenetic analysis revealed that maNRAMP shares the significant sequence consistency with other teleosts, and shows the higher sequence similarity to mammalian Nramp2 than Nramp1.
29596379	6	46	theme	less	1155:1158	arg1	abundance					1160:1168	less abundance	1155:1168	less abundance in the muscle, gill, and kidney	1155:1200	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	7	47	theme	maNramp	1265:1271	arg1	level					1256:1260	the mRNA level	1247:1260	the mRNA level of maNramp	1247:1271	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	4	48	theme	transmembrane	712:724	arg1	domains					726:732	12 transmembrane domains	709:732	12 transmembrane domains	709:732	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	7	49	theme	mRNA	1251:1254	arg1	level					1256:1260	the mRNA level	1247:1260	the mRNA level of maNramp	1247:1271	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	1	50	theme	intracellular	317:329	arg1	pathogens					331:339	intracellular pathogens	317:339	intracellular pathogens	317:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	4	51	gly	glycosylation	750:762	arg2	three					735:739	three	735:739	three	735:739	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	4	51	gly	glycosylation	750:762	arg2	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	3	52	theme	reading	526:532	arg1	frame					534:538	a 1635 bp open reading frame	511:538	a 1635 bp open reading frame encoding a protein with 544 amino acids	511:578	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	3	53	theme	maNramp	475:481	arg1	cDNA					467:470	The full-length cDNA	451:470	The full-length cDNA of maNramp	451:481	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	4	54	link	N-linked	741:748	arg1	sites					764:768	three N-linked glycosylation sites	735:768	three N-linked glycosylation sites	735:768	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	1	55	theme	macrophage	162:171	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	55	theme	macrophage	162:171	arg1	one					218:220	one	218:220	one	218:220	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	55	theme	macrophage	162:171	arg1	Nramp					187:191	Nramp	187:191	Nramp	187:191	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	55	theme	macrophage	162:171	arg1	gene					181:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	6	56	theme	head	1124:1127	arg1	kidney					1129:1134	the head kidney	1120:1134	the head kidney	1120:1134	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	2	57	from	member	399:404	arg1	bream					444:448	the blunt snout bream	428:448	the blunt snout bream	428:448	Here, we identified and characterized a new Nramp family member, named as maNramp, in the blunt snout bream.
29596379	6	58	theme	normal	1043:1048	arg1	tissues					1050:1056	all normal tissues	1039:1056	all normal tissues tested	1039:1063	It was found that maNramp expressed ubiquitously in all normal tissues tested, with the highest abundance in the spleen, followed by the head kidney and intestine, and less abundance in the muscle, gill, and kidney.
29596379	5	59	theme	sequence	871:878	arg1	consistency					880:890	the significant sequence consistency	855:890	the significant sequence consistency	855:890	Phylogenetic analysis revealed that maNRAMP shares the significant sequence consistency with other teleosts, and shows the higher sequence similarity to mammalian Nramp2 than Nramp1.
29596379	7	60	theme	mammalian	1439:1447	arg1	Nramp1					1449:1454	mammalian Nramp1	1439:1454	mammalian Nramp1 in function	1439:1466	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	4	61	theme	protein	683:689	arg1	family					691:696	NRAMP protein family	677:696	NRAMP protein family	677:696	The deduced protein (maNRAMP) possesses the typical structural features of NRAMP protein family, including 12 transmembrane domains, three N-linked glycosylation sites, and a conserved transport motif.
29596379	3	62	theme	amino	568:572	arg1	acids					574:578	544 amino acids	564:578	544 amino acids	564:578	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	7	63	theme	fish	1403:1406	arg1	immunity					1415:1422	fish innate immunity	1403:1422	fish innate immunity	1403:1422	After lipopolysaccharide (LPS) stimulation, the mRNA level of maNramp was rapidly up-regulated, which reached a peak level at 6 h. Altogether, these results indicated that maNramp might be related to fish innate immunity and similar to mammalian Nramp1 in function.
29596379	1	64	theme	natural	132:138	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	64	theme	natural	132:138	arg1	one					218:220	one	218:220	one	218:220	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	64	theme	natural	132:138	arg1	Nramp					187:191	Nramp	187:191	Nramp	187:191	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	64	theme	natural	132:138	arg1	gene					181:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	3	65	with	protein	551:557	arg1	acids					574:578	544 amino acids	564:578	544 amino acids	564:578	The full-length cDNA of maNramp consists of a 153 bp 5'UTR, a 1635 bp open reading frame encoding a protein with 544 amino acids, and a 1359 bp 3'UTR.
29596379	1	66	theme	resistance-associated	140:160	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	66	theme	resistance-associated	140:160	arg1	one					218:220	one	218:220	one	218:220	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	66	theme	resistance-associated	140:160	arg1	Nramp					187:191	Nramp	187:191	Nramp	187:191	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	1	66	theme	resistance-associated	140:160	arg1	gene					181:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene	128:184	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29596379	0	67	theme	Immune	64:69	arg1	Response					71:78	Immune Response	64:78	Immune Response of Blunt Snout Bream	64:99	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	5	68	theme	other	897:901	arg1	teleosts					903:910	other teleosts	897:910	other teleosts	897:910	Phylogenetic analysis revealed that maNRAMP shares the significant sequence consistency with other teleosts, and shows the higher sequence similarity to mammalian Nramp2 than Nramp1.
29596379	5	69	theme	higher	927:932	arg1	similarity					943:952	the higher sequence similarity	923:952	the higher sequence similarity to mammalian Nramp2	923:972	Phylogenetic analysis revealed that maNRAMP shares the significant sequence consistency with other teleosts, and shows the higher sequence similarity to mammalian Nramp2 than Nramp1.
29596379	0	70	theme	Resistance	8:17	arg1	Protein					41:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein	0:47	Natural Resistance Associated Macrophage Protein Is Involved in Immune Response of Blunt Snout Bream, Megalobrama amblycephala.
29596379	1	71	theme	significant	229:239	arg1	genes					251:255	the significant candidate genes	225:255	the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens	225:339	The natural resistance-associated macrophage protein gene (Nramp), has been identified as one of the significant candidate genes responsible for modulating vertebrate natural resistance to intracellular pathogens.
29648826	5	0	dep	t	769:769	arg1	t					813:813	AUC0- t	807:813	AUC0- t	807:813	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	5	1	theme	oral	833:836	arg1	bioavailability					838:852	a calculated oral bioavailability	820:852	a calculated oral bioavailability of 52%	820:859	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	5	2	from	t	769:769	arg1	brain					801:805	brain	801:805	brain	801:805	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	6	3	theme	higher	973:978	arg1	t					993:993	a 3.8-fold higher plasma AUC0- t	962:993	a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41%	962:1026	In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C.
29648826	7	4	with	prodrug	1088:1094	arg1	properties					1131:1140	better physicochemical properties	1108:1140	better physicochemical properties	1108:1140	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	7	4	with	prodrug	1088:1094	arg1	bioavailability					1155:1169	enhanced bioavailability	1146:1169	enhanced bioavailability in both mice and dog	1146:1190	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	4	5	theme	oxy	622:624	arg1	promoiety					633:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	5	theme	oxy	622:624	arg1	phosphoryl					611:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	6	6	dep	showed	955:960	arg1	compared					1028:1035	compared	1028:1035	showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C	955:1052	In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C.
29648826	0	7	from	Solubility	63:72	arg1	Dogs					111:114	Dogs	111:114	Dogs	111:114	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	0	7	from	Solubility	63:72	arg1	Mice					102:105	Mice	102:105	Mice	102:105	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	7	8	from	bioavailability	1155:1169	arg1	dog					1188:1190	dog	1188:1190	dog	1188:1190	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	7	8	from	bioavailability	1155:1169	arg1	mice					1179:1182	mice	1179:1182	mice	1179:1182	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	6	9	theme	plasma	980:985	arg1	t					993:993	a 3.8-fold higher plasma AUC0- t	962:993	a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41%	962:1026	In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C.
29648826	7	10	theme	physicochemical	1115:1129	arg1	properties					1131:1140	better physicochemical properties	1108:1140	better physicochemical properties	1108:1140	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	5	11	theme	MBZ-polymorph	885:897	arg1	MBZ-C					902:906	MBZ-C	902:906	MBZ-C	902:906	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	5	11	theme	MBZ-polymorph	885:897	arg1	C					899:899	MBZ-polymorph C	885:899	MBZ-polymorph C (MBZ-C)	885:907	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	5	12	theme	%	859:859	arg1	bioavailability					838:852	a calculated oral bioavailability	820:852	a calculated oral bioavailability of 52%	820:859	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	1	13	theme	broad-spectrum	154:167	arg1	Mebendazole					117:127	Mebendazole (MBZ)	117:133	Mebendazole (MBZ)	117:133	Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent.
29648826	1	13	theme	broad-spectrum	154:167	arg1	anthelmintic					169:180	a broad-spectrum anthelmintic	152:180	a broad-spectrum anthelmintic	152:180	Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent.
29648826	5	14	theme	higher	749:754	arg1	t					769:769	a 2.2-fold higher plasma AUC0- t	738:769	a 2.2-fold higher plasma AUC0- t	738:769	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	6	15	with	t	993:993	arg1	bioavailability					1005:1019	oral bioavailability	1000:1019	oral bioavailability of 41%	1000:1026	In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C.
29648826	0	16	theme	Improved	46:53	arg1	Solubility					63:72	Improved Aqueous Solubility	46:72	Improved Aqueous Solubility	46:72	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	5	17	theme	plasma	756:761	arg1	t					769:769	a 2.2-fold higher plasma AUC0- t	738:769	a 2.2-fold higher plasma AUC0- t	738:769	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	3	18	link	N-linked	402:409	arg1	aminoacyloxymethyl					448:465	aminoacyloxymethyl	448:465	aminoacyloxymethyl	448:465	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	18	link	N-linked	402:409	arg1	acyloxymethyl					433:445	acyloxymethyl	433:445	acyloxymethyl	433:445	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	18	link	N-linked	402:409	arg1	promoieties					411:421	various N-linked promoieties	394:421	various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics	394:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	18	link	N-linked	402:409	arg1	phosphonooxymethyl					484:501	substituted phosphonooxymethyl	472:501	substituted phosphonooxymethyl in attempt to improve these characteristics	472:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	4	19	contain	containing	561:570	arg2	promoiety					633:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	19	contain	containing	561:570	arg1	Compound					548:555	Compound 12	548:558	Compound 12	548:558	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	19	contain	containing	561:570	arg2	phosphoryl					611:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	20	theme	methyl	626:631	arg1	promoiety					633:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	20	theme	methyl	626:631	arg1	phosphoryl					611:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	0	21	theme	N-Substituted	0:12	arg1	Prodrugs					14:21	N-Substituted Prodrugs	0:21	N-Substituted Prodrugs of Mebendazole	0:36	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	7	22	from	properties	1131:1140	arg1	dog					1188:1190	dog	1188:1190	dog	1188:1190	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	7	22	from	properties	1131:1140	arg1	mice					1179:1182	mice	1179:1182	mice	1179:1182	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	3	23	theme	various	394:400	arg1	aminoacyloxymethyl					448:465	aminoacyloxymethyl	448:465	aminoacyloxymethyl	448:465	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	23	theme	various	394:400	arg1	acyloxymethyl					433:445	acyloxymethyl	433:445	acyloxymethyl	433:445	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	23	theme	various	394:400	arg1	promoieties					411:421	various N-linked promoieties	394:421	various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics	394:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	23	theme	various	394:400	arg1	phosphonooxymethyl					484:501	substituted phosphonooxymethyl	472:501	substituted phosphonooxymethyl in attempt to improve these characteristics	472:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	0	24	theme	Mebendazole	26:36	arg1	Prodrugs					14:21	N-Substituted Prodrugs	0:21	N-Substituted Prodrugs of Mebendazole	0:36	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	3	25	from	phosphonooxymethyl	484:501	arg1	attempt					506:512	attempt	506:512	attempt to improve these characteristics	506:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	6	26	theme	%	1026:1026	arg1	bioavailability					1005:1019	oral bioavailability	1000:1019	oral bioavailability of 41%	1000:1026	In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C.
29648826	4	27	theme	methoxy	603:609	arg1	isopropoxycarbonyl					580:597	isopropoxycarbonyl	580:597	isopropoxycarbonyl	580:597	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	27	theme	methoxy	603:609	arg1	promoiety					633:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	27	theme	methoxy	603:609	arg1	phosphoryl					611:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	5	28	theme	1.7-fold	777:784	arg1	improvement					786:796	a 1.7-fold improvement	775:796	a 1.7-fold improvement in brain	775:805	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	3	29	theme	prodrug	372:378	arg1	approach					380:387	a prodrug approach	370:387	a prodrug approach	370:387	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	4	30	theme	>10 000-fold	653:664	arg1	improvement					666:676	a >10 000-fold improvement	651:676	a >10 000-fold improvement in aqueous solubility	651:698	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	0	31	from	Bioavailability	83:97	arg1	Dogs					111:114	Dogs	111:114	Dogs	111:114	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	0	31	from	Bioavailability	83:97	arg1	Mice					102:105	Mice	102:105	Mice	102:105	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	7	32	theme	enhanced	1146:1153	arg1	bioavailability					1155:1169	enhanced bioavailability	1146:1169	enhanced bioavailability in both mice and dog	1146:1190	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	3	33	theme	N-linked	402:409	arg1	aminoacyloxymethyl					448:465	aminoacyloxymethyl	448:465	aminoacyloxymethyl	448:465	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	33	theme	N-linked	402:409	arg1	acyloxymethyl					433:445	acyloxymethyl	433:445	acyloxymethyl	433:445	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	33	theme	N-linked	402:409	arg1	promoieties					411:421	various N-linked promoieties	394:421	various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics	394:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	33	theme	N-linked	402:409	arg1	phosphonooxymethyl					484:501	substituted phosphonooxymethyl	472:501	substituted phosphonooxymethyl in attempt to improve these characteristics	472:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	6	34	theme	oral	1000:1003	arg1	bioavailability					1005:1019	oral bioavailability	1000:1019	oral bioavailability of 41%	1000:1026	In dogs, 12 showed a 3.8-fold higher plasma AUC0- t with oral bioavailability of 41% compared to 11% for MBZ-C.
29648826	5	35	from	improvement	786:796	arg1	brain					801:805	brain	801:805	brain	801:805	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	5	36	theme	bioavailable	919:930	arg1	%					879:879	24%	877:879	24% for MBZ-polymorph C (MBZ-C)	877:907	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	5	36	theme	bioavailable	919:930	arg1	polymorph					932:940	the most bioavailable polymorph	910:940	the most bioavailable polymorph	910:940	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	3	37	from	acyloxymethyl	433:445	arg1	attempt					506:512	attempt	506:512	attempt to improve these characteristics	506:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	3	38	theme	substituted	472:482	arg1	phosphonooxymethyl					484:501	substituted phosphonooxymethyl	472:501	substituted phosphonooxymethyl in attempt to improve these characteristics	472:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	0	39	theme	Aqueous	55:61	arg1	Solubility					63:72	Improved Aqueous Solubility	46:72	Improved Aqueous Solubility	46:72	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	2	40	theme	poor	300:303	arg1	solubility					305:314	its poor solubility	296:314	its poor solubility leading to poor bioavailability	296:346	The use of MBZ for cancer, however, is challenging due to its poor solubility leading to poor bioavailability.
29648826	2	41	theme	MBZ	249:251	arg1	use					242:244	The use	238:244	The use of MBZ for cancer	238:262	The use of MBZ for cancer, however, is challenging due to its poor solubility leading to poor bioavailability.
29648826	3	42	from	aminoacyloxymethyl	448:465	arg1	attempt					506:512	attempt	506:512	attempt to improve these characteristics	506:545	Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics.
29648826	4	43	theme	aqueous	681:687	arg1	solubility					689:698	aqueous solubility	681:698	aqueous solubility	681:698	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	5	44	theme	calculated	822:831	arg1	bioavailability					838:852	a calculated oral bioavailability	820:852	a calculated oral bioavailability of 52%	820:859	When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0- t and a 1.7-fold improvement in brain AUC0- t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph.
29648826	4	45	from	improvement	666:676	arg1	solubility					689:698	aqueous solubility	681:698	aqueous solubility	681:698	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	1	46	theme	anticancer	220:229	arg1	agent					231:235	an anticancer agent	217:235	an anticancer agent	217:235	Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent.
29648826	1	46	theme	anticancer	220:229	arg1	Mebendazole					117:127	Mebendazole (MBZ)	117:133	Mebendazole (MBZ)	117:133	Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent.
29648826	1	46	theme	anticancer	220:229	arg1	efficacy					205:212	efficacy	205:212	efficacy	205:212	Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent.
29648826	0	47	theme	Oral	78:81	arg1	Bioavailability					83:97	Oral Bioavailability	78:97	Oral Bioavailability	78:97	N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs.
29648826	7	48	theme	MBZ	1099:1101	arg1	prodrug					1088:1094	a prodrug	1086:1094	a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog	1086:1190	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	4	49	theme	oxy	599:601	arg1	isopropoxycarbonyl					580:597	isopropoxycarbonyl	580:597	isopropoxycarbonyl	580:597	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	49	theme	oxy	599:601	arg1	promoiety					633:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety	572:641	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	4	49	theme	oxy	599:601	arg1	phosphoryl					611:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	((isopropoxycarbonyl)oxy)methoxy)phosphoryl	578:620	Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility.
29648826	7	50	theme	better	1108:1113	arg1	properties					1131:1140	better physicochemical properties	1108:1140	better physicochemical properties	1108:1140	In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.
29648826	2	51	theme	poor	327:330	arg1	bioavailability					332:346	poor bioavailability	327:346	poor bioavailability	327:346	The use of MBZ for cancer, however, is challenging due to its poor solubility leading to poor bioavailability.
29317657	5	0	theme	potential	1001:1009	arg1	differences					1031:1041	potential biological reaction differences	1001:1041	potential biological reaction differences between responder and non-responder patients	1001:1086	Reactome data analysis further delineated potential biological reaction differences between responder and non-responder patients.
29317657	1	1	with	relationship	251:262	arg1	disorder					286:293	major depressive disorder	269:293	major depressive disorder (MDD)	269:299	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	1	1	with	relationship	251:262	arg1	response					330:337	antidepressant treatment response	305:337	antidepressant treatment response	305:337	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	1	1	with	relationship	251:262	arg1	MDD					296:298	MDD	296:298	MDD	296:298	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	5	2	theme	reaction	1022:1029	arg1	differences					1031:1041	potential biological reaction differences	1001:1041	potential biological reaction differences between responder and non-responder patients	1001:1086	Reactome data analysis further delineated potential biological reaction differences between responder and non-responder patients.
29317657	1	3	theme	depressive	275:284	arg1	disorder					286:293	major depressive disorder	269:293	major depressive disorder (MDD)	269:299	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	1	3	theme	depressive	275:284	arg1	MDD					296:298	MDD	296:298	MDD	296:298	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	2	4	theme	gender-dependent	493:508	arg1	correlations					510:521	gender-dependent correlations	493:521	gender-dependent correlations	493:521	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	2	5	theme	exploratory	373:383	arg1	study					385:389	our exploratory study	369:389	our exploratory study	369:389	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	0	6	theme	antidepressant	108:121	arg1	response					123:130	the antidepressant response	104:130	the antidepressant response	104:130	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	5	7	theme	biological	1011:1020	arg1	differences					1031:1041	potential biological reaction differences	1001:1041	potential biological reaction differences between responder and non-responder patients	1001:1086	Reactome data analysis further delineated potential biological reaction differences between responder and non-responder patients.
29317657	2	8	theme	symptoms	551:558	arg1	severity					528:535	severity	528:535	severity of depressive symptoms prior to initiating antidepressant treatment	528:603	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	6	9	theme	glycosylation	1135:1147	arg1	traits					1149:1154	specific glycosylation traits	1126:1154	specific glycosylation traits	1126:1154	Our preliminary results suggest that specific glycosylation traits are associated with depressive symptom severity and antidepressant response and may be of use as biomarkers.
29317657	2	10	theme	depressive	540:549	arg1	symptoms					551:558	depressive symptoms	540:558	depressive symptoms prior to initiating antidepressant treatment	540:603	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	4	11	theme	baseline	850:857	arg1	differences					901:911	baseline and post-antidepressant treatment pathway differences	850:911	differences	901:911	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	12	from	analysis	747:754	arg1	PBMCs					795:799	PBMCs	795:799	PBMCs	795:799	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	12	from	analysis	747:754	arg1	cells					788:792	peripheral blood mononuclear cells	759:792	peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20)	759:837	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	13	theme	proteomics	736:745	arg1	analysis					747:754	proteomics analysis	736:754	proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20)	736:837	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	14	theme	non-responder	935:947	arg1	patients					949:956	responder and non-responder patients	921:956	patients	949:956	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	0	15	theme	plasma/IgG	6:15	arg1	biosignatures					27:39	Blood plasma/IgG N-glycome biosignatures	0:39	Blood plasma/IgG N-glycome biosignatures	0:39	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	4	16	theme	MDD	817:819	arg1	patients					821:828	MDD patients	817:828	MDD patients (n = 20)	817:837	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	16	theme	MDD	817:819	arg1	n = 20					831:836	n = 20	831:836	n = 20	831:836	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	2	17	theme	N-glycan	404:411	arg1	profiles					413:420	N-glycan profiles	404:420	N-glycan profiles	404:420	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	0	18	theme	Blood	0:4	arg1	biosignatures					27:39	Blood plasma/IgG N-glycome biosignatures	0:39	Blood plasma/IgG N-glycome biosignatures	0:39	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	6	19	theme	specific	1126:1133	arg1	traits					1149:1154	specific glycosylation traits	1126:1154	specific glycosylation traits	1126:1154	Our preliminary results suggest that specific glycosylation traits are associated with depressive symptom severity and antidepressant response and may be of use as biomarkers.
29317657	1	20	theme	inflammatory	209:220	arg1	disorders					236:244	inflammatory and metabolic disorders	209:244	inflammatory and metabolic disorders	209:244	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	2	21	theme	MDD	461:463	arg1	patients					465:472	MDD patients	461:472	MDD patients (n = 18)	461:481	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	2	21	theme	MDD	461:463	arg1	n = 18					475:480	n = 18	475:480	n = 18	475:480	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	4	22	theme	pathway	893:899	arg1	differences					901:911	baseline and post-antidepressant treatment pathway differences	850:911	differences	901:911	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	23	theme	responder	921:929	arg1	patients					949:956	responder and non-responder patients	921:956	patients	949:956	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	6	24	theme	antidepressant	1208:1221	arg1	response					1223:1230	antidepressant response	1208:1230	antidepressant response	1208:1230	Our preliminary results suggest that specific glycosylation traits are associated with depressive symptom severity and antidepressant response and may be of use as biomarkers.
29317657	0	25	theme	N-glycome	17:25	arg1	biosignatures					27:39	Blood plasma/IgG N-glycome biosignatures	0:39	Blood plasma/IgG N-glycome biosignatures	0:39	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	1	26	theme	antidepressant	305:318	arg1	response					330:337	antidepressant treatment response	305:337	antidepressant treatment response	305:337	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	2	27	theme	antidepressant	580:593	arg1	treatment					595:603	antidepressant treatment	580:603	antidepressant treatment	580:603	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	0	28	dep	disorder	74:81	arg1	severity					91:98	symptom severity	83:98	symptom severity	83:98	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	1	29	theme	metabolic	226:234	arg1	disorders					236:244	inflammatory and metabolic disorders	209:244	inflammatory and metabolic disorders	209:244	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	1	30	theme	treatment	320:328	arg1	response					330:337	antidepressant treatment response	305:337	antidepressant treatment response	305:337	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	1	31	theme	disorders	236:244	arg1	context					198:204	the context	194:204	the context of inflammatory and metabolic disorders	194:244	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	2	32	theme	plasma	431:436	arg1	samples					438:444	blood plasma samples	425:444	blood plasma samples collected from MDD patients (n = 18)	425:481	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	5	33	theme	data	968:971	arg1	analysis					973:980	Reactome data analysis	959:980	Reactome data analysis	959:980	Reactome data analysis further delineated potential biological reaction differences between responder and non-responder patients.
29317657	6	34	theme	preliminary	1093:1103	arg1	results					1105:1111	Our preliminary results	1089:1111	Our preliminary results	1089:1111	Our preliminary results suggest that specific glycosylation traits are associated with depressive symptom severity and antidepressant response and may be of use as biomarkers.
29317657	1	35	gly	glycosylation	148:160	arg1	context					198:204	the context	194:204	the context of inflammatory and metabolic disorders	194:244	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	3	36	theme	antidepressant	701:714	arg1	response					716:723	clinical antidepressant response	692:723	clinical antidepressant response	692:723	In addition, several N-glycosylation traits showed gender-dependent associations with clinical antidepressant response.
29317657	5	37	theme	responder	1051:1059	arg1	patients					1079:1086	responder and non-responder patients	1051:1086	responder and non-responder patients	1051:1086	Reactome data analysis further delineated potential biological reaction differences between responder and non-responder patients.
29317657	2	38	theme	blood	425:429	arg1	samples					438:444	blood plasma samples	425:444	blood plasma samples collected from MDD patients (n = 18)	425:481	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	0	39	theme	depressive	63:72	arg1	disorder					74:81	major depressive disorder symptom severity and the antidepressant response	57:130	disorder	74:81	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	2	40	theme	prior	560:564	arg1	symptoms					551:558	depressive symptoms	540:558	depressive symptoms prior to initiating antidepressant treatment	540:603	In our exploratory study, we analysed N-glycan profiles in blood plasma samples collected from MDD patients (n = 18) and found gender-dependent correlations with severity of depressive symptoms prior to initiating antidepressant treatment.
29317657	3	41	theme	several	619:625	arg1	traits					643:648	several N-glycosylation traits	619:648	several N-glycosylation traits	619:648	In addition, several N-glycosylation traits showed gender-dependent associations with clinical antidepressant response.
29317657	0	42	theme	major	57:61	arg1	disorder					74:81	major depressive disorder symptom severity and the antidepressant response	57:130	disorder	74:81	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	3	43	theme	N-glycosylation	627:641	arg1	traits					643:648	several N-glycosylation traits	619:648	several N-glycosylation traits	619:648	In addition, several N-glycosylation traits showed gender-dependent associations with clinical antidepressant response.
29317657	1	44	theme	N-linked	139:146	arg1	glycosylation					148:160	N-linked glycosylation	139:160	N-linked glycosylation	139:160	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	4	45	theme	post-antidepressant	863:881	arg1	differences					901:911	baseline and post-antidepressant treatment pathway differences	850:911	differences	901:911	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	46	theme	mononuclear	776:786	arg1	PBMCs					795:799	PBMCs	795:799	PBMCs	795:799	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	46	theme	mononuclear	776:786	arg1	cells					788:792	peripheral blood mononuclear cells	759:792	peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20)	759:837	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	1	47	link	N-linked	139:146	arg1	glycosylation					148:160	N-linked glycosylation	139:160	N-linked glycosylation	139:160	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	3	48	theme	clinical	692:699	arg1	response					716:723	clinical antidepressant response	692:723	clinical antidepressant response	692:723	In addition, several N-glycosylation traits showed gender-dependent associations with clinical antidepressant response.
29317657	5	49	theme	non-responder	1065:1077	arg1	patients					1079:1086	responder and non-responder patients	1051:1086	responder and non-responder patients	1051:1086	Reactome data analysis further delineated potential biological reaction differences between responder and non-responder patients.
29317657	6	50	theme	symptom	1187:1193	arg1	severity					1195:1202	depressive symptom severity	1176:1202	depressive symptom severity	1176:1202	Our preliminary results suggest that specific glycosylation traits are associated with depressive symptom severity and antidepressant response and may be of use as biomarkers.
29317657	0	51	theme	symptom	83:89	arg1	severity					91:98	symptom severity	83:98	symptom severity	83:98	Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.
29317657	5	52	theme	Reactome	959:966	arg1	analysis					973:980	Reactome data analysis	959:980	Reactome data analysis	959:980	Reactome data analysis further delineated potential biological reaction differences between responder and non-responder patients.
29317657	3	53	theme	gender-dependent	657:672	arg1	associations					674:685	gender-dependent associations	657:685	gender-dependent associations with clinical antidepressant response	657:723	In addition, several N-glycosylation traits showed gender-dependent associations with clinical antidepressant response.
29317657	4	54	theme	blood	770:774	arg1	PBMCs					795:799	PBMCs	795:799	PBMCs	795:799	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	54	theme	blood	770:774	arg1	cells					788:792	peripheral blood mononuclear cells	759:792	peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20)	759:837	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	6	55	theme	depressive	1176:1185	arg1	severity					1195:1202	depressive symptom severity	1176:1202	depressive symptom severity	1176:1202	Our preliminary results suggest that specific glycosylation traits are associated with depressive symptom severity and antidepressant response and may be of use as biomarkers.
29317657	3	56	with	associations	674:685	arg1	response					716:723	clinical antidepressant response	692:723	clinical antidepressant response	692:723	In addition, several N-glycosylation traits showed gender-dependent associations with clinical antidepressant response.
29317657	4	57	theme	treatment	883:891	arg1	differences					901:911	baseline and post-antidepressant treatment pathway differences	850:911	differences	901:911	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	58	theme	peripheral	759:768	arg1	PBMCs					795:799	PBMCs	795:799	PBMCs	795:799	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	4	58	theme	peripheral	759:768	arg1	cells					788:792	peripheral blood mononuclear cells	759:792	peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20)	759:837	Follow up proteomics analysis in peripheral blood mononuclear cells (PBMCs) collected from MDD patients (n = 20) identified baseline and post-antidepressant treatment pathway differences between responder and non-responder patients.
29317657	1	59	theme	major	269:273	arg1	disorder					286:293	major depressive disorder	269:293	major depressive disorder (MDD)	269:299	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29317657	1	59	theme	major	269:273	arg1	MDD					296:298	MDD	296:298	MDD	296:298	While N-linked glycosylation has been extensively studied in the context of inflammatory and metabolic disorders, its relationship with major depressive disorder (MDD) and antidepressant treatment response has not been investigated.
29315539	4	0	theme	deprivation	543:553	arg1	influences					505:514	the influences	501:514	the influences of predation risk and food deprivation	501:553	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	12	1	theme	immediate	1902:1910	arg1	result					1912:1917	a direct and immediate result	1889:1917	a direct and immediate result of reduced food seeking	1889:1941	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	12	1	theme	immediate	1902:1910	arg1	retention					1876:1884	increased N retention	1864:1884	increased N retention	1864:1884	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	10	2	from	changes	1518:1524	arg1	guppies					1529:1535	guppies	1529:1535	guppies that increase N retention and decrease N excretion	1529:1586	These results suggest that predation risk, per se, triggers physiological changes in guppies that increase N retention and decrease N excretion.
29315539	5	3	theme	2 × 2	854:858	arg1	design					860:865	a 2 × 2 design	852:865	a 2 × 2 design	852:865	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	4	4	theme	predators	613:621	arg1	role					605:608	the role	601:608	the role of predators in nutrient cycles	601:640	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	2	5	theme	nitrogen	243:250	arg1	production					258:267	nitrogen waste production	243:267	nitrogen waste production	243:267	This stress accelerates prey's protein catabolism, nitrogen waste production, and nitrogen cycling.
29315539	5	6	theme	predation	813:821	arg1	risk					823:826	predation risk	813:826	predation risk	813:826	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	4	7	theme	nutrient	626:633	arg1	cycles					635:640	nutrient cycles	626:640	nutrient cycles	626:640	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	7	8	theme	guppy	1028:1032	arg1	response					1034:1041	guppy response	1028:1041	guppy response	1028:1041	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	4	9	from	role	605:608	arg1	cycles					635:640	nutrient cycles	626:640	nutrient cycles	626:640	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	12	10	theme	direct	1891:1896	arg1	result					1912:1917	a direct and immediate result	1889:1917	a direct and immediate result of reduced food seeking	1889:1941	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	12	10	theme	direct	1891:1896	arg1	retention					1876:1884	increased N retention	1864:1884	increased N retention	1864:1884	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	5	11	theme	separate	659:666	arg1	effects					681:687	the separate and combined effects	655:687	the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling	655:766	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	6	12	theme	chemical	902:909	arg1	cues					911:914	chemical cues	902:914	chemical cues from a natural predator of guppies	902:949	We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability.
29315539	8	13	theme	physiological	1187:1199	arg1	processes					1201:1209	N-linked physiological processes	1178:1209	N-linked physiological processes (N consumption, assimilation, excretion)	1178:1250	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	11	14	theme	food	1743:1746	arg1	restriction					1748:1758	predictable, predator-induced food restriction	1713:1758	predictable, predator-induced food restriction	1713:1758	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	0	15	theme	consumers	110:118	arg1	metabolism					96:105	the nitrogen metabolism	83:105	the nitrogen metabolism of consumers	83:118	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	5	16	from	effects	681:687	arg1	physiology					736:745	prey physiology	731:745	prey physiology	731:745	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	5	16	from	effects	681:687	arg1	cycling					760:766	nutrient cycling	751:766	nutrient cycling	751:766	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	12	17	theme	N	1874:1874	arg1	result					1912:1917	a direct and immediate result	1889:1917	a direct and immediate result of reduced food seeking	1889:1941	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	12	17	theme	N	1874:1874	arg1	retention					1876:1884	increased N retention	1864:1884	increased N retention	1864:1884	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	5	18	from	risk	823:826	arg1	design					860:865	a 2 × 2 design	852:865	a 2 × 2 design	852:865	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	9	19	theme	control	1424:1430	arg1	conditions					1432:1441	control conditions	1424:1441	control conditions	1424:1441	Guppies excreted substantially less under predation risk than they did under food deprivation or control conditions.
29315539	5	20	theme	food	711:714	arg1	deprivation					716:726	food deprivation	711:726	food deprivation	711:726	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	4	21	theme	prey	461:464	arg1	physiology					447:456	The physiology	443:456	The physiology of prey under predation risk	443:485	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	1	22	theme	nutrient	141:148	arg1	cycles					150:155	nutrient cycles	141:155	nutrient cycles	141:155	Predators can alter nutrient cycles simply by inducing stress in prey.
29315539	4	23	theme	predation	472:480	arg1	risk					482:485	predation risk	472:485	predation risk	472:485	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	7	24	dep	carbon	1102:1107	arg1	excretion					1136:1144	excretion	1136:1144	excretion	1136:1144	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	0	25	theme	deprivation	68:78	arg1	roles					35:39	the roles	31:39	the roles of predation risk and food deprivation in the nitrogen metabolism of consumers	31:118	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	6	26	theme	natural	923:929	arg1	predator					931:938	a natural predator	921:938	a natural predator of guppies	921:949	We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability.
29315539	0	27	from	roles	35:39	arg1	metabolism					96:105	the nitrogen metabolism	83:105	the nitrogen metabolism of consumers	83:118	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	6	28	from	predator	931:938	arg1	cues					911:914	chemical cues	902:914	chemical cues from a natural predator of guppies	902:949	We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability.
29315539	10	29	theme	N	1576:1576	arg1	excretion					1578:1586	N excretion	1576:1586	N excretion	1576:1586	These results suggest that predation risk, per se, triggers physiological changes in guppies that increase N retention and decrease N excretion.
29315539	5	30	theme	risk	702:705	arg1	effects					681:687	the separate and combined effects	655:687	the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling	655:766	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	5	31	theme	prey	731:734	arg1	physiology					736:745	prey physiology	731:745	prey physiology	731:745	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	8	32	theme	predation	1278:1286	arg1	risk					1288:1291	predation risk	1278:1291	predation risk	1278:1291	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	6	33	theme	food	997:1000	arg1	availability					1002:1013	food availability	997:1013	food availability	997:1013	We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability.
29315539	3	34	theme	nitrogen	425:432	arg1	cycling					434:440	nitrogen cycling	425:440	nitrogen cycling	425:440	Yet predators also reduce the feeding rates of their prey, inducing food deprivation that is expected to slow protein catabolism and nitrogen cycling.
29315539	7	35	theme	tissue	1095:1100	arg1	consumption					1051:1061	food consumption	1046:1061	food consumption	1046:1061	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	35	theme	tissue	1095:1100	arg1	carbon					1102:1107	tissue carbon	1095:1107	tissue carbon	1095:1107	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	4	36	theme	risk	529:532	arg1	influences					505:514	the influences	501:514	the influences of predation risk and food deprivation	501:553	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	12	37	theme	common	1790:1795	arg1	control					1806:1812	common hormonal control	1790:1812	common hormonal control	1790:1812	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	6	38	theme	food	967:970	arg1	deprivation					972:982	food deprivation	967:982	food deprivation	967:982	We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability.
29315539	3	39	theme	food	360:363	arg1	deprivation					365:375	food deprivation	360:375	food deprivation that is expected to slow protein catabolism and nitrogen cycling	360:440	Yet predators also reduce the feeding rates of their prey, inducing food deprivation that is expected to slow protein catabolism and nitrogen cycling.
29315539	0	40	theme	predation	44:52	arg1	risk					54:57	predation risk	44:57	predation risk	44:57	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	8	41	theme	consumption	1314:1324	arg1	independent					1294:1304	independent	1294:1304	independent	1294:1304	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	5	42	theme	nutrient	751:758	arg1	cycling					760:766	nutrient cycling	751:766	nutrient cycling	751:766	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	11	43	theme	predation	1631:1639	arg1	risk					1641:1644	predation risk	1631:1644	predation risk	1631:1644	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	13	44	theme	exposure	2104:2111	arg1	to predators					2113:2124	even short-term exposure to predators	2088:2124	even short-term exposure to predators	2088:2124	Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey.
29315539	12	45	theme	reduced	1922:1928	arg1	seeking					1935:1941	reduced food seeking	1922:1941	reduced food seeking	1922:1941	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	8	46	dep	processes	1201:1209	arg1	assimilation					1227:1238	assimilation	1227:1238	assimilation	1227:1238	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	8	46	dep	processes	1201:1209	arg1	consumption					1214:1224	N consumption	1212:1224	N consumption	1212:1224	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	8	46	dep	processes	1201:1209	arg1	excretion					1241:1249	excretion	1241:1249	excretion	1241:1249	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	5	47	theme	deprivation	716:726	arg1	effects					681:687	the separate and combined effects	655:687	the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling	655:766	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	12	48	theme	seeking	1935:1941	arg1	result					1912:1917	a direct and immediate result	1889:1917	a direct and immediate result of reduced food seeking	1889:1941	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	12	48	theme	seeking	1935:1941	arg1	retention					1876:1884	increased N retention	1864:1884	increased N retention	1864:1884	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	11	49	theme	slower	1605:1610	arg1	response					1661:1668	an adaptive response	1649:1668	an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction	1649:1758	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	11	49	theme	slower	1605:1610	arg1	metabolism					1614:1623	slower N metabolism	1605:1623	slower N metabolism under predation risk	1605:1644	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	4	50	theme	food	538:541	arg1	deprivation					543:553	food deprivation	538:553	food deprivation	538:553	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	7	51	theme	food	1046:1049	arg1	consumption					1051:1061	food consumption	1046:1061	food consumption	1046:1061	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	51	theme	food	1046:1049	arg1	nitrogen					1123:1130	nitrogen	1123:1130	nitrogen (N)	1123:1134	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	51	theme	food	1046:1049	arg1	assimilation					1150:1161	assimilation	1150:1161	assimilation	1150:1161	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	51	theme	food	1046:1049	arg1	growth					1064:1069	growth	1064:1069	growth	1064:1069	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	51	theme	food	1046:1049	arg1	carbon					1102:1107	tissue carbon	1095:1107	tissue carbon	1095:1107	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	51	theme	food	1046:1049	arg1	nitrogen					1109:1116	nitrogen	1109:1116	nitrogen	1109:1116	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	51	theme	food	1046:1049	arg1	density					1086:1092	tissue energy density	1072:1092	tissue energy density	1072:1092	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	2	52	theme	waste	252:256	arg1	production					258:267	nitrogen waste production	243:267	nitrogen waste production	243:267	This stress accelerates prey's protein catabolism, nitrogen waste production, and nitrogen cycling.
29315539	7	53	theme	tissue	1072:1077	arg1	consumption					1051:1061	food consumption	1046:1061	food consumption	1046:1061	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	53	theme	tissue	1072:1077	arg1	density					1086:1092	tissue energy density	1072:1092	tissue energy density	1072:1092	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	9	54	theme	predation	1369:1377	arg1	risk					1379:1382	predation risk	1369:1382	predation risk	1369:1382	Guppies excreted substantially less under predation risk than they did under food deprivation or control conditions.
29315539	10	55	theme	physiological	1504:1516	arg1	changes					1518:1524	physiological changes	1504:1524	physiological changes in guppies that increase N retention and decrease N excretion	1504:1586	These results suggest that predation risk, per se, triggers physiological changes in guppies that increase N retention and decrease N excretion.
29315539	11	56	theme	predictable	1713:1723	arg1	restriction					1748:1758	predictable, predator-induced food restriction	1713:1758	predictable, predator-induced food restriction	1713:1758	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	2	57	theme	nitrogen	274:281	arg1	cycling					283:289	nitrogen cycling	274:289	nitrogen cycling	274:289	This stress accelerates prey's protein catabolism, nitrogen waste production, and nitrogen cycling.
29315539	13	58	theme	cycling	2181:2187	arg1	speed					2170:2174	the speed	2166:2174	the speed of N cycling	2166:2187	Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey.
29315539	10	59	theme	N	1551:1551	arg1	retention					1553:1561	N retention	1551:1561	N retention	1551:1561	These results suggest that predation risk, per se, triggers physiological changes in guppies that increase N retention and decrease N excretion.
29315539	8	60	theme	N-linked	1178:1185	arg1	processes					1201:1209	N-linked physiological processes	1178:1209	N-linked physiological processes (N consumption, assimilation, excretion)	1178:1250	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	11	61	theme	restriction	1748:1758	arg1	face					1705:1708	the face	1701:1708	the face of predictable, predator-induced food restriction	1701:1758	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	9	62	theme	food	1404:1407	arg1	deprivation					1409:1419	food deprivation	1404:1419	food deprivation	1404:1419	Guppies excreted substantially less under predation risk than they did under food deprivation or control conditions.
29315539	12	63	theme	increased	1864:1872	arg1	result					1912:1917	a direct and immediate result	1889:1917	a direct and immediate result of reduced food seeking	1889:1941	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	12	63	theme	increased	1864:1872	arg1	retention					1876:1884	increased N retention	1864:1884	increased N retention	1864:1884	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	6	64	theme	predation	881:889	arg1	risk					891:894	predation risk	881:894	predation risk using chemical cues from a natural predator of guppies	881:949	We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability.
29315539	13	65	theme	N	2204:2204	arg1	turnover					2206:2213	N turnover	2204:2213	N turnover	2204:2213	Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey.
29315539	8	66	theme	N	1212:1212	arg1	assimilation					1227:1238	assimilation	1227:1238	assimilation	1227:1238	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	8	66	theme	N	1212:1212	arg1	consumption					1214:1224	N consumption	1212:1224	N consumption	1212:1224	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	8	66	theme	N	1212:1212	arg1	excretion					1241:1249	excretion	1241:1249	excretion	1241:1249	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	0	67	theme	risk	54:57	arg1	roles					35:39	the roles	31:39	the roles of predation risk and food deprivation in the nitrogen metabolism of consumers	31:118	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	13	68	theme	nutrient	2036:2043	arg1	cycling					2045:2051	nutrient cycling	2036:2051	nutrient cycling	2036:2051	Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey.
29315539	2	69	theme	protein	223:229	arg1	catabolism					231:240	prey's protein catabolism	216:240	prey's protein catabolism	216:240	This stress accelerates prey's protein catabolism, nitrogen waste production, and nitrogen cycling.
29315539	5	70	theme	food	832:835	arg1	deprivation					837:847	food deprivation	832:847	food deprivation	832:847	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	12	71	theme	predation	1949:1957	arg1	risk					1959:1962	predation risk	1949:1962	predation risk	1949:1962	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	11	72	theme	adaptive	1652:1659	arg1	response					1661:1668	an adaptive response	1649:1668	an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction	1649:1758	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	11	72	theme	adaptive	1652:1659	arg1	metabolism					1614:1623	slower N metabolism	1605:1623	slower N metabolism under predation risk	1605:1644	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	0	73	theme	food	63:66	arg1	deprivation					68:78	food deprivation	63:78	food deprivation	63:78	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	13	74	theme	predation-stress-based	1977:1998	arg1	hypotheses					2000:2009	predation-stress-based hypotheses	1977:2009	predation-stress-based hypotheses for how predators affect nutrient cycling by prey	1977:2059	Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey.
29315539	13	75	theme	N	2179:2179	arg1	cycling					2181:2187	N cycling	2179:2187	N cycling	2179:2187	Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey.
29315539	6	76	theme	guppies	943:949	arg1	predator					931:938	a natural predator	921:938	a natural predator of guppies	921:949	We simulated predation risk using chemical cues from a natural predator of guppies, and we created food deprivation by rationing food availability.
29315539	11	77	dep	predictable	1713:1723	arg1	predator-induced					1726:1741	predator-induced	1726:1741	predator-induced	1726:1741	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	11	78	theme	protein	1685:1691	arg1	loss					1693:1696	protein loss	1685:1696	protein loss	1685:1696	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	0	79	theme	nitrogen	87:94	arg1	metabolism					96:105	the nitrogen metabolism	83:105	the nitrogen metabolism of consumers	83:118	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	5	80	from	deprivation	837:847	arg1	design					860:865	a 2 × 2 design	852:865	a 2 × 2 design	852:865	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	3	81	theme	feeding	322:328	arg1	rates					330:334	the feeding rates	318:334	the feeding rates of their prey	318:348	Yet predators also reduce the feeding rates of their prey, inducing food deprivation that is expected to slow protein catabolism and nitrogen cycling.
29315539	3	82	theme	protein	402:408	arg1	catabolism					410:419	slow protein catabolism	397:419	slow protein catabolism	397:419	Yet predators also reduce the feeding rates of their prey, inducing food deprivation that is expected to slow protein catabolism and nitrogen cycling.
29315539	4	83	theme	predation	519:527	arg1	risk					529:532	predation risk	519:532	predation risk	519:532	The physiology of prey under predation risk thus balances the influences of predation risk and food deprivation, and this balance is central to understanding the role of predators in nutrient cycles.
29315539	3	84	theme	prey	345:348	arg1	rates					330:334	the feeding rates	318:334	the feeding rates of their prey	318:348	Yet predators also reduce the feeding rates of their prey, inducing food deprivation that is expected to slow protein catabolism and nitrogen cycling.
29315539	11	85	theme	N	1612:1612	arg1	response					1661:1668	an adaptive response	1649:1668	an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction	1649:1758	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	11	85	theme	N	1612:1612	arg1	metabolism					1614:1623	slower N metabolism	1605:1623	slower N metabolism under predation risk	1605:1644	We suggest that slower N metabolism under predation risk is an adaptive response that minimizes protein loss in the face of predictable, predator-induced food restriction.
29315539	7	86	theme	energy	1079:1084	arg1	consumption					1051:1061	food consumption	1046:1061	food consumption	1046:1061	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	7	86	theme	energy	1079:1084	arg1	density					1086:1092	tissue energy density	1072:1092	tissue energy density	1072:1092	We measured guppy response as food consumption, growth, tissue energy density, tissue carbon:nitrogen, and nitrogen (N) excretion and assimilation.
29315539	12	87	theme	hormonal	1797:1804	arg1	control					1806:1812	common hormonal control	1790:1812	common hormonal control	1790:1812	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	3	88	theme	slow	397:400	arg1	catabolism					410:419	slow protein catabolism	397:419	slow protein catabolism	397:419	Yet predators also reduce the feeding rates of their prey, inducing food deprivation that is expected to slow protein catabolism and nitrogen cycling.
29315539	5	89	theme	combined	672:679	arg1	effects					681:687	the separate and combined effects	655:687	the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling	655:766	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	8	90	theme	food	1309:1312	arg1	consumption					1314:1324	food consumption	1309:1324	food consumption	1309:1324	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	0	91	dep	Fasting	0:6	arg1	disentangling					17:29	disentangling	17:29	disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers	17:118	Fasting or fear: disentangling the roles of predation risk and food deprivation in the nitrogen metabolism of consumers.
29315539	12	92	theme	N	1770:1770	arg1	metabolism					1772:1781	N metabolism	1770:1781	N metabolism	1770:1781	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	8	93	link	N-linked	1178:1185	arg1	processes					1201:1209	N-linked physiological processes	1178:1209	N-linked physiological processes (N consumption, assimilation, excretion)	1178:1250	We found that N-linked physiological processes (N consumption, assimilation, excretion) were strongly affected by predation risk, independent of food consumption.
29315539	5	94	theme	predation	692:700	arg1	risk					702:705	predation risk	692:705	predation risk	692:705	We explored the separate and combined effects of predation risk and food deprivation on prey physiology and nutrient cycling by exposing guppies (Poecilia reticulata) to predation risk and food deprivation in a 2 × 2 design.
29315539	13	95	theme	short-term	2093:2102	arg1	to predators					2113:2124	even short-term exposure to predators	2088:2124	even short-term exposure to predators	2088:2124	Contrary to predation-stress-based hypotheses for how predators affect nutrient cycling by prey, our result indicates that even short-term exposure to predators may decelerate, rather than accelerate, the speed of N cycling by suppressing N turnover by prey.
29315539	12	96	theme	food	1930:1933	arg1	seeking					1935:1941	reduced food seeking	1922:1941	reduced food seeking	1922:1941	Notably, N metabolism shares common hormonal control with food seeking behavior, and we speculate that increased N retention is a direct and immediate result of reduced food seeking under predation risk.
29315539	10	97	theme	predation	1471:1479	arg1	risk					1481:1484	predation risk	1471:1484	predation risk	1471:1484	These results suggest that predation risk, per se, triggers physiological changes in guppies that increase N retention and decrease N excretion.
31622635	6	0	theme	infected	1176:1183	arg1	individuals					1200:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	8	1	theme	BSSL	1638:1641	arg1	gene					1643:1646	the BSSL gene	1634:1646	the BSSL gene	1634:1646	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	3	2	theme	HIV-1	482:486	arg1	progression					496:506	decreased HIV-1 disease progression	472:506	decreased HIV-1 disease progression	472:506	It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression.
31622635	2	3	theme	amino	284:288	arg1	repeats					295:301	O-linked glycosylated 11 amino acid repeats	259:301	O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	259:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	8	4	theme	BSSL	1530:1533	arg1	gene					1535:1538	the BSSL gene	1526:1538	the BSSL gene	1526:1538	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	5	5	theme	DC-SIGN	795:801	arg1	gene					803:806	the DC-SIGN gene	791:806	the DC-SIGN gene	791:806	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	6	6	theme	MSM	1072:1074	arg1	cohort					1076:1081	the HIV-1 infected MSM cohort	1053:1081	the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1053:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	6	theme	MSM	1072:1074	arg1	MOSAIC					1084:1089	MOSAIC	1084:1089	MOSAIC	1084:1089	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	2	7	theme	glycosylated	268:279	arg1	repeats					295:301	O-linked glycosylated 11 amino acid repeats	259:301	O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	259:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	4	8	theme	domains	634:640	arg1	number					617:622	individuals possessing one high (typically 14-21) and one low (typically 7-11) number	538:622	individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains	538:640	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	4	9	contain	possessing	550:559	arg1	individuals					538:548	individuals	538:548	individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains	538:640	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	4	9	contain	possessing	550:559	arg2	high					565:568	high	565:568	high	565:568	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	4	9	contain	possessing	550:559	arg2	low					596:598	low	596:598	low	596:598	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	6	10	theme	MEU	1137:1139	arg1	N = 30					1143:1148	HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1104:1210	N = 30	1143:1148	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	5	11	theme	BSSL	950:953	arg1	polymorphisms					955:967	BSSL polymorphisms	950:967	BSSL polymorphisms	950:967	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	8	12	theme	HCV	1568:1570	arg1	MEI					1581:1583	HCV infected MEI	1568:1583	HCV infected MEI	1568:1583	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	2	13	from	number	249:254	arg1	C-terminus					310:319	the C-terminus	306:319	the C-terminus of the protein, encoded in exon 11 of the gene	306:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	6	14	theme	uninfected	1125:1134	arg1	N = 30					1143:1148	HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1104:1210	N = 30	1143:1148	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	15	theme	MEI	1186:1188	arg1	individuals					1200:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	4	16	dep	high	565:568	arg1	14-21					581:585	14-21	581:585	14-21	581:585	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	5	17	theme	sexual	839:844	arg1	transmission					846:857	HCV sexual transmission	835:857	HCV sexual transmission	835:857	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	6	18	theme	multiple	1108:1115	arg1	N = 30					1143:1148	HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1104:1210	N = 30	1143:1148	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	8	19	from	number	1624:1629	arg1	gene					1643:1646	the BSSL gene	1634:1646	the BSSL gene	1634:1646	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	0	20	theme	HCV	64:66	arg1	susceptibility					68:81	HCV susceptibility	64:81	HCV susceptibility	64:81	Bile-salt stimulated lipase polymorphisms do not associate with HCV susceptibility.
31622635	4	21	theme	repeat	627:632	arg1	domains					634:640	repeat domains	627:640	repeat domains	627:640	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	6	22	theme	exposed	1164:1170	arg1	individuals					1200:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	4	23	theme	BSSL	685:688	arg1	binding					674:680	stronger binding	665:680	stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity	665:729	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	6	24	theme	cohort	1235:1240	arg1	ACS					1251:1253	ACS	1251:1253	ACS	1251:1253	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	24	theme	cohort	1235:1240	arg1	studies					1242:1248	the Amsterdam cohort studies	1221:1248	the Amsterdam cohort studies (ACS)	1221:1254	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	8	25	theme	exon	1604:1607	arg1	number					1624:1629	the exon 11 repeat copy number	1600:1629	the exon 11 repeat copy number in the BSSL gene	1600:1646	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	8	26	from	number	1476:1481	arg1	gene					1535:1538	the BSSL gene	1526:1538	the BSSL gene	1526:1538	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	8	27	theme	repeat	1612:1617	arg1	number					1624:1629	the exon 11 repeat copy number	1600:1629	the exon 11 repeat copy number in the BSSL gene	1600:1646	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	5	28	theme	diminished	886:895	arg1	expression					910:919	diminished DC-SIGN gene expression	886:919	diminished DC-SIGN gene expression	886:919	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	0	29	theme	Bile-salt	0:8	arg1	polymorphisms					28:40	Bile-salt stimulated lipase polymorphisms	0:40	Bile-salt stimulated lipase polymorphisms	0:40	Bile-salt stimulated lipase polymorphisms do not associate with HCV susceptibility.
31622635	3	30	theme	BSSL	400:403	arg1	genotypes					405:413	certain BSSL genotypes	392:413	certain BSSL genotypes	392:413	It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression.
31622635	0	31	theme	lipase	21:26	arg1	polymorphisms					28:40	Bile-salt stimulated lipase polymorphisms	0:40	Bile-salt stimulated lipase polymorphisms	0:40	Bile-salt stimulated lipase polymorphisms do not associate with HCV susceptibility.
31622635	6	32	from	cohort	1076:1081	arg1	ACS					1251:1253	ACS	1251:1253	ACS	1251:1253	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	32	from	cohort	1076:1081	arg1	drug					1268:1271	intravenous drug	1256:1271	intravenous drug	1256:1271	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	32	from	cohort	1076:1081	arg1	studies					1242:1248	the Amsterdam cohort studies	1221:1248	the Amsterdam cohort studies (ACS)	1221:1254	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	3	33	theme	decreased	430:438	arg1	transmission					446:457	decreased HIV-1 transmission	430:457	decreased HIV-1 transmission in vitro	430:466	It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression.
31622635	8	34	theme	copy	1471:1474	arg1	number					1476:1481	the copy number	1467:1481	the copy number of exon 11 repeats	1467:1500	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	2	35	theme	variant	241:247	arg1	number					249:254	a variant number	239:254	a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	239:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	5	36	theme	gene	905:908	arg1	expression					910:919	diminished DC-SIGN gene expression	886:919	diminished DC-SIGN gene expression	886:919	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	6	37	dep	N = 30	1143:1148	arg1	individuals					1200:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	2	38	gly	glycosylated	268:279	arg1	repeats					295:301	O-linked glycosylated 11 amino acid repeats	259:301	O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	259:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	8	39	theme	significant	1441:1451	arg1	difference					1453:1462	No statistical significant difference	1426:1462	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene	1426:1538	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	6	40	theme	HCV	1172:1174	arg1	individuals					1200:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	3	41	theme	disease	488:494	arg1	progression					496:506	decreased HIV-1 disease progression	472:506	decreased HIV-1 disease progression	472:506	It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression.
31622635	2	42	from	C-terminus	310:319	arg1	repeats					295:301	O-linked glycosylated 11 amino acid repeats	259:301	O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	259:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	2	42	from	C-terminus	310:319	arg1	number					249:254	a variant number	239:254	a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	239:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	4	43	theme	individuals	538:548	arg1	number					617:622	individuals possessing one high (typically 14-21) and one low (typically 7-11) number	538:622	individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains	538:640	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	3	44	theme	decreased	472:480	arg1	progression					496:506	decreased HIV-1 disease progression	472:506	decreased HIV-1 disease progression	472:506	It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression.
31622635	8	45	theme	HCV	1664:1666	arg1	susceptibility					1668:1681	HCV susceptibility	1664:1681	HCV susceptibility	1664:1681	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	2	46	theme	acid	290:293	arg1	repeats					295:301	O-linked glycosylated 11 amino acid repeats	259:301	O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	259:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	5	47	attach	linked	876:881	arg1	expression					910:919	diminished DC-SIGN gene expression	886:919	diminished DC-SIGN gene expression	886:919	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	5	47	attach	linked	876:881	arg2	which					863:867	which	863:867	which	863:867	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	6	48	theme	infected	1063:1070	arg1	cohort					1076:1081	the HIV-1 infected MSM cohort	1053:1081	the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1053:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	48	theme	infected	1063:1070	arg1	MOSAIC					1084:1089	MOSAIC	1084:1089	MOSAIC	1084:1089	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	4	49	contain	have	660:663	arg2	binding					674:680	stronger binding	665:680	stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity	665:729	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	4	49	contain	have	660:663	arg1	number					617:622	individuals possessing one high (typically 14-21) and one low (typically 7-11) number	538:622	individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains	538:640	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	1	50	gly	glycoprotein	123:134	arg1	lipase					104:109	Bile-salt stimulate lipase	84:109	Bile-salt stimulate lipase (BSSL)	84:116	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	1	50	gly	glycoprotein	123:134	arg1	glycoprotein					123:134	a glycoprotein	121:134	a glycoprotein found in human milk and blood that can potently bind DC-SIGN	121:195	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	5	51	theme	differential	998:1009	arg1	binding					1011:1017	differential binding	998:1017	differential binding to DC-SIGN	998:1028	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	2	52	with	polymorphic	222:232	arg1	number					249:254	a variant number	239:254	a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	239:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	6	53	theme	N = 32	1192:1197	arg1	individuals					1200:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	exposed HCV infected (MEI) (N = 32) individuals	1164:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	2	54	theme	BSSL	202:205	arg1	gene					207:210	The BSSL gene	198:210	The BSSL gene	198:210	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	2	54	theme	BSSL	202:205	arg1	polymorphic					222:232	polymorphic	222:232	polymorphic	222:232	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	7	55	from	numbers	1317:1323	arg1	exon					1339:1342	exon 11	1339:1345	exon 11	1339:1345	The numbers of repeats in exon 11 were determined by PCR with repeat distributions compared between MEI and MEU.
31622635	2	56	dep	glycosylated	268:279	arg1	O-linked					259:266	O-linked	259:266	O-linked	259:266	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	8	57	from	difference	1453:1462	arg1	combinations					1506:1517	combinations	1506:1517	combinations of, in the BSSL gene	1506:1538	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	8	57	from	difference	1453:1462	arg1	number					1476:1481	the copy number	1467:1481	the copy number of exon 11 repeats	1467:1500	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	5	58	theme	HCV	835:837	arg1	transmission					846:857	HCV sexual transmission	835:857	HCV sexual transmission	835:857	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	6	59	theme	exposed	1117:1123	arg1	N = 30					1143:1148	HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1104:1210	N = 30	1143:1148	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	60	theme	intravenous	1256:1266	arg1	drug					1268:1271	intravenous drug	1256:1271	intravenous drug	1256:1271	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	8	61	theme	infected	1572:1579	arg1	MEI					1581:1583	HCV infected MEI	1568:1583	HCV infected MEI	1568:1583	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	4	62	dep	DC-SIGN	693:699	arg1	activity					722:729	inhibitory activity	711:729	inhibitory activity	711:729	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	6	63	theme	HCV	1104:1106	arg1	N = 30					1143:1148	HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1104:1210	N = 30	1143:1148	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	1	64	theme	human	145:149	arg1	milk					151:154	human milk	145:154	human milk	145:154	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	7	65	theme	repeat	1375:1380	arg1	distributions					1382:1394	repeat distributions	1375:1394	repeat distributions	1375:1394	The numbers of repeats in exon 11 were determined by PCR with repeat distributions compared between MEI and MEU.
31622635	1	66	dep	lipase	104:109	arg1	stimulate					94:102	stimulate	94:102	stimulate	94:102	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	6	67	theme	Amsterdam	1225:1233	arg1	ACS					1251:1253	ACS	1251:1253	ACS	1251:1253	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	67	theme	Amsterdam	1225:1233	arg1	studies					1242:1248	the Amsterdam cohort studies	1221:1248	the Amsterdam cohort studies (ACS)	1221:1254	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	1	68	located	found	136:140	arg2	lipase					104:109	Bile-salt stimulate lipase	84:109	Bile-salt stimulate lipase (BSSL)	84:116	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	1	68	located	found	136:140	arg2	glycoprotein					123:134	a glycoprotein	121:134	a glycoprotein found in human milk and blood that can potently bind DC-SIGN	121:195	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	1	68	located	found	136:140	arg1	blood					160:164	blood	160:164	blood	160:164	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	1	68	located	found	136:140	arg1	milk					151:154	human milk	145:154	human milk	145:154	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	4	69	dep	number	617:622	arg1	7-11					611:614	7-11	611:614	typically 7-11	601:614	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	0	70	theme	stimulated	10:19	arg1	polymorphisms					28:40	Bile-salt stimulated lipase polymorphisms	0:40	Bile-salt stimulated lipase polymorphisms	0:40	Bile-salt stimulated lipase polymorphisms do not associate with HCV susceptibility.
31622635	5	71	theme	transmission	846:857	arg1	risk					827:830	risk	827:830	risk of HCV sexual transmission	827:857	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	8	72	theme	copy	1619:1622	arg1	number					1624:1629	the exon 11 repeat copy number	1600:1629	the exon 11 repeat copy number in the BSSL gene	1600:1646	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	4	73	theme	stronger	665:672	arg1	binding					674:680	stronger binding	665:680	stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity	665:729	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	2	74	theme	gene	363:366	arg1	exon					348:351	exon 11	348:354	exon 11 of the gene	348:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	6	75	theme	IDU	1280:1282	arg1	cohort					1285:1290	(IDU) cohort	1279:1290	(IDU) cohort (22 MEI and 40 MEU)	1279:1310	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	3	76	theme	certain	392:398	arg1	genotypes					405:413	certain BSSL genotypes	392:413	certain BSSL genotypes	392:413	It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression.
31622635	6	77	dep	cohort	1285:1290	arg1	MEI					1296:1298	22 MEI and 40 MEU	1293:1309	MEI	1296:1298	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	77	dep	cohort	1285:1290	arg1	MEU					1307:1309	22 MEI and 40 MEU	1293:1309	MEU	1307:1309	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	78	theme	HIV-1	1057:1061	arg1	cohort					1076:1081	the HIV-1 infected MSM cohort	1053:1081	the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals	1053:1210	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	6	78	theme	HIV-1	1057:1061	arg1	MOSAIC					1084:1089	MOSAIC	1084:1089	MOSAIC	1084:1089	DNA was isolated from the HIV-1 infected MSM cohort (MOSAIC) composed of HCV multiple exposed uninfected (MEU) (N = 30) and multiple exposed HCV infected (MEI) (N = 32) individuals and from the Amsterdam cohort studies (ACS) intravenous drug using (IDU) cohort (22 MEI and 40 MEU).
31622635	8	79	from	combinations	1506:1517	arg1	gene					1535:1538	the BSSL gene	1526:1538	the BSSL gene	1526:1538	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	3	80	theme	HIV-1	440:444	arg1	transmission					446:457	decreased HIV-1 transmission	430:457	decreased HIV-1 transmission in vitro	430:466	It has been shown that certain BSSL genotypes associate with decreased HIV-1 transmission in vitro and decreased HIV-1 disease progression.
31622635	5	81	theme	DC-SIGN	897:903	arg1	expression					910:919	diminished DC-SIGN gene expression	886:919	diminished DC-SIGN gene expression	886:919	Since we previously demonstrated that SNPs within the DC-SIGN gene can associate with risk of HCV sexual transmission and which can be linked to diminished DC-SIGN gene expression we aimed to identify whether BSSL polymorphisms associated similarly through differential binding to DC-SIGN.
31622635	1	82	theme	Bile-salt	84:92	arg1	lipase					104:109	Bile-salt stimulate lipase	84:109	Bile-salt stimulate lipase (BSSL)	84:116	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	1	82	theme	Bile-salt	84:92	arg1	glycoprotein					123:134	a glycoprotein	121:134	a glycoprotein found in human milk and blood that can potently bind DC-SIGN	121:195	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	1	82	theme	Bile-salt	84:92	arg1	BSSL					112:115	BSSL	112:115	BSSL	112:115	Bile-salt stimulate lipase (BSSL) is a glycoprotein found in human milk and blood that can potently bind DC-SIGN.
31622635	2	83	theme	repeats	295:301	arg1	number					249:254	a variant number	239:254	a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene	239:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	8	84	theme	exon	1486:1489	arg1	repeats					1494:1500	exon 11 repeats	1486:1500	exon 11 repeats	1486:1500	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	7	85	theme	repeats	1328:1334	arg1	numbers					1317:1323	The numbers	1313:1323	The numbers of repeats in exon 11	1313:1345	The numbers of repeats in exon 11 were determined by PCR with repeat distributions compared between MEI and MEU.
31622635	8	86	theme	statistical	1429:1439	arg1	difference					1453:1462	No statistical significant difference	1426:1462	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene	1426:1538	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	4	87	theme	inhibitory	711:720	arg1	activity					722:729	inhibitory activity	711:729	inhibitory activity	711:729	The protein forms dimers and individuals possessing one high (typically 14-21) and one low (typically 7-11) number of repeat domains has been shown to have stronger binding of BSSL to DC-SIGN and HIV-1 inhibitory activity in vitro.
31622635	2	88	theme	protein	328:334	arg1	C-terminus					310:319	the C-terminus	306:319	the C-terminus of the protein, encoded in exon 11 of the gene	306:366	The BSSL gene is highly polymorphic with a variant number of O-linked glycosylated 11 amino acid repeats at the C-terminus of the protein, encoded in exon 11 of the gene.
31622635	8	89	theme	repeats	1494:1500	arg1	combinations					1506:1517	combinations	1506:1517	combinations of, in the BSSL gene	1506:1538	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31622635	8	89	theme	repeats	1494:1500	arg1	number					1476:1481	the copy number	1467:1481	the copy number of exon 11 repeats	1467:1500	No statistical significant difference in the copy number of exon 11 repeats, or combinations of, in the BSSL gene was observed when comparing HCV infected MEI with MEU, thus the exon 11 repeat copy number in the BSSL gene does not affect HCV susceptibility.
31611643	4	0	dep	three-dimensional	526:542	arg1	3D					545:546	3D	545:546	3D	545:546	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	7	1	theme	viscous	1208:1214	arg1	solutions					1224:1232	Other viscous polymer solutions	1202:1232	Other viscous polymer solutions	1202:1232	Other viscous polymer solutions lack the same effect, indicating that the regulatory function of mucin does not result from its polymeric structure alone.
31611643	6	2	from	infection	1167:1175	arg1	model					1195:1199	a porcine burn model	1180:1199	a porcine burn model	1180:1199	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	9	3	theme	complex	1561:1567	arg1	structures					1569:1578	complex structures	1561:1578	complex structures	1561:1578	By isolating glycans from the mucin backbone, we assessed the collective activity of hundreds of complex structures in solution.
31611643	1	4	theme	human	137:141	arg1	body					143:146	the human body	133:146	the human body	133:146	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	4	5	theme	laboratory	549:558	arg1	model					560:564	a three-dimensional (3D) laboratory model	524:564	a three-dimensional (3D) laboratory model of native mucus	524:580	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	9	6	theme	structures	1569:1578	arg1	hundreds					1549:1556	hundreds	1549:1556	hundreds of complex structures	1549:1578	By isolating glycans from the mucin backbone, we assessed the collective activity of hundreds of complex structures in solution.
31611643	5	7	theme	3D	942:943	arg1	scaffold					945:952	the 3D scaffold	938:952	the 3D scaffold inside mucus	938:965	This phenotypic switch is triggered by mucins, which are polymers that are densely grafted with O-linked glycans that form the 3D scaffold inside mucus.
31611643	1	8	theme	mucus	96:100	arg1	gel					102:104	hydrated mucus gel	87:104	hydrated mucus gel	87:104	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	1	8	theme	mucus	96:100	arg1	slimy					80:84	A slimy	78:84	A slimy	78:84	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	4	9	theme	native	569:574	arg1	mucus					576:580	native mucus	569:580	native mucus	569:580	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	9	10	theme	hundreds	1549:1556	arg1	activity					1537:1544	the collective activity	1522:1544	the collective activity of hundreds of complex structures in solution	1522:1590	By isolating glycans from the mucin backbone, we assessed the collective activity of hundreds of complex structures in solution.
31611643	10	11	dep	Similar	1593:1599	arg1	free					1632:1635	free	1632:1635	free	1632:1635	Similar to their grafted counterparts, free mucin glycans potently regulate bacterial phenotypes even at relatively low concentrations.
31611643	1	12	from	epithelia	120:128	arg1	body					143:146	the human body	133:146	the human body	133:146	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	9	13	theme	mucin	1494:1498	arg1	backbone					1500:1507	the mucin backbone	1490:1507	the mucin backbone	1490:1507	By isolating glycans from the mucin backbone, we assessed the collective activity of hundreds of complex structures in solution.
31611643	5	14	theme	O-linked	911:918	arg1	glycans					920:926	O-linked glycans	911:926	O-linked glycans that form the 3D scaffold inside mucus	911:965	This phenotypic switch is triggered by mucins, which are polymers that are densely grafted with O-linked glycans that form the 3D scaffold inside mucus.
31611643	6	15	theme	various	1010:1016	arg1	scales					1018:1023	various scales	1010:1023	various scales	1010:1023	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	2	16	theme	first	236:240	arg1	line					242:245	the first line	232:245	the first line of defence	232:256	Mucus forms the first line of defence while housing trillions of microorganisms that constitute the microbiota1.
31611643	10	17	theme	grafted	1610:1616	arg1	counterparts					1618:1629	their grafted counterparts	1604:1629	their grafted counterparts	1604:1629	Similar to their grafted counterparts, free mucin glycans potently regulate bacterial phenotypes even at relatively low concentrations.
31611643	6	18	theme	virulence	1047:1055	arg1	pathways					1057:1064	distinct virulence pathways	1038:1064	distinct virulence pathways	1038:1064	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	10	19	theme	bacterial	1669:1677	arg1	phenotypes					1679:1688	bacterial phenotypes	1669:1688	bacterial phenotypes	1669:1688	Similar to their grafted counterparts, free mucin glycans potently regulate bacterial phenotypes even at relatively low concentrations.
31611643	12	20	theme	host	1874:1877	arg1	glycans					1855:1861	mucin glycans	1849:1861	mucin glycans	1849:1861	Thus, mucin glycans are potent host signals that 'tame' microorganisms, rendering them less harmful to the host.
31611643	12	20	theme	host	1874:1877	arg1	signals					1879:1885	potent host signals	1867:1885	potent host signals that 'tame' microorganisms, rendering them less harmful to the host	1867:1953	Thus, mucin glycans are potent host signals that 'tame' microorganisms, rendering them less harmful to the host.
31611643	7	21	theme	regulatory	1276:1285	arg1	function					1287:1294	the regulatory function	1272:1294	the regulatory function of mucin	1272:1303	Other viscous polymer solutions lack the same effect, indicating that the regulatory function of mucin does not result from its polymeric structure alone.
31611643	4	22	theme	mucus	576:580	arg1	model					560:564	a three-dimensional (3D) laboratory model	524:564	a three-dimensional (3D) laboratory model of native mucus	524:580	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	4	22	theme	mucus	576:580	arg1	bacterium					487:495	the bacterium	483:495	the bacterium Pseudomonas aeruginosa	483:518	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	6	23	theme	distinct	1038:1045	arg1	pathways					1057:1064	distinct virulence pathways	1038:1064	distinct virulence pathways	1038:1064	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	0	24	from	virulence	28:36	arg1	infection					67:75	infection	67:75	infection	67:75	Mucin glycans attenuate the virulence of Pseudomonas aeruginosa in infection.
31611643	9	25	theme	collective	1526:1535	arg1	activity					1537:1544	the collective activity	1522:1544	the collective activity of hundreds of complex structures in solution	1522:1590	By isolating glycans from the mucin backbone, we assessed the collective activity of hundreds of complex structures in solution.
31611643	7	26	theme	same	1243:1246	arg1	effect					1248:1253	the same effect	1239:1253	the same effect	1239:1253	Other viscous polymer solutions lack the same effect, indicating that the regulatory function of mucin does not result from its polymeric structure alone.
31611643	4	27	theme	virulence	647:655	arg1	genes					657:661	virulence genes	647:661	virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion	647:743	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	0	28	theme	Mucin	0:4	arg1	glycans					6:12	Mucin glycans	0:12	Mucin glycans	0:12	Mucin glycans attenuate the virulence of Pseudomonas aeruginosa in infection.
31611643	8	29	with	interactions	1374:1385	arg1	aeruginosa					1395:1404	P. aeruginosa	1392:1404	P. aeruginosa	1392:1404	We identify that interactions with P. aeruginosa are mediated by mucin-associated glycans (mucin glycans).
31611643	4	30	theme	siderophore	700:710	arg1	biosynthesis					712:723	siderophore biosynthesis	700:723	siderophore biosynthesis	700:723	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	4	31	theme	three-dimensional	526:542	arg1	model					560:564	a three-dimensional (3D) laboratory model	524:564	a three-dimensional (3D) laboratory model of native mucus	524:580	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	4	32	theme	toxin	729:733	arg1	secretion					735:743	toxin secretion	729:743	toxin secretion	729:743	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	6	33	from	cytotoxicity	1110:1121	arg1	vitro					1145:1149	vitro	1145:1149	vitro	1145:1149	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	5	34	theme	phenotypic	820:829	arg1	switch					831:836	This phenotypic switch	815:836	This phenotypic switch	815:836	This phenotypic switch is triggered by mucins, which are polymers that are densely grafted with O-linked glycans that form the 3D scaffold inside mucus.
31611643	6	35	theme	human	1126:1130	arg1	epithelia					1132:1140	human epithelia	1126:1140	human epithelia	1126:1140	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	11	36	theme	glycan	1777:1782	arg1	complexity					1784:1793	glycan complexity	1777:1793	glycan complexity	1777:1793	This regulatory function is likely dependent on glycan complexity, as monosaccharides do not attenuate virulence.
31611643	12	37	theme	mucin	1849:1853	arg1	glycans					1855:1861	mucin glycans	1849:1861	mucin glycans	1849:1861	Thus, mucin glycans are potent host signals that 'tame' microorganisms, rendering them less harmful to the host.
31611643	12	37	theme	mucin	1849:1853	arg1	signals					1879:1885	potent host signals	1867:1885	potent host signals that 'tame' microorganisms, rendering them less harmful to the host	1867:1953	Thus, mucin glycans are potent host signals that 'tame' microorganisms, rendering them less harmful to the host.
31611643	2	38	theme	defence	250:256	arg1	line					242:245	the first line	232:245	the first line of defence	232:256	Mucus forms the first line of defence while housing trillions of microorganisms that constitute the microbiota1.
31611643	3	39	theme	mucus	440:444	arg1	layer					446:450	the mucus layer	436:450	the mucus layer that regulate virulence	436:474	Rarely do these microorganisms cause infections in healthy mucus1, suggesting that mechanisms exist in the mucus layer that regulate virulence.
31611643	3	40	theme	healthy	384:390	arg1	mucus1					392:397	healthy mucus1	384:397	healthy mucus1	384:397	Rarely do these microorganisms cause infections in healthy mucus1, suggesting that mechanisms exist in the mucus layer that regulate virulence.
31611643	12	41	theme	potent	1867:1872	arg1	glycans					1855:1861	mucin glycans	1849:1861	mucin glycans	1849:1861	Thus, mucin glycans are potent host signals that 'tame' microorganisms, rendering them less harmful to the host.
31611643	12	41	theme	potent	1867:1872	arg1	signals					1879:1885	potent host signals	1867:1885	potent host signals that 'tame' microorganisms, rendering them less harmful to the host	1867:1953	Thus, mucin glycans are potent host signals that 'tame' microorganisms, rendering them less harmful to the host.
31611643	4	42	theme	infections	803:812	arg1	hallmark					783:790	biofilms-a hallmark	772:790	biofilms-a hallmark of mucosal infections	772:812	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	10	43	theme	mucin	1637:1641	arg1	glycans					1643:1649	Similar to their grafted counterparts, free mucin glycans	1593:1649	Similar to their grafted counterparts, free mucin glycans	1593:1649	Similar to their grafted counterparts, free mucin glycans potently regulate bacterial phenotypes even at relatively low concentrations.
31611643	7	44	theme	mucin	1299:1303	arg1	function					1287:1294	the regulatory function	1272:1294	the regulatory function of mucin	1272:1303	Other viscous polymer solutions lack the same effect, indicating that the regulatory function of mucin does not result from its polymeric structure alone.
31611643	4	45	dep	bacterium	487:495	arg1	aeruginosa					509:518	Pseudomonas aeruginosa	497:518	the bacterium Pseudomonas aeruginosa	483:518	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	10	46	theme	Similar	1593:1599	arg1	glycans					1643:1649	Similar to their grafted counterparts, free mucin glycans	1593:1649	Similar to their grafted counterparts, free mucin glycans	1593:1649	Similar to their grafted counterparts, free mucin glycans potently regulate bacterial phenotypes even at relatively low concentrations.
31611643	4	47	theme	mucosal	795:801	arg1	infections					803:812	mucosal infections	795:812	mucosal infections	795:812	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	7	48	theme	polymer	1216:1222	arg1	solutions					1224:1232	Other viscous polymer solutions	1202:1232	Other viscous polymer solutions	1202:1232	Other viscous polymer solutions lack the same effect, indicating that the regulatory function of mucin does not result from its polymeric structure alone.
31611643	0	49	theme	aeruginosa	53:62	arg1	virulence					28:36	the virulence	24:36	the virulence of Pseudomonas aeruginosa in infection	24:75	Mucin glycans attenuate the virulence of Pseudomonas aeruginosa in infection.
31611643	8	50	theme	mucin-associated	1422:1437	arg1	glycans					1439:1445	mucin-associated glycans	1422:1445	mucin-associated glycans (mucin glycans)	1422:1461	We identify that interactions with P. aeruginosa are mediated by mucin-associated glycans (mucin glycans).
31611643	8	50	theme	mucin-associated	1422:1437	arg1	glycans					1454:1460	mucin glycans	1448:1460	mucin glycans	1448:1460	We identify that interactions with P. aeruginosa are mediated by mucin-associated glycans (mucin glycans).
31611643	7	51	theme	polymeric	1330:1338	arg1	structure					1340:1348	its polymeric structure	1326:1348	its polymeric structure alone	1326:1354	Other viscous polymer solutions lack the same effect, indicating that the regulatory function of mucin does not result from its polymeric structure alone.
31611643	4	52	theme	quorum	684:689	arg1	sensing					691:697	quorum sensing	684:697	quorum sensing	684:697	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	10	53	theme	low	1709:1711	arg1	concentrations					1713:1726	relatively low concentrations	1698:1726	relatively low concentrations	1698:1726	Similar to their grafted counterparts, free mucin glycans potently regulate bacterial phenotypes even at relatively low concentrations.
31611643	5	54	link	O-linked	911:918	arg1	glycans					920:926	O-linked glycans	911:926	O-linked glycans that form the 3D scaffold inside mucus	911:965	This phenotypic switch is triggered by mucins, which are polymers that are densely grafted with O-linked glycans that form the 3D scaffold inside mucus.
31611643	8	55	theme	mucin	1448:1452	arg1	glycans					1439:1445	mucin-associated glycans	1422:1445	mucin-associated glycans (mucin glycans)	1422:1461	We identify that interactions with P. aeruginosa are mediated by mucin-associated glycans (mucin glycans).
31611643	8	55	theme	mucin	1448:1452	arg1	glycans					1454:1460	mucin glycans	1448:1460	mucin glycans	1448:1460	We identify that interactions with P. aeruginosa are mediated by mucin-associated glycans (mucin glycans).
31611643	6	56	theme	burn	1190:1193	arg1	model					1195:1199	a porcine burn model	1180:1199	a porcine burn model	1180:1199	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	6	57	theme	porcine	1182:1188	arg1	model					1195:1199	a porcine burn model	1180:1199	a porcine burn model	1180:1199	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	4	58	theme	biofilms-a	772:781	arg1	hallmark					783:790	biofilms-a hallmark	772:790	biofilms-a hallmark of mucosal infections	772:812	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	6	59	theme	isolated	987:994	arg1	mucins					996:1001	isolated mucins	987:1001	isolated mucins	987:1001	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	2	60	theme	microorganisms	285:298	arg1	trillions					272:280	trillions	272:280	trillions of microorganisms that constitute the microbiota1	272:330	Mucus forms the first line of defence while housing trillions of microorganisms that constitute the microbiota1.
31611643	1	61	theme	hydrated	87:94	arg1	gel					102:104	hydrated mucus gel	87:104	hydrated mucus gel	87:104	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	1	61	theme	hydrated	87:94	arg1	slimy					80:84	A slimy	78:84	A slimy	78:84	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	11	62	theme	regulatory	1734:1743	arg1	function					1745:1752	This regulatory function	1729:1752	This regulatory function	1729:1752	This regulatory function is likely dependent on glycan complexity, as monosaccharides do not attenuate virulence.
31611643	1	63	theme	wet	116:118	arg1	epithelia					120:128	all wet epithelia	112:128	all wet epithelia	112:128	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	1	64	theme	gastrointestinal	180:195	arg1	tracts					212:217	gastrointestinal and urogenital tracts	180:217	gastrointestinal and urogenital tracts	180:217	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
31611643	9	65	from	backbone	1500:1507	arg1	glycans					1477:1483	glycans	1477:1483	glycans from the mucin backbone	1477:1507	By isolating glycans from the mucin backbone, we assessed the collective activity of hundreds of complex structures in solution.
31611643	9	66	from	activity	1537:1544	arg1	solution					1583:1590	solution	1583:1590	solution	1583:1590	By isolating glycans from the mucin backbone, we assessed the collective activity of hundreds of complex structures in solution.
31611643	7	67	theme	Other	1202:1206	arg1	solutions					1224:1232	Other viscous polymer solutions	1202:1232	Other viscous polymer solutions	1202:1232	Other viscous polymer solutions lack the same effect, indicating that the regulatory function of mucin does not result from its polymeric structure alone.
31611643	6	68	theme	planktonic	1079:1088	arg1	lifestyle					1090:1098	a planktonic lifestyle	1077:1098	a planktonic lifestyle	1077:1098	Here, we show that isolated mucins act at various scales, suppressing distinct virulence pathways, promoting a planktonic lifestyle, reducing cytotoxicity to human epithelia in vitro and attenuating infection in a porcine burn model.
31611643	4	69	theme	genes	657:661	arg1	downregulation					629:642	downregulation	629:642	downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion	629:743	Using the bacterium Pseudomonas aeruginosa and a three-dimensional (3D) laboratory model of native mucus, we determined that exposure to mucus triggers downregulation of virulence genes that are involved in quorum sensing, siderophore biosynthesis and toxin secretion, and rapidly disintegrates biofilms-a hallmark of mucosal infections.
31611643	1	70	theme	urogenital	201:210	arg1	tracts					212:217	gastrointestinal and urogenital tracts	180:217	gastrointestinal and urogenital tracts	180:217	A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts.
30476078	6	0	from	surface	1363:1369	arg1	neo-expression					1307:1320	specific neo-expression	1298:1320	specific neo-expression of functional Lewisx antigen on the cell surface	1298:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	4	1	theme	FUT9	1054:1057	arg1	expression					1027:1036	expression	1027:1036	expression of the FUT4 and FUT9 enzymes	1027:1065	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	2	2	theme	colorectal	369:378	arg1	cells					387:391	colorectal cancer cells	369:391	colorectal cancer cells	369:391	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	7	3	theme	pronounced	1480:1489	arg1	differences					1491:1501	pronounced differences	1480:1501	pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes	1480:1584	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	9	4	theme	CRISPR-dCas9-VPR	1769:1784	arg1	system					1786:1791	the CRISPR-dCas9-VPR system	1765:1791	the CRISPR-dCas9-VPR system	1765:1791	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	4	5	dep	FUT4	1045:1048	arg1	the					1041:1043	the	1041:1043	the	1041:1043	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	4	5	dep	FUT4	1045:1048	arg1	enzymes					1059:1065	enzymes	1059:1065	enzymes	1059:1065	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	1	6	theme	tumor	290:294	arg1	progression					296:306	tumor progression	290:306	tumor progression	290:306	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	6	7	theme	Fut9	1238:1241	arg1	Induction					1212:1220	Induction	1212:1220	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR	1212:1284	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	9	8	from	possibilities	1915:1927	arg1	glycobiology					1932:1943	glycobiology	1932:1943	glycobiology	1932:1943	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	9	8	from	possibilities	1915:1927	arg1	research					1958:1965	oncology research	1949:1965	oncology research	1949:1965	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	6	9	theme	antigen	1343:1349	arg1	neo-expression					1307:1320	specific neo-expression	1298:1320	specific neo-expression of functional Lewisx antigen on the cell surface	1298:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	0	10	theme	cancer	150:155	arg1	cells					157:161	colorectal cancer cells	139:161	colorectal cancer cells	139:161	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	4	11	from	genes	949:953	arg1	line					1003:1006	the well-known murine colorectal cancer cell line	958:1006	the well-known murine colorectal cancer cell line	958:1006	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	4	11	from	genes	949:953	arg1	MC38					1009:1012	MC38	1009:1012	MC38	1009:1012	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	3	12	theme	experimental	611:622	arg1	models					624:629	experimental models	611:629	experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression	611:712	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	7	13	from	differences	1491:1501	arg1	properties					1523:1532	biosynthetic properties	1510:1532	biosynthetic properties	1510:1532	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	7	13	from	differences	1491:1501	arg1	stability					1553:1561	the expression stability	1538:1561	the expression stability	1538:1561	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	8	14	from	sialylation	1657:1667	arg1	MC38-glycovariants					1719:1736	the MC38-glycovariants	1715:1736	the MC38-glycovariants	1715:1736	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	1	15	gly	fucosylation	173:184	arg1	cells					196:200	cancer cells	189:200	cancer cells	189:200	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	3	16	theme	cancer-specific	649:663	arg1	regulation					665:674	cancer-specific regulation	649:674	cancer-specific regulation of fucosyltransferase gene expression	649:712	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	3	17	theme	cells	873:877	arg1	glycome					844:850	the glycome	840:850	the glycome of colorectal cancer cells	840:877	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	3	18	theme	Lewisx	820:825	arg1	synthesis					827:835	Lewisx synthesis	820:835	Lewisx synthesis	820:835	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	9	19	theme	gene	1876:1879	arg1	activation					1881:1890	transcriptional gene activation	1860:1890	transcriptional gene activation	1860:1890	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	1	20	theme	Aberrant	164:171	arg1	signature					221:229	a signature	219:229	a signature of malignant cell transformation	219:262	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	1	20	theme	Aberrant	164:171	arg1	fucosylation					173:184	Aberrant fucosylation	164:184	Aberrant fucosylation in cancer cells	164:200	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	7	21	from	glycans	1425:1431	arg1	cells					1465:1469	both MC38-FUT4 and MC38-FUT9 cells	1436:1469	both MC38-FUT4 and MC38-FUT9 cells	1436:1469	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	8	22	from	core-fucosylation	1638:1654	arg1	MC38-glycovariants					1719:1736	the MC38-glycovariants	1715:1736	the MC38-glycovariants	1715:1736	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	3	23	theme	colorectal	855:864	arg1	cells					873:877	colorectal cancer cells	855:877	colorectal cancer cells	855:877	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	0	24	theme	CRISPR-dCas9-VPR	71:86	arg1	technology					88:97	the CRISPR-dCas9-VPR technology	67:97	the CRISPR-dCas9-VPR technology	67:97	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	1	25	from	fucosylation	173:184	arg1	cells					196:200	cancer cells	189:200	cancer cells	189:200	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	4	26	theme	murine	973:978	arg1	line					1003:1006	the well-known murine colorectal cancer cell line	958:1006	the well-known murine colorectal cancer cell line	958:1006	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	4	26	theme	murine	973:978	arg1	MC38					1009:1012	MC38	1009:1012	MC38	1009:1012	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	2	27	gly	fucosylated	418:428	arg1	antigen					437:443	the fucosylated Lewisx antigen	414:443	the fucosylated Lewisx antigen	414:443	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	8	28	from	subtypes	1690:1697	arg1	MC38-glycovariants					1719:1736	the MC38-glycovariants	1715:1736	the MC38-glycovariants	1715:1736	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	7	29	theme	induced	1570:1576	arg1	enzymes					1578:1584	the induced enzymes	1566:1584	the induced enzymes	1566:1584	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	4	30	theme	cancer	991:996	arg1	line					1003:1006	the well-known murine colorectal cancer cell line	958:1006	the well-known murine colorectal cancer cell line	958:1006	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	4	30	theme	cancer	991:996	arg1	MC38					1009:1012	MC38	1009:1012	MC38	1009:1012	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	0	31	theme	N-glycome	114:122	arg1	alterations					124:134	potent N-glycome alterations	107:134	potent N-glycome alterations in colorectal cancer cells	107:161	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	9	32	theme	activation	1881:1890	arg1	method					1850:1855	a promising method	1838:1855	a promising method of transcriptional gene activation	1838:1890	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	2	33	theme	deregulated	467:477	arg1	expression					479:488	the deregulated expression	463:488	the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9)	463:587	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	5	34	dep	de	1151:1152	arg1	novo					1154:1157	novo	1154:1157	novo	1154:1157	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	0	35	theme	Transcriptional	0:14	arg1	activation					16:25	Transcriptional activation	0:25	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology	0:97	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	5	36	theme	expression	1164:1173	arg1	system					1204:1209	the CRISPR-dCas9-VPR system	1183:1209	namely the CRISPR-dCas9-VPR system	1176:1209	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	5	36	theme	expression	1164:1173	arg1	model					1142:1146	a physiologically relevant, guide RNA-based model	1098:1146	a physiologically relevant, guide RNA-based model of de novo gene expression	1098:1173	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	9	37	theme	transcriptional	1860:1874	arg1	activation					1881:1890	transcriptional gene activation	1860:1890	transcriptional gene activation	1860:1890	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	2	38	theme	fucosyltransferases	503:521	arg1	expression					479:488	the deregulated expression	463:488	the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9)	463:587	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	3	39	theme	gene	698:701	arg1	expression					703:712	fucosyltransferase gene expression	679:712	fucosyltransferase gene expression	679:712	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	2	40	theme	Lewisx	430:435	arg1	antigen					437:443	the fucosylated Lewisx antigen	414:443	the fucosylated Lewisx antigen	414:443	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	9	41	theme	broad	1897:1901	arg1	possibilities					1915:1927	broad application possibilities	1897:1927	broad application possibilities in glycobiology and oncology research	1897:1965	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	5	42	dep	relevant	1116:1123	arg1	RNA-based					1132:1140	RNA-based	1132:1140	RNA-based	1132:1140	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	2	43	theme	fucosyltransferase	529:546	arg1	FUT4					551:554	fucosyltransferase 4 (FUT4)	529:555	fucosyltransferase 4 (FUT4)	529:555	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	7	44	dep	cells	1465:1469	arg1	both					1436:1439	both	1436:1439	both	1436:1439	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	7	44	dep	cells	1465:1469	arg1	MC38-FUT9					1455:1463	MC38-FUT9	1455:1463	MC38-FUT9	1455:1463	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	8	45	theme	Lewisx	1597:1602	arg1	expression					1604:1613	Lewisx expression	1597:1613	Lewisx expression	1597:1613	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	1	46	theme	malignant	234:242	arg1	transformation					249:262	malignant cell transformation	234:262	malignant cell transformation	234:262	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	9	47	theme	promising	1840:1848	arg1	method					1850:1855	a promising method	1838:1855	a promising method of transcriptional gene activation	1838:1890	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	1	48	theme	transformation	249:262	arg1	fucosylation					173:184	Aberrant fucosylation	164:184	Aberrant fucosylation in cancer cells	164:200	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	1	48	theme	transformation	249:262	arg1	signature					221:229	a signature	219:229	a signature of malignant cell transformation	219:262	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	3	49	theme	synthesis	827:835	arg1	impact					810:815	the impact	806:815	the impact of Lewisx synthesis on the glycome of colorectal cancer cells	806:877	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	3	49	theme	synthesis	827:835	arg1	knowledge					739:747	our knowledge	735:747	our knowledge regarding the substrate specificity of these enzymes	735:800	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	9	50	theme	oncology	1949:1956	arg1	research					1958:1965	oncology research	1949:1965	oncology research	1949:1965	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	2	51	theme	cancer	380:385	arg1	cells					387:391	colorectal cancer cells	369:391	colorectal cancer cells	369:391	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	5	52	theme	CRISPR-dCas9-VPR	1187:1202	arg1	system					1204:1209	the CRISPR-dCas9-VPR system	1183:1209	namely the CRISPR-dCas9-VPR system	1176:1209	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	5	52	theme	CRISPR-dCas9-VPR	1187:1202	arg1	model					1142:1146	a physiologically relevant, guide RNA-based model	1098:1146	a physiologically relevant, guide RNA-based model of de novo gene expression	1098:1173	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	7	53	dep	properties	1523:1532	arg1	the					1506:1508	the	1506:1508	the	1506:1508	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	3	54	theme	substrate	763:771	arg1	specificity					773:783	the substrate specificity	759:783	the substrate specificity of these enzymes	759:800	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	6	55	theme	MC38	1252:1255	arg1	cells					1257:1261	MC38 cells	1252:1261	MC38 cells using CRISPR-dCas9-VPR	1252:1284	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	1	56	theme	cancer	189:194	arg1	cells					196:200	cancer cells	189:200	cancer cells	189:200	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	9	57	theme	application	1903:1913	arg1	possibilities					1915:1927	broad application possibilities	1897:1927	broad application possibilities in glycobiology and oncology research	1897:1965	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	9	58	from	method	1850:1855	arg1	conclusion					1742:1751	conclusion	1742:1751	conclusion	1742:1751	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	3	59	from	knowledge	739:747	arg1	glycome					844:850	the glycome	840:850	the glycome of colorectal cancer cells	840:877	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	9	60	theme	glycosyltransferase	1804:1822	arg1	expression					1824:1833	glycosyltransferase expression	1804:1833	glycosyltransferase expression	1804:1833	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	7	61	theme	N-linked	1416:1423	arg1	glycans					1425:1431	N-linked glycans	1416:1431	N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells	1416:1469	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	3	62	theme	enzymes	794:800	arg1	specificity					773:783	the substrate specificity	759:783	the substrate specificity of these enzymes	759:800	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	0	63	theme	colorectal	139:148	arg1	cells					157:161	colorectal cancer cells	139:161	colorectal cancer cells	139:161	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	9	64	with	method	1850:1855	arg1	possibilities					1915:1927	broad application possibilities	1897:1927	broad application possibilities in glycobiology and oncology research	1897:1965	In conclusion, exploiting the CRISPR-dCas9-VPR system to augment glycosyltransferase expression is a promising method of transcriptional gene activation with broad application possibilities in glycobiology and oncology research.
30476078	4	65	theme	Fut9	944:947	arg1	genes					949:953	the Fut4 and Fut9 genes	931:953	the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes	931:1065	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	6	66	theme	Lewisx	1336:1341	arg1	antigen					1343:1349	functional Lewisx antigen	1325:1349	functional Lewisx antigen on the cell surface	1325:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	2	67	theme	fucosyltransferase	561:578	arg1	FUT9					583:586	fucosyltransferase 9 (FUT9)	561:587	fucosyltransferase 9 (FUT9)	561:587	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	6	68	theme	Fut4	1229:1232	arg1	Induction					1212:1220	Induction	1212:1220	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR	1212:1284	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	5	69	theme	gene	1159:1162	arg1	expression					1164:1173	de novo gene expression	1151:1173	de novo gene expression	1151:1173	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	0	70	from	alterations	124:134	arg1	cells					157:161	colorectal cancer cells	139:161	colorectal cancer cells	139:161	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	3	71	from	impact	810:815	arg1	glycome					844:850	the glycome	840:850	the glycome of colorectal cancer cells	840:877	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	6	72	theme	specific	1298:1305	arg1	neo-expression					1307:1320	specific neo-expression	1298:1320	specific neo-expression of functional Lewisx antigen on the cell surface	1298:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	7	73	dep	both	1436:1439	arg1	MC38-FUT4					1441:1449	MC38-FUT4	1441:1449	MC38-FUT4	1441:1449	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	4	74	theme	Fut4	935:938	arg1	genes					949:953	the Fut4 and Fut9 genes	931:953	the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes	931:1065	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	3	75	theme	models	624:629	arg1	lack					603:606	the lack	599:606	the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression	599:712	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	4	76	theme	cell	998:1001	arg1	line					1003:1006	the well-known murine colorectal cancer cell line	958:1006	the well-known murine colorectal cancer cell line	958:1006	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	4	76	theme	cell	998:1001	arg1	MC38					1009:1012	MC38	1009:1012	MC38	1009:1012	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	5	77	used	utilized	1089:1096	arg2	we					1086:1087	we	1086:1087	we	1086:1087	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	7	78	theme	enzymes	1578:1584	arg1	properties					1523:1532	biosynthetic properties	1510:1532	biosynthetic properties	1510:1532	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	7	78	theme	enzymes	1578:1584	arg1	stability					1553:1561	the expression stability	1538:1561	the expression stability	1538:1561	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	7	79	link	N-linked	1416:1423	arg1	glycans					1425:1431	N-linked glycans	1416:1431	N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells	1416:1469	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	6	80	dep	Fut4	1229:1232	arg1	the					1225:1227	the	1225:1227	the	1225:1227	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	6	80	dep	Fut4	1229:1232	arg1	genes					1243:1247	genes	1243:1247	genes	1243:1247	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	6	81	from	Induction	1212:1220	arg1	cells					1257:1261	MC38 cells	1252:1261	MC38 cells using CRISPR-dCas9-VPR	1252:1284	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	3	82	theme	cancer	866:871	arg1	cells					873:877	colorectal cancer cells	855:877	colorectal cancer cells	855:877	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	0	83	theme	potent	107:112	arg1	alterations					124:134	potent N-glycome alterations	107:134	potent N-glycome alterations in colorectal cancer cells	107:161	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	4	84	theme	well-known	962:971	arg1	line					1003:1006	the well-known murine colorectal cancer cell line	958:1006	the well-known murine colorectal cancer cell line	958:1006	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	4	84	theme	well-known	962:971	arg1	MC38					1009:1012	MC38	1009:1012	MC38	1009:1012	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	6	85	theme	cell	1358:1361	arg1	surface					1363:1369	the cell surface	1354:1369	the cell surface	1354:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	4	86	theme	colorectal	980:989	arg1	line					1003:1006	the well-known murine colorectal cancer cell line	958:1006	the well-known murine colorectal cancer cell line	958:1006	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	4	86	theme	colorectal	980:989	arg1	MC38					1009:1012	MC38	1009:1012	MC38	1009:1012	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	8	87	from	antennarity	1670:1680	arg1	MC38-glycovariants					1719:1736	the MC38-glycovariants	1715:1736	the MC38-glycovariants	1715:1736	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	5	88	theme	relevant	1116:1123	arg1	system					1204:1209	the CRISPR-dCas9-VPR system	1183:1209	namely the CRISPR-dCas9-VPR system	1176:1209	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	5	88	theme	relevant	1116:1123	arg1	model					1142:1146	a physiologically relevant, guide RNA-based model	1098:1146	a physiologically relevant, guide RNA-based model of de novo gene expression	1098:1173	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	2	89	theme	increased	394:402	arg1	levels					404:409	increased levels	394:409	increased levels of the fucosylated Lewisx antigen	394:443	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	0	90	theme	fucosyltransferase	30:47	arg1	genes					55:59	fucosyltransferase (FUT) genes	30:59	fucosyltransferase (FUT) genes	30:59	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	4	91	theme	FUT4	1045:1048	arg1	expression					1027:1036	expression	1027:1036	expression of the FUT4 and FUT9 enzymes	1027:1065	Therefore, we sought to transcriptionally activate the Fut4 and Fut9 genes in the well-known murine colorectal cancer cell line, MC38, which lacks expression of the FUT4 and FUT9 enzymes.
30476078	3	92	theme	fucosyltransferase	679:696	arg1	expression					703:712	fucosyltransferase gene expression	679:712	fucosyltransferase gene expression	679:712	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	2	93	theme	antigen	437:443	arg1	levels					404:409	increased levels	394:409	increased levels of the fucosylated Lewisx antigen	394:443	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	0	94	theme	FUT	50:52	arg1	genes					55:59	fucosyltransferase (FUT) genes	30:59	fucosyltransferase (FUT) genes	30:59	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	6	95	from	antigen	1343:1349	arg1	surface					1363:1369	the cell surface	1354:1369	the cell surface	1354:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	2	96	theme	pertinent	493:501	arg1	fucosyltransferases					503:521	pertinent fucosyltransferases	493:521	pertinent fucosyltransferases	493:521	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	2	97	theme	fucosylated	418:428	arg1	antigen					437:443	the fucosylated Lewisx antigen	414:443	the fucosylated Lewisx antigen	414:443	Specifically, in colorectal cancer cells, increased levels of the fucosylated Lewisx antigen are attributed to the deregulated expression of pertinent fucosyltransferases, like fucosyltransferase 4 (FUT4) and fucosyltransferase 9 (FUT9).
30476078	0	98	theme	genes	55:59	arg1	activation					16:25	Transcriptional activation	0:25	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology	0:97	Transcriptional activation of fucosyltransferase (FUT) genes using the CRISPR-dCas9-VPR technology reveals potent N-glycome alterations in colorectal cancer cells.
30476078	5	99	theme	de	1151:1152	arg1	expression					1164:1173	de novo gene expression	1151:1173	de novo gene expression	1151:1173	For this purpose, we utilized a physiologically relevant, guide RNA-based model of de novo gene expression, namely the CRISPR-dCas9-VPR system.
30476078	7	100	theme	expression	1542:1551	arg1	stability					1553:1561	the expression stability	1538:1561	the expression stability	1538:1561	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	6	101	theme	functional	1325:1334	arg1	antigen					1343:1349	functional Lewisx antigen	1325:1349	functional Lewisx antigen on the cell surface	1325:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	6	102	from	neo-expression	1307:1320	arg1	surface					1363:1369	the cell surface	1354:1369	the cell surface	1354:1369	Induction of the Fut4 and Fut9 genes in MC38 cells using CRISPR-dCas9-VPR resulted in specific neo-expression of functional Lewisx antigen on the cell surface.
30476078	8	103	gly	core-fucosylation	1638:1654	arg1	N-glycans					1702:1710	N-glycans	1702:1710	N-glycans	1702:1710	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	8	103	gly	core-fucosylation	1638:1654	arg1	MC38-glycovariants					1719:1736	the MC38-glycovariants	1715:1736	the MC38-glycovariants	1715:1736	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	3	104	theme	expression	703:712	arg1	regulation					665:674	cancer-specific regulation	649:674	cancer-specific regulation of fucosyltransferase gene expression	649:712	However, the lack of experimental models closely mimicking cancer-specific regulation of fucosyltransferase gene expression has, so far, limited our knowledge regarding the substrate specificity of these enzymes and the impact of Lewisx synthesis on the glycome of colorectal cancer cells.
30476078	1	105	theme	cell	244:247	arg1	transformation					249:262	malignant cell transformation	234:262	malignant cell transformation	234:262	Aberrant fucosylation in cancer cells is considered as a signature of malignant cell transformation and it is associated with tumor progression, metastasis and resistance to chemotherapy.
30476078	7	106	theme	biosynthetic	1510:1521	arg1	properties					1523:1532	biosynthetic properties	1510:1532	biosynthetic properties	1510:1532	Interestingly, Lewisx was mainly carried by N-linked glycans in both MC38-FUT4 and MC38-FUT9 cells, despite pronounced differences in the biosynthetic properties and the expression stability of the induced enzymes.
30476078	8	107	gly	sialylation	1657:1667	arg1	N-glycans					1702:1710	N-glycans	1702:1710	N-glycans	1702:1710	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	8	107	gly	sialylation	1657:1667	arg1	MC38-glycovariants					1719:1736	the MC38-glycovariants	1715:1736	the MC38-glycovariants	1715:1736	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	8	108	theme	N-glycans	1702:1710	arg1	antennarity					1670:1680	antennarity	1670:1680	antennarity	1670:1680	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	8	108	theme	N-glycans	1702:1710	arg1	subtypes					1690:1697	the subtypes	1686:1697	the subtypes of N-glycans	1686:1710	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	8	108	theme	N-glycans	1702:1710	arg1	sialylation					1657:1667	sialylation	1657:1667	sialylation	1657:1667	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30476078	8	108	theme	N-glycans	1702:1710	arg1	core-fucosylation					1638:1654	core-fucosylation	1638:1654	core-fucosylation	1638:1654	Moreover, Lewisx expression was found to influence core-fucosylation, sialylation, antennarity and the subtypes of N-glycans in the MC38-glycovariants.
30275702	5	0	dep	lines	785:789	arg1	SK-MES-1					801:808	SK-MES-1	801:808	SK-MES-1	801:808	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	0	dep	lines	785:789	arg1	A549					792:795	A549	792:795	A549	792:795	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	0	dep	lines	785:789	arg1	lines					785:789	NSCLC cancer cell lines	767:789	NSCLC cancer cell lines (A549 and SK-MES-1)	767:809	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	1	1	theme	integrin	225:232	arg1	family					271:276	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	10	2	theme	lactate	1582:1588	arg1	LDHA					1607:1610	LDHA	1607:1610	LDHA	1607:1610	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	10	2	theme	lactate	1582:1588	arg1	A					1604:1604	lactate dehydrogenase A	1582:1604	lactate dehydrogenase A (LDHA)	1582:1611	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	1	3	theme	ligand	242:247	arg1	family					271:276	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	1	4	theme	N-linked	249:256	arg1	family					271:276	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	4	5	theme	significant	635:645	arg1	difference					647:656	significant difference	635:656	significant difference between advanced NSCLC and stage I/II NSCLC	635:700	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	5	6	theme	cancer	828:833	arg1	cells					835:839	cancer cells	828:839	cancer cells	828:839	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	8	7	theme	treatment	1182:1190	arg1	differentiation					1111:1125	cancer differentiation	1104:1125	cancer differentiation	1104:1125	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	8	7	theme	treatment	1182:1190	arg1	metastasis					1136:1145	distant metastasis	1128:1145	distant metastasis	1128:1145	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	8	7	theme	treatment	1182:1190	arg1	efficacy					1155:1162	the efficacy	1151:1162	the efficacy of platinum-based treatment	1151:1190	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	11	8	dep	CONCLUSION	1614:1623	arg1	suggest					1658:1664	suggest	1658:1664	suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients	1658:1748	CONCLUSION The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.
30275702	10	9	theme	A	1604:1604	arg1	downregulation					1564:1577	the downregulation	1560:1577	the downregulation of lactate dehydrogenase A (LDHA)	1560:1611	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	0	10	theme	poor	106:109	arg1	outcome					111:117	poor outcome	106:117	poor outcome of patients with advanced non-small-cell lung cancer	106:170	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	5	11	located	detected	816:823	arg1	cells					835:839	cancer cells	828:839	cancer cells	828:839	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	11	located	detected	816:823	arg2	ability					733:739	invasive ability	724:739	invasive ability	724:739	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	11	located	detected	816:823	arg2	resistance					712:721	The drug resistance	703:721	The drug resistance	703:721	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	11	located	detected	816:823	arg2	production					753:762	lactate production	745:762	lactate production	745:762	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	3	12	theme	OPN	518:520	arg1	levels					533:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors.
30275702	9	13	theme	OPN	1225:1227	arg1	factor					1262:1267	a potential factor	1250:1267	a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis	1250:1443	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	9	13	theme	OPN	1225:1227	arg1	levels					1240:1245	OPN expression levels	1225:1245	OPN expression levels	1225:1245	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	5	14	theme	lines	785:789	arg1	resistance					712:721	The drug resistance	703:721	The drug resistance	703:721	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	14	theme	lines	785:789	arg1	ability					733:739	invasive ability	724:739	invasive ability	724:739	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	14	theme	lines	785:789	arg1	production					753:762	lactate production	745:762	lactate production	745:762	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	1	15	gly	glycoprotein	258:269	arg1	glycoprotein					258:269	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	11	16	from	resistance	1727:1736	arg1	patients					1741:1748	patients	1741:1748	patients	1741:1748	CONCLUSION The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.
30275702	9	17	theme	platinum-based	1320:1333	arg1	chemotherapy					1335:1346	first-line platinum-based chemotherapy	1309:1346	first-line platinum-based chemotherapy using multivariate analysis	1309:1374	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	4	18	theme	stage	685:689	arg1	NSCLC					696:700	stage I/II NSCLC	685:700	stage I/II NSCLC	685:700	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	7	19	theme	NSCLC	999:1003	arg1	traits					1014:1019	NSCLC clinical traits	999:1019	NSCLC clinical traits	999:1019	Moreover, OPN correlates with NSCLC clinical traits.
30275702	5	20	theme	OPN	865:867	arg1	disturbance					850:860	the disturbance	846:860	the disturbance of OPN	846:867	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	0	21	theme	non-small-cell	145:158	arg1	cancer					165:170	advanced non-small-cell lung cancer	136:170	advanced non-small-cell lung cancer	136:170	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	2	22	theme	cell	471:474	arg1	cancer					481:486	non-small cell lung cancer	461:486	non-small cell lung cancer (NSCLC)	461:494	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	2	22	theme	cell	471:474	arg1	NSCLC					489:493	NSCLC	489:493	NSCLC	489:493	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	9	23	theme	distant	1426:1432	arg1	metastasis					1434:1443	cancer differentiation and distant metastasis	1399:1443	metastasis	1434:1443	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	1	24	theme	numerous	300:307	arg1	types					309:313	numerous types	300:313	numerous types of human malignancy	300:333	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	6	25	theme	cells	962:966	arg1	cytoplasm					943:951	the cytoplasm	939:951	the cytoplasm of NSCLC cells	939:966	RESULTS Immunostaining indicated that OPN was primarily expressed in the cytoplasm of NSCLC cells.
30275702	0	26	theme	lactate	64:70	arg1	production					72:81	lactate production	64:81	lactate production	64:81	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	1	27	theme	malignancy	324:333	arg1	types					309:313	numerous types	300:313	numerous types of human malignancy	300:333	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	10	28	theme	levels	1482:1487	arg1	abrogation					1464:1473	the abrogation	1460:1473	the abrogation of OPN levels	1460:1487	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	9	29	theme	cells	1300:1304	arg1	response					1288:1295	the response	1284:1295	the response of cells to first-line platinum-based chemotherapy using multivariate analysis	1284:1374	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	5	30	theme	cell	780:783	arg1	SK-MES-1					801:808	SK-MES-1	801:808	SK-MES-1	801:808	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	30	theme	cell	780:783	arg1	A549					792:795	A549	792:795	A549	792:795	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	30	theme	cell	780:783	arg1	lines					785:789	NSCLC cancer cell lines	767:789	NSCLC cancer cell lines (A549 and SK-MES-1)	767:809	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	9	31	theme	first-line	1309:1318	arg1	chemotherapy					1335:1346	first-line platinum-based chemotherapy	1309:1346	first-line platinum-based chemotherapy using multivariate analysis	1309:1374	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	2	32	theme	OPN	396:398	arg1	levels					386:391	the expression levels	371:391	the expression levels of OPN	371:398	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	0	33	theme	cancer	21:26	arg1	resistance					38:47	cancer cell drug resistance	21:47	cancer cell drug resistance	21:47	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	1	34	theme	family	271:276	arg1	Osteopontin					184:194	BACKGROUND Osteopontin	173:194	BACKGROUND Osteopontin (OPN)	173:200	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	1	34	theme	family	271:276	arg1	member					205:210	a member	203:210	a member of the small integrin binding ligand N-linked glycoprotein family	203:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	10	35	theme	lactate	1497:1503	arg1	production					1505:1514	lactate production	1497:1514	lactate production	1497:1514	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	3	36	from	immunohistochemistry	560:579	arg1	tumors					594:599	101 NSCLC tumors	584:599	101 NSCLC tumors	584:599	PATIENTS AND METHODS OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors.
30275702	0	37	theme	drug	33:36	arg1	resistance					38:47	cancer cell drug resistance	21:47	cancer cell drug resistance	21:47	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	9	38	theme	multivariate	1354:1365	arg1	analysis					1367:1374	multivariate analysis	1354:1374	multivariate analysis	1354:1374	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	2	39	theme	tumor	426:430	arg1	progression					432:442	tumor progression	426:442	tumor progression	426:442	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	5	40	theme	invasive	724:731	arg1	ability					733:739	invasive ability	724:739	invasive ability	724:739	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	41	theme	NSCLC	767:771	arg1	SK-MES-1					801:808	SK-MES-1	801:808	SK-MES-1	801:808	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	41	theme	NSCLC	767:771	arg1	A549					792:795	A549	792:795	A549	792:795	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	41	theme	NSCLC	767:771	arg1	lines					785:789	NSCLC cancer cell lines	767:789	NSCLC cancer cell lines (A549 and SK-MES-1)	767:809	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	8	42	theme	expression	1056:1065	arg1	levels					1067:1072	OPN expression levels	1052:1072	OPN expression levels	1052:1072	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	11	43	theme	cisplatin	1717:1725	arg1	resistance					1727:1736	cisplatin resistance	1717:1736	cisplatin resistance	1717:1736	CONCLUSION The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.
30275702	6	44	theme	RESULTS	870:876	arg1	Immunostaining					878:891	RESULTS Immunostaining	870:891	RESULTS Immunostaining	870:891	RESULTS Immunostaining indicated that OPN was primarily expressed in the cytoplasm of NSCLC cells.
30275702	11	45	theme	study	1652:1656	arg1	results					1629:1635	The results	1625:1635	The results of the current study	1625:1656	CONCLUSION The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.
30275702	1	46	theme	small	219:223	arg1	family					271:276	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	10	47	theme	dehydrogenase	1590:1602	arg1	LDHA					1607:1610	LDHA	1607:1610	LDHA	1607:1610	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	10	47	theme	dehydrogenase	1590:1602	arg1	A					1604:1604	lactate dehydrogenase A	1582:1604	lactate dehydrogenase A (LDHA)	1582:1611	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	11	48	from	prognosis	1703:1711	arg1	patients					1741:1748	patients	1741:1748	patients	1741:1748	CONCLUSION The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.
30275702	3	49	theme	PATIENTS	497:504	arg1	levels					533:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors.
30275702	1	50	theme	binding	234:240	arg1	family					271:276	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	8	51	theme	distant	1128:1134	arg1	metastasis					1136:1145	distant metastasis	1128:1145	distant metastasis	1128:1145	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	4	52	theme	protein	615:621	arg1	levels					623:628	The mRNA and protein levels	602:628	The mRNA and protein levels	602:628	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	3	53	theme	expression	522:531	arg1	levels					533:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors.
30275702	1	54	theme	BACKGROUND	173:182	arg1	OPN					197:199	OPN	197:199	OPN	197:199	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	1	54	theme	BACKGROUND	173:182	arg1	Osteopontin					184:194	BACKGROUND Osteopontin	173:194	BACKGROUND Osteopontin (OPN)	173:200	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	1	54	theme	BACKGROUND	173:182	arg1	member					205:210	a member	203:210	a member of the small integrin binding ligand N-linked glycoprotein family	203:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	3	55	theme	METHODS	510:516	arg1	levels					533:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels	497:538	PATIENTS AND METHODS OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors.
30275702	8	56	theme	platinum-based	1167:1180	arg1	treatment					1182:1190	platinum-based treatment	1167:1190	platinum-based treatment	1167:1190	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	7	57	theme	clinical	1005:1012	arg1	traits					1014:1019	NSCLC clinical traits	999:1019	NSCLC clinical traits	999:1019	Moreover, OPN correlates with NSCLC clinical traits.
30275702	4	58	theme	mRNA	606:609	arg1	levels					623:628	The mRNA and protein levels	602:628	The mRNA and protein levels	602:628	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	0	59	theme	advanced	136:143	arg1	cancer					165:170	advanced non-small-cell lung cancer	136:170	advanced non-small-cell lung cancer	136:170	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	9	60	theme	expression	1229:1238	arg1	factor					1262:1267	a potential factor	1250:1267	a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis	1250:1443	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	9	60	theme	expression	1229:1238	arg1	levels					1240:1245	OPN expression levels	1225:1245	OPN expression levels	1225:1245	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	0	61	with	patients	122:129	arg1	cancer					165:170	advanced non-small-cell lung cancer	136:170	advanced non-small-cell lung cancer	136:170	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	0	62	theme	lung	160:163	arg1	cancer					165:170	advanced non-small-cell lung cancer	136:170	advanced non-small-cell lung cancer	136:170	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	3	63	theme	NSCLC	588:592	arg1	tumors					594:599	101 NSCLC tumors	584:599	101 NSCLC tumors	584:599	PATIENTS AND METHODS OPN expression levels were detected using immunohistochemistry in 101 NSCLC tumors.
30275702	4	64	theme	I/II	691:694	arg1	NSCLC					696:700	stage I/II NSCLC	685:700	stage I/II NSCLC	685:700	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	9	65	theme	potential	1252:1260	arg1	factor					1262:1267	a potential factor	1250:1267	a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis	1250:1443	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	9	65	theme	potential	1252:1260	arg1	levels					1240:1245	OPN expression levels	1225:1245	OPN expression levels	1225:1245	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
30275702	2	66	theme	non-small	461:469	arg1	cancer					481:486	non-small cell lung cancer	461:486	non-small cell lung cancer (NSCLC)	461:494	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	2	66	theme	non-small	461:469	arg1	NSCLC					489:493	NSCLC	489:493	NSCLC	489:493	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	6	67	theme	NSCLC	956:960	arg1	cells					962:966	NSCLC cells	956:966	NSCLC cells	956:966	RESULTS Immunostaining indicated that OPN was primarily expressed in the cytoplasm of NSCLC cells.
30275702	2	68	from	role	418:421	arg1	patients					447:454	patients	447:454	patients with non-small cell lung cancer (NSCLC)	447:494	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	2	68	from	role	418:421	arg1	progression					432:442	tumor progression	426:442	tumor progression	426:442	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	4	69	theme	advanced	666:673	arg1	NSCLC					675:679	advanced NSCLC	666:679	advanced NSCLC	666:679	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	1	70	theme	human	318:322	arg1	malignancy					324:333	human malignancy	318:333	human malignancy	318:333	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	2	71	with	patients	447:454	arg1	cancer					481:486	non-small cell lung cancer	461:486	non-small cell lung cancer (NSCLC)	461:494	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	2	71	with	patients	447:454	arg1	NSCLC					489:493	NSCLC	489:493	NSCLC	489:493	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	5	72	theme	drug	707:710	arg1	resistance					712:721	The drug resistance	703:721	The drug resistance	703:721	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	2	73	theme	lung	476:479	arg1	cancer					481:486	non-small cell lung cancer	461:486	non-small cell lung cancer (NSCLC)	461:494	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	2	73	theme	lung	476:479	arg1	NSCLC					489:493	NSCLC	489:493	NSCLC	489:493	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	10	74	theme	OPN	1478:1480	arg1	levels					1482:1487	OPN levels	1478:1487	OPN levels	1478:1487	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	5	75	theme	cancer	773:778	arg1	SK-MES-1					801:808	SK-MES-1	801:808	SK-MES-1	801:808	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	75	theme	cancer	773:778	arg1	A549					792:795	A549	792:795	A549	792:795	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	5	75	theme	cancer	773:778	arg1	lines					785:789	NSCLC cancer cell lines	767:789	NSCLC cancer cell lines (A549 and SK-MES-1)	767:809	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	0	76	theme	patients	122:129	arg1	outcome					111:117	poor outcome	106:117	poor outcome of patients with advanced non-small-cell lung cancer	106:170	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	2	77	theme	present	348:354	arg1	study					356:360	The present study	344:360	The present study	344:360	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	0	78	theme	cell	28:31	arg1	resistance					38:47	cancer cell drug resistance	21:47	cancer cell drug resistance	21:47	Osteopontin promotes cancer cell drug resistance, invasion, and lactate production and is associated with poor outcome of patients with advanced non-small-cell lung cancer.
30275702	1	79	theme	glycoprotein	258:269	arg1	family					271:276	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	5	80	theme	lactate	745:751	arg1	production					753:762	lactate production	745:762	lactate production	745:762	The drug resistance, invasive ability and lactate production of NSCLC cancer cell lines (A549 and SK-MES-1) were detected in cancer cells with the disturbance of OPN.
30275702	8	81	theme	OPN	1052:1054	arg1	levels					1067:1072	OPN expression levels	1052:1072	OPN expression levels	1052:1072	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	2	82	theme	expression	375:384	arg1	levels					386:391	the expression levels	371:391	the expression levels of OPN	371:398	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	4	83	contain	have	630:633	arg1	levels					623:628	The mRNA and protein levels	602:628	The mRNA and protein levels	602:628	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	4	83	contain	have	630:633	arg2	difference					647:656	significant difference	635:656	significant difference between advanced NSCLC and stage I/II NSCLC	635:700	The mRNA and protein levels have significant difference between advanced NSCLC and stage I/II NSCLC.
30275702	10	84	theme	NSCLC	1519:1523	arg1	cells					1525:1529	NSCLC cells	1519:1529	NSCLC cells	1519:1529	Additionally, the abrogation of OPN levels reduced lactate production in NSCLC cells and occurred along side with the downregulation of lactate dehydrogenase A (LDHA).
30275702	11	85	theme	poor	1698:1701	arg1	prognosis					1703:1711	poor prognosis	1698:1711	poor prognosis	1698:1711	CONCLUSION The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.
30275702	8	86	theme	cancer	1104:1109	arg1	differentiation					1111:1125	cancer differentiation	1104:1125	cancer differentiation	1104:1125	The results demonstrated that OPN expression levels significantly correlated with cancer differentiation, distant metastasis and the efficacy of platinum-based treatment.
30275702	11	87	theme	current	1644:1650	arg1	study					1652:1656	the current study	1640:1656	the current study	1640:1656	CONCLUSION The results of the current study suggest that OPN may be able to predict poor prognosis and cisplatin resistance in patients.
30275702	2	88	dep	detected	362:369	arg1	PURPOSE					336:342	PURPOSE	336:342	PURPOSE	336:342	PURPOSE The present study detected the expression levels of OPN and evaluated its role in tumor progression in patients with non-small cell lung cancer (NSCLC).
30275702	1	89	link	N-linked	249:256	arg1	family					271:276	the small integrin binding ligand N-linked glycoprotein family	215:276	the small integrin binding ligand N-linked glycoprotein family	215:276	BACKGROUND Osteopontin (OPN), a member of the small integrin binding ligand N-linked glycoprotein family, has been analyzed in numerous types of human malignancy.
30275702	9	90	theme	cancer	1399:1404	arg1	differentiation					1406:1420	cancer differentiation and distant metastasis	1399:1443	differentiation	1406:1420	Notably, the results identified OPN expression levels as a potential factor for predicting the response of cells to first-line platinum-based chemotherapy using multivariate analysis, as well as predicting cancer differentiation and distant metastasis.
29920093	0	0	theme	Attachment	61:70	arg1	Temsavir					82:89	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	3	1	theme	preclinical	701:711	arg1	species					713:719	three preclinical species	695:719	three preclinical species	695:719	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	4	2	theme	solubility-limited	889:906	arg1	absorption					908:917	solubility-limited absorption	889:917	solubility-limited absorption	889:917	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	5	3	theme	treatment-experienced	1179:1199	arg1	patients					1216:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	4	4	theme	prodrug	988:994	arg1	preparation					950:960	the preparation	946:960	the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir)	946:1022	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	5	5	theme	4	1060:1060	arg1	formulation					1045:1055	An extended-release formulation	1025:1055	An extended-release formulation of 4	1025:1060	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	5	6	theme	HIV-1	1201:1205	arg1	patients					1216:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	0	7	theme	Temsavir	82:89	arg1	Fostemsavir					126:136	Its Phosphonooxymethyl Prodrug Fostemsavir	95:136	Its Phosphonooxymethyl Prodrug Fostemsavir	95:136	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	0	7	theme	Temsavir	82:89	arg1	Discovery					0:8	Discovery	0:8	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	0:89	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	4	8	from	properties	744:753	arg1	doses					794:798	higher doses	787:798	higher doses	787:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	5	9	from	part	1134:1137	arg1	patients					1216:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	2	10	link	N-linked	410:417	arg1	rings					446:450	N-linked, sp2-hybridized heteroaryl rings	410:450	N-linked, sp2-hybridized heteroaryl rings	410:450	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	3	11	theme	coplanarity	527:537	arg1	model					539:543	a coplanarity model	525:543	a coplanarity model	525:543	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	3	12	dep	adhered	514:520	arg1	Compounds					499:507	Compounds	499:507	Compounds that adhered to a coplanarity model	499:543	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	5	13	theme	infected	1207:1214	arg1	patients					1216:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	0	14	theme	Inhibitor	72:80	arg1	Temsavir					82:89	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	5	15	theme	clinical	1088:1095	arg1	trials					1097:1102	phase III clinical trials	1078:1102	phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients	1078:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	2	16	from	increases	322:330	arg1	potency					335:341	potency	335:341	potency	335:341	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	2	16	from	increases	322:330	arg1	properties					368:377	pharmacokinetic (PK) properties	347:377	pharmacokinetic (PK) properties	347:377	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	4	17	theme	physical	735:742	arg1	properties					744:753	the physical properties	731:753	the physical properties of 3 limited plasma exposure at higher doses	731:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	2	18	dep	pharmacokinetic	347:361	arg1	PK					364:365	PK	364:365	PK	364:365	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	1	19	theme	4-methoxy-6-azaindole	163:183	arg1	series					185:190	the 4-methoxy-6-azaindole series	159:190	the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1	159:250	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	2	20	dep	N-linked	410:417	arg1	sp2-hybridized					420:433	sp2-hybridized	420:433	sp2-hybridized	420:433	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	4	21	theme	plasma	768:773	arg1	exposure					775:782	3 limited plasma exposure	758:782	3 limited plasma exposure at higher doses	758:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	1	22	theme	series	185:190	arg1	optimization					143:154	The optimization	139:154	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529)	139:286	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	2	23	theme	heteroaryl	435:444	arg1	rings					446:450	N-linked, sp2-hybridized heteroaryl rings	410:450	N-linked, sp2-hybridized heteroaryl rings	410:450	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	4	24	theme	phosphonooxymethyl	969:986	arg1	prodrug					988:994	the phosphonooxymethyl prodrug 4	965:996	the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir)	965:1022	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	3	25	theme	antiviral	563:571	arg1	potency					573:579	targeted antiviral potency	554:579	targeted antiviral potency	554:579	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	4	26	theme	dissolution-	869:880	arg1	result					859:864	the result	855:864	the result of dissolution- and/or solubility-limited absorption	855:917	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	5	27	theme	combination	1149:1159	arg1	therapy					1161:1167	a drug combination therapy	1142:1167	a drug combination therapy in highly treatment-experienced HIV-1 infected patients	1142:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	4	28	theme	clinical	836:843	arg1	trials					845:850	clinical trials	836:850	clinical trials as the result of dissolution- and/or solubility-limited absorption	836:917	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	4	29	dep	prodrug	988:994	arg1	fostemsavir					1011:1021	fostemsavir	1011:1021	fostemsavir	1011:1021	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	4	29	dep	prodrug	988:994	arg1	BMS-663068					999:1008	BMS-663068	999:1008	BMS-663068	999:1008	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	5	30	from	patients	1216:1223	arg1	part					1134:1137	part	1134:1137	part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients	1134:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	1	31	theme	HIV-1	195:199	arg1	inhibitors					212:221	HIV-1 attachment inhibitors	195:221	HIV-1 attachment inhibitors (AIs) that originated with 1	195:250	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	1	31	theme	HIV-1	195:199	arg1	AIs					224:226	AIs	224:226	AIs	224:226	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	0	32	theme	Human	17:21	arg1	Type					46:49	the Human Immunodeficiency Virus Type 1	13:51	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	0	32	theme	Human	17:21	arg1	HIV-1					54:58	HIV-1	54:58	HIV-1	54:58	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	5	33	theme	therapy	1161:1167	arg1	part					1134:1137	part	1134:1137	part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients	1134:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	0	34	theme	Prodrug	118:124	arg1	Fostemsavir					126:136	Its Phosphonooxymethyl Prodrug Fostemsavir	95:136	Its Phosphonooxymethyl Prodrug Fostemsavir	95:136	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	4	35	theme	preclinical	809:819	arg1	studies					821:827	preclinical studies	809:827	preclinical studies	809:827	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	1	36	theme	attachment	201:210	arg1	inhibitors					212:221	HIV-1 attachment inhibitors	195:221	HIV-1 attachment inhibitors (AIs) that originated with 1	195:250	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	1	36	theme	attachment	201:210	arg1	AIs					224:226	AIs	224:226	AIs	224:226	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	2	37	theme	N-linked	410:417	arg1	rings					446:450	N-linked, sp2-hybridized heteroaryl rings	410:450	N-linked, sp2-hybridized heteroaryl rings	410:450	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	0	38	theme	Phosphonooxymethyl	99:116	arg1	Fostemsavir					126:136	Its Phosphonooxymethyl Prodrug Fostemsavir	95:136	Its Phosphonooxymethyl Prodrug Fostemsavir	95:136	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	3	39	theme	targeted	554:561	arg1	potency					573:579	targeted antiviral potency	554:579	targeted antiviral potency	554:579	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	1	40	theme	inhibitors	212:221	arg1	series					185:190	the 4-methoxy-6-azaindole series	159:190	the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1	159:250	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	0	41	theme	Virus	40:44	arg1	Type					46:49	the Human Immunodeficiency Virus Type 1	13:51	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	0	41	theme	Virus	40:44	arg1	HIV-1					54:58	HIV-1	54:58	HIV-1	54:58	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	0	42	theme	Immunodeficiency	23:38	arg1	Type					46:49	the Human Immunodeficiency Virus Type 1	13:51	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	0	42	theme	Immunodeficiency	23:38	arg1	HIV-1					54:58	HIV-1	54:58	HIV-1	54:58	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	5	43	theme	phase	1078:1082	arg1	trials					1097:1102	phase III clinical trials	1078:1102	phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients	1078:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	0	44	theme	Type	46:49	arg1	Temsavir					82:89	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir	13:89	Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.
29920093	5	45	from	therapy	1161:1167	arg1	patients					1216:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	highly treatment-experienced HIV-1 infected patients	1172:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	4	46	theme	a	920:920	arg1	deficiency					922:931	a deficiency	920:931	a deficiency	920:931	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	5	47	theme	extended-release	1028:1043	arg1	formulation					1045:1055	An extended-release formulation	1025:1055	An extended-release formulation of 4	1025:1060	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	3	48	theme	PK	678:679	arg1	properties					681:690	PK properties	678:690	PK properties	678:690	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	2	49	theme	beneficial	311:320	arg1	increases					322:330	The most beneficial increases	302:330	The most beneficial increases in potency and pharmacokinetic (PK) properties	302:377	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	5	50	theme	drug	1144:1147	arg1	therapy					1161:1167	a drug combination therapy	1142:1167	a drug combination therapy in highly treatment-experienced HIV-1 infected patients	1142:1223	An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
29920093	4	51	theme	absorption	908:917	arg1	result					859:864	the result	855:864	the result of dissolution- and/or solubility-limited absorption	855:917	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	1	52	dep	temsavir	263:270	arg1	BMS-626529					276:285	BMS-626529	276:285	BMS-626529	276:285	The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described.
29920093	3	53	theme	3	615:615	arg1	identification					597:610	the identification	593:610	the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species	593:719	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	4	54	theme	exposure	775:782	arg1	properties					744:753	the physical properties	731:753	the physical properties of 3 limited plasma exposure at higher doses	731:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	3	55	theme	targeted	656:663	arg1	exposure					665:672	targeted exposure	656:672	targeted exposure	656:672	Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species.
29920093	4	56	theme	limited	760:766	arg1	exposure					775:782	3 limited plasma exposure	758:782	3 limited plasma exposure at higher doses	758:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	4	57	theme	higher	787:792	arg1	doses					794:798	higher doses	787:798	higher doses	787:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	2	58	theme	nucleus	490:496	arg1	7-position					459:468	the 7-position	455:468	the 7-position of the heterocyclic nucleus	455:496	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	4	59	from	doses	794:798	arg1	properties					744:753	the physical properties	731:753	the physical properties of 3 limited plasma exposure at higher doses	731:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	4	59	from	doses	794:798	arg1	exposure					775:782	3 limited plasma exposure	758:782	3 limited plasma exposure at higher doses	758:798	However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir).
29920093	2	60	theme	pharmacokinetic	347:361	arg1	properties					368:377	pharmacokinetic (PK) properties	347:377	pharmacokinetic (PK) properties	347:377	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29920093	2	61	theme	heterocyclic	477:488	arg1	nucleus					490:496	the heterocyclic nucleus	473:496	the heterocyclic nucleus	473:496	The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus.
29673624	7	0	theme	Erlenmeyer	1283:1292	arg1	flasks					1294:1299	Erlenmeyer flasks	1283:1299	Erlenmeyer flasks	1283:1299	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	9	1	theme	Core	1452:1455	arg1	level					1464:1468	Core fucose level	1452:1468	Core fucose level of IgG1 #B in CHOK1SV	1452:1490	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	4	2	theme	Chinese	797:803	arg1	CHO					820:822	CHO	820:822	CHO	820:822	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	2	theme	Chinese	797:803	arg1	ovary					813:817	Chinese hamster ovary	797:817	two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively)	793:873	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	7	3	theme	mannose	1251:1257	arg1	level					1259:1263	high mannose level	1246:1263	high mannose level	1246:1263	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	8	4	theme	13	1447:1448	arg1	%					1442:1442	%	1442:1442	%	1442:1442	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	4	5	theme	IgG1	778:781	arg1	B					784:784	IgG1 #B	778:784	IgG1 #B	778:784	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	6	6	theme	core	1059:1062	arg1	fucose					1064:1069	core fucose	1059:1069	core fucose	1059:1069	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	11	7	theme	antibodies	1896:1905	arg1	levels					1881:1886	high mannose levels	1868:1886	high mannose levels of IgG1 antibodies	1868:1905	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	11	7	theme	antibodies	1896:1905	arg1	control					1836:1842	the control	1832:1842	the control of core fucosylated	1832:1862	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	6	8	theme	high	1125:1128	arg1	level					1138:1142	high mannose level	1125:1142	high mannose level	1125:1142	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	3	9	theme	mannosidase	522:532	arg1	Deoxymannojirimycin					474:492	Deoxymannojirimycin	474:492	Deoxymannojirimycin (DMJ)	474:498	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	3	9	theme	mannosidase	522:532	arg1	inhibitor					509:517	a known inhibitor	501:517	a known inhibitor of mannosidase	501:532	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	1	10	theme	Immunoglobulin	176:189	arg1	antibodies					211:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	7	11	theme	4	1270:1270	arg1	%					1271:1271	%	1271:1271	%	1271:1271	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	6	12	theme	glycoform	1045:1053	arg1	levels					1071:1076	N-linked complex glycoform and core fucose levels	1028:1076	N-linked complex glycoform and core fucose levels	1028:1076	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	9	13	theme	6	1601:1601	arg1	%					1602:1602	%	1602:1602	%	1602:1602	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	6	14	gly	glycoform	1045:1053	arg1	complex					1037:1043	complex glycoform	1037:1053	complex glycoform	1037:1053	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	10	15	theme	core	1628:1631	arg1	fucose					1633:1638	core fucose	1628:1638	core fucose	1628:1638	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	4	16	theme	cell	825:828	arg1	CHOK1SV					852:858	CHOK1SV	852:858	CHOK1SV	852:858	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	16	theme	cell	825:828	arg1	CHO-DXB-11					837:846	CHO-DXB-11	837:846	CHO-DXB-11	837:846	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	16	theme	cell	825:828	arg1	lines					830:834	two Chinese hamster ovary (CHO) cell lines	793:834	two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively)	793:873	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	6	17	theme	N-linked	1028:1035	arg1	levels					1071:1076	N-linked complex glycoform and core fucose levels	1028:1076	N-linked complex glycoform and core fucose levels	1028:1076	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	3	18	gly	glycosylation	574:586	arg1	antibodies					599:608	antibodies	599:608	antibodies	599:608	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	4	19	from	effect	615:620	arg1	levels					695:700	non-fucosylated glycoform levels	669:700	non-fucosylated glycoform levels	669:700	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	0	20	from	levels	60:65	arg1	production					92:101	glycosylated antibody production	70:101	glycosylated antibody production using deoxymannojirimycin	70:127	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	4	21	theme	DMJ	625:627	arg1	effect					615:620	The effect	611:620	The effect	611:620	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	10	22	theme	mannose	1649:1655	arg1	levels					1657:1662	high mannose levels	1644:1662	high mannose levels	1644:1662	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	4	23	gly	non-fucosylated	669:683	arg1	levels					695:700	non-fucosylated glycoform levels	669:700	non-fucosylated glycoform levels	669:700	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	5	24	theme	response	962:969	arg1	manner					971:976	a dose response manner	955:976	a dose response manner	955:976	DMJ affected glycan forms in a dose response manner.
29673624	3	25	theme	glycosylation	574:586	arg1	pattern					588:594	the glycosylation pattern	570:594	the glycosylation pattern of antibodies	570:608	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	1	26	theme	antibodies	211:220	arg1	region					154:159	the Fc region	147:159	the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies	147:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	4	27	theme	ovary	813:817	arg1	CHOK1SV					852:858	CHOK1SV	852:858	CHOK1SV	852:858	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	27	theme	ovary	813:817	arg1	CHO-DXB-11					837:846	CHO-DXB-11	837:846	CHO-DXB-11	837:846	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	27	theme	ovary	813:817	arg1	lines					830:834	two Chinese hamster ovary (CHO) cell lines	793:834	two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively)	793:873	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	28	theme	non-fucosylated	669:683	arg1	levels					695:700	non-fucosylated glycoform levels	669:700	non-fucosylated glycoform levels	669:700	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	9	29	theme	IgG1	1473:1476	arg1	B					1479:1479	IgG1 #B	1473:1479	IgG1 #B	1473:1479	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	7	30	theme	core	1184:1187	arg1	level					1196:1200	IgG1 #A core fucose level	1176:1200	IgG1 #A core fucose level in CHO-DXB-11	1176:1214	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	4	31	theme	μM	653:654	arg1	μM					662:663	5 μM - 500 μM	651:663	5 μM - 500 μM	651:663	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	0	32	theme	core	48:51	arg1	fucose					53:58	core fucose	48:58	core fucose	48:58	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	9	33	dep	%	1602:1602	arg1	to					1604:1605	to	1604:1605	to	1604:1605	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	1	34	theme	Fc	151:152	arg1	region					154:159	the Fc region	147:159	the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies	147:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	4	35	theme	Erlenmeyer	878:887	arg1	flasks					889:894	Erlenmeyer flasks	878:894	Erlenmeyer flasks	878:894	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	6	36	link	N-linked	1028:1035	arg1	levels					1071:1076	N-linked complex glycoform and core fucose levels	1028:1076	N-linked complex glycoform and core fucose levels	1028:1076	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	11	37	theme	high	1868:1871	arg1	levels					1881:1886	high mannose levels	1868:1886	high mannose levels of IgG1 antibodies	1868:1905	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	10	38	theme	viable	1687:1692	arg1	concentration					1699:1711	maximum viable cell concentration	1679:1711	maximum viable cell concentration	1679:1711	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	0	39	theme	glycosylated	70:81	arg1	production					92:101	glycosylated antibody production	70:101	glycosylated antibody production using deoxymannojirimycin	70:127	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	11	40	theme	fucosylated	1852:1862	arg1	levels					1881:1886	high mannose levels	1868:1886	high mannose levels of IgG1 antibodies	1868:1905	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	11	40	theme	fucosylated	1852:1862	arg1	control					1836:1842	the control	1832:1842	the control of core fucosylated	1832:1862	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	2	41	theme	glycosylation	389:401	arg1	profile					403:409	the glycosylation profile	385:409	the glycosylation profile	385:409	During the development of biosimilar therapeutics, adjustment of the glycosylation profile is required in order to match the reference innovator profile.
29673624	1	42	from	Glycosylation	130:142	arg1	region					154:159	the Fc region	147:159	the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies	147:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	7	43	from	level	1196:1200	arg1	CHO-DXB-11					1205:1214	CHO-DXB-11	1205:1214	CHO-DXB-11	1205:1214	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	7	44	theme	A	1182:1182	arg1	level					1196:1200	IgG1 #A core fucose level	1176:1200	IgG1 #A core fucose level in CHO-DXB-11	1176:1214	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	4	45	theme	bioreactors	913:923	arg1	processes					733:741	the biosynthesis processes	716:741	the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors	716:923	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	8	46	theme	scale	1322:1326	arg1	bioreactors					1328:1338	lab scale bioreactors	1318:1338	lab scale bioreactors	1318:1338	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	7	47	theme	IgG1	1176:1179	arg1	level					1196:1200	IgG1 #A core fucose level	1176:1200	IgG1 #A core fucose level in CHO-DXB-11	1176:1214	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	4	48	dep	μM	662:663	arg1	-					656:656	-	656:656	-	656:656	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	49	theme	IgG1	766:769	arg1	A					772:772	IgG1 #A	766:772	IgG1 #A	766:772	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	50	dep	IgG1	760:763	arg1	B					784:784	IgG1 #B	778:784	IgG1 #B	778:784	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	50	dep	IgG1	760:763	arg1	A					772:772	IgG1 #A	766:772	IgG1 #A	766:772	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	7	51	theme	10	1156:1157	arg1	μM					1159:1160	μM	1159:1160	μM	1159:1160	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	4	52	theme	lab	903:905	arg1	scale					907:911	lab scale	903:911	lab scale	903:911	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	8	53	theme	IgG1	1361:1364	arg1	level					1381:1385	IgG1 #A core fucose level	1361:1385	IgG1 #A core fucose level	1361:1385	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	11	54	theme	core	1847:1850	arg1	fucosylated					1852:1862	core fucosylated	1847:1862	core fucosylated	1847:1862	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	0	55	theme	mannose	36:42	arg1	levels					60:65	high mannose and core fucose levels	31:65	high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin	31:127	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	7	56	dep	%	1271:1271	arg1	to					1273:1274	to	1273:1274	to	1273:1274	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	8	57	theme	A	1367:1367	arg1	level					1381:1385	IgG1 #A core fucose level	1361:1385	IgG1 #A core fucose level	1361:1385	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	9	58	theme	fucose	1457:1462	arg1	level					1464:1468	Core fucose level	1452:1468	Core fucose level of IgG1 #B in CHOK1SV	1452:1490	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	9	59	theme	lab	1541:1543	arg1	bioreactors					1551:1561	lab scale bioreactors	1541:1561	lab scale bioreactors	1541:1561	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	8	60	theme	fucose	1374:1379	arg1	level					1381:1385	IgG1 #A core fucose level	1361:1385	IgG1 #A core fucose level	1361:1385	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	4	61	theme	IgG1	760:763	arg1	bioreactors					913:923	two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors	746:923	two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors	746:923	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	3	62	theme	known	503:507	arg1	Deoxymannojirimycin					474:492	Deoxymannojirimycin	474:492	Deoxymannojirimycin (DMJ)	474:498	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	3	62	theme	known	503:507	arg1	inhibitor					509:517	a known inhibitor	501:517	a known inhibitor of mannosidase	501:532	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	8	63	theme	high	1417:1420	arg1	level					1430:1434	high mannose level	1417:1434	high mannose level	1417:1434	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	1	64	theme	critical	227:234	arg1	Glycosylation					130:142	Glycosylation	130:142	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies	130:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	1	64	theme	critical	227:234	arg1	attribute					252:260	a critical protein quality attribute	225:260	a critical protein quality attribute which may affect the efficacy and safety of the molecule	225:317	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	2	65	theme	innovator	455:463	arg1	profile					465:471	the reference innovator profile	441:471	the reference innovator profile	441:471	During the development of biosimilar therapeutics, adjustment of the glycosylation profile is required in order to match the reference innovator profile.
29673624	9	66	theme	B	1479:1479	arg1	level					1464:1468	Core fucose level	1452:1468	Core fucose level of IgG1 #B in CHOK1SV	1452:1490	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	2	67	theme	biosimilar	346:355	arg1	therapeutics					357:368	biosimilar therapeutics	346:368	biosimilar therapeutics	346:368	During the development of biosimilar therapeutics, adjustment of the glycosylation profile is required in order to match the reference innovator profile.
29673624	1	68	theme	quality	244:250	arg1	Glycosylation					130:142	Glycosylation	130:142	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies	130:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	1	68	theme	quality	244:250	arg1	attribute					252:260	a critical protein quality attribute	225:260	a critical protein quality attribute which may affect the efficacy and safety of the molecule	225:317	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	7	69	theme	22	1276:1277	arg1	%					1271:1271	%	1271:1271	%	1271:1271	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	9	70	theme	high	1569:1572	arg1	mannose					1574:1580	high mannose	1569:1580	high mannose	1569:1580	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	8	71	theme	3	1441:1441	arg1	%					1442:1442	%	1442:1442	%	1442:1442	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	6	72	theme	fucose	1064:1069	arg1	levels					1071:1076	N-linked complex glycoform and core fucose levels	1028:1076	N-linked complex glycoform and core fucose levels	1028:1076	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	11	73	theme	IgG1	1891:1894	arg1	antibodies					1896:1905	IgG1 antibodies	1891:1905	IgG1 antibodies	1891:1905	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	8	74	theme	84	1399:1400	arg1	%					1394:1394	%	1394:1394	%	1394:1394	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	6	75	theme	mannose	1130:1136	arg1	level					1138:1142	high mannose level	1125:1142	high mannose level	1125:1142	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	4	76	from	concentrations	633:646	arg1	effect					615:620	The effect	611:620	The effect	611:620	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	1	77	theme	recombinant	164:174	arg1	antibodies					211:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	9	78	theme	μM	1531:1532	arg1	DMJ					1534:1536	10 μM DMJ	1528:1536	10 μM DMJ	1528:1536	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	9	79	theme	10	1528:1529	arg1	μM					1531:1532	μM	1531:1532	μM	1531:1532	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	7	80	theme	high	1246:1249	arg1	level					1259:1263	high mannose level	1246:1263	high mannose level	1246:1263	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	9	81	dep	%	1520:1520	arg1	to					1515:1516	to	1515:1516	to	1515:1516	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	1	82	theme	G	191:191	arg1	antibodies					211:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	4	83	theme	#	783:783	arg1	B					784:784	IgG1 #B	778:784	IgG1 #B	778:784	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	6	84	theme	complex	1037:1043	arg1	glycoform					1045:1053	complex glycoform	1037:1053	complex glycoform	1037:1053	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	11	85	theme	defined	1912:1918	arg1	range					1920:1924	a defined range	1910:1924	a defined range	1910:1924	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	1	86	theme	IgG	194:196	arg1	antibodies					211:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	9	87	theme	15	1607:1608	arg1	%					1602:1602	%	1602:1602	%	1602:1602	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	3	88	used	used	539:542	arg2	inhibitor					509:517	a known inhibitor	501:517	a known inhibitor of mannosidase	501:532	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	3	88	used	used	539:542	arg2	Deoxymannojirimycin					474:492	Deoxymannojirimycin	474:492	Deoxymannojirimycin (DMJ)	474:498	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	3	88	used	used	539:542	arg2	DMJ					495:497	DMJ	495:497	DMJ	495:497	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	5	89	theme	dose	957:960	arg1	manner					971:976	a dose response manner	955:976	a dose response manner	955:976	DMJ affected glycan forms in a dose response manner.
29673624	1	90	theme	therapeutic	199:209	arg1	antibodies					211:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	recombinant Immunoglobulin G (IgG) therapeutic antibodies	164:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	7	91	from	%	1278:1278	arg1	flasks					1294:1299	Erlenmeyer flasks	1283:1299	Erlenmeyer flasks	1283:1299	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	7	92	theme	%	1223:1223	arg1	%					1230:1230	92% to 73%	1221:1230	92% to 73%	1221:1230	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	8	93	dep	%	1442:1442	arg1	to					1444:1445	to	1444:1445	to	1444:1445	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	10	94	theme	high	1644:1647	arg1	levels					1657:1662	high mannose levels	1644:1662	high mannose levels	1644:1662	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	4	95	theme	hamster	805:811	arg1	CHO					820:822	CHO	820:822	CHO	820:822	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	95	theme	hamster	805:811	arg1	ovary					813:817	Chinese hamster ovary	797:817	two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively)	793:873	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	96	theme	μM	662:663	arg1	concentrations					633:646	concentrations	633:646	concentrations of 5 μM - 500 μM	633:663	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	5	97	theme	glycan	939:944	arg1	forms					946:950	glycan forms	939:950	glycan forms	939:950	DMJ affected glycan forms in a dose response manner.
29673624	3	98	theme	antibodies	599:608	arg1	pattern					588:594	the glycosylation pattern	570:594	the glycosylation pattern of antibodies	570:608	Deoxymannojirimycin (DMJ), a known inhibitor of mannosidase, was used in this study to modulate the glycosylation pattern of antibodies.
29673624	9	99	from	level	1464:1468	arg1	CHOK1SV					1484:1490	CHOK1SV	1484:1490	CHOK1SV	1484:1490	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	0	100	theme	fucose	53:58	arg1	levels					60:65	high mannose and core fucose levels	31:65	high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin	31:127	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	9	101	theme	#	1478:1478	arg1	B					1479:1479	IgG1 #B	1473:1479	IgG1 #B	1473:1479	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	1	102	dep	efficacy	283:290	arg1	the					279:281	the	279:281	the	279:281	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	7	103	theme	fucose	1189:1194	arg1	level					1196:1200	IgG1 #A core fucose level	1176:1200	IgG1 #A core fucose level in CHO-DXB-11	1176:1214	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	4	104	dep	lines	830:834	arg1	CHOK1SV					852:858	CHOK1SV	852:858	CHOK1SV	852:858	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	104	dep	lines	830:834	arg1	CHO-DXB-11					837:846	CHO-DXB-11	837:846	CHO-DXB-11	837:846	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	4	104	dep	lines	830:834	arg1	lines					830:834	two Chinese hamster ovary (CHO) cell lines	793:834	two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively)	793:873	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	7	105	dep	%	1230:1230	arg1	to					1225:1226	to	1225:1226	to	1225:1226	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	10	106	theme	cell	1694:1697	arg1	concentration					1699:1711	maximum viable cell concentration	1679:1711	maximum viable cell concentration	1679:1711	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	0	107	theme	antibody	83:90	arg1	production					92:101	glycosylated antibody production	70:101	glycosylated antibody production using deoxymannojirimycin	70:127	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	8	108	dep	%	1394:1394	arg1	to					1396:1397	to	1396:1397	to	1396:1397	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	11	109	theme	mannose	1873:1879	arg1	levels					1881:1886	high mannose levels	1868:1886	high mannose levels of IgG1 antibodies	1868:1905	This study demonstrated that DMJ can enable the control of core fucosylated and high mannose levels of IgG1 antibodies in a defined range.
29673624	8	110	theme	lab	1318:1320	arg1	bioreactors					1328:1338	lab scale bioreactors	1318:1338	lab scale bioreactors	1318:1338	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	10	111	theme	cell	1753:1756	arg1	%					1784:1784	less than 10%	1772:1784	less than 10%	1772:1784	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	10	111	theme	cell	1753:1756	arg1	productivity					1758:1769	cell productivity	1753:1769	cell productivity (less than 10%)	1753:1785	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	10	112	theme	maximum	1679:1685	arg1	concentration					1699:1711	maximum viable cell concentration	1679:1711	maximum viable cell concentration	1679:1711	While affecting core fucose and high mannose levels, DMJ decreased maximum viable cell concentration by 16% and did not significantly affect cell productivity (less than 10%).
29673624	7	113	theme	#	1181:1181	arg1	level					1196:1200	IgG1 #A core fucose level	1176:1200	IgG1 #A core fucose level in CHO-DXB-11	1176:1214	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	4	114	theme	biosynthesis	720:731	arg1	processes					733:741	the biosynthesis processes	716:741	the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors	716:923	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	0	115	theme	efficient	3:11	arg1	method					13:18	An efficient method	0:18	An efficient method	0:18	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	0	116	gly	glycosylated	70:81	arg1	production					92:101	glycosylated antibody production	70:101	glycosylated antibody production using deoxymannojirimycin	70:127	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	9	117	theme	%	1513:1513	arg1	%					1520:1520	81% to 73%	1511:1520	81% to 73% using 10 μM DMJ	1511:1536	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	8	118	theme	15 μM	1341:1345	arg1	DMJ					1347:1349	15 μM DMJ	1341:1349	15 μM DMJ	1341:1349	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	4	119	theme	glycoform	685:693	arg1	levels					695:700	non-fucosylated glycoform levels	669:700	non-fucosylated glycoform levels	669:700	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	7	120	theme	μM	1159:1160	arg1	DMJ					1162:1164	10 μM DMJ	1156:1164	10 μM DMJ	1156:1164	10 μM DMJ decreased IgG1 #A core fucose level in CHO-DXB-11 from 92% to 73% and increased high mannose level from 4% to 22% in Erlenmeyer flasks.
29673624	0	121	theme	high	31:34	arg1	mannose					36:42	high mannose	31:42	high mannose	31:42	An efficient method to control high mannose and core fucose levels in glycosylated antibody production using deoxymannojirimycin.
29673624	8	122	theme	#	1366:1366	arg1	level					1381:1385	IgG1 #A core fucose level	1361:1385	IgG1 #A core fucose level	1361:1385	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	2	123	theme	profile	403:409	arg1	adjustment					371:380	adjustment	371:380	adjustment of the glycosylation profile	371:409	During the development of biosimilar therapeutics, adjustment of the glycosylation profile is required in order to match the reference innovator profile.
29673624	2	124	theme	reference	445:453	arg1	profile					465:471	the reference innovator profile	441:471	the reference innovator profile	441:471	During the development of biosimilar therapeutics, adjustment of the glycosylation profile is required in order to match the reference innovator profile.
29673624	8	125	theme	core	1369:1372	arg1	level					1381:1385	IgG1 #A core fucose level	1361:1385	IgG1 #A core fucose level	1361:1385	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	4	126	theme	#	771:771	arg1	A					772:772	IgG1 #A	766:772	IgG1 #A	766:772	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	1	127	theme	molecule	310:317	arg1	efficacy					283:290	efficacy	283:290	efficacy	283:290	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	1	127	theme	molecule	310:317	arg1	safety					296:301	safety	296:301	safety	296:301	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	8	128	theme	mannose	1422:1428	arg1	level					1430:1434	high mannose level	1417:1434	high mannose level	1417:1434	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	6	129	theme	highest	986:992	arg1	concentration					994:1006	the highest concentration	982:1006	the highest concentration tested	982:1013	At the highest concentration tested, DMJ reduced N-linked complex glycoform and core fucose levels by 15 and 14 fold, respectively, and increased high mannose level by 21 fold.
29673624	9	130	theme	scale	1545:1549	arg1	bioreactors					1551:1561	lab scale bioreactors	1541:1561	lab scale bioreactors	1541:1561	Core fucose level of IgG1 #B in CHOK1SV was decreased from 81% to 73% using 10 μM DMJ in lab scale bioreactors while high mannose was increased from 6% to 15%.
29673624	8	131	theme	95	1392:1393	arg1	%					1394:1394	%	1394:1394	%	1394:1394	Furthermore, in lab scale bioreactors, 15 μM DMJ decreased IgG1 #A core fucose level from 95% to 84% and increased high mannose level from 3% to 13%.
29673624	4	132	theme	different	750:758	arg1	bioreactors					913:923	two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors	746:923	two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors	746:923	The effect of DMJ, at concentrations of 5 μM - 500 μM, on non-fucosylated glycoform levels was tested in the biosynthesis processes of two different IgG1 (IgG1 #A and IgG1 #B) using two Chinese hamster ovary (CHO) cell lines (CHO-DXB-11 and CHOK1SV, respectively) in Erlenmeyer flasks and in lab scale bioreactors.
29673624	2	133	theme	therapeutics	357:368	arg1	development					331:341	the development	327:341	the development of biosimilar therapeutics	327:368	During the development of biosimilar therapeutics, adjustment of the glycosylation profile is required in order to match the reference innovator profile.
29673624	1	134	theme	protein	236:242	arg1	Glycosylation					130:142	Glycosylation	130:142	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies	130:220	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
29673624	1	134	theme	protein	236:242	arg1	attribute					252:260	a critical protein quality attribute	225:260	a critical protein quality attribute which may affect the efficacy and safety of the molecule	225:317	Glycosylation on the Fc region of recombinant Immunoglobulin G (IgG) therapeutic antibodies is a critical protein quality attribute which may affect the efficacy and safety of the molecule.
30532249	5	0	theme	CDHR3	777:781	arg1	immunoprecipitations					783:802	CDHR3 immunoprecipitations	777:802	CDHR3 immunoprecipitations from transfected or transduced cell lysates	777:846	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	3	1	theme	cadherin-related	463:478	arg1	CDHR3					497:501	CDHR3	497:501	CDHR3	497:501	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	1	theme	cadherin-related	463:478	arg1	receptor					436:443	The RV-C receptor	427:443	The RV-C receptor	427:443	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	1	theme	cadherin-related	463:478	arg1	protein					507:513	a protein	505:513	a protein unique to the airway epithelium	505:545	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	1	theme	cadherin-related	463:478	arg1	member					487:492	human cadherin-related family member 3	457:494	human cadherin-related family member 3 (CDHR3)	457:502	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	8	2	from	junctions	1340:1348	arg1	removal					1262:1268	removal	1262:1268	removal	1262:1268	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	8	2	from	junctions	1340:1348	arg1	dilution					1278:1285	even dilution	1273:1285	even dilution	1273:1285	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	7	3	theme	N-linked	1082:1089	arg1	sites					1104:1108	3 extracellular N-linked modification sites	1066:1108	3 extracellular N-linked modification sites	1066:1108	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	3	4	theme	human	457:461	arg1	CDHR3					497:501	CDHR3	497:501	CDHR3	497:501	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	4	theme	human	457:461	arg1	receptor					436:443	The RV-C receptor	427:443	The RV-C receptor	427:443	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	4	theme	human	457:461	arg1	protein					507:513	a protein	505:513	a protein unique to the airway epithelium	505:545	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	4	theme	human	457:461	arg1	member					487:492	human cadherin-related family member 3	457:494	human cadherin-related family member 3 (CDHR3)	457:502	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	1	5	theme	asthma	243:248	arg1	exacerbations					250:262	asthma exacerbations	243:262	asthma exacerbations	243:262	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	8	6	theme	modifications	1208:1220	arg1	None					1194:1197	None	1194:1197	None of these modifications	1194:1220	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	1	7	theme	C	171:171	arg1	species					173:179	the rhinovirus C species	156:179	the rhinovirus C species (RV-C)	156:186	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	1	7	theme	C	171:171	arg1	RV-C					182:185	RV-C	182:185	RV-C	182:185	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	3	8	theme	unique	515:520	arg1	protein					507:513	a protein	505:513	a protein unique to the airway epithelium	505:545	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	8	theme	unique	515:520	arg1	member					487:492	human cadherin-related family member 3	457:494	human cadherin-related family member 3 (CDHR3)	457:502	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	9	9	theme	bacterial	1434:1442	arg1	proteins					1456:1463	bacterial recombinant proteins	1434:1463	bacterial recombinant proteins	1434:1463	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	8	10	theme	RV-C	1240:1243	arg1	recognition					1245:1255	RV-C recognition	1240:1255	RV-C recognition	1240:1255	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	8	11	theme	EC	1337:1338	arg1	junctions					1340:1348	the EC junctions	1333:1348	the EC junctions	1333:1348	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	6	12	theme	Y529	922:925	arg1	variations					927:936	The C529 and Y529 variations	909:936	The C529 and Y529 variations	909:936	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	10	13	theme	receptor	1605:1612	arg1	interactions					1614:1625	virus:receptor interactions	1599:1625	virus:receptor interactions	1599:1625	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	0	14	theme	virus	128:132	arg1	infection					134:142	virus infection	128:142	virus infection	128:142	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	5	15	theme	transfected	809:819	arg1	lysates					840:846	transfected or transduced cell lysates	809:846	transfected or transduced cell lysates	809:846	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	6	16	theme	C529	913:916	arg1	variations					927:936	The C529 and Y529 variations	909:936	The C529 and Y529 variations	909:936	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	10	17	theme	virus	1599:1603	arg1	interactions					1614:1625	virus:receptor interactions	1599:1625	virus:receptor interactions	1599:1625	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	9	18	theme	amino-terminal	1477:1490	arg1	contact					1523:1529	the required virus contact	1504:1529	the required virus contact	1504:1529	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	9	18	theme	amino-terminal	1477:1490	arg1	unit					1496:1499	the amino-terminal EC1 unit	1473:1499	the amino-terminal EC1 unit	1473:1499	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	8	19	theme	even	1273:1276	arg1	dilution					1278:1285	even dilution	1273:1285	even dilution	1273:1285	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	5	20	theme	interaction	883:893	arg1	requirements					895:906	the RV-C interaction requirements	874:906	the RV-C interaction requirements	874:906	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	11	21	theme	CDHR3	1874:1878	arg1	formats					1863:1869	putative EC3-mediated multimerization formats	1825:1869	putative EC3-mediated multimerization formats of CDHR3	1825:1878	We propose that all RV-C use the same EC1 landing pad, interacting with putative EC3-mediated multimerization formats of CDHR3.
30532249	1	22	theme	RV-A	305:308	arg1	isolates					289:296	related isolates	281:296	related isolates of the RV-A or RV-B	281:316	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	7	23	dep	surface-dependent	1132:1148	arg1	α2-6					1151:1154	α2-6	1151:1154	α2-6	1151:1154	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	4	24	theme	display	632:638	arg1	density					640:646	the display density	628:646	the display density of CDHR3 on cell surfaces	628:672	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	1	25	theme	RV-B	313:316	arg1	isolates					289:296	related isolates	281:296	related isolates of the RV-A or RV-B	281:316	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	9	26	theme	virus	1517:1521	arg1	contact					1523:1529	the required virus contact	1504:1529	the required virus contact	1504:1529	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	9	26	theme	virus	1517:1521	arg1	unit					1496:1499	the amino-terminal EC1 unit	1473:1499	the amino-terminal EC1 unit	1473:1499	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	8	27	theme	ions	1323:1326	arg1	removal					1262:1268	removal	1262:1268	removal	1262:1268	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	8	27	theme	ions	1323:1326	arg1	dilution					1278:1285	even dilution	1273:1285	even dilution	1273:1285	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	0	28	theme	recombinant	85:95	arg1	derivatives					97:107	recombinant derivatives	85:107	recombinant derivatives	85:107	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	6	29	theme	repeat	955:960	arg1	domain					962:967	extracellular repeat domain 5	941:969	extracellular repeat domain 5 (EC5)	941:975	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	6	29	theme	repeat	955:960	arg1	EC5					972:974	EC5	972:974	EC5	972:974	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	7	30	link	N-linked	1082:1089	arg1	sites					1104:1108	3 extracellular N-linked modification sites	1066:1108	3 extracellular N-linked modification sites	1066:1108	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	4	31	theme	known	701:705	arg1	correlates					715:724	the strongest known genetic correlates	687:724	the strongest known genetic correlates for childhood virus-induced asthma susceptibility	687:774	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	2	32	theme	other	365:369	arg1	rhinoviruses					371:382	other rhinoviruses	365:382	other rhinoviruses	365:382	The RV-C capsid is structurally distinct from other rhinoviruses and does not bind ICAM-1 or LDL receptors.
30532249	9	33	theme	HeLa	1417:1420	arg1	cells					1422:1426	HeLa cells	1417:1426	HeLa cells	1417:1426	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	10	34	contain	containing	1544:1553	arg1	Derivatives					1532:1542	Derivatives	1532:1542	Derivatives	1532:1542	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	34	contain	containing	1544:1553	arg2	domain					1563:1568	the EC1 domain	1555:1568	the EC1 domain	1555:1568	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	2	35	theme	LDL	412:414	arg1	receptors					416:424	LDL receptors	412:424	LDL receptors	412:424	The RV-C capsid is structurally distinct from other rhinoviruses and does not bind ICAM-1 or LDL receptors.
30532249	0	36	theme	CDHR3	0:4	arg1	domains					20:26	CDHR3 extracellular domains EC1-3	0:32	CDHR3 extracellular domains EC1-3	0:32	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	6	37	from	variations	927:936	arg1	domain					962:967	extracellular repeat domain 5	941:969	extracellular repeat domain 5 (EC5)	941:975	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	6	37	from	variations	927:936	arg1	EC5					972:974	EC5	972:974	EC5	972:974	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	10	38	theme	RV-C	1663:1666	arg1	infection					1668:1676	RV-C infection	1663:1676	RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45)	1663:1750	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	4	39	theme	asthma	754:759	arg1	susceptibility					761:774	childhood virus-induced asthma susceptibility	730:774	childhood virus-induced asthma susceptibility	730:774	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	1	40	theme	related	281:287	arg1	isolates					289:296	related isolates	281:296	related isolates of the RV-A or RV-B	281:316	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	10	41	theme	cells	1693:1697	arg1	infection					1668:1676	RV-C infection	1663:1676	RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45)	1663:1750	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	0	42	theme	C	53:53	arg1	interaction					55:65	rhinovirus C interaction	42:65	rhinovirus C interaction with cells	42:76	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	4	43	dep	polymorphism	568:579	arg1	rs6967330					582:590	rs6967330	582:590	rs6967330	582:590	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	11	44	theme	landing	1795:1801	arg1	pad					1803:1805	the same EC1 landing pad	1782:1805	the same EC1 landing pad	1782:1805	We propose that all RV-C use the same EC1 landing pad, interacting with putative EC3-mediated multimerization formats of CDHR3.
30532249	8	45	theme	virus	1373:1377	arg1	binding					1379:1385	virus binding	1373:1385	virus binding	1373:1385	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	0	46	dep	domains	20:26	arg1	EC1-3					28:32	EC1-3	28:32	EC1-3	28:32	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	4	47	theme	childhood	730:738	arg1	asthma					754:759	childhood virus-induced asthma	730:759	childhood virus-induced asthma susceptibility	730:774	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	3	48	theme	family	480:485	arg1	CDHR3					497:501	CDHR3	497:501	CDHR3	497:501	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	48	theme	family	480:485	arg1	receptor					436:443	The RV-C receptor	427:443	The RV-C receptor	427:443	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	48	theme	family	480:485	arg1	protein					507:513	a protein	505:513	a protein unique to the airway epithelium	505:545	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	48	theme	family	480:485	arg1	member					487:492	human cadherin-related family member 3	457:494	human cadherin-related family member 3 (CDHR3)	457:502	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	4	49	from	density	640:646	arg1	surfaces					665:672	cell surfaces	660:672	cell surfaces	660:672	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	4	50	theme	single	550:555	arg1	polymorphism					568:579	A single nucleotide polymorphism	548:579	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3	548:616	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	7	51	theme	modification	1091:1102	arg1	sites					1104:1108	3 extracellular N-linked modification sites	1066:1108	3 extracellular N-linked modification sites	1066:1108	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	2	52	theme	RV-C	323:326	arg1	capsid					328:333	The RV-C capsid	319:333	The RV-C capsid	319:333	The RV-C capsid is structurally distinct from other rhinoviruses and does not bind ICAM-1 or LDL receptors.
30532249	2	52	theme	RV-C	323:326	arg1	distinct					351:358	distinct	351:358	distinct	351:358	The RV-C capsid is structurally distinct from other rhinoviruses and does not bind ICAM-1 or LDL receptors.
30532249	1	53	theme	wheezing	220:227	arg1	illnesses					229:237	severe wheezing illnesses	213:237	severe wheezing illnesses	213:237	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	5	54	theme	RV-C	878:881	arg1	requirements					895:906	the RV-C interaction requirements	874:906	the RV-C interaction requirements	874:906	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	7	55	theme	extracellular	1068:1080	arg1	sites					1104:1108	3 extracellular N-linked modification sites	1066:1108	3 extracellular N-linked modification sites	1066:1108	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	8	56	theme	stabilizing	1303:1313	arg1	ions					1323:1326	structurally stabilizing calcium ions	1290:1326	structurally stabilizing calcium ions	1290:1326	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	10	57	theme	EC1	1559:1561	arg1	domain					1563:1568	the EC1 domain	1555:1568	the EC1 domain	1555:1568	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	11	58	theme	same	1786:1789	arg1	pad					1803:1805	the same EC1 landing pad	1782:1805	the same EC1 landing pad	1782:1805	We propose that all RV-C use the same EC1 landing pad, interacting with putative EC3-mediated multimerization formats of CDHR3.
30532249	5	59	theme	transduced	824:833	arg1	lysates					840:846	transfected or transduced cell lysates	809:846	transfected or transduced cell lysates	809:846	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	1	60	theme	rhinovirus	160:169	arg1	species					173:179	the rhinovirus C species	156:179	the rhinovirus C species (RV-C)	156:186	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	1	60	theme	rhinovirus	160:169	arg1	RV-C					182:185	RV-C	182:185	RV-C	182:185	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	7	61	theme	mass	1041:1044	arg1	spectrometry					1046:1057	mass spectrometry	1041:1057	mass spectrometry	1041:1057	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	5	62	theme	cell	835:838	arg1	lysates					840:846	transfected or transduced cell lysates	809:846	transfected or transduced cell lysates	809:846	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	6	63	theme	extracellular	941:953	arg1	domain					962:967	extracellular repeat domain 5	941:969	extracellular repeat domain 5 (EC5)	941:975	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	6	63	theme	extracellular	941:953	arg1	EC5					972:974	EC5	972:974	EC5	972:974	The C529 and Y529 variations in extracellular repeat domain 5 (EC5), bound equivalently to virus.
30532249	0	64	dep	mediate	34:40	arg1	inhibitory					114:123	inhibitory	114:123	inhibitory	114:123	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	9	65	theme	recombinant	1444:1454	arg1	proteins					1456:1463	bacterial recombinant proteins	1434:1463	bacterial recombinant proteins	1434:1463	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	11	66	theme	EC1	1791:1793	arg1	pad					1803:1805	the same EC1 landing pad	1782:1805	the same EC1 landing pad	1782:1805	We propose that all RV-C use the same EC1 landing pad, interacting with putative EC3-mediated multimerization formats of CDHR3.
30532249	7	67	theme	Glycosylase	1007:1017	arg1	treatment					1019:1027	Glycosylase treatment	1007:1027	Glycosylase treatment followed by mass spectrometry	1007:1057	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	3	68	theme	airway	529:534	arg1	epithelium					536:545	the airway epithelium	525:545	the airway epithelium	525:545	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	4	69	from	polymorphism	568:579	arg1	CDHR3					612:616	CDHR3	612:616	CDHR3	612:616	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	5	70	used	used	853:856	arg2	immunoprecipitations					783:802	CDHR3 immunoprecipitations	777:802	CDHR3 immunoprecipitations from transfected or transduced cell lysates	777:846	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	9	71	theme	EC1	1492:1494	arg1	contact					1523:1529	the required virus contact	1504:1529	the required virus contact	1504:1529	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	9	71	theme	EC1	1492:1494	arg1	unit					1496:1499	the amino-terminal EC1 unit	1473:1499	the amino-terminal EC1 unit	1473:1499	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	4	72	theme	CDHR3	651:655	arg1	density					640:646	the display density	628:646	the display density of CDHR3 on cell surfaces	628:672	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	5	73	from	lysates	840:846	arg1	immunoprecipitations					783:802	CDHR3 immunoprecipitations	777:802	CDHR3 immunoprecipitations from transfected or transduced cell lysates	777:846	CDHR3 immunoprecipitations from transfected or transduced cell lysates were used to characterize the RV-C interaction requirements.
30532249	7	74	theme	Y529	1181:1184	arg1	format					1186:1191	the Y529 format	1177:1191	the Y529 format	1177:1191	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	9	75	theme	required	1508:1515	arg1	contact					1523:1529	the required virus contact	1504:1529	the required virus contact	1504:1529	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	9	75	theme	required	1508:1515	arg1	unit					1496:1499	the amino-terminal EC1 unit	1473:1499	the amino-terminal EC1 unit	1473:1499	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
30532249	8	76	theme	calcium	1315:1321	arg1	ions					1323:1326	structurally stabilizing calcium ions	1290:1326	structurally stabilizing calcium ions	1290:1326	None of these modifications were required for RV-C recognition, but removal or even dilution of structurally stabilizing calcium ions from the EC junctions irreversibly abrogated virus binding.
30532249	7	77	theme	unique	1167:1172	arg1	sialyation					1156:1165	surface-dependent, α2-6 sialyation	1132:1165	surface-dependent, α2-6 sialyation unique to the Y529 format	1132:1191	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	1	78	from	Viruses	145:151	arg1	species					173:179	the rhinovirus C species	156:179	the rhinovirus C species (RV-C)	156:186	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	1	78	from	Viruses	145:151	arg1	RV-C					182:185	RV-C	182:185	RV-C	182:185	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	4	79	theme	strongest	691:699	arg1	correlates					715:724	the strongest known genetic correlates	687:724	the strongest known genetic correlates for childhood virus-induced asthma susceptibility	687:774	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	11	80	theme	multimerization	1847:1861	arg1	formats					1863:1869	putative EC3-mediated multimerization formats	1825:1869	putative EC3-mediated multimerization formats of CDHR3	1825:1878	We propose that all RV-C use the same EC1 landing pad, interacting with putative EC3-mediated multimerization formats of CDHR3.
30532249	0	81	theme	extracellular	6:18	arg1	domains					20:26	CDHR3 extracellular domains EC1-3	0:32	CDHR3 extracellular domains EC1-3	0:32	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	4	82	theme	cell	660:663	arg1	surfaces					665:672	cell surfaces	660:672	cell surfaces	660:672	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	11	83	theme	putative	1825:1832	arg1	formats					1863:1869	putative EC3-mediated multimerization formats	1825:1869	putative EC3-mediated multimerization formats of CDHR3	1825:1878	We propose that all RV-C use the same EC1 landing pad, interacting with putative EC3-mediated multimerization formats of CDHR3.
30532249	7	84	theme	surface-dependent	1132:1148	arg1	sialyation					1156:1165	surface-dependent, α2-6 sialyation	1132:1165	surface-dependent, α2-6 sialyation unique to the Y529 format	1132:1191	Glycosylase treatment followed by mass spectrometry mapped 3 extracellular N-linked modification sites, and further detected surface-dependent, α2-6 sialyation unique to the Y529 format.
30532249	1	85	dep	RV-A	305:308	arg1	the					301:303	the	301:303	the	301:303	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	10	86	dep	genotypes	1717:1725	arg1	C41					1738:1740	C41	1738:1740	C41	1738:1740	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	86	dep	genotypes	1717:1725	arg1	C45					1747:1749	C45	1747:1749	C45	1747:1749	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	86	dep	genotypes	1717:1725	arg1	C02					1728:1730	C02	1728:1730	C02	1728:1730	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	86	dep	genotypes	1717:1725	arg1	genotypes					1717:1725	several virus genotypes	1703:1725	several virus genotypes (C02, C15, C41, and C45)	1703:1750	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	3	87	theme	RV-C	431:434	arg1	receptor					436:443	The RV-C receptor	427:443	The RV-C receptor	427:443	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	3	87	theme	RV-C	431:434	arg1	member					487:492	human cadherin-related family member 3	457:494	human cadherin-related family member 3 (CDHR3)	457:502	The RV-C receptor is instead, human cadherin-related family member 3 (CDHR3), a protein unique to the airway epithelium.
30532249	0	88	theme	rhinovirus	42:51	arg1	interaction					55:65	rhinovirus C interaction	42:65	rhinovirus C interaction with cells	42:76	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	11	89	theme	EC3-mediated	1834:1845	arg1	formats					1863:1869	putative EC3-mediated multimerization formats	1825:1869	putative EC3-mediated multimerization formats of CDHR3	1825:1878	We propose that all RV-C use the same EC1 landing pad, interacting with putative EC3-mediated multimerization formats of CDHR3.
30532249	4	90	theme	virus-induced	740:752	arg1	asthma					754:759	childhood virus-induced asthma	730:759	childhood virus-induced asthma susceptibility	730:774	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	10	91	theme	susceptible	1681:1691	arg1	cells					1693:1697	susceptible cells	1681:1697	susceptible cells	1681:1697	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	4	92	theme	genetic	707:713	arg1	correlates					715:724	the strongest known genetic correlates	687:724	the strongest known genetic correlates for childhood virus-induced asthma susceptibility	687:774	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	0	93	with	interaction	55:65	arg1	cells					72:76	cells	72:76	cells	72:76	CDHR3 extracellular domains EC1-3 mediate rhinovirus C interaction with cells and as recombinant derivatives, are inhibitory to virus infection.
30532249	2	94	from	rhinoviruses	371:382	arg1	capsid					328:333	The RV-C capsid	319:333	The RV-C capsid	319:333	The RV-C capsid is structurally distinct from other rhinoviruses and does not bind ICAM-1 or LDL receptors.
30532249	2	94	from	rhinoviruses	371:382	arg1	distinct					351:358	distinct	351:358	distinct	351:358	The RV-C capsid is structurally distinct from other rhinoviruses and does not bind ICAM-1 or LDL receptors.
30532249	10	95	theme	several	1703:1709	arg1	C41					1738:1740	C41	1738:1740	C41	1738:1740	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	95	theme	several	1703:1709	arg1	C45					1747:1749	C45	1747:1749	C45	1747:1749	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	95	theme	several	1703:1709	arg1	C02					1728:1730	C02	1728:1730	C02	1728:1730	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	95	theme	several	1703:1709	arg1	genotypes					1717:1725	several virus genotypes	1703:1725	several virus genotypes (C02, C15, C41, and C45)	1703:1750	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	4	96	theme	nucleotide	557:566	arg1	polymorphism					568:579	A single nucleotide polymorphism	548:579	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3	548:616	A single nucleotide polymorphism (rs6967330, encoding C529Y) in CDHR3 regulates the display density of CDHR3 on cell surfaces and is among the strongest known genetic correlates for childhood virus-induced asthma susceptibility.
30532249	1	97	theme	severe	213:218	arg1	illnesses					229:237	severe wheezing illnesses	213:237	severe wheezing illnesses	213:237	Viruses in the rhinovirus C species (RV-C) are more likely to cause severe wheezing illnesses and asthma exacerbations in children than related isolates of the RV-A or RV-B.
30532249	10	98	theme	virus	1711:1715	arg1	C41					1738:1740	C41	1738:1740	C41	1738:1740	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	98	theme	virus	1711:1715	arg1	C45					1747:1749	C45	1747:1749	C45	1747:1749	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	98	theme	virus	1711:1715	arg1	C02					1728:1730	C02	1728:1730	C02	1728:1730	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	10	98	theme	virus	1711:1715	arg1	genotypes					1717:1725	several virus genotypes	1703:1725	several virus genotypes (C02, C15, C41, and C45)	1703:1750	Derivatives containing the EC1 domain, could not only recapitulate virus:receptor interactions in vitro, but also directly inhibit RV-C infection of susceptible cells for several virus genotypes (C02, C15, C41, and C45).
30532249	9	99	theme	CDHR3	1388:1392	arg1	deletions					1394:1402	CDHR3 deletions	1388:1402	CDHR3 deletions	1388:1402	CDHR3 deletions expressed in HeLa cells or as bacterial recombinant proteins, mapped the amino-terminal EC1 unit as the required virus contact.
32038294	7	0	theme	neutrophil	1497:1506	arg1	infiltration					1508:1519	neutrophil infiltration	1497:1519	neutrophil infiltration in lungs	1497:1528	In addition, LPS increased neutrophil infiltration in lungs and produced significant lethality.
32038294	8	1	theme	vascular	1659:1666	arg1	refractoriness					1668:1681	the vascular refractoriness	1655:1681	the vascular refractoriness to phenylephrine	1655:1698	Treatment with GlcN and ThG reduced systemic inflammation and attenuated hypotension and the vascular refractoriness to phenylephrine, improving survival.
32038294	6	2	theme	interleukin-6	1291:1303	arg1	hypotension					1365:1375	severe hypotension	1358:1375	severe hypotension	1358:1375	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	2	theme	interleukin-6	1291:1303	arg1	hyporesponsiveness					1390:1407	vascular hyporesponsiveness	1381:1407	vascular hyporesponsiveness	1381:1407	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	2	theme	interleukin-6	1291:1303	arg1	levels					1257:1262	increased levels	1247:1262	increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α)	1247:1344	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	1	3	theme	cardiovascular	251:264	arg1	derangements					266:277	cardiovascular derangements	251:277	cardiovascular derangements	251:277	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	11	4	theme	cecal	2168:2172	arg1	ligation					2174:2181	cecal ligation	2168:2181	cecal ligation	2168:2181	Finally, GlcN also increased survival rates in mice submitted to cecal ligation and puncture (CLP), a sepsis model.
32038294	10	5	theme	mesenteric	2011:2020	arg1	arteries					2022:2029	mesenteric arteries	2011:2029	mesenteric arteries	2011:2029	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	9	6	from	activation	1882:1891	arg1	macrophages					1921:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	10	7	theme	subunit	2000:2006	arg1	O-glycosylation					1971:1985	O-glycosylation	1971:1985	O-glycosylation of NF-κB p65 subunit in mesenteric arteries	1971:2029	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	10	8	from	O-glycosylation	1971:1985	arg1	arteries					2022:2029	mesenteric arteries	2011:2029	mesenteric arteries	2011:2029	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	3	9	theme	cardiovascular	611:624	arg1	dysfunction					626:636	cardiovascular dysfunction	611:636	cardiovascular dysfunction	611:636	Here, we investigated whether O-GlcNAc affects the inflammatory response and cardiovascular dysfunction associated with sepsis.
32038294	12	10	from	inflammation	2270:2281	arg1	models					2337:2342	experimental sepsis models	2317:2342	experimental sepsis models	2317:2342	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	11	11	theme	survival	2132:2139	arg1	rates					2141:2145	survival rates	2132:2145	survival rates	2132:2145	Finally, GlcN also increased survival rates in mice submitted to cecal ligation and puncture (CLP), a sepsis model.
32038294	5	12	theme	vascular	1064:1071	arg1	cells					1073:1077	vascular cells	1064:1077	vascular cells	1064:1077	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	9	13	theme	LPS-induced	1749:1759	arg1	production					1761:1770	LPS-induced production	1749:1770	LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages	1749:1831	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	12	14	theme	therapeutic	2393:2403	arg1	intervention					2405:2416	therapeutic intervention	2393:2416	therapeutic intervention	2393:2416	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	4	15	theme	lipopolysaccharide	708:725	arg1	injection					695:703	an intraperitoneal injection	676:703	an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS	676:825	Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS.
32038294	10	16	theme	Ser536	2066:2071	arg1	phosphorylation					2073:2087	reduced Ser536 phosphorylation	2058:2087	reduced Ser536 phosphorylation of NF-κB p65	2058:2100	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	6	17	theme	necrosis	1322:1329	arg1	factor					1331:1336	tumor necrosis factor	1316:1336	tumor necrosis factor (TNF-α)	1316:1344	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	17	theme	necrosis	1322:1329	arg1	TNF-α					1339:1343	TNF-α	1339:1343	TNF-α	1339:1343	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	5	18	theme	cytokines	1035:1043	arg1	pressure					1130:1137	blood pressure	1124:1137	blood pressure	1124:1137	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	18	theme	cytokines	1035:1043	arg1	responsiveness					1089:1102	vascular responsiveness	1080:1102	vascular responsiveness to constrictors	1080:1118	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	18	theme	cytokines	1035:1043	arg1	release					1024:1030	release	1024:1030	release	1024:1030	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	18	theme	cytokines	1035:1043	arg1	production					1009:1018	production	1009:1018	production	1009:1018	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	8	19	with	Treatment	1566:1574	arg1	GlcN					1581:1584	GlcN	1581:1584	GlcN	1581:1584	Treatment with GlcN and ThG reduced systemic inflammation and attenuated hypotension and the vascular refractoriness to phenylephrine, improving survival.
32038294	8	19	with	Treatment	1566:1574	arg1	ThG					1590:1592	ThG	1590:1592	ThG	1590:1592	Treatment with GlcN and ThG reduced systemic inflammation and attenuated hypotension and the vascular refractoriness to phenylephrine, improving survival.
32038294	9	20	theme	cytokines	1788:1796	arg1	production					1761:1770	LPS-induced production	1749:1770	LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages	1749:1831	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	9	20	theme	cytokines	1788:1796	arg1	activation					1882:1891	nuclear transcription factor-kappa B (NF-κB) activation	1837:1891	nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages	1837:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	6	21	theme	inflammatory	1220:1231	arg1	response					1233:1240	a systemic and local inflammatory response	1199:1240	a systemic and local inflammatory response	1199:1240	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	4	22	theme	systemic	773:780	arg1	inflammation					782:793	systemic inflammation	773:793	systemic inflammation	773:793	Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS.
32038294	10	23	theme	p65	2098:2100	arg1	phosphorylation					2073:2087	reduced Ser536 phosphorylation	2058:2087	reduced Ser536 phosphorylation of NF-κB p65	2058:2100	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	1	24	theme	inflammatory	132:143	arg1	syndrome					154:161	a systemic inflammatory response syndrome	121:161	a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction	121:304	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	1	24	theme	inflammatory	132:143	arg1	Sepsis					111:116	Sepsis	111:116	Sepsis	111:116	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	1	24	theme	inflammatory	132:143	arg1	SIRS					164:167	SIRS	164:167	SIRS	164:167	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	9	25	theme	bone	1801:1804	arg1	macrophages					1821:1831	bone marrow-derived macrophages	1801:1831	bone marrow-derived macrophages	1801:1831	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	5	26	theme	blood	1124:1128	arg1	pressure					1130:1137	blood pressure	1124:1137	blood pressure	1124:1137	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	3	27	dep	response	598:605	arg1	the					581:583	the	581:583	the	581:583	Here, we investigated whether O-GlcNAc affects the inflammatory response and cardiovascular dysfunction associated with sepsis.
32038294	2	28	theme	vascular	510:517	arg1	contractility					519:531	vascular contractility	510:531	vascular contractility	510:531	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	0	29	theme	Systemic	70:77	arg1	Syndrome					101:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	Acute Increase in O-GlcNAc Improves Survival in Mice With LPS-Induced Systemic Inflammatory Response Syndrome.
32038294	10	30	gly	O-glycosylation	1971:1985	arg1	subunit					2000:2006	NF-κB p65 subunit	1990:2006	NF-κB p65 subunit	1990:2006	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	10	30	gly	O-glycosylation	1971:1985	arg1	arteries					2022:2029	mesenteric arteries	2011:2029	mesenteric arteries	2011:2029	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	9	31	from	production	1761:1770	arg1	macrophages					1921:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	9	32	theme	nuclear	1837:1843	arg1	NF-κB					1875:1879	NF-κB	1875:1879	NF-κB	1875:1879	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	9	32	theme	nuclear	1837:1843	arg1	B					1872:1872	nuclear transcription factor-kappa B	1837:1872	nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages	1837:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	5	33	dep	thiamet-G	946:954	arg1	i.v.					973:976	i.v.	973:976	i.v.	973:976	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	33	dep	thiamet-G	946:954	arg1	μg/Kg					966:970	ThG, 150 μg/Kg	957:970	μg/Kg	966:970	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	0	34	theme	Response	92:99	arg1	Syndrome					101:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	Acute Increase in O-GlcNAc Improves Survival in Mice With LPS-Induced Systemic Inflammatory Response Syndrome.
32038294	9	35	theme	factor-kappa	1859:1870	arg1	NF-κB					1875:1879	NF-κB	1875:1879	NF-κB	1875:1879	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	9	35	theme	factor-kappa	1859:1870	arg1	B					1872:1872	nuclear transcription factor-kappa B	1837:1872	nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages	1837:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	12	36	theme	experimental	2317:2328	arg1	models					2337:2342	experimental sepsis models	2317:2342	experimental sepsis models	2317:2342	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	2	37	theme	processes	413:421	arg1	processes					413:421	the key processes	405:421	the key processes	405:421	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	2	37	theme	processes	413:421	arg1	production					469:478	the production	465:478	the production of inflammatory mediators and vascular contractility	465:531	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	2	37	theme	processes	413:421	arg1	many					397:400	many	397:400	many	397:400	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	0	38	theme	Acute	0:4	arg1	Increase					6:13	Acute Increase	0:13	Acute Increase in O-GlcNAc	0:25	Acute Increase in O-GlcNAc Improves Survival in Mice With LPS-Induced Systemic Inflammatory Response Syndrome.
32038294	4	39	theme	sepsis-induced	807:820	arg1	SIRS					822:825	sepsis-induced SIRS	807:825	sepsis-induced SIRS	807:825	Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS.
32038294	2	40	theme	mediators	496:504	arg1	production					469:478	the production	465:478	the production of inflammatory mediators and vascular contractility	465:531	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	5	41	with	treatment	884:892	arg1	thiamet-G					946:954	thiamet-G	946:954	thiamet-G (ThG, 150 μg/Kg, i.v.)	946:977	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	41	with	treatment	884:892	arg1	glucosamine					907:917	glucosamine	907:917	glucosamine (GlcN, 300 mg/Kg, i.v.)	907:941	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	2	42	theme	inflammatory	483:494	arg1	mediators					496:504	inflammatory mediators	483:504	inflammatory mediators	483:504	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	10	43	dep	increased	1961:1969	arg1	associated					2042:2051	associated	2042:2051	was associated with reduced Ser536 phosphorylation of NF-κB p65	2038:2100	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	2	44	theme	contractility	519:531	arg1	production					469:478	the production	465:478	the production of inflammatory mediators and vascular contractility	465:531	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	5	45	dep	glucosamine	907:917	arg1	i.v.					937:940	i.v.	937:940	i.v.	937:940	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	45	dep	glucosamine	907:917	arg1	mg/Kg					930:934	GlcN, 300 mg/Kg	920:934	mg/Kg	930:934	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	6	46	theme	vascular	1381:1388	arg1	hyporesponsiveness					1390:1407	vascular hyporesponsiveness	1381:1407	vascular hyporesponsiveness	1381:1407	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	9	47	theme	promoter	1912:1919	arg1	macrophages					1921:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	8	48	theme	systemic	1602:1609	arg1	inflammation					1611:1622	systemic inflammation	1602:1622	systemic inflammation	1602:1622	Treatment with GlcN and ThG reduced systemic inflammation and attenuated hypotension and the vascular refractoriness to phenylephrine, improving survival.
32038294	2	49	theme	O-linked	339:346	arg1	N-acetylglucosamine					348:366	O-linked N-acetylglucosamine	339:366	O-linked N-acetylglucosamine (O-GlcNAcylation)	339:384	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	2	49	theme	O-linked	339:346	arg1	O-GlcNAcylation					369:383	O-GlcNAcylation	369:383	O-GlcNAcylation	369:383	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	5	50	theme	LPS-associated	983:996	arg1	mortality					998:1006	LPS-associated mortality	983:1006	LPS-associated mortality	983:1006	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	12	51	theme	cardiovascular	2287:2300	arg1	disfunction					2302:2312	cardiovascular disfunction	2287:2312	cardiovascular disfunction	2287:2312	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	1	52	theme	immune	229:234	arg1	dysregulation					236:248	immune dysregulation	229:248	immune dysregulation	229:248	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	6	53	theme	severe	1358:1363	arg1	hypotension					1365:1375	severe hypotension	1358:1375	severe hypotension	1358:1375	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	12	54	theme	increased	2234:2242	arg1	O-GlcNAc					2244:2251	increased O-GlcNAc	2234:2251	increased O-GlcNAc	2234:2251	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	12	55	from	disfunction	2302:2312	arg1	models					2337:2342	experimental sepsis models	2317:2342	experimental sepsis models	2317:2342	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	5	56	theme	increase	852:859	arg1	effects					832:838	The effects	828:838	The effects of an acute increase in O-GlcNAcylation	828:878	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	6	57	theme	LPS-induced	1172:1182	arg1	SIRS					1184:1187	LPS-induced SIRS	1172:1187	LPS-induced SIRS	1172:1187	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	10	58	theme	p65	1996:1998	arg1	subunit					2000:2006	NF-κB p65 subunit	1990:2006	NF-κB p65 subunit	1990:2006	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	6	59	theme	interleukin-1β	1267:1280	arg1	hypotension					1365:1375	severe hypotension	1358:1375	severe hypotension	1358:1375	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	59	theme	interleukin-1β	1267:1280	arg1	hyporesponsiveness					1390:1407	vascular hyporesponsiveness	1381:1407	vascular hyporesponsiveness	1381:1407	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	59	theme	interleukin-1β	1267:1280	arg1	levels					1257:1262	increased levels	1247:1262	increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α)	1247:1344	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	2	60	theme	proteins	327:334	arg1	modification					311:322	The modification	307:322	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation)	307:384	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	5	61	theme	GlcN	920:923	arg1	i.v.					937:940	i.v.	937:940	i.v.	937:940	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	61	theme	GlcN	920:923	arg1	mg/Kg					930:934	GlcN, 300 mg/Kg	920:934	mg/Kg	930:934	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	3	62	theme	inflammatory	585:596	arg1	response					598:605	inflammatory response	585:605	inflammatory response	585:605	Here, we investigated whether O-GlcNAc affects the inflammatory response and cardiovascular dysfunction associated with sepsis.
32038294	1	63	theme	severe	187:192	arg1	infection					194:202	a severe infection	185:202	a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction	185:304	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	9	64	link	marrow-derived	1806:1819	arg1	macrophages					1821:1831	bone marrow-derived macrophages	1801:1831	bone marrow-derived macrophages	1801:1831	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	4	65	theme	intraperitoneal	679:693	arg1	injection					695:703	an intraperitoneal injection	676:703	an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS	676:825	Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS.
32038294	6	66	theme	factor	1331:1336	arg1	hypotension					1365:1375	severe hypotension	1358:1375	severe hypotension	1358:1375	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	66	theme	factor	1331:1336	arg1	hyporesponsiveness					1390:1407	vascular hyporesponsiveness	1381:1407	vascular hyporesponsiveness	1381:1407	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	66	theme	factor	1331:1336	arg1	levels					1257:1262	increased levels	1247:1262	increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α)	1247:1344	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	5	67	theme	mice	897:900	arg1	treatment					884:892	treatment	884:892	treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.)	884:977	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	6	68	theme	increased	1247:1255	arg1	levels					1257:1262	increased levels	1247:1262	increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α)	1247:1344	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	10	69	theme	reduced	2058:2064	arg1	phosphorylation					2073:2087	reduced Ser536 phosphorylation	2058:2087	reduced Ser536 phosphorylation of NF-κB p65	2058:2100	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	6	70	theme	tumor	1316:1320	arg1	factor					1331:1336	tumor necrosis factor	1316:1336	tumor necrosis factor (TNF-α)	1316:1344	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	6	70	theme	tumor	1316:1320	arg1	TNF-α					1339:1343	TNF-α	1339:1343	TNF-α	1339:1343	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	5	71	theme	vascular	1080:1087	arg1	responsiveness					1089:1102	vascular responsiveness	1080:1102	vascular responsiveness to constrictors	1080:1118	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	9	72	theme	inflammatory	1775:1786	arg1	cytokines					1788:1796	inflammatory cytokines	1775:1796	inflammatory cytokines	1775:1796	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	12	73	theme	potential	2372:2380	arg1	target					2382:2387	a potential target	2370:2387	a potential target for therapeutic intervention	2370:2416	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	12	73	theme	potential	2372:2380	arg1	pathway					2359:2365	this pathway	2354:2365	this pathway	2354:2365	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	4	74	theme	endotoxic	753:761	arg1	shock					763:767	endotoxic shock	753:767	endotoxic shock	753:767	Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS.
32038294	5	75	from	effects	832:838	arg1	O-GlcNAcylation					864:878	O-GlcNAcylation	864:878	O-GlcNAcylation	864:878	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	1	76	theme	systemic	123:130	arg1	syndrome					154:161	a systemic inflammatory response syndrome	121:161	a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction	121:304	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	1	76	theme	systemic	123:130	arg1	Sepsis					111:116	Sepsis	111:116	Sepsis	111:116	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	1	76	theme	systemic	123:130	arg1	SIRS					164:167	SIRS	164:167	SIRS	164:167	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	6	77	theme	local	1214:1218	arg1	response					1233:1240	a systemic and local inflammatory response	1199:1240	a systemic and local inflammatory response	1199:1240	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	10	78	theme	NF-κB	2092:2096	arg1	p65					2098:2100	NF-κB p65	2092:2100	NF-κB p65	2092:2100	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	0	79	theme	LPS-Induced	58:68	arg1	Syndrome					101:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	Acute Increase in O-GlcNAc Improves Survival in Mice With LPS-Induced Systemic Inflammatory Response Syndrome.
32038294	1	80	theme	response	145:152	arg1	syndrome					154:161	a systemic inflammatory response syndrome	121:161	a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction	121:304	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	1	80	theme	response	145:152	arg1	Sepsis					111:116	Sepsis	111:116	Sepsis	111:116	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	1	80	theme	response	145:152	arg1	SIRS					164:167	SIRS	164:167	SIRS	164:167	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	9	81	theme	marrow-derived	1806:1819	arg1	macrophages					1821:1831	bone marrow-derived macrophages	1801:1831	bone marrow-derived macrophages	1801:1831	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	6	82	theme	systemic	1201:1208	arg1	response					1233:1240	a systemic and local inflammatory response	1199:1240	a systemic and local inflammatory response	1199:1240	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	0	83	theme	Inflammatory	79:90	arg1	Syndrome					101:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	Acute Increase in O-GlcNAc Improves Survival in Mice With LPS-Induced Systemic Inflammatory Response Syndrome.
32038294	5	84	from	increase	852:859	arg1	O-GlcNAcylation					864:878	O-GlcNAcylation	864:878	O-GlcNAcylation	864:878	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	0	85	from	Increase	6:13	arg1	O-GlcNAc					18:25	O-GlcNAc	18:25	O-GlcNAc	18:25	Acute Increase in O-GlcNAc Improves Survival in Mice With LPS-Induced Systemic Inflammatory Response Syndrome.
32038294	9	86	theme	transcription	1845:1857	arg1	NF-κB					1875:1879	NF-κB	1875:1879	NF-κB	1875:1879	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	9	86	theme	transcription	1845:1857	arg1	B					1872:1872	nuclear transcription factor-kappa B	1837:1872	nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages	1837:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	12	87	theme	sepsis	2330:2335	arg1	models					2337:2342	experimental sepsis models	2317:2342	experimental sepsis models	2317:2342	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	9	88	theme	B	1872:1872	arg1	activation					1882:1891	nuclear transcription factor-kappa B (NF-κB) activation	1837:1891	nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages	1837:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	2	89	theme	key	409:411	arg1	processes					413:421	the key processes	405:421	the key processes	405:421	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	2	89	theme	key	409:411	arg1	production					469:478	the production	465:478	the production of inflammatory mediators and vascular contractility	465:531	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	5	90	from	O-GlcNAcylation	864:878	arg1	effects					832:838	The effects	828:838	The effects of an acute increase in O-GlcNAcylation	828:878	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	91	theme	ThG	957:959	arg1	i.v.					973:976	i.v.	973:976	i.v.	973:976	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	5	91	theme	ThG	957:959	arg1	μg/Kg					966:970	ThG, 150 μg/Kg	957:970	μg/Kg	966:970	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	6	92	theme	reduced	1427:1433	arg1	vasoconstriction					1435:1450	reduced vasoconstriction	1427:1450	reduced vasoconstriction to phenylephrine	1427:1467	Mice under LPS-induced SIRS exhibited a systemic and local inflammatory response with increased levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), as well as severe hypotension and vascular hyporesponsiveness, characterized by reduced vasoconstriction to phenylephrine.
32038294	1	93	theme	end-organ	284:292	arg1	dysfunction					294:304	end-organ dysfunction	284:304	end-organ dysfunction	284:304	Sepsis is a systemic inflammatory response syndrome (SIRS) resulting from a severe infection that is characterized by immune dysregulation, cardiovascular derangements, and end-organ dysfunction.
32038294	11	94	theme	sepsis	2205:2210	arg1	model					2212:2216	a sepsis model	2203:2216	a sepsis model	2203:2216	Finally, GlcN also increased survival rates in mice submitted to cecal ligation and puncture (CLP), a sepsis model.
32038294	12	95	theme	systemic	2261:2268	arg1	inflammation					2270:2281	systemic inflammation	2261:2281	systemic inflammation	2261:2281	In conclusion, increased O-GlcNAc reduces systemic inflammation and cardiovascular disfunction in experimental sepsis models, pointing this pathway as a potential target for therapeutic intervention.
32038294	4	96	dep	lipopolysaccharide	708:725	arg1	LPS					728:730	LPS	728:730	LPS	728:730	Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS.
32038294	4	96	dep	lipopolysaccharide	708:725	arg1	mg/Kg					736:740	20 mg/Kg	733:740	20 mg/Kg	733:740	Mice received an intraperitoneal injection of lipopolysaccharide (LPS, 20 mg/Kg) to induce endotoxic shock and systemic inflammation, resembling sepsis-induced SIRS.
32038294	9	97	theme	RAW	1896:1898	arg1	macrophages					1921:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	5	98	theme	acute	846:850	arg1	increase					852:859	an acute increase	843:859	an acute increase in O-GlcNAcylation	843:878	The effects of an acute increase in O-GlcNAcylation, by treatment of mice with glucosamine (GlcN, 300 mg/Kg, i.v.) or thiamet-G (ThG, 150 μg/Kg, i.v.), on LPS-associated mortality, production and release of cytokines by macrophages and vascular cells, vascular responsiveness to constrictors and blood pressure were then determined.
32038294	7	99	theme	significant	1543:1553	arg1	lethality					1555:1563	significant lethality	1543:1563	significant lethality	1543:1563	In addition, LPS increased neutrophil infiltration in lungs and produced significant lethality.
32038294	9	100	theme	NF-κB	1906:1910	arg1	macrophages					1921:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	RAW 264.7 NF-κB promoter macrophages	1896:1931	GlcN and ThG also decreased LPS-induced production of inflammatory cytokines by bone marrow-derived macrophages and nuclear transcription factor-kappa B (NF-κB) activation in RAW 264.7 NF-κB promoter macrophages.
32038294	10	101	theme	NF-κB	1990:1994	arg1	subunit					2000:2006	NF-κB p65 subunit	1990:2006	NF-κB p65 subunit	1990:2006	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	10	102	with	Treatment	1934:1942	arg1	ThG					1957:1959	ThG	1957:1959	ThG	1957:1959	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	10	103	theme	mice	1947:1950	arg1	Treatment					1934:1942	Treatment	1934:1942	Treatment of mice with ThG	1934:1959	Treatment of mice with ThG increased O-glycosylation of NF-κB p65 subunit in mesenteric arteries, which was associated with reduced Ser536 phosphorylation of NF-κB p65.
32038294	0	104	with	Mice	48:51	arg1	Syndrome					101:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	LPS-Induced Systemic Inflammatory Response Syndrome	58:108	Acute Increase in O-GlcNAc Improves Survival in Mice With LPS-Induced Systemic Inflammatory Response Syndrome.
32038294	7	105	from	infiltration	1508:1519	arg1	lungs					1524:1528	lungs	1524:1528	lungs	1524:1528	In addition, LPS increased neutrophil infiltration in lungs and produced significant lethality.
32038294	2	106	link	O-linked	339:346	arg1	N-acetylglucosamine					348:366	O-linked N-acetylglucosamine	339:366	O-linked N-acetylglucosamine (O-GlcNAcylation)	339:384	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
32038294	2	106	link	O-linked	339:346	arg1	O-GlcNAcylation					369:383	O-GlcNAcylation	369:383	O-GlcNAcylation	369:383	The modification of proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) influences many of the key processes that are altered during sepsis, including the production of inflammatory mediators and vascular contractility.
31881804	3	0	theme	NSL3	513:516	arg1	NSL3					513:516	NSL3	513:516	NSL3	513:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	0	theme	NSL3	513:516	arg1	site					505:508	the specific modification site	479:508	the specific modification site of NSL3	479:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	0	theme	NSL3	513:516	arg1	mechanism					536:544	its molecular mechanism	522:544	its molecular mechanism of protein stability	522:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	0	theme	NSL3	513:516	arg1	stability					557:565	protein stability	549:565	protein stability	549:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	1	1	theme	crucial	244:250	arg1	NSL3					204:207	NSL3	204:207	NSL3 (nonspecific lethal protein 3)	204:238	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	1	theme	crucial	244:250	arg1	components					252:261	crucial components	244:261	crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex	244:338	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	1	theme	crucial	244:250	arg1	OGT1					129:132	OGT1	129:132	OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1)	129:198	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	9	2	theme	complex	1652:1658	arg1	integrity					1603:1611	integrity	1603:1611	integrity	1603:1611	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	9	2	theme	complex	1652:1658	arg1	activity					1628:1635	holoenzyme activity	1617:1635	holoenzyme activity	1617:1635	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	11	3	theme	mechanism	1902:1910	arg1	elucidation					1873:1883	the elucidation	1869:1883	the elucidation of the molecular mechanism of the MOF/NSL complex	1869:1933	Taken together, our results provide new insight into the elucidation of the molecular mechanism of the MOF/NSL complex.
31881804	7	4	theme	in-depth	1137:1144	arg1	research					1146:1153	Further in-depth research	1129:1153	Further in-depth research	1129:1153	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	3	5	theme	protein	549:555	arg1	stability					557:565	protein stability	549:565	protein stability	549:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	10	6	theme	complex	1724:1730	arg1	integrity					1707:1715	the integrity	1703:1715	the integrity of the complex	1703:1730	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	9	7	theme	histone	1463:1469	arg1	acetylation					1474:1484	histone H4 acetylation	1463:1484	the histone H4 acetylation levels at lysine 5, 8, and 16	1459:1514	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	10	8	theme	lung	1765:1768	arg1	cells					1809:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	5	9	theme	major	893:897	arg1	site					899:902	the major site	889:902	the major site O-GlcNAc-modified by OGT1	889:928	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	5	9	theme	major	893:897	arg1	Thr755					860:865	the residue Thr755	848:865	the residue Thr755 on NSL3 C-terminus	848:884	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	9	10	theme	Thr755	1437:1442	arg1	site					1444:1447	NSL3 Thr755 site	1432:1447	NSL3 Thr755 site	1432:1447	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	10	11	theme	epithelium-like	1788:1802	arg1	cells					1809:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	5	12	theme	NSL3	870:873	arg1	C-terminus					875:884	NSL3 C-terminus	870:884	NSL3 C-terminus	870:884	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	6	13	theme	site	968:971	arg1	O-GlcNAcylation					944:958	O-GlcNAcylation	944:958	O-GlcNAcylation of this site	944:971	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	10	14	theme	type	1780:1783	arg1	cells					1809:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	4	15	theme	MOF/NSL	739:745	arg1	complex					747:753	the MOF/NSL complex	735:753	the MOF/NSL complex	735:753	Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex.
31881804	1	16	theme	O-linked	135:142	arg1	transferase					177:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	135:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1	135:197	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	7	17	theme	direct	1248:1253	arg1	binding					1255:1261	direct binding	1248:1261	direct binding to it	1248:1267	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	10	18	theme	cells	1809:1813	arg1	proliferation					1744:1756	the proliferation	1740:1756	the proliferation of the lung carcinoma type II epithelium-like A549 cells	1740:1813	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	5	19	theme	O-GlcNAc-modified	904:920	arg1	site					899:902	the major site	889:902	the major site O-GlcNAc-modified by OGT1	889:928	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	5	19	theme	O-GlcNAc-modified	904:920	arg1	Thr755					860:865	the residue Thr755	848:865	the residue Thr755 on NSL3 C-terminus	848:884	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	6	20	theme	NSL3	1035:1038	arg1	ubiquitin-degradation					1010:1030	the ubiquitin-degradation	1006:1030	the ubiquitin-degradation of NSL3	1006:1038	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	4	21	theme	holoenzyme	712:721	arg1	activity					723:730	holoenzyme activity	712:730	holoenzyme activity of the MOF/NSL complex	712:753	Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex.
31881804	6	22	gly	O-GlcNAcylation	944:958	arg1	regulation					992:1001	the regulation	988:1001	the regulation of the ubiquitin-degradation of NSL3	988:1038	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	7	23	theme	NSL3	1239:1242	arg1	degradation					1224:1234	the degradation	1220:1234	the degradation of NSL3	1220:1242	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	1	24	theme	histone	306:312	arg1	complex					332:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	6	25	theme	ubiquitin-degradation	1010:1030	arg1	regulation					992:1001	the regulation	988:1001	the regulation of the ubiquitin-degradation of NSL3	988:1038	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	0	26	theme	Histone	90:96	arg1	Complex					115:121	MOF/NSL Histone Acetyltransfease Complex	82:121	MOF/NSL Histone Acetyltransfease Complex	82:121	O-GlcNAc-Modification of NSL3 at Thr755 Site Maintains the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex.
31881804	1	27	theme	complex	332:338	arg1	NSL3					204:207	NSL3	204:207	NSL3 (nonspecific lethal protein 3)	204:238	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	27	theme	complex	332:338	arg1	components					252:261	crucial components	244:261	crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex	244:338	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	27	theme	complex	332:338	arg1	OGT1					129:132	OGT1	129:132	OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1)	129:198	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	11	28	theme	MOF/NSL	1919:1925	arg1	complex					1927:1933	the MOF/NSL complex	1915:1933	the MOF/NSL complex	1915:1933	Taken together, our results provide new insight into the elucidation of the molecular mechanism of the MOF/NSL complex.
31881804	2	29	theme	histone	376:382	arg1	acetylation					387:397	global histone H4 acetylation	369:397	global histone H4 acetylation levels	369:404	We previously described how global histone H4 acetylation levels were modulated by OGT1/O-GlcNAcylation-mediated NSL3 stability.
31881804	5	30	theme	in	762:763	arg1	assays					792:797	in vitro O-GlcNAc-transferase assays	762:797	in vitro O-GlcNAc-transferase assays combined with mass spectrometry	762:829	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	9	31	theme	NSL3	1556:1559	arg1	O-GlcNAcylation					1537:1551	the O-GlcNAcylation	1533:1551	the O-GlcNAcylation of NSL3 at Thr755	1533:1569	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	2	32	theme	NSL3	454:457	arg1	stability					459:467	OGT1/O-GlcNAcylation-mediated NSL3 stability	424:467	OGT1/O-GlcNAcylation-mediated NSL3 stability	424:467	We previously described how global histone H4 acetylation levels were modulated by OGT1/O-GlcNAcylation-mediated NSL3 stability.
31881804	8	33	theme	NSL3	1384:1387	arg1	stability					1389:1397	NSL3 stability	1384:1397	NSL3 stability	1384:1397	Interestingly, OGT1 and UBE2S competitively bind to NSL3, suggesting the coordination of OGT1-UBE2S in regulating NSL3 stability.
31881804	0	34	theme	NSL3	25:28	arg1	O-GlcNAc-Modification					0:20	O-GlcNAc-Modification	0:20	O-GlcNAc-Modification of NSL3 at Thr755 Site	0:43	O-GlcNAc-Modification of NSL3 at Thr755 Site Maintains the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex.
31881804	0	35	theme	Holoenzyme	59:68	arg1	Activity					70:77	the Holoenzyme Activity	55:77	the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex	55:121	O-GlcNAc-Modification of NSL3 at Thr755 Site Maintains the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex.
31881804	2	36	theme	acetylation	387:397	arg1	levels					399:404	global histone H4 acetylation levels	369:404	global histone H4 acetylation levels	369:404	We previously described how global histone H4 acetylation levels were modulated by OGT1/O-GlcNAcylation-mediated NSL3 stability.
31881804	10	37	theme	colony	1664:1669	arg1	assays					1681:1686	colony formation assays	1664:1686	colony formation assays	1664:1686	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	7	38	theme	enzyme	1188:1193	arg1	S					1198:1198	enzyme E2 S	1188:1198	enzyme E2 S (UBE2S)	1188:1206	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	7	38	theme	enzyme	1188:1193	arg1	UBE2S					1201:1205	UBE2S	1201:1205	UBE2S	1201:1205	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	1	39	theme	absent	281:286	arg1	males					275:279	males	275:279	males absent on the first	275:299	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	5	40	theme	mass	813:816	arg1	spectrometry					818:829	mass spectrometry	813:829	mass spectrometry	813:829	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	9	41	from	lysine	1496:1501	arg1	levels					1486:1491	the histone H4 acetylation levels	1459:1491	the histone H4 acetylation levels at lysine 5, 8, and 16	1459:1514	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	6	42	theme	site	1054:1057	arg1	T755A					1069:1073	T755A	1069:1073	T755A	1069:1073	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	6	42	theme	site	1054:1057	arg1	mutation					1059:1066	this site mutation	1049:1066	this site mutation (T755A)	1049:1074	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	5	43	theme	O-GlcNAc-transferase	771:790	arg1	assays					792:797	in vitro O-GlcNAc-transferase assays	762:797	in vitro O-GlcNAc-transferase assays combined with mass spectrometry	762:829	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	1	44	dep	transferase	177:187	arg1	isoform					189:195	isoform 1	189:197	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1	135:197	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	3	45	theme	modification	492:503	arg1	NSL3					513:516	NSL3	513:516	NSL3	513:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	45	theme	modification	492:503	arg1	site					505:508	the specific modification site	479:508	the specific modification site of NSL3	479:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	45	theme	modification	492:503	arg1	stability					557:565	protein stability	549:565	protein stability	549:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	1	46	theme	lethal	222:227	arg1	NSL3					204:207	NSL3	204:207	NSL3 (nonspecific lethal protein 3)	204:238	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	46	theme	lethal	222:227	arg1	protein					229:235	nonspecific lethal protein 3	210:237	nonspecific lethal protein 3	210:237	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	9	47	theme	holoenzyme	1617:1626	arg1	activity					1628:1635	holoenzyme activity	1617:1635	holoenzyme activity	1617:1635	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	2	48	theme	H4	384:385	arg1	acetylation					387:397	global histone H4 acetylation	369:397	global histone H4 acetylation levels	369:404	We previously described how global histone H4 acetylation levels were modulated by OGT1/O-GlcNAcylation-mediated NSL3 stability.
31881804	4	49	theme	NSL3	670:673	arg1	O-GlcNAcylation					651:665	O-GlcNAcylation	651:665	O-GlcNAcylation of NSL3 at Thr755	651:683	Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex.
31881804	6	50	theme	NSL3	1123:1126	arg1	degradation					1108:1118	the ubiquitin-mediated degradation	1085:1118	the ubiquitin-mediated degradation of NSL3	1085:1126	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	4	51	theme	biochemical	614:624	arg1	experiments					626:636	biochemical experiments	614:636	biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex	614:753	Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex.
31881804	11	52	theme	new	1852:1854	arg1	insight					1856:1862	new insight	1852:1862	new insight into the elucidation of the molecular mechanism of the MOF/NSL complex	1852:1933	Taken together, our results provide new insight into the elucidation of the molecular mechanism of the MOF/NSL complex.
31881804	9	53	theme	NSL3	1432:1435	arg1	site					1444:1447	NSL3 Thr755 site	1432:1447	NSL3 Thr755 site	1432:1447	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	9	54	theme	MOF/NSL	1644:1650	arg1	complex					1652:1658	the MOF/NSL complex	1640:1658	the MOF/NSL complex	1640:1658	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	7	55	theme	Further	1129:1135	arg1	research					1146:1153	Further in-depth research	1129:1153	Further in-depth research	1129:1153	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	9	56	theme	site	1444:1447	arg1	O-GlcNAcylation					1413:1427	O-GlcNAcylation	1413:1427	O-GlcNAcylation of NSL3 Thr755 site	1413:1447	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	3	57	theme	molecular	526:534	arg1	mechanism					536:544	its molecular mechanism	522:544	its molecular mechanism of protein stability	522:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	4	58	from	Thr755	678:683	arg1	O-GlcNAcylation					651:665	O-GlcNAcylation	651:665	O-GlcNAcylation of NSL3 at Thr755	651:683	Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex.
31881804	9	59	dep	integrity	1603:1611	arg1	the					1599:1601	the	1599:1601	the	1599:1601	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	10	60	theme	carcinoma	1770:1778	arg1	cells					1809:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	9	61	theme	H4	1471:1472	arg1	acetylation					1474:1484	histone H4 acetylation	1463:1484	the histone H4 acetylation levels at lysine 5, 8, and 16	1459:1514	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	3	62	theme	stability	557:565	arg1	NSL3					513:516	NSL3	513:516	NSL3	513:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	62	theme	stability	557:565	arg1	site					505:508	the specific modification site	479:508	the specific modification site of NSL3	479:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	62	theme	stability	557:565	arg1	mechanism					536:544	its molecular mechanism	522:544	its molecular mechanism of protein stability	522:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	62	theme	stability	557:565	arg1	stability					557:565	protein stability	549:565	protein stability	549:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	5	63	theme	residue	852:858	arg1	site					899:902	the major site	889:902	the major site O-GlcNAc-modified by OGT1	889:928	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	5	63	theme	residue	852:858	arg1	Thr755					860:865	the residue Thr755	848:865	the residue Thr755 on NSL3 C-terminus	848:884	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	10	64	theme	A549	1804:1807	arg1	cells					1809:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	the lung carcinoma type II epithelium-like A549 cells	1761:1813	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	9	65	theme	acetylation	1474:1484	arg1	levels					1486:1491	the histone H4 acetylation levels	1459:1491	the histone H4 acetylation levels at lysine 5, 8, and 16	1459:1514	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	11	66	theme	complex	1927:1933	arg1	mechanism					1902:1910	the molecular mechanism	1888:1910	the molecular mechanism of the MOF/NSL complex	1888:1933	Taken together, our results provide new insight into the elucidation of the molecular mechanism of the MOF/NSL complex.
31881804	5	67	dep	in	762:763	arg1	vitro					765:769	vitro	765:769	vitro	765:769	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	5	68	from	Thr755	860:865	arg1	C-terminus					875:884	NSL3 C-terminus	870:884	NSL3 C-terminus	870:884	Using in vitro O-GlcNAc-transferase assays combined with mass spectrometry, we suppose that the residue Thr755 on NSL3 C-terminus is the major site O-GlcNAc-modified by OGT1.
31881804	4	69	from	experiments	626:636	arg1	evidence					600:607	evidence	600:607	evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex	600:753	Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex.
31881804	1	70	theme	β-N-acetylglucosamine	144:164	arg1	transferase					177:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	135:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1	135:197	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	9	71	from	Thr755	1564:1569	arg1	O-GlcNAcylation					1537:1551	the O-GlcNAcylation	1533:1551	the O-GlcNAcylation of NSL3 at Thr755	1533:1569	Furthermore, O-GlcNAcylation of NSL3 Thr755 site regulates the histone H4 acetylation levels at lysine 5, 8, and 16, suggesting that the O-GlcNAcylation of NSL3 at Thr755 is required for maintaining the integrity and holoenzyme activity of the MOF/NSL complex.
31881804	0	72	theme	MOF/NSL	82:88	arg1	Complex					115:121	MOF/NSL Histone Acetyltransfease Complex	82:121	MOF/NSL Histone Acetyltransfease Complex	82:121	O-GlcNAc-Modification of NSL3 at Thr755 Site Maintains the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex.
31881804	1	73	theme	/NSL	301:304	arg1	complex					332:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	74	theme	O-GlcNAc	167:174	arg1	transferase					177:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	135:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1	135:197	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	0	75	theme	Acetyltransfease	98:113	arg1	Complex					115:121	MOF/NSL Histone Acetyltransfease Complex	82:121	MOF/NSL Histone Acetyltransfease Complex	82:121	O-GlcNAc-Modification of NSL3 at Thr755 Site Maintains the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex.
31881804	1	76	theme	acetyltransferase	314:330	arg1	complex					332:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	6	77	theme	ubiquitin-mediated	1089:1106	arg1	degradation					1108:1118	the ubiquitin-mediated degradation	1085:1118	the ubiquitin-mediated degradation of NSL3	1085:1126	Importantly, O-GlcNAcylation of this site is involved in the regulation of the ubiquitin-degradation of NSL3, because this site mutation (T755A) promotes the ubiquitin-mediated degradation of NSL3.
31881804	0	78	from	Site	40:43	arg1	O-GlcNAc-Modification					0:20	O-GlcNAc-Modification	0:20	O-GlcNAc-Modification of NSL3 at Thr755 Site	0:43	O-GlcNAc-Modification of NSL3 at Thr755 Site Maintains the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex.
31881804	1	79	dep	OGT1	129:132	arg1	transferase					177:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	135:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1	135:197	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	2	80	theme	global	369:374	arg1	acetylation					387:397	global histone H4 acetylation	369:397	global histone H4 acetylation levels	369:404	We previously described how global histone H4 acetylation levels were modulated by OGT1/O-GlcNAcylation-mediated NSL3 stability.
31881804	2	81	theme	OGT1/O-GlcNAcylation-mediated	424:452	arg1	stability					459:467	OGT1/O-GlcNAcylation-mediated NSL3 stability	424:467	OGT1/O-GlcNAcylation-mediated NSL3 stability	424:467	We previously described how global histone H4 acetylation levels were modulated by OGT1/O-GlcNAcylation-mediated NSL3 stability.
31881804	4	82	theme	complex	747:753	arg1	activity					723:730	holoenzyme activity	712:730	holoenzyme activity of the MOF/NSL complex	712:753	Here, we present evidence from biochemical experiments arguing that O-GlcNAcylation of NSL3 at Thr755 is tightly associated with holoenzyme activity of the MOF/NSL complex.
31881804	7	83	theme	E2	1195:1196	arg1	S					1198:1198	enzyme E2 S	1188:1198	enzyme E2 S (UBE2S)	1188:1206	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	7	83	theme	E2	1195:1196	arg1	UBE2S					1201:1205	UBE2S	1201:1205	UBE2S	1201:1205	Further in-depth research found that ubiquitin conjugating enzyme E2 S (UBE2S) accelerated the degradation of NSL3 via direct binding to it.
31881804	1	84	theme	MOF	270:272	arg1	complex					332:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	the MOF (males absent on the first)/NSL histone acetyltransferase complex	266:338	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	10	85	theme	formation	1671:1679	arg1	assays					1681:1686	colony formation assays	1664:1686	colony formation assays	1664:1686	In colony formation assays, we found that the integrity of the complex impacts the proliferation of the lung carcinoma type II epithelium-like A549 cells.
31881804	0	86	theme	Complex	115:121	arg1	Activity					70:77	the Holoenzyme Activity	55:77	the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex	55:121	O-GlcNAc-Modification of NSL3 at Thr755 Site Maintains the Holoenzyme Activity of MOF/NSL Histone Acetyltransfease Complex.
31881804	1	87	dep	complex	332:338	arg1	males					275:279	males	275:279	males absent on the first	275:299	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	88	link	O-linked	135:142	arg1	transferase					177:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	135:187	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1	135:197	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	8	89	theme	OGT1-UBE2S	1359:1368	arg1	coordination					1343:1354	the coordination	1339:1354	the coordination of OGT1-UBE2S in regulating NSL3 stability	1339:1397	Interestingly, OGT1 and UBE2S competitively bind to NSL3, suggesting the coordination of OGT1-UBE2S in regulating NSL3 stability.
31881804	3	90	theme	specific	483:490	arg1	NSL3					513:516	NSL3	513:516	NSL3	513:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	90	theme	specific	483:490	arg1	site					505:508	the specific modification site	479:508	the specific modification site of NSL3	479:516	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	3	90	theme	specific	483:490	arg1	stability					557:565	protein stability	549:565	protein stability	549:565	However, the specific modification site of NSL3 and its molecular mechanism of protein stability remain unknown.
31881804	1	91	theme	nonspecific	210:220	arg1	NSL3					204:207	NSL3	204:207	NSL3 (nonspecific lethal protein 3)	204:238	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	1	91	theme	nonspecific	210:220	arg1	protein					229:235	nonspecific lethal protein 3	210:237	nonspecific lethal protein 3	210:237	Both OGT1 (O-linked β-N-acetylglucosamine (O-GlcNAc) transferase isoform 1) and NSL3 (nonspecific lethal protein 3) are crucial components of the MOF (males absent on the first)/NSL histone acetyltransferase complex.
31881804	11	92	theme	molecular	1892:1900	arg1	mechanism					1902:1910	the molecular mechanism	1888:1910	the molecular mechanism of the MOF/NSL complex	1888:1933	Taken together, our results provide new insight into the elucidation of the molecular mechanism of the MOF/NSL complex.
29659839	7	0	theme	WT	1582:1583	arg1	lungs					1604:1608	WT and CHST1-/- mouse lungs	1582:1608	WT and CHST1-/- mouse lungs	1582:1608	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	2	1	theme	eosinophilic	674:685	arg1	inflammation					694:705	enhanced allergic eosinophilic airway inflammation	656:705	enhanced allergic eosinophilic airway inflammation	656:705	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	3	2	theme	parenchymal	776:786	arg1	cells					788:792	parenchymal cells	776:792	parenchymal cells	776:792	Tissue analysis detected CHST1 expression predominantly not only in parenchymal cells but not in airway epithelium, the latter being a location where Siglec-F ligands are located.
29659839	6	3	theme	airway	1381:1386	arg1	challenge					1388:1396	repeated airway challenge	1372:1396	repeated airway challenge	1372:1396	Eosinophilic airway inflammation was induced in wild-type (WT) and CHST1-/- mice via sensitization to ovalbumin (OVA) and repeated airway challenge.
29659839	2	4	theme	carbohydrate	402:413	arg1	gene					442:445	the carbohydrate sulfotransferase 1 (CHST1) gene	398:445	the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase	398:501	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	2	4	theme	carbohydrate	402:413	arg1	enzyme					507:512	an enzyme	504:512	an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands	504:595	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	2	5	theme	enhanced	656:663	arg1	inflammation					694:705	enhanced allergic eosinophilic airway inflammation	656:705	enhanced allergic eosinophilic airway inflammation	656:705	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	1	6	theme	sialyl	305:310	arg1	N-acetyl-lactosamine					312:331	multivalent sialyl N-acetyl-lactosamine	293:331	6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine	242:331	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	4	7	theme	Siglec-F-Fc	927:937	arg1	proteins					946:953	Siglec-F-Fc fusion proteins	927:953	Siglec-F-Fc fusion proteins	927:953	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	8	8	theme	glycan	1831:1836	arg1	ligands					1838:1844	glycan ligands	1831:1844	glycan ligands for Siglec-F	1831:1857	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	7	9	theme	neutrophils	1503:1513	arg1	challenge					1427:1435	challenge	1427:1435	challenge	1427:1435	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	9	theme	neutrophils	1503:1513	arg1	ligands					1447:1453	Siglec-F ligands	1438:1453	Siglec-F ligands on airway cells	1438:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	9	theme	neutrophils	1503:1513	arg1	sensitization					1409:1421	OVA sensitization	1405:1421	OVA sensitization	1405:1421	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	9	theme	neutrophils	1503:1513	arg1	numbers					1476:1482	numbers	1476:1482	numbers of eosinophils and neutrophils accumulating in the airways	1476:1541	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	1	10	theme	6'-sulfated	211:221	arg1	X					236:236	6'-sulfated sialyl Lewis X	211:236	6'-sulfated sialyl Lewis X	211:236	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	2	11	theme	decreased	614:622	arg1	levels					645:650	decreased Siglec-F lung ligand levels	614:650	decreased Siglec-F lung ligand levels	614:650	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	6	12	theme	airway	1263:1268	arg1	inflammation					1270:1281	Eosinophilic airway inflammation	1250:1281	Eosinophilic airway inflammation	1250:1281	Eosinophilic airway inflammation was induced in wild-type (WT) and CHST1-/- mice via sensitization to ovalbumin (OVA) and repeated airway challenge.
29659839	5	13	theme	bronchoalveolar	1159:1173	arg1	lavage					1175:1180	bronchoalveolar lavage	1159:1180	bronchoalveolar lavage fluid	1159:1186	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	1	14	theme	Lewis	230:234	arg1	X					236:236	6'-sulfated sialyl Lewis X	211:236	6'-sulfated sialyl Lewis X	211:236	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	5	15	link	O-linked	1123:1130	arg1	glycans					1132:1138	the O-linked glycans	1119:1138	the O-linked glycans of lung tissue and bronchoalveolar lavage fluid	1119:1186	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	3	16	theme	Siglec-F	858:865	arg1	ligands					867:873	Siglec-F ligands	858:873	Siglec-F ligands	858:873	Tissue analysis detected CHST1 expression predominantly not only in parenchymal cells but not in airway epithelium, the latter being a location where Siglec-F ligands are located.
29659839	5	17	theme	fluid	1182:1186	arg1	glycans					1132:1138	the O-linked glycans	1119:1138	the O-linked glycans of lung tissue and bronchoalveolar lavage fluid	1119:1186	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	7	18	theme	mouse	1720:1724	arg1	lungs					1726:1730	normal mouse lungs	1713:1730	normal mouse lungs	1713:1730	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	4	19	theme	kDa	982:984	arg1	ligands					1005:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands	964:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs	964:1063	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	2	20	theme	lung	633:636	arg1	levels					645:650	decreased Siglec-F lung ligand levels	614:650	decreased Siglec-F lung ligand levels	614:650	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	4	21	theme	Siglec-F	996:1003	arg1	ligands					1005:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands	964:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs	964:1063	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	6	22	theme	CHST1-/-	1317:1324	arg1	mice					1326:1329	CHST1-/- mice	1317:1329	CHST1-/- mice	1317:1329	Eosinophilic airway inflammation was induced in wild-type (WT) and CHST1-/- mice via sensitization to ovalbumin (OVA) and repeated airway challenge.
29659839	7	23	theme	airway	1458:1463	arg1	cells					1465:1469	airway cells	1458:1469	airway cells	1458:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	5	24	theme	tissue	1148:1153	arg1	glycans					1132:1138	the O-linked glycans	1119:1138	the O-linked glycans of lung tissue and bronchoalveolar lavage fluid	1119:1186	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	3	25	theme	Tissue	708:713	arg1	analysis					715:722	Tissue analysis	708:722	Tissue analysis	708:722	Tissue analysis detected CHST1 expression predominantly not only in parenchymal cells but not in airway epithelium, the latter being a location where Siglec-F ligands are located.
29659839	2	26	theme	putative	564:571	arg1	ligands					589:595	these putative Siglec-F glycan ligands	558:595	these putative Siglec-F glycan ligands	558:595	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	0	27	theme	keratan	70:76	arg1	CHST1					118:122	CHST1	118:122	CHST1	118:122	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	0	27	theme	keratan	70:76	arg1	6-O-sulfotransferase					96:115	keratan sulfate galactose 6-O-sulfotransferase	70:115	keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency	70:134	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	7	28	theme	CHST1-/-	1677:1684	arg1	airway					1692:1697	CHST1-/- mouse airway	1677:1697	CHST1-/- mouse airway	1677:1697	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	4	29	theme	normal	1079:1084	arg1	lungs					1092:1096	normal mouse lungs	1079:1096	normal mouse lungs	1079:1096	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	2	30	theme	Siglec-F	624:631	arg1	levels					645:650	decreased Siglec-F lung ligand levels	614:650	decreased Siglec-F lung ligand levels	614:650	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	0	31	theme	galactose	86:94	arg1	CHST1					118:122	CHST1	118:122	CHST1	118:122	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	0	31	theme	galactose	86:94	arg1	6-O-sulfotransferase					96:115	keratan sulfate galactose 6-O-sulfotransferase	70:115	keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency	70:134	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	1	32	theme	mouse	177:181	arg1	eosinophils					183:193	mouse eosinophils	177:193	mouse eosinophils	177:193	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	5	33	theme	altered	1197:1203	arg1	sialylation					1205:1215	altered sialylation	1197:1215	altered sialylation	1197:1215	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	8	34	theme	airway	1935:1940	arg1	macrophages					1942:1952	airway macrophages	1935:1952	airway macrophages	1935:1952	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	7	35	from	ligands	1447:1453	arg1	cells					1465:1469	airway cells	1458:1469	airway cells	1458:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	2	36	theme	glycan	582:587	arg1	ligands					589:595	these putative Siglec-F glycan ligands	558:595	these putative Siglec-F glycan ligands	558:595	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	7	37	theme	Siglec-F	1438:1445	arg1	ligands					1447:1453	Siglec-F ligands	1438:1453	Siglec-F ligands on airway cells	1438:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	0	38	theme	Airway	0:5	arg1	glycomic					7:14	Airway glycomic	0:14	Airway glycomic	0:14	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	7	39	from	numbers	1476:1482	arg1	cells					1465:1469	airway cells	1458:1469	airway cells	1458:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	2	40	theme	sulfate	464:470	arg1	6-O-sulfotransferase					482:501	keratan sulfate galactose 6-O-sulfotransferase	456:501	keratan sulfate galactose 6-O-sulfotransferase	456:501	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	0	41	theme	inflammatory	29:40	arg1	consequences					42:53	allergic inflammatory consequences	20:53	allergic inflammatory consequences	20:53	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	4	42	theme	extracts	913:920	arg1	blotting					896:903	Western blotting	888:903	Western blotting of lung extracts with Siglec-F-Fc fusion proteins	888:953	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	7	43	theme	mouse	1598:1602	arg1	lungs					1604:1608	WT and CHST1-/- mouse lungs	1582:1608	WT and CHST1-/- mouse lungs	1582:1608	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	5	44	theme	glycans	1132:1138	arg1	Characterization					1099:1114	Characterization	1099:1114	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid	1099:1186	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	4	45	theme	CHST1-/-	1050:1057	arg1	lungs					1059:1063	CHST1-/- lungs	1050:1063	CHST1-/- lungs	1050:1063	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	8	46	theme	keratan	1744:1750	arg1	sulfate					1752:1758	keratan sulfate	1744:1758	keratan sulfate galactose 6-O-sulfotransferase	1744:1789	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	1	47	theme	6'-sulfated	242:252	arg1	N-acetyl-lactosamine					261:280	6'-sulfated sialyl N-acetyl-lactosamine	242:280	6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine	242:331	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	4	48	theme	Western	888:894	arg1	blotting					896:903	Western blotting	888:903	Western blotting of lung extracts with Siglec-F-Fc fusion proteins	888:953	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	8	49	theme	galactose	1760:1768	arg1	6-O-sulfotransferase					1770:1789	keratan sulfate galactose 6-O-sulfotransferase	1744:1789	keratan sulfate galactose 6-O-sulfotransferase	1744:1789	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	1	50	theme	N-acetyl-lactosamine	261:280	arg1	structures					333:342	6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures	211:342	6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures	211:342	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	2	51	theme	sulfotransferase	415:430	arg1	gene					442:445	the carbohydrate sulfotransferase 1 (CHST1) gene	398:445	the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase	398:501	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	2	51	theme	sulfotransferase	415:430	arg1	enzyme					507:512	an enzyme	504:512	an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands	504:595	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	7	52	theme	similar	1564:1570	arg1	degree					1572:1577	a similar degree	1562:1577	a similar degree in WT and CHST1-/- mouse lungs	1562:1608	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	2	53	theme	allergic	665:672	arg1	inflammation					694:705	enhanced allergic eosinophilic airway inflammation	656:705	enhanced allergic eosinophilic airway inflammation	656:705	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	6	54	theme	repeated	1372:1379	arg1	challenge					1388:1396	repeated airway challenge	1372:1396	repeated airway challenge	1372:1396	Eosinophilic airway inflammation was induced in wild-type (WT) and CHST1-/- mice via sensitization to ovalbumin (OVA) and repeated airway challenge.
29659839	8	55	from	synthesis	1818:1826	arg1	airways					1866:1872	the airways	1862:1872	the airways	1862:1872	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	1	56	theme	multivalent	293:303	arg1	N-acetyl-lactosamine					312:331	multivalent sialyl N-acetyl-lactosamine	293:331	6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine	242:331	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	4	57	theme	kDa	969:971	arg1	ligands					1005:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands	964:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs	964:1063	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	3	58	theme	airway	805:810	arg1	epithelium					812:821	airway epithelium	805:821	airway epithelium	805:821	Tissue analysis detected CHST1 expression predominantly not only in parenchymal cells but not in airway epithelium, the latter being a location where Siglec-F ligands are located.
29659839	2	59	theme	airway	687:692	arg1	inflammation					694:705	enhanced allergic eosinophilic airway inflammation	656:705	enhanced allergic eosinophilic airway inflammation	656:705	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	8	60	theme	ligands	1838:1844	arg1	synthesis					1818:1826	the synthesis	1814:1826	the synthesis of glycan ligands for Siglec-F in the airways	1814:1872	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	1	61	theme	sialyl	223:228	arg1	X					236:236	6'-sulfated sialyl Lewis X	211:236	6'-sulfated sialyl Lewis X	211:236	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	6	62	theme	Eosinophilic	1250:1261	arg1	inflammation					1270:1281	Eosinophilic airway inflammation	1250:1281	Eosinophilic airway inflammation	1250:1281	Eosinophilic airway inflammation was induced in wild-type (WT) and CHST1-/- mice via sensitization to ovalbumin (OVA) and repeated airway challenge.
29659839	5	63	theme	lavage	1175:1180	arg1	fluid					1182:1186	bronchoalveolar lavage fluid	1159:1186	bronchoalveolar lavage fluid	1159:1186	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	1	64	theme	X	236:236	arg1	structures					333:342	6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures	211:342	6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures	211:342	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	7	65	from	degree	1572:1577	arg1	lungs					1604:1608	WT and CHST1-/- mouse lungs	1582:1608	WT and CHST1-/- mouse lungs	1582:1608	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	66	theme	normal	1713:1718	arg1	lungs					1726:1730	normal mouse lungs	1713:1730	normal mouse lungs	1713:1730	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	6	67	dep	wild-type	1298:1306	arg1	WT					1309:1310	WT	1309:1310	WT	1309:1310	Eosinophilic airway inflammation was induced in wild-type (WT) and CHST1-/- mice via sensitization to ovalbumin (OVA) and repeated airway challenge.
29659839	2	68	theme	ligand	638:643	arg1	levels					645:650	decreased Siglec-F lung ligand levels	614:650	decreased Siglec-F lung ligand levels	614:650	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	5	69	theme	lung	1143:1146	arg1	tissue					1148:1153	lung tissue	1143:1153	lung tissue	1143:1153	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	7	70	theme	eosinophils	1487:1497	arg1	challenge					1427:1435	challenge	1427:1435	challenge	1427:1435	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	70	theme	eosinophils	1487:1497	arg1	ligands					1447:1453	Siglec-F ligands	1438:1453	Siglec-F ligands on airway cells	1438:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	70	theme	eosinophils	1487:1497	arg1	sensitization					1409:1421	OVA sensitization	1405:1421	OVA sensitization	1405:1421	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	70	theme	eosinophils	1487:1497	arg1	numbers					1476:1482	numbers	1476:1482	numbers of eosinophils and neutrophils accumulating in the airways	1476:1541	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	71	theme	mouse	1686:1690	arg1	airway					1692:1697	CHST1-/- mouse airway	1677:1697	CHST1-/- mouse airway	1677:1697	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	4	72	theme	candidate	986:994	arg1	ligands					1005:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands	964:1011	≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs	964:1063	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	0	73	theme	sulfate	78:84	arg1	CHST1					118:122	CHST1	118:122	CHST1	118:122	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	0	73	theme	sulfate	78:84	arg1	6-O-sulfotransferase					96:115	keratan sulfate galactose 6-O-sulfotransferase	70:115	keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency	70:134	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	1	74	theme	pro-apoptotic	151:163	arg1	receptor					165:172	a pro-apoptotic receptor	149:172	a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays	149:359	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	1	74	theme	pro-apoptotic	151:163	arg1	Siglec-F					137:144	Siglec-F	137:144	Siglec-F	137:144	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	4	75	with	blotting	896:903	arg1	proteins					946:953	Siglec-F-Fc fusion proteins	927:953	Siglec-F-Fc fusion proteins	927:953	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	0	76	theme	6-O-sulfotransferase	96:115	arg1	deficiency					125:134	keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency	70:134	keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency	70:134	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	2	77	theme	some	550:553	arg1	6'-sulfation					534:545	6'-sulfation	534:545	6'-sulfation of some of these putative Siglec-F glycan ligands	534:595	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	8	78	theme	exaggerated	1907:1917	arg1	accumulation					1919:1930	exaggerated accumulation	1907:1930	exaggerated accumulation of airway macrophages and lymphocytes	1907:1968	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	1	79	from	receptor	165:172	arg1	eosinophils					183:193	mouse eosinophils	177:193	mouse eosinophils	177:193	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	2	80	theme	Siglec-F	573:580	arg1	ligands					589:595	these putative Siglec-F glycan ligands	558:595	these putative Siglec-F glycan ligands	558:595	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	2	81	theme	gene	442:445	arg1	attenuation					383:393	attenuation	383:393	attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands,	383:596	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	5	82	theme	minimal	1221:1227	arg1	change					1229:1234	minimal change	1221:1234	minimal change in sulfation	1221:1247	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	8	83	theme	macrophages	1942:1952	arg1	accumulation					1919:1930	exaggerated accumulation	1907:1930	exaggerated accumulation of airway macrophages and lymphocytes	1907:1968	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	2	84	theme	CHST1	435:439	arg1	gene					442:445	the carbohydrate sulfotransferase 1 (CHST1) gene	398:445	the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase	398:501	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	2	84	theme	CHST1	435:439	arg1	enzyme					507:512	an enzyme	504:512	an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands	504:595	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	0	85	theme	allergic	20:27	arg1	consequences					42:53	allergic inflammatory consequences	20:53	allergic inflammatory consequences	20:53	Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.
29659839	8	86	theme	lymphocytes	1958:1968	arg1	accumulation					1919:1930	exaggerated accumulation	1907:1930	exaggerated accumulation of airway macrophages and lymphocytes	1907:1968	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	7	87	theme	OVA	1405:1407	arg1	sensitization					1409:1421	OVA sensitization	1405:1421	OVA sensitization	1405:1421	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	3	88	theme	CHST1	733:737	arg1	expression					739:748	CHST1 expression	733:748	CHST1 expression	733:748	Tissue analysis detected CHST1 expression predominantly not only in parenchymal cells but not in airway epithelium, the latter being a location where Siglec-F ligands are located.
29659839	2	89	theme	galactose	472:480	arg1	6-O-sulfotransferase					482:501	keratan sulfate galactose 6-O-sulfotransferase	456:501	keratan sulfate galactose 6-O-sulfotransferase	456:501	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	1	90	theme	glycan	347:352	arg1	arrays					354:359	glycan arrays	347:359	glycan arrays	347:359	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	4	91	theme	mouse	1086:1090	arg1	lungs					1092:1096	normal mouse lungs	1079:1096	normal mouse lungs	1079:1096	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	2	92	theme	keratan	456:462	arg1	sulfate					464:470	keratan sulfate	456:470	keratan sulfate galactose 6-O-sulfotransferase	456:501	We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation.
29659839	5	93	from	change	1229:1234	arg1	sulfation					1239:1247	sulfation	1239:1247	sulfation	1239:1247	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	5	94	theme	O-linked	1123:1130	arg1	glycans					1132:1138	the O-linked glycans	1119:1138	the O-linked glycans of lung tissue and bronchoalveolar lavage fluid	1119:1186	Characterization of the O-linked glycans of lung tissue and bronchoalveolar lavage fluid detected altered sialylation but minimal change in sulfation.
29659839	4	95	theme	fusion	939:944	arg1	proteins					946:953	Siglec-F-Fc fusion proteins	927:953	Siglec-F-Fc fusion proteins	927:953	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	4	96	theme	lung	908:911	arg1	extracts					913:920	lung extracts	908:920	lung extracts	908:920	Western blotting of lung extracts with Siglec-F-Fc fusion proteins detected ≈500 kDa and ≈200 kDa candidate Siglec-F ligands that were not appreciably altered in CHST1-/- lungs compared with normal mouse lungs.
29659839	8	97	theme	sulfate	1752:1758	arg1	6-O-sulfotransferase					1770:1789	keratan sulfate galactose 6-O-sulfotransferase	1744:1789	keratan sulfate galactose 6-O-sulfotransferase	1744:1789	Therefore, keratan sulfate galactose 6-O-sulfotransferase does not contribute to the synthesis of glycan ligands for Siglec-F in the airways, although its absence results in exaggerated accumulation of airway macrophages and lymphocytes.
29659839	7	98	from	sensitization	1409:1421	arg1	cells					1465:1469	airway cells	1458:1469	airway cells	1458:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	1	99	theme	sialyl	254:259	arg1	N-acetyl-lactosamine					261:280	6'-sulfated sialyl N-acetyl-lactosamine	242:280	6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine	242:331	Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays.
29659839	7	100	theme	CHST1-/-	1589:1596	arg1	lungs					1604:1608	WT and CHST1-/- mouse lungs	1582:1608	WT and CHST1-/- mouse lungs	1582:1608	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
29659839	7	101	from	challenge	1427:1435	arg1	cells					1465:1469	airway cells	1458:1469	airway cells	1458:1469	After OVA sensitization and challenge, Siglec-F ligands on airway cells, and numbers of eosinophils and neutrophils accumulating in the airways, both increased to a similar degree in WT and CHST1-/- mouse lungs, while macrophages and lymphocytes increased significantly more in CHST1-/- mouse airway compared with normal mouse lungs.
31672932	4	0	theme	liver	510:514	arg1	fibrosis					516:523	liver fibrosis	510:523	liver fibrosis	510:523	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	6	1	theme	early	763:767	arg1	age					769:771	an early age	760:771	an early age	760:771	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	6	2	theme	Liver-specific	652:665	arg1	mice					701:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	9	3	theme	spontaneous	1320:1330	arg1	model					1340:1344	an effective spontaneous genetic model	1307:1344	an effective spontaneous genetic model of liver fibrosis	1307:1362	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	3	theme	spontaneous	1320:1330	arg1	mice					1289:1292	OGT-LKO mice	1281:1292	OGT-LKO mice	1281:1292	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	4	theme	genetic	1332:1338	arg1	model					1340:1344	an effective spontaneous genetic model	1307:1344	an effective spontaneous genetic model of liver fibrosis	1307:1362	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	4	theme	genetic	1332:1338	arg1	mice					1289:1292	OGT-LKO mice	1281:1292	OGT-LKO mice	1281:1292	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	7	5	theme	kinase	1024:1029	arg1	levels					950:955	elevated protein expression levels	922:955	elevated protein expression levels	922:955	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	5	theme	kinase	1024:1029	arg1	mediators					1065:1073	key mediators	1061:1073	key mediators of necroptosis	1061:1088	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	6	theme	protein	931:937	arg1	levels					950:955	elevated protein expression levels	922:955	elevated protein expression levels	922:955	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	6	theme	protein	931:937	arg1	mediators					1065:1073	key mediators	1061:1073	key mediators of necroptosis	1061:1088	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	3	7	theme	multiple	351:358	arg1	diseases					366:373	multiple liver diseases	351:373	multiple liver diseases	351:373	Necroptosis has been implicated in multiple liver diseases.
31672932	7	8	theme	domain-like	1031:1041	arg1	kinase					1024:1029	mixed lineage kinase domain-like	1010:1041	mixed lineage kinase domain-like (MLKL)	1010:1048	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	8	theme	domain-like	1031:1041	arg1	MLKL					1044:1047	MLKL	1044:1047	MLKL	1044:1047	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	4	9	theme	O-linked	397:404	arg1	modification					439:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	8	10	theme	RIPK3	1161:1165	arg1	stability					1175:1183	reduced RIPK3 protein stability	1153:1183	reduced RIPK3 protein stability	1153:1183	Furthermore, glycosylation of RIPK3 by OGT is associated with reduced RIPK3 protein stability.
31672932	7	11	theme	expression	939:948	arg1	levels					950:955	elevated protein expression levels	922:955	elevated protein expression levels	922:955	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	11	theme	expression	939:948	arg1	mediators					1065:1073	key mediators	1061:1073	key mediators of necroptosis	1061:1088	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	3	12	theme	liver	360:364	arg1	diseases					366:373	multiple liver diseases	351:373	multiple liver diseases	351:373	Necroptosis has been implicated in multiple liver diseases.
31672932	5	13	theme	ethanol-induced	622:636	arg1	injury					644:649	ethanol-induced liver injury	622:649	ethanol-induced liver injury	622:649	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	7	14	theme	OGT-deficient	850:862	arg1	hepatocytes					864:874	OGT-deficient hepatocytes	850:874	OGT-deficient hepatocytes	850:874	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	5	15	with	patients	565:572	arg1	cirrhosis					595:603	alcoholic liver cirrhosis	579:603	alcoholic liver cirrhosis	579:603	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	9	16	theme	liver	1349:1353	arg1	fibrosis					1355:1362	liver fibrosis	1349:1362	liver fibrosis	1349:1362	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	5	17	theme	liver	638:642	arg1	injury					644:649	ethanol-induced liver injury	622:649	ethanol-induced liver injury	622:649	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	7	18	theme	elevated	922:929	arg1	levels					950:955	elevated protein expression levels	922:955	elevated protein expression levels	922:955	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	18	theme	elevated	922:929	arg1	mediators					1065:1073	key mediators	1061:1073	key mediators of necroptosis	1061:1088	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	9	19	theme	fibrosis	1355:1362	arg1	model					1340:1344	an effective spontaneous genetic model	1307:1344	an effective spontaneous genetic model of liver fibrosis	1307:1362	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	19	theme	fibrosis	1355:1362	arg1	mice					1289:1292	OGT-LKO mice	1281:1292	OGT-LKO mice	1281:1292	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	5	20	theme	liver	589:593	arg1	cirrhosis					595:603	alcoholic liver cirrhosis	579:603	alcoholic liver cirrhosis	579:603	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	9	21	theme	OGT-LKO	1281:1287	arg1	model					1340:1344	an effective spontaneous genetic model	1307:1344	an effective spontaneous genetic model of liver fibrosis	1307:1362	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	21	theme	OGT-LKO	1281:1287	arg1	mice					1289:1292	OGT-LKO mice	1281:1292	OGT-LKO mice	1281:1292	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	7	22	theme	mixed	1010:1014	arg1	kinase					1024:1029	mixed lineage kinase domain-like	1010:1041	mixed lineage kinase domain-like (MLKL)	1010:1048	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	22	theme	mixed	1010:1014	arg1	MLKL					1044:1047	MLKL	1044:1047	MLKL	1044:1047	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	8	23	theme	RIPK3	1121:1125	arg1	glycosylation					1104:1116	glycosylation	1104:1116	glycosylation of RIPK3 by OGT	1104:1132	Furthermore, glycosylation of RIPK3 by OGT is associated with reduced RIPK3 protein stability.
31672932	1	24	theme	billion	82:88	arg1	people					90:95	a billion people	80:95	a billion people	80:95	Worldwide, over a billion people suffer from chronic liver diseases, which often lead to fibrosis and then cirrhosis.
31672932	5	25	theme	Decreased	526:534	arg1	levels					545:550	Decreased O-GlcNAc levels	526:550	Decreased O-GlcNAc levels	526:550	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	0	26	theme	O-GlcNAc	0:7	arg1	transferase					9:19	O-GlcNAc transferase	0:19	O-GlcNAc transferase	0:19	O-GlcNAc transferase suppresses necroptosis and liver fibrosis.
31672932	9	27	theme	hepatocyte	1253:1262	arg1	necroptosis					1264:1274	hepatocyte necroptosis	1253:1274	hepatocyte necroptosis	1253:1274	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	2	28	theme	liver	300:304	arg1	fibrosis					306:313	liver fibrosis	300:313	liver fibrosis	300:313	Treatments for fibrosis remain experimental, in part because no unifying mechanism has been identified that initiates liver fibrosis.
31672932	6	29	theme	portal	810:815	arg1	inflammation					817:828	portal inflammation	810:828	portal inflammation	810:828	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	6	30	theme	age	845:847	arg1	weeks					836:840	10 weeks	833:840	10 weeks of age	833:847	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	7	31	theme	excessive	886:894	arg1	necroptosis					896:906	excessive necroptosis	886:906	excessive necroptosis	886:906	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	32	theme	lineage	1016:1022	arg1	kinase					1024:1029	mixed lineage kinase domain-like	1010:1041	mixed lineage kinase domain-like (MLKL)	1010:1048	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	32	theme	lineage	1016:1022	arg1	MLKL					1044:1047	MLKL	1044:1047	MLKL	1044:1047	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	0	33	theme	liver	48:52	arg1	fibrosis					54:61	liver fibrosis	48:61	liver fibrosis	48:61	O-GlcNAc transferase suppresses necroptosis and liver fibrosis.
31672932	7	34	theme	protein	981:987	arg1	kinase					989:994	receptor-interacting protein kinase 3	960:996	receptor-interacting protein kinase 3 (RIPK3)	960:1004	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	34	theme	protein	981:987	arg1	RIPK3					999:1003	RIPK3	999:1003	RIPK3	999:1003	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	6	35	theme	ballooning	733:742	arg1	degeneration					744:755	ballooning degeneration	733:755	ballooning degeneration	733:755	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	4	36	theme	hepatocyte	469:478	arg1	necroptosis					480:490	hepatocyte necroptosis	469:490	hepatocyte necroptosis	469:490	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	7	37	theme	key	1061:1063	arg1	levels					950:955	elevated protein expression levels	922:955	elevated protein expression levels	922:955	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	37	theme	key	1061:1063	arg1	mediators					1065:1073	key mediators	1061:1073	key mediators of necroptosis	1061:1088	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	9	38	theme	key	1235:1237	arg1	OGT					1226:1228	OGT	1226:1228	OGT	1226:1228	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	38	theme	key	1235:1237	arg1	suppressor					1239:1248	a key suppressor	1233:1248	a key suppressor of hepatocyte necroptosis	1233:1274	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	8	39	theme	reduced	1153:1159	arg1	stability					1175:1183	reduced RIPK3 protein stability	1153:1183	reduced RIPK3 protein stability	1153:1183	Furthermore, glycosylation of RIPK3 by OGT is associated with reduced RIPK3 protein stability.
31672932	1	40	theme	chronic	109:115	arg1	diseases					123:130	chronic liver diseases	109:130	chronic liver diseases	109:130	Worldwide, over a billion people suffer from chronic liver diseases, which often lead to fibrosis and then cirrhosis.
31672932	5	41	with	mice	612:615	arg1	injury					644:649	ethanol-induced liver injury	622:649	ethanol-induced liver injury	622:649	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	9	42	theme	effective	1310:1318	arg1	model					1340:1344	an effective spontaneous genetic model	1307:1344	an effective spontaneous genetic model of liver fibrosis	1307:1362	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	42	theme	effective	1310:1318	arg1	mice					1289:1292	OGT-LKO mice	1281:1292	OGT-LKO mice	1281:1292	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	6	43	theme	liver	791:795	arg1	fibrosis					797:804	liver fibrosis	791:804	liver fibrosis	791:804	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	1	44	theme	liver	117:121	arg1	diseases					123:130	chronic liver diseases	109:130	chronic liver diseases	109:130	Worldwide, over a billion people suffer from chronic liver diseases, which often lead to fibrosis and then cirrhosis.
31672932	4	45	link	O-linked	397:404	arg1	modification					439:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	9	46	theme	necroptosis	1264:1274	arg1	OGT					1226:1228	OGT	1226:1228	OGT	1226:1228	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	9	46	theme	necroptosis	1264:1274	arg1	suppressor					1239:1248	a key suppressor	1233:1248	a key suppressor of hepatocyte necroptosis	1233:1274	Taken together, these findings identify OGT as a key suppressor of hepatocyte necroptosis, and OGT-LKO mice may serve as an effective spontaneous genetic model of liver fibrosis.
31672932	8	47	theme	protein	1167:1173	arg1	stability					1175:1183	reduced RIPK3 protein stability	1153:1183	reduced RIPK3 protein stability	1153:1183	Furthermore, glycosylation of RIPK3 by OGT is associated with reduced RIPK3 protein stability.
31672932	4	48	theme	β-N-acetylglucosamine	406:426	arg1	modification					439:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	2	49	theme	unifying	246:253	arg1	mechanism					255:263	no unifying mechanism	243:263	no unifying mechanism	243:263	Treatments for fibrosis remain experimental, in part because no unifying mechanism has been identified that initiates liver fibrosis.
31672932	5	50	theme	alcoholic	579:587	arg1	cirrhosis					595:603	alcoholic liver cirrhosis	579:603	alcoholic liver cirrhosis	579:603	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	8	51	gly	glycosylation	1104:1116	arg1	RIPK3					1121:1125	RIPK3	1121:1125	RIPK3	1121:1125	Furthermore, glycosylation of RIPK3 by OGT is associated with reduced RIPK3 protein stability.
31672932	6	52	theme	OGT-LKO	692:698	arg1	mice					701:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	7	53	theme	necroptosis	1078:1088	arg1	levels					950:955	elevated protein expression levels	922:955	elevated protein expression levels	922:955	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	53	theme	necroptosis	1078:1088	arg1	mediators					1065:1073	key mediators	1061:1073	key mediators of necroptosis	1061:1088	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	5	54	theme	O-GlcNAc	536:543	arg1	levels					545:550	Decreased O-GlcNAc levels	526:550	Decreased O-GlcNAc levels	526:550	Decreased O-GlcNAc levels were seen in patients with alcoholic liver cirrhosis and in mice with ethanol-induced liver injury.
31672932	7	55	theme	receptor-interacting	960:979	arg1	kinase					989:994	receptor-interacting protein kinase 3	960:996	receptor-interacting protein kinase 3 (RIPK3)	960:1004	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	55	theme	receptor-interacting	960:979	arg1	RIPK3					999:1003	RIPK3	999:1003	RIPK3	999:1003	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	4	56	theme	O-GlcNAc	429:436	arg1	modification					439:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	397:450	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	6	57	theme	transferase-KO	676:689	arg1	mice					701:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
31672932	7	58	theme	kinase	989:994	arg1	levels					950:955	elevated protein expression levels	922:955	elevated protein expression levels	922:955	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	7	58	theme	kinase	989:994	arg1	mediators					1065:1073	key mediators	1061:1073	key mediators of necroptosis	1061:1088	OGT-deficient hepatocytes underwent excessive necroptosis and exhibited elevated protein expression levels of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), which are key mediators of necroptosis.
31672932	4	59	theme	fibrosis	516:523	arg1	initiation					496:505	initiation	496:505	initiation of liver fibrosis	496:523	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	4	59	theme	fibrosis	516:523	arg1	necroptosis					480:490	hepatocyte necroptosis	469:490	hepatocyte necroptosis	469:490	Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) modification protects against hepatocyte necroptosis and initiation of liver fibrosis.
31672932	6	60	theme	O-GlcNAc	667:674	arg1	mice					701:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice	652:704	Liver-specific O-GlcNAc transferase-KO (OGT-LKO) mice exhibited hepatomegaly and ballooning degeneration at an early age and progressed to liver fibrosis and portal inflammation by 10 weeks of age.
30217067	7	0	theme	mRNA	1139:1142	arg1	expression					1144:1153	mRNA expression	1139:1153	mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A	1139:1190	Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A.
30217067	10	1	theme	genes	1455:1459	arg1	expression					1441:1450	the expression	1437:1450	the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway	1437:1516	Both hyperglycemia and metformin induced changes in the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway.
30217067	11	2	from	efficiency	1680:1689	arg1	cells					1728:1732	human ovarian cancer cells	1707:1732	human ovarian cancer cells	1707:1732	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	11	3	theme	HIF1A	1603:1607	arg1	pathway					1609:1615	the related HIF1A pathway	1591:1615	the related HIF1A pathway	1591:1615	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	11	3	theme	HIF1A	1603:1607	arg1	responsible					1640:1650	responsible	1640:1650	responsible	1640:1650	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	1	4	theme	metabolic	256:264	arg1	alteration					266:275	metabolic alteration	256:275	metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways	256:400	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	0	5	theme	Metformin	97:105	arg1	Action					87:92	Anticancer Action	76:92	Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3)	76:138	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	1	6	theme	Hypoxia-inducible	359:375	arg1	O-GlcNAcylation					332:346	O-GlcNAcylation	332:346	O-GlcNAcylation	332:346	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	1	6	theme	Hypoxia-inducible	359:375	arg1	1-alpha					384:390	Hypoxia-inducible factor 1-alpha	359:390	Hypoxia-inducible factor 1-alpha	359:390	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	1	7	theme	more	168:171	arg1	glucose					173:179	more glucose	168:179	more glucose	168:179	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	10	8	from	changes	1426:1432	arg1	expression					1441:1450	the expression	1437:1450	the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway	1437:1516	Both hyperglycemia and metformin induced changes in the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway.
30217067	0	9	theme	Cancer	118:123	arg1	SKOV-3					132:137	SKOV-3	132:137	SKOV-3	132:137	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	0	9	theme	Cancer	118:123	arg1	Cells					125:129	Ovarian Cancer Cells	110:129	Ovarian Cancer Cells (SKOV-3)	110:138	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	1	10	theme	factor	377:382	arg1	O-GlcNAcylation					332:346	O-GlcNAcylation	332:346	O-GlcNAcylation	332:346	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	1	10	theme	factor	377:382	arg1	1-alpha					384:390	Hypoxia-inducible factor 1-alpha	359:390	Hypoxia-inducible factor 1-alpha	359:390	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	8	11	theme	cells	1253:1257	arg1	proliferation					1229:1241	the proliferation	1225:1241	the proliferation of SKOV-3 cells	1225:1257	Metformin significantly reduced the proliferation of SKOV-3 cells under normal glucose conditions.
30217067	0	12	theme	Ovarian	110:116	arg1	SKOV-3					132:137	SKOV-3	132:137	SKOV-3	132:137	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	0	12	theme	Ovarian	110:116	arg1	Cells					125:129	Ovarian Cancer Cells	110:129	Ovarian Cancer Cells (SKOV-3)	110:138	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	11	13	theme	related	1595:1601	arg1	pathway					1609:1615	the related HIF1A pathway	1591:1615	the related HIF1A pathway	1591:1615	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	11	13	theme	related	1595:1601	arg1	responsible					1640:1650	responsible	1640:1650	responsible	1640:1650	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	8	14	theme	SKOV-3	1246:1251	arg1	cells					1253:1257	SKOV-3 cells	1246:1257	SKOV-3 cells	1246:1257	Metformin significantly reduced the proliferation of SKOV-3 cells under normal glucose conditions.
30217067	7	15	theme	OGA	1163:1165	arg1	expression					1144:1153	mRNA expression	1139:1153	mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A	1139:1190	Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A.
30217067	3	16	theme	SKOV-3	566:571	arg1	cells					573:577	SKOV-3 cells	566:577	SKOV-3 cells cultured in hyperglycemia and normoglycemia	566:621	The aim of this study was to determine the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia.
30217067	4	17	theme	hydrolase	754:762	arg1	HIF1A					828:832	HIF1A	828:832	HIF1A	828:832	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	17	theme	hydrolase	754:762	arg1	1-alpha					819:825	hypoxia-inducible factor 1-alpha	794:825	hypoxia-inducible factor 1-alpha (HIF1A)	794:833	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	17	theme	hydrolase	754:762	arg1	expression					677:686	the expression	673:686	the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA)	673:780	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	17	theme	hydrolase	754:762	arg1	transporters					847:858	glucose transporters	839:858	glucose transporters	839:858	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	6	18	theme	necrotic	1055:1062	arg1	death					1076:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	6	18	theme	necrotic	1055:1062	arg1	rate					1035:1038	The proliferation rate	1017:1038	The proliferation rate	1017:1038	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	3	19	from	efficiency	539:548	arg1	cells					573:577	SKOV-3 cells	566:577	SKOV-3 cells cultured in hyperglycemia and normoglycemia	566:621	The aim of this study was to determine the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia.
30217067	4	20	theme	hypoxia-inducible	794:810	arg1	HIF1A					828:832	HIF1A	828:832	HIF1A	828:832	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	20	theme	hypoxia-inducible	794:810	arg1	1-alpha					819:825	hypoxia-inducible factor 1-alpha	794:825	hypoxia-inducible factor 1-alpha (HIF1A)	794:833	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	21	theme	β-N-acetlyglucosamine	700:720	arg1	OGT					735:737	OGT	735:737	OGT	735:737	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	21	theme	β-N-acetlyglucosamine	700:720	arg1	transferase					722:732	O-linked β-N-acetlyglucosamine transferase	691:732	O-linked β-N-acetlyglucosamine transferase (OGT)	691:738	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	9	22	theme	cell	1344:1347	arg1	death					1349:1353	SKOV-3 cell death	1337:1353	SKOV-3 cell death	1337:1353	Whereas, the efficacy of metformin to induce SKOV-3 cell death was reduced in hyperglycemia.
30217067	9	23	theme	SKOV-3	1337:1342	arg1	death					1349:1353	SKOV-3 cell death	1337:1353	SKOV-3 cell death	1337:1353	Whereas, the efficacy of metformin to induce SKOV-3 cell death was reduced in hyperglycemia.
30217067	9	24	theme	metformin	1317:1325	arg1	efficacy					1305:1312	the efficacy	1301:1312	the efficacy of metformin to induce SKOV-3 cell death	1301:1353	Whereas, the efficacy of metformin to induce SKOV-3 cell death was reduced in hyperglycemia.
30217067	0	25	theme	Hyperglycemia-Associated	0:23	arg1	Dysregulation					25:37	Hyperglycemia-Associated Dysregulation	0:37	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A	0:66	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	11	26	theme	human	1707:1711	arg1	cells					1728:1732	human ovarian cancer cells	1707:1732	human ovarian cancer cells	1707:1732	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	5	27	theme	10	979:980	arg1	mM					982:983	mM	982:983	mM	982:983	SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h.
30217067	7	28	theme	HIF1A	1186:1190	arg1	expression					1144:1153	mRNA expression	1139:1153	mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A	1139:1190	Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A.
30217067	7	29	theme	GLUT3	1175:1179	arg1	expression					1144:1153	mRNA expression	1139:1153	mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A	1139:1190	Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A.
30217067	1	30	theme	normal	186:191	arg1	cells					193:197	normal cells	186:197	normal cells	186:197	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	2	31	theme	cell	474:477	arg1	death					479:483	cancer cell death	467:483	cancer cell death	467:483	Metformin was demonstrated to evoke metabolic stress and induce cancer cell death.
30217067	4	32	dep	hydrolase	754:762	arg1	OGA					777:779	OGA	777:779	OGA	777:779	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	32	dep	hydrolase	754:762	arg1	O-GlcNAcase					764:774	O-GlcNAcase	764:774	glycoside hydrolase O-GlcNAcase (OGA)	744:780	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	5	33	dep	hyperglycemia	936:948	arg1	HG					951:952	HG	951:952	HG	951:952	SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h.
30217067	5	33	dep	hyperglycemia	936:948	arg1	mM					958:959	25 mM	955:959	25 mM	955:959	SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h.
30217067	4	34	theme	O-linked	691:698	arg1	OGT					735:737	OGT	735:737	OGT	735:737	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	34	theme	O-linked	691:698	arg1	transferase					722:732	O-linked β-N-acetlyglucosamine transferase	691:732	O-linked β-N-acetlyglucosamine transferase (OGT)	691:738	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	0	35	theme	O-GlcNAcylation	42:56	arg1	Dysregulation					25:37	Hyperglycemia-Associated Dysregulation	0:37	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A	0:66	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	1	36	theme	signaling	298:306	arg1	pathways					308:315	signaling pathways	298:315	signaling pathways	298:315	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	1	36	theme	signaling	298:306	arg1	pathways					393:400	the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways	328:400	the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways	328:400	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	10	37	dep	O-GlcNAcylation	1477:1491	arg1	status					1493:1498	status	1493:1498	status	1493:1498	Both hyperglycemia and metformin induced changes in the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway.
30217067	10	37	dep	O-GlcNAcylation	1477:1491	arg1	pathway					1510:1516	pathway	1510:1516	pathway	1510:1516	Both hyperglycemia and metformin induced changes in the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway.
30217067	6	38	theme	cell	1071:1074	arg1	death					1076:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	6	38	theme	cell	1071:1074	arg1	rate					1035:1038	The proliferation rate	1017:1038	The proliferation rate	1017:1038	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	5	39	dep	normoglycaemia	906:919	arg1	NG					922:923	NG	922:923	NG	922:923	SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h.
30217067	5	39	dep	normoglycaemia	906:919	arg1	mM					928:929	5 mM	926:929	5 mM	926:929	SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h.
30217067	11	40	theme	ovarian	1713:1719	arg1	cells					1728:1732	human ovarian cancer cells	1707:1732	human ovarian cancer cells	1707:1732	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	8	41	theme	normal	1265:1270	arg1	conditions					1280:1289	normal glucose conditions	1265:1289	normal glucose conditions	1265:1289	Metformin significantly reduced the proliferation of SKOV-3 cells under normal glucose conditions.
30217067	6	42	theme	SKOV-3	1064:1069	arg1	death					1076:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	6	42	theme	SKOV-3	1064:1069	arg1	rate					1035:1038	The proliferation rate	1017:1038	The proliferation rate	1017:1038	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	3	43	theme	cytotoxic	529:537	arg1	efficiency					539:548	the cytotoxic efficiency	525:548	the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia	525:621	The aim of this study was to determine the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia.
30217067	0	44	theme	HIF1A	62:66	arg1	Dysregulation					25:37	Hyperglycemia-Associated Dysregulation	0:37	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A	0:66	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	11	45	theme	cancer	1721:1726	arg1	cells					1728:1732	human ovarian cancer cells	1707:1732	human ovarian cancer cells	1707:1732	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	1	46	theme	energy	211:216	arg1	demand					218:223	energy demand	211:223	energy demand	211:223	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	2	47	theme	metabolic	439:447	arg1	stress					449:454	metabolic stress	439:454	metabolic stress	439:454	Metformin was demonstrated to evoke metabolic stress and induce cancer cell death.
30217067	5	48	theme	SKOV-3	876:881	arg1	cells					883:887	SKOV-3 cells	876:887	SKOV-3 cells	876:887	SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h.
30217067	2	49	theme	cancer	467:472	arg1	death					479:483	cancer cell death	467:483	cancer cell death	467:483	Metformin was demonstrated to evoke metabolic stress and induce cancer cell death.
30217067	4	50	dep	1-alpha	819:825	arg1	GLUT3					868:872	GLUT3	868:872	GLUT3	868:872	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	50	dep	1-alpha	819:825	arg1	GLUT1					861:865	GLUT1	861:865	GLUT1	861:865	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	0	51	theme	Anticancer	76:85	arg1	Action					87:92	Anticancer Action	76:92	Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3)	76:138	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	0	52	from	Action	87:92	arg1	SKOV-3					132:137	SKOV-3	132:137	SKOV-3	132:137	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	0	52	from	Action	87:92	arg1	Cells					125:129	Ovarian Cancer Cells	110:129	Ovarian Cancer Cells (SKOV-3)	110:138	Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3).
30217067	5	53	theme	mM	982:983	arg1	metformin					985:993	10 mM metformin	979:993	10 mM metformin	979:993	SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h.
30217067	8	54	theme	glucose	1272:1278	arg1	conditions					1280:1289	normal glucose conditions	1265:1289	normal glucose conditions	1265:1289	Metformin significantly reduced the proliferation of SKOV-3 cells under normal glucose conditions.
30217067	4	55	theme	glycoside	744:752	arg1	hydrolase					754:762	glycoside hydrolase O-GlcNAcase (OGA)	744:780	glycoside hydrolase O-GlcNAcase (OGA)	744:780	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	1	56	theme	O-GlcNAcylation	332:346	arg1	pathways					393:400	the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways	328:400	the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways	328:400	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	11	57	theme	O-GlcNAcylation	1570:1584	arg1	dysregulation					1553:1565	dysregulation	1553:1565	dysregulation of O-GlcNAcylation	1553:1584	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	11	57	theme	O-GlcNAcylation	1570:1584	arg1	responsible					1640:1650	responsible	1640:1650	responsible	1640:1650	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	11	57	theme	O-GlcNAcylation	1570:1584	arg1	pathway					1609:1615	the related HIF1A pathway	1591:1615	the related HIF1A pathway	1591:1615	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	4	58	theme	glucose	839:845	arg1	transporters					847:858	glucose transporters	839:858	glucose transporters	839:858	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	11	59	theme	cytotoxic	1670:1678	arg1	efficiency					1680:1689	the decreased cytotoxic efficiency	1656:1689	the decreased cytotoxic efficiency of metformin in human ovarian cancer cells	1656:1732	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	7	60	theme	GLUT1	1168:1172	arg1	expression					1144:1153	mRNA expression	1139:1153	mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A	1139:1190	Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A.
30217067	7	61	theme	Real-Time	1098:1106	arg1	qPCR					1108:1111	Real-Time qPCR	1098:1111	Real-Time qPCR	1098:1111	Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A.
30217067	4	62	link	O-linked	691:698	arg1	OGT					735:737	OGT	735:737	OGT	735:737	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	62	link	O-linked	691:698	arg1	transferase					722:732	O-linked β-N-acetlyglucosamine transferase	691:732	O-linked β-N-acetlyglucosamine transferase (OGT)	691:738	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	6	63	theme	apoptotic	1041:1049	arg1	death					1076:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	6	63	theme	apoptotic	1041:1049	arg1	rate					1035:1038	The proliferation rate	1017:1038	The proliferation rate	1017:1038	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	11	64	theme	metformin	1694:1702	arg1	efficiency					1680:1689	the decreased cytotoxic efficiency	1656:1689	the decreased cytotoxic efficiency of metformin in human ovarian cancer cells	1656:1732	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	3	65	theme	metformin	553:561	arg1	efficiency					539:548	the cytotoxic efficiency	525:548	the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia	525:621	The aim of this study was to determine the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia.
30217067	4	66	theme	factor	812:817	arg1	HIF1A					828:832	HIF1A	828:832	HIF1A	828:832	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	66	theme	factor	812:817	arg1	1-alpha					819:825	hypoxia-inducible factor 1-alpha	794:825	hypoxia-inducible factor 1-alpha (HIF1A)	794:833	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	3	67	theme	study	502:506	arg1	aim					490:492	The aim	486:492	The aim of this study	486:506	The aim of this study was to determine the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia.
30217067	1	68	theme	chronic	226:232	arg1	hyperglycemia					234:246	chronic hyperglycemia	226:246	chronic hyperglycemia	226:246	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	6	69	theme	proliferation	1021:1033	arg1	death					1076:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	apoptotic and necrotic SKOV-3 cell death	1041:1080	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	6	69	theme	proliferation	1021:1033	arg1	rate					1035:1038	The proliferation rate	1017:1038	The proliferation rate	1017:1038	The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated.
30217067	1	70	theme	cancer	150:155	arg1	cells					157:161	cancer cells	150:161	cancer cells	150:161	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	7	71	theme	OGT	1158:1160	arg1	expression					1144:1153	mRNA expression	1139:1153	mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A	1139:1190	Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A.
30217067	1	72	theme	HIF1A	352:356	arg1	pathways					393:400	the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways	328:400	the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways	328:400	Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways.
30217067	11	73	theme	decreased	1660:1668	arg1	efficiency					1680:1689	the decreased cytotoxic efficiency	1656:1689	the decreased cytotoxic efficiency of metformin in human ovarian cancer cells	1656:1732	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	11	74	theme	obtained	1523:1530	arg1	results					1532:1538	The obtained results	1519:1538	The obtained results	1519:1538	The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
30217067	4	75	theme	transferase	722:732	arg1	HIF1A					828:832	HIF1A	828:832	HIF1A	828:832	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	75	theme	transferase	722:732	arg1	1-alpha					819:825	hypoxia-inducible factor 1-alpha	794:825	hypoxia-inducible factor 1-alpha (HIF1A)	794:833	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	75	theme	transferase	722:732	arg1	expression					677:686	the expression	673:686	the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA)	673:780	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	75	theme	transferase	722:732	arg1	transporters					847:858	glucose transporters	839:858	glucose transporters	839:858	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
30217067	4	76	theme	potential	640:648	arg1	mechanism					650:658	the potential mechanism	636:658	the potential mechanism	636:658	To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3).
31842258	7	0	theme	M6P-tagging	1584:1594	arg1	efficiency					1604:1613	the in planta M6P-tagging process efficiency	1570:1613	the in planta M6P-tagging process efficiency	1570:1613	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	4	1	theme	multi-gene	1080:1089	arg1	construct					1091:1099	a single multi-gene construct	1071:1099	a single multi-gene construct	1071:1099	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	3	2	theme	Recombinant	731:741	arg1	enzyme					743:748	Recombinant enzyme	731:748	Recombinant enzyme in ERT	731:755	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	6	3	theme	putative	1351:1358	arg1	M6P-IDUA					1360:1367	the putative M6P-IDUA	1347:1367	the putative M6P-IDUA	1347:1367	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	7	4	theme	in	1574:1575	arg1	efficiency					1604:1613	the in planta M6P-tagging process efficiency	1570:1613	the in planta M6P-tagging process efficiency	1570:1613	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	7	5	theme	plant-IDUA	1866:1875	arg1	amount					1852:1857	a significant amount	1838:1857	a significant amount of the plant-IDUA	1838:1875	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	7	5	theme	plant-IDUA	1866:1875	arg1	plant-IDUA					1866:1875	the plant-IDUA	1862:1875	the plant-IDUA	1862:1875	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	1	6	from	lysosomes	317:325	arg1	accumulation					266:277	accumulation	266:277	accumulation of non-degraded glycosaminoglycans in lysosomes	266:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	6	7	with	comparable	1411:1420	arg1	efficiency					1431:1440	the efficiency	1427:1440	the efficiency of the purified plant mannose-terminated IDUA	1427:1486	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	5	8	theme	substantial	1275:1285	arg1	reduction					1287:1295	substantial reduction	1275:1295	substantial reduction of glycosaminoglycans	1275:1317	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	1	9	from	glycosaminoglycans	295:312	arg1	lysosomes					317:325	lysosomes	317:325	lysosomes	317:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	1	10	theme	severe	171:176	arg1	I					164:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	1	10	theme	severe	171:176	arg1	disease					196:202	a severe lysosomal storage disease	169:202	a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes	169:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	7	11	theme	significant	1840:1850	arg1	amount					1852:1857	a significant amount	1838:1857	a significant amount of the plant-IDUA	1838:1875	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	7	11	theme	significant	1840:1850	arg1	plant-IDUA					1866:1875	the plant-IDUA	1862:1875	the plant-IDUA	1862:1875	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	8	12	theme	alternative	2012:2022	arg1	strategy					2043:2050	an alternative and cost-effective strategy	2009:2050	an alternative and cost-effective strategy to the conventional ERT	2009:2074	Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif.
31842258	1	13	theme	storage	188:194	arg1	I					164:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	1	13	theme	storage	188:194	arg1	disease					196:202	a severe lysosomal storage disease	169:202	a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes	169:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	0	14	theme	Disorders	125:133	arg1	Therapy					96:102	Enzyme Replacement Therapy	77:102	Enzyme Replacement Therapy of Lysosomal Storage Disorders	77:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	2	15	theme	human	557:561	arg1	IDUA					563:566	recombinant human IDUA	545:566	recombinant human IDUA in seeds of an Arabidopsis mutant	545:600	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	3	16	theme	6-phosphate	799:809	arg1	signal					827:832	a mannose 6-phosphate (M6P) targeting signal	789:832	a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome	789:914	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	5	17	theme	purified	1123:1130	arg1	M6P-IDUA					1141:1148	purified putative M6P-IDUA	1123:1148	purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts	1123:1206	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	2	18	theme	cost-effective	433:446	arg1	alternative					457:467	a more cost-effective and safe alternative	426:467	a more cost-effective and safe alternative to the commercial mammalian cell-based production systems	426:525	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	1	19	theme	α-L-iduronidase	214:228	arg1	deficiency					237:246	α-L-iduronidase (IDUA) deficiency	214:246	α-L-iduronidase (IDUA) deficiency	214:246	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	2	20	theme	Arabidopsis	583:593	arg1	mutant					595:600	an Arabidopsis mutant	580:600	an Arabidopsis mutant	580:600	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	7	21	link	plant-derived	1687:1699	arg1	IDUA					1720:1723	the plant-derived mannose-terminated IDUA	1683:1723	the plant-derived mannose-terminated IDUA	1683:1723	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	6	22	theme	glycosaminoglycan	1381:1397	arg1	storage					1399:1405	glycosaminoglycan storage	1381:1405	glycosaminoglycan storage	1381:1405	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	7	23	theme	plant-derived	1687:1699	arg1	IDUA					1720:1723	the plant-derived mannose-terminated IDUA	1683:1723	the plant-derived mannose-terminated IDUA	1683:1723	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	2	24	theme	N-linked	713:720	arg1	glycans					722:728	predominantly high mannose N-linked glycans	686:728	predominantly high mannose N-linked glycans	686:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	3	25	theme	targeting	817:825	arg1	signal					827:832	a mannose 6-phosphate (M6P) targeting signal	789:832	a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome	789:914	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	8	26	theme	cost-effective	2028:2041	arg1	strategy					2043:2050	an alternative and cost-effective strategy	2009:2050	an alternative and cost-effective strategy to the conventional ERT	2009:2074	Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif.
31842258	8	27	theme	conventional	2059:2070	arg1	ERT					2072:2074	the conventional ERT	2055:2074	the conventional ERT	2055:2074	Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif.
31842258	6	28	theme	IDUA	1483:1486	arg1	efficiency					1431:1440	the efficiency	1427:1440	the efficiency of the purified plant mannose-terminated IDUA	1427:1486	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	7	29	theme	work	1669:1672	arg1	outcome					1654:1660	an exciting outcome	1642:1660	an exciting outcome of our work	1642:1672	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	2	30	theme	cell-based	497:506	arg1	systems					519:525	the commercial mammalian cell-based production systems	472:525	the commercial mammalian cell-based production systems	472:525	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	5	31	theme	recombinant	1239:1249	arg1	enzyme					1261:1266	the endocytosed recombinant lysosomal enzyme	1223:1266	the endocytosed recombinant lysosomal enzyme	1223:1266	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	0	32	theme	Enzyme	77:82	arg1	Therapy					96:102	Enzyme Replacement Therapy	77:102	Enzyme Replacement Therapy of Lysosomal Storage Disorders	77:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	5	33	theme	MPS	1182:1184	arg1	fibroblasts					1196:1206	cultured MPS I primary fibroblasts	1173:1206	cultured MPS I primary fibroblasts	1173:1206	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	4	34	theme	M6P	971:973	arg1	machinery					987:995	the human M6P elaboration machinery	961:995	the human M6P elaboration machinery	961:995	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	2	35	theme	non-immunogenic	654:668	arg1	form					670:673	a biologically active and non-immunogenic form	628:673	a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans	628:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	7	36	theme	exciting	1645:1652	arg1	outcome					1654:1660	an exciting outcome	1642:1660	an exciting outcome of our work	1642:1672	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	0	37	from	Pathway	55:61	arg1	Plants					66:71	Plants	66:71	Plants	66:71	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	2	38	theme	active	643:648	arg1	form					670:673	a biologically active and non-immunogenic form	628:673	a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans	628:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	0	39	theme	Lysosomal	107:115	arg1	Disorders					125:133	Lysosomal Storage Disorders	107:133	Lysosomal Storage Disorders	107:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	7	40	theme	commercial	1779:1788	arg1	IDUA					1790:1793	the commercial IDUA	1775:1793	the commercial IDUA (Aldurazyme® (Sanofi, Paris, France))	1775:1831	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	2	41	theme	safe	452:455	arg1	alternative					457:467	a more cost-effective and safe alternative	426:467	a more cost-effective and safe alternative to the commercial mammalian cell-based production systems	426:525	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	5	42	theme	lysosomal	1251:1259	arg1	enzyme					1261:1266	the endocytosed recombinant lysosomal enzyme	1223:1266	the endocytosed recombinant lysosomal enzyme	1223:1266	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	2	43	theme	high	700:703	arg1	glycans					722:728	predominantly high mannose N-linked glycans	686:728	predominantly high mannose N-linked glycans	686:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	5	44	theme	Uptake	1102:1107	arg1	studies					1109:1115	Uptake studies	1102:1115	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts	1102:1206	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	4	45	theme	single	1073:1078	arg1	construct					1091:1099	a single multi-gene construct	1071:1099	a single multi-gene construct	1071:1099	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	1	46	theme	non-degraded	282:293	arg1	glycosaminoglycans					295:312	non-degraded glycosaminoglycans	282:312	non-degraded glycosaminoglycans in lysosomes	282:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	2	47	theme	commercial	476:485	arg1	systems					519:525	the commercial mammalian cell-based production systems	472:525	the commercial mammalian cell-based production systems	472:525	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	6	48	theme	poor	1502:1505	arg1	M6P-elaboration					1517:1531	a poor in planta M6P-elaboration	1500:1531	a poor in planta M6P-elaboration by the expressed machinery	1500:1558	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	5	49	theme	primary	1188:1194	arg1	fibroblasts					1196:1206	cultured MPS I primary fibroblasts	1173:1206	cultured MPS I primary fibroblasts	1173:1206	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	0	50	theme	6-Phosphate	31:41	arg1	Pathway					55:61	the Mannose 6-Phosphate Elaboration Pathway	19:61	the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders	19:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	7	51	dep	need	1621:1624	arg1	improved					1632:1639	improved	1632:1639	would need to be improved	1615:1639	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	4	52	theme	human	1054:1058	arg1	IDUA					1060:1063	the recombinant human IDUA	1038:1063	the recombinant human IDUA using a single multi-gene construct	1038:1099	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	2	53	from	enzyme	618:623	arg1	form					670:673	a biologically active and non-immunogenic form	628:673	a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans	628:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	54	link	N-linked	713:720	arg1	glycans					722:728	predominantly high mannose N-linked glycans	686:728	predominantly high mannose N-linked glycans	686:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	8	55	theme	M6P	2141:2143	arg1	motif					2145:2149	the M6P motif	2137:2149	the M6P motif	2137:2149	Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif.
31842258	7	56	theme	M6P	1896:1898	arg1	pathway					1921:1927	a M6P receptor-independent pathway	1894:1927	a M6P receptor-independent pathway	1894:1927	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	2	57	theme	replacement	342:352	arg1	therapy					354:360	Costly enzyme replacement therapy	328:360	Costly enzyme replacement therapy (ERT)	328:366	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	57	theme	replacement	342:352	arg1	treatment					388:396	the conventional treatment	371:396	the conventional treatment for MPS I.	371:407	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	57	theme	replacement	342:352	arg1	ERT					363:365	ERT	363:365	ERT	363:365	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	7	58	theme	process	1596:1602	arg1	efficiency					1604:1613	the in planta M6P-tagging process efficiency	1570:1613	the in planta M6P-tagging process efficiency	1570:1613	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	5	59	theme	glycosaminoglycans	1300:1317	arg1	reduction					1287:1295	substantial reduction	1275:1295	substantial reduction of glycosaminoglycans	1275:1317	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	7	60	theme	planta	1577:1582	arg1	efficiency					1604:1613	the in planta M6P-tagging process efficiency	1570:1613	the in planta M6P-tagging process efficiency	1570:1613	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	2	61	from	IDUA	563:566	arg1	seeds					571:575	seeds	571:575	seeds of an Arabidopsis mutant	571:600	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	6	62	theme	mannose-terminated	1464:1481	arg1	IDUA					1483:1486	the purified plant mannose-terminated IDUA	1445:1486	the purified plant mannose-terminated IDUA	1445:1486	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	6	63	theme	M6P-IDUA	1360:1367	arg1	comparable					1411:1420	comparable	1411:1420	comparable	1411:1420	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	6	63	theme	M6P-IDUA	1360:1367	arg1	efficiency					1333:1342	the efficiency	1329:1342	the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage	1329:1405	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	8	64	theme	lysosomal	1974:1982	arg1	hydrolases					1984:1993	lysosomal hydrolases	1974:1993	lysosomal hydrolases	1974:1993	Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif.
31842258	8	65	theme	plant-based	1938:1948	arg1	platform					1950:1957	a plant-based platform	1936:1957	a plant-based platform for generating lysosomal hydrolases	1936:1993	Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif.
31842258	6	66	theme	expressed	1540:1548	arg1	machinery					1550:1558	the expressed machinery	1536:1558	the expressed machinery	1536:1558	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	2	67	theme	mutant	595:600	arg1	seeds					571:575	seeds	571:575	seeds of an Arabidopsis mutant	571:600	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	3	68	from	enzyme	743:748	arg1	ERT					753:755	ERT	753:755	ERT	753:755	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	6	69	theme	plant	1458:1462	arg1	IDUA					1483:1486	the purified plant mannose-terminated IDUA	1445:1486	the purified plant mannose-terminated IDUA	1445:1486	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	1	70	from	accumulation	266:277	arg1	lysosomes					317:325	lysosomes	317:325	lysosomes	317:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	2	71	theme	Costly	328:333	arg1	therapy					354:360	Costly enzyme replacement therapy	328:360	Costly enzyme replacement therapy (ERT)	328:366	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	71	theme	Costly	328:333	arg1	treatment					388:396	the conventional treatment	371:396	the conventional treatment for MPS I.	371:407	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	71	theme	Costly	328:333	arg1	ERT					363:365	ERT	363:365	ERT	363:365	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	1	72	theme	lysosomal	178:186	arg1	I					164:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	1	72	theme	lysosomal	178:186	arg1	disease					196:202	a severe lysosomal storage disease	169:202	a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes	169:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	7	73	theme	comparable	1741:1750	arg1	results					1733:1739	results	1733:1739	results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France))	1733:1831	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	4	74	theme	planta	937:942	arg1	phosphorylation					944:958	planta phosphorylation	937:958	planta phosphorylation	937:958	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	2	75	contain	containing	675:684	arg1	form					670:673	a biologically active and non-immunogenic form	628:673	a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans	628:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	75	contain	containing	675:684	arg2	glycans					722:728	predominantly high mannose N-linked glycans	686:728	predominantly high mannose N-linked glycans	686:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	6	76	from	planta	1510:1515	arg1	poor					1502:1505	poor	1502:1505	poor	1502:1505	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	7	77	theme	mannose-terminated	1701:1718	arg1	IDUA					1720:1723	the plant-derived mannose-terminated IDUA	1683:1723	the plant-derived mannose-terminated IDUA	1683:1723	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	2	78	theme	recombinant	545:555	arg1	IDUA					563:566	recombinant human IDUA	545:566	recombinant human IDUA in seeds of an Arabidopsis mutant	545:600	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	5	79	theme	putative	1132:1139	arg1	M6P-IDUA					1141:1148	purified putative M6P-IDUA	1123:1148	purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts	1123:1206	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	3	80	theme	mannose	791:797	arg1	M6P					812:814	M6P	812:814	M6P	812:814	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	3	80	theme	mannose	791:797	arg1	6-phosphate					799:809	mannose 6-phosphate	791:809	a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome	789:914	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	1	81	theme	Mucopolysaccharidosis	136:156	arg1	I					164:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	1	81	theme	Mucopolysaccharidosis	136:156	arg1	disease					196:202	a severe lysosomal storage disease	169:202	a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes	169:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	3	82	theme	intracellular	877:889	arg1	delivery					891:898	intracellular delivery	877:898	intracellular delivery to the lysosome	877:914	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	6	83	from	poor	1502:1505	arg1	planta					1510:1515	planta	1510:1515	planta	1510:1515	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	1	84	theme	MPS	159:161	arg1	I					164:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I	136:164	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	1	84	theme	MPS	159:161	arg1	disease					196:202	a severe lysosomal storage disease	169:202	a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes	169:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	2	85	theme	production	508:517	arg1	systems					519:525	the commercial mammalian cell-based production systems	472:525	the commercial mammalian cell-based production systems	472:525	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	0	86	theme	Replacement	84:94	arg1	Therapy					96:102	Enzyme Replacement Therapy	77:102	Enzyme Replacement Therapy of Lysosomal Storage Disorders	77:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	5	87	theme	cultured	1173:1180	arg1	fibroblasts					1196:1206	cultured MPS I primary fibroblasts	1173:1206	cultured MPS I primary fibroblasts	1173:1206	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	2	88	theme	mammalian	487:495	arg1	systems					519:525	the commercial mammalian cell-based production systems	472:525	the commercial mammalian cell-based production systems	472:525	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	3	89	theme	patient	855:861	arg1	cells					863:867	patient cells	855:867	patient cells	855:867	Recombinant enzyme in ERT is generally thought to require a mannose 6-phosphate (M6P) targeting signal for endocytosis into patient cells and for intracellular delivery to the lysosome.
31842258	6	90	theme	purified	1449:1456	arg1	IDUA					1483:1486	the purified plant mannose-terminated IDUA	1445:1486	the purified plant mannose-terminated IDUA	1445:1486	However, the efficiency of the putative M6P-IDUA in reducing glycosaminoglycan storage was comparable with the efficiency of the purified plant mannose-terminated IDUA, suggesting a poor in planta M6P-elaboration by the expressed machinery.
31842258	5	91	theme	I	1186:1186	arg1	fibroblasts					1196:1206	cultured MPS I primary fibroblasts	1173:1206	cultured MPS I primary fibroblasts	1173:1206	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	4	92	theme	human	965:969	arg1	machinery					987:995	the human M6P elaboration machinery	961:995	the human M6P elaboration machinery	961:995	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	0	93	theme	Storage	117:123	arg1	Disorders					125:133	Lysosomal Storage Disorders	107:133	Lysosomal Storage Disorders	107:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	4	94	theme	elaboration	975:985	arg1	machinery					987:995	the human M6P elaboration machinery	961:995	the human M6P elaboration machinery	961:995	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	2	95	theme	mannose	705:711	arg1	glycans					722:728	predominantly high mannose N-linked glycans	686:728	predominantly high mannose N-linked glycans	686:728	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	7	96	dep	IDUA	1790:1793	arg1	France					1824:1829	France	1824:1829	France	1824:1829	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	7	96	dep	IDUA	1790:1793	arg1	Aldurazyme®					1796:1806	Aldurazyme®	1796:1806	Aldurazyme®	1796:1806	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	8	97	theme	additional	2105:2114	arg1	processing					2116:2125	additional processing	2105:2125	additional processing	2105:2125	Thus, a plant-based platform for generating lysosomal hydrolases may represent an alternative and cost-effective strategy to the conventional ERT, without the requirement for additional processing to create the M6P motif.
31842258	2	98	theme	conventional	375:386	arg1	therapy					354:360	Costly enzyme replacement therapy	328:360	Costly enzyme replacement therapy (ERT)	328:366	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	98	theme	conventional	375:386	arg1	treatment					388:396	the conventional treatment	371:396	the conventional treatment for MPS I.	371:407	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	0	99	theme	Mannose	23:29	arg1	Pathway					55:61	the Mannose 6-Phosphate Elaboration Pathway	19:61	the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders	19:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	5	100	theme	endocytosed	1227:1237	arg1	enzyme					1261:1266	the endocytosed recombinant lysosomal enzyme	1223:1266	the endocytosed recombinant lysosomal enzyme	1223:1266	Uptake studies using purified putative M6P-IDUA generated in planta on cultured MPS I primary fibroblasts indicated that the endocytosed recombinant lysosomal enzyme led to substantial reduction of glycosaminoglycans.
31842258	0	101	theme	Elaboration	43:53	arg1	Pathway					55:61	the Mannose 6-Phosphate Elaboration Pathway	19:61	the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders	19:133	Toward Engineering the Mannose 6-Phosphate Elaboration Pathway in Plants for Enzyme Replacement Therapy of Lysosomal Storage Disorders.
31842258	1	102	theme	glycosaminoglycans	295:312	arg1	accumulation					266:277	accumulation	266:277	accumulation of non-degraded glycosaminoglycans in lysosomes	266:325	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31842258	4	103	theme	recombinant	1042:1052	arg1	IDUA					1060:1063	the recombinant human IDUA	1038:1063	the recombinant human IDUA using a single multi-gene construct	1038:1099	Toward effecting in planta phosphorylation, the human M6P elaboration machinery was successfully co-expressed along with the recombinant human IDUA using a single multi-gene construct.
31842258	7	104	theme	receptor-independent	1900:1919	arg1	pathway					1921:1927	a M6P receptor-independent pathway	1894:1927	a M6P receptor-independent pathway	1894:1927	Although the in planta M6P-tagging process efficiency would need to be improved, an exciting outcome of our work was that the plant-derived mannose-terminated IDUA yielded results comparable to those obtained with the commercial IDUA (Aldurazyme® (Sanofi, Paris, France)), and a significant amount of the plant-IDUA is trafficked by a M6P receptor-independent pathway.
31842258	2	105	theme	enzyme	335:340	arg1	therapy					354:360	Costly enzyme replacement therapy	328:360	Costly enzyme replacement therapy (ERT)	328:366	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	105	theme	enzyme	335:340	arg1	treatment					388:396	the conventional treatment	371:396	the conventional treatment for MPS I.	371:407	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	2	105	theme	enzyme	335:340	arg1	ERT					363:365	ERT	363:365	ERT	363:365	Costly enzyme replacement therapy (ERT) is the conventional treatment for MPS I. Toward producing a more cost-effective and safe alternative to the commercial mammalian cell-based production systems, we have produced recombinant human IDUA in seeds of an Arabidopsis mutant to generate the enzyme in a biologically active and non-immunogenic form containing predominantly high mannose N-linked glycans.
31842258	1	106	theme	IDUA	231:234	arg1	deficiency					237:246	α-L-iduronidase (IDUA) deficiency	214:246	α-L-iduronidase (IDUA) deficiency	214:246	Mucopolysaccharidosis (MPS) I is a severe lysosomal storage disease caused by α-L-iduronidase (IDUA) deficiency, which results in accumulation of non-degraded glycosaminoglycans in lysosomes.
31094416	2	0	theme	CD146	580:584	arg1	binding					423:429	binding	423:429	binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5)	423:541	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	0	theme	CD146	580:584	arg1	version					569:575	a shorter, D5-deleted version	547:575	a shorter, D5-deleted version of CD146 (D1-D4)	547:592	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	8	1	theme	cell	1775:1778	arg1	receptor					1780:1787	the cell receptor	1771:1787	the cell receptor	1771:1787	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	4	2	theme	canonical	802:810	arg1	β-strands					842:850	β-strands 1, 10, 3, 4, 5, 6	842:868	β-strands	842:850	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	2	theme	canonical	802:810	arg1	S-face					834:839	the canonical sugar-binding β-sheet S-face	798:839	the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich	798:893	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	3	theme	β-sheet	826:832	arg1	β-strands					842:850	β-strands 1, 10, 3, 4, 5, 6	842:868	β-strands	842:850	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	3	theme	β-sheet	826:832	arg1	S-face					834:839	the canonical sugar-binding β-sheet S-face	798:839	the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich	798:893	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	4	with	interactions	910:921	arg1	sites					963:967	N-linked glycosylation sites	940:967	N-linked glycosylation sites	940:967	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	4	with	interactions	910:921	arg1	CD146					928:932	CD146	928:932	CD146	928:932	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	0	5	with	interactions	113:124	arg1	F-face					159:164	the lectin's CRD β-sandwich F-face	131:164	the lectin's CRD β-sandwich F-face	131:164	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	0	6	theme	NMR-based	0:8	arg1	insight					10:16	NMR-based insight	0:16	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.	0:165	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	6	7	theme	Gal-3	1355:1359	arg1	mutants					1368:1374	Gal-3 F-face mutants	1355:1374	Gal-3 F-face mutants	1355:1374	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	6	8	from	increase	1441:1448	arg1	binding					1479:1485	net binding	1475:1485	net binding to CD146 eFL compared to wild type Gal-3	1475:1526	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	5	9	dep	abolish	1305:1311	arg1	attenuating					1228:1238	attenuating	1228:1238	attenuating Gal-3 binding (primarily with the S-face) to CD146 eFL	1228:1293	This is supported by the observation that addition of lactose, while significantly attenuating Gal-3 binding (primarily with the S-face) to CD146 eFL, does not abolish it.
31094416	7	10	theme	lactose	1543:1549	arg1	titrations					1551:1560	HSQC lactose titrations	1538:1560	HSQC lactose titrations	1538:1560	However, HSQC lactose titrations show no highly significant effects on sugar binding to the Gal-3 CRD S-face.
31094416	3	11	from	D5	782:783	arg1	number					749:754	a larger number	740:754	a larger number of glycosylation sites on D5	740:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	4	12	theme	equivalent	971:980	arg1	perturbations					996:1008	equivalent HSQC spectral perturbations	971:1008	equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	971:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	3	13	theme	reduced	684:690	arg1	eFL					708:710	greatly reduced vis-à-vis CD146 eFL	676:710	greatly reduced vis-à-vis CD146 eFL	676:710	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	4	14	gly	glycosylation	949:961	arg2	CD146					928:932	CD146	928:932	CD146	928:932	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	14	gly	glycosylation	949:961	arg2	sites					963:967	N-linked glycosylation sites	940:967	N-linked glycosylation sites	940:967	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	6	15	theme	Bio-Layer	1317:1325	arg1	studies					1342:1348	Bio-Layer Interferometry studies	1317:1348	Bio-Layer Interferometry studies with Gal-3 F-face mutants	1317:1374	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	2	16	theme	ectodomains	524:534	arg1	D1-D5					536:540	five Ig-like ectodomains D1-D5	511:540	five Ig-like ectodomains D1-D5	511:540	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	16	theme	ectodomains	524:534	arg1	CD146					504:508	CD146	504:508	CD146	504:508	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	4	17	theme	spectral	987:994	arg1	perturbations					996:1008	equivalent HSQC spectral perturbations	971:1008	equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	971:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	1	18	theme	adhesion	200:207	arg1	glycoprotein					209:220	cell adhesion glycoprotein CD146	195:226	cell adhesion glycoprotein CD146	195:226	Galectin-3 (Gal-3) binds to cell adhesion glycoprotein CD146 to promote cytokine secretion and mediate endothelial cell migration.
31094416	0	19	theme	CRD	144:146	arg1	F-face					159:164	the lectin's CRD β-sandwich F-face	131:164	the lectin's CRD β-sandwich F-face	131:164	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	5	20	dep	S-face	1274:1279	arg1	primarily					1255:1263	primarily	1255:1263	primarily	1255:1263	This is supported by the observation that addition of lactose, while significantly attenuating Gal-3 binding (primarily with the S-face) to CD146 eFL, does not abolish it.
31094416	3	21	theme	larger	742:747	arg1	number					749:754	a larger number	740:754	a larger number of glycosylation sites on D5	740:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	4	22	theme	opposing	1029:1036	arg1	β-strands					1060:1068	β-strands 11, 2, 7, 8, 9	1060:1083	β-strands	1060:1068	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	22	theme	opposing	1029:1036	arg1	β-sheet					1051:1057	the opposing Gal-3 F-face β-sheet	1025:1057	the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	1025:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	0	23	theme	adhesion	62:69	arg1	molecule					71:78	endothelial cell adhesion molecule CD146	45:84	endothelial cell adhesion molecule CD146	45:84	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	6	24	theme	KD	1382:1383	arg1	values					1385:1390	KD values	1382:1390	KD values	1382:1390	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	4	25	theme	F-face	1044:1049	arg1	β-strands					1060:1068	β-strands 11, 2, 7, 8, 9	1060:1083	β-strands	1060:1068	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	25	theme	F-face	1044:1049	arg1	β-sheet					1051:1057	the opposing Gal-3 F-face β-sheet	1025:1057	the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	1025:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	3	26	theme	sites	773:777	arg1	number					749:754	a larger number	740:754	a larger number of glycosylation sites on D5	740:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	4	27	theme	F-face	1120:1125	arg1	involvement					1095:1105	involvement	1095:1105	involvement of the Gal-3 F-face in binding CD146	1095:1142	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	6	28	theme	wild	1512:1515	arg1	Gal-3					1522:1526	wild type Gal-3	1512:1526	wild type Gal-3	1512:1526	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	8	29	theme	β-galactoside	1745:1757	arg1	epitopes					1759:1766	β-galactoside epitopes	1745:1766	β-galactoside epitopes on the cell receptor	1745:1787	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	2	30	theme	CD146	504:508	arg1	CD146					504:508	CD146	504:508	CD146	504:508	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	30	theme	CD146	504:508	arg1	Gal-3					451:455	15N-labeled Gal-3	439:455	15N-labeled Gal-3	439:455	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	30	theme	CD146	504:508	arg1	eFL					487:489	eFL	487:489	eFL	487:489	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	30	theme	CD146	504:508	arg1	domain					479:484	the extracellular domain	461:484	the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5)	461:541	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	31	theme	HSQC	389:392	arg1	spectroscopy					395:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	0	32	theme	noncanonical	100:111	arg1	interactions					113:124	noncanonical interactions	100:124	noncanonical interactions with the lectin's CRD β-sandwich F-face	100:164	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	7	33	from	effects	1589:1595	arg1	binding					1606:1612	sugar binding	1600:1612	sugar binding to the Gal-3 CRD S-face	1600:1636	However, HSQC lactose titrations show no highly significant effects on sugar binding to the Gal-3 CRD S-face.
31094416	2	34	theme	Coherence	378:386	arg1	spectroscopy					395:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	4	35	dep	Even	786:789	arg1	involved					898:905	involved	898:905	is involved in interactions with CD146 (e.g. N-linked glycosylation sites)	895:968	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	1	36	theme	endothelial	270:280	arg1	migration					287:295	endothelial cell migration	270:295	endothelial cell migration	270:295	Galectin-3 (Gal-3) binds to cell adhesion glycoprotein CD146 to promote cytokine secretion and mediate endothelial cell migration.
31094416	4	37	dep	sites	963:967	arg1	e.g.					935:938	e.g.	935:938	e.g.	935:938	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	38	theme	Gal-3	878:882	arg1	β-sandwich					884:893	the Gal-3 β-sandwich	874:893	the Gal-3 β-sandwich	874:893	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	3	39	from	sites	773:777	arg1	D5					782:783	D5	782:783	D5	782:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	4	40	theme	Gal-3	1114:1118	arg1	F-face					1120:1125	the Gal-3 F-face	1110:1125	the Gal-3 F-face	1110:1125	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	8	41	theme	CRD	1839:1841	arg1	F-face					1843:1848	the lectin's CRD F-face	1826:1848	the lectin's CRD F-face	1826:1848	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	0	42	theme	endothelial	45:55	arg1	molecule					71:78	endothelial cell adhesion molecule CD146	45:84	endothelial cell adhesion molecule CD146	45:84	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	8	43	from	role	1817:1820	arg1	process					1871:1877	the CD146 binding process	1853:1877	the CD146 binding process	1853:1877	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	4	44	from	involvement	1095:1105	arg1	binding					1130:1136	binding CD146	1130:1142	binding CD146	1130:1142	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	45	link	N-linked	940:947	arg1	sites					963:967	N-linked glycosylation sites	940:967	N-linked glycosylation sites	940:967	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	45	link	N-linked	940:947	arg1	CD146					928:932	CD146	928:932	CD146	928:932	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	2	46	theme	Magnetic	320:327	arg1	Resonance					329:337	Nuclear Magnetic Resonance	312:337	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	46	theme	Magnetic	320:327	arg1	NMR					340:342	NMR	340:342	NMR	340:342	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	3	47	theme	carbohydrate	620:631	arg1	CRD					653:655	CRD	653:655	CRD	653:655	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	3	47	theme	carbohydrate	620:631	arg1	domain					645:650	its carbohydrate recognition domain	616:650	its carbohydrate recognition domain (CRD)	616:656	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	2	48	theme	Single	363:368	arg1	spectroscopy					395:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	7	49	theme	significant	1577:1587	arg1	effects					1589:1595	no highly significant effects	1567:1595	no highly significant effects on sugar binding to the Gal-3 CRD S-face	1567:1636	However, HSQC lactose titrations show no highly significant effects on sugar binding to the Gal-3 CRD S-face.
31094416	5	50	theme	lactose	1199:1205	arg1	addition					1187:1194	addition	1187:1194	addition of lactose	1187:1205	This is supported by the observation that addition of lactose, while significantly attenuating Gal-3 binding (primarily with the S-face) to CD146 eFL, does not abolish it.
31094416	1	51	theme	cytokine	239:246	arg1	secretion					248:256	cytokine secretion	239:256	cytokine secretion	239:256	Galectin-3 (Gal-3) binds to cell adhesion glycoprotein CD146 to promote cytokine secretion and mediate endothelial cell migration.
31094416	2	52	dep	shorter	549:555	arg1	D5-deleted					558:567	D5-deleted	558:567	D5-deleted	558:567	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	4	53	theme	N-linked	940:947	arg1	sites					963:967	N-linked glycosylation sites	940:967	N-linked glycosylation sites	940:967	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	53	theme	N-linked	940:947	arg1	CD146					928:932	CD146	928:932	CD146	928:932	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	8	54	with	interactions	1727:1738	arg1	epitopes					1759:1766	β-galactoside epitopes	1745:1766	β-galactoside epitopes on the cell receptor	1745:1787	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	4	55	theme	sugar-binding	812:824	arg1	β-strands					842:850	β-strands 1, 10, 3, 4, 5, 6	842:868	β-strands	842:850	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	55	theme	sugar-binding	812:824	arg1	S-face					834:839	the canonical sugar-binding β-sheet S-face	798:839	the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich	798:893	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	6	56	theme	F-face	1361:1366	arg1	mutants					1368:1374	Gal-3 F-face mutants	1355:1374	Gal-3 F-face mutants	1355:1374	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	7	57	theme	HSQC	1538:1541	arg1	titrations					1551:1560	HSQC lactose titrations	1538:1560	HSQC lactose titrations	1538:1560	However, HSQC lactose titrations show no highly significant effects on sugar binding to the Gal-3 CRD S-face.
31094416	4	58	from	residues	1013:1020	arg1	β-sheet					1051:1057	the opposing Gal-3 F-face β-sheet	1025:1057	the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	1025:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	58	from	residues	1013:1020	arg1	β-strands					1060:1068	β-strands 11, 2, 7, 8, 9	1060:1083	β-strands	1060:1068	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	58	from	residues	1013:1020	arg1	perturbations					996:1008	equivalent HSQC spectral perturbations	971:1008	equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	971:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	59	theme	HSQC	982:985	arg1	perturbations					996:1008	equivalent HSQC spectral perturbations	971:1008	equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	971:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	8	60	theme	Gal-3	1675:1679	arg1	binding					1681:1687	Gal-3 binding	1675:1687	Gal-3 binding to CD146	1675:1696	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	6	61	theme	Interferometry	1327:1340	arg1	studies					1342:1348	Bio-Layer Interferometry studies	1317:1348	Bio-Layer Interferometry studies with Gal-3 F-face mutants	1317:1374	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	3	62	theme	vis-à-vis	692:700	arg1	eFL					708:710	greatly reduced vis-à-vis CD146 eFL	676:710	greatly reduced vis-à-vis CD146 eFL	676:710	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	1	63	theme	cell	195:198	arg1	glycoprotein					209:220	cell adhesion glycoprotein CD146	195:226	cell adhesion glycoprotein CD146	195:226	Galectin-3 (Gal-3) binds to cell adhesion glycoprotein CD146 to promote cytokine secretion and mediate endothelial cell migration.
31094416	2	64	theme	Ig-like	516:522	arg1	ectodomains					524:534	five Ig-like ectodomains	511:534	five Ig-like ectodomains D1-D5	511:540	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	6	65	theme	net	1475:1477	arg1	binding					1479:1485	net binding	1475:1485	net binding to CD146 eFL compared to wild type Gal-3	1475:1526	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	0	66	theme	β-sandwich	148:157	arg1	F-face					159:164	the lectin's CRD β-sandwich F-face	131:164	the lectin's CRD β-sandwich F-face	131:164	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	6	67	theme	significant	1409:1419	arg1	L203A					1431:1435	L203A	1431:1435	L203A	1431:1435	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	6	67	theme	significant	1409:1419	arg1	decrease					1421:1428	a significant decrease	1407:1428	a significant decrease (L203A)	1407:1436	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	2	68	theme	shorter	549:555	arg1	version					569:575	a shorter, D5-deleted version	547:575	a shorter, D5-deleted version of CD146 (D1-D4)	547:592	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	3	69	theme	domain	645:650	arg1	Binding					595:601	Binding	595:601	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4	595:671	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	6	70	with	studies	1342:1348	arg1	mutants					1368:1374	Gal-3 F-face mutants	1355:1374	Gal-3 F-face mutants	1355:1374	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	6	71	from	decrease	1421:1428	arg1	binding					1479:1485	net binding	1475:1485	net binding to CD146 eFL compared to wild type Gal-3	1475:1526	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	8	72	theme	direct	1810:1815	arg1	role					1817:1820	a direct role	1808:1820	a direct role for the lectin's CRD F-face in the CD146 binding process	1808:1877	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	8	73	from	epitopes	1759:1766	arg1	receptor					1780:1787	the cell receptor	1771:1787	the cell receptor	1771:1787	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	4	74	theme	Gal-3	1038:1042	arg1	β-strands					1060:1068	β-strands 11, 2, 7, 8, 9	1060:1083	β-strands	1060:1068	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	74	theme	Gal-3	1038:1042	arg1	β-sheet					1051:1057	the opposing Gal-3 F-face β-sheet	1025:1057	the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9)	1025:1084	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	3	75	theme	number	749:754	arg1	proposal					728:735	the proposal	724:735	the proposal of a larger number of glycosylation sites on D5	724:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	8	76	theme	simple	1720:1725	arg1	interactions					1727:1738	simple interactions	1720:1738	simple interactions with β-galactoside epitopes on the cell receptor	1720:1787	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	2	77	theme	Resonance	329:337	arg1	spectroscopy					395:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	3	78	from	number	749:754	arg1	D5					782:783	D5	782:783	D5	782:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	6	79	theme	type	1517:1520	arg1	Gal-3					1522:1526	wild type Gal-3	1512:1526	wild type Gal-3	1512:1526	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	1	80	gly	glycoprotein	209:220	arg1	glycoprotein					209:220	cell adhesion glycoprotein CD146	195:226	cell adhesion glycoprotein CD146	195:226	Galectin-3 (Gal-3) binds to cell adhesion glycoprotein CD146 to promote cytokine secretion and mediate endothelial cell migration.
31094416	3	81	theme	glycosylation	759:771	arg1	sites					773:777	glycosylation sites	759:777	glycosylation sites on D5	759:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	2	82	theme	15N-labeled	439:449	arg1	Gal-3					451:455	15N-labeled Gal-3	439:455	15N-labeled Gal-3	439:455	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	83	theme	Quantum	370:376	arg1	spectroscopy					395:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	1	84	theme	cell	282:285	arg1	migration					287:295	endothelial cell migration	270:295	endothelial cell migration	270:295	Galectin-3 (Gal-3) binds to cell adhesion glycoprotein CD146 to promote cytokine secretion and mediate endothelial cell migration.
31094416	2	85	dep	CD146	504:508	arg1	purified					495:502	purified	495:502	purified	495:502	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	6	86	dep	increase	1441:1448	arg1	T243A					1465:1469	T243A	1465:1469	T243A	1465:1469	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	6	86	dep	increase	1441:1448	arg1	L218A					1458:1462	L218A	1458:1462	L218A	1458:1462	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	6	86	dep	increase	1441:1448	arg1	V204A					1451:1455	V204A	1451:1455	V204A	1451:1455	Bio-Layer Interferometry studies with Gal-3 F-face mutants yield KD values to demonstrate a significant decrease (L203A) or increase (V204A, L218A, T243A) in net binding to CD146 eFL compared to wild type Gal-3.
31094416	3	87	theme	Gal-3	606:610	arg1	Binding					595:601	Binding	595:601	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4	595:671	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	5	88	with	binding	1246:1252	arg1	S-face					1274:1279	the S-face	1270:1279	the S-face	1270:1279	This is supported by the observation that addition of lactose, while significantly attenuating Gal-3 binding (primarily with the S-face) to CD146 eFL, does not abolish it.
31094416	2	89	theme	extracellular	465:477	arg1	CD146					504:508	CD146	504:508	CD146	504:508	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	89	theme	extracellular	465:477	arg1	eFL					487:489	eFL	487:489	eFL	487:489	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	89	theme	extracellular	465:477	arg1	domain					479:484	the extracellular domain	461:484	the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5)	461:541	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	0	90	theme	cell	57:60	arg1	molecule					71:78	endothelial cell adhesion molecule CD146	45:84	endothelial cell adhesion molecule CD146	45:84	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	7	91	theme	Gal-3	1621:1625	arg1	S-face					1631:1636	the Gal-3 CRD S-face	1617:1636	the Gal-3 CRD S-face	1617:1636	However, HSQC lactose titrations show no highly significant effects on sugar binding to the Gal-3 CRD S-face.
31094416	4	92	theme	β-sandwich	884:893	arg1	β-strands					842:850	β-strands 1, 10, 3, 4, 5, 6	842:868	β-strands	842:850	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	92	theme	β-sandwich	884:893	arg1	S-face					834:839	the canonical sugar-binding β-sheet S-face	798:839	the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich	798:893	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	3	93	theme	recognition	633:643	arg1	CRD					653:655	CRD	653:655	CRD	653:655	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	3	93	theme	recognition	633:643	arg1	domain					645:650	its carbohydrate recognition domain	616:650	its carbohydrate recognition domain (CRD)	616:656	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	3	94	gly	glycosylation	759:771	arg2	sites					773:777	glycosylation sites	759:777	glycosylation sites on D5	759:783	Binding of Gal-3 and its carbohydrate recognition domain (CRD) to CD146 D1-D4 is greatly reduced vis-à-vis CD146 eFL, supporting the proposal of a larger number of glycosylation sites on D5.
31094416	7	95	theme	CRD	1627:1629	arg1	S-face					1631:1636	the Gal-3 CRD S-face	1617:1636	the Gal-3 CRD S-face	1617:1636	However, HSQC lactose titrations show no highly significant effects on sugar binding to the Gal-3 CRD S-face.
31094416	8	96	theme	binding	1863:1869	arg1	process					1871:1877	the CD146 binding process	1853:1877	the CD146 binding process	1853:1877	Overall, our findings indicate that Gal-3 binding to CD146 is more involved than simple interactions with β-galactoside epitopes on the cell receptor, and that there is a direct role for the lectin's CRD F-face in the CD146 binding process.
31094416	4	97	theme	glycosylation	949:961	arg1	sites					963:967	N-linked glycosylation sites	940:967	N-linked glycosylation sites	940:967	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	4	97	theme	glycosylation	949:961	arg1	CD146					928:932	CD146	928:932	CD146	928:932	Even though the canonical sugar-binding β-sheet S-face (β-strands 1, 10, 3, 4, 5, 6) of the Gal-3 β-sandwich is involved in interactions with CD146 (e.g. N-linked glycosylation sites), equivalent HSQC spectral perturbations at residues on the opposing Gal-3 F-face β-sheet (β-strands 11, 2, 7, 8, 9) indicate involvement of the Gal-3 F-face in binding CD146.
31094416	5	98	theme	Gal-3	1240:1244	arg1	binding					1246:1252	Gal-3 binding	1240:1252	Gal-3 binding (primarily with the S-face) to CD146 eFL	1240:1293	This is supported by the observation that addition of lactose, while significantly attenuating Gal-3 binding (primarily with the S-face) to CD146 eFL, does not abolish it.
31094416	2	99	theme	Nuclear	312:318	arg1	Resonance					329:337	Nuclear Magnetic Resonance	312:337	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	99	theme	Nuclear	312:318	arg1	NMR					340:342	NMR	340:342	NMR	340:342	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	0	100	dep	insight	10:16	arg1	Evidence					87:94	Evidence	87:94	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.	0:165	NMR-based insight into galectin-3 binding to endothelial cell adhesion molecule CD146: Evidence for noncanonical interactions with the lectin's CRD β-sandwich F-face.
31094416	7	101	theme	sugar	1600:1604	arg1	binding					1606:1612	sugar binding	1600:1612	sugar binding to the Gal-3 CRD S-face	1600:1636	However, HSQC lactose titrations show no highly significant effects on sugar binding to the Gal-3 CRD S-face.
31094416	2	102	used	used	307:310	arg2	we					304:305	we	304:305	we	304:305	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
31094416	2	103	theme	15N-Heteronuclear	345:361	arg1	spectroscopy					395:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy	312:406	Here, we used Nuclear Magnetic Resonance (NMR) 15N-Heteronuclear Single Quantum Coherence (HSQC) spectroscopy to investigate binding between 15N-labeled Gal-3 and the extracellular domain (eFL) of purified CD146 (five Ig-like ectodomains D1-D5) and a shorter, D5-deleted version of CD146 (D1-D4).
30529011	8	0	theme	DKO	1025:1027	arg1	mice					1029:1032	DKO mice	1025:1032	DKO mice	1025:1032	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	10	1	theme	cortical	1395:1402	arg1	porosity					1404:1411	high cortical porosity	1390:1411	high cortical porosity in DKO mice	1390:1423	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	9	2	theme	long	1268:1271	arg1	bones					1273:1277	DKO long bones	1264:1277	DKO long bones	1264:1277	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	7	3	theme	Rich	993:996	arg1	MEPE					998:1001	Acidic Serine-Aspartate Rich MEPE	969:1001	Acidic Serine-Aspartate Rich MEPE associated	969:1012	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	7	3	theme	Rich	993:996	arg1	ASARM					962:966	its ASARM	958:966	its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides	958:1022	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	4	4	theme	phenotype	574:582	arg1	understanding					551:563	the understanding	547:563	the understanding of their phenotype	547:582	However, OPN is overexpressed in BSP-/- mice, complicating the understanding of their phenotype.
30529011	1	5	theme	Binding	145:151	arg1	Glycoproteins					169:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	8	6	theme	active	1059:1064	arg1	formation					1066:1074	active formation	1059:1074	active formation of trabecular, secondary bone as well as primary bone	1059:1128	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	8	7	theme	primary	1117:1123	arg1	bone					1125:1128	primary bone	1117:1128	trabecular, secondary bone as well as primary bone	1079:1128	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	7	8	theme	ASARM	962:966	arg1	peptides					1015:1022	its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides	958:1022	its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides	958:1022	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	1	9	theme	N-linked	160:167	arg1	Glycoproteins					169:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	2	10	theme	bone	321:324	arg1	formation					326:334	bone formation	321:334	bone formation	321:334	In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired.
30529011	10	11	theme	bone	1443:1446	arg1	modeling/remodeling					1448:1466	an active bone modeling/remodeling	1433:1466	an active bone modeling/remodeling	1433:1466	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	0	12	theme	bone	98:101	arg1	turnover					103:110	high bone turnover	93:110	high bone turnover	93:110	Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover.
30529011	3	13	theme	mineralization	472:485	arg1	inhibitor					459:467	an inhibitor	456:467	an inhibitor of mineralization	456:485	OPN-/- mice display impaired resorption, and OPN is described as an inhibitor of mineralization.
30529011	3	13	theme	mineralization	472:485	arg1	OPN					436:438	OPN	436:438	OPN	436:438	OPN-/- mice display impaired resorption, and OPN is described as an inhibitor of mineralization.
30529011	10	14	theme	key	1491:1493	arg1	regulators					1495:1504	two key regulators	1487:1504	two key regulators of bone cell performance	1487:1529	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	8	15	theme	marrow-ablation	1137:1151	arg1	model					1160:1164	the marrow-ablation repair model	1133:1164	the marrow-ablation repair model	1133:1164	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	11	16	theme	KO	1679:1680	arg1	interpretation					1649:1662	the interpretation	1645:1662	the interpretation of each single KO	1645:1680	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	5	17	theme	double	633:638	arg1	DKO					644:646	DKO	644:646	DKO	644:646	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	5	17	theme	double	633:638	arg1	KO					640:641	a double KO	631:641	a double KO (DKO) of OPN and BSP	631:662	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	11	18	dep	singular	1591:1598	arg1	non-trivial					1601:1611	non-trivial	1601:1611	non-trivial	1601:1611	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	1	19	theme	bone	185:188	arg1	BSP					204:206	BSP	204:206	BSP	204:206	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	1	19	theme	bone	185:188	arg1	sialoprotein					190:201	bone sialoprotein	185:201	bone sialoprotein (BSP)	185:207	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	8	20	theme	bone	1101:1104	arg1	formation					1066:1074	active formation	1059:1074	active formation of trabecular, secondary bone as well as primary bone	1059:1128	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	10	21	from	porosity	1404:1411	arg1	mice					1420:1423	DKO mice	1416:1423	DKO mice	1416:1423	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	11	22	theme	singular	1591:1598	arg1	phenotype					1613:1621	a singular, non-trivial phenotype	1589:1621	a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO	1589:1680	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	5	23	theme	OPN	652:654	arg1	DKO					644:646	DKO	644:646	DKO	644:646	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	5	23	theme	OPN	652:654	arg1	KO					640:641	a double KO	631:641	a double KO (DKO) of OPN and BSP	631:662	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	0	24	theme	bone	54:57	arg1	hypomineralization					59:76	bone hypomineralization	54:76	bone hypomineralization	54:76	Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover.
30529011	1	25	theme	Small	130:134	arg1	Glycoproteins					169:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	10	26	from	parameters	1374:1383	arg1	mice					1420:1423	DKO mice	1416:1423	DKO mice	1416:1423	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	0	27	from	Deletion	0:7	arg1	mice					32:35	BSP knockout mice	19:35	BSP knockout mice	19:35	Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover.
30529011	9	28	theme	higher	1169:1174	arg1	number					1176:1181	A higher number	1167:1181	A higher number of osteoclasts	1167:1196	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	7	29	theme	ASARM	840:844	arg1	motif					846:850	ASARM motif	840:850	ASARM motif (MEPE)	840:857	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	7	29	theme	ASARM	840:844	arg1	MEPE					853:856	MEPE	853:856	MEPE	853:856	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	10	30	theme	High	1339:1342	arg1	formation					1349:1357	High bone formation	1339:1357	High bone formation	1339:1357	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	10	31	theme	bone	1509:1512	arg1	performance					1519:1529	bone cell performance	1509:1529	bone cell performance	1509:1529	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	10	32	theme	regulators	1495:1504	arg1	absence					1476:1482	the absence	1472:1482	the absence of two key regulators of bone cell performance	1472:1529	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	7	33	theme	matrix	794:799	arg1	phosphoglycoprotein					815:833	The SIBLING, matrix extracellular phosphoglycoprotein	781:833	phosphoglycoprotein	815:833	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	10	34	theme	resorption	1363:1372	arg1	parameters					1374:1383	High bone formation and resorption parameters	1339:1383	High bone formation and resorption parameters	1339:1383	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	0	35	theme	OPN	12:14	arg1	Deletion					0:7	Deletion	0:7	Deletion of OPN in BSP knockout mice	0:35	Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover.
30529011	9	36	theme	DKO	1206:1208	arg1	cultures					1217:1224	DKO marrow cultures	1206:1224	DKO marrow cultures	1206:1224	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	6	37	theme	DKO	744:746	arg1	bones					748:752	DKO bones	744:752	DKO bones	744:752	Despite the absence of OPN, DKO bones are still hypomineralized.
30529011	10	38	theme	formation	1349:1357	arg1	parameters					1374:1383	High bone formation and resorption parameters	1339:1383	High bone formation and resorption parameters	1339:1383	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	10	39	theme	performance	1519:1529	arg1	regulators					1495:1504	two key regulators	1487:1504	two key regulators of bone cell performance	1487:1529	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	0	40	theme	BSP	19:21	arg1	mice					32:35	BSP knockout mice	19:35	BSP knockout mice	19:35	Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover.
30529011	6	41	theme	OPN	739:741	arg1	absence					728:734	the absence	724:734	the absence of OPN	724:741	Despite the absence of OPN, DKO bones are still hypomineralized.
30529011	10	42	theme	high	1390:1393	arg1	porosity					1404:1411	high cortical porosity	1390:1411	high cortical porosity in DKO mice	1390:1423	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	11	43	theme	double	1543:1548	arg1	KO					1550:1551	This first double KO	1532:1551	This first double KO of SIBLING proteins	1532:1571	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	3	44	theme	impaired	411:418	arg1	resorption					420:429	impaired resorption	411:429	impaired resorption	411:429	OPN-/- mice display impaired resorption, and OPN is described as an inhibitor of mineralization.
30529011	10	45	theme	bone	1344:1347	arg1	formation					1349:1357	High bone formation	1339:1357	High bone formation	1339:1357	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	2	46	theme	mature	280:285	arg1	mice					310:313	mature BSP knockout (KO, -/-) mice	280:313	mice	310:313	In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired.
30529011	9	47	theme	resorption	1239:1248	arg1	activity					1250:1257	higher resorption activity	1232:1257	higher resorption activity	1232:1257	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	7	48	gly	phosphoglycoprotein	815:833	arg1	phosphoglycoprotein					815:833	The SIBLING, matrix extracellular phosphoglycoprotein	781:833	phosphoglycoprotein	815:833	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	10	49	theme	DKO	1416:1418	arg1	mice					1420:1423	DKO mice	1416:1423	DKO mice	1416:1423	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	11	50	theme	proteins	1564:1571	arg1	KO					1550:1551	This first double KO	1532:1551	This first double KO of SIBLING proteins	1532:1571	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	2	51	theme	-/-	305:307	arg1	mice					310:313	mature BSP knockout (KO, -/-) mice	280:313	mice	310:313	In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired.
30529011	9	52	theme	localized	1289:1297	arg1	macroporosity					1324:1336	a localized and conspicuous cortical macroporosity	1287:1336	a localized and conspicuous cortical macroporosity	1287:1336	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	2	53	theme	KO	301:302	arg1	mice					310:313	mature BSP knockout (KO, -/-) mice	280:313	mice	310:313	In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired.
30529011	9	54	theme	DKO	1264:1266	arg1	bones					1273:1277	DKO long bones	1264:1277	DKO long bones	1264:1277	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	10	55	theme	active	1436:1441	arg1	modeling/remodeling					1448:1466	an active bone modeling/remodeling	1433:1466	an active bone modeling/remodeling	1433:1466	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	2	56	theme	knockout	291:298	arg1	mice					310:313	mature BSP knockout (KO, -/-) mice	280:313	mice	310:313	In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired.
30529011	1	57	theme	Integrin	136:143	arg1	Glycoproteins					169:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	7	58	theme	peptides	1015:1022	arg1	liberation					944:953	liberation	944:953	liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides	944:1022	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	5	59	theme	BSP	660:662	arg1	DKO					644:646	DKO	644:646	DKO	644:646	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	5	59	theme	BSP	660:662	arg1	KO					640:641	a double KO	631:641	a double KO (DKO) of OPN and BSP	631:662	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	1	60	theme	Ligand	153:158	arg1	Glycoproteins					169:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	9	61	theme	cortical	1315:1322	arg1	macroporosity					1324:1336	a localized and conspicuous cortical macroporosity	1287:1336	a localized and conspicuous cortical macroporosity	1287:1336	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	8	62	theme	formation	1066:1074	arg1	evidence					1047:1054	evidence	1047:1054	evidence of active formation of trabecular, secondary bone as well as primary bone	1047:1128	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	7	63	with	phosphoglycoprotein	815:833	arg1	motif					846:850	ASARM motif	840:850	ASARM motif (MEPE)	840:857	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	7	63	with	phosphoglycoprotein	815:833	arg1	MEPE					853:856	MEPE	853:856	MEPE	853:856	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	8	64	theme	bone	1125:1128	arg1	formation					1066:1074	active formation	1059:1074	active formation of trabecular, secondary bone as well as primary bone	1059:1128	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	2	65	theme	BSP	287:289	arg1	mice					310:313	mature BSP knockout (KO, -/-) mice	280:313	mice	310:313	In mature BSP knockout (KO, -/-) mice, both bone formation and resorption as well as mineralization are impaired.
30529011	11	66	theme	particular	1697:1706	arg1	mineralization					1715:1728	particular matrix mineralization	1697:1728	particular matrix mineralization	1697:1728	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	9	67	theme	conspicuous	1303:1313	arg1	macroporosity					1324:1336	a localized and conspicuous cortical macroporosity	1287:1336	a localized and conspicuous cortical macroporosity	1287:1336	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	8	68	theme	trabecular	1079:1088	arg1	bone					1101:1104	trabecular, secondary bone	1079:1104	trabecular, secondary bone as well as primary bone	1079:1128	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	8	69	theme	repair	1153:1158	arg1	model					1160:1164	the marrow-ablation repair model	1133:1164	the marrow-ablation repair model	1133:1164	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	11	70	theme	single	1672:1677	arg1	KO					1679:1680	each single KO	1667:1680	each single KO	1667:1680	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	0	71	theme	high	93:96	arg1	turnover					103:110	high bone turnover	93:110	high bone turnover	93:110	Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover.
30529011	1	72	link	N-linked	160:167	arg1	Glycoproteins					169:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	11	73	theme	activity	1762:1769	arg1	mineralization					1715:1728	particular matrix mineralization	1697:1728	particular matrix mineralization	1697:1728	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	11	73	theme	activity	1762:1769	arg1	regulation					1738:1747	the regulation	1734:1747	the regulation of bone cell activity	1734:1769	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	9	74	theme	osteoclasts	1186:1196	arg1	number					1176:1181	A higher number	1167:1181	A higher number of osteoclasts	1167:1196	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	11	75	theme	bone	1752:1755	arg1	activity					1762:1769	bone cell activity	1752:1769	bone cell activity	1752:1769	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	5	76	theme	respective	690:699	arg1	contributions					701:713	their respective contributions	684:713	their respective contributions	684:713	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	7	77	theme	extracellular	801:813	arg1	phosphoglycoprotein					815:833	The SIBLING, matrix extracellular phosphoglycoprotein	781:833	phosphoglycoprotein	815:833	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	1	78	dep	SIBLING	121:127	arg1	Glycoproteins					169:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	Small Integrin Binding Ligand N-linked Glycoproteins	130:181	The two SIBLING (Small Integrin Binding Ligand N-linked Glycoproteins), bone sialoprotein (BSP) and osteopontin (OPN) are expressed in osteoblasts and osteoclasts.
30529011	3	79	theme	OPN-/-	391:396	arg1	mice					398:401	OPN-/- mice	391:401	OPN-/- mice	391:401	OPN-/- mice display impaired resorption, and OPN is described as an inhibitor of mineralization.
30529011	0	80	theme	knockout	23:30	arg1	mice					32:35	BSP knockout mice	19:35	BSP knockout mice	19:35	Deletion of OPN in BSP knockout mice does not correct bone hypomineralization but results in high bone turnover.
30529011	9	81	theme	marrow	1210:1215	arg1	cultures					1217:1224	DKO marrow cultures	1206:1224	DKO marrow cultures	1206:1224	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	5	82	with	mice	621:624	arg1	DKO					644:646	DKO	644:646	DKO	644:646	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	5	82	with	mice	621:624	arg1	KO					640:641	a double KO	631:641	a double KO (DKO) of OPN and BSP	631:662	We have generated and characterized mice with a double KO (DKO) of OPN and BSP, to try and unravel their respective contributions.
30529011	11	83	theme	cell	1757:1760	arg1	activity					1762:1769	bone cell activity	1752:1769	bone cell activity	1752:1769	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	8	84	dep	trabecular	1079:1088	arg1	secondary					1091:1099	secondary	1091:1099	secondary	1091:1099	DKO mice also display evidence of active formation of trabecular, secondary bone as well as primary bone in the marrow-ablation repair model.
30529011	11	85	theme	first	1537:1541	arg1	KO					1550:1551	This first double KO	1532:1551	This first double KO of SIBLING proteins	1532:1571	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	10	86	theme	cell	1514:1517	arg1	performance					1519:1529	bone cell performance	1509:1529	bone cell performance	1509:1529	High bone formation and resorption parameters, and high cortical porosity in DKO mice suggest an active bone modeling/remodeling, in the absence of two key regulators of bone cell performance.
30529011	11	87	theme	matrix	1708:1713	arg1	mineralization					1715:1728	particular matrix mineralization	1697:1728	particular matrix mineralization	1697:1728	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30529011	7	88	theme	SIBLING	785:791	arg1	phosphoglycoprotein					815:833	The SIBLING, matrix extracellular phosphoglycoprotein	781:833	phosphoglycoprotein	815:833	The SIBLING, matrix extracellular phosphoglycoprotein with ASARM motif (MEPE) is highly overexpressed in both BSP-/- and DKO and may impair mineralization through liberation of its ASARM (Acidic Serine-Aspartate Rich MEPE associated) peptides.
30529011	9	89	theme	higher	1232:1237	arg1	activity					1250:1257	higher resorption activity	1232:1257	higher resorption activity	1232:1257	A higher number of osteoclasts form in DKO marrow cultures, with higher resorption activity, and DKO long bones display a localized and conspicuous cortical macroporosity.
30529011	4	90	theme	BSP-/-	521:526	arg1	mice					528:531	BSP-/- mice	521:531	BSP-/- mice	521:531	However, OPN is overexpressed in BSP-/- mice, complicating the understanding of their phenotype.
30529011	11	91	theme	SIBLING	1556:1562	arg1	proteins					1564:1571	SIBLING proteins	1556:1571	SIBLING proteins	1556:1571	This first double KO of SIBLING proteins thus results in a singular, non-trivial phenotype leading to reconsider the interpretation of each single KO, concerning in particular matrix mineralization and the regulation of bone cell activity.
30214607	5	0	dep	h.	968:969	arg1	determined					1004:1013	determined	1004:1013	was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction	1000:1291	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	9	1	theme	improved	2017:2024	arg1	approach					2026:2033	an improved approach	2014:2033	an improved approach to target the stemness of CSCs	2014:2064	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	9	1	theme	improved	2017:2024	arg1	treatment					1997:2005	glucosamine treatment	1985:2005	glucosamine treatment	1985:2005	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	1	2	theme	various	236:242	arg1	effects					255:261	various anticancer effects	236:261	various anticancer effects	236:261	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	4	3	theme	study	639:643	arg1	aim					620:622	The aim	616:622	The aim of the present study	616:643	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	8	4	theme	decreased	1762:1770	arg1	number					1772:1777	a decreased number	1760:1777	a decreased number of MFUs	1760:1785	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	5	5	theme	phosphorylated	1308:1321	arg1	pSTAT3					1330:1335	pSTAT3	1330:1335	pSTAT3	1330:1335	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	5	theme	phosphorylated	1308:1321	arg1	STAT3					1323:1327	phosphorylated STAT3	1308:1327	phosphorylated STAT3 (pSTAT3)	1308:1336	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	2	6	theme	improved	412:419	arg1	strategy					347:354	an alternative strategy	332:354	an alternative strategy that targets post-translational glycosylation	332:400	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	2	6	theme	improved	412:419	arg1	approach					421:428	an improved approach	409:428	an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs	409:526	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	1	7	theme	cancer	146:151	arg1	cells					153:157	cancer cells	146:157	cancer cells	146:157	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	1	8	theme	anticancer	244:253	arg1	effects					255:261	various anticancer effects	236:261	various anticancer effects	236:261	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	6	9	theme	mammosphere-forming	1425:1443	arg1	MFUs					1452:1455	MFUs	1452:1455	MFUs	1452:1455	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	6	9	theme	mammosphere-forming	1425:1443	arg1	units					1445:1449	mammosphere-forming units	1425:1449	mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells	1425:1492	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	1	10	theme	responsible	159:169	arg1	cells					110:114	Cancer stem cells	98:114	Cancer stem cells (CSCs)	98:121	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	1	10	theme	responsible	159:169	arg1	subpopulation					129:141	a subpopulation	127:141	a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects	127:261	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	6	11	theme	MCF7	1483:1486	arg1	cells					1488:1492	MCF7 cells	1483:1492	MCF7 cells	1483:1492	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	8	12	theme	ALDH+	1654:1658	arg1	CSCs					1667:1670	ALDH+ breast CSCs	1654:1670	ALDH+ breast CSCs	1654:1670	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	1	13	theme	tumor	175:179	arg1	maintenance					181:191	tumor maintenance	175:191	tumor maintenance	175:191	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	8	14	theme	CSCs	1667:1670	arg1	stemness					1642:1649	the stemness	1638:1649	the stemness of ALDH+ breast CSCs and MCF7 cells	1638:1685	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	8	15	theme	MCF7	1676:1679	arg1	cells					1681:1685	MCF7 cells	1676:1685	MCF7 cells	1676:1685	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	5	16	theme	MCF7	876:879	arg1	cells					881:885	MCF7 cells	876:885	MCF7 cells	876:885	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	9	17	theme	pSTAT3/STAT3	1850:1861	arg1	ratio					1863:1867	a decreased pSTAT3/STAT3 ratio	1838:1867	a decreased pSTAT3/STAT3 ratio	1838:1867	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	6	18	from	cells	1488:1492	arg1	number					1415:1420	the number	1411:1420	the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells	1411:1492	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	2	19	theme	coordinated	470:480	arg1	signaling					482:490	multiple coordinated signaling	461:490	multiple coordinated signaling that maintains the stemness of CSCs	461:526	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	0	20	theme	cancer	57:62	arg1	cells					69:73	human ALDH+ breast cancer stem cells	38:73	human ALDH+ breast cancer stem cells	38:73	Glucosamine decreases the stemness of human ALDH+ breast cancer stem cells by inactivating STAT3.
30214607	5	21	theme	exclusion	1043:1051	arg1	assay					1053:1057	a trypan blue exclusion assay	1029:1057	a trypan blue exclusion assay	1029:1057	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	3	22	theme	N-linked	592:599	arg1	glycosylation					601:613	N-linked glycosylation	592:613	N-linked glycosylation	592:613	Glucosamine acts as an anticancer agent possibly by inhibiting N-linked glycosylation.
30214607	6	23	theme	ALDH+	1461:1465	arg1	CSCs					1474:1477	ALDH+ breast CSCs	1461:1477	ALDH+ breast CSCs	1461:1477	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	0	24	theme	cells	69:73	arg1	stemness					26:33	the stemness	22:33	the stemness of human ALDH+ breast cancer stem cells	22:73	Glucosamine decreases the stemness of human ALDH+ breast cancer stem cells by inactivating STAT3.
30214607	8	25	theme	decreased	1704:1712	arg1	ALDH1A1					1714:1720	decreased ALDH1A1	1704:1720	decreased ALDH1A1	1704:1720	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	5	26	theme	Krüppel-like	1166:1177	arg1	factor					1179:1184	Krüppel-like factor 4	1166:1186	Krüppel-like factor 4 (KLF4)	1166:1193	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	26	theme	Krüppel-like	1166:1177	arg1	KLF4					1189:1192	KLF4	1189:1192	KLF4	1189:1192	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	6	27	from	units	1445:1449	arg1	CSCs					1474:1477	ALDH+ breast CSCs	1461:1477	ALDH+ breast CSCs	1461:1477	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	6	27	from	units	1445:1449	arg1	cells					1488:1492	MCF7 cells	1483:1492	MCF7 cells	1483:1492	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	7	28	theme	CSCs	1595:1598	arg1	viability					1569:1577	the viability	1565:1577	the viability of ALDH+ breast CSCs	1565:1598	It was determined that glucosamine treatment decreased the viability of ALDH+ breast CSCs.
30214607	5	29	theme	transcription	1130:1142	arg1	factor					1144:1149	octamer-binding transcription factor 4	1114:1151	octamer-binding transcription factor 4 (OCT-4)	1114:1159	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	29	theme	transcription	1130:1142	arg1	OCT-4					1154:1158	OCT-4	1154:1158	OCT-4	1154:1158	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	30	theme	trypan	1031:1036	arg1	assay					1053:1057	a trypan blue exclusion assay	1029:1057	a trypan blue exclusion assay	1029:1057	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	7	31	theme	ALDH+	1582:1586	arg1	CSCs					1595:1598	ALDH+ breast CSCs	1582:1598	ALDH+ breast CSCs	1582:1598	It was determined that glucosamine treatment decreased the viability of ALDH+ breast CSCs.
30214607	5	32	theme	western	1375:1381	arg1	analysis					1388:1395	western blot analysis	1375:1395	western blot analysis	1375:1395	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	4	33	theme	breast	709:714	arg1	CSCs					716:719	breast CSCs	709:719	breast CSCs	709:719	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	5	34	theme	reverse	1232:1238	arg1	reaction					1284:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	2	35	theme	alternative	335:345	arg1	strategy					347:354	an alternative strategy	332:354	an alternative strategy that targets post-translational glycosylation	332:400	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	2	35	theme	alternative	335:345	arg1	approach					421:428	an improved approach	409:428	an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs	409:526	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	5	36	theme	member	1093:1098	arg1	A1					1100:1101	pluripotency gene [ALDH 1 family member A1	1060:1101	pluripotency gene [ALDH 1 family member A1 (ALDH1A1)	1060:1111	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	36	theme	member	1093:1098	arg1	ALDH1A1					1104:1110	ALDH1A1	1104:1110	ALDH1A1	1104:1110	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	8	37	theme	expression	1738:1747	arg1	level					1749:1753	KLF4 expression level	1733:1753	KLF4 expression level	1733:1753	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	8	38	theme	cells	1681:1685	arg1	stemness					1642:1649	the stemness	1638:1649	the stemness of ALDH+ breast CSCs and MCF7 cells	1638:1685	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	1	39	theme	Cancer	98:103	arg1	CSCs					117:120	CSCs	117:120	CSCs	117:120	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	1	39	theme	Cancer	98:103	arg1	cells					110:114	Cancer stem cells	98:114	Cancer stem cells (CSCs)	98:121	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	1	39	theme	Cancer	98:103	arg1	subpopulation					129:141	a subpopulation	127:141	a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects	127:261	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	5	40	dep	assay	1053:1057	arg1	determined					1211:1220	determined	1211:1220	was determined using the reverse transcription-quantitative polymerase chain reaction	1207:1291	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	4	41	theme	transcription	779:791	arg1	STAT3					796:800	STAT3	796:800	STAT3	796:800	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	4	41	theme	transcription	779:791	arg1	activator					766:774	activator	766:774	activator	766:774	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	4	41	theme	transcription	779:791	arg1	transducer					751:760	signal transducer	744:760	signal transducer	744:760	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	2	42	theme	post-translational	369:386	arg1	glycosylation					388:400	post-translational glycosylation	369:400	post-translational glycosylation	369:400	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	5	43	theme	gene	1073:1076	arg1	A1					1100:1101	pluripotency gene [ALDH 1 family member A1	1060:1101	pluripotency gene [ALDH 1 family member A1 (ALDH1A1)	1060:1111	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	43	theme	gene	1073:1076	arg1	ALDH1A1					1104:1110	ALDH1A1	1104:1110	ALDH1A1	1104:1110	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	44	theme	glucosamine	949:959	arg1	mM					942:943	0.25, 1 or 4 mM	929:943	0.25, 1 or 4 mM	929:943	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	44	theme	glucosamine	949:959	arg1	concentrations					913:926	various concentrations	905:926	various concentrations (0.25, 1 or 4 mM) of glucosamine	905:959	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	9	45	theme	present	1956:1962	arg1	study					1964:1968	the present study	1952:1968	the present study	1952:1968	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	0	46	theme	ALDH+	44:48	arg1	cells					69:73	human ALDH+ breast cancer stem cells	38:73	human ALDH+ breast cancer stem cells	38:73	Glucosamine decreases the stemness of human ALDH+ breast cancer stem cells by inactivating STAT3.
30214607	4	47	theme	transducer	751:760	arg1	signaling					803:811	signal transducer and activator of transcription 3 (STAT3) signaling	744:811	signal transducer and activator of transcription 3 (STAT3) signaling	744:811	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	5	48	theme	factor	1144:1149	arg1	expression					1196:1205	pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression	1060:1205	pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression	1060:1205	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	9	49	theme	glucosamine	1985:1995	arg1	approach					2026:2033	an improved approach	2014:2033	an improved approach to target the stemness of CSCs	2014:2064	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	9	49	theme	glucosamine	1985:1995	arg1	treatment					1997:2005	glucosamine treatment	1985:2005	glucosamine treatment	1985:2005	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	4	50	theme	activator	766:774	arg1	signaling					803:811	signal transducer and activator of transcription 3 (STAT3) signaling	744:811	signal transducer and activator of transcription 3 (STAT3) signaling	744:811	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	5	51	theme	polymerase	1267:1276	arg1	reaction					1284:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	52	theme	aldehyde	820:827	arg1	CSCs					867:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	2	53	theme	targeted	314:321	arg1	therapy					323:329	targeted therapy	314:329	targeted therapy	314:329	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	4	54	from	effect	668:673	arg1	stemness					697:704	the stemness	693:704	the stemness	693:704	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	5	55	theme	octamer-binding	1114:1128	arg1	factor					1144:1149	octamer-binding transcription factor 4	1114:1151	octamer-binding transcription factor 4 (OCT-4)	1114:1159	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	55	theme	octamer-binding	1114:1128	arg1	OCT-4					1154:1158	OCT-4	1154:1158	OCT-4	1154:1158	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	56	theme	breast	860:865	arg1	CSCs					867:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	57	theme	dehydrogenase-positive	829:850	arg1	CSCs					867:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	58	theme	Human	814:818	arg1	CSCs					867:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	4	59	theme	present	631:637	arg1	study					639:643	the present study	627:643	the present study	627:643	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	8	60	theme	MFUs	1782:1785	arg1	ALDH1A1					1714:1720	decreased ALDH1A1	1704:1720	decreased ALDH1A1	1704:1720	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	8	60	theme	MFUs	1782:1785	arg1	number					1772:1777	a decreased number	1760:1777	a decreased number of MFUs	1760:1785	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	8	60	theme	MFUs	1782:1785	arg1	level					1749:1753	KLF4 expression level	1733:1753	KLF4 expression level	1733:1753	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	8	60	theme	MFUs	1782:1785	arg1	OCT-4					1723:1727	OCT-4	1723:1727	OCT-4	1723:1727	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	5	61	theme	STAT3	1323:1327	arg1	levels					1338:1343	STAT3 and phosphorylated STAT3 (pSTAT3) levels	1298:1343	STAT3 and phosphorylated STAT3 (pSTAT3) levels	1298:1343	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	6	62	theme	units	1445:1449	arg1	number					1415:1420	the number	1411:1420	the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells	1411:1492	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	1	63	theme	cells	153:157	arg1	cells					110:114	Cancer stem cells	98:114	Cancer stem cells (CSCs)	98:121	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	1	63	theme	cells	153:157	arg1	subpopulation					129:141	a subpopulation	127:141	a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects	127:261	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	7	64	theme	glucosamine	1533:1543	arg1	treatment					1545:1553	glucosamine treatment	1533:1553	glucosamine treatment	1533:1553	It was determined that glucosamine treatment decreased the viability of ALDH+ breast CSCs.
30214607	9	65	theme	glucosamine	1803:1813	arg1	effect					1793:1798	This effect	1788:1798	This effect of glucosamine	1788:1813	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	2	66	theme	CSCs	523:526	arg1	stemness					511:518	the stemness	507:518	the stemness of CSCs	507:526	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	9	67	theme	CSCs	2061:2064	arg1	stemness					2049:2056	the stemness	2045:2056	the stemness of CSCs	2045:2064	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	3	68	theme	anticancer	552:561	arg1	agent					563:567	an anticancer agent	549:567	an anticancer agent	549:567	Glucosamine acts as an anticancer agent possibly by inhibiting N-linked glycosylation.
30214607	3	68	theme	anticancer	552:561	arg1	Glucosamine					529:539	Glucosamine	529:539	Glucosamine	529:539	Glucosamine acts as an anticancer agent possibly by inhibiting N-linked glycosylation.
30214607	8	69	theme	breast	1660:1665	arg1	CSCs					1667:1670	ALDH+ breast CSCs	1654:1670	ALDH+ breast CSCs	1654:1670	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	1	70	theme	stem	105:108	arg1	CSCs					117:120	CSCs	117:120	CSCs	117:120	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	1	70	theme	stem	105:108	arg1	cells					110:114	Cancer stem cells	98:114	Cancer stem cells (CSCs)	98:121	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	1	70	theme	stem	105:108	arg1	subpopulation					129:141	a subpopulation	127:141	a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects	127:261	Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects.
30214607	9	71	theme	decreased	1840:1848	arg1	ratio					1863:1867	a decreased pSTAT3/STAT3 ratio	1838:1867	a decreased pSTAT3/STAT3 ratio	1838:1867	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	4	72	theme	glucosamine	678:688	arg1	effect					668:673	the effect	664:673	the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling	664:811	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	5	73	theme	factor	1179:1184	arg1	expression					1196:1205	pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression	1060:1205	pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression	1060:1205	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	0	74	theme	stem	64:67	arg1	cells					69:73	human ALDH+ breast cancer stem cells	38:73	human ALDH+ breast cancer stem cells	38:73	Glucosamine decreases the stemness of human ALDH+ breast cancer stem cells by inactivating STAT3.
30214607	5	75	theme	cell	985:988	arg1	viability					990:998	cell viability	985:998	cell viability	985:998	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	6	76	theme	breast	1467:1472	arg1	CSCs					1474:1477	ALDH+ breast CSCs	1461:1477	ALDH+ breast CSCs	1461:1477	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	5	77	theme	ALDH+	853:857	arg1	CSCs					867:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs	814:870	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	2	78	theme	multiple	461:468	arg1	signaling					482:490	multiple coordinated signaling	461:490	multiple coordinated signaling that maintains the stemness of CSCs	461:526	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	6	79	from	CSCs	1474:1477	arg1	number					1415:1420	the number	1411:1420	the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells	1411:1492	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	5	80	theme	pluripotency	1060:1071	arg1	A1					1100:1101	pluripotency gene [ALDH 1 family member A1	1060:1101	pluripotency gene [ALDH 1 family member A1 (ALDH1A1)	1060:1111	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	80	theme	pluripotency	1060:1071	arg1	ALDH1A1					1104:1110	ALDH1A1	1104:1110	ALDH1A1	1104:1110	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	9	81	theme	STAT3	1908:1912	arg1	activation					1914:1923	STAT3 activation	1908:1923	STAT3 activation	1908:1923	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	5	82	theme	blue	1038:1041	arg1	assay					1053:1057	a trypan blue exclusion assay	1029:1057	a trypan blue exclusion assay	1029:1057	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	8	83	theme	Glucosamine	1601:1611	arg1	treatment					1613:1621	Glucosamine treatment	1601:1621	Glucosamine treatment	1601:1621	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	6	84	from	number	1415:1420	arg1	CSCs					1474:1477	ALDH+ breast CSCs	1461:1477	ALDH+ breast CSCs	1461:1477	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	6	84	from	number	1415:1420	arg1	cells					1488:1492	MCF7 cells	1483:1492	MCF7 cells	1483:1492	Furthermore, the number of mammosphere-forming units (MFUs) in ALDH+ breast CSCs and MCF7 cells was determined.
30214607	7	85	theme	breast	1588:1593	arg1	CSCs					1595:1598	ALDH+ breast CSCs	1582:1598	ALDH+ breast CSCs	1582:1598	It was determined that glucosamine treatment decreased the viability of ALDH+ breast CSCs.
30214607	3	86	link	N-linked	592:599	arg1	glycosylation					601:613	N-linked glycosylation	592:613	N-linked glycosylation	592:613	Glucosamine acts as an anticancer agent possibly by inhibiting N-linked glycosylation.
30214607	5	87	theme	blot	1383:1386	arg1	analysis					1388:1395	western blot analysis	1375:1395	western blot analysis	1375:1395	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	88	theme	A1	1100:1101	arg1	expression					1196:1205	pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression	1060:1205	pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression	1060:1205	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	8	89	theme	KLF4	1733:1736	arg1	level					1749:1753	KLF4 expression level	1733:1753	KLF4 expression level	1733:1753	Glucosamine treatment also decreased the stemness of ALDH+ breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs.
30214607	5	90	theme	various	905:911	arg1	mM					942:943	0.25, 1 or 4 mM	929:943	0.25, 1 or 4 mM	929:943	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	90	theme	various	905:911	arg1	concentrations					913:926	various concentrations	905:926	various concentrations (0.25, 1 or 4 mM) of glucosamine	905:959	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	4	91	theme	CSCs	716:719	arg1	stemness					697:704	the stemness	693:704	the stemness	693:704	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	0	92	theme	human	38:42	arg1	cells					69:73	human ALDH+ breast cancer stem cells	38:73	human ALDH+ breast cancer stem cells	38:73	Glucosamine decreases the stemness of human ALDH+ breast cancer stem cells by inactivating STAT3.
30214607	9	93	dep	inhibited	1898:1906	arg1	indicated					1970:1978	indicated	1970:1978	indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs	1970:2064	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	0	94	theme	breast	50:55	arg1	cells					69:73	human ALDH+ breast cancer stem cells	38:73	human ALDH+ breast cancer stem cells	38:73	Glucosamine decreases the stemness of human ALDH+ breast cancer stem cells by inactivating STAT3.
30214607	5	95	theme	[ALDH	1078:1082	arg1	A1					1100:1101	pluripotency gene [ALDH 1 family member A1	1060:1101	pluripotency gene [ALDH 1 family member A1 (ALDH1A1)	1060:1111	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	95	theme	[ALDH	1078:1082	arg1	ALDH1A1					1104:1110	ALDH1A1	1104:1110	ALDH1A1	1104:1110	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	9	96	theme	study	1964:1968	arg1	results					1941:1947	the results	1937:1947	the results of the present study	1937:1968	This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.
30214607	5	97	theme	STAT3	1298:1302	arg1	levels					1338:1343	STAT3 and phosphorylated STAT3 (pSTAT3) levels	1298:1343	STAT3 and phosphorylated STAT3 (pSTAT3) levels	1298:1343	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	98	theme	family	1086:1091	arg1	A1					1100:1101	pluripotency gene [ALDH 1 family member A1	1060:1101	pluripotency gene [ALDH 1 family member A1 (ALDH1A1)	1060:1111	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	5	98	theme	family	1086:1091	arg1	ALDH1A1					1104:1110	ALDH1A1	1104:1110	ALDH1A1	1104:1110	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	4	99	theme	signal	744:749	arg1	STAT3					796:800	STAT3	796:800	STAT3	796:800	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	4	99	theme	signal	744:749	arg1	transducer					751:760	signal transducer	744:760	signal transducer	744:760	The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling.
30214607	5	100	theme	transcription-quantitative	1240:1265	arg1	reaction					1284:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	2	101	theme	CSCs	291:294	arg1	resistance					277:286	the resistance	273:286	the resistance of CSCs to the effects of targeted therapy	273:329	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
30214607	5	102	theme	chain	1278:1282	arg1	reaction					1284:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	the reverse transcription-quantitative polymerase chain reaction	1228:1291	Human aldehyde dehydrogenase-positive (ALDH+) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 (ALDH1A1), octamer-binding transcription factor 4 (OCT-4), and Krüppel-like factor 4 (KLF4)] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis.
30214607	2	103	theme	therapy	323:329	arg1	effects					303:309	the effects	299:309	the effects of targeted therapy	299:329	Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs.
29427717	0	0	from	protein	47:53	arg1	response					116:123	response	116:123	response to immune stimulation	116:145	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	9	1	theme	few	1182:1184	arg1	acids					1192:1196	the first few amino acids	1172:1196	the first few amino acids in the second beta sheet starting from the N-terminus	1172:1250	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	13	2	from	gene	1776:1779	arg1	seahorse					1784:1791	seahorse	1784:1791	seahorse	1784:1791	Thus, the ShTXNL1 gene may be identified as an immunologically important gene in seahorse.
29427717	11	3	theme	chain	1431:1435	arg1	reaction					1437:1444	the quantitative real-time polymerase chain reaction	1393:1444	the quantitative real-time polymerase chain reaction analysis from healthy seahorses	1393:1476	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	11	4	located	observed	1515:1522	arg1	muscle					1527:1532	muscle	1527:1532	muscle	1527:1532	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	11	4	located	observed	1515:1522	arg2	expression					1500:1509	highest ShTXNL1 mRNA expression	1479:1509	highest ShTXNL1 mRNA expression	1479:1509	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	8	5	theme	alignment	981:989	arg1	results					991:997	Pairwise alignment results	972:997	Pairwise alignment results	972:997	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	11	6	theme	real-time	1410:1418	arg1	reaction					1437:1444	the quantitative real-time polymerase chain reaction	1393:1444	the quantitative real-time polymerase chain reaction analysis from healthy seahorses	1393:1476	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	5	7	theme	seahorse	602:609	arg1	protein					628:634	seahorse thioredoxin-like protein 1	602:636	seahorse thioredoxin-like protein 1 (ShTXNL1)	602:646	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	5	7	theme	seahorse	602:609	arg1	ShTXNL1					639:645	ShTXNL1	639:645	ShTXNL1	639:645	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	5	8	theme	protein	628:634	arg1	experiments					564:574	immune challenge experiments	547:574	immune challenge experiments	547:574	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	5	8	theme	protein	628:634	arg1	assays					592:597	functional assays	581:597	functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1)	581:646	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	5	8	theme	protein	628:634	arg1	analysis					537:544	in-silico analysis	527:544	in-silico analysis	527:544	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	9	9	theme	beta	1212:1215	arg1	sheet					1217:1221	the second beta sheet	1201:1221	the second beta sheet starting from the N-terminus	1201:1250	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	7	10	theme	proteasome-interacting	840:861	arg1	PITH					883:886	PITH	883:886	PITH	883:886	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	10	theme	proteasome-interacting	840:861	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	10	theme	proteasome-interacting	840:861	arg1	domain					875:880	C-terminal proteasome-interacting thioredoxin domain	829:880	C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	829:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	11	theme	proteasome	928:937	arg1	component					911:919	a component	909:919	a component of 26S proteasome	909:937	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	11	theme	proteasome	928:937	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	8	12	theme	%	1010:1010	arg1	identity					1012:1019	99.0% identity	1006:1019	99.0% identity	1006:1019	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	2	13	theme	metabolic	290:298	arg1	processes					300:308	metabolic processes	290:308	metabolic processes	290:308	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	11	14	theme	highest	1479:1485	arg1	expression					1500:1509	highest ShTXNL1 mRNA expression	1479:1509	highest ShTXNL1 mRNA expression	1479:1509	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	12	15	theme	temporal	1608:1615	arg1	expression					1617:1626	significant temporal expression	1596:1626	significant temporal expression of ShTXNL1	1596:1637	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29427717	2	16	theme	oxygen	241:246	arg1	ROS					257:259	ROS	257:259	ROS	257:259	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	2	16	theme	oxygen	241:246	arg1	species					248:254	Reactive oxygen species	232:254	Reactive oxygen species (ROS)	232:260	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	13	17	theme	important	1766:1774	arg1	gene					1776:1779	an immunologically important gene	1747:1779	an immunologically important gene in seahorse	1747:1791	Thus, the ShTXNL1 gene may be identified as an immunologically important gene in seahorse.
29427717	13	17	theme	important	1766:1774	arg1	gene					1721:1724	the ShTXNL1 gene	1709:1724	the ShTXNL1 gene	1709:1724	Thus, the ShTXNL1 gene may be identified as an immunologically important gene in seahorse.
29427717	2	18	dep	processes	300:308	arg1	response					278:285	response	278:285	response	278:285	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	5	19	theme	in-silico	527:535	arg1	analysis					537:544	in-silico analysis	527:544	in-silico analysis	527:544	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	12	20	located	observed	1643:1650	arg2	expression					1617:1626	significant temporal expression	1596:1626	significant temporal expression of ShTXNL1	1596:1637	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29427717	12	20	located	observed	1643:1650	arg1	gill					1655:1658	gill	1655:1658	gill	1655:1658	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29427717	12	20	located	observed	1643:1650	arg1	blood					1664:1668	blood	1664:1668	blood	1664:1668	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29427717	9	21	theme	cysteine	1110:1117	arg1	residue					1119:1125	Conserved thiol-disulfide cysteine residue	1084:1125	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif	1084:1154	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	9	22	from	acids	1192:1196	arg1	sheet					1217:1221	the second beta sheet	1201:1221	the second beta sheet starting from the N-terminus	1201:1250	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	6	23	theme	289	755:757	arg1	acids					765:769	289 amino acids	755:769	289 amino acids	755:769	Evolutionary identification showed that ShTXNL1 protein belongs to the thioredoxin superfamily comprising 289 amino acids.
29427717	0	24	theme	big-belly	70:78	arg1	abdominalis					101:111	big-belly seahorse Hippocampus abdominalis	70:111	big-belly seahorse Hippocampus abdominalis	70:111	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	10	25	gly	glycosylation	1332:1344	arg2	two					1319:1321	two	1319:1321	two	1319:1321	This motif can be discovered in ShTXNL1 as 14CRPC17 and comprised two N-linked glycosylation sites at 72NISA75 and 139NESD142.
29427717	10	25	gly	glycosylation	1332:1344	arg2	sites					1346:1350	two N-linked glycosylation sites	1319:1350	two N-linked glycosylation sites	1319:1350	This motif can be discovered in ShTXNL1 as 14CRPC17 and comprised two N-linked glycosylation sites at 72NISA75 and 139NESD142.
29427717	0	26	theme	Hippocampus	89:99	arg1	abdominalis					101:111	big-belly seahorse Hippocampus abdominalis	70:111	big-belly seahorse Hippocampus abdominalis	70:111	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	9	27	contain	containing	1127:1136	arg1	residue					1119:1125	Conserved thiol-disulfide cysteine residue	1084:1125	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif	1084:1154	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	9	27	contain	containing	1127:1136	arg2	motif					1150:1154	Cys-X-X-Cys motif	1138:1154	Cys-X-X-Cys motif	1138:1154	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	8	28	theme	%	1029:1029	arg1	similarity					1031:1040	99.7% similarity	1025:1040	99.7% similarity	1025:1040	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	5	29	theme	functional	581:590	arg1	assays					592:597	functional assays	581:597	functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1)	581:646	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	11	30	dep	observed	1515:1522	arg1	followed					1535:1542	followed	1535:1542	followed by ovary, brain, gill, and blood tissues	1535:1583	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	11	31	theme	healthy	1460:1466	arg1	seahorses					1468:1476	healthy seahorses	1460:1476	healthy seahorses	1460:1476	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	4	32	theme	regulatory	460:469	arg1	thioredoxin					430:440	thioredoxin	430:440	thioredoxin	430:440	However, thioredoxin acts as an active regulatory enzyme in response to excessive ROS.
29427717	4	32	theme	regulatory	460:469	arg1	enzyme					471:476	an active regulatory enzyme	450:476	an active regulatory enzyme in response to excessive ROS	450:505	However, thioredoxin acts as an active regulatory enzyme in response to excessive ROS.
29427717	9	33	theme	Conserved	1084:1092	arg1	residue					1119:1125	Conserved thiol-disulfide cysteine residue	1084:1125	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif	1084:1154	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	0	34	theme	Molecular	0:8	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.	0:146	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	7	35	theme	thioredoxin	806:816	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	35	theme	thioredoxin	806:816	arg1	domain					818:823	an N-terminal active thioredoxin domain	785:823	an N-terminal active thioredoxin domain	785:823	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	5	36	theme	challenge	554:562	arg1	experiments					564:574	immune challenge experiments	547:574	immune challenge experiments	547:574	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	12	37	theme	ShTXNL1	1631:1637	arg1	expression					1617:1626	significant temporal expression	1596:1626	significant temporal expression of ShTXNL1	1596:1637	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29427717	3	38	theme	High	368:371	arg1	levels					373:378	High levels	368:378	High levels of ROS	368:385	High levels of ROS lead to cell death via autophagy.
29427717	11	39	theme	ShTXNL1	1487:1493	arg1	expression					1500:1509	highest ShTXNL1 mRNA expression	1479:1509	highest ShTXNL1 mRNA expression	1479:1509	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	7	40	theme	N-terminal	788:797	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	40	theme	N-terminal	788:797	arg1	domain					818:823	an N-terminal active thioredoxin domain	785:823	an N-terminal active thioredoxin domain	785:823	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	8	41	theme	Hippocampus	1063:1073	arg1	species					1075:1081	Hippocampus species	1063:1081	Hippocampus species	1063:1081	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	3	42	theme	cell	395:398	arg1	death					400:404	cell death	395:404	cell death	395:404	High levels of ROS lead to cell death via autophagy.
29427717	0	43	theme	protein	47:53	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.	0:146	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	6	44	theme	amino	759:763	arg1	acids					765:769	289 amino acids	755:769	289 amino acids	755:769	Evolutionary identification showed that ShTXNL1 protein belongs to the thioredoxin superfamily comprising 289 amino acids.
29427717	2	45	theme	metal	322:326	arg1	oxidation					328:336	metal oxidation	322:336	metal oxidation	322:336	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	7	46	theme	26S	924:926	arg1	proteasome					928:937	26S proteasome	924:937	26S proteasome	924:937	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	10	47	link	N-linked	1323:1330	arg1	sites					1346:1350	two N-linked glycosylation sites	1319:1350	two N-linked glycosylation sites	1319:1350	This motif can be discovered in ShTXNL1 as 14CRPC17 and comprised two N-linked glycosylation sites at 72NISA75 and 139NESD142.
29427717	6	48	theme	thioredoxin	720:730	arg1	superfamily					732:742	the thioredoxin superfamily	716:742	the thioredoxin superfamily comprising 289 amino acids	716:769	Evolutionary identification showed that ShTXNL1 protein belongs to the thioredoxin superfamily comprising 289 amino acids.
29427717	9	49	theme	first	1176:1180	arg1	acids					1192:1196	the first few amino acids	1172:1196	the first few amino acids in the second beta sheet starting from the N-terminus	1172:1250	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	2	50	theme	pathological	343:354	arg1	infections					356:365	pathological infections	343:365	pathological infections	343:365	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	8	51	theme	Pairwise	972:979	arg1	results					991:997	Pairwise alignment results	972:997	Pairwise alignment results	972:997	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	11	52	theme	polymerase	1420:1429	arg1	reaction					1437:1444	the quantitative real-time polymerase chain reaction	1393:1444	the quantitative real-time polymerase chain reaction analysis from healthy seahorses	1393:1476	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	9	53	theme	amino	1186:1190	arg1	acids					1192:1196	the first few amino acids	1172:1196	the first few amino acids in the second beta sheet starting from the N-terminus	1172:1250	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	7	54	theme	ShTXNL1	892:898	arg1	PITH					883:886	PITH	883:886	PITH	883:886	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	54	theme	ShTXNL1	892:898	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	54	theme	ShTXNL1	892:898	arg1	domain					875:880	C-terminal proteasome-interacting thioredoxin domain	829:880	C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	829:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	54	theme	ShTXNL1	892:898	arg1	domain					818:823	an N-terminal active thioredoxin domain	785:823	an N-terminal active thioredoxin domain	785:823	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	10	55	theme	glycosylation	1332:1344	arg1	sites					1346:1350	two N-linked glycosylation sites	1319:1350	two N-linked glycosylation sites	1319:1350	This motif can be discovered in ShTXNL1 as 14CRPC17 and comprised two N-linked glycosylation sites at 72NISA75 and 139NESD142.
29427717	11	56	theme	quantitative	1397:1408	arg1	reaction					1437:1444	the quantitative real-time polymerase chain reaction	1393:1444	the quantitative real-time polymerase chain reaction analysis from healthy seahorses	1393:1476	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	4	57	from	enzyme	471:476	arg1	response					481:488	response	481:488	response to excessive ROS	481:505	However, thioredoxin acts as an active regulatory enzyme in response to excessive ROS.
29427717	1	58	theme	conserved	172:180	arg1	protein					182:188	a highly conserved protein	163:188	a highly conserved protein found in both prokaryotes and eukaryotes	163:229	Thioredoxin is a highly conserved protein found in both prokaryotes and eukaryotes.
29427717	1	58	theme	conserved	172:180	arg1	Thioredoxin					148:158	Thioredoxin	148:158	Thioredoxin	148:158	Thioredoxin is a highly conserved protein found in both prokaryotes and eukaryotes.
29427717	8	59	theme	99.0	1006:1009	arg1	%					1010:1010	%	1010:1010	%	1010:1010	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	7	60	contain	possesses	775:783	arg2	domain					818:823	an N-terminal active thioredoxin domain	785:823	an N-terminal active thioredoxin domain	785:823	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	60	contain	possesses	775:783	arg2	PITH					883:886	PITH	883:886	PITH	883:886	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	60	contain	possesses	775:783	arg1	It					772:773	It	772:773	It	772:773	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	60	contain	possesses	775:783	arg2	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	60	contain	possesses	775:783	arg2	domain					875:880	C-terminal proteasome-interacting thioredoxin domain	829:880	C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	829:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	5	61	theme	thioredoxin-like	611:626	arg1	protein					628:634	seahorse thioredoxin-like protein 1	602:636	seahorse thioredoxin-like protein 1 (ShTXNL1)	602:646	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	5	61	theme	thioredoxin-like	611:626	arg1	ShTXNL1					639:645	ShTXNL1	639:645	ShTXNL1	639:645	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	9	62	theme	second	1205:1210	arg1	sheet					1217:1221	the second beta sheet	1201:1221	the second beta sheet starting from the N-terminus	1201:1250	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	4	63	theme	excessive	493:501	arg1	ROS					503:505	excessive ROS	493:505	excessive ROS	493:505	However, thioredoxin acts as an active regulatory enzyme in response to excessive ROS.
29427717	12	64	theme	significant	1596:1606	arg1	expression					1617:1626	significant temporal expression	1596:1626	significant temporal expression of ShTXNL1	1596:1637	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29427717	0	65	theme	immune	128:133	arg1	stimulation					135:145	immune stimulation	128:145	immune stimulation	128:145	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	7	66	theme	thioredoxin	863:873	arg1	PITH					883:886	PITH	883:886	PITH	883:886	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	66	theme	thioredoxin	863:873	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	66	theme	thioredoxin	863:873	arg1	domain					875:880	C-terminal proteasome-interacting thioredoxin domain	829:880	C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	829:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	10	67	theme	N-linked	1323:1330	arg1	sites					1346:1350	two N-linked glycosylation sites	1319:1350	two N-linked glycosylation sites	1319:1350	This motif can be discovered in ShTXNL1 as 14CRPC17 and comprised two N-linked glycosylation sites at 72NISA75 and 139NESD142.
29427717	13	68	theme	ShTXNL1	1713:1719	arg1	gene					1721:1724	the ShTXNL1 gene	1709:1724	the ShTXNL1 gene	1709:1724	Thus, the ShTXNL1 gene may be identified as an immunologically important gene in seahorse.
29427717	13	68	theme	ShTXNL1	1713:1719	arg1	gene					1776:1779	an immunologically important gene	1747:1779	an immunologically important gene in seahorse	1747:1791	Thus, the ShTXNL1 gene may be identified as an immunologically important gene in seahorse.
29427717	7	69	theme	C-terminal	829:838	arg1	PITH					883:886	PITH	883:886	PITH	883:886	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	69	theme	C-terminal	829:838	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	69	theme	C-terminal	829:838	arg1	domain					875:880	C-terminal proteasome-interacting thioredoxin domain	829:880	C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	829:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	9	70	located	found	1163:1167	arg1	acids					1192:1196	the first few amino acids	1172:1196	the first few amino acids in the second beta sheet starting from the N-terminus	1172:1250	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	9	70	located	found	1163:1167	arg2	residue					1119:1125	Conserved thiol-disulfide cysteine residue	1084:1125	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif	1084:1154	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	1	71	located	found	190:194	arg1	prokaryotes					204:214	prokaryotes	204:214	prokaryotes	204:214	Thioredoxin is a highly conserved protein found in both prokaryotes and eukaryotes.
29427717	1	71	located	found	190:194	arg2	Thioredoxin					148:158	Thioredoxin	148:158	Thioredoxin	148:158	Thioredoxin is a highly conserved protein found in both prokaryotes and eukaryotes.
29427717	1	71	located	found	190:194	arg2	protein					182:188	a highly conserved protein	163:188	a highly conserved protein found in both prokaryotes and eukaryotes	163:229	Thioredoxin is a highly conserved protein found in both prokaryotes and eukaryotes.
29427717	1	71	located	found	190:194	arg1	eukaryotes					220:229	eukaryotes	220:229	eukaryotes	220:229	Thioredoxin is a highly conserved protein found in both prokaryotes and eukaryotes.
29427717	2	72	theme	Reactive	232:239	arg1	ROS					257:259	ROS	257:259	ROS	257:259	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	2	72	theme	Reactive	232:239	arg1	species					248:254	Reactive oxygen species	232:254	Reactive oxygen species (ROS)	232:260	Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections.
29427717	0	73	from	response	116:123	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.	0:146	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	0	74	from	abdominalis	101:111	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.	0:146	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	0	74	from	abdominalis	101:111	arg1	protein					47:53	thioredoxin-like protein 1	30:55	thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation	30:145	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	0	74	from	abdominalis	101:111	arg1	TXNL1					58:62	TXNL1	58:62	TXNL1	58:62	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	11	75	theme	mRNA	1495:1498	arg1	expression					1500:1509	highest ShTXNL1 mRNA expression	1479:1509	highest ShTXNL1 mRNA expression	1479:1509	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	0	76	theme	seahorse	80:87	arg1	abdominalis					101:111	big-belly seahorse Hippocampus abdominalis	70:111	big-belly seahorse Hippocampus abdominalis	70:111	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	8	77	theme	99.7	1025:1028	arg1	%					1029:1029	%	1029:1029	%	1029:1029	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	0	78	from	characterization	10:25	arg1	abdominalis					101:111	big-belly seahorse Hippocampus abdominalis	70:111	big-belly seahorse Hippocampus abdominalis	70:111	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	0	78	from	characterization	10:25	arg1	response					116:123	response	116:123	response to immune stimulation	116:145	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	12	79	theme	bacterial	1684:1692	arg1	stimuli					1694:1700	bacterial stimuli	1684:1700	bacterial stimuli	1684:1700	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29427717	4	80	theme	active	453:458	arg1	thioredoxin					430:440	thioredoxin	430:440	thioredoxin	430:440	However, thioredoxin acts as an active regulatory enzyme in response to excessive ROS.
29427717	4	80	theme	active	453:458	arg1	enzyme					471:476	an active regulatory enzyme	450:476	an active regulatory enzyme in response to excessive ROS	450:505	However, thioredoxin acts as an active regulatory enzyme in response to excessive ROS.
29427717	6	81	theme	ShTXNL1	689:695	arg1	protein					697:703	ShTXNL1 protein	689:703	ShTXNL1 protein	689:703	Evolutionary identification showed that ShTXNL1 protein belongs to the thioredoxin superfamily comprising 289 amino acids.
29427717	5	82	theme	immune	547:552	arg1	experiments					564:574	immune challenge experiments	547:574	immune challenge experiments	547:574	Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1).
29427717	3	83	theme	ROS	383:385	arg1	levels					373:378	High levels	368:378	High levels of ROS	368:385	High levels of ROS lead to cell death via autophagy.
29427717	9	84	theme	thiol-disulfide	1094:1108	arg1	residue					1119:1125	Conserved thiol-disulfide cysteine residue	1084:1125	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif	1084:1154	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	0	85	theme	thioredoxin-like	30:45	arg1	protein					47:53	thioredoxin-like protein 1	30:55	thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation	30:145	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	0	85	theme	thioredoxin-like	30:45	arg1	TXNL1					58:62	TXNL1	58:62	TXNL1	58:62	Molecular characterization of thioredoxin-like protein 1 (TXNL1) from big-belly seahorse Hippocampus abdominalis in response to immune stimulation.
29427717	8	86	theme	species	1075:1081	arg1	sequence					1051:1058	the sequence	1047:1058	the sequence of Hippocampus species	1047:1081	Pairwise alignment results showed 99.0% identity and 99.7% similarity with the sequence of Hippocampus species.
29427717	6	87	theme	Evolutionary	649:660	arg1	identification					662:675	Evolutionary identification	649:675	Evolutionary identification	649:675	Evolutionary identification showed that ShTXNL1 protein belongs to the thioredoxin superfamily comprising 289 amino acids.
29427717	7	88	theme	active	799:804	arg1	ShTXNL1					892:898	ShTXNL1	892:898	ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell	892:969	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	7	88	theme	active	799:804	arg1	domain					818:823	an N-terminal active thioredoxin domain	785:823	an N-terminal active thioredoxin domain	785:823	It possesses an N-terminal active thioredoxin domain and C-terminal proteasome-interacting thioredoxin domain (PITH) of ShTXNL1 which is a component of 26S proteasome and binds to the matrix or cell.
29427717	11	89	from	seahorses	1468:1476	arg1	analysis					1446:1453	the quantitative real-time polymerase chain reaction analysis	1393:1453	the quantitative real-time polymerase chain reaction analysis from healthy seahorses	1393:1476	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	9	90	theme	Cys-X-X-Cys	1138:1148	arg1	motif					1150:1154	Cys-X-X-Cys motif	1138:1154	Cys-X-X-Cys motif	1138:1154	Conserved thiol-disulfide cysteine residue containing Cys-X-X-Cys motif may be found in the first few amino acids in the second beta sheet starting from the N-terminus.
29427717	11	91	theme	blood	1571:1575	arg1	tissues					1577:1583	blood tissues	1571:1583	blood tissues	1571:1583	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	11	92	theme	reaction	1437:1444	arg1	analysis					1446:1453	the quantitative real-time polymerase chain reaction analysis	1393:1453	the quantitative real-time polymerase chain reaction analysis from healthy seahorses	1393:1476	According to the quantitative real-time polymerase chain reaction analysis from healthy seahorses, highest ShTXNL1 mRNA expression was observed in muscle, followed by ovary, brain, gill, and blood tissues.
29427717	12	93	dep	gill	1655:1658	arg1	tissues					1670:1676	tissues	1670:1676	tissues	1670:1676	Moreover, significant temporal expression of ShTXNL1 was observed in gill and blood tissues after bacterial stimuli.
29327476	10	0	theme	IHC	1668:1670	arg1	scores					1672:1677	The IHC scores	1664:1677	The IHC scores of O-GlcNAc or OGT	1664:1696	The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading.
29327476	6	1	theme	normal	1010:1015	arg1	keratinocytes					1022:1034	normal oral keratinocytes	1010:1034	normal oral keratinocytes	1010:1034	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	9	2	theme	IHC	1500:1502	arg1	scores					1504:1509	the median IHC scores	1489:1509	the median IHC scores of O-GlcNAc and OGT	1489:1529	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	9	2	theme	IHC	1500:1502	arg1	lower					1550:1554	lower	1550:1554	lower	1550:1554	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	1	3	theme	O-linked	184:191	arg1	O-GlcNAc					216:223	O-GlcNAc	216:223	O-GlcNAc	216:223	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	1	3	theme	O-linked	184:191	arg1	β-N-acetylglucosamine					193:213	O-linked β-N-acetylglucosamine	184:213	O-linked β-N-acetylglucosamine (O-GlcNAc)	184:224	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	9	4	theme	O-GlcNAc	1514:1521	arg1	scores					1504:1509	the median IHC scores	1489:1509	the median IHC scores of O-GlcNAc and OGT	1489:1529	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	9	4	theme	O-GlcNAc	1514:1521	arg1	lower					1550:1554	lower	1550:1554	lower	1550:1554	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	8	5	theme	oral	1435:1438	arg1	keratinocytes					1440:1452	normal oral keratinocytes	1428:1452	normal oral keratinocytes	1428:1452	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	11	6	theme	oral	1914:1917	arg1	cells					1926:1930	oral cancer cells	1914:1930	oral cancer cells	1914:1930	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	3	7	theme	oral	517:520	arg1	keratinocytes					522:534	oral keratinocytes	517:534	oral keratinocytes	517:534	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	3	8	from	modifications	431:443	arg1	tissues					453:459	OSCC tissues	448:459	OSCC tissues	448:459	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	3	8	from	modifications	431:443	arg1	cells					480:484	oral cancer cells	468:484	oral cancer cells	468:484	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	4	9	theme	Thirty-two	619:628	arg1	OSCC					630:633	Thirty-two OSCC	619:633	Thirty-two OSCC	619:633	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	10	10	theme	OGT	1694:1696	arg1	scores					1672:1677	The IHC scores	1664:1677	The IHC scores of O-GlcNAc or OGT	1664:1696	The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading.
29327476	6	11	theme	cancer	993:998	arg1	cells					1000:1004	oral cancer cells	988:1004	oral cancer cells	988:1004	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	1	12	theme	post-translational	64:81	arg1	mechanisms					83:92	BACKGROUND Two post-translational mechanisms	49:92	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers	49:133	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	1	12	theme	post-translational	64:81	arg1	protein					139:145	protein phosphorylation and glycosylation	139:179	protein	139:145	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	10	13	theme	histological	1736:1747	arg1	grading					1749:1755	histological grading	1736:1755	histological grading	1736:1755	The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading.
29327476	2	14	theme	pathway	308:314	arg1	phosphorylation					241:255	only phosphorylation	236:255	only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway	236:314	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	8	15	theme	proteins	1394:1401	arg1	expression					1365:1374	expression	1365:1374	expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes	1365:1452	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	4	16	theme	anti-O-GlcNAc	732:744	arg1	OGT					759:761	OGT	759:761	OGT	759:761	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	16	theme	anti-O-GlcNAc	732:744	arg1	transferase					746:756	anti-O-GlcNAc transferase	732:756	anti-O-GlcNAc transferase (OGT)	732:762	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	16	theme	anti-O-GlcNAc	732:744	arg1	antibodies					833:842	the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies	713:842	antibodies	833:842	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	6	17	theme	oral	988:991	arg1	cells					1000:1004	oral cancer cells	988:1004	oral cancer cells	988:1004	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	5	18	dep	immunohistochemical	889:907	arg1	IHC					910:912	IHC	910:912	IHC	910:912	The immunohistochemical (IHC) score was determined using the Fromowitz standard.
29327476	8	19	theme	O-GlcNAcylated	1379:1392	arg1	proteins					1394:1401	O-GlcNAcylated proteins	1379:1401	O-GlcNAcylated proteins	1379:1401	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	2	20	theme	/Akt	303:306	arg1	pathway					308:314	the epidermal growth factor receptor (EGFR)/Akt pathway	260:314	the epidermal growth factor receptor (EGFR)/Akt pathway	260:314	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	10	21	theme	O-GlcNAc	1682:1689	arg1	scores					1672:1677	The IHC scores	1664:1677	The IHC scores of O-GlcNAc or OGT	1664:1696	The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading.
29327476	1	22	dep	protein	139:145	arg1	phosphorylation					147:161	phosphorylation	147:161	phosphorylation	147:161	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	7	23	theme	normal	1301:1306	arg1	tissues					1308:1314	normal tissues	1301:1314	normal tissues	1301:1314	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	11	24	theme	cancers	1791:1797	arg1	types					1782:1786	other types	1776:1786	other types of cancers	1776:1797	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	7	25	dep	higher	1281:1286	arg1	P < .01					1330:1336	P < .01	1330:1336	P < .01	1330:1336	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	7	25	dep	higher	1281:1286	arg1	P < .001					1317:1324	P < .001	1317:1324	P < .001	1317:1324	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	11	26	dep	CONCLUSION	1758:1767	arg1	types					1782:1786	other types	1776:1786	other types of cancers	1776:1797	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	2	27	theme	oral	337:340	arg1	carcinoma					356:364	oral squamous cell carcinoma	337:364	oral squamous cell carcinoma (OSCC)	337:371	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	2	27	theme	oral	337:340	arg1	OSCC					367:370	OSCC	367:370	OSCC	367:370	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	11	28	theme	histological	1964:1975	arg1	grading					1977:1983	the histological grading	1960:1983	the histological grading of OSCC	1960:1991	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	11	29	theme	OSCC	1895:1898	arg1	tissues					1900:1906	OSCC tissues	1895:1906	OSCC tissues	1895:1906	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	6	30	theme	keratinocytes	1022:1034	arg1	lysates					977:983	Whole cell lysates	966:983	Whole cell lysates of oral cancer cells and normal oral keratinocytes	966:1034	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	9	31	theme	OGT	1527:1529	arg1	scores					1504:1509	the median IHC scores	1489:1509	the median IHC scores of O-GlcNAc and OGT	1489:1529	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	9	31	theme	OGT	1527:1529	arg1	lower					1550:1554	lower	1550:1554	lower	1550:1554	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	3	32	theme	histological	589:600	arg1	grading					602:608	histological grading	589:608	histological grading	589:608	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	7	33	dep	RESULTS	1088:1094	arg1	different					1178:1186	different	1178:1186	different	1178:1186	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	7	33	dep	RESULTS	1088:1094	arg1	scores					1111:1116	The median IHC scores	1096:1116	The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues	1096:1167	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	3	34	theme	OSCC	448:451	arg1	tissues					453:459	OSCC tissues	448:459	OSCC tissues	448:459	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	0	35	theme	squamous	24:31	arg1	carcinoma					38:46	oral squamous cell carcinoma	19:46	oral squamous cell carcinoma	19:46	O-GlcNAcylation in oral squamous cell carcinoma.
29327476	1	36	link	O-linked	184:191	arg1	O-GlcNAc					216:223	O-GlcNAc	216:223	O-GlcNAc	216:223	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	1	36	link	O-linked	184:191	arg1	β-N-acetylglucosamine					193:213	O-linked β-N-acetylglucosamine	184:213	O-linked β-N-acetylglucosamine (O-GlcNAc)	184:224	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	1	37	theme	various	119:125	arg1	cancers					127:133	various cancers	119:133	various cancers	119:133	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	3	38	theme	cancer	473:478	arg1	cells					480:484	oral cancer cells	468:484	oral cancer cells	468:484	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	0	39	theme	oral	19:22	arg1	carcinoma					38:46	oral squamous cell carcinoma	19:46	oral squamous cell carcinoma	19:46	O-GlcNAcylation in oral squamous cell carcinoma.
29327476	6	40	theme	anti-O-GlcNAc	1064:1076	arg1	antibody					1078:1085	the anti-O-GlcNAc antibody	1060:1085	the anti-O-GlcNAc antibody	1060:1085	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	6	41	theme	cell	972:975	arg1	lysates					977:983	Whole cell lysates	966:983	Whole cell lysates of oral cancer cells and normal oral keratinocytes	966:1034	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	3	42	theme	modifications	570:582	arg1	correlations					548:559	correlations	548:559	correlations of these modifications with histological grading	548:608	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	4	43	theme	formalin-fixed	650:663	arg1	sections					687:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	3	44	theme	post-translational	412:429	arg1	modifications					431:443	both post-translational modifications	407:443	both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes	407:534	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	11	45	theme	cancer	1919:1924	arg1	cells					1926:1930	oral cancer cells	1914:1930	oral cancer cells	1914:1930	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	7	46	theme	normal	1154:1159	arg1	tissues					1161:1167	OSCC and normal tissues	1145:1167	tissues	1161:1167	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	4	47	dep	METHODS	611:617	arg1	sections					687:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	47	dep	METHODS	611:617	arg1	OSCC					630:633	Thirty-two OSCC	619:633	Thirty-two OSCC	619:633	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	2	48	theme	growth	274:279	arg1	receptor					288:295	epidermal growth factor receptor	264:295	the epidermal growth factor receptor (EGFR)/Akt pathway	260:314	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	2	48	theme	growth	274:279	arg1	EGFR					298:301	EGFR	298:301	EGFR	298:301	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	8	49	theme	oral	1406:1409	arg1	cells					1418:1422	oral cancer cells	1406:1422	oral cancer cells	1406:1422	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	0	50	theme	cell	33:36	arg1	carcinoma					38:46	oral squamous cell carcinoma	19:46	oral squamous cell carcinoma	19:46	O-GlcNAcylation in oral squamous cell carcinoma.
29327476	8	51	from	expression	1365:1374	arg1	keratinocytes					1440:1452	normal oral keratinocytes	1428:1452	normal oral keratinocytes	1428:1452	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	8	51	from	expression	1365:1374	arg1	cells					1418:1422	oral cancer cells	1406:1422	oral cancer cells	1406:1422	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	9	52	dep	phosphorylated-EGFRtyr1173	1570:1595	arg1	P < .001					1639:1646	P < .001	1639:1646	P < .001	1639:1646	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	9	52	dep	phosphorylated-EGFRtyr1173	1570:1595	arg1	P < .01					1627:1633	P < .01	1627:1633	P < .01	1627:1633	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	2	53	theme	epidermal	264:272	arg1	receptor					288:295	epidermal growth factor receptor	264:295	the epidermal growth factor receptor (EGFR)/Akt pathway	260:314	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	2	53	theme	epidermal	264:272	arg1	EGFR					298:301	EGFR	298:301	EGFR	298:301	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	7	54	theme	O-GlcNAc	1121:1128	arg1	different					1178:1186	different	1178:1186	different	1178:1186	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	7	54	theme	O-GlcNAc	1121:1128	arg1	scores					1111:1116	The median IHC scores	1096:1116	The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues	1096:1167	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	3	55	theme	oral	468:471	arg1	cells					480:484	oral cancer cells	468:484	oral cancer cells	468:484	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	3	56	with	correlations	548:559	arg1	grading					602:608	histological grading	589:608	histological grading	589:608	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	9	57	theme	OSCC	1477:1480	arg1	group					1482:1486	the OSCC group	1473:1486	the OSCC group	1473:1486	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	7	58	theme	OSCC	1145:1148	arg1	tissues					1161:1167	OSCC and normal tissues	1145:1167	tissues	1161:1167	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	0	59	dep	O-GlcNAcylation	0:14	arg1	carcinoma					38:46	oral squamous cell carcinoma	19:46	oral squamous cell carcinoma	19:46	O-GlcNAcylation in oral squamous cell carcinoma.
29327476	7	60	theme	OGT	1133:1135	arg1	different					1178:1186	different	1178:1186	different	1178:1186	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	7	60	theme	OGT	1133:1135	arg1	scores					1111:1116	The median IHC scores	1096:1116	The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues	1096:1167	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	3	61	theme	normal	498:503	arg1	tissues					505:511	normal tissues	498:511	normal tissues	498:511	Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.
29327476	6	62	theme	cells	1000:1004	arg1	lysates					977:983	Whole cell lysates	966:983	Whole cell lysates of oral cancer cells and normal oral keratinocytes	966:1034	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	11	63	theme	other	1776:1780	arg1	types					1782:1786	other types	1776:1786	other types of cancers	1776:1797	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	11	64	theme	O-GlcNAcylation	1844:1858	arg1	levels					1834:1839	the levels	1830:1839	the levels of O-GlcNAcylation	1830:1858	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	8	65	theme	cancer	1411:1416	arg1	cells					1418:1422	oral cancer cells	1406:1422	oral cancer cells	1406:1422	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	2	66	theme	factor	281:286	arg1	receptor					288:295	epidermal growth factor receptor	264:295	the epidermal growth factor receptor (EGFR)/Akt pathway	260:314	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	2	66	theme	factor	281:286	arg1	EGFR					298:301	EGFR	298:301	EGFR	298:301	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	4	67	dep	antibodies	833:842	arg1	OGT					759:761	OGT	759:761	OGT	759:761	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	67	dep	antibodies	833:842	arg1	anti-phosphorylated-EGFRtyr1173					765:795	anti-phosphorylated-EGFRtyr1173	765:795	anti-phosphorylated-EGFRtyr1173	765:795	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	67	dep	antibodies	833:842	arg1	transferase					746:756	anti-O-GlcNAc transferase	732:756	anti-O-GlcNAc transferase (OGT)	732:762	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	67	dep	antibodies	833:842	arg1	antibodies					833:842	the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies	713:842	antibodies	833:842	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	67	dep	antibodies	833:842	arg1	anti-phosphorylated-Aktser473					803:831	anti-phosphorylated-Aktser473	803:831	anti-phosphorylated-Aktser473	803:831	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	2	68	theme	only	236:239	arg1	phosphorylation					241:255	only phosphorylation	236:255	only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway	236:314	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	11	69	theme	OSCC	1988:1991	arg1	grading					1977:1983	the histological grading	1960:1983	the histological grading of OSCC	1960:1991	CONCLUSION Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.
29327476	2	70	theme	cell	351:354	arg1	carcinoma					356:364	oral squamous cell carcinoma	337:364	oral squamous cell carcinoma (OSCC)	337:371	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	2	70	theme	cell	351:354	arg1	OSCC					367:370	OSCC	367:370	OSCC	367:370	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	9	71	theme	median	1493:1498	arg1	scores					1504:1509	the median IHC scores	1489:1509	the median IHC scores of O-GlcNAc and OGT	1489:1529	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	9	71	theme	median	1493:1498	arg1	lower					1550:1554	lower	1550:1554	lower	1550:1554	In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 (P < .01 and P < .001, respectively).
29327476	4	72	theme	standard	854:861	arg1	immunohistochemistry					863:882	standard immunohistochemistry	854:882	standard immunohistochemistry	854:882	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	7	73	theme	median	1100:1105	arg1	different					1178:1186	different	1178:1186	different	1178:1186	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	7	73	theme	median	1100:1105	arg1	scores					1111:1116	The median IHC scores	1096:1116	The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues	1096:1167	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	2	74	theme	squamous	342:349	arg1	carcinoma					356:364	oral squamous cell carcinoma	337:364	oral squamous cell carcinoma (OSCC)	337:371	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	2	74	theme	squamous	342:349	arg1	OSCC					367:370	OSCC	367:370	OSCC	367:370	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	8	75	theme	normal	1428:1433	arg1	keratinocytes					1440:1452	normal oral keratinocytes	1428:1452	normal oral keratinocytes	1428:1452	Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ.
29327476	6	76	theme	Whole	966:970	arg1	lysates					977:983	Whole cell lysates	966:983	Whole cell lysates of oral cancer cells and normal oral keratinocytes	966:1034	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	4	77	theme	paraffin-embedded	669:685	arg1	sections					687:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	2	78	theme	receptor	288:295	arg1	pathway					308:314	the epidermal growth factor receptor (EGFR)/Akt pathway	260:314	the epidermal growth factor receptor (EGFR)/Akt pathway	260:314	However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC).
29327476	7	79	theme	IHC	1107:1109	arg1	different					1178:1186	different	1178:1186	different	1178:1186	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	7	79	theme	IHC	1107:1109	arg1	scores					1111:1116	The median IHC scores	1096:1116	The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues	1096:1167	RESULTS The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
29327476	4	80	theme	normal	643:648	arg1	sections					687:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	ten normal formalin-fixed and paraffin-embedded sections	639:694	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	5	81	theme	immunohistochemical	889:907	arg1	score					915:919	The immunohistochemical (IHC) score	885:919	The immunohistochemical (IHC) score	885:919	The immunohistochemical (IHC) score was determined using the Fromowitz standard.
29327476	6	82	theme	oral	1017:1020	arg1	keratinocytes					1022:1034	normal oral keratinocytes	1010:1034	normal oral keratinocytes	1010:1034	Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.
29327476	1	83	theme	BACKGROUND	49:58	arg1	mechanisms					83:92	BACKGROUND Two post-translational mechanisms	49:92	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers	49:133	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	1	83	theme	BACKGROUND	49:58	arg1	protein					139:145	protein phosphorylation and glycosylation	139:179	protein	139:145	BACKGROUND Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc).
29327476	4	84	theme	anti-O-GlcNAc	717:729	arg1	anti-phosphorylated-EGFRtyr1173					765:795	anti-phosphorylated-EGFRtyr1173	765:795	anti-phosphorylated-EGFRtyr1173	765:795	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	84	theme	anti-O-GlcNAc	717:729	arg1	transferase					746:756	anti-O-GlcNAc transferase	732:756	anti-O-GlcNAc transferase (OGT)	732:762	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	84	theme	anti-O-GlcNAc	717:729	arg1	anti-phosphorylated-Aktser473					803:831	anti-phosphorylated-Aktser473	803:831	anti-phosphorylated-Aktser473	803:831	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
29327476	4	84	theme	anti-O-GlcNAc	717:729	arg1	antibodies					833:842	the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies	713:842	antibodies	833:842	METHODS Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated-Aktser473 antibodies following standard immunohistochemistry.
31717261	4	0	theme	inflammation	488:499	arg1	severity					468:475	The severity	464:475	The severity of hepatic inflammation	464:499	The severity of hepatic inflammation was alleviated by curcumin treatment.
31717261	14	1	theme	therapeutic	1878:1888	arg1	agent					1890:1894	a promising therapeutic agent	1866:1894	a promising therapeutic agent for diseases involving hyper-O-GlcNAcylation, including cancer	1866:1957	Therefore, curcumin will be a promising therapeutic agent for diseases involving hyper-O-GlcNAcylation, including cancer.
31717261	14	1	theme	therapeutic	1878:1888	arg1	curcumin					1849:1856	curcumin	1849:1856	curcumin	1849:1856	Therefore, curcumin will be a promising therapeutic agent for diseases involving hyper-O-GlcNAcylation, including cancer.
31717261	7	2	theme	curcumin	900:907	arg1	treatment					909:917	curcumin treatment	900:917	curcumin treatment	900:917	However, the difference in expression was markedly improved by curcumin treatment.
31717261	5	3	theme	MCD	649:651	arg1	mice					658:661	MCD diet mice	649:661	MCD diet mice	649:661	To identify the proteins involved in the pathogenesis of NAFLD, we also characterized the hepatic proteome in MCD diet mice.
31717261	5	4	theme	NAFLD	596:600	arg1	pathogenesis					580:591	the pathogenesis	576:591	the pathogenesis of NAFLD	576:600	To identify the proteins involved in the pathogenesis of NAFLD, we also characterized the hepatic proteome in MCD diet mice.
31717261	14	5	theme	promising	1868:1876	arg1	agent					1890:1894	a promising therapeutic agent	1866:1894	a promising therapeutic agent for diseases involving hyper-O-GlcNAcylation, including cancer	1866:1957	Therefore, curcumin will be a promising therapeutic agent for diseases involving hyper-O-GlcNAcylation, including cancer.
31717261	14	5	theme	promising	1868:1876	arg1	curcumin					1849:1856	curcumin	1849:1856	curcumin	1849:1856	Therefore, curcumin will be a promising therapeutic agent for diseases involving hyper-O-GlcNAcylation, including cancer.
31717261	13	6	theme	O-GlcNAcylation	1734:1748	arg1	pathway					1750:1756	O-GlcNAcylation pathway	1734:1756	O-GlcNAcylation pathway	1734:1756	In conclusion, curcumin inhibits O-GlcNAcylation pathway, leading to antioxidant responses in non-alcoholic steatohepatitis (NASH) mice.
31717261	13	7	from	responses	1782:1790	arg1	mice					1832:1835	non-alcoholic steatohepatitis (NASH) mice	1795:1835	non-alcoholic steatohepatitis (NASH) mice	1795:1835	In conclusion, curcumin inhibits O-GlcNAcylation pathway, leading to antioxidant responses in non-alcoholic steatohepatitis (NASH) mice.
31717261	5	8	theme	diet	653:656	arg1	mice					658:661	MCD diet mice	649:661	MCD diet mice	649:661	To identify the proteins involved in the pathogenesis of NAFLD, we also characterized the hepatic proteome in MCD diet mice.
31717261	6	9	theme	hepatic	818:824	arg1	steatosis					826:834	hepatic steatosis	818:834	hepatic steatosis	818:834	As a result of two-dimensional proteomic analysis, it was confirmed that thirteen proteins including antioxidant protein were differentially expressed in hepatic steatosis.
31717261	9	10	theme	O-linked	1081:1088	arg1	modification					1123:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	10	11	theme	ER	1398:1399	arg1	stress					1401:1406	ER stress	1398:1406	ER stress	1398:1406	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	9	12	theme	diet	1220:1223	arg1	mice					1225:1228	MCD diet mice	1216:1228	MCD diet mice	1216:1228	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	2	13	theme	phytopolyphenol	258:272	arg1	pigment					274:280	a natural phytopolyphenol pigment	248:280	a natural phytopolyphenol pigment	248:280	In the present study, we aimed to investigate how curcumin, a natural phytopolyphenol pigment, ameliorates NAFLD.
31717261	2	13	theme	phytopolyphenol	258:272	arg1	curcumin					238:245	curcumin	238:245	curcumin	238:245	In the present study, we aimed to investigate how curcumin, a natural phytopolyphenol pigment, ameliorates NAFLD.
31717261	6	14	theme	analysis	705:712	arg1	result					669:674	a result	667:674	a result of two-dimensional proteomic analysis	667:712	As a result of two-dimensional proteomic analysis, it was confirmed that thirteen proteins including antioxidant protein were differentially expressed in hepatic steatosis.
31717261	6	14	theme	analysis	705:712	arg1	it					715:716	it	715:716	it	715:716	As a result of two-dimensional proteomic analysis, it was confirmed that thirteen proteins including antioxidant protein were differentially expressed in hepatic steatosis.
31717261	9	15	theme	β-N-acetylglucosamine	1090:1110	arg1	modification					1123:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	10	16	theme	biosynthetic	1336:1347	arg1	HBP					1358:1360	HBP	1358:1360	HBP	1358:1360	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	10	16	theme	biosynthetic	1336:1347	arg1	pathway					1349:1355	hexosamine biosynthetic pathway	1325:1355	hexosamine biosynthetic pathway (HBP)	1325:1361	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	10	17	theme	MCD	1289:1291	arg1	diet					1293:1296	the MCD diet	1285:1296	the MCD diet	1285:1296	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	2	18	theme	natural	250:256	arg1	pigment					274:280	a natural phytopolyphenol pigment	248:280	a natural phytopolyphenol pigment	248:280	In the present study, we aimed to investigate how curcumin, a natural phytopolyphenol pigment, ameliorates NAFLD.
31717261	2	18	theme	natural	250:256	arg1	curcumin					238:245	curcumin	238:245	curcumin	238:245	In the present study, we aimed to investigate how curcumin, a natural phytopolyphenol pigment, ameliorates NAFLD.
31717261	6	19	theme	proteomic	695:703	arg1	analysis					705:712	two-dimensional proteomic analysis	679:712	two-dimensional proteomic analysis	679:712	As a result of two-dimensional proteomic analysis, it was confirmed that thirteen proteins including antioxidant protein were differentially expressed in hepatic steatosis.
31717261	4	20	theme	hepatic	480:486	arg1	inflammation					488:499	hepatic inflammation	480:499	hepatic inflammation	480:499	The severity of hepatic inflammation was alleviated by curcumin treatment.
31717261	6	21	theme	two-dimensional	679:693	arg1	analysis					705:712	two-dimensional proteomic analysis	679:712	two-dimensional proteomic analysis	679:712	As a result of two-dimensional proteomic analysis, it was confirmed that thirteen proteins including antioxidant protein were differentially expressed in hepatic steatosis.
31717261	9	22	from	hepatitis	1203:1211	arg1	mice					1225:1228	MCD diet mice	1216:1228	MCD diet mice	1216:1228	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	13	23	theme	steatohepatitis	1809:1823	arg1	mice					1832:1835	non-alcoholic steatohepatitis (NASH) mice	1795:1835	non-alcoholic steatohepatitis (NASH) mice	1795:1835	In conclusion, curcumin inhibits O-GlcNAcylation pathway, leading to antioxidant responses in non-alcoholic steatohepatitis (NASH) mice.
31717261	12	24	theme	SIRT1	1641:1645	arg1	expressions					1592:1602	the expressions	1588:1602	the expressions of superoxide dismutase 1 (SOD1) and SIRT1	1588:1645	Conversely, the expressions of superoxide dismutase 1 (SOD1) and SIRT1 were significantly upregulated by curcumin treatment.
31717261	5	25	theme	hepatic	629:635	arg1	proteome					637:644	the hepatic proteome	625:644	the hepatic proteome in MCD diet mice	625:661	To identify the proteins involved in the pathogenesis of NAFLD, we also characterized the hepatic proteome in MCD diet mice.
31717261	11	26	theme	Curcumin	1409:1416	arg1	treatment					1418:1426	Curcumin treatment	1409:1426	Curcumin treatment	1409:1426	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	11	27	theme	steatosis	1463:1471	arg1	severity					1443:1450	the severity	1439:1450	the severity of hepatic steatosis	1439:1471	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	3	28	theme	hepatic	388:394	arg1	injury					396:401	hepatic injury	388:401	hepatic injury	388:401	Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice.
31717261	0	29	theme	Fatty	34:38	arg1	Disease					46:52	Nonalcoholic Fatty Liver Disease	21:52	Nonalcoholic Fatty Liver Disease	21:52	Curcumin Ameliorates Nonalcoholic Fatty Liver Disease through Inhibition of O-GlcNAcylation.
31717261	11	30	from	dependence	1490:1499	arg1	factor-κB					1531:1539	nuclear factor-κB	1523:1539	nuclear factor-κB (NF-κB) in inflammation signaling	1523:1573	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	11	30	from	dependence	1490:1499	arg1	NF-κB					1542:1546	NF-κB	1542:1546	NF-κB	1542:1546	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	9	31	theme	modification	1123:1134	arg1	regulation					1067:1076	the regulation	1063:1076	the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1063:1134	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	3	32	theme	choline-deficient	429:445	arg1	diet					453:456	choline-deficient (MCD) diet	429:456	choline-deficient (MCD) diet	429:456	Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice.
31717261	3	33	theme	fat	367:369	arg1	accumulation					371:382	fat accumulation	367:382	fat accumulation	367:382	Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice.
31717261	5	34	from	proteome	637:644	arg1	mice					658:661	MCD diet mice	649:661	MCD diet mice	649:661	To identify the proteins involved in the pathogenesis of NAFLD, we also characterized the hepatic proteome in MCD diet mice.
31717261	6	35	theme	antioxidant	765:775	arg1	protein					777:783	antioxidant protein	765:783	antioxidant protein	765:783	As a result of two-dimensional proteomic analysis, it was confirmed that thirteen proteins including antioxidant protein were differentially expressed in hepatic steatosis.
31717261	1	36	theme	progression	106:116	arg1	cause					97:101	The cause	93:101	The cause of progression to non-alcoholic fatty liver disease (NAFLD)	93:161	The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood.
31717261	8	37	theme	O-GlcNAcylation	989:1003	arg1	modification					1005:1016	O-GlcNAcylation modification	989:1016	O-GlcNAcylation modification	989:1016	Interestingly, eight of the identified proteins are known to undergo O-GlcNAcylation modification.
31717261	0	38	theme	Nonalcoholic	21:32	arg1	Disease					46:52	Nonalcoholic Fatty Liver Disease	21:52	Nonalcoholic Fatty Liver Disease	21:52	Curcumin Ameliorates Nonalcoholic Fatty Liver Disease through Inhibition of O-GlcNAcylation.
31717261	11	39	theme	inflammation	1552:1563	arg1	signaling					1565:1573	inflammation signaling	1552:1573	inflammation signaling	1552:1573	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	10	40	theme	O-GlcNAc	1367:1374	arg1	transferase					1376:1386	O-GlcNAc transferase	1367:1386	O-GlcNAc transferase (OGT)	1367:1392	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	10	40	theme	O-GlcNAc	1367:1374	arg1	OGT					1389:1391	OGT	1389:1391	OGT	1389:1391	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	10	41	with	parallel	1234:1241	arg1	inflammation					1271:1282	inflammation	1271:1282	inflammation	1271:1282	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	10	41	with	parallel	1234:1241	arg1	accumulation					1254:1265	lipid accumulation	1248:1265	lipid accumulation	1248:1265	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	12	42	theme	curcumin	1681:1688	arg1	treatment					1690:1698	curcumin treatment	1681:1698	curcumin treatment	1681:1698	Conversely, the expressions of superoxide dismutase 1 (SOD1) and SIRT1 were significantly upregulated by curcumin treatment.
31717261	13	43	theme	antioxidant	1770:1780	arg1	responses					1782:1790	antioxidant responses	1770:1790	antioxidant responses in non-alcoholic steatohepatitis (NASH) mice	1770:1835	In conclusion, curcumin inhibits O-GlcNAcylation pathway, leading to antioxidant responses in non-alcoholic steatohepatitis (NASH) mice.
31717261	10	44	theme	hexosamine	1325:1334	arg1	HBP					1358:1360	HBP	1358:1360	HBP	1358:1360	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	10	44	theme	hexosamine	1325:1334	arg1	pathway					1349:1355	hexosamine biosynthetic pathway	1325:1355	hexosamine biosynthetic pathway (HBP)	1325:1361	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	9	45	link	O-linked	1081:1088	arg1	modification					1123:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	11	46	theme	nuclear	1523:1529	arg1	factor-κB					1531:1539	nuclear factor-κB	1523:1539	nuclear factor-κB (NF-κB) in inflammation signaling	1523:1573	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	11	46	theme	nuclear	1523:1529	arg1	NF-κB					1542:1546	NF-κB	1542:1546	NF-κB	1542:1546	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	0	47	theme	Liver	40:44	arg1	Disease					46:52	Nonalcoholic Fatty Liver Disease	21:52	Nonalcoholic Fatty Liver Disease	21:52	Curcumin Ameliorates Nonalcoholic Fatty Liver Disease through Inhibition of O-GlcNAcylation.
31717261	3	48	theme	methionine	414:423	arg1	mice					458:461	methionine and choline-deficient (MCD) diet mice	414:461	methionine and choline-deficient (MCD) diet mice	414:461	Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice.
31717261	3	49	dep	choline-deficient	429:445	arg1	MCD					448:450	MCD	448:450	MCD	448:450	Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice.
31717261	3	50	theme	diet	453:456	arg1	mice					458:461	methionine and choline-deficient (MCD) diet mice	414:461	methionine and choline-deficient (MCD) diet mice	414:461	Initially, we demonstrated that curcumin dramatically suppresses fat accumulation and hepatic injury induced in methionine and choline-deficient (MCD) diet mice.
31717261	4	51	theme	curcumin	519:526	arg1	treatment					528:536	curcumin treatment	519:536	curcumin treatment	519:536	The severity of hepatic inflammation was alleviated by curcumin treatment.
31717261	1	52	theme	non-alcoholic	121:133	arg1	NAFLD					156:160	NAFLD	156:160	NAFLD	156:160	The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood.
31717261	1	52	theme	non-alcoholic	121:133	arg1	disease					147:153	non-alcoholic fatty liver disease	121:153	non-alcoholic fatty liver disease (NAFLD)	121:161	The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood.
31717261	13	53	theme	non-alcoholic	1795:1807	arg1	NASH					1826:1829	NASH	1826:1829	NASH	1826:1829	In conclusion, curcumin inhibits O-GlcNAcylation pathway, leading to antioxidant responses in non-alcoholic steatohepatitis (NASH) mice.
31717261	13	53	theme	non-alcoholic	1795:1807	arg1	steatohepatitis					1809:1823	non-alcoholic steatohepatitis	1795:1823	non-alcoholic steatohepatitis (NASH) mice	1795:1835	In conclusion, curcumin inhibits O-GlcNAcylation pathway, leading to antioxidant responses in non-alcoholic steatohepatitis (NASH) mice.
31717261	11	54	theme	hepatic	1455:1461	arg1	steatosis					1463:1471	hepatic steatosis	1455:1471	hepatic steatosis	1455:1471	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	8	55	theme	identified	948:957	arg1	proteins					959:966	the identified proteins	944:966	the identified proteins	944:966	Interestingly, eight of the identified proteins are known to undergo O-GlcNAcylation modification.
31717261	1	56	theme	fatty	135:139	arg1	NAFLD					156:160	NAFLD	156:160	NAFLD	156:160	The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood.
31717261	1	56	theme	fatty	135:139	arg1	disease					147:153	non-alcoholic fatty liver disease	121:153	non-alcoholic fatty liver disease (NAFLD)	121:161	The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood.
31717261	2	57	theme	present	195:201	arg1	study					203:207	the present study	191:207	the present study	191:207	In the present study, we aimed to investigate how curcumin, a natural phytopolyphenol pigment, ameliorates NAFLD.
31717261	7	58	from	difference	850:859	arg1	expression					864:873	expression	864:873	expression	864:873	However, the difference in expression was markedly improved by curcumin treatment.
31717261	9	59	theme	MCD	1216:1218	arg1	mice					1225:1228	MCD diet mice	1216:1228	MCD diet mice	1216:1228	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	1	60	theme	liver	141:145	arg1	NAFLD					156:160	NAFLD	156:160	NAFLD	156:160	The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood.
31717261	1	60	theme	liver	141:145	arg1	disease					147:153	non-alcoholic fatty liver disease	121:153	non-alcoholic fatty liver disease (NAFLD)	121:161	The cause of progression to non-alcoholic fatty liver disease (NAFLD) is not fully understood.
31717261	11	61	from	factor-κB	1531:1539	arg1	signaling					1565:1573	inflammation signaling	1552:1573	inflammation signaling	1552:1573	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	9	62	theme	hepatic	1174:1180	arg1	steatosis					1182:1190	hepatic steatosis	1174:1190	hepatic steatosis leading to hepatitis in MCD diet mice	1174:1228	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	9	63	theme	steatosis	1182:1190	arg1	progression					1159:1169	the progression	1155:1169	the progression of hepatic steatosis leading to hepatitis in MCD diet mice	1155:1228	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	11	64	theme	O-GlcNAcylation	1504:1518	arg1	dependence					1490:1499	the dependence	1486:1499	the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling	1486:1573	Curcumin treatment alleviates the severity of hepatic steatosis by relieving the dependence of O-GlcNAcylation on nuclear factor-κB (NF-κB) in inflammation signaling.
31717261	9	65	theme	O-GlcNAc	1113:1120	arg1	modification					1123:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	O-linked β-N-acetylglucosamine (O-GlcNAc) modification	1081:1134	Thus, we further focused on elucidating how the regulation of O-linked β-N-acetylglucosamine (O-GlcNAc) modification is associated with the progression of hepatic steatosis leading to hepatitis in MCD diet mice.
31717261	0	66	theme	O-GlcNAcylation	76:90	arg1	Inhibition					62:71	Inhibition	62:71	Inhibition of O-GlcNAcylation	62:90	Curcumin Ameliorates Nonalcoholic Fatty Liver Disease through Inhibition of O-GlcNAcylation.
31717261	8	67	theme	proteins	959:966	arg1	eight					935:939	eight	935:939	eight	935:939	Interestingly, eight of the identified proteins are known to undergo O-GlcNAcylation modification.
31717261	8	67	theme	proteins	959:966	arg1	proteins					959:966	the identified proteins	944:966	the identified proteins	944:966	Interestingly, eight of the identified proteins are known to undergo O-GlcNAcylation modification.
31717261	10	68	theme	lipid	1248:1252	arg1	accumulation					1254:1265	lipid accumulation	1248:1265	lipid accumulation	1248:1265	In parallel with lipid accumulation and inflammation, the MCD diet significantly up-regulated hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) via ER stress.
31717261	12	69	theme	superoxide	1607:1616	arg1	dismutase					1618:1626	superoxide dismutase 1	1607:1628	superoxide dismutase 1 (SOD1)	1607:1635	Conversely, the expressions of superoxide dismutase 1 (SOD1) and SIRT1 were significantly upregulated by curcumin treatment.
31717261	12	69	theme	superoxide	1607:1616	arg1	SOD1					1631:1634	SOD1	1631:1634	SOD1	1631:1634	Conversely, the expressions of superoxide dismutase 1 (SOD1) and SIRT1 were significantly upregulated by curcumin treatment.
31717261	12	70	theme	dismutase	1618:1626	arg1	expressions					1592:1602	the expressions	1588:1602	the expressions of superoxide dismutase 1 (SOD1) and SIRT1	1588:1645	Conversely, the expressions of superoxide dismutase 1 (SOD1) and SIRT1 were significantly upregulated by curcumin treatment.
31498587	8	0	from	challenge	1172:1180	arg1	model					1203:1207	a lung metastasis model	1185:1207	a lung metastasis model	1185:1207	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	8	1	theme	significant	1216:1226	arg1	reductions					1228:1237	significant reductions	1216:1237	significant reductions of the number of tumor foci in the lungs of immunized mice	1216:1296	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	10	2	theme	anticancer	1499:1508	arg1	potential					1486:1494	great potential	1480:1494	great potential	1480:1494	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	10	2	theme	anticancer	1499:1508	arg1	vaccines					1510:1517	anticancer vaccines	1499:1517	anticancer vaccines	1499:1517	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	3	3	theme	Tf	507:508	arg1	antigen					522:528	the Tf and the STn antigen	503:528	the Tf and the STn antigen	503:528	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	1	4	theme	anticancer	179:188	arg1	vaccines					190:197	anticancer vaccines	179:197	anticancer vaccines	179:197	Mucin-1 (MUC1) is a highly attractive antigenic target for anticancer vaccines.
31498587	8	5	theme	tumor	1166:1170	arg1	challenge					1172:1180	tumor challenge	1166:1180	tumor challenge in a lung metastasis model	1166:1207	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	8	6	theme	number	1246:1251	arg1	reductions					1228:1237	significant reductions	1216:1237	significant reductions of the number of tumor foci in the lungs of immunized mice	1216:1296	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	7	7	theme	melanoma	1050:1057	arg1	cells					1068:1072	MUC1-expressing melanoma B16-MUC1 cells	1034:1072	MUC1-expressing melanoma B16-MUC1 cells	1034:1072	Antibodies induced by Qβ-MUC1-Tf showed strongest binding, with MUC1-expressing melanoma B16-MUC1 cells, and effectively killed these cells in vitro.
31498587	5	8	theme	superior	793:800	arg1	levels					802:807	superior levels	793:807	superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units	793:877	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	8	9	theme	lung	1187:1190	arg1	model					1203:1207	a lung metastasis model	1185:1207	a lung metastasis model	1185:1207	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	6	10	theme	wide	912:915	arg1	range					917:921	a wide range	910:921	a wide range of MUC1 glycopeptides bearing diverse glycans	910:967	The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans.
31498587	4	11	theme	powerful	602:609	arg1	carrier					589:595	The bacteriophage Qβ carrier	568:595	The bacteriophage Qβ carrier	568:595	The bacteriophage Qβ carrier is a powerful carrier for antigen delivery.
31498587	4	11	theme	powerful	602:609	arg1	carrier					611:617	a powerful carrier	600:617	a powerful carrier for antigen delivery	600:638	The bacteriophage Qβ carrier is a powerful carrier for antigen delivery.
31498587	5	12	theme	glycopeptides	676:688	arg1	conjugates					645:654	The conjugates	641:654	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ	641:696	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	9	13	theme	tumor	1421:1425	arg1	model					1427:1431	a tumor model	1419:1431	a tumor model	1419:1431	This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model.
31498587	2	14	dep	antigen	312:318	arg1	the					282:284	the	282:284	the	282:284	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	6	15	theme	IgG	884:886	arg1	antibodies					888:897	The IgG antibodies	880:897	The IgG antibodies	880:897	The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans.
31498587	5	16	gly	glycopeptides	676:688	arg2	glycopeptides					676:688	MUC1-Tf and -STn glycopeptides	659:688	MUC1-Tf and -STn glycopeptides	659:688	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	8	17	theme	immunized	1283:1291	arg1	mice					1293:1296	immunized mice	1283:1296	immunized mice	1283:1296	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	0	18	theme	Glycopeptide	69:80	arg1	Conjugates					82:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	2	19	theme	O-linked	254:261	arg1	glycans					263:269	O-linked glycans	254:269	O-linked glycans	254:269	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	1	20	theme	attractive	147:156	arg1	Mucin-1					120:126	Mucin-1	120:126	Mucin-1 (MUC1)	120:133	Mucin-1 (MUC1) is a highly attractive antigenic target for anticancer vaccines.
31498587	1	20	theme	attractive	147:156	arg1	target					168:173	a highly attractive antigenic target	138:173	a highly attractive antigenic target for anticancer vaccines	138:197	Mucin-1 (MUC1) is a highly attractive antigenic target for anticancer vaccines.
31498587	5	21	theme	human	740:744	arg1	mice					772:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	6	22	theme	diverse	953:959	arg1	glycans					961:967	diverse glycans	953:967	diverse glycans	953:967	The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans.
31498587	6	23	theme	glycopeptides	931:943	arg1	range					917:921	a wide range	910:921	a wide range of MUC1 glycopeptides bearing diverse glycans	910:967	The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans.
31498587	3	24	theme	MUC1	434:437	arg1	glycopeptides					439:451	MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site)	434:493	MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site)	434:493	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	0	25	theme	Disaccharide	42:53	arg1	Conjugates					82:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	0	26	theme	Immunological	14:26	arg1	Evaluation					28:37	Immunological Evaluation	14:37	Immunological Evaluation	14:37	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	3	27	theme	potential	403:411	arg1	vaccines					424:431	potential anticancer vaccines	403:431	potential anticancer vaccines	403:431	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	3	27	theme	potential	403:411	arg1	antigens					391:398	these antigens	385:398	these antigens	385:398	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	9	28	dep	in	1399:1400	arg1	vivo					1402:1405	vivo	1402:1405	vivo	1402:1405	This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model.
31498587	3	29	theme	SAPDT	453:457	arg1	RPAP					459:462	SAPDT*RPAP	453:462	MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site)	434:493	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	5	30	theme	transgenic	751:760	arg1	mice					772:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	5	31	with	antibodies	826:835	arg1	titers					842:847	titers	842:847	titers reaching over 2 million units	842:877	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	2	32	theme	STn	352:354	arg1	antigen					357:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	5	33	theme	MUC1.Tg	763:769	arg1	mice					772:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	3	34	dep	glycopeptides	439:451	arg1	RPAP					459:462	SAPDT*RPAP	453:462	MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site)	434:493	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	10	35	theme	Qβ-MUC1	1443:1449	arg1	conjugates					1464:1473	Qβ-MUC1 glycopeptide conjugates	1443:1473	Qβ-MUC1 glycopeptide conjugates	1443:1473	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	3	36	gly	glycopeptides	439:451	arg2	glycopeptides					439:451	MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site)	434:493	MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site)	434:493	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	0	37	with	Synthesis	0:8	arg1	Particles					109:117	Virus-like Particles	98:117	Virus-like Particles	98:117	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	2	38	theme	Thomsen-nouveau	335:349	arg1	antigen					357:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	39	contain	contain	228:234	arg2	antigen					312:318	Thomsen-Friedenreich (Tf) antigen	286:318	Thomsen-Friedenreich (Tf) antigen	286:318	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	39	contain	contain	228:234	arg1	MUC1					219:222	Naturally existing MUC1	200:222	Naturally existing MUC1	200:222	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	39	contain	contain	228:234	arg2	antigen					357:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	39	contain	contain	228:234	arg2	types					245:249	multiple types	236:249	multiple types	236:249	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	5	40	theme	IgG	822:824	arg1	antibodies					826:835	anti-MUC1 IgG antibodies	812:835	anti-MUC1 IgG antibodies with titers reaching over 2 million units	812:877	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	9	41	theme	first	1349:1353	arg1	time					1355:1358	the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model	1345:1431	the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model	1345:1431	This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model.
31498587	9	41	theme	first	1349:1353	arg1	This					1336:1339	This	1336:1339	This	1336:1339	This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model.
31498587	4	42	theme	bacteriophage	572:584	arg1	carrier					589:595	The bacteriophage Qβ carrier	568:595	The bacteriophage Qβ carrier	568:595	The bacteriophage Qβ carrier is a powerful carrier for antigen delivery.
31498587	4	42	theme	bacteriophage	572:584	arg1	carrier					611:617	a powerful carrier	600:617	a powerful carrier for antigen delivery	600:638	The bacteriophage Qβ carrier is a powerful carrier for antigen delivery.
31498587	10	43	theme	great	1480:1484	arg1	potential					1486:1494	great potential	1480:1494	great potential	1480:1494	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	10	43	theme	great	1480:1484	arg1	vaccines					1510:1517	anticancer vaccines	1499:1517	anticancer vaccines	1499:1517	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	5	44	theme	immune-tolerant	724:738	arg1	mice					772:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	3	45	theme	glycosylation	475:487	arg1	site					489:492	the glycosylation site	471:492	the glycosylation site	471:492	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	3	45	theme	glycosylation	475:487	arg1	*					466:466	T*	465:466	T*	465:466	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	2	46	theme	Tf	308:309	arg1	antigen					312:318	Thomsen-Friedenreich (Tf) antigen	286:318	Thomsen-Friedenreich (Tf) antigen	286:318	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	9	47	theme	MUC1-Tf-based	1367:1379	arg1	vaccine					1381:1387	a MUC1-Tf-based vaccine	1365:1387	a MUC1-Tf-based vaccine	1365:1387	This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model.
31498587	10	48	gly	glycopeptide	1451:1462	arg2	glycopeptide					1451:1462	Qβ-MUC1 glycopeptide conjugates	1443:1473	Qβ-MUC1 glycopeptide conjugates	1443:1473	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	2	49	theme	Thomsen-Friedenreich	286:305	arg1	antigen					312:318	Thomsen-Friedenreich (Tf) antigen	286:318	Thomsen-Friedenreich (Tf) antigen	286:318	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	5	50	theme	antibodies	826:835	arg1	levels					802:807	superior levels	793:807	superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units	793:877	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	5	51	theme	anti-MUC1	812:820	arg1	antibodies					826:835	anti-MUC1 IgG antibodies	812:835	anti-MUC1 IgG antibodies with titers reaching over 2 million units	812:877	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	0	52	theme	Bearing	55:61	arg1	Conjugates					82:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	7	53	theme	B16-MUC1	1059:1066	arg1	cells					1068:1072	MUC1-expressing melanoma B16-MUC1 cells	1034:1072	MUC1-expressing melanoma B16-MUC1 cells	1034:1072	Antibodies induced by Qβ-MUC1-Tf showed strongest binding, with MUC1-expressing melanoma B16-MUC1 cells, and effectively killed these cells in vitro.
31498587	9	54	theme	in	1399:1400	arg1	efficacy					1407:1414	in vivo efficacy	1399:1414	in vivo efficacy	1399:1414	This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model.
31498587	6	55	theme	MUC1	926:929	arg1	glycopeptides					931:943	MUC1 glycopeptides	926:943	MUC1 glycopeptides bearing diverse glycans	926:967	The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans.
31498587	4	56	theme	antigen	623:629	arg1	delivery					631:638	antigen delivery	623:638	antigen delivery	623:638	The bacteriophage Qβ carrier is a powerful carrier for antigen delivery.
31498587	5	57	theme	MUC1-Tf	659:665	arg1	glycopeptides					676:688	MUC1-Tf and -STn glycopeptides	659:688	MUC1-Tf and -STn glycopeptides	659:688	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	3	58	theme	STn	518:520	arg1	antigen					522:528	the Tf and the STn antigen	503:528	the Tf and the STn antigen	503:528	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	5	59	theme	-STn	671:674	arg1	glycopeptides					676:688	MUC1-Tf and -STn glycopeptides	659:688	MUC1-Tf and -STn glycopeptides	659:688	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	7	60	theme	strongest	1010:1018	arg1	binding					1020:1026	strongest binding	1010:1026	strongest binding	1010:1026	Antibodies induced by Qβ-MUC1-Tf showed strongest binding, with MUC1-expressing melanoma B16-MUC1 cells, and effectively killed these cells in vitro.
31498587	2	61	theme	multiple	236:243	arg1	types					245:249	multiple types	236:249	multiple types	236:249	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	61	theme	multiple	236:243	arg1	antigen					312:318	Thomsen-Friedenreich (Tf) antigen	286:318	Thomsen-Friedenreich (Tf) antigen	286:318	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	61	theme	multiple	236:243	arg1	antigen					357:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	8	62	from	reductions	1228:1237	arg1	lungs					1274:1278	the lungs	1270:1278	the lungs of immunized mice	1270:1296	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	5	63	theme	million	865:871	arg1	units					873:877	2 million units	863:877	2 million units	863:877	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	8	64	theme	metastasis	1192:1201	arg1	model					1203:1207	a lung metastasis model	1185:1207	a lung metastasis model	1185:1207	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	7	65	theme	MUC1-expressing	1034:1048	arg1	cells					1068:1072	MUC1-expressing melanoma B16-MUC1 cells	1034:1072	MUC1-expressing melanoma B16-MUC1 cells	1034:1072	Antibodies induced by Qβ-MUC1-Tf showed strongest binding, with MUC1-expressing melanoma B16-MUC1 cells, and effectively killed these cells in vitro.
31498587	8	66	theme	foci	1262:1265	arg1	number					1246:1251	the number	1242:1251	the number of tumor foci	1242:1265	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	3	67	theme	T	465:465	arg1	site					489:492	the glycosylation site	471:492	the glycosylation site	471:492	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	3	67	theme	T	465:465	arg1	*					466:466	T*	465:466	T*	465:466	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	0	68	theme	Conjugates	82:91	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis	0:8	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	0	68	theme	Conjugates	82:91	arg1	Evaluation					28:37	Immunological Evaluation	14:37	Immunological Evaluation	14:37	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	2	69	theme	glycans	263:269	arg1	types					245:249	multiple types	236:249	multiple types	236:249	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	69	theme	glycans	263:269	arg1	antigen					312:318	Thomsen-Friedenreich (Tf) antigen	286:318	Thomsen-Friedenreich (Tf) antigen	286:318	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	69	theme	glycans	263:269	arg1	antigen					357:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	0	70	theme	Virus-like	98:107	arg1	Particles					109:117	Virus-like Particles	98:117	Virus-like Particles	98:117	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	5	71	used	utilized	703:710	arg2	conjugates					645:654	The conjugates	641:654	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ	641:696	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	1	72	theme	antigenic	158:166	arg1	Mucin-1					120:126	Mucin-1	120:126	Mucin-1 (MUC1)	120:133	Mucin-1 (MUC1) is a highly attractive antigenic target for anticancer vaccines.
31498587	1	72	theme	antigenic	158:166	arg1	target					168:173	a highly attractive antigenic target	138:173	a highly attractive antigenic target for anticancer vaccines	138:197	Mucin-1 (MUC1) is a highly attractive antigenic target for anticancer vaccines.
31498587	8	73	with	Vaccination	1120:1130	arg1	Qβ-MUC1-Tf					1137:1146	Qβ-MUC1-Tf	1137:1146	Qβ-MUC1-Tf	1137:1146	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	8	74	theme	mice	1293:1296	arg1	lungs					1274:1278	the lungs	1270:1278	the lungs of immunized mice	1270:1296	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	2	75	link	O-linked	254:261	arg1	glycans					263:269	O-linked glycans	254:269	O-linked glycans	254:269	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	10	76	contain	have	1475:1478	arg2	vaccines					1510:1517	anticancer vaccines	1499:1517	anticancer vaccines	1499:1517	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	10	76	contain	have	1475:1478	arg2	potential					1486:1494	great potential	1480:1494	great potential	1480:1494	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	10	76	contain	have	1475:1478	arg1	conjugates					1464:1473	Qβ-MUC1 glycopeptide conjugates	1443:1473	Qβ-MUC1 glycopeptide conjugates	1443:1473	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	5	77	with	conjugates	645:654	arg1	Qβ					695:696	Qβ	695:696	Qβ	695:696	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	3	78	gly	glycosylation	475:487	arg2	site					489:492	the glycosylation site	471:492	the glycosylation site	471:492	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	3	78	gly	glycosylation	475:487	arg2	*					466:466	T*	465:466	T*	465:466	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	8	79	theme	control	1322:1328	arg1	mice					1330:1333	control mice	1322:1333	control mice	1322:1333	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	5	80	theme	MUC1	746:749	arg1	mice					772:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	immune-tolerant human MUC1 transgenic (MUC1.Tg) mice	724:775	The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units.
31498587	8	81	theme	tumor	1256:1260	arg1	foci					1262:1265	tumor foci	1256:1265	tumor foci	1256:1265	Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice.
31498587	3	82	theme	anticancer	413:422	arg1	vaccines					424:431	potential anticancer vaccines	403:431	potential anticancer vaccines	403:431	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	3	82	theme	anticancer	413:422	arg1	antigens					391:398	these antigens	385:398	these antigens	385:398	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	0	83	with	Evaluation	28:37	arg1	Particles					109:117	Virus-like Particles	98:117	Virus-like Particles	98:117	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	3	84	theme	*	458:458	arg1	RPAP					459:462	SAPDT*RPAP	453:462	MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site)	434:493	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	0	85	theme	MUC-1	63:67	arg1	Conjugates					82:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Disaccharide Bearing MUC-1 Glycopeptide Conjugates	42:91	Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles.
31498587	10	86	theme	glycopeptide	1451:1462	arg1	conjugates					1464:1473	Qβ-MUC1 glycopeptide conjugates	1443:1473	Qβ-MUC1 glycopeptide conjugates	1443:1473	As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
31498587	6	87	gly	glycopeptides	931:943	arg2	glycopeptides					931:943	MUC1 glycopeptides	926:943	MUC1 glycopeptides bearing diverse glycans	926:967	The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans.
31498587	2	88	theme	existing	210:217	arg1	MUC1					219:222	Naturally existing MUC1	200:222	Naturally existing MUC1	200:222	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	2	89	theme	Sialyl	328:333	arg1	antigen					357:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	the Sialyl Thomsen-nouveau (STn) antigen	324:363	Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen-Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen.
31498587	3	90	dep	RPAP	459:462	arg1	site					489:492	the glycosylation site	471:492	the glycosylation site	471:492	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	3	90	dep	RPAP	459:462	arg1	*					466:466	T*	465:466	T*	465:466	In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized.
31498587	4	91	theme	Qβ	586:587	arg1	carrier					589:595	The bacteriophage Qβ carrier	568:595	The bacteriophage Qβ carrier	568:595	The bacteriophage Qβ carrier is a powerful carrier for antigen delivery.
31498587	4	91	theme	Qβ	586:587	arg1	carrier					611:617	a powerful carrier	600:617	a powerful carrier for antigen delivery	600:638	The bacteriophage Qβ carrier is a powerful carrier for antigen delivery.
30865517	4	0	with	O-GlcNAcase	797:807	arg1	Thiamet-G					814:822	Thiamet-G	814:822	Thiamet-G	814:822	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	6	1	theme	subunit	1262:1268	arg1	proteins					1270:1277	complex subunit proteins	1254:1277	complex subunit proteins	1254:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	3	2	theme	dose-dependent	616:629	arg1	changes					631:637	temporal and dose-dependent changes	603:637	temporal and dose-dependent changes in O-GlcNAcylation	603:656	This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function.
30865517	4	3	theme	O-GlcNAc	767:774	arg1	levels					776:781	O-GlcNAc levels	767:781	O-GlcNAc levels	767:781	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	3	4	theme	different	667:675	arg1	effects					677:683	different effects	667:683	different effects	667:683	This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function.
30865517	6	5	theme	O-GlcNAc	1229:1236	arg1	modification					1238:1249	direct increased O-GlcNAc modification	1212:1249	direct increased O-GlcNAc modification of complex subunit proteins	1212:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	9	6	theme	impaired	1777:1784	arg1	bioenergetics					1786:1798	impaired bioenergetics	1777:1798	impaired bioenergetics associated with short-term increases in O-GlcNAc levels	1777:1854	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	9	7	dep	impaired	1872:1879	arg1	mitochondrial					1899:1911	mitochondrial	1899:1911	mitochondrial	1899:1911	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	9	7	dep	impaired	1872:1879	arg1	LonP1-dependent					1882:1896	LonP1-dependent	1882:1896	LonP1-dependent	1882:1896	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	2	8	with	stress	519:524	arg1	effects					575:581	detrimental effects	563:581	detrimental effects	563:581	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	2	8	with	stress	519:524	arg1	beneficial					548:557	beneficial	548:557	beneficial	548:557	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	9	9	theme	short-term	1816:1825	arg1	increases					1827:1835	short-term increases	1816:1835	short-term increases in O-GlcNAc levels	1816:1854	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	7	10	theme	protein	1449:1455	arg1	levels					1457:1462	p62 protein levels	1445:1462	p62 protein levels	1445:1462	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	9	11	from	increases	1827:1835	arg1	levels					1849:1854	O-GlcNAc levels	1840:1854	O-GlcNAc levels	1840:1854	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	6	12	mod	modification	1238:1249	arg3	O-GlcNAc					1229:1236	direct increased O-GlcNAc modification	1212:1249	direct increased O-GlcNAc modification of complex subunit proteins	1212:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	6	12	mod	modification	1238:1249	arg1	proteins					1270:1277	complex subunit proteins	1254:1277	complex subunit proteins	1254:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	1	13	theme	β-N-acetylglucosamine	181:201	arg1	attachment					158:167	The attachment	154:167	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments	154:295	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	13	theme	β-N-acetylglucosamine	181:201	arg1	mechanism					340:348	an important mechanism	327:348	an important mechanism regulating cellular function	327:377	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	2	14	theme	detrimental	563:573	arg1	effects					575:581	detrimental effects	563:581	detrimental effects	563:581	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	4	15	from	decrease	867:874	arg1	bioenergetics					888:900	cellular bioenergetics	879:900	cellular bioenergetics	879:900	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	5	16	theme	mitochondrial	988:1000	arg1	number					1002:1007	mitochondrial number	988:1007	mitochondrial number	988:1007	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	0	17	theme	mitochondrial	114:126	arg1	turnover					144:151	LonP1-mediated mitochondrial protein complex turnover	99:151	LonP1-mediated mitochondrial protein complex turnover	99:151	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	5	18	theme	protein	1051:1057	arg1	levels					1059:1064	the protein levels	1047:1064	the protein levels of the subunits of several electron transport complex proteins	1047:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	8	19	theme	Lon	1620:1622	arg1	homolog					1633:1639	the mitochondrial Lon protease homolog 1	1602:1641	the mitochondrial Lon protease homolog 1 (LonP1)	1602:1649	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	8	19	theme	Lon	1620:1622	arg1	LonP1					1644:1648	LonP1	1644:1648	LonP1	1644:1648	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	0	20	theme	complex	136:142	arg1	turnover					144:151	LonP1-mediated mitochondrial protein complex turnover	99:151	LonP1-mediated mitochondrial protein complex turnover	99:151	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	6	21	theme	observed	1156:1163	arg1	changes					1178:1184	the observed bioenergetic changes	1152:1184	the observed bioenergetic changes	1152:1184	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	8	22	theme	homolog	1633:1639	arg1	levels					1592:1597	the protein levels	1580:1597	the protein levels of the mitochondrial Lon protease homolog 1 (LonP1)	1580:1649	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	0	23	theme	Acute	0:4	arg1	increases					6:14	Acute increases	0:14	Acute increases in O-GlcNAc	0:26	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	1	24	theme	important	330:338	arg1	attachment					158:167	The attachment	154:167	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments	154:295	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	24	theme	important	330:338	arg1	mechanism					340:348	an important mechanism	327:348	an important mechanism regulating cellular function	327:377	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	9	25	theme	complex	1913:1919	arg1	turnover					1929:1936	impaired, LonP1-dependent, mitochondrial complex protein turnover	1872:1936	impaired, LonP1-dependent, mitochondrial complex protein turnover	1872:1936	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	3	26	contain	have	662:665	arg1	changes					631:637	temporal and dose-dependent changes	603:637	temporal and dose-dependent changes in O-GlcNAcylation	603:656	This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function.
30865517	3	26	contain	have	662:665	arg2	effects					677:683	different effects	667:683	different effects	667:683	This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function.
30865517	1	27	link	O-linked	172:179	arg1	β-N-acetylglucosamine					181:201	O-linked β-N-acetylglucosamine	172:201	O-linked β-N-acetylglucosamine (O-GlcNAc)	172:212	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	27	link	O-linked	172:179	arg1	O-GlcNAc					204:211	O-GlcNAc	204:211	O-GlcNAc	204:211	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	4	28	theme	mitochondrial	916:928	arg1	I					938:938	mitochondrial complex I	916:938	mitochondrial complex I	916:938	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	2	29	theme	potential	470:478	arg1	mechanism					480:488	a potential mechanism	468:488	a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects	468:581	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	2	29	theme	potential	470:478	arg1	modification					406:417	the O-GlcNAc modification	393:417	the O-GlcNAc modification of mitochondrial proteins	393:443	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	5	30	theme	transport	1102:1110	arg1	proteins					1120:1127	several electron transport complex proteins	1085:1127	several electron transport complex proteins	1085:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	2	31	theme	O-GlcNAc	397:404	arg1	mechanism					480:488	a potential mechanism	468:488	a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects	468:581	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	2	31	theme	O-GlcNAc	397:404	arg1	modification					406:417	the O-GlcNAc modification	393:417	the O-GlcNAc modification of mitochondrial proteins	393:443	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	0	32	theme	mitochondrial	46:58	arg1	bioenergetics					60:72	mitochondrial bioenergetics	46:72	mitochondrial bioenergetics	46:72	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	5	33	theme	proteins	1120:1127	arg1	subunits					1073:1080	the subunits	1069:1080	the subunits of several electron transport complex proteins	1069:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	4	34	theme	cellular	879:886	arg1	bioenergetics					888:900	cellular bioenergetics	879:900	cellular bioenergetics	879:900	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	1	35	theme	proteins	254:261	arg1	threonine					232:240	threonine	232:240	threonine	232:240	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	35	theme	proteins	254:261	arg1	serine					221:226	serine	221:226	serine	221:226	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	5	36	theme	subunits	1073:1080	arg1	levels					1059:1064	the protein levels	1047:1064	the protein levels of the subunits of several electron transport complex proteins	1047:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	2	37	theme	proteins	436:443	arg1	mechanism					480:488	a potential mechanism	468:488	a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects	468:581	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	2	37	theme	proteins	436:443	arg1	modification					406:417	the O-GlcNAc modification	393:417	the O-GlcNAc modification of mitochondrial proteins	393:443	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	8	38	theme	other	1723:1727	arg1	proteins					1743:1750	other mitochondrial proteins	1723:1750	other mitochondrial proteins	1723:1750	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	1	39	theme	distinct	266:273	arg1	compartments					284:295	distinct cellular compartments	266:295	distinct cellular compartments	266:295	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	5	40	theme	several	1085:1091	arg1	proteins					1120:1127	several electron transport complex proteins	1085:1127	several electron transport complex proteins	1085:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	7	41	theme	ubiquitinated	1361:1373	arg1	proteins					1375:1382	mitochondrial ubiquitinated proteins	1347:1382	mitochondrial ubiquitinated proteins	1347:1382	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	8	42	theme	IV	1685:1686	arg1	subunits					1688:1695	complex IV subunits	1677:1695	complex IV subunits	1677:1695	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	4	43	theme	IV	949:950	arg1	activities					952:961	IV activities	949:961	IV activities	949:961	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	1	44	attach	attachment	158:167	arg2	O-GlcNAc					204:211	O-GlcNAc	204:211	O-GlcNAc	204:211	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	44	attach	attachment	158:167	arg1	threonine					232:240	threonine	232:240	threonine	232:240	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	44	attach	attachment	158:167	arg2	β-N-acetylglucosamine					181:201	O-linked β-N-acetylglucosamine	172:201	O-linked β-N-acetylglucosamine (O-GlcNAc)	172:212	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	44	attach	attachment	158:167	arg1	serine					221:226	serine	221:226	serine	221:226	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	6	45	theme	proteins	1270:1277	arg1	modification					1238:1249	direct increased O-GlcNAc modification	1212:1249	direct increased O-GlcNAc modification of complex subunit proteins	1212:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	6	46	theme	complex	1254:1260	arg1	proteins					1270:1277	complex subunit proteins	1254:1277	complex subunit proteins	1254:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	8	47	theme	mitochondrial	1606:1618	arg1	homolog					1633:1639	the mitochondrial Lon protease homolog 1	1602:1641	the mitochondrial Lon protease homolog 1 (LonP1)	1602:1649	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	8	47	theme	mitochondrial	1606:1618	arg1	LonP1					1644:1648	LonP1	1644:1648	LonP1	1644:1648	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	7	48	from	Increases	1280:1288	arg1	O-GlcNAc					1293:1300	O-GlcNAc	1293:1300	O-GlcNAc	1293:1300	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	6	49	theme	increased	1219:1227	arg1	modification					1238:1249	direct increased O-GlcNAc modification	1212:1249	direct increased O-GlcNAc modification of complex subunit proteins	1212:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	3	50	theme	mitochondrial	688:700	arg1	function					702:709	mitochondrial function	688:709	mitochondrial function	688:709	This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function.
30865517	8	51	from	increase	1518:1525	arg1	levels					1539:1544	O-GlcNAc levels	1530:1544	O-GlcNAc levels	1530:1544	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	1	52	from	threonine	232:240	arg1	compartments					284:295	distinct cellular compartments	266:295	distinct cellular compartments	266:295	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	4	53	dep	6	834:834	arg1	to					831:832	to	831:832	to	831:832	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	8	54	theme	protein	1584:1590	arg1	levels					1592:1597	the protein levels	1580:1597	the protein levels of the mitochondrial Lon protease homolog 1 (LonP1)	1580:1649	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	1	55	from	serine	221:226	arg1	compartments					284:295	distinct cellular compartments	266:295	distinct cellular compartments	266:295	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	56	theme	O-linked	172:179	arg1	β-N-acetylglucosamine					181:201	O-linked β-N-acetylglucosamine	172:201	O-linked β-N-acetylglucosamine (O-GlcNAc)	172:212	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	56	theme	O-linked	172:179	arg1	O-GlcNAc					204:211	O-GlcNAc	204:211	O-GlcNAc	204:211	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	9	57	theme	O-GlcNAc	1840:1847	arg1	levels					1849:1854	O-GlcNAc levels	1840:1854	O-GlcNAc levels	1840:1854	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	7	58	theme	p62	1445:1447	arg1	levels					1457:1462	p62 protein levels	1445:1462	p62 protein levels	1445:1462	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	0	59	theme	LonP1-mediated	99:112	arg1	turnover					144:151	LonP1-mediated mitochondrial protein complex turnover	99:151	LonP1-mediated mitochondrial protein complex turnover	99:151	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	0	60	from	increases	6:14	arg1	O-GlcNAc					19:26	O-GlcNAc	19:26	O-GlcNAc	19:26	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	3	61	from	changes	631:637	arg1	O-GlcNAcylation					642:656	O-GlcNAcylation	642:656	O-GlcNAcylation	642:656	This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function.
30865517	0	62	theme	protein	128:134	arg1	turnover					144:151	LonP1-mediated mitochondrial protein complex turnover	99:151	LonP1-mediated mitochondrial protein complex turnover	99:151	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	8	63	theme	protease	1624:1631	arg1	homolog					1633:1639	the mitochondrial Lon protease homolog 1	1602:1641	the mitochondrial Lon protease homolog 1 (LonP1)	1602:1649	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	8	63	theme	protease	1624:1631	arg1	LonP1					1644:1648	LonP1	1644:1648	LonP1	1644:1648	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	0	64	theme	turnover	144:151	arg1	dysregulation					82:94	dysregulation	82:94	dysregulation of LonP1-mediated mitochondrial protein complex turnover	82:151	Acute increases in O-GlcNAc indirectly impair mitochondrial bioenergetics through dysregulation of LonP1-mediated mitochondrial protein complex turnover.
30865517	7	65	dep	phosphatase	1385:1395	arg1	kinase					1424:1429	induced kinase 1	1416:1431	induced kinase 1	1416:1431	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	6	66	theme	bioenergetic	1165:1176	arg1	changes					1178:1184	the observed bioenergetic changes	1152:1184	the observed bioenergetic changes	1152:1184	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	9	67	theme	impaired	1872:1879	arg1	turnover					1929:1936	impaired, LonP1-dependent, mitochondrial complex protein turnover	1872:1936	impaired, LonP1-dependent, mitochondrial complex protein turnover	1872:1936	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	4	68	theme	time-dependent	852:865	arg1	decrease					867:874	a time-dependent decrease	850:874	a time-dependent decrease in cellular bioenergetics	850:900	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	7	69	theme	induced	1416:1422	arg1	kinase					1424:1429	induced kinase 1	1416:1431	induced kinase 1	1416:1431	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	5	70	theme	electron	1093:1100	arg1	proteins					1120:1127	several electron transport complex proteins	1085:1127	several electron transport complex proteins	1085:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	7	71	theme	tensin	1401:1406	arg1	homolog					1408:1414	tensin homolog	1401:1414	tensin homolog	1401:1414	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	9	72	theme	protein	1921:1927	arg1	turnover					1929:1936	impaired, LonP1-dependent, mitochondrial complex protein turnover	1872:1936	impaired, LonP1-dependent, mitochondrial complex protein turnover	1872:1936	These data suggest that impaired bioenergetics associated with short-term increases in O-GlcNAc levels could be due to impaired, LonP1-dependent, mitochondrial complex protein turnover.
30865517	1	73	dep	serine	221:226	arg1	the					217:219	the	217:219	the	217:219	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	1	73	dep	serine	221:226	arg1	residues					242:249	residues	242:249	residues	242:249	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	8	74	from	decrease	1568:1575	arg1	levels					1592:1597	the protein levels	1580:1597	the protein levels of the mitochondrial Lon protease homolog 1 (LonP1)	1580:1649	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	1	75	theme	cellular	361:368	arg1	function					370:377	cellular function	361:377	cellular function	361:377	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
30865517	5	76	theme	complex	1112:1118	arg1	proteins					1120:1127	several electron transport complex proteins	1085:1127	several electron transport complex proteins	1085:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	6	77	theme	direct	1212:1217	arg1	modification					1238:1249	direct increased O-GlcNAc modification	1212:1249	direct increased O-GlcNAc modification of complex subunit proteins	1212:1277	However, the observed bioenergetic changes appeared not to be due to direct increased O-GlcNAc modification of complex subunit proteins.
30865517	4	78	theme	complex	930:936	arg1	I					938:938	mitochondrial complex I	916:938	mitochondrial complex I	916:938	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	5	79	from	increase	1035:1042	arg1	levels					1059:1064	the protein levels	1047:1064	the protein levels of the subunits of several electron transport complex proteins	1047:1127	Under these conditions, mitochondrial number was unchanged, whereas an increase in the protein levels of the subunits of several electron transport complex proteins was observed.
30865517	7	80	theme	proteins	1375:1382	arg1	accumulation					1331:1342	an accumulation	1328:1342	an accumulation of mitochondrial ubiquitinated proteins	1328:1382	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	8	81	theme	complex	1677:1683	arg1	subunits					1688:1695	complex IV subunits	1677:1695	complex IV subunits	1677:1695	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	2	82	theme	mitochondrial	422:434	arg1	proteins					436:443	mitochondrial proteins	422:443	mitochondrial proteins	422:443	Importantly, the O-GlcNAc modification of mitochondrial proteins has been identified as a potential mechanism to modulate metabolism under stress with both potentially beneficial and detrimental effects.
30865517	8	83	theme	mitochondrial	1729:1741	arg1	proteins					1743:1750	other mitochondrial proteins	1723:1750	other mitochondrial proteins	1723:1750	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	7	84	theme	mitochondrial	1347:1359	arg1	proteins					1375:1382	mitochondrial ubiquitinated proteins	1347:1382	mitochondrial ubiquitinated proteins	1347:1382	Increases in O-GlcNAc were also associated with an accumulation of mitochondrial ubiquitinated proteins; phosphatase and tensin homolog induced kinase 1 (PINK1) and p62 protein levels were also significantly increased.
30865517	4	85	theme	current	719:725	arg1	study					727:731	the current study	715:731	the current study	715:731	In the current study, we found that acutely augmenting O-GlcNAc levels by inhibiting O-GlcNAcase with Thiamet-G for up to 6 h resulted in a time-dependent decrease in cellular bioenergetics and decreased mitochondrial complex I, II, and IV activities.
30865517	8	86	theme	O-GlcNAc	1530:1537	arg1	levels					1539:1544	O-GlcNAc levels	1530:1544	O-GlcNAc levels	1530:1544	Interestingly, the increase in O-GlcNAc levels was associated with a decrease in the protein levels of the mitochondrial Lon protease homolog 1 (LonP1), which is known to target complex IV subunits and PINK1, in addition to other mitochondrial proteins.
30865517	3	87	theme	temporal	603:610	arg1	changes					631:637	temporal and dose-dependent changes	603:637	temporal and dose-dependent changes in O-GlcNAcylation	603:656	This suggests that temporal and dose-dependent changes in O-GlcNAcylation may have different effects on mitochondrial function.
30865517	1	88	theme	cellular	275:282	arg1	compartments					284:295	distinct cellular compartments	266:295	distinct cellular compartments	266:295	The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to the serine and threonine residues of proteins in distinct cellular compartments is increasingly recognized as an important mechanism regulating cellular function.
29530984	4	0	theme	sought-after	935:946	arg1	reaction					948:955	this long sought-after reaction	925:955	this long sought-after reaction	925:955	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	10	1	theme	lipids	1863:1868	arg1	production					1814:1823	the production	1810:1823	the production of previously unanticipated signaling lipids by cytochrome c	1810:1884	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	2	theme	cytochrome	1873:1882	arg1	c					1884:1884	cytochrome c	1873:1884	cytochrome c	1873:1884	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	1	3	theme	critical	181:188	arg1	phospholipids					167:179	phospholipids	167:179	phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position	167:346	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	3	theme	critical	181:188	arg1	Plasmalogens					150:161	Plasmalogens	150:161	Plasmalogens	150:161	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	3	4	from	c	500:500	arg1	presence					510:517	the presence	506:517	the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2	506:580	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	1	5	theme	sn-1	264:267	arg1	position					269:276	the sn-1 position	260:276	the sn-1 position	260:276	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	4	6	theme	high-mass-accuracy	857:874	arg1	MS					876:877	high-mass-accuracy MS	857:877	high-mass-accuracy MS	857:877	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	1	7	theme	sn-2	334:337	arg1	position					339:346	the sn-2 position	330:346	the sn-2 position	330:346	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	10	8	from	plasmenylcholine	1628:1643	arg1	bilayers					1657:1664	membrane bilayers	1648:1664	membrane bilayers	1648:1664	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	8	9	theme	2-AA-lysolipids	1369:1383	arg1	labeling					1357:1364	no significant labeling	1342:1364	no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2	1342:1411	Importantly, no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2 was present.
29530984	10	10	from	perspectives	1903:1914	arg1	signaling					1928:1936	cellular signaling	1919:1936	cellular signaling during oxidative stress	1919:1960	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	3	11	theme	aldehydes	761:769	arg1	cleavage					672:679	hydrolytic cleavage	661:679	hydrolytic cleavage	661:679	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	3	11	theme	aldehydes	761:769	arg1	production					695:704	resultant production	685:704	resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	685:769	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	10	12	theme	unanticipated	1839:1851	arg1	lipids					1863:1868	previously unanticipated signaling lipids	1828:1868	previously unanticipated signaling lipids	1828:1868	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	1	13	from	acid	317:320	arg1	enriched					293:300	enriched	293:300	enriched	293:300	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	5	14	with	reactions	1095:1103	arg1	H218O					1124:1128	H218O	1124:1128	H218O	1124:1128	Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue.
29530984	5	14	with	reactions	1095:1103	arg1	18O2					1115:1118	18O2	1115:1118	18O2	1115:1118	Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue.
29530984	10	15	theme	specific	1695:1702	arg1	mAb					1704:1706	a specific mAb	1693:1706	a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress	1693:1960	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	3	16	theme	reactive	736:743	arg1	aldehydes					761:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	3	17	theme	ether	632:636	arg1	linkage					638:644	the plasmalogen vinyl ether linkage	610:644	the plasmalogen vinyl ether linkage	610:644	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	6	18	theme	18O	1195:1197	arg1	incorporation					1178:1190	incorporation	1178:1190	incorporation of 18O from 18O2	1178:1207	Furthermore, incorporation of 18O from 18O2 was predominantly located at the α-carbon.
29530984	10	19	from	plasmalogenase	1776:1789	arg1	biology					1794:1800	biology	1794:1800	biology	1794:1800	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	3	20	theme	α-hydroxy	745:753	arg1	aldehydes					761:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	0	21	theme	vinyl	129:133	arg1	linkage					141:147	the sn-1 vinyl ether linkage	120:147	the sn-1 vinyl ether linkage	120:147	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	3	22	theme	linkage	638:644	arg1	oxidation					597:605	the oxidation	593:605	the oxidation of the plasmalogen vinyl ether linkage	593:644	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	5	23	theme	M	1145:1145	arg1	isotopologue					1151:1162	the M + 4 isotopologue	1141:1162	isotopologue	1151:1162	Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue.
29530984	3	24	theme	cytochrome	489:498	arg1	c					500:500	cytochrome c	489:500	cytochrome c	489:500	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	1	25	theme	cell	194:197	arg1	function					199:206	cell function	194:206	cell function	194:206	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	0	26	theme	sn-1	124:127	arg1	linkage					141:147	the sn-1 vinyl ether linkage	120:147	the sn-1 vinyl ether linkage	120:147	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	3	27	theme	plasmalogen	614:624	arg1	linkage					638:644	the plasmalogen vinyl ether linkage	610:644	the plasmalogen vinyl ether linkage	610:644	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	3	28	theme	fatty	755:759	arg1	aldehydes					761:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	10	29	theme	signaling	1853:1861	arg1	lipids					1863:1868	previously unanticipated signaling lipids	1828:1868	previously unanticipated signaling lipids	1828:1868	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	0	30	theme	Cytochrome	0:9	arg1	plasmalogenase					46:59	an oxidative stress-activated plasmalogenase	16:59	an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage	16:147	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	0	30	theme	Cytochrome	0:9	arg1	c					11:11	Cytochrome c	0:11	Cytochrome c	0:11	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	5	31	with	labeling	972:979	arg1	H218O2					1021:1026	H218O2	1021:1026	H218O2	1021:1026	Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue.
29530984	5	31	with	labeling	972:979	arg1	18O2					993:996	18O2	993:996	18O2	993:996	Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue.
29530984	2	32	theme	ether	414:418	arg1	linkage					420:426	the vinyl ether linkage	404:426	the vinyl ether linkage	404:426	However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive.
29530984	3	33	theme	vinyl	626:630	arg1	linkage					638:644	the plasmalogen vinyl ether linkage	610:644	the plasmalogen vinyl ether linkage	610:644	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	4	34	theme	isotope	785:791	arg1	labeling					793:800	stable isotope labeling	778:800	stable isotope labeling	778:800	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	10	35	dep	c	1727:1727	arg1	present					1891:1897	present	1891:1897	present new perspectives on cellular signaling during oxidative stress	1891:1960	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	35	dep	c	1727:1727	arg1	reveal					1803:1808	reveal	1803:1808	reveal the production of previously unanticipated signaling lipids by cytochrome c	1803:1884	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	35	dep	c	1727:1727	arg1	identify					1757:1764	identify	1757:1764	identify the first plasmalogenase in biology	1757:1800	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	36	theme	myocardial	1566:1575	arg1	mitochondria					1577:1588	myocardial mitochondria	1566:1588	myocardial mitochondria subjected to oxidative stress	1566:1618	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	2	37	theme	vinyl	408:412	arg1	linkage					420:426	the vinyl ether linkage	404:426	the vinyl ether linkage	404:426	However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive.
29530984	1	38	from	enriched	293:300	arg1	AA					323:324	AA	323:324	AA	323:324	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	38	from	enriched	293:300	arg1	acid					317:320	arachidonic acid	305:320	arachidonic acid (AA) at the sn-2 position	305:346	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	10	39	theme	cytochrome	1716:1725	arg1	c					1727:1727	cytochrome c	1716:1727	cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress	1716:1960	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	2	40	theme	enzyme	362:367	arg1	s					369:369	the enzyme(s)	358:370	the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens	358:442	However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive.
29530984	3	41	theme	hydrolytic	661:670	arg1	cleavage					672:679	hydrolytic cleavage	661:679	hydrolytic cleavage	661:679	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	10	42	theme	new	1899:1901	arg1	perspectives					1903:1914	new perspectives	1899:1914	new perspectives on cellular signaling during oxidative stress	1899:1960	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	0	43	theme	ether	135:139	arg1	linkage					141:147	the sn-1 vinyl ether linkage	120:147	the sn-1 vinyl ether linkage	120:147	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	3	44	theme	oxidized	563:570	arg1	CL					572:573	CL	572:573	CL	572:573	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	7	45	theme	aldehyde	1312:1319	arg1	carbon					1321:1326	the aldehyde carbon	1308:1326	the aldehyde carbon	1308:1326	In contrast, reactions with H218O yielded 18O linked to the aldehyde carbon.
29530984	9	46	theme	phosphatidylinositol	1440:1459	arg1	PIP2					1473:1476	PIP2	1473:1476	PIP2	1473:1476	Intriguingly, phosphatidylinositol phosphates (PIP2 and PIP3) effectively substituted for cardiolipin.
29530984	9	46	theme	phosphatidylinositol	1440:1459	arg1	phosphates					1461:1470	phosphatidylinositol phosphates	1440:1470	phosphatidylinositol phosphates (PIP2 and PIP3)	1440:1486	Intriguingly, phosphatidylinositol phosphates (PIP2 and PIP3) effectively substituted for cardiolipin.
29530984	9	46	theme	phosphatidylinositol	1440:1459	arg1	PIP3					1482:1485	PIP3	1482:1485	PIP3	1482:1485	Intriguingly, phosphatidylinositol phosphates (PIP2 and PIP3) effectively substituted for cardiolipin.
29530984	0	47	theme	stress-activated	29:44	arg1	plasmalogenase					46:59	an oxidative stress-activated plasmalogenase	16:59	an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage	16:147	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	0	47	theme	stress-activated	29:44	arg1	c					11:11	Cytochrome c	0:11	Cytochrome c	0:11	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	1	48	theme	arachidonic	305:315	arg1	AA					323:324	AA	323:324	AA	323:324	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	48	theme	arachidonic	305:315	arg1	acid					317:320	arachidonic acid	305:320	arachidonic acid (AA) at the sn-2 position	305:346	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	3	49	theme	CL	572:573	arg1	presence					510:517	the presence	506:517	the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2	506:580	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	10	50	theme	oxidative	1945:1953	arg1	stress					1955:1960	oxidative stress	1945:1960	oxidative stress	1945:1960	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	0	51	theme	oxidative	19:27	arg1	plasmalogenase					46:59	an oxidative stress-activated plasmalogenase	16:59	an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage	16:147	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	0	51	theme	oxidative	19:27	arg1	c					11:11	Cytochrome c	0:11	Cytochrome c	0:11	Cytochrome c is an oxidative stress-activated plasmalogenase that cleaves plasmenylcholine and plasmenylethanolamine at the sn-1 vinyl ether linkage.
29530984	3	52	theme	resultant	685:693	arg1	production					695:704	resultant production	685:704	resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	685:769	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	1	53	from	position	339:346	arg1	AA					323:324	AA	323:324	AA	323:324	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	53	from	position	339:346	arg1	acid					317:320	arachidonic acid	305:320	arachidonic acid (AA) at the sn-2 position	305:346	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	9	54	dep	phosphates	1461:1470	arg1	PIP2					1473:1476	PIP2	1473:1476	PIP2	1473:1476	Intriguingly, phosphatidylinositol phosphates (PIP2 and PIP3) effectively substituted for cardiolipin.
29530984	9	54	dep	phosphates	1461:1470	arg1	phosphates					1461:1470	phosphatidylinositol phosphates	1440:1470	phosphatidylinositol phosphates (PIP2 and PIP3)	1440:1486	Intriguingly, phosphatidylinositol phosphates (PIP2 and PIP3) effectively substituted for cardiolipin.
29530984	9	54	dep	phosphates	1461:1470	arg1	PIP3					1482:1485	PIP3	1482:1485	PIP3	1482:1485	Intriguingly, phosphatidylinositol phosphates (PIP2 and PIP3) effectively substituted for cardiolipin.
29530984	1	55	theme	vinyl	237:241	arg1	linkage					249:255	a vinyl ether linkage	235:255	a vinyl ether linkage	235:255	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	10	56	theme	cytochrome	1539:1548	arg1	c					1550:1550	cytochrome c	1539:1550	cytochrome c released from myocardial mitochondria subjected to oxidative stress	1539:1618	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	5	57	theme	α-hydroxyaldehyde	1068:1084	arg1	M					1041:1041	M	1041:1041	M	1041:1041	Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue.
29530984	4	58	theme	chemical	828:835	arg1	derivatizations					837:851	strategic chemical derivatizations	818:851	strategic chemical derivatizations	818:851	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	6	59	from	α-carbon	1242:1249	arg1	located					1227:1233	located	1227:1233	located	1227:1233	Furthermore, incorporation of 18O from 18O2 was predominantly located at the α-carbon.
29530984	3	60	theme	cardiolipin	529:539	arg1	presence					510:517	the presence	506:517	the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2	506:580	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29530984	4	61	theme	stable	778:783	arg1	labeling					793:800	stable isotope labeling	778:800	stable isotope labeling	778:800	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	2	62	theme	linkage	420:426	arg1	cleavage					392:399	the cleavage	388:399	the cleavage of the vinyl ether linkage in plasmalogens	388:442	However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive.
29530984	4	63	theme	strategic	818:826	arg1	derivatizations					837:851	strategic chemical derivatizations	818:851	strategic chemical derivatizations	818:851	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	10	64	theme	oxidative	1603:1611	arg1	stress					1613:1618	oxidative stress	1603:1618	oxidative stress	1603:1618	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	65	theme	membrane	1648:1655	arg1	bilayers					1657:1664	membrane bilayers	1648:1664	membrane bilayers	1648:1664	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	66	theme	cellular	1919:1926	arg1	signaling					1928:1936	cellular signaling	1919:1936	cellular signaling during oxidative stress	1919:1960	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	67	attach	released	1552:1559	arg1	mitochondria					1577:1588	myocardial mitochondria	1566:1588	myocardial mitochondria subjected to oxidative stress	1566:1618	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	10	67	attach	released	1552:1559	arg2	c					1550:1550	cytochrome c	1539:1550	cytochrome c released from myocardial mitochondria subjected to oxidative stress	1539:1618	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	7	68	attach	linked	1298:1303	arg1	carbon					1321:1326	the aldehyde carbon	1308:1326	the aldehyde carbon	1308:1326	In contrast, reactions with H218O yielded 18O linked to the aldehyde carbon.
29530984	7	68	attach	linked	1298:1303	arg2	18O					1294:1296	18O	1294:1296	18O linked to the aldehyde carbon	1294:1326	In contrast, reactions with H218O yielded 18O linked to the aldehyde carbon.
29530984	4	69	with	synergy	805:811	arg1	derivatizations					837:851	strategic chemical derivatizations	818:851	strategic chemical derivatizations	818:851	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	4	69	with	synergy	805:811	arg1	MS					876:877	high-mass-accuracy MS	857:877	high-mass-accuracy MS	857:877	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	1	70	theme	ether	243:247	arg1	linkage					249:255	a vinyl ether linkage	235:255	a vinyl ether linkage	235:255	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	71	contain	contain	227:233	arg1	phospholipids					167:179	phospholipids	167:179	phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position	167:346	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	71	contain	contain	227:233	arg2	Plasmalogens					150:161	Plasmalogens	150:161	Plasmalogens	150:161	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	71	contain	contain	227:233	arg2	phospholipids					167:179	phospholipids	167:179	phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position	167:346	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	71	contain	contain	227:233	arg2	linkage					249:255	a vinyl ether linkage	235:255	a vinyl ether linkage	235:255	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	71	contain	contain	227:233	arg1	position					269:276	the sn-1 position	260:276	the sn-1 position	260:276	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	1	71	contain	contain	227:233	arg1	Plasmalogens					150:161	Plasmalogens	150:161	Plasmalogens	150:161	Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl ether linkage at the sn-1 position and are highly enriched in arachidonic acid (AA) at the sn-2 position.
29530984	10	72	theme	first	1770:1774	arg1	plasmalogenase					1776:1789	the first plasmalogenase	1766:1789	the first plasmalogenase in biology	1766:1800	Moreover, cytochrome c released from myocardial mitochondria subjected to oxidative stress cleaved plasmenylcholine in membrane bilayers, and this was blocked with a specific mAb against cytochrome c Collectively, these results identify the first plasmalogenase in biology, reveal the production of previously unanticipated signaling lipids by cytochrome c, and present new perspectives on cellular signaling during oxidative stress.
29530984	8	73	with	labeling	1357:1364	arg1	H218O					1396:1400	H218O	1396:1400	H218O	1396:1400	Importantly, no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2 was present.
29530984	8	73	with	labeling	1357:1364	arg1	H218O2					1406:1411	H218O2	1406:1411	H218O2	1406:1411	Importantly, no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2 was present.
29530984	8	73	with	labeling	1357:1364	arg1	18O2					1390:1393	18O2	1390:1393	18O2	1390:1393	Importantly, no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2 was present.
29530984	4	74	theme	long	930:933	arg1	reaction					948:955	this long sought-after reaction	925:955	this long sought-after reaction	925:955	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	5	75	theme	4	1149:1149	arg1	isotopologue					1151:1162	the M + 4 isotopologue	1141:1162	isotopologue	1151:1162	Specifically, labeling with either 18O2 or H218O, but not with H218O2, resulted in M + 2 isotopologues of the α-hydroxyaldehyde, whereas reactions with both 18O2 and H218O identified the M + 4 isotopologue.
29530984	2	76	theme	responsible	372:382	arg1	s					369:369	the enzyme(s)	358:370	the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens	358:442	However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive.
29530984	8	77	theme	significant	1345:1355	arg1	labeling					1357:1364	no significant labeling	1342:1364	no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2	1342:1411	Importantly, no significant labeling of 2-AA-lysolipids with 18O2, H218O, or H218O2 was present.
29530984	6	78	located	located	1227:1233	arg1	α-carbon					1242:1249	the α-carbon	1238:1249	the α-carbon	1238:1249	Furthermore, incorporation of 18O from 18O2 was predominantly located at the α-carbon.
29530984	6	78	located	located	1227:1233	arg2	incorporation					1178:1190	incorporation	1178:1190	incorporation of 18O from 18O2	1178:1207	Furthermore, incorporation of 18O from 18O2 was predominantly located at the α-carbon.
29530984	7	79	with	reactions	1265:1273	arg1	H218O					1280:1284	H218O	1280:1284	H218O	1280:1284	In contrast, reactions with H218O yielded 18O linked to the aldehyde carbon.
29530984	6	80	from	18O2	1204:1207	arg1	incorporation					1178:1190	incorporation	1178:1190	incorporation of 18O from 18O2	1178:1207	Furthermore, incorporation of 18O from 18O2 was predominantly located at the α-carbon.
29530984	2	81	from	cleavage	392:399	arg1	plasmalogens					431:442	plasmalogens	431:442	plasmalogens	431:442	However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive.
29530984	4	82	theme	chemical	895:902	arg1	mechanism					904:912	the chemical mechanism	891:912	the chemical mechanism underlying this long sought-after reaction	891:955	Using stable isotope labeling in synergy with strategic chemical derivatizations and high-mass-accuracy MS, we deduced the chemical mechanism underlying this long sought-after reaction.
29530984	3	83	theme	2-AA-lysolipids	709:723	arg1	aldehydes					761:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes	709:769	Herein, we report that cytochrome c, in the presence of either cardiolipin (CL), O2 and H2O2, or oxidized CL and O2, catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes.
29402915	0	0	theme	renal	86:90	arg1	cells					107:111	renal and intestinal cells	86:111	renal and intestinal cells	86:111	Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
29402915	3	1	theme	IGS	711:713	arg1	patients					715:722	IGS patients	711:722	IGS patients	711:722	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	0	2	from	targeting	62:70	arg1	cells					107:111	renal and intestinal cells	86:111	renal and intestinal cells	86:111	Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
29402915	8	3	theme	cubilin	1513:1519	arg1	trafficking					1498:1508	membrane trafficking	1489:1508	membrane trafficking of cubilin	1489:1519	These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
29402915	7	4	theme	surface	1417:1423	arg1	targeting					1425:1433	its surface targeting	1413:1433	its surface targeting	1413:1433	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	1	5	theme	low-molecular	328:340	arg1	proteinuria					349:359	low-molecular weight proteinuria	328:359	low-molecular weight proteinuria	328:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	8	6	theme	renal	1524:1528	arg1	cells					1545:1549	renal and intestinal cells	1524:1549	renal and intestinal cells	1524:1549	These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
29402915	1	7	theme	hereditary	218:227	arg1	disease					229:235	a hereditary disease	216:235	a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria	216:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	1	7	theme	hereditary	218:227	arg1	syndrome					200:207	Imerslund-Gräsbeck syndrome	181:207	Imerslund-Gräsbeck syndrome (IGS)	181:213	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	0	8	theme	intestinal	96:105	arg1	cells					107:111	renal and intestinal cells	86:111	renal and intestinal cells	86:111	Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
29402915	1	9	theme	weight	342:347	arg1	proteinuria					349:359	low-molecular weight proteinuria	328:359	low-molecular weight proteinuria	328:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	5	10	theme	renal	1045:1049	arg1	cells					1068:1072	renal proximal tubular cells	1045:1072	renal proximal tubular cells of a patient with IGS	1045:1094	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	8	11	theme	membrane	1489:1496	arg1	trafficking					1498:1508	membrane trafficking	1489:1508	membrane trafficking of cubilin	1489:1519	These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
29402915	4	12	theme	reported	767:774	arg1	mutations					790:798	several previously reported CUBN missense mutations	748:798	several previously reported CUBN missense mutations	748:798	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	4	13	theme	cubilin	976:982	arg1	expression					962:971	amnionless-dependent plasma membrane expression	925:971	amnionless-dependent plasma membrane expression of cubilin	925:982	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	1	14	theme	proteinuria	349:359	arg1	malabsorption					297:309	selective intestinal malabsorption	276:309	selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria	276:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	6	15	theme	cubilin	1214:1220	arg1	glycosylation					1197:1209	amnionless-mediated glycosylation	1177:1209	amnionless-mediated glycosylation of cubilin	1177:1220	Notably, the interaction between cubilin and amnionless was not sufficient, but amnionless-mediated glycosylation of cubilin was necessary for their surface expression.
29402915	5	16	with	patient	1079:1085	arg1	IGS					1092:1094	IGS	1092:1094	IGS	1092:1094	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	3	17	located	found	702:706	arg2	mutations					692:700	mutations	692:700	mutations found in IGS patients	692:722	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	3	17	located	found	702:706	arg1	patients					715:722	IGS patients	711:722	IGS patients	711:722	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	8	18	from	mechanisms	1475:1484	arg1	cells					1545:1549	renal and intestinal cells	1524:1549	renal and intestinal cells	1524:1549	These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
29402915	4	19	theme	missense	781:788	arg1	mutations					790:798	several previously reported CUBN missense mutations	748:798	several previously reported CUBN missense mutations	748:798	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	1	20	theme	amnionless	152:161	arg1	genes					169:173	amnionless (AMN) genes	152:173	amnionless (AMN) genes	152:173	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	0	21	theme	surface	54:60	arg1	targeting					62:70	cell surface targeting	49:70	cell surface targeting of cubilin in renal and intestinal cells	49:111	Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
29402915	4	22	theme	CUBN	776:779	arg1	mutations					790:798	several previously reported CUBN missense mutations	748:798	several previously reported CUBN missense mutations	748:798	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	8	23	theme	intestinal	1534:1543	arg1	cells					1545:1549	renal and intestinal cells	1524:1549	renal and intestinal cells	1524:1549	These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
29402915	5	24	theme	proximal	1051:1058	arg1	cells					1068:1072	renal proximal tubular cells	1045:1072	renal proximal tubular cells of a patient with IGS	1045:1094	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	6	25	theme	amnionless-mediated	1177:1195	arg1	glycosylation					1197:1209	amnionless-mediated glycosylation	1177:1209	amnionless-mediated glycosylation of cubilin	1177:1220	Notably, the interaction between cubilin and amnionless was not sufficient, but amnionless-mediated glycosylation of cubilin was necessary for their surface expression.
29402915	4	26	theme	reticulum	875:883	arg1	retention					890:898	endoplasmic reticulum (ER) retention	863:898	endoplasmic reticulum (ER) retention	863:898	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	7	27	theme	Quantitative	1266:1277	arg1	spectrometry					1284:1295	Quantitative mass spectrometry	1266:1295	Quantitative mass spectrometry	1266:1295	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	3	28	theme	membrane	569:576	arg1	targeting					578:586	membrane targeting	569:586	membrane targeting of the protein complex in cultured renal and intestinal cells	569:648	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	7	29	link	N-linked	1331:1338	arg1	glycosylation					1340:1352	N-linked glycosylation	1331:1352	N-linked glycosylation of at least 4 residues of cubilin protein	1331:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	1	30	theme	AMN	164:166	arg1	genes					169:173	amnionless (AMN) genes	152:173	amnionless (AMN) genes	152:173	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	0	31	theme	Amnionless-mediated	0:18	arg1	glycosylation					20:32	Amnionless-mediated glycosylation	0:32	Amnionless-mediated glycosylation	0:32	Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
29402915	4	32	theme	endoplasmic	863:873	arg1	ER					886:887	ER	886:887	ER	886:887	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	4	32	theme	endoplasmic	863:873	arg1	reticulum					875:883	endoplasmic reticulum	863:883	endoplasmic reticulum (ER) retention	863:898	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	1	33	from	Mutations	114:122	arg1	CUBN					143:146	CUBN	143:146	CUBN	143:146	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	1	33	from	Mutations	114:122	arg1	cubilin					134:140	cubilin	134:140	cubilin (CUBN)	134:147	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	1	33	from	Mutations	114:122	arg1	genes					169:173	amnionless (AMN) genes	152:173	amnionless (AMN) genes	152:173	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	4	34	theme	CUBN	733:736	arg1	mutation					738:745	A novel CUBN mutation	725:745	A novel CUBN mutation	725:745	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	7	35	theme	mass	1279:1282	arg1	spectrometry					1284:1295	Quantitative mass spectrometry	1266:1295	Quantitative mass spectrometry	1266:1295	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	7	36	theme	cubilin	1380:1386	arg1	protein					1388:1394	cubilin protein	1380:1394	cubilin protein	1380:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	4	37	theme	membrane	953:960	arg1	expression					962:971	amnionless-dependent plasma membrane expression	925:971	amnionless-dependent plasma membrane expression of cubilin	925:982	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	8	38	theme	molecular	1465:1473	arg1	mechanisms					1475:1484	the molecular mechanisms	1461:1484	the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells	1461:1549	These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
29402915	4	39	theme	several	748:754	arg1	mutations					790:798	several previously reported CUBN missense mutations	748:798	several previously reported CUBN missense mutations	748:798	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	4	40	theme	AMN	828:830	arg1	mutations					841:849	all previously reported AMN missense mutations	804:849	all previously reported AMN missense mutations	804:849	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	4	41	theme	plasma	946:951	arg1	expression					962:971	amnionless-dependent plasma membrane expression	925:971	amnionless-dependent plasma membrane expression of cubilin	925:982	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	5	42	theme	ER	989:990	arg1	retention					992:1000	The ER retention	985:1000	The ER retention of cubilin and amnionless	985:1026	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	7	43	theme	residues	1368:1375	arg1	glycosylation					1340:1352	N-linked glycosylation	1331:1352	N-linked glycosylation of at least 4 residues of cubilin protein	1331:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	0	44	theme	cell	49:52	arg1	targeting					62:70	cell surface targeting	49:70	cell surface targeting of cubilin in renal and intestinal cells	49:111	Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
29402915	2	45	theme	transmembrane	403:415	arg1	segment					417:423	a transmembrane segment	401:423	a transmembrane segment	401:423	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	3	46	theme	protein	595:601	arg1	complex					603:609	the protein complex	591:609	the protein complex	591:609	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	1	47	theme	Imerslund-Gräsbeck	181:198	arg1	disease					229:235	a hereditary disease	216:235	a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria	216:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	1	47	theme	Imerslund-Gräsbeck	181:198	arg1	IGS					210:212	IGS	210:212	IGS	210:212	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	1	47	theme	Imerslund-Gräsbeck	181:198	arg1	syndrome					200:207	Imerslund-Gräsbeck syndrome	181:207	Imerslund-Gräsbeck syndrome (IGS)	181:213	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	7	48	theme	protein	1388:1394	arg1	residues					1368:1375	at least 4 residues	1357:1375	at least 4 residues of cubilin protein	1357:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	7	48	theme	protein	1388:1394	arg1	protein					1388:1394	cubilin protein	1380:1394	cubilin protein	1380:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	1	49	theme	selective	276:284	arg1	malabsorption					297:309	selective intestinal malabsorption	276:309	selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria	276:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	3	50	theme	intestinal	633:642	arg1	cells					644:648	cultured renal and intestinal cells	614:648	cultured renal and intestinal cells	614:648	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	3	51	theme	complex	603:609	arg1	targeting					578:586	membrane targeting	569:586	membrane targeting of the protein complex in cultured renal and intestinal cells	569:648	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	6	52	gly	glycosylation	1197:1209	arg1	cubilin					1214:1220	cubilin	1214:1220	cubilin	1214:1220	Notably, the interaction between cubilin and amnionless was not sufficient, but amnionless-mediated glycosylation of cubilin was necessary for their surface expression.
29402915	1	53	theme	intestinal	286:295	arg1	malabsorption					297:309	selective intestinal malabsorption	276:309	selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria	276:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	2	54	contain	have	396:399	arg1	protein					379:385	cubilin protein	371:385	cubilin protein	371:385	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	2	54	contain	have	396:399	arg2	segment					417:423	a transmembrane segment	401:423	a transmembrane segment	401:423	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	5	55	theme	tubular	1060:1066	arg1	cells					1068:1072	renal proximal tubular cells	1045:1072	renal proximal tubular cells of a patient with IGS	1045:1094	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	4	56	theme	amnionless-dependent	925:944	arg1	expression					962:971	amnionless-dependent plasma membrane expression	925:971	amnionless-dependent plasma membrane expression of cubilin	925:982	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	2	57	theme	multi-ligand	444:455	arg1	receptor					457:464	a multi-ligand receptor	442:464	a multi-ligand receptor	442:464	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	2	57	theme	multi-ligand	444:455	arg1	it					426:427	it	426:427	it	426:427	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	7	58	gly	glycosylation	1340:1352	arg1	residues					1368:1375	at least 4 residues	1357:1375	at least 4 residues of cubilin protein	1357:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	7	58	gly	glycosylation	1340:1352	arg1	surface					1417:1423	its surface targeting	1413:1433	its surface targeting	1413:1433	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	7	58	gly	glycosylation	1340:1352	arg1	protein					1388:1394	cubilin protein	1380:1394	cubilin protein	1380:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	4	59	theme	missense	832:839	arg1	mutations					841:849	all previously reported AMN missense mutations	804:849	all previously reported AMN missense mutations	804:849	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	8	60	theme	trafficking	1498:1508	arg1	mechanisms					1475:1484	the molecular mechanisms	1461:1484	the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells	1461:1549	These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
29402915	3	61	theme	mutations	692:700	arg1	mechanisms					678:687	the pathogenic mechanisms	663:687	the pathogenic mechanisms of mutations found in IGS patients	663:722	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	5	62	theme	amnionless	1017:1026	arg1	retention					992:1000	The ER retention	985:1000	The ER retention of cubilin and amnionless	985:1026	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	3	63	theme	renal	623:627	arg1	cells					644:648	cultured renal and intestinal cells	614:648	cultured renal and intestinal cells	614:648	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	4	64	theme	reported	819:826	arg1	mutations					841:849	all previously reported AMN missense mutations	804:849	all previously reported AMN missense mutations	804:849	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	4	65	theme	novel	727:731	arg1	mutation					738:745	A novel CUBN mutation	725:745	A novel CUBN mutation	725:745	A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin.
29402915	5	66	theme	patient	1079:1085	arg1	cells					1068:1072	renal proximal tubular cells	1045:1072	renal proximal tubular cells of a patient with IGS	1045:1094	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	5	67	theme	cubilin	1005:1011	arg1	retention					992:1000	The ER retention	985:1000	The ER retention of cubilin and amnionless	985:1026	The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS.
29402915	7	68	theme	N-linked	1331:1338	arg1	glycosylation					1340:1352	N-linked glycosylation	1331:1352	N-linked glycosylation of at least 4 residues of cubilin protein	1331:1394	Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting.
29402915	0	69	theme	cubilin	75:81	arg1	targeting					62:70	cell surface targeting	49:70	cell surface targeting of cubilin in renal and intestinal cells	49:111	Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
29402915	3	70	theme	pathogenic	667:676	arg1	mechanisms					678:687	the pathogenic mechanisms	663:687	the pathogenic mechanisms of mutations found in IGS patients	663:722	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	2	71	theme	cubilin	371:377	arg1	protein					379:385	cubilin protein	371:385	cubilin protein	371:385	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	3	72	from	targeting	578:586	arg1	cells					644:648	cultured renal and intestinal cells	614:648	cultured renal and intestinal cells	614:648	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	2	73	theme	transmembrane	484:496	arg1	amnionless					507:516	amnionless	507:516	amnionless	507:516	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	2	73	theme	transmembrane	484:496	arg1	protein					498:504	the transmembrane protein	480:504	the transmembrane protein	480:504	Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless.
29402915	1	74	theme	cobalamin	314:322	arg1	malabsorption					297:309	selective intestinal malabsorption	276:309	selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria	276:359	Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund-Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria.
29402915	3	75	theme	cultured	614:621	arg1	cells					644:648	cultured renal and intestinal cells	614:648	cultured renal and intestinal cells	614:648	We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients.
29402915	6	76	theme	surface	1246:1252	arg1	expression					1254:1263	their surface expression	1240:1263	their surface expression	1240:1263	Notably, the interaction between cubilin and amnionless was not sufficient, but amnionless-mediated glycosylation of cubilin was necessary for their surface expression.
31371405	4	0	theme	residue	936:942	arg1	mutation					919:926	mutation	919:926	mutation of this residue	919:942	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	1	1	theme	important	160:168	arg1	mechanism					177:185	an important repair mechanism	157:185	an important repair mechanism that is not well understood at present	157:224	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	1	1	theme	important	160:168	arg1	injury					147:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	3	2	theme	glycosylation	785:797	arg1	pathway					799:805	this glycosylation pathway	780:805	this glycosylation pathway	780:805	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	5	3	theme	important	1041:1049	arg1	role					1051:1054	an important role	1038:1054	an important role	1038:1054	These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans.
31371405	1	4	theme	repair	170:175	arg1	mechanism					177:185	an important repair mechanism	157:185	an important repair mechanism that is not well understood at present	157:224	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	1	4	theme	repair	170:175	arg1	injury					147:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	3	5	theme	conserved	514:522	arg1	pathway					538:544	a conserved glycosylation pathway	512:544	a conserved glycosylation pathway	512:544	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	4	6	from	domain	907:912	arg1	located					882:888	located	882:888	located	882:888	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	0	7	theme	Caenorhabditis	86:99	arg1	elegans					101:107	Caenorhabditis elegans	86:107	Caenorhabditis elegans	86:107	N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans.
31371405	2	8	contain	contains	333:340	arg2	domain					354:359	a discoidin domain	342:359	a discoidin domain	342:359	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	8	contain	contains	333:340	arg1	DDR-2					288:292	DDR-2	288:292	DDR-2	288:292	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	8	contain	contains	333:340	arg1	RTK					323:325	RTK	323:325	RTK	323:325	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	8	contain	contains	333:340	arg1	kinase					315:320	a receptor tyrosine kinase	295:320	a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	295:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	3	9	theme	glycosylation	524:536	arg1	pathway					538:544	a conserved glycosylation pathway	512:544	a conserved glycosylation pathway	512:544	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	10	theme	svh-11	471:476	arg1	genes					478:482	the svh-10/sqv-3 and svh-11 genes	450:482	genes	478:482	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	10	theme	svh-11	471:476	arg1	components					498:507	components	498:507	components of a conserved glycosylation pathway	498:544	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	2	11	theme	Met-like	379:386	arg1	pathway					423:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	3	12	theme	axon	667:670	arg1	defect					685:690	the axon regeneration defect	663:690	the axon regeneration defect observed in svh-11 mutants	663:717	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	5	13	from	regeneration	1064:1075	arg1	elegans					1083:1089	C. elegans	1080:1089	C. elegans	1080:1089	These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans.
31371405	3	14	theme	regeneration	672:683	arg1	defect					685:690	the axon regeneration defect	663:690	the axon regeneration defect observed in svh-11 mutants	663:717	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	15	located	observed	692:699	arg1	mutants					711:717	svh-11 mutants	704:717	svh-11 mutants	704:717	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	15	located	observed	692:699	arg2	defect					685:690	the axon regeneration defect	663:690	the axon regeneration defect observed in svh-11 mutants	663:717	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	5	16	theme	axon	1059:1062	arg1	regeneration					1064:1075	axon regeneration	1059:1075	axon regeneration in C. elegans	1059:1089	These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans.
31371405	2	17	theme	tyrosine	306:313	arg1	DDR-2					288:292	DDR-2	288:292	DDR-2	288:292	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	17	theme	tyrosine	306:313	arg1	RTK					323:325	RTK	323:325	RTK	323:325	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	17	theme	tyrosine	306:313	arg1	kinase					315:320	a receptor tyrosine kinase	295:320	a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	295:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	0	18	theme	Discoidin	23:31	arg1	Receptor					40:47	the Discoidin Domain Receptor	19:47	the Discoidin Domain Receptor	19:47	N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans.
31371405	4	19	theme	located	882:888	arg1	residue					874:880	the Asn-141 residue	862:880	the Asn-141 residue located in its discoidin domain	862:912	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	2	20	theme	receptor	297:304	arg1	DDR-2					288:292	DDR-2	288:292	DDR-2	288:292	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	20	theme	receptor	297:304	arg1	RTK					323:325	RTK	323:325	RTK	323:325	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	20	theme	receptor	297:304	arg1	kinase					315:320	a receptor tyrosine kinase	295:320	a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	295:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	21	theme	kinase	406:411	arg1	pathway					423:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	22	theme	signaling	413:421	arg1	pathway					423:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	3	23	theme	svh-2	625:629	arg1	Overexpression					607:620	C. elegans Overexpression	596:620	C. elegans Overexpression of svh-2, but not of ddr-2,	596:648	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	1	24	theme	Axon	110:113	arg1	mechanism					177:185	an important repair mechanism	157:185	an important repair mechanism that is not well understood at present	157:224	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	1	24	theme	Axon	110:113	arg1	injury					147:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	2	25	theme	MAP	402:404	arg1	pathway					423:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	0	26	theme	Receptor	40:47	arg1	N-Glycosylation					0:14	N-Glycosylation	0:14	N-Glycosylation of the Discoidin Domain Receptor	0:47	N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans.
31371405	3	27	theme	svh-11	704:709	arg1	mutants					711:717	svh-11 mutants	704:717	svh-11 mutants	704:717	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	0	28	from	Regeneration	70:81	arg1	elegans					101:107	Caenorhabditis elegans	86:107	Caenorhabditis elegans	86:107	N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans.
31371405	0	29	gly	N-Glycosylation	0:14	arg1	Receptor					40:47	the Discoidin Domain Receptor	19:47	the Discoidin Domain Receptor	19:47	N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans.
31371405	2	30	theme	RTK-JNK	394:400	arg1	pathway					423:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	0	31	theme	Domain	33:38	arg1	Receptor					40:47	the Discoidin Domain Receptor	19:47	the Discoidin Domain Receptor	19:47	N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans.
31371405	4	32	from	located	882:888	arg1	domain					907:912	its discoidin domain	893:912	its discoidin domain	893:912	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	2	33	theme	Caenorhabditis	230:243	arg1	elegans					245:251	Caenorhabditis elegans	230:251	Caenorhabditis elegans	230:251	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	2	34	theme	SVH-2	388:392	arg1	pathway					423:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway	375:429	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	4	35	theme	regeneration	959:970	arg1	defect					972:977	an axon regeneration defect	951:977	an axon regeneration defect	951:977	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	4	36	from	residue	874:880	arg1	N-glycosylated					844:857	N-glycosylated	844:857	N-glycosylated	844:857	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	3	37	dep	C.	596:597	arg1	elegans					599:605	elegans	599:605	elegans	599:605	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	1	38	theme	regeneration	115:126	arg1	mechanism					177:185	an important repair mechanism	157:185	an important repair mechanism that is not well understood at present	157:224	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	1	38	theme	regeneration	115:126	arg1	injury					147:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	4	39	theme	axon	954:957	arg1	defect					972:977	an axon regeneration defect	951:977	an axon regeneration defect	951:977	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	1	40	theme	following	128:136	arg1	mechanism					177:185	an important repair mechanism	157:185	an important repair mechanism that is not well understood at present	157:224	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	1	40	theme	following	128:136	arg1	injury					147:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	5	41	link	N-linked	1009:1016	arg1	glycosylation					1018:1030	N-linked glycosylation	1009:1030	N-linked glycosylation	1009:1030	These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans.
31371405	4	42	theme	Asn-141	866:872	arg1	residue					874:880	the Asn-141 residue	862:880	the Asn-141 residue located in its discoidin domain	862:912	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	3	43	theme	ddr-2	643:647	arg1	Overexpression					607:620	C. elegans Overexpression	596:620	C. elegans Overexpression of svh-2, but not of ddr-2,	596:648	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	44	theme	C.	596:597	arg1	Overexpression					607:620	C. elegans Overexpression	596:620	C. elegans Overexpression of svh-2, but not of ddr-2,	596:648	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	45	theme	axon	575:578	arg1	regeneration					580:591	axon regeneration	575:591	axon regeneration	575:591	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	1	46	theme	neuronal	138:145	arg1	mechanism					177:185	an important repair mechanism	157:185	an important repair mechanism that is not well understood at present	157:224	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	1	46	theme	neuronal	138:145	arg1	injury					147:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury	110:152	Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present.
31371405	3	47	theme	pathway	538:544	arg1	genes					478:482	the svh-10/sqv-3 and svh-11 genes	450:482	genes	478:482	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	47	theme	pathway	538:544	arg1	components					498:507	components	498:507	components of a conserved glycosylation pathway	498:544	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	5	48	theme	N-linked	1009:1016	arg1	glycosylation					1018:1030	N-linked glycosylation	1009:1030	N-linked glycosylation	1009:1030	These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans.
31371405	3	49	theme	svh-10/sqv-3	454:465	arg1	genes					478:482	the svh-10/sqv-3 and svh-11 genes	450:482	genes	478:482	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	3	49	theme	svh-10/sqv-3	454:465	arg1	components					498:507	components	498:507	components of a conserved glycosylation pathway	498:544	Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway.
31371405	0	50	theme	Axon	65:68	arg1	Regeneration					70:81	Axon Regeneration	65:81	Axon Regeneration in Caenorhabditis elegans	65:107	N-Glycosylation of the Discoidin Domain Receptor Is Required for Axon Regeneration in Caenorhabditis elegans.
31371405	2	51	theme	axon	254:257	arg1	regeneration					259:270	axon regeneration	254:270	axon regeneration	254:270	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	4	52	gly	N-glycosylated	844:857	arg1	DDR-2					835:839	DDR-2	835:839	DDR-2	835:839	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	4	52	gly	N-glycosylated	844:857	arg2	residue					874:880	the Asn-141 residue	862:880	the Asn-141 residue located in its discoidin domain	862:912	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31371405	5	53	theme	C.	1080:1081	arg1	elegans					1083:1089	C. elegans	1080:1089	C. elegans	1080:1089	These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans.
31371405	2	54	theme	discoidin	344:352	arg1	domain					354:359	a discoidin domain	342:359	a discoidin domain	342:359	In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK-JNK MAP kinase signaling pathway.
31371405	4	55	theme	discoidin	897:905	arg1	domain					907:912	its discoidin domain	893:912	its discoidin domain	893:912	Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect.
31133022	2	0	theme	LIP	567:569	arg1	action					557:562	action	557:562	action	557:562	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	8	1	theme	sialyl	1598:1603	arg1	structures					1631:1640	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	structures	1631:1640	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	4	2	theme	C-terminal	852:861	arg1	module					873:878	a C-terminal aerolysin module	850:878	a C-terminal aerolysin module	850:878	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	2	3	theme	action	557:562	arg1	mode					549:552	the mode	545:552	the mode of action of LIP, which involves dual selective recognition and efficient binding	545:634	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	7	4	theme	N-linked	1399:1406	arg1	glycans					1408:1414	both N-linked glycans	1394:1414	both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts	1394:1487	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	8	5	theme	X-containing	1611:1622	arg1	structures					1631:1640	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	structures	1631:1640	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	3	6	theme	LIP	701:703	arg1	structure					688:696	the overall crystallographic structure	659:696	the overall crystallographic structure of LIP	659:703	RESULTS We determined the overall crystallographic structure of LIP at a resolution of 2.25 Å.
31133022	1	7	theme	tumor	237:241	arg1	cells					243:247	tumor cells	237:247	tumor cells	237:247	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	2	8	theme	dual	587:590	arg1	recognition					602:612	dual selective recognition	587:612	dual selective recognition	587:612	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	9	9	theme	marine	1893:1898	arg1	protein					1900:1906	a marine protein	1891:1906	a marine protein	1891:1906	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	6	10	theme	normal	1208:1213	arg1	cells					1215:1219	normal cells	1208:1219	normal cells	1208:1219	We found that LIP is able to kill various human cancer cells with minimal effects on normal cells.
31133022	7	11	theme	GPI-anchored	1419:1430	arg1	proteins					1432:1439	GPI-anchored proteins	1419:1439	GPI-anchored proteins (GPI-APs)	1419:1449	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	7	11	theme	GPI-anchored	1419:1430	arg1	GPI-APs					1442:1448	GPI-APs	1442:1448	GPI-APs	1442:1448	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	7	12	from	proteins	1432:1439	arg1	rafts					1483:1487	lipid rafts	1477:1487	lipid rafts	1477:1487	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	6	13	theme	cancer	1171:1176	arg1	cells					1178:1182	various human cancer cells	1157:1182	various human cancer cells	1157:1182	We found that LIP is able to kill various human cancer cells with minimal effects on normal cells.
31133022	9	14	theme	cancer	1925:1930	arg1	therapy					1932:1938	targeted cancer therapy	1916:1938	targeted cancer therapy	1916:1938	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	1	15	theme	lamprey	171:177	arg1	LIP					195:197	LIP	195:197	LIP	195:197	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	1	15	theme	lamprey	171:177	arg1	protein					186:192	lamprey immune protein	171:192	lamprey immune protein (LIP)	171:198	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	2	16	theme	mass	500:503	arg1	analysis					519:526	mass spectrometric analysis	500:526	mass spectrometric analysis	500:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	16	theme	mass	500:503	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	0	17	from	mechanism	62:70	arg1	killing					99:105	the selective killing	85:105	the selective killing of cancer cells	85:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	17	from	mechanism	62:70	arg1	lamprey					46:52	lamprey	46:52	lamprey	46:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	6	18	theme	minimal	1189:1195	arg1	effects					1197:1203	minimal effects	1189:1203	minimal effects on normal cells	1189:1219	We found that LIP is able to kill various human cancer cells with minimal effects on normal cells.
31133022	6	19	from	effects	1197:1203	arg1	cells					1215:1219	normal cells	1208:1219	normal cells	1208:1219	We found that LIP is able to kill various human cancer cells with minimal effects on normal cells.
31133022	8	20	with	binding	1512:1518	arg1	N-glycan					1586:1593	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	N-glycan	1586:1593	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	8	20	with	binding	1512:1518	arg1	structures					1631:1640	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	structures	1631:1640	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	6	21	theme	human	1165:1169	arg1	cells					1178:1182	various human cancer cells	1157:1182	various human cancer cells	1157:1182	We found that LIP is able to kill various human cancer cells with minimal effects on normal cells.
31133022	2	22	theme	FACS	461:464	arg1	assays					466:471	FACS assays	461:471	FACS assays	461:471	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	0	23	from	action	75:80	arg1	killing					99:105	the selective killing	85:105	the selective killing of cancer cells	85:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	5	24	theme	hydrophilic	1092:1102	arg1	lumen					1104:1108	the hydrophilic lumen	1088:1108	the hydrophilic lumen of the pore	1088:1120	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	8	25	from	rafts	1823:1827	arg1	formation					1775:1783	the formation	1771:1783	the formation of a membrane-bound oligomer in lipid rafts	1771:1827	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	4	26	contain	containing	807:816	arg2	module					873:878	a C-terminal aerolysin module	850:878	a C-terminal aerolysin module	850:878	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	4	26	contain	containing	807:816	arg1	105 Å × 30 Å × 30 Å					787:805	105 Å × 30 Å × 30 Å	787:805	105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module	787:878	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	4	26	contain	containing	807:816	arg2	module					839:844	an N-terminal lectin module	818:844	an N-terminal lectin module	818:844	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	5	27	from	face	1030:1033	arg1	β-barrel					986:993	a transmembrane β-barrel	970:993	a transmembrane β-barrel	970:993	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	1	28	theme	killing	301:307	arg1	mechanism					258:266	the mechanism	254:266	the mechanism of the selective recognition and killing of tumor cells by LIP	254:329	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	8	29	theme	membrane-bound	1790:1803	arg1	oligomer					1805:1812	a membrane-bound oligomer	1788:1812	a membrane-bound oligomer in lipid rafts	1788:1827	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	1	30	theme	previous	138:145	arg1	research					147:154	previous research	138:154	previous research	138:154	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	4	31	with	structure	758:766	arg1	dimensions					773:782	dimensions	773:782	dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module	773:878	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	0	32	theme	action	75:80	arg1	mechanism					62:70	its mechanism	58:70	its mechanism of action in the selective killing of cancer cells	58:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	32	theme	action	75:80	arg1	structure					8:16	Crystal structure	0:16	Crystal structure of a cytocidal protein from lamprey	0:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	5	33	theme	polar	1062:1066	arg1	residues					1068:1075	the polar residues	1058:1075	the polar residues	1058:1075	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	7	34	link	N-linked	1399:1406	arg1	glycans					1408:1414	both N-linked glycans	1394:1414	both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts	1394:1487	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	2	35	theme	selective	592:600	arg1	recognition					602:612	dual selective recognition	587:612	dual selective recognition	587:612	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	8	36	from	structures	1631:1640	arg1	GPI-APs					1645:1651	GPI-APs	1645:1651	GPI-APs	1645:1651	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	8	37	from	changes	1689:1695	arg1	module					1714:1719	the aerolysin module	1700:1719	the aerolysin module	1700:1719	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	0	38	theme	Crystal	0:6	arg1	structure					8:16	Crystal structure	0:16	Crystal structure of a cytocidal protein from lamprey	0:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	4	39	theme	lectin	832:837	arg1	module					839:844	an N-terminal lectin module	818:844	an N-terminal lectin module	818:844	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	2	40	theme	structural	404:413	arg1	analysis					415:422	crystallographic structural analysis	387:422	crystallographic structural analysis	387:422	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	40	theme	structural	404:413	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	7	41	theme	computational	1259:1271	arg1	studies					1273:1279	coupling biochemical and computational studies	1234:1279	coupling biochemical and computational studies	1234:1279	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	4	42	theme	105 Å × 30 Å × 30 Å	787:805	arg1	dimensions					773:782	dimensions	773:782	dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module	773:878	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	2	43	theme	Superresolution	359:373	arg1	microscopy					375:384	Superresolution microscopy	359:384	Superresolution microscopy	359:384	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	43	theme	Superresolution	359:373	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	0	44	theme	cytocidal	23:31	arg1	protein					33:39	a cytocidal protein	21:39	a cytocidal protein from lamprey	21:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	5	45	theme	pore	1117:1120	arg1	lumen					1104:1108	the hydrophilic lumen	1088:1108	the hydrophilic lumen of the pore	1088:1120	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	7	46	theme	lipid	1477:1481	arg1	rafts					1483:1487	lipid rafts	1477:1487	lipid rafts	1477:1487	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	8	47	gly	bisialylated	1558:1569	arg1	N-glycan					1586:1593	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	N-glycan	1586:1593	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	7	48	theme	biochemical	1243:1253	arg1	studies					1273:1279	coupling biochemical and computational studies	1234:1279	coupling biochemical and computational studies	1234:1279	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	2	49	theme	chip	432:435	arg1	assay					437:441	glycan chip assay	425:441	glycan chip assay	425:441	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	49	theme	chip	432:435	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	1	50	theme	recognition	285:295	arg1	mechanism					258:266	the mechanism	254:266	the mechanism of the selective recognition and killing of tumor cells by LIP	254:329	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	5	51	theme	hydrophobic	1009:1019	arg1	residues					1021:1028	the hydrophobic residues	1005:1028	the hydrophobic residues	1005:1028	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	8	52	theme	module	1534:1539	arg1	binding					1512:1518	specific binding	1503:1518	specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs	1503:1651	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	8	53	theme	glycan	1624:1629	arg1	structures					1631:1640	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	structures	1631:1640	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	5	54	theme	transmembrane	972:984	arg1	β-barrel					986:993	a transmembrane β-barrel	970:993	a transmembrane β-barrel	970:993	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	9	55	theme	great	1852:1856	arg1	potential					1858:1866	great potential	1852:1866	great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans	1852:1968	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	8	56	theme	biantennary	1546:1556	arg1	N-glycan					1586:1593	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	N-glycan	1586:1593	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	9	57	from	diagnosis	1950:1958	arg1	humans					1963:1968	humans	1963:1968	humans	1963:1968	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	0	58	from	killing	99:105	arg1	mechanism					62:70	its mechanism	58:70	its mechanism of action in the selective killing of cancer cells	58:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	58	from	killing	99:105	arg1	structure					8:16	Crystal structure	0:16	Crystal structure of a cytocidal protein from lamprey	0:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	3	59	theme	crystallographic	671:686	arg1	structure					688:696	the overall crystallographic structure	659:696	the overall crystallographic structure of LIP	659:703	RESULTS We determined the overall crystallographic structure of LIP at a resolution of 2.25 Å.
31133022	1	60	theme	cytocidal	210:218	arg1	activity					220:227	cytocidal activity	210:227	cytocidal activity against tumor cells	210:247	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	8	61	theme	conformational	1674:1687	arg1	changes					1689:1695	substantial conformational changes	1662:1695	substantial conformational changes in the aerolysin module, which interacts with SM	1662:1744	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	3	62	dep	RESULTS	637:643	arg1	determined					648:657	determined	648:657	determined the overall crystallographic structure of LIP at a resolution of 2.25 Å	648:729	RESULTS We determined the overall crystallographic structure of LIP at a resolution of 2.25 Å.
31133022	4	63	theme	aerolysin	863:871	arg1	module					873:878	a C-terminal aerolysin module	850:878	a C-terminal aerolysin module	850:878	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	8	64	theme	Lewis	1605:1609	arg1	structures					1631:1640	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	structures	1631:1640	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	2	65	theme	glycan	425:430	arg1	assay					437:441	glycan chip assay	425:441	glycan chip assay	425:441	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	65	theme	glycan	425:430	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	4	66	theme	N-terminal	821:830	arg1	module					839:844	an N-terminal lectin module	818:844	an N-terminal lectin module	818:844	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	9	67	theme	protein	1900:1906	arg1	application					1876:1886	the application	1872:1886	the application of a marine protein	1872:1906	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	8	68	theme	aerolysin	1704:1712	arg1	module					1714:1719	the aerolysin module	1700:1719	the aerolysin module	1700:1719	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	7	69	theme	dependent	1381:1389	arg1	recognition					1347:1357	dual selective recognition	1332:1357	dual selective recognition	1332:1357	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	9	70	theme	targeted	1916:1923	arg1	therapy					1932:1938	targeted cancer therapy	1916:1938	targeted cancer therapy	1916:1938	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	3	71	theme	2.25 Å	724:729	arg1	resolution					710:719	a resolution	708:719	a resolution of 2.25 Å	708:729	RESULTS We determined the overall crystallographic structure of LIP at a resolution of 2.25 Å.
31133022	8	72	from	N-glycan	1586:1593	arg1	GPI-APs					1645:1651	GPI-APs	1645:1651	GPI-APs	1645:1651	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	2	73	theme	spectrometric	505:517	arg1	analysis					519:526	mass spectrometric analysis	500:526	mass spectrometric analysis	500:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	73	theme	spectrometric	505:517	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	7	74	theme	efficient	1363:1371	arg1	binding					1373:1379	efficient binding	1363:1379	efficient binding	1363:1379	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	8	75	from	formation	1775:1783	arg1	rafts					1823:1827	lipid rafts	1817:1827	lipid rafts	1817:1827	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	0	76	theme	cells	117:121	arg1	killing					99:105	the selective killing	85:105	the selective killing of cancer cells	85:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	1	77	contain	possessed	200:208	arg2	activity					220:227	cytocidal activity	210:227	cytocidal activity against tumor cells	210:247	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	1	77	contain	possessed	200:208	arg1	LIP					195:197	LIP	195:197	LIP	195:197	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	1	77	contain	possessed	200:208	arg1	protein					186:192	lamprey immune protein	171:192	lamprey immune protein (LIP)	171:198	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	1	78	theme	immune	179:184	arg1	LIP					195:197	LIP	195:197	LIP	195:197	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	1	78	theme	immune	179:184	arg1	protein					186:192	lamprey immune protein	171:192	lamprey immune protein (LIP)	171:198	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	9	79	theme	early	1944:1948	arg1	diagnosis					1950:1958	early diagnosis	1944:1958	early diagnosis	1944:1958	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	5	80	theme	Phe209-Gly232	895:907	arg1	region					909:914	the Phe209-Gly232 region	891:914	the Phe209-Gly232 region	891:914	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	7	81	from	sphingomyelin	1455:1467	arg1	rafts					1483:1487	lipid rafts	1477:1487	lipid rafts	1477:1487	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	7	82	theme	dual	1332:1335	arg1	recognition					1347:1357	dual selective recognition	1332:1357	dual selective recognition	1332:1357	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	8	83	from	oligomer	1805:1812	arg1	rafts					1823:1827	lipid rafts	1817:1827	lipid rafts	1817:1827	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	6	84	theme	various	1157:1163	arg1	cells					1178:1182	various human cancer cells	1157:1182	various human cancer cells	1157:1182	We found that LIP is able to kill various human cancer cells with minimal effects on normal cells.
31133022	5	85	theme	lipid	1039:1043	arg1	bilayer					1045:1051	the lipid bilayer	1035:1051	the lipid bilayer	1035:1051	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	7	86	theme	hypothetical	1295:1306	arg1	mechanism					1308:1316	a hypothetical mechanism	1293:1316	a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts	1293:1487	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	1	87	theme	tumor	312:316	arg1	cells					318:322	tumor cells	312:322	tumor cells	312:322	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	2	88	theme	SPR	444:446	arg1	experiments					448:458	SPR experiments	444:458	SPR experiments	444:458	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	0	89	from	structure	8:16	arg1	killing					99:105	the selective killing	85:105	the selective killing of cancer cells	85:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	89	from	structure	8:16	arg1	lamprey					46:52	lamprey	46:52	lamprey	46:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	2	90	theme	efficient	618:626	arg1	binding					628:634	efficient binding	618:634	efficient binding	618:634	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	5	91	theme	lipid	948:952	arg1	bilayer					954:960	the lipid bilayer	944:960	the lipid bilayer	944:960	Moreover, the Phe209-Gly232 region is predicted to insert into the lipid bilayer to form a transmembrane β-barrel, in which the hydrophobic residues face the lipid bilayer, and the polar residues constitute the hydrophilic lumen of the pore.
31133022	7	92	from	glycans	1408:1414	arg1	proteins					1432:1439	GPI-anchored proteins	1419:1439	GPI-anchored proteins (GPI-APs)	1419:1449	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	7	92	from	glycans	1408:1414	arg1	SM					1470:1471	SM	1470:1471	SM	1470:1471	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	7	92	from	glycans	1408:1414	arg1	GPI-APs					1442:1448	GPI-APs	1442:1448	GPI-APs	1442:1448	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	7	92	from	glycans	1408:1414	arg1	sphingomyelin					1455:1467	sphingomyelin	1455:1467	sphingomyelin (SM)	1455:1472	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	2	93	theme	computational	474:486	arg1	studies					488:494	computational studies	474:494	computational studies	474:494	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	0	94	from	lamprey	46:52	arg1	mechanism					62:70	its mechanism	58:70	its mechanism of action in the selective killing of cancer cells	58:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	94	from	lamprey	46:52	arg1	protein					33:39	a cytocidal protein	21:39	a cytocidal protein from lamprey	21:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	94	from	lamprey	46:52	arg1	structure					8:16	Crystal structure	0:16	Crystal structure of a cytocidal protein from lamprey	0:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	95	theme	selective	89:97	arg1	killing					99:105	the selective killing	85:105	the selective killing of cancer cells	85:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	1	96	theme	cells	318:322	arg1	killing					301:307	killing	301:307	killing of tumor cells by LIP	301:329	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	1	96	theme	cells	318:322	arg1	recognition					285:295	the selective recognition	271:295	the selective recognition	271:295	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	8	97	theme	oligomer	1805:1812	arg1	formation					1775:1783	the formation	1771:1783	the formation of a membrane-bound oligomer in lipid rafts	1771:1827	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	9	98	from	therapy	1932:1938	arg1	humans					1963:1968	humans	1963:1968	humans	1963:1968	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	8	99	theme	lipid	1817:1821	arg1	rafts					1823:1827	lipid rafts	1817:1827	lipid rafts	1817:1827	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	8	100	theme	specific	1503:1510	arg1	binding					1512:1518	specific binding	1503:1518	specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs	1503:1651	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	7	101	theme	selective	1337:1345	arg1	recognition					1347:1357	dual selective recognition	1332:1357	dual selective recognition	1332:1357	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	9	102	theme	CONCLUSIONS	1830:1840	arg1	LIP					1842:1844	CONCLUSIONS LIP	1830:1844	CONCLUSIONS LIP	1830:1844	CONCLUSIONS LIP holds great potential for the application of a marine protein towards targeted cancer therapy and early diagnosis in humans.
31133022	2	103	theme	crystallographic	387:402	arg1	analysis					415:422	crystallographic structural analysis	387:422	crystallographic structural analysis	387:422	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	103	theme	crystallographic	387:402	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	1	104	dep	BACKGROUND	124:133	arg1	research					147:154	previous research	138:154	previous research	138:154	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	0	105	theme	protein	33:39	arg1	mechanism					62:70	its mechanism	58:70	its mechanism of action in the selective killing of cancer cells	58:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	0	105	theme	protein	33:39	arg1	structure					8:16	Crystal structure	0:16	Crystal structure of a cytocidal protein from lamprey	0:52	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	7	106	theme	coupling	1234:1241	arg1	studies					1273:1279	coupling biochemical and computational studies	1234:1279	coupling biochemical and computational studies	1234:1279	Notably, by coupling biochemical and computational studies, we propose a hypothetical mechanism that involves dual selective recognition and efficient binding dependent on both N-linked glycans on GPI-anchored proteins (GPI-APs) and sphingomyelin (SM) in lipid rafts.
31133022	8	107	theme	lectin	1527:1532	arg1	module					1534:1539	the lectin module	1523:1539	the lectin module	1523:1539	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	2	108	dep	METHODS	351:357	arg1	studies					488:494	computational studies	474:494	computational studies	474:494	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	108	dep	METHODS	351:357	arg1	analysis					415:422	crystallographic structural analysis	387:422	crystallographic structural analysis	387:422	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	108	dep	METHODS	351:357	arg1	experiments					448:458	SPR experiments	444:458	SPR experiments	444:458	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	108	dep	METHODS	351:357	arg1	METHODS					351:357	METHODS	351:357	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis	351:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	108	dep	METHODS	351:357	arg1	microscopy					375:384	Superresolution microscopy	359:384	Superresolution microscopy	359:384	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	108	dep	METHODS	351:357	arg1	analysis					519:526	mass spectrometric analysis	500:526	mass spectrometric analysis	500:526	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	108	dep	METHODS	351:357	arg1	assay					437:441	glycan chip assay	425:441	glycan chip assay	425:441	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	2	108	dep	METHODS	351:357	arg1	assays					466:471	FACS assays	461:471	FACS assays	461:471	METHODS Superresolution microscopy, crystallographic structural analysis, glycan chip assay, SPR experiments, FACS assays, computational studies and mass spectrometric analysis firmly establish the mode of action of LIP, which involves dual selective recognition and efficient binding.
31133022	8	109	gly	nonfucosylated	1571:1584	arg1	N-glycan					1586:1593	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	N-glycan	1586:1593	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	0	110	theme	cancer	110:115	arg1	cells					117:121	cancer cells	110:121	cancer cells	110:121	Crystal structure of a cytocidal protein from lamprey and its mechanism of action in the selective killing of cancer cells.
31133022	1	111	theme	selective	275:283	arg1	recognition					285:295	the selective recognition	271:295	the selective recognition	271:295	BACKGROUND In previous research, we found that lamprey immune protein (LIP) possessed cytocidal activity against tumor cells, but the mechanism of the selective recognition and killing of tumor cells by LIP was not identified.
31133022	8	112	theme	bisialylated	1558:1569	arg1	N-glycan					1586:1593	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	N-glycan	1586:1593	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	4	113	theme	elongated	748:756	arg1	structure					758:766	an elongated structure	745:766	an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module	745:878	LIP exhibits an elongated structure with dimensions of 105 Å × 30 Å × 30 Å containing an N-terminal lectin module and a C-terminal aerolysin module.
31133022	3	114	theme	overall	663:669	arg1	structure					688:696	the overall crystallographic structure	659:696	the overall crystallographic structure of LIP	659:703	RESULTS We determined the overall crystallographic structure of LIP at a resolution of 2.25 Å.
31133022	8	115	theme	nonfucosylated	1571:1584	arg1	N-glycan					1586:1593	biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures	1546:1640	N-glycan	1586:1593	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
31133022	8	116	theme	substantial	1662:1672	arg1	changes					1689:1695	substantial conformational changes	1662:1695	substantial conformational changes in the aerolysin module, which interacts with SM	1662:1744	Furthermore, specific binding of the lectin module with biantennary bisialylated nonfucosylated N-glycan or sialyl Lewis X-containing glycan structures on GPI-APs triggers substantial conformational changes in the aerolysin module, which interacts with SM, ultimately resulting in the formation of a membrane-bound oligomer in lipid rafts.
30541852	4	0	theme	functional	470:479	arg1	provirus					481:488	one fully functional provirus	460:488	one fully functional provirus	460:488	We previously identified one fully functional provirus from the sequenced genome of the C57BL/6 mouse strain.
30541852	9	1	theme	infection	1606:1614	arg1	abilities					1616:1624	full infection abilities	1601:1624	full infection abilities	1601:1624	Most of these elements degenerate over time and become nonfunctional, but the mouse genome still contains several families with full infection abilities.
30541852	7	2	theme	first	1053:1057	arg1	loop					1073:1076	the first extracellular loop	1049:1076	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	8	3	attach	present	1445:1451	arg1	vertebrates					1460:1470	all vertebrates	1456:1470	all vertebrates	1456:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	3	attach	present	1445:1451	arg2	traces					1419:1424	genomic traces	1411:1424	genomic traces of past infections present in all vertebrates	1411:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	3	attach	present	1445:1451	arg2	retroviruses					1394:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	7	4	dep	presence	992:999	arg1	the					988:990	the	988:990	the	988:990	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	5	5	theme	host	620:623	arg1	range					625:629	an ecotropic host range	607:629	an ecotropic host range	607:629	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	6	6	theme	folate	847:852	arg1	carrier					854:860	the reduced folate carrier	835:860	the reduced folate carrier	835:860	In this study, we have identified SLC19A1, the reduced folate carrier, as the cellular protein used as a receptor by the GLN retrovirus.
30541852	6	6	theme	folate	847:852	arg1	SLC19A1					826:832	SLC19A1	826:832	SLC19A1	826:832	In this study, we have identified SLC19A1, the reduced folate carrier, as the cellular protein used as a receptor by the GLN retrovirus.
30541852	0	7	theme	GLN	59:61	arg1	Retrovirus					74:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	Identification of the Receptor Used by the Ecotropic Mouse GLN Endogenous Retrovirus.
30541852	8	8	theme	other	1181:1185	arg1	proteins					1207:1214	all the other retroviral envelope proteins	1173:1214	all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified	1173:1282	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	13	9	from	mutation	1930:1937	arg1	hamster					2061:2067	hamster	2061:2067	hamster	2061:2067	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	13	9	from	mutation	1930:1937	arg1	gene					1952:1955	the mouse gene	1942:1955	the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat	1942:2044	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	7	10	theme	glycosylation	1027:1039	arg1	site					1041:1044	an N-linked glycosylation site	1015:1044	an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1015:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	2	11	theme	recent	286:291	arg1	elements					311:318	recent, still-infectious elements	286:318	recent, still-infectious elements capable of encoding complete viral particles	286:363	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	1	12	theme	different	176:184	arg1	families					186:193	different families	176:193	different families	176:193	Approximately 10% of the mouse genome is composed of endogenous retroviruses belonging to different families.
30541852	8	13	theme	envelope	1198:1205	arg1	proteins					1207:1214	all the other retroviral envelope proteins	1173:1214	all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified	1173:1282	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	13	14	theme	SLC19A1	1989:1995	arg1	residues					2012:2019	SLC19A1 and also other residues	1989:2019	SLC19A1 and also other residues conserved within the rat	1989:2044	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	12	15	theme	reduced	1839:1845	arg1	carrier					1854:1860	the reduced folate carrier	1835:1860	the reduced folate carrier	1835:1860	It is SLC19A1, the reduced folate carrier.
30541852	12	15	theme	reduced	1839:1845	arg1	SLC19A1					1826:1832	SLC19A1	1826:1832	SLC19A1	1826:1832	It is SLC19A1, the reduced folate carrier.
30541852	8	16	theme	Endogenous	1383:1392	arg1	retroviruses					1394:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	16	theme	Endogenous	1383:1392	arg1	traces					1419:1424	genomic traces	1411:1424	genomic traces of past infections present in all vertebrates	1411:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	14	17	from	infection	2283:2291	arg1	mammals					2296:2302	mammals	2296:2302	mammals	2296:2302	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	7	18	theme	specific	1093:1100	arg1	sequence					1113:1120	the specific amino acid sequence	1089:1120	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	13	19	dep	both	1923:1926	arg1	mutation					1930:1937	a mutation	1928:1937	a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster	1928:2067	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	8	20	theme	gammaretrovirus	1225:1239	arg1	genus					1241:1245	the gammaretrovirus genus	1221:1245	the gammaretrovirus genus whose receptors have been identified	1221:1282	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	10	21	theme	mouse	1724:1728	arg1	cells					1730:1734	only mouse cells	1719:1734	only mouse cells	1719:1734	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	14	22	theme	solute	2185:2190	arg1	superfamily					2200:2210	the solute carrier superfamily	2181:2210	the solute carrier superfamily	2181:2210	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	5	23	theme	GLN	549:551	arg1	protein					562:568	The GLN envelope protein	545:568	The GLN envelope protein	545:568	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	1	24	theme	genome	117:122	arg1	genome					117:122	the mouse genome	107:122	the mouse genome	107:122	Approximately 10% of the mouse genome is composed of endogenous retroviruses belonging to different families.
30541852	1	24	theme	genome	117:122	arg1	%					102:102	Approximately 10%	86:102	Approximately 10% of the mouse genome	86:122	Approximately 10% of the mouse genome is composed of endogenous retroviruses belonging to different families.
30541852	8	25	theme	past	1429:1432	arg1	infections					1434:1443	past infections	1429:1443	past infections	1429:1443	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	0	26	theme	Mouse	53:57	arg1	Retrovirus					74:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	Identification of the Receptor Used by the Ecotropic Mouse GLN Endogenous Retrovirus.
30541852	8	27	from	present	1445:1451	arg1	vertebrates					1460:1470	all vertebrates	1456:1470	all vertebrates	1456:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	28	theme	present	1445:1451	arg1	retroviruses					1394:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	28	theme	present	1445:1451	arg1	traces					1419:1424	genomic traces	1411:1424	genomic traces of past infections present in all vertebrates	1411:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	0	29	theme	Endogenous	63:72	arg1	Retrovirus					74:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	Identification of the Receptor Used by the Ecotropic Mouse GLN Endogenous Retrovirus.
30541852	13	30	theme	mouse	1946:1950	arg1	gene					1952:1955	the mouse gene	1942:1955	the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat	1942:2044	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	5	31	theme	infectious	580:589	arg1	particles					597:605	the infectious viral particles	576:605	the infectious viral particles	576:605	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	1	32	theme	endogenous	139:148	arg1	retroviruses					150:161	endogenous retroviruses	139:161	endogenous retroviruses belonging to different families	139:193	Approximately 10% of the mouse genome is composed of endogenous retroviruses belonging to different families.
30541852	4	33	theme	sequenced	499:507	arg1	genome					509:514	the sequenced genome	495:514	the sequenced genome of the C57BL/6 mouse strain	495:542	We previously identified one fully functional provirus from the sequenced genome of the C57BL/6 mouse strain.
30541852	7	34	theme	domains	1143:1149	arg1	sequence					1113:1120	the specific amino acid sequence	1089:1120	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	34	theme	domains	1143:1149	arg1	loop					1073:1076	the first extracellular loop	1049:1076	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	8	35	theme	envelope	1293:1300	arg1	protein					1302:1308	the GLN envelope protein	1285:1308	the GLN envelope protein	1285:1308	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	3	36	theme	active	418:423	arg1	families					425:432	these active families	412:432	these active families	412:432	The mouse GLN endogenous retrovirus is one of these active families.
30541852	5	37	theme	envelope	553:560	arg1	protein					562:568	The GLN envelope protein	545:568	The GLN envelope protein	545:568	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	3	38	theme	mouse	370:374	arg1	retrovirus					391:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	38	theme	mouse	370:374	arg1	families					425:432	these active families	412:432	these active families	412:432	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	38	theme	mouse	370:374	arg1	one					405:407	one	405:407	one	405:407	The mouse GLN endogenous retrovirus is one of these active families.
30541852	7	39	from	sequence	1113:1120	arg1	absence					1004:1010	absence	1004:1010	absence	1004:1010	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	39	from	sequence	1113:1120	arg1	presence					992:999	presence	992:999	presence	992:999	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	40	theme	receptor	1158:1165	arg1	domains					1143:1149	the extracellular domains	1125:1149	the extracellular domains of the receptor	1125:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	40	theme	receptor	1158:1165	arg1	receptor					1158:1165	the receptor	1154:1165	the receptor	1154:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	41	theme	site	1041:1044	arg1	absence					1004:1010	absence	1004:1010	absence	1004:1010	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	41	theme	site	1041:1044	arg1	presence					992:999	presence	992:999	presence	992:999	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	4	42	theme	strain	537:542	arg1	genome					509:514	the sequenced genome	495:514	the sequenced genome of the C57BL/6 mouse strain	495:542	We previously identified one fully functional provirus from the sequenced genome of the C57BL/6 mouse strain.
30541852	7	43	theme	amino	1102:1106	arg1	sequence					1113:1120	the specific amino acid sequence	1089:1120	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	6	44	theme	reduced	839:845	arg1	carrier					854:860	the reduced folate carrier	835:860	the reduced folate carrier	835:860	In this study, we have identified SLC19A1, the reduced folate carrier, as the cellular protein used as a receptor by the GLN retrovirus.
30541852	6	44	theme	reduced	839:845	arg1	SLC19A1					826:832	SLC19A1	826:832	SLC19A1	826:832	In this study, we have identified SLC19A1, the reduced folate carrier, as the cellular protein used as a receptor by the GLN retrovirus.
30541852	14	45	theme	other	2098:2102	arg1	gammaretroviruses					2104:2120	all other gammaretroviruses	2094:2120	all other gammaretroviruses whose receptors have been identified	2094:2157	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	5	46	theme	retroviral	762:771	arg1	proteins					782:789	mouse ecotropic retroviral envelope proteins	746:789	mouse ecotropic retroviral envelope proteins	746:789	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	3	47	theme	endogenous	380:389	arg1	retrovirus					391:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	47	theme	endogenous	380:389	arg1	families					425:432	these active families	412:432	these active families	412:432	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	47	theme	endogenous	380:389	arg1	one					405:407	one	405:407	one	405:407	The mouse GLN endogenous retrovirus is one of these active families.
30541852	8	48	theme	carrier	1338:1344	arg1	superfamily					1346:1356	the solute carrier superfamily	1327:1356	the solute carrier superfamily	1327:1356	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	13	49	theme	mouse	1904:1908	arg1	cells					1910:1914	mouse cells	1904:1914	mouse cells	1904:1914	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	10	50	theme	them	1656:1659	arg1	them					1656:1659	them	1656:1659	them	1656:1659	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	10	50	theme	them	1656:1659	arg1	one					1649:1651	one	1649:1651	one	1649:1651	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	10	50	theme	them	1656:1659	arg1	retrovirus					1635:1644	The GLN retrovirus	1627:1644	The GLN retrovirus	1627:1644	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	7	51	from	loop	1073:1076	arg1	absence					1004:1010	absence	1004:1010	absence	1004:1010	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	51	from	loop	1073:1076	arg1	presence					992:999	presence	992:999	presence	992:999	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	14	52	theme	retroviral	2272:2281	arg1	infection					2283:2291	retroviral infection	2272:2291	retroviral infection in mammals	2272:2302	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	11	53	theme	cellular	1761:1768	arg1	protein					1770:1776	the cellular protein	1757:1776	the cellular protein used as a receptor by GLN for cell entry	1757:1817	Here, we identified the cellular protein used as a receptor by GLN for cell entry.
30541852	8	54	theme	receptor.IMPORTANCE	1363:1381	arg1	retroviruses					1394:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	54	theme	receptor.IMPORTANCE	1363:1381	arg1	traces					1419:1424	genomic traces	1411:1424	genomic traces of past infections present in all vertebrates	1411:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	14	55	theme	proteins	2259:2266	arg1	role					2245:2248	the role	2241:2248	the role of these proteins for retroviral infection in mammals	2241:2302	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	0	56	theme	Ecotropic	43:51	arg1	Retrovirus					74:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	the Ecotropic Mouse GLN Endogenous Retrovirus	39:83	Identification of the Receptor Used by the Ecotropic Mouse GLN Endogenous Retrovirus.
30541852	7	57	from	presence	992:999	arg1	loop					1073:1076	the first extracellular loop	1049:1076	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	57	from	presence	992:999	arg1	sequence					1113:1120	the specific amino acid sequence	1089:1120	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	58	theme	extracellular	1059:1071	arg1	loop					1073:1076	the first extracellular loop	1049:1076	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	2	59	theme	complete	340:347	arg1	particles					355:363	complete viral particles	340:363	complete viral particles	340:363	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	13	60	theme	residues	2012:2019	arg1	glycosylation					1972:1984	the glycosylation	1968:1984	the glycosylation of SLC19A1 and also other residues conserved within the rat	1968:2044	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	6	61	theme	cellular	870:877	arg1	protein					879:885	the cellular protein	866:885	the cellular protein used as a receptor by the GLN retrovirus	866:926	In this study, we have identified SLC19A1, the reduced folate carrier, as the cellular protein used as a receptor by the GLN retrovirus.
30541852	6	61	theme	cellular	870:877	arg1	SLC19A1					826:832	SLC19A1	826:832	SLC19A1	826:832	In this study, we have identified SLC19A1, the reduced folate carrier, as the cellular protein used as a receptor by the GLN retrovirus.
30541852	9	62	theme	full	1601:1604	arg1	abilities					1616:1624	full infection abilities	1601:1624	full infection abilities	1601:1624	Most of these elements degenerate over time and become nonfunctional, but the mouse genome still contains several families with full infection abilities.
30541852	7	63	from	absence	1004:1010	arg1	loop					1073:1076	the first extracellular loop	1049:1076	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	63	from	absence	1004:1010	arg1	sequence					1113:1120	the specific amino acid sequence	1089:1120	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	2	64	theme	families	263:270	arg1	several					246:252	several	246:252	several	246:252	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	5	65	theme	ecotropic	610:618	arg1	range					625:629	an ecotropic host range	607:629	an ecotropic host range	607:629	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	7	66	gly	glycosylation	1027:1039	arg2	site					1041:1044	an N-linked glycosylation site	1015:1044	an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1015:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	4	67	theme	C57BL/6	523:529	arg1	strain					537:542	the C57BL/6 mouse strain	519:542	the C57BL/6 mouse strain	519:542	We previously identified one fully functional provirus from the sequenced genome of the C57BL/6 mouse strain.
30541852	5	68	theme	mouse	746:750	arg1	proteins					782:789	mouse ecotropic retroviral envelope proteins	746:789	mouse ecotropic retroviral envelope proteins	746:789	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	7	69	theme	N-linked	1018:1025	arg1	site					1041:1044	an N-linked glycosylation site	1015:1044	an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1015:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	14	70	theme	cell	2216:2219	arg1	entry					2221:2225	cell entry	2216:2225	cell entry	2216:2225	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	10	71	theme	only	1719:1722	arg1	cells					1730:1734	only mouse cells	1719:1734	only mouse cells	1719:1734	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	14	72	theme	superfamily	2200:2210	arg1	member					2171:2176	a member	2169:2176	a member of the solute carrier superfamily	2169:2210	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	6	73	theme	GLN	913:915	arg1	retrovirus					917:926	the GLN retrovirus	909:926	the GLN retrovirus	909:926	In this study, we have identified SLC19A1, the reduced folate carrier, as the cellular protein used as a receptor by the GLN retrovirus.
30541852	8	74	theme	retroviral	1187:1196	arg1	proteins					1207:1214	all the other retroviral envelope proteins	1173:1214	all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified	1173:1282	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	75	theme	genomic	1411:1417	arg1	retroviruses					1394:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	75	theme	genomic	1411:1417	arg1	traces					1419:1424	genomic traces	1411:1424	genomic traces of past infections present in all vertebrates	1411:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	2	76	dep	situation	215:223	arg1	contrast					199:206	contrast	199:206	contrast	199:206	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	9	77	contain	contains	1570:1577	arg2	families					1587:1594	several families	1579:1594	several families with full infection abilities	1579:1624	Most of these elements degenerate over time and become nonfunctional, but the mouse genome still contains several families with full infection abilities.
30541852	9	77	contain	contains	1570:1577	arg1	genome					1557:1562	the mouse genome	1547:1562	the mouse genome	1547:1562	Most of these elements degenerate over time and become nonfunctional, but the mouse genome still contains several families with full infection abilities.
30541852	13	78	theme	other	2006:2010	arg1	residues					2012:2019	SLC19A1 and also other residues	1989:2019	SLC19A1 and also other residues conserved within the rat	1989:2044	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	12	79	theme	folate	1847:1852	arg1	carrier					1854:1860	the reduced folate carrier	1835:1860	the reduced folate carrier	1835:1860	It is SLC19A1, the reduced folate carrier.
30541852	12	79	theme	folate	1847:1852	arg1	SLC19A1					1826:1832	SLC19A1	1826:1832	SLC19A1	1826:1832	It is SLC19A1, the reduced folate carrier.
30541852	14	80	theme	carrier	2192:2198	arg1	superfamily					2200:2210	the solute carrier superfamily	2181:2210	the solute carrier superfamily	2181:2210	Like all other gammaretroviruses whose receptors have been identified, GLN uses a member of the solute carrier superfamily for cell entry, highlighting the role of these proteins for retroviral infection in mammals.
30541852	5	81	theme	viral	591:595	arg1	particles					597:605	the infectious viral particles	576:605	the infectious viral particles	576:605	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	1	82	theme	mouse	111:115	arg1	genome					117:122	the mouse genome	107:122	the mouse genome	107:122	Approximately 10% of the mouse genome is composed of endogenous retroviruses belonging to different families.
30541852	8	83	theme	infections	1434:1443	arg1	retroviruses					1394:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	a receptor.IMPORTANCE Endogenous retroviruses	1361:1405	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	83	theme	infections	1434:1443	arg1	traces					1419:1424	genomic traces	1411:1424	genomic traces of past infections present in all vertebrates	1411:1470	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	2	84	dep	recent	286:291	arg1	still-infectious					294:309	still-infectious	294:309	still-infectious	294:309	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	5	85	theme	identified	721:730	arg1	receptors					732:740	the two previously identified receptors	702:740	the two previously identified receptors for mouse ecotropic retroviral envelope proteins	702:789	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	5	85	theme	identified	721:730	arg1	CAT1					686:689	CAT1	686:689	CAT1	686:689	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	2	86	theme	human	232:236	arg1	genome					238:243	the human genome	228:243	the human genome	228:243	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	7	87	theme	ecotropic	933:941	arg1	tropism					943:949	The ecotropic tropism	929:949	The ecotropic tropism exhibited by this envelope	929:976	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	87	theme	ecotropic	933:941	arg1	due					981:983	due	981:983	due	981:983	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	13	88	dep	hamster	2061:2067	arg1	the					2057:2059	the	2057:2059	the	2057:2059	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	13	89	dep	proteins	2079:2086	arg1	human					2073:2077	human	2073:2077	human	2073:2077	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	13	89	dep	proteins	2079:2086	arg1	both					1923:1926	both	1923:1926	both	1923:1926	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	7	90	theme	extracellular	1129:1141	arg1	domains					1143:1149	the extracellular domains	1125:1149	the extracellular domains of the receptor	1125:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	90	theme	extracellular	1129:1141	arg1	receptor					1158:1165	the receptor	1154:1165	the receptor	1154:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	8	91	from	genus	1241:1245	arg1	proteins					1207:1214	all the other retroviral envelope proteins	1173:1214	all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified	1173:1282	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	8	92	theme	GLN	1289:1291	arg1	protein					1302:1308	the GLN envelope protein	1285:1308	the GLN envelope protein	1285:1308	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	3	93	theme	families	425:432	arg1	retrovirus					391:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	93	theme	families	425:432	arg1	families					425:432	these active families	412:432	these active families	412:432	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	93	theme	families	425:432	arg1	one					405:407	one	405:407	one	405:407	The mouse GLN endogenous retrovirus is one of these active families.
30541852	8	94	from	vertebrates	1460:1470	arg1	present					1445:1451	present	1445:1451	present	1445:1451	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	2	95	from	situation	215:223	arg1	genome					238:243	the human genome	228:243	the human genome	228:243	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	3	96	theme	GLN	376:378	arg1	retrovirus					391:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus	366:400	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	96	theme	GLN	376:378	arg1	families					425:432	these active families	412:432	these active families	412:432	The mouse GLN endogenous retrovirus is one of these active families.
30541852	3	96	theme	GLN	376:378	arg1	one					405:407	one	405:407	one	405:407	The mouse GLN endogenous retrovirus is one of these active families.
30541852	11	97	theme	cell	1808:1811	arg1	entry					1813:1817	cell entry	1808:1817	cell entry	1808:1817	Here, we identified the cellular protein used as a receptor by GLN for cell entry.
30541852	0	98	theme	Receptor	22:29	arg1	Identification					0:13	Identification	0:13	Identification of the Receptor	0:29	Identification of the Receptor Used by the Ecotropic Mouse GLN Endogenous Retrovirus.
30541852	7	99	from	site	1041:1044	arg1	loop					1073:1076	the first extracellular loop	1049:1076	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	7	99	from	site	1041:1044	arg1	sequence					1113:1120	the specific amino acid sequence	1089:1120	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	10	100	theme	GLN	1631:1633	arg1	them					1656:1659	them	1656:1659	them	1656:1659	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	10	100	theme	GLN	1631:1633	arg1	one					1649:1651	one	1649:1651	one	1649:1651	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	10	100	theme	GLN	1631:1633	arg1	retrovirus					1635:1644	The GLN retrovirus	1627:1644	The GLN retrovirus	1627:1644	The GLN retrovirus is one of them, and its members encode particles that are able to infect only mouse cells.
30541852	5	101	theme	ecotropic	752:760	arg1	proteins					782:789	mouse ecotropic retroviral envelope proteins	746:789	mouse ecotropic retroviral envelope proteins	746:789	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	7	102	link	N-linked	1018:1025	arg1	site					1041:1044	an N-linked glycosylation site	1015:1044	an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1015:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30541852	5	103	theme	envelope	773:780	arg1	proteins					782:789	mouse ecotropic retroviral envelope proteins	746:789	mouse ecotropic retroviral envelope proteins	746:789	The GLN envelope protein gives the infectious viral particles an ecotropic host range, and we had demonstrated that the receptor was neither CAT1 nor SMIT1, the two previously identified receptors for mouse ecotropic retroviral envelope proteins.
30541852	9	104	theme	mouse	1551:1555	arg1	genome					1557:1562	the mouse genome	1547:1562	the mouse genome	1547:1562	Most of these elements degenerate over time and become nonfunctional, but the mouse genome still contains several families with full infection abilities.
30541852	4	105	theme	mouse	531:535	arg1	strain					537:542	the C57BL/6 mouse strain	519:542	the C57BL/6 mouse strain	519:542	We previously identified one fully functional provirus from the sequenced genome of the C57BL/6 mouse strain.
30541852	8	106	theme	solute	1331:1336	arg1	superfamily					1346:1356	the solute carrier superfamily	1327:1356	the solute carrier superfamily	1327:1356	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	2	107	theme	capable	320:326	arg1	elements					311:318	recent, still-infectious elements	286:318	recent, still-infectious elements capable of encoding complete viral particles	286:363	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	8	108	theme	superfamily	1346:1356	arg1	member					1317:1322	a member	1315:1322	a member of the solute carrier superfamily	1315:1356	Like all the other retroviral envelope proteins from the gammaretrovirus genus whose receptors have been identified, the GLN envelope protein uses a member of the solute carrier superfamily as a receptor.IMPORTANCE Endogenous retroviruses are genomic traces of past infections present in all vertebrates.
30541852	13	109	theme	GLN	1876:1878	arg1	infection					1880:1888	GLN infection	1876:1888	GLN infection	1876:1888	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	2	110	theme	viral	349:353	arg1	particles					355:363	complete viral particles	340:363	complete viral particles	340:363	In contrast to the situation in the human genome, several of these families correspond to recent, still-infectious elements capable of encoding complete viral particles.
30541852	13	111	gly	glycosylation	1972:1984	arg1	residues					2012:2019	SLC19A1 and also other residues	1989:2019	SLC19A1 and also other residues conserved within the rat	1989:2044	We show that GLN infection is limited to mouse cells due to both a mutation in the mouse gene preventing the glycosylation of SLC19A1 and also other residues conserved within the rat but not in the hamster and human proteins.
30541852	9	112	theme	several	1579:1585	arg1	families					1587:1594	several families	1579:1594	several families with full infection abilities	1579:1624	Most of these elements degenerate over time and become nonfunctional, but the mouse genome still contains several families with full infection abilities.
30541852	9	113	with	families	1587:1594	arg1	abilities					1616:1624	full infection abilities	1601:1624	full infection abilities	1601:1624	Most of these elements degenerate over time and become nonfunctional, but the mouse genome still contains several families with full infection abilities.
30541852	7	114	theme	acid	1108:1111	arg1	sequence					1113:1120	the specific amino acid sequence	1089:1120	the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor	1049:1165	The ecotropic tropism exhibited by this envelope is due to the presence or absence of an N-linked glycosylation site in the first extracellular loop as well as the specific amino acid sequence of the extracellular domains of the receptor.
30029404	0	0	theme	selective	92:100	arg1	enrichment					102:111	on-column selective enrichment	82:111	on-column selective enrichment of N-linked glycopeptides	82:137	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	6	1	theme	nano-LC-MS/MS	1264:1276	arg1	analysis					1278:1285	nano-LC-MS/MS analysis	1264:1285	nano-LC-MS/MS analysis	1264:1285	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	4	2	theme	hydrophilic	911:921	arg1	HILIC					958:962	HILIC	958:962	HILIC	958:962	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	4	2	theme	hydrophilic	911:921	arg1	chromatography					942:955	hydrophilic interaction liquid chromatography	911:955	hydrophilic interaction liquid chromatography (HILIC)	911:963	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	6	3	from	enrichment	1196:1205	arg1	digests					1229:1235	digests	1229:1235	digests of human serum	1229:1250	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	0	4	theme	on-column	82:90	arg1	enrichment					102:111	on-column selective enrichment	82:111	on-column selective enrichment of N-linked glycopeptides	82:137	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	3	5	theme	trap	699:702	arg1	columns					704:710	the trap columns	695:710	the trap columns	695:710	The preparation procedures of the trap columns are well reproducible.
30029404	2	6	theme	spectrometry	610:621	arg1	time					590:593	matrix-assisted laser desorption/ionization time	546:593	matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	546:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	4	7	theme	interaction	923:933	arg1	HILIC					958:962	HILIC	958:962	HILIC	958:962	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	4	7	theme	interaction	923:933	arg1	chromatography					942:955	hydrophilic interaction liquid chromatography	911:955	hydrophilic interaction liquid chromatography (HILIC)	911:963	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	2	8	theme	pretreatment	519:530	arg1	step					532:535	a sample pretreatment step	510:535	a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	510:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	8	theme	pretreatment	519:530	arg1	method					465:470	a novel on-column enrichment method	436:470	a novel on-column enrichment method toward glycopeptides	436:491	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	3	9	theme	columns	704:710	arg1	procedures					681:690	The preparation procedures	665:690	The preparation procedures of the trap columns	665:710	The preparation procedures of the trap columns are well reproducible.
30029404	3	9	theme	columns	704:710	arg1	reproducible					721:732	reproducible	721:732	reproducible	721:732	The preparation procedures of the trap columns are well reproducible.
30029404	2	10	theme	mass	605:608	arg1	spectrometry					610:621	flight mass spectrometry	598:621	flight mass spectrometry (MALDI-TOF MS)	598:636	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	10	theme	mass	605:608	arg1	MS					634:635	MALDI-TOF MS	624:635	MALDI-TOF MS	624:635	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	5	11	theme	HRP	1074:1076	arg1	limit					1059:1063	a low detection limit	1043:1063	a low detection limit (50 fmol HRP digest)	1043:1084	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	5	11	theme	HRP	1074:1076	arg1	digest					1078:1083	50 fmol HRP digest	1066:1083	50 fmol HRP digest	1066:1083	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	4	12	theme	grafted	787:793	arg1	groups					812:817	the grafted zwitterionic IDA groups	783:817	the grafted zwitterionic IDA groups	783:817	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	2	13	gly	glycopeptides	479:491	arg2	glycopeptides					479:491	glycopeptides	479:491	glycopeptides	479:491	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	1	14	theme	silica	261:266	arg1	microspheres					268:279	silica microspheres	261:279	silica microspheres	261:279	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	2	15	theme	sample	512:517	arg1	step					532:535	a sample pretreatment step	510:535	a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	510:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	15	theme	sample	512:517	arg1	method					465:470	a novel on-column enrichment method	436:470	a novel on-column enrichment method toward glycopeptides	436:491	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	1	16	theme	SiO2-IDA	357:364	arg1	columns					381:387	SiO2-IDA capillary trap columns	357:387	SiO2-IDA capillary trap columns	357:387	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	2	17	theme	flight	598:603	arg1	spectrometry					610:621	flight mass spectrometry	598:621	flight mass spectrometry (MALDI-TOF MS)	598:636	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	17	theme	flight	598:603	arg1	MS					634:635	MALDI-TOF MS	624:635	MALDI-TOF MS	624:635	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	18	theme	analysis	655:662	arg1	time					590:593	matrix-assisted laser desorption/ionization time	546:593	matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	546:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	0	19	theme	glycopeptides	125:137	arg1	enrichment					102:111	on-column selective enrichment	82:111	on-column selective enrichment of N-linked glycopeptides	82:137	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	1	20	theme	capillary	366:374	arg1	columns					381:387	SiO2-IDA capillary trap columns	357:387	SiO2-IDA capillary trap columns	357:387	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	2	21	theme	nano-LC-MS/MS	641:653	arg1	analysis					655:662	nano-LC-MS/MS analysis	641:662	nano-LC-MS/MS analysis	641:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	4	22	theme	IDA	808:810	arg1	groups					812:817	the grafted zwitterionic IDA groups	783:817	the grafted zwitterionic IDA groups	783:817	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	6	23	theme	glycopeptides	1210:1222	arg1	enrichment					1196:1205	on-column enrichment	1186:1205	on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis	1186:1285	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	0	24	theme	N-linked	116:123	arg1	glycopeptides					125:137	N-linked glycopeptides	116:137	N-linked glycopeptides	116:137	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	1	25	theme	trap	376:379	arg1	columns					381:387	SiO2-IDA capillary trap columns	357:387	SiO2-IDA capillary trap columns	357:387	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	4	26	theme	enrichment	864:873	arg1	performance					875:885	excellent on-column enrichment performance	844:885	excellent on-column enrichment performance	844:885	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	4	27	theme	zwitterionic	795:806	arg1	groups					812:817	the grafted zwitterionic IDA groups	783:817	the grafted zwitterionic IDA groups	783:817	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	5	28	theme	molar	1110:1114	arg1	ratio					1116:1120	molar ratio	1110:1120	molar ratio of HRP digest and BSA	1110:1142	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	7	29	gly	glycoproteins	1331:1343	arg1	glycoproteins					1331:1343	78 glycoproteins	1328:1343	78 glycoproteins	1328:1343	In total, 207 glycopeptides assigned to 78 glycoproteins were identified from 2 μL human serum.
30029404	5	30	theme	HRP	1125:1127	arg1	digest					1129:1134	HRP digest	1125:1134	HRP digest	1125:1134	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	7	31	gly	glycopeptides	1302:1314	arg2	glycopeptides					1302:1314	207 glycopeptides	1298:1314	207 glycopeptides assigned to 78 glycoproteins	1298:1343	In total, 207 glycopeptides assigned to 78 glycoproteins were identified from 2 μL human serum.
30029404	2	32	theme	MALDI-TOF	624:632	arg1	spectrometry					610:621	flight mass spectrometry	598:621	flight mass spectrometry (MALDI-TOF MS)	598:636	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	32	theme	MALDI-TOF	624:632	arg1	MS					634:635	MALDI-TOF MS	624:635	MALDI-TOF MS	624:635	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	4	33	theme	outstanding	745:755	arg1	hydrophilicity					757:770	outstanding hydrophilicity	745:770	outstanding hydrophilicity brought by the grafted zwitterionic IDA groups	745:817	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	1	34	theme	previous	196:203	arg1	method					205:210	a previous method	194:210	a previous method	194:210	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	0	35	theme	acid	29:32	arg1	Preparation					0:10	Preparation	0:10	Preparation of iminodiacetic acid	0:32	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	2	36	theme	matrix-assisted	546:560	arg1	desorption/ionization					568:588	matrix-assisted laser desorption/ionization	546:588	matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	546:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	7	37	theme	2 μL	1366:1369	arg1	serum					1377:1381	2 μL human serum	1366:1381	2 μL human serum	1366:1381	In total, 207 glycopeptides assigned to 78 glycoproteins were identified from 2 μL human serum.
30029404	5	38	theme	on-column	1003:1011	arg1	method					1024:1029	the on-column enrichment method	999:1029	the on-column enrichment method	999:1029	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	0	39	theme	iminodiacetic	15:27	arg1	acid					29:32	iminodiacetic acid	15:32	iminodiacetic acid	15:32	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	6	40	theme	on-column	1186:1194	arg1	enrichment					1196:1205	on-column enrichment	1186:1205	on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis	1186:1285	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	0	41	gly	glycopeptides	125:137	arg2	glycopeptides					125:137	N-linked glycopeptides	116:137	N-linked glycopeptides	116:137	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	0	42	theme	silica	49:54	arg1	column					71:76	silica capillary trap column	49:76	silica capillary trap column	49:76	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	1	43	theme	SiO2-IDA	291:298	arg1	microspheres					300:311	the SiO2-IDA microspheres	287:311	the SiO2-IDA microspheres	287:311	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	2	44	theme	prior	537:541	arg1	step					532:535	a sample pretreatment step	510:535	a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	510:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	44	theme	prior	537:541	arg1	method					465:470	a novel on-column enrichment method	436:470	a novel on-column enrichment method toward glycopeptides	436:491	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	6	45	theme	serum	1246:1250	arg1	digests					1229:1235	digests	1229:1235	digests of human serum	1229:1250	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	2	46	theme	enrichment	454:463	arg1	step					532:535	a sample pretreatment step	510:535	a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	510:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	46	theme	enrichment	454:463	arg1	method					465:470	a novel on-column enrichment method	436:470	a novel on-column enrichment method toward glycopeptides	436:491	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	1	47	theme	first	397:401	arg1	time					403:406	the first time	393:406	the first time	393:406	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	5	48	theme	fmol	1069:1072	arg1	limit					1059:1063	a low detection limit	1043:1063	a low detection limit (50 fmol HRP digest)	1043:1084	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	5	48	theme	fmol	1069:1072	arg1	digest					1078:1083	50 fmol HRP digest	1066:1083	50 fmol HRP digest	1066:1083	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	1	49	theme	iminodiacetic	224:236	arg1	IDA					244:246	IDA	244:246	IDA	244:246	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	1	49	theme	iminodiacetic	224:236	arg1	acid					238:241	iminodiacetic acid	224:241	iminodiacetic acid (IDA) groups	224:254	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	0	50	theme	trap	66:69	arg1	column					71:76	silica capillary trap column	49:76	silica capillary trap column	49:76	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	7	51	theme	human	1371:1375	arg1	serum					1377:1381	2 μL human serum	1366:1381	2 μL human serum	1366:1381	In total, 207 glycopeptides assigned to 78 glycoproteins were identified from 2 μL human serum.
30029404	4	52	theme	on-column	854:862	arg1	performance					875:885	excellent on-column enrichment performance	844:885	excellent on-column enrichment performance	844:885	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	5	53	theme	digest	1129:1134	arg1	ratio					1116:1120	molar ratio	1110:1120	molar ratio of HRP digest and BSA	1110:1142	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	0	54	theme	capillary	56:64	arg1	column					71:76	silica capillary trap column	49:76	silica capillary trap column	49:76	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	5	55	theme	BSA	1140:1142	arg1	ratio					1116:1120	molar ratio	1110:1120	molar ratio of HRP digest and BSA	1110:1142	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	2	56	theme	novel	438:442	arg1	step					532:535	a sample pretreatment step	510:535	a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	510:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	56	theme	novel	438:442	arg1	method					465:470	a novel on-column enrichment method	436:470	a novel on-column enrichment method toward glycopeptides	436:491	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	4	57	theme	excellent	844:852	arg1	performance					875:885	excellent on-column enrichment performance	844:885	excellent on-column enrichment performance	844:885	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	4	58	theme	liquid	935:940	arg1	HILIC					958:962	HILIC	958:962	HILIC	958:962	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	4	58	theme	liquid	935:940	arg1	chromatography					942:955	hydrophilic interaction liquid chromatography	911:955	hydrophilic interaction liquid chromatography (HILIC)	911:963	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	5	59	theme	high	1092:1095	arg1	selectivity					1097:1107	a high selectivity	1090:1107	a high selectivity (molar ratio of HRP digest and BSA digest 1:100)	1090:1156	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	2	60	theme	desorption/ionization	568:588	arg1	time					590:593	matrix-assisted laser desorption/ionization time	546:593	matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	546:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	5	61	theme	Experimental	966:977	arg1	results					979:985	Experimental results	966:985	Experimental results	966:985	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	5	62	theme	low	1045:1047	arg1	limit					1059:1063	a low detection limit	1043:1063	a low detection limit (50 fmol HRP digest)	1043:1084	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	5	62	theme	low	1045:1047	arg1	digest					1078:1083	50 fmol HRP digest	1066:1083	50 fmol HRP digest	1066:1083	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	6	63	theme	human	1240:1244	arg1	serum					1246:1250	human serum	1240:1250	human serum	1240:1250	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	6	64	from	digests	1229:1235	arg1	glycopeptides					1210:1222	glycopeptides	1210:1222	glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis	1210:1285	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	6	64	from	digests	1229:1235	arg1	enrichment					1196:1205	on-column enrichment	1186:1205	on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis	1186:1285	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	1	65	theme	acid	238:241	arg1	groups					249:254	iminodiacetic acid (IDA) groups	224:254	iminodiacetic acid (IDA) groups	224:254	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	2	66	theme	laser	562:566	arg1	desorption/ionization					568:588	matrix-assisted laser desorption/ionization	546:588	matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	546:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	3	67	theme	preparation	669:679	arg1	procedures					681:690	The preparation procedures	665:690	The preparation procedures of the trap columns	665:710	The preparation procedures of the trap columns are well reproducible.
30029404	3	67	theme	preparation	669:679	arg1	reproducible					721:732	reproducible	721:732	reproducible	721:732	The preparation procedures of the trap columns are well reproducible.
30029404	5	68	theme	detection	1049:1057	arg1	limit					1059:1063	a low detection limit	1043:1063	a low detection limit (50 fmol HRP digest)	1043:1084	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	5	68	theme	detection	1049:1057	arg1	digest					1078:1083	50 fmol HRP digest	1066:1083	50 fmol HRP digest	1066:1083	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	6	69	gly	glycopeptides	1210:1222	arg1	digests					1229:1235	digests	1229:1235	digests of human serum	1229:1250	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	6	69	gly	glycopeptides	1210:1222	arg2	glycopeptides					1210:1222	glycopeptides	1210:1222	glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis	1210:1285	Finally, it was applied to on-column enrichment of glycopeptides from digests of human serum followed by nano-LC-MS/MS analysis.
30029404	4	70	gly	glycopeptides	894:906	arg2	glycopeptides					894:906	glycopeptides	894:906	glycopeptides	894:906	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	4	71	theme	trap	824:827	arg1	columns					829:835	the trap columns	820:835	the trap columns	820:835	Thanks to outstanding hydrophilicity brought by the grafted zwitterionic IDA groups, the trap columns showed excellent on-column enrichment performance toward glycopeptides by hydrophilic interaction liquid chromatography (HILIC).
30029404	0	72	link	N-linked	116:123	arg1	glycopeptides					125:137	N-linked glycopeptides	116:137	N-linked glycopeptides	116:137	Preparation of iminodiacetic acid functionalized silica capillary trap column for on-column selective enrichment of N-linked glycopeptides.
30029404	5	73	theme	enrichment	1013:1022	arg1	method					1024:1029	the on-column enrichment method	999:1029	the on-column enrichment method	999:1029	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	5	74	dep	selectivity	1097:1107	arg1	digest					1144:1149	digest	1144:1149	digest	1144:1149	Experimental results showed that the on-column enrichment method could reach a low detection limit (50 fmol HRP digest) and a high selectivity (molar ratio of HRP digest and BSA digest 1:100).
30029404	2	75	theme	on-column	444:452	arg1	step					532:535	a sample pretreatment step	510:535	a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis	510:662	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	2	75	theme	on-column	444:452	arg1	method					465:470	a novel on-column enrichment method	436:470	a novel on-column enrichment method toward glycopeptides	436:491	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	1	76	theme	capillary	328:336	arg1	columns					338:344	capillary columns	328:344	capillary columns	328:344	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
30029404	2	77	theme	trap	422:425	arg1	columns					427:433	the trap columns	418:433	the trap columns	418:433	Based on the trap columns, a novel on-column enrichment method toward glycopeptides was developed as a sample pretreatment step prior to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) or nano-LC-MS/MS analysis.
30029404	1	78	theme	SiO2-IDA	154:161	arg1	microspheres					163:174	SiO2-IDA microspheres	154:174	SiO2-IDA microspheres	154:174	In this work, SiO2-IDA microspheres were obtained via a previous method by grafting iminodiacetic acid (IDA) groups onto silica microspheres, then the SiO2-IDA microspheres were packed in capillary columns to prepare SiO2-IDA capillary trap columns for the first time.
31727010	2	0	theme	phosphate	469:477	arg1	conversion					444:453	the conversion	440:453	the conversion of mannose 6- phosphate into mannose 1-phosphate	440:502	The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate.
31727010	1	1	theme	glycolipid	337:346	arg1	glycans					348:354	glycolipid glycans	337:354	glycolipid glycans	337:354	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	5	2	theme	CDG	749:751	arg1	cases					753:757	over 100 new CDG cases	736:757	over 100 new CDG cases	736:757	Now, over 100 new CDG cases have been reported.
31727010	9	3	theme	del	1141:1143	arg1	variant					1145:1151	c.241-242 del variant	1131:1151	c.241-242 del variant	1131:1151	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	9	3	theme	del	1141:1143	arg1	mutation					1121:1128	one novel mutation	1111:1128	one novel mutation (c.241-242 del variant)	1111:1152	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	0	4	theme	ethnic	71:76	arg1	minority					78:85	Hani ethnic minority	66:85	Hani ethnic minority with congenital glycosylation disorders	66:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	1	5	theme	glycans	348:354	arg1	attachment					305:314	attachment	305:314	attachment	305:314	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	5	theme	glycans	348:354	arg1	synthesis					291:299	synthesis	291:299	synthesis	291:299	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	8	6	theme	Hani	961:964	arg1	family					982:987	a Hani ethnic minority family	959:987	a Hani ethnic minority family including two siblings with congenital glycosylation disorders	959:1050	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	0	7	with	minority	78:85	arg1	disorders					117:125	congenital glycosylation disorders	92:125	congenital glycosylation disorders	92:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	1	8	theme	common	161:166	arg1	disorder					191:198	the most common N-linked glycosylation disorder	152:198	the most common N-linked glycosylation disorder	152:198	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	8	theme	common	161:166	arg1	PMM2-CDG					139:146	BACKGROUND PMM2-CDG,	128:147	PMM2-CDG	139:146	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	8	9	theme	ethnic	966:971	arg1	family					982:987	a Hani ethnic minority family	959:987	a Hani ethnic minority family including two siblings with congenital glycosylation disorders	959:1050	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	0	10	theme	congenital	92:101	arg1	disorders					117:125	congenital glycosylation disorders	92:125	congenital glycosylation disorders	92:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	3	11	theme	Most	505:508	arg1	patients					510:517	Most patients	505:517	Most patients with PMM2-CDG	505:531	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	3	12	with	patients	510:517	arg1	PMM2-CDG					524:531	PMM2-CDG	524:531	PMM2-CDG	524:531	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	11	13	theme	normal	1401:1406	arg1	control					1408:1414	the normal control	1397:1414	the normal control	1397:1414	The mutations were identified in this family by Sanger sequencing and no mutations were detected in the normal control.
31727010	1	14	theme	genetic	259:265	arg1	disorders					267:275	genetic disorders	259:275	genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans	259:354	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	4	15	theme	cerebellar	685:694	arg1	ataxia					696:701	cerebellar ataxia	685:701	cerebellar ataxia	685:701	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	8	16	theme	CASE	925:928	arg1	PRESENTATION					930:941	CASE PRESENTATION	925:941	CASE PRESENTATION	925:941	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	8	17	dep	present	951:957	arg1	PRESENTATION					930:941	CASE PRESENTATION	925:941	CASE PRESENTATION	925:941	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	1	18	theme	N-linked	168:175	arg1	disorder					191:198	the most common N-linked glycosylation disorder	152:198	the most common N-linked glycosylation disorder	152:198	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	18	theme	N-linked	168:175	arg1	PMM2-CDG					139:146	BACKGROUND PMM2-CDG,	128:147	PMM2-CDG	139:146	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	0	19	theme	glycosylation	103:115	arg1	disorders					117:125	congenital glycosylation disorders	92:125	congenital glycosylation disorders	92:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	9	20	theme	reported	1169:1176	arg1	mutation					1178:1185	previously reported mutation	1158:1185	previously reported mutation (c.395 T > C) in gene of PMM2	1158:1215	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	9	20	theme	reported	1169:1176	arg1	c.395 T > C					1188:1198	c.395 T > C	1188:1198	c.395 T > C	1188:1198	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	12	21	theme	Hani	1495:1498	arg1	minority					1507:1514	Hani ethnic minority	1495:1514	Hani ethnic minority	1495:1514	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	1	22	dep	synthesis	291:299	arg1	the					287:289	the	287:289	the	287:289	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	23	theme	glycosylation	177:189	arg1	disorder					191:198	the most common N-linked glycosylation disorder	152:198	the most common N-linked glycosylation disorder	152:198	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	23	theme	glycosylation	177:189	arg1	PMM2-CDG					139:146	BACKGROUND PMM2-CDG,	128:147	PMM2-CDG	139:146	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	8	24	theme	minority	973:980	arg1	family					982:987	a Hani ethnic minority family	959:987	a Hani ethnic minority family including two siblings with congenital glycosylation disorders	959:1050	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	0	25	from	findings	36:43	arg1	minority					78:85	Hani ethnic minority	66:85	Hani ethnic minority with congenital glycosylation disorders	66:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	0	25	from	findings	36:43	arg1	siblings					52:59	two siblings	48:59	two siblings from Hani ethnic minority with congenital glycosylation disorders	48:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	1	26	link	N-linked	168:175	arg1	disorder					191:198	the most common N-linked glycosylation disorder	152:198	the most common N-linked glycosylation disorder	152:198	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	26	link	N-linked	168:175	arg1	PMM2-CDG					139:146	BACKGROUND PMM2-CDG,	128:147	PMM2-CDG	139:146	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	2	27	theme	mannose	484:490	arg1	1-phosphate					492:502	mannose 1-phosphate	484:502	mannose 1-phosphate	484:502	The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate.
31727010	9	28	from	mutation	1121:1128	arg1	gene					1204:1207	gene	1204:1207	gene	1204:1207	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	0	29	theme	Clinical	0:7	arg1	findings					36:43	Clinical and whole-exome sequencing findings	0:43	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.	0:126	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	1	30	theme	disorders	267:275	arg1	series					249:254	a series	247:254	a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans	247:354	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	30	theme	disorders	267:275	arg1	syndromes					226:234	all CDG syndromes	218:234	all CDG syndromes	218:234	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	9	31	from	mutation	1178:1185	arg1	gene					1204:1207	gene	1204:1207	gene	1204:1207	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	7	32	theme	few	870:872	arg1	CDGs					874:877	few CDGs	870:877	few CDGs	870:877	In addition, few CDGs have been reported in the Chinese population.
31727010	10	33	located	found	1237:1241	arg2	mutations					1222:1230	Two mutations	1218:1230	Two mutations	1218:1230	Two mutations were found in proband and her sibling by whole-exome sequencing.
31727010	10	33	located	found	1237:1241	arg1	proband					1246:1252	proband	1246:1252	proband	1246:1252	Two mutations were found in proband and her sibling by whole-exome sequencing.
31727010	10	33	located	found	1237:1241	arg1	sibling					1262:1268	her sibling	1258:1268	her sibling by whole-exome sequencing	1258:1294	Two mutations were found in proband and her sibling by whole-exome sequencing.
31727010	9	34	theme	Whole-exome	1053:1063	arg1	sequencing					1065:1074	Whole-exome sequencing	1053:1074	Whole-exome sequencing	1053:1074	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	0	35	theme	sequencing	25:34	arg1	findings					36:43	Clinical and whole-exome sequencing findings	0:43	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.	0:126	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	12	36	theme	ethnic	1537:1542	arg1	groups					1544:1549	five ethnic groups	1532:1549	five ethnic groups found only in Yunnan with a population of more than 1 million	1532:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	8	37	theme	glycosylation	1028:1040	arg1	disorders					1042:1050	congenital glycosylation disorders	1017:1050	congenital glycosylation disorders	1017:1050	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	3	38	theme	nervous	546:552	arg1	involvement					561:571	central nervous system involvement	538:571	central nervous system involvement	538:571	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	8	39	with	siblings	1003:1010	arg1	disorders					1042:1050	congenital glycosylation disorders	1017:1050	congenital glycosylation disorders	1017:1050	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	0	40	theme	whole-exome	13:23	arg1	findings					36:43	Clinical and whole-exome sequencing findings	0:43	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.	0:126	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	8	41	theme	congenital	1017:1026	arg1	disorders					1042:1050	congenital glycosylation disorders	1017:1050	congenital glycosylation disorders	1017:1050	CASE PRESENTATION Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders.
31727010	0	42	from	minority	78:85	arg1	findings					36:43	Clinical and whole-exome sequencing findings	0:43	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.	0:126	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	0	42	from	minority	78:85	arg1	siblings					52:59	two siblings	48:59	two siblings from Hani ethnic minority with congenital glycosylation disorders	48:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	3	43	theme	system	554:559	arg1	involvement					561:571	central nervous system involvement	538:571	central nervous system involvement	538:571	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	4	44	theme	intellectual	655:666	arg1	disability					668:677	intellectual disability	655:677	intellectual disability (ID)	655:682	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	4	44	theme	intellectual	655:666	arg1	symptoms					630:637	The neurological symptoms	613:637	The neurological symptoms of PMM2-CDG	613:649	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	4	44	theme	intellectual	655:666	arg1	ID					680:681	ID	680:681	ID	680:681	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	2	45	theme	PMM2	409:412	arg1	responsible					424:434	responsible	424:434	responsible	424:434	The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate.
31727010	2	45	theme	PMM2	409:412	arg1	loss					401:404	the loss	397:404	the loss	397:404	The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate.
31727010	2	46	theme	mannose	458:464	arg1	phosphate					469:477	mannose 6- phosphate	458:477	mannose 6- phosphate	458:477	The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate.
31727010	12	47	dep	CONCLUSIONS	1417:1427	arg1	This					1429:1432	This	1429:1432	This	1429:1432	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	12	47	dep	CONCLUSIONS	1417:1427	arg1	report					1447:1452	the first report	1437:1452	the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million	1437:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	12	48	with	Yunnan	1565:1570	arg1	population					1579:1588	a population	1577:1588	a population of more than 1 million	1577:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	1	49	theme	CDG	222:224	arg1	series					249:254	a series	247:254	a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans	247:354	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	49	theme	CDG	222:224	arg1	syndromes					226:234	all CDG syndromes	218:234	all CDG syndromes	218:234	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	11	50	theme	Sanger	1345:1350	arg1	sequencing					1352:1361	Sanger sequencing	1345:1361	Sanger sequencing	1345:1361	The mutations were identified in this family by Sanger sequencing and no mutations were detected in the normal control.
31727010	3	51	theme	abnormal	574:581	arg1	coagulation					583:593	abnormal coagulation	574:593	abnormal coagulation	574:593	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	9	52	theme	PMM2	1212:1215	arg1	mutation					1178:1185	previously reported mutation	1158:1185	previously reported mutation (c.395 T > C) in gene of PMM2	1158:1215	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	9	52	theme	PMM2	1212:1215	arg1	variant					1145:1151	c.241-242 del variant	1131:1151	c.241-242 del variant	1131:1151	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	9	52	theme	PMM2	1212:1215	arg1	mutation					1121:1128	one novel mutation	1111:1128	one novel mutation (c.241-242 del variant)	1111:1152	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	9	52	theme	PMM2	1212:1215	arg1	c.395 T > C					1188:1198	c.395 T > C	1188:1198	c.395 T > C	1188:1198	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	12	53	located	found	1551:1555	arg2	groups					1544:1549	five ethnic groups	1532:1549	five ethnic groups found only in Yunnan with a population of more than 1 million	1532:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	12	53	located	found	1551:1555	arg1	Yunnan					1565:1570	Yunnan	1565:1570	Yunnan with a population of more than 1 million	1565:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	1	54	theme	BACKGROUND	128:137	arg1	PMM2-CDG					139:146	BACKGROUND PMM2-CDG,	128:147	PMM2-CDG	139:146	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	54	theme	BACKGROUND	128:137	arg1	disorder					191:198	the most common N-linked glycosylation disorder	152:198	the most common N-linked glycosylation disorder	152:198	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	55	theme	glycoproteins	319:331	arg1	attachment					305:314	attachment	305:314	attachment	305:314	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	1	55	theme	glycoproteins	319:331	arg1	synthesis					291:299	synthesis	291:299	synthesis	291:299	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	12	56	theme	first	1441:1445	arg1	This					1429:1432	This	1429:1432	This	1429:1432	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	12	56	theme	first	1441:1445	arg1	report					1447:1452	the first report	1437:1452	the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million	1437:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	7	57	theme	Chinese	905:911	arg1	population					913:922	the Chinese population	901:922	the Chinese population	901:922	In addition, few CDGs have been reported in the Chinese population.
31727010	12	58	theme	ethnic	1500:1505	arg1	minority					1507:1514	Hani ethnic minority	1495:1514	Hani ethnic minority	1495:1514	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	9	59	theme	novel	1115:1119	arg1	variant					1145:1151	c.241-242 del variant	1131:1151	c.241-242 del variant	1131:1151	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	9	59	theme	novel	1115:1119	arg1	mutation					1121:1128	one novel mutation	1111:1128	one novel mutation (c.241-242 del variant)	1111:1152	Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241-242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2.
31727010	6	60	theme	CDG	801:803	arg1	type					793:796	each type	788:796	each type of CDG	788:803	However, each type of CDG is very rare, and CDGs are problematic to diagnose.
31727010	11	61	located	detected	1385:1392	arg2	mutations					1370:1378	no mutations	1367:1378	no mutations	1367:1378	The mutations were identified in this family by Sanger sequencing and no mutations were detected in the normal control.
31727010	11	61	located	detected	1385:1392	arg1	control					1408:1414	the normal control	1397:1414	the normal control	1397:1414	The mutations were identified in this family by Sanger sequencing and no mutations were detected in the normal control.
31727010	4	62	theme	peripheral	708:717	arg1	neuropathy					719:728	peripheral neuropathy	708:728	peripheral neuropathy	708:728	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	10	63	theme	whole-exome	1273:1283	arg1	sequencing					1285:1294	whole-exome sequencing	1273:1294	whole-exome sequencing	1273:1294	Two mutations were found in proband and her sibling by whole-exome sequencing.
31727010	0	64	theme	Hani	66:69	arg1	minority					78:85	Hani ethnic minority	66:85	Hani ethnic minority with congenital glycosylation disorders	66:125	Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders.
31727010	4	65	theme	PMM2-CDG	642:649	arg1	disability					668:677	intellectual disability	655:677	intellectual disability (ID)	655:682	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	4	65	theme	PMM2-CDG	642:649	arg1	symptoms					630:637	The neurological symptoms	613:637	The neurological symptoms of PMM2-CDG	613:649	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	12	66	theme	groups	1544:1549	arg1	groups					1544:1549	five ethnic groups	1532:1549	five ethnic groups found only in Yunnan with a population of more than 1 million	1532:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	12	66	theme	groups	1544:1549	arg1	one					1525:1527	one	1525:1527	one	1525:1527	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	2	67	theme	PMM2-CDG	374:381	arg1	mutations					361:369	The mutations	357:369	The mutations of PMM2-CDG	357:381	The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate.
31727010	3	68	contain	have	533:536	arg2	involvement					561:571	central nervous system involvement	538:571	central nervous system involvement	538:571	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	3	68	contain	have	533:536	arg2	hepatopathy					600:610	hepatopathy	600:610	hepatopathy	600:610	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	3	68	contain	have	533:536	arg2	coagulation					583:593	abnormal coagulation	574:593	abnormal coagulation	574:593	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	3	68	contain	have	533:536	arg1	patients					510:517	Most patients	505:517	Most patients with PMM2-CDG	505:531	Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy.
31727010	4	69	theme	neurological	617:628	arg1	disability					668:677	intellectual disability	655:677	intellectual disability (ID)	655:682	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	4	69	theme	neurological	617:628	arg1	symptoms					630:637	The neurological symptoms	613:637	The neurological symptoms of PMM2-CDG	613:649	The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy.
31727010	5	70	theme	new	745:747	arg1	cases					753:757	over 100 new CDG cases	736:757	over 100 new CDG cases	736:757	Now, over 100 new CDG cases have been reported.
31727010	1	71	gly	glycoproteins	319:331	arg1	glycoproteins					319:331	glycoproteins	319:331	glycoproteins	319:331	BACKGROUND PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans.
31727010	12	72	from	mutations	1466:1474	arg1	siblings					1483:1490	two siblings	1479:1490	two siblings of Hani ethnic minority	1479:1514	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	12	73	theme	million	1605:1611	arg1	population					1579:1588	a population	1577:1588	a population of more than 1 million	1577:1611	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31727010	12	74	theme	minority	1507:1514	arg1	siblings					1483:1490	two siblings	1479:1490	two siblings of Hani ethnic minority	1479:1514	CONCLUSIONS This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.
31484693	9	0	theme	studies	1744:1750	arg1	consequences					1625:1636	The consequences	1621:1636	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses	1621:1721	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	9	0	theme	studies	1744:1750	arg1	worthy					1727:1732	worthy	1727:1732	worthy of future studies	1727:1750	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	9	1	theme	systemic	1697:1704	arg1	responses					1713:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	9	2	theme	cell-mediated	1673:1685	arg1	responses					1713:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	9	3	theme	immune	1706:1711	arg1	responses					1713:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	7	4	theme	type	1395:1398	arg1	diet					1400:1403	Western type diet	1387:1403	Western type diet	1387:1403	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	1	5	theme	killer	269:274	arg1	cells					285:289	invariant natural killer T (iNKT) cells	251:289	invariant natural killer T (iNKT) cells	251:289	The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells.
31484693	9	6	theme	future	1737:1742	arg1	studies					1744:1750	future studies	1737:1750	future studies	1737:1750	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	4	7	theme	interaction	521:531	arg1	chromatography					533:546	hydrophilic interaction chromatography	509:546	hydrophilic interaction chromatography coupled to MS2	509:561	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	2	8	theme	microbial	347:355	arg1	infections					367:376	microbial and viral infections	347:376	microbial and viral infections	347:376	Thereby, it modulates immune responses against tumors, microbial and viral infections, and autoimmune diseases.
31484693	4	9	theme	intestinal	583:592	arg1	tracts					594:599	murine intestinal tracts	576:599	murine intestinal tracts	576:599	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	4	10	theme	hydrophilic	509:519	arg1	chromatography					533:546	hydrophilic interaction chromatography	509:546	hydrophilic interaction chromatography coupled to MS2	509:561	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	5	11	theme	germ-free	861:869	arg1	mice					871:874	germ-free mice	861:874	germ-free mice	861:874	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	5	11	theme	germ-free	861:869	arg1	microbiota					849:858	microbiota	849:858	microbiota (germ-free mice)	849:875	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	6	12	theme	β-anomeric	1101:1110	arg1	structures					1112:1121	β-anomeric structures	1101:1121	β-anomeric structures	1101:1121	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	8	13	theme	stressful	1561:1569	arg1	conditions					1571:1580	stressful conditions	1561:1580	stressful conditions causing dysbiosis	1561:1598	Collectively, this study suggests that αGalCer is produced by commensals in the mouse intestine and reveals that stressful conditions causing dysbiosis alter its synthesis.
31484693	6	14	contain	contained	947:955	arg2	chain					990:994	a β(R)-hydroxylated hexadecanoyl chain	957:994	a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures	957:1121	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	6	14	contain	contained	947:955	arg2	similar					1128:1134	similar	1128:1134	similar	1128:1134	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	6	14	contain	contained	947:955	arg1	αGalCer					939:945	The identified αGalCer	924:945	The identified αGalCer	924:945	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	6	15	link	N-linked	996:1003	arg1	chain					990:994	a β(R)-hydroxylated hexadecanoyl chain	957:994	a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures	957:1121	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	6	16	theme	cell	1220:1223	arg1	activation					1225:1234	iNKT cell activation	1215:1234	iNKT cell activation	1215:1234	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	1	17	theme	iNKT	279:282	arg1	cells					285:289	invariant natural killer T (iNKT) cells	251:289	invariant natural killer T (iNKT) cells	251:289	The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells.
31484693	6	18	theme	iNKT	1215:1218	arg1	activation					1225:1234	iNKT cell activation	1215:1234	iNKT cell activation	1215:1234	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	3	19	theme	human	466:470	arg1	microbiome					476:485	the human gut microbiome	462:485	the human gut microbiome	462:485	Recently, the production of αGalCer by Bacteroidetes from the human gut microbiome was elucidated.
31484693	7	20	from	production	1286:1295	arg1	mice					1300:1303	mice	1300:1303	mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection	1300:1445	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	3	21	theme	αGalCer	432:438	arg1	production					418:427	the production	414:427	the production of αGalCer by Bacteroidetes from the human gut microbiome	414:485	Recently, the production of αGalCer by Bacteroidetes from the human gut microbiome was elucidated.
31484693	5	22	theme	αGalCer	789:795	arg1	pmol					781:784	1-15 pmol	776:784	1-15 pmol of αGalCer per milligram of protein	776:820	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	6	23	theme	-hydroxylated	963:975	arg1	chain					990:994	a β(R)-hydroxylated hexadecanoyl chain	957:994	a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures	957:1121	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	2	24	theme	autoimmune	383:392	arg1	diseases					394:401	autoimmune diseases	383:401	autoimmune diseases	383:401	Thereby, it modulates immune responses against tumors, microbial and viral infections, and autoimmune diseases.
31484693	0	25	theme	immunogenic	10:20	arg1	α-galactosylceramide					22:41	Bacterial immunogenic α-galactosylceramide	0:41	Bacterial immunogenic α-galactosylceramide	0:41	Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation.
31484693	7	26	theme	Western	1387:1393	arg1	diet					1400:1403	Western type diet	1387:1403	Western type diet	1387:1403	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	6	27	theme	αGalCer	1199:1205	arg1	form					1180:1183	the synthetic form	1166:1183	the synthetic form of the murine αGalCer	1166:1205	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	3	28	from	microbiome	476:485	arg1	Bacteroidetes					443:455	Bacteroidetes	443:455	Bacteroidetes from the human gut microbiome	443:485	Recently, the production of αGalCer by Bacteroidetes from the human gut microbiome was elucidated.
31484693	2	29	theme	immune	314:319	arg1	responses					321:329	immune responses	314:329	immune responses against tumors, microbial and viral infections, and autoimmune diseases	314:401	Thereby, it modulates immune responses against tumors, microbial and viral infections, and autoimmune diseases.
31484693	4	30	theme	different	680:688	arg1	conditions					714:723	different dietary and physiologic conditions	680:723	different dietary and physiologic conditions	680:723	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	0	31	theme	Bacterial	0:8	arg1	α-galactosylceramide					22:41	Bacterial immunogenic α-galactosylceramide	0:41	Bacterial immunogenic α-galactosylceramide	0:41	Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation.
31484693	9	32	theme	altered	1646:1652	arg1	production					1654:1663	this altered production	1641:1663	this altered production	1641:1663	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	6	33	theme	murine	1192:1197	arg1	αGalCer					1199:1205	the murine αGalCer	1188:1205	the murine αGalCer	1188:1205	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	6	34	theme	identified	928:937	arg1	αGalCer					939:945	The identified αGalCer	924:945	The identified αGalCer	924:945	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	5	35	theme	protein	814:820	arg1	milligram					801:809	milligram	801:809	milligram of protein	801:820	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	4	36	theme	murine	576:581	arg1	tracts					594:599	murine intestinal tracts	576:599	murine intestinal tracts	576:599	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	4	37	theme	physiologic	702:712	arg1	conditions					714:723	different dietary and physiologic conditions	680:723	different dietary and physiologic conditions	680:723	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	1	38	theme	antigen-presenting	203:220	arg1	cells					222:226	antigen-presenting cells	203:226	antigen-presenting cells	203:226	The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells.
31484693	0	39	from	dependency	85:94	arg1	inflammation					108:119	inflammation	108:119	inflammation	108:119	Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation.
31484693	0	39	from	dependency	85:94	arg1	diet					99:102	diet	99:102	diet	99:102	Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation.
31484693	6	40	theme	N-linked	996:1003	arg1	chain					990:994	a β(R)-hydroxylated hexadecanoyl chain	957:994	a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures	957:1121	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	1	41	theme	T	276:276	arg1	cells					285:289	invariant natural killer T (iNKT) cells	251:289	invariant natural killer T (iNKT) cells	251:289	The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells.
31484693	0	42	theme	large	68:72	arg1	intestine					74:82	the murine large intestine	57:82	the murine large intestine	57:82	Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation.
31484693	9	43	theme	production	1654:1663	arg1	consequences					1625:1636	The consequences	1621:1636	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses	1621:1721	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	9	43	theme	production	1654:1663	arg1	worthy					1727:1732	worthy	1727:1732	worthy of future studies	1727:1750	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	6	44	theme	Bacteroides	1073:1083	arg1	fragilis					1085:1092	Bacteroides fragilis	1073:1092	Bacteroides fragilis Unlike β-anomeric structures	1073:1121	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	0	45	theme	murine	61:66	arg1	intestine					74:82	the murine large intestine	57:82	the murine large intestine	57:82	Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation.
31484693	7	46	theme	virus	1431:1435	arg1	infection					1437:1445	influenza A virus infection	1419:1445	influenza A virus infection	1419:1445	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	6	47	theme	synthetic	1170:1178	arg1	form					1180:1183	the synthetic form	1166:1183	the synthetic form of the murine αGalCer	1166:1205	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	5	48	theme	fed	881:883	arg1	diet					895:898	fed identical diet	881:898	fed identical diet	881:898	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	3	49	theme	gut	472:474	arg1	microbiome					476:485	the human gut microbiome	462:485	the human gut microbiome	462:485	Recently, the production of αGalCer by Bacteroidetes from the human gut microbiome was elucidated.
31484693	6	50	theme	hexadecanoyl	977:988	arg1	chain					990:994	a β(R)-hydroxylated hexadecanoyl chain	957:994	a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures	957:1121	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	7	51	theme	gut	1361:1363	arg1	microbiota					1365:1374	the gut microbiota	1357:1374	the gut microbiota	1357:1374	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	7	52	theme	influenza	1419:1427	arg1	virus					1431:1435	influenza A virus	1419:1435	influenza A virus infection	1419:1445	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	7	53	theme	microbiota	1365:1374	arg1	composition					1342:1352	the composition	1338:1352	the composition of the gut microbiota	1338:1374	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	4	54	theme	dietary	690:696	arg1	conditions					714:723	different dietary and physiologic conditions	680:723	different dietary and physiologic conditions	680:723	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	5	55	theme	identical	885:893	arg1	diet					895:898	fed identical diet	881:898	fed identical diet	881:898	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	9	56	theme	local	1687:1691	arg1	responses					1713:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	7	57	theme	A	1429:1429	arg1	virus					1431:1435	influenza A virus	1419:1435	influenza A virus infection	1419:1445	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	7	58	theme	αGalCer	1278:1284	arg1	production					1286:1295	αGalCer production	1278:1295	αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection	1278:1445	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	4	59	theme	αGalCer	660:666	arg1	response					668:675	the αGalCer response	656:675	the αGalCer response to different dietary and physiologic conditions	656:723	Using hydrophilic interaction chromatography coupled to MS2, we screened murine intestinal tracts to identify and quantify αGalCers, and we investigated the αGalCer response to different dietary and physiologic conditions.
31484693	1	60	theme	invariant	251:259	arg1	cells					285:289	invariant natural killer T (iNKT) cells	251:289	invariant natural killer T (iNKT) cells	251:289	The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells.
31484693	5	61	theme	mice	761:764	arg1	cecum					738:742	the cecum	734:742	the cecum	734:742	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	5	61	theme	mice	761:764	arg1	colon					752:756	the colon	748:756	the colon of mice	748:764	In both the cecum and the colon of mice, we found 1-15 pmol of αGalCer per milligram of protein; in contrast, mice lacking microbiota (germ-free mice) and fed identical diet did not harbor αGalCer.
31484693	9	62	from	consequences	1625:1636	arg1	responses					1713:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	iNKT cell-mediated local and systemic immune responses	1668:1721	The consequences of this altered production on iNKT cell-mediated local and systemic immune responses are worthy of future studies.
31484693	8	63	theme	mouse	1528:1532	arg1	intestine					1534:1542	the mouse intestine	1524:1542	the mouse intestine	1524:1542	Collectively, this study suggests that αGalCer is produced by commensals in the mouse intestine and reveals that stressful conditions causing dysbiosis alter its synthesis.
31484693	7	64	from	decrease	1266:1273	arg1	production					1286:1295	αGalCer production	1278:1295	αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection	1278:1445	Last, we observed a decrease in αGalCer production in mice exposed to conditions that alter the composition of the gut microbiota, including Western type diet, colitis, and influenza A virus infection.
31484693	2	65	theme	viral	361:365	arg1	infections					367:376	microbial and viral infections	347:376	microbial and viral infections	347:376	Thereby, it modulates immune responses against tumors, microbial and viral infections, and autoimmune diseases.
31484693	6	66	from	fragilis	1156:1163	arg1	αGalCers					1139:1146	αGalCers	1139:1146	αGalCers from B. fragilis	1139:1163	The identified αGalCer contained a β(R)-hydroxylated hexadecanoyl chain N-linked to C18-sphinganine, which differed from what has been reported with Bacteroides fragilis Unlike β-anomeric structures, but similar to αGalCers from B. fragilis, the synthetic form of the murine αGalCer induced iNKT cell activation in vitro.
31484693	1	67	theme	natural	261:267	arg1	cells					285:289	invariant natural killer T (iNKT) cells	251:289	invariant natural killer T (iNKT) cells	251:289	The glycosphingolipid, α-galactosylceramide (αGalCer), when presented by CD1d on antigen-presenting cells, efficiently activates invariant natural killer T (iNKT) cells.
31178836	9	0	theme	neutralizing	1922:1933	arg1	responses					1944:1952	broadly neutralizing antibody responses	1914:1952	broadly neutralizing antibody responses	1914:1952	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	9	1	theme	V1	1801:1802	arg1	sequences					1804:1812	short V1 sequences	1795:1812	short V1 sequences	1795:1812	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	3	2	theme	Env	675:677	arg1	clones					679:684	68 functionally Env clones	659:684	68 functionally Env clones	659:684	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	1	3	theme	neutralizing	247:258	arg1	activity					260:267	broadly neutralizing activity	239:267	broadly neutralizing activity	239:267	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	4	4	theme	time	855:858	arg1	points					860:865	different time points	845:865	different time points	845:865	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	9	5	from	sequences	1804:1812	arg1	V1					1866:1867	V1	1866:1867	V1	1866:1867	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	5	6	theme	last	1120:1123	arg1	points					1130:1135	the last time points	1116:1135	the last time points	1116:1135	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	7	7	with	consistent	1518:1527	arg1	variations					1549:1558	higher residue variations	1534:1558	higher residue variations at the antibody recognition sites	1534:1592	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	9	8	theme	potential	1823:1831	arg1	PNGS					1857:1860	PNGS	1857:1860	PNGS	1857:1860	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	9	8	theme	potential	1823:1831	arg1	glycosylation					1842:1854	less potential N-linked glycosylation	1818:1854	less potential N-linked glycosylation (PNGS)	1818:1861	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	4	9	theme	Env	831:833	arg1	clones					835:840	Env clones	831:840	Env clones of different time points	831:865	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	0	10	theme	Infected	65:72	arg1	Patient					74:80	a Chinese Chronically HIV-1 Infected Patient	37:80	a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity	37:115	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	9	11	from	diversity	1784:1792	arg1	V1					1866:1867	V1	1866:1867	V1	1866:1867	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	1	12	theme	gene	189:192	arg1	characteristics					132:146	the characteristics	128:146	the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual	128:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	4	13	theme	HIV-1	891:895	arg1	sequences					911:919	165 Chinese HIV-1 subtype B env sequences	879:919	165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database)	879:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	6	14	theme	neutralization	1206:1219	arg1	assay					1221:1225	a neutralization assay	1204:1225	a neutralization assay	1204:1225	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	5	15	theme	lower	1017:1021	arg1	ratio					1023:1027	a lower ratio	1015:1027	a lower ratio of NXT	1015:1034	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	1	16	theme	HIV-1	207:211	arg1	individual					222:231	a natural HIV-1 infected individual	197:231	a natural HIV-1 infected individual	197:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	7	17	theme	higher	1534:1539	arg1	variations					1549:1558	higher residue variations	1534:1558	higher residue variations at the antibody recognition sites	1534:1592	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	7	18	from	sites	1588:1592	arg1	variations					1549:1558	higher residue variations	1534:1558	higher residue variations at the antibody recognition sites	1534:1592	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	3	19	theme	points	745:750	arg1	plasma					726:731	the plasma	722:731	the plasma of six time points spanning over 5 years in this donor	722:786	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	6	20	theme	sequence	1182:1189	arg1	analysis					1191:1198	A sequence analysis	1180:1198	A sequence analysis	1180:1198	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	5	21	theme	potential	994:1002	arg1	glycan					1004:1009	less potential glycan	989:1009	less potential glycan	989:1009	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	3	22	theme	length	616:621	arg1	fragments					638:646	155 full length HIV-1 env gene fragments	607:646	155 full length HIV-1 env gene fragments (including 68 functionally Env clones)	607:685	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	2	23	theme	VRC01-class	508:518	arg1	antibody					533:540	a VRC01-class neutralizing antibody	506:540	a VRC01-class neutralizing antibody DRVIA7 (A7)	506:552	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	6	24	theme	env	1288:1290	arg1	sequences					1292:1300	env sequences	1288:1300	env sequences in the patient	1288:1315	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	1	25	theme	HIV-1	155:159	arg1	env					184:186	env	184:186	env	184:186	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	1	25	theme	HIV-1	155:159	arg1	glycoprotein					170:181	HIV-1 envelope glycoprotein	155:181	the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual	151:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	7	26	theme	autologous	1495:1504	arg1	plasma					1506:1511	the concurrent autologous plasma	1480:1511	the concurrent autologous plasma	1480:1511	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	1	27	from	individual	222:231	arg1	characteristics					132:146	the characteristics	128:146	the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual	128:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	5	28	from	glycan	1004:1009	arg1	gp160					1044:1048	gp160	1044:1048	gp160	1044:1048	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	1	29	theme	antibodies	339:348	arg1	generation					299:308	the generation	295:308	the generation of such broadly neutralizing antibodies	295:348	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	1	30	theme	glycoprotein	170:181	arg1	gene					189:192	the HIV-1 envelope glycoprotein (env) gene	151:192	the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual	151:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	1	31	theme	infected	213:220	arg1	individual					222:231	a natural HIV-1 infected individual	197:231	a natural HIV-1 infected individual	197:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	4	32	theme	B	905:905	arg1	sequences					911:919	165 Chinese HIV-1 subtype B env sequences	879:919	165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database)	879:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	1	33	dep	provide	274:280	arg1	Exploring					118:126	Exploring	118:126	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual	118:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	0	34	theme	Broadly	87:93	arg1	Activity					108:115	Broadly Neutralizing Activity	87:115	Broadly Neutralizing Activity	87:115	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	2	35	theme	antibody	533:540	arg1	A7					550:551	A7	550:551	A7	550:551	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	2	35	theme	antibody	533:540	arg1	DRVIA7					542:547	a VRC01-class neutralizing antibody DRVIA7	506:547	a VRC01-class neutralizing antibody DRVIA7 (A7)	506:552	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	9	36	theme	antibody	1935:1942	arg1	responses					1944:1952	broadly neutralizing antibody responses	1914:1952	broadly neutralizing antibody responses	1914:1952	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	1	37	from	characteristics	132:146	arg1	individual					222:231	a natural HIV-1 infected individual	197:231	a natural HIV-1 infected individual	197:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	4	38	theme	HIV	926:928	arg1	B_database					957:966	Chinese B_database	949:966	Chinese B_database	949:966	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	4	38	theme	HIV	926:928	arg1	Database					939:946	HIV Sequence Database	926:946	HIV Sequence Database (Chinese B_database)	926:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	5	39	from	NXS	1037:1039	arg1	gp160					1044:1048	gp160	1044:1048	gp160	1044:1048	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	40	theme	time	1082:1085	arg1	points					1087:1092	the first five time points	1067:1092	the first five time points compared to that from the last time points, as well that from the Chinese B_database	1067:1177	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	2	41	theme	infected	433:440	arg1	patient					442:448	a chronically HIV-1 infected patient	413:448	a chronically HIV-1 infected patient with broadly neutralization activity	413:485	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	0	42	theme	Envelope	19:26	arg1	Genes					28:32	Envelope Genes	19:32	Envelope Genes	19:32	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	7	43	theme	antibody	1567:1574	arg1	sites					1588:1592	the antibody recognition sites	1563:1592	the antibody recognition sites	1563:1592	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	4	44	theme	Chinese	949:955	arg1	B_database					957:966	Chinese B_database	949:966	Chinese B_database	949:966	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	4	44	theme	Chinese	949:955	arg1	Database					939:946	HIV Sequence Database	926:946	HIV Sequence Database (Chinese B_database)	926:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	4	45	theme	Viral	789:793	arg1	features					795:802	Viral features	789:802	Viral features	789:802	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	5	46	theme	Shorter	970:976	arg1	length					981:986	Shorter V1 length	970:986	Shorter V1 length	970:986	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	2	47	theme	neutralization	463:476	arg1	activity					478:485	broadly neutralization activity	455:485	broadly neutralization activity	455:485	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	3	48	theme	env	629:631	arg1	fragments					638:646	155 full length HIV-1 env gene fragments	607:646	155 full length HIV-1 env gene fragments (including 68 functionally Env clones)	607:685	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	8	49	from	plasmas	1623:1629	arg1	viruses					1606:1612	Almost all viruses	1595:1612	Almost all viruses from the plasmas	1595:1629	Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies.
31178836	0	50	theme	Chinese	39:45	arg1	Patient					74:80	a Chinese Chronically HIV-1 Infected Patient	37:80	a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity	37:115	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	5	51	theme	first	1071:1075	arg1	points					1087:1092	the first five time points	1067:1092	the first five time points compared to that from the last time points, as well that from the Chinese B_database	1067:1177	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	9	52	theme	greater	1770:1776	arg1	diversity					1784:1792	greater viral diversity	1770:1792	greater viral diversity	1770:1792	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	5	53	theme	time	1125:1128	arg1	points					1130:1135	the last time points	1116:1135	the last time points	1116:1135	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	7	54	theme	potent	1397:1402	arg1	activity					1419:1426	The potent neutralization activity	1393:1426	The potent neutralization activity	1393:1426	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	7	54	theme	potent	1397:1402	arg1	consistent					1518:1527	consistent	1518:1527	consistent	1518:1527	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	9	55	theme	infected	1721:1728	arg1	individual					1730:1739	a chronically HIV-1 infected individual	1701:1739	a chronically HIV-1 infected individual over 10 years	1701:1753	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	6	56	theme	lineage	1373:1379	arg1	antibodies					1381:1390	A7 lineage antibodies	1370:1390	A7 lineage antibodies	1370:1390	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	0	57	dep	Characteristics	0:14	arg1	Patient					74:80	a Chinese Chronically HIV-1 Infected Patient	37:80	a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity	37:115	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	9	58	theme	short	1795:1799	arg1	sequences					1804:1812	short V1 sequences	1795:1812	short V1 sequences	1795:1812	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	6	59	from	diversity	1275:1283	arg1	patient					1309:1315	the patient	1305:1315	the patient	1305:1315	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	0	60	with	Patient	74:80	arg1	Activity					108:115	Broadly Neutralizing Activity	87:115	Broadly Neutralizing Activity	87:115	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	9	61	link	N-linked	1833:1840	arg1	PNGS					1857:1860	PNGS	1857:1860	PNGS	1857:1860	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	9	61	link	N-linked	1833:1840	arg1	glycosylation					1842:1854	less potential N-linked glycosylation	1818:1854	less potential N-linked glycosylation (PNGS)	1818:1861	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	4	62	theme	different	845:853	arg1	points					860:865	different time points	845:865	different time points	845:865	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	9	63	theme	N-linked	1833:1840	arg1	PNGS					1857:1860	PNGS	1857:1860	PNGS	1857:1860	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	9	63	theme	N-linked	1833:1840	arg1	glycosylation					1842:1854	less potential N-linked glycosylation	1818:1854	less potential N-linked glycosylation (PNGS)	1818:1861	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	6	64	from	sequences	1292:1300	arg1	patient					1309:1315	the patient	1305:1315	the patient	1305:1315	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	5	65	dep	well	1141:1144	arg1	that					1146:1149	that	1146:1149	that	1146:1149	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	3	66	theme	time	740:743	arg1	points					745:750	six time points	736:750	six time points spanning over 5 years in this donor	736:786	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	6	67	theme	Env-pseudoviruses	1230:1246	arg1	assay					1221:1225	a neutralization assay	1204:1225	a neutralization assay	1204:1225	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	6	67	theme	Env-pseudoviruses	1230:1246	arg1	analysis					1191:1198	A sequence analysis	1180:1198	A sequence analysis	1180:1198	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	2	68	attach	isolated	558:565	arg2	A7					550:551	A7	550:551	A7	550:551	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	2	68	attach	isolated	558:565	arg2	DRVIA7					542:547	a VRC01-class neutralizing antibody DRVIA7	506:547	a VRC01-class neutralizing antibody DRVIA7 (A7)	506:552	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	2	68	attach	isolated	558:565	arg1	patient					576:582	the patient	572:582	the patient	572:582	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	7	69	theme	residue	1541:1547	arg1	variations					1549:1558	higher residue variations	1534:1558	higher residue variations at the antibody recognition sites	1534:1592	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	9	70	gly	glycosylation	1842:1854	arg1	V1					1866:1867	V1	1866:1867	V1	1866:1867	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	1	71	theme	appropriate	380:390	arg1	immunogen					392:400	an appropriate immunogen	377:400	an appropriate immunogen	377:400	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	3	72	theme	present	592:598	arg1	study					600:604	the present study	588:604	the present study	588:604	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	1	73	theme	natural	199:205	arg1	individual					222:231	a natural HIV-1 infected individual	197:231	a natural HIV-1 infected individual	197:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	4	74	theme	Chinese	883:889	arg1	sequences					911:919	165 Chinese HIV-1 subtype B env sequences	879:919	165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database)	879:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	6	75	theme	increasing	1264:1273	arg1	consistent					1321:1330	consistent	1321:1330	consistent	1321:1330	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	6	75	theme	increasing	1264:1273	arg1	diversity					1275:1283	the increasing diversity	1260:1283	the increasing diversity of env sequences in the patient	1260:1315	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	8	76	theme	lineage	1677:1683	arg1	antibodies					1685:1694	lineage antibodies	1677:1694	lineage antibodies	1677:1694	Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies.
31178836	4	77	theme	points	860:865	arg1	sequences					911:919	165 Chinese HIV-1 subtype B env sequences	879:919	165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database)	879:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	4	77	theme	points	860:865	arg1	clones					835:840	Env clones	831:840	Env clones of different time points	831:865	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	5	78	theme	Chinese	1160:1166	arg1	B_database					1168:1177	the Chinese B_database	1156:1177	the Chinese B_database	1156:1177	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	1	79	gly	glycoprotein	170:181	arg1	env					184:186	env	184:186	env	184:186	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	1	79	gly	glycoprotein	170:181	arg1	glycoprotein					170:181	HIV-1 envelope glycoprotein	155:181	the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual	151:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	3	80	theme	full	611:614	arg1	fragments					638:646	155 full length HIV-1 env gene fragments	607:646	155 full length HIV-1 env gene fragments (including 68 functionally Env clones)	607:685	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	2	81	with	patient	442:448	arg1	activity					478:485	broadly neutralization activity	455:485	broadly neutralization activity	455:485	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	5	82	located	observed	1055:1062	arg2	length					981:986	Shorter V1 length	970:986	Shorter V1 length	970:986	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	82	located	observed	1055:1062	arg1	points					1087:1092	the first five time points	1067:1092	the first five time points compared to that from the last time points, as well that from the Chinese B_database	1067:1177	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	82	located	observed	1055:1062	arg2	glycan					1004:1009	less potential glycan	989:1009	less potential glycan	989:1009	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	82	located	observed	1055:1062	arg2	ratio					1023:1027	a lower ratio	1015:1027	a lower ratio of NXT	1015:1034	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	82	located	observed	1055:1062	arg2	NXS					1037:1039	NXS	1037:1039	NXS	1037:1039	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	7	83	theme	plasma	1506:1511	arg1	neutralization					1462:1475	the neutralization	1458:1475	the neutralization of the concurrent autologous plasma	1458:1511	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	9	84	from	glycosylation	1842:1854	arg1	V1					1866:1867	V1	1866:1867	V1	1866:1867	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	5	85	from	length	981:986	arg1	gp160					1044:1048	gp160	1044:1048	gp160	1044:1048	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	6	86	theme	sequences	1292:1300	arg1	consistent					1321:1330	consistent	1321:1330	consistent	1321:1330	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	6	86	theme	sequences	1292:1300	arg1	diversity					1275:1283	the increasing diversity	1260:1283	the increasing diversity of env sequences in the patient	1260:1315	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	6	87	from	patient	1309:1315	arg1	consistent					1321:1330	consistent	1321:1330	consistent	1321:1330	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	6	87	from	patient	1309:1315	arg1	diversity					1275:1283	the increasing diversity	1260:1283	the increasing diversity of env sequences in the patient	1260:1315	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	1	88	from	gene	189:192	arg1	individual					222:231	a natural HIV-1 infected individual	197:231	a natural HIV-1 infected individual	197:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	7	89	theme	concurrent	1484:1493	arg1	plasma					1506:1511	the concurrent autologous plasma	1480:1511	the concurrent autologous plasma	1480:1511	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	4	90	from	Database	939:946	arg1	sequences					911:919	165 Chinese HIV-1 subtype B env sequences	879:919	165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database)	879:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	4	90	from	Database	939:946	arg1	clones					835:840	Env clones	831:840	Env clones of different time points	831:865	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	5	91	from	ratio	1023:1027	arg1	gp160					1044:1048	gp160	1044:1048	gp160	1044:1048	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	1	92	theme	neutralizing	326:337	arg1	antibodies					339:348	such broadly neutralizing antibodies	313:348	such broadly neutralizing antibodies	313:348	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	1	93	theme	envelope	161:168	arg1	env					184:186	env	184:186	env	184:186	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	1	93	theme	envelope	161:168	arg1	glycoprotein					170:181	HIV-1 envelope glycoprotein	155:181	the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual	151:231	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	4	94	theme	Sequence	930:937	arg1	B_database					957:966	Chinese B_database	949:966	Chinese B_database	949:966	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	4	94	theme	Sequence	930:937	arg1	Database					939:946	HIV Sequence Database	926:946	HIV Sequence Database (Chinese B_database)	926:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	0	95	theme	Neutralizing	95:106	arg1	Activity					108:115	Broadly Neutralizing Activity	87:115	Broadly Neutralizing Activity	87:115	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	6	96	with	consistent	1321:1330	arg1	maturation					1356:1365	maturation	1356:1365	maturation	1356:1365	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	6	96	with	consistent	1321:1330	arg1	appearance					1341:1350	appearance	1341:1350	appearance	1341:1350	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	4	97	theme	subtype	897:903	arg1	sequences					911:919	165 Chinese HIV-1 subtype B env sequences	879:919	165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database)	879:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	8	98	dep	VRC01	1664:1668	arg1	antibodies					1685:1694	lineage antibodies	1677:1694	lineage antibodies	1677:1694	Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies.
31178836	5	99	theme	NXT	1032:1034	arg1	ratio					1023:1027	a lower ratio	1015:1027	a lower ratio of NXT	1015:1034	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	99	theme	NXT	1032:1034	arg1	NXS					1037:1039	NXS	1037:1039	NXS	1037:1039	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	99	theme	NXT	1032:1034	arg1	glycan					1004:1009	less potential glycan	989:1009	less potential glycan	989:1009	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	5	99	theme	NXT	1032:1034	arg1	length					981:986	Shorter V1 length	970:986	Shorter V1 length	970:986	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	4	100	theme	env	907:909	arg1	sequences					911:919	165 Chinese HIV-1 subtype B env sequences	879:919	165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database)	879:967	Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database).
31178836	9	101	theme	responses	1944:1952	arg1	development					1899:1909	the development	1895:1909	the development of broadly neutralizing antibody responses	1895:1952	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	0	102	theme	Genes	28:32	arg1	Characteristics					0:14	Characteristics	0:14	Characteristics of Envelope Genes	0:32	Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity.
31178836	3	103	theme	gene	633:636	arg1	fragments					638:646	155 full length HIV-1 env gene fragments	607:646	155 full length HIV-1 env gene fragments (including 68 functionally Env clones)	607:685	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	7	104	theme	recognition	1576:1586	arg1	sites					1588:1592	the antibody recognition sites	1563:1592	the antibody recognition sites	1563:1592	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	3	105	theme	HIV-1	623:627	arg1	fragments					638:646	155 full length HIV-1 env gene fragments	607:646	155 full length HIV-1 env gene fragments (including 68 functionally Env clones)	607:685	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31178836	2	106	theme	neutralizing	520:531	arg1	antibody					533:540	a VRC01-class neutralizing antibody	506:540	a VRC01-class neutralizing antibody DRVIA7 (A7)	506:552	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	5	107	theme	V1	978:979	arg1	length					981:986	Shorter V1 length	970:986	Shorter V1 length	970:986	Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database.
31178836	2	108	theme	broadly	455:461	arg1	activity					478:485	broadly neutralization activity	455:485	broadly neutralization activity	455:485	Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient.
31178836	1	109	theme	immunogen	392:400	arg1	design					367:372	the design	363:372	the design of an appropriate immunogen	363:400	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	1	110	theme	such	313:316	arg1	antibodies					339:348	such broadly neutralizing antibodies	313:348	such broadly neutralizing antibodies	313:348	Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen.
31178836	6	111	dep	appearance	1341:1350	arg1	the					1337:1339	the	1337:1339	the	1337:1339	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	9	112	theme	viral	1778:1782	arg1	diversity					1784:1792	greater viral diversity	1770:1792	greater viral diversity	1770:1792	For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.
31178836	6	113	theme	antibodies	1381:1390	arg1	maturation					1356:1365	maturation	1356:1365	maturation	1356:1365	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	6	113	theme	antibodies	1381:1390	arg1	appearance					1341:1350	appearance	1341:1350	appearance	1341:1350	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	7	114	theme	neutralization	1404:1417	arg1	activity					1419:1426	The potent neutralization activity	1393:1426	The potent neutralization activity	1393:1426	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	7	114	theme	neutralization	1404:1417	arg1	consistent					1518:1527	consistent	1518:1527	consistent	1518:1527	The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites.
31178836	8	115	theme	all	1602:1604	arg1	viruses					1606:1612	Almost all viruses	1595:1612	Almost all viruses from the plasmas	1595:1629	Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies.
31178836	6	116	theme	A7	1370:1371	arg1	antibodies					1381:1390	A7 lineage antibodies	1370:1390	A7 lineage antibodies	1370:1390	A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies.
31178836	3	117	dep	fragments	638:646	arg1	including					649:657	including	649:657	including 68 functionally Env clones	649:684	In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor.
31063103	5	0	theme	significant	641:651	arg1	differences					653:663	No significant differences	638:663	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes	638:731	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	5	1	theme	baseline	681:688	arg1	counts					702:707	baseline CD4+ T-cell counts	681:707	baseline CD4+ T-cell counts	681:707	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	6	2	theme	CCR5	1012:1015	arg1	co-receptor					1017:1027	CCR5 co-receptor	1012:1027	CCR5 co-receptor	1012:1027	The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor.
31063103	8	3	theme	predicted	1162:1170	arg1	site					1195:1198	The predicted N-linked glycosylation site	1158:1198	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region	1158:1243	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	0	4	from	tropism	12:18	arg1	variants					69:76	variants	69:76	variants of antiretroviral-naive HIV-1 infected subjects	69:124	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	3	5	theme	%	539:539	arg1	rate					529:532	a false-positive rate	512:532	a false-positive rate of 10%	512:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	0	6	theme	HIV-1	102:106	arg1	subjects					117:124	antiretroviral-naive HIV-1 infected subjects	81:124	antiretroviral-naive HIV-1 infected subjects	81:124	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	9	7	theme	viral	1434:1438	arg1	tropism					1440:1446	both viral tropism	1429:1446	both viral tropism	1429:1446	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	3	8	theme	co-receptor	409:419	arg1	tropism					421:427	the co-receptor tropism	405:427	the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%	405:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	9	9	theme	variable	1311:1318	arg1	motifs					1326:1331	variable crown motifs	1311:1331	variable crown motifs	1311:1331	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	9	10	theme	CCR5	1355:1358	arg1	viruses					1370:1376	both CCR5 and CXCR4 viruses	1350:1376	both CCR5 and CXCR4 viruses	1350:1376	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	0	11	theme	antiretroviral-naive	81:100	arg1	subjects					117:124	antiretroviral-naive HIV-1 infected subjects	81:124	antiretroviral-naive HIV-1 infected subjects	81:124	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	6	12	theme	more	904:907	arg1	CXCR4-use					909:917	a significantly more CXCR4-use	888:917	a significantly more CXCR4-use	888:917	The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor.
31063103	7	13	theme	CCR5	1117:1120	arg1	viruses					1122:1128	CCR5 viruses	1117:1128	CCR5 viruses	1117:1128	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	9	14	located	observed	1338:1345	arg1	genotypes					1463:1471	almost all genotypes	1452:1471	almost all genotypes identified in this study except subtype B	1452:1513	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	9	14	located	observed	1338:1345	arg1	viruses					1370:1376	both CCR5 and CXCR4 viruses	1350:1376	both CCR5 and CXCR4 viruses	1350:1376	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	9	14	located	observed	1338:1345	arg2	motifs					1326:1331	variable crown motifs	1311:1331	variable crown motifs	1311:1331	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	9	15	theme	all	1459:1461	arg1	genotypes					1463:1471	almost all genotypes	1452:1471	almost all genotypes identified in this study except subtype B	1452:1513	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	4	16	theme	CCR5-tropic	604:614	arg1	virus					616:620	the CCR5-tropic virus	600:620	the CCR5-tropic virus	600:620	Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85).
31063103	0	17	theme	subjects	117:124	arg1	variants					69:76	variants	69:76	variants of antiretroviral-naive HIV-1 infected subjects	69:124	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	7	18	theme	CXCR4	1098:1102	arg1	viruses					1104:1110	the CXCR4 viruses	1094:1110	the CXCR4 viruses	1094:1110	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	10	19	theme	clinical	1568:1575	arg1	practice					1577:1584	clinical practice	1568:1584	clinical practice	1568:1584	These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.
31063103	3	20	theme	antiretroviral-naive	453:472	arg1	patients					474:481	85 antiretroviral-naive patients	450:481	85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%	450:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	0	21	theme	infected	108:115	arg1	subjects					117:124	antiretroviral-naive HIV-1 infected subjects	81:124	antiretroviral-naive HIV-1 infected subjects	81:124	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	5	22	theme	CXCR4-tropic	778:789	arg1	virus					806:810	CXCR4-tropic or CCR5-tropic virus	778:810	CXCR4-tropic or CCR5-tropic virus	778:810	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	2	23	theme	tropism	299:305	arg1	important					310:318	important	310:318	important	310:318	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	2	23	theme	tropism	299:305	arg1	investigation					270:282	A molecular epidemiology investigation	245:282	A molecular epidemiology investigation of co-receptor tropism	245:305	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	1	24	theme	HIV-1	185:189	arg1	transmission					191:202	HIV-1 transmission	185:202	HIV-1 transmission	185:202	Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients.
31063103	0	25	from	characteristics	32:46	arg1	variants					69:76	variants	69:76	variants of antiretroviral-naive HIV-1 infected subjects	69:124	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	8	26	gly	glycosylation	1181:1193	arg2	site					1195:1198	The predicted N-linked glycosylation site	1158:1198	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region	1158:1243	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	2	27	theme	effective	346:354	arg1	control					356:362	effective control	346:362	effective control	346:362	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	0	28	theme	Co-receptor	0:10	arg1	tropism					12:18	Co-receptor tropism	0:18	Co-receptor tropism	0:18	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	6	29	theme	CRF01_AE	936:943	arg1	infections					945:954	CRF01_AE infections	936:954	CRF01_AE infections	936:954	The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor.
31063103	3	30	from	rate	529:532	arg1	algorithm					499:507	Geno2pheno algorithm	488:507	Geno2pheno algorithm at a false-positive rate of 10%	488:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	0	31	theme	genetic	24:30	arg1	characteristics					32:46	genetic characteristics	24:46	genetic characteristics	24:46	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	5	32	theme	CD4+	690:693	arg1	counts					702:707	baseline CD4+ T-cell counts	681:707	baseline CD4+ T-cell counts	681:707	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	8	33	link	N-linked	1172:1179	arg1	site					1195:1198	The predicted N-linked glycosylation site	1158:1198	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region	1158:1243	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	5	34	theme	CCR5-tropic	794:804	arg1	virus					806:810	CXCR4-tropic or CCR5-tropic virus	778:810	CXCR4-tropic or CCR5-tropic virus	778:810	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	9	35	theme	subtype	1505:1511	arg1	B					1513:1513	subtype B	1505:1513	subtype B	1505:1513	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	9	36	theme	crown	1320:1324	arg1	motifs					1326:1331	variable crown motifs	1311:1331	variable crown motifs	1311:1331	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	4	37	theme	subjects	581:588	arg1	majority					565:572	a majority	563:572	a majority of the subjects	563:588	Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85).
31063103	5	38	theme	T-cell	695:700	arg1	counts					702:707	baseline CD4+ T-cell counts	681:707	baseline CD4+ T-cell counts	681:707	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	8	39	theme	glycosylation	1181:1193	arg1	site					1195:1198	The predicted N-linked glycosylation site	1158:1198	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region	1158:1243	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	2	40	theme	clinical	324:331	arg1	practice					333:340	clinical practice	324:340	clinical practice	324:340	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	1	41	theme	disease	212:218	arg1	progression					220:230	the disease progression	208:230	the disease progression in patients	208:242	Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients.
31063103	3	42	theme	HIV-1	432:436	arg1	variants					438:445	HIV-1 variants	432:445	HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%	432:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	2	43	theme	HIV-1	367:371	arg1	practice					333:340	clinical practice	324:340	clinical practice	324:340	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	2	43	theme	HIV-1	367:371	arg1	control					356:362	effective control	346:362	effective control	346:362	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	7	44	theme	higher	1066:1071	arg1	charge					1084:1089	a higher median net charge	1064:1089	a higher median net charge	1064:1089	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	6	45	theme	virus	872:876	arg1	genotype					878:885	the virus genotype	868:885	the virus genotype	868:885	The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor.
31063103	2	46	theme	molecular	247:255	arg1	important					310:318	important	310:318	important	310:318	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	2	46	theme	molecular	247:255	arg1	investigation					270:282	A molecular epidemiology investigation	245:282	A molecular epidemiology investigation of co-receptor tropism	245:305	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	8	47	theme	V3	1235:1236	arg1	region					1238:1243	the V3 region	1231:1243	the V3 region	1231:1243	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	8	48	theme	amino	1208:1212	arg1	acids					1214:1218	amino acids 6 and 8	1208:1226	acids	1214:1218	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	7	49	theme	median	1073:1078	arg1	charge					1084:1089	a higher median net charge	1064:1089	a higher median net charge	1064:1089	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	7	50	theme	V3	1052:1053	arg1	analysis					1040:1047	Sequences analysis	1030:1047	Sequences analysis of V3	1030:1053	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	1	51	from	progression	220:230	arg1	patients					235:242	patients	235:242	patients	235:242	Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients.
31063103	3	52	theme	Geno2pheno	488:497	arg1	algorithm					499:507	Geno2pheno algorithm	488:507	Geno2pheno algorithm at a false-positive rate of 10%	488:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	0	53	theme	V3	55:56	arg1	regions					58:64	the V3 regions	51:64	the V3 regions	51:64	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	5	54	theme	transmission	713:724	arg1	routes					726:731	transmission routes	713:731	transmission routes	713:731	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	7	55	dep	revealed	1055:1062	arg1	3.0					1139:1141	3.0	1139:1141	3.0	1139:1141	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	7	55	dep	revealed	1055:1062	arg1	4.0					1131:1133	4.0	1131:1133	4.0	1131:1133	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	7	55	dep	revealed	1055:1062	arg1	P					1144:1144	P	1144:1144	P &lt; 0.05	1144:1154	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	4	56	dep	harboured	590:598	arg1	69/85					630:634	69/85	630:634	69/85	630:634	Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85).
31063103	4	56	dep	harboured	590:598	arg1	%					627:627	81.2%	623:627	81.2%	623:627	Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85).
31063103	9	57	theme	CXCR4	1364:1368	arg1	viruses					1370:1376	both CCR5 and CXCR4 viruses	1350:1376	both CCR5 and CXCR4 viruses	1350:1376	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	9	58	theme	motif	1407:1411	arg1	GPGQ					1413:1416	the most prevalent motif GPGQ	1388:1416	the most prevalent motif GPGQ	1388:1416	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	7	59	theme	net	1080:1082	arg1	charge					1084:1089	a higher median net charge	1064:1089	a higher median net charge	1064:1089	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	10	60	theme	biology	1625:1631	arg1	understanding					1602:1614	our understanding	1598:1614	our understanding of HIV-1 biology	1598:1631	These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.
31063103	8	61	from	acids	1214:1218	arg1	region					1238:1243	the V3 region	1231:1243	the V3 region	1231:1243	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	1	62	theme	Co-receptor	127:137	arg1	tropism					139:145	Co-receptor tropism	127:145	Co-receptor tropism	127:145	Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients.
31063103	5	63	from	differences	653:663	arg1	routes					726:731	transmission routes	713:731	transmission routes	713:731	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	5	63	from	differences	653:663	arg1	counts					702:707	baseline CD4+ T-cell counts	681:707	baseline CD4+ T-cell counts	681:707	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	5	63	from	differences	653:663	arg1	age					676:678	age	676:678	age	676:678	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	5	63	from	differences	653:663	arg1	gender					668:673	gender	668:673	gender	668:673	No significant differences in gender, age, baseline CD4+ T-cell counts and transmission routes were observed between subjects infected with CXCR4-tropic or CCR5-tropic virus.
31063103	10	64	theme	important	1541:1549	arg1	implications					1551:1562	important implications	1541:1562	important implications for clinical practice	1541:1584	These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.
31063103	2	65	theme	co-receptor	287:297	arg1	tropism					299:305	co-receptor tropism	287:305	co-receptor tropism	287:305	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	6	66	theme	co-receptor	817:827	arg1	tropism					829:835	The co-receptor tropism	813:835	The co-receptor tropism	813:835	The co-receptor tropism appeared to be associated with the virus genotype; a significantly more CXCR4-use was predicted in CRF01_AE infections whereas all CRF07_BC and CRF08_BC were predicted to use CCR5 co-receptor.
31063103	10	67	theme	HIV-1	1619:1623	arg1	biology					1625:1631	HIV-1 biology	1619:1631	HIV-1 biology	1619:1631	These findings may offer important implications for clinical practice and enhance our understanding of HIV-1 biology.
31063103	8	68	theme	CXCR4	1287:1291	arg1	viruses					1293:1299	CXCR4 viruses	1287:1299	CXCR4 viruses	1287:1299	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	4	69	theme	81.2	623:626	arg1	69/85					630:634	69/85	630:634	69/85	630:634	Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85).
31063103	4	69	theme	81.2	623:626	arg1	%					627:627	81.2%	623:627	81.2%	623:627	Our data showed that a majority of the subjects harboured the CCR5-tropic virus (81.2%, 69/85).
31063103	3	70	with	patients	474:481	arg1	algorithm					499:507	Geno2pheno algorithm	488:507	Geno2pheno algorithm at a false-positive rate of 10%	488:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	7	71	theme	Sequences	1030:1038	arg1	analysis					1040:1047	Sequences analysis	1030:1047	Sequences analysis of V3	1030:1053	Sequences analysis of V3 revealed a higher median net charge in the CXCR4 viruses over CCR5 viruses (4.0 vs. 3.0, P &lt; 0.05).
31063103	1	72	from	transmission	191:202	arg1	patients					235:242	patients	235:242	patients	235:242	Co-receptor tropism has been identified to correlate with HIV-1 transmission and the disease progression in patients.
31063103	3	73	theme	false-positive	514:527	arg1	rate					529:532	a false-positive rate	512:532	a false-positive rate of 10%	512:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	8	74	theme	N-linked	1172:1179	arg1	site					1195:1198	The predicted N-linked glycosylation site	1158:1198	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region	1158:1243	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31063103	9	75	theme	prevalent	1397:1405	arg1	GPGQ					1413:1416	the most prevalent motif GPGQ	1388:1416	the most prevalent motif GPGQ	1388:1416	Besides, variable crown motifs were observed in both CCR5 and CXCR4 viruses, of which the most prevalent motif GPGQ existed in both viral tropism and almost all genotypes identified in this study except subtype B.
31063103	3	76	theme	patients	474:481	arg1	variants					438:445	HIV-1 variants	432:445	HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%	432:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	0	77	theme	regions	58:64	arg1	tropism					12:18	Co-receptor tropism	0:18	Co-receptor tropism	0:18	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	0	77	theme	regions	58:64	arg1	characteristics					32:46	genetic characteristics	24:46	genetic characteristics	24:46	Co-receptor tropism and genetic characteristics of the V3 regions in variants of antiretroviral-naive HIV-1 infected subjects.
31063103	3	78	from	tropism	421:427	arg1	variants					438:445	HIV-1 variants	432:445	HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%	432:539	In this study, we investigated the co-receptor tropism on HIV-1 variants of 85 antiretroviral-naive patients with Geno2pheno algorithm at a false-positive rate of 10%.
31063103	2	79	theme	epidemiology	257:268	arg1	important					310:318	important	310:318	important	310:318	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	2	79	theme	epidemiology	257:268	arg1	investigation					270:282	A molecular epidemiology investigation	245:282	A molecular epidemiology investigation of co-receptor tropism	245:305	A molecular epidemiology investigation of co-receptor tropism is important for clinical practice and effective control of HIV-1.
31063103	8	80	theme	CCR5	1262:1265	arg1	viruses					1267:1273	CCR5 viruses	1262:1273	CCR5 viruses	1262:1273	The predicted N-linked glycosylation site between amino acids 6 and 8 in the V3 region was conserved in CCR5 viruses, but not in CXCR4 viruses.
31018136	7	0	theme	detailed	1113:1120	arg1	information					1122:1132	detailed information	1113:1132	detailed information on altered biosynthetic paths	1113:1162	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	1	1	theme	eukaryotic	176:185	arg1	life					187:190	eukaryotic life	176:190	eukaryotic life	176:190	The decoration of proteins by carbohydrates is essential for eukaryotic life yet heterogeneous due to a lack of biosynthetic templates.
31018136	0	2	theme	Cellular	89:96	arg1	Differentiation					98:112	Cellular Differentiation	89:112	Cellular Differentiation	89:112	Modeling Glycan Processing Reveals Golgi-Enzyme Homeostasis upon Trafficking Defects and Cellular Differentiation.
31018136	3	3	theme	different	552:560	arg1	profiles					569:576	different glycan profiles	552:576	different glycan profiles	552:576	Here, we develop and validate a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles.
31018136	5	4	theme	modeling	795:802	arg1	field					779:783	the field	775:783	the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states	775:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	5	5	from	machinery	864:872	arg1	states					894:899	altered cellular states	877:899	altered cellular states	877:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	2	6	theme	compartmentalized	324:340	arg1	Golgi					342:346	the compartmentalized Golgi	320:346	the compartmentalized Golgi	320:346	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	6	7	theme	intra-Golgi-enzyme	999:1016	arg1	sorting					1018:1024	perturbed intra-Golgi-enzyme sorting	989:1024	perturbed intra-Golgi-enzyme sorting	989:1024	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	2	8	theme	enzymes	398:404	arg1	localization					368:379	localization	368:379	localization	368:379	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	2	8	theme	enzymes	398:404	arg1	level					358:362	level	358:362	level	358:362	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	2	8	theme	enzymes	398:404	arg1	determinants					414:425	key determinants	410:425	key determinants	410:425	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	4	9	theme	rigorous	646:653	arg1	comparison					655:664	rigorous comparison	646:664	rigorous comparison to experimental data	646:685	We combined stochastic modeling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters.
31018136	3	10	theme	biosynthetic	521:532	arg1	machinery					534:542	the biosynthetic machinery	517:542	the biosynthetic machinery	517:542	Here, we develop and validate a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles.
31018136	5	11	theme	cellular	885:892	arg1	states					894:899	altered cellular states	877:899	altered cellular states	877:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	6	12	from	changes	930:936	arg1	enzymes					967:973	N-linked glycan-modifying enzymes	941:973	N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis	941:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	7	13	theme	cells	1265:1269	arg1	glyco-engineering					1244:1260	glyco-engineering	1244:1260	glyco-engineering of cells	1244:1269	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	7	13	theme	cells	1265:1269	arg1	diseases					1231:1238	glycosylation-related diseases	1209:1238	glycosylation-related diseases	1209:1238	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	0	14	theme	Glycan	9:14	arg1	Processing					16:25	Modeling Glycan Processing	0:25	Modeling Glycan Processing	0:25	Modeling Glycan Processing Reveals Golgi-Enzyme Homeostasis upon Trafficking Defects and Cellular Differentiation.
31018136	7	15	theme	advancing	1184:1192	arg1	treatments					1194:1203	advancing treatments	1184:1203	advancing treatments for glycosylation-related diseases and glyco-engineering of cells	1184:1269	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	6	16	theme	perturbed	989:997	arg1	sorting					1018:1024	perturbed intra-Golgi-enzyme sorting	989:1024	perturbed intra-Golgi-enzyme sorting	989:1024	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	7	17	from	information	1122:1132	arg1	paths					1158:1162	altered biosynthetic paths	1137:1162	altered biosynthetic paths	1137:1162	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	0	18	theme	Modeling	0:7	arg1	Processing					16:25	Modeling Glycan Processing	0:25	Modeling Glycan Processing	0:25	Modeling Glycan Processing Reveals Golgi-Enzyme Homeostasis upon Trafficking Defects and Cellular Differentiation.
31018136	3	19	theme	computational	460:472	arg1	model					474:478	a computational model	458:478	a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles	458:576	Here, we develop and validate a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles.
31018136	7	20	theme	glycosylation-related	1209:1229	arg1	diseases					1231:1238	glycosylation-related diseases	1209:1238	glycosylation-related diseases	1209:1238	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	6	21	from	enzymes	967:973	arg1	cells					978:982	cells	978:982	cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis	978:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	2	22	theme	glycosylation	384:396	arg1	enzymes					398:404	glycosylation enzymes	384:404	glycosylation enzymes	384:404	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	3	23	theme	glycan	562:567	arg1	profiles					569:576	different glycan profiles	552:576	different glycan profiles	552:576	Here, we develop and validate a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles.
31018136	5	24	theme	glycosylation	850:862	arg1	machinery					864:872	the glycosylation machinery	846:872	the glycosylation machinery in altered cellular states	846:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	4	25	theme	Bayesian	616:623	arg1	fitting					625:631	Bayesian fitting	616:631	Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters	616:736	We combined stochastic modeling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters.
31018136	4	26	theme	initial	719:725	arg1	parameters					727:736	uncertain initial parameters	709:736	uncertain initial parameters	709:736	We combined stochastic modeling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters.
31018136	2	27	theme	complex	256:262	arg1	profile-is					296:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	3	28	theme	glycan	484:489	arg1	biosynthesis					491:502	glycan biosynthesis	484:502	glycan biosynthesis	484:502	Here, we develop and validate a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles.
31018136	0	29	theme	Golgi-Enzyme	35:46	arg1	Homeostasis					48:58	Golgi-Enzyme Homeostasis	35:58	Golgi-Enzyme Homeostasis	35:58	Modeling Glycan Processing Reveals Golgi-Enzyme Homeostasis upon Trafficking Defects and Cellular Differentiation.
31018136	5	30	theme	glycan	788:793	arg1	modeling					795:802	glycan modeling	788:802	glycan modeling	788:802	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	6	31	theme	glycan-modifying	950:965	arg1	enzymes					967:973	N-linked glycan-modifying enzymes	941:973	N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis	941:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	1	32	theme	biosynthetic	227:238	arg1	templates					240:248	biosynthetic templates	227:248	biosynthetic templates	227:248	The decoration of proteins by carbohydrates is essential for eukaryotic life yet heterogeneous due to a lack of biosynthetic templates.
31018136	0	33	theme	Trafficking	65:75	arg1	Defects					77:83	Trafficking Defects	65:83	Trafficking Defects	65:83	Modeling Glycan Processing Reveals Golgi-Enzyme Homeostasis upon Trafficking Defects and Cellular Differentiation.
31018136	6	34	theme	N-linked	941:948	arg1	enzymes					967:973	N-linked glycan-modifying enzymes	941:973	N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis	941:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	2	35	from	determinants	414:425	arg1	Golgi					342:346	the compartmentalized Golgi	320:346	the compartmentalized Golgi	320:346	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	1	36	theme	proteins	133:140	arg1	decoration					119:128	The decoration	115:128	The decoration of proteins by carbohydrates	115:157	The decoration of proteins by carbohydrates is essential for eukaryotic life yet heterogeneous due to a lack of biosynthetic templates.
31018136	1	36	theme	proteins	133:140	arg1	essential					162:170	essential	162:170	essential	162:170	The decoration of proteins by carbohydrates is essential for eukaryotic life yet heterogeneous due to a lack of biosynthetic templates.
31018136	5	37	theme	altered	877:883	arg1	states					894:899	altered cellular states	877:899	altered cellular states	877:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	4	38	theme	stochastic	591:600	arg1	modeling					602:609	stochastic modeling	591:609	stochastic modeling	591:609	We combined stochastic modeling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters.
31018136	5	39	theme	important	750:758	arg1	development					760:770	an important development	747:770	an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states	747:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	5	39	theme	important	750:758	arg1	This					739:742	This	739:742	This	739:742	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	7	40	theme	altered	1137:1143	arg1	paths					1158:1162	altered biosynthetic paths	1137:1162	altered biosynthetic paths	1137:1162	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	6	41	link	N-linked	941:948	arg1	enzymes					967:973	N-linked glycan-modifying enzymes	941:973	N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis	941:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	6	42	theme	glycan-branching	1044:1059	arg1	activity					1061:1068	the predicted glycan-branching activity	1030:1068	the predicted glycan-branching activity during osteogenesis	1030:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	7	43	theme	biosynthetic	1145:1156	arg1	paths					1158:1162	altered biosynthetic paths	1137:1162	altered biosynthetic paths	1137:1162	Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
31018136	5	44	from	development	760:770	arg1	field					779:783	the field	775:783	the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states	775:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	1	45	theme	templates	240:248	arg1	lack					219:222	a lack	217:222	a lack of biosynthetic templates	217:248	The decoration of proteins by carbohydrates is essential for eukaryotic life yet heterogeneous due to a lack of biosynthetic templates.
31018136	2	46	theme	glycan	289:294	arg1	profile-is					296:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	6	47	with	cells	978:982	arg1	activity					1061:1068	the predicted glycan-branching activity	1030:1068	the predicted glycan-branching activity during osteogenesis	1030:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	6	47	with	cells	978:982	arg1	sorting					1018:1024	perturbed intra-Golgi-enzyme sorting	989:1024	perturbed intra-Golgi-enzyme sorting	989:1024	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	5	48	theme	biological	820:829	arg1	insights					831:838	biological insights	820:838	biological insights about the glycosylation machinery in altered cellular states	820:899	This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states.
31018136	4	49	theme	uncertain	709:717	arg1	parameters					727:736	uncertain initial parameters	709:736	uncertain initial parameters	709:736	We combined stochastic modeling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters.
31018136	2	50	theme	mixture-the	277:287	arg1	profile-is					296:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	2	51	theme	key	410:412	arg1	localization					368:379	localization	368:379	localization	368:379	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	2	51	theme	key	410:412	arg1	determinants					414:425	key determinants	410:425	key determinants	410:425	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	2	51	theme	key	410:412	arg1	level					358:362	level	358:362	level	358:362	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	6	52	theme	predicted	1034:1042	arg1	activity					1061:1068	the predicted glycan-branching activity	1030:1068	the predicted glycan-branching activity during osteogenesis	1030:1088	We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis.
31018136	2	53	theme	carbohydrate	264:275	arg1	profile-is					296:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is	251:305	This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants.
31018136	4	54	theme	experimental	669:680	arg1	data					682:685	experimental data	669:685	experimental data	669:685	We combined stochastic modeling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters.
30901908	1	0	theme	disulphide	333:342	arg1	bonds					344:348	disulphide bonds	333:348	disulphide bonds	333:348	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	2	1	theme	precursor	614:622	arg1	pools					624:628	glycan precursor pools	607:628	glycan precursor pools	607:628	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	1	2	theme	Escherichia	154:164	arg1	strains					171:177	Escherichia coli strains	154:177	Escherichia coli strains	154:177	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	1	3	link	N-linked	393:400	arg1	glycosylation					402:414	N-linked glycosylation	393:414	N-linked glycosylation	393:414	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	3	4	theme	enhanced	833:840	arg1	uptake					842:847	the enhanced uptake	829:847	the enhanced uptake	829:847	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	2	5	theme	central	552:558	arg1	pathways					577:584	central carbon metabolic pathways	552:584	central carbon metabolic pathways	552:584	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	0	6	from	Pathways	12:19	arg1	Metabolism					39:48	Central Carbon Metabolism	24:48	Central Carbon Metabolism	24:48	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	2	7	theme	glycan	607:612	arg1	pools					624:628	glycan precursor pools	607:628	glycan precursor pools	607:628	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	4	8	theme	positive	1226:1233	arg1	impact					1235:1240	a positive impact	1224:1240	a positive impact	1224:1240	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	0	9	theme	N-Type	97:102	arg1	Glycosylation					104:116	N-Type Glycosylation	97:116	N-Type Glycosylation of Recombinant Proteins in E. coli	97:151	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	1	10	with	proteins	319:326	arg1	bonds					344:348	disulphide bonds	333:348	disulphide bonds	333:348	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	1	11	theme	different	248:256	arg1	proteins					270:277	different recombinant proteins	248:277	different recombinant proteins	248:277	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	4	12	theme	gene	1130:1133	arg1	overexpression					1110:1123	overexpression	1110:1123	overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation,	1110:1258	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	1	13	theme	recombinant	258:268	arg1	proteins					270:277	different recombinant proteins	248:277	different recombinant proteins	248:277	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	3	14	theme	glycans	743:749	arg1	representation					725:738	cell surface representation	712:738	cell surface representation of glycans	712:749	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	15	theme	engineered	1062:1071	arg1	IFN-α2b					1087:1093	an engineered human protein IFN-α2b	1059:1093	an engineered human protein IFN-α2b	1059:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	16	theme	surface	717:723	arg1	representation					725:738	cell surface representation	712:738	cell surface representation of glycans	712:749	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	2	17	theme	prior	631:635	arg1	pools					624:628	glycan precursor pools	607:628	glycan precursor pools	607:628	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	4	18	contain	have	1219:1222	arg1	dxs					1184:1186	dxs	1184:1186	dxs	1184:1186	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	4	18	contain	have	1219:1222	arg2	impact					1235:1240	a positive impact	1224:1240	a positive impact	1224:1240	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	4	18	contain	have	1219:1222	arg1	pyruvate					1174:1181	pyruvate	1174:1181	pyruvate (dxs)	1174:1187	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	4	19	dep	this	1327:1330	arg1	discussed					1336:1344	discussed	1336:1344	are discussed	1332:1344	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	3	20	from	%	1054:1054	arg1	IFN-α2b					1087:1093	an engineered human protein IFN-α2b	1059:1093	an engineered human protein IFN-α2b	1059:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	1	21	dep	Escherichia	154:164	arg1	coli					166:169	coli	166:169	coli	166:169	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	0	22	theme	Engineering	0:10	arg1	Pathways					12:19	Engineering Pathways	0:19	Engineering Pathways in Central Carbon Metabolism	0:48	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	1	23	theme	proteins	270:277	arg1	production					234:243	the production	230:243	the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation	230:414	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	1	24	with	proteins	270:277	arg1	bonds					344:348	disulphide bonds	333:348	disulphide bonds	333:348	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	4	25	theme	possible	1306:1313	arg1	reasons					1315:1321	the possible reasons	1302:1321	the possible reasons for this are discussed	1302:1344	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	3	26	theme	carbon	931:936	arg1	conservation					915:926	conservation	915:926	conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b	915:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	0	27	theme	Central	24:30	arg1	Metabolism					39:48	Central Carbon Metabolism	24:48	Central Carbon Metabolism	24:48	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	3	28	theme	Western	766:772	arg1	analyses					779:786	Western blot analyses	766:786	Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b	766:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	0	29	theme	Proteins	133:140	arg1	Glycosylation					104:116	N-Type Glycosylation	97:116	N-Type Glycosylation of Recombinant Proteins in E. coli	97:151	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	3	30	theme	AcrA	1030:1033	arg1	efficiency					996:1005	the glyoxylate shunt (icl) improved glycosylation efficiency	946:1005	the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69%	946:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	0	31	gly	Glycosylation	104:116	arg1	Proteins					133:140	Recombinant Proteins	121:140	Recombinant Proteins	121:140	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	1	32	theme	targeting	280:288	arg1	production					234:243	the production	230:243	the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation	230:414	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	0	33	theme	Recombinant	121:131	arg1	Proteins					133:140	Recombinant Proteins	121:140	Recombinant Proteins	121:140	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	1	34	theme	proteins	370:377	arg1	production					234:243	the production	230:243	the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation	230:414	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	1	35	with	proteins	370:377	arg1	bonds					344:348	disulphide bonds	333:348	disulphide bonds	333:348	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	2	36	theme	inefficient	474:484	arg1	process					486:492	a relatively inefficient process	461:492	a relatively inefficient process	461:492	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	1	37	theme	membrane	290:297	arg1	expression					307:316	membrane protein expression	290:316	membrane protein expression	290:316	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	3	38	theme	human	1073:1077	arg1	IFN-α2b					1087:1093	an engineered human protein IFN-α2b	1059:1093	an engineered human protein IFN-α2b	1059:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	39	theme	sugars	872:877	arg1	strain					821:826	an O-antigen ligase mutant strain	794:826	an O-antigen ligase mutant strain	794:826	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	39	theme	sugars	872:877	arg1	phosphorylation					853:867	phosphorylation	853:867	phosphorylation of sugars (ptsA)	853:884	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	39	theme	sugars	872:877	arg1	uptake					842:847	the enhanced uptake	829:847	the enhanced uptake	829:847	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	0	40	theme	Carbon	32:37	arg1	Metabolism					39:48	Central Carbon Metabolism	24:48	Central Carbon Metabolism	24:48	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	1	41	theme	protein	299:305	arg1	expression					307:316	membrane protein expression	290:316	membrane protein expression	290:316	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	3	42	theme	protein	1079:1085	arg1	IFN-α2b					1087:1093	an engineered human protein IFN-α2b	1059:1093	an engineered human protein IFN-α2b	1059:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	2	43	theme	glycans	433:439	arg1	addition					421:428	The addition	417:428	The addition of glycans to proteins	417:451	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	3	44	theme	shunt	961:965	arg1	efficiency					996:1005	the glyoxylate shunt (icl) improved glycosylation efficiency	946:1005	the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69%	946:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	2	45	theme	genetic	523:529	arg1	modifications					531:543	genetic modifications	523:543	genetic modifications within central carbon metabolic pathways	523:584	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	1	46	theme	N-linked	393:400	arg1	glycosylation					402:414	N-linked glycosylation	393:414	N-linked glycosylation	393:414	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	4	47	from	pyruvate	1174:1181	arg1	production					1151:1160	the production	1147:1160	the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation,	1147:1258	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	3	48	theme	blot	774:777	arg1	analyses					779:786	Western blot analyses	766:786	Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b	766:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	2	49	theme	carbon	560:565	arg1	pathways					577:584	central carbon metabolic pathways	552:584	central carbon metabolic pathways	552:584	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	3	50	theme	lectin	685:690	arg1	screen					692:697	a lectin screen	683:697	a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b	683:1093	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	4	51	theme	DXP	1165:1167	arg1	production					1151:1160	the production	1147:1160	the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation,	1147:1258	Unexpectedly, overexpression of a gene involved in the production of DXP from pyruvate (dxs), which was previously seen to have a positive impact on glycosylation, was detrimental to process efficiency and the possible reasons for this are discussed.
30901908	1	52	theme	proteins	319:326	arg1	production					234:243	the production	230:243	the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation	230:414	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	0	53	from	Glycosylation	104:116	arg1	coli					148:151	E. coli	145:151	E. coli	145:151	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	2	54	theme	polypeptide	654:664	arg1	backbones					666:674	polypeptide backbones	654:674	polypeptide backbones	654:674	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	3	55	theme	icl	968:970	arg1	efficiency					996:1005	the glyoxylate shunt (icl) improved glycosylation efficiency	946:1005	the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69%	946:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	1	56	theme	ways	214:217	arg1	ways					214:217	ways	214:217	ways	214:217	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	1	56	theme	ways	214:217	arg1	variety					203:209	a variety	201:209	a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation	201:414	Escherichia coli strains have been modified in a variety of ways to enhance the production of different recombinant proteins, targeting membrane protein expression, proteins with disulphide bonds, and more recently, proteins which require N-linked glycosylation.
30901908	2	57	theme	metabolic	567:575	arg1	pathways					577:584	central carbon metabolic pathways	552:584	central carbon metabolic pathways	552:584	The addition of glycans to proteins remains a relatively inefficient process and here we aimed to combine genetic modifications within central carbon metabolic pathways in order to increase glycan precursor pools, prior to transfer onto polypeptide backbones.
30901908	3	58	theme	glyoxylate	950:959	arg1	efficiency					996:1005	the glyoxylate shunt (icl) improved glycosylation efficiency	946:1005	the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69%	946:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	59	theme	improved	973:980	arg1	efficiency					996:1005	the glyoxylate shunt (icl) improved glycosylation efficiency	946:1005	the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69%	946:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	0	60	theme	Glycan	67:72	arg1	Production					74:83	Glycan Production	67:83	Glycan Production	67:83	Engineering Pathways in Central Carbon Metabolism Help to Increase Glycan Production and Improve N-Type Glycosylation of Recombinant Proteins in E. coli.
30901908	3	61	theme	bacterial	1012:1020	arg1	AcrA					1030:1033	a bacterial protein AcrA	1010:1033	a bacterial protein AcrA by 69%	1010:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	62	theme	glycosylation	982:994	arg1	efficiency					996:1005	the glyoxylate shunt (icl) improved glycosylation efficiency	946:1005	the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69%	946:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	63	theme	protein	1022:1028	arg1	AcrA					1030:1033	a bacterial protein AcrA	1010:1033	a bacterial protein AcrA by 69%	1010:1040	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	64	theme	O-antigen	797:805	arg1	strain					821:826	an O-antigen ligase mutant strain	794:826	an O-antigen ligase mutant strain	794:826	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	65	theme	cell	712:715	arg1	representation					725:738	cell surface representation	712:738	cell surface representation of glycans	712:749	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	66	theme	mutant	814:819	arg1	strain					821:826	an O-antigen ligase mutant strain	794:826	an O-antigen ligase mutant strain	794:826	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30901908	3	67	theme	ligase	807:812	arg1	strain					821:826	an O-antigen ligase mutant strain	794:826	an O-antigen ligase mutant strain	794:826	Using a lectin screen that detects cell surface representation of glycans, together with Western blot analyses using an O-antigen ligase mutant strain, the enhanced uptake and phosphorylation of sugars (ptsA) from the media combined with conservation of carbon through the glyoxylate shunt (icl) improved glycosylation efficiency of a bacterial protein AcrA by 69% and over 100% in an engineered human protein IFN-α2b.
30881698	11	0	theme	Chip	1614:1617	arg1	MS					1625:1626	nano-LC Chip Q-ToF MS	1606:1626	nano-LC Chip Q-ToF MS	1606:1626	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	11	1	theme	immobilized	1450:1460	arg1	enzyme					1462:1467	The immobilized enzyme	1446:1467	The immobilized enzyme	1446:1467	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	9	2	theme	original	1266:1273	arg1	activity					1275:1282	its original activity	1262:1282	its original activity	1262:1282	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	10	3	theme	future	1328:1333	arg1	applications					1335:1346	future applications	1328:1346	future applications in the dairy industry	1328:1368	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	11	4	gly	sialylated	1572:1581	arg1	glycans					1583:1589	more sialylated glycans	1567:1589	more sialylated glycans	1567:1589	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	9	5	theme	immobilized	1222:1232	arg1	enzyme					1234:1239	the immobilized enzyme	1218:1239	the immobilized enzyme	1218:1239	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	5	6	theme	Amino-based	735:745	arg1	method					756:761	Amino-based covalent method	735:761	Amino-based covalent method	735:761	Amino-based covalent method showed the highest enzyme immobilization.
30881698	9	7	theme	activity	1275:1282	arg1	activity					1275:1282	its original activity	1262:1282	its original activity	1262:1282	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	9	7	theme	activity	1275:1282	arg1	%					1257:1257	50%	1255:1257	50% of its original activity	1255:1282	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	1	8	link	N-linked	201:208	arg1	glycans					210:216	N-linked glycans	201:216	N-linked glycans	201:216	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	10	9	theme	applications	1335:1346	arg1	view					1320:1323	view	1320:1323	view of future applications in the dairy industry	1320:1368	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	4	10	theme	model	650:654	arg1	B					634:634	Ribonuclease B	621:634	Ribonuclease B	621:634	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	4	10	theme	model	650:654	arg1	glycoprotein					656:667	a model glycoprotein	648:667	a model glycoprotein	648:667	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	6	11	theme	desorption/ionization	901:921	arg1	spectrometry					943:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	5	12	theme	covalent	747:754	arg1	method					756:761	Amino-based covalent method	735:761	Amino-based covalent method	735:761	Amino-based covalent method showed the highest enzyme immobilization.
30881698	3	13	theme	commensal	585:593	arg1	infantis					611:618	the commensal Bifidobacterium infantis	581:618	the commensal Bifidobacterium infantis	581:618	To increase throughput and enzyme reusability, this work evaluated several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis.
30881698	10	14	theme	whey	1431:1434	arg1	proteins					1436:1443	whey proteins	1431:1443	whey proteins	1431:1443	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	10	15	gly	deglycosylate	1417:1429	arg1	proteins					1436:1443	whey proteins	1431:1443	whey proteins	1431:1443	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	4	16	used	used	640:643	arg2	B					634:634	Ribonuclease B	621:634	Ribonuclease B	621:634	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	4	16	used	used	640:643	arg2	glycoprotein					656:667	a model glycoprotein	648:667	a model glycoprotein	648:667	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	11	17	theme	nano-LC	1606:1612	arg1	MS					1625:1626	nano-LC Chip Q-ToF MS	1606:1626	nano-LC Chip Q-ToF MS	1606:1626	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	11	18	theme	whey	1521:1524	arg1	proteins					1526:1533	whey proteins	1521:1533	whey proteins	1521:1533	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	10	19	theme	dairy	1355:1359	arg1	industry					1361:1368	the dairy industry	1351:1368	the dairy industry	1351:1368	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	11	20	theme	higher	1480:1485	arg1	abundance					1487:1495	a higher abundance	1478:1495	a higher abundance of neutral glycans	1478:1514	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	4	21	theme	free	706:709	arg1	enzyme					727:732	the free and immobilized enzyme	702:732	the free and immobilized enzyme	702:732	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	2	22	theme	selective	285:293	arg1	release					295:301	the selective release	281:301	the selective release of N-glycans	281:314	Protein deglycosylation allows for the selective release of N-glycans and facilitates glycoproteomic investigation into their roles as prebiotics or anti-pathogenic factors.
30881698	6	23	theme	Relative	805:812	arg1	abundance					814:822	Relative abundance	805:822	Relative abundance of N-glycans and enzyme activity	805:855	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	10	24	theme	enzyme	1407:1412	arg1	ability					1391:1397	the ability	1387:1397	the ability of this enzyme to deglycosylate whey proteins	1387:1443	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	1	25	from	roles	132:136	arg1	health					147:152	human health	141:152	human health	141:152	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	1	25	from	roles	132:136	arg1	disease					158:164	disease	158:164	disease	158:164	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	10	26	from	view	1320:1323	arg1	industry					1361:1368	the dairy industry	1351:1368	the dairy industry	1351:1368	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	9	27	theme	rapid	1196:1200	arg1	release					1209:1215	rapid glycan release	1196:1215	rapid glycan release	1196:1215	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	4	28	gly	glycoprotein	656:667	arg1	B					634:634	Ribonuclease B	621:634	Ribonuclease B	621:634	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	4	28	gly	glycoprotein	656:667	arg1	glycoprotein					656:667	a model glycoprotein	648:667	a model glycoprotein	648:667	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	2	29	theme	glycoproteomic	332:345	arg1	investigation					347:359	glycoproteomic investigation	332:359	glycoproteomic investigation into their roles as prebiotics or anti-pathogenic factors	332:417	Protein deglycosylation allows for the selective release of N-glycans and facilitates glycoproteomic investigation into their roles as prebiotics or anti-pathogenic factors.
30881698	9	30	theme	glycan	1202:1207	arg1	release					1209:1215	rapid glycan release	1196:1215	rapid glycan release	1196:1215	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	1	31	theme	biological	171:180	arg1	functionalities					182:196	the biological functionalities	167:196	the biological functionalities of N-linked glycans	167:216	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	6	32	theme	laser	895:899	arg1	spectrometry					943:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	8	33	theme	Optimal	1047:1053	arg1	values					1058:1063	Optimal pH values	1047:1063	Optimal pH values of 5 and 7	1047:1074	Optimal pH values of 5 and 7 were identified for the free and immobilized enzyme, respectively.
30881698	0	34	theme	Endo-β-N-acetylglucosaminidase	21:50	arg1	Immobilization					0:13	Immobilization	0:13	Immobilization of an Endo-β-N-acetylglucosaminidase for the Release of Bioactive N-glycans.	0:90	Immobilization of an Endo-β-N-acetylglucosaminidase for the Release of Bioactive N-glycans.
30881698	7	35	theme	Kinetic	957:963	arg1	evaluation					965:974	Kinetic evaluation	957:974	Kinetic evaluation	957:974	Kinetic evaluation demonstrated that upon immobilization, both Vmax and the Km decreased.
30881698	6	36	theme	mass	938:941	arg1	spectrometry					943:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	11	37	theme	Q-ToF	1619:1623	arg1	MS					1625:1626	nano-LC Chip Q-ToF MS	1606:1626	nano-LC Chip Q-ToF MS	1606:1626	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	1	38	gly	glycoproteins	117:129	arg1	glycoproteins					117:129	glycoproteins' roles	117:136	glycoproteins' roles in human health and disease	117:164	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	2	39	theme	N-glycans	306:314	arg1	release					295:301	the selective release	281:301	the selective release of N-glycans	281:314	Protein deglycosylation allows for the selective release of N-glycans and facilitates glycoproteomic investigation into their roles as prebiotics or anti-pathogenic factors.
30881698	1	40	theme	N-linked	201:208	arg1	glycans					210:216	N-linked glycans	201:216	N-linked glycans	201:216	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	3	41	theme	enzyme	447:452	arg1	reusability					454:464	enzyme reusability	447:464	enzyme reusability	447:464	To increase throughput and enzyme reusability, this work evaluated several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis.
30881698	11	42	dep	released	1469:1476	arg1	while					1536:1540	while	1536:1540	while	1536:1540	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	3	43	theme	several	487:493	arg1	methods					510:516	several immobilization methods	487:516	several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis	487:618	To increase throughput and enzyme reusability, this work evaluated several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis.
30881698	10	44	from	industry	1361:1368	arg1	view					1320:1323	view	1320:1323	view of future applications in the dairy industry	1320:1368	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	8	45	theme	pH	1055:1056	arg1	values					1058:1063	Optimal pH values	1047:1063	Optimal pH values of 5 and 7	1047:1074	Optimal pH values of 5 and 7 were identified for the free and immobilized enzyme, respectively.
30881698	1	46	theme	glycans	210:216	arg1	functionalities					182:196	the biological functionalities	167:196	the biological functionalities of N-linked glycans	167:216	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	10	47	from	applications	1335:1346	arg1	industry					1361:1368	the dairy industry	1351:1368	the dairy industry	1351:1368	In view of future applications in the dairy industry, we investigated the ability of this enzyme to deglycosylate whey proteins.
30881698	8	48	theme	5	1068:1068	arg1	values					1058:1063	Optimal pH values	1047:1063	Optimal pH values of 5 and 7	1047:1074	Optimal pH values of 5 and 7 were identified for the free and immobilized enzyme, respectively.
30881698	3	49	theme	immobilization	495:508	arg1	methods					510:516	several immobilization methods	487:516	several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis	487:618	To increase throughput and enzyme reusability, this work evaluated several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis.
30881698	8	50	theme	free	1100:1103	arg1	enzyme					1121:1126	the free and immobilized enzyme	1096:1126	the free and immobilized enzyme	1096:1126	Optimal pH values of 5 and 7 were identified for the free and immobilized enzyme, respectively.
30881698	11	51	theme	sialylated	1572:1581	arg1	glycans					1583:1589	more sialylated glycans	1567:1589	more sialylated glycans	1567:1589	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	6	52	theme	matrix-assisted	879:893	arg1	spectrometry					943:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	8	53	theme	7	1074:1074	arg1	values					1058:1063	Optimal pH values	1047:1063	Optimal pH values of 5 and 7	1047:1074	Optimal pH values of 5 and 7 were identified for the free and immobilized enzyme, respectively.
30881698	4	54	theme	Ribonuclease	621:632	arg1	B					634:634	Ribonuclease B	621:634	Ribonuclease B	621:634	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	4	54	theme	Ribonuclease	621:632	arg1	glycoprotein					656:667	a model glycoprotein	648:667	a model glycoprotein	648:667	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	5	55	theme	highest	774:780	arg1	immobilization					789:802	the highest enzyme immobilization	770:802	the highest enzyme immobilization	770:802	Amino-based covalent method showed the highest enzyme immobilization.
30881698	1	56	theme	human	141:145	arg1	health					147:152	human health	141:152	human health	141:152	As more is learned about glycoproteins' roles in human health and disease, the biological functionalities of N-linked glycans are becoming more relevant.
30881698	6	57	theme	activity	848:855	arg1	abundance					814:822	Relative abundance	805:822	Relative abundance of N-glycans and enzyme activity	805:855	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	6	58	theme	time-of-flight	923:936	arg1	spectrometry					943:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	879:954	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	9	59	theme	higher	1154:1159	arg1	temperature					1161:1171	a higher temperature	1152:1171	a higher temperature (65 vs. 45 °C)	1152:1186	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	9	59	theme	higher	1154:1159	arg1	°C					1184:1185	65 vs. 45 °C	1174:1185	65 vs. 45 °C	1174:1185	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	5	60	theme	enzyme	782:787	arg1	immobilization					789:802	the highest enzyme immobilization	770:802	the highest enzyme immobilization	770:802	Amino-based covalent method showed the highest enzyme immobilization.
30881698	6	61	theme	enzyme	841:846	arg1	activity					848:855	enzyme activity	841:855	enzyme activity	841:855	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	11	62	theme	free	1546:1549	arg1	enzyme					1551:1556	the free enzyme	1542:1556	the free enzyme	1542:1556	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	9	63	theme	use	1296:1298	arg1	cycles					1300:1305	seven use cycles	1290:1305	seven use cycles	1290:1305	Although a higher temperature (65 vs. 45 °C) favored rapid glycan release, the immobilized enzyme retained over 50% of its original activity after seven use cycles at 45 °C.
30881698	11	64	theme	glycans	1508:1514	arg1	abundance					1487:1495	a higher abundance	1478:1495	a higher abundance of neutral glycans	1478:1514	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30881698	0	65	theme	N-glycans	81:89	arg1	Release					60:66	the Release	56:66	the Release of Bioactive N-glycans	56:89	Immobilization of an Endo-β-N-acetylglucosaminidase for the Release of Bioactive N-glycans.
30881698	4	66	theme	immobilized	715:725	arg1	enzyme					727:732	the free and immobilized enzyme	702:732	the free and immobilized enzyme	702:732	Ribonuclease B was used as a model glycoprotein to compare N-glycans released by the free and immobilized enzyme.
30881698	2	67	theme	anti-pathogenic	395:409	arg1	factors					411:417	anti-pathogenic factors	395:417	anti-pathogenic factors	395:417	Protein deglycosylation allows for the selective release of N-glycans and facilitates glycoproteomic investigation into their roles as prebiotics or anti-pathogenic factors.
30881698	8	68	theme	immobilized	1109:1119	arg1	enzyme					1121:1126	the free and immobilized enzyme	1096:1126	the free and immobilized enzyme	1096:1126	Optimal pH values of 5 and 7 were identified for the free and immobilized enzyme, respectively.
30881698	0	69	theme	Bioactive	71:79	arg1	N-glycans					81:89	Bioactive N-glycans	71:89	Bioactive N-glycans	71:89	Immobilization of an Endo-β-N-acetylglucosaminidase for the Release of Bioactive N-glycans.
30881698	2	70	theme	Protein	246:252	arg1	deglycosylation					254:268	Protein deglycosylation	246:268	Protein deglycosylation	246:268	Protein deglycosylation allows for the selective release of N-glycans and facilitates glycoproteomic investigation into their roles as prebiotics or anti-pathogenic factors.
30881698	6	71	theme	N-glycans	827:835	arg1	abundance					814:822	Relative abundance	805:822	Relative abundance of N-glycans and enzyme activity	805:855	Relative abundance of N-glycans and enzyme activity were determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
30881698	3	72	theme	Bifidobacterium	595:609	arg1	infantis					611:618	the commensal Bifidobacterium infantis	581:618	the commensal Bifidobacterium infantis	581:618	To increase throughput and enzyme reusability, this work evaluated several immobilization methods for an endo-β-N-acetylglucosaminidase recently discovered from the commensal Bifidobacterium infantis.
30881698	11	73	theme	neutral	1500:1506	arg1	glycans					1508:1514	neutral glycans	1500:1514	neutral glycans	1500:1514	The immobilized enzyme released a higher abundance of neutral glycans from whey proteins, while the free enzyme released more sialylated glycans, determined by nano-LC Chip Q-ToF MS.
30072579	10	0	theme	Glycomic	1685:1692	arg1	data					1694:1697	Glycomic data	1685:1697	Glycomic data	1685:1697	Glycomic data are available via ProteomeXchange with identifier PXD010086.
30072579	2	1	theme	driver	334:339	arg1	mutations					341:349	other common driver mutations	321:349	other common driver mutations	321:349	KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent.
30072579	8	2	from	deletion	1511:1518	arg1	gene					1555:1558	the GDP-mannose 4,6-dehydratase gene	1523:1558	the GDP-mannose 4,6-dehydratase gene	1523:1558	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	4	3	theme	Glycan	501:506	arg1	profiles					508:515	Glycan profiles	501:515	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens	501:603	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	2	4	theme	common	327:332	arg1	mutations					341:349	other common driver mutations	321:349	other common driver mutations	321:349	KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent.
30072579	1	5	theme	mucinous	246:253	arg1	ascites					255:261	mucinous ascites	246:261	mucinous ascites	246:261	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	10	6	with	ProteomeXchange	1717:1731	arg1	identifier					1738:1747	identifier PXD010086	1738:1757	identifier PXD010086	1738:1757	Glycomic data are available via ProteomeXchange with identifier PXD010086.
30072579	7	7	theme	PMP	1139:1141	arg1	cells					1143:1147	PMP cells	1139:1147	PMP cells	1139:1147	Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry.
30072579	9	8	theme	characteristic	1645:1658	arg1	production					1666:1675	the characteristic mucin production	1641:1675	the characteristic mucin production of PMP	1641:1682	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	4	9	theme	high-grade	580:589	arg1	specimens					595:603	eight low-grade and eight high-grade PMP specimens	554:603	specimens	595:603	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	9	10	attach	linked	1631:1636	arg2	glycosylation					1575:1587	altered glycosylation	1567:1587	altered glycosylation especially in the form of fucosylation	1567:1626	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	9	10	attach	linked	1631:1636	arg1	production					1666:1675	the characteristic mucin production	1641:1675	the characteristic mucin production of PMP	1641:1682	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	9	11	theme	altered	1567:1573	arg1	glycosylation					1575:1587	altered glycosylation	1567:1587	altered glycosylation especially in the form of fucosylation	1567:1626	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	2	12	theme	GNAS	273:276	arg1	mutations					278:286	GNAS mutations	273:286	GNAS mutations	273:286	KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent.
30072579	9	13	from	glycosylation	1575:1587	arg1	form					1607:1610	the form	1603:1610	the form of fucosylation	1603:1626	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	3	14	theme	normal	484:489	arg1	appendix					491:498	normal appendix	484:498	normal appendix	484:498	As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix.
30072579	6	15	theme	PMP	1010:1012	arg1	tissues					1014:1020	PMP tissues	1010:1020	PMP tissues	1010:1020	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	8	16	theme	fucosylation	1214:1225	arg1	restoration					1199:1209	restoration	1199:1209	restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase	1199:1325	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	6	17	theme	enzymes	902:908	arg1	expression					862:871	up-regulated mRNA expression	844:871	up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues	844:1020	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	8	18	theme	GDP-mannose	1299:1309	arg1	4,6-dehydratase					1311:1325	intact GDP-mannose 4,6-dehydratase	1292:1325	intact GDP-mannose 4,6-dehydratase	1292:1325	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	9	19	theme	fucosylation	1615:1626	arg1	form					1607:1610	the form	1603:1610	the form of fucosylation	1603:1626	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	8	20	theme	mucin	1380:1384	arg1	molecule					1386:1393	the predominant mucin molecule	1364:1393	the predominant mucin molecule secreted by the PMP cells	1364:1419	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	8	20	theme	mucin	1380:1384	arg1	MUC2					1349:1352	MUC2	1349:1352	MUC2	1349:1352	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	5	21	theme	prominent	772:780	arg1	alteration					782:791	the most prominent alteration	763:791	the most prominent alteration	763:791	Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation.
30072579	6	22	theme	fucosylation-related	881:900	arg1	enzymes					902:908	four fucosylation-related enzymes	876:908	four fucosylation-related enzymes	876:908	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	6	22	theme	fucosylation-related	881:900	arg1	fucosylation					920:931	the core fucosylation	911:931	the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues	911:1020	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	0	23	theme	Glycomic	0:7	arg1	Profiling					9:17	Glycomic Profiling	0:17	Glycomic Profiling	0:17	Glycomic Profiling Highlights Increased Fucosylation in Pseudomyxoma Peritonei.
30072579	3	24	theme	N-linked	432:439	arg1	profiles					448:455	N-linked glycan profiles	432:455	N-linked glycan profiles of PMP tissues	432:470	As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix.
30072579	0	25	from	Fucosylation	40:51	arg1	Peritonei					69:77	Peritonei	69:77	Peritonei	69:77	Glycomic Profiling Highlights Increased Fucosylation in Pseudomyxoma Peritonei.
30072579	4	26	theme	samples	542:548	arg1	profiles					508:515	Glycan profiles	501:515	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens	501:603	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	9	27	gly	glycosylation	1575:1587	arg1	form					1607:1610	the form	1603:1610	the form of fucosylation	1603:1626	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	8	28	theme	intact	1292:1297	arg1	4,6-dehydratase					1311:1325	intact GDP-mannose 4,6-dehydratase	1292:1325	intact GDP-mannose 4,6-dehydratase	1292:1325	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	3	29	theme	altered	370:376	arg1	glycosylation					378:390	altered glycosylation	370:390	altered glycosylation	370:390	As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix.
30072579	2	30	located	found	303:307	arg2	KRAS					264:267	KRAS	264:267	KRAS	264:267	KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent.
30072579	2	30	located	found	303:307	arg1	PMP					312:314	PMP	312:314	PMP	312:314	KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent.
30072579	2	30	located	found	303:307	arg2	mutations					278:286	GNAS mutations	273:286	GNAS mutations	273:286	KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent.
30072579	3	31	link	N-linked	432:439	arg1	profiles					448:455	N-linked glycan profiles	432:455	N-linked glycan profiles of PMP tissues	432:470	As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix.
30072579	7	32	theme	latter	1094:1099	arg1	enzymes					1107:1113	the latter three enzymes	1090:1113	the latter three enzymes	1090:1113	Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry.
30072579	8	33	theme	GDP-mannose	1527:1537	arg1	gene					1555:1558	the GDP-mannose 4,6-dehydratase gene	1523:1558	the GDP-mannose 4,6-dehydratase gene	1523:1558	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	0	34	theme	Increased	30:38	arg1	Fucosylation					40:51	Increased Fucosylation	30:51	Increased Fucosylation in Pseudomyxoma Peritonei	30:77	Glycomic Profiling Highlights Increased Fucosylation in Pseudomyxoma Peritonei.
30072579	4	35	theme	appendix	533:540	arg1	samples					542:548	eight normal appendix samples	520:548	eight normal appendix samples	520:548	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	9	36	theme	PMP	1680:1682	arg1	production					1666:1675	the characteristic mucin production	1641:1675	the characteristic mucin production of PMP	1641:1682	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	9	37	theme	mucin	1660:1664	arg1	production					1666:1675	the characteristic mucin production	1641:1675	the characteristic mucin production of PMP	1641:1682	Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP.
30072579	4	38	theme	mass	622:625	arg1	spectrometry					627:638	mass spectrometry	622:638	mass spectrometry	622:638	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	8	39	theme	salvage	1237:1243	arg1	pathway					1245:1251	salvage pathway	1237:1251	salvage pathway	1237:1251	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	6	40	theme	biosynthetic	986:997	arg1	enzymes					999:1005	fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes	944:1005	enzymes	999:1005	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	7	41	theme	enzymes	1107:1113	arg1	expression					1076:1085	Up-regulated protein expression	1055:1085	Up-regulated protein expression of the latter three enzymes	1055:1113	Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry.
30072579	8	42	theme	predominant	1368:1378	arg1	molecule					1386:1393	the predominant mucin molecule	1364:1393	the predominant mucin molecule secreted by the PMP cells	1364:1419	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	8	42	theme	predominant	1368:1378	arg1	MUC2					1349:1352	MUC2	1349:1352	MUC2	1349:1352	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	3	43	theme	PMP	460:462	arg1	tissues					464:470	PMP tissues	460:470	PMP tissues	460:470	As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix.
30072579	6	44	theme	GDP-fucose	975:984	arg1	enzymes					999:1005	fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes	944:1005	enzymes	999:1005	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	1	45	theme	Pseudomyxoma	80:91	arg1	peritonei					93:101	Pseudomyxoma peritonei	80:101	Pseudomyxoma peritonei (PMP)	80:107	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	1	45	theme	Pseudomyxoma	80:91	arg1	subtype					114:120	a subtype	112:120	a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites	112:261	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	1	45	theme	Pseudomyxoma	80:91	arg1	PMP					104:106	PMP	104:106	PMP	104:106	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	8	46	theme	intestinal-derived	1428:1445	arg1	line					1467:1470	an intestinal-derived adenocarcinoma cell line	1425:1470	an intestinal-derived adenocarcinoma cell line with defective fucosylation	1425:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	3	47	theme	glycan	441:446	arg1	profiles					448:455	N-linked glycan profiles	432:455	N-linked glycan profiles of PMP tissues	432:470	As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix.
30072579	8	48	theme	expression	1278:1287	arg1	introduction					1259:1270	introduction	1259:1270	introduction of an expression of intact GDP-mannose 4,6-dehydratase	1259:1325	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	4	49	theme	low-grade	560:568	arg1	profiles					508:515	Glycan profiles	501:515	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens	501:603	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	6	50	theme	mRNA	857:860	arg1	expression					862:871	up-regulated mRNA expression	844:871	up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues	844:1020	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	8	51	gly	fucosylation	1487:1498	arg1	line					1467:1470	an intestinal-derived adenocarcinoma cell line	1425:1470	an intestinal-derived adenocarcinoma cell line with defective fucosylation	1425:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	8	52	theme	MUC2	1349:1352	arg1	expression					1335:1344	expression	1335:1344	expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation	1335:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	5	53	from	differences	658:668	arg1	profiles					680:687	glycan profiles	673:687	glycan profiles	673:687	Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation.
30072579	6	54	theme	up-regulated	844:855	arg1	expression					862:871	up-regulated mRNA expression	844:871	up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues	844:1020	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	8	55	theme	cell	1462:1465	arg1	line					1467:1470	an intestinal-derived adenocarcinoma cell line	1425:1470	an intestinal-derived adenocarcinoma cell line with defective fucosylation	1425:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	8	56	theme	PMP	1411:1413	arg1	cells					1415:1419	the PMP cells	1407:1419	the PMP cells	1407:1419	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	2	57	theme	other	321:325	arg1	mutations					341:349	other common driver mutations	321:349	other common driver mutations	321:349	KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent.
30072579	4	58	theme	PMP	591:593	arg1	specimens					595:603	eight low-grade and eight high-grade PMP specimens	554:603	specimens	595:603	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	4	59	theme	normal	526:531	arg1	samples					542:548	eight normal appendix samples	520:548	eight normal appendix samples	520:548	Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry.
30072579	5	60	theme	glycan	673:678	arg1	profiles					680:687	glycan profiles	673:687	glycan profiles	673:687	Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation.
30072579	6	61	theme	core	915:918	arg1	enzymes					902:908	four fucosylation-related enzymes	876:908	four fucosylation-related enzymes	876:908	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	6	61	theme	core	915:918	arg1	fucosylation					920:931	the core fucosylation	911:931	the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues	911:1020	We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls.
30072579	8	62	theme	adenocarcinoma	1447:1460	arg1	line					1467:1470	an intestinal-derived adenocarcinoma cell line	1425:1470	an intestinal-derived adenocarcinoma cell line with defective fucosylation	1425:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	8	63	with	line	1467:1470	arg1	fucosylation					1487:1498	defective fucosylation	1477:1498	defective fucosylation	1477:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	7	64	theme	Up-regulated	1055:1066	arg1	expression					1076:1085	Up-regulated protein expression	1055:1085	Up-regulated protein expression of the latter three enzymes	1055:1113	Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry.
30072579	1	65	theme	mucinous	125:132	arg1	adenocarcinoma					134:147	mucinous adenocarcinoma	125:147	mucinous adenocarcinoma	125:147	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	7	66	located	observed	1127:1134	arg1	cells					1143:1147	PMP cells	1139:1147	PMP cells	1139:1147	Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry.
30072579	7	66	located	observed	1127:1134	arg2	expression					1076:1085	Up-regulated protein expression	1055:1085	Up-regulated protein expression of the latter three enzymes	1055:1113	Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry.
30072579	1	67	theme	peritoneal	212:221	arg1	cavity					223:228	the peritoneal cavity	208:228	the peritoneal cavity filling it with mucinous ascites	208:261	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	7	68	theme	protein	1068:1074	arg1	expression					1076:1085	Up-regulated protein expression	1055:1085	Up-regulated protein expression of the latter three enzymes	1055:1113	Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry.
30072579	8	69	from	expression	1335:1344	arg1	line					1467:1470	an intestinal-derived adenocarcinoma cell line	1425:1470	an intestinal-derived adenocarcinoma cell line with defective fucosylation	1425:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	1	70	theme	adenocarcinoma	134:147	arg1	peritonei					93:101	Pseudomyxoma peritonei	80:101	Pseudomyxoma peritonei (PMP)	80:107	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	1	70	theme	adenocarcinoma	134:147	arg1	subtype					114:120	a subtype	112:120	a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites	112:261	Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites.
30072579	3	71	theme	tissues	464:470	arg1	profiles					448:455	N-linked glycan profiles	432:455	N-linked glycan profiles of PMP tissues	432:470	As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix.
30072579	8	72	theme	4,6-dehydratase	1539:1553	arg1	gene					1555:1558	the GDP-mannose 4,6-dehydratase gene	1523:1558	the GDP-mannose 4,6-dehydratase gene	1523:1558	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	8	73	theme	4,6-dehydratase	1311:1325	arg1	expression					1278:1287	an expression	1275:1287	an expression of intact GDP-mannose 4,6-dehydratase	1275:1325	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	8	74	link	intestinal-derived	1428:1445	arg1	line					1467:1470	an intestinal-derived adenocarcinoma cell line	1425:1470	an intestinal-derived adenocarcinoma cell line with defective fucosylation	1425:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
30072579	5	75	theme	neutral	742:748	arg1	glycans					750:756	neutral glycans	742:756	neutral glycans	742:756	Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation.
30072579	8	76	theme	defective	1477:1485	arg1	fucosylation					1487:1498	defective fucosylation	1477:1498	defective fucosylation	1477:1498	We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene.
29438977	7	0	theme	C	922:922	arg1	termini					924:930	novel in-frame C termini	907:930	novel in-frame C termini of 10 or 65 amino acids	907:954	variants with novel in-frame C termini of 10 or 65 amino acids.
29438977	6	1	dep	involves	824:831	arg1	alt					887:889	alt	887:889	alt	887:889	One abundant class of transcripts involves a novel exonic sequence and leads to two alternative (alt.)
29438977	5	2	theme	transcriptome	722:734	arg1	%					705:705	50%	703:705	50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas	703:787	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	5	2	theme	transcriptome	722:734	arg1	transcriptome					722:734	the UGT2B10 transcriptome	710:734	the UGT2B10 transcriptome	710:734	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	7	3	theme	novel	907:911	arg1	termini					924:930	novel in-frame C termini	907:930	novel in-frame C termini of 10 or 65 amino acids	907:954	variants with novel in-frame C termini of 10 or 65 amino acids.
29438977	11	4	theme	turnover	1403:1410	arg1	rate					1412:1415	A high turnover rate	1396:1415	A high turnover rate for the alt	1396:1427	A high turnover rate for the alt.
29438977	1	5	theme	drugs	217:221	arg1	glucuronidation					193:207	the N-linked glucuronidation	180:207	the N-linked glucuronidation of many drugs and xenobiotics	180:237	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	8	6	theme	canonical	1037:1045	arg1	levels					1058:1063	canonical transcript levels	1037:1063	canonical transcript levels	1037:1063	Their hepatic expression was highly variable among individuals, correlated with canonical transcript levels, and was 3.5-fold higher in tumors.
29438977	6	7	theme	exonic	841:846	arg1	sequence					848:855	a novel exonic sequence	833:855	a novel exonic sequence	833:855	One abundant class of transcripts involves a novel exonic sequence and leads to two alternative (alt.)
29438977	1	8	theme	xenobiotics	227:237	arg1	glucuronidation					193:207	the N-linked glucuronidation	180:207	the N-linked glucuronidation of many drugs and xenobiotics	180:237	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	2	9	theme	tertiary	269:276	arg1	amines					288:293	tertiary aliphatic amines	269:293	tertiary aliphatic amines	269:293	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	9	theme	tertiary	269:276	arg1	antidepressants					360:374	antidepressants	360:374	antidepressants	360:374	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	9	theme	tertiary	269:276	arg1	carcinogens					336:346	tobacco carcinogens	328:346	tobacco carcinogens	328:346	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	5	10	theme	highest	630:636	arg1	expression					638:647	The highest expression	626:647	The highest expression	626:647	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	2	11	theme	several	352:358	arg1	antidepressants					360:374	antidepressants	360:374	antidepressants	360:374	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	12	contain	possess	261:267	arg2	amines					312:317	heterocyclic amines	299:317	heterocyclic amines	299:317	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	12	contain	possess	261:267	arg2	carcinogens					336:346	tobacco carcinogens	328:346	tobacco carcinogens	328:346	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	12	contain	possess	261:267	arg1	substrates					250:259	Preferred substrates	240:259	Preferred substrates	240:259	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	12	contain	possess	261:267	arg2	antidepressants					360:374	antidepressants	360:374	antidepressants	360:374	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	12	contain	possess	261:267	arg2	amines					288:293	tertiary aliphatic amines	269:293	tertiary aliphatic amines	269:293	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	15	13	from	regulation	1767:1776	arg1	liver					1807:1811	the liver	1803:1811	the liver with an impact on enzyme activity	1803:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	10	14	dep	%	1348:1348	arg1	<					1353:1353	P < 0.01	1351:1358	P < 0.01	1351:1358	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	10	15	theme	amitriptyline	1267:1279	arg1	conjugation					1252:1262	the conjugation	1248:1262	the conjugation of amitriptyline and levomedetomidine	1248:1300	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	15	16	theme	significant	1729:1739	arg1	contribution					1741:1752	a significant contribution	1727:1752	a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity	1727:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	2	17	theme	heterocyclic	299:310	arg1	carcinogens					336:346	tobacco carcinogens	328:346	tobacco carcinogens	328:346	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	17	theme	heterocyclic	299:310	arg1	amines					312:317	heterocyclic amines	299:317	heterocyclic amines	299:317	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	17	theme	heterocyclic	299:310	arg1	antidepressants					360:374	antidepressants	360:374	antidepressants	360:374	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	1	18	theme	N-linked	184:191	arg1	glucuronidation					193:207	the N-linked glucuronidation	180:207	the N-linked glucuronidation of many drugs and xenobiotics	180:237	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	10	19	theme	levomedetomidine	1285:1300	arg1	conjugation					1252:1262	the conjugation	1248:1262	the conjugation of amitriptyline and levomedetomidine	1248:1300	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	10	20	theme	%	1344:1344	arg1	enzyme					1334:1339	the enzyme	1330:1339	the enzyme (40%-70%; P < 0.01)	1330:1359	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	10	20	theme	%	1344:1344	arg1	%					1348:1348	40%-70%	1342:1348	40%-70%	1342:1348	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	12	21	theme	UGT2B10	1513:1519	arg1	enzyme					1521:1526	the more stable UGT2B10 enzyme	1497:1526	the more stable UGT2B10 enzyme	1497:1526	proteins, regulated by the proteasome, was observed in contrast to the more stable UGT2B10 enzyme.
29438977	3	22	theme	alternative	417:427	arg1	splicing					429:436	alternative splicing	417:436	alternative splicing (AS)	417:441	We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels of UGT2B10 and enzyme activity.
29438977	15	23	theme	UGT2B10	1781:1787	arg1	expression					1789:1798	UGT2B10 expression	1781:1798	UGT2B10 expression	1781:1798	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	0	24	theme	Post-transcriptional	0:19	arg1	Regulation					21:30	Post-transcriptional Regulation	0:30	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.	0:98	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.
29438977	1	25	theme	detoxification	104:117	arg1	UGT2B10					154:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10	100:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10	100:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	1	26	theme	UDP-glucuronosyltransferase	126:152	arg1	UGT2B10					154:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10	100:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10	100:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	3	27	theme	steady-state	475:486	arg1	levels					488:493	steady-state levels	475:493	steady-state levels of UGT2B10 and enzyme activity	475:524	We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels of UGT2B10 and enzyme activity.
29438977	3	28	theme	activity	517:524	arg1	levels					488:493	steady-state levels	475:493	steady-state levels of UGT2B10 and enzyme activity	475:524	We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels of UGT2B10 and enzyme activity.
29438977	0	29	theme	Hepatic	43:49	arg1	Expression					51:60	UGT2B10 Hepatic Expression	35:60	UGT2B10 Hepatic Expression	35:60	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.
29438977	15	30	with	liver	1807:1811	arg1	impact					1821:1826	an impact	1818:1826	an impact on enzyme activity	1818:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	9	31	theme	mass	1165:1168	arg1	spectrometry					1170:1181	mass spectrometry	1165:1181	mass spectrometry	1165:1181	Evidence for their translation in liver tissues was acquired by mass spectrometry.
29438977	10	32	theme	cell	1187:1190	arg1	models					1192:1197	cell models	1187:1197	cell models	1187:1197	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	7	33	with	variants	893:900	arg1	termini					924:930	novel in-frame C termini	907:930	novel in-frame C termini of 10 or 65 amino acids	907:954	variants with novel in-frame C termini of 10 or 65 amino acids.
29438977	4	34	theme	multiple	604:611	arg1	individuals					613:623	multiple individuals	604:623	multiple individuals	604:623	We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals.
29438977	13	35	theme	hepatic	1616:1622	arg1	model					1629:1633	the HepaRG hepatic cell model	1605:1633	the HepaRG hepatic cell model	1605:1633	Moreover, a drug-induced remodeling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt.
29438977	9	36	from	translation	1120:1130	arg1	tissues					1141:1147	liver tissues	1135:1147	liver tissues	1135:1147	Evidence for their translation in liver tissues was acquired by mass spectrometry.
29438977	7	37	theme	acids	950:954	arg1	termini					924:930	novel in-frame C termini	907:930	novel in-frame C termini of 10 or 65 amino acids	907:954	variants with novel in-frame C termini of 10 or 65 amino acids.
29438977	15	38	theme	enzyme	1831:1836	arg1	activity					1838:1845	enzyme activity	1831:1845	enzyme activity	1831:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	6	39	theme	abundant	794:801	arg1	class					803:807	One abundant class	790:807	One abundant class of transcripts	790:822	One abundant class of transcripts involves a novel exonic sequence and leads to two alternative (alt.)
29438977	5	40	theme	UGT2B10	714:720	arg1	transcriptome					722:734	the UGT2B10 transcriptome	710:734	the UGT2B10 transcriptome	710:734	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	13	41	theme	splicing	1576:1583	arg1	remodeling					1554:1563	a drug-induced remodeling	1539:1563	a drug-induced remodeling of UGT2B10 splicing	1539:1583	Moreover, a drug-induced remodeling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt.
29438977	12	42	located	observed	1473:1480	arg1	contrast					1485:1492	contrast	1485:1492	contrast to the more stable UGT2B10 enzyme	1485:1526	proteins, regulated by the proteasome, was observed in contrast to the more stable UGT2B10 enzyme.
29438977	12	42	located	observed	1473:1480	arg2	proteins					1430:1437	proteins	1430:1437	proteins	1430:1437	proteins, regulated by the proteasome, was observed in contrast to the more stable UGT2B10 enzyme.
29438977	11	43	theme	high	1398:1401	arg1	rate					1412:1415	A high turnover rate	1396:1415	A high turnover rate for the alt	1396:1427	A high turnover rate for the alt.
29438977	10	44	theme	context-specific	1371:1386	arg1	manner					1388:1393	a cell context-specific manner	1364:1393	a cell context-specific manner	1364:1393	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	2	45	theme	tobacco	328:334	arg1	carcinogens					336:346	tobacco carcinogens	328:346	tobacco carcinogens	328:346	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	7	46	theme	in-frame	913:920	arg1	termini					924:930	novel in-frame C termini	907:930	novel in-frame C termini of 10 or 65 amino acids	907:954	variants with novel in-frame C termini of 10 or 65 amino acids.
29438977	1	47	theme	many	212:215	arg1	drugs					217:221	many drugs	212:221	many drugs	212:221	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	8	48	theme	transcript	1047:1056	arg1	levels					1058:1063	canonical transcript levels	1037:1063	canonical transcript levels	1037:1063	Their hepatic expression was highly variable among individuals, correlated with canonical transcript levels, and was 3.5-fold higher in tumors.
29438977	4	49	from	transcriptome	546:558	arg1	tissues					593:599	normal and tumoral tissues	574:599	normal and tumoral tissues of multiple individuals	574:623	We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals.
29438977	13	50	theme	drug-induced	1541:1552	arg1	remodeling					1554:1563	a drug-induced remodeling	1539:1563	a drug-induced remodeling of UGT2B10 splicing	1539:1583	Moreover, a drug-induced remodeling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt.
29438977	3	51	dep	splicing	429:436	arg1	AS					439:440	AS	439:440	AS	439:440	We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels of UGT2B10 and enzyme activity.
29438977	6	52	theme	novel	835:839	arg1	sequence					848:855	a novel exonic sequence	833:855	a novel exonic sequence	833:855	One abundant class of transcripts involves a novel exonic sequence and leads to two alternative (alt.)
29438977	15	53	from	contribution	1741:1752	arg1	regulation					1767:1776	the regulation	1763:1776	the regulation of UGT2B10 expression in the liver with an impact on enzyme activity	1763:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	6	54	theme	transcripts	812:822	arg1	class					803:807	One abundant class	790:807	One abundant class of transcripts	790:822	One abundant class of transcripts involves a novel exonic sequence and leads to two alternative (alt.)
29438977	5	55	theme	hepatocellular	763:776	arg1	carcinomas					778:787	44 hepatocellular carcinomas	760:787	44 hepatocellular carcinomas	760:787	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	14	56	theme	canonical	1684:1692	arg1	transcript					1694:1703	the canonical transcript	1680:1703	the canonical transcript	1680:1703	variants expression over the canonical transcript.
29438977	2	57	theme	aliphatic	278:286	arg1	amines					288:293	tertiary aliphatic amines	269:293	tertiary aliphatic amines	269:293	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	57	theme	aliphatic	278:286	arg1	antidepressants					360:374	antidepressants	360:374	antidepressants	360:374	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	2	57	theme	aliphatic	278:286	arg1	carcinogens					336:346	tobacco carcinogens	328:346	tobacco carcinogens	328:346	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	5	58	theme	normal	742:747	arg1	livers					749:754	50 normal livers	739:754	50 normal livers	739:754	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	0	59	theme	Alternative	78:88	arg1	Splicing					90:97	Alternative Splicing	78:97	Alternative Splicing	78:97	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.
29438977	4	60	theme	normal	574:579	arg1	tissues					593:599	normal and tumoral tissues	574:599	normal and tumoral tissues of multiple individuals	574:623	We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals.
29438977	12	61	theme	stable	1506:1511	arg1	enzyme					1521:1526	the more stable UGT2B10 enzyme	1497:1526	the more stable UGT2B10 enzyme	1497:1526	proteins, regulated by the proteasome, was observed in contrast to the more stable UGT2B10 enzyme.
29438977	4	62	theme	tumoral	585:591	arg1	tissues					593:599	normal and tumoral tissues	574:599	normal and tumoral tissues of multiple individuals	574:623	We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals.
29438977	13	63	theme	UGT2B10	1568:1574	arg1	splicing					1576:1583	UGT2B10 splicing	1568:1583	UGT2B10 splicing	1568:1583	Moreover, a drug-induced remodeling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt.
29438977	15	64	theme	expression	1789:1798	arg1	regulation					1767:1776	the regulation	1763:1776	the regulation of UGT2B10 expression in the liver with an impact on enzyme activity	1763:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	5	65	theme	AS	676:677	arg1	transcripts					679:689	10 AS transcripts	673:689	10 AS transcripts	673:689	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	4	66	theme	UGT2B10	563:569	arg1	transcriptome					546:558	the transcriptome	542:558	the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals	542:623	We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals.
29438977	3	67	theme	enzyme	510:515	arg1	activity					517:524	enzyme activity	510:524	enzyme activity	510:524	We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels of UGT2B10 and enzyme activity.
29438977	9	68	theme	liver	1135:1139	arg1	tissues					1141:1147	liver tissues	1135:1147	liver tissues	1135:1147	Evidence for their translation in liver tissues was acquired by mass spectrometry.
29438977	3	69	theme	UGT2B10	498:504	arg1	levels					488:493	steady-state levels	475:493	steady-state levels of UGT2B10 and enzyme activity	475:524	We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels of UGT2B10 and enzyme activity.
29438977	0	70	theme	UGT2B10	35:41	arg1	Expression					51:60	UGT2B10 Hepatic Expression	35:60	UGT2B10 Hepatic Expression	35:60	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.
29438977	5	71	from	%	705:705	arg1	livers					749:754	50 normal livers	739:754	50 normal livers	739:754	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	5	71	from	%	705:705	arg1	carcinomas					778:787	44 hepatocellular carcinomas	760:787	44 hepatocellular carcinomas	760:787	The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas.
29438977	1	72	theme	enzyme	119:124	arg1	UGT2B10					154:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10	100:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10	100:160	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	15	73	theme	AS	1757:1758	arg1	contribution					1741:1752	a significant contribution	1727:1752	a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity	1727:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	0	74	theme	Expression	51:60	arg1	Regulation					21:30	Post-transcriptional Regulation	0:30	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.	0:98	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.
29438977	1	75	link	N-linked	184:191	arg1	glucuronidation					193:207	the N-linked glucuronidation	180:207	the N-linked glucuronidation of many drugs and xenobiotics	180:237	The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics.
29438977	0	76	theme	Activity	66:73	arg1	Regulation					21:30	Post-transcriptional Regulation	0:30	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.	0:98	Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing.
29438977	4	77	theme	individuals	613:623	arg1	tissues					593:599	normal and tumoral tissues	574:599	normal and tumoral tissues of multiple individuals	574:623	We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals.
29438977	13	78	theme	HepaRG	1609:1614	arg1	model					1629:1633	the HepaRG hepatic cell model	1605:1633	the HepaRG hepatic cell model	1605:1633	Moreover, a drug-induced remodeling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt.
29438977	15	79	from	impact	1821:1826	arg1	activity					1838:1845	enzyme activity	1831:1845	enzyme activity	1831:1845	Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.
29438977	10	80	theme	P	1351:1351	arg1	<					1353:1353	P < 0.01	1351:1358	P < 0.01	1351:1358	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29438977	7	81	theme	amino	944:948	arg1	acids					950:954	10 or 65 amino acids	935:954	10 or 65 amino acids	935:954	variants with novel in-frame C termini of 10 or 65 amino acids.
29438977	8	82	theme	hepatic	963:969	arg1	expression					971:980	Their hepatic expression	957:980	Their hepatic expression	957:980	Their hepatic expression was highly variable among individuals, correlated with canonical transcript levels, and was 3.5-fold higher in tumors.
29438977	13	83	theme	cell	1624:1627	arg1	model					1629:1633	the HepaRG hepatic cell model	1605:1633	the HepaRG hepatic cell model	1605:1633	Moreover, a drug-induced remodeling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt.
29438977	2	84	theme	Preferred	240:248	arg1	substrates					250:259	Preferred substrates	240:259	Preferred substrates	240:259	Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics.
29438977	10	85	theme	cell	1366:1369	arg1	manner					1388:1393	a cell context-specific manner	1364:1393	a cell context-specific manner	1364:1393	In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%-70%; P < 0.01) in a cell context-specific manner.
29045152	5	0	theme	hybrids	794:800	arg1	discovery					753:761	the discovery	749:761	the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s)	749:908	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	6	1	theme	plasma	1041:1046	arg1	values					1058:1063	the observed plasma clearance values	1028:1063	the observed plasma clearance values upon intravenous administration	1028:1095	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	4	2	theme	theoretical	579:589	arg1	calculations					591:602	theoretical calculations	579:602	theoretical calculations	579:602	At the same time, theoretical calculations and experimental assays were used to track and reduce the polarity while closely monitoring the physicochemical properties.
29045152	0	3	theme	Modulators	85:94	arg1	Discovery					0:8	Discovery	0:8	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.	0:95	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.
29045152	6	4	from	bioavailability	968:982	arg1	rats					994:997	rats	994:997	rats	994:997	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	4	5	theme	physicochemical	700:714	arg1	properties					716:725	the physicochemical properties	696:725	the physicochemical properties	696:725	At the same time, theoretical calculations and experimental assays were used to track and reduce the polarity while closely monitoring the physicochemical properties.
29045152	6	6	with	commensurate	1010:1021	arg1	values					1058:1063	the observed plasma clearance values	1028:1063	the observed plasma clearance values upon intravenous administration	1028:1095	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	5	7	theme	binding	818:824	arg1	nM					847:848	Ki < 100 nM	838:848	Ki < 100 nM	838:848	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	7	theme	binding	818:824	arg1	affinities					826:835	high CXCR7 binding affinities	807:835	high CXCR7 binding affinities (Ki < 100 nM)	807:849	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	6	8	theme	=	946:946	arg1	peptide					931:937	bioactive peptide 25	921:940	bioactive peptide 25 (Ki = 9 nM)	921:952	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	6	8	theme	=	946:946	arg1	nM					950:951	Ki = 9 nM	943:951	Ki = 9 nM	943:951	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	5	9	theme	passive	866:872	arg1	permeability					874:885	measurable passive permeability	855:885	measurable passive permeability (Papp > 5 × 10-6 cm/s)	855:908	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	3	10	theme	side-chain	499:508	arg1	diversity					510:518	side-chain diversity	499:518	side-chain diversity well beyond that of natural amino acids	499:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	3	11	theme	natural	540:546	arg1	acids					554:558	natural amino acids	540:558	natural amino acids	540:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	1	12	theme	diseases	167:174	arg1	diseases					167:174	diseases	167:174	diseases	167:174	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	1	12	theme	diseases	167:174	arg1	variety					156:162	a variety	154:162	a variety of diseases	154:174	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	5	13	theme	high	807:810	arg1	nM					847:848	Ki < 100 nM	838:848	Ki < 100 nM	838:848	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	13	theme	high	807:810	arg1	affinities					826:835	high CXCR7 binding affinities	807:835	high CXCR7 binding affinities (Ki < 100 nM)	807:849	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	3	14	theme	amino	548:552	arg1	acids					554:558	natural amino acids	540:558	natural amino acids	540:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	6	15	theme	observed	1032:1039	arg1	values					1058:1063	the observed plasma clearance values	1028:1063	the observed plasma clearance values upon intravenous administration	1028:1095	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	3	16	theme	peptidic	381:388	arg1	macrocycles					390:400	peptidic macrocycles	381:400	peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids	381:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	5	17	theme	macrocyclic	766:776	arg1	hybrids					794:800	macrocyclic peptide-peptoid hybrids	766:800	macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s)	766:908	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	3	18	dep	well	520:523	arg1	beyond					525:530	beyond	525:530	beyond	525:530	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	3	19	theme	peptoid	431:437	arg1	functionality					439:451	an N-linked peptoid functionality	419:451	an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids	419:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	3	20	theme	macrocycles	390:400	arg1	series					371:376	a series	369:376	a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids	369:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	2	21	theme	selectivity	311:321	arg1	terms					293:297	terms	293:297	terms of potency, selectivity, and reduced off-target activity	293:354	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	6	22	theme	oral	963:966	arg1	bioavailability					968:982	oral bioavailability	963:982	oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration	963:1095	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	4	23	theme	experimental	608:619	arg1	assays					621:626	experimental assays	608:626	experimental assays	608:626	At the same time, theoretical calculations and experimental assays were used to track and reduce the polarity while closely monitoring the physicochemical properties.
29045152	5	24	theme	Ki	838:839	arg1	nM					847:848	Ki < 100 nM	838:848	Ki < 100 nM	838:848	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	24	theme	Ki	838:839	arg1	affinities					826:835	high CXCR7 binding affinities	807:835	high CXCR7 binding affinities (Ki < 100 nM)	807:849	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	25	dep	permeability	874:885	arg1	Papp					888:891	Papp	888:891	Papp	888:891	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	1	26	theme	receptor	111:118	arg1	target					143:148	an attractive target	129:148	an attractive target for a variety of diseases	129:174	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	1	26	theme	receptor	111:118	arg1	CXCR7					120:124	The chemokine receptor CXCR7	97:124	The chemokine receptor CXCR7	97:124	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	1	27	theme	chemokine	101:109	arg1	target					143:148	an attractive target	129:148	an attractive target for a variety of diseases	129:174	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	1	27	theme	chemokine	101:109	arg1	CXCR7					120:124	The chemokine receptor CXCR7	97:124	The chemokine receptor CXCR7	97:124	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	6	28	theme	Ki	943:944	arg1	peptide					931:937	bioactive peptide 25	921:940	bioactive peptide 25 (Ki = 9 nM)	921:952	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	6	28	theme	Ki	943:944	arg1	nM					950:951	Ki = 9 nM	943:951	Ki = 9 nM	943:951	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	4	29	used	used	633:636	arg2	assays					621:626	experimental assays	608:626	experimental assays	608:626	At the same time, theoretical calculations and experimental assays were used to track and reduce the polarity while closely monitoring the physicochemical properties.
29045152	4	29	used	used	633:636	arg2	calculations					591:602	theoretical calculations	579:602	theoretical calculations	579:602	At the same time, theoretical calculations and experimental assays were used to track and reduce the polarity while closely monitoring the physicochemical properties.
29045152	2	30	theme	several	183:189	arg1	modulators					206:215	several small-molecule modulators	183:215	several small-molecule modulators of CXCR7	183:224	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	2	31	theme	potency	302:308	arg1	terms					293:297	terms	293:297	terms of potency, selectivity, and reduced off-target activity	293:354	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	0	32	theme	Bioavailable	31:42	arg1	Modulators					85:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.
29045152	4	33	theme	same	568:571	arg1	time					573:576	the same time	564:576	the same time	564:576	At the same time, theoretical calculations and experimental assays were used to track and reduce the polarity while closely monitoring the physicochemical properties.
29045152	3	34	theme	peptoid	463:469	arg1	group					471:475	the peptoid group	459:475	the peptoid group	459:475	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	0	35	theme	Potent	13:18	arg1	Modulators					85:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.
29045152	3	36	theme	N-linked	422:429	arg1	functionality					439:451	an N-linked peptoid functionality	419:451	an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids	419:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	5	37	theme	<	841:841	arg1	nM					847:848	Ki < 100 nM	838:848	Ki < 100 nM	838:848	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	37	theme	<	841:841	arg1	affinities					826:835	high CXCR7 binding affinities	807:835	high CXCR7 binding affinities (Ki < 100 nM)	807:849	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	38	theme	measurable	855:864	arg1	permeability					874:885	measurable passive permeability	855:885	measurable passive permeability (Papp > 5 × 10-6 cm/s)	855:908	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	0	39	theme	Peptide-Peptoid	56:70	arg1	Modulators					85:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.
29045152	5	40	theme	peptide-peptoid	778:792	arg1	hybrids					794:800	macrocyclic peptide-peptoid hybrids	766:800	macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s)	766:908	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	6	41	theme	intravenous	1070:1080	arg1	administration					1082:1095	intravenous administration	1070:1095	intravenous administration	1070:1095	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	2	42	theme	activity	347:354	arg1	terms					293:297	terms	293:297	terms of potency, selectivity, and reduced off-target activity	293:354	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	0	43	theme	Macrocyclic	44:54	arg1	Modulators					85:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.
29045152	6	44	theme	bioactive	921:929	arg1	peptide					931:937	bioactive peptide 25	921:940	bioactive peptide 25 (Ki = 9 nM)	921:952	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	6	44	theme	bioactive	921:929	arg1	nM					950:951	Ki = 9 nM	943:951	Ki = 9 nM	943:951	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	2	45	theme	CXCR7	220:224	arg1	modulators					206:215	several small-molecule modulators	183:215	several small-molecule modulators of CXCR7	183:224	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	3	46	link	N-linked	422:429	arg1	functionality					439:451	an N-linked peptoid functionality	419:451	an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids	419:558	We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side-chain diversity well beyond that of natural amino acids.
29045152	2	47	theme	off-target	336:345	arg1	activity					347:354	reduced off-target activity	328:354	reduced off-target activity	328:354	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	5	48	with	hybrids	794:800	arg1	permeability					874:885	measurable passive permeability	855:885	measurable passive permeability (Papp > 5 × 10-6 cm/s)	855:908	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	48	with	hybrids	794:800	arg1	nM					847:848	Ki < 100 nM	838:848	Ki < 100 nM	838:848	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	48	with	hybrids	794:800	arg1	affinities					826:835	high CXCR7 binding affinities	807:835	high CXCR7 binding affinities (Ki < 100 nM)	807:849	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	49	theme	CXCR7	812:816	arg1	nM					847:848	Ki < 100 nM	838:848	Ki < 100 nM	838:848	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	49	theme	CXCR7	812:816	arg1	affinities					826:835	high CXCR7 binding affinities	807:835	high CXCR7 binding affinities (Ki < 100 nM)	807:849	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	5	50	dep	Papp	888:891	arg1	cm/s					904:907	5 × 10-6 cm/s	895:907	Papp > 5 × 10-6 cm/s	888:907	This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability (Papp > 5 × 10-6 cm/s).
29045152	1	51	theme	attractive	132:141	arg1	target					143:148	an attractive target	129:148	an attractive target for a variety of diseases	129:174	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	1	51	theme	attractive	132:141	arg1	CXCR7					120:124	The chemokine receptor CXCR7	97:124	The chemokine receptor CXCR7	97:124	The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
29045152	6	52	theme	%	989:989	arg1	bioavailability					968:982	oral bioavailability	963:982	oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration	963:1095	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29045152	2	53	theme	reduced	328:334	arg1	activity					347:354	reduced off-target activity	328:354	reduced off-target activity	328:354	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	0	54	theme	CXCR7	79:83	arg1	Modulators					85:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.
29045152	2	55	theme	small-molecule	191:204	arg1	modulators					206:215	several small-molecule modulators	183:215	several small-molecule modulators of CXCR7	183:224	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	0	56	theme	Hybrid	72:77	arg1	Modulators					85:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators	13:94	Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid CXCR7 Modulators.
29045152	2	57	theme	peptidic	246:253	arg1	macrocycles					255:265	peptidic macrocycles	246:265	peptidic macrocycles	246:265	While several small-molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity.
29045152	6	58	theme	clearance	1048:1056	arg1	values					1058:1063	the observed plasma clearance values	1028:1063	the observed plasma clearance values upon intravenous administration	1028:1095	Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral bioavailability of 18% in rats, which was commensurate with the observed plasma clearance values upon intravenous administration.
29950701	8	0	theme	mortality	1157:1165	arg1	predictor					1144:1152	a superior predictor	1133:1152	a superior predictor of mortality	1133:1165	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	0	theme	mortality	1157:1165	arg1	concentrations					1113:1126	persistently elevated BSP concentrations	1087:1126	persistently elevated BSP concentrations	1087:1126	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	7	1	theme	BSP	1023:1025	arg1	levels					1027:1032	persistently elevated BSP levels	1001:1032	persistently elevated BSP levels	1001:1032	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	6	2	with	patients	808:815	arg1	APACHE-II-scores					829:844	higher APACHE-II-scores	822:844	higher APACHE-II-scores	822:844	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	0	3	theme	long-term	72:80	arg1	mortality					82:90	long-term mortality	72:90	long-term mortality in critically ill patients	72:117	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	6	4	theme	higher	822:827	arg1	APACHE-II-scores					829:844	higher APACHE-II-scores	822:844	higher APACHE-II-scores	822:844	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	2	5	theme	BSP	328:330	arg1	concentrations					332:345	BSP concentrations	328:345	BSP concentrations	328:345	We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU.
29950701	1	6	theme	family	230:235	arg1	sialoprotein					125:136	Bone sialoprotein	120:136	Bone sialoprotein (BSP)	120:142	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	1	6	theme	family	230:235	arg1	member					147:152	a member	145:152	a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family	145:235	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	7	7	theme	elevated	1014:1021	arg1	levels					1027:1032	persistently elevated BSP levels	1001:1032	persistently elevated BSP levels	1001:1032	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	7	8	theme	unfavorable	1047:1057	arg1	outcome					1059:1065	an unfavorable outcome	1044:1065	an unfavorable outcome	1044:1065	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	8	9	theme	APACHE-II	1242:1250	arg1	score					1252:1256	the APACHE-II score	1238:1256	the APACHE-II score	1238:1256	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	4	10	theme	healthy	631:637	arg1	controls					639:646	healthy controls	631:646	healthy controls	631:646	In these analysis, BSP serum levels were strongly elevated at the time point of admission to the ICU when compared to healthy controls.
29950701	5	11	theme	BSP	658:660	arg1	concentrations					662:675	BSP concentrations	658:675	BSP concentrations	658:675	Moreover BSP concentrations were significantly elevated after 3 days of treatment on the intensive care unit.
29950701	9	12	theme	novel	1292:1296	arg1	utility					1298:1304	a novel utility	1290:1304	a novel utility for BSP as a biomarker in patients treated on a medical ICU	1290:1364	In summary, our data argue for a novel utility for BSP as a biomarker in patients treated on a medical ICU.
29950701	8	13	theme	established	1172:1182	arg1	indicators					1184:1193	established indicators	1172:1193	established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score	1172:1256	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	13	theme	established	1172:1182	arg1	score					1252:1256	the APACHE-II score	1238:1256	the APACHE-II score	1238:1256	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	13	theme	established	1172:1182	arg1	SAPS2					1229:1233	SAPS2	1229:1233	SAPS2	1229:1233	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	3	14	theme	blood	467:471	arg1	donors					473:478	36 healthy blood donors	456:478	36 healthy blood donors	456:478	BSP levels were compared to 36 healthy blood donors and correlated to clinical data.
29950701	0	15	theme	ill	106:108	arg1	patients					110:117	critically ill patients	95:117	critically ill patients	95:117	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	2	16	theme	ICU	423:425	arg1	admission					366:374	admission	366:374	admission to the intensive care unit (ICU)	366:407	We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU.
29950701	2	16	theme	ICU	423:425	arg1	days					415:418	3 days	413:418	3 days of ICU	413:425	We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU.
29950701	1	17	link	N-linked	206:213	arg1	Glycoproteins					215:227	N-linked Glycoproteins	206:227	N-linked Glycoproteins	206:227	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	1	17	link	N-linked	206:213	arg1	SIBLINGs					161:168	SIBLINGs	161:168	the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family	157:235	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	6	18	from	increase	769:776	arg1	levels					785:790	BSP levels	781:790	BSP levels	781:790	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	4	19	theme	time	579:582	arg1	point					584:588	the time point	575:588	the time point of admission to the ICU	575:612	In these analysis, BSP serum levels were strongly elevated at the time point of admission to the ICU when compared to healthy controls.
29950701	0	20	theme	serum	9:13	arg1	levels					15:20	Elevated serum levels	0:20	Elevated serum levels of bone sialoprotein during ICU treatment	0:62	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	6	21	with	patients	853:860	arg1	disease					874:880	septic disease	867:880	septic disease	867:880	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	4	22	theme	admission	593:601	arg1	point					584:588	the time point	575:588	the time point of admission to the ICU	575:612	In these analysis, BSP serum levels were strongly elevated at the time point of admission to the ICU when compared to healthy controls.
29950701	0	23	theme	Elevated	0:7	arg1	levels					15:20	Elevated serum levels	0:20	Elevated serum levels of bone sialoprotein during ICU treatment	0:62	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	1	24	theme	SIBLINGs	161:168	arg1	family					230:235	the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family	157:235	the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family	157:235	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	5	25	theme	intensive	738:746	arg1	unit					753:756	the intensive care unit	734:756	the intensive care unit	734:756	Moreover BSP concentrations were significantly elevated after 3 days of treatment on the intensive care unit.
29950701	5	26	theme	care	748:751	arg1	unit					753:756	the intensive care unit	734:756	the intensive care unit	734:756	Moreover BSP concentrations were significantly elevated after 3 days of treatment on the intensive care unit.
29950701	7	27	theme	medical	974:980	arg1	ICU					982:984	a medical ICU	972:984	a medical ICU	972:984	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	0	28	from	mortality	82:90	arg1	patients					110:117	critically ill patients	95:117	critically ill patients	95:117	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	3	29	theme	clinical	498:505	arg1	data					507:510	clinical data	498:510	clinical data	498:510	BSP levels were compared to 36 healthy blood donors and correlated to clinical data.
29950701	2	30	theme	care	393:396	arg1	ICU					404:406	ICU	404:406	ICU	404:406	We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU.
29950701	2	30	theme	care	393:396	arg1	unit					398:401	the intensive care unit	379:401	the intensive care unit (ICU)	379:407	We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU.
29950701	0	31	theme	sialoprotein	30:41	arg1	levels					15:20	Elevated serum levels	0:20	Elevated serum levels of bone sialoprotein during ICU treatment	0:62	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	8	32	theme	prognosis	1207:1215	arg1	indicators					1184:1193	established indicators	1172:1193	established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score	1172:1256	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	32	theme	prognosis	1207:1215	arg1	score					1252:1256	the APACHE-II score	1238:1256	the APACHE-II score	1238:1256	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	32	theme	prognosis	1207:1215	arg1	SAPS2					1229:1233	SAPS2	1229:1233	SAPS2	1229:1233	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	7	33	theme	treatment	959:967	arg1	days					951:954	the first three days	935:954	the first three days of treatment	935:967	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	1	34	theme	Small	175:179	arg1	LIgand					198:203	Small Integrin-Binding LIgand	175:203	Small Integrin-Binding LIgand	175:203	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	6	35	located	detected	796:803	arg1	patients					808:815	patients	808:815	patients with higher APACHE-II-scores	808:844	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	6	35	located	detected	796:803	arg2	increase					769:776	A further increase	759:776	A further increase in BSP levels	759:790	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	2	36	theme	intensive	383:391	arg1	ICU					404:406	ICU	404:406	ICU	404:406	We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU.
29950701	2	36	theme	intensive	383:391	arg1	unit					398:401	the intensive care unit	379:401	the intensive care unit (ICU)	379:407	We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU.
29950701	0	37	theme	bone	25:28	arg1	sialoprotein					30:41	bone sialoprotein	25:41	bone sialoprotein	25:41	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	6	38	theme	septic	867:872	arg1	disease					874:880	septic disease	867:880	septic disease	867:880	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	8	39	theme	patient´	1198:1205	arg1	prognosis					1207:1215	patient´ prognosis	1198:1215	patient´ prognosis	1198:1215	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	40	theme	BSP	1109:1111	arg1	predictor					1144:1152	a superior predictor	1133:1152	a superior predictor of mortality	1133:1165	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	40	theme	BSP	1109:1111	arg1	concentrations					1113:1126	persistently elevated BSP concentrations	1087:1126	persistently elevated BSP concentrations	1087:1126	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	1	41	theme	Integrin-Binding	181:196	arg1	LIgand					198:203	Small Integrin-Binding LIgand	175:203	Small Integrin-Binding LIgand	175:203	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	0	42	theme	ICU	50:52	arg1	treatment					54:62	ICU treatment	50:62	ICU treatment	50:62	Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients.
29950701	9	43	theme	medical	1354:1360	arg1	ICU					1362:1364	a medical ICU	1352:1364	a medical ICU	1352:1364	In summary, our data argue for a novel utility for BSP as a biomarker in patients treated on a medical ICU.
29950701	5	44	theme	treatment	721:729	arg1	days					713:716	3 days	711:716	3 days of treatment	711:729	Moreover BSP concentrations were significantly elevated after 3 days of treatment on the intensive care unit.
29950701	1	45	theme	infectious	285:294	arg1	diseases					296:303	infectious diseases	285:303	infectious diseases	285:303	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	6	46	theme	further	761:767	arg1	increase					769:776	A further increase	759:776	A further increase in BSP levels	759:790	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	8	47	dep	SAPS2	1229:1233	arg1	the					1225:1227	the	1225:1227	the	1225:1227	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	1	48	theme	Bone	120:123	arg1	sialoprotein					125:136	Bone sialoprotein	120:136	Bone sialoprotein (BSP)	120:142	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	1	48	theme	Bone	120:123	arg1	member					147:152	a member	145:152	a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family	145:235	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	1	48	theme	Bone	120:123	arg1	BSP					139:141	BSP	139:141	BSP	139:141	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	7	49	theme	first	939:943	arg1	days					951:954	the first three days	935:954	the first three days of treatment	935:967	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	8	50	from	predictor	1144:1152	arg1	patients					1077:1084	these patients	1071:1084	these patients	1071:1084	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	7	51	with	patients	987:994	arg1	levels					1027:1032	persistently elevated BSP levels	1001:1032	persistently elevated BSP levels	1001:1032	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	9	52	from	biomarker	1319:1327	arg1	patients					1332:1339	patients	1332:1339	patients treated on a medical ICU	1332:1364	In summary, our data argue for a novel utility for BSP as a biomarker in patients treated on a medical ICU.
29950701	4	53	theme	serum	536:540	arg1	levels					542:547	BSP serum levels	532:547	BSP serum levels	532:547	In these analysis, BSP serum levels were strongly elevated at the time point of admission to the ICU when compared to healthy controls.
29950701	3	54	theme	BSP	428:430	arg1	levels					432:437	BSP levels	428:437	BSP levels	428:437	BSP levels were compared to 36 healthy blood donors and correlated to clinical data.
29950701	4	55	theme	BSP	532:534	arg1	levels					542:547	BSP serum levels	532:547	BSP serum levels	532:547	In these analysis, BSP serum levels were strongly elevated at the time point of admission to the ICU when compared to healthy controls.
29950701	6	56	theme	BSP	781:783	arg1	levels					785:790	BSP levels	781:790	BSP levels	781:790	A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease.
29950701	7	57	theme	BSP	907:909	arg1	levels					911:916	BSP levels	907:916	BSP levels	907:916	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	1	58	theme	N-linked	206:213	arg1	Glycoproteins					215:227	N-linked Glycoproteins	206:227	N-linked Glycoproteins	206:227	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	1	58	theme	N-linked	206:213	arg1	SIBLINGs					161:168	SIBLINGs	161:168	the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family	157:235	Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases.
29950701	8	59	theme	superior	1135:1142	arg1	predictor					1144:1152	a superior predictor	1133:1152	a superior predictor of mortality	1133:1165	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	59	theme	superior	1135:1142	arg1	concentrations					1113:1126	persistently elevated BSP concentrations	1087:1126	persistently elevated BSP concentrations	1087:1126	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	60	theme	elevated	1100:1107	arg1	predictor					1144:1152	a superior predictor	1133:1152	a superior predictor of mortality	1133:1165	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	8	60	theme	elevated	1100:1107	arg1	concentrations					1113:1126	persistently elevated BSP concentrations	1087:1126	persistently elevated BSP concentrations	1087:1126	In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score.
29950701	7	61	theme	most	892:895	arg1	patients					897:904	most patients	892:904	most patients	892:904	While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome.
29950701	3	62	theme	healthy	459:465	arg1	donors					473:478	36 healthy blood donors	456:478	36 healthy blood donors	456:478	BSP levels were compared to 36 healthy blood donors and correlated to clinical data.
29779369	3	0	theme	glycoprotein	720:731	arg1	standards					733:741	glycoprotein standards	720:741	glycoprotein standards	720:741	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	4	1	theme	mass-defect	948:958	arg1	tags					967:970	mass-defect DiPyrO tags	948:970	mass-defect DiPyrO tags	948:970	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	1	2	theme	amine-reactive	166:179	arg1	ornithine					234:242	dimethyl pyrimidinyl ornithine	213:242	dimethyl pyrimidinyl ornithine (DiPyrO)	213:251	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	2	theme	amine-reactive	166:179	arg1	tag					208:210	a novel amine-reactive mass-defect-based chemical tag	158:210	a novel amine-reactive mass-defect-based chemical tag	158:210	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	3	theme	proteomic	271:279	arg1	analysis					281:288	quantitative proteomic analysis	258:288	quantitative proteomic analysis at the MS1 level	258:305	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	2	4	theme	amine	390:394	arg1	reactivity					402:411	amine group reactivity	390:411	amine group reactivity	390:411	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	3	5	theme	released	689:696	arg1	N-glycosylamines					698:713	freshly released N-glycosylamines	681:713	freshly released N-glycosylamines	681:713	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	3	6	theme	glycosylamine	655:667	arg1	moieties					669:676	the glycosylamine moieties	651:676	the glycosylamine moieties of freshly released N-glycosylamines	651:713	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	1	7	theme	mass-defect-based	181:197	arg1	ornithine					234:242	dimethyl pyrimidinyl ornithine	213:242	dimethyl pyrimidinyl ornithine (DiPyrO)	213:251	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	7	theme	mass-defect-based	181:197	arg1	tag					208:210	a novel amine-reactive mass-defect-based chemical tag	158:210	a novel amine-reactive mass-defect-based chemical tag	158:210	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	0	8	theme	High-Resolution	101:115	arg1	Spectrometry					122:133	High-Resolution Mass Spectrometry	101:133	High-Resolution Mass Spectrometry	101:133	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	3	9	theme	N-glycosylamines	698:713	arg1	moieties					669:676	the glycosylamine moieties	651:676	the glycosylamine moieties of freshly released N-glycosylamines	651:713	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	7	10	theme	glycans	1431:1437	arg1	quantification					1413:1426	relative quantification	1404:1426	relative quantification of glycans	1404:1437	Moreover, this study also opens a door for using well-developed amine-reactive tags for relative quantification of glycans, which could be widely applied.
29779369	6	11	theme	serum	1237:1241	arg1	proteins					1243:1250	human serum proteins	1231:1250	human serum proteins of cancer patients before and after chemotherapy	1231:1299	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	3	12	theme	human	747:751	arg1	proteins					759:766	human serum proteins	747:766	human serum proteins	747:766	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	4	13	theme	charged	917:923	arg1	N-glycans					925:933	the singly or multiply charged N-glycans	894:933	the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags	894:970	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	6	14	theme	cancer	1255:1260	arg1	patients					1262:1269	cancer patients	1255:1269	cancer patients before and after chemotherapy	1255:1299	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	2	15	gly	glycoproteins	540:552	arg1	glycoproteins					540:552	glycoproteins	540:552	glycoproteins in the glycosylamine form	540:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	6	16	theme	MS	1164:1165	arg1	parameters					1179:1188	MS acquisition parameters	1164:1188	MS acquisition parameters	1164:1188	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	3	17	theme	serum	753:757	arg1	proteins					759:766	human serum proteins	747:766	human serum proteins	747:766	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	6	18	theme	glycosylamine	1125:1137	arg1	conditions					1148:1157	glycosylamine labeling conditions	1125:1157	glycosylamine labeling conditions	1125:1157	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	5	19	theme	peak	1019:1022	arg1	intensities					1024:1034	MS1 peak intensities	1015:1034	MS1 peak intensities	1015:1034	Dynamic range of quantification, based on MS1 peak intensities, was evaluated across 2 orders of magnitude.
29779369	6	20	from	abundances	1217:1226	arg1	proteins					1243:1250	human serum proteins	1231:1250	human serum proteins of cancer patients before and after chemotherapy	1231:1299	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	1	21	theme	chemical	199:206	arg1	ornithine					234:242	dimethyl pyrimidinyl ornithine	213:242	dimethyl pyrimidinyl ornithine (DiPyrO)	213:251	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	21	theme	chemical	199:206	arg1	tag					208:210	a novel amine-reactive mass-defect-based chemical tag	158:210	a novel amine-reactive mass-defect-based chemical tag	158:210	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	0	22	theme	Mass	117:120	arg1	Spectrometry					122:133	High-Resolution Mass Spectrometry	101:133	High-Resolution Mass Spectrometry	101:133	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	4	23	theme	MALDI-LTQ-Orbitrap	794:811	arg1	platforms					859:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	6	24	theme	labeling	1139:1146	arg1	conditions					1148:1157	glycosylamine labeling conditions	1125:1157	glycosylamine labeling conditions	1125:1157	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	0	25	theme	Glycomic	13:20	arg1	Analysis					22:29	Quantitative Glycomic Analysis	0:29	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.	0:134	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	3	26	theme	DiPyrO	588:593	arg1	tags					595:598	Duplex DiPyrO tags	581:598	Duplex DiPyrO tags that differ in mass by 45.3 mDa	581:630	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	0	27	theme	Quantitative	0:11	arg1	Analysis					22:29	Quantitative Glycomic Analysis	0:29	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.	0:134	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	1	28	theme	MS1	297:299	arg1	level					301:305	the MS1 level	293:305	the MS1 level	293:305	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	29	from	level	301:305	arg1	analysis					281:288	quantitative proteomic analysis	258:288	quantitative proteomic analysis at the MS1 level	258:305	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	6	30	theme	N-glycan	1096:1103	arg1	conditions					1113:1122	optimized N-glycan release conditions	1086:1122	optimized N-glycan release conditions	1086:1122	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	5	31	theme	quantification	990:1003	arg1	range					981:985	Dynamic range	973:985	Dynamic range	973:985	Dynamic range of quantification, based on MS1 peak intensities, was evaluated across 2 orders of magnitude.
29779369	1	32	theme	dimethyl	213:220	arg1	ornithine					234:242	dimethyl pyrimidinyl ornithine	213:242	dimethyl pyrimidinyl ornithine (DiPyrO)	213:251	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	32	theme	dimethyl	213:220	arg1	tag					208:210	a novel amine-reactive mass-defect-based chemical tag	158:210	a novel amine-reactive mass-defect-based chemical tag	158:210	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	32	theme	dimethyl	213:220	arg1	DiPyrO					245:250	DiPyrO	245:250	DiPyrO	245:250	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	3	33	used	used	637:640	arg2	tags					595:598	Duplex DiPyrO tags	581:598	Duplex DiPyrO tags that differ in mass by 45.3 mDa	581:630	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	6	34	theme	N-glycan	1195:1202	arg1	profiles					1204:1211	the N-glycan profiles	1191:1211	the N-glycan profiles	1191:1211	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	1	35	theme	pyrimidinyl	222:232	arg1	ornithine					234:242	dimethyl pyrimidinyl ornithine	213:242	dimethyl pyrimidinyl ornithine (DiPyrO)	213:251	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	35	theme	pyrimidinyl	222:232	arg1	tag					208:210	a novel amine-reactive mass-defect-based chemical tag	158:210	a novel amine-reactive mass-defect-based chemical tag	158:210	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	35	theme	pyrimidinyl	222:232	arg1	DiPyrO					245:250	DiPyrO	245:250	DiPyrO	245:250	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	2	36	theme	detection	422:430	arg1	capability					432:441	optical detection capability	414:441	optical detection capability	414:441	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	2	37	theme	glycosylamine	561:573	arg1	form					575:578	the glycosylamine form	557:578	the glycosylamine form	557:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	3	38	theme	Duplex	581:586	arg1	tags					595:598	Duplex DiPyrO tags	581:598	Duplex DiPyrO tags that differ in mass by 45.3 mDa	581:630	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	6	39	from	profiles	1204:1211	arg1	proteins					1243:1250	human serum proteins	1231:1250	human serum proteins of cancer patients before and after chemotherapy	1231:1299	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	6	40	theme	optimized	1086:1094	arg1	conditions					1113:1122	optimized N-glycan release conditions	1086:1122	optimized N-glycan release conditions	1086:1122	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	0	41	theme	Dimethyl	52:59	arg1	Tags					92:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	6	42	theme	release	1105:1111	arg1	conditions					1113:1122	optimized N-glycan release conditions	1086:1122	optimized N-glycan release conditions	1086:1122	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	0	43	theme	Mass-Defect-Based	34:50	arg1	Tags					92:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	3	44	gly	glycoprotein	720:731	arg1	glycoprotein					720:731	glycoprotein standards	720:741	glycoprotein standards	720:741	Duplex DiPyrO tags that differ in mass by 45.3 mDa were used to label the glycosylamine moieties of freshly released N-glycosylamines from glycoprotein standards and human serum proteins.
29779369	7	45	theme	amine-reactive	1380:1393	arg1	tags					1395:1398	well-developed amine-reactive tags	1365:1398	well-developed amine-reactive tags for relative quantification of glycans	1365:1437	Moreover, this study also opens a door for using well-developed amine-reactive tags for relative quantification of glycans, which could be widely applied.
29779369	4	46	theme	Orbitrap	850:857	arg1	platforms					859:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	2	47	theme	group	396:400	arg1	reactivity					402:411	amine group reactivity	390:411	amine group reactivity	390:411	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	0	48	theme	Ornithine	73:81	arg1	Tags					92:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	2	49	theme	N-linked	495:502	arg1	glycans					504:510	N-linked glycans	495:510	N-linked glycans enzymatically released from glycoproteins in the glycosylamine form	495:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	5	50	theme	MS1	1015:1017	arg1	intensities					1024:1034	MS1 peak intensities	1015:1034	MS1 peak intensities	1015:1034	Dynamic range of quantification, based on MS1 peak intensities, was evaluated across 2 orders of magnitude.
29779369	0	51	theme	Pyrimidinyl	61:71	arg1	Tags					92:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	6	52	theme	human	1231:1235	arg1	proteins					1243:1250	human serum proteins	1231:1250	human serum proteins of cancer patients before and after chemotherapy	1231:1299	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	7	53	theme	well-developed	1365:1378	arg1	tags					1395:1398	well-developed amine-reactive tags	1365:1398	well-developed amine-reactive tags for relative quantification of glycans	1365:1437	Moreover, this study also opens a door for using well-developed amine-reactive tags for relative quantification of glycans, which could be widely applied.
29779369	2	54	theme	improved	448:455	arg1	sensitivity					470:480	improved electrospray sensitivity	448:480	improved electrospray sensitivity	448:480	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	5	55	theme	magnitude	1070:1078	arg1	orders					1060:1065	2 orders	1058:1065	2 orders of magnitude	1058:1078	Dynamic range of quantification, based on MS1 peak intensities, was evaluated across 2 orders of magnitude.
29779369	7	56	theme	relative	1404:1411	arg1	quantification					1413:1426	relative quantification	1404:1426	relative quantification of glycans	1404:1437	Moreover, this study also opens a door for using well-developed amine-reactive tags for relative quantification of glycans, which could be widely applied.
29779369	4	57	theme	DiPyrO	960:965	arg1	tags					967:970	mass-defect DiPyrO tags	948:970	mass-defect DiPyrO tags	948:970	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	6	58	theme	patients	1262:1269	arg1	proteins					1243:1250	human serum proteins	1231:1250	human serum proteins of cancer patients before and after chemotherapy	1231:1299	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	4	59	theme	LC/MS/MS	828:835	arg1	platforms					859:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	2	60	link	N-linked	495:502	arg1	glycans					504:510	N-linked glycans	495:510	N-linked glycans enzymatically released from glycoproteins in the glycosylamine form	495:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	5	61	theme	Dynamic	973:979	arg1	range					981:985	Dynamic range	973:985	Dynamic range	973:985	Dynamic range of quantification, based on MS1 peak intensities, was evaluated across 2 orders of magnitude.
29779369	2	62	attach	released	526:533	arg2	glycans					504:510	N-linked glycans	495:510	N-linked glycans enzymatically released from glycoproteins in the glycosylamine form	495:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	2	62	attach	released	526:533	arg1	glycoproteins					540:552	glycoproteins	540:552	glycoproteins in the glycosylamine form	540:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	2	63	from	glycoproteins	540:552	arg1	form					575:578	the glycosylamine form	557:578	the glycosylamine form	557:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	4	64	theme	nano-HILIC	817:826	arg1	platforms					859:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	2	65	theme	DiPyrO	363:368	arg1	tag					370:372	the DiPyrO tag	359:372	the DiPyrO tag	359:372	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	6	66	theme	acquisition	1167:1177	arg1	parameters					1179:1188	MS acquisition parameters	1164:1188	MS acquisition parameters	1164:1188	With optimized N-glycan release conditions, glycosylamine labeling conditions, and MS acquisition parameters, the N-glycan profiles and abundances in human serum proteins of cancer patients before and after chemotherapy were compared.
29779369	0	67	theme	DiPyrO	84:89	arg1	Tags					92:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags	34:95	Quantitative Glycomic Analysis by Mass-Defect-Based Dimethyl Pyrimidinyl Ornithine (DiPyrO) Tags and High-Resolution Mass Spectrometry.
29779369	4	68	theme	Lumos	844:848	arg1	platforms					859:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	2	69	theme	optical	414:420	arg1	capability					432:441	optical detection capability	414:441	optical detection capability	414:441	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	2	70	theme	tag	370:372	arg1	application					344:354	the application	340:354	the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form	340:578	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	2	71	theme	electrospray	457:468	arg1	sensitivity					470:480	improved electrospray sensitivity	448:480	improved electrospray sensitivity	448:480	In this work, we further extend the application of the DiPyrO tag, which provides amine group reactivity, optical detection capability, and improved electrospray sensitivity, to quantify N-linked glycans enzymatically released from glycoproteins in the glycosylamine form.
29779369	4	72	theme	Fusion	837:842	arg1	platforms					859:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms	789:867	We demonstrate that both MALDI-LTQ-Orbitrap and nano-HILIC LC/MS/MS Fusion Lumos Orbitrap platforms are capable of resolving the singly or multiply charged N-glycans labeled with mass-defect DiPyrO tags.
29779369	1	73	theme	novel	160:164	arg1	ornithine					234:242	dimethyl pyrimidinyl ornithine	213:242	dimethyl pyrimidinyl ornithine (DiPyrO)	213:251	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	73	theme	novel	160:164	arg1	tag					208:210	a novel amine-reactive mass-defect-based chemical tag	158:210	a novel amine-reactive mass-defect-based chemical tag	158:210	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29779369	1	74	theme	quantitative	258:269	arg1	analysis					281:288	quantitative proteomic analysis	258:288	quantitative proteomic analysis at the MS1 level	258:305	We recently developed a novel amine-reactive mass-defect-based chemical tag, dimethyl pyrimidinyl ornithine (DiPyrO), for quantitative proteomic analysis at the MS1 level.
29409894	7	0	theme	mns1	1230:1233	arg1	roots					1240:1244	mns1 mns2 roots	1230:1244	mns1 mns2 roots under high salinity	1230:1264	Interestingly, we observed that cellulose biosynthesis was compromised in mns1 mns2 roots under high salinity.
29409894	4	1	theme	A	713:713	arg1	branches					721:728	the A and C branches	709:728	the A and C branches of plant N-glycans	709:747	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	8	2	dep	anchored	1305:1312	arg1	membrane					1296:1303	membrane	1296:1303	membrane	1296:1303	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	7	3	theme	mns2	1235:1238	arg1	roots					1240:1244	mns1 mns2 roots	1230:1244	mns1 mns2 roots under high salinity	1230:1264	Interestingly, we observed that cellulose biosynthesis was compromised in mns1 mns2 roots under high salinity.
29409894	10	4	theme	salt	1727:1730	arg1	stress					1732:1737	salt stress	1727:1737	salt stress in plants	1727:1747	Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
29409894	4	5	from	inhibition	776:785	arg1	Arabidopsis					819:829	Arabidopsis	819:829	Arabidopsis	819:829	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	3	6	theme	Golgi-mediated	520:533	arg1	trimming					543:550	Golgi-mediated mannose trimming	520:550	Golgi-mediated mannose trimming	520:550	However, the biological importance of Golgi-mediated mannose trimming is not fully understood.
29409894	6	7	from	mutation	998:1005	arg1	EBS3					1010:1013	EBS3	1010:1013	EBS3	1010:1013	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	2	8	from	N-glycans	458:466	arg1	Golgi					475:479	the Golgi	471:479	the Golgi	471:479	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	3	9	theme	mannose	535:541	arg1	trimming					543:550	Golgi-mediated mannose trimming	520:550	Golgi-mediated mannose trimming	520:550	However, the biological importance of Golgi-mediated mannose trimming is not fully understood.
29409894	4	10	theme	root	764:767	arg1	inhibition					776:785	severe root growth inhibition	757:785	severe root growth inhibition under salt stress conditions in Arabidopsis	757:829	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	4	11	from	trimming	697:704	arg1	branches					721:728	the A and C branches	709:728	the A and C branches of plant N-glycans	709:747	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	0	12	from	Stress	142:147	arg1	Arabidopsis					152:162	Arabidopsis	152:162	Arabidopsis	152:162	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	10	13	theme	N-glycans	1656:1664	arg1	trimming					1644:1651	MNS1/2-mediated mannose trimming	1620:1651	MNS1/2-mediated mannose trimming of N-glycans	1620:1664	Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
29409894	1	14	link	-linked	183:189	arg1	glycans					191:197	Asparagine (Asn/N)-linked glycans	165:197	Asparagine (Asn/N)-linked glycans	165:197	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	4	15	theme	severe	757:762	arg1	inhibition					776:785	severe root growth inhibition	757:785	severe root growth inhibition under salt stress conditions in Arabidopsis	757:829	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	8	16	theme	endo-β-1,4-endoglucanase	1314:1337	arg1	 abundance					1280:1289	 abundance	1280:1289	 abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were	1280:1431	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	4	17	theme	C	719:719	arg1	branches					721:728	the A and C branches	709:728	the A and C branches of plant N-glycans	709:747	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	1	18	from	degradation	284:294	arg1	eukaryotes					299:308	eukaryotes	299:308	eukaryotes	299:308	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	2	19	theme	sugar	424:428	arg1	molecules					430:438	other sugar molecules	418:438	other sugar molecules	418:438	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	6	20	theme	branched	1059:1066	arg1	precursor					1077:1085	the branched N-glycan precursor	1055:1085	the branched N-glycan precursor	1055:1085	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	4	21	theme	responsible	667:677	arg1	MNS2					661:664	MNS2	661:664	MNS2	661:664	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	4	21	theme	responsible	667:677	arg1	MNS1					652:655	MNS1	652:655	MNS1	652:655	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	4	21	theme	responsible	667:677	arg1	mannosidases					638:649	two functionally redundant mannosidases	611:649	two functionally redundant mannosidases	611:649	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	9	22	theme	RSW2	1506:1509	arg1	Overexpression					1488:1501	Overexpression	1488:1501	Overexpression of RSW2	1488:1509	Overexpression of RSW2 could partially rescue the salt-sensitive phenotype of mns1 mns2.
29409894	8	23	theme	cellulose	1375:1383	arg1	biosynthesis					1385:1396	cellulose biosynthesis	1375:1396	cellulose biosynthesis	1375:1396	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	10	24	theme	glycoprotein	1691:1702	arg1	abundance					1704:1712	glycoprotein abundance	1691:1712	glycoprotein abundance	1691:1712	Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
29409894	4	25	theme	growth	769:774	arg1	inhibition					776:785	severe root growth inhibition	757:785	severe root growth inhibition under salt stress conditions in Arabidopsis	757:829	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	6	26	theme	N-glycan	1068:1075	arg1	precursor					1077:1085	the branched N-glycan precursor	1055:1085	the branched N-glycan precursor	1055:1085	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	8	27	theme	by α-1,2-mannose	1443:1458	arg1	trimming					1460:1467	by α-1,2-mannose trimming	1443:1467	by α-1,2-mannose trimming	1443:1467	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	10	28	theme	MNS1/2-mediated	1620:1634	arg1	trimming					1644:1651	MNS1/2-mediated mannose trimming	1620:1651	MNS1/2-mediated mannose trimming of N-glycans	1620:1664	Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
29409894	4	29	theme	N-glycans	739:747	arg1	branches					721:728	the A and C branches	709:728	the A and C branches of plant N-glycans	709:747	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	0	30	theme	Salt	137:140	arg1	Stress					142:147	Salt Stress	137:147	Salt Stress in Arabidopsis	137:162	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	4	31	theme	α-1,2-mannose	683:695	arg1	trimming					697:704	α-1,2-mannose trimming	683:704	α-1,2-mannose trimming on the A and C branches of plant N-glycans	683:747	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	7	32	theme	that cellulose	1183:1196	arg1	biosynthesis					1198:1209	that cellulose biosynthesis	1183:1209	that cellulose biosynthesis	1183:1209	Interestingly, we observed that cellulose biosynthesis was compromised in mns1 mns2 roots under high salinity.
29409894	1	33	theme	endoplasmic	251:261	arg1	degradation					284:294	endoplasmic reticulum-associated degradation	251:294	endoplasmic reticulum-associated degradation in eukaryotes	251:308	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	10	34	gly	glycoprotein	1691:1702	arg1	glycoprotein					1691:1702	glycoprotein abundance	1691:1712	glycoprotein abundance	1691:1712	Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
29409894	4	35	theme	plant	733:737	arg1	N-glycans					739:747	plant N-glycans	733:747	plant N-glycans	733:747	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	9	36	theme	mns2	1571:1574	arg1	phenotype					1553:1561	the salt-sensitive phenotype	1534:1561	the salt-sensitive phenotype of mns1 mns2	1534:1574	Overexpression of RSW2 could partially rescue the salt-sensitive phenotype of mns1 mns2.
29409894	2	37	theme	three-branched	443:456	arg1	N-glycans					458:466	three-branched N-glycans	443:466	three-branched N-glycans in the Golgi	443:479	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	1	38	theme	reticulum-associated	263:282	arg1	degradation					284:294	endoplasmic reticulum-associated degradation	251:294	endoplasmic reticulum-associated degradation in eukaryotes	251:308	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	0	39	theme	Protein	112:118	arg1	Abundance					120:128	RSW2 Protein Abundance	107:128	RSW2 Protein Abundance	107:128	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	5	40	theme	oligosaccharide	893:907	arg1	precursor					909:917	the oligosaccharide precursor	889:917	the oligosaccharide precursor	889:917	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	6	41	theme	mutant	1148:1153	arg1	phenotype					1118:1126	the salt-sensitive phenotype	1099:1126	the salt-sensitive phenotype of mns1 mns2 double mutant	1099:1153	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	2	42	theme	molecules	430:438	arg1	addition					406:413	addition	406:413	addition of other sugar molecules to three-branched N-glycans in the Golgi	406:479	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	2	42	theme	molecules	430:438	arg1	mannosidases					389:400	mannosidases	389:400	mannosidases	389:400	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	0	43	theme	N-Glycans	12:20	arg1	Trimming					0:7	Trimming	0:7	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2,	0:78	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	0	44	theme	RSW2	107:110	arg1	Abundance					120:128	RSW2 Protein Abundance	107:128	RSW2 Protein Abundance	107:128	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	5	45	theme	precursor	909:917	arg1	biosynthesis					873:884	the biosynthesis	869:884	the biosynthesis of the oligosaccharide precursor	869:917	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	1	46	theme	-linked	183:189	arg1	glycans					191:197	Asparagine (Asn/N)-linked glycans	165:197	Asparagine (Asn/N)-linked glycans	165:197	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	0	47	theme	Golgi-Localized	29:43	arg1	MNS2					74:77	MNS2	74:77	MNS2	74:77	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	0	47	theme	Golgi-Localized	29:43	arg1	MNS1					65:68	MNS1	65:68	MNS1	65:68	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	0	47	theme	Golgi-Localized	29:43	arg1	α-1,2-Mannosidases					45:62	the Golgi-Localized α-1,2-Mannosidases	25:62	the Golgi-Localized α-1,2-Mannosidases	25:62	Trimming of N-Glycans by the Golgi-Localized α-1,2-Mannosidases, MNS1 and MNS2, Is Crucial for Maintaining RSW2 Protein Abundance during Salt Stress in Arabidopsis.
29409894	5	48	theme	mannose	971:977	arg1	trimming					979:986	mannose trimming	971:986	mannose trimming	971:986	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	9	49	theme	salt-sensitive	1538:1551	arg1	phenotype					1553:1561	the salt-sensitive phenotype	1534:1561	the salt-sensitive phenotype of mns1 mns2	1534:1574	Overexpression of RSW2 could partially rescue the salt-sensitive phenotype of mns1 mns2.
29409894	6	50	theme	mns1	1131:1134	arg1	mutant					1148:1153	mns1 mns2 double mutant	1131:1153	mns1 mns2 double mutant	1131:1153	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	8	51	theme	variant	1413:1419	arg1	rsw2-1 were					1421:1431	its mutant variant rsw2-1 were	1402:1431	its mutant variant rsw2-1 were	1402:1431	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	2	52	theme	other	418:422	arg1	molecules					430:438	other sugar molecules	418:438	other sugar molecules	418:438	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	6	53	theme	precursor	1077:1085	arg1	formation					1042:1050	the formation	1038:1050	the formation of the branched N-glycan precursor	1038:1085	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	1	54	from	trafficking	234:244	arg1	eukaryotes					299:308	eukaryotes	299:308	eukaryotes	299:308	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	4	55	theme	mannosidases	638:649	arg1	abolishment					596:606	abolishment	596:606	abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans	596:747	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	8	56	theme	anchored	1305:1312	arg1	endo-β-1,4-endoglucanase					1314:1337	a membrane anchored endo-β-1,4-endoglucanase	1294:1337	a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were	1294:1431	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	8	56	theme	anchored	1305:1312	arg1	RSW2/KOR					1340:1347	RSW2/KOR	1340:1347	RSW2/KOR	1340:1347	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	10	57	theme	mannose	1636:1642	arg1	trimming					1644:1651	MNS1/2-mediated mannose trimming	1620:1651	MNS1/2-mediated mannose trimming of N-glycans	1620:1664	Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
29409894	8	58	theme	key	1363:1365	arg1	role					1367:1370	a key role	1361:1370	a key role	1361:1370	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	10	59	from	stress	1732:1737	arg1	plants					1742:1747	plants	1742:1747	plants	1742:1747	Taken together, these results suggest that MNS1/2-mediated mannose trimming of N-glycans is crucial in modulating glycoprotein abundance to withstand salt stress in plants.
29409894	5	60	theme	trimming	979:986	arg1	absence					960:966	the absence	956:966	the absence of mannose trimming	956:986	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	6	61	theme	salt-sensitive	1103:1116	arg1	phenotype					1118:1126	the salt-sensitive phenotype	1099:1126	the salt-sensitive phenotype of mns1 mns2 double mutant	1099:1153	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	3	62	theme	biological	495:504	arg1	importance					506:515	the biological importance	491:515	the biological importance of Golgi-mediated mannose trimming	491:550	However, the biological importance of Golgi-mediated mannose trimming is not fully understood.
29409894	1	63	from	folding	225:231	arg1	eukaryotes					299:308	eukaryotes	299:308	eukaryotes	299:308	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	5	64	theme	enhanced	929:936	arg1	tolerance					943:951	enhanced salt tolerance	929:951	enhanced salt tolerance	929:951	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	4	65	theme	salt	793:796	arg1	conditions					805:814	salt stress conditions	793:814	salt stress conditions	793:814	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	8	66	theme	mutant	1406:1411	arg1	rsw2-1 were					1421:1431	its mutant variant rsw2-1 were	1402:1431	its mutant variant rsw2-1 were	1402:1431	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	2	67	theme	glycoproteins	329:341	arg1	maturation					315:324	The maturation	311:324	The maturation of glycoproteins	311:341	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	2	68	gly	glycoproteins	329:341	arg1	glycoproteins					329:341	glycoproteins	329:341	glycoproteins	329:341	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	4	69	dep	A	713:713	arg1	the					709:711	the	709:711	the	709:711	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	3	70	theme	trimming	543:550	arg1	importance					506:515	the biological importance	491:515	the biological importance of Golgi-mediated mannose trimming	491:550	However, the biological importance of Golgi-mediated mannose trimming is not fully understood.
29409894	6	71	theme	mns2	1136:1139	arg1	mutant					1148:1153	mns1 mns2 double mutant	1131:1153	mns1 mns2 double mutant	1131:1153	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	5	72	theme	salt	938:941	arg1	tolerance					943:951	enhanced salt tolerance	929:951	enhanced salt tolerance	929:951	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	8	73	theme	salt	1475:1478	arg1	stress					1480:1485	salt stress	1475:1485	salt stress	1475:1485	Consistently, abundance of a membrane anchored endo-β-1,4-endoglucanase (RSW2/KOR) that plays a key role in cellulose biosynthesis and its mutant variant rsw2-1 were modulated by α-1,2-mannose trimming under salt stress.
29409894	9	74	theme	mns1	1566:1569	arg1	mns2					1571:1574	mns1 mns2	1566:1574	mns1 mns2	1566:1574	Overexpression of RSW2 could partially rescue the salt-sensitive phenotype of mns1 mns2.
29409894	2	75	theme	residues	377:384	arg1	trimming					356:363	the trimming	352:363	the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi	352:479	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	5	76	with	mutants	845:851	arg1	defects					858:864	defects	858:864	defects in the biosynthesis of the oligosaccharide precursor	858:917	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	1	77	theme	protein	217:223	arg1	folding					225:231	protein folding	217:231	protein folding	217:231	Asparagine (Asn/N)-linked glycans are important for protein folding, trafficking, and endoplasmic reticulum-associated degradation in eukaryotes.
29409894	6	78	theme	double	1141:1146	arg1	mutant					1148:1153	mns1 mns2 double mutant	1131:1153	mns1 mns2 double mutant	1131:1153	However, mutation in EBS3, which is required for the formation of the branched N-glycan precursor, suppressed the salt-sensitive phenotype of mns1 mns2 double mutant.
29409894	4	79	theme	stress	798:803	arg1	conditions					805:814	salt stress conditions	793:814	salt stress conditions	793:814	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	5	80	from	defects	858:864	arg1	biosynthesis					873:884	the biosynthesis	869:884	the biosynthesis of the oligosaccharide precursor	869:917	In contrast, mutants with defects in the biosynthesis of the oligosaccharide precursor displayed enhanced salt tolerance in the absence of mannose trimming.
29409894	2	81	theme	mannosyl	368:375	arg1	residues					377:384	mannosyl residues	368:384	mannosyl residues	368:384	The maturation of glycoproteins involves the trimming of mannosyl residues by mannosidases and addition of other sugar molecules to three-branched N-glycans in the Golgi.
29409894	7	82	theme	high	1252:1255	arg1	salinity					1257:1264	high salinity	1252:1264	high salinity	1252:1264	Interestingly, we observed that cellulose biosynthesis was compromised in mns1 mns2 roots under high salinity.
29409894	4	83	theme	redundant	628:636	arg1	MNS2					661:664	MNS2	661:664	MNS2	661:664	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	4	83	theme	redundant	628:636	arg1	MNS1					652:655	MNS1	652:655	MNS1	652:655	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
29409894	4	83	theme	redundant	628:636	arg1	mannosidases					638:649	two functionally redundant mannosidases	611:649	two functionally redundant mannosidases	611:649	Here, we show that abolishment of two functionally redundant mannosidases, MNS1 and MNS2, responsible for α-1,2-mannose trimming on the A and C branches of plant N-glycans lead to severe root growth inhibition under salt stress conditions in Arabidopsis.
28057501	7	0	theme	carboxylase	1275:1285	arg1	higher					1351:1356	higher	1351:1356	higher	1351:1356	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	0	theme	carboxylase	1275:1285	arg1	activity					1287:1294	the specific pyruvate carboxylase activity	1253:1294	the specific pyruvate carboxylase activity in MA production medium supplemented with CSL	1253:1340	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	1	theme	malic	1571:1575	arg1	acid					1577:1580	malic acid	1571:1580	malic acid in P. viticola 152 strain	1571:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	1	2	from	marine	217:222	arg1	PYC					205:207	PYC	205:207	PYC	205:207	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	1	2	from	marine	217:222	arg1	gene					199:202	a pyruvate carboxylase gene	176:202	a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae	176:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	3	3	from	-666bp	598:603	arg1	located					587:593	located	587:593	located	587:593	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	3	from	-666bp	598:603	arg1	promoter					549:556	A putative promoter	538:556	A putative promoter (intronless) of the gene	538:581	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	7	4	theme	specific	1257:1264	arg1	higher					1351:1356	higher	1351:1356	higher	1351:1356	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	4	theme	specific	1257:1264	arg1	activity					1287:1294	the specific pyruvate carboxylase activity	1253:1294	the specific pyruvate carboxylase activity in MA production medium supplemented with CSL	1253:1340	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	5	theme	131.2757kDa	525:535	arg1	weight					515:520	a calculated molecular weight	492:520	a calculated molecular weight of 131.2757kDa	492:535	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	7	6	from	expression	1145:1154	arg1	medium					1194:1199	medium	1194:1199	medium supplemented with CSL and biotin	1194:1232	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	3	7	theme	several	631:637	arg1	boxes					644:648	several CAAT boxes	631:648	several CAAT boxes	631:648	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	7	theme	several	631:637	arg1	box					626:628	a TATA box	619:628	a TATA box	619:628	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	7	8	theme	high	1546:1549	arg1	production					1557:1566	high level production	1546:1566	high level production of malic acid in P. viticola 152 strain	1546:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	6	9	gly	N-glycosylation	1116:1130	arg2	-N-S-T-I-					1004:1012	-N-S-T-I-	1004:1012	-N-S-T-I- at 36 amino acid	1004:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	9	gly	N-glycosylation	1116:1130	arg2	-N-G-T-V-					1032:1040	-N-G-T-V-	1032:1040	-N-G-T-V- at 237 amino acid	1032:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	9	gly	N-glycosylation	1116:1130	arg2	sites					1132:1136	the most possible N-glycosylation sites	1098:1136	the most possible N-glycosylation sites	1098:1136	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	9	gly	N-glycosylation	1116:1130	arg2	-N-G-S-S-					1065:1073	-N-G-S-S-	1065:1073	-N-G-S-S- at 517 amino acid	1065:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	2	10	contain	had	417:419	arg2	3582bp					421:426	3582bp	421:426	3582bp encoding 1193 amino acid protein (isoelectric point: 5.01)	421:485	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	2	10	contain	had	417:419	arg1	ORF					367:369	ORF	367:369	ORF	367:369	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	2	10	contain	had	417:419	arg1	frame					360:364	An open reading frame	344:364	An open reading frame (ORF) of The PYC gene (accession number: KM593097)	344:415	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	1	11	theme	carboxylase	187:197	arg1	PYC					205:207	PYC	205:207	PYC	205:207	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	1	11	theme	carboxylase	187:197	arg1	gene					199:202	a pyruvate carboxylase gene	176:202	a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae	176:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	7	12	from	production	1557:1566	arg1	strain					1601:1606	P. viticola 152 strain	1585:1606	P. viticola 152 strain	1585:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	13	theme	viticola	1178:1185	arg1	expression					1145:1154	expression	1145:1154	expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin	1145:1232	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	0	14	theme	expression	140:149	arg1	analysis					151:158	its expression analysis	136:158	its expression analysis	136:158	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	6	15	theme	possible	1107:1114	arg1	-N-G-S-S-					1065:1073	-N-G-S-S-	1065:1073	-N-G-S-S- at 517 amino acid	1065:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	15	theme	possible	1107:1114	arg1	-N-S-T-I-					1004:1012	-N-S-T-I-	1004:1012	-N-S-T-I- at 36 amino acid	1004:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	15	theme	possible	1107:1114	arg1	-N-G-T-V-					1032:1040	-N-G-T-V-	1032:1040	-N-G-T-V- at 237 amino acid	1032:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	15	theme	possible	1107:1114	arg1	sites					1132:1136	the most possible N-glycosylation sites	1098:1136	the most possible N-glycosylation sites	1098:1136	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	7	16	theme	PYC	1511:1513	arg1	responsible					1530:1540	responsible	1530:1540	responsible	1530:1540	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	16	theme	PYC	1511:1513	arg1	gene					1515:1518	the PYC gene	1507:1518	the PYC gene	1507:1518	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	17	theme	calculated	494:503	arg1	weight					515:520	a calculated molecular weight	492:520	a calculated molecular weight of 131.2757kDa	492:535	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	7	18	theme	PYC	1163:1165	arg1	gene					1167:1170	the PYC gene	1159:1170	the PYC gene	1159:1170	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	19	dep	higher	1351:1356	arg1	0.5U/mg					1359:1365	0.5U/mg	1359:1365	0.5U/mg	1359:1365	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	20	theme	acid	448:451	arg1	protein					453:459	1193 amino acid protein	437:459	1193 amino acid protein (isoelectric point: 5.01)	437:485	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	6	21	contain	had	942:944	arg2	sites					985:989	three potential N-linked glycosylation sites	946:989	three potential N-linked glycosylation sites	946:989	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	21	contain	had	942:944	arg1	protein					929:935	PYC protein	925:935	PYC protein	925:935	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	3	22	contain	contained	609:617	arg2	boxes					644:648	several CAAT boxes	631:648	several CAAT boxes	631:648	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	22	contain	contained	609:617	arg2	box					626:628	a TATA box	619:628	a TATA box	619:628	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	22	contain	contained	609:617	arg2	sequences					687:695	the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences	651:695	the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences	651:695	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	22	contain	contained	609:617	arg1	promoter					549:556	A putative promoter	538:556	A putative promoter (intronless) of the gene	538:581	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	22	contain	contained	609:617	arg1	intronless					559:568	intronless	559:568	intronless	559:568	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	22	contain	contained	609:617	arg1	located					587:593	located	587:593	located	587:593	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	7	23	from	medium	1194:1199	arg1	expression					1145:1154	expression	1145:1154	expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin	1145:1232	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	24	theme	increased	1483:1491	arg1	expression					1493:1502	increased expression	1483:1502	increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain	1483:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	25	theme	1193	437:440	arg1	protein					453:459	1193 amino acid protein	437:459	1193 amino acid protein (isoelectric point: 5.01)	437:485	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	0	26	theme	malate	82:87	arg1	overproduction					89:102	calcium malate overproduction	74:102	calcium malate overproduction in Penicillium viticola 152	74:130	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	1	27	theme	Walking	328:334	arg1	method					336:341	Genome Walking method	321:341	Genome Walking method	321:341	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	5	28	theme	signal	835:840	arg1	peptide					842:848	no signal peptide	832:848	no signal peptide	832:848	The protein deduced from the PYC gene had no signal peptide, was a homotetramer (4), and had the four functional domains.
28057501	7	29	theme	CSL	1463:1465	arg1	concentration					1446:1458	optimal concentration	1438:1458	optimal concentration of CSL	1438:1465	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	30	dep	number	399:404	arg1	KM593097					407:414	KM593097	407:414	KM593097	407:414	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	5	31	theme	PYC	819:821	arg1	gene					823:826	the PYC gene	815:826	the PYC gene	815:826	The protein deduced from the PYC gene had no signal peptide, was a homotetramer (4), and had the four functional domains.
28057501	2	32	theme	accession	389:397	arg1	number					399:404	accession number	389:404	accession number: KM593097	389:414	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	1	33	attach	isolated	256:263	arg1	algae					277:281	marine algae	270:281	marine algae	270:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	1	33	attach	isolated	256:263	arg2	marine					217:222	a marine fungus Penicillium viticola 152	215:254	a marine fungus Penicillium viticola 152 isolated from marine algae	215:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	2	34	theme	gene	383:386	arg1	ORF					367:369	ORF	367:369	ORF	367:369	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	2	34	theme	gene	383:386	arg1	frame					360:364	An open reading frame	344:364	An open reading frame (ORF) of The PYC gene (accession number: KM593097)	344:415	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	2	35	dep	protein	453:459	arg1	point					474:478	isoelectric point	462:478	isoelectric point: 5.01	462:484	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	3	36	theme	gene	578:581	arg1	promoter					549:556	A putative promoter	538:556	A putative promoter (intronless) of the gene	538:581	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	36	theme	gene	578:581	arg1	located					587:593	located	587:593	located	587:593	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	36	theme	gene	578:581	arg1	intronless					559:568	intronless	559:568	intronless	559:568	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	4	37	theme	polyadenylation	710:724	arg1	AATAAA					732:737	AATAAA	732:737	AATAAA	732:737	A consensus polyadenylation site (AATAAA) was also observed at +10bp downstream of the ORF.
28057501	4	37	theme	polyadenylation	710:724	arg1	site					726:729	A consensus polyadenylation site	698:729	A consensus polyadenylation site (AATAAA)	698:738	A consensus polyadenylation site (AATAAA) was also observed at +10bp downstream of the ORF.
28057501	0	38	theme	pyruvate	32:39	arg1	gene					53:56	pyruvate carboxylase gene	32:56	pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152	32:130	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	7	39	from	strain	1601:1606	arg1	production					1557:1566	high level production	1546:1566	high level production of malic acid in P. viticola 152 strain	1546:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	6	40	link	N-linked	962:969	arg1	sites					985:989	three potential N-linked glycosylation sites	946:989	three potential N-linked glycosylation sites	946:989	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	0	41	theme	gene	53:56	arg1	characterization					12:27	characterization	12:27	characterization	12:27	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	0	41	theme	gene	53:56	arg1	Cloning					0:6	Cloning	0:6	Cloning	0:6	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	0	41	theme	gene	53:56	arg1	analysis					151:158	its expression analysis	136:158	its expression analysis	136:158	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	7	42	theme	MA	1299:1300	arg1	medium					1313:1318	MA production medium	1299:1318	MA production medium supplemented with CSL	1299:1340	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	6	43	theme	N-linked	962:969	arg1	sites					985:989	three potential N-linked glycosylation sites	946:989	three potential N-linked glycosylation sites	946:989	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	4	44	located	observed	749:756	arg2	AATAAA					732:737	AATAAA	732:737	AATAAA	732:737	A consensus polyadenylation site (AATAAA) was also observed at +10bp downstream of the ORF.
28057501	4	44	located	observed	749:756	arg2	site					726:729	A consensus polyadenylation site	698:729	A consensus polyadenylation site (AATAAA)	698:738	A consensus polyadenylation site (AATAAA) was also observed at +10bp downstream of the ORF.
28057501	4	44	located	observed	749:756	arg1	+10bp					761:765	+10bp	761:765	+10bp	761:765	A consensus polyadenylation site (AATAAA) was also observed at +10bp downstream of the ORF.
28057501	7	45	theme	acid	1577:1580	arg1	production					1557:1566	high level production	1546:1566	high level production of malic acid in P. viticola 152 strain	1546:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	46	theme	reading	352:358	arg1	ORF					367:369	ORF	367:369	ORF	367:369	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	2	46	theme	reading	352:358	arg1	frame					360:364	An open reading frame	344:364	An open reading frame (ORF) of The PYC gene (accession number: KM593097)	344:415	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	7	47	theme	pyruvate	1266:1273	arg1	higher					1351:1356	higher	1351:1356	higher	1351:1356	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	47	theme	pyruvate	1266:1273	arg1	activity					1287:1294	the specific pyruvate carboxylase activity	1253:1294	the specific pyruvate carboxylase activity in MA production medium supplemented with CSL	1253:1340	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	3	48	theme	TATA	621:624	arg1	boxes					644:648	several CAAT boxes	631:648	several CAAT boxes	631:648	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	48	theme	TATA	621:624	arg1	sequences					687:695	the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences	651:695	the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences	651:695	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	48	theme	TATA	621:624	arg1	box					626:628	a TATA box	619:628	a TATA box	619:628	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	1	49	theme	Penicillium	231:241	arg1	viticola					243:250	fungus Penicillium viticola 152	224:254	a marine fungus Penicillium viticola 152 isolated from marine algae	215:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	7	50	theme	level	1551:1555	arg1	production					1557:1566	high level production	1546:1566	high level production of malic acid in P. viticola 152 strain	1546:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	6	51	theme	PYC	925:927	arg1	protein					929:935	PYC protein	925:935	PYC protein	925:935	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	52	theme	amino	1082:1086	arg1	acid					1088:1091	517 amino acid	1078:1091	517 amino acid	1078:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	3	53	theme	CAAT	639:642	arg1	boxes					644:648	several CAAT boxes	631:648	several CAAT boxes	631:648	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	53	theme	CAAT	639:642	arg1	box					626:628	a TATA box	619:628	a TATA box	619:628	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	1	54	theme	pyruvate	178:185	arg1	PYC					205:207	PYC	205:207	PYC	205:207	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	1	54	theme	pyruvate	178:185	arg1	gene					199:202	a pyruvate carboxylase gene	176:202	a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae	176:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	5	55	contain	had	828:830	arg1	protein					794:800	The protein	790:800	The protein deduced from the PYC gene	790:826	The protein deduced from the PYC gene had no signal peptide, was a homotetramer (4), and had the four functional domains.
28057501	5	55	contain	had	828:830	arg2	peptide					842:848	no signal peptide	832:848	no signal peptide	832:848	The protein deduced from the PYC gene had no signal peptide, was a homotetramer (4), and had the four functional domains.
28057501	1	56	dep	marine	217:222	arg1	viticola					243:250	fungus Penicillium viticola 152	224:254	a marine fungus Penicillium viticola 152 isolated from marine algae	215:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	6	57	theme	amino	1049:1053	arg1	acid					1055:1058	237 amino acid	1045:1058	237 amino acid	1045:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	58	theme	N-glycosylation	1116:1130	arg1	-N-G-S-S-					1065:1073	-N-G-S-S-	1065:1073	-N-G-S-S- at 517 amino acid	1065:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	58	theme	N-glycosylation	1116:1130	arg1	-N-S-T-I-					1004:1012	-N-S-T-I-	1004:1012	-N-S-T-I- at 36 amino acid	1004:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	58	theme	N-glycosylation	1116:1130	arg1	-N-G-T-V-					1032:1040	-N-G-T-V-	1032:1040	-N-G-T-V- at 237 amino acid	1032:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	58	theme	N-glycosylation	1116:1130	arg1	sites					1132:1136	the most possible N-glycosylation sites	1098:1136	the most possible N-glycosylation sites	1098:1136	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	7	59	theme	MA	1376:1377	arg1	medium					1379:1384	MA medium	1376:1384	MA medium supplemented with biotin (0.3U/mg)	1376:1419	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	60	theme	molecular	505:513	arg1	weight					515:520	a calculated molecular weight	492:520	a calculated molecular weight of 131.2757kDa	492:535	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	6	61	theme	most	1102:1105	arg1	-N-G-S-S-					1065:1073	-N-G-S-S-	1065:1073	-N-G-S-S- at 517 amino acid	1065:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	61	theme	most	1102:1105	arg1	-N-S-T-I-					1004:1012	-N-S-T-I-	1004:1012	-N-S-T-I- at 36 amino acid	1004:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	61	theme	most	1102:1105	arg1	-N-G-T-V-					1032:1040	-N-G-T-V-	1032:1040	-N-G-T-V- at 237 amino acid	1032:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	61	theme	most	1102:1105	arg1	sites					1132:1136	the most possible N-glycosylation sites	1098:1136	the most possible N-glycosylation sites	1098:1136	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	7	62	theme	gene	1515:1518	arg1	expression					1493:1502	increased expression	1483:1502	increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain	1483:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	63	theme	gene	1167:1170	arg1	expression					1145:1154	expression	1145:1154	expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin	1145:1232	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	6	64	from	acid	1055:1058	arg1	-N-G-S-S-					1065:1073	-N-G-S-S-	1065:1073	-N-G-S-S- at 517 amino acid	1065:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	64	from	acid	1055:1058	arg1	-N-S-T-I-					1004:1012	-N-S-T-I-	1004:1012	-N-S-T-I- at 36 amino acid	1004:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	64	from	acid	1055:1058	arg1	-N-G-T-V-					1032:1040	-N-G-T-V-	1032:1040	-N-G-T-V- at 237 amino acid	1032:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	64	from	acid	1055:1058	arg1	sites					1132:1136	the most possible N-glycosylation sites	1098:1136	the most possible N-glycosylation sites	1098:1136	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	0	65	theme	calcium	74:80	arg1	overproduction					89:102	calcium malate overproduction	74:102	calcium malate overproduction in Penicillium viticola 152	74:130	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	5	66	theme	functional	892:901	arg1	domains					903:909	the four functional domains	883:909	the four functional domains	883:909	The protein deduced from the PYC gene had no signal peptide, was a homotetramer (4), and had the four functional domains.
28057501	3	67	theme	putative	540:547	arg1	promoter					549:556	A putative promoter	538:556	A putative promoter (intronless) of the gene	538:581	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	67	theme	putative	540:547	arg1	located					587:593	located	587:593	located	587:593	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	67	theme	putative	540:547	arg1	intronless					559:568	intronless	559:568	intronless	559:568	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	2	68	theme	amino	442:446	arg1	protein					453:459	1193 amino acid protein	437:459	1193 amino acid protein (isoelectric point: 5.01)	437:485	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	6	69	theme	amino	1020:1024	arg1	acid					1026:1029	36 amino acid	1017:1029	36 amino acid	1017:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	70	from	acid	1026:1029	arg1	-N-G-S-S-					1065:1073	-N-G-S-S-	1065:1073	-N-G-S-S- at 517 amino acid	1065:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	70	from	acid	1026:1029	arg1	-N-S-T-I-					1004:1012	-N-S-T-I-	1004:1012	-N-S-T-I- at 36 amino acid	1004:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	70	from	acid	1026:1029	arg1	-N-G-T-V-					1032:1040	-N-G-T-V-	1032:1040	-N-G-T-V- at 237 amino acid	1032:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	70	from	acid	1026:1029	arg1	sites					1132:1136	the most possible N-glycosylation sites	1098:1136	the most possible N-glycosylation sites	1098:1136	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	1	71	theme	Genome	321:326	arg1	method					336:341	Genome Walking method	321:341	Genome Walking method	321:341	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	0	72	from	overproduction	89:102	arg1	viticola					119:126	viticola	119:126	viticola	119:126	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	2	73	theme	isoelectric	462:472	arg1	point					474:478	isoelectric point	462:478	isoelectric point: 5.01	462:484	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	6	74	gly	glycosylation	971:983	arg2	sites					985:989	three potential N-linked glycosylation sites	946:989	three potential N-linked glycosylation sites	946:989	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	74	gly	glycosylation	971:983	arg2	three					946:950	three	946:950	three	946:950	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	7	75	from	acid	1577:1580	arg1	strain					1601:1606	P. viticola 152 strain	1585:1606	P. viticola 152 strain	1585:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	3	76	located	located	587:593	arg2	intronless					559:568	intronless	559:568	intronless	559:568	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	76	located	located	587:593	arg2	promoter					549:556	A putative promoter	538:556	A putative promoter (intronless) of the gene	538:581	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	76	located	located	587:593	arg2	located					587:593	located	587:593	located	587:593	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	3	76	located	located	587:593	arg1	-666bp					598:603	-666bp	598:603	-666bp	598:603	A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences.
28057501	1	77	theme	marine	270:275	arg1	algae					277:281	marine algae	270:281	marine algae	270:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	7	78	theme	optimal	1438:1444	arg1	concentration					1446:1458	optimal concentration	1438:1458	optimal concentration of CSL	1438:1465	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	2	79	theme	PYC	379:381	arg1	gene					383:386	The PYC gene	375:386	The PYC gene	375:386	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	0	80	theme	carboxylase	41:51	arg1	gene					53:56	pyruvate carboxylase gene	32:56	pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152	32:130	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	2	81	dep	point	474:478	arg1	5.01					481:484	5.01	481:484	5.01	481:484	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	4	82	theme	consensus	700:708	arg1	AATAAA					732:737	AATAAA	732:737	AATAAA	732:737	A consensus polyadenylation site (AATAAA) was also observed at +10bp downstream of the ORF.
28057501	4	82	theme	consensus	700:708	arg1	site					726:729	A consensus polyadenylation site	698:729	A consensus polyadenylation site (AATAAA)	698:738	A consensus polyadenylation site (AATAAA) was also observed at +10bp downstream of the ORF.
28057501	0	83	theme	responsible	58:68	arg1	gene					53:56	pyruvate carboxylase gene	32:56	pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152	32:130	Cloning and characterization of pyruvate carboxylase gene responsible for calcium malate overproduction in Penicillium viticola 152 and its expression analysis.
28057501	6	84	theme	glycosylation	971:983	arg1	sites					985:989	three potential N-linked glycosylation sites	946:989	three potential N-linked glycosylation sites	946:989	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	5	85	contain	had	879:881	arg1	protein					794:800	The protein	790:800	The protein deduced from the PYC gene	790:826	The protein deduced from the PYC gene had no signal peptide, was a homotetramer (4), and had the four functional domains.
28057501	5	85	contain	had	879:881	arg2	domains					903:909	the four functional domains	883:909	the four functional domains	883:909	The protein deduced from the PYC gene had no signal peptide, was a homotetramer (4), and had the four functional domains.
28057501	7	86	theme	production	1302:1311	arg1	medium					1313:1318	MA production medium	1299:1318	MA production medium supplemented with CSL	1299:1340	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	7	87	theme	viticola	1588:1595	arg1	strain					1601:1606	P. viticola 152 strain	1585:1606	P. viticola 152 strain	1585:1606	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	6	88	theme	potential	952:960	arg1	sites					985:989	three potential N-linked glycosylation sites	946:989	three potential N-linked glycosylation sites	946:989	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	2	89	dep	frame	360:364	arg1	number					399:404	accession number	389:404	accession number: KM593097	389:414	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	7	90	from	activity	1287:1294	arg1	medium					1313:1318	MA production medium	1299:1318	MA production medium supplemented with CSL	1299:1340	After expression of the PYC gene of P. viticola 152 in medium supplemented with CSL and biotin, it was found that the specific pyruvate carboxylase activity in MA production medium supplemented with CSL was much higher (0.5U/mg) than in MA medium supplemented with biotin (0.3U/mg), suggesting that optimal concentration of CSL is required for increased expression of the PYC gene, which is responsible for high level production of malic acid in P. viticola 152 strain.
28057501	1	91	theme	fungus	224:229	arg1	viticola					243:250	fungus Penicillium viticola 152	224:254	a marine fungus Penicillium viticola 152 isolated from marine algae	215:281	In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method.
28057501	2	92	theme	open	347:350	arg1	ORF					367:369	ORF	367:369	ORF	367:369	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	2	92	theme	open	347:350	arg1	frame					360:364	An open reading frame	344:364	An open reading frame (ORF) of The PYC gene (accession number: KM593097)	344:415	An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa.
28057501	6	93	from	acid	1088:1091	arg1	-N-G-S-S-					1065:1073	-N-G-S-S-	1065:1073	-N-G-S-S- at 517 amino acid	1065:1091	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	93	from	acid	1088:1091	arg1	-N-S-T-I-					1004:1012	-N-S-T-I-	1004:1012	-N-S-T-I- at 36 amino acid	1004:1029	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	93	from	acid	1088:1091	arg1	-N-G-T-V-					1032:1040	-N-G-T-V-	1032:1040	-N-G-T-V- at 237 amino acid	1032:1058	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
28057501	6	93	from	acid	1088:1091	arg1	sites					1132:1136	the most possible N-glycosylation sites	1098:1136	the most possible N-glycosylation sites	1098:1136	Furthermore, PYC protein also had three potential N-linked glycosylation sites, among them, -N-S-T-I- at 36 amino acid, -N-G-T-V- at 237 amino acid, and -N-G-S-S- at 517 amino acid were the most possible N-glycosylation sites.
27728760	4	0	gly	glycoproteins	805:817	arg1	glycoproteins					805:817	the glycoproteins	801:817	the glycoproteins on the surface of the suppressor cells that released them	801:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	1	1	gly	glycoproteins	155:167	arg1	glycoproteins					155:167	glycoproteins	155:167	glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs)	155:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	4	2	from	glycoproteins	805:817	arg1	surface					826:832	the surface	822:832	the surface of the suppressor cells that released them	822:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	3	gly	N-glycoproteins	759:773	arg1	N-glycoproteins					759:773	the exosome surface N-glycoproteins	739:773	the exosome surface N-glycoproteins	739:773	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	3	gly	N-glycoproteins	759:773	arg1	subset					791:796	a subset	789:796	a subset of the glycoproteins on the surface of the suppressor cells that released them	789:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	4	theme	related	905:911	arg1	potential					913:921	related potential	905:921	related potential	905:921	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	3	5	theme	glycoprotein	552:563	arg1	identities					565:574	These glycoprotein identities	546:574	These glycoprotein identities	546:574	These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells.
27728760	2	6	theme	carcinoma-induced	521:537	arg1	MDSCs					539:543	mouse mammary carcinoma-induced MDSCs	507:543	mouse mammary carcinoma-induced MDSCs	507:543	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	1	7	theme	MDSCs	350:354	arg1	migration					337:345	migration	337:345	migration of MDSCs	337:354	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	7	theme	MDSCs	350:354	arg1	chemotaxis					322:331	exosome-mediated chemotaxis	305:331	exosome-mediated chemotaxis	305:331	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	5	8	dep	CD47	975:978	arg1	detected					1108:1115	detected	1108:1115	were among the surface N-glycoproteins detected	1069:1115	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	4	9	theme	exosome	743:749	arg1	N-glycoproteins					759:773	the exosome surface N-glycoproteins	739:773	the exosome surface N-glycoproteins	739:773	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	9	theme	exosome	743:749	arg1	subset					791:796	a subset	789:796	a subset of the glycoproteins on the surface of the suppressor cells that released them	789:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	2	10	theme	mammary	513:519	arg1	MDSCs					539:543	mouse mammary carcinoma-induced MDSCs	507:543	mouse mammary carcinoma-induced MDSCs	507:543	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	5	11	theme	surface	1084:1090	arg1	N-glycoproteins					1092:1106	the surface N-glycoproteins	1080:1106	the surface N-glycoproteins	1080:1106	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	6	12	theme	MDSC	1268:1271	arg1	chemotaxis					1273:1282	exosome-mediated MDSC chemotaxis	1251:1282	exosome-mediated MDSC chemotaxis	1251:1282	Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.
27728760	2	13	theme	method	414:419	arg1	modification					378:389	successful modification	367:389	successful modification of a surface chemistry method for use with exosomes	367:441	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	4	14	theme	glycoproteins	805:817	arg1	N-glycoproteins					759:773	the exosome surface N-glycoproteins	739:773	the exosome surface N-glycoproteins	739:773	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	14	theme	glycoproteins	805:817	arg1	subset					791:796	a subset	789:796	a subset of the glycoproteins on the surface of the suppressor cells that released them	789:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	2	15	theme	mouse	507:511	arg1	MDSCs					539:543	mouse mammary carcinoma-induced MDSCs	507:543	mouse mammary carcinoma-induced MDSCs	507:543	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	2	16	from	N-glycoproteins	467:481	arg1	exosomes					486:493	exosomes	486:493	exosomes released by mouse mammary carcinoma-induced MDSCs	486:543	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	6	17	theme	exosome-mediated	1251:1266	arg1	chemotaxis					1273:1282	exosome-mediated MDSC chemotaxis	1251:1282	exosome-mediated MDSC chemotaxis	1251:1282	Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.
27728760	2	18	with	method	414:419	arg1	exosomes					434:441	exosomes	434:441	exosomes	434:441	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	4	19	with	subset	791:796	arg1	functions					891:899	related functions	883:899	related functions	883:899	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	19	with	subset	791:796	arg1	potential					913:921	related potential	905:921	related potential	905:921	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	19	with	subset	791:796	arg1	proteomes					708:716	the lysate proteomes	697:716	the lysate proteomes examined previously	697:736	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	0	20	theme	Surface	0:6	arg1	Glycoproteins					8:20	Surface Glycoproteins	0:20	Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells	0:73	Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function.
27728760	1	21	link	myeloid-derived	209:223	arg1	cells					236:240	myeloid-derived suppressor cells	209:240	myeloid-derived suppressor cells (MDSCs)	209:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	21	link	myeloid-derived	209:223	arg1	MDSCs					243:247	MDSCs	243:247	MDSCs	243:247	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	5	22	theme	regulatory	1040:1049	arg1	protein					1051:1057	signal regulatory protein α	1033:1059	signal regulatory protein α (SIRPα)	1033:1067	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	5	22	theme	regulatory	1040:1049	arg1	SIRPα					1062:1066	SIRPα	1062:1066	SIRPα	1062:1066	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	2	23	theme	successful	367:376	arg1	modification					378:389	successful modification	367:389	successful modification of a surface chemistry method for use with exosomes	367:441	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	0	24	theme	Exosomes	25:32	arg1	Glycoproteins					8:20	Surface Glycoproteins	0:20	Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells	0:73	Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function.
27728760	4	25	from	subset	791:796	arg1	surface					826:832	the surface	822:832	the surface of the suppressor cells that released them	822:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	26	theme	related	883:889	arg1	functions					891:899	related functions	883:899	related functions	883:899	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	27	theme	suppressor	841:850	arg1	cells					852:856	the suppressor cells	837:856	the suppressor cells that released them	837:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	3	28	gly	glycoproteins	626:638	arg1	glycoproteins					626:638	93 N-linked glycoproteins	614:638	93 N-linked glycoproteins identified on the surface of the parental cells	614:686	These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells.
27728760	4	29	from	surface	826:832	arg1	N-glycoproteins					759:773	the exosome surface N-glycoproteins	739:773	the exosome surface N-glycoproteins	739:773	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	29	from	surface	826:832	arg1	subset					791:796	a subset	789:796	a subset of the glycoproteins on the surface of the suppressor cells that released them	789:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	3	30	theme	parental	673:680	arg1	cells					682:686	the parental cells	669:686	the parental cells	669:686	These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells.
27728760	5	31	theme	"	964:964	arg1	CD47					975:978	me" molecule CD47	962:978	me" molecule CD47	962:978	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	1	32	theme	exosomes	187:194	arg1	surface					176:182	the surface	172:182	the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs)	172:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	33	theme	selected	268:275	arg1	glycoproteins					277:289	selected glycoproteins	268:289	selected glycoproteins	268:289	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	3	34	theme	cells	682:686	arg1	surface					658:664	the surface	654:664	the surface of the parental cells	654:686	These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells.
27728760	3	35	theme	N-linked	617:624	arg1	glycoproteins					626:638	93 N-linked glycoproteins	614:638	93 N-linked glycoproteins identified on the surface of the parental cells	614:686	These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells.
27728760	5	36	gly	N-glycoproteins	1092:1106	arg1	N-glycoproteins					1092:1106	the surface N-glycoproteins	1080:1106	the surface N-glycoproteins	1080:1106	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	2	37	theme	chemistry	404:412	arg1	method					414:419	a surface chemistry method	394:419	a surface chemistry method for use with exosomes	394:441	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	2	38	theme	surface	459:465	arg1	N-glycoproteins					467:481	21 surface N-glycoproteins	456:481	21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs	456:543	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	2	39	gly	N-glycoproteins	467:481	arg1	N-glycoproteins					467:481	21 surface N-glycoproteins	456:481	21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs	456:543	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	2	40	theme	surface	396:402	arg1	method					414:419	a surface chemistry method	394:419	a surface chemistry method for use with exosomes	394:441	We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs.
27728760	0	41	theme	Suppressor	58:67	arg1	Cells					69:73	Myeloid-Derived Suppressor Cells	42:73	Myeloid-Derived Suppressor Cells	42:73	Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function.
27728760	6	42	theme	Functional	1118:1127	arg1	bioassays					1129:1137	Functional bioassays	1118:1137	Functional bioassays using antibodies to these three molecules	1118:1179	Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.
27728760	0	43	theme	Myeloid-Derived	42:56	arg1	Cells					69:73	Myeloid-Derived Suppressor Cells	42:73	Myeloid-Derived Suppressor Cells	42:73	Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function.
27728760	5	44	theme	signal	1033:1038	arg1	protein					1051:1057	signal regulatory protein α	1033:1059	signal regulatory protein α (SIRPα)	1033:1067	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	5	44	theme	signal	1033:1038	arg1	SIRPα					1062:1066	SIRPα	1062:1066	SIRPα	1062:1066	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	4	45	theme	cells	852:856	arg1	surface					826:832	the surface	822:832	the surface of the suppressor cells that released them	822:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	1	46	theme	exosome-mediated	305:320	arg1	chemotaxis					322:331	exosome-mediated chemotaxis	305:331	exosome-mediated chemotaxis	305:331	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	5	47	theme	binding	988:994	arg1	partners					996:1003	its binding partners	984:1003	its binding partners	984:1003	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	6	48	theme	lesser	1220:1225	arg1	extent					1227:1232	a lesser extent	1218:1232	a lesser extent	1218:1232	Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.
27728760	4	49	theme	surface	751:757	arg1	N-glycoproteins					759:773	the exosome surface N-glycoproteins	739:773	the exosome surface N-glycoproteins	739:773	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	4	49	theme	surface	751:757	arg1	subset					791:796	a subset	789:796	a subset of the glycoproteins on the surface of the suppressor cells that released them	789:875	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	5	50	theme	me	962:963	arg1	CD47					975:978	me" molecule CD47	962:978	me" molecule CD47	962:978	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	1	51	theme	myeloid-derived	209:223	arg1	cells					236:240	myeloid-derived suppressor cells	209:240	myeloid-derived suppressor cells (MDSCs)	209:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	51	theme	myeloid-derived	209:223	arg1	MDSCs					243:247	MDSCs	243:247	MDSCs	243:247	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	4	52	theme	therapeutic	926:936	arg1	targets					938:944	therapeutic targets	926:944	therapeutic targets	926:944	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	5	53	theme	molecule	966:973	arg1	CD47					975:978	me" molecule CD47	962:978	me" molecule CD47	962:978	The "don't eat me" molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected.
27728760	4	54	theme	lysate	701:706	arg1	proteomes					708:716	the lysate proteomes	697:716	the lysate proteomes examined previously	697:736	As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets.
27728760	1	55	theme	suppressor	225:234	arg1	cells					236:240	myeloid-derived suppressor cells	209:240	myeloid-derived suppressor cells (MDSCs)	209:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	55	theme	suppressor	225:234	arg1	MDSCs					243:247	MDSCs	243:247	MDSCs	243:247	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	56	attach	derived	196:202	arg1	cells					236:240	myeloid-derived suppressor cells	209:240	myeloid-derived suppressor cells (MDSCs)	209:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	56	attach	derived	196:202	arg2	exosomes					187:194	exosomes	187:194	exosomes derived from myeloid-derived suppressor cells (MDSCs)	187:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	56	attach	derived	196:202	arg1	MDSCs					243:247	MDSCs	243:247	MDSCs	243:247	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	57	gly	glycoproteins	277:289	arg1	glycoproteins					277:289	selected glycoproteins	268:289	selected glycoproteins	268:289	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	1	58	theme	proteomic	124:132	arg1	strategy					134:141	a proteomic strategy	122:141	a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs)	122:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	3	59	link	N-linked	617:624	arg1	glycoproteins					626:638	93 N-linked glycoproteins	614:638	93 N-linked glycoproteins identified on the surface of the parental cells	614:686	These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells.
27728760	1	60	from	glycoproteins	155:167	arg1	surface					176:182	the surface	172:182	the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs)	172:248	In this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs.
27728760	3	61	gly	glycoprotein	552:563	arg1	glycoprotein					552:563	These glycoprotein identities	546:574	These glycoprotein identities	546:574	These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells.
28748269	7	0	from	mice	964:967	arg1	saliva					948:953	the saliva	944:953	the saliva from NOD mice	944:967	BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the control mice, indicating individual constitution.
28748269	4	1	theme	parotid	598:604	arg1	glands					606:611	parotid glands	598:611	parotid glands from NOD mice	598:625	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	6	2	theme	protein	866:872	arg1	expression					845:854	The expression	841:854	The expression of BPIFB1 protein	841:872	The expression of BPIFB1 protein was also demonstrated by immunohistochemistry.
28748269	2	3	theme	protein	385:391	arg1	levels					393:398	the protein levels	381:398	the protein levels	381:398	However, we did not previously assess the protein levels.
28748269	8	4	from	BPIFB1	1050:1055	arg1	saliva					1060:1065	saliva	1060:1065	saliva	1060:1065	BPIFB1 in saliva may be applied to other research as a diagnostic marker.
28748269	1	5	theme	antibacterial	124:136	arg1	protein					138:144	an antibacterial protein	121:144	an antibacterial protein in the palate, lung, and nasal epithelium clone protein family	121:207	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	5	theme	antibacterial	124:136	arg1	BPIFB1					104:109	BPIFB1	104:109	BPIFB1 (Bpifb1)	104:118	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	3	6	from	expression	434:443	arg1	glands					478:483	the parotid glands	466:483	the parotid glands of NOD mice	466:495	In this report, we confirmed the expression of BPIFB1 protein in the parotid glands of NOD mice.
28748269	6	7	theme	BPIFB1	859:864	arg1	protein					866:872	BPIFB1 protein	859:872	BPIFB1 protein	859:872	The expression of BPIFB1 protein was also demonstrated by immunohistochemistry.
28748269	4	8	from	granules	586:593	arg1	glands					606:611	parotid glands	598:611	parotid glands from NOD mice	598:625	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	4	8	from	granules	586:593	arg1	mice					622:625	NOD mice	618:625	NOD mice	618:625	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	0	9	from	Presence	0:7	arg1	mice					53:56	non-obese diabetic mice	34:56	non-obese diabetic mice	34:56	Presence of BPIFB1 in saliva from non-obese diabetic mice.
28748269	0	9	from	Presence	0:7	arg1	saliva					22:27	saliva	22:27	saliva from non-obese diabetic mice	22:56	Presence of BPIFB1 in saliva from non-obese diabetic mice.
28748269	5	10	theme	molecular	823:831	arg1	weight					833:838	molecular weight	823:838	molecular weight	823:838	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	1	11	dep	diabetic	261:268	arg1	NOD/ShiJcl					276:285	NOD/ShiJcl	276:285	NOD/ShiJcl	276:285	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	11	dep	diabetic	261:268	arg1	NOD					271:273	NOD	271:273	NOD	271:273	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	7	12	from	mice	1008:1011	arg1	saliva					984:989	the saliva	980:989	the saliva from the control mice	980:1011	BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the control mice, indicating individual constitution.
28748269	4	13	theme	subcellular	516:526	arg1	fractions					528:536	subcellular fractions	516:536	subcellular fractions	516:536	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	5	14	theme	Aleuria	733:739	arg1	lectin					750:755	Aleuria aurantia lectin	733:755	Aleuria aurantia lectin	733:755	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	1	15	from	cells	242:246	arg1	model					313:317	an animal model	303:317	an animal model for Sjögren's syndrome	303:340	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	15	from	cells	242:246	arg1	mice					288:291	non-obese diabetic (NOD, NOD/ShiJcl) mice	251:291	non-obese diabetic (NOD, NOD/ShiJcl) mice	251:291	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	4	16	theme	parotid	650:656	arg1	glands					658:663	parotid glands	650:663	parotid glands from the control mice	650:685	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	5	17	theme	aurantia	741:748	arg1	lectin					750:755	Aleuria aurantia lectin	733:755	Aleuria aurantia lectin	733:755	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	7	18	theme	individual	1025:1034	arg1	constitution					1036:1047	individual constitution	1025:1047	individual constitution	1025:1047	BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the control mice, indicating individual constitution.
28748269	7	19	theme	NOD	960:962	arg1	mice					964:967	NOD mice	960:967	NOD mice	960:967	BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the control mice, indicating individual constitution.
28748269	5	20	theme	different	806:814	arg1	pI					816:817	a slightly different pI	795:817	a slightly different pI	795:817	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	8	21	theme	diagnostic	1105:1114	arg1	marker					1116:1121	a diagnostic marker	1103:1121	a diagnostic marker	1103:1121	BPIFB1 in saliva may be applied to other research as a diagnostic marker.
28748269	8	21	theme	diagnostic	1105:1114	arg1	BPIFB1					1050:1055	BPIFB1	1050:1055	BPIFB1 in saliva	1050:1065	BPIFB1 in saliva may be applied to other research as a diagnostic marker.
28748269	1	22	theme	palate	153:158	arg1	family					202:207	the palate, lung, and nasal epithelium clone protein family	149:207	the palate, lung, and nasal epithelium clone protein family	149:207	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	23	theme	parotid	227:233	arg1	cells					242:246	parotid acinar cells	227:246	parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome	227:340	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	24	theme	mRNA	85:88	arg1	expression					90:99	mRNA expression	85:99	mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family,	85:208	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	4	25	theme	fractions	528:536	arg1	Immunoblotting					498:511	Immunoblotting	498:511	Immunoblotting of subcellular fractions	498:536	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	0	26	theme	BPIFB1	12:17	arg1	Presence					0:7	Presence	0:7	Presence of BPIFB1 in saliva from non-obese diabetic mice.	0:57	Presence of BPIFB1 in saliva from non-obese diabetic mice.
28748269	1	27	theme	acinar	235:240	arg1	cells					242:246	parotid acinar cells	227:246	parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome	227:340	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	3	28	theme	protein	455:461	arg1	expression					434:443	the expression	430:443	the expression of BPIFB1 protein in the parotid glands of NOD mice	430:495	In this report, we confirmed the expression of BPIFB1 protein in the parotid glands of NOD mice.
28748269	1	29	theme	lung	161:164	arg1	family					202:207	the palate, lung, and nasal epithelium clone protein family	149:207	the palate, lung, and nasal epithelium clone protein family	149:207	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	7	30	theme	control	1000:1006	arg1	mice					1008:1011	the control mice	996:1011	the control mice	996:1011	BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the control mice, indicating individual constitution.
28748269	5	31	theme	spots	784:788	arg1	types					775:779	two types	771:779	two types of spots	771:788	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	1	32	theme	animal	306:311	arg1	model					313:317	an animal model	303:317	an animal model for Sjögren's syndrome	303:340	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	32	theme	animal	306:311	arg1	mice					288:291	non-obese diabetic (NOD, NOD/ShiJcl) mice	251:291	non-obese diabetic (NOD, NOD/ShiJcl) mice	251:291	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	7	33	located	detected	932:939	arg2	BPIFB1					921:926	BPIFB1	921:926	BPIFB1	921:926	BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the control mice, indicating individual constitution.
28748269	7	33	located	detected	932:939	arg1	saliva					948:953	the saliva	944:953	the saliva from NOD mice	944:967	BPIFB1 was detected in the saliva from NOD mice but not in the saliva from the control mice, indicating individual constitution.
28748269	1	34	dep	palate	153:158	arg1	the					149:151	the	149:151	the	149:151	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	0	35	theme	diabetic	44:51	arg1	mice					53:56	non-obese diabetic mice	34:56	non-obese diabetic mice	34:56	Presence of BPIFB1 in saliva from non-obese diabetic mice.
28748269	5	36	theme	N-linked	699:706	arg1	glycan					708:713	N-linked glycan	699:713	N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight	699:838	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	0	37	from	mice	53:56	arg1	Presence					0:7	Presence	0:7	Presence of BPIFB1 in saliva from non-obese diabetic mice.	0:57	Presence of BPIFB1 in saliva from non-obese diabetic mice.
28748269	0	37	from	mice	53:56	arg1	saliva					22:27	saliva	22:27	saliva from non-obese diabetic mice	22:56	Presence of BPIFB1 in saliva from non-obese diabetic mice.
28748269	3	38	theme	parotid	470:476	arg1	glands					478:483	the parotid glands	466:483	the parotid glands of NOD mice	466:495	In this report, we confirmed the expression of BPIFB1 protein in the parotid glands of NOD mice.
28748269	0	39	theme	non-obese	34:42	arg1	mice					53:56	non-obese diabetic mice	34:56	non-obese diabetic mice	34:56	Presence of BPIFB1 in saliva from non-obese diabetic mice.
28748269	1	40	theme	diabetic	261:268	arg1	model					313:317	an animal model	303:317	an animal model for Sjögren's syndrome	303:340	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	40	theme	diabetic	261:268	arg1	mice					288:291	non-obese diabetic (NOD, NOD/ShiJcl) mice	251:291	non-obese diabetic (NOD, NOD/ShiJcl) mice	251:291	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	1	41	theme	BPIFB1	104:109	arg1	expression					90:99	mRNA expression	85:99	mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family,	85:208	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	4	42	from	mice	622:625	arg1	granules					586:593	secretory granules	576:593	secretory granules in parotid glands from NOD mice	576:625	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	4	42	from	mice	622:625	arg1	glands					606:611	parotid glands	598:611	parotid glands from NOD mice	598:625	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	3	43	theme	NOD	488:490	arg1	mice					492:495	NOD mice	488:495	NOD mice	488:495	In this report, we confirmed the expression of BPIFB1 protein in the parotid glands of NOD mice.
28748269	3	44	theme	BPIFB1	448:453	arg1	protein					455:461	BPIFB1 protein	448:461	BPIFB1 protein	448:461	In this report, we confirmed the expression of BPIFB1 protein in the parotid glands of NOD mice.
28748269	1	45	theme	nasal	171:175	arg1	epithelium					177:186	nasal epithelium	171:186	nasal epithelium	171:186	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	5	46	link	N-linked	699:706	arg1	glycan					708:713	N-linked glycan	699:713	N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight	699:838	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	4	47	from	mice	682:685	arg1	glands					658:663	parotid glands	650:663	parotid glands from the control mice	650:685	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	4	48	theme	NOD	618:620	arg1	mice					622:625	NOD mice	618:625	NOD mice	618:625	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	1	49	theme	epithelium	177:186	arg1	family					202:207	the palate, lung, and nasal epithelium clone protein family	149:207	the palate, lung, and nasal epithelium clone protein family	149:207	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	3	50	theme	mice	492:495	arg1	glands					478:483	the parotid glands	466:483	the parotid glands of NOD mice	466:495	In this report, we confirmed the expression of BPIFB1 protein in the parotid glands of NOD mice.
28748269	5	51	contain	had	695:697	arg1	BPIFB1					688:693	BPIFB1	688:693	BPIFB1	688:693	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	5	51	contain	had	695:697	arg2	glycan					708:713	N-linked glycan	699:713	N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight	699:838	BPIFB1 had N-linked glycan that reacted with Aleuria aurantia lectin, which caused two types of spots with a slightly different pI and molecular weight.
28748269	8	52	theme	other	1085:1089	arg1	research					1091:1098	other research	1085:1098	other research	1085:1098	BPIFB1 in saliva may be applied to other research as a diagnostic marker.
28748269	1	53	theme	clone	188:192	arg1	family					202:207	the palate, lung, and nasal epithelium clone protein family	149:207	the palate, lung, and nasal epithelium clone protein family	149:207	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	4	54	theme	control	674:680	arg1	mice					682:685	the control mice	670:685	the control mice	670:685	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	1	55	from	protein	138:144	arg1	family					202:207	the palate, lung, and nasal epithelium clone protein family	149:207	the palate, lung, and nasal epithelium clone protein family	149:207	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28748269	4	56	theme	secretory	576:584	arg1	granules					586:593	secretory granules	576:593	secretory granules in parotid glands from NOD mice	576:625	Immunoblotting of subcellular fractions revealed that BPIBB1 was localised in secretory granules in parotid glands from NOD mice, and was almost not in parotid glands from the control mice.
28748269	1	57	theme	protein	194:200	arg1	family					202:207	the palate, lung, and nasal epithelium clone protein family	149:207	the palate, lung, and nasal epithelium clone protein family	149:207	We previously showed that mRNA expression of BPIFB1 (Bpifb1), an antibacterial protein in the palate, lung, and nasal epithelium clone protein family, was increased in parotid acinar cells in non-obese diabetic (NOD, NOD/ShiJcl) mice, which is an animal model for Sjögren's syndrome.
28687873	6	0	theme	sialic	955:960	arg1	binding					1135:1141	NDV binding	1131:1141	NDV binding	1131:1141	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	0	theme	sialic	955:960	arg1	effect					1158:1163	cytopathic effect	1147:1163	cytopathic effect	1147:1163	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	0	theme	sialic	955:960	arg1	receptor					993:1000	a high-affinity receptor	977:1000	a high-affinity receptor for NDV	977:1008	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	0	theme	sialic	955:960	arg1	acid					962:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	7	1	theme	cell	1286:1289	arg1	α2,6-sialylation					1299:1314	cell surface α2,6-sialylation	1286:1314	cell surface α2,6-sialylation	1286:1314	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	0	2	with	virotherapy	80:90	arg1	virus					115:119	Newcastle disease virus	97:119	Newcastle disease virus	97:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	2	3	theme	host	325:328	arg1	cells					330:334	host cells	325:334	host cells	325:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	5	4	dep	RESULTS	842:848	arg1	We					850:851	We	850:851	We	850:851	RESULTS We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells.
28687873	2	5	from	receptors	305:313	arg1	cells					330:334	host cells	325:334	host cells	325:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	8	6	from	evidence	1453:1460	arg1	virotherapy					1509:1519	oncolytic virotherapy	1499:1519	oncolytic virotherapy	1499:1519	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	0	7	link	α2,6-linked	0:10	arg1	acid					19:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	0	7	link	α2,6-linked	0:10	arg1	receptor					50:57	a high-affinity receptor	34:57	a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus	34:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	7	8	theme	α2,6-sialylation	1364:1379	arg1	low-level					1351:1359	low-level	1351:1359	low-level	1351:1359	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	5	9	theme	NDV	901:903	arg1	binding					905:911	NDV binding	901:911	NDV binding	901:911	RESULTS We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells.
28687873	7	10	with	cells	1331:1335	arg1	low-level					1351:1359	low-level	1351:1359	low-level	1351:1359	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	2	11	theme	sialic	293:298	arg1	receptors					305:313	the sialic acid receptors	289:313	the sialic acid receptors of NDV on host cells	289:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	8	12	from	strategy	1487:1494	arg1	virotherapy					1509:1519	oncolytic virotherapy	1499:1519	oncolytic virotherapy	1499:1519	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	6	13	theme	NDV	1131:1133	arg1	effect					1158:1163	cytopathic effect	1147:1163	cytopathic effect	1147:1163	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	13	theme	NDV	1131:1133	arg1	binding					1135:1141	NDV binding	1131:1141	NDV binding	1131:1141	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	13	theme	NDV	1131:1133	arg1	receptor					993:1000	a high-affinity receptor	977:1000	a high-affinity receptor for NDV	977:1008	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	13	theme	NDV	1131:1133	arg1	acid					962:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	4	14	theme	sialidases	725:734	arg1	transfection					740:751	transfection	740:751	transfection with sialyltransferase expression vector	740:792	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	4	14	theme	sialidases	725:734	arg1	Treatments					661:670	Treatments	661:670	Treatments of sialyltransferase inhibitors and linkage-specific sialidases	661:734	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	1	15	theme	PURPOSE	122:128	arg1	NDV					155:157	NDV	155:157	NDV	155:157	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	1	15	theme	PURPOSE	122:128	arg1	virus					148:152	PURPOSE Newcastle disease virus	122:152	PURPOSE Newcastle disease virus (NDV)	122:158	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	7	16	with	cells	1261:1265	arg1	high-level					1272:1281	high-level	1272:1281	high-level	1272:1281	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	3	17	gly	sialylated	544:553	arg1	analogues					571:579	sialylated glycan receptor analogues	544:579	sialylated glycan receptor analogues	544:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	1	18	theme	disease	140:146	arg1	NDV					155:157	NDV	155:157	NDV	155:157	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	1	18	theme	disease	140:146	arg1	virus					148:152	PURPOSE Newcastle disease virus	122:152	PURPOSE Newcastle disease virus (NDV)	122:158	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	2	19	from	substantiation	271:284	arg1	cells					330:334	host cells	325:334	host cells	325:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	6	20	theme	α2-6	1062:1065	arg1	linkage					1067:1073	α2-6 linkage	1062:1073	α2-6 linkage of sialylated N-linked glycans	1062:1104	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	8	21	theme	α2,6-sialylated	1541:1555	arg1	"					1587:1587	a "cellular marker"	1569:1587	a "cellular marker" for NDV	1569:1595	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	8	21	theme	α2,6-sialylated	1541:1555	arg1	receptor					1557:1564	α2,6-sialylated receptor	1541:1564	α2,6-sialylated receptor	1541:1564	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	4	22	theme	sialyltransferase	675:691	arg1	inhibitors					693:702	sialyltransferase inhibitors	675:702	sialyltransferase inhibitors	675:702	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	8	23	from	virotherapy	1509:1519	arg1	evidence					1453:1460	evidence	1453:1460	evidence of optimized therapeutic strategy in oncolytic virotherapy	1453:1519	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	0	24	theme	oncolytic	70:78	arg1	virotherapy					80:90	cancer oncolytic virotherapy	63:90	cancer oncolytic virotherapy with Newcastle disease virus	63:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	5	25	theme	cells	936:940	arg1	infection					917:925	infection	917:925	infection	917:925	RESULTS We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells.
28687873	5	25	theme	cells	936:940	arg1	binding					905:911	NDV binding	901:911	NDV binding	901:911	RESULTS We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells.
28687873	7	26	theme	carcinoma	1251:1259	arg1	cells					1261:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	8	27	theme	marker	1581:1586	arg1	"					1587:1587	a "cellular marker"	1569:1587	a "cellular marker" for NDV	1569:1595	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	8	27	theme	marker	1581:1586	arg1	receptor					1557:1564	α2,6-sialylated receptor	1541:1564	α2,6-sialylated receptor	1541:1564	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	2	28	theme	sialic	364:369	arg1	linkage					376:382	sialic acid linkage	364:382	sialic acid linkage	364:382	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	0	29	theme	disease	107:113	arg1	virus					115:119	Newcastle disease virus	97:119	Newcastle disease virus	97:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	3	30	with	analysis	503:510	arg1	analogues					571:579	sialylated glycan receptor analogues	544:579	sialylated glycan receptor analogues	544:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	31	theme	resonance	493:501	arg1	analysis					503:510	Surface plasmon resonance analysis	477:510	Surface plasmon resonance analysis	477:510	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	31	theme	resonance	493:501	arg1	METHODS					469:475	METHODS	469:475	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues	469:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	4	32	theme	sialyltransferase	758:774	arg1	vector					787:792	sialyltransferase expression vector	758:792	sialyltransferase expression vector	758:792	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	2	33	theme	preference	350:359	arg1	knowledge					337:345	knowledge	337:345	knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect	337:423	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	0	34	theme	α2,6-linked	0:10	arg1	acid					19:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	0	34	theme	α2,6-linked	0:10	arg1	receptor					50:57	a high-affinity receptor	34:57	a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus	34:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	2	35	theme	viral	387:391	arg1	attachment					393:402	viral attachment	387:402	viral attachment	387:402	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	6	36	theme	N-linked	1089:1096	arg1	glycans					1098:1104	sialylated N-linked glycans	1078:1104	sialylated N-linked glycans	1078:1104	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	3	37	theme	sialic	639:644	arg1	receptor					651:658	sialic acid receptor	639:658	sialic acid receptor	639:658	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	2	38	theme	linkage	376:382	arg1	preference					350:359	preference	350:359	preference of sialic acid linkage	350:382	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	7	39	theme	antitumor	1196:1204	arg1	effect					1206:1211	an enhanced antitumor effect	1184:1211	an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation,	1184:1380	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	0	40	theme	high-affinity	36:48	arg1	acid					19:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	0	40	theme	high-affinity	36:48	arg1	receptor					50:57	a high-affinity receptor	34:57	a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus	34:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	4	41	theme	acids	828:832	arg1	levels					834:839	sialic acids levels	821:839	sialic acids levels	821:839	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	1	42	theme	due	214:216	arg1	decades					206:212	decades	206:212	decades due to its naturally oncolytic property	206:252	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	2	43	theme	acid	371:374	arg1	linkage					376:382	sialic acid linkage	364:382	sialic acid linkage	364:382	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	8	44	theme	strategy	1487:1494	arg1	evidence					1453:1460	evidence	1453:1460	evidence of optimized therapeutic strategy in oncolytic virotherapy	1453:1519	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	3	45	theme	plasmon	485:491	arg1	resonance					493:501	Surface plasmon resonance	477:501	Surface plasmon resonance analysis	477:510	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	1	46	theme	oncolytic	235:243	arg1	property					245:252	its naturally oncolytic property	221:252	its naturally oncolytic property	221:252	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	6	47	theme	α2,6-linked	943:953	arg1	binding					1135:1141	NDV binding	1131:1141	NDV binding	1131:1141	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	47	theme	α2,6-linked	943:953	arg1	effect					1158:1163	cytopathic effect	1147:1163	cytopathic effect	1147:1163	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	47	theme	α2,6-linked	943:953	arg1	receptor					993:1000	a high-affinity receptor	977:1000	a high-affinity receptor for NDV	977:1008	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	47	theme	α2,6-linked	943:953	arg1	acid					962:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	7	48	theme	surface	1291:1297	arg1	α2,6-sialylation					1299:1314	cell surface α2,6-sialylation	1286:1314	cell surface α2,6-sialylation	1286:1314	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	3	49	theme	competitive	516:526	arg1	inhibition					528:537	competitive inhibition	516:537	competitive inhibition with sialylated glycan receptor analogues	516:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	49	theme	competitive	516:526	arg1	METHODS					469:475	METHODS	469:475	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues	469:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	2	50	theme	acid	300:303	arg1	receptors					305:313	the sialic acid receptors	289:313	the sialic acid receptors of NDV on host cells	289:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	8	51	dep	CONCLUSIONS	1422:1432	arg1	provides					1444:1451	provides	1444:1451	provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV	1444:1595	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	3	52	with	inhibition	528:537	arg1	analogues					571:579	sialylated glycan receptor analogues	544:579	sialylated glycan receptor analogues	544:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	2	53	from	cells	330:334	arg1	substantiation					271:284	the substantiation	267:284	the substantiation of the sialic acid receptors of NDV on host cells	267:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	6	54	link	N-linked	1089:1096	arg1	glycans					1098:1104	sialylated N-linked glycans	1078:1104	sialylated N-linked glycans	1078:1104	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	3	55	theme	glycan	555:560	arg1	analogues					571:579	sialylated glycan receptor analogues	544:579	sialylated glycan receptor analogues	544:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	2	56	from	knowledge	337:345	arg1	attachment					393:402	viral attachment	387:402	viral attachment	387:402	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	2	56	from	knowledge	337:345	arg1	effect					418:423	oncolytic effect	408:423	oncolytic effect	408:423	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	5	57	theme	sialic	871:876	arg1	acid					878:881	sialic acid	871:881	sialic acid	871:881	RESULTS We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells.
28687873	3	58	theme	receptor	562:569	arg1	analogues					571:579	sialylated glycan receptor analogues	544:579	sialylated glycan receptor analogues	544:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	8	59	theme	oncolytic	1499:1507	arg1	virotherapy					1509:1519	oncolytic virotherapy	1499:1519	oncolytic virotherapy	1499:1519	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	8	60	gly	α2,6-sialylated	1541:1555	arg1	"					1587:1587	a "cellular marker"	1569:1587	a "cellular marker" for NDV	1569:1595	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	8	60	gly	α2,6-sialylated	1541:1555	arg1	receptor					1557:1564	α2,6-sialylated receptor	1541:1564	α2,6-sialylated receptor	1541:1564	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	6	61	theme	high-affinity	979:991	arg1	binding					1135:1141	NDV binding	1131:1141	NDV binding	1131:1141	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	61	theme	high-affinity	979:991	arg1	effect					1158:1163	cytopathic effect	1147:1163	cytopathic effect	1147:1163	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	61	theme	high-affinity	979:991	arg1	receptor					993:1000	a high-affinity receptor	977:1000	a high-affinity receptor for NDV	977:1008	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	61	theme	high-affinity	979:991	arg1	acid					962:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	7	62	theme	colorectal	1240:1249	arg1	cells					1261:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	4	63	theme	linkage-specific	708:723	arg1	sialidases					725:734	linkage-specific sialidases	708:734	linkage-specific sialidases	708:734	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	8	64	theme	optimized	1465:1473	arg1	strategy					1487:1494	optimized therapeutic strategy	1465:1494	optimized therapeutic strategy in oncolytic virotherapy	1465:1519	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	1	65	theme	Newcastle	130:138	arg1	NDV					155:157	NDV	155:157	NDV	155:157	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	1	65	theme	Newcastle	130:138	arg1	virus					148:152	PURPOSE Newcastle disease virus	122:152	PURPOSE Newcastle disease virus (NDV)	122:158	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	3	66	used	used	586:589	arg2	analysis					503:510	Surface plasmon resonance analysis	477:510	Surface plasmon resonance analysis	477:510	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	66	used	used	586:589	arg2	inhibition					528:537	competitive inhibition	516:537	competitive inhibition with sialylated glycan receptor analogues	516:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	66	used	used	586:589	arg2	METHODS					469:475	METHODS	469:475	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues	469:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	0	67	theme	cancer	63:68	arg1	virotherapy					80:90	cancer oncolytic virotherapy	63:90	cancer oncolytic virotherapy with Newcastle disease virus	63:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	1	68	theme	oncolytic	180:188	arg1	virotherapy					190:200	oncolytic virotherapy	180:200	oncolytic virotherapy for decades due to its naturally oncolytic property	180:252	PURPOSE Newcastle disease virus (NDV) has been applied to oncolytic virotherapy for decades due to its naturally oncolytic property.
28687873	6	69	dep	ST6Gal	1018:1023	arg1	sialyltransferase					1027:1043	I sialyltransferase	1025:1043	the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells	1014:1120	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	5	70	theme	tumor	930:934	arg1	cells					936:940	tumor cells	930:940	tumor cells	930:940	RESULTS We demonstrated that sialic acid was essential for NDV binding and infection of tumor cells.
28687873	8	71	theme	cellular	1572:1579	arg1	"					1587:1587	a "cellular marker"	1569:1587	a "cellular marker" for NDV	1569:1595	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	8	71	theme	cellular	1572:1579	arg1	receptor					1557:1564	α2,6-sialylated receptor	1541:1564	α2,6-sialylated receptor	1541:1564	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	4	72	theme	inhibitors	693:702	arg1	transfection					740:751	transfection	740:751	transfection with sialyltransferase expression vector	740:792	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	4	72	theme	inhibitors	693:702	arg1	Treatments					661:670	Treatments	661:670	Treatments of sialyltransferase inhibitors and linkage-specific sialidases	661:734	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	0	73	theme	Newcastle	97:105	arg1	virus					115:119	Newcastle disease virus	97:119	Newcastle disease virus	97:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	3	74	theme	sialylated	544:553	arg1	analogues					571:579	sialylated glycan receptor analogues	544:579	sialylated glycan receptor analogues	544:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	7	75	from	effect	1206:1211	arg1	cells					1261:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	7	75	from	effect	1206:1211	arg1	cells					1331:1335	SW480 cells	1325:1335	SW480 cells with relative low-level of α2,6-sialylation	1325:1379	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	7	76	theme	aggressive	1223:1232	arg1	cells					1261:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	0	77	theme	sialic	12:17	arg1	acid					19:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid	0:22	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	0	77	theme	sialic	12:17	arg1	receptor					50:57	a high-affinity receptor	34:57	a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus	34:119	α2,6-linked sialic acid serves as a high-affinity receptor for cancer oncolytic virotherapy with Newcastle disease virus.
28687873	3	78	dep	METHODS	469:475	arg1	analysis					503:510	Surface plasmon resonance analysis	477:510	Surface plasmon resonance analysis	477:510	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	78	dep	METHODS	469:475	arg1	inhibition					528:537	competitive inhibition	516:537	competitive inhibition with sialylated glycan receptor analogues	516:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	78	dep	METHODS	469:475	arg1	METHODS					469:475	METHODS	469:475	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues	469:579	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	6	79	theme	CHO-K1	1109:1114	arg1	cells					1116:1120	CHO-K1 cells	1109:1120	CHO-K1 cells	1109:1120	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	2	80	theme	oncolytic	408:416	arg1	effect					418:423	oncolytic effect	408:423	oncolytic effect	408:423	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	3	81	theme	receptor	651:658	arg1	affinity					608:615	the affinity	604:615	the affinity	604:615	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	3	81	theme	receptor	651:658	arg1	preference					625:634	the preference	621:634	the preference of sialic acid receptor	621:658	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	6	82	theme	glycans	1098:1104	arg1	linkage					1067:1073	α2-6 linkage	1062:1073	α2-6 linkage of sialylated N-linked glycans	1062:1104	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	4	83	with	Treatments	661:670	arg1	vector					787:792	sialyltransferase expression vector	758:792	sialyltransferase expression vector	758:792	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	4	84	theme	expression	776:785	arg1	vector					787:792	sialyltransferase expression vector	758:792	sialyltransferase expression vector	758:792	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	6	85	theme	cytopathic	1147:1156	arg1	binding					1135:1141	NDV binding	1131:1141	NDV binding	1131:1141	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	85	theme	cytopathic	1147:1156	arg1	receptor					993:1000	a high-affinity receptor	977:1000	a high-affinity receptor for NDV	977:1008	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	85	theme	cytopathic	1147:1156	arg1	effect					1158:1163	cytopathic effect	1147:1163	cytopathic effect	1147:1163	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	85	theme	cytopathic	1147:1156	arg1	acid					962:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	7	86	theme	enhanced	1187:1194	arg1	effect					1206:1211	an enhanced antitumor effect	1184:1211	an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation,	1184:1380	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	6	87	theme	sialylated	1078:1087	arg1	glycans					1098:1104	sialylated N-linked glycans	1078:1104	sialylated N-linked glycans	1078:1104	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	88	link	α2,6-linked	943:953	arg1	binding					1135:1141	NDV binding	1131:1141	NDV binding	1131:1141	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	88	link	α2,6-linked	943:953	arg1	effect					1158:1163	cytopathic effect	1147:1163	cytopathic effect	1147:1163	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	88	link	α2,6-linked	943:953	arg1	receptor					993:1000	a high-affinity receptor	977:1000	a high-affinity receptor for NDV	977:1008	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	88	link	α2,6-linked	943:953	arg1	acid					962:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid	943:965	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	6	89	gly	sialylated	1078:1087	arg1	glycans					1098:1104	sialylated N-linked glycans	1078:1104	sialylated N-linked glycans	1078:1104	α2,6-linked sialic acid served as a high-affinity receptor for NDV and the ST6Gal I sialyltransferase that synthesizes α2-6 linkage of sialylated N-linked glycans in CHO-K1 cells promoted NDV binding and cytopathic effect.
28687873	7	90	theme	SW620	1234:1238	arg1	cells					1261:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	aggressive SW620 colorectal carcinoma cells	1223:1265	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	7	91	theme	SW480	1325:1329	arg1	cells					1331:1335	SW480 cells	1325:1335	SW480 cells with relative low-level of α2,6-sialylation	1325:1379	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	3	92	theme	Surface	477:483	arg1	resonance					493:501	Surface plasmon resonance	477:501	Surface plasmon resonance analysis	477:510	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	2	93	theme	NDV	318:320	arg1	receptors					305:313	the sialic acid receptors	289:313	the sialic acid receptors of NDV on host cells	289:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	3	94	theme	acid	646:649	arg1	receptor					651:658	sialic acid receptor	639:658	sialic acid receptor	639:658	METHODS Surface plasmon resonance analysis and competitive inhibition with sialylated glycan receptor analogues were used to determine the affinity and the preference of sialic acid receptor.
28687873	4	95	theme	sialic	821:826	arg1	acids					828:832	sialic acids	821:832	sialic acids levels	821:839	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	2	96	theme	receptors	305:313	arg1	substantiation					271:284	the substantiation	267:284	the substantiation of the sialic acid receptors of NDV on host cells	267:334	In spite of the substantiation of the sialic acid receptors of NDV on host cells, knowledge of preference of sialic acid linkage in viral attachment and oncolytic effect is lacking and imperative to be elucidated.
28687873	7	97	theme	α2,6-sialylation	1299:1314	arg1	high-level					1272:1281	high-level	1272:1281	high-level	1272:1281	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
28687873	4	98	with	transfection	740:751	arg1	vector					787:792	sialyltransferase expression vector	758:792	sialyltransferase expression vector	758:792	Treatments of sialyltransferase inhibitors and linkage-specific sialidases and transfection with sialyltransferase expression vector were performed to regulate sialic acids levels.
28687873	8	99	theme	therapeutic	1475:1485	arg1	strategy					1487:1494	optimized therapeutic strategy	1465:1494	optimized therapeutic strategy in oncolytic virotherapy	1465:1519	CONCLUSIONS The study provides evidence of optimized therapeutic strategy in oncolytic virotherapy via partly defining α2,6-sialylated receptor as a "cellular marker" for NDV.
28687873	7	100	theme	NDV	1216:1218	arg1	effect					1206:1211	an enhanced antitumor effect	1184:1211	an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation,	1184:1380	More importantly, an enhanced antitumor effect of NDV on aggressive SW620 colorectal carcinoma cells with high-level of cell surface α2,6-sialylation, but not SW480 cells with relative low-level of α2,6-sialylation, was observed both in vitro and in vivo.
27666939	4	0	theme	ovary	537:541	arg1	cells					554:558	the Chinese hamster ovary (CHO) host cells	517:558	the Chinese hamster ovary (CHO) host cells	517:558	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	2	1	link	N-linked	312:319	arg1	glycan					321:326	the antibody heavy chain's core N-linked glycan	280:326	the antibody heavy chain's core N-linked glycan	280:326	ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s).
27666939	1	2	theme	natural	236:242	arg1	cells					251:255	natural killer cells	236:255	natural killer cells	236:255	During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells.
27666939	7	3	theme	product	1342:1348	arg1	attributes					1358:1367	otherwise similar product quality attributes	1324:1367	otherwise similar product quality attributes	1324:1367	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	9	4	theme	production	1785:1794	arg1	media					1796:1800	the production media	1781:1800	the production media	1781:1800	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	4	5	theme	CHO	544:546	arg1	cells					554:558	the Chinese hamster ovary (CHO) host cells	517:558	the Chinese hamster ovary (CHO) host cells	517:558	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	5	6	theme	comparative	864:874	arg1	studies					876:882	comparative studies	864:882	comparative studies	864:882	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	4	7	theme	antibody	592:599	arg1	molecules					601:609	antibody molecules	592:609	antibody molecules with fully afucosylated glycans	592:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	9	8	dep	afucosylated	1731:1742	arg1	to					1728:1729	to	1728:1729	to	1728:1729	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	2	9	theme	antibody	284:291	arg1	chain					299:303	antibody heavy chain	284:303	the antibody heavy chain's core N-linked glycan	280:326	ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s).
27666939	8	10	theme	product	1617:1623	arg1	qualities					1625:1633	comparable product qualities	1606:1633	comparable product qualities	1606:1633	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	7	11	theme	afucosylated	1290:1301	arg1	profiles					1310:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	9	12	theme	intended	1822:1829	arg1	levels					1831:1836	intended levels	1822:1836	intended levels of FcγRIII-binding and ADCC for an antibody	1822:1880	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	5	13	theme	major	655:659	arg1	drawback					661:668	a major drawback	653:668	a major drawback of the FUT8-KO host	653:688	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	5	13	theme	major	655:659	arg1	requirement					697:707	the requirement	693:707	the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo	693:903	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	7	14	gly	fucosylated	1269:1279	arg1	profiles					1310:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	5	15	gly	fucosylated	808:818	arg1	species					852:858	both primarily fucosylated and fully afucosylated antibody species	793:858	both primarily fucosylated and fully afucosylated antibody species	793:858	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	4	16	gly	afucosylated	622:633	arg1	glycans					635:641	fully afucosylated glycans	616:641	fully afucosylated glycans	616:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	5	17	theme	antibody	843:850	arg1	species					852:858	both primarily fucosylated and fully afucosylated antibody species	793:858	both primarily fucosylated and fully afucosylated antibody species	793:858	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	9	18	theme	afucosylated	1731:1742	arg1	glycans					1744:1750	primarily fucosylated to afucosylated glycans	1706:1750	primarily fucosylated to afucosylated glycans	1706:1750	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	6	19	theme	fucosylated	951:961	arg1	clones					975:980	primarily fucosylated and FUT8-KO clones	941:980	primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation	941:1117	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	7	20	theme	antibody	1228:1235	arg1	molecules					1237:1245	antibody molecules	1228:1245	antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles	1228:1317	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	4	21	theme	afucosylated	622:633	arg1	glycans					635:641	fully afucosylated glycans	616:641	fully afucosylated glycans	616:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	7	22	with	molecules	1237:1245	arg1	profiles					1310:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	5	23	theme	fucosylated	808:818	arg1	species					852:858	both primarily fucosylated and fully afucosylated antibody species	793:858	both primarily fucosylated and fully afucosylated antibody species	793:858	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	9	24	theme	FXKO	1645:1648	arg1	clones					1650:1655	FXKO clones	1645:1655	FXKO clones	1645:1655	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	4	25	theme	efficient	459:467	arg1	approach					469:476	A commonly used and efficient approach	439:476	A commonly used and efficient approach	439:476	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	4	25	theme	efficient	459:467	arg1	knocking					487:494	knocking	487:494	knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans	487:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	1	26	theme	dependent	156:164	arg1	ADCC					185:188	ADCC	185:188	ADCC	185:188	During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells.
27666939	1	26	theme	dependent	156:164	arg1	cytotoxicity					171:182	antibody dependent cell cytotoxicity	147:182	antibody dependent cell cytotoxicity (ADCC)	147:189	During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells.
27666939	3	27	used	utilized	387:394	arg2	strategies					366:375	Several strategies	358:375	Several strategies	358:375	Several strategies have been utilized to generate fully afucosylated antibodies.
27666939	0	28	theme	antibodies	80:89	arg1	ratios					42:47	desired ratios	34:47	desired ratios of fucosylated or afucosylated antibodies	34:89	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	0	29	gly	fucosylated	52:62	arg1	antibodies					80:89	fucosylated or afucosylated antibodies	52:89	antibodies	80:89	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	5	30	theme	FUT8-KO	677:683	arg1	host					685:688	the FUT8-KO host	673:688	the FUT8-KO host	673:688	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	0	31	gly	afucosylated	67:78	arg1	antibodies					80:89	fucosylated or afucosylated antibodies	52:89	antibodies	80:89	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	6	32	theme	quality	1010:1016	arg1	attributes					1018:1027	product quality attributes	1002:1027	product quality attributes	1002:1027	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	4	33	theme	used	450:453	arg1	approach					469:476	A commonly used and efficient approach	439:476	A commonly used and efficient approach	439:476	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	4	33	theme	used	450:453	arg1	knocking					487:494	knocking	487:494	knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans	487:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	0	34	theme	fucosylated	52:62	arg1	antibodies					80:89	fucosylated or afucosylated antibodies	52:89	antibodies	80:89	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	5	35	theme	line	743:746	arg1	CLD					761:763	CLD	761:763	CLD	761:763	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	5	35	theme	line	743:746	arg1	development					748:758	cell line development	738:758	two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo	725:903	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	9	36	gly	afucosylated	1731:1742	arg1	glycans					1744:1750	primarily fucosylated to afucosylated glycans	1706:1750	primarily fucosylated to afucosylated glycans	1706:1750	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	8	37	theme	FXKO	1440:1443	arg1	host					1445:1448	the FXKO host	1436:1448	the FXKO host	1436:1448	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	0	38	theme	CHO	12:14	arg1	hosts					16:20	FX knockout CHO hosts	0:20	FX knockout CHO hosts	0:20	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	7	39	dep	knockout	1163:1170	arg1	FXKO					1173:1176	FXKO	1173:1176	FXKO	1173:1176	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	4	40	with	molecules	601:609	arg1	glycans					635:641	fully afucosylated glycans	616:641	fully afucosylated glycans	616:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	7	41	theme	cell	1188:1191	arg1	line					1193:1196	a FX knockout (FXKO) CHO host cell line	1158:1196	a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes	1158:1367	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	7	41	theme	cell	1188:1191	arg1	capable					1206:1212	capable	1206:1212	capable	1206:1212	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	12	42	dep	632-644	1913:1919	arg1	2017					1903:1906	2017	1903:1906	2017	1903:1906	2017;114: 632-644.
27666939	3	43	gly	afucosylated	414:425	arg1	antibodies					427:436	fully afucosylated antibodies	408:436	fully afucosylated antibodies	408:436	Several strategies have been utilized to generate fully afucosylated antibodies.
27666939	2	44	theme	N-linked	312:319	arg1	glycan					321:326	the antibody heavy chain's core N-linked glycan	280:326	the antibody heavy chain's core N-linked glycan	280:326	ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s).
27666939	5	45	theme	separate	729:736	arg1	efforts					766:772	two separate cell line development (CLD) efforts	725:772	two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo	725:903	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	6	46	with	clones	975:980	arg1	similar					987:993	similar	987:993	similar	987:993	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	7	47	theme	CHO	1179:1181	arg1	line					1193:1196	a FX knockout (FXKO) CHO host cell line	1158:1196	a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes	1158:1367	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	7	47	theme	CHO	1179:1181	arg1	capable					1206:1212	capable	1206:1212	capable	1206:1212	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	9	48	theme	glycans	1744:1750	arg1	ratio					1697:1701	the desired ratio	1685:1701	the desired ratio of primarily fucosylated to afucosylated glycans	1685:1750	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	13	49	dep	©	1922:1922	arg1	Inc.					1948:1951	Inc.	1948:1951	Inc.	1948:1951	© 2016 Wiley Periodicals, Inc.
27666939	6	50	theme	observed	1048:1055	arg1	s					1072:1072	s	1072:1072	s	1072:1072	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	6	50	theme	observed	1048:1055	arg1	advantage					1062:1070	any observed ADCC advantage	1044:1070	any observed ADCC advantage(s)	1044:1073	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	3	51	theme	afucosylated	414:425	arg1	antibodies					427:436	fully afucosylated antibodies	408:436	fully afucosylated antibodies	408:436	Several strategies have been utilized to generate fully afucosylated antibodies.
27666939	2	52	theme	fucose	338:343	arg1	s					354:354	the fucose molecule(s)	334:355	the fucose molecule(s)	334:355	ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s).
27666939	8	53	dep	Hence	1429:1433	arg1	only					1454:1457	only	1454:1457	only	1454:1457	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	7	54	theme	fucose	1395:1400	arg1	addition					1383:1390	addition	1383:1390	addition of fucose to the cell culture media	1383:1426	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	7	55	theme	knockout	1163:1170	arg1	line					1193:1196	a FX knockout (FXKO) CHO host cell line	1158:1196	a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes	1158:1367	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	7	55	theme	knockout	1163:1170	arg1	capable					1206:1212	capable	1206:1212	capable	1206:1212	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	8	56	theme	separate	1504:1511	arg1	efforts					1517:1523	two separate CLD efforts	1500:1523	two separate CLD efforts	1500:1523	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	7	57	gly	afucosylated	1290:1301	arg1	profiles					1310:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	4	58	theme	hamster	529:535	arg1	cells					554:558	the Chinese hamster ovary (CHO) host cells	517:558	the Chinese hamster ovary (CHO) host cells	517:558	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	8	59	theme	many	1568:1571	arg1	colonies					1573:1580	many colonies	1568:1580	many colonies	1568:1580	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	1	60	theme	killer	244:249	arg1	cells					251:255	natural killer cells	236:255	natural killer cells	236:255	During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells.
27666939	7	61	theme	quality	1350:1356	arg1	attributes					1358:1367	otherwise similar product quality attributes	1324:1367	otherwise similar product quality attributes	1324:1367	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	1	62	theme	cell	166:169	arg1	ADCC					185:188	ADCC	185:188	ADCC	185:188	During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells.
27666939	1	62	theme	cell	166:169	arg1	cytotoxicity					171:182	antibody dependent cell cytotoxicity	147:182	antibody dependent cell cytotoxicity (ADCC)	147:189	During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells.
27666939	0	63	theme	desired	34:40	arg1	ratios					42:47	desired ratios	34:47	desired ratios of fucosylated or afucosylated antibodies	34:89	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	7	64	theme	similar	1334:1340	arg1	attributes					1358:1367	otherwise similar product quality attributes	1324:1367	otherwise similar product quality attributes	1324:1367	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	2	65	theme	heavy	293:297	arg1	chain					299:303	antibody heavy chain	284:303	the antibody heavy chain's core N-linked glycan	280:326	ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s).
27666939	7	66	theme	culture	1414:1420	arg1	media					1422:1426	the cell culture media	1405:1426	the cell culture media	1405:1426	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	4	67	theme	molecules	601:609	arg1	expression					578:587	expression	578:587	expression of antibody molecules with fully afucosylated glycans	578:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	0	68	theme	comparable	112:121	arg1	quality					131:137	comparable product quality	112:137	comparable product quality	112:137	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	8	69	theme	comparable	1606:1615	arg1	qualities					1625:1633	comparable product qualities	1606:1633	comparable product qualities	1606:1633	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	5	70	gly	afucosylated	830:841	arg1	species					852:858	both primarily fucosylated and fully afucosylated antibody species	793:858	both primarily fucosylated and fully afucosylated antibody species	793:858	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	7	71	theme	glycan	1303:1308	arg1	profiles					1310:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	9	72	with	antibodies	1669:1678	arg1	ratio					1697:1701	the desired ratio	1685:1701	the desired ratio of primarily fucosylated to afucosylated glycans	1685:1750	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	1	73	theme	target	195:200	arg1	cells					202:206	the target cells	191:206	the target cells	191:206	During antibody dependent cell cytotoxicity (ADCC) the target cells are killed by monocytes and natural killer cells.
27666939	9	74	theme	FcγRIII-binding	1841:1855	arg1	levels					1831:1836	intended levels	1822:1836	intended levels of FcγRIII-binding and ADCC for an antibody	1822:1880	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	6	75	theme	FUT8-KO	967:973	arg1	clones					975:980	primarily fucosylated and FUT8-KO clones	941:980	primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation	941:1117	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	5	76	theme	afucosylated	830:841	arg1	species					852:858	both primarily fucosylated and fully afucosylated antibody species	793:858	both primarily fucosylated and fully afucosylated antibody species	793:858	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	7	77	theme	fucosylated	1269:1279	arg1	profiles					1310:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	either primarily fucosylated or fully afucosylated glycan profiles	1252:1317	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	9	78	theme	ADCC	1861:1864	arg1	levels					1831:1836	intended levels	1822:1836	intended levels of FcγRIII-binding and ADCC for an antibody	1822:1880	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	5	79	theme	host	685:688	arg1	drawback					661:668	a major drawback	653:668	a major drawback of the FUT8-KO host	653:688	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	5	79	theme	host	685:688	arg1	requirement					697:707	the requirement	693:707	the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo	693:903	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	0	80	theme	afucosylated	67:78	arg1	antibodies					80:89	fucosylated or afucosylated antibodies	52:89	antibodies	80:89	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	8	81	with	clones	1594:1599	arg1	qualities					1625:1633	comparable product qualities	1606:1633	comparable product qualities	1606:1633	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	0	82	theme	knockout	3:10	arg1	hosts					16:20	FX knockout CHO hosts	0:20	FX knockout CHO hosts	0:20	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	3	83	theme	Several	358:364	arg1	strategies					366:375	Several strategies	358:375	Several strategies	358:375	Several strategies have been utilized to generate fully afucosylated antibodies.
27666939	6	84	theme	product	1002:1008	arg1	attributes					1018:1027	product quality attributes	1002:1027	product quality attributes	1002:1027	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	9	85	theme	desired	1689:1695	arg1	ratio					1697:1701	the desired ratio	1685:1701	the desired ratio of primarily fucosylated to afucosylated glycans	1685:1750	Finally, FXKO clones can express antibodies with the desired ratio of primarily fucosylated to afucosylated glycans when fucose is titrated into the production media, to allow achieving intended levels of FcγRIII-binding and ADCC for an antibody.
27666939	2	86	theme	molecule	345:352	arg1	s					354:354	the fucose molecule(s)	334:355	the fucose molecule(s)	334:355	ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s).
27666939	5	87	theme	development	748:758	arg1	efforts					766:772	two separate cell line development (CLD) efforts	725:772	two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo	725:903	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	7	88	theme	line	1193:1196	arg1	generation					1136:1145	generation	1136:1145	generation	1136:1145	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	7	88	theme	line	1193:1196	arg1	use					1151:1153	use	1151:1153	use	1151:1153	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	4	89	theme	Chinese	521:527	arg1	cells					554:558	the Chinese hamster ovary (CHO) host cells	517:558	the Chinese hamster ovary (CHO) host cells	517:558	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	7	90	theme	host	1183:1186	arg1	line					1193:1196	a FX knockout (FXKO) CHO host cell line	1158:1196	a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes	1158:1367	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	7	90	theme	host	1183:1186	arg1	capable					1206:1212	capable	1206:1212	capable	1206:1212	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	0	91	theme	high	96:99	arg1	titers					101:106	high titers	96:106	high titers	96:106	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	0	92	theme	product	123:129	arg1	quality					131:137	comparable product quality	112:137	comparable product quality	112:137	FX knockout CHO hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.
27666939	4	93	theme	FUT8	504:507	arg1	gene					509:512	the FUT8 gene	500:512	the FUT8 gene	500:512	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	2	94	theme	core	307:310	arg1	glycan					321:326	the antibody heavy chain's core N-linked glycan	280:326	the antibody heavy chain's core N-linked glycan	280:326	ADCC is enhanced when the antibody heavy chain's core N-linked glycan lacks the fucose molecule(s).
27666939	6	95	theme	ADCC	1057:1060	arg1	s					1072:1072	s	1072:1072	s	1072:1072	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	6	95	theme	ADCC	1057:1060	arg1	advantage					1062:1070	any observed ADCC advantage	1044:1070	any observed ADCC advantage(s)	1044:1073	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	4	96	theme	host	549:552	arg1	cells					554:558	the Chinese hamster ovary (CHO) host cells	517:558	the Chinese hamster ovary (CHO) host cells	517:558	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	6	97	gly	fucosylated	951:961	arg1	clones					975:980	primarily fucosylated and FUT8-KO clones	941:980	primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation	941:1117	Even more challenging is obtaining primarily fucosylated and FUT8-KO clones with similar enough product quality attributes to ensure that any observed ADCC advantage(s) can be strictly attributed to afucosylation.
27666939	7	98	theme	cell	1409:1412	arg1	media					1422:1426	the cell culture media	1405:1426	the cell culture media	1405:1426	Here, we report generation and use of a FX knockout (FXKO) CHO host cell line that is capable of expressing antibody molecules with either primarily fucosylated or fully afucosylated glycan profiles with otherwise similar product quality attributes, depending on addition of fucose to the cell culture media.
27666939	8	99	theme	CLD	1513:1515	arg1	efforts					1517:1523	two separate CLD efforts	1500:1523	two separate CLD efforts	1500:1523	Hence, the FXKO host not only obviates the requirement for undertaking two separate CLD efforts, but it also averts the need for screening many colonies to identify clones with comparable product qualities.
27666939	4	100	theme	cells	554:558	arg1	approach					469:476	A commonly used and efficient approach	439:476	A commonly used and efficient approach	439:476	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	4	100	theme	cells	554:558	arg1	knocking					487:494	knocking	487:494	knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans	487:641	A commonly used and efficient approach has been knocking out the FUT8 gene of the Chinese hamster ovary (CHO) host cells, which results in expression of antibody molecules with fully afucosylated glycans.
27666939	5	101	theme	cell	738:741	arg1	CLD					761:763	CLD	761:763	CLD	761:763	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
27666939	5	101	theme	cell	738:741	arg1	development					748:758	cell line development	738:758	two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo	725:903	However, a major drawback of the FUT8-KO host is the requirement for undertaking two separate cell line development (CLD) efforts in order to obtain both primarily fucosylated and fully afucosylated antibody species for comparative studies in vitro and in vivo.
26040437	4	0	theme	insect	848:853	arg1	cells					855:859	insect cells	848:859	insect cells	848:859	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	6	1	theme	HA1	1152:1154	arg1	protein					1156:1162	HA1 protein	1152:1162	HA1 protein	1152:1162	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	3	2	theme	Western	678:684	arg1	blot					686:689	Western blot	678:689	Western blot	678:689	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	10	3	theme	specific	1779:1786	arg1	detection					1788:1796	the specific detection	1775:1796	the specific detection of H5 avian influenza virus infection	1775:1834	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	4	4	theme	HA1	823:825	arg1	proteins					827:834	the recombinant HA1 proteins	807:834	the recombinant HA1 proteins produced in insect cells	807:859	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	3	5	theme	unglycosylated	533:546	arg1	precursor					548:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	4	6	theme	N-linked	891:898	arg1	chains					921:926	N-linked oligosaccharide side chains	891:926	N-linked oligosaccharide side chains	891:926	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	6	7	theme	high	1127:1130	arg1	yield					1132:1136	A high yield	1125:1136	A high yield	1125:1136	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	6	7	theme	high	1127:1130	arg1	37 μg/ml					1139:1146	37 μg/ml	1139:1146	37 μg/ml	1139:1146	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	1	8	theme	pathogenic	185:194	arg1	A/chicken/Vietnam/14/2005					228:252	A/chicken/Vietnam/14/2005	228:252	A/chicken/Vietnam/14/2005	228:252	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	1	8	theme	pathogenic	185:194	arg1	isolate					219:225	avian influenza (HPAI) isolate	196:225	highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005)	178:253	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	4	9	theme	side	916:919	arg1	chains					921:926	N-linked oligosaccharide side chains	891:926	N-linked oligosaccharide side chains	891:926	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	7	10	theme	hemadsorption	1376:1388	arg1	assays					1390:1395	hemadsorption assays	1376:1395	hemadsorption assays	1376:1395	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	1	11	theme	influenza	202:210	arg1	A/chicken/Vietnam/14/2005					228:252	A/chicken/Vietnam/14/2005	228:252	A/chicken/Vietnam/14/2005	228:252	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	1	11	theme	influenza	202:210	arg1	isolate					219:225	avian influenza (HPAI) isolate	196:225	highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005)	178:253	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	6	12	theme	baculovirus-infected	1194:1213	arg1	supernatant					1228:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	3	13	gly	unglycosylated	533:546	arg1	precursor					548:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	1	14	from	isolate	219:225	arg1	ectodomain					148:157	The hemagglutinin ectodomain	130:157	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005)	130:253	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	1	14	from	isolate	219:225	arg1	subunit					164:170	HA1 subunit	160:170	HA1 subunit	160:170	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	10	15	theme	virus	1820:1824	arg1	infection					1826:1834	H5 avian influenza virus infection	1801:1834	H5 avian influenza virus infection	1801:1834	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	9	16	from	subtypes	1626:1633	arg1	antibodies					1589:1598	antibodies	1589:1598	antibodies from 15 other influenza A subtypes	1589:1633	No cross-reactivity to antibodies from 15 other influenza A subtypes was detected.
26040437	0	17	theme	Pathogenic	57:66	arg1	Virus					89:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	1	18	theme	hemagglutinin	134:146	arg1	ectodomain					148:157	The hemagglutinin ectodomain	130:157	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005)	130:253	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	1	18	theme	hemagglutinin	134:146	arg1	subunit					164:170	HA1 subunit	160:170	HA1 subunit	160:170	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	0	19	from	Characterization	15:30	arg1	Assay					123:127	a Serodiagnostic Assay	106:127	a Serodiagnostic Assay	106:127	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	0	20	theme	Avian	73:77	arg1	Virus					89:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	5	21	theme	HA1	1120:1122	arg1	secretion					1103:1111	efficient secretion	1093:1111	efficient secretion of the HA1	1093:1122	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	5	21	theme	HA1	1120:1122	arg1	level					1069:1073	a high level	1062:1073	a high level of expression	1062:1087	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	4	22	gly	glycosylated	873:884	arg1	proteins					827:834	the recombinant HA1 proteins	807:834	the recombinant HA1 proteins produced in insect cells	807:859	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	0	23	from	Expression	0:9	arg1	Assay					123:127	a Serodiagnostic Assay	106:127	a Serodiagnostic Assay	106:127	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	0	24	theme	Virus	89:93	arg1	Protein					39:45	HA1 Protein	35:45	HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use	35:101	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	5	25	theme	expression	1078:1087	arg1	secretion					1103:1111	efficient secretion	1093:1111	efficient secretion of the HA1	1093:1122	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	5	25	theme	expression	1078:1087	arg1	level					1069:1073	a high level	1062:1073	a high level of expression	1062:1087	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	2	26	from	N-terminus	431:440	arg1	peptide					416:422	a melittin signal peptide	398:422	a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus	398:490	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	5	27	theme	efficient	1093:1101	arg1	secretion					1103:1111	efficient secretion	1093:1111	efficient secretion of the HA1	1093:1122	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	7	28	theme	immunofluorescent	1315:1331	arg1	staining					1333:1340	indirect immunofluorescent staining	1306:1340	indirect immunofluorescent staining	1306:1340	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	0	29	theme	H5N1	68:71	arg1	Virus					89:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	2	30	theme	proteins	372:379	arg1	secretion					351:359	secretion	351:359	secretion	351:359	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	2	30	theme	proteins	372:379	arg1	glycosylation					333:345	glycosylation	333:345	glycosylation	333:345	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	2	30	theme	proteins	372:379	arg1	Biosynthesis					319:330	Biosynthesis	319:330	Biosynthesis	319:330	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	2	31	theme	melittin	400:407	arg1	peptide					416:422	a melittin signal peptide	398:422	a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus	398:490	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	3	32	theme	protein	604:610	arg1	precursor					548:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	3	32	theme	protein	604:610	arg1	form					588:591	a fully processed, mature form	562:591	a fully processed, mature form of the HA1 protein migrated around 52 kDa	562:633	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	8	33	theme	Recombinant	1398:1408	arg1	ELISA					1428:1432	Recombinant HA1 protein-based ELISA	1398:1432	Recombinant HA1 protein-based ELISA	1398:1432	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	10	34	theme	recombinant	1685:1695	arg1	ELISA					1707:1711	the newly developed recombinant HA1-based ELISA	1665:1711	the newly developed recombinant HA1-based ELISA	1665:1711	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	0	35	theme	HA1	35:37	arg1	Protein					39:45	HA1 Protein	35:45	HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use	35:101	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	9	36	theme	influenza	1614:1622	arg1	subtypes					1626:1633	15 other influenza A subtypes	1605:1633	15 other influenza A subtypes	1605:1633	No cross-reactivity to antibodies from 15 other influenza A subtypes was detected.
26040437	8	37	theme	protein-based	1414:1426	arg1	ELISA					1428:1432	Recombinant HA1 protein-based ELISA	1398:1432	Recombinant HA1 protein-based ELISA	1398:1432	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	1	38	theme	expression	300:309	arg1	vector					311:316	a baculovirus expression vector	286:316	a baculovirus expression vector	286:316	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	7	39	theme	surface	1263:1269	arg1	expression					1271:1280	the cell surface expression	1254:1280	the cell surface expression of rHA1	1254:1288	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	4	40	theme	F	772:772	arg1	Treatment					721:729	Treatment	721:729	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F)	721:783	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	5	41	theme	HA	985:986	arg1	sequence					996:1003	the HA natural sequence	981:1003	the HA natural sequence	981:1003	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	4	42	theme	PNGase	775:780	arg1	F					772:772	peptide-N-glycosidase F	750:772	peptide-N-glycosidase F (PNGase F)	750:783	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	4	42	theme	PNGase	775:780	arg1	F					782:782	PNGase F	775:782	PNGase F	775:782	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	2	43	with	proteins	372:379	arg1	peptide					416:422	a melittin signal peptide	398:422	a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus	398:490	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	2	43	with	proteins	372:379	arg1	natural					387:393	natural	387:393	natural	387:393	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	5	44	theme	sequence	996:1003	arg1	substitution					965:976	substitution	965:976	substitution of the HA natural sequence with the signal sequence from honeybee melittin	965:1051	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	4	45	link	N-linked	891:898	arg1	chains					921:926	N-linked oligosaccharide side chains	891:926	N-linked oligosaccharide side chains	891:926	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	10	46	theme	other	1743:1747	arg1	approaches					1760:1769	other diagnostic approaches	1743:1769	other diagnostic approaches	1743:1769	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	8	47	theme	rapid	1498:1502	arg1	detection					1504:1512	the rapid detection	1494:1512	the rapid detection of H5 subtype-specific antibodies in serum samples	1494:1563	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	9	48	theme	A	1624:1624	arg1	subtypes					1626:1633	15 other influenza A subtypes	1605:1633	15 other influenza A subtypes	1605:1633	No cross-reactivity to antibodies from 15 other influenza A subtypes was detected.
26040437	10	49	theme	influenza	1810:1818	arg1	virus					1820:1824	H5 avian influenza virus	1801:1824	H5 avian influenza virus infection	1801:1834	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	1	50	theme	HA1	160:162	arg1	ectodomain					148:157	The hemagglutinin ectodomain	130:157	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005)	130:253	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	1	50	theme	HA1	160:162	arg1	subunit					164:170	HA1 subunit	160:170	HA1 subunit	160:170	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	3	51	theme	40-kDa	526:531	arg1	precursor					548:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor	524:556	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	4	52	theme	recombinant	811:821	arg1	proteins					827:834	the recombinant HA1 proteins	807:834	the recombinant HA1 proteins produced in insect cells	807:859	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	0	53	theme	Serodiagnostic	108:121	arg1	Assay					123:127	a Serodiagnostic Assay	106:127	a Serodiagnostic Assay	106:127	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	10	54	theme	H5	1801:1802	arg1	virus					1820:1824	H5 avian influenza virus	1801:1824	H5 avian influenza virus infection	1801:1834	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	3	55	dep	processed	570:578	arg1	mature					581:586	mature	581:586	mature	581:586	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	10	56	theme	avian	1804:1808	arg1	virus					1820:1824	H5 avian influenza virus	1801:1824	H5 avian influenza virus infection	1801:1834	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	2	57	theme	insect	510:515	arg1	cells					517:521	insect cells	510:521	insect cells	510:521	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	5	58	with	substitution	965:976	arg1	sequence					1021:1028	the signal sequence	1010:1028	the signal sequence from honeybee melittin	1010:1051	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	3	59	theme	H5N1-specific	697:709	arg1	antibody					711:718	H5N1-specific antibody	697:718	H5N1-specific antibody	697:718	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	5	60	theme	high	1064:1067	arg1	level					1069:1073	a high level	1062:1073	a high level of expression	1062:1087	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	1	61	theme	avian	196:200	arg1	A/chicken/Vietnam/14/2005					228:252	A/chicken/Vietnam/14/2005	228:252	A/chicken/Vietnam/14/2005	228:252	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	1	61	theme	avian	196:200	arg1	isolate					219:225	avian influenza (HPAI) isolate	196:225	highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005)	178:253	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	4	62	theme	oligosaccharide	900:914	arg1	chains					921:926	N-linked oligosaccharide side chains	891:926	N-linked oligosaccharide side chains	891:926	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	6	63	theme	cell	1215:1218	arg1	supernatant					1228:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	10	64	theme	infection	1826:1834	arg1	detection					1788:1796	the specific detection	1775:1796	the specific detection of H5 avian influenza virus infection	1775:1834	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	2	65	from	C-terminus	481:490	arg1	tag					470:472	six-histidine (6xHis) tag	448:472	six-histidine (6xHis) tag at the C-terminus	448:490	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	6	66	theme	recombinant	1182:1192	arg1	supernatant					1228:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	5	67	theme	honeybee	1035:1042	arg1	melittin					1044:1051	honeybee melittin	1035:1051	honeybee melittin	1035:1051	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	7	68	theme	biological	1353:1362	arg1	activity					1364:1371	biological activity	1353:1371	biological activity	1353:1371	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	5	69	from	melittin	1044:1051	arg1	sequence					1021:1028	the signal sequence	1010:1028	the signal sequence from honeybee melittin	1010:1051	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	7	70	located	detected	1294:1301	arg2	expression					1271:1280	the cell surface expression	1254:1280	the cell surface expression of rHA1	1254:1288	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	7	70	located	detected	1294:1301	arg1	addition					1244:1251	addition	1244:1251	addition	1244:1251	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	3	71	theme	processed	570:578	arg1	form					588:591	a fully processed, mature form	562:591	a fully processed, mature form of the HA1 protein migrated around 52 kDa	562:633	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	6	72	theme	protein	1156:1162	arg1	yield					1132:1136	A high yield	1125:1136	A high yield	1125:1136	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	6	72	theme	protein	1156:1162	arg1	37 μg/ml					1139:1146	37 μg/ml	1139:1146	37 μg/ml	1139:1146	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	0	73	theme	Influenza	79:87	arg1	Virus					89:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Highly Pathogenic H5N1 Avian Influenza Virus	50:93	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	2	74	theme	6xHis	463:467	arg1	tag					470:472	six-histidine (6xHis) tag	448:472	six-histidine (6xHis) tag at the C-terminus	448:490	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	8	75	theme	H5	1517:1518	arg1	antibodies					1537:1546	H5 subtype-specific antibodies	1517:1546	H5 subtype-specific antibodies	1517:1546	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	8	76	theme	antibodies	1537:1546	arg1	detection					1504:1512	the rapid detection	1494:1512	the rapid detection of H5 subtype-specific antibodies in serum samples	1494:1563	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	7	77	theme	indirect	1306:1313	arg1	staining					1333:1340	indirect immunofluorescent staining	1306:1340	indirect immunofluorescent staining	1306:1340	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	8	78	theme	serum	1551:1555	arg1	samples					1557:1563	serum samples	1551:1563	serum samples	1551:1563	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	4	79	theme	tunicamycin	734:744	arg1	Treatment					721:729	Treatment	721:729	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F)	721:783	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	8	80	theme	subtype-specific	1520:1535	arg1	antibodies					1537:1546	H5 subtype-specific antibodies	1517:1546	H5 subtype-specific antibodies	1517:1546	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	2	81	theme	HA1	368:370	arg1	proteins					372:379	the HA1 proteins	364:379	the HA1 proteins	364:379	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	8	82	from	detection	1504:1512	arg1	samples					1557:1563	serum samples	1551:1563	serum samples	1551:1563	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	5	83	theme	Time-course	929:939	arg1	experiments					941:951	Time-course experiments	929:951	Time-course experiments	929:951	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	6	84	theme	culture	1220:1226	arg1	supernatant					1228:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	recombinant baculovirus-infected cell culture supernatant	1182:1238	A high yield, 37 μg/ml, of HA1 protein was obtained from recombinant baculovirus-infected cell culture supernatant.
26040437	7	85	theme	rHA1	1285:1288	arg1	expression					1271:1280	the cell surface expression	1254:1280	the cell surface expression of rHA1	1254:1288	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	2	86	theme	signal	409:414	arg1	peptide					416:422	a melittin signal peptide	398:422	a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus	398:490	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	3	87	theme	HA1	600:602	arg1	protein					604:610	the HA1 protein	596:610	the HA1 protein migrated around 52 kDa	596:633	A 40-kDa unglycosylated precursor and a fully processed, mature form of the HA1 protein migrated around 52 kDa were detected by SDS-PAGE and confirmed by Western blot using H5N1-specific antibody.
26040437	10	88	theme	HA1-based	1697:1705	arg1	ELISA					1707:1711	the newly developed recombinant HA1-based ELISA	1665:1711	the newly developed recombinant HA1-based ELISA	1665:1711	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	0	89	theme	Protein	39:45	arg1	Characterization					15:30	Characterization	15:30	Characterization	15:30	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	0	89	theme	Protein	39:45	arg1	Expression					0:9	Expression	0:9	Expression	0:9	Expression and Characterization of HA1 Protein of Highly Pathogenic H5N1 Avian Influenza Virus for Use in a Serodiagnostic Assay.
26040437	9	90	theme	other	1608:1612	arg1	subtypes					1626:1633	15 other influenza A subtypes	1605:1633	15 other influenza A subtypes	1605:1633	No cross-reactivity to antibodies from 15 other influenza A subtypes was detected.
26040437	2	91	theme	six-histidine	448:460	arg1	tag					470:472	six-histidine (6xHis) tag	448:472	six-histidine (6xHis) tag at the C-terminus	448:490	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	10	92	theme	developed	1675:1683	arg1	ELISA					1707:1711	the newly developed recombinant HA1-based ELISA	1665:1711	the newly developed recombinant HA1-based ELISA	1665:1711	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
26040437	1	93	theme	baculovirus	288:298	arg1	vector					311:316	a baculovirus expression vector	286:316	a baculovirus expression vector	286:316	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	5	94	theme	signal	1014:1019	arg1	sequence					1021:1028	the signal sequence	1010:1028	the signal sequence from honeybee melittin	1010:1051	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	7	95	theme	cell	1258:1261	arg1	expression					1271:1280	the cell surface expression	1254:1280	the cell surface expression of rHA1	1254:1288	In addition, the cell surface expression of rHA1 was detected by indirect immunofluorescent staining and showed biological activity on hemadsorption assays.
26040437	2	96	gly	glycosylation	333:345	arg1	cells					517:521	insect cells	510:521	insect cells	510:521	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	2	96	gly	glycosylation	333:345	arg1	proteins					372:379	the HA1 proteins	364:379	the HA1 proteins	364:379	Biosynthesis, glycosylation and secretion of the HA1 proteins, with natural or a melittin signal peptide at the N-terminus and a six-histidine (6xHis) tag at the C-terminus, were examined in insect cells.
26040437	8	97	theme	HA1	1410:1412	arg1	ELISA					1428:1432	Recombinant HA1 protein-based ELISA	1398:1432	Recombinant HA1 protein-based ELISA	1398:1432	Recombinant HA1 protein-based ELISA was evaluated and appeared to be sensitive and specific for the rapid detection of H5 subtype-specific antibodies in serum samples.
26040437	4	98	theme	peptide-N-glycosidase	750:770	arg1	F					772:772	peptide-N-glycosidase F	750:772	peptide-N-glycosidase F (PNGase F)	750:783	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	4	98	theme	peptide-N-glycosidase	750:770	arg1	F					782:782	PNGase F	775:782	PNGase F	775:782	Treatment of tunicamycin and peptide-N-glycosidase F (PNGase F) further revealed that the recombinant HA1 proteins produced in insect cells were indeed glycosylated with N-linked oligosaccharide side chains.
26040437	1	99	theme	HPAI	213:216	arg1	A/chicken/Vietnam/14/2005					228:252	A/chicken/Vietnam/14/2005	228:252	A/chicken/Vietnam/14/2005	228:252	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	1	99	theme	HPAI	213:216	arg1	isolate					219:225	avian influenza (HPAI) isolate	196:225	highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005)	178:253	The hemagglutinin ectodomain (HA1 subunit) from highly pathogenic avian influenza (HPAI) isolate (A/chicken/Vietnam/14/2005) was cloned and expressed using a baculovirus expression vector.
26040437	5	100	theme	natural	988:994	arg1	sequence					996:1003	the HA natural sequence	981:1003	the HA natural sequence	981:1003	Time-course experiments showed that substitution of the HA natural sequence with the signal sequence from honeybee melittin promoted a high level of expression and efficient secretion of the HA1.
26040437	10	101	theme	diagnostic	1749:1758	arg1	approaches					1760:1769	other diagnostic approaches	1743:1769	other diagnostic approaches	1743:1769	Taken together, the newly developed recombinant HA1-based ELISA could offer an alternative to other diagnostic approaches for the specific detection of H5 avian influenza virus infection.
31800099	7	0	theme	plasma	1180:1185	arg1	HDL					1187:1189	plasma HDL	1180:1189	plasma HDL	1180:1189	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	4	1	theme	lipoprotein	725:735	arg1	HDL-c					750:754	HDL-c	750:754	HDL-c	750:754	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	4	1	theme	lipoprotein	725:735	arg1	cholesterol					737:747	non-high density lipoprotein cholesterol	708:747	non-high density lipoprotein cholesterol (HDL-c)	708:755	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	5	2	theme	matched	928:934	arg1	controls					936:943	matched controls	928:943	matched controls	928:943	Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls.
31800099	4	3	theme	density	717:723	arg1	lipoprotein					725:735	non-high density lipoprotein	708:735	non-high density lipoprotein cholesterol (HDL-c)	708:755	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	2	4	with	patients	303:310	arg1	B4GALT1-CDG					317:327	B4GALT1-CDG	317:327	B4GALT1-CDG	317:327	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	3	5	theme	gender-matched	626:639	arg1	controls					650:657	11 age- and gender-matched, healthy controls	614:657	controls	650:657	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	8	6	contain	have	1226:1229	arg1	Patients					1200:1207	Patients	1200:1207	Patients with B4GALT1-CDG	1200:1224	Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
31800099	8	6	contain	have	1226:1229	arg2	particles					1241:1249	large HDL particles	1231:1249	large HDL particles	1231:1249	Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
31800099	3	7	theme	known	564:568	arg1	patients					582:589	three known B4GALT1-CDG patients	558:589	three known B4GALT1-CDG patients	558:589	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	6	8	theme	lipoprotein	1021:1031	arg1	homeostasis					1033:1043	human lipoprotein homeostasis	1015:1043	human lipoprotein homeostasis	1015:1043	Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis.
31800099	4	9	theme	total	761:765	arg1	cholesterol					767:777	total cholesterol	761:777	total cholesterol to HDL-c ratio	761:792	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	2	10	from	mutation	342:349	arg1	B4GALT1					354:360	B4GALT1	354:360	B4GALT1 with defective N-linked glycosylation	354:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	4	11	theme	HDL-c	782:786	arg1	ratio					788:792	HDL-c ratio	782:792	HDL-c ratio	782:792	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	6	12	theme	human	1015:1019	arg1	homeostasis					1033:1043	human lipoprotein homeostasis	1015:1043	human lipoprotein homeostasis	1015:1043	Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis.
31800099	8	13	theme	large	1231:1235	arg1	particles					1241:1249	large HDL particles	1231:1249	large HDL particles	1231:1249	Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
31800099	5	14	gly	hypoglycosylated	859:874	arg1	CETP					850:853	Plasma CETP	843:853	Plasma CETP	843:853	Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls.
31800099	2	15	theme	plasma	286:291	arg1	lipids					293:298	plasma lipids	286:298	plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation	286:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	5	16	theme	B4GALT1-CDG	895:905	arg1	patients					907:914	B4GALT1-CDG patients	895:914	B4GALT1-CDG patients	895:914	Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls.
31800099	3	17	theme	transfer	445:452	arg1	CETP					463:466	CETP	463:466	CETP	463:466	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	3	17	theme	transfer	445:452	arg1	protein					454:460	cholesteryl ester transfer protein	427:460	cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot	427:535	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	6	18	theme	glycosylation	998:1010	arg1	role					982:985	the role	978:985	the role of protein glycosylation in human lipoprotein homeostasis	978:1043	Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis.
31800099	6	19	gly	glycosylation	998:1010	arg1	lipoprotein					1021:1031	human lipoprotein homeostasis	1015:1043	human lipoprotein homeostasis	1015:1043	Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis.
31800099	3	20	theme	CETP	541:544	arg1	activity					546:553	CETP activity	541:553	CETP activity	541:553	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	7	21	located	found	1087:1091	arg2	CETP					1082:1085	The hypogalactosylated, hypo-active CETP	1046:1085	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG	1046:1120	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	7	21	located	found	1087:1091	arg1	patients					1096:1103	patients	1096:1103	patients with B4GALT1-CDG	1096:1120	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	3	22	theme	protein	454:460	arg1	glyco-isoforms					469:482	cholesteryl ester transfer protein (CETP) glyco-isoforms	427:482	cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot	427:535	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	0	23	theme	CETP	8:11	arg1	glycosylation					13:25	CETP glycosylation	8:25	CETP glycosylation	8:25	Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations.
31800099	8	24	theme	HDL	1237:1239	arg1	particles					1241:1249	large HDL particles	1231:1249	large HDL particles	1231:1249	Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
31800099	4	25	theme	B4GALT1-CDG	660:670	arg1	patients					672:679	B4GALT1-CDG patients	660:679	B4GALT1-CDG patients	660:679	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	3	26	theme	B4GALT1-CDG	570:580	arg1	patients					582:589	three known B4GALT1-CDG patients	558:589	three known B4GALT1-CDG patients	558:589	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	3	27	theme	cholesteryl	427:437	arg1	CETP					463:466	CETP	463:466	CETP	463:466	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	3	27	theme	cholesteryl	427:437	arg1	protein					454:460	cholesteryl ester transfer protein	427:460	cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot	427:535	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	2	28	gly	glycosylation	269:281	arg1	plasma					286:291	plasma lipids	286:298	plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation	286:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	2	29	gly	glycosylation	386:398	arg1	B4GALT1					354:360	B4GALT1	354:360	B4GALT1 with defective N-linked glycosylation	354:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	7	30	theme	protein	1142:1148	arg1	galactosylation					1150:1164	protein galactosylation	1142:1164	protein galactosylation	1142:1164	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	2	31	theme	N-linked	377:384	arg1	glycosylation					386:398	defective N-linked glycosylation	367:398	defective N-linked glycosylation	367:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	5	32	theme	Plasma	843:848	arg1	CETP					850:853	Plasma CETP	843:853	Plasma CETP	843:853	Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls.
31800099	4	33	theme	HDL	828:830	arg1	particles					832:840	larger HDL particles	821:840	larger HDL particles	821:840	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	2	34	from	effects	248:254	arg1	lipids					293:298	plasma lipids	286:298	plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation	286:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	5	35	from	patients	907:914	arg1	active					885:890	active	885:890	active	885:890	Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls.
31800099	6	36	theme	protein	990:996	arg1	glycosylation					998:1010	protein glycosylation	990:1010	protein glycosylation	990:1010	Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis.
31800099	3	37	with	lipids	419:424	arg1	isoelectric					489:499	isoelectric	489:499	isoelectric	489:499	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	1	38	theme	protein	105:111	arg1	glycosylation					113:125	protein glycosylation	105:125	protein glycosylation	105:125	The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent.
31800099	3	39	theme	western	524:530	arg1	blot					532:535	a western blot	522:535	a western blot	522:535	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	8	40	theme	hypogalactosylated	1267:1284	arg1	CETP					1299:1302	hypogalactosylated, hypo-active CETP	1267:1302	hypogalactosylated, hypo-active CETP	1267:1302	Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
31800099	7	41	dep	hypogalactosylated	1050:1067	arg1	hypo-active					1070:1080	hypo-active	1070:1080	hypo-active	1070:1080	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	8	42	dep	hypogalactosylated	1267:1284	arg1	hypo-active					1287:1297	hypo-active	1287:1297	hypo-active	1287:1297	Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
31800099	2	43	link	N-linked	377:384	arg1	glycosylation					386:398	defective N-linked glycosylation	367:398	defective N-linked glycosylation	367:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	3	44	theme	ester	439:443	arg1	CETP					463:466	CETP	463:466	CETP	463:466	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	3	44	theme	ester	439:443	arg1	protein					454:460	cholesteryl ester transfer protein	427:460	cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot	427:535	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	4	45	theme	non-high	708:715	arg1	lipoprotein					725:735	non-high density lipoprotein	708:735	non-high density lipoprotein cholesterol (HDL-c)	708:755	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	3	46	with	glyco-isoforms	469:482	arg1	isoelectric					489:499	isoelectric	489:499	isoelectric	489:499	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	7	47	with	patients	1096:1103	arg1	B4GALT1-CDG					1110:1120	B4GALT1-CDG	1110:1120	B4GALT1-CDG	1110:1120	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	3	48	with	activity	546:553	arg1	isoelectric					489:499	isoelectric	489:499	isoelectric	489:499	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	3	49	theme	healthy	642:648	arg1	controls					650:657	11 age- and gender-matched, healthy controls	614:657	controls	650:657	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	0	50	gly	glycosylation	13:25	arg1	patients					43:50	patients	43:50	patients with homozygous B4GALT1 mutations	43:84	Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations.
31800099	1	51	theme	glycosylation	113:125	arg1	importance					91:100	The importance	87:100	The importance of protein glycosylation in regulating lipid metabolism	87:156	The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent.
31800099	3	52	theme	plasma	412:417	arg1	lipids					419:424	plasma lipids	412:424	plasma lipids	412:424	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	2	53	with	B4GALT1	354:360	arg1	glycosylation					386:398	defective N-linked glycosylation	367:398	defective N-linked glycosylation	367:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	7	54	theme	galactosylation	1150:1164	arg1	role					1134:1137	a role	1132:1137	a role of protein galactosylation in regulating plasma HDL and LDL	1132:1197	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	4	55	theme	larger	821:826	arg1	particles					832:840	larger HDL particles	821:840	larger HDL particles	821:840	B4GALT1-CDG patients have significantly lowered non-high density lipoprotein cholesterol (HDL-c) and total cholesterol to HDL-c ratio compared with controls and larger HDL particles.
31800099	6	56	from	role	982:985	arg1	homeostasis					1033:1043	human lipoprotein homeostasis	1015:1043	human lipoprotein homeostasis	1015:1043	Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis.
31800099	2	57	theme	glycosylation	269:281	arg1	effects					248:254	the effects	244:254	the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation	244:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	7	58	theme	hypogalactosylated	1050:1067	arg1	CETP					1082:1085	The hypogalactosylated, hypo-active CETP	1046:1085	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG	1046:1120	The hypogalactosylated, hypo-active CETP found in patients with B4GALT1-CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL.
31800099	2	59	theme	defective	259:267	arg1	glycosylation					269:281	defective glycosylation	259:281	defective glycosylation	259:281	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	8	60	with	Patients	1200:1207	arg1	B4GALT1-CDG					1214:1224	B4GALT1-CDG	1214:1224	B4GALT1-CDG	1214:1224	Patients with B4GALT1-CDG have large HDL particles probably due to hypogalactosylated, hypo-active CETP.
31800099	1	61	theme	lipid	141:145	arg1	metabolism					147:156	lipid metabolism	141:156	lipid metabolism	141:156	The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent.
31800099	0	62	theme	B4GALT1	68:74	arg1	mutations					76:84	homozygous B4GALT1 mutations	57:84	homozygous B4GALT1 mutations	57:84	Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations.
31800099	3	63	theme	11	614:615	arg1	age-					617:620	age-	617:620	age-	617:620	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	0	64	with	patients	43:50	arg1	mutations					76:84	homozygous B4GALT1 mutations	57:84	homozygous B4GALT1 mutations	57:84	Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations.
31800099	2	65	theme	defective	367:375	arg1	glycosylation					386:398	defective N-linked glycosylation	367:398	defective N-linked glycosylation	367:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	2	66	from	lipids	293:298	arg1	patients					303:310	patients	303:310	patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation	303:398	We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1-CDG, caused by a mutation in B4GALT1 with defective N-linked glycosylation.
31800099	0	67	theme	homozygous	57:66	arg1	mutations					76:84	homozygous B4GALT1 mutations	57:84	homozygous B4GALT1 mutations	57:84	Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations.
31800099	3	68	theme	age-	617:620	arg1	controls					650:657	11 age- and gender-matched, healthy controls	614:657	controls	650:657	We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco-isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1-CDG patients and compared them with 11 age- and gender-matched, healthy controls.
31800099	5	69	from	active	885:890	arg1	patients					907:914	B4GALT1-CDG patients	895:914	B4GALT1-CDG patients	895:914	Plasma CETP was hypoglycosylated and less active in B4GALT1-CDG patients compared to matched controls.
29281684	9	0	theme	immune	1727:1732	arg1	responses					1734:1742	TLR4 dependent innate immune responses	1705:1742	TLR4 dependent innate immune responses targeting different C. albicans strains	1705:1782	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	7	1	attach	derived	1326:1332	arg1	B					1366:1366	serotype B	1357:1366	serotype B	1357:1366	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	7	1	attach	derived	1326:1332	arg2	CMP					1322:1324	CMP	1322:1324	CMP derived from parental A9 (both serotype B)	1322:1367	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	7	1	attach	derived	1326:1332	arg1	A9					1348:1349	parental A9	1339:1349	parental A9 (both serotype B)	1339:1367	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	2	2	theme	dose-dependent	530:543	arg1	response					550:557	a dose-dependent SEAP response	528:557	a dose-dependent SEAP response to both LPS and CMP	528:577	TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40-50 μg/mL of CMP.
29281684	6	3	theme	limited	1105:1111	arg1	effect					1113:1118	limited effect	1105:1118	limited effect	1105:1118	Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses.
29281684	7	4	dep	B	1366:1366	arg1	both					1352:1355	both	1352:1355	both	1352:1355	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	7	5	theme	≤	1290:1290	arg1	p					1288:1288	p ≤ 0.005	1288:1296	p ≤ 0.005	1288:1296	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	6	6	theme	CMP	1131:1133	arg1	responses					1135:1143	LPS and CMP responses	1123:1143	LPS and CMP responses	1123:1143	Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses.
29281684	1	7	theme	reporter	388:395	arg1	cells					397:401	These TLR4 reporter cells	377:401	These TLR4 reporter cells	377:401	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	0	8	theme	Candida	0:6	arg1	mannoproteins					25:37	Candida albicans-derived mannoproteins	0:37	Candida albicans-derived mannoproteins	0:37	Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14.
29281684	4	9	theme	Null	776:779	arg1	cells					781:785	HEK293 Null cells	769:785	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter	769:836	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter failed to respond to LPS or CMP, but produced SEAP when activated with TNFα.
29281684	3	10	theme	B	684:684	arg1	resin					686:690	polymyxin B resin	674:690	polymyxin B resin	674:690	Incubation on polymyxin B resin had no effect on CMP's ligand activity, but neutralized LPS-spiked controls.
29281684	6	11	theme	LPS	1123:1125	arg1	responses					1135:1143	LPS and CMP responses	1123:1143	LPS and CMP responses	1123:1143	Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses.
29281684	3	12	from	Incubation	660:669	arg1	resin					686:690	polymyxin B resin	674:690	polymyxin B resin	674:690	Incubation on polymyxin B resin had no effect on CMP's ligand activity, but neutralized LPS-spiked controls.
29281684	1	13	theme	human	339:343	arg1	TLR4					345:348	human TLR4	339:348	human TLR4	339:348	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	5	14	theme	IL-8	982:985	arg1	transcription					965:977	transcription	965:977	transcription of IL-8, TNFα, and COX-2 genes	965:1008	Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes.
29281684	7	15	theme	N-linked	1243:1250	arg1	glycans					1252:1258	N-linked glycans	1243:1258	N-linked glycans	1243:1258	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	4	16	theme	SEAP	824:827	arg1	reporter					829:836	the same SEAP reporter	815:836	the same SEAP reporter	815:836	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter failed to respond to LPS or CMP, but produced SEAP when activated with TNFα.
29281684	2	17	theme	TLR4-reporter	498:510	arg1	cells					512:516	TLR4-reporter cells	498:516	TLR4-reporter cells	498:516	TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40-50 μg/mL of CMP.
29281684	3	18	theme	ligand	715:720	arg1	activity					722:729	CMP's ligand activity	709:729	CMP's ligand activity	709:729	Incubation on polymyxin B resin had no effect on CMP's ligand activity, but neutralized LPS-spiked controls.
29281684	1	19	theme	C.	126:127	arg1	20A					138:140	C. albicans 20A	126:140	soluble C. albicans 20A (serotype A) mannoprotein (CMP)	118:172	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	19	theme	C.	126:127	arg1	A					152:152	serotype A	143:152	serotype A	143:152	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	9	20	theme	CMPs	1587:1590	arg1	application					1621:1631	their application	1615:1631	their application in this model	1615:1645	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	9	20	theme	CMPs	1587:1590	arg1	characterizations					1566:1582	Future characterizations	1559:1582	Future characterizations of CMPs from other sources	1559:1609	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	5	21	theme	genes	1004:1008	arg1	transcription					965:977	transcription	965:977	transcription of IL-8, TNFα, and COX-2 genes	965:1008	Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes.
29281684	7	22	dep	greater	1279:1285	arg1	p					1288:1288	p ≤ 0.005	1288:1296	p ≤ 0.005	1288:1296	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	9	23	theme	other	1597:1601	arg1	sources					1603:1609	other sources	1597:1609	other sources	1597:1609	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	1	24	theme	serotype	143:150	arg1	20A					138:140	C. albicans 20A	126:140	soluble C. albicans 20A (serotype A) mannoprotein (CMP)	118:172	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	24	theme	serotype	143:150	arg1	A					152:152	serotype A	143:152	serotype A	143:152	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	2	25	theme	wherein	580:586	arg1	activation					593:602	wherein peak activation	580:602	wherein peak activation	580:602	TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40-50 μg/mL of CMP.
29281684	5	26	theme	TNFα	988:991	arg1	transcription					965:977	transcription	965:977	transcription of IL-8, TNFα, and COX-2 genes	965:1008	Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes.
29281684	1	27	dep	ability	107:113	arg1	serve					177:181	serve	177:181	to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors	174:246	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	9	28	theme	further	1659:1665	arg1	insight					1667:1673	further insight	1659:1673	further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains	1659:1782	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	7	29	from	phosphomannosylations	1218:1238	arg1	glycans					1252:1258	N-linked glycans	1243:1258	N-linked glycans	1243:1258	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	2	30	with	stimulation	623:633	arg1	μg/mL					646:650	40-50 μg/mL	640:650	40-50 μg/mL of CMP	640:657	TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40-50 μg/mL of CMP.
29281684	6	31	theme	TNFα-dependent	1047:1060	arg1	responses					1068:1076	TNFα-dependent NF-κB responses	1047:1076	TNFα-dependent NF-κB responses	1047:1076	Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses.
29281684	9	32	from	application	1621:1631	arg1	sources					1603:1609	other sources	1597:1609	other sources	1597:1609	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	9	32	from	application	1621:1631	arg1	model					1641:1645	this model	1636:1645	this model	1636:1645	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	7	33	link	N-linked	1243:1250	arg1	glycans					1252:1258	N-linked glycans	1243:1258	N-linked glycans	1243:1258	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	8	34	theme	engineered	1394:1403	arg1	cells					1411:1415	engineered human cells	1394:1415	engineered human cells expressing TLR4, MD2 and CD14	1394:1445	These data confirm that engineered human cells expressing TLR4, MD2 and CD14 can respond to CMP with NF-κB activation and the response can be influenced by variations in CMP-mannosylation.
29281684	5	35	theme	Reporter	915:922	arg1	responses					935:943	Reporter cell NF-κB responses	915:943	Reporter cell NF-κB responses	915:943	Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes.
29281684	8	36	from	variations	1526:1535	arg1	CMP-mannosylation					1540:1556	CMP-mannosylation	1540:1556	CMP-mannosylation	1540:1556	These data confirm that engineered human cells expressing TLR4, MD2 and CD14 can respond to CMP with NF-κB activation and the response can be influenced by variations in CMP-mannosylation.
29281684	1	37	theme	NF-κB-dependent	419:433	arg1	SEAP					477:480	SEAP	477:480	SEAP	477:480	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	37	theme	NF-κB-dependent	419:433	arg1	phosphatase					464:474	an NF-κB-dependent, secreted embryonic alkaline phosphatase	416:474	phosphatase	464:474	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	4	38	dep	cells	781:785	arg1	lacking					787:793	lacking	787:793	lacking TLR4	787:798	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter failed to respond to LPS or CMP, but produced SEAP when activated with TNFα.
29281684	4	38	dep	cells	781:785	arg1	possessing					804:813	possessing	804:813	possessing the same SEAP reporter	804:836	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter failed to respond to LPS or CMP, but produced SEAP when activated with TNFα.
29281684	7	39	theme	serotype	1357:1364	arg1	B					1366:1366	serotype B	1357:1366	serotype B	1357:1366	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	7	39	theme	serotype	1357:1364	arg1	A9					1348:1349	parental A9	1339:1349	parental A9 (both serotype B)	1339:1367	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	5	40	theme	NF-κB	929:933	arg1	responses					935:943	Reporter cell NF-κB responses	915:943	Reporter cell NF-κB responses	915:943	Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes.
29281684	1	41	theme	secreted	436:443	arg1	SEAP					477:480	SEAP	477:480	SEAP	477:480	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	41	theme	secreted	436:443	arg1	phosphatase					464:474	an NF-κB-dependent, secreted embryonic alkaline phosphatase	416:474	phosphatase	464:474	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	8	42	theme	NF-κB	1471:1475	arg1	activation					1477:1486	NF-κB activation	1471:1486	NF-κB activation	1471:1486	These data confirm that engineered human cells expressing TLR4, MD2 and CD14 can respond to CMP with NF-κB activation and the response can be influenced by variations in CMP-mannosylation.
29281684	7	43	theme	SEAP	1146:1149	arg1	production					1151:1160	SEAP production	1146:1160	SEAP production	1146:1160	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	1	44	theme	alkaline	455:462	arg1	SEAP					477:480	SEAP	477:480	SEAP	477:480	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	44	theme	alkaline	455:462	arg1	phosphatase					464:474	an NF-κB-dependent, secreted embryonic alkaline phosphatase	416:474	phosphatase	464:474	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	7	45	theme	parental	1339:1346	arg1	B					1366:1366	serotype B	1357:1366	serotype B	1357:1366	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	7	45	theme	parental	1339:1346	arg1	A9					1348:1349	parental A9	1339:1349	parental A9 (both serotype B)	1339:1367	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	9	46	theme	innate	1720:1725	arg1	responses					1734:1742	TLR4 dependent innate immune responses	1705:1742	TLR4 dependent innate immune responses targeting different C. albicans strains	1705:1782	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	1	47	dep	TLR4	345:348	arg1	express					408:414	express	408:414	express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	408:495	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	48	theme	toll-like	199:207	arg1	receptor					209:216	toll-like receptor 4	199:218	toll-like receptor 4 (TLR4)	199:225	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	48	theme	toll-like	199:207	arg1	TLR4					221:224	TLR4	221:224	TLR4	221:224	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	2	49	theme	SEAP	545:548	arg1	response					550:557	a dose-dependent SEAP response	528:557	a dose-dependent SEAP response to both LPS and CMP	528:577	TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40-50 μg/mL of CMP.
29281684	0	50	link	albicans-derived	8:23	arg1	mannoproteins					25:37	Candida albicans-derived mannoproteins	0:37	Candida albicans-derived mannoproteins	0:37	Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14.
29281684	6	51	theme	NF-κB	1062:1066	arg1	responses					1068:1076	TNFα-dependent NF-κB responses	1047:1076	TNFα-dependent NF-κB responses	1047:1076	Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses.
29281684	9	52	theme	different	1754:1762	arg1	strains					1776:1782	different C. albicans strains	1754:1782	different C. albicans strains	1754:1782	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	1	53	theme	TLR4	383:386	arg1	cells					397:401	These TLR4 reporter cells	377:401	These TLR4 reporter cells	377:401	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	0	54	theme	reporter	57:64	arg1	cells					66:70	reporter cells	57:70	reporter cells expressing TLR4, MD2 and CD14	57:100	Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14.
29281684	7	55	theme	SEAP	1304:1307	arg1	responses					1309:1317	SEAP responses	1304:1317	SEAP responses to CMP derived from parental A9 (both serotype B)	1304:1367	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	9	56	theme	albicans	1767:1774	arg1	strains					1776:1782	different C. albicans strains	1754:1782	different C. albicans strains	1754:1782	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	1	57	theme	mannoprotein	155:166	arg1	ability					107:113	The ability	103:113	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors	103:246	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	4	58	theme	HEK293	769:774	arg1	cells					781:785	HEK293 Null cells	769:785	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter	769:836	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter failed to respond to LPS or CMP, but produced SEAP when activated with TNFα.
29281684	7	59	from	production	1151:1160	arg1	response					1165:1172	response	1165:1172	response to C. albicans A9 mnn4Δ mutant CMP	1165:1207	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	3	60	theme	polymyxin	674:682	arg1	resin					686:690	polymyxin B resin	674:690	polymyxin B resin	674:690	Incubation on polymyxin B resin had no effect on CMP's ligand activity, but neutralized LPS-spiked controls.
29281684	9	61	theme	Future	1559:1564	arg1	characterizations					1566:1582	Future characterizations	1559:1582	Future characterizations of CMPs from other sources	1559:1609	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	1	62	theme	soluble	118:124	arg1	mannoprotein					155:166	soluble C. albicans 20A (serotype A) mannoprotein	118:166	soluble C. albicans 20A (serotype A) mannoprotein (CMP)	118:172	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	62	theme	soluble	118:124	arg1	CMP					169:171	CMP	169:171	CMP	169:171	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	9	63	from	characterizations	1566:1582	arg1	sources					1603:1609	other sources	1597:1609	other sources	1597:1609	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	9	63	from	characterizations	1566:1582	arg1	model					1641:1645	this model	1636:1645	this model	1636:1645	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	4	64	theme	same	819:822	arg1	reporter					829:836	the same SEAP reporter	815:836	the same SEAP reporter	815:836	HEK293 Null cells lacking TLR4 and possessing the same SEAP reporter failed to respond to LPS or CMP, but produced SEAP when activated with TNFα.
29281684	2	65	theme	CMP	655:657	arg1	μg/mL					646:650	40-50 μg/mL	640:650	40-50 μg/mL of CMP	640:657	TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40-50 μg/mL of CMP.
29281684	1	66	theme	available	280:288	arg1	cells					320:324	commercially available and stably-transfected HEK293 cells	267:324	commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	267:495	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	67	theme	HEK293	313:318	arg1	cells					320:324	commercially available and stably-transfected HEK293 cells	267:324	commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	267:495	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	2	68	theme	peak	588:591	arg1	activation					593:602	wherein peak activation	580:602	wherein peak activation	580:602	TLR4-reporter cells exhibited a dose-dependent SEAP response to both LPS and CMP, wherein peak activation was achieved after stimulation with 40-50 μg/mL of CMP.
29281684	3	69	theme	LPS-spiked	748:757	arg1	controls					759:766	LPS-spiked controls	748:766	LPS-spiked controls	748:766	Incubation on polymyxin B resin had no effect on CMP's ligand activity, but neutralized LPS-spiked controls.
29281684	1	70	theme	stably-transfected	294:311	arg1	cells					320:324	commercially available and stably-transfected HEK293 cells	267:324	commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	267:495	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	71	dep	C.	126:127	arg1	albicans					129:136	albicans	129:136	albicans	129:136	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	3	72	contain	had	692:694	arg2	effect					699:704	no effect	696:704	no effect	696:704	Incubation on polymyxin B resin had no effect on CMP's ligand activity, but neutralized LPS-spiked controls.
29281684	3	72	contain	had	692:694	arg1	Incubation					660:669	Incubation	660:669	Incubation on polymyxin B resin	660:690	Incubation on polymyxin B resin had no effect on CMP's ligand activity, but neutralized LPS-spiked controls.
29281684	7	73	theme	mutant	1198:1203	arg1	CMP					1205:1207	mutant CMP	1198:1207	mutant CMP	1198:1207	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	1	74	theme	reporter	483:490	arg1	gene					492:495	an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	416:495	an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	416:495	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	0	75	theme	albicans-derived	8:23	arg1	mannoproteins					25:37	Candida albicans-derived mannoproteins	0:37	Candida albicans-derived mannoproteins	0:37	Candida albicans-derived mannoproteins activate NF-κB in reporter cells expressing TLR4, MD2 and CD14.
29281684	5	76	theme	COX-2	998:1002	arg1	genes					1004:1008	COX-2 genes	998:1008	COX-2 genes	998:1008	Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes.
29281684	6	77	contain	had	1101:1103	arg2	effect					1113:1118	limited effect	1105:1118	limited effect	1105:1118	Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses.
29281684	6	77	contain	had	1101:1103	arg1	indomethacin					1088:1099	indomethacin	1088:1099	indomethacin	1088:1099	Celecoxib inhibited LPS-, CMP-, and TNFα-dependent NF-κB responses; whereas, indomethacin had limited effect on LPS and CMP responses.
29281684	7	78	theme	C.	1177:1178	arg1	A9					1189:1190	C. albicans A9	1177:1190	C. albicans A9 mnn4Δ mutant CMP	1177:1207	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	8	79	theme	human	1405:1409	arg1	cells					1411:1415	engineered human cells	1394:1415	engineered human cells expressing TLR4, MD2 and CD14	1394:1445	These data confirm that engineered human cells expressing TLR4, MD2 and CD14 can respond to CMP with NF-κB activation and the response can be influenced by variations in CMP-mannosylation.
29281684	5	80	theme	cell	924:927	arg1	responses					935:943	Reporter cell NF-κB responses	915:943	Reporter cell NF-κB responses	915:943	Reporter cell NF-κB responses were accompanied by transcription of IL-8, TNFα, and COX-2 genes.
29281684	1	81	theme	20A	138:140	arg1	mannoprotein					155:166	soluble C. albicans 20A (serotype A) mannoprotein	118:166	soluble C. albicans 20A (serotype A) mannoprotein (CMP)	118:172	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	81	theme	20A	138:140	arg1	CMP					169:171	CMP	169:171	CMP	169:171	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	9	82	from	sources	1603:1609	arg1	application					1621:1631	their application	1615:1631	their application in this model	1615:1645	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	9	82	from	sources	1603:1609	arg1	CMPs					1587:1590	CMPs	1587:1590	CMPs from other sources	1587:1609	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	9	82	from	sources	1603:1609	arg1	characterizations					1566:1582	Future characterizations	1559:1582	Future characterizations of CMPs from other sources	1559:1609	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	1	83	theme	embryonic	445:453	arg1	SEAP					477:480	SEAP	477:480	SEAP	477:480	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	1	83	theme	embryonic	445:453	arg1	phosphatase					464:474	an NF-κB-dependent, secreted embryonic alkaline phosphatase	416:474	phosphatase	464:474	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29281684	7	84	dep	C.	1177:1178	arg1	albicans					1180:1187	albicans	1180:1187	albicans	1180:1187	SEAP production in response to C. albicans A9 mnn4Δ mutant CMP, lacking phosphomannosylations on N-linked glycans, was significantly greater (p ≤ 0.005) than SEAP responses to CMP derived from parental A9 (both serotype B).
29281684	9	85	theme	dependent	1710:1718	arg1	responses					1734:1742	TLR4 dependent innate immune responses	1705:1742	TLR4 dependent innate immune responses targeting different C. albicans strains	1705:1782	Future characterizations of CMPs from other sources and their application in this model may provide further insight into variations observed with TLR4 dependent innate immune responses targeting different C. albicans strains.
29281684	1	86	theme	phosphatase	464:474	arg1	gene					492:495	an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	416:495	an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene	416:495	The ability of soluble C. albicans 20A (serotype A) mannoprotein (CMP) to serve as a ligand for toll-like receptor 4 (TLR4) and its co-receptors was examined using commercially available and stably-transfected HEK293 cells that express human TLR4, MD2 and CD14, but not MR. These TLR4 reporter cells also express an NF-κB-dependent, secreted embryonic alkaline phosphatase (SEAP) reporter gene.
29269413	7	0	theme	protein	1370:1376	arg1	levels					1378:1383	Notch1 protein levels	1363:1383	Notch1 protein levels	1363:1383	Moreover, β1,4GalTV promoted β1,4-galactosylation of Notch1 and increased Notch1 protein levels.
29269413	8	1	theme	ectopic	1395:1401	arg1	expression					1403:1412	ectopic expression	1395:1412	ectopic expression of activated Notch1	1395:1432	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	6	2	theme	glioma	1157:1162	arg1	transdifferentiation					1179:1198	glioma stem-like cell transdifferentiation	1157:1198	glioma stem-like cell transdifferentiation into endothelial cells	1157:1221	We also found that β1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required β1,4GalTV galactosylation activity.
29269413	2	3	theme	tumor	386:390	arg1	angiogenesis					392:403	tumor angiogenesis	386:403	tumor angiogenesis	386:403	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	8	4	theme	β1,4GalTV	1467:1475	arg1	depletion					1477:1485	β1,4GalTV depletion	1467:1485	β1,4GalTV depletion	1467:1485	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	9	5	theme	endothelial	1646:1656	arg1	cells					1658:1662	endothelial cells	1646:1662	endothelial cells	1646:1662	In summary, our findings indicate that β1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling.
29269413	5	6	theme	β1,4GalTV	967:975	arg1	knockdown					977:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	6	7	theme	β1,4GalTV	1253:1261	arg1	activity					1279:1286	β1,4GalTV galactosylation activity	1253:1286	β1,4GalTV galactosylation activity	1253:1286	We also found that β1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required β1,4GalTV galactosylation activity.
29269413	10	8	theme	glioma	1770:1775	arg1	angiogenesis					1777:1788	glioma angiogenesis	1770:1788	glioma angiogenesis	1770:1788	These detailed insights shed important light on the mechanisms regulating glioma angiogenesis.
29269413	6	9	theme	β1,4GalTV	1122:1130	arg1	overexpression					1132:1145	β1,4GalTV overexpression	1122:1145	β1,4GalTV overexpression	1122:1145	We also found that β1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required β1,4GalTV galactosylation activity.
29269413	8	10	from	effect	1457:1462	arg1	transdifferentiation					1512:1531	glioma stem-like cell transdifferentiation	1490:1531	glioma stem-like cell transdifferentiation	1490:1531	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	5	11	theme	RNA-mediated	954:965	arg1	knockdown					977:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	7	12	theme	Notch1	1363:1368	arg1	levels					1378:1383	Notch1 protein levels	1363:1383	Notch1 protein levels	1363:1383	Moreover, β1,4GalTV promoted β1,4-galactosylation of Notch1 and increased Notch1 protein levels.
29269413	4	13	theme	GlcNAcβ1-6Man	708:720	arg1	N-glycans					742:750	the branched N-glycans	729:750	the branched N-glycans	729:750	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	4	13	theme	GlcNAcβ1-6Man	708:720	arg1	arm					722:724	the GlcNAcβ1-6Man arm	704:724	the GlcNAcβ1-6Man arm of the branched N-glycans	704:750	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	8	14	theme	stem-like	1497:1505	arg1	transdifferentiation					1512:1531	glioma stem-like cell transdifferentiation	1490:1531	glioma stem-like cell transdifferentiation	1490:1531	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	3	15	theme	structures	576:585	arg1	expression					537:546	altered expression	529:546	altered expression of N-linked oligosaccharide structures on the cell surface	529:605	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
29269413	9	16	theme	glioma	1618:1623	arg1	cells					1635:1639	glioma stem-like cells	1618:1639	glioma stem-like cells	1618:1639	In summary, our findings indicate that β1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling.
29269413	7	17	theme	Notch1	1342:1347	arg1	β1,4-galactosylation					1318:1337	β1,4-galactosylation	1318:1337	β1,4-galactosylation of Notch1	1318:1347	Moreover, β1,4GalTV promoted β1,4-galactosylation of Notch1 and increased Notch1 protein levels.
29269413	6	18	theme	galactosylation	1263:1277	arg1	activity					1279:1286	β1,4GalTV galactosylation activity	1253:1286	β1,4GalTV galactosylation activity	1253:1286	We also found that β1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required β1,4GalTV galactosylation activity.
29269413	3	19	theme	altered	529:535	arg1	expression					537:546	altered expression	529:546	altered expression of N-linked oligosaccharide structures on the cell surface	529:605	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
29269413	2	20	theme	stem-like	296:304	arg1	cells					306:310	glioma stem-like cells	289:310	glioma stem-like cells	289:310	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	2	21	theme	therapeutic	435:445	arg1	options					447:453	new therapeutic options	431:453	new therapeutic options	431:453	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	0	22	theme	endothelial	127:137	arg1	cells					139:143	endothelial cells	127:143	endothelial cells	127:143	β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.
29269413	8	23	theme	depletion	1477:1485	arg1	effect					1457:1462	the inhibitory effect	1442:1462	the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation	1442:1531	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	3	24	from	expression	537:546	arg1	surface					599:605	the cell surface	590:605	the cell surface	590:605	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
29269413	2	25	theme	glioma	289:294	arg1	cells					306:310	glioma stem-like cells	289:310	glioma stem-like cells	289:310	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	1	26	theme	aggressive	199:208	arg1	cancers					216:222	the most aggressive human cancers	190:222	the most aggressive human cancers	190:222	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	0	27	from	signaling	46:54	arg1	cells					76:80	glioma stem-like cells	59:80	glioma stem-like cells	59:80	β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.
29269413	6	28	theme	endothelial	1205:1215	arg1	cells					1217:1221	endothelial cells	1205:1221	endothelial cells	1205:1221	We also found that β1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required β1,4GalTV galactosylation activity.
29269413	4	29	theme	branched	733:740	arg1	N-glycans					742:750	the branched N-glycans	729:750	the branched N-glycans	729:750	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	5	30	theme	glioma	1017:1022	arg1	cells					1034:1038	glioma stem-like cells	1017:1038	glioma stem-like cells	1017:1038	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	1	31	theme	human	210:214	arg1	cancers					216:222	the most aggressive human cancers	190:222	the most aggressive human cancers	190:222	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	0	32	theme	β1,4-Galactosyltransferase	0:25	arg1	V					27:27	β1,4-Galactosyltransferase V	0:27	β1,4-Galactosyltransferase V	0:27	β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.
29269413	5	33	theme	stem-like	1024:1032	arg1	cells					1034:1038	glioma stem-like cells	1017:1038	glioma stem-like cells	1017:1038	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	1	34	theme	cancers	216:222	arg1	one					183:185	one	183:185	one	183:185	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	1	34	theme	cancers	216:222	arg1	cancers					216:222	the most aggressive human cancers	190:222	the most aggressive human cancers	190:222	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	0	35	theme	Notch1	39:44	arg1	signaling					46:54	Notch1 signaling	39:54	Notch1 signaling in glioma stem-like cells	39:80	β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.
29269413	10	36	theme	detailed	1702:1709	arg1	insights					1711:1718	These detailed insights	1696:1718	These detailed insights	1696:1718	These detailed insights shed important light on the mechanisms regulating glioma angiogenesis.
29269413	8	37	theme	inhibitory	1446:1455	arg1	effect					1457:1462	the inhibitory effect	1442:1462	the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation	1442:1531	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	2	38	theme	endothelial	336:346	arg1	cells					348:352	endothelial cells	336:352	endothelial cells	336:352	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	6	39	theme	stem-like	1164:1172	arg1	transdifferentiation					1179:1198	glioma stem-like cell transdifferentiation	1157:1198	glioma stem-like cell transdifferentiation into endothelial cells	1157:1221	We also found that β1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required β1,4GalTV galactosylation activity.
29269413	4	40	theme	β1,4-galactosyltransferase	641:666	arg1	β1,4GalTV					671:679	β1,4GalTV	671:679	β1,4GalTV	671:679	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	4	40	theme	β1,4-galactosyltransferase	641:666	arg1	V					668:668	β1,4-galactosyltransferase V	641:668	β1,4-galactosyltransferase V (β1,4GalTV)	641:680	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	3	41	theme	oligosaccharide	560:574	arg1	structures					576:585	N-linked oligosaccharide structures	551:585	N-linked oligosaccharide structures	551:585	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
29269413	2	42	theme	glioblastoma	459:470	arg1	treatment					472:480	glioblastoma treatment	459:480	glioblastoma treatment	459:480	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	2	43	theme	new	368:370	arg1	mechanism					372:380	a new mechanism	366:380	a new mechanism for tumor angiogenesis	366:403	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	2	44	theme	Recent	255:260	arg1	studies					262:268	Recent studies	255:268	Recent studies	255:268	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	3	45	theme	Glioma	483:488	arg1	malignancy					490:499	Glioma malignancy	483:499	Glioma malignancy	483:499	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
29269413	4	46	theme	N-glycans	742:750	arg1	N-glycans					742:750	the branched N-glycans	729:750	the branched N-glycans	729:750	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	4	46	theme	N-glycans	742:750	arg1	arm					722:724	the GlcNAcβ1-6Man arm	704:724	the GlcNAcβ1-6Man arm of the branched N-glycans	704:750	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	1	47	theme	low	235:237	arg1	rates					248:252	very low survival rates	230:252	very low survival rates	230:252	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	0	48	theme	stem-like	66:74	arg1	cells					76:80	glioma stem-like cells	59:80	glioma stem-like cells	59:80	β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.
29269413	9	49	theme	cells	1635:1639	arg1	transdifferentiation					1594:1613	transdifferentiation	1594:1613	transdifferentiation of glioma stem-like cells into endothelial cells	1594:1662	In summary, our findings indicate that β1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling.
29269413	8	50	theme	cell	1507:1510	arg1	transdifferentiation					1512:1531	glioma stem-like cell transdifferentiation	1490:1531	glioma stem-like cell transdifferentiation	1490:1531	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	9	51	theme	stem-like	1625:1633	arg1	cells					1635:1639	glioma stem-like cells	1618:1639	glioma stem-like cells	1618:1639	In summary, our findings indicate that β1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling.
29269413	3	52	theme	N-linked	551:558	arg1	structures					576:585	N-linked oligosaccharide structures	551:585	N-linked oligosaccharide structures	551:585	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
29269413	0	53	theme	glioma	59:64	arg1	cells					76:80	glioma stem-like cells	59:80	glioma stem-like cells	59:80	β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.
29269413	10	54	theme	important	1725:1733	arg1	light					1735:1739	important light	1725:1739	important light	1725:1739	These detailed insights shed important light on the mechanisms regulating glioma angiogenesis.
29269413	4	55	theme	glioma	889:894	arg1	growth					896:901	glioma growth	889:901	glioma growth	889:901	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	1	56	theme	Malignant	146:154	arg1	multiforme					169:178	Malignant glioblastoma multiforme	146:178	Malignant glioblastoma multiforme	146:178	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	3	57	link	N-linked	551:558	arg1	structures					576:585	N-linked oligosaccharide structures	551:585	N-linked oligosaccharide structures	551:585	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
29269413	5	58	theme	short	940:944	arg1	knockdown					977:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	5	59	theme	endothelial	1084:1094	arg1	cells					1096:1100	endothelial cells	1084:1100	endothelial cells	1084:1100	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	1	60	theme	glioblastoma	156:167	arg1	multiforme					169:178	Malignant glioblastoma multiforme	146:178	Malignant glioblastoma multiforme	146:178	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	5	61	theme	cells	1034:1038	arg1	tumorigenesis					1000:1012	the tumorigenesis	996:1012	the tumorigenesis of glioma stem-like cells	996:1038	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	1	62	theme	survival	239:246	arg1	rates					248:252	very low survival rates	230:252	very low survival rates	230:252	Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates.
29269413	6	63	theme	cell	1174:1177	arg1	transdifferentiation					1179:1198	glioma stem-like cell transdifferentiation	1157:1198	glioma stem-like cell transdifferentiation into endothelial cells	1157:1221	We also found that β1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required β1,4GalTV galactosylation activity.
29269413	4	64	theme	glioma	796:801	arg1	growth					808:813	glioma cell growth	796:813	glioma cell growth	796:813	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	8	65	theme	glioma	1490:1495	arg1	transdifferentiation					1512:1531	glioma stem-like cell transdifferentiation	1490:1531	glioma stem-like cell transdifferentiation	1490:1531	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	4	66	theme	cell	803:806	arg1	growth					808:813	glioma cell growth	796:813	glioma cell growth	796:813	We have previously reported that β1,4-galactosyltransferase V (β1,4GalTV), which galactosylates the GlcNAcβ1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which β1,4GalTV stimulates glioma growth is unknown.
29269413	9	67	theme	Notch1	1678:1683	arg1	signaling					1685:1693	Notch1 signaling	1678:1693	Notch1 signaling	1678:1693	In summary, our findings indicate that β1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling.
29269413	8	68	theme	Notch1	1427:1432	arg1	expression					1403:1412	ectopic expression	1395:1412	ectopic expression of activated Notch1	1395:1432	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	8	69	theme	activated	1417:1425	arg1	Notch1					1427:1432	activated Notch1	1417:1432	activated Notch1	1417:1432	Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of β1,4GalTV depletion on glioma stem-like cell transdifferentiation.
29269413	5	70	theme	hairpin	946:952	arg1	knockdown					977:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	short hairpin RNA-mediated β1,4GalTV knockdown	940:985	Here we demonstrate that short hairpin RNA-mediated β1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells.
29269413	2	71	theme	new	431:433	arg1	options					447:453	new therapeutic options	431:453	new therapeutic options	431:453	Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment.
29269413	3	72	theme	cell	594:597	arg1	surface					599:605	the cell surface	590:605	the cell surface	590:605	Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface.
28926408	10	0	theme	elevated	1377:1384	arg1	levels					1386:1391	elevated levels	1377:1391	elevated levels of IgG antibodies to specific glycans	1377:1429	CONCLUSIONS HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans.
28926408	7	1	theme	Antiglycan	905:914	arg1	antibodies					920:929	RESULTS Antiglycan IgG antibodies	897:929	RESULTS Antiglycan IgG antibodies	897:929	RESULTS Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection.
28926408	7	2	theme	HIV	980:982	arg1	infection					984:992	HIV infection	980:992	HIV infection	980:992	RESULTS Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection.
28926408	11	3	with	individuals	1498:1508	arg1	bNAbs					1515:1519	bNAbs	1515:1519	bNAbs	1515:1519	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	0	4	theme	neutralizing	93:104	arg1	responses					106:114	broadly neutralizing responses	85:114	broadly neutralizing responses	85:114	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	7	5	theme	infection	984:992	arg1	irrespective					964:975	irrespective	964:975	irrespective	964:975	RESULTS Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection.
28926408	1	6	theme	HIV-1	132:136	arg1	envelope					138:145	The HIV-1 envelope	128:145	The HIV-1 envelope	128:145	BACKGROUND The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses.
28926408	11	7	theme	unique	1535:1540	arg1	informative					1564:1574	informative	1564:1574	informative	1564:1574	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	11	7	theme	unique	1535:1540	arg1	phenotype					1542:1550	a unique phenotype	1533:1550	a unique phenotype that may be informative for HIV vaccine design	1533:1597	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	6	8	theme	HIV-1	829:833	arg1	proteins					841:848	HIV-1 gp120 proteins	829:848	HIV-1 gp120 proteins	829:848	HIV-1 gp120 proteins were used to compete for binding to the array.
28926408	9	9	theme	antibodies	1236:1245	arg1	proportion					1197:1206	a proportion	1195:1206	a proportion of these glycan-binding IgG antibodies	1195:1245	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	9	9	theme	antibodies	1236:1245	arg1	HIV-1-specific					1252:1265	HIV-1-specific	1252:1265	HIV-1-specific	1252:1265	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	9	9	theme	antibodies	1236:1245	arg1	higher					1287:1292	higher	1287:1292	higher	1287:1292	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	9	10	dep	HIV-1-specific	1252:1265	arg1	proportion					1197:1206	a proportion	1195:1206	a proportion of these glycan-binding IgG antibodies	1195:1245	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	9	10	dep	HIV-1-specific	1252:1265	arg1	HIV-1-specific					1252:1265	HIV-1-specific	1252:1265	HIV-1-specific	1252:1265	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	9	10	dep	HIV-1-specific	1252:1265	arg1	higher					1287:1292	higher	1287:1292	higher	1287:1292	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	1	11	dep	BACKGROUND	117:126	arg1	covered					150:156	covered	150:156	is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses	147:262	BACKGROUND The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses.
28926408	1	12	theme	structural	184:193	arg1	integrity					195:203	structural integrity	184:203	structural integrity	184:203	BACKGROUND The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses.
28926408	0	13	theme	responses	106:114	arg1	development					70:80	the development	66:80	the development of broadly neutralizing responses	66:114	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	13	theme	responses	106:114	arg1	antibodies					25:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	13	theme	responses	106:114	arg1	infection					45:53	HIV-1 infection	39:53	HIV-1 infection	39:53	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	6	14	used	used	855:858	arg2	proteins					841:848	HIV-1 gp120 proteins	829:848	HIV-1 gp120 proteins	829:848	HIV-1 gp120 proteins were used to compete for binding to the array.
28926408	11	15	theme	antiglycan	1450:1459	arg1	antibodies					1465:1474	some antiglycan IgG antibodies	1445:1474	some antiglycan IgG antibodies	1445:1474	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	0	16	theme	glycan-binding	6:19	arg1	development					70:80	the development	66:80	the development of broadly neutralizing responses	66:114	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	16	theme	glycan-binding	6:19	arg1	antibodies					25:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	16	theme	glycan-binding	6:19	arg1	infection					45:53	HIV-1 infection	39:53	HIV-1 infection	39:53	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	9	17	theme	glycan-binding	1217:1230	arg1	antibodies					1236:1245	these glycan-binding IgG antibodies	1211:1245	these glycan-binding IgG antibodies	1211:1245	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	2	18	theme	neutralizing	320:331	arg1	bNAbs					345:349	bNAbs	345:349	bNAbs	345:349	However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals.
28926408	2	18	theme	neutralizing	320:331	arg1	antibodies					333:342	broadly neutralizing antibodies	312:342	broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals	312:395	However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals.
28926408	11	19	theme	IgG	1461:1463	arg1	antibodies					1465:1474	some antiglycan IgG antibodies	1445:1474	some antiglycan IgG antibodies	1445:1474	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	3	20	theme	antiglycan	428:437	arg1	antibodies					443:452	antiglycan IgG antibodies	428:452	antiglycan IgG antibodies	428:452	We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
28926408	3	20	theme	antiglycan	428:437	arg1	response					468:475	a general response	458:475	a general response to HIV-1 infection or specific to individuals who develop bNAbs	458:539	We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
28926408	0	21	theme	Serum	0:4	arg1	development					70:80	the development	66:80	the development of broadly neutralizing responses	66:114	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	21	theme	Serum	0:4	arg1	antibodies					25:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	21	theme	Serum	0:4	arg1	infection					45:53	HIV-1 infection	39:53	HIV-1 infection	39:53	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	9	22	theme	IgG	1232:1234	arg1	antibodies					1236:1245	these glycan-binding IgG antibodies	1211:1245	these glycan-binding IgG antibodies	1211:1245	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	2	23	theme	broadly	312:318	arg1	bNAbs					345:349	bNAbs	345:349	bNAbs	345:349	However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals.
28926408	2	23	theme	broadly	312:318	arg1	antibodies					333:342	broadly neutralizing antibodies	312:342	broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals	312:395	However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals.
28926408	10	24	theme	HIV-1	1342:1346	arg1	infection					1348:1356	CONCLUSIONS HIV-1 infection	1330:1356	CONCLUSIONS HIV-1 infection	1330:1356	CONCLUSIONS HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans.
28926408	3	25	theme	IgG	439:441	arg1	antibodies					443:452	antiglycan IgG antibodies	428:452	antiglycan IgG antibodies	428:452	We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
28926408	3	25	theme	IgG	439:441	arg1	response					468:475	a general response	458:475	a general response to HIV-1 infection or specific to individuals who develop bNAbs	458:539	We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
28926408	4	26	contain	contained	604:612	arg1	arrays					592:597	arrays	592:597	arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides	592:697	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	4	26	contain	contained	604:612	arg2	components					625:634	245 unique components	614:634	245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides	614:697	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	4	26	contain	contained	604:612	arg2	glycolipids					670:680	glycolipids	670:680	glycolipids	670:680	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	4	26	contain	contained	604:612	arg2	Tn-peptides					687:697	Tn-peptides	687:697	Tn-peptides	687:697	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	4	26	contain	contained	604:612	arg2	carbohydrates					655:667	N-linked carbohydrates	646:667	N-linked carbohydrates	646:667	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	5	27	theme	HIV-negative	713:724	arg1	women					746:750	20 HIV-negative and 27 HIV-positive women	710:750	20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs)	710:797	Sera from 20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs) were profiled longitudinally.
28926408	7	28	theme	3-year	949:954	arg1	period					956:961	a 3-year period	947:961	a 3-year period	947:961	RESULTS Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection.
28926408	10	29	theme	CONCLUSIONS	1330:1340	arg1	infection					1348:1356	CONCLUSIONS HIV-1 infection	1330:1356	CONCLUSIONS HIV-1 infection	1330:1356	CONCLUSIONS HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans.
28926408	4	30	theme	N-linked	646:653	arg1	carbohydrates					655:667	N-linked carbohydrates	646:667	N-linked carbohydrates	646:667	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	0	31	theme	IgG	21:23	arg1	development					70:80	the development	66:80	the development of broadly neutralizing responses	66:114	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	31	theme	IgG	21:23	arg1	antibodies					25:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	31	theme	IgG	21:23	arg1	infection					45:53	HIV-1 infection	39:53	HIV-1 infection	39:53	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	11	32	from	abundant	1486:1493	arg1	individuals					1498:1508	individuals	1498:1508	individuals with bNAbs	1498:1519	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	0	33	theme	HIV-1	39:43	arg1	antibodies					25:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	33	theme	HIV-1	39:43	arg1	infection					45:53	HIV-1 infection	39:53	HIV-1 infection	39:53	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	2	34	theme	HIV-infected	372:383	arg1	individuals					385:395	some HIV-infected individuals	367:395	some HIV-infected individuals	367:395	However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals.
28926408	1	35	theme	conserved	217:225	arg1	regions					227:233	conserved regions	217:233	conserved regions from host antibody responses	217:262	BACKGROUND The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses.
28926408	8	36	theme	HIV-positive	1004:1015	arg1	individuals					1017:1027	HIV-positive individuals	1004:1027	HIV-positive individuals	1004:1027	However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids.
28926408	5	37	theme	HIV-positive	733:744	arg1	women					746:750	20 HIV-negative and 27 HIV-positive women	710:750	20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs)	710:797	Sera from 20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs) were profiled longitudinally.
28926408	5	38	from	women	746:750	arg1	Sera					700:703	Sera	700:703	Sera from 20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs)	700:797	Sera from 20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs) were profiled longitudinally.
28926408	8	39	theme	elevated	1033:1040	arg1	binding					1042:1048	elevated binding	1033:1048	elevated binding to 40 components	1033:1065	However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids.
28926408	3	40	theme	general	460:466	arg1	antibodies					443:452	antiglycan IgG antibodies	428:452	antiglycan IgG antibodies	428:452	We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
28926408	3	40	theme	general	460:466	arg1	response					468:475	a general response	458:475	a general response to HIV-1 infection or specific to individuals who develop bNAbs	458:539	We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
28926408	10	41	theme	specific	1414:1421	arg1	glycans					1423:1429	specific glycans	1414:1429	specific glycans	1414:1429	CONCLUSIONS HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans.
28926408	8	42	theme	shock	1124:1128	arg1	protein					1130:1136	heat shock protein	1119:1136	heat shock protein	1119:1136	However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids.
28926408	7	43	theme	irrespective	964:975	arg1	period					956:961	a 3-year period	947:961	a 3-year period	947:961	RESULTS Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection.
28926408	4	44	theme	IgG	550:552	arg1	binding					554:560	METHODS IgG binding	542:560	METHODS IgG binding to glycans	542:571	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	1	45	from	responses	254:262	arg1	regions					227:233	conserved regions	217:233	conserved regions from host antibody responses	217:262	BACKGROUND The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses.
28926408	11	46	from	individuals	1498:1508	arg1	abundant					1486:1493	abundant	1486:1493	abundant	1486:1493	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	10	47	theme	antibodies	1400:1409	arg1	levels					1386:1391	elevated levels	1377:1391	elevated levels of IgG antibodies to specific glycans	1377:1429	CONCLUSIONS HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans.
28926408	4	48	theme	METHODS	542:548	arg1	binding					554:560	METHODS IgG binding	542:560	METHODS IgG binding to glycans	542:571	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	5	49	dep	women	746:750	arg1	including					753:761	including	753:761	including 12 individuals who developed bNAbs	753:796	Sera from 20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs) were profiled longitudinally.
28926408	0	50	dep	antibodies	25:34	arg1	development					70:80	the development	66:80	the development of broadly neutralizing responses	66:114	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	50	dep	antibodies	25:34	arg1	antibodies					25:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies	0:34	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	0	50	dep	antibodies	25:34	arg1	infection					45:53	HIV-1 infection	39:53	HIV-1 infection	39:53	Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
28926408	6	51	theme	gp120	835:839	arg1	proteins					841:848	HIV-1 gp120 proteins	829:848	HIV-1 gp120 proteins	829:848	HIV-1 gp120 proteins were used to compete for binding to the array.
28926408	3	52	theme	HIV-1	480:484	arg1	infection					486:494	HIV-1 infection	480:494	HIV-1 infection	480:494	We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
28926408	11	53	theme	vaccine	1584:1590	arg1	design					1592:1597	HIV vaccine design	1580:1597	HIV vaccine design	1580:1597	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	8	54	theme	heat	1119:1122	arg1	protein					1130:1136	heat shock protein	1119:1136	heat shock protein	1119:1136	However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids.
28926408	10	55	theme	IgG	1396:1398	arg1	antibodies					1400:1409	IgG antibodies	1396:1409	IgG antibodies to specific glycans	1396:1429	CONCLUSIONS HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans.
28926408	2	56	theme	antibodies	333:342	arg1	glycans					280:286	these glycans	274:286	these glycans	274:286	However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals.
28926408	2	56	theme	antibodies	333:342	arg1	target					302:307	the target	298:307	the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals	298:395	However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals.
28926408	7	57	theme	IgG	916:918	arg1	antibodies					920:929	RESULTS Antiglycan IgG antibodies	897:929	RESULTS Antiglycan IgG antibodies	897:929	RESULTS Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection.
28926408	1	58	theme	host	240:243	arg1	responses					254:262	host antibody responses	240:262	host antibody responses	240:262	BACKGROUND The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses.
28926408	11	59	theme	HIV	1580:1582	arg1	design					1592:1597	HIV vaccine design	1580:1597	HIV vaccine design	1580:1597	Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
28926408	4	60	link	N-linked	646:653	arg1	carbohydrates					655:667	N-linked carbohydrates	646:667	N-linked carbohydrates	646:667	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	9	61	theme	Competition	1156:1166	arg1	experiments					1168:1178	Competition experiments	1156:1178	Competition experiments	1156:1178	Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
28926408	1	62	theme	antibody	245:252	arg1	responses					254:262	host antibody responses	240:262	host antibody responses	240:262	BACKGROUND The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses.
28926408	8	63	contain	had	1029:1031	arg2	binding					1042:1048	elevated binding	1033:1048	elevated binding to 40 components	1033:1065	However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids.
28926408	8	63	contain	had	1029:1031	arg1	individuals					1017:1027	HIV-positive individuals	1004:1027	HIV-positive individuals	1004:1027	However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids.
28926408	7	64	theme	RESULTS	897:903	arg1	antibodies					920:929	RESULTS Antiglycan IgG antibodies	897:929	RESULTS Antiglycan IgG antibodies	897:929	RESULTS Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection.
28926408	4	65	theme	unique	618:623	arg1	carbohydrates					655:667	N-linked carbohydrates	646:667	N-linked carbohydrates	646:667	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	4	65	theme	unique	618:623	arg1	Tn-peptides					687:697	Tn-peptides	687:697	Tn-peptides	687:697	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	4	65	theme	unique	618:623	arg1	glycolipids					670:680	glycolipids	670:680	glycolipids	670:680	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28926408	4	65	theme	unique	618:623	arg1	components					625:634	245 unique components	614:634	245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides	614:697	METHODS IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides.
28750948	3	0	dep	muscle	412:417	arg1	amount					443:448	mitochondrial amount	429:448	mitochondrial amount	429:448	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	5	1	theme	mitochondrial	1059:1071	arg1	physiology					1073:1082	mitochondrial physiology	1059:1082	mitochondrial physiology	1059:1082	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	6	2	theme	cellular	1191:1198	arg1	capacity					1216:1223	cellular deglycosylation capacity	1191:1223	cellular deglycosylation capacity	1191:1223	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	6	2	theme	cellular	1191:1198	arg1	factor					1254:1259	a significant factor	1240:1259	a significant factor	1240:1259	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	3	3	from	function	454:461	arg1	children					470:477	two children	466:477	two children with a CDG subtype caused by NGLY1 deficiency	466:523	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	3	4	theme	mitochondrial	539:551	arg1	physiology					553:562	mitochondrial physiology	539:562	mitochondrial physiology	539:562	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	4	5	theme	pronounced	862:871	arg1	impairment					873:882	more pronounced impairment	857:882	more pronounced impairment of mitochondrial membrane potential	857:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	6	theme	cellular	980:987	arg1	capacity					1001:1008	reduced cellular respiratory capacity	972:1008	reduced cellular respiratory capacity	972:1008	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	3	7	theme	mitochondrial	429:441	arg1	amount					443:448	mitochondrial amount	429:448	mitochondrial amount	429:448	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	3	8	theme	human	581:585	arg1	fibroblasts					587:597	NGLY1 disease human fibroblasts	567:597	NGLY1 disease human fibroblasts	567:597	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	4	9	theme	increased	921:929	arg1	burden					960:965	increased mitochondrial matrix oxidant burden	921:965	increased mitochondrial matrix oxidant burden	921:965	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	3	10	theme	altered	404:410	arg1	muscle					412:417	altered muscle	404:417	altered muscle	404:417	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	4	11	theme	reduced	972:978	arg1	capacity					1001:1008	reduced cellular respiratory capacity	972:1008	reduced cellular respiratory capacity	972:1008	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	12	theme	mitochondrial	830:842	arg1	content					844:850	modestly reduced mitochondrial content	813:850	modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential	813:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	13	theme	consistent	741:750	arg1	present					795:801	present	795:801	present	795:801	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	13	theme	consistent	741:750	arg1	disruption					752:761	a consistent disruption	739:761	a consistent disruption of mitochondrial physiology	739:789	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	14	theme	mitochondrial	766:778	arg1	physiology					780:789	mitochondrial physiology	766:789	mitochondrial physiology	766:789	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	15	theme	matrix	945:950	arg1	burden					960:965	increased mitochondrial matrix oxidant burden	921:965	increased mitochondrial matrix oxidant burden	921:965	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	3	16	theme	NGLY1	567:571	arg1	fibroblasts					587:597	NGLY1 disease human fibroblasts	567:597	NGLY1 disease human fibroblasts	567:597	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	5	17	theme	NGLY1	1038:1042	arg1	expression					1044:1053	NGLY1 expression	1038:1053	NGLY1 expression	1038:1053	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	4	18	theme	cytosolic	711:719	arg1	deficiency					727:736	cytosolic NGLY1 deficiency	711:736	cytosolic NGLY1 deficiency	711:736	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	5	19	theme	Lentiviral	1011:1020	arg1	rescue					1022:1027	Lentiviral rescue	1011:1027	Lentiviral rescue	1011:1027	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	4	20	theme	mitochondrial	887:899	arg1	potential					910:918	mitochondrial membrane potential	887:918	mitochondrial membrane potential	887:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	2	21	theme	physiologic	267:277	arg1	connection					279:288	an essential physiologic connection	254:288	an essential physiologic connection	254:288	Here, we demonstrate that an essential physiologic connection exists between cellular N-linked deglycosylation capacity and mitochondrial function.
28750948	3	22	theme	liver	423:427	arg1	identification					386:399	identification	386:399	identification of altered muscle and liver mitochondrial amount	386:448	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	3	22	theme	liver	423:427	arg1	function					454:461	function	454:461	function in two children with a CDG subtype caused by NGLY1 deficiency	454:523	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	6	23	theme	divergent	1309:1317	arg1	species					1332:1338	divergent evolutionary species	1309:1338	divergent evolutionary species	1309:1338	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	5	24	from	expression	1044:1053	arg1	fibroblasts					1103:1113	human and mouse fibroblasts	1087:1113	human and mouse fibroblasts	1087:1113	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	1	25	dep	clinical	149:156	arg1	overlap					158:164	overlap	158:164	overlap	158:164	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	4	26	theme	respiratory	989:999	arg1	capacity					1001:1008	reduced cellular respiratory capacity	972:1008	reduced cellular respiratory capacity	972:1008	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	27	theme	deficiency	727:736	arg1	models					701:706	these distinct evolutionary models	673:706	these distinct evolutionary models of cytosolic NGLY1 deficiency	673:736	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	0	28	theme	Mitochondrial	0:12	arg1	function					14:21	Mitochondrial function	0:21	Mitochondrial function	0:21	Mitochondrial function requires NGLY1.
28750948	4	29	theme	oxidant	952:958	arg1	burden					960:965	increased mitochondrial matrix oxidant burden	921:965	increased mitochondrial matrix oxidant burden	921:965	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	1	30	theme	congenital	89:98	arg1	disorders					100:108	congenital disorders	89:108	congenital disorders of glycosylation (CDG)	89:131	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	3	31	from	identification	386:399	arg1	children					470:477	two children	466:477	two children with a CDG subtype caused by NGLY1 deficiency	466:523	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	3	32	theme	muscle	412:417	arg1	identification					386:399	identification	386:399	identification of altered muscle and liver mitochondrial amount	386:448	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	3	32	theme	muscle	412:417	arg1	function					454:461	function	454:461	function in two children with a CDG subtype caused by NGLY1 deficiency	454:523	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	3	33	theme	C.	654:655	arg1	elegans					657:663	C. elegans	654:663	C. elegans	654:663	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	2	34	theme	N-linked	314:321	arg1	capacity					339:346	cellular N-linked deglycosylation capacity	305:346	cellular N-linked deglycosylation capacity	305:346	Here, we demonstrate that an essential physiologic connection exists between cellular N-linked deglycosylation capacity and mitochondrial function.
28750948	4	35	theme	distinct	679:686	arg1	models					701:706	these distinct evolutionary models	673:706	these distinct evolutionary models of cytosolic NGLY1 deficiency	673:736	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	2	36	theme	deglycosylation	323:337	arg1	capacity					339:346	cellular N-linked deglycosylation capacity	305:346	cellular N-linked deglycosylation capacity	305:346	Here, we demonstrate that an essential physiologic connection exists between cellular N-linked deglycosylation capacity and mitochondrial function.
28750948	4	37	with	content	844:850	arg1	impairment					873:882	more pronounced impairment	857:882	more pronounced impairment of mitochondrial membrane potential	857:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	5	38	theme	mouse	1097:1101	arg1	fibroblasts					1103:1113	human and mouse fibroblasts	1087:1113	human and mouse fibroblasts	1087:1113	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	2	39	theme	cellular	305:312	arg1	capacity					339:346	cellular N-linked deglycosylation capacity	305:346	cellular N-linked deglycosylation capacity	305:346	Here, we demonstrate that an essential physiologic connection exists between cellular N-linked deglycosylation capacity and mitochondrial function.
28750948	4	40	with	capacity	1001:1008	arg1	impairment					873:882	more pronounced impairment	857:882	more pronounced impairment of mitochondrial membrane potential	857:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	1	41	theme	distinct	193:200	arg1	pathophysiology					211:225	distinct cellular pathophysiology	193:225	distinct cellular pathophysiology	193:225	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	5	42	theme	human	1087:1091	arg1	fibroblasts					1103:1113	human and mouse fibroblasts	1087:1113	human and mouse fibroblasts	1087:1113	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	3	43	theme	CDG	486:488	arg1	subtype					490:496	a CDG subtype	484:496	a CDG subtype caused by NGLY1 deficiency	484:523	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	4	44	theme	potential	910:918	arg1	impairment					873:882	more pronounced impairment	857:882	more pronounced impairment of mitochondrial membrane potential	857:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	45	theme	NGLY1	721:725	arg1	deficiency					727:736	cytosolic NGLY1 deficiency	711:736	cytosolic NGLY1 deficiency	711:736	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	1	46	theme	cellular	202:209	arg1	pathophysiology					211:225	distinct cellular pathophysiology	193:225	distinct cellular pathophysiology	193:225	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	2	47	link	N-linked	314:321	arg1	capacity					339:346	cellular N-linked deglycosylation capacity	305:346	cellular N-linked deglycosylation capacity	305:346	Here, we demonstrate that an essential physiologic connection exists between cellular N-linked deglycosylation capacity and mitochondrial function.
28750948	4	48	theme	membrane	901:908	arg1	potential					910:918	mitochondrial membrane potential	887:918	mitochondrial membrane potential	887:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	49	theme	evolutionary	688:699	arg1	models					701:706	these distinct evolutionary models	673:706	these distinct evolutionary models of cytosolic NGLY1 deficiency	673:736	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	3	50	theme	mouse	622:626	arg1	fibroblasts					638:648	NGLY1-knockout mouse embryonic fibroblasts	607:648	NGLY1-knockout mouse embryonic fibroblasts	607:648	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	6	51	from	factor	1254:1259	arg1	pathogenesis					1289:1300	mitochondrial RC disease pathogenesis	1264:1300	mitochondrial RC disease pathogenesis across divergent evolutionary species	1264:1338	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	1	52	theme	glycosylation	113:125	arg1	diseases					76:83	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	1	52	theme	glycosylation	113:125	arg1	disorders					100:108	congenital disorders	89:108	congenital disorders of glycosylation (CDG)	89:131	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	6	53	theme	deglycosylation	1200:1214	arg1	capacity					1216:1223	cellular deglycosylation capacity	1191:1223	cellular deglycosylation capacity	1191:1223	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	6	53	theme	deglycosylation	1200:1214	arg1	factor					1254:1259	a significant factor	1240:1259	a significant factor	1240:1259	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	4	54	theme	mitochondrial	931:943	arg1	burden					960:965	increased mitochondrial matrix oxidant burden	921:965	increased mitochondrial matrix oxidant burden	921:965	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	3	55	with	children	470:477	arg1	subtype					490:496	a CDG subtype	484:496	a CDG subtype caused by NGLY1 deficiency	484:523	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	3	56	theme	embryonic	628:636	arg1	fibroblasts					638:648	NGLY1-knockout mouse embryonic fibroblasts	607:648	NGLY1-knockout mouse embryonic fibroblasts	607:648	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	6	57	theme	mitochondrial	1264:1276	arg1	pathogenesis					1289:1300	mitochondrial RC disease pathogenesis	1264:1300	mitochondrial RC disease pathogenesis across divergent evolutionary species	1264:1338	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	5	58	from	physiology	1073:1082	arg1	fibroblasts					1103:1113	human and mouse fibroblasts	1087:1113	human and mouse fibroblasts	1087:1113	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	2	59	theme	essential	257:265	arg1	connection					279:288	an essential physiologic connection	254:288	an essential physiologic connection	254:288	Here, we demonstrate that an essential physiologic connection exists between cellular N-linked deglycosylation capacity and mitochondrial function.
28750948	2	60	theme	mitochondrial	352:364	arg1	function					366:373	mitochondrial function	352:373	mitochondrial function	352:373	Here, we demonstrate that an essential physiologic connection exists between cellular N-linked deglycosylation capacity and mitochondrial function.
28750948	4	61	theme	reduced	822:828	arg1	content					844:850	modestly reduced mitochondrial content	813:850	modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential	813:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	3	62	theme	disease	573:579	arg1	fibroblasts					587:597	NGLY1 disease human fibroblasts	567:597	NGLY1 disease human fibroblasts	567:597	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	5	63	theme	mitochondrial	1158:1170	arg1	function					1172:1179	mitochondrial function	1158:1179	mitochondrial function	1158:1179	Lentiviral rescue restored NGLY1 expression and mitochondrial physiology in human and mouse fibroblasts, confirming that NGLY1 directly influences mitochondrial function.
28750948	1	64	theme	Mitochondrial	39:51	arg1	RC					72:73	RC	72:73	RC	72:73	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	1	64	theme	Mitochondrial	39:51	arg1	chain					65:69	Mitochondrial respiratory chain	39:69	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	4	65	theme	physiology	780:789	arg1	present					795:801	present	795:801	present	795:801	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	4	65	theme	physiology	780:789	arg1	disruption					752:761	a consistent disruption	739:761	a consistent disruption of mitochondrial physiology	739:789	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28750948	6	66	theme	RC	1278:1279	arg1	pathogenesis					1289:1300	mitochondrial RC disease pathogenesis	1264:1300	mitochondrial RC disease pathogenesis across divergent evolutionary species	1264:1338	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	3	67	theme	NGLY1	508:512	arg1	deficiency					514:523	NGLY1 deficiency	508:523	NGLY1 deficiency	508:523	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	1	68	contain	have	188:191	arg2	pathophysiology					211:225	distinct cellular pathophysiology	193:225	distinct cellular pathophysiology	193:225	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	1	68	contain	have	188:191	arg1	diseases					76:83	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	1	69	theme	respiratory	53:63	arg1	RC					72:73	RC	72:73	RC	72:73	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	1	69	theme	respiratory	53:63	arg1	chain					65:69	Mitochondrial respiratory chain	39:69	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	6	70	theme	evolutionary	1319:1330	arg1	species					1332:1338	divergent evolutionary species	1309:1338	divergent evolutionary species	1309:1338	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	6	71	theme	significant	1242:1252	arg1	capacity					1216:1223	cellular deglycosylation capacity	1191:1223	cellular deglycosylation capacity	1191:1223	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	6	71	theme	significant	1242:1252	arg1	factor					1254:1259	a significant factor	1240:1259	a significant factor	1240:1259	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	6	72	theme	disease	1281:1287	arg1	pathogenesis					1289:1300	mitochondrial RC disease pathogenesis	1264:1300	mitochondrial RC disease pathogenesis across divergent evolutionary species	1264:1338	Overall, cellular deglycosylation capacity is shown to be a significant factor in mitochondrial RC disease pathogenesis across divergent evolutionary species.
28750948	1	73	theme	chain	65:69	arg1	diseases					76:83	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases	39:83	Mitochondrial respiratory chain (RC) diseases and congenital disorders of glycosylation (CDG) share extensive clinical overlap but are considered to have distinct cellular pathophysiology.
28750948	3	74	theme	NGLY1-knockout	607:620	arg1	fibroblasts					638:648	NGLY1-knockout mouse embryonic fibroblasts	607:648	NGLY1-knockout mouse embryonic fibroblasts	607:648	Following identification of altered muscle and liver mitochondrial amount and function in two children with a CDG subtype caused by NGLY1 deficiency, we evaluated mitochondrial physiology in NGLY1 disease human fibroblasts, and in NGLY1-knockout mouse embryonic fibroblasts and C. elegans.
28750948	4	75	with	burden	960:965	arg1	impairment					873:882	more pronounced impairment	857:882	more pronounced impairment of mitochondrial membrane potential	857:918	Across these distinct evolutionary models of cytosolic NGLY1 deficiency, a consistent disruption of mitochondrial physiology was present involving modestly reduced mitochondrial content with more pronounced impairment of mitochondrial membrane potential, increased mitochondrial matrix oxidant burden, and reduced cellular respiratory capacity.
28747680	0	0	theme	broad	64:68	arg1	antagonist					105:114	Eph receptor therapeutic antagonist	80:114	Eph receptor therapeutic antagonist	80:114	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	0	0	theme	broad	64:68	arg1	spectrum					70:77	a unique, long-acting and broad spectrum	38:77	a unique, long-acting and broad spectrum	38:77	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	2	1	theme	EphA4	454:458	arg1	Fc					460:461	EphA4 Fc	454:461	EphA4 Fc	454:461	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	1	theme	EphA4	454:458	arg1	Fc					450:451	IgG Fc	446:451	IgG Fc (EphA4 Fc)	446:462	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	2	theme	broad	545:549	arg1	Fc					536:537	EphA4 Fc	530:537	EphA4 Fc	530:537	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	2	theme	broad	545:549	arg1	spectrum					551:558	a broad spectrum	543:558	a broad spectrum Eph/ephrin antagonist	543:580	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	6	3	theme	cell	1040:1043	arg1	EphA4					1055:1059	cell expressed EphA4	1040:1059	cell expressed EphA4	1040:1059	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	5	4	dep	showed	900:905	arg1	such					864:867	such	864:867	such	864:867	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	1	5	theme	individual	325:334	arg1	proteins					340:347	targeting individual Eph proteins	315:347	targeting individual Eph proteins	315:347	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	1	6	theme	Eph	336:338	arg1	proteins					340:347	targeting individual Eph proteins	315:347	targeting individual Eph proteins	315:347	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	3	7	dep	in	605:606	arg1	vivo					608:611	vivo	608:611	vivo	608:611	However, a very short in vivo half-life effectively limited its therapeutic development.
28747680	2	8	theme	effective	472:480	arg1	protein					397:403	a soluble fusion protein	380:403	a soluble fusion protein	380:403	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	8	theme	effective	472:480	arg1	therapy					482:488	an effective therapy	469:488	an effective therapy	469:488	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	1	9	theme	proteins	340:347	arg1	effectiveness					298:310	the effectiveness	294:310	the effectiveness of targeting individual Eph proteins	294:347	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	5	10	theme	pharmacokinetic	929:943	arg1	characteristics					945:959	dramatically improved pharmacokinetic characteristics	907:959	dramatically improved pharmacokinetic characteristics	907:959	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	1	11	theme	non-neoplastic	239:252	arg1	diseases					254:261	non-neoplastic diseases	239:261	non-neoplastic diseases	239:261	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	5	12	link	N-linked	798:805	arg1	sites					807:811	three demonstrated N-linked sites	779:811	three demonstrated N-linked sites	779:811	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	6	13	from	use	1156:1158	arg1	diseases					1186:1193	both acute and chronic diseases	1163:1193	both acute and chronic diseases	1163:1193	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	6	14	theme	protein	975:981	arg1	stability					983:991	protein stability	975:991	protein stability	975:991	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	0	15	theme	receptor	84:91	arg1	antagonist					105:114	Eph receptor therapeutic antagonist	80:114	Eph receptor therapeutic antagonist	80:114	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	0	15	theme	receptor	84:91	arg1	spectrum					70:77	a unique, long-acting and broad spectrum	38:77	a unique, long-acting and broad spectrum	38:77	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	2	16	theme	acute	493:497	arg1	injuries					499:506	acute injuries	493:506	acute injuries	493:506	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	5	17	theme	N-linked	798:805	arg1	sites					807:811	three demonstrated N-linked sites	779:811	three demonstrated N-linked sites	779:811	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	2	18	theme	soluble	382:388	arg1	protein					397:403	a soluble fusion protein	380:403	a soluble fusion protein	380:403	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	18	theme	soluble	382:388	arg1	therapy					482:488	an effective therapy	469:488	an effective therapy	469:488	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	0	19	theme	Eph	80:82	arg1	antagonist					105:114	Eph receptor therapeutic antagonist	80:114	Eph receptor therapeutic antagonist	80:114	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	0	19	theme	Eph	80:82	arg1	spectrum					70:77	a unique, long-acting and broad spectrum	38:77	a unique, long-acting and broad spectrum	38:77	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	5	20	theme	Progressive	755:765	arg1	deletion					767:774	Progressive deletion	755:774	Progressive deletion of three demonstrated N-linked sites in EphA4	755:820	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	5	21	from	deletion	767:774	arg1	EphA4					816:820	EphA4	816:820	EphA4	816:820	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	2	22	theme	Eph/ephrin	560:569	arg1	antagonist					571:580	Eph/ephrin antagonist	560:580	a broad spectrum Eph/ephrin antagonist	543:580	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	4	23	theme	unique	684:689	arg1	approach					708:715	a unique glycoengineering approach	682:715	a unique glycoengineering approach to enhance the half-life of EphA4 Fc	682:752	We report a unique glycoengineering approach to enhance the half-life of EphA4 Fc.
28747680	2	24	dep	spectrum	551:558	arg1	antagonist					571:580	Eph/ephrin antagonist	560:580	a broad spectrum Eph/ephrin antagonist	543:580	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	3	25	theme	in	605:606	arg1	half-life					613:621	a very short in vivo half-life	592:621	a very short in vivo half-life	592:621	However, a very short in vivo half-life effectively limited its therapeutic development.
28747680	6	26	theme	Eph/ephrin	1130:1139	arg1	it					1091:1092	it	1091:1092	it	1091:1092	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	6	26	theme	Eph/ephrin	1130:1139	arg1	antagonist					1141:1150	a broad spectrum Eph/ephrin antagonist	1113:1150	a broad spectrum Eph/ephrin antagonist	1113:1150	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	5	27	theme	in	846:847	arg1	half-life					854:862	in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics	846:959	in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics	846:959	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	2	28	theme	EphA4	416:420	arg1	ectodomain					422:431	the EphA4 ectodomain	412:431	the EphA4 ectodomain	412:431	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	6	29	theme	broad	1115:1119	arg1	spectrum					1121:1128	a broad spectrum	1113:1128	a broad spectrum Eph/ephrin antagonist	1113:1150	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	5	30	theme	improved	920:927	arg1	characteristics					945:959	dramatically improved pharmacokinetic characteristics	907:959	dramatically improved pharmacokinetic characteristics	907:959	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	5	31	theme	demonstrated	785:796	arg1	sites					807:811	three demonstrated N-linked sites	779:811	three demonstrated N-linked sites	779:811	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	0	32	theme	EphA4	20:24	arg1	Fc					26:27	EphA4 Fc	20:27	EphA4 Fc	20:27	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	0	33	theme	therapeutic	93:103	arg1	antagonist					105:114	Eph receptor therapeutic antagonist	80:114	Eph receptor therapeutic antagonist	80:114	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	0	33	theme	therapeutic	93:103	arg1	spectrum					70:77	a unique, long-acting and broad spectrum	38:77	a unique, long-acting and broad spectrum	38:77	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	4	34	theme	glycoengineering	691:706	arg1	approach					708:715	a unique glycoengineering approach	682:715	a unique glycoengineering approach to enhance the half-life of EphA4 Fc	682:752	We report a unique glycoengineering approach to enhance the half-life of EphA4 Fc.
28747680	1	35	theme	neoplastic	175:184	arg1	disease					205:211	both neoplastic and non-neoplastic disease	170:211	both neoplastic and non-neoplastic disease	170:211	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	1	36	theme	function	278:285	arg1	redundancy					264:273	redundancy	264:273	redundancy of function	264:285	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	6	37	theme	EphA4	1055:1059	arg1	antagonism					1026:1035	antagonism	1026:1035	antagonism of cell expressed EphA4	1026:1059	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	6	37	theme	EphA4	1055:1059	arg1	affinity					994:1001	affinity	994:1001	affinity for ephrin ligands	994:1020	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	6	37	theme	EphA4	1055:1059	arg1	stability					983:991	protein stability	975:991	protein stability	975:991	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	5	38	theme	sites	807:811	arg1	deletion					767:774	Progressive deletion	755:774	Progressive deletion of three demonstrated N-linked sites in EphA4	755:820	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	2	39	theme	IgG	446:448	arg1	Fc					460:461	EphA4 Fc	454:461	EphA4 Fc	454:461	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	39	theme	IgG	446:448	arg1	Fc					450:451	IgG Fc	446:451	IgG Fc (EphA4 Fc)	446:462	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	0	40	theme	Fc	26:27	arg1	Glycoengineering					0:15	Glycoengineering	0:15	Glycoengineering of EphA4 Fc	0:27	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	1	41	theme	non-neoplastic	190:203	arg1	disease					205:211	both neoplastic and non-neoplastic disease	170:211	both neoplastic and non-neoplastic disease	170:211	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	0	42	theme	unique	40:45	arg1	antagonist					105:114	Eph receptor therapeutic antagonist	80:114	Eph receptor therapeutic antagonist	80:114	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	0	42	theme	unique	40:45	arg1	spectrum					70:77	a unique, long-acting and broad spectrum	38:77	a unique, long-acting and broad spectrum	38:77	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	2	43	theme	EphA4	530:534	arg1	Fc					536:537	EphA4 Fc	530:537	EphA4 Fc	530:537	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	43	theme	EphA4	530:534	arg1	spectrum					551:558	a broad spectrum	543:558	a broad spectrum Eph/ephrin antagonist	543:580	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	5	44	theme	triple	878:883	arg1	protein					892:898	the triple mutant protein	874:898	the triple mutant protein	874:898	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	6	45	theme	acute	1168:1172	arg1	diseases					1186:1193	both acute and chronic diseases	1163:1193	both acute and chronic diseases	1163:1193	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	4	46	theme	EphA4	745:749	arg1	Fc					751:752	EphA4 Fc	745:752	EphA4 Fc	745:752	We report a unique glycoengineering approach to enhance the half-life of EphA4 Fc.
28747680	5	47	dep	in	846:847	arg1	vivo					849:852	vivo	849:852	vivo	849:852	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	5	48	theme	mutant	885:890	arg1	protein					892:898	the triple mutant protein	874:898	the triple mutant protein	874:898	Progressive deletion of three demonstrated N-linked sites in EphA4 progressively increased in vivo half-life such that the triple mutant protein showed dramatically improved pharmacokinetic characteristics.
28747680	6	49	theme	spectrum	1121:1128	arg1	it					1091:1092	it	1091:1092	it	1091:1092	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	6	49	theme	spectrum	1121:1128	arg1	antagonist					1141:1150	a broad spectrum Eph/ephrin antagonist	1113:1150	a broad spectrum Eph/ephrin antagonist	1113:1150	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	3	50	theme	short	599:603	arg1	half-life					613:621	a very short in vivo half-life	592:621	a very short in vivo half-life	592:621	However, a very short in vivo half-life effectively limited its therapeutic development.
28747680	6	51	theme	chronic	1178:1184	arg1	diseases					1186:1193	both acute and chronic diseases	1163:1193	both acute and chronic diseases	1163:1193	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	1	52	from	therapy	159:165	arg1	disease					205:211	both neoplastic and non-neoplastic disease	170:211	both neoplastic and non-neoplastic disease	170:211	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	1	53	theme	Eph	117:119	arg1	receptors					121:129	Eph receptors	117:129	Eph receptors	117:129	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	2	54	from	therapy	482:488	arg1	injuries					499:506	acute injuries	493:506	acute injuries	493:506	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	0	55	theme	long-acting	48:58	arg1	antagonist					105:114	Eph receptor therapeutic antagonist	80:114	Eph receptor therapeutic antagonist	80:114	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	0	55	theme	long-acting	48:58	arg1	spectrum					70:77	a unique, long-acting and broad spectrum	38:77	a unique, long-acting and broad spectrum	38:77	Glycoengineering of EphA4 Fc leads to a unique, long-acting and broad spectrum, Eph receptor therapeutic antagonist.
28747680	2	56	theme	fusion	390:395	arg1	protein					397:403	a soluble fusion protein	380:403	a soluble fusion protein	380:403	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	2	56	theme	fusion	390:395	arg1	therapy					482:488	an effective therapy	469:488	an effective therapy	469:488	We have shown previously that a soluble fusion protein, where the EphA4 ectodomain was fused to IgG Fc (EphA4 Fc), was an effective therapy in acute injuries and demonstrated that EphA4 Fc was a broad spectrum Eph/ephrin antagonist.
28747680	6	57	theme	expressed	1045:1053	arg1	EphA4					1055:1059	cell expressed EphA4	1040:1059	cell expressed EphA4	1040:1059	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	6	58	theme	ephrin	1007:1012	arg1	ligands					1014:1020	ephrin ligands	1007:1020	ephrin ligands	1007:1020	Importantly, protein stability, affinity for ephrin ligands and antagonism of cell expressed EphA4 was fully preserved, enabling it to be developed as a broad spectrum Eph/ephrin antagonist for use in both acute and chronic diseases.
28747680	1	59	theme	targeting	315:323	arg1	proteins					340:347	targeting individual Eph proteins	315:347	targeting individual Eph proteins	315:347	Eph receptors have emerged as targets for therapy in both neoplastic and non-neoplastic disease, however, particularly in non-neoplastic diseases, redundancy of function limits the effectiveness of targeting individual Eph proteins.
28747680	4	60	theme	Fc	751:752	arg1	half-life					732:740	the half-life	728:740	the half-life of EphA4 Fc	728:752	We report a unique glycoengineering approach to enhance the half-life of EphA4 Fc.
28747680	3	61	theme	therapeutic	647:657	arg1	development					659:669	its therapeutic development	643:669	its therapeutic development	643:669	However, a very short in vivo half-life effectively limited its therapeutic development.
31636418	4	0	from	species	542:548	arg1	ligands					521:527	ligands	521:527	ligands from diverse species	521:548	Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species.
31636418	8	1	from	positions	1288:1296	arg1	surface					1314:1320	the receptor surface	1301:1320	the receptor surface	1301:1320	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	1	2	theme	African	155:161	arg1	trypanosomes					163:174	African trypanosomes	155:174	African trypanosomes	155:174	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	0	3	theme	recognition	79:89	arg1	mechanisms					58:67	mechanisms	58:67	mechanisms of ligand recognition and immune evasion	58:108	Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
31636418	8	4	located	found	1271:1275	arg1	contrast					1203:1210	contrast	1203:1210	contrast	1203:1210	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	8	4	located	found	1271:1275	arg2	glycans					1244:1250	N-linked glycans	1235:1250	N-linked glycans	1235:1250	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	8	4	located	found	1271:1275	arg2	sites					1225:1229	polymorphic sites	1213:1229	polymorphic sites	1213:1229	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	8	4	located	found	1271:1275	arg1	positions					1288:1296	exposed positions	1280:1296	exposed positions	1280:1296	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	0	5	theme	evasion	102:108	arg1	mechanisms					58:67	mechanisms	58:67	mechanisms of ligand recognition and immune evasion	58:108	Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
31636418	4	6	theme	diverse	534:540	arg1	species					542:548	diverse species	534:548	diverse species	534:548	Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species.
31636418	5	7	theme	transferrin	620:630	arg1	uptake					632:637	transferrin uptake	620:637	transferrin uptake	620:637	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	8	8	theme	receptor	1379:1386	arg1	diversification					1388:1402	transferrin receptor diversification	1367:1402	transferrin receptor diversification	1367:1402	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	0	9	theme	immune	95:100	arg1	evasion					102:108	immune evasion	95:108	immune evasion	95:108	Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
31636418	5	10	theme	brucei	685:690	arg1	receptor					704:711	a Trypanosoma brucei transferrin receptor	671:711	a Trypanosoma brucei transferrin receptor	671:711	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	5	11	theme	uptake	632:637	arg1	context					609:615	the context	605:615	the context of transferrin uptake	605:637	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	2	12	theme	macromolecular	289:302	arg1	nutrients					304:312	macromolecular nutrients	289:312	macromolecular nutrients such as transferrin2,3	289:335	Within these coats are receptors for macromolecular nutrients such as transferrin2,3.
31636418	2	12	theme	macromolecular	289:302	arg1	transferrin2,3					322:335	transferrin2,3	322:335	transferrin2,3	322:335	Within these coats are receptors for macromolecular nutrients such as transferrin2,3.
31636418	7	13	theme	receptor	1118:1125	arg1	variation					1127:1135	receptor variation	1118:1135	receptor variation	1118:1135	However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection.
31636418	8	14	theme	exposed	1280:1286	arg1	positions					1288:1296	exposed positions	1280:1296	exposed positions	1280:1296	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	5	15	theme	heterodimeric	765:777	arg1	receptor					779:786	this heterodimeric receptor	760:786	this heterodimeric receptor	760:786	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	5	16	theme	asymmetric	805:814	arg1	platform					831:838	a large asymmetric ligand-binding platform	797:838	a large asymmetric ligand-binding platform	797:838	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	5	17	with	complex	716:722	arg1	transferrin					735:745	human transferrin	729:745	human transferrin	729:745	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	5	18	theme	large	799:803	arg1	platform					831:838	a large asymmetric ligand-binding platform	797:838	a large asymmetric ligand-binding platform	797:838	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	7	19	theme	broad	1078:1082	arg1	range					1084:1088	a broad range	1076:1088	a broad range of mammals	1076:1099	However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection.
31636418	1	20	theme	remarkable	189:198	arg1	coats					208:212	remarkable surface coats	189:212	remarkable surface coats	189:212	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	6	21	contain	contains	864:871	arg1	genome					857:862	The trypanosome genome	841:862	The trypanosome genome	841:862	The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6.
31636418	6	21	contain	contains	864:871	arg2	family					875:880	a family	873:880	a family	873:880	The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6.
31636418	1	22	theme	surface	200:206	arg1	coats					208:212	remarkable surface coats	189:212	remarkable surface coats	189:212	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	0	23	theme	trypanosome	17:27	arg1	receptor					41:48	the trypanosome transferrin receptor	13:48	the trypanosome transferrin receptor	13:48	Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
31636418	8	24	link	N-linked	1235:1242	arg1	glycans					1244:1250	N-linked glycans	1235:1250	N-linked glycans	1235:1250	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	7	25	theme	mammals	1093:1099	arg1	range					1084:1088	a broad range	1076:1088	a broad range of mammals	1076:1099	However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection.
31636418	8	26	theme	N-linked	1235:1242	arg1	glycans					1244:1250	N-linked glycans	1235:1250	N-linked glycans	1235:1250	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	7	27	theme	infection	1189:1197	arg1	promiscuity					1169:1179	promiscuity	1169:1179	promiscuity of host infection	1169:1197	However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection.
31636418	5	28	theme	human	729:733	arg1	transferrin					735:745	human transferrin	729:745	human transferrin	729:745	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	6	29	theme	trypanosome	845:855	arg1	genome					857:862	The trypanosome genome	841:862	The trypanosome genome	841:862	The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6.
31636418	0	30	theme	receptor	41:48	arg1	Structure					0:8	Structure	0:8	Structure of the trypanosome transferrin receptor	0:48	Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
31636418	8	31	from	variation	1438:1446	arg1	receptor					1455:1462	the receptor to prolong survival in a host	1451:1492	the receptor to prolong survival in a host	1451:1492	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	4	32	theme	host	475:478	arg1	range					480:484	a wide host range	468:484	a wide host range	468:484	Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species.
31636418	8	33	theme	antigenic	1428:1436	arg1	variation					1438:1446	antigenic variation	1428:1446	antigenic variation in the receptor to prolong survival in a host	1428:1492	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	8	34	theme	receptor	1305:1312	arg1	surface					1314:1320	the receptor surface	1301:1320	the receptor surface	1301:1320	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	0	35	theme	transferrin	29:39	arg1	receptor					41:48	the trypanosome transferrin receptor	13:48	the trypanosome transferrin receptor	13:48	Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
31636418	6	36	theme	mammalian	990:998	arg1	hosts5,6					1000:1007	different mammalian hosts5,6	980:1007	different mammalian hosts5,6	980:1007	The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6.
31636418	5	37	theme	ligand-binding	816:829	arg1	platform					831:838	a large asymmetric ligand-binding platform	797:838	a large asymmetric ligand-binding platform	797:838	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	6	38	theme	transferrin	895:905	arg1	receptors4					907:916	around 14 transferrin receptors4	885:916	around 14 transferrin receptors4	885:916	The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6.
31636418	6	39	theme	receptors4	907:916	arg1	family					875:880	a family	873:880	a family	873:880	The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6.
31636418	6	40	theme	different	980:988	arg1	hosts5,6					1000:1007	different mammalian hosts5,6	980:1007	different mammalian hosts5,6	980:1007	The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6.
31636418	5	41	theme	transferrin	692:702	arg1	receptor					704:711	a Trypanosoma brucei transferrin receptor	671:711	a Trypanosoma brucei transferrin receptor	671:711	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	3	42	theme	immunoglobulin-mediated	418:440	arg1	attack					442:447	immunoglobulin-mediated attack	418:447	immunoglobulin-mediated attack	418:447	These must be accessible to their ligands but must not confer susceptibility to immunoglobulin-mediated attack.
31636418	5	43	theme	receptor	704:711	arg1	structure					658:666	the structure	654:666	the structure of a Trypanosoma brucei transferrin receptor	654:711	To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform.
31636418	7	44	theme	single	1034:1039	arg1	receptor					1041:1048	a single receptor	1032:1048	a single receptor	1032:1048	However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection.
31636418	1	45	theme	prolonged	123:131	arg1	infection					133:141	prolonged infection	123:141	prolonged infection of mammals	123:152	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	7	46	theme	host	1184:1187	arg1	infection					1189:1197	host infection	1184:1197	host infection	1184:1197	However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection.
31636418	4	47	theme	wide	470:473	arg1	range					480:484	a wide host range	468:484	a wide host range	468:484	Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species.
31636418	8	48	theme	transferrin	1367:1377	arg1	receptor					1379:1386	transferrin receptor	1367:1386	transferrin receptor diversification	1367:1402	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31636418	1	49	theme	antigenic	230:238	arg1	variation1					240:249	antigenic variation1	230:249	antigenic variation1	230:249	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	0	50	theme	ligand	72:77	arg1	recognition					79:89	ligand recognition	72:89	ligand recognition	72:89	Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.
31636418	1	51	theme	mammals	146:152	arg1	infection					133:141	prolonged infection	123:141	prolonged infection of mammals	123:152	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	1	52	theme	variation1	240:249	arg1	coats					208:212	remarkable surface coats	189:212	remarkable surface coats	189:212	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	1	52	theme	variation1	240:249	arg1	system					220:225	a system	218:225	a system of antigenic variation1	218:249	To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1.
31636418	8	53	theme	polymorphic	1213:1223	arg1	sites					1225:1229	polymorphic sites	1213:1229	polymorphic sites	1213:1229	In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host.
31336133	0	0	theme	human	78:82	arg1	IFN-α2b					84:90	human IFN-α2b	78:90	human IFN-α2b	78:90	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	2	1	gly	glycosylated	300:311	arg1	peptides					313:320	glycosylated peptides	300:320	glycosylated peptides	300:320	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	9	2	from	decrease	1371:1378	arg1	SBA					1440:1442	SBA	1440:1442	SBA	1440:1442	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	9	2	from	decrease	1371:1378	arg1	activities					1428:1437	their in vitro antiviral specific biological activities	1383:1437	their in vitro antiviral specific biological activities (SBA)	1383:1443	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	9	3	theme	in	1389:1390	arg1	SBA					1440:1442	SBA	1440:1442	SBA	1440:1442	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	9	3	theme	in	1389:1390	arg1	activities					1428:1437	their in vitro antiviral specific biological activities	1383:1437	their in vitro antiviral specific biological activities (SBA)	1383:1443	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	3	4	gly	N-glycosylation	558:572	arg2	2					546:546	2	546:546	2	546:546	The ANITVNITV peptide described by Perlmann and coworkers presents 9 amino acids and 2 potential N-glycosylation sites.
31336133	3	4	gly	N-glycosylation	558:572	arg2	sites					574:578	2 potential N-glycosylation sites	546:578	2 potential N-glycosylation sites	546:578	The ANITVNITV peptide described by Perlmann and coworkers presents 9 amino acids and 2 potential N-glycosylation sites.
31336133	13	5	theme	based	1903:1907	arg1	biobetter					1909:1917	an IFN-α based biobetter	1894:1917	an IFN-α based biobetter	1894:1917	This feature together with its improved pharmacokinetics encourages the development of IFN4NNter as an IFN-α based biobetter.
31336133	13	5	theme	based	1903:1907	arg1	development					1866:1876	the development	1862:1876	the development of IFN4NNter	1862:1889	This feature together with its improved pharmacokinetics encourages the development of IFN4NNter as an IFN-α based biobetter.
31336133	9	6	theme	specific	1408:1415	arg1	SBA					1440:1442	SBA	1440:1442	SBA	1440:1442	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	9	6	theme	specific	1408:1415	arg1	activities					1428:1437	their in vitro antiviral specific biological activities	1383:1437	their in vitro antiviral specific biological activities (SBA)	1383:1443	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	6	7	theme	N-linked	1038:1045	arg1	glycans					1047:1053	4 N-linked glycans	1036:1053	4 N-linked glycans	1036:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	10	8	with	comparison	1545:1554	arg1	molecules					1574:1582	the parental molecules	1561:1582	the parental molecules	1561:1582	However, in vitro antiproliferative SBA was differentially modified for IFNwtNter and IFN4NNter in comparison with the parental molecules.
31336133	6	9	theme	pharmacokinetic	869:883	arg1	properties					885:894	the physicochemical, biological and pharmacokinetic properties	833:894	the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans	833:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	12	10	theme	peptide	1702:1708	arg1	addition					1676:1683	the addition	1672:1683	the addition of the ANITVNITV peptide to the N-terminus of IFN4N	1672:1735	Remarkably, the addition of the ANITVNITV peptide to the N-terminus of IFN4N had a positive impact on its growth-inhibitory activity.
31336133	9	11	theme	biological	1417:1426	arg1	SBA					1440:1442	SBA	1440:1442	SBA	1440:1442	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	9	11	theme	biological	1417:1426	arg1	activities					1428:1437	their in vitro antiviral specific biological activities	1383:1437	their in vitro antiviral specific biological activities (SBA)	1383:1443	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	0	12	from	Effect	0:5	arg1	pharmacokinetics					58:73	pharmacokinetics	58:73	pharmacokinetics	58:73	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	0	12	from	Effect	0:5	arg1	bioactivity					42:52	bioactivity	42:52	bioactivity	42:52	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	12	13	theme	growth-inhibitory	1766:1782	arg1	activity					1784:1791	its growth-inhibitory activity	1762:1791	its growth-inhibitory activity	1762:1791	Remarkably, the addition of the ANITVNITV peptide to the N-terminus of IFN4N had a positive impact on its growth-inhibitory activity.
31336133	2	14	theme	glycosylated	300:311	arg1	peptides					313:320	glycosylated peptides	300:320	glycosylated peptides	300:320	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	0	15	theme	IFN-α2b	84:90	arg1	pharmacokinetics					58:73	pharmacokinetics	58:73	pharmacokinetics	58:73	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	0	15	theme	IFN-α2b	84:90	arg1	bioactivity					42:52	bioactivity	42:52	bioactivity	42:52	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	12	16	theme	ANITVNITV	1692:1700	arg1	peptide					1702:1708	the ANITVNITV peptide	1688:1708	the ANITVNITV peptide	1688:1708	Remarkably, the addition of the ANITVNITV peptide to the N-terminus of IFN4N had a positive impact on its growth-inhibitory activity.
31336133	6	17	contain	bears	1016:1020	arg1	site					964:967	a single O-glycosylation site	939:967	a single O-glycosylation site	939:967	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	17	contain	bears	1016:1020	arg3	addition					1026:1033	addition	1026:1033	addition	1026:1033	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	17	contain	bears	1016:1020	arg1	IFN4N					1003:1007	IFN4N	1003:1007	IFN4N	1003:1007	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	17	contain	bears	1016:1020	arg2	glycans					1047:1053	4 N-linked glycans	1036:1053	4 N-linked glycans	1036:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	17	contain	bears	1016:1020	arg1	variant					994:1000	a hyperglycosylated variant	974:1000	a hyperglycosylated variant (IFN4N)	974:1008	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	18	theme	fusion	823:828	arg1	influence					792:800	the influence	788:800	the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans	788:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	3	19	theme	amino	530:534	arg1	acids					536:540	9 amino acids	528:540	9 amino acids	528:540	The ANITVNITV peptide described by Perlmann and coworkers presents 9 amino acids and 2 potential N-glycosylation sites.
31336133	8	20	theme	new	1252:1254	arg1	molecules					1256:1264	the new molecules	1248:1264	the new molecules	1248:1264	Therefore, the pharmacokinetic properties of the new molecules were significantly improved.
31336133	0	21	theme	hyper-N-glycosylated	98:117	arg1	variant					119:125	a hyper-N-glycosylated variant	96:125	a hyper-N-glycosylated variant	96:125	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	10	22	theme	antiproliferative	1464:1480	arg1	SBA					1482:1484	in vitro antiproliferative SBA	1455:1484	in vitro antiproliferative SBA	1455:1484	However, in vitro antiproliferative SBA was differentially modified for IFNwtNter and IFN4NNter in comparison with the parental molecules.
31336133	6	23	gly	O-glycosylation	948:962	arg2	site					964:967	a single O-glycosylation site	939:967	a single O-glycosylation site	939:967	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	3	24	theme	potential	548:556	arg1	sites					574:578	2 potential N-glycosylation sites	546:578	2 potential N-glycosylation sites	546:578	The ANITVNITV peptide described by Perlmann and coworkers presents 9 amino acids and 2 potential N-glycosylation sites.
31336133	13	25	theme	IFN4NNter	1881:1889	arg1	biobetter					1909:1917	an IFN-α based biobetter	1894:1917	an IFN-α based biobetter	1894:1917	This feature together with its improved pharmacokinetics encourages the development of IFN4NNter as an IFN-α based biobetter.
31336133	13	25	theme	IFN4NNter	1881:1889	arg1	development					1866:1876	the development	1862:1876	the development of IFN4NNter	1862:1889	This feature together with its improved pharmacokinetics encourages the development of IFN4NNter as an IFN-α based biobetter.
31336133	4	26	theme	protein	673:679	arg1	charge					659:664	negative charge	650:664	negative charge	650:664	Its fusion to FSH resulted in the increase of the molecular mass and negative charge of the protein.
31336133	4	26	theme	protein	673:679	arg1	mass					641:644	molecular mass	631:644	molecular mass	631:644	Its fusion to FSH resulted in the increase of the molecular mass and negative charge of the protein.
31336133	10	27	theme	parental	1565:1572	arg1	molecules					1574:1582	the parental molecules	1561:1582	the parental molecules	1561:1582	However, in vitro antiproliferative SBA was differentially modified for IFNwtNter and IFN4NNter in comparison with the parental molecules.
31336133	6	28	link	N-linked	1038:1045	arg1	glycans					1047:1053	4 N-linked glycans	1036:1053	4 N-linked glycans	1036:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	29	gly	hyperglycosylated	976:992	arg1	IFN4N					1003:1007	IFN4N	1003:1007	IFN4N	1003:1007	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	29	gly	hyperglycosylated	976:992	arg1	variant					994:1000	a hyperglycosylated variant	974:1000	a hyperglycosylated variant (IFN4N)	974:1008	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	3	30	theme	N-glycosylation	558:572	arg1	sites					574:578	2 potential N-glycosylation sites	546:578	2 potential N-glycosylation sites	546:578	The ANITVNITV peptide described by Perlmann and coworkers presents 9 amino acids and 2 potential N-glycosylation sites.
31336133	3	31	theme	ANITVNITV	465:473	arg1	peptide					475:481	The ANITVNITV peptide	461:481	The ANITVNITV peptide described by Perlmann and coworkers	461:517	The ANITVNITV peptide described by Perlmann and coworkers presents 9 amino acids and 2 potential N-glycosylation sites.
31336133	9	32	dep	in	1389:1390	arg1	vitro					1392:1396	vitro	1392:1396	vitro	1392:1396	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	6	33	theme	hIFN-α2b	906:913	arg1	properties					885:894	the physicochemical, biological and pharmacokinetic properties	833:894	the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans	833:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	10	34	theme	in	1455:1456	arg1	SBA					1482:1484	in vitro antiproliferative SBA	1455:1484	in vitro antiproliferative SBA	1455:1484	However, in vitro antiproliferative SBA was differentially modified for IFNwtNter and IFN4NNter in comparison with the parental molecules.
31336133	12	35	theme	IFN4N	1731:1735	arg1	N-terminus					1717:1726	the N-terminus	1713:1726	the N-terminus of IFN4N	1713:1735	Remarkably, the addition of the ANITVNITV peptide to the N-terminus of IFN4N had a positive impact on its growth-inhibitory activity.
31336133	6	36	contain	contains	930:937	arg2	variant					994:1000	a hyperglycosylated variant	974:1000	a hyperglycosylated variant (IFN4N)	974:1008	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	36	contain	contains	930:937	arg1	IFNwt					916:920	IFNwt	916:920	IFNwt	916:920	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	36	contain	contains	930:937	arg1	hIFN-α2b					906:913	native hIFN-α2b	899:913	native hIFN-α2b (IFNwt)	899:921	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	36	contain	contains	930:937	arg2	IFN4N					1003:1007	IFN4N	1003:1007	IFN4N	1003:1007	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	36	contain	contains	930:937	arg2	site					964:967	a single O-glycosylation site	939:967	a single O-glycosylation site	939:967	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	9	37	theme	peptide	1335:1341	arg1	strategy					1350:1357	the synthetic peptide fusion strategy	1321:1357	the synthetic peptide fusion strategy	1321:1357	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	9	38	theme	synthetic	1325:1333	arg1	strategy					1350:1357	the synthetic peptide fusion strategy	1321:1357	the synthetic peptide fusion strategy	1321:1357	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	8	39	theme	pharmacokinetic	1218:1232	arg1	properties					1234:1243	the pharmacokinetic properties	1214:1243	the pharmacokinetic properties of the new molecules	1214:1264	Therefore, the pharmacokinetic properties of the new molecules were significantly improved.
31336133	12	40	theme	positive	1743:1750	arg1	impact					1752:1757	a positive impact	1741:1757	a positive impact	1741:1757	Remarkably, the addition of the ANITVNITV peptide to the N-terminus of IFN4N had a positive impact on its growth-inhibitory activity.
31336133	9	41	theme	antiviral	1398:1406	arg1	SBA					1440:1442	SBA	1440:1442	SBA	1440:1442	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	9	41	theme	antiviral	1398:1406	arg1	activities					1428:1437	their in vitro antiviral specific biological activities	1383:1437	their in vitro antiviral specific biological activities (SBA)	1383:1443	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	0	42	theme	peptide	20:26	arg1	fusion					28:33	ANITVNITV peptide fusion	10:33	ANITVNITV peptide fusion	10:33	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	6	43	theme	hyperglycosylated	976:992	arg1	IFN4N					1003:1007	IFN4N	1003:1007	IFN4N	1003:1007	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	43	theme	hyperglycosylated	976:992	arg1	variant					994:1000	a hyperglycosylated variant	974:1000	a hyperglycosylated variant (IFN4N)	974:1008	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	44	theme	peptide	815:821	arg1	fusion					823:828	ANITVNITV peptide fusion	805:828	ANITVNITV peptide fusion	805:828	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	12	45	contain	had	1737:1739	arg2	impact					1752:1757	a positive impact	1741:1757	a positive impact	1741:1757	Remarkably, the addition of the ANITVNITV peptide to the N-terminus of IFN4N had a positive impact on its growth-inhibitory activity.
31336133	12	45	contain	had	1737:1739	arg1	addition					1676:1683	the addition	1672:1683	the addition of the ANITVNITV peptide to the N-terminus of IFN4N	1672:1735	Remarkably, the addition of the ANITVNITV peptide to the N-terminus of IFN4N had a positive impact on its growth-inhibitory activity.
31336133	2	46	theme	pharmacokinetic	433:447	arg1	properties					449:458	the pharmacokinetic properties	429:458	the pharmacokinetic properties	429:458	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	2	47	theme	properties	449:458	arg1	improvement					414:424	the improvement	410:424	the improvement of the pharmacokinetic properties	410:458	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	9	48	theme	fusion	1343:1348	arg1	strategy					1350:1357	the synthetic peptide fusion strategy	1321:1357	the synthetic peptide fusion strategy	1321:1357	The molecules obtained by the synthetic peptide fusion strategy evidenced a decrease in their in vitro antiviral specific biological activities (SBA).
31336133	0	49	theme	variant	119:125	arg1	pharmacokinetics					58:73	pharmacokinetics	58:73	pharmacokinetics	58:73	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	0	49	theme	variant	119:125	arg1	bioactivity					42:52	bioactivity	42:52	bioactivity	42:52	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	6	50	theme	native	899:904	arg1	IFNwt					916:920	IFNwt	916:920	IFNwt	916:920	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	50	theme	native	899:904	arg1	hIFN-α2b					906:913	native hIFN-α2b	899:913	native hIFN-α2b (IFNwt)	899:921	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	0	51	gly	hyper-N-glycosylated	98:117	arg1	variant					119:125	a hyper-N-glycosylated variant	96:125	a hyper-N-glycosylated variant	96:125	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	6	52	from	influence	792:800	arg1	properties					885:894	the physicochemical, biological and pharmacokinetic properties	833:894	the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans	833:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	13	53	theme	improved	1825:1832	arg1	pharmacokinetics					1834:1849	its improved pharmacokinetics	1821:1849	its improved pharmacokinetics	1821:1849	This feature together with its improved pharmacokinetics encourages the development of IFN4NNter as an IFN-α based biobetter.
31336133	11	54	theme	antiproliferative	1619:1635	arg1	SBA					1637:1639	the antiproliferative SBA	1615:1639	the antiproliferative SBA	1615:1639	For IFNwtNter, a reduction in the antiproliferative SBA was also observed.
31336133	0	55	dep	bioactivity	42:52	arg1	the					38:40	the	38:40	the	38:40	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	10	56	dep	in	1455:1456	arg1	vitro					1458:1462	vitro	1458:1462	vitro	1458:1462	However, in vitro antiproliferative SBA was differentially modified for IFNwtNter and IFN4NNter in comparison with the parental molecules.
31336133	0	57	theme	fusion	28:33	arg1	Effect					0:5	Effect	0:5	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.	0:126	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	7	58	theme	negative	1144:1151	arg1	charge					1153:1158	negative charge	1144:1158	negative charge compared to IFNwt and IFN4N, respectively	1144:1200	The resulting molecules, IFNwtNter and IFN4NNter, evidenced a higher molecular mass and negative charge compared to IFNwt and IFN4N, respectively.
31336133	4	59	theme	charge	659:664	arg1	increase					615:622	the increase	611:622	the increase of the molecular mass and negative charge of the protein	611:679	Its fusion to FSH resulted in the increase of the molecular mass and negative charge of the protein.
31336133	7	60	theme	higher	1118:1123	arg1	mass					1135:1138	a higher molecular mass	1116:1138	a higher molecular mass	1116:1138	The resulting molecules, IFNwtNter and IFN4NNter, evidenced a higher molecular mass and negative charge compared to IFNwt and IFN4N, respectively.
31336133	1	61	dep	in	239:240	arg1	vivo					242:245	vivo	242:245	vivo	242:245	Different strategies have been developed and successfully applied to biotherapeutics in order to improve their in vivo efficacy.
31336133	7	62	theme	molecular	1125:1133	arg1	mass					1135:1138	a higher molecular mass	1116:1138	a higher molecular mass	1116:1138	The resulting molecules, IFNwtNter and IFN4NNter, evidenced a higher molecular mass and negative charge compared to IFNwt and IFN4N, respectively.
31336133	6	63	theme	O-glycosylation	948:962	arg1	site					964:967	a single O-glycosylation site	939:967	a single O-glycosylation site	939:967	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	4	64	dep	mass	641:644	arg1	the					627:629	the	627:629	the	627:629	Its fusion to FSH resulted in the increase of the molecular mass and negative charge of the protein.
31336133	6	65	theme	biological	854:863	arg1	properties					885:894	the physicochemical, biological and pharmacokinetic properties	833:894	the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans	833:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	66	theme	single	941:946	arg1	site					964:967	a single O-glycosylation site	939:967	a single O-glycosylation site	939:967	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	67	theme	ANITVNITV	805:813	arg1	fusion					823:828	ANITVNITV peptide fusion	805:828	ANITVNITV peptide fusion	805:828	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	6	68	theme	study	767:771	arg1	aim					748:750	The aim	744:750	The aim of the present study	744:771	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	1	69	theme	Different	128:136	arg1	strategies					138:147	Different strategies	128:147	Different strategies	128:147	Different strategies have been developed and successfully applied to biotherapeutics in order to improve their in vivo efficacy.
31336133	8	70	theme	molecules	1256:1264	arg1	properties					1234:1243	the pharmacokinetic properties	1214:1243	the pharmacokinetic properties of the new molecules	1214:1264	Therefore, the pharmacokinetic properties of the new molecules were significantly improved.
31336133	7	71	theme	resulting	1060:1068	arg1	IFNwtNter					1081:1089	IFNwtNter	1081:1089	IFNwtNter	1081:1089	The resulting molecules, IFNwtNter and IFN4NNter, evidenced a higher molecular mass and negative charge compared to IFNwt and IFN4N, respectively.
31336133	7	71	theme	resulting	1060:1068	arg1	molecules					1070:1078	The resulting molecules	1056:1078	The resulting molecules	1056:1078	The resulting molecules, IFNwtNter and IFN4NNter, evidenced a higher molecular mass and negative charge compared to IFNwt and IFN4N, respectively.
31336133	7	71	theme	resulting	1060:1068	arg1	IFN4NNter					1095:1103	IFN4NNter	1095:1103	IFN4NNter	1095:1103	The resulting molecules, IFNwtNter and IFN4NNter, evidenced a higher molecular mass and negative charge compared to IFNwt and IFN4N, respectively.
31336133	2	72	theme	genetic	261:267	arg1	fusion					269:274	The genetic fusion	257:274	The genetic fusion to natural or synthetic glycosylated peptides	257:320	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	6	73	theme	present	759:765	arg1	study					767:771	the present study	755:771	the present study	755:771	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	2	74	theme	promising	336:344	arg1	strategy					346:353	a promising strategy	334:353	a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties	334:458	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	1	75	theme	in	239:240	arg1	efficacy					247:254	their in vivo efficacy	233:254	their in vivo efficacy	233:254	Different strategies have been developed and successfully applied to biotherapeutics in order to improve their in vivo efficacy.
31336133	6	76	theme	physicochemical	837:851	arg1	properties					885:894	the physicochemical, biological and pharmacokinetic properties	833:894	the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans	833:1053	The aim of the present study was to compare the influence of ANITVNITV peptide fusion on the physicochemical, biological and pharmacokinetic properties of native hIFN-α2b (IFNwt), which contains a single O-glycosylation site, and a hyperglycosylated variant (IFN4N), that bears, in addition, 4 N-linked glycans.
31336133	13	77	theme	IFN-α	1897:1901	arg1	biobetter					1909:1917	an IFN-α based biobetter	1894:1917	an IFN-α based biobetter	1894:1917	This feature together with its improved pharmacokinetics encourages the development of IFN4NNter as an IFN-α based biobetter.
31336133	13	77	theme	IFN-α	1897:1901	arg1	development					1866:1876	the development	1862:1876	the development of IFN4NNter	1862:1889	This feature together with its improved pharmacokinetics encourages the development of IFN4NNter as an IFN-α based biobetter.
31336133	4	78	theme	negative	650:657	arg1	charge					659:664	negative charge	650:664	negative charge	650:664	Its fusion to FSH resulted in the increase of the molecular mass and negative charge of the protein.
31336133	2	79	dep	natural	279:285	arg1	peptides					313:320	glycosylated peptides	300:320	glycosylated peptides	300:320	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	4	80	theme	mass	641:644	arg1	increase					615:622	the increase	611:622	the increase of the molecular mass and negative charge of the protein	611:679	Its fusion to FSH resulted in the increase of the molecular mass and negative charge of the protein.
31336133	0	81	theme	ANITVNITV	10:18	arg1	fusion					28:33	ANITVNITV peptide fusion	10:33	ANITVNITV peptide fusion	10:33	Effect of ANITVNITV peptide fusion on the bioactivity and pharmacokinetics of human IFN-α2b and a hyper-N-glycosylated variant.
31336133	2	82	theme	protein	378:384	arg1	sequence					386:393	the protein sequence	374:393	the protein sequence	374:393	The genetic fusion to natural or synthetic glycosylated peptides constitutes a promising strategy since it conserves the protein sequence and results in the improvement of the pharmacokinetic properties.
31336133	11	83	from	reduction	1602:1610	arg1	SBA					1637:1639	the antiproliferative SBA	1615:1639	the antiproliferative SBA	1615:1639	For IFNwtNter, a reduction in the antiproliferative SBA was also observed.
31336133	4	84	theme	molecular	631:639	arg1	mass					641:644	molecular mass	631:644	molecular mass	631:644	Its fusion to FSH resulted in the increase of the molecular mass and negative charge of the protein.
31316108	8	0	from	cells	1395:1399	arg1	half					1355:1358	less than half	1345:1358	less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment	1345:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	1	1	theme	glycoproteins	251:263	arg1	modification					226:237	post-translation modification	209:237	post-translation modification of N-linked glycoproteins	209:263	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	1	2	link	N-linked	242:249	arg1	glycoproteins					251:263	N-linked glycoproteins	242:263	N-linked glycoproteins	242:263	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	3	3	theme	metastatic	518:527	arg1	potential					529:537	metastatic potential	518:537	metastatic potential	518:537	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	3	4	from	role	487:490	arg1	potential					529:537	metastatic potential	518:537	metastatic potential	518:537	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	3	4	from	role	487:490	arg1	activity					587:594	receptor tyrosine kinases (RTKs) signaling activity	544:594	receptor tyrosine kinases (RTKs) signaling activity	544:594	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	3	4	from	role	487:490	arg1	growth					510:515	cell growth	505:515	cell growth	505:515	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	3	5	theme	kinases	562:568	arg1	activity					587:594	receptor tyrosine kinases (RTKs) signaling activity	544:594	receptor tyrosine kinases (RTKs) signaling activity	544:594	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	1	6	mod	modification	226:237	arg1	glycoproteins					251:263	N-linked glycoproteins	242:263	N-linked glycoproteins	242:263	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	1	6	mod	modification	226:237	arg3	post-translation					209:224	post-translation modification	209:237	post-translation modification of N-linked glycoproteins	209:263	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	3	7	theme	receptor	544:551	arg1	RTKs					571:574	RTKs	571:574	RTKs	571:574	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	3	7	theme	receptor	544:551	arg1	kinases					562:568	receptor tyrosine kinases	544:568	receptor tyrosine kinases (RTKs) signaling activity	544:594	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	5	8	theme	transfected	820:830	arg1	cells					832:836	non-target transfected cells	809:836	non-target transfected cells	809:836	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	4	9	theme	CRISPR-CAS9	626:636	arg1	technology					638:647	CRISPR-CAS9 technology	626:647	CRISPR-CAS9 technology	626:647	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	0	10	theme	tyrosine	125:132	arg1	activities					141:150	receptor tyrosine kinase activities	116:150	receptor tyrosine kinase activities	116:150	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	3	11	theme	signaling	577:585	arg1	activity					587:594	receptor tyrosine kinases (RTKs) signaling activity	544:594	receptor tyrosine kinases (RTKs) signaling activity	544:594	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	4	12	used	used	653:656	arg2	technology					638:647	CRISPR-CAS9 technology	626:647	CRISPR-CAS9 technology	626:647	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	8	13	theme	tumor	1471:1475	arg1	cells					1477:1481	tumor cells	1471:1481	tumor cells in an effort to improve lung cancer treatment	1471:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	8	14	theme	RTK	1317:1319	arg1	activities					1331:1340	overall RTK signaling activities	1309:1340	overall RTK signaling activities	1309:1340	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	3	15	theme	carcinoma	604:612	arg1	lines					619:623	lung carcinoma cell lines	599:623	lung carcinoma cell lines	599:623	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	8	16	theme	less	1345:1348	arg1	half					1355:1358	less than half	1345:1358	less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment	1345:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	5	17	theme	GluIIβ	728:733	arg1	cells					744:748	GluIIβ knockout cells	728:748	GluIIβ knockout cells	728:748	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	7	18	theme	lung	1188:1191	arg1	cells					1200:1204	lung cancer cells	1188:1204	lung cancer cells	1188:1204	Knockout of GluIIβ increased the sensitivity of lung cancer cells to cisplatin but reduced their sensitivity to gefitinib.
31316108	5	19	theme	fetal	881:885	arg1	serum					894:898	fetal bovine serum	881:898	fetal bovine serum	881:898	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	4	20	theme	encoding	681:688	arg1	PRKSH					696:700	PRKSH	696:700	PRKSH	696:700	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	4	20	theme	encoding	681:688	arg1	gene					690:693	the GluIIβ encoding gene	670:693	the GluIIβ encoding gene (PRKSH)	670:701	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	5	21	theme	serum	894:898	arg1	concentrations					863:876	lower concentrations	857:876	lower concentrations of fetal bovine serum	857:898	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	8	22	theme	cancer	1512:1517	arg1	treatment					1519:1527	lung cancer treatment	1507:1527	lung cancer treatment	1507:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	8	23	theme	those	1363:1367	arg1	half					1355:1358	less than half	1345:1358	less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment	1345:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	0	24	theme	lung	84:87	arg1	cells					96:100	lung cancer cells	84:100	lung cancer cells	84:100	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	5	25	theme	nutritional	957:967	arg1	deprivation					969:979	nutritional deprivation	957:979	nutritional deprivation	957:979	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	6	26	theme	Cell	982:985	arg1	components					1047:1056	the fundamental components	1031:1056	the fundamental components of cancer cell metastasis	1031:1082	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	6	26	theme	Cell	982:985	arg1	migration					987:995	Cell migration	982:995	Cell migration	982:995	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	8	27	theme	non-target	1372:1381	arg1	cells					1395:1399	non-target transfected cells	1372:1399	non-target transfected cells	1372:1399	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	2	28	theme	tumor	390:394	arg1	tissues					396:402	lung tumor tissues	385:402	lung tumor tissues	385:402	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	0	29	theme	cells	96:100	arg1	potential					71:79	metastatic potential	60:79	metastatic potential	60:79	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	0	29	theme	cells	96:100	arg1	growth					49:54	growth	49:54	growth	49:54	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	8	30	from	half	1355:1358	arg1	cells					1395:1399	non-target transfected cells	1372:1399	non-target transfected cells	1372:1399	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	8	31	from	cells	1477:1481	arg1	effort					1489:1494	an effort to improve lung cancer treatment	1486:1527	an effort to improve lung cancer treatment	1486:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	4	32	theme	lung	706:709	arg1	cells					721:725	lung carcinoma cells	706:725	lung carcinoma cells	706:725	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	0	33	theme	Knockout	0:7	arg1	subunit					32:38	Knockout of glucosidase II beta subunit	0:38	Knockout of glucosidase II beta subunit	0:38	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	5	34	theme	ability	932:938	arg1	impairment					912:921	impairment	912:921	impairment of their ability to survive under nutritional deprivation	912:979	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	6	35	theme	metastasis	1073:1082	arg1	components					1047:1056	the fundamental components	1031:1056	the fundamental components of cancer cell metastasis	1031:1082	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	6	35	theme	metastasis	1073:1082	arg1	migration					987:995	Cell migration	982:995	Cell migration	982:995	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	5	36	with	cells	832:836	arg1	concentrations					863:876	lower concentrations	857:876	lower concentrations of fetal bovine serum	857:898	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	0	37	theme	glucosidase	12:22	arg1	Knockout					0:7	Knockout	0:7	Knockout	0:7	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	6	38	theme	cancer	1061:1066	arg1	metastasis					1073:1082	cancer cell metastasis	1061:1082	cancer cell metastasis	1061:1082	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	7	39	theme	cells	1200:1204	arg1	sensitivity					1173:1183	the sensitivity	1169:1183	the sensitivity of lung cancer cells to cisplatin	1169:1217	Knockout of GluIIβ increased the sensitivity of lung cancer cells to cisplatin but reduced their sensitivity to gefitinib.
31316108	0	40	theme	beta	27:30	arg1	subunit					32:38	Knockout of glucosidase II beta subunit	0:38	Knockout of glucosidase II beta subunit	0:38	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	8	41	theme	novel	1426:1430	arg1	strategy					1432:1439	a novel strategy	1424:1439	a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment	1424:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	5	42	theme	growth	779:784	arg1	rates					786:790	drastically slower growth rates	760:790	drastically slower growth rates	760:790	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	5	43	dep	cells	832:836	arg1	comparison					795:804	comparison	795:804	comparison	795:804	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	2	44	theme	beta	332:335	arg1	subunit					337:343	glucosidase II beta subunit	317:343	glucosidase II beta subunit (GluIIβ)	317:352	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	2	44	theme	beta	332:335	arg1	GluIIβ					346:351	GluIIβ	346:351	GluIIβ	346:351	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	8	45	theme	multiple	1454:1461	arg1	RTKs					1463:1466	multiple RTKs	1454:1466	multiple RTKs	1454:1466	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	3	46	theme	cell	505:508	arg1	growth					510:515	cell growth	505:515	cell growth	505:515	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	7	47	theme	GluIIβ	1152:1157	arg1	Knockout					1140:1147	Knockout	1140:1147	Knockout	1140:1147	Knockout of GluIIβ increased the sensitivity of lung cancer cells to cisplatin but reduced their sensitivity to gefitinib.
31316108	6	48	theme	GluIIβ	1117:1122	arg1	cells					1133:1137	GluIIβ knockout cells	1117:1137	GluIIβ knockout cells	1117:1137	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	3	49	theme	GluIIβ	495:500	arg1	role					487:490	the role	483:490	the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines	483:623	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	1	50	theme	N-linked	242:249	arg1	glycoproteins					251:263	N-linked glycoproteins	242:263	N-linked glycoproteins	242:263	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	4	51	from	knockout	661:668	arg1	cells					721:725	lung carcinoma cells	706:725	lung carcinoma cells	706:725	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	3	52	theme	tyrosine	553:560	arg1	RTKs					571:574	RTKs	571:574	RTKs	571:574	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	3	52	theme	tyrosine	553:560	arg1	kinases					562:568	receptor tyrosine kinases	544:568	receptor tyrosine kinases (RTKs) signaling activity	544:594	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	3	53	from	growth	510:515	arg1	lines					619:623	lung carcinoma cell lines	599:623	lung carcinoma cell lines	599:623	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	2	54	theme	glucosidase	317:327	arg1	subunit					337:343	glucosidase II beta subunit	317:343	glucosidase II beta subunit (GluIIβ)	317:352	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	2	54	theme	glucosidase	317:327	arg1	GluIIβ					346:351	GluIIβ	346:351	GluIIβ	346:351	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	5	55	theme	lower	857:861	arg1	concentrations					863:876	lower concentrations	857:876	lower concentrations of fetal bovine serum	857:898	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	0	56	theme	receptor	116:123	arg1	activities					141:150	receptor tyrosine kinase activities	116:150	receptor tyrosine kinase activities	116:150	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	5	57	theme	non-target	809:818	arg1	cells					832:836	non-target transfected cells	809:836	non-target transfected cells	809:836	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	8	58	theme	than	1350:1353	arg1	half					1355:1358	less than half	1345:1358	less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment	1345:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	0	59	theme	kinase	134:139	arg1	activities					141:150	receptor tyrosine kinase activities	116:150	receptor tyrosine kinase activities	116:150	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	8	60	theme	overall	1309:1315	arg1	activities					1331:1340	overall RTK signaling activities	1309:1340	overall RTK signaling activities	1309:1340	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	3	61	theme	lung	599:602	arg1	lines					619:623	lung carcinoma cell lines	599:623	lung carcinoma cell lines	599:623	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	6	62	theme	fundamental	1035:1045	arg1	components					1047:1056	the fundamental components	1031:1056	the fundamental components of cancer cell metastasis	1031:1082	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	6	62	theme	fundamental	1035:1045	arg1	migration					987:995	Cell migration	982:995	Cell migration	982:995	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	8	63	theme	signaling	1321:1329	arg1	activities					1331:1340	overall RTK signaling activities	1309:1340	overall RTK signaling activities	1309:1340	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	0	64	theme	metastatic	60:69	arg1	potential					71:79	metastatic potential	60:79	metastatic potential	60:79	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	8	65	theme	lung	1507:1510	arg1	cancer					1512:1517	lung cancer	1507:1517	lung cancer treatment	1507:1527	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	5	66	theme	knockout	735:742	arg1	cells					744:748	GluIIβ knockout cells	728:748	GluIIβ knockout cells	728:748	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	5	67	theme	bovine	887:892	arg1	serum					894:898	fetal bovine serum	881:898	fetal bovine serum	881:898	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	6	68	theme	anchorage-independent	1001:1021	arg1	growth					1023:1028	anchorage-independent growth	1001:1028	anchorage-independent growth	1001:1028	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	4	69	theme	GluIIβ	674:679	arg1	PRKSH					696:700	PRKSH	696:700	PRKSH	696:700	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	4	69	theme	GluIIβ	674:679	arg1	gene					690:693	the GluIIβ encoding gene	670:693	the GluIIβ encoding gene (PRKSH)	670:701	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	3	70	from	potential	529:537	arg1	lines					619:623	lung carcinoma cell lines	599:623	lung carcinoma cell lines	599:623	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	0	71	theme	cancer	89:94	arg1	cells					96:100	lung cancer cells	84:100	lung cancer cells	84:100	Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities.
31316108	3	72	from	activity	587:594	arg1	lines					619:623	lung carcinoma cell lines	599:623	lung carcinoma cell lines	599:623	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	1	73	theme	major	184:188	arg1	role					190:193	a major role	182:193	a major role	182:193	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	2	74	theme	lung	385:388	arg1	tissues					396:402	lung tumor tissues	385:402	lung tumor tissues	385:402	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	7	75	theme	cancer	1193:1198	arg1	cells					1200:1204	lung cancer cells	1188:1204	lung cancer cells	1188:1204	Knockout of GluIIβ increased the sensitivity of lung cancer cells to cisplatin but reduced their sensitivity to gefitinib.
31316108	8	76	theme	transfected	1383:1393	arg1	cells					1395:1399	non-target transfected cells	1372:1399	non-target transfected cells	1372:1399	Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
31316108	6	77	theme	cell	1068:1071	arg1	metastasis					1073:1082	cancer cell metastasis	1061:1082	cancer cell metastasis	1061:1082	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
31316108	4	78	theme	carcinoma	711:719	arg1	cells					721:725	lung carcinoma cells	706:725	lung carcinoma cells	706:725	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	4	79	from	cells	721:725	arg1	knockout					661:668	knockout	661:668	knockout	661:668	CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells.
31316108	3	80	theme	cell	614:617	arg1	lines					619:623	lung carcinoma cell lines	599:623	lung carcinoma cell lines	599:623	Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines.
31316108	5	81	theme	slower	772:777	arg1	rates					786:790	drastically slower growth rates	760:790	drastically slower growth rates	760:790	GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation.
31316108	2	82	theme	subunit	337:343	arg1	expression					303:312	the expression	299:312	the expression of glucosidase II beta subunit (GluIIβ)	299:352	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	1	83	gly	glycoproteins	251:263	arg1	glycoproteins					251:263	N-linked glycoproteins	242:263	N-linked glycoproteins	242:263	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	2	84	theme	II	329:330	arg1	subunit					337:343	glucosidase II beta subunit	317:343	glucosidase II beta subunit (GluIIβ)	317:352	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	2	84	theme	II	329:330	arg1	GluIIβ					346:351	GluIIβ	346:351	GluIIβ	346:351	We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis.
31316108	1	85	theme	post-translation	209:224	arg1	modification					226:237	post-translation modification	209:237	post-translation modification of N-linked glycoproteins	209:263	Glucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins.
31316108	6	86	theme	knockout	1124:1131	arg1	cells					1133:1137	GluIIβ knockout cells	1117:1137	GluIIβ knockout cells	1117:1137	Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells.
30242111	4	0	theme	falciparum-infected	765:783	arg1	placentas					785:793	past P. falciparum-infected placentas	757:793	past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	757:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	2	1	theme	birth	402:406	arg1	weight					408:413	low birth weight	398:413	low birth weight because of fetal growth restriction	398:449	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	2	from	cells	200:204	arg1	placenta					213:220	the placenta	209:220	the placenta	209:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	3	theme	low	398:400	arg1	weight					408:413	low birth weight	398:413	low birth weight because of fetal growth restriction	398:449	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	4	from	folding	1056:1062	arg1	placentas					1109:1117	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	6	5	theme	adverse	1419:1425	arg1	outcomes					1437:1444	adverse pregnancy outcomes	1419:1444	adverse pregnancy outcomes	1419:1444	This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.
30242111	2	6	from	placenta	213:220	arg1	levels					236:241	increased levels	226:241	increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes	226:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	6	from	placenta	213:220	arg1	Accumulation					168:179	Accumulation	168:179	Accumulation of maternal immune cells in the placenta	168:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	7	theme	increased	1231:1239	arg1	apoptosis					1241:1249	an increased apoptosis	1228:1249	an increased apoptosis in past-infected placentas	1228:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	8	from	apoptosis	1241:1249	arg1	placentas					1268:1276	past-infected placentas	1254:1276	past-infected placentas	1254:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	9	theme	protein	1048:1054	arg1	folding					1056:1062	protein folding	1048:1062	protein folding	1048:1062	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	10	theme	oxidative	1030:1038	arg1	stress					1040:1045	oxidative stress	1030:1045	oxidative stress	1030:1045	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	4	11	theme	placental	844:852	arg1	malaria					854:860	placental malaria	844:860	placental malaria	844:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	6	12	theme	therapeutic	1392:1402	arg1	target					1404:1409	therapeutic target	1392:1409	therapeutic target against adverse pregnancy outcomes	1392:1444	This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.
30242111	6	12	theme	therapeutic	1392:1402	arg1	malaria					1352:1358	placental malaria	1342:1358	placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes	1342:1444	This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.
30242111	2	13	theme	erythrocytes	327:338	arg1	sequestration					279:291	sequestration	279:291	sequestration of Plasmodium falciparum-infected erythrocytes	279:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	4	14	from	analysis	745:752	arg1	placentas					785:793	past P. falciparum-infected placentas	757:793	past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	757:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	1	15	theme	malaria-endemic	145:159	arg1	areas					161:165	malaria-endemic areas	145:165	malaria-endemic areas	145:165	Malaria in pregnancy is a public health concern in malaria-endemic areas.
30242111	4	16	theme	P.	762:763	arg1	placentas					785:793	past P. falciparum-infected placentas	757:793	past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	757:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	5	17	theme	overrepresented	993:1007	arg1	processes					1009:1017	overrepresented processes	993:1017	overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	993:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	18	dep	placentas	1109:1117	arg1	correlated					1214:1223	correlated	1214:1223	were further correlated to an increased apoptosis in past-infected placentas	1201:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	2	19	theme	falciparum-infected	307:325	arg1	erythrocytes					327:338	Plasmodium falciparum-infected erythrocytes	296:338	Plasmodium falciparum-infected erythrocytes	296:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	20	from	levels	236:241	arg1	placenta					213:220	the placenta	209:220	the placenta	209:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	21	theme	restriction	439:449	arg1	weight					408:413	low birth weight	398:413	low birth weight because of fetal growth restriction	398:449	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	22	theme	proteins	879:886	arg1	total					865:869	A total	863:869	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites	863:934	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	2	23	theme	Plasmodium	296:305	arg1	erythrocytes					327:338	Plasmodium falciparum-infected erythrocytes	296:338	Plasmodium falciparum-infected erythrocytes	296:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	24	from	apoptosis	1082:1090	arg1	placentas					1109:1117	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	2	25	theme	growth	432:437	arg1	restriction					439:449	fetal growth restriction	426:449	fetal growth restriction	426:449	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	26	theme	poor	364:367	arg1	weight					408:413	low birth weight	398:413	low birth weight because of fetal growth restriction	398:449	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	26	theme	poor	364:367	arg1	outcomes					378:385	poor neonatal outcomes	364:385	poor neonatal outcomes	364:385	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	27	theme	fetal	426:430	arg1	restriction					439:449	fetal growth restriction	426:449	fetal growth restriction	426:449	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	0	28	theme	Integrated	0:9	arg1	Proteomics					11:20	Integrated Proteomics	0:20	Integrated Proteomics	0:20	Integrated Proteomics Reveals Apoptosis-related Mechanisms Associated with Placental Malaria.
30242111	5	29	dep	AKT	1129:1131	arg1	activation					1160:1169	activation	1160:1169	activation	1160:1169	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	3	30	theme	pharmacological	630:644	arg1	treatment					646:654	pharmacological treatment	630:654	pharmacological treatment	630:654	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	4	31	theme	glycoproteome	731:743	arg1	analysis					745:752	an integrated proteome, phosphoproteome and glycoproteome analysis	687:752	an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	687:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	0	32	theme	Apoptosis-related	30:46	arg1	Mechanisms					48:57	Apoptosis-related Mechanisms	30:57	Apoptosis-related Mechanisms Associated with Placental Malaria	30:91	Integrated Proteomics Reveals Apoptosis-related Mechanisms Associated with Placental Malaria.
30242111	5	33	theme	clinical	1186:1193	arg1	data					1195:1198	clinical data	1186:1198	clinical data	1186:1198	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	1	34	from	concern	134:140	arg1	areas					161:165	malaria-endemic areas	145:165	malaria-endemic areas	145:165	Malaria in pregnancy is a public health concern in malaria-endemic areas.
30242111	5	35	theme	ERK	1137:1139	arg1	pathways					1151:1158	ERK signaling pathways	1137:1158	ERK signaling pathways	1137:1158	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	3	36	theme	past	657:660	arg1	infection					662:670	past infection	657:670	past infection	657:670	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	4	37	theme	integrated	690:699	arg1	analysis					745:752	an integrated proteome, phosphoproteome and glycoproteome analysis	687:752	an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	687:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	4	38	theme	molecular	810:818	arg1	changes					820:826	molecular changes	810:826	molecular changes associated with placental malaria	810:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	6	39	theme	apoptosis-related	1297:1313	arg1	mechanisms					1315:1324	apoptosis-related mechanisms	1297:1324	apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes	1297:1444	This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.
30242111	1	40	theme	public	120:125	arg1	Malaria					94:100	Malaria	94:100	Malaria in pregnancy	94:113	Malaria in pregnancy is a public health concern in malaria-endemic areas.
30242111	1	40	theme	public	120:125	arg1	concern					134:140	a public health concern	118:140	a public health concern in malaria-endemic areas	118:165	Malaria in pregnancy is a public health concern in malaria-endemic areas.
30242111	3	41	theme	P.	511:512	arg1	placenta					534:541	a P. falciparum-infected placenta	509:541	a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection)	509:671	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	5	42	from	placentas	1109:1117	arg1	regulation					1068:1077	regulation	1068:1077	regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1068:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	42	from	placentas	1109:1117	arg1	stress					1040:1045	oxidative stress	1030:1045	oxidative stress	1030:1045	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	42	from	placentas	1109:1117	arg1	folding					1056:1062	protein folding	1048:1062	protein folding	1048:1062	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	2	43	theme	cells	200:204	arg1	levels					236:241	increased levels	226:241	increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes	226:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	43	theme	cells	200:204	arg1	Accumulation					168:179	Accumulation	168:179	Accumulation of maternal immune cells in the placenta	168:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	44	theme	cytokines	259:267	arg1	levels					236:241	increased levels	226:241	increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes	226:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	44	theme	cytokines	259:267	arg1	Accumulation					168:179	Accumulation	168:179	Accumulation of maternal immune cells in the placenta	168:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	45	from	stress	1040:1045	arg1	placentas					1109:1117	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	46	theme	phosphosites	923:934	arg1	total					865:869	A total	863:869	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites	863:934	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	3	47	theme	molecular	478:486	arg1	changes					488:494	the molecular changes	474:494	the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection)	474:671	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	2	48	theme	immune	193:198	arg1	cells					200:204	maternal immune cells	184:204	maternal immune cells in the placenta	184:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	49	theme	inflammatory	246:257	arg1	cytokines					259:267	inflammatory cytokines	246:267	inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes	246:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	4	50	theme	proteome	701:708	arg1	analysis					745:752	an integrated proteome, phosphoproteome and glycoproteome analysis	687:752	an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	687:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	0	51	theme	Placental	75:83	arg1	Malaria					85:91	Placental Malaria	75:91	Placental Malaria	75:91	Integrated Proteomics Reveals Apoptosis-related Mechanisms Associated with Placental Malaria.
30242111	2	52	theme	maternal	184:191	arg1	cells					200:204	maternal immune cells	184:204	maternal immune cells in the placenta	184:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	53	gly	glycosites	903:912	arg2	glycosites					903:912	1733 N-linked glycosites	889:912	1733 N-linked glycosites	889:912	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	1	54	theme	health	127:132	arg1	Malaria					94:100	Malaria	94:100	Malaria in pregnancy	94:113	Malaria in pregnancy is a public health concern in malaria-endemic areas.
30242111	1	54	theme	health	127:132	arg1	concern					134:140	a public health concern	118:140	a public health concern in malaria-endemic areas	118:165	Malaria in pregnancy is a public health concern in malaria-endemic areas.
30242111	2	55	from	Accumulation	168:179	arg1	placenta					213:220	the placenta	209:220	the placenta	209:220	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	56	theme	past-infected	1254:1266	arg1	placentas					1268:1276	past-infected placentas	1254:1276	past-infected placentas	1254:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	2	57	theme	increased	226:234	arg1	levels					236:241	increased levels	226:241	increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes	226:338	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	58	theme	N-linked	894:901	arg1	glycosites					903:912	1733 N-linked glycosites	889:912	1733 N-linked glycosites	889:912	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	3	59	theme	placental	562:570	arg1	malaria					572:578	placental malaria	562:578	placental malaria	562:578	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	6	60	theme	placental	1342:1350	arg1	malaria					1352:1358	placental malaria	1342:1358	placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes	1342:1444	This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.
30242111	6	60	theme	placental	1342:1350	arg1	target					1404:1409	therapeutic target	1392:1409	therapeutic target against adverse pregnancy outcomes	1392:1444	This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.
30242111	3	61	contain	had	601:603	arg1	placenta					534:541	a P. falciparum-infected placenta	509:541	a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection)	509:671	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	3	61	contain	had	601:603	arg2	parasites					609:617	the parasites	605:617	the parasites cleared by pharmacological treatment	605:654	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	5	62	theme	signaling	1141:1149	arg1	pathways					1151:1158	ERK signaling pathways	1137:1158	ERK signaling pathways	1137:1158	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	63	link	N-linked	894:901	arg1	glycosites					903:912	1733 N-linked glycosites	889:912	1733 N-linked glycosites	889:912	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	3	64	theme	falciparum-infected	514:532	arg1	placenta					534:541	a P. falciparum-infected placenta	509:541	a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection)	509:671	Little is known about the molecular changes occurring in a P. falciparum-infected placenta that has developed placental malaria during pregnancy but had the parasites cleared by pharmacological treatment (past infection).
30242111	6	65	theme	pregnancy	1427:1435	arg1	outcomes					1437:1444	adverse pregnancy outcomes	1419:1444	adverse pregnancy outcomes	1419:1444	This study showed apoptosis-related mechanisms associated with placental malaria that can be further explored as therapeutic target against adverse pregnancy outcomes.
30242111	2	66	theme	neonatal	369:376	arg1	weight					408:413	low birth weight	398:413	low birth weight because of fetal growth restriction	398:449	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	2	66	theme	neonatal	369:376	arg1	outcomes					378:385	poor neonatal outcomes	364:385	poor neonatal outcomes	364:385	Accumulation of maternal immune cells in the placenta and increased levels of inflammatory cytokines caused by sequestration of Plasmodium falciparum-infected erythrocytes have been associated to poor neonatal outcomes, including low birth weight because of fetal growth restriction.
30242111	5	67	theme	related	1019:1025	arg1	processes					1009:1017	overrepresented processes	993:1017	overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	993:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	68	theme	past-infected	1095:1107	arg1	placentas					1109:1117	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	69	from	regulation	1068:1077	arg1	placentas					1109:1117	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1095:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	4	70	theme	past	757:760	arg1	placentas					785:793	past P. falciparum-infected placentas	757:793	past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	757:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	4	71	theme	phosphoproteome	711:725	arg1	analysis					745:752	an integrated proteome, phosphoproteome and glycoproteome analysis	687:752	an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria	687:860	We conducted an integrated proteome, phosphoproteome and glycoproteome analysis in past P. falciparum-infected placentas aiming to find molecular changes associated with placental malaria.
30242111	5	72	theme	apoptosis	1082:1090	arg1	regulation					1068:1077	regulation	1068:1077	regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas	1068:1276	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	72	theme	apoptosis	1082:1090	arg1	stress					1040:1045	oxidative stress	1030:1045	oxidative stress	1030:1045	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	72	theme	apoptosis	1082:1090	arg1	folding					1056:1062	protein folding	1048:1062	protein folding	1048:1062	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	5	73	theme	glycosites	903:912	arg1	total					865:869	A total	863:869	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites	863:934	A total of 2946 proteins, 1733 N-linked glycosites and 4100 phosphosites were identified and quantified in this study, disclosing overrepresented processes related to oxidative stress, protein folding and regulation of apoptosis in past-infected placentas Moreover, AKT and ERK signaling pathways activation, together with clinical data, were further correlated to an increased apoptosis in past-infected placentas.
30242111	1	74	from	Malaria	94:100	arg1	pregnancy					105:113	pregnancy	105:113	pregnancy	105:113	Malaria in pregnancy is a public health concern in malaria-endemic areas.
29342358	0	0	theme	Virus	83:87	arg1	Polymerase					94:103	Hepatitis C Virus NS5B Polymerase	71:103	Hepatitis C Virus NS5B Polymerase	71:103	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	3	1	theme	preclinical	694:704	arg1	species					706:712	preclinical species	694:712	preclinical species	694:712	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	0	2	theme	C	81:81	arg1	Virus					83:87	Hepatitis C Virus	71:87	Hepatitis C Virus NS5B Polymerase	71:103	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	0	3	theme	Oral	162:165	arg1	Bioavailability					167:181	Good Oral Bioavailability	157:181	Good Oral Bioavailability	157:181	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	5	4	theme	once-daily	883:892	arg1	dosing					899:904	once-daily oral dosing	883:904	once-daily oral dosing with ABT-072 in HCV infected patients	883:942	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	0	5	with	Analog	145:150	arg1	Bioavailability					167:181	Good Oral Bioavailability	157:181	Good Oral Bioavailability	157:181	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	3	6	theme	compound	602:609	arg1	permeability					611:622	improved compound permeability	593:622	improved compound permeability	593:622	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	0	7	theme	Polymerase	94:103	arg1	Inhibitors					57:66	Aryl Uracil Inhibitors	45:66	Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase	45:103	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	3	8	theme	better	657:662	arg1	properties					680:689	much better pharmacokinetic properties	652:689	much better pharmacokinetic properties	652:689	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	4	9	theme	genotype	808:815	arg1	assay					828:832	the genotype 1 replicon assay	804:832	the genotype 1 replicon assay	804:832	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	0	10	theme	NS5B	89:92	arg1	Polymerase					94:103	Hepatitis C Virus NS5B Polymerase	71:103	Hepatitis C Virus NS5B Polymerase	71:103	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	4	11	from	1	751:751	arg1	Replacement					715:725	Replacement	715:725	Replacement of the dihydrouracil in 1 with an N-linked uracil	715:775	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	6	12	theme	clinical	955:962	arg1	study					964:968	A phase 2 clinical study	945:968	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450	945:1030	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11 patients who received treatment.
29342358	4	13	theme	replicon	819:826	arg1	assay					828:832	the genotype 1 replicon assay	804:832	the genotype 1 replicon assay	804:832	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	2	14	theme	original	449:456	arg1	inhibitor					464:472	inhibitor 1	464:474	inhibitor 1	464:474	This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication.
29342358	2	14	theme	original	449:456	arg1	lead					458:461	an original lead	446:461	an original lead	446:461	This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication.
29342358	4	15	from	dihydrouracil	734:746	arg1	1					751:751	1	751:751	1	751:751	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	6	16	theme	virologic	1053:1061	arg1	response					1063:1070	a sustained virologic response	1041:1070	a sustained virologic response	1041:1070	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11 patients who received treatment.
29342358	1	17	theme	HCV	352:354	arg1	infection					356:364	HCV infection	352:364	HCV infection	352:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	5	18	theme	infected	926:933	arg1	patients					935:942	HCV infected patients	922:942	HCV infected patients	922:942	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	6	19	theme	sustained	1043:1051	arg1	response					1063:1070	a sustained virologic response	1041:1070	a sustained virologic response	1041:1070	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11 patients who received treatment.
29342358	3	20	with	Replacement	523:533	arg1	trans-olefin					568:579	a trans-olefin	566:579	a trans-olefin	566:579	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	2	21	dep	effort	425:430	arg1	improve					435:441	improve	435:441	to improve on an original lead, inhibitor 1, which we described in a previous publication	432:520	This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication.
29342358	5	22	theme	HCV	922:924	arg1	patients					935:942	HCV infected patients	922:942	HCV infected patients	922:942	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	2	23	theme	chemistry	415:423	arg1	effort					425:430	a medicinal chemistry effort	403:430	a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication	403:520	This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication.
29342358	6	24	theme	phase	947:951	arg1	study					964:968	A phase 2 clinical study	945:968	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450	945:1030	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11 patients who received treatment.
29342358	0	25	theme	ABT-072	119:125	arg1	Discovery					106:114	Discovery	106:114	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.	0:182	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	4	26	from	Replacement	715:725	arg1	1					751:751	1	751:751	1	751:751	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	4	27	theme	dihydrouracil	734:746	arg1	Replacement					715:725	Replacement	715:725	Replacement of the dihydrouracil in 1 with an N-linked uracil	715:775	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	5	28	from	dosing	899:904	arg1	patients					935:942	HCV infected patients	922:942	HCV infected patients	922:942	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	0	29	theme	Biological	14:23	arg1	Characterization					25:40	Biological Characterization	14:40	Biological Characterization	14:40	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	1	30	theme	program	275:281	arg1	inhibitor					232:240	a non-nucleoside HCV NS5B polymerase inhibitor	195:240	a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	195:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	30	theme	program	275:281	arg1	part					265:268	part	265:268	part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	265:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	2	31	theme	previous	501:508	arg1	publication					510:520	a previous publication	499:520	a previous publication	499:520	This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication.
29342358	1	32	theme	infection	356:364	arg1	treatment					339:347	the treatment	335:347	the treatment of HCV infection	335:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	0	33	theme	Aryl	45:48	arg1	Inhibitors					57:66	Aryl Uracil Inhibitors	45:66	Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase	45:103	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	5	34	dep	phase	848:852	arg1	studies					865:871	clinical studies	856:871	phase 1 clinical studies	848:871	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	1	35	theme	non-nucleoside	197:210	arg1	inhibitor					232:240	a non-nucleoside HCV NS5B polymerase inhibitor	195:240	a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	195:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	35	theme	non-nucleoside	197:210	arg1	ABT-072					184:190	ABT-072	184:190	ABT-072	184:190	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	35	theme	non-nucleoside	197:210	arg1	part					265:268	part	265:268	part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	265:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	36	theme	HCV	212:214	arg1	inhibitor					232:240	a non-nucleoside HCV NS5B polymerase inhibitor	195:240	a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	195:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	36	theme	HCV	212:214	arg1	ABT-072					184:190	ABT-072	184:190	ABT-072	184:190	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	36	theme	HCV	212:214	arg1	part					265:268	part	265:268	part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	265:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	0	37	theme	Inhibitors	57:66	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis	0:8	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	0	37	theme	Inhibitors	57:66	arg1	Characterization					25:40	Biological Characterization	14:40	Biological Characterization	14:40	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	1	38	theme	new	295:297	arg1	DAAs					325:328	DAAs	325:328	DAAs	325:328	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	38	theme	new	295:297	arg1	antivirals					313:322	new direct-acting antivirals	295:322	new direct-acting antivirals (DAAs) for the treatment of HCV infection	295:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	6	39	theme	protease	1005:1012	arg1	inhibitor					1014:1022	the HCV protease inhibitor ABT-450	997:1030	the HCV protease inhibitor ABT-450	997:1030	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11 patients who received treatment.
29342358	3	40	theme	improved	593:600	arg1	permeability					611:622	improved compound permeability	593:622	improved compound permeability	593:622	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	3	41	theme	amide	542:546	arg1	linkage					548:554	the amide linkage	538:554	the amide linkage	538:554	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	5	42	theme	oral	894:897	arg1	dosing					899:904	once-daily oral dosing	883:904	once-daily oral dosing with ABT-072 in HCV infected patients	883:942	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	0	43	theme	Uracil	50:55	arg1	Inhibitors					57:66	Aryl Uracil Inhibitors	45:66	Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase	45:103	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	1	44	theme	direct-acting	299:311	arg1	DAAs					325:328	DAAs	325:328	DAAs	325:328	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	44	theme	direct-acting	299:311	arg1	antivirals					313:322	new direct-acting antivirals	295:322	new direct-acting antivirals (DAAs) for the treatment of HCV infection	295:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	0	45	theme	trans-Stilbene	130:143	arg1	Analog					145:150	a trans-Stilbene Analog	128:150	a trans-Stilbene Analog with Good Oral Bioavailability	128:181	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	0	45	theme	trans-Stilbene	130:143	arg1	ABT-072					119:125	ABT-072	119:125	ABT-072	119:125	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	3	46	theme	linkage	548:554	arg1	Replacement					523:533	Replacement	523:533	Replacement of the amide linkage in 1 with a trans-olefin	523:579	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	5	47	with	dosing	899:904	arg1	ABT-072					911:917	ABT-072	911:917	ABT-072	911:917	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	4	48	with	Replacement	715:725	arg1	uracil					770:775	an N-linked uracil	758:775	an N-linked uracil	758:775	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	0	49	theme	Good	157:160	arg1	Bioavailability					167:181	Good Oral Bioavailability	157:181	Good Oral Bioavailability	157:181	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	3	50	from	Replacement	523:533	arg1	1					559:559	1	559:559	1	559:559	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	1	51	theme	NS5B	216:219	arg1	inhibitor					232:240	a non-nucleoside HCV NS5B polymerase inhibitor	195:240	a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	195:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	51	theme	NS5B	216:219	arg1	ABT-072					184:190	ABT-072	184:190	ABT-072	184:190	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	51	theme	NS5B	216:219	arg1	part					265:268	part	265:268	part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	265:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	4	52	theme	N-linked	761:768	arg1	uracil					770:775	an N-linked uracil	758:775	an N-linked uracil	758:775	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	5	53	from	phase	848:852	arg1	Results					835:841	Results	835:841	Results from phase 1 clinical studies	835:871	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	1	54	theme	polymerase	221:230	arg1	inhibitor					232:240	a non-nucleoside HCV NS5B polymerase inhibitor	195:240	a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	195:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	54	theme	polymerase	221:230	arg1	ABT-072					184:190	ABT-072	184:190	ABT-072	184:190	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	1	54	theme	polymerase	221:230	arg1	part					265:268	part	265:268	part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection	265:364	ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of a program to identify new direct-acting antivirals (DAAs) for the treatment of HCV infection.
29342358	0	55	theme	Hepatitis	71:79	arg1	Virus					83:87	Hepatitis C Virus	71:87	Hepatitis C Virus NS5B Polymerase	71:103	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	4	56	link	N-linked	761:768	arg1	uracil					770:775	an N-linked uracil	758:775	an N-linked uracil	758:775	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	4	57	theme	better	786:791	arg1	potency					793:799	better potency	786:799	better potency	786:799	Replacement of the dihydrouracil in 1 with an N-linked uracil provided better potency in the genotype 1 replicon assay.
29342358	2	58	theme	medicinal	405:413	arg1	chemistry					415:423	a medicinal chemistry	403:423	a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication	403:520	This compound was identified during a medicinal chemistry effort to improve on an original lead, inhibitor 1, which we described in a previous publication.
29342358	5	59	theme	clinical	856:863	arg1	studies					865:871	clinical studies	856:871	phase 1 clinical studies	848:871	Results from phase 1 clinical studies supported once-daily oral dosing with ABT-072 in HCV infected patients.
29342358	3	60	theme	pharmacokinetic	664:678	arg1	properties					680:689	much better pharmacokinetic properties	652:689	much better pharmacokinetic properties	652:689	Replacement of the amide linkage in 1 with a trans-olefin resulted in improved compound permeability and solubility and provided much better pharmacokinetic properties in preclinical species.
29342358	0	61	dep	Synthesis	0:8	arg1	Discovery					106:114	Discovery	106:114	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.	0:182	Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good Oral Bioavailability.
29342358	6	62	theme	HCV	1001:1003	arg1	inhibitor					1014:1022	the HCV protease inhibitor ABT-450	997:1030	the HCV protease inhibitor ABT-450	997:1030	A phase 2 clinical study that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11 patients who received treatment.
30444296	2	0	from	India	438:442	arg1	treatment					387:395	a crucial therapeutic treatment	365:395	a crucial therapeutic treatment during the influenza epidemic of 1919 in India	365:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	2	0	from	India	438:442	arg1	A. paniculata					339:351	A. paniculata	339:351	A. paniculata	339:351	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	6	1	theme	transcriptome	1152:1164	arg1	data					1166:1169	transcriptome data	1152:1169	transcriptome data from seedlings elicited with methyl jasmonate	1152:1215	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	3	2	theme	anti-inflammatory	712:728	arg1	medicines					730:738	natural anti-inflammatory medicines	704:738	natural anti-inflammatory medicines	704:738	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	6	3	theme	UDP-dependent	1385:1397	arg1	glycosyltransferases					1399:1418	UDP-dependent glycosyltransferases	1385:1418	UDP-dependent glycosyltransferases	1385:1418	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	2	4	theme	crucial	367:373	arg1	treatment					387:395	a crucial therapeutic treatment	365:395	a crucial therapeutic treatment during the influenza epidemic of 1919 in India	365:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	2	4	theme	crucial	367:373	arg1	A. paniculata					339:351	A. paniculata	339:351	A. paniculata	339:351	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	7	5	theme	diterpene	1639:1647	arg1	scaffolds					1649:1657	diversified labdane-related diterpene scaffolds	1611:1657	diversified labdane-related diterpene scaffolds	1611:1657	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	3	6	theme	anti-inflammatory	560:576	arg1	lactones					590:597	the anti-inflammatory diterpenoid lactones	556:597	the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide	556:636	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	6	theme	anti-inflammatory	560:576	arg1	neoandrographolide					619:636	neoandrographolide	619:636	neoandrographolide	619:636	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	6	theme	anti-inflammatory	560:576	arg1	andrographolide					599:613	andrographolide	599:613	andrographolide	599:613	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	7	7	theme	diversified	1611:1621	arg1	scaffolds					1649:1657	diversified labdane-related diterpene scaffolds	1611:1657	diversified labdane-related diterpene scaffolds	1611:1657	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	4	8	theme	genome	901:906	arg1	sequence					908:915	a chromosome-scale A. paniculata genome sequence	868:915	a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data	868:1019	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	7	9	theme	synthases	1567:1575	arg1	pairs					1532:1536	pairs	1532:1536	pairs of class-I and -II diterpene synthases	1532:1575	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	7	10	theme	-II	1553:1555	arg1	synthases					1567:1575	class-I and -II diterpene synthases	1541:1575	synthases	1567:1575	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	6	11	theme	P450	1322:1325	arg1	monooxygenases					1327:1340	cytochrome P450 monooxygenases	1311:1340	cytochrome P450 monooxygenases	1311:1340	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	2	12	from	treatment	387:395	arg1	India					438:442	India	438:442	India	438:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	7	13	theme	class-I	1541:1547	arg1	synthases					1567:1575	class-I and -II diterpene synthases	1541:1575	synthases	1567:1575	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	3	14	theme	neurodegenerative	770:786	arg1	disorders					788:796	neurodegenerative disorders	770:796	neurodegenerative disorders	770:796	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	0	15	theme	diterpenoid	114:124	arg1	neoandrographolide					126:143	the bioactive diterpenoid neoandrographolide	100:143	the bioactive diterpenoid neoandrographolide	100:143	The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.
30444296	3	16	theme	lactones	590:597	arg1	generation					690:699	the next generation	681:699	the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases	681:849	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	16	theme	lactones	590:597	arg1	quantities					542:551	large quantities	536:551	large quantities	536:551	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	9	17	theme	genomic	1886:1892	arg1	data					1913:1916	the combined genomic and transcriptomic data	1873:1916	the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1873:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	7	18	theme	pairs	1532:1536	arg1	characterization					1512:1527	functional characterization	1501:1527	functional characterization of pairs of class-I and -II diterpene synthases	1501:1575	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	3	19	theme	inflammatory	824:835	arg1	diseases					842:849	inflammatory skin diseases	824:849	inflammatory skin diseases	824:849	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	6	20	theme	lactone	1456:1462	arg1	biosynthesis					1464:1475	diterpenoid lactone biosynthesis	1444:1475	diterpenoid lactone biosynthesis	1444:1475	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	9	21	theme	transcriptomic	1898:1911	arg1	data					1913:1916	the combined genomic and transcriptomic data	1873:1916	the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1873:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	1	22	theme	Andrographis	146:157	arg1	plant					192:196	a herbaceous dicot plant	173:196	a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries	173:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	1	22	theme	Andrographis	146:157	arg1	paniculata					159:168	Andrographis paniculata	146:168	Andrographis paniculata	146:168	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	3	23	dep	lactones	590:597	arg1	lactones					590:597	the anti-inflammatory diterpenoid lactones	556:597	the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide	556:636	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	23	dep	lactones	590:597	arg1	neoandrographolide					619:636	neoandrographolide	619:636	neoandrographolide	619:636	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	23	dep	lactones	590:597	arg1	andrographolide					599:613	andrographolide	599:613	andrographolide	599:613	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	2	24	theme	disease	495:501	arg1	treatment					471:479	the treatment	467:479	the treatment of infectious disease in China	467:510	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	1	25	theme	herbaceous	175:184	arg1	plant					192:196	a herbaceous dicot plant	173:196	a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries	173:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	1	25	theme	herbaceous	175:184	arg1	paniculata					159:168	Andrographis paniculata	146:168	Andrographis paniculata	146:168	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	4	26	theme	high-confidence	993:1007	arg1	data					1016:1019	high-confidence (Hi-C) data	993:1019	high-confidence (Hi-C) data	993:1019	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	6	27	theme	genes	1273:1277	arg1	identification					1255:1268	the identification	1251:1268	the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis	1251:1475	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	9	28	theme	production	1966:1975	arg1	investigation					1945:1957	the investigation	1941:1957	the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1941:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	5	29	theme	Gene	1022:1025	arg1	annotation					1027:1036	Gene annotation	1022:1036	Gene annotation	1022:1036	Gene annotation predicted 25 428 protein-coding genes.
30444296	6	30	theme	diterpenoid	1126:1136	arg1	biosynthesis					1138:1149	diterpenoid biosynthesis	1126:1149	diterpenoid biosynthesis	1126:1149	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	2	31	from	treatment	471:479	arg1	China					506:510	China	506:510	China	506:510	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	2	32	used	used	357:360	arg2	A. paniculata					339:351	A. paniculata	339:351	A. paniculata	339:351	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	2	32	used	used	357:360	arg2	treatment					387:395	a crucial therapeutic treatment	365:395	a crucial therapeutic treatment during the influenza epidemic of 1919 in India	365:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	9	33	theme	diterpenoid	1994:2004	arg1	constituents					2014:2025	the bioactive diterpenoid lactone constituents	1980:2025	the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1980:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	8	34	theme	O-linked	1712:1719	arg1	glucosylation					1721:1733	O-linked glucosylation	1712:1733	O-linked glucosylation of andrograpanin	1712:1750	In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified.
30444296	1	35	theme	other	306:310	arg1	countries					328:336	other Southeast Asian countries	306:336	other Southeast Asian countries	306:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	9	36	theme	constituents	2014:2025	arg1	production					1966:1975	the production	1962:1975	the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1962:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	0	37	theme	medicinal	18:26	arg1	paniculata					47:56	the medicinal plant Andrographis paniculata	14:56	the medicinal plant Andrographis paniculata	14:56	The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.
30444296	1	38	theme	Asian	322:326	arg1	countries					328:336	other Southeast Asian countries	306:336	other Southeast Asian countries	306:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	4	39	theme	chromosome-scale	870:885	arg1	sequence					908:915	a chromosome-scale A. paniculata genome sequence	868:915	a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data	868:1019	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	6	40	from	seedlings	1176:1184	arg1	data					1166:1169	transcriptome data	1152:1169	transcriptome data from seedlings elicited with methyl jasmonate	1152:1215	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	0	41	theme	Andrographis	34:45	arg1	paniculata					47:56	the medicinal plant Andrographis paniculata	14:56	the medicinal plant Andrographis paniculata	14:56	The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.
30444296	9	42	theme	medicinal	2044:2052	arg1	herb					2054:2057	the important medicinal herb	2030:2057	the important medicinal herb A. paniculata	2030:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	3	43	theme	natural	704:710	arg1	medicines					730:738	natural anti-inflammatory medicines	704:738	natural anti-inflammatory medicines	704:738	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	7	44	contain	carried	1489:1495	arg2	characterization					1512:1527	functional characterization	1501:1527	functional characterization of pairs of class-I and -II diterpene synthases	1501:1575	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	7	44	contain	carried	1489:1495	arg1	We					1478:1479	We	1478:1479	We	1478:1479	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	9	45	theme	A. paniculata	2059:2071	arg1	constituents					2014:2025	the bioactive diterpenoid lactone constituents	1980:2025	the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1980:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	8	46	theme	active	1772:1777	arg1	neoandrographolide					1787:1804	the major active product neoandrographolide	1762:1804	the major active product neoandrographolide	1762:1804	In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified.
30444296	5	47	theme	protein-coding	1055:1068	arg1	genes					1070:1074	25 428 protein-coding genes	1048:1074	25 428 protein-coding genes	1048:1074	Gene annotation predicted 25 428 protein-coding genes.
30444296	3	48	theme	lung	744:747	arg1	diseases					749:756	lung diseases	744:756	lung diseases	744:756	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	2	49	theme	therapeutic	375:385	arg1	treatment					387:395	a crucial therapeutic treatment	365:395	a crucial therapeutic treatment during the influenza epidemic of 1919 in India	365:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	2	49	theme	therapeutic	375:385	arg1	A. paniculata					339:351	A. paniculata	339:351	A. paniculata	339:351	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	7	50	theme	labdane-related	1623:1637	arg1	scaffolds					1649:1657	diversified labdane-related diterpene scaffolds	1611:1657	diversified labdane-related diterpene scaffolds	1611:1657	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	4	51	theme	269 Mb	920:925	arg1	sequence					908:915	a chromosome-scale A. paniculata genome sequence	868:915	a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data	868:1019	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	3	52	theme	medicines	730:738	arg1	generation					690:699	the next generation	681:699	the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases	681:849	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	52	theme	medicines	730:738	arg1	quantities					542:551	large quantities	536:551	large quantities	536:551	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	6	53	theme	2-oxoglutarate-dependent	1343:1366	arg1	dioxygenases					1368:1379	2-oxoglutarate-dependent dioxygenases	1343:1379	2-oxoglutarate-dependent dioxygenases	1343:1379	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	1	54	theme	dicot	186:190	arg1	plant					192:196	a herbaceous dicot plant	173:196	a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries	173:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	1	54	theme	dicot	186:190	arg1	paniculata					159:168	Andrographis paniculata	146:168	Andrographis paniculata	146:168	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	4	55	theme	A. paniculata	887:899	arg1	sequence					908:915	a chromosome-scale A. paniculata genome sequence	868:915	a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data	868:1019	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	8	56	link	O-linked	1712:1719	arg1	glucosylation					1721:1733	O-linked glucosylation	1712:1733	O-linked glucosylation of andrograpanin	1712:1750	In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified.
30444296	2	57	used	used	458:461	arg2	A. paniculata					339:351	A. paniculata	339:351	A. paniculata	339:351	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	2	57	used	used	458:461	arg2	treatment					387:395	a crucial therapeutic treatment	365:395	a crucial therapeutic treatment during the influenza epidemic of 1919 in India	365:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	7	58	theme	diterpene	1557:1565	arg1	synthases					1567:1575	class-I and -II diterpene synthases	1541:1575	synthases	1567:1575	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	3	59	theme	autoimmune	799:808	arg1	disorders					810:818	autoimmune disorders	799:818	autoimmune disorders	799:818	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	0	60	theme	neoandrographolide	126:143	arg1	biosynthesis					84:95	the biosynthesis	80:95	the biosynthesis of the bioactive diterpenoid neoandrographolide	80:143	The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.
30444296	3	61	theme	diterpenoid	578:588	arg1	lactones					590:597	the anti-inflammatory diterpenoid lactones	556:597	the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide	556:636	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	61	theme	diterpenoid	578:588	arg1	neoandrographolide					619:636	neoandrographolide	619:636	neoandrographolide	619:636	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	61	theme	diterpenoid	578:588	arg1	andrographolide					599:613	andrographolide	599:613	andrographolide	599:613	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	9	62	theme	combined	1877:1884	arg1	data					1913:1916	the combined genomic and transcriptomic data	1873:1916	the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1873:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	2	63	from	disease	495:501	arg1	China					506:510	China	506:510	China	506:510	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	1	64	from	distribution	273:284	arg1	countries					328:336	other Southeast Asian countries	306:336	other Southeast Asian countries	306:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	1	64	from	distribution	273:284	arg1	India					296:300	India	296:300	India	296:300	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	1	64	from	distribution	273:284	arg1	China					289:293	China	289:293	China	289:293	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	1	65	theme	anti-inflammatory	218:234	arg1	properties					251:260	its anti-inflammatory and anti-viral properties	214:260	its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries	214:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	4	66	theme	long	978:981	arg1	PacBio					971:976	PacBio long reads	971:987	PacBio long reads	971:987	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	2	67	from	China	506:510	arg1	treatment					471:479	the treatment	467:479	the treatment of infectious disease in China	467:510	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	3	68	theme	skin	837:840	arg1	diseases					842:849	inflammatory skin diseases	824:849	inflammatory skin diseases	824:849	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	6	69	theme	diterpenoid	1444:1454	arg1	biosynthesis					1464:1475	diterpenoid lactone biosynthesis	1444:1475	diterpenoid lactone biosynthesis	1444:1475	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	9	70	theme	data	1913:1916	arg1	utility					1862:1868	the utility	1858:1868	the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1858:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	6	71	theme	diterpenoid	1288:1298	arg1	synthases					1300:1308	diterpenoid synthases	1288:1308	diterpenoid synthases	1288:1308	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	4	72	theme	short	958:962	arg1	Illumina					949:956	Illumina short reads	949:968	Illumina short reads	949:968	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	7	73	theme	functional	1501:1510	arg1	characterization					1512:1527	functional characterization	1501:1527	functional characterization of pairs of class-I and -II diterpene synthases	1501:1575	We further carried out functional characterization of pairs of class-I and -II diterpene synthases, revealing the ability to produce diversified labdane-related diterpene scaffolds.
30444296	3	74	theme	analogs	649:655	arg1	generation					690:699	the next generation	681:699	the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases	681:849	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	74	theme	analogs	649:655	arg1	quantities					542:551	large quantities	536:551	large quantities	536:551	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	1	75	theme	anti-viral	240:249	arg1	properties					251:260	its anti-inflammatory and anti-viral properties	214:260	its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries	214:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	4	76	dep	Illumina	949:956	arg1	reads					964:968	reads	964:968	reads	964:968	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	2	77	theme	infectious	484:493	arg1	disease					495:501	infectious disease	484:501	infectious disease in China	484:510	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	8	78	theme	able	1695:1698	arg1	glycosyltransferase					1675:1693	a glycosyltransferase	1673:1693	a glycosyltransferase	1673:1693	In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified.
30444296	0	79	theme	bioactive	104:112	arg1	neoandrographolide					126:143	the bioactive diterpenoid neoandrographolide	100:143	the bioactive diterpenoid neoandrographolide	100:143	The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.
30444296	6	80	theme	biosynthesis	1138:1149	arg1	genetic					1102:1108	genetic	1102:1108	genetic	1102:1108	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	4	81	dep	PacBio	971:976	arg1	reads					983:987	reads	983:987	reads	983:987	Here, we report a chromosome-scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and high-confidence (Hi-C) data.
30444296	9	82	theme	bioactive	1984:1992	arg1	constituents					2014:2025	the bioactive diterpenoid lactone constituents	1980:2025	the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1980:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	6	83	theme	cytochrome	1311:1320	arg1	monooxygenases					1327:1340	cytochrome P450 monooxygenases	1311:1340	cytochrome P450 monooxygenases	1311:1340	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	9	84	theme	lactone	2006:2012	arg1	constituents					2014:2025	the bioactive diterpenoid lactone constituents	1980:2025	the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata	1980:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	8	85	theme	andrograpanin	1738:1750	arg1	glucosylation					1721:1733	O-linked glucosylation	1712:1733	O-linked glucosylation of andrograpanin	1712:1750	In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified.
30444296	0	86	theme	plant	28:32	arg1	paniculata					47:56	the medicinal plant Andrographis paniculata	14:56	the medicinal plant Andrographis paniculata	14:56	The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.
30444296	1	87	theme	Southeast	312:320	arg1	countries					328:336	other Southeast Asian countries	306:336	other Southeast Asian countries	306:336	Andrographis paniculata is a herbaceous dicot plant widely used for its anti-inflammatory and anti-viral properties across its distribution in China, India and other Southeast Asian countries.
30444296	2	88	theme	1919	430:433	arg1	treatment					387:395	a crucial therapeutic treatment	365:395	a crucial therapeutic treatment during the influenza epidemic of 1919 in India	365:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	2	88	theme	1919	430:433	arg1	A. paniculata					339:351	A. paniculata	339:351	A. paniculata	339:351	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	0	89	theme	paniculata	47:56	arg1	genome					4:9	The genome	0:9	The genome of the medicinal plant Andrographis paniculata	0:56	The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide.
30444296	6	90	theme	methyl	1200:1205	arg1	jasmonate					1207:1215	methyl jasmonate	1200:1215	methyl jasmonate	1200:1215	In order to decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate were also obtained, which enabled the identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2-oxoglutarate-dependent dioxygenases and UDP-dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis.
30444296	9	91	theme	important	2034:2042	arg1	herb					2054:2057	the important medicinal herb	2030:2057	the important medicinal herb A. paniculata	2030:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	8	92	theme	major	1766:1770	arg1	neoandrographolide					1787:1804	the major active product neoandrographolide	1762:1804	the major active product neoandrographolide	1762:1804	In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified.
30444296	9	93	theme	herb	2054:2057	arg1	A. paniculata					2059:2071	the important medicinal herb A. paniculata	2030:2071	the important medicinal herb A. paniculata	2030:2071	Thus, our results demonstrate the utility of the combined genomic and transcriptomic data set generated here for the investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
30444296	8	94	theme	product	1779:1785	arg1	neoandrographolide					1787:1804	the major active product neoandrographolide	1762:1804	the major active product neoandrographolide	1762:1804	In addition, a glycosyltransferase able to catalyze O-linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was also identified.
30444296	3	95	theme	next	685:688	arg1	generation					690:699	the next generation	681:699	the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases	681:849	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	95	theme	next	685:688	arg1	quantities					542:551	large quantities	536:551	large quantities	536:551	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	2	96	from	1919	430:433	arg1	India					438:442	India	438:442	India	438:442	A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India, and is still used for the treatment of infectious disease in China.
30444296	3	97	theme	large	536:540	arg1	generation					690:699	the next generation	681:699	the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases	681:849	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
30444296	3	97	theme	large	536:540	arg1	quantities					542:551	large quantities	536:551	large quantities	536:551	A. paniculata produces large quantities of the anti-inflammatory diterpenoid lactones andrographolide and neoandrographolide, and their analogs, which are touted to be the next generation of natural anti-inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases.
29859938	0	0	theme	IL-8	101:104	arg1	release					106:112	IL-8 release	101:112	IL-8 release	101:112	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	9	1	theme	CD63	1425:1428	arg1	expression					1430:1439	CD63 expression	1425:1439	CD63 expression	1425:1439	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	8	2	theme	BLT1	1373:1376	arg1	siRNA					1378:1382	BLT1 siRNA	1373:1382	BLT1 siRNA	1373:1382	Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA.
29859938	9	3	theme	TvSP-induced	1385:1396	arg1	migration					1398:1406	TvSP-induced migration	1385:1406	TvSP-induced migration	1385:1406	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	6	4	theme	vaginalis-secreted	1091:1108	arg1	leukotrienes					1110:1121	T. vaginalis-secreted leukotrienes	1088:1121	T. vaginalis-secreted leukotrienes	1088:1121	This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes.
29859938	8	5	theme	OGT	1301:1303	arg1	expression					1305:1314	OGT expression	1301:1314	OGT expression	1301:1314	Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA.
29859938	1	6	theme	Trichomonas	181:191	arg1	parasite					239:246	a sexually-transmitted protozoan parasite	206:246	a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis	206:283	Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis.
29859938	1	6	theme	Trichomonas	181:191	arg1	vaginalis					193:201	Trichomonas vaginalis	181:201	Trichomonas vaginalis	181:201	Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis.
29859938	6	7	theme	T.	1088:1089	arg1	leukotrienes					1110:1121	T. vaginalis-secreted leukotrienes	1088:1121	T. vaginalis-secreted leukotrienes	1088:1121	This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes.
29859938	7	8	theme	mast	1199:1202	arg1	cells					1204:1208	mast cells	1199:1208	mast cells	1199:1208	Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1).
29859938	4	9	theme	vaginalis-derived	836:852	arg1	TvSP					874:877	TvSP	874:877	TvSP	874:877	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	4	9	theme	vaginalis-derived	836:852	arg1	products					864:871	vaginalis-derived secretory products	836:871	T. vaginalis-derived secretory products (TvSP)	833:878	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	3	10	theme	critical	636:643	arg1	modification					570:581	a post-translational modification	549:581	a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)	549:743	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	10	theme	critical	636:643	arg1	regulator					645:653	a critical regulator	634:653	a critical regulator	634:653	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	2	11	with	infection	370:378	arg1	parasites					385:393	parasites	385:393	parasites	385:393	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	8	12	with	transfection	1355:1366	arg1	siRNA					1378:1382	BLT1 siRNA	1373:1382	BLT1 siRNA	1373:1382	Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA.
29859938	7	13	theme	cells	1204:1208	arg1	migration					1186:1194	migration	1186:1194	migration of mast cells	1186:1208	Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1).
29859938	9	14	with	pretreatment	1491:1502	arg1	siRNA					1539:1543	OGT siRNA	1535:1543	OGT siRNA	1535:1543	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	9	14	with	pretreatment	1491:1502	arg1	inhibitor					1513:1521	OGT inhibitor ST045849	1509:1530	OGT inhibitor ST045849	1509:1530	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	9	15	theme	IL-8	1445:1448	arg1	release					1450:1456	IL-8 release	1445:1456	IL-8 release	1445:1456	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	10	16	theme	cell	1627:1630	arg1	activation					1632:1641	mast cell activation	1622:1641	mast cell activation during trichomoniasis	1622:1663	These results suggested that BLT1-mediated OGlcNAcylation was important for mast cell activation during trichomoniasis.
29859938	0	17	theme	mast	123:126	arg1	cell					128:131	human mast cell	117:131	human mast cell induced by Trichomonas vaginalis-secreted LTB4	117:178	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	5	18	theme	cells	1005:1009	arg1	migration					987:995	migration	987:995	migration of mast cells	987:1009	Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells.
29859938	5	19	theme	5-lipooxygenase	945:959	arg1	AA861					971:975	the 5-lipooxygenase inhibitor AA861	941:975	the 5-lipooxygenase inhibitor AA861	941:975	Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells.
29859938	5	20	theme	inhibitor	961:969	arg1	AA861					971:975	the 5-lipooxygenase inhibitor AA861	941:975	the 5-lipooxygenase inhibitor AA861	941:975	Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells.
29859938	0	21	theme	human	117:121	arg1	cell					128:131	human mast cell	117:131	human mast cell induced by Trichomonas vaginalis-secreted LTB4	117:178	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	5	22	theme	mast	1000:1003	arg1	cells					1005:1009	mast cells	1000:1009	mast cells	1000:1009	Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells.
29859938	10	23	theme	BLT1-mediated	1575:1587	arg1	OGlcNAcylation					1589:1602	BLT1-mediated OGlcNAcylation	1575:1602	BLT1-mediated OGlcNAcylation	1575:1602	These results suggested that BLT1-mediated OGlcNAcylation was important for mast cell activation during trichomoniasis.
29859938	4	24	theme	secretory	854:862	arg1	TvSP					874:877	TvSP	874:877	TvSP	874:877	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	4	24	theme	secretory	854:862	arg1	products					864:871	vaginalis-derived secretory products	836:871	T. vaginalis-derived secretory products (TvSP)	833:878	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	2	25	theme	cell	451:454	arg1	activation					456:465	mast cell activation	446:465	mast cell activation	446:465	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	5	26	theme	Modified	881:888	arg1	TvSP					890:893	Modified TvSP	881:893	Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861	881:975	Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells.
29859938	9	27	theme	ROS	1409:1411	arg1	generation					1413:1422	ROS generation	1409:1422	ROS generation	1409:1422	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	8	28	dep	induced	1265:1271	arg1	prevented					1342:1350	prevented	1342:1350	was prevented by transfection with BLT1 siRNA	1338:1382	Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA.
29859938	2	29	theme	mast	446:449	arg1	activation					456:465	mast cell activation	446:465	mast cell activation	446:465	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	0	30	theme	BLT1-mediated	0:12	arg1	O-GlcNAcylation					14:28	BLT1-mediated O-GlcNAcylation	0:28	BLT1-mediated O-GlcNAcylation	0:28	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	3	31	link	O-linked	506:513	arg1	modification					570:581	a post-translational modification	549:581	a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)	549:743	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	31	link	O-linked	506:513	arg1	O-GlcNAc					536:543	O-GlcNAc	536:543	O-GlcNAc	536:543	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	31	link	O-linked	506:513	arg1	N-acetylglucosamine					515:533	O-linked N-acetylglucosamine	506:533	O-linked N-acetylglucosamine (O-GlcNAc)	506:544	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	2	32	from	mechanisms	432:441	arg1	activation					456:465	mast cell activation	446:465	mast cell activation	446:465	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	2	32	from	mechanisms	432:441	arg1	infection					484:492	T. vaginalis infection	471:492	T. vaginalis infection	471:492	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	3	33	dep	serine	586:591	arg1	residues					607:614	residues	607:614	residues	607:614	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	1	34	theme	sexually-transmitted	208:227	arg1	parasite					239:246	a sexually-transmitted protozoan parasite	206:246	a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis	206:283	Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis.
29859938	1	34	theme	sexually-transmitted	208:227	arg1	vaginalis					193:201	Trichomonas vaginalis	181:201	Trichomonas vaginalis	181:201	Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis.
29859938	8	35	theme	protein	1273:1279	arg1	O-GlcNAcylation					1281:1295	protein O-GlcNAcylation	1273:1295	protein O-GlcNAcylation	1273:1295	Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA.
29859938	1	36	theme	protozoan	229:237	arg1	parasite					239:246	a sexually-transmitted protozoan parasite	206:246	a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis	206:283	Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis.
29859938	1	36	theme	protozoan	229:237	arg1	vaginalis					193:201	Trichomonas vaginalis	181:201	Trichomonas vaginalis	181:201	Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis.
29859938	4	37	theme	cell	806:809	arg1	activation					811:820	mast cell activation	801:820	mast cell activation induced by T. vaginalis-derived secretory products (TvSP)	801:878	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	7	38	theme	BLT1	1160:1163	arg1	siRNA					1165:1169	BLT1 siRNA	1160:1169	BLT1 siRNA	1160:1169	Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1).
29859938	0	39	theme	cell	128:131	arg1	migration					61:69	NOX2-dependent migration	46:69	NOX2-dependent migration	46:69	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	0	39	theme	cell	128:131	arg1	degranulation					83:95	exocytotic degranulation	72:95	exocytotic degranulation	72:95	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	0	39	theme	cell	128:131	arg1	release					106:112	IL-8 release	101:112	IL-8 release	101:112	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	2	40	theme	tissue	343:348	arg1	inflammation					350:361	tissue inflammation	343:361	tissue inflammation	343:361	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	2	41	theme	vaginalis	474:482	arg1	infection					484:492	T. vaginalis infection	471:492	T. vaginalis infection	471:492	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	0	42	theme	NOX2-dependent	46:59	arg1	migration					61:69	NOX2-dependent migration	46:69	NOX2-dependent migration	46:69	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	0	43	theme	Trichomonas	144:154	arg1	LTB4					175:178	Trichomonas vaginalis-secreted LTB4	144:178	Trichomonas vaginalis-secreted LTB4	144:178	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	2	44	theme	T.	471:472	arg1	infection					484:492	T. vaginalis infection	471:492	T. vaginalis infection	471:492	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	6	45	theme	cell	1044:1047	arg1	migration					1049:1057	mast cell migration	1039:1057	mast cell migration	1039:1057	This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes.
29859938	9	46	theme	OGT	1509:1511	arg1	inhibitor					1513:1521	OGT inhibitor ST045849	1509:1530	OGT inhibitor ST045849	1509:1530	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	10	47	theme	mast	1622:1625	arg1	activation					1632:1641	mast cell activation	1622:1641	mast cell activation during trichomoniasis	1622:1663	These results suggested that BLT1-mediated OGlcNAcylation was important for mast cell activation during trichomoniasis.
29859938	6	48	theme	mast	1039:1042	arg1	migration					1049:1057	mast cell migration	1039:1057	mast cell migration	1039:1057	This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes.
29859938	3	49	theme	intracellular	658:670	arg1	signaling					672:680	intracellular signaling	658:680	intracellular signaling	658:680	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	7	50	theme	BLT1	1134:1137	arg1	U75302					1150:1155	the BLT1 antagonist U75302	1130:1155	the BLT1 antagonist U75302	1130:1155	Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1).
29859938	3	51	theme	post-translational	551:568	arg1	modification					570:581	a post-translational modification	549:581	a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)	549:743	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	51	theme	post-translational	551:568	arg1	regulator					645:653	a critical regulator	634:653	a critical regulator	634:653	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	51	theme	post-translational	551:568	arg1	N-acetylglucosamine					515:533	O-linked N-acetylglucosamine	506:533	O-linked N-acetylglucosamine (O-GlcNAc)	506:544	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	7	52	theme	LTB4	1225:1228	arg1	receptor					1230:1237	LTB4 receptor	1225:1237	LTB4 receptor (BLT1)	1225:1244	Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1).
29859938	7	52	theme	LTB4	1225:1228	arg1	BLT1					1240:1243	BLT1	1240:1243	BLT1	1240:1243	Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1).
29859938	0	53	theme	vaginalis-secreted	156:173	arg1	LTB4					175:178	Trichomonas vaginalis-secreted LTB4	144:178	Trichomonas vaginalis-secreted LTB4	144:178	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	3	54	theme	signaling	672:680	arg1	modification					570:581	a post-translational modification	549:581	a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)	549:743	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	54	theme	signaling	672:680	arg1	regulator					645:653	a critical regulator	634:653	a critical regulator	634:653	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	55	theme	serine	586:591	arg1	modification					570:581	a post-translational modification	549:581	a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)	549:743	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	55	theme	serine	586:591	arg1	regulator					645:653	a critical regulator	634:653	a critical regulator	634:653	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	55	theme	serine	586:591	arg1	N-acetylglucosamine					515:533	O-linked N-acetylglucosamine	506:533	O-linked N-acetylglucosamine (O-GlcNAc)	506:544	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	4	56	dep	T.	833:834	arg1	TvSP					874:877	TvSP	874:877	TvSP	874:877	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	4	56	dep	T.	833:834	arg1	products					864:871	vaginalis-derived secretory products	836:871	T. vaginalis-derived secretory products (TvSP)	833:878	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	4	57	link	vaginalis-derived	836:852	arg1	TvSP					874:877	TvSP	874:877	TvSP	874:877	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	4	57	link	vaginalis-derived	836:852	arg1	products					864:871	vaginalis-derived secretory products	836:871	T. vaginalis-derived secretory products (TvSP)	833:878	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	9	58	theme	OGT	1535:1537	arg1	siRNA					1539:1543	OGT siRNA	1535:1543	OGT siRNA	1535:1543	TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA.
29859938	7	59	theme	antagonist	1139:1148	arg1	U75302					1150:1155	the BLT1 antagonist U75302	1130:1155	the BLT1 antagonist U75302	1130:1155	Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1).
29859938	2	60	theme	cell	300:303	arg1	activation					305:314	mast cell activation	295:314	mast cell activation	295:314	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	3	61	theme	threonine	597:605	arg1	modification					570:581	a post-translational modification	549:581	a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)	549:743	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	61	theme	threonine	597:605	arg1	regulator					645:653	a critical regulator	634:653	a critical regulator	634:653	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	61	theme	threonine	597:605	arg1	N-acetylglucosamine					515:533	O-linked N-acetylglucosamine	506:533	O-linked N-acetylglucosamine (O-GlcNAc)	506:544	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	4	62	theme	mast	801:804	arg1	activation					811:820	mast cell activation	801:820	mast cell activation induced by T. vaginalis-derived secretory products (TvSP)	801:878	We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP).
29859938	2	63	theme	mast	295:298	arg1	activation					305:314	mast cell activation	295:314	mast cell activation	295:314	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	5	64	theme	live	910:913	arg1	trichomonads					915:926	live trichomonads	910:926	live trichomonads treated with the 5-lipooxygenase inhibitor AA861	910:975	Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells.
29859938	3	65	theme	O-linked	506:513	arg1	modification					570:581	a post-translational modification	549:581	a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)	549:743	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	65	theme	O-linked	506:513	arg1	O-GlcNAc					536:543	O-GlcNAc	536:543	O-GlcNAc	536:543	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	65	theme	O-linked	506:513	arg1	N-acetylglucosamine					515:533	O-linked N-acetylglucosamine	506:533	O-linked N-acetylglucosamine (O-GlcNAc)	506:544	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	0	66	theme	exocytotic	72:81	arg1	degranulation					83:95	exocytotic degranulation	72:95	exocytotic degranulation	72:95	BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4.
29859938	3	67	theme	O-GlcNAc	696:703	arg1	OGT					718:720	OGT	718:720	OGT	718:720	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	3	67	theme	O-GlcNAc	696:703	arg1	transferase					705:715	O-GlcNAc transferase	696:715	O-GlcNAc transferase (OGT)	696:721	O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA).
29859938	2	68	theme	signaling	422:430	arg1	mechanisms					432:441	the signaling mechanisms	418:441	the signaling mechanisms in mast cell activation and T. vaginalis infection	418:492	Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited.
29859938	6	69	theme	leukotrienes	1110:1121	arg1	stimulation					1073:1083	stimulation	1073:1083	stimulation of T. vaginalis-secreted leukotrienes	1073:1121	This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes.
29171040	7	0	from	IL-1β	1480:1484	arg1	cells					1493:1497	HCC cells	1489:1497	HCC cells	1489:1497	Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells through cyclooxygenase-2.
29171040	2	1	theme	cells	444:448	arg1	involvement					422:432	the involvement	418:432	the involvement of cancer cells under such conditions	418:470	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	2	1	theme	cells	444:448	arg1	interplay					380:388	the interplay	376:388	the interplay between the two factors	376:412	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	10	2	dep	CONCLUSION	1741:1750	arg1	revealed					1765:1772	revealed	1765:1772	revealed	1765:1772	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	10	2	dep	CONCLUSION	1741:1750	arg1	suggest					1995:2001	suggest	1995:2001	suggest a potential role of an anti-inflammatory strategy in HCC treatment	1995:2068	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	10	3	theme	hypoxic	1864:1870	arg1	microenvironment					1872:1887	a hypoxic microenvironment	1862:1887	a hypoxic microenvironment	1862:1887	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	4	4	theme	persistent	736:745	arg1	hypoxia					758:764	persistent and severe hypoxia	736:764	persistent and severe hypoxia	736:764	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	6	5	gly	glycosylation	1292:1304	arg1	proteins					1269:1276	proteins	1269:1276	proteins with O-linked glycosylation	1269:1304	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	3	6	theme	hypoxic	643:649	arg1	conditions					651:660	moderate hypoxic conditions	634:660	moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α)	634:727	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	5	7	theme	debris-induced	936:949	arg1	secretion					957:965	the necrotic debris-induced IL-1β secretion	923:965	the necrotic debris-induced IL-1β secretion	923:965	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	9	8	theme	HCC	1727:1729	arg1	patients					1731:1738	HCC patients	1727:1738	HCC patients	1727:1738	We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients.
29171040	5	9	theme	lipopolysaccharide-induced	1178:1203	arg1	inflammation					1205:1216	lipopolysaccharide-induced inflammation	1178:1216	lipopolysaccharide-induced inflammation	1178:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	5	10	theme	Toll-like	988:996	arg1	signaling					1124:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling	988:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	10	11	theme	signaling	1790:1798	arg1	loop					1800:1803	an HIF-1α/IL-1β signaling loop	1774:1803	an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages	1774:1857	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	3	12	theme	increased	669:677	arg1	stability					679:687	increased stability	669:687	increased stability of hypoxia inducible factor 1α (HIF-1α)	669:727	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	6	13	with	proteins	1269:1276	arg1	glycosylation					1292:1304	O-linked glycosylation	1283:1304	O-linked glycosylation	1283:1304	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	5	14	theme	identical	1156:1164	arg1	fashion					1167:1173	a similar, but not identical, fashion	1137:1173	a similar, but not identical, fashion	1137:1173	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	3	15	theme	due	662:664	arg1	conditions					651:660	moderate hypoxic conditions	634:660	moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α)	634:727	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	9	16	theme	HCC	1656:1658	arg1	metastasis					1660:1669	HCC metastasis	1656:1669	HCC metastasis	1656:1669	We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients.
29171040	10	17	theme	anti-inflammatory	2026:2042	arg1	strategy					2044:2051	an anti-inflammatory strategy	2023:2051	an anti-inflammatory strategy	2023:2051	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	6	18	theme	IL-1β	1356:1360	arg1	secretion					1362:1370	the necrotic debris-induced IL-1β secretion	1328:1370	the necrotic debris-induced IL-1β secretion	1328:1370	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	8	19	theme	epithelial-mesenchymal	1529:1550	arg1	transition					1552:1561	The epithelial-mesenchymal transition	1525:1561	The epithelial-mesenchymal transition of HCC cells	1525:1574	The epithelial-mesenchymal transition of HCC cells was enhanced by overexpression of HIF-1α.
29171040	3	20	theme	inducible	700:708	arg1	factor					710:715	hypoxia inducible factor 1α	692:718	hypoxia inducible factor 1α (HIF-1α)	692:727	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	3	20	theme	inducible	700:708	arg1	HIF-1α					721:726	HIF-1α	721:726	HIF-1α	721:726	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	5	21	theme	4/TIR	1007:1011	arg1	signaling					1124:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling	988:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	6	22	theme	necrotic	1332:1339	arg1	secretion					1362:1370	the necrotic debris-induced IL-1β secretion	1328:1370	the necrotic debris-induced IL-1β secretion	1328:1370	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	4	23	theme	severe	751:756	arg1	hypoxia					758:764	persistent and severe hypoxia	736:764	persistent and severe hypoxia	736:764	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	2	24	theme	critical	313:320	arg1	factors					322:328	two critical factors	309:328	two critical factors that shape the HCC microenvironment	309:364	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	2	24	theme	critical	313:320	arg1	inflammation					292:303	inflammation	292:303	inflammation	292:303	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	2	24	theme	critical	313:320	arg1	Hypoxia					280:286	Hypoxia	280:286	Hypoxia	280:286	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	4	25	with	macrophages	863:873	arg1	phenotype					886:894	an M2 phenotype	880:894	an M2 phenotype	880:894	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	11	26	dep	2018	2083:2086	arg1	67:1872-1889					2088:2099	67:1872-1889	2088:2099	67:1872-1889	2088:2099	(Hepatology 2018;67:1872-1889).
29171040	1	27	theme	hepatocellular	204:217	arg1	HCC					230:232	HCC	230:232	HCC	230:232	The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment.
29171040	1	27	theme	hepatocellular	204:217	arg1	carcinoma					219:227	hepatocellular carcinoma	204:227	hepatocellular carcinoma (HCC)	204:233	The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment.
29171040	4	28	theme	IL-1β	829:833	arg1	release					835:841	potent IL-1β release	822:841	potent IL-1β release	822:841	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	2	29	theme	such	456:459	arg1	conditions					461:470	such conditions	456:470	such conditions	456:470	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	5	30	theme	B	1116:1116	arg1	cells					1118:1122	activated B cells	1106:1122	activated B cells	1106:1122	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	10	31	theme	cancer	1813:1818	arg1	cells					1820:1824	cancer cells	1813:1824	cancer cells	1813:1824	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	0	32	theme	Hypoxia-inducible	0:16	arg1	signaling					43:51	Hypoxia-inducible factor-1α/interleukin-1β signaling	0:51	Hypoxia-inducible factor-1α/interleukin-1β signaling	0:51	Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment.
29171040	5	33	theme	adapter-inducing	1031:1046	arg1	kappa-light-chain-enhancer					1076:1101	adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer	1031:1101	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	4	34	theme	HCC	804:806	arg1	cells					808:812	HCC cells	804:812	HCC cells	804:812	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	3	35	theme	interleukin	605:615	arg1	IL-1β					621:625	IL-1β	621:625	IL-1β	621:625	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	3	35	theme	interleukin	605:615	arg1	1β					617:618	more interleukin 1β	600:618	more interleukin 1β (IL-1β)	600:626	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	5	36	theme	factor	1069:1074	arg1	kappa-light-chain-enhancer					1076:1101	adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer	1031:1101	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	7	37	theme	HIF-1α	1453:1458	arg1	synthesis					1440:1448	the synthesis	1436:1448	the synthesis of HIF-1α	1436:1458	Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells through cyclooxygenase-2.
29171040	10	38	theme	HCC	2056:2058	arg1	treatment					2060:2068	HCC treatment	2056:2068	HCC treatment	2056:2068	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	3	39	theme	tumor-associated	512:527	arg1	cells					570:574	the primary proinflammatory cells	542:574	the primary proinflammatory cells within tumors	542:588	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	3	39	theme	tumor-associated	512:527	arg1	macrophages					529:539	tumor-associated macrophages	512:539	tumor-associated macrophages	512:539	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	0	40	theme	hepatoma	62:69	arg1	transition					94:103	hepatoma epithelial-mesenchymal transition	62:103	hepatoma epithelial-mesenchymal transition	62:103	Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment.
29171040	10	41	theme	strategy	2044:2051	arg1	role					2015:2018	a potential role	2003:2018	a potential role of an anti-inflammatory strategy in HCC treatment	2003:2068	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	8	42	theme	cells	1570:1574	arg1	transition					1552:1561	The epithelial-mesenchymal transition	1525:1561	The epithelial-mesenchymal transition of HCC cells	1525:1574	The epithelial-mesenchymal transition of HCC cells was enhanced by overexpression of HIF-1α.
29171040	3	43	theme	primary	546:552	arg1	cells					570:574	the primary proinflammatory cells	542:574	the primary proinflammatory cells within tumors	542:588	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	3	43	theme	primary	546:552	arg1	macrophages					529:539	tumor-associated macrophages	512:539	tumor-associated macrophages	512:539	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	7	44	theme	local	1412:1416	arg1	microenvironment					1418:1433	the local microenvironment	1408:1433	the local microenvironment	1408:1433	Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells through cyclooxygenase-2.
29171040	10	45	theme	epithelial-mesenchymal	1915:1936	arg1	transition					1938:1947	epithelial-mesenchymal transition	1915:1947	epithelial-mesenchymal transition	1915:1947	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	10	46	theme	cancer	1903:1908	arg1	cell					1910:1913	cancer cell epithelial-mesenchymal transition and metastasis	1903:1962	cell	1910:1913	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	7	47	from	increase	1387:1394	arg1	microenvironment					1418:1433	the local microenvironment	1408:1433	the local microenvironment	1408:1433	Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells through cyclooxygenase-2.
29171040	6	48	theme	mass	1225:1228	arg1	spectrometry					1230:1241	mass spectrometry	1225:1241	mass spectrometry	1225:1241	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	2	49	theme	HCC	345:347	arg1	microenvironment					349:364	the HCC microenvironment	341:364	the HCC microenvironment	341:364	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	3	50	theme	moderate	634:641	arg1	conditions					651:660	moderate hypoxic conditions	634:660	moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α)	634:727	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	5	51	from	signaling	1124:1132	arg1	fashion					1167:1173	a similar, but not identical, fashion	1137:1173	a similar, but not identical, fashion	1137:1173	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	5	52	theme	necrotic	927:934	arg1	secretion					957:965	the necrotic debris-induced IL-1β secretion	923:965	the necrotic debris-induced IL-1β secretion	923:965	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	6	53	theme	O-linked	1283:1290	arg1	glycosylation					1292:1304	O-linked glycosylation	1283:1304	O-linked glycosylation	1283:1304	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	4	54	theme	M2	883:884	arg1	phenotype					886:894	an M2 phenotype	880:894	an M2 phenotype	880:894	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	1	55	theme	local	256:260	arg1	microenvironment					262:277	its local microenvironment	252:277	its local microenvironment	252:277	The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment.
29171040	8	56	theme	HIF-1α	1610:1615	arg1	overexpression					1592:1605	overexpression	1592:1605	overexpression of HIF-1α	1592:1615	The epithelial-mesenchymal transition of HCC cells was enhanced by overexpression of HIF-1α.
29171040	6	57	theme	proteins	1269:1276	arg1	proteins					1269:1276	proteins	1269:1276	proteins with O-linked glycosylation	1269:1304	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	6	57	theme	proteins	1269:1276	arg1	group					1260:1264	a group	1258:1264	a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion	1258:1370	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	1	58	theme	carcinoma	219:227	arg1	progression					189:199	progression	189:199	progression	189:199	The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment.
29171040	1	58	theme	carcinoma	219:227	arg1	development					173:183	development	173:183	development	173:183	The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment.
29171040	10	59	theme	potential	2005:2013	arg1	role					2015:2018	a potential role	2003:2018	a potential role of an anti-inflammatory strategy in HCC treatment	2003:2068	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	10	60	theme	HIF-1α/IL-1β	1777:1788	arg1	loop					1800:1803	an HIF-1α/IL-1β signaling loop	1774:1803	an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages	1774:1857	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	3	61	theme	hypoxia	692:698	arg1	factor					710:715	hypoxia inducible factor 1α	692:718	hypoxia inducible factor 1α (HIF-1α)	692:727	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	3	61	theme	hypoxia	692:698	arg1	HIF-1α					721:726	HIF-1α	721:726	HIF-1α	721:726	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	5	62	theme	receptor	998:1005	arg1	signaling					1124:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling	988:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	6	63	theme	debris-induced	1341:1354	arg1	secretion					1362:1370	the necrotic debris-induced IL-1β secretion	1328:1370	the necrotic debris-induced IL-1β secretion	1328:1370	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	9	64	theme	mouse	1674:1678	arg1	models					1680:1685	mouse models	1674:1685	mouse models	1674:1685	We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients.
29171040	5	65	theme	IL-1β	951:955	arg1	secretion					957:965	the necrotic debris-induced IL-1β secretion	923:965	the necrotic debris-induced IL-1β secretion	923:965	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	7	66	theme	HCC	1489:1491	arg1	cells					1493:1497	HCC cells	1489:1497	HCC cells	1489:1497	Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells through cyclooxygenase-2.
29171040	1	67	dep	development	173:183	arg1	The					169:171	The	169:171	The	169:171	The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment.
29171040	0	68	theme	hypoxic-inflammatory	130:149	arg1	microenvironment					151:166	a hypoxic-inflammatory microenvironment	128:166	a hypoxic-inflammatory microenvironment	128:166	Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment.
29171040	9	69	from	prognosis	1714:1722	arg1	patients					1731:1738	HCC patients	1727:1738	HCC patients	1727:1738	We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients.
29171040	5	70	theme	kappa-light-chain-enhancer	1076:1101	arg1	signaling					1124:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling	988:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	4	71	theme	cells	808:812	arg1	debris					794:799	the necrotic debris	781:799	the necrotic debris of HCC cells	781:812	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	6	72	link	O-linked	1283:1290	arg1	glycosylation					1292:1304	O-linked glycosylation	1283:1304	O-linked glycosylation	1283:1304	Using mass spectrometry, we identified a group of proteins with O-linked glycosylation to be responsible for the necrotic debris-induced IL-1β secretion.
29171040	5	73	theme	activated	1106:1114	arg1	cells					1118:1122	activated B cells	1106:1122	activated B cells	1106:1122	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	4	74	theme	potent	822:827	arg1	release					835:841	potent IL-1β release	822:841	potent IL-1β release	822:841	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	0	75	theme	factor-1α/interleukin-1β	18:41	arg1	signaling					43:51	Hypoxia-inducible factor-1α/interleukin-1β signaling	0:51	Hypoxia-inducible factor-1α/interleukin-1β signaling	0:51	Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment.
29171040	5	76	theme	domain-containing	1013:1029	arg1	signaling					1124:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling	988:1132	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	11	77	theme	Hepatology	2072:2081	arg1	2018					2083:2086	Hepatology 2018	2072:2086	Hepatology 2018;67:1872-1889	2072:2099	(Hepatology 2018;67:1872-1889).
29171040	4	78	theme	necrotic	785:792	arg1	debris					794:799	the necrotic debris	781:799	the necrotic debris of HCC cells	781:812	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	2	79	theme	cancer	437:442	arg1	cells					444:448	cancer cells	437:448	cancer cells	437:448	Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood.
29171040	5	80	theme	interferon-β/nuclear	1048:1067	arg1	kappa-light-chain-enhancer					1076:1101	adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer	1031:1101	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	10	81	from	role	2015:2018	arg1	treatment					2060:2068	HCC treatment	2056:2068	HCC treatment	2056:2068	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	9	82	theme	poor	1709:1712	arg1	prognosis					1714:1722	poor prognosis	1709:1722	poor prognosis in HCC patients	1709:1738	We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients.
29171040	10	83	dep	cell	1910:1913	arg1	transition					1938:1947	epithelial-mesenchymal transition	1915:1947	epithelial-mesenchymal transition	1915:1947	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	0	84	theme	epithelial-mesenchymal	71:92	arg1	transition					94:103	hepatoma epithelial-mesenchymal transition	62:103	hepatoma epithelial-mesenchymal transition	62:103	Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment.
29171040	5	85	theme	similar	1139:1145	arg1	fashion					1167:1173	a similar, but not identical, fashion	1137:1173	a similar, but not identical, fashion	1137:1173	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	3	86	theme	factor	710:715	arg1	stability					679:687	increased stability	669:687	increased stability of hypoxia inducible factor 1α (HIF-1α)	669:727	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	10	87	theme	tumor-associated	1830:1845	arg1	macrophages					1847:1857	tumor-associated macrophages	1830:1857	tumor-associated macrophages	1830:1857	CONCLUSION Our findings revealed an HIF-1α/IL-1β signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in HCC treatment.
29171040	8	88	theme	HCC	1566:1568	arg1	cells					1570:1574	HCC cells	1566:1574	HCC cells	1566:1574	The epithelial-mesenchymal transition of HCC cells was enhanced by overexpression of HIF-1α.
29171040	5	89	theme	cells	1118:1122	arg1	kappa-light-chain-enhancer					1076:1101	adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer	1031:1101	Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation	988:1216	We further confirmed that the necrotic debris-induced IL-1β secretion was mediated through Toll-like receptor 4/TIR domain-containing adapter-inducing interferon-β/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide-induced inflammation.
29171040	9	90	theme	prognosis	1714:1722	arg1	predictive					1695:1704	predictive	1695:1704	predictive	1695:1704	We further showed that IL-1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients.
29171040	3	91	theme	proinflammatory	554:568	arg1	cells					570:574	the primary proinflammatory cells	542:574	the primary proinflammatory cells within tumors	542:588	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	3	91	theme	proinflammatory	554:568	arg1	macrophages					529:539	tumor-associated macrophages	512:539	tumor-associated macrophages	512:539	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	7	92	theme	IL-1β	1399:1403	arg1	increase					1387:1394	the increase	1383:1394	the increase of IL-1β in the local microenvironment	1383:1433	Following the increase of IL-1β in the local microenvironment, the synthesis of HIF-1α was up-regulated by IL-1β in HCC cells through cyclooxygenase-2.
29171040	4	93	theme	tumor-associated	846:861	arg1	macrophages					863:873	tumor-associated macrophages	846:873	tumor-associated macrophages with an M2 phenotype	846:894	Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL-1β release by tumor-associated macrophages with an M2 phenotype.
29171040	3	94	theme	more	600:603	arg1	IL-1β					621:625	IL-1β	621:625	IL-1β	621:625	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
29171040	3	94	theme	more	600:603	arg1	1β					617:618	more interleukin 1β	600:618	more interleukin 1β (IL-1β)	600:626	We found that tumor-associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL-1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF-1α).
28408270	0	0	theme	deletion	86:93	arg1	impact					62:67	impact	62:67	impact of GtfA and GtfB deletion on PsrP-associated virulence properties	62:133	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	0	0	theme	deletion	86:93	arg1	organization					16:27	Transcriptional organization	0:27	Transcriptional organization of pneumococcal psrP-secY2A2	0:56	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	9	1	from	pneumonia	1466:1474	arg1	mice					1479:1482	mice	1479:1482	mice	1479:1482	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	10	2	theme	PsrP-mediated	1607:1619	arg1	virulence					1634:1642	PsrP-mediated pneumococcal virulence	1607:1642	PsrP-mediated pneumococcal virulence	1607:1642	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	9	3	theme	biofilm	1408:1414	arg1	formation					1416:1424	biofilm formation	1408:1424	biofilm formation	1408:1424	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	4	4	theme	operons	610:616	arg1	Transcription					583:595	Transcription	583:595	Transcription of all three operons	583:616	Transcription of all three operons was greatest during biofilm growth and immunoblot analyses confirmed increased PsrP production by biofilm pneumococci.
28408270	0	5	theme	GtfB	81:84	arg1	deletion					86:93	GtfB deletion	81:93	GtfB deletion	81:93	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	0	6	from	organization	16:27	arg1	properties					124:133	PsrP-associated virulence properties	98:133	PsrP-associated virulence properties	98:133	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	10	7	theme	indispensable	1568:1580	arg1	role					1582:1585	the indispensable role	1564:1585	the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence	1564:1642	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	2	8	theme	pathogenicity	382:394	arg1	island					396:401	the 37-kbp pathogenicity island	371:401	the 37-kbp pathogenicity island encoding PsrP and its accessory genes	371:439	Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes.
28408270	2	8	theme	pathogenicity	382:394	arg1	psrP-secY2A2					357:368	psrP-secY2A2	357:368	psrP-secY2A2	357:368	Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes.
28408270	1	9	theme	biofilm	278:284	arg1	formation					286:294	biofilm formation	278:294	biofilm formation	278:294	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	0	10	theme	PsrP-associated	98:112	arg1	properties					124:133	PsrP-associated virulence properties	98:133	PsrP-associated virulence properties	98:133	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	6	11	theme	carbohydrate	992:1003	arg1	specificities					1005:1017	known carbohydrate specificities	986:1017	known carbohydrate specificities	986:1017	This finding was validated by immunoblot using lectins with known carbohydrate specificities.
28408270	10	12	theme	psrP-secY2A2	1542:1553	arg1	organization					1526:1537	the transcriptional organization	1506:1537	the transcriptional organization of psrP-secY2A2	1506:1553	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	6	13	theme	known	986:990	arg1	specificities					1005:1017	known carbohydrate specificities	986:1017	known carbohydrate specificities	986:1017	This finding was validated by immunoblot using lectins with known carbohydrate specificities.
28408270	1	14	gly	glycoprotein	188:199	arg1	glycoprotein					188:199	a glycoprotein	186:199	a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation	186:294	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	1	14	gly	glycoprotein	188:199	arg1	protein					168:174	Pneumococcal serine-rich repeat protein	136:174	Pneumococcal serine-rich repeat protein (PsrP)	136:181	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	10	15	theme	GtfB	1599:1602	arg1	role					1582:1585	the indispensable role	1564:1585	the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence	1564:1642	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	1	16	theme	repeat	161:166	arg1	glycoprotein					188:199	a glycoprotein	186:199	a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation	186:294	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	1	16	theme	repeat	161:166	arg1	PsrP					177:180	PsrP	177:180	PsrP	177:180	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	1	16	theme	repeat	161:166	arg1	protein					168:174	Pneumococcal serine-rich repeat protein	136:174	Pneumococcal serine-rich repeat protein (PsrP)	136:181	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	8	17	theme	whole	1282:1286	arg1	lysates					1293:1299	bacterial whole cell lysates	1272:1299	bacterial whole cell lysates	1272:1299	These deletions negatively affected our ability to detect PsrP1-734 in bacterial whole cell lysates.
28408270	0	18	from	impact	62:67	arg1	properties					124:133	PsrP-associated virulence properties	98:133	PsrP-associated virulence properties	98:133	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	4	19	theme	immunoblot	657:666	arg1	analyses					668:675	immunoblot analyses	657:675	immunoblot analyses	657:675	Transcription of all three operons was greatest during biofilm growth and immunoblot analyses confirmed increased PsrP production by biofilm pneumococci.
28408270	4	20	theme	biofilm	716:722	arg1	pneumococci					724:734	biofilm pneumococci	716:734	biofilm pneumococci	716:734	Transcription of all three operons was greatest during biofilm growth and immunoblot analyses confirmed increased PsrP production by biofilm pneumococci.
28408270	3	21	theme	RNA-seq	472:478	arg1	analysis					480:487	RNA-seq analysis	472:487	RNA-seq analysis	472:487	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	0	22	theme	virulence	114:122	arg1	properties					124:133	PsrP-associated virulence properties	98:133	PsrP-associated virulence properties	98:133	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	9	23	theme	S.	1312:1313	arg1	mutants					1326:1332	S. pneumoniae mutants	1312:1332	S. pneumoniae mutants lacking these genes	1312:1352	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	10	24	theme	GtfA	1590:1593	arg1	role					1582:1585	the indispensable role	1564:1585	the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence	1564:1642	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	5	25	theme	PsrP	904:907	arg1	version					893:899	a recombinant intracellular version	865:899	a recombinant intracellular version	865:899	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	2	26	theme	accessory	425:433	arg1	genes					435:439	its accessory genes	421:439	its accessory genes	421:439	Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes.
28408270	7	27	theme	associated	1168:1177	arg1	properties					1189:1198	its associated virulence properties	1164:1198	its associated virulence properties	1164:1198	We subsequently deleted gtfA and gtfB, the GTFs thought to be responsible for addition of O-linked N-acetylglucosamine, and tested for PsrP and its associated virulence properties.
28408270	4	28	theme	PsrP	697:700	arg1	production					702:711	increased PsrP production	687:711	increased PsrP production by biofilm pneumococci	687:734	Transcription of all three operons was greatest during biofilm growth and immunoblot analyses confirmed increased PsrP production by biofilm pneumococci.
28408270	3	29	dep	operons	542:548	arg1	glyB					562:565	glyB	562:565	glyB	562:565	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	3	29	dep	operons	542:548	arg1	glyC-asp5					572:580	glyC-asp5	572:580	glyC-asp5	572:580	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	3	29	dep	operons	542:548	arg1	psrP-glyA					551:559	psrP-glyA	551:559	psrP-glyA	551:559	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	3	29	dep	operons	542:548	arg1	operons					542:548	three operons	536:548	three operons: psrP-glyA, glyB, and glyC-asp5	536:580	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	3	30	theme	cDNA	463:466	arg1	amplification					446:458	PCR amplification	442:458	PCR amplification of cDNA and RNA-seq analysis	442:487	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	0	31	theme	Transcriptional	0:14	arg1	organization					16:27	Transcriptional organization	0:27	Transcriptional organization of pneumococcal psrP-secY2A2	0:56	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	7	32	theme	virulence	1179:1187	arg1	properties					1189:1198	its associated virulence properties	1164:1198	its associated virulence properties	1164:1198	We subsequently deleted gtfA and gtfB, the GTFs thought to be responsible for addition of O-linked N-acetylglucosamine, and tested for PsrP and its associated virulence properties.
28408270	9	33	theme	pneumoniae	1315:1324	arg1	mutants					1326:1332	S. pneumoniae mutants	1312:1332	S. pneumoniae mutants lacking these genes	1312:1352	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	0	34	theme	pneumococcal	32:43	arg1	psrP-secY2A2					45:56	pneumococcal psrP-secY2A2	32:56	pneumococcal psrP-secY2A2	32:56	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	9	35	theme	lung	1439:1442	arg1	cells					1455:1459	lung epithelial cells	1439:1459	lung epithelial cells	1439:1459	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	5	36	theme	chromatography-mass	747:765	arg1	spectrometry					767:778	gas chromatography-mass spectrometry	743:778	gas chromatography-mass spectrometry	743:778	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	2	37	theme	transcriptional	325:339	arg1	organization					341:352	the transcriptional organization	321:352	the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes	321:439	Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes.
28408270	9	38	from	formation	1416:1424	arg1	mice					1479:1482	mice	1479:1482	mice	1479:1482	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	9	39	theme	epithelial	1444:1453	arg1	cells					1455:1459	lung epithelial cells	1439:1459	lung epithelial cells	1439:1459	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	9	40	from	adhesion	1427:1434	arg1	mice					1479:1482	mice	1479:1482	mice	1479:1482	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	10	41	from	role	1582:1585	arg1	virulence					1634:1642	PsrP-mediated pneumococcal virulence	1607:1642	PsrP-mediated pneumococcal virulence	1607:1642	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	1	42	theme	Streptococcus	215:227	arg1	attachment					240:249	Streptococcus pneumoniae attachment	215:249	Streptococcus pneumoniae attachment to lung cells	215:263	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	10	43	theme	transcriptional	1510:1524	arg1	organization					1526:1537	the transcriptional organization	1506:1537	the transcriptional organization of psrP-secY2A2	1506:1553	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	4	44	theme	increased	687:695	arg1	production					702:711	increased PsrP production	687:711	increased PsrP production by biofilm pneumococci	687:734	Transcription of all three operons was greatest during biofilm growth and immunoblot analyses confirmed increased PsrP production by biofilm pneumococci.
28408270	0	45	theme	psrP-secY2A2	45:56	arg1	impact					62:67	impact	62:67	impact of GtfA and GtfB deletion on PsrP-associated virulence properties	62:133	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	0	45	theme	psrP-secY2A2	45:56	arg1	organization					16:27	Transcriptional organization	0:27	Transcriptional organization of pneumococcal psrP-secY2A2	0:56	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	5	46	theme	recombinant	867:877	arg1	version					893:899	a recombinant intracellular version	865:899	a recombinant intracellular version	865:899	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	8	47	theme	bacterial	1272:1280	arg1	lysates					1293:1299	bacterial whole cell lysates	1272:1299	bacterial whole cell lysates	1272:1299	These deletions negatively affected our ability to detect PsrP1-734 in bacterial whole cell lysates.
28408270	5	48	theme	intracellular	879:891	arg1	version					893:899	a recombinant intracellular version	865:899	a recombinant intracellular version	865:899	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	5	49	theme	monomeric	794:802	arg1	present					854:860	the primary glycoconjugate present	827:860	the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734	827:923	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	5	49	theme	monomeric	794:802	arg1	N-acetylglucosamine					804:822	monomeric N-acetylglucosamine	794:822	monomeric N-acetylglucosamine	794:822	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	5	50	theme	glycoconjugate	839:852	arg1	present					854:860	the primary glycoconjugate present	827:860	the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734	827:923	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	5	50	theme	glycoconjugate	839:852	arg1	N-acetylglucosamine					804:822	monomeric N-acetylglucosamine	794:822	monomeric N-acetylglucosamine	794:822	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	7	51	theme	O-linked	1110:1117	arg1	N-acetylglucosamine					1119:1137	O-linked N-acetylglucosamine	1110:1137	O-linked N-acetylglucosamine	1110:1137	We subsequently deleted gtfA and gtfB, the GTFs thought to be responsible for addition of O-linked N-acetylglucosamine, and tested for PsrP and its associated virulence properties.
28408270	2	52	theme	37-kbp	375:380	arg1	island					396:401	the 37-kbp pathogenicity island	371:401	the 37-kbp pathogenicity island encoding PsrP and its accessory genes	371:439	Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes.
28408270	2	52	theme	37-kbp	375:380	arg1	psrP-secY2A2					357:368	psrP-secY2A2	357:368	psrP-secY2A2	357:368	Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes.
28408270	3	53	theme	PCR	442:444	arg1	amplification					446:458	PCR amplification	442:458	PCR amplification of cDNA and RNA-seq analysis	442:487	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	5	54	from	present	854:860	arg1	version					893:899	a recombinant intracellular version	865:899	a recombinant intracellular version	865:899	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	1	55	theme	Pneumococcal	136:147	arg1	glycoprotein					188:199	a glycoprotein	186:199	a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation	186:294	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	1	55	theme	Pneumococcal	136:147	arg1	PsrP					177:180	PsrP	177:180	PsrP	177:180	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	1	55	theme	Pneumococcal	136:147	arg1	protein					168:174	Pneumococcal serine-rich repeat protein	136:174	Pneumococcal serine-rich repeat protein (PsrP)	136:181	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	7	56	link	O-linked	1110:1117	arg1	N-acetylglucosamine					1119:1137	O-linked N-acetylglucosamine	1110:1137	O-linked N-acetylglucosamine	1110:1137	We subsequently deleted gtfA and gtfB, the GTFs thought to be responsible for addition of O-linked N-acetylglucosamine, and tested for PsrP and its associated virulence properties.
28408270	7	57	theme	N-acetylglucosamine	1119:1137	arg1	addition					1098:1105	addition	1098:1105	addition of O-linked N-acetylglucosamine	1098:1137	We subsequently deleted gtfA and gtfB, the GTFs thought to be responsible for addition of O-linked N-acetylglucosamine, and tested for PsrP and its associated virulence properties.
28408270	9	58	theme	psrP	1371:1374	arg1	mutant					1376:1381	the psrP mutant	1367:1381	the psrP mutant	1367:1381	Moreover, S. pneumoniae mutants lacking these genes pheno-copied the psrP mutant and were attenuated for: biofilm formation, adhesion to lung epithelial cells, and pneumonia in mice.
28408270	1	59	theme	serine-rich	149:159	arg1	glycoprotein					188:199	a glycoprotein	186:199	a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation	186:294	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	1	59	theme	serine-rich	149:159	arg1	PsrP					177:180	PsrP	177:180	PsrP	177:180	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	1	59	theme	serine-rich	149:159	arg1	protein					168:174	Pneumococcal serine-rich repeat protein	136:174	Pneumococcal serine-rich repeat protein (PsrP)	136:181	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	4	60	theme	biofilm	638:644	arg1	growth					646:651	biofilm growth	638:651	biofilm growth	638:651	Transcription of all three operons was greatest during biofilm growth and immunoblot analyses confirmed increased PsrP production by biofilm pneumococci.
28408270	5	61	theme	gas	743:745	arg1	spectrometry					767:778	gas chromatography-mass spectrometry	743:778	gas chromatography-mass spectrometry	743:778	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	8	62	theme	cell	1288:1291	arg1	lysates					1293:1299	bacterial whole cell lysates	1272:1299	bacterial whole cell lysates	1272:1299	These deletions negatively affected our ability to detect PsrP1-734 in bacterial whole cell lysates.
28408270	2	63	theme	psrP-secY2A2	357:368	arg1	organization					341:352	the transcriptional organization	321:352	the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes	321:439	Herein, we investigated the transcriptional organization of psrP-secY2A2, the 37-kbp pathogenicity island encoding PsrP and its accessory genes.
28408270	1	64	theme	lung	254:257	arg1	cells					259:263	lung cells	254:263	lung cells	254:263	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	5	65	theme	primary	831:837	arg1	present					854:860	the primary glycoconjugate present	827:860	the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734	827:923	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	5	65	theme	primary	831:837	arg1	N-acetylglucosamine					804:822	monomeric N-acetylglucosamine	794:822	monomeric N-acetylglucosamine	794:822	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	8	66	from	PsrP1-734	1259:1267	arg1	lysates					1293:1299	bacterial whole cell lysates	1272:1299	bacterial whole cell lysates	1272:1299	These deletions negatively affected our ability to detect PsrP1-734 in bacterial whole cell lysates.
28408270	5	67	dep	PsrP1-734	915:923	arg1	i.e.					910:913	i.e.	910:913	i.e.	910:913	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
28408270	10	68	theme	pneumococcal	1621:1632	arg1	virulence					1634:1642	PsrP-mediated pneumococcal virulence	1607:1642	PsrP-mediated pneumococcal virulence	1607:1642	Our studies identify the transcriptional organization of psrP-secY2A2 and show the indispensable role of GtfA and GtfB on PsrP-mediated pneumococcal virulence.
28408270	6	69	with	lectins	973:979	arg1	specificities					1005:1017	known carbohydrate specificities	986:1017	known carbohydrate specificities	986:1017	This finding was validated by immunoblot using lectins with known carbohydrate specificities.
28408270	3	70	theme	analysis	480:487	arg1	amplification					446:458	PCR amplification	442:458	PCR amplification of cDNA and RNA-seq analysis	442:487	PCR amplification of cDNA and RNA-seq analysis found psrP-secY2A2 to be minimally composed of three operons: psrP-glyA, glyB, and glyC-asp5.
28408270	0	71	theme	GtfA	72:75	arg1	impact					62:67	impact	62:67	impact of GtfA and GtfB deletion on PsrP-associated virulence properties	62:133	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	0	71	theme	GtfA	72:75	arg1	organization					16:27	Transcriptional organization	0:27	Transcriptional organization of pneumococcal psrP-secY2A2	0:56	Transcriptional organization of pneumococcal psrP-secY2A2 and impact of GtfA and GtfB deletion on PsrP-associated virulence properties.
28408270	1	72	dep	Streptococcus	215:227	arg1	pneumoniae					229:238	pneumoniae	229:238	pneumoniae	229:238	Pneumococcal serine-rich repeat protein (PsrP) is a glycoprotein that mediates Streptococcus pneumoniae attachment to lung cells and promotes biofilm formation.
28408270	5	73	dep	identified	783:792	arg1	Using					737:741	Using	737:741	Using gas chromatography-mass spectrometry	737:778	Using gas chromatography-mass spectrometry we identified monomeric N-acetylglucosamine as the primary glycoconjugate present on a recombinant intracellular version of PsrP, i.e. PsrP1-734.
31588002	7	0	theme	hippocampal	1182:1192	arg1	neurons					1194:1200	mature hippocampal neurons	1175:1200	mature hippocampal neurons using a viral-mediated approach	1175:1232	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	5	1	from	impairments	910:920	arg1	mice					930:933	aged mice	925:933	aged mice	925:933	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	8	2	theme	spatial	1408:1414	arg1	learning					1416:1423	spatial learning	1408:1423	spatial learning	1408:1423	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	4	3	from	role	714:717	arg1	aging					742:746	physiological brain aging	722:746	physiological brain aging	722:746	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
31588002	6	4	theme	knockout	1057:1064	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	4	theme	knockout	1057:1064	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	4	5	from	role	631:634	arg1	conditions					669:678	neurodegenerative conditions	651:678	neurodegenerative conditions	651:678	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
31588002	4	5	from	role	631:634	arg1	disease					701:707	Alzheimer's disease	689:707	Alzheimer's disease	689:707	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
31588002	1	6	theme	cognitive	166:174	arg1	functions					176:184	cellular and cognitive functions	153:184	cellular and cognitive functions in the aging brain	153:203	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	2	7	from	effects	317:323	arg1	hippocampus					382:392	the hippocampus	378:392	the hippocampus	378:392	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	2	7	from	effects	317:323	arg1	regions					348:354	vulnerable regions	337:354	vulnerable regions	337:354	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	6	8	theme	conditional	1045:1055	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	8	theme	conditional	1045:1055	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	7	9	theme	adult	1276:1280	arg1	mice					1282:1285	young adult mice	1270:1285	young adult mice	1270:1285	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	6	10	theme	aged	949:952	arg1	condition					954:962	an aged condition	946:962	an aged condition in young adults	946:978	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	5	11	theme	decreased	820:828	arg1	expression					857:866	age-related decreased O-GlcNAc transferase (OGT) expression	808:866	age-related decreased O-GlcNAc transferase (OGT) expression	808:866	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	6	12	theme	neuron-specific	1029:1043	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	12	theme	neuron-specific	1029:1043	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	7	13	theme	young	1270:1274	arg1	mice					1282:1285	young adult mice	1270:1285	young adult mice	1270:1285	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	7	14	theme	mature	1175:1180	arg1	neurons					1194:1200	mature hippocampal neurons	1175:1200	mature hippocampal neurons using a viral-mediated approach	1175:1232	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	2	15	theme	molecular	282:290	arg1	targets					292:298	molecular targets	282:298	molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus	282:392	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	5	16	theme	cognitive	900:908	arg1	impairments					910:920	cognitive impairments	900:920	cognitive impairments in aged mice	900:933	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	4	17	theme	brain	736:740	arg1	aging					742:746	physiological brain aging	722:746	physiological brain aging	722:746	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
31588002	7	18	theme	overexpressing	1153:1166	arg1	OGT					1168:1170	overexpressing OGT	1153:1170	overexpressing OGT in mature hippocampal neurons using a viral-mediated approach	1153:1232	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	6	19	theme	cognitive	1106:1114	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	19	theme	cognitive	1106:1114	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	3	20	theme	synaptic	545:552	arg1	alterations					554:564	aging-specific synaptic alterations	530:564	aging-specific synaptic alterations as well as neurodegeneration	530:593	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	6	21	theme	brain	1128:1132	arg1	aging					1134:1138	brain aging	1128:1138	brain aging	1128:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	1	22	theme	functions	176:184	arg1	rejuvenation					137:148	rejuvenation	137:148	rejuvenation of cellular and cognitive functions in the aging brain	137:203	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	6	23	theme	controlled	1018:1027	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	23	theme	controlled	1018:1027	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	1	24	theme	Mounting	78:85	arg1	evidence					87:94	Mounting evidence	78:94	Mounting evidence in animal models	78:111	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	6	25	theme	aging	1134:1138	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	25	theme	aging	1134:1138	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	5	26	theme	transferase	839:849	arg1	expression					857:866	age-related decreased O-GlcNAc transferase (OGT) expression	808:866	age-related decreased O-GlcNAc transferase (OGT) expression	808:866	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	7	27	from	memory	1260:1265	arg1	mice					1282:1285	young adult mice	1270:1285	young adult mice	1270:1285	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	3	28	link	O-linked	439:446	arg1	O-GlcNAc					469:476	O-GlcNAc	469:476	O-GlcNAc	469:476	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	3	28	link	O-linked	439:446	arg1	N-Acetylglucosamine					448:466	O-linked N-Acetylglucosamine	439:466	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc)	395:477	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	1	29	from	rejuvenation	137:148	arg1	brain					199:203	the aging brain	189:203	the aging brain	189:203	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	7	30	theme	fear	1255:1258	arg1	memory					1260:1265	associative fear memory	1243:1265	associative fear memory in young adult mice	1243:1285	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	3	31	theme	post-translational	407:424	arg1	modification					426:437	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc)	395:477	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc)	395:477	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	0	32	theme	Neuronal	0:7	arg1	O-GlcNAcylation					9:23	Neuronal O-GlcNAcylation	0:23	Neuronal O-GlcNAcylation	0:23	Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain.
31588002	8	33	from	impairments	1393:1403	arg1	memory					1429:1434	memory	1429:1434	memory	1429:1434	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	8	33	from	impairments	1393:1403	arg1	learning					1416:1423	spatial learning	1408:1423	spatial learning	1408:1423	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	8	33	from	impairments	1393:1403	arg1	memory					1464:1469	associative fear memory	1447:1469	associative fear memory	1447:1469	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	1	34	theme	aging	193:197	arg1	brain					199:203	the aging brain	189:203	the aging brain	189:203	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	0	35	theme	Cognitive	34:42	arg1	Function					44:51	Cognitive Function	34:51	Cognitive Function	34:51	Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain.
31588002	9	36	theme	key	1510:1512	arg1	mediator					1524:1531	a key molecular mediator	1508:1531	a key molecular mediator promoting cognitive rejuvenation	1508:1564	Our data identify O-GlcNAcylaton as a key molecular mediator promoting cognitive rejuvenation.
31588002	9	36	theme	key	1510:1512	arg1	O-GlcNAcylaton					1490:1503	O-GlcNAcylaton	1490:1503	O-GlcNAcylaton	1490:1503	Our data identify O-GlcNAcylaton as a key molecular mediator promoting cognitive rejuvenation.
31588002	1	37	theme	animal	99:104	arg1	models					106:111	animal models	99:111	animal models	99:111	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	9	38	theme	cognitive	1543:1551	arg1	rejuvenation					1553:1564	cognitive rejuvenation	1543:1564	cognitive rejuvenation	1543:1564	Our data identify O-GlcNAcylaton as a key molecular mediator promoting cognitive rejuvenation.
31588002	7	39	theme	associative	1243:1253	arg1	memory					1260:1265	associative fear memory	1243:1265	associative fear memory in young adult mice	1243:1285	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	8	40	theme	associative	1447:1457	arg1	memory					1464:1469	associative fear memory	1447:1469	associative fear memory	1447:1469	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	4	41	theme	neurodegenerative	651:667	arg1	conditions					669:678	neurodegenerative conditions	651:678	neurodegenerative conditions	651:678	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
31588002	4	41	theme	neurodegenerative	651:667	arg1	disease					701:707	Alzheimer's disease	689:707	Alzheimer's disease	689:707	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
31588002	7	42	theme	viral-mediated	1210:1223	arg1	approach					1225:1232	a viral-mediated approach	1208:1232	a viral-mediated approach	1208:1232	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	4	43	theme	physiological	722:734	arg1	aging					742:746	physiological brain aging	722:746	physiological brain aging	722:746	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
31588002	5	44	theme	aged	925:928	arg1	mice					930:933	aged mice	925:933	aged mice	925:933	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	8	45	theme	aged	1348:1351	arg1	hippocampus					1353:1363	the aged hippocampus	1344:1363	the aged hippocampus	1344:1363	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	3	46	theme	dynamic	399:405	arg1	modification					426:437	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc)	395:477	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc)	395:477	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	5	47	theme	age-related	808:818	arg1	expression					857:866	age-related decreased O-GlcNAc transferase (OGT) expression	808:866	age-related decreased O-GlcNAc transferase (OGT) expression	808:866	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	8	48	theme	age-related	1381:1391	arg1	impairments					1393:1403	age-related impairments	1381:1403	age-related impairments in spatial learning and memory as well as associative fear memory	1381:1469	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	3	49	dep	modification	426:437	arg1	O-GlcNAc					469:476	O-GlcNAc	469:476	O-GlcNAc	469:476	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	3	49	dep	modification	426:437	arg1	N-Acetylglucosamine					448:466	O-linked N-Acetylglucosamine	439:466	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc)	395:477	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	6	50	theme	cellular	1093:1100	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	50	theme	cellular	1093:1100	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	0	51	theme	Aged	60:63	arg1	Brain					71:75	the Aged Mouse Brain	56:75	the Aged Mouse Brain	56:75	Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain.
31588002	9	52	theme	molecular	1514:1522	arg1	mediator					1524:1531	a key molecular mediator	1508:1531	a key molecular mediator promoting cognitive rejuvenation	1508:1564	Our data identify O-GlcNAcylaton as a key molecular mediator promoting cognitive rejuvenation.
31588002	9	52	theme	molecular	1514:1522	arg1	O-GlcNAcylaton					1490:1503	O-GlcNAcylaton	1490:1503	O-GlcNAcylaton	1490:1503	Our data identify O-GlcNAcylaton as a key molecular mediator promoting cognitive rejuvenation.
31588002	3	53	theme	O-linked	439:446	arg1	O-GlcNAc					469:476	O-GlcNAc	469:476	O-GlcNAc	469:476	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	3	53	theme	O-linked	439:446	arg1	N-Acetylglucosamine					448:466	O-linked N-Acetylglucosamine	439:466	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc)	395:477	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	2	54	theme	vulnerable	337:346	arg1	hippocampus					382:392	the hippocampus	378:392	the hippocampus	378:392	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	2	54	theme	vulnerable	337:346	arg1	regions					348:354	vulnerable regions	337:354	vulnerable regions	337:354	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	5	55	theme	O-GlcNAc	830:837	arg1	OGT					852:854	OGT	852:854	OGT	852:854	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	5	55	theme	O-GlcNAc	830:837	arg1	transferase					839:849	O-GlcNAc transferase	830:849	age-related decreased O-GlcNAc transferase (OGT) expression	808:866	Here, we report that countering age-related decreased O-GlcNAc transferase (OGT) expression and O-GlcNAcylation ameliorates cognitive impairments in aged mice.
31588002	1	56	from	brain	199:203	arg1	rejuvenation					137:148	rejuvenation	137:148	rejuvenation of cellular and cognitive functions in the aging brain	137:203	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	3	57	theme	attractive	497:506	arg1	target					508:513	an attractive target	494:513	an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration	494:593	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	8	58	theme	neuronal	1328:1335	arg1	OGT					1337:1339	neuronal OGT	1328:1339	neuronal OGT	1328:1339	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	2	59	theme	aging	328:332	arg1	effects					317:323	the effects	313:323	the effects of aging in vulnerable regions of the brain, such as the hippocampus	313:392	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	8	60	theme	fear	1459:1462	arg1	memory					1464:1469	associative fear memory	1447:1469	associative fear memory	1447:1469	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	6	61	theme	recapitulated	1079:1091	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	61	theme	recapitulated	1079:1091	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	7	62	from	OGT	1168:1170	arg1	neurons					1194:1200	mature hippocampal neurons	1175:1200	mature hippocampal neurons using a viral-mediated approach	1175:1232	Conversely, overexpressing OGT in mature hippocampal neurons using a viral-mediated approach enhanced associative fear memory in young adult mice.
31588002	3	63	theme	aging-specific	530:543	arg1	alterations					554:564	aging-specific synaptic alterations	530:564	aging-specific synaptic alterations as well as neurodegeneration	530:593	The dynamic post-translational modification O-linked N-Acetylglucosamine (O-GlcNAc) has emerged as an attractive target for regulating aging-specific synaptic alterations as well as neurodegeneration.
31588002	1	64	from	evidence	87:94	arg1	models					106:111	animal models	99:111	animal models	99:111	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	6	65	from	condition	954:962	arg1	adults					973:978	young adults	967:978	young adults	967:978	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	2	66	theme	brain	363:367	arg1	hippocampus					382:392	the hippocampus	378:392	the hippocampus	378:392	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	2	66	theme	brain	363:367	arg1	regions					348:354	vulnerable regions	337:354	vulnerable regions	337:354	However, the ability to utilize this potential is predicated on identifying molecular targets that reverse the effects of aging in vulnerable regions of the brain, such as the hippocampus.
31588002	8	67	theme	aged	1303:1306	arg1	mice					1308:1311	aged mice	1303:1311	aged mice overexpressing neuronal OGT in the aged hippocampus	1303:1363	Excitingly, in aged mice overexpressing neuronal OGT in the aged hippocampus rescued in part age-related impairments in spatial learning and memory as well as associative fear memory.
31588002	0	68	theme	Mouse	65:69	arg1	Brain					71:75	the Aged Mouse Brain	56:75	the Aged Mouse Brain	56:75	Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain.
31588002	6	69	theme	young	967:971	arg1	adults					973:978	young adults	967:978	young adults	967:978	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	70	theme	mouse	1066:1070	arg1	model					1072:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	a temporally controlled neuron-specific conditional knockout mouse model	1005:1076	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	6	70	theme	mouse	1066:1070	arg1	features					1116:1123	recapitulated cellular and cognitive features	1079:1123	recapitulated cellular and cognitive features of brain aging	1079:1138	Mimicking an aged condition in young adults by abrogating OGT, using a temporally controlled neuron-specific conditional knockout mouse model, recapitulated cellular and cognitive features of brain aging.
31588002	1	71	from	functions	176:184	arg1	brain					199:203	the aging brain	189:203	the aging brain	189:203	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	1	72	theme	cellular	153:160	arg1	functions					176:184	cellular and cognitive functions	153:184	cellular and cognitive functions in the aging brain	153:203	Mounting evidence in animal models indicates potential for rejuvenation of cellular and cognitive functions in the aging brain.
31588002	4	73	theme	O-GlcNAc	639:646	arg1	role					631:634	the role	627:634	the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease	627:707	While speculation exists about the role of O-GlcNAc in neurodegenerative conditions, such as Alzheimer's disease, its role in physiological brain aging remains largely unexplored.
28535613	0	0	theme	Recombinant	89:99	arg1	Cells					123:127	Recombinant Chinese Hamster Ovary Cells	89:127	Recombinant Chinese Hamster Ovary Cells	89:127	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	0	1	from	Purification	15:26	arg1	Cells					123:127	Recombinant Chinese Hamster Ovary Cells	89:127	Recombinant Chinese Hamster Ovary Cells	89:127	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	3	2	theme	furin	686:690	arg1	expression					692:701	recombinant furin expression	674:701	recombinant furin expression	674:701	The expression of the mature rhBMP-4 was significantly enhanced by recombinant furin expression.
28535613	5	3	theme	11-day	868:873	arg1	cultures					885:892	The 11-day fed-batch cultures	864:892	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor	864:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	2	4	theme	Chinese	468:474	arg1	line					502:505	a recombinant Chinese hamster ovary (rCHO) cell line	454:505	a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume)	454:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	8	5	theme	dose	1482:1485	arg1	concentration					1487:1499	an effective dose concentration	1469:1499	an effective dose concentration of EC50 of 2.93 ng/ml	1469:1521	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	2	6	theme	hamster	476:482	arg1	line					502:505	a recombinant Chinese hamster ovary (rCHO) cell line	454:505	a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume)	454:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	5	7	theme	fed-batch	875:883	arg1	cultures					885:892	The 11-day fed-batch cultures	864:892	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor	864:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	8	8	theme	EC50	1504:1507	arg1	concentration					1487:1499	an effective dose concentration	1469:1499	an effective dose concentration of EC50 of 2.93 ng/ml	1469:1521	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	0	9	theme	Hamster	109:115	arg1	Cells					123:127	Recombinant Chinese Hamster Ovary Cells	89:127	Recombinant Chinese Hamster Ovary Cells	89:127	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	0	10	from	Expression	0:9	arg1	Cells					123:127	Recombinant Chinese Hamster Ovary Cells	89:127	Recombinant Chinese Hamster Ovary Cells	89:127	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	2	11	theme	7.5-l	568:572	arg1	bioreactor					574:583	7.5-l bioreactor	568:583	7.5-l bioreactor (5 L working volume)	568:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	4	12	theme	defined	736:742	arg1	medium					744:749	a chemically defined medium	723:749	a chemically defined medium	723:749	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	7	13	gly	glycosylation	1268:1280	arg1	rhBMP-4					1298:1304	the purified rhBMP-4	1285:1304	the purified rhBMP-4	1285:1304	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	0	14	theme	Chinese	101:107	arg1	Cells					123:127	Recombinant Chinese Hamster Ovary Cells	89:127	Recombinant Chinese Hamster Ovary Cells	89:127	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	8	15	theme	ng/ml	1517:1521	arg1	EC50					1504:1507	EC50	1504:1507	EC50 of 2.93 ng/ml	1504:1521	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	4	16	theme	bioreactor	843:852	arg1	cultures					854:861	bioreactor cultures	843:861	bioreactor cultures	843:861	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	5	17	theme	7.5-L	950:954	arg1	bioreactor					956:965	the 7.5-L bioreactor	946:965	the 7.5-L bioreactor	946:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	1	18	theme	high	265:268	arg1	expression					270:279	the high expression	261:279	the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes	261:388	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	7	19	theme	N-terminal	1223:1232	arg1	sequences					1245:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	7	20	theme	purified	1289:1296	arg1	rhBMP-4					1298:1304	the purified rhBMP-4	1285:1304	the purified rhBMP-4	1285:1304	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	6	21	dep	%	1216:1216	arg1	95					1214:1215	95	1214:1215	95	1214:1215	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	6	22	theme	culture	1066:1072	arg1	supernatant					1074:1084	the culture supernatant	1062:1084	the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%	1062:1216	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	0	23	theme	Ovary	117:121	arg1	Cells					123:127	Recombinant Chinese Hamster Ovary Cells	89:127	Recombinant Chinese Hamster Ovary Cells	89:127	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	3	24	theme	recombinant	674:684	arg1	expression					692:701	recombinant furin expression	674:701	recombinant furin expression	674:701	The expression of the mature rhBMP-4 was significantly enhanced by recombinant furin expression.
28535613	2	25	theme	working	590:596	arg1	volume					598:603	working volume	590:603	5 L working volume	586:603	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	4	26	theme	medium	744:749	arg1	solution					777:784	a nutrient supplement solution	755:784	a nutrient supplement solution for high expression of rhBMP-4	755:815	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	4	26	theme	medium	744:749	arg1	combination					708:718	The combination	704:718	The combination of a chemically defined medium	704:749	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	8	27	theme	mature	1397:1402	arg1	active					1456:1461	active	1456:1461	active	1456:1461	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	8	27	theme	mature	1397:1402	arg1	rhBMP-4					1413:1419	The mature purified rhBMP-4	1393:1419	The mature purified rhBMP-4	1393:1419	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	2	28	dep	L	588:588	arg1	volume					598:603	working volume	590:603	5 L working volume	586:603	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	1	29	theme	therapeutic	369:379	arg1	purposes					381:388	therapeutic purposes	369:388	therapeutic purposes	369:388	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	5	30	theme	rhBMP-4-expressing	913:930	arg1	cells					937:941	the established rhBMP-4-expressing rCHO cells	897:941	the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor	897:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	7	31	theme	rhBMP-4	1298:1304	arg1	sequences					1245:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	7	31	theme	rhBMP-4	1298:1304	arg1	glycosylation					1268:1280	N-linked glycosylation	1259:1280	N-linked glycosylation of the purified rhBMP-4	1259:1304	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	5	32	from	cultures	885:892	arg1	bioreactor					956:965	the 7.5-L bioreactor	946:965	the 7.5-L bioreactor	946:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	5	33	theme	rCHO	932:935	arg1	cells					937:941	the established rhBMP-4-expressing rCHO cells	897:941	the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor	897:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	7	34	theme	de-N-glycosylation	1350:1367	arg1	analysis					1369:1376	de-N-glycosylation analysis	1350:1376	de-N-glycosylation analysis	1350:1376	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	1	35	theme	therapeutic	189:199	arg1	potential					201:209	therapeutic potential	189:209	therapeutic potential for various diseases, including cancers	189:249	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	2	36	theme	current	424:430	arg1	study					432:436	the current study	420:436	the current study	420:436	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	8	37	theme	purified	1404:1411	arg1	active					1456:1461	active	1456:1461	active	1456:1461	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	8	37	theme	purified	1404:1411	arg1	rhBMP-4					1413:1419	The mature purified rhBMP-4	1393:1419	The mature purified rhBMP-4	1393:1419	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	5	38	theme	cells	937:941	arg1	cultures					885:892	The 11-day fed-batch cultures	864:892	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor	864:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	5	39	theme	rhBMP-4	1001:1007	arg1	mg/l					993:996	approximately 32 mg/l	976:996	approximately 32 mg/l of rhBMP-4	976:1007	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	2	40	theme	recombinant	456:466	arg1	line					502:505	a recombinant Chinese hamster ovary (rCHO) cell line	454:505	a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume)	454:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	4	41	used	used	834:837	arg2	combination					708:718	The combination	704:718	The combination of a chemically defined medium	704:749	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	6	42	theme	%	1178:1178	arg1	purity					1194:1199	a protein purity	1184:1199	a protein purity greater than 95%	1184:1216	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	6	42	theme	%	1178:1178	arg1	rate					1154:1157	a recovery rate	1143:1157	a recovery rate of approximately 55%	1143:1178	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	6	43	theme	recovery	1145:1152	arg1	rate					1154:1157	a recovery rate	1143:1157	a recovery rate of approximately 55%	1143:1178	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	0	44	theme	Active	44:49	arg1	Protein-4					76:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	1	45	theme	active	297:302	arg1	rhBMP-4					329:335	rhBMP-4	329:335	rhBMP-4	329:335	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	45	theme	active	297:302	arg1	BMP-4					322:326	recombinant human BMP-4	304:326	biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes	284:388	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	46	contain	have	184:187	arg1	BMP-4					160:164	BMP-4	160:164	BMP-4	160:164	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	46	contain	have	184:187	arg1	protein-4					149:157	Bone morphogenetic protein-4	130:157	Bone morphogenetic protein-4 (BMP-4)	130:165	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	46	contain	have	184:187	arg2	potential					201:209	therapeutic potential	189:209	therapeutic potential for various diseases, including cancers	189:249	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	4	47	theme	high	790:793	arg1	expression					795:804	high expression	790:804	high expression of rhBMP-4	790:815	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	1	48	theme	various	215:221	arg1	cancers					243:249	cancers	243:249	cancers	243:249	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	48	theme	various	215:221	arg1	diseases					223:230	various diseases	215:230	various diseases	215:230	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	49	theme	recombinant	304:314	arg1	rhBMP-4					329:335	rhBMP-4	329:335	rhBMP-4	329:335	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	49	theme	recombinant	304:314	arg1	BMP-4					322:326	recombinant human BMP-4	304:326	biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes	284:388	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	2	50	theme	rCHO	491:494	arg1	line					502:505	a recombinant Chinese hamster ovary (rCHO) cell line	454:505	a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume)	454:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	0	51	theme	Bone	57:60	arg1	Protein-4					76:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	1	52	theme	human	316:320	arg1	rhBMP-4					329:335	rhBMP-4	329:335	rhBMP-4	329:335	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	52	theme	human	316:320	arg1	BMP-4					322:326	recombinant human BMP-4	304:326	biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes	284:388	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	2	53	theme	ovary	484:488	arg1	line					502:505	a recombinant Chinese hamster ovary (rCHO) cell line	454:505	a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume)	454:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	0	54	theme	Human	51:55	arg1	Protein-4					76:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	1	55	theme	BMP-4	322:326	arg1	expression					270:279	the high expression	261:279	the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes	261:388	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	2	56	theme	production	543:552	arg1	process					554:560	a production process	541:560	rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume)	522:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	3	57	theme	mature	629:634	arg1	rhBMP-4					636:642	the mature rhBMP-4	625:642	the mature rhBMP-4	625:642	The expression of the mature rhBMP-4 was significantly enhanced by recombinant furin expression.
28535613	4	58	theme	rhBMP-4	809:815	arg1	expression					795:804	high expression	790:804	high expression of rhBMP-4	790:815	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	1	59	theme	Bone	130:133	arg1	BMP-4					160:164	BMP-4	160:164	BMP-4	160:164	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	59	theme	Bone	130:133	arg1	protein-4					149:157	Bone morphogenetic protein-4	130:157	Bone morphogenetic protein-4 (BMP-4)	130:165	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	5	60	from	cells	937:941	arg1	bioreactor					956:965	the 7.5-L bioreactor	946:965	the 7.5-L bioreactor	946:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	3	61	theme	rhBMP-4	636:642	arg1	expression					611:620	The expression	607:620	The expression of the mature rhBMP-4	607:642	The expression of the mature rhBMP-4 was significantly enhanced by recombinant furin expression.
28535613	4	62	theme	nutrient	757:764	arg1	solution					777:784	a nutrient supplement solution	755:784	a nutrient supplement solution for high expression of rhBMP-4	755:815	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	1	63	theme	morphogenetic	135:147	arg1	BMP-4					160:164	BMP-4	160:164	BMP-4	160:164	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	1	63	theme	morphogenetic	135:147	arg1	protein-4					149:157	Bone morphogenetic protein-4	130:157	Bone morphogenetic protein-4 (BMP-4)	130:165	Bone morphogenetic protein-4 (BMP-4) is considered to have therapeutic potential for various diseases, including cancers; however, the high expression of biologically active recombinant human BMP-4 (rhBMP-4) needed for its manufacture for therapeutic purposes has yet to be established.
28535613	6	64	theme	chromatographic	1103:1117	arg1	procedure					1119:1127	a two-step chromatographic procedure	1092:1127	a two-step chromatographic procedure	1092:1127	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	6	65	theme	mature	1014:1019	arg1	rhBMP-4					1021:1027	The mature rhBMP-4	1010:1027	The mature rhBMP-4	1010:1027	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	7	66	link	N-linked	1259:1266	arg1	glycosylation					1268:1280	N-linked glycosylation	1259:1280	N-linked glycosylation of the purified rhBMP-4	1259:1304	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	7	67	theme	N-linked	1259:1266	arg1	glycosylation					1268:1280	N-linked glycosylation	1259:1280	N-linked glycosylation of the purified rhBMP-4	1259:1304	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	6	68	theme	protein	1186:1192	arg1	purity					1194:1199	a protein purity	1184:1199	a protein purity greater than 95%	1184:1216	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	5	69	theme	established	901:911	arg1	cells					937:941	the established rhBMP-4-expressing rCHO cells	897:941	the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor	897:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	6	70	dep	purity	1194:1199	arg1	%					1216:1216	%	1216:1216	%	1216:1216	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	0	71	theme	Protein-4	76:84	arg1	Purification					15:26	Purification	15:26	Purification	15:26	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	0	71	theme	Protein-4	76:84	arg1	Expression					0:9	Expression	0:9	Expression	0:9	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	8	72	theme	effective	1472:1480	arg1	concentration					1487:1499	an effective dose concentration	1469:1499	an effective dose concentration of EC50 of 2.93 ng/ml	1469:1521	The mature purified rhBMP-4 has been proved to be functionally active, with an effective dose concentration of EC50 of 2.93 ng/ml.
28535613	7	73	theme	N-terminal	1324:1333	arg1	sequencing					1335:1344	N-terminal sequencing	1324:1344	N-terminal sequencing	1324:1344	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	6	74	theme	two-step	1094:1101	arg1	procedure					1119:1127	a two-step chromatographic procedure	1092:1127	a two-step chromatographic procedure	1092:1127	The mature rhBMP-4 was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure, resulting in a recovery rate of approximately 55% and a protein purity greater than 95%.
28535613	0	75	theme	Morphogenetic	62:74	arg1	Protein-4					76:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Biologically Active Human Bone Morphogenetic Protein-4	31:84	Expression and Purification of Biologically Active Human Bone Morphogenetic Protein-4 in Recombinant Chinese Hamster Ovary Cells.
28535613	2	76	dep	bioreactor	574:583	arg1	L					588:588	5 L	586:588	5 L working volume	586:603	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28535613	4	77	theme	supplement	766:775	arg1	solution					777:784	a nutrient supplement solution	755:784	a nutrient supplement solution for high expression of rhBMP-4	755:815	The combination of a chemically defined medium and a nutrient supplement solution for high expression of rhBMP-4 was selected and used for bioreactor cultures.
28535613	7	78	theme	acid	1240:1243	arg1	sequences					1245:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	7	79	theme	amino	1234:1238	arg1	sequences					1245:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences	1219:1253	The N-terminal amino acid sequences and N-linked glycosylation of the purified rhBMP-4 were confirmed by N-terminal sequencing and de-N-glycosylation analysis, respectively.
28535613	5	80	from	bioreactor	956:965	arg1	cultures					885:892	The 11-day fed-batch cultures	864:892	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor	864:965	The 11-day fed-batch cultures of the established rhBMP-4-expressing rCHO cells in the 7.5-L bioreactor produced approximately 32 mg/l of rhBMP-4.
28535613	2	81	theme	cell	497:500	arg1	line					502:505	a recombinant Chinese hamster ovary (rCHO) cell line	454:505	a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume)	454:604	In the current study, we established a recombinant Chinese hamster ovary (rCHO) cell line overexpressing rhBMP-4 as well as a production process using 7.5-l bioreactor (5 L working volume).
28528272	7	0	from	Legumain	1057:1064	arg1	cells					1085:1089	whole cells	1079:1089	whole cells	1079:1089	Legumain and probe in whole cells were studied by immunofluorescence.
28528272	2	1	theme	proteins	348:355	arg1	functions					329:337	the functions	325:337	the functions of these proteins	325:355	However, little is known about the nature of the carbohydrate groups and whether they affect the functions of these proteins.
28528272	6	2	theme	activity-based	903:916	arg1	probe					918:922	legumain selective activity-based probe	884:922	legumain selective activity-based probe	884:922	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	7	3	from	probe	1070:1074	arg1	cells					1085:1089	whole cells	1079:1089	whole cells	1079:1089	Legumain and probe in whole cells were studied by immunofluorescence.
28528272	2	4	theme	carbohydrate	281:292	arg1	groups					294:299	the carbohydrate groups	277:299	the carbohydrate groups	277:299	However, little is known about the nature of the carbohydrate groups and whether they affect the functions of these proteins.
28528272	9	5	theme	unglycosylated	1438:1451	arg1	prolegumain					1453:1463	unglycosylated prolegumain	1438:1463	unglycosylated prolegumain	1438:1463	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	6	6	theme	legumain	884:891	arg1	probe					918:922	legumain selective activity-based probe	884:922	legumain selective activity-based probe	884:922	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	13	7	theme	similar	1970:1976	arg1	capacity					1978:1985	similar capacity to inhibit legumain	1970:2005	similar capacity to inhibit legumain	1970:2005	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	1	8	theme	inhibitor	178:186	arg1	E/M					197:199	its inhibitor cystatin E/M	174:199	its inhibitor cystatin E/M	174:199	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M are endogenously glycosylated.
28528272	1	9	gly	glycosylated	218:229	arg1	endopeptidase					147:159	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M	131:199	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M	131:199	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M are endogenously glycosylated.
28528272	8	10	theme	high	1191:1194	arg1	type					1204:1207	high mannose type	1191:1207	high mannose type	1191:1207	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	12	11	theme	mature	1782:1787	arg1	legumain					1789:1796	mature legumain	1782:1796	mature legumain (36 kDa)	1782:1805	Also, internalization of mature legumain (36 kDa) was visualized both alone and complexed with probe.
28528272	12	11	theme	mature	1782:1787	arg1	kDa					1802:1804	36 kDa	1799:1804	36 kDa	1799:1804	Also, internalization of mature legumain (36 kDa) was visualized both alone and complexed with probe.
28528272	8	12	theme	complex	1252:1258	arg1	mannose-linked					1260:1273	complex mannose-linked	1252:1273	complex mannose-linked	1252:1273	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	8	12	theme	complex	1252:1258	arg1	E/M					1227:1229	cystatin E/M	1218:1229	cystatin E/M	1218:1229	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	0	13	theme	inhibitory	109:118	arg1	functions					120:128	cystatin E/M inhibitory functions	96:128	cystatin E/M inhibitory functions	96:128	Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions.
28528272	14	14	theme	glycosylation	2195:2207	arg1	status					2209:2214	the glycosylation status	2191:2214	the glycosylation status	2191:2214	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	14	15	gly	glycosylation	2023:2035	arg1	prolegumain					2040:2050	prolegumain	2040:2050	prolegumain	2040:2050	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	12	16	dep	visualized	1811:1820	arg1	both					1822:1825	both	1822:1825	both	1822:1825	Also, internalization of mature legumain (36 kDa) was visualized both alone and complexed with probe.
28528272	12	16	dep	visualized	1811:1820	arg1	complexed					1837:1845	complexed	1837:1845	complexed with probe	1837:1856	Also, internalization of mature legumain (36 kDa) was visualized both alone and complexed with probe.
28528272	6	17	theme	cystatin	945:952	arg1	E/M					954:956	cystatin E/M	945:956	cystatin E/M	945:956	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	4	18	theme	HEK293	458:463	arg1	cells					536:540	HCT116 cells	529:540	HCT116 cells	529:540	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	18	theme	HEK293	458:463	arg1	lines					470:474	HEK293 cell lines	458:474	HEK293 cell lines stably over-expressing legumain or cystatin E/M	458:522	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	18	theme	HEK293	458:463	arg1	models					560:565	cell models	555:565	cell models	555:565	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	9	19	gly	glycosylated	1282:1293	arg1	prolegumain					1295:1305	glycosylated prolegumain	1282:1305	glycosylated prolegumain	1282:1305	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	14	20	from	conclusion	2011:2020	arg1	necessary					2055:2063	necessary	2055:2063	necessary	2055:2063	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	13	21	theme	cystatin	1950:1957	arg1	E/M					1959:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	6	22	theme	cell	1022:1025	arg1	lysates					1027:1033	cell lysates	1022:1033	cell lysates	1022:1033	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	5	23	theme	Endo	755:758	arg1	H					760:760	Endo H	755:760	Endo H	755:760	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	13	24	gly	unglycosylated	1935:1948	arg1	E/M					1959:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	14	25	from	necessary	2055:2063	arg1	conclusion					2011:2020	conclusion	2011:2020	conclusion	2011:2020	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	14	26	theme	E/M	2169:2171	arg1	property					2148:2155	the inhibitory property	2133:2155	the inhibitory property of cystatin E/M	2133:2171	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	14	26	theme	E/M	2169:2171	arg1	independent					2176:2186	independent	2176:2186	independent	2176:2186	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	9	27	gly	unglycosylated	1337:1350	arg1	form					1352:1355	the unglycosylated form	1333:1355	the unglycosylated form	1333:1355	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	5	28	theme	glycosylation	719:731	arg1	tunicamycin					681:691	tunicamycin	681:691	tunicamycin	681:691	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	5	28	theme	glycosylation	719:731	arg1	inhibitor					697:705	an inhibitor	694:705	an inhibitor of N-linked glycosylation	694:731	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	3	29	gly	unglycosylated	394:407	arg1	E/M					440:442	cystatin E/M	431:442	cystatin E/M	431:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	3	29	gly	unglycosylated	394:407	arg1	forms					409:413	both glycosylated and unglycosylated forms	372:413	both glycosylated and unglycosylated forms of legumain and cystatin E/M	372:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	3	29	gly	unglycosylated	394:407	arg1	legumain					418:425	legumain	418:425	legumain	418:425	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	12	30	dep	both	1822:1825	arg1	alone					1827:1831	alone	1827:1831	alone	1827:1831	Also, internalization of mature legumain (36 kDa) was visualized both alone and complexed with probe.
28528272	3	31	theme	E/M	440:442	arg1	forms					409:413	both glycosylated and unglycosylated forms	372:413	both glycosylated and unglycosylated forms of legumain and cystatin E/M	372:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	0	32	theme	cystatin	96:103	arg1	functions					120:128	cystatin E/M inhibitory functions	96:128	cystatin E/M inhibitory functions	96:128	Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions.
28528272	3	33	gly	glycosylated	377:388	arg1	E/M					440:442	cystatin E/M	431:442	cystatin E/M	431:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	3	33	gly	glycosylated	377:388	arg1	forms					409:413	both glycosylated and unglycosylated forms	372:413	both glycosylated and unglycosylated forms of legumain and cystatin E/M	372:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	3	33	gly	glycosylated	377:388	arg1	legumain					418:425	legumain	418:425	legumain	418:425	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	3	34	theme	glycosylated	377:388	arg1	forms					409:413	both glycosylated and unglycosylated forms	372:413	both glycosylated and unglycosylated forms of legumain and cystatin E/M	372:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	14	35	theme	inhibitory	2137:2146	arg1	property					2148:2155	the inhibitory property	2133:2155	the inhibitory property of cystatin E/M	2133:2171	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	14	35	theme	inhibitory	2137:2146	arg1	independent					2176:2186	independent	2176:2186	independent	2176:2186	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	0	36	theme	active	71:76	arg1	forms					78:82	active forms	71:82	active forms	71:82	Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions.
28528272	13	37	theme	glycosylation	1898:1910	arg1	importance					1875:1884	the importance	1871:1884	the importance of legumain glycosylation	1871:1910	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	13	38	gly	glycosylated	1918:1929	arg1	E/M					1959:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	10	39	theme	active	1536:1541	arg1	form					1543:1546	the mature active form	1525:1546	the mature active form	1525:1546	Glycosylated prolegumain was internalized and processed to the mature active form, but no internalization of unglycosylated prolegumain was observed.
28528272	5	40	used	used	767:770	arg2	H					760:760	Endo H	755:760	Endo H	755:760	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	5	40	used	used	767:770	arg2	F					749:749	PNGase F	742:749	PNGase F	742:749	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	4	41	theme	cell	555:558	arg1	cells					536:540	HCT116 cells	529:540	HCT116 cells	529:540	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	41	theme	cell	555:558	arg1	lines					470:474	HEK293 cell lines	458:474	HEK293 cell lines stably over-expressing legumain or cystatin E/M	458:522	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	41	theme	cell	555:558	arg1	models					560:565	cell models	555:565	cell models	555:565	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	11	42	theme	intracellular	1733:1745	arg1	legumain					1747:1754	intracellular legumain	1733:1754	intracellular legumain	1733:1754	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	6	43	gly	glycosylated	839:850	arg1	proteins					868:875	glycosylated, unglycosylated proteins	839:875	glycosylated, unglycosylated proteins	839:875	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	0	44	theme	legumain	31:38	arg1	localization					40:51	legumain localization	31:51	legumain localization	31:51	Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions.
28528272	6	45	theme	glycosylated	839:850	arg1	proteins					868:875	glycosylated, unglycosylated proteins	839:875	glycosylated, unglycosylated proteins	839:875	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	3	46	theme	unglycosylated	394:407	arg1	forms					409:413	both glycosylated and unglycosylated forms	372:413	both glycosylated and unglycosylated forms of legumain and cystatin E/M	372:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	4	47	theme	HCT116	529:534	arg1	cells					536:540	HCT116 cells	529:540	HCT116 cells	529:540	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	47	theme	HCT116	529:534	arg1	lines					470:474	HEK293 cell lines	458:474	HEK293 cell lines stably over-expressing legumain or cystatin E/M	458:522	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	47	theme	HCT116	529:534	arg1	models					560:565	cell models	555:565	cell models	555:565	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	11	48	theme	activity-based	1649:1662	arg1	tool					1719:1722	a novel tool	1711:1722	a novel tool to study intracellular legumain	1711:1754	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	48	theme	activity-based	1649:1662	arg1	MP-L09					1671:1676	MP-L09	1671:1676	MP-L09	1671:1676	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	48	theme	activity-based	1649:1662	arg1	probe					1664:1668	A Cy5-labelled legumain specific activity-based probe	1616:1668	A Cy5-labelled legumain specific activity-based probe (MP-L09)	1616:1677	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	49	theme	legumain	1631:1638	arg1	tool					1719:1722	a novel tool	1711:1722	a novel tool to study intracellular legumain	1711:1754	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	49	theme	legumain	1631:1638	arg1	MP-L09					1671:1676	MP-L09	1671:1676	MP-L09	1671:1676	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	49	theme	legumain	1631:1638	arg1	probe					1664:1668	A Cy5-labelled legumain specific activity-based probe	1616:1668	A Cy5-labelled legumain specific activity-based probe (MP-L09)	1616:1677	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	10	50	theme	prolegumain	1590:1600	arg1	internalization					1556:1570	no internalization	1553:1570	no internalization of unglycosylated prolegumain	1553:1600	Glycosylated prolegumain was internalized and processed to the mature active form, but no internalization of unglycosylated prolegumain was observed.
28528272	9	51	gly	unglycosylated	1438:1451	arg1	prolegumain					1453:1463	unglycosylated prolegumain	1438:1463	unglycosylated prolegumain	1438:1463	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	5	52	gly	unglycosylated	632:645	arg1	proteins					647:654	unglycosylated proteins	632:654	unglycosylated proteins	632:654	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	5	53	theme	unglycosylated	632:645	arg1	proteins					647:654	unglycosylated proteins	632:654	unglycosylated proteins	632:654	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	4	54	used	used	547:550	arg2	models					560:565	cell models	555:565	cell models	555:565	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	54	used	used	547:550	arg2	lines					470:474	HEK293 cell lines	458:474	HEK293 cell lines stably over-expressing legumain or cystatin E/M	458:522	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	54	used	used	547:550	arg2	cells					536:540	HCT116 cells	529:540	HCT116 cells	529:540	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	2	55	theme	groups	294:299	arg1	nature					267:272	the nature	263:272	the nature of the carbohydrate groups	263:299	However, little is known about the nature of the carbohydrate groups and whether they affect the functions of these proteins.
28528272	6	56	theme	selective	893:901	arg1	probe					918:922	legumain selective activity-based probe	884:922	legumain selective activity-based probe	884:922	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	4	57	theme	mature	572:577	arg1	legumain					579:586	mature legumain	572:586	mature legumain	572:586	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	11	58	theme	novel	1713:1717	arg1	tool					1719:1722	a novel tool	1711:1722	a novel tool to study intracellular legumain	1711:1754	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	58	theme	novel	1713:1717	arg1	probe					1664:1668	A Cy5-labelled legumain specific activity-based probe	1616:1668	A Cy5-labelled legumain specific activity-based probe (MP-L09)	1616:1677	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	5	59	link	N-linked	710:717	arg1	glycosylation					719:731	N-linked glycosylation	710:731	N-linked glycosylation	710:731	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	9	60	theme	prolegumain	1453:1463	arg1	autoactivation					1420:1433	autoactivation	1420:1433	autoactivation of unglycosylated prolegumain	1420:1463	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	8	61	theme	cystatin	1218:1225	arg1	mannose-linked					1260:1273	complex mannose-linked	1252:1273	complex mannose-linked	1252:1273	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	8	61	theme	cystatin	1218:1225	arg1	E/M					1227:1229	cystatin E/M	1218:1229	cystatin E/M	1218:1229	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	7	62	theme	whole	1079:1083	arg1	cells					1085:1089	whole cells	1079:1089	whole cells	1079:1089	Legumain and probe in whole cells were studied by immunofluorescence.
28528272	1	63	theme	cystatin	188:195	arg1	E/M					197:199	its inhibitor cystatin E/M	174:199	its inhibitor cystatin E/M	174:199	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M are endogenously glycosylated.
28528272	6	64	theme	activity	973:980	arg1	measurement					982:992	activity measurement	973:992	activity measurement	973:992	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	12	65	theme	legumain	1789:1796	arg1	internalization					1763:1777	internalization	1763:1777	internalization of mature legumain (36 kDa)	1763:1805	Also, internalization of mature legumain (36 kDa) was visualized both alone and complexed with probe.
28528272	14	66	theme	status	2209:2214	arg1	property					2148:2155	the inhibitory property	2133:2155	the inhibitory property of cystatin E/M	2133:2171	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	14	66	theme	status	2209:2214	arg1	independent					2176:2186	independent	2176:2186	independent	2176:2186	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	8	67	theme	mannose	1196:1202	arg1	type					1204:1207	high mannose type	1191:1207	high mannose type	1191:1207	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	4	68	theme	cell	465:468	arg1	cells					536:540	HCT116 cells	529:540	HCT116 cells	529:540	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	68	theme	cell	465:468	arg1	lines					470:474	HEK293 cell lines	458:474	HEK293 cell lines stably over-expressing legumain or cystatin E/M	458:522	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	4	68	theme	cell	465:468	arg1	models					560:565	cell models	555:565	cell models	555:565	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	13	69	theme	unglycosylated	1935:1948	arg1	E/M					1959:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	10	70	gly	unglycosylated	1575:1588	arg1	prolegumain					1590:1600	unglycosylated prolegumain	1575:1600	unglycosylated prolegumain	1575:1600	Glycosylated prolegumain was internalized and processed to the mature active form, but no internalization of unglycosylated prolegumain was observed.
28528272	5	71	theme	PNGase	742:747	arg1	F					749:749	PNGase F	742:749	PNGase F	742:749	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	1	72	theme	asparaginyl	135:145	arg1	endopeptidase					147:159	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M	131:199	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M	131:199	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M are endogenously glycosylated.
28528272	4	73	theme	cystatin	511:518	arg1	E/M					520:522	cystatin E/M	511:522	cystatin E/M	511:522	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	9	74	theme	glycosylated	1282:1293	arg1	prolegumain					1295:1305	glycosylated prolegumain	1282:1305	glycosylated prolegumain	1282:1305	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	10	75	theme	Glycosylated	1466:1477	arg1	prolegumain					1479:1489	Glycosylated prolegumain	1466:1489	Glycosylated prolegumain	1466:1489	Glycosylated prolegumain was internalized and processed to the mature active form, but no internalization of unglycosylated prolegumain was observed.
28528272	14	76	theme	cystatin	2160:2167	arg1	E/M					2169:2171	cystatin E/M	2160:2171	cystatin E/M	2160:2171	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	13	77	theme	glycosylated	1918:1929	arg1	E/M					1959:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	both glycosylated and unglycosylated cystatin E/M	1913:1961	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	5	78	theme	N-linked	710:717	arg1	glycosylation					719:731	N-linked glycosylation	710:731	N-linked glycosylation	710:731	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	14	79	theme	correct	2069:2075	arg1	processing					2077:2086	correct processing	2069:2086	correct processing to active forms and internalization	2069:2122	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	8	80	dep	shown	1162:1166	arg1	whereas					1210:1216	whereas	1210:1216	whereas	1210:1216	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	0	81	theme	E/M	105:107	arg1	functions					120:128	cystatin E/M inhibitory functions	96:128	cystatin E/M inhibitory functions	96:128	Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions.
28528272	5	82	dep	treated	668:674	arg1	whereas					734:740	whereas	734:740	whereas	734:740	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	13	83	theme	legumain	1889:1896	arg1	glycosylation					1898:1910	legumain glycosylation	1889:1910	legumain glycosylation	1889:1910	Contrary to the importance of legumain glycosylation, both glycosylated and unglycosylated cystatin E/M showed similar capacity to inhibit legumain.
28528272	14	84	theme	prolegumain	2040:2050	arg1	glycosylation					2023:2035	glycosylation	2023:2035	glycosylation of prolegumain	2023:2050	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	3	85	theme	cystatin	431:438	arg1	E/M					440:442	cystatin E/M	431:442	cystatin E/M	431:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	5	86	theme	glycosylation	792:804	arg1	types					806:810	the glycosylation types	788:810	the glycosylation types	788:810	To obtain unglycosylated proteins, cells were treated with tunicamycin, an inhibitor of N-linked glycosylation, whereas PNGase F and Endo H were used to characterize the glycosylation types.
28528272	9	87	theme	unglycosylated	1337:1350	arg1	form					1352:1355	the unglycosylated form	1333:1355	the unglycosylated form	1333:1355	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	10	88	theme	mature	1529:1534	arg1	form					1543:1546	the mature active form	1525:1546	the mature active form	1525:1546	Glycosylated prolegumain was internalized and processed to the mature active form, but no internalization of unglycosylated prolegumain was observed.
28528272	1	89	dep	endopeptidase	147:159	arg1	E/M					197:199	its inhibitor cystatin E/M	174:199	its inhibitor cystatin E/M	174:199	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M are endogenously glycosylated.
28528272	1	89	dep	endopeptidase	147:159	arg1	legumain					161:168	legumain	161:168	legumain	161:168	The asparaginyl endopeptidase legumain and its inhibitor cystatin E/M are endogenously glycosylated.
28528272	4	90	dep	lines	470:474	arg1	over-expressing					483:497	over-expressing	483:497	over-expressing	483:497	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	6	91	theme	conditioned	1038:1048	arg1	media					1050:1054	conditioned media	1038:1054	conditioned media	1038:1054	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	3	92	theme	legumain	418:425	arg1	forms					409:413	both glycosylated and unglycosylated forms	372:413	both glycosylated and unglycosylated forms of legumain and cystatin E/M	372:442	In this study both glycosylated and unglycosylated forms of legumain and cystatin E/M were studied.
28528272	6	93	dep	glycosylated	839:850	arg1	unglycosylated					853:866	unglycosylated	853:866	unglycosylated	853:866	Cells were incubated with glycosylated, unglycosylated proteins and/or legumain selective activity-based probe, and legumain and/or cystatin E/M was studied by activity measurement, ELISA or immunoblotting in cell lysates or conditioned media.
28528272	11	94	theme	specific	1640:1647	arg1	tool					1719:1722	a novel tool	1711:1722	a novel tool to study intracellular legumain	1711:1754	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	94	theme	specific	1640:1647	arg1	MP-L09					1671:1676	MP-L09	1671:1676	MP-L09	1671:1676	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	94	theme	specific	1640:1647	arg1	probe					1664:1668	A Cy5-labelled legumain specific activity-based probe	1616:1668	A Cy5-labelled legumain specific activity-based probe (MP-L09)	1616:1677	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	8	95	from	carbohydrates	1131:1143	arg1	legumain					1148:1155	legumain	1148:1155	legumain	1148:1155	The carbohydrates on legumain were shown to be of the hybrid or high mannose type, whereas cystatin E/M was characterized as complex mannose-linked.
28528272	14	96	theme	active	2091:2096	arg1	forms					2098:2102	active forms	2091:2102	active forms	2091:2102	In conclusion, glycosylation of prolegumain is necessary for correct processing to active forms and internalization, whereas the inhibitory property of cystatin E/M is independent of the glycosylation status.
28528272	11	97	theme	Cy5-labelled	1618:1629	arg1	tool					1719:1722	a novel tool	1711:1722	a novel tool to study intracellular legumain	1711:1754	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	97	theme	Cy5-labelled	1618:1629	arg1	MP-L09					1671:1676	MP-L09	1671:1676	MP-L09	1671:1676	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	11	97	theme	Cy5-labelled	1618:1629	arg1	probe					1664:1668	A Cy5-labelled legumain specific activity-based probe	1616:1668	A Cy5-labelled legumain specific activity-based probe (MP-L09)	1616:1677	A Cy5-labelled legumain specific activity-based probe (MP-L09) was synthesized and shown to be a novel tool to study intracellular legumain.
28528272	9	98	theme	glycosaminoglycans	1382:1399	arg1	addition					1370:1377	addition	1370:1377	addition of glycosaminoglycans	1370:1399	While glycosylated prolegumain was able to autoactivate, the unglycosylated form was not, and addition of glycosaminoglycans did not facilitate autoactivation of unglycosylated prolegumain.
28528272	4	99	theme	bovine	606:611	arg1	kidneys					613:619	bovine kidneys	606:619	bovine kidneys	606:619	HEK293 cell lines stably over-expressing legumain or cystatin E/M, and HCT116 cells were used as cell models, and mature legumain was purified from bovine kidneys.
28528272	10	100	theme	unglycosylated	1575:1588	arg1	prolegumain					1590:1600	unglycosylated prolegumain	1575:1600	unglycosylated prolegumain	1575:1600	Glycosylated prolegumain was internalized and processed to the mature active form, but no internalization of unglycosylated prolegumain was observed.
28368034	0	0	theme	Secretory	76:84	arg1	IgA					86:88	Plant-based Recombinant Secretory IgA	52:88	Plant-based Recombinant Secretory IgA	52:88	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	4	1	theme	recombinant	585:595	arg1	S-hyIgA					602:608	S-hyIgA	602:608	S-hyIgA	602:608	Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant.
28368034	4	1	theme	recombinant	585:595	arg1	IgA					597:599	the recombinant IgA	581:599	the recombinant IgA (S-hyIgA)	581:609	Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant.
28368034	1	2	theme	food-poisoning	134:147	arg1	factor					124:129	a major virulence factor	106:129	a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7	106:190	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	1	2	theme	food-poisoning	134:147	arg1	toxin					97:101	Shiga toxin	91:101	Shiga toxin	91:101	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	0	3	theme	Recombinant	64:74	arg1	IgA					86:88	Plant-based Recombinant Secretory IgA	52:88	Plant-based Recombinant Secretory IgA	52:88	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	7	4	theme	Ig	985:986	arg1	chain					994:998	Ig heavy chain	985:998	Ig heavy chain	985:998	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	3	5	theme	IgG	447:449	arg1	mAb					451:453	a mouse IgG mAb	439:453	a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	439:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	8	6	theme	carcinoma	1268:1276	arg1	line					1283:1286	human colon carcinoma cell line	1256:1286	a human colon carcinoma cell line	1254:1286	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	8	6	theme	carcinoma	1268:1276	arg1	cells					1247:1251	butyrate-treated Caco-2 cells	1223:1251	butyrate-treated Caco-2 cells	1223:1251	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	7	7	theme	heavy	988:992	arg1	chain					994:998	Ig heavy chain	985:998	Ig heavy chain	985:998	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	6	8	theme	sugar	967:971	arg1	chains					973:978	plant-specific N-linked sugar chains	943:978	plant-specific N-linked sugar chains	943:978	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	0	9	from	Protection	0:9	arg1	Toxin					43:47	Shiga Toxin	37:47	Shiga Toxin	37:47	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	3	10	theme	binding	472:478	arg1	subunit					480:486	the binding subunit	468:486	the binding subunit of Shiga toxin 1 (Stx1)	468:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	4	11	theme	Arabidopsis	627:637	arg1	plant					648:652	transgenic Arabidopsis thaliana plant	616:652	transgenic Arabidopsis thaliana plant	616:652	Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant.
28368034	4	12	theme	transgenic	616:625	arg1	plant					648:652	transgenic Arabidopsis thaliana plant	616:652	transgenic Arabidopsis thaliana plant	616:652	Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant.
28368034	0	13	from	Toxin	43:47	arg1	Protection					0:9	Protection	0:9	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.	0:89	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	0	13	from	Toxin	43:47	arg1	Cells					26:30	Human Colon Cells	14:30	Human Colon Cells from Shiga Toxin	14:47	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	5	14	theme	thaliana	829:836	arg1	protein					815:821	a chlorophyll a/b-binding protein	789:821	a chlorophyll a/b-binding protein of A. thaliana	789:836	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	3	15	from	mAb	451:453	arg1	regions					426:432	variable regions	417:432	variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	417:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	3	16	theme	mouse	441:445	arg1	mAb					451:453	a mouse IgG mAb	439:453	a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	439:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	8	17	theme	butyrate-treated	1223:1238	arg1	line					1283:1286	human colon carcinoma cell line	1256:1286	a human colon carcinoma cell line	1254:1286	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	8	17	theme	butyrate-treated	1223:1238	arg1	cells					1247:1251	butyrate-treated Caco-2 cells	1223:1251	butyrate-treated Caco-2 cells	1223:1251	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	7	18	theme	protein	1059:1065	arg1	structure					1077:1085	an intracellular protein body-like structure	1042:1085	an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy	1042:1140	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	3	19	theme	recombinant	365:375	arg1	antibody					388:395	a recombinant monoclonal antibody	363:395	a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	363:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	3	19	theme	recombinant	365:375	arg1	mAb					398:400	mAb	398:400	mAb	398:400	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	6	20	theme	plant-specific	943:956	arg1	chains					973:978	plant-specific N-linked sugar chains	943:978	plant-specific N-linked sugar chains	943:978	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	4	21	dep	Arabidopsis	627:637	arg1	thaliana					639:646	thaliana	639:646	thaliana	639:646	Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant.
28368034	5	22	theme	chlorophyll	791:801	arg1	protein					815:821	a chlorophyll a/b-binding protein	789:821	a chlorophyll a/b-binding protein of A. thaliana	789:836	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	6	23	theme	N-linked	958:965	arg1	chains					973:978	plant-specific N-linked sugar chains	943:978	plant-specific N-linked sugar chains	943:978	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	5	24	theme	viral	854:858	arg1	promoter					860:867	a viral promoter	852:867	a viral promoter	852:867	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	3	25	theme	specific	455:462	arg1	mAb					451:453	a mouse IgG mAb	439:453	a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	439:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	7	26	theme	transgenic	1094:1103	arg1	structure					1077:1085	an intracellular protein body-like structure	1042:1085	an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy	1042:1140	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	3	27	theme	toxin	497:501	arg1	subunit					480:486	the binding subunit	468:486	the binding subunit of Shiga toxin 1 (Stx1)	468:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	2	28	theme	oral	317:320	arg1	immunotherapy					322:334	oral immunotherapy	317:334	oral immunotherapy	317:334	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	7	29	theme	intracellular	1045:1057	arg1	structure					1077:1085	an intracellular protein body-like structure	1042:1085	an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy	1042:1140	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	5	30	dep	cDNAs	671:675	arg1	component					714:722	J chain and secretory component	692:722	component	714:722	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	5	30	dep	cDNAs	671:675	arg1	light					685:689	light	685:689	light	685:689	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	5	30	dep	cDNAs	671:675	arg1	chain					694:698	J chain and secretory component	692:722	chain	694:698	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	5	30	dep	cDNAs	671:675	arg1	heavy					678:682	heavy	678:682	heavy	678:682	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	5	31	theme	a/b-binding	803:813	arg1	protein					815:821	a chlorophyll a/b-binding protein	789:821	a chlorophyll a/b-binding protein of A. thaliana	789:836	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	3	32	theme	monoclonal	377:386	arg1	antibody					388:395	a recombinant monoclonal antibody	363:395	a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	363:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	3	32	theme	monoclonal	377:386	arg1	mAb					398:400	mAb	398:400	mAb	398:400	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	0	33	theme	Colon	20:24	arg1	Cells					26:30	Human Colon Cells	14:30	Human Colon Cells from Shiga Toxin	14:47	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	7	34	located	observed	1030:1037	arg1	structure					1077:1085	an intracellular protein body-like structure	1042:1085	an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy	1042:1140	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	7	34	located	observed	1030:1037	arg2	chain					994:998	Ig heavy chain	985:998	Ig heavy chain	985:998	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	7	34	located	observed	1030:1037	arg2	components					1014:1023	secretory components	1004:1023	secretory components	1004:1023	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	1	35	theme	Shiga	91:95	arg1	factor					124:129	a major virulence factor	106:129	a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7	106:190	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	1	35	theme	Shiga	91:95	arg1	toxin					97:101	Shiga toxin	91:101	Shiga toxin	91:101	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	9	36	theme	antibodies	1360:1369	arg1	development					1326:1336	the development	1322:1336	the development of edible therapeutic antibodies such as those for the treatment of mucosal infection	1322:1422	These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection.
28368034	0	37	theme	Human	14:18	arg1	Cells					26:30	Human Colon Cells	14:30	Human Colon Cells from Shiga Toxin	14:47	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	7	38	dep	transgenic	1094:1103	arg1	leaves					1105:1110	leaves	1105:1110	leaves on immuno-electron microscopy	1105:1140	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	3	39	theme	Shiga	491:495	arg1	toxin					497:501	Shiga toxin 1	491:503	Shiga toxin 1 (Stx1)	491:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	3	39	theme	Shiga	491:495	arg1	Stx1					506:509	Stx1	506:509	Stx1	506:509	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	9	40	theme	mucosal	1406:1412	arg1	infection					1414:1422	mucosal infection	1406:1422	mucosal infection	1406:1422	These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection.
28368034	5	41	theme	S-hyIgA	663:669	arg1	cDNAs					671:675	All the S-hyIgA cDNAs	655:675	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component)	655:723	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	4	42	theme	IgA	597:599	arg1	form					573:576	a secretory form	561:576	a secretory form of the recombinant IgA (S-hyIgA)	561:609	Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant.
28368034	7	43	theme	body-like	1067:1075	arg1	structure					1077:1085	an intracellular protein body-like structure	1042:1085	an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy	1042:1140	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	9	44	theme	therapeutic	1348:1358	arg1	antibodies					1360:1369	edible therapeutic antibodies	1341:1369	edible therapeutic antibodies such as those for the treatment of mucosal infection	1341:1422	These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection.
28368034	9	44	theme	therapeutic	1348:1358	arg1	those					1379:1383	those	1379:1383	those	1379:1383	These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection.
28368034	5	45	theme	secretory	704:712	arg1	component					714:722	J chain and secretory component	692:722	component	714:722	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	5	45	theme	secretory	704:712	arg1	heavy					678:682	heavy	678:682	heavy	678:682	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	0	46	theme	Cells	26:30	arg1	Protection					0:9	Protection	0:9	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.	0:89	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	3	47	theme	mouse	533:537	arg1	IgA					539:541	mouse IgA	533:541	mouse IgA	533:541	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	2	48	theme	immunoglobulin	203:216	arg1	SIgA					226:229	SIgA	226:229	SIgA	226:229	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	2	48	theme	immunoglobulin	203:216	arg1	A					223:223	Secretory immunoglobulin (Ig) A	193:223	Secretory immunoglobulin (Ig) A (SIgA)	193:230	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	6	49	theme	antigen	904:910	arg1	binding					912:918	antigen binding	904:918	antigen binding	904:918	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	4	50	theme	secretory	563:571	arg1	form					573:576	a secretory form	561:576	a secretory form of the recombinant IgA (S-hyIgA)	561:609	Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant.
28368034	8	51	theme	colon	1262:1266	arg1	line					1283:1286	human colon carcinoma cell line	1256:1286	a human colon carcinoma cell line	1254:1286	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	8	51	theme	colon	1262:1266	arg1	cells					1247:1251	butyrate-treated Caco-2 cells	1223:1251	butyrate-treated Caco-2 cells	1223:1251	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	3	52	theme	IgA	539:541	arg1	antibody					388:395	a recombinant monoclonal antibody	363:395	a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	363:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	3	52	theme	IgA	539:541	arg1	region					523:528	the Fc region	516:528	the Fc region of mouse IgA	516:541	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	3	52	theme	IgA	539:541	arg1	mAb					398:400	mAb	398:400	mAb	398:400	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	2	53	theme	Secretory	193:201	arg1	SIgA					226:229	SIgA	226:229	SIgA	226:229	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	2	53	theme	Secretory	193:201	arg1	A					223:223	Secretory immunoglobulin (Ig) A	193:223	Secretory immunoglobulin (Ig) A (SIgA)	193:230	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	8	54	theme	human	1256:1260	arg1	line					1283:1286	human colon carcinoma cell line	1256:1286	a human colon carcinoma cell line	1254:1286	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	8	54	theme	human	1256:1260	arg1	cells					1247:1251	butyrate-treated Caco-2 cells	1223:1251	butyrate-treated Caco-2 cells	1223:1251	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	5	55	theme	bidirectional	763:775	arg1	promoter					777:784	a bidirectional promoter	761:784	a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana	761:836	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	0	56	theme	Shiga	37:41	arg1	Toxin					43:47	Shiga Toxin	37:47	Shiga Toxin	37:47	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	3	57	theme	variable	417:424	arg1	regions					426:432	variable regions	417:432	variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1)	417:510	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	6	58	link	N-linked	958:965	arg1	chains					973:978	plant-specific N-linked sugar chains	943:978	plant-specific N-linked sugar chains	943:978	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	2	59	theme	surface	280:286	arg1	infection					255:263	infection	255:263	infection of the mucosal surface	255:286	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	3	60	theme	Fc	520:521	arg1	region					523:528	the Fc region	516:528	the Fc region of mouse IgA	516:541	We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA.
28368034	8	61	theme	transgenic	1161:1170	arg1	extract					1146:1152	An extract	1143:1152	An extract of the transgenic leaves	1143:1177	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	5	62	theme	promoter	777:784	arg1	control					750:756	the control	746:756	the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana	746:836	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	7	63	theme	secretory	1004:1012	arg1	components					1014:1023	secretory components	1004:1023	secretory components	1004:1023	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
28368034	9	64	theme	infection	1414:1422	arg1	treatment					1393:1401	the treatment	1389:1401	the treatment of mucosal infection	1389:1422	These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection.
28368034	1	65	theme	major	108:112	arg1	factor					124:129	a major virulence factor	106:129	a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7	106:190	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	1	65	theme	major	108:112	arg1	toxin					97:101	Shiga toxin	91:101	Shiga toxin	91:101	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	5	66	theme	protein	815:821	arg1	promoter					777:784	a bidirectional promoter	761:784	a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana	761:836	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	5	67	theme	J	692:692	arg1	chain					694:698	J chain and secretory component	692:722	chain	694:698	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	5	67	theme	J	692:692	arg1	heavy					678:682	heavy	678:682	heavy	678:682	All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter.
28368034	8	68	dep	transgenic	1161:1170	arg1	leaves					1172:1177	leaves	1172:1177	leaves	1172:1177	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	1	69	theme	virulence	114:122	arg1	factor					124:129	a major virulence factor	106:129	a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7	106:190	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	1	69	theme	virulence	114:122	arg1	toxin					97:101	Shiga toxin	91:101	Shiga toxin	91:101	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	8	70	theme	Caco-2	1240:1245	arg1	line					1283:1286	human colon carcinoma cell line	1256:1286	a human colon carcinoma cell line	1254:1286	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	8	70	theme	Caco-2	1240:1245	arg1	cells					1247:1251	butyrate-treated Caco-2 cells	1223:1251	butyrate-treated Caco-2 cells	1223:1251	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	2	71	theme	mucosal	272:278	arg1	surface					280:286	the mucosal surface	268:286	the mucosal surface	268:286	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	0	72	theme	Plant-based	52:62	arg1	IgA					86:88	Plant-based Recombinant Secretory IgA	52:88	Plant-based Recombinant Secretory IgA	52:88	Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA.
28368034	8	73	theme	cell	1278:1281	arg1	line					1283:1286	human colon carcinoma cell line	1256:1286	a human colon carcinoma cell line	1254:1286	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	8	73	theme	cell	1278:1281	arg1	cells					1247:1251	butyrate-treated Caco-2 cells	1223:1251	butyrate-treated Caco-2 cells	1223:1251	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	8	74	theme	Stx1	1211:1214	arg1	cytotoxicity					1195:1206	the cytotoxicity	1191:1206	the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line	1191:1286	An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line.
28368034	6	75	mod	modified	929:936	arg3	chains					973:978	plant-specific N-linked sugar chains	943:978	plant-specific N-linked sugar chains	943:978	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	6	75	mod	modified	929:936	arg1	S-hyIgA					886:892	The plant-based S-hyIgA	870:892	The plant-based S-hyIgA	870:892	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	6	76	theme	plant-based	874:884	arg1	S-hyIgA					886:892	The plant-based S-hyIgA	870:892	The plant-based S-hyIgA	870:892	The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains.
28368034	9	77	theme	edible	1341:1346	arg1	antibodies					1360:1369	edible therapeutic antibodies	1341:1369	edible therapeutic antibodies such as those for the treatment of mucosal infection	1341:1422	These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection.
28368034	9	77	theme	edible	1341:1346	arg1	those					1379:1383	those	1379:1383	those	1379:1383	These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection.
28368034	1	78	dep	O157	184:187	arg1	H7					189:190	H7	189:190	O157:H7	184:190	Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7.
28368034	2	79	theme	candidate	297:305	arg1	agent					307:311	a candidate agent	295:311	a candidate agent for oral immunotherapy	295:334	Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy.
28368034	7	80	theme	immuno-electron	1115:1129	arg1	microscopy					1131:1140	immuno-electron microscopy	1115:1140	immuno-electron microscopy	1115:1140	The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy.
31010828	3	0	from	cells	811:815	arg1	present					787:793	present	787:793	present	787:793	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	1	theme	master	969:974	arg1	factor					990:995	the Th17 master transcription factor	960:995	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	2	theme	intracellular	1128:1140	arg1	microenvironment					1148:1163	the intracellular lipid microenvironment	1124:1163	the intracellular lipid microenvironment	1124:1163	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	3	theme	elevated	867:874	arg1	levels					885:890	elevated O-GlcNAc levels	867:890	elevated O-GlcNAc levels	867:890	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	0	4	theme	lipid	95:99	arg1	microenvironment					101:116	the intracellular lipid microenvironment	77:116	the intracellular lipid microenvironment	77:116	Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment.
31010828	3	5	attach	present	787:793	arg2	levels					697:702	increased levels	687:702	increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc,	687:781	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	5	attach	present	787:793	arg1	cells					811:815	naive CD4+ T cells	798:815	naive CD4+ T cells from a diet-induced obesity murine model	798:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	5	6	theme	ligands	1427:1433	arg1	production					1390:1399	production	1390:1399	production of these RORγt-activating ligands	1390:1433	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	4	7	theme	IL-17	1052:1056	arg1	promoter					1063:1070	the IL-17 gene promoter	1048:1070	the IL-17 gene promoter	1048:1070	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	8	theme	ChIP	614:617	arg1	assays					619:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	9	dep	factor	990:995	arg1	RORγt					1038:1042	RORγt	1038:1042	RORγt	1038:1042	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	9	dep	factor	990:995	arg1	variant					1029:1035	RAR-related orphan receptor γ t variant	997:1035	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	10	from	model	852:856	arg1	cells					811:815	naive CD4+ T cells	798:815	naive CD4+ T cells from a diet-induced obesity murine model	798:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	2	11	theme	cells	292:296	arg1	Levels					258:263	Levels	258:263	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A),	258:337	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	3	12	theme	CD4+	804:807	arg1	cells					811:815	naive CD4+ T cells	798:815	naive CD4+ T cells from a diet-induced obesity murine model	798:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	2	13	theme	IL-17A-mediated	498:512	arg1	inflammation					514:525	IL-17A-mediated inflammation	498:525	IL-17A-mediated inflammation	498:525	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	6	14	theme	excess	1540:1545	arg1	levels					1556:1561	excess nutrient levels	1540:1561	excess nutrient levels	1540:1561	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	4	15	theme	transcriptional	1229:1243	arg1	activity					1245:1252	RORγt transcriptional activity	1223:1252	RORγt transcriptional activity	1223:1252	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	2	16	theme	Th17	286:289	arg1	cells					292:296	CD4+ T helper 17 (Th17) cells	268:296	CD4+ T helper 17 (Th17) cells	268:296	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	4	17	theme	transcription	976:988	arg1	factor					990:995	the Th17 master transcription factor	960:995	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	18	theme	T	809:809	arg1	cells					811:815	naive CD4+ T cells	798:815	naive CD4+ T cells from a diet-induced obesity murine model	798:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	5	19	theme	acetyl-CoA	1321:1330	arg1	carboxylase					1332:1342	acetyl-CoA carboxylase 1	1321:1344	acetyl-CoA carboxylase 1 (ACC1)	1321:1351	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	5	19	theme	acetyl-CoA	1321:1330	arg1	ACC1					1347:1350	ACC1	1347:1350	ACC1	1347:1350	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	5	19	theme	acetyl-CoA	1321:1330	arg1	enzyme					1286:1291	the rate-limiting enzyme	1268:1291	the rate-limiting enzyme of fatty acid biosynthesis	1268:1318	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	4	20	theme	RORγt	1223:1227	arg1	activity					1245:1252	RORγt transcriptional activity	1223:1252	RORγt transcriptional activity	1223:1252	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	21	theme	IL-17A	901:906	arg1	production					908:917	IL-17A production	901:917	IL-17A production	901:917	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	22	from	alterations	1109:1119	arg1	binding					949:955	increased binding	939:955	increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment,	939:1164	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	22	from	alterations	1109:1119	arg1	microenvironment					1148:1163	the intracellular lipid microenvironment	1124:1163	the intracellular lipid microenvironment	1124:1163	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	23	theme	increased	939:947	arg1	binding					949:955	increased binding	939:955	increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment,	939:1164	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	24	theme	increased	687:695	arg1	levels					697:702	increased levels	687:702	increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc,	687:781	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	25	theme	receptor	1016:1023	arg1	RORγt					1038:1042	RORγt	1038:1042	RORγt	1038:1042	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	25	theme	receptor	1016:1023	arg1	variant					1029:1035	RAR-related orphan receptor γ t variant	997:1035	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	26	theme	O-GlcNAc	876:883	arg1	levels					885:890	elevated O-GlcNAc levels	867:890	elevated O-GlcNAc levels	867:890	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	27	theme	γ	1025:1025	arg1	RORγt					1038:1042	RORγt	1038:1042	RORγt	1038:1042	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	27	theme	γ	1025:1025	arg1	variant					1029:1035	RAR-related orphan receptor γ t variant	997:1035	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	28	theme	Th17	964:967	arg1	factor					990:995	the Th17 master transcription factor	960:995	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	29	located	present	787:793	arg2	levels					697:702	increased levels	687:702	increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc,	687:781	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	29	located	present	787:793	arg1	cells					811:815	naive CD4+ T cells	798:815	naive CD4+ T cells from a diet-induced obesity murine model	798:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	1	30	from	risk	165:168	arg1	diabetes					248:255	diabetes	248:255	diabetes	248:255	Chronic, low-grade inflammation increases the risk for atherosclerosis, cancer, and autoimmunity in diseases such as obesity and diabetes.
31010828	1	30	from	risk	165:168	arg1	diseases					219:226	diseases	219:226	diseases such as obesity and diabetes	219:255	Chronic, low-grade inflammation increases the risk for atherosclerosis, cancer, and autoimmunity in diseases such as obesity and diabetes.
31010828	1	30	from	risk	165:168	arg1	obesity					236:242	obesity	236:242	obesity	236:242	Chronic, low-grade inflammation increases the risk for atherosclerosis, cancer, and autoimmunity in diseases such as obesity and diabetes.
31010828	3	31	theme	cytokine	551:558	arg1	assays					619:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	32	theme	significant	1097:1107	arg1	alterations					1109:1119	significant alterations	1097:1119	significant alterations in the intracellular lipid microenvironment	1097:1163	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	0	33	theme	Elevated	0:7	arg1	O-GlcNAcylation					9:23	Elevated O-GlcNAcylation	0:23	Elevated O-GlcNAcylation	0:23	Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment.
31010828	3	34	theme	post-translational	732:749	arg1	O-GlcNAc					773:780	O-GlcNAc	773:780	O-GlcNAc	773:780	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	34	theme	post-translational	732:749	arg1	modification					759:770	the nutrient-responsive, post-translational protein modification	707:770	modification	759:770	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	6	35	theme	proteins	1499:1506	arg1	link					1527:1530	a potential link	1515:1530	a potential link between excess nutrient levels and pathological inflammation	1515:1591	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	6	35	theme	proteins	1499:1506	arg1	O-GlcNAcylation					1471:1485	increased O-GlcNAcylation	1461:1485	increased O-GlcNAcylation of cellular proteins	1461:1506	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	4	36	theme	capable	1201:1207	arg1	ligands					1193:1199	ligands	1193:1199	ligands capable of increasing RORγt transcriptional activity	1193:1252	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	1	37	theme	Chronic	119:125	arg1	inflammation					138:149	Chronic, low-grade inflammation	119:149	inflammation	138:149	Chronic, low-grade inflammation increases the risk for atherosclerosis, cancer, and autoimmunity in diseases such as obesity and diabetes.
31010828	5	38	theme	fatty	1296:1300	arg1	biosynthesis					1307:1318	fatty acid biosynthesis	1296:1318	fatty acid biosynthesis	1296:1318	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	0	39	theme	pro-inflammatory	34:49	arg1	function					56:63	pro-inflammatory Th17 function	34:63	pro-inflammatory Th17 function	34:63	Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment.
31010828	3	40	theme	protein	751:757	arg1	O-GlcNAc					773:780	O-GlcNAc	773:780	O-GlcNAc	773:780	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	40	theme	protein	751:757	arg1	modification					759:770	the nutrient-responsive, post-translational protein modification	707:770	modification	759:770	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	41	theme	ligands	1193:1199	arg1	production					1179:1188	the production	1175:1188	the production of ligands capable of increasing RORγt transcriptional activity	1175:1252	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	5	42	theme	acid	1302:1305	arg1	biosynthesis					1307:1318	fatty acid biosynthesis	1296:1318	fatty acid biosynthesis	1296:1318	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	4	43	theme	t	1027:1027	arg1	RORγt					1038:1042	RORγt	1038:1042	RORγt	1038:1042	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	43	theme	t	1027:1027	arg1	variant					1029:1035	RAR-related orphan receptor γ t variant	997:1035	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	44	theme	nutrient-responsive	711:729	arg1	O-GlcNAc					773:780	O-GlcNAc	773:780	O-GlcNAc	773:780	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	44	theme	nutrient-responsive	711:729	arg1	modification					759:770	the nutrient-responsive, post-translational protein modification	707:770	modification	759:770	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	1	45	theme	low-grade	128:136	arg1	inflammation					138:149	Chronic, low-grade inflammation	119:149	inflammation	138:149	Chronic, low-grade inflammation increases the risk for atherosclerosis, cancer, and autoimmunity in diseases such as obesity and diabetes.
31010828	5	46	theme	biosynthesis	1307:1318	arg1	carboxylase					1332:1342	acetyl-CoA carboxylase 1	1321:1344	acetyl-CoA carboxylase 1 (ACC1)	1321:1351	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	5	46	theme	biosynthesis	1307:1318	arg1	enzyme					1286:1291	the rate-limiting enzyme	1268:1291	the rate-limiting enzyme of fatty acid biosynthesis	1268:1318	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	5	46	theme	biosynthesis	1307:1318	arg1	O-GlcNAcylated					1357:1370	O-GlcNAcylated	1357:1370	O-GlcNAcylated	1357:1370	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	2	47	theme	inflammatory	386:397	arg1	milieu					399:404	the inflammatory milieu	382:404	the inflammatory milieu	382:404	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	4	48	theme	factor	990:995	arg1	binding					949:955	increased binding	939:955	increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment,	939:1164	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	6	49	theme	nutrient	1547:1554	arg1	levels					1556:1561	excess nutrient levels	1540:1561	excess nutrient levels	1540:1561	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	0	50	theme	intracellular	81:93	arg1	microenvironment					101:116	the intracellular lipid microenvironment	77:116	the intracellular lipid microenvironment	77:116	Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment.
31010828	3	51	theme	PCR	584:586	arg1	assays					619:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	52	theme	gene	1058:1061	arg1	promoter					1063:1070	the IL-17 gene promoter	1048:1070	the IL-17 gene promoter	1048:1070	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	53	from	enhancer	1076:1083	arg1	binding					949:955	increased binding	939:955	increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment,	939:1164	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	53	from	enhancer	1076:1083	arg1	microenvironment					1148:1163	the intracellular lipid microenvironment	1124:1163	the intracellular lipid microenvironment	1124:1163	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	2	54	theme	signaling	441:449	arg1	events					451:456	signaling events	441:456	signaling events triggered by excess nutrient levels	441:492	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	0	55	theme	Th17	51:54	arg1	function					56:63	pro-inflammatory Th17 function	34:63	pro-inflammatory Th17 function	34:63	Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment.
31010828	6	56	theme	pathological	1567:1578	arg1	inflammation					1580:1591	pathological inflammation	1567:1591	pathological inflammation	1567:1591	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	4	57	theme	orphan	1009:1014	arg1	RORγt					1038:1042	RORγt	1038:1042	RORγt	1038:1042	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	57	theme	orphan	1009:1014	arg1	variant					1029:1035	RAR-related orphan receptor γ t variant	997:1035	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	58	theme	quantitative	561:572	arg1	PCR					584:586	quantitative real-time PCR	561:586	quantitative real-time PCR	561:586	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	4	59	from	promoter	1063:1070	arg1	binding					949:955	increased binding	939:955	increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment,	939:1164	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	59	from	promoter	1063:1070	arg1	microenvironment					1148:1163	the intracellular lipid microenvironment	1124:1163	the intracellular lipid microenvironment	1124:1163	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	60	theme	RAR-related	997:1007	arg1	RORγt					1038:1042	RORγt	1038:1042	RORγt	1038:1042	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	4	60	theme	RAR-related	997:1007	arg1	variant					1029:1035	RAR-related orphan receptor γ t variant	997:1035	the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt)	960:1043	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
31010828	3	61	theme	modification	759:770	arg1	levels					697:702	increased levels	687:702	increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc,	687:781	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	62	from	present	787:793	arg1	cells					811:815	naive CD4+ T cells	798:815	naive CD4+ T cells from a diet-induced obesity murine model	798:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	63	theme	MS-based	653:660	arg1	approaches					662:671	MS-based approaches	653:671	MS-based approaches	653:671	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	64	theme	real-time	574:582	arg1	PCR					584:586	quantitative real-time PCR	561:586	quantitative real-time PCR	561:586	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	6	65	theme	increased	1461:1469	arg1	link					1527:1530	a potential link	1515:1530	a potential link between excess nutrient levels and pathological inflammation	1515:1591	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	6	65	theme	increased	1461:1469	arg1	O-GlcNAcylation					1471:1485	increased O-GlcNAcylation	1461:1485	increased O-GlcNAcylation of cellular proteins	1461:1506	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	3	66	theme	obesity	837:843	arg1	model					852:856	a diet-induced obesity murine model	822:856	a diet-induced obesity murine model	822:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	5	67	theme	RORγt-activating	1410:1425	arg1	ligands					1427:1433	these RORγt-activating ligands	1404:1433	these RORγt-activating ligands	1404:1433	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	6	68	theme	potential	1517:1525	arg1	O-GlcNAcylation					1471:1485	increased O-GlcNAcylation	1461:1485	increased O-GlcNAcylation of cellular proteins	1461:1506	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	6	68	theme	potential	1517:1525	arg1	link					1527:1530	a potential link	1515:1530	a potential link between excess nutrient levels and pathological inflammation	1515:1591	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	2	69	theme	helper	275:280	arg1	cells					292:296	CD4+ T helper 17 (Th17) cells	268:296	CD4+ T helper 17 (Th17) cells	268:296	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	3	70	theme	immunoprecipitation	589:607	arg1	assays					619:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays	551:624	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	71	theme	murine	845:850	arg1	model					852:856	a diet-induced obesity murine model	822:856	a diet-induced obesity murine model	822:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	2	72	theme	T	273:273	arg1	cells					292:296	CD4+ T helper 17 (Th17) cells	268:296	CD4+ T helper 17 (Th17) cells	268:296	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	5	73	theme	rate-limiting	1272:1284	arg1	carboxylase					1332:1342	acetyl-CoA carboxylase 1	1321:1344	acetyl-CoA carboxylase 1 (ACC1)	1321:1351	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	5	73	theme	rate-limiting	1272:1284	arg1	enzyme					1286:1291	the rate-limiting enzyme	1268:1291	the rate-limiting enzyme of fatty acid biosynthesis	1268:1318	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	5	73	theme	rate-limiting	1272:1284	arg1	O-GlcNAcylated					1357:1370	O-GlcNAcylated	1357:1370	O-GlcNAcylated	1357:1370	Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands.
31010828	2	74	theme	interleukin	313:323	arg1	IL-17A					330:335	IL-17A	330:335	IL-17A	330:335	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	2	74	theme	interleukin	313:323	arg1	17A					325:327	interleukin 17A	313:327	interleukin 17A (IL-17A)	313:336	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	6	75	theme	cellular	1490:1497	arg1	proteins					1499:1506	cellular proteins	1490:1506	cellular proteins	1490:1506	Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.
31010828	3	76	theme	naive	798:802	arg1	cells					811:815	naive CD4+ T cells	798:815	naive CD4+ T cells from a diet-induced obesity murine model	798:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	2	77	theme	nutrient	478:485	arg1	levels					487:492	excess nutrient levels	471:492	excess nutrient levels	471:492	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	2	78	theme	CD4+	268:271	arg1	cells					292:296	CD4+ T helper 17 (Th17) cells	268:296	CD4+ T helper 17 (Th17) cells	268:296	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	3	79	theme	diet-induced	824:835	arg1	model					852:856	a diet-induced obesity murine model	822:856	a diet-induced obesity murine model	822:856	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	3	80	dep	along	627:631	arg1	with					633:636	with	633:636	with	633:636	Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production.
31010828	2	81	theme	excess	471:476	arg1	levels					487:492	excess nutrient levels	471:492	excess nutrient levels	471:492	Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear.
31010828	4	82	theme	lipid	1142:1146	arg1	microenvironment					1148:1163	the intracellular lipid microenvironment	1124:1163	the intracellular lipid microenvironment	1124:1163	We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity.
27927990	2	0	theme	subsequent	365:374	arg1	studies					376:382	subsequent studies	365:382	subsequent studies	365:382	RFT1 was originally proposed to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) across the endoplasmic reticulum membrane, but subsequent studies showed that it does not play a direct role in transport.
27927990	1	1	theme	protein	91:97	arg1	RFT1					99:102	The membrane protein RFT1	78:102	The membrane protein RFT1	78:102	The membrane protein RFT1 is essential for normal protein N-glycosylation, but its precise function is not known.
27927990	1	1	theme	protein	91:97	arg1	essential					107:115	essential	107:115	essential	107:115	The membrane protein RFT1 is essential for normal protein N-glycosylation, but its precise function is not known.
27927990	2	2	theme	N-glycan	297:304	arg1	precursors					306:315	N-glycan precursors	297:315	N-glycan precursors	297:315	RFT1 was originally proposed to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) across the endoplasmic reticulum membrane, but subsequent studies showed that it does not play a direct role in transport.
27927990	7	3	gly	glycosylation	1662:1674	arg1	apparatus					1689:1697	the Golgi apparatus	1679:1697	the Golgi apparatus	1679:1697	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	5	4	theme	mass	837:840	arg1	spectrometry					842:853	mass spectrometry	837:853	mass spectrometry	837:853	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	6	5	theme	In	1122:1123	arg1	experiments					1152:1162	In vivo and in vitro labeling experiments	1122:1162	In vivo and in vitro labeling experiments using radiolabeled GPI precursors	1122:1196	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	6	dep	In	1122:1123	arg1	vivo					1125:1128	vivo	1125:1128	vivo	1125:1128	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	7	theme	GPI	1210:1212	arg1	result					1245:1250	the result	1241:1250	the result of decreased formation of the GPI precursor lipid	1241:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	7	theme	GPI	1210:1212	arg1	underglycosylation					1214:1231	GPI underglycosylation	1210:1231	GPI underglycosylation	1210:1231	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	7	8	theme	direct	1624:1629	arg1	role					1643:1646	a direct or indirect role	1622:1646	a direct or indirect role	1622:1646	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	5	9	contain	have	934:937	arg2	chains					965:970	truncated GPI anchor side chains	939:970	truncated GPI anchor side chains in TbRFT1 null parasites	939:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	5	9	contain	have	934:937	arg1	proteins					896:903	the major GPI-anchored proteins	873:903	the major GPI-anchored proteins of T. brucei procyclic forms	873:932	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	3	10	theme	brucei	552:557	arg1	growth					506:511	growth	506:511	growth of the parasitic protozoan Trypanosoma brucei	506:557	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	5	11	theme	metabolic	813:821	arg1	labeling					823:830	metabolic labeling	813:830	metabolic labeling	813:830	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	1	12	theme	normal	121:126	arg1	N-glycosylation					136:150	normal protein N-glycosylation	121:150	normal protein N-glycosylation	121:150	The membrane protein RFT1 is essential for normal protein N-glycosylation, but its precise function is not known.
27927990	6	13	theme	precursor	1286:1294	arg1	lipid					1296:1300	the GPI precursor lipid	1278:1300	the GPI precursor lipid	1278:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	4	14	dep	N-glycosylation	693:707	arg1	modification					771:782	side-chain modification	760:782	protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification	685:782	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	6	15	theme	radiolabeled	1170:1181	arg1	precursors					1187:1196	radiolabeled GPI precursors	1170:1196	radiolabeled GPI precursors	1170:1196	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	16	theme	formation	1265:1273	arg1	result					1245:1250	the result	1241:1250	the result of decreased formation of the GPI precursor lipid	1241:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	16	theme	formation	1265:1273	arg1	galactosylation					1315:1329	defective galactosylation	1305:1329	defective galactosylation of GPI intermediates in the endoplasmic reticulum	1305:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	16	theme	formation	1265:1273	arg1	underglycosylation					1214:1231	GPI underglycosylation	1210:1231	GPI underglycosylation	1210:1231	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	3	17	theme	null	600:603	arg1	background					605:614	a null background	598:614	a null background	598:614	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	8	18	theme	glycosylation	1747:1759	arg1	processes					1761:1769	glycosylation processes	1747:1769	glycosylation processes	1747:1769	Our results implicate RFT1 in a wider range of glycosylation processes than previously appreciated.
27927990	5	19	theme	T.	908:909	arg1	forms					928:932	T. brucei procyclic forms	908:932	T. brucei procyclic forms	908:932	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	7	20	from	glycosylation	1662:1674	arg1	apparatus					1689:1697	the Golgi apparatus	1679:1697	the Golgi apparatus	1679:1697	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	6	21	theme	endoplasmic	1359:1369	arg1	reticulum					1371:1379	the endoplasmic reticulum	1355:1379	the endoplasmic reticulum	1355:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	2	22	theme	glycolipid	240:249	arg1	Man5GlcNAc2-PP-dolichol					251:273	the glycolipid Man5GlcNAc2-PP-dolichol	236:273	the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors)	236:316	RFT1 was originally proposed to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) across the endoplasmic reticulum membrane, but subsequent studies showed that it does not play a direct role in transport.
27927990	6	23	from	reticulum	1371:1379	arg1	result					1245:1250	the result	1241:1250	the result of decreased formation of the GPI precursor lipid	1241:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	23	from	reticulum	1371:1379	arg1	galactosylation					1315:1329	defective galactosylation	1305:1329	defective galactosylation of GPI intermediates in the endoplasmic reticulum	1305:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	23	from	reticulum	1371:1379	arg1	underglycosylation					1214:1231	GPI underglycosylation	1210:1231	GPI underglycosylation	1210:1231	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	5	24	theme	GPI-anchored	883:894	arg1	proteins					896:903	the major GPI-anchored proteins	873:903	the major GPI-anchored proteins of T. brucei procyclic forms	873:932	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	4	25	theme	glycosylphosphatidylinositol	718:745	arg1	anchor					753:758	glycosylphosphatidylinositol (GPI) anchor	718:758	protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification	685:782	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	6	26	theme	GPI	1334:1336	arg1	intermediates					1338:1350	GPI intermediates	1334:1350	GPI intermediates in the endoplasmic reticulum	1334:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	3	27	theme	protozoan	530:538	arg1	brucei					552:557	the parasitic protozoan Trypanosoma brucei	516:557	the parasitic protozoan Trypanosoma brucei	516:557	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	5	28	theme	anchor	953:958	arg1	chains					965:970	truncated GPI anchor side chains	939:970	truncated GPI anchor side chains in TbRFT1 null parasites	939:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	7	29	theme	endoplasmic	1538:1548	arg1	reticulum					1550:1558	the endoplasmic reticulum	1534:1558	the endoplasmic reticulum	1534:1558	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	6	30	from	intermediates	1338:1350	arg1	reticulum					1371:1379	the endoplasmic reticulum	1355:1379	the endoplasmic reticulum	1355:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	1	31	theme	membrane	82:89	arg1	RFT1					99:102	The membrane protein RFT1	78:102	The membrane protein RFT1	78:102	The membrane protein RFT1 is essential for normal protein N-glycosylation, but its precise function is not known.
27927990	1	31	theme	membrane	82:89	arg1	essential					107:115	essential	107:115	essential	107:115	The membrane protein RFT1 is essential for normal protein N-glycosylation, but its precise function is not known.
27927990	7	32	theme	GPI	1651:1653	arg1	glycosylation					1662:1674	GPI anchor glycosylation	1651:1674	GPI anchor glycosylation in the Golgi apparatus	1651:1697	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	4	33	theme	protein	685:691	arg1	N-glycosylation					693:707	protein N-glycosylation	685:707	protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification	685:782	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	0	34	theme	RFT1	0:3	arg1	Protein					5:11	RFT1 Protein	0:11	RFT1 Protein	0:11	RFT1 Protein Affects Glycosylphosphatidylinositol (GPI) Anchor Glycosylation.
27927990	5	35	theme	forms	928:932	arg1	proteins					896:903	the major GPI-anchored proteins	873:903	the major GPI-anchored proteins of T. brucei procyclic forms	873:932	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	3	36	from	study	573:577	arg1	background					605:614	a null background	598:614	a null background	598:614	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	5	37	theme	truncated	939:947	arg1	anchor					953:958	truncated GPI anchor	939:958	truncated GPI anchor side chains in TbRFT1 null parasites	939:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	2	38	theme	direct	415:420	arg1	role					422:425	a direct role	413:425	a direct role	413:425	RFT1 was originally proposed to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) across the endoplasmic reticulum membrane, but subsequent studies showed that it does not play a direct role in transport.
27927990	5	39	theme	null	1105:1108	arg1	background					1110:1119	the null background	1101:1119	the null background	1101:1119	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	7	40	theme	immunofluorescence	1479:1496	arg1	microscopy					1498:1507	immunofluorescence microscopy	1479:1507	immunofluorescence microscopy	1479:1507	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	5	41	theme	wild-type	1016:1024	arg1	cells					1026:1030	wild-type cells	1016:1030	wild-type cells	1016:1030	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	5	41	theme	wild-type	1016:1024	arg1	defect					1035:1040	a defect	1033:1040	a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background	1033:1119	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	6	42	from	result	1245:1250	arg1	reticulum					1371:1379	the endoplasmic reticulum	1355:1379	the endoplasmic reticulum	1355:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	4	43	dep	lack	636:639	arg1	only					672:675	only	672:675	only	672:675	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	8	44	dep	range	1738:1742	arg1	appreciated					1787:1797	appreciated	1787:1797	appreciated	1787:1797	Our results implicate RFT1 in a wider range of glycosylation processes than previously appreciated.
27927990	6	45	theme	decreased	1255:1263	arg1	formation					1265:1273	decreased formation	1255:1273	decreased formation of the GPI precursor lipid	1255:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	5	46	from	chains	965:970	arg1	parasites					987:995	TbRFT1 null parasites	975:995	TbRFT1 null parasites	975:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	3	47	from	background	605:614	arg1	study					573:577	the study	569:577	the study of its function in a null background	569:614	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	3	48	theme	parasitic	520:528	arg1	brucei					552:557	the parasitic protozoan Trypanosoma brucei	516:557	the parasitic protozoan Trypanosoma brucei	516:557	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	8	49	theme	processes	1761:1769	arg1	range					1738:1742	a wider range	1730:1742	a wider range of glycosylation processes than previously appreciated	1730:1797	Our results implicate RFT1 in a wider range of glycosylation processes than previously appreciated.
27927990	6	50	theme	in	1134:1135	arg1	experiments					1152:1162	In vivo and in vitro labeling experiments	1122:1162	In vivo and in vitro labeling experiments using radiolabeled GPI precursors	1122:1196	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	2	51	theme	endoplasmic	329:339	arg1	reticulum					341:349	the endoplasmic reticulum	325:349	the endoplasmic reticulum membrane	325:358	RFT1 was originally proposed to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) across the endoplasmic reticulum membrane, but subsequent studies showed that it does not play a direct role in transport.
27927990	6	52	theme	defective	1305:1313	arg1	galactosylation					1315:1329	defective galactosylation	1305:1329	defective galactosylation of GPI intermediates in the endoplasmic reticulum	1305:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	3	53	theme	Trypanosoma	540:550	arg1	brucei					552:557	the parasitic protozoan Trypanosoma brucei	516:557	the parasitic protozoan Trypanosoma brucei	516:557	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	1	54	theme	precise	161:167	arg1	function					169:176	its precise function	157:176	its precise function	157:176	The membrane protein RFT1 is essential for normal protein N-glycosylation, but its precise function is not known.
27927990	6	55	theme	lipid	1296:1300	arg1	formation					1265:1273	decreased formation	1255:1273	decreased formation of the GPI precursor lipid	1255:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	56	dep	in	1134:1135	arg1	vitro					1137:1141	vitro	1137:1141	vitro	1137:1141	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	57	theme	GPI	1282:1284	arg1	lipid					1296:1300	the GPI precursor lipid	1278:1300	the GPI precursor lipid	1278:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	58	theme	GPI	1183:1185	arg1	precursors					1187:1196	radiolabeled GPI precursors	1170:1196	radiolabeled GPI precursors	1170:1196	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	8	59	theme	wider	1732:1736	arg1	range					1738:1742	a wider range	1730:1742	a wider range of glycosylation processes than previously appreciated	1730:1797	Our results implicate RFT1 in a wider range of glycosylation processes than previously appreciated.
27927990	1	60	theme	protein	128:134	arg1	N-glycosylation					136:150	normal protein N-glycosylation	121:150	normal protein N-glycosylation	121:150	The membrane protein RFT1 is essential for normal protein N-glycosylation, but its precise function is not known.
27927990	5	61	dep	T.	908:909	arg1	brucei					911:916	brucei	911:916	brucei	911:916	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	3	62	theme	function	586:593	arg1	study					573:577	the study	569:577	the study of its function in a null background	569:614	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	6	63	theme	labeling	1143:1150	arg1	experiments					1152:1162	In vivo and in vitro labeling experiments	1122:1162	In vivo and in vitro labeling experiments using radiolabeled GPI precursors	1122:1196	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	4	64	theme	T.	644:645	arg1	RFT1					654:657	T. brucei RFT1	644:657	T. brucei RFT1 (TbRFT1)	644:666	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	4	64	theme	T.	644:645	arg1	TbRFT1					660:665	TbRFT1	660:665	TbRFT1	660:665	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	5	65	theme	TbRFT1	1091:1096	arg1	copy					1083:1086	a tagged copy	1074:1086	a tagged copy of TbRFT1	1074:1096	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	7	66	with	consistent	1575:1584	arg1	proposal					1595:1602	the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus	1591:1697	the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus	1591:1697	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	5	67	theme	major	877:881	arg1	proteins					896:903	the major GPI-anchored proteins	873:903	the major GPI-anchored proteins of T. brucei procyclic forms	873:932	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	4	68	theme	RFT1	654:657	arg1	lack					636:639	lack	636:639	lack of T. brucei RFT1 (TbRFT1)	636:666	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	6	69	theme	intermediates	1338:1350	arg1	result					1245:1250	the result	1241:1250	the result of decreased formation of the GPI precursor lipid	1241:1300	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	69	theme	intermediates	1338:1350	arg1	galactosylation					1315:1329	defective galactosylation	1305:1329	defective galactosylation of GPI intermediates in the endoplasmic reticulum	1305:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	6	69	theme	intermediates	1338:1350	arg1	underglycosylation					1214:1231	GPI underglycosylation	1210:1231	GPI underglycosylation	1210:1231	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	5	70	theme	TbRFT1	975:980	arg1	parasites					987:995	TbRFT1 null parasites	975:995	TbRFT1 null parasites	975:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	5	71	theme	GPI	949:951	arg1	anchor					953:958	truncated GPI anchor	939:958	truncated GPI anchor side chains in TbRFT1 null parasites	939:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	7	72	theme	Golgi	1683:1687	arg1	apparatus					1689:1697	the Golgi apparatus	1679:1697	the Golgi apparatus	1679:1697	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	3	73	from	function	586:593	arg1	background					605:614	a null background	598:614	a null background	598:614	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	6	74	from	galactosylation	1315:1329	arg1	reticulum					1371:1379	the endoplasmic reticulum	1355:1379	the endoplasmic reticulum	1355:1379	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	5	75	theme	side	960:963	arg1	chains					965:970	truncated GPI anchor side chains	939:970	truncated GPI anchor side chains in TbRFT1 null parasites	939:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	5	76	theme	procyclic	918:926	arg1	forms					928:932	T. brucei procyclic forms	908:932	T. brucei procyclic forms	908:932	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	7	77	theme	anchor	1655:1660	arg1	glycosylation					1662:1674	GPI anchor glycosylation	1651:1674	GPI anchor glycosylation in the Golgi apparatus	1651:1697	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	0	78	theme	Glycosylphosphatidylinositol	21:48	arg1	Glycosylation					63:75	Glycosylphosphatidylinositol (GPI) Anchor Glycosylation	21:75	Glycosylphosphatidylinositol (GPI) Anchor Glycosylation	21:75	RFT1 Protein Affects Glycosylphosphatidylinositol (GPI) Anchor Glycosylation.
27927990	3	79	dep	situation	460:468	arg1	contrast					444:451	contrast	444:451	contrast	444:451	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	7	80	theme	indirect	1634:1641	arg1	role					1643:1646	a direct or indirect role	1622:1646	a direct or indirect role	1622:1646	Unexpectedly, immunofluorescence microscopy localized TbRFT1 to both the endoplasmic reticulum and the Golgi, consistent with the proposal that TbRFT1 plays a direct or indirect role in GPI anchor glycosylation in the Golgi apparatus.
27927990	0	81	theme	Anchor	56:61	arg1	Glycosylation					63:75	Glycosylphosphatidylinositol (GPI) Anchor Glycosylation	21:75	Glycosylphosphatidylinositol (GPI) Anchor Glycosylation	21:75	RFT1 Protein Affects Glycosylphosphatidylinositol (GPI) Anchor Glycosylation.
27927990	5	82	theme	tagged	1076:1081	arg1	copy					1083:1086	a tagged copy	1074:1086	a tagged copy of TbRFT1	1074:1096	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	3	83	from	situation	460:468	arg1	yeast					473:477	yeast	473:477	yeast	473:477	In contrast to the situation in yeast, RFT1 is not essential for growth of the parasitic protozoan Trypanosoma brucei, enabling the study of its function in a null background.
27927990	4	84	dep	T.	644:645	arg1	brucei					647:652	brucei	647:652	brucei	647:652	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
27927990	2	85	theme	reticulum	341:349	arg1	membrane					351:358	the endoplasmic reticulum membrane	325:358	the endoplasmic reticulum membrane	325:358	RFT1 was originally proposed to translocate the glycolipid Man5GlcNAc2-PP-dolichol (needed to synthesize N-glycan precursors) across the endoplasmic reticulum membrane, but subsequent studies showed that it does not play a direct role in transport.
27927990	6	86	theme	Golgi	1448:1452	arg1	apparatus					1454:1462	the Golgi apparatus	1444:1462	the Golgi apparatus	1444:1462	In vivo and in vitro labeling experiments using radiolabeled GPI precursors showed that GPI underglycosylation was not the result of decreased formation of the GPI precursor lipid or defective galactosylation of GPI intermediates in the endoplasmic reticulum, but rather due to modifications that are expected to occur in the Golgi apparatus.
27927990	5	87	theme	null	982:985	arg1	parasites					987:995	TbRFT1 null parasites	975:995	TbRFT1 null parasites	975:995	Analysis by immunoblotting, metabolic labeling, and mass spectrometry demonstrated that the major GPI-anchored proteins of T. brucei procyclic forms have truncated GPI anchor side chains in TbRFT1 null parasites when compared with wild-type cells, a defect that is corrected by expressing a tagged copy of TbRFT1 in the null background.
27927990	4	88	theme	side-chain	760:769	arg1	modification					771:782	side-chain modification	760:782	protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification	685:782	We now report that lack of T. brucei RFT1 (TbRFT1) not only affects protein N-glycosylation but also glycosylphosphatidylinositol (GPI) anchor side-chain modification.
30657688	0	0	theme	Copper-Free	73:83	arg1	Chemistry					91:99	Copper-Free Click Chemistry	73:99	Copper-Free Click Chemistry	73:99	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	1	1	theme	cellular	361:368	arg1	metabolism					370:379	cellular metabolism	361:379	cellular metabolism	361:379	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	2	link	O-linked	222:229	arg1	O-GlcNAc					256:263	O-GlcNAc	256:263	O-GlcNAc	256:263	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	2	link	O-linked	222:229	arg1	N-acetylglucosamine					234:252	O-linked β- N-acetylglucosamine	222:252	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins	222:313	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	3	dep	O-GlcNAcylation	286:300	arg1	i.e.					280:283	i.e.	280:283	i.e.	280:283	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	6	4	theme	synthetic	1100:1108	arg1	gCTD					1118:1121	standard synthetic peptide gCTD	1091:1121	standard synthetic peptide gCTD	1091:1121	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	3	5	theme	O-GlcNAc	569:576	arg1	enrichment					578:587	O-GlcNAc enrichment	569:587	O-GlcNAc enrichment	569:587	Herein we present a novel method for O-GlcNAc enrichment and site mapping.
30657688	0	6	theme	Click	85:89	arg1	Chemistry					91:99	Copper-Free Click Chemistry	73:99	Copper-Free Click Chemistry	73:99	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	5	7	theme	dissociation	1024:1035	arg1	analysis					1055:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	4	8	theme	disulfide	799:807	arg1	bridge					809:814	a disulfide bridge	797:814	a disulfide bridge	797:814	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	0	9	theme	Reductive	102:110	arg1	Cleavage					112:119	Reductive Cleavage	102:119	Reductive Cleavage	102:119	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	7	10	theme	site-specific	1375:1387	arg1	characterization					1389:1404	the site-specific characterization	1371:1404	the site-specific characterization of O-GlcNAcylation of important proteins	1371:1445	Our method provides a promising tool for the site-specific characterization of O-GlcNAcylation of important proteins.
30657688	5	11	theme	mass	1037:1040	arg1	analysis					1055:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	2	12	theme	site	414:417	arg1	mapping					419:425	O-GlcNAc site mapping	405:425	O-GlcNAc site mapping	405:425	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	2	12	theme	site	414:417	arg1	prerequisite					430:441	a prerequisite	428:441	a prerequisite for site-specific functional characterization	428:487	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	2	12	theme	site	414:417	arg1	challenge					501:509	a challenge	499:509	a challenge	499:509	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	7	13	theme	O-GlcNAcylation	1409:1423	arg1	characterization					1389:1404	the site-specific characterization	1371:1404	the site-specific characterization of O-GlcNAcylation of important proteins	1371:1445	Our method provides a promising tool for the site-specific characterization of O-GlcNAcylation of important proteins.
30657688	6	14	theme	peptide	1110:1116	arg1	gCTD					1118:1121	standard synthetic peptide gCTD	1091:1121	standard synthetic peptide gCTD	1091:1121	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	4	15	with	cycloaddition	720:732	arg1	reagent					757:763	a multifunctional reagent	739:763	a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle	739:835	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	5	16	theme	spectrometry	1042:1053	arg1	analysis					1055:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	0	17	theme	Site	9:12	arg1	Mapping					14:20	O-GlcNAc Site Mapping	0:20	O-GlcNAc Site Mapping	0:20	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	6	18	theme	kinase	1237:1242	arg1	protein					1261:1267	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2	1207:1269	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2)	1207:1276	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	6	18	theme	kinase	1237:1242	arg1	TAB2					1272:1275	TAB2	1272:1275	TAB2	1272:1275	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	1	19	theme	dynamic	181:187	arg1	modification					208:219	a dynamic post-translational modification	179:219	a dynamic post-translational modification	179:219	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	19	theme	dynamic	181:187	arg1	processes					341:349	many biological processes	325:349	many biological processes involving cellular metabolism and signaling	325:393	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	0	20	theme	O-GlcNAc	0:7	arg1	Mapping					14:20	O-GlcNAc Site Mapping	0:20	O-GlcNAc Site Mapping	0:20	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	4	21	theme	terminal	775:782	arg1	cyclooctyne					784:794	a terminal cyclooctyne	773:794	a terminal cyclooctyne	773:794	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	1	22	theme	post-translational	189:206	arg1	modification					208:219	a dynamic post-translational modification	179:219	a dynamic post-translational modification	179:219	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	22	theme	post-translational	189:206	arg1	processes					341:349	many biological processes	325:349	many biological processes involving cellular metabolism and signaling	325:393	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	5	23	theme	tagged	842:847	arg1	peptides					849:856	The tagged peptides	838:856	The tagged peptides	838:856	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	6	24	theme	overexpressed	1207:1219	arg1	protein					1261:1267	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2	1207:1269	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2)	1207:1276	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	6	24	theme	overexpressed	1207:1219	arg1	TAB2					1272:1275	TAB2	1272:1275	TAB2	1272:1275	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	2	25	theme	site-specific	447:459	arg1	characterization					472:487	site-specific functional characterization	447:487	site-specific functional characterization	447:487	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	2	26	theme	functional	461:470	arg1	characterization					472:487	site-specific functional characterization	447:487	site-specific functional characterization	447:487	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	4	27	theme	O-GlcNAc	627:634	arg1	moiety					636:641	the O-GlcNAc moiety	623:641	the O-GlcNAc moiety on peptides	623:653	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	3	28	theme	site	593:596	arg1	mapping					598:604	site mapping	593:604	site mapping	593:604	Herein we present a novel method for O-GlcNAc enrichment and site mapping.
30657688	6	29	theme	TGF-β-activated	1221:1235	arg1	protein					1261:1267	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2	1207:1269	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2)	1207:1276	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	6	29	theme	TGF-β-activated	1221:1235	arg1	TAB2					1272:1275	TAB2	1272:1275	TAB2	1272:1275	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	1	30	theme	proteins	306:313	arg1	O-GlcNAcylation					286:300	O-GlcNAcylation	286:300	O-GlcNAcylation	286:300	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	30	theme	proteins	306:313	arg1	modification					266:277	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification	222:277	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins	222:313	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	0	31	theme	Electron-Transfer	126:142	arg1	Spectrometry					162:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	2	32	theme	O-GlcNAc	405:412	arg1	mapping					419:425	O-GlcNAc site mapping	405:425	O-GlcNAc site mapping	405:425	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	2	32	theme	O-GlcNAc	405:412	arg1	prerequisite					430:441	a prerequisite	428:441	a prerequisite for site-specific functional characterization	428:487	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	2	32	theme	O-GlcNAc	405:412	arg1	challenge					501:509	a challenge	499:509	a challenge	499:509	However, O-GlcNAc site mapping, a prerequisite for site-specific functional characterization, has been a challenge since its discovery.
30657688	1	33	theme	O-linked	222:229	arg1	O-GlcNAc					256:263	O-GlcNAc	256:263	O-GlcNAc	256:263	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	33	theme	O-linked	222:229	arg1	N-acetylglucosamine					234:252	O-linked β- N-acetylglucosamine	222:252	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins	222:313	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	4	34	theme	copper-free	695:705	arg1	cycloaddition					720:732	copper-free azide-alkyne cycloaddition	695:732	copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle	695:835	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	5	35	theme	reductant	905:913	arg1	treatment					915:923	reductant treatment	905:923	reductant treatment	905:923	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	6	36	theme	O-GlcNAc	1289:1296	arg1	sites					1298:1302	four O-GlcNAc sites	1284:1302	four O-GlcNAc sites unambiguously identified	1284:1327	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	1	37	theme	β-	231:232	arg1	O-GlcNAc					256:263	O-GlcNAc	256:263	O-GlcNAc	256:263	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	37	theme	β-	231:232	arg1	N-acetylglucosamine					234:252	O-linked β- N-acetylglucosamine	222:252	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins	222:313	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	38	theme	many	325:328	arg1	modification					208:219	a dynamic post-translational modification	179:219	a dynamic post-translational modification	179:219	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	38	theme	many	325:328	arg1	processes					341:349	many biological processes	325:349	many biological processes involving cellular metabolism and signaling	325:393	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	0	39	theme	Mass	157:160	arg1	Spectrometry					162:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	4	40	from	moiety	636:641	arg1	peptides					646:653	peptides	646:653	peptides	646:653	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	5	41	theme	3-acrylamidopropyl	942:959	arg1	chloride					979:986	(3-acrylamidopropyl)trimethylammonium chloride	941:986	(3-acrylamidopropyl)trimethylammonium chloride	941:986	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	6	42	theme	protein	1133:1139	arg1	α-crystallin					1141:1152	model protein α-crystallin	1127:1152	model protein α-crystallin	1127:1152	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	1	43	theme	biological	330:339	arg1	modification					208:219	a dynamic post-translational modification	179:219	a dynamic post-translational modification	179:219	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	43	theme	biological	330:339	arg1	processes					341:349	many biological processes	325:349	many biological processes involving cellular metabolism and signaling	325:393	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	0	44	theme	Dissociation	144:155	arg1	Spectrometry					162:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	5	45	attach	released	868:875	arg2	peptides					849:856	The tagged peptides	838:856	The tagged peptides	838:856	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	5	45	attach	released	868:875	arg1	beads					894:898	NeutrAvidin beads	882:898	NeutrAvidin beads	882:898	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	4	46	theme	multifunctional	741:755	arg1	reagent					757:763	a multifunctional reagent	739:763	a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle	739:835	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	1	47	mod	modification	266:277	arg3	N-acetylglucosamine					234:252	O-linked β- N-acetylglucosamine	222:252	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins	222:313	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	47	mod	modification	266:277	arg3	O-GlcNAc					256:263	O-GlcNAc	256:263	O-GlcNAc	256:263	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	47	mod	modification	266:277	arg1	proteins					306:313	proteins	306:313	proteins	306:313	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	4	48	theme	biotin	823:828	arg1	handle					830:835	a biotin handle	821:835	a biotin handle	821:835	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	5	49	theme	trimethylammonium	961:977	arg1	chloride					979:986	(3-acrylamidopropyl)trimethylammonium chloride	941:986	(3-acrylamidopropyl)trimethylammonium chloride	941:986	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	1	50	theme	N-acetylglucosamine	234:252	arg1	O-GlcNAcylation					286:300	O-GlcNAcylation	286:300	O-GlcNAcylation	286:300	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	1	50	theme	N-acetylglucosamine	234:252	arg1	modification					266:277	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification	222:277	O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins	222:313	As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling.
30657688	6	51	theme	1/MAP3K7	1244:1251	arg1	protein					1261:1267	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2	1207:1269	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2)	1207:1276	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	6	51	theme	1/MAP3K7	1244:1251	arg1	TAB2					1272:1275	TAB2	1272:1275	TAB2	1272:1275	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	7	52	theme	promising	1352:1360	arg1	tool					1362:1365	a promising tool	1350:1365	a promising tool for the site-specific characterization of O-GlcNAcylation of important proteins	1350:1445	Our method provides a promising tool for the site-specific characterization of O-GlcNAcylation of important proteins.
30657688	5	53	theme	electron-transfer	1006:1022	arg1	analysis					1055:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	electron-transfer dissociation mass spectrometry analysis	1006:1062	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	4	54	theme	azide-alkyne	707:718	arg1	cycloaddition					720:732	copper-free azide-alkyne cycloaddition	695:732	copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle	695:835	In this method, the O-GlcNAc moiety on peptides was labeled with UDP-GalNAz followed by copper-free azide-alkyne cycloaddition with a multifunctional reagent bearing a terminal cyclooctyne, a disulfide bridge, and a biotin handle.
30657688	6	55	theme	standard	1091:1098	arg1	gCTD					1118:1121	standard synthetic peptide gCTD	1091:1121	standard synthetic peptide gCTD	1091:1121	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	0	56	theme	Labeling	63:70	arg1	Chemistry					91:99	Copper-Free Click Chemistry	73:99	Copper-Free Click Chemistry	73:99	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	0	56	theme	Labeling	63:70	arg1	Cleavage					112:119	Reductive Cleavage	102:119	Reductive Cleavage	102:119	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	0	56	theme	Labeling	63:70	arg1	Combination					33:43	a Combination	31:43	a Combination of Chemoenzymatic Labeling	31:70	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	0	56	theme	Labeling	63:70	arg1	Spectrometry					162:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	Electron-Transfer Dissociation Mass Spectrometry	126:173	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	5	57	theme	NeutrAvidin	882:892	arg1	beads					894:898	NeutrAvidin beads	882:898	NeutrAvidin beads	882:898	The tagged peptides were then released from NeutrAvidin beads upon reductant treatment, alkylated with (3-acrylamidopropyl)trimethylammonium chloride, and subjected to electron-transfer dissociation mass spectrometry analysis.
30657688	7	58	theme	important	1428:1436	arg1	proteins					1438:1445	important proteins	1428:1445	important proteins	1428:1445	Our method provides a promising tool for the site-specific characterization of O-GlcNAcylation of important proteins.
30657688	6	59	theme	model	1127:1131	arg1	α-crystallin					1141:1152	model protein α-crystallin	1127:1152	model protein α-crystallin	1127:1152	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	6	60	theme	binding	1253:1259	arg1	protein					1261:1267	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2	1207:1269	overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2)	1207:1276	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	6	60	theme	binding	1253:1259	arg1	TAB2					1272:1275	TAB2	1272:1275	TAB2	1272:1275	After validation by using standard synthetic peptide gCTD and model protein α-crystallin, such an approach was applied to the site mapping of overexpressed TGF-β-activated kinase 1/MAP3K7 binding protein 2 (TAB2), with four O-GlcNAc sites unambiguously identified.
30657688	0	61	theme	Chemoenzymatic	48:61	arg1	Labeling					63:70	Chemoenzymatic Labeling	48:70	Chemoenzymatic Labeling	48:70	O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.
30657688	7	62	theme	proteins	1438:1445	arg1	O-GlcNAcylation					1409:1423	O-GlcNAcylation	1409:1423	O-GlcNAcylation of important proteins	1409:1445	Our method provides a promising tool for the site-specific characterization of O-GlcNAcylation of important proteins.
30657688	3	63	theme	novel	552:556	arg1	method					558:563	a novel method	550:563	a novel method for O-GlcNAc enrichment and site mapping	550:604	Herein we present a novel method for O-GlcNAc enrichment and site mapping.
30231545	4	0	theme	C57BL/6	511:517	arg1	mice					519:522	Male C57BL/6 mice	506:522	Male C57BL/6 mice	506:522	Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined.
30231545	1	1	theme	biological	169:178	arg1	processes					180:188	many biological processes	164:188	many biological processes	164:188	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	10	2	theme	glycose	1784:1790	arg1	transport					1792:1800	glycose transport	1784:1800	glycose transport	1784:1800	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	6	3	theme	AKT	953:955	arg1	regulators					934:943	the glucose metabolism regulators	911:943	the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	911:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	3	theme	AKT	953:955	arg1	AS160					968:972	AS160	968:972	AS160	968:972	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	3	theme	AKT	953:955	arg1	substrate					957:965	160 kDa AKT substrate	945:965	160 kDa AKT substrate (AS160)	945:973	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	4	dep	regulators	934:943	arg1	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase					976:1026	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2	976:1028	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2)	976:1037	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	4	dep	regulators	934:943	arg1	synthase					1053:1060	glycogen synthase kinase-3β	1044:1070	glycogen synthase kinase-3β (GSK3β)	1044:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	4	dep	regulators	934:943	arg1	substrate					957:965	160 kDa AKT substrate	945:965	160 kDa AKT substrate (AS160)	945:973	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	4	dep	regulators	934:943	arg1	AS160					968:972	AS160	968:972	AS160	968:972	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	4	dep	regulators	934:943	arg1	PFKFB2					1031:1036	PFKFB2	1031:1036	PFKFB2	1031:1036	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	4	dep	regulators	934:943	arg1	regulators					934:943	the glucose metabolism regulators	911:943	the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	911:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	4	dep	regulators	934:943	arg1	GSK3β					1073:1077	GSK3β	1073:1077	GSK3β	1073:1077	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	9	5	theme	X	1402:1402	arg1	ratio					1410:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	6	6	theme	glycogen	1044:1051	arg1	regulators					934:943	the glucose metabolism regulators	911:943	the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	911:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	6	theme	glycogen	1044:1051	arg1	synthase					1053:1060	glycogen synthase kinase-3β	1044:1070	glycogen synthase kinase-3β (GSK3β)	1044:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	6	theme	glycogen	1044:1051	arg1	GSK3β					1073:1077	GSK3β	1073:1077	GSK3β	1073:1077	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	7	theme	kDa	949:951	arg1	regulators					934:943	the glucose metabolism regulators	911:943	the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	911:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	7	theme	kDa	949:951	arg1	AS160					968:972	AS160	968:972	AS160	968:972	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	7	theme	kDa	949:951	arg1	substrate					957:965	160 kDa AKT substrate	945:965	160 kDa AKT substrate (AS160)	945:973	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	3	8	theme	possible	373:380	arg1	effects					382:388	the possible effects	369:388	the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress	369:503	This study investigated the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress.
30231545	0	9	from	Effects	0:6	arg1	Glycometabolism					58:72	Glycometabolism	58:72	Glycometabolism	58:72	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	0	9	from	Effects	0:6	arg1	O-GlcNAcylation					38:52	Liver O-GlcNAcylation	32:52	Liver O-GlcNAcylation	32:52	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	10	10	theme	acute	1579:1583	arg1	stress					1590:1595	acute cold stress	1579:1595	acute cold stress	1579:1595	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	5	11	theme	phosphorylation	818:832	arg1	levels					834:839	global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels	768:839	global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels	768:839	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	9	12	theme	acid	1465:1468	arg1	caspase-3					1482:1490	cysteine-aspartic acid protease 3 (caspase-3)	1447:1491	cysteine-aspartic acid protease 3 (caspase-3)	1447:1491	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	6	13	theme	160	945:947	arg1	kDa					949:951	kDa	949:951	kDa	949:951	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	0	14	from	O-GlcNAcylation	38:52	arg1	Mice					77:80	Mice	77:80	Mice	77:80	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	4	15	theme	proteins	640:647	arg1	expression					626:635	the expression	622:635	the expression of proteins involved in glucose metabolism, apoptosis, and autophagy	622:704	Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined.
30231545	9	16	theme	B-cell	1360:1365	arg1	ratio					1410:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	4	17	theme	glucose	661:667	arg1	metabolism					669:678	glucose metabolism	661:678	glucose metabolism	661:678	Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined.
30231545	5	18	theme	O-GlcNAcylation	775:789	arg1	levels					834:839	global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels	768:839	global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels	768:839	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	5	19	theme	kinase	803:808	arg1	B					810:810	protein kinase B	795:810	protein kinase B (AKT)	795:816	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	5	19	theme	kinase	803:808	arg1	AKT					813:815	AKT	813:815	AKT	813:815	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	6	20	theme	regulators	934:943	arg1	levels					901:906	significantly increased activation levels	866:906	significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	866:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	4	21	theme	Male	506:509	arg1	mice					519:522	Male C57BL/6 mice	506:522	Male C57BL/6 mice	506:522	Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined.
30231545	7	22	theme	pyruvic	1156:1162	arg1	intermediates					1106:1118	glycolytic intermediates	1095:1118	glycolytic intermediates	1095:1118	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	7	22	theme	pyruvic	1156:1162	arg1	PA					1170:1171	PA	1170:1171	PA	1170:1171	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	7	22	theme	pyruvic	1156:1162	arg1	acid					1164:1167	pyruvic acid	1156:1167	pyruvic acid (PA)	1156:1172	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	5	23	theme	B	810:810	arg1	levels					834:839	global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels	768:839	global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels	768:839	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	5	24	theme	acute	740:744	arg1	stress					751:756	acute cold stress	740:756	acute cold stress	740:756	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	10	25	theme	cell	1754:1757	arg1	survival					1759:1766	cell survival	1754:1766	cell survival	1754:1766	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	10	26	theme	modification	1628:1639	arg1	levels					1641:1646	O-GlcNAc modification levels	1619:1646	O-GlcNAc modification levels	1619:1646	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	7	27	theme	brief	1196:1200	arg1	increase					1202:1209	a brief increase	1194:1209	a brief increase followed by a sharp decrease	1194:1238	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	9	28	theme	protease	1470:1477	arg1	caspase-3					1482:1490	cysteine-aspartic acid protease 3 (caspase-3)	1447:1491	cysteine-aspartic acid protease 3 (caspase-3)	1447:1491	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	5	29	theme	cold	746:749	arg1	stress					751:756	acute cold stress	740:756	acute cold stress	740:756	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	6	30	theme	metabolism	923:932	arg1	regulators					934:943	the glucose metabolism regulators	911:943	the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	911:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	30	theme	metabolism	923:932	arg1	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase					976:1026	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2	976:1028	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2)	976:1037	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	30	theme	metabolism	923:932	arg1	substrate					957:965	160 kDa AKT substrate	945:965	160 kDa AKT substrate (AS160)	945:973	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	30	theme	metabolism	923:932	arg1	synthase					1053:1060	glycogen synthase kinase-3β	1044:1070	glycogen synthase kinase-3β (GSK3β)	1044:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	9	31	theme	cysteine-aspartic	1447:1463	arg1	caspase-3					1482:1490	cysteine-aspartic acid protease 3 (caspase-3)	1447:1491	cysteine-aspartic acid protease 3 (caspase-3)	1447:1491	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	1	32	theme	Protein	83:89	arg1	O-GlcNAcylation					137:151	O-GlcNAcylation	137:151	O-GlcNAcylation	137:151	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	1	32	theme	Protein	83:89	arg1	glycosylation					122:134	Protein O-linked β-N-acetylglucosamine glycosylation	83:134	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	83:152	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	9	33	theme	Bax	1405:1407	arg1	ratio					1410:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	0	34	theme	Cold	17:20	arg1	Stress					22:27	Acute Cold Stress	11:27	Acute Cold Stress	11:27	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	6	35	theme	glucose	915:921	arg1	regulators					934:943	the glucose metabolism regulators	911:943	the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	911:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	35	theme	glucose	915:921	arg1	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase					976:1026	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2	976:1028	6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2)	976:1037	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	35	theme	glucose	915:921	arg1	substrate					957:965	160 kDa AKT substrate	945:965	160 kDa AKT substrate (AS160)	945:973	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	6	35	theme	glucose	915:921	arg1	synthase					1053:1060	glycogen synthase kinase-3β	1044:1070	glycogen synthase kinase-3β (GSK3β)	1044:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	9	36	theme	acute	1549:1553	arg1	stress					1560:1565	acute cold stress	1549:1565	acute cold stress	1549:1565	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	1	37	theme	O-linked	91:98	arg1	O-GlcNAcylation					137:151	O-GlcNAcylation	137:151	O-GlcNAcylation	137:151	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	1	37	theme	O-linked	91:98	arg1	glycosylation					122:134	Protein O-linked β-N-acetylglucosamine glycosylation	83:134	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	83:152	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	8	38	theme	energy	1306:1311	arg1	source					1313:1318	the main cellular energy source	1288:1318	the main cellular energy source	1288:1318	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	5	39	theme	global	768:773	arg1	O-GlcNAcylation					775:789	global O-GlcNAcylation	768:789	global O-GlcNAcylation	768:789	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	3	40	theme	O-GlcNAcylation	393:407	arg1	effects					382:388	the possible effects	369:388	the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress	369:503	This study investigated the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress.
30231545	9	41	theme	cold	1555:1558	arg1	stress					1560:1565	acute cold stress	1549:1565	acute cold stress	1549:1565	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	10	42	theme	processes	1706:1714	arg1	decrease					1680:1687	the decrease	1676:1687	the decrease of the essential processes of apoptosis and autophagy	1676:1741	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	1	43	theme	β-N-acetylglucosamine	100:120	arg1	O-GlcNAcylation					137:151	O-GlcNAcylation	137:151	O-GlcNAcylation	137:151	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	1	43	theme	β-N-acetylglucosamine	100:120	arg1	glycosylation					122:134	Protein O-linked β-N-acetylglucosamine glycosylation	83:134	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	83:152	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	3	44	theme	acute	487:491	arg1	stress					498:503	acute cold stress	487:503	acute cold stress	487:503	This study investigated the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress.
30231545	7	45	theme	glycolytic	1095:1104	arg1	acid					1164:1167	pyruvic acid	1156:1167	pyruvic acid (PA)	1156:1172	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	7	45	theme	glycolytic	1095:1104	arg1	fructose-1,6-diphosphate					1121:1144	fructose-1,6-diphosphate	1121:1144	fructose-1,6-diphosphate (FDP)	1121:1150	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	7	45	theme	glycolytic	1095:1104	arg1	intermediates					1106:1118	glycolytic intermediates	1095:1118	glycolytic intermediates	1095:1118	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	10	46	theme	O-GlcNAc	1619:1626	arg1	modification					1628:1639	O-GlcNAc modification	1619:1639	O-GlcNAc modification levels	1619:1646	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	10	47	theme	essential	1696:1704	arg1	processes					1706:1714	the essential processes	1692:1714	the essential processes of apoptosis and autophagy	1692:1741	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	2	48	theme	acute	264:268	arg1	stress					270:275	acute stress	264:275	acute stress	264:275	Studies have shown that O-GlcNAc modification levels can increase during acute stress and suggested that this may contribute to the survival of the cell.
30231545	0	49	theme	Stress	22:27	arg1	Effects					0:6	Effects	0:6	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice	0:80	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	4	50	theme	cold	540:543	arg1	conditions					545:554	cold conditions	540:554	cold conditions (4 °C)	540:561	Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined.
30231545	4	50	theme	cold	540:543	arg1	°C					559:560	4 °C	557:560	4 °C	557:560	Male C57BL/6 mice were exposed to cold conditions (4 °C) for 0, 2, 4, and 6 h, then their livers were extracted and the expression of proteins involved in glucose metabolism, apoptosis, and autophagy was determined.
30231545	7	51	theme	intermediates	1106:1118	arg1	levels					1085:1090	The levels	1081:1090	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA),	1081:1173	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	0	52	from	Glycometabolism	58:72	arg1	Mice					77:80	Mice	77:80	Mice	77:80	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	8	53	contain	had	1321:1323	arg2	increase					1333:1340	a sharp increase	1325:1340	a sharp increase	1325:1340	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	8	53	contain	had	1321:1323	arg1	ATP					1279:1281	ATP	1279:1281	ATP	1279:1281	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	8	53	contain	had	1321:1323	arg1	triphosphate					1265:1276	adenosine triphosphate	1255:1276	adenosine triphosphate (ATP)	1255:1282	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	5	54	theme	protein	795:801	arg1	B					810:810	protein kinase B	795:810	protein kinase B (AKT)	795:816	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	5	54	theme	protein	795:801	arg1	AKT					813:815	AKT	813:815	AKT	813:815	It was found that acute cold stress increased global O-GlcNAcylation and protein kinase B (AKT) phosphorylation levels.
30231545	3	55	theme	glucose	423:429	arg1	metabolism					431:440	glucose metabolism	423:440	glucose metabolism	423:440	This study investigated the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress.
30231545	6	56	theme	activation	890:899	arg1	levels					901:906	significantly increased activation levels	866:906	significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	866:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	10	57	theme	glycogen	1803:1810	arg1	synthesis					1812:1820	glycogen synthesis	1803:1820	glycogen synthesis	1803:1820	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	9	58	theme	Bcl-2	1378:1382	arg1	ratio					1410:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	0	59	theme	Liver	32:36	arg1	O-GlcNAcylation					38:52	Liver O-GlcNAcylation	32:52	Liver O-GlcNAcylation	32:52	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	6	60	theme	increased	880:888	arg1	levels					901:906	significantly increased activation levels	866:906	significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β)	866:1078	This was accompanied by significantly increased activation levels of the glucose metabolism regulators 160 kDa AKT substrate (AS160), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), and glycogen synthase kinase-3β (GSK3β).
30231545	10	61	theme	apoptosis	1719:1727	arg1	processes					1706:1714	the essential processes	1692:1714	the essential processes of apoptosis and autophagy	1692:1741	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	10	62	theme	autophagy	1733:1741	arg1	processes					1706:1714	the essential processes	1692:1714	the essential processes of apoptosis and autophagy	1692:1741	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	9	63	theme	caspase-3	1482:1490	arg1	levels					1523:1528	cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels	1447:1528	cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels	1447:1528	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	9	64	theme	lymphoma	1367:1374	arg1	ratio					1410:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	8	65	theme	sharp	1327:1331	arg1	increase					1333:1340	a sharp increase	1325:1340	a sharp increase	1325:1340	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	2	66	theme	modification	224:235	arg1	levels					237:242	O-GlcNAc modification levels	215:242	O-GlcNAc modification levels	215:242	Studies have shown that O-GlcNAc modification levels can increase during acute stress and suggested that this may contribute to the survival of the cell.
30231545	8	67	theme	cellular	1297:1304	arg1	source					1313:1318	the main cellular energy source	1288:1318	the main cellular energy source	1288:1318	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	3	68	theme	cold	493:496	arg1	stress					498:503	acute cold stress	487:503	acute cold stress	487:503	This study investigated the possible effects of O-GlcNAcylation that regulate glucose metabolism, apoptosis, and autophagy in the liver after acute cold stress.
30231545	8	69	theme	main	1292:1295	arg1	source					1313:1318	the main cellular energy source	1288:1318	the main cellular energy source	1288:1318	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	2	70	theme	O-GlcNAc	215:222	arg1	levels					237:242	O-GlcNAc modification levels	215:242	O-GlcNAc modification levels	215:242	Studies have shown that O-GlcNAc modification levels can increase during acute stress and suggested that this may contribute to the survival of the cell.
30231545	2	71	theme	cell	339:342	arg1	survival					323:330	the survival	319:330	the survival of the cell	319:342	Studies have shown that O-GlcNAc modification levels can increase during acute stress and suggested that this may contribute to the survival of the cell.
30231545	8	72	theme	adenosine	1255:1263	arg1	ATP					1279:1281	ATP	1279:1281	ATP	1279:1281	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	8	72	theme	adenosine	1255:1263	arg1	triphosphate					1265:1276	adenosine triphosphate	1255:1276	adenosine triphosphate (ATP)	1255:1282	Additionally, adenosine triphosphate (ATP), as the main cellular energy source, had a sharp increase.
30231545	9	73	theme	/Bcl-2-associated	1384:1400	arg1	ratio					1410:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio	1356:1414	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	1	74	link	O-linked	91:98	arg1	O-GlcNAcylation					137:151	O-GlcNAcylation	137:151	O-GlcNAcylation	137:151	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	1	74	link	O-linked	91:98	arg1	glycosylation					122:134	Protein O-linked β-N-acetylglucosamine glycosylation	83:134	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	83:152	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	9	75	theme	light	1497:1501	arg1	LC3-II					1515:1520	LC3-II	1515:1520	LC3-II	1515:1520	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	9	75	theme	light	1497:1501	arg1	chain					1503:1507	light chain 3-II	1497:1512	light chain 3-II (LC3-II)	1497:1521	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30231545	7	76	theme	sharp	1225:1229	arg1	decrease					1231:1238	a sharp decrease	1223:1238	a sharp decrease	1223:1238	The levels of glycolytic intermediates, fructose-1,6-diphosphate (FDP) and pyruvic acid (PA), were found to show a brief increase followed by a sharp decrease.
30231545	10	77	theme	cold	1585:1588	arg1	stress					1590:1595	acute cold stress	1579:1595	acute cold stress	1579:1595	Therefore, acute cold stress was found to increase O-GlcNAc modification levels, which may have resulted in the decrease of the essential processes of apoptosis and autophagy, promoting cell survival, while altering glycose transport, glycogen synthesis, and glycolysis in the liver.
30231545	0	78	theme	Acute	11:15	arg1	Stress					22:27	Acute Cold Stress	11:27	Acute Cold Stress	11:27	Effects of Acute Cold Stress on Liver O-GlcNAcylation and Glycometabolism in Mice.
30231545	1	79	theme	many	164:167	arg1	processes					180:188	many biological processes	164:188	many biological processes	164:188	Protein O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) regulates many biological processes.
30231545	9	80	theme	chain	1503:1507	arg1	levels					1523:1528	cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels	1447:1528	cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels	1447:1528	Furthermore, the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X (Bax) ratio was found to increase, whereas cysteine-aspartic acid protease 3 (caspase-3) and light chain 3-II (LC3-II) levels were reduced after acute cold stress.
30130254	5	0	theme	plasticity	570:579	arg1	target					498:503	proposed target	489:503	proposed target	489:503	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	0	theme	plasticity	570:579	arg1	program					581:587	a developmentally conserved epithelial plasticity program	531:587	a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT)	531:634	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	0	theme	plasticity	570:579	arg1	contributor					473:483	One contributor	469:483	One contributor	469:483	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	6	1	theme	mouse	675:679	arg1	models					681:686	novel autochthonous mouse models	655:686	novel autochthonous mouse models	655:686	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	8	2	theme	modification	1129:1140	arg1	levels					1052:1057	elevated levels	1043:1057	elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1043:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	7	3	theme	targeting	886:894	arg1	HBP					896:898	targeting HBP	886:898	targeting HBP	886:898	We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis.
30130254	6	4	theme	autochthonous	661:673	arg1	models					681:686	novel autochthonous mouse models	655:686	novel autochthonous mouse models	655:686	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	8	5	theme	HBP	1029:1031	arg1	downstream					1015:1024	downstream	1015:1024	downstream	1015:1024	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	6	6	theme	novel	655:659	arg1	models					681:686	novel autochthonous mouse models	655:686	novel autochthonous mouse models	655:686	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	11	7	theme	proteins	1358:1365	arg1	O-GlcNAcylation					1339:1353	O-GlcNAcylation	1339:1353	O-GlcNAcylation of proteins SNAI1 and c-MYC	1339:1381	O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis.
30130254	12	8	theme	plasticity	1612:1621	arg1	programs					1623:1630	epithelial plasticity programs	1601:1630	epithelial plasticity programs	1601:1630	Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.
30130254	8	9	theme	intracellular	1145:1157	arg1	proteins					1159:1166	intracellular proteins	1145:1166	intracellular proteins	1145:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	8	10	theme	β-N-acetylglucosamine	1071:1091	arg1	modification					1129:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification	1062:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1062:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	1	11	theme	Mutant	72:77	arg1	KRAS					79:82	Mutant KRAS	72:82	Mutant KRAS	72:82	Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation.
30130254	5	12	theme	KRAS-driven	508:518	arg1	cancers					520:526	KRAS-driven cancers	508:526	KRAS-driven cancers	508:526	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	3	13	theme	protein	348:354	arg1	N-					356:357	protein N-	348:357	protein N-	348:357	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	6	14	theme	enzymes	771:777	arg1	expression					753:762	expression	753:762	expression of key enzymes of the HBP pathway	753:796	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	8	15	theme	O-linked	1062:1069	arg1	modification					1129:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification	1062:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1062:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	5	16	theme	cancers	520:526	arg1	target					498:503	proposed target	489:503	proposed target	489:503	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	16	theme	cancers	520:526	arg1	program					581:587	a developmentally conserved epithelial plasticity program	531:587	a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT)	531:634	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	16	theme	cancers	520:526	arg1	contributor					473:483	One contributor	469:483	One contributor	469:483	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	8	17	theme	O-GlcNAcylation	1094:1108	arg1	modification					1129:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification	1062:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1062:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	11	18	theme	accelerated	1420:1430	arg1	tumorigenesis					1437:1449	accelerated lung tumorigenesis	1420:1449	accelerated lung tumorigenesis	1420:1449	O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis.
30130254	7	19	theme	KrasG12D-induced	853:868	arg1	senescence					870:879	KrasG12D-induced senescence	853:879	KrasG12D-induced senescence	853:879	We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis.
30130254	1	20	theme	glycolytic	91:100	arg1	flux					102:105	glycolytic flux	91:105	glycolytic flux in lung cancer	91:120	Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation.
30130254	7	21	theme	KrasG12D	922:929	arg1	tumorigenesis					936:948	KrasG12D lung tumorigenesis	922:948	KrasG12D lung tumorigenesis	922:948	We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis.
30130254	8	22	link	O-linked	1062:1069	arg1	modification					1129:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification	1062:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1062:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	8	23	from	proteins	1159:1166	arg1	levels					1052:1057	elevated levels	1043:1057	elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1043:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	8	24	theme	posttranslational	1111:1127	arg1	modification					1129:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification	1062:1140	O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1062:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	9	25	theme	lung	1255:1258	arg1	tumorigenesis					1260:1272	accelerated lung tumorigenesis	1243:1272	accelerated lung tumorigenesis	1243:1272	O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis.
30130254	11	26	dep	proteins	1358:1365	arg1	proteins					1358:1365	proteins SNAI1 and c-MYC	1358:1381	proteins SNAI1 and c-MYC	1358:1381	O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis.
30130254	11	26	dep	proteins	1358:1365	arg1	c-MYC					1377:1381	c-MYC	1377:1381	c-MYC	1377:1381	O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis.
30130254	11	26	dep	proteins	1358:1365	arg1	SNAI1					1367:1371	SNAI1	1367:1371	SNAI1	1367:1371	O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis.
30130254	5	27	theme	proposed	489:496	arg1	target					498:503	proposed target	489:503	proposed target	489:503	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	27	theme	proposed	489:496	arg1	program					581:587	a developmentally conserved epithelial plasticity program	531:587	a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT)	531:634	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	27	theme	proposed	489:496	arg1	contributor					473:483	One contributor	469:483	One contributor	469:483	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	12	28	theme	epithelial	1601:1610	arg1	programs					1623:1630	epithelial plasticity programs	1601:1630	epithelial plasticity programs	1601:1630	Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.
30130254	3	29	theme	glycolipid	382:391	arg1	synthesis					393:401	glycolipid synthesis	382:401	glycolipid synthesis	382:401	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	2	30	theme	aberrant	202:209	arg1	KRAS					211:214	aberrant KRAS	202:214	aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP)	202:284	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	1	31	theme	lung	110:113	arg1	cancer					115:120	lung cancer	110:120	lung cancer	110:120	Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation.
30130254	9	32	theme	accelerated	1243:1253	arg1	tumorigenesis					1260:1272	accelerated lung tumorigenesis	1243:1272	accelerated lung tumorigenesis	1243:1272	O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis.
30130254	0	33	theme	KRAS-induced	39:50	arg1	tumorigenesis					57:69	mutant KRAS-induced lung tumorigenesis	32:69	mutant KRAS-induced lung tumorigenesis	32:69	O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis.
30130254	6	34	theme	key	767:769	arg1	enzymes					771:777	key enzymes	767:777	key enzymes of the HBP pathway	767:796	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	2	35	theme	hexosamine	248:257	arg1	pathway					272:278	the hexosamine biosynthetic pathway	244:278	the hexosamine biosynthetic pathway (HBP)	244:284	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	2	35	theme	hexosamine	248:257	arg1	HBP					281:283	HBP	281:283	HBP	281:283	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	6	36	theme	lung	718:721	arg1	tumorigenesis					723:735	KrasG12D lung tumorigenesis	709:735	KrasG12D lung tumorigenesis	709:735	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	0	37	theme	mutant	32:37	arg1	tumorigenesis					57:69	mutant KRAS-induced lung tumorigenesis	32:69	mutant KRAS-induced lung tumorigenesis	32:69	O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis.
30130254	8	38	from	modification	1129:1140	arg1	proteins					1159:1166	intracellular proteins	1145:1166	intracellular proteins	1145:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	7	39	theme	lung	931:934	arg1	tumorigenesis					936:948	KrasG12D lung tumorigenesis	922:948	KrasG12D lung tumorigenesis	922:948	We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis.
30130254	6	40	theme	HBP	786:788	arg1	pathway					790:796	the HBP pathway	782:796	the HBP pathway	782:796	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	10	41	theme	O-GlcNAcylation	1295:1309	arg1	loss					1287:1290	loss	1287:1290	loss of O-GlcNAcylation	1287:1309	Conversely, loss of O-GlcNAcylation delayed lung tumorigenesis.
30130254	3	42	theme	various	307:313	arg1	N-					356:357	protein N-	348:357	protein N-	348:357	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	3	42	theme	various	307:313	arg1	processes					329:337	various glycosylation processes	307:337	various glycosylation processes	307:337	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	3	42	theme	various	307:313	arg1	O-glycosylation					362:376	O-glycosylation	362:376	O-glycosylation	362:376	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	2	43	theme	Recent	177:182	arg1	evidence					184:191	Recent evidence	177:191	Recent evidence	177:191	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	12	44	theme	lung	1549:1552	arg1	tumorigenesis					1554:1566	KrasG12D lung tumorigenesis	1540:1566	KrasG12D lung tumorigenesis	1540:1566	Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.
30130254	8	45	theme	protein	993:999	arg1	glycosylation					1001:1013	protein glycosylation	993:1013	protein glycosylation downstream of HBP	993:1031	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	0	46	theme	lung	52:55	arg1	tumorigenesis					57:69	mutant KRAS-induced lung tumorigenesis	32:69	mutant KRAS-induced lung tumorigenesis	32:69	O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis.
30130254	12	47	theme	KrasG12D	1540:1547	arg1	tumorigenesis					1554:1566	KrasG12D lung tumorigenesis	1540:1566	KrasG12D lung tumorigenesis	1540:1566	Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.
30130254	3	48	theme	glycosylation	315:327	arg1	N-					356:357	protein N-	348:357	protein N-	348:357	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	3	48	theme	glycosylation	315:327	arg1	processes					329:337	various glycosylation processes	307:337	various glycosylation processes	307:337	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	3	48	theme	glycosylation	315:327	arg1	O-glycosylation					362:376	O-glycosylation	362:376	O-glycosylation	362:376	HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis.
30130254	2	49	theme	glucose	231:237	arg1	flux					223:226	flux	223:226	flux of glucose into the hexosamine biosynthetic pathway (HBP)	223:284	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	5	50	theme	epithelial-mesenchymal	596:617	arg1	EMT					631:633	EMT	631:633	EMT	631:633	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	50	theme	epithelial-mesenchymal	596:617	arg1	transition					619:628	epithelial-mesenchymal transition	596:628	epithelial-mesenchymal transition (EMT)	596:634	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	11	51	theme	lung	1432:1435	arg1	tumorigenesis					1437:1449	accelerated lung tumorigenesis	1420:1449	accelerated lung tumorigenesis	1420:1449	O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis.
30130254	6	52	theme	KrasG12D	709:716	arg1	tumorigenesis					723:735	KrasG12D lung tumorigenesis	709:735	KrasG12D lung tumorigenesis	709:735	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	11	53	theme	EMT-HBP	1403:1409	arg1	axis					1411:1414	the EMT-HBP axis	1399:1414	the EMT-HBP axis	1399:1414	O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis.
30130254	8	54	theme	downstream	1015:1024	arg1	glycosylation					1001:1013	protein glycosylation	993:1013	protein glycosylation downstream of HBP	993:1031	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	8	55	theme	elevated	1043:1050	arg1	levels					1052:1057	elevated levels	1043:1057	elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins	1043:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	6	56	theme	pathway	790:796	arg1	enzymes					771:777	key enzymes	767:777	key enzymes of the HBP pathway	767:796	Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway.
30130254	8	57	from	levels	1052:1057	arg1	proteins					1159:1166	intracellular proteins	1145:1166	intracellular proteins	1145:1166	To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins.
30130254	2	58	dep	KRAS	211:214	arg1	drives					216:221	drives	216:221	drives flux of glucose into the hexosamine biosynthetic pathway (HBP)	216:284	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	9	59	theme	KrasG12D	1196:1203	arg1	OIS					1234:1236	OIS	1234:1236	OIS	1234:1236	O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis.
30130254	9	59	theme	KrasG12D	1196:1203	arg1	senescence					1222:1231	KrasG12D oncogene-induced senescence	1196:1231	KrasG12D oncogene-induced senescence (OIS)	1196:1237	O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis.
30130254	5	60	theme	conserved	549:557	arg1	target					498:503	proposed target	489:503	proposed target	489:503	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	60	theme	conserved	549:557	arg1	program					581:587	a developmentally conserved epithelial plasticity program	531:587	a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT)	531:634	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	60	theme	conserved	549:557	arg1	contributor					473:483	One contributor	469:483	One contributor	469:483	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	1	61	theme	aberrant	145:152	arg1	glycosylation					162:174	aberrant protein glycosylation	145:174	aberrant protein glycosylation	145:174	Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation.
30130254	1	62	from	flux	102:105	arg1	cancer					115:120	lung cancer	110:120	lung cancer	110:120	Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation.
30130254	2	63	theme	biosynthetic	259:270	arg1	pathway					272:278	the hexosamine biosynthetic pathway	244:278	the hexosamine biosynthetic pathway (HBP)	244:284	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	2	63	theme	biosynthetic	259:270	arg1	HBP					281:283	HBP	281:283	HBP	281:283	Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP).
30130254	5	64	theme	epithelial	559:568	arg1	target					498:503	proposed target	489:503	proposed target	489:503	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	64	theme	epithelial	559:568	arg1	program					581:587	a developmentally conserved epithelial plasticity program	531:587	a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT)	531:634	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	5	64	theme	epithelial	559:568	arg1	contributor					473:483	One contributor	469:483	One contributor	469:483	One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT).
30130254	1	65	theme	protein	154:160	arg1	glycosylation					162:174	aberrant protein glycosylation	145:174	aberrant protein glycosylation	145:174	Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation.
30130254	9	66	theme	oncogene-induced	1205:1220	arg1	OIS					1234:1236	OIS	1234:1236	OIS	1234:1236	O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis.
30130254	9	66	theme	oncogene-induced	1205:1220	arg1	senescence					1222:1231	KrasG12D oncogene-induced senescence	1196:1231	KrasG12D oncogene-induced senescence (OIS)	1196:1237	O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis.
30130254	10	67	theme	lung	1319:1322	arg1	tumorigenesis					1324:1336	lung tumorigenesis	1319:1336	lung tumorigenesis	1319:1336	Conversely, loss of O-GlcNAcylation delayed lung tumorigenesis.
29121919	10	0	from	animals	1578:1584	arg1	hearts					1566:1571	hearts	1566:1571	hearts from animals with diabetes (p < 0.05)	1566:1609	During hypoglycemia, however, IPC only reduced IS in hearts from animals with diabetes (p < 0.05).
29121919	14	1	theme	MGU	2267:2269	arg1	levels					2284:2289	increased MGU and O-GlcNAc levels	2257:2289	increased MGU and O-GlcNAc levels	2257:2289	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	13	2	dep	hearts	2031:2036	arg1	contrast					2019:2026	contrast	2019:2026	contrast	2019:2026	In contrast to hearts from animals without diabetes, the hearts from animals with diabetes are amenable to cardioprotection during hypoglycemia.
29121919	3	3	theme	O-linked	558:565	arg1	O-GlcNAc					590:597	O-GlcNAc	590:597	O-GlcNAc	590:597	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	3	theme	O-linked	558:565	arg1	β-N-acetylglucosamine					567:587	O-linked β-N-acetylglucosamine	558:587	O-linked β-N-acetylglucosamine (O-GlcNAc)	558:598	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	11	4	dep	MGU	1856:1858	arg1	p < 0.05					1861:1868	p < 0.05	1861:1868	p < 0.05	1861:1868	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	11	4	dep	MGU	1856:1858	arg1	p < 0.01					1881:1888	p < 0.01	1881:1888	p < 0.01	1881:1888	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	11	4	dep	MGU	1856:1858	arg1	O-GlcNAc					1871:1878	O-GlcNAc	1871:1878	O-GlcNAc	1871:1878	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	2	5	theme	reduced	291:297	arg1	tolerance					310:318	myocardial tolerance	299:318	myocardial tolerance to ischemia and reperfusion (IR)	299:351	The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC).
29121919	10	6	with	animals	1578:1584	arg1	p < 0.05					1601:1608	p < 0.05	1601:1608	p < 0.05	1601:1608	During hypoglycemia, however, IPC only reduced IS in hearts from animals with diabetes (p < 0.05).
29121919	10	6	with	animals	1578:1584	arg1	diabetes					1591:1598	diabetes	1591:1598	diabetes (p < 0.05)	1591:1609	During hypoglycemia, however, IPC only reduced IS in hearts from animals with diabetes (p < 0.05).
29121919	9	7	from	normoglycemia	1434:1446	arg1	animals					1456:1462	both animals	1451:1462	both animals with (p < 0.01) and without (p < 0.01) diabetes	1451:1510	IPC reduced IS during normoglycemia in both animals with (p < 0.01) and without (p < 0.01) diabetes.
29121919	14	8	theme	O-GlcNAc	2216:2223	arg1	levels					2225:2230	MGU and O-GlcNAc levels	2208:2230	MGU and O-GlcNAc levels	2208:2230	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	1	9	theme	increased	201:209	arg1	rate					221:224	increased mortality rate	201:224	increased mortality rate in patients with diabetes	201:250	BACKGROUND Hypoglycemia is associated with increased mortality rate in patients with diabetes.
29121919	11	10	from	levels	1662:1667	arg1	animals					1672:1678	animals	1672:1678	animals with diabetes	1672:1692	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	5	11	from	METHODS	834:840	arg1	model					859:863	a Langendorff model	845:863	a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS)	845:961	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	5	12	theme	120	1013:1015	arg1	min					1017:1019	min	1017:1019	min	1017:1019	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	8	13	dep	increased	1284:1292	arg1	compared					1385:1392	compared	1385:1392	compared to normoglycemia	1385:1409	RESULTS IS increased in hearts from animals with (p < 0.01) and without (p < 0.01) diabetes during hypoglycemia compared to normoglycemia.
29121919	0	14	from	preconditioning	88:102	arg1	rats					119:122	rats	119:122	rats with and without type 2 diabetes	119:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	0	14	from	preconditioning	88:102	arg1	hearts					107:112	hearts	107:112	hearts from rats with and without type 2 diabetes	107:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	5	15	dep	size	953:956	arg1	IS					959:960	IS	959:960	IS	959:960	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	0	16	theme	type	141:144	arg1	diabetes					148:155	type 2 diabetes	141:155	type 2 diabetes	141:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	5	17	theme	reperfusion	1021:1031	arg1	40 min					983:988	40 min	983:988	40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l]	983:1116	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	5	18	theme	Langendorff	847:857	arg1	model					859:863	a Langendorff model	845:863	a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS)	845:961	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	0	19	from	injury	77:82	arg1	rats					119:122	rats	119:122	rats with and without type 2 diabetes	119:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	0	19	from	injury	77:82	arg1	hearts					107:112	hearts	107:112	hearts from rats with and without type 2 diabetes	107:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	11	20	with	animals	1672:1678	arg1	diabetes					1685:1692	diabetes	1685:1692	diabetes	1685:1692	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	0	21	from	rats	119:122	arg1	preconditioning					88:102	preconditioning	88:102	preconditioning	88:102	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	0	21	from	rats	119:122	arg1	injury					77:82	ischemia-reperfusion injury	56:82	ischemia-reperfusion injury	56:82	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	0	21	from	rats	119:122	arg1	hearts					107:112	hearts	107:112	hearts from rats with and without type 2 diabetes	107:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	12	22	theme	IR	1956:1957	arg1	injury					1959:1964	IR injury	1956:1964	IR injury	1956:1964	CONCLUSIONS Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes.
29121919	5	23	theme	non-diabetic	896:907	arg1	rats					916:919	diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats	871:919	rats	916:919	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	6	24	theme	glucose	1130:1136	arg1	uptake					1138:1143	Myocardial glucose uptake	1119:1143	Myocardial glucose uptake	1119:1143	Myocardial glucose uptake and O-GlcNAc levels were evaluated during reperfusion.
29121919	12	25	theme	CONCLUSIONS	1892:1902	arg1	Hypoglycemia					1904:1915	CONCLUSIONS Hypoglycemia	1892:1915	CONCLUSIONS Hypoglycemia	1892:1915	CONCLUSIONS Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes.
29121919	14	26	theme	induced	2182:2188	arg1	cardioprotection					2190:2205	IPC induced cardioprotection	2178:2205	IPC induced cardioprotection	2178:2205	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	4	27	from	impact	629:634	arg1	hearts					655:660	hearts	655:660	hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms	655:831	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	4	27	from	impact	629:634	arg1	animals					667:673	animals	667:673	animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms	667:831	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	2	28	theme	underlying	257:266	arg1	mechanisms					268:277	The underlying mechanisms	253:277	The underlying mechanisms	253:277	The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC).
29121919	9	29	with	animals	1456:1462	arg1	p < 0.01					1470:1477	(p < 0.01)	1469:1478	(p < 0.01)	1469:1478	IPC reduced IS during normoglycemia in both animals with (p < 0.01) and without (p < 0.01) diabetes.
29121919	11	30	dep	hypo-	1701:1705	arg1	O-GlcNAc					1723:1730	O-GlcNAc	1723:1730	O-GlcNAc	1723:1730	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	11	30	dep	hypo-	1701:1705	arg1	MGU					1708:1710	MGU	1708:1710	MGU	1708:1710	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	5	31	theme	ischemia	1000:1007	arg1	40 min					983:988	40 min	983:988	40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l]	983:1116	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	0	32	from	Effects	0:6	arg1	susceptibility					38:51	myocardial susceptibility	27:51	myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes	27:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	4	33	theme	MGU	767:769	arg1	levels					784:789	MGU and O-GlcNAc levels	767:789	MGU and O-GlcNAc levels	767:789	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	11	34	dep	MGU	1708:1710	arg1	p < 0.05					1733:1740	p < 0.05	1733:1740	p < 0.05	1733:1740	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	11	34	dep	MGU	1708:1710	arg1	p < 0.05					1713:1720	p < 0.05	1713:1720	p < 0.05	1713:1720	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	12	35	from	susceptibility	1938:1951	arg1	hearts					1969:1974	hearts	1969:1974	hearts from animals with and without diabetes	1969:2013	CONCLUSIONS Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes.
29121919	12	35	from	susceptibility	1938:1951	arg1	animals					1981:1987	animals	1981:1987	animals with and without diabetes	1981:2013	CONCLUSIONS Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes.
29121919	13	36	from	animals	2085:2091	arg1	amenable					2111:2118	amenable	2111:2118	amenable	2111:2118	In contrast to hearts from animals without diabetes, the hearts from animals with diabetes are amenable to cardioprotection during hypoglycemia.
29121919	13	36	from	animals	2085:2091	arg1	hearts					2073:2078	the hearts	2069:2078	the hearts from animals with diabetes	2069:2105	In contrast to hearts from animals without diabetes, the hearts from animals with diabetes are amenable to cardioprotection during hypoglycemia.
29121919	4	37	theme	O-GlcNAc	775:782	arg1	levels					784:789	MGU and O-GlcNAc levels	767:789	MGU and O-GlcNAc levels	767:789	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	3	38	theme	myocardial	445:454	arg1	MGU					472:474	MGU	472:474	MGU	472:474	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	38	theme	myocardial	445:454	arg1	uptake					464:469	increased myocardial glucose uptake	435:469	increased myocardial glucose uptake (MGU) during reperfusion	435:494	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	5	39	theme	infarct	945:951	arg1	size					953:956	infarct size	945:956	diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS)	871:961	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	11	40	dep	normoglycemia	1747:1759	arg1	MGU					1762:1764	MGU	1762:1764	MGU	1762:1764	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	7	41	theme	index	1257:1261	arg1	ischemia					1263:1270	index ischemia	1257:1270	index ischemia	1257:1270	IPC was induced by 2 × 5 min of global ischemia prior to index ischemia.
29121919	0	42	theme	hypoglycemia	11:22	arg1	Effects					0:6	Effects	0:6	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes	0:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	1	43	with	patients	229:236	arg1	diabetes					243:250	diabetes	243:250	diabetes	243:250	BACKGROUND Hypoglycemia is associated with increased mortality rate in patients with diabetes.
29121919	11	44	dep	MGU	1762:1764	arg1	O-GlcNAc					1777:1784	O-GlcNAc	1777:1784	O-GlcNAc: p < 0.05	1777:1794	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	11	44	dep	MGU	1762:1764	arg1	p < 0.01					1767:1774	p < 0.01	1767:1774	p < 0.01	1767:1774	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	4	45	theme	IR	703:704	arg1	tolerance					706:714	myocardial IR tolerance	692:714	myocardial IR tolerance	692:714	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	4	46	theme	underlying	811:820	arg1	mechanisms					822:831	the underlying mechanisms	807:831	the underlying mechanisms	807:831	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	0	47	theme	myocardial	27:36	arg1	susceptibility					38:51	myocardial susceptibility	27:51	myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes	27:155	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	7	48	theme	global	1232:1237	arg1	ischemia					1239:1246	global ischemia	1232:1246	global ischemia	1232:1246	IPC was induced by 2 × 5 min of global ischemia prior to index ischemia.
29121919	4	49	with	animals	667:673	arg1	diabetes					680:687	diabetes	680:687	diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms	680:831	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	2	50	theme	reduced	356:362	arg1	capacity					364:371	reduced capacity	356:371	reduced capacity for ischemic preconditioning (IPC)	356:406	The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC).
29121919	11	51	dep	O-GlcNAc	1777:1784	arg1	p < 0.05					1787:1794	p < 0.05	1787:1794	p < 0.05	1787:1794	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	3	52	attach	linked	517:522	arg3	β-N-acetylglucosamine					567:587	O-linked β-N-acetylglucosamine	558:587	O-linked β-N-acetylglucosamine (O-GlcNAc)	558:598	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	52	attach	linked	517:522	arg1	metabolism					535:544	glucose metabolism	527:544	glucose metabolism	527:544	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	52	attach	linked	517:522	arg2	cardioprotection					497:512	cardioprotection	497:512	cardioprotection	497:512	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	52	attach	linked	517:522	arg3	O-GlcNAc					590:597	O-GlcNAc	590:597	O-GlcNAc	590:597	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	8	53	from	animals	1309:1315	arg1	hearts					1297:1302	hearts	1297:1302	hearts from animals with (p < 0.01) and without (p < 0.01) diabetes during hypoglycemia	1297:1383	RESULTS IS increased in hearts from animals with (p < 0.01) and without (p < 0.01) diabetes during hypoglycemia compared to normoglycemia.
29121919	14	54	with	parallel	2164:2171	arg1	cardioprotection					2190:2205	IPC induced cardioprotection	2178:2205	IPC induced cardioprotection	2178:2205	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	14	55	theme	increased	2257:2265	arg1	levels					2284:2289	increased MGU and O-GlcNAc levels	2257:2289	increased MGU and O-GlcNAc levels	2257:2289	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	11	56	dep	increased	1616:1624	arg1	MGU					1856:1858	MGU	1856:1858	MGU	1856:1858	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	2	57	theme	myocardial	299:308	arg1	tolerance					310:318	myocardial tolerance	299:318	myocardial tolerance to ischemia and reperfusion (IR)	299:351	The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC).
29121919	4	58	from	diabetes	680:687	arg1	tolerance					706:714	myocardial IR tolerance	692:714	myocardial IR tolerance	692:714	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	4	58	from	diabetes	680:687	arg1	efficacy					724:731	the efficacy	720:731	the efficacy of IPC	720:738	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	14	59	theme	IPC	2325:2327	arg1	mechanisms					2311:2320	the mechanisms	2307:2320	the mechanisms of IPC	2307:2327	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	13	60	with	animals	2085:2091	arg1	diabetes					2098:2105	diabetes	2098:2105	diabetes	2098:2105	In contrast to hearts from animals without diabetes, the hearts from animals with diabetes are amenable to cardioprotection during hypoglycemia.
29121919	4	61	from	animals	667:673	arg1	hearts					655:660	hearts	655:660	hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms	655:831	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	4	61	from	animals	667:673	arg1	impact					629:634	the impact	625:634	the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms	625:831	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	5	62	theme	diabetic	871:878	arg1	fa/fa					885:889	diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats	871:919	fa/fa	885:889	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	1	63	theme	mortality	211:219	arg1	rate					221:224	increased mortality rate	201:224	increased mortality rate in patients with diabetes	201:250	BACKGROUND Hypoglycemia is associated with increased mortality rate in patients with diabetes.
29121919	4	64	theme	hypoglycemia	639:650	arg1	impact					629:634	the impact	625:634	the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms	625:831	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	5	65	theme	min	1017:1019	arg1	reperfusion					1021:1031	120 min reperfusion	1013:1031	120 min reperfusion	1013:1031	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	5	66	theme	ZDF	880:882	arg1	fa/fa					885:889	diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats	871:919	fa/fa	885:889	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	9	67	theme	reduced	1416:1422	arg1	IPC					1412:1414	IPC reduced	1412:1422	IPC reduced	1412:1422	IPC reduced IS during normoglycemia in both animals with (p < 0.01) and without (p < 0.01) diabetes.
29121919	6	68	theme	O-GlcNAc	1149:1156	arg1	levels					1158:1163	O-GlcNAc levels	1149:1163	O-GlcNAc levels	1149:1163	Myocardial glucose uptake and O-GlcNAc levels were evaluated during reperfusion.
29121919	12	69	theme	myocardial	1927:1936	arg1	susceptibility					1938:1951	myocardial susceptibility	1927:1951	myocardial susceptibility to IR injury in hearts from animals with and without diabetes	1927:2013	CONCLUSIONS Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes.
29121919	14	70	theme	MGU	2208:2210	arg1	levels					2225:2230	MGU and O-GlcNAc levels	2208:2230	MGU and O-GlcNAc levels	2208:2230	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	5	71	theme	global	993:998	arg1	ischemia					1000:1007	global ischemia	993:1007	global ischemia	993:1007	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	1	72	from	rate	221:224	arg1	patients					229:236	patients	229:236	patients with diabetes	229:250	BACKGROUND Hypoglycemia is associated with increased mortality rate in patients with diabetes.
29121919	5	73	theme	fa/+	910:913	arg1	rats					916:919	diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats	871:919	rats	916:919	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	11	74	theme	O-GlcNAc	1653:1660	arg1	levels					1662:1667	O-GlcNAc levels	1653:1667	O-GlcNAc levels in animals with diabetes	1653:1692	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	6	75	theme	Myocardial	1119:1128	arg1	uptake					1138:1143	Myocardial glucose uptake	1119:1143	Myocardial glucose uptake	1119:1143	Myocardial glucose uptake and O-GlcNAc levels were evaluated during reperfusion.
29121919	4	76	theme	myocardial	692:701	arg1	tolerance					706:714	myocardial IR tolerance	692:714	myocardial IR tolerance	692:714	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	14	77	theme	IPC	2178:2180	arg1	cardioprotection					2190:2205	IPC induced cardioprotection	2178:2205	IPC induced cardioprotection	2178:2205	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	1	78	theme	BACKGROUND	158:167	arg1	Hypoglycemia					169:180	BACKGROUND Hypoglycemia	158:180	BACKGROUND Hypoglycemia	158:180	BACKGROUND Hypoglycemia is associated with increased mortality rate in patients with diabetes.
29121919	11	79	from	MGU	1626:1628	arg1	animals					1672:1678	animals	1672:1678	animals with diabetes	1672:1692	IPC increased MGU during reperfusion and O-GlcNAc levels in animals with diabetes during hypo- (MGU: p < 0.05, O-GlcNAc: p < 0.05) and normoglycemia (MGU: p < 0.01, O-GlcNAc: p < 0.05) and in animals without diabetes only during normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01).
29121919	8	80	with	animals	1309:1315	arg1	p < 0.01					1323:1330	(p < 0.01)	1322:1331	(p < 0.01)	1322:1331	RESULTS IS increased in hearts from animals with (p < 0.01) and without (p < 0.01) diabetes during hypoglycemia compared to normoglycemia.
29121919	12	81	from	animals	1981:1987	arg1	hearts					1969:1974	hearts	1969:1974	hearts from animals with and without diabetes	1969:2013	CONCLUSIONS Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes.
29121919	12	81	from	animals	1981:1987	arg1	susceptibility					1938:1951	myocardial susceptibility	1927:1951	myocardial susceptibility to IR injury in hearts from animals with and without diabetes	1927:2013	CONCLUSIONS Hypoglycemia increases myocardial susceptibility to IR injury in hearts from animals with and without diabetes.
29121919	3	82	link	O-linked	558:565	arg1	O-GlcNAc					590:597	O-GlcNAc	590:597	O-GlcNAc	590:597	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	82	link	O-linked	558:565	arg1	β-N-acetylglucosamine					567:587	O-linked β-N-acetylglucosamine	558:587	O-linked β-N-acetylglucosamine (O-GlcNAc)	558:598	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	83	theme	glucose	456:462	arg1	MGU					472:474	MGU	472:474	MGU	472:474	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	83	theme	glucose	456:462	arg1	uptake					464:469	increased myocardial glucose uptake	435:469	increased myocardial glucose uptake (MGU) during reperfusion	435:494	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	5	84	theme	glucose	1055:1061	arg1	 = 3 mmol/l					1063:1073	(glucose) = 3 mmol/l	1054:1073	(glucose) = 3 mmol/l	1054:1073	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	5	84	theme	glucose	1055:1061	arg1	hypoglycemia					1040:1051	hypoglycemia	1040:1051	hypoglycemia [(glucose) = 3 mmol/l]	1040:1074	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	4	85	theme	IPC	736:738	arg1	efficacy					724:731	the efficacy	720:731	the efficacy of IPC	720:738	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	3	86	theme	increased	435:443	arg1	MGU					472:474	MGU	472:474	MGU	472:474	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	3	86	theme	increased	435:443	arg1	uptake					464:469	increased myocardial glucose uptake	435:469	increased myocardial glucose uptake (MGU) during reperfusion	435:494	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	5	87	from	fa/fa	885:889	arg1	group					938:942	each group	933:942	each group	933:942	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	7	88	theme	ischemia	1239:1246	arg1	2 × 5 min					1219:1227	2 × 5 min	1219:1227	2 × 5 min of global ischemia	1219:1246	IPC was induced by 2 × 5 min of global ischemia prior to index ischemia.
29121919	5	89	dep	fa/fa	885:889	arg1	n = 6-7					922:928	n = 6-7	922:928	n = 6-7	922:928	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	5	89	dep	fa/fa	885:889	arg1	size					953:956	infarct size	945:956	diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS)	871:961	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	0	90	theme	ischemia-reperfusion	56:75	arg1	injury					77:82	ischemia-reperfusion injury	56:82	ischemia-reperfusion injury	56:82	Effects of hypoglycemia on myocardial susceptibility to ischemia-reperfusion injury and preconditioning in hearts from rats with and without type 2 diabetes.
29121919	13	91	from	animals	2043:2049	arg1	hearts					2031:2036	hearts	2031:2036	hearts from animals without diabetes	2031:2066	In contrast to hearts from animals without diabetes, the hearts from animals with diabetes are amenable to cardioprotection during hypoglycemia.
29121919	5	92	theme	glucose	1096:1102	arg1	 = 11 mmol/l					1104:1115	(glucose) = 11 mmol/l	1095:1115	(glucose) = 11 mmol/l	1095:1115	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	5	92	theme	glucose	1096:1102	arg1	normoglycemia					1080:1092	normoglycemia	1080:1092	normoglycemia [(glucose) = 11 mmol/l]	1080:1116	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	4	93	theme	levels	784:789	arg1	modulations					752:762	modulations	752:762	modulations of MGU and O-GlcNAc levels	752:789	We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms.
29121919	3	94	theme	glucose	527:533	arg1	metabolism					535:544	glucose metabolism	527:544	glucose metabolism	527:544	As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc).
29121919	5	95	from	rats	916:919	arg1	group					938:942	each group	933:942	each group	933:942	METHODS In a Langendorff model using diabetic ZDF (fa/fa) and non-diabetic (fa/+) rats (n = 6-7 in each group) infarct size (IS) was evaluated after 40 min of global ischemia and 120 min reperfusion during hypoglycemia [(glucose) = 3 mmol/l] and normoglycemia [(glucose) = 11 mmol/l].
29121919	14	96	theme	O-GlcNAc	2275:2282	arg1	levels					2284:2289	increased MGU and O-GlcNAc levels	2257:2289	increased MGU and O-GlcNAc levels	2257:2289	In parallel with IPC induced cardioprotection, MGU and O-GlcNAc levels increase suggesting that increased MGU and O-GlcNAc levels are involved in the mechanisms of IPC.
29121919	2	97	theme	ischemic	377:384	arg1	IPC					403:405	IPC	403:405	IPC	403:405	The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC).
29121919	2	97	theme	ischemic	377:384	arg1	preconditioning					386:400	ischemic preconditioning	377:400	ischemic preconditioning (IPC)	377:406	The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC).
28542923	0	0	theme	neurite	87:93	arg1	outgrowth					95:103	neurite outgrowth	87:103	neurite outgrowth	87:103	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	6	1	theme	cerebellar	1344:1353	arg1	neurons					1355:1361	cultured cerebellar neurons	1335:1361	cultured cerebellar neurons	1335:1361	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	4	2	theme	novel	814:818	arg1	mimetics					835:842	novel small molecule mimetics	814:842	novel small molecule mimetics of PSA that are applicable for therapy	814:881	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	6	3	theme	similar	1423:1429	arg1	manner					1431:1436	a similar manner	1421:1436	a similar manner as colominic acid	1421:1454	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	3	4	theme	nervous	777:783	arg1	system					785:790	nervous system	777:790	nervous system injury	777:797	In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury.
28542923	2	5	theme	axon	505:508	arg1	migration					494:502	cell migration	489:502	cell migration	489:502	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	5	theme	axon	505:508	arg1	pathfinding					510:520	axon pathfinding	505:520	axon pathfinding	505:520	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	1	6	theme	O-linked	324:331	arg1	glycans					333:339	O-linked glycans	324:339	O-linked glycans	324:339	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	2	7	dep	controls	412:419	arg1	enhancing					479:487	enhancing	479:487	enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity	479:561	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	7	dep	controls	412:419	arg1	regulating					567:576	regulating	567:576	regulating the differentiation of progenitor cells	567:616	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	7	dep	controls	412:419	arg1	modulating					625:634	modulating	625:634	modulating cell-cell and cell-matrix adhesions	625:670	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	7	8	theme	nervous	1859:1865	arg1	system					1867:1872	nervous system	1859:1872	nervous system injuries	1859:1881	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	2	9	theme	synaptic	543:550	arg1	migration					494:502	cell migration	489:502	cell migration	489:502	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	9	theme	synaptic	543:550	arg1	plasticity					552:561	synaptic plasticity	543:561	synaptic plasticity	543:561	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	4	10	theme	inhibitor	1006:1014	arg1	class					1016:1020	the topoisomerase I inhibitor class	986:1020	the topoisomerase I inhibitor class	986:1020	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	3	11	theme	system	785:790	arg1	injury					792:797	nervous system injury	777:797	nervous system injury	777:797	In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury.
28542923	2	12	theme	cell	489:492	arg1	migration					494:502	cell migration	489:502	cell migration	489:502	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	12	theme	cell	489:492	arg1	pathfinding					510:520	axon pathfinding	505:520	axon pathfinding	505:520	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	12	theme	cell	489:492	arg1	targeting					532:540	synaptic targeting	523:540	synaptic targeting	523:540	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	12	theme	cell	489:492	arg1	plasticity					552:561	synaptic plasticity	543:561	synaptic plasticity	543:561	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	6	13	theme	irinotecan-stimulated	1562:1582	arg1	outgrowth					1592:1600	irinotecan-stimulated neurite outgrowth	1562:1600	irinotecan-stimulated neurite outgrowth	1562:1600	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	4	14	theme	molecule	826:833	arg1	mimetics					835:842	novel small molecule mimetics	814:842	novel small molecule mimetics of PSA that are applicable for therapy	814:881	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	2	15	theme	cells	612:616	arg1	differentiation					582:596	the differentiation	578:596	the differentiation of progenitor cells	578:616	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	4	16	theme	antineoplastic	913:926	arg1	idarubicin					898:907	idarubicin	898:907	idarubicin	898:907	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	16	theme	antineoplastic	913:926	arg1	anthracycline					928:940	an antineoplastic anthracycline	910:940	an antineoplastic anthracycline	910:940	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	0	17	theme	large	165:169	arg1	homopolymer					199:209	a large, negatively charged, linear homopolymer	163:209	a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues	163:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	17	theme	large	165:169	arg1	acid					149:152	C. Polysialic acid	135:152	C. Polysialic acid (PSA)	135:158	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	18	theme	sialic	230:235	arg1	residues					242:249	alpha2-8-linked sialic acid residues	214:249	alpha2-8-linked sialic acid residues	214:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	4	19	theme	immunosorbent	1073:1085	arg1	assay					1087:1091	a competition enzyme-linked immunosorbent assay	1045:1091	a competition enzyme-linked immunosorbent assay	1045:1091	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	2	20	dep	development	425:435	arg1	the					421:423	the	421:423	the	421:423	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	0	21	theme	alpha2-8-linked	214:228	arg1	residues					242:249	alpha2-8-linked sialic acid residues	214:249	alpha2-8-linked sialic acid residues	214:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	4	22	theme	enzyme-linked	1059:1071	arg1	assay					1087:1091	a competition enzyme-linked immunosorbent assay	1045:1091	a competition enzyme-linked immunosorbent assay	1045:1091	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	2	23	theme	system	469:474	arg1	regeneration					441:452	regeneration	441:452	regeneration	441:452	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	23	theme	system	469:474	arg1	development					425:435	development	425:435	development	425:435	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	7	24	theme	signaling	1763:1771	arg1	cascades					1773:1780	the same signaling cascades	1754:1780	the same signaling cascades as PSA	1754:1787	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	0	25	theme	residues	242:249	arg1	homopolymer					199:209	a large, negatively charged, linear homopolymer	163:209	a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues	163:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	25	theme	residues	242:249	arg1	acid					149:152	C. Polysialic acid	135:152	C. Polysialic acid (PSA)	135:158	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	5	26	theme	bacterial	1183:1191	arg1	analog					1193:1198	the bacterial analog	1179:1198	the bacterial analog of PSA	1179:1205	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	5	26	theme	bacterial	1183:1191	arg1	peptide					1151:1157	the PSA-mimicking peptide	1133:1157	the PSA-mimicking peptide	1133:1157	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	0	27	theme	polysialic	4:13	arg1	mimetics					20:27	The polysialic acid mimetics	0:27	The polysialic acid mimetics idarubicin and irinotecan	0:53	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	27	theme	polysialic	4:13	arg1	irinotecan					44:53	irinotecan	44:53	irinotecan	44:53	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	27	theme	polysialic	4:13	arg1	idarubicin					29:38	idarubicin	29:38	idarubicin	29:38	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	1	28	theme	main	350:353	arg1	carrier					355:361	its main carrier	346:361	its main carrier	346:361	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	28	theme	main	350:353	arg1	molecule					391:398	the neural cell adhesion molecule	366:398	the neural cell adhesion molecule (NCAM)	366:405	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	7	29	theme	system	1867:1872	arg1	injuries					1874:1881	nervous system injuries	1859:1881	nervous system injuries	1859:1881	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	0	30	theme	acid	237:240	arg1	residues					242:249	alpha2-8-linked sialic acid residues	214:249	alpha2-8-linked sialic acid residues	214:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	31	link	alpha2-8-linked	214:228	arg1	residues					242:249	alpha2-8-linked sialic acid residues	214:249	alpha2-8-linked sialic acid residues	214:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	2	32	theme	cell-cell	636:644	arg1	adhesions					662:670	cell-cell and cell-matrix adhesions	636:670	cell-cell and cell-matrix adhesions	636:670	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	1	33	link	O-linked	324:331	arg1	glycans					333:339	O-linked glycans	324:339	O-linked glycans	324:339	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	6	34	theme	tensin	1511:1516	arg1	homolog					1518:1524	tensin homolog	1511:1524	tensin homolog	1511:1524	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	7	35	theme	novel	1609:1613	arg1	results					1615:1621	These novel results	1603:1621	These novel results	1603:1621	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	6	36	theme	neurite	1301:1307	arg1	outgrowth					1309:1317	neurite outgrowth	1301:1317	neurite outgrowth	1301:1317	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	2	37	theme	progenitor	601:610	arg1	cells					612:616	progenitor cells	601:616	progenitor cells	601:616	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	6	38	theme	cultured	1335:1342	arg1	neurons					1355:1361	cultured cerebellar neurons	1335:1361	cultured cerebellar neurons	1335:1361	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	0	39	theme	acid	15:18	arg1	mimetics					20:27	The polysialic acid mimetics	0:27	The polysialic acid mimetics idarubicin and irinotecan	0:53	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	39	theme	acid	15:18	arg1	irinotecan					44:53	irinotecan	44:53	irinotecan	44:53	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	39	theme	acid	15:18	arg1	idarubicin					29:38	idarubicin	29:38	idarubicin	29:38	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	5	40	theme	PSA-mimicking	1137:1149	arg1	analog					1193:1198	the bacterial analog	1179:1198	the bacterial analog of PSA	1179:1205	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	5	40	theme	PSA-mimicking	1137:1149	arg1	peptide					1151:1157	the PSA-mimicking peptide	1133:1157	the PSA-mimicking peptide	1133:1157	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	0	41	theme	protein	120:126	arg1	kinase					128:133	protein kinase	120:133	protein kinase	120:133	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	1	42	attach	attached	302:309	arg2	It					252:253	It	252:253	It	252:253	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	42	attach	attached	302:309	arg1	N-					314:315	N-	314:315	N-	314:315	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	42	attach	attached	302:309	arg1	glycans					333:339	O-linked glycans	324:339	O-linked glycans	324:339	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	4	43	theme	competition	1047:1057	arg1	assay					1087:1091	a competition enzyme-linked immunosorbent assay	1045:1091	a competition enzyme-linked immunosorbent assay	1045:1091	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	0	44	dep	large	165:169	arg1	charged					183:189	charged	183:189	charged	183:189	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	44	dep	large	165:169	arg1	linear					192:197	linear	192:197	linear	192:197	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	6	45	theme	protein	1390:1396	arg1	C					1405:1405	protein kinase C	1390:1405	protein kinase C	1390:1405	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	7	46	dep	compounds	1704:1712	arg1	compounds					1704:1712	the small organic compounds irinotecan and idarubicin	1686:1738	the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries	1686:1881	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	46	dep	compounds	1704:1712	arg1	idarubicin					1729:1738	idarubicin	1729:1738	idarubicin	1729:1738	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	46	dep	compounds	1704:1712	arg1	irinotecan					1714:1723	irinotecan	1714:1723	irinotecan	1714:1723	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	0	47	theme	Polysialic	138:147	arg1	homopolymer					199:209	a large, negatively charged, linear homopolymer	163:209	a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues	163:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	47	theme	Polysialic	138:147	arg1	PSA					155:157	PSA	155:157	PSA	155:157	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	47	theme	Polysialic	138:147	arg1	acid					149:152	C. Polysialic acid	135:152	C. Polysialic acid (PSA)	135:158	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	7	48	theme	PSA	1663:1665	arg1	function					1651:1658	function	1651:1658	function	1651:1658	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	48	theme	PSA	1663:1665	arg1	structure					1637:1645	structure	1637:1645	structure	1637:1645	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	6	49	theme	casein	1470:1475	arg1	kinase					1477:1482	casein kinase II	1470:1485	casein kinase II	1470:1485	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	5	50	theme	colominic	1163:1171	arg1	acid					1173:1176	colominic acid	1163:1176	colominic acid	1163:1176	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	6	51	theme	neurons	1355:1361	arg1	survival					1323:1330	survival	1323:1330	survival	1323:1330	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	6	51	theme	neurons	1355:1361	arg1	outgrowth					1309:1317	neurite outgrowth	1301:1317	neurite outgrowth	1301:1317	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	0	52	theme	C.	135:136	arg1	homopolymer					199:209	a large, negatively charged, linear homopolymer	163:209	a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues	163:249	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	52	theme	C.	135:136	arg1	PSA					155:157	PSA	155:157	PSA	155:157	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	52	theme	C.	135:136	arg1	acid					149:152	C. Polysialic acid	135:152	C. Polysialic acid (PSA)	135:158	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	7	53	dep	structure	1637:1645	arg1	the					1633:1635	the	1633:1635	the	1633:1635	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	54	theme	retargeting	1826:1836	arg1	possibility					1811:1821	the possibility	1807:1821	the possibility of retargeting	1807:1836	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	1	55	theme	neural	370:375	arg1	NCAM					401:404	NCAM	401:404	NCAM	401:404	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	55	theme	neural	370:375	arg1	molecule					391:398	the neural cell adhesion molecule	366:398	the neural cell adhesion molecule (NCAM)	366:405	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	55	theme	neural	370:375	arg1	carrier					355:361	its main carrier	346:361	its main carrier	346:361	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	6	56	dep	stimulate	1291:1299	arg1	whereas					1457:1463	whereas	1457:1463	whereas	1457:1463	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	6	57	theme	oxidative	1369:1377	arg1	stress					1379:1384	oxidative stress	1369:1384	oxidative stress	1369:1384	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	3	58	theme	immune	711:716	arg1	system					718:723	the immune system	707:723	the immune system	707:723	In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury.
28542923	1	59	theme	cell	377:380	arg1	NCAM					401:404	NCAM	401:404	NCAM	401:404	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	59	theme	cell	377:380	arg1	molecule					391:398	the neural cell adhesion molecule	366:398	the neural cell adhesion molecule (NCAM)	366:405	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	59	theme	cell	377:380	arg1	carrier					355:361	its main carrier	346:361	its main carrier	346:361	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	7	60	theme	small	1690:1694	arg1	compounds					1704:1712	the small organic compounds irinotecan and idarubicin	1686:1738	the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries	1686:1881	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	60	theme	small	1690:1694	arg1	idarubicin					1729:1738	idarubicin	1729:1738	idarubicin	1729:1738	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	60	theme	small	1690:1694	arg1	irinotecan					1714:1723	irinotecan	1714:1723	irinotecan	1714:1723	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	2	61	theme	synaptic	523:530	arg1	migration					494:502	cell migration	489:502	cell migration	489:502	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	2	61	theme	synaptic	523:530	arg1	targeting					532:540	synaptic targeting	523:540	synaptic targeting	523:540	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	1	62	theme	adhesion	382:389	arg1	NCAM					401:404	NCAM	401:404	NCAM	401:404	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	62	theme	adhesion	382:389	arg1	molecule					391:398	the neural cell adhesion molecule	366:398	the neural cell adhesion molecule (NCAM)	366:405	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	1	62	theme	adhesion	382:389	arg1	carrier					355:361	its main carrier	346:361	its main carrier	346:361	It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM).
28542923	0	63	dep	mimetics	20:27	arg1	mimetics					20:27	The polysialic acid mimetics	0:27	The polysialic acid mimetics idarubicin and irinotecan	0:53	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	63	dep	mimetics	20:27	arg1	irinotecan					44:53	irinotecan	44:53	irinotecan	44:53	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	0	63	dep	mimetics	20:27	arg1	idarubicin					29:38	idarubicin	29:38	idarubicin	29:38	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	4	64	link	enzyme-linked	1059:1071	arg1	assay					1087:1091	a competition enzyme-linked immunosorbent assay	1045:1091	a competition enzyme-linked immunosorbent assay	1045:1091	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	65	theme	small	820:824	arg1	mimetics					835:842	novel small molecule mimetics	814:842	novel small molecule mimetics of PSA that are applicable for therapy	814:881	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	66	theme	class	1016:1020	arg1	irinotecan					947:956	irinotecan	947:956	irinotecan	947:956	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	66	theme	class	1016:1020	arg1	agent					977:981	an antineoplastic agent	959:981	an antineoplastic agent of the topoisomerase I inhibitor class	959:1020	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	2	67	theme	cell-matrix	650:660	arg1	adhesions					662:670	cell-cell and cell-matrix adhesions	636:670	cell-cell and cell-matrix adhesions	636:670	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	4	68	theme	PSA	847:849	arg1	mimetics					835:842	novel small molecule mimetics	814:842	novel small molecule mimetics of PSA that are applicable for therapy	814:881	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	6	69	theme	neurite	1584:1590	arg1	outgrowth					1592:1600	irinotecan-stimulated neurite outgrowth	1562:1600	irinotecan-stimulated neurite outgrowth	1562:1600	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	4	70	theme	PSA	1026:1028	arg1	irinotecan					947:956	irinotecan	947:956	irinotecan	947:956	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	70	theme	PSA	1026:1028	arg1	mimetics					1030:1037	PSA mimetics	1026:1037	PSA mimetics using a competition enzyme-linked immunosorbent assay	1026:1091	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	70	theme	PSA	1026:1028	arg1	idarubicin					898:907	idarubicin	898:907	idarubicin	898:907	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	3	71	theme	functional	751:760	arg1	recovery					762:769	functional recovery	751:769	functional recovery after nervous system injury	751:797	In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury.
28542923	2	72	theme	nervous	461:467	arg1	system					469:474	the nervous system	457:474	the nervous system	457:474	PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions.
28542923	7	73	theme	same	1758:1761	arg1	cascades					1773:1780	the same signaling cascades	1754:1780	the same signaling cascades as PSA	1754:1787	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	5	74	theme	PSA	1203:1205	arg1	analog					1193:1198	the bacterial analog	1179:1198	the bacterial analog of PSA	1179:1205	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	5	74	theme	PSA	1203:1205	arg1	peptide					1151:1157	the PSA-mimicking peptide	1133:1157	the PSA-mimicking peptide	1133:1157	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	6	75	theme	colominic	1441:1449	arg1	acid					1451:1454	colominic acid	1441:1454	colominic acid	1441:1454	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	5	76	theme	monoclonal	1240:1249	arg1	antibody					1251:1258	the PSA-specific monoclonal antibody 735	1223:1262	the PSA-specific monoclonal antibody 735	1223:1262	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	3	77	theme	PSA	730:732	arg1	mimetics					734:741	PSA mimetics	730:741	PSA mimetics	730:741	In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury.
28542923	0	78	theme	neuronal	65:72	arg1	survival					74:81	neuronal survival	65:81	neuronal survival	65:81	The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C. Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues.
28542923	6	79	theme	kinase	1398:1403	arg1	C					1405:1405	protein kinase C	1390:1405	protein kinase C	1390:1405	Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth.
28542923	5	80	theme	PSA-specific	1227:1238	arg1	antibody					1251:1258	the PSA-specific monoclonal antibody 735	1223:1262	the PSA-specific monoclonal antibody 735	1223:1262	Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735.
28542923	4	81	theme	antineoplastic	962:975	arg1	irinotecan					947:956	irinotecan	947:956	irinotecan	947:956	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	81	theme	antineoplastic	962:975	arg1	agent					977:981	an antineoplastic agent	959:981	an antineoplastic agent of the topoisomerase I inhibitor class	959:1020	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	4	82	theme	topoisomerase	990:1002	arg1	class					1016:1020	the topoisomerase I inhibitor class	986:1020	the topoisomerase I inhibitor class	986:1020	In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay.
28542923	7	83	theme	organic	1696:1702	arg1	compounds					1704:1712	the small organic compounds irinotecan and idarubicin	1686:1738	the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries	1686:1881	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	83	theme	organic	1696:1702	arg1	idarubicin					1729:1738	idarubicin	1729:1738	idarubicin	1729:1738	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28542923	7	83	theme	organic	1696:1702	arg1	irinotecan					1714:1723	irinotecan	1714:1723	irinotecan	1714:1723	These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.
28469279	6	0	theme	mouse	921:925	arg1	model					927:931	an experimental mouse model	905:931	an experimental mouse model of chronic kidney disease	905:957	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	6	1	from	role	1011:1014	arg1	cells					1053:1057	dividing epithelial cells	1033:1057	dividing epithelial cells	1033:1057	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	6	2	theme	experimental	908:919	arg1	model					927:931	an experimental mouse model	905:931	an experimental mouse model of chronic kidney disease	905:957	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	4	3	theme	interphase	708:717	arg1	cells					742:746	interphase and mitotic epithelial cells	708:746	interphase and mitotic epithelial cells	708:746	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	4	from	component	695:703	arg1	cells					742:746	interphase and mitotic epithelial cells	708:746	interphase and mitotic epithelial cells	708:746	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	5	theme	excellent	611:619	arg1	Galectin-3					546:555	Galectin-3	546:555	Galectin-3	546:555	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	5	theme	excellent	611:619	arg1	candidate					621:629	an excellent candidate	608:629	an excellent candidate	608:629	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	8	6	theme	novel	1375:1379	arg1	Galectin-3					1359:1368	Galectin-3	1359:1368	Galectin-3	1359:1368	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	8	6	theme	novel	1375:1379	arg1	contributor					1381:1391	a novel contributor	1373:1391	a novel contributor to epithelial mitotic progress	1373:1422	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	3	7	theme	correct	523:529	arg1	division					536:543	correct cell division	523:543	correct cell division	523:543	As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division.
28469279	8	8	theme	NuMA	1300:1303	arg1	localization					1305:1316	stable NuMA localization	1293:1316	stable NuMA localization to the spindle pole	1293:1336	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	8	9	theme	spindle	1268:1274	arg1	cohesion					1276:1283	mitotic spindle cohesion	1260:1283	mitotic spindle cohesion	1260:1283	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	2	10	theme	glycosylation	156:168	arg1	pathway					170:176	One glycosylation pathway	152:176	One glycosylation pathway	152:176	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	10	theme	glycosylation	156:168	arg1	glycosylation					222:234	the unusual O-linked β-N-acetylglucosamine glycosylation	179:234	the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	179:252	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	3	11	theme	mitotic	464:470	arg1	proteins					487:494	mitotic O-GlcNAcylated proteins	464:494	mitotic O-GlcNAcylated proteins during metaphase	464:511	As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division.
28469279	0	12	theme	pole	8:11	arg1	cohesion					13:20	Spindle pole cohesion	0:20	Spindle pole cohesion	0:20	Spindle pole cohesion requires glycosylation-mediated localization of NuMA.
28469279	4	13	theme	Galectin	588:595	arg1	family					597:602	the Galectin family	584:602	the Galectin family	584:602	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	3	14	gly	glycosylated	398:409	arg1	proteins					411:418	glycosylated proteins	398:418	glycosylated proteins	398:418	As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division.
28469279	2	15	theme	proteins	331:338	arg1	subset					321:326	a subset	319:326	a subset of proteins that are O-GlcNAcylated during metaphase	319:379	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	4	16	theme	centrosomal	683:693	arg1	component					695:703	a transient centrosomal component	671:703	a transient centrosomal component in interphase and mitotic epithelial cells	671:746	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	16	theme	centrosomal	683:693	arg1	it					635:636	it	635:636	it	635:636	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	0	17	theme	Spindle	0:6	arg1	cohesion					13:20	Spindle pole cohesion	0:20	Spindle pole cohesion	0:20	Spindle pole cohesion requires glycosylation-mediated localization of NuMA.
28469279	6	18	theme	cell	980:983	arg1	lines					985:989	human epithelial cell lines	963:989	human epithelial cell lines	963:989	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	2	19	link	O-linked	191:198	arg1	pathway					170:176	One glycosylation pathway	152:176	One glycosylation pathway	152:176	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	19	link	O-linked	191:198	arg1	O-GlcNAcylation					237:251	O-GlcNAcylation	237:251	O-GlcNAcylation	237:251	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	19	link	O-linked	191:198	arg1	glycosylation					222:234	the unusual O-linked β-N-acetylglucosamine glycosylation	179:234	the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	179:252	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	5	20	theme	motile	823:828	arg1	cilia					830:834	motile cilia	823:834	motile cilia	823:834	In addition, it has recently been shown to associate with basal bodies in motile cilia, where it stabilizes the microtubule-organizing center (MTOC).
28469279	6	21	theme	epithelial	969:978	arg1	lines					985:989	human epithelial cell lines	963:989	human epithelial cell lines	963:989	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	6	22	theme	human	963:967	arg1	lines					985:989	human epithelial cell lines	963:989	human epithelial cell lines	963:989	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	6	23	theme	dividing	1033:1040	arg1	cells					1053:1057	dividing epithelial cells	1033:1057	dividing epithelial cells	1033:1057	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	3	24	theme	glycosylated	398:409	arg1	proteins					411:418	glycosylated proteins	398:418	glycosylated proteins	398:418	As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division.
28469279	4	25	theme	family	597:602	arg1	lectin					574:579	a small soluble lectin	558:579	a small soluble lectin of the Galectin family	558:602	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	25	theme	family	597:602	arg1	Galectin-3					546:555	Galectin-3	546:555	Galectin-3	546:555	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	2	26	theme	β-N-acetylglucosamine	200:220	arg1	pathway					170:176	One glycosylation pathway	152:176	One glycosylation pathway	152:176	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	26	theme	β-N-acetylglucosamine	200:220	arg1	O-GlcNAcylation					237:251	O-GlcNAcylation	237:251	O-GlcNAcylation	237:251	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	26	theme	β-N-acetylglucosamine	200:220	arg1	glycosylation					222:234	the unusual O-linked β-N-acetylglucosamine glycosylation	179:234	the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	179:252	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	6	27	theme	epithelial	1042:1051	arg1	cells					1053:1057	dividing epithelial cells	1033:1057	dividing epithelial cells	1033:1057	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	8	28	theme	NuMA-Galectin-3	1215:1229	arg1	important					1246:1254	important	1246:1254	important	1246:1254	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	8	28	theme	NuMA-Galectin-3	1215:1229	arg1	interaction					1231:1241	the NuMA-Galectin-3 interaction	1211:1241	the NuMA-Galectin-3 interaction	1211:1241	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	3	29	theme	cell	531:534	arg1	division					536:543	correct cell division	523:543	correct cell division	523:543	As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division.
28469279	2	30	theme	O-linked	191:198	arg1	pathway					170:176	One glycosylation pathway	152:176	One glycosylation pathway	152:176	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	30	theme	O-linked	191:198	arg1	O-GlcNAcylation					237:251	O-GlcNAcylation	237:251	O-GlcNAcylation	237:251	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	30	theme	O-linked	191:198	arg1	glycosylation					222:234	the unusual O-linked β-N-acetylglucosamine glycosylation	179:234	the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	179:252	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	8	31	theme	mitotic	1407:1413	arg1	progress					1415:1422	epithelial mitotic progress	1396:1422	epithelial mitotic progress	1396:1422	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	4	32	theme	transient	673:681	arg1	component					695:703	a transient centrosomal component	671:703	a transient centrosomal component in interphase and mitotic epithelial cells	671:746	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	32	theme	transient	673:681	arg1	it					635:636	it	635:636	it	635:636	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	3	33	theme	O-GlcNAcylated	472:485	arg1	proteins					487:494	mitotic O-GlcNAcylated proteins	464:494	mitotic O-GlcNAcylated proteins during metaphase	464:511	As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division.
28469279	0	34	theme	glycosylation-mediated	31:52	arg1	localization					54:65	glycosylation-mediated localization	31:65	glycosylation-mediated localization of NuMA	31:73	Spindle pole cohesion requires glycosylation-mediated localization of NuMA.
28469279	4	35	theme	small	560:564	arg1	lectin					574:579	a small soluble lectin	558:579	a small soluble lectin of the Galectin family	558:602	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	35	theme	small	560:564	arg1	Galectin-3					546:555	Galectin-3	546:555	Galectin-3	546:555	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	3	36	theme	specific	433:440	arg1	lectins					442:448	specific lectins	433:448	specific lectins	433:448	As lectins bind glycosylated proteins, we asked if specific lectins interact with mitotic O-GlcNAcylated proteins during metaphase to ensure correct cell division.
28469279	2	37	theme	unusual	183:189	arg1	pathway					170:176	One glycosylation pathway	152:176	One glycosylation pathway	152:176	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	37	theme	unusual	183:189	arg1	O-GlcNAcylation					237:251	O-GlcNAcylation	237:251	O-GlcNAcylation	237:251	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	2	37	theme	unusual	183:189	arg1	glycosylation					222:234	the unusual O-linked β-N-acetylglucosamine glycosylation	179:234	the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	179:252	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	8	38	theme	epithelial	1396:1405	arg1	progress					1415:1422	epithelial mitotic progress	1396:1422	epithelial mitotic progress	1396:1422	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	0	39	theme	NuMA	70:73	arg1	localization					54:65	glycosylation-mediated localization	31:65	glycosylation-mediated localization of NuMA	31:73	Spindle pole cohesion requires glycosylation-mediated localization of NuMA.
28469279	6	40	theme	kidney	944:949	arg1	disease					951:957	chronic kidney disease	936:957	chronic kidney disease	936:957	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	8	41	theme	mitotic	1260:1266	arg1	cohesion					1276:1283	mitotic spindle cohesion	1260:1283	mitotic spindle cohesion	1260:1283	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	5	42	from	bodies	813:818	arg1	cilia					830:834	motile cilia	823:834	motile cilia	823:834	In addition, it has recently been shown to associate with basal bodies in motile cilia, where it stabilizes the microtubule-organizing center (MTOC).
28469279	1	43	theme	several	124:130	arg1	processes					141:149	several cellular processes	124:149	several cellular processes	124:149	Glycosylation is critical for the regulation of several cellular processes.
28469279	5	44	theme	basal	807:811	arg1	bodies					813:818	basal bodies	807:818	basal bodies in motile cilia, where it stabilizes the microtubule-organizing center (MTOC)	807:896	In addition, it has recently been shown to associate with basal bodies in motile cilia, where it stabilizes the microtubule-organizing center (MTOC).
28469279	6	45	theme	chronic	936:942	arg1	disease					951:957	chronic kidney disease	936:957	chronic kidney disease	936:957	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	1	46	theme	cellular	132:139	arg1	processes					141:149	several cellular processes	124:149	several cellular processes	124:149	Glycosylation is critical for the regulation of several cellular processes.
28469279	6	47	theme	disease	951:957	arg1	lines					985:989	human epithelial cell lines	963:989	human epithelial cell lines	963:989	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	6	47	theme	disease	951:957	arg1	model					927:931	an experimental mouse model	905:931	an experimental mouse model of chronic kidney disease	905:957	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	4	48	theme	soluble	566:572	arg1	lectin					574:579	a small soluble lectin	558:579	a small soluble lectin of the Galectin family	558:602	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	48	theme	soluble	566:572	arg1	Galectin-3					546:555	Galectin-3	546:555	Galectin-3	546:555	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	4	49	theme	epithelial	731:740	arg1	cells					742:746	interphase and mitotic epithelial cells	708:746	interphase and mitotic epithelial cells	708:746	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28469279	2	50	theme	proper	288:293	arg1	mitosis					295:301	proper mitosis	288:301	proper mitosis	288:301	One glycosylation pathway, the unusual O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) has been shown to be required for proper mitosis, likely through a subset of proteins that are O-GlcNAcylated during metaphase.
28469279	1	51	theme	processes	141:149	arg1	regulation					110:119	the regulation	106:119	the regulation of several cellular processes	106:149	Glycosylation is critical for the regulation of several cellular processes.
28469279	6	52	theme	Galectin-3	1019:1028	arg1	role					1011:1014	the role	1007:1014	the role of Galectin-3 in dividing epithelial cells	1007:1057	Using an experimental mouse model of chronic kidney disease and human epithelial cell lines, we investigate the role of Galectin-3 in dividing epithelial cells.
28469279	8	53	theme	stable	1293:1298	arg1	localization					1305:1316	stable NuMA localization	1293:1316	stable NuMA localization to the spindle pole	1293:1336	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	5	54	theme	microtubule-organizing	861:882	arg1	MTOC					892:895	MTOC	892:895	MTOC	892:895	In addition, it has recently been shown to associate with basal bodies in motile cilia, where it stabilizes the microtubule-organizing center (MTOC).
28469279	5	54	theme	microtubule-organizing	861:882	arg1	center					884:889	the microtubule-organizing center	857:889	the microtubule-organizing center (MTOC)	857:896	In addition, it has recently been shown to associate with basal bodies in motile cilia, where it stabilizes the microtubule-organizing center (MTOC).
28469279	7	55	theme	O-GlcNAcylation-dependent	1152:1176	arg1	manner					1178:1183	an O-GlcNAcylation-dependent manner	1149:1183	an O-GlcNAcylation-dependent manner	1149:1183	Here we find that Galectin-3 is essential for metaphase where it associates with NuMA in an O-GlcNAcylation-dependent manner.
28469279	8	56	theme	spindle	1325:1331	arg1	pole					1333:1336	the spindle pole	1321:1336	the spindle pole	1321:1336	We provide evidence that the NuMA-Galectin-3 interaction is important for mitotic spindle cohesion and for stable NuMA localization to the spindle pole, thus revealing that Galectin-3 is a novel contributor to epithelial mitotic progress.
28469279	4	57	theme	mitotic	723:729	arg1	cells					742:746	interphase and mitotic epithelial cells	708:746	interphase and mitotic epithelial cells	708:746	Galectin-3, a small soluble lectin of the Galectin family, is an excellent candidate, as it has been previously described as a transient centrosomal component in interphase and mitotic epithelial cells.
28411811	6	0	theme	detection	1202:1210	arg1	sensitivity					1212:1222	a low nanogram detection sensitivity	1187:1222	a low nanogram detection sensitivity	1187:1222	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	10	1	theme	O-GlcNAc	1851:1858	arg1	peptides					1860:1867	O-GlcNAc peptides	1851:1867	O-GlcNAc peptides	1851:1867	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	10	2	from	enrichment	1818:1827	arg1	efficient					1794:1802	efficient	1794:1802	efficient	1794:1802	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	2	3	theme	nutrient	298:305	arg1	It					277:278	It	277:278	It	277:278	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	3	theme	nutrient	298:305	arg1	sensor					307:312	a major nutrient sensor	290:312	a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation	290:453	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	9	4	theme	related	1622:1628	arg1	proteins					1613:1620	unreported O-GlcNAc proteins	1593:1620	unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process	1593:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	10	5	from	identification	1833:1846	arg1	efficient					1794:1802	efficient	1794:1802	efficient	1794:1802	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	5	6	theme	enzymatic	946:954	arg1	deglycosylation					956:970	selective enzymatic deglycosylation	936:970	selective enzymatic deglycosylation	936:970	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	8	7	theme	O-GlcNAc	1380:1387	arg1	peptides					1389:1396	474 O-GlcNAc peptides	1376:1396	474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins	1376:1435	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	1	8	gly	glycosylation	214:226	arg1	proteins					267:274	nucleocytoplasmic and mitochondrial proteins	231:274	nucleocytoplasmic and mitochondrial proteins	231:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	2	9	theme	numerous	326:333	arg1	degradation					443:453	protein degradation	435:453	protein degradation	435:453	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	9	theme	numerous	326:333	arg1	processes					346:354	numerous biological processes	326:354	numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation	326:453	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	9	theme	numerous	326:333	arg1	regulation					382:391	transcriptional regulation	366:391	transcriptional regulation	366:391	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	9	theme	numerous	326:333	arg1	metabolism					399:408	cell metabolism	394:408	cell metabolism	394:408	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	9	theme	numerous	326:333	arg1	signaling					420:428	cellular signaling	411:428	cellular signaling	411:428	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	10	10	dep	enrichment	1818:1827	arg1	the					1807:1809	the	1807:1809	the	1807:1809	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	0	11	theme	HILIC	113:117	arg1	enrichment					119:128	HILIC enrichment	113:128	HILIC enrichment	113:128	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	1	12	theme	O-linked	205:212	arg1	glycosylation					214:226	dynamic O-linked glycosylation	197:226	dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins	197:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	3	13	theme	cellular	473:480	arg1	levels					497:502	cellular O-GlcNAcylated levels	473:502	cellular O-GlcNAcylated levels	473:502	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	4	14	theme	low	709:711	arg1	stoichiometry					713:725	its extremely low stoichiometry	695:725	its extremely low stoichiometry	695:725	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	9	15	theme	proteins	1613:1620	arg1	number					1583:1588	A large number	1575:1588	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process	1575:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	4	16	theme	large-scale	779:789	arg1	identification					791:804	large-scale identification	779:804	large-scale identification by mass spectrometry	779:825	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	0	17	theme	spectrometry	139:150	arg1	identification					152:165	mass spectrometry identification	134:165	mass spectrometry identification	134:165	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	6	18	theme	O-GlcNAc	1031:1038	arg1	peptides					1040:1047	Standard O-GlcNAc peptides	1022:1047	Standard O-GlcNAc peptides	1022:1047	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	11	19	theme	new	1889:1891	arg1	insights					1893:1900	new insights	1889:1900	new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body	1889:2053	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	11	20	theme	human	2138:2142	arg1	urine					2144:2148	human urine	2138:2148	human urine	2138:2148	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	6	21	theme	non-O-GlcNAc	1124:1135	arg1	peptides					1137:1144	500-fold more abundant non-O-GlcNAc peptides	1101:1144	500-fold more abundant non-O-GlcNAc peptides	1101:1144	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	8	22	theme	mass	1456:1459	arg1	analysis					1474:1481	mass spectrometry analysis	1456:1481	mass spectrometry analysis	1456:1481	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	0	23	theme	proteins	48:55	arg1	mapping					28:34	global mapping	21:34	global mapping of O-GlcNAc proteins and peptides	21:68	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	9	24	theme	biological	1645:1654	arg1	cycle					1638:1642	cell cycle	1633:1642	cell cycle	1633:1642	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	9	24	theme	biological	1645:1654	arg1	regulation					1656:1665	biological regulation	1645:1665	biological regulation	1645:1665	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	4	25	theme	approaches	764:773	arg1	stoichiometry					713:725	its extremely low stoichiometry	695:725	its extremely low stoichiometry	695:725	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	4	25	theme	approaches	764:773	arg1	lack					735:738	the lack	731:738	the lack of efficient enrichment approaches for large-scale identification by mass spectrometry	731:825	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	11	26	theme	biological	1911:1920	arg1	function					1922:1929	the biological function	1907:1929	the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body	1907:2053	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	0	27	theme	peptides	61:68	arg1	mapping					28:34	global mapping	21:34	global mapping of O-GlcNAc proteins and peptides	21:68	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	5	28	theme	mass	994:997	arg1	analysis					1012:1019	mass spectrometry analysis	994:1019	mass spectrometry analysis	994:1019	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	9	29	located	found	1709:1713	arg1	data					1722:1725	our data	1718:1725	our data	1718:1725	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	9	29	located	found	1709:1713	arg2	number					1583:1588	A large number	1575:1588	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process	1575:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	7	30	from	enrichment	1283:1292	arg1	urine					1358:1362	human urine	1352:1362	human urine	1352:1362	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	0	31	theme	selective	76:84	arg1	deglycosylation					96:110	selective enzymatic deglycosylation	76:110	selective enzymatic deglycosylation	76:110	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	7	32	from	characterization	1298:1313	arg1	urine					1358:1362	human urine	1352:1362	human urine	1352:1362	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	3	33	theme	O-GlcNAcylated	482:495	arg1	levels					497:502	cellular O-GlcNAcylated levels	473:502	cellular O-GlcNAcylated levels	473:502	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	5	34	theme	novel	851:855	arg1	strategy					857:864	a novel strategy	849:864	a novel strategy for the global identification of O-GlcNAc proteins and peptides	849:928	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	10	35	theme	novel	1769:1773	arg1	strategy					1775:1782	this novel strategy	1764:1782	this novel strategy	1764:1782	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	3	36	theme	neurodegenerative	569:585	arg1	disease					587:593	neurodegenerative disease	569:593	neurodegenerative disease	569:593	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	11	37	theme	human	2044:2048	arg1	body					2050:2053	human body	2044:2053	human body	2044:2053	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	7	38	theme	O-GlcNAc	1318:1325	arg1	proteins					1327:1334	O-GlcNAc proteins	1318:1334	O-GlcNAc proteins	1318:1334	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	6	39	with	spectrometry	1169:1180	arg1	sensitivity					1212:1222	a low nanogram detection sensitivity	1187:1222	a low nanogram detection sensitivity	1187:1222	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	8	40	theme	more	1514:1517	arg1	times					1508:1512	at least three times	1493:1512	at least three times more than that obtained by commonly used enrichment methods	1493:1572	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	10	41	theme	global	1811:1816	arg1	enrichment					1818:1827	global enrichment	1811:1827	global enrichment	1811:1827	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	5	42	theme	O-GlcNAc	899:906	arg1	proteins					908:915	O-GlcNAc proteins	899:915	O-GlcNAc proteins	899:915	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	4	43	theme	efficient	743:751	arg1	approaches					764:773	efficient enrichment approaches	743:773	efficient enrichment approaches for large-scale identification by mass spectrometry	743:825	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	4	44	theme	deeper	616:621	arg1	insight					623:629	deeper insight	616:629	deeper insight into the biological mechanism of O-GlcNAcylation	616:678	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	0	45	theme	global	21:26	arg1	mapping					28:34	global mapping	21:34	global mapping of O-GlcNAc proteins and peptides	21:68	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	3	46	theme	diseases	542:549	arg1	etiologies					523:532	the etiologies	519:532	the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer	519:604	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	7	47	theme	first	1265:1269	arg1	enrichment					1283:1292	first large-scale enrichment	1265:1292	first large-scale enrichment	1265:1292	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	8	48	theme	used	1550:1553	arg1	methods					1566:1572	commonly used enrichment methods	1541:1572	commonly used enrichment methods	1541:1572	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	1	49	theme	nucleocytoplasmic	231:247	arg1	proteins					267:274	nucleocytoplasmic and mitochondrial proteins	231:274	nucleocytoplasmic and mitochondrial proteins	231:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	11	50	theme	pathological	2020:2031	arg1	changes					2033:2039	pathological changes	2020:2039	pathological changes	2020:2039	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	1	51	theme	mitochondrial	253:265	arg1	proteins					267:274	nucleocytoplasmic and mitochondrial proteins	231:274	nucleocytoplasmic and mitochondrial proteins	231:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	6	52	theme	Standard	1022:1029	arg1	peptides					1040:1047	Standard O-GlcNAc peptides	1022:1047	Standard O-GlcNAc peptides	1022:1047	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	11	53	from	urine	2144:2148	arg1	discovery					2123:2131	biomarker discovery	2113:2131	biomarker discovery from human urine	2113:2148	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	2	54	theme	cell	394:397	arg1	metabolism					399:408	cell metabolism	394:408	cell metabolism	394:408	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	6	55	theme	nanogram	1193:1200	arg1	sensitivity					1212:1222	a low nanogram detection sensitivity	1187:1222	a low nanogram detection sensitivity	1187:1222	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	4	56	theme	biological	640:649	arg1	mechanism					651:659	the biological mechanism	636:659	the biological mechanism of O-GlcNAcylation	636:678	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	2	57	theme	major	292:296	arg1	It					277:278	It	277:278	It	277:278	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	57	theme	major	292:296	arg1	sensor					307:312	a major nutrient sensor	290:312	a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation	290:453	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	5	58	theme	selective	936:944	arg1	deglycosylation					956:970	selective enzymatic deglycosylation	936:970	selective enzymatic deglycosylation	936:970	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	10	59	theme	above	1732:1736	arg1	results					1738:1744	The above results	1728:1744	The above results	1728:1744	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	2	60	theme	biological	335:344	arg1	degradation					443:453	protein degradation	435:453	protein degradation	435:453	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	60	theme	biological	335:344	arg1	processes					346:354	numerous biological processes	326:354	numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation	326:453	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	60	theme	biological	335:344	arg1	regulation					382:391	transcriptional regulation	366:391	transcriptional regulation	366:391	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	60	theme	biological	335:344	arg1	metabolism					399:408	cell metabolism	394:408	cell metabolism	394:408	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	2	60	theme	biological	335:344	arg1	signaling					420:428	cellular signaling	411:428	cellular signaling	411:428	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	9	61	theme	large	1577:1581	arg1	number					1583:1588	A large number	1575:1588	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process	1575:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	11	62	theme	human	1953:1957	arg1	urine					1959:1963	human urine	1953:1963	human urine	1953:1963	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	1	63	theme	dynamic	197:203	arg1	glycosylation					214:226	dynamic O-linked glycosylation	197:226	dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins	197:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	8	64	theme	spectrometry	1461:1472	arg1	analysis					1474:1481	mass spectrometry analysis	1456:1481	mass spectrometry analysis	1456:1481	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	8	65	theme	peptides	1389:1396	arg1	total					1367:1371	A total	1365:1371	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins	1365:1435	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	11	66	theme	O-GlcNAcylation	1934:1948	arg1	function					1922:1929	the biological function	1907:1929	the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body	1907:2053	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	0	67	theme	mass	134:137	arg1	identification					152:165	mass spectrometry identification	134:165	mass spectrometry identification	134:165	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	11	68	theme	strategy	2100:2107	arg1	potential					2082:2090	the potential	2078:2090	the potential of this strategy for biomarker discovery from human urine	2078:2148	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	5	69	theme	peptides	921:928	arg1	identification					881:894	the global identification	870:894	the global identification of O-GlcNAc proteins and peptides	870:928	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	11	70	from	function	1922:1929	arg1	urine					1959:1963	human urine	1953:1963	human urine	1953:1963	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	8	71	theme	457	1415:1417	arg1	proteins					1428:1435	457 O-GlcNAc proteins	1415:1435	457 O-GlcNAc proteins	1415:1435	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	7	72	theme	peptides	1340:1347	arg1	characterization					1298:1313	characterization	1298:1313	characterization	1298:1313	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	7	72	theme	peptides	1340:1347	arg1	enrichment					1283:1292	first large-scale enrichment	1265:1292	first large-scale enrichment	1265:1292	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	5	73	theme	spectrometry	999:1010	arg1	analysis					1012:1019	mass spectrometry analysis	994:1019	mass spectrometry analysis	994:1019	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	8	74	theme	O-GlcNAc	1419:1426	arg1	proteins					1428:1435	457 O-GlcNAc proteins	1415:1435	457 O-GlcNAc proteins	1415:1435	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	9	75	theme	cell	1633:1636	arg1	process					1696:1702	metabolic and developmental process	1668:1702	metabolic and developmental process	1668:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	9	75	theme	cell	1633:1636	arg1	cycle					1638:1642	cell cycle	1633:1642	cell cycle	1633:1642	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	9	75	theme	cell	1633:1636	arg1	regulation					1656:1665	biological regulation	1645:1665	biological regulation	1645:1665	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	6	76	theme	peptides	1137:1144	arg1	presence					1089:1096	the presence	1085:1096	the presence of 500-fold more abundant non-O-GlcNAc peptides	1085:1144	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	11	77	theme	biomarker	2113:2121	arg1	discovery					2123:2131	biomarker discovery	2113:2131	biomarker discovery from human urine	2113:2148	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	5	78	theme	proteins	908:915	arg1	identification					881:894	the global identification	870:894	the global identification of O-GlcNAc proteins and peptides	870:928	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	5	79	theme	HILIC	973:977	arg1	enrichment					979:988	HILIC enrichment	973:988	HILIC enrichment	973:988	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	6	80	theme	abundant	1115:1122	arg1	peptides					1137:1144	500-fold more abundant non-O-GlcNAc peptides	1101:1144	500-fold more abundant non-O-GlcNAc peptides	1101:1144	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	7	81	theme	human	1352:1356	arg1	urine					1358:1362	human urine	1352:1362	human urine	1352:1362	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	6	82	theme	500-fold	1101:1108	arg1	peptides					1137:1144	500-fold more abundant non-O-GlcNAc peptides	1101:1144	500-fold more abundant non-O-GlcNAc peptides	1101:1144	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	4	83	theme	enrichment	753:762	arg1	approaches					764:773	efficient enrichment approaches	743:773	efficient enrichment approaches for large-scale identification by mass spectrometry	743:825	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	0	84	theme	enzymatic	86:94	arg1	deglycosylation					96:110	selective enzymatic deglycosylation	76:110	selective enzymatic deglycosylation	76:110	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	9	85	theme	metabolic	1668:1676	arg1	cycle					1638:1642	cell cycle	1633:1642	cell cycle	1633:1642	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	9	85	theme	metabolic	1668:1676	arg1	process					1696:1702	metabolic and developmental process	1668:1702	metabolic and developmental process	1668:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	1	86	link	O-linked	205:212	arg1	glycosylation					214:226	dynamic O-linked glycosylation	197:226	dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins	197:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	7	87	theme	proteins	1327:1334	arg1	characterization					1298:1313	characterization	1298:1313	characterization	1298:1313	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	7	87	theme	proteins	1327:1334	arg1	enrichment					1283:1292	first large-scale enrichment	1265:1292	first large-scale enrichment	1265:1292	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	9	88	theme	unreported	1593:1602	arg1	proteins					1613:1620	unreported O-GlcNAc proteins	1593:1620	unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process	1593:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	9	89	theme	developmental	1682:1694	arg1	cycle					1638:1642	cell cycle	1633:1642	cell cycle	1633:1642	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	9	89	theme	developmental	1682:1694	arg1	process					1696:1702	metabolic and developmental process	1668:1702	metabolic and developmental process	1668:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	6	90	theme	low	1189:1191	arg1	sensitivity					1212:1222	a low nanogram detection sensitivity	1187:1222	a low nanogram detection sensitivity	1187:1222	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	1	91	theme	glycosylation	214:226	arg1	kind					189:192	a kind	187:192	a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins	187:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	1	91	theme	glycosylation	214:226	arg1	O-GlcNAcylation					168:182	O-GlcNAcylation	168:182	O-GlcNAcylation	168:182	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28411811	3	92	theme	levels	497:502	arg1	Dysregulation					456:468	Dysregulation	456:468	Dysregulation of cellular O-GlcNAcylated levels	456:502	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	5	93	theme	global	874:879	arg1	identification					881:894	the global identification	870:894	the global identification of O-GlcNAc proteins and peptides	870:928	Herein, we developed a novel strategy for the global identification of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry analysis.
28411811	7	94	dep	enrichment	1283:1292	arg1	the					1261:1263	the	1261:1263	the	1261:1263	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	4	95	theme	mass	809:812	arg1	spectrometry					814:825	mass spectrometry	809:825	mass spectrometry	809:825	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	2	96	theme	cellular	411:418	arg1	signaling					420:428	cellular signaling	411:428	cellular signaling	411:428	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	6	97	theme	mass	1164:1167	arg1	spectrometry					1169:1180	mass spectrometry	1164:1180	mass spectrometry with a low nanogram detection sensitivity	1164:1222	Standard O-GlcNAc peptides can be efficiently enriched even in the presence of 500-fold more abundant non-O-GlcNAc peptides and identified by mass spectrometry with a low nanogram detection sensitivity.
28411811	7	98	theme	large-scale	1271:1281	arg1	enrichment					1283:1292	first large-scale enrichment	1265:1292	first large-scale enrichment	1265:1292	This strategy successfully achieved the first large-scale enrichment and characterization of O-GlcNAc proteins and peptides in human urine.
28411811	9	99	theme	O-GlcNAc	1604:1611	arg1	proteins					1613:1620	unreported O-GlcNAc proteins	1593:1620	unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process	1593:1702	A large number of unreported O-GlcNAc proteins related to cell cycle, biological regulation, metabolic and developmental process were found in our data.
28411811	11	100	theme	body	2050:2053	arg1	states					2009:2014	the physiological states	1991:2014	the physiological states	1991:2014	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	11	100	theme	body	2050:2053	arg1	changes					2033:2039	pathological changes	2020:2039	pathological changes	2020:2039	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	2	101	theme	protein	435:441	arg1	degradation					443:453	protein degradation	435:453	protein degradation	435:453	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	0	102	theme	O-GlcNAc	39:46	arg1	proteins					48:55	O-GlcNAc proteins	39:55	O-GlcNAc proteins	39:55	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	2	103	theme	transcriptional	366:380	arg1	regulation					382:391	transcriptional regulation	366:391	transcriptional regulation	366:391	It serves as a major nutrient sensor to regulate numerous biological processes including transcriptional regulation, cell metabolism, cellular signaling, and protein degradation.
28411811	11	104	theme	physiological	1995:2007	arg1	states					2009:2014	the physiological states	1991:2014	the physiological states	1991:2014	These data provide new insights into the biological function of O-GlcNAcylation in human urine, which is correlated with the physiological states and pathological changes of human body and therefore indicate the potential of this strategy for biomarker discovery from human urine.
28411811	4	105	theme	O-GlcNAcylation	664:678	arg1	mechanism					651:659	the biological mechanism	636:659	the biological mechanism of O-GlcNAcylation	636:678	However, deeper insight into the biological mechanism of O-GlcNAcylation is hampered by its extremely low stoichiometry and the lack of efficient enrichment approaches for large-scale identification by mass spectrometry.
28411811	3	106	theme	many	537:540	arg1	diseases					542:549	many diseases	537:549	many diseases such as diabetes, neurodegenerative disease and cancer	537:604	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	3	106	theme	many	537:540	arg1	cancer					599:604	cancer	599:604	cancer	599:604	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	3	106	theme	many	537:540	arg1	disease					587:593	neurodegenerative disease	569:593	neurodegenerative disease	569:593	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	3	106	theme	many	537:540	arg1	diabetes					559:566	diabetes	559:566	diabetes	559:566	Dysregulation of cellular O-GlcNAcylated levels contributes to the etiologies of many diseases such as diabetes, neurodegenerative disease and cancer.
28411811	10	107	from	efficient	1794:1802	arg1	identification					1833:1846	identification	1833:1846	identification	1833:1846	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	10	107	from	efficient	1794:1802	arg1	enrichment					1818:1827	global enrichment	1811:1827	global enrichment	1811:1827	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	10	108	theme	peptides	1860:1867	arg1	identification					1833:1846	identification	1833:1846	identification	1833:1846	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	10	108	theme	peptides	1860:1867	arg1	enrichment					1818:1827	global enrichment	1811:1827	global enrichment	1811:1827	The above results demonstrated that this novel strategy is highly efficient in the global enrichment and identification of O-GlcNAc peptides.
28411811	8	109	theme	enrichment	1555:1564	arg1	methods					1566:1572	commonly used enrichment methods	1541:1572	commonly used enrichment methods	1541:1572	A total of 474 O-GlcNAc peptides corresponding to 457 O-GlcNAc proteins were identified by mass spectrometry analysis, which is at least three times more than that obtained by commonly used enrichment methods.
28411811	0	110	theme	novel	2:6	arg1	strategy					8:15	A novel strategy	0:15	A novel strategy for global mapping of O-GlcNAc proteins and peptides	0:68	A novel strategy for global mapping of O-GlcNAc proteins and peptides using selective enzymatic deglycosylation, HILIC enrichment and mass spectrometry identification.
28411811	1	111	theme	proteins	267:274	arg1	glycosylation					214:226	dynamic O-linked glycosylation	197:226	dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins	197:274	O-GlcNAcylation is a kind of dynamic O-linked glycosylation of nucleocytoplasmic and mitochondrial proteins.
28254785	3	0	theme	epidermal	533:541	arg1	domains					568:574	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	1	theme	growth	543:548	arg1	domains					568:574	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	5	2	theme	Notch	997:1001	arg1	ligands					1003:1009	Notch ligands	997:1009	Notch ligands	997:1009	This mechanism enables cellular forces to regulate binding, discriminate among Notch ligands, and potentiate Notch signaling.
28254785	3	3	theme	EGF3	596:599	arg1	Jag1					619:622	Jag1	619:622	Jag1	619:622	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	3	theme	EGF3	596:599	arg1	domains					608:614	the EGF3 and C2 domains	592:614	domains	608:614	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	4	4	from	interactions	851:862	arg1	range					871:875	the range	867:875	the range of forces required for Notch activation	867:915	Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation.
28254785	2	5	theme	Notch1	312:317	arg1	region					302:307	the extracellular interacting region	272:307	the extracellular interacting region of Notch1	272:317	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	1	6	theme	cell	121:124	arg1	decisions					131:139	cell fate decisions	121:139	cell fate decisions	121:139	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	5	7	theme	cellular	941:948	arg1	forces					950:955	cellular forces	941:955	cellular forces	941:955	This mechanism enables cellular forces to regulate binding, discriminate among Notch ligands, and potentiate Notch signaling.
28254785	1	8	from	distinctive	148:158	arg1	reliance					167:174	its reliance	163:174	its reliance on mechanical force and protein glycosylation	163:220	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	3	9	theme	EGF	563:565	arg1	domains					568:574	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	2	10	theme	binding	399:405	arg1	interface					407:415	a binding interface	397:415	a binding interface that extends ~120 angstroms along five consecutive domains of each protein	397:490	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	11	theme	region	302:307	arg1	structure					259:267	The 2.5-angstrom-resolution crystal structure	223:267	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1)	223:387	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	0	12	theme	complex	13:19	arg1	structure					21:29	Notch-Jagged complex structure	0:29	Notch-Jagged complex structure	0:29	Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity.
28254785	3	13	theme	Delta-like	727:736	arg1	ligand					740:745	the Delta-like 4 ligand	723:745	the Delta-like 4 ligand	723:745	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	14	from	modifications	509:521	arg1	domains					568:574	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	1	15	theme	Notch	85:89	arg1	activation					100:109	Notch receptor activation	85:109	Notch receptor activation	85:109	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	0	16	from	bond	50:53	arg1	sensitivity					72:82	tuning ligand sensitivity	58:82	tuning ligand sensitivity	58:82	Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity.
28254785	1	17	theme	mechanical	179:188	arg1	force					190:194	mechanical force	179:194	mechanical force	179:194	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	0	18	theme	Notch-Jagged	0:11	arg1	structure					21:29	Notch-Jagged complex structure	0:29	Notch-Jagged complex structure	0:29	Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity.
28254785	1	19	theme	receptor	91:98	arg1	activation					100:109	Notch receptor activation	85:109	Notch receptor activation	85:109	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	2	20	theme	consecutive	456:466	arg1	domains					468:474	five consecutive domains	451:474	five consecutive domains of each protein	451:490	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	20	theme	consecutive	456:466	arg1	protein					484:490	each protein	479:490	each protein	479:490	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	4	21	theme	bond	823:826	arg1	behavior					828:835	catch bond behavior	817:835	catch bond behavior that prolongs interactions in the range of forces required for Notch activation	817:915	Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation.
28254785	2	22	theme	engineered	337:346	arg1	variant					363:369	an engineered, high-affinity variant	334:369	variant	363:369	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	4	23	theme	conformational	763:776	arg1	changes					778:784	conformational changes	763:784	conformational changes	763:784	Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation.
28254785	3	24	theme	different	643:651	arg1	domains					660:666	different Notch1 domains	643:666	different Notch1 domains	643:666	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	5	25	theme	Notch	1027:1031	arg1	signaling					1033:1041	Notch signaling	1027:1041	Notch signaling	1027:1041	This mechanism enables cellular forces to regulate binding, discriminate among Notch ligands, and potentiate Notch signaling.
28254785	1	26	theme	protein	200:206	arg1	glycosylation					208:220	protein glycosylation	200:220	protein glycosylation	200:220	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	0	27	theme	catch	44:48	arg1	bond					50:53	a catch bond	42:53	a catch bond in tuning ligand sensitivity	42:82	Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity.
28254785	3	28	theme	Notch1	526:531	arg1	domains					568:574	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	29	theme	Notch1	653:658	arg1	domains					660:666	different Notch1 domains	643:666	different Notch1 domains	643:666	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	30	theme	C2	605:606	arg1	Jag1					619:622	Jag1	619:622	Jag1	619:622	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	30	theme	C2	605:606	arg1	domains					608:614	the EGF3 and C2 domains	592:614	domains	608:614	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	2	31	theme	~120	430:433	arg1	angstroms					435:443	~120 angstroms	430:443	~120 angstroms	430:443	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	32	theme	crystal	251:257	arg1	structure					259:267	The 2.5-angstrom-resolution crystal structure	223:267	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1)	223:387	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	33	theme	protein	484:490	arg1	domains					468:474	five consecutive domains	451:474	five consecutive domains of each protein	451:490	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	33	theme	protein	484:490	arg1	protein					484:490	each protein	479:490	each protein	479:490	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	34	theme	2.5-angstrom-resolution	227:249	arg1	structure					259:267	The 2.5-angstrom-resolution crystal structure	223:267	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1)	223:387	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	35	theme	Jagged1	374:380	arg1	variant					363:369	an engineered, high-affinity variant	334:369	variant	363:369	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	4	36	theme	forces	880:885	arg1	range					871:875	the range	867:875	the range of forces required for Notch activation	867:915	Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation.
28254785	4	37	theme	catch	817:821	arg1	behavior					828:835	catch bond behavior	817:835	catch bond behavior that prolongs interactions in the range of forces required for Notch activation	817:915	Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation.
28254785	1	38	theme	fate	126:129	arg1	decisions					131:139	cell fate decisions	121:139	cell fate decisions	121:139	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	4	39	theme	Notch	791:795	arg1	binding					797:803	Notch binding	791:803	Notch binding	791:803	Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation.
28254785	4	40	theme	Notch	900:904	arg1	activation					906:915	Notch activation	900:915	Notch activation	900:915	Jag1 undergoes conformational changes upon Notch binding, exhibiting catch bond behavior that prolongs interactions in the range of forces required for Notch activation.
28254785	2	41	theme	interacting	290:300	arg1	region					302:307	the extracellular interacting region	272:307	the extracellular interacting region of Notch1	272:317	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	3	42	theme	fucose	502:507	arg1	modifications					509:521	O-Linked fucose modifications	493:521	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12	493:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	2	43	theme	extracellular	276:288	arg1	region					302:307	the extracellular interacting region	272:307	the extracellular interacting region of Notch1	272:317	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	2	44	theme	high-affinity	349:361	arg1	variant					363:369	an engineered, high-affinity variant	334:369	variant	363:369	The 2.5-angstrom-resolution crystal structure of the extracellular interacting region of Notch1 complexed with an engineered, high-affinity variant of Jagged1 (Jag1) reveals a binding interface that extends ~120 angstroms along five consecutive domains of each protein.
28254785	3	45	theme	O-Linked	493:500	arg1	modifications					509:521	O-Linked fucose modifications	493:521	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12	493:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	46	dep	domains	568:574	arg1	12					582:583	12	582:583	12	582:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	46	dep	domains	568:574	arg1	8					576:576	8	576:576	8	576:576	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	0	47	theme	ligand	65:70	arg1	sensitivity					72:82	tuning ligand sensitivity	58:82	tuning ligand sensitivity	58:82	Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity.
28254785	3	48	theme	factor-like	550:560	arg1	domains					568:574	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	Notch1 epidermal growth factor-like (EGF) domains 8 and 12	526:583	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	0	49	theme	tuning	58:63	arg1	sensitivity					72:82	tuning ligand sensitivity	58:82	tuning ligand sensitivity	58:82	Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity.
28254785	3	50	theme	Jag1	619:622	arg1	Jag1					619:622	Jag1	619:622	Jag1	619:622	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	3	50	theme	Jag1	619:622	arg1	domains					608:614	the EGF3 and C2 domains	592:614	domains	608:614	O-Linked fucose modifications on Notch1 epidermal growth factor-like (EGF) domains 8 and 12 engage the EGF3 and C2 domains of Jag1, respectively, and different Notch1 domains are favored in binding to Jag1 than those that bind to the Delta-like 4 ligand.
28254785	1	51	from	reliance	167:174	arg1	distinctive					148:158	distinctive	148:158	distinctive	148:158	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	1	51	from	reliance	167:174	arg1	force					190:194	mechanical force	179:194	mechanical force	179:194	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28254785	1	51	from	reliance	167:174	arg1	glycosylation					208:220	protein glycosylation	200:220	protein glycosylation	200:220	Notch receptor activation initiates cell fate decisions and is distinctive in its reliance on mechanical force and protein glycosylation.
28178567	2	0	theme	ischemic	483:490	arg1	injury					492:497	ischemic injury	483:497	ischemic injury	483:497	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	2	1	theme	knockout	365:372	arg1	catabolism					353:362	impaired BCAA catabolism	339:362	impaired BCAA catabolism (knockout [KO])	339:378	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	2	1	theme	knockout	365:372	arg1	[KO					374:376	knockout [KO	365:376	knockout [KO	365:376	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	1	2	theme	diseases	267:274	arg1	development					223:233	the development	219:233	the development of cardiovascular and metabolic diseases	219:274	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	0	3	theme	Ischemia-Reperfusion	103:122	arg1	Injury					124:129	Ischemia-Reperfusion Injury	103:129	Ischemia-Reperfusion Injury	103:129	Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury.
28178567	3	4	theme	mitochondrial	543:555	arg1	utilization					566:576	mitochondrial pyruvate utilization	543:576	mitochondrial pyruvate utilization	543:576	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	3	5	theme	pyruvate	557:564	arg1	utilization					566:576	mitochondrial pyruvate utilization	543:576	mitochondrial pyruvate utilization	543:576	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	4	6	theme	N-acetylglucosamine	754:772	arg1	modification					785:796	protein O-linked N-acetylglucosamine (O-GlcNAc) modification	737:796	protein O-linked N-acetylglucosamine (O-GlcNAc) modification	737:796	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	1	7	theme	Elevated	132:139	arg1	levels					141:146	Elevated levels	132:146	Elevated levels of branched-chain amino acids (BCAAs)	132:184	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	6	8	theme	functional	1164:1173	arg1	outcome					1175:1181	the metabolic and functional outcome	1146:1181	the metabolic and functional outcome	1146:1181	Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome.
28178567	5	9	theme	metabolic	889:897	arg1	remodeling					899:908	the metabolic remodeling	885:908	the metabolic remodeling in KO	885:914	Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury.
28178567	4	10	link	O-linked	745:752	arg1	O-GlcNAc					775:782	O-GlcNAc	775:782	O-GlcNAc	775:782	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	4	10	link	O-linked	745:752	arg1	N-acetylglucosamine					754:772	protein O-linked N-acetylglucosamine	737:772	protein O-linked N-acetylglucosamine (O-GlcNAc) modification	737:796	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	4	11	theme	hexosamine	682:691	arg1	pathway					706:712	the hexosamine biosynthetic pathway	678:712	the hexosamine biosynthetic pathway	678:712	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	6	12	theme	BCAA	1047:1050	arg1	catabolism					1052:1061	BCAA catabolism	1047:1061	BCAA catabolism	1047:1061	Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome.
28178567	6	13	theme	normalizing	1066:1076	arg1	utilization					1086:1096	normalizing glucose utilization	1066:1096	normalizing glucose utilization	1066:1096	Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome.
28178567	7	14	theme	stress	1281:1286	arg1	response					1288:1295	stress response	1281:1295	stress response	1281:1295	These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.
28178567	0	15	theme	Defective	0:8	arg1	Catabolism					36:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury.
28178567	0	16	theme	Branched-Chain	10:23	arg1	Catabolism					36:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury.
28178567	3	17	theme	BCAAs	515:519	arg1	levels					505:510	High levels	500:510	High levels of BCAAs	500:519	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	4	18	theme	pathway	706:712	arg1	downregulation					660:673	downregulation	660:673	downregulation of the hexosamine biosynthetic pathway in KO hearts	660:725	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	2	19	theme	glucose	436:442	arg1	metabolism					444:453	glucose metabolism	436:453	glucose metabolism	436:453	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	1	20	theme	molecular	285:293	arg1	unknown					310:316	unknown	310:316	unknown	310:316	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	1	20	theme	molecular	285:293	arg1	mechanisms					295:304	the molecular mechanisms	281:304	the molecular mechanisms	281:304	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	2	21	theme	a mouse	322:328	arg1	model					330:334	a mouse model	322:334	a mouse model of impaired BCAA catabolism (knockout [KO])	322:378	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	4	22	theme	biosynthetic	693:704	arg1	pathway					706:712	the hexosamine biosynthetic pathway	678:712	the hexosamine biosynthetic pathway	678:712	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	0	23	theme	Acid	31:34	arg1	Catabolism					36:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury.
28178567	6	24	theme	glucose	1078:1084	arg1	utilization					1086:1096	normalizing glucose utilization	1066:1096	normalizing glucose utilization	1066:1096	Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome.
28178567	4	25	from	downregulation	660:673	arg1	hearts					720:725	KO hearts	717:725	KO hearts	717:725	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	6	26	theme	KO	1129:1130	arg1	heart					1132:1136	the KO heart	1125:1136	the KO heart	1125:1136	Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome.
28178567	2	27	theme	BCAAs	419:423	arg1	accumulation					403:414	chronic accumulation	395:414	chronic accumulation of BCAAs	395:423	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	4	28	theme	KO	717:718	arg1	hearts					720:725	KO hearts	717:725	KO hearts	717:725	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	3	29	theme	High	500:503	arg1	levels					505:510	High levels	500:510	High levels of BCAAs	500:519	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	4	30	theme	protein	737:743	arg1	O-GlcNAc					775:782	O-GlcNAc	775:782	O-GlcNAc	775:782	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	4	30	theme	protein	737:743	arg1	N-acetylglucosamine					754:772	protein O-linked N-acetylglucosamine	737:772	protein O-linked N-acetylglucosamine (O-GlcNAc) modification	737:796	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	7	31	theme	cardiac	1258:1264	arg1	metabolism					1266:1275	cardiac metabolism	1258:1275	cardiac metabolism	1258:1275	These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.
28178567	3	32	theme	complex	623:629	arg1	activity					637:644	pyruvate dehydrogenase complex (PDH) activity	600:644	pyruvate dehydrogenase complex (PDH) activity	600:644	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	2	33	theme	chronic	395:401	arg1	accumulation					403:414	chronic accumulation	395:414	chronic accumulation of BCAAs	395:423	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	6	34	theme	metabolic	1150:1158	arg1	outcome					1175:1181	the metabolic and functional outcome	1146:1181	the metabolic and functional outcome	1146:1181	Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome.
28178567	7	35	theme	BCAA	1228:1231	arg1	catabolism					1233:1242	BCAA catabolism	1228:1242	BCAA catabolism	1228:1242	These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.
28178567	4	36	theme	glucose	857:863	arg1	oxidation					865:873	glucose oxidation	857:873	glucose oxidation	857:873	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	5	37	from	remodeling	899:908	arg1	KO					913:914	KO	913:914	KO	913:914	Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury.
28178567	7	38	theme	novel	1214:1218	arg1	role					1220:1223	a novel role	1212:1223	a novel role of BCAA catabolism in regulating cardiac metabolism and stress response	1212:1295	These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.
28178567	5	39	theme	baseline	931:938	arg1	energetics					948:957	baseline cardiac energetics	931:957	baseline cardiac energetics	931:957	Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury.
28178567	3	40	theme	pyruvate	600:607	arg1	complex					623:629	pyruvate dehydrogenase complex	600:629	pyruvate dehydrogenase complex (PDH) activity	600:644	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	3	40	theme	pyruvate	600:607	arg1	PDH					632:634	PDH	632:634	PDH	632:634	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	2	41	theme	catabolism	353:362	arg1	model					330:334	a mouse model	322:334	a mouse model of impaired BCAA catabolism (knockout [KO])	322:378	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	0	42	theme	Glucose	56:62	arg1	Metabolism					64:73	Glucose Metabolism	56:73	Glucose Metabolism	56:73	Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury.
28178567	3	43	theme	dehydrogenase	609:621	arg1	complex					623:629	pyruvate dehydrogenase complex	600:629	pyruvate dehydrogenase complex (PDH) activity	600:644	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	3	43	theme	dehydrogenase	609:621	arg1	PDH					632:634	PDH	632:634	PDH	632:634	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	2	44	theme	BCAA	348:351	arg1	catabolism					353:362	impaired BCAA catabolism	339:362	impaired BCAA catabolism (knockout [KO])	339:378	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	2	44	theme	BCAA	348:351	arg1	[KO					374:376	knockout [KO	365:376	knockout [KO	365:376	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	7	45	theme	catabolism	1233:1242	arg1	role					1220:1223	a novel role	1212:1223	a novel role of BCAA catabolism in regulating cardiac metabolism and stress response	1212:1295	These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.
28178567	4	46	theme	O-linked	745:752	arg1	O-GlcNAc					775:782	O-GlcNAc	775:782	O-GlcNAc	775:782	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	4	46	theme	O-linked	745:752	arg1	N-acetylglucosamine					754:772	protein O-linked N-acetylglucosamine	737:772	protein O-linked N-acetylglucosamine (O-GlcNAc) modification	737:796	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	4	47	theme	significant	832:842	arg1	decreases					844:852	significant decreases	832:852	significant decreases in glucose oxidation	832:873	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	3	48	theme	activity	637:644	arg1	inhibition					586:595	inhibition	586:595	inhibition of pyruvate dehydrogenase complex (PDH) activity	586:644	High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity.
28178567	2	49	theme	impaired	339:346	arg1	catabolism					353:362	impaired BCAA catabolism	339:362	impaired BCAA catabolism (knockout [KO])	339:378	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	2	49	theme	impaired	339:346	arg1	[KO					374:376	knockout [KO	365:376	knockout [KO	365:376	In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury.
28178567	5	50	theme	ischemia-reperfusion	1008:1027	arg1	injury					1029:1034	ischemia-reperfusion injury	1008:1034	ischemia-reperfusion injury	1008:1034	Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury.
28178567	1	51	theme	branched-chain	151:164	arg1	acids					172:176	branched-chain amino acids	151:176	branched-chain amino acids (BCAAs)	151:184	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	1	51	theme	branched-chain	151:164	arg1	BCAAs					179:183	BCAAs	179:183	BCAAs	179:183	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	1	52	theme	cardiovascular	238:251	arg1	diseases					267:274	cardiovascular and metabolic diseases	238:274	cardiovascular and metabolic diseases	238:274	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	5	53	theme	cardiac	940:946	arg1	energetics					948:957	baseline cardiac energetics	931:957	baseline cardiac energetics	931:957	Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury.
28178567	4	54	from	decreases	844:852	arg1	oxidation					865:873	glucose oxidation	857:873	glucose oxidation	857:873	Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation.
28178567	1	55	theme	amino	166:170	arg1	acids					172:176	branched-chain amino acids	151:176	branched-chain amino acids (BCAAs)	151:184	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	1	55	theme	amino	166:170	arg1	BCAAs					179:183	BCAAs	179:183	BCAAs	179:183	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	0	56	theme	Amino	25:29	arg1	Catabolism					36:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism	0:45	Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury.
28178567	1	57	theme	acids	172:176	arg1	levels					141:146	Elevated levels	132:146	Elevated levels of branched-chain amino acids (BCAAs)	132:184	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
28178567	1	58	theme	metabolic	257:265	arg1	diseases					267:274	cardiovascular and metabolic diseases	238:274	cardiovascular and metabolic diseases	238:274	Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown.
31685298	0	0	theme	ovarian	81:87	arg1	cancer					89:94	serous ovarian cancer	74:94	serous ovarian cancer	74:94	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	0	1	theme	β-catenin	182:190	arg1	location					170:177	the nuclear location	158:177	the nuclear location of β-catenin	158:190	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	2	2	theme	first	475:479	arg1	HBP					464:466	the HBP	460:466	the HBP	460:466	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme.
31685298	2	2	theme	first	475:479	arg1	enzyme					499:504	the first and rate-limiting enzyme	471:504	the first and rate-limiting enzyme	471:504	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme.
31685298	3	3	from	mechanisms	735:744	arg1	SOC					749:751	SOC	749:751	SOC	749:751	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	6	4	from	increase	1159:1166	arg1	O-GlcNAcylation					1171:1185	O-GlcNAcylation	1171:1185	O-GlcNAcylation	1171:1185	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	4	5	theme	positive	823:830	arg1	correlations					832:843	positive correlations	823:843	positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival	823:920	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	1	6	theme	wide-ranging	333:344	arg1	effect					346:351	a wide-ranging effect	331:351	a wide-ranging effect on cellular functions	331:373	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	3	7	theme	GFPT2	545:549	arg1	expression					551:560	GFPT2 expression	545:560	GFPT2 expression	545:560	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	1	8	theme	glucose	248:254	arg1	metabolism					256:265	glucose metabolism	248:265	glucose metabolism	248:265	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	0	9	theme	cancer	89:94	arg1	EMT					67:69	the EMT	63:69	the EMT of serous ovarian cancer	63:94	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	5	10	theme	HEY	1033:1035	arg1	cells					1037:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells.
31685298	6	11	theme	epithelial-mesenchymal	1222:1243	arg1	transition					1245:1254	epithelial-mesenchymal transition	1222:1254	epithelial-mesenchymal transition (EMT)	1222:1260	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	6	11	theme	epithelial-mesenchymal	1222:1243	arg1	EMT					1257:1259	EMT	1257:1259	EMT	1257:1259	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	1	12	theme	metabolism	256:265	arg1	pathway					221:227	The hexosamine biosynthetic pathway	193:227	The hexosamine biosynthetic pathway (HBP)	193:233	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	1	12	theme	metabolism	256:265	arg1	branch					238:243	a branch	236:243	a branch of glucose metabolism	236:265	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	4	13	theme	poor	908:911	arg1	survival					913:920	poor survival	908:920	poor survival	908:920	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	4	14	theme	SOC	806:808	arg1	tissues					810:816	SOC tissues	806:816	SOC tissues	806:816	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	6	15	theme	β-catenin	1117:1125	arg1	levels					1048:1053	The levels	1044:1053	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin	1044:1125	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	7	16	from	function	1306:1313	arg1	EMT					1351:1353	the EMT	1347:1353	the EMT	1347:1353	These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.
31685298	1	17	theme	cellular	356:363	arg1	functions					365:373	cellular functions	356:373	cellular functions	356:373	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	6	18	theme	intranuclear	1104:1115	arg1	β-catenin					1117:1125	intranuclear β-catenin	1104:1125	intranuclear β-catenin	1104:1125	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	0	19	theme	serous	74:79	arg1	cancer					89:94	serous ovarian cancer	74:94	serous ovarian cancer	74:94	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	2	20	theme	Glutamine-fructose-6-phosphate	376:405	arg1	transaminase					407:418	Glutamine-fructose-6-phosphate transaminase 2	376:420	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2)	376:428	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme.
31685298	2	20	theme	Glutamine-fructose-6-phosphate	376:405	arg1	GFPT2					423:427	GFPT2	423:427	GFPT2	423:427	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme.
31685298	0	21	theme	Glutamine-fructose-6-phosphate	0:29	arg1	transaminase					31:42	Glutamine-fructose-6-phosphate transaminase 2	0:44	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2)	0:52	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	0	21	theme	Glutamine-fructose-6-phosphate	0:29	arg1	GFPT2					47:51	GFPT2	47:51	GFPT2	47:51	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	3	22	theme	patients	578:585	arg1	survival					566:573	survival	566:573	survival	566:573	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	22	theme	patients	578:585	arg1	expression					551:560	GFPT2 expression	545:560	GFPT2 expression	545:560	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	7	23	theme	GFPT2	1318:1322	arg1	function					1306:1313	the function	1302:1313	the function of GFPT2 and O-GlcNAcylation in the EMT	1302:1353	These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.
31685298	5	24	theme	knockdown	1013:1021	arg1	cells					1037:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells.
31685298	1	25	from	effect	346:351	arg1	functions					365:373	cellular functions	356:373	cellular functions	356:373	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	0	26	theme	biosynthetic	125:136	arg1	pathway					138:144	the hexosamine biosynthetic pathway	110:144	the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin	110:190	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	7	27	theme	O-GlcNAcylation	1328:1342	arg1	function					1306:1313	the function	1302:1313	the function of GFPT2 and O-GlcNAcylation in the EMT	1302:1353	These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.
31685298	5	28	theme	Cell	956:959	arg1	migration					961:969	Cell migration	956:969	Cell migration	956:969	Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells.
31685298	1	29	theme	hexosamine	197:206	arg1	HBP					230:232	HBP	230:232	HBP	230:232	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	1	29	theme	hexosamine	197:206	arg1	pathway					221:227	The hexosamine biosynthetic pathway	193:227	The hexosamine biosynthetic pathway (HBP)	193:233	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	1	29	theme	hexosamine	197:206	arg1	branch					238:243	a branch	236:243	a branch of glucose metabolism	236:265	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	3	30	from	role	705:708	arg1	SOC					749:751	SOC	749:751	SOC	749:751	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	0	31	theme	hexosamine	114:123	arg1	pathway					138:144	the hexosamine biosynthetic pathway	110:144	the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin	110:190	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	3	32	theme	Cancer	636:641	arg1	database					663:670	The Cancer Genome Atlas (TCGA) database	632:670	The Cancer Genome Atlas (TCGA) database	632:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	1	33	theme	biosynthetic	208:219	arg1	HBP					230:232	HBP	230:232	HBP	230:232	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	1	33	theme	biosynthetic	208:219	arg1	pathway					221:227	The hexosamine biosynthetic pathway	193:227	The hexosamine biosynthetic pathway (HBP)	193:233	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	1	33	theme	biosynthetic	208:219	arg1	branch					238:243	a branch	236:243	a branch of glucose metabolism	236:265	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	4	34	theme	SOC	942:944	arg1	patients					946:953	90 SOC patients	939:953	90 SOC patients	939:953	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	3	35	theme	GFPT2	713:717	arg1	mechanisms					735:744	its related mechanisms	723:744	its related mechanisms in SOC	723:751	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	35	theme	GFPT2	713:717	arg1	role					705:708	the role	701:708	the role of GFPT2	701:717	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	4	36	theme	suboptimal	880:889	arg1	rate					899:902	suboptimal removal rate	880:902	suboptimal removal rate	880:902	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	3	37	theme	Genome	643:648	arg1	database					663:670	The Cancer Genome Atlas (TCGA) database	632:670	The Cancer Genome Atlas (TCGA) database	632:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	38	theme	ovarian	599:605	arg1	SOC					615:617	SOC	615:617	SOC	615:617	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	38	theme	ovarian	599:605	arg1	cancer					607:612	serous ovarian cancer	592:612	serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database	592:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	7	39	theme	novel	1282:1286	arg1	insights					1288:1295	novel insights	1282:1295	novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT	1282:1353	These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.
31685298	5	40	theme	SKOV3	1023:1027	arg1	cells					1037:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells.
31685298	5	41	theme	GFPT2	1007:1011	arg1	cells					1037:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	GFPT2 knockdown SKOV3 and HEY cells	1007:1041	Cell migration and invasion were also inhibited in GFPT2 knockdown SKOV3 and HEY cells.
31685298	1	42	theme	glycosylation	293:305	arg1	modification					307:318	glycosylation modification	293:318	glycosylation modification	293:318	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	6	43	link	O-linked	1058:1065	arg1	O-GlcNAc					1090:1097	O-GlcNAc	1090:1097	O-GlcNAc	1090:1097	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	6	43	link	O-linked	1058:1065	arg1	β-N-acetylglucosamine					1067:1087	O-linked β-N-acetylglucosamine	1058:1087	O-linked β-N-acetylglucosamine (O-GlcNAc)	1058:1098	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	6	44	theme	β-N-acetylglucosamine	1067:1087	arg1	levels					1048:1053	The levels	1044:1053	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin	1044:1125	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	3	45	theme	related	727:733	arg1	mechanisms					735:744	its related mechanisms	723:744	its related mechanisms in SOC	723:751	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	4	46	theme	advanced	850:857	arg1	stage					859:863	advanced stage	850:863	advanced stage (FIGO III/IV)	850:877	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	4	46	theme	advanced	850:857	arg1	III/IV					871:876	FIGO III/IV	866:876	FIGO III/IV	866:876	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	3	47	theme	TCGA	657:660	arg1	database					663:670	The Cancer Genome Atlas (TCGA) database	632:670	The Cancer Genome Atlas (TCGA) database	632:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	48	theme	serous	592:597	arg1	SOC					615:617	SOC	615:617	SOC	615:617	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	48	theme	serous	592:597	arg1	cancer					607:612	serous ovarian cancer	592:612	serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database	592:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	4	49	located	observed	927:934	arg1	patients					946:953	90 SOC patients	939:953	90 SOC patients	939:953	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	4	49	located	observed	927:934	arg2	correlations					832:843	positive correlations	823:843	positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival	823:920	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	6	50	theme	O-linked	1058:1065	arg1	O-GlcNAc					1090:1097	O-GlcNAc	1090:1097	O-GlcNAc	1090:1097	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	6	50	theme	O-linked	1058:1065	arg1	β-N-acetylglucosamine					1067:1087	O-linked β-N-acetylglucosamine	1058:1087	O-linked β-N-acetylglucosamine (O-GlcNAc)	1058:1098	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	3	51	located	observed	620:627	arg1	database					663:670	The Cancer Genome Atlas (TCGA) database	632:670	The Cancer Genome Atlas (TCGA) database	632:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	51	located	observed	620:627	arg2	cancer					607:612	serous ovarian cancer	592:612	serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database	592:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	51	located	observed	620:627	arg2	SOC					615:617	SOC	615:617	SOC	615:617	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	4	52	theme	FIGO	866:869	arg1	stage					859:863	advanced stage	850:863	advanced stage (FIGO III/IV)	850:877	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	4	52	theme	FIGO	866:869	arg1	III/IV					871:876	FIGO III/IV	866:876	FIGO III/IV	866:876	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	7	53	theme	invasiveness	1368:1379	arg1	SOC					1381:1383	the invasiveness SOC	1364:1383	the invasiveness SOC	1364:1383	These data provide novel insights into the function of GFPT2 and O-GlcNAcylation in the EMT and thus the invasiveness SOC.
31685298	1	54	contain	has	327:329	arg1	substrate					279:287	a substrate	277:287	a substrate	277:287	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	1	54	contain	has	327:329	arg2	effect					346:351	a wide-ranging effect	331:351	a wide-ranging effect on cellular functions	331:373	The hexosamine biosynthetic pathway (HBP), a branch of glucose metabolism, provides a substrate for glycosylation modification, which has a wide-ranging effect on cellular functions.
31685298	4	55	with	correlations	832:843	arg1	III/IV					871:876	FIGO III/IV	866:876	FIGO III/IV	866:876	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	4	55	with	correlations	832:843	arg1	stage					859:863	advanced stage	850:863	advanced stage (FIGO III/IV)	850:877	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	4	55	with	correlations	832:843	arg1	survival					913:920	poor survival	908:920	poor survival	908:920	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	4	55	with	correlations	832:843	arg1	rate					899:902	suboptimal removal rate	880:902	suboptimal removal rate	880:902	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
31685298	0	56	theme	nuclear	162:168	arg1	location					170:177	the nuclear location	158:177	the nuclear location of β-catenin	158:190	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) promotes the EMT of serous ovarian cancer by activating the hexosamine biosynthetic pathway to increase the nuclear location of β-catenin.
31685298	3	57	theme	Atlas	650:654	arg1	database					663:670	The Cancer Genome Atlas (TCGA) database	632:670	The Cancer Genome Atlas (TCGA) database	632:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	6	58	theme	observed	1150:1157	arg1	increase					1159:1166	the observed increase	1146:1166	the observed increase in O-GlcNAcylation induced by GFPT2	1146:1202	The levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and intranuclear β-catenin were evaluated and the observed increase in O-GlcNAcylation induced by GFPT2 may contribute to epithelial-mesenchymal transition (EMT).
31685298	2	59	theme	rate-limiting	485:497	arg1	HBP					464:466	the HBP	460:466	the HBP	460:466	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme.
31685298	2	59	theme	rate-limiting	485:497	arg1	enzyme					499:504	the first and rate-limiting enzyme	471:504	the first and rate-limiting enzyme	471:504	Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) has been reported to regulate the HBP as the first and rate-limiting enzyme.
31685298	3	60	with	patients	578:585	arg1	SOC					615:617	SOC	615:617	SOC	615:617	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	60	with	patients	578:585	arg1	cancer					607:612	serous ovarian cancer	592:612	serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database	592:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	3	61	theme	inverse	517:523	arg1	association					525:535	the inverse association	513:535	the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database	513:670	Given the inverse association between GFPT2 expression and survival of patients with serous ovarian cancer (SOC) observed in The Cancer Genome Atlas (TCGA) database, we attempted to investigate the role of GFPT2 and its related mechanisms in SOC.
31685298	4	62	theme	removal	891:897	arg1	rate					899:902	suboptimal removal rate	880:902	suboptimal removal rate	880:902	The results showed that GFPT2 was over-expressed in SOC tissues, and positive correlations with advanced stage (FIGO III/IV), suboptimal removal rate and poor survival were observed in 90 SOC patients.
30017190	5	0	theme	similar	769:775	arg1	retinas					760:766	diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	745:884	retinas	760:766	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	8	1	theme	cleaved	1521:1527	arg1	caspase-3					1529:1537	pro-apoptotic marker cleaved caspase-3	1500:1537	pro-apoptotic marker cleaved caspase-3	1500:1537	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	5	2	theme	carboxylase	639:649	arg1	activation					574:583	the decreased activation	560:583	the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase	560:649	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	8	3	theme	ADP-ribose	1473:1482	arg1	polymerase					1485:1494	cleaved poly(ADP-ribose) polymerase	1460:1494	cleaved poly(ADP-ribose) polymerase	1460:1494	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	6	4	theme	cells	1096:1100	arg1	treatment					1079:1087	metformin treatment	1069:1087	metformin treatment of RPE cells	1069:1100	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	6	5	link	O-linked	924:931	arg1	OGT					968:970	OGT	968:970	OGT	968:970	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	6	5	link	O-linked	924:931	arg1	transferase					955:965	O-linked β-N-acetylglucosamine transferase	924:965	O-linked β-N-acetylglucosamine transferase (OGT)	924:971	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	8	6	theme	diabetic	1542:1549	arg1	retinas					1551:1557	diabetic retinas	1542:1557	diabetic retinas	1542:1557	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	5	7	theme	AMP-activated	588:600	arg1	AMPK					618:621	AMPK	618:621	AMPK	618:621	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	5	7	theme	AMP-activated	588:600	arg1	kinase					610:615	AMP-activated protein kinase	588:615	AMP-activated protein kinase (AMPK)	588:622	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	6	8	theme	RPE	1092:1094	arg1	cells					1096:1100	RPE cells	1092:1100	RPE cells	1092:1100	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	5	9	theme	sirtuin3	733:740	arg1	levels					670:675	the levels	666:675	the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	666:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	7	10	theme	retinal	1395:1401	arg1	cells					1412:1416	retinal ganglion cells	1395:1416	retinal ganglion cells	1395:1416	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	5	11	theme	protein	602:608	arg1	AMPK					618:621	AMPK	618:621	AMPK	618:621	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	5	11	theme	protein	602:608	arg1	kinase					610:615	AMP-activated protein kinase	588:615	AMP-activated protein kinase (AMPK)	588:622	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	6	12	theme	protein	1001:1007	arg1	levels					914:919	the levels	910:919	the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP)	910:1015	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	8	13	theme	pro-apoptotic	1500:1512	arg1	caspase-3					1529:1537	pro-apoptotic marker cleaved caspase-3	1500:1537	pro-apoptotic marker cleaved caspase-3	1500:1537	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	4	14	theme	glutathione	459:469	arg1	peroxidase					471:480	glutathione peroxidase	459:480	glutathione peroxidase	459:480	We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death.
30017190	5	15	theme	kinase	610:615	arg1	activation					574:583	the decreased activation	560:583	the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase	560:649	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	2	16	theme	diabetic	248:255	arg1	mice					257:260	diabetic mice	248:260	diabetic mice	248:260	Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice.
30017190	7	17	from	OGT	1379:1381	arg1	cells					1412:1416	retinal ganglion cells	1395:1416	retinal ganglion cells	1395:1416	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	6	18	theme	thioredoxin-interacting	977:999	arg1	TXNIP					1010:1014	TXNIP	1010:1014	TXNIP	1010:1014	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	6	18	theme	thioredoxin-interacting	977:999	arg1	protein					1001:1007	thioredoxin-interacting protein	977:1007	thioredoxin-interacting protein (TXNIP)	977:1015	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	5	19	theme	diabetic	745:752	arg1	retinas					760:766	diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	745:884	retinas	760:766	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	8	20	theme	polymerase	1485:1494	arg1	levels					1450:1455	the levels	1446:1455	the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3	1446:1537	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	7	21	theme	transferase-mediated	1330:1349	arg1	labelling					1365:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	1	22	theme	Oxidative	63:71	arg1	stress					73:78	Oxidative stress	63:78	Oxidative stress	63:78	Oxidative stress plays an important role in the development of diabetic retinopathy.
30017190	7	23	theme	dUTP	1351:1354	arg1	labelling					1365:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	5	24	theme	mouse	754:758	arg1	retinas					760:766	diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	745:884	retinas	760:766	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	9	25	theme	OGT	1653:1655	arg1	inhibition					1657:1666	OGT inhibition	1653:1666	OGT inhibition	1653:1666	Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.
30017190	7	26	theme	co-immunoprecipitation	1175:1196	arg1	analyses					1198:1205	co-immunoprecipitation analyses	1175:1205	co-immunoprecipitation analyses	1175:1205	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	7	27	from	TXNIP	1386:1390	arg1	cells					1412:1416	retinal ganglion cells	1395:1416	retinal ganglion cells	1395:1416	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	5	28	theme	decreased	564:572	arg1	activation					574:583	the decreased activation	560:583	the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase	560:649	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	9	29	theme	retinal	1600:1606	arg1	death					1613:1617	retinal cell death	1600:1617	retinal cell death	1600:1617	Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.
30017190	9	30	from	inhibition	1657:1666	arg1	mice					1680:1683	diabetic mice	1671:1683	diabetic mice	1671:1683	Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.
30017190	6	31	theme	metformin	1069:1077	arg1	treatment					1079:1087	metformin treatment	1069:1087	metformin treatment of RPE cells	1069:1100	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	0	32	theme	Alpha-lipoic	0:11	arg1	acid					13:16	Alpha-lipoic acid	0:16	Alpha-lipoic acid	0:16	Alpha-lipoic acid reduces retinal cell death in diabetic mice.
30017190	5	33	theme	acetyl-CoA	628:637	arg1	carboxylase					639:649	acetyl-CoA carboxylase	628:649	acetyl-CoA carboxylase	628:649	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	9	34	theme	cell	1608:1611	arg1	death					1613:1617	retinal cell death	1600:1617	retinal cell death	1600:1617	Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.
30017190	9	35	from	activation	1639:1648	arg1	mice					1680:1683	diabetic mice	1671:1683	diabetic mice	1671:1683	Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.
30017190	5	36	theme	high	873:876	arg1	glucose					878:884	high glucose	873:884	high glucose	873:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	3	37	theme	streptozotocin-induced	325:346	arg1	diabetes					348:355	streptozotocin-induced diabetes	325:355	streptozotocin-induced diabetes	325:355	The α-LA was orally administered to control mice or mice with streptozotocin-induced diabetes.
30017190	5	38	theme	proliferator-activated	691:712	arg1	delta					723:727	peroxisome proliferator-activated receptor delta	680:727	peroxisome proliferator-activated receptor delta	680:727	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	1	39	theme	important	89:97	arg1	role					99:102	an important role	86:102	an important role	86:102	Oxidative stress plays an important role in the development of diabetic retinopathy.
30017190	2	40	theme	natural	198:204	arg1	acid					183:186	α-lipoic acid	174:186	α-lipoic acid (α-LA)	174:193	Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice.
30017190	2	40	theme	natural	198:204	arg1	antioxidant					206:216	a natural antioxidant	196:216	a natural antioxidant	196:216	Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice.
30017190	5	41	theme	epithelial	839:848	arg1	RPE					857:859	RPE	857:859	RPE	857:859	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	5	41	theme	epithelial	839:848	arg1	cells					850:854	retinal pigment epithelial cells	823:854	retinal pigment epithelial cells (RPE) exposed to high glucose	823:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	5	42	theme	pigment	831:837	arg1	RPE					857:859	RPE	857:859	RPE	857:859	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	5	42	theme	pigment	831:837	arg1	cells					850:854	retinal pigment epithelial cells	823:854	retinal pigment epithelial cells (RPE) exposed to high glucose	823:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	5	43	theme	receptor	714:721	arg1	delta					723:727	peroxisome proliferator-activated receptor delta	680:727	peroxisome proliferator-activated receptor delta	680:727	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	4	44	theme	increased	417:425	arg1	4-hydroxy-2-nonenal					435:453	increased retinal 4-hydroxy-2-nonenal	417:453	increased retinal 4-hydroxy-2-nonenal	417:453	We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death.
30017190	7	45	theme	cell	1241:1244	arg1	death					1246:1250	less cell death	1236:1250	less cell death	1236:1250	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	5	46	theme	cells	850:854	arg1	treatment					810:818	metformin treatment	800:818	metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	800:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	7	47	theme	terminal	1305:1312	arg1	labelling					1365:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	5	48	theme	delta	723:727	arg1	levels					670:675	the levels	666:675	the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	666:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	8	49	theme	poly	1468:1471	arg1	polymerase					1485:1494	cleaved poly(ADP-ribose) polymerase	1460:1494	cleaved poly(ADP-ribose) polymerase	1460:1494	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	3	50	with	mice	307:310	arg1	diabetes					348:355	streptozotocin-induced diabetes	325:355	streptozotocin-induced diabetes	325:355	The α-LA was orally administered to control mice or mice with streptozotocin-induced diabetes.
30017190	7	51	theme	nick-end	1356:1363	arg1	labelling					1365:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	0	52	theme	cell	34:37	arg1	death					39:43	retinal cell death	26:43	retinal cell death	26:43	Alpha-lipoic acid reduces retinal cell death in diabetic mice.
30017190	4	53	theme	cell	519:522	arg1	death					524:528	retinal cell death	511:528	retinal cell death	511:528	We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death.
30017190	0	54	theme	retinal	26:32	arg1	death					39:43	retinal cell death	26:43	retinal cell death	26:43	Alpha-lipoic acid reduces retinal cell death in diabetic mice.
30017190	5	55	theme	retinal	823:829	arg1	RPE					857:859	RPE	857:859	RPE	857:859	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	5	55	theme	retinal	823:829	arg1	cells					850:854	retinal pigment epithelial cells	823:854	retinal pigment epithelial cells (RPE) exposed to high glucose	823:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	0	56	theme	diabetic	48:55	arg1	mice					57:60	diabetic mice	48:60	diabetic mice	48:60	Alpha-lipoic acid reduces retinal cell death in diabetic mice.
30017190	4	57	theme	retinal	511:517	arg1	death					524:528	retinal cell death	511:528	retinal cell death	511:528	We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death.
30017190	4	58	theme	retinal	427:433	arg1	4-hydroxy-2-nonenal					435:453	increased retinal 4-hydroxy-2-nonenal	417:453	increased retinal 4-hydroxy-2-nonenal	417:453	We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death.
30017190	3	59	with	mice	315:318	arg1	diabetes					348:355	streptozotocin-induced diabetes	325:355	streptozotocin-induced diabetes	325:355	The α-LA was orally administered to control mice or mice with streptozotocin-induced diabetes.
30017190	7	60	theme	immunofluorescence	1274:1291	arg1	staining					1293:1300	double immunofluorescence staining	1267:1300	double immunofluorescence staining	1267:1300	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	5	61	theme	metformin	800:808	arg1	treatment					810:818	metformin treatment	800:818	metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	800:884	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	6	62	theme	O-linked	924:931	arg1	OGT					968:970	OGT	968:970	OGT	968:970	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	6	62	theme	O-linked	924:931	arg1	transferase					955:965	O-linked β-N-acetylglucosamine transferase	924:965	O-linked β-N-acetylglucosamine transferase (OGT)	924:971	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	7	63	theme	ganglion	1403:1410	arg1	cells					1412:1416	retinal ganglion cells	1395:1416	retinal ganglion cells	1395:1416	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	6	64	theme	transferase	955:965	arg1	levels					914:919	the levels	910:919	the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP)	910:1015	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	4	65	theme	oxidative	385:393	arg1	stress					395:400	oxidative stress	385:400	oxidative stress	385:400	We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death.
30017190	2	66	theme	retinal	230:236	arg1	injury					238:243	retinal injury	230:243	retinal injury	230:243	Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice.
30017190	9	67	theme	AMPK	1634:1637	arg1	activation					1639:1648	AMPK activation	1634:1648	AMPK activation	1634:1648	Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.
30017190	5	68	theme	peroxisome	680:689	arg1	delta					723:727	peroxisome proliferator-activated receptor delta	680:727	peroxisome proliferator-activated receptor delta	680:727	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
30017190	8	69	theme	marker	1514:1519	arg1	caspase-3					1529:1537	pro-apoptotic marker cleaved caspase-3	1500:1537	pro-apoptotic marker cleaved caspase-3	1500:1537	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	7	70	theme	double	1267:1272	arg1	staining					1293:1300	double immunofluorescence staining	1267:1300	double immunofluorescence staining	1267:1300	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	6	71	theme	diabetic	1020:1027	arg1	retinas					1029:1035	diabetic retinas	1020:1035	diabetic retinas that were more pronounced after metformin treatment of RPE cells	1020:1100	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	2	72	theme	α-lipoic	174:181	arg1	acid					183:186	α-lipoic acid	174:186	α-lipoic acid (α-LA)	174:193	Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice.
30017190	2	72	theme	α-lipoic	174:181	arg1	antioxidant					206:216	a natural antioxidant	196:216	a natural antioxidant	196:216	Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice.
30017190	2	72	theme	α-lipoic	174:181	arg1	α-LA					189:192	α-LA	189:192	α-LA	189:192	Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice.
30017190	8	73	theme	cleaved	1460:1466	arg1	polymerase					1485:1494	cleaved poly(ADP-ribose) polymerase	1460:1494	cleaved poly(ADP-ribose) polymerase	1460:1494	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	7	74	theme	deoxynucleotide	1314:1328	arg1	labelling					1365:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	terminal deoxynucleotide transferase-mediated dUTP nick-end labelling	1305:1373	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	1	75	theme	diabetic	126:133	arg1	retinopathy					135:145	diabetic retinopathy	126:145	diabetic retinopathy	126:145	Oxidative stress plays an important role in the development of diabetic retinopathy.
30017190	3	76	theme	control	299:305	arg1	mice					307:310	control mice	299:310	control mice	299:310	The α-LA was orally administered to control mice or mice with streptozotocin-induced diabetes.
30017190	8	77	theme	caspase-3	1529:1537	arg1	levels					1450:1455	the levels	1446:1455	the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3	1446:1537	Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas.
30017190	9	78	theme	diabetic	1671:1678	arg1	mice					1680:1683	diabetic mice	1671:1683	diabetic mice	1671:1683	Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.
30017190	7	79	from	labelling	1365:1373	arg1	cells					1412:1416	retinal ganglion cells	1395:1416	retinal ganglion cells	1395:1416	Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells.
30017190	1	80	theme	retinopathy	135:145	arg1	development					111:121	the development	107:121	the development of diabetic retinopathy	107:145	Oxidative stress plays an important role in the development of diabetic retinopathy.
30017190	6	81	theme	β-N-acetylglucosamine	933:953	arg1	OGT					968:970	OGT	968:970	OGT	968:970	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	6	81	theme	β-N-acetylglucosamine	933:953	arg1	transferase					955:965	O-linked β-N-acetylglucosamine transferase	924:965	O-linked β-N-acetylglucosamine transferase (OGT)	924:971	Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells.
30017190	5	82	from	levels	670:675	arg1	retinas					760:766	diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose	745:884	retinas	760:766	Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose.
29040017	4	0	theme	acetyl	800:805	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	0	theme	acetyl	800:805	arg1	carboxylase					811:821	acetyl CoA carboxylase	800:821	acetyl CoA carboxylase	800:821	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	11	1	theme	retinal	1807:1813	arg1	injury					1815:1820	SREBP-1-related retinal injury	1791:1820	SREBP-1-related retinal injury	1791:1820	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	1	2	theme	Korean	198:203	arg1	medicine					205:212	traditional Chinese and Korean medicine	174:212	medicine	205:212	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	11	3	from	TXNIP-	1780:1785	arg1	retinopathy					1834:1844	diabetic retinopathy	1825:1844	diabetic retinopathy	1825:1844	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	10	4	theme	AES	1701:1703	arg1	extract					1705:1711	AES extract	1701:1711	AES extract	1701:1711	Moreover, the ChREBP that colocalized with OGT or the TUNEL signal was significantly decreased in diabetic mice treated with AES extract.
29040017	6	5	theme	coimmunoprecipitation	1122:1142	arg1	analysis					1144:1151	coimmunoprecipitation analysis	1122:1151	coimmunoprecipitation analysis	1122:1151	Interaction between ChREBP and OGT was assessed using coimmunoprecipitation analysis.
29040017	3	6	with	mice	495:498	arg1	diabetes					528:535	streptozotocin-induced diabetes	505:535	streptozotocin-induced diabetes	505:535	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	0	7	theme	Transferase	51:61	arg1	Expression					63:72	O-GlcNAc Transferase Expression	42:72	O-GlcNAc Transferase Expression	42:72	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	4	8	theme	carbohydrate-responsive	617:639	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	8	theme	carbohydrate-responsive	617:639	arg1	ChREBP					666:671	ChREBP	666:671	ChREBP	666:671	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	8	theme	carbohydrate-responsive	617:639	arg1	protein					657:663	carbohydrate-responsive element-binding protein	617:663	carbohydrate-responsive element-binding protein (ChREBP)	617:672	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	3	9	theme	streptozotocin-induced	505:526	arg1	diabetes					528:535	streptozotocin-induced diabetes	505:535	streptozotocin-induced diabetes	505:535	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	0	10	theme	Diabetic	100:107	arg1	Mice					109:112	Diabetic Mice	100:112	Diabetic Mice	100:112	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	0	11	from	Expression	63:72	arg1	Mice					109:112	Diabetic Mice	100:112	Diabetic Mice	100:112	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	5	12	theme	OGT	989:991	arg1	Colocalization					864:877	Colocalization	864:877	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP	864:1009	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	9	13	theme	Coimmunoprecipitation	1419:1439	arg1	analysis					1441:1448	Coimmunoprecipitation analysis	1419:1448	Coimmunoprecipitation analysis	1419:1448	Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas.
29040017	0	14	from	Death	91:95	arg1	Mice					109:112	Diabetic Mice	100:112	Diabetic Mice	100:112	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	7	15	theme	diabetic	1282:1289	arg1	retinas					1291:1297	the diabetic retinas	1278:1297	the diabetic retinas	1278:1297	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	4	16	theme	regulatory	682:691	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	16	theme	regulatory	682:691	arg1	SREBP					718:722	SREBP	718:722	SREBP	718:722	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	16	theme	regulatory	682:691	arg1	protein					709:715	sterol regulatory element-binding protein (SREBP)-1	675:725	sterol regulatory element-binding protein (SREBP)-1	675:725	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	1	17	theme	Aralia	115:120	arg1	Miq					129:131	Miq	129:131	Miq	129:131	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	1	17	theme	Aralia	115:120	arg1	elata					122:126	Aralia elata	115:126	Aralia elata (Miq) Seem (AES)	115:143	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	1	17	theme	Aralia	115:120	arg1	plant					160:164	a medicinal plant	148:164	a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes	148:270	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	8	18	theme	diabetic	1401:1408	arg1	retinas					1410:1416	the diabetic retinas	1397:1416	the diabetic retinas	1397:1416	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	0	19	theme	O-GlcNAc	42:49	arg1	Transferase					51:61	O-GlcNAc Transferase	42:61	O-GlcNAc Transferase Expression	42:72	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	9	20	theme	AES	1465:1467	arg1	extract					1469:1475	AES extract	1465:1475	AES extract	1465:1475	Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas.
29040017	2	21	from	injury	384:389	arg1	mice					403:406	diabetic mice	394:406	diabetic mice	394:406	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	8	22	from	ChREBP	1377:1382	arg1	retinas					1410:1416	the diabetic retinas	1397:1416	the diabetic retinas	1397:1416	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	11	23	from	ChREBP-	1771:1777	arg1	retinopathy					1834:1844	diabetic retinopathy	1825:1844	diabetic retinopathy	1825:1844	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	5	24	theme	terminal	882:889	arg1	TUNEL					954:958	TUNEL	954:958	TUNEL	954:958	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	5	24	theme	terminal	882:889	arg1	labeling					944:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling	882:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	0	25	theme	Retinal	78:84	arg1	Death					91:95	Retinal Cell Death	78:95	Retinal Cell Death	78:95	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	5	26	theme	transferase-mediated	907:926	arg1	TUNEL					954:958	TUNEL	954:958	TUNEL	954:958	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	5	26	theme	transferase-mediated	907:926	arg1	labeling					944:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling	882:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	4	27	theme	thioredoxin-interacting	728:750	arg1	TXNIP					761:765	TXNIP	761:765	TXNIP	761:765	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	27	theme	thioredoxin-interacting	728:750	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	27	theme	thioredoxin-interacting	728:750	arg1	protein					752:758	thioredoxin-interacting protein	728:758	thioredoxin-interacting protein (TXNIP)	728:766	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	27	theme	thioredoxin-interacting	728:750	arg1	ACC					824:826	ACC	824:826	ACC	824:826	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	2	28	theme	extract	339:345	arg1	effect					325:330	the neuroprotective effect	305:330	the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice	305:406	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	5	29	theme	immunofluorescence	1039:1056	arg1	analysis					1058:1065	double immunofluorescence analysis	1032:1065	double immunofluorescence analysis	1032:1065	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	5	30	theme	nicked-end	933:942	arg1	TUNEL					954:958	TUNEL	954:958	TUNEL	954:958	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	5	30	theme	nicked-end	933:942	arg1	labeling					944:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling	882:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	7	31	theme	ACC	1271:1273	arg1	levels					1223:1228	levels	1223:1228	levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC	1223:1273	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	8	32	from	TXNIP	1388:1392	arg1	retinas					1410:1416	the diabetic retinas	1397:1416	the diabetic retinas	1397:1416	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	8	33	theme	AES	1300:1302	arg1	extract					1304:1310	AES extract	1300:1310	AES extract	1300:1310	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	11	34	theme	diabetic	1825:1832	arg1	retinopathy					1834:1844	diabetic retinopathy	1825:1844	diabetic retinopathy	1825:1844	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	0	35	theme	Aralia	0:5	arg1	Miq					14:16	Miq	14:16	Miq	14:16	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	0	35	theme	Aralia	0:5	arg1	elata					7:11	Aralia elata	0:11	Aralia elata (Miq)	0:17	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	1	36	dep	elata	122:126	arg1	Seem					134:137	Seem	134:137	Seem (AES)	134:143	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	9	37	theme	cell	1544:1547	arg1	death					1549:1553	ganglion cell death	1535:1553	ganglion cell death in diabetic retinas	1535:1573	Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas.
29040017	2	38	theme	retinal	376:382	arg1	injury					384:389	high glucose-induced retinal injury	355:389	high glucose-induced retinal injury in diabetic mice	355:406	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	9	39	theme	ganglion	1535:1542	arg1	death					1549:1553	ganglion cell death	1535:1553	ganglion cell death in diabetic retinas	1535:1573	Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas.
29040017	4	40	theme	fatty	769:773	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	40	theme	fatty	769:773	arg1	FAS					790:792	FAS	790:792	FAS	790:792	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	40	theme	fatty	769:773	arg1	synthase					780:787	fatty acid synthase	769:787	fatty acid synthase (FAS)	769:793	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	2	41	theme	high	355:358	arg1	injury					384:389	high glucose-induced retinal injury	355:389	high glucose-induced retinal injury in diabetic mice	355:406	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	1	42	theme	diseases	243:250	arg1	treatment					222:230	the treatment	218:230	the treatment of several diseases, including diabetes	218:270	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	4	43	link	O-linked	556:563	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	43	link	O-linked	556:563	arg1	protein					657:663	carbohydrate-responsive element-binding protein	617:663	carbohydrate-responsive element-binding protein (ChREBP)	617:672	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	43	link	O-linked	556:563	arg1	protein					709:715	sterol regulatory element-binding protein (SREBP)-1	675:725	sterol regulatory element-binding protein (SREBP)-1	675:725	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	43	link	O-linked	556:563	arg1	OGT					611:613	OGT	611:613	OGT	611:613	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	43	link	O-linked	556:563	arg1	synthase					780:787	fatty acid synthase	769:787	fatty acid synthase (FAS)	769:793	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	43	link	O-linked	556:563	arg1	protein					752:758	thioredoxin-interacting protein	728:758	thioredoxin-interacting protein (TXNIP)	728:766	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	43	link	O-linked	556:563	arg1	carboxylase					811:821	acetyl CoA carboxylase	800:821	acetyl CoA carboxylase	800:821	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	5	44	theme	ganglion	970:977	arg1	cells					979:983	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	1	45	dep	Seem	134:137	arg1	AES					140:142	AES	140:142	AES	140:142	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	3	46	with	mice	487:490	arg1	diabetes					528:535	streptozotocin-induced diabetes	505:535	streptozotocin-induced diabetes	505:535	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	9	47	theme	diabetic	1558:1565	arg1	retinas					1567:1573	diabetic retinas	1558:1573	diabetic retinas	1558:1573	Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas.
29040017	2	48	theme	neuroprotective	309:323	arg1	effect					325:330	the neuroprotective effect	305:330	the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice	305:406	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	1	49	theme	traditional	174:184	arg1	Chinese					186:192	traditional Chinese and Korean medicine	174:212	Chinese	186:192	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	4	50	theme	β-N-acetylglucosamine	565:585	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	50	theme	β-N-acetylglucosamine	565:585	arg1	protein					657:663	carbohydrate-responsive element-binding protein	617:663	carbohydrate-responsive element-binding protein (ChREBP)	617:672	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	50	theme	β-N-acetylglucosamine	565:585	arg1	protein					709:715	sterol regulatory element-binding protein (SREBP)-1	675:725	sterol regulatory element-binding protein (SREBP)-1	675:725	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	50	theme	β-N-acetylglucosamine	565:585	arg1	OGT					611:613	OGT	611:613	OGT	611:613	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	50	theme	β-N-acetylglucosamine	565:585	arg1	synthase					780:787	fatty acid synthase	769:787	fatty acid synthase (FAS)	769:793	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	50	theme	β-N-acetylglucosamine	565:585	arg1	protein					752:758	thioredoxin-interacting protein	728:758	thioredoxin-interacting protein (TXNIP)	728:766	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	50	theme	β-N-acetylglucosamine	565:585	arg1	carboxylase					811:821	acetyl CoA carboxylase	800:821	acetyl CoA carboxylase	800:821	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	11	51	theme	SREBP-1-related	1791:1805	arg1	injury					1815:1820	SREBP-1-related retinal injury	1791:1820	SREBP-1-related retinal injury	1791:1820	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	11	52	from	OGT-	1765:1768	arg1	retinopathy					1834:1844	diabetic retinopathy	1825:1844	diabetic retinopathy	1825:1844	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	8	53	theme	ganglion	1353:1360	arg1	cells					1362:1366	TUNEL-positive ganglion cells	1338:1366	TUNEL-positive ganglion cells	1338:1366	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	3	54	theme	control	479:485	arg1	mice					487:490	control mice	479:490	control mice	479:490	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	4	55	theme	CoA	807:809	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	55	theme	CoA	807:809	arg1	carboxylase					811:821	acetyl CoA carboxylase	800:821	acetyl CoA carboxylase	800:821	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	56	theme	Protein	538:544	arg1	levels					546:551	Protein levels	538:551	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC)	538:827	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	8	57	from	colocalization	1320:1333	arg1	retinas					1410:1416	the diabetic retinas	1397:1416	the diabetic retinas	1397:1416	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	4	58	theme	acid	775:778	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	58	theme	acid	775:778	arg1	FAS					790:792	FAS	790:792	FAS	790:792	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	58	theme	acid	775:778	arg1	synthase					780:787	fatty acid synthase	769:787	fatty acid synthase (FAS)	769:793	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	8	59	from	OGT	1372:1374	arg1	retinas					1410:1416	the diabetic retinas	1397:1416	the diabetic retinas	1397:1416	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	4	60	theme	O-GlcNAc	588:595	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	60	theme	O-GlcNAc	588:595	arg1	protein					657:663	carbohydrate-responsive element-binding protein	617:663	carbohydrate-responsive element-binding protein (ChREBP)	617:672	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	60	theme	O-GlcNAc	588:595	arg1	protein					709:715	sterol regulatory element-binding protein (SREBP)-1	675:725	sterol regulatory element-binding protein (SREBP)-1	675:725	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	60	theme	O-GlcNAc	588:595	arg1	OGT					611:613	OGT	611:613	OGT	611:613	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	60	theme	O-GlcNAc	588:595	arg1	synthase					780:787	fatty acid synthase	769:787	fatty acid synthase (FAS)	769:793	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	60	theme	O-GlcNAc	588:595	arg1	protein					752:758	thioredoxin-interacting protein	728:758	thioredoxin-interacting protein (TXNIP)	728:766	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	60	theme	O-GlcNAc	588:595	arg1	carboxylase					811:821	acetyl CoA carboxylase	800:821	acetyl CoA carboxylase	800:821	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	11	61	theme	AES	1739:1741	arg1	extract					1743:1749	AES extract	1739:1749	AES extract	1739:1749	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	1	62	theme	medicinal	150:158	arg1	elata					122:126	Aralia elata	115:126	Aralia elata (Miq) Seem (AES)	115:143	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	1	62	theme	medicinal	150:158	arg1	plant					160:164	a medicinal plant	148:164	a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes	148:270	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	4	63	theme	western	846:852	arg1	blotting					854:861	western blotting	846:861	western blotting	846:861	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	64	theme	transferase	598:608	arg1	levels					546:551	Protein levels	538:551	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC)	538:827	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	65	theme	sterol	675:680	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	65	theme	sterol	675:680	arg1	SREBP					718:722	SREBP	718:722	SREBP	718:722	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	65	theme	sterol	675:680	arg1	protein					709:715	sterol regulatory element-binding protein (SREBP)-1	675:725	sterol regulatory element-binding protein (SREBP)-1	675:725	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	7	66	theme	neuronal	1193:1200	arg1	injury					1202:1207	neuronal injury	1193:1207	neuronal injury	1193:1207	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	4	67	theme	element-binding	641:655	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	67	theme	element-binding	641:655	arg1	ChREBP					666:671	ChREBP	666:671	ChREBP	666:671	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	67	theme	element-binding	641:655	arg1	protein					657:663	carbohydrate-responsive element-binding protein	617:663	carbohydrate-responsive element-binding protein (ChREBP)	617:672	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	0	68	theme	Cell	86:89	arg1	Death					91:95	Retinal Cell Death	78:95	Retinal Cell Death	78:95	Aralia elata (Miq) Seem Extract Decreases O-GlcNAc Transferase Expression and Retinal Cell Death in Diabetic Mice.
29040017	5	69	theme	deoxynucleotide	891:905	arg1	TUNEL					954:958	TUNEL	954:958	TUNEL	954:958	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	5	69	theme	deoxynucleotide	891:905	arg1	labeling					944:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling	882:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	11	70	from	injury	1815:1820	arg1	retinopathy					1834:1844	diabetic retinopathy	1825:1844	diabetic retinopathy	1825:1844	These findings show that AES extract can alleviate OGT-, ChREBP-, TXNIP-, or SREBP-1-related retinal injury in diabetic retinopathy.
29040017	7	71	theme	AES	1154:1156	arg1	extract					1158:1164	AES extract	1154:1164	AES extract	1154:1164	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	5	72	theme	double	1032:1037	arg1	analysis					1058:1065	double immunofluorescence analysis	1032:1065	double immunofluorescence analysis	1032:1065	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	5	73	theme	dUTP	928:931	arg1	TUNEL					954:958	TUNEL	954:958	TUNEL	954:958	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	5	73	theme	dUTP	928:931	arg1	labeling					944:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling	882:951	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	2	74	theme	AES	335:337	arg1	extract					339:345	AES extract	335:345	AES extract	335:345	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	7	75	theme	FAS	1262:1264	arg1	levels					1223:1228	levels	1223:1228	levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC	1223:1273	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	2	76	theme	diabetic	394:401	arg1	mice					403:406	diabetic mice	394:406	diabetic mice	394:406	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	4	77	theme	element-binding	693:707	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	77	theme	element-binding	693:707	arg1	SREBP					718:722	SREBP	718:722	SREBP	718:722	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	77	theme	element-binding	693:707	arg1	protein					709:715	sterol regulatory element-binding protein (SREBP)-1	675:725	sterol regulatory element-binding protein (SREBP)-1	675:725	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	7	78	theme	SREBP-1	1253:1259	arg1	levels					1223:1228	levels	1223:1228	levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC	1223:1273	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	2	79	theme	glucose-induced	360:374	arg1	injury					384:389	high glucose-induced retinal injury	355:389	high glucose-induced retinal injury in diabetic mice	355:406	This study aimed to investigate the neuroprotective effect of AES extract against high glucose-induced retinal injury in diabetic mice.
29040017	1	80	theme	several	235:241	arg1	diseases					243:250	several diseases	235:250	several diseases	235:250	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	1	80	theme	several	235:241	arg1	diabetes					263:270	diabetes	263:270	diabetes	263:270	Aralia elata (Miq) Seem (AES) is a medicinal plant used in traditional Chinese and Korean medicine for the treatment of several diseases, including diabetes.
29040017	5	81	theme	-positive	960:968	arg1	cells					979:983	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	9	82	from	death	1549:1553	arg1	retinas					1567:1573	diabetic retinas	1558:1573	diabetic retinas	1558:1573	Coimmunoprecipitation analysis indicated that AES extract reduced interaction between ChREBP and OGT and attenuated ganglion cell death in diabetic retinas.
29040017	7	83	theme	TXNIP	1246:1250	arg1	levels					1223:1228	levels	1223:1228	levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC	1223:1273	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	3	84	theme	AES	409:411	arg1	extract					413:419	AES extract	409:419	AES extract (20 and 100 mg/kg body weight)	409:450	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	3	84	theme	AES	409:411	arg1	weight					444:449	20 and 100 mg/kg body weight	422:449	20 and 100 mg/kg body weight	422:449	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	5	85	theme	cells	979:983	arg1	Colocalization					864:877	Colocalization	864:877	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP	864:1009	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	7	86	theme	ChREBP	1238:1243	arg1	levels					1223:1228	levels	1223:1228	levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC	1223:1273	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	8	87	theme	TUNEL-positive	1338:1351	arg1	cells					1362:1366	TUNEL-positive ganglion cells	1338:1366	TUNEL-positive ganglion cells	1338:1366	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	3	88	theme	body	439:442	arg1	extract					413:419	AES extract	409:419	AES extract (20 and 100 mg/kg body weight)	409:450	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	3	88	theme	body	439:442	arg1	weight					444:449	20 and 100 mg/kg body weight	422:449	20 and 100 mg/kg body weight	422:449	AES extract (20 and 100 mg/kg body weight) was orally administered to control mice or mice with streptozotocin-induced diabetes.
29040017	5	89	theme	labeling	944:951	arg1	cells					979:983	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells	882:983	Colocalization of terminal deoxynucleotide transferase-mediated dUTP nicked-end labeling (TUNEL)-positive ganglion cells and OGT, ChREBP, or TXNIP were monitored using double immunofluorescence analysis.
29040017	7	90	theme	OGT	1233:1235	arg1	levels					1223:1228	levels	1223:1228	levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC	1223:1273	AES extract protected the retinas from neuronal injury and decreased levels of OGT, ChREBP, TXNIP, SREBP-1, FAS, and ACC in the diabetic retinas.
29040017	4	91	theme	O-linked	556:563	arg1	transferase					598:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase	556:608	O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT)	556:614	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	91	theme	O-linked	556:563	arg1	protein					657:663	carbohydrate-responsive element-binding protein	617:663	carbohydrate-responsive element-binding protein (ChREBP)	617:672	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	91	theme	O-linked	556:563	arg1	protein					709:715	sterol regulatory element-binding protein (SREBP)-1	675:725	sterol regulatory element-binding protein (SREBP)-1	675:725	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	91	theme	O-linked	556:563	arg1	OGT					611:613	OGT	611:613	OGT	611:613	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	91	theme	O-linked	556:563	arg1	synthase					780:787	fatty acid synthase	769:787	fatty acid synthase (FAS)	769:793	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	91	theme	O-linked	556:563	arg1	protein					752:758	thioredoxin-interacting protein	728:758	thioredoxin-interacting protein (TXNIP)	728:766	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	4	91	theme	O-linked	556:563	arg1	carboxylase					811:821	acetyl CoA carboxylase	800:821	acetyl CoA carboxylase	800:821	Protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT), carbohydrate-responsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP)-1, thioredoxin-interacting protein (TXNIP), fatty acid synthase (FAS), and acetyl CoA carboxylase (ACC) were analyzed by western blotting.
29040017	8	92	theme	cells	1362:1366	arg1	colocalization					1320:1333	colocalization	1320:1333	colocalization of TUNEL-positive ganglion cells	1320:1366	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	8	92	theme	cells	1362:1366	arg1	TXNIP					1388:1392	TXNIP	1388:1392	TXNIP	1388:1392	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	8	92	theme	cells	1362:1366	arg1	OGT					1372:1374	OGT	1372:1374	OGT	1372:1374	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	8	92	theme	cells	1362:1366	arg1	ChREBP					1377:1382	ChREBP	1377:1382	ChREBP	1377:1382	AES extract reduced colocalization of TUNEL-positive ganglion cells and OGT, ChREBP, or TXNIP in the diabetic retinas.
29040017	10	93	theme	TUNEL	1630:1634	arg1	signal					1636:1641	the TUNEL signal	1626:1641	the TUNEL signal	1626:1641	Moreover, the ChREBP that colocalized with OGT or the TUNEL signal was significantly decreased in diabetic mice treated with AES extract.
29040017	10	94	theme	diabetic	1674:1681	arg1	mice					1683:1686	diabetic mice	1674:1686	diabetic mice treated with AES extract	1674:1711	Moreover, the ChREBP that colocalized with OGT or the TUNEL signal was significantly decreased in diabetic mice treated with AES extract.
31067455	6	0	theme	excess	972:977	arg1	sugar					987:991	excess dietary sugar	972:991	excess dietary sugar	972:991	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	3	1	theme	taste	432:436	arg1	responses					438:446	lower taste responses	426:446	lower taste responses to sweet stimuli	426:463	On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.
31067455	4	2	theme	Excess	505:510	arg1	sugar					520:524	Excess dietary sugar	505:524	Excess dietary sugar	505:524	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	6	3	theme	dietary	979:985	arg1	sugar					987:991	excess dietary sugar	972:991	excess dietary sugar	972:991	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	1	4	with	humans	150:155	arg1	obesity					162:168	obesity	162:168	obesity	162:168	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	4	5	from	transferase	699:709	arg1	neurons					738:744	the sweet-sensing neurons	720:744	the sweet-sensing neurons	720:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	5	6	theme	neurons	829:835	arg1	excitability					793:804	the excitability	789:804	the excitability of the sweet gustatory neurons	789:835	Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity.
31067455	5	7	theme	sweet	813:817	arg1	neurons					829:835	the sweet gustatory neurons	809:835	the sweet gustatory neurons	809:835	Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity.
31067455	4	8	link	O-linked	659:666	arg1	O-GlcNAc					689:696	O-GlcNAc	689:696	O-GlcNAc	689:696	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	4	8	link	O-linked	659:666	arg1	N-Acetylglucosamine					668:686	the sugar sensor O-linked N-Acetylglucosamine	642:686	the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	642:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	5	9	theme	OGT	854:856	arg1	levels					844:849	the levels	840:849	the levels of OGT	840:856	Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity.
31067455	2	10	from	effects	292:298	arg1	sensation					336:344	sweet taste sensation	324:344	sweet taste sensation	324:344	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	2	10	from	effects	292:298	arg1	behavior					358:365	feeding behavior	350:365	feeding behavior in Drosophila melanogaster	350:392	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	5	11	theme	gustatory	819:827	arg1	neurons					829:835	the sweet gustatory neurons	809:835	the sweet gustatory neurons	809:835	Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity.
31067455	1	12	theme	obesity	234:240	arg1	cause					208:212	a cause	206:212	a cause	206:212	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	1	12	theme	obesity	234:240	arg1	consequence					219:229	a consequence	217:229	a consequence of obesity	217:240	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	1	12	theme	obesity	234:240	arg1	change					196:201	this sensory change	183:201	this sensory change	183:201	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	5	13	theme	taste	758:762	arg1	deficits					764:771	taste deficits	758:771	taste deficits	758:771	Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity.
31067455	1	14	dep	find	111:114	arg1	intense					139:145	intense	139:145	intense	139:145	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	2	15	theme	taste	330:334	arg1	sensation					336:344	sweet taste sensation	324:344	sweet taste sensation	324:344	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	4	16	theme	dietary	512:518	arg1	sugar					520:524	Excess dietary sugar	505:524	Excess dietary sugar	505:524	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	6	17	theme	metabolism	1043:1052	arg1	role					1027:1030	the role	1023:1030	the role of glucose metabolism in neural activity and behavior	1023:1084	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	6	18	theme	sweet	947:951	arg1	sensation					959:967	sweet taste sensation	947:967	sweet taste sensation	947:967	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	2	19	theme	sweet	324:328	arg1	sensation					336:344	sweet taste sensation	324:344	sweet taste sensation	324:344	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	0	20	theme	Dietary	5:11	arg1	Taste					34:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.
31067455	3	21	contain	have	421:424	arg2	responses					438:446	lower taste responses	426:446	lower taste responses to sweet stimuli	426:463	On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.
31067455	3	21	contain	have	421:424	arg1	flies					415:419	fruit flies	409:419	fruit flies	409:419	On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.
31067455	4	22	theme	sensor	652:657	arg1	O-GlcNAc					689:696	O-GlcNAc	689:696	O-GlcNAc	689:696	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	4	22	theme	sensor	652:657	arg1	N-Acetylglucosamine					668:686	the sugar sensor O-linked N-Acetylglucosamine	642:686	the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	642:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	0	23	theme	High	0:3	arg1	Taste					34:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.
31067455	4	24	theme	sugar	646:650	arg1	O-GlcNAc					689:696	O-GlcNAc	689:696	O-GlcNAc	689:696	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	4	24	theme	sugar	646:650	arg1	N-Acetylglucosamine					668:686	the sugar sensor O-linked N-Acetylglucosamine	642:686	the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	642:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	2	25	theme	diet	316:319	arg1	effects					292:298	the effects	288:298	the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster	288:392	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	0	26	theme	Reshapes	19:26	arg1	Taste					34:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.
31067455	1	27	theme	Recent	96:101	arg1	studies					103:109	Recent studies	96:109	Recent studies	96:109	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	4	28	theme	dietary	546:552	arg1	sweetness					554:562	dietary sweetness	546:562	dietary sweetness	546:562	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	0	29	theme	Sugar	13:17	arg1	Taste					34:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.
31067455	4	30	theme	transferase	699:709	arg1	action					632:637	the cell-autonomous action	612:637	the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	612:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	1	31	dep	intense	139:145	arg1	tastes					127:132	sugar tastes	121:132	sugar tastes	121:132	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	2	32	theme	feeding	350:356	arg1	behavior					358:365	feeding behavior	350:365	feeding behavior in Drosophila melanogaster	350:392	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	4	33	theme	cell-autonomous	616:630	arg1	action					632:637	the cell-autonomous action	612:637	the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	612:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	6	34	from	role	1027:1030	arg1	behavior					1077:1084	behavior	1077:1084	behavior	1077:1084	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	6	34	from	role	1027:1030	arg1	activity					1064:1071	neural activity	1057:1071	neural activity	1057:1071	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	4	35	theme	sweet-sensing	724:736	arg1	neurons					738:744	the sweet-sensing neurons	720:744	the sweet-sensing neurons	720:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	4	36	theme	taste	578:582	arg1	deficits					584:591	taste deficits	578:591	taste deficits	578:591	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	1	37	theme	sensory	188:194	arg1	cause					208:212	a cause	206:212	a cause	206:212	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	1	37	theme	sensory	188:194	arg1	change					196:201	this sensory change	183:201	this sensory change	183:201	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	0	38	theme	Sweet	28:32	arg1	Taste					34:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste	0:38	High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.
31067455	4	39	from	neurons	738:744	arg1	action					632:637	the cell-autonomous action	612:637	the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	612:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	6	40	theme	neural	1057:1062	arg1	activity					1064:1071	neural activity	1057:1071	neural activity	1057:1071	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	3	41	theme	lower	426:430	arg1	responses					438:446	lower taste responses	426:446	lower taste responses to sweet stimuli	426:463	On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.
31067455	1	42	theme	sugar	121:125	arg1	tastes					127:132	sugar tastes	121:132	sugar tastes	121:132	Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear.
31067455	4	43	theme	N-Acetylglucosamine	668:686	arg1	OGT					712:714	OGT	712:714	OGT	712:714	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	4	43	theme	N-Acetylglucosamine	668:686	arg1	transferase					699:709	the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase	642:709	the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	642:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	6	44	theme	taste	953:957	arg1	sensation					959:967	sweet taste sensation	947:967	sweet taste sensation	947:967	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	5	45	theme	diet-induced	881:892	arg1	obesity					894:900	diet-induced obesity	881:900	diet-induced obesity	881:900	Correcting taste deficits by manipulating the excitability of the sweet gustatory neurons or the levels of OGT protected animals from diet-induced obesity.
31067455	4	46	theme	O-linked	659:666	arg1	O-GlcNAc					689:696	O-GlcNAc	689:696	O-GlcNAc	689:696	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	4	46	theme	O-linked	659:666	arg1	N-Acetylglucosamine					668:686	the sugar sensor O-linked N-Acetylglucosamine	642:686	the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons	642:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	3	47	theme	sweet	451:455	arg1	stimuli					457:463	sweet stimuli	451:463	sweet stimuli	451:463	On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.
31067455	4	48	from	action	632:637	arg1	neurons					738:744	the sweet-sensing neurons	720:744	the sweet-sensing neurons	720:744	Excess dietary sugar, but not obesity or dietary sweetness alone, caused taste deficits and overeating via the cell-autonomous action of the sugar sensor O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in the sweet-sensing neurons.
31067455	3	49	theme	fruit	409:413	arg1	flies					415:419	fruit flies	409:419	fruit flies	409:419	On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.
31067455	2	50	from	sensation	336:344	arg1	melanogaster					381:392	Drosophila melanogaster	370:392	Drosophila melanogaster	370:392	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	2	51	theme	sugar	310:314	arg1	diet					316:319	a high sugar diet	303:319	a high sugar diet	303:319	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	0	52	theme	Feeding	51:57	arg1	Behavior					59:66	Feeding Behavior	51:66	Feeding Behavior	51:66	High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.
31067455	6	53	theme	glucose	1035:1041	arg1	metabolism					1043:1052	glucose metabolism	1035:1052	glucose metabolism	1035:1052	Our work demonstrates that the reshaping of sweet taste sensation by excess dietary sugar drives obesity and highlights the role of glucose metabolism in neural activity and behavior.
31067455	2	54	from	behavior	358:365	arg1	melanogaster					381:392	Drosophila melanogaster	370:392	Drosophila melanogaster	370:392	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
31067455	2	55	theme	high	305:308	arg1	diet					316:319	a high sugar diet	303:319	a high sugar diet	303:319	To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster.
30699359	8	0	theme	modifications	1259:1271	arg1	crosstalk					1227:1235	intricate crosstalk	1217:1235	intricate crosstalk of post-translational modifications of the co-chaperone FNIP1	1217:1297	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	5	1	theme	ATPase	683:688	arg1	activity					690:697	Hsp90 ATPase activity	677:697	Hsp90 ATPase activity	677:697	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	0	2	theme	Chaperone	76:84	arg1	Hsp90					86:90	the Molecular Chaperone Hsp90	62:90	the Molecular Chaperone Hsp90	62:90	Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90.
30699359	5	3	theme	activity	690:697	arg1	activation					711:720	gradual activation	703:720	gradual activation of both kinase and non-kinase clients	703:758	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	5	3	theme	activity	690:697	arg1	inhibition					663:672	incremental inhibition	651:672	incremental inhibition of Hsp90 ATPase activity	651:697	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	4	4	theme	gradual	605:611	arg1	interaction					613:623	its gradual interaction	601:623	its gradual interaction with Hsp90	601:634	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	5	5	theme	gradual	703:709	arg1	activation					711:720	gradual activation	703:720	gradual activation of both kinase and non-kinase clients	703:758	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	4	6	theme	co-chaperone	446:457	arg1	protein					482:488	the co-chaperone folliculin-interacting protein 1	442:490	the co-chaperone folliculin-interacting protein 1 (FNIP1)	442:498	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	6	theme	co-chaperone	446:457	arg1	FNIP1					493:497	FNIP1	493:497	FNIP1	493:497	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	3	7	theme	cellular	376:383	arg1	context					385:391	the cellular context	372:391	the cellular context	372:391	However, it is unclear whether this process occurs abruptly or gradually in the cellular context.
30699359	5	8	theme	incremental	651:661	arg1	inhibition					663:672	incremental inhibition	651:672	incremental inhibition of Hsp90 ATPase activity	651:697	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	7	9	theme	interaction with	1016:1031	arg1	Hsp90					1033:1037	its interaction with Hsp90	1012:1037	its interaction with Hsp90	1012:1037	This process antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 lysine-1119 ubiquitination and proteasomal degradation.
30699359	8	10	theme	co-chaperone	1280:1291	arg1	FNIP1					1293:1297	the co-chaperone FNIP1	1276:1297	the co-chaperone FNIP1	1276:1297	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	4	11	theme	relay	537:541	arg1	phosphorylation					543:557	subsequent relay phosphorylation	526:557	subsequent relay phosphorylation	526:557	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	12	from	phosphorylation	423:437	arg1	serine-939					562:571	serine-939	562:571	serine-939	562:571	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	12	from	phosphorylation	423:437	arg1	948					588:590	948	588:590	948	588:590	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	12	from	phosphorylation	423:437	arg1	serine-938					511:520	priming serine-938	503:520	priming serine-938	503:520	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	12	from	phosphorylation	423:437	arg1	941					574:576	941	574:576	941	574:576	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	12	from	phosphorylation	423:437	arg1	946					579:581	946	579:581	946	579:581	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	12	from	phosphorylation	423:437	arg1	phosphorylation					543:557	subsequent relay phosphorylation	526:557	subsequent relay phosphorylation	526:557	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	8	13	theme	FNIP1	1293:1297	arg1	modifications					1259:1271	post-translational modifications	1240:1271	post-translational modifications of the co-chaperone FNIP1	1240:1297	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	4	14	theme	subsequent	526:535	arg1	phosphorylation					543:557	subsequent relay phosphorylation	526:557	subsequent relay phosphorylation	526:557	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	0	15	theme	Post-translational	0:17	arg1	Regulation					19:28	Post-translational Regulation	0:28	Post-translational Regulation of FNIP1	0:37	Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90.
30699359	7	16	theme	lysine-1119	1072:1082	arg1	ubiquitination					1084:1097	FNIP1 lysine-1119 ubiquitination	1066:1097	FNIP1 lysine-1119 ubiquitination	1066:1097	This process antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 lysine-1119 ubiquitination and proteasomal degradation.
30699359	5	17	theme	Hsp90	677:681	arg1	activity					690:697	Hsp90 ATPase activity	677:697	Hsp90 ATPase activity	677:697	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	4	18	theme	kinase-2	414:421	arg1	phosphorylation					423:437	casein kinase-2 phosphorylation	407:437	casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948	407:590	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	0	19	theme	FNIP1	33:37	arg1	Regulation					19:28	Post-translational Regulation	0:28	Post-translational Regulation of FNIP1	0:37	Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90.
30699359	4	20	theme	casein	407:412	arg1	kinase-2					414:421	casein kinase-2	407:421	casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948	407:590	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	1	21	theme	molecular	97:105	arg1	Hsp90					117:121	The molecular chaperone Hsp90	93:121	The molecular chaperone Hsp90	93:121	The molecular chaperone Hsp90 stabilizes and activates client proteins.
30699359	7	22	theme	proteasomal	1103:1113	arg1	degradation					1115:1125	proteasomal degradation	1103:1125	proteasomal degradation	1103:1125	This process antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 lysine-1119 ubiquitination and proteasomal degradation.
30699359	2	23	dep	Co-chaperones	165:177	arg1	regulate					224:231	regulate	224:231	tightly regulate Hsp90 function and	216:250	Co-chaperones and post-translational modifications tightly regulate Hsp90 function and consequently lead to activation of clients.
30699359	5	24	theme	non-kinase	741:750	arg1	clients					752:758	non-kinase clients	741:758	non-kinase clients	741:758	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	1	25	theme	chaperone	107:115	arg1	Hsp90					117:121	The molecular chaperone Hsp90	93:121	The molecular chaperone Hsp90	93:121	The molecular chaperone Hsp90 stabilizes and activates client proteins.
30699359	8	26	theme	post-translational	1240:1257	arg1	modifications					1259:1271	post-translational modifications	1240:1271	post-translational modifications of the co-chaperone FNIP1	1240:1297	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	6	27	link	O-linked	893:900	arg1	O-GlcNAc					883:890	O-GlcNAc	883:890	O-GlcNAc (O-linked N-acetylglucosamine)	883:921	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	6	27	link	O-linked	893:900	arg1	N-acetylglucosamine					902:920	O-linked N-acetylglucosamine	893:920	O-linked N-acetylglucosamine	893:920	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	5	28	theme	clients	752:758	arg1	activation					711:720	gradual activation	703:720	gradual activation of both kinase and non-kinase clients	703:758	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	5	28	theme	clients	752:758	arg1	inhibition					663:672	incremental inhibition	651:672	incremental inhibition of Hsp90 ATPase activity	651:697	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	8	29	theme	gradual	1167:1173	arg1	activation					1175:1184	gradual activation	1167:1184	gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1	1167:1297	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	4	30	theme	priming	503:509	arg1	serine-938					511:520	priming serine-938	503:520	priming serine-938	503:520	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	8	31	theme	proteins	1200:1207	arg1	activation					1175:1184	gradual activation	1167:1184	gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1	1167:1297	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	6	32	theme	O-linked	893:900	arg1	O-GlcNAc					883:890	O-GlcNAc	883:890	O-GlcNAc (O-linked N-acetylglucosamine)	883:921	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	6	32	theme	O-linked	893:900	arg1	N-acetylglucosamine					902:920	O-linked N-acetylglucosamine	893:920	O-linked N-acetylglucosamine	893:920	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	6	33	theme	priming	930:936	arg1	serine-938					938:947	the priming serine-938	926:947	the priming serine-938	926:947	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	8	34	theme	client	1193:1198	arg1	proteins					1200:1207	the client proteins	1189:1207	the client proteins	1189:1207	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	4	35	theme	protein	482:488	arg1	phosphorylation					423:437	casein kinase-2 phosphorylation	407:437	casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948	407:590	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	6	36	theme	O-GlcNAc	883:890	arg1	addition					871:878	the addition	867:878	the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938	867:947	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	6	37	theme	protein	806:812	arg1	phosphatase					814:824	serine/threonine protein phosphatase 5	789:826	serine/threonine protein phosphatase 5 (PP5)	789:832	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	6	37	theme	protein	806:812	arg1	PP5					829:831	PP5	829:831	PP5	829:831	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	2	38	theme	post-translational	183:200	arg1	modifications					202:214	post-translational modifications	183:214	post-translational modifications	183:214	Co-chaperones and post-translational modifications tightly regulate Hsp90 function and consequently lead to activation of clients.
30699359	7	39	theme	FNIP1	994:998	arg1	phosphorylation					975:989	phosphorylation	975:989	phosphorylation of FNIP1	975:998	This process antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 lysine-1119 ubiquitination and proteasomal degradation.
30699359	8	40	theme	intricate	1217:1225	arg1	crosstalk					1227:1235	intricate crosstalk	1217:1235	intricate crosstalk of post-translational modifications of the co-chaperone FNIP1	1217:1297	These findings provide a mechanism for gradual activation of the client proteins through intricate crosstalk of post-translational modifications of the co-chaperone FNIP1.
30699359	4	41	theme	folliculin-interacting	459:480	arg1	protein					482:488	the co-chaperone folliculin-interacting protein 1	442:490	the co-chaperone folliculin-interacting protein 1 (FNIP1)	442:498	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	4	41	theme	folliculin-interacting	459:480	arg1	FNIP1					493:497	FNIP1	493:497	FNIP1	493:497	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	6	42	theme	serine/threonine	789:804	arg1	phosphatase					814:824	serine/threonine protein phosphatase 5	789:826	serine/threonine protein phosphatase 5 (PP5)	789:832	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	6	42	theme	serine/threonine	789:804	arg1	PP5					829:831	PP5	829:831	PP5	829:831	We further demonstrate that serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1, allowing the addition of O-GlcNAc (O-linked N-acetylglucosamine) to the priming serine-938.
30699359	5	43	theme	kinase	730:735	arg1	activation					711:720	gradual activation	703:720	gradual activation of both kinase and non-kinase clients	703:758	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	5	43	theme	kinase	730:735	arg1	inhibition					663:672	incremental inhibition	651:672	incremental inhibition of Hsp90 ATPase activity	651:697	This leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients.
30699359	2	44	theme	Hsp90	233:237	arg1	function and					239:250	Hsp90 function and	233:250	Hsp90 function and	233:250	Co-chaperones and post-translational modifications tightly regulate Hsp90 function and consequently lead to activation of clients.
30699359	0	45	theme	Molecular	66:74	arg1	Hsp90					86:90	the Molecular Chaperone Hsp90	62:90	the Molecular Chaperone Hsp90	62:90	Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90.
30699359	4	46	with	interaction	613:623	arg1	Hsp90					630:634	Hsp90	630:634	Hsp90	630:634	We show that casein kinase-2 phosphorylation of the co-chaperone folliculin-interacting protein 1 (FNIP1) on priming serine-938 and subsequent relay phosphorylation on serine-939, 941, 946, and 948 promotes its gradual interaction with Hsp90.
30699359	7	47	theme	FNIP1	1066:1070	arg1	ubiquitination					1084:1097	FNIP1 lysine-1119 ubiquitination	1066:1097	FNIP1 lysine-1119 ubiquitination	1066:1097	This process antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 lysine-1119 ubiquitination and proteasomal degradation.
30699359	1	48	theme	client	148:153	arg1	proteins					155:162	client proteins	148:162	client proteins	148:162	The molecular chaperone Hsp90 stabilizes and activates client proteins.
30699359	2	49	theme	clients	287:293	arg1	activation					273:282	activation	273:282	activation of clients	273:293	Co-chaperones and post-translational modifications tightly regulate Hsp90 function and consequently lead to activation of clients.
28369504	7	0	theme	Siglec-8	1180:1187	arg1	ligands					1189:1195	Siglec-8 ligands	1180:1195	Siglec-8 ligands	1180:1195	Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species.
28369504	10	1	theme	distributions	1833:1845	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	1	theme	distributions	1833:1845	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	4	2	contain	have	784:787	arg1	Siglec-E					760:767	Siglec-E	760:767	Siglec-E	760:767	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	2	contain	have	784:787	arg1	counterparts					734:745	their mouse counterparts Siglec-F and Siglec-E (respectively)	722:782	their mouse counterparts Siglec-F and Siglec-E (respectively)	722:782	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	2	contain	have	784:787	arg1	Siglec-8					699:706	Siglec-8	699:706	Siglec-8	699:706	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	2	contain	have	784:787	arg2	specificities					813:825	distinct glycan binding specificities	789:825	distinct glycan binding specificities	789:825	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	2	contain	have	784:787	arg1	Siglec-F					747:754	Siglec-F	747:754	Siglec-F	747:754	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	2	contain	have	784:787	arg1	Siglec-9					709:716	Siglec-9	709:716	Siglec-9	709:716	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	6	3	theme	tracheal	1014:1021	arg1	glands					1034:1039	tracheal submucosal glands	1014:1039	tracheal submucosal glands	1014:1039	Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed.
28369504	4	4	theme	array	666:670	arg1	analyses					672:679	Glycan array analyses	659:679	Glycan array analyses	659:679	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	10	5	theme	molecular	1851:1859	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	9	6	link	O-linked	1663:1670	arg1	sialoglycoproteins					1672:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	1	7	theme	binding	141:147	arg1	proteins					149:156	transmembrane sialoglycan binding proteins	115:156	transmembrane sialoglycan binding proteins	115:156	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	1	7	theme	binding	141:147	arg1	Siglecs					103:109	Siglecs	103:109	Siglecs	103:109	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	8	8	theme	Siglec-9	1504:1511	arg1	ligands					1513:1519	Siglec-9 ligands	1504:1519	Siglec-9 ligands	1504:1519	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	8	9	theme	siglec	1335:1340	arg1	blotting					1342:1349	electrophoretic resolution and siglec blotting	1304:1349	blotting	1342:1349	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	10	10	theme	sialoglycan	1902:1912	arg1	ligands					1914:1920	Siglec-8 and Siglec-9 sialoglycan ligands	1880:1920	Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1880:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	5	11	theme	lung	902:905	arg1	inflammation					907:918	lung inflammation	902:918	lung inflammation	902:918	Since siglecs are involved in lung inflammation, we studied Siglec-8 and Siglec-9 ligands in human lungs and airways.
28369504	8	12	theme	airways	1275:1281	arg1	lung					1287:1290	lung	1287:1290	lung	1287:1290	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	8	12	theme	airways	1275:1281	arg1	Extraction					1255:1264	Extraction	1255:1264	Extraction of human airways	1255:1281	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	6	13	theme	Siglec-8	990:997	arg1	ligands					999:1005	Siglec-8 ligands	990:1005	Siglec-8 ligands	990:1005	Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed.
28369504	5	14	theme	human	965:969	arg1	lungs					971:975	human lungs	965:975	human lungs	965:975	Since siglecs are involved in lung inflammation, we studied Siglec-8 and Siglec-9 ligands in human lungs and airways.
28369504	2	15	theme	anti-inflammatory	502:518	arg1	release					529:535	anti-inflammatory mediator release	502:535	anti-inflammatory mediator release	502:535	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	8	16	theme	airway	1545:1550	arg1	tissues					1561:1567	all airway and lung tissues	1541:1567	tissues	1561:1567	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	0	17	theme	ligand	66:71	arg1	distributions					73:85	endogenous airway ligand distributions	48:85	endogenous airway ligand distributions	48:85	Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties.
28369504	10	18	from	characteristics	1861:1875	arg1	lungs					1943:1947	lungs	1943:1947	lungs	1943:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	18	from	characteristics	1861:1875	arg1	airways					1931:1937	human airways	1925:1937	human airways	1925:1937	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	6	19	dep	glands	1034:1039	arg1	whereas					1104:1110	whereas	1104:1110	whereas	1104:1110	Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed.
28369504	8	20	theme	human	1392:1396	arg1	trachea					1398:1404	human trachea	1392:1404	human trachea	1392:1404	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	3	21	from	ligands	561:567	arg1	tissues					572:578	tissues	572:578	tissues	572:578	Endogenous sialoglycan ligands in tissues, mostly uncharacterized, engage siglecs on leukocytes to inhibit inflammation.
28369504	4	22	theme	binding	805:811	arg1	specificities					813:825	distinct glycan binding specificities	789:825	distinct glycan binding specificities	789:825	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	7	23	contain	have	1175:1178	arg2	ligands					1189:1195	Siglec-8 ligands	1180:1195	Siglec-8 ligands	1180:1195	Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species.
28369504	7	23	contain	have	1175:1178	arg1	airways					1160:1166	Mouse airways	1154:1166	Mouse airways	1154:1166	Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species.
28369504	2	24	theme	release	529:535	arg1	enhancement					487:497	enhancement	487:497	enhancement of anti-inflammatory mediator release	487:535	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	8	25	theme	tracheal	1419:1426	arg1	cells					1434:1438	cultured tracheal gland cells	1410:1438	cultured tracheal gland cells	1410:1438	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	10	26	from	ligands	1914:1920	arg1	lungs					1943:1947	lungs	1943:1947	lungs	1943:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	26	from	ligands	1914:1920	arg1	airways					1931:1937	human airways	1925:1937	human airways	1925:1937	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	27	theme	glycan	1723:1728	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	0	28	theme	Siglec-8	0:7	arg1	specificities					30:42	Siglec-8 and Siglec-9 binding specificities	0:42	Siglec-8 and Siglec-9 binding specificities	0:42	Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties.
28369504	6	29	theme	Siglec-9	1112:1119	arg1	ligands					1121:1127	Siglec-9 ligands	1112:1127	Siglec-9 ligands	1112:1127	Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed.
28369504	4	30	theme	distinct	789:796	arg1	specificities					813:825	distinct glycan binding specificities	789:825	distinct glycan binding specificities	789:825	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	3	31	from	siglecs	612:618	arg1	leukocytes					623:632	leukocytes	623:632	leukocytes	623:632	Endogenous sialoglycan ligands in tissues, mostly uncharacterized, engage siglecs on leukocytes to inhibit inflammation.
28369504	2	32	theme	immune	423:428	arg1	death					435:439	immune cell death	423:439	immune cell death	423:439	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	0	33	theme	Siglec-9	13:20	arg1	specificities					30:42	Siglec-8 and Siglec-9 binding specificities	0:42	Siglec-8 and Siglec-9 binding specificities	0:42	Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties.
28369504	10	34	theme	tissue	1826:1831	arg1	distributions					1833:1845	the tissue distributions	1822:1845	the tissue distributions	1822:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	9	35	theme	high	1641:1644	arg1	sialoglycoproteins					1672:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	2	36	theme	release	472:478	arg1	inhibition					442:451	inhibition	442:451	inhibition of immune mediator release	442:478	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	7	37	theme	Siglec-9	1206:1213	arg1	ligands					1215:1221	Siglec-9 ligands	1206:1221	Siglec-9 ligands	1206:1221	Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species.
28369504	9	38	theme	weight	1656:1661	arg1	sialoglycoproteins					1672:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	6	39	theme	connective	1084:1093	arg1	tissues					1095:1101	connective tissues	1084:1101	connective tissues	1084:1101	Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed.
28369504	2	40	theme	immune	456:461	arg1	release					472:478	immune mediator release	456:478	immune mediator release	456:478	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	8	41	theme	cultured	1463:1470	arg1	cells					1490:1494	cultured airway epithelial cells	1463:1494	cultured airway epithelial cells	1463:1494	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	0	42	theme	endogenous	48:57	arg1	distributions					73:85	endogenous airway ligand distributions	48:85	endogenous airway ligand distributions	48:85	Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties.
28369504	8	43	theme	epithelial	1479:1488	arg1	cells					1490:1494	cultured airway epithelial cells	1463:1494	cultured airway epithelial cells	1463:1494	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	10	44	theme	mouse	1776:1780	arg1	counterparts					1782:1793	their mouse counterparts Siglec-F and Siglec-E	1770:1815	their mouse counterparts Siglec-F and Siglec-E	1770:1815	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	44	theme	mouse	1776:1780	arg1	Siglec-E					1808:1815	Siglec-E	1808:1815	Siglec-E	1808:1815	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	44	theme	mouse	1776:1780	arg1	Siglec-F					1795:1802	Siglec-F	1795:1802	Siglec-F	1795:1802	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	1	45	theme	cell	250:253	arg1	ligation					263:270	cell surface ligation	250:270	cell surface ligation	250:270	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	10	46	from	lungs	1943:1947	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	46	from	lungs	1943:1947	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	8	47	theme	lung	1556:1559	arg1	tissues					1561:1567	all airway and lung tissues	1541:1567	tissues	1561:1567	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	1	48	theme	immune	277:282	arg1	suppression					284:294	immune suppression	277:294	immune suppression	277:294	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	3	49	theme	uncharacterized	588:602	arg1	ligands					561:567	Endogenous sialoglycan ligands	538:567	Endogenous sialoglycan ligands	538:567	Endogenous sialoglycan ligands in tissues, mostly uncharacterized, engage siglecs on leukocytes to inhibit inflammation.
28369504	9	50	theme	Siglec-8	1587:1594	arg1	ligands					1609:1615	Siglec-8 and Siglec-9 ligands	1587:1615	Siglec-8 and Siglec-9 ligands in airways	1587:1626	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	7	51	theme	Mouse	1154:1158	arg1	airways					1160:1166	Mouse airways	1154:1166	Mouse airways	1154:1166	Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species.
28369504	3	52	theme	sialoglycan	549:559	arg1	ligands					561:567	Endogenous sialoglycan ligands	538:567	Endogenous sialoglycan ligands	538:567	Endogenous sialoglycan ligands in tissues, mostly uncharacterized, engage siglecs on leukocytes to inhibit inflammation.
28369504	2	53	from	Siglec-9	362:369	arg1	eosinophils					320:330	eosinophils	320:330	eosinophils	320:330	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	53	from	Siglec-9	362:369	arg1	T-cells					406:412	some T-cells	401:412	some T-cells	401:412	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	53	from	Siglec-9	362:369	arg1	neutrophils					374:384	neutrophils	374:384	neutrophils	374:384	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	53	from	Siglec-9	362:369	arg1	cells					338:342	mast cells	333:342	mast cells	333:342	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	53	from	Siglec-9	362:369	arg1	basophils					348:356	basophils	348:356	basophils	348:356	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	53	from	Siglec-9	362:369	arg1	monocytes					387:395	monocytes	387:395	monocytes	387:395	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	10	54	theme	Siglec-8	1880:1887	arg1	ligands					1914:1920	Siglec-8 and Siglec-9 sialoglycan ligands	1880:1920	Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1880:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	1	55	theme	leukocyte	190:198	arg1	subsets					200:206	leukocyte subsets	190:206	leukocyte subsets	190:206	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	6	56	theme	submucosal	1023:1032	arg1	glands					1034:1039	tracheal submucosal glands	1014:1039	tracheal submucosal glands	1014:1039	Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed.
28369504	7	57	dep	have	1175:1178	arg1	whereas					1198:1204	whereas	1198:1204	whereas	1198:1204	Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species.
28369504	8	58	theme	electrophoretic	1304:1318	arg1	resolution					1320:1329	electrophoretic resolution and siglec blotting	1304:1349	resolution	1320:1329	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	10	59	theme	ligands	1914:1920	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	59	theme	ligands	1914:1920	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	1	60	theme	inhibitory	217:226	arg1	motifs					228:233	inhibitory motifs	217:233	inhibitory motifs that translate cell surface ligation into immune suppression	217:294	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	10	61	theme	Siglec-9	1893:1900	arg1	ligands					1914:1920	Siglec-8 and Siglec-9 sialoglycan ligands	1880:1920	Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1880:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	1	62	theme	sialoglycan	129:139	arg1	proteins					149:156	transmembrane sialoglycan binding proteins	115:156	transmembrane sialoglycan binding proteins	115:156	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	1	62	theme	sialoglycan	129:139	arg1	Siglecs					103:109	Siglecs	103:109	Siglecs	103:109	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	8	63	theme	human	1269:1273	arg1	airways					1275:1281	human airways	1269:1281	human airways	1269:1281	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	4	64	dep	counterparts	734:745	arg1	counterparts					734:745	their mouse counterparts Siglec-F and Siglec-E (respectively)	722:782	their mouse counterparts Siglec-F and Siglec-E (respectively)	722:782	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	64	dep	counterparts	734:745	arg1	Siglec-E					760:767	Siglec-E	760:767	Siglec-E	760:767	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	64	dep	counterparts	734:745	arg1	Siglec-F					747:754	Siglec-F	747:754	Siglec-F	747:754	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	8	65	theme	Siglec-8	1360:1367	arg1	ligands					1369:1375	Siglec-8 ligands	1360:1375	Siglec-8 ligands	1360:1375	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	10	66	theme	human	1925:1929	arg1	airways					1931:1937	human airways	1925:1937	human airways	1925:1937	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	5	67	theme	Siglec-8	932:939	arg1	ligands					954:960	Siglec-8 and Siglec-9 ligands	932:960	Siglec-8 and Siglec-9 ligands	932:960	Since siglecs are involved in lung inflammation, we studied Siglec-8 and Siglec-9 ligands in human lungs and airways.
28369504	6	68	theme	airway	1063:1068	arg1	epithelium					1070:1079	airway epithelium	1063:1079	airway epithelium	1063:1079	Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed.
28369504	5	69	theme	Siglec-9	945:952	arg1	ligands					954:960	Siglec-8 and Siglec-9 ligands	932:960	Siglec-8 and Siglec-9 ligands	932:960	Since siglecs are involved in lung inflammation, we studied Siglec-8 and Siglec-9 ligands in human lungs and airways.
28369504	2	70	from	Siglec-8	308:315	arg1	eosinophils					320:330	eosinophils	320:330	eosinophils	320:330	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	70	from	Siglec-8	308:315	arg1	T-cells					406:412	some T-cells	401:412	some T-cells	401:412	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	70	from	Siglec-8	308:315	arg1	neutrophils					374:384	neutrophils	374:384	neutrophils	374:384	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	70	from	Siglec-8	308:315	arg1	cells					338:342	mast cells	333:342	mast cells	333:342	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	70	from	Siglec-8	308:315	arg1	basophils					348:356	basophils	348:356	basophils	348:356	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	2	70	from	Siglec-8	308:315	arg1	monocytes					387:395	monocytes	387:395	monocytes	387:395	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	4	71	theme	mouse	728:732	arg1	counterparts					734:745	their mouse counterparts Siglec-F and Siglec-E (respectively)	722:782	their mouse counterparts Siglec-F and Siglec-E (respectively)	722:782	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	71	theme	mouse	728:732	arg1	Siglec-E					760:767	Siglec-E	760:767	Siglec-E	760:767	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	4	71	theme	mouse	728:732	arg1	Siglec-F					747:754	Siglec-F	747:754	Siglec-F	747:754	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	7	72	theme	species	1246:1252	arg1	airways					1230:1236	airways	1230:1236	airways of both species	1230:1252	Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species.
28369504	9	73	theme	Siglec-9	1600:1607	arg1	ligands					1609:1615	Siglec-8 and Siglec-9 ligands	1587:1615	Siglec-8 and Siglec-9 ligands in airways	1587:1626	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	9	74	from	ligands	1609:1615	arg1	airways					1620:1626	airways	1620:1626	airways	1620:1626	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	4	75	theme	glycan	798:803	arg1	specificities					813:825	distinct glycan binding specificities	789:825	distinct glycan binding specificities	789:825	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	8	76	theme	trachea	1398:1404	arg1	extracts					1380:1387	extracts	1380:1387	extracts of human trachea	1380:1404	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	4	77	theme	Glycan	659:664	arg1	analyses					672:679	Glycan array analyses	659:679	Glycan array analyses	659:679	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	2	78	theme	mediator	520:527	arg1	release					529:535	anti-inflammatory mediator release	502:535	anti-inflammatory mediator release	502:535	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	8	79	theme	cultured	1410:1417	arg1	cells					1434:1438	cultured tracheal gland cells	1410:1438	cultured tracheal gland cells	1410:1438	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	8	80	theme	gland	1428:1432	arg1	cells					1434:1438	cultured tracheal gland cells	1410:1438	cultured tracheal gland cells	1410:1438	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	10	81	theme	differential	1710:1721	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	0	82	theme	binding	22:28	arg1	specificities					30:42	Siglec-8 and Siglec-9 binding specificities	0:42	Siglec-8 and Siglec-9 binding specificities	0:42	Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties.
28369504	2	83	theme	cell	430:433	arg1	death					435:439	immune cell death	423:439	immune cell death	423:439	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	10	84	dep	counterparts	1782:1793	arg1	counterparts					1782:1793	their mouse counterparts Siglec-F and Siglec-E	1770:1815	their mouse counterparts Siglec-F and Siglec-E	1770:1815	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	84	dep	counterparts	1782:1793	arg1	Siglec-E					1808:1815	Siglec-E	1808:1815	Siglec-E	1808:1815	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	84	dep	counterparts	1782:1793	arg1	Siglec-F					1795:1802	Siglec-F	1795:1802	Siglec-F	1795:1802	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	85	theme	Siglec-9	1757:1764	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	85	theme	Siglec-9	1757:1764	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	9	86	theme	molecular	1646:1654	arg1	sialoglycoproteins					1672:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	10	87	from	airways	1931:1937	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	87	from	airways	1931:1937	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	2	88	theme	mediator	463:470	arg1	release					472:478	immune mediator release	456:478	immune mediator release	456:478	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	4	89	theme	restricted	860:869	arg1	Siglec-8					833:840	Siglec-8	833:840	Siglec-8 more structurally restricted	833:869	Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted.
28369504	10	90	theme	Siglec-8	1747:1754	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	90	theme	Siglec-8	1747:1754	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	0	91	theme	airway	59:64	arg1	distributions					73:85	endogenous airway ligand distributions	48:85	endogenous airway ligand distributions	48:85	Siglec-8 and Siglec-9 binding specificities and endogenous airway ligand distributions and properties.
28369504	9	92	theme	O-linked	1663:1670	arg1	sialoglycoproteins					1672:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	10	93	theme	counterparts	1782:1793	arg1	specificities					1730:1742	differential glycan specificities	1710:1742	differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions	1710:1845	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	93	theme	counterparts	1782:1793	arg1	characteristics					1861:1875	molecular characteristics	1851:1875	molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs	1851:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	1	94	theme	transmembrane	115:127	arg1	proteins					149:156	transmembrane sialoglycan binding proteins	115:156	transmembrane sialoglycan binding proteins	115:156	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	1	94	theme	transmembrane	115:127	arg1	Siglecs					103:109	Siglecs	103:109	Siglecs	103:109	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	10	95	from	specificities	1730:1742	arg1	lungs					1943:1947	lungs	1943:1947	lungs	1943:1947	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	10	95	from	specificities	1730:1742	arg1	airways					1931:1937	human airways	1925:1937	human airways	1925:1937	These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
28369504	1	96	contain	have	212:215	arg2	motifs					228:233	inhibitory motifs	217:233	inhibitory motifs that translate cell surface ligation into immune suppression	217:294	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	1	96	contain	have	212:215	arg1	proteins					149:156	transmembrane sialoglycan binding proteins	115:156	transmembrane sialoglycan binding proteins	115:156	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	1	96	contain	have	212:215	arg1	most					159:162	most	159:162	most	159:162	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	1	96	contain	have	212:215	arg1	Siglecs					103:109	Siglecs	103:109	Siglecs	103:109	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28369504	8	97	theme	airway	1472:1477	arg1	cells					1490:1494	cultured airway epithelial cells	1463:1494	cultured airway epithelial cells	1463:1494	Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested.
28369504	2	98	theme	mast	333:336	arg1	cells					338:342	mast cells	333:342	mast cells	333:342	In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release.
28369504	9	99	gly	sialoglycoproteins	1672:1689	arg1	sialoglycoproteins					1672:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	high molecular weight O-linked sialoglycoproteins	1641:1689	Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins.
28369504	3	100	theme	Endogenous	538:547	arg1	ligands					561:567	Endogenous sialoglycan ligands	538:567	Endogenous sialoglycan ligands	538:567	Endogenous sialoglycan ligands in tissues, mostly uncharacterized, engage siglecs on leukocytes to inhibit inflammation.
28369504	1	101	theme	surface	255:261	arg1	ligation					263:270	cell surface ligation	250:270	cell surface ligation	250:270	Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression.
28534487	1	0	theme	protein	291:297	arg1	VP1					299:301	capsid protein VP1	284:301	capsid protein VP1	284:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	6	1	theme	integrin	1004:1011	arg1	sugar					991:995	an N-linked sugar	979:995	an N-linked sugar of the integrin	979:1011	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	2	2	theme	heparin	434:440	arg1	HS					452:453	HS	452:453	HS	452:453	Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections.
28534487	2	2	theme	heparin	434:440	arg1	sulphate					442:449	heparin sulphate	434:449	heparin sulphate (HS)	434:454	Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections.
28534487	1	3	theme	VP1	299:301	arg1	loop					276:279	the exposed, antigenic, GH loop	249:279	the exposed, antigenic, GH loop of capsid protein VP1	249:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	1	4	dep	exposed	253:259	arg1	antigenic					262:270	antigenic	262:270	antigenic	262:270	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	4	5	theme	FMDV	708:711	arg1	strains					713:719	αvβ6 and two tissue culture adapted FMDV strains	672:719	strains	713:719	Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy.
28534487	5	6	theme	extended	875:882	arg1	loop					887:890	an extended GH loop	872:890	an extended GH loop	872:890	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	3	7	theme	HS	505:506	arg1	interaction					508:518	HS interaction	505:518	HS interaction	505:518	HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding.
28534487	4	8	theme	adapted	700:706	arg1	strains					713:719	αvβ6 and two tissue culture adapted FMDV strains	672:719	strains	713:719	Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy.
28534487	4	9	theme	αvβ6	672:675	arg1	strains					713:719	αvβ6 and two tissue culture adapted FMDV strains	672:719	strains	713:719	Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy.
28534487	5	10	theme	open	797:800	arg1	form					802:805	the fully open form	787:805	the fully open form	787:805	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	4	11	theme	two	681:683	arg1	strains					713:719	αvβ6 and two tissue culture adapted FMDV strains	672:719	strains	713:719	Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy.
28534487	6	12	theme	functional	1081:1090	arg1	role					1092:1095	a functional role	1079:1095	a functional role	1079:1095	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	6	13	theme	N-linked	982:989	arg1	sugar					991:995	an N-linked sugar	979:995	an N-linked sugar of the integrin	979:1011	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	1	14	theme	integrin	152:159	arg1	receptor					161:168	an integrin receptor	149:168	an integrin receptor	149:168	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	1	15	theme	Foot-and-mouth	76:89	arg1	virus					99:103	Foot-and-mouth disease virus	76:103	Foot-and-mouth disease virus (FMDV)	76:110	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	1	15	theme	Foot-and-mouth	76:89	arg1	FMDV					106:109	FMDV	106:109	FMDV	106:109	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	3	16	from	site	555:558	arg1	serotypes					567:575	two serotypes	563:575	two serotypes suggesting a propensity for sulfated-sugar binding	563:626	HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding.
28534487	2	17	theme	acquired	392:399	arg1	mutations					407:415	acquired basic mutations	392:415	acquired basic mutations interacting with heparin sulphate (HS)	392:454	Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections.
28534487	1	18	theme	disease	91:97	arg1	virus					99:103	Foot-and-mouth disease virus	76:103	Foot-and-mouth disease virus (FMDV)	76:110	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	1	18	theme	disease	91:97	arg1	FMDV					106:109	FMDV	106:109	FMDV	106:109	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	2	19	theme	tissue	332:337	arg1	culture					339:345	tissue culture	332:345	tissue culture adapted virus in the absence of integrin	332:386	Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections.
28534487	5	20	theme	preferred	757:765	arg1	mode					767:770	the preferred mode	753:770	the preferred mode of engagement	753:784	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	2	21	theme	integrin	379:386	arg1	absence					368:374	the absence	364:374	the absence of integrin	364:386	Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections.
28534487	1	22	theme	exposed	253:259	arg1	loop					276:279	the exposed, antigenic, GH loop	249:279	the exposed, antigenic, GH loop of capsid protein VP1	249:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	2	23	theme	natural	485:491	arg1	infections					493:502	natural infections	485:502	natural infections	485:502	Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections.
28534487	6	24	theme	binding	1054:1060	arg1	site					1062:1065	the previously identified HS binding site	1025:1065	the previously identified HS binding site	1025:1065	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	4	25	theme	culture	692:698	arg1	strains					713:719	αvβ6 and two tissue culture adapted FMDV strains	672:719	strains	713:719	Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy.
28534487	5	26	theme	GH	884:885	arg1	loop					887:890	an extended GH loop	872:890	an extended GH loop	872:890	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	0	27	theme	engagement	9:18	arg1	Rules					0:4	Rules	0:4	Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus	0:73	Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus.
28534487	6	28	attach	attaches	1013:1020	arg2	sugar					991:995	an N-linked sugar	979:995	an N-linked sugar of the integrin	979:1011	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	6	28	attach	attaches	1013:1020	arg1	site					1062:1065	the previously identified HS binding site	1025:1065	the previously identified HS binding site	1025:1065	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	4	29	theme	tissue	685:690	arg1	strains					713:719	αvβ6 and two tissue culture adapted FMDV strains	672:719	strains	713:719	Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy.
28534487	6	30	theme	identified	1040:1049	arg1	site					1062:1065	the previously identified HS binding site	1025:1065	the previously identified HS binding site	1025:1065	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	0	31	theme	αvβ6	28:31	arg1	integrin					33:40	αvβ6 integrin	28:40	αvβ6 integrin	28:40	Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus.
28534487	5	32	with	interactions	896:907	arg1	motif					922:926	the RGD motif	914:926	the RGD motif	914:926	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	5	32	with	interactions	896:907	arg1	residues					956:963	downstream hydrophobic residues	933:963	downstream hydrophobic residues	933:963	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	5	33	theme	downstream	933:942	arg1	residues					956:963	downstream hydrophobic residues	933:963	downstream hydrophobic residues	933:963	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	0	34	theme	foot-and-mouth	46:59	arg1	virus					69:73	foot-and-mouth disease virus	46:73	foot-and-mouth disease virus	46:73	Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus.
28534487	1	35	theme	GH	273:274	arg1	loop					276:279	the exposed, antigenic, GH loop	249:279	the exposed, antigenic, GH loop of capsid protein VP1	249:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	5	36	theme	hydrophobic	944:954	arg1	residues					956:963	downstream hydrophobic residues	933:963	downstream hydrophobic residues	933:963	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	6	37	theme	HS	1051:1052	arg1	site					1062:1065	the previously identified HS binding site	1025:1065	the previously identified HS binding site	1025:1065	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	2	38	theme	basic	401:405	arg1	mutations					407:415	acquired basic mutations	392:415	acquired basic mutations interacting with heparin sulphate (HS)	392:454	Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections.
28534487	1	39	from	motif	240:244	arg1	loop					276:279	the exposed, antigenic, GH loop	249:279	the exposed, antigenic, GH loop of capsid protein VP1	249:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	3	40	theme	sulfated-sugar	605:618	arg1	binding					620:626	sulfated-sugar binding	605:626	sulfated-sugar binding	605:626	HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding.
28534487	5	41	theme	high	843:846	arg1	resolution					848:857	high resolution	843:857	high resolution	843:857	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	1	42	theme	cell	121:124	arg1	entry					126:130	cell entry	121:130	cell entry	121:130	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	1	43	theme	conserved	193:201	arg1	motif					240:244	a conserved arginine-glycine-aspartic acid (RGD) motif	191:244	a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1	191:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	4	44	theme	cryo-electron	724:736	arg1	microscopy					738:747	cryo-electron microscopy	724:747	cryo-electron microscopy	724:747	Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy.
28534487	1	45	theme	arginine-glycine-aspartic	203:227	arg1	acid					229:232	arginine-glycine-aspartic acid	203:232	a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1	191:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	1	45	theme	arginine-glycine-aspartic	203:227	arg1	RGD					235:237	RGD	235:237	RGD	235:237	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	5	46	theme	RGD	918:920	arg1	motif					922:926	the RGD motif	914:926	the RGD motif	914:926	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	5	47	theme	engagement	775:784	arg1	mode					767:770	the preferred mode	753:770	the preferred mode of engagement	753:784	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	5	48	theme	integrin	814:821	arg1	form					802:805	the fully open form	787:805	the fully open form	787:805	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	1	49	theme	acid	229:232	arg1	motif					240:244	a conserved arginine-glycine-aspartic acid (RGD) motif	191:244	a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1	191:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	0	50	theme	disease	61:67	arg1	virus					69:73	foot-and-mouth disease virus	46:73	foot-and-mouth disease virus	46:73	Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus.
28534487	1	51	theme	capsid	284:289	arg1	VP1					299:301	capsid protein VP1	284:301	capsid protein VP1	284:301	Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1.
28534487	3	52	theme	conserved	545:553	arg1	site					555:558	a conserved site	543:558	a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding	543:626	HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding.
28534487	6	53	link	N-linked	982:989	arg1	sugar					991:995	an N-linked sugar	979:995	an N-linked sugar of the integrin	979:1011	In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.
28534487	5	54	attach	attaches	860:867	arg1	loop					887:890	an extended GH loop	872:890	an extended GH loop	872:890	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28534487	5	54	attach	attaches	860:867	arg2	form					802:805	the fully open form	787:805	the fully open form	787:805	In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues.
28511131	8	0	theme	N-linked	1420:1427	arg1	analysis					1454:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	4	1	located	observed	810:817	arg2	isolates					796:803	eight RespPRRSV MLV vaccine-like isolates	763:803	eight RespPRRSV MLV vaccine-like isolates	763:803	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	4	1	located	observed	810:817	arg1	subgroup					822:829	subgroup 3	822:831	subgroup 3	822:831	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	4	1	located	observed	810:817	arg2	isolates					728:735	Highly pathogenic PRRSV (HP-PRRSV) isolates	693:735	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan	693:757	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	8	2	theme	acid	1507:1510	arg1	position					1512:1519	GP5 amino acid position 59	1497:1522	GP5 amino acid position 59 in two of the subgroup 2 Henan isolates	1497:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	9	3	gly	glycosylation	1676:1688	arg2	crucial					1715:1721	crucial	1715:1721	crucial	1715:1721	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	3	gly	glycosylation	1676:1688	arg2	site					1690:1693	a glycosylation site	1674:1693	a glycosylation site that is known to be crucial for PRRSV infectivity	1674:1743	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	8	4	theme	isolates	1555:1562	arg1	two					1527:1529	two	1527:1529	two	1527:1529	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	8	4	theme	isolates	1555:1562	arg1	isolates					1555:1562	the subgroup 2 Henan isolates	1534:1562	the subgroup 2 Henan isolates	1534:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	1	5	theme	Henan	241:245	arg1	province					247:254	Henan province	241:254	Henan province of China	241:263	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	7	6	theme	amino	1380:1384	arg1	acids					1386:1390	amino acids 77 and 82	1380:1400	acids	1386:1390	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	9	7	theme	PRRSV	1727:1731	arg1	infectivity					1733:1743	PRRSV infectivity	1727:1743	PRRSV infectivity	1727:1743	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	6	8	dep	vaccine	1095:1101	arg1	isolate					1103:1109	isolate	1103:1109	isolate	1103:1109	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	9	9	theme	Henan	1646:1650	arg1	isolate					1652:1658	a single subgroup 1 Henan isolate	1626:1658	a single subgroup 1 Henan isolate (HeNan-A9)	1626:1669	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	9	theme	Henan	1646:1650	arg1	HeNan-A9					1661:1668	HeNan-A9	1661:1668	HeNan-A9	1661:1668	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	6	10	theme	amino	1174:1178	arg1	acid					1180:1183	amino acid 39	1174:1186	amino acid 39	1174:1186	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	5	11	theme	variation	843:851	arg1	analysis					853:860	Sequence variation analysis	834:860	Sequence variation analysis	834:860	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	9	12	theme	novel	1573:1577	arg1	44N→44D					1604:1610	44N→44D	1604:1610	44N→44D	1604:1610	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	12	theme	novel	1573:1577	arg1	mutation					1594:1601	Another novel GP5 amino acid mutation	1565:1601	Another novel GP5 amino acid mutation (44N→44D)	1565:1611	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	1	13	theme	syndrome	215:222	arg1	virus					224:228	prevailing porcine reproductive and respiratory syndrome virus	167:228	virus	224:228	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	9	14	theme	amino	1583:1587	arg1	44N→44D					1604:1610	44N→44D	1604:1610	44N→44D	1604:1610	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	14	theme	amino	1583:1587	arg1	mutation					1594:1601	Another novel GP5 amino acid mutation	1565:1601	Another novel GP5 amino acid mutation (44N→44D)	1565:1611	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	8	15	theme	site	1443:1446	arg1	analysis					1454:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	5	16	with	nucleotide	927:936	arg1	other					988:992	other	988:992	other	988:992	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	8	17	from	position	1512:1519	arg1	isolates					1555:1562	the subgroup 2 Henan isolates	1534:1562	the subgroup 2 Henan isolates	1534:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	8	17	from	position	1512:1519	arg1	NGS					1490:1492	a novel potential NGS	1472:1492	a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates	1472:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	8	17	from	position	1512:1519	arg1	two					1527:1529	two	1527:1529	two	1527:1529	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	1	18	theme	sequence	376:383	arg1	variation					385:393	sequence variation	376:393	sequence variation	376:393	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	6	19	theme	Henan	1142:1146	arg1	isolates					1148:1155	the subgroup 1 Henan isolates	1127:1155	the subgroup 1 Henan isolates	1127:1155	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	6	20	theme	GP5	1210:1212	arg1	PNE					1203:1205	the key PNE	1195:1205	the key PNE of GP5	1195:1212	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	7	21	theme	motif	1272:1276	arg1	Analysis					1215:1222	Analysis	1215:1222	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5	1215:1290	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	0	22	theme	gene	56:59	arg1	diversity					8:16	Genetic diversity	0:16	Genetic diversity	0:16	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	0	22	theme	gene	56:59	arg1	analysis					35:42	phylogenetic analysis	22:42	phylogenetic analysis	22:42	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	1	23	from	epidemiology	151:162	arg1	province					247:254	Henan province	241:254	Henan province of China	241:263	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	0	24	theme	PRRSV	64:68	arg1	gene					56:59	the ORF5 gene	47:59	the ORF5 gene of PRRSV from central China	47:87	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	1	25	theme	Henan	320:324	arg1	province					326:333	Henan province	320:333	Henan province between 2006 and 2015	320:355	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	1	26	theme	molecular	141:149	arg1	epidemiology					151:162	molecular epidemiology	141:162	molecular epidemiology	141:162	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	1	27	dep	diversity	127:135	arg1	the					115:117	the	115:117	the	115:117	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	0	28	theme	central	75:81	arg1	China					83:87	central China	75:87	central China	75:87	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	7	29	from	motif	1272:1276	arg1	GP5					1288:1290	GP5	1288:1290	GP5	1288:1290	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	9	30	theme	single	1628:1633	arg1	isolate					1652:1658	a single subgroup 1 Henan isolate	1626:1658	a single subgroup 1 Henan isolate (HeNan-A9)	1626:1669	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	30	theme	single	1628:1633	arg1	HeNan-A9					1661:1668	HeNan-A9	1661:1668	HeNan-A9	1661:1668	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	7	31	theme	inhibitory	1261:1270	arg1	ITIM					1279:1282	ITIM	1279:1282	ITIM	1279:1282	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	7	31	theme	inhibitory	1261:1270	arg1	motif					1272:1276	the immunoreceptor tyrosine-based inhibitory motif	1227:1276	the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5	1227:1290	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	0	32	from	analysis	35:42	arg1	China					83:87	central China	75:87	central China	75:87	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	4	33	theme	pathogenic	700:709	arg1	isolates					728:735	Highly pathogenic PRRSV (HP-PRRSV) isolates	693:735	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan	693:757	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	0	34	theme	Genetic	0:6	arg1	diversity					8:16	Genetic diversity	0:16	Genetic diversity	0:16	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	1	35	theme	China	259:263	arg1	province					247:254	Henan province	241:254	Henan province of China	241:263	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	5	36	theme	isolates	904:911	arg1	genes					885:889	the ORF5 genes	876:889	the ORF5 genes of all Henan isolates	876:911	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	7	37	theme	immunoreceptor	1231:1244	arg1	ITIM					1279:1282	ITIM	1279:1282	ITIM	1279:1282	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	7	37	theme	immunoreceptor	1231:1244	arg1	motif					1272:1276	the immunoreceptor tyrosine-based inhibitory motif	1227:1276	the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5	1227:1290	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	6	38	contain	had	1157:1159	arg2	mutations					1161:1169	mutations	1161:1169	mutations at amino acid 39	1161:1186	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	6	38	contain	had	1157:1159	arg1	one					1120:1122	one	1120:1122	one	1120:1122	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	6	38	contain	had	1157:1159	arg1	isolates					1148:1155	the subgroup 1 Henan isolates	1127:1155	the subgroup 1 Henan isolates	1127:1155	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	6	38	contain	had	1157:1159	arg1	all					1112:1114	all	1112:1114	all	1112:1114	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	5	39	theme	>83.3	920:924	arg1	%					925:925	%	925:925	%	925:925	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	6	40	theme	neutralizing	1003:1014	arg1	PNE					1025:1027	PNE	1025:1027	PNE	1025:1027	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	6	40	theme	neutralizing	1003:1014	arg1	epitope					1016:1022	Primary neutralizing epitope	995:1022	Primary neutralizing epitope (PNE) analysis	995:1037	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	2	41	theme	Henan	462:466	arg1	isolates					468:475	all Henan isolates	458:475	all Henan isolates	458:475	Phylogenetic analysis revealed that all Henan isolates belonged to the Type 2 genotype and could be further divided into three subgroups.
28511131	8	42	theme	NGS	1449:1451	arg1	analysis					1454:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	3	43	theme	overtook	622:629	arg1	subgroup					631:638	subgroup 2 overtook subgroup 1	611:640	subgroup 2 overtook subgroup 1	611:640	Subgroup 1 and 2 viruses predominated in Henan and subgroup 2 overtook subgroup 1 as the most prevalent PRRSV between 2006 and 2015.
28511131	4	44	theme	MLV	779:781	arg1	isolates					796:803	eight RespPRRSV MLV vaccine-like isolates	763:803	eight RespPRRSV MLV vaccine-like isolates	763:803	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	1	45	theme	ORF5	282:285	arg1	sequences					292:300	112 full-length ORF5 gene sequences	266:300	112 full-length ORF5 gene sequences	266:300	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	7	46	theme	GP5	1415:1417	arg1	positions					1402:1410	amino acids 77 and 82 positions	1380:1410	amino acids 77 and 82 positions of GP5	1380:1417	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	3	47	theme	subgroup	611:618	arg1	subgroup					631:638	subgroup 2 overtook subgroup 1	611:640	subgroup 2 overtook subgroup 1	611:640	Subgroup 1 and 2 viruses predominated in Henan and subgroup 2 overtook subgroup 1 as the most prevalent PRRSV between 2006 and 2015.
28511131	7	48	contain	had	1340:1342	arg1	two					1314:1316	two	1314:1316	two	1314:1316	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	7	48	contain	had	1340:1342	arg1	isolates					1331:1338	the Henan isolates	1321:1338	the Henan isolates	1321:1338	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	7	48	contain	had	1340:1342	arg1	all					1306:1308	all	1306:1308	all	1306:1308	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	7	48	contain	had	1340:1342	arg2	sequence					1363:1370	a highly conserved sequence	1344:1370	a highly conserved sequence between amino acids 77 and 82 positions of GP5	1344:1417	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	7	49	from	Analysis	1215:1222	arg1	GP5					1288:1290	GP5	1288:1290	GP5	1288:1290	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	6	50	theme	attenuated	1070:1079	arg1	vaccine					1095:1101	the attenuated RespPRRSV MLV vaccine isolate	1066:1109	the attenuated RespPRRSV MLV vaccine isolate	1066:1109	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	9	51	theme	glycosylation	1676:1688	arg1	site					1690:1693	a glycosylation site	1674:1693	a glycosylation site that is known to be crucial for PRRSV infectivity	1674:1743	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	51	theme	glycosylation	1676:1688	arg1	crucial					1715:1721	crucial	1715:1721	crucial	1715:1721	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	1	52	theme	virus	224:228	arg1	diversity					127:135	genetic diversity	119:135	genetic diversity	119:135	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	1	52	theme	virus	224:228	arg1	epidemiology					151:162	molecular epidemiology	141:162	molecular epidemiology	141:162	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	5	53	theme	amino	949:953	arg1	identity					969:976	>83.3% nucleotide and >80.1% amino acid sequence identity	920:976	identity	969:976	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	8	54	theme	potential	1480:1488	arg1	NGS					1490:1492	a novel potential NGS	1472:1492	a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates	1472:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	1	55	dep	reproductive	186:197	arg1	prevailing					167:176	prevailing	167:176	prevailing	167:176	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	7	56	theme	acids	1386:1390	arg1	positions					1402:1410	amino acids 77 and 82 positions	1380:1410	amino acids 77 and 82 positions of GP5	1380:1417	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	5	57	theme	sequence	960:967	arg1	identity					969:976	>83.3% nucleotide and >80.1% amino acid sequence identity	920:976	identity	969:976	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	8	58	link	N-linked	1420:1427	arg1	analysis					1454:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	8	59	theme	subgroup	1538:1545	arg1	isolates					1555:1562	the subgroup 2 Henan isolates	1534:1562	the subgroup 2 Henan isolates	1534:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	6	60	from	acid	1180:1183	arg1	mutations					1161:1169	mutations	1161:1169	mutations at amino acid 39	1161:1186	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	8	61	theme	amino	1501:1505	arg1	position					1512:1519	GP5 amino acid position 59	1497:1522	GP5 amino acid position 59 in two of the subgroup 2 Henan isolates	1497:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	3	62	theme	prevalent	654:662	arg1	PRRSV					664:668	the most prevalent PRRSV	645:668	the most prevalent PRRSV between 2006 and 2015	645:690	Subgroup 1 and 2 viruses predominated in Henan and subgroup 2 overtook subgroup 1 as the most prevalent PRRSV between 2006 and 2015.
28511131	6	63	theme	key	1199:1201	arg1	PNE					1203:1205	the key PNE	1195:1205	the key PNE of GP5	1195:1212	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	8	64	theme	Henan	1549:1553	arg1	isolates					1555:1562	the subgroup 2 Henan isolates	1534:1562	the subgroup 2 Henan isolates	1534:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	7	65	theme	conserved	1353:1361	arg1	sequence					1363:1370	a highly conserved sequence	1344:1370	a highly conserved sequence between amino acids 77 and 82 positions of GP5	1344:1417	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	5	66	with	identity	969:976	arg1	other					988:992	other	988:992	other	988:992	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	7	67	theme	Henan	1325:1329	arg1	isolates					1331:1338	the Henan isolates	1321:1338	the Henan isolates	1321:1338	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	5	68	theme	Sequence	834:841	arg1	analysis					853:860	Sequence variation analysis	834:860	Sequence variation analysis	834:860	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	6	69	theme	subgroup	1131:1138	arg1	isolates					1148:1155	the subgroup 1 Henan isolates	1127:1155	the subgroup 1 Henan isolates	1127:1155	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	1	70	theme	reproductive	186:197	arg1	diversity					127:135	genetic diversity	119:135	genetic diversity	119:135	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	1	70	theme	reproductive	186:197	arg1	epidemiology					151:162	molecular epidemiology	141:162	molecular epidemiology	141:162	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	8	71	gly	glycosylation	1429:1441	arg2	site					1443:1446	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	8	71	gly	glycosylation	1429:1441	arg2	analysis					1454:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	1	72	theme	respiratory	203:213	arg1	virus					224:228	prevailing porcine reproductive and respiratory syndrome virus	167:228	virus	224:228	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	9	73	theme	GP5	1579:1581	arg1	44N→44D					1604:1610	44N→44D	1604:1610	44N→44D	1604:1610	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	73	theme	GP5	1579:1581	arg1	mutation					1594:1601	Another novel GP5 amino acid mutation	1565:1601	Another novel GP5 amino acid mutation (44N→44D)	1565:1611	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	5	74	theme	ORF5	880:883	arg1	genes					885:889	the ORF5 genes	876:889	the ORF5 genes of all Henan isolates	876:911	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	9	75	theme	acid	1589:1592	arg1	44N→44D					1604:1610	44N→44D	1604:1610	44N→44D	1604:1610	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	75	theme	acid	1589:1592	arg1	mutation					1594:1601	Another novel GP5 amino acid mutation	1565:1601	Another novel GP5 amino acid mutation (44N→44D)	1565:1611	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	0	76	from	China	83:87	arg1	gene					56:59	the ORF5 gene	47:59	the ORF5 gene of PRRSV from central China	47:87	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	0	76	from	China	83:87	arg1	diversity					8:16	Genetic diversity	0:16	Genetic diversity	0:16	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	0	76	from	China	83:87	arg1	analysis					35:42	phylogenetic analysis	22:42	phylogenetic analysis	22:42	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	1	77	theme	phylogenetic	399:410	arg1	analysis					412:419	phylogenetic analysis	399:419	phylogenetic analysis	399:419	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	1	78	theme	genetic	119:125	arg1	diversity					127:135	genetic diversity	119:135	genetic diversity	119:135	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	0	79	from	diversity	8:16	arg1	China					83:87	central China	75:87	central China	75:87	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	5	80	theme	%	925:925	arg1	nucleotide					927:936	>83.3% nucleotide and >80.1% amino acid sequence identity	920:976	nucleotide	927:936	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	6	81	theme	MLV	1091:1093	arg1	vaccine					1095:1101	the attenuated RespPRRSV MLV vaccine isolate	1066:1109	the attenuated RespPRRSV MLV vaccine isolate	1066:1109	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	4	82	theme	HP-PRRSV	718:725	arg1	isolates					728:735	Highly pathogenic PRRSV (HP-PRRSV) isolates	693:735	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan	693:757	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	1	83	from	diversity	127:135	arg1	province					247:254	Henan province	241:254	Henan province of China	241:263	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	9	84	located	found	1617:1621	arg1	isolate					1652:1658	a single subgroup 1 Henan isolate	1626:1658	a single subgroup 1 Henan isolate (HeNan-A9)	1626:1669	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	84	located	found	1617:1621	arg1	site					1690:1693	a glycosylation site	1674:1693	a glycosylation site that is known to be crucial for PRRSV infectivity	1674:1743	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	84	located	found	1617:1621	arg2	44N→44D					1604:1610	44N→44D	1604:1610	44N→44D	1604:1610	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	84	located	found	1617:1621	arg1	HeNan-A9					1661:1668	HeNan-A9	1661:1668	HeNan-A9	1661:1668	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	84	located	found	1617:1621	arg2	mutation					1594:1601	Another novel GP5 amino acid mutation	1565:1601	Another novel GP5 amino acid mutation (44N→44D)	1565:1611	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	84	located	found	1617:1621	arg1	crucial					1715:1721	crucial	1715:1721	crucial	1715:1721	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	7	85	theme	tyrosine-based	1246:1259	arg1	ITIM					1279:1282	ITIM	1279:1282	ITIM	1279:1282	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	7	85	theme	tyrosine-based	1246:1259	arg1	motif					1272:1276	the immunoreceptor tyrosine-based inhibitory motif	1227:1276	the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5	1227:1290	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	2	86	theme	Type	493:496	arg1	genotype					500:507	the Type 2 genotype	489:507	the Type 2 genotype	489:507	Phylogenetic analysis revealed that all Henan isolates belonged to the Type 2 genotype and could be further divided into three subgroups.
28511131	8	87	theme	glycosylation	1429:1441	arg1	analysis					1454:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis	1420:1461	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	5	88	theme	Henan	898:902	arg1	isolates					904:911	all Henan isolates	894:911	all Henan isolates	894:911	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	2	89	theme	Phylogenetic	422:433	arg1	analysis					435:442	Phylogenetic analysis	422:442	Phylogenetic analysis	422:442	Phylogenetic analysis revealed that all Henan isolates belonged to the Type 2 genotype and could be further divided into three subgroups.
28511131	0	90	theme	phylogenetic	22:33	arg1	analysis					35:42	phylogenetic analysis	22:42	phylogenetic analysis	22:42	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	7	91	from	GP5	1288:1290	arg1	Analysis					1215:1222	Analysis	1215:1222	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5	1215:1290	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	6	92	theme	epitope	1016:1022	arg1	analysis					1030:1037	Primary neutralizing epitope (PNE) analysis	995:1037	Primary neutralizing epitope (PNE) analysis	995:1037	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	4	93	theme	PRRSV	711:715	arg1	isolates					728:735	Highly pathogenic PRRSV (HP-PRRSV) isolates	693:735	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan	693:757	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	1	94	theme	full-length	270:280	arg1	sequences					292:300	112 full-length ORF5 gene sequences	266:300	112 full-length ORF5 gene sequences	266:300	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	6	95	theme	Primary	995:1001	arg1	PNE					1025:1027	PNE	1025:1027	PNE	1025:1027	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	6	95	theme	Primary	995:1001	arg1	epitope					1016:1022	Primary neutralizing epitope	995:1022	Primary neutralizing epitope (PNE) analysis	995:1037	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	4	96	theme	RespPRRSV	769:777	arg1	isolates					796:803	eight RespPRRSV MLV vaccine-like isolates	763:803	eight RespPRRSV MLV vaccine-like isolates	763:803	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	9	97	theme	subgroup	1635:1642	arg1	isolate					1652:1658	a single subgroup 1 Henan isolate	1626:1658	a single subgroup 1 Henan isolate (HeNan-A9)	1626:1669	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	9	97	theme	subgroup	1635:1642	arg1	HeNan-A9					1661:1668	HeNan-A9	1661:1668	HeNan-A9	1661:1668	Another novel GP5 amino acid mutation (44N→44D) was found in a single subgroup 1 Henan isolate (HeNan-A9) in a glycosylation site that is known to be crucial for PRRSV infectivity.
28511131	0	98	theme	ORF5	51:54	arg1	gene					56:59	the ORF5 gene	47:59	the ORF5 gene of PRRSV from central China	47:87	Genetic diversity and phylogenetic analysis of the ORF5 gene of PRRSV from central China.
28511131	1	99	theme	gene	287:290	arg1	sequences					292:300	112 full-length ORF5 gene sequences	266:300	112 full-length ORF5 gene sequences	266:300	To more fully understand the genetic diversity and molecular epidemiology of prevailing porcine reproductive and respiratory syndrome virus (PRRSV) in Henan province of China, 112 full-length ORF5 gene sequences, originating from Henan province between 2006 and 2015, were subjected to sequence variation and phylogenetic analysis.
28511131	6	100	theme	RespPRRSV	1081:1089	arg1	vaccine					1095:1101	the attenuated RespPRRSV MLV vaccine isolate	1066:1109	the attenuated RespPRRSV MLV vaccine isolate	1066:1109	Primary neutralizing epitope (PNE) analysis revealed that, relative to the attenuated RespPRRSV MLV vaccine isolate, all but one of the subgroup 1 Henan isolates had mutations at amino acid 39 within the key PNE of GP5.
28511131	8	101	theme	novel	1474:1478	arg1	NGS					1490:1492	a novel potential NGS	1472:1492	a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates	1472:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28511131	4	102	theme	vaccine-like	783:794	arg1	isolates					796:803	eight RespPRRSV MLV vaccine-like isolates	763:803	eight RespPRRSV MLV vaccine-like isolates	763:803	Highly pathogenic PRRSV (HP-PRRSV) isolates predominated in Henan and eight RespPRRSV MLV vaccine-like isolates were observed in subgroup 3.
28511131	5	103	theme	%	947:947	arg1	identity					969:976	>83.3% nucleotide and >80.1% amino acid sequence identity	920:976	identity	969:976	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	7	104	theme	82	1399:1400	arg1	positions					1402:1410	amino acids 77 and 82 positions	1380:1410	amino acids 77 and 82 positions of GP5	1380:1417	Analysis of the immunoreceptor tyrosine-based inhibitory motif (ITIM) in GP5 revealed that all but two of the Henan isolates had a highly conserved sequence between amino acids 77 and 82 positions of GP5.
28511131	5	105	theme	acid	955:958	arg1	identity					969:976	>83.3% nucleotide and >80.1% amino acid sequence identity	920:976	identity	969:976	Sequence variation analysis revealed that the ORF5 genes of all Henan isolates shared >83.3% nucleotide and >80.1% amino acid sequence identity with each other.
28511131	8	106	theme	GP5	1497:1499	arg1	position					1512:1519	GP5 amino acid position 59	1497:1522	GP5 amino acid position 59 in two of the subgroup 2 Henan isolates	1497:1562	N-linked glycosylation site (NGS) analysis revealed a novel potential NGS at GP5 amino acid position 59 in two of the subgroup 2 Henan isolates.
28490633	0	0	theme	selectivity	105:115	arg1	mechanism					117:125	a selectivity mechanism	103:125	a selectivity mechanism for misfolded proteins	103:148	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	8	1	used	used	1127:1130	arg2	We					1119:1120	We	1119:1120	We	1119:1120	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	8	2	theme	hydrogen-deuterium	1132:1149	arg1	spectrometry					1165:1176	hydrogen-deuterium exchange mass spectrometry	1132:1176	hydrogen-deuterium exchange mass spectrometry	1132:1176	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	10	3	theme	exposed	1467:1473	arg1	residues					1487:1494	exposed hydrophobic residues	1467:1494	exposed hydrophobic residues	1467:1494	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	7	4	theme	sites	988:992	arg1	Introduction					958:969	Introduction	958:969	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli	958:1041	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli allowed identification of the catalytic and first thioredoxin-like domains.
28490633	11	5	theme	plausible	1636:1644	arg1	model					1657:1661	a plausible functional model	1634:1661	a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins	1634:1729	In conclusion, we have determined the UGGT structure, which enabled us to develop a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins.
28490633	9	6	theme	hydrophobic	1390:1400	arg1	surfaces					1402:1409	hydrophobic surfaces	1390:1409	hydrophobic surfaces	1390:1409	The UGGT structural features identified suggest that the central cavity contains the catalytic site and is lined with hydrophobic surfaces.
28490633	10	7	theme	substrates	1451:1460	arg1	binding					1430:1436	the binding	1426:1436	the binding of misfolded substrates with exposed hydrophobic residues	1426:1494	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	2	8	theme	misfolded	379:387	arg1	proteins					389:396	misfolded proteins	379:396	misfolded proteins	379:396	As a sensor, UGGT ensures that misfolded proteins are recognized by the lectin chaperones and do not leave the secretory pathway.
28490633	5	9	theme	Three-dimensional	758:774	arg1	reconstructions					776:790	Three-dimensional reconstructions	758:790	Three-dimensional reconstructions	758:790	Three-dimensional reconstructions revealed a cage-like structure with a large central cavity.
28490633	8	10	theme	mass	1160:1163	arg1	spectrometry					1165:1176	hydrogen-deuterium exchange mass spectrometry	1132:1176	hydrogen-deuterium exchange mass spectrometry	1132:1176	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	1	11	link	N-linked	309:316	arg1	glycan					318:323	N-linked glycan	309:323	N-linked glycan of misfolded proteins	309:345	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	11	12	theme	functional	1646:1655	arg1	model					1657:1661	a plausible functional model	1634:1661	a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins	1634:1729	In conclusion, we have determined the UGGT structure, which enabled us to develop a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins.
28490633	8	13	theme	thioredoxin-like	1247:1262	arg1	domain					1264:1269	the first thioredoxin-like domain	1237:1269	the first thioredoxin-like domain	1237:1269	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	8	14	theme	exchange	1151:1158	arg1	spectrometry					1165:1176	hydrogen-deuterium exchange mass spectrometry	1132:1176	hydrogen-deuterium exchange mass spectrometry	1132:1176	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	8	15	theme	protein	1218:1224	arg1	protein					1218:1224	an accessory protein	1205:1224	an accessory protein	1205:1224	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	8	15	theme	protein	1218:1224	arg1	site					1197:1200	the binding site	1185:1200	the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain	1185:1269	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	1	16	dep	UDP-glucose	162:172	arg1	mediates					214:221	mediates	214:221	mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins	214:345	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	1	17	theme	N-linked	309:316	arg1	glycan					318:323	N-linked glycan	309:323	N-linked glycan of misfolded proteins	309:345	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	4	18	theme	small-angle	645:655	arg1	scattering					663:672	small-angle X-ray scattering	645:672	small-angle X-ray scattering	645:672	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
28490633	0	19	theme	misfolded	131:139	arg1	proteins					141:148	misfolded proteins	131:148	misfolded proteins	131:148	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	5	20	theme	large	830:834	arg1	cavity					844:849	a large central cavity	828:849	a large central cavity	828:849	Three-dimensional reconstructions revealed a cage-like structure with a large central cavity.
28490633	4	21	theme	negative-stain	606:619	arg1	microscopy					630:639	negative-stain electron microscopy	606:639	negative-stain electron microscopy	606:639	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
28490633	2	22	theme	lectin	420:425	arg1	chaperones					427:436	the lectin chaperones	416:436	the lectin chaperones	416:436	As a sensor, UGGT ensures that misfolded proteins are recognized by the lectin chaperones and do not leave the secretory pathway.
28490633	0	23	theme	electron	16:23	arg1	microscopy					25:34	Single-particle electron microscopy	0:34	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase	0:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	10	24	with	proteins	1516:1523	arg1	surfaces					1542:1549	hydrophilic surfaces	1530:1549	hydrophilic surfaces	1530:1549	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	10	25	with	binding	1430:1436	arg1	residues					1487:1494	exposed hydrophobic residues	1467:1494	exposed hydrophobic residues	1467:1494	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	8	26	theme	accessory	1208:1216	arg1	protein					1218:1224	an accessory protein	1205:1224	an accessory protein	1205:1224	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	8	26	theme	accessory	1208:1216	arg1	Sep15					1227:1231	Sep15	1227:1231	Sep15	1227:1231	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	0	27	theme	Single-particle	0:14	arg1	microscopy					25:34	Single-particle electron microscopy	0:34	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase	0:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	9	28	theme	structural	1281:1290	arg1	features					1292:1299	The UGGT structural features	1272:1299	The UGGT structural features identified	1272:1310	The UGGT structural features identified suggest that the central cavity contains the catalytic site and is lined with hydrophobic surfaces.
28490633	1	29	gly	glycoproteins	242:254	arg1	glycoproteins					242:254	glycoproteins	242:254	glycoproteins	242:254	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	11	30	theme	mechanism	1670:1678	arg1	model					1657:1661	a plausible functional model	1634:1661	a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins	1634:1729	In conclusion, we have determined the UGGT structure, which enabled us to develop a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins.
28490633	10	31	theme	misfolded	1441:1449	arg1	substrates					1451:1460	misfolded substrates	1441:1460	misfolded substrates	1441:1460	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	8	32	theme	first	1241:1245	arg1	domain					1264:1269	the first thioredoxin-like domain	1237:1269	the first thioredoxin-like domain	1237:1269	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	1	33	theme	quality	223:229	arg1	control					231:237	quality control	223:237	quality control of glycoproteins	223:254	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	2	34	theme	secretory	459:467	arg1	pathway					469:475	the secretory pathway	455:475	the secretory pathway	455:475	As a sensor, UGGT ensures that misfolded proteins are recognized by the lectin chaperones and do not leave the secretory pathway.
28490633	6	35	theme	Particle	852:859	arg1	classification					861:874	Particle classification	852:874	Particle classification	852:874	Particle classification revealed flexibility that precluded determination of a high-resolution structure.
28490633	7	36	theme	thioredoxin-like	1093:1108	arg1	domains					1110:1116	first thioredoxin-like domains	1087:1116	first thioredoxin-like domains	1087:1116	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli allowed identification of the catalytic and first thioredoxin-like domains.
28490633	4	37	theme	X-ray	657:661	arg1	scattering					663:672	small-angle X-ray scattering	645:672	small-angle X-ray scattering	645:672	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
28490633	0	38	theme	microscopy	25:34	arg1	structure					36:44	Single-particle electron microscopy structure	0:44	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase	0:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	1	39	theme	misfolded	328:336	arg1	proteins					338:345	misfolded proteins	328:345	misfolded proteins	328:345	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	8	40	theme	binding	1189:1195	arg1	protein					1218:1224	an accessory protein	1205:1224	an accessory protein	1205:1224	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	8	40	theme	binding	1189:1195	arg1	site					1197:1200	the binding site	1185:1200	the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain	1185:1269	We also used hydrogen-deuterium exchange mass spectrometry to map the binding site of an accessory protein, Sep15, to the first thioredoxin-like domain.
28490633	3	41	theme	selectivity	525:535	arg1	mechanism					508:516	the mechanism	504:516	the mechanism of its selectivity for misfolded proteins	504:558	The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years.
28490633	3	41	theme	selectivity	525:535	arg1	structure					482:490	The structure	478:490	The structure of UGGT	478:498	The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years.
28490633	3	41	theme	selectivity	525:535	arg1	unknown					570:576	unknown	570:576	unknown	570:576	The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years.
28490633	3	42	theme	UGGT	495:498	arg1	mechanism					508:516	the mechanism	504:516	the mechanism of its selectivity for misfolded proteins	504:558	The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years.
28490633	3	42	theme	UGGT	495:498	arg1	structure					482:490	The structure	478:490	The structure of UGGT	478:498	The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years.
28490633	3	42	theme	UGGT	495:498	arg1	unknown					570:576	unknown	570:576	unknown	570:576	The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years.
28490633	0	43	theme	UDP-glucose	49:59	arg1	structure					36:44	Single-particle electron microscopy structure	0:44	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase	0:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	1	44	theme	proteins	338:345	arg1	glycan					318:323	N-linked glycan	309:323	N-linked glycan of misfolded proteins	309:345	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	6	45	theme	structure	947:955	arg1	determination					912:924	determination	912:924	determination of a high-resolution structure	912:955	Particle classification revealed flexibility that precluded determination of a high-resolution structure.
28490633	1	46	theme	glycoproteins	242:254	arg1	control					231:237	quality control	223:237	quality control of glycoproteins	223:254	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	5	47	theme	central	836:842	arg1	cavity					844:849	a large central cavity	828:849	a large central cavity	828:849	Three-dimensional reconstructions revealed a cage-like structure with a large central cavity.
28490633	6	48	theme	high-resolution	931:945	arg1	structure					947:955	a high-resolution structure	929:955	a high-resolution structure	929:955	Particle classification revealed flexibility that precluded determination of a high-resolution structure.
28490633	11	49	theme	misfolded	1707:1715	arg1	glycoproteins					1717:1729	misfolded glycoproteins	1707:1729	misfolded glycoproteins	1707:1729	In conclusion, we have determined the UGGT structure, which enabled us to develop a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins.
28490633	0	50	theme	glycoprotein	61:72	arg1	glucosyltransferase					74:92	glycoprotein glucosyltransferase	61:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase	0:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	1	51	gly	glycoprotein	174:185	arg1	glycoprotein					174:185	glycoprotein glucosyltransferase	174:205	glycoprotein glucosyltransferase (UGGT)	174:212	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	9	52	theme	catalytic	1357:1365	arg1	site					1367:1370	the catalytic site	1353:1370	the catalytic site	1353:1370	The UGGT structural features identified suggest that the central cavity contains the catalytic site and is lined with hydrophobic surfaces.
28490633	9	53	theme	central	1329:1335	arg1	cavity					1337:1342	the central cavity	1325:1342	the central cavity	1325:1342	The UGGT structural features identified suggest that the central cavity contains the catalytic site and is lined with hydrophobic surfaces.
28490633	4	54	theme	18-Å	741:744	arg1	resolution					746:755	18-Å resolution	741:755	18-Å resolution	741:755	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
28490633	4	55	used	used	601:604	arg2	we					598:599	we	598:599	we	598:599	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
28490633	11	56	gly	glycoproteins	1717:1729	arg1	glycoproteins					1717:1729	misfolded glycoproteins	1707:1729	misfolded glycoproteins	1707:1729	In conclusion, we have determined the UGGT structure, which enabled us to develop a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins.
28490633	7	57	theme	domains	1110:1116	arg1	identification					1051:1064	identification	1051:1064	identification of the catalytic and first thioredoxin-like domains	1051:1116	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli allowed identification of the catalytic and first thioredoxin-like domains.
28490633	7	58	theme	fungal	1001:1006	arg1	UGGT					1008:1011	a fungal UGGT	999:1011	a fungal UGGT expressed in Escherichia coli	999:1041	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli allowed identification of the catalytic and first thioredoxin-like domains.
28490633	5	59	with	structure	813:821	arg1	cavity					844:849	a large central cavity	828:849	a large central cavity	828:849	Three-dimensional reconstructions revealed a cage-like structure with a large central cavity.
28490633	0	60	dep	structure	36:44	arg1	glucosyltransferase					74:92	glycoprotein glucosyltransferase	61:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase	0:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	4	61	theme	UGGT	704:707	arg1	structure					691:699	the structure	687:699	the structure of UGGT from Drosophila melanogaster	687:736	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
28490633	1	62	theme	enzyme	155:160	arg1	UDP-glucose					162:172	The enzyme UDP-glucose	151:172	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.	151:346	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	10	63	theme	hydrophobic	1475:1485	arg1	residues					1487:1494	exposed hydrophobic residues	1467:1494	exposed hydrophobic residues	1467:1494	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	4	64	theme	electron	621:628	arg1	microscopy					630:639	negative-stain electron microscopy	606:639	negative-stain electron microscopy	606:639	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
28490633	7	65	theme	first	1087:1091	arg1	domains					1110:1116	first thioredoxin-like domains	1087:1116	first thioredoxin-like domains	1087:1116	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli allowed identification of the catalytic and first thioredoxin-like domains.
28490633	3	66	theme	misfolded	541:549	arg1	proteins					551:558	misfolded proteins	541:558	misfolded proteins	541:558	The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years.
28490633	9	67	contain	contains	1344:1351	arg1	cavity					1337:1342	the central cavity	1325:1342	the central cavity	1325:1342	The UGGT structural features identified suggest that the central cavity contains the catalytic site and is lined with hydrophobic surfaces.
28490633	9	67	contain	contains	1344:1351	arg2	site					1367:1370	the catalytic site	1353:1370	the catalytic site	1353:1370	The UGGT structural features identified suggest that the central cavity contains the catalytic site and is lined with hydrophobic surfaces.
28490633	1	68	theme	endoplasmic	263:273	arg1	reticulum					275:283	the endoplasmic reticulum	259:283	the endoplasmic reticulum	259:283	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	5	69	theme	cage-like	803:811	arg1	structure					813:821	a cage-like structure	801:821	a cage-like structure with a large central cavity	801:849	Three-dimensional reconstructions revealed a cage-like structure with a large central cavity.
28490633	7	70	theme	biotinylation	974:986	arg1	sites					988:992	biotinylation sites	974:992	biotinylation sites	974:992	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli allowed identification of the catalytic and first thioredoxin-like domains.
28490633	10	71	theme	folded	1509:1514	arg1	proteins					1516:1523	folded proteins	1509:1523	folded proteins with hydrophilic surfaces	1509:1549	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	11	72	theme	UGGT	1590:1593	arg1	structure					1595:1603	the UGGT structure	1586:1603	the UGGT structure	1586:1603	In conclusion, we have determined the UGGT structure, which enabled us to develop a plausible functional model of the mechanism for UGGT's selectivity for misfolded glycoproteins.
28490633	10	73	theme	hydrophilic	1530:1540	arg1	surfaces					1542:1549	hydrophilic surfaces	1530:1549	hydrophilic surfaces	1530:1549	This enhances the binding of misfolded substrates with exposed hydrophobic residues and excludes folded proteins with hydrophilic surfaces.
28490633	0	74	gly	glycoprotein	61:72	arg1	glycoprotein					61:72	glycoprotein glucosyltransferase	61:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase	0:92	Single-particle electron microscopy structure of UDP-glucose:glycoprotein glucosyltransferase suggests a selectivity mechanism for misfolded proteins.
28490633	7	75	theme	catalytic	1073:1081	arg1	identification					1051:1064	identification	1051:1064	identification of the catalytic and first thioredoxin-like domains	1051:1116	Introduction of biotinylation sites into a fungal UGGT expressed in Escherichia coli allowed identification of the catalytic and first thioredoxin-like domains.
28490633	1	76	theme	glycoprotein	174:185	arg1	UGGT					208:211	UGGT	208:211	UGGT	208:211	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	1	76	theme	glycoprotein	174:185	arg1	glucosyltransferase					187:205	glycoprotein glucosyltransferase	174:205	glycoprotein glucosyltransferase (UGGT)	174:212	The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins.
28490633	4	77	from	melanogaster	725:736	arg1	structure					691:699	the structure	687:699	the structure of UGGT from Drosophila melanogaster	687:736	Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18-Å resolution.
31563509	3	0	with	interactions	619:630	arg1	proteins					656:663	polytopic membrane proteins	637:663	polytopic membrane proteins	637:663	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	8	1	from	residue	1600:1606	arg1	helix					1634:1638	the reentrant membrane helix	1611:1638	the reentrant membrane helix	1611:1638	Geometry is found to be important for binding to PglC; a conserved proline residue in the reentrant membrane helix is determined to drive polyprenol phosphate recognition and specificity.
31563509	3	2	theme	polytopic	637:645	arg1	proteins					656:663	polytopic membrane proteins	637:663	polytopic membrane proteins	637:663	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	6	3	theme	Campylobacter	1350:1362	arg1	jejuni					1364:1369	Campylobacter jejuni	1350:1369	Campylobacter jejuni	1350:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	4	4	theme	monotopic	777:785	arg1	enzymes					815:821	monotopic phosphoglycosyl transferase enzymes	777:821	monotopic phosphoglycosyl transferase enzymes	777:821	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	2	5	theme	polytopic	379:387	arg1	proteins					398:405	polytopic membrane proteins	379:405	polytopic membrane proteins	379:405	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	5	theme	polytopic	379:387	arg1	phosphoglycosyl					439:453	phosphoglycosyl	439:453	phosphoglycosyl	439:453	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	5	theme	polytopic	379:387	arg1	transferases					468:479	glycosyl transferases	459:479	glycosyl transferases	459:479	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	1	6	theme	membrane-associated	231:249	arg1	pathways					279:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life.
31563509	10	7	with	interactions	2016:2027	arg1	proteins					2087:2094	diverse membrane-associated proteins	2059:2094	diverse membrane-associated proteins in glycoconjugate biosynthesis	2059:2125	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	9	8	theme	specific	1921:1928	arg1	geometries					1939:1948	specific isoprene geometries	1921:1948	specific isoprene geometries	1921:1948	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	10	9	theme	new	1999:2001	arg1	light					2003:2007	new light	1999:2007	new light	1999:2007	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	1	10	theme	biosynthesis	266:277	arg1	pathways					279:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life.
31563509	0	11	theme	polyprenol	154:163	arg1	substrates					175:184	polyprenol phosphate substrates	154:184	polyprenol phosphate substrates	154:184	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	10	12	theme	polyprenol	2032:2041	arg1	phosphates					2043:2052	polyprenol phosphates	2032:2052	polyprenol phosphates	2032:2052	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	5	13	theme	membrane-interaction	990:1009	arg1	domains					1011:1017	their membrane-interaction domains	984:1017	their membrane-interaction domains	984:1017	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	5	14	from	differences	969:979	arg1	domains					1011:1017	their membrane-interaction domains	984:1017	their membrane-interaction domains	984:1017	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	10	15	from	study	1984:1988	arg1	insights					1965:1972	The molecular insights	1951:1972	The molecular insights from this study	1951:1988	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	2	16	theme	amphiphilic	325:335	arg1	components					489:498	components	489:498	components of more complex substrates	489:525	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	16	theme	amphiphilic	325:335	arg1	substrates					365:374	substrates	365:374	substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases	365:479	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	16	theme	amphiphilic	325:335	arg1	molecules					337:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	5	17	theme	cis/trans	1082:1090	arg1	geometry					1092:1099	a unique cis/trans geometry	1073:1099	a unique cis/trans geometry in their polyprenol phosphate substrates	1073:1140	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	9	18	from	levels	1801:1806	arg1	phosphates					1762:1771	polyprenol phosphates	1751:1771	polyprenol phosphates at physiologically-relevant levels	1751:1806	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	8	19	theme	phosphate	1674:1682	arg1	recognition					1684:1694	polyprenol phosphate recognition	1663:1694	polyprenol phosphate recognition	1663:1694	Geometry is found to be important for binding to PglC; a conserved proline residue in the reentrant membrane helix is determined to drive polyprenol phosphate recognition and specificity.
31563509	4	20	theme	transferase	803:813	arg1	enzymes					815:821	monotopic phosphoglycosyl transferase enzymes	777:821	monotopic phosphoglycosyl transferase enzymes	777:821	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	0	21	with	interactions	136:147	arg1	substrates					175:184	polyprenol phosphate substrates	154:184	polyprenol phosphate substrates	154:184	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	5	22	theme	monotopic	1039:1047	arg1	enzymes					1049:1055	both polytopic and monotopic enzymes	1020:1055	both polytopic and monotopic enzymes	1020:1055	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	6	23	theme	multipronged	1164:1175	arg1	study					1205:1209	a multipronged biochemical and biophysical study	1162:1209	a multipronged biochemical and biophysical study of PglC	1162:1217	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	23	theme	multipronged	1164:1175	arg1	transferase					1248:1258	a monotopic phosphoglycosyl transferase	1220:1258	a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1220:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	0	24	theme	phosphoglycosyl	73:87	arg1	superfamily					101:111	the monotopic phosphoglycosyl transferase superfamily	59:111	the monotopic phosphoglycosyl transferase superfamily	59:111	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	0	25	from	Investigation	0:12	arg1	superfamily					101:111	the monotopic phosphoglycosyl transferase superfamily	59:111	the monotopic phosphoglycosyl transferase superfamily	59:111	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	7	26	theme	polyprenol	1401:1410	arg1	geometry					1422:1429	polyprenol phosphate geometry	1401:1429	polyprenol phosphate geometry	1401:1429	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	9	27	theme	Pyrene	1713:1718	arg1	studies					1733:1739	Pyrene fluorescence studies	1713:1739	Pyrene fluorescence studies	1713:1739	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	3	28	theme	double	570:575	arg1	geometry					582:589	double bond geometry	570:589	double bond geometry	570:589	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	4	29	theme	reentrant	908:916	arg1	helix					927:931	a single reentrant membrane helix	899:931	a single reentrant membrane helix	899:931	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	3	30	theme	linear	532:537	arg1	polyprenols					539:549	The linear polyprenols	528:549	The linear polyprenols	528:549	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	0	31	theme	key	122:124	arg1	interactions					136:147	key molecular interactions	122:147	key molecular interactions with polyprenol phosphate substrates	122:184	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	9	32	theme	physiologically-relevant	1776:1799	arg1	levels					1801:1806	physiologically-relevant levels	1776:1806	physiologically-relevant levels	1776:1806	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	6	33	theme	phosphoglycosyl	1232:1246	arg1	study					1205:1209	a multipronged biochemical and biophysical study	1162:1209	a multipronged biochemical and biophysical study of PglC	1162:1217	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	33	theme	phosphoglycosyl	1232:1246	arg1	transferase					1248:1258	a monotopic phosphoglycosyl transferase	1220:1258	a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1220:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	4	34	theme	polyprenol	863:872	arg1	substrates					884:893	polyprenol phosphate substrates	863:893	polyprenol phosphate substrates	863:893	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	2	35	theme	unique	318:323	arg1	components					489:498	components	489:498	components of more complex substrates	489:525	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	35	theme	unique	318:323	arg1	substrates					365:374	substrates	365:374	substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases	365:479	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	35	theme	unique	318:323	arg1	molecules					337:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	36	theme	substrates	516:525	arg1	components					489:498	components	489:498	components of more complex substrates	489:525	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	36	theme	substrates	516:525	arg1	molecules					337:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	5	37	theme	dramatic	960:967	arg1	differences					969:979	the dramatic differences	956:979	the dramatic differences in their membrane-interaction domains	956:1017	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	5	38	theme	polyprenol	1110:1119	arg1	substrates					1131:1140	their polyprenol phosphate substrates	1104:1140	their polyprenol phosphate substrates	1104:1140	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	10	39	from	proteins	2087:2094	arg1	biosynthesis					2114:2125	glycoconjugate biosynthesis	2099:2125	glycoconjugate biosynthesis	2099:2125	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	6	40	theme	PglC	1214:1217	arg1	study					1205:1209	a multipronged biochemical and biophysical study	1162:1209	a multipronged biochemical and biophysical study of PglC	1162:1217	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	40	theme	PglC	1214:1217	arg1	transferase					1248:1258	a monotopic phosphoglycosyl transferase	1220:1258	a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1220:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	8	41	theme	conserved	1582:1590	arg1	residue					1600:1606	a conserved proline residue	1580:1606	a conserved proline residue in the reentrant membrane helix	1580:1638	Geometry is found to be important for binding to PglC; a conserved proline residue in the reentrant membrane helix is determined to drive polyprenol phosphate recognition and specificity.
31563509	0	42	theme	reentrant	31:39	arg1	helix					50:54	the conserved reentrant membrane helix	17:54	the conserved reentrant membrane helix	17:54	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	7	43	theme	local	1497:1501	arg1	environment					1512:1522	the local membrane environment	1493:1522	the local membrane environment	1493:1522	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	9	44	with	phosphates	1905:1914	arg1	geometries					1939:1948	specific isoprene geometries	1921:1948	specific isoprene geometries	1921:1948	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	0	45	theme	helix	50:54	arg1	Investigation					0:12	Investigation	0:12	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily	0:111	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	9	46	theme	lipid	1843:1847	arg1	bilayer					1849:1855	the local lipid bilayer	1833:1855	the local lipid bilayer	1833:1855	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	10	47	theme	glycoconjugate	2099:2112	arg1	biosynthesis					2114:2125	glycoconjugate biosynthesis	2099:2125	glycoconjugate biosynthesis	2099:2125	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	3	48	theme	bond	577:580	arg1	geometry					582:589	double bond geometry	570:589	double bond geometry	570:589	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	6	49	theme	membrane-committed	1285:1302	arg1	step					1304:1307	the first membrane-committed step	1275:1307	the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1275:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	8	50	theme	membrane	1625:1632	arg1	helix					1634:1638	the reentrant membrane helix	1611:1638	the reentrant membrane helix	1611:1638	Geometry is found to be important for binding to PglC; a conserved proline residue in the reentrant membrane helix is determined to drive polyprenol phosphate recognition and specificity.
31563509	1	51	theme	life	306:309	arg1	life					306:309	life	306:309	life	306:309	Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life.
31563509	1	51	theme	life	306:309	arg1	domains					295:301	domains	295:301	domains of life	295:309	Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life.
31563509	10	52	theme	membrane-associated	2067:2085	arg1	proteins					2087:2094	diverse membrane-associated proteins	2059:2094	diverse membrane-associated proteins in glycoconjugate biosynthesis	2059:2125	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	7	53	theme	phosphate	1412:1420	arg1	geometry					1422:1429	polyprenol phosphate geometry	1401:1429	polyprenol phosphate geometry	1401:1429	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	10	54	theme	molecular	1955:1963	arg1	insights					1965:1972	The molecular insights	1951:1972	The molecular insights from this study	1951:1988	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	7	55	theme	substrate	1449:1457	arg1	binding					1459:1465	substrate binding	1449:1465	substrate binding to PglC	1449:1473	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	3	56	theme	membrane	647:654	arg1	proteins					656:663	polytopic membrane proteins	637:663	polytopic membrane proteins	637:663	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	9	57	theme	polyprenol	1894:1903	arg1	phosphates					1905:1914	polyprenol phosphates	1894:1914	polyprenol phosphates with specific isoprene geometries	1894:1948	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	4	58	theme	new	758:760	arg1	superfamily					762:772	a new superfamily	756:772	a new superfamily of monotopic phosphoglycosyl transferase enzymes	756:821	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	7	59	theme	geometry	1422:1429	arg1	significance					1385:1396	the significance	1381:1396	the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment	1381:1522	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	2	60	theme	membrane	389:396	arg1	proteins					398:405	polytopic membrane proteins	379:405	polytopic membrane proteins	379:405	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	60	theme	membrane	389:396	arg1	phosphoglycosyl					439:453	phosphoglycosyl	439:453	phosphoglycosyl	439:453	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	60	theme	membrane	389:396	arg1	transferases					468:479	glycosyl transferases	459:479	glycosyl transferases	459:479	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	6	61	gly	glycoprotein	1321:1332	arg1	glycoprotein					1321:1332	N-linked glycoprotein biosynthesis	1312:1345	N-linked glycoprotein biosynthesis in Campylobacter jejuni	1312:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	1	62	theme	glycoconjugate	251:264	arg1	pathways					279:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life.
31563509	3	63	theme	multiple	675:682	arg1	helices					698:704	multiple transmembrane helices	675:704	multiple transmembrane helices	675:704	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	9	64	theme	isoprene	1930:1937	arg1	geometries					1939:1948	specific isoprene geometries	1921:1948	specific isoprene geometries	1921:1948	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	6	65	theme	glycoprotein	1321:1332	arg1	biosynthesis					1334:1345	N-linked glycoprotein biosynthesis	1312:1345	N-linked glycoprotein biosynthesis in Campylobacter jejuni	1312:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	0	66	theme	phosphate	165:173	arg1	substrates					175:184	polyprenol phosphate substrates	154:184	polyprenol phosphate substrates	154:184	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	10	67	theme	phosphates	2043:2052	arg1	interactions					2016:2027	the interactions	2012:2027	the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis	2012:2125	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	5	68	theme	polytopic	1025:1033	arg1	enzymes					1049:1055	both polytopic and monotopic enzymes	1020:1055	both polytopic and monotopic enzymes	1020:1055	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	3	69	theme	transmembrane	684:696	arg1	helices					698:704	multiple transmembrane helices	675:704	multiple transmembrane helices	675:704	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	8	70	theme	polyprenol	1663:1672	arg1	recognition					1684:1694	polyprenol phosphate recognition	1663:1694	polyprenol phosphate recognition	1663:1694	Geometry is found to be important for binding to PglC; a conserved proline residue in the reentrant membrane helix is determined to drive polyprenol phosphate recognition and specificity.
31563509	5	71	theme	unique	1075:1080	arg1	geometry					1092:1099	a unique cis/trans geometry	1073:1099	a unique cis/trans geometry in their polyprenol phosphate substrates	1073:1140	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	6	72	theme	biophysical	1193:1203	arg1	study					1205:1209	a multipronged biochemical and biophysical study	1162:1209	a multipronged biochemical and biophysical study of PglC	1162:1217	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	72	theme	biophysical	1193:1203	arg1	transferase					1248:1258	a monotopic phosphoglycosyl transferase	1220:1258	a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1220:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	9	73	theme	polyprenol	1751:1760	arg1	phosphates					1762:1771	polyprenol phosphates	1751:1771	polyprenol phosphates at physiologically-relevant levels	1751:1806	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	0	74	theme	monotopic	63:71	arg1	superfamily					101:111	the monotopic phosphoglycosyl transferase superfamily	59:111	the monotopic phosphoglycosyl transferase superfamily	59:111	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	3	75	theme	rich	713:716	arg1	landscape					718:726	a rich landscape	711:726	a rich landscape for interactions	711:743	The linear polyprenols are constrained by double bond geometry and lend themselves well to interactions with polytopic membrane proteins, in which multiple transmembrane helices form a rich landscape for interactions.
31563509	9	76	theme	fluorescence	1720:1731	arg1	studies					1733:1739	Pyrene fluorescence studies	1713:1739	Pyrene fluorescence studies	1713:1739	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	6	77	theme	biochemical	1177:1187	arg1	study					1205:1209	a multipronged biochemical and biophysical study	1162:1209	a multipronged biochemical and biophysical study of PglC	1162:1217	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	77	theme	biochemical	1177:1187	arg1	transferase					1248:1258	a monotopic phosphoglycosyl transferase	1220:1258	a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1220:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	4	78	theme	phosphoglycosyl	787:801	arg1	enzymes					815:821	monotopic phosphoglycosyl transferase enzymes	777:821	monotopic phosphoglycosyl transferase enzymes	777:821	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	0	79	theme	transferase	89:99	arg1	superfamily					101:111	the monotopic phosphoglycosyl transferase superfamily	59:111	the monotopic phosphoglycosyl transferase superfamily	59:111	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	1	80	from	feature	220:226	arg1	pathways					279:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	membrane-associated glycoconjugate biosynthesis pathways	231:286	Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life.
31563509	1	81	theme	Long-chain	187:196	arg1	polyprenol					198:207	Long-chain polyprenol	187:207	Long-chain polyprenol	187:207	Long-chain polyprenol phosphates feature in membrane-associated glycoconjugate biosynthesis pathways across domains of life.
31563509	4	82	theme	enzymes	815:821	arg1	superfamily					762:772	a new superfamily	756:772	a new superfamily of monotopic phosphoglycosyl transferase enzymes	756:821	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	5	83	theme	phosphate	1121:1129	arg1	substrates					1131:1140	their polyprenol phosphate substrates	1104:1140	their polyprenol phosphate substrates	1104:1140	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	10	84	theme	diverse	2059:2065	arg1	proteins					2087:2094	diverse membrane-associated proteins	2059:2094	diverse membrane-associated proteins in glycoconjugate biosynthesis	2059:2125	The molecular insights from this study may shed new light on the interactions of polyprenol phosphates with diverse membrane-associated proteins in glycoconjugate biosynthesis.
31563509	0	85	theme	molecular	126:134	arg1	interactions					136:147	key molecular interactions	122:147	key molecular interactions with polyprenol phosphate substrates	122:184	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	4	86	theme	single	901:906	arg1	helix					927:931	a single reentrant membrane helix	899:931	a single reentrant membrane helix	899:931	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	6	87	theme	monotopic	1222:1230	arg1	study					1205:1209	a multipronged biochemical and biophysical study	1162:1209	a multipronged biochemical and biophysical study of PglC	1162:1217	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	87	theme	monotopic	1222:1230	arg1	transferase					1248:1258	a monotopic phosphoglycosyl transferase	1220:1258	a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1220:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	88	from	biosynthesis	1334:1345	arg1	jejuni					1364:1369	Campylobacter jejuni	1350:1369	Campylobacter jejuni	1350:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	0	89	theme	conserved	21:29	arg1	helix					50:54	the conserved reentrant membrane helix	17:54	the conserved reentrant membrane helix	17:54	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	7	90	theme	membrane	1503:1510	arg1	environment					1512:1522	the local membrane environment	1493:1522	the local membrane environment	1493:1522	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	4	91	theme	phosphate	874:882	arg1	substrates					884:893	polyprenol phosphate substrates	863:893	polyprenol phosphate substrates	863:893	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	2	92	theme	complex	508:514	arg1	substrates					516:525	more complex substrates	503:525	more complex substrates	503:525	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	0	93	theme	membrane	41:48	arg1	helix					50:54	the conserved reentrant membrane helix	17:54	the conserved reentrant membrane helix	17:54	Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates.
31563509	6	94	link	N-linked	1312:1319	arg1	biosynthesis					1334:1345	N-linked glycoprotein biosynthesis	1312:1345	N-linked glycoprotein biosynthesis in Campylobacter jejuni	1312:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	6	95	from	step	1304:1307	arg1	biosynthesis					1334:1345	N-linked glycoprotein biosynthesis	1312:1345	N-linked glycoprotein biosynthesis in Campylobacter jejuni	1312:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	9	96	theme	local	1837:1841	arg1	bilayer					1849:1855	the local lipid bilayer	1833:1855	the local lipid bilayer	1833:1855	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	6	97	theme	N-linked	1312:1319	arg1	biosynthesis					1334:1345	N-linked glycoprotein biosynthesis	1312:1345	N-linked glycoprotein biosynthesis in Campylobacter jejuni	1312:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	7	98	dep	significance	1385:1396	arg1	mediating					1439:1447	mediating	1439:1447	mediating substrate binding to PglC	1439:1473	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	7	98	dep	significance	1385:1396	arg1	modulating					1482:1491	modulating	1482:1491	modulating the local membrane environment	1482:1522	We probe the significance of polyprenol phosphate geometry both in mediating substrate binding to PglC and in modulating the local membrane environment.
31563509	8	99	theme	proline	1592:1598	arg1	residue					1600:1606	a conserved proline residue	1580:1606	a conserved proline residue in the reentrant membrane helix	1580:1638	Geometry is found to be important for binding to PglC; a conserved proline residue in the reentrant membrane helix is determined to drive polyprenol phosphate recognition and specificity.
31563509	9	100	theme	bilayer	1849:1855	arg1	disorder					1821:1828	the disorder	1817:1828	the disorder of the local lipid bilayer	1817:1855	Pyrene fluorescence studies show that polyprenol phosphates at physiologically-relevant levels increase the disorder of the local lipid bilayer; however, this effect is confined to polyprenol phosphates with specific isoprene geometries.
31563509	4	101	theme	membrane	918:925	arg1	helix					927:931	a single reentrant membrane helix	899:931	a single reentrant membrane helix	899:931	Recently, a new superfamily of monotopic phosphoglycosyl transferase enzymes has been identified that interacts with polyprenol phosphate substrates via a single reentrant membrane helix.
31563509	2	102	theme	proteins	398:405	arg1	substrates					365:374	substrates	365:374	substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases	365:479	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	2	102	theme	proteins	398:405	arg1	molecules					337:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules	312:345	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31563509	5	103	from	geometry	1092:1099	arg1	substrates					1131:1140	their polyprenol phosphate substrates	1104:1140	their polyprenol phosphate substrates	1104:1140	Intriguingly, despite the dramatic differences in their membrane-interaction domains, both polytopic and monotopic enzymes similarly favor a unique cis/trans geometry in their polyprenol phosphate substrates.
31563509	6	104	theme	first	1279:1283	arg1	step					1304:1307	the first membrane-committed step	1275:1307	the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni	1275:1369	Herein, we present a multipronged biochemical and biophysical study of PglC, a monotopic phosphoglycosyl transferase that catalyzes the first membrane-committed step in N-linked glycoprotein biosynthesis in Campylobacter jejuni.
31563509	8	105	theme	reentrant	1615:1623	arg1	helix					1634:1638	the reentrant membrane helix	1611:1638	the reentrant membrane helix	1611:1638	Geometry is found to be important for binding to PglC; a conserved proline residue in the reentrant membrane helix is determined to drive polyprenol phosphate recognition and specificity.
31563509	2	106	theme	glycosyl	459:466	arg1	transferases					468:479	glycosyl transferases	459:479	glycosyl transferases	459:479	These unique amphiphilic molecules are best known as substrates of polytopic membrane proteins, including polyprenol-phosphate phosphoglycosyl and glycosyl transferases, and as components of more complex substrates.
31527367	3	0	theme	deprivation	507:517	arg1	therapy					519:525	androgen deprivation therapy	498:525	androgen deprivation therapy	498:525	In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance.
31527367	4	1	theme	-like	630:634	arg1	differentiation					636:650	neuroendocrine (NE)-like differentiation	611:650	neuroendocrine (NE)-like differentiation of some prostate cancer cells	611:680	The androgen deprivation may trigger neuroendocrine (NE)-like differentiation of some prostate cancer cells.
31527367	1	2	theme	low	144:146	arg1	voltages					148:155	low voltages	144:155	low voltages	144:155	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	8	3	theme	mitogenic	1182:1190	arg1	factors					1192:1198	mitogenic factors	1182:1198	mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells	1182:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	8	4	theme	cells	1280:1284	arg1	proliferation					1235:1247	androgen-independent proliferation	1214:1247	androgen-independent proliferation of surrounding prostate cancer cells	1214:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	10	5	theme	clinical	1627:1634	arg1	evidence					1636:1643	clinical evidence	1627:1643	clinical evidence for diabetes-related poor prognosis of prostate cancer	1627:1698	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	8	6	theme	essential	1200:1208	arg1	factors					1192:1198	mitogenic factors	1182:1198	mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells	1182:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	6	7	theme	channel	953:959	arg1	activity					961:968	the channel activity	949:968	the channel activity of Cav3.2	949:978	NE-like LNCaP cells overexpress Cav3.2 through the CREB/Egr-1 pathway and also cystathionine-γ-lyase (CSE), which generates H2S that enhances the channel activity of Cav3.2.
31527367	11	8	theme	cancer	1824:1829	arg1	pathophysiology					1796:1810	the pathophysiology	1792:1810	the pathophysiology of prostate cancer	1792:1829	Thus, Cav3.2 is considered to play a role in the pathophysiology of prostate cancer, and may serve as a therapeutic target.
31527367	7	9	theme	Cav3.2	1061:1066	arg1	activity					1037:1044	the activity	1033:1044	the activity of upregulated Cav3.2	1033:1066	H2S generated by upregulated CSE appears to enhance the activity of upregulated Cav3.2 after the differentiation.
31527367	1	10	theme	neuronal	167:174	arg1	release					219:225	spontaneous neurotransmitter release	190:225	spontaneous neurotransmitter release	190:225	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	1	10	theme	neuronal	167:174	arg1	secretion					236:244	hormone secretion	228:244	hormone secretion	228:244	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	1	10	theme	neuronal	167:174	arg1	excitability					176:187	neuronal excitability	167:187	neuronal excitability	167:187	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	1	10	theme	neuronal	167:174	arg1	etc.					247:250	etc.	247:250	etc.	247:250	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	8	11	theme	androgen-independent	1214:1233	arg1	proliferation					1235:1247	androgen-independent proliferation	1214:1247	androgen-independent proliferation of surrounding prostate cancer cells	1214:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	10	12	theme	poor	1666:1669	arg1	prognosis					1671:1679	diabetes-related poor prognosis	1649:1679	diabetes-related poor prognosis of prostate cancer	1649:1698	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	7	13	theme	upregulated	998:1008	arg1	CSE					1010:1012	upregulated CSE	998:1012	upregulated CSE	998:1012	H2S generated by upregulated CSE appears to enhance the activity of upregulated Cav3.2 after the differentiation.
31527367	3	14	theme	hormone-therapy	546:560	arg1	resistance					562:571	hormone-therapy resistance	546:571	hormone-therapy resistance	546:571	In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance.
31527367	1	15	theme	T-type	99:104	arg1	channels					111:118	T-type Ca2+ channels	99:118	T-type Ca2+ channels	99:118	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	4	16	theme	prostate	660:667	arg1	cells					676:680	some prostate cancer cells	655:680	some prostate cancer cells	655:680	The androgen deprivation may trigger neuroendocrine (NE)-like differentiation of some prostate cancer cells.
31527367	0	17	theme	cancer	49:54	arg1	cells					56:60	prostate cancer cells	40:60	prostate cancer cells	40:60	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells].
31527367	1	18	theme	cells	309:313	arg1	proliferation					276:288	proliferation	276:288	proliferation of distinct cancer cells	276:313	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	5	19	theme	cancer	756:761	arg1	cells					769:773	human prostate cancer LNCaP cells	741:773	human prostate cancer LNCaP cells	741:773	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	4	20	theme	cells	676:680	arg1	differentiation					636:650	neuroendocrine (NE)-like differentiation	611:650	neuroendocrine (NE)-like differentiation of some prostate cancer cells	611:680	The androgen deprivation may trigger neuroendocrine (NE)-like differentiation of some prostate cancer cells.
31527367	5	21	theme	human	741:745	arg1	cells					769:773	human prostate cancer LNCaP cells	741:773	human prostate cancer LNCaP cells	741:773	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	9	22	theme	extracellular	1314:1326	arg1	levels					1336:1341	increased extracellular glucose levels	1304:1341	increased extracellular glucose levels	1304:1341	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	0	23	from	[Role	0:4	arg1	cells					56:60	prostate cancer cells	40:60	prostate cancer cells	40:60	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells].
31527367	9	24	theme	Cav3.2	1351:1356	arg1	activity					1358:1365	Cav3.2 activity	1351:1365	Cav3.2 activity	1351:1365	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	0	25	theme	channels	28:35	arg1	[Role					0:4	[Role	0:4	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells	0:60	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells].
31527367	2	26	from	patients	430:437	arg1	samples					401:407	biopsy samples	394:407	biopsy samples from prostate cancer patients	394:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	2	26	from	patients	430:437	arg1	%					389:389	100%	386:389	100% of biopsy samples from prostate cancer patients	386:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	10	27	theme	high	1488:1491	arg1	glucose					1493:1499	high glucose	1488:1499	high glucose	1488:1499	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	10	28	theme	prostate	1684:1691	arg1	cancer					1693:1698	prostate cancer	1684:1698	prostate cancer	1684:1698	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	5	29	theme	NE-like	782:788	arg1	differentiation					790:804	NE-like differentiation	782:804	NE-like differentiation	782:804	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	1	30	theme	voltage-gated	70:82	arg1	channels					89:96	voltage-gated Ca2+ channels	70:96	voltage-gated Ca2+ channels	70:96	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	2	31	theme	biopsy	394:399	arg1	samples					401:407	biopsy samples	394:407	biopsy samples from prostate cancer patients	394:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	10	32	theme	therapy	1727:1733	arg1	resistance					1735:1744	hormone therapy resistance	1719:1744	hormone therapy resistance	1719:1744	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	0	33	theme	Cav3.2	9:14	arg1	channels					28:35	Cav3.2 T-type Ca2+ channels	9:35	Cav3.2 T-type Ca2+ channels	9:35	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells].
31527367	6	34	theme	CREB/Egr-1	858:867	arg1	pathway					869:875	the CREB/Egr-1 pathway	854:875	the CREB/Egr-1 pathway	854:875	NE-like LNCaP cells overexpress Cav3.2 through the CREB/Egr-1 pathway and also cystathionine-γ-lyase (CSE), which generates H2S that enhances the channel activity of Cav3.2.
31527367	10	35	theme	enhanced	1517:1524	arg1	function					1534:1541	enhanced channel function	1517:1541	enhanced channel function	1517:1541	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	8	36	theme	prostate	1264:1271	arg1	cells					1280:1284	surrounding prostate cancer cells	1252:1284	surrounding prostate cancer cells	1252:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	0	37	theme	Ca2+	23:26	arg1	channels					28:35	Cav3.2 T-type Ca2+ channels	9:35	Cav3.2 T-type Ca2+ channels	9:35	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells].
31527367	2	38	theme	cancer	423:428	arg1	patients					430:437	prostate cancer patients	414:437	prostate cancer patients	414:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	10	39	theme	Cav3.2	1565:1570	arg1	overexpression					1547:1560	overexpression	1547:1560	overexpression of Cav3.2	1547:1570	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	10	39	theme	Cav3.2	1565:1570	arg1	function					1534:1541	enhanced channel function	1517:1541	enhanced channel function	1517:1541	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	5	40	theme	Cav3.2	731:736	arg1	function					719:726	function	719:726	function	719:726	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	5	40	theme	Cav3.2	731:736	arg1	expression					704:713	expression	704:713	expression	704:713	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	1	41	theme	distinct	293:300	arg1	cells					309:313	distinct cancer cells	293:313	distinct cancer cells	293:313	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	9	42	theme	Cav3.2	1414:1419	arg1	glycosylation					1397:1409	asparagine (N)-linked glycosylation	1375:1409	asparagine (N)-linked glycosylation	1375:1409	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	8	43	theme	Cav3.2	1108:1113	arg1	activity					1115:1122	The enhanced Cav3.2 activity	1095:1122	The enhanced Cav3.2 activity in NE-like cells	1095:1139	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	6	44	theme	LNCaP	815:819	arg1	cells					821:825	NE-like LNCaP cells	807:825	NE-like LNCaP cells	807:825	NE-like LNCaP cells overexpress Cav3.2 through the CREB/Egr-1 pathway and also cystathionine-γ-lyase (CSE), which generates H2S that enhances the channel activity of Cav3.2.
31527367	2	45	theme	Ca2+	347:350	arg1	channels					352:359	T-type Ca2+ channels	340:359	T-type Ca2+ channels	340:359	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	0	46	theme	prostate	40:47	arg1	cells					56:60	prostate cancer cells	40:60	prostate cancer cells	40:60	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells].
31527367	2	47	from	%	389:389	arg1	patients					430:437	prostate cancer patients	414:437	prostate cancer patients	414:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	2	47	from	%	389:389	arg1	detectable					372:381	detectable	372:381	detectable	372:381	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	10	48	theme	NE-like	1575:1581	arg1	cells					1589:1593	NE-like LNCaP cells	1575:1593	NE-like LNCaP cells	1575:1593	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	3	49	theme	cancer	461:466	arg1	cells					468:472	prostate cancer cells	452:472	prostate cancer cells	452:472	In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance.
31527367	1	50	theme	hormone	228:234	arg1	secretion					236:244	hormone secretion	228:244	hormone secretion	228:244	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	1	50	theme	hormone	228:234	arg1	excitability					176:187	neuronal excitability	167:187	neuronal excitability	167:187	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	3	51	theme	androgen	498:505	arg1	therapy					519:525	androgen deprivation therapy	498:525	androgen deprivation therapy	498:525	In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance.
31527367	9	52	theme	diabetic	1448:1455	arg1	neuropathy					1457:1466	diabetic neuropathy	1448:1466	diabetic neuropathy	1448:1466	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	8	53	theme	increased	1159:1167	arg1	secretion					1169:1177	increased secretion	1159:1177	increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells	1159:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	10	54	from	overexpression	1547:1560	arg1	cells					1589:1593	NE-like LNCaP cells	1575:1593	NE-like LNCaP cells	1575:1593	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	8	55	theme	surrounding	1252:1262	arg1	cells					1280:1284	surrounding prostate cancer cells	1252:1284	surrounding prostate cancer cells	1252:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	3	56	from	general	443:449	arg1	sensitive					485:493	sensitive	485:493	sensitive	485:493	In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance.
31527367	8	57	theme	cancer	1273:1278	arg1	cells					1280:1284	surrounding prostate cancer cells	1252:1284	surrounding prostate cancer cells	1252:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	7	58	theme	upregulated	1049:1059	arg1	Cav3.2					1061:1066	upregulated Cav3.2	1049:1066	upregulated Cav3.2	1049:1066	H2S generated by upregulated CSE appears to enhance the activity of upregulated Cav3.2 after the differentiation.
31527367	8	59	theme	factors	1192:1198	arg1	secretion					1169:1177	increased secretion	1159:1177	increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells	1159:1284	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	5	60	from	function	719:726	arg1	cells					769:773	human prostate cancer LNCaP cells	741:773	human prostate cancer LNCaP cells	741:773	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	10	61	theme	diabetes-related	1649:1664	arg1	prognosis					1671:1679	diabetes-related poor prognosis	1649:1679	diabetes-related poor prognosis of prostate cancer	1649:1698	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	11	62	theme	therapeutic	1851:1861	arg1	target					1863:1868	a therapeutic target	1849:1868	a therapeutic target	1849:1868	Thus, Cav3.2 is considered to play a role in the pathophysiology of prostate cancer, and may serve as a therapeutic target.
31527367	11	62	theme	therapeutic	1851:1861	arg1	Cav3.2					1753:1758	Cav3.2	1753:1758	Cav3.2	1753:1758	Thus, Cav3.2 is considered to play a role in the pathophysiology of prostate cancer, and may serve as a therapeutic target.
31527367	5	63	from	expression	704:713	arg1	cells					769:773	human prostate cancer LNCaP cells	741:773	human prostate cancer LNCaP cells	741:773	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	1	64	theme	Ca2+	106:109	arg1	channels					111:118	T-type Ca2+ channels	99:118	T-type Ca2+ channels	99:118	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	5	65	dep	expression	704:713	arg1	the					700:702	the	700:702	the	700:702	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	10	66	from	function	1534:1541	arg1	cells					1589:1593	NE-like LNCaP cells	1575:1593	NE-like LNCaP cells	1575:1593	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	1	67	theme	spontaneous	190:200	arg1	release					219:225	spontaneous neurotransmitter release	190:225	spontaneous neurotransmitter release	190:225	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	1	67	theme	spontaneous	190:200	arg1	excitability					176:187	neuronal excitability	167:187	neuronal excitability	167:187	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	3	68	from	sensitive	485:493	arg1	general					443:449	general	443:449	general	443:449	In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance.
31527367	9	69	theme	increased	1304:1312	arg1	levels					1336:1341	increased extracellular glucose levels	1304:1341	increased extracellular glucose levels	1304:1341	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	8	70	from	activity	1115:1122	arg1	cells					1135:1139	NE-like cells	1127:1139	NE-like cells	1127:1139	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	4	71	theme	cancer	669:674	arg1	cells					676:680	some prostate cancer cells	655:680	some prostate cancer cells	655:680	The androgen deprivation may trigger neuroendocrine (NE)-like differentiation of some prostate cancer cells.
31527367	11	72	theme	prostate	1815:1822	arg1	cancer					1824:1829	prostate cancer	1815:1829	prostate cancer	1815:1829	Thus, Cav3.2 is considered to play a role in the pathophysiology of prostate cancer, and may serve as a therapeutic target.
31527367	9	73	theme	glucose	1328:1334	arg1	levels					1336:1341	increased extracellular glucose levels	1304:1341	increased extracellular glucose levels	1304:1341	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	6	74	theme	Cav3.2	973:978	arg1	activity					961:968	the channel activity	949:968	the channel activity of Cav3.2	949:978	NE-like LNCaP cells overexpress Cav3.2 through the CREB/Egr-1 pathway and also cystathionine-γ-lyase (CSE), which generates H2S that enhances the channel activity of Cav3.2.
31527367	10	75	dep	function	1534:1541	arg1	the					1513:1515	the	1513:1515	the	1513:1515	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	10	76	theme	cancer	1693:1698	arg1	prognosis					1671:1679	diabetes-related poor prognosis	1649:1679	diabetes-related poor prognosis of prostate cancer	1649:1698	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	2	77	theme	samples	401:407	arg1	samples					401:407	biopsy samples	394:407	biopsy samples from prostate cancer patients	394:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	2	77	theme	samples	401:407	arg1	%					389:389	100%	386:389	100% of biopsy samples from prostate cancer patients	386:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	2	78	theme	channels	352:359	arg1	isoforms					328:335	three isoforms	322:335	three isoforms of T-type Ca2+ channels	322:359	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	0	79	theme	T-type	16:21	arg1	channels					28:35	Cav3.2 T-type Ca2+ channels	9:35	Cav3.2 T-type Ca2+ channels	9:35	[Role of Cav3.2 T-type Ca2+ channels in prostate cancer cells].
31527367	1	80	theme	Ca2+	84:87	arg1	channels					89:96	voltage-gated Ca2+ channels	70:96	voltage-gated Ca2+ channels	70:96	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	10	81	theme	channel	1526:1532	arg1	function					1534:1541	enhanced channel function	1517:1541	enhanced channel function	1517:1541	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	9	82	gly	glycosylation	1397:1409	arg1	Cav3.2					1414:1419	Cav3.2	1414:1419	Cav3.2	1414:1419	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	10	83	theme	hormone	1719:1725	arg1	resistance					1735:1744	hormone therapy resistance	1719:1744	hormone therapy resistance	1719:1744	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	5	84	theme	prostate	747:754	arg1	cells					769:773	human prostate cancer LNCaP cells	741:773	human prostate cancer LNCaP cells	741:773	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	5	85	theme	LNCaP	763:767	arg1	cells					769:773	human prostate cancer LNCaP cells	741:773	human prostate cancer LNCaP cells	741:773	We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation.
31527367	9	86	theme	-linked	1389:1395	arg1	glycosylation					1397:1409	asparagine (N)-linked glycosylation	1375:1409	asparagine (N)-linked glycosylation	1375:1409	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	8	87	theme	enhanced	1099:1106	arg1	activity					1115:1122	The enhanced Cav3.2 activity	1095:1122	The enhanced Cav3.2 activity in NE-like cells	1095:1139	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	2	88	theme	prostate	414:421	arg1	patients					430:437	prostate cancer patients	414:437	prostate cancer patients	414:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	3	89	theme	prostate	452:459	arg1	cells					468:472	prostate cancer cells	452:472	prostate cancer cells	452:472	In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance.
31527367	1	90	theme	cancer	302:307	arg1	cells					309:313	distinct cancer cells	293:313	distinct cancer cells	293:313	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	9	91	link	-linked	1389:1395	arg1	glycosylation					1397:1409	asparagine (N)-linked glycosylation	1375:1409	asparagine (N)-linked glycosylation	1375:1409	It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy.
31527367	4	92	theme	androgen	578:585	arg1	deprivation					587:597	The androgen deprivation	574:597	The androgen deprivation	574:597	The androgen deprivation may trigger neuroendocrine (NE)-like differentiation of some prostate cancer cells.
31527367	10	93	theme	resistance	1735:1744	arg1	evidence					1636:1643	clinical evidence	1627:1643	clinical evidence for diabetes-related poor prognosis of prostate cancer	1627:1698	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	10	93	theme	resistance	1735:1744	arg1	development					1704:1714	development	1704:1714	development of hormone therapy resistance	1704:1744	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	1	94	theme	neurotransmitter	202:217	arg1	release					219:225	spontaneous neurotransmitter release	190:225	spontaneous neurotransmitter release	190:225	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	1	94	theme	neurotransmitter	202:217	arg1	excitability					176:187	neuronal excitability	167:187	neuronal excitability	167:187	Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells.
31527367	8	95	theme	NE-like	1127:1133	arg1	cells					1135:1139	NE-like cells	1127:1139	NE-like cells	1127:1139	The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells.
31527367	6	96	theme	NE-like	807:813	arg1	cells					821:825	NE-like LNCaP cells	807:825	NE-like LNCaP cells	807:825	NE-like LNCaP cells overexpress Cav3.2 through the CREB/Egr-1 pathway and also cystathionine-γ-lyase (CSE), which generates H2S that enhances the channel activity of Cav3.2.
31527367	2	97	from	detectable	372:381	arg1	samples					401:407	biopsy samples	394:407	biopsy samples from prostate cancer patients	394:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	2	97	from	detectable	372:381	arg1	%					389:389	100%	386:389	100% of biopsy samples from prostate cancer patients	386:437	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31527367	10	98	theme	LNCaP	1583:1587	arg1	cells					1589:1593	NE-like LNCaP cells	1575:1593	NE-like LNCaP cells	1575:1593	We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance.
31527367	2	99	theme	T-type	340:345	arg1	channels					352:359	T-type Ca2+ channels	340:359	T-type Ca2+ channels	340:359	Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients.
31907993	6	0	theme	galactosylated	1002:1015	arg1	N-glycans					1017:1025	biantennary galactosylated N-glycans	990:1025	biantennary galactosylated N-glycans	990:1025	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	5	1	theme	glycosylation-dependent	701:723	arg1	regulation					725:734	glycosylation-dependent regulation	701:734	glycosylation-dependent regulation of CD11b/CD18 function	701:757	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	2	2	theme	inflammatory	354:365	arg1	conditions					367:376	numerous inflammatory conditions	345:376	numerous inflammatory conditions including inflammatory bowel disease	345:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	2	theme	inflammatory	354:365	arg1	disease					407:413	inflammatory bowel disease	388:413	inflammatory bowel disease	388:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	8	3	from	manipulation	1522:1533	arg1	diseases					1623:1630	chronic inflammatory diseases	1602:1630	chronic inflammatory diseases	1602:1630	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	4	4	link	N-linked	605:612	arg1	X					627:627	the N-linked glycan Lewis X	601:627	the N-linked glycan Lewis X	601:627	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	4	5	theme	PMN	645:647	arg1	migration					665:673	PMN transepithelial migration	645:673	PMN transepithelial migration (TEpM)	645:680	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	4	5	theme	PMN	645:647	arg1	TEpM					676:679	TEpM	676:679	TEpM	676:679	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	6	6	theme	glycan	863:868	arg1	epitopes					870:877	Unusual glycan epitopes	855:877	Unusual glycan epitopes identified on CD11b/CD18	855:902	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	2	7	theme	associated	279:288	arg1	damage					308:313	associated epithelial tissue damage	279:313	associated epithelial tissue damage	279:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	6	8	theme	Nivalis	971:977	arg1	lectin					979:984	the Galanthus Nivalis lectin	957:984	the Galanthus Nivalis lectin	957:984	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	2	9	theme	PMNs	270:273	arg1	trafficking					255:265	dysregulated mucosal trafficking	234:265	dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage	234:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	9	theme	PMNs	270:273	arg1	hallmark					333:340	a pathological hallmark	318:340	a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease	318:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	7	10	theme	intracellular	1193:1205	arg1	events					1217:1222	altered intracellular signaling events	1185:1222	altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis	1185:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	1	11	theme	innate	179:184	arg1	response					193:200	the innate immune response	175:200	the innate immune response to invading pathogens	175:222	Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens.
31907993	8	12	theme	discrete	1401:1408	arg1	motifs					1417:1422	discrete glycan motifs	1401:1422	discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose	1401:1476	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	5	13	theme	MALDI	773:777	arg1	MS					802:803	MS	802:803	MS	802:803	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	5	13	theme	MALDI	773:777	arg1	Spectrometry					788:799	MALDI TOF Mass Spectrometry	773:799	MALDI TOF Mass Spectrometry (MS) analyses	773:813	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	2	14	theme	tissue	301:306	arg1	damage					308:313	associated epithelial tissue damage	279:313	associated epithelial tissue damage	279:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	6	15	theme	Vulgaris	1055:1062	arg1	erythroagglutinin					1064:1080	the Phaseolus Vulgaris erythroagglutinin	1041:1080	the Phaseolus Vulgaris erythroagglutinin lectin	1041:1087	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	8	16	theme	chronic	1602:1608	arg1	diseases					1623:1630	chronic inflammatory diseases	1602:1630	chronic inflammatory diseases	1602:1630	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	7	17	from	targeting	1126:1134	arg1	CD11b					1150:1154	CD11b	1150:1154	CD11b with such lectins	1150:1172	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	5	18	theme	Mass	783:786	arg1	MS					802:803	MS	802:803	MS	802:803	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	5	18	theme	Mass	783:786	arg1	Spectrometry					788:799	MALDI TOF Mass Spectrometry	773:799	MALDI TOF Mass Spectrometry (MS) analyses	773:813	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	7	19	theme	inflammatory	1276:1287	arg1	release					1334:1340	superoxide release	1323:1340	superoxide release	1323:1340	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	19	theme	inflammatory	1276:1287	arg1	functions					1289:1297	key PMN inflammatory functions	1268:1297	key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis	1268:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	19	theme	inflammatory	1276:1287	arg1	apoptosis					1346:1354	apoptosis	1346:1354	apoptosis	1346:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	19	theme	inflammatory	1276:1287	arg1	phagocytosis					1309:1320	phagocytosis	1309:1320	phagocytosis	1309:1320	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	1	20	theme	invading	205:212	arg1	pathogens					214:222	invading pathogens	205:222	invading pathogens	205:222	Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens.
31907993	5	21	theme	function	750:757	arg1	regulation					725:734	glycosylation-dependent regulation	701:734	glycosylation-dependent regulation of CD11b/CD18 function	701:757	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	8	22	theme	biantennary	1456:1466	arg1	galactose					1468:1476	biantennary galactose	1456:1476	biantennary galactose	1456:1476	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	0	23	theme	glycan	60:65	arg1	epitopes					67:74	glycan epitopes	60:74	glycan epitopes	60:74	Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18.
31907993	2	24	theme	dysregulated	234:245	arg1	trafficking					255:265	dysregulated mucosal trafficking	234:265	dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage	234:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	24	theme	dysregulated	234:245	arg1	hallmark					333:340	a pathological hallmark	318:340	a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease	318:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	4	25	theme	Previous	548:555	arg1	studies					557:563	Previous studies	548:563	Previous studies	548:563	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	1	26	theme	critical	158:165	arg1	role					167:170	a critical role	156:170	a critical role	156:170	Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens.
31907993	8	27	theme	novel	1494:1498	arg1	targets					1500:1506	novel targets	1494:1506	novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases	1494:1630	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	3	28	gly	glycoprotein	420:431	arg1	glycoprotein					420:431	The glycoprotein CD11b/CD18	416:442	The glycoprotein CD11b/CD18	416:442	The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions.
31907993	7	29	theme	superoxide	1323:1332	arg1	release					1334:1340	superoxide release	1323:1340	superoxide release	1323:1340	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	0	30	theme	selective	37:45	arg1	targeting					47:55	selective targeting	37:55	selective targeting of glycan epitopes	37:74	Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18.
31907993	3	31	theme	well-described	452:465	arg1	role					467:470	a well-described role	450:470	a well-described role	450:470	The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions.
31907993	4	32	theme	N-linked	605:612	arg1	X					627:627	the N-linked glycan Lewis X	601:627	the N-linked glycan Lewis X	601:627	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	8	33	theme	CD11b	1538:1542	arg1	function					1544:1551	CD11b function	1538:1551	CD11b function	1538:1551	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	0	34	theme	neutrophil	14:23	arg1	function					25:32	neutrophil function	14:32	neutrophil function	14:32	Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18.
31907993	4	35	theme	Lewis	621:625	arg1	X					627:627	the N-linked glycan Lewis X	601:627	the N-linked glycan Lewis X	601:627	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	3	36	theme	PMN	486:488	arg1	migration					506:514	PMN transepithelial migration	486:514	PMN transepithelial migration	486:514	The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions.
31907993	7	37	theme	PMN	1272:1274	arg1	release					1334:1340	superoxide release	1323:1340	superoxide release	1323:1340	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	37	theme	PMN	1272:1274	arg1	functions					1289:1297	key PMN inflammatory functions	1268:1297	key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis	1268:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	37	theme	PMN	1272:1274	arg1	apoptosis					1346:1354	apoptosis	1346:1354	apoptosis	1346:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	37	theme	PMN	1272:1274	arg1	phagocytosis					1309:1320	phagocytosis	1309:1320	phagocytosis	1309:1320	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	5	38	theme	human	843:847	arg1	PMNs					849:852	human PMNs	843:852	human PMNs	843:852	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	3	39	theme	glycoprotein	420:431	arg1	CD11b/CD18					433:442	The glycoprotein CD11b/CD18	416:442	The glycoprotein CD11b/CD18	416:442	The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions.
31907993	2	40	theme	numerous	345:352	arg1	conditions					367:376	numerous inflammatory conditions	345:376	numerous inflammatory conditions including inflammatory bowel disease	345:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	40	theme	numerous	345:352	arg1	disease					407:413	inflammatory bowel disease	388:413	inflammatory bowel disease	388:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	6	41	theme	high	913:916	arg1	oligosaccharides					926:941	high Mannose oligosaccharides	913:941	high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin	913:984	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	8	42	theme	tissue	1585:1590	arg1	damage					1592:1597	PMN-associated tissue damage	1570:1597	PMN-associated tissue damage	1570:1597	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	3	43	theme	PMN	520:522	arg1	functions					537:545	PMN inflammatory functions	520:545	PMN inflammatory functions	520:545	The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions.
31907993	4	44	theme	transepithelial	649:663	arg1	migration					665:673	PMN transepithelial migration	645:673	PMN transepithelial migration (TEpM)	645:680	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	4	44	theme	transepithelial	649:663	arg1	TEpM					676:679	TEpM	676:679	TEpM	676:679	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	2	45	theme	inflammatory	388:399	arg1	disease					407:413	inflammatory bowel disease	388:413	inflammatory bowel disease	388:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	46	theme	conditions	367:376	arg1	trafficking					255:265	dysregulated mucosal trafficking	234:265	dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage	234:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	46	theme	conditions	367:376	arg1	hallmark					333:340	a pathological hallmark	318:340	a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease	318:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	6	47	theme	biantennary	990:1000	arg1	N-glycans					1017:1025	biantennary galactosylated N-glycans	990:1025	biantennary galactosylated N-glycans	990:1025	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	5	48	theme	regulation	725:734	arg1	evidence					689:696	evidence	689:696	evidence of glycosylation-dependent regulation of CD11b/CD18 function	689:757	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	2	49	theme	epithelial	290:299	arg1	damage					308:313	associated epithelial tissue damage	279:313	associated epithelial tissue damage	279:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	7	50	theme	signaling	1207:1215	arg1	events					1217:1222	altered intracellular signaling events	1185:1222	altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis	1185:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	6	51	theme	Unusual	855:861	arg1	epitopes					870:877	Unusual glycan epitopes	855:877	Unusual glycan epitopes identified on CD11b/CD18	855:902	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	8	52	from	reduction	1557:1565	arg1	diseases					1623:1630	chronic inflammatory diseases	1602:1630	chronic inflammatory diseases	1602:1630	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	6	53	theme	Galanthus	961:969	arg1	lectin					979:984	the Galanthus Nivalis lectin	957:984	the Galanthus Nivalis lectin	957:984	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	7	54	theme	altered	1185:1191	arg1	events					1217:1222	altered intracellular signaling events	1185:1222	altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis	1185:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	2	55	theme	damage	308:313	arg1	trafficking					255:265	dysregulated mucosal trafficking	234:265	dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage	234:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	55	theme	damage	308:313	arg1	hallmark					333:340	a pathological hallmark	318:340	a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease	318:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	1	56	theme	immune	186:191	arg1	response					193:200	the innate immune response	175:200	the innate immune response to invading pathogens	175:222	Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens.
31907993	6	57	theme	erythroagglutinin	1064:1080	arg1	lectin					1082:1087	the Phaseolus Vulgaris erythroagglutinin lectin	1041:1087	the Phaseolus Vulgaris erythroagglutinin lectin	1041:1087	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	8	58	theme	inflammatory	1610:1621	arg1	diseases					1623:1630	chronic inflammatory diseases	1602:1630	chronic inflammatory diseases	1602:1630	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	7	59	theme	such	1161:1164	arg1	lectins					1166:1172	such lectins	1161:1172	such lectins	1161:1172	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	6	60	theme	Phaseolus	1045:1053	arg1	erythroagglutinin					1064:1080	the Phaseolus Vulgaris erythroagglutinin	1041:1080	the Phaseolus Vulgaris erythroagglutinin lectin	1041:1087	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	8	61	theme	glycan	1410:1415	arg1	motifs					1417:1422	discrete glycan motifs	1401:1422	discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose	1401:1476	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	5	62	theme	Spectrometry	788:799	arg1	analyses					806:813	MALDI TOF Mass Spectrometry (MS) analyses	773:813	MALDI TOF Mass Spectrometry (MS) analyses	773:813	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	5	63	theme	CD11b/CD18	739:748	arg1	function					750:757	CD11b/CD18 function	739:757	CD11b/CD18 function	739:757	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	1	64	theme	Polymorphonuclear	114:130	arg1	PMNs					145:148	PMNs	145:148	PMNs	145:148	Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens.
31907993	1	64	theme	Polymorphonuclear	114:130	arg1	neutrophils					132:142	Polymorphonuclear neutrophils	114:142	Polymorphonuclear neutrophils (PMNs)	114:149	Polymorphonuclear neutrophils (PMNs) play a critical role in the innate immune response to invading pathogens.
31907993	7	65	theme	glycans	1139:1145	arg1	targeting					1126:1134	selective targeting	1116:1134	selective targeting of glycans on CD11b with such lectins	1116:1172	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	66	theme	selective	1116:1124	arg1	targeting					1126:1134	selective targeting	1116:1134	selective targeting of glycans on CD11b with such lectins	1116:1172	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	0	67	theme	epitopes	67:74	arg1	targeting					47:55	selective targeting	37:55	selective targeting of glycan epitopes	37:74	Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18.
31907993	2	68	theme	mucosal	247:253	arg1	trafficking					255:265	dysregulated mucosal trafficking	234:265	dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage	234:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	68	theme	mucosal	247:253	arg1	hallmark					333:340	a pathological hallmark	318:340	a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease	318:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	0	69	theme	integrin	93:100	arg1	CD11b/CD18					102:111	the integrin CD11b/CD18	89:111	the integrin CD11b/CD18	89:111	Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18.
31907993	2	70	theme	pathological	320:331	arg1	trafficking					255:265	dysregulated mucosal trafficking	234:265	dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage	234:313	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	2	70	theme	pathological	320:331	arg1	hallmark					333:340	a pathological hallmark	318:340	a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease	318:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	7	71	with	CD11b	1150:1154	arg1	lectins					1166:1172	such lectins	1161:1172	such lectins	1161:1172	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	5	72	theme	TOF	779:781	arg1	MS					802:803	MS	802:803	MS	802:803	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	5	72	theme	TOF	779:781	arg1	Spectrometry					788:799	MALDI TOF Mass Spectrometry	773:799	MALDI TOF Mass Spectrometry (MS) analyses	773:813	Given evidence of glycosylation-dependent regulation of CD11b/CD18 function, we performed MALDI TOF Mass Spectrometry (MS) analyses on CD11b/CD18 purified from human PMNs.
31907993	4	73	theme	glycan	614:619	arg1	X					627:627	the N-linked glycan Lewis X	601:627	the N-linked glycan Lewis X	601:627	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	8	74	theme	selective	1512:1520	arg1	manipulation					1522:1533	selective manipulation	1512:1533	selective manipulation of CD11b function	1512:1551	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	2	75	theme	bowel	401:405	arg1	disease					407:413	inflammatory bowel disease	388:413	inflammatory bowel disease	388:413	However, dysregulated mucosal trafficking of PMNs and associated epithelial tissue damage is a pathological hallmark of numerous inflammatory conditions including inflammatory bowel disease.
31907993	0	76	theme	function	25:32	arg1	Regulation					0:9	Regulation	0:9	Regulation of neutrophil function by selective targeting of glycan epitopes	0:74	Regulation of neutrophil function by selective targeting of glycan epitopes expressed on the integrin CD11b/CD18.
31907993	4	77	theme	X	627:627	arg1	targeting					588:596	targeting	588:596	targeting of the N-linked glycan Lewis X on CD11b	588:636	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	7	78	theme	key	1268:1270	arg1	release					1334:1340	superoxide release	1323:1340	superoxide release	1323:1340	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	78	theme	key	1268:1270	arg1	functions					1289:1297	key PMN inflammatory functions	1268:1297	key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis	1268:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	78	theme	key	1268:1270	arg1	apoptosis					1346:1354	apoptosis	1346:1354	apoptosis	1346:1354	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	7	78	theme	key	1268:1270	arg1	phagocytosis					1309:1320	phagocytosis	1309:1320	phagocytosis	1309:1320	Importantly, we show that selective targeting of glycans on CD11b with such lectins results in altered intracellular signaling events that inhibit TEpM and differentially affect key PMN inflammatory functions including phagocytosis, superoxide release and apoptosis.
31907993	8	79	theme	function	1544:1551	arg1	reduction					1557:1565	reduction	1557:1565	reduction of PMN-associated tissue damage in chronic inflammatory diseases	1557:1630	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	8	79	theme	function	1544:1551	arg1	manipulation					1522:1533	selective manipulation	1512:1533	selective manipulation of CD11b function	1512:1551	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	3	80	theme	transepithelial	490:504	arg1	migration					506:514	PMN transepithelial migration	486:514	PMN transepithelial migration	486:514	The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions.
31907993	4	81	from	targeting	588:596	arg1	CD11b					632:636	CD11b	632:636	CD11b	632:636	Previous studies have demonstrated that targeting of the N-linked glycan Lewis X on CD11b blocks PMN transepithelial migration (TEpM).
31907993	6	82	theme	Mannose	918:924	arg1	oligosaccharides					926:941	high Mannose oligosaccharides	913:941	high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin	913:984	Unusual glycan epitopes identified on CD11b/CD18 included high Mannose oligosaccharides recognized by the Galanthus Nivalis lectin and biantennary galactosylated N-glycans recognized by the Phaseolus Vulgaris erythroagglutinin lectin.
31907993	8	83	theme	PMN-associated	1570:1583	arg1	damage					1592:1597	PMN-associated tissue damage	1570:1597	PMN-associated tissue damage	1570:1597	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	3	84	theme	inflammatory	524:535	arg1	functions					537:545	PMN inflammatory functions	520:545	PMN inflammatory functions	520:545	The glycoprotein CD11b/CD18 plays a well-described role in regulating PMN transepithelial migration and PMN inflammatory functions.
31907993	8	85	theme	damage	1592:1597	arg1	reduction					1557:1565	reduction	1557:1565	reduction of PMN-associated tissue damage in chronic inflammatory diseases	1557:1630	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31907993	8	85	theme	damage	1592:1597	arg1	manipulation					1522:1533	selective manipulation	1512:1533	selective manipulation of CD11b function	1512:1551	Taken together, these data demonstrate that discrete glycan motifs expressed on CD11b/CD18 such as biantennary galactose could represent novel targets for selective manipulation of CD11b function and reduction of PMN-associated tissue damage in chronic inflammatory diseases.
31399531	4	0	theme	protein	865:871	arg1	C-R352Q					873:879	activated protein C-R352Q	855:879	activated protein C-R352Q	855:879	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	2	1	theme	C	339:339	arg1	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	1	2	theme	VIIIa	244:248	arg1	inactivation					213:224	protein S-dependent inactivation	193:224	protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis	193:271	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	6	3	theme	protein	1186:1192	arg1	S-deficient					1194:1204	protein S-deficient	1186:1204	protein S-deficient	1186:1204	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	8	4	theme	heterozygous	1891:1902	arg1	mutation					1904:1911	this compound heterozygous mutation	1877:1911	this compound heterozygous mutation	1877:1911	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	3	5	theme	heterozygous	502:513	arg1	c.1181G>A					547:555	c.1181G>A	547:555	c.1181G>A	547:555	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	5	theme	heterozygous	502:513	arg1	p.I73N					536:541	p.I73N	536:541	p.I73N	536:541	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	5	theme	heterozygous	502:513	arg1	c.344T>A					526:533	c.344T>A	526:533	c.344T>A	526:533	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	5	theme	heterozygous	502:513	arg1	mutations					515:523	compound heterozygous mutations	493:523	compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities	493:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	1	6	theme	limited	253:259	arg1	proteolysis					261:271	limited proteolysis	253:271	limited proteolysis	253:271	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	7	7	theme	metal	1726:1730	arg1	ions					1732:1735	metal ions	1726:1735	metal ions	1726:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	8	theme	reduced	1477:1483	arg1	activity					1485:1492	reduced activity	1477:1492	reduced activity in sub-physiological concentrations of Na+ and Ca2+	1477:1544	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	4	9	theme	catalytic	833:841	arg1	activity					843:850	protein S-dependent catalytic activity	813:850	protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va	813:896	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	7	10	theme	protein	1425:1431	arg1	C-R352Q					1454:1460	protein S. Activated protein C-R352Q	1425:1460	protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions	1425:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	5	11	dep	substitution	1012:1023	arg1	to					1005:1006	to	1005:1006	to	1005:1006	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	7	12	theme	C	1418:1418	arg1	interaction					1385:1395	interaction	1385:1395	interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions	1385:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	3	13	theme	protein	726:732	arg1	C					734:734	activated protein C	716:734	the resulting activated protein C mutants	702:742	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	2	14	theme	thrombosis	297:306	arg1	patient					308:314	a venous thrombosis patient	288:314	a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays	288:444	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	1	15	theme	anticoagulant	167:179	arg1	activity					181:188	its anticoagulant activity	163:188	its anticoagulant activity	163:188	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	7	16	theme	activated	1400:1408	arg1	C					1418:1418	activated protein C	1400:1418	activated protein C	1400:1418	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	3	17	theme	resulting	706:714	arg1	mutants					736:742	activated protein C mutants	716:742	the resulting activated protein C mutants	702:742	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	0	18	theme	protein	103:109	arg1	C					111:111	protein C	103:111	protein C	103:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	5	19	theme	C-I73N	1066:1071	arg1	interaction					1033:1043	interaction	1033:1043	interaction of activated protein C-I73N with protein S	1033:1086	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	7	20	from	activity	1485:1492	arg1	concentrations					1515:1528	sub-physiological concentrations	1497:1528	sub-physiological concentrations of Na+ and Ca2+	1497:1544	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	21	theme	adverse	1652:1658	arg1	effect					1660:1665	no apparent adverse effect	1640:1665	no apparent adverse effect on its function in the presence of physiological levels of metal ions	1640:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	0	22	from	site	71:74	arg1	EGF-domain					89:98	the first EGF-domain	79:98	the first EGF-domain of protein C	79:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	0	22	from	site	71:74	arg1	C					111:111	protein C	103:111	protein C	103:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	3	23	theme	normal	752:757	arg1	activities					786:795	normal amidolytic and proteolytic activities	752:795	normal amidolytic and proteolytic activities	752:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	5	24	theme	protein	1078:1084	arg1	S					1086:1086	protein S	1078:1086	protein S	1078:1086	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	1	25	theme	S-dependent	201:211	arg1	inactivation					213:224	protein S-dependent inactivation	193:224	protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis	193:271	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	5	26	theme	activated	1048:1056	arg1	C-I73N					1066:1071	activated protein C-I73N	1048:1071	activated protein C-I73N	1048:1071	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	7	27	theme	Activated	1436:1444	arg1	C-R352Q					1454:1460	protein S. Activated protein C-R352Q	1425:1460	protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions	1425:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	8	28	theme	I73N/R352Q	1796:1805	arg1	mutations					1807:1815	I73N/R352Q mutations	1796:1815	I73N/R352Q mutations in activated protein C	1796:1838	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	7	29	theme	protein	1346:1352	arg1	C					1354:1354	protein C	1346:1354	protein C	1346:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	2	30	theme	antigen	341:347	arg1	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	0	31	theme	N-linked	48:55	arg1	site					71:74	a new N-linked glycosylation site	42:74	a new N-linked glycosylation site on the first EGF-domain of protein C	42:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	7	32	theme	ions	1732:1735	arg1	levels					1716:1721	physiological levels	1702:1721	physiological levels of metal ions	1702:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	2	33	theme	clotting	430:437	arg1	assays					439:444	chromogenic and clotting assays	414:444	assays	439:444	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	8	34	theme	protein	1830:1836	arg1	C					1838:1838	activated protein C	1820:1838	activated protein C	1820:1838	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	1	35	theme	protein	146:152	arg1	C					154:154	Activated protein C	136:154	Activated protein C	136:154	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	7	36	theme	metal	1591:1595	arg1	affinity					1609:1616	metal ion-binding affinity	1591:1616	metal ion-binding affinity of the protease	1591:1632	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	0	37	gly	glycosylation	57:69	arg2	site					71:74	a new N-linked glycosylation site	42:74	a new N-linked glycosylation site on the first EGF-domain of protein C	42:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	7	38	theme	physiological	1702:1714	arg1	levels					1716:1721	physiological levels	1702:1721	physiological levels of metal ions	1702:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	4	39	theme	protein	954:960	arg1	C-I73N					962:967	activated protein C-I73N	944:967	activated protein C-I73N	944:967	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	2	40	theme	activity	366:373	arg1	levels					375:380	activity levels	366:380	activity levels of 44% and 23%	366:395	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	2	41	theme	%	360:360	arg1	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	2	41	theme	%	360:360	arg1	levels					375:380	activity levels	366:380	activity levels of 44% and 23%	366:395	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	0	42	theme	Ile73Asn	0:7	arg1	mutation					9:16	Ile73Asn mutation	0:16	Ile73Asn mutation in protein C	0:29	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	7	43	theme	EGF-like	1327:1334	arg1	domain					1336:1341	first EGF-like domain	1321:1341	first EGF-like domain of protein C	1321:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	43	theme	EGF-like	1327:1334	arg1	C					1354:1354	protein C	1346:1354	protein C	1346:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	2	44	theme	%	387:387	arg1	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	2	44	theme	%	387:387	arg1	levels					375:380	activity levels	366:380	activity levels of 44% and 23%	366:395	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	2	45	theme	chromogenic	414:424	arg1	assays					439:444	chromogenic and clotting assays	414:444	assays	439:444	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	3	46	theme	protein	601:607	arg1	mutations					611:619	protein C mutations	601:619	protein C mutations	601:619	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	5	47	theme	Asn	1008:1010	arg1	substitution					1012:1023	the Ile to Asn substitution	997:1023	the Ile to Asn substitution	997:1023	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	7	48	theme	glycosylation	1299:1311	arg1	site					1313:1316	a new glycosylation site	1293:1316	a new glycosylation site on first EGF-like domain of protein C	1293:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	49	theme	Further	1232:1238	arg1	analysis					1240:1247	Further analysis	1232:1247	Further analysis	1232:1247	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	4	50	theme	protein	813:819	arg1	activity					843:850	protein S-dependent catalytic activity	813:850	protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va	813:896	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	2	51	theme	protein	331:337	arg1	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	7	52	from	site	1313:1316	arg1	domain					1336:1341	first EGF-like domain	1321:1341	first EGF-like domain of protein C	1321:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	52	from	site	1313:1316	arg1	C					1354:1354	protein C	1346:1354	protein C	1346:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	6	53	theme	protein	1168:1174	arg1	C-I73N					1176:1181	activated protein C-I73N	1158:1181	activated protein C-I73N	1158:1181	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	1	54	theme	factors	229:235	arg1	Va					237:238	factors Va	229:238	factors Va	229:238	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	7	55	theme	sub-physiological	1497:1513	arg1	concentrations					1515:1528	sub-physiological concentrations	1497:1528	sub-physiological concentrations of Na+ and Ca2+	1497:1544	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	5	56	theme	Ile	1001:1003	arg1	substitution					1012:1023	the Ile to Asn substitution	997:1023	the Ile to Asn substitution	997:1023	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	8	57	theme	compound	1882:1889	arg1	mutation					1904:1911	this compound heterozygous mutation	1877:1911	this compound heterozygous mutation	1877:1911	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	3	58	theme	Genetic	447:453	arg1	analysis					455:462	Genetic analysis	447:462	Genetic analysis	447:462	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	4	59	theme	activated	855:863	arg1	C-R352Q					873:879	activated protein C-R352Q	855:879	activated protein C-R352Q	855:879	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	3	60	theme	compound	493:500	arg1	c.1181G>A					547:555	c.1181G>A	547:555	c.1181G>A	547:555	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	60	theme	compound	493:500	arg1	p.I73N					536:541	p.I73N	536:541	p.I73N	536:541	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	60	theme	compound	493:500	arg1	c.344T>A					526:533	c.344T>A	526:533	c.344T>A	526:533	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	60	theme	compound	493:500	arg1	mutations					515:523	compound heterozygous mutations	493:523	compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities	493:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	6	61	theme	activated	1158:1166	arg1	C-I73N					1176:1181	activated protein C-I73N	1158:1181	activated protein C-I73N	1158:1181	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	4	62	theme	C-R352Q	873:879	arg1	activity					843:850	protein S-dependent catalytic activity	813:850	protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va	813:896	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	7	63	theme	protein	1446:1452	arg1	C-R352Q					1454:1460	protein S. Activated protein C-R352Q	1425:1460	protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions	1425:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	4	64	theme	S-dependent	821:831	arg1	activity					843:850	protein S-dependent catalytic activity	813:850	protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va	813:896	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	7	65	theme	S.	1433:1434	arg1	C-R352Q					1454:1460	protein S. Activated protein C-R352Q	1425:1460	protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions	1425:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	3	66	theme	C	734:734	arg1	mutants					736:742	activated protein C mutants	716:742	the resulting activated protein C mutants	702:742	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	0	67	theme	C	111:111	arg1	EGF-domain					89:98	the first EGF-domain	79:98	the first EGF-domain of protein C	79:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	0	67	theme	C	111:111	arg1	C					111:111	protein C	103:111	protein C	103:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	2	68	theme	venous	290:295	arg1	patient					308:314	a venous thrombosis patient	288:314	a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays	288:444	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	7	69	theme	apparent	1643:1650	arg1	effect					1660:1665	no apparent adverse effect	1640:1665	no apparent adverse effect on its function in the presence of physiological levels of metal ions	1640:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	6	70	theme	anticoagulant	1131:1143	arg1	activity					1145:1152	a normal anticoagulant activity	1122:1152	a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma	1122:1229	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	8	71	from	mutations	1807:1815	arg1	C					1838:1838	activated protein C	1820:1838	activated protein C	1820:1838	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	3	72	theme	activated	716:724	arg1	C					734:734	activated protein C	716:734	the resulting activated protein C mutants	702:742	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	1	73	theme	protein	193:199	arg1	inactivation					213:224	protein S-dependent inactivation	193:224	protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis	193:271	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	7	74	from	function	1674:1681	arg1	presence					1690:1697	the presence	1686:1697	the presence of physiological levels of metal ions	1686:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	3	75	theme	amidolytic	759:768	arg1	activities					786:795	normal amidolytic and proteolytic activities	752:795	normal amidolytic and proteolytic activities	752:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	7	76	theme	protease	1625:1632	arg1	affinity					1609:1616	metal ion-binding affinity	1591:1616	metal ion-binding affinity of the protease	1591:1632	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	4	77	theme	factor	888:893	arg1	Va					895:896	factor Va	888:896	factor Va	888:896	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	6	78	theme	normal	1217:1222	arg1	plasma					1224:1229	normal plasma	1217:1229	normal plasma	1217:1229	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	3	79	from	mutations	515:523	arg1	PROC					570:573	PROC	570:573	PROC	570:573	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	0	80	theme	glycosylation	57:69	arg1	site					71:74	a new N-linked glycosylation site	42:74	a new N-linked glycosylation site on the first EGF-domain of protein C	42:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	5	81	theme	protein	1058:1064	arg1	C-I73N					1066:1071	activated protein C-I73N	1048:1071	activated protein C-I73N	1048:1071	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	3	82	dep	mutations	515:523	arg1	c.1181G>A					547:555	c.1181G>A	547:555	c.1181G>A	547:555	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	82	dep	mutations	515:523	arg1	p.I73N					536:541	p.I73N	536:541	p.I73N	536:541	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	82	dep	mutations	515:523	arg1	c.344T>A					526:533	c.344T>A	526:533	c.344T>A	526:533	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	82	dep	mutations	515:523	arg1	mutations					515:523	compound heterozygous mutations	493:523	compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities	493:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	82	dep	mutations	515:523	arg1	p.R352Q					558:564	p.R352Q	558:564	p.R352Q	558:564	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	7	83	theme	ion-binding	1597:1607	arg1	affinity					1609:1616	metal ion-binding affinity	1591:1616	metal ion-binding affinity of the protease	1591:1632	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	84	theme	C	1354:1354	arg1	domain					1336:1341	first EGF-like domain	1321:1341	first EGF-like domain of protein C	1321:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	84	theme	C	1354:1354	arg1	C					1354:1354	protein C	1346:1354	protein C	1346:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	3	85	theme	proteolytic	774:784	arg1	activities					786:795	normal amidolytic and proteolytic activities	752:795	normal amidolytic and proteolytic activities	752:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	2	86	contain	has	320:322	arg2	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	2	86	contain	has	320:322	arg2	levels					375:380	activity levels	366:380	activity levels of 44% and 23%	366:395	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	2	86	contain	has	320:322	arg1	patient					308:314	a venous thrombosis patient	288:314	a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays	288:444	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	1	87	theme	Activated	136:144	arg1	C					154:154	Activated protein C	136:154	Activated protein C	136:154	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
31399531	0	88	from	mutation	9:16	arg1	C					29:29	protein C	21:29	protein C	21:29	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	0	89	theme	first	83:87	arg1	EGF-domain					89:98	the first EGF-domain	79:98	the first EGF-domain of protein C	79:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	0	89	theme	first	83:87	arg1	C					111:111	protein C	103:111	protein C	103:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	7	90	gly	glycosylation	1299:1311	arg2	site					1313:1316	a new glycosylation site	1293:1316	a new glycosylation site on first EGF-like domain of protein C	1293:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	8	91	theme	activated	1820:1828	arg1	C					1838:1838	activated protein C	1820:1838	activated protein C	1820:1838	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	7	92	theme	protein	1410:1416	arg1	C					1418:1418	activated protein C	1400:1418	activated protein C	1400:1418	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	93	dep	substitution	1269:1280	arg1	to					1262:1263	to	1262:1263	to	1262:1263	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	94	with	interaction	1385:1395	arg1	C-R352Q					1454:1460	protein S. Activated protein C-R352Q	1425:1460	protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions	1425:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	95	theme	levels	1716:1721	arg1	presence					1690:1697	the presence	1686:1697	the presence of physiological levels of metal ions	1686:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	4	96	theme	activated	944:952	arg1	C-I73N					962:967	activated protein C-I73N	944:967	activated protein C-I73N	944:967	However, while protein S-dependent catalytic activity of activated protein C-R352Q toward factor Va was normal, it was significantly impaired for activated protein C-I73N.
31399531	5	97	with	interaction	1033:1043	arg1	S					1086:1086	protein S	1078:1086	protein S	1078:1086	These results suggest that the Ile to Asn substitution impairs interaction of activated protein C-I73N with protein S.
31399531	7	98	from	effect	1660:1665	arg1	function					1674:1681	its function	1670:1681	its function in the presence of physiological levels of metal ions	1670:1735	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	99	theme	first	1321:1325	arg1	domain					1336:1341	first EGF-like domain	1321:1341	first EGF-like domain of protein C	1321:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	7	99	theme	first	1321:1325	arg1	C					1354:1354	protein C	1346:1354	protein C	1346:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	2	100	theme	%	395:395	arg1	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	2	100	theme	%	395:395	arg1	levels					375:380	activity levels	366:380	activity levels of 44% and 23%	366:395	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	7	101	theme	Na+	1533:1535	arg1	concentrations					1515:1528	sub-physiological concentrations	1497:1528	sub-physiological concentrations of Na+ and Ca2+	1497:1544	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	6	102	from	activity	1145:1152	arg1	plasma					1224:1229	normal plasma	1217:1229	normal plasma	1217:1229	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	6	102	from	activity	1145:1152	arg1	S-deficient					1194:1204	protein S-deficient	1186:1204	protein S-deficient	1186:1204	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	0	103	theme	protein	21:27	arg1	C					29:29	protein C	21:29	protein C	21:29	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	7	104	theme	new	1295:1297	arg1	site					1313:1316	a new glycosylation site	1293:1316	a new glycosylation site on first EGF-like domain of protein C	1293:1354	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	3	105	contain	carries	485:491	arg2	p.I73N					536:541	p.I73N	536:541	p.I73N	536:541	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	105	contain	carries	485:491	arg1	proband					477:483	the proband	473:483	the proband	473:483	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	105	contain	carries	485:491	arg2	c.344T>A					526:533	c.344T>A	526:533	c.344T>A	526:533	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	105	contain	carries	485:491	arg2	mutations					515:523	compound heterozygous mutations	493:523	compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities	493:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	105	contain	carries	485:491	arg2	c.1181G>A					547:555	c.1181G>A	547:555	c.1181G>A	547:555	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	0	106	theme	new	44:46	arg1	site					71:74	a new N-linked glycosylation site	42:74	a new N-linked glycosylation site on the first EGF-domain of protein C	42:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	6	107	theme	normal	1124:1129	arg1	activity					1145:1152	a normal anticoagulant activity	1122:1152	a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma	1122:1229	This conclusion was supported by a normal anticoagulant activity for activated protein C-I73N in protein S-deficient but not in normal plasma.
31399531	2	108	theme	plasma	324:329	arg1	level					349:353	plasma protein C antigen level	324:353	plasma protein C antigen level of 63%	324:360	We identified a venous thrombosis patient who has plasma protein C antigen level of 63% and activity levels of 44% and 23%, as monitored by chromogenic and clotting assays.
31399531	7	109	theme	Ca2+	1541:1544	arg1	concentrations					1515:1528	sub-physiological concentrations	1497:1528	sub-physiological concentrations of Na+ and Ca2+	1497:1544	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	0	110	link	N-linked	48:55	arg1	site					71:74	a new N-linked glycosylation site	42:74	a new N-linked glycosylation site on the first EGF-domain of protein C	42:111	Ile73Asn mutation in protein C introduces a new N-linked glycosylation site on the first EGF-domain of protein C and causes thrombosis.
31399531	7	111	theme	Asn	1265:1267	arg1	substitution					1269:1280	Ile to Asn substitution	1258:1280	Ile to Asn substitution	1258:1280	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	3	112	theme	C	609:609	arg1	mutations					611:619	protein C mutations	601:619	protein C mutations	601:619	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	8	113	contain	carrying	1868:1875	arg2	mutation					1904:1911	this compound heterozygous mutation	1877:1911	this compound heterozygous mutation	1877:1911	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	8	113	contain	carrying	1868:1875	arg1	proband					1860:1866	proband	1860:1866	proband carrying this compound heterozygous mutation	1860:1911	These results provide insight into the mechanism by which I73N/R352Q mutations in activated protein C cause thrombosis in proband carrying this compound heterozygous mutation.
31399531	3	114	dep	PROC	570:573	arg1	expressed					591:599	expressed	591:599	individually expressed protein C mutations	578:619	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	3	114	dep	PROC	570:573	arg1	discovered					625:634	discovered	625:634	discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities	625:795	Genetic analysis revealed the proband carries compound heterozygous mutations (c.344T>A, p.I73N and c.1181G>A, p.R352Q) in PROC We individually expressed protein C mutations and discovered that thrombin-thrombomodulin activates both variants normally and the resulting activated protein C mutants exhibit normal amidolytic and proteolytic activities.
31399531	7	115	theme	Ile	1258:1260	arg1	substitution					1269:1280	Ile to Asn substitution	1258:1280	Ile to Asn substitution	1258:1280	Further analysis revealed Ile to Asn substitution introduces a new glycosylation site on first EGF-like domain of protein C, thereby adversely affecting interaction of activated protein C with protein S. Activated protein C-R352Q only exhibited reduced activity in sub-physiological concentrations of Na+ and Ca2+, suggesting that this residue contributes to metal ion-binding affinity of the protease, with no apparent adverse effect on its function in the presence of physiological levels of metal ions.
31399531	1	116	theme	Va	237:238	arg1	inactivation					213:224	protein S-dependent inactivation	193:224	protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis	193:271	Activated protein C exerts its anticoagulant activity by protein S-dependent inactivation of factors Va and VIIIa by limited proteolysis.
30581149	10	0	theme	inhibition	1536:1545	arg1	experiments					1547:1557	IgE-reactivity and inhibition experiments	1517:1557	experiments	1547:1557	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	1	from	epitopes	1737:1744	arg1	plants					1749:1754	plants	1749:1754	plants which were completely represented by HHM 2	1749:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	11	2	theme	Defined	1811:1817	arg1	HHM-glycoproteins					1831:1847	CONCLUSION Defined recombinant HHM-glycoproteins	1800:1847	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites	1800:1923	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	4	3	gly	N-glycosylation	690:704	arg2	sites					706:710	one or two N-glycosylation sites	679:710	one or two N-glycosylation sites	679:710	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	4	3	gly	N-glycosylation	690:704	arg2	two					686:688	two	686:688	two	686:688	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	4	3	gly	N-glycosylation	690:704	arg2	one					679:681	one	679:681	one	679:681	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	10	4	theme	IgE-reactivity	1517:1530	arg1	experiments					1547:1557	IgE-reactivity and inhibition experiments	1517:1557	experiments	1547:1557	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	3	5	theme	horse	591:595	arg1	myoglobin					603:611	the non-allergenic protein horse heart myoglobin	564:611	the non-allergenic protein horse heart myoglobin (HHM)	564:617	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	3	5	theme	horse	591:595	arg1	HHM					614:616	HHM	614:616	HHM	614:616	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	1	6	theme	allergenic	250:259	arg1	activity					261:268	allergenic activity	250:268	allergenic activity	250:268	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	10	7	from	plants	1749:1754	arg1	heterogeneity					1703:1715	a hitherto unknown heterogeneity	1684:1715	a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2	1684:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	3	8	theme	non-allergenic	568:581	arg1	myoglobin					603:611	the non-allergenic protein horse heart myoglobin	564:611	the non-allergenic protein horse heart myoglobin (HHM)	564:617	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	3	8	theme	non-allergenic	568:581	arg1	HHM					614:616	HHM	614:616	HHM	614:616	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	2	9	from	venoms	371:376	arg1	epitopes					357:364	carbohydrate-specific IgE epitopes	331:364	carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE	331:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	4	10	theme	N-glycosylation	690:704	arg1	sites					706:710	one or two N-glycosylation sites	679:710	one or two N-glycosylation sites	679:710	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	10	11	theme	epitopes	1737:1744	arg1	heterogeneity					1703:1715	a hitherto unknown heterogeneity	1684:1715	a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2	1684:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	8	12	theme	monomeric	1284:1292	arg1	HHM-glycovariants					1217:1233	RESULTS HHM-glycovariants	1209:1233	RESULTS HHM-glycovariants	1209:1233	RESULTS HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins.
30581149	8	12	theme	monomeric	1284:1292	arg1	proteins					1305:1312	monomeric and folded proteins	1284:1312	monomeric and folded proteins	1284:1312	RESULTS HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins.
30581149	2	13	from	pollen	379:384	arg1	epitopes					357:364	carbohydrate-specific IgE epitopes	331:364	carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE	331:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	10	14	theme	carbohydrate	1720:1731	arg1	epitopes					1737:1744	carbohydrate IgE epitopes	1720:1744	carbohydrate IgE epitopes in plants which were completely represented by HHM 2	1720:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	3	15	theme	myoglobin	603:611	arg1	N-terminus					550:559	the N-terminus	546:559	the N-terminus of the non-allergenic protein horse heart myoglobin (HHM)	546:617	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	5	16	theme	HHM	876:878	arg1	proteins					880:887	Recombinant HHM proteins	864:887	Recombinant HHM proteins	864:887	Recombinant HHM proteins were analyzed regarding fold and aggregation by circular dichroism and gel filtration, respectively.
30581149	8	17	theme	folded	1298:1303	arg1	HHM-glycovariants					1217:1233	RESULTS HHM-glycovariants	1209:1233	RESULTS HHM-glycovariants	1209:1233	RESULTS HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins.
30581149	8	17	theme	folded	1298:1303	arg1	proteins					1305:1312	monomeric and folded proteins	1284:1312	monomeric and folded proteins	1284:1312	RESULTS HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins.
30581149	11	18	theme	IgE	2016:2018	arg1	reactivity					2020:2029	peptide-specific IgE reactivity	1999:2029	peptide-specific IgE reactivity	1999:2029	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	3	19	theme	gene	635:638	arg1	technology					640:649	synthetic gene technology	625:649	synthetic gene technology	625:649	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	1	20	from	%	208:208	arg1	antibodies					189:198	IgE antibodies	185:198	IgE antibodies from >20% of allergic patients	185:229	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	6	21	theme	IgE	990:992	arg1	reactivity					994:1003	IgE reactivity	990:1003	IgE reactivity	990:1003	IgE reactivity was assessed by ELISA, immunoblotting and quantitative ImmunoCAP measurements.
30581149	4	22	theme	High-Five™	751:760	arg1	cells					769:773	baculovirus-infected High-Five™ insect cells	730:773	baculovirus-infected High-Five™ insect cells	730:773	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	9	23	theme	carbohydrate-specific	1356:1376	arg1	reactivity					1382:1391	carbohydrate-specific IgE reactivity	1356:1391	carbohydrate-specific IgE reactivity	1356:1391	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	5	24	theme	gel	960:962	arg1	filtration					964:973	gel filtration	960:973	gel filtration	960:973	Recombinant HHM proteins were analyzed regarding fold and aggregation by circular dichroism and gel filtration, respectively.
30581149	2	25	theme	allergenic	450:459	arg1	IgE					479:481	allergenic, peptide-specific IgE	450:481	allergenic, peptide-specific IgE	450:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	6	26	theme	ImmunoCAP	1060:1068	arg1	measurements					1070:1081	quantitative ImmunoCAP measurements	1047:1081	quantitative ImmunoCAP measurements	1047:1081	IgE reactivity was assessed by ELISA, immunoblotting and quantitative ImmunoCAP measurements.
30581149	1	27	from	mites	161:165	arg1	present					131:137	present	131:137	present	131:137	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	7	28	theme	carbohydrate	1182:1193	arg1	epitopes					1199:1206	mite-derived carbohydrate IgE epitopes	1169:1206	mite-derived carbohydrate IgE epitopes	1169:1206	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	10	29	theme	plant	1586:1590	arg1	glcyoallergens					1592:1605	plant glcyoallergens	1586:1605	plant glcyoallergens	1586:1605	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	4	30	theme	non-glycosylated	781:796	arg1	HHM					807:809	HHM 0	807:811	HHM 0	807:811	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	4	30	theme	non-glycosylated	781:796	arg1	version					798:804	a non-glycosylated version	779:804	a non-glycosylated version (HHM 0)	779:812	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	1	31	from	pollen	150:155	arg1	present					131:137	present	131:137	present	131:137	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	10	32	theme	d	1624:1624	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	32	theme	d	1624:1624	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	1	33	from	venoms	142:147	arg1	present					131:137	present	131:137	present	131:137	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	10	34	theme	p	1613:1613	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	34	theme	p	1613:1613	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	4	35	gly	glycosylation	843:855	arg2	motif					857:861	the glycosylation motif	839:861	the glycosylation motif	839:861	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	1	36	from	present	131:137	arg1	venoms					142:147	venoms	142:147	venoms	142:147	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	36	from	present	131:137	arg1	mites					161:165	mites	161:165	mites	161:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	36	from	present	131:137	arg1	pollen					150:155	pollen	150:155	pollen	150:155	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	37	theme	BACKGROUND	103:112	arg1	glycans					123:129	BACKGROUND N-linked glycans	103:129	BACKGROUND N-linked glycans present in venoms, pollen and mites	103:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	11	38	theme	IgE	1882:1884	arg1	epitopes					1886:1893	carbohydrate-specific IgE epitopes	1860:1893	carbohydrate-specific IgE epitopes	1860:1893	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	10	39	theme	r	1646:1646	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	39	theme	r	1646:1646	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	7	40	link	mite-derived	1169:1180	arg1	epitopes					1199:1206	mite-derived carbohydrate IgE epitopes	1169:1206	mite-derived carbohydrate IgE epitopes	1169:1206	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	9	41	theme	pollen	1471:1476	arg1	carbohydrates					1502:1514	pollen, venom and mite-derived carbohydrates	1471:1514	pollen, venom and mite-derived carbohydrates	1471:1514	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	10	42	theme	a	1635:1635	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	42	theme	a	1635:1635	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	4	43	contain	containing	668:677	arg2	sites					706:710	one or two N-glycosylation sites	679:710	one or two N-glycosylation sites	679:710	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	4	43	contain	containing	668:677	arg1	HHM					652:654	HHM 1	652:656	HHM 1	652:656	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	4	44	theme	glycosylation	843:855	arg1	motif					857:861	the glycosylation motif	839:861	the glycosylation motif	839:861	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	0	45	theme	IgE	59:61	arg1	epitopes					63:70	carbohydrate-specific IgE epitopes	37:70	carbohydrate-specific IgE epitopes	37:70	Recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites.
30581149	9	46	theme	venom	1479:1483	arg1	carbohydrates					1502:1514	pollen, venom and mite-derived carbohydrates	1471:1514	pollen, venom and mite-derived carbohydrates	1471:1514	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	0	47	gly	glycoproteins	12:24	arg1	glycoproteins					12:24	Recombinant glycoproteins	0:24	Recombinant glycoproteins	0:24	Recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites.
30581149	9	48	link	mite-derived	1489:1500	arg1	carbohydrates					1502:1514	pollen, venom and mite-derived carbohydrates	1471:1514	pollen, venom and mite-derived carbohydrates	1471:1514	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	2	49	dep	allergenic	450:459	arg1	peptide-specific					462:477	peptide-specific	462:477	peptide-specific	462:477	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	9	50	theme	mite-derived	1489:1500	arg1	carbohydrates					1502:1514	pollen, venom and mite-derived carbohydrates	1471:1514	pollen, venom and mite-derived carbohydrates	1471:1514	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	10	51	theme	a	1657:1657	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	51	theme	a	1657:1657	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	3	52	theme	N-glycosylation	503:517	arg1	sites					519:523	two N-glycosylation sites	499:523	two N-glycosylation sites	499:523	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	1	53	theme	allergic	213:220	arg1	patients					222:229	allergic patients	213:229	allergic patients	213:229	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	54	link	N-linked	114:121	arg1	glycans					123:129	BACKGROUND N-linked glycans	103:129	BACKGROUND N-linked glycans present in venoms, pollen and mites	103:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	55	attach	present	131:137	arg2	glycans					123:129	BACKGROUND N-linked glycans	103:129	BACKGROUND N-linked glycans present in venoms, pollen and mites	103:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	55	attach	present	131:137	arg1	venoms					142:147	venoms	142:147	venoms	142:147	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	55	attach	present	131:137	arg1	mites					161:165	mites	161:165	mites	161:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	55	attach	present	131:137	arg1	pollen					150:155	pollen	150:155	pollen	150:155	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	7	56	theme	IgE	1195:1197	arg1	epitopes					1199:1206	mite-derived carbohydrate IgE epitopes	1169:1206	mite-derived carbohydrate IgE epitopes	1169:1206	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	7	57	theme	mite-derived	1169:1180	arg1	epitopes					1199:1206	mite-derived carbohydrate IgE epitopes	1169:1206	mite-derived carbohydrate IgE epitopes	1169:1206	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	3	58	theme	protein	583:589	arg1	myoglobin					603:611	the non-allergenic protein horse heart myoglobin	564:611	the non-allergenic protein horse heart myoglobin (HHM)	564:617	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	3	58	theme	protein	583:589	arg1	HHM					614:616	HHM	614:616	HHM	614:616	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	10	59	theme	unknown	1695:1701	arg1	heterogeneity					1703:1715	a hitherto unknown heterogeneity	1684:1715	a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2	1684:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	11	60	theme	recombinant	1819:1829	arg1	HHM-glycoproteins					1831:1847	CONCLUSION Defined recombinant HHM-glycoproteins	1800:1847	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites	1800:1923	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	11	61	dep	Defined	1811:1817	arg1	CONCLUSION					1800:1809	CONCLUSION	1800:1809	CONCLUSION	1800:1809	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	1	62	theme	IgE	185:187	arg1	antibodies					189:198	IgE antibodies	185:198	IgE antibodies from >20% of allergic patients	185:229	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	8	63	theme	insect	1268:1273	arg1	cells					1275:1279	insect cells	1268:1279	insect cells	1268:1279	RESULTS HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins.
30581149	10	64	theme	IgE	1733:1735	arg1	epitopes					1737:1744	carbohydrate IgE epitopes	1720:1744	carbohydrate IgE epitopes in plants which were completely represented by HHM 2	1720:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	3	65	theme	heart	597:601	arg1	myoglobin					603:611	the non-allergenic protein horse heart myoglobin	564:611	the non-allergenic protein horse heart myoglobin (HHM)	564:617	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	3	65	theme	heart	597:601	arg1	HHM					614:616	HHM	614:616	HHM	614:616	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	5	66	theme	Recombinant	864:874	arg1	proteins					880:887	Recombinant HHM proteins	864:887	Recombinant HHM proteins	864:887	Recombinant HHM proteins were analyzed regarding fold and aggregation by circular dichroism and gel filtration, respectively.
30581149	3	67	theme	synthetic	625:633	arg1	technology					640:649	synthetic gene technology	625:649	synthetic gene technology	625:649	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	10	68	gly	heterogeneity	1703:1715	arg1	epitopes					1737:1744	carbohydrate IgE epitopes	1720:1744	carbohydrate IgE epitopes in plants which were completely represented by HHM 2	1720:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	7	69	theme	IgE	1084:1086	arg1	assays					1099:1104	IgE inhibition assays	1084:1104	IgE inhibition assays	1084:1104	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	1	70	theme	present	131:137	arg1	glycans					123:129	BACKGROUND N-linked glycans	103:129	BACKGROUND N-linked glycans present in venoms, pollen and mites	103:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	4	71	theme	baculovirus-infected	730:749	arg1	cells					769:773	baculovirus-infected High-Five™ insect cells	730:773	baculovirus-infected High-Five™ insect cells	730:773	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	11	72	theme	peptide-specific	1999:2014	arg1	reactivity					2020:2029	peptide-specific IgE reactivity	1999:2029	peptide-specific IgE reactivity	1999:2029	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	7	73	theme	inhibition	1088:1097	arg1	assays					1099:1104	IgE inhibition assays	1084:1104	IgE inhibition assays	1084:1104	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	9	74	theme	IgE	1378:1380	arg1	reactivity					1382:1391	carbohydrate-specific IgE reactivity	1356:1391	carbohydrate-specific IgE reactivity	1356:1391	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	2	75	theme	recombinant	294:304	arg1	glycoproteins					306:318	recombinant glycoproteins	294:318	recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE	294:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	1	76	dep	low	240:242	arg1	activity					261:268	allergenic activity	250:268	allergenic activity	250:268	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	4	77	theme	insect	762:767	arg1	cells					769:773	baculovirus-infected High-Five™ insect cells	730:773	baculovirus-infected High-Five™ insect cells	730:773	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	2	78	theme	IgE	353:355	arg1	epitopes					357:364	carbohydrate-specific IgE epitopes	331:364	carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE	331:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	5	79	theme	circular	937:944	arg1	dichroism					946:954	circular dichroism	937:954	circular dichroism	937:954	Recombinant HHM proteins were analyzed regarding fold and aggregation by circular dichroism and gel filtration, respectively.
30581149	6	80	theme	quantitative	1047:1058	arg1	measurements					1070:1081	quantitative ImmunoCAP measurements	1047:1081	quantitative ImmunoCAP measurements	1047:1081	IgE reactivity was assessed by ELISA, immunoblotting and quantitative ImmunoCAP measurements.
30581149	10	81	theme	glcyoallergens	1592:1605	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	81	theme	glcyoallergens	1592:1605	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	11	82	gly	HHM-glycoproteins	1831:1847	arg1	HHM-glycoproteins					1831:1847	CONCLUSION Defined recombinant HHM-glycoproteins	1800:1847	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites	1800:1923	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	9	83	theme	carbohydrate-specific	1415:1435	arg1	IgE					1437:1439	carbohydrate-specific IgE	1415:1439	carbohydrate-specific IgE	1415:1439	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	0	84	theme	Recombinant	0:10	arg1	glycoproteins					12:24	Recombinant glycoproteins	0:24	Recombinant glycoproteins	0:24	Recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites.
30581149	4	85	gly	non-glycosylated	781:796	arg1	HHM					807:809	HHM 0	807:811	HHM 0	807:811	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	4	85	gly	non-glycosylated	781:796	arg1	version					798:804	a non-glycosylated version	779:804	a non-glycosylated version (HHM 0)	779:812	HHM 1 and HHM 2 containing one or two N-glycosylation sites were expressed in baculovirus-infected High-Five™ insect cells and a non-glycosylated version (HHM 0) was obtained by mutating the glycosylation motif.
30581149	10	86	theme	4 > nCyn	1615:1622	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	86	theme	4 > nCyn	1615:1622	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	9	87	theme	IgE	1455:1457	arg1	epitopes					1459:1466	IgE epitopes	1455:1466	IgE epitopes of pollen, venom and mite-derived carbohydrates	1455:1514	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	2	88	gly	glycoproteins	306:318	arg1	glycoproteins					306:318	recombinant glycoproteins	294:318	recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE	294:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	10	89	theme	nPhl	1608:1611	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	89	theme	nPhl	1608:1611	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	0	90	theme	carbohydrate-specific	37:57	arg1	epitopes					63:70	carbohydrate-specific IgE epitopes	37:70	carbohydrate-specific IgE epitopes	37:70	Recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites.
30581149	1	91	theme	N-linked	114:121	arg1	glycans					123:129	BACKGROUND N-linked glycans	103:129	BACKGROUND N-linked glycans present in venoms, pollen and mites	103:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	92	contain	have	235:238	arg2	no					247:248	no	247:248	no	247:248	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	92	contain	have	235:238	arg2	low					240:242	low	240:242	low	240:242	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	92	contain	have	235:238	arg1	glycans					123:129	BACKGROUND N-linked glycans	103:129	BACKGROUND N-linked glycans present in venoms, pollen and mites	103:165	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	10	93	theme	2 > nJug	1637:1644	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	93	theme	2 > nJug	1637:1644	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	11	94	theme	carbohydrate-specific	1860:1880	arg1	epitopes					1886:1893	carbohydrate-specific IgE epitopes	1860:1893	carbohydrate-specific IgE epitopes	1860:1893	CONCLUSION Defined recombinant HHM-glycoproteins resembling carbohydrate-specific IgE epitopes from plants, venoms and mites were engineered which made it possible to discriminate carbohydrate- from peptide-specific IgE reactivity.
30581149	3	95	gly	N-glycosylation	503:517	arg2	two					499:501	two	499:501	two	499:501	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	3	95	gly	N-glycosylation	503:517	arg2	sites					519:523	two N-glycosylation sites	499:523	two N-glycosylation sites	499:523	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	7	96	with	cross-reactivity	1130:1145	arg1	plant					1159:1163	plant	1159:1163	plant	1159:1163	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	7	96	with	cross-reactivity	1130:1145	arg1	venom					1152:1156	venom	1152:1156	venom	1152:1156	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	7	96	with	cross-reactivity	1130:1145	arg1	epitopes					1199:1206	mite-derived carbohydrate IgE epitopes	1169:1206	mite-derived carbohydrate IgE epitopes	1169:1206	IgE inhibition assays were performed to study cross-reactivity with venom, plant and mite-derived carbohydrate IgE epitopes.
30581149	10	97	theme	1 > nPla	1626:1633	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	97	theme	1 > nPla	1626:1633	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	2	98	theme	carbohydrate-specific	419:439	arg1	IgE					441:443	carbohydrate-specific IgE	419:443	carbohydrate-specific IgE	419:443	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	2	99	from	mites	390:394	arg1	epitopes					357:364	carbohydrate-specific IgE epitopes	331:364	carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE	331:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	10	100	theme	1 > nCry	1659:1666	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	100	theme	1 > nCry	1659:1666	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	9	101	theme	carbohydrates	1502:1514	arg1	epitopes					1459:1466	IgE epitopes	1455:1466	IgE epitopes of pollen, venom and mite-derived carbohydrates	1455:1514	The HHM-glycovariants exhibited strictly carbohydrate-specific IgE reactivity, designed to quantify carbohydrate-specific IgE and resembled IgE epitopes of pollen, venom and mite-derived carbohydrates.
30581149	3	102	dep	METHODS	484:490	arg1	One					492:494	One	492:494	One	492:494	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	3	102	dep	METHODS	484:490	arg1	sites					519:523	two N-glycosylation sites	499:523	two N-glycosylation sites	499:523	METHODS One or two N-glycosylation sites were engineered into the N-terminus of the non-allergenic protein horse heart myoglobin (HHM) using synthetic gene technology.
30581149	10	103	theme	2 > nCup	1648:1655	arg1	hierarchy					1573:1581	a hierarchy	1571:1581	a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1)	1571:1671	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	10	103	theme	2 > nCup	1648:1655	arg1	j					1668:1668	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1	1608:1670	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
30581149	2	104	theme	carbohydrate-specific	331:351	arg1	epitopes					357:364	carbohydrate-specific IgE epitopes	331:364	carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE	331:481	OBJECTIVES To engineer recombinant glycoproteins resembling carbohydrate-specific IgE epitopes from venoms, pollen and mites which can discriminate carbohydrate-specific IgE from allergenic, peptide-specific IgE.
30581149	1	105	theme	patients	222:229	arg1	%					208:208	>20%	205:208	>20% of allergic patients	205:229	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	1	105	theme	patients	222:229	arg1	patients					222:229	allergic patients	213:229	allergic patients	213:229	BACKGROUND N-linked glycans present in venoms, pollen and mites are recognized by IgE antibodies from >20% of allergic patients but have low or no allergenic activity.
30581149	8	106	theme	RESULTS	1209:1215	arg1	HHM-glycovariants					1217:1233	RESULTS HHM-glycovariants	1209:1233	RESULTS HHM-glycovariants	1209:1233	RESULTS HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins.
30581149	8	106	theme	RESULTS	1209:1215	arg1	proteins					1305:1312	monomeric and folded proteins	1284:1312	monomeric and folded proteins	1284:1312	RESULTS HHM-glycovariants were expressed and purified from insect cells as monomeric and folded proteins.
30581149	10	107	from	heterogeneity	1703:1715	arg1	plants					1749:1754	plants	1749:1754	plants which were completely represented by HHM 2	1749:1797	IgE-reactivity and inhibition experiments established a hierarchy of plant glcyoallergens (nPhl p 4 > nCyn d 1 > nPla a 2 > nJug r 2 > nCup a 1 > nCry j 1) indicating a hitherto unknown heterogeneity of carbohydrate IgE epitopes in plants which were completely represented by HHM 2.
29038508	7	0	theme	receptor	1150:1157	arg1	expression					1133:1142	cell surface expression	1120:1142	cell surface expression of Fz receptor	1120:1157	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	3	1	theme	β-catenin	521:529	arg1	accumulation					505:516	nuclear accumulation	497:516	nuclear accumulation of β-catenin	497:529	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	4	2	theme	nuclear	616:622	arg1	accumulation					624:635	nuclear accumulation	616:635	nuclear accumulation of β-catenin	616:648	Conversely, knockdown of zebrafish otg using specific antisense morpholino promoted nuclear accumulation of β-catenin and caused ventralization.
29038508	0	3	theme	Frizzled8	83:91	arg1	Trafficking					68:78	Cell Membrane Trafficking	54:78	Cell Membrane Trafficking of Frizzled8	54:91	Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8.
29038508	6	4	theme	N-linked	949:956	arg1	glycosylation					958:970	N-linked glycosylation	949:970	N-linked glycosylation of Fz8	949:977	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	7	5	theme	Fz	1147:1148	arg1	receptor					1150:1157	Fz receptor	1147:1157	Fz receptor	1147:1157	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	4	6	theme	otg	567:569	arg1	knockdown					544:552	knockdown	544:552	knockdown of zebrafish otg using specific antisense morpholino	544:605	Conversely, knockdown of zebrafish otg using specific antisense morpholino promoted nuclear accumulation of β-catenin and caused ventralization.
29038508	6	7	theme	Fz8	855:857	arg1	receptor					860:867	Frizzled8 (Fz8) receptor	844:867	Frizzled8 (Fz8) receptor	844:867	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	2	8	theme	large-scale	287:297	arg1	screening					310:318	a large-scale expression screening	285:318	a large-scale expression screening of human cDNAs in zebrafish embryos	285:354	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	9	theme	expression	299:308	arg1	screening					310:318	a large-scale expression screening	285:318	a large-scale expression screening of human cDNAs in zebrafish embryos	285:354	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	10	theme	human	323:327	arg1	cDNAs					329:333	human cDNAs	323:333	human cDNAs	323:333	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	5	11	theme	headless-like	707:719	arg1	phenotype					721:729	headless-like phenotype	707:729	headless-like phenotype induced by inhibition of GSK-3β activity	707:770	However, OTG failed to rescue headless-like phenotype induced by inhibition of GSK-3β activity, suggesting that OTG acts upstream of GSK-3β.
29038508	1	12	theme	tissue/body	160:170	arg1	patterning					172:181	tissue/body patterning	160:181	tissue/body patterning	160:181	Wnt signaling controls critical developmental processes including tissue/body patterning.
29038508	7	13	theme	surface	1125:1131	arg1	expression					1133:1142	cell surface expression	1120:1142	cell surface expression of Fz receptor	1120:1157	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	6	14	theme	Frizzled8	844:852	arg1	receptor					860:867	Frizzled8 (Fz8) receptor	844:867	Frizzled8 (Fz8) receptor	844:867	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	6	15	link	N-linked	949:956	arg1	glycosylation					958:970	N-linked glycosylation	949:970	N-linked glycosylation of Fz8	949:977	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	7	16	theme	expression	1133:1142	arg1	modulation					1106:1115	the modulation	1102:1115	the modulation of cell surface expression of Fz receptor	1102:1157	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	3	17	theme	Wnt	465:467	arg1	genes					476:480	Wnt target genes	465:480	Wnt target genes	465:480	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	6	18	theme	endoplasmic	904:914	arg1	reticulum					916:924	the endoplasmic reticulum	900:924	the endoplasmic reticulum	900:924	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	1	19	theme	Wnt	94:96	arg1	signaling					98:106	Wnt signaling	94:106	Wnt signaling	94:106	Wnt signaling controls critical developmental processes including tissue/body patterning.
29038508	4	20	theme	specific	577:584	arg1	morpholino					596:605	specific antisense morpholino	577:605	specific antisense morpholino	577:605	Conversely, knockdown of zebrafish otg using specific antisense morpholino promoted nuclear accumulation of β-catenin and caused ventralization.
29038508	6	21	theme	Fz8	975:977	arg1	glycosylation					958:970	N-linked glycosylation	949:970	N-linked glycosylation of Fz8	949:977	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	6	22	from	retention	880:888	arg1	reticulum					916:924	the endoplasmic reticulum	900:924	the endoplasmic reticulum	900:924	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	3	23	theme	zebrafish	382:390	arg1	embryos					392:398	zebrafish embryos	382:398	zebrafish embryos	382:398	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	5	24	theme	GSK-3β	756:761	arg1	activity					763:770	GSK-3β activity	756:770	GSK-3β activity	756:770	However, OTG failed to rescue headless-like phenotype induced by inhibition of GSK-3β activity, suggesting that OTG acts upstream of GSK-3β.
29038508	1	25	theme	critical	117:124	arg1	processes					140:148	critical developmental processes	117:148	critical developmental processes	117:148	Wnt signaling controls critical developmental processes including tissue/body patterning.
29038508	7	26	theme	cell	1120:1123	arg1	expression					1133:1142	cell surface expression	1120:1142	cell surface expression of Fz receptor	1120:1157	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	4	27	theme	antisense	586:594	arg1	morpholino					596:605	specific antisense morpholino	577:605	specific antisense morpholino	577:605	Conversely, knockdown of zebrafish otg using specific antisense morpholino promoted nuclear accumulation of β-catenin and caused ventralization.
29038508	5	28	theme	activity	763:770	arg1	inhibition					742:751	inhibition	742:751	inhibition of GSK-3β activity	742:770	However, OTG failed to rescue headless-like phenotype induced by inhibition of GSK-3β activity, suggesting that OTG acts upstream of GSK-3β.
29038508	3	29	from	Overexpression	357:370	arg1	embryos					392:398	zebrafish embryos	382:398	zebrafish embryos	382:398	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	3	30	theme	target	469:474	arg1	genes					476:480	Wnt target genes	465:480	Wnt target genes	465:480	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	6	31	theme	Fz8	893:895	arg1	retention					880:888	retention	880:888	retention of Fz8 in the endoplasmic reticulum	880:924	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	7	32	theme	negative	1044:1051	arg1	OTG					1019:1021	OTG	1019:1021	OTG	1019:1021	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	7	32	theme	negative	1044:1051	arg1	regulator					1053:1061	a novel negative regulator	1036:1061	a novel negative regulator of Wnt signaling during development	1036:1097	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	3	33	theme	genes	476:480	arg1	expression					451:460	the expression	447:460	the expression of Wnt target genes	447:480	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	0	34	theme	Membrane	59:66	arg1	Trafficking					68:78	Cell Membrane Trafficking	54:78	Cell Membrane Trafficking of Frizzled8	54:91	Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8.
29038508	7	35	theme	signaling	1070:1078	arg1	OTG					1019:1021	OTG	1019:1021	OTG	1019:1021	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	7	35	theme	signaling	1070:1078	arg1	regulator					1053:1061	a novel negative regulator	1036:1061	a novel negative regulator of Wnt signaling during development	1036:1097	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	2	36	theme	signaling	246:254	arg1	OTTOGI					257:262	OTTOGI	257:262	OTTOGI (OTG)	257:268	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	36	theme	signaling	246:254	arg1	regulator					229:237	a novel regulator	221:237	a novel regulator of Wnt signaling	221:254	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	1	37	theme	developmental	126:138	arg1	processes					140:148	critical developmental processes	117:148	critical developmental processes	117:148	Wnt signaling controls critical developmental processes including tissue/body patterning.
29038508	0	38	theme	Cell	54:57	arg1	Trafficking					68:78	Cell Membrane Trafficking	54:78	Cell Membrane Trafficking of Frizzled8	54:91	Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8.
29038508	2	39	attach	isolated	271:278	arg1	screening					310:318	a large-scale expression screening	285:318	a large-scale expression screening of human cDNAs in zebrafish embryos	285:354	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	39	attach	isolated	271:278	arg2	regulator					229:237	a novel regulator	221:237	a novel regulator of Wnt signaling	221:254	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	39	attach	isolated	271:278	arg2	OTTOGI					257:262	OTTOGI	257:262	OTTOGI (OTG)	257:268	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	40	theme	Wnt	242:244	arg1	signaling					246:254	Wnt signaling	242:254	Wnt signaling	242:254	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	41	theme	zebrafish	338:346	arg1	embryos					348:354	zebrafish embryos	338:354	zebrafish embryos	338:354	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	4	42	theme	zebrafish	557:565	arg1	otg					567:569	zebrafish otg	557:569	zebrafish otg	557:569	Conversely, knockdown of zebrafish otg using specific antisense morpholino promoted nuclear accumulation of β-catenin and caused ventralization.
29038508	2	43	theme	regulator	229:237	arg1	identification					203:216	the identification	199:216	the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos	199:354	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	7	44	theme	novel	1038:1042	arg1	OTG					1019:1021	OTG	1019:1021	OTG	1019:1021	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	7	44	theme	novel	1038:1042	arg1	regulator					1053:1061	a novel negative regulator	1036:1061	a novel negative regulator of Wnt signaling during development	1036:1097	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	7	45	theme	Wnt	1066:1068	arg1	signaling					1070:1078	Wnt signaling	1066:1078	Wnt signaling	1066:1078	Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.
29038508	2	46	theme	novel	223:227	arg1	OTTOGI					257:262	OTTOGI	257:262	OTTOGI (OTG)	257:268	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	46	theme	novel	223:227	arg1	regulator					229:237	a novel regulator	221:237	a novel regulator of Wnt signaling	221:254	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	2	47	theme	cDNAs	329:333	arg1	screening					310:318	a large-scale expression screening	285:318	a large-scale expression screening of human cDNAs in zebrafish embryos	285:354	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	4	48	theme	β-catenin	640:648	arg1	accumulation					624:635	nuclear accumulation	616:635	nuclear accumulation of β-catenin	616:648	Conversely, knockdown of zebrafish otg using specific antisense morpholino promoted nuclear accumulation of β-catenin and caused ventralization.
29038508	6	49	gly	glycosylation	958:970	arg1	Fz8					975:977	Fz8	975:977	Fz8	975:977	OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8.
29038508	3	50	theme	nuclear	497:503	arg1	accumulation					505:516	nuclear accumulation	497:516	nuclear accumulation of β-catenin	497:529	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	3	51	theme	dorso-anteriorized	407:424	arg1	phenotype					426:434	dorso-anteriorized phenotype	407:434	dorso-anteriorized phenotype	407:434	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
29038508	0	52	theme	Wnt/β-catenin	16:28	arg1	Signaling					30:38	Wnt/β-catenin Signaling	16:38	Wnt/β-catenin Signaling	16:38	Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8.
29038508	2	53	from	screening	310:318	arg1	embryos					348:354	zebrafish embryos	338:354	zebrafish embryos	338:354	Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG), isolated from a large-scale expression screening of human cDNAs in zebrafish embryos.
29038508	3	54	theme	OTG	375:377	arg1	Overexpression					357:370	Overexpression	357:370	Overexpression of OTG in zebrafish embryos	357:398	Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin.
28883554	7	0	theme	H7N9	1237:1240	arg1	viruses					1258:1264	H7N9 NA stalk mutant viruses	1237:1264	H7N9 NA stalk mutant viruses	1237:1264	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	7	1	theme	H7N9	1120:1123	arg1	strain					1135:1140	a human-infecting H7N9 avian IAV strain	1102:1140	a human-infecting H7N9 avian IAV strain	1102:1140	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	1	2	from	birds	282:286	arg1	adaptation					217:226	evolutionary adaptation	204:226	evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry	204:306	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	3	3	theme	N-linked	511:518	arg1	glycosite					520:528	one potential N-linked glycosite	497:528	one potential N-linked glycosite from the NA stalk region	497:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	1	4	theme	stalk	171:175	arg1	truncation					177:186	neuraminidase (NA) stalk truncation	152:186	neuraminidase (NA) stalk truncation	152:186	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	2	5	from	alteration	338:347	arg1	mice					418:421	BALB/c mice	411:421	BALB/c mice	411:421	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	3	6	theme	NA	539:540	arg1	region					548:553	the NA stalk region	535:553	the NA stalk region	535:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	7	7	theme	NA	1143:1144	arg1	truncation					1152:1161	NA stalk truncation	1143:1161	NA stalk truncation	1143:1161	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	7	8	from	replication	1195:1205	arg1	model					1284:1288	the same mouse model	1269:1288	the same mouse model	1269:1288	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	8	9	theme	IAVs	1483:1486	arg1	adaptation					1469:1478	the evolutionary adaptation	1452:1478	the evolutionary adaptation of IAVs	1452:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	3	10	from	region	548:553	arg1	glycosite					520:528	one potential N-linked glycosite	497:528	one potential N-linked glycosite from the NA stalk region	497:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	5	11	theme	extensive	858:866	arg1	transformation					879:892	extensive pathologic transformation	858:892	extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice	858:982	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	6	12	theme	increased	989:997	arg1	pathogenicity					999:1011	The increased pathogenicity	985:1011	The increased pathogenicity of these NA stalk mutants	985:1037	The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets.
28883554	4	13	theme	stalk	676:680	arg1	viruses					689:695	NA stalk mutant viruses	673:695	NA stalk mutant viruses	673:695	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	5	14	theme	stalk	764:768	arg1	truncation					770:779	NA stalk truncation	761:779	NA stalk truncation	761:779	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	0	15	theme	influenza	106:114	arg1	viruses					118:124	influenza A viruses	106:124	influenza A viruses	106:124	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	8	16	theme	stalk	1335:1339	arg1	determinants					1393:1404	the pathogenic determinants	1378:1404	the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs	1378:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	16	theme	stalk	1335:1339	arg1	deglycosylation					1355:1369	deglycosylation	1355:1369	deglycosylation	1355:1369	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	16	theme	stalk	1335:1339	arg1	truncation					1341:1350	NA stalk truncation	1332:1350	NA stalk truncation	1332:1350	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	2	17	theme	pandemic	380:387	arg1	virus					394:398	a 2009 pandemic H1N1 virus	373:398	a 2009 pandemic H1N1 virus (pH1N1)	373:406	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	2	17	theme	pandemic	380:387	arg1	pH1N1					401:405	pH1N1	401:405	pH1N1	401:405	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	0	18	theme	viruses	118:124	arg1	pathogenicity					89:101	enhanced pathogenicity	80:101	enhanced pathogenicity of influenza A viruses	80:124	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	0	19	theme	Adaptive	0:7	arg1	mutations					9:17	Adaptive mutations	0:17	Adaptive mutations of neuraminidase stalk truncation and deglycosylation	0:71	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	5	20	theme	systemic	917:924	arg1	infection					926:934	systemic infection	917:934	systemic infection	917:934	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	4	21	theme	reverse	722:728	arg1	genetics					730:737	reverse genetics	722:737	reverse genetics	722:737	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	3	22	theme	mouse-adapted	428:440	arg1	pH1N1					442:446	The mouse-adapted pH1N1	424:446	The mouse-adapted pH1N1	424:446	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	7	23	theme	stalk	1146:1150	arg1	truncation					1152:1161	NA stalk truncation	1143:1161	NA stalk truncation	1143:1161	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	1	24	theme	aquatic	274:280	arg1	birds					282:286	wild aquatic birds	269:286	wild aquatic birds	269:286	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	6	25	theme	mutants	1031:1037	arg1	pathogenicity					999:1011	The increased pathogenicity	985:1011	The increased pathogenicity of these NA stalk mutants	985:1037	The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets.
28883554	7	26	theme	mouse	1278:1282	arg1	model					1284:1288	the same mouse model	1269:1288	the same mouse model	1269:1288	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	2	27	theme	virus	394:398	arg1	adaptation					359:368	the adaptation	355:368	the adaptation of a 2009 pandemic H1N1 virus (pH1N1)	355:406	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	0	28	theme	stalk	36:40	arg1	truncation					42:51	neuraminidase stalk truncation	22:51	neuraminidase stalk truncation	22:51	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	5	29	theme	NA	761:762	arg1	truncation					770:779	NA stalk truncation	761:779	NA stalk truncation	761:779	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	6	30	theme	NA	1022:1023	arg1	mutants					1031:1037	these NA stalk mutants	1016:1037	these NA stalk mutants	1016:1037	The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets.
28883554	2	31	theme	molecular	328:336	arg1	alteration					338:347	this molecular alteration	323:347	this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice	323:421	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	7	32	theme	IAV	1131:1133	arg1	strain					1135:1140	a human-infecting H7N9 avian IAV strain	1102:1140	a human-infecting H7N9 avian IAV strain	1102:1140	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	4	33	dep	truncation	596:605	arg1	changes					651:657	changes	651:657	changes	651:657	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	7	34	theme	same	1273:1276	arg1	model					1284:1288	the same mouse model	1269:1288	the same mouse model	1269:1288	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	4	35	with	deglycosylation	610:624	arg1	pathogenicity					637:649	viral pathogenicity	631:649	viral pathogenicity	631:649	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	8	36	theme	seasonal	1409:1416	arg1	viruses					1428:1434	seasonal influenza viruses	1409:1434	seasonal influenza viruses associated with the evolutionary adaptation of IAVs	1409:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	1	37	theme	neuraminidase	152:164	arg1	truncation					177:186	neuraminidase (NA) stalk truncation	152:186	neuraminidase (NA) stalk truncation	152:186	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	4	38	with	truncation	596:605	arg1	pathogenicity					637:649	viral pathogenicity	631:649	viral pathogenicity	631:649	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	8	39	theme	viruses	1428:1434	arg1	determinants					1393:1404	the pathogenic determinants	1378:1404	the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs	1378:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	39	theme	viruses	1428:1434	arg1	deglycosylation					1355:1369	deglycosylation	1355:1369	deglycosylation	1355:1369	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	39	theme	viruses	1428:1434	arg1	truncation					1341:1350	NA stalk truncation	1332:1350	NA stalk truncation	1332:1350	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	1	40	theme	influenza	237:245	arg1	IAVs					258:261	IAVs	258:261	IAVs	258:261	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	1	40	theme	influenza	237:245	arg1	viruses					249:255	avian influenza A viruses	231:255	avian influenza A viruses (IAVs)	231:262	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	0	41	theme	deglycosylation	57:71	arg1	mutations					9:17	Adaptive mutations	0:17	Adaptive mutations of neuraminidase stalk truncation and deglycosylation	0:71	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	7	42	theme	mutant	1251:1256	arg1	viruses					1258:1264	H7N9 NA stalk mutant viruses	1237:1264	H7N9 NA stalk mutant viruses	1237:1264	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	4	43	theme	NA	587:588	arg1	truncation					596:605	NA stalk truncation	587:605	NA stalk truncation	587:605	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	7	44	theme	human-infecting	1104:1118	arg1	strain					1135:1140	a human-infecting H7N9 avian IAV strain	1102:1140	a human-infecting H7N9 avian IAV strain	1102:1140	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	3	45	theme	amino	475:479	arg1	glycosite					520:528	one potential N-linked glycosite	497:528	one potential N-linked glycosite from the NA stalk region	497:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	3	45	theme	amino	475:479	arg1	acids					481:485	its eight consecutive amino acids	453:485	its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region	453:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	5	46	from	organs	969:974	arg1	mice					979:982	mice	979:982	mice	979:982	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	1	47	theme	viruses	249:255	arg1	adaptation					217:226	evolutionary adaptation	204:226	evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry	204:306	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	7	48	theme	NA	1242:1243	arg1	viruses					1258:1264	H7N9 NA stalk mutant viruses	1237:1264	H7N9 NA stalk mutant viruses	1237:1264	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	7	49	theme	further	1074:1080	arg1	investigation					1082:1094	further investigation	1074:1094	further investigation using a human-infecting H7N9 avian IAV strain	1074:1140	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	3	50	theme	potential	501:509	arg1	glycosite					520:528	one potential N-linked glycosite	497:528	one potential N-linked glycosite from the NA stalk region	497:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	4	51	theme	viral	631:635	arg1	pathogenicity					637:649	viral pathogenicity	631:649	viral pathogenicity	631:649	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	3	52	theme	stalk	542:546	arg1	region					548:553	the NA stalk region	535:553	the NA stalk region	535:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	4	53	theme	truncation	596:605	arg1	relationship					571:582	the relationship	567:582	the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes	567:657	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	5	54	theme	lethal	821:826	arg1	virus					828:832	a lethal virus	819:832	a lethal virus	819:832	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	8	55	theme	evolutionary	1456:1467	arg1	adaptation					1469:1478	the evolutionary adaptation	1452:1478	the evolutionary adaptation of IAVs	1452:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	4	56	theme	deglycosylation	610:624	arg1	relationship					571:582	the relationship	567:582	the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes	567:657	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	4	57	theme	mutant	682:687	arg1	viruses					689:695	NA stalk mutant viruses	673:695	NA stalk mutant viruses	673:695	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	5	58	theme	mouse	901:905	arg1	lungs					907:911	mouse lungs	901:911	mouse lungs	901:911	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	7	59	from	pathogenicity	1220:1232	arg1	model					1284:1288	the same mouse model	1269:1288	the same mouse model	1269:1288	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	0	60	theme	enhanced	80:87	arg1	pathogenicity					89:101	enhanced pathogenicity	80:101	enhanced pathogenicity of influenza A viruses	80:124	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	3	61	gly	glycosite	520:528	arg2	glycosite					520:528	one potential N-linked glycosite	497:528	one potential N-linked glycosite from the NA stalk region	497:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	5	62	theme	pathologic	868:877	arg1	transformation					879:892	extensive pathologic transformation	858:892	extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice	858:982	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	4	63	theme	NA	673:674	arg1	viruses					689:695	NA stalk mutant viruses	673:695	NA stalk mutant viruses	673:695	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	0	64	theme	A	116:116	arg1	viruses					118:124	influenza A viruses	106:124	influenza A viruses	106:124	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	5	65	from	transformation	879:892	arg1	infection					926:934	systemic infection	917:934	systemic infection	917:934	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	5	65	from	transformation	879:892	arg1	lungs					907:911	mouse lungs	901:911	mouse lungs	901:911	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	3	66	link	N-linked	511:518	arg1	glycosite					520:528	one potential N-linked glycosite	497:528	one potential N-linked glycosite from the NA stalk region	497:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	5	67	dep	lungs	907:911	arg1	the					897:899	the	897:899	the	897:899	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	5	68	theme	respiratory	957:967	arg1	organs					969:974	the respiratory organs	953:974	the respiratory organs in mice	953:982	Intriguingly, either NA stalk truncation or deglycosylation changed pH1N1 into a lethal virus to mice by resulting in extensive pathologic transformation in the mouse lungs and systemic infection affecting beyond the respiratory organs in mice.
28883554	8	69	theme	NA	1332:1333	arg1	determinants					1393:1404	the pathogenic determinants	1378:1404	the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs	1378:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	69	theme	NA	1332:1333	arg1	deglycosylation					1355:1369	deglycosylation	1355:1369	deglycosylation	1355:1369	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	69	theme	NA	1332:1333	arg1	truncation					1341:1350	NA stalk truncation	1332:1350	NA stalk truncation	1332:1350	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	2	70	theme	BALB/c	411:416	arg1	mice					418:421	BALB/c mice	411:421	BALB/c mice	411:421	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	4	71	theme	pH1N1	704:708	arg1	backbone					710:717	the pH1N1 backbone	700:717	the pH1N1 backbone by reverse genetics	700:737	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	0	72	theme	neuraminidase	22:34	arg1	truncation					42:51	neuraminidase stalk truncation	22:51	neuraminidase stalk truncation	22:51	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	1	73	theme	wild	269:272	arg1	birds					282:286	wild aquatic birds	269:286	wild aquatic birds	269:286	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	0	74	theme	truncation	42:51	arg1	mutations					9:17	Adaptive mutations	0:17	Adaptive mutations of neuraminidase stalk truncation and deglycosylation	0:71	Adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza A viruses.
28883554	1	75	theme	evolutionary	204:215	arg1	adaptation					217:226	evolutionary adaptation	204:226	evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry	204:306	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	6	76	theme	stalk	1025:1029	arg1	mutants					1031:1037	these NA stalk mutants	1016:1037	these NA stalk mutants	1016:1037	The increased pathogenicity of these NA stalk mutants was also reproduced in ferrets.
28883554	2	77	theme	H1N1	389:392	arg1	virus					394:398	a 2009 pandemic H1N1 virus	373:398	a 2009 pandemic H1N1 virus (pH1N1)	373:406	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	2	77	theme	H1N1	389:392	arg1	pH1N1					401:405	pH1N1	401:405	pH1N1	401:405	We identified this molecular alteration after the adaptation of a 2009 pandemic H1N1 virus (pH1N1) in BALB/c mice.
28883554	7	78	theme	avian	1125:1129	arg1	strain					1135:1140	a human-infecting H7N9 avian IAV strain	1102:1140	a human-infecting H7N9 avian IAV strain	1102:1140	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	1	79	theme	domestic	291:298	arg1	poultry					300:306	domestic poultry	291:306	domestic poultry	291:306	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	8	80	theme	pathogenic	1382:1391	arg1	determinants					1393:1404	the pathogenic determinants	1378:1404	the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs	1378:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	80	theme	pathogenic	1382:1391	arg1	deglycosylation					1355:1369	deglycosylation	1355:1369	deglycosylation	1355:1369	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	8	80	theme	pathogenic	1382:1391	arg1	truncation					1341:1350	NA stalk truncation	1332:1350	NA stalk truncation	1332:1350	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	3	81	theme	consecutive	463:473	arg1	glycosite					520:528	one potential N-linked glycosite	497:528	one potential N-linked glycosite from the NA stalk region	497:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	3	81	theme	consecutive	463:473	arg1	acids					481:485	its eight consecutive amino acids	453:485	its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region	453:553	The mouse-adapted pH1N1 lost its eight consecutive amino acids including one potential N-linked glycosite from the NA stalk region.
28883554	7	82	theme	viruses	1258:1264	arg1	replication					1195:1205	the replication property and pathogenicity	1191:1232	replication	1195:1205	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	7	82	theme	viruses	1258:1264	arg1	pathogenicity					1220:1232	pathogenicity	1220:1232	pathogenicity	1220:1232	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	7	83	dep	replication	1195:1205	arg1	property					1207:1214	property	1207:1214	property	1207:1214	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	1	84	theme	avian	231:235	arg1	IAVs					258:261	IAVs	258:261	IAVs	258:261	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	1	84	theme	avian	231:235	arg1	viruses					249:255	avian influenza A viruses	231:255	avian influenza A viruses (IAVs)	231:262	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	7	85	theme	stalk	1245:1249	arg1	viruses					1258:1264	H7N9 NA stalk mutant viruses	1237:1264	H7N9 NA stalk mutant viruses	1237:1264	In further investigation using a human-infecting H7N9 avian IAV strain, NA stalk truncation or deglycosylation enhanced the replication property and pathogenicity of H7N9 NA stalk mutant viruses in the same mouse model.
28883554	4	86	theme	stalk	590:594	arg1	truncation					596:605	NA stalk truncation	587:605	NA stalk truncation	587:605	To explore the relationship of NA stalk truncation or deglycosylation with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics.
28883554	8	87	theme	influenza	1418:1426	arg1	viruses					1428:1434	seasonal influenza viruses	1409:1434	seasonal influenza viruses associated with the evolutionary adaptation of IAVs	1409:1486	Taken together, our results suggest that NA stalk truncation or deglycosylation can be the pathogenic determinants of seasonal influenza viruses associated with the evolutionary adaptation of IAVs.
28883554	1	88	theme	A	247:247	arg1	IAVs					258:261	IAVs	258:261	IAVs	258:261	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
28883554	1	88	theme	A	247:247	arg1	viruses					249:255	avian influenza A viruses	231:255	avian influenza A viruses (IAVs)	231:262	It has been noticed that neuraminidase (NA) stalk truncation has arisen from evolutionary adaptation of avian influenza A viruses (IAVs) from wild aquatic birds to domestic poultry.
31306674	4	0	theme	maturation	695:704	arg1	effects					684:690	the effects	680:690	the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors	680:864	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	9	1	from	important	1493:1501	arg1	cycle					1522:1526	the dengue life cycle	1506:1526	the dengue life cycle	1506:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	1	2	theme	enveloped	150:158	arg1	viruses					160:166	many enveloped viruses	145:166	many enveloped viruses	145:166	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	9	3	theme	key	1454:1456	arg1	receptors					1483:1491	some key glycosylated host immune receptors	1449:1491	some key glycosylated host immune receptors important in the dengue life cycle	1449:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	0	4	theme	dengue	74:79	arg1	virus					81:85	dengue virus	74:85	dengue virus	74:85	Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus.
31306674	4	5	with	IL-4	711:714	arg1	NB-DNJ					779:784	NB-DNJ	779:784	NB-DNJ	779:784	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	5	with	IL-4	711:714	arg1	N-butyl-1-deoxynojirimycin					751:776	N-butyl-1-deoxynojirimycin	751:776	N-butyl-1-deoxynojirimycin (NB-DNJ)	751:785	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	5	with	IL-4	711:714	arg1	MON-DNJ					816:822	MON-DNJ	816:822	MON-DNJ	816:822	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	5	with	IL-4	711:714	arg1	-1-DNJ					808:813	N-(9-methoxynonyl)-1-DNJ	790:813	N-(9-methoxynonyl)-1-DNJ (MON-DNJ)	790:823	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	6	theme	macrophage	845:854	arg1	receptors					856:864	11 macrophage receptors	842:864	11 macrophage receptors	842:864	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	7	7	dep	receptor	1192:1199	arg1	the					1183:1185	the	1183:1185	the	1183:1185	Treatment also affected signalling of the IFNγ receptor and TNFα receptor.
31306674	4	8	from	effects	684:690	arg1	expression					828:837	expression	828:837	expression of 11 macrophage receptors	828:864	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	9	theme	receptors	856:864	arg1	expression					828:837	expression	828:837	expression of 11 macrophage receptors	828:864	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	7	10	theme	receptor	1210:1217	arg1	signalling					1169:1178	signalling	1169:1178	signalling of the IFNγ receptor and TNFα receptor	1169:1217	Treatment also affected signalling of the IFNγ receptor and TNFα receptor.
31306674	5	11	theme	surface	992:998	arg1	receptor					1005:1012	surface IFNγ receptor	992:1012	surface IFNγ receptor	992:1012	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	3	12	theme	DENV	549:552	arg1	attachment					554:563	DENV attachment	549:563	DENV attachment	549:563	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	3	13	from	attachment	554:563	arg1	important					536:544	important	536:544	important	536:544	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	9	14	theme	host	1471:1474	arg1	receptors					1483:1491	some key glycosylated host immune receptors	1449:1491	some key glycosylated host immune receptors important in the dengue life cycle	1449:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	4	15	with	maturation	695:704	arg1	IL-4					711:714	IL-4	711:714	IL-4	711:714	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	15	with	maturation	695:704	arg1	treatment					736:744	treatment	736:744	treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ)	736:823	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	15	with	maturation	695:704	arg1	DENV-infection					717:730	DENV-infection	717:730	DENV-infection	717:730	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	5	16	theme	DENV	955:958	arg1	infection					960:968	DENV infection	955:968	DENV infection	955:968	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	1	17	gly	glycoproteins	236:248	arg1	glycoproteins					236:248	viral N-linked glycoproteins	221:248	viral N-linked glycoproteins	221:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	2	18	theme	infection	366:374	arg1	treatment					333:341	Iminosugar treatment	322:341	Iminosugar treatment of dengue virus (DENV) infection	322:374	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	9	19	theme	dengue	1510:1515	arg1	cycle					1522:1526	the dengue life cycle	1506:1526	the dengue life cycle	1506:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	1	20	theme	host	272:275	arg1	reticulum					289:297	host endoplasmic reticulum	272:297	host endoplasmic reticulum α-glucosidase enzymes	272:319	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	4	21	theme	macrophage	628:637	arg1	model					639:643	a primary human macrophage model	612:643	a primary human macrophage model of DENV infection	612:661	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	3	22	theme	important	536:544	arg1	receptors					526:534	host receptors	521:534	host receptors important in DENV attachment and uptake and immune responses to DENV	521:603	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	2	23	theme	virions	408:414	arg1	secretion					395:403	reduced secretion	387:403	reduced secretion of virions and hence lower viral titres	387:443	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	7	24	theme	TNFα	1205:1208	arg1	receptor					1210:1217	TNFα receptor	1205:1217	TNFα receptor	1205:1217	Treatment also affected signalling of the IFNγ receptor and TNFα receptor.
31306674	6	25	theme	iminosugar	1123:1132	arg1	treatment					1134:1142	iminosugar treatment	1123:1142	iminosugar treatment	1123:1142	This effect required infectious DENV and was reversed by iminosugar treatment.
31306674	1	26	link	N-linked	227:234	arg1	glycoproteins					236:248	viral N-linked glycoproteins	221:248	viral N-linked glycoproteins	221:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	2	27	theme	dengue	346:351	arg1	DENV					360:363	DENV	360:363	DENV	360:363	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	2	27	theme	dengue	346:351	arg1	virus					353:357	dengue virus	346:357	dengue virus (DENV) infection	346:374	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	4	28	theme	infection	653:661	arg1	model					639:643	a primary human macrophage model	612:643	a primary human macrophage model of DENV infection	612:661	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	7	29	theme	IFNγ	1187:1190	arg1	receptor					1192:1199	IFNγ receptor	1187:1199	IFNγ receptor	1187:1199	Treatment also affected signalling of the IFNγ receptor and TNFα receptor.
31306674	9	30	theme	life	1517:1520	arg1	cycle					1522:1526	the dengue life cycle	1506:1526	the dengue life cycle	1506:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	7	31	theme	receptor	1192:1199	arg1	signalling					1169:1178	signalling	1169:1178	signalling of the IFNγ receptor and TNFα receptor	1169:1217	Treatment also affected signalling of the IFNγ receptor and TNFα receptor.
31306674	1	32	theme	endoplasmic	277:287	arg1	reticulum					289:297	host endoplasmic reticulum	272:297	host endoplasmic reticulum α-glucosidase enzymes	272:319	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	8	33	theme	ligand	1253:1258	arg1	binding					1260:1266	ligand binding	1253:1266	ligand binding	1253:1266	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	3	34	theme	immune	580:585	arg1	responses					587:595	immune responses	580:595	immune responses to DENV	580:603	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	3	35	from	responses	587:595	arg1	important					536:544	important	536:544	important	536:544	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	2	36	theme	reduced	387:393	arg1	secretion					395:403	reduced secretion	387:403	reduced secretion of virions and hence lower viral titres	387:443	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	1	37	theme	reticulum	289:297	arg1	enzymes					313:319	host endoplasmic reticulum α-glucosidase enzymes	272:319	host endoplasmic reticulum α-glucosidase enzymes	272:319	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	8	38	theme	mannose	1319:1325	arg1	receptor					1327:1334	the mannose receptor	1315:1334	the mannose receptor	1315:1334	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	5	39	theme	any	924:926	arg1	expression					910:919	surface expression	902:919	surface expression of any of the receptors examined	902:952	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	1	40	theme	antiviral	92:100	arg1	consequence					192:202	a consequence	190:202	a consequence of misfolding of viral N-linked glycoproteins	190:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	1	40	theme	antiviral	92:100	arg1	mechanism					102:110	The antiviral mechanism	88:110	The antiviral mechanism of action of iminosugars against many enveloped viruses	88:166	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	2	41	theme	viral	432:436	arg1	titres					438:443	hence lower viral titres	420:443	hence lower viral titres	420:443	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	2	42	theme	titres	438:443	arg1	secretion					395:403	reduced secretion	387:403	reduced secretion of virions and hence lower viral titres	387:443	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	1	43	theme	α-glucosidase	299:311	arg1	enzymes					313:319	host endoplasmic reticulum α-glucosidase enzymes	272:319	host endoplasmic reticulum α-glucosidase enzymes	272:319	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	9	44	theme	immune	1476:1481	arg1	receptors					1483:1491	some key glycosylated host immune receptors	1449:1491	some key glycosylated host immune receptors important in the dengue life cycle	1449:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	2	45	theme	lower	426:430	arg1	titres					438:443	hence lower viral titres	420:443	hence lower viral titres	420:443	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	1	46	theme	enzymes	313:319	arg1	inhibition					258:267	inhibition	258:267	inhibition of host endoplasmic reticulum α-glucosidase enzymes	258:319	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	8	47	theme	receptor	1327:1334	arg1	receptor					1327:1334	the mannose receptor	1315:1334	the mannose receptor	1315:1334	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	8	47	theme	receptor	1327:1334	arg1	domain					1305:1310	the carbohydrate receptor-binding domain	1271:1310	the carbohydrate receptor-binding domain of the mannose receptor	1271:1334	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	4	48	theme	DENV	648:651	arg1	infection					653:661	DENV infection	648:661	DENV infection	648:661	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	6	49	theme	infectious	1087:1096	arg1	DENV					1098:1101	infectious DENV	1087:1101	infectious DENV	1087:1101	This effect required infectious DENV and was reversed by iminosugar treatment.
31306674	9	50	theme	primary	1389:1395	arg1	macrophages					1397:1407	primary macrophages	1389:1407	primary macrophages	1389:1407	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	9	51	theme	glycosylated	1458:1469	arg1	receptors					1483:1491	some key glycosylated host immune receptors	1449:1491	some key glycosylated host immune receptors important in the dengue life cycle	1449:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	4	52	theme	human	622:626	arg1	model					639:643	a primary human macrophage model	612:643	a primary human macrophage model of DENV infection	612:661	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	9	53	from	cycle	1522:1526	arg1	important					1493:1501	important	1493:1501	important	1493:1501	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	1	54	theme	misfolding	207:216	arg1	consequence					192:202	a consequence	190:202	a consequence of misfolding of viral N-linked glycoproteins	190:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	1	54	theme	misfolding	207:216	arg1	mechanism					102:110	The antiviral mechanism	88:110	The antiviral mechanism of action of iminosugars against many enveloped viruses	88:166	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	0	55	theme	γ	60:60	arg1	receptor					62:69	the interferon γ receptor	45:69	the interferon γ receptor	45:69	Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus.
31306674	9	56	theme	macrophages	1397:1407	arg1	treatment					1376:1384	iminosugar treatment	1365:1384	iminosugar treatment of primary macrophages	1365:1407	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	9	57	theme	iminosugar	1365:1374	arg1	treatment					1376:1384	iminosugar treatment	1365:1384	iminosugar treatment of primary macrophages	1365:1407	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	9	58	theme	receptors	1483:1491	arg1	functionality					1432:1444	functionality	1432:1444	functionality	1432:1444	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	9	58	theme	receptors	1483:1491	arg1	expression					1417:1426	expression	1417:1426	expression	1417:1426	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	5	59	theme	surface	902:908	arg1	expression					910:919	surface expression	902:919	surface expression of any of the receptors examined	902:952	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	0	60	theme	interferon	49:58	arg1	receptor					62:69	the interferon γ receptor	45:69	the interferon γ receptor	45:69	Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus.
31306674	4	61	with	treatment	736:744	arg1	NB-DNJ					779:784	NB-DNJ	779:784	NB-DNJ	779:784	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	61	with	treatment	736:744	arg1	N-butyl-1-deoxynojirimycin					751:776	N-butyl-1-deoxynojirimycin	751:776	N-butyl-1-deoxynojirimycin (NB-DNJ)	751:785	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	61	with	treatment	736:744	arg1	MON-DNJ					816:822	MON-DNJ	816:822	MON-DNJ	816:822	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	61	with	treatment	736:744	arg1	-1-DNJ					808:813	N-(9-methoxynonyl)-1-DNJ	790:813	N-(9-methoxynonyl)-1-DNJ (MON-DNJ)	790:823	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	5	62	theme	total	1039:1043	arg1	expression					1054:1063	total receptor expression	1039:1063	total receptor expression	1039:1063	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	1	63	theme	action	115:120	arg1	consequence					192:202	a consequence	190:202	a consequence of misfolding of viral N-linked glycoproteins	190:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	1	63	theme	action	115:120	arg1	mechanism					102:110	The antiviral mechanism	88:110	The antiviral mechanism of action of iminosugars against many enveloped viruses	88:166	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	5	64	theme	receptor	1045:1052	arg1	expression					1054:1063	total receptor expression	1039:1063	total receptor expression	1039:1063	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	9	65	gly	glycosylated	1458:1469	arg1	receptors					1483:1491	some key glycosylated host immune receptors	1449:1491	some key glycosylated host immune receptors important in the dengue life cycle	1449:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	5	66	theme	other	1022:1026	arg1	changes					1028:1034	other changes	1022:1034	other changes to total receptor expression	1022:1063	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	2	67	theme	virus	353:357	arg1	infection					366:374	dengue virus (DENV) infection	346:374	dengue virus (DENV) infection	346:374	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	2	68	theme	Iminosugar	322:331	arg1	treatment					333:341	Iminosugar treatment	322:341	Iminosugar treatment of dengue virus (DENV) infection	322:374	Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo.
31306674	9	69	theme	important	1493:1501	arg1	receptors					1483:1491	some key glycosylated host immune receptors	1449:1491	some key glycosylated host immune receptors important in the dengue life cycle	1449:1526	This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle.
31306674	4	70	theme	N-	790:791	arg1	MON-DNJ					816:822	MON-DNJ	816:822	MON-DNJ	816:822	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	70	theme	N-	790:791	arg1	-1-DNJ					808:813	N-(9-methoxynonyl)-1-DNJ	790:813	N-(9-methoxynonyl)-1-DNJ (MON-DNJ)	790:823	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	1	71	theme	iminosugars	125:135	arg1	action					115:120	action	115:120	action of iminosugars against many enveloped viruses	115:166	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	1	72	theme	viral	221:225	arg1	glycoproteins					236:248	viral N-linked glycoproteins	221:248	viral N-linked glycoproteins	221:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	8	73	theme	receptor-binding	1288:1303	arg1	receptor					1327:1334	the mannose receptor	1315:1334	the mannose receptor	1315:1334	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	8	73	theme	receptor-binding	1288:1303	arg1	domain					1305:1310	the carbohydrate receptor-binding domain	1271:1310	the carbohydrate receptor-binding domain of the mannose receptor	1271:1334	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	5	74	theme	IFNγ	1000:1003	arg1	receptor					1005:1012	surface IFNγ receptor	992:1012	surface IFNγ receptor	992:1012	Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFNγ receptor amongst other changes to total receptor expression.
31306674	8	75	theme	carbohydrate	1275:1286	arg1	receptor					1327:1334	the mannose receptor	1315:1334	the mannose receptor	1315:1334	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	8	75	theme	carbohydrate	1275:1286	arg1	domain					1305:1310	the carbohydrate receptor-binding domain	1271:1310	the carbohydrate receptor-binding domain of the mannose receptor	1271:1334	In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor.
31306674	3	76	theme	host	521:524	arg1	receptors					526:534	host receptors	521:534	host receptors important in DENV attachment and uptake and immune responses to DENV	521:603	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	3	77	from	uptake	569:574	arg1	important					536:544	important	536:544	important	536:544	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	1	78	theme	N-linked	227:234	arg1	glycoproteins					236:248	viral N-linked glycoproteins	221:248	viral N-linked glycoproteins	221:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	0	79	theme	receptor	62:69	arg1	downregulation					27:40	the downregulation	23:40	the downregulation of the interferon γ receptor by dengue virus	23:85	Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus.
31306674	4	80	with	DENV-infection	717:730	arg1	NB-DNJ					779:784	NB-DNJ	779:784	NB-DNJ	779:784	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	80	with	DENV-infection	717:730	arg1	N-butyl-1-deoxynojirimycin					751:776	N-butyl-1-deoxynojirimycin	751:776	N-butyl-1-deoxynojirimycin (NB-DNJ)	751:785	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	80	with	DENV-infection	717:730	arg1	MON-DNJ					816:822	MON-DNJ	816:822	MON-DNJ	816:822	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	80	with	DENV-infection	717:730	arg1	-1-DNJ					808:813	N-(9-methoxynonyl)-1-DNJ	790:813	N-(9-methoxynonyl)-1-DNJ (MON-DNJ)	790:823	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	4	81	theme	primary	614:620	arg1	model					639:643	a primary human macrophage model	612:643	a primary human macrophage model of DENV infection	612:661	Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors.
31306674	1	82	theme	many	145:148	arg1	viruses					160:166	many enveloped viruses	145:166	many enveloped viruses	145:166	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
31306674	3	83	from	important	536:544	arg1	uptake					569:574	uptake	569:574	uptake	569:574	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	3	83	from	important	536:544	arg1	responses					587:595	immune responses	580:595	immune responses to DENV	580:603	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	3	83	from	important	536:544	arg1	attachment					554:563	DENV attachment	549:563	DENV attachment	549:563	We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV.
31306674	1	84	theme	glycoproteins	236:248	arg1	misfolding					207:216	misfolding	207:216	misfolding of viral N-linked glycoproteins	207:248	The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes.
30952089	1	0	theme	cell	127:130	arg1	death					132:136	Programmed cell death 1	116:138	Programmed cell death 1	116:138	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	6	1	theme	sites	958:962	arg1	sites					958:962	the four potential N-linked glycosylation sites	916:962	the four potential N-linked glycosylation sites	916:962	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	6	1	theme	sites	958:962	arg1	three					907:911	three	907:911	three	907:911	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	6	2	mod	modifications	864:876	arg3	Glycosylation					850:862	Glycosylation modifications	850:876	Glycosylation modifications of PD-1	850:884	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	6	2	mod	modifications	864:876	arg1	PD-1					881:884	PD-1	881:884	PD-1	881:884	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	5	3	theme	molecules	839:847	arg1	development					781:791	the development	777:791	the development of PD-1-specific biologics and small chemical molecules	777:847	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	4	4	theme	multiple	617:624	arg1	interactions					626:637	multiple interactions	617:637	multiple interactions with PD-L1	617:648	Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1.
30952089	4	5	theme	structural	511:520	arg1	information					522:532	Complex structural information	503:532	Complex structural information	503:532	Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1.
30952089	0	6	theme	Monoclonal	58:67	arg1	Antibodies					69:78	Therapeutic Monoclonal Antibodies	46:78	Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy	46:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	6	7	theme	Glycosylation	850:862	arg1	modifications					864:876	Glycosylation modifications	850:876	Glycosylation modifications of PD-1	850:884	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	6	8	theme	N-linked	935:942	arg1	sites					958:962	the four potential N-linked glycosylation sites	916:962	the four potential N-linked glycosylation sites	916:962	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	0	9	theme	Therapeutic	46:56	arg1	Antibodies					69:78	Therapeutic Monoclonal Antibodies	46:78	Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy	46:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	4	10	with	interactions	626:637	arg1	PD-L1					644:648	PD-L1	644:648	PD-L1	644:648	Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1.
30952089	2	11	theme	hotspots	291:298	arg1	Identification					268:281	Identification	268:281	Identification of the "hotspots" on PD-1 for mAbs	268:316	Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy.
30952089	6	12	theme	potential	925:933	arg1	sites					958:962	the four potential N-linked glycosylation sites	916:962	the four potential N-linked glycosylation sites	916:962	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	8	13	theme	mAbs	1118:1121	arg1	mechanism					1095:1103	the mechanism	1091:1103	the mechanism of anti-PD-1 mAbs	1091:1121	These findings broaden our understanding of the mechanism of anti-PD-1 mAbs and provide insight into the development of agents targeting PD-1.
30952089	4	14	theme	PD-1	588:591	arg1	loop					580:583	the FG loop	573:583	the FG loop	573:583	Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1.
30952089	8	15	theme	anti-PD-1	1108:1116	arg1	mAbs					1118:1121	anti-PD-1 mAbs	1108:1121	anti-PD-1 mAbs	1108:1121	These findings broaden our understanding of the mechanism of anti-PD-1 mAbs and provide insight into the development of agents targeting PD-1.
30952089	5	16	theme	PD-1-specific	796:808	arg1	biologics					810:818	PD-1-specific biologics	796:818	PD-1-specific biologics	796:818	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	0	17	theme	FG	4:5	arg1	Loop					7:10	The FG Loop	0:10	The FG Loop of PD-1	0:18	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	0	17	theme	FG	4:5	arg1	"					40:40	a "Hotspot"	30:40	a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy	30:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	5	18	theme	varied	684:689	arg1	conformations					691:703	substantially varied conformations	670:703	substantially varied conformations	670:703	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	6	19	link	N-linked	935:942	arg1	sites					958:962	the four potential N-linked glycosylation sites	916:962	the four potential N-linked glycosylation sites	916:962	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	5	20	theme	biologics	810:818	arg1	development					781:791	the development	777:791	the development of PD-1-specific biologics and small chemical molecules	777:847	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	5	21	theme	FG	655:656	arg1	loop					658:661	The FG loop	651:661	The FG loop	651:661	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	2	22	theme	deliverable	360:370	arg1	agents					372:377	next-generation oral deliverable agents	339:377	next-generation oral deliverable agents with long-lasting efficacy	339:404	Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy.
30952089	1	23	theme	center	218:223	arg1	stage					225:229	center stage	218:229	center stage	218:229	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	0	24	theme	Immune	89:94	arg1	Therapy					107:113	Tumor Immune Checkpoint Therapy	83:113	Tumor Immune Checkpoint Therapy	83:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	3	25	theme	PD-1/PD-L1-blocking	473:491	arg1	efficacy					493:500	PD-1/PD-L1-blocking efficacy	473:500	PD-1/PD-L1-blocking efficacy	473:500	Here, we identified two PD-1-targeting mAbs, GY-5 and GY-14, with PD-1/PD-L1-blocking efficacy.
30952089	2	26	theme	next-generation	339:353	arg1	agents					372:377	next-generation oral deliverable agents	339:377	next-generation oral deliverable agents with long-lasting efficacy	339:404	Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy.
30952089	2	27	theme	oral	355:358	arg1	agents					372:377	next-generation oral deliverable agents	339:377	next-generation oral deliverable agents with long-lasting efficacy	339:404	Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy.
30952089	4	28	theme	Complex	503:509	arg1	information					522:532	Complex structural information	503:532	Complex structural information	503:532	Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1.
30952089	0	29	theme	Tumor	83:87	arg1	Therapy					107:113	Tumor Immune Checkpoint Therapy	83:113	Tumor Immune Checkpoint Therapy	83:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	3	30	theme	PD-1-targeting	431:444	arg1	mAbs					446:449	two PD-1-targeting mAbs	427:449	two PD-1-targeting mAbs	427:449	Here, we identified two PD-1-targeting mAbs, GY-5 and GY-14, with PD-1/PD-L1-blocking efficacy.
30952089	3	30	theme	PD-1-targeting	431:444	arg1	GY-14					461:465	GY-14	461:465	GY-14	461:465	Here, we identified two PD-1-targeting mAbs, GY-5 and GY-14, with PD-1/PD-L1-blocking efficacy.
30952089	3	30	theme	PD-1-targeting	431:444	arg1	GY-5					452:455	GY-5	452:455	GY-5	452:455	Here, we identified two PD-1-targeting mAbs, GY-5 and GY-14, with PD-1/PD-L1-blocking efficacy.
30952089	7	31	theme	GY-14	998:1002	arg1	binding					978:984	the binding	974:984	the binding of GY-5 and GY-14 to PD-1	974:1010	However, the binding of GY-5 and GY-14 to PD-1 was not affected by glycosylation.
30952089	6	32	located	observed	895:902	arg2	modifications					864:876	Glycosylation modifications	850:876	Glycosylation modifications of PD-1	850:884	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	6	32	located	observed	895:902	arg1	sites					958:962	the four potential N-linked glycosylation sites	916:962	the four potential N-linked glycosylation sites	916:962	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	6	32	located	observed	895:902	arg1	three					907:911	three	907:911	three	907:911	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	0	33	theme	PD-1	15:18	arg1	Loop					7:10	The FG Loop	0:10	The FG Loop of PD-1	0:18	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	0	33	theme	PD-1	15:18	arg1	"					40:40	a "Hotspot"	30:40	a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy	30:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	1	34	theme	tumor	235:239	arg1	therapy					259:265	tumor immune checkpoint therapy	235:265	tumor immune checkpoint therapy	235:265	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	0	35	theme	Checkpoint	96:105	arg1	Therapy					107:113	Tumor Immune Checkpoint Therapy	83:113	Tumor Immune Checkpoint Therapy	83:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	6	36	theme	glycosylation	944:956	arg1	sites					958:962	the four potential N-linked glycosylation sites	916:962	the four potential N-linked glycosylation sites	916:962	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	5	37	theme	novel	749:753	arg1	region					766:771	a novel targetable region	747:771	a novel targetable region	747:771	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	6	38	gly	glycosylation	944:956	arg2	four					920:923	four	920:923	four	920:923	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	6	38	gly	glycosylation	944:956	arg2	sites					958:962	the four potential N-linked glycosylation sites	916:962	the four potential N-linked glycosylation sites	916:962	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	4	39	theme	FG	577:578	arg1	loop					580:583	the FG loop	573:583	the FG loop	573:583	Complex structural information revealed that both mAbs mainly bind to the FG loop of PD-1, which also contributes multiple interactions with PD-L1.
30952089	8	40	theme	agents	1167:1172	arg1	development					1152:1162	the development	1148:1162	the development of agents targeting PD-1	1148:1187	These findings broaden our understanding of the mechanism of anti-PD-1 mAbs and provide insight into the development of agents targeting PD-1.
30952089	1	41	theme	immune	241:246	arg1	therapy					259:265	tumor immune checkpoint therapy	235:265	tumor immune checkpoint therapy	235:265	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	7	42	theme	GY-5	989:992	arg1	binding					978:984	the binding	974:984	the binding of GY-5 and GY-14 to PD-1	974:1010	However, the binding of GY-5 and GY-14 to PD-1 was not affected by glycosylation.
30952089	1	43	dep	-blocking	168:176	arg1	death					132:136	Programmed cell death 1	116:138	Programmed cell death 1	116:138	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	2	44	theme	long-lasting	384:395	arg1	efficacy					397:404	long-lasting efficacy	384:404	long-lasting efficacy	384:404	Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy.
30952089	1	45	theme	checkpoint	248:257	arg1	therapy					259:265	tumor immune checkpoint therapy	235:265	tumor immune checkpoint therapy	235:265	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	0	46	from	Antibodies	69:78	arg1	Therapy					107:113	Tumor Immune Checkpoint Therapy	83:113	Tumor Immune Checkpoint Therapy	83:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	5	47	theme	different	721:729	arg1	mAbs					731:734	different mAbs	721:734	different mAbs	721:734	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	2	48	with	agents	372:377	arg1	efficacy					397:404	long-lasting efficacy	384:404	long-lasting efficacy	384:404	Identification of the "hotspots" on PD-1 for mAbs will help to develop next-generation oral deliverable agents with long-lasting efficacy.
30952089	5	49	theme	chemical	830:837	arg1	molecules					839:847	small chemical molecules	824:847	small chemical molecules	824:847	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	1	50	theme	-blocking	168:176	arg1	mAbs					201:204	mAbs	201:204	mAbs	201:204	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	1	50	theme	-blocking	168:176	arg1	antibodies					189:198	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies	116:198	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs)	116:205	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	0	51	theme	Hotspot	33:39	arg1	"					40:40	a "Hotspot"	30:40	a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy	30:113	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	0	51	theme	Hotspot	33:39	arg1	Loop					7:10	The FG Loop	0:10	The FG Loop of PD-1	0:18	The FG Loop of PD-1 Serves as a "Hotspot" for Therapeutic Monoclonal Antibodies in Tumor Immune Checkpoint Therapy.
30952089	5	52	theme	small	824:828	arg1	molecules					839:847	small chemical molecules	824:847	small chemical molecules	824:847	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	1	53	theme	monoclonal	178:187	arg1	mAbs					201:204	mAbs	201:204	mAbs	201:204	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	1	53	theme	monoclonal	178:187	arg1	antibodies					189:198	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies	116:198	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs)	116:205	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	6	54	theme	PD-1	881:884	arg1	modifications					864:876	Glycosylation modifications	850:876	Glycosylation modifications of PD-1	850:884	Glycosylation modifications of PD-1 could be observed in three of the four potential N-linked glycosylation sites.
30952089	5	55	theme	targetable	755:764	arg1	region					766:771	a novel targetable region	747:771	a novel targetable region	747:771	The FG loop adopts substantially varied conformations upon binding to different mAbs, providing a novel targetable region for the development of PD-1-specific biologics and small chemical molecules.
30952089	1	56	theme	Programmed	116:125	arg1	death					132:136	Programmed cell death 1	116:138	Programmed cell death 1	116:138	Programmed cell death 1 (PD-1)/PD-1 ligand-1 (PD-L1)-blocking monoclonal antibodies (mAbs) have taken center stage for tumor immune checkpoint therapy.
30952089	8	57	theme	mechanism	1095:1103	arg1	understanding					1074:1086	our understanding	1070:1086	our understanding of the mechanism of anti-PD-1 mAbs	1070:1121	These findings broaden our understanding of the mechanism of anti-PD-1 mAbs and provide insight into the development of agents targeting PD-1.
30884134	7	0	theme	cell	1574:1577	arg1	survival					1579:1586	cell survival	1574:1586	cell survival	1574:1586	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	6	1	dep	positive	1414:1421	arg1	to					1423:1424	to	1423:1424	to	1423:1424	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	6	1	dep	positive	1414:1421	arg1	negative					1426:1433	negative	1426:1433	negative	1426:1433	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	4	2	theme	carcinoma	949:957	arg1	cells					969:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	4	3	theme	N-glycosylation	791:805	arg1	inhibition					807:816	N-glycosylation inhibition	791:816	N-glycosylation inhibition	791:816	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	4	4	theme	OVCAR-3	960:966	arg1	cells					969:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	0	5	from	analysis	8:15	arg1	response					45:52	response	45:52	response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line	45:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	4	6	theme	tunicamycin	916:926	arg1	cells					969:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	3	7	theme	cell	515:518	arg1	responses					520:528	these cell responses	509:528	these cell responses	509:528	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	0	8	theme	drug-resistant	96:109	arg1	line					134:137	a drug-resistant ovarian carcinoma cell line	94:137	a drug-resistant ovarian carcinoma cell line	94:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	7	9	theme	N-glycosylation	1555:1569	arg1	significance					1539:1550	the significance	1535:1550	the significance of N-glycosylation to cell survival	1535:1586	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	5	10	theme	proteins	1086:1093	arg1	expression					1059:1068	the expression	1055:1068	the expression of glycosylated proteins	1055:1093	The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins.
30884134	5	11	theme	N-glycosylation	1002:1016	arg1	inhibition					1018:1027	N-glycosylation inhibition	1002:1027	N-glycosylation inhibition	1002:1027	The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins.
30884134	4	12	theme	proteome	759:766	arg1	alterations					768:778	the dynamic proteome alterations	747:778	the dynamic proteome alterations related to N-glycosylation inhibition	747:816	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	1	13	theme	great	265:269	arg1	potential					271:279	great potential	265:279	great potential for cancer treatment	265:300	Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment.
30884134	6	14	theme	ER	1228:1229	arg1	stress					1231:1236	ER stress	1228:1236	ER stress	1228:1236	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	4	15	theme	related	780:786	arg1	alterations					768:778	the dynamic proteome alterations	747:778	the dynamic proteome alterations related to N-glycosylation inhibition	747:816	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	3	16	theme	related	565:571	arg1	timeline					497:504	the detailed timeline	484:504	the detailed timeline of these cell responses	484:528	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	3	16	theme	related	565:571	arg1	explicit					610:617	explicit	610:617	explicit	610:617	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	2	17	theme	endoplasmic	341:351	arg1	ER					364:365	ER	364:365	ER	364:365	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	2	17	theme	endoplasmic	341:351	arg1	reticulum					353:361	endoplasmic reticulum	341:361	endoplasmic reticulum (ER) stress	341:373	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	0	18	theme	carcinoma	119:127	arg1	line					134:137	a drug-resistant ovarian carcinoma cell line	94:137	a drug-resistant ovarian carcinoma cell line	94:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	0	19	from	response	45:52	arg1	analysis					8:15	Dynamic analysis	0:15	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.	0:138	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	4	20	theme	proteomics	895:904	arg1	data					906:909	our previously published quantitative proteomics data	857:909	our previously published quantitative proteomics data	857:909	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	3	21	theme	protein	534:540	arg1	alterations					553:563	protein expression alterations	534:563	protein expression alterations	534:563	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	2	22	theme	protein	392:398	arg1	response					400:407	the unfolded protein response	379:407	the unfolded protein response (UPR)	379:413	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	2	22	theme	protein	392:398	arg1	UPR					410:412	UPR	410:412	UPR	410:412	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	0	23	theme	ovarian	111:117	arg1	line					134:137	a drug-resistant ovarian carcinoma cell line	94:137	a drug-resistant ovarian carcinoma cell line	94:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	4	24	theme	quantitative	882:893	arg1	data					906:909	our previously published quantitative proteomics data	857:909	our previously published quantitative proteomics data	857:909	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	2	25	theme	ER	440:441	arg1	apoptosis					458:466	ER stress-related apoptosis	440:466	ER stress-related apoptosis	440:466	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	6	26	theme	Functional	1142:1151	arg1	annotation					1153:1162	Functional annotation	1142:1162	Functional annotation of these altered proteins	1142:1188	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	2	27	theme	stress-related	443:456	arg1	apoptosis					458:466	ER stress-related apoptosis	440:466	ER stress-related apoptosis	440:466	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	0	28	from	alterations	30:40	arg1	response					45:52	response	45:52	response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line	45:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	4	29	theme	dynamic	751:757	arg1	alterations					768:778	the dynamic proteome alterations	747:778	the dynamic proteome alterations related to N-glycosylation inhibition	747:816	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	7	30	theme	significance	1539:1550	arg1	understanding					1518:1530	better understanding	1511:1530	better understanding of the significance of N-glycosylation to cell survival	1511:1586	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	7	30	theme	significance	1539:1550	arg1	treatment					1610:1618	TM-related cancer treatment	1592:1618	TM-related cancer treatment	1592:1618	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	1	31	theme	antitumor	193:201	arg1	drugs					203:207	antitumor drugs	193:207	antitumor drugs	193:207	Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment.
30884134	0	32	theme	Dynamic	0:6	arg1	analysis					8:15	Dynamic analysis	0:15	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.	0:138	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	6	33	theme	stress-related	1312:1325	arg1	apoptosis					1327:1335	ER stress-related apoptosis	1309:1335	ER stress-related apoptosis	1309:1335	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	5	34	theme	extended	1114:1121	arg1	scale					1123:1127	an extended scale	1111:1127	an extended scale of proteins	1111:1139	The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins.
30884134	2	35	theme	N-glycosylation	317:331	arg1	Inhibition					303:312	Inhibition	303:312	Inhibition of N-glycosylation	303:331	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	6	36	theme	cellular	1391:1398	arg1	response					1400:1407	cellular response	1391:1407	cellular response	1391:1407	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	1	37	theme	drugs	203:207	arg1	efficacy					181:188	the efficacy	177:188	the efficacy of antitumor drugs	177:207	Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment.
30884134	0	38	theme	proteomic	20:28	arg1	alterations					30:40	proteomic alterations	20:40	proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line	20:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	1	39	theme	cancer	285:290	arg1	treatment					292:300	cancer treatment	285:300	cancer treatment	285:300	Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment.
30884134	6	40	theme	response	1400:1407	arg1	conversion					1377:1386	the conversion	1373:1386	the conversion of cellular response	1373:1407	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	6	41	theme	related	1217:1223	arg1	proteins					1208:1215	proteins	1208:1215	proteins related to ER stress	1208:1236	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	6	42	theme	altered	1173:1179	arg1	proteins					1181:1188	these altered proteins	1167:1188	these altered proteins	1167:1188	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	0	43	theme	cell	129:132	arg1	line					134:137	a drug-resistant ovarian carcinoma cell line	94:137	a drug-resistant ovarian carcinoma cell line	94:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	3	44	theme	N-glycosylation	576:590	arg1	inhibition					592:601	N-glycosylation inhibition	576:601	N-glycosylation inhibition	576:601	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	7	45	theme	important	1485:1493	arg1	information					1495:1505	important information	1485:1505	important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment	1485:1618	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	0	46	from	inhibition	80:89	arg1	line					134:137	a drug-resistant ovarian carcinoma cell line	94:137	a drug-resistant ovarian carcinoma cell line	94:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	7	47	theme	dynamic	1440:1446	arg1	data					1457:1460	The dynamic proteome data	1436:1460	The dynamic proteome data presented here	1436:1475	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	2	48	theme	unfolded	383:390	arg1	response					400:407	the unfolded protein response	379:407	the unfolded protein response (UPR)	379:413	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	2	48	theme	unfolded	383:390	arg1	UPR					410:412	UPR	410:412	UPR	410:412	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	7	49	theme	better	1511:1516	arg1	understanding					1518:1530	better understanding	1511:1530	better understanding of the significance of N-glycosylation to cell survival	1511:1586	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	0	50	theme	alterations	30:40	arg1	analysis					8:15	Dynamic analysis	0:15	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.	0:138	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	5	51	theme	proteins	1132:1139	arg1	scale					1123:1127	an extended scale	1111:1127	an extended scale of proteins	1111:1139	The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins.
30884134	5	52	theme	glycosylated	1073:1084	arg1	proteins					1086:1093	glycosylated proteins	1073:1093	glycosylated proteins	1073:1093	The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins.
30884134	4	53	theme	ovarian	941:947	arg1	cells					969:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	3	54	theme	different	653:661	arg1	stages					663:668	different stages	653:668	different stages of N-glycosylation inhibition	653:698	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	4	55	theme	published	872:880	arg1	data					906:909	our previously published quantitative proteomics data	857:909	our previously published quantitative proteomics data	857:909	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	6	56	theme	proteins	1181:1188	arg1	annotation					1153:1162	Functional annotation	1142:1162	Functional annotation of these altered proteins	1142:1188	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	4	57	theme	-treated	932:939	arg1	cells					969:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells	916:973	In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells.
30884134	7	58	theme	TM-related	1592:1601	arg1	treatment					1610:1618	TM-related cancer treatment	1592:1618	TM-related cancer treatment	1592:1618	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	6	59	theme	ER	1309:1310	arg1	apoptosis					1327:1335	ER stress-related apoptosis	1309:1335	ER stress-related apoptosis	1309:1335	Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative.
30884134	7	60	theme	cancer	1603:1608	arg1	treatment					1610:1618	TM-related cancer treatment	1592:1618	TM-related cancer treatment	1592:1618	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
30884134	0	61	link	N-linked	57:64	arg1	inhibition					80:89	N-linked glycosylation inhibition	57:89	N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line	57:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	2	62	theme	reticulum	353:361	arg1	stress					368:373	endoplasmic reticulum (ER) stress	341:373	endoplasmic reticulum (ER) stress	341:373	Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis.
30884134	3	63	theme	expression	542:551	arg1	alterations					553:563	protein expression alterations	534:563	protein expression alterations	534:563	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	3	64	theme	N-glycosylation	673:687	arg1	inhibition					689:698	N-glycosylation inhibition	673:698	N-glycosylation inhibition	673:698	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	1	65	theme	Glycosylation	140:152	arg1	inhibition					154:163	Glycosylation inhibition	140:163	Glycosylation inhibition	140:163	Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment.
30884134	1	66	theme	cancer	238:243	arg1	cells					245:249	cancer cells	238:249	cancer cells	238:249	Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment.
30884134	0	67	theme	glycosylation	66:78	arg1	inhibition					80:89	N-linked glycosylation inhibition	57:89	N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line	57:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	3	68	theme	inhibition	689:698	arg1	stages					663:668	different stages	653:668	different stages of N-glycosylation inhibition	653:698	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	3	69	theme	responses	520:528	arg1	timeline					497:504	the detailed timeline	484:504	the detailed timeline of these cell responses	484:528	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	3	69	theme	responses	520:528	arg1	alterations					553:563	protein expression alterations	534:563	protein expression alterations	534:563	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	3	69	theme	responses	520:528	arg1	explicit					610:617	explicit	610:617	explicit	610:617	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	3	70	theme	detailed	488:495	arg1	timeline					497:504	the detailed timeline	484:504	the detailed timeline of these cell responses	484:528	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	3	70	theme	detailed	488:495	arg1	explicit					610:617	explicit	610:617	explicit	610:617	Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized.
30884134	1	71	theme	cells	245:249	arg1	apoptosis					225:233	the apoptosis	221:233	the apoptosis of cancer cells	221:249	Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment.
30884134	0	72	theme	N-linked	57:64	arg1	inhibition					80:89	N-linked glycosylation inhibition	57:89	N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line	57:137	Dynamic analysis of proteomic alterations in response to N-linked glycosylation inhibition in a drug-resistant ovarian carcinoma cell line.
30884134	5	73	gly	glycosylated	1073:1084	arg1	proteins					1086:1093	glycosylated proteins	1073:1093	glycosylated proteins	1073:1093	The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins.
30884134	7	74	theme	proteome	1448:1455	arg1	data					1457:1460	The dynamic proteome data	1436:1460	The dynamic proteome data presented here	1436:1475	The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.
28871230	10	0	theme	MALDI-TOF/TOF-MS	2000:2015	arg1	results					2017:2023	The MALDI-TOF/TOF-MS results	1996:2023	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	1996:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	2	1	theme	healthy	786:792	arg1	volunteers					794:803	healthy volunteers	786:803	healthy volunteers (HV, n = 35)	786:816	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	1	2	from	carcinoma	288:296	arg1	humans					301:306	humans	301:306	humans	301:306	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	3	theme	chronic	218:224	arg1	Background					141:150	Background	141:150	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.	141:525	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	3	theme	chronic	218:224	arg1	infection					161:169	Chronic infection	153:169	Chronic infection with HBV (CHB) or HCV (CHC)	153:197	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	3	theme	chronic	218:224	arg1	hepatitis					232:240	the most common chronic viral hepatitis	202:240	the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients	202:524	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	8	4	theme	individual	1646:1655	arg1	analysis					1657:1664	The individual analysis	1642:1664	The individual analysis	1642:1664	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	3	5	theme	expression	883:892	arg1	levels					894:899	the expression levels	879:899	the expression levels of their serum glycopatterns	879:928	Lectin blotting was further utilized to validate and assess the expression levels of their serum glycopatterns.
28871230	10	6	link	N-linked	2028:2035	arg1	glycans					2037:2043	N-linked glycans	2028:2043	N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	2028:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	9	7	theme	N-glycans	1875:1883	arg1	PHA-E+L					1892:1898	a complex-type N-glycans binder PHA-E+L	1860:1898	a complex-type N-glycans binder PHA-E+L	1860:1898	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	5	8	theme	serum	1272:1276	arg1	glycopatterns					1286:1298	serum protein glycopatterns	1272:1298	serum protein glycopatterns	1272:1298	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	10	9	dep	m/z	2275:2277	arg1	e.g.					2269:2272	e.g.	2269:2272	e.g.	2269:2272	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	2	10	theme	lectin	559:564	arg1	microarrays					566:576	the lectin microarrays	555:576	the lectin microarrays	555:576	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	1	11	theme	glycopatterns	424:436	arg1	difference					397:406	the difference	393:406	the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients	393:524	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	6	12	theme	expression	1373:1382	arg1	levels					1384:1389	significantly decreased expression levels	1349:1389	significantly decreased expression levels	1349:1389	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	3	13	theme	serum	910:914	arg1	glycopatterns					916:928	their serum glycopatterns	904:928	their serum glycopatterns	904:928	Lectin blotting was further utilized to validate and assess the expression levels of their serum glycopatterns.
28871230	2	14	with	patients	739:746	arg1	n					758:758	n = 54	758:763	n = 54	758:763	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	14	with	patients	739:746	arg1	CHB					753:755	CHB	753:755	CHB (n = 54)	753:764	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	14	with	patients	739:746	arg1	CHC					769:771	CHC	769:771	CHC	769:771	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	5	15	theme	decreased	1241:1249	arg1	levels					1262:1267	significantly decreased expression levels	1227:1267	significantly decreased expression levels of serum protein glycopatterns	1227:1298	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	4	16	theme	glycoprotein	963:974	arg1	glycopatterns					976:988	the glycoprotein glycopatterns	959:988	the glycoprotein glycopatterns	959:988	Finally, the differences of the glycoprotein glycopatterns were systematically compared between CHB and CHC patients.
28871230	0	17	theme	C-Infected	120:129	arg1	Patients					131:138	Chronic Hepatitis B- and C-Infected Patients	95:138	Patients	131:138	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	10	18	theme	particle	2103:2110	arg1	conjugates					2112:2121	PHA-E+L-magnetic particle conjugates	2086:2121	PHA-E+L-magnetic particle conjugates	2086:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	19	theme	glycan	2385:2390	arg1	peaks					2392:2396	3 glycan peaks	2383:2396	3 glycan peaks (1460.659, 2069.740, and 2174.772)	2383:2431	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	7	20	theme	increasing	1574:1583	arg1	trend					1585:1589	a coincidentally increasing trend	1557:1589	a coincidentally increasing trend in both CHC and CHB patients	1557:1618	Furthermore, LEL and MAL-I showed a coincidentally increasing trend in both CHC and CHB patients compared with the HV.
28871230	0	21	from	B-	113:114	arg1	Sera					85:88	Sera	85:88	Sera from Chronic Hepatitis B- and C-Infected Patients	85:138	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	21	from	B-	113:114	arg1	Glycopatterns					25:37	Glycopatterns	25:37	Glycopatterns	25:37	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	21	from	B-	113:114	arg1	N-Glycans					56:64	Complex-Type N-Glycans	43:64	Complex-Type N-Glycans	43:64	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	10	22	gly	glycoproteins	2060:2072	arg1	glycoproteins					2060:2072	the serum glycoproteins	2050:2072	the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	2050:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	2	23	theme	protein	677:683	arg1	glycopatterns					685:697	serum protein glycopatterns	671:697	serum protein glycopatterns	671:697	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	9	24	theme	CHC	1971:1973	arg1	p					1985:1985	p < 0.01	1985:1992	p < 0.01	1985:1992	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	9	24	theme	CHC	1971:1973	arg1	subjects					1975:1982	CHC subjects	1971:1982	CHC subjects (p < 0.01)	1971:1993	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	0	25	theme	Glycoprotein	69:80	arg1	Glycopatterns					25:37	Glycopatterns	25:37	Glycopatterns	25:37	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	25	theme	Glycoprotein	69:80	arg1	N-Glycans					56:64	Complex-Type N-Glycans	43:64	Complex-Type N-Glycans	43:64	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	1	26	theme	Chronic	153:159	arg1	Background					141:150	Background	141:150	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.	141:525	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	26	theme	Chronic	153:159	arg1	infection					161:169	Chronic infection	153:169	Chronic infection with HBV (CHB) or HCV (CHC)	153:197	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	26	theme	Chronic	153:159	arg1	hepatitis					232:240	the most common chronic viral hepatitis	202:240	the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients	202:524	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	5	27	theme	CHB	1312:1314	arg1	patients					1316:1323	the CHB patients	1308:1323	the CHB patients	1308:1323	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	6	28	theme	glycopatterns	1483:1495	arg1	levels					1467:1472	significantly increased expression levels	1432:1472	significantly increased expression levels of serum glycopatterns	1432:1495	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	2	29	theme	letin-mediated	579:592	arg1	glycoproteins					611:623	letin-mediated affinity capture glycoproteins	579:623	letin-mediated affinity capture glycoproteins	579:623	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	11	30	theme	useful	2486:2491	arg1	information					2493:2503	useful information	2486:2503	useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns	2486:2629	Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
28871230	9	31	theme	<	1987:1987	arg1	p					1985:1985	p < 0.01	1985:1992	p < 0.01	1985:1992	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	9	31	theme	<	1987:1987	arg1	subjects					1975:1982	CHC subjects	1971:1982	CHC subjects (p < 0.01)	1971:1993	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	0	32	theme	Chronic	95:101	arg1	B-					113:114	Chronic Hepatitis B- and C-Infected Patients	95:138	B-	113:114	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	4	33	gly	glycoprotein	963:974	arg1	glycoprotein					963:974	the glycoprotein glycopatterns	959:988	the glycoprotein glycopatterns	959:988	Finally, the differences of the glycoprotein glycopatterns were systematically compared between CHB and CHC patients.
28871230	11	34	theme	precision	2581:2589	arg1	alteration					2591:2600	the precision alteration	2577:2600	the precision alteration of their serum glycopatterns	2577:2629	Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
28871230	1	35	theme	-infected	507:515	arg1	patients					517:524	hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients	455:524	hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients	455:524	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	8	36	dep	lectins	1690:1696	arg1	LEL					1731:1733	LEL	1731:1733	LEL	1731:1733	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	lectins					1690:1696	eight lectins	1684:1696	eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I)	1684:1750	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	VVA					1736:1738	VVA	1736:1738	VVA	1736:1738	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	MPL					1699:1701	MPL	1699:1701	MPL	1699:1701	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	UEA-I					1719:1723	UEA-I	1719:1723	UEA-I	1719:1723	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	WGA					1726:1728	WGA	1726:1728	WGA	1726:1728	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	MAL-I					1745:1749	MAL-I	1745:1749	MAL-I	1745:1749	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	GSL-I					1704:1708	GSL-I	1704:1708	GSL-I	1704:1708	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	8	36	dep	lectins	1690:1696	arg1	PTL-II					1711:1716	PTL-II	1711:1716	PTL-II	1711:1716	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	0	37	from	N-Glycans	56:64	arg1	Sera					85:88	Sera	85:88	Sera from Chronic Hepatitis B- and C-Infected Patients	85:138	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	37	from	N-Glycans	56:64	arg1	B-					113:114	Chronic Hepatitis B- and C-Infected Patients	95:138	B-	113:114	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	37	from	N-Glycans	56:64	arg1	Patients					131:138	Chronic Hepatitis B- and C-Infected Patients	95:138	Patients	131:138	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	5	38	theme	glycopatterns	1286:1298	arg1	levels					1262:1267	significantly decreased expression levels	1227:1267	significantly decreased expression levels of serum protein glycopatterns	1227:1298	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	1	39	theme	C	494:494	arg1	virus					496:500	hepatitis C virus	484:500	hepatitis C virus (HCV)	484:506	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	39	theme	C	494:494	arg1	HCV					503:505	HCV	503:505	HCV	503:505	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	8	40	theme	high	1764:1767	arg1	degree					1769:1774	a high degree	1762:1774	a high degree of consistency	1762:1789	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	1	41	theme	distinct	331:338	arg1	processes					351:359	distinct pathogenic processes	331:359	distinct pathogenic processes	331:359	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	8	42	theme	serum	1807:1811	arg1	samples					1813:1819	the pooled serum samples	1796:1819	the pooled serum samples of HV, CHB, and CHC patients	1796:1848	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	6	43	theme	expression	1456:1465	arg1	levels					1467:1472	significantly increased expression levels	1432:1472	significantly increased expression levels of serum glycopatterns	1432:1495	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	8	44	theme	HV	1824:1825	arg1	samples					1813:1819	the pooled serum samples	1796:1819	the pooled serum samples of HV, CHB, and CHC patients	1796:1848	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	11	45	theme	new	2513:2515	arg1	biomarkers					2517:2526	new biomarkers	2513:2526	new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns	2513:2629	Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
28871230	9	46	theme	binder	1885:1890	arg1	PHA-E+L					1892:1898	a complex-type N-glycans binder PHA-E+L	1860:1898	a complex-type N-glycans binder PHA-E+L	1860:1898	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	0	47	theme	Comparative	0:10	arg1	Analysis					12:19	Comparative Analysis	0:19	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.	0:139	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	11	48	theme	serum	2611:2615	arg1	glycopatterns					2617:2629	their serum glycopatterns	2605:2629	their serum glycopatterns	2605:2629	Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
28871230	10	49	theme	glycans	2037:2043	arg1	results					2017:2023	The MALDI-TOF/TOF-MS results	1996:2023	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	1996:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	8	50	theme	CHB	1828:1830	arg1	samples					1813:1819	the pooled serum samples	1796:1819	the pooled serum samples of HV, CHB, and CHC patients	1796:1848	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	10	51	theme	N-glycan	2162:2169	arg1	peaks					2171:2175	23 N-glycan peaks	2159:2175	23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581)	2159:2220	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	2	52	theme	capture	603:609	arg1	glycoproteins					611:623	letin-mediated affinity capture glycoproteins	579:623	letin-mediated affinity capture glycoproteins	579:623	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	5	53	theme	increased	1150:1158	arg1	levels					1171:1176	significantly increased expression levels	1136:1176	significantly increased expression levels	1136:1176	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	10	54	dep	was	2141:2143	arg1	an					2145:2146	an	2145:2146	an	2145:2146	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	54	dep	was	2141:2143	arg1	overlap					2148:2154	overlap	2148:2154	was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB	2141:2232	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	1	55	dep	humans	301:306	arg1	have					326:329	have	326:329	have	326:329	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	8	56	theme	pooled	1800:1805	arg1	samples					1813:1819	the pooled serum samples	1796:1819	the pooled serum samples of HV, CHB, and CHC patients	1796:1848	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	2	57	with	volunteers	794:803	arg1	n					758:758	n = 54	758:763	n = 54	758:763	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	57	with	volunteers	794:803	arg1	CHB					753:755	CHB	753:755	CHB (n = 54)	753:764	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	57	with	volunteers	794:803	arg1	CHC					769:771	CHC	769:771	CHC	769:771	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	8	58	theme	patients	1841:1848	arg1	samples					1813:1819	the pooled serum samples	1796:1819	the pooled serum samples of HV, CHB, and CHC patients	1796:1848	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	10	59	from	results	2017:2023	arg1	glycoproteins					2060:2072	the serum glycoproteins	2050:2072	the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	2050:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	1	60	theme	B	465:465	arg1	virus					467:471	hepatitis B virus	455:471	hepatitis B virus	455:471	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	60	theme	B	465:465	arg1	HBV					474:476	HBV	474:476	HBV	474:476	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	61	theme	hepatocellular	273:286	arg1	carcinoma					288:296	hepatocellular carcinoma	273:296	hepatocellular carcinoma	273:296	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	2	62	theme	=	760:760	arg1	n					758:758	n = 54	758:763	n = 54	758:763	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	62	theme	=	760:760	arg1	CHB					753:755	CHB	753:755	CHB (n = 54)	753:764	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	10	63	theme	CHC	2455:2457	arg1	patients					2459:2466	CHC patients	2455:2466	CHC patients	2455:2466	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	64	theme	hepatitis	2346:2354	arg1	patients					2356:2363	virus-infected hepatitis patients	2331:2363	virus-infected hepatitis patients	2331:2363	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	2	65	theme	=	775:775	arg1	patients					739:746	patients	739:746	patients with CHB (n = 54) or CHC(n = 47)	739:779	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	65	theme	=	775:775	arg1	n					773:773	n = 47	773:778	n = 47	773:778	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	3	66	used	utilized	847:854	arg2	blotting					826:833	Lectin blotting	819:833	Lectin blotting	819:833	Lectin blotting was further utilized to validate and assess the expression levels of their serum glycopatterns.
28871230	10	67	located	observed	2438:2445	arg2	peaks					2392:2396	3 glycan peaks	2383:2396	3 glycan peaks (1460.659, 2069.740, and 2174.772)	2383:2431	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	67	located	observed	2438:2445	arg1	patients					2459:2466	CHC patients	2455:2466	CHC patients	2455:2466	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	1	68	contain	have	326:329	arg2	processes					351:359	distinct pathogenic processes	331:359	distinct pathogenic processes	331:359	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	68	contain	have	326:329	arg1	infections					315:324	their infections	309:324	their infections	309:324	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	69	theme	common	211:216	arg1	Background					141:150	Background	141:150	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.	141:525	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	69	theme	common	211:216	arg1	infection					161:169	Chronic infection	153:169	Chronic infection with HBV (CHB) or HCV (CHC)	153:197	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	69	theme	common	211:216	arg1	hepatitis					232:240	the most common chronic viral hepatitis	202:240	the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients	202:524	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	2	70	from	volunteers	794:803	arg1	structures					723:732	the glycan structures	712:732	the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35)	712:816	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	1	71	from	difference	397:406	arg1	serum					441:445	serum	441:445	serum	441:445	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	9	72	theme	complex-type	1862:1873	arg1	PHA-E+L					1892:1898	a complex-type N-glycans binder PHA-E+L	1860:1898	a complex-type N-glycans binder PHA-E+L	1860:1898	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	1	73	from	cirrhosis	259:267	arg1	humans					301:306	humans	301:306	humans	301:306	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	74	theme	viral	226:230	arg1	Background					141:150	Background	141:150	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.	141:525	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	74	theme	viral	226:230	arg1	infection					161:169	Chronic infection	153:169	Chronic infection with HBV (CHB) or HCV (CHC)	153:197	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	74	theme	viral	226:230	arg1	hepatitis					232:240	the most common chronic viral hepatitis	202:240	the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients	202:524	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	7	75	theme	CHB	1607:1609	arg1	patients					1611:1618	both CHC and CHB patients	1594:1618	both CHC and CHB patients	1594:1618	Furthermore, LEL and MAL-I showed a coincidentally increasing trend in both CHC and CHB patients compared with the HV.
28871230	2	76	theme	glycan	716:721	arg1	structures					723:732	the glycan structures	712:732	the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35)	712:816	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	77	dep	volunteers	794:803	arg1	HV					806:807	HV	806:807	HV	806:807	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	9	78	from	NFIs	1934:1937	arg1	CHB					1946:1948	the CHB	1942:1948	the CHB	1942:1948	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	1	79	theme	glycoprotein	411:422	arg1	glycopatterns					424:436	glycoprotein glycopatterns	411:436	glycoprotein glycopatterns	411:436	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	10	80	theme	N-linked	2028:2035	arg1	glycans					2037:2043	N-linked glycans	2028:2043	N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	2028:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	7	81	theme	CHC	1599:1601	arg1	patients					1611:1618	both CHC and CHB patients	1594:1618	both CHC and CHB patients	1594:1618	Furthermore, LEL and MAL-I showed a coincidentally increasing trend in both CHC and CHB patients compared with the HV.
28871230	2	82	dep	HV	806:807	arg1	n					810:810	n	810:810	n = 35	810:815	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	6	83	theme	decreased	1363:1371	arg1	levels					1384:1389	significantly decreased expression levels	1349:1389	significantly decreased expression levels	1349:1389	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	5	84	dep	HHL	1104:1106	arg1	e.g.					1098:1101	e.g.	1098:1101	e.g.	1098:1101	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	4	85	theme	glycopatterns	976:988	arg1	differences					944:954	the differences	940:954	the differences of the glycoprotein glycopatterns	940:988	Finally, the differences of the glycoprotein glycopatterns were systematically compared between CHB and CHC patients.
28871230	9	86	theme	decreased	1924:1932	arg1	NFIs					1934:1937	significantly decreased NFIs	1910:1937	significantly decreased NFIs in the CHB	1910:1948	Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01).
28871230	5	87	theme	expression	1251:1260	arg1	levels					1262:1267	significantly decreased expression levels	1227:1267	significantly decreased expression levels of serum protein glycopatterns	1227:1298	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	10	88	theme	serum	2054:2058	arg1	glycoproteins					2060:2072	the serum glycoproteins	2050:2072	the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	2050:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	7	89	from	trend	1585:1589	arg1	patients					1611:1618	both CHC and CHB patients	1594:1618	both CHC and CHB patients	1594:1618	Furthermore, LEL and MAL-I showed a coincidentally increasing trend in both CHC and CHB patients compared with the HV.
28871230	5	90	theme	protein	1278:1284	arg1	glycopatterns					1286:1298	serum protein glycopatterns	1272:1298	serum protein glycopatterns	1272:1298	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	10	91	theme	PHA-E+L-magnetic	2086:2101	arg1	conjugates					2112:2121	PHA-E+L-magnetic particle conjugates	2086:2121	PHA-E+L-magnetic particle conjugates	2086:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	6	92	theme	CHC	1509:1511	arg1	patients					1513:1520	the CHC patients	1505:1520	the CHC patients	1505:1520	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	10	93	theme	CHC	2239:2241	arg1	patients					2243:2250	CHC patients	2239:2250	CHC patients	2239:2250	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	93	theme	CHC	2239:2241	arg1	peaks					2262:2266	5 glycan peaks	2253:2266	5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750)	2253:2311	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	4	94	dep	CHB	1027:1029	arg1	patients					1039:1046	patients	1039:1046	patients	1039:1046	Finally, the differences of the glycoprotein glycopatterns were systematically compared between CHB and CHC patients.
28871230	6	95	dep	lectins	1400:1406	arg1	lectins					1400:1406	two lectins	1396:1406	two lectins (WGA and SNA)	1396:1420	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	6	95	dep	lectins	1400:1406	arg1	SNA					1417:1419	SNA	1417:1419	SNA	1417:1419	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	6	95	dep	lectins	1400:1406	arg1	WGA					1409:1411	WGA	1409:1411	WGA	1409:1411	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	1	96	gly	glycoprotein	411:422	arg1	glycoprotein					411:422	glycoprotein glycopatterns	411:436	glycoprotein glycopatterns	411:436	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	0	97	from	Glycopatterns	25:37	arg1	Sera					85:88	Sera	85:88	Sera from Chronic Hepatitis B- and C-Infected Patients	85:138	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	97	from	Glycopatterns	25:37	arg1	B-					113:114	Chronic Hepatitis B- and C-Infected Patients	95:138	B-	113:114	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	97	from	Glycopatterns	25:37	arg1	Patients					131:138	Chronic Hepatitis B- and C-Infected Patients	95:138	Patients	131:138	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	2	98	theme	serum	671:675	arg1	glycopatterns					685:697	serum protein glycopatterns	671:697	serum protein glycopatterns	671:697	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	10	99	theme	glycan	2255:2260	arg1	patients					2243:2250	CHC patients	2239:2250	CHC patients	2239:2250	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	99	theme	glycan	2255:2260	arg1	peaks					2262:2266	5 glycan peaks	2253:2266	5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750)	2253:2311	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	11	100	dep	CHB	2547:2549	arg1	patients					2559:2566	patients	2559:2566	patients	2559:2566	Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
28871230	1	101	with	infection	161:169	arg1	CHB					181:183	CHB	181:183	CHB	181:183	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	101	with	infection	161:169	arg1	HCV					189:191	HCV	189:191	HCV (CHC)	189:197	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	101	with	infection	161:169	arg1	HBV					176:178	HBV	176:178	HBV (CHB)	176:184	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	101	with	infection	161:169	arg1	CHC					194:196	CHC	194:196	CHC	194:196	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	2	102	theme	affinity	594:601	arg1	glycoproteins					611:623	letin-mediated affinity capture glycoproteins	579:623	letin-mediated affinity capture glycoproteins	579:623	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	0	103	theme	Hepatitis	103:111	arg1	B-					113:114	Chronic Hepatitis B- and C-Infected Patients	95:138	B-	113:114	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	3	104	theme	glycopatterns	916:928	arg1	levels					894:899	the expression levels	879:899	the expression levels of their serum glycopatterns	879:928	Lectin blotting was further utilized to validate and assess the expression levels of their serum glycopatterns.
28871230	6	105	theme	serum	1477:1481	arg1	glycopatterns					1483:1495	serum glycopatterns	1477:1495	serum glycopatterns	1477:1495	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	10	106	dep	peaks	2392:2396	arg1	2069.740					2409:2416	2069.740	2409:2416	2069.740	2409:2416	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	106	dep	peaks	2392:2396	arg1	2174.772					2423:2430	2174.772	2423:2430	2174.772	2423:2430	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	1	107	theme	hepatitis	484:492	arg1	virus					496:500	hepatitis C virus	484:500	hepatitis C virus (HCV)	484:506	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	107	theme	hepatitis	484:492	arg1	HCV					503:505	HCV	503:505	HCV	503:505	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	11	108	theme	glycopatterns	2617:2629	arg1	alteration					2591:2600	the precision alteration	2577:2600	the precision alteration of their serum glycopatterns	2577:2629	Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
28871230	8	109	theme	consistency	1779:1789	arg1	degree					1769:1774	a high degree	1762:1774	a high degree of consistency	1762:1789	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	1	110	theme	pathogenic	340:349	arg1	processes					351:359	distinct pathogenic processes	331:359	distinct pathogenic processes	331:359	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	6	111	theme	increased	1446:1454	arg1	levels					1467:1472	significantly increased expression levels	1432:1472	significantly increased expression levels of serum glycopatterns	1432:1495	However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients.
28871230	10	112	dep	1419.743	2188:2195	arg1	e.g.					2178:2181	e.g.	2178:2181	e.g.	2178:2181	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	8	113	theme	CHC	1837:1839	arg1	patients					1841:1848	CHC patients	1837:1848	CHC patients	1837:1848	The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients.
28871230	5	114	theme	expression	1160:1169	arg1	levels					1171:1176	significantly increased expression levels	1136:1176	significantly increased expression levels	1136:1176	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	0	115	theme	Complex-Type	43:54	arg1	N-Glycans					56:64	Complex-Type N-Glycans	43:64	Complex-Type N-Glycans	43:64	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	10	116	theme	m/z	2184:2186	arg1	1419.743					2188:2195	m/z 1419.743	2184:2195	m/z 1419.743	2184:2195	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	117	from	glycoproteins	2060:2072	arg1	results					2017:2023	The MALDI-TOF/TOF-MS results	1996:2023	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	1996:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	10	117	from	glycoproteins	2060:2072	arg1	glycans					2037:2043	N-linked glycans	2028:2043	N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates	2028:2121	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	1	118	theme	hepatitis	455:463	arg1	virus					467:471	hepatitis B virus	455:471	hepatitis B virus	455:471	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	1	118	theme	hepatitis	455:463	arg1	HBV					474:476	HBV	474:476	HBV	474:476	Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients.
28871230	5	119	dep	lectins	1189:1195	arg1	VVA					1203:1205	VVA	1203:1205	VVA	1203:1205	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	5	119	dep	lectins	1189:1195	arg1	ACA					1212:1214	ACA	1212:1214	ACA	1212:1214	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	5	119	dep	lectins	1189:1195	arg1	LCA					1198:1200	LCA	1198:1200	LCA	1198:1200	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	5	119	dep	lectins	1189:1195	arg1	lectins					1189:1195	three lectins	1183:1195	three lectins (LCA, VVA, and ACA)	1183:1215	Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients.
28871230	2	120	theme	=	812:812	arg1	n					810:810	n	810:810	n = 35	810:815	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	3	121	theme	Lectin	819:824	arg1	blotting					826:833	Lectin blotting	819:833	Lectin blotting	819:833	Lectin blotting was further utilized to validate and assess the expression levels of their serum glycopatterns.
28871230	10	122	theme	virus-infected	2331:2344	arg1	patients					2356:2363	virus-infected hepatitis patients	2331:2363	virus-infected hepatitis patients	2331:2363	The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients.
28871230	0	123	from	Patients	131:138	arg1	Sera					85:88	Sera	85:88	Sera from Chronic Hepatitis B- and C-Infected Patients	85:138	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	123	from	Patients	131:138	arg1	Glycopatterns					25:37	Glycopatterns	25:37	Glycopatterns	25:37	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	0	123	from	Patients	131:138	arg1	N-Glycans					56:64	Complex-Type N-Glycans	43:64	Complex-Type N-Glycans	43:64	Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients.
28871230	2	124	dep	=	812:812	arg1	35					814:815	35	814:815	35	814:815	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	125	from	patients	739:746	arg1	structures					723:732	the glycan structures	712:732	the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35)	712:816	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
28871230	2	126	gly	glycoproteins	611:623	arg1	glycoproteins					611:623	letin-mediated affinity capture glycoproteins	579:623	letin-mediated affinity capture glycoproteins	579:623	Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35).
29384693	7	0	theme	74	1134:1135	arg1	kDa					1137:1139	kDa	1137:1139	kDa	1137:1139	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	3	1	theme	fatty	532:536	arg1	palmitate					553:561	palmitate	553:561	palmitate	553:561	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	1	theme	fatty	532:536	arg1	mediators					591:599	proinflammatory mediators	575:599	proinflammatory mediators	575:599	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	1	theme	fatty	532:536	arg1	acids					538:542	select free fatty acids	520:542	select free fatty acids	520:542	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	11	2	theme	human	1698:1702	arg1	muscle					1720:1725	human vascular smooth muscle	1698:1725	human vascular smooth muscle	1698:1725	Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle.
29384693	2	3	theme	COX-2	280:284	arg1	activity					286:293	COX-2 activity	280:293	COX-2 activity	280:293	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	11	4	theme	action	1688:1693	arg1	mechanisms					1674:1683	two separate mechanisms	1661:1683	two separate mechanisms of action in human vascular smooth muscle	1661:1725	Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle.
29384693	9	5	theme	glycosylation	1460:1472	arg1	inhibitor					1474:1482	a glycosylation inhibitor	1458:1482	a glycosylation inhibitor	1458:1482	Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E2 production that was also attenuated by a glycosylation inhibitor.
29384693	12	6	theme	COX-2	1767:1771	arg1	expression					1781:1790	COX-2 protein expression	1767:1790	COX-2 protein expression	1767:1790	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	2	7	theme	prostanoid	305:314	arg1	production					316:325	prostanoid production	305:325	prostanoid production	305:325	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	4	8	theme	COX-2	638:642	arg1	expression					644:653	COX-2 expression	638:653	COX-2 expression	638:653	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	8	9	theme	N-linked	1204:1211	arg1	inhibition					1227:1236	N-linked glycosylation inhibition	1204:1236	N-linked glycosylation inhibition	1204:1236	This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2.
29384693	7	10	theme	COX-2	1067:1071	arg1	levels					1073:1078	COX-2 levels	1067:1078	COX-2 levels	1067:1078	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	2	11	theme	vascular	221:228	arg1	pathologies					230:240	vascular pathologies	221:240	vascular pathologies such as atherosclerosis	221:264	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	2	11	theme	vascular	221:228	arg1	atherosclerosis					250:264	atherosclerosis	250:264	atherosclerosis	250:264	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	5	12	theme	COX-2	813:817	arg1	expression					819:828	COX-2 expression	813:828	COX-2 expression	813:828	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	8	13	theme	activated	1297:1305	arg1	glycoform					1307:1315	the fully activated glycoform	1287:1315	the fully activated glycoform of COX-2	1287:1324	This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2.
29384693	12	14	theme	dose-dependent	1739:1752	arg1	increases					1754:1762	dose-dependent increases	1739:1762	dose-dependent increases in COX-2 protein expression	1739:1790	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	6	15	theme	protein	923:929	arg1	levels					931:936	COX-2 protein levels	917:936	COX-2 protein levels	917:936	Cells were treated with palmitate, COX-2 protein levels were assessed using Western analysis, and activity was assessed via ELISA.
29384693	4	16	theme	vascular	722:729	arg1	inflammation					731:742	vascular inflammation	722:742	vascular inflammation	722:742	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	0	17	theme	vascular	69:76	arg1	cells					92:96	primary human vascular smooth muscle cells	55:96	primary human vascular smooth muscle cells	55:96	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	5	18	from	effect	790:795	arg1	function					834:841	function	834:841	function	834:841	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	5	18	from	effect	790:795	arg1	expression					819:828	COX-2 expression	813:828	COX-2 expression	813:828	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	0	19	theme	muscle	85:90	arg1	cells					92:96	primary human vascular smooth muscle cells	55:96	primary human vascular smooth muscle cells	55:96	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	8	20	gly	glycoform	1307:1315	arg1	COX-2					1320:1324	COX-2	1320:1324	COX-2	1320:1324	This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2.
29384693	2	21	dep	development	349:359	arg1	the					345:347	the	345:347	the	345:347	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	2	22	theme	atherosclerotic	422:436	arg1	plaques					438:444	unstable atherosclerotic plaques	413:444	unstable atherosclerotic plaques	413:444	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	9	23	theme	Palmitate-induced	1327:1343	arg1	increases					1345:1353	Palmitate-induced increases	1327:1353	Palmitate-induced increases in COX-2 levels	1327:1369	Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E2 production that was also attenuated by a glycosylation inhibitor.
29384693	2	24	theme	vascular	380:387	arg1	inflammation					389:400	vascular inflammation	380:400	vascular inflammation leading to unstable atherosclerotic plaques	380:444	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	8	25	link	N-linked	1204:1211	arg1	inhibition					1227:1236	N-linked glycosylation inhibition	1204:1236	N-linked glycosylation inhibition	1204:1236	This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2.
29384693	1	26	theme	Vascular	99:106	arg1	expression					139:148	Vascular basal cyclooxygenase-2 (COX-2) expression	99:148	Vascular basal cyclooxygenase-2 (COX-2) expression	99:148	Vascular basal cyclooxygenase-2 (COX-2) expression and activity can be induced by endotoxin, hypoxia, or ischemia.
29384693	2	27	theme	increased	450:458	arg1	risk					460:463	increased risk	450:463	increased risk for thrombotic events	450:485	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	10	28	theme	increased	1537:1545	arg1	density					1552:1558	increased cell density	1537:1558	increased cell density which were reversed by selective COX-2 inhibition	1537:1608	Additionally, palmitate altered cell morphology and increased cell density which were reversed by selective COX-2 inhibition.
29384693	1	29	theme	cyclooxygenase-2	114:129	arg1	expression					139:148	Vascular basal cyclooxygenase-2 (COX-2) expression	99:148	Vascular basal cyclooxygenase-2 (COX-2) expression	99:148	Vascular basal cyclooxygenase-2 (COX-2) expression and activity can be induced by endotoxin, hypoxia, or ischemia.
29384693	2	30	theme	unstable	413:420	arg1	plaques					438:444	unstable atherosclerotic plaques	413:444	unstable atherosclerotic plaques	413:444	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	0	31	theme	cyclooxygenase-2	35:50	arg1	glycosylation					18:30	glycosylation	18:30	glycosylation of cyclooxygenase-2	18:50	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	7	32	theme	slowest	1147:1153	arg1	band					1165:1168	slowest migrating band	1147:1168	slowest migrating band	1147:1168	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	7	32	theme	slowest	1147:1153	arg1	band					1141:1144	the COX-2 74 kDa band	1124:1144	the COX-2 74 kDa band (slowest migrating band)	1124:1169	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	12	33	theme	glycosylation	1873:1885	arg1	modification					1839:1850	modification	1839:1850	modification of posttranslational glycosylation	1839:1885	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	11	34	from	mechanisms	1674:1683	arg1	muscle					1720:1725	human vascular smooth muscle	1698:1725	human vascular smooth muscle	1698:1725	Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle.
29384693	0	35	theme	primary	55:61	arg1	cells					92:96	primary human vascular smooth muscle cells	55:96	primary human vascular smooth muscle cells	55:96	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	9	36	theme	prostaglandin	1402:1414	arg1	E2					1416:1417	prostaglandin E2	1402:1417	prostaglandin E2 production that was also attenuated by a glycosylation inhibitor	1402:1482	Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E2 production that was also attenuated by a glycosylation inhibitor.
29384693	10	37	theme	COX-2	1593:1597	arg1	inhibition					1599:1608	selective COX-2 inhibition	1583:1608	selective COX-2 inhibition	1583:1608	Additionally, palmitate altered cell morphology and increased cell density which were reversed by selective COX-2 inhibition.
29384693	5	38	theme	smooth	861:866	arg1	cells					875:879	human vascular smooth muscle cells	846:879	human vascular smooth muscle cells	846:879	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	0	39	theme	human	63:67	arg1	cells					92:96	primary human vascular smooth muscle cells	55:96	primary human vascular smooth muscle cells	55:96	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	6	40	theme	COX-2	917:921	arg1	levels					931:936	COX-2 protein levels	917:936	COX-2 protein levels	917:936	Cells were treated with palmitate, COX-2 protein levels were assessed using Western analysis, and activity was assessed via ELISA.
29384693	7	41	theme	COX-2	1128:1132	arg1	band					1165:1168	slowest migrating band	1147:1168	slowest migrating band	1147:1168	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	7	41	theme	COX-2	1128:1132	arg1	band					1141:1144	the COX-2 74 kDa band	1124:1144	the COX-2 74 kDa band (slowest migrating band)	1124:1169	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	3	42	theme	free	527:530	arg1	palmitate					553:561	palmitate	553:561	palmitate	553:561	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	42	theme	free	527:530	arg1	mediators					591:599	proinflammatory mediators	575:599	proinflammatory mediators	575:599	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	42	theme	free	527:530	arg1	acids					538:542	select free fatty acids	520:542	select free fatty acids	520:542	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	11	43	theme	separate	1665:1672	arg1	mechanisms					1674:1683	two separate mechanisms	1661:1683	two separate mechanisms of action in human vascular smooth muscle	1661:1725	Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle.
29384693	4	44	from	impact	677:682	arg1	expression					644:653	COX-2 expression	638:653	COX-2 expression	638:653	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	44	from	impact	677:682	arg1	progression					707:717	progression	707:717	progression	707:717	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	44	from	impact	677:682	arg1	development					691:701	development	691:701	development	691:701	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	44	from	impact	677:682	arg1	activity					659:666	activity	659:666	activity	659:666	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	12	45	theme	COX-2	1820:1824	arg1	activity					1826:1833	COX-2 activity	1820:1833	COX-2 activity	1820:1833	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	11	46	theme	vascular	1704:1711	arg1	muscle					1720:1725	human vascular smooth muscle	1698:1725	human vascular smooth muscle	1698:1725	Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle.
29384693	7	47	theme	band	1106:1109	arg1	intensity					1111:1119	band intensity	1106:1119	band intensity of the COX-2 74 kDa band (slowest migrating band)	1106:1169	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	5	48	theme	vascular	852:859	arg1	cells					875:879	human vascular smooth muscle cells	846:879	human vascular smooth muscle cells	846:879	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	7	49	theme	band	1141:1144	arg1	intensity					1111:1119	band intensity	1106:1119	band intensity of the COX-2 74 kDa band (slowest migrating band)	1106:1169	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	12	50	theme	protein	1773:1779	arg1	expression					1781:1790	COX-2 protein expression	1767:1790	COX-2 protein expression	1767:1790	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	5	51	theme	muscle	868:873	arg1	cells					875:879	human vascular smooth muscle cells	846:879	human vascular smooth muscle cells	846:879	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	9	52	from	increases	1345:1353	arg1	levels					1364:1369	COX-2 levels	1358:1369	COX-2 levels	1358:1369	Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E2 production that was also attenuated by a glycosylation inhibitor.
29384693	3	53	theme	proinflammatory	575:589	arg1	palmitate					553:561	palmitate	553:561	palmitate	553:561	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	53	theme	proinflammatory	575:589	arg1	mediators					591:599	proinflammatory mediators	575:599	proinflammatory mediators	575:599	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	53	theme	proinflammatory	575:589	arg1	acids					538:542	select free fatty acids	520:542	select free fatty acids	520:542	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	6	54	theme	Western	958:964	arg1	analysis					966:973	Western analysis	958:973	Western analysis	958:973	Cells were treated with palmitate, COX-2 protein levels were assessed using Western analysis, and activity was assessed via ELISA.
29384693	12	55	from	increases	1754:1762	arg1	expression					1781:1790	COX-2 protein expression	1767:1790	COX-2 protein expression	1767:1790	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	8	56	theme	glycosylation	1213:1225	arg1	inhibition					1227:1236	N-linked glycosylation inhibition	1204:1236	N-linked glycosylation inhibition	1204:1236	This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2.
29384693	5	57	from	function	834:841	arg1	cells					875:879	human vascular smooth muscle cells	846:879	human vascular smooth muscle cells	846:879	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	2	58	from	increases	267:275	arg1	activity					286:293	COX-2 activity	280:293	COX-2 activity	280:293	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	8	59	theme	glycoform	1307:1315	arg1	expression					1273:1282	expression	1273:1282	expression of the fully activated glycoform of COX-2	1273:1324	This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2.
29384693	0	60	theme	smooth	78:83	arg1	cells					92:96	primary human vascular smooth muscle cells	55:96	primary human vascular smooth muscle cells	55:96	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	8	61	theme	COX-2	1320:1324	arg1	glycoform					1307:1315	the fully activated glycoform	1287:1315	the fully activated glycoform of COX-2	1287:1324	This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2.
29384693	4	62	from	effect	615:620	arg1	expression					644:653	COX-2 expression	638:653	COX-2 expression	638:653	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	62	from	effect	615:620	arg1	progression					707:717	progression	707:717	progression	707:717	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	62	from	effect	615:620	arg1	development					691:701	development	691:701	development	691:701	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	62	from	effect	615:620	arg1	activity					659:666	activity	659:666	activity	659:666	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	9	63	from	increase	1390:1397	arg1	production					1419:1428	prostaglandin E2 production	1402:1428	prostaglandin E2 production that was also attenuated by a glycosylation inhibitor	1402:1482	Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E2 production that was also attenuated by a glycosylation inhibitor.
29384693	4	64	dep	development	691:701	arg1	the					687:689	the	687:689	the	687:689	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	5	65	from	expression	819:828	arg1	cells					875:879	human vascular smooth muscle cells	846:879	human vascular smooth muscle cells	846:879	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	2	66	theme	inflammation	389:400	arg1	development					349:359	development	349:359	development	349:359	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	2	66	theme	inflammation	389:400	arg1	progression					365:375	progression	365:375	progression	365:375	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	5	67	theme	palmitate	800:808	arg1	effect					790:795	the effect	786:795	the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells	786:879	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	4	68	theme	inflammation	731:742	arg1	progression					707:717	progression	707:717	progression	707:717	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	68	theme	inflammation	731:742	arg1	development					691:701	development	691:701	development	691:701	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	7	69	theme	migrating	1155:1163	arg1	band					1165:1168	slowest migrating band	1147:1168	slowest migrating band	1147:1168	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	7	69	theme	migrating	1155:1163	arg1	band					1141:1144	the COX-2 74 kDa band	1124:1144	the COX-2 74 kDa band (slowest migrating band)	1124:1169	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	9	70	theme	COX-2	1358:1362	arg1	levels					1364:1369	COX-2 levels	1358:1369	COX-2 levels	1358:1369	Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E2 production that was also attenuated by a glycosylation inhibitor.
29384693	1	71	theme	basal	108:112	arg1	COX-2					132:136	COX-2	132:136	COX-2	132:136	Vascular basal cyclooxygenase-2 (COX-2) expression and activity can be induced by endotoxin, hypoxia, or ischemia.
29384693	1	71	theme	basal	108:112	arg1	cyclooxygenase-2					114:129	basal cyclooxygenase-2	108:129	Vascular basal cyclooxygenase-2 (COX-2) expression	99:148	Vascular basal cyclooxygenase-2 (COX-2) expression and activity can be induced by endotoxin, hypoxia, or ischemia.
29384693	3	72	theme	Recent	488:493	arg1	studies					495:501	Recent studies	488:501	Recent studies	488:501	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	10	73	theme	cell	1517:1520	arg1	morphology					1522:1531	cell morphology	1517:1531	cell morphology	1517:1531	Additionally, palmitate altered cell morphology and increased cell density which were reversed by selective COX-2 inhibition.
29384693	11	74	theme	smooth	1713:1718	arg1	muscle					1720:1725	human vascular smooth muscle	1698:1725	human vascular smooth muscle	1698:1725	Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle.
29384693	7	75	theme	kDa	1137:1139	arg1	band					1165:1168	slowest migrating band	1147:1168	slowest migrating band	1147:1168	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	7	75	theme	kDa	1137:1139	arg1	band					1141:1144	the COX-2 74 kDa band	1124:1144	the COX-2 74 kDa band (slowest migrating band)	1124:1169	We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band).
29384693	0	76	gly	glycosylation	18:30	arg1	cells					92:96	primary human vascular smooth muscle cells	55:96	primary human vascular smooth muscle cells	55:96	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	0	76	gly	glycosylation	18:30	arg1	cyclooxygenase-2					35:50	cyclooxygenase-2	35:50	cyclooxygenase-2	35:50	Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells.
29384693	12	77	theme	posttranslational	1855:1871	arg1	glycosylation					1873:1885	posttranslational glycosylation	1855:1885	posttranslational glycosylation	1855:1885	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	2	78	theme	thrombotic	469:478	arg1	events					480:485	thrombotic events	469:485	thrombotic events	469:485	During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events.
29384693	3	79	theme	select	520:525	arg1	palmitate					553:561	palmitate	553:561	palmitate	553:561	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	79	theme	select	520:525	arg1	mediators					591:599	proinflammatory mediators	575:599	proinflammatory mediators	575:599	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	3	79	theme	select	520:525	arg1	acids					538:542	select free fatty acids	520:542	select free fatty acids	520:542	Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators.
29384693	10	80	theme	cell	1547:1550	arg1	density					1552:1558	increased cell density	1537:1558	increased cell density which were reversed by selective COX-2 inhibition	1537:1608	Additionally, palmitate altered cell morphology and increased cell density which were reversed by selective COX-2 inhibition.
29384693	9	81	theme	E2	1416:1417	arg1	production					1419:1428	prostaglandin E2 production	1402:1428	prostaglandin E2 production that was also attenuated by a glycosylation inhibitor	1402:1482	Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E2 production that was also attenuated by a glycosylation inhibitor.
29384693	5	82	theme	human	846:850	arg1	cells					875:879	human vascular smooth muscle cells	846:879	human vascular smooth muscle cells	846:879	We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells.
29384693	12	83	theme	activity	1826:1833	arg1	regulation					1806:1815	regulation	1806:1815	regulation of COX-2 activity	1806:1833	It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
29384693	4	84	theme	palmitate	625:633	arg1	effect					615:620	the effect	611:620	the effect of palmitate on COX-2 expression and activity	611:666	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	4	84	theme	palmitate	625:633	arg1	impact					677:682	its impact	673:682	its impact on the development and progression of vascular inflammation	673:742	However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated.
29384693	10	85	theme	selective	1583:1591	arg1	inhibition					1599:1608	selective COX-2 inhibition	1583:1608	selective COX-2 inhibition	1583:1608	Additionally, palmitate altered cell morphology and increased cell density which were reversed by selective COX-2 inhibition.
29246839	8	0	from	Variations	1401:1410	arg1	concentrations					1488:1501	the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations	1415:1501	concentrations	1488:1501	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	8	0	from	Variations	1401:1410	arg1	100-800 g/l					1428:1438	100-800 g/l	1428:1438	100-800 g/l	1428:1438	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	8	0	from	Variations	1401:1410	arg1	sucrose					1419:1425	the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations	1415:1501	sucrose	1419:1425	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	4	1	theme	PGFT6x-308	874:883	arg1	productivity					838:849	The volumetric productivity	823:849	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h)	823:917	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h.
29246839	6	2	theme	Endo	1104:1107	arg1	treatment					1112:1120	Endo Hf treatment	1104:1120	Endo Hf treatment	1104:1120	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	2	3	theme	cell	509:512	arg1	toxicity					514:521	cell toxicity	509:521	cell toxicity	509:521	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	8	4	theme	1.5-15	1452:1457	arg1	units					1459:1463	1.5-15 units	1452:1463	1.5-15 units per gram of substrate	1452:1485	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	4	5	theme	clone	868:872	arg1	PGFT6x-308					874:883	the nine-copy clone PGFT6x-308	854:883	the nine-copy clone PGFT6x-308	854:883	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h.
29246839	2	6	theme	7.9-fold	442:449	arg1	yield					487:491	7.9-fold the recombinant enzyme (Sa1-SSTrec) yield	442:491	7.9-fold the recombinant enzyme (Sa1-SSTrec) yield	442:491	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	6	7	contain	had	1157:1159	arg2	effect					1164:1169	no effect	1161:1169	no effect	1161:1169	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	6	7	contain	had	1157:1159	arg1	removal					1064:1070	The removal	1060:1070	The removal of N-linked oligosaccharides by Endo Hf treatment	1060:1120	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	9	8	theme	industrial	1592:1601	arg1	production					1603:1612	the industrial production	1588:1612	the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose	1588:1679	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	6	9	link	N-linked	1075:1082	arg1	oligosaccharides					1084:1099	N-linked oligosaccharides	1075:1099	N-linked oligosaccharides	1075:1099	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	1	10	from	fescue	337:342	arg1	1-fructosyltransferase					283:304	sucrose 1-fructosyltransferase	275:304	sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus)	275:369	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	4	11	theme	volumetric	827:836	arg1	productivity					838:849	The volumetric productivity	823:849	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h)	823:917	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h.
29246839	3	12	theme	signal	582:587	arg1	peptide					589:595	the Saccharomyces cerevisiae α-factor signal peptide	544:595	the Saccharomyces cerevisiae α-factor signal peptide	544:595	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	0	13	theme	high	129:132	arg1	levels					134:139	high levels	129:139	high levels	129:139	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.
29246839	6	14	theme	substrate	1178:1186	arg1	specificities					1200:1212	the substrate and product specificities	1174:1212	the substrate and product specificities	1174:1212	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	2	15	from	increase	376:383	arg1	copies					426:431	one to nine copies	414:431	one to nine copies	414:431	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	5	16	theme	culture	966:972	arg1	supernatant					974:984	the culture supernatant	962:984	the culture supernatant	962:984	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	7	17	theme	total	1356:1360	arg1	carbohydrates					1362:1374	the total carbohydrates	1352:1374	the total carbohydrates	1352:1374	Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF2) and nystose (GF3) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture.
29246839	0	18	theme	Pichia	144:149	arg1	pastoris					151:158	Pichia pastoris	144:158	Pichia pastoris	144:158	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.
29246839	9	19	theme	short-chain	1617:1627	arg1	fructooligosaccharides					1629:1650	short-chain fructooligosaccharides	1617:1650	short-chain fructooligosaccharides	1617:1650	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	1	20	theme	mature	250:255	arg1	region					257:262	the mature region	246:262	the mature region of sucrose	246:273	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	6	21	theme	oligosaccharides	1084:1099	arg1	removal					1064:1070	The removal	1060:1070	The removal of N-linked oligosaccharides by Endo Hf treatment	1060:1120	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	9	22	dep	fructooligosaccharides	1629:1650	arg1	1-kestose					1671:1679	1-kestose	1671:1679	1-kestose	1671:1679	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	1	23	dep	fescue	337:342	arg1	arundinaceus					357:368	Schedonorus arundinaceus	345:368	Schedonorus arundinaceus	345:368	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	8	24	dep	concentrations	1488:1501	arg1	units					1459:1463	1.5-15 units	1452:1463	1.5-15 units per gram of substrate	1452:1485	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	3	25	theme	α-factor	573:580	arg1	peptide					589:595	the Saccharomyces cerevisiae α-factor signal peptide	544:595	the Saccharomyces cerevisiae α-factor signal peptide	544:595	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	6	26	theme	N-linked	1075:1082	arg1	oligosaccharides					1084:1099	N-linked oligosaccharides	1075:1099	N-linked oligosaccharides	1075:1099	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	3	27	theme	dry	751:753	arg1	weight					755:760	dry weight	751:760	dry weight	751:760	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	27	theme	dry	751:753	arg1	106 g/l					742:748	106 g/l	742:748	106 g/l	742:748	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	4	28	theme	nine-copy	858:866	arg1	PGFT6x-308					874:883	the nine-copy clone PGFT6x-308	854:883	the nine-copy clone PGFT6x-308	854:883	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h.
29246839	3	29	theme	periplasmic	609:619	arg1	%					634:634	38%	632:634	38%	632:634	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	29	theme	periplasmic	609:619	arg1	retention					621:629	periplasmic retention	609:629	periplasmic retention (38%)	609:635	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	0	30	theme	Fructooligosaccharides	0:21	arg1	production					23:32	Fructooligosaccharides production	0:32	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase	0:99	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.
29246839	7	31	theme	reaction	1383:1390	arg1	mixture					1392:1398	the reaction mixture	1379:1398	the reaction mixture	1379:1398	Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF2) and nystose (GF3) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture.
29246839	9	32	theme	candidate	1567:1575	arg1	enzyme					1577:1582	an attractive candidate enzyme	1553:1582	an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose	1553:1679	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	9	32	theme	candidate	1567:1575	arg1	Sa1-SSTrec					1539:1548	Sa1-SSTrec	1539:1548	Sa1-SSTrec	1539:1548	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	7	33	theme	carbohydrates	1362:1374	arg1	carbohydrates					1362:1374	the total carbohydrates	1352:1374	the total carbohydrates	1352:1374	Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF2) and nystose (GF3) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture.
29246839	7	33	theme	carbohydrates	1362:1374	arg1	w/w					1344:1346	w/w	1344:1346	w/w	1344:1346	Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF2) and nystose (GF3) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture.
29246839	7	33	theme	carbohydrates	1362:1374	arg1	%					1341:1341	55-60%	1336:1341	55-60% (w/w) of the total carbohydrates	1336:1374	Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF2) and nystose (GF3) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture.
29246839	5	34	from	pH	1035:1036	arg1	active					1025:1030	active	1025:1030	active	1025:1030	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	7	35	theme	ratio	1298:1302	arg1	9:1					1304:1306	a ratio 9:1	1296:1306	a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture	1296:1398	Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF2) and nystose (GF3) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture.
29246839	0	36	theme	Schedonorus	37:47	arg1	1-fructosyltransferase					78:99	Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase	37:99	Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase	37:99	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.
29246839	3	37	theme	cane	795:798	arg1	sugar					800:804	cane sugar	795:804	cane sugar for cell growth	795:820	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	5	38	from	45-50 °C	1050:1057	arg1	active					1025:1030	active	1025:1030	active	1025:1030	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	9	39	theme	attractive	1556:1565	arg1	enzyme					1577:1582	an attractive candidate enzyme	1553:1582	an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose	1553:1679	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	9	39	theme	attractive	1556:1565	arg1	Sa1-SSTrec					1539:1548	Sa1-SSTrec	1539:1548	Sa1-SSTrec	1539:1548	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	2	40	theme	recombinant	455:465	arg1	Sa1-SSTrec					475:484	Sa1-SSTrec	475:484	Sa1-SSTrec	475:484	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	2	40	theme	recombinant	455:465	arg1	enzyme					467:472	the recombinant enzyme	451:472	7.9-fold the recombinant enzyme (Sa1-SSTrec) yield	442:491	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	9	41	theme	fructooligosaccharides	1629:1650	arg1	production					1603:1612	the industrial production	1588:1612	the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose	1588:1679	Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
29246839	3	42	dep	Saccharomyces	548:560	arg1	cerevisiae					562:571	cerevisiae	562:571	cerevisiae	562:571	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	1	43	theme	yeast	183:187	arg1	pastoris					196:203	The non-saccharolytic yeast Pichia pastoris	161:203	The non-saccharolytic yeast Pichia pastoris	161:203	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	0	44	theme	sucrose	62:68	arg1	1-fructosyltransferase					78:99	Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase	37:99	Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase	37:99	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.
29246839	1	45	theme	Tall	332:335	arg1	fescue					337:342	Tall fescue	332:342	Tall fescue (Schedonorus arundinaceus)	332:369	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	1	46	dep	1-fructosyltransferase	283:304	arg1	1-SST					307:311	1-SST	307:311	1-SST	307:311	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	1	46	dep	1-fructosyltransferase	283:304	arg1	EC					314:315	EC 2.4.1.99	314:324	EC 2.4.1.99	314:324	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	5	47	theme	active	1025:1030	arg1	glycoprotein					1002:1013	a monomeric glycoprotein	990:1013	a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C	990:1057	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	5	47	theme	active	1025:1030	arg1	Sa1-SSTrec					937:946	Sa1-SSTrec	937:946	Sa1-SSTrec purified from the culture supernatant	937:984	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	6	48	theme	product	1192:1198	arg1	specificities					1200:1212	the substrate and product specificities	1174:1212	the substrate and product specificities	1174:1212	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	2	49	theme	enzyme	467:472	arg1	yield					487:491	7.9-fold the recombinant enzyme (Sa1-SSTrec) yield	442:491	7.9-fold the recombinant enzyme (Sa1-SSTrec) yield	442:491	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	8	50	theme	product	1522:1528	arg1	profile					1530:1536	the product profile	1518:1536	the product profile	1518:1536	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	0	51	theme	sucrose	70:76	arg1	1-fructosyltransferase					78:99	Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase	37:99	Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase	37:99	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.
29246839	3	52	dep	reached	733:739	arg1	weight					755:760	dry weight	751:760	dry weight	751:760	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	52	dep	reached	733:739	arg1	106 g/l					742:748	106 g/l	742:748	106 g/l	742:748	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	8	53	theme	substrate	1477:1485	arg1	gram					1469:1472	gram	1469:1472	gram of substrate	1469:1485	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	1	54	dep	engineered	209:218	arg1	1-fructosyltransferase					283:304	sucrose 1-fructosyltransferase	275:304	sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus)	275:369	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	6	55	theme	Hf	1109:1110	arg1	treatment					1112:1120	Endo Hf treatment	1104:1120	Endo Hf treatment	1104:1120	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	5	56	gly	glycoprotein	1002:1013	arg1	glycoprotein					1002:1013	a monomeric glycoprotein	990:1013	a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C	990:1057	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	5	56	gly	glycoprotein	1002:1013	arg1	Sa1-SSTrec					937:946	Sa1-SSTrec	937:946	Sa1-SSTrec purified from the culture supernatant	937:984	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	8	57	theme	enzyme	1444:1449	arg1	concentrations					1488:1501	the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations	1415:1501	concentrations	1488:1501	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	8	58	dep	kept	1503:1506	arg1	unaltered					1508:1516	unaltered	1508:1516	unaltered	1508:1516	Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile.
29246839	1	59	theme	Pichia	189:194	arg1	pastoris					196:203	The non-saccharolytic yeast Pichia pastoris	161:203	The non-saccharolytic yeast Pichia pastoris	161:203	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	6	60	theme	enzyme	1136:1141	arg1	stability					1143:1151	the enzyme stability	1132:1151	the enzyme stability	1132:1151	The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities.
29246839	3	61	theme	fed-batch	766:774	arg1	fermentation					776:787	fed-batch fermentation	766:787	fed-batch fermentation using cane sugar for cell growth	766:820	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	7	62	with	9:1	1304:1306	arg1	sum					1319:1321	their sum	1313:1321	their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture	1313:1398	Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF2) and nystose (GF3) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture.
29246839	3	63	theme	overall	689:695	arg1	activity					697:704	an overall activity	686:704	an overall activity of 102.1 U/ml	686:718	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	0	64	dep	Schedonorus	37:47	arg1	arundinaceus					49:60	arundinaceus	49:60	arundinaceus	49:60	Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.
29246839	1	65	theme	sucrose	267:273	arg1	region					257:262	the mature region	246:262	the mature region of sucrose	246:273	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	4	66	theme	fermentation	899:910	arg1	end					892:894	the end	888:894	the end of fermentation (72 h)	888:917	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h.
29246839	3	67	theme	Sa1-SSTrec	672:681	arg1	%					634:634	38%	632:634	38%	632:634	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	67	theme	Sa1-SSTrec	672:681	arg1	release					655:661	extracellular release	641:661	extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml	641:718	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	67	theme	Sa1-SSTrec	672:681	arg1	%					666:666	62%	664:666	62%	664:666	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	67	theme	Sa1-SSTrec	672:681	arg1	retention					621:629	periplasmic retention	609:629	periplasmic retention (38%)	609:635	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	5	68	theme	monomeric	992:1000	arg1	glycoprotein					1002:1013	a monomeric glycoprotein	990:1013	a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C	990:1057	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	5	68	theme	monomeric	992:1000	arg1	Sa1-SSTrec					937:946	Sa1-SSTrec	937:946	Sa1-SSTrec purified from the culture supernatant	937:984	Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C.
29246839	1	69	theme	non-saccharolytic	165:181	arg1	pastoris					196:203	The non-saccharolytic yeast Pichia pastoris	161:203	The non-saccharolytic yeast Pichia pastoris	161:203	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	3	70	theme	cell	810:813	arg1	growth					815:820	cell growth	810:820	cell growth	810:820	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	4	71	from	end	892:894	arg1	productivity					838:849	The volumetric productivity	823:849	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h)	823:917	The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h.
29246839	2	72	dep	nine	421:424	arg1	to					418:419	to	418:419	to	418:419	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	2	73	from	copies	426:431	arg1	increase					376:383	The increase	372:383	The increase of the transgene dosage from one to nine copies	372:431	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	2	73	from	copies	426:431	arg1	dosage					402:407	the transgene dosage	388:407	the transgene dosage from one to nine copies	388:431	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	2	74	theme	dosage	402:407	arg1	increase					376:383	The increase	372:383	The increase of the transgene dosage from one to nine copies	372:431	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
29246839	3	75	theme	Saccharomyces	548:560	arg1	peptide					589:595	the Saccharomyces cerevisiae α-factor signal peptide	544:595	the Saccharomyces cerevisiae α-factor signal peptide	544:595	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	1	76	theme	sucrose	275:281	arg1	1-fructosyltransferase					283:304	sucrose 1-fructosyltransferase	275:304	sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus)	275:369	The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus).
29246839	3	77	theme	102.1 U/ml	709:718	arg1	activity					697:704	an overall activity	686:704	an overall activity of 102.1 U/ml	686:718	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	78	theme	extracellular	641:653	arg1	release					655:661	extracellular release	641:661	extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml	641:718	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	3	78	theme	extracellular	641:653	arg1	%					666:666	62%	664:666	62%	664:666	Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth.
29246839	2	79	theme	transgene	392:400	arg1	dosage					402:407	the transgene dosage	388:407	the transgene dosage from one to nine copies	388:431	The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity.
28939828	6	0	contain	has	1115:1117	arg2	structure					1138:1146	a flexible modular structure	1119:1146	a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements	1119:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	6	0	contain	has	1115:1117	arg1	UGGT					1110:1113	UGGT	1110:1113	UGGT	1110:1113	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	1	1	theme	protein	121:127	arg1	system					145:150	a protein quality control system	119:150	a protein quality control system	119:150	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	7	2	theme	unfolded	1530:1537	arg1	substrates					1539:1548	unfolded substrates	1530:1548	unfolded substrates	1530:1548	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	0	3	theme	enzyme	71:76	arg1	structure					36:44	a flexible modular structure	17:44	a flexible modular structure of the ER folding-sensor enzyme UGGT	17:81	Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.
28939828	1	4	theme	quality	129:135	arg1	system					145:150	a protein quality control system	119:150	a protein quality control system	119:150	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	6	5	theme	cryo-electron	1023:1035	arg1	microscopy					1037:1046	cryo-electron microscopy	1023:1046	cryo-electron microscopy	1023:1046	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	7	6	theme	flexible	1439:1446	arg1	structure					1456:1464	its flexible modular structure	1435:1464	its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates	1435:1548	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	3	7	gly	glycoprotein	372:383	arg1	glycoprotein					372:383	glycoprotein glucosyltransferase	372:403	glycoprotein glucosyltransferase (UGGT)	372:410	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	2	8	theme	glycan	254:259	arg1	intermediates					261:273	N-linked glycan intermediates	245:273	N-linked glycan intermediates displayed on the protein surface	245:306	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	2	9	theme	intermediates	261:273	arg1	tags					325:328	quality tags	317:328	quality tags	317:328	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	2	9	theme	intermediates	261:273	arg1	series					235:240	a series	233:240	a series of N-linked glycan intermediates displayed on the protein surface	233:306	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	3	10	dep	UDP-glucose	360:370	arg1	acts					412:415	acts	412:415	acts	412:415	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	2	11	theme	N-linked	245:252	arg1	intermediates					261:273	N-linked glycan intermediates	245:273	N-linked glycan intermediates displayed on the protein surface	245:306	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	3	12	theme	quality	443:449	arg1	system					459:464	the ER quality control system	436:464	the ER quality control system	436:464	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	5	13	theme	catalytic	907:915	arg1	domain					917:922	the C-terminal catalytic domain	892:922	the C-terminal catalytic domain	892:922	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	7	14	gly	glycoprotein	1403:1414	arg1	glycoprotein					1403:1414	glycoprotein substrates	1403:1425	glycoprotein substrates	1403:1425	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	6	15	theme	flexible	1121:1128	arg1	structure					1138:1146	a flexible modular structure	1119:1146	a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements	1119:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	6	16	theme	folding-sensor	1212:1225	arg1	region					1227:1232	the larger folding-sensor region	1201:1232	the larger folding-sensor region with variable spatial arrangements	1201:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	7	17	theme	substrates	1416:1425	arg1	variety					1392:1398	a variety	1390:1398	a variety of glycoprotein substrates	1390:1425	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	7	17	theme	substrates	1416:1425	arg1	substrates					1416:1425	glycoprotein substrates	1403:1425	glycoprotein substrates	1403:1425	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	1	18	theme	control	137:143	arg1	system					145:150	a protein quality control system	119:150	a protein quality control system	119:150	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	7	19	contain	possessing	1466:1475	arg1	structure					1456:1464	its flexible modular structure	1435:1464	its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates	1435:1548	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	7	19	contain	possessing	1466:1475	arg2	surfaces					1498:1505	extended hydrophobic surfaces	1477:1505	extended hydrophobic surfaces	1477:1505	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	5	20	theme	C-terminal	896:905	arg1	domain					917:922	the C-terminal catalytic domain	892:922	the C-terminal catalytic domain	892:922	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	6	21	theme	smaller	1161:1167	arg1	domain					1179:1184	the smaller catalytic domain	1157:1184	the smaller catalytic domain	1157:1184	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	6	22	theme	atomic	1063:1068	arg1	microscopy					1076:1085	high-speed atomic force microscopy	1052:1085	high-speed atomic force microscopy	1052:1085	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	6	23	theme	modular	1130:1136	arg1	structure					1138:1146	a flexible modular structure	1119:1146	a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements	1119:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	5	24	theme	large	864:868	arg1	cavity					878:883	a large central cavity	862:883	a large central cavity	862:883	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	3	25	theme	enzyme	353:358	arg1	UDP-glucose					360:370	The ER folding-sensor enzyme UDP-glucose	331:370	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.	331:616	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	6	26	with	region	1227:1232	arg1	arrangements					1256:1267	variable spatial arrangements	1239:1267	variable spatial arrangements	1239:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	5	27	theme	thioredoxin-like	758:773	arg1	domains					775:781	four thioredoxin-like domains	753:781	four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity	753:883	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	5	28	theme	ligand-dependent	936:951	arg1	alteration					968:977	a ligand-dependent conformational alteration	934:977	a ligand-dependent conformational alteration	934:977	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	5	29	theme	central	870:876	arg1	cavity					878:883	a large central cavity	862:883	a large central cavity	862:883	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	6	30	theme	X-ray	1005:1009	arg1	scattering					1011:1020	small-angle X-ray scattering	993:1020	small-angle X-ray scattering	993:1020	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	5	31	theme	conformational	953:966	arg1	alteration					968:977	a ligand-dependent conformational alteration	934:977	a ligand-dependent conformational alteration	934:977	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	4	32	theme	enzyme	669:674	arg1	structure					651:659	the dynamic structure	639:659	the dynamic structure of this enzyme	639:674	Here we characterise the dynamic structure of this enzyme.
28939828	3	33	theme	ER	335:336	arg1	UDP-glucose					360:370	The ER folding-sensor enzyme UDP-glucose	331:370	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.	331:616	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	6	34	theme	small-angle	993:1003	arg1	scattering					1011:1020	small-angle X-ray scattering	993:1020	small-angle X-ray scattering	993:1020	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	5	35	with	structure	847:855	arg1	cavity					878:883	a large central cavity	862:883	a large central cavity	862:883	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	7	36	theme	hydrophobic	1486:1496	arg1	surfaces					1498:1505	extended hydrophobic surfaces	1477:1505	extended hydrophobic surfaces	1477:1505	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	1	37	theme	efficient	168:176	arg1	folding					178:184	the efficient folding	164:184	the efficient folding of newly synthesised proteins	164:214	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	3	38	theme	folding-sensor	338:351	arg1	UDP-glucose					360:370	The ER folding-sensor enzyme UDP-glucose	331:370	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.	331:616	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	1	39	theme	endoplasmic	91:101	arg1	ER					114:115	ER	114:115	ER	114:115	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	1	39	theme	endoplasmic	91:101	arg1	reticulum					103:111	the endoplasmic reticulum	87:111	the endoplasmic reticulum (ER)	87:116	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	5	40	theme	C-shaped	838:845	arg1	structure					847:855	a C-shaped structure	836:855	a C-shaped structure with a large central cavity	836:883	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	0	41	theme	structure	36:44	arg1	Visualisation					0:12	Visualisation	0:12	Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.	0:82	Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.
28939828	2	42	link	N-linked	245:252	arg1	intermediates					261:273	N-linked glycan intermediates	245:273	N-linked glycan intermediates displayed on the protein surface	245:306	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	5	43	theme	sensor	724:729	arg1	region					731:736	the sensor region	720:736	the sensor region	720:736	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	7	44	theme	substrates	1539:1548	arg1	recognition					1515:1525	the recognition	1511:1525	the recognition of unfolded substrates	1511:1548	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	0	45	theme	modular	28:34	arg1	structure					36:44	a flexible modular structure	17:44	a flexible modular structure of the ER folding-sensor enzyme UGGT	17:81	Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.
28939828	5	46	theme	β-rich	797:802	arg1	domain					804:809	a β-rich domain	795:809	a β-rich domain	795:809	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	0	47	theme	flexible	19:26	arg1	structure					36:44	a flexible modular structure	17:44	a flexible modular structure of the ER folding-sensor enzyme UGGT	17:81	Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.
28939828	4	48	theme	dynamic	643:649	arg1	structure					651:659	the dynamic structure	639:659	the dynamic structure of this enzyme	639:674	Here we characterise the dynamic structure of this enzyme.
28939828	7	49	theme	structural	1293:1302	arg1	insights					1304:1311	structural insights	1293:1311	structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates	1293:1548	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	7	50	theme	modular	1448:1454	arg1	structure					1456:1464	its flexible modular structure	1435:1464	its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates	1435:1548	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	3	51	from	gatekeeper	422:431	arg1	system					459:464	the ER quality control system	436:464	the ER quality control system	436:464	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	3	52	theme	control	451:457	arg1	system					459:464	the ER quality control system	436:464	the ER quality control system	436:464	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	3	53	theme	glycoprotein	372:383	arg1	gatekeeper					422:431	a gatekeeper	420:431	a gatekeeper in the ER quality control system	420:464	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	3	53	theme	glycoprotein	372:383	arg1	UGGT					406:409	UGGT	406:409	UGGT	406:409	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	3	53	theme	glycoprotein	372:383	arg1	glucosyltransferase					385:403	glycoprotein glucosyltransferase	372:403	glycoprotein glucosyltransferase (UGGT)	372:410	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	5	54	theme	crystallographic	681:696	arg1	data					698:701	Our crystallographic data	677:701	Our crystallographic data	677:701	Our crystallographic data demonstrate that the sensor region is composed of four thioredoxin-like domains followed by a β-rich domain, which are arranged into a C-shaped structure with a large central cavity, while the C-terminal catalytic domain undergoes a ligand-dependent conformational alteration.
28939828	2	55	theme	quality	317:323	arg1	tags					325:328	quality tags	317:328	quality tags	317:328	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	2	55	theme	quality	317:323	arg1	series					235:240	a series	233:240	a series of N-linked glycan intermediates displayed on the protein surface	233:306	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	6	56	theme	catalytic	1169:1177	arg1	domain					1179:1184	the smaller catalytic domain	1157:1184	the smaller catalytic domain	1157:1184	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	7	57	theme	working	1322:1328	arg1	mechanism					1330:1338	the working mechanism	1318:1338	the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates	1318:1548	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	3	58	theme	lectin-chaperone	590:605	arg1	complexes					607:615	lectin-chaperone complexes	590:615	lectin-chaperone complexes	590:615	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	3	59	theme	ER	440:441	arg1	system					459:464	the ER quality control system	436:464	the ER quality control system	436:464	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	1	60	theme	synthesised	195:205	arg1	proteins					207:214	newly synthesised proteins	189:214	newly synthesised proteins	189:214	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	6	61	theme	larger	1205:1210	arg1	region					1227:1232	the larger folding-sensor region	1201:1232	the larger folding-sensor region with variable spatial arrangements	1201:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	3	62	theme	folded	529:534	arg1	glycoproteins					536:548	incompletely folded glycoproteins	516:548	incompletely folded glycoproteins	516:548	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	2	63	theme	protein	292:298	arg1	surface					300:306	the protein surface	288:306	the protein surface	288:306	In this system, a series of N-linked glycan intermediates displayed on the protein surface serve as quality tags.
28939828	1	64	theme	proteins	207:214	arg1	folding					178:184	the efficient folding	164:184	the efficient folding of newly synthesised proteins	164:214	In the endoplasmic reticulum (ER), a protein quality control system facilitates the efficient folding of newly synthesised proteins.
28939828	0	65	theme	folding-sensor	56:69	arg1	enzyme					71:76	the ER folding-sensor enzyme UGGT	49:81	the ER folding-sensor enzyme UGGT	49:81	Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.
28939828	6	66	theme	spatial	1248:1254	arg1	arrangements					1256:1267	variable spatial arrangements	1239:1267	variable spatial arrangements	1239:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	3	67	gly	glycoproteins	536:548	arg1	glycoproteins					536:548	incompletely folded glycoproteins	516:548	incompletely folded glycoproteins	516:548	The ER folding-sensor enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a gatekeeper in the ER quality control system by specifically catalysing monoglucosylation onto incompletely folded glycoproteins, thereby enabling them to interact with lectin-chaperone complexes.
28939828	7	68	theme	glycoprotein	1403:1414	arg1	substrates					1416:1425	glycoprotein substrates	1403:1425	glycoprotein substrates	1403:1425	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
28939828	6	69	theme	high-speed	1052:1061	arg1	microscopy					1076:1085	high-speed atomic force microscopy	1052:1085	high-speed atomic force microscopy	1052:1085	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	0	70	theme	ER	53:54	arg1	enzyme					71:76	the ER folding-sensor enzyme UGGT	49:81	the ER folding-sensor enzyme UGGT	49:81	Visualisation of a flexible modular structure of the ER folding-sensor enzyme UGGT.
28939828	6	71	theme	variable	1239:1246	arg1	arrangements					1256:1267	variable spatial arrangements	1239:1267	variable spatial arrangements	1239:1267	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	6	72	theme	force	1070:1074	arg1	microscopy					1076:1085	high-speed atomic force microscopy	1052:1085	high-speed atomic force microscopy	1052:1085	Furthermore, small-angle X-ray scattering, cryo-electron microscopy and high-speed atomic force microscopy have demonstrated that UGGT has a flexible modular structure in which the smaller catalytic domain is tethered to the larger folding-sensor region with variable spatial arrangements.
28939828	7	73	theme	extended	1477:1484	arg1	surfaces					1498:1505	extended hydrophobic surfaces	1477:1505	extended hydrophobic surfaces	1477:1505	These findings provide structural insights into the working mechanism whereby UGGT operates as a folding-sensor against a variety of glycoprotein substrates through its flexible modular structure possessing extended hydrophobic surfaces for the recognition of unfolded substrates.
31696430	7	0	theme	helix-loop-helix	1229:1244	arg1	structure					1252:1260	a helix-loop-helix (HLH) structure	1227:1260	a helix-loop-helix (HLH) structure	1227:1260	The three-dimensional structure of the 5-HTHdh showed multiple alpha helices which is separated by a helix-loop-helix (HLH) structure.
31696430	3	1	link	N-linked	650:657	arg1	sites					673:677	putative N-linked glycosylation sites	641:677	putative N-linked glycosylation sites	641:677	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	2	theme	consensus	708:716	arg1	motifs					718:723	several phosphorylation consensus motifs	684:723	several phosphorylation consensus motifs	684:723	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	9	3	theme	5-HTHdh	1436:1442	arg1	gene					1444:1447	the 5-HTHdh gene	1432:1447	the 5-HTHdh gene	1432:1447	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	11	4	theme	expressing	1681:1690	arg1	cells					1707:1711	the 5-HTHdh expressing neurosecretory cells	1669:1711	the 5-HTHdh expressing neurosecretory cells	1669:1711	In situ hybridization showed that the 5-HTHdh expressing neurosecretory cells were distributed in the cortex of the pleuropedal ganglion.
31696430	3	5	theme	key	545:547	arg1	sites					673:677	putative N-linked glycosylation sites	641:677	putative N-linked glycosylation sites	641:677	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	5	theme	key	545:547	arg1	domains					632:638	seven hydrophobic transmembrane domains	600:638	seven hydrophobic transmembrane domains	600:638	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	5	theme	key	545:547	arg1	motifs					718:723	several phosphorylation consensus motifs	684:723	several phosphorylation consensus motifs	684:723	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	5	theme	key	545:547	arg1	features					549:556	key features	545:556	key features	545:556	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	6	theme	5-HTHdh	527:533	arg1	profile					516:522	The structural profile	501:522	The structural profile of 5-HTHdh	501:533	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	1	7	theme	Serotonin	167:175	arg1	receptor					177:184	Serotonin receptor	167:184	Serotonin receptor (5-HT)	167:191	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	1	7	theme	Serotonin	167:175	arg1	amine					207:211	a biogenic amine	196:211	a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis	196:323	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	1	7	theme	Serotonin	167:175	arg1	5-HT					187:190	5-HT	187:190	5-HT	187:190	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	4	8	theme	5-HT	860:863	arg1	receptor					865:872	human 5-HT receptor	854:872	human 5-HT receptor	854:872	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	3	9	theme	protein-coupled	563:577	arg1	receptors					579:587	G protein-coupled receptors	561:587	G protein-coupled receptors	561:587	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	5	10	theme	cloned	879:884	arg1	sequence					886:893	The cloned sequence	875:893	The cloned sequence	875:893	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	9	11	located	observed	1454:1461	arg1	ovary					1470:1474	the ovary	1466:1474	the ovary	1466:1474	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	9	11	located	observed	1454:1461	arg2	differences					1385:1395	Significant differences	1373:1395	Significant differences in the transcriptional activity of the 5-HTHdh gene	1373:1447	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	9	11	located	observed	1454:1461	arg1	stage					1492:1496	the ripening stage	1479:1496	the ripening stage	1479:1496	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	10	12	theme	effective	1589:1597	arg1	temperature					1612:1622	higher effective accumulative temperature	1582:1622	higher effective accumulative temperature (1000 °C)	1582:1632	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	12	theme	effective	1589:1597	arg1	1000 °C					1625:1631	1000 °C	1625:1631	1000 °C	1625:1631	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	6	13	with	comparison	1006:1015	arg1	genes					1048:1052	other known 5-HT receptor genes	1022:1052	other known 5-HT receptor genes	1022:1052	Phylogenetic comparison with other known 5-HT receptor genes revealed that the 5-HTHdh is most closely related to the 5-HTHa receptor.
31696430	11	14	dep	In	1635:1636	arg1	situ					1638:1641	situ	1638:1641	situ	1638:1641	In situ hybridization showed that the 5-HTHdh expressing neurosecretory cells were distributed in the cortex of the pleuropedal ganglion.
31696430	0	15	theme	Pacific	126:132	arg1	abalone					134:140	the Pacific abalone	122:140	the Pacific abalone	122:140	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	8	16	theme	receptor	1302:1309	arg1	mRNA					1311:1314	the receptor mRNA	1298:1314	the receptor mRNA	1298:1314	Quantitative PCR demonstrated that the receptor mRNA was predominantly expressed in the pleuropedal ganglion.
31696430	0	17	theme	discus	152:157	arg1	receptor					73:80	a serotonin receptor	61:80	a serotonin receptor involved in the reproductive process of the Pacific abalone	61:140	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	0	17	theme	discus	152:157	arg1	hannai					159:164	Haliotis discus hannai	143:164	Haliotis discus hannai	143:164	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	4	18	from	asinina	821:827	arg1	receptor					798:805	the 5-HT receptor	789:805	the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor	789:872	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	2	19	theme	8.94	495:498	arg1	point					486:490	isoelectric point	474:490	isoelectric point of 8.94	474:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	19	theme	8.94	495:498	arg1	mass					452:455	a predicted molecular mass	430:455	a predicted molecular mass of 46.54 kDa	430:468	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	11	20	theme	pleuropedal	1751:1761	arg1	ganglion					1763:1770	the pleuropedal ganglion	1747:1770	the pleuropedal ganglion	1747:1770	In situ hybridization showed that the 5-HTHdh expressing neurosecretory cells were distributed in the cortex of the pleuropedal ganglion.
31696430	3	21	theme	transmembrane	618:630	arg1	domains					632:638	seven hydrophobic transmembrane domains	600:638	seven hydrophobic transmembrane domains	600:638	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	6	22	theme	Phylogenetic	993:1004	arg1	comparison					1006:1015	Phylogenetic comparison	993:1015	Phylogenetic comparison with other known 5-HT receptor genes	993:1052	Phylogenetic comparison with other known 5-HT receptor genes revealed that the 5-HTHdh is most closely related to the 5-HTHa receptor.
31696430	0	23	theme	receptor	73:80	arg1	characterization					16:31	characterization	16:31	characterization	16:31	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	0	23	theme	receptor	73:80	arg1	Identification					0:13	Identification	0:13	Identification	0:13	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	0	23	theme	receptor	73:80	arg1	analysis					49:56	expression analysis	38:56	expression analysis	38:56	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	5	24	theme	cysteine	909:916	arg1	Cys-193					940:946	Cys-193	940:946	Cys-193	940:946	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	5	24	theme	cysteine	909:916	arg1	Cys-115					928:934	Cys-115	928:934	Cys-115	928:934	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	5	24	theme	cysteine	909:916	arg1	residues					918:925	two cysteine residues	905:925	two cysteine residues (Cys-115 and Cys-193)	905:947	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	4	25	theme	highest	740:746	arg1	homology					748:755	the highest homology	736:755	the highest homology of its amino acid sequence	736:782	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	4	26	theme	5-HT	793:796	arg1	receptor					798:805	the 5-HT receptor	789:805	the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor	789:872	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	7	27	theme	alpha	1191:1195	arg1	helices					1197:1203	multiple alpha helices	1182:1203	multiple alpha helices which is separated by a helix-loop-helix (HLH) structure	1182:1260	The three-dimensional structure of the 5-HTHdh showed multiple alpha helices which is separated by a helix-loop-helix (HLH) structure.
31696430	0	28	theme	expression	38:47	arg1	analysis					49:56	expression analysis	38:56	expression analysis	38:56	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	2	29	theme	molecular	442:450	arg1	mass					452:455	a predicted molecular mass	430:455	a predicted molecular mass of 46.54 kDa	430:468	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	4	30	theme	acid	770:773	arg1	sequence					775:782	its amino acid sequence	760:782	its amino acid sequence	760:782	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	2	31	theme	acids	419:423	arg1	protein					398:404	a protein	396:404	a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94	396:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	31	theme	acids	419:423	arg1	sequence					353:360	The full-length nucleotide sequence	326:360	The full-length nucleotide sequence of Haliotis discus hannai	326:386	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	1	32	theme	various	275:281	arg1	aspects					283:289	various aspects	275:289	various aspects of reproduction and gametogenesis	275:323	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	6	33	theme	receptor	1039:1046	arg1	genes					1048:1052	other known 5-HT receptor genes	1022:1052	other known 5-HT receptor genes	1022:1052	Phylogenetic comparison with other known 5-HT receptor genes revealed that the 5-HTHdh is most closely related to the 5-HTHa receptor.
31696430	12	34	theme	H.	1893:1894	arg1	hannai					1903:1908	H. discus hannai	1893:1908	H. discus hannai	1893:1908	Our results suggest that 5-HTHdh synthesized in the neural ganglia may be involved in oocyte maturation and spawning of H. discus hannai.
31696430	6	35	theme	known	1028:1032	arg1	genes					1048:1052	other known 5-HT receptor genes	1022:1052	other known 5-HT receptor genes	1022:1052	Phylogenetic comparison with other known 5-HT receptor genes revealed that the 5-HTHdh is most closely related to the 5-HTHa receptor.
31696430	10	36	theme	pleuropedal	1539:1549	arg1	ganglion					1551:1558	pleuropedal ganglion	1539:1558	pleuropedal ganglion	1539:1558	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	3	37	theme	N-linked	650:657	arg1	sites					673:677	putative N-linked glycosylation sites	641:677	putative N-linked glycosylation sites	641:677	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	4	38	theme	lesser	837:842	arg1	extent					844:849	lesser extent	837:849	lesser extent of human 5-HT receptor	837:872	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	2	39	theme	nucleotide	342:351	arg1	protein					398:404	a protein	396:404	a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94	396:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	39	theme	nucleotide	342:351	arg1	sequence					353:360	The full-length nucleotide sequence	326:360	The full-length nucleotide sequence of Haliotis discus hannai	326:386	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	6	40	theme	5-HTHa	1111:1116	arg1	receptor					1118:1125	the 5-HTHa receptor	1107:1125	the 5-HTHa receptor	1107:1125	Phylogenetic comparison with other known 5-HT receptor genes revealed that the 5-HTHdh is most closely related to the 5-HTHa receptor.
31696430	3	41	theme	phosphorylation	692:706	arg1	motifs					718:723	several phosphorylation consensus motifs	684:723	several phosphorylation consensus motifs	684:723	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	1	42	theme	biogenic	198:205	arg1	receptor					177:184	Serotonin receptor	167:184	Serotonin receptor (5-HT)	167:191	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	1	42	theme	biogenic	198:205	arg1	amine					207:211	a biogenic amine	196:211	a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis	196:323	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	5	43	theme	disulfide	977:985	arg1	bond					987:990	a disulfide bond	975:990	a disulfide bond	975:990	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	11	44	theme	In	1635:1636	arg1	hybridization					1643:1655	In situ hybridization	1635:1655	In situ hybridization	1635:1655	In situ hybridization showed that the 5-HTHdh expressing neurosecretory cells were distributed in the cortex of the pleuropedal ganglion.
31696430	3	45	theme	structural	505:514	arg1	profile					516:522	The structural profile	501:522	The structural profile of 5-HTHdh	501:533	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	12	46	theme	neural	1825:1830	arg1	ganglia					1832:1838	the neural ganglia	1821:1838	the neural ganglia	1821:1838	Our results suggest that 5-HTHdh synthesized in the neural ganglia may be involved in oocyte maturation and spawning of H. discus hannai.
31696430	1	47	theme	reproduction	294:305	arg1	aspects					283:289	various aspects	275:289	various aspects of reproduction and gametogenesis	275:323	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	2	48	with	protein	398:404	arg1	point					486:490	isoelectric point	474:490	isoelectric point of 8.94	474:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	48	with	protein	398:404	arg1	mass					452:455	a predicted molecular mass	430:455	a predicted molecular mass of 46.54 kDa	430:468	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	4	49	theme	receptor	865:872	arg1	extent					844:849	lesser extent	837:849	lesser extent of human 5-HT receptor	837:872	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	3	50	gly	glycosylation	659:671	arg2	sites					673:677	putative N-linked glycosylation sites	641:677	putative N-linked glycosylation sites	641:677	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	10	51	theme	higher	1582:1587	arg1	temperature					1612:1622	higher effective accumulative temperature	1582:1622	higher effective accumulative temperature (1000 °C)	1582:1632	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	51	theme	higher	1582:1587	arg1	1000 °C					1625:1631	1000 °C	1625:1631	1000 °C	1625:1631	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	9	52	theme	gene	1444:1447	arg1	activity					1420:1427	the transcriptional activity	1400:1427	the transcriptional activity of the 5-HTHdh gene	1400:1447	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	11	53	theme	neurosecretory	1692:1705	arg1	cells					1707:1711	the 5-HTHdh expressing neurosecretory cells	1669:1711	the 5-HTHdh expressing neurosecretory cells	1669:1711	In situ hybridization showed that the 5-HTHdh expressing neurosecretory cells were distributed in the cortex of the pleuropedal ganglion.
31696430	11	54	theme	5-HTHdh	1673:1679	arg1	cells					1707:1711	the 5-HTHdh expressing neurosecretory cells	1669:1711	the 5-HTHdh expressing neurosecretory cells	1669:1711	In situ hybridization showed that the 5-HTHdh expressing neurosecretory cells were distributed in the cortex of the pleuropedal ganglion.
31696430	4	55	theme	human	854:858	arg1	receptor					865:872	human 5-HT receptor	854:872	human 5-HT receptor	854:872	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	10	56	theme	accumulative	1599:1610	arg1	temperature					1612:1622	higher effective accumulative temperature	1582:1622	higher effective accumulative temperature (1000 °C)	1582:1632	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	56	theme	accumulative	1599:1610	arg1	1000 °C					1625:1631	1000 °C	1625:1631	1000 °C	1625:1631	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	2	57	theme	discus	374:379	arg1	hannai					381:386	Haliotis discus hannai	365:386	Haliotis discus hannai	365:386	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	0	58	theme	abalone	134:140	arg1	process					111:117	the reproductive process	94:117	the reproductive process of the Pacific abalone	94:140	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	9	59	theme	ripening	1483:1490	arg1	stage					1492:1496	the ripening stage	1479:1496	the ripening stage	1479:1496	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	8	60	theme	Quantitative	1263:1274	arg1	PCR					1276:1278	Quantitative PCR	1263:1278	Quantitative PCR	1263:1278	Quantitative PCR demonstrated that the receptor mRNA was predominantly expressed in the pleuropedal ganglion.
31696430	0	61	theme	Haliotis	143:150	arg1	receptor					73:80	a serotonin receptor	61:80	a serotonin receptor involved in the reproductive process of the Pacific abalone	61:140	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	0	61	theme	Haliotis	143:150	arg1	hannai					159:164	Haliotis discus hannai	143:164	Haliotis discus hannai	143:164	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	3	62	theme	receptors	579:587	arg1	sites					673:677	putative N-linked glycosylation sites	641:677	putative N-linked glycosylation sites	641:677	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	62	theme	receptors	579:587	arg1	domains					632:638	seven hydrophobic transmembrane domains	600:638	seven hydrophobic transmembrane domains	600:638	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	62	theme	receptors	579:587	arg1	motifs					718:723	several phosphorylation consensus motifs	684:723	several phosphorylation consensus motifs	684:723	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	3	62	theme	receptors	579:587	arg1	features					549:556	key features	545:556	key features	545:556	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	6	63	theme	other	1022:1026	arg1	genes					1048:1052	other known 5-HT receptor genes	1022:1052	other known 5-HT receptor genes	1022:1052	Phylogenetic comparison with other known 5-HT receptor genes revealed that the 5-HTHdh is most closely related to the 5-HTHa receptor.
31696430	10	64	located	detected	1527:1534	arg1	temperature					1612:1622	higher effective accumulative temperature	1582:1622	higher effective accumulative temperature (1000 °C)	1582:1632	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	64	located	detected	1527:1534	arg2	expression					1512:1521	An exclusive expression	1499:1521	An exclusive expression	1499:1521	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	64	located	detected	1527:1534	arg1	ovary					1573:1577	ovary	1573:1577	ovary	1573:1577	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	64	located	detected	1527:1534	arg1	1000 °C					1625:1631	1000 °C	1625:1631	1000 °C	1625:1631	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	64	located	detected	1527:1534	arg1	ganglion					1551:1558	pleuropedal ganglion	1539:1558	pleuropedal ganglion	1539:1558	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	10	64	located	detected	1527:1534	arg1	testis					1561:1566	testis	1561:1566	testis	1561:1566	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	0	65	theme	serotonin	63:71	arg1	receptor					73:80	a serotonin receptor	61:80	a serotonin receptor involved in the reproductive process of the Pacific abalone	61:140	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	0	65	theme	serotonin	63:71	arg1	hannai					159:164	Haliotis discus hannai	143:164	Haliotis discus hannai	143:164	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	3	66	theme	hydrophobic	606:616	arg1	domains					632:638	seven hydrophobic transmembrane domains	600:638	seven hydrophobic transmembrane domains	600:638	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	5	67	contain	possesses	895:903	arg2	Cys-193					940:946	Cys-193	940:946	Cys-193	940:946	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	5	67	contain	possesses	895:903	arg1	sequence					886:893	The cloned sequence	875:893	The cloned sequence	875:893	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	5	67	contain	possesses	895:903	arg2	Cys-115					928:934	Cys-115	928:934	Cys-115	928:934	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	5	67	contain	possesses	895:903	arg2	residues					918:925	two cysteine residues	905:925	two cysteine residues (Cys-115 and Cys-193)	905:947	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	11	68	theme	ganglion	1763:1770	arg1	cortex					1737:1742	the cortex	1733:1742	the cortex of the pleuropedal ganglion	1733:1770	In situ hybridization showed that the 5-HTHdh expressing neurosecretory cells were distributed in the cortex of the pleuropedal ganglion.
31696430	9	69	from	differences	1385:1395	arg1	activity					1420:1427	the transcriptional activity	1400:1427	the transcriptional activity of the 5-HTHdh gene	1400:1447	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	2	70	theme	isoelectric	474:484	arg1	point					486:490	isoelectric point	474:490	isoelectric point of 8.94	474:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	4	71	theme	sequence	775:782	arg1	homology					748:755	the highest homology	736:755	the highest homology of its amino acid sequence	736:782	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	7	72	theme	multiple	1182:1189	arg1	helices					1197:1203	multiple alpha helices	1182:1203	multiple alpha helices which is separated by a helix-loop-helix (HLH) structure	1182:1260	The three-dimensional structure of the 5-HTHdh showed multiple alpha helices which is separated by a helix-loop-helix (HLH) structure.
31696430	8	73	theme	pleuropedal	1351:1361	arg1	ganglion					1363:1370	the pleuropedal ganglion	1347:1370	the pleuropedal ganglion	1347:1370	Quantitative PCR demonstrated that the receptor mRNA was predominantly expressed in the pleuropedal ganglion.
31696430	7	74	theme	5-HTHdh	1167:1173	arg1	structure					1150:1158	The three-dimensional structure	1128:1158	The three-dimensional structure of the 5-HTHdh	1128:1173	The three-dimensional structure of the 5-HTHdh showed multiple alpha helices which is separated by a helix-loop-helix (HLH) structure.
31696430	7	75	dep	helix-loop-helix	1229:1244	arg1	HLH					1247:1249	HLH	1247:1249	HLH	1247:1249	The three-dimensional structure of the 5-HTHdh showed multiple alpha helices which is separated by a helix-loop-helix (HLH) structure.
31696430	2	76	theme	predicted	432:440	arg1	mass					452:455	a predicted molecular mass	430:455	a predicted molecular mass of 46.54 kDa	430:468	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	77	theme	hannai	381:386	arg1	protein					398:404	a protein	396:404	a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94	396:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	77	theme	hannai	381:386	arg1	sequence					353:360	The full-length nucleotide sequence	326:360	The full-length nucleotide sequence of Haliotis discus hannai	326:386	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	5	78	dep	residues	918:925	arg1	Cys-193					940:946	Cys-193	940:946	Cys-193	940:946	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	5	78	dep	residues	918:925	arg1	Cys-115					928:934	Cys-115	928:934	Cys-115	928:934	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	5	78	dep	residues	918:925	arg1	residues					918:925	two cysteine residues	905:925	two cysteine residues (Cys-115 and Cys-193)	905:947	The cloned sequence possesses two cysteine residues (Cys-115 and Cys-193), which are likely to form a disulfide bond.
31696430	3	79	theme	glycosylation	659:671	arg1	sites					673:677	putative N-linked glycosylation sites	641:677	putative N-linked glycosylation sites	641:677	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	4	80	theme	amino	764:768	arg1	sequence					775:782	its amino acid sequence	760:782	its amino acid sequence	760:782	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	2	81	theme	amino	413:417	arg1	acids					419:423	417 amino acids	409:423	417 amino acids	409:423	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	7	82	theme	three-dimensional	1132:1148	arg1	structure					1150:1158	The three-dimensional structure	1128:1158	The three-dimensional structure of the 5-HTHdh	1128:1173	The three-dimensional structure of the 5-HTHdh showed multiple alpha helices which is separated by a helix-loop-helix (HLH) structure.
31696430	12	83	theme	discus	1896:1901	arg1	hannai					1903:1908	H. discus hannai	1893:1908	H. discus hannai	1893:1908	Our results suggest that 5-HTHdh synthesized in the neural ganglia may be involved in oocyte maturation and spawning of H. discus hannai.
31696430	6	84	theme	5-HT	1034:1037	arg1	genes					1048:1052	other known 5-HT receptor genes	1022:1052	other known 5-HT receptor genes	1022:1052	Phylogenetic comparison with other known 5-HT receptor genes revealed that the 5-HTHdh is most closely related to the 5-HTHa receptor.
31696430	2	85	theme	46.54 kDa	460:468	arg1	point					486:490	isoelectric point	474:490	isoelectric point of 8.94	474:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	85	theme	46.54 kDa	460:468	arg1	mass					452:455	a predicted molecular mass	430:455	a predicted molecular mass of 46.54 kDa	430:468	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	3	86	theme	putative	641:648	arg1	sites					673:677	putative N-linked glycosylation sites	641:677	putative N-linked glycosylation sites	641:677	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	0	87	theme	reproductive	98:109	arg1	process					111:117	the reproductive process	94:117	the reproductive process of the Pacific abalone	94:140	Identification, characterization, and expression analysis of a serotonin receptor involved in the reproductive process of the Pacific abalone, Haliotis discus hannai.
31696430	9	88	theme	Significant	1373:1383	arg1	differences					1385:1395	Significant differences	1373:1395	Significant differences in the transcriptional activity of the 5-HTHdh gene	1373:1447	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	12	89	theme	oocyte	1859:1864	arg1	maturation					1866:1875	oocyte maturation	1859:1875	oocyte maturation	1859:1875	Our results suggest that 5-HTHdh synthesized in the neural ganglia may be involved in oocyte maturation and spawning of H. discus hannai.
31696430	3	90	theme	several	684:690	arg1	motifs					718:723	several phosphorylation consensus motifs	684:723	several phosphorylation consensus motifs	684:723	The structural profile of 5-HTHdh displayed key features of G protein-coupled receptors, including seven hydrophobic transmembrane domains, putative N-linked glycosylation sites, and several phosphorylation consensus motifs.
31696430	12	91	theme	hannai	1903:1908	arg1	maturation					1866:1875	oocyte maturation	1859:1875	oocyte maturation	1859:1875	Our results suggest that 5-HTHdh synthesized in the neural ganglia may be involved in oocyte maturation and spawning of H. discus hannai.
31696430	12	91	theme	hannai	1903:1908	arg1	spawning					1881:1888	spawning	1881:1888	spawning	1881:1888	Our results suggest that 5-HTHdh synthesized in the neural ganglia may be involved in oocyte maturation and spawning of H. discus hannai.
31696430	2	92	theme	full-length	330:340	arg1	protein					398:404	a protein	396:404	a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94	396:498	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	2	92	theme	full-length	330:340	arg1	sequence					353:360	The full-length nucleotide sequence	326:360	The full-length nucleotide sequence of Haliotis discus hannai	326:386	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31696430	1	93	theme	gametogenesis	311:323	arg1	aspects					283:289	various aspects	275:289	various aspects of reproduction and gametogenesis	275:323	Serotonin receptor (5-HT) is a biogenic amine acting as a neurotransmitter and neuromodulator that mediates various aspects of reproduction and gametogenesis.
31696430	9	94	theme	transcriptional	1404:1418	arg1	activity					1420:1427	the transcriptional activity	1400:1427	the transcriptional activity of the 5-HTHdh gene	1400:1447	Significant differences in the transcriptional activity of the 5-HTHdh gene were observed in the ovary at the ripening stage.
31696430	10	95	theme	exclusive	1502:1510	arg1	expression					1512:1521	An exclusive expression	1499:1521	An exclusive expression	1499:1521	An exclusive expression was detected in pleuropedal ganglion, testis, and ovary at higher effective accumulative temperature (1000 °C).
31696430	4	96	theme	Haliotis	812:819	arg1	asinina					821:827	Haliotis asinina	812:827	Haliotis asinina	812:827	It shares the highest homology of its amino acid sequence with the 5-HT receptor from Haliotis asinina, and to lesser extent of human 5-HT receptor.
31696430	2	97	theme	Haliotis	365:372	arg1	hannai					381:386	Haliotis discus hannai	365:386	Haliotis discus hannai	365:386	The full-length nucleotide sequence of Haliotis discus hannai encodes a protein of 417 amino acids with a predicted molecular mass of 46.54 kDa and isoelectric point of 8.94.
31285765	9	0	theme	qPCR	954:957	arg1	assays					968:973	luciferase, qPCR and ChIP assays	942:973	assays	968:973	The mechanism of TWIST1 regulating PCOLCE transcription was elucidated by luciferase, qPCR and ChIP assays.
31285765	10	1	theme	high	1109:1112	arg1	expression					1121:1130	high PCOLCE expression	1109:1130	high PCOLCE expression in tissues	1109:1141	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	10	2	theme	PCOLCE	1206:1211	arg1	knockdown					1193:1201	the knockdown	1189:1201	the knockdown of PCOLCE by shRNAs	1189:1221	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	13	3	with	patients	1979:1986	arg1	osteosarcoma					2004:2015	metastatic osteosarcoma	1993:2015	metastatic osteosarcoma	1993:2015	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	9	4	theme	transcription	910:922	arg1	mechanism					872:880	The mechanism	868:880	The mechanism of TWIST1 regulating PCOLCE transcription	868:922	The mechanism of TWIST1 regulating PCOLCE transcription was elucidated by luciferase, qPCR and ChIP assays.
31285765	6	5	dep	in	555:556	arg1	vitro					558:562	vitro	558:562	vitro	558:562	The in vitro migration and invasion abilities of osteosarcoma cells were determined by a Transwell assay.
31285765	12	6	from	factor	1538:1543	arg1	metastasis					1548:1557	metastasis	1548:1557	metastasis	1548:1557	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	4	7	theme	direct	399:404	arg1	research					406:413	direct research	399:413	direct research on PCOLCE	399:423	However, direct research on PCOLCE has not been reported.
31285765	13	8	theme	osteosarcoma	1874:1885	arg1	metastasis					1860:1869	the lung metastasis	1851:1869	the lung metastasis of osteosarcoma	1851:1885	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	12	9	theme	transcription	1524:1536	arg1	factor					1538:1543	a key transcription factor	1518:1543	a key transcription factor in metastasis	1518:1557	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	9	theme	transcription	1524:1536	arg1	TWIST1					1510:1515	TWIST1	1510:1515	TWIST1	1510:1515	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	9	10	theme	ChIP	963:966	arg1	assays					968:973	luciferase, qPCR and ChIP assays	942:973	assays	968:973	The mechanism of TWIST1 regulating PCOLCE transcription was elucidated by luciferase, qPCR and ChIP assays.
31285765	10	11	theme	human	1021:1025	arg1	tissues					1040:1046	human osteosarcoma tissues	1021:1046	human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues	1021:1106	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	6	12	theme	cells	613:617	arg1	abilities					587:595	The in vitro migration and invasion abilities	551:595	The in vitro migration and invasion abilities of osteosarcoma cells	551:617	The in vitro migration and invasion abilities of osteosarcoma cells were determined by a Transwell assay.
31285765	8	13	theme	F	824:824	arg1	treatment					826:834	PNGase F treatment	817:834	PNGase F treatment combined with Western blotting	817:865	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	8	14	link	N-linked	764:771	arg1	acids					792:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	13	15	theme	metastatic	1993:2002	arg1	osteosarcoma					2004:2015	metastatic osteosarcoma	1993:2015	metastatic osteosarcoma	1993:2015	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	13	16	theme	new	1945:1947	arg1	strategy					1961:1968	a new therapeutic strategy	1943:1968	a new therapeutic strategy to treat patients with metastatic osteosarcoma	1943:2015	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	4	17	from	research	406:413	arg1	PCOLCE					418:423	PCOLCE	418:423	PCOLCE	418:423	However, direct research on PCOLCE has not been reported.
31285765	7	18	theme	osteosarcoma	727:738	arg1	metastasis					740:749	osteosarcoma metastasis	727:749	osteosarcoma metastasis	727:749	A spontaneous metastatic osteosarcoma model was established to assess osteosarcoma metastasis in vivo.
31285765	10	19	theme	osteosarcoma	1279:1290	arg1	cells					1292:1296	osteosarcoma cells	1279:1296	osteosarcoma cells	1279:1296	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	1	20	theme	Procollagen	71:81	arg1	enhancer					96:103	Procollagen C-proteinase enhancer	71:103	Procollagen C-proteinase enhancer protein (PCOLCE)	71:120	Procollagen C-proteinase enhancer protein (PCOLCE) was originally identified as an enhancer to facilitate the catalysis of procollagens by BMP1.
31285765	5	21	theme	RNA-seq	491:497	arg1	analysis					499:506	RNA-seq analysis	491:506	RNA-seq analysis from 4 normal and 16 osteosarcoma tissues	491:548	Methods: ECM candidates were identified by RNA-seq analysis from 4 normal and 16 osteosarcoma tissues.
31285765	8	22	theme	PNGase	817:822	arg1	treatment					826:834	PNGase F treatment	817:834	PNGase F treatment combined with Western blotting	817:865	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	11	23	from	functions	1483:1491	arg1	osteosarcoma					1496:1507	osteosarcoma	1496:1507	osteosarcoma	1496:1507	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	2	24	theme	corneal	279:285	arg1	repair					287:292	corneal repair	279:292	corneal repair	279:292	PCOLCE participates in the reconstitution of extracellular and corneal repair.
31285765	13	25	theme	lung	1855:1858	arg1	metastasis					1860:1869	the lung metastasis	1851:1869	the lung metastasis of osteosarcoma	1851:1885	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	6	26	theme	osteosarcoma	600:611	arg1	cells					613:617	osteosarcoma cells	600:617	osteosarcoma cells	600:617	The in vitro migration and invasion abilities of osteosarcoma cells were determined by a Transwell assay.
31285765	11	27	theme	wild-type	1321:1329	arg1	PCOLCE					1331:1336	wild-type PCOLCE	1321:1336	wild-type PCOLCE	1321:1336	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	1	28	theme	enhancer	96:103	arg1	protein					105:111	Procollagen C-proteinase enhancer protein	71:111	Procollagen C-proteinase enhancer protein (PCOLCE)	71:120	Procollagen C-proteinase enhancer protein (PCOLCE) was originally identified as an enhancer to facilitate the catalysis of procollagens by BMP1.
31285765	1	28	theme	enhancer	96:103	arg1	enhancer					154:161	an enhancer to facilitate the catalysis of procollagens by BMP1	151:213	an enhancer to facilitate the catalysis of procollagens by BMP1	151:213	Procollagen C-proteinase enhancer protein (PCOLCE) was originally identified as an enhancer to facilitate the catalysis of procollagens by BMP1.
31285765	1	28	theme	enhancer	96:103	arg1	PCOLCE					114:119	PCOLCE	114:119	PCOLCE	114:119	Procollagen C-proteinase enhancer protein (PCOLCE) was originally identified as an enhancer to facilitate the catalysis of procollagens by BMP1.
31285765	11	29	theme	PCOLCE	1446:1451	arg1	necessary					1465:1473	necessary	1465:1473	necessary	1465:1473	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	11	29	theme	PCOLCE	1446:1451	arg1	glycosylation					1429:1441	the glycosylation	1425:1441	the glycosylation of PCOLCE at Asn29	1425:1460	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	10	30	theme	patient	1166:1172	arg1	prognosis					1174:1182	a poor patient prognosis	1159:1182	a poor patient prognosis	1159:1182	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	11	31	theme	PCOLCE	1331:1336	arg1	overexpression					1303:1316	The overexpression	1299:1316	The overexpression of wild-type PCOLCE	1299:1336	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	10	32	theme	adjacent	1091:1098	arg1	tissues					1100:1106	noncancerous adjacent tissues	1078:1106	noncancerous adjacent tissues	1078:1106	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	5	33	theme	ECM	457:459	arg1	candidates					461:470	ECM candidates	457:470	ECM candidates	457:470	Methods: ECM candidates were identified by RNA-seq analysis from 4 normal and 16 osteosarcoma tissues.
31285765	5	34	from	normal	515:520	arg1	analysis					499:506	RNA-seq analysis	491:506	RNA-seq analysis from 4 normal and 16 osteosarcoma tissues	491:548	Methods: ECM candidates were identified by RNA-seq analysis from 4 normal and 16 osteosarcoma tissues.
31285765	10	35	theme	poor	1161:1164	arg1	prognosis					1174:1182	a poor patient prognosis	1159:1182	a poor patient prognosis	1159:1182	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	13	36	theme	therapeutic	1949:1959	arg1	strategy					1961:1968	a new therapeutic strategy	1943:1968	a new therapeutic strategy to treat patients with metastatic osteosarcoma	1943:2015	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	11	37	gly	glycosylation	1429:1441	arg1	Asn29					1456:1460	Asn29	1456:1460	Asn29	1456:1460	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	11	37	gly	glycosylation	1429:1441	arg2	Asn29					1456:1460	Asn29	1456:1460	Asn29	1456:1460	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	11	37	gly	glycosylation	1429:1441	arg1	PCOLCE					1446:1451	PCOLCE	1446:1451	PCOLCE	1446:1451	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	1	38	theme	procollagens	194:205	arg1	catalysis					181:189	the catalysis	177:189	the catalysis of procollagens	177:205	Procollagen C-proteinase enhancer protein (PCOLCE) was originally identified as an enhancer to facilitate the catalysis of procollagens by BMP1.
31285765	6	39	theme	invasion	578:585	arg1	abilities					587:595	The in vitro migration and invasion abilities	551:595	The in vitro migration and invasion abilities of osteosarcoma cells	551:617	The in vitro migration and invasion abilities of osteosarcoma cells were determined by a Transwell assay.
31285765	2	40	theme	repair	287:292	arg1	reconstitution					243:256	the reconstitution	239:256	the reconstitution of extracellular and corneal repair	239:292	PCOLCE participates in the reconstitution of extracellular and corneal repair.
31285765	12	41	theme	potential	1659:1667	arg1	COL5A1					1717:1722	COL5A1	1717:1722	COL5A1	1717:1722	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	41	theme	potential	1659:1667	arg1	COL8A2					1725:1730	COL8A2	1725:1730	COL8A2	1725:1730	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	41	theme	potential	1659:1667	arg1	COL1A1					1701:1706	COL1A1	1701:1706	COL1A1	1701:1706	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	41	theme	potential	1659:1667	arg1	COL1A2					1709:1714	COL1A2	1709:1714	COL1A2	1709:1714	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	41	theme	potential	1659:1667	arg1	COL10A1					1736:1742	COL10A1	1736:1742	COL10A1	1736:1742	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	41	theme	potential	1659:1667	arg1	substrates					1681:1690	its potential procollagen substrates	1655:1690	its potential procollagen substrates	1655:1690	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	42	theme	procollagen	1669:1679	arg1	COL5A1					1717:1722	COL5A1	1717:1722	COL5A1	1717:1722	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	42	theme	procollagen	1669:1679	arg1	COL8A2					1725:1730	COL8A2	1725:1730	COL8A2	1725:1730	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	42	theme	procollagen	1669:1679	arg1	COL1A1					1701:1706	COL1A1	1701:1706	COL1A1	1701:1706	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	42	theme	procollagen	1669:1679	arg1	COL1A2					1709:1714	COL1A2	1709:1714	COL1A2	1709:1714	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	42	theme	procollagen	1669:1679	arg1	COL10A1					1736:1742	COL10A1	1736:1742	COL10A1	1736:1742	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	42	theme	procollagen	1669:1679	arg1	substrates					1681:1690	its potential procollagen substrates	1655:1690	its potential procollagen substrates	1655:1690	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	9	43	theme	regulating	892:901	arg1	transcription					910:922	TWIST1 regulating PCOLCE transcription	885:922	TWIST1 regulating PCOLCE transcription	885:922	The mechanism of TWIST1 regulating PCOLCE transcription was elucidated by luciferase, qPCR and ChIP assays.
31285765	8	44	gly	glycosylated	773:784	arg1	acids					792:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	6	45	theme	migration	564:572	arg1	abilities					587:595	The in vitro migration and invasion abilities	551:595	The in vitro migration and invasion abilities of osteosarcoma cells	551:617	The in vitro migration and invasion abilities of osteosarcoma cells were determined by a Transwell assay.
31285765	12	46	theme	osteosarcoma	1586:1597	arg1	tissues					1599:1605	osteosarcoma tissues	1586:1605	osteosarcoma tissues	1586:1605	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	9	47	theme	PCOLCE	903:908	arg1	transcription					910:922	TWIST1 regulating PCOLCE transcription	885:922	TWIST1 regulating PCOLCE transcription	885:922	The mechanism of TWIST1 regulating PCOLCE transcription was elucidated by luciferase, qPCR and ChIP assays.
31285765	10	48	dep	migration	1236:1244	arg1	the					1232:1234	the	1232:1234	the	1232:1234	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	5	49	theme	osteosarcoma	529:540	arg1	tissues					542:548	16 osteosarcoma tissues	526:548	16 osteosarcoma tissues	526:548	Methods: ECM candidates were identified by RNA-seq analysis from 4 normal and 16 osteosarcoma tissues.
31285765	5	50	from	tissues	542:548	arg1	analysis					499:506	RNA-seq analysis	491:506	RNA-seq analysis from 4 normal and 16 osteosarcoma tissues	491:548	Methods: ECM candidates were identified by RNA-seq analysis from 4 normal and 16 osteosarcoma tissues.
31285765	3	51	theme	PCOLCE	312:317	arg1	elevation					299:307	The elevation	295:307	The elevation of PCOLCE in blood	295:326	The elevation of PCOLCE in blood indicates that breast cancer has metastasized into the bones.
31285765	8	52	theme	Western	850:856	arg1	blotting					858:865	Western blotting	850:865	Western blotting	850:865	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	6	53	theme	in	555:556	arg1	migration					564:572	in vitro migration	555:572	in vitro migration	555:572	The in vitro migration and invasion abilities of osteosarcoma cells were determined by a Transwell assay.
31285765	8	54	theme	N-linked	764:771	arg1	acids					792:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	7	55	theme	metastatic	671:680	arg1	model					695:699	A spontaneous metastatic osteosarcoma model	657:699	A spontaneous metastatic osteosarcoma model	657:699	A spontaneous metastatic osteosarcoma model was established to assess osteosarcoma metastasis in vivo.
31285765	10	56	theme	noncancerous	1078:1089	arg1	tissues					1100:1106	noncancerous adjacent tissues	1078:1106	noncancerous adjacent tissues	1078:1106	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	11	57	theme	N29Q	1351:1354	arg1	mutant					1356:1361	its N29Q mutant	1347:1361	its N29Q mutant	1347:1361	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	12	58	theme	key	1520:1522	arg1	factor					1538:1543	a key transcription factor	1518:1543	a key transcription factor in metastasis	1518:1557	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	12	58	theme	key	1520:1522	arg1	TWIST1					1510:1515	TWIST1	1510:1515	TWIST1	1510:1515	TWIST1, a key transcription factor in metastasis, was also overexpressed in osteosarcoma tissues and positively correlated with either PCOLCE or its potential procollagen substrates, such as COL1A1, COL1A2, COL5A1, COL8A2 and COL10A1.
31285765	10	59	theme	lung	1260:1263	arg1	metastasis					1265:1274	lung metastasis	1260:1274	lung metastasis	1260:1274	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	11	60	from	Asn29	1456:1460	arg1	necessary					1465:1473	necessary	1465:1473	necessary	1465:1473	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	11	60	from	Asn29	1456:1460	arg1	glycosylation					1429:1441	the glycosylation	1425:1441	the glycosylation of PCOLCE at Asn29	1425:1460	The overexpression of wild-type PCOLCE, but not its N29Q mutant, promoted migration, invasion and metastasis, indicating that the glycosylation of PCOLCE at Asn29 is necessary for its functions in osteosarcoma.
31285765	7	61	theme	osteosarcoma	682:693	arg1	model					695:699	A spontaneous metastatic osteosarcoma model	657:699	A spontaneous metastatic osteosarcoma model	657:699	A spontaneous metastatic osteosarcoma model was established to assess osteosarcoma metastasis in vivo.
31285765	10	62	theme	osteosarcoma	1027:1038	arg1	tissues					1040:1046	human osteosarcoma tissues	1021:1046	human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues	1021:1106	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	3	63	from	elevation	299:307	arg1	blood					322:326	blood	322:326	blood	322:326	The elevation of PCOLCE in blood indicates that breast cancer has metastasized into the bones.
31285765	1	64	theme	C-proteinase	83:94	arg1	enhancer					96:103	Procollagen C-proteinase enhancer	71:103	Procollagen C-proteinase enhancer protein (PCOLCE)	71:120	Procollagen C-proteinase enhancer protein (PCOLCE) was originally identified as an enhancer to facilitate the catalysis of procollagens by BMP1.
31285765	10	65	from	expression	1121:1130	arg1	tissues					1135:1141	tissues	1135:1141	tissues	1135:1141	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	2	66	theme	extracellular	261:273	arg1	reconstitution					243:256	the reconstitution	239:256	the reconstitution of extracellular and corneal repair	239:292	PCOLCE participates in the reconstitution of extracellular and corneal repair.
31285765	13	67	theme	critical	1824:1831	arg1	role					1833:1836	a critical role	1822:1836	a critical role	1822:1836	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	6	68	theme	Transwell	640:648	arg1	assay					650:654	a Transwell assay	638:654	a Transwell assay	638:654	The in vitro migration and invasion abilities of osteosarcoma cells were determined by a Transwell assay.
31285765	8	69	theme	glycosylated	773:784	arg1	acids					792:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	9	70	theme	luciferase	942:951	arg1	assays					968:973	luciferase, qPCR and ChIP assays	942:973	assays	968:973	The mechanism of TWIST1 regulating PCOLCE transcription was elucidated by luciferase, qPCR and ChIP assays.
31285765	7	71	theme	spontaneous	659:669	arg1	model					695:699	A spontaneous metastatic osteosarcoma model	657:699	A spontaneous metastatic osteosarcoma model	657:699	A spontaneous metastatic osteosarcoma model was established to assess osteosarcoma metastasis in vivo.
31285765	9	72	theme	TWIST1	885:890	arg1	transcription					910:922	TWIST1 regulating PCOLCE transcription	885:922	TWIST1 regulating PCOLCE transcription	885:922	The mechanism of TWIST1 regulating PCOLCE transcription was elucidated by luciferase, qPCR and ChIP assays.
31285765	13	73	theme	PCOLCE	1914:1919	arg1	up-regulation					1897:1909	this up-regulation	1892:1909	this up-regulation of PCOLCE by TWIST1	1892:1929	Conclusion: Our findings are the first to provide evidence that PCOLCE plays a critical role in promoting the lung metastasis of osteosarcoma, and this up-regulation of PCOLCE by TWIST1 may lead to a new therapeutic strategy to treat patients with metastatic osteosarcoma.
31285765	3	74	theme	breast	343:348	arg1	cancer					350:355	breast cancer	343:355	breast cancer	343:355	The elevation of PCOLCE in blood indicates that breast cancer has metastasized into the bones.
31285765	10	75	theme	PCOLCE	1114:1119	arg1	expression					1121:1130	high PCOLCE expression	1109:1130	high PCOLCE expression in tissues	1109:1141	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	0	76	theme	PCOLCE	17:22	arg1	Up-regulation					0:12	Up-regulation	0:12	Up-regulation of PCOLCE by TWIST1	0:32	Up-regulation of PCOLCE by TWIST1 promotes metastasis in Osteosarcoma.
31285765	8	77	theme	amino	786:790	arg1	acids					792:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids	760:796	The N-linked glycosylated amino acids were identified by PNGase F treatment combined with Western blotting.
31285765	10	78	theme	cells	1292:1296	arg1	invasion					1247:1254	invasion	1247:1254	invasion	1247:1254	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	10	78	theme	cells	1292:1296	arg1	metastasis					1265:1274	lung metastasis	1260:1274	lung metastasis	1260:1274	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	10	78	theme	cells	1292:1296	arg1	migration					1236:1244	migration	1236:1244	migration	1236:1244	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
31285765	10	79	from	expression	1064:1073	arg1	tissues					1100:1106	noncancerous adjacent tissues	1078:1106	noncancerous adjacent tissues	1078:1106	Results: PCOLCE was markedly up-regulated in human osteosarcoma tissues compared to its expression in noncancerous adjacent tissues; high PCOLCE expression in tissues correlated with a poor patient prognosis, and the knockdown of PCOLCE by shRNAs impaired the migration, invasion and lung metastasis of osteosarcoma cells.
30962950	1	0	gly	glycoproteins	165:177	arg1	glycoproteins					165:177	glycoproteins	165:177	glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC)	165:253	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	8	1	theme	in	1208:1209	arg1	apoptosis					1217:1225	in vitro apoptosis	1208:1225	in vitro apoptosis	1208:1225	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	4	2	theme	Serum	630:634	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	2	theme	Serum	630:634	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	2	theme	Serum	630:634	arg1	cf-QSOX1					684:691	cf-QSOX1	684:691	cf-QSOX1	684:691	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	10	3	theme	tumor	1581:1585	arg1	levels					1593:1598	serum cf-QSOX1-S and tumor QSOX1 levels	1560:1598	levels	1593:1598	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	1	4	from	role	290:293	arg1	metastasis					302:311	HCC metastasis	298:311	HCC metastasis	298:311	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	9	5	theme	demonstrable	1476:1487	arg1	effect					1489:1494	no demonstrable effect	1473:1494	no demonstrable effect on invasion or metastasis of HCC cells	1473:1533	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	3	6	theme	HCC	582:584	arg1	tissues					586:592	193 HCC tissues	578:592	193 HCC tissues using immunohistochemical staining	578:627	The prognostic significance of candidate glycoproteins was then validated in 193 HCC tissues using immunohistochemical staining.
30962950	8	7	theme	nude	1309:1312	arg1	models					1319:1324	nude mice models	1309:1324	nude mice models bearing human HCC	1309:1342	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	1	8	theme	hepatocellular	224:237	arg1	HCC					250:252	HCC	250:252	HCC	250:252	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	1	8	theme	hepatocellular	224:237	arg1	carcinoma					239:247	hepatocellular carcinoma	224:247	hepatocellular carcinoma (HCC)	224:253	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	8	9	theme	HCC	1267:1269	arg1	cells					1271:1275	HCC cells	1267:1275	HCC cells	1267:1275	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	10	10	gly	core-fucosylated	1663:1678	arg1	glycan					1680:1685	its core-fucosylated glycan	1659:1685	its core-fucosylated glycan at Asn-130	1659:1696	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	6	11	theme	serum	955:959	arg1	cf-QSOX1					961:968	serum cf-QSOX1	955:968	serum cf-QSOX1	955:968	As was seen with serum cf-QSOX1, QSOX1 in HCC tissues was further shown to be significantly associated with good patient outcome.
30962950	9	12	theme	mutant	1378:1383	arg1	version					1385:1391	a mutant version	1376:1391	a mutant version of QSOX1-S	1376:1402	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	8	13	theme	human	1334:1338	arg1	HCC					1340:1342	human HCC	1334:1342	human HCC	1334:1342	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	4	14	gly	glycoprotein	733:744	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	14	gly	glycoprotein	733:744	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	2	15	with	patients	470:477	arg1	HCC					496:498	early-stage HCC	484:498	early-stage HCC	484:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	9	16	theme	cells	1529:1533	arg1	effect					1489:1494	no demonstrable effect	1473:1494	no demonstrable effect on invasion or metastasis of HCC cells	1473:1533	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	4	17	theme	leading	714:720	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	17	theme	leading	714:720	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	5	18	theme	high	811:814	arg1	levels					831:836	high serum cf-QSOX1 levels	811:836	high serum cf-QSOX1 levels	811:836	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	5	19	theme	serum	922:926	arg1	cf-QSOX1					928:935	low serum cf-QSOX1	918:935	low serum cf-QSOX1	918:935	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	2	20	gly	glycoproteins	422:434	arg1	glycoproteins					422:434	recurrence-related N-linked glycoproteins	394:434	recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC	394:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	5	21	theme	cf-QSOX1	822:829	arg1	levels					831:836	high serum cf-QSOX1 levels	811:836	high serum cf-QSOX1 levels	811:836	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	2	22	from	samples	451:457	arg1	glycoproteins					422:434	recurrence-related N-linked glycoproteins	394:434	recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC	394:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	8	23	dep	in	1208:1209	arg1	vitro					1211:1215	vitro	1211:1215	vitro	1211:1215	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	3	24	gly	glycoproteins	542:554	arg1	glycoproteins					542:554	candidate glycoproteins	532:554	candidate glycoproteins	532:554	The prognostic significance of candidate glycoproteins was then validated in 193 HCC tissues using immunohistochemical staining.
30962950	0	25	theme	hepatocellular	93:106	arg1	carcinoma					108:116	hepatocellular carcinoma	93:116	hepatocellular carcinoma	93:116	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	1	26	theme	present	135:141	arg1	study					143:147	the present study	131:147	the present study	131:147	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	0	27	from	effect	45:50	arg1	metastasis					79:88	metastasis	79:88	metastasis	79:88	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	0	27	from	effect	45:50	arg1	invasion					66:73	invasion	66:73	invasion	66:73	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	0	28	theme	Core	0:3	arg1	fucosylated					5:15	Core fucosylated	0:15	Core fucosylated	0:15	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	1	29	theme	potential	280:288	arg1	role					290:293	their potential role	274:293	their potential role in HCC metastasis	274:311	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	2	30	theme	serum	445:449	arg1	samples					451:457	100 serum samples	441:457	100 serum samples taken from patients with early-stage HCC	441:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	1	31	theme	study	143:147	arg1	goal					123:126	The goal	119:126	The goal of the present study	119:147	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	2	32	theme	early-stage	484:494	arg1	HCC					496:498	early-stage HCC	484:498	early-stage HCC	484:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	2	33	theme	N-linked	413:420	arg1	glycoproteins					422:434	recurrence-related N-linked glycoproteins	394:434	recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC	394:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	9	34	theme	version	1385:1391	arg1	overexpression					1358:1371	overexpression	1358:1371	overexpression	1358:1371	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	7	35	dep	Gain-functional	1068:1082	arg1	analyses					1104:1111	analyses	1104:1111	analyses	1104:1111	Gain-functional and loss-functional analyses of QSOX1-S were performed in vitro and in vivo.
30962950	0	36	theme	QSOX1-S	55:61	arg1	effect					45:50	inhibitory effect	34:50	inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma	34:116	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	9	37	theme	QSOX1-S	1396:1402	arg1	version					1385:1391	a mutant version	1376:1391	a mutant version of QSOX1-S	1376:1402	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	9	38	from	effect	1489:1494	arg1	metastasis					1511:1520	metastasis	1511:1520	metastasis	1511:1520	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	9	38	from	effect	1489:1494	arg1	invasion					1499:1506	invasion	1499:1506	invasion	1499:1506	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	6	39	from	QSOX1	971:975	arg1	tissues					984:990	HCC tissues	980:990	HCC tissues	980:990	As was seen with serum cf-QSOX1, QSOX1 in HCC tissues was further shown to be significantly associated with good patient outcome.
30962950	1	40	theme	carcinoma	239:247	arg1	relapse					213:219	the postoperative relapse	195:219	the postoperative relapse of hepatocellular carcinoma (HCC)	195:253	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	10	41	from	Asn-130	1690:1696	arg1	glycan					1680:1685	its core-fucosylated glycan	1659:1685	its core-fucosylated glycan at Asn-130	1659:1696	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	4	42	theme	core	636:639	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	42	theme	core	636:639	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	42	theme	core	636:639	arg1	cf-QSOX1					684:691	cf-QSOX1	684:691	cf-QSOX1	684:691	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	6	43	theme	patient	1051:1057	arg1	outcome					1059:1065	good patient outcome	1046:1065	good patient outcome	1046:1065	As was seen with serum cf-QSOX1, QSOX1 in HCC tissues was further shown to be significantly associated with good patient outcome.
30962950	3	44	theme	candidate	532:540	arg1	glycoproteins					542:554	candidate glycoproteins	532:554	candidate glycoproteins	532:554	The prognostic significance of candidate glycoproteins was then validated in 193 HCC tissues using immunohistochemical staining.
30962950	4	45	theme	quiescin	653:660	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	45	theme	quiescin	653:660	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	45	theme	quiescin	653:660	arg1	cf-QSOX1					684:691	cf-QSOX1	684:691	cf-QSOX1	684:691	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	10	46	theme	serum	1560:1564	arg1	cf-QSOX1-S					1566:1575	serum cf-QSOX1-S and tumor QSOX1 levels	1560:1598	cf-QSOX1-S	1566:1575	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	10	47	theme	QSOX1-S	1740:1746	arg1	effects					1729:1735	the inhibitory effects	1714:1735	the inhibitory effects of QSOX1-S on invasion and metastasis of HCC	1714:1780	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	9	48	theme	core-fucosylated	1430:1445	arg1	glycan					1447:1452	the core-fucosylated glycan	1426:1452	the core-fucosylated glycan	1426:1452	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	10	49	from	recurrence	1627:1636	arg1	patients					1645:1652	HCC patients	1641:1652	HCC patients	1641:1652	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	10	50	theme	HCC	1778:1780	arg1	metastasis					1764:1773	metastasis	1764:1773	metastasis	1764:1773	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	10	50	theme	HCC	1778:1780	arg1	invasion					1751:1758	invasion	1751:1758	invasion	1751:1758	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	10	51	from	effects	1729:1735	arg1	metastasis					1764:1773	metastasis	1764:1773	metastasis	1764:1773	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	10	51	from	effects	1729:1735	arg1	invasion					1751:1758	invasion	1751:1758	invasion	1751:1758	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	10	52	theme	QSOX1	1587:1591	arg1	levels					1593:1598	serum cf-QSOX1-S and tumor QSOX1 levels	1560:1598	levels	1593:1598	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	8	53	theme	cells	1271:1275	arg1	capacity					1255:1262	the invasive capacity	1242:1262	the invasive capacity of HCC cells	1242:1275	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	7	54	theme	QSOX1-S	1116:1122	arg1	Gain-functional					1068:1082	Gain-functional	1068:1082	Gain-functional	1068:1082	Gain-functional and loss-functional analyses of QSOX1-S were performed in vitro and in vivo.
30962950	3	55	theme	193	578:580	arg1	tissues					586:592	193 HCC tissues	578:592	193 HCC tissues using immunohistochemical staining	578:627	The prognostic significance of candidate glycoproteins was then validated in 193 HCC tissues using immunohistochemical staining.
30962950	1	56	theme	postoperative	199:211	arg1	relapse					213:219	the postoperative relapse	195:219	the postoperative relapse of hepatocellular carcinoma (HCC)	195:253	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	6	57	theme	HCC	980:982	arg1	tissues					984:990	HCC tissues	980:990	HCC tissues	980:990	As was seen with serum cf-QSOX1, QSOX1 in HCC tissues was further shown to be significantly associated with good patient outcome.
30962950	8	58	theme	lung	1290:1293	arg1	metastasis					1295:1304	lung metastasis	1290:1304	lung metastasis	1290:1304	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	3	59	theme	prognostic	505:514	arg1	significance					516:527	The prognostic significance	501:527	The prognostic significance of candidate glycoproteins	501:554	The prognostic significance of candidate glycoproteins was then validated in 193 HCC tissues using immunohistochemical staining.
30962950	8	60	theme	invasive	1246:1253	arg1	capacity					1255:1262	the invasive capacity	1242:1262	the invasive capacity of HCC cells	1242:1275	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	5	61	with	Patients	797:804	arg1	levels					831:836	high serum cf-QSOX1 levels	811:836	high serum cf-QSOX1 levels	811:836	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	10	62	theme	HCC	1641:1643	arg1	patients					1645:1652	HCC patients	1641:1652	HCC patients	1641:1652	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	3	63	theme	immunohistochemical	600:618	arg1	staining					620:627	immunohistochemical staining	600:627	immunohistochemical staining	600:627	The prognostic significance of candidate glycoproteins was then validated in 193 HCC tissues using immunohistochemical staining.
30962950	8	64	theme	mice	1314:1317	arg1	models					1319:1324	nude mice models	1309:1324	nude mice models bearing human HCC	1309:1342	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	9	65	theme	HCC	1525:1527	arg1	cells					1529:1533	HCC cells	1525:1533	HCC cells	1525:1533	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	6	66	theme	good	1046:1049	arg1	outcome					1059:1065	good patient outcome	1046:1065	good patient outcome	1046:1065	As was seen with serum cf-QSOX1, QSOX1 in HCC tissues was further shown to be significantly associated with good patient outcome.
30962950	5	67	contain	had	838:840	arg2	time					865:868	a significantly longer time	842:868	a significantly longer time to recurrence (TTR)	842:888	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	5	67	contain	had	838:840	arg1	Patients					797:804	Patients	797:804	Patients with high serum cf-QSOX1 levels	797:836	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	5	68	theme	low	918:920	arg1	cf-QSOX1					928:935	low serum cf-QSOX1	918:935	low serum cf-QSOX1	918:935	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	5	69	theme	serum	816:820	arg1	levels					831:836	high serum cf-QSOX1 levels	811:836	high serum cf-QSOX1 levels	811:836	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	2	70	used	used	360:363	arg2	method					316:321	A method	314:321	A method for quantitating N-glycoproteome	314:354	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	4	71	theme	prognostic	722:731	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	71	theme	prognostic	722:731	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	0	72	theme	carcinoma	108:116	arg1	metastasis					79:88	metastasis	79:88	metastasis	79:88	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	0	72	theme	carcinoma	108:116	arg1	invasion					66:73	invasion	66:73	invasion	66:73	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	4	73	gly	fucosylated	641:651	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	73	gly	fucosylated	641:651	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	73	gly	fucosylated	641:651	arg1	cf-QSOX1					684:691	cf-QSOX1	684:691	cf-QSOX1	684:691	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	10	74	theme	core-fucosylated	1663:1678	arg1	glycan					1680:1685	its core-fucosylated glycan	1659:1685	its core-fucosylated glycan at Asn-130	1659:1696	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	5	75	theme	longer	858:863	arg1	time					865:868	a significantly longer time	842:868	a significantly longer time to recurrence (TTR)	842:888	Patients with high serum cf-QSOX1 levels had a significantly longer time to recurrence (TTR) as compared with those with low serum cf-QSOX1.
30962950	4	76	theme	HCC	781:783	arg1	recurrence					785:794	HCC recurrence	781:794	HCC recurrence	781:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	0	77	theme	inhibitory	34:43	arg1	effect					45:50	inhibitory effect	34:50	inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma	34:116	Core fucosylated glycan-dependent inhibitory effect of QSOX1-S on invasion and metastasis of hepatocellular carcinoma.
30962950	1	78	theme	HCC	298:300	arg1	metastasis					302:311	HCC metastasis	298:311	HCC metastasis	298:311	The goal of the present study was to identify glycoproteins associated with the postoperative relapse of hepatocellular carcinoma (HCC) and to investigate their potential role in HCC metastasis.
30962950	2	79	theme	recurrence-related	394:411	arg1	glycoproteins					422:434	recurrence-related N-linked glycoproteins	394:434	recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC	394:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	2	80	link	N-linked	413:420	arg1	glycoproteins					422:434	recurrence-related N-linked glycoproteins	394:434	recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC	394:498	A method for quantitating N-glycoproteome was used to screen for, and identify, recurrence-related N-linked glycoproteins from 100 serum samples taken from patients with early-stage HCC.
30962950	10	81	theme	inhibitory	1718:1727	arg1	effects					1729:1735	the inhibitory effects	1714:1735	the inhibitory effects of QSOX1-S on invasion and metastasis of HCC	1714:1780	Our study suggests that serum cf-QSOX1-S and tumor QSOX1 levels are helpful for predicting recurrence in HCC patients, and its core-fucosylated glycan at Asn-130 is critical for the inhibitory effects of QSOX1-S on invasion and metastasis of HCC.
30962950	4	82	theme	fucosylated	641:651	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	82	theme	fucosylated	641:651	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	82	theme	fucosylated	641:651	arg1	cf-QSOX1					684:691	cf-QSOX1	684:691	cf-QSOX1	684:691	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	9	83	gly	core-fucosylated	1430:1445	arg1	glycan					1447:1452	the core-fucosylated glycan	1426:1452	the core-fucosylated glycan	1426:1452	Furthermore, overexpression of a mutant version of QSOX1-S, which had eliminated the core-fucosylated glycan at Asn-130, showed no demonstrable effect on invasion or metastasis of HCC cells.
30962950	8	84	theme	QSOX1-S	1161:1167	arg1	overexpression					1169:1182	QSOX1-S overexpression	1161:1182	QSOX1-S overexpression	1161:1182	QSOX1-S overexpression significantly increased in vitro apoptosis, but decreased the invasive capacity of HCC cells, and reduced lung metastasis in nude mice models bearing human HCC.
30962950	4	85	theme	sulfhydryl	662:671	arg1	oxidase					673:679	Serum core fucosylated quiescin sulfhydryl oxidase 1	630:681	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1)	630:692	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	85	theme	sulfhydryl	662:671	arg1	glycoprotein					733:744	a leading prognostic glycoprotein	712:744	a leading prognostic glycoprotein that significantly correlated with HCC recurrence	712:794	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	4	85	theme	sulfhydryl	662:671	arg1	cf-QSOX1					684:691	cf-QSOX1	684:691	cf-QSOX1	684:691	Serum core fucosylated quiescin sulfhydryl oxidase 1 (cf-QSOX1) was identified as a leading prognostic glycoprotein that significantly correlated with HCC recurrence.
30962950	3	86	theme	glycoproteins	542:554	arg1	significance					516:527	The prognostic significance	501:527	The prognostic significance of candidate glycoproteins	501:554	The prognostic significance of candidate glycoproteins was then validated in 193 HCC tissues using immunohistochemical staining.
30487799	9	0	theme	ionization	1434:1443	arg1	analysis					1445:1452	Matrix-assisted laser desorption ionization analysis	1401:1452	Matrix-assisted laser desorption ionization analysis of released glycans	1401:1472	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30487799	8	1	located	found	1369:1373	arg1	glycosite					1390:1398	the Asn-565 glycosite	1378:1398	the Asn-565 glycosite	1378:1398	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	8	1	located	found	1369:1373	arg2	traces					1313:1318	only traces	1308:1318	only traces of complex-type and no high-mannose glycans	1308:1362	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	6	2	with	analysis	914:921	arg1	spectrometry					986:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	10	3	theme	unique	1611:1616	arg1	features					1627:1634	unique N-glycan features	1611:1634	unique N-glycan features	1611:1634	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	2	4	theme	higher	258:263	arg1	vertebrates					265:275	higher vertebrates	258:275	higher vertebrates	258:275	The N-linked carbohydrates presenting on IgM have been well documented in higher vertebrates, but little is known regarding site-specific N-glycan characteristics in teleost IgM.
30487799	1	5	theme	major	95:99	arg1	M					80:80	Immunoglobulin M	65:80	Immunoglobulin M (IgM)	65:86	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	1	5	theme	major	95:99	arg1	antibody					101:108	the major antibody	91:108	the major antibody	91:108	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	6	6	theme	serum	1194:1198	arg1	IgM					1200:1202	serum IgM	1194:1202	grass carp serum IgM	1183:1202	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	3	7	theme	serum	510:514	arg1	IgM					516:518	serum IgM	510:518	the grass carp serum IgM	495:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	5	8	theme	monomeric	819:827	arg1	IgM					829:831	monomeric IgM	819:831	monomeric IgM	819:831	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	6	9	theme	grass	1183:1187	arg1	carp					1189:1192	grass carp serum IgM	1183:1202	grass carp serum IgM	1183:1202	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	1	10	theme	humoral	157:163	arg1	immunity					174:181	humoral adaptive immunity	157:181	humoral adaptive immunity	157:181	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	9	11	theme	released	1457:1464	arg1	glycans					1466:1472	released glycans	1457:1472	released glycans	1457:1472	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30487799	5	12	from	decrease	711:718	arg1	level					727:731	the level	723:731	the level of occupancy at the Asn-565 glycosite	723:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	6	13	theme	Glycopeptide	901:912	arg1	analysis					914:921	Glycopeptide analysis	901:921	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry	901:997	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	9	14	theme	carbohydrates	1513:1525	arg1	majority					1501:1508	the overwhelming majority	1484:1508	the overwhelming majority of carbohydrates were of the complex-type	1484:1550	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30487799	2	15	theme	N-linked	188:195	arg1	carbohydrates					197:209	The N-linked carbohydrates	184:209	The N-linked carbohydrates presenting on IgM	184:227	The N-linked carbohydrates presenting on IgM have been well documented in higher vertebrates, but little is known regarding site-specific N-glycan characteristics in teleost IgM.
30487799	5	16	theme	Asn-565	861:867	arg1	occupancy					848:856	no glycan occupancy	838:856	no glycan occupancy of Asn-565	838:867	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	5	17	gly	occupancy	848:856	arg2	Asn-565					861:867	Asn-565	861:867	Asn-565	861:867	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	7	18	from	site	1234:1237	arg1	variation					1212:1220	Glycan variation	1205:1220	Glycan variation at a single site	1205:1237	Glycan variation at a single site was greatest at the Asn-262 glycosite.
30487799	8	19	theme	only	1308:1311	arg1	traces					1313:1318	only traces	1308:1318	only traces of complex-type and no high-mannose glycans	1308:1362	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	10	20	gly	glycosites	1697:1706	arg2	glycosites					1697:1706	individual glycosites	1686:1706	individual glycosites	1686:1706	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	1	21	theme	teleost	113:119	arg1	fish					121:124	teleost fish	113:124	teleost fish	113:124	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	5	22	theme	occupancy	736:744	arg1	level					727:731	the level	723:731	the level of occupancy at the Asn-565 glycosite	723:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	5	23	located	observed	873:880	arg1	IgM					896:898	tetrameric IgM	885:898	tetrameric IgM	885:898	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	5	23	located	observed	873:880	arg2	occupancy					848:856	no glycan occupancy	838:856	no glycan occupancy of Asn-565	838:867	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	4	24	used	occupied	690:697	arg2	Asn-565					637:643	Asn-565	637:643	Asn-565 at the C-terminal tailpiece	637:671	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	4	24	used	occupied	690:697	arg2	tailpiece					663:671	the C-terminal tailpiece	648:671	the C-terminal tailpiece	648:671	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	6	25	theme	tandem	974:979	arg1	spectrometry					986:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	8	26	theme	high-mannose	1343:1354	arg1	glycans					1356:1362	complex-type and no high-mannose glycans	1323:1362	glycans	1356:1362	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	5	27	theme	striking	702:709	arg1	decrease					711:718	A striking decrease	700:718	A striking decrease in the level of occupancy at the Asn-565 glycosite	700:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	1	28	theme	Immunoglobulin	65:78	arg1	M					80:80	Immunoglobulin M	65:80	Immunoglobulin M (IgM)	65:86	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	1	28	theme	Immunoglobulin	65:78	arg1	antibody					101:108	the major antibody	91:108	the major antibody	91:108	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	1	28	theme	Immunoglobulin	65:78	arg1	IgM					83:85	IgM	83:85	IgM	83:85	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	6	29	theme	chromatography-electrospray	935:961	arg1	spectrometry					986:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	3	30	dep	characterize	375:386	arg1	to					372:373	to	372:373	to	372:373	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	10	31	attach	attached	1674:1681	arg1	glycosites					1697:1706	individual glycosites	1686:1706	individual glycosites	1686:1706	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	10	31	attach	attached	1674:1681	arg2	oligosaccharides					1657:1672	highly processed oligosaccharides	1640:1672	highly processed oligosaccharides attached to individual glycosites	1640:1706	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	3	32	gly	glycosylation	473:485	arg2	carp					505:508	the grass carp serum IgM	495:518	the grass carp serum IgM	495:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	3	32	gly	glycosylation	473:485	arg1	carp					505:508	the grass carp serum IgM	495:518	the grass carp serum IgM	495:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	3	32	gly	glycosylation	473:485	arg2	site					487:490	each glycosylation site	468:490	each glycosylation site of the grass carp serum IgM	468:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	0	33	theme	Site-Specific	0:12	arg1	Characterization					23:38	Site-Specific N-Glycan Characterization	0:38	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.	0:63	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.
30487799	5	34	theme	tetrameric	885:894	arg1	IgM					896:898	tetrameric IgM	885:898	tetrameric IgM	885:898	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	8	35	theme	Asn-565	1382:1388	arg1	glycosite					1390:1398	the Asn-565 glycosite	1378:1398	the Asn-565 glycosite	1378:1398	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	5	36	theme	dimeric	787:793	arg1	IgM					795:797	dimeric IgM	787:797	dimeric IgM	787:797	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	6	37	theme	substantial	1041:1051	arg1	heterogeneity					1053:1065	substantial heterogeneity	1041:1065	substantial heterogeneity	1041:1065	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	3	38	theme	site-specific	394:406	arg1	N-glycans					408:416	these site-specific N-glycans	388:416	these site-specific N-glycans	388:416	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	3	39	theme	first	436:440	arg1	study					442:446	the first study	432:446	the first study of the N-glycans of each glycosylation site of the grass carp serum IgM	432:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	0	40	theme	Grass	43:47	arg1	IgM					60:62	Grass Carp Serum IgM	43:62	Grass Carp Serum IgM	43:62	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.
30487799	2	41	theme	N-glycan	322:329	arg1	characteristics					331:345	site-specific N-glycan characteristics	308:345	site-specific N-glycan characteristics	308:345	The N-linked carbohydrates presenting on IgM have been well documented in higher vertebrates, but little is known regarding site-specific N-glycan characteristics in teleost IgM.
30487799	0	42	theme	Serum	54:58	arg1	IgM					60:62	Grass Carp Serum IgM	43:62	Grass Carp Serum IgM	43:62	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.
30487799	3	43	theme	N-glycans	455:463	arg1	study					442:446	the first study	432:446	the first study of the N-glycans of each glycosylation site of the grass carp serum IgM	432:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	8	44	gly	glycosite	1390:1398	arg2	glycosite					1390:1398	the Asn-565 glycosite	1378:1398	the Asn-565 glycosite	1378:1398	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	10	45	theme	serum	1592:1596	arg1	IgM					1598:1600	grass carp serum IgM	1581:1600	grass carp serum IgM	1581:1600	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	5	46	gly	glycosite	761:769	arg2	glycosite					761:769	the Asn-565 glycosite	749:769	the Asn-565 glycosite	749:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	9	47	theme	glycans	1466:1472	arg1	analysis					1445:1452	Matrix-assisted laser desorption ionization analysis	1401:1452	Matrix-assisted laser desorption ionization analysis of released glycans	1401:1472	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30487799	9	48	theme	Matrix-assisted	1401:1415	arg1	ionization					1434:1443	Matrix-assisted laser desorption ionization	1401:1443	Matrix-assisted laser desorption ionization analysis of released glycans	1401:1472	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30487799	5	49	theme	Asn-565	753:759	arg1	glycosite					761:769	the Asn-565 glycosite	749:769	the Asn-565 glycosite	749:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	10	50	theme	grass	1581:1585	arg1	carp					1587:1590	grass carp	1581:1590	grass carp serum IgM	1581:1600	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	4	51	gly	glycosylated	617:628	arg1	residues					591:598	the Asn-262, Asn-303, and Asn-426 residues	557:598	the Asn-262, Asn-303, and Asn-426 residues	557:598	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	3	52	theme	site	487:490	arg1	N-glycans					455:463	the N-glycans	451:463	the N-glycans of each glycosylation site of the grass carp serum IgM	451:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	9	53	theme	desorption	1423:1432	arg1	ionization					1434:1443	Matrix-assisted laser desorption ionization	1401:1443	Matrix-assisted laser desorption ionization analysis of released glycans	1401:1472	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30487799	10	54	theme	N-glycan	1618:1625	arg1	features					1627:1634	unique N-glycan features	1611:1634	unique N-glycan features	1611:1634	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	3	55	theme	carp	505:508	arg1	carp					505:508	the grass carp serum IgM	495:518	the grass carp serum IgM	495:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	3	55	theme	carp	505:508	arg1	site					487:490	each glycosylation site	468:490	each glycosylation site of the grass carp serum IgM	468:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	1	56	theme	important	139:147	arg1	role					149:152	an important role	136:152	an important role	136:152	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	10	57	theme	processed	1647:1655	arg1	oligosaccharides					1657:1672	highly processed oligosaccharides	1640:1672	highly processed oligosaccharides attached to individual glycosites	1640:1706	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	6	58	theme	liquid	928:933	arg1	spectrometry					986:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	5	59	located	observed	775:782	arg1	IgM					795:797	dimeric IgM	787:797	dimeric IgM	787:797	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	5	59	located	observed	775:782	arg2	decrease					711:718	A striking decrease	700:718	A striking decrease in the level of occupancy at the Asn-565 glycosite	700:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	9	60	theme	overwhelming	1488:1499	arg1	majority					1501:1508	the overwhelming majority	1484:1508	the overwhelming majority of carbohydrates were of the complex-type	1484:1550	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30487799	8	61	theme	complex-type	1323:1334	arg1	glycans					1356:1362	complex-type and no high-mannose glycans	1323:1362	glycans	1356:1362	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	6	62	dep	carp	1189:1192	arg1	IgM					1200:1202	serum IgM	1194:1202	grass carp serum IgM	1183:1202	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	10	63	theme	individual	1686:1695	arg1	glycosites					1697:1706	individual glycosites	1686:1706	individual glycosites	1686:1706	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	3	64	theme	glycosylation	473:485	arg1	carp					505:508	the grass carp serum IgM	495:518	the grass carp serum IgM	495:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	3	64	theme	glycosylation	473:485	arg1	site					487:490	each glycosylation site	468:490	each glycosylation site of the grass carp serum IgM	468:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	3	65	dep	carp	505:508	arg1	IgM					516:518	serum IgM	510:518	the grass carp serum IgM	495:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	8	66	theme	other	1293:1297	arg1	species					1299:1305	other species	1293:1305	other species	1293:1305	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	4	67	gly	glycosylation	536:548	arg2	sites					550:554	the four glycosylation sites	527:554	the four glycosylation sites	527:554	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	4	67	gly	glycosylation	536:548	arg2	four					531:534	four	531:534	four	531:534	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	6	68	theme	complex-type	1015:1026	arg1	glycans					1028:1034	complex-type glycans	1015:1034	complex-type glycans with substantial heterogeneity	1015:1065	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	2	69	link	N-linked	188:195	arg1	carbohydrates					197:209	The N-linked carbohydrates	184:209	The N-linked carbohydrates presenting on IgM	184:227	The N-linked carbohydrates presenting on IgM have been well documented in higher vertebrates, but little is known regarding site-specific N-glycan characteristics in teleost IgM.
30487799	5	70	from	level	727:731	arg1	glycosite					761:769	the Asn-565 glycosite	749:769	the Asn-565 glycosite	749:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	1	71	theme	adaptive	165:172	arg1	immunity					174:181	humoral adaptive immunity	157:181	humoral adaptive immunity	157:181	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	7	72	theme	single	1227:1232	arg1	site					1234:1237	a single site	1225:1237	a single site	1225:1237	Glycan variation at a single site was greatest at the Asn-262 glycosite.
30487799	5	73	from	glycosite	761:769	arg1	level					727:731	the level	723:731	the level of occupancy at the Asn-565 glycosite	723:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	5	73	from	glycosite	761:769	arg1	occupancy					736:744	occupancy	736:744	occupancy at the Asn-565 glycosite	736:769	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	5	74	theme	glycan	841:846	arg1	occupancy					848:856	no glycan occupancy	838:856	no glycan occupancy of Asn-565	838:867	A striking decrease in the level of occupancy at the Asn-565 glycosite was observed in dimeric IgM compared to that in monomeric IgM, and no glycan occupancy of Asn-565 was observed in tetrameric IgM.
30487799	6	75	theme	mass	981:984	arg1	spectrometry					986:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	4	76	theme	C-terminal	652:661	arg1	tailpiece					663:671	the C-terminal tailpiece	648:671	the C-terminal tailpiece	648:671	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	6	77	theme	ionization	963:972	arg1	spectrometry					986:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	liquid chromatography-electrospray ionization tandem mass spectrometry	928:997	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	8	78	theme	no	1340:1341	arg1	glycans					1356:1362	complex-type and no high-mannose glycans	1323:1362	glycans	1356:1362	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	7	79	theme	Glycan	1205:1210	arg1	variation					1212:1220	Glycan variation	1205:1220	Glycan variation at a single site	1205:1237	Glycan variation at a single site was greatest at the Asn-262 glycosite.
30487799	8	80	theme	glycans	1356:1362	arg1	traces					1313:1318	only traces	1308:1318	only traces of complex-type and no high-mannose glycans	1308:1362	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	0	81	theme	N-Glycan	14:21	arg1	Characterization					23:38	Site-Specific N-Glycan Characterization	0:38	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.	0:63	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.
30487799	8	82	from	IgMs	1285:1288	arg1	species					1299:1305	other species	1293:1305	other species	1293:1305	Unlike IgMs in other species, only traces of complex-type and no high-mannose glycans were found at the Asn-565 glycosite.
30487799	7	83	gly	glycosite	1267:1275	arg2	glycosite					1267:1275	the Asn-262 glycosite	1255:1275	the Asn-262 glycosite	1255:1275	Glycan variation at a single site was greatest at the Asn-262 glycosite.
30487799	1	84	from	antibody	101:108	arg1	fish					121:124	teleost fish	113:124	teleost fish	113:124	Immunoglobulin M (IgM) is the major antibody in teleost fish and plays an important role in humoral adaptive immunity.
30487799	4	85	theme	glycosylation	536:548	arg1	sites					550:554	the four glycosylation sites	527:554	the four glycosylation sites	527:554	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	6	86	dep	neutral	1073:1079	arg1	non-fucosyl-oligosaccharides					1140:1167	non-fucosyl-oligosaccharides	1140:1167	non-fucosyl-oligosaccharides	1140:1167	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	0	87	theme	Carp	49:52	arg1	IgM					60:62	Grass Carp Serum IgM	43:62	Grass Carp Serum IgM	43:62	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.
30487799	0	88	theme	IgM	60:62	arg1	Characterization					23:38	Site-Specific N-Glycan Characterization	0:38	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.	0:63	Site-Specific N-Glycan Characterization of Grass Carp Serum IgM.
30487799	2	89	theme	site-specific	308:320	arg1	characteristics					331:345	site-specific N-glycan characteristics	308:345	site-specific N-glycan characteristics	308:345	The N-linked carbohydrates presenting on IgM have been well documented in higher vertebrates, but little is known regarding site-specific N-glycan characteristics in teleost IgM.
30487799	6	90	with	glycans	1028:1034	arg1	heterogeneity					1053:1065	substantial heterogeneity	1041:1065	substantial heterogeneity	1041:1065	Glycopeptide analysis with liquid chromatography-electrospray ionization tandem mass spectrometry revealed mainly complex-type glycans with substantial heterogeneity, with neutral; monosialyl-, disialyl- and trisialylated; and fucosyl-and non-fucosyl-oligosaccharides conjugated to grass carp serum IgM.
30487799	3	91	theme	grass	499:503	arg1	carp					505:508	the grass carp serum IgM	495:518	the grass carp serum IgM	495:518	In order to characterize these site-specific N-glycans, we conducted the first study of the N-glycans of each glycosylation site of the grass carp serum IgM.
30487799	7	92	theme	Asn-262	1259:1265	arg1	glycosite					1267:1275	the Asn-262 glycosite	1255:1275	the Asn-262 glycosite	1255:1275	Glycan variation at a single site was greatest at the Asn-262 glycosite.
30487799	10	93	theme	carp	1587:1590	arg1	IgM					1598:1600	grass carp serum IgM	1581:1600	grass carp serum IgM	1581:1600	These results indicate that grass carp serum IgM exhibits unique N-glycan features and highly processed oligosaccharides attached to individual glycosites.
30487799	2	94	theme	teleost	350:356	arg1	IgM					358:360	teleost IgM	350:360	teleost IgM	350:360	The N-linked carbohydrates presenting on IgM have been well documented in higher vertebrates, but little is known regarding site-specific N-glycan characteristics in teleost IgM.
30487799	4	95	from	tailpiece	663:671	arg1	Asn-565					637:643	Asn-565	637:643	Asn-565 at the C-terminal tailpiece	637:671	Among the four glycosylation sites, the Asn-262, Asn-303, and Asn-426 residues were efficiently glycosylated, while Asn-565 at the C-terminal tailpiece was incompletely occupied.
30487799	9	96	theme	laser	1417:1421	arg1	ionization					1434:1443	Matrix-assisted laser desorption ionization	1401:1443	Matrix-assisted laser desorption ionization analysis of released glycans	1401:1472	Matrix-assisted laser desorption ionization analysis of released glycans confirmed the overwhelming majority of carbohydrates were of the complex-type.
30308090	7	0	from	non-raft	1466:1473	arg1	translocation					1439:1451	reduced translocation	1431:1451	reduced translocation of Trkβ from non-raft to raft regions	1431:1489	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	2	1	theme	molecular	386:394	arg1	events					396:401	The molecular events	382:401	The molecular events promoting BDNF-mediated pro-death signalling in hypoxia	382:457	The molecular events promoting BDNF-mediated pro-death signalling in hypoxia, however, still remain an enigma.
30308090	5	2	from	calnexin	1057:1064	arg1	morphology					1107:1116	the endoplasmic reticulum morphology	1081:1116	the endoplasmic reticulum morphology	1081:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	0	3	from	neurodegeneration	101:117	arg1	hippocampus					122:132	hippocampus	122:132	hippocampus	122:132	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	9	4	theme	receptor-mediated	1820:1836	arg1	signalling					1844:1853	p75 receptor-mediated death signalling	1816:1853	p75 receptor-mediated death signalling in hippocampal neurons	1816:1876	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	6	5	from	expression	1148:1157	arg1	rafts					1178:1182	lipid rafts	1172:1182	lipid rafts	1172:1182	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	6	5	from	expression	1148:1157	arg1	regions					1255:1261	non-raft regions	1246:1261	non-raft regions following hypoxic exposure	1246:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	3	6	theme	isoforms	588:595	arg1	alteration					569:578	alteration	569:578	alteration of BDNF isoforms	569:595	This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia.
30308090	5	7	theme	increased	955:963	arg1	expression					965:974	increased expression	955:974	increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology	955:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	6	8	theme	non-raft	1246:1253	arg1	regions					1255:1261	non-raft regions	1246:1261	non-raft regions following hypoxic exposure	1246:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	1	9	theme	neuronal	211:218	arg1	survivability					220:232	neuronal survivability	211:232	neuronal survivability	211:232	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	9	10	theme	hippocampal	1858:1868	arg1	neurons					1870:1876	hippocampal neurons	1858:1876	hippocampal neurons	1858:1876	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	6	11	theme	higher	1188:1193	arg1	expression					1195:1204	higher expression	1188:1204	higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure	1188:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	8	12	theme	cholesterol	1571:1581	arg1	oxidation					1583:1591	cholesterol oxidation	1571:1591	cholesterol oxidation	1571:1591	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	4	13	theme	global	714:719	arg1	hypoxia					731:737	global hypobaric hypoxia	714:737	global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity	714:807	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	1	14	theme	neurotrophic	149:160	arg1	factor					162:167	Brain-derived neurotrophic factor	135:167	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity	135:273	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	1	14	theme	neurotrophic	149:160	arg1	BDNF					170:173	BDNF	170:173	BDNF	170:173	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	5	15	link	N-linked	906:913	arg1	glycosylation					915:927	N-linked glycosylation	906:927	N-linked glycosylation	906:927	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	7	16	from	decline	1346:1352	arg1	fluidity					1366:1373	membrane fluidity	1357:1373	membrane fluidity	1357:1373	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	7	17	theme	reduced	1431:1437	arg1	translocation					1439:1451	reduced translocation	1431:1451	reduced translocation of Trkβ from non-raft to raft regions	1431:1489	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	8	18	from	non-raft	1634:1641	arg1	oxidation					1583:1591	cholesterol oxidation	1571:1591	cholesterol oxidation	1571:1591	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	8	18	from	non-raft	1634:1641	arg1	translocation					1607:1619	increased translocation	1597:1619	increased translocation of Trkβ from non-raft to raft regions	1597:1657	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	5	19	theme	reticulum	991:999	arg1	markers					1008:1014	endoplasmic reticulum stress markers	979:1014	endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology	979:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	19	theme	reticulum	991:999	arg1	viz.					1016:1019	viz.	1016:1019	viz.	1016:1019	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	19	theme	reticulum	991:999	arg1	calnexin					1057:1064	calnexin	1057:1064	calnexin	1057:1064	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	19	theme	reticulum	991:999	arg1	protein					1040:1046	glucose-regulated protein	1022:1046	glucose-regulated protein (Grp78)	1022:1054	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	20	theme	markers	1008:1014	arg1	expression					965:974	increased expression	955:974	increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology	955:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	8	21	theme	raft	1646:1649	arg1	regions					1651:1657	raft regions	1646:1657	raft regions	1646:1657	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	5	22	theme	Chronic	810:816	arg1	exposure					826:833	Chronic hypoxic exposure	810:833	Chronic hypoxic exposure for 7 days	810:844	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	6	23	from	regions	1255:1261	arg1	expression					1148:1157	enriched expression	1139:1157	enriched expression of p75NTR in lipid rafts	1139:1182	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	6	23	from	regions	1255:1261	arg1	expression					1195:1204	higher expression	1188:1204	higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure	1188:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	7	24	theme	Further	1291:1297	arg1	investigations					1299:1312	Further investigations	1291:1312	Further investigations on membrane properties	1291:1335	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	9	25	from	alteration	1770:1779	arg1	dynamics					1789:1796	raft dynamics	1784:1796	raft dynamics	1784:1796	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	8	26	theme	neuronal	1672:1679	arg1	survival					1681:1688	neuronal survival	1672:1688	neuronal survival	1672:1688	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	0	27	theme	Hypoxia-mediated	0:15	arg1	alteration					17:26	Hypoxia-mediated alteration	0:26	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics	0:69	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	8	28	theme	Trkβ	1624:1627	arg1	oxidation					1583:1591	cholesterol oxidation	1571:1591	cholesterol oxidation	1571:1591	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	8	28	theme	Trkβ	1624:1627	arg1	translocation					1607:1619	increased translocation	1597:1619	increased translocation of Trkβ from non-raft to raft regions	1597:1657	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	5	29	from	viz.	1016:1019	arg1	morphology					1107:1116	the endoplasmic reticulum morphology	1081:1116	the endoplasmic reticulum morphology	1081:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	7	30	theme	Trkβ	1456:1459	arg1	translocation					1439:1451	reduced translocation	1431:1451	reduced translocation of Trkβ from non-raft to raft regions	1431:1489	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	8	31	theme	E	1519:1519	arg1	Supplementation					1492:1506	Supplementation	1492:1506	Supplementation of vitamin E during hypoxic exposure on the other hand	1492:1561	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	3	32	from	neurodegeneration	642:658	arg1	hypoxia					663:669	hypoxia	663:669	hypoxia	663:669	This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia.
30308090	5	33	theme	N-linked	906:913	arg1	glycosylation					915:927	N-linked glycosylation	906:927	N-linked glycosylation	906:927	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	9	34	theme	novel	1721:1725	arg1	mechanism					1727:1735	a novel mechanism	1719:1735	a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia	1719:1899	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	9	35	from	mechanism	1727:1735	arg1	dynamics					1789:1796	raft dynamics	1784:1796	raft dynamics	1784:1796	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	8	36	theme	hypoxic	1528:1534	arg1	exposure					1536:1543	hypoxic exposure	1528:1543	hypoxic exposure on the other hand	1528:1561	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	1	37	theme	p75	345:347	arg1	p75NTR					373:378	p75NTR	373:378	p75NTR	373:378	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	1	37	theme	p75	345:347	arg1	receptors					362:370	its p75 Neurotrophin receptors	341:370	its p75 Neurotrophin receptors (p75NTR)	341:379	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	2	38	from	signalling	437:446	arg1	hypoxia					451:457	hypoxia	451:457	hypoxia	451:457	The molecular events promoting BDNF-mediated pro-death signalling in hypoxia, however, still remain an enigma.
30308090	6	39	theme	enriched	1139:1146	arg1	expression					1148:1157	enriched expression	1139:1157	enriched expression of p75NTR in lipid rafts	1139:1182	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	3	40	theme	signalling	537:546	arg1	cascades					548:555	the signalling cascades	533:555	the signalling cascades involved in alteration of BDNF isoforms	533:595	This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia.
30308090	5	41	theme	pro-BDNF	879:886	arg1	alteration					892:901	alteration	892:901	alteration in N-linked glycosylation	892:927	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	41	theme	pro-BDNF	879:886	arg1	expression					865:874	higher expression	858:874	higher expression of pro-BDNF	858:886	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	9	42	theme	oxidation-induced	1752:1768	arg1	alteration					1770:1779	cholesterol oxidation-induced alteration	1740:1779	cholesterol oxidation-induced alteration in raft dynamics	1740:1796	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	1	43	link	Brain-derived	135:147	arg1	factor					162:167	Brain-derived neurotrophic factor	135:167	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity	135:273	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	1	43	link	Brain-derived	135:147	arg1	BDNF					170:173	BDNF	170:173	BDNF	170:173	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	8	44	theme	other	1552:1556	arg1	hand					1558:1561	the other hand	1548:1561	the other hand	1548:1561	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	1	45	theme	synaptic	255:262	arg1	plasticity					264:273	synaptic plasticity	255:273	synaptic plasticity	255:273	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	5	46	theme	endoplasmic	1085:1095	arg1	reticulum					1097:1105	the endoplasmic reticulum	1081:1105	the endoplasmic reticulum morphology	1081:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	6	47	theme	receptor	1218:1225	arg1	kinase					1227:1232	tyrosine receptor kinase β	1209:1234	tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure	1209:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	6	47	theme	receptor	1218:1225	arg1	Trkβ					1237:1240	Trkβ	1237:1240	Trkβ	1237:1240	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	2	48	theme	BDNF-mediated	413:425	arg1	signalling					437:446	BDNF-mediated pro-death signalling	413:446	BDNF-mediated pro-death signalling in hypoxia	413:457	The molecular events promoting BDNF-mediated pro-death signalling in hypoxia, however, still remain an enigma.
30308090	4	49	theme	Sprague-Dawley	678:691	arg1	rats					693:696	Adult Sprague-Dawley rats	672:696	Adult Sprague-Dawley rats	672:696	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	7	50	theme	membrane	1357:1364	arg1	fluidity					1366:1373	membrane fluidity	1357:1373	membrane fluidity	1357:1373	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	6	51	theme	hypoxic	1273:1279	arg1	exposure					1281:1288	hypoxic exposure	1273:1288	hypoxic exposure	1273:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	3	52	theme	BDNF	583:586	arg1	isoforms					588:595	BDNF isoforms	583:595	BDNF isoforms	583:595	This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia.
30308090	8	53	from	exposure	1536:1543	arg1	hand					1558:1561	the other hand	1548:1561	the other hand	1548:1561	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	0	54	theme	raft	57:60	arg1	dynamics					62:69	raft dynamics	57:69	raft dynamics	57:69	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	9	55	theme	death	1838:1842	arg1	signalling					1844:1853	p75 receptor-mediated death signalling	1816:1853	p75 receptor-mediated death signalling in hippocampal neurons	1816:1876	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	4	56	theme	hypobaric	721:729	arg1	hypoxia					731:737	global hypobaric hypoxia	714:737	global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity	714:807	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	9	57	from	signalling	1844:1853	arg1	neurons					1870:1876	hippocampal neurons	1858:1876	hippocampal neurons	1858:1876	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	3	58	theme	cognate	605:611	arg1	subtypes					622:629	its cognate receptor subtypes	601:629	its cognate receptor subtypes	601:629	This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia.
30308090	9	59	theme	chronic	1885:1891	arg1	hypoxia					1893:1899	chronic hypoxia	1885:1899	chronic hypoxia	1885:1899	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	8	60	theme	increased	1597:1605	arg1	translocation					1607:1619	increased translocation	1597:1619	increased translocation of Trkβ from non-raft to raft regions	1597:1657	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	1	61	theme	Brain-derived	135:147	arg1	factor					162:167	Brain-derived neurotrophic factor	135:167	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity	135:273	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	1	61	theme	Brain-derived	135:147	arg1	BDNF					170:173	BDNF	170:173	BDNF	170:173	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	4	62	theme	standard	775:782	arg1	temperature					784:794	standard temperature	775:794	standard temperature	775:794	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	5	63	theme	glucose-regulated	1022:1038	arg1	markers					1008:1014	endoplasmic reticulum stress markers	979:1014	endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology	979:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	63	theme	glucose-regulated	1022:1038	arg1	Grp78					1049:1053	Grp78	1049:1053	Grp78	1049:1053	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	63	theme	glucose-regulated	1022:1038	arg1	protein					1040:1046	glucose-regulated protein	1022:1046	glucose-regulated protein (Grp78)	1022:1054	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	0	64	theme	BDNF	81:84	arg1	signalling					86:95	BDNF signalling	81:95	BDNF signalling	81:95	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	5	65	theme	endoplasmic	979:989	arg1	reticulum					991:999	endoplasmic reticulum	979:999	endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology	979:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	7	66	theme	raft	1478:1481	arg1	regions					1483:1489	raft regions	1478:1489	raft regions	1478:1489	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	7	67	theme	membrane	1317:1324	arg1	properties					1326:1335	membrane properties	1317:1335	membrane properties	1317:1335	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	5	68	theme	stress	1001:1006	arg1	markers					1008:1014	endoplasmic reticulum stress markers	979:1014	endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology	979:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	68	theme	stress	1001:1006	arg1	viz.					1016:1019	viz.	1016:1019	viz.	1016:1019	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	68	theme	stress	1001:1006	arg1	calnexin					1057:1064	calnexin	1057:1064	calnexin	1057:1064	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	68	theme	stress	1001:1006	arg1	protein					1040:1046	glucose-regulated protein	1022:1046	glucose-regulated protein (Grp78)	1022:1054	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	0	69	from	alteration	17:26	arg1	oxidation					43:51	cholesterol oxidation	31:51	cholesterol oxidation	31:51	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	0	69	from	alteration	17:26	arg1	dynamics					62:69	raft dynamics	57:69	raft dynamics	57:69	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	4	70	theme	7620 m	765:770	arg1	altitude					753:760	an altitude	750:760	an altitude of 7620 m at standard temperature and humidity	750:807	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	5	71	from	expression	865:874	arg1	hippocampus					932:942	hippocampus	932:942	hippocampus	932:942	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	71	from	expression	865:874	arg1	glycosylation					915:927	N-linked glycosylation	906:927	N-linked glycosylation	906:927	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	3	72	theme	receptor	613:620	arg1	subtypes					622:629	its cognate receptor subtypes	601:629	its cognate receptor subtypes	601:629	This study attempts towards deciphering the signalling cascades involved in alteration of BDNF isoforms and its cognate receptor subtypes leading to neurodegeneration in hypoxia.
30308090	7	73	theme	increased	1386:1394	arg1	oxidation					1408:1416	increased cholesterol oxidation	1386:1416	increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions	1386:1489	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	5	74	theme	hypoxic	818:824	arg1	exposure					826:833	Chronic hypoxic exposure	810:833	Chronic hypoxic exposure for 7 days	810:844	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	9	75	from	dynamics	1789:1796	arg1	mechanism					1727:1735	a novel mechanism	1719:1735	a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia	1719:1899	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	5	76	from	alteration	892:901	arg1	hippocampus					932:942	hippocampus	932:942	hippocampus	932:942	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	76	from	alteration	892:901	arg1	glycosylation					915:927	N-linked glycosylation	906:927	N-linked glycosylation	906:927	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	77	from	protein	1040:1046	arg1	morphology					1107:1116	the endoplasmic reticulum morphology	1081:1116	the endoplasmic reticulum morphology	1081:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	6	78	theme	lipid	1172:1176	arg1	rafts					1178:1182	lipid rafts	1172:1182	lipid rafts	1172:1182	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	5	79	dep	markers	1008:1014	arg1	calnexin					1057:1064	calnexin	1057:1064	calnexin	1057:1064	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	79	dep	markers	1008:1014	arg1	protein					1040:1046	glucose-regulated protein	1022:1046	glucose-regulated protein (Grp78)	1022:1054	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	79	dep	markers	1008:1014	arg1	changes					1070:1076	changes	1070:1076	changes in the endoplasmic reticulum morphology	1070:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	79	dep	markers	1008:1014	arg1	markers					1008:1014	endoplasmic reticulum stress markers	979:1014	endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology	979:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	79	dep	markers	1008:1014	arg1	Grp78					1049:1053	Grp78	1049:1053	Grp78	1049:1053	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	5	79	dep	markers	1008:1014	arg1	viz.					1016:1019	viz.	1016:1019	viz.	1016:1019	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	2	80	theme	pro-death	427:435	arg1	signalling					437:446	BDNF-mediated pro-death signalling	413:446	BDNF-mediated pro-death signalling in hypoxia	413:457	The molecular events promoting BDNF-mediated pro-death signalling in hypoxia, however, still remain an enigma.
30308090	0	81	theme	cholesterol	31:41	arg1	oxidation					43:51	cholesterol oxidation	31:51	cholesterol oxidation	31:51	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	9	82	theme	raft	1784:1787	arg1	dynamics					1789:1796	raft dynamics	1784:1796	raft dynamics	1784:1796	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	6	83	theme	p75NTR	1162:1167	arg1	expression					1148:1157	enriched expression	1139:1157	enriched expression of p75NTR in lipid rafts	1139:1182	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	6	83	theme	p75NTR	1162:1167	arg1	expression					1195:1204	higher expression	1188:1204	higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure	1188:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	8	84	theme	vitamin	1511:1517	arg1	E					1519:1519	vitamin E	1511:1519	vitamin E	1511:1519	Supplementation of vitamin E during hypoxic exposure on the other hand reduced cholesterol oxidation and increased translocation of Trkβ from non-raft to raft regions and promoted neuronal survival.
30308090	6	85	theme	tyrosine	1209:1216	arg1	kinase					1227:1232	tyrosine receptor kinase β	1209:1234	tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure	1209:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	6	85	theme	tyrosine	1209:1216	arg1	Trkβ					1237:1240	Trkβ	1237:1240	Trkβ	1237:1240	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	5	86	theme	higher	858:863	arg1	expression					865:874	higher expression	858:874	higher expression of pro-BDNF	858:886	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	6	87	from	kinase	1227:1232	arg1	regions					1255:1261	non-raft regions	1246:1261	non-raft regions following hypoxic exposure	1246:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	1	88	theme	Neurotrophin	349:360	arg1	p75NTR					373:378	p75NTR	373:378	p75NTR	373:378	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	1	88	theme	Neurotrophin	349:360	arg1	receptors					362:370	its p75 Neurotrophin receptors	341:370	its p75 Neurotrophin receptors (p75NTR)	341:379	Brain-derived neurotrophic factor (BDNF) which is primarily associated with neuronal survivability, differentiation and synaptic plasticity has been reported to mediate neurodegeneration in hypoxia through its p75 Neurotrophin receptors (p75NTR).
30308090	9	89	theme	cholesterol	1740:1750	arg1	alteration					1770:1779	cholesterol oxidation-induced alteration	1740:1779	cholesterol oxidation-induced alteration in raft dynamics	1740:1796	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	7	90	theme	cholesterol	1396:1406	arg1	oxidation					1408:1416	increased cholesterol oxidation	1386:1416	increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions	1386:1489	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	7	91	from	investigations	1299:1312	arg1	properties					1326:1335	membrane properties	1317:1335	membrane properties	1317:1335	Further investigations on membrane properties revealed decline in membrane fluidity along with increased cholesterol oxidation resulting in reduced translocation of Trkβ from non-raft to raft regions.
30308090	4	92	from	humidity	800:807	arg1	altitude					753:760	an altitude	750:760	an altitude of 7620 m at standard temperature and humidity	750:807	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	9	93	theme	alteration	1770:1779	arg1	mechanism					1727:1735	a novel mechanism	1719:1735	a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia	1719:1899	Hence, our findings suggest a novel mechanism of cholesterol oxidation-induced alteration in raft dynamics which is promotes p75 receptor-mediated death signalling in hippocampal neurons during chronic hypoxia.
30308090	6	94	theme	kinase	1227:1232	arg1	expression					1148:1157	enriched expression	1139:1157	enriched expression of p75NTR in lipid rafts	1139:1182	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	6	94	theme	kinase	1227:1232	arg1	expression					1195:1204	higher expression	1188:1204	higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure	1188:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	4	95	theme	Adult	672:676	arg1	rats					693:696	Adult Sprague-Dawley rats	672:696	Adult Sprague-Dawley rats	672:696	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	6	96	from	expression	1195:1204	arg1	rafts					1178:1182	lipid rafts	1172:1182	lipid rafts	1172:1182	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	6	96	from	expression	1195:1204	arg1	regions					1255:1261	non-raft regions	1246:1261	non-raft regions following hypoxic exposure	1246:1288	Our findings reveal enriched expression of p75NTR in lipid rafts and higher expression of tyrosine receptor kinase β (Trkβ) in non-raft regions following hypoxic exposure.
30308090	4	97	from	temperature	784:794	arg1	altitude					753:760	an altitude	750:760	an altitude of 7620 m at standard temperature and humidity	750:807	Adult Sprague-Dawley rats were exposed to global hypobaric hypoxia simulating an altitude of 7620 m at standard temperature and humidity.
30308090	5	98	theme	reticulum	1097:1105	arg1	morphology					1107:1116	the endoplasmic reticulum morphology	1081:1116	the endoplasmic reticulum morphology	1081:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
30308090	0	99	from	signalling	86:95	arg1	hippocampus					122:132	hippocampus	122:132	hippocampus	122:132	Hypoxia-mediated alteration in cholesterol oxidation and raft dynamics regulates BDNF signalling and neurodegeneration in hippocampus.
30308090	5	100	from	changes	1070:1076	arg1	morphology					1107:1116	the endoplasmic reticulum morphology	1081:1116	the endoplasmic reticulum morphology	1081:1116	Chronic hypoxic exposure for 7 days resulted in higher expression of pro-BDNF and alteration in N-linked glycosylation in hippocampus along with increased expression of endoplasmic reticulum stress markers viz., glucose-regulated protein (Grp78), calnexin and changes in the endoplasmic reticulum morphology.
29969180	4	0	theme	proteins	1121:1128	arg1	analysis					1098:1105	mass spectrometry-based N-glycan analysis	1065:1105	mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12	1065:1173	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	4	0	theme	proteins	1121:1128	arg1	sequencing					1050:1059	Sanger sequencing	1043:1059	Sanger sequencing	1043:1059	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	5	1	theme	hamster	1331:1337	arg1	CHO					1346:1348	CHO	1346:1348	CHO	1346:1348	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	5	1	theme	hamster	1331:1337	arg1	ovary					1339:1343	Chinese hamster ovary	1323:1343	Chinese hamster ovary (CHO)	1323:1349	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	2	2	theme	N-glycosylation	648:662	arg1	machinery					664:672	the endogenous N-glycosylation machinery	633:672	the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose	633:759	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	5	3	theme	line	1313:1316	arg1	cells					1351:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	5	4	theme	glycovariants	1235:1247	arg1	affinity					1218:1225	the CD64-binding affinity	1201:1225	the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1201:1355	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	1	5	theme	proteins	282:289	arg1	production					253:262	the production	249:262	the production of pharmaceutical proteins	249:289	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	3	6	from	activity	939:946	arg1	deficient					857:865	deficient	857:865	deficient	857:865	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	0	7	from	knockout	21:28	arg1	benthamiana					76:86	Nicotiana benthamiana	66:86	Nicotiana benthamiana for the production of recombinant proteins	66:129	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	2	8	theme	endogenous	637:646	arg1	machinery					664:672	the endogenous N-glycosylation machinery	633:672	the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose	633:759	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	2	9	theme	N-glycans	708:716	arg1	synthesis					687:695	the synthesis	683:695	the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose	683:759	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	1	10	theme	fast	188:191	arg1	platforms					235:243	fast, flexible and easily scalable alternative platforms	188:243	fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins	188:289	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	3	11	theme	different	980:988	arg1	genes					990:994	six different genes	976:994	six different genes	976:994	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	5	12	theme	CD64-binding	1205:1216	arg1	affinity					1218:1225	the CD64-binding affinity	1201:1225	the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1201:1355	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	0	13	theme	recombinant	110:120	arg1	proteins					122:129	recombinant proteins	110:129	recombinant proteins	110:129	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	1	14	theme	β-1,2-xylose	380:391	arg1	residues					415:422	β-1,2-xylose and core α-1,3-fucose residues	380:422	residues	415:422	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	2	15	theme	complex	700:706	arg1	N-glycans					708:716	complex N-glycans	700:716	complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose	700:759	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	3	16	theme	genes	990:994	arg1	mutation					964:971	the mutation	960:971	the mutation of six different genes	960:994	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	3	17	theme	β-1,2-xylosyltransferase	914:937	arg1	activity					939:946	β-1,2-xylosyltransferase activity	914:946	β-1,2-xylosyltransferase activity	914:946	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	2	18	theme	transient	559:567	arg1	expression					569:578	the transient expression	555:578	the transient expression of recombinant proteins	555:602	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	3	19	theme	multiplex	776:784	arg1	editing					805:811	multiplex CRISPR/Cas9 genome editing	776:811	multiplex CRISPR/Cas9 genome editing	776:811	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	3	20	from	deficient	857:865	arg1	α-1,3-fucosyltransferase					885:908	plant-specific α-1,3-fucosyltransferase	870:908	plant-specific α-1,3-fucosyltransferase	870:908	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	3	20	from	deficient	857:865	arg1	activity					939:946	β-1,2-xylosyltransferase activity	914:946	β-1,2-xylosyltransferase activity	914:946	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	4	21	theme	recombinant	1138:1148	arg1	antibody					1161:1168	the recombinant monoclonal antibody 2G12	1134:1173	the recombinant monoclonal antibody 2G12	1134:1173	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	4	22	theme	N-glycan	1089:1096	arg1	analysis					1098:1105	mass spectrometry-based N-glycan analysis	1065:1105	mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12	1065:1173	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	1	23	theme	core	397:400	arg1	residues					415:422	β-1,2-xylose and core α-1,3-fucose residues	380:422	residues	415:422	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	3	24	used	used	771:774	arg2	we					768:769	we	768:769	we	768:769	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	0	25	theme	proteins	122:129	arg1	production					96:105	the production	92:105	the production of recombinant proteins	92:129	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	1	26	theme	α-1,3-fucose	402:413	arg1	residues					415:422	β-1,2-xylose and core α-1,3-fucose residues	380:422	residues	415:422	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	2	27	theme	Nicotiana	514:522	arg1	benthamiana					524:534	Nicotiana benthamiana	514:534	Nicotiana benthamiana	514:534	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	1	28	theme	plant-derived	490:502	arg1	proteins					504:511	plant-derived proteins	490:511	plant-derived proteins	490:511	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	4	29	theme	antibody	1161:1168	arg1	analysis					1098:1105	mass spectrometry-based N-glycan analysis	1065:1105	mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12	1065:1173	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	4	29	theme	antibody	1161:1168	arg1	sequencing					1050:1059	Sanger sequencing	1043:1059	Sanger sequencing	1043:1059	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	1	30	theme	flexible	194:201	arg1	platforms					235:243	fast, flexible and easily scalable alternative platforms	188:243	fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins	188:289	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	31	theme	residues	415:422	arg1	presence					368:375	the presence	364:375	the presence of β-1,2-xylose and core α-1,3-fucose residues in plants	364:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	5	32	theme	Chinese	1323:1329	arg1	CHO					1346:1348	CHO	1346:1348	CHO	1346:1348	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	5	32	theme	Chinese	1323:1329	arg1	ovary					1339:1343	Chinese hamster ovary	1323:1343	Chinese hamster ovary (CHO)	1323:1349	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	1	33	theme	proteins	504:511	arg1	immunogenicity					472:485	immunogenicity	472:485	immunogenicity	472:485	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	33	theme	proteins	504:511	arg1	potency					460:466	potency	460:466	potency	460:466	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	33	theme	proteins	504:511	arg1	activity					450:457	the activity	446:457	the activity	446:457	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	3	34	theme	CRISPR/Cas9	786:796	arg1	editing					805:811	multiplex CRISPR/Cas9 genome editing	776:811	multiplex CRISPR/Cas9 genome editing	776:811	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	1	35	from	residues	415:422	arg1	plants					427:432	plants	427:432	plants	427:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	36	theme	plant	316:320	arg1	glycans					345:351	plant and mammalian N-linked glycans	316:351	glycans	345:351	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	36	theme	plant	316:320	arg1	presence					368:375	the presence	364:375	the presence of β-1,2-xylose and core α-1,3-fucose residues in plants	364:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	37	theme	scalable	214:221	arg1	platforms					235:243	fast, flexible and easily scalable alternative platforms	188:243	fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins	188:289	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	3	38	theme	genome	798:803	arg1	editing					805:811	multiplex CRISPR/Cas9 genome editing	776:811	multiplex CRISPR/Cas9 genome editing	776:811	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	2	39	theme	proteins	595:602	arg1	expression					569:578	the transient expression	555:578	the transient expression of recombinant proteins	555:602	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	4	40	theme	Sanger	1043:1048	arg1	sequencing					1050:1059	Sanger sequencing	1043:1059	Sanger sequencing	1043:1059	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	1	41	theme	alternative	223:233	arg1	platforms					235:243	fast, flexible and easily scalable alternative platforms	188:243	fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins	188:289	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	0	42	theme	genes	57:61	arg1	knockout					21:28	knockout	21:28	knockout	21:28	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	1	43	theme	mammalian	326:334	arg1	glycans					345:351	plant and mammalian N-linked glycans	316:351	glycans	345:351	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	43	theme	mammalian	326:334	arg1	presence					368:375	the presence	364:375	the presence of β-1,2-xylose and core α-1,3-fucose residues in plants	364:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	2	44	theme	recombinant	583:593	arg1	proteins					595:602	recombinant proteins	583:602	recombinant proteins	583:602	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	0	45	theme	glycosyltransferase	37:55	arg1	genes					57:61	six glycosyltransferase genes	33:61	six glycosyltransferase genes	33:61	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	1	46	theme	N-linked	336:343	arg1	glycans					345:351	plant and mammalian N-linked glycans	316:351	glycans	345:351	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	46	theme	N-linked	336:343	arg1	presence					368:375	the presence	364:375	the presence of β-1,2-xylose and core α-1,3-fucose residues in plants	364:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	0	47	theme	core	156:159	arg1	α-1,3-fucose					161:172	core α-1,3-fucose	156:172	core α-1,3-fucose	156:172	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	5	48	theme	ovary	1339:1343	arg1	cells					1351:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	1	49	from	plants	427:432	arg1	presence					368:375	the presence	364:375	the presence of β-1,2-xylose and core α-1,3-fucose residues in plants	364:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	0	50	theme	Nicotiana	66:74	arg1	benthamiana					76:86	Nicotiana benthamiana	66:86	Nicotiana benthamiana for the production of recombinant proteins	66:129	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	3	51	theme	deficient	857:865	arg1	lines					851:855	N. benthamiana production lines	825:855	N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity	825:946	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	0	52	from	benthamiana	76:86	arg1	knockout					21:28	knockout	21:28	knockout	21:28	CRISPR/Cas9-mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β-1,2-xylose and core α-1,3-fucose.
29969180	4	53	theme	gene	1025:1028	arg1	knockouts					1030:1038	the functional gene knockouts	1010:1038	the functional gene knockouts	1010:1038	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	1	54	from	presence	368:375	arg1	plants					427:432	plants	427:432	plants	427:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	3	55	theme	N. benthamiana	825:838	arg1	lines					851:855	N. benthamiana production lines	825:855	N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity	825:946	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	5	56	theme	wild-type	1261:1269	arg1	cells					1351:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	1	57	link	N-linked	336:343	arg1	glycans					345:351	plant and mammalian N-linked glycans	316:351	glycans	345:351	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	1	57	link	N-linked	336:343	arg1	presence					368:375	the presence	364:375	the presence of β-1,2-xylose and core α-1,3-fucose residues in plants	364:432	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	5	58	theme	generated	1297:1305	arg1	line					1313:1316	the newly generated FX-KO line	1287:1316	the newly generated FX-KO line	1287:1316	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	3	59	theme	production	840:849	arg1	lines					851:855	N. benthamiana production lines	825:855	N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity	825:946	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	3	60	from	α-1,3-fucosyltransferase	885:908	arg1	deficient					857:865	deficient	857:865	deficient	857:865	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	2	61	theme	core	743:746	arg1	α-1,3-fucose					748:759	core α-1,3-fucose	743:759	core α-1,3-fucose	743:759	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	4	62	theme	endogenous	1110:1119	arg1	proteins					1121:1128	endogenous proteins	1110:1128	endogenous proteins	1110:1128	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	4	63	theme	functional	1014:1023	arg1	knockouts					1030:1038	the functional gene knockouts	1010:1038	the functional gene knockouts	1010:1038	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	5	64	theme	FX-KO	1307:1311	arg1	line					1313:1316	the newly generated FX-KO line	1287:1316	the newly generated FX-KO line	1287:1316	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	2	65	used	used	546:549	arg2	benthamiana					524:534	Nicotiana benthamiana	514:534	Nicotiana benthamiana	514:534	Nicotiana benthamiana is widely used for the transient expression of recombinant proteins so it is desirable to modify the endogenous N-glycosylation machinery to allow the synthesis of complex N-glycans lacking β-1,2-xylose and core α-1,3-fucose.
29969180	5	66	theme	CHO-produced	1429:1440	arg1	counterpart					1442:1452	its CHO-produced counterpart	1425:1452	its CHO-produced counterpart	1425:1452	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	1	67	link	plant-derived	490:502	arg1	proteins					504:511	plant-derived proteins	490:511	plant-derived proteins	490:511	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29969180	4	68	theme	monoclonal	1150:1159	arg1	antibody					1161:1168	the recombinant monoclonal antibody 2G12	1134:1173	the recombinant monoclonal antibody 2G12	1134:1173	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	5	69	theme	N. benthamiana	1271:1284	arg1	cells					1351:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells	1261:1355	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	3	70	theme	plant-specific	870:883	arg1	α-1,3-fucosyltransferase					885:908	plant-specific α-1,3-fucosyltransferase	870:908	plant-specific α-1,3-fucosyltransferase	870:908	Here, we used multiplex CRISPR/Cas9 genome editing to generate N. benthamiana production lines deficient in plant-specific α-1,3-fucosyltransferase and β-1,2-xylosyltransferase activity, reflecting the mutation of six different genes.
29969180	4	71	theme	spectrometry-based	1070:1087	arg1	analysis					1098:1105	mass spectrometry-based N-glycan analysis	1065:1105	mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12	1065:1173	We confirmed the functional gene knockouts by Sanger sequencing and mass spectrometry-based N-glycan analysis of endogenous proteins and the recombinant monoclonal antibody 2G12.
29969180	5	72	theme	glyco-engineered	1378:1393	arg1	antibody					1395:1402	the glyco-engineered antibody	1374:1402	the glyco-engineered antibody	1374:1402	Furthermore, we compared the CD64-binding affinity of 2G12 glycovariants produced in wild-type N. benthamiana, the newly generated FX-KO line, and Chinese hamster ovary (CHO) cells, confirming that the glyco-engineered antibody performed as well as its CHO-produced counterpart.
29969180	1	73	theme	pharmaceutical	267:280	arg1	proteins					282:289	pharmaceutical proteins	267:289	pharmaceutical proteins	267:289	Plants offer fast, flexible and easily scalable alternative platforms for the production of pharmaceutical proteins, but differences between plant and mammalian N-linked glycans, including the presence of β-1,2-xylose and core α-1,3-fucose residues in plants, can affect the activity, potency and immunogenicity of plant-derived proteins.
29864502	6	0	from	substitutions	1021:1033	arg1	epitopes					1042:1049	the epitopes	1038:1049	the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1038:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	2	1	theme	G14P[12	312:318	arg1	prevalent					349:357	prevalent	349:357	prevalent	349:357	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	2	1	theme	G14P[12	312:318	arg1	G3P[12					300:305	The G3P[12] and G14P[12] ERVA genotypes	296:334	G3P[12	300:305	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	2	1	theme	G14P[12	312:318	arg1	genotypes					326:334	The G3P[12] and G14P[12] ERVA genotypes	296:334	genotypes	326:334	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	1	2	theme	health	238:243	arg1	problem					245:251	a major health problem	230:251	a major health problem to the equine breeding industry worldwide	230:293	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	4	3	theme	strains	631:637	arg1	characterization					606:621	the molecular characterization	592:621	the molecular characterization of ERVA strains circulating in central Kentucky	592:669	Here, we performed the molecular characterization of ERVA strains circulating in central Kentucky using fecal samples collected during the 2017 foaling season.
29864502	6	4	theme	*	1196:1196	arg1	*					1196:1196	VP8*	1193:1196	VP8*	1193:1196	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	4	theme	*	1196:1196	arg1	sites					1184:1188	antigenic sites	1174:1188	antigenic sites of VP8*	1174:1196	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	3	5	theme	ERVA	506:509	arg1	strain					519:524	a prototype ERVA G3P[12] strain	494:524	a prototype ERVA G3P[12] strain with limited and controversial field efficacy	494:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	7	6	theme	G14	1325:1327	arg1	strains					1329:1335	other G14 strains	1319:1335	other G14 strains	1319:1335	Also, we report the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world.
29864502	6	7	theme	glycosylation	1109:1121	arg1	site					1123:1126	a non-conserved N-linked glycosylation site	1084:1126	a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1084:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	7	theme	glycosylation	1109:1121	arg1	D123N					1129:1133	D123N	1129:1133	D123N	1129:1133	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	4	8	theme	molecular	596:604	arg1	characterization					606:621	the molecular characterization	592:621	the molecular characterization of ERVA strains circulating in central Kentucky	592:669	Here, we performed the molecular characterization of ERVA strains circulating in central Kentucky using fecal samples collected during the 2017 foaling season.
29864502	5	9	dep	study	865:869	arg1	contrast					831:838	contrast	831:838	contrast	831:838	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	1	10	theme	leading	182:188	arg1	cause					190:194	the leading cause	178:194	the leading cause of diarrhea in neonatal foals	178:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	10	theme	leading	182:188	arg1	A					166:166	Equine rotavirus A	149:166	Equine rotavirus A (ERVA)	149:173	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	7	11	theme	high	1300:1303	arg1	identity					1305:1312	a high identity	1298:1312	a high identity with other G14 strains	1298:1335	Also, we report the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world.
29864502	1	12	from	cause	190:194	arg1	foals					220:224	neonatal foals	211:224	neonatal foals	211:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	13	from	foals	220:224	arg1	problem					245:251	a major health problem	230:251	a major health problem to the equine breeding industry worldwide	230:293	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	13	from	foals	220:224	arg1	cause					190:194	the leading cause	178:194	the leading cause of diarrhea in neonatal foals	178:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	13	from	foals	220:224	arg1	A					166:166	Equine rotavirus A	149:166	Equine rotavirus A (ERVA)	149:173	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	3	14	theme	field	557:561	arg1	efficacy					563:570	limited and controversial field efficacy	531:570	limited and controversial field efficacy	531:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	5	15	theme	only	877:880	arg1	strains					894:900	only G3 genotype strains	877:900	only G3 genotype strains	877:900	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	8	16	theme	ideal	1381:1385	arg1	strains					1397:1403	ideal reference strains	1381:1403	ideal reference strains	1381:1403	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	7	17	theme	strains	1274:1280	arg1	isolation					1241:1249	the successful isolation	1226:1249	the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world	1226:1357	Also, we report the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world.
29864502	6	18	from	changes	1163:1169	arg1	*					1196:1196	VP8*	1193:1196	VP8*	1193:1196	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	18	from	changes	1163:1169	arg1	sites					1184:1188	antigenic sites	1174:1188	antigenic sites of VP8*	1174:1196	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	5	19	theme	genotype	885:892	arg1	strains					894:900	only G3 genotype strains	877:900	only G3 genotype strains	877:900	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	0	20	theme	G3P[12	67:72	arg1	Detection					0:8	Detection	0:8	Detection	0:8	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	0	20	theme	G3P[12	67:72	arg1	characterization					21:36	molecular characterization	11:36	molecular characterization	11:36	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	0	20	theme	G3P[12	67:72	arg1	analysis					55:62	phylogenetic analysis	42:62	phylogenetic analysis	42:62	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	5	21	from	region	821:826	arg1	predominant					801:811	predominant	801:811	predominant	801:811	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	5	21	from	region	821:826	arg1	genotype					789:796	the G14P[12] genotype	776:796	the G14P[12] genotype	776:796	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	1	22	theme	Equine	149:154	arg1	cause					190:194	the leading cause	178:194	the leading cause of diarrhea in neonatal foals	178:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	22	theme	Equine	149:154	arg1	ERVA					169:172	ERVA	169:172	ERVA	169:172	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	22	theme	Equine	149:154	arg1	A					166:166	Equine rotavirus A	149:166	Equine rotavirus A (ERVA)	149:173	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	6	23	theme	VP7	961:963	arg1	protein					965:971	the VP7 protein	957:971	the VP7 protein	957:971	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	24	from	protein	965:971	arg1	analysis					926:933	analysis	926:933	analysis of antigenic sites in the VP7 protein	926:971	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	4	25	theme	fecal	677:681	arg1	samples					683:689	fecal samples	677:689	fecal samples collected during the 2017 foaling season	677:730	Here, we performed the molecular characterization of ERVA strains circulating in central Kentucky using fecal samples collected during the 2017 foaling season.
29864502	3	26	contain	containing	483:492	arg1	vaccine					475:481	an inactivated vaccine	460:481	an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy	460:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	3	26	contain	containing	483:492	arg2	strain					519:524	a prototype ERVA G3P[12] strain	494:524	a prototype ERVA G3P[12] strain with limited and controversial field efficacy	494:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	6	27	theme	antigenic	938:946	arg1	sites					948:952	antigenic sites	938:952	antigenic sites in the VP7 protein	938:971	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	28	from	sites	948:952	arg1	protein					965:971	the VP7 protein	957:971	the VP7 protein	957:971	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	7	29	theme	successful	1230:1239	arg1	isolation					1241:1249	the successful isolation	1226:1249	the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world	1226:1357	Also, we report the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world.
29864502	0	30	theme	rotavirus	95:103	arg1	Detection					0:8	Detection	0:8	Detection	0:8	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	0	30	theme	rotavirus	95:103	arg1	characterization					21:36	molecular characterization	11:36	molecular characterization	11:36	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	0	30	theme	rotavirus	95:103	arg1	analysis					55:62	phylogenetic analysis	42:62	phylogenetic analysis	42:62	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	7	31	theme	ERVA	1260:1263	arg1	strains					1274:1280	three ERVA G14P[12] strains	1254:1280	three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world	1254:1357	Also, we report the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world.
29864502	8	32	theme	G3	1453:1454	arg1	strains					1464:1470	G3 and G14 strains	1453:1470	G3 and G14 strains	1453:1470	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	4	33	theme	foaling	717:723	arg1	season					725:730	the 2017 foaling season	708:730	the 2017 foaling season	708:730	Here, we performed the molecular characterization of ERVA strains circulating in central Kentucky using fecal samples collected during the 2017 foaling season.
29864502	5	34	theme	G14P[12	780:786	arg1	predominant					801:811	predominant	801:811	predominant	801:811	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	5	34	theme	G14P[12	780:786	arg1	genotype					789:796	the G14P[12] genotype	776:796	the G14P[12] genotype	776:796	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	6	35	theme	acid	1016:1019	arg1	substitutions					1021:1033	several amino acid substitutions	1002:1033	several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1002:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	8	36	theme	G14	1460:1462	arg1	strains					1464:1470	G3 and G14 strains	1453:1470	G3 and G14 strains	1453:1470	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	0	37	theme	molecular	11:19	arg1	characterization					21:36	molecular characterization	11:36	molecular characterization	11:36	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	6	38	theme	several	1002:1008	arg1	substitutions					1021:1033	several amino acid substitutions	1002:1033	several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1002:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	39	from	site	1123:1126	arg1	strains					1148:1154	G14P[12] strains	1139:1154	G14P[12] strains	1139:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	5	40	theme	first	760:764	arg1	time					766:769	the first time	756:769	the first time	756:769	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	1	41	theme	breeding	267:274	arg1	worldwide					285:293	the equine breeding industry worldwide	256:293	the equine breeding industry worldwide	256:293	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	8	42	theme	vaccine	1484:1490	arg1	studies					1501:1507	vaccine efficacy studies	1484:1507	vaccine efficacy studies	1484:1507	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	5	43	attach	predominant	801:811	arg2	genotype					789:796	the G14P[12] genotype	776:796	the G14P[12] genotype	776:796	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	5	43	attach	predominant	801:811	arg2	predominant					801:811	predominant	801:811	predominant	801:811	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	5	43	attach	predominant	801:811	arg1	region					821:826	this region	816:826	this region	816:826	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	2	44	from	prevalent	349:357	arg1	foals					362:366	foals	362:366	foals with diarrhea	362:380	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	3	45	theme	pregnant	440:447	arg1	mares					449:453	pregnant mares	440:453	pregnant mares	440:453	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	1	46	theme	diarrhea	199:206	arg1	problem					245:251	a major health problem	230:251	a major health problem to the equine breeding industry worldwide	230:293	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	46	theme	diarrhea	199:206	arg1	cause					190:194	the leading cause	178:194	the leading cause of diarrhea in neonatal foals	178:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	46	theme	diarrhea	199:206	arg1	A					166:166	Equine rotavirus A	149:166	Equine rotavirus A (ERVA)	149:173	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	2	47	from	foals	362:366	arg1	prevalent					349:357	prevalent	349:357	prevalent	349:357	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	2	47	from	foals	362:366	arg1	G3P[12					300:305	The G3P[12] and G14P[12] ERVA genotypes	296:334	G3P[12	300:305	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	2	47	from	foals	362:366	arg1	genotypes					326:334	The G3P[12] and G14P[12] ERVA genotypes	296:334	genotypes	326:334	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	5	48	theme	previous	845:852	arg1	study					865:869	a previous serotyping study	843:869	a previous serotyping study where only G3 genotype strains were reported	843:914	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	8	49	theme	heterologous	1519:1530	arg1	challenge					1532:1540	heterologous challenge	1519:1540	heterologous challenge in the future	1519:1554	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	6	50	from	epitopes	1042:1049	arg1	presence					990:997	the presence	986:997	the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	986:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	1	51	theme	neonatal	211:218	arg1	foals					220:224	neonatal foals	211:224	neonatal foals	211:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	0	52	from	co-circulating	113:126	arg1	Kentucky					139:146	Kentucky	139:146	Kentucky	139:146	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	3	53	theme	inactivated	463:473	arg1	vaccine					475:481	an inactivated vaccine	460:481	an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy	460:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	1	54	from	problem	245:251	arg1	foals					220:224	neonatal foals	211:224	neonatal foals	211:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	3	55	theme	G3P[12	511:516	arg1	strain					519:524	a prototype ERVA G3P[12] strain	494:524	a prototype ERVA G3P[12] strain with limited and controversial field efficacy	494:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	1	56	theme	major	232:236	arg1	problem					245:251	a major health problem	230:251	a major health problem to the equine breeding industry worldwide	230:293	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	2	57	with	foals	362:366	arg1	diarrhea					373:380	diarrhea	373:380	diarrhea	373:380	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	5	58	theme	serotyping	854:863	arg1	study					865:869	a previous serotyping study	843:869	a previous serotyping study where only G3 genotype strains were reported	843:914	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	3	59	theme	prototype	496:504	arg1	strain					519:524	a prototype ERVA G3P[12] strain	494:524	a prototype ERVA G3P[12] strain with limited and controversial field efficacy	494:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	4	60	theme	ERVA	626:629	arg1	strains					631:637	ERVA strains	626:637	ERVA strains circulating in central Kentucky	626:669	Here, we performed the molecular characterization of ERVA strains circulating in central Kentucky using fecal samples collected during the 2017 foaling season.
29864502	6	61	theme	VP8	1193:1195	arg1	*					1196:1196	VP8*	1193:1196	VP8*	1193:1196	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	62	from	presence	990:997	arg1	epitopes					1042:1049	the epitopes	1038:1049	the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1038:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	3	63	theme	limited	531:537	arg1	efficacy					563:570	limited and controversial field efficacy	531:570	limited and controversial field efficacy	531:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	6	64	theme	N-linked	1100:1107	arg1	site					1123:1126	a non-conserved N-linked glycosylation site	1084:1126	a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1084:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	64	theme	N-linked	1100:1107	arg1	D123N					1129:1133	D123N	1129:1133	D123N	1129:1133	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	3	65	with	vaccination	425:435	arg1	vaccine					475:481	an inactivated vaccine	460:481	an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy	460:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	6	66	theme	antigenic	1174:1182	arg1	*					1196:1196	VP8*	1193:1196	VP8*	1193:1196	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	66	theme	antigenic	1174:1182	arg1	sites					1184:1188	antigenic sites	1174:1188	antigenic sites of VP8*	1174:1196	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	3	67	theme	controversial	543:555	arg1	efficacy					563:570	limited and controversial field efficacy	531:570	limited and controversial field efficacy	531:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	8	68	theme	reference	1387:1395	arg1	strains					1397:1403	ideal reference strains	1381:1403	ideal reference strains	1381:1403	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	1	69	from	diarrhea	199:206	arg1	foals					220:224	neonatal foals	211:224	neonatal foals	211:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	5	70	from	predominant	801:811	arg1	region					821:826	this region	816:826	this region	816:826	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	5	71	theme	G3	882:883	arg1	strains					894:900	only G3 genotype strains	877:900	only G3 genotype strains	877:900	The data indicated for the first time that the G14P[12] genotype is predominant in this region in contrast to a previous serotyping study where only G3 genotype strains were reported.
29864502	6	72	gly	glycosylation	1109:1121	arg2	D123N					1129:1133	D123N	1129:1133	D123N	1129:1133	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	72	gly	glycosylation	1109:1121	arg2	site					1123:1126	a non-conserved N-linked glycosylation site	1084:1126	a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1084:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	1	73	theme	rotavirus	156:164	arg1	cause					190:194	the leading cause	178:194	the leading cause of diarrhea in neonatal foals	178:224	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	73	theme	rotavirus	156:164	arg1	ERVA					169:172	ERVA	169:172	ERVA	169:172	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	1	73	theme	rotavirus	156:164	arg1	A					166:166	Equine rotavirus A	149:166	Equine rotavirus A (ERVA)	149:173	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	8	74	theme	molecular	1432:1440	arg1	biology					1442:1448	the molecular biology	1428:1448	the molecular biology of G3 and G14 strains	1428:1470	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	6	75	link	N-linked	1100:1107	arg1	site					1123:1126	a non-conserved N-linked glycosylation site	1084:1126	a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1084:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	75	link	N-linked	1100:1107	arg1	D123N					1129:1133	D123N	1129:1133	D123N	1129:1133	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	0	76	theme	equine	88:93	arg1	rotavirus					95:103	G3P[12] and G14P[12] equine rotavirus	67:103	rotavirus	95:103	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	7	77	theme	other	1319:1323	arg1	strains					1329:1335	other G14 strains	1319:1335	other G14 strains	1319:1335	Also, we report the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world.
29864502	6	78	theme	sites	948:952	arg1	analysis					926:933	analysis	926:933	analysis of antigenic sites in the VP7 protein	926:971	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	3	79	theme	prevention	395:404	arg1	strategies					406:415	Control and prevention strategies	383:415	strategies	406:415	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	3	80	with	strain	519:524	arg1	efficacy					563:570	limited and controversial field efficacy	531:570	limited and controversial field efficacy	531:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	6	81	theme	substitutions	1021:1033	arg1	presence					990:997	the presence	986:997	the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	986:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	8	82	from	challenge	1532:1540	arg1	future					1549:1554	future	1549:1554	future	1549:1554	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	8	83	theme	strains	1464:1470	arg1	biology					1442:1448	the molecular biology	1428:1448	the molecular biology of G3 and G14 strains	1428:1470	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	4	84	theme	2017	712:715	arg1	season					725:730	the 2017 foaling season	708:730	the 2017 foaling season	708:730	Here, we performed the molecular characterization of ERVA strains circulating in central Kentucky using fecal samples collected during the 2017 foaling season.
29864502	3	85	theme	Control	383:389	arg1	strategies					406:415	Control and prevention strategies	383:415	strategies	406:415	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	6	86	theme	amino	1010:1014	arg1	substitutions					1021:1033	several amino acid substitutions	1002:1033	several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1002:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	0	87	theme	phylogenetic	42:53	arg1	analysis					55:62	phylogenetic analysis	42:62	phylogenetic analysis	42:62	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	1	88	theme	equine	260:265	arg1	worldwide					285:293	the equine breeding industry worldwide	256:293	the equine breeding industry worldwide	256:293	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	8	89	theme	efficacy	1492:1499	arg1	studies					1501:1507	vaccine efficacy studies	1484:1507	vaccine efficacy studies	1484:1507	These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future.
29864502	6	90	from	analysis	926:933	arg1	protein					965:971	the VP7 protein	957:971	the VP7 protein	957:971	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	7	91	with	identity	1305:1312	arg1	strains					1329:1335	other G14 strains	1319:1335	other G14 strains	1319:1335	Also, we report the successful isolation of three ERVA G14P[12] strains which presented a high identity with other G14 strains from around the world.
29864502	1	92	theme	industry	276:283	arg1	worldwide					285:293	the equine breeding industry worldwide	256:293	the equine breeding industry worldwide	256:293	Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and a major health problem to the equine breeding industry worldwide.
29864502	6	93	theme	non-conserved	1086:1098	arg1	site					1123:1126	a non-conserved N-linked glycosylation site	1084:1126	a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains	1084:1154	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	6	93	theme	non-conserved	1086:1098	arg1	D123N					1129:1133	D123N	1129:1133	D123N	1129:1133	Overall, analysis of antigenic sites in the VP7 protein demonstrated the presence of several amino acid substitutions in the epitopes exposed on the surface including a non-conserved N-linked glycosylation site (D123N) in G14P[12] strains, while changes in antigenic sites of VP8* were minor.
29864502	0	94	from	Kentucky	139:146	arg1	co-circulating					113:126	co-circulating	113:126	co-circulating	113:126	Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky.
29864502	3	95	theme	mares	449:453	arg1	vaccination					425:435	vaccination	425:435	vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy	425:570	Control and prevention strategies include vaccination of pregnant mares with an inactivated vaccine containing a prototype ERVA G3P[12] strain with limited and controversial field efficacy.
29864502	2	96	theme	ERVA	321:324	arg1	prevalent					349:357	prevalent	349:357	prevalent	349:357	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	2	96	theme	ERVA	321:324	arg1	G3P[12					300:305	The G3P[12] and G14P[12] ERVA genotypes	296:334	G3P[12	300:305	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29864502	2	96	theme	ERVA	321:324	arg1	genotypes					326:334	The G3P[12] and G14P[12] ERVA genotypes	296:334	genotypes	326:334	The G3P[12] and G14P[12] ERVA genotypes are the most prevalent in foals with diarrhea.
29337188	9	0	theme	Fam20c	1675:1680	arg1	cells					1711:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	4	1	theme	primary	580:586	arg1	effects					588:594	the primary effects	576:594	the primary effects of Fam20c on dental mesenchymal cells	576:632	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	9	2	theme	dental	1692:1697	arg1	cells					1711:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	6	3	theme	SIBLING	1177:1183	arg1	ligand					1146:1151	the small integrin-binding ligand	1119:1151	the small integrin-binding ligand	1119:1151	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	3	theme	SIBLING	1177:1183	arg1	family					1186:1191	N-linked glycoprotein (SIBLING) family	1154:1191	N-linked glycoprotein (SIBLING) family	1154:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	8	4	theme	proteins	1380:1387	arg1	supplements					1345:1355	supplements	1345:1355	supplements of the non-collagenous proteins from wild type rat dentin	1345:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	3	5	theme	cell-autonomous	540:554	arg1	manner					556:561	a cell-autonomous manner	538:561	a cell-autonomous manner	538:561	Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner.
29337188	6	6	theme	glycoprotein	1163:1174	arg1	ligand					1146:1151	the small integrin-binding ligand	1119:1151	the small integrin-binding ligand	1119:1151	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	6	theme	glycoprotein	1163:1174	arg1	family					1186:1191	N-linked glycoprotein (SIBLING) family	1154:1191	N-linked glycoprotein (SIBLING) family	1154:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	4	7	theme	mesenchymal	665:675	arg1	cells					677:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	2	8	theme	fibroblast	268:277	arg1	factor					286:291	the elevated fibroblast growth factor 23 (FGF23)	255:302	the elevated fibroblast growth factor 23 (FGF23)	255:302	Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney.
29337188	9	9	theme	kinase	1735:1740	arg1	activity					1742:1749	the kinase activity	1731:1749	the kinase activity of FAM20C	1731:1759	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	6	10	theme	integrin-binding	1129:1144	arg1	ligand					1146:1151	the small integrin-binding ligand	1119:1151	the small integrin-binding ligand	1119:1151	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	10	theme	integrin-binding	1129:1144	arg1	family					1186:1191	N-linked glycoprotein (SIBLING) family	1154:1191	N-linked glycoprotein (SIBLING) family	1154:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	8	11	theme	non-collagenous	1364:1378	arg1	proteins					1380:1387	the non-collagenous proteins	1360:1387	the non-collagenous proteins from wild type rat dentin	1360:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	4	12	with	cells	786:790	arg1	lentivirus					812:821	Cre-expressing lentivirus	797:821	Cre-expressing lentivirus	797:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	4	13	theme	Fam20c-deficient	641:656	arg1	cells					677:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	6	14	theme	Fgf23	1208:1212	arg1	expression					1214:1223	Fgf23 expression	1208:1223	Fgf23 expression	1208:1223	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	15	gly	glycoprotein	1163:1174	arg1	glycoprotein					1163:1174	N-linked glycoprotein (SIBLING) family	1154:1191	N-linked glycoprotein (SIBLING) family	1154:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	5	16	from	impact	857:862	arg1	morphology					872:881	cell morphology	867:881	cell morphology	867:881	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	5	17	theme	dental	937:942	arg1	cells					956:960	the dental mesenchymal cells	933:960	the dental mesenchymal cells	933:960	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	4	18	theme	dental	767:772	arg1	cells					786:790	the immortalized mouse Fam20cf/f dental mesenchymal cells	734:790	the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus	734:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	10	19	theme	cell	1867:1870	arg1	behaviors					1872:1880	cell behaviors	1867:1880	cell behaviors	1867:1880	In summary, our study discloses that Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell-autonomous manner.
29337188	5	20	theme	cells	956:960	arg1	mobility					921:928	mobility	921:928	mobility	921:928	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	5	20	theme	cells	956:960	arg1	proliferation					903:915	proliferation	903:915	proliferation	903:915	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	6	21	theme	I	1047:1047	arg1	a					1058:1058	type I Collagen a 1	1042:1060	type I Collagen a 1 (Col1a1)	1042:1069	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	21	theme	I	1047:1047	arg1	Col1a1					1063:1068	Col1a1	1063:1068	Col1a1	1063:1068	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	5	22	dep	proliferation	903:915	arg1	the					899:901	the	899:901	the	899:901	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	1	23	theme	skeleton	154:161	arg1	mineralization					136:149	the mineralization	132:149	the mineralization of skeleton and tooth in both human and mouse	132:195	FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse.
29337188	0	24	theme	immortalized	65:76	arg1	cells					97:101	immortalized dental mesenchymal cells	65:101	immortalized dental mesenchymal cells	65:101	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	1	25	theme	tooth	167:171	arg1	mineralization					136:149	the mineralization	132:149	the mineralization of skeleton and tooth in both human and mouse	132:195	FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse.
29337188	7	26	dep	in	1244:1245	arg1	vitro					1247:1251	vitro	1247:1251	vitro	1247:1251	Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled.
29337188	0	27	theme	mesenchymal	85:95	arg1	cells					97:101	immortalized dental mesenchymal cells	65:101	immortalized dental mesenchymal cells	65:101	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	4	28	from	cells	786:790	arg1	alleles					721:727	the floxed alleles	710:727	the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus	710:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	4	29	theme	Cre-expressing	797:810	arg1	lentivirus					812:821	Cre-expressing lentivirus	797:821	Cre-expressing lentivirus	797:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	3	30	theme	systemic	423:430	arg1	homeostasis					443:453	systemic phosphorus homeostasis	423:453	systemic phosphorus homeostasis	423:453	Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner.
29337188	6	31	theme	Alkaline	1072:1079	arg1	Alpl					1094:1097	Alpl	1094:1097	Alpl	1094:1097	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	31	theme	Alkaline	1072:1079	arg1	phosphatase					1081:1091	Alkaline phosphatase	1072:1091	Alkaline phosphatase (Alpl)	1072:1098	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	4	32	theme	mouse	751:755	arg1	cells					786:790	the immortalized mouse Fam20cf/f dental mesenchymal cells	734:790	the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus	734:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	5	33	theme	Fam20c	839:844	arg1	removal					828:834	The removal	824:834	The removal of Fam20c	824:844	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	8	34	theme	wild	1394:1397	arg1	dentin					1408:1413	wild type rat dentin	1394:1413	wild type rat dentin	1394:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	0	35	theme	Fam20c	14:19	arg1	Abrogation					0:9	Abrogation	0:9	Abrogation of Fam20c	0:19	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	1	36	theme	FAM20C	104:109	arg1	mutations					111:119	FAM20C mutations	104:119	FAM20C mutations	104:119	FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse.
29337188	10	37	theme	signaling	1891:1899	arg1	pathway					1901:1907	cell signaling pathway	1886:1907	cell signaling pathway	1886:1907	In summary, our study discloses that Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell-autonomous manner.
29337188	8	38	theme	rat	1404:1406	arg1	dentin					1408:1413	wild type rat dentin	1394:1413	wild type rat dentin	1394:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	0	39	theme	cell	29:32	arg1	behaviors					34:42	cell behaviors	29:42	cell behaviors	29:42	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	7	40	theme	mesenchymal	1295:1305	arg1	cells					1307:1311	Fam20c-deficient dental mesenchymal cells	1271:1311	Fam20c-deficient dental mesenchymal cells	1271:1311	Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled.
29337188	8	41	theme	phosphorus	1593:1602	arg1	metabolism					1604:1613	systemic phosphorus metabolism	1584:1613	systemic phosphorus metabolism	1584:1613	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	2	42	theme	serum	323:327	arg1	phosphorus					329:338	the serum phosphorus	319:338	the serum phosphorus	319:338	Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney.
29337188	9	43	theme	BMP	1645:1647	arg1	pathways					1659:1666	the down-regulated BMP signaling pathways	1626:1666	the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells	1626:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	7	44	theme	Fam20c-deficient	1271:1286	arg1	cells					1307:1311	Fam20c-deficient dental mesenchymal cells	1271:1311	Fam20c-deficient dental mesenchymal cells	1271:1311	Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled.
29337188	10	45	theme	cell-autonomous	1914:1928	arg1	manner					1930:1935	a cell-autonomous manner	1912:1935	a cell-autonomous manner	1912:1935	In summary, our study discloses that Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell-autonomous manner.
29337188	4	46	theme	Fam20c	599:604	arg1	effects					588:594	the primary effects	576:594	the primary effects of Fam20c on dental mesenchymal cells	576:632	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	6	47	theme	a	1058:1058	arg1	expression					1012:1021	the expression	1008:1021	the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family	1008:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	8	48	theme	compromised	1436:1446	arg1	mineralization					1448:1461	the compromised mineralization	1432:1461	the compromised mineralization	1432:1461	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	7	49	theme	in	1244:1245	arg1	mineralization					1253:1266	the in vitro mineralization	1240:1266	the in vitro mineralization of Fam20c-deficient dental mesenchymal cells	1240:1311	Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled.
29337188	4	50	theme	dental	609:614	arg1	cells					628:632	dental mesenchymal cells	609:632	dental mesenchymal cells	609:632	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	3	51	theme	cell	495:498	arg1	behaviors					500:508	cell behaviors	495:508	cell behaviors	495:508	Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner.
29337188	9	52	theme	deficient	1682:1690	arg1	cells					1711:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	9	53	theme	mesenchymal	1699:1709	arg1	cells					1711:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	2	54	theme	growth	279:284	arg1	factor					286:291	the elevated fibroblast growth factor 23 (FGF23)	255:302	the elevated fibroblast growth factor 23 (FGF23)	255:302	Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney.
29337188	8	55	from	dentin	1408:1413	arg1	proteins					1380:1387	the non-collagenous proteins	1360:1387	the non-collagenous proteins from wild type rat dentin	1360:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	8	55	from	dentin	1408:1413	arg1	supplements					1345:1355	supplements	1345:1355	supplements of the non-collagenous proteins from wild type rat dentin	1345:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	6	56	theme	N-linked	1154:1161	arg1	ligand					1146:1151	the small integrin-binding ligand	1119:1151	the small integrin-binding ligand	1119:1151	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	56	theme	N-linked	1154:1161	arg1	family					1186:1191	N-linked glycoprotein (SIBLING) family	1154:1191	N-linked glycoprotein (SIBLING) family	1154:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	4	57	theme	dental	658:663	arg1	cells					677:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	6	58	theme	ligand	1146:1151	arg1	members					1108:1114	the members	1104:1114	the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family	1104:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	58	theme	ligand	1146:1151	arg1	a					1058:1058	type I Collagen a 1	1042:1060	type I Collagen a 1 (Col1a1)	1042:1069	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	58	theme	ligand	1146:1151	arg1	Runx2					1035:1039	Runx2	1035:1039	Runx2	1035:1039	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	58	theme	ligand	1146:1151	arg1	Col1a1					1063:1068	Col1a1	1063:1068	Col1a1	1063:1068	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	58	theme	ligand	1146:1151	arg1	Alpl					1094:1097	Alpl	1094:1097	Alpl	1094:1097	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	58	theme	ligand	1146:1151	arg1	Osterix					1026:1032	Osterix	1026:1032	Osterix	1026:1032	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	58	theme	ligand	1146:1151	arg1	phosphatase					1081:1091	Alkaline phosphatase	1072:1091	Alkaline phosphatase (Alpl)	1072:1098	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	59	theme	small	1123:1127	arg1	ligand					1146:1151	the small integrin-binding ligand	1119:1151	the small integrin-binding ligand	1119:1151	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	59	theme	small	1123:1127	arg1	family					1186:1191	N-linked glycoprotein (SIBLING) family	1154:1191	N-linked glycoprotein (SIBLING) family	1154:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	5	60	theme	cell	867:870	arg1	morphology					872:881	cell morphology	867:881	cell morphology	867:881	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	9	61	theme	FAM20C	1754:1759	arg1	activity					1742:1749	the kinase activity	1731:1749	the kinase activity of FAM20C	1731:1759	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	4	62	theme	mouse	635:639	arg1	cells					677:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	mouse Fam20c-deficient dental mesenchymal cells	635:681	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	2	63	theme	mineralization	214:227	arg1	disorder					229:236	the mineralization disorder	210:236	the mineralization disorder	210:236	Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney.
29337188	6	64	theme	Fam20c	963:968	arg1	deficiency					970:979	Fam20c deficiency	963:979	Fam20c deficiency	963:979	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	4	65	theme	floxed	714:719	arg1	alleles					721:727	the floxed alleles	710:727	the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus	710:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	2	66	theme	elevated	259:266	arg1	factor					286:291	the elevated fibroblast growth factor 23 (FGF23)	255:302	the elevated fibroblast growth factor 23 (FGF23)	255:302	Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney.
29337188	5	67	theme	mesenchymal	944:954	arg1	cells					956:960	the dental mesenchymal cells	933:960	the dental mesenchymal cells	933:960	The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells.
29337188	6	68	theme	Collagen	1049:1056	arg1	a					1058:1058	type I Collagen a 1	1042:1060	type I Collagen a 1 (Col1a1)	1042:1069	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	68	theme	Collagen	1049:1056	arg1	Col1a1					1063:1068	Col1a1	1063:1068	Col1a1	1063:1068	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	8	69	theme	FAM20C	1493:1498	arg1	roles					1484:1488	the roles	1480:1488	the roles of FAM20C in tooth mineralization	1480:1522	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	8	69	theme	FAM20C	1493:1498	arg1	phosphorylating					1538:1552	phosphorylating	1538:1552	phosphorylating local matrices	1538:1567	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	6	70	link	N-linked	1154:1161	arg1	ligand					1146:1151	the small integrin-binding ligand	1119:1151	the small integrin-binding ligand	1119:1151	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	70	link	N-linked	1154:1161	arg1	family					1186:1191	N-linked glycoprotein (SIBLING) family	1154:1191	N-linked glycoprotein (SIBLING) family	1154:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	71	theme	type	1042:1045	arg1	a					1058:1058	type I Collagen a 1	1042:1060	type I Collagen a 1 (Col1a1)	1042:1069	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	6	71	theme	type	1042:1045	arg1	Col1a1					1063:1068	Col1a1	1063:1068	Col1a1	1063:1068	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	9	72	theme	BMP	1791:1793	arg1	signaling					1795:1803	BMP signaling	1791:1803	BMP signaling	1791:1803	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	8	73	theme	tooth	1503:1507	arg1	mineralization					1509:1522	tooth mineralization	1503:1522	tooth mineralization	1503:1522	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	4	74	from	effects	588:594	arg1	cells					628:632	dental mesenchymal cells	609:632	dental mesenchymal cells	609:632	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	0	75	theme	dental	78:83	arg1	cells					97:101	immortalized dental mesenchymal cells	65:101	immortalized dental mesenchymal cells	65:101	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	6	76	theme	Runx2	1035:1039	arg1	expression					1012:1021	the expression	1008:1021	the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family	1008:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	0	77	theme	cells	97:101	arg1	behaviors					34:42	cell behaviors	29:42	cell behaviors	29:42	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	0	77	theme	cells	97:101	arg1	signaling					52:60	BMP signaling	48:60	BMP signaling	48:60	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	6	78	theme	Osterix	1026:1032	arg1	expression					1012:1021	the expression	1008:1021	the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family	1008:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	4	79	theme	mesenchymal	774:784	arg1	cells					786:790	the immortalized mouse Fam20cf/f dental mesenchymal cells	734:790	the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus	734:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	8	80	from	roles	1484:1488	arg1	mineralization					1509:1522	tooth mineralization	1503:1522	tooth mineralization	1503:1522	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	6	81	theme	phosphatase	1081:1091	arg1	expression					1012:1021	the expression	1008:1021	the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family	1008:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	8	82	theme	local	1554:1558	arg1	matrices					1560:1567	local matrices	1554:1567	local matrices	1554:1567	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	2	83	theme	phosphorus	375:384	arg1	reabsorption					359:370	the reabsorption	355:370	the reabsorption of phosphorus in kidney	355:394	Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney.
29337188	1	84	from	mineralization	136:149	arg1	human					181:185	human	181:185	human	181:185	FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse.
29337188	1	84	from	mineralization	136:149	arg1	mouse					191:195	mouse	191:195	mouse	191:195	FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse.
29337188	9	85	from	pathways	1659:1666	arg1	cells					1711:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	the Fam20c deficient dental mesenchymal cells	1671:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	4	86	theme	immortalized	738:749	arg1	cells					786:790	the immortalized mouse Fam20cf/f dental mesenchymal cells	734:790	the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus	734:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	7	87	theme	cells	1307:1311	arg1	mineralization					1253:1266	the in vitro mineralization	1240:1266	the in vitro mineralization of Fam20c-deficient dental mesenchymal cells	1240:1311	Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled.
29337188	8	88	theme	systemic	1584:1591	arg1	metabolism					1604:1613	systemic phosphorus metabolism	1584:1613	systemic phosphorus metabolism	1584:1613	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	4	89	theme	Fam20cf/f	757:765	arg1	cells					786:790	the immortalized mouse Fam20cf/f dental mesenchymal cells	734:790	the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus	734:821	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	7	90	theme	dental	1288:1293	arg1	cells					1307:1311	Fam20c-deficient dental mesenchymal cells	1271:1311	Fam20c-deficient dental mesenchymal cells	1271:1311	Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled.
29337188	10	91	theme	cell	1886:1889	arg1	pathway					1901:1907	cell signaling pathway	1886:1907	cell signaling pathway	1886:1907	In summary, our study discloses that Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell-autonomous manner.
29337188	8	92	theme	type	1399:1402	arg1	dentin					1408:1413	wild type rat dentin	1394:1413	wild type rat dentin	1394:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	0	93	theme	BMP	48:50	arg1	signaling					52:60	BMP signaling	48:60	BMP signaling	48:60	Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells.
29337188	9	94	theme	down-regulated	1630:1643	arg1	pathways					1659:1666	the down-regulated BMP signaling pathways	1626:1666	the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells	1626:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	2	95	from	reabsorption	359:370	arg1	kidney					389:394	kidney	389:394	kidney	389:394	Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney.
29337188	9	96	theme	signaling	1649:1657	arg1	pathways					1659:1666	the down-regulated BMP signaling pathways	1626:1666	the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells	1626:1715	Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling.
29337188	6	97	theme	members	1108:1114	arg1	expression					1012:1021	the expression	1008:1021	the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family	1008:1191	Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression.
29337188	3	98	from	regulation	409:418	arg1	homeostasis					443:453	systemic phosphorus homeostasis	423:453	systemic phosphorus homeostasis	423:453	Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner.
29337188	8	99	from	supplements	1345:1355	arg1	dentin					1408:1413	wild type rat dentin	1394:1413	wild type rat dentin	1394:1413	However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism.
29337188	3	100	theme	phosphorus	432:441	arg1	homeostasis					443:453	systemic phosphorus homeostasis	423:453	systemic phosphorus homeostasis	423:453	Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner.
29337188	4	101	theme	mesenchymal	616:626	arg1	cells					628:632	dental mesenchymal cells	609:632	dental mesenchymal cells	609:632	To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing lentivirus.
29337188	3	102	theme	gene	514:517	arg1	expression					519:528	gene expression	514:528	gene expression	514:528	Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner.
28031460	7	0	theme	3T3-L1	1218:1223	arg1	cells					1225:1229	differentiating 3T3-L1 cells	1202:1229	differentiating 3T3-L1 cells	1202:1229	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	6	1	from	proteins	1033:1040	arg1	tissues					1053:1059	adipose tissues	1045:1059	adipose tissues	1045:1059	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	10	2	theme	regulation	1753:1762	arg1	mechanisms					1764:1773	regulation mechanisms	1753:1773	regulation mechanisms	1753:1773	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	3	3	theme	high-fat	560:567	arg1	HFD					575:577	HFD	575:577	HFD	575:577	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	3	theme	high-fat	560:567	arg1	diet					569:572	high-fat diet	560:572	high-fat diet (HFD)	560:578	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	1	4	theme	related	108:114	arg1	diseases					116:123	related diseases	108:123	related diseases such as diabetes and cardiovascular diseases	108:168	Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases.
28031460	1	4	theme	related	108:114	arg1	diabetes					133:140	diabetes	133:140	diabetes	133:140	Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases.
28031460	1	4	theme	related	108:114	arg1	diseases					161:168	cardiovascular diseases	146:168	cardiovascular diseases	146:168	Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases.
28031460	9	5	from	involvement	1542:1552	arg1	silencing					1595:1603	St6gal1 silencing	1587:1603	St6gal1 silencing	1587:1603	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	2	6	theme	obesity-related	275:289	arg1	diseases					291:298	obesity-related diseases	275:298	obesity-related diseases	275:298	Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear.
28031460	10	7	from	role	1658:1661	arg1	adipogenesis					1666:1677	adipogenesis	1666:1677	adipogenesis	1666:1677	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	4	8	theme	β-galactoside	630:642	arg1	St6gal1					670:676	St6gal1	670:676	St6gal1	670:676	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	4	8	theme	β-galactoside	630:642	arg1	α2,6-sialyltransferase-1					644:667	β-galactoside α2,6-sialyltransferase-1	630:667	β-galactoside α2,6-sialyltransferase-1 (St6gal1)	630:677	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	4	8	theme	β-galactoside	630:642	arg1	enzyme					686:691	a key enzyme	680:691	a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans	680:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	6	9	theme	adhesion	1115:1122	arg1	kinase					1124:1129	its downstream molecule focal adhesion kinase	1085:1129	its downstream molecule focal adhesion kinase	1085:1129	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	3	10	theme	control	543:549	arg1	mice					551:554	control mice	543:554	control mice	543:554	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	2	11	theme	posttranslational	226:242	arg1	glycans					201:207	glycans	201:207	glycans	201:207	Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear.
28031460	2	11	theme	posttranslational	226:242	arg1	modifications					244:256	the most common posttranslational modifications	210:256	the most common posttranslational modifications	210:256	Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear.
28031460	9	12	theme	DNA	1495:1497	arg1	inhibitor					1517:1525	a DNA methyltransferase inhibitor	1493:1525	a DNA methyltransferase inhibitor	1493:1525	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	7	13	from	overexpression	1184:1197	arg1	cells					1225:1229	differentiating 3T3-L1 cells	1202:1229	differentiating 3T3-L1 cells	1202:1229	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	5	14	theme	obese	883:887	arg1	mice					889:892	obese mice	883:892	obese mice	883:892	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	6	15	theme	HFD	1163:1165	arg1	feeding					1167:1173	HFD feeding	1163:1173	HFD feeding	1163:1173	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	7	16	theme	kinase	1303:1308	arg1	phosphorylation					1269:1283	increased phosphorylation	1259:1283	increased phosphorylation of focal adhesion kinase	1259:1308	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	7	17	theme	differentiating	1202:1216	arg1	cells					1225:1229	differentiating 3T3-L1 cells	1202:1229	differentiating 3T3-L1 cells	1202:1229	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	3	18	theme	-induced	579:586	arg1	mice					594:597	high-fat diet (HFD)-induced obese mice	560:597	high-fat diet (HFD)-induced obese mice	560:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	0	19	from	Role	15:18	arg1	Adipogenesis					43:54	Adipogenesis	43:54	Adipogenesis	43:54	The Inhibitory Role of α2,6-Sialylation in Adipogenesis.
28031460	8	20	theme	knockout	1332:1339	arg1	mice					1341:1344	St6gal1 knockout mice	1324:1344	St6gal1 knockout mice	1324:1344	Furthermore, St6gal1 knockout mice exhibited increased bodyweight and VAT weight after HFD feeding.
28031460	4	21	from	acid	748:751	arg1	glycans					765:771	N-linked glycans	756:771	N-linked glycans	756:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	9	22	theme	epigenetic	1557:1566	arg1	methylation					1572:1582	epigenetic DNA methylation	1557:1582	epigenetic DNA methylation	1557:1582	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	4	23	theme	α2,6-linked	729:739	arg1	acid					748:751	α2,6-linked sialic acid	729:751	α2,6-linked sialic acid in N-linked glycans	729:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	4	24	from	mice	817:820	arg1	VATs					801:804	VATs	801:804	VATs from obese mice	801:820	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	5	25	from	reduction	840:848	arg1	VATs					873:876	VATs	873:876	VATs from obese mice and differentiated adipocyte model 3T3-L1 cells	873:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	5	25	from	reduction	840:848	arg1	mice					889:892	obese mice	883:892	obese mice	883:892	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	5	25	from	reduction	840:848	arg1	acid					865:868	α2,6-sialic acid	853:868	α2,6-sialic acid	853:868	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	5	25	from	reduction	840:848	arg1	cells					936:940	differentiated adipocyte model 3T3-L1 cells	898:940	differentiated adipocyte model 3T3-L1 cells	898:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	9	26	theme	methylation	1572:1582	arg1	involvement					1542:1552	an involvement	1539:1552	an involvement of epigenetic DNA methylation in St6gal1 silencing	1539:1603	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	10	27	theme	new	1721:1723	arg1	insights					1725:1732	new insights	1721:1732	new insights into the roles and regulation mechanisms of glycans in adipocytes	1721:1798	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	4	28	theme	acid	748:751	arg1	biosynthesis					713:724	the biosynthesis	709:724	the biosynthesis of α2,6-linked sialic acid in N-linked glycans	709:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	4	29	from	biosynthesis	713:724	arg1	glycans					765:771	N-linked glycans	756:771	N-linked glycans	756:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	1	30	theme	critical	78:85	arg1	roles					87:91	critical roles	78:91	critical roles	78:91	Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases.
28031460	8	31	theme	VAT	1381:1383	arg1	weight					1385:1390	VAT weight	1381:1390	VAT weight	1381:1390	Furthermore, St6gal1 knockout mice exhibited increased bodyweight and VAT weight after HFD feeding.
28031460	3	32	from	mice	594:597	arg1	VATs					532:535	VATs	532:535	VATs	532:535	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	32	from	mice	594:597	arg1	levels					424:429	the mRNA levels	415:429	the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	415:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	32	from	mice	594:597	arg1	tissues					523:529	visceral adipose tissues	506:529	visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	506:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	6	33	theme	α2,6-sialylated	1017:1031	arg1	proteins					1033:1040	the target α2,6-sialylated proteins	1006:1040	the target α2,6-sialylated proteins in adipose tissues	1006:1059	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	10	34	from	roles	1743:1747	arg1	adipocytes					1789:1798	adipocytes	1789:1798	adipocytes	1789:1798	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	5	35	theme	adipocyte	913:921	arg1	cells					936:940	differentiated adipocyte model 3T3-L1 cells	898:940	differentiated adipocyte model 3T3-L1 cells	898:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	9	36	with	treatment	1478:1486	arg1	inhibitor					1517:1525	a DNA methyltransferase inhibitor	1493:1525	a DNA methyltransferase inhibitor	1493:1525	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	4	37	link	N-linked	756:763	arg1	glycans					765:771	N-linked glycans	756:771	N-linked glycans	756:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	0	38	theme	α2,6-Sialylation	23:38	arg1	Role					15:18	The Inhibitory Role	0:18	The Inhibitory Role of α2,6-Sialylation in Adipogenesis	0:54	The Inhibitory Role of α2,6-Sialylation in Adipogenesis.
28031460	7	39	theme	adhesion	1294:1301	arg1	kinase					1303:1308	focal adhesion kinase	1288:1308	focal adhesion kinase	1288:1308	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	3	40	theme	related	486:492	arg1	enzymes					494:500	23 related enzymes	483:500	23 related enzymes	483:500	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	10	41	contain	has	1640:1642	arg1	ST6GAL1					1632:1638	ST6GAL1	1632:1638	ST6GAL1	1632:1638	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	10	41	contain	has	1640:1642	arg2	role					1658:1661	an inhibitory role	1644:1661	an inhibitory role in adipogenesis	1644:1677	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	6	42	theme	downstream	1089:1098	arg1	kinase					1124:1129	its downstream molecule focal adhesion kinase	1085:1129	its downstream molecule focal adhesion kinase	1085:1129	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	6	43	gly	α2,6-sialylated	1017:1031	arg1	proteins					1033:1040	the target α2,6-sialylated proteins	1006:1040	the target α2,6-sialylated proteins in adipose tissues	1006:1059	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	4	44	theme	N-linked	756:763	arg1	glycans					765:771	N-linked glycans	756:771	N-linked glycans	756:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	7	45	theme	increased	1259:1267	arg1	phosphorylation					1269:1283	increased phosphorylation	1259:1283	increased phosphorylation of focal adhesion kinase	1259:1308	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	10	46	theme	glycans	1778:1784	arg1	roles					1743:1747	the roles	1739:1747	the roles	1739:1747	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	10	46	theme	glycans	1778:1784	arg1	mechanisms					1764:1773	regulation mechanisms	1753:1773	regulation mechanisms	1753:1773	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	9	47	theme	St6gal1	1434:1440	arg1	down-regulation					1415:1429	The down-regulation	1411:1429	The down-regulation of St6gal1 during adipogenesis	1411:1460	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	5	48	theme	α2,6-sialic	853:863	arg1	acid					865:868	α2,6-sialic acid	853:868	α2,6-sialic acid	853:868	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	10	49	from	mechanisms	1764:1773	arg1	adipocytes					1789:1798	adipocytes	1789:1798	adipocytes	1789:1798	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	2	50	theme	glycan	318:323	arg1	type					310:313	type	310:313	type of glycan	310:323	Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear.
28031460	4	51	theme	obese	811:815	arg1	mice					817:820	obese mice	811:820	obese mice	811:820	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	6	52	theme	kinase	1124:1129	arg1	phosphorylation					1066:1080	phosphorylation	1066:1080	phosphorylation of its downstream molecule focal adhesion kinase	1066:1129	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	6	53	theme	focal	1109:1113	arg1	kinase					1124:1129	its downstream molecule focal adhesion kinase	1085:1129	its downstream molecule focal adhesion kinase	1085:1129	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	10	54	theme	inhibitory	1647:1656	arg1	role					1658:1661	an inhibitory role	1644:1661	an inhibitory role in adipogenesis	1644:1677	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	2	55	theme	common	219:224	arg1	glycans					201:207	glycans	201:207	glycans	201:207	Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear.
28031460	2	55	theme	common	219:224	arg1	modifications					244:256	the most common posttranslational modifications	210:256	the most common posttranslational modifications	210:256	Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear.
28031460	9	56	theme	methyltransferase	1499:1515	arg1	inhibitor					1517:1525	a DNA methyltransferase inhibitor	1493:1525	a DNA methyltransferase inhibitor	1493:1525	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	3	57	theme	obese	588:592	arg1	mice					594:597	high-fat diet (HFD)-induced obese mice	560:597	high-fat diet (HFD)-induced obese mice	560:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	5	58	theme	model	923:927	arg1	cells					936:940	differentiated adipocyte model 3T3-L1 cells	898:940	differentiated adipocyte model 3T3-L1 cells	898:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	4	59	theme	key	682:684	arg1	α2,6-sialyltransferase-1					644:667	β-galactoside α2,6-sialyltransferase-1	630:667	β-galactoside α2,6-sialyltransferase-1 (St6gal1)	630:677	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	4	59	theme	key	682:684	arg1	enzyme					686:691	a key enzyme	680:691	a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans	680:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	3	60	from	mice	551:554	arg1	VATs					532:535	VATs	532:535	VATs	532:535	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	60	from	mice	551:554	arg1	levels					424:429	the mRNA levels	415:429	the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	415:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	60	from	mice	551:554	arg1	tissues					523:529	visceral adipose tissues	506:529	visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	506:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	4	61	from	glycans	765:771	arg1	biosynthesis					713:724	the biosynthesis	709:724	the biosynthesis of α2,6-linked sialic acid in N-linked glycans	709:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	7	62	theme	St6gal1	1176:1182	arg1	overexpression					1184:1197	St6gal1 overexpression	1176:1197	St6gal1 overexpression in differentiating 3T3-L1 cells	1176:1229	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	1	63	theme	cardiovascular	146:159	arg1	diseases					161:168	cardiovascular diseases	146:168	cardiovascular diseases	146:168	Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases.
28031460	8	64	theme	St6gal1	1324:1330	arg1	mice					1341:1344	St6gal1 knockout mice	1324:1344	St6gal1 knockout mice	1324:1344	Furthermore, St6gal1 knockout mice exhibited increased bodyweight and VAT weight after HFD feeding.
28031460	1	65	theme	Adipose	57:63	arg1	tissue					65:70	Adipose tissue	57:70	Adipose tissue	57:70	Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases.
28031460	6	66	theme	proteomic	949:957	arg1	analysis					959:966	proteomic analysis	949:966	proteomic analysis	949:966	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	5	67	theme	3T3-L1	929:934	arg1	cells					936:940	differentiated adipocyte model 3T3-L1 cells	898:940	differentiated adipocyte model 3T3-L1 cells	898:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	6	68	theme	adipose	1045:1051	arg1	tissues					1053:1059	adipose tissues	1045:1059	adipose tissues	1045:1059	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	4	69	theme	sialic	741:746	arg1	acid					748:751	α2,6-linked sialic acid	729:751	α2,6-linked sialic acid in N-linked glycans	729:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	10	70	theme	integrin-β1	1687:1697	arg1	activation					1699:1708	integrin-β1 activation	1687:1708	integrin-β1 activation	1687:1708	Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
28031460	0	71	theme	Inhibitory	4:13	arg1	Role					15:18	The Inhibitory Role	0:18	The Inhibitory Role of α2,6-Sialylation in Adipogenesis	0:54	The Inhibitory Role of α2,6-Sialylation in Adipogenesis.
28031460	9	72	theme	St6gal1	1587:1593	arg1	silencing					1595:1603	St6gal1 silencing	1587:1603	St6gal1 silencing	1587:1603	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	6	73	theme	proteins	1033:1040	arg1	proteins					1033:1040	the target α2,6-sialylated proteins	1006:1040	the target α2,6-sialylated proteins in adipose tissues	1006:1059	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	6	73	theme	proteins	1033:1040	arg1	one					999:1001	one	999:1001	one	999:1001	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	6	73	theme	proteins	1033:1040	arg1	integrin-β1					969:979	integrin-β1	969:979	integrin-β1	969:979	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	4	74	theme	responsible	693:703	arg1	α2,6-sialyltransferase-1					644:667	β-galactoside α2,6-sialyltransferase-1	630:667	β-galactoside α2,6-sialyltransferase-1 (St6gal1)	630:677	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	4	74	theme	responsible	693:703	arg1	enzyme					686:691	a key enzyme	680:691	a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans	680:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	5	75	theme	differentiated	898:911	arg1	cells					936:940	differentiated adipocyte model 3T3-L1 cells	898:940	differentiated adipocyte model 3T3-L1 cells	898:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	6	76	theme	target	1010:1015	arg1	proteins					1033:1040	the target α2,6-sialylated proteins	1006:1040	the target α2,6-sialylated proteins in adipose tissues	1006:1059	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	3	77	theme	visceral	506:513	arg1	VATs					532:535	VATs	532:535	VATs	532:535	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	77	theme	visceral	506:513	arg1	tissues					523:529	visceral adipose tissues	506:529	visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	506:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	7	78	theme	focal	1288:1292	arg1	kinase					1303:1308	focal adhesion kinase	1288:1308	focal adhesion kinase	1288:1308	St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase.
28031460	3	79	theme	mRNA	419:422	arg1	levels					424:429	the mRNA levels	415:429	the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	415:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	2	80	theme	Previous	171:178	arg1	reports					180:186	Previous reports	171:186	Previous reports	171:186	Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear.
28031460	8	81	theme	HFD	1398:1400	arg1	feeding					1402:1408	HFD feeding	1398:1408	HFD feeding	1398:1408	Furthermore, St6gal1 knockout mice exhibited increased bodyweight and VAT weight after HFD feeding.
28031460	6	82	theme	molecule	1100:1107	arg1	kinase					1124:1129	its downstream molecule focal adhesion kinase	1085:1129	its downstream molecule focal adhesion kinase	1085:1129	Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.
28031460	9	83	theme	DNA	1568:1570	arg1	methylation					1572:1582	epigenetic DNA methylation	1557:1582	epigenetic DNA methylation	1557:1582	The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing.
28031460	4	84	link	α2,6-linked	729:739	arg1	acid					748:751	α2,6-linked sialic acid	729:751	α2,6-linked sialic acid in N-linked glycans	729:771	We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice.
28031460	8	85	theme	increased	1356:1364	arg1	bodyweight					1366:1375	increased bodyweight	1356:1375	increased bodyweight	1356:1375	Furthermore, St6gal1 knockout mice exhibited increased bodyweight and VAT weight after HFD feeding.
28031460	3	86	from	levels	424:429	arg1	VATs					532:535	VATs	532:535	VATs	532:535	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	86	from	levels	424:429	arg1	tissues					523:529	visceral adipose tissues	506:529	visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	506:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	86	from	levels	424:429	arg1	mice					551:554	control mice	543:554	control mice	543:554	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	86	from	levels	424:429	arg1	mice					594:597	high-fat diet (HFD)-induced obese mice	560:597	high-fat diet (HFD)-induced obese mice	560:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	5	87	from	mice	889:892	arg1	VATs					873:876	VATs	873:876	VATs from obese mice and differentiated adipocyte model 3T3-L1 cells	873:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	5	87	from	mice	889:892	arg1	reduction					840:848	the reduction	836:848	the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells	836:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	3	88	theme	genes	438:442	arg1	levels					424:429	the mRNA levels	415:429	the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	415:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	89	theme	adipose	515:521	arg1	VATs					532:535	VATs	532:535	VATs	532:535	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	3	89	theme	adipose	515:521	arg1	tissues					523:529	visceral adipose tissues	506:529	visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice	506:597	In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice.
28031460	5	90	from	cells	936:940	arg1	VATs					873:876	VATs	873:876	VATs from obese mice and differentiated adipocyte model 3T3-L1 cells	873:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
28031460	5	90	from	cells	936:940	arg1	reduction					840:848	the reduction	836:848	the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells	836:940	We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells.
27704558	10	0	theme	BSP-/-	1778:1783	arg1	mice					1785:1788	BSP-/- mice	1778:1788	BSP-/- mice	1778:1788	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	11	1	theme	higher	2017:2022	arg1	expression					2024:2033	higher expression	2017:2033	higher expression of VEGF	2017:2041	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	8	2	theme	BSP-/-	1366:1371	arg1	stages					1397:1402	BSP-/- and more differentiated stages	1366:1402	BSP-/- and more differentiated stages were more abundant	1366:1421	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	3	3	theme	bone	500:503	arg1	marrow					505:510	bone marrow	500:510	bone marrow ablation	500:519	In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice.
27704558	4	4	theme	BSP-/-	763:768	arg1	mice					770:773	2 month old BSP+/+ and BSP-/- mice	740:773	2 month old BSP+/+ and BSP-/- mice	740:773	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	7	5	theme	stem	1199:1202	arg1	cells					1204:1208	hematopoietic stem cells	1185:1208	hematopoietic stem cells (HSC: Flt3- LSK, ×2)	1185:1229	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	6	theme	Flt3-	1216:1220	arg1	LSK					1222:1224	Flt3- LSK	1216:1224	Flt3- LSK	1216:1224	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	1	7	theme	tissue	190:195	arg1	activity					173:180	the activity	169:180	the activity of bone tissue, bone marrow, and blood vessels	169:227	The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined.
27704558	6	8	theme	vessel	1057:1062	arg1	size					1064:1067	smaller vessel size	1049:1067	smaller vessel size	1049:1067	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	10	9	from	ablation	1766:1773	arg1	mice					1785:1788	BSP-/- mice	1778:1788	BSP-/- mice	1778:1788	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	0	10	theme	Hematopoietic	113:125	arg1	Recolonization					127:140	Faster Hematopoietic Recolonization	106:140	Faster Hematopoietic Recolonization	106:140	Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
27704558	1	11	theme	bone	198:201	arg1	marrow					203:208	bone marrow	198:208	bone marrow	198:208	The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined.
27704558	6	12	theme	ablated	1072:1078	arg1	mutants					1080:1086	ablated mutants	1072:1086	ablated mutants	1072:1086	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	3	13	theme	medullary	550:558	arg1	bone					560:563	medullary bone	550:563	medullary bone	550:563	In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice.
27704558	8	14	theme	hematopoietic	1476:1488	arg1	differentiation					1490:1504	hematopoietic differentiation	1476:1504	hematopoietic differentiation	1476:1504	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	7	15	theme	IL-7Rα-	1151:1157	arg1	×2					1177:1178	×2	1177:1178	×2	1177:1178	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	15	theme	IL-7Rα-	1151:1157	arg1	c-Kithi					1167:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	16	dep	cells	1204:1208	arg1	×2					1227:1228	×2	1227:1228	×2	1227:1228	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	16	dep	cells	1204:1208	arg1	HSC					1211:1213	HSC	1211:1213	HSC	1211:1213	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	6	17	theme	smaller	1049:1055	arg1	size					1064:1067	smaller vessel size	1049:1067	smaller vessel size	1049:1067	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	4	18	theme	coordinate	644:653	arg1	recolonization					682:695	the coordinate hematopoietic and vascular recolonization	640:695	the coordinate hematopoietic and vascular recolonization of the bone shaft	640:713	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	7	19	dep	LSK	1141:1143	arg1	×2					1177:1178	×2	1177:1178	×2	1177:1178	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	19	dep	LSK	1141:1143	arg1	c-Kithi					1167:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	20	dep	HSC	1211:1213	arg1	LSK					1222:1224	Flt3- LSK	1216:1224	Flt3- LSK	1216:1224	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	21	theme	Lin-	1120:1123	arg1	cells					1204:1208	hematopoietic stem cells	1185:1208	hematopoietic stem cells (HSC: Flt3- LSK, ×2)	1185:1229	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	21	theme	Lin-	1120:1123	arg1	number					1110:1115	a much higher number	1096:1115	a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2)	1096:1179	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	2	22	theme	bone	440:443	arg1	formation					445:453	bone formation	440:453	bone formation	440:453	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	10	23	theme	lower	1868:1872	arg1	formation					1889:1897	lower medullary bone formation	1868:1897	lower medullary bone formation	1868:1897	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	0	24	theme	BSP-/-	82:87	arg1	Mice					89:92	BSP-/- Mice	82:92	BSP-/- Mice	82:92	Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
27704558	8	25	theme	BSP	1535:1537	arg1	absence					1524:1530	the absence	1520:1530	the absence of BSP	1520:1537	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	5	26	theme	BSP-/-	803:808	arg1	femurs					810:815	BSP-/- femurs	803:815	BSP-/- femurs	803:815	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	2	27	link	N-linked	388:395	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	5	28	theme	vascular	855:862	arg1	×7					872:873	×7	872:873	×7	872:873	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	5	28	theme	vascular	855:862	arg1	volume					864:869	vascular volume	855:869	vascular volume (×7)	855:874	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	5	29	theme	vessel	831:836	arg1	×4					847:848	×4	847:848	×4	847:848	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	5	29	theme	vessel	831:836	arg1	density					838:844	higher vessel density	824:844	higher vessel density (×4)	824:849	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	4	30	theme	shaft	709:713	arg1	recolonization					682:695	the coordinate hematopoietic and vascular recolonization	640:695	the coordinate hematopoietic and vascular recolonization of the bone shaft	640:713	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	2	31	theme	SIBLING	411:417	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	6	32	from	value	1021:1025	arg1	BSP-/-					1030:1035	BSP-/-	1030:1035	BSP-/-	1030:1035	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	0	33	theme	Bone	0:3	arg1	Revascularization					11:27	Bone Shaft Revascularization	0:27	Bone Shaft Revascularization After Marrow Ablation	0:49	Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
27704558	6	34	theme	BSP+/+	928:933	arg1	mice					935:938	ablated BSP+/+ mice	920:938	ablated BSP+/+ mice	920:938	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	2	35	theme	glycoprotein	397:408	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	2	36	theme	ligand	381:386	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	10	37	theme	bone	1884:1887	arg1	formation					1889:1897	lower medullary bone formation	1868:1897	lower medullary bone formation	1868:1897	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	7	38	theme	faster	1275:1280	arg1	recolonization					1282:1295	a faster recolonization	1273:1295	a faster recolonization	1273:1295	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	1	39	theme	bone	147:150	arg1	organ					152:156	The bone organ	143:156	The bone organ	143:156	The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined.
27704558	9	40	contain	contains	1590:1597	arg1	marrow					1578:1583	unablated BSP-/- femur marrow	1555:1583	unablated BSP-/- femur marrow	1555:1583	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	9	40	contain	contains	1590:1597	arg2	vessels					1610:1616	more blood vessels	1599:1616	more blood vessels	1599:1616	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	15	41	dep	©	2116:2116	arg1	Inc.					2142:2145	Inc.	2142:2145	Inc.	2142:2145	© 2016 Wiley Periodicals, Inc.
27704558	2	42	theme	integrin	364:371	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	0	43	theme	Marrow	35:40	arg1	Ablation					42:49	Marrow Ablation	35:49	Marrow Ablation	35:49	Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
27704558	10	44	dep	vascular	1814:1821	arg1	faster					1807:1812	faster	1807:1812	faster	1807:1812	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	2	45	theme	family	420:425	arg1	sialoprotein					297:308	Bone sialoprotein	292:308	Bone sialoprotein (BSP)	292:314	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	2	45	theme	family	420:425	arg1	member					344:349	a member	342:349	a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis	342:485	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	4	46	theme	BSP+/+	752:757	arg1	mice					770:773	2 month old BSP+/+ and BSP-/- mice	740:773	2 month old BSP+/+ and BSP-/- mice	740:773	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	7	47	theme	higher	1103:1108	arg1	number					1110:1115	a much higher number	1096:1115	a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2)	1096:1179	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	10	48	theme	marrow	1759:1764	arg1	ablation					1766:1773	bone marrow ablation	1754:1773	bone marrow ablation in BSP-/- mice	1754:1788	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	8	49	theme	LSK	1325:1327	arg1	lower					1357:1361	lower	1357:1361	lower	1357:1361	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	8	49	theme	LSK	1325:1327	arg1	proportion					1311:1320	the proportion	1307:1320	the proportion of LSK and HSC within the Lin-	1307:1351	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	4	50	theme	marrow	721:726	arg1	ablation					728:735	marrow ablation	721:735	marrow ablation of 2 month old BSP+/+ and BSP-/- mice	721:773	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	8	51	theme	HSC	1333:1335	arg1	lower					1357:1361	lower	1357:1361	lower	1357:1361	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	8	51	theme	HSC	1333:1335	arg1	proportion					1311:1320	the proportion	1307:1320	the proportion of LSK and HSC within the Lin-	1307:1351	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	8	52	theme	differentiated	1382:1395	arg1	stages					1397:1402	BSP-/- and more differentiated stages	1366:1402	BSP-/- and more differentiated stages were more abundant	1366:1421	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	1	53	theme	vessels	221:227	arg1	activity					173:180	the activity	169:180	the activity of bone tissue, bone marrow, and blood vessels	169:227	The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined.
27704558	9	54	theme	BSP-/-	1565:1570	arg1	marrow					1578:1583	unablated BSP-/- femur marrow	1555:1583	unablated BSP-/- femur marrow	1555:1583	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	2	55	with	member	344:349	arg1	OPN					337:339	OPN	337:339	OPN	337:339	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	2	55	with	member	344:349	arg1	osteopontin					324:334	osteopontin	324:334	osteopontin (OPN)	324:340	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	2	56	gly	glycoprotein	397:408	arg1	glycoprotein					397:408	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	9	57	theme	blood	1604:1608	arg1	vessels					1610:1616	more blood vessels	1599:1616	more blood vessels	1599:1616	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	3	58	theme	BSP-/-	611:616	arg1	mice					618:621	BSP-/- mice	611:621	BSP-/- mice	611:621	In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice.
27704558	1	59	theme	bone	185:188	arg1	tissue					190:195	bone tissue	185:195	bone tissue	185:195	The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined.
27704558	4	60	theme	mice	770:773	arg1	ablation					728:735	marrow ablation	721:735	marrow ablation of 2 month old BSP+/+ and BSP-/- mice	721:773	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	7	61	theme	hematopoietic	1185:1197	arg1	cells					1204:1208	hematopoietic stem cells	1185:1208	hematopoietic stem cells (HSC: Flt3- LSK, ×2)	1185:1229	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	9	62	theme	intact	1643:1648	arg1	shafts					1662:1667	both intact and ablated shafts	1638:1667	both intact and ablated shafts	1638:1667	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	2	63	theme	Bone	292:295	arg1	BSP					311:313	BSP	311:313	BSP	311:313	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	2	63	theme	Bone	292:295	arg1	sialoprotein					297:308	Bone sialoprotein	292:308	Bone sialoprotein (BSP)	292:314	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	2	63	theme	Bone	292:295	arg1	member					344:349	a member	342:349	a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis	342:485	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	8	64	theme	unablated	1444:1452	arg1	bone					1454:1457	unablated bone	1444:1457	unablated bone	1444:1457	However, the proportion of LSK and HSC within the Lin- was lower in BSP-/- and more differentiated stages were more abundant, as also observed in unablated bone, suggesting that hematopoietic differentiation is favored in the absence of BSP.
27704558	6	65	theme	vascular	985:992	arg1	value					1021:1025	the value	1017:1025	the value in BSP-/-	1017:1035	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	6	65	theme	vascular	985:992	arg1	volume					994:999	a vascular volume	983:999	a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants	983:1086	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	9	66	theme	ablated	1654:1660	arg1	shafts					1662:1667	both intact and ablated shafts	1638:1667	both intact and ablated shafts	1638:1667	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	10	67	theme	hematopoietic	1827:1839	arg1	recolonization					1841:1854	a faster vascular and hematopoietic recolonization	1805:1854	recolonization	1841:1854	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	1	68	theme	marrow	203:208	arg1	activity					173:180	the activity	169:180	the activity of bone tissue, bone marrow, and blood vessels	169:227	The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined.
27704558	3	69	theme	rapid	531:535	arg1	formation					537:545	a rapid formation	529:545	a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice	529:621	In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice.
27704558	7	70	theme	Sca-1hi	1159:1165	arg1	×2					1177:1178	×2	1177:1178	×2	1177:1178	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	70	theme	Sca-1hi	1159:1165	arg1	c-Kithi					1167:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	9	71	theme	VEGF	1683:1686	arg1	expression					1669:1678	expression	1669:1678	expression of VEGF and OPN	1669:1694	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	11	72	from	interplay	1930:1938	arg1	part					2004:2007	part	2004:2007	part	2004:2007	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	11	73	theme	angiogenic	2051:2060	arg1	OPN					2071:2073	OPN	2071:2073	OPN	2071:2073	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	11	73	theme	angiogenic	2051:2060	arg1	SIBLING					2062:2068	the angiogenic SIBLING	2047:2068	the angiogenic SIBLING	2047:2068	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	5	74	theme	higher	824:829	arg1	×4					847:848	×4	847:848	×4	847:848	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	5	74	theme	higher	824:829	arg1	density					838:844	higher vessel density	824:844	higher vessel density (×4)	824:849	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	3	75	theme	marrow	505:510	arg1	ablation					512:519	bone marrow ablation	500:519	bone marrow ablation	500:519	In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice.
27704558	7	76	theme	Lin-	1146:1149	arg1	×2					1177:1178	×2	1177:1178	×2	1177:1178	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	76	theme	Lin-	1146:1149	arg1	c-Kithi					1167:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	Lin- IL-7Rα- Sca-1hi c-Kithi	1146:1173	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	9	77	theme	OPN	1692:1694	arg1	expression					1669:1678	expression	1669:1678	expression of VEGF and OPN	1669:1694	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	3	78	theme	bone	560:563	arg1	formation					537:545	a rapid formation	529:545	a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice	529:621	In rodents, bone marrow ablation induces a rapid formation of medullary bone which peaks by ∼8 days (d8) and is blunted in BSP-/- mice.
27704558	5	79	theme	ablated	787:793	arg1	area					795:798	the ablated area	783:798	the ablated area in BSP-/- femurs	783:815	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	6	80	theme	Vessel	889:894	arg1	numbers					896:902	Vessel numbers	889:902	Vessel numbers in the shaft of ablated BSP+/+ mice	889:938	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	14	81	dep	2017	2110:2113	arg1	232					2094:2096	232	2094:2096	232	2094:2096	232: 2528-2537, 2017.
27704558	7	82	theme	LSK	1141:1143	arg1	cells					1204:1208	hematopoietic stem cells	1185:1208	hematopoietic stem cells (HSC: Flt3- LSK, ×2)	1185:1229	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	7	82	theme	LSK	1141:1143	arg1	number					1110:1115	a much higher number	1096:1115	a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2)	1096:1179	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	10	83	theme	medullary	1874:1882	arg1	formation					1889:1897	lower medullary bone formation	1868:1897	lower medullary bone formation	1868:1897	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	6	84	from	numbers	896:902	arg1	shaft					911:915	the shaft	907:915	the shaft of ablated BSP+/+ mice	907:938	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	11	85	theme	VEGF	2038:2041	arg1	OPN					2071:2073	OPN	2071:2073	OPN	2071:2073	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	11	85	theme	VEGF	2038:2041	arg1	expression					2024:2033	higher expression	2017:2033	higher expression of VEGF	2017:2041	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	11	85	theme	VEGF	2038:2041	arg1	SIBLING					2062:2068	the angiogenic SIBLING	2047:2068	the angiogenic SIBLING	2047:2068	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	0	86	theme	Faster	106:111	arg1	Recolonization					127:140	Faster Hematopoietic Recolonization	106:140	Faster Hematopoietic Recolonization	106:140	Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
27704558	5	87	from	area	795:798	arg1	femurs					810:815	BSP-/- femurs	803:815	BSP-/- femurs	803:815	At d3, the ablated area in BSP-/- femurs showed higher vessel density (×4) and vascular volume (×7) than BSP+/+.
27704558	6	88	theme	BSP-/-	948:953	arg1	values					955:960	BSP-/- values	948:960	BSP-/- values	948:960	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	11	89	theme	BSP	1914:1916	arg1	lack					1906:1909	lack	1906:1909	lack of BSP	1906:1916	Thus, lack of BSP affects the interplay between hematopoiesis, angiogenesis, and osteogenesis, maybe in part through higher expression of VEGF and the angiogenic SIBLING, OPN.
27704558	4	90	theme	bone	704:707	arg1	shaft					709:713	the bone shaft	700:713	the bone shaft	700:713	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	0	91	theme	Shaft	5:9	arg1	Revascularization					11:27	Bone Shaft Revascularization	0:27	Bone Shaft Revascularization After Marrow Ablation	0:49	Bone Shaft Revascularization After Marrow Ablation Is Dramatically Accelerated in BSP-/- Mice, Along With Faster Hematopoietic Recolonization.
27704558	6	92	theme	mice	935:938	arg1	shaft					911:915	the shaft	907:915	the shaft of ablated BSP+/+ mice	907:938	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	4	93	theme	hematopoietic	655:667	arg1	recolonization					682:695	the coordinate hematopoietic and vascular recolonization	640:695	the coordinate hematopoietic and vascular recolonization of the bone shaft	640:713	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	6	94	theme	ablated	920:926	arg1	mice					935:938	ablated BSP+/+ mice	920:938	ablated BSP+/+ mice	920:938	Vessel numbers in the shaft of ablated BSP+/+ mice reached BSP-/- values only by d8, but with a vascular volume which was twice the value in BSP-/-, reflecting smaller vessel size in ablated mutants.
27704558	2	95	theme	N-linked	388:395	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	4	96	theme	vascular	673:680	arg1	recolonization					682:695	the coordinate hematopoietic and vascular recolonization	640:695	the coordinate hematopoietic and vascular recolonization of the bone shaft	640:713	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	2	97	theme	binding	373:379	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	9	98	theme	unablated	1555:1563	arg1	marrow					1578:1583	unablated BSP-/- femur marrow	1555:1583	unablated BSP-/- femur marrow	1555:1583	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	2	99	theme	small	358:362	arg1	family					420:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	the small integrin binding ligand N-linked glycoprotein (SIBLING) family	354:425	Bone sialoprotein (BSP) is with osteopontin (OPN) a member of the small integrin binding ligand N-linked glycoprotein (SIBLING) family, involved in bone formation, hematopoiesis and angiogenesis.
27704558	9	100	theme	femur	1572:1576	arg1	marrow					1578:1583	unablated BSP-/- femur marrow	1555:1583	unablated BSP-/- femur marrow	1555:1583	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
27704558	4	101	theme	old	748:750	arg1	mice					770:773	2 month old BSP+/+ and BSP-/- mice	740:773	2 month old BSP+/+ and BSP-/- mice	740:773	We investigated the coordinate hematopoietic and vascular recolonization of the bone shaft after marrow ablation of 2 month old BSP+/+ and BSP-/- mice.
27704558	10	102	theme	bone	1754:1757	arg1	marrow					1759:1764	bone marrow	1754:1764	bone marrow ablation in BSP-/- mice	1754:1788	In conclusion, bone marrow ablation in BSP-/- mice is followed by a faster vascular and hematopoietic recolonization, along with lower medullary bone formation.
27704558	1	103	theme	blood	215:219	arg1	vessels					221:227	blood vessels	215:227	blood vessels	215:227	The bone organ integrates the activity of bone tissue, bone marrow, and blood vessels and the factors ensuring this coordination remain ill defined.
27704558	7	104	theme	BSP-/-	1247:1252	arg1	marrow					1254:1259	BSP-/- marrow	1247:1259	BSP-/- marrow	1247:1259	At d6, a much higher number of Lin- (×3) as well as LSK (Lin- IL-7Rα- Sca-1hi c-Kithi , ×2) and hematopoietic stem cells (HSC: Flt3- LSK, ×2) were counted in BSP-/- marrow, indicating a faster recolonization.
27704558	9	105	theme	more	1599:1602	arg1	vessels					1610:1616	more blood vessels	1599:1616	more blood vessels	1599:1616	Interestingly, unablated BSP-/- femur marrow also contains more blood vessels than BSP+/+, and in both intact and ablated shafts expression of VEGF and OPN are higher, and DMP1 lower in the mutants.
30761158	5	0	theme	CD16-F	749:754	arg1	antibodies					771:780	CD16-F(ab')2 blocking antibodies	749:780	CD16-F(ab')2 blocking antibodies	749:780	Inhibiting FcγRIIIb using CD16-F(ab')2 blocking antibodies resulted in substantially enhanced ADCC.
30761158	7	1	theme	decoy	1079:1083	arg1	receptor					1085:1092	a decoy receptor	1077:1092	a decoy receptor	1077:1092	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	6	2	theme	target	1009:1014	arg1	cells					1016:1020	the opsonized target cells	995:1020	the opsonized target cells	995:1020	ADCC was completely dependent on FcγRIIa (CD32a) and the enhanced ADCC seen after FcγRIIIb blockade therefore suggested that FcγRIIIb was competing with FcγRIIa for IgG on the opsonized target cells.
30761158	2	3	theme	-anchored	312:320	arg1	it					271:272	it	271:272	it	271:272	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	2	3	theme	-anchored	312:320	arg1	molecule					322:329	a glycophosphatidyl inositol (GPI) -anchored molecule	277:329	a glycophosphatidyl inositol (GPI) -anchored molecule	277:329	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	10	4	theme	neutrophil	1725:1734	arg1	ADCC					1736:1739	neutrophil ADCC	1725:1739	neutrophil ADCC toward tumor cells	1725:1758	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	8	5	theme	FCGR3B	1283:1288	arg1	copy					1275:1278	one copy	1271:1278	one copy of FCGR3B	1271:1288	Individuals with one copy of FCGR3B showed higher levels of ADCC compared to those with two or more copies.
30761158	9	6	theme	killer	1462:1467	arg1	ADCC					1479:1482	FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC	1427:1482	FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC	1427:1482	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	8	7	theme	higher	1297:1302	arg1	levels					1304:1309	higher levels	1297:1309	higher levels of ADCC	1297:1317	Individuals with one copy of FCGR3B showed higher levels of ADCC compared to those with two or more copies.
30761158	4	8	theme	FcγRIIIb	549:556	arg1	role					541:544	the role	537:544	the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR)	537:720	Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR).
30761158	7	9	theme	gene	1169:1172	arg1	numbers					1179:1185	different gene copy numbers	1159:1185	different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression	1159:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	9	10	theme	chain	1574:1578	arg1	Fc-region					1580:1588	the IgG1 heavy chain Fc-region	1559:1588	the IgG1 heavy chain Fc-region	1559:1588	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	8	11	theme	ADCC	1314:1317	arg1	levels					1304:1309	higher levels	1297:1309	higher levels of ADCC	1297:1317	Individuals with one copy of FCGR3B showed higher levels of ADCC compared to those with two or more copies.
30761158	7	12	with	individuals	1142:1152	arg1	numbers					1179:1185	different gene copy numbers	1159:1185	different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression	1159:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	4	13	theme	cellular	584:591	arg1	ADCC					607:610	ADCC	607:610	ADCC	607:610	Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR).
30761158	4	13	theme	cellular	584:591	arg1	cytotoxicity					593:604	antibody-dependent cellular cytotoxicity	565:604	antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR)	565:720	Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR).
30761158	7	14	theme	copy	1174:1177	arg1	numbers					1179:1185	different gene copy numbers	1159:1185	different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression	1159:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	8	15	with	Individuals	1254:1264	arg1	copy					1275:1278	one copy	1271:1278	one copy of FCGR3B	1271:1288	Individuals with one copy of FCGR3B showed higher levels of ADCC compared to those with two or more copies.
30761158	9	16	theme	Fc-region	1580:1588	arg1	position					1542:1549	position N297	1542:1554	position N297 of the IgG1 heavy chain Fc-region	1542:1588	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	3	17	theme	microbes	480:487	arg1	phagocytosis					445:456	phagocytosis	445:456	phagocytosis of antibody-opsonized microbes by human neutrophils	445:508	Nevertheless, FcγRIIIb can cooperate with other FcγR to promote phagocytosis of antibody-opsonized microbes by human neutrophils.
30761158	4	18	theme	antibody-dependent	565:582	arg1	ADCC					607:610	ADCC	607:610	ADCC	607:610	Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR).
30761158	4	18	theme	antibody-dependent	565:582	arg1	cytotoxicity					593:604	antibody-dependent cellular cytotoxicity	565:604	antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR)	565:720	Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR).
30761158	7	19	theme	neutrophil	1054:1063	arg1	FcγRIIIb					1065:1072	neutrophil FcγRIIIb	1054:1072	neutrophil FcγRIIIb	1054:1072	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	5	20	theme	enhanced	808:815	arg1	ADCC					817:820	substantially enhanced ADCC	794:820	substantially enhanced ADCC	794:820	Inhibiting FcγRIIIb using CD16-F(ab')2 blocking antibodies resulted in substantially enhanced ADCC.
30761158	2	21	theme	intracellular	349:361	arg1	motifs					373:378	intracellular signaling motifs	349:378	intracellular signaling motifs	349:378	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	7	22	theme	different	1159:1167	arg1	numbers					1179:1185	different gene copy numbers	1159:1185	different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression	1159:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	7	23	theme	FcγRIIIb	1065:1072	arg1	function					1042:1049	the function	1038:1049	the function of neutrophil FcγRIIIb as a decoy receptor	1038:1092	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	9	24	theme	-dependent	1443:1452	arg1	ADCC					1479:1482	FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC	1427:1482	FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC	1427:1482	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	4	25	theme	cancer	641:646	arg1	cells					648:652	solid cancer cells	635:652	solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR)	635:720	Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR).
30761158	5	26	theme	blocking	762:769	arg1	antibodies					771:780	CD16-F(ab')2 blocking antibodies	749:780	CD16-F(ab')2 blocking antibodies	749:780	Inhibiting FcγRIIIb using CD16-F(ab')2 blocking antibodies resulted in substantially enhanced ADCC.
30761158	7	27	from	individuals	1142:1152	arg1	neutrophils					1125:1135	neutrophils	1125:1135	neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression	1125:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	9	28	theme	decreased	1596:1604	arg1	ADCC					1606:1609	decreased ADCC	1596:1609	decreased ADCC as compared to regularly fucosylated antibodies	1596:1657	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	10	29	theme	negative	1703:1710	arg1	regulator					1712:1720	a negative regulator	1701:1720	a negative regulator of neutrophil ADCC toward tumor cells	1701:1758	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	10	29	theme	negative	1703:1710	arg1	FcγRIIIb					1689:1696	FcγRIIIb	1689:1696	FcγRIIIb	1689:1696	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	10	30	theme	potential	1766:1774	arg1	target					1776:1781	a potential target	1764:1781	a potential target for enhancing tumor cell destruction by neutrophils	1764:1833	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	10	30	theme	potential	1766:1774	arg1	FcγRIIIb					1689:1696	FcγRIIIb	1689:1696	FcγRIIIb	1689:1696	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	9	31	theme	heavy	1568:1572	arg1	chain					1574:1578	the IgG1 heavy chain	1559:1578	the IgG1 heavy chain Fc-region	1559:1588	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	9	32	theme	fucosylation	1503:1514	arg1	lack					1495:1498	the lack	1491:1498	the lack of fucosylation on the N-linked glycan	1491:1537	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	9	33	gly	fucosylated	1636:1646	arg1	antibodies					1648:1657	regularly fucosylated antibodies	1626:1657	regularly fucosylated antibodies	1626:1657	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	0	34	theme	Antibody-Dependent	19:36	arg1	Destruction					38:48	Antibody-Dependent Destruction	19:48	Antibody-Dependent Destruction of Cancer Cells by Human Neutrophils	19:85	FcγRIIIb Restricts Antibody-Dependent Destruction of Cancer Cells by Human Neutrophils.
30761158	1	35	theme	low-affinity	108:119	arg1	CD16b					144:148	CD16b	144:148	CD16b	144:148	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear.
30761158	1	35	theme	low-affinity	108:119	arg1	FcγRIIIb					134:141	the low-affinity IgG-receptor FcγRIIIb	104:141	the low-affinity IgG-receptor FcγRIIIb (CD16b)	104:149	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear.
30761158	9	36	theme	cell	1474:1477	arg1	ADCC					1479:1482	FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC	1427:1482	FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC	1427:1482	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	1	37	theme	human	198:202	arg1	granulocytes					204:215	human granulocytes	198:215	human granulocytes	198:215	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear.
30761158	0	38	theme	Cancer	53:58	arg1	Cells					60:64	Cancer Cells	53:64	Cancer Cells	53:64	FcγRIIIb Restricts Antibody-Dependent Destruction of Cancer Cells by Human Neutrophils.
30761158	3	39	theme	antibody-opsonized	461:478	arg1	microbes					480:487	antibody-opsonized microbes	461:487	antibody-opsonized microbes	461:487	Nevertheless, FcγRIIIb can cooperate with other FcγR to promote phagocytosis of antibody-opsonized microbes by human neutrophils.
30761158	6	40	theme	opsonized	999:1007	arg1	cells					1016:1020	the opsonized target cells	995:1020	the opsonized target cells	995:1020	ADCC was completely dependent on FcγRIIa (CD32a) and the enhanced ADCC seen after FcγRIIIb blockade therefore suggested that FcγRIIIb was competing with FcγRIIa for IgG on the opsonized target cells.
30761158	9	41	link	N-linked	1523:1530	arg1	glycan					1532:1537	the N-linked glycan	1519:1537	the N-linked glycan	1519:1537	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	4	42	theme	solid	635:639	arg1	cells					648:652	solid cancer cells	635:652	solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR)	635:720	Here we have investigated the role of FcγRIIIb during antibody-dependent cellular cytotoxicity (ADCC) by neutrophils toward solid cancer cells coated with either trastuzumab (anti-HER2) or cetuximab (anti-EGFR).
30761158	9	43	theme	therapeutic	1384:1394	arg1	antibodies					1396:1405	therapeutic antibodies	1384:1405	therapeutic antibodies	1384:1405	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	6	44	theme	FcγRIIIb	905:912	arg1	blockade					914:921	FcγRIIIb blockade	905:921	FcγRIIIb blockade	905:921	ADCC was completely dependent on FcγRIIa (CD32a) and the enhanced ADCC seen after FcγRIIIb blockade therefore suggested that FcγRIIIb was competing with FcγRIIa for IgG on the opsonized target cells.
30761158	9	45	dep	ADCC	1606:1609	arg1	compared					1614:1621	compared	1614:1621	compared to regularly fucosylated antibodies	1614:1657	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	2	46	contain	have	344:347	arg1	it					271:272	it	271:272	it	271:272	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	2	46	contain	have	344:347	arg2	motifs					373:378	intracellular signaling motifs	349:378	intracellular signaling motifs	349:378	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	2	46	contain	have	344:347	arg1	molecule					322:329	a glycophosphatidyl inositol (GPI) -anchored molecule	277:329	a glycophosphatidyl inositol (GPI) -anchored molecule	277:329	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	9	47	theme	IgG1	1563:1566	arg1	chain					1574:1578	the IgG1 heavy chain	1559:1578	the IgG1 heavy chain Fc-region	1559:1588	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	3	48	theme	other	423:427	arg1	FcγR					429:432	other FcγR	423:432	other FcγR	423:432	Nevertheless, FcγRIIIb can cooperate with other FcγR to promote phagocytosis of antibody-opsonized microbes by human neutrophils.
30761158	9	49	theme	fucosylated	1636:1646	arg1	antibodies					1648:1657	regularly fucosylated antibodies	1626:1657	regularly fucosylated antibodies	1626:1657	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	1	50	theme	IgG-receptor	121:132	arg1	CD16b					144:148	CD16b	144:148	CD16b	144:148	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear.
30761158	1	50	theme	IgG-receptor	121:132	arg1	FcγRIIIb					134:141	the low-affinity IgG-receptor FcγRIIIb	104:141	the low-affinity IgG-receptor FcγRIIIb (CD16b)	104:149	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear.
30761158	0	51	theme	Cells	60:64	arg1	Destruction					38:48	Antibody-Dependent Destruction	19:48	Antibody-Dependent Destruction of Cancer Cells by Human Neutrophils	19:85	FcγRIIIb Restricts Antibody-Dependent Destruction of Cancer Cells by Human Neutrophils.
30761158	1	52	theme	FcγRIIIb	134:141	arg1	clear					225:229	clear	225:229	clear	225:229	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear.
30761158	1	52	theme	FcγRIIIb	134:141	arg1	function					92:99	The function	88:99	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes,	88:216	The function of the low-affinity IgG-receptor FcγRIIIb (CD16b), which is uniquely and abundantly expressed on human granulocytes, is not clear.
30761158	10	53	theme	cell	1803:1806	arg1	destruction					1808:1818	tumor cell destruction	1797:1818	tumor cell destruction by neutrophils	1797:1833	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	2	54	theme	Fcγ	249:251	arg1	FcγR					264:267	FcγR	264:267	FcγR	264:267	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	2	54	theme	Fcγ	249:251	arg1	receptors					253:261	the other Fcγ receptors	239:261	the other Fcγ receptors (FcγR)	239:268	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	9	55	theme	N-linked	1523:1530	arg1	glycan					1532:1537	the N-linked glycan	1519:1537	the N-linked glycan	1519:1537	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	7	56	theme	FcγRIIIb	1233:1240	arg1	expression					1242:1251	surface FcγRIIIb expression	1225:1251	surface FcγRIIIb expression	1225:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	10	57	theme	tumor	1797:1801	arg1	destruction					1808:1818	tumor cell destruction	1797:1818	tumor cell destruction by neutrophils	1797:1833	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	2	58	theme	other	243:247	arg1	FcγR					264:267	FcγR	264:267	FcγR	264:267	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	2	58	theme	other	243:247	arg1	receptors					253:261	the other Fcγ receptors	239:261	the other Fcγ receptors (FcγR)	239:268	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	7	59	theme	expression	1242:1251	arg1	levels					1215:1220	different levels	1205:1220	different levels of surface FcγRIIIb expression	1205:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	9	60	from	lack	1495:1498	arg1	glycan					1532:1537	the N-linked glycan	1519:1537	the N-linked glycan	1519:1537	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	9	61	theme	natural	1454:1460	arg1	NK					1470:1471	NK	1470:1471	NK	1470:1471	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	9	61	theme	natural	1454:1460	arg1	killer					1462:1467	natural killer	1454:1467	FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC	1427:1482	Finally, we show that therapeutic antibodies intended to improve FcγRIIIa (CD16a)-dependent natural killer (NK) cell ADCC due to the lack of fucosylation on the N-linked glycan at position N297 of the IgG1 heavy chain Fc-region, show decreased ADCC as compared to regularly fucosylated antibodies.
30761158	7	62	theme	FCGR3B	1190:1195	arg1	numbers					1179:1185	different gene copy numbers	1159:1185	different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression	1159:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	2	63	theme	signaling	363:371	arg1	motifs					373:378	intracellular signaling motifs	349:378	intracellular signaling motifs	349:378	Unlike the other Fcγ receptors (FcγR), it is a glycophosphatidyl inositol (GPI) -anchored molecule and does not have intracellular signaling motifs.
30761158	10	64	theme	tumor	1748:1752	arg1	cells					1754:1758	tumor cells	1748:1758	tumor cells	1748:1758	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	3	65	theme	human	492:496	arg1	neutrophils					498:508	human neutrophils	492:508	human neutrophils	492:508	Nevertheless, FcγRIIIb can cooperate with other FcγR to promote phagocytosis of antibody-opsonized microbes by human neutrophils.
30761158	0	66	theme	Human	69:73	arg1	Neutrophils					75:85	Human Neutrophils	69:85	Human Neutrophils	69:85	FcγRIIIb Restricts Antibody-Dependent Destruction of Cancer Cells by Human Neutrophils.
30761158	6	67	theme	enhanced	880:887	arg1	ADCC					889:892	the enhanced ADCC	876:892	the enhanced ADCC seen after FcγRIIIb blockade	876:921	ADCC was completely dependent on FcγRIIa (CD32a) and the enhanced ADCC seen after FcγRIIIb blockade therefore suggested that FcγRIIIb was competing with FcγRIIa for IgG on the opsonized target cells.
30761158	10	68	theme	ADCC	1736:1739	arg1	target					1776:1781	a potential target	1764:1781	a potential target for enhancing tumor cell destruction by neutrophils	1764:1833	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	10	68	theme	ADCC	1736:1739	arg1	regulator					1712:1720	a negative regulator	1701:1720	a negative regulator of neutrophil ADCC toward tumor cells	1701:1758	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	10	68	theme	ADCC	1736:1739	arg1	FcγRIIIb					1689:1696	FcγRIIIb	1689:1696	FcγRIIIb	1689:1696	Together, these data confirm FcγRIIIb as a negative regulator of neutrophil ADCC toward tumor cells and a potential target for enhancing tumor cell destruction by neutrophils.
30761158	7	69	theme	surface	1225:1231	arg1	expression					1242:1251	surface FcγRIIIb expression	1225:1251	surface FcγRIIIb expression	1225:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30761158	7	70	theme	different	1205:1213	arg1	levels					1215:1220	different levels	1205:1220	different levels of surface FcγRIIIb expression	1205:1251	Interestingly, the function of neutrophil FcγRIIIb as a decoy receptor was further supported by using neutrophils from individuals with different gene copy numbers of FCGR3B causing different levels of surface FcγRIIIb expression.
30181542	7	0	theme	therapeutic	1205:1215	arg1	antibodies					1217:1226	therapeutic antibodies	1205:1226	therapeutic antibodies	1205:1226	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	3	1	from	production	372:381	arg1	milk					421:424	the milk	417:424	the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL)	417:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	6	2	theme	B-cell	1029:1034	arg1	lymphomas					1036:1044	B-cell lymphomas	1029:1044	B-cell lymphomas	1029:1044	Accordingly, our recombinant mAb demonstrated a superior efficacy over Rituxan against B-cell lymphomas in severe combined immunodeficiency mice.
30181542	5	3	theme	higher	849:854	arg1	affinity					864:871	a higher binding affinity	847:871	a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity	847:939	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	7	4	theme	antibodies	1217:1226	arg1	production					1191:1200	cost-competitive, large-scale production	1161:1200	cost-competitive, large-scale production of therapeutic antibodies	1161:1226	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	3	5	from	yield	453:457	arg1	milk					421:424	the milk	417:424	the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL)	417:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	3	5	from	yield	453:457	arg1	cattle					440:445	transgenic cattle	429:445	transgenic cattle (at a yield of up to ~6.8 mg/mL)	429:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	5	6	theme	binding	856:862	arg1	affinity					864:871	a higher binding affinity	847:871	a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity	847:939	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	2	7	from	availability	293:304	arg1	countries					320:328	developing countries	309:328	developing countries	309:328	However, further application of Rituxan faces challenges of high production cost, which limits its availability in developing countries.
30181542	1	8	used	used	145:148	arg2	mAb					100:102	mAb	100:102	mAb	100:102	The monoclonal antibody (mAb) against CD20 known as Rituxan is widely used to treat autoimmune diseases and lymphomas.
30181542	1	8	used	used	145:148	arg2	antibody					90:97	The monoclonal antibody	75:97	The monoclonal antibody (mAb) against CD20 known as Rituxan	75:133	The monoclonal antibody (mAb) against CD20 known as Rituxan is widely used to treat autoimmune diseases and lymphomas.
30181542	5	9	theme	cellular	919:926	arg1	cytotoxicity					928:939	a greater antibody-dependent cellular cytotoxicity	890:939	a greater antibody-dependent cellular cytotoxicity	890:939	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	6	10	theme	recombinant	959:969	arg1	mAb					971:973	our recombinant mAb	955:973	our recombinant mAb	955:973	Accordingly, our recombinant mAb demonstrated a superior efficacy over Rituxan against B-cell lymphomas in severe combined immunodeficiency mice.
30181542	7	11	dep	cost-competitive	1161:1176	arg1	large-scale					1179:1189	large-scale	1179:1189	large-scale	1179:1189	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	2	12	theme	cost	270:273	arg1	challenges					240:249	challenges	240:249	challenges	240:249	However, further application of Rituxan faces challenges of high production cost, which limits its availability in developing countries.
30181542	5	13	theme	complement-dependent	777:796	arg1	cytotoxicity					798:809	complement-dependent cytotoxicity	777:809	complement-dependent cytotoxicity	777:809	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	2	14	theme	production	259:268	arg1	cost					270:273	high production cost	254:273	high production cost	254:273	However, further application of Rituxan faces challenges of high production cost, which limits its availability in developing countries.
30181542	3	15	theme	recombinant	388:398	arg1	mAb					410:412	a recombinant anti-CD20 mAb	386:412	a recombinant anti-CD20 mAb	386:412	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	3	16	theme	mAb	410:412	arg1	production					372:381	large production	366:381	large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL)	366:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	5	17	theme	Functional	683:692	arg1	study					694:698	Functional study	683:698	Functional study	683:698	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	4	18	with	Rituxan	612:618	arg1	differences					636:646	only minor differences	625:646	only minor differences in N-linked glycosylation pattern	625:680	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	1	19	theme	monoclonal	79:88	arg1	mAb					100:102	mAb	100:102	mAb	100:102	The monoclonal antibody (mAb) against CD20 known as Rituxan is widely used to treat autoimmune diseases and lymphomas.
30181542	1	19	theme	monoclonal	79:88	arg1	antibody					90:97	The monoclonal antibody	75:97	The monoclonal antibody (mAb) against CD20 known as Rituxan	75:133	The monoclonal antibody (mAb) against CD20 known as Rituxan is widely used to treat autoimmune diseases and lymphomas.
30181542	6	20	theme	combined	1056:1063	arg1	immunodeficiency					1065:1080	severe combined immunodeficiency	1049:1080	severe combined immunodeficiency mice	1049:1085	Accordingly, our recombinant mAb demonstrated a superior efficacy over Rituxan against B-cell lymphomas in severe combined immunodeficiency mice.
30181542	5	21	theme	similar	734:740	arg1	capacities					762:771	similar target-cell binding capacities	734:771	similar target-cell binding capacities	734:771	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	6	22	theme	immunodeficiency	1065:1080	arg1	mice					1082:1085	severe combined immunodeficiency mice	1049:1085	severe combined immunodeficiency mice	1049:1085	Accordingly, our recombinant mAb demonstrated a superior efficacy over Rituxan against B-cell lymphomas in severe combined immunodeficiency mice.
30181542	3	23	theme	recovery	491:498	arg1	rate					500:503	~80% recovery rate	486:503	~80% recovery rate	486:503	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	6	24	theme	severe	1049:1054	arg1	immunodeficiency					1065:1080	severe combined immunodeficiency	1049:1080	severe combined immunodeficiency mice	1049:1085	Accordingly, our recombinant mAb demonstrated a superior efficacy over Rituxan against B-cell lymphomas in severe combined immunodeficiency mice.
30181542	1	25	theme	autoimmune	159:168	arg1	diseases					170:177	autoimmune diseases	159:177	autoimmune diseases	159:177	The monoclonal antibody (mAb) against CD20 known as Rituxan is widely used to treat autoimmune diseases and lymphomas.
30181542	5	26	theme	target-cell	742:752	arg1	capacities					762:771	similar target-cell binding capacities	734:771	similar target-cell binding capacities	734:771	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	4	27	theme	glycosylation	660:672	arg1	pattern					674:680	N-linked glycosylation pattern	651:680	N-linked glycosylation pattern	651:680	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	3	28	theme	anti-CD20	400:408	arg1	mAb					410:412	a recombinant anti-CD20 mAb	386:412	a recombinant anti-CD20 mAb	386:412	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	5	29	theme	binding	754:760	arg1	capacities					762:771	similar target-cell binding capacities	734:771	similar target-cell binding capacities	734:771	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	3	30	theme	~80	486:488	arg1	%					489:489	%	489:489	%	489:489	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	3	31	theme	new	349:351	arg1	approach					353:360	a new approach	347:360	a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL)	347:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	5	32	theme	greater	892:898	arg1	cytotoxicity					928:939	a greater antibody-dependent cellular cytotoxicity	890:939	a greater antibody-dependent cellular cytotoxicity	890:939	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	3	33	theme	%	489:489	arg1	rate					500:503	~80% recovery rate	486:503	~80% recovery rate	486:503	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	3	34	theme	transgenic	429:438	arg1	cattle					440:445	transgenic cattle	429:445	transgenic cattle (at a yield of up to ~6.8 mg/mL)	429:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	7	35	theme	cost-competitive	1161:1176	arg1	production					1191:1200	cost-competitive, large-scale production	1161:1200	cost-competitive, large-scale production of therapeutic antibodies	1161:1226	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	3	36	theme	%	512:512	arg1	purity					514:519	>99% purity	509:519	>99% purity	509:519	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	7	37	theme	transgenic	1122:1131	arg1	model					1151:1155	a novel model	1143:1155	a novel model for cost-competitive, large-scale production of therapeutic antibodies	1143:1226	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	7	37	theme	transgenic	1122:1131	arg1	cattle					1133:1138	transgenic cattle	1122:1138	transgenic cattle	1122:1138	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	0	38	theme	monoclonal	31:40	arg1	antibody					42:49	anti-CD20 monoclonal antibody	21:49	anti-CD20 monoclonal antibody from transgenic cattle	21:72	A novel glycosylated anti-CD20 monoclonal antibody from transgenic cattle.
30181542	7	39	theme	novel	1145:1149	arg1	model					1151:1155	a novel model	1143:1155	a novel model for cost-competitive, large-scale production of therapeutic antibodies	1143:1226	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	7	39	theme	novel	1145:1149	arg1	cattle					1133:1138	transgenic cattle	1122:1138	transgenic cattle	1122:1138	Taken together, our data supports transgenic cattle as a novel model for cost-competitive, large-scale production of therapeutic antibodies.
30181542	4	40	theme	recombinant	560:570	arg1	mAb					572:574	our recombinant mAb	556:574	our recombinant mAb	556:574	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	3	41	theme	large	366:370	arg1	production					372:381	large production	366:381	large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL)	366:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	0	42	from	cattle	67:72	arg1	antibody					42:49	anti-CD20 monoclonal antibody	21:49	anti-CD20 monoclonal antibody from transgenic cattle	21:72	A novel glycosylated anti-CD20 monoclonal antibody from transgenic cattle.
30181542	2	43	theme	further	203:209	arg1	application					211:221	further application	203:221	further application of Rituxan	203:232	However, further application of Rituxan faces challenges of high production cost, which limits its availability in developing countries.
30181542	3	44	from	milk	421:424	arg1	yield					453:457	a yield	451:457	a yield of up to ~6.8 mg/mL	451:477	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	3	45	theme	>99	509:511	arg1	%					512:512	%	512:512	%	512:512	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	4	46	theme	minor	630:634	arg1	differences					636:646	only minor differences	625:646	only minor differences in N-linked glycosylation pattern	625:680	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	4	47	theme	N-linked	651:658	arg1	pattern					674:680	N-linked glycosylation pattern	651:680	N-linked glycosylation pattern	651:680	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	2	48	theme	developing	309:318	arg1	countries					320:328	developing countries	309:328	developing countries	309:328	However, further application of Rituxan faces challenges of high production cost, which limits its availability in developing countries.
30181542	5	49	theme	antibody-dependent	900:917	arg1	cytotoxicity					928:939	a greater antibody-dependent cellular cytotoxicity	890:939	a greater antibody-dependent cellular cytotoxicity	890:939	Functional study showed that, while our mAb shared similar target-cell binding capacities and complement-dependent cytotoxicity with Rituxan, our product exhibited a higher binding affinity for FcγRIIIα and a greater antibody-dependent cellular cytotoxicity.
30181542	4	50	theme	Crystallography	522:536	arg1	study					538:542	Crystallography study	522:542	Crystallography study	522:542	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	2	51	theme	high	254:257	arg1	cost					270:273	high production cost	254:273	high production cost	254:273	However, further application of Rituxan faces challenges of high production cost, which limits its availability in developing countries.
30181542	4	52	link	N-linked	651:658	arg1	pattern					674:680	N-linked glycosylation pattern	651:680	N-linked glycosylation pattern	651:680	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	4	53	from	differences	636:646	arg1	pattern					674:680	N-linked glycosylation pattern	651:680	N-linked glycosylation pattern	651:680	Crystallography study showed that our recombinant mAb is structurally nearly identical to Rituxan with only minor differences in N-linked glycosylation pattern.
30181542	3	54	theme	cattle	440:445	arg1	milk					421:424	the milk	417:424	the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL)	417:478	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	3	55	theme	up	462:463	arg1	yield					453:457	a yield	451:457	a yield of up to ~6.8 mg/mL	451:477	Here, we report a new approach for large production of a recombinant anti-CD20 mAb in the milk of transgenic cattle (at a yield of up to ~6.8 mg/mL), with ~80% recovery rate and >99% purity.
30181542	6	56	theme	superior	990:997	arg1	efficacy					999:1006	a superior efficacy	988:1006	a superior efficacy over Rituxan against B-cell lymphomas	988:1044	Accordingly, our recombinant mAb demonstrated a superior efficacy over Rituxan against B-cell lymphomas in severe combined immunodeficiency mice.
30181542	0	57	theme	transgenic	56:65	arg1	cattle					67:72	transgenic cattle	56:72	transgenic cattle	56:72	A novel glycosylated anti-CD20 monoclonal antibody from transgenic cattle.
30181542	2	58	theme	Rituxan	226:232	arg1	application					211:221	further application	203:221	further application of Rituxan	203:232	However, further application of Rituxan faces challenges of high production cost, which limits its availability in developing countries.
29263309	8	0	from	tubules	1404:1410	arg1	upregulation					1358:1369	upregulation	1358:1369	upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion	1358:1438	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	7	1	theme	subsequent	1055:1064	arg1	adhesion					1076:1083	subsequent bacterial adhesion	1055:1083	subsequent bacterial adhesion	1055:1083	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	7	2	theme	intracellular	1158:1170	arg1	signaling					1172:1180	C5aR1-mediated intracellular signaling	1143:1180	C5aR1-mediated intracellular signaling	1143:1180	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	5	3	from	surface	748:754	arg1	mice					834:837	these mice	828:837	these mice	828:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	3	from	surface	748:754	arg1	expression					643:652	reduced expression	635:652	reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	635:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	6	4	theme	tubular	927:933	arg1	epithelium					935:944	renal tubular epithelium	921:944	renal tubular epithelium	921:944	Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium.
29263309	5	5	dep	residues	677:684	arg1	Man					687:689	Man	687:689	Man; a ligand for type 1 fimbriae of E. coli	687:730	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	6	6	theme	Confocal	840:847	arg1	microscopy					849:858	Confocal microscopy	840:858	Confocal microscopy	840:858	Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium.
29263309	7	7	theme	bacterial	1066:1074	arg1	adhesion					1076:1083	subsequent bacterial adhesion	1055:1083	subsequent bacterial adhesion	1055:1083	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	7	8	theme	Man	1002:1004	arg1	expression					1006:1015	Man expression	1002:1015	Man expression in renal tubular epithelial cells	1002:1049	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	4	9	theme	C5aR1	539:543	arg1	inhibition					525:534	pharmacologic inhibition	511:534	pharmacologic inhibition of C5aR1	511:543	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	3	10	theme	bacterial	294:302	arg1	adhesion/colonization					304:324	bacterial adhesion/colonization	294:324	bacterial adhesion/colonization of renal tubular epithelium	294:352	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	1	11	gly	glycosylated	154:165	arg1	protein					167:173	an N-linked glycosylated protein	142:173	also an N-linked glycosylated protein	137:173	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	5	12	from	mice	834:837	arg1	surface					748:754	the luminal surface	736:754	the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	736:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	4	13	theme	kidney	427:432	arg1	infection					434:442	acute kidney infection	421:442	acute kidney infection	421:442	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	8	14	from	upregulation	1358:1369	arg1	tubules					1404:1410	renal tubules	1398:1410	renal tubules	1398:1410	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	4	15	theme	bladder	555:561	arg1	inoculation					563:573	bladder inoculation	555:573	bladder inoculation with uropathogenic E. coli (UPEC)	555:607	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	3	16	theme	C5aR1	285:289	arg1	role					277:280	the role	273:280	the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium	273:352	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	4	17	theme	acute	421:425	arg1	infection					434:442	acute kidney infection	421:442	acute kidney infection	421:442	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	1	18	link	N-linked	145:152	arg1	protein					167:173	an N-linked glycosylated protein	142:173	also an N-linked glycosylated protein	137:173	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	1	19	theme	C5a	70:72	arg1	receptor					74:81	C5a receptor 1	70:83	C5a receptor 1 (C5aR1)	70:91	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	1	19	theme	C5a	70:72	arg1	C5aR1					86:90	C5aR1	86:90	C5aR1	86:90	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	1	19	theme	C5a	70:72	arg1	receptor					116:123	a G protein-coupled receptor	96:123	a G protein-coupled receptor for C5a and also an N-linked glycosylated protein	96:173	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	5	20	theme	early	801:805	arg1	colonization					812:823	early UPEC colonization	801:823	early UPEC colonization	801:823	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	21	theme	reduction	788:796	arg1	surface					748:754	the luminal surface	736:754	the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	736:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	22	from	residues	677:684	arg1	surface					748:754	the luminal surface	736:754	the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	736:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	7	23	theme	epithelial	1034:1043	arg1	cells					1045:1049	renal tubular epithelial cells	1020:1049	renal tubular epithelial cells	1020:1049	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	2	24	theme	epithelial	228:237	arg1	cells					239:243	epithelial cells	228:243	epithelial cells	228:243	In addition to myeloid cells, C5aR1 is expressed on epithelial cells.
29263309	7	25	from	expression	1006:1015	arg1	cells					1045:1049	renal tubular epithelial cells	1020:1049	renal tubular epithelial cells	1020:1049	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	3	26	theme	role	402:405	arg1	mechanisms					383:392	the underlying mechanisms	368:392	the underlying mechanisms of this role	368:405	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	3	27	theme	tubular	335:341	arg1	epithelium					343:352	renal tubular epithelium	329:352	renal tubular epithelium	329:352	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	7	28	from	part	1105:1108	arg1	dependent					1114:1122	dependent	1114:1122	dependent	1114:1122	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	6	29	theme	luminal	902:908	arg1	surface					910:916	the luminal surface	898:916	the luminal surface of renal tubular epithelium	898:944	Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium.
29263309	1	30	theme	N-linked	145:152	arg1	protein					167:173	an N-linked glycosylated protein	142:173	also an N-linked glycosylated protein	137:173	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	3	31	theme	epithelium	343:352	arg1	adhesion/colonization					304:324	bacterial adhesion/colonization	294:324	bacterial adhesion/colonization of renal tubular epithelium	294:352	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	4	32	theme	pharmacologic	511:523	arg1	inhibition					525:534	pharmacologic inhibition	511:534	pharmacologic inhibition of C5aR1	511:543	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	7	33	theme	renal	1020:1024	arg1	cells					1045:1049	renal tubular epithelial cells	1020:1049	renal tubular epithelial cells	1020:1049	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	7	34	theme	tubular	1026:1032	arg1	cells					1045:1049	renal tubular epithelial cells	1020:1049	renal tubular epithelial cells	1020:1049	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	1	35	theme	glycosylated	154:165	arg1	protein					167:173	an N-linked glycosylated protein	142:173	also an N-linked glycosylated protein	137:173	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	5	36	theme	luminal	740:746	arg1	surface					748:754	the luminal surface	736:754	the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	736:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	37	theme	α-mannosyl	666:675	arg1	residues					677:684	terminal α-mannosyl residues	657:684	terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	657:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	8	38	from	ligands	1387:1393	arg1	tubules					1404:1410	renal tubules	1398:1410	renal tubules	1398:1410	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	5	39	theme	renal	759:763	arg1	epithelium					773:782	renal tubular epithelium	759:782	renal tubular epithelium	759:782	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	3	40	theme	renal	329:333	arg1	epithelium					343:352	renal tubular epithelium	329:352	renal tubular epithelium	329:352	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	5	41	theme	residues	677:684	arg1	expression					643:652	reduced expression	635:652	reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	635:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	8	42	theme	acute	1258:1262	arg1	pyelonephritis					1264:1277	acute pyelonephritis	1258:1277	acute pyelonephritis	1258:1277	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	5	43	theme	tubular	765:771	arg1	epithelium					773:782	renal tubular epithelium	759:782	renal tubular epithelium	759:782	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	8	44	theme	unknown	1221:1227	arg1	role					1240:1243	a previously unknown pathogenic role	1208:1243	a previously unknown pathogenic role for C5aR1 in acute pyelonephritis	1208:1277	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	8	45	theme	renal	1398:1402	arg1	tubules					1404:1410	renal tubules	1398:1410	renal tubules	1398:1410	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	5	46	theme	UPEC	807:810	arg1	colonization					812:823	early UPEC colonization	801:823	early UPEC colonization	801:823	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	47	theme	epithelium	773:782	arg1	surface					748:754	the luminal surface	736:754	the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	736:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	3	48	theme	underlying	372:381	arg1	mechanisms					383:392	the underlying mechanisms	368:392	the underlying mechanisms of this role	368:405	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	4	49	theme	genetic	483:489	arg1	deletion					491:498	genetic deletion	483:498	genetic deletion	483:498	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	5	50	theme	coli	727:730	arg1	ligand					694:699	a ligand	692:699	Man; a ligand for type 1 fimbriae of E. coli	687:730	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	6	51	theme	renal	921:925	arg1	epithelium					935:944	renal tubular epithelium	921:944	renal tubular epithelium	921:944	Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium.
29263309	6	52	theme	epithelium	935:944	arg1	surface					910:916	the luminal surface	898:916	the luminal surface of renal tubular epithelium	898:944	Confocal microscopy demonstrated that UPEC bind to Man on the luminal surface of renal tubular epithelium.
29263309	5	53	from	epithelium	773:782	arg1	mice					834:837	these mice	828:837	these mice	828:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	2	54	dep	cells	199:203	arg1	addition					179:186	addition	179:186	addition	179:186	In addition to myeloid cells, C5aR1 is expressed on epithelial cells.
29263309	8	55	theme	pathogenic	1229:1238	arg1	role					1240:1243	a previously unknown pathogenic role	1208:1243	a previously unknown pathogenic role for C5aR1 in acute pyelonephritis	1208:1277	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	5	56	theme	reduced	635:641	arg1	expression					643:652	reduced expression	635:652	reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	635:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	7	57	theme	C5aR1-mediated	1143:1156	arg1	signaling					1172:1180	C5aR1-mediated intracellular signaling	1143:1180	C5aR1-mediated intracellular signaling	1143:1180	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	2	58	theme	myeloid	191:197	arg1	cells					199:203	myeloid cells	191:203	myeloid cells	191:203	In addition to myeloid cells, C5aR1 is expressed on epithelial cells.
29263309	8	59	theme	novel	1304:1308	arg1	mechanism					1310:1318	a potentially novel mechanism	1290:1318	a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion	1290:1438	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	4	60	with	mice	473:476	arg1	deletion					491:498	genetic deletion	483:498	genetic deletion	483:498	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	7	61	theme	C5a	977:979	arg1	stimulation					981:991	C5a stimulation	977:991	C5a stimulation	977:991	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	7	62	from	dependent	1114:1122	arg1	part					1105:1108	part	1105:1108	part	1105:1108	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	8	63	theme	carbohydrate	1374:1385	arg1	ligands					1387:1393	carbohydrate ligands	1374:1393	carbohydrate ligands on renal tubules	1374:1410	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	8	64	theme	ligands	1387:1393	arg1	upregulation					1358:1369	upregulation	1358:1369	upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion	1358:1438	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	8	65	theme	UPEC	1426:1429	arg1	adhesion					1431:1438	UPEC adhesion	1426:1438	UPEC adhesion	1426:1438	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	4	66	with	inoculation	563:573	arg1	UPEC					603:606	UPEC	603:606	UPEC	603:606	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	4	66	with	inoculation	563:573	arg1	coli					597:600	E. coli	594:600	uropathogenic E. coli (UPEC)	580:607	We show that acute kidney infection was significantly reduced in mice with genetic deletion or through pharmacologic inhibition of C5aR1 following bladder inoculation with uropathogenic E. coli (UPEC).
29263309	8	67	theme	C5a/C5aR1	1329:1337	arg1	signaling					1339:1347	C5a/C5aR1 signaling	1329:1347	C5a/C5aR1 signaling	1329:1347	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	5	68	theme	terminal	657:664	arg1	residues					677:684	terminal α-mannosyl residues	657:684	terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	657:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	3	69	from	role	277:280	arg1	adhesion/colonization					304:324	bacterial adhesion/colonization	294:324	bacterial adhesion/colonization of renal tubular epithelium	294:352	In this study, we examined the role of C5aR1 in bacterial adhesion/colonization of renal tubular epithelium and addressed the underlying mechanisms of this role.
29263309	7	70	theme	In	947:948	arg1	analyses					956:963	In vitro analyses	947:963	In vitro analyses	947:963	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	1	71	theme	protein-coupled	100:114	arg1	receptor					74:81	C5a receptor 1	70:83	C5a receptor 1 (C5aR1)	70:91	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	1	71	theme	protein-coupled	100:114	arg1	receptor					116:123	a G protein-coupled receptor	96:123	a G protein-coupled receptor for C5a and also an N-linked glycosylated protein	96:173	C5a receptor 1 (C5aR1) is a G protein-coupled receptor for C5a and also an N-linked glycosylated protein.
29263309	7	72	dep	In	947:948	arg1	vitro					950:954	vitro	950:954	vitro	950:954	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	5	73	theme	type	705:708	arg1	fimbriae					712:719	type 1 fimbriae	705:719	type 1 fimbriae	705:719	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	74	theme	colonization	812:823	arg1	epithelium					773:782	renal tubular epithelium	759:782	renal tubular epithelium	759:782	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	74	theme	colonization	812:823	arg1	reduction					788:796	reduction	788:796	reduction of early UPEC colonization in these mice	788:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	5	75	dep	Man	687:689	arg1	ligand					694:699	a ligand	692:699	Man; a ligand for type 1 fimbriae of E. coli	687:730	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	7	76	from	adhesion	1076:1083	arg1	cells					1045:1049	renal tubular epithelial cells	1020:1049	renal tubular epithelial cells	1020:1049	In vitro analyses showed that C5a stimulation enhances Man expression in renal tubular epithelial cells and subsequent bacterial adhesion, which, at least in part, is dependent on TNF-α driven by C5aR1-mediated intracellular signaling.
29263309	0	77	theme	acute	15:19	arg1	pyelonephritis					21:34	acute pyelonephritis	15:34	acute pyelonephritis induced by uropathogenic E. coli	15:67	C5aR1 promotes acute pyelonephritis induced by uropathogenic E. coli.
29263309	5	78	from	reduction	788:796	arg1	mice					834:837	these mice	828:837	these mice	828:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
29263309	8	79	from	role	1240:1243	arg1	pyelonephritis					1264:1277	acute pyelonephritis	1258:1277	acute pyelonephritis	1258:1277	Our findings demonstrate a previously unknown pathogenic role for C5aR1 in acute pyelonephritis, proposing a potentially novel mechanism by which C5a/C5aR1 signaling mediates upregulation of carbohydrate ligands on renal tubules to facilitate UPEC adhesion.
29263309	5	80	from	expression	643:652	arg1	surface					748:754	the luminal surface	736:754	the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice	736:837	This was associated with reduced expression of terminal α-mannosyl residues (Man; a ligand for type 1 fimbriae of E. coli) on the luminal surface of renal tubular epithelium and reduction of early UPEC colonization in these mice.
28232487	7	0	theme	cell	1183:1186	arg1	culture					1188:1194	cell culture	1183:1194	cell culture (SILAC)	1183:1202	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	7	0	theme	cell	1183:1186	arg1	SILAC					1197:1201	SILAC	1197:1201	SILAC	1197:1201	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	12	1	theme	remodeling	1846:1855	arg1	O-GlcNAcylation					1866:1880	remodeling cellular O-GlcNAcylation	1846:1880	remodeling cellular O-GlcNAcylation	1846:1880	Although the mechanism by which FAS sequesters OGA remains unknown, these data suggest that FAS fine-tunes the cell's response to stress and injury by remodeling cellular O-GlcNAcylation.
28232487	7	2	from	labeling	1156:1163	arg1	culture					1188:1194	cell culture	1183:1194	cell culture (SILAC)	1183:1202	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	7	2	from	labeling	1156:1163	arg1	SILAC					1197:1201	SILAC	1197:1201	SILAC	1197:1201	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	1	3	theme	nuclear	179:185	arg1	proteins					219:226	nuclear, cytoplasmic, and mitochondrial proteins	179:226	nuclear, cytoplasmic, and mitochondrial proteins	179:226	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	4	4	from	levels	688:693	arg1	cells					703:707	U2OS cells	698:707	U2OS cells	698:707	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	6	5	theme	OGA	960:962	arg1	activity					925:932	the local activity	915:932	the local activity	915:932	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	6	5	theme	OGA	960:962	arg1	targeting					947:955	substrate targeting	937:955	substrate targeting of OGA	937:962	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	7	6	used	utilized	1081:1088	arg2	we					1078:1079	we	1078:1079	we	1078:1079	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	7	7	theme	BioID	1090:1094	arg1	biotinylation					1106:1118	BioID proximity biotinylation	1090:1118	BioID proximity biotinylation	1090:1118	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	2	8	theme	cell	373:376	arg1	survival					378:385	cell survival	373:385	cell survival	373:385	Cellular stress, including oxidative stress, results in increased O-GlcNAcylation of numerous proteins, and this increase is thought to promote cell survival.
28232487	1	9	dep	modification	101:112	arg1	O-GlcNAc					146:153	O-GlcNAc	146:153	O-GlcNAc	146:153	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	1	9	dep	modification	101:112	arg1	β-N-acetylglucosamine					123:143	O-linked β-N-acetylglucosamine	114:143	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	70:154	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	7	10	theme	acids	1174:1178	arg1	labeling					1156:1163	stable isotopic labeling	1140:1163	stable isotopic labeling of amino acids in cell culture (SILAC)	1140:1202	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	7	11	with	combination	1123:1133	arg1	labeling					1156:1163	stable isotopic labeling	1140:1163	stable isotopic labeling of amino acids in cell culture (SILAC)	1140:1202	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	2	12	theme	proteins	323:330	arg1	O-GlcNAcylation					295:309	increased O-GlcNAcylation	285:309	increased O-GlcNAcylation of numerous proteins	285:330	Cellular stress, including oxidative stress, results in increased O-GlcNAcylation of numerous proteins, and this increase is thought to promote cell survival.
28232487	10	13	from	reduction	1534:1542	arg1	activity					1556:1563	specific activity	1547:1563	specific activity	1547:1563	The pool of OGA bound to FAS demonstrated a substantial (∼85%) reduction in specific activity, suggesting that FAS inhibits OGA.
28232487	12	14	theme	cellular	1857:1864	arg1	O-GlcNAcylation					1866:1880	remodeling cellular O-GlcNAcylation	1846:1880	remodeling cellular O-GlcNAcylation	1846:1880	Although the mechanism by which FAS sequesters OGA remains unknown, these data suggest that FAS fine-tunes the cell's response to stress and injury by remodeling cellular O-GlcNAcylation.
28232487	2	15	theme	numerous	314:321	arg1	proteins					323:330	numerous proteins	314:330	numerous proteins	314:330	Cellular stress, including oxidative stress, results in increased O-GlcNAcylation of numerous proteins, and this increase is thought to promote cell survival.
28232487	9	16	theme	cognate	1397:1403	arg1	protein					1412:1418	heat shock cognate 70-kDa protein	1386:1418	heat shock cognate 70-kDa protein	1386:1418	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	6	17	theme	substrate	937:945	arg1	targeting					947:955	substrate targeting	937:955	substrate targeting of OGA	937:962	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	4	18	contain	has	713:715	arg1	stress					654:659	oxidative stress	644:659	oxidative stress	644:659	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	4	18	contain	has	713:715	arg2	impact					724:729	little impact	717:729	little impact	717:729	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	7	19	theme	protein	1060:1066	arg1	partners					1068:1075	potential protein partners	1050:1075	potential protein partners	1050:1075	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	9	20	theme	70-kDa	1405:1410	arg1	protein					1412:1418	heat shock cognate 70-kDa protein	1386:1418	heat shock cognate 70-kDa protein	1386:1418	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	9	21	theme	heat	1386:1389	arg1	protein					1412:1418	heat shock cognate 70-kDa protein	1386:1418	heat shock cognate 70-kDa protein	1386:1418	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	1	22	theme	cytoplasmic	188:198	arg1	proteins					219:226	nuclear, cytoplasmic, and mitochondrial proteins	179:226	nuclear, cytoplasmic, and mitochondrial proteins	179:226	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	7	23	theme	amino	1168:1172	arg1	acids					1174:1178	amino acids	1168:1178	amino acids	1168:1178	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	10	24	dep	substantial	1515:1525	arg1	%					1531:1531	∼85%	1528:1531	∼85%	1528:1531	The pool of OGA bound to FAS demonstrated a substantial (∼85%) reduction in specific activity, suggesting that FAS inhibits OGA.
28232487	7	25	theme	proximity	1096:1104	arg1	biotinylation					1106:1118	BioID proximity biotinylation	1090:1118	BioID proximity biotinylation	1090:1118	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	1	26	theme	dynamic	74:80	arg1	modification					101:112	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	70:154	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	70:154	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	4	27	theme	oxidative	644:652	arg1	stress					654:659	oxidative stress	644:659	oxidative stress	644:659	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	0	28	theme	acid	6:9	arg1	synthase					11:18	Fatty acid synthase	0:18	Fatty acid synthase	0:18	Fatty acid synthase inhibits the O-GlcNAcase during oxidative stress.
28232487	6	29	theme	seeming	843:849	arg1	paradox					851:857	this seeming paradox	838:857	this seeming paradox	838:857	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	1	30	theme	post-translational	82:99	arg1	modification					101:112	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	70:154	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	70:154	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	7	31	theme	isotopic	1147:1154	arg1	labeling					1156:1163	stable isotopic labeling	1140:1163	stable isotopic labeling of amino acids in cell culture (SILAC)	1140:1202	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	6	32	theme	O-GlcNAc	1028:1035	arg1	elevations					1014:1023	the observed stress-induced elevations	986:1023	the observed stress-induced elevations of O-GlcNAc	986:1035	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	0	33	theme	Fatty	0:4	arg1	synthase					11:18	Fatty acid synthase	0:18	Fatty acid synthase	0:18	Fatty acid synthase inhibits the O-GlcNAcase during oxidative stress.
28232487	7	34	theme	potential	1050:1058	arg1	partners					1068:1075	potential protein partners	1050:1075	potential protein partners	1050:1075	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	4	35	theme	little	717:722	arg1	impact					724:729	little impact	717:729	little impact	717:729	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	11	36	with	Consistent	1600:1609	arg1	observation					1621:1631	this observation	1616:1631	this observation	1616:1631	Consistent with this observation, FAS overexpression augmented stress-induced O-GlcNAcylation.
28232487	1	37	theme	mitochondrial	205:217	arg1	proteins					219:226	nuclear, cytoplasmic, and mitochondrial proteins	179:226	nuclear, cytoplasmic, and mitochondrial proteins	179:226	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	9	38	with	associations	1323:1334	arg1	FAS					1369:1371	FAS	1369:1371	FAS	1369:1371	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	9	38	with	associations	1323:1334	arg1	filamin-A					1375:1383	filamin-A	1375:1383	filamin-A	1375:1383	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	9	38	with	associations	1323:1334	arg1	synthase					1359:1366	fatty acid synthase	1348:1366	fatty acid synthase (FAS)	1348:1372	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	9	38	with	associations	1323:1334	arg1	protein					1412:1418	heat shock cognate 70-kDa protein	1386:1418	heat shock cognate 70-kDa protein	1386:1418	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	9	38	with	associations	1323:1334	arg1	OGT					1425:1427	OGT	1425:1427	OGT	1425:1427	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	1	39	theme	O-linked	114:121	arg1	O-GlcNAc					146:153	O-GlcNAc	146:153	O-GlcNAc	146:153	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	1	39	theme	O-linked	114:121	arg1	β-N-acetylglucosamine					123:143	O-linked β-N-acetylglucosamine	114:143	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	70:154	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	1	40	theme	proteins	219:226	arg1	thousands					166:174	thousands	166:174	thousands of nuclear, cytoplasmic, and mitochondrial proteins	166:226	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	7	41	theme	stable	1140:1145	arg1	labeling					1156:1163	stable isotopic labeling	1140:1163	stable isotopic labeling of amino acids in cell culture (SILAC)	1140:1202	To identify potential protein partners, we utilized BioID proximity biotinylation in combination with stable isotopic labeling of amino acids in cell culture (SILAC).
28232487	6	42	theme	local	919:923	arg1	activity					925:932	the local activity	915:932	the local activity	915:932	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	3	43	theme	oxidative	547:555	arg1	stress					557:562	oxidative stress	547:562	oxidative stress	547:562	The mechanisms by which the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA), the enzymes that add and remove O-GlcNAc, respectively, are regulated during oxidative stress to alter O-GlcNAcylation are not fully characterized.
28232487	6	44	theme	stress-induced	999:1012	arg1	elevations					1014:1023	the observed stress-induced elevations	986:1023	the observed stress-induced elevations of O-GlcNAc	986:1035	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	10	45	theme	specific	1547:1554	arg1	activity					1556:1563	specific activity	1547:1563	specific activity	1547:1563	The pool of OGA bound to FAS demonstrated a substantial (∼85%) reduction in specific activity, suggesting that FAS inhibits OGA.
28232487	8	46	theme	partners	1247:1254	arg1	many					1257:1260	many	1257:1260	many	1257:1260	This analysis revealed 90 OGA-interacting partners, many of which exhibited increased binding to OGA upon stress.
28232487	8	46	theme	partners	1247:1254	arg1	partners					1247:1254	90 OGA-interacting partners	1228:1254	90 OGA-interacting partners	1228:1254	This analysis revealed 90 OGA-interacting partners, many of which exhibited increased binding to OGA upon stress.
28232487	9	47	theme	shock	1391:1395	arg1	protein					1412:1418	heat shock cognate 70-kDa protein	1386:1418	heat shock cognate 70-kDa protein	1386:1418	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	6	48	theme	observed	990:997	arg1	elevations					1014:1023	the observed stress-induced elevations	986:1023	the observed stress-induced elevations of O-GlcNAc	986:1035	We hypothesized that this seeming paradox could be explained by proteins that bind to and control the local activity or substrate targeting of OGA, thereby resulting in the observed stress-induced elevations of O-GlcNAc.
28232487	2	49	theme	oxidative	256:264	arg1	stress					266:271	oxidative stress	256:271	oxidative stress	256:271	Cellular stress, including oxidative stress, results in increased O-GlcNAcylation of numerous proteins, and this increase is thought to promote cell survival.
28232487	8	50	theme	OGA-interacting	1231:1245	arg1	partners					1247:1254	90 OGA-interacting partners	1228:1254	90 OGA-interacting partners	1228:1254	This analysis revealed 90 OGA-interacting partners, many of which exhibited increased binding to OGA upon stress.
28232487	3	51	theme	O-GlcNAc	416:423	arg1	transferase					425:435	the O-GlcNAc transferase	412:435	the O-GlcNAc transferase (OGT)	412:441	The mechanisms by which the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA), the enzymes that add and remove O-GlcNAc, respectively, are regulated during oxidative stress to alter O-GlcNAcylation are not fully characterized.
28232487	3	51	theme	O-GlcNAc	416:423	arg1	OGT					438:440	OGT	438:440	OGT	438:440	The mechanisms by which the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA), the enzymes that add and remove O-GlcNAc, respectively, are regulated during oxidative stress to alter O-GlcNAcylation are not fully characterized.
28232487	10	52	theme	OGA	1483:1485	arg1	pool					1475:1478	The pool	1471:1478	The pool of OGA bound to FAS	1471:1498	The pool of OGA bound to FAS demonstrated a substantial (∼85%) reduction in specific activity, suggesting that FAS inhibits OGA.
28232487	11	53	theme	stress-induced	1663:1676	arg1	O-GlcNAcylation					1678:1692	stress-induced O-GlcNAcylation	1663:1692	stress-induced O-GlcNAcylation	1663:1692	Consistent with this observation, FAS overexpression augmented stress-induced O-GlcNAcylation.
28232487	4	54	theme	U2OS	698:701	arg1	cells					703:707	U2OS cells	698:707	U2OS cells	698:707	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	9	55	theme	OGA	1339:1341	arg1	associations					1323:1334	The associations	1319:1334	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT	1319:1427	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	2	56	theme	Cellular	229:236	arg1	stress					238:243	Cellular stress	229:243	Cellular stress	229:243	Cellular stress, including oxidative stress, results in increased O-GlcNAcylation of numerous proteins, and this increase is thought to promote cell survival.
28232487	2	57	theme	increased	285:293	arg1	O-GlcNAcylation					295:309	increased O-GlcNAcylation	285:309	increased O-GlcNAcylation of numerous proteins	285:330	Cellular stress, including oxidative stress, results in increased O-GlcNAcylation of numerous proteins, and this increase is thought to promote cell survival.
28232487	4	58	theme	OGT	750:752	arg1	activity					738:745	the activity	734:745	the activity of OGT	734:752	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	8	59	theme	increased	1281:1289	arg1	binding					1291:1297	increased binding	1281:1297	increased binding to OGA	1281:1304	This analysis revealed 90 OGA-interacting partners, many of which exhibited increased binding to OGA upon stress.
28232487	9	60	theme	fatty	1348:1352	arg1	FAS					1369:1371	FAS	1369:1371	FAS	1369:1371	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	9	60	theme	fatty	1348:1352	arg1	synthase					1359:1366	fatty acid synthase	1348:1366	fatty acid synthase (FAS)	1348:1372	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	1	61	link	O-linked	114:121	arg1	O-GlcNAc					146:153	O-GlcNAc	146:153	O-GlcNAc	146:153	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	1	61	link	O-linked	114:121	arg1	β-N-acetylglucosamine					123:143	O-linked β-N-acetylglucosamine	114:143	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc)	70:154	The dynamic post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc) regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins.
28232487	11	62	theme	FAS	1634:1636	arg1	overexpression					1638:1651	FAS overexpression	1634:1651	FAS overexpression	1634:1651	Consistent with this observation, FAS overexpression augmented stress-induced O-GlcNAcylation.
28232487	5	63	theme	OGA	799:801	arg1	activity					787:794	activity	787:794	activity	787:794	In contrast, the expression and activity of OGA are enhanced.
28232487	5	63	theme	OGA	799:801	arg1	expression					772:781	expression	772:781	expression	772:781	In contrast, the expression and activity of OGA are enhanced.
28232487	4	64	theme	O-GlcNAc	679:686	arg1	levels					688:693	elevated O-GlcNAc levels	670:693	elevated O-GlcNAc levels in U2OS cells	670:707	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
28232487	9	65	theme	acid	1354:1357	arg1	FAS					1369:1371	FAS	1369:1371	FAS	1369:1371	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	9	65	theme	acid	1354:1357	arg1	synthase					1359:1366	fatty acid synthase	1348:1366	fatty acid synthase (FAS)	1348:1372	The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70-kDa protein, and OGT were confirmed by co-immunoprecipitation.
28232487	0	66	theme	oxidative	52:60	arg1	stress					62:67	oxidative stress	52:67	oxidative stress	52:67	Fatty acid synthase inhibits the O-GlcNAcase during oxidative stress.
28232487	10	67	theme	substantial	1515:1525	arg1	reduction					1534:1542	a substantial (∼85%) reduction	1513:1542	a substantial (∼85%) reduction in specific activity	1513:1563	The pool of OGA bound to FAS demonstrated a substantial (∼85%) reduction in specific activity, suggesting that FAS inhibits OGA.
28232487	4	68	theme	elevated	670:677	arg1	levels					688:693	elevated O-GlcNAc levels	670:693	elevated O-GlcNAc levels in U2OS cells	670:707	Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells but has little impact on the activity of OGT.
27986835	7	0	theme	Campylobacter	1502:1514	arg1	jejuni					1516:1521	Campylobacter jejuni	1502:1521	Campylobacter jejuni involving GDP-sugar intermediates	1502:1555	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	4	1	theme	pseudaminic	592:602	arg1	acid					604:607	pseudaminic acid	592:607	pseudaminic acid (Pse)	592:613	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	1	theme	pseudaminic	592:602	arg1	Pse					610:612	Pse	610:612	Pse	610:612	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	1	2	theme	Gram-negative	203:215	arg1	pathogen					229:236	an anaerobic, Gram-negative periodontal pathogen	189:236	pathogen	229:236	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	1	2	theme	Gram-negative	203:215	arg1	forsythia					176:184	Tannerella forsythia	165:184	Tannerella forsythia	165:184	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	9	3	from	involvement	1853:1863	arg1	interactions					1882:1893	host-pathogen interactions	1868:1893	host-pathogen interactions	1868:1893	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	9	3	from	involvement	1853:1863	arg1	survival					1903:1910	host survival	1898:1910	host survival	1898:1910	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	6	4	theme	pathways	1174:1181	arg1	enzymes					1153:1159	enzymes	1153:1159	enzymes of both NulO pathways	1153:1181	We have expressed, purified and characterized enzymes of both NulO pathways to confirm these genes' functions.
27986835	2	5	theme	host	351:354	arg1	response					363:370	the host immune response	347:370	the host immune response	347:370	A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response.
27986835	9	6	theme	wild-type	1726:1734	arg1	strains					1736:1742	the wild-type strains	1722:1742	the wild-type strains	1722:1742	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	7	7	theme	Helicobacter	1409:1420	arg1	pylori					1422:1427	Helicobacter pylori	1409:1427	Helicobacter pylori	1409:1427	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	4	8	theme	strain	627:632	arg1	ATCC					634:637	the type strain ATCC 43037	618:643	the type strain ATCC 43037	618:643	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	0	9	theme	biological	140:149	arg1	implications					151:162	biological implications	140:162	biological implications	140:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	5	10	theme	C5,7	1085:1088	arg1	moieties					1097:1104	unknown C5,7 N-acyl moieties	1077:1104	unknown C5,7 N-acyl moieties	1077:1104	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	7	11	theme	UDP-sugar	1380:1388	arg1	route					1390:1394	the UDP-sugar route	1376:1394	the UDP-sugar route described in Helicobacter pylori	1376:1427	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	2	12	theme	surface	304:310	arg1	proteins					312:319	the bacterium's cell surface proteins	283:319	the bacterium's cell surface proteins	283:319	A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response.
27986835	1	13	theme	Tannerella	165:174	arg1	pathogen					229:236	an anaerobic, Gram-negative periodontal pathogen	189:236	pathogen	229:236	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	1	13	theme	Tannerella	165:174	arg1	forsythia					176:184	Tannerella forsythia	165:184	Tannerella forsythia	165:184	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	9	14	theme	biofilm	1789:1795	arg1	formation					1797:1805	significantly reduced biofilm formation	1767:1805	significantly reduced biofilm formation	1767:1805	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	0	15	theme	pathway	92:98	arg1	characterization					100:115	biosynthetic pathway characterization	79:115	biosynthetic pathway characterization	79:115	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	15	theme	pathway	92:98	arg1	acids					72:76	different cell-surface nonulosonic acids	37:76	different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications	37:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	1	16	theme	anaerobic	192:200	arg1	pathogen					229:236	an anaerobic, Gram-negative periodontal pathogen	189:236	pathogen	229:236	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	1	16	theme	anaerobic	192:200	arg1	forsythia					176:184	Tannerella forsythia	165:184	Tannerella forsythia	165:184	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	4	17	theme	T.	528:529	arg1	genomes					541:547	T. forsythia genomes	528:547	T. forsythia genomes	528:547	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	5	18	from	NulO	765:768	arg1	ATCC					773:776	ATCC 43037	773:782	ATCC 43037	773:782	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	10	19	theme	biological	1962:1971	arg1	roles					1973:1977	possible biological roles	1953:1977	possible biological roles of bacterial NulOs	1953:1996	This study contributes to understanding possible biological roles of bacterial NulOs.
27986835	4	20	theme	legionaminic	713:724	arg1	acid					726:729	legionaminic acid	713:729	legionaminic acid (Leg)	713:735	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	20	theme	legionaminic	713:724	arg1	Leg					732:734	Leg	732:734	Leg	732:734	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	5	21	with	derivative	1061:1070	arg1	moieties					1097:1104	unknown C5,7 N-acyl moieties	1077:1104	unknown C5,7 N-acyl moieties	1077:1104	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	0	22	theme	Tannerella	0:9	arg1	strains					21:27	Tannerella forsythia strains	0:27	Tannerella forsythia strains	0:27	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	5	23	theme	strain	936:941	arg1	UB4					943:945	strain UB4	936:945	strain UB4	936:945	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	4	24	from	locus	565:569	arg1	ATCC					634:637	the type strain ATCC 43037	618:643	the type strain ATCC 43037	618:643	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	8	25	theme	biosynthesis	1587:1598	arg1	enzymes					1600:1606	the NulO biosynthesis enzymes	1578:1606	the NulO biosynthesis enzymes	1578:1606	To demonstrate that the NulO biosynthesis enzymes are functional in vivo, we created knockout mutants resulting in glycans lacking the respective NulO.
27986835	2	26	link	O-linked	248:255	arg1	oligosaccharide					257:271	A unique O-linked oligosaccharide	239:271	A unique O-linked oligosaccharide	239:271	A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response.
27986835	3	27	theme	terminal	466:473	arg1	position					475:482	the terminal position	462:482	the terminal position of this glycan	462:497	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	0	28	theme	different	37:45	arg1	characterization					100:115	biosynthetic pathway characterization	79:115	biosynthetic pathway characterization	79:115	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	28	theme	different	37:45	arg1	insight					127:133	first insight	121:133	first insight into biological implications	121:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	28	theme	different	37:45	arg1	acids					72:76	different cell-surface nonulosonic acids	37:76	different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications	37:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	5	29	theme	Leg	1011:1013	arg1	derivative					1061:1070	a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative	981:1070	a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties	981:1104	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	3	30	theme	nonulosonic	427:437	arg1	acid					439:442	the nonulosonic acid	423:442	the nonulosonic acid (NulO) present at the terminal position of this glycan	423:497	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	3	30	theme	nonulosonic	427:437	arg1	NulO					445:448	NulO	445:448	NulO	445:448	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	4	31	theme	genomes	541:547	arg1	analysis					516:523	A bioinformatic analysis	500:523	A bioinformatic analysis of T. forsythia genomes	500:547	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	3	32	from	position	475:482	arg1	present					451:457	present	451:457	present	451:457	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	0	33	theme	nonulosonic	60:70	arg1	characterization					100:115	biosynthetic pathway characterization	79:115	biosynthetic pathway characterization	79:115	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	33	theme	nonulosonic	60:70	arg1	insight					127:133	first insight	121:133	first insight into biological implications	121:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	33	theme	nonulosonic	60:70	arg1	acids					72:76	different cell-surface nonulosonic acids	37:76	different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications	37:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	7	34	theme	GDP-sugar	1533:1541	arg1	intermediates					1543:1555	GDP-sugar intermediates	1533:1555	GDP-sugar intermediates	1533:1555	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	5	35	theme	3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO	1016:1058	arg1	derivative					1061:1070	a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative	981:1070	a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties	981:1104	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	10	36	theme	possible	1953:1960	arg1	roles					1973:1977	possible biological roles	1953:1977	possible biological roles of bacterial NulOs	1953:1996	This study contributes to understanding possible biological roles of bacterial NulOs.
27986835	3	37	theme	glycan	492:497	arg1	position					475:482	the terminal position	462:482	the terminal position of this glycan	462:497	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	5	38	theme	350-Da	983:988	arg1	derivative					1061:1070	a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative	981:1070	a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties	981:1104	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	7	39	theme	NMR	1281:1283	arg1	spectroscopy					1285:1296	NMR spectroscopy	1281:1296	NMR spectroscopy	1281:1296	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	8	40	theme	respective	1693:1702	arg1	NulO					1704:1707	the respective NulO	1689:1707	the respective NulO	1689:1707	To demonstrate that the NulO biosynthesis enzymes are functional in vivo, we created knockout mutants resulting in glycans lacking the respective NulO.
27986835	9	41	theme	host	1898:1901	arg1	survival					1903:1910	host survival	1898:1910	host survival	1898:1910	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	10	42	theme	bacterial	1982:1990	arg1	NulOs					1992:1996	bacterial NulOs	1982:1996	bacterial NulOs	1982:1996	This study contributes to understanding possible biological roles of bacterial NulOs.
27986835	7	43	theme	Leg	1482:1484	arg1	biosynthesis					1486:1497	Leg biosynthesis	1482:1497	Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates	1482:1555	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	7	44	theme	strain	1451:1456	arg1	92A2					1462:1465	strain FDC 92A2	1451:1465	strain FDC 92A2	1451:1465	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	4	45	theme	acid	604:607	arg1	synthesis					579:587	the synthesis	575:587	the synthesis of pseudaminic acid (Pse)	575:613	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	7	46	theme	FDC	1458:1460	arg1	92A2					1462:1465	strain FDC 92A2	1451:1465	strain FDC 92A2	1451:1465	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	2	47	theme	immune	356:361	arg1	response					363:370	the host immune response	347:370	the host immune response	347:370	A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response.
27986835	1	48	theme	periodontal	217:227	arg1	pathogen					229:236	an anaerobic, Gram-negative periodontal pathogen	189:236	pathogen	229:236	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	1	48	theme	periodontal	217:227	arg1	forsythia					176:184	Tannerella forsythia	165:184	Tannerella forsythia	165:184	Tannerella forsythia is an anaerobic, Gram-negative periodontal pathogen.
27986835	3	49	attach	present	451:457	arg2	NulO					445:448	NulO	445:448	NulO	445:448	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	3	49	attach	present	451:457	arg1	position					475:482	the terminal position	462:482	the terminal position of this glycan	462:497	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	3	49	attach	present	451:457	arg2	acid					439:442	the nonulosonic acid	423:442	the nonulosonic acid (NulO) present at the terminal position of this glycan	423:497	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	6	50	theme	NulO	1169:1172	arg1	pathways					1174:1181	both NulO pathways	1164:1181	both NulO pathways	1164:1181	We have expressed, purified and characterized enzymes of both NulO pathways to confirm these genes' functions.
27986835	4	51	theme	FDC	659:661	arg1	strains					651:657	strains	651:657	strains FDC 92A2 and UB4	651:674	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	51	theme	FDC	659:661	arg1	92A2					663:666	FDC 92A2	659:666	FDC 92A2	659:666	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	52	theme	type	622:625	arg1	ATCC					634:637	the type strain ATCC 43037	618:643	the type strain ATCC 43037	618:643	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	5	53	theme	N-acyl	1090:1095	arg1	moieties					1097:1104	unknown C5,7 N-acyl moieties	1077:1104	unknown C5,7 N-acyl moieties	1077:1104	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	7	54	from	biosynthesis	1486:1497	arg1	jejuni					1516:1521	Campylobacter jejuni	1502:1521	Campylobacter jejuni involving GDP-sugar intermediates	1502:1555	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	5	55	dep	350-Da	983:988	arg1	N-glycolyl					1000:1009	N-glycolyl	1000:1009	N-glycolyl	1000:1009	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	2	56	theme	unique	241:246	arg1	oligosaccharide					257:271	A unique O-linked oligosaccharide	239:271	A unique O-linked oligosaccharide	239:271	A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response.
27986835	5	57	theme	glycan	917:922	arg1	analysis					924:931	glycan analysis	917:931	glycan analysis of strain UB4 performed in this study	917:969	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	9	58	theme	reduced	1781:1787	arg1	formation					1797:1805	significantly reduced biofilm formation	1767:1805	significantly reduced biofilm formation	1767:1805	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	0	59	theme	biosynthetic	79:90	arg1	characterization					100:115	biosynthetic pathway characterization	79:115	biosynthetic pathway characterization	79:115	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	59	theme	biosynthetic	79:90	arg1	acids					72:76	different cell-surface nonulosonic acids	37:76	different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications	37:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	5	60	theme	unknown	1077:1083	arg1	moieties					1097:1104	unknown C5,7 N-acyl moieties	1077:1104	unknown C5,7 N-acyl moieties	1077:1104	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	2	61	theme	cell	299:302	arg1	proteins					312:319	the bacterium's cell surface proteins	283:319	the bacterium's cell surface proteins	283:319	A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response.
27986835	5	62	theme	Pse	827:829	arg1	5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO					843:913	5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO	843:913	5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO	843:913	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	5	62	theme	Pse	827:829	arg1	derivative					831:840	a Pse derivative	825:840	a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO)	825:914	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	5	62	theme	Pse	827:829	arg1	contrast					749:756	contrast	749:756	contrast	749:756	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	7	63	theme	capillary	1224:1232	arg1	electrophoresis					1234:1248	capillary electrophoresis	1224:1248	capillary electrophoresis (CE)	1224:1253	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	7	63	theme	capillary	1224:1232	arg1	CE					1251:1252	CE	1251:1252	CE	1251:1252	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	7	64	from	pathway	1440:1446	arg1	92A2					1462:1465	strain FDC 92A2	1451:1465	strain FDC 92A2	1451:1465	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	9	65	theme	mucin-coated	1810:1821	arg1	surfaces					1823:1830	mucin-coated surfaces	1810:1830	mucin-coated surfaces	1810:1830	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	4	66	theme	forsythia	531:539	arg1	genomes					541:547	T. forsythia genomes	528:547	T. forsythia genomes	528:547	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	0	67	theme	first	121:125	arg1	insight					127:133	first insight	121:133	first insight into biological implications	121:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	67	theme	first	121:125	arg1	acids					72:76	different cell-surface nonulosonic acids	37:76	different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications	37:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	4	68	theme	bioinformatic	502:514	arg1	analysis					516:523	A bioinformatic analysis	500:523	A bioinformatic analysis of T. forsythia genomes	500:547	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	0	69	theme	forsythia	11:19	arg1	strains					21:27	Tannerella forsythia strains	0:27	Tannerella forsythia strains	0:27	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	7	70	theme	Pse	1325:1327	arg1	biosynthesis					1329:1340	Pse biosynthesis	1325:1340	Pse biosynthesis in ATCC 43037	1325:1354	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	9	71	theme	involvement	1853:1863	arg1	suggestive					1833:1842	suggestive	1833:1842	suggestive	1833:1842	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	8	72	theme	NulO	1582:1585	arg1	enzymes					1600:1606	the NulO biosynthesis enzymes	1578:1606	the NulO biosynthesis enzymes	1578:1606	To demonstrate that the NulO biosynthesis enzymes are functional in vivo, we created knockout mutants resulting in glycans lacking the respective NulO.
27986835	3	73	theme	present	451:457	arg1	acid					439:442	the nonulosonic acid	423:442	the nonulosonic acid (NulO) present at the terminal position of this glycan	423:497	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	3	73	theme	present	451:457	arg1	NulO					445:448	NulO	445:448	NulO	445:448	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	5	74	theme	UB4	943:945	arg1	analysis					924:931	glycan analysis	917:931	glycan analysis of strain UB4 performed in this study	917:969	In contrast to the NulO in ATCC 43037, which has been previously identified as a Pse derivative (5-N-acetimidoyl-7-N-glyceroyl-3,5,7,9-tetradeoxy-l-glycero-l-manno-NulO), glycan analysis of strain UB4 performed in this study indicated a 350-Da, possibly N-glycolyl Leg (3,5,7,9-tetradeoxy-d-glycero-d-galacto-NulO) derivative with unknown C5,7 N-acyl moieties.
27986835	9	75	theme	host-pathogen	1868:1880	arg1	interactions					1882:1893	host-pathogen interactions	1868:1893	host-pathogen interactions	1868:1893	Compared to the wild-type strains, the mutants exhibited significantly reduced biofilm formation on mucin-coated surfaces, suggestive of their involvement in host-pathogen interactions or host survival.
27986835	4	76	theme	acid	726:729	arg1	synthesis					700:708	the synthesis	696:708	the synthesis of legionaminic acid (Leg)	696:735	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	0	77	theme	cell-surface	47:58	arg1	characterization					100:115	biosynthetic pathway characterization	79:115	biosynthetic pathway characterization	79:115	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	77	theme	cell-surface	47:58	arg1	insight					127:133	first insight	121:133	first insight into biological implications	121:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	77	theme	cell-surface	47:58	arg1	acids					72:76	different cell-surface nonulosonic acids	37:76	different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications	37:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	78	dep	acids	72:76	arg1	characterization					100:115	biosynthetic pathway characterization	79:115	biosynthetic pathway characterization	79:115	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	78	dep	acids	72:76	arg1	insight					127:133	first insight	121:133	first insight into biological implications	121:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	0	78	dep	acids	72:76	arg1	acids					72:76	different cell-surface nonulosonic acids	37:76	different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications	37:162	Tannerella forsythia strains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications.
27986835	3	79	theme	acid	439:442	arg1	biosynthesis					407:418	the biosynthesis	403:418	the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan	403:497	In our study, we investigated the biosynthesis of the nonulosonic acid (NulO) present at the terminal position of this glycan.
27986835	4	80	theme	gene	560:563	arg1	locus					565:569	a gene locus	558:569	a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037	558:643	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	81	contain	possess	676:682	arg1	strains					651:657	strains	651:657	strains FDC 92A2 and UB4	651:674	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	81	contain	possess	676:682	arg1	92A2					663:666	FDC 92A2	659:666	FDC 92A2	659:666	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	81	contain	possess	676:682	arg2	locus					686:690	a locus	684:690	a locus for the synthesis of legionaminic acid (Leg)	684:735	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	81	contain	possess	676:682	arg1	UB4					672:674	UB4	672:674	UB4	672:674	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	2	82	theme	O-linked	248:255	arg1	oligosaccharide					257:271	A unique O-linked oligosaccharide	239:271	A unique O-linked oligosaccharide	239:271	A unique O-linked oligosaccharide decorates the bacterium's cell surface proteins and was shown to modulate the host immune response.
27986835	4	83	dep	strains	651:657	arg1	strains					651:657	strains	651:657	strains FDC 92A2 and UB4	651:674	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	83	dep	strains	651:657	arg1	UB4					672:674	UB4	672:674	UB4	672:674	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	4	83	dep	strains	651:657	arg1	92A2					663:666	FDC 92A2	659:666	FDC 92A2	659:666	A bioinformatic analysis of T. forsythia genomes revealed a gene locus for the synthesis of pseudaminic acid (Pse) in the type strain ATCC 43037 while strains FDC 92A2 and UB4 possess a locus for the synthesis of legionaminic acid (Leg) instead.
27986835	7	84	from	biosynthesis	1329:1340	arg1	ATCC					1345:1348	ATCC 43037	1345:1354	ATCC 43037	1345:1354	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	7	85	theme	CE-mass	1256:1262	arg1	spectrometry					1264:1275	CE-mass spectrometry	1256:1275	CE-mass spectrometry	1256:1275	Using capillary electrophoresis (CE), CE-mass spectrometry and NMR spectroscopy, our studies revealed that Pse biosynthesis in ATCC 43037 essentially follows the UDP-sugar route described in Helicobacter pylori, while the pathway in strain FDC 92A2 corresponds to Leg biosynthesis in Campylobacter jejuni involving GDP-sugar intermediates.
27986835	8	86	theme	knockout	1643:1650	arg1	mutants					1652:1658	knockout mutants	1643:1658	knockout mutants resulting in glycans lacking the respective NulO	1643:1707	To demonstrate that the NulO biosynthesis enzymes are functional in vivo, we created knockout mutants resulting in glycans lacking the respective NulO.
27986835	10	87	theme	NulOs	1992:1996	arg1	roles					1973:1977	possible biological roles	1953:1977	possible biological roles of bacterial NulOs	1953:1996	This study contributes to understanding possible biological roles of bacterial NulOs.
31831633	12	0	theme	Spotlight	1947:1955	arg1	pathogenesis					1891:1902	the pathogenesis	1887:1902	the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160	1887:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	4	1	theme	increased	615:623	arg1	levels					636:641	increased expression levels	615:641	increased expression levels of inflammatory macrophage-associated cytokines	615:689	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	4	2	from	profiling	541:549	arg1	tissues					600:606	inflamed and malignant colon tissues	571:606	inflamed and malignant colon tissues	571:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	1	3	contain	have	184:187	arg1	Patients					151:158	Patients	151:158	Patients with ulcerative colitis	151:182	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	1	3	contain	have	184:187	arg2	risk					202:205	an increased risk	189:205	an increased risk of developing colitis-associated colon cancer (CACC)	189:258	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	2	4	theme	MUC1	305:308	arg1	glycosylation					272:284	glycosylation	272:284	glycosylation of the oncoprotein MUC1	272:308	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	8	5	theme	M2-like	1270:1276	arg1	macrophages					1278:1288	M2-like macrophages	1270:1288	M2-like macrophages	1270:1288	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	12	6	theme	colitis	1918:1924	arg1	pathogenesis					1891:1902	the pathogenesis	1887:1902	the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160	1887:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	11	7	theme	IL13	1702:1705	arg1	therapy					1732:1738	a possible therapy	1721:1738	a possible therapy	1721:1738	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	11	7	theme	IL13	1702:1705	arg1	inhibition					1707:1716	IL13 inhibition	1702:1716	IL13 inhibition	1702:1716	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	1	8	theme	increased	192:200	arg1	risk					202:205	an increased risk	189:205	an increased risk of developing colitis-associated colon cancer (CACC)	189:258	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	8	9	theme	MUC1-sTn	1347:1354	arg1	glycoform					1356:1364	the altered MUC1-sTn glycoform	1335:1364	the altered MUC1-sTn glycoform on colon cells	1335:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	6	10	from	enzymes	931:937	arg1	cells					955:959	colon cancer cells	942:959	colon cancer cells	942:959	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	2	11	theme	chronic	328:334	arg1	inflammation					336:347	chronic inflammation	328:347	chronic inflammation	328:347	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	0	12	theme	Colon	137:141	arg1	Cancer					143:148	Colitis-Associated Colon Cancer	118:148	Colitis-Associated Colon Cancer	118:148	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	1	13	theme	colitis-associated	221:238	arg1	CACC					254:257	CACC	254:257	CACC	254:257	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	1	13	theme	colitis-associated	221:238	arg1	cancer					246:251	colitis-associated colon cancer	221:251	colitis-associated colon cancer (CACC)	221:258	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	0	14	from	Expression	81:90	arg1	Colitis					106:112	Ulcerative Colitis	95:112	Ulcerative Colitis	95:112	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	0	14	from	Expression	81:90	arg1	Cancer					143:148	Colitis-Associated Colon Cancer	118:148	Colitis-Associated Colon Cancer	118:148	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	8	15	theme	ST6GALNAC1	1320:1329	arg1	number					1260:1265	the elevated number	1247:1265	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	8	15	theme	ST6GALNAC1	1320:1329	arg1	expression					1306:1315	high expression	1301:1315	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	7	16	theme	tumor-associated	1132:1147	arg1	O-glycans					1165:1173	tumor-associated sialyl-Tn (sTn) O-glycans	1132:1173	tumor-associated sialyl-Tn (sTn) O-glycans	1132:1173	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	8	17	gly	glycoform	1356:1364	arg2	cells					1375:1379	colon cells	1369:1379	colon cells	1369:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	8	17	gly	glycoform	1356:1364	arg1	MUC1-sTn					1347:1354	the altered MUC1-sTn glycoform	1335:1364	the altered MUC1-sTn glycoform on colon cells	1335:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	7	18	theme	GalNAc	1088:1093	arg1	residues					1095:1102	O-linked GalNAc residues	1079:1102	O-linked GalNAc residues	1079:1102	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	12	19	theme	malignant	1851:1859	arg1	colon					1861:1865	the inflamed and malignant colon	1834:1865	the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160	1834:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	11	20	theme	computational	1629:1641	arg1	model					1643:1647	A computational model	1627:1647	A computational model of signaling pathways	1627:1669	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	5	21	theme	cytokines	774:782	arg1	involvement					737:747	the involvement	733:747	the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms	733:827	We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms.
31831633	8	22	from	cells	1375:1379	arg1	number					1260:1265	the elevated number	1247:1265	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	8	22	from	cells	1375:1379	arg1	expression					1306:1315	high expression	1301:1315	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	7	23	theme	sialic	1064:1069	arg1	acid					1071:1074	sialic acid	1064:1074	sialic acid	1064:1074	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	1	24	theme	ulcerative	165:174	arg1	colitis					176:182	ulcerative colitis	165:182	ulcerative colitis	165:182	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	4	25	theme	Gene	525:528	arg1	profiling					541:549	Gene expression profiling	525:549	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues	525:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	10	26	theme	STAT6	1580:1584	arg1	phosphorylation					1561:1575	phosphorylation	1561:1575	phosphorylation of STAT6	1561:1584	We demonstrated that IL13 promoted phosphorylation of STAT6 to activate transcription of ST6GALNAC1.
31831633	11	27	theme	pathways	1662:1669	arg1	model					1643:1647	A computational model	1627:1647	A computational model of signaling pathways	1627:1669	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	12	28	theme	inflamed	1838:1845	arg1	colon					1861:1865	the inflamed and malignant colon	1834:1865	the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160	1834:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	3	29	gly	glycosylation	502:514	arg1	MUC1					519:522	MUC1	519:522	MUC1	519:522	It is not known what causes changes in glycosylation of MUC1.
31831633	0	30	theme	Ulcerative	95:104	arg1	Colitis					106:112	Ulcerative Colitis	95:112	Ulcerative Colitis	95:112	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	9	31	theme	blocking	1402:1409	arg1	experiments					1420:1430	blocking antibody experiments	1402:1430	blocking antibody experiments	1402:1430	Cytokine arrays and blocking antibody experiments indicated that the macrophage-dependent ST6GALNAC1 activation was mediated by IL13 and CCL17.
31831633	12	32	theme	colon	1799:1803	arg1	cells					1805:1809	colon cells	1799:1809	colon cells	1799:1809	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	2	33	theme	cancer	427:432	arg1	development					434:444	cancer development	427:444	cancer development	427:444	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	1	34	with	Patients	151:158	arg1	colitis					176:182	ulcerative colitis	165:182	ulcerative colitis	165:182	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	7	35	theme	ST6GALNAC1	1032:1041	arg1	expression					994:1003	the expression	990:1003	the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans	990:1173	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	6	36	from	effects	873:879	arg1	enzymes					931:937	glycosylation-related enzymes	909:937	glycosylation-related enzymes in colon cancer cells	909:959	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	2	37	gly	glycosylated	400:411	arg1	MUC1					413:416	this abnormally glycosylated MUC1	384:416	this abnormally glycosylated MUC1	384:416	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	12	38	theme	novel	1765:1769	arg1	cross-talk					1780:1789	a novel cellular cross-talk	1763:1789	a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160	1763:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	0	39	theme	Colon	19:23	arg1	Cells					25:29	Colon Cells	19:29	Colon Cells	19:29	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	9	40	theme	macrophage-dependent	1451:1470	arg1	activation					1483:1492	the macrophage-dependent ST6GALNAC1 activation	1447:1492	the macrophage-dependent ST6GALNAC1 activation	1447:1492	Cytokine arrays and blocking antibody experiments indicated that the macrophage-dependent ST6GALNAC1 activation was mediated by IL13 and CCL17.
31831633	6	41	theme	cancer	948:953	arg1	cells					955:959	colon cancer cells	942:959	colon cancer cells	942:959	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	4	42	theme	colon	594:598	arg1	tissues					600:606	inflamed and malignant colon tissues	571:606	inflamed and malignant colon tissues	571:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	4	43	theme	myeloid	554:560	arg1	cells					562:566	myeloid cells	554:566	myeloid cells in inflamed and malignant colon tissues	554:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	3	44	theme	MUC1	519:522	arg1	glycosylation					502:514	glycosylation	502:514	glycosylation of MUC1	502:522	It is not known what causes changes in glycosylation of MUC1.
31831633	8	45	theme	ulcerative	1194:1203	arg1	colitis					1205:1211	ulcerative colitis	1194:1211	ulcerative colitis	1194:1211	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	6	46	theme	glycosylation-related	909:929	arg1	enzymes					931:937	glycosylation-related enzymes	909:937	glycosylation-related enzymes in colon cancer cells	909:959	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	8	47	from	number	1260:1265	arg1	cells					1375:1379	colon cells	1369:1379	colon cells	1369:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	12	48	theme	related	1939:1945	arg1	Spotlight					1947:1955	CACC.See related Spotlight	1930:1955	CACC.See related Spotlight on p. 160	1930:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	12	49	from	p.	1960:1961	arg1	pathogenesis					1891:1902	the pathogenesis	1887:1902	the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160	1887:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	5	50	from	involvement	737:747	arg1	induction					791:799	the induction	787:799	the induction of aberrant MUC1 glycoforms	787:827	We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms.
31831633	8	51	theme	tissue	1222:1227	arg1	samples					1229:1235	CACC tissue samples	1217:1235	CACC tissue samples	1217:1235	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	12	52	from	Spotlight	1947:1955	arg1	p.					1960:1961	p.	1960:1961	p.	1960:1961	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	4	53	theme	macrophage-associated	659:679	arg1	cytokines					681:689	inflammatory macrophage-associated cytokines	646:689	inflammatory macrophage-associated cytokines	646:689	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	12	54	theme	ulcerative	1907:1916	arg1	colitis					1918:1924	ulcerative colitis	1907:1924	ulcerative colitis	1907:1924	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	6	55	theme	M1	884:885	arg1	macrophages					894:904	M1 and M2 macrophages	884:904	M1 and M2 macrophages	884:904	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	8	56	theme	elevated	1251:1258	arg1	number					1260:1265	the elevated number	1247:1265	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	8	57	from	ST6GALNAC1	1320:1329	arg1	cells					1375:1379	colon cells	1369:1379	colon cells	1369:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	4	58	theme	expression	625:634	arg1	levels					636:641	increased expression levels	615:641	increased expression levels of inflammatory macrophage-associated cytokines	615:689	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	2	59	theme	oncoprotein	293:303	arg1	MUC1					305:308	the oncoprotein MUC1	289:308	the oncoprotein MUC1	289:308	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	6	60	used	used	853:856	arg2	system					842:847	A coculture system	830:847	A coculture system	830:847	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	8	61	from	expression	1306:1315	arg1	cells					1375:1379	colon cells	1369:1379	colon cells	1369:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	2	62	gly	glycosylation	272:284	arg1	MUC1					305:308	the oncoprotein MUC1	289:308	the oncoprotein MUC1	289:308	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	7	63	theme	O-glycans	1165:1173	arg1	formation					1119:1127	the formation	1115:1127	the formation of tumor-associated sialyl-Tn (sTn) O-glycans	1115:1173	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	8	64	theme	macrophages	1278:1288	arg1	number					1260:1265	the elevated number	1247:1265	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	8	64	theme	macrophages	1278:1288	arg1	expression					1306:1315	high expression	1301:1315	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	8	65	theme	altered	1339:1345	arg1	glycoform					1356:1364	the altered MUC1-sTn glycoform	1335:1364	the altered MUC1-sTn glycoform on colon cells	1335:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	3	66	from	changes	491:497	arg1	glycosylation					502:514	glycosylation	502:514	glycosylation of MUC1	502:522	It is not known what causes changes in glycosylation of MUC1.
31831633	8	67	theme	glycoform	1356:1364	arg1	number					1260:1265	the elevated number	1247:1265	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	8	67	theme	glycoform	1356:1364	arg1	expression					1306:1315	high expression	1301:1315	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	7	68	link	O-linked	1079:1086	arg1	residues					1095:1102	O-linked GalNAc residues	1079:1102	O-linked GalNAc residues	1079:1102	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	7	69	theme	sialyl-Tn	1149:1157	arg1	O-glycans					1165:1173	tumor-associated sialyl-Tn (sTn) O-glycans	1132:1173	tumor-associated sialyl-Tn (sTn) O-glycans	1132:1173	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	1	70	theme	colon	240:244	arg1	CACC					254:257	CACC	254:257	CACC	254:257	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	1	70	theme	colon	240:244	arg1	cancer					246:251	colitis-associated colon cancer	221:251	colitis-associated colon cancer (CACC)	221:258	Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC).
31831633	8	71	theme	high	1301:1304	arg1	expression					1306:1315	high expression	1301:1315	the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells	1247:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	4	72	theme	normal	705:710	arg1	tissues					712:718	normal tissues	705:718	normal tissues	705:718	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	5	73	theme	macrophage-associated	752:772	arg1	cytokines					774:782	macrophage-associated cytokines	752:782	macrophage-associated cytokines	752:782	We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms.
31831633	0	74	theme	MUC1-sTn	72:79	arg1	Expression					81:90	ST6GALNAC1 and MUC1-sTn Expression	57:90	ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer	57:148	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	7	75	theme	O-linked	1079:1086	arg1	residues					1095:1102	O-linked GalNAc residues	1079:1102	O-linked GalNAc residues	1079:1102	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	4	76	theme	expression	530:539	arg1	profiling					541:549	Gene expression profiling	525:549	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues	525:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	11	77	theme	signaling	1652:1660	arg1	pathways					1662:1669	signaling pathways	1652:1669	signaling pathways	1652:1669	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	5	78	theme	MUC1	813:816	arg1	glycoforms					818:827	aberrant MUC1 glycoforms	804:827	aberrant MUC1 glycoforms	804:827	We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms.
31831633	9	79	theme	Cytokine	1382:1389	arg1	arrays					1391:1396	Cytokine arrays	1382:1396	Cytokine arrays	1382:1396	Cytokine arrays and blocking antibody experiments indicated that the macrophage-dependent ST6GALNAC1 activation was mediated by IL13 and CCL17.
31831633	8	80	from	glycoform	1356:1364	arg1	cells					1375:1379	colon cells	1369:1379	colon cells	1369:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	6	81	theme	macrophages	894:904	arg1	effects					873:879	the effects	869:879	the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells	869:959	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	5	82	theme	aberrant	804:811	arg1	glycoforms					818:827	aberrant MUC1 glycoforms	804:827	aberrant MUC1 glycoforms	804:827	We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms.
31831633	0	83	theme	Colitis-Associated	118:135	arg1	Cancer					143:148	Colitis-Associated Colon Cancer	118:148	Colitis-Associated Colon Cancer	118:148	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	9	84	theme	antibody	1411:1418	arg1	experiments					1420:1430	blocking antibody experiments	1402:1430	blocking antibody experiments	1402:1430	Cytokine arrays and blocking antibody experiments indicated that the macrophage-dependent ST6GALNAC1 activation was mediated by IL13 and CCL17.
31831633	5	85	theme	glycoforms	818:827	arg1	induction					791:799	the induction	787:799	the induction of aberrant MUC1 glycoforms	787:827	We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms.
31831633	4	86	from	tissues	600:606	arg1	profiling					541:549	Gene expression profiling	525:549	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues	525:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	4	87	theme	malignant	584:592	arg1	tissues					600:606	inflamed and malignant colon tissues	571:606	inflamed and malignant colon tissues	571:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	2	88	theme	glycosylated	400:411	arg1	MUC1					413:416	this abnormally glycosylated MUC1	384:416	this abnormally glycosylated MUC1	384:416	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	7	89	theme	glycosyltransferase	1012:1030	arg1	ST6GALNAC1					1032:1041	the glycosyltransferase ST6GALNAC1	1008:1041	the glycosyltransferase ST6GALNAC1	1008:1041	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	7	89	theme	glycosyltransferase	1012:1030	arg1	enzyme					1047:1052	an enzyme	1044:1052	an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans	1044:1173	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
31831633	4	90	from	cells	562:566	arg1	tissues					600:606	inflamed and malignant colon tissues	571:606	inflamed and malignant colon tissues	571:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	2	91	from	Changes	261:267	arg1	glycosylation					272:284	glycosylation	272:284	glycosylation of the oncoprotein MUC1	272:308	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	12	92	from	pathogenesis	1891:1902	arg1	p.					1960:1961	p.	1960:1961	p.	1960:1961	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	5	93	gly	glycoforms	818:827	arg1	MUC1					813:816	aberrant MUC1 glycoforms	804:827	aberrant MUC1 glycoforms	804:827	We analyzed the involvement of macrophage-associated cytokines in the induction of aberrant MUC1 glycoforms.
31831633	9	94	theme	ST6GALNAC1	1472:1481	arg1	activation					1483:1492	the macrophage-dependent ST6GALNAC1 activation	1447:1492	the macrophage-dependent ST6GALNAC1 activation	1447:1492	Cytokine arrays and blocking antibody experiments indicated that the macrophage-dependent ST6GALNAC1 activation was mediated by IL13 and CCL17.
31831633	6	95	theme	colon	942:946	arg1	cells					955:959	colon cancer cells	942:959	colon cancer cells	942:959	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	12	96	theme	cellular	1771:1778	arg1	cross-talk					1780:1789	a novel cellular cross-talk	1763:1789	a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160	1763:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	4	97	theme	cells	562:566	arg1	profiling					541:549	Gene expression profiling	525:549	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues	525:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	10	98	theme	ST6GALNAC1	1615:1624	arg1	transcription					1598:1610	transcription	1598:1610	transcription of ST6GALNAC1	1598:1624	We demonstrated that IL13 promoted phosphorylation of STAT6 to activate transcription of ST6GALNAC1.
31831633	11	99	theme	possible	1723:1730	arg1	therapy					1732:1738	a possible therapy	1721:1738	a possible therapy	1721:1738	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	11	99	theme	possible	1723:1730	arg1	inhibition					1707:1716	IL13 inhibition	1702:1716	IL13 inhibition	1702:1716	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	0	100	theme	ST6GALNAC1	57:66	arg1	Expression					81:90	ST6GALNAC1 and MUC1-sTn Expression	57:90	ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer	57:148	Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
31831633	8	101	theme	colitis	1205:1211	arg1	Immunostaining					1176:1189	Immunostaining	1176:1189	Immunostaining of ulcerative colitis and CACC tissue samples	1176:1235	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	4	102	theme	inflamed	571:578	arg1	tissues					600:606	inflamed and malignant colon tissues	571:606	inflamed and malignant colon tissues	571:606	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	6	103	theme	coculture	832:840	arg1	system					842:847	A coculture system	830:847	A coculture system	830:847	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	2	104	theme	ulcerative	360:369	arg1	colitis					371:377	ulcerative colitis	360:377	ulcerative colitis	360:377	Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression.
31831633	8	105	theme	CACC	1217:1220	arg1	samples					1229:1235	CACC tissue samples	1217:1235	CACC tissue samples	1217:1235	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	11	106	used	used	1689:1692	arg2	model					1643:1647	A computational model	1627:1647	A computational model of signaling pathways	1627:1669	A computational model of signaling pathways was assembled and used to test IL13 inhibition as a possible therapy.
31831633	4	107	theme	inflammatory	646:657	arg1	cytokines					681:689	inflammatory macrophage-associated cytokines	646:689	inflammatory macrophage-associated cytokines	646:689	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	8	108	theme	samples	1229:1235	arg1	Immunostaining					1176:1189	Immunostaining	1176:1189	Immunostaining of ulcerative colitis and CACC tissue samples	1176:1235	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	6	109	theme	M2	891:892	arg1	macrophages					894:904	M1 and M2 macrophages	884:904	M1 and M2 macrophages	884:904	A coculture system was used to examine the effects of M1 and M2 macrophages on glycosylation-related enzymes in colon cancer cells.
31831633	8	110	theme	colon	1369:1373	arg1	cells					1375:1379	colon cells	1369:1379	colon cells	1369:1379	Immunostaining of ulcerative colitis and CACC tissue samples confirmed the elevated number of M2-like macrophages as well as high expression of ST6GALNAC1 and the altered MUC1-sTn glycoform on colon cells.
31831633	12	111	theme	CACC.See	1930:1937	arg1	Spotlight					1947:1955	CACC.See related Spotlight	1930:1955	CACC.See related Spotlight on p. 160	1930:1965	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	12	112	from	colitis	1918:1924	arg1	p.					1960:1961	p.	1960:1961	p.	1960:1961	Our findings revealed a novel cellular cross-talk between colon cells and macrophages within the inflamed and malignant colon that contributes to the pathogenesis of ulcerative colitis and CACC.See related Spotlight on p. 160.
31831633	4	113	theme	cytokines	681:689	arg1	levels					636:641	increased expression levels	615:641	increased expression levels of inflammatory macrophage-associated cytokines	615:689	Gene expression profiling of myeloid cells in inflamed and malignant colon tissues showed increased expression levels of inflammatory macrophage-associated cytokines compared with normal tissues.
31831633	7	114	theme	M2-like	962:968	arg1	macrophages					970:980	M2-like macrophages	962:980	M2-like macrophages	962:980	M2-like macrophages induced the expression of the glycosyltransferase ST6GALNAC1, an enzyme that adds sialic acid to O-linked GalNAc residues, promoting the formation of tumor-associated sialyl-Tn (sTn) O-glycans.
30834446	9	0	theme	human	1671:1675	arg1	galectin-3					1677:1686	human galectin-3	1671:1686	human galectin-3	1671:1686	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	4	1	theme	Detailed	612:619	arg1	aspects					648:654	Detailed mechanistic and structural aspects	612:654	Detailed mechanistic and structural aspects of these processes	612:673	Detailed mechanistic and structural aspects of these processes remain undetermined.
30834446	0	2	with	interaction	58:68	arg1	glycoprotein					135:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	6	3	theme	virus	1182:1186	arg1	attachment					1188:1197	the virus attachment	1178:1197	the virus attachment	1178:1197	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	3	4	theme	viral	563:567	arg1	infection					569:577	viral infection	563:577	viral infection	563:577	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	1	5	theme	conserved	167:175	arg1	lectins					199:205	highly conserved β-galactoside-binding lectins	160:205	highly conserved β-galactoside-binding lectins	160:205	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	1	5	theme	conserved	167:175	arg1	Galectins					149:157	Galectins	149:157	Galectins	149:157	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	2	6	from	role	362:365	arg1	infection					389:397	viral infection	383:397	viral infection	383:397	In recent years, the role of galectins in viral infection has generated considerable interest.
30834446	3	7	from	participation	515:527	arg1	attachment					590:599	attachment	590:599	attachment	590:599	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	3	7	from	participation	515:527	arg1	entry					605:609	entry	605:609	entry	605:609	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	3	7	from	participation	515:527	arg1	stages					553:558	various stages	545:558	various stages	545:558	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	6	8	theme	other	974:978	arg1	rhabdoviruses					980:992	other rhabdoviruses	974:992	other rhabdoviruses	974:992	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	7	9	theme	chimeric-type	1264:1276	arg1	Drgal3-L1					1287:1295	the chimeric-type galectin Drgal3-L1	1260:1295	the chimeric-type galectin Drgal3-L1	1260:1295	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	5	10	theme	hematopoietic	836:848	arg1	IHNV					866:869	IHNV	866:869	IHNV	866:869	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	10	theme	hematopoietic	836:848	arg1	virus					859:863	infectious hematopoietic necrosis virus	825:863	infectious hematopoietic necrosis virus (IHNV)	825:870	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	10	theme	hematopoietic	836:848	arg1	rhabdovirus					875:885	a rhabdovirus	873:885	a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish	873:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	10	theme	hematopoietic	836:848	arg1	responsible					895:905	responsible	895:905	responsible	895:905	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	1	11	theme	regulatory	221:230	arg1	roles					232:236	diverse regulatory roles	213:236	diverse regulatory roles	213:236	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	9	12	theme	glycoprotein	1728:1739	arg1	ectodomain					1705:1714	the ectodomain	1701:1714	the ectodomain of the IHNV glycoprotein	1701:1739	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	9	12	theme	glycoprotein	1728:1739	arg1	glycoprotein					1728:1739	the IHNV glycoprotein	1719:1739	the IHNV glycoprotein	1719:1739	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	8	13	with	complex	1444:1450	arg1	N-acetyl-d-lactosamine					1470:1491	N-acetyl-d-lactosamine	1470:1491	N-acetyl-d-lactosamine	1470:1491	In this study, we report the structure of the complex of Drgal1-L2 with N-acetyl-d-lactosamine at 2.0 Å resolution.
30834446	10	14	theme	galectins	1805:1813	arg1	binding					1788:1794	the binding	1784:1794	the binding of these galectins to the IHNV glycoprotein	1784:1838	These models suggest mechanisms for which the binding of these galectins to the IHNV glycoprotein hinders with different potencies the viral attachment required for infection.
30834446	9	15	theme	structural	1522:1531	arg1	insight					1533:1539	structural insight	1522:1539	structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells	1522:1638	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	8	16	theme	Å	1500:1500	arg1	resolution					1502:1511	2.0 Å resolution	1496:1511	2.0 Å resolution	1496:1511	In this study, we report the structure of the complex of Drgal1-L2 with N-acetyl-d-lactosamine at 2.0 Å resolution.
30834446	5	17	theme	farmed	938:943	arg1	fish					963:966	both farmed and wild salmonid fish	933:966	both farmed and wild salmonid fish	933:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	7	18	theme	viral	1380:1384	arg1	attachment					1386:1395	viral attachment	1380:1395	viral attachment	1380:1395	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	9	19	theme	inhibitory	1550:1559	arg1	effect					1561:1566	the inhibitory effect	1546:1566	the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells	1546:1638	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	7	20	theme	galectin	1237:1244	arg1	Drgal1-L2					1246:1254	Zebrafish's proto-typical galectin Drgal1-L2	1211:1254	Zebrafish's proto-typical galectin Drgal1-L2	1211:1254	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	5	21	theme	significant	911:921	arg1	losses					923:928	significant losses	911:928	significant losses in both farmed and wild salmonid fish	911:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	0	22	theme	infectious	79:88	arg1	IHNV					120:123	IHNV	120:123	IHNV	120:123	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	0	22	theme	infectious	79:88	arg1	virus					113:117	infectious hematopoietic necrosis virus	79:117	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	7	23	gly	glycosylated	1324:1335	arg1	envelope					1337:1344	the glycosylated envelope	1320:1344	the glycosylated envelope of IHNV	1320:1352	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	9	24	theme	galectins	1577:1585	arg1	effect					1561:1566	the inhibitory effect	1546:1566	the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells	1546:1638	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	3	25	theme	pathogenic	454:463	arg1	viruses					465:471	highly pathogenic viruses	447:471	highly pathogenic viruses	447:471	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	0	26	theme	necrosis	104:111	arg1	IHNV					120:123	IHNV	120:123	IHNV	120:123	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	0	26	theme	necrosis	104:111	arg1	virus					113:117	infectious hematopoietic necrosis virus	79:117	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	9	27	theme	IHNV	1590:1593	arg1	attachment					1595:1604	IHNV attachment	1590:1604	IHNV attachment to the zebrafish epithelial cells	1590:1638	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	5	28	theme	infectious	825:834	arg1	IHNV					866:869	IHNV	866:869	IHNV	866:869	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	28	theme	infectious	825:834	arg1	virus					859:863	infectious hematopoietic necrosis virus	825:863	infectious hematopoietic necrosis virus (IHNV)	825:870	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	28	theme	infectious	825:834	arg1	rhabdovirus					875:885	a rhabdovirus	873:885	a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish	873:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	28	theme	infectious	825:834	arg1	responsible					895:905	responsible	895:905	responsible	895:905	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	29	from	losses	923:928	arg1	fish					963:966	both farmed and wild salmonid fish	933:966	both farmed and wild salmonid fish	933:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	30	theme	wild	949:952	arg1	fish					963:966	both farmed and wild salmonid fish	933:966	both farmed and wild salmonid fish	933:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	6	31	theme	glycoprotein	1059:1070	arg1	trimers					1046:1052	trimers	1046:1052	trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion	1046:1208	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	3	32	theme	invaluable	487:496	arg1	insight					498:504	invaluable insight	487:504	invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry	487:609	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	5	33	theme	necrosis	850:857	arg1	IHNV					866:869	IHNV	866:869	IHNV	866:869	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	33	theme	necrosis	850:857	arg1	virus					859:863	infectious hematopoietic necrosis virus	825:863	infectious hematopoietic necrosis virus (IHNV)	825:870	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	33	theme	necrosis	850:857	arg1	rhabdovirus					875:885	a rhabdovirus	873:885	a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish	873:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	33	theme	necrosis	850:857	arg1	responsible					895:905	responsible	895:905	responsible	895:905	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	9	34	theme	zebrafish	1613:1621	arg1	cells					1634:1638	the zebrafish epithelial cells	1609:1638	the zebrafish epithelial cells	1609:1638	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	7	35	theme	IHNV	1349:1352	arg1	envelope					1337:1344	the glycosylated envelope	1320:1344	the glycosylated envelope of IHNV	1320:1352	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	10	36	theme	viral	1877:1881	arg1	attachment					1883:1892	the viral attachment	1873:1892	the viral attachment required for infection	1873:1915	These models suggest mechanisms for which the binding of these galectins to the IHNV glycoprotein hinders with different potencies the viral attachment required for infection.
30834446	0	37	theme	galectin-1-L2	27:39	arg1	Structure					0:8	Structure	0:8	Structure of the zebrafish galectin-1-L2	0:39	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	0	37	theme	galectin-1-L2	27:39	arg1	model					45:49	model	45:49	model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	45:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	1	38	theme	microbial	320:328	arg1	infection					330:338	microbial infection	320:338	microbial infection	320:338	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	5	39	theme	galectins	799:807	arg1	role					791:794	the role	787:794	the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish	787:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	6	40	gly	glycoprotein	1059:1070	arg1	glycoprotein					1059:1070	a glycoprotein	1057:1070	a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion	1057:1208	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	6	41	link	N-linked	1094:1101	arg1	oligosaccharides					1103:1118	multiple N-linked oligosaccharides	1085:1118	multiple N-linked oligosaccharides	1085:1118	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	8	42	theme	complex	1444:1450	arg1	structure					1427:1435	the structure	1423:1435	the structure of the complex of Drgal1-L2 with N-acetyl-d-lactosamine at 2.0 Å resolution	1423:1511	In this study, we report the structure of the complex of Drgal1-L2 with N-acetyl-d-lactosamine at 2.0 Å resolution.
30834446	4	43	theme	structural	637:646	arg1	aspects					648:654	Detailed mechanistic and structural aspects	612:654	Detailed mechanistic and structural aspects of these processes	612:673	Detailed mechanistic and structural aspects of these processes remain undetermined.
30834446	8	44	theme	Drgal1-L2	1455:1463	arg1	complex					1444:1450	the complex	1440:1450	the complex of Drgal1-L2 with N-acetyl-d-lactosamine	1440:1491	In this study, we report the structure of the complex of Drgal1-L2 with N-acetyl-d-lactosamine at 2.0 Å resolution.
30834446	3	45	theme	various	545:551	arg1	attachment					590:599	attachment	590:599	attachment	590:599	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	3	45	theme	various	545:551	arg1	entry					605:609	entry	605:609	entry	605:609	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	3	45	theme	various	545:551	arg1	stages					553:558	various stages	545:558	various stages	545:558	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	10	46	gly	glycoprotein	1827:1838	arg1	glycoprotein					1827:1838	the IHNV glycoprotein	1818:1838	the IHNV glycoprotein	1818:1838	These models suggest mechanisms for which the binding of these galectins to the IHNV glycoprotein hinders with different potencies the viral attachment required for infection.
30834446	3	47	theme	galectins	532:540	arg1	participation					515:527	the participation	511:527	the participation of galectins in various stages of viral infection, including attachment and entry	511:609	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	1	48	theme	immune	257:262	arg1	homeostasis					264:274	immune homeostasis	257:274	immune homeostasis	257:274	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	9	49	from	effect	1561:1566	arg1	attachment					1595:1604	IHNV attachment	1590:1604	IHNV attachment to the zebrafish epithelial cells	1590:1638	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	6	50	theme	N-linked	1094:1101	arg1	oligosaccharides					1103:1118	multiple N-linked oligosaccharides	1085:1118	multiple N-linked oligosaccharides	1085:1118	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	3	51	theme	infection	569:577	arg1	attachment					590:599	attachment	590:599	attachment	590:599	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	3	51	theme	infection	569:577	arg1	entry					605:609	entry	605:609	entry	605:609	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	3	51	theme	infection	569:577	arg1	stages					553:558	various stages	545:558	various stages	545:558	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	4	52	theme	mechanistic	621:631	arg1	aspects					648:654	Detailed mechanistic and structural aspects	612:654	Detailed mechanistic and structural aspects of these processes	612:673	Detailed mechanistic and structural aspects of these processes remain undetermined.
30834446	1	53	theme	β-galactoside-binding	177:197	arg1	lectins					199:205	highly conserved β-galactoside-binding lectins	160:205	highly conserved β-galactoside-binding lectins	160:205	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	1	53	theme	β-galactoside-binding	177:197	arg1	Galectins					149:157	Galectins	149:157	Galectins	149:157	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	9	54	gly	glycoprotein	1728:1739	arg1	glycoprotein					1728:1739	the IHNV glycoprotein	1719:1739	the IHNV glycoprotein	1719:1739	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	6	55	theme	viral	1149:1153	arg1	infection					1155:1163	viral infection	1149:1163	viral infection	1149:1163	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	4	56	theme	processes	665:673	arg1	aspects					648:654	Detailed mechanistic and structural aspects	612:654	Detailed mechanistic and structural aspects of these processes	612:673	Detailed mechanistic and structural aspects of these processes remain undetermined.
30834446	0	57	theme	envelope	126:133	arg1	glycoprotein					135:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	10	58	theme	IHNV	1822:1825	arg1	glycoprotein					1827:1838	the IHNV glycoprotein	1818:1838	the IHNV glycoprotein	1818:1838	These models suggest mechanisms for which the binding of these galectins to the IHNV glycoprotein hinders with different potencies the viral attachment required for infection.
30834446	1	59	theme	diverse	213:219	arg1	roles					232:236	diverse regulatory roles	213:236	diverse regulatory roles	213:236	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	5	60	used	used	743:746	arg2	we					740:741	we	740:741	we	740:741	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	9	61	theme	IHNV	1723:1726	arg1	glycoprotein					1728:1739	the IHNV glycoprotein	1719:1739	the IHNV glycoprotein	1719:1739	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	5	62	from	role	791:794	arg1	infection					812:820	infection	812:820	infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish	812:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	10	63	theme	different	1853:1861	arg1	potencies					1863:1871	different potencies	1853:1871	different potencies	1853:1871	These models suggest mechanisms for which the binding of these galectins to the IHNV glycoprotein hinders with different potencies the viral attachment required for infection.
30834446	0	64	theme	interaction	58:68	arg1	Structure					0:8	Structure	0:8	Structure of the zebrafish galectin-1-L2	0:39	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	0	64	theme	interaction	58:68	arg1	model					45:49	model	45:49	model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	45:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	0	65	gly	glycoprotein	135:146	arg1	glycoprotein					135:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	7	66	theme	proto-typical	1223:1235	arg1	Drgal1-L2					1246:1254	Zebrafish's proto-typical galectin Drgal1-L2	1211:1254	Zebrafish's proto-typical galectin Drgal1-L2	1211:1254	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	0	67	theme	hematopoietic	90:102	arg1	IHNV					120:123	IHNV	120:123	IHNV	120:123	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	0	67	theme	hematopoietic	90:102	arg1	virus					113:117	infectious hematopoietic necrosis virus	79:117	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	3	68	from	Studies	436:442	arg1	viruses					465:471	highly pathogenic viruses	447:471	highly pathogenic viruses	447:471	Studies on highly pathogenic viruses have provided invaluable insight into the participation of galectins in various stages of viral infection, including attachment and entry.
30834446	8	69	from	resolution	1502:1511	arg1	structure					1427:1435	the structure	1423:1435	the structure of the complex of Drgal1-L2 with N-acetyl-d-lactosamine at 2.0 Å resolution	1423:1511	In this study, we report the structure of the complex of Drgal1-L2 with N-acetyl-d-lactosamine at 2.0 Å resolution.
30834446	6	70	theme	multiple	1085:1092	arg1	oligosaccharides					1103:1118	multiple N-linked oligosaccharides	1085:1118	multiple N-linked oligosaccharides	1085:1118	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	0	71	theme	virus	113:117	arg1	glycoprotein					135:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein	75:146	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	2	72	theme	viral	383:387	arg1	infection					389:397	viral infection	383:397	viral infection	383:397	In recent years, the role of galectins in viral infection has generated considerable interest.
30834446	0	73	theme	zebrafish	17:25	arg1	galectin-1-L2					27:39	the zebrafish galectin-1-L2	13:39	the zebrafish galectin-1-L2	13:39	Structure of the zebrafish galectin-1-L2 and model of its interaction with the infectious hematopoietic necrosis virus (IHNV) envelope glycoprotein.
30834446	1	74	theme	protective	292:301	arg1	functions					303:311	protective functions	292:311	protective functions	292:311	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	5	75	theme	salmonid	954:961	arg1	fish					963:966	both farmed and wild salmonid fish	933:966	both farmed and wild salmonid fish	933:966	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	9	76	theme	epithelial	1623:1632	arg1	cells					1634:1638	the zebrafish epithelial cells	1609:1638	the zebrafish epithelial cells	1609:1638	To gain structural insight into the inhibitory effect of these galectins on IHNV attachment to the zebrafish epithelial cells, we modeled Drgal3-L1 based on human galectin-3, as well as, the ectodomain of the IHNV glycoprotein.
30834446	7	77	theme	glycosylated	1324:1335	arg1	envelope					1337:1344	the glycosylated envelope	1320:1344	the glycosylated envelope of IHNV	1320:1352	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	2	78	theme	considerable	413:424	arg1	interest					426:433	considerable interest	413:433	considerable interest	413:433	In recent years, the role of galectins in viral infection has generated considerable interest.
30834446	6	79	theme	integral	1132:1139	arg1	role					1141:1144	an integral role	1129:1144	an integral role	1129:1144	Like other rhabdoviruses, IHNV is characterized by an envelope consisting of trimers of a glycoprotein that display multiple N-linked oligosaccharides and play an integral role in viral infection by mediating the virus attachment and fusion.
30834446	5	80	theme	model	763:767	arg1	system					769:774	a model system	761:774	a model system	761:774	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	5	80	theme	model	763:767	arg1	Zebrafish					748:756	Zebrafish	748:756	Zebrafish	748:756	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30834446	1	81	contain	have	208:211	arg2	roles					232:236	diverse regulatory roles	213:236	diverse regulatory roles	213:236	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	1	81	contain	have	208:211	arg1	lectins					199:205	highly conserved β-galactoside-binding lectins	160:205	highly conserved β-galactoside-binding lectins	160:205	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	1	81	contain	have	208:211	arg1	Galectins					149:157	Galectins	149:157	Galectins	149:157	Galectins, highly conserved β-galactoside-binding lectins, have diverse regulatory roles in development and immune homeostasis and can mediate protective functions during microbial infection.
30834446	2	82	theme	recent	344:349	arg1	years					351:355	recent years	344:355	recent years	344:355	In recent years, the role of galectins in viral infection has generated considerable interest.
30834446	7	83	theme	galectin	1278:1285	arg1	Drgal3-L1					1287:1295	the chimeric-type galectin Drgal3-L1	1260:1295	the chimeric-type galectin Drgal3-L1	1260:1295	Zebrafish's proto-typical galectin Drgal1-L2 and the chimeric-type galectin Drgal3-L1 interact directly with the glycosylated envelope of IHNV, and significantly reduce viral attachment.
30834446	2	84	theme	galectins	370:378	arg1	role					362:365	the role	358:365	the role of galectins in viral infection	358:397	In recent years, the role of galectins in viral infection has generated considerable interest.
30834446	5	85	from	gaps	721:724	arg1	knowledge					729:737	knowledge	729:737	knowledge	729:737	To address some of these gaps in knowledge, we used Zebrafish as a model system to examine the role of galectins in infection by infectious hematopoietic necrosis virus (IHNV), a rhabdovirus that is responsible for significant losses in both farmed and wild salmonid fish.
30566493	2	0	used	used	449:452	arg2	we					441:442	we	441:442	we	441:442	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	2	1	theme	selected	594:601	arg1	bNAb					603:606	a selected bNAb	592:606	a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region)	592:650	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	2	2	from	exposure	417:424	arg1	virion					433:438	the virion	429:438	the virion	429:438	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	1	3	theme	vaccine	164:170	arg1	strategies					172:181	Preventive HIV-1 vaccine strategies	147:181	Preventive HIV-1 vaccine strategies	147:181	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	4	4	theme	dominant	875:882	arg1	variant					884:890	the dominant variant	871:890	the dominant variant	871:890	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	4	theme	dominant	875:882	arg1	LR1-C1					893:898	LR1-C1	893:898	LR1-C1	893:898	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	3	5	theme	sites	818:822	arg1	loss					772:775	the loss	768:775	the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop	768:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	2	6	theme	genetics	464:471	arg1	approach					473:480	a reverse genetics approach	454:480	a reverse genetics approach	454:480	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	3	7	theme	envelope	662:669	arg1	sequences					671:679	Isolated envelope sequences	653:679	Isolated envelope sequences	653:679	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	7	8	contain	carrying	1446:1453	arg1	VLPs					1440:1443	VLPs	1440:1443	VLPs	1440:1443	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	7	8	contain	carrying	1446:1453	arg1	Particles					1429:1437	Virus Like Particles	1418:1437	Virus Like Particles (VLPs) carrying this envelope	1418:1467	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	7	8	contain	carrying	1446:1453	arg2	envelope					1460:1467	this envelope	1455:1467	this envelope	1455:1467	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	2	9	theme	MPER	639:642	arg1	region					644:649	the HIV-1 MPER region	629:649	the HIV-1 MPER region	629:649	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	3	10	theme	loop	852:855	arg1	disruption					828:837	disruption	828:837	disruption of the V1/V2 loop	828:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	10	theme	loop	852:855	arg1	sites					818:822	four potential N-linked glycosylation sites	780:822	four potential N-linked glycosylation sites	780:822	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	10	theme	loop	852:855	arg1	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	6	11	theme	neutralizing	1351:1362	arg1	activity					1364:1371	an improved neutralizing activity	1339:1371	an improved neutralizing activity	1339:1371	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	2	12	theme	HIV-1	509:513	arg1	library					549:555	an HIV-1 AC10_29 randomly mutated envelope library	506:555	an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region)	506:650	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	2	13	theme	HIV-1	633:637	arg1	region					644:649	the HIV-1 MPER region	629:649	the HIV-1 MPER region	629:649	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	4	14	theme	conformation	1089:1100	arg1	Env					1114:1116	an open conformation tier 1-like Env	1081:1116	an open conformation tier 1-like Env	1081:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	3	15	theme	N-linked	795:802	arg1	sites					818:822	four potential N-linked glycosylation sites	780:822	four potential N-linked glycosylation sites	780:822	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	15	theme	N-linked	795:802	arg1	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	8	16	theme	HIV	1679:1681	arg1	sequences					1702:1710	HIV envelope immunogen sequences	1679:1710	HIV envelope immunogen sequences that direct antibody responses to specific envelope regions	1679:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	2	17	theme	epitope	357:363	arg1	ability					343:349	the ability	339:349	the ability of an epitope to elicit effective humoral immunity	339:400	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	8	18	theme	antibody	1724:1731	arg1	responses					1733:1741	antibody responses	1724:1741	antibody responses	1724:1741	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	3	19	theme	glycosylation	804:816	arg1	sites					818:822	four potential N-linked glycosylation sites	780:822	four potential N-linked glycosylation sites	780:822	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	19	theme	glycosylation	804:816	arg1	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	0	20	theme	VLP-formulated	96:109	arg1	variant					138:144	a VLP-formulated antibody-selected envelope variant	94:144	a VLP-formulated antibody-selected envelope variant	94:144	Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
30566493	8	21	contain	has	1652:1654	arg2	potential					1660:1668	the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions	1656:1770	the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions	1656:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	8	21	contain	has	1652:1654	arg1	approach					1638:1645	a novel approach	1630:1645	a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions	1630:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	2	22	theme	mutated	532:538	arg1	library					549:555	an HIV-1 AC10_29 randomly mutated envelope library	506:555	an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region)	506:650	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	6	23	theme	AC10_29	1399:1405	arg1	env					1407:1409	the wild-type AC10_29 env	1385:1409	the wild-type AC10_29 env	1385:1409	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	6	24	from	mice	1294:1297	arg1	sera					1284:1287	sera	1284:1287	sera from mice immunized with LR1-C1 viruses	1284:1327	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	8	25	theme	novel	1632:1636	arg1	approach					1638:1645	a novel approach	1630:1645	a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions	1630:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	8	26	theme	envelope	1755:1762	arg1	regions					1764:1770	specific envelope regions	1746:1770	specific envelope regions	1746:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	6	27	dep	In	1256:1257	arg1	vivo					1259:1262	vivo	1259:1262	vivo	1259:1262	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	6	28	theme	improved	1342:1349	arg1	activity					1364:1371	an improved neutralizing activity	1339:1371	an improved neutralizing activity	1339:1371	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	7	29	theme	immunized	1527:1535	arg1	rabbits					1537:1543	immunized rabbits	1527:1543	immunized rabbits	1527:1543	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	4	30	theme	higher	975:980	arg1	affinity					982:989	higher affinity	975:989	higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env	975:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	31	theme	MPER	941:944	arg1	bNAbs					946:950	MPER bNAbs 4E10 and 2F5	941:963	MPER bNAbs 4E10 and 2F5	941:963	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	31	theme	MPER	941:944	arg1	2F5					961:963	2F5	961:963	2F5	961:963	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	31	theme	MPER	941:944	arg1	4E10					952:955	4E10	952:955	4E10	952:955	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	32	dep	bNAbs	946:950	arg1	bNAbs					946:950	MPER bNAbs 4E10 and 2F5	941:963	MPER bNAbs 4E10 and 2F5	941:963	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	32	dep	bNAbs	946:950	arg1	2F5					961:963	2F5	961:963	2F5	961:963	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	32	dep	bNAbs	946:950	arg1	4E10					952:955	4E10	952:955	4E10	952:955	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	2	33	theme	humoral	385:391	arg1	immunity					393:400	effective humoral immunity	375:400	effective humoral immunity	375:400	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	2	34	dep	bNAb	603:606	arg1	bNAb					614:617	4E10 bNAb	609:617	4E10 bNAb targeting the HIV-1 MPER region	609:649	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	7	35	theme	Like	1424:1427	arg1	VLPs					1440:1443	VLPs	1440:1443	VLPs	1440:1443	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	7	35	theme	Like	1424:1427	arg1	Particles					1429:1437	Virus Like Particles	1418:1437	Virus Like Particles (VLPs) carrying this envelope	1418:1467	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	8	36	theme	specific	1746:1753	arg1	regions					1764:1770	specific envelope regions	1746:1770	specific envelope regions	1746:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	2	37	theme	effective	375:383	arg1	immunity					393:400	effective humoral immunity	375:400	effective humoral immunity	375:400	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	3	38	theme	dominant	740:747	arg1	loss					772:775	the loss	768:775	the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop	768:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	38	theme	dominant	740:747	arg1	changes					749:755	dominant changes	740:755	dominant changes	740:755	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	2	39	theme	envelope	540:547	arg1	library					549:555	an HIV-1 AC10_29 randomly mutated envelope library	506:555	an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region)	506:650	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	0	40	with	immunization	76:87	arg1	variant					138:144	a VLP-formulated antibody-selected envelope variant	94:144	a VLP-formulated antibody-selected envelope variant	94:144	Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
30566493	3	41	link	N-linked	795:802	arg1	sites					818:822	four potential N-linked glycosylation sites	780:822	four potential N-linked glycosylation sites	780:822	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	41	link	N-linked	795:802	arg1	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	0	42	theme	humoral	12:18	arg1	response					20:27	the humoral response	8:27	the humoral response against HIV-1 toward a MPER adjacent region	8:71	Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
30566493	3	43	theme	small	724:728	arg1	loss					772:775	the loss	768:775	the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop	768:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	43	theme	small	724:728	arg1	number					730:735	a small number	722:735	a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop	722:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	0	44	theme	antibody-selected	111:127	arg1	variant					138:144	a VLP-formulated antibody-selected envelope variant	94:144	a VLP-formulated antibody-selected envelope variant	94:144	Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
30566493	1	45	theme	broadly	210:216	arg1	bNAb					241:244	bNAb	241:244	bNAb	241:244	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	1	45	theme	broadly	210:216	arg1	antibody					231:238	broadly neutralizing antibody	210:238	broadly neutralizing antibody (bNAb) responses	210:255	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	2	46	theme	reverse	456:462	arg1	approach					473:480	a reverse genetics approach	454:480	a reverse genetics approach	454:480	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	7	47	theme	antibody	1564:1571	arg1	response					1573:1580	antibody response	1564:1580	antibody response to the 4E10-proximal region	1564:1608	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	6	48	theme	In	1256:1257	arg1	studies					1264:1270	In vivo studies	1256:1270	In vivo studies	1256:1270	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	6	49	theme	wild-type	1389:1397	arg1	env					1407:1409	the wild-type AC10_29 env	1385:1409	the wild-type AC10_29 env	1385:1409	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	7	50	theme	4E10-proximal	1589:1601	arg1	region					1603:1608	the 4E10-proximal region	1585:1608	the 4E10-proximal region	1585:1608	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	1	51	theme	neutralizing	218:229	arg1	bNAb					241:244	bNAb	241:244	bNAb	241:244	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	1	51	theme	neutralizing	218:229	arg1	antibody					231:238	broadly neutralizing antibody	210:238	broadly neutralizing antibody (bNAb) responses	210:255	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	7	52	theme	detectable	1491:1500	arg1	activity					1515:1522	detectable neutralizing activity	1491:1522	detectable neutralizing activity	1491:1522	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	3	53	gly	glycosylation	804:816	arg2	sites					818:822	four potential N-linked glycosylation sites	780:822	four potential N-linked glycosylation sites	780:822	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	53	gly	glycosylation	804:816	arg2	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	53	gly	glycosylation	804:816	arg1	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	53	gly	glycosylation	804:816	arg2	four					780:783	four	780:783	four	780:783	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	5	54	dep	4E10	1231:1234	arg1	antibodies					1244:1253	antibodies	1244:1253	antibodies	1244:1253	Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies.
30566493	4	55	theme	Env	1114:1116	arg1	loop					1035:1038	the V3 loop	1028:1038	the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env	1028:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	55	theme	Env	1114:1116	arg1	consequence					1066:1076	a consequence	1064:1076	a consequence of an open conformation tier 1-like Env	1064:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	1	56	theme	antibody	231:238	arg1	responses					247:255	broadly neutralizing antibody (bNAb) responses	210:255	broadly neutralizing antibody (bNAb) responses	210:255	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	4	57	dep	showed	902:907	arg1	increased					918:926	increased	918:926	showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env	902:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	2	58	theme	increased	569:577	arg1	affinity					579:586	increased affinity	569:586	increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region)	569:650	Considering that the ability of an epitope to elicit effective humoral immunity depends on its exposure on the virion, we have used a reverse genetics approach to select variants from an HIV-1 AC10_29 randomly mutated envelope library that showed increased affinity for a selected bNAb (4E10 bNAb targeting the HIV-1 MPER region).
30566493	4	59	theme	1-like	1107:1112	arg1	Env					1114:1116	an open conformation tier 1-like Env	1081:1116	an open conformation tier 1-like Env	1081:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	3	60	theme	changes	749:755	arg1	loss					772:775	the loss	768:775	the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop	768:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	60	theme	changes	749:755	arg1	number					730:735	a small number	722:735	a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop	722:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	0	61	theme	envelope	129:136	arg1	variant					138:144	a VLP-formulated antibody-selected envelope variant	94:144	a VLP-formulated antibody-selected envelope variant	94:144	Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
30566493	4	62	theme	V3	1032:1033	arg1	consequence					1066:1076	a consequence	1064:1076	a consequence of an open conformation tier 1-like Env	1064:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	62	theme	V3	1032:1033	arg1	447-52D					1041:1047	447-52D	1041:1047	447-52D	1041:1047	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	4	62	theme	V3	1032:1033	arg1	loop					1035:1038	the V3 loop	1028:1038	the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env	1028:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	8	63	theme	envelope	1683:1690	arg1	sequences					1702:1710	HIV envelope immunogen sequences	1679:1710	HIV envelope immunogen sequences that direct antibody responses to specific envelope regions	1679:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	3	64	theme	Isolated	653:660	arg1	sequences					671:679	Isolated envelope sequences	653:679	Isolated envelope sequences	653:679	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	5	65	theme	amino	1136:1140	arg1	acids					1142:1146	the amino acids	1132:1146	the amino acids specific for the selected variant	1132:1180	Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies.
30566493	8	66	theme	immunogen	1692:1700	arg1	sequences					1702:1710	HIV envelope immunogen sequences	1679:1710	HIV envelope immunogen sequences that direct antibody responses to specific envelope regions	1679:1770	Our data establish a novel approach that has the potential to yield HIV envelope immunogen sequences that direct antibody responses to specific envelope regions.
30566493	3	67	theme	V1/V2	846:850	arg1	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	5	68	theme	specific	1148:1155	arg1	acids					1142:1146	the amino acids	1132:1146	the amino acids specific for the selected variant	1132:1180	Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies.
30566493	6	69	theme	LR1-C1	1314:1319	arg1	viruses					1321:1327	LR1-C1 viruses	1314:1327	LR1-C1 viruses	1314:1327	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	4	70	theme	open	1084:1087	arg1	Env					1114:1116	an open conformation tier 1-like Env	1081:1116	an open conformation tier 1-like Env	1081:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	3	71	theme	disruption	828:837	arg1	loss					772:775	the loss	768:775	the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop	768:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	72	theme	potential	785:793	arg1	sites					818:822	four potential N-linked glycosylation sites	780:822	four potential N-linked glycosylation sites	780:822	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	3	72	theme	potential	785:793	arg1	loop					852:855	the V1/V2 loop	842:855	the V1/V2 loop	842:855	Isolated envelope sequences were analyzed by deep-sequencing showing a small number of dominant changes, including the loss of four potential N-linked glycosylation sites and disruption of the V1/V2 loop.
30566493	0	73	theme	adjacent	57:64	arg1	region					66:71	a MPER adjacent region	50:71	a MPER adjacent region	50:71	Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
30566493	6	74	contain	possessed	1329:1337	arg1	sera					1284:1287	sera	1284:1287	sera from mice immunized with LR1-C1 viruses	1284:1327	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	6	74	contain	possessed	1329:1337	arg2	activity					1364:1371	an improved neutralizing activity	1339:1371	an improved neutralizing activity	1339:1371	In vivo studies showed that sera from mice immunized with LR1-C1 viruses possessed an improved neutralizing activity compared to the wild-type AC10_29 env.
30566493	1	75	theme	Preventive	147:156	arg1	strategies					172:181	Preventive HIV-1 vaccine strategies	147:181	Preventive HIV-1 vaccine strategies	147:181	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	5	76	theme	increased	1205:1213	arg1	sensitivity					1215:1225	an increased sensitivity	1202:1225	an increased sensitivity for 4E10 and 2F5 antibodies	1202:1253	Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies.
30566493	7	77	theme	neutralizing	1502:1513	arg1	activity					1515:1522	detectable neutralizing activity	1491:1522	detectable neutralizing activity	1491:1522	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	0	78	theme	MPER	52:55	arg1	region					66:71	a MPER adjacent region	50:71	a MPER adjacent region	50:71	Guiding the humoral response against HIV-1 toward a MPER adjacent region by immunization with a VLP-formulated antibody-selected envelope variant.
30566493	7	79	theme	Virus	1418:1422	arg1	VLPs					1440:1443	VLPs	1440:1443	VLPs	1440:1443	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	7	79	theme	Virus	1418:1422	arg1	Particles					1429:1437	Virus Like Particles	1418:1437	Virus Like Particles (VLPs) carrying this envelope	1418:1467	While Virus Like Particles (VLPs) carrying this envelope were unable to induce detectable neutralizing activity in immunized rabbits, one animal showed antibody response to the 4E10-proximal region.
30566493	5	80	theme	selected	1165:1172	arg1	variant					1174:1180	the selected variant	1161:1180	the selected variant	1161:1180	Furthermore, the amino acids specific for the selected variant are associated with an increased sensitivity for 4E10 and 2F5 antibodies.
30566493	4	81	theme	tier	1102:1105	arg1	Env					1114:1116	an open conformation tier 1-like Env	1081:1116	an open conformation tier 1-like Env	1081:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	1	82	theme	HIV-1	158:162	arg1	strategies					172:181	Preventive HIV-1 vaccine strategies	147:181	Preventive HIV-1 vaccine strategies	147:181	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
30566493	4	83	theme	additional	998:1007	arg1	antibody					1009:1016	an additional antibody	995:1016	an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env	995:1116	Accordingly, the dominant variant (LR1-C1), showed not only increased affinity for MPER bNAbs 4E10 and 2F5, but also higher affinity for an additional antibody targeting the V3 loop (447-52D) that could be a consequence of an open conformation tier 1-like Env.
30566493	1	84	theme	responses	247:255	arg1	elicitation					195:205	the elicitation	191:205	the elicitation of broadly neutralizing antibody (bNAb) responses	191:255	Preventive HIV-1 vaccine strategies rely on the elicitation of broadly neutralizing antibody (bNAb) responses, but their induction in vivo by vaccination remains challenging.
29597345	4	0	theme	DNA	810:812	arg1	methylation					814:824	DNA methylation	810:824	DNA methylation	810:824	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	2	1	theme	residential	309:319	arg1	exposure					321:328	residential exposure	309:328	residential exposure to PM smaller than 10 μm (PM10)	309:360	Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10).
29597345	6	2	theme	associated	1171:1180	arg1	sites					1186:1190	the 100 strongest associated CpG sites	1153:1190	the 100 strongest associated CpG sites of the longitudinal model	1153:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	6	2	theme	associated	1171:1180	arg1	model					1212:1216	the longitudinal model	1195:1216	the longitudinal model	1195:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	5	3	dep	groups	1050:1055	arg1	=					1090:1090	=	1090:1090	=	1090:1090	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	3	4	theme	cord	585:588	arg1	blood					590:594	cord blood	585:594	cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	585:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	4	5	theme	concordant	877:886	arg1	exposure					895:902	concordant annual exposure	877:902	concordant annual exposure	877:902	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	3	6	theme	consortium	564:573	arg1	Study					421:425	the Avon Longitudinal Study	399:425	the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	399:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	2	7	theme	methylome-wide	237:250	arg1	analyses					252:259	methylome-wide analyses	237:259	methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10)	237:360	Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10).
29597345	3	8	from	Piccolipiù	641:650	arg1	blood					590:594	cord blood	585:594	cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	585:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	9	theme	enriched	1227:1234	arg1	pathways					1236:1243	enriched pathways	1227:1243	enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1	1227:1303	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	1	10	theme	restricted	169:178	arg1	growth					186:191	restricted fetal growth	169:191	restricted fetal growth	169:191	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	2	11	from	analyses	252:259	arg1	relation					297:304	relation	297:304	relation to residential exposure to PM smaller than 10 μm (PM10)	297:360	Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10).
29597345	7	12	theme	PM10	1344:1347	arg1	exposure					1349:1356	residential PM10 exposure	1332:1356	residential PM10 exposure in early life	1332:1370	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	7	13	theme	Transferase	1478:1488	arg1	gene					1490:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	5	14	theme	studied	1038:1044	arg1	groups					1050:1055	the three studied age groups	1028:1055	the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8)	1028:1103	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	1	15	theme	airborne	111:118	arg1	matter					132:137	airborne particulate matter	111:137	airborne particulate matter (PM)	111:142	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	1	15	theme	airborne	111:118	arg1	PM					140:141	PM	140:141	PM	140:141	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	7	16	theme	O-Linked	1449:1456	arg1	N-Acetylglucosamine					1458:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	7	17	theme	gene	1490:1493	arg1	methylation					1380:1390	methylation	1380:1390	methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1380:1493	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	3	18	theme	=	502:502	arg1	n					500:500	n = 757	500:506	n = 757	500:506	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	19	theme	p53	1280:1282	arg1	signaling					1284:1292	p53 signaling	1280:1292	p53 signaling	1280:1292	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	7	20	theme	Domain	1433:1438	arg1	N-Acetylglucosamine					1458:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	0	21	theme	Time	63:66	arg1	Points					68:73	Three Time Points	57:73	Three Time Points in Early Life	57:87	DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life.
29597345	3	22	theme	=	634:634	arg1	n					632:632	n = 84	632:637	n = 84	632:637	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	22	theme	=	634:634	arg1	INMA					625:628	INMA	625:628	INMA ( n = 84)	625:638	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	7	23	theme	located	1414:1420	arg1	gene					1490:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	4	24	theme	CpG	716:718	arg1	sites					720:724	significant CpG sites	704:724	significant CpG sites	704:724	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	7	25	theme	CpG	1399:1401	arg1	gene					1490:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	3	26	from	ONAGE	607:611	arg1	blood					590:594	cord blood	585:594	cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	585:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	5	27	theme	raw	1078:1080	arg1	p-value					1082:1088	raw p-value	1078:1088	raw p-value	1078:1088	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	0	28	theme	DNA	0:2	arg1	Methylome					4:12	DNA Methylome	0:12	DNA Methylome	0:12	DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life.
29597345	3	29	from	age	493:495	arg1	blood					484:488	blood	484:488	blood at age 7	484:497	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	30	theme	Avon	403:406	arg1	Study					421:425	the Avon Longitudinal Study	399:425	the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	399:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	5	31	theme	CpG	930:932	arg1	cg21785536					934:943	The CpG cg21785536	926:943	The CpG cg21785536	926:943	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	6	32	dep	associated	1171:1180	arg1	strongest					1161:1169	strongest	1161:1169	strongest	1161:1169	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	4	33	theme	PM10	775:778	arg1	exposure					780:787	maternal PM10 exposure	766:787	maternal PM10 exposure	766:787	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	3	34	theme	Pregnancy	430:438	arg1	Study					421:425	the Avon Longitudinal Study	399:425	the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	399:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	0	35	theme	Particulate	35:45	arg1	Matter					47:52	Particulate Matter	35:52	Particulate Matter	35:52	DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life.
29597345	3	36	theme	Study	421:425	arg1	participants					383:394	participants	383:394	participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	383:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	37	theme	longitudinal	1199:1210	arg1	model					1212:1216	the longitudinal model	1195:1216	the longitudinal model	1195:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	5	38	theme	PM10	975:978	arg1	exposure					980:987	PM10 exposure	975:987	PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8)	975:1103	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	3	39	theme	cohort	557:562	arg1	consortium					564:573	the EXPOsOMICS birth cohort consortium	536:573	the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	536:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	5	40	theme	×	1097:1097	arg1	10-8					1099:1102	3.82 × 10-8	1092:1102	3.82 × 10-8	1092:1102	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	3	41	theme	Childhood	444:452	arg1	Study					421:425	the Avon Longitudinal Study	399:425	the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	399:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	42	theme	CpG	1182:1184	arg1	sites					1186:1190	the 100 strongest associated CpG sites	1153:1190	the 100 strongest associated CpG sites of the longitudinal model	1153:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	6	42	theme	CpG	1182:1184	arg1	model					1212:1216	the longitudinal model	1195:1216	the longitudinal model	1195:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	4	43	theme	cord	829:832	arg1	blood					834:838	cord blood	829:838	cord blood	829:838	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	3	44	theme	EXPOsOMICS	540:549	arg1	consortium					564:573	the EXPOsOMICS birth cohort consortium	536:573	the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	536:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	2	45	theme	cord	264:267	arg1	analyses					252:259	methylome-wide analyses	237:259	methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10)	237:360	Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10).
29597345	4	46	theme	annual	888:893	arg1	exposure					895:902	concordant annual exposure	877:902	concordant annual exposure	877:902	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	3	47	theme	cord	463:466	arg1	blood					468:472	cord blood	463:472	cord blood	463:472	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	48	theme	GABAergic	1261:1269	arg1	synapse					1271:1277	the GABAergic synapse	1257:1277	the GABAergic synapse	1257:1277	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	3	49	from	Rhea	666:669	arg1	blood					590:594	cord blood	585:594	cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	585:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	2	50	theme	blood	284:288	arg1	DNA					290:292	children's blood DNA	273:292	children's blood DNA	273:292	Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10).
29597345	7	51	theme	early	1361:1365	arg1	life					1367:1370	early life	1361:1370	early life	1361:1370	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	4	52	theme	DNA	857:859	arg1	methylation					861:871	DNA methylation	857:871	DNA methylation	857:871	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	3	53	theme	=	477:477	arg1	n					475:475	n = 780	475:481	n = 780	475:481	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	0	54	from	Points	68:73	arg1	Life					84:87	Early Life	78:87	Early Life	78:87	DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life.
29597345	3	55	theme	ENVIR	601:605	arg1	ONAGE					607:611	ENVIR ONAGE	601:611	ENVIR ONAGE ( n = 197)	601:622	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	55	theme	ENVIR	601:605	arg1	n					615:615	n = 197	615:621	n = 197	615:621	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	4	56	dep	identify	695:702	arg1	studying					848:855	studying	848:855	studying DNA methylation and concordant annual exposure at 7 and 15-17 years	848:923	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	4	56	dep	identify	695:702	arg1	meta-analyzing					730:743	meta-analyzing	730:743	meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood	730:838	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	1	57	theme	fetal	180:184	arg1	growth					186:191	restricted fetal growth	169:191	restricted fetal growth	169:191	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	7	58	theme	residential	1332:1342	arg1	exposure					1349:1356	residential PM10 exposure	1332:1356	residential PM10 exposure in early life	1332:1370	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	1	59	theme	Maternal	90:97	arg1	exposure					99:106	Maternal exposure	90:106	Maternal exposure to airborne particulate matter (PM)	90:142	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	3	60	theme	=	617:617	arg1	ONAGE					607:611	ENVIR ONAGE	601:611	ENVIR ONAGE ( n = 197)	601:622	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	60	theme	=	617:617	arg1	n					615:615	n = 197	615:621	n = 197	615:621	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	61	from	analyses	1114:1121	arg1	genes					1144:1148	the corresponding genes	1126:1148	the corresponding genes	1126:1148	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	3	62	theme	=	656:656	arg1	n					654:654	n = 99	654:659	n = 99	654:659	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	62	theme	=	656:656	arg1	Piccolipiù					641:650	Piccolipiù	641:650	Piccolipiù ( n = 99)	641:660	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	5	63	theme	age	1046:1048	arg1	groups					1050:1055	the three studied age groups	1028:1055	the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8)	1028:1103	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	6	64	theme	Pathway	1106:1112	arg1	analyses					1114:1121	Pathway analyses	1106:1121	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model	1106:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	1	65	theme	particulate	120:130	arg1	matter					132:137	airborne particulate matter	111:137	airborne particulate matter (PM)	111:142	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	1	65	theme	particulate	120:130	arg1	PM					140:141	PM	140:141	PM	140:141	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	5	66	theme	longitudinal	997:1008	arg1	model					1010:1014	a longitudinal model	995:1014	a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8)	995:1103	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	4	67	from	methylation	814:824	arg1	blood					834:838	cord blood	829:838	cord blood	829:838	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	7	68	theme	Specific	1440:1447	arg1	N-Acetylglucosamine					1458:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	0	69	theme	Early	78:82	arg1	Life					84:87	Early Life	78:87	Early Life	78:87	DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life.
29597345	7	70	theme	EGF	1429:1431	arg1	N-Acetylglucosamine					1458:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	the EGF Domain Specific O-Linked N-Acetylglucosamine	1425:1476	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	3	71	theme	=	675:675	arg1	n					673:673	n = 75	673:678	n = 75	673:678	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	71	theme	=	675:675	arg1	Rhea					666:669	Rhea	666:669	Rhea ( n = 75)	666:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	7	72	from	exposure	1349:1356	arg1	life					1367:1370	early life	1361:1370	early life	1361:1370	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	4	73	theme	significant	704:714	arg1	sites					720:724	significant CpG sites	704:724	significant CpG sites	704:724	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	7	74	theme	cg21785536	1403:1412	arg1	gene					1490:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene	1395:1493	We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.
29597345	4	75	from	pregnancy	796:804	arg1	blood					834:838	cord blood	829:838	cord blood	829:838	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	3	76	dep	ALSPAC	455:460	arg1	age					512:514	age 15-17	512:520	age 15-17	512:520	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	76	dep	ALSPAC	455:460	arg1	n					523:523	n = 850	523:529	n = 850	523:529	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	76	dep	ALSPAC	455:460	arg1	n					500:500	n = 757	500:506	n = 757	500:506	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	76	dep	ALSPAC	455:460	arg1	blood					484:488	blood	484:488	blood at age 7	484:497	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	76	dep	ALSPAC	455:460	arg1	blood					468:472	cord blood	463:472	cord blood	463:472	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	76	dep	ALSPAC	455:460	arg1	n					475:475	n = 780	475:481	n = 780	475:481	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	3	77	theme	Longitudinal	408:419	arg1	Study					421:425	the Avon Longitudinal Study	399:425	the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	399:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	78	theme	corresponding	1130:1142	arg1	genes					1144:1148	the corresponding genes	1126:1148	the corresponding genes	1126:1148	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	5	79	dep	=	1090:1090	arg1	%					1062:1062	-1.2%	1058:1062	-1.2% per 10 μg/m3	1058:1075	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	4	80	theme	maternal	766:773	arg1	exposure					780:787	maternal PM10 exposure	766:787	maternal PM10 exposure	766:787	We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years.
29597345	3	81	from	INMA	625:628	arg1	blood					590:594	cord blood	585:594	cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	585:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	6	82	theme	model	1212:1216	arg1	sites					1186:1190	the 100 strongest associated CpG sites	1153:1190	the 100 strongest associated CpG sites of the longitudinal model	1153:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	6	82	theme	model	1212:1216	arg1	model					1212:1216	the longitudinal model	1195:1216	the longitudinal model	1195:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
29597345	3	83	theme	=	525:525	arg1	n					523:523	n = 850	523:529	n = 850	523:529	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	2	84	theme	DNA	290:292	arg1	analyses					252:259	methylome-wide analyses	237:259	methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10)	237:360	Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10).
29597345	1	85	theme	reduced	197:203	arg1	birthweight					205:215	reduced birthweight	197:215	reduced birthweight	197:215	Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight.
29597345	3	86	theme	birth	551:555	arg1	consortium					564:573	the EXPOsOMICS birth cohort consortium	536:573	the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75)	536:679	This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75).
29597345	5	87	theme	3.82	1092:1095	arg1	×					1097:1097	×	1097:1097	×	1097:1097	The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8).
29597345	6	88	theme	sites	1186:1190	arg1	analyses					1114:1121	Pathway analyses	1106:1121	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model	1106:1216	Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1.
28926587	4	0	theme	gene	863:866	arg1	orthologs					833:841	two zebrafish orthologs	819:841	two zebrafish orthologs of the human B3GLCT gene	819:866	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	4	0	theme	gene	863:866	arg1	b3glctb					881:887	b3glctb	881:887	b3glctb	881:887	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	4	0	theme	gene	863:866	arg1	b3glcta					869:875	b3glcta	869:875	b3glcta	869:875	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	11	1	theme	Transcriptome	1694:1706	arg1	analyses					1708:1715	Transcriptome analyses	1694:1715	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos	1694:1769	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	13	2	theme	same	2020:2023	arg1	time					2025:2028	the same time	2016:2028	the same time	2016:2028	At the same time, complete b3glct deficiency in zebrafish appears to be inconsequential and possibly compensated for by a yet unknown mechanism.
28926587	11	3	theme	head	1720:1723	arg1	tissues					1735:1741	head and trunk tissues	1720:1741	head and trunk tissues	1720:1741	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	2	4	link	O-linked	543:550	arg1	fucose					552:557	O-linked fucose	543:557	O-linked fucose on thrombospondin type 1 repeats (TSRs)	543:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	3	5	theme	molecular	700:708	arg1	processes					710:718	the exact molecular processes	690:718	the exact molecular processes affected in PPS	690:734	B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood.
28926587	4	6	dep	identification	780:793	arg1	the					776:778	the	776:778	the	776:778	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	4	7	theme	human	850:854	arg1	gene					863:866	the human B3GLCT gene	846:866	the human B3GLCT gene	846:866	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	1	8	theme	autosomal	173:181	arg1	disease					193:199	a rare autosomal recessive disease	166:199	a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects	166:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	1	8	theme	autosomal	173:181	arg1	Syndrome					148:155	Peters Plus Syndrome	136:155	Peters Plus Syndrome (PPS)	136:161	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	2	9	theme	thrombospondin	562:575	arg1	type					577:580	thrombospondin type 1 repeats (TSRs)	562:597	thrombospondin type 1 repeats (TSRs)	562:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	8	10	theme	single	1442:1447	arg1	knockouts					1467:1475	single and double b3glct knockouts	1442:1475	single and double b3glct knockouts	1442:1475	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	10	11	theme	homozygous	1658:1667	arg1	fish					1669:1672	b3glct-/- homozygous fish	1648:1672	b3glct-/- homozygous fish	1648:1672	Surprisingly, b3glct-/- homozygous fish developed normally.
28926587	8	12	theme	double	1453:1458	arg1	knockouts					1467:1475	single and double b3glct knockouts	1442:1475	single and double b3glct knockouts	1442:1475	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	11	13	theme	regulated	1808:1816	arg1	transcripts					1818:1828	483 shared differentially regulated transcripts	1782:1828	483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos	1782:1902	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	1	14	theme	Plus	143:146	arg1	disease					193:199	a rare autosomal recessive disease	166:199	a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects	166:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	1	14	theme	Plus	143:146	arg1	PPS					158:160	PPS	158:160	PPS	158:160	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	1	14	theme	Plus	143:146	arg1	Syndrome					148:155	Peters Plus Syndrome	136:155	Peters Plus Syndrome (PPS)	136:161	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	5	15	theme	b3glctb	906:912	arg1	genes					914:918	The b3glcta and b3glctb genes	890:918	The b3glcta and b3glctb genes	890:918	The b3glcta and b3glctb genes encode for 496-aa and 493-aa proteins with 65% and 57% identity to human B3GLCT, respectively.
28926587	7	16	from	embryos	1217:1223	arg1	extracts					1194:1201	extracts	1194:1201	extracts from wildtype embryos	1194:1223	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	7	17	theme	functional	1339:1348	arg1	conservation					1350:1361	functional conservation	1339:1361	functional conservation with human B3GLCT	1339:1379	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	9	18	dep	in	1608:1609	arg1	vitro					1611:1615	vitro	1611:1615	vitro	1611:1615	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	11	19	theme	shared	1786:1791	arg1	transcripts					1818:1828	483 shared differentially regulated transcripts	1782:1828	483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos	1782:1902	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	7	20	with	conservation	1350:1361	arg1	B3GLCT					1374:1379	human B3GLCT	1368:1379	human B3GLCT	1368:1379	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	2	21	theme	glucose	502:508	arg1	attachment					488:497	the attachment	484:497	the attachment of glucose	484:508	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	8	22	theme	TALEN-induced	1498:1510	arg1	editing					1519:1525	TALEN-induced genome editing	1498:1525	TALEN-induced genome editing	1498:1525	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	0	23	theme	B3GLCT	91:96	arg1	gene					98:101	the human Beta 3-Glucosyltransferase B3GLCT gene	54:101	the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome	54:133	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	1	24	theme	systemic	342:349	arg1	defects					351:357	other highly variable systemic defects	320:357	other highly variable systemic defects	320:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	12	25	theme	genes	1978:1982	arg1	function					1952:1959	function	1952:1959	function	1952:1959	The presented data show that both sequence and function of B3GLCT/b3glct genes is conserved in vertebrates.
28926587	12	25	theme	genes	1978:1982	arg1	sequence					1939:1946	sequence	1939:1946	sequence	1939:1946	The presented data show that both sequence and function of B3GLCT/b3glct genes is conserved in vertebrates.
28926587	9	26	theme	homozygous	1549:1558	arg1	embryos					1570:1576	double homozygous b3glct-/- embryos	1542:1576	double homozygous b3glct-/- embryos	1542:1576	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	7	27	theme	human	1368:1372	arg1	B3GLCT					1374:1379	human B3GLCT	1368:1379	human B3GLCT	1368:1379	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	7	28	dep	In	1146:1147	arg1	vitro					1149:1153	vitro	1149:1153	vitro	1149:1153	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	2	29	theme	glycosidic	521:530	arg1	linkage					532:538	a β1-3 glycosidic linkage	514:538	a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs)	514:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	9	30	theme	complete	1591:1598	arg1	loss					1600:1603	complete loss	1591:1603	complete loss of in vitro b3glct activity	1591:1631	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	0	31	theme	3-Glucosyltransferase	69:89	arg1	gene					98:101	the human Beta 3-Glucosyltransferase B3GLCT gene	54:101	the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome	54:133	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	0	32	theme	Functional	0:9	arg1	characterization					11:26	Functional characterization	0:26	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.	0:134	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	1	33	theme	characteristic	264:277	arg1	features					286:293	characteristic facial features	264:293	characteristic facial features	264:293	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	7	34	gly	O-fucosylated	1309:1321	arg1	TSR					1323:1325	an O-fucosylated TSR	1306:1325	an O-fucosylated TSR	1306:1325	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	11	35	theme	b3glct-/-	1746:1754	arg1	embryos					1763:1769	b3glct-/- 24-hpf embryos	1746:1769	b3glct-/- 24-hpf embryos	1746:1769	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	3	36	theme	ER	651:652	arg1	mechanism					670:678	a non-canonical ER quality control mechanism	635:678	a non-canonical ER quality control mechanism	635:678	B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood.
28926587	8	37	theme	developmental	1399:1411	arg1	role					1413:1416	the developmental role	1395:1416	the developmental role of the zebrafish genes	1395:1439	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	0	38	theme	orthologs	41:49	arg1	characterization					11:26	Functional characterization	0:26	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.	0:134	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	1	39	theme	developmental	296:308	arg1	delay					310:314	developmental delay	296:314	developmental delay	296:314	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	9	40	theme	activity	1624:1631	arg1	loss					1600:1603	complete loss	1591:1603	complete loss of in vitro b3glct activity	1591:1631	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	0	41	theme	Beta	64:67	arg1	gene					98:101	the human Beta 3-Glucosyltransferase B3GLCT gene	54:101	the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome	54:133	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	4	42	theme	zebrafish	823:831	arg1	orthologs					833:841	two zebrafish orthologs	819:841	two zebrafish orthologs of the human B3GLCT gene	819:866	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	4	42	theme	zebrafish	823:831	arg1	b3glctb					881:887	b3glctb	881:887	b3glctb	881:887	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	4	42	theme	zebrafish	823:831	arg1	b3glcta					869:875	b3glcta	869:875	b3glcta	869:875	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	11	43	from	compensation	1854:1865	arg1	embryos					1896:1902	these embryos	1890:1902	these embryos	1890:1902	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	2	44	from	mutations	402:410	arg1	gene					426:429	the B3GLCT gene	415:429	the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs)	415:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	8	45	theme	zebrafish	1425:1433	arg1	genes					1435:1439	the zebrafish genes	1421:1439	the zebrafish genes	1421:1439	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	6	46	from	presence	1099:1106	arg1	tissues					1121:1127	embryonic tissues	1111:1127	embryonic tissues affected in PPS	1111:1143	Expression studies demonstrate that both orthologs are widely expressed with strong presence in embryonic tissues affected in PPS.
28926587	1	47	theme	ocular	218:223	arg1	defects					225:231	ocular defects	218:231	ocular defects	218:231	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	12	48	theme	presented	1909:1917	arg1	data					1919:1922	The presented data	1905:1922	The presented data	1905:1922	The presented data show that both sequence and function of B3GLCT/b3glct genes is conserved in vertebrates.
28926587	3	49	theme	control	662:668	arg1	mechanism					670:678	a non-canonical ER quality control mechanism	635:678	a non-canonical ER quality control mechanism	635:678	B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood.
28926587	2	50	dep	type	577:580	arg1	TSRs					593:596	TSRs	593:596	TSRs	593:596	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	2	50	dep	type	577:580	arg1	repeats					584:590	repeats	584:590	thrombospondin type 1 repeats (TSRs)	562:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	5	51	theme	%	973:973	arg1	identity					975:982	57% identity	971:982	57% identity to human B3GLCT	971:998	The b3glcta and b3glctb genes encode for 496-aa and 493-aa proteins with 65% and 57% identity to human B3GLCT, respectively.
28926587	11	52	theme	tissues	1735:1741	arg1	analyses					1708:1715	Transcriptome analyses	1694:1715	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos	1694:1769	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	3	53	theme	exact	694:698	arg1	processes					710:718	the exact molecular processes	690:718	the exact molecular processes affected in PPS	690:734	B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood.
28926587	2	54	theme	Classic	360:366	arg1	PPS					368:370	Classic PPS	360:370	Classic PPS	360:370	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	7	55	contain	contain	1225:1231	arg2	enzyme					1247:1252	active b3glct enzyme	1233:1252	active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT	1233:1379	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	7	55	contain	contain	1225:1231	arg1	extracts					1194:1201	extracts	1194:1201	extracts from wildtype embryos	1194:1223	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	4	56	theme	B3GLCT	856:861	arg1	gene					863:866	the human B3GLCT gene	846:866	the human B3GLCT gene	846:866	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	7	57	theme	active	1233:1238	arg1	enzyme					1247:1252	active b3glct enzyme	1233:1252	active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT	1233:1379	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	13	58	theme	complete	2031:2038	arg1	deficiency					2047:2056	complete b3glct deficiency	2031:2056	complete b3glct deficiency in zebrafish	2031:2069	At the same time, complete b3glct deficiency in zebrafish appears to be inconsequential and possibly compensated for by a yet unknown mechanism.
28926587	4	59	theme	orthologs	833:841	arg1	identification					780:793	identification	780:793	identification	780:793	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	4	59	theme	orthologs	833:841	arg1	characterization					799:814	characterization	799:814	characterization	799:814	Here we report the identification and characterization of two zebrafish orthologs of the human B3GLCT gene, b3glcta and b3glctb.
28926587	1	60	theme	rare	168:171	arg1	disease					193:199	a rare autosomal recessive disease	166:199	a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects	166:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	1	60	theme	rare	168:171	arg1	Syndrome					148:155	Peters Plus Syndrome	136:155	Peters Plus Syndrome (PPS)	136:161	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	11	61	theme	b3glct	1871:1876	arg1	function					1878:1885	b3glct function	1871:1885	b3glct function	1871:1885	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	1	62	theme	recessive	183:191	arg1	disease					193:199	a rare autosomal recessive disease	166:199	a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects	166:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	1	62	theme	recessive	183:191	arg1	Syndrome					148:155	Peters Plus Syndrome	136:155	Peters Plus Syndrome (PPS)	136:161	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	6	63	theme	embryonic	1111:1119	arg1	tissues					1121:1127	embryonic tissues	1111:1127	embryonic tissues affected in PPS	1111:1143	Expression studies demonstrate that both orthologs are widely expressed with strong presence in embryonic tissues affected in PPS.
28926587	13	64	from	deficiency	2047:2056	arg1	zebrafish					2061:2069	zebrafish	2061:2069	zebrafish	2061:2069	At the same time, complete b3glct deficiency in zebrafish appears to be inconsequential and possibly compensated for by a yet unknown mechanism.
28926587	2	65	theme	O-linked	543:550	arg1	fucose					552:557	O-linked fucose	543:557	O-linked fucose on thrombospondin type 1 repeats (TSRs)	543:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	8	66	theme	b3glct	1460:1465	arg1	knockouts					1467:1475	single and double b3glct knockouts	1442:1475	single and double b3glct knockouts	1442:1475	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	10	67	theme	b3glct-/-	1648:1656	arg1	fish					1669:1672	b3glct-/- homozygous fish	1648:1672	b3glct-/- homozygous fish	1648:1672	Surprisingly, b3glct-/- homozygous fish developed normally.
28926587	5	68	theme	b3glcta	894:900	arg1	genes					914:918	The b3glcta and b3glctb genes	890:918	The b3glcta and b3glctb genes	890:918	The b3glcta and b3glctb genes encode for 496-aa and 493-aa proteins with 65% and 57% identity to human B3GLCT, respectively.
28926587	1	69	theme	Peters	136:141	arg1	disease					193:199	a rare autosomal recessive disease	166:199	a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects	166:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	1	69	theme	Peters	136:141	arg1	PPS					158:160	PPS	158:160	PPS	158:160	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	1	69	theme	Peters	136:141	arg1	Syndrome					148:155	Peters Plus Syndrome	136:155	Peters Plus Syndrome (PPS)	136:161	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	9	70	theme	b3glct-/-	1560:1568	arg1	embryos					1570:1576	double homozygous b3glct-/- embryos	1542:1576	double homozygous b3glct-/- embryos	1542:1576	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	6	71	theme	strong	1092:1097	arg1	presence					1099:1106	strong presence	1092:1106	strong presence in embryonic tissues affected in PPS	1092:1143	Expression studies demonstrate that both orthologs are widely expressed with strong presence in embryonic tissues affected in PPS.
28926587	7	72	theme	wildtype	1208:1215	arg1	embryos					1217:1223	wildtype embryos	1208:1223	wildtype embryos	1208:1223	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	8	73	theme	genome	1512:1517	arg1	editing					1519:1525	TALEN-induced genome editing	1498:1525	TALEN-induced genome editing	1498:1525	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	0	74	theme	gene	98:101	arg1	characterization					11:26	Functional characterization	0:26	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.	0:134	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	1	75	theme	variable	333:340	arg1	defects					351:357	other highly variable systemic defects	320:357	other highly variable systemic defects	320:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	9	76	theme	double	1542:1547	arg1	embryos					1570:1576	double homozygous b3glct-/- embryos	1542:1576	double homozygous b3glct-/- embryos	1542:1576	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	11	77	theme	24-hpf	1756:1761	arg1	embryos					1763:1769	b3glct-/- 24-hpf embryos	1746:1769	b3glct-/- 24-hpf embryos	1746:1769	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	13	78	theme	unknown	2139:2145	arg1	mechanism					2147:2155	a yet unknown mechanism	2133:2155	a yet unknown mechanism	2133:2155	At the same time, complete b3glct deficiency in zebrafish appears to be inconsequential and possibly compensated for by a yet unknown mechanism.
28926587	5	79	theme	493-aa	942:947	arg1	proteins					949:956	493-aa proteins	942:956	493-aa proteins	942:956	The b3glcta and b3glctb genes encode for 496-aa and 493-aa proteins with 65% and 57% identity to human B3GLCT, respectively.
28926587	9	80	from	embryos	1570:1576	arg1	Extracts					1528:1535	Extracts	1528:1535	Extracts from double homozygous b3glct-/- embryos	1528:1576	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	7	81	theme	glucosylation	1155:1167	arg1	assays					1169:1174	In vitro glucosylation assays	1146:1174	In vitro glucosylation assays	1146:1174	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	2	82	theme	loss-of-function	385:400	arg1	mutations					402:410	loss-of-function mutations	385:410	loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs)	385:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	7	83	theme	In	1146:1147	arg1	assays					1169:1174	In vitro glucosylation assays	1146:1174	In vitro glucosylation assays	1146:1174	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	12	84	theme	B3GLCT/b3glct	1964:1976	arg1	genes					1978:1982	B3GLCT/b3glct genes	1964:1982	B3GLCT/b3glct genes	1964:1982	The presented data show that both sequence and function of B3GLCT/b3glct genes is conserved in vertebrates.
28926587	7	85	theme	O-fucosylated	1309:1321	arg1	TSR					1323:1325	an O-fucosylated TSR	1306:1325	an O-fucosylated TSR	1306:1325	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	11	86	theme	embryos	1763:1769	arg1	analyses					1708:1715	Transcriptome analyses	1694:1715	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos	1694:1769	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	0	87	theme	zebrafish	31:39	arg1	orthologs					41:49	zebrafish orthologs	31:49	zebrafish orthologs	31:49	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	1	88	theme	facial	279:284	arg1	features					286:293	characteristic facial features	264:293	characteristic facial features	264:293	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	9	89	theme	in	1608:1609	arg1	activity					1624:1631	in vitro b3glct activity	1608:1631	in vitro b3glct activity	1608:1631	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	6	90	theme	Expression	1015:1024	arg1	studies					1026:1032	Expression studies	1015:1032	Expression studies	1015:1032	Expression studies demonstrate that both orthologs are widely expressed with strong presence in embryonic tissues affected in PPS.
28926587	3	91	theme	non-canonical	637:649	arg1	mechanism					670:678	a non-canonical ER quality control mechanism	635:678	a non-canonical ER quality control mechanism	635:678	B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood.
28926587	2	92	theme	B3GLCT	419:424	arg1	gene					426:429	the B3GLCT gene	415:429	the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs)	415:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	9	93	theme	b3glct	1617:1622	arg1	activity					1624:1631	in vitro b3glct activity	1608:1631	in vitro b3glct activity	1608:1631	Extracts from double homozygous b3glct-/- embryos demonstrated complete loss of in vitro b3glct activity.
28926587	11	94	theme	trunk	1729:1733	arg1	tissues					1735:1741	head and trunk tissues	1720:1741	head and trunk tissues	1720:1741	Transcriptome analyses of head and trunk tissues of b3glct-/- 24-hpf embryos identified 483 shared differentially regulated transcripts that may be involved in compensation for b3glct function in these embryos.
28926587	0	95	theme	human	58:62	arg1	gene					98:101	the human Beta 3-Glucosyltransferase B3GLCT gene	54:101	the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome	54:133	Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome.
28926587	5	96	theme	human	987:991	arg1	B3GLCT					993:998	human B3GLCT	987:998	human B3GLCT	987:998	The b3glcta and b3glctb genes encode for 496-aa and 493-aa proteins with 65% and 57% identity to human B3GLCT, respectively.
28926587	1	97	theme	other	320:324	arg1	defects					351:357	other highly variable systemic defects	320:357	other highly variable systemic defects	320:357	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
28926587	7	98	theme	capable	1254:1260	arg1	enzyme					1247:1252	active b3glct enzyme	1233:1252	active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT	1233:1379	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	2	99	from	fucose	552:557	arg1	type					577:580	thrombospondin type 1 repeats (TSRs)	562:597	thrombospondin type 1 repeats (TSRs)	562:597	Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs).
28926587	3	100	theme	quality	654:660	arg1	mechanism					670:678	a non-canonical ER quality control mechanism	635:678	a non-canonical ER quality control mechanism	635:678	B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood.
28926587	13	101	theme	b3glct	2040:2045	arg1	deficiency					2047:2056	complete b3glct deficiency	2031:2056	complete b3glct deficiency in zebrafish	2031:2069	At the same time, complete b3glct deficiency in zebrafish appears to be inconsequential and possibly compensated for by a yet unknown mechanism.
28926587	7	102	theme	b3glct	1240:1245	arg1	enzyme					1247:1252	active b3glct enzyme	1233:1252	active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT	1233:1379	In vitro glucosylation assays demonstrated that extracts from wildtype embryos contain active b3glct enzyme capable of transferring glucose from UDP-glucose to an O-fucosylated TSR, indicating functional conservation with human B3GLCT.
28926587	8	103	theme	genes	1435:1439	arg1	role					1413:1416	the developmental role	1395:1416	the developmental role of the zebrafish genes	1395:1439	To determine the developmental role of the zebrafish genes, single and double b3glct knockouts were generated using TALEN-induced genome editing.
28926587	1	104	theme	short	234:238	arg1	stature					240:246	short stature	234:246	short stature	234:246	Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects.
29986387	1	0	theme	type	332:335	arg1	diabetes					340:347	type II diabetes	332:347	type II diabetes	332:347	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	7	1	from	imaging	1383:1389	arg1	cells					1424:1428	living MCF-7 cells	1411:1428	living MCF-7 cells	1411:1428	Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells.
29986387	5	2	theme	fluorescent	1083:1093	arg1	Cl₂					1123:1125	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5)	1079:1129	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions	1079:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	0	3	theme	Ac₄GlcNAc	68:76	arg1	Moiety					78:83	an Appended Ac₄GlcNAc Moiety	56:83	an Appended Ac₄GlcNAc Moiety	56:83	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	5	4	theme	₂	1106:1106	arg1	Cl₂					1123:1125	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5)	1079:1129	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions	1079:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	5	theme	neutral	1146:1152	arg1	conditions					1163:1172	mild and neutral reaction conditions	1137:1172	mild and neutral reaction conditions	1137:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	0	6	theme	Click	88:92	arg1	Reaction					94:101	Click Reaction	88:101	Click Reaction	88:101	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	2	7	from	proteins	444:451	arg1	cells					475:479	cells	475:479	cells	475:479	However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases.
29986387	6	8	theme	fluorescence	1220:1231	arg1	characteristics					1233:1247	fluorescence characteristics	1220:1247	fluorescence characteristics	1220:1247	Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells.
29986387	7	9	theme	transported	1396:1406	arg1	imaging					1383:1389	successful fluorescent imaging	1360:1389	successful fluorescent imaging of 5 transported in living MCF-7 cells	1360:1428	Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells.
29986387	4	10	theme	microscopic	774:784	arg1	inspection					786:795	intra-cellular microscopic inspection	759:795	intra-cellular microscopic inspection	759:795	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	5	11	theme	reaction	1154:1161	arg1	conditions					1163:1172	mild and neutral reaction conditions	1137:1172	mild and neutral reaction conditions	1137:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	7	12	theme	fluorescent	1371:1381	arg1	imaging					1383:1389	successful fluorescent imaging	1360:1389	successful fluorescent imaging of 5 transported in living MCF-7 cells	1360:1428	Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells.
29986387	2	13	from	function	463:470	arg1	cells					475:479	cells	475:479	cells	475:479	However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases.
29986387	4	14	theme	fluorescent	711:721	arg1	tag					723:725	fluorescent tag	711:725	fluorescent tag	711:725	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	3	15	theme	powerful	543:550	arg1	microscopy					527:536	Confocal microscopy	518:536	Confocal microscopy	518:536	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	3	15	theme	powerful	543:550	arg1	tool					566:569	a powerful and effective tool	541:569	a powerful and effective tool for in-cell elucidation of the function of biological molecules	541:633	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	6	16	theme	MCF-7	1316:1320	arg1	cells					1322:1326	sensitive MCF-7 cells	1306:1326	sensitive MCF-7 cells	1306:1326	Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells.
29986387	1	17	theme	Alzheimer’s	350:360	arg1	disease					362:368	Alzheimer’s disease	350:368	Alzheimer’s disease	350:368	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	2	18	theme	precise	400:406	arg1	undefined					492:500	undefined	492:500	undefined	492:500	However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases.
29986387	2	18	theme	precise	400:406	arg1	connexion					408:416	the precise connexion	396:416	the precise connexion between O-GlcNAc-modified proteins and their function in cells	396:479	However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases.
29986387	5	19	theme	corresponding	1006:1018	arg1	₂					1043:1043	the corresponding fluorescent tag Ru(bpy)₂	1002:1043	the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)	1002:1056	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	19	theme	corresponding	1006:1018	arg1	Phen-alkyne					1045:1055	Phen-alkyne	1045:1055	Phen-alkyne	1045:1055	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	4	20	theme	carbohydrates	692:704	arg1	labeling					645:652	Chemical labeling	636:652	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag	636:725	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	4	20	theme	carbohydrates	692:704	arg1	step					743:746	an essential step	730:746	an essential step that makes intra-cellular microscopic inspection possible	730:804	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	2	21	theme	most	506:509	arg1	cases					511:515	most cases	506:515	most cases	506:515	However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases.
29986387	5	22	theme	Ru	1099:1100	arg1	Cl₂					1123:1125	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5)	1079:1129	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions	1079:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	6	23	theme	sensitive	1306:1314	arg1	cells					1322:1326	sensitive MCF-7 cells	1306:1326	sensitive MCF-7 cells	1306:1326	Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells.
29986387	5	24	theme	fluorescent	1020:1030	arg1	₂					1043:1043	the corresponding fluorescent tag Ru(bpy)₂	1002:1043	the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)	1002:1056	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	24	theme	fluorescent	1020:1030	arg1	Phen-alkyne					1045:1055	Phen-alkyne	1045:1055	Phen-alkyne	1045:1055	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	1	25	theme	abundant	169:176	arg1	modification					197:208	an abundant post-translational modification	166:208	an abundant post-translational modification	166:208	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	1	25	theme	abundant	169:176	arg1	modification					150:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	5	26	theme	Ru	1036:1037	arg1	₂					1043:1043	the corresponding fluorescent tag Ru(bpy)₂	1002:1043	the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)	1002:1056	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	26	theme	Ru	1036:1037	arg1	Phen-alkyne					1045:1055	Phen-alkyne	1045:1055	Phen-alkyne	1045:1055	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	7	27	theme	MCF-7	1418:1422	arg1	cells					1424:1428	living MCF-7 cells	1411:1428	living MCF-7 cells	1411:1428	Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells.
29986387	6	28	theme	good	1194:1197	arg1	stability					1199:1207	good stability	1194:1207	good stability	1194:1207	Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells.
29986387	4	29	theme	intra-cellular	759:772	arg1	inspection					786:795	intra-cellular microscopic inspection	759:795	intra-cellular microscopic inspection	759:795	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	5	30	theme	dye	1095:1097	arg1	Cl₂					1123:1125	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5)	1079:1129	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions	1079:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	1	31	theme	post-translational	178:195	arg1	modification					197:208	an abundant post-translational modification	166:208	an abundant post-translational modification	166:208	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	1	31	theme	post-translational	178:195	arg1	modification					150:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	5	32	theme	azido	985:989	arg1	group					991:995	an azido group	982:995	an azido group	982:995	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	6	33	theme	cytotoxicity	1285:1296	arg1	levels					1275:1280	rather low levels	1264:1280	rather low levels of cytotoxicity	1264:1296	Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells.
29986387	4	34	theme	non-fluorescent	676:690	arg1	carbohydrates					692:704	non-ultraviolet or non-fluorescent carbohydrates	657:704	non-ultraviolet or non-fluorescent carbohydrates	657:704	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	0	35	theme	Novel	15:19	arg1	Complex					43:49	a Novel Fluorescent Ruthenium Complex	13:49	a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety	13:83	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	1	36	theme	many	281:284	arg1	cells					286:290	many cells	281:290	many cells	281:290	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	4	37	theme	Chemical	636:643	arg1	labeling					645:652	Chemical labeling	636:652	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag	636:725	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	4	37	theme	Chemical	636:643	arg1	step					743:746	an essential step	730:746	an essential step that makes intra-cellular microscopic inspection possible	730:804	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	0	38	with	Complex	43:49	arg1	Moiety					78:83	an Appended Ac₄GlcNAc Moiety	56:83	an Appended Ac₄GlcNAc Moiety	56:83	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	1	39	theme	cells	286:290	arg1	activity					269:276	the activity	265:276	the activity of many cells	265:290	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	5	40	dep	Ac₄GlcNAc	954:962	arg1	substituted					965:975	substituted	965:975	substituted with an azido group	965:995	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	3	41	theme	effective	556:564	arg1	microscopy					527:536	Confocal microscopy	518:536	Confocal microscopy	518:536	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	3	41	theme	effective	556:564	arg1	tool					566:569	a powerful and effective tool	541:569	a powerful and effective tool for in-cell elucidation of the function of biological molecules	541:633	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	1	42	theme	eukaryotic	213:222	arg1	cells					224:228	eukaryotic cells	213:228	eukaryotic cells	213:228	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	0	43	theme	Ruthenium	33:41	arg1	Complex					43:49	a Novel Fluorescent Ruthenium Complex	13:49	a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety	13:83	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	5	44	theme	mild	1137:1140	arg1	conditions					1163:1172	mild and neutral reaction conditions	1137:1172	mild and neutral reaction conditions	1137:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	45	theme	N-acetylglucosamine	915:933	arg1	analogues					944:952	unnatural N-acetylglucosamine (GlcNAc) analogues	905:952	unnatural N-acetylglucosamine (GlcNAc) analogues	905:952	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	46	theme	click	880:884	arg1	chemistry					886:894	click chemistry	880:894	click chemistry	880:894	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	0	47	theme	Fluorescent	21:31	arg1	Complex					43:49	a Novel Fluorescent Ruthenium Complex	13:49	a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety	13:83	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	5	48	theme	Phen-Ac₄GlcNAc	1108:1121	arg1	Cl₂					1123:1125	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5)	1079:1129	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions	1079:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	49	theme	unnatural	905:913	arg1	GlcNAc					936:941	GlcNAc	936:941	GlcNAc	936:941	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	49	theme	unnatural	905:913	arg1	N-acetylglucosamine					915:933	unnatural N-acetylglucosamine	905:933	unnatural N-acetylglucosamine (GlcNAc) analogues	905:952	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	2	50	theme	O-GlcNAc-modified	426:442	arg1	proteins					444:451	O-GlcNAc-modified proteins	426:451	O-GlcNAc-modified proteins	426:451	However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases.
29986387	5	51	theme	1,3-dipolar	846:856	arg1	cycloaddition					858:870	the 1,3-dipolar cycloaddition	842:870	the 1,3-dipolar cycloaddition	842:870	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	6	52	theme	low	1271:1273	arg1	levels					1275:1280	rather low levels	1264:1280	rather low levels of cytotoxicity	1264:1296	Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells.
29986387	3	53	theme	in-cell	575:581	arg1	elucidation					583:593	in-cell elucidation	575:593	in-cell elucidation of the function of biological molecules	575:633	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	7	54	theme	living	1411:1416	arg1	cells					1424:1428	living MCF-7 cells	1411:1428	living MCF-7 cells	1411:1428	Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells.
29986387	4	55	theme	essential	733:741	arg1	labeling					645:652	Chemical labeling	636:652	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag	636:725	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	4	55	theme	essential	733:741	arg1	step					743:746	an essential step	730:746	an essential step that makes intra-cellular microscopic inspection possible	730:804	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	0	56	theme	Complex	43:49	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction	0:101	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	8	57	theme	Cell	1431:1434	arg1	images					1436:1441	Cell images	1431:1441	Cell images	1431:1441	Cell images displayed that proteins are potentially labelled with 5 in the cytoplasm.
29986387	1	58	theme	O-linked	108:115	arg1	modification					197:208	an abundant post-translational modification	166:208	an abundant post-translational modification	166:208	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	1	58	theme	O-linked	108:115	arg1	modification					150:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	4	59	with	labeling	645:652	arg1	tag					723:725	fluorescent tag	711:725	fluorescent tag	711:725	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	3	60	theme	biological	614:623	arg1	molecules					625:633	biological molecules	614:633	biological molecules	614:633	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	5	61	theme	₂	1043:1043	arg1	Cl₂					1057:1059	Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4)	954:1063	Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4)	954:1063	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	1	62	theme	β-N-acetylglucosamine	117:137	arg1	modification					197:208	an abundant post-translational modification	166:208	an abundant post-translational modification	166:208	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	1	62	theme	β-N-acetylglucosamine	117:137	arg1	modification					150:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	7	63	theme	successful	1360:1369	arg1	imaging					1383:1389	successful fluorescent imaging	1360:1389	successful fluorescent imaging of 5 transported in living MCF-7 cells	1360:1428	Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells.
29986387	1	64	link	O-linked	108:115	arg1	modification					197:208	an abundant post-translational modification	166:208	an abundant post-translational modification	166:208	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	1	64	link	O-linked	108:115	arg1	modification					150:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	5	65	theme	Ac₄GlcNAc	954:962	arg1	Cl₂					1057:1059	Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4)	954:1063	Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4)	954:1063	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	3	66	theme	molecules	625:633	arg1	function					602:609	the function	598:609	the function of biological molecules	598:633	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	0	67	theme	Appended	59:66	arg1	Moiety					78:83	an Appended Ac₄GlcNAc Moiety	56:83	an Appended Ac₄GlcNAc Moiety	56:83	Synthesis of a Novel Fluorescent Ruthenium Complex with an Appended Ac₄GlcNAc Moiety by Click Reaction.
29986387	3	68	theme	function	602:609	arg1	elucidation					583:593	in-cell elucidation	575:593	in-cell elucidation of the function of biological molecules	575:633	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	1	69	from	modification	197:208	arg1	cells					224:228	eukaryotic cells	213:228	eukaryotic cells	213:228	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	1	70	theme	O-GlcNAc	140:147	arg1	modification					197:208	an abundant post-translational modification	166:208	an abundant post-translational modification	166:208	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	1	70	theme	O-GlcNAc	140:147	arg1	modification					150:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	104:161	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29986387	4	71	theme	non-ultraviolet	657:671	arg1	carbohydrates					692:704	non-ultraviolet or non-fluorescent carbohydrates	657:704	non-ultraviolet or non-fluorescent carbohydrates	657:704	Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible.
29986387	5	72	theme	tag	1032:1034	arg1	₂					1043:1043	the corresponding fluorescent tag Ru(bpy)₂	1002:1043	the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)	1002:1056	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	72	theme	tag	1032:1034	arg1	Phen-alkyne					1045:1055	Phen-alkyne	1045:1055	Phen-alkyne	1045:1055	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	73	theme	bpy	1102:1104	arg1	Cl₂					1123:1125	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5)	1079:1129	the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions	1079:1172	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	74	theme	bpy	1039:1041	arg1	₂					1043:1043	the corresponding fluorescent tag Ru(bpy)₂	1002:1043	the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)	1002:1056	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	5	74	theme	bpy	1039:1041	arg1	Phen-alkyne					1045:1055	Phen-alkyne	1045:1055	Phen-alkyne	1045:1055	Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac₄GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)₂(Phen-alkyne)Cl₂ (4) to synthesize the fluorescent dye Ru(bpy)₂(Phen-Ac₄GlcNAc)Cl₂ (5) under mild and neutral reaction conditions.
29986387	3	75	theme	Confocal	518:525	arg1	microscopy					527:536	Confocal microscopy	518:536	Confocal microscopy	518:536	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	3	75	theme	Confocal	518:525	arg1	tool					566:569	a powerful and effective tool	541:569	a powerful and effective tool for in-cell elucidation of the function of biological molecules	541:633	Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules.
29986387	1	76	theme	fundamental	245:255	arg1	role					257:260	a fundamental role	243:260	a fundamental role	243:260	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers.
29941542	8	0	theme	regulatory	1411:1420	arg1	mechanisms					1422:1431	key regulatory mechanisms	1407:1431	key regulatory mechanisms	1407:1431	Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.
29941542	5	1	from	transplantation	891:905	arg1	mice					910:913	mice	910:913	mice	910:913	Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis.
29941542	4	2	theme	OGT	718:720	arg1	Deletion					706:713	Deletion	706:713	Deletion of OGT specifically in IECs	706:741	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	1	3	from	modifications	104:116	arg1	IECs					150:153	IECs	150:153	IECs	150:153	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	1	3	from	modifications	104:116	arg1	cells					143:147	intestinal epithelial cells	121:147	intestinal epithelial cells (IECs)	121:154	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	6	4	theme	cell-specific	1067:1079	arg1	deletion					1081:1088	Paneth cell-specific deletion	1060:1088	Paneth cell-specific deletion of OGT	1060:1095	Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis.
29941542	5	5	theme	spontaneous	993:1003	arg1	inflammation					1005:1016	spontaneous inflammation	993:1016	spontaneous inflammation	993:1016	Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis.
29941542	7	6	theme	other	1193:1197	arg1	hand					1199:1202	the other hand	1189:1202	the other hand	1189:1202	On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis.
29941542	1	7	from	control	174:180	arg1	homeostasis					196:206	intestinal homeostasis	185:206	intestinal homeostasis	185:206	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	3	8	theme	protein	549:555	arg1	O-GlcNAcylation					557:571	protein O-GlcNAcylation	549:571	protein O-GlcNAcylation	549:571	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	4	9	from	Deletion	706:713	arg1	IECs					738:741	IECs	738:741	IECs	738:741	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	0	10	from	Deficiency	0:9	arg1	O-GlcNAcylation					36:50	intestinal epithelial O-GlcNAcylation	14:50	intestinal epithelial O-GlcNAcylation	14:50	Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.
29941542	4	11	from	dysbiosis	795:803	arg1	mice					862:865	mice	862:865	mice	862:865	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	2	12	dep	controls	405:412	arg1	unexplored					507:516	unexplored	507:516	are still largely unexplored	489:516	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	4	13	theme	epithelial	765:774	arg1	barrier					776:782	disrupted epithelial barrier	755:782	disrupted epithelial barrier	755:782	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	4	14	theme	disrupted	755:763	arg1	barrier					776:782	disrupted epithelial barrier	755:782	disrupted epithelial barrier	755:782	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	3	15	theme	transferase	604:614	arg1	levels					539:544	levels	539:544	levels of protein O-GlcNAcylation	539:571	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	3	15	theme	transferase	604:614	arg1	expression					581:590	the expression	577:590	the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety,	577:660	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	7	16	theme	chemical-induced	1319:1334	arg1	colitis					1336:1342	chemical-induced colitis	1319:1342	chemical-induced colitis	1319:1342	On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis.
29941542	3	17	theme	O-GlcNAc	595:602	arg1	enzyme					627:632	the enzyme	623:632	the enzyme adding the O-GlcNAc moiety	623:659	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	3	17	theme	O-GlcNAc	595:602	arg1	OGT					617:619	OGT	617:619	OGT	617:619	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	3	17	theme	O-GlcNAc	595:602	arg1	transferase					604:614	O-GlcNAc transferase	595:614	O-GlcNAc transferase (OGT)	595:620	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	1	18	theme	inflammatory	292:303	arg1	disease					311:317	inflammatory bowel disease	292:317	inflammatory bowel disease	292:317	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	5	19	theme	microbial	937:945	arg1	dysbiosis					947:955	that microbial dysbiosis	932:955	that microbial dysbiosis	932:955	Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis.
29941542	7	20	theme	O-GlcNAc	1225:1232	arg1	signaling					1234:1242	O-GlcNAc signaling	1225:1242	O-GlcNAc signaling	1225:1242	On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis.
29941542	6	21	theme	cell	1111:1114	arg1	dysfunction					1116:1126	Paneth cell dysfunction	1104:1126	Paneth cell dysfunction	1104:1126	Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis.
29941542	1	22	theme	Post-translational	85:102	arg1	modifications					104:116	Post-translational modifications	85:116	Post-translational modifications in intestinal epithelial cells (IECs)	85:154	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	1	23	theme	intestinal	185:194	arg1	homeostasis					196:206	intestinal homeostasis	185:206	intestinal homeostasis	185:206	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	6	24	theme	chemical-induced	1160:1175	arg1	colitis					1177:1183	chemical-induced colitis	1160:1183	chemical-induced colitis	1160:1183	Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis.
29941542	4	25	from	barrier	776:782	arg1	mice					862:865	mice	862:865	mice	862:865	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	5	26	theme	chemical-induced	1034:1049	arg1	colitis					1051:1057	exacerbated chemical-induced colitis	1022:1057	exacerbated chemical-induced colitis	1022:1057	Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis.
29941542	1	27	theme	homeostasis	196:206	arg1	breakdown					213:221	the breakdown	209:221	the breakdown	209:221	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	7	28	theme	signaling	1234:1242	arg1	augmentation					1209:1220	the augmentation	1205:1220	the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation,	1205:1306	On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis.
29941542	2	29	theme	O-GlcNAc	356:363	arg1	modification					366:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	320:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins	320:403	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	1	30	theme	bowel	305:309	arg1	disease					311:317	inflammatory bowel disease	292:317	inflammatory bowel disease	292:317	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	1	31	theme	intestinal	121:130	arg1	IECs					150:153	IECs	150:153	IECs	150:153	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	1	31	theme	intestinal	121:130	arg1	cells					143:147	intestinal epithelial cells	121:147	intestinal epithelial cells (IECs)	121:154	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	4	32	theme	microbial	785:793	arg1	dysbiosis					795:803	microbial dysbiosis	785:803	microbial dysbiosis	785:803	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	0	33	theme	epithelial	25:34	arg1	O-GlcNAcylation					36:50	intestinal epithelial O-GlcNAcylation	14:50	intestinal epithelial O-GlcNAcylation	14:50	Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.
29941542	8	34	from	O-GlcNAcylation	1374:1388	arg1	IECs					1393:1396	IECs	1393:1396	IECs	1393:1396	Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.
29941542	2	35	theme	β-N-acetylglucosamine	333:353	arg1	modification					366:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	320:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins	320:403	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	2	36	from	modification	366:377	arg1	proteins					396:403	intracellular proteins	382:403	intracellular proteins	382:403	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	2	37	theme	intestinal	466:475	arg1	homeostasis					477:487	intestinal homeostasis	466:487	intestinal homeostasis	466:487	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	0	38	theme	intestinal	14:23	arg1	O-GlcNAcylation					36:50	intestinal epithelial O-GlcNAcylation	14:50	intestinal epithelial O-GlcNAcylation	14:50	Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.
29941542	5	39	theme	exacerbated	1022:1032	arg1	colitis					1051:1057	exacerbated chemical-induced colitis	1022:1057	exacerbated chemical-induced colitis	1022:1057	Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis.
29941542	2	40	theme	O-linked	324:331	arg1	modification					366:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	320:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins	320:403	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	3	41	theme	O-GlcNAcylation	557:571	arg1	levels					539:544	levels	539:544	levels of protein O-GlcNAcylation	539:571	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	3	41	theme	O-GlcNAcylation	557:571	arg1	expression					581:590	the expression	577:590	the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety,	577:660	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	1	42	dep	damage	265:270	arg1	the					248:250	the	248:250	the	248:250	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	4	43	theme	intestinal	835:844	arg1	inflammation					846:857	intestinal inflammation	835:857	intestinal inflammation in mice	835:865	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	6	44	theme	Paneth	1104:1109	arg1	dysfunction					1116:1126	Paneth cell dysfunction	1104:1126	Paneth cell dysfunction	1104:1126	Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis.
29941542	5	45	theme	microbiota	880:889	arg1	transplantation					891:905	fecal microbiota transplantation	874:905	fecal microbiota transplantation in mice	874:913	Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis.
29941542	1	46	from	inflammation	276:287	arg1	disease					311:317	inflammatory bowel disease	292:317	inflammatory bowel disease	292:317	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	5	47	theme	fecal	874:878	arg1	transplantation					891:905	fecal microbiota transplantation	874:905	fecal microbiota transplantation in mice	874:913	Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis.
29941542	0	48	theme	gut	67:69	arg1	inflammation					71:82	gut inflammation	67:82	gut inflammation	67:82	Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.
29941542	2	49	link	O-linked	324:331	arg1	modification					366:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification	320:377	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins	320:403	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	4	50	from	inflammation	846:857	arg1	mice					862:865	mice	862:865	mice	862:865	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	2	51	theme	intracellular	382:394	arg1	proteins					396:403	intracellular proteins	382:403	intracellular proteins	382:403	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	1	52	from	damage	265:270	arg1	disease					311:317	inflammatory bowel disease	292:317	inflammatory bowel disease	292:317	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	3	53	theme	IBD	692:694	arg1	patients					696:703	human IBD patients	686:703	human IBD patients	686:703	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	8	54	theme	protein	1366:1372	arg1	O-GlcNAcylation					1374:1388	protein O-GlcNAcylation	1366:1388	protein O-GlcNAcylation in IECs	1366:1396	Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.
29941542	8	55	theme	key	1407:1409	arg1	mechanisms					1422:1431	key regulatory mechanisms	1407:1431	key regulatory mechanisms	1407:1431	Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.
29941542	4	56	theme	cell	813:816	arg1	dysfunction					818:828	Paneth cell dysfunction	806:828	Paneth cell dysfunction	806:828	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	1	57	theme	epithelial	132:141	arg1	IECs					150:153	IECs	150:153	IECs	150:153	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	1	57	theme	epithelial	132:141	arg1	cells					143:147	intestinal epithelial cells	121:147	intestinal epithelial cells (IECs)	121:154	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	8	58	theme	mucosal	1445:1451	arg1	homeostasis					1453:1463	mucosal homeostasis	1445:1463	mucosal homeostasis	1445:1463	Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.
29941542	4	59	theme	Paneth	806:811	arg1	dysfunction					818:828	Paneth cell dysfunction	806:828	Paneth cell dysfunction	806:828	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	2	60	from	roles	457:461	arg1	homeostasis					477:487	intestinal homeostasis	466:487	intestinal homeostasis	466:487	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	1	61	theme	precise	166:172	arg1	control					174:180	precise control	166:180	precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease	166:317	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	6	62	theme	OGT	1093:1095	arg1	deletion					1081:1088	Paneth cell-specific deletion	1060:1088	Paneth cell-specific deletion of OGT	1060:1095	Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis.
29941542	3	63	theme	human	686:690	arg1	patients					696:703	human IBD patients	686:703	human IBD patients	686:703	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	4	64	from	dysfunction	818:828	arg1	mice					862:865	mice	862:865	mice	862:865	Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice.
29941542	2	65	theme	biological	422:431	arg1	processes					433:441	diverse biological processes	414:441	diverse biological processes	414:441	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29941542	1	66	theme	pathological	252:263	arg1	damage					265:270	pathological damage	252:270	pathological damage	252:270	Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease.
29941542	3	67	theme	O-GlcNAc	645:652	arg1	moiety					654:659	the O-GlcNAc moiety	641:659	the O-GlcNAc moiety	641:659	Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients.
29941542	2	68	theme	diverse	414:420	arg1	processes					433:441	diverse biological processes	414:441	diverse biological processes	414:441	The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored.
29902539	4	0	with	glycoprotein	701:712	arg1	ability					754:760	pore-forming ability	741:760	pore-forming ability	741:760	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	4	1	theme	≈65 kDa	727:733	arg1	subunits					715:722	subunits	715:722	subunits of ≈65 kDa	715:733	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	10	2	theme	cholesterol	1670:1680	arg1	doses					1661:1665	increasing doses	1650:1665	increasing doses of cholesterol	1650:1680	In addition, we observed that the hemolytic activity was inhibited by increasing doses of cholesterol.
29902539	8	3	link	linked	1227:1232	arg1	residues					1250:1257	O- linked glycoconjugated residues	1224:1257	O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes)	1224:1359	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	3	link	linked	1227:1232	arg1	N-acetylglucosamine					1276:1294	galactose (1-4) N-acetylglucosamine	1260:1294	galactose (1-4) N-acetylglucosamine	1260:1294	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	3	link	linked	1227:1232	arg1	acid					1307:1310	sialic acid	1300:1310	sialic acid (2-3)	1300:1316	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	3	4	from	venom	638:642	arg1	component					587:595	the major bioactive component	567:595	the major bioactive component from the scorpionfish Scorpaena plumieri venom	567:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	3	4	from	venom	638:642	arg1	Sp-CTx					559:564	Sp-CTx	559:564	Sp-CTx	559:564	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	6	5	attach	presence	945:952	arg1	solution					982:989	a pH 7.4 solution	973:989	a pH 7.4 solution	973:989	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	6	5	attach	presence	945:952	arg2	glycerol					957:964	glycerol	957:964	glycerol 10%	957:968	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	8	6	from	acid	1307:1310	arg1	O-glycan					1341:1348	O-glycan	1341:1348	O-glycan	1341:1348	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	6	from	acid	1307:1310	arg1	N-					1331:1332	N-	1331:1332	N-	1331:1332	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	7	dep	N-acetylglucosamine	1276:1294	arg1	galactose					1318:1326	galactose	1318:1326	galactose	1318:1326	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	4	8	theme	hemolytic	662:670	arg1	glycoprotein					701:712	a large dimeric glycoprotein	685:712	a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability	685:760	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	4	8	theme	hemolytic	662:670	arg1	cytolysin					672:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	7	9	theme	hemolytic	1021:1029	arg1	activity					1031:1038	the hemolytic activity	1017:1038	the hemolytic activity of Sp-CTx	1017:1048	It was demonstrated that the hemolytic activity of Sp-CTx is calcium dependent, being abolished by EDTA and zinc ions.
29902539	7	9	theme	hemolytic	1021:1029	arg1	dependent					1061:1069	dependent	1061:1069	dependent	1061:1069	It was demonstrated that the hemolytic activity of Sp-CTx is calcium dependent, being abolished by EDTA and zinc ions.
29902539	13	10	theme	lipid-dependent	2214:2228	arg1	formation					2235:2243	lipid-dependent pore formation	2214:2243	lipid-dependent pore formation	2214:2243	Taken together, our results could suggest that, as has been already reported for other fish cytolysins, Sp-CTx acts mostly through lipid-dependent pore formation not only in erythrocytes but also in other cell types, which could account for the pain observed upon envenomation.
29902539	4	11	gly	glycoprotein	701:712	arg1	glycoprotein					701:712	a large dimeric glycoprotein	685:712	a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability	685:760	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	4	11	gly	glycoprotein	701:712	arg1	cytolysin					672:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	3	12	theme	storage	536:542	arg1	conditions					544:553	optimal storage conditions	528:553	optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom	528:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	3	13	theme	major	571:575	arg1	component					587:595	the major bioactive component	567:595	the major bioactive component from the scorpionfish Scorpaena plumieri venom	567:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	3	13	theme	major	571:575	arg1	Sp-CTx					559:564	Sp-CTx	559:564	Sp-CTx	559:564	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	8	14	dep	residues	1250:1257	arg1	residues					1250:1257	O- linked glycoconjugated residues	1224:1257	O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes)	1224:1359	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	14	dep	residues	1250:1257	arg1	2-3					1313:1315	2-3	1313:1315	2-3	1313:1315	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	14	dep	residues	1250:1257	arg1	N-acetylglucosamine					1276:1294	galactose (1-4) N-acetylglucosamine	1260:1294	galactose (1-4) N-acetylglucosamine	1260:1294	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	14	dep	residues	1250:1257	arg1	acid					1307:1310	sialic acid	1300:1310	sialic acid (2-3)	1300:1316	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	15	theme	maximal	1148:1154	arg1	activity					1166:1173	its maximal hemolytic activity	1144:1173	its maximal hemolytic activity	1144:1173	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	12	16	with	pre-treatment	1892:1904	arg1	aprotinin					1911:1919	aprotinin	1911:1919	aprotinin	1911:1919	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	12	16	with	pre-treatment	1892:1904	arg1	HOE-140					1925:1931	HOE-140	1925:1931	HOE-140	1925:1931	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	9	17	theme	Sp-CTx	1388:1393	arg1	activity					1376:1383	The hemolytic activity	1362:1383	The hemolytic activity of Sp-CTx	1362:1393	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	12	18	theme	kallikrein-kinin	1969:1984	arg1	system					1986:1991	the kallikrein-kinin system	1965:1991	the kallikrein-kinin system	1965:1991	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	13	19	theme	cell	2288:2291	arg1	types					2293:2297	other cell types	2282:2297	other cell types	2282:2297	Taken together, our results could suggest that, as has been already reported for other fish cytolysins, Sp-CTx acts mostly through lipid-dependent pore formation not only in erythrocytes but also in other cell types, which could account for the pain observed upon envenomation.
29902539	1	20	theme	hemolytic	115:123	arg1	activity					125:132	the hemolytic activity	111:132	the hemolytic activity found in scorpaeniform fish venoms	111:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	14	21	theme	cytolysins	2454:2463	arg1	characterization					2429:2444	the complete characterization	2416:2444	the complete characterization of fish cytolysins	2416:2463	We believe that the present work paves the way towards the complete characterization of fish cytolysins.
29902539	0	22	theme	cytolytic	59:67	arg1	Sp-CTx					76:81	Sp-CTx	76:81	Sp-CTx	76:81	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	0	22	theme	cytolytic	59:67	arg1	toxin					69:73	the Scorpaena plumieri cytolytic toxin	36:73	the Scorpaena plumieri cytolytic toxin (Sp-CTx)	36:82	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	6	23	theme	10	966:967	arg1	%					968:968	%	968:968	%	968:968	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	8	24	theme	glycoconjugated	1234:1248	arg1	residues					1250:1257	O- linked glycoconjugated residues	1224:1257	O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes)	1224:1359	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	24	theme	glycoconjugated	1234:1248	arg1	N-acetylglucosamine					1276:1294	galactose (1-4) N-acetylglucosamine	1260:1294	galactose (1-4) N-acetylglucosamine	1260:1294	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	24	theme	glycoconjugated	1234:1248	arg1	acid					1307:1310	sialic acid	1300:1310	sialic acid (2-3)	1300:1316	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	1	25	theme	scorpaeniform	143:155	arg1	venoms					162:167	scorpaeniform fish venoms	143:167	scorpaeniform fish venoms	143:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	14	26	theme	complete	2420:2427	arg1	characterization					2429:2444	the complete characterization	2416:2444	the complete characterization of fish cytolysins	2416:2463	We believe that the present work paves the way towards the complete characterization of fish cytolysins.
29902539	0	27	from	Advances	0:7	arg1	characterization					16:31	the characterization	12:31	the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx)	12:82	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	1	28	located	found	134:138	arg1	venoms					162:167	scorpaeniform fish venoms	143:167	scorpaeniform fish venoms	143:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	1	28	located	found	134:138	arg2	activity					125:132	the hemolytic activity	111:132	the hemolytic activity found in scorpaeniform fish venoms	111:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	13	29	theme	other	2164:2168	arg1	cytolysins					2175:2184	other fish cytolysins	2164:2184	other fish cytolysins	2164:2184	Taken together, our results could suggest that, as has been already reported for other fish cytolysins, Sp-CTx acts mostly through lipid-dependent pore formation not only in erythrocytes but also in other cell types, which could account for the pain observed upon envenomation.
29902539	6	30	from	presence	945:952	arg1	solution					982:989	a pH 7.4 solution	973:989	a pH 7.4 solution	973:989	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	9	31	theme	direct	1476:1481	arg1	interaction					1497:1507	a direct electrostatic interaction lipid - toxin	1474:1521	a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin	1474:1577	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	5	32	dep	60	869:870	arg1	to					866:867	to	866:867	to	866:867	We were able to establish storage conditions that allowed us to keep the toxin partially active for up to 60 days.
29902539	13	33	theme	other	2282:2286	arg1	types					2293:2297	other cell types	2282:2297	other cell types	2282:2297	Taken together, our results could suggest that, as has been already reported for other fish cytolysins, Sp-CTx acts mostly through lipid-dependent pore formation not only in erythrocytes but also in other cell types, which could account for the pain observed upon envenomation.
29902539	2	34	theme	protein	352:358	arg1	factors					367:373	protein lethal factors	352:373	protein lethal factors	352:373	These multifunctional toxins, described as protein lethal factors and referred to as cytolysins, are known to be extremely labile molecules.
29902539	12	35	theme	toxin-induced	2056:2068	arg1	nociception					2070:2080	the toxin-induced nociception	2052:2080	the toxin-induced nociception	2052:2080	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	8	36	dep	linked	1227:1232	arg1	O-					1224:1225	O-	1224:1225	O-	1224:1225	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	6	37	theme	pH	975:976	arg1	solution					982:989	a pH 7.4 solution	973:989	a pH 7.4 solution	973:989	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	3	38	theme	Scorpaena	619:627	arg1	venom					638:642	the scorpionfish Scorpaena plumieri venom	602:642	the scorpionfish Scorpaena plumieri venom	602:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	0	39	theme	Scorpaena	40:48	arg1	Sp-CTx					76:81	Sp-CTx	76:81	Sp-CTx	76:81	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	0	39	theme	Scorpaena	40:48	arg1	toxin					69:73	the Scorpaena plumieri cytolytic toxin	36:73	the Scorpaena plumieri cytolytic toxin (Sp-CTx)	36:82	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	14	40	theme	present	2381:2387	arg1	work					2389:2392	the present work	2377:2392	the present work	2377:2392	We believe that the present work paves the way towards the complete characterization of fish cytolysins.
29902539	9	41	theme	pore-formation	1530:1543	arg1	mechanism					1545:1553	the pore-formation mechanism	1526:1553	the pore-formation mechanism of action of this toxin	1526:1577	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	12	42	theme	significant	2030:2040	arg1	effect					2042:2047	no significant effect	2027:2047	no significant effect	2027:2047	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	11	43	dep	pain	1784:1787	arg1	the					1780:1782	the	1780:1782	the	1780:1782	Finally, we were able to show, for first time, that Sp-CTx is at least partially responsible for the pain and inflammation observed upon envenomation.
29902539	2	44	theme	multifunctional	315:329	arg1	toxins					331:336	These multifunctional toxins	309:336	These multifunctional toxins	309:336	These multifunctional toxins, described as protein lethal factors and referred to as cytolysins, are known to be extremely labile molecules.
29902539	10	45	theme	increasing	1650:1659	arg1	doses					1661:1665	increasing doses	1650:1665	increasing doses of cholesterol	1650:1680	In addition, we observed that the hemolytic activity was inhibited by increasing doses of cholesterol.
29902539	8	46	from	N-acetylglucosamine	1276:1294	arg1	O-glycan					1341:1348	O-glycan	1341:1348	O-glycan	1341:1348	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	46	from	N-acetylglucosamine	1276:1294	arg1	N-					1331:1332	N-	1331:1332	N-	1331:1332	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	9	47	theme	toxin	1573:1577	arg1	action					1558:1563	action	1558:1563	action of this toxin	1558:1577	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	7	48	theme	Sp-CTx	1043:1048	arg1	activity					1031:1038	the hemolytic activity	1017:1038	the hemolytic activity of Sp-CTx	1017:1048	It was demonstrated that the hemolytic activity of Sp-CTx is calcium dependent, being abolished by EDTA and zinc ions.
29902539	7	48	theme	Sp-CTx	1043:1048	arg1	dependent					1061:1069	dependent	1061:1069	dependent	1061:1069	It was demonstrated that the hemolytic activity of Sp-CTx is calcium dependent, being abolished by EDTA and zinc ions.
29902539	1	49	dep	responsible	173:183	arg1	Proteins					85:92	Proteins	85:92	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms	85:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	1	49	dep	responsible	173:183	arg1	effects					300:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	4	50	theme	large	687:691	arg1	glycoprotein					701:712	a large dimeric glycoprotein	685:712	a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability	685:760	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	4	50	theme	large	687:691	arg1	cytolysin					672:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	1	51	theme	fish	157:160	arg1	venoms					162:167	scorpaeniform fish venoms	143:167	scorpaeniform fish venoms	143:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	12	52	contain	had	2023:2025	arg1	drugs					2017:2021	these drugs	2011:2021	these drugs	2011:2021	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	12	52	contain	had	2023:2025	arg2	effect					2042:2047	no significant effect	2027:2047	no significant effect	2027:2047	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	8	53	theme	hemolytic	1156:1164	arg1	activity					1166:1173	its maximal hemolytic activity	1144:1173	its maximal hemolytic activity	1144:1173	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	5	54	theme	active	852:857	arg1	toxin					836:840	the toxin	832:840	the toxin partially active	832:857	We were able to establish storage conditions that allowed us to keep the toxin partially active for up to 60 days.
29902539	4	55	theme	cardiotoxic	650:660	arg1	glycoprotein					701:712	a large dimeric glycoprotein	685:712	a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability	685:760	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	4	55	theme	cardiotoxic	650:660	arg1	cytolysin					672:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	3	56	theme	optimal	528:534	arg1	conditions					544:553	optimal storage conditions	528:553	optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom	528:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	13	57	theme	fish	2170:2173	arg1	cytolysins					2175:2184	other fish cytolysins	2164:2184	other fish cytolysins	2164:2184	Taken together, our results could suggest that, as has been already reported for other fish cytolysins, Sp-CTx acts mostly through lipid-dependent pore formation not only in erythrocytes but also in other cell types, which could account for the pain observed upon envenomation.
29902539	9	58	dep	interaction	1497:1507	arg1	toxin					1517:1521	toxin	1517:1521	toxin	1517:1521	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	9	58	dep	interaction	1497:1507	arg1	lipid					1509:1513	lipid	1509:1513	lipid	1509:1513	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	12	59	theme	system	1986:1991	arg1	involvement					1950:1960	the involvement	1946:1960	the involvement of the kallikrein-kinin system in this response	1946:2008	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	9	60	theme	hemolytic	1366:1374	arg1	activity					1376:1383	The hemolytic activity	1362:1383	The hemolytic activity of Sp-CTx	1362:1393	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	8	61	dep	N-	1331:1332	arg1	complexes					1350:1358	complexes	1350:1358	complexes	1350:1358	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	4	62	theme	dimeric	693:699	arg1	glycoprotein					701:712	a large dimeric glycoprotein	685:712	a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability	685:760	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	4	62	theme	dimeric	693:699	arg1	cytolysin					672:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin	645:680	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	11	63	theme	first	1718:1722	arg1	time					1724:1727	first time	1718:1727	first time	1718:1727	Finally, we were able to show, for first time, that Sp-CTx is at least partially responsible for the pain and inflammation observed upon envenomation.
29902539	12	64	from	involvement	1950:1960	arg1	response					2001:2008	this response	1996:2008	this response	1996:2008	However, while the edema induced by Sp-CTx was reduced by pre-treatment with aprotinin and HOE-140, pointing to the involvement of the kallikrein-kinin system in this response, these drugs had no significant effect in the toxin-induced nociception.
29902539	8	65	theme	typical	1209:1215	arg1	N-					1217:1218	typical N-	1209:1218	typical N-	1209:1218	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	0	66	theme	toxin	69:73	arg1	characterization					16:31	the characterization	12:31	the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx)	12:82	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	3	67	theme	bioactive	577:585	arg1	component					587:595	the major bioactive component	567:595	the major bioactive component from the scorpionfish Scorpaena plumieri venom	567:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	3	67	theme	bioactive	577:585	arg1	Sp-CTx					559:564	Sp-CTx	559:564	Sp-CTx	559:564	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	9	68	from	interaction	1497:1507	arg1	mechanism					1545:1553	the pore-formation mechanism	1526:1553	the pore-formation mechanism of action of this toxin	1526:1577	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	6	69	theme	%	968:968	arg1	glycerol					957:964	glycerol	957:964	glycerol 10%	957:968	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	13	70	dep	suggest	2117:2123	arg1	could					2111:2115	could	2111:2115	could	2111:2115	Taken together, our results could suggest that, as has been already reported for other fish cytolysins, Sp-CTx acts mostly through lipid-dependent pore formation not only in erythrocytes but also in other cell types, which could account for the pain observed upon envenomation.
29902539	6	71	theme	glycerol	957:964	arg1	presence					945:952	the presence	941:952	the presence of glycerol 10% in a pH 7.4 solution	941:989	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	8	72	theme	linked	1227:1232	arg1	residues					1250:1257	O- linked glycoconjugated residues	1224:1257	O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes)	1224:1359	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	72	theme	linked	1227:1232	arg1	N-acetylglucosamine					1276:1294	galactose (1-4) N-acetylglucosamine	1260:1294	galactose (1-4) N-acetylglucosamine	1260:1294	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	72	theme	linked	1227:1232	arg1	acid					1307:1310	sialic acid	1300:1310	sialic acid (2-3)	1300:1316	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	4	73	theme	pore-forming	741:752	arg1	ability					754:760	pore-forming ability	741:760	pore-forming ability	741:760	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	8	74	theme	galactose	1260:1268	arg1	residues					1250:1257	O- linked glycoconjugated residues	1224:1257	O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes)	1224:1359	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	74	theme	galactose	1260:1268	arg1	N-acetylglucosamine					1276:1294	galactose (1-4) N-acetylglucosamine	1260:1294	galactose (1-4) N-acetylglucosamine	1260:1294	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	5	75	theme	storage	789:795	arg1	conditions					797:806	storage conditions	789:806	storage conditions that allowed us to keep the toxin partially active for up to 60 days	789:875	We were able to establish storage conditions that allowed us to keep the toxin partially active for up to 60 days.
29902539	9	76	theme	electrostatic	1483:1495	arg1	interaction					1497:1507	a direct electrostatic interaction lipid - toxin	1474:1521	a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin	1474:1577	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	14	77	theme	fish	2449:2452	arg1	cytolysins					2454:2463	fish cytolysins	2449:2463	fish cytolysins	2449:2463	We believe that the present work paves the way towards the complete characterization of fish cytolysins.
29902539	1	78	theme	neurotoxic	259:268	arg1	Proteins					85:92	Proteins	85:92	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms	85:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	1	78	theme	neurotoxic	259:268	arg1	effects					300:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	4	79	dep	glycoprotein	701:712	arg1	subunits					715:722	subunits	715:722	subunits of ≈65 kDa	715:733	This cardiotoxic hemolytic cytolysin is a large dimeric glycoprotein (subunits of ≈65 kDa) with pore-forming ability.
29902539	6	80	from	-80	922:924	arg1	Sp-CTx					912:917	Sp-CTx	912:917	Sp-CTx at -80 and -196 °C	912:936	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	3	81	theme	plumieri	629:636	arg1	venom					638:642	the scorpionfish Scorpaena plumieri venom	602:642	the scorpionfish Scorpaena plumieri venom	602:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	2	82	dep	toxins	331:336	arg1	referred					379:386	referred	379:386	referred to as cytolysins	379:403	These multifunctional toxins, described as protein lethal factors and referred to as cytolysins, are known to be extremely labile molecules.
29902539	2	82	dep	toxins	331:336	arg1	described					339:347	described	339:347	described as protein lethal factors	339:373	These multifunctional toxins, described as protein lethal factors and referred to as cytolysins, are known to be extremely labile molecules.
29902539	2	83	theme	lethal	360:365	arg1	factors					367:373	protein lethal factors	352:373	protein lethal factors	352:373	These multifunctional toxins, described as protein lethal factors and referred to as cytolysins, are known to be extremely labile molecules.
29902539	1	84	theme	cardiotoxic	271:281	arg1	Proteins					85:92	Proteins	85:92	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms	85:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	1	84	theme	cardiotoxic	271:281	arg1	effects					300:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	6	85	from	-196 °C	930:936	arg1	Sp-CTx					912:917	Sp-CTx	912:917	Sp-CTx at -80 and -196 °C	912:936	Stability was achieved by storing Sp-CTx at -80 and -196 °C in the presence of glycerol 10% in a pH 7.4 solution.
29902539	3	86	theme	scorpionfish	606:617	arg1	venom					638:642	the scorpionfish Scorpaena plumieri venom	602:642	the scorpionfish Scorpaena plumieri venom	602:642	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	8	87	theme	sialic	1300:1305	arg1	residues					1250:1257	O- linked glycoconjugated residues	1224:1257	O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes)	1224:1359	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	87	theme	sialic	1300:1305	arg1	2-3					1313:1315	2-3	1313:1315	2-3	1313:1315	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	8	87	theme	sialic	1300:1305	arg1	acid					1307:1310	sialic acid	1300:1310	sialic acid (2-3)	1300:1316	Furthermore, the toxin exhibited its maximal hemolytic activity at pH between 8 and 9, displaying typical N- and O- linked glycoconjugated residues (galactose (1-4) N-acetylglucosamine and sialic acid (2-3) galactose in N- and/or O-glycan complexes).
29902539	0	88	theme	plumieri	50:57	arg1	Sp-CTx					76:81	Sp-CTx	76:81	Sp-CTx	76:81	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	0	88	theme	plumieri	50:57	arg1	toxin					69:73	the Scorpaena plumieri cytolytic toxin	36:73	the Scorpaena plumieri cytolytic toxin (Sp-CTx)	36:82	Advances in the characterization of the Scorpaena plumieri cytolytic toxin (Sp-CTx).
29902539	1	89	theme	inflammatory	287:298	arg1	Proteins					85:92	Proteins	85:92	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms	85:167	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	1	89	theme	inflammatory	287:298	arg1	effects					300:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	neurotoxic, cardiotoxic and inflammatory effects	259:306	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	2	90	theme	labile	432:437	arg1	molecules					439:447	extremely labile molecules	422:447	extremely labile molecules	422:447	These multifunctional toxins, described as protein lethal factors and referred to as cytolysins, are known to be extremely labile molecules.
29902539	10	91	theme	hemolytic	1614:1622	arg1	activity					1624:1631	the hemolytic activity	1610:1631	the hemolytic activity	1610:1631	In addition, we observed that the hemolytic activity was inhibited by increasing doses of cholesterol.
29902539	13	92	theme	pore	2230:2233	arg1	formation					2235:2243	lipid-dependent pore formation	2214:2243	lipid-dependent pore formation	2214:2243	Taken together, our results could suggest that, as has been already reported for other fish cytolysins, Sp-CTx acts mostly through lipid-dependent pore formation not only in erythrocytes but also in other cell types, which could account for the pain observed upon envenomation.
29902539	3	93	theme	present	457:463	arg1	work					465:468	the present work	453:468	the present work	453:468	In the present work, we endeavored to overcome this constraint by determining optimal storage conditions for Sp-CTx, the major bioactive component from the scorpionfish Scorpaena plumieri venom.
29902539	1	94	theme	effects	209:215	arg1	majority					193:200	the majority	189:200	the majority of the effects observed upon envenomation	189:242	Proteins that account for the hemolytic activity found in scorpaeniform fish venoms are responsible for the majority of the effects observed upon envenomation, for instance, neurotoxic, cardiotoxic and inflammatory effects.
29902539	9	95	theme	action	1558:1563	arg1	mechanism					1545:1553	the pore-formation mechanism	1526:1553	the pore-formation mechanism of action of this toxin	1526:1577	The hemolytic activity of Sp-CTx was inhibited by phosphatidylglycerol and phosphatidylethanolamine, suggesting a direct electrostatic interaction lipid - toxin in the pore-formation mechanism of action of this toxin.
29902539	7	96	theme	zinc	1100:1103	arg1	ions					1105:1108	zinc ions	1100:1108	zinc ions	1100:1108	It was demonstrated that the hemolytic activity of Sp-CTx is calcium dependent, being abolished by EDTA and zinc ions.
28389149	2	0	theme	channel	504:510	arg1	isoforms					512:519	channel isoforms	504:519	channel isoforms	504:519	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	3	1	theme	parallel	759:766	arg1	chemistry					778:786	parallel medicinal chemistry	759:786	parallel medicinal chemistry	759:786	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	0	2	theme	inhibitors	77:86	arg1	Discovery					0:8	Discovery	0:8	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.	0:114	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	3	3	theme	cardiovascular	705:718	arg1	effects					725:731	cardiovascular side effects	705:731	cardiovascular side effects	705:731	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	4	theme	Nav	677:679	arg1	isoform					681:687	the Nav isoform	673:687	the Nav isoform responsible for cardiovascular side effects	673:731	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	4	theme	Nav	677:679	arg1	Nav1.5					665:670	Nav1.5	665:670	Nav1.5	665:670	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	4	5	theme	behavioral	919:928	arg1	efficacy					930:937	behavioral efficacy	919:937	behavioral efficacy in a rodent pain model	919:960	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	3	6	theme	selectivity	648:658	arg1	levels					638:643	high levels	633:643	high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization	633:828	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	0	7	theme	pain	93:96	arg1	efficacy					98:105	pain efficacy	93:105	pain efficacy in mice	93:113	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	1	8	from	mutations	317:325	arg1	man					251:253	man	251:253	man eliciting a variety of painful disorders	251:294	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	3	9	theme	novel	558:562	arg1	series					564:569	a novel series	556:569	a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors	556:626	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	4	10	theme	itch	987:990	arg1	model					992:996	a mouse itch model	979:996	a mouse itch model suggestive of target modulation	979:1028	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	4	11	from	potency	897:903	arg1	model					956:960	a rodent pain model	942:960	a rodent pain model	942:960	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	4	12	theme	excellent	887:895	arg1	potency					897:903	excellent potency	887:903	excellent potency	887:903	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	2	13	theme	Nav1	412:415	arg1	inhibition					417:426	Nav1 inhibition	412:426	Nav1 inhibition	412:426	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	4	14	theme	mouse	981:985	arg1	model					992:996	a mouse itch model	979:996	a mouse itch model suggestive of target modulation	979:1028	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	3	15	with	discovery	543:551	arg1	levels					638:643	high levels	633:643	high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization	633:828	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	1	16	theme	validated	173:181	arg1	target					183:188	a genetically validated target	159:188	a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain	159:357	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	16	theme	validated	173:181	arg1	channel					141:147	The voltage-gated sodium channel Nav1.7	116:154	The voltage-gated sodium channel Nav1.7	116:154	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	3	17	theme	judicious	742:750	arg1	use					752:754	judicious use	742:754	judicious use of parallel medicinal chemistry	742:786	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	4	18	theme	suggestive	998:1007	arg1	model					992:996	a mouse itch model	979:996	a mouse itch model suggestive of target modulation	979:1028	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	3	19	theme	chemistry	778:786	arg1	use					752:754	judicious use	742:754	judicious use of parallel medicinal chemistry	742:786	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	20	theme	bioavailable	581:592	arg1	inhibitors					617:626	orally bioavailable arylsulfonamide Nav1.7 inhibitors	574:626	orally bioavailable arylsulfonamide Nav1.7 inhibitors	574:626	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	2	21	theme	garner	392:397	arg1	efficacy					399:406	garner efficacy	392:406	garner efficacy	392:406	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	1	22	theme	painful	278:284	arg1	disorders					286:294	painful disorders	278:294	painful disorders	278:294	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	3	23	theme	series	564:569	arg1	discovery					543:551	the discovery	539:551	the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization	539:828	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	2	24	theme	side	445:448	arg1	profiles					457:464	undesirable side effect profiles	433:464	undesirable side effect profiles	433:464	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	2	25	theme	effect	450:455	arg1	profiles					457:464	undesirable side effect profiles	433:464	undesirable side effect profiles	433:464	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	1	26	theme	disorders	286:294	arg1	disorders					286:294	painful disorders	278:294	painful disorders	278:294	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	26	theme	disorders	286:294	arg1	variety					267:273	a variety	265:273	a variety of painful disorders	265:294	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	4	27	from	efficacy	967:974	arg1	model					956:960	a rodent pain model	942:960	a rodent pain model	942:960	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	2	28	theme	undesirable	433:443	arg1	profiles					457:464	undesirable side effect profiles	433:464	undesirable side effect profiles	433:464	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	2	29	theme	selectivity	487:497	arg1	lack					479:482	their lack	473:482	their lack of selectivity over channel isoforms	473:519	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	3	30	theme	medicinal	768:776	arg1	chemistry					778:786	parallel medicinal chemistry	759:786	parallel medicinal chemistry	759:786	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	31	theme	inhibitors	617:626	arg1	series					564:569	a novel series	556:569	a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors	556:626	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	4	32	theme	modulation	1019:1028	arg1	suggestive					998:1007	suggestive	998:1007	suggestive	998:1007	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	1	33	theme	loss-of-function	300:315	arg1	mutations					317:325	loss-of-function mutations	300:325	loss-of-function mutations	300:325	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	34	with	treatment	198:206	arg1	mutations					238:246	gain-of-function mutations	221:246	gain-of-function mutations in man eliciting a variety of painful disorders	221:294	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	34	with	treatment	198:206	arg1	mutations					317:325	loss-of-function mutations	300:325	loss-of-function mutations	300:325	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	35	theme	pain	211:214	arg1	treatment					198:206	the treatment	194:206	the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain	194:357	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	3	36	theme	optimization	817:828	arg1	levels					638:643	high levels	633:643	high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization	633:828	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	1	37	from	mutations	238:246	arg1	man					251:253	man	251:253	man eliciting a variety of painful disorders	251:294	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	3	38	theme	arylsulfonamide	594:608	arg1	inhibitors					617:626	orally bioavailable arylsulfonamide Nav1.7 inhibitors	574:626	orally bioavailable arylsulfonamide Nav1.7 inhibitors	574:626	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	39	theme	side	720:723	arg1	effects					725:731	cardiovascular side effects	705:731	cardiovascular side effects	705:731	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	40	theme	physicochemical	792:806	arg1	optimization					817:828	physicochemical property optimization	792:828	physicochemical property optimization	792:828	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	4	41	from	efficacy	930:937	arg1	model					956:960	a rodent pain model	942:960	a rodent pain model	942:960	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	3	42	theme	responsible	689:699	arg1	isoform					681:687	the Nav isoform	673:687	the Nav isoform responsible for cardiovascular side effects	673:731	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	42	theme	responsible	689:699	arg1	Nav1.5					665:670	Nav1.5	665:670	Nav1.5	665:670	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	43	theme	Nav1.7	610:615	arg1	inhibitors					617:626	orally bioavailable arylsulfonamide Nav1.7 inhibitors	574:626	orally bioavailable arylsulfonamide Nav1.7 inhibitors	574:626	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	3	44	theme	property	808:815	arg1	optimization					817:828	physicochemical property optimization	792:828	physicochemical property optimization	792:828	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	4	45	theme	pain	951:954	arg1	model					956:960	a rodent pain model	942:960	a rodent pain model	942:960	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	2	46	contain	have	428:431	arg1	drugs					375:379	drugs	375:379	drugs thought to garner efficacy via Nav1 inhibition	375:426	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	2	46	contain	have	428:431	arg2	profiles					457:464	undesirable side effect profiles	433:464	undesirable side effect profiles	433:464	Unfortunately, drugs thought to garner efficacy via Nav1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.
28389149	0	47	with	Discovery	0:8	arg1	efficacy					98:105	pain efficacy	93:105	pain efficacy in mice	93:113	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	1	48	theme	voltage-gated	120:132	arg1	target					183:188	a genetically validated target	159:188	a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain	159:357	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	48	theme	voltage-gated	120:132	arg1	channel					141:147	The voltage-gated sodium channel Nav1.7	116:154	The voltage-gated sodium channel Nav1.7	116:154	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	4	49	theme	rodent	944:949	arg1	model					956:960	a rodent pain model	942:960	a rodent pain model	942:960	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	0	50	from	efficacy	98:105	arg1	mice					110:113	mice	110:113	mice	110:113	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	0	51	dep	selective	13:21	arg1	bioavailable					31:42	bioavailable	31:42	bioavailable	31:42	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	0	51	dep	selective	13:21	arg1	N-linked					45:52	N-linked	45:52	N-linked	45:52	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	1	52	theme	sodium	134:139	arg1	target					183:188	a genetically validated target	159:188	a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain	159:357	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	52	theme	sodium	134:139	arg1	channel					141:147	The voltage-gated sodium channel Nav1.7	116:154	The voltage-gated sodium channel Nav1.7	116:154	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	1	53	theme	gain-of-function	221:236	arg1	mutations					238:246	gain-of-function mutations	221:246	gain-of-function mutations in man eliciting a variety of painful disorders	221:294	The voltage-gated sodium channel Nav1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain.
28389149	0	54	theme	Nav1.7	70:75	arg1	inhibitors					77:86	selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors	13:86	selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors	13:86	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	3	55	theme	high	633:636	arg1	levels					638:643	high levels	633:643	high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization	633:828	Herein we report the discovery of a novel series of orally bioavailable arylsulfonamide Nav1.7 inhibitors with high levels of selectivity over Nav1.5, the Nav isoform responsible for cardiovascular side effects, through judicious use of parallel medicinal chemistry and physicochemical property optimization.
28389149	0	56	theme	arylsulfonamide	54:68	arg1	inhibitors					77:86	selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors	13:86	selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors	13:86	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	4	57	theme	target	1012:1017	arg1	modulation					1019:1028	target modulation	1012:1028	target modulation	1012:1028	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
28389149	0	58	theme	selective	13:21	arg1	inhibitors					77:86	selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors	13:86	selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors	13:86	Discovery of selective, orally bioavailable, N-linked arylsulfonamide Nav1.7 inhibitors with pain efficacy in mice.
28389149	4	59	from	selectivity	906:916	arg1	model					956:960	a rodent pain model	942:960	a rodent pain model	942:960	This effort produced inhibitors such as compound 5 with excellent potency, selectivity, behavioral efficacy in a rodent pain model, and efficacy in a mouse itch model suggestive of target modulation.
31604106	6	0	theme	key	1105:1107	arg1	genes					1120:1124	key regulatory genes	1105:1124	key regulatory genes of O-glycan precursor synthesis	1105:1156	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	6	0	theme	key	1105:1107	arg1	transaminase					1022:1033	Glutamine-fructose-6-phosphate transaminase 2	991:1035	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2)	991:1043	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	12	1	gly	O-glycosylation	2268:2282	arg1	protein					2321:2327	recombinant hCG protein	2305:2327	recombinant hCG protein	2305:2327	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	16	2	from	factors	2788:2794	arg1	cells					2849:2853	CHO cells	2845:2853	CHO cells	2845:2853	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	3	3	from	expression	484:493	arg1	cells					553:557	Chinese hamster ovary (CHO) cells	525:557	Chinese hamster ovary (CHO) cells	525:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	11	4	theme	glycoprotein-N-acetylgalactosamine	1931:1964	arg1	3-beta-galactosyltransferase					1966:1993	glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase	1931:1993	glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1)	1931:2003	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	4	theme	glycoprotein-N-acetylgalactosamine	1931:1964	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	4	theme	glycoprotein-N-acetylgalactosamine	1931:1964	arg1	C1galt1					1996:2002	C1galt1	1996:2002	C1galt1	1996:2002	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	13	5	theme	synthesis	2390:2398	arg1	Galnt1					2330:2335	Galnt1	2330:2335	Galnt1	2330:2335	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	13	5	theme	synthesis	2390:2398	arg1	enzyme					2359:2364	the major limiting enzyme	2340:2364	the major limiting enzyme of O-glycan sugar chain synthesis	2340:2398	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	13	6	theme	major	2344:2348	arg1	Galnt1					2330:2335	Galnt1	2330:2335	Galnt1	2330:2335	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	13	6	theme	major	2344:2348	arg1	enzyme					2359:2364	the major limiting enzyme	2340:2364	the major limiting enzyme of O-glycan sugar chain synthesis	2340:2398	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	1	7	gly	glycoprotein	185:196	arg1	glycoprotein					185:196	a glycoprotein hormone	183:204	a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges	183:303	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	3	8	theme	hCG	510:512	arg1	protein					514:520	recombinant hCG protein	498:520	recombinant hCG protein	498:520	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	11	9	link	O-linked	2006:2013	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	9	link	O-linked	2006:2013	arg1	Ogt					2048:2050	Ogt	2048:2050	Ogt	2048:2050	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	9	link	O-linked	2006:2013	arg1	transferase					2035:2045	O-linked N-acetylglucosamine transferase	2006:2045	O-linked N-acetylglucosamine transferase (Ogt)	2006:2051	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	12	10	theme	proteins	2258:2265	arg1	galactosylation					2225:2239	the total galactosylation	2215:2239	the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein	2215:2327	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	10	11	theme	limiting	1652:1659	arg1	enzyme					1661:1666	the major limiting enzyme	1642:1666	the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production	1642:1740	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	10	11	theme	limiting	1652:1659	arg1	Ugp2					1634:1637	Ugp2	1634:1637	Ugp2	1634:1637	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	11	12	theme	polypeptide	1857:1867	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	12	theme	polypeptide	1857:1867	arg1	synthase					1921:1928	Core 1 synthase	1914:1928	Core 1 synthase	1914:1928	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	12	theme	polypeptide	1857:1867	arg1	Galnt1					1905:1910	Galnt1	1905:1910	Galnt1	1905:1910	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	12	theme	polypeptide	1857:1867	arg1	Hexosaminidase					2057:2070	Hexosaminidase	2057:2070	Hexosaminidase (Hex)	2057:2076	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	12	theme	polypeptide	1857:1867	arg1	3-beta-galactosyltransferase					1966:1993	glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase	1931:1993	glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1)	1931:2003	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	12	theme	polypeptide	1857:1867	arg1	transferase					2035:2045	O-linked N-acetylglucosamine transferase	2006:2045	O-linked N-acetylglucosamine transferase (Ogt)	2006:2051	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	15	13	theme	protein	2720:2726	arg1	level					2728:2732	the recombinant hCG protein level	2700:2732	the recombinant hCG protein level	2700:2732	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	8	14	gly	O-glycosylation	1517:1531	arg1	proteins					1500:1507	intracellular proteins	1486:1507	intracellular proteins	1486:1507	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	8	14	gly	O-glycosylation	1517:1531	arg1	protein					1552:1558	recombinant hCG protein	1536:1558	recombinant hCG protein	1536:1558	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	4	15	theme	recombinant	594:604	arg1	expression					618:627	recombinant hCG protein expression	594:627	recombinant hCG protein expression	594:627	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	12	16	theme	protein	2321:2327	arg1	O-glycosylation					2268:2282	O-glycosylation	2268:2282	O-glycosylation	2268:2282	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	12	16	theme	protein	2321:2327	arg1	stability					2292:2300	the stability	2288:2300	the stability of recombinant hCG protein	2288:2327	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	12	16	theme	protein	2321:2327	arg1	proteins					2258:2265	intracellular proteins	2244:2265	intracellular proteins	2244:2265	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	0	17	theme	hamster	124:130	arg1	cells					138:142	Chinese hamster ovary cells	116:142	Chinese hamster ovary cells	116:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	3	18	theme	hamster	533:539	arg1	cells					553:557	Chinese hamster ovary (CHO) cells	525:557	Chinese hamster ovary (CHO) cells	525:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	15	19	theme	recombinant	2704:2714	arg1	level					2728:2732	the recombinant hCG protein level	2700:2732	the recombinant hCG protein level	2700:2732	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	8	20	theme	proteins	1500:1507	arg1	levels					1476:1481	the total galactosylation levels	1450:1481	the total galactosylation levels of intracellular proteins	1450:1507	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	8	20	theme	proteins	1500:1507	arg1	O-glycosylation					1517:1531	the O-glycosylation	1513:1531	the O-glycosylation of recombinant hCG protein	1513:1558	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	4	21	theme	protein	610:616	arg1	expression					618:627	recombinant hCG protein expression	594:627	recombinant hCG protein expression	594:627	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	10	22	theme	O-glycan	1675:1682	arg1	synthesis					1694:1702	the O-glycan precursor synthesis	1671:1702	the O-glycan precursor synthesis	1671:1702	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	7	23	theme	Ugp2	1179:1182	arg1	overexpression					1184:1197	Ugp2 overexpression	1179:1197	Ugp2 overexpression	1179:1197	Ugp2 overexpression significantly increased the recombinant hCG protein level by 1.92 times compared to that of the control.
31604106	15	24	theme	major	2596:2600	arg1	gene					2611:2614	the major limiting gene	2592:2614	the major limiting gene of O-Glycan chain synthesis	2592:2642	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	15	24	theme	major	2596:2600	arg1	Galnt1					2584:2589	Galnt1	2584:2589	Galnt1	2584:2589	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	14	25	contain	had	2517:2519	arg2	effects					2533:2539	synergistic effects	2521:2539	synergistic effects	2521:2539	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
31604106	14	25	contain	had	2517:2519	arg1	both					2512:2515	both	2512:2515	both	2512:2515	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
31604106	0	26	from	production	58:67	arg1	cells					138:142	Chinese hamster ovary cells	116:142	Chinese hamster ovary cells	116:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	16	27	theme	effective	2871:2879	arg1	strategy					2903:2910	an effective expression regulation strategy	2868:2910	an effective expression regulation strategy	2868:2910	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	8	28	theme	analysis	1317:1324	arg1	analysis					1385:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	5	29	theme	protein	913:919	arg1	expression					883:892	the expression	879:892	the expression of recombinant hCG protein	879:919	The results indicated that O-glycosylation was indeed limiting in the expression of recombinant hCG protein, and N-acetylgalactosamine (GalNAc) was the major limiting precursor.
31604106	1	30	dep	subunit	253:259	arg1	an					248:249	an	248:249	an	248:249	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	16	31	theme	regulation	2892:2901	arg1	strategy					2903:2910	an effective expression regulation strategy	2868:2910	an effective expression regulation strategy	2868:2910	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	8	32	theme	Phaseolus	1330:1338	arg1	leucoagglutinin					1349:1363	Phaseolus vulgaris leucoagglutinin	1330:1363	Phaseolus vulgaris leucoagglutinin (PHA-L)	1330:1371	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	8	32	theme	Phaseolus	1330:1338	arg1	PHA-L					1366:1370	PHA-L	1366:1370	PHA-L	1366:1370	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	14	33	theme	recombinant	2463:2473	arg1	level					2487:2491	the recombinant hCG protein level	2459:2491	the recombinant hCG protein level	2459:2491	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
31604106	11	34	theme	O-glycan	1803:1810	arg1	synthesis					1824:1832	O-glycan sugar chain synthesis	1803:1832	O-glycan sugar chain synthesis	1803:1832	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	4	35	theme	down	705:708	arg1	genes					725:729	knocking down key regulatory genes	696:729	knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis	696:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	8	36	theme	hCG	1548:1550	arg1	protein					1552:1558	recombinant hCG protein	1536:1558	recombinant hCG protein	1536:1558	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	4	37	theme	O-glycan	653:660	arg1	precursors					662:671	O-glycan precursors	653:671	O-glycan precursors	653:671	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	15	38	dep	precursors	2649:2658	arg1	Gal					2671:2673	Gal	2671:2673	Gal	2671:2673	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	15	38	dep	precursors	2649:2658	arg1	GalNAc					2660:2665	GalNAc	2660:2665	GalNAc	2660:2665	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	15	38	dep	precursors	2649:2658	arg1	precursors					2649:2658	the precursors GalNAc and Gal	2645:2673	the precursors GalNAc and Gal	2645:2673	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	11	39	theme	genes	1794:1798	arg1	effects					1760:1766	the effects	1756:1766	the effects	1756:1766	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	39	theme	genes	1794:1798	arg1	mechanisms					1772:1781	mechanisms	1772:1781	mechanisms	1772:1781	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	1	40	theme	chorionic	151:159	arg1	hormone					198:204	a glycoprotein hormone	183:204	a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges	183:303	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	1	40	theme	chorionic	151:159	arg1	hCG					175:177	hCG	175:177	hCG	175:177	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	1	40	theme	chorionic	151:159	arg1	gonadotropin					161:172	Human chorionic gonadotropin	145:172	Human chorionic gonadotropin (hCG)	145:178	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	16	41	gly	O-glycosylation	2799:2813	arg1	protein					2834:2840	recombinant hCG protein	2818:2840	recombinant hCG protein	2818:2840	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	12	42	theme	protein	2174:2180	arg1	level					2182:2186	the recombinant hCG protein level	2154:2186	the recombinant hCG protein level	2154:2186	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	14	43	theme	Galnt1	2428:2433	arg1	Overexpression					2401:2414	Overexpression	2401:2414	Overexpression of Ugp2 and Galnt1	2401:2433	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
31604106	0	44	theme	recombinant	72:82	arg1	gonadotropin					100:111	recombinant human chorionic gonadotropin	72:111	recombinant human chorionic gonadotropin	72:111	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	5	45	theme	recombinant	897:907	arg1	protein					913:919	recombinant hCG protein	897:919	recombinant hCG protein	897:919	The results indicated that O-glycosylation was indeed limiting in the expression of recombinant hCG protein, and N-acetylgalactosamine (GalNAc) was the major limiting precursor.
31604106	6	46	theme	Glutamine-fructose-6-phosphate	991:1020	arg1	transaminase					1022:1033	Glutamine-fructose-6-phosphate transaminase 2	991:1035	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2)	991:1043	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	6	46	theme	Glutamine-fructose-6-phosphate	991:1020	arg1	Gfat2					1038:1042	Gfat2	1038:1042	Gfat2	1038:1042	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	6	46	theme	Glutamine-fructose-6-phosphate	991:1020	arg1	genes					1120:1124	key regulatory genes	1105:1124	key regulatory genes of O-glycan precursor synthesis	1105:1156	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	16	47	theme	expression	2881:2890	arg1	strategy					2903:2910	an effective expression regulation strategy	2868:2910	an effective expression regulation strategy	2868:2910	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	8	48	theme	lectin	1373:1378	arg1	analysis					1385:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	14	49	theme	Ugp2	2419:2422	arg1	Overexpression					2401:2414	Overexpression	2401:2414	Overexpression of Ugp2 and Galnt1	2401:2433	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
31604106	11	50	theme	chain	1818:1822	arg1	synthesis					1824:1832	O-glycan sugar chain synthesis	1803:1832	O-glycan sugar chain synthesis	1803:1832	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	0	51	theme	chorionic	90:98	arg1	gonadotropin					100:111	recombinant human chorionic gonadotropin	72:111	recombinant human chorionic gonadotropin	72:111	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	15	52	theme	synthesis	2634:2642	arg1	gene					2611:2614	the major limiting gene	2592:2614	the major limiting gene of O-Glycan chain synthesis	2592:2642	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	15	52	theme	synthesis	2634:2642	arg1	Galnt1					2584:2589	Galnt1	2584:2589	Galnt1	2584:2589	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	16	53	theme	protein	2834:2840	arg1	O-glycosylation					2799:2813	O-glycosylation	2799:2813	O-glycosylation of recombinant hCG protein	2799:2840	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	10	54	theme	hCG	1719:1721	arg1	production					1731:1740	recombinant hCG protein production	1707:1740	recombinant hCG protein production	1707:1740	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	7	55	theme	recombinant	1227:1237	arg1	level					1251:1255	the recombinant hCG protein level	1223:1255	the recombinant hCG protein level	1223:1255	Ugp2 overexpression significantly increased the recombinant hCG protein level by 1.92 times compared to that of the control.
31604106	15	56	theme	O-Glycan	2619:2626	arg1	synthesis					2634:2642	O-Glycan chain synthesis	2619:2642	O-Glycan chain synthesis	2619:2642	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	5	57	theme	limiting	971:978	arg1	precursor					980:988	the major limiting precursor	961:988	the major limiting precursor	961:988	The results indicated that O-glycosylation was indeed limiting in the expression of recombinant hCG protein, and N-acetylgalactosamine (GalNAc) was the major limiting precursor.
31604106	5	57	theme	limiting	971:978	arg1	N-acetylgalactosamine					926:946	N-acetylgalactosamine	926:946	N-acetylgalactosamine (GalNAc)	926:955	The results indicated that O-glycosylation was indeed limiting in the expression of recombinant hCG protein, and N-acetylgalactosamine (GalNAc) was the major limiting precursor.
31604106	16	58	theme	O-glycosylation	2799:2813	arg1	factors					2788:2794	the major limiting factors	2769:2794	the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells	2769:2853	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	11	59	theme	Core	1914:1917	arg1	synthase					1921:1928	Core 1 synthase	1914:1928	Core 1 synthase	1914:1928	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	59	theme	Core	1914:1917	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	4	60	theme	regulatory	714:723	arg1	genes					725:729	knocking down key regulatory genes	696:729	knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis	696:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	3	61	theme	mRNA	409:412	arg1	step					471:474	a severely limiting step	451:474	a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells	451:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	3	61	theme	mRNA	409:412	arg1	translation					394:404	the translation	390:404	the translation of mRNA to polypeptides of the β subunit	390:445	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	16	62	theme	recombinant	2818:2828	arg1	protein					2834:2840	recombinant hCG protein	2818:2840	recombinant hCG protein	2818:2840	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	3	63	theme	Previous	357:364	arg1	studies					366:372	Previous studies	357:372	Previous studies	357:372	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	3	64	theme	subunit	439:445	arg1	polypeptides					417:428	polypeptides	417:428	polypeptides of the β subunit	417:445	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	13	65	theme	limiting	2350:2357	arg1	Galnt1					2330:2335	Galnt1	2330:2335	Galnt1	2330:2335	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	13	65	theme	limiting	2350:2357	arg1	enzyme					2359:2364	the major limiting enzyme	2340:2364	the major limiting enzyme of O-glycan sugar chain synthesis	2340:2398	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	6	66	theme	diphosphate-glucose	1057:1075	arg1	pyrophosphorylase					1077:1093	Uridine diphosphate-glucose pyrophosphorylase 2	1049:1095	Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2)	1049:1102	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	6	66	theme	diphosphate-glucose	1057:1075	arg1	Ugp2					1098:1101	Ugp2	1098:1101	Ugp2	1098:1101	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	0	67	theme	O-glycosylation	20:34	arg1	strategy					36:43	enhanced O-glycosylation strategy	11:43	enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells	11:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	16	68	theme	CHO	2845:2847	arg1	cells					2849:2853	CHO cells	2845:2853	CHO cells	2845:2853	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	8	69	theme	total	1454:1458	arg1	levels					1476:1481	the total galactosylation levels	1450:1481	the total galactosylation levels of intracellular proteins	1450:1507	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	3	70	theme	limiting	462:469	arg1	step					471:474	a severely limiting step	451:474	a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells	451:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	3	70	theme	limiting	462:469	arg1	translation					394:404	the translation	390:404	the translation of mRNA to polypeptides of the β subunit	390:445	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	6	71	theme	precursor	1138:1146	arg1	synthesis					1148:1156	O-glycan precursor synthesis	1129:1156	O-glycan precursor synthesis	1129:1156	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	11	72	theme	key	1790:1792	arg1	genes					1794:1798	the key genes	1786:1798	the key genes of O-glycan sugar chain synthesis	1786:1832	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	72	theme	key	1790:1792	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	4	73	theme	sugar	776:780	arg1	chain					782:786	O-glycan sugar chain	767:786	O-glycan sugar chain synthesis	767:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	2	74	theme	β	310:310	arg1	subunit					312:318	The β subunit	306:318	The β subunit	306:318	The β subunit contains four O-glycosylation sites.
31604106	8	75	theme	leucoagglutinin	1349:1363	arg1	analysis					1385:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	9	76	theme	hCG	1582:1584	arg1	protein					1586:1592	the hCG protein	1578:1592	the hCG protein	1578:1592	The stability of the hCG protein to trypsin digestion was also enhanced.
31604106	10	77	theme	protein	1723:1729	arg1	production					1731:1740	recombinant hCG protein production	1707:1740	recombinant hCG protein production	1707:1740	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	4	78	theme	synthesis	788:796	arg1	genes					725:729	knocking down key regulatory genes	696:729	knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis	696:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	4	78	theme	synthesis	788:796	arg1	hydrolases					801:810	hydrolases	801:810	hydrolases	801:810	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	6	79	theme	regulatory	1109:1118	arg1	genes					1120:1124	key regulatory genes	1105:1124	key regulatory genes of O-glycan precursor synthesis	1105:1156	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	6	79	theme	regulatory	1109:1118	arg1	transaminase					1022:1033	Glutamine-fructose-6-phosphate transaminase 2	991:1035	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2)	991:1043	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	13	80	theme	O-glycan	2369:2376	arg1	synthesis					2390:2398	O-glycan sugar chain synthesis	2369:2398	O-glycan sugar chain synthesis	2369:2398	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	4	81	from	effects	564:570	arg1	expression					618:627	recombinant hCG protein expression	594:627	recombinant hCG protein expression	594:627	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	2	82	theme	O-glycosylation	334:348	arg1	sites					350:354	four O-glycosylation sites	329:354	four O-glycosylation sites	329:354	The β subunit contains four O-glycosylation sites.
31604106	10	83	from	enzyme	1661:1666	arg1	production					1731:1740	recombinant hCG protein production	1707:1740	recombinant hCG protein production	1707:1740	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	12	84	theme	hCG	2317:2319	arg1	protein					2321:2327	recombinant hCG protein	2305:2327	recombinant hCG protein	2305:2327	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	3	85	theme	protein	514:520	arg1	expression					484:493	the expression	480:493	the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells	480:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	1	86	theme	α	251:251	arg1	subunit					253:259	α subunit	251:259	α subunit	251:259	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	13	87	theme	sugar	2378:2382	arg1	synthesis					2390:2398	O-glycan sugar chain synthesis	2369:2398	O-glycan sugar chain synthesis	2369:2398	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	3	88	theme	recombinant	498:508	arg1	protein					514:520	recombinant hCG protein	498:520	recombinant hCG protein	498:520	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	8	89	theme	galactosylation	1460:1474	arg1	levels					1476:1481	the total galactosylation levels	1450:1481	the total galactosylation levels of intracellular proteins	1450:1507	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	12	90	theme	recombinant	2158:2168	arg1	level					2182:2186	the recombinant hCG protein level	2154:2186	the recombinant hCG protein level	2154:2186	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	3	91	theme	ovary	541:545	arg1	cells					553:557	Chinese hamster ovary (CHO) cells	525:557	Chinese hamster ovary (CHO) cells	525:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	12	92	theme	intracellular	2244:2256	arg1	O-glycosylation					2268:2282	O-glycosylation	2268:2282	O-glycosylation	2268:2282	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	12	92	theme	intracellular	2244:2256	arg1	stability					2292:2300	the stability	2288:2300	the stability of recombinant hCG protein	2288:2327	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	12	92	theme	intracellular	2244:2256	arg1	proteins					2258:2265	intracellular proteins	2244:2265	intracellular proteins	2244:2265	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	10	93	theme	major	1646:1650	arg1	enzyme					1661:1666	the major limiting enzyme	1642:1666	the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production	1642:1740	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	10	93	theme	major	1646:1650	arg1	Ugp2					1634:1637	Ugp2	1634:1637	Ugp2	1634:1637	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	0	94	theme	ovary	132:136	arg1	cells					138:142	Chinese hamster ovary cells	116:142	Chinese hamster ovary cells	116:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	14	95	theme	protein	2479:2485	arg1	level					2487:2491	the recombinant hCG protein level	2459:2491	the recombinant hCG protein level	2459:2491	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
31604106	3	96	theme	Chinese	525:531	arg1	cells					553:557	Chinese hamster ovary (CHO) cells	525:557	Chinese hamster ovary (CHO) cells	525:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	1	97	theme	glycoprotein	185:196	arg1	hormone					198:204	a glycoprotein hormone	183:204	a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges	183:303	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	1	97	theme	glycoprotein	185:196	arg1	gonadotropin					161:172	Human chorionic gonadotropin	145:172	Human chorionic gonadotropin (hCG)	145:178	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	13	98	theme	chain	2384:2388	arg1	synthesis					2390:2398	O-glycan sugar chain synthesis	2369:2398	O-glycan sugar chain synthesis	2369:2398	Galnt1 is the major limiting enzyme of O-glycan sugar chain synthesis.
31604106	10	99	theme	precursor	1684:1692	arg1	synthesis					1694:1702	the O-glycan precursor synthesis	1671:1702	the O-glycan precursor synthesis	1671:1702	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	15	100	theme	hCG	2716:2718	arg1	level					2728:2732	the recombinant hCG protein level	2700:2732	the recombinant hCG protein level	2700:2732	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	4	101	theme	hCG	606:608	arg1	expression					618:627	recombinant hCG protein expression	594:627	recombinant hCG protein expression	594:627	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	7	102	theme	hCG	1239:1241	arg1	level					1251:1255	the recombinant hCG protein level	1223:1255	the recombinant hCG protein level	1223:1255	Ugp2 overexpression significantly increased the recombinant hCG protein level by 1.92 times compared to that of the control.
31604106	3	103	theme	CHO	548:550	arg1	cells					553:557	Chinese hamster ovary (CHO) cells	525:557	Chinese hamster ovary (CHO) cells	525:557	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	15	104	theme	limiting	2602:2609	arg1	gene					2611:2614	the major limiting gene	2592:2614	the major limiting gene of O-Glycan chain synthesis	2592:2642	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	15	104	theme	limiting	2602:2609	arg1	Galnt1					2584:2589	Galnt1	2584:2589	Galnt1	2584:2589	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	5	105	theme	hCG	909:911	arg1	protein					913:919	recombinant hCG protein	897:919	recombinant hCG protein	897:919	The results indicated that O-glycosylation was indeed limiting in the expression of recombinant hCG protein, and N-acetylgalactosamine (GalNAc) was the major limiting precursor.
31604106	8	106	theme	recombinant	1536:1546	arg1	protein					1552:1558	recombinant hCG protein	1536:1558	recombinant hCG protein	1536:1558	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	8	107	theme	LC-MS/MS	1308:1315	arg1	analysis					1317:1324	LC-MS/MS analysis	1308:1324	LC-MS/MS analysis	1308:1324	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	14	108	theme	hCG	2475:2477	arg1	level					2487:2491	the recombinant hCG protein level	2459:2491	the recombinant hCG protein level	2459:2491	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
31604106	8	109	theme	protein	1552:1558	arg1	levels					1476:1481	the total galactosylation levels	1450:1481	the total galactosylation levels of intracellular proteins	1450:1507	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	8	109	theme	protein	1552:1558	arg1	O-glycosylation					1517:1531	the O-glycosylation	1513:1531	the O-glycosylation of recombinant hCG protein	1513:1558	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	4	110	theme	precursor	743:751	arg1	synthesis					753:761	O-glycan precursor synthesis	734:761	O-glycan precursor synthesis	734:761	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	4	111	theme	knocking	696:703	arg1	genes					725:729	knocking down key regulatory genes	696:729	knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis	696:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	11	112	theme	sugar	1812:1816	arg1	synthesis					1824:1832	O-glycan sugar chain synthesis	1803:1832	O-glycan sugar chain synthesis	1803:1832	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	15	113	theme	Galnt1	2584:2589	arg1	overexpression					2566:2579	overexpression	2566:2579	overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis	2566:2642	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	1	114	theme	Human	145:149	arg1	hormone					198:204	a glycoprotein hormone	183:204	a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges	183:303	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	1	114	theme	Human	145:149	arg1	hCG					175:177	hCG	175:177	hCG	175:177	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	1	114	theme	Human	145:149	arg1	gonadotropin					161:172	Human chorionic gonadotropin	145:172	Human chorionic gonadotropin (hCG)	145:178	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	8	115	theme	vulgaris	1340:1347	arg1	leucoagglutinin					1349:1363	Phaseolus vulgaris leucoagglutinin	1330:1363	Phaseolus vulgaris leucoagglutinin (PHA-L)	1330:1371	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	8	115	theme	vulgaris	1340:1347	arg1	PHA-L					1366:1370	PHA-L	1366:1370	PHA-L	1366:1370	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	7	116	theme	protein	1243:1249	arg1	level					1251:1255	the recombinant hCG protein level	1223:1255	the recombinant hCG protein level	1223:1255	Ugp2 overexpression significantly increased the recombinant hCG protein level by 1.92 times compared to that of the control.
31604106	0	117	theme	human	84:88	arg1	gonadotropin					100:111	recombinant human chorionic gonadotropin	72:111	recombinant human chorionic gonadotropin	72:111	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	15	118	theme	overexpression	2566:2579	arg1	results					2555:2561	the results	2551:2561	the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis	2551:2642	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	9	119	theme	protein	1586:1592	arg1	stability					1565:1573	The stability	1561:1573	The stability of the hCG protein to trypsin digestion	1561:1613	The stability of the hCG protein to trypsin digestion was also enhanced.
31604106	0	120	from	study	2:6	arg1	strategy					36:43	enhanced O-glycosylation strategy	11:43	enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells	11:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	12	121	theme	hCG	2170:2172	arg1	level					2182:2186	the recombinant hCG protein level	2154:2186	the recombinant hCG protein level	2154:2186	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	11	122	theme	hydrolases	1838:1847	arg1	effects					1760:1766	the effects	1756:1766	the effects	1756:1766	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	122	theme	hydrolases	1838:1847	arg1	mechanisms					1772:1781	mechanisms	1772:1781	mechanisms	1772:1781	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	0	123	theme	gonadotropin	100:111	arg1	production					58:67	improved production	49:67	improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells	49:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	2	124	contain	contains	320:327	arg1	subunit					312:318	The β subunit	306:318	The β subunit	306:318	The β subunit contains four O-glycosylation sites.
31604106	2	124	contain	contains	320:327	arg2	sites					350:354	four O-glycosylation sites	329:354	four O-glycosylation sites	329:354	The β subunit contains four O-glycosylation sites.
31604106	9	125	theme	trypsin	1597:1603	arg1	digestion					1605:1613	trypsin digestion	1597:1613	trypsin digestion	1597:1613	The stability of the hCG protein to trypsin digestion was also enhanced.
31604106	4	126	theme	O-glycan	734:741	arg1	synthesis					753:761	O-glycan precursor synthesis	734:761	O-glycan precursor synthesis	734:761	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	11	127	theme	synthesis	1824:1832	arg1	genes					1794:1798	the key genes	1786:1798	the key genes of O-glycan sugar chain synthesis	1786:1832	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	127	theme	synthesis	1824:1832	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	127	theme	synthesis	1824:1832	arg1	hydrolases					1838:1847	hydrolases	1838:1847	hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex),	1838:2077	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	0	128	theme	Chinese	116:122	arg1	cells					138:142	Chinese hamster ovary cells	116:142	Chinese hamster ovary cells	116:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	4	129	gly	O-glycosylation	575:589	arg1	hCG					606:608	recombinant hCG protein expression	594:627	recombinant hCG protein expression	594:627	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	4	129	gly	O-glycosylation	575:589	arg1	protein					610:616	recombinant hCG protein expression	594:627	recombinant hCG protein expression	594:627	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	5	130	theme	major	965:969	arg1	precursor					980:988	the major limiting precursor	961:988	the major limiting precursor	961:988	The results indicated that O-glycosylation was indeed limiting in the expression of recombinant hCG protein, and N-acetylgalactosamine (GalNAc) was the major limiting precursor.
31604106	5	130	theme	major	965:969	arg1	N-acetylgalactosamine					926:946	N-acetylgalactosamine	926:946	N-acetylgalactosamine (GalNAc)	926:955	The results indicated that O-glycosylation was indeed limiting in the expression of recombinant hCG protein, and N-acetylgalactosamine (GalNAc) was the major limiting precursor.
31604106	8	131	theme	blot	1380:1383	arg1	analysis					1385:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis	1304:1392	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	10	132	theme	recombinant	1707:1717	arg1	production					1731:1740	recombinant hCG protein production	1707:1740	recombinant hCG protein production	1707:1740	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	15	133	theme	chain	2628:2632	arg1	synthesis					2634:2642	O-Glycan chain synthesis	2619:2642	O-Glycan chain synthesis	2619:2642	Based on the results of overexpression of Galnt1, the major limiting gene of O-Glycan chain synthesis, the precursors GalNAc and Gal were added and increased the recombinant hCG protein level by 3.68 times.
31604106	16	134	theme	hCG	2830:2832	arg1	protein					2834:2840	recombinant hCG protein	2818:2840	recombinant hCG protein	2818:2840	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	4	135	theme	key	710:712	arg1	genes					725:729	knocking down key regulatory genes	696:729	knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis	696:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	10	136	theme	synthesis	1694:1702	arg1	enzyme					1661:1666	the major limiting enzyme	1642:1666	the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production	1642:1740	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	10	136	theme	synthesis	1694:1702	arg1	Ugp2					1634:1637	Ugp2	1634:1637	Ugp2	1634:1637	Ugp2 is the major limiting enzyme of the O-glycan precursor synthesis in recombinant hCG protein production.
31604106	0	137	theme	enhanced	11:18	arg1	strategy					36:43	enhanced O-glycosylation strategy	11:43	enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells	11:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	1	138	theme	β	265:265	arg1	subunit					267:273	β subunit	265:273	β subunit	265:273	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	8	139	theme	Ugp2	1406:1409	arg1	overexpression					1411:1424	Ugp2 overexpression	1406:1424	Ugp2 overexpression	1406:1424	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	8	140	theme	intracellular	1486:1498	arg1	proteins					1500:1507	intracellular proteins	1486:1507	intracellular proteins	1486:1507	The LC-MS/MS analysis and Phaseolus vulgaris leucoagglutinin (PHA-L) lectin blot analysis showed that Ugp2 overexpression significantly increased the total galactosylation levels of intracellular proteins and the O-glycosylation of recombinant hCG protein.
31604106	12	141	theme	total	2219:2223	arg1	galactosylation					2225:2239	the total galactosylation	2215:2239	the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein	2215:2327	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	6	142	theme	Uridine	1049:1055	arg1	pyrophosphorylase					1077:1093	Uridine diphosphate-glucose pyrophosphorylase 2	1049:1095	Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2)	1049:1102	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	6	142	theme	Uridine	1049:1055	arg1	Ugp2					1098:1101	Ugp2	1098:1101	Ugp2	1098:1101	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	11	143	theme	O-linked	2006:2013	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	143	theme	O-linked	2006:2013	arg1	Ogt					2048:2050	Ogt	2048:2050	Ogt	2048:2050	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	143	theme	O-linked	2006:2013	arg1	transferase					2035:2045	O-linked N-acetylglucosamine transferase	2006:2045	O-linked N-acetylglucosamine transferase (Ogt)	2006:2051	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	2	144	gly	O-glycosylation	334:348	arg2	sites					350:354	four O-glycosylation sites	329:354	four O-glycosylation sites	329:354	The β subunit contains four O-glycosylation sites.
31604106	2	144	gly	O-glycosylation	334:348	arg2	four					329:332	four	329:332	four	329:332	The β subunit contains four O-glycosylation sites.
31604106	3	145	theme	β	437:437	arg1	subunit					439:445	the β subunit	433:445	the β subunit	433:445	Previous studies have found that the translation of mRNA to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hCG protein in Chinese hamster ovary (CHO) cells.
31604106	0	146	theme	improved	49:56	arg1	production					58:67	improved production	49:67	improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells	49:142	A study on enhanced O-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in Chinese hamster ovary cells.
31604106	1	147	theme	disulfide	287:295	arg1	bridges					297:303	disulfide bridges	287:303	disulfide bridges	287:303	Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges.
31604106	6	148	theme	synthesis	1148:1156	arg1	genes					1120:1124	key regulatory genes	1105:1124	key regulatory genes of O-glycan precursor synthesis	1105:1156	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	6	148	theme	synthesis	1148:1156	arg1	transaminase					1022:1033	Glutamine-fructose-6-phosphate transaminase 2	991:1035	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2)	991:1043	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	12	149	theme	recombinant	2305:2315	arg1	protein					2321:2327	recombinant hCG protein	2305:2327	recombinant hCG protein	2305:2327	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	6	150	theme	O-glycan	1129:1136	arg1	synthesis					1148:1156	O-glycan precursor synthesis	1129:1156	O-glycan precursor synthesis	1129:1156	Glutamine-fructose-6-phosphate transaminase 2 (Gfat2) and Uridine diphosphate-glucose pyrophosphorylase 2 (Ugp2), key regulatory genes of O-glycan precursor synthesis, were overexpressed.
31604106	4	151	theme	synthesis	753:761	arg1	genes					725:729	knocking down key regulatory genes	696:729	knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis	696:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	4	151	theme	synthesis	753:761	arg1	hydrolases					801:810	hydrolases	801:810	hydrolases	801:810	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	4	152	theme	O-glycan	767:774	arg1	chain					782:786	O-glycan sugar chain	767:786	O-glycan sugar chain synthesis	767:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	16	153	theme	major	2773:2777	arg1	factors					2788:2794	the major limiting factors	2769:2794	the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells	2769:2853	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	12	154	theme	Galnt1	2122:2127	arg1	overexpression					2129:2142	Galnt1 overexpression	2122:2142	Galnt1 overexpression	2122:2142	The results indicated that Galnt1 overexpression increased the recombinant hCG protein level by 1.57 times and improved the total galactosylation of intracellular proteins, O-glycosylation and the stability of recombinant hCG protein.
31604106	16	155	theme	limiting	2779:2786	arg1	factors					2788:2794	the major limiting factors	2769:2794	the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells	2769:2853	This study revealed the major limiting factors of O-glycosylation of recombinant hCG protein in CHO cells and proposed an effective expression regulation strategy.
31604106	11	156	theme	N-acetylglucosamine	2015:2033	arg1	N-acetylgalactosaminyltransferase1					1869:1902	polypeptide N-acetylgalactosaminyltransferase1	1857:1902	polypeptide N-acetylgalactosaminyltransferase1 (Galnt1)	1857:1911	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	156	theme	N-acetylglucosamine	2015:2033	arg1	Ogt					2048:2050	Ogt	2048:2050	Ogt	2048:2050	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	11	156	theme	N-acetylglucosamine	2015:2033	arg1	transferase					2035:2045	O-linked N-acetylglucosamine transferase	2006:2045	O-linked N-acetylglucosamine transferase (Ogt)	2006:2051	Furthermore, the effects and mechanisms of the key genes of O-glycan sugar chain synthesis and hydrolases such as polypeptide N-acetylgalactosaminyltransferase1 (Galnt1), Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase (C1galt1), O-linked N-acetylglucosamine transferase (Ogt) and Hexosaminidase (Hex), were evaluated.
31604106	4	157	theme	O-glycosylation	575:589	arg1	effects					564:570	The effects	560:570	The effects of O-glycosylation on recombinant hCG protein expression	560:627	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	4	158	theme	chain	782:786	arg1	synthesis					788:796	O-glycan sugar chain synthesis	767:796	O-glycan sugar chain synthesis	767:796	The effects of O-glycosylation on recombinant hCG protein expression were assessed by adding O-glycan precursors and overexpressing and knocking down key regulatory genes of O-glycan precursor synthesis and O-glycan sugar chain synthesis or hydrolases.
31604106	14	159	theme	synergistic	2521:2531	arg1	effects					2533:2539	synergistic effects	2521:2539	synergistic effects	2521:2539	Overexpression of Ugp2 and Galnt1 simultaneously improved the recombinant hCG protein level by 2.44 times, and both had synergistic effects.
29988048	0	0	theme	coat	82:85	arg1	O-glycosylation					47:61	O-glycosylation	47:61	O-glycosylation of the VSG surface coat	47:85	African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
29988048	3	1	theme	variant	323:329	arg1	glycoprotein					339:350	its variant surface glycoprotein	319:350	its variant surface glycoprotein (VSG) coat	319:361	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	3	1	theme	variant	323:329	arg1	VSG					353:355	VSG	353:355	VSG	353:355	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	0	2	theme	surface	74:80	arg1	coat					82:85	the VSG surface coat	66:85	the VSG surface coat	66:85	African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
29988048	4	3	theme	immune	511:516	arg1	evasion					518:524	This persistent immune evasion	495:524	This persistent immune evasion	495:524	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
29988048	9	4	theme	parasite	1193:1200	arg1	virulence					1202:1210	parasite virulence	1193:1210	parasite virulence	1193:1210	We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity.
29988048	8	5	from	VSGs	1136:1139	arg1	present					1119:1125	present	1119:1125	present	1119:1125	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	4	6	theme	persistent	500:509	arg1	evasion					518:524	This persistent immune evasion	495:524	This persistent immune evasion	495:524	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
29988048	10	7	theme	post-translational	1417:1434	arg1	modifications					1436:1448	surface post-translational modifications	1409:1448	surface post-translational modifications	1409:1448	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	6	8	theme	VSG3	820:823	arg1	structure					795:803	The 1.4-Å-resolution crystal structure	766:803	The 1.4-Å-resolution crystal structure of the variant VSG3	766:823	The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state.
29988048	8	9	from	present	1119:1125	arg1	VSGs					1136:1139	other VSGs	1130:1139	other VSGs	1130:1139	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	5	10	theme	VSG	724:726	arg1	diversity					755:763	VSG structural and biochemical diversity	724:763	VSG structural and biochemical diversity	724:763	We establish here that this model does not account for the scope of VSG structural and biochemical diversity.
29988048	6	11	theme	variant	812:818	arg1	VSG3					820:823	the variant VSG3	808:823	the variant VSG3	808:823	The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state.
29988048	8	12	dep	three	1085:1089	arg1	to					1082:1083	to	1082:1083	to	1082:1083	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	4	13	theme	VSG	586:588	arg1	surface					590:596	the VSG surface	582:596	the VSG surface presented by a conserved underlying protein architecture	582:653	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
29988048	5	14	theme	structural	728:737	arg1	diversity					755:763	VSG structural and biochemical diversity	724:763	VSG structural and biochemical diversity	724:763	We establish here that this model does not account for the scope of VSG structural and biochemical diversity.
29988048	3	15	theme	distinct	480:487	arg1	VSGs					489:492	antigenically distinct VSGs	466:492	antigenically distinct VSGs	466:492	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	7	16	theme	VSG3	963:966	arg1	surface					952:958	the top surface	944:958	the top surface of VSG3	944:966	The structure also reveals an O-linked carbohydrate on the top surface of VSG3.
29988048	3	17	theme	VSG	432:434	arg1	repertoire					436:445	a large genetic VSG repertoire	416:445	a large genetic VSG repertoire	416:445	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	7	18	theme	top	948:950	arg1	surface					952:958	the top surface	944:958	the top surface of VSG3	944:966	The structure also reveals an O-linked carbohydrate on the top surface of VSG3.
29988048	10	19	theme	variation	1307:1315	arg1	paradigm					1285:1292	the paradigm	1281:1292	the paradigm of antigenic variation	1281:1315	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	3	20	theme	immune	375:380	arg1	clearance					382:390	immune clearance	375:390	immune clearance	375:390	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	3	21	theme	surface	331:337	arg1	glycoprotein					339:350	its variant surface glycoprotein	319:350	its variant surface glycoprotein (VSG) coat	319:361	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	3	21	theme	surface	331:337	arg1	VSG					353:355	VSG	353:355	VSG	353:355	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	0	22	theme	VSG	70:72	arg1	coat					82:85	the VSG surface coat	66:85	the VSG surface coat	66:85	African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
29988048	10	23	theme	antigenic	1297:1305	arg1	variation					1307:1315	antigenic variation	1297:1315	antigenic variation	1297:1315	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	3	24	theme	large	418:422	arg1	repertoire					436:445	a large genetic VSG repertoire	416:445	a large genetic VSG repertoire	416:445	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	0	25	theme	African	0:6	arg1	trypanosomes					8:19	African trypanosomes	0:19	African trypanosomes	0:19	African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
29988048	6	26	theme	crystal	787:793	arg1	structure					795:803	The 1.4-Å-resolution crystal structure	766:803	The 1.4-Å-resolution crystal structure of the variant VSG3	766:823	The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state.
29988048	6	27	theme	tertiary	853:860	arg1	fold					862:865	the tertiary fold	849:865	the tertiary fold	849:865	The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state.
29988048	3	28	theme	genetic	424:430	arg1	repertoire					436:445	a large genetic VSG repertoire	416:445	a large genetic VSG repertoire	416:445	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	0	29	theme	immune	27:32	arg1	clearance					34:42	immune clearance	27:42	immune clearance	27:42	African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
29988048	6	30	theme	1.4-Å-resolution	770:785	arg1	structure					795:803	The 1.4-Å-resolution crystal structure	766:803	The 1.4-Å-resolution crystal structure of the variant VSG3	766:823	The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state.
29988048	1	31	theme	African	92:98	arg1	brucei					124:129	The African trypanosome Trypanosoma brucei	88:129	The African trypanosome Trypanosoma brucei	88:129	The African trypanosome Trypanosoma brucei spp.
29988048	10	32	theme	immunomodulatory	1455:1470	arg1	impact					1472:1477	immunomodulatory impact	1455:1477	immunomodulatory impact	1455:1477	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	2	33	dep	molecules	219:227	arg1	evade					232:236	evade	232:236	to evade host immunity	229:250	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	3	34	theme	antibody-mediated	281:297	arg1	responses					306:314	robust antibody-mediated immune responses	274:314	robust antibody-mediated immune responses	274:314	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	9	35	theme	immunity	1254:1261	arg1	generation					1229:1238	the generation	1225:1238	the generation of protective immunity	1225:1261	We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity.
29988048	1	36	theme	trypanosome	100:110	arg1	brucei					124:129	The African trypanosome Trypanosoma brucei	88:129	The African trypanosome Trypanosoma brucei	88:129	The African trypanosome Trypanosoma brucei spp.
29988048	4	37	theme	underlying	623:632	arg1	architecture					642:653	a conserved underlying protein architecture	611:653	a conserved underlying protein architecture	611:653	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
29988048	4	38	theme	amino-acid	559:568	arg1	variance					570:577	amino-acid variance	559:577	amino-acid variance on the VSG surface presented by a conserved underlying protein architecture	559:653	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
29988048	6	39	theme	oligomeric	871:880	arg1	state					882:886	oligomeric state	871:886	oligomeric state	871:886	The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state.
29988048	8	40	theme	hexose	1091:1096	arg1	residues					1098:1105	zero to three hexose residues	1077:1105	zero to three hexose residues	1077:1105	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	10	41	theme	African	1324:1330	arg1	trypanosome					1332:1342	the African trypanosome	1320:1342	the African trypanosome	1320:1342	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	5	42	theme	biochemical	743:753	arg1	diversity					755:763	VSG structural and biochemical diversity	724:763	VSG structural and biochemical diversity	724:763	We establish here that this model does not account for the scope of VSG structural and biochemical diversity.
29988048	8	43	gly	O-glycosylation	1017:1031	arg2	site					1033:1036	this O-glycosylation site	1012:1036	this O-glycosylation site	1012:1036	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	8	44	located	present	1119:1125	arg1	VSGs					1136:1139	other VSGs	1130:1139	other VSGs	1130:1139	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	8	44	located	present	1119:1125	arg2	site					1033:1036	this O-glycosylation site	1012:1036	this O-glycosylation site	1012:1036	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	8	45	used	occupied	1057:1064	arg2	site					1033:1036	this O-glycosylation site	1012:1036	this O-glycosylation site	1012:1036	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	2	46	theme	antigenic	154:162	arg1	alteration					192:201	the orchestrated alteration	175:201	the orchestrated alteration of cell surface molecules to evade host immunity	175:250	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	2	46	theme	antigenic	154:162	arg1	variation					164:172	antigenic variation	154:172	antigenic variation	154:172	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	2	47	theme	molecules	219:227	arg1	alteration					192:201	the orchestrated alteration	175:201	the orchestrated alteration of cell surface molecules to evade host immunity	175:250	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	2	47	theme	molecules	219:227	arg1	variation					164:172	antigenic variation	154:172	antigenic variation	154:172	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	8	48	theme	other	1130:1134	arg1	VSGs					1136:1139	other VSGs	1130:1139	other VSGs	1130:1139	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	1	49	theme	Trypanosoma	112:122	arg1	brucei					124:129	The African trypanosome Trypanosoma brucei	88:129	The African trypanosome Trypanosoma brucei	88:129	The African trypanosome Trypanosoma brucei spp.
29988048	3	50	gly	glycoprotein	339:350	arg1	glycoprotein					339:350	its variant surface glycoprotein	319:350	its variant surface glycoprotein (VSG) coat	319:361	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	3	50	gly	glycoprotein	339:350	arg1	VSG					353:355	VSG	353:355	VSG	353:355	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	2	51	theme	cell	206:209	arg1	molecules					219:227	cell surface molecules	206:227	cell surface molecules to evade host immunity	206:250	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	2	52	theme	surface	211:217	arg1	molecules					219:227	cell surface molecules	206:227	cell surface molecules to evade host immunity	206:250	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	7	53	theme	O-linked	919:926	arg1	carbohydrate					928:939	an O-linked carbohydrate	916:939	an O-linked carbohydrate	916:939	The structure also reveals an O-linked carbohydrate on the top surface of VSG3.
29988048	9	54	theme	protective	1243:1252	arg1	immunity					1254:1261	protective immunity	1243:1261	protective immunity	1243:1261	We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity.
29988048	3	55	theme	immune	299:304	arg1	responses					306:314	robust antibody-mediated immune responses	274:314	robust antibody-mediated immune responses	274:314	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	8	56	theme	O-glycosylation	1017:1031	arg1	site					1033:1036	this O-glycosylation site	1012:1036	this O-glycosylation site	1012:1036	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	8	57	theme	spectrometric	974:986	arg1	analysis					988:995	Mass spectrometric analysis	969:995	Mass spectrometric analysis	969:995	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	10	58	theme	VSG	1355:1357	arg1	variability					1359:1369	VSG variability	1355:1369	VSG variability beyond amino-acid sequence	1355:1396	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	7	59	link	O-linked	919:926	arg1	carbohydrate					928:939	an O-linked carbohydrate	916:939	an O-linked carbohydrate	916:939	The structure also reveals an O-linked carbohydrate on the top surface of VSG3.
29988048	10	60	theme	amino-acid	1378:1387	arg1	sequence					1389:1396	amino-acid sequence	1378:1396	amino-acid sequence	1378:1396	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	10	61	theme	surface	1409:1415	arg1	modifications					1436:1448	surface post-translational modifications	1409:1448	surface post-translational modifications	1409:1448	These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.
29988048	8	62	attach	present	1119:1125	arg1	VSGs					1136:1139	other VSGs	1130:1139	other VSGs	1130:1139	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	8	62	attach	present	1119:1125	arg2	site					1033:1036	this O-glycosylation site	1012:1036	this O-glycosylation site	1012:1036	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	3	63	theme	glycoprotein	339:350	arg1	coat					358:361	its variant surface glycoprotein (VSG) coat	319:361	its variant surface glycoprotein (VSG) coat	319:361	The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs.
29988048	2	64	theme	orchestrated	179:190	arg1	alteration					192:201	the orchestrated alteration	175:201	the orchestrated alteration of cell surface molecules to evade host immunity	175:250	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	2	64	theme	orchestrated	179:190	arg1	variation					164:172	antigenic variation	154:172	antigenic variation	154:172	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	0	65	gly	O-glycosylation	47:61	arg1	coat					82:85	the VSG surface coat	66:85	the VSG surface coat	66:85	African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
29988048	4	66	theme	protein	634:640	arg1	architecture					642:653	a conserved underlying protein architecture	611:653	a conserved underlying protein architecture	611:653	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
29988048	4	67	theme	conserved	613:621	arg1	architecture					642:653	a conserved underlying protein architecture	611:653	a conserved underlying protein architecture	611:653	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
29988048	5	68	theme	diversity	755:763	arg1	scope					715:719	the scope	711:719	the scope of VSG structural and biochemical diversity	711:763	We establish here that this model does not account for the scope of VSG structural and biochemical diversity.
29988048	2	69	theme	host	238:241	arg1	immunity					243:250	host immunity	238:250	host immunity	238:250	is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity.
29988048	8	70	theme	Mass	969:972	arg1	analysis					988:995	Mass spectrometric analysis	969:995	Mass spectrometric analysis	969:995	Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs.
29988048	4	71	from	variance	570:577	arg1	surface					590:596	the VSG surface	582:596	the VSG surface presented by a conserved underlying protein architecture	582:653	This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture.
31151453	10	0	theme	MGU	1958:1960	arg1	levels					1975:1980	MGU and O-GlcNAc levels	1958:1980	MGU and O-GlcNAc levels	1958:1980	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	2	1	theme	activated	399:407	arg1	cardioprotection					409:424	exogenously activated cardioprotection	387:424	exogenously activated cardioprotection by ischemic preconditioning (IPC)	387:458	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	5	2	theme	2 × 5 min	1131:1139	arg1	cycles					1141:1146	2 × 5 min cycles	1131:1146	2 × 5 min cycles	1131:1146	IPC (2 × 5 min cycles) reduced IS during normo- (p < 0.01 for both groups) but not during hyperglycemia independently of the presence of T2DM.
31151453	5	2	theme	2 × 5 min	1131:1139	arg1	IPC					1126:1128	IPC	1126:1128	IPC (2 × 5 min cycles)	1126:1147	IPC (2 × 5 min cycles) reduced IS during normo- (p < 0.01 for both groups) but not during hyperglycemia independently of the presence of T2DM.
31151453	1	3	theme	reduced	301:307	arg1	capacity					309:316	reduced capacity	301:316	reduced capacity for cardioprotection	301:337	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	3	4	from	METHODS	695:701	arg1	hearts					741:746	isolated, perfused rat hearts	718:746	isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS)	718:799	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	2	5	theme	O-linked	652:659	arg1	O-GlcNAc					684:691	O-GlcNAc	684:691	O-GlcNAc	684:691	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	5	theme	O-linked	652:659	arg1	β-N-acetylglucosamine					661:681	myocardial O-linked β-N-acetylglucosamine	641:681	myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	641:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	10	6	theme	O-GlcNAc	1966:1973	arg1	levels					1975:1980	MGU and O-GlcNAc levels	1958:1980	MGU and O-GlcNAc levels	1958:1980	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	6	7	with	animals	1369:1375	arg1	p < 0.05					1388:1395	p < 0.05	1388:1395	p < 0.05	1388:1395	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	6	7	with	animals	1369:1375	arg1	T2DM					1382:1385	T2DM	1382:1385	T2DM (p < 0.05)	1382:1396	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	0	8	with	rats	118:121	arg1	diabetes					135:142	type 2 diabetes	128:142	type 2 diabetes	128:142	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	10	9	theme	induced	2011:2017	arg1	cardioprotection					2019:2034	exogenously induced cardioprotection	1999:2034	exogenously induced cardioprotection	1999:2034	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	3	10	theme	infarct	783:789	arg1	ischemia-reperfusion					761:780	ischemia-reperfusion	761:780	ischemia-reperfusion	761:780	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	3	10	theme	infarct	783:789	arg1	size					791:794	infarct size	783:794	infarct size (IS)	783:799	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	5	11	dep	normo-	1167:1172	arg1	p < 0.01					1175:1182	p < 0.01	1175:1182	p < 0.01 for both groups	1175:1198	IPC (2 × 5 min cycles) reduced IS during normo- (p < 0.01 for both groups) but not during hyperglycemia independently of the presence of T2DM.
31151453	2	12	theme	uptake	624:629	arg1	involvement					590:600	the involvement	586:600	the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	586:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	12	theme	uptake	624:629	arg1	mechanism					571:579	an inherent mechanism	559:579	an inherent mechanism	559:579	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	4	13	from	n = 8	1038:1042	arg1	group					1052:1056	each group	1047:1056	each group	1047:1056	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	9	14	theme	exogenous	1910:1918	arg1	cardioprotection					1920:1935	exogenous cardioprotection	1910:1935	exogenous cardioprotection by IPC	1910:1942	CONCLUSION While the effect of IPC is reduced during hyperglycemia in rats without T2DM, endogenous cardioprotection in animals with T2DM is not influenced by hyperglycemia and the capacity for exogenous cardioprotection by IPC is preserved.
31151453	2	15	theme	myocardial	605:614	arg1	MGU					632:634	MGU	632:634	MGU	632:634	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	15	theme	myocardial	605:614	arg1	uptake					624:629	myocardial glucose uptake	605:629	myocardial glucose uptake (MGU)	605:635	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	6	16	theme	IPC	1306:1308	arg1	cycles					1330:1335	4 × 5 min cycles	1320:1335	4 × 5 min cycles	1320:1335	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	6	16	theme	IPC	1306:1308	arg1	stimulus					1310:1317	an intensified IPC stimulus	1291:1317	an intensified IPC stimulus (4 × 5 min cycles) reduced	1291:1344	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	1	17	from	mortality	192:200	arg1	patients					205:212	patients	205:212	patients with diabetes and admission hyperglycemia after an acute coronary syndrome	205:287	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	4	18	theme	recent	978:983	arg1	fa/fa					997:1001	fa/fa	997:1001	fa/fa	997:1001	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	4	18	theme	recent	978:983	arg1	T2DM					991:994	recent onset T2DM	978:994	recent onset T2DM (fa/fa)	978:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	8	19	from	animals	1697:1703	arg1	hearts					1685:1690	hearts	1685:1690	hearts from animals with T2DM	1685:1713	Intensified IPC at hyperglycemia increased MGU (p < 0.05) and O-GlcNAc levels (p < 0.05) only in hearts from animals with T2DM.
31151453	1	20	theme	increased	182:190	arg1	mortality					192:200	increased mortality	182:200	increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome	182:287	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	2	21	from	impact	360:365	arg1	cardioprotection					409:424	exogenously activated cardioprotection	387:424	exogenously activated cardioprotection by ischemic preconditioning (IPC)	387:458	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	4	22	theme	old	942:944	arg1	rats					968:971	12-week old Zucker diabetic fatty rats	934:971	12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa)	934:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	0	23	from	Impact	0:5	arg1	susceptibility					59:72	myocardial ischemia-reperfusion susceptibility	27:72	myocardial ischemia-reperfusion susceptibility	27:72	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	0	23	from	Impact	0:5	arg1	preconditioning					87:101	ischemic preconditioning	78:101	ischemic preconditioning	78:101	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	4	24	dep	smaller	923:929	arg1	rats					1012:1015	rats	1012:1015	rats without T2DM (fa/+) (n = 8 in each group)	1012:1057	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	7	25	dep	normoglycemia	1492:1504	arg1	MGU					1507:1509	MGU	1507:1509	MGU	1507:1509	IPC increased MGU and O-GlcNAc levels during reperfusion in animals with and without T2DM at normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01 for both groups) but not during hyperglycemia.
31151453	7	25	dep	normoglycemia	1492:1504	arg1	O-GlcNAc					1522:1529	O-GlcNAc	1522:1529	O-GlcNAc	1522:1529	IPC increased MGU and O-GlcNAc levels during reperfusion in animals with and without T2DM at normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01 for both groups) but not during hyperglycemia.
31151453	4	26	dep	T2DM	1025:1028	arg1	n = 8					1038:1042	n = 8	1038:1042	n = 8 in each group	1038:1056	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	4	27	theme	diabetic	953:960	arg1	rats					968:971	12-week old Zucker diabetic fatty rats	934:971	12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa)	934:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	0	28	from	susceptibility	59:72	arg1	rats					118:121	rats	118:121	rats with type 2 diabetes	118:142	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	0	28	from	susceptibility	59:72	arg1	hearts					106:111	hearts	106:111	hearts from rats with type 2 diabetes	106:142	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	5	29	theme	presence	1251:1258	arg1	hyperglycemia					1216:1228	hyperglycemia	1216:1228	hyperglycemia independently of the presence of T2DM	1216:1266	IPC (2 × 5 min cycles) reduced IS during normo- (p < 0.01 for both groups) but not during hyperglycemia independently of the presence of T2DM.
31151453	3	30	dep	isolated	718:725	arg1	perfused					728:735	perfused	728:735	perfused	728:735	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	7	31	dep	MGU	1507:1509	arg1	p < 0.01					1532:1539	p < 0.01	1532:1539	p < 0.01	1532:1539	IPC increased MGU and O-GlcNAc levels during reperfusion in animals with and without T2DM at normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01 for both groups) but not during hyperglycemia.
31151453	7	31	dep	MGU	1507:1509	arg1	p < 0.05					1512:1519	p < 0.05	1512:1519	p < 0.05	1512:1519	IPC increased MGU and O-GlcNAc levels during reperfusion in animals with and without T2DM at normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01 for both groups) but not during hyperglycemia.
31151453	2	32	theme	diabetes	492:499	arg1	T2DM					511:514	T2DM	511:514	T2DM	511:514	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	32	theme	diabetes	492:499	arg1	mellitus					501:508	type 2 diabetes mellitus	485:508	type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	485:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	5	33	theme	T2DM	1263:1266	arg1	presence					1251:1258	the presence	1247:1258	the presence of T2DM	1247:1266	IPC (2 × 5 min cycles) reduced IS during normo- (p < 0.01 for both groups) but not during hyperglycemia independently of the presence of T2DM.
31151453	2	34	theme	type	485:488	arg1	T2DM					511:514	T2DM	511:514	T2DM	511:514	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	34	theme	type	485:488	arg1	mellitus					501:508	type 2 diabetes mellitus	485:508	type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	485:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	10	35	theme	different	2114:2122	arg1	mechanisms					2135:2144	different underlying mechanisms	2114:2144	different underlying mechanisms	2114:2144	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	0	36	theme	hyperglycemia	10:22	arg1	Impact					0:5	Impact	0:5	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.	0:143	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	0	37	theme	myocardial	27:36	arg1	susceptibility					59:72	myocardial ischemia-reperfusion susceptibility	27:72	myocardial ischemia-reperfusion susceptibility	27:72	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	9	38	from	cardioprotection	1816:1831	arg1	animals					1836:1842	animals	1836:1842	animals with T2DM	1836:1852	CONCLUSION While the effect of IPC is reduced during hyperglycemia in rats without T2DM, endogenous cardioprotection in animals with T2DM is not influenced by hyperglycemia and the capacity for exogenous cardioprotection by IPC is preserved.
31151453	0	39	theme	ischemic	78:85	arg1	preconditioning					87:101	ischemic preconditioning	78:101	ischemic preconditioning	78:101	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	4	40	with	rats	968:971	arg1	fa/fa					997:1001	fa/fa	997:1001	fa/fa	997:1001	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	4	40	with	rats	968:971	arg1	T2DM					991:994	recent onset T2DM	978:994	recent onset T2DM (fa/fa)	978:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	3	41	theme	isolated	718:725	arg1	hearts					741:746	isolated, perfused rat hearts	718:746	isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS)	718:799	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	2	42	theme	hyperglycemia	370:382	arg1	impact					360:365	the impact	356:365	the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC)	356:458	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	8	43	from	hyperglycemia	1607:1619	arg1	IPC					1600:1602	Intensified IPC	1588:1602	Intensified IPC at hyperglycemia	1588:1619	Intensified IPC at hyperglycemia increased MGU (p < 0.05) and O-GlcNAc levels (p < 0.05) only in hearts from animals with T2DM.
31151453	2	44	theme	ischemic	429:436	arg1	IPC					455:457	IPC	455:457	IPC	455:457	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	44	theme	ischemic	429:436	arg1	preconditioning					438:452	ischemic preconditioning	429:452	ischemic preconditioning (IPC)	429:458	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	1	45	theme	acute	265:269	arg1	syndrome					280:287	an acute coronary syndrome	262:287	an acute coronary syndrome	262:287	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	6	46	from	animals	1369:1375	arg1	hearts					1357:1362	hearts	1357:1362	hearts from animals with T2DM (p < 0.05)	1357:1396	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	2	47	from	rats	475:478	arg1	hearts					463:468	hearts	463:468	hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	463:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	48	link	O-linked	652:659	arg1	O-GlcNAc					684:691	O-GlcNAc	684:691	O-GlcNAc	684:691	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	48	link	O-linked	652:659	arg1	β-N-acetylglucosamine					661:681	myocardial O-linked β-N-acetylglucosamine	641:681	myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	641:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	10	49	theme	endogenous	2163:2172	arg1	cardioprotection					2174:2189	exogenous and endogenous cardioprotection	2149:2189	exogenous and endogenous cardioprotection	2149:2189	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	9	50	theme	IPC	1747:1749	arg1	effect					1737:1742	the effect	1733:1742	the effect of IPC	1733:1749	CONCLUSION While the effect of IPC is reduced during hyperglycemia in rats without T2DM, endogenous cardioprotection in animals with T2DM is not influenced by hyperglycemia and the capacity for exogenous cardioprotection by IPC is preserved.
31151453	10	51	theme	exogenous	2149:2157	arg1	cardioprotection					2174:2189	exogenous and endogenous cardioprotection	2149:2189	exogenous and endogenous cardioprotection	2149:2189	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	8	52	with	animals	1697:1703	arg1	T2DM					1710:1713	T2DM	1710:1713	T2DM	1710:1713	Intensified IPC at hyperglycemia increased MGU (p < 0.05) and O-GlcNAc levels (p < 0.05) only in hearts from animals with T2DM.
31151453	4	53	dep	rats	1012:1015	arg1	both					1059:1062	both	1059:1062	both	1059:1062	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	2	54	with	rats	475:478	arg1	T2DM					511:514	T2DM	511:514	T2DM	511:514	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	54	with	rats	475:478	arg1	mellitus					501:508	type 2 diabetes mellitus	485:508	type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	485:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	55	theme	β-N-acetylglucosamine	661:681	arg1	involvement					590:600	the involvement	586:600	the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	586:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	55	theme	β-N-acetylglucosamine	661:681	arg1	mechanism					571:579	an inherent mechanism	559:579	an inherent mechanism	559:579	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	8	56	theme	Intensified	1588:1598	arg1	IPC					1600:1602	Intensified IPC	1588:1602	Intensified IPC at hyperglycemia	1588:1619	Intensified IPC at hyperglycemia increased MGU (p < 0.05) and O-GlcNAc levels (p < 0.05) only in hearts from animals with T2DM.
31151453	2	57	theme	myocardial	641:650	arg1	O-GlcNAc					684:691	O-GlcNAc	684:691	O-GlcNAc	684:691	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	57	theme	myocardial	641:650	arg1	β-N-acetylglucosamine					661:681	myocardial O-linked β-N-acetylglucosamine	641:681	myocardial O-linked β-N-acetylglucosamine (O-GlcNAc)	641:692	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	0	58	from	preconditioning	87:101	arg1	rats					118:121	rats	118:121	rats with type 2 diabetes	118:142	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	0	58	from	preconditioning	87:101	arg1	hearts					106:111	hearts	106:111	hearts from rats with type 2 diabetes	106:142	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	9	59	theme	endogenous	1805:1814	arg1	cardioprotection					1816:1831	endogenous cardioprotection	1805:1831	endogenous cardioprotection in animals with T2DM	1805:1852	CONCLUSION While the effect of IPC is reduced during hyperglycemia in rats without T2DM, endogenous cardioprotection in animals with T2DM is not influenced by hyperglycemia and the capacity for exogenous cardioprotection by IPC is preserved.
31151453	3	60	dep	[Glucose	835:842	arg1	 = 22 mmol/L					844:855	 = 22 mmol/L	844:855	 = 22 mmol/L	844:855	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	2	61	theme	glucose	616:622	arg1	MGU					632:634	MGU	632:634	MGU	632:634	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	2	61	theme	glucose	616:622	arg1	uptake					624:629	myocardial glucose uptake	605:629	myocardial glucose uptake (MGU)	605:635	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	0	62	from	rats	118:121	arg1	hearts					106:111	hearts	106:111	hearts from rats with type 2 diabetes	106:142	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	0	62	from	rats	118:121	arg1	susceptibility					59:72	myocardial ischemia-reperfusion susceptibility	27:72	myocardial ischemia-reperfusion susceptibility	27:72	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	0	62	from	rats	118:121	arg1	preconditioning					87:101	ischemic preconditioning	78:101	ischemic preconditioning	78:101	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	8	63	theme	O-GlcNAc	1650:1657	arg1	levels					1659:1664	O-GlcNAc levels	1650:1664	O-GlcNAc levels (p < 0.05)	1650:1675	Intensified IPC at hyperglycemia increased MGU (p < 0.05) and O-GlcNAc levels (p < 0.05) only in hearts from animals with T2DM.
31151453	8	63	theme	O-GlcNAc	1650:1657	arg1	p < 0.05					1667:1674	p < 0.05	1667:1674	p < 0.05	1667:1674	Intensified IPC at hyperglycemia increased MGU (p < 0.05) and O-GlcNAc levels (p < 0.05) only in hearts from animals with T2DM.
31151453	10	64	with	animals	2085:2091	arg1	T2DM					2098:2101	T2DM	2098:2101	T2DM	2098:2101	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	4	65	theme	fatty	962:966	arg1	rats					968:971	12-week old Zucker diabetic fatty rats	934:971	12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa)	934:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	10	66	theme	endogenous	2054:2063	arg1	cardioprotection					2065:2080	endogenous cardioprotection	2054:2080	endogenous cardioprotection	2054:2080	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	4	67	theme	12-week	934:940	arg1	rats					968:971	12-week old Zucker diabetic fatty rats	934:971	12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa)	934:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	6	68	theme	intensified	1294:1304	arg1	cycles					1330:1335	4 × 5 min cycles	1320:1335	4 × 5 min cycles	1320:1335	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	6	68	theme	intensified	1294:1304	arg1	stimulus					1310:1317	an intensified IPC stimulus	1291:1317	an intensified IPC stimulus (4 × 5 min cycles) reduced	1291:1344	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	3	69	dep	size	791:794	arg1	IS					797:798	IS	797:798	IS	797:798	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	9	70	with	animals	1836:1842	arg1	T2DM					1849:1852	T2DM	1849:1852	T2DM	1849:1852	CONCLUSION While the effect of IPC is reduced during hyperglycemia in rats without T2DM, endogenous cardioprotection in animals with T2DM is not influenced by hyperglycemia and the capacity for exogenous cardioprotection by IPC is preserved.
31151453	2	71	theme	inherent	562:569	arg1	mechanism					571:579	an inherent mechanism	559:579	an inherent mechanism	559:579	We investigated the impact of hyperglycemia on exogenously activated cardioprotection by ischemic preconditioning (IPC) in hearts from rats with type 2 diabetes mellitus (T2DM) that were endogenously cardioprotected by an inherent mechanism, and the involvement of myocardial glucose uptake (MGU) and myocardial O-linked β-N-acetylglucosamine (O-GlcNAc).
31151453	1	72	dep	BACKGROUND	145:154	arg1	involve					293:299	involve	293:299	may involve reduced capacity for cardioprotection	289:337	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	0	73	theme	type	128:131	arg1	diabetes					135:142	type 2 diabetes	128:142	type 2 diabetes	128:142	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	3	74	dep	[Glucose	879:886	arg1	 = 11 mmol/L					888:899	 = 11 mmol/L	888:899	 = 11 mmol/L	888:899	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	4	75	theme	Zucker	946:951	arg1	rats					968:971	12-week old Zucker diabetic fatty rats	934:971	12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa)	934:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	10	76	theme	underlying	2124:2133	arg1	mechanisms					2135:2144	different underlying mechanisms	2114:2144	different underlying mechanisms	2114:2144	MGU and O-GlcNAc levels are increased by exogenously induced cardioprotection by IPC but not by endogenous cardioprotection in animals with T2DM reflecting different underlying mechanisms by exogenous and endogenous cardioprotection.
31151453	1	77	dep	diabetes	219:226	arg1	hyperglycemia					242:254	hyperglycemia	242:254	hyperglycemia	242:254	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	0	78	theme	ischemia-reperfusion	38:57	arg1	susceptibility					59:72	myocardial ischemia-reperfusion susceptibility	27:72	myocardial ischemia-reperfusion susceptibility	27:72	Impact of hyperglycemia on myocardial ischemia-reperfusion susceptibility and ischemic preconditioning in hearts from rats with type 2 diabetes.
31151453	4	79	theme	onset	985:989	arg1	fa/fa					997:1001	fa/fa	997:1001	fa/fa	997:1001	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	4	79	theme	onset	985:989	arg1	T2DM					991:994	recent onset T2DM	978:994	recent onset T2DM (fa/fa)	978:1002	IS was smaller in 12-week old Zucker diabetic fatty rats with recent onset T2DM (fa/fa) than in rats without T2DM (fa/+) (n = 8 in each group) both during hyperglycemia (p < 0.05) and normoglycemia (p < 0.05).
31151453	6	80	theme	4 × 5 min	1320:1328	arg1	cycles					1330:1335	4 × 5 min cycles	1320:1335	4 × 5 min cycles	1320:1335	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	6	80	theme	4 × 5 min	1320:1328	arg1	stimulus					1310:1317	an intensified IPC stimulus	1291:1317	an intensified IPC stimulus (4 × 5 min cycles) reduced	1291:1344	During hyperglycemia, an intensified IPC stimulus (4 × 5 min cycles) reduced IS only in hearts from animals with T2DM (p < 0.05).
31151453	1	81	with	patients	205:212	arg1	admission					232:240	admission	232:240	admission	232:240	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	1	81	with	patients	205:212	arg1	diabetes					219:226	diabetes	219:226	diabetes	219:226	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
31151453	7	82	theme	O-GlcNAc	1421:1428	arg1	levels					1430:1435	MGU and O-GlcNAc levels	1413:1435	MGU and O-GlcNAc levels	1413:1435	IPC increased MGU and O-GlcNAc levels during reperfusion in animals with and without T2DM at normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01 for both groups) but not during hyperglycemia.
31151453	7	83	theme	MGU	1413:1415	arg1	levels					1430:1435	MGU and O-GlcNAc levels	1413:1435	MGU and O-GlcNAc levels	1413:1435	IPC increased MGU and O-GlcNAc levels during reperfusion in animals with and without T2DM at normoglycemia (MGU: p < 0.05, O-GlcNAc: p < 0.01 for both groups) but not during hyperglycemia.
31151453	3	84	from	RESULTS	707:713	arg1	hearts					741:746	isolated, perfused rat hearts	718:746	isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS)	718:799	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	3	85	theme	rat	737:739	arg1	hearts					741:746	isolated, perfused rat hearts	718:746	isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS)	718:799	METHODS AND RESULTS In isolated, perfused rat hearts subjected to ischemia-reperfusion, infarct size (IS) was overall larger during hyper- ([Glucose] = 22 mmol/L]) than normoglycemia ([Glucose] = 11 mmol/L]) (p < 0.001).
31151453	1	86	theme	coronary	271:278	arg1	syndrome					280:287	an acute coronary syndrome	262:287	an acute coronary syndrome	262:287	BACKGROUND The mechanisms underlying increased mortality in patients with diabetes and admission hyperglycemia after an acute coronary syndrome may involve reduced capacity for cardioprotection.
29708979	4	0	from	tumorigenicity	621:634	arg1	types					647:651	diverse types	639:651	diverse types of cancers	639:662	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	5	1	dep	fate	707:710	arg1	the					703:705	the	703:705	the	703:705	However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell.
29708979	6	2	theme	retained	860:867	arg1	region					883:888	the retained juxtamembrane region	856:888	the retained juxtamembrane region of MUC16	856:897	Herein, we characterize two monoclonal antibodies (mAbs) showing specificity to the retained juxtamembrane region of MUC16.
29708979	0	3	theme	MUC16	102:106	arg1	cleavage					108:115	MUC16 cleavage	102:115	MUC16 cleavage in human ovarian cancer	102:139	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	4	4	theme	retained	540:547	arg1	CT					567:568	CT	567:568	CT	567:568	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	4	4	theme	retained	540:547	arg1	fragment					571:578	the retained carboxy-terminal (CT) fragment	536:578	the retained carboxy-terminal (CT) fragment of MUC16	536:587	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	12	5	theme	MUC16	1700:1704	arg1	cleavage					1706:1713	MUC16 cleavage	1700:1713	MUC16 cleavage	1700:1713	These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
29708979	6	6	theme	monoclonal	804:813	arg1	mAbs					827:830	mAbs	827:830	mAbs	827:830	Herein, we characterize two monoclonal antibodies (mAbs) showing specificity to the retained juxtamembrane region of MUC16.
29708979	6	6	theme	monoclonal	804:813	arg1	antibodies					815:824	two monoclonal antibodies	800:824	two monoclonal antibodies (mAbs) showing specificity to the retained juxtamembrane region of MUC16	800:897	Herein, we characterize two monoclonal antibodies (mAbs) showing specificity to the retained juxtamembrane region of MUC16.
29708979	2	7	from	present	369:375	arg1	antigen					387:393	cancer antigen 125 (CA125)	380:405	cancer antigen 125 (CA125)	380:405	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	0	8	theme	human	120:124	arg1	cancer					134:139	human ovarian cancer	120:139	human ovarian cancer	120:139	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	6	9	theme	MUC16	893:897	arg1	region					883:888	the retained juxtamembrane region	856:888	the retained juxtamembrane region of MUC16	856:897	Herein, we characterize two monoclonal antibodies (mAbs) showing specificity to the retained juxtamembrane region of MUC16.
29708979	5	10	theme	limited	674:680	arg1	data					682:685	limited data	674:685	limited data	674:685	However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell.
29708979	2	11	theme	N-terminal	331:340	arg1	epitopes					360:367	the N-terminal tandemly repeated epitopes	327:367	the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125)	327:405	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	9	12	theme	total	1303:1307	arg1	cases					1324:1328	total ovarian cancer cases	1303:1328	total ovarian cancer cases	1303:1328	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	5	13	theme	fragment	732:739	arg1	existence					716:724	existence	716:724	existence	716:724	However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell.
29708979	5	13	theme	fragment	732:739	arg1	fate					707:710	fate	707:710	fate	707:710	However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell.
29708979	4	14	theme	Recent	501:506	arg1	reports					508:514	Recent reports	501:514	Recent reports	501:514	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	4	15	theme	important	603:611	arg1	role					613:616	an important role	600:616	an important role	600:616	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	8	16	theme	tumor	1136:1140	arg1	tissues					1142:1148	ovarian tumor tissues	1128:1148	ovarian tumor tissues	1128:1148	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	11	17	theme	CT	1469:1470	arg1	s					1476:1476	The CT mAb(s)	1465:1477	The CT mAb(s)	1465:1477	The CT mAb(s) accurately predict expression of MUC16 since their epitopes are not tandemly repeated and their reactivity may not be dependent on O-linked glycosylation.
29708979	10	18	theme	papillary	1353:1361	arg1	cases					1363:1367	serous and serous papillary cases	1335:1367	serous and serous papillary cases	1335:1367	For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%).
29708979	2	19	from	antigen	387:393	arg1	present					369:375	present	369:375	present	369:375	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	9	20	theme	ovarian	1309:1315	arg1	cases					1324:1328	total ovarian cancer cases	1303:1328	total ovarian cancer cases	1303:1328	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	12	21	theme	valuable	1664:1671	arg1	reagents					1673:1680	valuable reagents	1664:1680	valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer	1664:1796	These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
29708979	12	21	theme	valuable	1664:1671	arg1	antibodies					1640:1649	These antibodies	1634:1649	These antibodies	1634:1649	These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
29708979	9	22	theme	cancer	1317:1322	arg1	cases					1324:1328	total ovarian cancer cases	1303:1328	total ovarian cancer cases	1303:1328	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	0	23	theme	ovarian	126:132	arg1	cancer					134:139	human ovarian cancer	120:139	human ovarian cancer	120:139	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	6	24	theme	juxtamembrane	869:881	arg1	region					883:888	the retained juxtamembrane region	856:888	the retained juxtamembrane region of MUC16	856:897	Herein, we characterize two monoclonal antibodies (mAbs) showing specificity to the retained juxtamembrane region of MUC16.
29708979	5	25	theme	cell	770:773	arg1	surface					748:754	the surface	744:754	the surface of the cancer cell	744:773	However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell.
29708979	11	26	theme	MUC16	1512:1516	arg1	expression					1498:1507	expression	1498:1507	expression of MUC16	1498:1516	The CT mAb(s) accurately predict expression of MUC16 since their epitopes are not tandemly repeated and their reactivity may not be dependent on O-linked glycosylation.
29708979	12	27	theme	therapeutic	1747:1757	arg1	agents					1759:1764	potential therapeutic agents	1737:1764	potential therapeutic agents for treatment of ovarian cancer	1737:1796	These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
29708979	7	28	dep	NIH	982:984	arg1	[OVCAR-3					994:1001	OVCAR-3 [OVCAR-3]	986:1002	NIH:OVCAR-3 [OVCAR-3]	982:1002	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	1	29	theme	important	193:201	arg1	roles					203:207	important roles	193:207	important roles	193:207	MUC16 is overexpressed in ovarian cancer and plays important roles in invasion and metastasis.
29708979	12	30	theme	ovarian	1783:1789	arg1	cancer					1791:1796	ovarian cancer	1783:1796	ovarian cancer	1783:1796	These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
29708979	5	31	theme	cancer	763:768	arg1	cell					770:773	the cancer cell	759:773	the cancer cell	759:773	However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell.
29708979	7	32	theme	MUC16	1026:1030	arg1	subunits					1032:1039	the cleaved MUC16 subunits	1014:1039	the cleaved MUC16 subunits	1014:1039	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	2	33	theme	present	369:375	arg1	epitopes					360:367	the N-terminal tandemly repeated epitopes	327:367	the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125)	327:405	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	12	34	theme	potential	1737:1745	arg1	agents					1759:1764	potential therapeutic agents	1737:1764	potential therapeutic agents for treatment of ovarian cancer	1737:1796	These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
29708979	8	35	theme	tissues	1142:1148	arg1	grades					1118:1123	different grades	1108:1123	different grades of ovarian tumor tissues	1108:1148	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	8	36	theme	ovarian	1128:1134	arg1	tissues					1142:1148	ovarian tumor tissues	1128:1148	ovarian tumor tissues	1128:1148	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	10	37	theme	serous	1335:1340	arg1	cases					1363:1367	serous and serous papillary cases	1335:1367	serous and serous papillary cases	1335:1367	For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%).
29708979	7	38	theme	first	908:912	arg1	time					914:917	the first time	904:917	the first time	904:917	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	5	39	theme	CT	729:730	arg1	fragment					732:739	CT fragment	729:739	CT fragment	729:739	However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell.
29708979	10	40	theme	CT	1423:1424	arg1	mAb					1426:1428	CT mAb	1423:1428	CT mAb (5E6)	1423:1434	For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%).
29708979	10	40	theme	CT	1423:1424	arg1	5E6					1431:1433	5E6	1431:1433	5E6	1431:1433	For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%).
29708979	2	41	attach	present	369:375	arg1	antigen					387:393	cancer antigen 125 (CA125)	380:405	cancer antigen 125 (CA125)	380:405	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	2	41	attach	present	369:375	arg2	epitopes					360:367	the N-terminal tandemly repeated epitopes	327:367	the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125)	327:405	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	10	42	theme	CA125	1374:1378	arg1	mAb					1386:1388	the CA125 (M11) mAb	1370:1388	the CA125 (M11) mAb	1370:1388	For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%).
29708979	2	43	theme	repeated	351:358	arg1	epitopes					360:367	the N-terminal tandemly repeated epitopes	327:367	the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125)	327:405	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	3	44	theme	extracellular	480:492	arg1	space					494:498	the extracellular space	476:498	the extracellular space	476:498	MUC16 is cleaved at a specific location, thus, releasing CA125 into the extracellular space.
29708979	8	45	theme	differential	1160:1171	arg1	reactivity					1173:1182	differential reactivity	1160:1182	differential reactivity of CA125 and MUC16 CT mAbs	1160:1209	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	9	46	theme	CT	1264:1265	arg1	5E6					1272:1274	the CT mAb (5E6)	1260:1275	the CT mAb (5E6)	1260:1275	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	7	47	theme	cleaved	1018:1024	arg1	subunits					1032:1039	the cleaved MUC16 subunits	1014:1039	the cleaved MUC16 subunits	1014:1039	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	0	48	from	cleavage	108:115	arg1	cancer					134:139	human ovarian cancer	120:139	human ovarian cancer	120:139	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	9	49	theme	mAb	1267:1269	arg1	5E6					1272:1274	the CT mAb (5E6)	1260:1275	the CT mAb (5E6)	1260:1275	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	0	50	theme	specific	53:60	arg1	antibodies					73:82	carboxy-terminus specific monoclonal antibodies	36:82	carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer	36:139	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	4	51	theme	MUC16	583:587	arg1	CT					567:568	CT	567:568	CT	567:568	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	4	51	theme	MUC16	583:587	arg1	fragment					571:578	the retained carboxy-terminal (CT) fragment	536:578	the retained carboxy-terminal (CT) fragment of MUC16	536:587	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	8	52	dep	CA125	1187:1191	arg1	mAbs					1206:1209	CT mAbs	1203:1209	CT mAbs	1203:1209	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	11	53	theme	mAb	1472:1474	arg1	s					1476:1476	The CT mAb(s)	1465:1477	The CT mAb(s)	1465:1477	The CT mAb(s) accurately predict expression of MUC16 since their epitopes are not tandemly repeated and their reactivity may not be dependent on O-linked glycosylation.
29708979	0	54	theme	carboxy-terminus	36:51	arg1	antibodies					73:82	carboxy-terminus specific monoclonal antibodies	36:82	carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer	36:139	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	8	55	from	analyses	1096:1103	arg1	grades					1118:1123	different grades	1108:1123	different grades of ovarian tumor tissues	1108:1148	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	2	56	theme	monoclonal	258:267	arg1	antibodies					269:278	Previously described monoclonal antibodies	237:278	Previously described monoclonal antibodies against cell surface expressed MUC16	237:315	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	12	57	theme	cancer	1791:1796	arg1	treatment					1770:1778	treatment	1770:1778	treatment of ovarian cancer	1770:1796	These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
29708979	4	58	theme	cancers	656:662	arg1	types					647:651	diverse types	639:651	diverse types of cancers	639:662	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	0	59	theme	antibodies	73:82	arg1	characterization					16:31	characterization	16:31	characterization	16:31	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	0	59	theme	antibodies	73:82	arg1	Development					0:10	Development	0:10	Development	0:10	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	4	60	theme	carboxy-terminal	549:564	arg1	CT					567:568	CT	567:568	CT	567:568	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	4	60	theme	carboxy-terminal	549:564	arg1	fragment					571:578	the retained carboxy-terminal (CT) fragment	536:578	the retained carboxy-terminal (CT) fragment of MUC16	536:587	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	11	61	link	O-linked	1610:1617	arg1	glycosylation					1619:1631	O-linked glycosylation	1610:1631	O-linked glycosylation	1610:1631	The CT mAb(s) accurately predict expression of MUC16 since their epitopes are not tandemly repeated and their reactivity may not be dependent on O-linked glycosylation.
29708979	8	62	theme	Immunohistochemical	1076:1094	arg1	analyses					1096:1103	Immunohistochemical analyses	1076:1103	Immunohistochemical analyses on different grades of ovarian tumor tissues	1076:1148	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	2	63	theme	described	248:256	arg1	antibodies					269:278	Previously described monoclonal antibodies	237:278	Previously described monoclonal antibodies against cell surface expressed MUC16	237:315	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	10	64	theme	M11	1381:1383	arg1	mAb					1386:1388	the CA125 (M11) mAb	1370:1388	the CA125 (M11) mAb	1370:1388	For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%).
29708979	0	65	theme	monoclonal	62:71	arg1	antibodies					73:82	carboxy-terminus specific monoclonal antibodies	36:82	carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer	36:139	Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.
29708979	9	66	theme	CA125	1216:1220	arg1	mAb					1228:1230	The CA125 (M11) mAb	1212:1230	The CA125 (M11) mAb	1212:1230	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	10	67	theme	serous	1346:1351	arg1	cases					1363:1367	serous and serous papillary cases	1335:1367	serous and serous papillary cases	1335:1367	For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%).
29708979	8	68	theme	CA125	1187:1191	arg1	reactivity					1173:1182	differential reactivity	1160:1182	differential reactivity of CA125 and MUC16 CT mAbs	1160:1209	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	7	69	theme	OVCAR-3	986:992	arg1	[OVCAR-3					994:1001	OVCAR-3 [OVCAR-3]	986:1002	NIH:OVCAR-3 [OVCAR-3]	982:1002	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	2	70	theme	expressed	301:309	arg1	MUC16					311:315	cell surface expressed MUC16	288:315	cell surface expressed MUC16	288:315	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	2	71	theme	cancer	380:385	arg1	antigen					387:393	cancer antigen 125 (CA125)	380:405	cancer antigen 125 (CA125)	380:405	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	9	72	theme	cases	1324:1328	arg1	33/40					1286:1290	33/40	1286:1290	33/40 (82.5%) of total ovarian cancer cases	1286:1328	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	9	72	theme	cases	1324:1328	arg1	%					1297:1297	82.5%	1293:1297	82.5%	1293:1297	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	9	73	theme	M11	1223:1225	arg1	mAb					1228:1230	The CA125 (M11) mAb	1212:1230	The CA125 (M11) mAb	1212:1230	The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases.
29708979	2	74	theme	surface	293:299	arg1	MUC16					311:315	cell surface expressed MUC16	288:315	cell surface expressed MUC16	288:315	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	7	75	theme	ovarian	960:966	arg1	NIH					982:984	NIH	982:984	NIH:OVCAR-3 [OVCAR-3]	982:1002	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	7	75	theme	ovarian	960:966	arg1	cells					975:979	ovarian cancer cells	960:979	ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3])	960:1003	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	8	76	theme	different	1108:1116	arg1	grades					1118:1123	different grades	1108:1123	different grades of ovarian tumor tissues	1108:1148	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	11	77	theme	O-linked	1610:1617	arg1	glycosylation					1619:1631	O-linked glycosylation	1610:1631	O-linked glycosylation	1610:1631	The CT mAb(s) accurately predict expression of MUC16 since their epitopes are not tandemly repeated and their reactivity may not be dependent on O-linked glycosylation.
29708979	2	78	theme	cell	288:291	arg1	MUC16					311:315	cell surface expressed MUC16	288:315	cell surface expressed MUC16	288:315	Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125).
29708979	7	79	theme	cancer	968:973	arg1	NIH					982:984	NIH	982:984	NIH:OVCAR-3 [OVCAR-3]	982:1002	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	7	79	theme	cancer	968:973	arg1	cells					975:979	ovarian cancer cells	960:979	ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3])	960:1003	For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other.
29708979	3	80	theme	specific	430:437	arg1	location					439:446	a specific location	428:446	a specific location	428:446	MUC16 is cleaved at a specific location, thus, releasing CA125 into the extracellular space.
29708979	8	81	theme	CT	1203:1204	arg1	mAbs					1206:1209	CT mAbs	1203:1209	CT mAbs	1203:1209	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	4	82	theme	diverse	639:645	arg1	types					647:651	diverse types	639:651	diverse types of cancers	639:662	Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers.
29708979	8	83	theme	MUC16	1197:1201	arg1	reactivity					1173:1182	differential reactivity	1160:1182	differential reactivity of CA125 and MUC16 CT mAbs	1160:1209	Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs.
29708979	1	84	theme	ovarian	168:174	arg1	cancer					176:181	ovarian cancer	168:181	ovarian cancer	168:181	MUC16 is overexpressed in ovarian cancer and plays important roles in invasion and metastasis.
28067406	6	0	theme	homomer	995:1001	arg1	assembly					1003:1010	Ninj1 homomer assembly	989:1010	Ninj1 homomer assembly	989:1010	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	8	1	theme	Fluorescence-activated	1120:1141	arg1	transfer					1187:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer	1120:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	9	2	theme	N-glycosylation	1562:1576	arg1	motif					1578:1582	an N-glycosylation motif	1559:1582	an N-glycosylation motif	1559:1582	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	9	3	theme	cis-interacting	1588:1602	arg1	region					1618:1623	cis-interacting intracellular region	1588:1623	cis-interacting intracellular region	1588:1623	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	6	4	theme	Ninj1	989:993	arg1	assembly					1003:1010	Ninj1 homomer assembly	989:1010	Ninj1 homomer assembly	989:1010	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	2	5	theme	Ninj1	308:312	arg1	modification					314:325	Ninj1 modification	308:325	Ninj1 modification	308:325	Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction.
28067406	8	6	theme	Ninj1	1270:1274	arg1	cis-interaction					1276:1290	the Ninj1 cis-interaction	1266:1290	the Ninj1 cis-interaction	1266:1290	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	8	7	theme	sorting-based	1148:1160	arg1	transfer					1187:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer	1120:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	3	8	from	Asn60	503:507	arg1	N-glycosylation					484:498	N-glycosylation	484:498	N-glycosylation at Asn60	484:507	We showed that Ninj1 assembles into a homomeric complex via a cis-interaction mediated by the intracellular region and N-glycosylation at Asn60 .
28067406	3	8	from	Asn60	503:507	arg1	region					473:478	the intracellular region	455:478	the intracellular region	455:478	We showed that Ninj1 assembles into a homomeric complex via a cis-interaction mediated by the intracellular region and N-glycosylation at Asn60 .
28067406	4	9	theme	cell	688:691	arg1	sorter					693:698	fluorescence-activated cell sorter	665:698	fluorescence-activated cell sorter	665:698	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	4	10	theme	Förster	599:605	arg1	transfer					624:631	Förster resonance energy transfer	599:631	Förster resonance energy transfer using a confocal microscope	599:659	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	8	11	theme	energy	1180:1185	arg1	transfer					1187:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer	1120:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	8	12	theme	cell	1143:1146	arg1	transfer					1187:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer	1120:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	6	13	theme	Co-immunoprecipitation	839:860	arg1	assays					862:867	Co-immunoprecipitation assays	839:867	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1	839:903	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	5	14	theme	monomeric	774:782	arg1	molecules					790:798	two to six monomeric Ninj1 molecules	763:798	two to six monomeric Ninj1 molecules	763:798	We further observed the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules by a formaldehyde cross-linking assay.
28067406	10	15	theme	homomer	1810:1816	arg1	assembly					1818:1825	Ninj1 homomer assembly	1804:1825	Ninj1 homomer assembly	1804:1825	Taken together, these data show that Ninj1 assembles into a homomeric protein complex and that N-glycosylation is a prerequisite for Ninj1 homomer assembly.
28067406	8	16	theme	cross-linking	1312:1324	arg1	assay					1326:1330	a formaldehyde cross-linking assay	1297:1330	a formaldehyde cross-linking assay	1297:1330	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	8	17	theme	resonance	1170:1178	arg1	transfer					1187:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer	1120:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	2	18	from	modification	314:325	arg1	cis-interaction					348:362	the cis-interaction	344:362	the cis-interaction	344:362	Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction.
28067406	8	19	theme	homomeric	1415:1423	arg1	formation					1433:1441	Ninj1 homomeric complex formation	1409:1441	Ninj1 homomeric complex formation	1409:1441	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	1	20	theme	homophilic	146:155	arg1	molecule					166:173	a homophilic adhesion molecule	144:173	a homophilic adhesion molecule	144:173	Ninjurin1 (Ninj1) is a cell surface protein known as a homophilic adhesion molecule.
28067406	8	21	theme	formaldehyde	1299:1310	arg1	cross-linking					1312:1324	formaldehyde cross-linking	1299:1324	a formaldehyde cross-linking assay	1297:1330	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	6	22	theme	Leu101	958:963	arg1	-Ala110					965:971	Leu101 -Ala110	958:971	Leu101 -Ala110	958:971	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	8	23	theme	Förster	1162:1168	arg1	transfer					1187:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer	1120:1194	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	13	24	dep	2219-2230	1851:1859	arg1	118					1846:1848	118	1846:1848	118	1846:1848	118: 2219-2230, 2017.
28067406	2	25	theme	endothelial	258:268	arg1	cells					270:274	endothelial cells	258:274	endothelial cells	258:274	Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction.
28067406	1	26	theme	adhesion	157:164	arg1	molecule					166:173	a homophilic adhesion molecule	144:173	a homophilic adhesion molecule	144:173	Ninjurin1 (Ninj1) is a cell surface protein known as a homophilic adhesion molecule.
28067406	9	27	theme	intracellular	1604:1616	arg1	region					1618:1623	cis-interacting intracellular region	1588:1623	cis-interacting intracellular region	1588:1623	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	9	28	theme	In	1444:1445	arg1	analysis					1454:1461	In silico analysis	1444:1461	In silico analysis	1444:1461	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	8	29	theme	transfer	1187:1194	arg1	assays					1196:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays	1120:1201	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	2	30	from	structure	331:339	arg1	cis-interaction					348:362	the cis-interaction	344:362	the cis-interaction	344:362	Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction.
28067406	3	31	gly	N-glycosylation	484:498	arg1	Asn60					503:507	Asn60	503:507	Asn60	503:507	We showed that Ninj1 assembles into a homomeric complex via a cis-interaction mediated by the intracellular region and N-glycosylation at Asn60 .
28067406	3	31	gly	N-glycosylation	484:498	arg2	Asn60					503:507	Asn60	503:507	Asn60	503:507	We showed that Ninj1 assembles into a homomeric complex via a cis-interaction mediated by the intracellular region and N-glycosylation at Asn60 .
28067406	9	32	contain	contains	1550:1557	arg2	region					1618:1623	cis-interacting intracellular region	1588:1623	cis-interacting intracellular region	1588:1623	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	9	32	contain	contains	1550:1557	arg1	sequence					1541:1548	the conserved sequence	1527:1548	the conserved sequence	1527:1548	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	9	32	contain	contains	1550:1557	arg2	motif					1578:1582	an N-glycosylation motif	1559:1582	an N-glycosylation motif	1559:1582	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	3	33	theme	homomeric	403:411	arg1	complex					413:419	a homomeric complex	401:419	a homomeric complex	401:419	We showed that Ninj1 assembles into a homomeric complex via a cis-interaction mediated by the intracellular region and N-glycosylation at Asn60 .
28067406	10	34	theme	Ninj1	1804:1808	arg1	assembly					1818:1825	Ninj1 homomer assembly	1804:1825	Ninj1 homomer assembly	1804:1825	Taken together, these data show that Ninj1 assembles into a homomeric protein complex and that N-glycosylation is a prerequisite for Ninj1 homomer assembly.
28067406	6	35	theme	epitope-tagged	874:887	arg1	Ninj1					899:903	epitope-tagged truncated Ninj1	874:903	epitope-tagged truncated Ninj1	874:903	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	8	36	theme	Ninj1	1409:1413	arg1	formation					1433:1441	Ninj1 homomeric complex formation	1409:1441	Ninj1 homomeric complex formation	1409:1441	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	5	37	theme	Ninj1	725:729	arg1	complexes					741:749	the Ninj1 homomeric complexes	721:749	the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules	721:798	We further observed the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules by a formaldehyde cross-linking assay.
28067406	7	38	theme	Ninj1	1013:1017	arg1	N-glycosylation					1019:1033	Ninj1 N-glycosylation	1013:1033	Ninj1 N-glycosylation	1013:1033	Ninj1 N-glycosylation was characterized by treatment of tunicamycin and substitution of Asn to Gln or Ala.
28067406	8	39	theme	N-glycosylation	1363:1377	arg1	interruption					1347:1358	interruption	1347:1358	interruption of N-glycosylation by Asn substitution	1347:1397	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	9	40	gly	N-glycosylation	1562:1576	arg2	motif					1578:1582	an N-glycosylation motif	1559:1582	an N-glycosylation motif	1559:1582	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	4	41	theme	confocal	641:648	arg1	microscope					650:659	a confocal microscope	639:659	a confocal microscope	639:659	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	6	42	with	assays	862:867	arg1	Ninj1					899:903	epitope-tagged truncated Ninj1	874:903	epitope-tagged truncated Ninj1	874:903	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	5	43	theme	homomeric	731:739	arg1	complexes					741:749	the Ninj1 homomeric complexes	721:749	the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules	721:798	We further observed the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules by a formaldehyde cross-linking assay.
28067406	8	44	theme	complex	1425:1431	arg1	formation					1433:1441	Ninj1 homomeric complex formation	1409:1441	Ninj1 homomeric complex formation	1409:1441	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	0	45	theme	Protein	37:43	arg1	Complex					45:51	a Homomeric Protein Complex	25:51	a Homomeric Protein Complex Maintained by N-linked Glycosylation	25:88	Ninjurin1 Assembles Into a Homomeric Protein Complex Maintained by N-linked Glycosylation.
28067406	6	46	theme	intracellular	924:936	arg1	region					938:943	the intracellular region	920:943	the intracellular region encompassing Leu101 -Ala110	920:971	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	2	47	theme	Ninj1	227:231	arg1	trans-interaction					206:222	a trans-interaction	204:222	a trans-interaction of Ninj1 between immune cells and endothelial cells	204:274	Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction.
28067406	9	48	theme	Ninj1	1647:1651	arg1	assembly					1661:1668	Ninj1 homomer assembly	1647:1668	Ninj1 homomer assembly	1647:1668	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	0	49	theme	Homomeric	27:35	arg1	Complex					45:51	a Homomeric Protein Complex	25:51	a Homomeric Protein Complex Maintained by N-linked Glycosylation	25:88	Ninjurin1 Assembles Into a Homomeric Protein Complex Maintained by N-linked Glycosylation.
28067406	4	50	theme	YFP-tagged	579:588	arg1	Ninj1					590:594	YFP-tagged Ninj1	579:594	YFP-tagged Ninj1	579:594	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	14	51	dep	©	1868:1868	arg1	Inc.					1894:1897	Inc.	1894:1897	Inc.	1894:1897	© 2017 Wiley Periodicals, Inc.
28067406	10	52	theme	protein	1741:1747	arg1	complex					1749:1755	a homomeric protein complex	1729:1755	a homomeric protein complex	1729:1755	Taken together, these data show that Ninj1 assembles into a homomeric protein complex and that N-glycosylation is a prerequisite for Ninj1 homomer assembly.
28067406	5	53	theme	cross-linking	818:830	arg1	assay					832:836	a formaldehyde cross-linking assay	803:836	a formaldehyde cross-linking assay	803:836	We further observed the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules by a formaldehyde cross-linking assay.
28067406	9	54	theme	conserved	1531:1539	arg1	sequence					1541:1548	the conserved sequence	1527:1548	the conserved sequence	1527:1548	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	10	55	theme	homomeric	1731:1739	arg1	complex					1749:1755	a homomeric protein complex	1729:1755	a homomeric protein complex	1729:1755	Taken together, these data show that Ninj1 assembles into a homomeric protein complex and that N-glycosylation is a prerequisite for Ninj1 homomer assembly.
28067406	7	56	theme	Asn	1101:1103	arg1	substitution					1085:1096	substitution	1085:1096	substitution of Asn to Gln or Ala.	1085:1118	Ninj1 N-glycosylation was characterized by treatment of tunicamycin and substitution of Asn to Gln or Ala.
28067406	7	56	theme	Asn	1101:1103	arg1	tunicamycin					1069:1079	tunicamycin	1069:1079	tunicamycin	1069:1079	Ninj1 N-glycosylation was characterized by treatment of tunicamycin and substitution of Asn to Gln or Ala.
28067406	4	57	theme	resonance	607:615	arg1	transfer					624:631	Förster resonance energy transfer	599:631	Förster resonance energy transfer using a confocal microscope	599:659	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	4	58	theme	Ninj1	549:553	arg1	proteins					555:562	Ninj1 proteins	549:562	Ninj1 proteins	549:562	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	5	59	dep	six	770:772	arg1	to					767:768	to	767:768	to	767:768	We further observed the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules by a formaldehyde cross-linking assay.
28067406	0	60	link	N-linked	67:74	arg1	Glycosylation					76:88	N-linked Glycosylation	67:88	N-linked Glycosylation	67:88	Ninjurin1 Assembles Into a Homomeric Protein Complex Maintained by N-linked Glycosylation.
28067406	9	61	dep	In	1444:1445	arg1	silico					1447:1452	silico	1447:1452	silico	1447:1452	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	1	62	theme	cell	114:117	arg1	Ninjurin1					91:99	Ninjurin1	91:99	Ninjurin1 (Ninj1)	91:107	Ninjurin1 (Ninj1) is a cell surface protein known as a homophilic adhesion molecule.
28067406	1	62	theme	cell	114:117	arg1	protein					127:133	a cell surface protein	112:133	a cell surface protein known as a homophilic adhesion molecule	112:173	Ninjurin1 (Ninj1) is a cell surface protein known as a homophilic adhesion molecule.
28067406	4	63	theme	energy	617:622	arg1	transfer					624:631	Förster resonance energy transfer	599:631	Förster resonance energy transfer using a confocal microscope	599:659	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	6	64	theme	truncated	889:897	arg1	Ninj1					899:903	epitope-tagged truncated Ninj1	874:903	epitope-tagged truncated Ninj1	874:903	Co-immunoprecipitation assays with epitope-tagged truncated Ninj1 suggested that the intracellular region encompassing Leu101 -Ala110 participates in Ninj1 homomer assembly.
28067406	7	65	theme	substitution	1085:1096	arg1	treatment					1056:1064	treatment	1056:1064	treatment of tunicamycin and substitution of Asn to Gln or Ala.	1056:1118	Ninj1 N-glycosylation was characterized by treatment of tunicamycin and substitution of Asn to Gln or Ala.
28067406	1	66	theme	surface	119:125	arg1	Ninjurin1					91:99	Ninjurin1	91:99	Ninjurin1 (Ninj1)	91:107	Ninjurin1 (Ninj1) is a cell surface protein known as a homophilic adhesion molecule.
28067406	1	66	theme	surface	119:125	arg1	protein					127:133	a cell surface protein	112:133	a cell surface protein known as a homophilic adhesion molecule	112:173	Ninjurin1 (Ninj1) is a cell surface protein known as a homophilic adhesion molecule.
28067406	8	67	theme	Asn	1382:1384	arg1	substitution					1386:1397	Asn substitution	1382:1397	Asn substitution	1382:1397	Fluorescence-activated cell sorting-based Förster resonance energy transfer assays further demonstrated that N-glycosylation is indispensable for the Ninj1 cis-interaction, and a formaldehyde cross-linking assay confirmed that interruption of N-glycosylation by Asn substitution disrupted Ninj1 homomeric complex formation.
28067406	3	68	theme	intracellular	459:471	arg1	region					473:478	the intracellular region	455:478	the intracellular region	455:478	We showed that Ninj1 assembles into a homomeric complex via a cis-interaction mediated by the intracellular region and N-glycosylation at Asn60 .
28067406	0	69	theme	N-linked	67:74	arg1	Glycosylation					76:88	N-linked Glycosylation	67:88	N-linked Glycosylation	67:88	Ninjurin1 Assembles Into a Homomeric Protein Complex Maintained by N-linked Glycosylation.
28067406	2	70	theme	Previous	176:183	arg1	studies					185:191	Previous studies	176:191	Previous studies	176:191	Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction.
28067406	2	71	theme	immune	241:246	arg1	cells					248:252	immune cells	241:252	immune cells	241:252	Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction.
28067406	9	72	theme	homomer	1653:1659	arg1	assembly					1661:1668	Ninj1 homomer assembly	1647:1668	Ninj1 homomer assembly	1647:1668	In silico analysis revealed that Ninj1 is highly conserved in vertebrates and that the conserved sequence contains an N-glycosylation motif and cis-interacting intracellular region, which participate in Ninj1 homomer assembly.
28067406	4	73	theme	fluorescence-activated	665:686	arg1	sorter					693:698	fluorescence-activated cell sorter	665:698	fluorescence-activated cell sorter	665:698	We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter.
28067406	5	74	theme	Ninj1	784:788	arg1	molecules					790:798	two to six monomeric Ninj1 molecules	763:798	two to six monomeric Ninj1 molecules	763:798	We further observed the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules by a formaldehyde cross-linking assay.
28067406	5	75	theme	formaldehyde	805:816	arg1	assay					832:836	a formaldehyde cross-linking assay	803:836	a formaldehyde cross-linking assay	803:836	We further observed the Ninj1 homomeric complexes composed of two to six monomeric Ninj1 molecules by a formaldehyde cross-linking assay.
28067406	7	76	theme	tunicamycin	1069:1079	arg1	treatment					1056:1064	treatment	1056:1064	treatment of tunicamycin and substitution of Asn to Gln or Ala.	1056:1118	Ninj1 N-glycosylation was characterized by treatment of tunicamycin and substitution of Asn to Gln or Ala.
31733946	9	0	theme	different	1713:1721	arg1	locations					1723:1731	different locations	1713:1731	different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1713:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	8	1	theme	HAI	1463:1465	arg1	activity					1467:1474	HAI activity	1463:1474	HAI activity in the elicited sera against A/Hubei/01/2010	1463:1519	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31733946	1	2	theme	pathogenic	256:265	arg1	viruses					283:289	low pathogenic avian influenza viruses	252:289	low pathogenic avian influenza viruses	252:289	Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry.
31733946	7	3	theme	2.3.2.1	1334:1340	arg1	A/Hubei/01/2010					1364:1378	A/Hubei/01/2010	1364:1378	A/Hubei/01/2010	1364:1378	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	7	3	theme	2.3.2.1	1334:1340	arg1	viruses					1347:1353	clade 2.3.2.1 H5Nx viruses	1328:1353	clade 2.3.2.1 H5Nx viruses	1328:1353	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	7	4	theme	elicited	1282:1289	arg1	antibodies					1291:1300	the elicited antibodies	1278:1300	the elicited antibodies	1278:1300	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	0	5	contain	contains	22:29	arg2	epitopes					41:48	two major epitopes	31:48	two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses	31:154	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	0	5	contain	contains	22:29	arg1	vaccine					14:20	Human COBRA 2 vaccine	0:20	Human COBRA 2 vaccine	0:20	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	3	6	theme	HA	545:546	arg1	COBRA					596:600	Human-Avian COBRA 2	584:602	Human-Avian COBRA 2 (Hu-Av CO)	584:613	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	6	theme	HA	545:546	arg1	antigens					548:555	these HA antigens	539:555	these HA antigens	539:555	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	6	theme	HA	545:546	arg1	COBRA					564:568	Human COBRA 2	558:570	Human COBRA 2 (Hu-CO)	558:578	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	1	7	theme	influenza	273:281	arg1	viruses					283:289	low pathogenic avian influenza viruses	252:289	low pathogenic avian influenza viruses	252:289	Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry.
31733946	9	8	from	driver	1652:1657	arg1	elicitation					1666:1676	the elicitation	1662:1676	the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1662:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	9	theme	H5	1746:1747	arg1	molecules					1752:1760	wild-type H5 HA molecules	1736:1760	wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1736:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	10	with	antibodies	1681:1690	arg1	activity					1701:1708	HAI activity	1697:1708	HAI activity	1697:1708	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	6	11	from	responses	1137:1145	arg1	mice					1150:1153	mice	1150:1153	mice	1150:1153	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	5	12	from	similar	941:947	arg1	region					970:975	the globular head region	952:975	the globular head region	952:975	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	1	13	theme	influenza	180:188	arg1	viruses					190:196	Highly pathogenic H5N1 influenza viruses	157:196	Highly pathogenic H5N1 influenza viruses	157:196	Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry.
31733946	7	14	theme	HAI	1307:1309	arg1	activity					1311:1318	HAI activity	1307:1318	HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010	1307:1378	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	7	15	theme	CO	1271:1272	arg1	HA					1274:1275	the Hu-Av CO HA	1261:1275	the Hu-Av CO HA	1261:1275	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	0	16	theme	viruses	148:154	arg1	clades					138:143	heterologous clades	125:143	heterologous clades of viruses	125:154	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	6	17	theme	immune	1130:1135	arg1	responses					1137:1145	immune responses	1130:1145	immune responses in mice	1130:1153	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	4	18	theme	various	874:880	arg1	viruses					897:903	various H5Nx influenza viruses	874:903	various H5Nx influenza viruses	874:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	5	19	theme	amino	1003:1007	arg1	acids					1009:1013	amino acids 140, 141, 155, and 156	1003:1036	amino acids 140, 141, 155, and 156	1003:1036	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	9	20	gly	glycosylation	1588:1600	arg1	location					1610:1617	this location	1605:1617	this location in the Hu-CO HA antigen	1605:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	20	gly	glycosylation	1588:1600	arg2	location					1610:1617	this location	1605:1617	this location in the Hu-CO HA antigen	1605:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	4	21	theme	influenza	887:895	arg1	viruses					897:903	various H5Nx influenza viruses	874:903	various H5Nx influenza viruses	874:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	3	22	theme	same	737:740	arg1	viruses					742:748	the same viruses	733:748	the same viruses	733:748	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	7	23	located	found	1252:1256	arg2	residues					1243:1250	the Ser-Ala residues	1231:1250	the Ser-Ala residues found in the Hu-Av CO HA	1231:1275	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	7	23	located	found	1252:1256	arg1	HA					1274:1275	the Hu-Av CO HA	1261:1275	the Hu-Av CO HA	1261:1275	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	9	24	theme	key	1648:1650	arg1	driver					1652:1657	a key driver	1646:1657	a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1646:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	24	theme	key	1648:1650	arg1	glycosylation					1588:1600	a putative N-linked glycosylation	1568:1600	a putative N-linked glycosylation at this location in the Hu-CO HA antigen	1568:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	4	25	theme	fordifferential	837:851	arg1	residues					784:791	residues	784:791	residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses	784:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	4	25	theme	fordifferential	837:851	arg1	activity					857:864	critical fordifferential HAI activity	828:864	critical fordifferential HAI activity against various H5Nx influenza viruses	828:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	7	26	theme	Ser-Ala	1235:1241	arg1	residues					1243:1250	the Ser-Ala residues	1231:1250	the Ser-Ala residues found in the Hu-Av CO HA	1231:1275	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	9	27	theme	viral	1806:1810	arg1	infection					1812:1820	viral infection	1806:1820	viral infection	1806:1820	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	8	28	from	activity	1467:1474	arg1	sera					1492:1495	the elicited sera	1479:1495	the elicited sera	1479:1495	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31733946	9	29	theme	N-linked	1579:1586	arg1	driver					1652:1657	a key driver	1646:1657	a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1646:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	29	theme	N-linked	1579:1586	arg1	glycosylation					1588:1600	a putative N-linked glycosylation	1568:1600	a putative N-linked glycosylation at this location in the Hu-CO HA antigen	1568:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	30	from	locations	1723:1731	arg1	molecules					1752:1760	wild-type H5 HA molecules	1736:1760	wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1736:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	6	31	theme	chimeric	1089:1096	arg1	proteins					1101:1108	chimeric HA proteins	1089:1108	chimeric HA proteins	1089:1108	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	3	32	theme	Human-Avian	584:594	arg1	CO					611:612	Hu-Av CO	605:612	Hu-Av CO	605:612	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	32	theme	Human-Avian	584:594	arg1	COBRA					596:600	Human-Avian COBRA 2	584:602	Human-Avian COBRA 2 (Hu-Av CO)	584:613	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	32	theme	Human-Avian	584:594	arg1	antigens					548:555	these HA antigens	539:555	these HA antigens	539:555	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	1	33	theme	pathogenic	164:173	arg1	viruses					190:196	Highly pathogenic H5N1 influenza viruses	157:196	Highly pathogenic H5N1 influenza viruses	157:196	Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry.
31733946	9	34	theme	influenza	1856:1864	arg1	virus					1866:1870	H5 influenza virus	1853:1870	H5 influenza virus induced disease	1853:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	35	theme	HA	1632:1633	arg1	antigen					1635:1641	the Hu-CO HA antigen	1622:1641	the Hu-CO HA antigen	1622:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	3	36	from	clades	710:715	arg1	viruses					689:695	viruses	689:695	viruses from various clades	689:715	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	9	37	theme	induced	1872:1878	arg1	disease					1880:1886	H5 influenza virus induced disease	1853:1886	H5 influenza virus induced disease	1853:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	0	38	theme	antibody	98:105	arg1	responses					107:115	neutralizing antibody responses	85:115	neutralizing antibody responses against heterologous clades of viruses	85:154	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	0	39	theme	Human	0:4	arg1	vaccine					14:20	Human COBRA 2 vaccine	0:20	Human COBRA 2 vaccine	0:20	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	2	40	theme	based	429:433	arg1	vaccines					435:442	two hemagglutinin (HA) based vaccines	406:442	two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA)	406:528	Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA).
31733946	7	41	from	pair	1173:1176	arg1	HA					1211:1212	the Hu-CO HA	1201:1212	the Hu-CO HA	1201:1212	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	3	42	theme	Hu-Av	605:609	arg1	CO					611:612	Hu-Av CO	605:612	Hu-Av CO	605:612	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	42	theme	Hu-Av	605:609	arg1	COBRA					596:600	Human-Avian COBRA 2	584:602	Human-Avian COBRA 2 (Hu-Av CO)	584:613	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	0	43	theme	major	35:39	arg1	epitopes					41:48	two major epitopes	31:48	two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses	31:154	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	9	44	from	location	1610:1617	arg1	antigen					1635:1641	the Hu-CO HA antigen	1622:1641	the Hu-CO HA antigen	1622:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	44	from	location	1610:1617	arg1	driver					1652:1657	a key driver	1646:1657	a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1646:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	44	from	location	1610:1617	arg1	glycosylation					1588:1600	a putative N-linked glycosylation	1568:1600	a putative N-linked glycosylation at this location in the Hu-CO HA antigen	1568:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	7	45	from	position	1181:1188	arg1	pair					1173:1176	the Asn-Thr pair	1161:1176	the Asn-Thr pair at position 155-156 in the Hu-CO HA	1161:1212	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	7	46	theme	Asn-Thr	1165:1171	arg1	pair					1173:1176	the Asn-Thr pair	1161:1176	the Asn-Thr pair at position 155-156 in the Hu-CO HA	1161:1212	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	9	47	theme	antibodies	1681:1690	arg1	elicitation					1666:1676	the elicitation	1662:1676	the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1662:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	3	48	theme	hemagglutination-inhibition	638:664	arg1	activity					672:679	hemagglutination-inhibition (HAI) activity	638:679	hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses	638:748	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	9	49	theme	putative	1570:1577	arg1	driver					1652:1657	a key driver	1646:1657	a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1646:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	49	theme	putative	1570:1577	arg1	glycosylation					1588:1600	a putative N-linked glycosylation	1568:1600	a putative N-linked glycosylation at this location in the Hu-CO HA antigen	1568:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	50	theme	HAI	1697:1699	arg1	activity					1701:1708	HAI activity	1697:1708	HAI activity	1697:1708	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	8	51	theme	Hu-Av	1441:1445	arg1	molecule					1453:1460	the Hu-Av CO HA molecule	1437:1460	the Hu-Av CO HA molecule	1437:1460	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31733946	7	52	theme	H5Nx	1342:1345	arg1	A/Hubei/01/2010					1364:1378	A/Hubei/01/2010	1364:1378	A/Hubei/01/2010	1364:1378	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	7	52	theme	H5Nx	1342:1345	arg1	viruses					1347:1353	clade 2.3.2.1 H5Nx viruses	1328:1353	clade 2.3.2.1 H5Nx viruses	1328:1353	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	5	53	theme	globular	956:963	arg1	region					970:975	the globular head region	952:975	the globular head region	952:975	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	8	54	theme	HA	1450:1451	arg1	molecule					1453:1460	the Hu-Av CO HA molecule	1437:1460	the Hu-Av CO HA molecule	1437:1460	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31733946	6	55	used	used	1115:1118	arg2	proteins					1101:1108	chimeric HA proteins	1089:1108	chimeric HA proteins	1089:1108	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	1	56	theme	low	252:254	arg1	viruses					283:289	low pathogenic avian influenza viruses	252:289	low pathogenic avian influenza viruses	252:289	Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry.
31733946	7	57	theme	clade	1328:1332	arg1	A/Hubei/01/2010					1364:1378	A/Hubei/01/2010	1364:1378	A/Hubei/01/2010	1364:1378	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	7	57	theme	clade	1328:1332	arg1	viruses					1347:1353	clade 2.3.2.1 H5Nx viruses	1328:1353	clade 2.3.2.1 H5Nx viruses	1328:1353	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	4	58	theme	HA	806:807	arg1	molecules					809:817	these two HA molecules	796:817	these two HA molecules	796:817	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	3	59	theme	HAI	667:669	arg1	activity					672:679	hemagglutination-inhibition (HAI) activity	638:679	hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses	638:748	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	1	60	theme	avian	267:271	arg1	viruses					283:289	low pathogenic avian influenza viruses	252:289	low pathogenic avian influenza viruses	252:289	Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry.
31733946	6	61	theme	HA	1077:1078	arg1	antigen					1080:1086	each HA antigen	1072:1086	each HA antigen	1072:1086	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	9	62	theme	wild-type	1736:1744	arg1	molecules					1752:1760	wild-type H5 HA molecules	1736:1760	wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1736:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	3	63	theme	various	702:708	arg1	clades					710:715	various clades	702:715	various clades	702:715	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	64	with	antibodies	622:631	arg1	activity					672:679	hemagglutination-inhibition (HAI) activity	638:679	hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses	638:748	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	1	65	theme	H5N1	175:178	arg1	viruses					190:196	Highly pathogenic H5N1 influenza viruses	157:196	Highly pathogenic H5N1 influenza viruses	157:196	Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry.
31733946	9	66	theme	HA	1749:1750	arg1	molecules					1752:1760	wild-type H5 HA molecules	1736:1760	wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1736:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	8	67	from	positions	1424:1432	arg1	molecule					1453:1460	the Hu-Av CO HA molecule	1437:1460	the Hu-Av CO HA molecule	1437:1460	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31733946	3	68	theme	Human	558:562	arg1	Hu-CO					573:577	Hu-CO	573:577	Hu-CO	573:577	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	68	theme	Human	558:562	arg1	antigens					548:555	these HA antigens	539:555	these HA antigens	539:555	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	3	68	theme	Human	558:562	arg1	COBRA					564:568	Human COBRA 2	558:570	Human COBRA 2 (Hu-CO)	558:578	Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses.
31733946	6	69	theme	amino	1057:1061	arg1	acids					1063:1067	these amino acids	1051:1067	these amino acids in each HA antigen	1051:1086	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	0	70	theme	heterologous	125:136	arg1	clades					138:143	heterologous clades	125:143	heterologous clades of viruses	125:154	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	7	71	theme	Hu-Av	1265:1269	arg1	HA					1274:1275	the Hu-Av CO HA	1261:1275	the Hu-Av CO HA	1261:1275	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	9	72	theme	differential	1775:1786	arg1	neutralization					1788:1801	differential neutralization	1775:1801	differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1775:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	5	73	from	region	970:975	arg1	antigens					917:924	The two HA antigens	906:924	The two HA antigens	906:924	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	5	73	from	region	970:975	arg1	similar					941:947	similar	941:947	similar	941:947	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	4	74	theme	H5Nx	882:885	arg1	viruses					897:903	various H5Nx influenza viruses	874:903	various H5Nx influenza viruses	874:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	4	75	theme	critical	828:835	arg1	residues					784:791	residues	784:791	residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses	784:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	4	75	theme	critical	828:835	arg1	activity					857:864	critical fordifferential HAI activity	828:864	critical fordifferential HAI activity against various H5Nx influenza viruses	828:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	9	76	theme	infection	1812:1820	arg1	neutralization					1788:1801	differential neutralization	1775:1801	differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1775:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	4	77	theme	HAI	853:855	arg1	residues					784:791	residues	784:791	residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses	784:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	4	77	theme	HAI	853:855	arg1	activity					857:864	critical fordifferential HAI activity	828:864	critical fordifferential HAI activity against various H5Nx influenza viruses	828:903	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	6	78	theme	HA	1098:1099	arg1	proteins					1101:1108	chimeric HA proteins	1089:1108	chimeric HA proteins	1089:1108	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	9	79	theme	protection	1826:1835	arg1	neutralization					1788:1801	differential neutralization	1775:1801	differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1775:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	2	80	theme	reactive	505:512	arg1	COBRA					523:527	COBRA	523:527	COBRA	523:527	Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA).
31733946	2	80	theme	reactive	505:512	arg1	antigen					514:520	computationally optimized broadly reactive antigen	471:520	computationally optimized broadly reactive antigen (COBRA)	471:528	Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA).
31733946	2	81	theme	optimized	487:495	arg1	COBRA					523:527	COBRA	523:527	COBRA	523:527	Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA).
31733946	2	81	theme	optimized	487:495	arg1	antigen					514:520	computationally optimized broadly reactive antigen	471:520	computationally optimized broadly reactive antigen (COBRA)	471:528	Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA).
31733946	9	82	theme	H5	1853:1854	arg1	virus					1866:1870	H5 influenza virus	1853:1870	H5 influenza virus induced disease	1853:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	0	83	theme	neutralizing	85:96	arg1	responses					107:115	neutralizing antibody responses	85:115	neutralizing antibody responses against heterologous clades of viruses	85:154	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	5	84	theme	HA	914:915	arg1	antigens					917:924	The two HA antigens	906:924	The two HA antigens	906:924	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	5	84	theme	HA	914:915	arg1	similar					941:947	similar	941:947	similar	941:947	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	9	85	theme	Hu-CO	1626:1630	arg1	antigen					1635:1641	the Hu-CO HA antigen	1622:1641	the Hu-CO HA antigen	1622:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	86	theme	virus	1866:1870	arg1	disease					1880:1886	H5 influenza virus induced disease	1853:1886	H5 influenza virus induced disease	1853:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	2	87	dep	based	429:433	arg1	hemagglutinin					410:422	hemagglutinin	410:422	hemagglutinin (HA)	410:427	Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA).
31733946	2	87	dep	based	429:433	arg1	HA					425:426	HA	425:426	HA	425:426	Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA).
31733946	7	88	theme	Hu-CO	1205:1209	arg1	HA					1211:1212	the Hu-CO HA	1201:1212	the Hu-CO HA	1201:1212	When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010.
31733946	8	89	theme	Asn-Thr	1391:1397	arg1	motif					1399:1403	this Asn-Thr motif	1386:1403	this Asn-Thr motif	1386:1403	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31733946	0	90	theme	COBRA	6:10	arg1	vaccine					14:20	Human COBRA 2 vaccine	0:20	Human COBRA 2 vaccine	0:20	Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.
31733946	4	91	from	residues	784:791	arg1	molecules					809:817	these two HA molecules	796:817	these two HA molecules	796:817	Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses.
31733946	6	92	from	acids	1063:1067	arg1	antigen					1080:1086	each HA antigen	1072:1086	each HA antigen	1072:1086	By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice.
31733946	5	93	theme	head	965:968	arg1	region					970:975	the globular head region	952:975	the globular head region	952:975	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	5	94	from	acids	1009:1013	arg1	residues					991:998	4 residues	989:998	4 residues at amino acids 140, 141, 155, and 156	989:1036	The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156.
31733946	9	95	link	N-linked	1579:1586	arg1	driver					1652:1657	a key driver	1646:1657	a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease	1646:1886	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	9	95	link	N-linked	1579:1586	arg1	glycosylation					1588:1600	a putative N-linked glycosylation	1568:1600	a putative N-linked glycosylation at this location in the Hu-CO HA antigen	1568:1641	We speculate that a putative N-linked glycosylation at this location in the Hu-CO HA antigen is a key driver in the elicitation of antibodies with HAI activity to different locations on wild-type H5 HA molecules resulting in differential neutralization of viral infection and protection in vivo against H5 influenza virus induced disease.
31733946	8	96	theme	elicited	1483:1490	arg1	sera					1492:1495	the elicited sera	1479:1495	the elicited sera	1479:1495	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31733946	8	97	theme	CO	1447:1448	arg1	molecule					1453:1460	the Hu-Av CO HA molecule	1437:1460	the Hu-Av CO HA molecule	1437:1460	When this Asn-Thr motif was added at these positions in the Hu-Av CO HA molecule, HAI activity in the elicited sera against A/Hubei/01/2010 was significantly increased.
31015322	8	0	theme	general	1168:1174	arg1	system.IMPORTANCE					1190:1206	a bacterial general glycosylation system.IMPORTANCE	1156:1206	a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry	1156:1249	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	14	1	from	bacteria	2248:2255	arg1	emergence					2201:2209	the emergence	2197:2209	the emergence of posttranslational modification in bacteria	2197:2255	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	11	2	theme	proteomic	1681:1689	arg1	strategy					1691:1698	a quantitative proteomic strategy	1666:1698	a quantitative proteomic strategy to monitor alterations in the C. jejuni proteome	1666:1747	To achieve this, we employed a quantitative proteomic strategy to monitor alterations in the C. jejuni proteome.
31015322	2	3	theme	glycosylation	323:335	arg1	systems					337:343	general protein glycosylation systems	307:343	general protein glycosylation systems	307:343	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	2	4	from	roles	298:302	arg1	bacteria					348:355	bacteria	348:355	bacteria using the enteropathogen Campylobacter jejuni as a well-defined example	348:427	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	3	5	from	changes	498:504	arg1	proteome					523:530	the C. jejuni proteome	509:530	the C. jejuni proteome	509:530	By using a quantitative proteomic strategy, we were able to monitor changes in the C. jejuni proteome when glycosylation is disrupted.
31015322	8	6	theme	glycosylation	1282:1294	arg1	systems					1296:1302	glycosylation systems	1282:1302	glycosylation systems in bacteria	1282:1314	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	13	7	theme	novel	1888:1892	arg1	roles					1894:1898	novel roles	1888:1898	novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction	1888:2042	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	10	8	theme	poisoning	1467:1475	arg1	bacterium					1477:1485	a major food poisoning bacterium	1454:1485	a major food poisoning bacterium	1454:1485	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	8	theme	poisoning	1467:1475	arg1	jejuni					1502:1507	Campylobacter jejuni	1488:1507	Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification	1488:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	3	9	theme	C.	513:514	arg1	proteome					523:530	the C. jejuni proteome	509:530	the C. jejuni proteome	509:530	By using a quantitative proteomic strategy, we were able to monitor changes in the C. jejuni proteome when glycosylation is disrupted.
31015322	1	10	theme	protein	165:171	arg1	control					181:187	protein quality control	165:187	protein quality control	165:187	In eukaryotes, glycosylation plays a role in proteome stability, protein quality control, and modulating protein function; however, similar studies in bacteria are lacking.
31015322	14	11	from	modification	2232:2243	arg1	bacteria					2248:2255	bacteria	2248:2255	bacteria	2248:2255	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	12	12	theme	general	1792:1798	arg1	N-glycosylation					1808:1822	general protein N-glycosylation	1792:1822	general protein N-glycosylation	1792:1822	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	10	13	theme	major	1456:1460	arg1	bacterium					1477:1485	a major food poisoning bacterium	1454:1485	a major food poisoning bacterium	1454:1485	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	13	theme	major	1456:1460	arg1	jejuni					1502:1507	Campylobacter jejuni	1488:1507	Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification	1488:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	1	14	from	studies	240:246	arg1	bacteria					251:258	bacteria	251:258	bacteria	251:258	In eukaryotes, glycosylation plays a role in proteome stability, protein quality control, and modulating protein function; however, similar studies in bacteria are lacking.
31015322	7	15	theme	avian	1040:1044	arg1	host					1046:1049	its natural avian host	1028:1049	its natural avian host	1028:1049	We demonstrate that in vivo, fully glycosylation-deficient C. jejuni bacteria were unable to colonize its natural avian host.
31015322	1	16	theme	protein	205:211	arg1	function					213:220	modulating protein function	194:220	modulating protein function	194:220	In eukaryotes, glycosylation plays a role in proteome stability, protein quality control, and modulating protein function; however, similar studies in bacteria are lacking.
31015322	12	17	theme	proteomic	1767:1775	arg1	results					1777:1783	Our quantitative proteomic results	1750:1783	Our quantitative proteomic results	1750:1783	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	6	18	theme	C.	828:829	arg1	jejuni					831:836	glycosylation-deficient C. jejuni	804:836	glycosylation-deficient C. jejuni	804:836	In glycosylation-deficient C. jejuni, the multidrug efflux pump and electron transport pathways were significantly impaired.
31015322	13	19	theme	host-microbe	2019:2030	arg1	interaction					2032:2042	host-microbe interaction	2019:2042	host-microbe interaction	2019:2042	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	14	20	from	importance	2080:2089	arg1	proteins					2119:2126	proteins	2119:2126	proteins in maintaining bacterial physiology	2119:2162	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	12	21	theme	maintaining	1827:1837	arg1	stability					1848:1856	maintaining proteome stability	1827:1856	maintaining proteome stability	1827:1856	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	3	22	theme	proteomic	454:462	arg1	strategy					464:471	a quantitative proteomic strategy	439:471	a quantitative proteomic strategy	439:471	By using a quantitative proteomic strategy, we were able to monitor changes in the C. jejuni proteome when glycosylation is disrupted.
31015322	4	23	theme	quality	671:677	arg1	control					679:685	protein quality control	663:685	protein quality control	663:685	We demonstrate that in C. jejuni, N-glycosylation is essential to maintain proteome stability and protein quality control.
31015322	7	24	dep	bacteria	995:1002	arg1	jejuni					988:993	fully glycosylation-deficient C. jejuni	955:993	fully glycosylation-deficient C. jejuni	955:993	We demonstrate that in vivo, fully glycosylation-deficient C. jejuni bacteria were unable to colonize its natural avian host.
31015322	5	25	theme	N-glycosylation	740:754	arg1	role					732:735	the role	728:735	the role of N-glycosylation in modulating bacterial cellular activities	728:798	These findings guided us to investigate the role of N-glycosylation in modulating bacterial cellular activities.
31015322	14	26	from	insights	2064:2071	arg1	importance					2080:2089	the importance	2076:2089	the importance of general glycosylation in proteins in maintaining bacterial physiology	2076:2162	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	0	27	theme	Enteric	72:78	arg1	Pathogen					90:97	a Major Enteric Bacterial Pathogen	64:97	a Major Enteric Bacterial Pathogen	64:97	Quantitative Analyses Reveal Novel Roles for N-Glycosylation in a Major Enteric Bacterial Pathogen.
31015322	8	28	dep	system.IMPORTANCE	1190:1206	arg1	Advances					1208:1215	Advances	1208:1215	a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry	1156:1249	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	6	29	theme	glycosylation-deficient	804:826	arg1	jejuni					831:836	glycosylation-deficient C. jejuni	804:836	glycosylation-deficient C. jejuni	804:836	In glycosylation-deficient C. jejuni, the multidrug efflux pump and electron transport pathways were significantly impaired.
31015322	7	30	theme	glycosylation-deficient	961:983	arg1	jejuni					988:993	fully glycosylation-deficient C. jejuni	955:993	fully glycosylation-deficient C. jejuni	955:993	We demonstrate that in vivo, fully glycosylation-deficient C. jejuni bacteria were unable to colonize its natural avian host.
31015322	14	31	theme	bacterial	2143:2151	arg1	physiology					2153:2162	bacterial physiology	2143:2162	bacterial physiology	2143:2162	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	2	32	theme	Campylobacter	382:394	arg1	example					421:427	a well-defined example	406:427	a well-defined example	406:427	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	2	32	theme	Campylobacter	382:394	arg1	jejuni					396:401	the enteropathogen Campylobacter jejuni	363:401	the enteropathogen Campylobacter jejuni	363:401	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	11	33	from	alterations	1711:1721	arg1	proteome					1740:1747	the C. jejuni proteome	1726:1747	the C. jejuni proteome	1726:1747	To achieve this, we employed a quantitative proteomic strategy to monitor alterations in the C. jejuni proteome.
31015322	0	34	from	Roles	35:39	arg1	Pathogen					90:97	a Major Enteric Bacterial Pathogen	64:97	a Major Enteric Bacterial Pathogen	64:97	Quantitative Analyses Reveal Novel Roles for N-Glycosylation in a Major Enteric Bacterial Pathogen.
31015322	14	35	theme	posttranslational	2214:2230	arg1	modification					2232:2243	posttranslational modification	2214:2243	posttranslational modification in bacteria	2214:2255	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	13	36	theme	nitrate	1977:1983	arg1	activity					1995:2002	nitrate reduction activity	1977:2002	nitrate reduction activity	1977:2002	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	0	37	theme	Quantitative	0:11	arg1	Analyses					13:20	Quantitative Analyses	0:20	Quantitative Analyses	0:20	Quantitative Analyses Reveal Novel Roles for N-Glycosylation in a Major Enteric Bacterial Pathogen.
31015322	14	38	theme	emergence	2201:2209	arg1	knowledge					2184:2192	our knowledge	2180:2192	our knowledge of the emergence of posttranslational modification in bacteria	2180:2255	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	2	39	theme	well-defined	408:419	arg1	example					421:427	a well-defined example	406:427	a well-defined example	406:427	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	2	39	theme	well-defined	408:419	arg1	jejuni					396:401	the enteropathogen Campylobacter jejuni	363:401	the enteropathogen Campylobacter jejuni	363:401	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	6	40	theme	transport	878:886	arg1	pathways					888:895	electron transport pathways	869:895	electron transport pathways	869:895	In glycosylation-deficient C. jejuni, the multidrug efflux pump and electron transport pathways were significantly impaired.
31015322	14	41	theme	general	2094:2100	arg1	glycosylation					2102:2114	general glycosylation	2094:2114	general glycosylation	2094:2114	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	10	42	gly	glycosylation	1437:1449	arg1	food					1462:1465	a major food poisoning bacterium	1454:1485	a major food poisoning bacterium	1454:1485	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	42	gly	glycosylation	1437:1449	arg1	poisoning					1467:1475	a major food poisoning bacterium	1454:1485	a major food poisoning bacterium	1454:1485	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	13	43	theme	efflux	1954:1959	arg1	pump					1961:1964	multidrug efflux pump	1944:1964	multidrug efflux pump	1944:1964	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	4	44	theme	proteome	640:647	arg1	stability					649:657	proteome stability	640:657	proteome stability	640:657	We demonstrate that in C. jejuni, N-glycosylation is essential to maintain proteome stability and protein quality control.
31015322	5	45	theme	cellular	780:787	arg1	activities					789:798	bacterial cellular activities	770:798	bacterial cellular activities	770:798	These findings guided us to investigate the role of N-glycosylation in modulating bacterial cellular activities.
31015322	14	46	from	emergence	2201:2209	arg1	bacteria					2248:2255	bacteria	2248:2255	bacteria	2248:2255	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	10	47	from	role	1412:1415	arg1	bacterium					1477:1485	a major food poisoning bacterium	1454:1485	a major food poisoning bacterium	1454:1485	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	47	from	role	1412:1415	arg1	jejuni					1502:1507	Campylobacter jejuni	1488:1507	Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification	1488:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	48	theme	indirect	1562:1569	arg1	effects					1571:1577	the direct and indirect effects	1547:1577	the direct and indirect effects caused by disrupting this posttranslational modification	1547:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	4	49	from	jejuni	591:596	arg1	essential					618:626	essential	618:626	essential	618:626	We demonstrate that in C. jejuni, N-glycosylation is essential to maintain proteome stability and protein quality control.
31015322	2	50	theme	protein	315:321	arg1	systems					337:343	general protein glycosylation systems	307:343	general protein glycosylation systems	307:343	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	6	51	theme	efflux	853:858	arg1	pump					860:863	the multidrug efflux pump	839:863	the multidrug efflux pump	839:863	In glycosylation-deficient C. jejuni, the multidrug efflux pump and electron transport pathways were significantly impaired.
31015322	10	52	theme	direct	1551:1556	arg1	effects					1571:1577	the direct and indirect effects	1547:1577	the direct and indirect effects caused by disrupting this posttranslational modification	1547:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	8	53	theme	complex	1134:1140	arg1	functions					1142:1150	complex functions	1134:1150	complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry	1134:1249	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	11	54	theme	quantitative	1668:1679	arg1	strategy					1691:1698	a quantitative proteomic strategy	1666:1698	a quantitative proteomic strategy to monitor alterations in the C. jejuni proteome	1666:1747	To achieve this, we employed a quantitative proteomic strategy to monitor alterations in the C. jejuni proteome.
31015322	13	55	theme	bacterial	1904:1912	arg1	N-glycosylation					1914:1928	bacterial N-glycosylation	1904:1928	bacterial N-glycosylation	1904:1928	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	2	56	theme	systems	337:343	arg1	roles					298:302	the roles	294:302	the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example	294:427	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	1	57	theme	similar	232:238	arg1	studies					240:246	similar studies	232:246	similar studies in bacteria	232:258	In eukaryotes, glycosylation plays a role in proteome stability, protein quality control, and modulating protein function; however, similar studies in bacteria are lacking.
31015322	8	58	theme	bacterial	1158:1166	arg1	system.IMPORTANCE					1190:1206	a bacterial general glycosylation system.IMPORTANCE	1156:1206	a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry	1156:1249	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	12	59	theme	proteome	1839:1846	arg1	stability					1848:1856	maintaining proteome stability	1827:1856	maintaining proteome stability	1827:1856	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	12	60	attach	linked	1785:1790	arg2	results					1777:1783	Our quantitative proteomic results	1750:1783	Our quantitative proteomic results	1750:1783	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	12	60	attach	linked	1785:1790	arg1	stability					1848:1856	maintaining proteome stability	1827:1856	maintaining proteome stability	1827:1856	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	13	61	theme	Functional	1859:1868	arg1	analyses					1870:1877	Functional analyses	1859:1877	Functional analyses	1859:1877	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	10	62	theme	glycosylation	1437:1449	arg1	role					1412:1415	the role	1408:1415	the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification	1408:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	3	63	theme	jejuni	516:521	arg1	proteome					523:530	the C. jejuni proteome	509:530	the C. jejuni proteome	509:530	By using a quantitative proteomic strategy, we were able to monitor changes in the C. jejuni proteome when glycosylation is disrupted.
31015322	8	64	theme	glycosylation	1176:1188	arg1	system.IMPORTANCE					1190:1206	a bacterial general glycosylation system.IMPORTANCE	1156:1206	a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry	1156:1249	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	8	65	from	types	1273:1277	arg1	bacteria					1307:1314	bacteria	1307:1314	bacteria	1307:1314	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	10	66	theme	posttranslational	1605:1621	arg1	modification					1623:1634	this posttranslational modification	1600:1634	this posttranslational modification	1600:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	11	67	theme	C.	1730:1731	arg1	proteome					1740:1747	the C. jejuni proteome	1726:1747	the C. jejuni proteome	1726:1747	To achieve this, we employed a quantitative proteomic strategy to monitor alterations in the C. jejuni proteome.
31015322	10	68	theme	general	1420:1426	arg1	glycosylation					1437:1449	general N-linked glycosylation	1420:1449	general N-linked glycosylation	1420:1449	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	12	69	theme	protein	1800:1806	arg1	N-glycosylation					1808:1822	general protein N-glycosylation	1792:1822	general protein N-glycosylation	1792:1822	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	10	70	link	N-linked	1428:1435	arg1	glycosylation					1437:1449	general N-linked glycosylation	1420:1449	general N-linked glycosylation	1420:1449	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	71	theme	food	1462:1465	arg1	bacterium					1477:1485	a major food poisoning bacterium	1454:1485	a major food poisoning bacterium	1454:1485	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	71	theme	food	1462:1465	arg1	jejuni					1502:1507	Campylobacter jejuni	1488:1507	Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification	1488:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	1	72	theme	quality	173:179	arg1	control					181:187	protein quality control	165:187	protein quality control	165:187	In eukaryotes, glycosylation plays a role in proteome stability, protein quality control, and modulating protein function; however, similar studies in bacteria are lacking.
31015322	8	73	theme	systems	1296:1302	arg1	types					1273:1277	several types	1265:1277	several types of glycosylation systems in bacteria	1265:1314	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	4	74	from	essential	618:626	arg1	jejuni					591:596	C. jejuni	588:596	C. jejuni	588:596	We demonstrate that in C. jejuni, N-glycosylation is essential to maintain proteome stability and protein quality control.
31015322	8	75	theme	mass	1233:1236	arg1	spectrometry					1238:1249	mass spectrometry	1233:1249	mass spectrometry	1233:1249	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	1	76	theme	modulating	194:203	arg1	function					213:220	modulating protein function	194:220	modulating protein function	194:220	In eukaryotes, glycosylation plays a role in proteome stability, protein quality control, and modulating protein function; however, similar studies in bacteria are lacking.
31015322	8	77	from	systems	1296:1302	arg1	bacteria					1307:1314	bacteria	1307:1314	bacteria	1307:1314	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	8	78	theme	several	1265:1271	arg1	types					1273:1277	several types	1265:1277	several types of glycosylation systems in bacteria	1265:1314	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	6	79	theme	multidrug	843:851	arg1	pump					860:863	the multidrug efflux pump	839:863	the multidrug efflux pump	839:863	In glycosylation-deficient C. jejuni, the multidrug efflux pump and electron transport pathways were significantly impaired.
31015322	7	80	theme	natural	1032:1038	arg1	host					1046:1049	its natural avian host	1028:1049	its natural avian host	1028:1049	We demonstrate that in vivo, fully glycosylation-deficient C. jejuni bacteria were unable to colonize its natural avian host.
31015322	12	81	theme	quantitative	1754:1765	arg1	results					1777:1783	Our quantitative proteomic results	1750:1783	Our quantitative proteomic results	1750:1783	Our quantitative proteomic results linked general protein N-glycosylation to maintaining proteome stability.
31015322	0	82	theme	Major	66:70	arg1	Pathogen					90:97	a Major Enteric Bacterial Pathogen	64:97	a Major Enteric Bacterial Pathogen	64:97	Quantitative Analyses Reveal Novel Roles for N-Glycosylation in a Major Enteric Bacterial Pathogen.
31015322	4	83	theme	protein	663:669	arg1	control					679:685	protein quality control	663:685	protein quality control	663:685	We demonstrate that in C. jejuni, N-glycosylation is essential to maintain proteome stability and protein quality control.
31015322	13	84	theme	reduction	1985:1993	arg1	activity					1995:2002	nitrate reduction activity	1977:2002	nitrate reduction activity	1977:2002	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	0	85	theme	Bacterial	80:88	arg1	Pathogen					90:97	a Major Enteric Bacterial Pathogen	64:97	a Major Enteric Bacterial Pathogen	64:97	Quantitative Analyses Reveal Novel Roles for N-Glycosylation in a Major Enteric Bacterial Pathogen.
31015322	9	86	theme	bacterial	1330:1338	arg1	proteins					1340:1347	bacterial proteins	1330:1347	bacterial proteins	1330:1347	However, why bacterial proteins are modified remains poorly defined.
31015322	8	87	from	bacteria	1307:1314	arg1	types					1273:1277	several types	1265:1277	several types of glycosylation systems in bacteria	1265:1314	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	1	88	theme	proteome	145:152	arg1	stability					154:162	proteome stability	145:162	proteome stability	145:162	In eukaryotes, glycosylation plays a role in proteome stability, protein quality control, and modulating protein function; however, similar studies in bacteria are lacking.
31015322	10	89	theme	Campylobacter	1488:1500	arg1	bacterium					1477:1485	a major food poisoning bacterium	1454:1485	a major food poisoning bacterium	1454:1485	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	10	89	theme	Campylobacter	1488:1500	arg1	jejuni					1502:1507	Campylobacter jejuni	1488:1507	Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification	1488:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	8	90	theme	first	1078:1082	arg1	evidence					1084:1091	the first evidence	1074:1091	the first evidence of a link between proteome stability	1074:1128	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	7	91	theme	C.	985:986	arg1	jejuni					988:993	fully glycosylation-deficient C. jejuni	955:993	fully glycosylation-deficient C. jejuni	955:993	We demonstrate that in vivo, fully glycosylation-deficient C. jejuni bacteria were unable to colonize its natural avian host.
31015322	14	92	theme	modification	2232:2243	arg1	emergence					2201:2209	the emergence	2197:2209	the emergence of posttranslational modification in bacteria	2197:2255	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	2	93	theme	enteropathogen	367:380	arg1	example					421:427	a well-defined example	406:427	a well-defined example	406:427	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	2	93	theme	enteropathogen	367:380	arg1	jejuni					396:401	the enteropathogen Campylobacter jejuni	363:401	the enteropathogen Campylobacter jejuni	363:401	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	0	94	theme	Novel	29:33	arg1	Roles					35:39	Novel Roles	29:39	Novel Roles for N-Glycosylation in a Major Enteric Bacterial Pathogen	29:97	Quantitative Analyses Reveal Novel Roles for N-Glycosylation in a Major Enteric Bacterial Pathogen.
31015322	8	95	theme	link	1098:1101	arg1	evidence					1084:1091	the first evidence	1074:1091	the first evidence of a link between proteome stability	1074:1128	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	14	96	theme	glycosylation	2102:2114	arg1	importance					2080:2089	the importance	2076:2089	the importance of general glycosylation in proteins in maintaining bacterial physiology	2076:2162	This work provides insights on the importance of general glycosylation in proteins in maintaining bacterial physiology, thus expanding our knowledge of the emergence of posttranslational modification in bacteria.
31015322	13	97	theme	multidrug	1944:1952	arg1	pump					1961:1964	multidrug efflux pump	1944:1964	multidrug efflux pump	1944:1964	Functional analyses revealed novel roles for bacterial N-glycosylation in modulating multidrug efflux pump, enhancing nitrate reduction activity, and promoting host-microbe interaction.
31015322	5	98	theme	bacterial	770:778	arg1	activities					789:798	bacterial cellular activities	770:798	bacterial cellular activities	770:798	These findings guided us to investigate the role of N-glycosylation in modulating bacterial cellular activities.
31015322	8	99	theme	proteome	1111:1118	arg1	stability					1120:1128	proteome stability	1111:1128	proteome stability	1111:1128	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	6	100	theme	electron	869:876	arg1	pathways					888:895	electron transport pathways	869:895	electron transport pathways	869:895	In glycosylation-deficient C. jejuni, the multidrug efflux pump and electron transport pathways were significantly impaired.
31015322	10	101	theme	study	1525:1529	arg1	aim					1513:1515	The aim	1509:1515	The aim of this study	1509:1529	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	11	102	theme	jejuni	1733:1738	arg1	proteome					1740:1747	the C. jejuni proteome	1726:1747	the C. jejuni proteome	1726:1747	To achieve this, we employed a quantitative proteomic strategy to monitor alterations in the C. jejuni proteome.
31015322	3	103	theme	quantitative	441:452	arg1	strategy					464:471	a quantitative proteomic strategy	439:471	a quantitative proteomic strategy	439:471	By using a quantitative proteomic strategy, we were able to monitor changes in the C. jejuni proteome when glycosylation is disrupted.
31015322	10	104	dep	jejuni	1502:1507	arg1	is					1531:1532	is	1531:1532	is to delineate the direct and indirect effects caused by disrupting this posttranslational modification	1531:1634	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
31015322	2	105	theme	general	307:313	arg1	systems					337:343	general protein glycosylation systems	307:343	general protein glycosylation systems	307:343	Here, we investigate the roles of general protein glycosylation systems in bacteria using the enteropathogen Campylobacter jejuni as a well-defined example.
31015322	8	106	from	Advances	1208:1215	arg1	genomics					1220:1227	genomics	1220:1227	genomics	1220:1227	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	8	106	from	Advances	1208:1215	arg1	spectrometry					1238:1249	mass spectrometry	1233:1249	mass spectrometry	1233:1249	These results provide the first evidence of a link between proteome stability and complex functions via a bacterial general glycosylation system.IMPORTANCE Advances in genomics and mass spectrometry have revealed several types of glycosylation systems in bacteria.
31015322	4	107	theme	C.	588:589	arg1	jejuni					591:596	C. jejuni	588:596	C. jejuni	588:596	We demonstrate that in C. jejuni, N-glycosylation is essential to maintain proteome stability and protein quality control.
31015322	10	108	theme	N-linked	1428:1435	arg1	glycosylation					1437:1449	general N-linked glycosylation	1420:1449	general N-linked glycosylation	1420:1449	Here, we investigated the role of general N-linked glycosylation in a major food poisoning bacterium, Campylobacter jejuni The aim of this study is to delineate the direct and indirect effects caused by disrupting this posttranslational modification.
30814666	0	0	theme	phenotypic	75:84	arg1	diversity					86:94	phenotypic diversity	75:94	phenotypic diversity	75:94	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	1	1	theme	regulatory	162:171	arg1	modifications					213:225	post-translational modifications	194:225	post-translational modifications (PTMs)	194:232	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	1	1	theme	regulatory	162:171	arg1	mechanisms					173:182	Multiple regulatory mechanisms	153:182	Multiple regulatory mechanisms including post-translational modifications (PTMs)	153:232	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	0	2	from	glycosylation	6:18	arg1	membrane					23:30	membrane	23:30	membrane	23:30	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	0	2	from	glycosylation	6:18	arg1	proteins					50:57	cell envelope proteins	36:57	cell envelope proteins	36:57	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	5	3	theme	data	659:662	arg1	set					664:666	This data set	654:666	This data set	654:666	This data set represents the highest number of glycosylated proteins identified in Mtb to date.
30814666	10	4	theme	differential	1419:1430	arg1	pattern					1446:1452	The differential glycosylation pattern	1415:1452	The differential glycosylation pattern	1415:1452	The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages.
30814666	7	5	gly	glycosylation	897:909	arg1	Mtb					914:916	Mtb	914:916	Mtb	914:916	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	7	5	gly	glycosylation	897:909	arg1	bacteria					939:946	Gram-positive bacteria	925:946	Gram-positive bacteria	925:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	8	6	theme	fatty	1037:1041	arg1	acid					1043:1046	fatty acid and lipid metabolism	1037:1067	acid	1043:1046	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	3	7	theme	glycoproteomic	408:421	arg1	patterns					423:430	The glycoproteomic patterns	404:430	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7	404:540	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	7	8	theme	first	864:868	arg1	report					870:875	the first report	860:875	the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria	860:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	7	8	theme	first	864:868	arg1	This					852:855	This	852:855	This	852:855	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	4	9	theme	2944	594:597	arg1	events					613:618	2944 glycosylation events	594:618	2944 glycosylation events	594:618	A total of 2944 glycosylation events were discovered in 1325 proteins.
30814666	10	10	theme	glycosylation	1432:1444	arg1	pattern					1446:1452	The differential glycosylation pattern	1415:1452	The differential glycosylation pattern	1415:1452	The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages.
30814666	8	11	theme	Mtb glycoproteins	975:991	arg1	bulk					967:970	the bulk	963:970	the bulk of Mtb glycoproteins	963:991	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	1	12	theme	Mycobacterium	292:304	arg1	Mtb					320:322	Mtb	320:322	Mtb	320:322	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	1	12	theme	Mycobacterium	292:304	arg1	tuberculosis					306:317	Mycobacterium tuberculosis	292:317	Mycobacterium tuberculosis (Mtb)	292:323	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	8	13	dep	exposed	1147:1153	arg1	surface					1139:1145	surface	1139:1145	surface	1139:1145	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	9	14	theme	Quantitative	1184:1195	arg1	analysis					1212:1219	Quantitative glycoproteomic analysis	1184:1219	Quantitative glycoproteomic analysis	1184:1219	Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins.
30814666	7	15	from	report	870:875	arg1	glycosylation					897:909	N-linked protein glycosylation	880:909	N-linked protein glycosylation in Mtb and in Gram-positive bacteria	880:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	3	16	theme	Mycobacterium	460:472	arg1	MTBC					496:499	MTBC	496:499	MTBC	496:499	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	3	16	theme	Mycobacterium	460:472	arg1	complex					487:493	the Mycobacterium tuberculosis complex	456:493	the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7	456:540	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	9	17	from	sites	1239:1243	arg1	proteins					1251:1258	67 proteins	1248:1258	67 proteins involved in Mtb fitness and survival	1248:1295	Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins.
30814666	3	18	theme	clinical	435:442	arg1	isolates					444:451	clinical isolates	435:451	clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7	435:540	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	9	19	theme	glycoproteomic	1197:1210	arg1	analysis					1212:1219	Quantitative glycoproteomic analysis	1184:1219	Quantitative glycoproteomic analysis	1184:1219	Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins.
30814666	0	20	dep	diversity	86:94	arg1	the					71:73	the	71:73	the	71:73	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	1	21	theme	post-translational	194:211	arg1	modifications					213:225	post-translational modifications	194:225	post-translational modifications (PTMs)	194:232	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	1	21	theme	post-translational	194:211	arg1	PTMs					228:231	PTMs	228:231	PTMs	228:231	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	9	22	theme	Mtb	1272:1274	arg1	fitness					1276:1282	Mtb fitness	1272:1282	Mtb fitness	1272:1282	Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins.
30814666	10	23	theme	phenotypic	1472:1481	arg1	variabilities					1483:1495	phenotypic variabilities	1472:1495	phenotypic variabilities across Mtb lineages	1472:1515	The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages.
30814666	6	24	theme	events	789:794	arg1	events					789:794	the events	785:794	the events identified	785:805	O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated.
30814666	6	24	theme	events	789:794	arg1	%					780:780	83%	778:780	83% of the events identified	778:805	O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated.
30814666	8	25	theme	two-component	1070:1082	arg1	systems					1084:1090	two-component systems	1070:1090	two-component systems	1070:1090	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	0	26	theme	Ample	0:4	arg1	glycosylation					6:18	Ample glycosylation	0:18	Ample glycosylation in membrane and cell envelope proteins	0:57	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	1	27	theme	tuberculosis	306:317	arg1	proteomes					279:287	proteomes	279:287	proteomes	279:287	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	1	27	theme	tuberculosis	306:317	arg1	genomes					267:273	simpler genomes	259:273	simpler genomes	259:273	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	8	28	theme	lipid	1052:1056	arg1	metabolism					1058:1067	fatty acid and lipid metabolism	1037:1067	metabolism	1058:1067	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	8	29	theme	cell	1009:1012	arg1	biosynthesis					1023:1034	cell envelope biosynthesis	1009:1034	cell envelope biosynthesis	1009:1034	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	8	30	theme	envelope	1014:1021	arg1	biosynthesis					1023:1034	cell envelope biosynthesis	1009:1034	cell envelope biosynthesis	1009:1034	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	10	31	theme	Mtb	1504:1506	arg1	lineages					1508:1515	Mtb lineages	1504:1515	Mtb lineages	1504:1515	The differential glycosylation pattern may contribute to phenotypic variabilities across Mtb lineages.
30814666	0	32	theme	Mycobacterium	117:129	arg1	complex					144:150	the Mycobacterium tuberculosis complex	113:150	the Mycobacterium tuberculosis complex	113:150	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	7	33	from	glycosylation	897:909	arg1	Mtb					914:916	Mtb	914:916	Mtb	914:916	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	7	33	from	glycosylation	897:909	arg1	bacteria					939:946	Gram-positive bacteria	925:946	Gram-positive bacteria	925:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	4	34	theme	1325	639:642	arg1	proteins					644:651	1325 proteins	639:651	1325 proteins	639:651	A total of 2944 glycosylation events were discovered in 1325 proteins.
30814666	8	35	gly	Mtb glycoproteins	975:991	arg1	Mtb glycoproteins					975:991	Mtb glycoproteins	975:991	Mtb glycoproteins	975:991	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	5	36	theme	proteins	714:721	arg1	number					691:696	the highest number	679:696	the highest number of glycosylated proteins identified in Mtb to date	679:747	This data set represents the highest number of glycosylated proteins identified in Mtb to date.
30814666	3	37	theme	mass	564:567	arg1	spectrometry					569:580	mass spectrometry	564:580	mass spectrometry	564:580	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	6	38	gly	N-glycosylated	836:849	arg1	sites					825:829	the sites	821:829	the sites	821:829	O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated.
30814666	6	38	gly	N-glycosylated	836:849	arg1	%					816:816	17%	814:816	17% of the sites	814:829	O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated.
30814666	9	39	gly	glycosylated	1317:1328	arg1	sites					1239:1243	101 sites	1235:1243	101 sites on 67 proteins involved in Mtb fitness and survival	1235:1295	Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins.
30814666	0	40	theme	cell	36:39	arg1	proteins					50:57	cell envelope proteins	36:57	cell envelope proteins	36:57	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	1	41	dep	genomes	267:273	arg1	the					255:257	the	255:257	the	255:257	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	7	42	theme	protein	889:895	arg1	glycosylation					897:909	N-linked protein glycosylation	880:909	N-linked protein glycosylation in Mtb and in Gram-positive bacteria	880:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	3	43	theme	complex	487:493	arg1	isolates					444:451	clinical isolates	435:451	clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7	435:540	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	3	44	theme	isolates	444:451	arg1	patterns					423:430	The glycoproteomic patterns	404:430	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7	404:540	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	0	45	theme	tuberculosis	131:142	arg1	complex					144:150	the Mycobacterium tuberculosis complex	113:150	the Mycobacterium tuberculosis complex	113:150	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	0	46	gly	glycosylation	6:18	arg1	membrane					23:30	membrane	23:30	membrane	23:30	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	0	46	gly	glycosylation	6:18	arg1	proteins					50:57	cell envelope proteins	36:57	cell envelope proteins	36:57	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	8	47	theme	pathogen-host	1097:1109	arg1	interaction					1111:1121	pathogen-host interaction	1097:1121	pathogen-host interaction that are either surface exposed or located in the cell wall	1097:1181	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	2	48	theme	significant	360:370	arg1	role					372:375	a significant role	358:375	a significant role	358:375	PTMs such as glycosylation play a significant role in Mtb adaptive processes.
30814666	0	49	theme	envelope	41:48	arg1	proteins					50:57	cell envelope proteins	36:57	cell envelope proteins	36:57	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	5	50	theme	highest	683:689	arg1	number					691:696	the highest number	679:696	the highest number of glycosylated proteins identified in Mtb to date	679:747	This data set represents the highest number of glycosylated proteins identified in Mtb to date.
30814666	7	51	link	N-linked	880:887	arg1	glycosylation					897:909	N-linked protein glycosylation	880:909	N-linked protein glycosylation in Mtb and in Gram-positive bacteria	880:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	6	52	theme	sites	825:829	arg1	sites					825:829	the sites	821:829	the sites	821:829	O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated.
30814666	6	52	theme	sites	825:829	arg1	%					816:816	17%	814:816	17% of the sites	814:829	O-glycosylation constituted 83% of the events identified, while 17% of the sites were N-glycosylated.
30814666	5	53	gly	glycosylated	701:712	arg1	proteins					714:721	glycosylated proteins	701:721	glycosylated proteins identified in Mtb to date	701:747	This data set represents the highest number of glycosylated proteins identified in Mtb to date.
30814666	11	54	dep	important	1558:1566	arg1	membrane-associated					1568:1586	membrane-associated	1568:1586	membrane-associated	1568:1586	The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.
30814666	0	55	from	virulence	100:108	arg1	complex					144:150	the Mycobacterium tuberculosis complex	113:150	the Mycobacterium tuberculosis complex	113:150	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	11	56	theme	important	1558:1566	arg1	glycolipoproteins					1588:1604	several clinically important membrane-associated glycolipoproteins	1539:1604	several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery	1539:1680	The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.
30814666	9	57	theme	cell	1378:1381	arg1	envelope					1383:1390	cell envelope and membrane proteins	1378:1412	envelope	1383:1390	Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins.
30814666	4	58	theme	events	613:618	arg1	total					585:589	A total	583:589	A total of 2944 glycosylation events	583:618	A total of 2944 glycosylation events were discovered in 1325 proteins.
30814666	8	59	from	wall	1178:1181	arg1	located					1158:1164	located	1158:1164	located	1158:1164	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	8	60	from	located	1158:1164	arg1	wall					1178:1181	the cell wall	1169:1181	the cell wall	1169:1181	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	8	61	theme	cell	1173:1176	arg1	wall					1178:1181	the cell wall	1169:1181	the cell wall	1169:1181	Collectively, the bulk of Mtb glycoproteins are involved in cell envelope biosynthesis, fatty acid and lipid metabolism, two-component systems, and pathogen-host interaction that are either surface exposed or located in the cell wall.
30814666	11	62	theme	vaccine	1664:1670	arg1	discovery					1672:1680	drug and vaccine discovery	1655:1680	drug and vaccine discovery	1655:1680	The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.
30814666	1	63	theme	Multiple	153:160	arg1	modifications					213:225	post-translational modifications	194:225	post-translational modifications (PTMs)	194:232	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	1	63	theme	Multiple	153:160	arg1	mechanisms					173:182	Multiple regulatory mechanisms	153:182	Multiple regulatory mechanisms including post-translational modifications (PTMs)	153:232	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	7	64	theme	N-linked	880:887	arg1	glycosylation					897:909	N-linked protein glycosylation	880:909	N-linked protein glycosylation in Mtb and in Gram-positive bacteria	880:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	4	65	theme	glycosylation	599:611	arg1	events					613:618	2944 glycosylation events	594:618	2944 glycosylation events	594:618	A total of 2944 glycosylation events were discovered in 1325 proteins.
30814666	0	66	from	diversity	86:94	arg1	complex					144:150	the Mycobacterium tuberculosis complex	113:150	the Mycobacterium tuberculosis complex	113:150	Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.
30814666	2	67	theme	adaptive	384:391	arg1	processes					393:401	Mtb adaptive processes	380:401	Mtb adaptive processes	380:401	PTMs such as glycosylation play a significant role in Mtb adaptive processes.
30814666	3	68	theme	tuberculosis	474:485	arg1	MTBC					496:499	MTBC	496:499	MTBC	496:499	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	3	68	theme	tuberculosis	474:485	arg1	complex					487:493	the Mycobacterium tuberculosis complex	456:493	the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7	456:540	The glycoproteomic patterns of clinical isolates of the Mycobacterium tuberculosis complex (MTBC) representing the lineages 3, 4, 5 and 7 were characterized by mass spectrometry.
30814666	1	69	theme	simpler	259:265	arg1	genomes					267:273	simpler genomes	259:273	simpler genomes	259:273	Multiple regulatory mechanisms including post-translational modifications (PTMs) confer complexity to the simpler genomes and proteomes of Mycobacterium tuberculosis (Mtb).
30814666	7	70	theme	Gram-positive	925:937	arg1	bacteria					939:946	Gram-positive bacteria	925:946	Gram-positive bacteria	925:946	This is the first report on N-linked protein glycosylation in Mtb and in Gram-positive bacteria.
30814666	5	71	theme	glycosylated	701:712	arg1	proteins					714:721	glycosylated proteins	701:721	glycosylated proteins identified in Mtb to date	701:747	This data set represents the highest number of glycosylated proteins identified in Mtb to date.
30814666	11	72	theme	drug	1655:1658	arg1	discovery					1672:1680	drug and vaccine discovery	1655:1680	drug and vaccine discovery	1655:1680	The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.
30814666	2	73	theme	Mtb	380:382	arg1	processes					393:401	Mtb adaptive processes	380:401	Mtb adaptive processes	380:401	PTMs such as glycosylation play a significant role in Mtb adaptive processes.
30814666	11	74	theme	several	1539:1545	arg1	glycolipoproteins					1588:1604	several clinically important membrane-associated glycolipoproteins	1539:1604	several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery	1539:1680	The study identified several clinically important membrane-associated glycolipoproteins that are relevant for diagnostics as well as for drug and vaccine discovery.
30814666	9	75	theme	membrane	1396:1403	arg1	proteins					1405:1412	cell envelope and membrane proteins	1378:1412	proteins	1405:1412	Quantitative glycoproteomic analysis revealed that 101 sites on 67 proteins involved in Mtb fitness and survival were differentially glycosylated between the four lineages, among which 64% were cell envelope and membrane proteins.
28652091	0	0	theme	analytical	91:100	arg1	studies					102:108	solid-state and analytical studies	75:108	solid-state and analytical studies	75:108	Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.
28652091	8	1	theme	well-identified	1268:1282	arg1	sites					1300:1304	well-identified TIC interaction sites	1268:1304	well-identified TIC interaction sites	1268:1304	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	6	2	theme	ASA	1016:1018	arg1	cocrystals					994:1003	No cocrystals	991:1003	No cocrystals of TIC and ASA	991:1018	No cocrystals of TIC and ASA have been found.
28652091	4	3	theme	liquid	601:606	arg1	spectrometry					655:666	liquid chromatography-high resolution-multistage mass spectrometry	601:666	liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn)	601:678	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	4	3	theme	liquid	601:606	arg1	LC-HR-MSn					669:677	LC-HR-MSn	669:677	LC-HR-MSn	669:677	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	8	4	theme	decomposition	1161:1173	arg1	mechanism					1175:1183	The decomposition mechanism	1157:1183	The decomposition mechanism in the liquid phase	1157:1203	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	7	5	theme	pharmaceuticals	1140:1154	arg1	instability					1117:1127	chemical instability	1108:1127	chemical instability of the two pharmaceuticals	1108:1154	The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals.
28652091	8	6	theme	liquid	1192:1197	arg1	phase					1199:1203	the liquid phase	1188:1203	the liquid phase	1188:1203	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	4	7	theme	thermogravimetric	756:772	arg1	analysis					774:781	thermogravimetric analysis	756:781	thermogravimetric analysis	756:781	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	8	8	from	mechanism	1175:1183	arg1	phase					1199:1203	the liquid phase	1188:1203	the liquid phase	1188:1203	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	10	9	theme	important	1416:1424	arg1	N-dealkylation					1449:1462	N-dealkylation	1449:1462	N-dealkylation	1449:1462	The most important degradation pathway is N-dealkylation.
28652091	10	9	theme	important	1416:1424	arg1	pathway					1438:1444	The most important degradation pathway	1407:1444	The most important degradation pathway	1407:1444	The most important degradation pathway is N-dealkylation.
28652091	11	10	theme	ASA	1553:1555	arg1	decomposition					1536:1548	the decomposition	1532:1548	the decomposition of ASA	1532:1555	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	4	11	theme	resolution-multistage	628:648	arg1	spectrometry					655:666	liquid chromatography-high resolution-multistage mass spectrometry	601:666	liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn)	601:678	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	4	11	theme	resolution-multistage	628:648	arg1	LC-HR-MSn					669:677	LC-HR-MSn	669:677	LC-HR-MSn	669:677	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	2	12	theme	patient	282:288	arg1	adherence					290:298	patient adherence	282:298	patient adherence to such treatments	282:317	To improve patient adherence to such treatments, combination therapies (polypill) are envisioned.
28652091	3	13	theme	antagonist	495:504	arg1	Ticagrelor					506:515	the P2Y12-receptor antagonist Ticagrelor	476:515	the P2Y12-receptor antagonist Ticagrelor (TIC)	476:521	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	3	13	theme	antagonist	495:504	arg1	TIC					518:520	TIC	518:520	TIC	518:520	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	1	14	with	patients	138:145	arg1	syndrome					167:174	acute coronary syndrome	152:174	acute coronary syndrome	152:174	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	5	15	theme	0.457	869:873	arg1	liquid					859:864	liquid	859:864	liquid	859:864	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	5	16	theme	TIC	919:921	arg1	molecules					923:931	TIC molecules	919:931	TIC molecules in each other's crystal structures	919:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	3	17	theme	preformulation	440:453	arg1	strategy					455:462	a preformulation strategy	438:462	a preformulation strategy of ASA	438:469	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	4	18	theme	chromatography-high	608:626	arg1	spectrometry					655:666	liquid chromatography-high resolution-multistage mass spectrometry	601:666	liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn)	601:678	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	4	18	theme	chromatography-high	608:626	arg1	LC-HR-MSn					669:677	LC-HR-MSn	669:677	LC-HR-MSn	669:677	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	7	19	theme	instability	1117:1127	arg1	onset					1099:1103	a clear onset	1091:1103	a clear onset of chemical instability of the two pharmaceuticals	1091:1154	The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals.
28652091	11	20	theme	high	1612:1615	arg1	humidity					1617:1624	high humidity	1612:1624	high humidity	1612:1624	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	1	21	theme	oral	182:185	arg1	route					187:191	an oral route	179:191	an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA)	179:268	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	0	22	theme	therapeutic	14:24	arg1	usage					26:30	therapeutic usage	14:30	therapeutic usage of combined Ticagrelor and Aspirin	14:65	Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.
28652091	4	23	dep	using	560:564	arg1	transform					720:728	transform	720:728	transform infrared measurements and thermogravimetric analysis	720:781	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	9	24	theme	corresponding	1371:1383	arg1	products					1397:1404	corresponding degradation products	1371:1404	corresponding degradation products	1371:1404	Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products.
28652091	11	25	theme	ASA	1493:1495	arg1	approach					1518:1525	a viable approach	1509:1525	a viable approach	1509:1525	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	11	25	theme	ASA	1493:1495	arg1	polypills					1480:1488	polypills	1480:1488	polypills of ASA and TIC	1480:1503	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	1	26	theme	route	187:191	arg1	therapy					211:217	an oral route dual antiplatelet therapy	179:217	an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA)	179:268	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	1	26	theme	route	187:191	arg1	treatment					124:132	The mainstay treatment	111:132	The mainstay treatment for patients with acute coronary syndrome	111:174	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	4	27	theme	differential	566:577	arg1	calorimetry					588:598	differential scanning calorimetry	566:598	differential scanning calorimetry	566:598	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	5	28	theme	ASA	911:913	arg1	mixing					901:906	the mixing	897:906	the mixing of ASA and TIC molecules in each other's crystal structures	897:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	7	29	theme	chemical	1108:1115	arg1	instability					1117:1127	chemical instability	1108:1127	chemical instability of the two pharmaceuticals	1108:1154	The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals.
28652091	9	30	attach	linked	1361:1366	arg1	products					1397:1404	corresponding degradation products	1371:1404	corresponding degradation products	1371:1404	Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products.
28652091	9	30	attach	linked	1361:1366	arg2	LC-HR-MSn					1351:1359	LC-HR-MSn	1351:1359	LC-HR-MSn linked to corresponding degradation products	1351:1404	Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products.
28652091	1	31	theme	dual	193:196	arg1	therapy					211:217	an oral route dual antiplatelet therapy	179:217	an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA)	179:268	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	1	31	theme	dual	193:196	arg1	treatment					124:132	The mainstay treatment	111:132	The mainstay treatment for patients with acute coronary syndrome	111:174	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	3	32	theme	Physicochemical	369:383	arg1	studies					397:403	Physicochemical solid-state studies	369:403	Physicochemical solid-state studies	369:403	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	6	33	theme	TIC	1008:1010	arg1	cocrystals					994:1003	No cocrystals	991:1003	No cocrystals of TIC and ASA	991:1018	No cocrystals of TIC and ASA have been found.
28652091	5	34	from	structures	957:966	arg1	mixing					901:906	the mixing	897:906	the mixing of ASA and TIC molecules in each other's crystal structures	897:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	2	35	theme	such	303:306	arg1	treatments					308:317	such treatments	303:317	such treatments	303:317	To improve patient adherence to such treatments, combination therapies (polypill) are envisioned.
28652091	1	36	theme	antiplatelet	198:209	arg1	therapy					211:217	an oral route dual antiplatelet therapy	179:217	an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA)	179:268	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	1	36	theme	antiplatelet	198:209	arg1	treatment					124:132	The mainstay treatment	111:132	The mainstay treatment for patients with acute coronary syndrome	111:174	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	3	37	theme	solid-state	385:395	arg1	studies					397:403	Physicochemical solid-state studies	369:403	Physicochemical solid-state studies	369:403	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	7	38	theme	clear	1093:1097	arg1	onset					1099:1103	a clear onset	1091:1103	a clear onset of chemical instability of the two pharmaceuticals	1091:1154	The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals.
28652091	5	39	from	98°C	816:819	arg1	transition					802:811	A simple eutectic transition	784:811	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457	784:873	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	1	40	theme	mainstay	115:122	arg1	therapy					211:217	an oral route dual antiplatelet therapy	179:217	an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA)	179:268	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	1	40	theme	mainstay	115:122	arg1	treatment					124:132	The mainstay treatment	111:132	The mainstay treatment for patients with acute coronary syndrome	111:174	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	8	41	theme	interaction	1288:1298	arg1	sites					1300:1304	well-identified TIC interaction sites	1268:1304	well-identified TIC interaction sites	1268:1304	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	0	42	theme	Ticagrelor	44:53	arg1	usage					26:30	therapeutic usage	14:30	therapeutic usage of combined Ticagrelor and Aspirin	14:65	Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.
28652091	4	43	theme	scanning	579:586	arg1	calorimetry					588:598	differential scanning calorimetry	566:598	differential scanning calorimetry	566:598	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	5	44	theme	simple	786:791	arg1	transition					802:811	A simple eutectic transition	784:811	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457	784:873	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	5	45	with	98°C	816:819	arg1	fraction					833:840	a mole fraction	826:840	a mole fraction for the eutectic liquid of 0.457	826:873	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	5	46	theme	molecules	923:931	arg1	mixing					901:906	the mixing	897:906	the mixing of ASA and TIC molecules in each other's crystal structures	897:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	4	47	theme	complementary	687:699	arg1	techniques					701:710	as complementary techniques	684:710	as complementary techniques	684:710	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	0	48	theme	combined	35:42	arg1	Ticagrelor					44:53	combined Ticagrelor	35:53	combined Ticagrelor	35:53	Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.
28652091	1	49	with	therapy	211:217	arg1	ASA					265:267	ASA	265:267	ASA	265:267	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	1	49	with	therapy	211:217	arg1	Aspirin					256:262	Aspirin	256:262	Aspirin (ASA)	256:268	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	1	49	with	therapy	211:217	arg1	antagonist					241:250	a P2Y12-receptor antagonist	224:250	a P2Y12-receptor antagonist	224:250	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	11	50	theme	TIC	1501:1503	arg1	approach					1518:1525	a viable approach	1509:1525	a viable approach	1509:1525	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	11	50	theme	TIC	1501:1503	arg1	polypills					1480:1488	polypills	1480:1488	polypills of ASA and TIC	1480:1503	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	5	51	from	mixing	901:906	arg1	structures					957:966	each other's crystal structures	936:966	each other's crystal structures	936:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	3	52	theme	ASA	467:469	arg1	strategy					455:462	a preformulation strategy	438:462	a preformulation strategy of ASA	438:469	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	0	53	theme	Aspirin	59:65	arg1	usage					26:30	therapeutic usage	14:30	therapeutic usage of combined Ticagrelor and Aspirin	14:65	Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.
28652091	7	54	theme	liquid	1068:1073	arg1	appearance					1041:1050	The appearance	1037:1050	The appearance of the eutectic liquid	1037:1073	The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals.
28652091	9	55	theme	degradation	1385:1395	arg1	products					1397:1404	corresponding degradation products	1371:1404	corresponding degradation products	1371:1404	Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products.
28652091	5	56	theme	crystal	949:955	arg1	structures					957:966	each other's crystal structures	936:966	each other's crystal structures	936:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	5	57	theme	eutectic	793:800	arg1	transition					802:811	A simple eutectic transition	784:811	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457	784:873	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	11	58	theme	high	1590:1593	arg1	temperatures					1595:1606	high temperatures	1590:1606	high temperatures	1590:1606	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	8	59	theme	ASA	1237:1239	arg1	decomposition					1220:1232	prior decomposition	1214:1232	prior decomposition	1214:1232	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	8	60	theme	prior	1214:1218	arg1	decomposition					1220:1232	prior decomposition	1214:1232	prior decomposition	1214:1232	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	8	61	theme	TIC	1284:1286	arg1	sites					1300:1304	well-identified TIC interaction sites	1268:1304	well-identified TIC interaction sites	1268:1304	The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites.
28652091	3	62	theme	P2Y12-receptor	480:493	arg1	Ticagrelor					506:515	the P2Y12-receptor antagonist Ticagrelor	476:515	the P2Y12-receptor antagonist Ticagrelor (TIC)	476:521	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	3	62	theme	P2Y12-receptor	480:493	arg1	TIC					518:520	TIC	518:520	TIC	518:520	Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC).
28652091	1	63	theme	P2Y12-receptor	226:239	arg1	antagonist					241:250	a P2Y12-receptor antagonist	224:250	a P2Y12-receptor antagonist	224:250	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	4	64	dep	transform	720:728	arg1	infrared					730:737	infrared	730:737	transform infrared measurements and thermogravimetric analysis	720:781	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	10	65	theme	degradation	1426:1436	arg1	N-dealkylation					1449:1462	N-dealkylation	1449:1462	N-dealkylation	1449:1462	The most important degradation pathway is N-dealkylation.
28652091	10	65	theme	degradation	1426:1436	arg1	pathway					1438:1444	The most important degradation pathway	1407:1444	The most important degradation pathway	1407:1444	The most important degradation pathway is N-dealkylation.
28652091	2	66	theme	combination	320:330	arg1	polypill					343:350	polypill	343:350	polypill	343:350	To improve patient adherence to such treatments, combination therapies (polypill) are envisioned.
28652091	2	66	theme	combination	320:330	arg1	therapies					332:340	combination therapies	320:340	combination therapies (polypill)	320:351	To improve patient adherence to such treatments, combination therapies (polypill) are envisioned.
28652091	11	67	from	approach	1518:1525	arg1	conclusion					1468:1477	conclusion	1468:1477	conclusion	1468:1477	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	4	68	theme	mass	650:653	arg1	spectrometry					655:666	liquid chromatography-high resolution-multistage mass spectrometry	601:666	liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn)	601:678	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	4	68	theme	mass	650:653	arg1	LC-HR-MSn					669:677	LC-HR-MSn	669:677	LC-HR-MSn	669:677	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	0	69	theme	solid-state	75:85	arg1	studies					102:108	solid-state and analytical studies	75:108	solid-state and analytical studies	75:108	Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies.
28652091	4	70	theme	as	684:685	arg1	techniques					701:710	as complementary techniques	684:710	as complementary techniques	684:710	The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis.
28652091	5	71	from	molecules	923:931	arg1	structures					957:966	each other's crystal structures	936:966	each other's crystal structures	936:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	1	72	theme	acute	152:156	arg1	syndrome					167:174	acute coronary syndrome	152:174	acute coronary syndrome	152:174	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
28652091	11	73	theme	viable	1511:1516	arg1	polypills					1480:1488	polypills	1480:1488	polypills of ASA and TIC	1480:1503	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	11	73	theme	viable	1511:1516	arg1	approach					1518:1525	a viable approach	1509:1525	a viable approach	1509:1525	In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.
28652091	5	74	theme	mole	828:831	arg1	fraction					833:840	a mole fraction	826:840	a mole fraction for the eutectic liquid of 0.457	826:873	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	9	75	theme	interaction	1313:1323	arg1	products					1325:1332	Seven interaction products	1307:1332	Seven interaction products	1307:1332	Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products.
28652091	5	76	from	ASA	911:913	arg1	structures					957:966	each other's crystal structures	936:966	each other's crystal structures	936:966	A simple eutectic transition at 98°C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited.
28652091	1	77	theme	coronary	158:165	arg1	syndrome					167:174	acute coronary syndrome	152:174	acute coronary syndrome	152:174	The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA).
30335141	7	0	theme	suggestive	1217:1226	arg1	compartments					1203:1214	the TGN/post-Golgi compartments	1184:1214	the TGN/post-Golgi compartments	1184:1214	This correlated with alkalinization of the TGN/post-Golgi compartments, suggestive of a gain-of-function.
30335141	2	1	theme	exchanger	363:371	arg1	SLC9A7					378:383	the alkali cation/proton exchanger gene SLC9A7	338:383	the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7)	338:419	Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7).
30335141	1	2	theme	de	286:287	arg1	variant					303:309	a recurrent de novo missense variant	274:309	a recurrent de novo missense variant (c.1543C>T:p	274:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	10	3	theme	neurodevelopmental	1759:1776	arg1	deficits					1778:1785	neurodevelopmental deficits	1759:1785	neurodevelopmental deficits	1759:1785	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	1	4	theme	missense	294:301	arg1	variant					303:309	a recurrent de novo missense variant	274:309	a recurrent de novo missense variant (c.1543C>T:p	274:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	9	5	theme	patient	1420:1426	arg1	sera					1428:1431	patient sera	1420:1431	patient sera	1420:1431	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	3	6	from	Xp11.3	465:470	arg1	chromosome					451:460	human X chromosome	443:460	human X chromosome at Xp11.3	443:470	SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype.
30335141	3	7	theme	human	511:515	arg1	phenotype					517:525	a human phenotype	509:525	a human phenotype	509:525	SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype.
30335141	4	8	from	tissues	632:638	arg1	abundant					575:582	abundant	575:582	abundant	575:582	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	9	9	theme	abnormal	1450:1457	arg1	profile					1475:1481	an abnormal N-glycosylation profile	1447:1481	an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation	1447:1569	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	6	10	theme	Leu515Phe	831:839	arg1	protein					848:854	the Leu515Phe mutant protein	827:854	the Leu515Phe mutant protein	827:854	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	10	11	theme	X-linked	1840:1847	arg1	ID					1849:1850	X-linked ID	1840:1850	X-linked ID	1840:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	1	12	theme	nonsyndromic	215:226	arg1	disability					241:250	multigenerational nonsyndromic intellectual disability	197:250	multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p	197:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	1	12	theme	nonsyndromic	215:226	arg1	ID					253:254	ID	253:254	ID	253:254	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	6	13	theme	oligosaccharide	928:942	arg1	maturation					944:953	its N-linked oligosaccharide maturation	915:953	its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein,	915:1072	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	8	14	theme	Membrane	1251:1258	arg1	trafficking					1260:1270	Membrane trafficking	1251:1270	Membrane trafficking of glycosylation-deficient Leu515Phe	1251:1307	Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected.
30335141	4	15	from	muscle	603:608	arg1	abundant					575:582	abundant	575:582	abundant	575:582	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	4	16	theme	various	614:620	arg1	tissues					632:638	various secretory tissues	614:638	various secretory tissues	614:638	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	10	17	theme	pH	1655:1656	arg1	homeostasis					1658:1668	TGN/post-Golgi pH homeostasis	1640:1668	TGN/post-Golgi pH homeostasis	1640:1668	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	9	18	theme	sera	1428:1431	arg1	analysis					1408:1415	Mass spectrometry analysis	1390:1415	Mass spectrometry analysis of patient sera	1390:1431	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	8	19	theme	Leu515Phe	1299:1307	arg1	trafficking					1260:1270	Membrane trafficking	1251:1270	Membrane trafficking of glycosylation-deficient Leu515Phe	1251:1307	Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected.
30335141	8	19	theme	Leu515Phe	1299:1307	arg1	VSVG					1328:1331	co-transfected VSVG	1313:1331	co-transfected VSVG to the cell surface	1313:1351	Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected.
30335141	9	20	theme	diagnostic	1511:1520	arg1	marker					1522:1527	a clinical diagnostic marker	1500:1527	a clinical diagnostic marker for congenital disorders of glycosylation	1500:1569	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	9	20	theme	diagnostic	1511:1520	arg1	transferrin					1487:1497	transferrin	1487:1497	transferrin	1487:1497	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	6	21	theme	TGN/post-Golgi	886:899	arg1	vesicles					901:908	the TGN/post-Golgi vesicles	882:908	the TGN/post-Golgi vesicles	882:908	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	8	22	theme	co-transfected	1313:1326	arg1	VSVG					1328:1331	co-transfected VSVG	1313:1331	co-transfected VSVG to the cell surface	1313:1351	Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected.
30335141	6	23	theme	co-transfected	976:989	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	23	theme	co-transfected	976:989	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	1	24	dep	de	286:287	arg1	novo					289:292	novo	289:292	novo	289:292	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	4	25	from	brain	587:591	arg1	abundant					575:582	abundant	575:582	abundant	575:582	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	6	26	gly	glycoprotein	1060:1071	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	26	gly	glycoprotein	1060:1071	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	8	27	theme	cell	1340:1343	arg1	surface					1345:1351	the cell surface	1336:1351	the cell surface	1336:1351	Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected.
30335141	4	28	from	abundant	575:582	arg1	tissues					632:638	various secretory tissues	614:638	various secretory tissues	614:638	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	4	28	from	abundant	575:582	arg1	brain					587:591	brain	587:591	brain	587:591	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	4	28	from	abundant	575:582	arg1	muscle					603:608	skeletal muscle	594:608	skeletal muscle	594:608	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	1	29	theme	unrelated	173:181	arg1	families					183:190	two unrelated families	169:190	two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p	169:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	10	30	theme	particular	1808:1817	arg1	form					1832:1835	this particular nonsyndromic form	1803:1835	this particular nonsyndromic form of X-linked ID	1803:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	10	31	theme	exported	1691:1698	arg1	cargo					1700:1704	exported cargo	1691:1704	exported cargo	1691:1704	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	0	32	theme	Golgi	111:115	arg1	acidification					117:129	Golgi acidification	111:129	Golgi acidification	111:129	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	6	33	theme	G	1051:1051	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	33	theme	G	1051:1051	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	0	34	theme	intellectual	68:79	arg1	disability					81:90	nonsyndromic X-linked intellectual disability	46:90	nonsyndromic X-linked intellectual disability	46:90	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	10	35	theme	glycosylation	1674:1686	arg1	regulation					1626:1635	the regulation	1622:1635	the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID	1622:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	6	36	theme	stomatitis	1034:1043	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	36	theme	stomatitis	1034:1043	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	10	37	dep	pathophysiology	1739:1753	arg1	the					1726:1728	the	1726:1728	the	1726:1728	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	0	38	theme	missense	12:19	arg1	variant					21:27	A recurrent missense variant	0:27	A recurrent missense variant in SLC9A7	0:37	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	3	39	theme	human	443:447	arg1	chromosome					451:460	human X chromosome	443:460	human X chromosome at Xp11.3	443:470	SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype.
30335141	6	40	theme	membrane	1001:1008	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	40	theme	membrane	1001:1008	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	0	41	theme	X-linked	59:66	arg1	disability					81:90	nonsyndromic X-linked intellectual disability	46:90	nonsyndromic X-linked intellectual disability	46:90	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	2	42	theme	cation/proton	349:361	arg1	SLC9A7					378:383	the alkali cation/proton exchanger gene SLC9A7	338:383	the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7)	338:419	Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7).
30335141	1	43	dep	c.1543C>T	312:320	arg1	p					322:322	p	322:322	c.1543C>T:p	312:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	6	44	theme	ovary	809:813	arg1	cells					820:824	transfected Chinese hamster ovary AP-1 cells	781:824	transfected Chinese hamster ovary AP-1 cells	781:824	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	9	45	theme	Mass	1390:1393	arg1	analysis					1408:1415	Mass spectrometry analysis	1390:1415	Mass spectrometry analysis of patient sera	1390:1431	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	6	46	theme	Chinese	793:799	arg1	cells					820:824	transfected Chinese hamster ovary AP-1 cells	781:824	transfected Chinese hamster ovary AP-1 cells	781:824	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	10	47	theme	cargo	1700:1704	arg1	glycosylation					1674:1686	glycosylation	1674:1686	glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID	1674:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	10	47	theme	cargo	1700:1704	arg1	homeostasis					1658:1668	TGN/post-Golgi pH homeostasis	1640:1668	TGN/post-Golgi pH homeostasis	1640:1668	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	7	48	theme	gain-of-function	1233:1248	arg1	suggestive					1217:1226	suggestive	1217:1226	suggestive	1217:1226	This correlated with alkalinization of the TGN/post-Golgi compartments, suggestive of a gain-of-function.
30335141	2	49	theme	gene	373:376	arg1	SLC9A7					378:383	the alkali cation/proton exchanger gene SLC9A7	338:383	the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7)	338:419	Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7).
30335141	1	50	theme	recurrent	276:284	arg1	variant					303:309	a recurrent de novo missense variant	274:309	a recurrent de novo missense variant (c.1543C>T:p	274:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	6	51	theme	VSVG	1054:1057	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	51	theme	VSVG	1054:1057	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	10	52	theme	nonsyndromic	1819:1830	arg1	form					1832:1835	this particular nonsyndromic form	1803:1835	this particular nonsyndromic form of X-linked ID	1803:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	10	53	theme	crucial	1595:1601	arg1	role					1603:1606	a crucial role	1593:1606	a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID	1593:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	9	54	theme	N-glycosylation	1459:1473	arg1	profile					1475:1481	an abnormal N-glycosylation profile	1447:1481	an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation	1447:1569	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	6	55	theme	mutant	841:846	arg1	protein					848:854	the Leu515Phe mutant protein	827:854	the Leu515Phe mutant protein	827:854	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	4	56	theme	secretory	622:630	arg1	tissues					632:638	various secretory tissues	614:638	various secretory tissues	614:638	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	7	57	theme	TGN/post-Golgi	1188:1201	arg1	compartments					1203:1214	the TGN/post-Golgi compartments	1184:1214	the TGN/post-Golgi compartments	1184:1214	This correlated with alkalinization of the TGN/post-Golgi compartments, suggestive of a gain-of-function.
30335141	10	58	theme	ID	1849:1850	arg1	form					1832:1835	this particular nonsyndromic form	1803:1835	this particular nonsyndromic form of X-linked ID	1803:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	1	59	theme	multigenerational	197:213	arg1	disability					241:250	multigenerational nonsyndromic intellectual disability	197:250	multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p	197:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	1	59	theme	multigenerational	197:213	arg1	ID					253:254	ID	253:254	ID	253:254	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	6	60	theme	SLC9A7	1118:1123	arg1	wild-type					1125:1133	SLC9A7 wild-type	1118:1133	SLC9A7 wild-type	1118:1133	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	0	61	theme	aberrant	135:142	arg1	glycosylation					144:156	aberrant glycosylation	135:156	aberrant glycosylation	135:156	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	1	62	theme	intellectual	228:239	arg1	disability					241:250	multigenerational nonsyndromic intellectual disability	197:250	multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p	197:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	1	62	theme	intellectual	228:239	arg1	ID					253:254	ID	253:254	ID	253:254	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	6	63	theme	N-linked	919:926	arg1	maturation					944:953	its N-linked oligosaccharide maturation	915:953	its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein,	915:1072	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	9	64	theme	glycosylation	1557:1569	arg1	disorders					1544:1552	congenital disorders	1533:1552	congenital disorders of glycosylation	1533:1569	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	4	65	theme	skeletal	594:601	arg1	muscle					603:608	skeletal muscle	594:608	skeletal muscle	594:608	The gene is widely transcribed, but especially abundant in brain, skeletal muscle and various secretory tissues.
30335141	10	66	theme	homeostasis	1658:1668	arg1	regulation					1626:1635	the regulation	1622:1635	the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID	1622:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	10	67	theme	cellular	1730:1737	arg1	pathophysiology					1739:1753	cellular pathophysiology	1730:1753	cellular pathophysiology	1730:1753	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	5	68	theme	Golgi	677:681	arg1	apparatus					683:691	the Golgi apparatus	673:691	the Golgi apparatus	673:691	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
30335141	5	69	from	enrichment	709:718	arg1	vesicles					768:775	post-Golgi vesicles	757:775	post-Golgi vesicles	757:775	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
30335141	5	69	from	enrichment	709:718	arg1	TGN					748:750	TGN	748:750	TGN	748:750	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
30335141	5	69	from	enrichment	709:718	arg1	network					739:745	the trans-Golgi network	723:745	the trans-Golgi network (TGN)	723:751	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
30335141	6	70	link	N-linked	919:926	arg1	maturation					944:953	its N-linked oligosaccharide maturation	915:953	its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein,	915:1072	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	10	71	theme	TGN/post-Golgi	1640:1653	arg1	homeostasis					1658:1668	TGN/post-Golgi pH homeostasis	1640:1668	TGN/post-Golgi pH homeostasis	1640:1668	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	9	72	theme	clinical	1502:1509	arg1	marker					1522:1527	a clinical diagnostic marker	1500:1527	a clinical diagnostic marker for congenital disorders of glycosylation	1500:1569	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	9	72	theme	clinical	1502:1509	arg1	transferrin					1487:1497	transferrin	1487:1497	transferrin	1487:1497	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	8	73	theme	glycosylation-deficient	1275:1297	arg1	Leu515Phe					1299:1307	glycosylation-deficient Leu515Phe	1275:1307	glycosylation-deficient Leu515Phe	1275:1307	Membrane trafficking of glycosylation-deficient Leu515Phe and co-transfected VSVG to the cell surface, however, was relatively unaffected.
30335141	10	74	link	X-linked	1840:1847	arg1	ID					1849:1850	X-linked ID	1840:1850	X-linked ID	1840:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	6	75	theme	secretory	991:999	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	75	theme	secretory	991:999	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	2	76	dep	Leu515Phe	324:332	arg1	SLC9A7					378:383	the alkali cation/proton exchanger gene SLC9A7	338:383	the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7)	338:419	Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7).
30335141	7	77	theme	compartments	1203:1214	arg1	alkalinization					1166:1179	alkalinization	1166:1179	alkalinization of the TGN/post-Golgi compartments, suggestive of a gain-of-function	1166:1248	This correlated with alkalinization of the TGN/post-Golgi compartments, suggestive of a gain-of-function.
30335141	10	78	gly	glycosylation	1674:1686	arg1	cargo					1700:1704	exported cargo	1691:1704	exported cargo	1691:1704	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	9	79	theme	congenital	1533:1542	arg1	disorders					1544:1552	congenital disorders	1533:1552	congenital disorders of glycosylation	1533:1569	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	0	80	from	variant	21:27	arg1	SLC9A7					32:37	SLC9A7	32:37	SLC9A7	32:37	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	5	81	theme	trans-Golgi	727:737	arg1	TGN					748:750	TGN	748:750	TGN	748:750	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
30335141	5	81	theme	trans-Golgi	727:737	arg1	network					739:745	the trans-Golgi network	723:745	the trans-Golgi network (TGN)	723:751	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
30335141	1	82	dep	variant	303:309	arg1	c.1543C>T					312:320	c.1543C>T	312:320	c.1543C>T:p	312:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	0	83	theme	acidification	117:129	arg1	alteration					97:106	alteration	97:106	alteration of Golgi acidification and aberrant glycosylation	97:156	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	2	84	dep	SLC9A7	378:383	arg1	referred					400:407	referred	400:407	commonly referred to as NHE7	391:418	Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7).
30335141	5	85	theme	prominent	699:707	arg1	enrichment					709:718	prominent enrichment	699:718	prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles	699:775	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
30335141	0	86	theme	recurrent	2:10	arg1	variant					21:27	A recurrent missense variant	0:27	A recurrent missense variant in SLC9A7	0:37	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	3	87	located	located	432:438	arg2	SLC9A7					422:427	SLC9A7	422:427	SLC9A7	422:427	SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype.
30335141	3	87	located	located	432:438	arg1	chromosome					451:460	human X chromosome	443:460	human X chromosome at Xp11.3	443:470	SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype.
30335141	6	88	theme	virus	1045:1049	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	88	theme	virus	1045:1049	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	10	89	from	role	1603:1606	arg1	regulation					1626:1635	the regulation	1622:1635	the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID	1622:1850	These data implicate a crucial role for SLC9A7 in the regulation of TGN/post-Golgi pH homeostasis and glycosylation of exported cargo, which may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked ID.
30335141	6	90	theme	vesicular	1024:1032	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	90	theme	vesicular	1024:1032	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	91	gly	glycoprotein	1010:1021	arg1	glycoprotein					1060:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	vesicular stomatitis virus G (VSVG) glycoprotein	1024:1071	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	6	91	gly	glycoprotein	1010:1021	arg1	glycoprotein					1010:1021	a co-transfected secretory membrane glycoprotein	974:1021	a co-transfected secretory membrane glycoprotein	974:1021	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	3	92	theme	X	449:449	arg1	chromosome					451:460	human X chromosome	443:460	human X chromosome at Xp11.3	443:470	SLC9A7 is located on human X chromosome at Xp11.3 and has not yet been associated with a human phenotype.
30335141	0	93	theme	nonsyndromic	46:57	arg1	disability					81:90	nonsyndromic X-linked intellectual disability	46:90	nonsyndromic X-linked intellectual disability	46:90	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	6	94	theme	AP-1	815:818	arg1	cells					820:824	transfected Chinese hamster ovary AP-1 cells	781:824	transfected Chinese hamster ovary AP-1 cells	781:824	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	0	95	theme	glycosylation	144:156	arg1	alteration					97:106	alteration	97:106	alteration of Golgi acidification and aberrant glycosylation	97:156	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	2	96	theme	alkali	342:347	arg1	SLC9A7					378:383	the alkali cation/proton exchanger gene SLC9A7	338:383	the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7)	338:419	Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7).
30335141	1	97	with	families	183:190	arg1	disability					241:250	multigenerational nonsyndromic intellectual disability	197:250	multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p	197:322	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	1	97	with	families	183:190	arg1	ID					253:254	ID	253:254	ID	253:254	We report two unrelated families with multigenerational nonsyndromic intellectual disability (ID) segregating with a recurrent de novo missense variant (c.1543C>T:p.
30335141	6	98	theme	hamster	801:807	arg1	cells					820:824	transfected Chinese hamster ovary AP-1 cells	781:824	transfected Chinese hamster ovary AP-1 cells	781:824	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	0	99	link	X-linked	59:66	arg1	disability					81:90	nonsyndromic X-linked intellectual disability	46:90	nonsyndromic X-linked intellectual disability	46:90	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
30335141	9	100	theme	spectrometry	1395:1406	arg1	analysis					1408:1415	Mass spectrometry analysis	1390:1415	Mass spectrometry analysis of patient sera	1390:1431	Mass spectrometry analysis of patient sera also revealed an abnormal N-glycosylation profile for transferrin, a clinical diagnostic marker for congenital disorders of glycosylation.
30335141	6	101	theme	transfected	781:791	arg1	cells					820:824	transfected Chinese hamster ovary AP-1 cells	781:824	transfected Chinese hamster ovary AP-1 cells	781:824	In transfected Chinese hamster ovary AP-1 cells, the Leu515Phe mutant protein was correctly targeted to the TGN/post-Golgi vesicles, but its N-linked oligosaccharide maturation as well as that of a co-transfected secretory membrane glycoprotein, vesicular stomatitis virus G (VSVG) glycoprotein, was reduced compared to cells co-expressing SLC9A7 wild-type and VSVG.
30335141	2	102	dep	referred	400:407	arg1	also					386:389	also	386:389	also	386:389	Leu515Phe) in the alkali cation/proton exchanger gene SLC9A7 (also commonly referred to as NHE7).
30335141	5	103	theme	post-Golgi	757:766	arg1	vesicles					768:775	post-Golgi vesicles	757:775	post-Golgi vesicles	757:775	Within cells, SLC9A7 resides in the Golgi apparatus, with prominent enrichment in the trans-Golgi network (TGN) and post-Golgi vesicles.
29339807	0	0	theme	castration-resistant	67:86	arg1	cells					104:108	castration-resistant prostate cancer cells	67:108	castration-resistant prostate cancer cells	67:108	Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells.
29339807	2	1	theme	cancer	468:473	arg1	development					433:443	the development	429:443	the development of aggressive prostate cancer	429:473	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	1	2	from	modifications	165:177	arg1	proteins					182:189	proteins	182:189	proteins	182:189	Glycosylation is recognized as one of the most common modifications on proteins.
29339807	3	3	from	expression	520:529	arg1	cells					598:602	different prostate cancer cells	572:602	different prostate cancer cells	572:602	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	2	4	theme	prostate	459:466	arg1	cancer					468:473	aggressive prostate cancer	448:473	aggressive prostate cancer	448:473	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	4	5	theme	LAPC4	897:901	arg1	cells					903:907	androgen-dependent and androgen-resistant LAPC4 cells	855:907	androgen-dependent and androgen-resistant LAPC4 cells	855:907	In this study, using a proteomics approach, we analyzed androgen-dependent and androgen-resistant LAPC4 cells and identified FUT8 to be significantly overexpressed in the androgen-resistant LAPC4 cells.
29339807	5	6	theme	in	1138:1139	arg1	models					1172:1177	the in vivo castrated tumor xenograft models	1134:1177	the in vivo castrated tumor xenograft models	1134:1177	These findings were independently confirmed in LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
29339807	0	7	theme	cancer	97:102	arg1	cells					104:108	castration-resistant prostate cancer cells	67:108	castration-resistant prostate cancer cells	67:108	Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells.
29339807	7	8	theme	enzyme	1411:1416	arg1	role					1391:1394	the functional role	1376:1394	the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer	1376:1475	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	6	9	theme	PSA	1279:1281	arg1	expression					1283:1292	the decreased PSA expression	1265:1292	the decreased PSA expression in prostate cancer specimens	1265:1321	Similarly, we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens.
29339807	7	10	theme	prostate	1461:1468	arg1	cancer					1470:1475	castration-resistant prostate cancer	1440:1475	castration-resistant prostate cancer	1440:1475	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	0	11	theme	prostate	88:95	arg1	cells					104:108	castration-resistant prostate cancer cells	67:108	castration-resistant prostate cancer cells	67:108	Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells.
29339807	6	12	theme	FUT8	1235:1238	arg1	overexpression					1217:1230	overexpression	1217:1230	overexpression of FUT8	1217:1238	Similarly, we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens.
29339807	3	13	theme	FUT8	534:537	arg1	expression					520:529	the abnormal expression	507:529	the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells	507:602	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	7	14	from	role	1391:1394	arg1	development					1425:1435	the development	1421:1435	the development of castration-resistant prostate cancer	1421:1475	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	7	15	theme	cancer	1470:1475	arg1	development					1425:1435	the development	1421:1435	the development of castration-resistant prostate cancer	1421:1475	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	0	16	from	fucosyltransferase	26:43	arg1	development					52:62	the development	48:62	the development of castration-resistant prostate cancer cells	48:108	Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells.
29339807	3	17	from	androgen-dependent	739:756	arg1	progression					722:732	prostate cancer progression	706:732	prostate cancer progression from androgen-dependent to castration-resistant prostate cancer	706:796	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	7	18	theme	first	1354:1358	arg1	this					1342:1345	this	1342:1345	this	1342:1345	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	7	18	theme	first	1354:1358	arg1	study					1360:1364	the first study	1350:1364	the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer	1350:1475	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	2	19	theme	fucosyltransferase	254:271	arg1	expression					232:241	aberrant expression	223:241	aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins,	223:380	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	1	20	theme	common	158:163	arg1	modifications					165:177	the most common modifications	149:177	the most common modifications on proteins	149:189	Glycosylation is recognized as one of the most common modifications on proteins.
29339807	0	21	theme	cells	104:108	arg1	development					52:62	the development	48:62	the development of castration-resistant prostate cancer cells	48:108	Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells.
29339807	3	22	theme	prostate	706:713	arg1	progression					722:732	prostate cancer progression	706:732	prostate cancer progression from androgen-dependent to castration-resistant prostate cancer	706:796	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	2	23	gly	glycoproteins	367:379	arg1	glycoproteins					367:379	the N-linked glycoproteins	354:379	the N-linked glycoproteins	354:379	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	5	24	theme	castrated	1146:1154	arg1	models					1172:1177	the in vivo castrated tumor xenograft models	1134:1177	the in vivo castrated tumor xenograft models	1134:1177	These findings were independently confirmed in LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
29339807	1	25	theme	modifications	165:177	arg1	Glycosylation					111:123	Glycosylation	111:123	Glycosylation	111:123	Glycosylation is recognized as one of the most common modifications on proteins.
29339807	1	25	theme	modifications	165:177	arg1	modifications					165:177	the most common modifications	149:177	the most common modifications on proteins	149:189	Glycosylation is recognized as one of the most common modifications on proteins.
29339807	1	25	theme	modifications	165:177	arg1	one					142:144	one	142:144	one	142:144	Glycosylation is recognized as one of the most common modifications on proteins.
29339807	3	26	theme	cancer	715:720	arg1	progression					722:732	prostate cancer progression	706:732	prostate cancer progression from androgen-dependent to castration-resistant prostate cancer	706:796	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	4	27	theme	androgen-resistant	878:895	arg1	cells					903:907	androgen-dependent and androgen-resistant LAPC4 cells	855:907	androgen-dependent and androgen-resistant LAPC4 cells	855:907	In this study, using a proteomics approach, we analyzed androgen-dependent and androgen-resistant LAPC4 cells and identified FUT8 to be significantly overexpressed in the androgen-resistant LAPC4 cells.
29339807	3	28	theme	fucosylation	556:567	arg1	expression					520:529	the abnormal expression	507:529	the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells	507:602	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	3	29	theme	abnormal	511:518	arg1	expression					520:529	the abnormal expression	507:529	the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells	507:602	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	7	30	gly	fucosylated	1399:1409	arg1	enzyme					1411:1416	fucosylated enzyme	1399:1416	fucosylated enzyme	1399:1416	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	3	31	theme	castration-resistant	761:780	arg1	cancer					791:796	castration-resistant prostate cancer	761:796	castration-resistant prostate cancer	761:796	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	6	32	theme	prostate	1297:1304	arg1	specimens					1313:1321	prostate cancer specimens	1297:1321	prostate cancer specimens	1297:1321	Similarly, we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens.
29339807	4	33	theme	androgen-dependent	855:872	arg1	cells					903:907	androgen-dependent and androgen-resistant LAPC4 cells	855:907	androgen-dependent and androgen-resistant LAPC4 cells	855:907	In this study, using a proteomics approach, we analyzed androgen-dependent and androgen-resistant LAPC4 cells and identified FUT8 to be significantly overexpressed in the androgen-resistant LAPC4 cells.
29339807	6	34	theme	cancer	1306:1311	arg1	specimens					1313:1321	prostate cancer specimens	1297:1321	prostate cancer specimens	1297:1321	Similarly, we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens.
29339807	3	35	theme	prostate	782:789	arg1	cancer					791:796	castration-resistant prostate cancer	761:796	castration-resistant prostate cancer	761:796	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	6	36	theme	decreased	1269:1277	arg1	expression					1283:1292	the decreased PSA expression	1265:1292	the decreased PSA expression in prostate cancer specimens	1265:1321	Similarly, we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens.
29339807	7	37	theme	castration-resistant	1440:1459	arg1	cancer					1470:1475	castration-resistant prostate cancer	1440:1475	castration-resistant prostate cancer	1440:1475	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	0	38	theme	α	18:18	arg1	Overexpression					0:13	Overexpression	0:13	Overexpression of α (1,6)	0:24	Overexpression of α (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells.
29339807	2	39	dep	core-GlcNAc	339:349	arg1	GDP-fucose					325:334	GDP-fucose	325:334	GDP-fucose	325:334	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	3	40	theme	glycoprotein	543:554	arg1	fucosylation					556:567	glycoprotein fucosylation	543:567	glycoprotein fucosylation	543:567	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	2	41	theme	cellular	392:399	arg1	behavior					401:408	cellular behavior	392:408	cellular behavior that could lead to the development of aggressive prostate cancer	392:473	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	2	42	theme	aggressive	448:457	arg1	cancer					468:473	aggressive prostate cancer	448:473	aggressive prostate cancer	448:473	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	4	43	theme	androgen-resistant	970:987	arg1	cells					995:999	the androgen-resistant LAPC4 cells	966:999	the androgen-resistant LAPC4 cells	966:999	In this study, using a proteomics approach, we analyzed androgen-dependent and androgen-resistant LAPC4 cells and identified FUT8 to be significantly overexpressed in the androgen-resistant LAPC4 cells.
29339807	3	44	theme	cancer	591:596	arg1	cells					598:602	different prostate cancer cells	572:602	different prostate cancer cells	572:602	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	6	45	from	expression	1283:1292	arg1	specimens					1313:1321	prostate cancer specimens	1297:1321	prostate cancer specimens	1297:1321	Similarly, we also demonstrated that overexpression of FUT8 might be responsible for the decreased PSA expression in prostate cancer specimens.
29339807	2	46	theme	glycoproteins	367:379	arg1	core-GlcNAc					339:349	core-GlcNAc	339:349	core-GlcNAc of the N-linked glycoproteins	339:379	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	2	47	theme	aberrant	223:230	arg1	expression					232:241	aberrant expression	223:241	aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins,	223:380	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	2	48	link	N-linked	358:365	arg1	glycoproteins					367:379	the N-linked glycoproteins	354:379	the N-linked glycoproteins	354:379	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	3	49	theme	different	572:580	arg1	cells					598:602	different prostate cancer cells	572:602	different prostate cancer cells	572:602	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	5	50	theme	tumor	1156:1160	arg1	models					1172:1177	the in vivo castrated tumor xenograft models	1134:1177	the in vivo castrated tumor xenograft models	1134:1177	These findings were independently confirmed in LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
29339807	2	51	theme	fucose	313:318	arg1	transfer					301:308	the transfer	297:308	the transfer of fucose	297:318	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	5	52	theme	xenograft	1162:1170	arg1	models					1172:1177	the in vivo castrated tumor xenograft models	1134:1177	the in vivo castrated tumor xenograft models	1134:1177	These findings were independently confirmed in LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
29339807	3	53	theme	dysregulated	659:670	arg1	fucosylation					672:683	dysregulated fucosylation	659:683	dysregulated fucosylation	659:683	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	3	54	theme	prostate	582:589	arg1	cells					598:602	different prostate cancer cells	572:602	different prostate cancer cells	572:602	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	7	55	theme	functional	1380:1389	arg1	role					1391:1394	the functional role	1376:1394	the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer	1376:1475	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	7	56	theme	fucosylated	1399:1409	arg1	enzyme					1411:1416	fucosylated enzyme	1399:1416	fucosylated enzyme	1399:1416	To our knowledge, this is the first study reporting the functional role of fucosylated enzyme in the development of castration-resistant prostate cancer.
29339807	2	57	theme	1,6	249:251	arg1	FUT8					274:277	FUT8	274:277	FUT8	274:277	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	2	57	theme	1,6	249:251	arg1	fucosyltransferase					254:271	α (1,6) fucosyltransferase	246:271	α (1,6) fucosyltransferase (FUT8)	246:278	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	4	58	theme	proteomics	822:831	arg1	approach					833:840	a proteomics approach	820:840	a proteomics approach	820:840	In this study, using a proteomics approach, we analyzed androgen-dependent and androgen-resistant LAPC4 cells and identified FUT8 to be significantly overexpressed in the androgen-resistant LAPC4 cells.
29339807	3	59	gly	glycoprotein	543:554	arg1	glycoprotein					543:554	glycoprotein fucosylation	543:567	glycoprotein fucosylation	543:567	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	3	60	gly	fucosylation	672:683	arg1	progression					722:732	prostate cancer progression	706:732	prostate cancer progression from androgen-dependent to castration-resistant prostate cancer	706:796	While the relationship between the abnormal expression of FUT8 and glycoprotein fucosylation in different prostate cancer cells has been demonstrated, there is no evidence that shows dysregulated fucosylation might be involved in prostate cancer progression from androgen-dependent to castration-resistant prostate cancer.
29339807	2	61	theme	Recent	192:197	arg1	studies					199:205	Recent studies	192:205	Recent studies	192:205	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	5	62	theme	LAPC4	1049:1053	arg1	cells					1055:1059	LAPC4 cells	1049:1059	LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models	1049:1177	These findings were independently confirmed in LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
29339807	5	63	dep	in	1138:1139	arg1	vivo					1141:1144	vivo	1141:1144	vivo	1141:1144	These findings were independently confirmed in LAPC4 cells that were treated with non-steroidal anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
29339807	2	64	theme	α	246:246	arg1	FUT8					274:277	FUT8	274:277	FUT8	274:277	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	2	64	theme	α	246:246	arg1	fucosyltransferase					254:271	α (1,6) fucosyltransferase	246:271	α (1,6) fucosyltransferase (FUT8)	246:278	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	2	65	theme	N-linked	358:365	arg1	glycoproteins					367:379	the N-linked glycoproteins	354:379	the N-linked glycoproteins	354:379	Recent studies have shown that aberrant expression of α (1,6) fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that could lead to the development of aggressive prostate cancer.
29339807	4	66	theme	LAPC4	989:993	arg1	cells					995:999	the androgen-resistant LAPC4 cells	966:999	the androgen-resistant LAPC4 cells	966:999	In this study, using a proteomics approach, we analyzed androgen-dependent and androgen-resistant LAPC4 cells and identified FUT8 to be significantly overexpressed in the androgen-resistant LAPC4 cells.
28637198	6	0	theme	multitarget	1055:1065	arg1	supplement					1079:1088	potential multitarget active drug supplement	1045:1088	potential multitarget active drug supplement	1045:1088	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	3	1	theme	inhibitors	668:677	arg1	class					653:657	a promising class	641:657	a promising class of HIV-1 inhibitors	641:677	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	1	theme	inhibitors	668:677	arg1	triterpenes					624:634	pentacyclic triterpenes	612:634	pentacyclic triterpenes	612:634	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	1	theme	inhibitors	668:677	arg1	compounds					593:601	many natural compounds	580:601	many natural compounds	580:601	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	2	2	theme	HIV-1	352:356	arg1	RT					381:382	RT	381:382	RT	381:382	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	2	2	theme	HIV-1	352:356	arg1	transcriptase					366:378	the HIV-1 reverse transcriptase	348:378	the HIV-1 reverse transcriptase (RT)	348:383	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	8	3	theme	numerous	1324:1331	arg1	metabolites					1340:1350	its numerous active metabolites	1320:1350	its numerous active metabolites	1320:1350	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	1	4	theme	new	279:281	arg1	drugs					283:287	new drugs	279:287	new drugs against underexplored HIV-1 targets	279:323	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28637198	5	5	theme	Lupeol	845:850	arg1	studies					834:840	combination studies	822:840	combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations	822:928	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	8	6	theme	RT-associated	1397:1409	arg1	H					1417:1417	the RT-associated RNase H	1393:1417	the RT-associated RNase H function	1393:1426	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	3	7	theme	many	580:583	arg1	class					653:657	a promising class	641:657	a promising class of HIV-1 inhibitors	641:677	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	7	theme	many	580:583	arg1	triterpenes					624:634	pentacyclic triterpenes	612:634	pentacyclic triterpenes	612:634	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	7	theme	many	580:583	arg1	compounds					593:601	many natural compounds	580:601	many natural compounds	580:601	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	8	8	theme	H	1417:1417	arg1	function					1419:1426	the RT-associated RNase H function	1393:1426	the RT-associated RNase H function	1393:1426	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	3	9	theme	pentacyclic	612:622	arg1	triterpenes					624:634	pentacyclic triterpenes	612:634	pentacyclic triterpenes	612:634	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	6	10	theme	Ayurveda	1162:1169	arg1	plant					1181:1185	an Ayurveda medicinal plant	1159:1185	an Ayurveda medicinal plant containing Lupeol	1159:1203	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	6	10	theme	Ayurveda	1162:1169	arg1	indicus					1150:1156	Hemidesmus indicus	1139:1156	Hemidesmus indicus	1139:1156	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	0	11	theme	HIV-1	73:77	arg1	targets					84:90	innovative HIV-1 drug targets	62:90	innovative HIV-1 drug targets	62:90	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	5	12	theme	site	867:870	arg1	inhibitor					880:888	the active site RNase H inhibitor RDS1759	856:896	the active site RNase H inhibitor RDS1759	856:896	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	1	13	theme	several	167:173	arg1	anti-retrovirals					175:190	several anti-retrovirals	167:190	several anti-retrovirals	167:190	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28637198	8	14	theme	HIV-1	1442:1446	arg1	polymerase					1480:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase	1438:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase activity	1438:1498	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	2	15	theme	N-linked	500:507	arg1	glycoproteins					509:521	N-linked glycoproteins	500:521	N-linked glycoproteins	500:521	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	8	16	theme	RNA-dependent	1462:1474	arg1	polymerase					1480:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase	1438:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase activity	1438:1498	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	2	17	theme	ribonuclease	396:407	arg1	H					409:409	ribonuclease H	396:409	the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function	348:428	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	2	17	theme	ribonuclease	396:407	arg1	H					418:418	RNase H	412:418	RNase H	412:418	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	0	18	theme	Lupeol	116:121	arg1	mode					123:126	Lupeol mode	116:126	Lupeol mode of action	116:136	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	8	19	from	fact	1301:1304	arg1	able					1368:1371	able	1368:1371	able	1368:1371	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	8	20	theme	polymerase	1480:1489	arg1	activity					1491:1498	the HIV-1 RT-associated RNA-dependent DNA polymerase activity	1438:1498	the HIV-1 RT-associated RNA-dependent DNA polymerase activity	1438:1498	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	4	21	theme	triterpene	718:727	arg1	Lupeol					729:734	the pentacyclic triterpene Lupeol	702:734	the pentacyclic triterpene Lupeol	702:734	Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function.
28637198	0	22	theme	Multi-target	0:11	arg1	activity					13:20	Multi-target activity	0:20	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.	0:137	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	5	23	theme	docking	909:915	arg1	calculations					917:928	blind docking calculations	903:928	blind docking calculations	903:928	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	6	24	theme	results	1019:1025	arg1	searching					1031:1039	searching	1031:1039	searching for potential multitarget active drug supplement	1031:1088	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	6	24	theme	results	1019:1025	arg1	bases					1004:1008	the bases	1000:1008	the bases of these results	1000:1025	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	8	25	dep	H.	1353:1354	arg1	indicus					1356:1362	H. indicus	1353:1362	H. indicus	1353:1362	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	8	26	theme	metabolites	1340:1350	arg1	virtue					1310:1315	virtue	1310:1315	virtue of its numerous active metabolites	1310:1350	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	1	27	theme	underexplored	297:309	arg1	targets					317:323	underexplored HIV-1 targets	297:323	underexplored HIV-1 targets	297:323	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28637198	7	28	theme	drug	1285:1288	arg1	source					1290:1295	a valuable multitarget active drug source	1255:1295	a valuable multitarget active drug source	1255:1295	Results supported the potential of this plant as a valuable multitarget active drug source.
28637198	8	29	theme	cellular	1508:1515	arg1	α-glucosidase					1517:1529	the cellular α-glucosidase	1504:1529	the cellular α-glucosidase	1504:1529	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	7	30	theme	multitarget	1266:1276	arg1	source					1290:1295	a valuable multitarget active drug source	1255:1295	a valuable multitarget active drug source	1255:1295	Results supported the potential of this plant as a valuable multitarget active drug source.
28637198	3	31	theme	HIV-1	662:666	arg1	inhibitors					668:677	HIV-1 inhibitors	662:677	HIV-1 inhibitors	662:677	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	4	32	theme	HIV-1	766:770	arg1	function					794:801	the HIV-1 RT-associated RNase H function	762:801	the HIV-1 RT-associated RNase H function	762:801	Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function.
28637198	7	33	theme	plant	1246:1250	arg1	potential					1228:1236	the potential	1224:1236	the potential of this plant as a valuable multitarget active drug source	1224:1295	Results supported the potential of this plant as a valuable multitarget active drug source.
28637198	4	34	theme	RNase	786:790	arg1	function					794:801	the HIV-1 RT-associated RNase H function	762:801	the HIV-1 RT-associated RNase H function	762:801	Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function.
28637198	1	35	theme	novel	238:242	arg1	strategies					256:265	novel therapeutic strategies	238:265	novel therapeutic strategies	238:265	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28637198	5	36	theme	RT	975:976	arg1	pocket					989:994	an HIV-1 RT allosteric pocket	966:994	an HIV-1 RT allosteric pocket	966:994	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	6	37	theme	active	1067:1072	arg1	supplement					1079:1088	potential multitarget active drug supplement	1045:1088	potential multitarget active drug supplement	1045:1088	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	2	38	theme	reverse	358:364	arg1	RT					381:382	RT	381:382	RT	381:382	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	2	38	theme	reverse	358:364	arg1	transcriptase					366:378	the HIV-1 reverse transcriptase	348:378	the HIV-1 reverse transcriptase (RT)	348:383	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	6	39	theme	potential	1045:1053	arg1	supplement					1079:1088	potential multitarget active drug supplement	1045:1088	potential multitarget active drug supplement	1045:1088	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	6	40	theme	indicus	1150:1156	arg1	activity					1127:1134	the anti-HIV-1 activity	1112:1134	the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol	1112:1203	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	1	41	theme	anti-retrovirals	175:190	arg1	availability					151:162	the availability	147:162	the availability of several anti-retrovirals	147:190	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28637198	6	42	theme	anti-HIV-1	1116:1125	arg1	activity					1127:1134	the anti-HIV-1 activity	1112:1134	the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol	1112:1203	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	0	43	theme	action	131:136	arg1	mode					123:126	Lupeol mode	116:126	Lupeol mode of action	116:136	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	2	44	theme	endoplasmic	540:550	arg1	reticulum					552:560	the endoplasmic reticulum	536:560	the endoplasmic reticulum	536:560	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	5	45	theme	H	878:878	arg1	inhibitor					880:888	the active site RNase H inhibitor RDS1759	856:896	the active site RNase H inhibitor RDS1759	856:896	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	3	46	theme	natural	585:591	arg1	class					653:657	a promising class	641:657	a promising class of HIV-1 inhibitors	641:677	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	46	theme	natural	585:591	arg1	triterpenes					624:634	pentacyclic triterpenes	612:634	pentacyclic triterpenes	612:634	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	46	theme	natural	585:591	arg1	compounds					593:601	many natural compounds	580:601	many natural compounds	580:601	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	8	47	from	able	1368:1371	arg1	fact					1301:1304	fact	1301:1304	fact	1301:1304	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	5	48	theme	combination	822:832	arg1	studies					834:840	combination studies	822:840	combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations	822:928	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	8	49	theme	RNase	1411:1415	arg1	H					1417:1417	the RT-associated RNase H	1393:1417	the RT-associated RNase H function	1393:1426	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	5	50	theme	inhibitor	880:888	arg1	studies					834:840	combination studies	822:840	combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations	822:928	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	2	51	from	formation	523:531	arg1	reticulum					552:560	the endoplasmic reticulum	536:560	the endoplasmic reticulum	536:560	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	6	52	theme	medicinal	1171:1179	arg1	plant					1181:1185	an Ayurveda medicinal plant	1159:1185	an Ayurveda medicinal plant containing Lupeol	1159:1203	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	6	52	theme	medicinal	1171:1179	arg1	indicus					1150:1156	Hemidesmus indicus	1139:1156	Hemidesmus indicus	1139:1156	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	2	53	link	N-linked	500:507	arg1	glycoproteins					509:521	N-linked glycoproteins	500:521	N-linked glycoproteins	500:521	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	0	54	theme	drug	79:82	arg1	targets					84:90	innovative HIV-1 drug targets	62:90	innovative HIV-1 drug targets	62:90	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	5	55	theme	active	860:865	arg1	inhibitor					880:888	the active site RNase H inhibitor RDS1759	856:896	the active site RNase H inhibitor RDS1759	856:896	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	2	56	theme	control	478:484	arg1	mechanisms					486:495	the control mechanisms	474:495	the control mechanisms of N-linked glycoproteins	474:521	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	5	57	theme	RNase	872:876	arg1	inhibitor					880:888	the active site RNase H inhibitor RDS1759	856:896	the active site RNase H inhibitor RDS1759	856:896	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	8	58	theme	RT-associated	1448:1460	arg1	polymerase					1480:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase	1438:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase activity	1438:1498	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	2	59	gly	glycoproteins	509:521	arg1	glycoproteins					509:521	N-linked glycoproteins	500:521	N-linked glycoproteins	500:521	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	2	60	theme	glycoproteins	509:521	arg1	mechanisms					486:495	the control mechanisms	474:495	the control mechanisms of N-linked glycoproteins	474:521	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	8	61	theme	DNA	1476:1478	arg1	polymerase					1480:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase	1438:1489	the HIV-1 RT-associated RNA-dependent DNA polymerase activity	1438:1498	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	0	62	theme	mode	123:126	arg1	targets					84:90	innovative HIV-1 drug targets	62:90	innovative HIV-1 drug targets	62:90	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	0	62	theme	mode	123:126	arg1	characterization					96:111	characterization	96:111	characterization of Lupeol mode of action	96:136	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	2	63	dep	function	421:428	arg1	formation					523:531	formation	523:531	formation in the endoplasmic reticulum	523:560	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	2	64	theme	-associated	384:394	arg1	function					421:428	the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function	348:428	the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function	348:428	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	5	65	theme	blind	903:907	arg1	calculations					917:928	blind docking calculations	903:928	blind docking calculations	903:928	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	6	66	contain	containing	1187:1196	arg2	Lupeol					1198:1203	Lupeol	1198:1203	Lupeol	1198:1203	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	6	66	contain	containing	1187:1196	arg1	plant					1181:1185	an Ayurveda medicinal plant	1159:1185	an Ayurveda medicinal plant containing Lupeol	1159:1203	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	6	66	contain	containing	1187:1196	arg1	indicus					1150:1156	Hemidesmus indicus	1139:1156	Hemidesmus indicus	1139:1156	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	4	67	theme	pentacyclic	706:716	arg1	Lupeol					729:734	the pentacyclic triterpene Lupeol	702:734	the pentacyclic triterpene Lupeol	702:734	Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function.
28637198	0	68	theme	Hemidesmus	25:34	arg1	decoction					44:52	Hemidesmus indicus decoction	25:52	Hemidesmus indicus decoction	25:52	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	5	69	theme	calculations	917:928	arg1	studies					834:840	combination studies	822:840	combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations	822:928	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	7	70	theme	active	1278:1283	arg1	source					1290:1295	a valuable multitarget active drug source	1255:1295	a valuable multitarget active drug source	1255:1295	Results supported the potential of this plant as a valuable multitarget active drug source.
28637198	8	71	theme	active	1333:1338	arg1	metabolites					1340:1350	its numerous active metabolites	1320:1350	its numerous active metabolites	1320:1350	In fact, by virtue of its numerous active metabolites, H. indicus was able to inhibit not only the RT-associated RNase H function, but also the HIV-1 RT-associated RNA-dependent DNA polymerase activity and the cellular α-glucosidase.
28637198	2	72	theme	RNase	412:416	arg1	H					409:409	ribonuclease H	396:409	the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function	348:428	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	2	72	theme	RNase	412:416	arg1	H					418:418	RNase H	412:418	RNase H	412:418	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	0	73	theme	decoction	44:52	arg1	activity					13:20	Multi-target activity	0:20	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.	0:137	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	1	74	theme	HIV-1	311:315	arg1	targets					317:323	underexplored HIV-1 targets	297:323	underexplored HIV-1 targets	297:323	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28637198	1	75	theme	urgent	211:216	arg1	need					218:221	an urgent need	208:221	an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets	208:323	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28637198	5	76	theme	allosteric	978:987	arg1	pocket					989:994	an HIV-1 RT allosteric pocket	966:994	an HIV-1 RT allosteric pocket	966:994	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	7	77	theme	valuable	1257:1264	arg1	source					1290:1295	a valuable multitarget active drug source	1255:1295	a valuable multitarget active drug source	1255:1295	Results supported the potential of this plant as a valuable multitarget active drug source.
28637198	4	78	theme	H	792:792	arg1	function					794:801	the HIV-1 RT-associated RNase H function	762:801	the HIV-1 RT-associated RNase H function	762:801	Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function.
28637198	2	79	theme	H	409:409	arg1	function					421:428	the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function	348:428	the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function	348:428	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	0	80	theme	innovative	62:71	arg1	targets					84:90	innovative HIV-1 drug targets	62:90	innovative HIV-1 drug targets	62:90	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	2	81	theme	cellular	438:445	arg1	α-glucosidase					447:459	the cellular α-glucosidase	434:459	the cellular α-glucosidase	434:459	Among them, there are the HIV-1 reverse transcriptase (RT)-associated ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum.
28637198	0	82	dep	Hemidesmus	25:34	arg1	indicus					36:42	indicus	36:42	indicus	36:42	Multi-target activity of Hemidesmus indicus decoction against innovative HIV-1 drug targets and characterization of Lupeol mode of action.
28637198	3	83	theme	promising	643:651	arg1	class					653:657	a promising class	641:657	a promising class of HIV-1 inhibitors	641:677	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	83	theme	promising	643:651	arg1	triterpenes					624:634	pentacyclic triterpenes	612:634	pentacyclic triterpenes	612:634	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	3	83	theme	promising	643:651	arg1	compounds					593:601	many natural compounds	580:601	many natural compounds	580:601	It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors.
28637198	5	84	theme	HIV-1	969:973	arg1	RT					975:976	HIV-1 RT	969:976	an HIV-1 RT allosteric pocket	966:994	We then performed combination studies of Lupeol and the active site RNase H inhibitor RDS1759, and blind docking calculations, demonstrating that Lupeol binds to an HIV-1 RT allosteric pocket.
28637198	6	85	theme	drug	1074:1077	arg1	supplement					1079:1088	potential multitarget active drug supplement	1045:1088	potential multitarget active drug supplement	1045:1088	On the bases of these results and searching for potential multitarget active drug supplement, we also investigated the anti-HIV-1 activity of Hemidesmus indicus, an Ayurveda medicinal plant containing Lupeol.
28637198	4	86	theme	RT-associated	772:784	arg1	function					794:801	the HIV-1 RT-associated RNase H function	762:801	the HIV-1 RT-associated RNase H function	762:801	Hence, here we tested the pentacyclic triterpene Lupeol, showing that it inhibits the HIV-1 RT-associated RNase H function.
28637198	1	87	theme	therapeutic	244:254	arg1	strategies					256:265	novel therapeutic strategies	238:265	novel therapeutic strategies	238:265	Despite the availability of several anti-retrovirals, there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets.
28538154	7	0	theme	group	1090:1094	arg1	shift					1067:1071	a large blue shift	1054:1071	a large blue shift of the phosphate group at the CaCl2 solution interface	1054:1126	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	5	1	link	N-linked	728:735	arg1	chain					758:762	the N-linked saturated fatty acid chain	724:762	the N-linked saturated fatty acid chain	724:762	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	5	2	dep	they	774:777	arg1	make					779:782	make	779:782	make the sphingosine backbone	779:807	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	1	3	theme	wide	176:179	arg1	range					181:185	a wide range	174:185	a wide range of cellular activities	174:208	The interactions between Ca2+ ions and sphingomyelin play crucial roles in a wide range of cellular activities.
28538154	7	4	theme	large	1056:1060	arg1	shift					1067:1071	a large blue shift	1054:1071	a large blue shift of the phosphate group at the CaCl2 solution interface	1054:1126	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	6	5	theme	methyl	946:951	arg1	group					953:957	the methyl group	942:957	the methyl group	942:957	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	5	6	theme	Ca2+	700:703	arg1	ions					705:708	the Ca2+ ions	696:708	the Ca2+ ions	696:708	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	10	7	theme	domain	1736:1741	arg1	formation					1743:1751	lipid domain formation	1730:1751	lipid domain formation	1730:1751	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	1	8	theme	activities	199:208	arg1	range					181:185	a wide range	174:185	a wide range of cellular activities	174:208	The interactions between Ca2+ ions and sphingomyelin play crucial roles in a wide range of cellular activities.
28538154	11	9	from	interfaces	1891:1900	arg1	interactions					1841:1852	the interactions	1837:1852	the interactions of complex molecules at surfaces and interfaces	1837:1900	It will also shed light on the interactions of complex molecules at surfaces and interfaces.
28538154	5	10	theme	ESM	678:680	arg1	analysis					635:642	An analysis	632:642	An analysis of the one alkyl-chain-deuterated ESM	632:680	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	10	11	theme	structural	1768:1777	arg1	changes					1779:1785	slight structural changes	1761:1785	slight structural changes in the membrane lipid	1761:1807	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	2	12	theme	molecular	246:254	arg1	details					256:262	the molecular details	242:262	the molecular details of the interactions at interfaces	242:296	However, little is known about the molecular details of the interactions at interfaces.
28538154	9	13	theme	hydrogen	1450:1457	arg1	bond					1459:1462	the intramolecular hydrogen bond	1431:1462	the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone	1431:1581	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	6	14	theme	change	994:999	arg1	end					966:968	the end	962:968	the end of sphingosine backbone change from pointing downward to pointing upward	962:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	5	15	theme	fatty	747:751	arg1	chain					758:762	the N-linked saturated fatty acid chain	724:762	the N-linked saturated fatty acid chain	724:762	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	10	16	theme	membrane	1794:1801	arg1	lipid					1803:1807	the membrane lipid	1790:1807	the membrane lipid	1790:1807	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	1	17	theme	crucial	157:163	arg1	roles					165:169	crucial roles	157:169	crucial roles	157:169	The interactions between Ca2+ ions and sphingomyelin play crucial roles in a wide range of cellular activities.
28538154	6	18	theme	sphingosine	973:983	arg1	change					994:999	sphingosine backbone change	973:999	sphingosine backbone change from pointing downward to pointing upward	973:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	11	19	from	surfaces	1878:1885	arg1	interactions					1841:1852	the interactions	1837:1852	the interactions of complex molecules at surfaces and interfaces	1837:1900	It will also shed light on the interactions of complex molecules at surfaces and interfaces.
28538154	0	20	theme	Vibrational	73:83	arg1	Spectroscopy					85:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Effect of Ca2+ to Sphingomyelin Investigated by Sum Frequency Generation Vibrational Spectroscopy.
28538154	9	21	theme	3-hydroxyl	1476:1485	arg1	group					1487:1491	the 3-hydroxyl group	1472:1491	the 3-hydroxyl group	1472:1491	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	8	22	theme	moiety	1292:1297	arg1	change					1268:1273	the conformation change	1251:1273	the conformation change of the phosphate moiety	1251:1297	Such binding causes the phosphate moiety to dehydrate, resulting in the conformation change of the phosphate moiety.
28538154	7	23	theme	new	1157:1159	arg1	modes					1176:1180	new cation binding modes	1157:1180	new cation binding modes	1157:1180	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	2	24	theme	interactions	271:282	arg1	details					256:262	the molecular details	242:262	the molecular details of the interactions at interfaces	242:296	However, little is known about the molecular details of the interactions at interfaces.
28538154	10	25	from	changes	1779:1785	arg1	lipid					1803:1807	the membrane lipid	1790:1807	the membrane lipid	1790:1807	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	5	26	theme	N-linked	728:735	arg1	chain					758:762	the N-linked saturated fatty acid chain	724:762	the N-linked saturated fatty acid chain	724:762	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	9	27	theme	phosphate	1501:1509	arg1	oxygen					1511:1516	the phosphate oxygen	1497:1516	the phosphate oxygen	1497:1516	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	3	28	theme	egg	368:370	arg1	ESM					387:389	ESM	387:389	ESM	387:389	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	28	theme	egg	368:370	arg1	sphingomyelin					372:384	egg sphingomyelin	368:384	egg sphingomyelin (ESM) Langmuir monolayers	368:410	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	0	29	theme	Generation	62:71	arg1	Spectroscopy					85:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Effect of Ca2+ to Sphingomyelin Investigated by Sum Frequency Generation Vibrational Spectroscopy.
28538154	11	30	theme	complex	1857:1863	arg1	molecules					1865:1873	complex molecules	1857:1873	complex molecules	1857:1873	It will also shed light on the interactions of complex molecules at surfaces and interfaces.
28538154	5	31	theme	sphingosine	788:798	arg1	backbone					800:807	the sphingosine backbone	784:807	the sphingosine backbone	784:807	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	3	32	theme	subwavenumber	442:454	arg1	spectroscopy					519:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy	442:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)	442:545	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	32	theme	subwavenumber	442:454	arg1	HR-BB-SFG-VS					533:544	HR-BB-SFG-VS	533:544	HR-BB-SFG-VS	533:544	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	0	33	theme	Ca2+	10:13	arg1	Effect					0:5	Effect	0:5	Effect of Ca2+ to Sphingomyelin	0:30	Effect of Ca2+ to Sphingomyelin Investigated by Sum Frequency Generation Vibrational Spectroscopy.
28538154	6	34	theme	spectra	856:862	arg1	analysis					833:840	Further analysis	825:840	Further analysis of the SFG-VS spectra	825:862	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	2	35	from	details	256:262	arg1	interfaces					287:296	interfaces	287:296	interfaces	287:296	However, little is known about the molecular details of the interactions at interfaces.
28538154	10	36	theme	potential	1614:1622	arg1	application					1624:1634	the potential application	1610:1634	the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid	1610:1807	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	7	37	theme	solution	1109:1116	arg1	interface					1118:1126	the CaCl2 solution interface	1099:1126	the CaCl2 solution interface	1099:1126	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	0	38	theme	Frequency	52:60	arg1	Spectroscopy					85:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Effect of Ca2+ to Sphingomyelin Investigated by Sum Frequency Generation Vibrational Spectroscopy.
28538154	3	39	theme	frequency	486:494	arg1	spectroscopy					519:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy	442:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)	442:545	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	39	theme	frequency	486:494	arg1	HR-BB-SFG-VS					533:544	HR-BB-SFG-VS	533:544	HR-BB-SFG-VS	533:544	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	40	theme	broadband	472:480	arg1	spectroscopy					519:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy	442:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)	442:545	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	40	theme	broadband	472:480	arg1	HR-BB-SFG-VS					533:544	HR-BB-SFG-VS	533:544	HR-BB-SFG-VS	533:544	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	4	41	theme	acyl	598:601	arg1	chains					603:608	the acyl chains	594:608	the acyl chains	594:608	We show that Ca2+ ions can induce ordering of the acyl chains in the ESM monolayer.
28538154	10	42	theme	calcium	1701:1707	arg1	channel					1709:1715	the calcium channel	1697:1715	the calcium channel	1697:1715	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	6	43	theme	Ca2+	908:911	arg1	ions					913:916	Ca2+ ions	908:916	Ca2+ ions	908:916	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	9	44	theme	backbone	1574:1581	arg1	change					1548:1553	an ordering change	1536:1553	an ordering change of the sphingosine backbone	1536:1581	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	7	45	theme	cation	1161:1166	arg1	modes					1176:1180	new cation binding modes	1157:1180	new cation binding modes	1157:1180	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	7	46	theme	phosphate	1080:1088	arg1	group					1090:1094	the phosphate group	1076:1094	the phosphate group	1076:1094	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	3	47	theme	vibrational	507:517	arg1	spectroscopy					519:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy	442:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)	442:545	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	47	theme	vibrational	507:517	arg1	HR-BB-SFG-VS					533:544	HR-BB-SFG-VS	533:544	HR-BB-SFG-VS	533:544	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	10	48	theme	lipid	1730:1734	arg1	formation					1743:1751	lipid domain formation	1730:1751	lipid domain formation	1730:1751	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	9	49	theme	Ca2+	1364:1367	arg1	ions					1369:1372	Ca2+ ions	1364:1372	Ca2+ ions	1364:1372	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	10	50	theme	lipid-cation	1667:1678	arg1	interactions					1680:1691	lipid-cation interactions	1667:1691	lipid-cation interactions	1667:1691	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	7	51	theme	blue	1062:1065	arg1	shift					1067:1071	a large blue shift	1054:1071	a large blue shift of the phosphate group at the CaCl2 solution interface	1054:1126	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	8	52	theme	Such	1183:1186	arg1	binding					1188:1194	Such binding	1183:1194	Such binding	1183:1194	Such binding causes the phosphate moiety to dehydrate, resulting in the conformation change of the phosphate moiety.
28538154	7	53	theme	binding	1168:1174	arg1	modes					1176:1180	new cation binding modes	1157:1180	new cation binding modes	1157:1180	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	6	54	from	pointing	1006:1013	arg1	end					966:968	the end	962:968	the end of sphingosine backbone change from pointing downward to pointing upward	962:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	6	54	from	pointing	1006:1013	arg1	change					994:999	sphingosine backbone change	973:999	sphingosine backbone change from pointing downward to pointing upward	973:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	10	55	theme	slight	1761:1766	arg1	changes					1779:1785	slight structural changes	1761:1785	slight structural changes in the membrane lipid	1761:1807	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	6	56	theme	group	953:957	arg1	orientation					927:937	the orientation	923:937	the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward	923:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	9	57	theme	phosphate	1390:1398	arg1	group					1400:1404	the phosphate group	1386:1404	the phosphate group	1386:1404	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	4	58	theme	ESM	617:619	arg1	monolayer					621:629	the ESM monolayer	613:629	the ESM monolayer	613:629	We show that Ca2+ ions can induce ordering of the acyl chains in the ESM monolayer.
28538154	5	59	theme	alkyl-chain-deuterated	655:676	arg1	ESM					678:680	the one alkyl-chain-deuterated ESM	647:680	the one alkyl-chain-deuterated ESM	647:680	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	1	60	theme	Ca2+	124:127	arg1	ions					129:132	Ca2+ ions	124:132	Ca2+ ions	124:132	The interactions between Ca2+ ions and sphingomyelin play crucial roles in a wide range of cellular activities.
28538154	9	61	theme	intramolecular	1435:1448	arg1	bond					1459:1462	the intramolecular hydrogen bond	1431:1462	the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone	1431:1581	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	9	62	dep	mechanism	1349:1357	arg1	destroy					1423:1429	destroy	1423:1429	destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone	1423:1581	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	9	62	dep	mechanism	1349:1357	arg1	bind					1378:1381	bind	1378:1381	bind to the phosphate group	1378:1404	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	5	63	theme	saturated	737:745	arg1	chain					758:762	the N-linked saturated fatty acid chain	724:762	the N-linked saturated fatty acid chain	724:762	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	1	64	theme	cellular	190:197	arg1	activities					199:208	cellular activities	190:208	cellular activities	190:208	The interactions between Ca2+ ions and sphingomyelin play crucial roles in a wide range of cellular activities.
28538154	6	65	theme	backbone	985:992	arg1	change					994:999	sphingosine backbone change	973:999	sphingosine backbone change from pointing downward to pointing upward	973:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	8	66	theme	conformation	1255:1266	arg1	change					1268:1273	the conformation change	1251:1273	the conformation change of the phosphate moiety	1251:1297	Such binding causes the phosphate moiety to dehydrate, resulting in the conformation change of the phosphate moiety.
28538154	5	67	theme	acid	753:756	arg1	chain					758:762	the N-linked saturated fatty acid chain	724:762	the N-linked saturated fatty acid chain	724:762	An analysis of the one alkyl-chain-deuterated ESM revealed that the Ca2+ ions do not affect the N-linked saturated fatty acid chain, although they make the sphingosine backbone become ordered.
28538154	2	68	from	interfaces	287:296	arg1	interactions					271:282	the interactions	267:282	the interactions at interfaces	267:296	However, little is known about the molecular details of the interactions at interfaces.
28538154	2	68	from	interfaces	287:296	arg1	details					256:262	the molecular details	242:262	the molecular details of the interactions at interfaces	242:296	However, little is known about the molecular details of the interactions at interfaces.
28538154	3	69	theme	Ca2+	354:357	arg1	ions					359:362	Ca2+ ions	354:362	Ca2+ ions	354:362	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	7	70	from	interface	1118:1126	arg1	shift					1067:1071	a large blue shift	1054:1071	a large blue shift of the phosphate group at the CaCl2 solution interface	1054:1126	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	8	71	theme	phosphate	1282:1290	arg1	moiety					1292:1297	the phosphate moiety	1278:1297	the phosphate moiety	1278:1297	Such binding causes the phosphate moiety to dehydrate, resulting in the conformation change of the phosphate moiety.
28538154	3	72	theme	sum	482:484	arg1	spectroscopy					519:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy	442:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)	442:545	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	72	theme	sum	482:484	arg1	HR-BB-SFG-VS					533:544	HR-BB-SFG-VS	533:544	HR-BB-SFG-VS	533:544	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	8	73	theme	phosphate	1207:1215	arg1	moiety					1217:1222	the phosphate moiety	1203:1222	the phosphate moiety to dehydrate	1203:1235	Such binding causes the phosphate moiety to dehydrate, resulting in the conformation change of the phosphate moiety.
28538154	3	74	theme	air/water	419:427	arg1	interface					429:437	the air/water interface	415:437	the air/water interface	415:437	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	75	theme	sphingomyelin	372:384	arg1	monolayers					401:410	egg sphingomyelin (ESM) Langmuir monolayers	368:410	egg sphingomyelin (ESM) Langmuir monolayers	368:410	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	4	76	theme	Ca2+	561:564	arg1	ions					566:569	Ca2+ ions	561:569	Ca2+ ions	561:569	We show that Ca2+ ions can induce ordering of the acyl chains in the ESM monolayer.
28538154	6	77	from	end	966:968	arg1	pointing					1006:1013	pointing downward	1006:1022	pointing downward to pointing upward	1006:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	6	77	from	end	966:968	arg1	orientation					927:937	the orientation	923:937	the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward	923:1041	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	11	78	theme	molecules	1865:1873	arg1	interactions					1841:1852	the interactions	1837:1852	the interactions of complex molecules at surfaces and interfaces	1837:1900	It will also shed light on the interactions of complex molecules at surfaces and interfaces.
28538154	3	79	theme	high-resolution	456:470	arg1	spectroscopy					519:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy	442:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)	442:545	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	79	theme	high-resolution	456:470	arg1	HR-BB-SFG-VS					533:544	HR-BB-SFG-VS	533:544	HR-BB-SFG-VS	533:544	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	7	80	theme	CaCl2	1103:1107	arg1	interface					1118:1126	the CaCl2 solution interface	1099:1126	the CaCl2 solution interface	1099:1126	Moreover, a large blue shift of the phosphate group at the CaCl2 solution interface indicates, to our knowledge, new cation binding modes.
28538154	6	81	theme	SFG-VS	849:854	arg1	spectra					856:862	the SFG-VS spectra	845:862	the SFG-VS spectra	845:862	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	3	82	theme	Langmuir	392:399	arg1	monolayers					401:410	egg sphingomyelin (ESM) Langmuir monolayers	368:410	egg sphingomyelin (ESM) Langmuir monolayers	368:410	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	83	from	interface	429:437	arg1	interactions					333:344	the interactions	329:344	the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface	329:437	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	0	84	theme	Sum	48:50	arg1	Spectroscopy					85:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Sum Frequency Generation Vibrational Spectroscopy	48:96	Effect of Ca2+ to Sphingomyelin Investigated by Sum Frequency Generation Vibrational Spectroscopy.
28538154	9	85	theme	ordering	1539:1546	arg1	change					1548:1553	an ordering change	1536:1553	an ordering change of the sphingosine backbone	1536:1581	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	3	86	theme	generation	496:505	arg1	spectroscopy					519:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy	442:530	subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)	442:545	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	3	86	theme	generation	496:505	arg1	HR-BB-SFG-VS					533:544	HR-BB-SFG-VS	533:544	HR-BB-SFG-VS	533:544	In this work, we investigated the interactions between Ca2+ ions and egg sphingomyelin (ESM) Langmuir monolayers at the air/water interface by subwavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS).
28538154	6	87	theme	Further	825:831	arg1	analysis					833:840	Further analysis	825:840	Further analysis of the SFG-VS spectra	825:862	Further analysis of the SFG-VS spectra shows that the interactions between ESM and Ca2+ ions make the orientation of the methyl group at the end of sphingosine backbone change from pointing downward to pointing upward.
28538154	4	88	theme	chains	603:608	arg1	ordering					582:589	ordering	582:589	ordering of the acyl chains	582:608	We show that Ca2+ ions can induce ordering of the acyl chains in the ESM monolayer.
28538154	10	89	theme	HR-BB-SFG-VS	1639:1650	arg1	application					1624:1634	the potential application	1610:1634	the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid	1610:1807	These findings illustrate the potential application of HR-BB-SFG-VS to investigate lipid-cation interactions and the calcium channel modulated by lipid domain formation through slight structural changes in the membrane lipid.
28538154	9	90	theme	sphingosine	1562:1572	arg1	backbone					1574:1581	the sphingosine backbone	1558:1581	the sphingosine backbone	1558:1581	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28538154	9	91	theme	molecular	1339:1347	arg1	mechanism					1349:1357	the molecular mechanism	1335:1357	the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone	1335:1581	Based on these results, we propose the molecular mechanism that Ca2+ ions can bind to the phosphate group and subsequently destroy the intramolecular hydrogen bond between the 3-hydroxyl group and the phosphate oxygen, which results in an ordering change of the sphingosine backbone.
28167527	7	0	attach	present	1071:1077	arg1	proteins					1091:1098	multiple proteins	1082:1098	multiple proteins from hESC and OC	1082:1115	These structures were found to be present on multiple proteins from hESC and OC.
28167527	7	0	attach	present	1071:1077	arg2	structures					1043:1052	These structures	1037:1052	These structures	1037:1052	These structures were found to be present on multiple proteins from hESC and OC.
28167527	2	1	theme	significant	366:376	arg1	challenge					378:386	a significant challenge	364:386	a significant challenge in mAb preclinical development	364:417	Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development.
28167527	9	2	theme	B3GALT5	1354:1360	arg1	expression					1362:1371	B3GALT5 expression	1354:1371	B3GALT5 expression	1354:1371	Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures.
28167527	4	3	theme	Normal	642:647	arg1	lines					654:658	Normal cell lines	642:658	Normal cell lines	642:658	Normal cell lines and tissue were unstained by mAb-A4.
28167527	3	4	theme	present	557:563	arg1	N-glycans					547:555	N-glycans	547:555	N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested	547:639	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	10	5	theme	type	1531:1534	arg1	LacNAc					1549:1554	oncofetal H type 1 and type 1 LacNAc	1519:1554	oncofetal H type 1 and type 1 LacNAc on OC	1519:1560	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	1	6	theme	cancer	200:205	arg1	glycans					181:187	Cancer-specific glycans	165:187	Cancer-specific glycans of ovarian cancer	165:205	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	1	6	theme	cancer	200:205	arg1	epitopes					221:228	promising epitopes	211:228	promising epitopes for targeting with monoclonal antibodies (mAb)	211:275	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	10	7	theme	oncofetal	1519:1527	arg1	type					1531:1534	oncofetal H type 1	1519:1536	oncofetal H type 1	1519:1536	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	2	8	theme	structural	303:312	arg1	characterization					314:329	structural characterization	303:329	structural characterization of these glycan epitopes	303:354	Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development.
28167527	5	9	theme	glycan	801:806	arg1	microarray					808:817	glycan microarray	801:817	glycan microarray	801:817	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	6	10	theme	mAb-A4	935:940	arg1	Fucα1-2Galβ1-3GlcNAcβ					968:988	Fucα1-2Galβ1-3GlcNAcβ	968:988	Fucα1-2Galβ1-3GlcNAcβ (H type 1)	968:999	The mAb-A4 epitopes were found to be Fucα1-2Galβ1-3GlcNAcβ (H type 1) and Galβ1-3GlcNAcβ (type 1 LacNAc).
28167527	6	10	theme	mAb-A4	935:940	arg1	epitopes					942:949	The mAb-A4 epitopes	931:949	The mAb-A4 epitopes	931:949	The mAb-A4 epitopes were found to be Fucα1-2Galβ1-3GlcNAcβ (H type 1) and Galβ1-3GlcNAcβ (type 1 LacNAc).
28167527	0	11	from	epitopes	67:74	arg1	cancer					87:92	ovarian cancer	79:92	ovarian cancer	79:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	3	12	theme	mAb-A4	464:469	arg1	antibody					455:462	the monoclonal antibody	440:462	the monoclonal antibody	440:462	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	0	13	theme	anti-glycan	125:135	arg1	antibody					148:155	the anti-glycan monoclonal antibody mAb-A4	121:162	the anti-glycan monoclonal antibody mAb-A4	121:162	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	11	14	theme	orthogonal	1704:1713	arg1	framework					1715:1723	the orthogonal framework	1700:1723	the orthogonal framework used in this work	1700:1741	We propose that the orthogonal framework used in this work could be the basis for advancing anti-glycan mAb characterization.
28167527	11	14	theme	orthogonal	1704:1713	arg1	basis					1756:1760	the basis	1752:1760	the basis for advancing anti-glycan mAb characterization	1752:1807	We propose that the orthogonal framework used in this work could be the basis for advancing anti-glycan mAb characterization.
28167527	5	15	theme	mass	901:904	arg1	MALDI-MS					920:927	MALDI-MS	920:927	MALDI-MS	920:927	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	15	theme	mass	901:904	arg1	spectrometry					906:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry	831:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:928	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	16	from	epitopes	733:740	arg1	lines					753:757	OC cell lines	745:757	OC cell lines targeted by mAb-A4	745:776	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	3	17	theme	breast	609:614	arg1	lines					628:632	8 of 14 breast cancer cell lines	601:632	8 of 14 breast cancer cell lines tested	601:639	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	0	18	theme	N-acetyllactosamine	40:58	arg1	epitopes					67:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes	20:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer	20:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	9	19	theme	orthogonal	1451:1460	arg1	evidence					1462:1469	orthogonal evidence	1451:1469	orthogonal evidence of the epitopes' structures	1451:1497	Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures.
28167527	6	20	theme	H	991:991	arg1	Fucα1-2Galβ1-3GlcNAcβ					968:988	Fucα1-2Galβ1-3GlcNAcβ	968:988	Fucα1-2Galβ1-3GlcNAcβ (H type 1)	968:999	The mAb-A4 epitopes were found to be Fucα1-2Galβ1-3GlcNAcβ (H type 1) and Galβ1-3GlcNAcβ (type 1 LacNAc).
28167527	6	20	theme	H	991:991	arg1	type					993:996	H type 1	991:998	H type 1	991:998	The mAb-A4 epitopes were found to be Fucα1-2Galβ1-3GlcNAcβ (H type 1) and Galβ1-3GlcNAcβ (type 1 LacNAc).
28167527	8	21	theme	N-glycans	1275:1283	arg1	polylactosamines					1255:1270	the polylactosamines	1251:1270	the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433	1251:1319	Importantly, endo-β-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433.
28167527	7	22	located	present	1071:1077	arg1	proteins					1091:1098	multiple proteins	1082:1098	multiple proteins from hESC and OC	1082:1115	These structures were found to be present on multiple proteins from hESC and OC.
28167527	7	22	located	present	1071:1077	arg2	structures					1043:1052	These structures	1037:1052	These structures	1037:1052	These structures were found to be present on multiple proteins from hESC and OC.
28167527	0	23	theme	epitopes	67:74	arg1	Characterization					0:15	Characterization	0:15	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer	0:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	5	24	theme	laser	873:877	arg1	MALDI-MS					920:927	MALDI-MS	920:927	MALDI-MS	920:927	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	24	theme	laser	873:877	arg1	spectrometry					906:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry	831:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:928	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	0	25	from	Characterization	0:15	arg1	cancer					87:92	ovarian cancer	79:92	ovarian cancer	79:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	8	26	theme	SKOV3	1288:1292	arg1	IGROV1					1295:1300	IGROV1	1295:1300	IGROV1	1295:1300	Importantly, endo-β-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433.
28167527	0	27	theme	ovarian	79:85	arg1	cancer					87:92	ovarian cancer	79:92	ovarian cancer	79:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	7	28	from	OC	1114:1115	arg1	proteins					1091:1098	multiple proteins	1082:1098	multiple proteins from hESC and OC	1082:1115	These structures were found to be present on multiple proteins from hESC and OC.
28167527	8	29	theme	IGROV1	1295:1300	arg1	N-glycans					1275:1283	N-glycans	1275:1283	N-glycans of SKOV3, IGROV1, OV90, and OVCA433	1275:1319	Importantly, endo-β-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433.
28167527	5	30	theme	glycan	726:731	arg1	epitopes					733:740	the N-linked glycan epitopes	713:740	the N-linked glycan epitopes on OC cell lines targeted by mAb-A4	713:776	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	9	31	theme	structures	1488:1497	arg1	evidence					1462:1469	orthogonal evidence	1451:1469	orthogonal evidence of the epitopes' structures	1451:1497	Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures.
28167527	8	32	theme	OV90	1303:1306	arg1	N-glycans					1275:1283	N-glycans	1275:1283	N-glycans of SKOV3, IGROV1, OV90, and OVCA433	1275:1319	Importantly, endo-β-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433.
28167527	11	33	theme	anti-glycan	1776:1786	arg1	characterization					1792:1807	advancing anti-glycan mAb characterization	1766:1807	advancing anti-glycan mAb characterization	1766:1807	We propose that the orthogonal framework used in this work could be the basis for advancing anti-glycan mAb characterization.
28167527	0	34	theme	H	20:20	arg1	type					22:25	H type 1	20:27	H type 1	20:27	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	3	35	attach	present	557:563	arg1	lines					628:632	8 of 14 breast cancer cell lines	601:632	8 of 14 breast cancer cell lines tested	601:639	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	35	attach	present	557:563	arg2	N-glycans					547:555	N-glycans	547:555	N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested	547:639	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	35	attach	present	557:563	arg1	OC					593:594	OC	593:594	OC	593:594	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	35	attach	present	557:563	arg1	cancer					585:590	11 of 19 ovarian cancer	568:590	11 of 19 ovarian cancer (OC)	568:595	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	36	theme	embryonic	485:493	arg1	hESC					507:510	hESC	507:510	hESC	507:510	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	36	theme	embryonic	485:493	arg1	cells					500:504	human embryonic stem cells	479:504	human embryonic stem cells (hESC)	479:511	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	9	37	from	knockdown	1341:1349	arg1	SKOV3					1376:1380	SKOV3	1376:1380	SKOV3	1376:1380	Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures.
28167527	10	38	from	OC	1559:1560	arg1	recognition					1504:1514	The recognition	1500:1514	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4	1500:1570	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	10	38	from	OC	1559:1560	arg1	way					1597:1599	a novel and promising way	1575:1599	a novel and promising way to target OC	1575:1612	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	3	39	theme	cell	623:626	arg1	lines					628:632	8 of 14 breast cancer cell lines	601:632	8 of 14 breast cancer cell lines tested	601:639	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	10	40	theme	target	1604:1609	arg1	OC					1611:1612	target OC	1604:1612	target OC	1604:1612	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	0	41	theme	type	33:36	arg1	epitopes					67:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes	20:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer	20:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	5	42	used	used	782:785	arg2	we					779:780	we	779:780	we	779:780	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	2	43	theme	epitopes	347:354	arg1	characterization					314:329	structural characterization	303:329	structural characterization of these glycan epitopes	303:354	Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development.
28167527	5	44	theme	sensitivity	845:855	arg1	MALDI-MS					920:927	MALDI-MS	920:927	MALDI-MS	920:927	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	44	theme	sensitivity	845:855	arg1	spectrometry					906:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry	831:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:928	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	2	45	theme	mAb	391:393	arg1	development					407:417	mAb preclinical development	391:417	mAb preclinical development	391:417	Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development.
28167527	1	46	theme	monoclonal	249:258	arg1	mAb					272:274	mAb	272:274	mAb	272:274	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	1	46	theme	monoclonal	249:258	arg1	antibodies					260:269	monoclonal antibodies	249:269	monoclonal antibodies (mAb)	249:275	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	9	47	theme	siRNA	1335:1339	arg1	knockdown					1341:1349	siRNA knockdown	1335:1349	siRNA knockdown of B3GALT5 expression in SKOV3	1335:1380	Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures.
28167527	5	48	link	N-linked	717:724	arg1	epitopes					733:740	the N-linked glycan epitopes	713:740	the N-linked glycan epitopes on OC cell lines targeted by mAb-A4	713:776	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	9	49	theme	expression	1362:1371	arg1	knockdown					1341:1349	siRNA knockdown	1335:1349	siRNA knockdown of B3GALT5 expression in SKOV3	1335:1380	Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures.
28167527	10	50	from	LacNAc	1549:1554	arg1	OC					1559:1560	OC	1559:1560	OC	1559:1560	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	2	51	from	challenge	378:386	arg1	development					407:417	mAb preclinical development	391:417	mAb preclinical development	391:417	Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development.
28167527	5	52	theme	cell	748:751	arg1	lines					753:757	OC cell lines	745:757	OC cell lines targeted by mAb-A4	745:776	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	3	53	theme	ovarian	577:583	arg1	OC					593:594	OC	593:594	OC	593:594	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	53	theme	ovarian	577:583	arg1	cancer					585:590	11 of 19 ovarian cancer	568:590	11 of 19 ovarian cancer (OC)	568:595	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	1	54	theme	ovarian	192:198	arg1	cancer					200:205	ovarian cancer	192:205	ovarian cancer	192:205	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	4	55	theme	cell	649:652	arg1	lines					654:658	Normal cell lines	642:658	Normal cell lines	642:658	Normal cell lines and tissue were unstained by mAb-A4.
28167527	10	56	theme	H	1529:1529	arg1	type					1531:1534	oncofetal H type 1	1519:1536	oncofetal H type 1	1519:1536	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	10	57	theme	stem-like	1662:1670	arg1	phenotypes					1672:1681	stem-like phenotypes	1662:1681	stem-like phenotypes	1662:1681	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	9	58	theme	mAb-A4	1400:1405	arg1	binding					1407:1413	mAb-A4 binding	1400:1413	mAb-A4 binding	1400:1413	Furthermore, siRNA knockdown of B3GALT5 expression in SKOV3 demonstrated that mAb-A4 binding was dependent on B3GALT5, providing orthogonal evidence of the epitopes' structures.
28167527	1	59	theme	Cancer-specific	165:179	arg1	glycans					181:187	Cancer-specific glycans	165:187	Cancer-specific glycans of ovarian cancer	165:205	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	1	59	theme	Cancer-specific	165:179	arg1	epitopes					221:228	promising epitopes	211:228	promising epitopes for targeting with monoclonal antibodies (mAb)	211:275	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	8	60	theme	first	1210:1214	arg1	time					1216:1219	the first time	1206:1219	the first time	1206:1219	Importantly, endo-β-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433.
28167527	10	61	theme	LacNAc	1549:1554	arg1	recognition					1504:1514	The recognition	1500:1514	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4	1500:1570	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	10	61	theme	LacNAc	1549:1554	arg1	way					1597:1599	a novel and promising way	1575:1599	a novel and promising way to target OC	1575:1612	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	0	62	theme	monoclonal	137:146	arg1	antibody					148:155	the anti-glycan monoclonal antibody mAb-A4	121:162	the anti-glycan monoclonal antibody mAb-A4	121:162	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	5	63	theme	advanced	831:838	arg1	MALDI-MS					920:927	MALDI-MS	920:927	MALDI-MS	920:927	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	63	theme	advanced	831:838	arg1	spectrometry					906:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry	831:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:928	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	10	64	theme	type	1542:1545	arg1	LacNAc					1549:1554	oncofetal H type 1 and type 1 LacNAc	1519:1554	oncofetal H type 1 and type 1 LacNAc on OC	1519:1560	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	5	65	theme	desorption/ionization	879:899	arg1	MALDI-MS					920:927	MALDI-MS	920:927	MALDI-MS	920:927	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	65	theme	desorption/ionization	879:899	arg1	spectrometry					906:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry	831:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:928	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	7	66	from	hESC	1105:1108	arg1	proteins					1091:1098	multiple proteins	1082:1098	multiple proteins from hESC and OC	1082:1115	These structures were found to be present on multiple proteins from hESC and OC.
28167527	0	67	from	cancer	87:92	arg1	Characterization					0:15	Characterization	0:15	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer	0:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	0	68	theme	glycan	60:65	arg1	epitopes					67:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes	20:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer	20:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	5	69	theme	high	840:843	arg1	MALDI-MS					920:927	MALDI-MS	920:927	MALDI-MS	920:927	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	69	theme	high	840:843	arg1	spectrometry					906:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry	831:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:928	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	70	theme	OC	745:746	arg1	lines					753:757	OC cell lines	745:757	OC cell lines targeted by mAb-A4	745:776	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	71	theme	matrix-assisted	857:871	arg1	MALDI-MS					920:927	MALDI-MS	920:927	MALDI-MS	920:927	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	5	71	theme	matrix-assisted	857:871	arg1	spectrometry					906:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry	831:917	advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:928	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	2	72	theme	glycan	340:345	arg1	epitopes					347:354	these glycan epitopes	334:354	these glycan epitopes	334:354	Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development.
28167527	5	73	theme	N-linked	717:724	arg1	epitopes					733:740	the N-linked glycan epitopes	713:740	the N-linked glycan epitopes on OC cell lines targeted by mAb-A4	713:776	To characterize the N-linked glycan epitopes on OC cell lines targeted by mAb-A4, we used glycosidases, glycan microarray, siRNA, and advanced high sensitivity matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
28167527	1	74	theme	promising	211:219	arg1	glycans					181:187	Cancer-specific glycans	165:187	Cancer-specific glycans of ovarian cancer	165:205	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	1	74	theme	promising	211:219	arg1	epitopes					221:228	promising epitopes	211:228	promising epitopes for targeting with monoclonal antibodies (mAb)	211:275	Cancer-specific glycans of ovarian cancer are promising epitopes for targeting with monoclonal antibodies (mAb).
28167527	3	75	theme	human	479:483	arg1	hESC					507:510	hESC	507:510	hESC	507:510	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	75	theme	human	479:483	arg1	cells					500:504	human embryonic stem cells	479:504	human embryonic stem cells (hESC)	479:511	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	11	76	theme	mAb	1788:1790	arg1	characterization					1792:1807	advancing anti-glycan mAb characterization	1766:1807	advancing anti-glycan mAb characterization	1766:1807	We propose that the orthogonal framework used in this work could be the basis for advancing anti-glycan mAb characterization.
28167527	0	77	theme	type	22:25	arg1	epitopes					67:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes	20:74	H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer	20:92	Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4.
28167527	6	78	theme	type	1021:1024	arg1	LacNAc					1028:1033	type 1 LacNAc	1021:1033	type 1 LacNAc	1021:1033	The mAb-A4 epitopes were found to be Fucα1-2Galβ1-3GlcNAcβ (H type 1) and Galβ1-3GlcNAcβ (type 1 LacNAc).
28167527	6	78	theme	type	1021:1024	arg1	Galβ1-3GlcNAcβ					1005:1018	Galβ1-3GlcNAcβ	1005:1018	Galβ1-3GlcNAcβ (type 1 LacNAc)	1005:1034	The mAb-A4 epitopes were found to be Fucα1-2Galβ1-3GlcNAcβ (H type 1) and Galβ1-3GlcNAcβ (type 1 LacNAc).
28167527	10	79	theme	novel	1577:1581	arg1	recognition					1504:1514	The recognition	1500:1514	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4	1500:1570	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	10	79	theme	novel	1577:1581	arg1	way					1597:1599	a novel and promising way	1575:1599	a novel and promising way to target OC	1575:1612	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	3	80	theme	monoclonal	444:453	arg1	antibody					455:462	the monoclonal antibody	440:462	the monoclonal antibody	440:462	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	81	theme	cancer	616:621	arg1	lines					628:632	8 of 14 breast cancer cell lines	601:632	8 of 14 breast cancer cell lines tested	601:639	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	8	82	theme	OVCA433	1313:1319	arg1	N-glycans					1275:1283	N-glycans	1275:1283	N-glycans of SKOV3, IGROV1, OV90, and OVCA433	1275:1319	Importantly, endo-β-galactosidase coupled with MALDI-MS allowed these two epitopes, for the first time, to be directly identified on the polylactosamines of N-glycans of SKOV3, IGROV1, OV90, and OVCA433.
28167527	3	83	theme	stem	495:498	arg1	hESC					507:510	hESC	507:510	hESC	507:510	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	3	83	theme	stem	495:498	arg1	cells					500:504	human embryonic stem cells	479:504	human embryonic stem cells (hESC)	479:511	Our group generated the monoclonal antibody mAb-A4 against human embryonic stem cells (hESC), which also bound specifically to N-glycans present on 11 of 19 ovarian cancer (OC) and 8 of 14 breast cancer cell lines tested.
28167527	7	84	theme	multiple	1082:1089	arg1	proteins					1091:1098	multiple proteins	1082:1098	multiple proteins from hESC and OC	1082:1115	These structures were found to be present on multiple proteins from hESC and OC.
28167527	2	85	theme	preclinical	395:405	arg1	development					407:417	mAb preclinical development	391:417	mAb preclinical development	391:417	Despite their potential, structural characterization of these glycan epitopes remains a significant challenge in mAb preclinical development.
28167527	10	86	theme	promising	1587:1595	arg1	recognition					1504:1514	The recognition	1500:1514	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4	1500:1570	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	10	86	theme	promising	1587:1595	arg1	way					1597:1599	a novel and promising way	1575:1599	a novel and promising way to target OC	1575:1612	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	10	87	from	recognition	1504:1514	arg1	OC					1559:1560	OC	1559:1560	OC	1559:1560	The recognition of oncofetal H type 1 and type 1 LacNAc on OC by mAb-A4 is a novel and promising way to target OC and supports the theory that cancer can acquire stem-like phenotypes.
28167527	11	88	theme	advancing	1766:1774	arg1	characterization					1792:1807	advancing anti-glycan mAb characterization	1766:1807	advancing anti-glycan mAb characterization	1766:1807	We propose that the orthogonal framework used in this work could be the basis for advancing anti-glycan mAb characterization.
28348171	6	0	theme	novel	831:835	arg1	method					837:842	a novel method	829:842	a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF)	829:1116	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	10	1	theme	flow	1806:1809	arg1	cytometry					1811:1819	flow cytometry	1806:1819	flow cytometry	1806:1819	Using mCRPC tissues from rapid autopsies, we were able to determine M2 macrophage infiltration by using immunohistochemistry and flow cytometry.
28348171	5	2	from	target	720:725	arg1	cancer					739:744	prostate cancer	730:744	prostate cancer	730:744	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	6	3	theme	CD14+	912:916	arg1	monocytes					918:926	human CD14+ monocytes	906:926	human CD14+ monocytes	906:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	7	4	theme	surface	1140:1146	arg1	glycoproteins					1148:1160	enriched surface glycoproteins	1131:1160	enriched surface glycoproteins	1131:1160	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	10	5	from	autopsies	1708:1716	arg1	tissues					1689:1695	mCRPC tissues	1683:1695	mCRPC tissues from rapid autopsies	1683:1716	Using mCRPC tissues from rapid autopsies, we were able to determine M2 macrophage infiltration by using immunohistochemistry and flow cytometry.
28348171	10	6	theme	mCRPC	1683:1687	arg1	tissues					1689:1695	mCRPC tissues	1683:1695	mCRPC tissues from rapid autopsies	1683:1716	Using mCRPC tissues from rapid autopsies, we were able to determine M2 macrophage infiltration by using immunohistochemistry and flow cytometry.
28348171	6	7	theme	M2	800:801	arg1	macrophages					803:813	M2 macrophages	800:813	M2 macrophages	800:813	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	11	8	theme	human	1890:1894	arg1	mCRPC					1896:1900	human mCRPC	1890:1900	human mCRPC	1890:1900	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	11	9	theme	localized	1969:1977	arg1	disease					1979:1985	localized disease	1969:1985	localized disease	1969:1985	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	4	10	theme	tumor-associated	463:478	arg1	macrophages					480:490	M2 tumor-associated macrophages	460:490	M2 tumor-associated macrophages (M2-TAMs)	460:500	They are phenotypically similar to M2 tumor-associated macrophages (M2-TAMs) and have been reported to associate with solid tumors and aide in proliferation, metastasis, and resistance to therapy.
28348171	4	10	theme	tumor-associated	463:478	arg1	M2-TAMs					493:499	M2-TAMs	493:499	M2-TAMs	493:499	They are phenotypically similar to M2 tumor-associated macrophages (M2-TAMs) and have been reported to associate with solid tumors and aide in proliferation, metastasis, and resistance to therapy.
28348171	5	11	theme	prostate	730:737	arg1	cancer					739:744	prostate cancer	730:744	prostate cancer	730:744	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	0	12	theme	Macrophage-enriched	22:40	arg1	Glycoproteins					42:54	Macrophage-enriched Glycoproteins	22:54	Macrophage-enriched Glycoproteins	22:54	The Identification of Macrophage-enriched Glycoproteins Using Glycoproteomics.
28348171	11	13	theme	surface	1911:1917	arg1	glycoproteins					1919:1931	surface glycoproteins	1911:1931	the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies	1847:2014	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	2	14	theme	surgical	221:228	arg1	resection					230:238	surgical resection	221:238	surgical resection	221:238	Whereas the localized disease is highly treatable by surgical resection and radiation, cancer that has metastasized remains incurable.
28348171	6	15	theme	M1	955:956	arg1	macrophages					958:968	These homogeneous M1 macrophages	937:968	These homogeneous M1 macrophages	937:968	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	3	16	theme	Immune	303:308	arg1	cells					310:314	Immune cells	303:314	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair	303:403	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair are M2 macrophages.
28348171	3	16	theme	Immune	303:308	arg1	macrophages					412:422	M2 macrophages	409:422	M2 macrophages	409:422	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair are M2 macrophages.
28348171	5	17	theme	ideal	702:706	arg1	target					720:725	an ideal therapeutic target	699:725	an ideal therapeutic target in prostate cancer	699:744	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	5	17	theme	ideal	702:706	arg1	species					637:643	an invasive species	625:643	an invasive species within the tumor microenvironment	625:677	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	11	18	attach	presence	1851:1858	arg2	infiltration					1874:1885	macrophage infiltration	1863:1885	macrophage infiltration	1863:1885	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	11	18	attach	presence	1851:1858	arg1	mCRPC					1896:1900	human mCRPC	1890:1900	human mCRPC	1890:1900	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	1	19	theme	United	153:158	arg1	States					160:165	the United States	149:165	the United States	149:165	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	8	20	theme	human	1410:1414	arg1	macrophages					1419:1429	human M2 macrophages	1410:1429	human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes	1410:1488	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	11	21	theme	infiltration	1874:1885	arg1	glycoproteins					1919:1931	surface glycoproteins	1911:1931	the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies	1847:2014	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	11	21	theme	infiltration	1874:1885	arg1	presence					1851:1858	the presence	1847:1858	the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies	1847:2014	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	9	22	theme	human	1608:1612	arg1	mCRPC					1661:1665	mCRPC	1661:1665	mCRPC	1661:1665	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	9	22	theme	human	1608:1612	arg1	cancer					1653:1658	human metastatic castrate-resistant prostate cancer	1608:1658	human metastatic castrate-resistant prostate cancer (mCRPC) tissues	1608:1674	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	9	23	theme	castrate-resistant	1625:1642	arg1	mCRPC					1661:1665	mCRPC	1661:1665	mCRPC	1661:1665	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	9	23	theme	castrate-resistant	1625:1642	arg1	cancer					1653:1658	human metastatic castrate-resistant prostate cancer	1608:1658	human metastatic castrate-resistant prostate cancer (mCRPC) tissues	1608:1674	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	6	24	theme	M2	1014:1015	arg1	macrophages					1017:1027	our M2 macrophages	1010:1027	our M2 macrophages	1010:1027	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	3	25	theme	prostate	359:366	arg1	angiogenesis					375:386	prostate cancer angiogenesis	359:386	prostate cancer angiogenesis	359:386	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair are M2 macrophages.
28348171	7	26	theme	chromatography-tandem	1249:1269	arg1	LC-MS/MS					1290:1297	LC-MS/MS	1290:1297	LC-MS/MS	1290:1297	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	7	26	theme	chromatography-tandem	1249:1269	arg1	spectrometry					1276:1287	liquid chromatography-tandem mass spectrometry	1242:1287	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1242:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	9	27	theme	cancer	1653:1658	arg1	tissues					1668:1674	human metastatic castrate-resistant prostate cancer (mCRPC) tissues	1608:1674	human metastatic castrate-resistant prostate cancer (mCRPC) tissues	1608:1674	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	8	28	theme	M1	1449:1450	arg1	macrophages					1452:1462	human M1 macrophages	1443:1462	human M1 macrophages	1443:1462	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	7	29	theme	enriched	1131:1138	arg1	glycoproteins					1148:1160	enriched surface glycoproteins	1131:1160	enriched surface glycoproteins	1131:1160	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	3	30	theme	wound	392:396	arg1	repair					398:403	wound repair	392:403	wound repair	392:403	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair are M2 macrophages.
28348171	7	31	theme	glycopeptides	1216:1228	arg1	extraction					1193:1202	solid-phase extraction	1181:1202	solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1181:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	6	32	theme	macrophages	889:899	arg1	populations					868:878	homogeneous populations	856:878	homogeneous populations of human macrophages from human CD14+ monocytes	856:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	1	33	theme	cancer-related	117:130	arg1	deaths					132:137	cancer-related deaths	117:137	cancer-related deaths of men	117:144	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	6	34	theme	growth	1097:1102	arg1	VEGF					1112:1115	VEGF	1112:1115	VEGF	1112:1115	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	34	theme	growth	1097:1102	arg1	factor					1104:1109	vascular endothelial growth factor	1076:1109	anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF)	1037:1116	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	2	35	theme	localized	180:188	arg1	disease					190:196	the localized disease	176:196	the localized disease	176:196	Whereas the localized disease is highly treatable by surgical resection and radiation, cancer that has metastasized remains incurable.
28348171	2	35	theme	localized	180:188	arg1	treatable					208:216	treatable	208:216	treatable	208:216	Whereas the localized disease is highly treatable by surgical resection and radiation, cancer that has metastasized remains incurable.
28348171	8	36	theme	CD14+	1474:1478	arg1	monocytes					1480:1488	human CD14+ monocytes	1468:1488	human CD14+ monocytes	1468:1488	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	10	37	theme	M2	1745:1746	arg1	infiltration					1759:1770	M2 macrophage infiltration	1745:1770	M2 macrophage infiltration	1745:1770	Using mCRPC tissues from rapid autopsies, we were able to determine M2 macrophage infiltration by using immunohistochemistry and flow cytometry.
28348171	0	38	theme	Glycoproteins	42:54	arg1	Identification					4:17	The Identification	0:17	The Identification of Macrophage-enriched Glycoproteins	0:54	The Identification of Macrophage-enriched Glycoproteins Using Glycoproteomics.
28348171	6	39	theme	vascular	1076:1083	arg1	VEGF					1112:1115	VEGF	1112:1115	VEGF	1112:1115	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	39	theme	vascular	1076:1083	arg1	factor					1104:1109	vascular endothelial growth factor	1076:1109	anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF)	1037:1116	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	4	40	theme	solid	543:547	arg1	tumors					549:554	solid tumors	543:554	solid tumors	543:554	They are phenotypically similar to M2 tumor-associated macrophages (M2-TAMs) and have been reported to associate with solid tumors and aide in proliferation, metastasis, and resistance to therapy.
28348171	11	41	gly	glycoproteins	1919:1931	arg1	glycoproteins					1919:1931	surface glycoproteins	1911:1931	the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies	1847:2014	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	7	42	theme	solid-phase	1181:1191	arg1	extraction					1193:1202	solid-phase extraction	1181:1202	solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1181:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	1	43	theme	deaths	132:137	arg1	cause					108:112	a leading cause	98:112	a leading cause of cancer-related deaths of men in the United States	98:165	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	1	43	theme	deaths	132:137	arg1	cancer					88:93	Prostate cancer	79:93	Prostate cancer	79:93	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	6	44	theme	homogeneous	856:866	arg1	populations					868:878	homogeneous populations	856:878	homogeneous populations of human macrophages from human CD14+ monocytes	856:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	45	theme	novel	759:763	arg1	glycoproteins					773:785	novel surface glycoproteins	759:785	novel surface glycoproteins expressed on M2 macrophages	759:813	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	7	46	gly	glycopeptides	1216:1228	arg2	glycopeptides					1216:1228	N-linked glycopeptides	1207:1228	N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1207:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	11	47	theme	disease	1979:1985	arg1	prognosis					1956:1964	prognosis	1956:1964	prognosis of localized disease	1956:1985	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	1	48	from	cause	108:112	arg1	States					160:165	the United States	149:165	the United States	149:165	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	6	49	theme	homogeneous	943:953	arg1	macrophages					958:968	These homogeneous M1 macrophages	937:968	These homogeneous M1 macrophages	937:968	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	5	50	theme	tumor	656:660	arg1	microenvironment					662:677	the tumor microenvironment	652:677	the tumor microenvironment	652:677	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	11	51	from	glycoproteins	1919:1931	arg1	mCRPC					1896:1900	human mCRPC	1890:1900	human mCRPC	1890:1900	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	11	52	used	used	1947:1950	arg2	glycoproteins					1919:1931	surface glycoproteins	1911:1931	the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies	1847:2014	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	7	53	theme	homogeneous	1307:1317	arg1	populations					1330:1340	our homogeneous macrophage populations	1303:1340	our homogeneous macrophage populations	1303:1340	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	6	54	from	monocytes	918:926	arg1	populations					868:878	homogeneous populations	856:878	homogeneous populations of human macrophages from human CD14+ monocytes	856:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	54	from	monocytes	918:926	arg1	macrophages					889:899	human macrophages	883:899	human macrophages from human CD14+ monocytes	883:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	5	55	theme	invasive	628:635	arg1	target					720:725	an ideal therapeutic target	699:725	an ideal therapeutic target in prostate cancer	699:744	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	5	55	theme	invasive	628:635	arg1	species					637:643	an invasive species	625:643	an invasive species within the tumor microenvironment	625:677	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	6	56	theme	human	906:910	arg1	monocytes					918:926	human CD14+ monocytes	906:926	human CD14+ monocytes	906:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	57	theme	anti-inflammatory	1037:1053	arg1	cytokines					1055:1063	anti-inflammatory cytokines	1037:1063	anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF)	1037:1116	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	58	from	populations	868:878	arg1	monocytes					918:926	human CD14+ monocytes	906:926	human CD14+ monocytes	906:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	9	59	theme	surface	1528:1534	arg1	glycoproteins					1536:1548	these surface glycoproteins	1522:1548	these surface glycoproteins	1522:1548	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	5	60	theme	therapeutic	708:718	arg1	target					720:725	an ideal therapeutic target	699:725	an ideal therapeutic target in prostate cancer	699:744	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	5	60	theme	therapeutic	708:718	arg1	species					637:643	an invasive species	625:643	an invasive species within the tumor microenvironment	625:677	As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer.
28348171	6	61	theme	pro-inflammatory	978:993	arg1	cytokines					995:1003	pro-inflammatory cytokines	978:1003	pro-inflammatory cytokines	978:1003	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	9	62	gly	glycoproteins	1536:1548	arg1	glycoproteins					1536:1548	these surface glycoproteins	1522:1548	these surface glycoproteins	1522:1548	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	7	63	gly	glycoproteins	1148:1160	arg1	glycoproteins					1148:1160	enriched surface glycoproteins	1131:1160	enriched surface glycoproteins	1131:1160	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	10	64	theme	rapid	1702:1706	arg1	autopsies					1708:1716	rapid autopsies	1702:1716	rapid autopsies	1702:1716	Using mCRPC tissues from rapid autopsies, we were able to determine M2 macrophage infiltration by using immunohistochemistry and flow cytometry.
28348171	9	65	theme	M2	1569:1570	arg1	macrophages					1572:1582	M2 macrophages	1569:1582	M2 macrophages	1569:1582	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	8	66	theme	novel	1362:1366	arg1	peptides					1368:1375	five novel peptides	1357:1375	five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes	1357:1488	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	7	67	link	N-linked	1207:1214	arg1	glycopeptides					1216:1228	N-linked glycopeptides	1207:1228	N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1207:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	1	68	theme	men	142:144	arg1	deaths					132:137	cancer-related deaths	117:137	cancer-related deaths of men	117:144	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	11	69	from	presence	1851:1858	arg1	mCRPC					1896:1900	human mCRPC	1890:1900	human mCRPC	1890:1900	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	4	70	theme	M2	460:461	arg1	macrophages					480:490	M2 tumor-associated macrophages	460:490	M2 tumor-associated macrophages (M2-TAMs)	460:500	They are phenotypically similar to M2 tumor-associated macrophages (M2-TAMs) and have been reported to associate with solid tumors and aide in proliferation, metastasis, and resistance to therapy.
28348171	4	70	theme	M2	460:461	arg1	M2-TAMs					493:499	M2-TAMs	493:499	M2-TAMs	493:499	They are phenotypically similar to M2 tumor-associated macrophages (M2-TAMs) and have been reported to associate with solid tumors and aide in proliferation, metastasis, and resistance to therapy.
28348171	9	71	theme	metastatic	1614:1623	arg1	mCRPC					1661:1665	mCRPC	1661:1665	mCRPC	1661:1665	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	9	71	theme	metastatic	1614:1623	arg1	cancer					1653:1658	human metastatic castrate-resistant prostate cancer	1608:1658	human metastatic castrate-resistant prostate cancer (mCRPC) tissues	1608:1674	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	6	72	gly	glycoproteins	773:785	arg1	glycoproteins					773:785	novel surface glycoproteins	759:785	novel surface glycoproteins expressed on M2 macrophages	759:813	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	7	73	theme	mass	1271:1274	arg1	LC-MS/MS					1290:1297	LC-MS/MS	1290:1297	LC-MS/MS	1290:1297	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	7	73	theme	mass	1271:1274	arg1	spectrometry					1276:1287	liquid chromatography-tandem mass spectrometry	1242:1287	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1242:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	1	74	theme	Prostate	79:86	arg1	cause					108:112	a leading cause	98:112	a leading cause of cancer-related deaths of men in the United States	98:165	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	1	74	theme	Prostate	79:86	arg1	cancer					88:93	Prostate cancer	79:93	Prostate cancer	79:93	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	8	75	theme	M2	1416:1417	arg1	macrophages					1419:1429	human M2 macrophages	1410:1429	human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes	1410:1488	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	11	76	theme	macrophage	1863:1872	arg1	infiltration					1874:1885	macrophage infiltration	1863:1885	macrophage infiltration	1863:1885	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	7	77	theme	liquid	1242:1247	arg1	LC-MS/MS					1290:1297	LC-MS/MS	1290:1297	LC-MS/MS	1290:1297	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	7	77	theme	liquid	1242:1247	arg1	spectrometry					1276:1287	liquid chromatography-tandem mass spectrometry	1242:1287	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1242:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	9	78	theme	prostate	1644:1651	arg1	mCRPC					1661:1665	mCRPC	1661:1665	mCRPC	1661:1665	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	9	78	theme	prostate	1644:1651	arg1	cancer					1653:1658	human metastatic castrate-resistant prostate cancer	1608:1658	human metastatic castrate-resistant prostate cancer (mCRPC) tissues	1608:1674	Finally, we determined whether these surface glycoproteins, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues.
28348171	3	79	theme	cancer	368:373	arg1	angiogenesis					375:386	prostate cancer angiogenesis	359:386	prostate cancer angiogenesis	359:386	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair are M2 macrophages.
28348171	8	80	theme	relative	1431:1438	arg1	macrophages					1419:1429	human M2 macrophages	1410:1429	human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes	1410:1488	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	1	81	theme	leading	100:106	arg1	cause					108:112	a leading cause	98:112	a leading cause of cancer-related deaths of men in the United States	98:165	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	1	81	theme	leading	100:106	arg1	cancer					88:93	Prostate cancer	79:93	Prostate cancer	79:93	Prostate cancer is a leading cause of cancer-related deaths of men in the United States.
28348171	3	82	theme	M2	409:410	arg1	cells					310:314	Immune cells	303:314	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair	303:403	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair are M2 macrophages.
28348171	3	82	theme	M2	409:410	arg1	macrophages					412:422	M2 macrophages	409:422	M2 macrophages	409:422	Immune cells that primarily scavenge debris and promote prostate cancer angiogenesis and wound repair are M2 macrophages.
28348171	8	83	theme	human	1443:1447	arg1	macrophages					1452:1462	human M1 macrophages	1443:1462	human M1 macrophages	1443:1462	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	11	84	theme	targeting	1995:2003	arg1	strategies					2005:2014	targeting strategies	1995:2014	targeting strategies	1995:2014	These findings highlight the presence of macrophage infiltration in human mCRPC but also surface glycoproteins that could be used for prognosis of localized disease and for targeting strategies.
28348171	7	85	theme	N-linked	1207:1214	arg1	glycopeptides					1216:1228	N-linked glycopeptides	1207:1228	N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)	1207:1298	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
28348171	10	86	theme	macrophage	1748:1757	arg1	infiltration					1759:1770	M2 macrophage infiltration	1745:1770	M2 macrophage infiltration	1745:1770	Using mCRPC tissues from rapid autopsies, we were able to determine M2 macrophage infiltration by using immunohistochemistry and flow cytometry.
28348171	6	87	theme	human	883:887	arg1	macrophages					889:899	human macrophages	883:899	human macrophages from human CD14+ monocytes	883:926	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	88	theme	endothelial	1085:1095	arg1	VEGF					1112:1115	VEGF	1112:1115	VEGF	1112:1115	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	6	88	theme	endothelial	1085:1095	arg1	factor					1104:1109	vascular endothelial growth factor	1076:1109	anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF)	1037:1116	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	8	89	theme	human	1468:1472	arg1	monocytes					1480:1488	human CD14+ monocytes	1468:1488	human CD14+ monocytes	1468:1488	We discovered five novel peptides that are enriched exclusively on human M2 macrophages relative to human M1 macrophages and human CD14+ monocytes.
28348171	6	90	theme	surface	765:771	arg1	glycoproteins					773:785	novel surface glycoproteins	759:785	novel surface glycoproteins expressed on M2 macrophages	759:813	To identify novel surface glycoproteins expressed on M2 macrophages, we developed a novel method of creating homogeneous populations of human macrophages from human CD14+ monocytes in vitro These homogeneous M1 macrophages secrete pro-inflammatory cytokines, and our M2 macrophages secrete anti-inflammatory cytokines as well as vascular endothelial growth factor (VEGF).
28348171	7	91	theme	macrophage	1319:1328	arg1	populations					1330:1340	our homogeneous macrophage populations	1303:1340	our homogeneous macrophage populations	1303:1340	To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on our homogeneous macrophage populations.
31623829	11	0	theme	renal	1396:1400	arg1	pathology					1402:1410	The renal pathology	1392:1410	The renal pathology	1392:1410	The renal pathology, fibrosis, and podocyte injury were mitigated significantly by inhibiting core fucosylation.
31623829	6	1	theme	Fut8	911:914	arg1	gene					916:919	Fut8 gene	911:919	Fut8 gene	911:919	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted was constructed for diabetes induction.
31623829	11	2	theme	podocyte	1427:1434	arg1	injury					1436:1441	podocyte injury	1427:1441	podocyte injury	1427:1441	The renal pathology, fibrosis, and podocyte injury were mitigated significantly by inhibiting core fucosylation.
31623829	9	3	theme	body-weight	1209:1219	arg1	RESULTS					1125:1131	RESULTS The levels	1125:1142	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR)	1125:1265	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	3	4	theme	kidney	580:585	arg1	DKD					596:598	DKD	596:598	DKD	596:598	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	3	4	theme	kidney	580:585	arg1	disease					587:593	diabetic kidney disease	571:593	diabetic kidney disease (DKD)	571:599	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	2	5	gly	fucosylation	273:284	arg1	processes					320:328	various biological processes	301:328	various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation	301:405	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	5	gly	fucosylation	273:284	arg1	regulation					396:405	immune regulation	389:405	immune regulation	389:405	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	5	gly	fucosylation	273:284	arg1	apoptosis					358:366	apoptosis	358:366	apoptosis	358:366	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	5	gly	fucosylation	273:284	arg1	proliferation					343:355	cell proliferation	338:355	cell proliferation	338:355	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	5	gly	fucosylation	273:284	arg1	differentiation					369:383	differentiation	369:383	differentiation	369:383	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	1	6	theme	N-linked	194:201	arg1	glycoproteins					208:220	the N-linked type glycoproteins	190:220	the N-linked type glycoproteins	190:220	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	12	7	theme	kinase	1660:1665	arg1	ERK					1668:1670	extracellular signal-regulated kinase (ERK)	1629:1671	extracellular signal-regulated kinase (ERK)	1629:1671	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	4	8	theme	protective	650:659	arg1	effects					661:667	protective effects	650:667	protective effects	650:667	This study aimed to clarify the protective effects and molecular mechanisms during the progress of DKD by inhibiting core fucosylation in vivo.
31623829	9	9	theme	albumin-to-creatinine	1239:1259	arg1	RESULTS					1125:1131	RESULTS The levels	1125:1142	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR)	1125:1265	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	2	10	theme	biological	309:318	arg1	processes					320:328	various biological processes	301:328	various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation	301:405	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	10	theme	biological	309:318	arg1	regulation					396:405	immune regulation	389:405	immune regulation	389:405	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	10	theme	biological	309:318	arg1	apoptosis					358:366	apoptosis	358:366	apoptosis	358:366	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	10	theme	biological	309:318	arg1	proliferation					343:355	cell proliferation	338:355	cell proliferation	338:355	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	10	theme	biological	309:318	arg1	differentiation					369:383	differentiation	369:383	differentiation	369:383	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	1	11	theme	glycoproteins	208:220	arg1	core-GlcNAc					175:185	core-GlcNAc	175:185	core-GlcNAc of the N-linked type glycoproteins	175:220	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	12	12	theme	ERK	1668:1670	arg1	phosphorylation					1598:1612	the phosphorylation	1594:1612	the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK)	1594:1671	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	12	13	theme	Smad2/3	1617:1623	arg1	phosphorylation					1598:1612	the phosphorylation	1594:1612	the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK)	1594:1671	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	4	14	theme	core	735:738	arg1	fucosylation					740:751	core fucosylation in vivo	735:759	core fucosylation in vivo	735:759	This study aimed to clarify the protective effects and molecular mechanisms during the progress of DKD by inhibiting core fucosylation in vivo.
31623829	12	15	theme	extracellular	1629:1641	arg1	ERK					1668:1670	extracellular signal-regulated kinase (ERK)	1629:1671	extracellular signal-regulated kinase (ERK)	1629:1671	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	2	16	theme	Core	268:271	arg1	fucosylation					273:284	Core fucosylation	268:284	Core fucosylation	268:284	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	1	17	theme	fucose	141:146	arg1	residue					148:154	a fucose residue	139:154	a fucose residue from GDP-fucose	139:170	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	0	18	theme	kidney	63:68	arg1	disease					70:76	diabetic kidney disease	54:76	diabetic kidney disease	54:76	Inhibition of core fucosylation limits progression of diabetic kidney disease.
31623829	3	19	theme	diabetic	571:578	arg1	DKD					596:598	DKD	596:598	DKD	596:598	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	3	19	theme	diabetic	571:578	arg1	disease					587:593	diabetic kidney disease	571:593	diabetic kidney disease (DKD)	571:599	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	7	20	theme	renal	986:990	arg1	parameters					992:1001	Metabolic and renal parameters	972:1001	Metabolic and renal parameters	972:1001	Metabolic and renal parameters were measured.
31623829	12	21	theme	phosphorylation	1598:1612	arg1	downregulated					1577:1589	downregulated	1577:1589	downregulated	1577:1589	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	13	22	theme	intervention	1754:1765	arg1	strategy					1767:1774	a promising intervention strategy	1742:1774	a promising intervention strategy	1742:1774	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	13	22	theme	intervention	1754:1765	arg1	treatment					1723:1731	FUT8-based treatment	1712:1731	FUT8-based treatment	1712:1731	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	1	23	from	GDP-fucose	161:170	arg1	residue					148:154	a fucose residue	139:154	a fucose residue from GDP-fucose	139:170	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	5	24	theme	METHODS	762:768	arg1	fucosylation					775:786	METHODS Core fucosylation	762:786	METHODS Core fucosylation	762:786	METHODS Core fucosylation was examined in streptozotocin (STZ)-induced diabetic mouse model.
31623829	1	25	theme	BACKGROUND	79:88	arg1	fucosylation					109:120	BACKGROUND FUT8-mediated core fucosylation	79:120	BACKGROUND FUT8-mediated core fucosylation	79:120	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	3	26	theme	core	458:461	arg1	fucosylation					463:474	inhibiting core fucosylation	447:474	inhibiting core fucosylation	447:474	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	5	27	theme	mouse	842:846	arg1	model					848:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	METHODS Core fucosylation was examined in streptozotocin (STZ)-induced diabetic mouse model.
31623829	1	28	theme	core	104:107	arg1	fucosylation					109:120	BACKGROUND FUT8-mediated core fucosylation	79:120	BACKGROUND FUT8-mediated core fucosylation	79:120	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	5	29	gly	fucosylation	775:786	arg1	model					848:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	METHODS Core fucosylation was examined in streptozotocin (STZ)-induced diabetic mouse model.
31623829	10	30	theme	urine	1320:1324	arg1	ACR					1326:1328	KW/BW and urine ACR	1310:1328	KW/BW and urine ACR	1310:1328	KW/BW and urine ACR were decreased significantly by inhibiting core fucosylation.
31623829	0	31	theme	core	14:17	arg1	fucosylation					19:30	core fucosylation	14:30	core fucosylation	14:30	Inhibition of core fucosylation limits progression of diabetic kidney disease.
31623829	12	32	theme	inhibiting	1531:1540	arg1	fucosylation					1547:1558	inhibiting core fucosylation	1531:1558	inhibiting core fucosylation	1531:1558	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	13	33	theme	FUT8-based	1712:1721	arg1	strategy					1767:1774	a promising intervention strategy	1742:1774	a promising intervention strategy	1742:1774	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	13	33	theme	FUT8-based	1712:1721	arg1	treatment					1723:1731	FUT8-based treatment	1712:1731	FUT8-based treatment	1712:1731	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	10	34	theme	KW/BW	1310:1314	arg1	ACR					1326:1328	KW/BW and urine ACR	1310:1328	KW/BW and urine ACR	1310:1328	KW/BW and urine ACR were decreased significantly by inhibiting core fucosylation.
31623829	3	35	theme	interstitial	492:503	arg1	fibrosis					505:512	renal interstitial fibrosis	486:512	renal interstitial fibrosis of UUO murine models	486:533	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	6	36	theme	mouse	880:884	arg1	model					886:890	Then a new Fut8 mutation mouse model	855:890	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted	855:930	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted was constructed for diabetes induction.
31623829	4	37	dep	effects	661:667	arg1	the					646:648	the	646:648	the	646:648	This study aimed to clarify the protective effects and molecular mechanisms during the progress of DKD by inhibiting core fucosylation in vivo.
31623829	5	38	theme	-induced	824:831	arg1	model					848:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	METHODS Core fucosylation was examined in streptozotocin (STZ)-induced diabetic mouse model.
31623829	6	39	theme	Fut8	866:869	arg1	model					886:890	Then a new Fut8 mutation mouse model	855:890	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted	855:930	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted was constructed for diabetes induction.
31623829	12	40	theme	fucosylation	1547:1558	arg1	effects					1520:1526	The protective effects	1505:1526	The protective effects of inhibiting core fucosylation	1505:1558	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	9	41	theme	blood	1155:1159	arg1	glucose					1161:1167	fasting blood glucose	1147:1167	fasting blood glucose	1147:1167	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	3	42	theme	murine	521:526	arg1	models					528:533	UUO murine models	517:533	UUO murine models	517:533	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	9	43	dep	RESULTS	1125:1131	arg1	levels					1137:1142	The levels	1133:1142	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR)	1125:1265	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	2	44	theme	immune	389:394	arg1	regulation					396:405	immune regulation	389:405	immune regulation	389:405	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	1	45	theme	signaling	238:246	arg1	function					258:265	signaling receptors function	238:265	signaling receptors function	238:265	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	9	46	theme	hemoglobin	1179:1188	arg1	RESULTS					1125:1131	RESULTS The levels	1125:1142	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR)	1125:1265	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	6	47	theme	gene	916:919	arg1	exon					901:904	exon 7	901:906	exon 7 of Fut8 gene	901:919	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted was constructed for diabetes induction.
31623829	6	48	theme	mutation	871:878	arg1	model					886:890	Then a new Fut8 mutation mouse model	855:890	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted	855:930	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted was constructed for diabetes induction.
31623829	3	49	from	role	544:547	arg1	development					556:566	the development	552:566	the development of diabetic kidney disease (DKD)	552:599	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	2	50	theme	various	301:307	arg1	processes					320:328	various biological processes	301:328	various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation	301:405	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	50	theme	various	301:307	arg1	regulation					396:405	immune regulation	389:405	immune regulation	389:405	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	50	theme	various	301:307	arg1	apoptosis					358:366	apoptosis	358:366	apoptosis	358:366	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	50	theme	various	301:307	arg1	proliferation					343:355	cell proliferation	338:355	cell proliferation	338:355	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	2	50	theme	various	301:307	arg1	differentiation					369:383	differentiation	369:383	differentiation	369:383	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	1	51	gly	glycoproteins	208:220	arg1	glycoproteins					208:220	the N-linked type glycoproteins	190:220	the N-linked type glycoproteins	190:220	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	13	52	dep	CONCLUSIONS	1674:1684	arg1	indicate					1698:1705	indicate	1698:1705	indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD	1698:1805	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	8	53	theme	Renal	1018:1022	arg1	structure					1024:1032	Renal structure	1018:1032	Renal structure	1018:1032	Renal structure, fibrosis, and podocyte injury were assessed, and underlying mechanisms were investigated.
31623829	4	54	theme	molecular	673:681	arg1	mechanisms					683:692	molecular mechanisms	673:692	molecular mechanisms	673:692	This study aimed to clarify the protective effects and molecular mechanisms during the progress of DKD by inhibiting core fucosylation in vivo.
31623829	9	55	theme	urine	1233:1237	arg1	ACR					1262:1264	ACR	1262:1264	ACR	1262:1264	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	9	55	theme	urine	1233:1237	arg1	albumin-to-creatinine					1239:1259	urine albumin-to-creatinine	1233:1259	urine albumin-to-creatinine (ACR)	1233:1265	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	3	56	theme	disease	587:593	arg1	development					556:566	the development	552:566	the development of diabetic kidney disease (DKD)	552:599	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	7	57	theme	Metabolic	972:980	arg1	parameters					992:1001	Metabolic and renal parameters	972:1001	Metabolic and renal parameters	972:1001	Metabolic and renal parameters were measured.
31623829	1	58	theme	type	203:206	arg1	glycoproteins					208:220	the N-linked type glycoproteins	190:220	the N-linked type glycoproteins	190:220	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	6	59	theme	diabetes	952:959	arg1	induction					961:969	diabetes induction	952:969	diabetes induction	952:969	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted was constructed for diabetes induction.
31623829	13	60	theme	DKD	1803:1805	arg1	paradigm					1791:1798	therapeutic paradigm	1779:1798	therapeutic paradigm of DKD	1779:1805	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	12	61	theme	signal-regulated	1643:1658	arg1	ERK					1668:1670	extracellular signal-regulated kinase (ERK)	1629:1671	extracellular signal-regulated kinase (ERK)	1629:1671	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	0	62	theme	disease	70:76	arg1	progression					39:49	progression	39:49	progression of diabetic kidney disease	39:76	Inhibition of core fucosylation limits progression of diabetic kidney disease.
31623829	4	63	theme	DKD	717:719	arg1	effects					661:667	protective effects	650:667	protective effects	650:667	This study aimed to clarify the protective effects and molecular mechanisms during the progress of DKD by inhibiting core fucosylation in vivo.
31623829	4	63	theme	DKD	717:719	arg1	mechanisms					683:692	molecular mechanisms	673:692	molecular mechanisms	673:692	This study aimed to clarify the protective effects and molecular mechanisms during the progress of DKD by inhibiting core fucosylation in vivo.
31623829	8	64	theme	podocyte	1049:1056	arg1	injury					1058:1063	podocyte injury	1049:1063	podocyte injury	1049:1063	Renal structure, fibrosis, and podocyte injury were assessed, and underlying mechanisms were investigated.
31623829	13	65	theme	therapeutic	1779:1789	arg1	paradigm					1791:1798	therapeutic paradigm	1779:1798	therapeutic paradigm of DKD	1779:1805	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	3	66	theme	models	528:533	arg1	fibrosis					505:512	renal interstitial fibrosis	486:512	renal interstitial fibrosis of UUO murine models	486:533	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	5	67	theme	Core	770:773	arg1	fucosylation					775:786	METHODS Core fucosylation	762:786	METHODS Core fucosylation	762:786	METHODS Core fucosylation was examined in streptozotocin (STZ)-induced diabetic mouse model.
31623829	1	68	link	N-linked	194:201	arg1	glycoproteins					208:220	the N-linked type glycoproteins	190:220	the N-linked type glycoproteins	190:220	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	3	69	theme	renal	486:490	arg1	fibrosis					505:512	renal interstitial fibrosis	486:512	renal interstitial fibrosis of UUO murine models	486:533	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	5	70	theme	diabetic	833:840	arg1	model					848:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	streptozotocin (STZ)-induced diabetic mouse model	804:852	METHODS Core fucosylation was examined in streptozotocin (STZ)-induced diabetic mouse model.
31623829	1	71	theme	FUT8-mediated	90:102	arg1	fucosylation					109:120	BACKGROUND FUT8-mediated core fucosylation	79:120	BACKGROUND FUT8-mediated core fucosylation	79:120	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
31623829	3	72	theme	previous	412:419	arg1	studies					421:427	Our previous studies	408:427	Our previous studies	408:427	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	13	73	theme	promising	1744:1752	arg1	strategy					1767:1774	a promising intervention strategy	1742:1774	a promising intervention strategy	1742:1774	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	13	73	theme	promising	1744:1752	arg1	treatment					1723:1731	FUT8-based treatment	1712:1731	FUT8-based treatment	1712:1731	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	11	74	theme	core	1486:1489	arg1	fucosylation					1491:1502	core fucosylation	1486:1502	core fucosylation	1486:1502	The renal pathology, fibrosis, and podocyte injury were mitigated significantly by inhibiting core fucosylation.
31623829	0	75	theme	fucosylation	19:30	arg1	Inhibition					0:9	Inhibition	0:9	Inhibition of core fucosylation	0:30	Inhibition of core fucosylation limits progression of diabetic kidney disease.
31623829	8	76	theme	underlying	1084:1093	arg1	mechanisms					1095:1104	underlying mechanisms	1084:1104	underlying mechanisms	1084:1104	Renal structure, fibrosis, and podocyte injury were assessed, and underlying mechanisms were investigated.
31623829	3	77	theme	UUO	517:519	arg1	models					528:533	UUO murine models	517:533	UUO murine models	517:533	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	3	78	theme	inhibiting	447:456	arg1	fucosylation					463:474	inhibiting core fucosylation	447:474	inhibiting core fucosylation	447:474	Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear.
31623829	0	79	theme	diabetic	54:61	arg1	disease					70:76	diabetic kidney disease	54:76	diabetic kidney disease	54:76	Inhibition of core fucosylation limits progression of diabetic kidney disease.
31623829	12	80	theme	core	1542:1545	arg1	fucosylation					1547:1558	inhibiting core fucosylation	1531:1558	inhibiting core fucosylation	1531:1558	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	9	81	theme	fasting	1147:1153	arg1	glucose					1161:1167	fasting blood glucose	1147:1167	fasting blood glucose	1147:1167	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	13	82	from	strategy	1767:1774	arg1	paradigm					1791:1798	therapeutic paradigm	1779:1798	therapeutic paradigm of DKD	1779:1805	CONCLUSIONS Our results indicate that FUT8-based treatment might be a promising intervention strategy in therapeutic paradigm of DKD.
31623829	6	83	theme	new	862:864	arg1	model					886:890	Then a new Fut8 mutation mouse model	855:890	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted	855:930	Then a new Fut8 mutation mouse model in which exon 7 of Fut8 gene is deleted was constructed for diabetes induction.
31623829	9	84	theme	glycated	1170:1177	arg1	hemoglobin					1179:1188	glycated hemoglobin	1170:1188	glycated hemoglobin	1170:1188	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	9	85	theme	glucose	1161:1167	arg1	RESULTS					1125:1131	RESULTS The levels	1125:1142	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR)	1125:1265	RESULTS The levels of fasting blood glucose, glycated hemoglobin, kidney-weight-to- body-weight (KW/BW) and urine albumin-to-creatinine (ACR) were increased at 16 weeks post injection.
31623829	2	86	theme	cell	338:341	arg1	proliferation					343:355	cell proliferation	338:355	cell proliferation	338:355	Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation.
31623829	12	87	theme	protective	1509:1518	arg1	effects					1520:1526	The protective effects	1505:1526	The protective effects of inhibiting core fucosylation	1505:1558	The protective effects of inhibiting core fucosylation were mediated by downregulated of the phosphorylation of Smad2/3 and extracellular signal-regulated kinase (ERK).
31623829	10	88	theme	core	1373:1376	arg1	fucosylation					1378:1389	core fucosylation	1373:1389	core fucosylation	1373:1389	KW/BW and urine ACR were decreased significantly by inhibiting core fucosylation.
31623829	1	89	theme	receptors	248:256	arg1	function					258:265	signaling receptors function	238:265	signaling receptors function	238:265	BACKGROUND FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function.
30355496	7	0	theme	preferred	1215:1223	arg1	components					1225:1234	preferred components	1215:1234	preferred components of AIDS vaccines	1215:1251	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	5	1	theme	most	812:815	arg1	holes					824:828	most glycan holes	812:828	most glycan holes present at transmission	812:852	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	7	2	theme	glycan-shielded	1057:1071	arg1	viruses					1073:1079	completely glycan-shielded viruses	1046:1079	completely glycan-shielded viruses	1046:1079	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	2	3	theme	antibodies	298:307	arg1	targets					258:264	targets	258:264	targets of vaccine-induced neutralizing antibodies that lack breadth	258:325	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	4	4	theme	followed	619:626	arg1	individuals					628:638	12 longitudinally followed individuals	601:638	12 longitudinally followed individuals	601:638	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	2	5	from	Strain-specific	196:210	arg1	holes					244:248	this shield (glycan holes)	224:249	this shield (glycan holes)	224:249	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	0	6	from	Transmission	48:59	arg1	HIV-1					16:20	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	0	6	from	Transmission	48:59	arg1	Envelope					22:29	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	0	6	from	Transmission	48:59	arg1	at					45:46	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	0	6	from	Transmission	48:59	arg1	Glycan					31:36	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	7	7	theme	accelerated	1102:1112	arg1	development					1137:1147	accelerated neutralization breadth development	1102:1147	accelerated neutralization breadth development	1102:1147	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	7	8	theme	vaccines	1244:1251	arg1	components					1225:1234	preferred components	1215:1234	preferred components of AIDS vaccines	1215:1251	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	2	9	theme	neutralizing	285:296	arg1	antibodies					298:307	vaccine-induced neutralizing antibodies	269:307	vaccine-induced neutralizing antibodies that lack breadth	269:325	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	4	10	theme	breadth	761:767	arg1	development					723:733	development	723:733	development of greater neutralization breadth	723:767	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	4	11	theme	neutralization	746:759	arg1	breadth					761:767	greater neutralization breadth	738:767	greater neutralization breadth	738:767	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	7	12	theme	glycan	1193:1198	arg1	shields					1200:1206	intact glycan shields	1186:1206	intact glycan shields	1186:1206	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	5	13	theme	hole-targeting	878:891	arg1	antibodies					906:915	hole-targeting neutralizing antibodies	878:915	hole-targeting neutralizing antibodies	878:915	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	2	14	theme	vaccine-induced	269:283	arg1	antibodies					298:307	vaccine-induced neutralizing antibodies	269:307	vaccine-induced neutralizing antibodies that lack breadth	269:325	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	4	15	theme	intact	685:690	arg1	shields					699:705	more intact glycan shields	680:705	more intact glycan shields	680:705	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	3	16	theme	glycan	364:369	arg1	holes					371:375	glycan holes	364:375	glycan holes	364:375	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	5	17	from	transmission	841:852	arg1	present					830:836	present	830:836	present	830:836	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	5	18	theme	glycan	817:822	arg1	holes					824:828	most glycan holes	812:828	most glycan holes present at transmission	812:852	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	3	19	theme	most	553:556	arg1	viruses					566:572	most M-group viruses	553:572	most M-group viruses	553:572	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	2	20	from	holes	244:248	arg1	Strain-specific					196:210	Strain-specific	196:210	Strain-specific	196:210	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	1	21	theme	antibody	174:181	arg1	recognition					183:193	antibody recognition	174:193	antibody recognition	174:193	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
30355496	3	22	theme	neutralization	381:394	arg1	breadth					396:402	neutralization breadth	381:402	neutralization breadth	381:402	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	0	23	theme	Neutralization	72:85	arg1	Breadth					87:93	Neutralization Breadth	72:93	Neutralization Breadth	72:93	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	3	24	theme	HIV-1	407:411	arg1	infection					413:421	HIV-1 infection	407:421	HIV-1 infection	407:421	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	7	25	theme	intact	1186:1191	arg1	shields					1200:1206	intact glycan shields	1186:1206	intact glycan shields	1186:1206	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	1	26	theme	arranged	104:111	arg1	glycans					122:128	Densely arranged N-linked glycans	96:128	Densely arranged N-linked glycans	96:128	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
30355496	3	27	theme	sequence-	439:447	arg1	approach					469:476	a sequence- and structure-based approach	437:476	a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses	437:572	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	0	28	theme	Envelope	22:29	arg1	Transmission					48:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	7	29	theme	Env	1166:1168	arg1	immunogens					1170:1179	Env immunogens	1166:1179	Env immunogens with intact glycan shields	1166:1206	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	5	30	attach	present	830:836	arg1	transmission					841:852	transmission	841:852	transmission	841:852	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	5	30	attach	present	830:836	arg2	holes					824:828	most glycan holes	812:828	most glycan holes present at transmission	812:852	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	1	31	theme	N-linked	113:120	arg1	glycans					122:128	Densely arranged N-linked glycans	96:128	Densely arranged N-linked glycans	96:128	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
30355496	4	32	theme	transmitted	655:665	arg1	viruses					667:673	transmitted viruses	655:673	transmitted viruses with more intact glycan shields	655:705	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	0	33	theme	HIV-1	16:20	arg1	Transmission					48:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	3	34	theme	glycan	490:495	arg1	holes					497:501	glycan holes	490:501	glycan holes for individual Env sequences that are shielded in most M-group viruses	490:572	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	0	35	theme	Shield	38:43	arg1	Transmission					48:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	4	36	theme	greater	738:744	arg1	breadth					761:767	greater neutralization breadth	738:767	greater neutralization breadth	738:767	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	6	37	theme	hole	925:928	arg1	filling					930:936	Glycan hole filling	918:936	Glycan hole filling	918:936	Glycan hole filling generally preceded the time to first detectable breadth, although time intervals varied across hosts.
30355496	5	38	theme	glycan	786:791	arg1	acquisition					793:803	glycan acquisition	786:803	glycan acquisition	786:803	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	4	39	theme	glycan	692:697	arg1	shields					699:705	more intact glycan shields	680:705	more intact glycan shields	680:705	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	5	40	theme	neutralizing	893:904	arg1	antibodies					906:915	hole-targeting neutralizing antibodies	878:915	hole-targeting neutralizing antibodies	878:915	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	0	41	theme	Glycan	31:36	arg1	Transmission					48:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	6	42	theme	Glycan	918:923	arg1	filling					930:936	Glycan hole filling	918:936	Glycan hole filling	918:936	Glycan hole filling generally preceded the time to first detectable breadth, although time intervals varied across hosts.
30355496	2	43	theme	glycan	237:242	arg1	holes					244:248	this shield (glycan holes)	224:249	this shield (glycan holes)	224:249	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	7	44	with	immunogens	1170:1179	arg1	shields					1200:1206	intact glycan shields	1186:1206	intact glycan shields	1186:1206	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	0	45	theme	Transmission	48:59	arg1	Completeness					0:11	Completeness	0:11	Completeness of HIV-1 Envelope Glycan Shield at Transmission	0:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	5	46	from	antibodies	906:915	arg1	escape					866:871	escape	866:871	escape from hole-targeting neutralizing antibodies	866:915	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	3	47	theme	individual	507:516	arg1	sequences					522:530	individual Env sequences	507:530	individual Env sequences that are shielded in most M-group viruses	507:572	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	0	48	theme	at	45:46	arg1	Transmission					48:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	HIV-1 Envelope Glycan Shield at Transmission	16:59	Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.
30355496	6	49	theme	time	1004:1007	arg1	intervals					1009:1017	time intervals	1004:1017	time intervals	1004:1017	Glycan hole filling generally preceded the time to first detectable breadth, although time intervals varied across hosts.
30355496	2	50	theme	shield	229:234	arg1	holes					244:248	this shield (glycan holes)	224:249	this shield (glycan holes)	224:249	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	3	51	theme	Env	518:520	arg1	sequences					522:530	individual Env sequences	507:530	individual Env sequences that are shielded in most M-group viruses	507:572	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	7	52	theme	neutralization	1114:1127	arg1	development					1137:1147	accelerated neutralization breadth development	1102:1147	accelerated neutralization breadth development	1102:1147	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	4	53	with	viruses	667:673	arg1	shields					699:705	more intact glycan shields	680:705	more intact glycan shields	680:705	Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth.
30355496	7	54	theme	AIDS	1239:1242	arg1	vaccines					1244:1251	AIDS vaccines	1239:1251	AIDS vaccines	1239:1251	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	1	55	theme	HIV-1	141:145	arg1	trimer					162:167	the HIV-1 envelope (Env) trimer	137:167	the HIV-1 envelope (Env) trimer from antibody recognition	137:193	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
30355496	7	56	theme	breadth	1129:1135	arg1	development					1137:1147	accelerated neutralization breadth development	1102:1147	accelerated neutralization breadth development	1102:1147	Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
30355496	3	57	theme	M-group	558:564	arg1	viruses					566:572	most M-group viruses	553:572	most M-group viruses	553:572	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	1	58	from	recognition	183:193	arg1	trimer					162:167	the HIV-1 envelope (Env) trimer	137:167	the HIV-1 envelope (Env) trimer from antibody recognition	137:193	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
30355496	1	59	theme	envelope	147:154	arg1	trimer					162:167	the HIV-1 envelope (Env) trimer	137:167	the HIV-1 envelope (Env) trimer from antibody recognition	137:193	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
30355496	2	60	dep	Strain-specific	196:210	arg1	breaches					212:219	breaches	212:219	breaches	212:219	Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth.
30355496	1	61	link	N-linked	113:120	arg1	glycans					122:128	Densely arranged N-linked glycans	96:128	Densely arranged N-linked glycans	96:128	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
30355496	3	62	from	interplay	346:354	arg1	infection					413:421	HIV-1 infection	407:421	HIV-1 infection	407:421	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	3	63	theme	structure-based	453:467	arg1	approach					469:476	a sequence- and structure-based approach	437:476	a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses	437:572	To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses.
30355496	5	64	theme	present	830:836	arg1	holes					824:828	most glycan holes	812:828	most glycan holes present at transmission	812:852	Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies.
30355496	1	65	theme	Env	157:159	arg1	trimer					162:167	the HIV-1 envelope (Env) trimer	137:167	the HIV-1 envelope (Env) trimer from antibody recognition	137:193	Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition.
27670784	1	0	theme	endoplasmic	317:327	arg1	reticulum					329:337	endoplasmic reticulum	317:337	endoplasmic reticulum membrane-associated glycosyltransferases	317:378	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	5	1	theme	high	888:891	arg1	yield					893:897	high yield	888:897	high yield	888:897	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	1	2	theme	DLO	243:245	arg1	Glc3Man9GlcNAc2-PP-Dol					259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	1	2	theme	DLO	243:245	arg1	precursor					248:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	10	3	from	effect	1701:1706	arg1	activity					1740:1747	enzyme activity	1733:1747	enzyme activity	1733:1747	Furthermore, the effect of ALG1-CDG mutations on enzyme activity was also measured.
27670784	1	4	theme	reticulum	329:337	arg1	glycosyltransferases					359:378	endoplasmic reticulum membrane-associated glycosyltransferases	317:378	endoplasmic reticulum membrane-associated glycosyltransferases	317:378	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	9	5	theme	nucleotide	1660:1669	arg1	donor					1677:1681	its nucleotide sugar donor	1656:1681	its nucleotide sugar donor	1656:1681	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	6	theme	apparent	1559:1566	arg1	Km					1568:1569	the apparent Km	1555:1569	the apparent Km	1555:1569	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	7	theme	biochemical	1498:1508	arg1	characteristics					1510:1524	its biochemical characteristics	1494:1524	its biochemical characteristics	1494:1524	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	8	theme	optimal	1601:1607	arg1	conditions					1609:1618	optimal conditions	1601:1618	optimal conditions of activity	1601:1630	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	1	9	theme	membrane-associated	339:357	arg1	glycosyltransferases					359:378	endoplasmic reticulum membrane-associated glycosyltransferases	317:378	endoplasmic reticulum membrane-associated glycosyltransferases	317:378	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	9	10	theme	sugar	1671:1675	arg1	donor					1677:1681	its nucleotide sugar donor	1656:1681	its nucleotide sugar donor	1656:1681	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	11	theme	activity	1623:1630	arg1	Km					1568:1569	the apparent Km	1555:1569	the apparent Km	1555:1569	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	11	theme	activity	1623:1630	arg1	values					1580:1585	Vmax values	1575:1585	Vmax values	1575:1585	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	11	theme	activity	1623:1630	arg1	specificity					1641:1651	the specificity	1637:1651	the specificity of its nucleotide sugar donor	1637:1681	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	11	theme	activity	1623:1630	arg1	conditions					1609:1618	optimal conditions	1601:1618	optimal conditions of activity	1601:1630	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	12	theme	Vmax	1575:1578	arg1	values					1580:1585	Vmax values	1575:1585	Vmax values	1575:1585	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	1	13	theme	precursor	248:256	arg1	synthesis					193:201	a stepwise synthesis	182:201	a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases	182:378	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	0	14	theme	key	75:77	arg1	enzyme					79:84	a key enzyme	73:84	a key enzyme involved in protein N-glycosylation	73:120	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	0	14	theme	key	75:77	arg1	beta-1					33:38	yeast Alg1 beta-1	22:38	yeast Alg1 beta-1	22:38	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	1	15	theme	glycosyltransferases	359:378	arg1	series					307:312	a series	305:312	a series of endoplasmic reticulum membrane-associated glycosyltransferases	305:378	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	9	16	theme	donor	1677:1681	arg1	Km					1568:1569	the apparent Km	1555:1569	the apparent Km	1555:1569	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	16	theme	donor	1677:1681	arg1	values					1580:1585	Vmax values	1575:1585	Vmax values	1575:1585	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	16	theme	donor	1677:1681	arg1	specificity					1641:1651	the specificity	1637:1651	the specificity of its nucleotide sugar donor	1637:1681	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	9	16	theme	donor	1677:1681	arg1	conditions					1609:1618	optimal conditions	1601:1618	optimal conditions of activity	1601:1630	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	5	17	from	Alg1	880:883	arg1	yield					893:897	high yield	888:897	high yield	888:897	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	7	18	with	combination	1145:1155	arg1	technology					1168:1177	LC-MS technology	1162:1177	LC-MS technology	1162:1177	In combination with LC-MS technology, we established a novel assay to accurately measure Alg1 enzyme activity.
27670784	10	19	theme	mutations	1720:1728	arg1	effect					1701:1706	the effect	1697:1706	the effect of ALG1-CDG mutations on enzyme activity	1697:1747	Furthermore, the effect of ALG1-CDG mutations on enzyme activity was also measured.
27670784	6	20	theme	HP	1114:1115	arg1	chromatography					1126:1139	HisTrap HP affinity chromatography	1106:1139	HisTrap HP affinity chromatography	1106:1139	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	2	21	theme	core	526:529	arg1	Man1GlcNAc2-PP-Dol					545:562	a core trisaccharide Man1GlcNAc2-PP-Dol	524:562	a core trisaccharide Man1GlcNAc2-PP-Dol	524:562	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	6	22	dep	METHODS	995:1001	arg1	protein					1048:1054	N-terminally truncated yeast His-tagged Alg1 protein	1003:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein	995:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	8	23	link	dolichol-linked	1293:1307	arg1	phytanyl-pyrophosphoryl-α-N					1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	23	link	dolichol-linked	1293:1307	arg1	acceptor					1413:1420	the acceptor	1409:1420	the acceptor for the β-1, 4 mannosyl transfer reaction	1409:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	23	link	dolichol-linked	1293:1307	arg1	analogue					1325:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	23	link	dolichol-linked	1293:1307	arg1	N'-diacetylchitobioside					1364:1386	N'-diacetylchitobioside	1364:1386	N'-diacetylchitobioside (PPGn2)	1364:1394	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	5	24	theme	β-1	958:960	arg1	activity					985:992	its β-1, 4 mannosyltransferase activity	954:992	activity	985:992	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	1	25	theme	-linked	148:154	arg1	glycosylation					156:168	BACKGROUND Asparagine (N)-linked glycosylation	123:168	BACKGROUND Asparagine (N)-linked glycosylation	123:168	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	7	26	theme	novel	1197:1201	arg1	assay					1203:1207	a novel assay	1195:1207	a novel assay to accurately measure Alg1 enzyme activity	1195:1250	In combination with LC-MS technology, we established a novel assay to accurately measure Alg1 enzyme activity.
27670784	5	27	theme	spectral	911:918	arg1	approach					920:927	a mass spectral approach	904:927	a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity	904:992	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	11	28	theme	efficient	1811:1819	arg1	method					1821:1826	an efficient method	1808:1826	an efficient method for production of Alg1	1808:1849	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	1	29	link	-linked	148:154	arg1	glycosylation					156:168	BACKGROUND Asparagine (N)-linked glycosylation	123:168	BACKGROUND Asparagine (N)-linked glycosylation	123:168	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	4	30	theme	expression	750:759	arg1	level					761:765	its low expression level	742:765	its low expression level	742:765	Alg1 is difficult to purify because of its low expression level and as a consequence, has not been well studied biochemically.
27670784	2	31	theme	asparagine-linked	393:409	arg1	glycosylation					411:423	asparagine-linked glycosylation 1	393:425	asparagine-linked glycosylation 1	393:425	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	2	31	theme	asparagine-linked	393:409	arg1	ALG1					387:390	Yeast ALG1	381:390	Yeast ALG1 (asparagine-linked glycosylation 1)	381:426	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	0	32	theme	Quantitative	0:11	arg1	study					13:17	Quantitative study	0:17	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.	0:121	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	7	33	theme	LC-MS	1162:1166	arg1	technology					1168:1177	LC-MS technology	1162:1177	LC-MS technology	1162:1177	In combination with LC-MS technology, we established a novel assay to accurately measure Alg1 enzyme activity.
27670784	4	34	theme	low	746:748	arg1	level					761:765	its low expression level	742:765	its low expression level	742:765	Alg1 is difficult to purify because of its low expression level and as a consequence, has not been well studied biochemically.
27670784	5	35	theme	recombinant	868:878	arg1	Alg1					880:883	recombinant Alg1	868:883	recombinant Alg1 in high yield	868:897	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	0	36	theme	yeast	22:26	arg1	beta-1					33:38	yeast Alg1 beta-1	22:38	yeast Alg1 beta-1	22:38	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	0	36	theme	yeast	22:26	arg1	activity					63:70	4 mannosyltransferase activity	41:70	4 mannosyltransferase activity	41:70	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	0	36	theme	yeast	22:26	arg1	enzyme					79:84	a key enzyme	73:84	a key enzyme involved in protein N-glycosylation	73:120	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	8	37	theme	oligosaccharide	1309:1323	arg1	phytanyl-pyrophosphoryl-α-N					1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	37	theme	oligosaccharide	1309:1323	arg1	acceptor					1413:1420	the acceptor	1409:1420	the acceptor for the β-1, 4 mannosyl transfer reaction	1409:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	37	theme	oligosaccharide	1309:1323	arg1	analogue					1325:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	37	theme	oligosaccharide	1309:1323	arg1	N'-diacetylchitobioside					1364:1386	N'-diacetylchitobioside	1364:1386	N'-diacetylchitobioside (PPGn2)	1364:1394	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	1	38	link	dolichol-linked	210:224	arg1	Glc3Man9GlcNAc2-PP-Dol					259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	1	38	link	dolichol-linked	210:224	arg1	precursor					248:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	11	39	theme	new	1857:1859	arg1	assay					1883:1887	a new MS-based quantitative assay	1855:1887	a new MS-based quantitative assay of its activity	1855:1903	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	9	40	theme	purified	1479:1486	arg1	Alg1					1488:1491	purified Alg1	1479:1491	purified Alg1	1479:1491	RESULTS Using purified Alg1, its biochemical characteristics were investigated, including the apparent Km and Vmax values for acceptor, optimal conditions of activity, and the specificity of its nucleotide sugar donor.
27670784	11	41	theme	GENERAL	1768:1774	arg1	SIGNIFICANCE					1776:1787	GENERAL SIGNIFICANCE	1768:1787	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.	1768:1904	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	0	42	theme	protein	98:104	arg1	N-glycosylation					106:120	protein N-glycosylation	98:120	protein N-glycosylation	98:120	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	2	43	link	asparagine-linked	393:409	arg1	glycosylation					411:423	asparagine-linked glycosylation 1	393:425	asparagine-linked glycosylation 1	393:425	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	2	43	link	asparagine-linked	393:409	arg1	ALG1					387:390	Yeast ALG1	381:390	Yeast ALG1 (asparagine-linked glycosylation 1)	381:426	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	3	44	theme	yeast	587:591	arg1	viability					593:601	yeast viability	587:601	yeast viability	587:601	ALG1 is essential for yeast viability, and in humans mutations in the ALG1 cause congenital disorders of glycosylation known as ALG1-CDG.
27670784	1	45	theme	stepwise	184:191	arg1	synthesis					193:201	a stepwise synthesis	182:201	a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases	182:378	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	0	46	theme	beta-1	33:38	arg1	study					13:17	Quantitative study	0:17	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.	0:121	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	10	47	theme	ALG1-CDG	1711:1718	arg1	mutations					1720:1728	ALG1-CDG mutations	1711:1728	ALG1-CDG mutations	1711:1728	Furthermore, the effect of ALG1-CDG mutations on enzyme activity was also measured.
27670784	11	48	theme	MS-based	1861:1868	arg1	assay					1883:1887	a new MS-based quantitative assay	1855:1887	a new MS-based quantitative assay of its activity	1855:1903	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	3	49	theme	glycosylation	670:682	arg1	disorders					657:665	congenital disorders	646:665	congenital disorders of glycosylation known as ALG1-CDG	646:700	ALG1 is essential for yeast viability, and in humans mutations in the ALG1 cause congenital disorders of glycosylation known as ALG1-CDG.
27670784	3	50	from	mutations	618:626	arg1	ALG1					635:638	the ALG1	631:638	the ALG1	631:638	ALG1 is essential for yeast viability, and in humans mutations in the ALG1 cause congenital disorders of glycosylation known as ALG1-CDG.
27670784	6	51	theme	Alg1	1043:1046	arg1	protein					1048:1054	N-terminally truncated yeast His-tagged Alg1 protein	1003:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein	995:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	0	52	theme	Alg1	28:31	arg1	beta-1					33:38	yeast Alg1 beta-1	22:38	yeast Alg1 beta-1	22:38	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	0	52	theme	Alg1	28:31	arg1	activity					63:70	4 mannosyltransferase activity	41:70	4 mannosyltransferase activity	41:70	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	0	52	theme	Alg1	28:31	arg1	enzyme					79:84	a key enzyme	73:84	a key enzyme involved in protein N-glycosylation	73:120	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	11	53	theme	Alg1	1846:1849	arg1	production					1832:1841	production	1832:1841	production of Alg1	1832:1849	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	2	54	theme	first	479:483	arg1	mannose					485:491	the first mannose	475:491	the first mannose onto GlcNAc2-PP-Dol	475:511	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	3	55	theme	congenital	646:655	arg1	disorders					657:665	congenital disorders	646:665	congenital disorders of glycosylation known as ALG1-CDG	646:700	ALG1 is essential for yeast viability, and in humans mutations in the ALG1 cause congenital disorders of glycosylation known as ALG1-CDG.
27670784	5	56	theme	new	847:849	arg1	method					851:856	a new method	845:856	a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity	845:992	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	7	57	theme	enzyme	1236:1241	arg1	activity					1243:1250	Alg1 enzyme activity	1231:1250	Alg1 enzyme activity	1231:1250	In combination with LC-MS technology, we established a novel assay to accurately measure Alg1 enzyme activity.
27670784	8	58	theme	β-1	1430:1432	arg1	reaction					1455:1462	the β-1, 4 mannosyl transfer reaction	1426:1462	reaction	1455:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	59	theme	dolichol-linked	1293:1307	arg1	phytanyl-pyrophosphoryl-α-N					1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	59	theme	dolichol-linked	1293:1307	arg1	acceptor					1413:1420	the acceptor	1409:1420	the acceptor for the β-1, 4 mannosyl transfer reaction	1409:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	59	theme	dolichol-linked	1293:1307	arg1	analogue					1325:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	59	theme	dolichol-linked	1293:1307	arg1	N'-diacetylchitobioside					1364:1386	N'-diacetylchitobioside	1364:1386	N'-diacetylchitobioside (PPGn2)	1364:1394	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	10	60	theme	enzyme	1733:1738	arg1	activity					1740:1747	enzyme activity	1733:1747	enzyme activity	1733:1747	Furthermore, the effect of ALG1-CDG mutations on enzyme activity was also measured.
27670784	11	61	theme	activity	1896:1903	arg1	method					1821:1826	an efficient method	1808:1826	an efficient method for production of Alg1	1808:1849	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	11	61	theme	activity	1896:1903	arg1	assay					1883:1887	a new MS-based quantitative assay	1855:1887	a new MS-based quantitative assay of its activity	1855:1903	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	11	62	dep	SIGNIFICANCE	1776:1787	arg1	provides					1799:1806	provides	1799:1806	provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity	1799:1903	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	8	63	theme	synthesized	1281:1291	arg1	phytanyl-pyrophosphoryl-α-N					1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	63	theme	synthesized	1281:1291	arg1	acceptor					1413:1420	the acceptor	1409:1420	the acceptor for the β-1, 4 mannosyl transfer reaction	1409:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	63	theme	synthesized	1281:1291	arg1	analogue					1325:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	63	theme	synthesized	1281:1291	arg1	N'-diacetylchitobioside					1364:1386	N'-diacetylchitobioside	1364:1386	N'-diacetylchitobioside (PPGn2)	1364:1394	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	11	64	theme	quantitative	1870:1881	arg1	assay					1883:1887	a new MS-based quantitative assay	1855:1887	a new MS-based quantitative assay of its activity	1855:1903	GENERAL SIGNIFICANCE This work provides an efficient method for production of Alg1 and a new MS-based quantitative assay of its activity.
27670784	6	65	theme	truncated	1016:1024	arg1	protein					1048:1054	N-terminally truncated yeast His-tagged Alg1 protein	1003:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein	995:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	6	66	theme	affinity	1117:1124	arg1	chromatography					1126:1139	HisTrap HP affinity chromatography	1106:1139	HisTrap HP affinity chromatography	1106:1139	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	6	67	theme	yeast	1026:1030	arg1	protein					1048:1054	N-terminally truncated yeast His-tagged Alg1 protein	1003:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein	995:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	5	68	theme	mannosyltransferase	965:983	arg1	activity					985:992	its β-1, 4 mannosyltransferase activity	954:992	activity	985:992	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	8	69	used	used	1401:1404	arg2	N'-diacetylchitobioside					1364:1386	N'-diacetylchitobioside	1364:1386	N'-diacetylchitobioside (PPGn2)	1364:1394	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	69	used	used	1401:1404	arg2	acceptor					1413:1420	the acceptor	1409:1420	the acceptor for the β-1, 4 mannosyl transfer reaction	1409:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	69	used	used	1401:1404	arg2	phytanyl-pyrophosphoryl-α-N					1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	phytanyl-pyrophosphoryl-α-N	1335:1361	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	8	69	used	used	1401:1404	arg2	analogue					1325:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	a chemically synthesized dolichol-linked oligosaccharide analogue	1268:1332	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	5	70	theme	mass	906:909	arg1	approach					920:927	a mass spectral approach	904:927	a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity	904:992	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	1	71	theme	dolichol-linked	210:224	arg1	Glc3Man9GlcNAc2-PP-Dol					259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	1	71	theme	dolichol-linked	210:224	arg1	precursor					248:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	7	72	theme	Alg1	1231:1234	arg1	activity					1243:1250	Alg1 enzyme activity	1231:1250	Alg1 enzyme activity	1231:1250	In combination with LC-MS technology, we established a novel assay to accurately measure Alg1 enzyme activity.
27670784	6	73	theme	His-tagged	1032:1041	arg1	protein					1048:1054	N-terminally truncated yeast His-tagged Alg1 protein	1003:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein	995:1054	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	8	74	theme	transfer	1446:1453	arg1	reaction					1455:1462	the β-1, 4 mannosyl transfer reaction	1426:1462	reaction	1455:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	6	75	theme	HisTrap	1106:1112	arg1	chromatography					1126:1139	HisTrap HP affinity chromatography	1106:1139	HisTrap HP affinity chromatography	1106:1139	METHODS N-terminally truncated yeast His-tagged Alg1 protein was expressed in Escherichia coli and purified by HisTrap HP affinity chromatography.
27670784	5	76	from	approach	920:927	arg1	yield					893:897	high yield	888:897	high yield	888:897	Here we report a new method to purify recombinant Alg1 in high yield, and a mass spectral approach for accurately measuring its β-1, 4 mannosyltransferase activity.
27670784	1	77	theme	oligosaccharide	226:240	arg1	Glc3Man9GlcNAc2-PP-Dol					259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	Glc3Man9GlcNAc2-PP-Dol	259:280	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	1	77	theme	oligosaccharide	226:240	arg1	precursor					248:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	the dolichol-linked oligosaccharide (DLO) precursor	206:256	BACKGROUND Asparagine (N)-linked glycosylation begins with a stepwise synthesis of the dolichol-linked oligosaccharide (DLO) precursor, Glc3Man9GlcNAc2-PP-Dol, which is catalyzed by a series of endoplasmic reticulum membrane-associated glycosyltransferases.
27670784	0	78	theme	mannosyltransferase	43:61	arg1	beta-1					33:38	yeast Alg1 beta-1	22:38	yeast Alg1 beta-1	22:38	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	0	78	theme	mannosyltransferase	43:61	arg1	activity					63:70	4 mannosyltransferase activity	41:70	4 mannosyltransferase activity	41:70	Quantitative study of yeast Alg1 beta-1, 4 mannosyltransferase activity, a key enzyme involved in protein N-glycosylation.
27670784	8	79	theme	mannosyl	1437:1444	arg1	reaction					1455:1462	the β-1, 4 mannosyl transfer reaction	1426:1462	reaction	1455:1462	In this assay, a chemically synthesized dolichol-linked oligosaccharide analogue, phytanyl-pyrophosphoryl-α-N, N'-diacetylchitobioside (PPGn2), was used as the acceptor for the β-1, 4 mannosyl transfer reaction.
27670784	2	80	theme	Yeast	381:385	arg1	glycosylation					411:423	asparagine-linked glycosylation 1	393:425	asparagine-linked glycosylation 1	393:425	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	2	80	theme	Yeast	381:385	arg1	β-1					438:440	a β-1	436:440	a β-1	436:440	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	2	80	theme	Yeast	381:385	arg1	ALG1					387:390	Yeast ALG1	381:390	Yeast ALG1 (asparagine-linked glycosylation 1)	381:426	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
27670784	2	81	theme	trisaccharide	531:543	arg1	Man1GlcNAc2-PP-Dol					545:562	a core trisaccharide Man1GlcNAc2-PP-Dol	524:562	a core trisaccharide Man1GlcNAc2-PP-Dol	524:562	Yeast ALG1 (asparagine-linked glycosylation 1) encodes a β-1, 4 mannosyltransferase that adds the first mannose onto GlcNAc2-PP-Dol to produce a core trisaccharide Man1GlcNAc2-PP-Dol.
31918287	12	0	theme	protein	1706:1712	arg1	carriers					1714:1721	multiple protein carriers	1697:1721	multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS	1697:1798	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	13	1	theme	macrophage	1870:1879	arg1	apoptosis					1881:1889	macrophage apoptosis	1870:1889	macrophage apoptosis	1870:1889	Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.
31918287	4	2	theme	coli	569:572	arg1	LPS					595:597	LPS	595:597	LPS	595:597	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	4	2	theme	coli	569:572	arg1	lipopolysaccharides					574:592	E. coli lipopolysaccharides	566:592	E. coli lipopolysaccharides (LPS)	566:598	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	10	3	theme	signaling	1494:1502	arg1	pathway					1504:1510	NF-κB signaling pathway	1488:1510	NF-κB signaling pathway	1488:1510	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	8	4	theme	expression	1172:1181	arg1	effect					1152:1157	the effect	1148:1157	the effect of increased expression of Siglec-E ligands	1148:1201	MAECs induced by LPS were co-cultured with macrophages and the effect of increased expression of Siglec-E ligands analyzed.
31918287	12	5	theme	malignant	1644:1652	arg1	tumors-1					1660:1667	malignant brain tumors-1	1644:1667	malignant brain tumors-1	1644:1667	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	8	6	theme	Siglec-E	1186:1193	arg1	ligands					1195:1201	Siglec-E ligands	1186:1201	Siglec-E ligands	1186:1201	MAECs induced by LPS were co-cultured with macrophages and the effect of increased expression of Siglec-E ligands analyzed.
31918287	14	7	theme	vascular	2125:2132	arg1	inflammation					2134:2145	LPS-induced vascular inflammation	2113:2145	LPS-induced vascular inflammation	2113:2145	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	7	8	theme	Siglec-E	1023:1030	arg1	ligands					1032:1038	Siglec-E ligands	1023:1038	Siglec-E ligands induced by LPS with or without NF-κB inhibitors	1023:1086	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	1	9	theme	cell	170:173	arg1	receptor					183:190	an immunosuppressive cell surface receptor	149:190	an immunosuppressive cell surface receptor	149:190	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	1	9	theme	cell	170:173	arg1	AIMS					93:96	AIMS Siglec-E	93:105	AIMS Siglec-E	93:105	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	4	10	theme	mouse	603:607	arg1	aorta					609:613	mouse aorta	603:613	mouse aorta	603:613	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	10	11	theme	dependent	1512:1520	arg1	manner					1522:1527	an NF-κB signaling pathway dependent manner	1485:1527	an NF-κB signaling pathway dependent manner	1485:1527	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	4	12	theme	present	419:425	arg1	study					427:431	the present study	415:431	the present study	415:431	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	5	13	theme	ligands	692:698	arg1	distribution					628:639	distribution	628:639	distribution	628:639	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	5	13	theme	ligands	692:698	arg1	size					652:655	molecular size	642:655	molecular size	642:655	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	5	13	theme	ligands	692:698	arg1	class					674:678	glycoprotein class	661:678	glycoprotein class	661:678	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	6	14	theme	inhibitor	887:895	arg1	administration					897:910	NF-κB inhibitor administration	881:910	NF-κB inhibitor administration	881:910	In vivo, the expression of Siglec-E ligands was detected after LPS treatment, with or without NF-κB inhibitor administration.
31918287	7	15	theme	endothelial	953:963	arg1	cells					965:969	cultured primary mouse aortic endothelial cells	923:969	cultured primary mouse aortic endothelial cells (MAECs)	923:977	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	7	15	theme	endothelial	953:963	arg1	MAECs					972:976	MAECs	972:976	MAECs	972:976	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	10	16	dep	treatment	1472:1480	arg1	response					1456:1463	response	1456:1463	response	1456:1463	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	7	17	theme	mouse	940:944	arg1	cells					965:969	cultured primary mouse aortic endothelial cells	923:969	cultured primary mouse aortic endothelial cells (MAECs)	923:977	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	7	17	theme	mouse	940:944	arg1	MAECs					972:976	MAECs	972:976	MAECs	972:976	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	3	18	theme	sialoglycan	307:317	arg1	ligands					319:325	sialoglycan ligands	307:325	sialoglycan ligands	307:325	When Siglec-E binds to sialoglycan ligands in its extracellular environment, it halts the immune cells' inflammatory responses.
31918287	13	19	theme	macrophages	1827:1837	arg1	co-incubation					1810:1822	co-incubation	1810:1822	co-incubation of macrophages with LPS-treated MAECs	1810:1860	Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.
31918287	9	20	theme	Siglec-E	1221:1228	arg1	ligands					1230:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	9	20	theme	Siglec-E	1221:1228	arg1	sialoglycoproteins					1251:1268	O-linked sialoglycoproteins	1242:1268	O-linked sialoglycoproteins with molecular weights of 70-300 kDa	1242:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	7	21	theme	cultured	923:930	arg1	cells					965:969	cultured primary mouse aortic endothelial cells	923:969	cultured primary mouse aortic endothelial cells (MAECs)	923:977	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	7	21	theme	cultured	923:930	arg1	MAECs					972:976	MAECs	972:976	MAECs	972:976	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	1	22	theme	human	130:134	arg1	Siglec-9					136:143	human Siglec-9	130:143	human Siglec-9	130:143	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	0	23	from	ligands	27:33	arg1	aorta					44:48	mouse aorta	38:48	mouse aorta	38:48	Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-κB pathway.
31918287	5	24	theme	glycoprotein	661:672	arg1	class					674:678	glycoprotein class	661:678	glycoprotein class	661:678	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	5	25	gly	glycoprotein	661:672	arg1	glycoprotein					661:672	glycoprotein class	661:678	glycoprotein class	661:678	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	3	26	theme	extracellular	334:346	arg1	environment					348:358	its extracellular environment	330:358	its extracellular environment	330:358	When Siglec-E binds to sialoglycan ligands in its extracellular environment, it halts the immune cells' inflammatory responses.
31918287	14	27	theme	Siglec-E	2059:2066	arg1	ligands					2068:2074	Siglec-E ligands	2059:2074	Siglec-E ligands	2059:2074	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	5	28	theme	mouse	703:707	arg1	aorta					709:713	mouse aorta	703:713	mouse aorta	703:713	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	10	29	theme	Siglec-E	1407:1414	arg1	ligands					1416:1422	Siglec-E ligands	1407:1422	Siglec-E ligands	1407:1422	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	9	30	theme	molecular	1275:1283	arg1	weights					1285:1291	molecular weights	1275:1291	molecular weights of 70-300 kDa	1275:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	5	31	dep	distribution	628:639	arg1	aorta					709:713	mouse aorta	703:713	mouse aorta	703:713	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	5	31	dep	distribution	628:639	arg1	The					624:626	The	624:626	The	624:626	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	13	32	with	co-incubation	1810:1822	arg1	MAECs					1856:1860	LPS-treated MAECs	1844:1860	LPS-treated MAECs	1844:1860	Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.
31918287	14	33	dep	inhibited	2151:2159	arg1	strategy					2224:2231	a therapeutic strategy	2210:2231	a therapeutic strategy to interfere with vascular inflammation	2210:2271	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	14	33	dep	inhibited	2151:2159	arg1	which					2197:2201	which	2197:2201	which	2197:2201	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	14	34	theme	therapeutic	2212:2222	arg1	strategy					2224:2231	a therapeutic strategy	2210:2231	a therapeutic strategy to interfere with vascular inflammation	2210:2271	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	14	34	theme	therapeutic	2212:2222	arg1	which					2197:2201	which	2197:2201	which	2197:2201	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	0	35	theme	Immunosuppressive	0:16	arg1	ligands					27:33	Immunosuppressive Siglec-E ligands	0:33	Immunosuppressive Siglec-E ligands on mouse aorta	0:48	Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-κB pathway.
31918287	4	36	theme	ligands	518:524	arg1	mechanisms					470:479	mechanisms	470:479	mechanisms of action	470:489	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	4	36	theme	ligands	518:524	arg1	expression					458:467	expression	458:467	expression	458:467	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	4	36	theme	ligands	518:524	arg1	regulation					495:504	regulation	495:504	regulation of Siglec-E ligands	495:524	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	6	37	theme	ligands	823:829	arg1	expression					800:809	the expression	796:809	the expression of Siglec-E ligands	796:829	In vivo, the expression of Siglec-E ligands was detected after LPS treatment, with or without NF-κB inhibitor administration.
31918287	4	38	theme	vascular	533:540	arg1	inflammation					542:553	vascular inflammation	533:553	vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta	533:613	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	11	39	theme	signaling	1614:1622	arg1	pathway					1624:1630	an NF-κB signaling pathway	1605:1630	an NF-κB signaling pathway	1605:1630	In MAECs, the expression of Siglec-E ligands was also increased by LPS via an NF-κB signaling pathway.
31918287	0	40	theme	mouse	38:42	arg1	aorta					44:48	mouse aorta	38:48	mouse aorta	38:48	Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-κB pathway.
31918287	12	41	theme	Siglec-E	1726:1733	arg1	ligands					1735:1741	Siglec-E ligands	1726:1741	Siglec-E ligands	1726:1741	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	3	42	theme	immune	374:379	arg1	responses					401:409	the immune cells' inflammatory responses	370:409	the immune cells' inflammatory responses	370:409	When Siglec-E binds to sialoglycan ligands in its extracellular environment, it halts the immune cells' inflammatory responses.
31918287	7	43	theme	NF-κB	1071:1075	arg1	inhibitors					1077:1086	NF-κB inhibitors	1071:1086	NF-κB inhibitors	1071:1086	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	5	44	from	METHODS	616:622	arg1	distribution					628:639	distribution	628:639	distribution	628:639	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	5	44	from	METHODS	616:622	arg1	size					652:655	molecular size	642:655	molecular size	642:655	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	5	44	from	METHODS	616:622	arg1	class					674:678	glycoprotein class	661:678	glycoprotein class	661:678	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	12	45	theme	multiple	1697:1704	arg1	carriers					1714:1721	multiple protein carriers	1697:1721	multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS	1697:1798	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	14	46	dep	inflammation	2134:2145	arg1	response					2101:2108	response	2101:2108	response	2101:2108	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	12	47	theme	carriers	1714:1721	arg1	carriers					1714:1721	multiple protein carriers	1697:1721	multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS	1697:1798	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	12	47	theme	carriers	1714:1721	arg1	one					1690:1692	one	1690:1692	one	1690:1692	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	2	48	located	found	234:238	arg2	Siglec-E					198:205	Siglec-E	198:205	Siglec-E	198:205	Both Siglec-E and Siglec-9 are primarily found on neutrophils, macrophages, and monocytes.
31918287	2	48	located	found	234:238	arg2	Siglec-9					211:218	Siglec-9	211:218	Siglec-9	211:218	Both Siglec-E and Siglec-9 are primarily found on neutrophils, macrophages, and monocytes.
31918287	2	48	located	found	234:238	arg1	macrophages					256:266	macrophages	256:266	macrophages	256:266	Both Siglec-E and Siglec-9 are primarily found on neutrophils, macrophages, and monocytes.
31918287	2	48	located	found	234:238	arg1	monocytes					273:281	monocytes	273:281	monocytes	273:281	Both Siglec-E and Siglec-9 are primarily found on neutrophils, macrophages, and monocytes.
31918287	2	48	located	found	234:238	arg1	neutrophils					243:253	neutrophils	243:253	neutrophils	243:253	Both Siglec-E and Siglec-9 are primarily found on neutrophils, macrophages, and monocytes.
31918287	10	49	theme	LPS	1468:1470	arg1	treatment					1472:1480	LPS treatment	1468:1480	LPS treatment	1468:1480	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	14	50	dep	CONCLUSIONS	2018:2028	arg1	demonstrated					2041:2052	demonstrated	2041:2052	demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation	2041:2271	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	7	51	from	changes	998:1004	arg1	expression					1009:1018	expression	1009:1018	expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors	1009:1086	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	14	52	theme	immune	2165:2170	arg1	response					2172:2179	the immune response	2161:2179	the immune response of macrophages	2161:2194	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	11	53	theme	Siglec-E	1558:1565	arg1	ligands					1567:1573	Siglec-E ligands	1558:1573	Siglec-E ligands	1558:1573	In MAECs, the expression of Siglec-E ligands was also increased by LPS via an NF-κB signaling pathway.
31918287	9	54	theme	in	1370:1371	arg1	MAECs					1364:1368	MAECs	1364:1368	MAECs in vitro	1364:1377	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	6	55	theme	LPS	850:852	arg1	treatment					854:862	LPS treatment	850:862	LPS treatment	850:862	In vivo, the expression of Siglec-E ligands was detected after LPS treatment, with or without NF-κB inhibitor administration.
31918287	4	56	theme	E.	566:567	arg1	LPS					595:597	LPS	595:597	LPS	595:597	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	4	56	theme	E.	566:567	arg1	lipopolysaccharides					574:592	E. coli lipopolysaccharides	566:592	E. coli lipopolysaccharides (LPS)	566:598	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	10	57	theme	NF-κB	1488:1492	arg1	pathway					1504:1510	NF-κB signaling pathway	1488:1510	NF-κB signaling pathway	1488:1510	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	7	58	theme	ligands	1032:1038	arg1	expression					1009:1018	expression	1009:1018	expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors	1009:1086	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	12	59	theme	brain	1654:1658	arg1	tumors-1					1660:1667	malignant brain tumors-1	1644:1667	malignant brain tumors-1	1644:1667	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	8	60	theme	increased	1162:1170	arg1	expression					1172:1181	increased expression	1162:1181	increased expression of Siglec-E ligands	1162:1201	MAECs induced by LPS were co-cultured with macrophages and the effect of increased expression of Siglec-E ligands analyzed.
31918287	13	61	theme	LPS-treated	1844:1854	arg1	MAECs					1856:1860	LPS-treated MAECs	1844:1860	LPS-treated MAECs	1844:1860	Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.
31918287	1	62	theme	immunosuppressive	152:168	arg1	receptor					183:190	an immunosuppressive cell surface receptor	149:190	an immunosuppressive cell surface receptor	149:190	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	1	62	theme	immunosuppressive	152:168	arg1	AIMS					93:96	AIMS Siglec-E	93:105	AIMS Siglec-E	93:105	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	14	63	theme	LPS-induced	2113:2123	arg1	inflammation					2134:2145	LPS-induced vascular inflammation	2113:2145	LPS-induced vascular inflammation	2113:2145	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	1	64	theme	surface	175:181	arg1	receptor					183:190	an immunosuppressive cell surface receptor	149:190	an immunosuppressive cell surface receptor	149:190	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	1	64	theme	surface	175:181	arg1	AIMS					93:96	AIMS Siglec-E	93:105	AIMS Siglec-E	93:105	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	8	65	theme	ligands	1195:1201	arg1	expression					1172:1181	increased expression	1162:1181	increased expression of Siglec-E ligands	1162:1201	MAECs induced by LPS were co-cultured with macrophages and the effect of increased expression of Siglec-E ligands analyzed.
31918287	5	66	theme	Siglec-E	683:690	arg1	ligands					692:698	Siglec-E ligands	683:698	Siglec-E ligands	683:698	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	5	67	theme	molecular	642:650	arg1	size					652:655	molecular size	642:655	molecular size	642:655	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	7	68	used	used	984:987	arg2	MAECs					972:976	MAECs	972:976	MAECs	972:976	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	7	68	used	used	984:987	arg2	cells					965:969	cultured primary mouse aortic endothelial cells	923:969	cultured primary mouse aortic endothelial cells (MAECs)	923:977	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	6	69	theme	NF-κB	881:885	arg1	administration					897:910	NF-κB inhibitor administration	881:910	NF-κB inhibitor administration	881:910	In vivo, the expression of Siglec-E ligands was detected after LPS treatment, with or without NF-κB inhibitor administration.
31918287	9	70	dep	in	1370:1371	arg1	vitro					1373:1377	vitro	1373:1377	vitro	1373:1377	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	1	71	theme	mouse	112:116	arg1	ortholog					118:125	the mouse ortholog	108:125	the mouse ortholog of human Siglec-9	108:143	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	1	71	theme	mouse	112:116	arg1	AIMS					93:96	AIMS Siglec-E	93:105	AIMS Siglec-E	93:105	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	9	72	with	sialoglycoproteins	1251:1268	arg1	weights					1285:1291	molecular weights	1275:1291	molecular weights of 70-300 kDa	1275:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	9	73	theme	RESULTS	1213:1219	arg1	ligands					1230:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	9	73	theme	RESULTS	1213:1219	arg1	sialoglycoproteins					1251:1268	O-linked sialoglycoproteins	1242:1268	O-linked sialoglycoproteins with molecular weights of 70-300 kDa	1242:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	7	74	theme	aortic	946:951	arg1	cells					965:969	cultured primary mouse aortic endothelial cells	923:969	cultured primary mouse aortic endothelial cells (MAECs)	923:977	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	7	74	theme	aortic	946:951	arg1	MAECs					972:976	MAECs	972:976	MAECs	972:976	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	9	75	gly	sialoglycoproteins	1251:1268	arg1	ligands					1230:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	9	75	gly	sialoglycoproteins	1251:1268	arg1	sialoglycoproteins					1251:1268	O-linked sialoglycoproteins	1242:1268	O-linked sialoglycoproteins with molecular weights of 70-300 kDa	1242:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	13	76	theme	Siglec-E	2000:2007	arg1	ligands					2009:2015	Siglec-E ligands	2000:2015	Siglec-E ligands	2000:2015	Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.
31918287	7	77	theme	primary	932:938	arg1	cells					965:969	cultured primary mouse aortic endothelial cells	923:969	cultured primary mouse aortic endothelial cells (MAECs)	923:977	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	7	77	theme	primary	932:938	arg1	MAECs					972:976	MAECs	972:976	MAECs	972:976	In vitro, cultured primary mouse aortic endothelial cells (MAECs) were used to study changes in expression of Siglec-E ligands induced by LPS with or without NF-κB inhibitors.
31918287	1	78	theme	Siglec-9	136:143	arg1	ortholog					118:125	the mouse ortholog	108:125	the mouse ortholog of human Siglec-9	108:143	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	1	78	theme	Siglec-9	136:143	arg1	AIMS					93:96	AIMS Siglec-E	93:105	AIMS Siglec-E	93:105	AIMS Siglec-E, the mouse ortholog of human Siglec-9, is an immunosuppressive cell surface receptor.
31918287	4	79	theme	action	484:489	arg1	mechanisms					470:479	mechanisms	470:479	mechanisms of action	470:489	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	4	79	theme	action	484:489	arg1	expression					458:467	expression	458:467	expression	458:467	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	4	79	theme	action	484:489	arg1	regulation					495:504	regulation	495:504	regulation of Siglec-E ligands	495:524	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	14	80	theme	vascular	2251:2258	arg1	inflammation					2260:2271	vascular inflammation	2251:2271	vascular inflammation	2251:2271	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	9	81	theme	O-linked	1242:1249	arg1	ligands					1230:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	9	81	theme	O-linked	1242:1249	arg1	sialoglycoproteins					1251:1268	O-linked sialoglycoproteins	1242:1268	O-linked sialoglycoproteins with molecular weights of 70-300 kDa	1242:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	5	82	theme	ligands	763:769	arg1	carrier					748:754	the protein carrier	736:754	the protein carrier of the ligands	736:769	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	9	83	theme	70-300 kDa	1296:1305	arg1	weights					1285:1291	molecular weights	1275:1291	molecular weights of 70-300 kDa	1275:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	9	84	link	O-linked	1242:1249	arg1	ligands					1230:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands	1213:1236	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	9	84	link	O-linked	1242:1249	arg1	sialoglycoproteins					1251:1268	O-linked sialoglycoproteins	1242:1268	O-linked sialoglycoproteins with molecular weights of 70-300 kDa	1242:1305	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	11	85	theme	NF-κB	1608:1612	arg1	pathway					1624:1630	an NF-κB signaling pathway	1605:1630	an NF-κB signaling pathway	1605:1630	In MAECs, the expression of Siglec-E ligands was also increased by LPS via an NF-κB signaling pathway.
31918287	5	86	theme	protein	740:746	arg1	carrier					748:754	the protein carrier	736:754	the protein carrier of the ligands	736:769	METHODS The distribution, molecular size and glycoprotein class of Siglec-E ligands on mouse aorta were determined, and the protein carrier of the ligands was identified.
31918287	6	87	theme	Siglec-E	814:821	arg1	ligands					823:829	Siglec-E ligands	814:829	Siglec-E ligands	814:829	In vivo, the expression of Siglec-E ligands was detected after LPS treatment, with or without NF-κB inhibitor administration.
31918287	3	88	theme	inflammatory	388:399	arg1	responses					401:409	the immune cells' inflammatory responses	370:409	the immune cells' inflammatory responses	370:409	When Siglec-E binds to sialoglycan ligands in its extracellular environment, it halts the immune cells' inflammatory responses.
31918287	10	89	theme	ligands	1416:1422	arg1	expression					1393:1402	the expression	1389:1402	the expression of Siglec-E ligands	1389:1422	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	12	90	theme	glycans	1748:1754	arg1	carriers					1714:1721	multiple protein carriers	1697:1721	multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS	1697:1798	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	13	91	theme	Siglec-E	1980:1987	arg1	binding					1989:1995	Siglec-E binding	1980:1995	Siglec-E binding to Siglec-E ligands	1980:2015	Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.
31918287	4	92	theme	Siglec-E	509:516	arg1	ligands					518:524	Siglec-E ligands	509:524	Siglec-E ligands	509:524	In the present study, we aimed to investigate expression, mechanisms of action and regulation of Siglec-E ligands during vascular inflammation induced by E. coli lipopolysaccharides (LPS) in mouse aorta.
31918287	9	93	theme	mouse	1338:1342	arg1	aorta					1344:1348	mouse aorta	1338:1348	mouse aorta	1338:1348	RESULTS Siglec-E ligands are O-linked sialoglycoproteins with molecular weights of 70-300 kDa and are distributed broadly on mouse aorta as well as on MAECs in vitro.
31918287	12	94	theme	ligands	1759:1765	arg1	ligands					1735:1741	Siglec-E ligands	1726:1741	Siglec-E ligands	1726:1741	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	12	94	theme	ligands	1759:1765	arg1	glycans					1748:1754	glycans	1748:1754	glycans of ligands involved in MAECs induced by LPS	1748:1798	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	12	95	theme	ligands	1735:1741	arg1	carriers					1714:1721	multiple protein carriers	1697:1721	multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS	1697:1798	Deleted in malignant brain tumors-1 was identified to be one of multiple protein carriers of Siglec-E ligands, and glycans of ligands involved in MAECs induced by LPS.
31918287	10	96	theme	mice	1441:1444	arg1	aortas					1446:1451	mice aortas	1441:1451	mice aortas	1441:1451	In vivo, the expression of Siglec-E ligands was increased in mice aortas in response to LPS treatment in an NF-κB signaling pathway dependent manner.
31918287	13	97	theme	macrophage	1905:1914	arg1	phagocytosis					1916:1927	macrophage phagocytosis	1905:1927	macrophage phagocytosis	1905:1927	Notably, co-incubation of macrophages with LPS-treated MAECs induced macrophage apoptosis and decreased macrophage phagocytosis, effects that were completely reversed by blocking Siglec-E binding to Siglec-E ligands.
31918287	14	98	theme	macrophages	2184:2194	arg1	response					2172:2179	the immune response	2161:2179	the immune response of macrophages	2161:2194	CONCLUSIONS These data demonstrated that Siglec-E ligands were highly expressed in response to LPS-induced vascular inflammation and inhibited the immune response of macrophages, which may be a therapeutic strategy to interfere with vascular inflammation.
31918287	11	99	theme	ligands	1567:1573	arg1	expression					1544:1553	the expression	1540:1553	the expression of Siglec-E ligands	1540:1573	In MAECs, the expression of Siglec-E ligands was also increased by LPS via an NF-κB signaling pathway.
31918287	0	100	theme	Siglec-E	18:25	arg1	ligands					27:33	Immunosuppressive Siglec-E ligands	0:33	Immunosuppressive Siglec-E ligands on mouse aorta	0:48	Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-κB pathway.
28409271	2	0	dep	Golgi	508:512	arg1	disorders					532:540	-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	520:990	oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	497:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	1	theme	Raf-1	1533:1537	arg1	proto-oncogene					1539:1552	Raf-1 proto-oncogene	1533:1552	Raf-1 proto-oncogene	1533:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	1	theme	Raf-1	1533:1537	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	2	theme	-congenital	520:530	arg1	disorders					532:540	-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	520:990	oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	497:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	3	theme	ECHS1	1869:1873	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	3	theme	ECHS1	1869:1873	arg1	deficiency					1876:1885	mitochondria (ECHS1) deficiency	1855:1885	mitochondria (ECHS1) deficiency	1855:1885	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	4	theme	B-Raf	1292:1296	arg1	GTPase					1277:1282	GTPase	1277:1282	GTPase (HRAS)	1277:1289	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	4	theme	B-Raf	1292:1296	arg1	proto-oncogene					1298:1311	B-Raf proto-oncogene	1292:1311	B-Raf proto-oncogene	1292:1311	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	5	theme	matrix	1904:1909	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	5	theme	matrix	1904:1909	arg1	enzyme					1911:1916	a mitochondrial matrix enzyme	1888:1916	a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1888:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	6	theme	reductase	724:732	arg1	deficiency					736:745	pyrroline-5-carboxylate reductase 1 deficiency	700:745	pyrroline-5-carboxylate reductase 1 deficiency	700:745	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	1	7	theme	several	232:238	arg1	errors					257:262	several different inborn errors	232:262	several different inborn errors of metabolism (IEM)	232:282	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	8	theme	tyrosine	1194:1201	arg1	RAF1					1580:1583	RAF1	1580:1583	RAF1	1580:1583	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	8	theme	tyrosine	1194:1201	arg1	kinase					1572:1577	[protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase	1185:1577	kinase	1572:1577	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	9	theme	kinase	1132:1137	arg1	defects					1139:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	10	theme	of	542:543	arg1	disorders					532:540	-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	520:990	oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	497:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	11	theme	ATPase	646:651	arg1	H+					653:654	ATPase H+	646:654	ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome	646:857	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	12	theme	SCYL1BP1	1080:1087	arg1	gene					1090:1093	GORAB or SCYL1BP1) gene	1071:1093	gene	1090:1093	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	13	theme	MAP	1127:1129	arg1	defects					1139:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	14	theme	pathway	1118:1124	arg1	defects					1139:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	15	theme	errors	1668:1673	arg1	list					1653:1656	the list	1649:1656	the list of inborn errors of metabolism associated with cutis laxa	1649:1714	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	16	theme	RIN2	893:896	arg1	mutations					899:907	Ras and Rab interactor 2 (RIN2) mutations	867:907	mutations	899:907	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	17	theme	subunit	672:678	arg1	gene					694:697	V0 subunit a2 (ATP6VOA2) gene	669:697	V0 subunit a2 (ATP6VOA2) gene	669:697	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	1	18	from	occurrence	218:227	arg1	errors					257:262	several different inborn errors	232:262	several different inborn errors of metabolism (IEM)	232:282	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	19	theme	Golgi	508:512	arg1	component					484:492	the component	480:492	the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	480:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	20	theme	glycosylation	611:623	arg1	disorder					583:590	combined disorder	574:590	combined disorder of N- and O-linked glycosylation	574:623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	1	21	theme	laxa	110:113	arg1	finding					93:99	Clinical finding	84:99	Clinical finding	84:99	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	22	dep	genes	1179:1183	arg1	RAF1					1580:1583	RAF1	1580:1583	RAF1	1580:1583	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	22	dep	genes	1179:1183	arg1	kinase					1572:1577	[protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase	1185:1577	kinase	1572:1577	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	23	theme	transaldolase	910:922	arg1	deficiency					924:933	transaldolase deficiency	910:933	transaldolase deficiency	910:933	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	24	theme	fatty	1981:1985	arg1	acids					1987:1991	fatty acids	1981:1991	fatty acids	1981:1991	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	25	theme	metabolism	1678:1687	arg1	errors					1668:1673	inborn errors	1661:1673	inborn errors of metabolism associated with cutis laxa	1661:1714	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	26	theme	exchange	1421:1428	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	26	theme	exchange	1421:1428	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	26	theme	exchange	1421:1428	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	26	theme	exchange	1421:1428	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	27	theme	repeat	1460:1465	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	27	theme	repeat	1460:1465	arg1	SHOC2					1485:1489	SHOC2	1485:1489	SHOC2	1485:1489	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	27	theme	repeat	1460:1465	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	28	theme	glycosylation	433:445	arg1	disorders					420:428	congenital disorders	409:428	alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia	389:1002	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	29	from	mutations	454:462	arg1	subunit					467:473	subunit 7	467:475	subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	467:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	30	theme	spiral	1971:1976	arg1	step					1944:1947	the second step	1933:1947	the second step of the beta-oxidation spiral of fatty acids	1933:1991	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	31	theme	GORAB	1071:1075	arg1	gene					1090:1093	GORAB or SCYL1BP1) gene	1071:1093	gene	1090:1093	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	1	32	theme	wrinkled	133:140	arg1	skin					174:177	wrinkled, redundant, sagging, nonelastic skin	133:177	wrinkled, redundant, sagging, nonelastic skin	133:177	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	33	theme	leucine	1447:1453	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	33	theme	leucine	1447:1453	arg1	SHOC2					1485:1489	SHOC2	1485:1489	SHOC2	1485:1489	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	33	theme	leucine	1447:1453	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	34	theme	due	626:628	arg1	complex					565:571	glycosylation (CDG) complex	545:571	glycosylation (CDG) complex	545:571	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	35	theme	RAB6-interacting	1053:1068	arg1	syndrome					326:333	Menkes syndrome	319:333	Menkes syndrome	319:333	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	0	36	theme	ECHS1	66:70	arg1	deficiency					72:81	ECHS1 deficiency	66:81	ECHS1 deficiency	66:81	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
28409271	2	37	theme	HRas	1256:1259	arg1	proto-oncogene					1261:1274	HRas proto-oncogene	1256:1274	HRas proto-oncogene	1256:1274	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	37	theme	HRas	1256:1259	arg1	PTPN11					1238:1243	PTPN11	1238:1243	PTPN11	1238:1243	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	38	from	mutations	1028:1036	arg1	golgin					1045:1050	the golgin	1041:1050	the golgin	1041:1050	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	39	dep	NRAS	1493:1496	arg1	proto-oncogene					1498:1511	proto-oncogene	1498:1511	proto-oncogene	1498:1511	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	39	dep	NRAS	1493:1496	arg1	proto-oncogene					1539:1552	Raf-1 proto-oncogene	1533:1552	Raf-1 proto-oncogene	1533:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	39	dep	NRAS	1493:1496	arg1	NRAS					1522:1525	NRAS	1522:1525	NRAS	1522:1525	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	39	dep	NRAS	1493:1496	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	39	dep	NRAS	1493:1496	arg1	GTPase					1514:1519	GTPase (NRAS)	1514:1526	GTPase (NRAS)	1514:1526	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	40	dep	gene	403:406	arg1	disorders					420:428	congenital disorders	409:428	alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia	389:1002	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	40	dep	gene	403:406	arg1	Gerodermia					993:1002	Gerodermia	993:1002	Gerodermia	993:1002	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	41	theme	Rab	875:877	arg1	mutations					899:907	Ras and Rab interactor 2 (RIN2) mutations	867:907	mutations	899:907	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	42	theme	CDG	560:562	arg1	complex					565:571	glycosylation (CDG) complex	545:571	glycosylation (CDG) complex	545:571	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	43	theme	clinical	1734:1741	arg1	presentation					1743:1754	the clinical presentation	1730:1754	the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1730:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	44	dep	copper	369:374	arg1	osteodysplastica					1004:1019	the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica	358:1019	the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin	358:1050	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	45	theme	Ras	867:869	arg1	mutations					899:907	Ras and Rab interactor 2 (RIN2) mutations	867:907	mutations	899:907	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	46	link	O-linked	602:609	arg1	glycosylation					611:623	O-linked glycosylation	602:623	O-linked glycosylation	602:623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	0	47	theme	Unique	0:5	arg1	presentation					7:18	Unique presentation	0:18	Unique presentation of cutis laxa with Leigh-like syndrome	0:57	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
28409271	1	48	theme	different	240:248	arg1	errors					257:262	several different inborn errors	232:262	several different inborn errors of metabolism (IEM)	232:282	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	1	49	theme	Clinical	84:91	arg1	finding					93:99	Clinical finding	84:99	Clinical finding	84:99	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	50	theme	guanine	1402:1408	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	50	theme	guanine	1402:1408	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	50	theme	guanine	1402:1408	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	50	theme	guanine	1402:1408	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	51	theme	coenzyme	1817:1824	arg1	enzyme					1911:1916	a mitochondrial matrix enzyme	1888:1916	a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1888:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	51	theme	coenzyme	1817:1824	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	51	theme	coenzyme	1817:1824	arg1	chain					1845:1849	short chain	1839:1849	short chain	1839:1849	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	51	theme	coenzyme	1817:1824	arg1	deficiency					1876:1885	mitochondria (ECHS1) deficiency	1855:1885	mitochondria (ECHS1) deficiency	1855:1885	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	52	theme	combined	574:581	arg1	disorder					583:590	combined disorder	574:590	combined disorder of N- and O-linked glycosylation	574:623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	53	theme	ATPase	362:367	arg1	copper					369:374	the ATPase copper	358:374	the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin	358:1050	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	54	theme	17-month-old	1761:1772	arg1	girl					1774:1777	a 17-month-old girl	1759:1777	a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1759:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	55	theme	SOS	1390:1392	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	55	theme	SOS	1390:1392	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	55	theme	SOS	1390:1392	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	55	theme	SOS	1390:1392	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	56	theme	cutis	817:821	arg1	laxa					823:826	cutis laxa	817:826	cutis laxa	817:826	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	57	from	mutations	1158:1166	arg1	genes					1179:1183	several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)	1171:1584	several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)	1171:1584	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	0	58	theme	laxa	29:32	arg1	presentation					7:18	Unique presentation	0:18	Unique presentation of cutis laxa with Leigh-like syndrome	0:57	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
28409271	1	59	theme	metabolism	267:276	arg1	errors					257:262	several different inborn errors	232:262	several different inborn errors of metabolism (IEM)	232:282	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	60	theme	non-receptor-type	1216:1232	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	60	theme	non-receptor-type	1216:1232	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	60	theme	non-receptor-type	1216:1232	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	60	theme	non-receptor-type	1216:1232	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	61	theme	short	1839:1843	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	61	theme	short	1839:1843	arg1	chain					1845:1849	short chain	1839:1849	short chain	1839:1849	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	62	theme	MACS	844:847	arg1	syndrome					850:857	scoliosis (MACS) syndrome	833:857	scoliosis (MACS) syndrome	833:857	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	63	theme	laxa	301:304	arg1	results					306:312	Metabolic cutis laxa results	285:312	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.	285:1623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	0	64	theme	Leigh-like	39:48	arg1	syndrome					50:57	Leigh-like syndrome	39:57	Leigh-like syndrome	39:57	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
28409271	2	65	theme	Ras-MAPK	1607:1614	arg1	cascade					1616:1622	the Ras-MAPK cascade	1603:1622	the Ras-MAPK cascade	1603:1622	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	66	theme	pyrroline-5-carboxylate	700:722	arg1	deficiency					736:745	pyrroline-5-carboxylate reductase 1 deficiency	700:745	pyrroline-5-carboxylate reductase 1 deficiency	700:745	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	67	theme	scoliosis	833:841	arg1	syndrome					850:857	scoliosis (MACS) syndrome	833:857	scoliosis (MACS) syndrome	833:857	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	68	theme	Metabolic	285:293	arg1	results					306:312	Metabolic cutis laxa results	285:312	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.	285:1623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	69	theme	transaldolase	962:974	arg1	gene					987:990	the transaldolase 1 (TALDO1) gene	958:990	the transaldolase 1 (TALDO1) gene	958:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	70	theme	several	1171:1177	arg1	genes					1179:1183	several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)	1171:1584	several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)	1171:1584	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	71	theme	KRAS	1354:1357	arg1	GTPase					1277:1282	GTPase	1277:1282	GTPase (HRAS)	1277:1289	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	71	theme	KRAS	1354:1357	arg1	proto-oncogene					1359:1372	KRAS proto-oncogene	1354:1372	KRAS proto-oncogene	1354:1372	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	72	theme	pyrroline-5-carboxylate	748:770	arg1	deficiency					781:790	pyrroline-5-carboxylate synthase deficiency	748:790	pyrroline-5-carboxylate synthase deficiency	748:790	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	73	dep	RAB6-interacting	1053:1068	arg1	caused					1148:1153	caused	1148:1153	caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)	1148:1584	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	74	theme	phosphatase	1203:1213	arg1	RAF1					1580:1583	RAF1	1580:1583	RAF1	1580:1583	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	74	theme	phosphatase	1203:1213	arg1	kinase					1572:1577	[protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase	1185:1577	kinase	1572:1577	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	75	dep	caused	1148:1153	arg1	gene					1090:1093	GORAB or SCYL1BP1) gene	1071:1093	gene	1090:1093	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	76	theme	V0	669:670	arg1	gene					694:697	V0 subunit a2 (ATP6VOA2) gene	669:697	V0 subunit a2 (ATP6VOA2) gene	669:697	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	77	from	mutations	945:953	arg1	gene					987:990	the transaldolase 1 (TALDO1) gene	958:990	the transaldolase 1 (TALDO1) gene	958:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	78	theme	[protein	1185:1192	arg1	RAF1					1580:1583	RAF1	1580:1583	RAF1	1580:1583	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	78	theme	[protein	1185:1192	arg1	kinase					1572:1577	[protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase	1185:1577	kinase	1572:1577	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	79	theme	serine/threonine	1555:1570	arg1	RAF1					1580:1583	RAF1	1580:1583	RAF1	1580:1583	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	79	theme	serine/threonine	1555:1570	arg1	kinase					1572:1577	[protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase	1185:1577	kinase	1572:1577	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	80	theme	glycosylation	545:557	arg1	complex					565:571	glycosylation (CDG) complex	545:571	glycosylation (CDG) complex	545:571	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	81	theme	mitochondrial	1890:1902	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	81	theme	mitochondrial	1890:1902	arg1	enzyme					1911:1916	a mitochondrial matrix enzyme	1888:1916	a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1888:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	82	dep	disorders	532:540	arg1	complex					565:571	glycosylation (CDG) complex	545:571	glycosylation (CDG) complex	545:571	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	83	theme	serine/threonine	1314:1329	arg1	GTPase					1277:1282	GTPase	1277:1282	GTPase (HRAS)	1277:1289	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	83	theme	serine/threonine	1314:1329	arg1	BRAF					1339:1342	BRAF	1339:1342	BRAF	1339:1342	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	83	theme	serine/threonine	1314:1329	arg1	kinase					1331:1336	serine/threonine kinase	1314:1336	serine/threonine kinase (BRAF)	1314:1343	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	84	theme	amino	2024:2028	arg1	catabolism					2035:2044	amino acid catabolism	2024:2044	amino acid catabolism	2024:2044	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	84	theme	amino	2024:2028	arg1	valine					2060:2065	valine	2060:2065	valine	2060:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	85	theme	ATP6VOA2	684:691	arg1	gene					694:697	V0 subunit a2 (ATP6VOA2) gene	669:697	V0 subunit a2 (ATP6VOA2) gene	669:697	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	86	from	syndrome	326:333	arg1	results					306:312	Metabolic cutis laxa results	285:312	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.	285:1623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	87	theme	inborn	1661:1666	arg1	errors					1668:1673	inborn errors	1661:1673	inborn errors of metabolism associated with cutis laxa	1661:1714	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	88	with	girl	1774:1777	arg1	syndrome					1795:1802	Leigh-like syndrome	1784:1802	Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1784:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	89	theme	second	1937:1942	arg1	step					1944:1947	the second step	1933:1947	the second step of the beta-oxidation spiral of fatty acids	1933:1991	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	90	theme	a2	680:681	arg1	gene					694:697	V0 subunit a2 (ATP6VOA2) gene	669:697	V0 subunit a2 (ATP6VOA2) gene	669:697	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	91	theme	mitogen-activated	1100:1116	arg1	defects					1139:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	mitogen-activated pathway (MAP) kinase defects	1100:1145	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	92	theme	beta-oxidation	1956:1969	arg1	spiral					1971:1976	the beta-oxidation spiral	1952:1976	the beta-oxidation spiral of fatty acids	1952:1991	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	93	from	mutations	633:641	arg1	H+					653:654	ATPase H+	646:654	ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome	646:857	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	1	94	theme	cutis	104:108	arg1	laxa					110:113	cutis laxa	104:113	cutis laxa	104:113	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	95	theme	oligomeric	497:506	arg1	COG7					515:518	COG7	515:518	COG7	515:518	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	95	theme	oligomeric	497:506	arg1	Golgi					508:512	oligomeric Golgi	497:512	oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	497:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	96	theme	O-linked	602:609	arg1	glycosylation					611:623	O-linked glycosylation	602:623	O-linked glycosylation	602:623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	97	theme	scaffold	1467:1474	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	97	theme	scaffold	1467:1474	arg1	SHOC2					1485:1489	SHOC2	1485:1489	SHOC2	1485:1489	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	97	theme	scaffold	1467:1474	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	98	theme	component	484:492	arg1	subunit					467:473	subunit 7	467:475	subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	467:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	99	theme	acids	1987:1991	arg1	spiral					1971:1976	the beta-oxidation spiral	1952:1976	the beta-oxidation spiral of fatty acids	1952:1991	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	100	dep	mutations	899:907	arg1	caused					935:940	caused	935:940	caused by mutations in the transaldolase 1 (TALDO1) gene	935:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	101	theme	nucleotide	1410:1419	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	101	theme	nucleotide	1410:1419	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	101	theme	nucleotide	1410:1419	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	101	theme	nucleotide	1410:1419	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	102	theme	rich	1455:1458	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	102	theme	rich	1455:1458	arg1	SHOC2					1485:1489	SHOC2	1485:1489	SHOC2	1485:1489	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	102	theme	rich	1455:1458	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	103	theme	cutis	1705:1709	arg1	laxa					1711:1714	cutis laxa	1705:1714	cutis laxa	1705:1714	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	104	theme	congenital	409:418	arg1	disorders					420:428	congenital disorders	409:428	alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia	389:1002	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	105	dep	complex	565:571	arg1	disorder					583:590	combined disorder	574:590	combined disorder of N- and O-linked glycosylation	574:623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	106	theme	interactor	879:888	arg1	mutations					899:907	Ras and Rab interactor 2 (RIN2) mutations	867:907	mutations	899:907	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	107	dep	due	626:628	arg1	due					860:862	due	860:862	due	860:862	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	108	theme	A	1826:1826	arg1	enzyme					1911:1916	a mitochondrial matrix enzyme	1888:1916	a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1888:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	108	theme	A	1826:1826	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	108	theme	A	1826:1826	arg1	chain					1845:1849	short chain	1839:1849	short chain	1839:1849	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	108	theme	A	1826:1826	arg1	deficiency					1876:1885	mitochondria (ECHS1) deficiency	1855:1885	mitochondria (ECHS1) deficiency	1855:1885	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	109	theme	due	447:449	arg1	glycosylation					433:445	glycosylation	433:445	glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene	433:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	110	theme	N-	595:596	arg1	disorder					583:590	combined disorder	574:590	combined disorder of N- and O-linked glycosylation	574:623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	111	theme	TALDO1	979:984	arg1	gene					987:990	the transaldolase 1 (TALDO1) gene	958:990	the transaldolase 1 (TALDO1) gene	958:990	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	112	theme	girl	1774:1777	arg1	presentation					1743:1754	the clinical presentation	1730:1754	the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1730:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	113	theme	enoyl	1811:1815	arg1	enzyme					1911:1916	a mitochondrial matrix enzyme	1888:1916	a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1888:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	113	theme	enoyl	1811:1815	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	113	theme	enoyl	1811:1815	arg1	chain					1845:1849	short chain	1839:1849	short chain	1839:1849	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	113	theme	enoyl	1811:1815	arg1	deficiency					1876:1885	mitochondria (ECHS1) deficiency	1855:1885	mitochondria (ECHS1) deficiency	1855:1885	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	114	theme	alpha	389:393	arg1	gene					403:406	alpha (ATP7A) gene	389:406	alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia	389:1002	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	115	theme	due	1021:1023	arg1	copper					369:374	the ATPase copper	358:374	the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin	358:1050	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	0	116	theme	cutis	23:27	arg1	laxa					29:32	cutis laxa	23:32	cutis laxa	23:32	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
28409271	1	117	theme	inborn	250:255	arg1	errors					257:262	several different inborn errors	232:262	several different inborn errors of metabolism (IEM)	232:282	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	2	118	theme	PTPN11	1238:1243	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	118	theme	PTPN11	1238:1243	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	118	theme	PTPN11	1238:1243	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	118	theme	PTPN11	1238:1243	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	119	theme	Ras/Rho	1394:1400	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	119	theme	Ras/Rho	1394:1400	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	119	theme	Ras/Rho	1394:1400	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	119	theme	Ras/Rho	1394:1400	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	1	120	dep	wrinkled	133:140	arg1	nonelastic					163:172	nonelastic	163:172	nonelastic	163:172	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	1	120	dep	wrinkled	133:140	arg1	sagging					154:160	sagging	154:160	sagging	154:160	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	1	120	dep	wrinkled	133:140	arg1	redundant					143:151	redundant	143:151	redundant	143:151	Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM).
28409271	3	121	theme	due	1804:1806	arg1	syndrome					1795:1802	Leigh-like syndrome	1784:1802	Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1784:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	122	dep	kinase	1572:1577	arg1	factor					1430:1435	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2	1216:1437	non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2)	1216:1444	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	122	dep	kinase	1572:1577	arg1	SOS2					1440:1443	SOS2	1440:1443	SOS2	1440:1443	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	122	dep	kinase	1572:1577	arg1	NRAS					1493:1496	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene	1493:1552	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	122	dep	kinase	1572:1577	arg1	protein					1476:1482	leucine rich repeat scaffold protein	1447:1482	leucine rich repeat scaffold protein (SHOC2)	1447:1490	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	123	theme	important	2006:2014	arg1	role					2016:2019	an important role	2003:2019	an important role	2003:2019	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	124	theme	Leigh-like	1784:1793	arg1	syndrome					1795:1802	Leigh-like syndrome	1784:1802	Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1784:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	125	theme	mitochondria	1855:1866	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	125	theme	mitochondria	1855:1866	arg1	deficiency					1876:1885	mitochondria (ECHS1) deficiency	1855:1885	mitochondria (ECHS1) deficiency	1855:1885	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	2	126	theme	ATP7A	396:400	arg1	gene					403:406	alpha (ATP7A) gene	389:406	alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia	389:1002	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	0	127	with	presentation	7:18	arg1	syndrome					50:57	Leigh-like syndrome	39:57	Leigh-like syndrome	39:57	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
28409271	2	128	theme	cutis	295:299	arg1	results					306:312	Metabolic cutis laxa results	285:312	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.	285:1623	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	3	129	theme	acid	2030:2033	arg1	catabolism					2035:2044	amino acid catabolism	2024:2044	amino acid catabolism	2024:2044	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	129	theme	acid	2030:2033	arg1	valine					2060:2065	valine	2060:2065	valine	2060:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	130	theme	1	1852:1852	arg1	enzyme					1911:1916	a mitochondrial matrix enzyme	1888:1916	a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine	1888:2065	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	130	theme	1	1852:1852	arg1	hydratase					1828:1836	enoyl coenzyme A hydratase	1811:1836	enoyl coenzyme A hydratase	1811:1836	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	130	theme	1	1852:1852	arg1	chain					1845:1849	short chain	1839:1849	short chain	1839:1849	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	3	130	theme	1	1852:1852	arg1	deficiency					1876:1885	mitochondria (ECHS1) deficiency	1855:1885	mitochondria (ECHS1) deficiency	1855:1885	Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
28409271	0	131	dep	presentation	7:18	arg1	deficiency					72:81	ECHS1 deficiency	66:81	ECHS1 deficiency	66:81	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency.
28409271	2	132	from	defect	348:353	arg1	copper					369:374	the ATPase copper	358:374	the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin	358:1050	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	133	theme	synthase	772:779	arg1	deficiency					781:790	pyrroline-5-carboxylate synthase deficiency	748:790	pyrroline-5-carboxylate synthase deficiency	748:790	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28409271	2	134	theme	Menkes	319:324	arg1	syndrome					326:333	Menkes syndrome	319:333	Menkes syndrome	319:333	Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade.
28017896	6	0	theme	augmented	973:981	arg1	signaling					992:1000	augmented O-GlcNAc signaling	973:1000	augmented O-GlcNAc signaling via glucosamine	973:1016	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	10	1	theme	Bcl-2	1828:1832	arg1	levels					1743:1748	the protein expression levels	1720:1748	the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2	1720:1832	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	7	2	theme	CI-AKI	1175:1180	arg1	model					1182:1186	a novel and reliable CI-AKI model	1154:1186	a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h	1154:1342	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	2	3	theme	extensive	311:319	arg1	study					321:325	extensive study	311:325	extensive study of a variety of agents for renal protection	311:369	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	2	4	theme	variety	332:338	arg1	study					321:325	extensive study	311:325	extensive study of a variety of agents for renal protection	311:369	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	1	5	theme	iatrogenic	195:204	arg1	injury					212:217	an iatrogenic renal injury	192:217	an iatrogenic renal injury	192:217	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	5	theme	iatrogenic	195:204	arg1	injury					173:178	Contrast-induced acute kidney injury	143:178	Contrast-induced acute kidney injury (CI-AKI)	143:187	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	4	6	theme	O-GlcNAc	676:683	arg1	levels					685:690	O-GlcNAc levels	676:690	O-GlcNAc levels	676:690	Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective.
28017896	10	7	theme	Nrf2	1818:1821	arg1	levels					1743:1748	the protein expression levels	1720:1748	the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2	1720:1832	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	5	8	theme	media	905:909	arg1	insults					911:917	contrast media insults	896:917	contrast media insults	896:917	However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown.
28017896	10	9	theme	O-GlcNAc	1686:1693	arg1	signaling					1695:1703	Augmented O-GlcNAc signaling	1676:1703	Augmented O-GlcNAc signaling	1676:1703	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	3	10	theme	nuclear	633:639	arg1	proteins					604:611	numerous proteins	595:611	numerous proteins	595:611	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	8	11	theme	renal	1502:1506	arg1	dysfunction					1508:1518	renal dysfunction	1502:1518	renal dysfunction	1502:1518	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	3	12	theme	cytosolic	619:627	arg1	proteins					604:611	numerous proteins	595:611	numerous proteins	595:611	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	6	13	theme	signaling	992:1000	arg1	effect					963:968	the effect	959:968	the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI	959:1026	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	0	14	from	injury	127:132	arg1	rats					137:140	rats	137:140	rats	137:140	Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.
28017896	7	15	theme	5/6	1202:1204	arg1	rats					1226:1229	5/6 nephrectomized (NE) rats	1202:1229	5/6 nephrectomized (NE) rats	1202:1229	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	4	16	theme	reaction	764:771	arg1	augmentation					743:754	acute augmentation	737:754	acute augmentation of this reaction	737:771	Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective.
28017896	14	17	theme	promising	2416:2424	arg1	strategy					2426:2433	a promising strategy	2414:2433	a promising strategy for preventing CI-AKI	2414:2455	Collectively, the results demonstrate that glucosamine induces renoprotection against CI-AKI through augmented O-GlcNAc and activation of PI3K/Akt signaling, making it a promising strategy for preventing CI-AKI.
28017896	10	18	theme	Bax	1863:1865	arg1	levels					1853:1858	the levels	1849:1858	the levels of Bax and cleaved caspase-3	1849:1887	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	1	19	theme	acute	160:164	arg1	injury					212:217	an iatrogenic renal injury	192:217	an iatrogenic renal injury	192:217	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	19	theme	acute	160:164	arg1	injury					173:178	Contrast-induced acute kidney injury	143:178	Contrast-induced acute kidney injury (CI-AKI)	143:187	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	19	theme	acute	160:164	arg1	CI-AKI					181:186	CI-AKI	181:186	CI-AKI	181:186	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	8	20	theme	damage	1529:1534	arg1	attenuation					1487:1497	the attenuation	1483:1497	the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress	1483:1566	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	8	21	theme	apoptosis	1537:1545	arg1	attenuation					1487:1497	the attenuation	1483:1497	the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress	1483:1566	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	4	22	theme	acute	737:741	arg1	augmentation					743:754	acute augmentation	737:754	acute augmentation of this reaction	737:771	Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective.
28017896	8	23	theme	oxidative	1551:1559	arg1	stress					1561:1566	oxidative stress	1551:1566	oxidative stress	1551:1566	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	14	24	theme	PI3K/Akt	2384:2391	arg1	signaling					2393:2401	PI3K/Akt signaling	2384:2401	PI3K/Akt signaling	2384:2401	Collectively, the results demonstrate that glucosamine induces renoprotection against CI-AKI through augmented O-GlcNAc and activation of PI3K/Akt signaling, making it a promising strategy for preventing CI-AKI.
28017896	0	25	theme	acute	114:118	arg1	injury					127:132	contrast-induced acute kidney injury	97:132	contrast-induced acute kidney injury in rats	97:140	Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.
28017896	10	26	theme	phospho-GSK-3β	1802:1815	arg1	levels					1743:1748	the protein expression levels	1720:1748	the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2	1720:1832	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	6	27	theme	underlying	1045:1054	arg1	mechanisms					1066:1075	the underlying molecular mechanisms	1041:1075	the underlying molecular mechanisms	1041:1075	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	6	27	theme	underlying	1045:1054	arg1	relationship					1095:1106	its relationship	1091:1106	its relationship with PI3-kinase (PI3K)/Akt signaling	1091:1143	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	8	28	theme	O-GlcNAc	1379:1386	arg1	signaling					1388:1396	augmented O-GlcNAc signaling	1369:1396	augmented O-GlcNAc signaling by glucosamine	1369:1411	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	10	29	theme	protein	1724:1730	arg1	levels					1743:1748	the protein expression levels	1720:1748	the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2	1720:1832	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	4	30	dep	stress	721:726	arg1	response					709:716	response	709:716	response	709:716	Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective.
28017896	0	31	theme	Augmented	0:8	arg1	signaling					19:27	Augmented O-GlcNAc signaling	0:27	Augmented O-GlcNAc signaling via glucosamine	0:43	Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.
28017896	13	32	mod	modified	2150:2157	arg1	Akt					2142:2144	Akt	2142:2144	Akt	2142:2144	We confirmed that Akt was modified by O-GlcNAcylation, and glucosamine pretreatment increased the O-GlcNAcylation of Akt.
28017896	13	32	mod	modified	2150:2157	arg3	O-GlcNAcylation					2162:2176	O-GlcNAcylation	2162:2176	O-GlcNAcylation	2162:2176	We confirmed that Akt was modified by O-GlcNAcylation, and glucosamine pretreatment increased the O-GlcNAcylation of Akt.
28017896	6	33	theme	/Akt	1130:1133	arg1	signaling					1135:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	2	34	theme	CI-AKI	443:448	arg1	reduction					430:438	the reduction	426:438	the reduction of CI-AKI	426:448	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	7	35	dep	media	1259:1263	arg1	3.5gI					1284:1288	3.5gI	1284:1288	3.5gI	1284:1288	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	7	35	dep	media	1259:1263	arg1	10mL/kg					1275:1281	10mL/kg	1275:1281	10mL/kg	1275:1281	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	7	35	dep	media	1259:1263	arg1	iohexol					1266:1272	iohexol	1266:1272	iohexol	1266:1272	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	10	36	theme	phospho-Akt	1753:1763	arg1	levels					1743:1748	the protein expression levels	1720:1748	the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2	1720:1832	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	11	37	dep	inhibitors	1916:1925	arg1	LY294002					1951:1958	LY294002	1951:1958	LY294002	1951:1958	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	11	37	dep	inhibitors	1916:1925	arg1	Wortmannin					1936:1945	Wortmannin	1936:1945	Wortmannin	1936:1945	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	11	37	dep	inhibitors	1916:1925	arg1	inhibitors					1916:1925	specific inhibitors	1907:1925	specific inhibitors of PI3K (Wortmannin and LY294002)	1907:1959	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	6	38	theme	PI3K	1125:1128	arg1	signaling					1135:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	9	39	theme	O-GlcNAc	1644:1651	arg1	inhibitor					1665:1673	an O-GlcNAc transferase inhibitor	1641:1673	an O-GlcNAc transferase inhibitor	1641:1673	Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor.
28017896	9	39	theme	O-GlcNAc	1644:1651	arg1	alloxan					1632:1638	alloxan	1632:1638	alloxan	1632:1638	Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor.
28017896	6	40	theme	PI3-kinase	1113:1122	arg1	signaling					1135:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	10	41	theme	cleaved	1871:1877	arg1	caspase-3					1879:1887	cleaved caspase-3	1871:1887	cleaved caspase-3	1871:1887	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	8	42	theme	iohexol-induced	1443:1457	arg1	injury					1459:1464	iohexol-induced injury	1443:1464	iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress	1443:1566	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	3	43	theme	post-translational	498:515	arg1	β-N-acetylglucosamine					460:480	O-linked β-N-acetylglucosamine	451:480	O-linked β-N-acetylglucosamine (O-GlcNAc)	451:491	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	43	theme	post-translational	498:515	arg1	modification					528:539	a post-translational regulatory modification	496:539	a post-translational regulatory modification of intracellular proteins	496:565	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	5	44	theme	OGlcNAc	846:852	arg1	signaling					854:862	augmented OGlcNAc signaling	836:862	augmented OGlcNAc signaling	836:862	However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown.
28017896	7	45	theme	tail	1308:1311	arg1	vein					1313:1316	the tail vein	1304:1316	the tail vein after dehydration for 48h	1304:1342	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	13	46	theme	Akt	2241:2243	arg1	O-GlcNAcylation					2222:2236	the O-GlcNAcylation	2218:2236	the O-GlcNAcylation of Akt	2218:2243	We confirmed that Akt was modified by O-GlcNAcylation, and glucosamine pretreatment increased the O-GlcNAcylation of Akt.
28017896	3	47	theme	intracellular	544:556	arg1	proteins					558:565	intracellular proteins	544:565	intracellular proteins	544:565	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	6	48	theme	O-GlcNAc	983:990	arg1	signaling					992:1000	augmented O-GlcNAc signaling	973:1000	augmented O-GlcNAc signaling via glucosamine	973:1016	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	2	49	from	reduction	430:438	arg1	effective					413:421	effective	413:421	effective	413:421	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	5	50	theme	underlying	805:814	arg1	unknown					928:934	unknown	928:934	unknown	928:934	However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown.
28017896	5	50	theme	underlying	805:814	arg1	mechanisms					816:825	the underlying mechanisms	801:825	the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults	801:917	However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown.
28017896	2	51	theme	limited	372:378	arg1	strategies					380:389	limited strategies	372:389	limited strategies	372:389	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	7	52	theme	reliable	1166:1173	arg1	model					1182:1186	a novel and reliable CI-AKI model	1154:1186	a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h	1154:1342	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	10	53	dep	phospho-Akt	1753:1763	arg1	Thr308					1782:1787	Thr308	1782:1787	Thr308	1782:1787	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	10	53	dep	phospho-Akt	1753:1763	arg1	Ser473					1766:1771	Ser473	1766:1771	Ser473	1766:1771	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	1	54	theme	susceptible	278:288	arg1	individuals					290:300	susceptible individuals	278:300	susceptible individuals	278:300	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	7	55	used	used	1149:1152	arg2	We					1146:1147	We	1146:1147	We	1146:1147	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	7	56	theme	novel	1156:1160	arg1	model					1182:1186	a novel and reliable CI-AKI model	1154:1186	a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h	1154:1342	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	0	57	theme	oxidative	56:64	arg1	stress					66:71	oxidative stress	56:71	oxidative stress	56:71	Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.
28017896	3	58	theme	proteins	604:611	arg1	function					583:590	the function	579:590	the function of numerous proteins, both cytosolic and nuclear	579:639	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	59	link	O-linked	451:458	arg1	O-GlcNAc					483:490	O-GlcNAc	483:490	O-GlcNAc	483:490	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	59	link	O-linked	451:458	arg1	modification					528:539	a post-translational regulatory modification	496:539	a post-translational regulatory modification of intracellular proteins	496:565	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	59	link	O-linked	451:458	arg1	β-N-acetylglucosamine					460:480	O-linked β-N-acetylglucosamine	451:480	O-linked β-N-acetylglucosamine (O-GlcNAc)	451:491	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	9	60	with	treatment	1617:1625	arg1	inhibitor					1665:1673	an O-GlcNAc transferase inhibitor	1641:1673	an O-GlcNAc transferase inhibitor	1641:1673	Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor.
28017896	9	60	with	treatment	1617:1625	arg1	alloxan					1632:1638	alloxan	1632:1638	alloxan	1632:1638	Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor.
28017896	5	61	theme	contrast	896:903	arg1	insults					911:917	contrast media insults	896:917	contrast media insults	896:917	However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown.
28017896	2	62	theme	renal	354:358	arg1	protection					360:369	renal protection	354:369	renal protection	354:369	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	1	63	from	mortality	265:273	arg1	individuals					290:300	susceptible individuals	278:300	susceptible individuals	278:300	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	8	64	theme	dysfunction	1508:1518	arg1	attenuation					1487:1497	the attenuation	1483:1497	the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress	1483:1566	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	10	65	theme	Augmented	1676:1684	arg1	signaling					1695:1703	Augmented O-GlcNAc signaling	1676:1703	Augmented O-GlcNAc signaling	1676:1703	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	7	66	theme	low-osmolar	1238:1248	arg1	media					1259:1263	a low-osmolar contrast media	1236:1263	a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI)	1236:1289	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	1	67	from	morbidity	251:259	arg1	individuals					290:300	susceptible individuals	278:300	susceptible individuals	278:300	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	13	68	theme	glucosamine	2183:2193	arg1	pretreatment					2195:2206	glucosamine pretreatment	2183:2206	glucosamine pretreatment	2183:2206	We confirmed that Akt was modified by O-GlcNAcylation, and glucosamine pretreatment increased the O-GlcNAcylation of Akt.
28017896	8	69	theme	tubular	1521:1527	arg1	damage					1529:1534	tubular damage	1521:1534	tubular damage	1521:1534	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	6	70	with	relationship	1095:1106	arg1	signaling					1135:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	PI3-kinase (PI3K)/Akt signaling	1113:1143	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	11	71	theme	Akt	2014:2016	arg1	pathway					2028:2034	Akt signaling pathway	2014:2034	Akt signaling pathway	2014:2034	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	1	72	theme	Contrast-induced	143:158	arg1	injury					212:217	an iatrogenic renal injury	192:217	an iatrogenic renal injury	192:217	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	72	theme	Contrast-induced	143:158	arg1	injury					173:178	Contrast-induced acute kidney injury	143:178	Contrast-induced acute kidney injury (CI-AKI)	143:187	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	72	theme	Contrast-induced	143:158	arg1	CI-AKI					181:186	CI-AKI	181:186	CI-AKI	181:186	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	73	theme	renal	206:210	arg1	injury					212:217	an iatrogenic renal injury	192:217	an iatrogenic renal injury	192:217	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	73	theme	renal	206:210	arg1	injury					173:178	Contrast-induced acute kidney injury	143:178	Contrast-induced acute kidney injury (CI-AKI)	143:187	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	74	theme	kidney	166:171	arg1	injury					212:217	an iatrogenic renal injury	192:217	an iatrogenic renal injury	192:217	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	74	theme	kidney	166:171	arg1	injury					173:178	Contrast-induced acute kidney injury	143:178	Contrast-induced acute kidney injury (CI-AKI)	143:187	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	1	74	theme	kidney	166:171	arg1	CI-AKI					181:186	CI-AKI	181:186	CI-AKI	181:186	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	7	75	theme	contrast	1250:1257	arg1	media					1259:1263	a low-osmolar contrast media	1236:1263	a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI)	1236:1289	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	0	76	theme	contrast-induced	97:112	arg1	injury					127:132	contrast-induced acute kidney injury	97:132	contrast-induced acute kidney injury in rats	97:140	Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.
28017896	8	77	theme	stress	1561:1566	arg1	attenuation					1487:1497	the attenuation	1483:1497	the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress	1483:1566	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	12	78	theme	western	2110:2116	arg1	blot					2118:2121	western blot	2110:2121	western blot	2110:2121	We further identified O-GlcNAcylated Akt through immunoprecipitation and western blot.
28017896	14	79	theme	signaling	2393:2401	arg1	activation					2370:2379	activation	2370:2379	activation	2370:2379	Collectively, the results demonstrate that glucosamine induces renoprotection against CI-AKI through augmented O-GlcNAc and activation of PI3K/Akt signaling, making it a promising strategy for preventing CI-AKI.
28017896	14	79	theme	signaling	2393:2401	arg1	O-GlcNAc					2357:2364	O-GlcNAc	2357:2364	O-GlcNAc	2357:2364	Collectively, the results demonstrate that glucosamine induces renoprotection against CI-AKI through augmented O-GlcNAc and activation of PI3K/Akt signaling, making it a promising strategy for preventing CI-AKI.
28017896	0	80	theme	kidney	120:125	arg1	injury					127:132	contrast-induced acute kidney injury	97:132	contrast-induced acute kidney injury in rats	97:140	Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.
28017896	3	81	theme	numerous	595:602	arg1	proteins					604:611	numerous proteins	595:611	numerous proteins	595:611	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	6	82	theme	molecular	1056:1064	arg1	mechanisms					1066:1075	the underlying molecular mechanisms	1041:1075	the underlying molecular mechanisms	1041:1075	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	6	82	theme	molecular	1056:1064	arg1	relationship					1095:1106	its relationship	1091:1106	its relationship with PI3-kinase (PI3K)/Akt signaling	1091:1143	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	8	83	theme	augmented	1369:1377	arg1	signaling					1388:1396	augmented O-GlcNAc signaling	1369:1396	augmented O-GlcNAc signaling by glucosamine	1369:1411	The results showed that augmented O-GlcNAc signaling by glucosamine prevented the kidneys against iohexol-induced injury characterized by the attenuation of renal dysfunction, tubular damage, apoptosis and oxidative stress.
28017896	3	84	theme	O-linked	451:458	arg1	O-GlcNAc					483:490	O-GlcNAc	483:490	O-GlcNAc	483:490	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	84	theme	O-linked	451:458	arg1	modification					528:539	a post-translational regulatory modification	496:539	a post-translational regulatory modification of intracellular proteins	496:565	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	84	theme	O-linked	451:458	arg1	β-N-acetylglucosamine					460:480	O-linked β-N-acetylglucosamine	451:480	O-linked β-N-acetylglucosamine (O-GlcNAc)	451:491	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	0	85	theme	O-GlcNAc	10:17	arg1	signaling					19:27	Augmented O-GlcNAc signaling	0:27	Augmented O-GlcNAc signaling via glucosamine	0:43	Augmented O-GlcNAc signaling via glucosamine attenuates oxidative stress and apoptosis following contrast-induced acute kidney injury in rats.
28017896	14	86	theme	augmented	2347:2355	arg1	O-GlcNAc					2357:2364	O-GlcNAc	2357:2364	O-GlcNAc	2357:2364	Collectively, the results demonstrate that glucosamine induces renoprotection against CI-AKI through augmented O-GlcNAc and activation of PI3K/Akt signaling, making it a promising strategy for preventing CI-AKI.
28017896	11	87	theme	PI3K	1930:1933	arg1	LY294002					1951:1958	LY294002	1951:1958	LY294002	1951:1958	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	11	87	theme	PI3K	1930:1933	arg1	Wortmannin					1936:1945	Wortmannin	1936:1945	Wortmannin	1936:1945	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	11	87	theme	PI3K	1930:1933	arg1	alloxan					1895:1901	alloxan	1895:1901	alloxan	1895:1901	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	11	87	theme	PI3K	1930:1933	arg1	inhibitors					1916:1925	specific inhibitors	1907:1925	specific inhibitors of PI3K (Wortmannin and LY294002)	1907:1959	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	7	88	theme	NE	1222:1223	arg1	rats					1226:1229	5/6 nephrectomized (NE) rats	1202:1229	5/6 nephrectomized (NE) rats	1202:1229	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	11	89	theme	specific	1907:1914	arg1	LY294002					1951:1958	LY294002	1951:1958	LY294002	1951:1958	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	11	89	theme	specific	1907:1914	arg1	Wortmannin					1936:1945	Wortmannin	1936:1945	Wortmannin	1936:1945	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	11	89	theme	specific	1907:1914	arg1	inhibitors					1916:1925	specific inhibitors	1907:1925	specific inhibitors of PI3K (Wortmannin and LY294002)	1907:1959	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	7	90	theme	nephrectomized	1206:1219	arg1	rats					1226:1229	5/6 nephrectomized (NE) rats	1202:1229	5/6 nephrectomized (NE) rats	1202:1229	We used a novel and reliable CI-AKI model consisting of 5/6 nephrectomized (NE) rats, and a low-osmolar contrast media (iohexol, 10mL/kg, 3.5gI) injected via the tail vein after dehydration for 48h.
28017896	11	91	theme	signaling	2018:2026	arg1	pathway					2028:2034	Akt signaling pathway	2014:2034	Akt signaling pathway	2014:2034	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	10	92	theme	caspase-3	1879:1887	arg1	levels					1853:1858	the levels	1849:1858	the levels of Bax and cleaved caspase-3	1849:1887	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	10	93	theme	expression	1732:1741	arg1	levels					1743:1748	the protein expression levels	1720:1748	the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2	1720:1832	Augmented O-GlcNAc signaling also increased the protein expression levels of phospho-Akt (Ser473, but not Thr308 and Thr450), phospho-GSK-3β, Nrf2, and Bcl-2, and decreased the levels of Bax and cleaved caspase-3.
28017896	5	94	theme	augmented	836:844	arg1	signaling					854:862	augmented OGlcNAc signaling	836:862	augmented OGlcNAc signaling	836:862	However, the underlying mechanisms by which augmented OGlcNAc signaling provides renoprotection against contrast media insults is still unknown.
28017896	9	95	theme	transferase	1653:1663	arg1	inhibitor					1665:1673	an O-GlcNAc transferase inhibitor	1641:1673	an O-GlcNAc transferase inhibitor	1641:1673	Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor.
28017896	9	95	theme	transferase	1653:1663	arg1	alloxan					1632:1638	alloxan	1632:1638	alloxan	1632:1638	Furthermore, this renoprotection was blocked by treatment with alloxan, an O-GlcNAc transferase inhibitor.
28017896	3	96	theme	regulatory	517:526	arg1	β-N-acetylglucosamine					460:480	O-linked β-N-acetylglucosamine	451:480	O-linked β-N-acetylglucosamine (O-GlcNAc)	451:491	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	96	theme	regulatory	517:526	arg1	modification					528:539	a post-translational regulatory modification	496:539	a post-translational regulatory modification of intracellular proteins	496:565	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	11	97	theme	glucosamine	1987:1997	arg1	protection					1973:1982	the protection	1969:1982	the protection of glucosamine	1969:1997	Both alloxan and specific inhibitors of PI3K (Wortmannin and LY294002) blocked the protection of glucosamine via inhibiting Akt signaling pathway.
28017896	4	98	theme	Increasing	642:651	arg1	evidence					653:660	Increasing evidence	642:660	Increasing evidence	642:660	Increasing evidence suggests that O-GlcNAc levels are increased in response to stress and that acute augmentation of this reaction is cytoprotective.
28017896	2	99	theme	agents	343:348	arg1	agents					343:348	agents	343:348	agents for renal protection	343:369	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	2	99	theme	agents	343:348	arg1	variety					332:338	a variety	330:338	a variety of agents for renal protection	330:369	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	1	100	theme	substantial	239:249	arg1	morbidity					251:259	morbidity	251:259	morbidity	251:259	Contrast-induced acute kidney injury (CI-AKI) is an iatrogenic renal injury and associated with substantial morbidity and mortality in susceptible individuals.
28017896	12	101	theme	O-GlcNAcylated	2059:2072	arg1	Akt					2074:2076	O-GlcNAcylated Akt	2059:2076	O-GlcNAcylated Akt	2059:2076	We further identified O-GlcNAcylated Akt through immunoprecipitation and western blot.
28017896	2	102	from	effective	413:421	arg1	reduction					430:438	the reduction	426:438	the reduction of CI-AKI	426:448	Despite extensive study of a variety of agents for renal protection, limited strategies have been shown to be effective in the reduction of CI-AKI.
28017896	6	103	from	effect	963:968	arg1	CI-AKI					1021:1026	CI-AKI	1021:1026	CI-AKI	1021:1026	Here, we investigated the effect of augmented O-GlcNAc signaling via glucosamine on CI-AKI and explored the underlying molecular mechanisms, particularly its relationship with PI3-kinase (PI3K)/Akt signaling.
28017896	3	104	theme	proteins	558:565	arg1	β-N-acetylglucosamine					460:480	O-linked β-N-acetylglucosamine	451:480	O-linked β-N-acetylglucosamine (O-GlcNAc)	451:491	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
28017896	3	104	theme	proteins	558:565	arg1	modification					528:539	a post-translational regulatory modification	496:539	a post-translational regulatory modification of intracellular proteins	496:565	O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational regulatory modification of intracellular proteins and governs the function of numerous proteins, both cytosolic and nuclear.
30786250	10	0	theme	5-aminoimidazole-4-carboxamide	1483:1512	arg1	ribose					1514:1519	5-aminoimidazole-4-carboxamide ribose	1483:1519	5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator)	1483:1546	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	1	dep	acid	1566:1569	arg1	inhibitor					1592:1600	an ER stress inhibitor	1579:1600	an ER stress inhibitor	1579:1600	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	1	dep	acid	1566:1569	arg1	4-PBA					1572:1576	4-PBA	1572:1576	4-PBA	1572:1576	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	2	theme	GFAT	1640:1643	arg1	antagonist					1645:1654	a GFAT antagonist	1638:1654	a GFAT antagonist	1638:1654	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	2	theme	GFAT	1640:1643	arg1	DON					1633:1635	DON	1633:1635	DON	1633:1635	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	9	3	theme	selective	1395:1403	arg1	4-DAMP					1385:1390	4-DAMP	1385:1390	4-DAMP	1385:1390	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	3	theme	selective	1395:1403	arg1	antagonist					1413:1422	a selective M3 AChR antagonist	1393:1422	a selective M3 AChR antagonist	1393:1422	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	10	4	theme	AMPK	1532:1535	arg1	AICAR					1522:1526	AICAR	1522:1526	AICAR	1522:1526	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	4	theme	AMPK	1532:1535	arg1	activator					1537:1545	an AMPK activator	1529:1545	an AMPK activator	1529:1545	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	2	5	theme	pathway	340:346	arg1	flux					354:357	hexosamine biosynthetic pathway (HBP) flux	316:357	hexosamine biosynthetic pathway (HBP) flux	316:357	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	9	6	theme	AChR	1408:1411	arg1	4-DAMP					1385:1390	4-DAMP	1385:1390	4-DAMP	1385:1390	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	6	theme	AChR	1408:1411	arg1	antagonist					1413:1422	a selective M3 AChR antagonist	1393:1422	a selective M3 AChR antagonist	1393:1422	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	2	7	theme	hexosamine	316:325	arg1	pathway					340:346	hexosamine biosynthetic pathway	316:346	hexosamine biosynthetic pathway (HBP) flux	316:357	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	2	7	theme	hexosamine	316:325	arg1	HBP					349:351	HBP	349:351	HBP	349:351	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	10	8	theme	4-phenyl	1549:1556	arg1	acid					1566:1569	4-phenyl butyric acid	1549:1569	4-phenyl butyric acid (4-PBA, an ER stress inhibitor)	1549:1601	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	11	9	theme	signaling	1734:1742	arg1	Activation					1708:1717	SIGNIFICANCE Activation	1695:1717	SIGNIFICANCE Activation of cholinergic signaling	1695:1742	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	7	10	theme	AMP-activated	1099:1111	arg1	AMPK					1129:1132	AMPK	1129:1132	AMPK	1129:1132	Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK).
30786250	7	10	theme	AMP-activated	1099:1111	arg1	kinase					1121:1126	phosphorylated AMP-activated protein kinase	1084:1126	phosphorylated AMP-activated protein kinase (AMPK)	1084:1133	Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK).
30786250	6	11	theme	reticulum	936:944	arg1	stress					951:956	endoplasmic reticulum (ER) stress	924:956	endoplasmic reticulum (ER) stress	924:956	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	4	12	theme	umbilical	619:627	arg1	HUVECs					653:658	HUVECs	653:658	HUVECs	653:658	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	12	theme	umbilical	619:627	arg1	cells					646:650	human umbilical vein endothelial cells	613:650	in vitro human umbilical vein endothelial cells (HUVECs)	604:659	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	13	theme	diet	473:476	arg1	model					484:488	High fat diet (HFD) model	464:488	High fat diet (HFD) model	464:488	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	14	theme	endothelial	634:644	arg1	HUVECs					653:658	HUVECs	653:658	HUVECs	653:658	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	14	theme	endothelial	634:644	arg1	cells					646:650	human umbilical vein endothelial cells	613:650	in vitro human umbilical vein endothelial cells (HUVECs)	604:659	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	6	15	theme	HG	904:905	arg1	addition					907:914	HG addition	904:914	HG addition	904:914	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	11	16	theme	endothelium	1756:1766	arg1	damage					1768:1773	endothelium damage	1756:1773	endothelium damage	1756:1773	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	4	17	theme	MAIN	451:454	arg1	METHODS					456:462	MAIN METHODS	451:462	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).	451:738	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	5	18	theme	HFD-fed	890:896	arg1	mice					898:901	HFD-fed mice	890:901	HFD-fed mice	890:901	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	4	19	theme	High	464:467	arg1	HFD					479:481	HFD	479:481	HFD	479:481	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	19	theme	High	464:467	arg1	diet					473:476	High fat diet	464:476	High fat diet (HFD) model	464:488	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	11	20	theme	M3	1906:1907	arg1	signaling					1919:1927	M3 AChR-AMPK signaling	1906:1927	M3 AChR-AMPK signaling	1906:1927	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	4	21	theme	high	678:681	arg1	HG					692:693	HG	692:693	HG	692:693	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	21	theme	high	678:681	arg1	glucose					683:689	high glucose	678:689	high glucose (HG, 30 mM)	678:701	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	11	22	theme	SIGNIFICANCE	1695:1706	arg1	Activation					1708:1717	SIGNIFICANCE Activation	1695:1717	SIGNIFICANCE Activation of cholinergic signaling	1695:1742	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	0	23	theme	AChR-AMPK-ER	90:101	arg1	signaling					110:118	M3 AChR-AMPK-ER stress signaling	87:118	M3 AChR-AMPK-ER stress signaling	87:118	Cholinergic drugs ameliorate endothelial dysfunction by decreasing O-GlcNAcylation via M3 AChR-AMPK-ER stress signaling.
30786250	9	24	theme	ER	1255:1256	arg1	stress					1258:1263	HG-induced ER stress	1244:1263	HG-induced ER stress	1244:1263	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	5	25	theme	endothelial	858:868	arg1	cells					870:874	vascular endothelial cells	849:874	vascular endothelial cells detachment in HFD-fed mice	849:901	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	11	26	from	O-GlcNAcylation	1805:1819	arg1	mice					1839:1842	mice	1839:1842	mice	1839:1842	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	11	26	from	O-GlcNAcylation	1805:1819	arg1	HUVECs					1848:1853	HUVECs	1848:1853	HUVECs	1848:1853	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	1	27	theme	increased	153:161	arg1	morbidity					178:186	morbidity	178:186	morbidity	178:186	AIMS Obesity is associated with increased cardiovascular morbidity and mortality.
30786250	10	28	theme	ER	1582:1583	arg1	inhibitor					1592:1600	an ER stress inhibitor	1579:1600	an ER stress inhibitor	1579:1600	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	28	theme	ER	1582:1583	arg1	4-PBA					1572:1576	4-PBA	1572:1576	4-PBA	1572:1576	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	0	29	theme	Cholinergic	0:10	arg1	drugs					12:16	Cholinergic drugs	0:16	Cholinergic drugs	0:16	Cholinergic drugs ameliorate endothelial dysfunction by decreasing O-GlcNAcylation via M3 AChR-AMPK-ER stress signaling.
30786250	4	30	dep	HG	692:693	arg1	30 mM					696:700	30 mM	696:700	30 mM	696:700	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	3	31	theme	O-GlcNAc	403:410	arg1	levels					412:417	the O-GlcNAc levels	399:417	the O-GlcNAc levels induced by obesity	399:436	However, the changes and regulation of the O-GlcNAc levels induced by obesity are unclear.
30786250	11	32	theme	obese	1861:1865	arg1	conditions					1867:1876	obese conditions	1861:1876	obese conditions	1861:1876	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	5	33	theme	body	779:782	arg1	weight					784:789	body weight	779:789	body weight	779:789	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	10	34	theme	similar	1670:1676	arg1	effect					1678:1683	a similar effect	1668:1683	a similar effect	1668:1683	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	35	dep	6-diazo-5-oxonorleucine	1608:1630	arg1	antagonist					1645:1654	a GFAT antagonist	1638:1654	a GFAT antagonist	1638:1654	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	35	dep	6-diazo-5-oxonorleucine	1608:1630	arg1	DON					1633:1635	DON	1633:1635	DON	1633:1635	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	11	36	theme	ER	1794:1795	arg1	stress					1797:1802	ER stress	1794:1802	ER stress	1794:1802	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	7	37	theme	kinase	1121:1126	arg1	levels					1074:1079	levels	1074:1079	levels of phosphorylated AMP-activated protein kinase (AMPK)	1074:1133	Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK).
30786250	4	38	theme	cholinergic	538:548	arg1	PYR					571:573	PYR	571:573	PYR	571:573	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	38	theme	cholinergic	538:548	arg1	pyridostigmine					555:568	the cholinergic drug pyridostigmine	534:568	the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks	534:598	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	2	39	theme	O-linked	234:241	arg1	modification					276:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	9	40	dep	C	1437:1437	arg1	inhibitor					1456:1464	an AMPK inhibitor	1448:1464	an AMPK inhibitor	1448:1464	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	40	dep	C	1437:1437	arg1	C					1445:1445	Comp C	1440:1445	Comp C	1440:1445	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	4	41	dep	METHODS	456:462	arg1	induced					494:500	induced	494:500	was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh)	490:737	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	7	42	theme	protein	1113:1119	arg1	AMPK					1129:1132	AMPK	1129:1132	AMPK	1129:1132	Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK).
30786250	7	42	theme	protein	1113:1119	arg1	kinase					1121:1126	phosphorylated AMP-activated protein kinase	1084:1126	phosphorylated AMP-activated protein kinase (AMPK)	1084:1133	Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK).
30786250	4	43	theme	in	604:605	arg1	HUVECs					653:658	HUVECs	653:658	HUVECs	653:658	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	43	theme	in	604:605	arg1	cells					646:650	human umbilical vein endothelial cells	613:650	in vitro human umbilical vein endothelial cells (HUVECs)	604:659	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	7	44	theme	phosphorylated	1084:1097	arg1	AMPK					1129:1132	AMPK	1129:1132	AMPK	1129:1132	Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK).
30786250	7	44	theme	phosphorylated	1084:1097	arg1	kinase					1121:1126	phosphorylated AMP-activated protein kinase	1084:1126	phosphorylated AMP-activated protein kinase (AMPK)	1084:1133	Additionally, HG decreased levels of phosphorylated AMP-activated protein kinase (AMPK).
30786250	9	45	from	effects	1226:1232	arg1	O-GlcNAcylation					1266:1280	O-GlcNAcylation	1266:1280	O-GlcNAcylation	1266:1280	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	45	from	effects	1226:1232	arg1	apoptosis					1287:1295	apoptosis	1287:1295	apoptosis	1287:1295	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	45	from	effects	1226:1232	arg1	stress					1258:1263	HG-induced ER stress	1244:1263	HG-induced ER stress	1244:1263	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	11	46	from	damage	1768:1773	arg1	mice					1839:1842	mice	1839:1842	mice	1839:1842	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	11	46	from	damage	1768:1773	arg1	HUVECs					1848:1853	HUVECs	1848:1853	HUVECs	1848:1853	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	9	47	theme	M3	1405:1406	arg1	4-DAMP					1385:1390	4-DAMP	1385:1390	4-DAMP	1385:1390	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	47	theme	M3	1405:1406	arg1	antagonist					1413:1422	a selective M3 AChR antagonist	1393:1422	a selective M3 AChR antagonist	1393:1422	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	4	48	from	obesity	502:508	arg1	mice					513:516	mice	513:516	mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs)	513:659	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	2	49	theme	biosynthetic	327:338	arg1	pathway					340:346	hexosamine biosynthetic pathway	316:346	hexosamine biosynthetic pathway (HBP) flux	316:357	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	2	49	theme	biosynthetic	327:338	arg1	HBP					349:351	HBP	349:351	HBP	349:351	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	5	50	theme	FINDINGS	744:751	arg1	PYR					753:755	KEY FINDINGS PYR	740:755	KEY FINDINGS PYR	740:755	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	10	51	theme	butyric	1558:1564	arg1	acid					1566:1569	4-phenyl butyric acid	1549:1569	4-phenyl butyric acid (4-PBA, an ER stress inhibitor)	1549:1601	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	6	52	from	apoptosis	999:1007	arg1	HUVECs					1012:1017	HUVECs	1012:1017	HUVECs	1012:1017	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	5	53	theme	O-GlcNAcylation	811:825	arg1	levels					827:832	O-GlcNAcylation levels	811:832	O-GlcNAcylation levels	811:832	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	6	54	theme	endoplasmic	924:934	arg1	ER					947:948	ER	947:948	ER	947:948	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	6	54	theme	endoplasmic	924:934	arg1	reticulum					936:944	endoplasmic reticulum	924:944	endoplasmic reticulum (ER) stress	924:956	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	4	55	theme	human	613:617	arg1	HUVECs					653:658	HUVECs	653:658	HUVECs	653:658	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	55	theme	human	613:617	arg1	cells					646:650	human umbilical vein endothelial cells	613:650	in vitro human umbilical vein endothelial cells (HUVECs)	604:659	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	11	56	theme	cholinergic	1722:1732	arg1	signaling					1734:1742	cholinergic signaling	1722:1742	cholinergic signaling	1722:1742	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	9	57	theme	compound	1428:1435	arg1	C					1437:1437	compound C	1428:1437	compound C (Comp C, an AMPK inhibitor)	1428:1465	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	58	theme	Comp	1440:1443	arg1	inhibitor					1456:1464	an AMPK inhibitor	1448:1464	an AMPK inhibitor	1448:1464	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	58	theme	Comp	1440:1443	arg1	C					1445:1445	Comp C	1440:1445	Comp C	1440:1445	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	59	dep	methiodide	1373:1382	arg1	4-DAMP					1385:1390	4-DAMP	1385:1390	4-DAMP	1385:1390	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	59	dep	methiodide	1373:1382	arg1	antagonist					1413:1422	a selective M3 AChR antagonist	1393:1422	a selective M3 AChR antagonist	1393:1422	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	4	60	theme	vein	629:632	arg1	HUVECs					653:658	HUVECs	653:658	HUVECs	653:658	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	60	theme	vein	629:632	arg1	cells					646:650	human umbilical vein endothelial cells	613:650	in vitro human umbilical vein endothelial cells (HUVECs)	604:659	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	11	61	theme	reduced	1776:1782	arg1	levels					1784:1789	reduced levels	1776:1789	reduced levels of ER stress	1776:1802	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	10	62	dep	ribose	1514:1519	arg1	AICAR					1522:1526	AICAR	1522:1526	AICAR	1522:1526	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	62	dep	ribose	1514:1519	arg1	activator					1537:1545	an AMPK activator	1529:1545	an AMPK activator	1529:1545	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	2	63	theme	O-GlcNAc	266:273	arg1	modification					276:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	5	64	theme	cells	870:874	arg1	detachment					876:885	vascular endothelial cells detachment	849:885	vascular endothelial cells detachment in HFD-fed mice	849:901	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	4	65	dep	in	604:605	arg1	vitro					607:611	vitro	607:611	vitro	607:611	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	11	66	theme	AChR-AMPK	1909:1917	arg1	signaling					1919:1927	M3 AChR-AMPK signaling	1906:1927	M3 AChR-AMPK signaling	1906:1927	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	2	67	mod	modification	276:287	arg1	proteins					292:299	proteins	292:299	proteins	292:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	2	67	mod	modification	276:287	arg3	O-GlcNAc					266:273	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	2	67	mod	modification	276:287	arg3	β-N-acetylglucosamine					243:263	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	9	68	theme	AMPK	1451:1454	arg1	inhibitor					1456:1464	an AMPK inhibitor	1448:1464	an AMPK inhibitor	1448:1464	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	9	68	theme	AMPK	1451:1454	arg1	C					1445:1445	Comp C	1440:1445	Comp C	1440:1445	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	4	69	theme	fat	469:471	arg1	HFD					479:481	HFD	479:481	HFD	479:481	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	69	theme	fat	469:471	arg1	diet					473:476	High fat diet	464:476	High fat diet (HFD) model	464:488	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	11	70	from	apoptosis	1826:1834	arg1	mice					1839:1842	mice	1839:1842	mice	1839:1842	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	11	70	from	apoptosis	1826:1834	arg1	HUVECs					1848:1853	HUVECs	1848:1853	HUVECs	1848:1853	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	0	71	theme	M3	87:88	arg1	signaling					110:118	M3 AChR-AMPK-ER stress signaling	87:118	M3 AChR-AMPK-ER stress signaling	87:118	Cholinergic drugs ameliorate endothelial dysfunction by decreasing O-GlcNAcylation via M3 AChR-AMPK-ER stress signaling.
30786250	9	72	theme	ACh	1237:1239	arg1	effects					1226:1232	the effects	1222:1232	the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis	1222:1295	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	2	73	theme	proteins	292:299	arg1	modification					276:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	1	74	theme	cardiovascular	163:176	arg1	morbidity					178:186	morbidity	178:186	morbidity	178:186	AIMS Obesity is associated with increased cardiovascular morbidity and mortality.
30786250	6	75	theme	O-GlcNAcylation	972:986	arg1	levels					988:993	O-GlcNAcylation levels	972:993	O-GlcNAcylation levels	972:993	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	0	76	theme	stress	103:108	arg1	signaling					110:118	M3 AChR-AMPK-ER stress signaling	87:118	M3 AChR-AMPK-ER stress signaling	87:118	Cholinergic drugs ameliorate endothelial dysfunction by decreasing O-GlcNAcylation via M3 AChR-AMPK-ER stress signaling.
30786250	9	77	theme	HG-induced	1244:1253	arg1	stress					1258:1263	HG-induced ER stress	1244:1263	HG-induced ER stress	1244:1263	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	5	78	theme	vascular	849:856	arg1	cells					870:874	vascular endothelial cells	849:874	vascular endothelial cells detachment in HFD-fed mice	849:901	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	11	79	dep	ameliorated	1744:1754	arg1	function					1889:1896	function	1889:1896	may function through M3 AChR-AMPK signaling	1885:1927	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	10	80	with	Treatment	1468:1476	arg1	ribose					1514:1519	5-aminoimidazole-4-carboxamide ribose	1483:1519	5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator)	1483:1546	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	80	with	Treatment	1468:1476	arg1	acid					1566:1569	4-phenyl butyric acid	1549:1569	4-phenyl butyric acid (4-PBA, an ER stress inhibitor)	1549:1601	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	80	with	Treatment	1468:1476	arg1	6-diazo-5-oxonorleucine					1608:1630	6-diazo-5-oxonorleucine	1608:1630	6-diazo-5-oxonorleucine (DON, a GFAT antagonist)	1608:1655	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	6	81	from	levels	988:993	arg1	HUVECs					1012:1017	HUVECs	1012:1017	HUVECs	1012:1017	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	4	82	dep	PYR	571:573	arg1	3 mg/kg/d					576:584	3 mg/kg/d	576:584	3 mg/kg/d	576:584	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	11	83	from	levels	1784:1789	arg1	mice					1839:1842	mice	1839:1842	mice	1839:1842	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	11	83	from	levels	1784:1789	arg1	HUVECs					1848:1853	HUVECs	1848:1853	HUVECs	1848:1853	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	10	84	theme	stress	1585:1590	arg1	inhibitor					1592:1600	an ER stress inhibitor	1579:1600	an ER stress inhibitor	1579:1600	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	10	84	theme	stress	1585:1590	arg1	4-PBA					1572:1576	4-PBA	1572:1576	4-PBA	1572:1576	Treatment with 5-aminoimidazole-4-carboxamide ribose (AICAR, an AMPK activator), 4-phenyl butyric acid (4-PBA, an ER stress inhibitor), and 6-diazo-5-oxonorleucine (DON, a GFAT antagonist) reproduced a similar effect with ACh.
30786250	6	85	theme	time-dependent	1024:1037	arg1	manner					1039:1044	a time-dependent manner	1022:1044	a time-dependent manner	1022:1044	HG addition induced endoplasmic reticulum (ER) stress and increased O-GlcNAcylation levels and apoptosis in HUVECs in a time-dependent manner.
30786250	0	86	theme	endothelial	29:39	arg1	dysfunction					41:51	endothelial dysfunction	29:51	endothelial dysfunction	29:51	Cholinergic drugs ameliorate endothelial dysfunction by decreasing O-GlcNAcylation via M3 AChR-AMPK-ER stress signaling.
30786250	5	87	from	detachment	876:885	arg1	mice					898:901	HFD-fed mice	890:901	HFD-fed mice	890:901	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	1	88	theme	AIMS	121:124	arg1	Obesity					126:132	AIMS Obesity	121:132	AIMS Obesity	121:132	AIMS Obesity is associated with increased cardiovascular morbidity and mortality.
30786250	3	89	theme	levels	412:417	arg1	regulation					385:394	regulation	385:394	regulation	385:394	However, the changes and regulation of the O-GlcNAc levels induced by obesity are unclear.
30786250	3	89	theme	levels	412:417	arg1	changes					373:379	changes	373:379	changes	373:379	However, the changes and regulation of the O-GlcNAc levels induced by obesity are unclear.
30786250	5	90	theme	blood	792:796	arg1	glucose					798:804	blood glucose	792:804	blood glucose	792:804	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	3	91	dep	changes	373:379	arg1	the					369:371	the	369:371	the	369:371	However, the changes and regulation of the O-GlcNAc levels induced by obesity are unclear.
30786250	2	92	link	O-linked	234:241	arg1	modification					276:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	5	93	theme	KEY	740:742	arg1	FINDINGS					744:751	KEY FINDINGS	740:751	KEY FINDINGS PYR	740:755	KEY FINDINGS PYR significantly reduced body weight, blood glucose, and O-GlcNAcylation levels and attenuated vascular endothelial cells detachment in HFD-fed mice.
30786250	4	94	theme	drug	550:553	arg1	PYR					571:573	PYR	571:573	PYR	571:573	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	4	94	theme	drug	550:553	arg1	pyridostigmine					555:568	the cholinergic drug pyridostigmine	534:568	the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks	534:598	MAIN METHODS High fat diet (HFD) model was induced obesity in mice with or without the cholinergic drug pyridostigmine (PYR, 3 mg/kg/d) for 22 weeks and in vitro human umbilical vein endothelial cells (HUVECs) was treated with high glucose (HG, 30 mM) with or without acetylcholine (ACh).
30786250	2	95	theme	β-N-acetylglucosamine	243:263	arg1	modification					276:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
30786250	11	96	theme	stress	1797:1802	arg1	damage					1768:1773	endothelium damage	1756:1773	endothelium damage	1756:1773	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	11	96	theme	stress	1797:1802	arg1	levels					1784:1789	reduced levels	1776:1789	reduced levels of ER stress	1776:1802	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	11	96	theme	stress	1797:1802	arg1	apoptosis					1826:1834	apoptosis	1826:1834	apoptosis	1826:1834	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	11	96	theme	stress	1797:1802	arg1	O-GlcNAcylation					1805:1819	O-GlcNAcylation	1805:1819	O-GlcNAcylation	1805:1819	SIGNIFICANCE Activation of cholinergic signaling ameliorated endothelium damage, reduced levels of ER stress, O-GlcNAcylation, and apoptosis in mice and HUVECs under obese conditions, which may function through M3 AChR-AMPK signaling.
30786250	9	97	theme	4-diphenylacetoxy-N-methylpiperidine	1336:1371	arg1	methiodide					1373:1382	4-diphenylacetoxy-N-methylpiperidine methiodide	1336:1382	4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist)	1336:1423	Furthermore, the effects of ACh on HG-induced ER stress, O-GlcNAcylation, and apoptosis were prevented by treating HUVECs with 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, a selective M3 AChR antagonist) or compound C (Comp C, an AMPK inhibitor).
30786250	2	98	theme	augmented	224:232	arg1	modification					276:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification	224:287	augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins	224:299	It is accompanied by augmented O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins via increasing hexosamine biosynthetic pathway (HBP) flux.
28302723	10	0	from	OGT	1738:1740	arg1	consequences					1689:1700	the molecular consequences	1675:1700	the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism	1675:1780	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	1	1	theme	multiple	295:302	arg1	transcription					336:348	transcription	336:348	transcription	336:348	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	1	1	theme	multiple	295:302	arg1	processes					315:323	multiple biological processes	295:323	multiple biological processes	295:323	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	11	2	theme	proteins	2084:2091	arg1	modification					2046:2057	the O-GlcNAc post-translational modification	2014:2057	the O-GlcNAc post-translational modification of nuclear and cytosolic proteins	2014:2091	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	3	3	theme	affected	686:693	arg1	family					695:700	an affected family	683:700	an affected family	683:700	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	9	4	theme	transcriptome	1501:1513	arg1	analysis					1515:1522	Global transcriptome analysis	1494:1522	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls	1494:1574	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls revealed a small subset of genes that are differentially expressed.
28302723	4	5	theme	molecular	843:851	arg1	experiments					862:872	molecular modeling experiments	843:872	molecular modeling experiments	843:872	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	1	6	theme	post-translational	205:222	arg1	modification					224:235	a regulatory post-translational modification	192:235	a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription	192:348	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	1	6	theme	post-translational	205:222	arg1	O-GlcNAc					180:187	O-GlcNAc	180:187	O-GlcNAc	180:187	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	10	7	theme	affected	1824:1831	arg1	individuals					1833:1843	affected individuals	1824:1843	affected individuals	1824:1843	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	9	8	theme	lymphoblastoids	1537:1551	arg1	analysis					1515:1522	Global transcriptome analysis	1494:1522	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls	1494:1574	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls revealed a small subset of genes that are differentially expressed.
28302723	10	9	theme	O-GlcNAc	1871:1878	arg1	levels					1880:1885	steady-state O-GlcNAc levels	1858:1885	steady-state O-GlcNAc levels	1858:1885	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	4	10	from	individuals	814:824	arg1	lines					794:798	isolated lymphoblastoid cell lines	765:798	isolated lymphoblastoid cell lines from affected individuals	765:824	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	1	11	theme	proteins	258:265	arg1	modification					224:235	a regulatory post-translational modification	192:235	a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription	192:348	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	1	11	theme	proteins	258:265	arg1	O-GlcNAc					180:187	O-GlcNAc	180:187	O-GlcNAc	180:187	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	7	12	from	decrease	1235:1242	arg1	levels					1281:1286	steady-state OGA protein and mRNA levels	1247:1286	levels	1281:1286	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	7	12	from	decrease	1235:1242	arg1	protein					1264:1270	steady-state OGA protein and mRNA levels	1247:1286	protein	1264:1270	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	10	13	theme	molecular	1679:1687	arg1	consequences					1689:1700	the molecular consequences	1675:1700	the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism	1675:1780	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	0	14	theme	intellectual	155:166	arg1	disability					168:177	X-linked intellectual disability	146:177	X-linked intellectual disability	146:177	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	2	15	dep	removal	442:448	arg1	OGA					464:466	OGA	464:466	OGA	464:466	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	2	15	dep	removal	442:448	arg1	O-GlcNAcase					451:461	O-GlcNAcase	451:461	O-GlcNAcase (OGA)	451:467	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	8	16	theme	transcriptional	1337:1351	arg1	mSin3A-HDAC1					1371:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	11	17	theme	cytosolic	2074:2082	arg1	proteins					2084:2091	nuclear and cytosolic proteins	2062:2091	nuclear and cytosolic proteins	2062:2091	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	9	18	theme	small	1587:1591	arg1	subset					1593:1598	a small subset	1585:1598	a small subset of genes that are differentially expressed	1585:1641	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls revealed a small subset of genes that are differentially expressed.
28302723	6	19	theme	OGT	1028:1030	arg1	levels					1032:1037	OGT levels	1028:1037	OGT levels seen in the L254F-OGT individual cells	1028:1076	Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered.
28302723	8	20	theme	complex	1363:1369	arg1	mSin3A-HDAC1					1371:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	11	21	theme	post-translational	2027:2044	arg1	modification					2046:2057	the O-GlcNAc post-translational modification	2014:2057	the O-GlcNAc post-translational modification of nuclear and cytosolic proteins	2014:2091	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	0	22	from	characterization	19:34	arg1	gene					120:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	0	23	theme	β-N-acetylglucosamine	75:95	arg1	gene					120:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	4	24	with	consistent	827:836	arg1	experiments					862:872	molecular modeling experiments	843:872	molecular modeling experiments	843:872	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	0	25	from	Identification	0:13	arg1	gene					120:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	2	26	dep	attachment	398:407	arg1	OGT					432:434	OGT	432:434	OGT	432:434	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	2	26	dep	attachment	398:407	arg1	transferase					419:429	O-GlcNAc transferase	410:429	O-GlcNAc transferase (OGT)	410:435	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	3	27	from	acid	555:558	arg1	repeat					585:590	the tetratricopeptide repeat	563:590	the tetratricopeptide repeat	563:590	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	0	28	link	X-linked	146:153	arg1	disability					168:177	X-linked intellectual disability	146:177	X-linked intellectual disability	146:177	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	0	29	from	mutation	50:57	arg1	gene					120:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	11	30	theme	OGT	1993:1995	arg1	OGT					1993:1995	OGT	1993:1995	OGT	1993:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	30	theme	OGT	1993:1995	arg1	domain					1982:1987	the tetratricopeptide repeat domain	1953:1987	the tetratricopeptide repeat domain	1953:1987	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	30	theme	OGT	1993:1995	arg1	domain					1945:1950	the regulatory domain	1930:1950	the regulatory domain (the tetratricopeptide repeat domain) of OGT	1930:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	31	theme	tetratricopeptide	1957:1973	arg1	OGT					1993:1995	OGT	1993:1995	OGT	1993:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	31	theme	tetratricopeptide	1957:1973	arg1	domain					1982:1987	the tetratricopeptide repeat domain	1953:1987	the tetratricopeptide repeat domain	1953:1987	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	31	theme	tetratricopeptide	1957:1973	arg1	domain					1945:1950	the regulatory domain	1930:1950	the regulatory domain (the tetratricopeptide repeat domain) of OGT	1930:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	0	32	theme	transferase	108:118	arg1	gene					120:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	5	33	theme	HCF-1	987:991	arg1	protease					993:1000	an HCF-1 protease	984:1000	an HCF-1 protease	984:1000	Recombinant expression of L254F-OGT demonstrated that the enzyme is active as both a glycosyltransferase and an HCF-1 protease.
28302723	7	34	from	individuals	1204:1214	arg1	lymphoblastoids					1174:1188	lymphoblastoids	1174:1188	lymphoblastoids from affected individuals	1174:1214	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	0	35	theme	O-linked	66:73	arg1	β-N-acetylglucosamine					75:95	O-linked β-N-acetylglucosamine	66:95	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	0	35	theme	O-linked	66:73	arg1	O-GlcNAc					98:105	O-GlcNAc	98:105	O-GlcNAc	98:105	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	8	36	theme	OGA	1419:1421	arg1	region					1409:1414	the proximal promoter region	1387:1414	the proximal promoter region of OGA	1387:1421	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	6	37	theme	individual	1061:1070	arg1	cells					1072:1076	the L254F-OGT individual cells	1047:1076	the L254F-OGT individual cells	1047:1076	Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered.
28302723	11	38	from	substitution	1914:1925	arg1	OGT					1993:1995	OGT	1993:1995	OGT	1993:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	38	from	substitution	1914:1925	arg1	domain					1982:1987	the tetratricopeptide repeat domain	1953:1987	the tetratricopeptide repeat domain	1953:1987	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	38	from	substitution	1914:1925	arg1	domain					1945:1950	the regulatory domain	1930:1950	the regulatory domain (the tetratricopeptide repeat domain) of OGT	1930:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	4	39	theme	OGT	730:732	arg1	levels					742:747	steady-state OGT protein levels	717:747	steady-state OGT protein levels	717:747	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	4	40	located	observed	753:760	arg2	decrease					705:712	A decrease	703:712	A decrease in steady-state OGT protein levels	703:747	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	4	40	located	observed	753:760	arg1	lines					794:798	isolated lymphoblastoid cell lines	765:798	isolated lymphoblastoid cell lines from affected individuals	765:824	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	8	41	theme	OGA	1453:1455	arg1	activity					1466:1473	OGA promoter activity	1453:1473	OGA promoter activity	1453:1473	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	11	42	theme	acid	1909:1912	arg1	substitution					1914:1925	a single amino acid substitution	1894:1925	a single amino acid substitution	1894:1925	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	0	43	theme	mutation	50:57	arg1	characterization					19:34	characterization	19:34	characterization	19:34	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	0	43	theme	mutation	50:57	arg1	Identification					0:13	Identification	0:13	Identification	0:13	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	0	44	link	O-linked	66:73	arg1	β-N-acetylglucosamine					75:95	O-linked β-N-acetylglucosamine	66:95	the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene	62:123	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	0	44	link	O-linked	66:73	arg1	O-GlcNAc					98:105	O-GlcNAc	98:105	O-GlcNAc	98:105	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	3	45	link	X-linked	640:647	arg1	XLID					674:677	XLID	674:677	XLID	674:677	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	45	link	X-linked	640:647	arg1	disability					662:671	X-linked intellectual disability	640:671	X-linked intellectual disability (XLID) in an affected family	640:700	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	8	46	theme	affected	1478:1485	arg1	cells					1487:1491	affected cells	1478:1491	affected cells	1478:1491	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	3	47	theme	exome	487:491	arg1	screen					493:498	An X-chromosome exome screen	471:498	An X-chromosome exome screen	471:498	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	6	48	theme	O-GlcNAc	1116:1123	arg1	levels					1125:1130	steady-state global O-GlcNAc levels	1096:1130	steady-state global O-GlcNAc levels	1096:1130	Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered.
28302723	3	49	theme	intellectual	649:660	arg1	XLID					674:677	XLID	674:677	XLID	674:677	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	49	theme	intellectual	649:660	arg1	disability					662:671	X-linked intellectual disability	640:671	X-linked intellectual disability (XLID) in an affected family	640:700	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	4	50	theme	cell	789:792	arg1	lines					794:798	isolated lymphoblastoid cell lines	765:798	isolated lymphoblastoid cell lines from affected individuals	765:824	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	2	51	theme	O-GlcNAc	410:417	arg1	OGT					432:434	OGT	432:434	OGT	432:434	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	2	51	theme	O-GlcNAc	410:417	arg1	transferase					419:429	O-GlcNAc transferase	410:429	O-GlcNAc transferase (OGT)	410:435	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	6	52	theme	steady-state	1096:1107	arg1	levels					1125:1130	steady-state global O-GlcNAc levels	1096:1130	steady-state global O-GlcNAc levels	1096:1130	Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered.
28302723	3	53	from	disability	662:671	arg1	family					695:700	an affected family	683:700	an affected family	683:700	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	54	theme	missense	513:520	arg1	mutation					522:529	a missense mutation	511:529	a missense mutation	511:529	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	54	theme	missense	513:520	arg1	acid					555:558	an amino acid	546:558	an amino acid in the tetratricopeptide repeat	546:590	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	4	55	theme	modeling	853:860	arg1	experiments					862:872	molecular modeling experiments	843:872	molecular modeling experiments	843:872	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	7	56	theme	mRNA	1276:1279	arg1	levels					1281:1286	steady-state OGA protein and mRNA levels	1247:1286	levels	1281:1286	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	3	57	theme	amino	549:553	arg1	mutation					522:529	a missense mutation	511:529	a missense mutation	511:529	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	57	theme	amino	549:553	arg1	acid					555:558	an amino acid	546:558	an amino acid in the tetratricopeptide repeat	546:590	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	1	58	theme	biological	304:313	arg1	transcription					336:348	transcription	336:348	transcription	336:348	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	1	58	theme	biological	304:313	arg1	processes					315:323	multiple biological processes	295:323	multiple biological processes	295:323	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	2	59	theme	single	362:367	arg1	enzymes					382:388	enzymes	382:388	enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA))	382:468	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	2	59	theme	single	362:367	arg1	genes					369:373	single genes	362:373	single genes	362:373	In humans, single genes encode enzymes for its attachment (O-GlcNAc transferase (OGT)) and removal (O-GlcNAcase (OGA)).
28302723	10	60	from	consequences	1689:1700	arg1	OGT					1738:1740	OGT	1738:1740	OGT	1738:1740	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	9	61	theme	genes	1603:1607	arg1	subset					1593:1598	a small subset	1585:1598	a small subset of genes that are differentially expressed	1585:1641	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls revealed a small subset of genes that are differentially expressed.
28302723	11	62	theme	nuclear	2062:2068	arg1	proteins					2084:2091	nuclear and cytosolic proteins	2062:2091	nuclear and cytosolic proteins	2062:2091	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	1	63	theme	regulatory	194:203	arg1	modification					224:235	a regulatory post-translational modification	192:235	a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription	192:348	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	1	63	theme	regulatory	194:203	arg1	O-GlcNAc					180:187	O-GlcNAc	180:187	O-GlcNAc	180:187	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	9	64	theme	Global	1494:1499	arg1	analysis					1515:1522	Global transcriptome analysis	1494:1522	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls	1494:1574	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls revealed a small subset of genes that are differentially expressed.
28302723	7	65	theme	steady-state	1247:1258	arg1	protein					1264:1270	steady-state OGA protein and mRNA levels	1247:1286	protein	1264:1270	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	3	66	theme	tetratricopeptide	567:583	arg1	repeat					585:590	the tetratricopeptide repeat	563:590	the tetratricopeptide repeat	563:590	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	67	dep	OGT	596:598	arg1	p.L254F					609:615	p.L254F	609:615	p.L254F	609:615	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	67	dep	OGT	596:598	arg1	759G>T					601:606	759G>T	601:606	759G>T (p.L254F)	601:616	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	8	68	theme	promoter	1457:1464	arg1	activity					1466:1473	OGA promoter activity	1453:1473	OGA promoter activity	1453:1473	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	10	69	theme	individuals	1833:1843	arg1	phenotype					1811:1819	the phenotype	1807:1819	the phenotype of affected individuals	1807:1843	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	9	70	theme	L254F-OGT	1527:1535	arg1	lymphoblastoids					1537:1551	L254F-OGT lymphoblastoids	1527:1551	L254F-OGT lymphoblastoids compared with controls	1527:1574	Global transcriptome analysis of L254F-OGT lymphoblastoids compared with controls revealed a small subset of genes that are differentially expressed.
28302723	0	71	theme	X-linked	146:153	arg1	disability					168:177	X-linked intellectual disability	146:177	X-linked intellectual disability	146:177	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	5	72	theme	Recombinant	875:885	arg1	expression					887:896	Recombinant expression	875:896	Recombinant expression of L254F-OGT	875:909	Recombinant expression of L254F-OGT demonstrated that the enzyme is active as both a glycosyltransferase and an HCF-1 protease.
28302723	1	73	theme	nucleocytoplasmic	240:256	arg1	proteins					258:265	nucleocytoplasmic proteins	240:265	nucleocytoplasmic proteins	240:265	O-GlcNAc is a regulatory post-translational modification of nucleocytoplasmic proteins that has been implicated in multiple biological processes, including transcription.
28302723	10	74	theme	steady-state	1858:1869	arg1	levels					1880:1885	steady-state O-GlcNAc levels	1858:1885	steady-state O-GlcNAc levels	1858:1885	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	0	75	from	gene	120:123	arg1	characterization					19:34	characterization	19:34	characterization	19:34	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	0	75	from	gene	120:123	arg1	Identification					0:13	Identification	0:13	Identification	0:13	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	4	76	theme	isolated	765:772	arg1	lines					794:798	isolated lymphoblastoid cell lines	765:798	isolated lymphoblastoid cell lines from affected individuals	765:824	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	8	77	theme	proximal	1391:1398	arg1	region					1409:1414	the proximal promoter region	1387:1414	the proximal promoter region of OGA	1387:1421	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	8	78	theme	OGT-containing	1322:1335	arg1	mSin3A-HDAC1					1371:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	11	79	theme	single	1896:1901	arg1	substitution					1914:1925	a single amino acid substitution	1894:1925	a single amino acid substitution	1894:1925	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	7	80	theme	OGA	1260:1262	arg1	protein					1264:1270	steady-state OGA protein and mRNA levels	1247:1286	protein	1264:1270	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	11	81	theme	O-GlcNAc	2018:2025	arg1	modification					2046:2057	the O-GlcNAc post-translational modification	2014:2057	the O-GlcNAc post-translational modification of nuclear and cytosolic proteins	2014:2091	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	8	82	theme	repressor	1353:1361	arg1	mSin3A-HDAC1					1371:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1318:1382	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	5	83	theme	L254F-OGT	901:909	arg1	expression					887:896	Recombinant expression	875:896	Recombinant expression of L254F-OGT	875:909	Recombinant expression of L254F-OGT demonstrated that the enzyme is active as both a glycosyltransferase and an HCF-1 protease.
28302723	6	84	from	reduction	1015:1023	arg1	levels					1032:1037	OGT levels	1028:1037	OGT levels seen in the L254F-OGT individual cells	1028:1076	Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered.
28302723	8	85	theme	mSin3A-HDAC1	1371:1382	arg1	enrichment					1304:1313	an enrichment	1301:1313	an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1	1301:1382	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	7	86	theme	marked	1228:1233	arg1	decrease					1235:1242	a marked decrease	1226:1242	a marked decrease in steady-state OGA protein and mRNA levels	1226:1286	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	4	87	theme	protein	734:740	arg1	levels					742:747	steady-state OGT protein levels	717:747	steady-state OGT protein levels	717:747	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	8	88	theme	promoter	1400:1407	arg1	region					1409:1414	the proximal promoter region	1387:1414	the proximal promoter region of OGA	1387:1421	We observed an enrichment of the OGT-containing transcriptional repressor complex mSin3A-HDAC1 at the proximal promoter region of OGA and correspondingly decreased OGA promoter activity in affected cells.
28302723	10	89	theme	p.L254F	1717:1723	arg1	mutation					1726:1733	the 759G>T (p.L254F) mutation	1705:1733	the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism	1705:1780	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	7	90	theme	affected	1195:1202	arg1	individuals					1204:1214	affected individuals	1195:1214	affected individuals	1195:1214	Surprisingly, lymphoblastoids from affected individuals displayed a marked decrease in steady-state OGA protein and mRNA levels.
28302723	11	91	theme	regulatory	1934:1943	arg1	OGT					1993:1995	OGT	1993:1995	OGT	1993:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	91	theme	regulatory	1934:1943	arg1	domain					1982:1987	the tetratricopeptide repeat domain	1953:1987	the tetratricopeptide repeat domain	1953:1987	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	91	theme	regulatory	1934:1943	arg1	domain					1945:1950	the regulatory domain	1930:1950	the regulatory domain (the tetratricopeptide repeat domain) of OGT	1930:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	10	92	theme	759G>T	1709:1714	arg1	mutation					1726:1733	the 759G>T (p.L254F) mutation	1705:1733	the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism	1705:1780	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	4	93	from	decrease	705:712	arg1	levels					742:747	steady-state OGT protein levels	717:747	steady-state OGT protein levels	717:747	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	6	94	theme	L254F-OGT	1051:1059	arg1	cells					1072:1076	the L254F-OGT individual cells	1047:1076	the L254F-OGT individual cells	1047:1076	Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered.
28302723	4	95	theme	steady-state	717:728	arg1	levels					742:747	steady-state OGT protein levels	717:747	steady-state OGT protein levels	717:747	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	3	96	theme	X-chromosome	474:485	arg1	screen					493:498	An X-chromosome exome screen	471:498	An X-chromosome exome screen	471:498	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	0	97	theme	missense	41:48	arg1	mutation					50:57	a missense mutation	39:57	a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability	39:177	Identification and characterization of a missense mutation in the O-linked β-N-acetylglucosamine (O-GlcNAc) transferase gene that segregates with X-linked intellectual disability.
28302723	10	98	theme	mutation	1726:1733	arg1	consequences					1689:1700	the molecular consequences	1675:1700	the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism	1675:1780	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	4	99	theme	affected	805:812	arg1	individuals					814:824	affected individuals	805:824	affected individuals	805:824	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
28302723	10	100	theme	compensation	1759:1770	arg1	mechanism					1772:1780	a compensation mechanism	1757:1780	a compensation mechanism	1757:1780	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	3	101	theme	X-linked	640:647	arg1	XLID					674:677	XLID	674:677	XLID	674:677	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	3	101	theme	X-linked	640:647	arg1	disability					662:671	X-linked intellectual disability	640:671	X-linked intellectual disability (XLID) in an affected family	640:700	An X-chromosome exome screen identified a missense mutation, which encodes an amino acid in the tetratricopeptide repeat, in OGT (759G>T (p.L254F)) that segregates with X-linked intellectual disability (XLID) in an affected family.
28302723	11	102	theme	amino	1903:1907	arg1	substitution					1914:1925	a single amino acid substitution	1894:1925	a single amino acid substitution	1894:1925	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	10	103	from	mutation	1726:1733	arg1	OGT					1738:1740	OGT	1738:1740	OGT	1738:1740	Thus, we have begun to unravel the molecular consequences of the 759G>T (p.L254F) mutation in OGT that uncovered a compensation mechanism, albeit imperfect, given the phenotype of affected individuals, to maintain steady-state O-GlcNAc levels.
28302723	6	104	theme	global	1109:1114	arg1	levels					1125:1130	steady-state global O-GlcNAc levels	1096:1130	steady-state global O-GlcNAc levels	1096:1130	Despite the reduction in OGT levels seen in the L254F-OGT individual cells, we observed that steady-state global O-GlcNAc levels remained grossly unaltered.
28302723	11	105	theme	repeat	1975:1980	arg1	OGT					1993:1995	OGT	1993:1995	OGT	1993:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	105	theme	repeat	1975:1980	arg1	domain					1982:1987	the tetratricopeptide repeat domain	1953:1987	the tetratricopeptide repeat domain	1953:1987	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	11	105	theme	repeat	1975:1980	arg1	domain					1945:1950	the regulatory domain	1930:1950	the regulatory domain (the tetratricopeptide repeat domain) of OGT	1930:1995	Thus, a single amino acid substitution in the regulatory domain (the tetratricopeptide repeat domain) of OGT, which catalyzes the O-GlcNAc post-translational modification of nuclear and cytosolic proteins, appears causal for XLID.
28302723	4	106	theme	lymphoblastoid	774:787	arg1	lines					794:798	isolated lymphoblastoid cell lines	765:798	isolated lymphoblastoid cell lines from affected individuals	765:824	A decrease in steady-state OGT protein levels was observed in isolated lymphoblastoid cell lines from affected individuals, consistent with molecular modeling experiments.
31501520	4	0	from	response	563:570	arg1	O-GlcNAcylated					545:558	O-GlcNAcylated	545:558	O-GlcNAcylated	545:558	PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability.
31501520	5	1	theme	PKM2	739:742	arg1	O-GlcNAcylation					720:734	O-GlcNAcylation	720:734	O-GlcNAcylation of PKM2	720:742	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	7	2	theme	PKM2	960:963	arg1	O-GlcNAcylation					965:979	PKM2 O-GlcNAcylation	960:979	PKM2 O-GlcNAcylation	960:979	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	7	2	theme	PKM2	960:963	arg1	rheostat					996:1003	a metabolic rheostat	984:1003	a metabolic rheostat that mediates exquisite control of aerobic glycolysis	984:1057	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	1	3	theme	tumor	133:137	arg1	growth					139:144	tumor growth	133:144	tumor growth	133:144	Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined.
31501520	5	4	theme	high	614:617	arg1	conditions					627:636	high glucose conditions	614:636	high glucose conditions	614:636	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	3	5	theme	tumor	471:475	arg1	growth					477:482	tumor growth	471:482	tumor growth	471:482	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	4	6	from	O-GlcNAcylated	545:558	arg1	response					563:570	response	563:570	response to changes in glucose availability	563:605	PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability.
31501520	5	7	theme	glucose	619:625	arg1	conditions					627:636	high glucose conditions	614:636	high glucose conditions	614:636	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	3	8	theme	kinase	507:512	arg1	PKM2					518:521	PKM2	518:521	PKM2	518:521	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	3	8	theme	kinase	507:512	arg1	M2					514:515	pyruvate kinase M2	498:515	pyruvate kinase M2 (PKM2)	498:522	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	2	9	theme	lysine	327:332	arg1	activities					352:361	O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities	263:361	activities	352:361	O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities.
31501520	3	10	theme	aerobic	448:454	arg1	glycolysis					456:465	aerobic glycolysis	448:465	aerobic glycolysis	448:465	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	7	11	theme	tumor	931:935	arg1	progression					937:947	tumor progression	931:947	tumor progression	931:947	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	1	12	theme	Cancer	65:70	arg1	cells					72:76	Cancer cells	65:76	Cancer cells	65:76	Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined.
31501520	6	13	theme	tumor	868:872	arg1	growth					874:879	tumor growth	868:879	tumor growth	868:879	O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth.
31501520	3	14	theme	pyruvate	498:505	arg1	PKM2					518:521	PKM2	518:521	PKM2	518:521	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	3	14	theme	pyruvate	498:505	arg1	M2					514:515	pyruvate kinase M2	498:515	pyruvate kinase M2 (PKM2)	498:522	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	3	15	theme	wide	409:412	arg1	range					414:418	a wide range	407:418	a wide range of human cancers	407:435	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	7	16	theme	aerobic	1040:1046	arg1	glycolysis					1048:1057	aerobic glycolysis	1040:1057	aerobic glycolysis	1040:1057	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	7	17	theme	causative	905:913	arg1	role					915:918	a causative role	903:918	a causative role for OGA in tumor progression	903:947	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	2	18	theme	β-N-acetylglucosamine	272:292	arg1	hydrolase					305:313	O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities	263:361	hydrolase	305:313	O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities.
31501520	1	19	theme	molecular	155:163	arg1	basis					165:169	the molecular basis	151:169	the molecular basis of this metabolic shift	151:193	Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined.
31501520	0	20	theme	kinase	29:34	arg1	M2					36:37	pyruvate kinase M2	20:37	pyruvate kinase M2	20:37	O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth.
31501520	2	21	theme	O-linked	263:270	arg1	hydrolase					305:313	O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities	263:361	hydrolase	305:313	O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities.
31501520	3	22	theme	human	423:427	arg1	cancers					429:435	human cancers	423:435	human cancers	423:435	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	0	23	theme	pyruvate	20:27	arg1	M2					36:37	pyruvate kinase M2	20:37	pyruvate kinase M2	20:37	O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth.
31501520	2	24	theme	cryptic	319:325	arg1	activities					352:361	O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities	263:361	activities	352:361	O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities.
31501520	3	25	theme	cancers	429:435	arg1	range					414:418	a wide range	407:418	a wide range of human cancers	407:435	Here, we report that OGA is upregulated in a wide range of human cancers and drives aerobic glycolysis and tumor growth by inhibiting pyruvate kinase M2 (PKM2).
31501520	5	26	theme	O-GlcNAc	747:754	arg1	OGT					769:771	OGT	769:771	OGT	769:771	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	5	26	theme	O-GlcNAc	747:754	arg1	transferase					756:766	O-GlcNAc transferase	747:766	O-GlcNAc transferase (OGT)	747:772	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	5	27	theme	OGA-associated	659:672	arg1	activity					692:699	OGA-associated acetyltransferase activity	659:699	OGA-associated acetyltransferase activity	659:699	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	6	28	theme	aerobic	845:851	arg1	glycolysis					853:862	aerobic glycolysis	845:862	aerobic glycolysis	845:862	O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth.
31501520	2	29	link	O-linked	263:270	arg1	hydrolase					305:313	O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities	263:361	hydrolase	305:313	O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities.
31501520	5	30	theme	acetyltransferase	674:690	arg1	activity					692:699	OGA-associated acetyltransferase activity	659:699	OGA-associated acetyltransferase activity	659:699	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	1	31	theme	metabolic	179:187	arg1	shift					189:193	this metabolic shift	174:193	this metabolic shift	174:193	Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined.
31501520	0	32	theme	tumor	51:55	arg1	growth					57:62	tumor growth	51:62	tumor growth	51:62	O-GlcNAcase targets pyruvate kinase M2 to regulate tumor growth.
31501520	5	33	theme	activity	692:699	arg1	PKM2					639:642	PKM2	639:642	PKM2	639:642	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	5	33	theme	activity	692:699	arg1	target					649:654	a target	647:654	a target	647:654	Under high glucose conditions, PKM2 is a target of OGA-associated acetyltransferase activity, which facilitates O-GlcNAcylation of PKM2 by O-GlcNAc transferase (OGT).
31501520	1	34	theme	aerobic	97:103	arg1	glycolysis					105:114	aerobic glycolysis in order to fuel tumor growth	97:144	aerobic glycolysis in order to fuel tumor growth	97:144	Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined.
31501520	7	35	theme	glycolysis	1048:1057	arg1	control					1029:1035	exquisite control	1019:1035	exquisite control of aerobic glycolysis	1019:1057	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	7	36	from	role	915:918	arg1	progression					937:947	tumor progression	931:947	tumor progression	931:947	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	7	37	theme	metabolic	986:994	arg1	O-GlcNAcylation					965:979	PKM2 O-GlcNAcylation	960:979	PKM2 O-GlcNAcylation	960:979	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	7	37	theme	metabolic	986:994	arg1	rheostat					996:1003	a metabolic rheostat	984:1003	a metabolic rheostat that mediates exquisite control of aerobic glycolysis	984:1057	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	1	38	theme	shift	189:193	arg1	basis					165:169	the molecular basis	151:169	the molecular basis of this metabolic shift	151:193	Cancer cells are known to adopt aerobic glycolysis in order to fuel tumor growth, but the molecular basis of this metabolic shift remains largely undefined.
31501520	7	39	theme	exquisite	1019:1027	arg1	control					1029:1035	exquisite control	1019:1035	exquisite control of aerobic glycolysis	1019:1057	These studies define a causative role for OGA in tumor progression and reveal PKM2 O-GlcNAcylation as a metabolic rheostat that mediates exquisite control of aerobic glycolysis.
31501520	6	40	theme	catalytic	805:813	arg1	activity					815:822	PKM2 catalytic activity	800:822	PKM2 catalytic activity	800:822	O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth.
31501520	2	41	theme	O-GlcNAc	295:302	arg1	hydrolase					305:313	O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities	263:361	hydrolase	305:313	O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities.
31501520	4	42	from	changes	575:581	arg1	availability					594:605	glucose availability	586:605	glucose availability	586:605	PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability.
31501520	6	43	theme	PKM2	800:803	arg1	activity					815:822	PKM2 catalytic activity	800:822	PKM2 catalytic activity	800:822	O-GlcNAcylation inhibits PKM2 catalytic activity and thereby promotes aerobic glycolysis and tumor growth.
31501520	4	44	theme	glucose	586:592	arg1	availability					594:605	glucose availability	586:605	glucose availability	586:605	PKM2 is dynamically O-GlcNAcylated in response to changes in glucose availability.
31501520	2	45	theme	acetyltransferase	334:350	arg1	activities					352:361	O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities	263:361	activities	352:361	O-GlcNAcase (OGA) is an enzyme harboring O-linked β-N-acetylglucosamine (O-GlcNAc) hydrolase and cryptic lysine acetyltransferase activities.
30980499	0	0	theme	matrix	105:110	arg1	Proteomics					0:9	Proteomics	0:9	Proteomics	0:9	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	0	0	theme	matrix	105:110	arg1	analysis					33:40	N-glycoproteomics analysis	15:40	N-glycoproteomics analysis	15:40	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	6	1	theme	bioinformatics	752:765	arg1	analysis					767:774	bioinformatics analysis	752:774	bioinformatics analysis	752:774	The total human TDM proteome was compared with the previously published human dentin proteome, and bioinformatics analysis were performed accordingly.
30980499	1	2	theme	mammalian	174:182	arg1	tissues					184:190	mammalian tissues	174:190	mammalian tissues	174:190	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	6	3	theme	human	663:667	arg1	proteome					673:680	The total human TDM proteome	653:680	The total human TDM proteome	653:680	The total human TDM proteome was compared with the previously published human dentin proteome, and bioinformatics analysis were performed accordingly.
30980499	0	4	theme	dentin	98:103	arg1	matrix					105:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	4	5	theme	human	532:536	arg1	proteome					542:549	human TDM proteome	532:549	human TDM proteome	532:549	Here, we used a shotgun proteomic strategy to profile human TDM proteome.
30980499	9	6	theme	biological	1199:1208	arg1	processes					1210:1218	"biological processes	1198:1218	"biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion	1198:1376	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	7	theme	Ontology	1226:1233	arg1	process					1258:1264	cellular process	1249:1264	cellular process	1249:1264	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	7	theme	Ontology	1226:1233	arg1	process					1345:1351	immune system process	1331:1351	immune system process	1331:1351	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	7	theme	Ontology	1226:1233	arg1	terms					1235:1239	Gene Ontology terms	1221:1239	Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion	1221:1376	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	7	theme	Ontology	1226:1233	arg1	process					1322:1328	metabolic process	1312:1328	metabolic process	1312:1328	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	7	theme	Ontology	1226:1233	arg1	regulation					1278:1287	biological regulation	1267:1287	biological regulation	1267:1287	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	7	theme	Ontology	1226:1233	arg1	adhesion					1369:1376	biological adhesion	1358:1376	biological adhesion	1358:1376	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	7	theme	Ontology	1226:1233	arg1	response					1290:1297	response	1290:1297	response to stimulus	1290:1309	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	6	8	theme	total	657:661	arg1	proteome					673:680	The total human TDM proteome	653:680	The total human TDM proteome	653:680	The total human TDM proteome was compared with the previously published human dentin proteome, and bioinformatics analysis were performed accordingly.
30980499	10	9	theme	dentin	1449:1454	arg1	proteins					1456:1463	dentin proteins	1449:1463	dentin proteins	1449:1463	Thus, our comprehensive study of the human TDM proteome revealed that dentin proteins are more heterogeneous than previously documented.
30980499	5	10	theme	mass	634:637	arg1	spectrometry					639:650	mass spectrometry	634:650	mass spectrometry	634:650	N-glycoproteins were enriched by lectin affinity chromatography and identified by mass spectrometry.
30980499	8	11	theme	N-linked	1009:1016	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	11	theme	N-linked	1009:1016	arg1	COL1A1					1072:1077	COL1A1	1072:1077	COL1A1	1072:1077	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	11	theme	N-linked	1009:1016	arg1	glycoproteins					1018:1030	small integrin-binding ligand N-linked glycoproteins	979:1030	small integrin-binding ligand N-linked glycoproteins (SIBLINGs)	979:1041	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	11	theme	N-linked	1009:1016	arg1	biglycan					1080:1087	biglycan	1080:1087	biglycan	1080:1087	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	11	theme	N-linked	1009:1016	arg1	SIBLINGs					1033:1040	SIBLINGs	1033:1040	SIBLINGs	1033:1040	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	11	theme	N-linked	1009:1016	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	12	link	N-linked	1009:1016	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	12	link	N-linked	1009:1016	arg1	COL1A1					1072:1077	COL1A1	1072:1077	COL1A1	1072:1077	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	12	link	N-linked	1009:1016	arg1	glycoproteins					1018:1030	small integrin-binding ligand N-linked glycoproteins	979:1030	small integrin-binding ligand N-linked glycoproteins (SIBLINGs)	979:1041	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	12	link	N-linked	1009:1016	arg1	biglycan					1080:1087	biglycan	1080:1087	biglycan	1080:1087	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	12	link	N-linked	1009:1016	arg1	SIBLINGs					1033:1040	SIBLINGs	1033:1040	SIBLINGs	1033:1040	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	12	link	N-linked	1009:1016	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	11	13	theme	new	1557:1559	arg1	biomaterials					1561:1572	new biomaterials	1557:1572	new biomaterials for tooth root regeneration	1557:1600	Our findings provide clues for designing new biomaterials for tooth root regeneration and understanding dentin formation.
30980499	7	14	theme	which	881:885	arg1	N-glycoproteins					896:910	N-glycoproteins	896:910	N-glycoproteins	896:910	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	9	15	theme	immune	1331:1336	arg1	process					1345:1351	immune system process	1331:1351	immune system process	1331:1351	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	7	16	theme	identified	921:930	arg1	sites					946:950	318 identified glycosylation sites	917:950	318 identified glycosylation sites	917:950	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	3	17	theme	TDM	426:428	arg1	composition					438:448	TDM protein composition	426:448	TDM protein composition	426:448	However, TDM protein composition has not been characterized.
30980499	4	18	theme	proteomic	502:510	arg1	strategy					512:519	a shotgun proteomic strategy	492:519	a shotgun proteomic strategy to profile human TDM proteome	492:549	Here, we used a shotgun proteomic strategy to profile human TDM proteome.
30980499	5	19	theme	affinity	592:599	arg1	chromatography					601:614	lectin affinity chromatography	585:614	lectin affinity chromatography	585:614	N-glycoproteins were enriched by lectin affinity chromatography and identified by mass spectrometry.
30980499	10	20	theme	proteome	1426:1433	arg1	study					1403:1407	our comprehensive study	1385:1407	our comprehensive study of the human TDM proteome	1385:1433	Thus, our comprehensive study of the human TDM proteome revealed that dentin proteins are more heterogeneous than previously documented.
30980499	2	21	theme	treated	359:365	arg1	scaffold					349:356	dentin-based scaffold	336:356	dentin-based scaffold	336:356	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	2	21	theme	treated	359:365	arg1	TDM					382:384	TDM	382:384	TDM	382:384	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	2	21	theme	treated	359:365	arg1	matrix					374:379	treated dentin matrix	359:379	treated dentin matrix (TDM)	359:385	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	6	22	theme	dentin	731:736	arg1	proteome					738:745	the previously published human dentin proteome	700:745	the previously published human dentin proteome	700:745	The total human TDM proteome was compared with the previously published human dentin proteome, and bioinformatics analysis were performed accordingly.
30980499	9	23	theme	metabolic	1312:1320	arg1	process					1322:1328	metabolic process	1312:1328	metabolic process	1312:1328	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	7	24	theme	mass	846:849	arg1	spectrometry					851:862	mass spectrometry	846:862	mass spectrometry	846:862	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	8	25	theme	dentin	1090:1095	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	10	26	theme	TDM	1422:1424	arg1	proteome					1426:1433	the human TDM proteome	1412:1433	the human TDM proteome	1412:1433	Thus, our comprehensive study of the human TDM proteome revealed that dentin proteins are more heterogeneous than previously documented.
30980499	1	27	theme	Extracellular	113:125	arg1	ECM					135:137	ECM	135:137	ECM	135:137	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	1	27	theme	Extracellular	113:125	arg1	matrix					127:132	Extracellular matrix	113:132	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues	113:190	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	6	28	theme	human	725:729	arg1	proteome					738:745	the previously published human dentin proteome	700:745	the previously published human dentin proteome	700:745	The total human TDM proteome was compared with the previously published human dentin proteome, and bioinformatics analysis were performed accordingly.
30980499	2	29	theme	root	398:401	arg1	regeneration					403:414	tooth root regeneration	392:414	tooth root regeneration	392:414	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	11	30	theme	root	1584:1587	arg1	regeneration					1589:1600	tooth root regeneration	1578:1600	tooth root regeneration	1578:1600	Our findings provide clues for designing new biomaterials for tooth root regeneration and understanding dentin formation.
30980499	9	31	theme	Gene	1221:1224	arg1	process					1258:1264	cellular process	1249:1264	cellular process	1249:1264	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	31	theme	Gene	1221:1224	arg1	process					1345:1351	immune system process	1331:1351	immune system process	1331:1351	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	31	theme	Gene	1221:1224	arg1	terms					1235:1239	Gene Ontology terms	1221:1239	Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion	1221:1376	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	31	theme	Gene	1221:1224	arg1	process					1322:1328	metabolic process	1312:1328	metabolic process	1312:1328	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	31	theme	Gene	1221:1224	arg1	regulation					1278:1287	biological regulation	1267:1287	biological regulation	1267:1287	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	31	theme	Gene	1221:1224	arg1	adhesion					1369:1376	biological adhesion	1358:1376	biological adhesion	1358:1376	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	9	31	theme	Gene	1221:1224	arg1	response					1290:1297	response	1290:1297	response to stimulus	1290:1309	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	2	32	theme	scaffold	349:356	arg1	applicability					319:331	the applicability	315:331	the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration	315:414	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	6	33	theme	published	715:723	arg1	proteome					738:745	the previously published human dentin proteome	700:745	the previously published human dentin proteome	700:745	The total human TDM proteome was compared with the previously published human dentin proteome, and bioinformatics analysis were performed accordingly.
30980499	0	34	theme	N-glycoproteomics	15:31	arg1	analysis					33:40	N-glycoproteomics analysis	15:40	N-glycoproteomics analysis	15:40	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	9	35	theme	biological	1358:1367	arg1	adhesion					1369:1376	biological adhesion	1358:1376	biological adhesion	1358:1376	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	11	36	theme	dentin	1620:1625	arg1	formation					1627:1635	dentin formation	1620:1635	dentin formation	1620:1635	Our findings provide clues for designing new biomaterials for tooth root regeneration and understanding dentin formation.
30980499	9	37	theme	cellular	1249:1256	arg1	process					1258:1264	cellular process	1249:1264	cellular process	1249:1264	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	2	38	theme	dentin-based	336:347	arg1	scaffold					349:356	dentin-based scaffold	336:356	dentin-based scaffold	336:356	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	2	38	theme	dentin-based	336:347	arg1	matrix					374:379	treated dentin matrix	359:379	treated dentin matrix (TDM)	359:385	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	1	39	theme	preclinical	223:233	arg1	applications					267:278	preclinical and clinical tissue engineering applications	223:278	preclinical and clinical tissue engineering applications	223:278	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	3	40	theme	protein	430:436	arg1	composition					438:448	TDM protein composition	426:448	TDM protein composition	426:448	However, TDM protein composition has not been characterized.
30980499	8	41	theme	growth	1128:1133	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	7	42	theme	human	867:871	arg1	TDM					873:875	human TDM	867:875	human TDM	867:875	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	11	43	theme	tooth	1578:1582	arg1	regeneration					1589:1600	tooth root regeneration	1578:1600	tooth root regeneration	1578:1600	Our findings provide clues for designing new biomaterials for tooth root regeneration and understanding dentin formation.
30980499	4	44	used	used	487:490	arg2	we					484:485	we	484:485	we	484:485	Here, we used a shotgun proteomic strategy to profile human TDM proteome.
30980499	8	45	theme	transforming	1115:1126	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	1	46	theme	clinical	239:246	arg1	applications					267:278	preclinical and clinical tissue engineering applications	223:278	preclinical and clinical tissue engineering applications	223:278	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	0	47	theme	matrix-based	62:73	arg1	matrix					105:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	4	48	theme	TDM	538:540	arg1	proteome					542:549	human TDM proteome	532:549	human TDM proteome	532:549	Here, we used a shotgun proteomic strategy to profile human TDM proteome.
30980499	7	49	gly	N-glycoproteins	896:910	arg1	N-glycoproteins					896:910	N-glycoproteins	896:910	N-glycoproteins	896:910	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	9	50	theme	system	1338:1343	arg1	process					1345:1351	immune system process	1331:1351	immune system process	1331:1351	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	0	51	theme	extracellular	48:60	arg1	matrix					105:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	5	52	gly	N-glycoproteins	552:566	arg1	N-glycoproteins					552:566	N-glycoproteins	552:566	N-glycoproteins	552:566	N-glycoproteins were enriched by lectin affinity chromatography and identified by mass spectrometry.
30980499	8	53	theme	factor	1135:1140	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	9	54	theme	biological	1267:1276	arg1	regulation					1278:1287	biological regulation	1267:1287	biological regulation	1267:1287	Glycoproteins were enriched in "biological processes" Gene Ontology terms such as cellular process, biological regulation, response to stimulus, metabolic process, immune system process, and biological adhesion.
30980499	8	55	theme	small	979:983	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	55	theme	small	979:983	arg1	COL1A1					1072:1077	COL1A1	1072:1077	COL1A1	1072:1077	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	55	theme	small	979:983	arg1	glycoproteins					1018:1030	small integrin-binding ligand N-linked glycoproteins	979:1030	small integrin-binding ligand N-linked glycoproteins (SIBLINGs)	979:1041	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	55	theme	small	979:983	arg1	biglycan					1080:1087	biglycan	1080:1087	biglycan	1080:1087	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	55	theme	small	979:983	arg1	SIBLINGs					1033:1040	SIBLINGs	1033:1040	SIBLINGs	1033:1040	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	55	theme	small	979:983	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	10	56	theme	human	1416:1420	arg1	proteome					1426:1433	the human TDM proteome	1412:1433	the human TDM proteome	1412:1433	Thus, our comprehensive study of the human TDM proteome revealed that dentin proteins are more heterogeneous than previously documented.
30980499	8	57	theme	growth	1048:1053	arg1	COL1A1					1072:1077	COL1A1	1072:1077	COL1A1	1072:1077	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	57	theme	growth	1048:1053	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	57	theme	growth	1048:1053	arg1	factors					1055:1061	growth factors	1048:1061	growth factors	1048:1061	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	57	theme	growth	1048:1053	arg1	biglycan					1080:1087	biglycan	1080:1087	biglycan	1080:1087	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	57	theme	growth	1048:1053	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	1	58	used	used	215:218	arg2	biomaterials					146:157	Extracellular matrix (ECM)-based biomaterials	113:157	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues	113:190	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	5	59	theme	lectin	585:590	arg1	chromatography					601:614	lectin affinity chromatography	585:614	lectin affinity chromatography	585:614	N-glycoproteins were enriched by lectin affinity chromatography and identified by mass spectrometry.
30980499	1	60	theme	-based	139:144	arg1	biomaterials					146:157	Extracellular matrix (ECM)-based biomaterials	113:157	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues	113:190	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	1	61	theme	matrix	127:132	arg1	biomaterials					146:157	Extracellular matrix (ECM)-based biomaterials	113:157	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues	113:190	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	1	62	theme	tissue	248:253	arg1	applications					267:278	preclinical and clinical tissue engineering applications	223:278	preclinical and clinical tissue engineering applications	223:278	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	8	63	theme	ligand	1002:1007	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	63	theme	ligand	1002:1007	arg1	COL1A1					1072:1077	COL1A1	1072:1077	COL1A1	1072:1077	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	63	theme	ligand	1002:1007	arg1	glycoproteins					1018:1030	small integrin-binding ligand N-linked glycoproteins	979:1030	small integrin-binding ligand N-linked glycoproteins (SIBLINGs)	979:1041	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	63	theme	ligand	1002:1007	arg1	biglycan					1080:1087	biglycan	1080:1087	biglycan	1080:1087	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	63	theme	ligand	1002:1007	arg1	SIBLINGs					1033:1040	SIBLINGs	1033:1040	SIBLINGs	1033:1040	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	63	theme	ligand	1002:1007	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	2	64	theme	dentin	367:372	arg1	scaffold					349:356	dentin-based scaffold	336:356	dentin-based scaffold	336:356	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	2	64	theme	dentin	367:372	arg1	TDM					382:384	TDM	382:384	TDM	382:384	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	2	64	theme	dentin	367:372	arg1	matrix					374:379	treated dentin matrix	359:379	treated dentin matrix (TDM)	359:385	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	7	65	theme	glycosylation	932:944	arg1	sites					946:950	318 identified glycosylation sites	917:950	318 identified glycosylation sites	917:950	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	1	66	theme	engineering	255:265	arg1	applications					267:278	preclinical and clinical tissue engineering applications	223:278	preclinical and clinical tissue engineering applications	223:278	Extracellular matrix (ECM)-based biomaterials developed from mammalian tissues have been successfully used in preclinical and clinical tissue engineering applications.
30980499	0	67	theme	treated	90:96	arg1	matrix					105:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	7	68	gly	glycosylation	932:944	arg2	sites					946:950	318 identified glycosylation sites	917:950	318 identified glycosylation sites	917:950	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	7	68	gly	glycosylation	932:944	arg2	318					917:919	318	917:919	318	917:919	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	8	69	gly	glycoproteins	1018:1030	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	69	gly	glycoproteins	1018:1030	arg1	COL1A1					1072:1077	COL1A1	1072:1077	COL1A1	1072:1077	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	69	gly	glycoproteins	1018:1030	arg1	glycoproteins					1018:1030	small integrin-binding ligand N-linked glycoproteins	979:1030	small integrin-binding ligand N-linked glycoproteins (SIBLINGs)	979:1041	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	69	gly	glycoproteins	1018:1030	arg1	biglycan					1080:1087	biglycan	1080:1087	biglycan	1080:1087	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	69	gly	glycoproteins	1018:1030	arg1	SIBLINGs					1033:1040	SIBLINGs	1033:1040	SIBLINGs	1033:1040	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	69	gly	glycoproteins	1018:1030	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	70	theme	integrin-binding	985:1000	arg1	beta					1142:1145	transforming growth factor beta 1	1115:1147	transforming growth factor beta 1	1115:1147	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	70	theme	integrin-binding	985:1000	arg1	COL1A1					1072:1077	COL1A1	1072:1077	COL1A1	1072:1077	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	70	theme	integrin-binding	985:1000	arg1	glycoproteins					1018:1030	small integrin-binding ligand N-linked glycoproteins	979:1030	small integrin-binding ligand N-linked glycoproteins (SIBLINGs)	979:1041	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	70	theme	integrin-binding	985:1000	arg1	biglycan					1080:1087	biglycan	1080:1087	biglycan	1080:1087	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	70	theme	integrin-binding	985:1000	arg1	SIBLINGs					1033:1040	SIBLINGs	1033:1040	SIBLINGs	1033:1040	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	8	70	theme	integrin-binding	985:1000	arg1	sialoprotein					1097:1108	dentin sialoprotein	1090:1108	dentin sialoprotein	1090:1108	Collagens, proteoglycans, small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and growth factors, such as COL1A1, biglycan, dentin sialoprotein, and transforming growth factor beta 1, were identified.
30980499	2	71	theme	tooth	392:396	arg1	regeneration					403:414	tooth root regeneration	392:414	tooth root regeneration	392:414	We have previously reported about the applicability of dentin-based scaffold, treated dentin matrix (TDM), for tooth root regeneration.
30980499	10	72	theme	comprehensive	1389:1401	arg1	study					1403:1407	our comprehensive study	1385:1407	our comprehensive study of the human TDM proteome	1385:1433	Thus, our comprehensive study of the human TDM proteome revealed that dentin proteins are more heterogeneous than previously documented.
30980499	0	73	theme	scaffold-human	75:88	arg1	matrix					105:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	an extracellular matrix-based scaffold-human treated dentin matrix	45:110	Proteomics and N-glycoproteomics analysis of an extracellular matrix-based scaffold-human treated dentin matrix.
30980499	7	74	with	N-glycoproteins	896:910	arg1	sites					946:950	318 identified glycosylation sites	917:950	318 identified glycosylation sites	917:950	In total, 708 proteins were identified by mass spectrometry in human TDM, of which 208 were N-glycoproteins with 318 identified glycosylation sites.
30980499	6	75	theme	TDM	669:671	arg1	proteome					673:680	The total human TDM proteome	653:680	The total human TDM proteome	653:680	The total human TDM proteome was compared with the previously published human dentin proteome, and bioinformatics analysis were performed accordingly.
30740857	4	0	theme	FVIII	338:342	arg1	internalization					319:333	CLEC4M internalization	312:333	CLEC4M internalization of FVIII	312:342	CLEC4M internalization of FVIII involves clathrin coated pits.
30740857	15	1	theme	endothelial	1954:1964	arg1	cells					1966:1970	sinusoidal endothelial cells	1943:1970	sinusoidal endothelial cells in the presence or absence of VWF	1943:2004	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	13	2	theme	mannose-exposed	1509:1523	arg1	glycans					1534:1540	mannose-exposed N-linked glycans	1509:1540	mannose-exposed N-linked glycans	1509:1540	CLEC4M binding to recombinant FVIII was dependent on mannose-exposed N-linked glycans.
30740857	5	3	theme	factor	427:432	arg1	FVIII					440:444	FVIII	440:444	FVIII	440:444	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	5	3	theme	factor	427:432	arg1	VIII					434:437	factor VIII	427:437	factor VIII (FVIII)	427:445	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	9	4	dep	presence	1045:1052	arg1	the					1041:1043	the	1041:1043	the	1041:1043	Objective The interaction between FVIII and CLEC4M was characterized in the presence or absence of VWF.
30740857	3	5	from	glycans	294:300	arg1	FVIII					305:309	FVIII	305:309	FVIII	305:309	CLEC4M binds to mannose-containing glycans on FVIII.
30740857	15	6	dep	presence	1979:1986	arg1	the					1975:1977	the	1975:1977	the	1975:1977	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	1	7	theme	factor	174:179	arg1	FVIII					181:185	factor FVIII	174:185	factor FVIII	174:185	Essentials CLEC4M is an endocytic receptor for factor FVIII.
30740857	10	8	with	interactions	1087:1098	arg1	CLEC4M					1105:1110	CLEC4M	1105:1110	CLEC4M	1105:1110	Methods FVIII interactions with CLEC4M were evaluated by in vitro cell-based and solid phase binding assays.
30740857	15	9	theme	liver	1775:1779	arg1	transfer					1781:1788	hydrodynamic liver transfer	1762:1788	hydrodynamic liver transfer	1762:1788	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	15	10	dep	In	1719:1720	arg1	vivo					1722:1725	vivo	1722:1725	vivo	1722:1725	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	3	11	theme	mannose-containing	275:292	arg1	glycans					294:300	mannose-containing glycans	275:300	mannose-containing glycans on FVIII	275:309	CLEC4M binds to mannose-containing glycans on FVIII.
30740857	15	12	theme	VWF	2002:2004	arg1	absence					1991:1997	absence	1991:1997	absence	1991:1997	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	15	12	theme	VWF	2002:2004	arg1	presence					1979:1986	presence	1979:1986	presence	1979:1986	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	13	13	theme	recombinant	1474:1484	arg1	FVIII					1486:1490	recombinant FVIII	1474:1490	recombinant FVIII	1474:1490	CLEC4M binding to recombinant FVIII was dependent on mannose-exposed N-linked glycans.
30740857	15	14	from	C	1865:1865	arg1	mice					1877:1880	normal mice	1870:1880	normal mice	1870:1880	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	6	15	theme	FVIII	670:674	arg1	deficiencies					676:687	some quantitative FVIII deficiencies	652:687	some quantitative FVIII deficiencies	652:687	Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies.
30740857	2	16	theme	VWF-dependent	221:233	arg1	manner					251:256	a VWF-dependent and independent manner	219:256	a VWF-dependent and independent manner	219:256	CLEC4M interacts with FVIII in a VWF-dependent and independent manner.
30740857	5	17	theme	FVIII	518:522	arg1	majority					506:513	the majority	502:513	the majority of FVIII	502:522	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	5	17	theme	FVIII	518:522	arg1	likely					527:532	likely	527:532	likely	527:532	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	8	18	theme	liver-expressed	816:830	arg1	receptor					907:914	a clearance receptor	895:914	a clearance receptor for VWF	895:922	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	8	18	theme	liver-expressed	816:830	arg1	CLEC4M					851:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	13	19	link	N-linked	1525:1532	arg1	glycans					1534:1540	mannose-exposed N-linked glycans	1509:1540	mannose-exposed N-linked glycans	1509:1540	CLEC4M binding to recombinant FVIII was dependent on mannose-exposed N-linked glycans.
30740857	12	20	theme	recombinant	1369:1379	arg1	FVIII					1400:1404	recombinant and plasma-derived FVIII	1369:1404	recombinant and plasma-derived FVIII	1369:1404	Results CLEC4M-expressing HEK 293 cells bound and internalized recombinant and plasma-derived FVIII through VWF-dependent and independent mechanisms.
30740857	8	21	theme	lectin	844:849	arg1	receptor					907:914	a clearance receptor	895:914	a clearance receptor for VWF	895:922	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	8	21	theme	lectin	844:849	arg1	CLEC4M					851:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	12	22	theme	plasma-derived	1385:1398	arg1	FVIII					1400:1404	recombinant and plasma-derived FVIII	1369:1404	recombinant and plasma-derived FVIII	1369:1404	Results CLEC4M-expressing HEK 293 cells bound and internalized recombinant and plasma-derived FVIII through VWF-dependent and independent mechanisms.
30740857	15	23	theme	FVIII	1859:1863	arg1	levels					1831:1836	plasma levels	1824:1836	plasma levels of endogenous murine FVIII:C in normal mice	1824:1880	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	2	24	theme	independent	239:249	arg1	manner					251:256	a VWF-dependent and independent manner	219:256	a VWF-dependent and independent manner	219:256	CLEC4M interacts with FVIII in a VWF-dependent and independent manner.
30740857	15	25	theme	endogenous	1841:1850	arg1	FVIII					1859:1863	endogenous murine FVIII	1841:1863	endogenous murine FVIII	1841:1863	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	10	26	theme	Methods	1073:1079	arg1	interactions					1087:1098	Methods FVIII interactions	1073:1098	Methods FVIII interactions with CLEC4M	1073:1110	Methods FVIII interactions with CLEC4M were evaluated by in vitro cell-based and solid phase binding assays.
30740857	6	27	theme	VWF-free	588:595	arg1	FVIII					597:601	VWF-free FVIII	588:601	VWF-free FVIII	588:601	Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies.
30740857	16	28	theme	clearance	2065:2073	arg1	receptor					2075:2082	a novel clearance receptor	2057:2082	a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF	2057:2169	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	16	28	theme	clearance	2065:2073	arg1	CLEC4M					2047:2052	CLEC4M	2047:2052	CLEC4M	2047:2052	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	5	29	theme	von	395:397	arg1	factor					410:415	Background von Willebrand factor	384:415	Background von Willebrand factor (VWF)	384:421	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	5	29	theme	von	395:397	arg1	VWF					418:420	VWF	418:420	VWF	418:420	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	15	30	theme	human	1911:1915	arg1	FVIII					1917:1921	infused recombinant human FVIII	1891:1921	infused recombinant human FVIII	1891:1921	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	4	31	theme	CLEC4M	312:317	arg1	internalization					319:333	CLEC4M internalization	312:333	CLEC4M internalization of FVIII	312:342	CLEC4M internalization of FVIII involves clathrin coated pits.
30740857	8	32	from	influence	938:946	arg1	FVIII					951:955	FVIII	951:955	FVIII	951:955	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	15	33	theme	infused	1891:1897	arg1	FVIII					1917:1921	infused recombinant human FVIII	1891:1921	infused recombinant human FVIII	1891:1921	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	0	34	theme	lectin	16:21	arg1	CLEC4M					42:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
30740857	11	35	theme	sinusoidal	1229:1238	arg1	cells					1252:1256	sinusoidal endothelial cells	1229:1256	sinusoidal endothelial cells	1229:1256	Interactions between FVIII and CLEC4M or liver sinusoidal endothelial cells were evaluated in vivo by immunohistochemistry.
30740857	15	36	theme	normal	1870:1875	arg1	mice					1877:1880	normal mice	1870:1880	normal mice	1870:1880	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	0	37	theme	receptor	33:40	arg1	CLEC4M					42:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
30740857	7	38	theme	FVIII	766:770	arg1	clearance					730:738	the clearance	726:738	the clearance of VWF-bound and VWF-free FVIII	726:770	The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII are incompletely uncharacterized.
30740857	4	39	theme	coated	362:367	arg1	pits					369:372	clathrin coated pits	353:372	clathrin coated pits	353:372	CLEC4M internalization of FVIII involves clathrin coated pits.
30740857	15	40	theme	hydrodynamic	1762:1773	arg1	transfer					1781:1788	hydrodynamic liver transfer	1762:1788	hydrodynamic liver transfer	1762:1788	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	13	41	theme	N-linked	1525:1532	arg1	glycans					1534:1540	mannose-exposed N-linked glycans	1509:1540	mannose-exposed N-linked glycans	1509:1540	CLEC4M binding to recombinant FVIII was dependent on mannose-exposed N-linked glycans.
30740857	10	42	theme	phase	1160:1164	arg1	assays					1174:1179	in vitro cell-based and solid phase binding assays	1130:1179	assays	1174:1179	Methods FVIII interactions with CLEC4M were evaluated by in vitro cell-based and solid phase binding assays.
30740857	16	43	theme	VWF	2167:2169	arg1	absence					2156:2162	absence	2156:2162	absence	2156:2162	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	16	43	theme	VWF	2167:2169	arg1	presence					2144:2151	presence	2144:2151	presence	2144:2151	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	15	44	theme	CLEC4M	1749:1754	arg1	expression					1735:1744	In vivo hepatic expression	1719:1744	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer	1719:1788	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	14	45	theme	clathrin-coated	1587:1601	arg1	mechanism					1617:1625	a clathrin-coated pit-dependent mechanism	1585:1625	a clathrin-coated pit-dependent mechanism	1585:1625	CLEC4M mediated FVIII internalization via a clathrin-coated pit-dependent mechanism, resulting in transport of FVIII from early and late endosomes for catabolism by lysosomes.
30740857	15	46	theme	sinusoidal	1943:1952	arg1	cells					1966:1970	sinusoidal endothelial cells	1943:1970	sinusoidal endothelial cells in the presence or absence of VWF	1943:2004	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	15	47	from	decrease	1812:1819	arg1	levels					1831:1836	plasma levels	1824:1836	plasma levels of endogenous murine FVIII:C in normal mice	1824:1880	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	14	48	theme	FVIII	1559:1563	arg1	internalization					1565:1579	FVIII internalization	1559:1579	FVIII internalization	1559:1579	CLEC4M mediated FVIII internalization via a clathrin-coated pit-dependent mechanism, resulting in transport of FVIII from early and late endosomes for catabolism by lysosomes.
30740857	15	49	dep	associated	1794:1803	arg1	whereas					1883:1889	whereas	1883:1889	whereas	1883:1889	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	7	50	theme	receptor	694:701	arg1	uncharacterized					789:803	uncharacterized	789:803	uncharacterized	789:803	The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII are incompletely uncharacterized.
30740857	7	50	theme	receptor	694:701	arg1	pathways					703:710	The receptor pathways	690:710	The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII	690:770	The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII are incompletely uncharacterized.
30740857	16	51	from	glycans	2120:2126	arg1	FVIII					2131:2135	FVIII	2131:2135	FVIII	2131:2135	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	5	52	theme	non-covalent	476:487	arg1	complex					489:495	a non-covalent complex	474:495	a non-covalent complex	474:495	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	8	53	theme	clearance	897:905	arg1	CLEC4M					851:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	8	53	theme	clearance	897:905	arg1	receptor					907:914	a clearance receptor	895:914	a clearance receptor for VWF	895:922	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	12	54	theme	independent	1432:1442	arg1	mechanisms					1444:1453	VWF-dependent and independent mechanisms	1414:1453	VWF-dependent and independent mechanisms	1414:1453	Results CLEC4M-expressing HEK 293 cells bound and internalized recombinant and plasma-derived FVIII through VWF-dependent and independent mechanisms.
30740857	6	55	theme	FVIII	597:601	arg1	Clearance					575:583	Clearance	575:583	Clearance of VWF-free FVIII	575:601	Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies.
30740857	7	56	theme	VWF-free	757:764	arg1	FVIII					766:770	VWF-bound and VWF-free FVIII	743:770	VWF-bound and VWF-free FVIII	743:770	The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII are incompletely uncharacterized.
30740857	16	57	dep	presence	2144:2151	arg1	the					2140:2142	the	2140:2142	the	2140:2142	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	12	58	theme	VWF-dependent	1414:1426	arg1	mechanisms					1444:1453	VWF-dependent and independent mechanisms	1414:1453	VWF-dependent and independent mechanisms	1414:1453	Results CLEC4M-expressing HEK 293 cells bound and internalized recombinant and plasma-derived FVIII through VWF-dependent and independent mechanisms.
30740857	6	59	theme	pathological	630:641	arg1	basis					643:647	the pathological basis	626:647	the pathological basis of some quantitative FVIII deficiencies	626:687	Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies.
30740857	13	60	theme	CLEC4M	1456:1461	arg1	binding					1463:1469	CLEC4M binding	1456:1469	CLEC4M binding to recombinant FVIII	1456:1490	CLEC4M binding to recombinant FVIII was dependent on mannose-exposed N-linked glycans.
30740857	1	61	theme	Essentials	127:136	arg1	CLEC4M					138:143	Essentials CLEC4M	127:143	Essentials CLEC4M	127:143	Essentials CLEC4M is an endocytic receptor for factor FVIII.
30740857	1	61	theme	Essentials	127:136	arg1	receptor					161:168	an endocytic receptor	148:168	an endocytic receptor for factor FVIII	148:185	Essentials CLEC4M is an endocytic receptor for factor FVIII.
30740857	8	62	theme	human	810:814	arg1	receptor					907:914	a clearance receptor	895:914	a clearance receptor for VWF	895:922	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	8	62	theme	human	810:814	arg1	CLEC4M					851:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	5	63	theme	Willebrand	399:408	arg1	factor					410:415	Background von Willebrand factor	384:415	Background von Willebrand factor (VWF)	384:421	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	5	63	theme	Willebrand	399:408	arg1	VWF					418:420	VWF	418:420	VWF	418:420	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	15	64	theme	murine	1852:1857	arg1	FVIII					1859:1863	endogenous murine FVIII	1841:1863	endogenous murine FVIII	1841:1863	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	0	65	theme	factor	72:77	arg1	VIII					79:82	factor VIII	72:82	factor VIII	72:82	The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
30740857	9	66	theme	VWF	1068:1070	arg1	absence					1057:1063	absence	1057:1063	absence	1057:1063	Objective The interaction between FVIII and CLEC4M was characterized in the presence or absence of VWF.
30740857	9	66	theme	VWF	1068:1070	arg1	presence					1045:1052	presence	1045:1052	presence	1045:1052	Objective The interaction between FVIII and CLEC4M was characterized in the presence or absence of VWF.
30740857	8	67	theme	endothelial	832:842	arg1	receptor					907:914	a clearance receptor	895:914	a clearance receptor for VWF	895:922	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	8	67	theme	endothelial	832:842	arg1	CLEC4M					851:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M	806:856	The human liver-expressed endothelial lectin CLEC4M has been previously characterized as a clearance receptor for VWF, although its influence on FVIII is unknown.
30740857	14	68	theme	late	1675:1678	arg1	endosomes					1680:1688	early and late endosomes	1665:1688	early and late endosomes for catabolism by lysosomes	1665:1716	CLEC4M mediated FVIII internalization via a clathrin-coated pit-dependent mechanism, resulting in transport of FVIII from early and late endosomes for catabolism by lysosomes.
30740857	10	69	theme	FVIII	1081:1085	arg1	interactions					1087:1098	Methods FVIII interactions	1073:1098	Methods FVIII interactions with CLEC4M	1073:1110	Methods FVIII interactions with CLEC4M were evaluated by in vitro cell-based and solid phase binding assays.
30740857	1	70	theme	endocytic	151:159	arg1	CLEC4M					138:143	Essentials CLEC4M	127:143	Essentials CLEC4M	127:143	Essentials CLEC4M is an endocytic receptor for factor FVIII.
30740857	1	70	theme	endocytic	151:159	arg1	receptor					161:168	an endocytic receptor	148:168	an endocytic receptor for factor FVIII	148:185	Essentials CLEC4M is an endocytic receptor for factor FVIII.
30740857	14	71	theme	early	1665:1669	arg1	endosomes					1680:1688	early and late endosomes	1665:1688	early and late endosomes for catabolism by lysosomes	1665:1716	CLEC4M mediated FVIII internalization via a clathrin-coated pit-dependent mechanism, resulting in transport of FVIII from early and late endosomes for catabolism by lysosomes.
30740857	15	72	theme	plasma	1824:1829	arg1	levels					1831:1836	plasma levels	1824:1836	plasma levels of endogenous murine FVIII:C in normal mice	1824:1880	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	0	73	theme	VWF-dependent	89:101	arg1	manner					119:124	a VWF-dependent and independent manner	87:124	a VWF-dependent and independent manner	87:124	The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
30740857	9	74	dep	Objective	969:977	arg1	characterized					1024:1036	characterized	1024:1036	was characterized in the presence or absence of VWF	1020:1070	Objective The interaction between FVIII and CLEC4M was characterized in the presence or absence of VWF.
30740857	5	75	theme	Background	384:393	arg1	factor					410:415	Background von Willebrand factor	384:415	Background von Willebrand factor (VWF)	384:421	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	5	75	theme	Background	384:393	arg1	VWF					418:420	VWF	418:420	VWF	418:420	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	14	76	theme	FVIII	1654:1658	arg1	transport					1641:1649	transport	1641:1649	transport of FVIII	1641:1658	CLEC4M mediated FVIII internalization via a clathrin-coated pit-dependent mechanism, resulting in transport of FVIII from early and late endosomes for catabolism by lysosomes.
30740857	15	77	theme	recombinant	1899:1909	arg1	FVIII					1917:1921	infused recombinant human FVIII	1891:1921	infused recombinant human FVIII	1891:1921	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	0	78	theme	independent	107:117	arg1	manner					119:124	a VWF-dependent and independent manner	87:124	a VWF-dependent and independent manner	87:124	The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
30740857	16	79	dep	Conclusions	2007:2017	arg1	suggest					2034:2040	suggest	2034:2040	suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF	2034:2169	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	6	80	theme	deficiencies	676:687	arg1	basis					643:647	the pathological basis	626:647	the pathological basis of some quantitative FVIII deficiencies	626:687	Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies.
30740857	0	81	theme	endothelial	4:14	arg1	CLEC4M					42:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
30740857	15	82	dep	levels	1831:1836	arg1	C					1865:1865	C	1865:1865	plasma levels of endogenous murine FVIII:C in normal mice	1824:1880	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	16	83	theme	mannose-exposed	2104:2118	arg1	glycans					2120:2126	mannose-exposed glycans	2104:2126	mannose-exposed glycans on FVIII	2104:2135	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	6	84	theme	quantitative	657:668	arg1	deficiencies					676:687	some quantitative FVIII deficiencies	652:687	some quantitative FVIII deficiencies	652:687	Clearance of VWF-free FVIII is rapid and underlies the pathological basis of some quantitative FVIII deficiencies.
30740857	0	85	theme	clearance	23:31	arg1	CLEC4M					42:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M	0:47	The endothelial lectin clearance receptor CLEC4M binds and internalizes factor VIII in a VWF-dependent and independent manner.
30740857	5	86	theme	VWF-dependent	551:563	arg1	pathways					565:572	VWF-dependent pathways	551:572	VWF-dependent pathways	551:572	SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate in the plasma as a non-covalent complex, and the majority of FVIII is likely to be cleared by VWF-dependent pathways.
30740857	12	87	theme	HEK	1332:1334	arg1	cells					1340:1344	HEK 293 cells	1332:1344	HEK 293 cells	1332:1344	Results CLEC4M-expressing HEK 293 cells bound and internalized recombinant and plasma-derived FVIII through VWF-dependent and independent mechanisms.
30740857	12	88	link	plasma-derived	1385:1398	arg1	FVIII					1400:1404	recombinant and plasma-derived FVIII	1369:1404	recombinant and plasma-derived FVIII	1369:1404	Results CLEC4M-expressing HEK 293 cells bound and internalized recombinant and plasma-derived FVIII through VWF-dependent and independent mechanisms.
30740857	11	89	theme	endothelial	1240:1250	arg1	cells					1252:1256	sinusoidal endothelial cells	1229:1256	sinusoidal endothelial cells	1229:1256	Interactions between FVIII and CLEC4M or liver sinusoidal endothelial cells were evaluated in vivo by immunohistochemistry.
30740857	10	90	theme	binding	1166:1172	arg1	assays					1174:1179	in vitro cell-based and solid phase binding assays	1130:1179	assays	1174:1179	Methods FVIII interactions with CLEC4M were evaluated by in vitro cell-based and solid phase binding assays.
30740857	4	91	theme	clathrin	353:360	arg1	pits					369:372	clathrin coated pits	353:372	clathrin coated pits	353:372	CLEC4M internalization of FVIII involves clathrin coated pits.
30740857	10	92	theme	solid	1154:1158	arg1	assays					1174:1179	in vitro cell-based and solid phase binding assays	1130:1179	assays	1174:1179	Methods FVIII interactions with CLEC4M were evaluated by in vitro cell-based and solid phase binding assays.
30740857	14	93	theme	pit-dependent	1603:1615	arg1	mechanism					1617:1625	a clathrin-coated pit-dependent mechanism	1585:1625	a clathrin-coated pit-dependent mechanism	1585:1625	CLEC4M mediated FVIII internalization via a clathrin-coated pit-dependent mechanism, resulting in transport of FVIII from early and late endosomes for catabolism by lysosomes.
30740857	15	94	from	cells	1966:1970	arg1	absence					1991:1997	absence	1991:1997	absence	1991:1997	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	15	94	from	cells	1966:1970	arg1	presence					1979:1986	presence	1979:1986	presence	1979:1986	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	15	95	theme	hepatic	1727:1733	arg1	expression					1735:1744	In vivo hepatic expression	1719:1744	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer	1719:1788	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30740857	11	96	dep	FVIII	1203:1207	arg1	cells					1252:1256	sinusoidal endothelial cells	1229:1256	sinusoidal endothelial cells	1229:1256	Interactions between FVIII and CLEC4M or liver sinusoidal endothelial cells were evaluated in vivo by immunohistochemistry.
30740857	7	97	theme	VWF-bound	743:751	arg1	FVIII					766:770	VWF-bound and VWF-free FVIII	743:770	VWF-bound and VWF-free FVIII	743:770	The receptor pathways that regulate the clearance of VWF-bound and VWF-free FVIII are incompletely uncharacterized.
30740857	16	98	theme	novel	2059:2063	arg1	receptor					2075:2082	a novel clearance receptor	2057:2082	a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF	2057:2169	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	16	98	theme	novel	2059:2063	arg1	CLEC4M					2047:2052	CLEC4M	2047:2052	CLEC4M	2047:2052	Conclusions These findings suggest that CLEC4M is a novel clearance receptor that interacts with mannose-exposed glycans on FVIII in the presence or absence of VWF.
30740857	15	99	theme	In	1719:1720	arg1	expression					1735:1744	In vivo hepatic expression	1719:1744	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer	1719:1788	In vivo hepatic expression of CLEC4M after hydrodynamic liver transfer was associated with a decrease in plasma levels of endogenous murine FVIII:C in normal mice, whereas infused recombinant human FVIII was associated with sinusoidal endothelial cells in the presence or absence of VWF.
30701557	6	0	theme	HEK293	862:867	arg1	cells					869:873	STT3A-/- HEK293 cells	853:873	STT3A-/- HEK293 cells	853:873	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	9	1	theme	multiple	1565:1572	arg1	variants					1590:1597	multiple disease-causing variants	1565:1597	multiple disease-causing variants in STT3A	1565:1606	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	6	2	with	studies	840:846	arg1	cells					869:873	STT3A-/- HEK293 cells	853:873	STT3A-/- HEK293 cells	853:873	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	3	3	theme	reported	638:645	arg1	symptoms					647:654	the previously reported symptoms	623:654	the previously reported symptoms of developmental delay and seizures	623:690	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	2	4	theme	homozygous	322:331	arg1	p.Val626Ala					372:382	p.Val626Ala	372:382	p.Val626Ala	372:382	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	2	4	theme	homozygous	322:331	arg1	c.1877C>T					361:369	a homozygous pathogenic missense variant c.1877C>T	320:369	a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A	320:392	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	8	5	from	level	1333:1337	arg1	patient					1346:1352	our patient	1342:1352	our patient	1342:1352	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	1	6	theme	transferrin	237:247	arg1	pattern					249:255	a type I carbohydrate deficient transferrin pattern	205:255	a type I carbohydrate deficient transferrin pattern	205:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	3	7	theme	seizures	683:690	arg1	symptoms					647:654	the previously reported symptoms	623:654	the previously reported symptoms of developmental delay and seizures	623:690	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	8	theme	low	530:532	arg1	VIII					541:544	chronically low Factor VIII	518:544	chronically low Factor VIII (FVIII)	518:552	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	8	theme	low	530:532	arg1	FVIII					547:551	FVIII	547:551	FVIII	547:551	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	6	9	theme	Functional	829:838	arg1	studies					840:846	Functional studies	829:846	Functional studies with STT3A-/- HEK293 cells	829:873	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	3	10	theme	delay	673:677	arg1	symptoms					647:654	the previously reported symptoms	623:654	the previously reported symptoms of developmental delay and seizures	623:690	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	7	11	theme	acceptors	1057:1065	arg1	glycosylation					1025:1037	decreased glycosylation	1015:1037	decreased glycosylation of STT3A-specific acceptors	1015:1065	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	1	12	theme	developmental	155:167	arg1	delay					169:173	developmental delay	155:173	developmental delay	155:173	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	6	13	theme	activity	917:924	arg1	levels					926:931	severely reduced FVIII antigen and activity levels	882:931	levels	926:931	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	7	14	theme	decreased	1015:1023	arg1	glycosylation					1025:1037	decreased glycosylation	1015:1037	decreased glycosylation of STT3A-specific acceptors	1015:1065	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	3	15	theme	VIII	541:544	arg1	levels					586:591	chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels	518:591	chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels	518:591	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	8	16	theme	impaired	1392:1399	arg1	secretion					1407:1415	severely impaired FVIII secretion	1383:1415	severely impaired FVIII secretion	1383:1415	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	17	theme	certain	1231:1237	arg1	N-glycans					1255:1263	certain STT3A-dependent N-glycans	1231:1263	certain STT3A-dependent N-glycans	1231:1263	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	0	18	theme	vWF	16:18	arg1	deficiency					20:29	vWF deficiency	16:29	vWF deficiency	16:29	Factor VIII and vWF deficiency in STT3A-CDG.
30701557	5	19	theme	FVIII	767:771	arg1	levels					781:786	FVIII antigen levels	767:786	FVIII antigen levels	767:786	FVIII antigen levels were too low to quantify in our patient.
30701557	6	20	theme	reduced	891:897	arg1	antigen					905:911	severely reduced FVIII antigen and activity levels	882:931	antigen	905:911	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	8	21	theme	secretion	1407:1415	arg1	level					1333:1337	the decreased FVIII level	1313:1337	the decreased FVIII level in our patient	1313:1352	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	21	theme	secretion	1407:1415	arg1	effect					1368:1373	a combined effect	1357:1373	a combined effect of both severely impaired FVIII secretion and lower plasma VWF level	1357:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	1	22	theme	recessive	86:94	arg1	STT3A-CDG					45:53	STT3A-CDG	45:53	STT3A-CDG (OMIM# 615596)	45:68	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	1	22	theme	recessive	86:94	arg1	disorder					119:126	an autosomal recessive N-linked glycosylation disorder	73:126	an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern	73:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	8	23	theme	lower	1421:1425	arg1	level					1438:1442	lower plasma VWF level	1421:1442	lower plasma VWF level	1421:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	1	24	theme	glycosylation	105:117	arg1	STT3A-CDG					45:53	STT3A-CDG	45:53	STT3A-CDG (OMIM# 615596)	45:68	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	1	24	theme	glycosylation	105:117	arg1	disorder					119:126	an autosomal recessive N-linked glycosylation disorder	73:126	an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern	73:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	8	25	theme	VWF	1434:1436	arg1	level					1438:1442	lower plasma VWF level	1421:1442	lower plasma VWF level	1421:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	26	theme	efficient	1282:1290	arg1	secretion					1298:1306	efficient FVIII secretion	1282:1306	efficient FVIII secretion	1282:1306	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	7	27	theme	severe	1172:1177	arg1	defect					1179:1184	a severe defect	1170:1184	a severe defect in FVIII secretion	1170:1203	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	7	28	from	defect	1179:1184	arg1	secretion					1195:1203	FVIII secretion	1189:1203	FVIII secretion	1189:1203	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	4	29	from	present	724:730	arg1	form					761:764	a mildly hypoglycosylated form	735:764	a mildly hypoglycosylated form	735:764	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	2	30	theme	reported	273:280	arg1	n = 6					289:293	n = 6	289:293	n = 6	289:293	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	2	30	theme	reported	273:280	arg1	cases					282:286	All previously reported cases	258:286	All previously reported cases (n = 6)	258:294	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	8	31	theme	decreased	1317:1325	arg1	level					1333:1337	the decreased FVIII level	1313:1337	the decreased FVIII level in our patient	1313:1352	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	31	theme	decreased	1317:1325	arg1	effect					1368:1373	a combined effect	1357:1373	a combined effect of both severely impaired FVIII secretion and lower plasma VWF level	1357:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	1	32	theme	#	60:60	arg1	STT3A-CDG					45:53	STT3A-CDG	45:53	STT3A-CDG (OMIM# 615596)	45:68	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	1	32	theme	#	60:60	arg1	615596					62:67	OMIM# 615596	56:67	OMIM# 615596	56:67	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	0	33	from	deficiency	20:29	arg1	STT3A-CDG					34:42	STT3A-CDG	34:42	STT3A-CDG	34:42	Factor VIII and vWF deficiency in STT3A-CDG.
30701557	0	34	theme	Factor	0:5	arg1	VIII					7:10	Factor VIII	0:10	Factor VIII	0:10	Factor VIII and vWF deficiency in STT3A-CDG.
30701557	3	35	theme	homozygous	430:439	arg1	p.Tyr360Ser					487:497	p.Tyr360Ser	487:497	p.Tyr360Ser	487:497	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	35	theme	homozygous	430:439	arg1	c.1079A>C					476:484	a novel homozygous likely pathogenic missense variant c.1079A>C	422:484	a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser)	422:498	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	5	36	theme	antigen	773:779	arg1	levels					781:786	FVIII antigen levels	767:786	FVIII antigen levels	767:786	FVIII antigen levels were too low to quantify in our patient.
30701557	4	37	located	present	724:730	arg2	VWF					693:695	VWF	693:695	VWF in our patient's plasma	693:719	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	4	37	located	present	724:730	arg1	form					761:764	a mildly hypoglycosylated form	735:764	a mildly hypoglycosylated form	735:764	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	6	38	from	levels	926:931	arg1	media					948:952	conditioned media	936:952	conditioned media <10% expected	936:966	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	6	39	theme	normal	973:978	arg1	levels					994:999	normal intracellular levels	973:999	normal intracellular levels	973:999	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	1	40	link	N-linked	96:103	arg1	STT3A-CDG					45:53	STT3A-CDG	45:53	STT3A-CDG (OMIM# 615596)	45:68	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	1	40	link	N-linked	96:103	arg1	disorder					119:126	an autosomal recessive N-linked glycosylation disorder	73:126	an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern	73:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	8	41	theme	combined	1359:1366	arg1	level					1333:1337	the decreased FVIII level	1313:1337	the decreased FVIII level in our patient	1313:1352	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	41	theme	combined	1359:1366	arg1	effect					1368:1373	a combined effect	1357:1373	a combined effect of both severely impaired FVIII secretion and lower plasma VWF level	1357:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	3	42	theme	variant	468:474	arg1	p.Tyr360Ser					487:497	p.Tyr360Ser	487:497	p.Tyr360Ser	487:497	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	42	theme	variant	468:474	arg1	c.1079A>C					476:484	a novel homozygous likely pathogenic missense variant c.1079A>C	422:484	a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser)	422:498	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	4	43	gly	hypoglycosylated	744:759	arg1	form					761:764	a mildly hypoglycosylated form	735:764	a mildly hypoglycosylated form	735:764	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	9	44	theme	CDG	1545:1547	arg1	types					1536:1540	most types	1531:1540	most types of CDG	1531:1547	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	3	45	theme	pathogenic	448:457	arg1	p.Tyr360Ser					487:497	p.Tyr360Ser	487:497	p.Tyr360Ser	487:497	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	45	theme	pathogenic	448:457	arg1	c.1079A>C					476:484	a novel homozygous likely pathogenic missense variant c.1079A>C	422:484	a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser)	422:498	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	4	46	theme	hypoglycosylated	744:759	arg1	form					761:764	a mildly hypoglycosylated form	735:764	a mildly hypoglycosylated form	735:764	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	2	47	theme	variant	353:359	arg1	p.Val626Ala					372:382	p.Val626Ala	372:382	p.Val626Ala	372:382	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	2	47	theme	variant	353:359	arg1	c.1877C>T					361:369	a homozygous pathogenic missense variant c.1877C>T	320:369	a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A	320:392	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	1	48	theme	I	212:212	arg1	pattern					249:255	a type I carbohydrate deficient transferrin pattern	205:255	a type I carbohydrate deficient transferrin pattern	205:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	3	49	theme	developmental	659:671	arg1	delay					673:677	developmental delay	659:677	developmental delay	659:677	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	2	50	theme	pathogenic	333:342	arg1	p.Val626Ala					372:382	p.Val626Ala	372:382	p.Val626Ala	372:382	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	2	50	theme	pathogenic	333:342	arg1	c.1877C>T					361:369	a homozygous pathogenic missense variant c.1877C>T	320:369	a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A	320:392	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	1	51	theme	deficient	227:235	arg1	pattern					249:255	a type I carbohydrate deficient transferrin pattern	205:255	a type I carbohydrate deficient transferrin pattern	205:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	6	52	theme	STT3A-/-	853:860	arg1	cells					869:873	STT3A-/- HEK293 cells	853:873	STT3A-/- HEK293 cells	853:873	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	9	53	theme	disease-causing	1574:1588	arg1	variants					1590:1597	multiple disease-causing variants	1565:1597	multiple disease-causing variants in STT3A	1565:1606	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	9	54	theme	STT3A-CDG	1499:1507	arg1	phenotype					1486:1494	phenotype	1486:1494	phenotype	1486:1494	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	9	54	theme	STT3A-CDG	1499:1507	arg1	genotype					1473:1480	the genotype	1469:1480	the genotype	1469:1480	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	7	55	theme	STT3A-specific	1042:1055	arg1	acceptors					1057:1065	STT3A-specific acceptors	1042:1065	STT3A-specific acceptors	1042:1065	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	7	56	gly	glycosylation	1025:1037	arg1	fibroblasts					1070:1080	fibroblasts	1070:1080	fibroblasts from our patient	1070:1097	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	7	56	gly	glycosylation	1025:1037	arg1	acceptors					1057:1065	STT3A-specific acceptors	1042:1065	STT3A-specific acceptors	1042:1065	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	6	57	from	levels	994:999	arg1	media					948:952	conditioned media	936:952	conditioned media <10% expected	936:966	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	3	58	theme	Factor	534:539	arg1	VIII					541:544	chronically low Factor VIII	518:544	chronically low Factor VIII (FVIII)	518:552	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	58	theme	Factor	534:539	arg1	FVIII					547:551	FVIII	547:551	FVIII	547:551	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	1	59	theme	intellectual	176:187	arg1	disability					189:198	intellectual disability	176:198	intellectual disability	176:198	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	8	60	theme	FVIII	1401:1405	arg1	secretion					1407:1415	severely impaired FVIII secretion	1383:1415	severely impaired FVIII secretion	1383:1415	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	4	61	attach	present	724:730	arg2	VWF					693:695	VWF	693:695	VWF in our patient's plasma	693:719	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	4	61	attach	present	724:730	arg1	form					761:764	a mildly hypoglycosylated form	735:764	a mildly hypoglycosylated form	735:764	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	3	62	theme	von	558:560	arg1	vWF					581:583	vWF	581:583	vWF	581:583	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	62	theme	von	558:560	arg1	Factor					573:578	von Willebrand Factor	558:578	von Willebrand Factor (vWF)	558:584	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	6	63	theme	FVIII	899:903	arg1	antigen					905:911	severely reduced FVIII antigen and activity levels	882:931	antigen	905:911	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	1	64	theme	autosomal	76:84	arg1	STT3A-CDG					45:53	STT3A-CDG	45:53	STT3A-CDG (OMIM# 615596)	45:68	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	1	64	theme	autosomal	76:84	arg1	disorder					119:126	an autosomal recessive N-linked glycosylation disorder	73:126	an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern	73:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	8	65	theme	plasma	1427:1432	arg1	level					1438:1442	lower plasma VWF level	1421:1442	lower plasma VWF level	1421:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	66	theme	STT3A-dependent	1239:1253	arg1	N-glycans					1255:1263	certain STT3A-dependent N-glycans	1231:1263	certain STT3A-dependent N-glycans	1231:1263	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	3	67	with	patient	409:415	arg1	p.Tyr360Ser					487:497	p.Tyr360Ser	487:497	p.Tyr360Ser	487:497	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	67	with	patient	409:415	arg1	c.1079A>C					476:484	a novel homozygous likely pathogenic missense variant c.1079A>C	422:484	a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser)	422:498	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	4	68	from	form	761:764	arg1	present					724:730	present	724:730	present	724:730	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	1	69	theme	N-linked	96:103	arg1	STT3A-CDG					45:53	STT3A-CDG	45:53	STT3A-CDG (OMIM# 615596)	45:68	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	1	69	theme	N-linked	96:103	arg1	disorder					119:126	an autosomal recessive N-linked glycosylation disorder	73:126	an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern	73:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	8	70	theme	level	1438:1442	arg1	level					1333:1337	the decreased FVIII level	1313:1337	the decreased FVIII level in our patient	1313:1352	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	70	theme	level	1438:1442	arg1	effect					1368:1373	a combined effect	1357:1373	a combined effect of both severely impaired FVIII secretion and lower plasma VWF level	1357:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	3	71	theme	Factor	573:578	arg1	levels					586:591	chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels	518:591	chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels	518:591	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	6	72	theme	expected	959:966	arg1	media					948:952	conditioned media	936:952	conditioned media <10% expected	936:966	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	7	73	from	patient	1091:1097	arg1	fibroblasts					1070:1080	fibroblasts	1070:1080	fibroblasts from our patient	1070:1097	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	0	74	from	VIII	7:10	arg1	STT3A-CDG					34:42	STT3A-CDG	34:42	STT3A-CDG	34:42	Factor VIII and vWF deficiency in STT3A-CDG.
30701557	8	75	theme	FVIII	1292:1296	arg1	secretion					1298:1306	efficient FVIII secretion	1282:1306	efficient FVIII secretion	1282:1306	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	6	76	theme	conditioned	936:946	arg1	media					948:952	conditioned media	936:952	conditioned media <10% expected	936:966	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	6	77	dep	expected	959:966	arg1	%					957:957	<10%	954:957	<10%	954:957	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	7	78	theme	STT3A	1144:1148	arg1	deficiency					1150:1159	STT3A deficiency	1144:1159	STT3A deficiency	1144:1159	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	1	79	theme	OMIM	56:59	arg1	STT3A-CDG					45:53	STT3A-CDG	45:53	STT3A-CDG (OMIM# 615596)	45:68	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	1	79	theme	OMIM	56:59	arg1	615596					62:67	OMIM# 615596	56:67	OMIM# 615596	56:67	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	9	80	dep	Our	1445:1447	arg1	report					1449:1454	report	1449:1454	report	1449:1454	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	8	81	theme	FVIII	1327:1331	arg1	level					1333:1337	the decreased FVIII level	1313:1337	the decreased FVIII level in our patient	1313:1352	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	8	81	theme	FVIII	1327:1331	arg1	effect					1368:1373	a combined effect	1357:1373	a combined effect of both severely impaired FVIII secretion and lower plasma VWF level	1357:1442	Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level.
30701557	7	82	theme	mechanistic	1112:1122	arg1	explanation					1124:1134	a mechanistic explanation	1110:1134	a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion	1110:1203	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	4	83	from	VWF	693:695	arg1	plasma					714:719	our patient's plasma	700:719	our patient's plasma	700:719	VWF in our patient's plasma is present in a mildly hypoglycosylated form.
30701557	6	84	from	antigen	905:911	arg1	media					948:952	conditioned media	936:952	conditioned media <10% expected	936:966	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	3	85	theme	likely	441:446	arg1	p.Tyr360Ser					487:497	p.Tyr360Ser	487:497	p.Tyr360Ser	487:497	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	85	theme	likely	441:446	arg1	c.1079A>C					476:484	a novel homozygous likely pathogenic missense variant c.1079A>C	422:484	a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser)	422:498	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	9	86	theme	most	1531:1534	arg1	types					1536:1540	most types	1531:1540	most types of CDG	1531:1547	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	6	87	theme	intracellular	980:992	arg1	levels					994:999	normal intracellular levels	973:999	normal intracellular levels	973:999	Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels.
30701557	3	88	theme	novel	424:428	arg1	p.Tyr360Ser					487:497	p.Tyr360Ser	487:497	p.Tyr360Ser	487:497	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	88	theme	novel	424:428	arg1	c.1079A>C					476:484	a novel homozygous likely pathogenic missense variant c.1079A>C	422:484	a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser)	422:498	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	9	89	from	variants	1590:1597	arg1	STT3A					1602:1606	STT3A	1602:1606	STT3A	1602:1606	Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.
30701557	2	90	from	c.1877C>T	361:369	arg1	STT3A					388:392	STT3A	388:392	STT3A	388:392	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	3	91	theme	Willebrand	562:571	arg1	vWF					581:583	vWF	581:583	vWF	581:583	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	91	theme	Willebrand	562:571	arg1	Factor					573:578	von Willebrand Factor	558:578	von Willebrand Factor (vWF)	558:584	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	92	theme	missense	459:466	arg1	p.Tyr360Ser					487:497	p.Tyr360Ser	487:497	p.Tyr360Ser	487:497	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	3	92	theme	missense	459:466	arg1	c.1079A>C					476:484	a novel homozygous likely pathogenic missense variant c.1079A>C	422:484	a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser)	422:498	We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures.
30701557	1	93	theme	type	207:210	arg1	pattern					249:255	a type I carbohydrate deficient transferrin pattern	205:255	a type I carbohydrate deficient transferrin pattern	205:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
30701557	2	94	theme	missense	344:351	arg1	p.Val626Ala					372:382	p.Val626Ala	372:382	p.Val626Ala	372:382	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	2	94	theme	missense	344:351	arg1	c.1877C>T					361:369	a homozygous pathogenic missense variant c.1877C>T	320:369	a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A	320:392	All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A.
30701557	7	95	theme	FVIII	1189:1193	arg1	secretion					1195:1203	FVIII secretion	1189:1203	FVIII secretion	1189:1203	We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion.
30701557	1	96	theme	carbohydrate	214:225	arg1	pattern					249:255	a type I carbohydrate deficient transferrin pattern	205:255	a type I carbohydrate deficient transferrin pattern	205:255	STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern.
31358982	3	0	attach	present	708:714	arg2	glycans					700:706	N-linked glycans	691:706	N-linked glycans present in glycoproteins of the virion envelope	691:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	3	0	attach	present	708:714	arg1	glycoproteins					719:731	glycoproteins	719:731	glycoproteins of the virion envelope	719:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	3	1	theme	N-linked	691:698	arg1	glycans					700:706	N-linked glycans	691:706	N-linked glycans present in glycoproteins of the virion envelope	691:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	1	2	theme	infection	167:175	arg1	phase					148:152	The early phase	138:152	The early phase of influenza infection	138:175	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	2	3	theme	influenza	455:463	arg1	infection					465:473	influenza infection	455:473	influenza infection through type I interferon-mediated production of the chemokine CCL2	455:541	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	5	4	theme	NK	1011:1012	arg1	cells					1014:1018	NK cells	1011:1018	NK cells	1011:1018	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	0	5	theme	lectin	113:118	arg1	SIGN-R1					129:135	C-type lectin receptor SIGN-R1	106:135	C-type lectin receptor SIGN-R1	106:135	Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
31358982	1	6	theme	immune	340:345	arg1	system					347:352	the immune system	336:352	the immune system	336:352	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	4	7	theme	chemokines	819:828	arg1	production					801:810	the production	797:810	the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea	797:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	4	8	from	cells	919:923	arg1	trachea					941:947	the infected trachea	928:947	the infected trachea	928:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	0	9	theme	C-type	106:111	arg1	SIGN-R1					129:135	C-type lectin receptor SIGN-R1	106:135	C-type lectin receptor SIGN-R1	106:135	Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
31358982	3	10	from	glycoproteins	719:731	arg1	present					708:714	present	708:714	present	708:714	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	1	11	theme	initial	262:268	arg1	events					270:275	the initial events	258:275	the initial events of virus recognition and control of viral dissemination by the immune system	258:352	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	2	12	theme	interferon-mediated	490:508	arg1	production					510:519	type I interferon-mediated production	483:519	type I interferon-mediated production of the chemokine CCL2	483:541	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	5	13	theme	uncontrolled	1044:1055	arg1	proliferation					1063:1075	uncontrolled viral proliferation	1044:1075	uncontrolled viral proliferation	1044:1075	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	4	14	theme	IDCs	771:774	arg1	Activation					757:766	Activation	757:766	Activation of IDCs via SIGN-R1	757:786	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	2	15	theme	inflammatory	376:387	arg1	cells					399:403	inflammatory dendritic cells	376:403	inflammatory dendritic cells (IDCs)	376:410	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	2	15	theme	inflammatory	376:387	arg1	IDCs					406:409	IDCs	406:409	IDCs	406:409	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	0	16	theme	receptor	120:127	arg1	SIGN-R1					129:135	C-type lectin receptor SIGN-R1	106:135	C-type lectin receptor SIGN-R1	106:135	Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
31358982	5	17	theme	viral	1057:1061	arg1	proliferation					1063:1075	uncontrolled viral proliferation	1044:1075	uncontrolled viral proliferation	1044:1075	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	3	18	theme	present	708:714	arg1	glycans					700:706	N-linked glycans	691:706	N-linked glycans present in glycoproteins of the virion envelope	691:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	3	19	theme	virion	740:745	arg1	envelope					747:754	the virion envelope	736:754	the virion envelope	736:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	4	20	theme	cells	919:923	arg1	recruitment					873:883	the recruitment	869:883	the recruitment of protective natural killer (NK) cells in the infected trachea	869:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	1	21	theme	upper	191:195	arg1	tract					209:213	the upper respiratory tract	187:213	the upper respiratory tract	187:213	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	3	22	from	present	708:714	arg1	glycoproteins					719:731	glycoproteins	719:731	glycoproteins of the virion envelope	719:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	3	23	gly	glycoproteins	719:731	arg1	glycoproteins					719:731	glycoproteins	719:731	glycoproteins of the virion envelope	719:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	6	24	theme	immune	1192:1197	arg1	protection					1199:1208	immune protection	1192:1208	immune protection against influenza	1192:1226	In sum, our results provide insight into the orchestration of the early cellular and molecular events involved in immune protection against influenza.
31358982	1	25	theme	respiratory	197:207	arg1	tract					209:213	the upper respiratory tract	187:213	the upper respiratory tract	187:213	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	3	26	theme	envelope	747:754	arg1	glycoproteins					719:731	glycoproteins	719:731	glycoproteins of the virion envelope	719:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	4	27	theme	killer	907:912	arg1	cells					919:923	protective natural killer (NK) cells	888:923	protective natural killer (NK) cells in the infected trachea	888:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	4	28	dep	chemokines	819:828	arg1	CXCL9					836:840	CXCL9	836:840	CXCL9	836:840	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	4	28	dep	chemokines	819:828	arg1	CCL5					830:833	CCL5	830:833	CCL5	830:833	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	4	28	dep	chemokines	819:828	arg1	CXCL10					846:851	CXCL10	846:851	CXCL10	846:851	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	4	28	dep	chemokines	819:828	arg1	chemokines					819:828	the chemokines CCL5, CXCL9 and CXCL10	815:851	the chemokines CCL5, CXCL9 and CXCL10	815:851	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	0	29	theme	influenza	19:27	arg1	infection					29:37	influenza infection	19:37	influenza infection	19:37	Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
31358982	1	30	theme	virus	280:284	arg1	recognition					286:296	virus recognition	280:296	virus recognition	280:296	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	2	31	theme	CCL2	538:541	arg1	production					510:519	type I interferon-mediated production	483:519	type I interferon-mediated production of the chemokine CCL2	483:541	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	6	32	theme	early	1144:1148	arg1	events					1173:1178	the early cellular and molecular events	1140:1178	the early cellular and molecular events involved in immune protection against influenza	1140:1226	In sum, our results provide insight into the orchestration of the early cellular and molecular events involved in immune protection against influenza.
31358982	5	33	dep	SIGN-R1	968:974	arg1	the					953:955	the	953:955	the	953:955	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	5	33	dep	SIGN-R1	968:974	arg1	absence					957:963	absence	957:963	absence	957:963	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	0	34	theme	early	48:52	arg1	recognition					54:64	early recognition	48:64	early recognition by inflammatory dendritic cells	48:96	Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
31358982	1	35	theme	recognition	286:296	arg1	events					270:275	the initial events	258:275	the initial events of virus recognition and control of viral dissemination by the immune system	258:352	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	2	36	theme	chemokine	528:536	arg1	CCL2					538:541	the chemokine CCL2	524:541	the chemokine CCL2	524:541	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	3	37	theme	direct	639:644	arg1	recognition					646:656	direct recognition	639:656	direct recognition of the virus	639:669	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	5	38	theme	SIGN-R1	968:974	arg1	impaired					1023:1030	impaired	1023:1030	impaired	1023:1030	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	3	39	link	N-linked	691:698	arg1	glycans					700:706	N-linked glycans	691:706	N-linked glycans present in glycoproteins of the virion envelope	691:754	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	5	40	dep	recruitment	981:991	arg1	the					977:979	the	977:979	the	977:979	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	2	41	theme	dendritic	389:397	arg1	cells					399:403	inflammatory dendritic cells	376:403	inflammatory dendritic cells (IDCs)	376:410	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	2	41	theme	dendritic	389:397	arg1	IDCs					406:409	IDCs	406:409	IDCs	406:409	Here, we report that inflammatory dendritic cells (IDCs) are recruited to the trachea shortly after influenza infection through type I interferon-mediated production of the chemokine CCL2.
31358982	1	42	theme	control	302:308	arg1	events					270:275	the initial events	258:275	the initial events of virus recognition and control of viral dissemination by the immune system	258:352	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	4	43	theme	infected	932:939	arg1	trachea					941:947	the infected trachea	928:947	the infected trachea	928:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	3	44	theme	recruited	565:573	arg1	IDCs					575:578	recruited IDCs	565:578	recruited IDCs	565:578	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	6	45	theme	molecular	1163:1171	arg1	events					1173:1178	the early cellular and molecular events	1140:1178	the early cellular and molecular events involved in immune protection against influenza	1140:1226	In sum, our results provide insight into the orchestration of the early cellular and molecular events involved in immune protection against influenza.
31358982	1	46	theme	viral	313:317	arg1	dissemination					319:331	viral dissemination	313:331	viral dissemination	313:331	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	4	47	theme	protective	888:897	arg1	killer					907:912	protective natural killer	888:912	protective natural killer (NK) cells in the infected trachea	888:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	4	47	theme	protective	888:897	arg1	NK					915:916	NK	915:916	NK	915:916	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	3	48	theme	virus	665:669	arg1	recognition					646:656	direct recognition	639:656	direct recognition of the virus	639:669	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	3	49	theme	receptor	606:613	arg1	SIGN-R1					615:621	the C-type lectin receptor SIGN-R1	588:621	the C-type lectin receptor SIGN-R1	588:621	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	1	50	theme	early	142:146	arg1	phase					148:152	The early phase	138:152	The early phase of influenza infection	138:175	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	4	51	from	recruitment	873:883	arg1	trachea					941:947	the infected trachea	928:947	the infected trachea	928:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	6	52	theme	cellular	1150:1157	arg1	events					1173:1178	the early cellular and molecular events	1140:1178	the early cellular and molecular events involved in immune protection against influenza	1140:1226	In sum, our results provide insight into the orchestration of the early cellular and molecular events involved in immune protection against influenza.
31358982	4	53	theme	natural	899:905	arg1	killer					907:912	protective natural killer	888:912	protective natural killer (NK) cells in the infected trachea	888:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	4	53	theme	natural	899:905	arg1	NK					915:916	NK	915:916	NK	915:916	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	0	54	theme	dendritic	82:90	arg1	cells					92:96	inflammatory dendritic cells	69:96	inflammatory dendritic cells	69:96	Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
31358982	5	55	theme	cells	1014:1018	arg1	activation					997:1006	activation	997:1006	activation	997:1006	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	5	55	theme	cells	1014:1018	arg1	recruitment					981:991	recruitment	981:991	recruitment	981:991	In the absence of SIGN-R1, the recruitment and activation of NK cells is impaired, leading to uncontrolled viral proliferation.
31358982	3	56	theme	C-type	592:597	arg1	SIGN-R1					615:621	the C-type lectin receptor SIGN-R1	588:621	the C-type lectin receptor SIGN-R1	588:621	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	6	57	theme	events	1173:1178	arg1	orchestration					1123:1135	the orchestration	1119:1135	the orchestration of the early cellular and molecular events involved in immune protection against influenza	1119:1226	In sum, our results provide insight into the orchestration of the early cellular and molecular events involved in immune protection against influenza.
31358982	4	58	from	trachea	941:947	arg1	recruitment					873:883	the recruitment	869:883	the recruitment of protective natural killer (NK) cells in the infected trachea	869:947	Activation of IDCs via SIGN-R1 triggers the production of the chemokines CCL5, CXCL9 and CXCL10, which initiate the recruitment of protective natural killer (NK) cells in the infected trachea.
31358982	0	59	theme	inflammatory	69:80	arg1	cells					92:96	inflammatory dendritic cells	69:96	inflammatory dendritic cells	69:96	Protection against influenza infection requires early recognition by inflammatory dendritic cells through C-type lectin receptor SIGN-R1.
31358982	1	60	theme	dissemination	319:331	arg1	control					302:308	control	302:308	control	302:308	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	1	60	theme	dissemination	319:331	arg1	recognition					286:296	virus recognition	280:296	virus recognition	280:296	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
31358982	3	61	theme	lectin	599:604	arg1	SIGN-R1					615:621	the C-type lectin receptor SIGN-R1	588:621	the C-type lectin receptor SIGN-R1	588:621	We further show that recruited IDCs express the C-type lectin receptor SIGN-R1, which mediates direct recognition of the virus by interacting with N-linked glycans present in glycoproteins of the virion envelope.
31358982	1	62	theme	influenza	157:165	arg1	infection					167:175	influenza infection	157:175	influenza infection	157:175	The early phase of influenza infection occurs in the upper respiratory tract and the trachea, but little is known about the initial events of virus recognition and control of viral dissemination by the immune system.
30946947	4	0	theme	ion-exchange	565:576	arg1	combination					550:560	a combination	548:560	a combination of ion-exchange and gel filtration chromatography	548:610	Hyal-Ba was purified by a combination of ion-exchange and gel filtration chromatography.
30946947	14	1	with	Hyal-Ba	1913:1919	arg1	Hyals					1943:1947	other homologous Hyals	1926:1947	other homologous Hyals	1926:1947	The phylogenetic analysis of Hyal-Ba with other homologous Hyals showed the monophyly of viperids.
30946947	3	2	theme	Peruvian	493:500	arg1	atrox					517:521	the Peruvian snake Bothrops atrox	489:521	the Peruvian snake Bothrops atrox	489:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	4	3	theme	gel	582:584	arg1	chromatography					597:610	gel filtration chromatography	582:610	gel filtration chromatography	582:610	Hyal-Ba was purified by a combination of ion-exchange and gel filtration chromatography.
30946947	5	4	theme	monomeric	653:661	arg1	glycoprotein					663:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein	633:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	633:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	5	4	theme	monomeric	653:661	arg1	Hyal-Ba					622:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	13	5	theme	Hyal-Ba	1792:1798	arg1	modeling					1780:1787	Spatial modeling	1772:1787	Spatial modeling of Hyal-Ba	1772:1798	Spatial modeling of Hyal-Ba displayed a TIM-Barrel (α/β) fold and an EGF-like domain in the C-terminal portion.
30946947	6	6	theme	sialic	861:866	arg1	acid					868:871	sialic acid	861:871	sialic acid (0.69%)	861:879	Detected associated carbohydrates were hexoses (16.38%), hexosamines (2.7%) and sialic acid (0.69%).
30946947	6	6	theme	sialic	861:866	arg1	%					878:878	0.69%	874:878	0.69%	874:878	Detected associated carbohydrates were hexoses (16.38%), hexosamines (2.7%) and sialic acid (0.69%).
30946947	12	7	theme	site	1605:1608	arg1	Asp133					1628:1633	Asp133	1628:1633	Asp133	1628:1633	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	7	theme	site	1605:1608	arg1	Trp328					1655:1660	Trp328	1655:1660	Trp328	1655:1660	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	7	theme	site	1605:1608	arg1	residues					1610:1617	the catalytic site residues	1591:1617	the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328)	1591:1661	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	7	theme	site	1605:1608	arg1	Tyr253					1644:1649	Tyr253	1644:1649	Tyr253	1644:1649	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	5	8	theme	69-kDa	635:640	arg1	glycoprotein					663:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein	633:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	633:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	5	8	theme	69-kDa	635:640	arg1	Hyal-Ba					622:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	6	9	theme	associated	790:799	arg1	carbohydrates					801:813	Detected associated carbohydrates	781:813	Detected associated carbohydrates	781:813	Detected associated carbohydrates were hexoses (16.38%), hexosamines (2.7%) and sialic acid (0.69%).
30946947	5	10	theme	acid	701:704	arg1	sequence					706:713	an N-terminal amino acid sequence	681:713	an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	681:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	8	11	dep	pH	1040:1041	arg1	The					1028:1030	The	1028:1030	The	1028:1030	The optimal pH and temperature for maximum activity were 6.0 and 40 °C, respectively, and its Km was 0.31 μM.
30946947	13	12	theme	Spatial	1772:1778	arg1	modeling					1780:1787	Spatial modeling	1772:1787	Spatial modeling of Hyal-Ba	1772:1798	Spatial modeling of Hyal-Ba displayed a TIM-Barrel (α/β) fold and an EGF-like domain in the C-terminal portion.
30946947	7	13	theme	chondroitin	996:1006	arg1	sulfate					1008:1014	chondroitin sulfate	996:1014	chondroitin sulfate	996:1014	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	12	14	theme	catalytic	1595:1603	arg1	Asp133					1628:1633	Asp133	1628:1633	Asp133	1628:1633	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	14	theme	catalytic	1595:1603	arg1	Trp328					1655:1660	Trp328	1655:1660	Trp328	1655:1660	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	14	theme	catalytic	1595:1603	arg1	residues					1610:1617	the catalytic site residues	1591:1617	the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328)	1591:1661	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	14	theme	catalytic	1595:1603	arg1	Tyr253					1644:1649	Tyr253	1644:1649	Tyr253	1644:1649	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	0	15	from	venom	99:103	arg1	characterization					26:41	Biochemical and molecular characterization	0:41	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.	0:104	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	11	16	theme	hemorrhagic	1388:1398	arg1	activity					1414:1421	the hemorrhagic and hemolytic activity	1384:1421	the hemorrhagic and hemolytic activity of whole venom	1384:1436	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	5	17	theme	venom	759:763	arg1	hyaluronidases					765:778	homologous snake venom hyaluronidases	742:778	homologous snake venom hyaluronidases	742:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	7	18	theme	specific	939:946	arg1	U/mg					965:968	specific activity = 437.5 U/mg	939:968	HA; specific activity = 437.5 U/mg	935:968	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	1	19	theme	enzymes	140:146	arg1	source					130:135	a rich source	123:135	a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally	123:290	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	1	19	theme	enzymes	140:146	arg1	venoms					112:117	Snake venoms	106:117	Snake venoms	106:117	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	12	20	theme	amino	1560:1564	arg1	sequence					1529:1536	The Hyal-Ba cDNA sequence	1512:1536	The Hyal-Ba cDNA sequence (2020 bp)	1512:1546	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	20	theme	amino	1560:1564	arg1	motifs					1684:1689	three functional motifs	1667:1689	three functional motifs for N-linked glycosylation	1667:1716	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	20	theme	amino	1560:1564	arg1	residues					1571:1578	449 amino acid residues	1556:1578	449 amino acid residues	1556:1578	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	20	theme	amino	1560:1564	arg1	residues					1610:1617	the catalytic site residues	1591:1617	the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328)	1591:1661	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	10	21	theme	catalytic	1344:1352	arg1	activity					1354:1361	catalytic activity	1344:1361	catalytic activity	1344:1361	Na+ and K+ (0.2 M) positively affect hyaluronidase activity; while Mg2+, Br2+, Ba2+, Cu2+, Zn2+, and Cd2+ reduced catalytic activity.
30946947	5	22	theme	N-terminal	684:693	arg1	sequence					706:713	an N-terminal amino acid sequence	681:713	an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	681:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	11	23	theme	venom	1432:1436	arg1	activity					1414:1421	the hemorrhagic and hemolytic activity	1384:1421	the hemorrhagic and hemolytic activity of whole venom	1384:1436	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	0	24	theme	Peruvian	84:91	arg1	venom					99:103	Bothrops atrox Peruvian snake venom	69:103	Bothrops atrox Peruvian snake venom	69:103	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	15	25	theme	B. atrox	2036:2043	arg1	toxinology					2045:2054	B. atrox toxinology	2036:2054	B. atrox toxinology	2036:2054	Further, Hyal-Ba studies may extend our knowledge of B. atrox toxinology and provides insight to improve the neutralizing strategies of therapeutic antivenoms.
30946947	7	26	dep	HA	935:936	arg1	U/mg					965:968	specific activity = 437.5 U/mg	939:968	HA; specific activity = 437.5 U/mg	935:968	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	5	27	theme	homologous	742:751	arg1	hyaluronidases					765:778	homologous snake venom hyaluronidases	742:778	homologous snake venom hyaluronidases	742:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	7	28	theme	only	913:916	arg1	HA					935:936	HA	935:936	HA; specific activity = 437.5 U/mg	935:968	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	7	28	theme	only	913:916	arg1	acid					929:932	only hyaluronic acid	913:932	only hyaluronic acid (HA; specific activity = 437.5 U/mg)	913:969	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	0	29	theme	atrox	78:82	arg1	venom					99:103	Bothrops atrox Peruvian snake venom	69:103	Bothrops atrox Peruvian snake venom	69:103	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	0	30	theme	Biochemical	0:10	arg1	characterization					26:41	Biochemical and molecular characterization	0:41	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.	0:104	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	12	31	theme	snake	1750:1754	arg1	hyaluronidases					1756:1769	other snake hyaluronidases	1744:1769	other snake hyaluronidases	1744:1769	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	32	theme	cDNA	1524:1527	arg1	sequence					1529:1536	The Hyal-Ba cDNA sequence	1512:1536	The Hyal-Ba cDNA sequence (2020 bp)	1512:1546	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	32	theme	cDNA	1524:1527	arg1	bp					1544:1545	2020 bp	1539:1545	2020 bp	1539:1545	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	32	theme	cDNA	1524:1527	arg1	motifs					1684:1689	three functional motifs	1667:1689	three functional motifs for N-linked glycosylation	1667:1716	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	32	theme	cDNA	1524:1527	arg1	residues					1571:1578	449 amino acid residues	1556:1578	449 amino acid residues	1556:1578	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	32	theme	cDNA	1524:1527	arg1	residues					1610:1617	the catalytic site residues	1591:1617	the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328)	1591:1661	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	14	33	theme	other	1926:1930	arg1	Hyals					1943:1947	other homologous Hyals	1926:1947	other homologous Hyals	1926:1947	The phylogenetic analysis of Hyal-Ba with other homologous Hyals showed the monophyly of viperids.
30946947	0	34	theme	molecular	16:24	arg1	characterization					26:41	Biochemical and molecular characterization	0:41	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.	0:104	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	15	35	theme	therapeutic	2119:2129	arg1	antivenoms					2131:2140	therapeutic antivenoms	2119:2140	therapeutic antivenoms	2119:2140	Further, Hyal-Ba studies may extend our knowledge of B. atrox toxinology and provides insight to improve the neutralizing strategies of therapeutic antivenoms.
30946947	14	36	theme	Hyal-Ba	1913:1919	arg1	analysis					1901:1908	The phylogenetic analysis	1884:1908	The phylogenetic analysis of Hyal-Ba with other homologous Hyals	1884:1947	The phylogenetic analysis of Hyal-Ba with other homologous Hyals showed the monophyly of viperids.
30946947	5	37	dep	69-kDa	635:640	arg1	SDS-PAGE					643:650	SDS-PAGE	643:650	SDS-PAGE	643:650	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	0	38	theme	Bothrops	69:76	arg1	venom					99:103	Bothrops atrox Peruvian snake venom	69:103	Bothrops atrox Peruvian snake venom	69:103	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	10	39	theme	hyaluronidase	1267:1279	arg1	activity					1281:1288	hyaluronidase activity	1267:1288	hyaluronidase activity	1267:1288	Na+ and K+ (0.2 M) positively affect hyaluronidase activity; while Mg2+, Br2+, Ba2+, Cu2+, Zn2+, and Cd2+ reduced catalytic activity.
30946947	0	40	theme	hyaluronidase	50:62	arg1	characterization					26:41	Biochemical and molecular characterization	0:41	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.	0:104	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	8	41	theme	maximum	1063:1069	arg1	activity					1071:1078	maximum activity	1063:1078	maximum activity	1063:1078	The optimal pH and temperature for maximum activity were 6.0 and 40 °C, respectively, and its Km was 0.31 μM.
30946947	12	42	theme	functional	1673:1682	arg1	motifs					1684:1689	three functional motifs	1667:1689	three functional motifs for N-linked glycosylation	1667:1716	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	11	43	theme	acid	1491:1494	arg1	oxidase					1496:1502	an l-amino acid oxidase	1480:1502	an l-amino acid oxidase (LAAO)	1480:1509	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	11	43	theme	acid	1491:1494	arg1	LAAO					1505:1508	LAAO	1505:1508	LAAO	1505:1508	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	12	44	theme	N-linked	1695:1702	arg1	glycosylation					1704:1716	N-linked glycosylation	1695:1716	N-linked glycosylation	1695:1716	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	4	45	theme	filtration	586:595	arg1	chromatography					597:610	gel filtration chromatography	582:610	gel filtration chromatography	582:610	Hyal-Ba was purified by a combination of ion-exchange and gel filtration chromatography.
30946947	3	46	theme	snake	502:506	arg1	atrox					517:521	the Peruvian snake Bothrops atrox	489:521	the Peruvian snake Bothrops atrox	489:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	12	47	link	N-linked	1695:1702	arg1	glycosylation					1704:1716	N-linked glycosylation	1695:1716	N-linked glycosylation	1695:1716	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	3	48	attach	isolated	462:469	arg1	venom					480:484	the venom	476:484	the venom of the Peruvian snake Bothrops atrox	476:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	3	48	attach	isolated	462:469	arg2	Hyal-Ba					453:459	Hyal-Ba	453:459	Hyal-Ba	453:459	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	3	48	attach	isolated	462:469	arg2	hyaluronidase					438:450	a hyaluronidase	436:450	a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox	436:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	11	49	theme	subplantar	1453:1462	arg1	edema					1464:1468	subplantar edema	1453:1468	subplantar edema caused by an l-amino acid oxidase (LAAO)	1453:1509	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	3	50	theme	atrox	517:521	arg1	venom					480:484	the venom	476:484	the venom of the Peruvian snake Bothrops atrox	476:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	1	51	theme	serine	176:181	arg1	proteinases					183:193	serine proteinases phospholipases A2	176:211	serine proteinases phospholipases A2	176:211	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	5	52	theme	amino	695:699	arg1	sequence					706:713	an N-terminal amino acid sequence	681:713	an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	681:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	6	53	theme	Detected	781:788	arg1	carbohydrates					801:813	Detected associated carbohydrates	781:813	Detected associated carbohydrates	781:813	Detected associated carbohydrates were hexoses (16.38%), hexosamines (2.7%) and sialic acid (0.69%).
30946947	1	54	theme	phospholipases	195:208	arg1	A2					210:211	phospholipases A2	195:211	serine proteinases phospholipases A2	176:211	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	11	55	theme	l-amino	1483:1489	arg1	oxidase					1496:1502	an l-amino acid oxidase	1480:1502	an l-amino acid oxidase (LAAO)	1480:1509	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	11	55	theme	l-amino	1483:1489	arg1	LAAO					1505:1508	LAAO	1505:1508	LAAO	1505:1508	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	13	56	theme	TIM-Barrel	1812:1821	arg1	fold					1829:1832	a TIM-Barrel (α/β) fold	1810:1832	a TIM-Barrel (α/β) fold	1810:1832	Spatial modeling of Hyal-Ba displayed a TIM-Barrel (α/β) fold and an EGF-like domain in the C-terminal portion.
30946947	1	57	theme	rich	125:128	arg1	source					130:135	a rich source	123:135	a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally	123:290	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	1	57	theme	rich	125:128	arg1	venoms					112:117	Snake venoms	106:117	Snake venoms	106:117	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	12	58	dep	residues	1610:1617	arg1	Asp133					1628:1633	Asp133	1628:1633	Asp133	1628:1633	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	58	dep	residues	1610:1617	arg1	Trp328					1655:1660	Trp328	1655:1660	Trp328	1655:1660	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	58	dep	residues	1610:1617	arg1	Tyr253					1644:1649	Tyr253	1644:1649	Tyr253	1644:1649	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	58	dep	residues	1610:1617	arg1	residues					1610:1617	the catalytic site residues	1591:1617	the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328)	1591:1661	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	5	59	theme	snake	753:757	arg1	hyaluronidases					765:778	homologous snake venom hyaluronidases	742:778	homologous snake venom hyaluronidases	742:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	15	60	theme	Hyal-Ba	1992:1998	arg1	studies					2000:2006	Hyal-Ba studies	1992:2006	Hyal-Ba studies	1992:2006	Further, Hyal-Ba studies may extend our knowledge of B. atrox toxinology and provides insight to improve the neutralizing strategies of therapeutic antivenoms.
30946947	15	61	theme	toxinology	2045:2054	arg1	knowledge					2023:2031	our knowledge	2019:2031	our knowledge of B. atrox toxinology	2019:2054	Further, Hyal-Ba studies may extend our knowledge of B. atrox toxinology and provides insight to improve the neutralizing strategies of therapeutic antivenoms.
30946947	5	62	gly	glycoprotein	663:674	arg1	glycoprotein					663:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein	633:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	633:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	5	62	gly	glycoprotein	663:674	arg1	Hyal-Ba					622:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	11	63	theme	whole	1426:1430	arg1	venom					1432:1436	whole venom	1426:1436	whole venom	1426:1436	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	0	64	theme	snake	93:97	arg1	venom					99:103	Bothrops atrox Peruvian snake venom	69:103	Bothrops atrox Peruvian snake venom	69:103	Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom.
30946947	7	65	theme	activity = 437.5	948:963	arg1	U/mg					965:968	specific activity = 437.5 U/mg	939:968	HA; specific activity = 437.5 U/mg	935:968	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	14	66	theme	viperids	1973:1980	arg1	monophyly					1960:1968	the monophyly	1956:1968	the monophyly of viperids	1956:1980	The phylogenetic analysis of Hyal-Ba with other homologous Hyals showed the monophyly of viperids.
30946947	5	67	theme	high	723:726	arg1	identity					728:735	high identity	723:735	high identity	723:735	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	12	68	theme	acid	1566:1569	arg1	sequence					1529:1536	The Hyal-Ba cDNA sequence	1512:1536	The Hyal-Ba cDNA sequence (2020 bp)	1512:1546	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	68	theme	acid	1566:1569	arg1	motifs					1684:1689	three functional motifs	1667:1689	three functional motifs for N-linked glycosylation	1667:1716	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	68	theme	acid	1566:1569	arg1	residues					1571:1578	449 amino acid residues	1556:1578	449 amino acid residues	1556:1578	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	68	theme	acid	1566:1569	arg1	residues					1610:1617	the catalytic site residues	1591:1617	the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328)	1591:1661	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	69	theme	other	1744:1748	arg1	hyaluronidases					1756:1769	other snake hyaluronidases	1744:1769	other snake hyaluronidases	1744:1769	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	5	70	theme	Purified	613:620	arg1	Hyal-Ba					622:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba	613:628	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	5	70	theme	Purified	613:620	arg1	glycoprotein					663:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein	633:674	a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	633:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	3	71	theme	hyaluronidase	438:450	arg1	features					424:431	the biochemical and molecular features	394:431	the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox	394:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	8	72	theme	optimal	1032:1038	arg1	pH					1040:1041	optimal pH	1032:1041	optimal pH	1032:1041	The optimal pH and temperature for maximum activity were 6.0 and 40 °C, respectively, and its Km was 0.31 μM.
30946947	7	73	theme	hyaluronic	918:927	arg1	HA					935:936	HA	935:936	HA; specific activity = 437.5 U/mg	935:968	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	7	73	theme	hyaluronic	918:927	arg1	acid					929:932	only hyaluronic acid	913:932	only hyaluronic acid (HA; specific activity = 437.5 U/mg)	913:969	Hyal-Ba selectively hydrolyzed only hyaluronic acid (HA; specific activity = 437.5 U/mg) but it did not hydrolyze chondroitin sulfate or heparin.
30946947	5	74	with	glycoprotein	663:674	arg1	sequence					706:713	an N-terminal amino acid sequence	681:713	an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases	681:778	Purified Hyal-Ba is a 69-kDa (SDS-PAGE) monomeric glycoprotein with an N-terminal amino acid sequence sharing high identity with homologous snake venom hyaluronidases.
30946947	14	75	theme	homologous	1932:1941	arg1	Hyals					1943:1947	other homologous Hyals	1926:1947	other homologous Hyals	1926:1947	The phylogenetic analysis of Hyal-Ba with other homologous Hyals showed the monophyly of viperids.
30946947	1	76	theme	Snake	106:110	arg1	source					130:135	a rich source	123:135	a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally	123:290	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	1	76	theme	Snake	106:110	arg1	venoms					112:117	Snake venoms	106:117	Snake venoms	106:117	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	12	77	theme	Hyal-Ba	1516:1522	arg1	sequence					1529:1536	The Hyal-Ba cDNA sequence	1512:1536	The Hyal-Ba cDNA sequence (2020 bp)	1512:1546	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	77	theme	Hyal-Ba	1516:1522	arg1	bp					1544:1545	2020 bp	1539:1545	2020 bp	1539:1545	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	77	theme	Hyal-Ba	1516:1522	arg1	motifs					1684:1689	three functional motifs	1667:1689	three functional motifs for N-linked glycosylation	1667:1716	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	77	theme	Hyal-Ba	1516:1522	arg1	residues					1571:1578	449 amino acid residues	1556:1578	449 amino acid residues	1556:1578	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	12	77	theme	Hyal-Ba	1516:1522	arg1	residues					1610:1617	the catalytic site residues	1591:1617	the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328)	1591:1661	The Hyal-Ba cDNA sequence (2020 bp) encodes 449 amino acid residues, including the catalytic site residues (Glu135, Asp133, Tyr206, Tyr253 and Trp328) and three functional motifs for N-linked glycosylation, which are conserved with other snake hyaluronidases.
30946947	15	78	theme	antivenoms	2131:2140	arg1	strategies					2105:2114	the neutralizing strategies	2088:2114	the neutralizing strategies of therapeutic antivenoms	2088:2140	Further, Hyal-Ba studies may extend our knowledge of B. atrox toxinology and provides insight to improve the neutralizing strategies of therapeutic antivenoms.
30946947	3	79	theme	molecular	414:422	arg1	features					424:431	the biochemical and molecular features	394:431	the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox	394:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	1	80	dep	proteinases	183:193	arg1	A2					210:211	phospholipases A2	195:211	serine proteinases phospholipases A2	176:211	Snake venoms are a rich source of enzymes such as metalloproteinases, serine proteinases phospholipases A2 and myotoxins, that have been well characterized structurally and functionally.
30946947	11	81	theme	hemolytic	1404:1412	arg1	activity					1414:1421	the hemorrhagic and hemolytic activity	1384:1421	the hemorrhagic and hemolytic activity of whole venom	1384:1436	Hyal-Ba potentiates the hemorrhagic and hemolytic activity of whole venom, but decreased subplantar edema caused by an l-amino acid oxidase (LAAO).
30946947	3	82	theme	biochemical	398:408	arg1	features					424:431	the biochemical and molecular features	394:431	the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox	394:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30946947	14	83	theme	phylogenetic	1888:1899	arg1	analysis					1901:1908	The phylogenetic analysis	1884:1908	The phylogenetic analysis of Hyal-Ba with other homologous Hyals	1884:1947	The phylogenetic analysis of Hyal-Ba with other homologous Hyals showed the monophyly of viperids.
30946947	13	84	theme	C-terminal	1864:1873	arg1	portion					1875:1881	the C-terminal portion	1860:1881	the C-terminal portion	1860:1881	Spatial modeling of Hyal-Ba displayed a TIM-Barrel (α/β) fold and an EGF-like domain in the C-terminal portion.
30946947	15	85	theme	neutralizing	2092:2103	arg1	strategies					2105:2114	the neutralizing strategies	2088:2114	the neutralizing strategies of therapeutic antivenoms	2088:2140	Further, Hyal-Ba studies may extend our knowledge of B. atrox toxinology and provides insight to improve the neutralizing strategies of therapeutic antivenoms.
30946947	4	86	theme	chromatography	597:610	arg1	combination					550:560	a combination	548:560	a combination of ion-exchange and gel filtration chromatography	548:610	Hyal-Ba was purified by a combination of ion-exchange and gel filtration chromatography.
30946947	13	87	theme	EGF-like	1841:1848	arg1	domain					1850:1855	an EGF-like domain	1838:1855	an EGF-like domain	1838:1855	Spatial modeling of Hyal-Ba displayed a TIM-Barrel (α/β) fold and an EGF-like domain in the C-terminal portion.
30946947	3	88	theme	Bothrops	508:515	arg1	atrox					517:521	the Peruvian snake Bothrops atrox	489:521	the Peruvian snake Bothrops atrox	489:521	In this study, we describe the biochemical and molecular features of a hyaluronidase (Hyal-Ba) isolated from the venom of the Peruvian snake Bothrops atrox.
30289687	6	0	theme	high-affinity	1046:1058	arg1	antagonists					1073:1083	high-affinity carbohydrate antagonists	1046:1083	high-affinity carbohydrate antagonists	1046:1083	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	16	1	theme	chair	2912:2916	arg1	conformation					2918:2929	the required 4C1 chair conformation	2895:2929	the required 4C1 chair conformation	2895:2929	These combined techniques pointed to the fact that several α-C-linked mannopyranosides do exist in the required 4C1 chair conformation.
30289687	4	2	theme	carbohydrate-protein	657:676	arg1	interactions					678:689	carbohydrate-protein interactions	657:689	carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells	657:803	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	7	3	theme	mutations	1273:1281	arg1	subject					1252:1258	the subject	1248:1258	the subject of bacterial mutations	1248:1281	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	15	4	theme	conformational	2666:2679	arg1	aspects					2681:2687	conformational aspects	2666:2687	conformational aspects	2666:2687	To decipher this situation, various synthetic approaches, conformational aspects, and restrictions are discussed using molecular modeling, high-field NMR spectroscopy, and X-ray analysis.
30289687	17	5	theme	recent	2944:2949	arg1	findings					2951:2958	recent findings	2944:2958	recent findings in this growing field of interest	2944:2992	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	3	6	from	particular	539:548	arg1	context					448:454	the context	444:454	the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular	444:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	10	7	theme	oligomannoside	1935:1948	arg1	structure					1950:1958	the natural complex oligomannoside structure	1915:1958	the natural complex oligomannoside structure	1915:1958	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	4	8	from	receptors	781:789	arg1	cells					799:803	host cells	794:803	host cells	794:803	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	6	9	theme	bacterial	1001:1009	arg1	adhesion					1011:1018	PapG-mediated bacterial adhesion	987:1018	PapG-mediated bacterial adhesion	987:1018	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	16	10	link	α-C-linked	2855:2864	arg1	mannopyranosides					2866:2881	several α-C-linked mannopyranosides	2847:2881	several α-C-linked mannopyranosides	2847:2881	These combined techniques pointed to the fact that several α-C-linked mannopyranosides do exist in the required 4C1 chair conformation.
30289687	4	11	theme	host	794:797	arg1	cells					799:803	host cells	794:803	host cells	794:803	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	2	12	theme	resistance	356:365	arg1	light					330:334	light	330:334	light of their respective resistance and remaining susceptibility	330:394	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	9	13	theme	binding	1625:1631	arg1	interactions					1638:1649	the intimate binding site interactions	1612:1649	the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1612:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	12	14	theme	multivalent	2178:2188	arg1	architectures					2190:2202	the above multivalent architectures	2168:2202	the above multivalent architectures	2168:2202	In addition, the data were compared to the above multivalent architectures and confirmed the possibility of working with small sugar candidates.
30289687	1	15	theme	microbial	243:251	arg1	resistance					253:262	the increasing microbial resistance	228:262	the increasing microbial resistance	228:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	6	16	theme	therapeutic	1111:1121	arg1	target					1123:1128	a challenging therapeutic target	1097:1128	a challenging therapeutic target of high interest	1097:1145	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	4	17	theme	specific	757:764	arg1	receptors					781:789	specific glycoconjugate receptors	757:789	specific glycoconjugate receptors on host cells	757:803	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	5	18	theme	FimH	837:840	arg1	fimbriae					851:858	the FimH and PapG fimbriae	833:858	the FimH and PapG fimbriae	833:858	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	13	19	theme	FimH	2341:2344	arg1	inhibitors					2346:2355	FimH inhibitors	2341:2355	FimH inhibitors belonging to the family of α-C-linked mannopyranosides	2341:2410	This Account primarily concentrates on the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides.
30289687	5	20	theme	series	935:940	arg1	glycolipids					906:916	glycolipids	906:916	glycolipids	906:916	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	5	20	theme	series	935:940	arg1	glycoproteins					888:900	mannosylated glycoproteins	875:900	mannosylated glycoproteins	875:900	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	11	21	theme	analogues	2015:2023	arg1	series					2005:2010	An appealing and successful series	1977:2010	An appealing and successful series of analogues	1977:2023	An appealing and successful series of analogues have been disclosed, including nanomolecular architectures such as dendrimers, polymers, and liposomes.
30289687	7	22	theme	host	1207:1210	arg1	cells					1212:1216	host cells	1207:1216	host cells	1207:1216	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	16	23	theme	several	2847:2853	arg1	mannopyranosides					2866:2881	several α-C-linked mannopyranosides	2847:2881	several α-C-linked mannopyranosides	2847:2881	These combined techniques pointed to the fact that several α-C-linked mannopyranosides do exist in the required 4C1 chair conformation.
30289687	14	24	theme	E.	2594:2595	arg1	FimH					2602:2605	the E. coli FimH	2590:2605	the E. coli FimH	2590:2605	However, one of the drawbacks associated with C-mannopyranosides has been that they were believed to be in the inverted chair conformation, which is obviously not recognized by the E. coli FimH.
30289687	8	25	theme	FimH	1455:1458	arg1	antagonists					1460:1470	potent FimH antagonists	1448:1470	potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides	1448:1555	To date, there have been several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides.
30289687	9	26	theme	strong	1734:1739	arg1	interactions					1751:1762	the strong necessary interactions	1730:1762	the strong necessary interactions with sugar-possessing hydrophobic aglycones	1730:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	5	27	theme	particular	809:818	arg1	interest					820:827	particular interest	809:827	particular interest	809:827	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	2	28	theme	treatments	303:312	arg1	overview					273:280	A brief overview	265:280	A brief overview of common antibiotic treatments	265:312	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	9	29	theme	so-called	1677:1685	arg1	"					1711:1711	the so-called "tyrosine gate mechanism"	1673:1711	the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1673:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	12	30	theme	sugar	2256:2260	arg1	candidates					2262:2271	small sugar candidates	2250:2271	small sugar candidates	2250:2271	In addition, the data were compared to the above multivalent architectures and confirmed the possibility of working with small sugar candidates.
30289687	14	31	theme	chair	2533:2537	arg1	conformation					2539:2550	the inverted chair conformation	2520:2550	the inverted chair conformation	2520:2550	However, one of the drawbacks associated with C-mannopyranosides has been that they were believed to be in the inverted chair conformation, which is obviously not recognized by the E. coli FimH.
30289687	7	32	theme	processes	1392:1400	arg1	basis					1353:1357	the basis	1349:1357	the basis of the recognition and infection processes	1349:1400	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	2	33	theme	common	285:290	arg1	treatments					303:312	common antibiotic treatments	285:312	common antibiotic treatments	285:312	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	15	34	theme	synthetic	2644:2652	arg1	approaches					2654:2663	various synthetic approaches	2636:2663	various synthetic approaches	2636:2663	To decipher this situation, various synthetic approaches, conformational aspects, and restrictions are discussed using molecular modeling, high-field NMR spectroscopy, and X-ray analysis.
30289687	9	35	theme	tyrosine	1688:1695	arg1	"					1711:1711	the so-called "tyrosine gate mechanism"	1673:1711	the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1673:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	17	36	theme	candidates	3035:3044	arg1	identification					3012:3025	the identification	3008:3025	the identification of drug candidates that have reached clinical phase I	3008:3079	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	5	37	theme	mannosylated	875:886	arg1	glycoproteins					888:900	mannosylated glycoproteins	875:900	mannosylated glycoproteins	875:900	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	3	38	from	infections	477:486	arg1	disease					499:505	Crohn's disease	491:505	Crohn's disease	491:505	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	3	38	from	infections	477:486	arg1	particular					539:548	particular	539:548	particular	539:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	15	39	theme	high-field	2747:2756	arg1	spectroscopy					2762:2773	high-field NMR spectroscopy	2747:2773	high-field NMR spectroscopy	2747:2773	To decipher this situation, various synthetic approaches, conformational aspects, and restrictions are discussed using molecular modeling, high-field NMR spectroscopy, and X-ray analysis.
30289687	1	40	theme	traditional	188:198	arg1	treatments					211:220	traditional antibiotic treatments	188:220	traditional antibiotic treatments given the increasing microbial resistance	188:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	4	41	theme	pathogenic	576:585	arg1	strains					604:610	various pathogenic Escherichia coli strains	568:610	various pathogenic Escherichia coli strains to host cells	568:624	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	5	42	theme	PapG	846:849	arg1	fimbriae					851:858	the FimH and PapG fimbriae	833:858	the FimH and PapG fimbriae	833:858	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	6	43	theme	interest	1138:1145	arg1	target					1123:1128	a challenging therapeutic target	1097:1128	a challenging therapeutic target of high interest	1097:1145	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	17	44	theme	clinical	3064:3071	arg1	I					3079:3079	clinical phase I	3064:3079	clinical phase I	3064:3079	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	5	45	gly	mannosylated	875:886	arg1	glycoproteins					888:900	mannosylated glycoproteins	875:900	mannosylated glycoproteins	875:900	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	1	46	theme	bacterial	110:118	arg1	approach					176:183	a provocative and alternative approach	146:183	a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance	146:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	1	46	theme	bacterial	110:118	arg1	adhesion					120:127	bacterial adhesion	110:127	Preventing bacterial adhesion to host cells	99:141	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	17	47	theme	growing	2968:2974	arg1	field					2976:2980	this growing field	2963:2980	this growing field of interest	2963:2992	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	5	48	theme	galabiose	925:933	arg1	series					935:940	the galabiose series	921:940	the galabiose series	921:940	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	17	49	from	findings	2951:2958	arg1	field					2976:2980	this growing field	2963:2980	this growing field of interest	2963:2992	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	14	50	dep	E.	2594:2595	arg1	coli					2597:2600	coli	2597:2600	coli	2597:2600	However, one of the drawbacks associated with C-mannopyranosides has been that they were believed to be in the inverted chair conformation, which is obviously not recognized by the E. coli FimH.
30289687	8	51	theme	α-d-mannopyranosides	1536:1555	arg1	analogues					1523:1531	unnatural analogues	1513:1531	natural O-linked as well as unnatural analogues of α-d-mannopyranosides	1485:1555	To date, there have been several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides.
30289687	3	52	theme	infections	525:534	arg1	context					448:454	the context	444:454	the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular	444:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	0	53	theme	Mannopyranoside	15:29	arg1	Therapeutics					31:42	Mannopyranoside Therapeutics	15:42	Mannopyranoside Therapeutics	15:42	Development of Mannopyranoside Therapeutics against Adherent-Invasive Escherichia coli Infections.
30289687	6	54	theme	PapG-mediated	987:999	arg1	adhesion					1011:1018	PapG-mediated bacterial adhesion	987:1018	PapG-mediated bacterial adhesion	987:1018	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	9	55	theme	necessary	1741:1749	arg1	interactions					1751:1762	the strong necessary interactions	1730:1762	the strong necessary interactions with sugar-possessing hydrophobic aglycones	1730:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	3	56	theme	infections	477:486	arg1	context					448:454	the context	444:454	the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular	444:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	10	57	theme	monosaccharidic	1852:1866	arg1	d-mannopyranosides					1868:1885	single monosaccharidic d-mannopyranosides	1845:1885	single monosaccharidic d-mannopyranosides	1845:1885	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	3	58	theme	urinary	511:517	arg1	infections					525:534	urinary tract infections	511:534	urinary tract infections in particular	511:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	7	59	theme	carbohydrate	1305:1316	arg1	interactions					1333:1344	the carbohydrate ligand binding interactions	1301:1344	the carbohydrate ligand binding interactions	1301:1344	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	4	60	dep	Escherichia	587:597	arg1	coli					599:602	coli	599:602	coli	599:602	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	0	61	dep	Escherichia	70:80	arg1	coli					82:85	coli	82:85	coli	82:85	Development of Mannopyranoside Therapeutics against Adherent-Invasive Escherichia coli Infections.
30289687	11	62	theme	nanomolecular	2056:2068	arg1	polymers					2104:2111	polymers	2104:2111	polymers	2104:2111	An appealing and successful series of analogues have been disclosed, including nanomolecular architectures such as dendrimers, polymers, and liposomes.
30289687	11	62	theme	nanomolecular	2056:2068	arg1	architectures					2070:2082	nanomolecular architectures	2056:2082	nanomolecular architectures such as dendrimers, polymers, and liposomes	2056:2126	An appealing and successful series of analogues have been disclosed, including nanomolecular architectures such as dendrimers, polymers, and liposomes.
30289687	11	62	theme	nanomolecular	2056:2068	arg1	dendrimers					2092:2101	dendrimers	2092:2101	dendrimers	2092:2101	An appealing and successful series of analogues have been disclosed, including nanomolecular architectures such as dendrimers, polymers, and liposomes.
30289687	11	62	theme	nanomolecular	2056:2068	arg1	liposomes					2118:2126	liposomes	2118:2126	liposomes	2118:2126	An appealing and successful series of analogues have been disclosed, including nanomolecular architectures such as dendrimers, polymers, and liposomes.
30289687	9	63	theme	hydrophobic	1786:1796	arg1	aglycones					1798:1806	sugar-possessing hydrophobic aglycones	1769:1806	sugar-possessing hydrophobic aglycones	1769:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	2	64	theme	susceptibility	381:394	arg1	light					330:334	light	330:334	light of their respective resistance and remaining susceptibility	330:394	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	12	65	theme	small	2250:2254	arg1	candidates					2262:2271	small sugar candidates	2250:2271	small sugar candidates	2250:2271	In addition, the data were compared to the above multivalent architectures and confirmed the possibility of working with small sugar candidates.
30289687	4	66	theme	bacterial	701:709	arg1	organelles					711:720	bacterial organelles	701:720	bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells	701:803	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	10	67	theme	single	1845:1850	arg1	d-mannopyranosides					1868:1885	single monosaccharidic d-mannopyranosides	1845:1885	single monosaccharidic d-mannopyranosides	1845:1885	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	10	68	theme	complex	1927:1933	arg1	structure					1950:1958	the natural complex oligomannoside structure	1915:1958	the natural complex oligomannoside structure	1915:1958	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	13	69	theme	mannopyranosides	2395:2410	arg1	family					2374:2379	the family	2370:2379	the family of α-C-linked mannopyranosides	2370:2410	This Account primarily concentrates on the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides.
30289687	6	70	theme	carbohydrate	1060:1071	arg1	antagonists					1073:1083	high-affinity carbohydrate antagonists	1046:1083	high-affinity carbohydrate antagonists	1046:1083	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	14	71	theme	drawbacks	2433:2441	arg1	one					2422:2424	one	2422:2424	one	2422:2424	However, one of the drawbacks associated with C-mannopyranosides has been that they were believed to be in the inverted chair conformation, which is obviously not recognized by the E. coli FimH.
30289687	14	71	theme	drawbacks	2433:2441	arg1	drawbacks					2433:2441	the drawbacks	2429:2441	the drawbacks associated with C-mannopyranosides	2429:2476	However, one of the drawbacks associated with C-mannopyranosides has been that they were believed to be in the inverted chair conformation, which is obviously not recognized by the E. coli FimH.
30289687	7	72	theme	bacterial	1263:1271	arg1	mutations					1273:1281	bacterial mutations	1263:1281	bacterial mutations	1263:1281	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	15	73	theme	X-ray	2780:2784	arg1	analysis					2786:2793	X-ray analysis	2780:2793	X-ray analysis	2780:2793	To decipher this situation, various synthetic approaches, conformational aspects, and restrictions are discussed using molecular modeling, high-field NMR spectroscopy, and X-ray analysis.
30289687	12	74	theme	working	2237:2243	arg1	possibility					2222:2232	the possibility	2218:2232	the possibility of working with small sugar candidates	2218:2271	In addition, the data were compared to the above multivalent architectures and confirmed the possibility of working with small sugar candidates.
30289687	16	75	theme	4C1	2908:2910	arg1	conformation					2918:2929	the required 4C1 chair conformation	2895:2929	the required 4C1 chair conformation	2895:2929	These combined techniques pointed to the fact that several α-C-linked mannopyranosides do exist in the required 4C1 chair conformation.
30289687	9	76	theme	sugar-possessing	1769:1784	arg1	aglycones					1798:1806	sugar-possessing hydrophobic aglycones	1769:1806	sugar-possessing hydrophobic aglycones	1769:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	10	77	theme	simpler	1963:1969	arg1	ones					1971:1974	simpler ones	1963:1974	simpler ones	1963:1974	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	9	78	theme	thorough	1586:1593	arg1	understanding					1595:1607	a thorough understanding	1584:1607	a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1584:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	6	79	theme	uroepithelial	1023:1035	arg1	cells					1037:1041	uroepithelial cells	1023:1041	uroepithelial cells	1023:1041	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	9	80	with	interactions	1751:1762	arg1	aglycones					1798:1806	sugar-possessing hydrophobic aglycones	1769:1806	sugar-possessing hydrophobic aglycones	1769:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	1	81	theme	antibiotic	200:209	arg1	treatments					211:220	traditional antibiotic treatments	188:220	traditional antibiotic treatments given the increasing microbial resistance	188:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	4	82	theme	glycoconjugate	766:779	arg1	receptors					781:789	specific glycoconjugate receptors	757:789	specific glycoconjugate receptors on host cells	757:803	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	7	83	theme	unlikely	1233:1240	arg1	adhesion					1195:1202	bacterial adhesion	1185:1202	bacterial adhesion to host cells	1185:1216	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	7	83	theme	unlikely	1233:1240	arg1	parameter					1223:1231	a parameter	1221:1231	a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes	1221:1400	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	9	84	theme	intimate	1616:1623	arg1	interactions					1638:1649	the intimate binding site interactions	1612:1649	the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1612:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	6	85	theme	high	1133:1136	arg1	interest					1138:1145	high interest	1133:1145	high interest	1133:1145	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	5	86	theme	interest	820:827	arg1	fimbriae					851:858	the FimH and PapG fimbriae	833:858	the FimH and PapG fimbriae	833:858	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	13	87	link	α-C-linked	2384:2393	arg1	mannopyranosides					2395:2410	α-C-linked mannopyranosides	2384:2410	α-C-linked mannopyranosides	2384:2410	This Account primarily concentrates on the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides.
30289687	2	88	theme	respective	345:354	arg1	resistance					356:365	their respective resistance	339:365	their respective resistance	339:365	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	9	89	theme	site	1633:1636	arg1	interactions					1638:1649	the intimate binding site interactions	1612:1649	the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1612:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	12	90	theme	above	2172:2176	arg1	architectures					2190:2202	the above multivalent architectures	2168:2202	the above multivalent architectures	2168:2202	In addition, the data were compared to the above multivalent architectures and confirmed the possibility of working with small sugar candidates.
30289687	9	91	theme	mechanism	1702:1710	arg1	"					1711:1711	the so-called "tyrosine gate mechanism"	1673:1711	the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1673:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	11	92	theme	successful	1994:2003	arg1	series					2005:2010	An appealing and successful series	1977:2010	An appealing and successful series of analogues	1977:2023	An appealing and successful series of analogues have been disclosed, including nanomolecular architectures such as dendrimers, polymers, and liposomes.
30289687	6	93	theme	challenging	1099:1109	arg1	target					1123:1128	a challenging therapeutic target	1097:1128	a challenging therapeutic target of high interest	1097:1145	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	13	94	theme	inhibitors	2346:2355	arg1	types					2332:2336	the most promising types	2313:2336	the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides	2313:2410	This Account primarily concentrates on the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides.
30289687	2	95	theme	brief	267:271	arg1	overview					273:280	A brief overview	265:280	A brief overview of common antibiotic treatments	265:312	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	10	96	theme	natural	1919:1925	arg1	structure					1950:1958	the natural complex oligomannoside structure	1915:1958	the natural complex oligomannoside structure	1915:1958	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	16	97	theme	α-C-linked	2855:2864	arg1	mannopyranosides					2866:2881	several α-C-linked mannopyranosides	2847:2881	several α-C-linked mannopyranosides	2847:2881	These combined techniques pointed to the fact that several α-C-linked mannopyranosides do exist in the required 4C1 chair conformation.
30289687	7	98	theme	ligand	1318:1323	arg1	interactions					1333:1344	the carbohydrate ligand binding interactions	1301:1344	the carbohydrate ligand binding interactions	1301:1344	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	7	99	theme	bacterial	1185:1193	arg1	adhesion					1195:1202	bacterial adhesion	1185:1202	bacterial adhesion to host cells	1185:1216	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	7	99	theme	bacterial	1185:1193	arg1	parameter					1223:1231	a parameter	1221:1231	a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes	1221:1400	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	7	100	theme	particular	1159:1168	arg1	interest					1170:1177	particular interest	1159:1177	particular interest	1159:1177	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	1	101	theme	provocative	148:158	arg1	approach					176:183	a provocative and alternative approach	146:183	a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance	146:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	1	101	theme	provocative	148:158	arg1	adhesion					120:127	bacterial adhesion	110:127	Preventing bacterial adhesion to host cells	99:141	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	8	102	theme	potent	1448:1453	arg1	antagonists					1460:1470	potent FimH antagonists	1448:1470	potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides	1448:1555	To date, there have been several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides.
30289687	7	103	theme	infection	1382:1390	arg1	processes					1392:1400	the recognition and infection processes	1362:1400	the recognition and infection processes	1362:1400	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	13	104	theme	promising	2322:2330	arg1	types					2332:2336	the most promising types	2313:2336	the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides	2313:2410	This Account primarily concentrates on the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides.
30289687	2	105	theme	antibiotic	292:301	arg1	treatments					303:312	common antibiotic treatments	285:312	common antibiotic treatments	285:312	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	1	106	theme	increasing	232:241	arg1	resistance					253:262	the increasing microbial resistance	228:262	the increasing microbial resistance	228:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	1	107	theme	alternative	164:174	arg1	approach					176:183	a provocative and alternative approach	146:183	a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance	146:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	1	107	theme	alternative	164:174	arg1	adhesion					120:127	bacterial adhesion	110:127	Preventing bacterial adhesion to host cells	99:141	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	17	108	theme	drug	3030:3033	arg1	candidates					3035:3044	drug candidates	3030:3044	drug candidates that have reached clinical phase I	3030:3079	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	4	109	theme	various	568:574	arg1	strains					604:610	various pathogenic Escherichia coli strains	568:610	various pathogenic Escherichia coli strains to host cells	568:624	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	8	110	theme	antagonists	1460:1470	arg1	families					1436:1443	several families	1428:1443	several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides	1428:1555	To date, there have been several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides.
30289687	14	111	theme	inverted	2524:2531	arg1	conformation					2539:2550	the inverted chair conformation	2520:2550	the inverted chair conformation	2520:2550	However, one of the drawbacks associated with C-mannopyranosides has been that they were believed to be in the inverted chair conformation, which is obviously not recognized by the E. coli FimH.
30289687	7	112	theme	recognition	1366:1376	arg1	processes					1392:1400	the recognition and infection processes	1362:1400	the recognition and infection processes	1362:1400	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
30289687	15	113	theme	various	2636:2642	arg1	approaches					2654:2663	various synthetic approaches	2636:2663	various synthetic approaches	2636:2663	To decipher this situation, various synthetic approaches, conformational aspects, and restrictions are discussed using molecular modeling, high-field NMR spectroscopy, and X-ray analysis.
30289687	9	114	theme	gate	1697:1700	arg1	"					1711:1711	the so-called "tyrosine gate mechanism"	1673:1711	the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1673:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	9	115	from	origin	1720:1725	arg1	"					1711:1711	the so-called "tyrosine gate mechanism"	1673:1711	the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1673:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	4	116	theme	Escherichia	587:597	arg1	strains					604:610	various pathogenic Escherichia coli strains	568:610	various pathogenic Escherichia coli strains to host cells	568:624	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	11	117	theme	appealing	1980:1988	arg1	series					2005:2010	An appealing and successful series	1977:2010	An appealing and successful series of analogues	1977:2023	An appealing and successful series of analogues have been disclosed, including nanomolecular architectures such as dendrimers, polymers, and liposomes.
30289687	15	118	theme	NMR	2758:2760	arg1	spectroscopy					2762:2773	high-field NMR spectroscopy	2747:2773	high-field NMR spectroscopy	2747:2773	To decipher this situation, various synthetic approaches, conformational aspects, and restrictions are discussed using molecular modeling, high-field NMR spectroscopy, and X-ray analysis.
30289687	16	119	theme	combined	2802:2809	arg1	techniques					2811:2820	These combined techniques	2796:2820	These combined techniques	2796:2820	These combined techniques pointed to the fact that several α-C-linked mannopyranosides do exist in the required 4C1 chair conformation.
30289687	9	120	theme	interactions	1638:1649	arg1	understanding					1595:1607	a thorough understanding	1584:1607	a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1584:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	1	121	theme	Preventing	99:108	arg1	approach					176:183	a provocative and alternative approach	146:183	a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance	146:262	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	1	121	theme	Preventing	99:108	arg1	adhesion					120:127	bacterial adhesion	110:127	Preventing bacterial adhesion to host cells	99:141	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	17	122	theme	phase	3073:3077	arg1	I					3079:3079	clinical phase I	3064:3079	clinical phase I	3064:3079	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	10	123	theme	aglycones	1832:1840	arg1	modification					1812:1823	modification	1812:1823	modification of the aglycones of single monosaccharidic d-mannopyranosides	1812:1885	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	3	124	from	context	448:454	arg1	disease					499:505	Crohn's disease	491:505	Crohn's disease	491:505	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	3	124	from	context	448:454	arg1	particular					539:548	particular	539:548	particular	539:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	15	125	theme	molecular	2727:2735	arg1	modeling					2737:2744	molecular modeling	2727:2744	molecular modeling	2727:2744	To decipher this situation, various synthetic approaches, conformational aspects, and restrictions are discussed using molecular modeling, high-field NMR spectroscopy, and X-ray analysis.
30289687	8	126	theme	unnatural	1513:1521	arg1	analogues					1523:1531	unnatural analogues	1513:1531	natural O-linked as well as unnatural analogues of α-d-mannopyranosides	1485:1555	To date, there have been several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides.
30289687	0	127	theme	Therapeutics	31:42	arg1	Development					0:10	Development	0:10	Development of Mannopyranoside Therapeutics against Adherent-Invasive Escherichia coli Infections.	0:97	Development of Mannopyranoside Therapeutics against Adherent-Invasive Escherichia coli Infections.
30289687	1	128	theme	host	132:135	arg1	cells					137:141	host cells	132:141	host cells	132:141	Preventing bacterial adhesion to host cells is a provocative and alternative approach to traditional antibiotic treatments given the increasing microbial resistance.
30289687	17	129	theme	interest	2985:2992	arg1	field					2976:2980	this growing field	2963:2980	this growing field of interest	2963:2992	Ultimately, recent findings in this growing field of interest culminated in the identification of drug candidates that have reached clinical phase I.
30289687	10	130	theme	d-mannopyranosides	1868:1885	arg1	aglycones					1832:1840	the aglycones	1828:1840	the aglycones of single monosaccharidic d-mannopyranosides	1828:1885	By modification of the aglycones of single monosaccharidic d-mannopyranosides, it was possible to replace the natural complex oligomannoside structure by simpler ones.
30289687	0	131	theme	Adherent-Invasive	52:68	arg1	Infections					87:96	Adherent-Invasive Escherichia coli Infections	52:96	Adherent-Invasive Escherichia coli Infections	52:96	Development of Mannopyranoside Therapeutics against Adherent-Invasive Escherichia coli Infections.
30289687	8	132	theme	several	1428:1434	arg1	families					1436:1443	several families	1428:1443	several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides	1428:1555	To date, there have been several families of potent FimH antagonists that include natural O-linked as well as unnatural analogues of α-d-mannopyranosides.
30289687	9	133	theme	interactions	1751:1762	arg1	origin					1720:1725	the origin	1716:1725	the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones	1716:1806	These observations led to a thorough understanding of the intimate binding site interactions that helped to reveal the so-called "tyrosine gate mechanism" at the origin of the strong necessary interactions with sugar-possessing hydrophobic aglycones.
30289687	4	134	theme	strains	604:610	arg1	adhesions					555:563	The adhesions	551:563	The adhesions of various pathogenic Escherichia coli strains to host cells	551:624	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	3	135	theme	tract	519:523	arg1	infections					525:534	urinary tract infections	511:534	urinary tract infections in particular	511:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	6	136	theme	blocking	968:975	arg1	FimH-					977:981	blocking FimH-	968:981	blocking FimH-	968:981	Therefore, blocking FimH- and PapG-mediated bacterial adhesion to uroepithelial cells by high-affinity carbohydrate antagonists constitutes a challenging therapeutic target of high interest.
30289687	0	137	dep	Adherent-Invasive	52:68	arg1	Escherichia					70:80	Escherichia	70:80	Escherichia	70:80	Development of Mannopyranoside Therapeutics against Adherent-Invasive Escherichia coli Infections.
30289687	3	138	theme	adherent-invasive	459:475	arg1	infections					477:486	adherent-invasive infections	459:486	adherent-invasive infections in Crohn's disease	459:505	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	4	139	theme	host	615:618	arg1	cells					620:624	host cells	615:624	host cells	615:624	The adhesions of various pathogenic Escherichia coli strains to host cells are primarily mediated through carbohydrate-protein interactions involving bacterial organelles called fimbriae that can recognize specific glycoconjugate receptors on host cells.
30289687	3	140	from	infections	525:534	arg1	disease					499:505	Crohn's disease	491:505	Crohn's disease	491:505	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	3	140	from	infections	525:534	arg1	particular					539:548	particular	539:548	particular	539:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	5	141	gly	glycoproteins	888:900	arg1	glycoproteins					888:900	mannosylated glycoproteins	875:900	mannosylated glycoproteins	875:900	Of particular interest are the FimH and PapG fimbriae, which bind to mannosylated glycoproteins and glycolipids of the galabiose series, respectively.
30289687	2	142	theme	remaining	371:379	arg1	susceptibility					381:394	remaining susceptibility	371:394	remaining susceptibility	371:394	A brief overview of common antibiotic treatments is described in light of their respective resistance and remaining susceptibility.
30289687	13	143	theme	α-C-linked	2384:2393	arg1	mannopyranosides					2395:2410	α-C-linked mannopyranosides	2384:2410	α-C-linked mannopyranosides	2384:2410	This Account primarily concentrates on the most promising types of FimH inhibitors belonging to the family of α-C-linked mannopyranosides.
30289687	16	144	theme	required	2899:2906	arg1	conformation					2918:2929	the required 4C1 chair conformation	2895:2929	the required 4C1 chair conformation	2895:2929	These combined techniques pointed to the fact that several α-C-linked mannopyranosides do exist in the required 4C1 chair conformation.
30289687	3	145	from	disease	499:505	arg1	context					448:454	the context	444:454	the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular	444:548	This strategy has been seriously considered in the context of adherent-invasive infections in Crohn's disease and urinary tract infections in particular.
30289687	7	146	theme	binding	1325:1331	arg1	interactions					1333:1344	the carbohydrate ligand binding interactions	1301:1344	the carbohydrate ligand binding interactions	1301:1344	This is of particular interest since bacterial adhesion to host cells is a parameter unlikely to be the subject of bacterial mutations without affecting the carbohydrate ligand binding interactions at the basis of the recognition and infection processes.
29967448	3	0	theme	mouse	318:322	arg1	model					324:328	our mouse model	314:328	our mouse model of prenatal stress	314:347	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	4	1	theme	Placental	535:543	arg1	function					545:552	Placental function	535:552	Placental function	535:552	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	4	2	theme	neurodevelopmental	745:762	arg1	programming					764:774	neurodevelopmental programming	745:774	neurodevelopmental programming	745:774	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	1	3	from	biases	83:88	arg1	presentation					101:112	disease presentation	93:112	disease presentation	93:112	Although sex biases in disease presentation are well documented, the mechanisms mediating vulnerability or resilience to diseases are unknown.
29967448	6	4	theme	prenatal	1188:1195	arg1	exposure					1204:1211	prenatal stress exposure	1188:1211	prenatal stress exposure	1188:1211	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	6	5	theme	H3K27me3	1082:1089	arg1	levels					1072:1077	high levels	1067:1077	high levels of H3K27me3 in the female placenta	1067:1112	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	3	6	theme	male	350:353	arg1	offspring					355:363	male offspring	350:363	male offspring	350:363	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	6	7	theme	stress	1197:1202	arg1	exposure					1204:1211	prenatal stress exposure	1188:1211	prenatal stress exposure	1188:1211	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	4	8	theme	sex	627:629	arg1	differences					631:641	sex differences	627:641	sex differences in placental O-linked N-acetylglucosamine transferase (OGT)	627:701	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	3	9	theme	stress	342:347	arg1	model					324:328	our mouse model	314:328	our mouse model of prenatal stress	314:347	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	1	10	theme	sex	79:81	arg1	biases					83:88	sex biases	79:88	sex biases in disease presentation	79:112	Although sex biases in disease presentation are well documented, the mechanisms mediating vulnerability or resilience to diseases are unknown.
29967448	4	11	from	effects	715:721	arg1	programming					764:774	neurodevelopmental programming	745:774	neurodevelopmental programming	745:774	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	3	12	theme	stress	450:455	arg1	axis					457:460	hypothalamic pituitary adrenal stress axis	419:460	hypothalamic pituitary adrenal stress axis dysfunction	419:472	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	0	13	theme	prenatal	52:59	arg1	insults					61:67	prenatal insults	52:67	prenatal insults	52:67	Placental H3K27me3 establishes female resilience to prenatal insults.
29967448	6	14	from	levels	1072:1077	arg1	placenta					1105:1112	the female placenta	1094:1112	the female placenta	1094:1112	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	3	15	theme	axis	457:460	arg1	endophenotypes					475:488	endophenotypes	475:488	endophenotypes of male-biased neurodevelopmental disorders	475:532	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	3	15	theme	axis	457:460	arg1	dysfunction					462:472	hypothalamic pituitary adrenal stress axis dysfunction	419:472	hypothalamic pituitary adrenal stress axis dysfunction	419:472	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	5	16	theme	modification	1023:1034	arg1	regulation					971:980	regulation	971:980	regulation of the canonically repressive epigenetic modification, H3K27me3	971:1044	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	3	17	theme	pituitary	432:440	arg1	axis					457:460	hypothalamic pituitary adrenal stress axis	419:460	hypothalamic pituitary adrenal stress axis dysfunction	419:472	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	0	18	theme	Placental	0:8	arg1	H3K27me3					10:17	Placental H3K27me3	0:17	Placental H3K27me3	0:17	Placental H3K27me3 establishes female resilience to prenatal insults.
29967448	6	19	theme	high	1067:1070	arg1	levels					1072:1077	high levels	1067:1077	high levels of H3K27me3 in the female placenta	1067:1112	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	5	20	theme	trophoblast	926:936	arg1	patterns					954:961	sex-specific trophoblast gene expression patterns	913:961	sex-specific trophoblast gene expression patterns	913:961	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	1	21	theme	disease	93:99	arg1	presentation					101:112	disease presentation	93:112	disease presentation	93:112	Although sex biases in disease presentation are well documented, the mechanisms mediating vulnerability or resilience to diseases are unknown.
29967448	3	22	theme	adrenal	442:448	arg1	axis					457:460	hypothalamic pituitary adrenal stress axis	419:460	hypothalamic pituitary adrenal stress axis dysfunction	419:472	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	0	23	theme	female	31:36	arg1	resilience					38:47	female resilience	31:47	female resilience to prenatal insults	31:67	Placental H3K27me3 establishes female resilience to prenatal insults.
29967448	5	24	theme	epigenetic	1012:1021	arg1	H3K27me3					1037:1044	H3K27me3	1037:1044	H3K27me3	1037:1044	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	5	24	theme	epigenetic	1012:1021	arg1	modification					1023:1034	the canonically repressive epigenetic modification	985:1034	the canonically repressive epigenetic modification	985:1034	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	6	25	theme	altered	1139:1145	arg1	programming					1160:1170	the altered hypothalamic programming	1135:1170	the altered hypothalamic programming associated with prenatal stress exposure	1135:1211	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	3	26	theme	long-term	376:384	arg1	dysregulation					386:398	long-term dysregulation	376:398	long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders	376:532	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	6	27	theme	female	1098:1103	arg1	placenta					1105:1112	the female placenta	1094:1112	the female placenta	1094:1112	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	4	28	link	O-linked	656:663	arg1	OGT					698:700	OGT	698:700	OGT	698:700	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	4	28	link	O-linked	656:663	arg1	transferase					685:695	placental O-linked N-acetylglucosamine transferase	646:695	placental O-linked N-acetylglucosamine transferase (OGT)	646:701	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	6	29	theme	hypothalamic	1147:1158	arg1	programming					1160:1170	the altered hypothalamic programming	1135:1170	the altered hypothalamic programming associated with prenatal stress exposure	1135:1211	We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure.
29967448	3	30	theme	dysfunction	462:472	arg1	dysregulation					386:398	long-term dysregulation	376:398	long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders	376:532	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	3	31	theme	hypothalamic	419:430	arg1	axis					457:460	hypothalamic pituitary adrenal stress axis	419:460	hypothalamic pituitary adrenal stress axis dysfunction	419:472	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	4	32	theme	healthy	570:576	arg1	development					584:594	healthy fetal development	570:594	healthy fetal development	570:594	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	5	33	theme	expression	943:952	arg1	patterns					954:961	sex-specific trophoblast gene expression patterns	913:961	sex-specific trophoblast gene expression patterns	913:961	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	5	34	theme	prenatal	877:884	arg1	insults					886:892	prenatal insults	877:892	prenatal insults	877:892	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	5	35	theme	sex-specific	913:924	arg1	patterns					954:961	sex-specific trophoblast gene expression patterns	913:961	sex-specific trophoblast gene expression patterns	913:961	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	3	36	theme	body	403:406	arg1	weight					408:413	body weight	403:413	body weight	403:413	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	4	37	from	differences	631:641	arg1	OGT					698:700	OGT	698:700	OGT	698:700	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	4	37	from	differences	631:641	arg1	transferase					685:695	placental O-linked N-acetylglucosamine transferase	646:695	placental O-linked N-acetylglucosamine transferase (OGT)	646:701	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	5	38	theme	sex	817:819	arg1	differences					821:831	sex differences	817:831	sex differences in OGT	817:838	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	3	39	theme	disorders	524:532	arg1	endophenotypes					475:488	endophenotypes	475:488	endophenotypes of male-biased neurodevelopmental disorders	475:532	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	3	39	theme	disorders	524:532	arg1	dysfunction					462:472	hypothalamic pituitary adrenal stress axis dysfunction	419:472	hypothalamic pituitary adrenal stress axis dysfunction	419:472	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	3	40	theme	weight	408:413	arg1	dysregulation					386:398	long-term dysregulation	376:398	long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders	376:532	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	5	41	from	differences	821:831	arg1	OGT					836:838	OGT	836:838	OGT	836:838	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	4	42	theme	fetal	578:582	arg1	development					584:594	healthy fetal development	570:594	healthy fetal development	570:594	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	2	43	theme	In	213:214	arg1	insults					222:228	In utero insults	213:228	In utero insults	213:228	In utero insults are more likely to produce detrimental health outcomes for males versus females.
29967448	2	44	theme	health	269:274	arg1	outcomes					276:283	detrimental health outcomes	257:283	detrimental health outcomes for males versus females	257:308	In utero insults are more likely to produce detrimental health outcomes for males versus females.
29967448	3	45	theme	male-biased	493:503	arg1	disorders					524:532	male-biased neurodevelopmental disorders	493:532	male-biased neurodevelopmental disorders	493:532	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	4	46	theme	placental	646:654	arg1	OGT					698:700	OGT	698:700	OGT	698:700	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	4	46	theme	placental	646:654	arg1	transferase					685:695	placental O-linked N-acetylglucosamine transferase	646:695	placental O-linked N-acetylglucosamine transferase (OGT)	646:701	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	2	47	theme	detrimental	257:267	arg1	outcomes					276:283	detrimental health outcomes	257:283	detrimental health outcomes for males versus females	257:308	In utero insults are more likely to produce detrimental health outcomes for males versus females.
29967448	3	48	theme	neurodevelopmental	505:522	arg1	disorders					524:532	male-biased neurodevelopmental disorders	493:532	male-biased neurodevelopmental disorders	493:532	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	5	49	theme	repressive	1001:1010	arg1	H3K27me3					1037:1044	H3K27me3	1037:1044	H3K27me3	1037:1044	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	5	49	theme	repressive	1001:1010	arg1	modification					1023:1034	the canonically repressive epigenetic modification	985:1034	the canonically repressive epigenetic modification	985:1034	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	4	50	theme	stress	735:740	arg1	effects					715:721	the effects	711:721	the effects of prenatal stress on neurodevelopmental programming	711:774	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	5	51	theme	gene	938:941	arg1	patterns					954:961	sex-specific trophoblast gene expression patterns	913:961	sex-specific trophoblast gene expression patterns	913:961	Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3.
29967448	4	52	theme	N-acetylglucosamine	665:683	arg1	OGT					698:700	OGT	698:700	OGT	698:700	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	4	52	theme	N-acetylglucosamine	665:683	arg1	transferase					685:695	placental O-linked N-acetylglucosamine transferase	646:695	placental O-linked N-acetylglucosamine transferase (OGT)	646:701	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	3	53	theme	prenatal	333:340	arg1	stress					342:347	prenatal stress	333:347	prenatal stress	333:347	In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders.
29967448	4	54	theme	O-linked	656:663	arg1	OGT					698:700	OGT	698:700	OGT	698:700	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	4	54	theme	O-linked	656:663	arg1	transferase					685:695	placental O-linked N-acetylglucosamine transferase	646:695	placental O-linked N-acetylglucosamine transferase (OGT)	646:701	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	4	55	theme	prenatal	726:733	arg1	stress					735:740	prenatal stress	726:740	prenatal stress	726:740	Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming.
29967448	2	56	dep	In	213:214	arg1	utero					216:220	utero	216:220	utero	216:220	In utero insults are more likely to produce detrimental health outcomes for males versus females.
29941490	7	0	theme	culture	1232:1238	arg1	cells					1240:1244	culture cells	1232:1244	culture cells	1232:1244	OGT inhibition was effective at sensitizing cancer cells to a proteasome inhibitor both in culture cells and a xenograft mouse model.
29941490	4	1	theme	proteins	686:693	arg1	existence					665:673	the possible existence	652:673	the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1	652:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	1	theme	proteins	686:693	arg1	immunoprecipitation					609:627	immunoprecipitation	609:627	immunoprecipitation	609:627	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	7	2	theme	OGT	1141:1143	arg1	inhibition					1145:1154	OGT inhibition	1141:1154	OGT inhibition	1141:1154	OGT inhibition was effective at sensitizing cancer cells to a proteasome inhibitor both in culture cells and a xenograft mouse model.
29941490	2	3	theme	proteasome	342:351	arg1	inhibitors					353:362	proteasome inhibitors	342:362	proteasome inhibitors	342:362	Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors.
29941490	4	4	theme	UPS	585:587	arg1	suppression					570:580	efficient suppression	560:580	efficient suppression of UPS	560:587	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	8	5	theme	metabolism	1327:1336	arg1	O-GlcNAcylation					1288:1302	active O-GlcNAcylation	1281:1302	active O-GlcNAcylation	1281:1302	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	8	5	theme	metabolism	1327:1336	arg1	feature					1309:1315	a feature	1307:1315	a feature of cancer metabolism	1307:1336	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	4	6	link	O-linked	735:742	arg1	transferase					764:774	O-linked N-acetylglucosamine transferase	735:774	O-linked N-acetylglucosamine transferase (OGT)	735:780	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	6	link	O-linked	735:742	arg1	C1					803:804	host cell factor C1	786:804	host cell factor C1 (HCF-1)	786:812	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	6	link	O-linked	735:742	arg1	proteins					821:828	two proteins	817:828	two proteins capable of forming a complex with NRF1	817:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	6	link	O-linked	735:742	arg1	OGT					777:779	OGT	777:779	OGT	777:779	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	8	7	theme	cancer	1387:1392	arg1	metabolism					1394:1403	cancer metabolism	1387:1403	cancer metabolism	1387:1403	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	4	8	theme	cell	791:794	arg1	C1					803:804	host cell factor C1	786:804	host cell factor C1 (HCF-1)	786:812	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	8	theme	cell	791:794	arg1	transferase					764:774	O-linked N-acetylglucosamine transferase	735:774	O-linked N-acetylglucosamine transferase (OGT)	735:780	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	8	theme	cell	791:794	arg1	proteins					821:828	two proteins	817:828	two proteins capable of forming a complex with NRF1	817:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	8	theme	cell	791:794	arg1	HCF-1					807:811	HCF-1	807:811	HCF-1	807:811	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	5	9	theme	consequent	944:953	arg1	upregulation					955:966	consequent upregulation	944:966	consequent upregulation of proteasome subunit genes	944:994	O-GlcNAcylation catalyzed by OGT was essential for NRF1 stabilization and consequent upregulation of proteasome subunit genes.
29941490	5	10	theme	NRF1	921:924	arg1	stabilization					926:938	NRF1 stabilization	921:938	NRF1 stabilization	921:938	O-GlcNAcylation catalyzed by OGT was essential for NRF1 stabilization and consequent upregulation of proteasome subunit genes.
29941490	7	11	theme	mouse	1262:1266	arg1	model					1268:1272	a xenograft mouse model	1250:1272	a xenograft mouse model	1250:1272	OGT inhibition was effective at sensitizing cancer cells to a proteasome inhibitor both in culture cells and a xenograft mouse model.
29941490	6	12	theme	OGT	1112:1114	arg1	abundance					1099:1107	the relative protein abundance	1078:1107	the relative protein abundance of OGT and proteasome subunits	1078:1138	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	7	13	theme	proteasome	1203:1212	arg1	inhibitor					1214:1222	a proteasome inhibitor	1201:1222	a proteasome inhibitor	1201:1222	OGT inhibition was effective at sensitizing cancer cells to a proteasome inhibitor both in culture cells and a xenograft mouse model.
29941490	4	14	theme	capable	830:836	arg1	transferase					764:774	O-linked N-acetylglucosamine transferase	735:774	O-linked N-acetylglucosamine transferase (OGT)	735:780	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	14	theme	capable	830:836	arg1	C1					803:804	host cell factor C1	786:804	host cell factor C1 (HCF-1)	786:812	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	14	theme	capable	830:836	arg1	proteins					821:828	two proteins	817:828	two proteins capable of forming a complex with NRF1	817:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	2	15	theme	cancer	275:280	arg1	cells					282:286	cancer cells	275:286	cancer cells	275:286	Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors.
29941490	6	16	theme	relative	1082:1089	arg1	abundance					1099:1107	the relative protein abundance	1078:1107	the relative protein abundance of OGT and proteasome subunits	1078:1138	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	4	17	theme	possible	656:663	arg1	existence					665:673	the possible existence	652:673	the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1	652:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	17	theme	possible	656:663	arg1	immunoprecipitation					609:627	immunoprecipitation	609:627	immunoprecipitation	609:627	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	8	18	theme	proteasome	1479:1488	arg1	activity					1490:1497	the proteasome activity	1475:1497	the proteasome activity	1475:1497	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	0	19	from	Resistance	53:62	arg1	Cells					74:78	Cancer Cells	67:78	Cancer Cells	67:78	O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1.
29941490	5	20	theme	subunit	982:988	arg1	genes					990:994	proteasome subunit genes	971:994	proteasome subunit genes	971:994	O-GlcNAcylation catalyzed by OGT was essential for NRF1 stabilization and consequent upregulation of proteasome subunit genes.
29941490	2	21	from	dependence	236:245	arg1	activity					265:272	the proteasome activity	250:272	the proteasome activity	250:272	Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors.
29941490	6	22	theme	protein	1091:1097	arg1	abundance					1099:1107	the relative protein abundance	1078:1107	the relative protein abundance of OGT and proteasome subunits	1078:1138	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	8	23	theme	cancer	1320:1325	arg1	metabolism					1327:1336	cancer metabolism	1320:1336	cancer metabolism	1320:1336	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	2	24	theme	multiple	300:307	arg1	myeloma					309:315	multiple myeloma	300:315	multiple myeloma	300:315	Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors.
29941490	4	25	theme	N-acetylglucosamine	744:762	arg1	transferase					764:774	O-linked N-acetylglucosamine transferase	735:774	O-linked N-acetylglucosamine transferase (OGT)	735:780	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	25	theme	N-acetylglucosamine	744:762	arg1	C1					803:804	host cell factor C1	786:804	host cell factor C1 (HCF-1)	786:812	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	25	theme	N-acetylglucosamine	744:762	arg1	proteins					821:828	two proteins	817:828	two proteins capable of forming a complex with NRF1	817:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	25	theme	N-acetylglucosamine	744:762	arg1	OGT					777:779	OGT	777:779	OGT	777:779	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	3	26	theme	proteasome	405:414	arg1	response					428:435	the proteasome bounce-back response	401:435	the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes	401:529	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	3	26	theme	proteasome	405:414	arg1	cause					373:377	A major cause	365:377	A major cause of this resistance	365:396	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	0	27	theme	O-GlcNAcylation	0:14	arg1	Signal					16:21	O-GlcNAcylation Signal	0:21	O-GlcNAcylation Signal	0:21	O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1.
29941490	7	28	dep	sensitizing	1173:1183	arg1	both					1224:1227	both	1224:1227	both	1224:1227	OGT inhibition was effective at sensitizing cancer cells to a proteasome inhibitor both in culture cells and a xenograft mouse model.
29941490	1	29	theme	Cancer	101:106	arg1	cells					108:112	Cancer cells	101:112	Cancer cells	101:112	Cancer cells often heavily depend on the ubiquitin-proteasome system (UPS) for their growth and survival.
29941490	8	30	theme	novel	1365:1369	arg1	linkage					1371:1377	a novel linkage	1363:1377	a novel linkage between cancer metabolism and UPS function	1363:1420	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	3	31	theme	bounce-back	416:426	arg1	response					428:435	the proteasome bounce-back response	401:435	the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes	401:529	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	3	31	theme	bounce-back	416:426	arg1	cause					373:377	A major cause	365:377	A major cause of this resistance	365:396	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	0	32	theme	Proteasome	32:41	arg1	Resistance					53:62	Proteasome Inhibitor Resistance	32:62	Proteasome Inhibitor Resistance in Cancer Cells	32:78	O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1.
29941490	4	33	theme	O-linked	735:742	arg1	transferase					764:774	O-linked N-acetylglucosamine transferase	735:774	O-linked N-acetylglucosamine transferase (OGT)	735:780	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	33	theme	O-linked	735:742	arg1	C1					803:804	host cell factor C1	786:804	host cell factor C1 (HCF-1)	786:812	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	33	theme	O-linked	735:742	arg1	proteins					821:828	two proteins	817:828	two proteins capable of forming a complex with NRF1	817:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	33	theme	O-linked	735:742	arg1	OGT					777:779	OGT	777:779	OGT	777:779	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	6	34	from	correlations	1062:1073	arg1	abundance					1099:1107	the relative protein abundance	1078:1107	the relative protein abundance of OGT and proteasome subunits	1078:1138	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	8	35	theme	UPS	1409:1411	arg1	function					1413:1420	UPS function	1409:1420	UPS function	1409:1420	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	4	36	theme	mass	633:636	arg1	spectrometry					638:649	mass spectrometry	633:649	mass spectrometry	633:649	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	3	37	theme	major	367:371	arg1	cause					373:377	A major cause	365:377	A major cause of this resistance	365:396	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	3	37	theme	major	367:371	arg1	response					428:435	the proteasome bounce-back response	401:435	the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes	401:529	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	4	38	theme	host	786:789	arg1	C1					803:804	host cell factor C1	786:804	host cell factor C1 (HCF-1)	786:812	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	38	theme	host	786:789	arg1	transferase					764:774	O-linked N-acetylglucosamine transferase	735:774	O-linked N-acetylglucosamine transferase (OGT)	735:780	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	38	theme	host	786:789	arg1	proteins					821:828	two proteins	817:828	two proteins capable of forming a complex with NRF1	817:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	38	theme	host	786:789	arg1	HCF-1					807:811	HCF-1	807:811	HCF-1	807:811	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	3	39	theme	proteasome	506:515	arg1	genes					525:529	proteasome subunit genes	506:529	proteasome subunit genes	506:529	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	1	40	theme	ubiquitin-proteasome	142:161	arg1	system					163:168	the ubiquitin-proteasome system	138:168	the ubiquitin-proteasome system (UPS) for their growth and survival	138:204	Cancer cells often heavily depend on the ubiquitin-proteasome system (UPS) for their growth and survival.
29941490	1	40	theme	ubiquitin-proteasome	142:161	arg1	UPS					171:173	UPS	171:173	UPS	171:173	Cancer cells often heavily depend on the ubiquitin-proteasome system (UPS) for their growth and survival.
29941490	4	41	theme	efficient	560:568	arg1	suppression					570:580	efficient suppression	560:580	efficient suppression of UPS	560:587	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	2	42	theme	dependence	236:245	arg1	Irrespective					207:218	Irrespective	207:218	Irrespective	207:218	Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors.
29941490	6	43	theme	positive	1053:1060	arg1	correlations					1062:1073	positive correlations	1053:1073	positive correlations in the relative protein abundance of OGT and proteasome subunits	1053:1138	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	0	44	theme	Inhibitor	43:51	arg1	Resistance					53:62	Proteasome Inhibitor Resistance	32:62	Proteasome Inhibitor Resistance in Cancer Cells	32:78	O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1.
29941490	2	45	theme	strong	229:234	arg1	dependence					236:245	their strong dependence	223:245	their strong dependence on the proteasome activity	223:272	Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors.
29941490	0	46	theme	Cancer	67:72	arg1	Cells					74:78	Cancer Cells	67:78	Cancer Cells	67:78	O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1.
29941490	6	47	theme	proteasome	1120:1129	arg1	subunits					1131:1138	proteasome subunits	1120:1138	proteasome subunits	1120:1138	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	3	48	theme	resistance	387:396	arg1	cause					373:377	A major cause	365:377	A major cause of this resistance	365:396	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	3	48	theme	resistance	387:396	arg1	response					428:435	the proteasome bounce-back response	401:435	the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes	401:529	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	4	49	theme	new	544:546	arg1	targets					548:554	new targets	544:554	new targets for efficient suppression of UPS	544:587	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	7	50	theme	cancer	1185:1190	arg1	cells					1192:1196	cancer cells	1185:1196	cancer cells	1185:1196	OGT inhibition was effective at sensitizing cancer cells to a proteasome inhibitor both in culture cells and a xenograft mouse model.
29941490	5	51	theme	genes	990:994	arg1	stabilization					926:938	NRF1 stabilization	921:938	NRF1 stabilization	921:938	O-GlcNAcylation catalyzed by OGT was essential for NRF1 stabilization and consequent upregulation of proteasome subunit genes.
29941490	5	51	theme	genes	990:994	arg1	upregulation					955:966	consequent upregulation	944:966	consequent upregulation of proteasome subunit genes	944:994	O-GlcNAcylation catalyzed by OGT was essential for NRF1 stabilization and consequent upregulation of proteasome subunit genes.
29941490	4	52	theme	factor	796:801	arg1	C1					803:804	host cell factor C1	786:804	host cell factor C1 (HCF-1)	786:812	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	52	theme	factor	796:801	arg1	transferase					764:774	O-linked N-acetylglucosamine transferase	735:774	O-linked N-acetylglucosamine transferase (OGT)	735:780	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	52	theme	factor	796:801	arg1	proteins					821:828	two proteins	817:828	two proteins capable of forming a complex with NRF1	817:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	4	52	theme	factor	796:801	arg1	HCF-1					807:811	HCF-1	807:811	HCF-1	807:811	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	3	53	theme	transcription	457:469	arg1	NRF1					449:452	NRF1	449:452	NRF1	449:452	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	3	53	theme	transcription	457:469	arg1	factor					471:476	a transcription factor	455:476	a transcription factor that coordinately activates proteasome subunit genes	455:529	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	6	54	theme	cancers	1036:1042	arg1	Meta-analysis					997:1009	Meta-analysis	997:1009	Meta-analysis of breast and colorectal cancers	997:1042	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	8	55	theme	activity	1490:1497	arg1	regulation					1461:1470	the regulation	1457:1470	the regulation of the proteasome activity	1457:1497	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	2	56	theme	proteasome	254:263	arg1	activity					265:272	the proteasome activity	250:272	the proteasome activity	250:272	Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors.
29941490	6	57	theme	subunits	1131:1138	arg1	abundance					1099:1107	the relative protein abundance	1078:1107	the relative protein abundance of OGT and proteasome subunits	1078:1138	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	4	58	with	complex	851:857	arg1	NRF1					864:867	NRF1	864:867	NRF1	864:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	6	59	theme	colorectal	1025:1034	arg1	cancers					1036:1042	breast and colorectal cancers	1014:1042	cancers	1036:1042	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
29941490	5	60	theme	proteasome	971:980	arg1	genes					990:994	proteasome subunit genes	971:994	proteasome subunit genes	971:994	O-GlcNAcylation catalyzed by OGT was essential for NRF1 stabilization and consequent upregulation of proteasome subunit genes.
29941490	8	61	theme	regulatory	1438:1447	arg1	axis					1449:1452	a new regulatory axis	1432:1452	a new regulatory axis	1432:1452	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	8	62	theme	active	1281:1286	arg1	O-GlcNAcylation					1288:1302	active O-GlcNAcylation	1281:1302	active O-GlcNAcylation	1281:1302	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	8	62	theme	active	1281:1286	arg1	feature					1309:1315	a feature	1307:1315	a feature of cancer metabolism	1307:1336	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	3	63	theme	subunit	517:523	arg1	genes					525:529	proteasome subunit genes	506:529	proteasome subunit genes	506:529	A major cause of this resistance is the proteasome bounce-back response mediated by NRF1, a transcription factor that coordinately activates proteasome subunit genes.
29941490	8	64	theme	new	1434:1436	arg1	axis					1449:1452	a new regulatory axis	1432:1452	a new regulatory axis	1432:1452	Since active O-GlcNAcylation is a feature of cancer metabolism, our study has clarified a novel linkage between cancer metabolism and UPS function and added a new regulatory axis to the regulation of the proteasome activity.
29941490	4	65	theme	nuclear	678:684	arg1	proteins					686:693	nuclear proteins	678:693	nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1	678:867	To identify new targets for efficient suppression of UPS, we explored, using immunoprecipitation and mass spectrometry, the possible existence of nuclear proteins that cooperate with NRF1 and identified O-linked N-acetylglucosamine transferase (OGT) and host cell factor C1 (HCF-1) as two proteins capable of forming a complex with NRF1.
29941490	7	66	theme	xenograft	1252:1260	arg1	model					1268:1272	a xenograft mouse model	1250:1272	a xenograft mouse model	1250:1272	OGT inhibition was effective at sensitizing cancer cells to a proteasome inhibitor both in culture cells and a xenograft mouse model.
29941490	6	67	theme	breast	1014:1019	arg1	cancers					1036:1042	breast and colorectal cancers	1014:1042	cancers	1036:1042	Meta-analysis of breast and colorectal cancers revealed positive correlations in the relative protein abundance of OGT and proteasome subunits.
28742148	8	0	theme	OGT	1552:1554	arg1	activity					1556:1563	OGT activity	1552:1563	OGT activity	1552:1563	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	13	1	theme	O-GlcNAcylation	2077:2091	arg1	pathway					2093:2099	the O-GlcNAcylation pathway	2073:2099	the O-GlcNAcylation pathway	2073:2099	These findings reveal the interplay between Tax and the O-GlcNAcylation pathway and identify new key molecular actors involved in the assembly of the Tax-dependent transactivation complex.
28742148	7	2	theme	active	1350:1355	arg1	form					1357:1360	a less active form	1343:1360	a less active form of OGA	1343:1367	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	1	3	theme	adult	255:259	arg1	leukemia					268:275	adult T-cell leukemia	255:275	adult T-cell leukemia	255:275	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	6	4	theme	HTLV-1-transformed	1099:1116	arg1	cells					1120:1124	HTLV-1-transformed T cells	1099:1124	HTLV-1-transformed T cells	1099:1124	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	11	5	theme	LTR	1948:1950	arg1	transactivation					1952:1966	Tax-mediated LTR transactivation	1935:1966	Tax-mediated LTR transactivation	1935:1966	Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation.
28742148	1	6	theme	T-cell	158:163	arg1	type					184:187	Human T-cell lymphotropic virus type 1	152:189	Human T-cell lymphotropic virus type 1 (HTLV-1)-replication	152:210	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	1	6	theme	T-cell	158:163	arg1	HTLV-1					192:197	HTLV-1	192:197	HTLV-1	192:197	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	7	7	theme	OGA	1365:1367	arg1	form					1357:1360	a less active form	1343:1360	a less active form of OGA	1343:1367	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	9	8	theme	OGT/OGA	1602:1608	arg1	complex					1610:1616	the OGT/OGA complex	1598:1616	the OGT/OGA complex	1598:1616	Furthermore, Tax interacts with the OGT/OGA complex and inhibits the activity of OGT-bound OGA.
28742148	2	9	from	LTR	325:327	arg1	transcription					294:306	the transcription	290:306	the transcription from the viral 5'LTR	290:327	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	6	10	theme	OGT	1168:1170	arg1	expression					1172:1181	OGT expression	1168:1181	OGT expression	1168:1181	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	1	11	theme	virus	178:182	arg1	type					184:187	Human T-cell lymphotropic virus type 1	152:189	Human T-cell lymphotropic virus type 1 (HTLV-1)-replication	152:210	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	1	11	theme	virus	178:182	arg1	HTLV-1					192:197	HTLV-1	192:197	HTLV-1	192:197	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	6	12	theme	T	1149:1149	arg1	lines					1156:1160	control T cell lines	1141:1160	control T cell lines	1141:1160	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	7	13	theme	T	1313:1313	arg1	cells					1315:1319	HTLV-1-transformed T cells	1294:1319	HTLV-1-transformed T cells	1294:1319	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	5	14	theme	T	1020:1020	arg1	cells					1022:1026	HTLV-1-transformed T cells	1001:1026	HTLV-1-transformed T cells	1001:1026	In this study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells.
28742148	0	15	theme	O-GlcNAcZYME	17:28	arg1	complex					30:36	the O-GlcNAcZYME complex	13:36	the O-GlcNAcZYME complex	13:36	Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.
28742148	6	16	theme	cell	1151:1154	arg1	lines					1156:1160	control T cell lines	1141:1160	control T cell lines	1141:1160	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	4	17	from	O-GlcNAc	866:873	arg1	proteins					878:885	proteins	878:885	proteins	878:885	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	9	18	theme	OGA	1657:1659	arg1	activity					1635:1642	the activity	1631:1642	the activity of OGT-bound OGA	1631:1659	Furthermore, Tax interacts with the OGT/OGA complex and inhibits the activity of OGT-bound OGA.
28742148	3	19	theme	reversible	568:577	arg1	modification					598:609	another reversible post-translational modification	560:609	another reversible post-translational modification involved in a wide range of diseases, including cancers	560:665	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	3	19	theme	reversible	568:577	arg1	O-GlcNAcylation					543:557	O-GlcNAcylation	543:557	O-GlcNAcylation	543:557	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	6	20	theme	control	1141:1147	arg1	lines					1156:1160	control T cell lines	1141:1160	control T cell lines	1141:1160	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	5	21	theme	O-GlcNAcylation	974:988	arg1	enzymes					990:996	O-GlcNAcylation enzymes	974:996	O-GlcNAcylation enzymes	974:996	In this study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells.
28742148	3	22	theme	post-translational	579:596	arg1	modification					598:609	another reversible post-translational modification	560:609	another reversible post-translational modification involved in a wide range of diseases, including cancers	560:665	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	3	22	theme	post-translational	579:596	arg1	O-GlcNAcylation					543:557	O-GlcNAcylation	543:557	O-GlcNAcylation	543:557	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	13	23	theme	transactivation	2185:2199	arg1	complex					2201:2207	the Tax-dependent transactivation complex	2167:2207	the Tax-dependent transactivation complex	2167:2207	These findings reveal the interplay between Tax and the O-GlcNAcylation pathway and identify new key molecular actors involved in the assembly of the Tax-dependent transactivation complex.
28742148	8	24	theme	HEK-293T	1391:1398	arg1	cells					1400:1404	HEK-293T cells	1391:1404	HEK-293T cells	1391:1404	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	7	25	theme	specific	1262:1269	arg1	activity					1271:1278	OGA specific activity	1258:1278	OGA specific activity	1258:1278	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	0	26	theme	Tax	52:54	arg1	oncoprotein					56:66	the HTLV-1 Tax oncoprotein	41:66	the HTLV-1 Tax oncoprotein	41:66	Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.
28742148	11	27	theme	O-GlcNAcylation	1905:1919	arg1	site					1921:1924	a previously described O-GlcNAcylation site	1882:1924	a previously described O-GlcNAcylation site	1882:1924	Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation.
28742148	4	28	from	Threonine	765:773	arg1	addition					700:707	the addition	696:707	the addition	696:707	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	13	29	theme	complex	2201:2207	arg1	assembly					2155:2162	the assembly	2151:2162	the assembly of the Tax-dependent transactivation complex	2151:2207	These findings reveal the interplay between Tax and the O-GlcNAcylation pathway and identify new key molecular actors involved in the assembly of the Tax-dependent transactivation complex.
28742148	4	30	from	Serine	755:760	arg1	addition					700:707	the addition	696:707	the addition	696:707	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	8	31	theme	HTLV-1-transformed	1422:1439	arg1	cells					1450:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	10	32	theme	HTLV-1-LTR	1738:1747	arg1	transactivation					1749:1763	HTLV-1-LTR transactivation	1738:1763	CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR	1706:1802	Pharmacological inhibition of OGA increases CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR.
28742148	7	33	theme	form	1357:1360	arg1	level					1334:1338	high level	1329:1338	high level of a less active form of OGA	1329:1367	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	8	34	theme	T	1448:1448	arg1	cells					1450:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	11	35	theme	CREB	1843:1846	arg1	overexpression					1815:1828	overexpression	1815:1828	overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site	1815:1924	Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation.
28742148	7	36	theme	OGA	1258:1260	arg1	activity					1271:1278	OGA specific activity	1258:1278	OGA specific activity	1258:1278	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	2	37	theme	CREB	416:419	arg1	dimers					391:396	dimers	391:396	dimers of phosphorylated CREB	391:419	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	2	38	theme	own	352:354	arg1	expression					356:365	thereby its own expression	340:365	thereby its own expression	340:365	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	1	39	theme	T-cell	261:266	arg1	leukemia					268:275	adult T-cell leukemia	255:275	adult T-cell leukemia	255:275	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	11	40	theme	CREB	1858:1861	arg1	protein					1863:1869	a CREB protein	1856:1869	overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site	1815:1924	Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation.
28742148	1	41	theme	viral	105:109	arg1	oncoprotein					115:125	The viral Tax oncoprotein	101:125	The viral Tax oncoprotein	101:125	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	1	42	theme	key	135:137	arg1	role					139:142	a key role	133:142	a key role	133:142	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	2	43	theme	located	447:453	arg1	elements					438:445	cAMP-response elements	424:445	cAMP-response elements located within the U3 region (vCRE)	424:481	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	8	44	theme	OGA	1481:1483	arg1	activity					1485:1492	OGA activity	1481:1492	OGA activity	1481:1492	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	0	45	theme	complex	30:36	arg1	Hijacking					0:8	Hijacking	0:8	Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein	0:66	Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.
28742148	2	46	theme	cAMP-response	424:436	arg1	elements					438:445	cAMP-response elements	424:445	cAMP-response elements located within the U3 region (vCRE)	424:481	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	7	47	theme	higher	1206:1211	arg1	production					1217:1226	higher OGA production	1206:1226	higher OGA production	1206:1226	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	8	48	theme	total	1507:1511	arg1	O-GlcNAcylation					1513:1527	total O-GlcNAcylation	1507:1527	total O-GlcNAcylation	1507:1527	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	3	49	theme	diseases	639:646	arg1	cancers					659:665	cancers	659:665	cancers	659:665	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	3	49	theme	diseases	639:646	arg1	range					630:634	a wide range	623:634	a wide range of diseases, including cancers	623:665	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	2	50	theme	viral	317:321	arg1	LTR					325:327	the viral 5'LTR	313:327	the viral 5'LTR	313:327	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	10	51	theme	Pharmacological	1662:1676	arg1	inhibition					1678:1687	Pharmacological inhibition	1662:1687	Pharmacological inhibition of OGA	1662:1694	Pharmacological inhibition of OGA increases CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR.
28742148	6	52	theme	OGA	1043:1045	arg1	mRNA					1047:1050	OGA mRNA	1043:1050	OGA mRNA	1043:1050	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	13	53	theme	key	2118:2120	arg1	actors					2132:2137	new key molecular actors	2114:2137	new key molecular actors involved in the assembly of the Tax-dependent transactivation complex	2114:2207	These findings reveal the interplay between Tax and the O-GlcNAcylation pathway and identify new key molecular actors involved in the assembly of the Tax-dependent transactivation complex.
28742148	5	54	from	status	964:969	arg1	cells					1022:1026	HTLV-1-transformed T cells	1001:1026	HTLV-1-transformed T cells	1001:1026	In this study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells.
28742148	4	55	theme	O-GlcNAc	822:829	arg1	OGT					844:846	OGT	844:846	OGT	844:846	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	55	theme	O-GlcNAc	822:829	arg1	enzymes					813:819	two enzymes	809:819	two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA)	809:908	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	55	theme	O-GlcNAc	822:829	arg1	transferase					831:841	O-GlcNAc transferase	822:841	O-GlcNAc transferase (OGT)	822:847	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	10	56	theme	OGA	1692:1694	arg1	inhibition					1678:1687	Pharmacological inhibition	1662:1687	Pharmacological inhibition of OGA	1662:1694	Pharmacological inhibition of OGA increases CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR.
28742148	6	57	theme	T	1118:1118	arg1	cells					1120:1124	HTLV-1-transformed T cells	1099:1124	HTLV-1-transformed T cells	1099:1124	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	11	58	theme	Tax-mediated	1935:1946	arg1	transactivation					1952:1966	Tax-mediated LTR transactivation	1935:1966	Tax-mediated LTR transactivation	1935:1966	Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation.
28742148	1	59	theme	Human	152:156	arg1	type					184:187	Human T-cell lymphotropic virus type 1	152:189	Human T-cell lymphotropic virus type 1 (HTLV-1)-replication	152:210	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	1	59	theme	Human	152:156	arg1	HTLV-1					192:197	HTLV-1	192:197	HTLV-1	192:197	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	1	60	theme	lymphotropic	165:176	arg1	type					184:187	Human T-cell lymphotropic virus type 1	152:189	Human T-cell lymphotropic virus type 1 (HTLV-1)-replication	152:210	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	1	60	theme	lymphotropic	165:176	arg1	HTLV-1					192:197	HTLV-1	192:197	HTLV-1	192:197	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	8	61	from	change	1542:1547	arg1	activity					1556:1563	OGT activity	1552:1563	OGT activity	1552:1563	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	10	62	theme	CREB	1706:1709	arg1	O-GlcNAcylation					1711:1725	CREB O-GlcNAcylation	1706:1725	CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR	1706:1802	Pharmacological inhibition of OGA increases CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR.
28742148	1	63	theme	type	184:187	arg1	-replication					199:210	Human T-cell lymphotropic virus type 1 (HTLV-1)-replication	152:210	Human T-cell lymphotropic virus type 1 (HTLV-1)-replication	152:210	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	7	64	theme	high	1329:1332	arg1	level					1334:1338	high level	1329:1338	high level of a less active form of OGA	1329:1367	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	5	65	theme	HTLV-1-transformed	1001:1018	arg1	cells					1022:1026	HTLV-1-transformed T cells	1001:1026	HTLV-1-transformed T cells	1001:1026	In this study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells.
28742148	1	66	theme	Tax	111:113	arg1	oncoprotein					115:125	The viral Tax oncoprotein	101:125	The viral Tax oncoprotein	101:125	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28742148	9	67	theme	OGT-bound	1647:1655	arg1	OGA					1657:1659	OGT-bound OGA	1647:1659	OGT-bound OGA	1647:1659	Furthermore, Tax interacts with the OGT/OGA complex and inhibits the activity of OGT-bound OGA.
28742148	7	68	theme	HTLV-1-transformed	1294:1311	arg1	cells					1315:1319	HTLV-1-transformed T cells	1294:1319	HTLV-1-transformed T cells	1294:1319	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	10	69	theme	CREB	1776:1779	arg1	recruitment					1781:1791	CREB recruitment	1776:1791	CREB recruitment to the LTR	1776:1802	Pharmacological inhibition of OGA increases CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR.
28742148	5	70	theme	enzymes	990:996	arg1	status					964:969	the status	960:969	the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells	960:1026	In this study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells.
28742148	11	71	theme	described	1895:1903	arg1	site					1921:1924	a previously described O-GlcNAcylation site	1882:1924	a previously described O-GlcNAcylation site	1882:1924	Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation.
28742148	4	72	dep	Serine	755:760	arg1	residues					775:782	residues	775:782	residues	775:782	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	2	73	theme	U3	466:467	arg1	vCRE					477:480	vCRE	477:480	vCRE	477:480	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	2	73	theme	U3	466:467	arg1	region					469:474	the U3 region	462:474	the U3 region (vCRE)	462:481	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	8	74	theme	Tax-negative	1409:1420	arg1	cells					1450:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	0	75	theme	viral	80:84	arg1	transcription					86:98	viral transcription	80:98	viral transcription	80:98	Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.
28742148	8	76	theme	TL-om1	1441:1446	arg1	cells					1450:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Tax-negative HTLV-1-transformed TL-om1 T cells	1409:1454	Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity.
28742148	6	77	theme	expression	1064:1073	arg1	levels					1075:1080	OGA mRNA and protein expression levels	1043:1080	OGA mRNA and protein expression levels	1043:1080	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	4	78	from	O-linked-N-acetylglucosamine	712:739	arg1	Threonine					765:773	Threonine	765:773	Threonine	765:773	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	78	from	O-linked-N-acetylglucosamine	712:739	arg1	Serine					755:760	Serine	755:760	Serine	755:760	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	2	79	theme	phosphorylated	401:414	arg1	CREB					416:419	phosphorylated CREB	401:419	phosphorylated CREB	401:419	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	11	80	theme	wild-type	1833:1841	arg1	CREB					1843:1846	wild-type CREB	1833:1846	wild-type CREB	1833:1846	Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation.
28742148	4	81	dep	enzymes	813:819	arg1	OGA					905:907	OGA	905:907	OGA	905:907	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	81	dep	enzymes	813:819	arg1	O-GlcNAcase					892:902	O-GlcNAcase	892:902	O-GlcNAcase (OGA)	892:908	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	81	dep	enzymes	813:819	arg1	OGT					844:846	OGT	844:846	OGT	844:846	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	81	dep	enzymes	813:819	arg1	enzymes					813:819	two enzymes	809:819	two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA)	809:908	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	81	dep	enzymes	813:819	arg1	transferase					831:841	O-GlcNAc transferase	822:841	O-GlcNAc transferase (OGT)	822:847	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	82	from	addition	700:707	arg1	Threonine					765:773	Threonine	765:773	Threonine	765:773	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	4	82	from	addition	700:707	arg1	Serine					755:760	Serine	755:760	Serine	755:760	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	2	83	theme	dimers	391:396	arg1	recruitment					376:386	the recruitment	372:386	the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE)	372:481	Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE).
28742148	4	84	theme	O-linked-N-acetylglucosamine	712:739	arg1	addition					700:707	the addition	696:707	the addition	696:707	O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it.
28742148	13	85	theme	Tax-dependent	2171:2183	arg1	complex					2201:2207	the Tax-dependent transactivation complex	2167:2207	the Tax-dependent transactivation complex	2167:2207	These findings reveal the interplay between Tax and the O-GlcNAcylation pathway and identify new key molecular actors involved in the assembly of the Tax-dependent transactivation complex.
28742148	7	86	theme	OGA	1213:1215	arg1	production					1217:1226	higher OGA production	1206:1226	higher OGA production	1206:1226	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	0	87	theme	HTLV-1	45:50	arg1	oncoprotein					56:66	the HTLV-1 Tax oncoprotein	41:66	the HTLV-1 Tax oncoprotein	41:66	Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.
28742148	6	88	theme	protein	1056:1062	arg1	expression					1064:1073	protein expression	1056:1073	protein expression	1056:1073	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	3	89	theme	O-GlcNAcylation	543:557	arg1	CREB					516:519	CREB	516:519	CREB	516:519	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	3	89	theme	O-GlcNAcylation	543:557	arg1	target					533:538	the target	529:538	the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers	529:665	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	6	90	theme	mRNA	1047:1050	arg1	levels					1075:1080	OGA mRNA and protein expression levels	1043:1080	OGA mRNA and protein expression levels	1043:1080	We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged.
28742148	3	91	theme	wide	625:628	arg1	cancers					659:665	cancers	659:665	cancers	659:665	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	3	91	theme	wide	625:628	arg1	range					630:634	a wide range	623:634	a wide range of diseases, including cancers	623:665	In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers.
28742148	13	92	theme	new	2114:2116	arg1	actors					2132:2137	new key molecular actors	2114:2137	new key molecular actors involved in the assembly of the Tax-dependent transactivation complex	2114:2207	These findings reveal the interplay between Tax and the O-GlcNAcylation pathway and identify new key molecular actors involved in the assembly of the Tax-dependent transactivation complex.
28742148	7	93	from	reduction	1245:1253	arg1	activity					1271:1278	OGA specific activity	1258:1278	OGA specific activity	1258:1278	However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA.
28742148	13	94	theme	molecular	2122:2130	arg1	actors					2132:2137	new key molecular actors	2114:2137	new key molecular actors involved in the assembly of the Tax-dependent transactivation complex	2114:2207	These findings reveal the interplay between Tax and the O-GlcNAcylation pathway and identify new key molecular actors involved in the assembly of the Tax-dependent transactivation complex.
28742148	1	95	theme	HTLV-1-associated	216:232	arg1	pathologies					234:244	HTLV-1-associated pathologies	216:244	HTLV-1-associated pathologies	216:244	The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia.
28661453	7	0	theme	ChREBPα	1395:1401	arg1	activity					1403:1410	ChREBPα activity	1395:1410	ChREBPα activity upon fructose feeding	1395:1432	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	8	1	theme	activity	1532:1539	arg1	LXRα					1466:1469	LXRα	1466:1469	LXRα	1466:1469	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	8	1	theme	activity	1532:1539	arg1	regulator					1487:1495	an important regulator	1474:1495	an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose	1474:1552	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	2	2	theme	reduced	321:327	arg1	signaling					393:401	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	6	3	theme	ChREBPα	1104:1110	arg1	activity					1112:1119	reduced ChREBPα activity	1096:1119	reduced ChREBPα activity in glucose fed, but not fructose fed mice	1096:1161	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	1	4	theme	hepatic	244:250	arg1	lipogenesis					260:270	hepatic de novo lipogenesis	244:270	hepatic de novo lipogenesis	244:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	2	5	link	O-linked	353:360	arg1	O-GlcNAc					383:390	O-GlcNAc	383:390	O-GlcNAc	383:390	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	5	link	O-linked	353:360	arg1	N-acetylglucosamine					362:380	feeding-induced nuclear O-linked N-acetylglucosamine	329:380	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	4	6	from	mice	895:898	arg1	metabolism					763:772	hepatic carbohydrate metabolism	742:772	hepatic carbohydrate metabolism	742:772	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	6	from	mice	895:898	arg1	livers					807:812	livers	807:812	livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	807:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	6	from	mice	895:898	arg1	expression					793:802	lipogenic gene expression	778:802	lipogenic gene expression	778:802	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	1	7	theme	response	148:155	arg1	ChREBPα/β					183:191	ChREBPα/β	183:191	ChREBPα/β	183:191	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	7	theme	response	148:155	arg1	proteins					173:180	carbohydrate response element-binding proteins	135:180	carbohydrate response element-binding proteins (ChREBPα/β)	135:192	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	7	theme	response	148:155	arg1	players					202:208	key players	198:208	key players in the transcriptional control of hepatic de novo lipogenesis	198:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	7	theme	response	148:155	arg1	receptors					112:120	Liver X receptors	104:120	Liver X receptors (LXRα/β)	104:129	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	6	8	theme	Chrebpβ	1076:1082	arg1	expression					1029:1038	lower expression	1023:1038	lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ	1023:1082	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	6	9	theme	fed	1154:1156	arg1	mice					1158:1161	glucose fed, but not fructose fed mice	1124:1161	glucose fed, but not fructose fed mice	1124:1161	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	2	10	theme	knockout	287:294	arg1	mice					311:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	11	theme	lipid	541:545	arg1	synthesis					547:555	lipid synthesis	541:555	lipid synthesis	541:555	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	12	theme	LXRα/β	273:278	arg1	mice					311:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	4	13	theme	knockout	876:883	arg1	mice					895:898	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	mice	895:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	7	14	theme	glucose-6-phosphatase	1286:1306	arg1	expression					1315:1324	increased glucose-6-phosphatase (G6pc) expression	1276:1324	increased glucose-6-phosphatase (G6pc) expression	1276:1324	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	3	15	theme	LXRs	579:582	arg1	role					571:574	the role	567:574	the role of LXRs in fructose-induced ChREBP activation and lipogenesis	567:636	However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown.
28661453	3	15	theme	LXRs	579:582	arg1	unknown					651:657	unknown	651:657	unknown	651:657	However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown.
28661453	1	16	theme	Liver	104:108	arg1	LXRα/β					123:128	LXRα/β	123:128	LXRα/β	123:128	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	16	theme	Liver	104:108	arg1	receptors					112:120	Liver X receptors	104:120	Liver X receptors (LXRα/β)	104:129	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	16	theme	Liver	104:108	arg1	players					202:208	key players	198:208	key players in the transcriptional control of hepatic de novo lipogenesis	198:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	16	theme	Liver	104:108	arg1	proteins					173:180	carbohydrate response element-binding proteins	135:180	carbohydrate response element-binding proteins (ChREBPα/β)	135:192	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	4	17	theme	wild	857:860	arg1	h					854:854	12 h	851:854	12 h	851:854	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	17	theme	wild	857:860	arg1	type					862:865	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	type	862:865	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	6	18	theme	fed	1132:1134	arg1	glucose					1124:1130	glucose fed	1124:1134	glucose fed	1124:1134	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	4	19	theme	high	701:704	arg1	fructose					706:713	high fructose	701:713	high fructose	701:713	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	1	20	from	players	202:208	arg1	control					233:239	the transcriptional control	213:239	the transcriptional control of hepatic de novo lipogenesis	213:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	5	21	theme	fed	980:982	arg1	mice					992:995	glucose fed, but not fructose fed LXRα-/- mice	950:995	glucose fed, but not fructose fed LXRα-/- mice	950:995	Hepatic lipogenic gene expression was reduced in glucose fed, but not fructose fed LXRα-/- mice.
28661453	7	22	theme	LXRα-/-	1245:1251	arg1	mice					1253:1256	fructose fed LXRα-/- mice	1232:1256	fructose fed LXRα-/- mice	1232:1256	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	0	23	theme	Hepatic	15:21	arg1	Activity					31:38	Hepatic ChREBPα Activity	15:38	Hepatic ChREBPα Activity	15:38	LXRα Regulates Hepatic ChREBPα Activity and Lipogenesis upon Glucose, but Not Fructose Feeding in Mice.
28661453	2	24	theme	important	474:482	arg1	roles					484:488	important roles	474:488	important roles for LXRs in linking hepatic glucose utilization to lipid synthesis	474:555	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	6	25	from	activity	1112:1119	arg1	mice					1158:1161	glucose fed, but not fructose fed mice	1124:1161	glucose fed, but not fructose fed mice	1124:1161	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	7	26	with	concomitant	1259:1269	arg1	expression					1315:1324	increased glucose-6-phosphatase (G6pc) expression	1276:1324	increased glucose-6-phosphatase (G6pc) expression	1276:1324	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	7	26	with	concomitant	1259:1269	arg1	LXRβ					1348:1351	O-GlcNAc modified LXRβ	1330:1351	O-GlcNAc modified LXRβ	1330:1351	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	2	27	theme	hepatic	510:516	arg1	utilization					526:536	hepatic glucose utilization	510:536	hepatic glucose utilization	510:536	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	8	28	from	feeding	1572:1578	arg1	mice					1583:1586	mice	1583:1586	mice	1583:1586	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	0	29	theme	Fructose	78:85	arg1	Feeding					87:93	Fructose Feeding	78:93	Fructose Feeding in Mice	78:101	LXRα Regulates Hepatic ChREBPα Activity and Lipogenesis upon Glucose, but Not Fructose Feeding in Mice.
28661453	5	30	theme	Hepatic	901:907	arg1	expression					924:933	Hepatic lipogenic gene expression	901:933	Hepatic lipogenic gene expression	901:933	Hepatic lipogenic gene expression was reduced in glucose fed, but not fructose fed LXRα-/- mice.
28661453	4	31	theme	carbohydrate	750:761	arg1	metabolism					763:772	hepatic carbohydrate metabolism	742:772	hepatic carbohydrate metabolism	742:772	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	5	32	theme	gene	919:922	arg1	expression					924:933	Hepatic lipogenic gene expression	901:933	Hepatic lipogenic gene expression	901:933	Hepatic lipogenic gene expression was reduced in glucose fed, but not fructose fed LXRα-/- mice.
28661453	7	33	theme	fed	1241:1243	arg1	mice					1253:1256	fructose fed LXRα-/- mice	1232:1256	fructose fed LXRα-/- mice	1232:1256	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	2	34	theme	gene	436:439	arg1	expression					441:450	lipogenic gene expression	426:450	lipogenic gene expression	426:450	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	1	35	theme	de	252:253	arg1	lipogenesis					260:270	hepatic de novo lipogenesis	244:270	hepatic de novo lipogenesis	244:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	4	36	theme	glucose	723:729	arg1	feeding					731:737	high glucose feeding	718:737	high glucose feeding	718:737	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	3	37	from	role	571:574	arg1	lipogenesis					626:636	lipogenesis	626:636	lipogenesis	626:636	However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown.
28661453	3	37	from	role	571:574	arg1	activation					611:620	fructose-induced ChREBP activation	587:620	fructose-induced ChREBP activation	587:620	However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown.
28661453	4	38	dep	fasted	819:824	arg1	h					830:830	24 h	827:830	24 h	827:830	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	1	39	theme	lipogenesis	260:270	arg1	control					233:239	the transcriptional control	213:239	the transcriptional control of hepatic de novo lipogenesis	213:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	5	40	theme	fed	958:960	arg1	mice					992:995	glucose fed, but not fructose fed LXRα-/- mice	950:995	glucose fed, but not fructose fed LXRα-/- mice	950:995	Hepatic lipogenic gene expression was reduced in glucose fed, but not fructose fed LXRα-/- mice.
28661453	7	41	theme	L-pk	1201:1204	arg1	promoter					1206:1213	the L-pk promoter	1197:1213	the L-pk promoter	1197:1213	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	7	42	theme	fructose	1417:1424	arg1	feeding					1426:1432	fructose feeding	1417:1432	fructose feeding	1417:1432	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	6	43	theme	pyruvate-kinase	1049:1063	arg1	expression					1029:1038	lower expression	1023:1038	lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ	1023:1082	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	3	44	theme	fructose-induced	587:602	arg1	activation					611:620	fructose-induced ChREBP activation	587:620	fructose-induced ChREBP activation	587:620	However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown.
28661453	1	45	theme	key	198:200	arg1	receptors					112:120	Liver X receptors	104:120	Liver X receptors (LXRα/β)	104:129	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	45	theme	key	198:200	arg1	players					202:208	key players	198:208	key players in the transcriptional control of hepatic de novo lipogenesis	198:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	45	theme	key	198:200	arg1	proteins					173:180	carbohydrate response element-binding proteins	135:180	carbohydrate response element-binding proteins (ChREBPα/β)	135:192	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	7	46	theme	ChREBP	1179:1184	arg1	binding					1186:1192	ChREBP binding	1179:1192	ChREBP binding to the L-pk promoter	1179:1213	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	4	47	theme	gene	788:791	arg1	expression					793:802	lipogenic gene expression	778:802	lipogenic gene expression	778:802	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	2	48	theme	O-linked	353:360	arg1	O-GlcNAc					383:390	O-GlcNAc	383:390	O-GlcNAc	383:390	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	48	theme	O-linked	353:360	arg1	N-acetylglucosamine					362:380	feeding-induced nuclear O-linked N-acetylglucosamine	329:380	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	6	49	theme	lower	1023:1027	arg1	expression					1029:1038	lower expression	1023:1038	lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ	1023:1082	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	8	50	theme	lipogenesis	1508:1518	arg1	LXRα					1466:1469	LXRα	1466:1469	LXRα	1466:1469	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	8	50	theme	lipogenesis	1508:1518	arg1	regulator					1487:1495	an important regulator	1474:1495	an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose	1474:1552	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	2	51	theme	feeding-induced	329:343	arg1	O-GlcNAc					383:390	O-GlcNAc	383:390	O-GlcNAc	383:390	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	51	theme	feeding-induced	329:343	arg1	N-acetylglucosamine					362:380	feeding-induced nuclear O-linked N-acetylglucosamine	329:380	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	1	52	theme	transcriptional	217:231	arg1	control					233:239	the transcriptional control	213:239	the transcriptional control of hepatic de novo lipogenesis	213:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	8	53	theme	ChREBPα	1524:1530	arg1	activity					1532:1539	ChREBPα activity	1524:1539	ChREBPα activity	1524:1539	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	4	54	theme	fasted-refed	837:848	arg1	h					854:854	12 h	851:854	12 h	851:854	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	54	theme	fasted-refed	837:848	arg1	type					862:865	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	type	862:865	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	6	55	theme	reduced	1096:1102	arg1	activity					1112:1119	reduced ChREBPα activity	1096:1119	reduced ChREBPα activity in glucose fed, but not fructose fed mice	1096:1161	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	1	56	theme	carbohydrate	135:146	arg1	ChREBPα/β					183:191	ChREBPα/β	183:191	ChREBPα/β	183:191	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	56	theme	carbohydrate	135:146	arg1	proteins					173:180	carbohydrate response element-binding proteins	135:180	carbohydrate response element-binding proteins (ChREBPα/β)	135:192	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	56	theme	carbohydrate	135:146	arg1	players					202:208	key players	198:208	key players in the transcriptional control of hepatic de novo lipogenesis	198:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	56	theme	carbohydrate	135:146	arg1	receptors					112:120	Liver X receptors	104:120	Liver X receptors (LXRα/β)	104:129	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	4	57	theme	fasted	819:824	arg1	h					854:854	12 h	851:854	12 h	851:854	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	57	theme	fasted	819:824	arg1	type					862:865	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	type	862:865	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	7	58	theme	modified	1339:1346	arg1	LXRβ					1348:1351	O-GlcNAc modified LXRβ	1330:1351	O-GlcNAc modified LXRβ	1330:1351	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	1	59	theme	element-binding	157:171	arg1	ChREBPα/β					183:191	ChREBPα/β	183:191	ChREBPα/β	183:191	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	59	theme	element-binding	157:171	arg1	proteins					173:180	carbohydrate response element-binding proteins	135:180	carbohydrate response element-binding proteins (ChREBPα/β)	135:192	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	59	theme	element-binding	157:171	arg1	players					202:208	key players	198:208	key players in the transcriptional control of hepatic de novo lipogenesis	198:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	59	theme	element-binding	157:171	arg1	receptors					112:120	Liver X receptors	104:120	Liver X receptors (LXRα/β)	104:129	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	2	60	theme	double	280:285	arg1	mice					311:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	61	theme	glucose	518:524	arg1	utilization					526:536	hepatic glucose utilization	510:536	hepatic glucose utilization	510:536	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	8	62	theme	important	1477:1485	arg1	LXRα					1466:1469	LXRα	1466:1469	LXRα	1466:1469	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	8	62	theme	important	1477:1485	arg1	regulator					1487:1495	an important regulator	1474:1495	an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose	1474:1552	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	4	63	theme	LXRα-/-	886:892	arg1	mice					895:898	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	mice	895:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	64	from	type	862:865	arg1	metabolism					763:772	hepatic carbohydrate metabolism	742:772	hepatic carbohydrate metabolism	742:772	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	64	from	type	862:865	arg1	livers					807:812	livers	807:812	livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	807:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	64	from	type	862:865	arg1	expression					793:802	lipogenic gene expression	778:802	lipogenic gene expression	778:802	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	7	65	theme	increased	1276:1284	arg1	expression					1315:1324	increased glucose-6-phosphatase (G6pc) expression	1276:1324	increased glucose-6-phosphatase (G6pc) expression	1276:1324	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	3	66	theme	ChREBP	604:609	arg1	activation					611:620	fructose-induced ChREBP activation	587:620	fructose-induced ChREBP activation	587:620	However, the role of LXRs in fructose-induced ChREBP activation and lipogenesis is currently unknown.
28661453	4	67	from	expression	793:802	arg1	mice					895:898	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	mice	895:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	67	from	expression	793:802	arg1	livers					807:812	livers	807:812	livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	807:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	67	from	expression	793:802	arg1	h					854:854	12 h	851:854	12 h	851:854	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	67	from	expression	793:802	arg1	type					862:865	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	type	862:865	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	1	68	theme	X	110:110	arg1	LXRα/β					123:128	LXRα/β	123:128	LXRα/β	123:128	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	68	theme	X	110:110	arg1	receptors					112:120	Liver X receptors	104:120	Liver X receptors (LXRα/β)	104:129	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	68	theme	X	110:110	arg1	players					202:208	key players	198:208	key players in the transcriptional control of hepatic de novo lipogenesis	198:270	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	1	68	theme	X	110:110	arg1	proteins					173:180	carbohydrate response element-binding proteins	135:180	carbohydrate response element-binding proteins (ChREBPα/β)	135:192	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	0	69	from	Feeding	87:93	arg1	Mice					98:101	Mice	98:101	Mice	98:101	LXRα Regulates Hepatic ChREBPα Activity and Lipogenesis upon Glucose, but Not Fructose Feeding in Mice.
28661453	6	70	theme	glucose	1124:1130	arg1	mice					1158:1161	glucose fed, but not fructose fed mice	1124:1161	glucose fed, but not fructose fed mice	1124:1161	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	5	71	theme	LXRα-/-	984:990	arg1	mice					992:995	glucose fed, but not fructose fed LXRα-/- mice	950:995	glucose fed, but not fructose fed LXRα-/- mice	950:995	Hepatic lipogenic gene expression was reduced in glucose fed, but not fructose fed LXRα-/- mice.
28661453	4	72	from	metabolism	763:772	arg1	mice					895:898	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	mice	895:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	72	from	metabolism	763:772	arg1	livers					807:812	livers	807:812	livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	807:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	72	from	metabolism	763:772	arg1	h					854:854	12 h	851:854	12 h	851:854	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	72	from	metabolism	763:772	arg1	type					862:865	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	type	862:865	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	1	73	dep	de	252:253	arg1	novo					255:258	novo	255:258	novo	255:258	Liver X receptors (LXRα/β) and carbohydrate response element-binding proteins (ChREBPα/β) are key players in the transcriptional control of hepatic de novo lipogenesis.
28661453	2	74	contain	have	316:319	arg1	mice					311:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	74	contain	have	316:319	arg2	activity					412:419	ChREBPα activity	404:419	ChREBPα activity	404:419	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	74	contain	have	316:319	arg2	signaling					393:401	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	74	contain	have	316:319	arg2	expression					441:450	lipogenic gene expression	426:450	lipogenic gene expression	426:450	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	4	75	theme	feeding	731:737	arg1	effects					690:696	the effects	686:696	the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	686:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	5	76	theme	lipogenic	909:917	arg1	expression					924:933	Hepatic lipogenic gene expression	901:933	Hepatic lipogenic gene expression	901:933	Hepatic lipogenic gene expression was reduced in glucose fed, but not fructose fed LXRα-/- mice.
28661453	8	77	theme	fructose	1563:1570	arg1	feeding					1572:1578	fructose feeding	1563:1578	fructose feeding in mice	1563:1586	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	7	78	theme	fructose	1232:1239	arg1	mice					1253:1256	fructose fed LXRα-/- mice	1232:1256	fructose fed LXRα-/- mice	1232:1256	Interestingly, ChREBP binding to the L-pk promoter was increased in fructose fed LXRα-/- mice, concomitant with increased glucose-6-phosphatase (G6pc) expression and O-GlcNAc modified LXRβ, suggesting a role for LXRβ in regulating ChREBPα activity upon fructose feeding.
28661453	4	79	theme	hepatic	742:748	arg1	metabolism					763:772	hepatic carbohydrate metabolism	742:772	hepatic carbohydrate metabolism	742:772	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	2	80	theme	lipogenic	426:434	arg1	expression					441:450	lipogenic gene expression	426:450	lipogenic gene expression	426:450	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	4	81	theme	fructose	706:713	arg1	effects					690:696	the effects	686:696	the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	686:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	2	82	theme	N-acetylglucosamine	362:380	arg1	signaling					393:401	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	0	83	theme	ChREBPα	23:29	arg1	Activity					31:38	Hepatic ChREBPα Activity	15:38	Hepatic ChREBPα Activity	15:38	LXRα Regulates Hepatic ChREBPα Activity and Lipogenesis upon Glucose, but Not Fructose Feeding in Mice.
28661453	6	84	theme	fructose	1145:1152	arg1	mice					1158:1161	glucose fed, but not fructose fed mice	1124:1161	glucose fed, but not fructose fed mice	1124:1161	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	4	85	theme	high	718:721	arg1	feeding					731:737	high glucose feeding	718:737	high glucose feeding	718:737	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	2	86	theme	ChREBPα	404:410	arg1	activity					412:419	ChREBPα activity	404:419	ChREBPα activity	404:419	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	4	87	theme	LXRα	871:874	arg1	mice					895:898	fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice	819:898	mice	895:898	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	88	theme	lipogenic	778:786	arg1	expression					793:802	lipogenic gene expression	778:802	lipogenic gene expression	778:802	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	6	89	theme	liver	1043:1047	arg1	pyruvate-kinase					1049:1063	liver pyruvate-kinase	1043:1063	liver pyruvate-kinase (L-pk)	1043:1070	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	8	90	theme	hepatic	1500:1506	arg1	lipogenesis					1508:1518	hepatic lipogenesis	1500:1518	hepatic lipogenesis	1500:1518	In conclusion, we propose that LXRα is an important regulator of hepatic lipogenesis and ChREBPα activity upon glucose, but not fructose feeding in mice.
28661453	2	91	theme	LXRα-/-/β-/-	297:308	arg1	mice					311:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice	273:314	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	4	92	from	effects	690:696	arg1	metabolism					763:772	hepatic carbohydrate metabolism	742:772	hepatic carbohydrate metabolism	742:772	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	4	92	from	effects	690:696	arg1	expression					793:802	lipogenic gene expression	778:802	lipogenic gene expression	778:802	In this study, we studied the effects of high fructose or high glucose feeding on hepatic carbohydrate metabolism and lipogenic gene expression in livers from fasted (24 h) and fasted-refed (12 h) wild type and LXRα knockout (LXRα-/-) mice.
28661453	6	93	dep	pyruvate-kinase	1049:1063	arg1	L-pk					1066:1069	L-pk	1066:1069	L-pk	1066:1069	This was associated with lower expression of liver pyruvate-kinase (L-pk) and Chrebpβ, indicating reduced ChREBPα activity in glucose fed, but not fructose fed mice.
28661453	2	94	theme	nuclear	345:351	arg1	O-GlcNAc					383:390	O-GlcNAc	383:390	O-GlcNAc	383:390	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
28661453	2	94	theme	nuclear	345:351	arg1	N-acetylglucosamine					362:380	feeding-induced nuclear O-linked N-acetylglucosamine	329:380	reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling	321:401	LXRα/β double knockout (LXRα-/-/β-/-) mice have reduced feeding-induced nuclear O-linked N-acetylglucosamine (O-GlcNAc) signaling, ChREBPα activity, and lipogenic gene expression in livers, suggesting important roles for LXRs in linking hepatic glucose utilization to lipid synthesis.
31215094	6	0	theme	kappa	885:889	arg1	NF-κB					894:898	NF-κB	894:898	NF-κB	894:898	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	0	theme	kappa	885:889	arg1	p65					902:904	p65	902:904	p65	902:904	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	0	theme	kappa	885:889	arg1	B					891:891	nuclear factor kappa B	870:891	nuclear factor kappa B (NF-κB) (p65)	870:905	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	0	1	theme	biosynthetic	24:35	arg1	pathway					37:43	the hexosamine biosynthetic pathway	9:43	the hexosamine biosynthetic pathway	9:43	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	17	2	theme	NF-κB	2303:2307	arg1	activation					2315:2324	NF-κB (p65) activation	2303:2324	NF-κB (p65) activation	2303:2324	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	16	3	theme	phosphate	2152:2160	arg1	PPP					2171:2173	PPP	2171:2173	PPP	2171:2173	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	16	3	theme	phosphate	2152:2160	arg1	pathway					2162:2168	the pentose phosphate pathway	2140:2168	the pentose phosphate pathway (PPP)	2140:2174	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	6	4	theme	nuclear	870:876	arg1	NF-κB					894:898	NF-κB	894:898	NF-κB	894:898	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	4	theme	nuclear	870:876	arg1	p65					902:904	p65	902:904	p65	902:904	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	4	theme	nuclear	870:876	arg1	B					891:891	nuclear factor kappa B	870:891	nuclear factor kappa B (NF-κB) (p65)	870:905	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	17	5	theme	p65	2310:2312	arg1	activation					2315:2324	NF-κB (p65) activation	2303:2324	NF-κB (p65) activation	2303:2324	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	13	6	theme	cell	1747:1750	arg1	lines					1752:1756	cell lines	1747:1756	cell lines	1747:1756	Overall, glucose metabolism was upregulated in both esophageal cancer tissue and cell lines.
31215094	14	7	dep	trigger	1821:1827	arg1	facilitating					1902:1913	facilitating	1902:1913	inducing genetic mutations as well as facilitating carcinogenesis and cancer progression	1864:1951	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	14	7	dep	trigger	1821:1827	arg1	inducing					1864:1871	inducing	1864:1871	inducing genetic mutations as well as facilitating carcinogenesis and cancer progression	1864:1951	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	1	8	theme	reflux	249:254	arg1	models					241:246	rat duodenal contents reflux models	212:246	rat duodenal contents reflux models (reflux model)	212:261	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	8	theme	reflux	249:254	arg1	model					256:260	reflux model	249:260	reflux model	249:260	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	7	9	theme	pathway	1059:1065	arg1	activation					1073:1082	greater hexosamine biosynthesis pathway (HBP) activation	1027:1082	greater hexosamine biosynthesis pathway (HBP) activation	1027:1082	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	8	10	theme	transferase	1148:1158	arg1	Expression					1125:1134	Expression	1125:1134	Expression of O-GlcNAc transferase (OGT)	1125:1164	Expression of O-GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium.
31215094	13	11	theme	esophageal	1718:1727	arg1	tissue					1736:1741	esophageal cancer tissue	1718:1741	esophageal cancer tissue	1718:1741	Overall, glucose metabolism was upregulated in both esophageal cancer tissue and cell lines.
31215094	7	12	theme	hexosamine	1035:1044	arg1	HBP					1068:1070	HBP	1068:1070	HBP	1068:1070	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	7	12	theme	hexosamine	1035:1044	arg1	pathway					1059:1065	hexosamine biosynthesis pathway	1035:1065	greater hexosamine biosynthesis pathway (HBP) activation	1027:1082	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	3	13	theme	primary	538:544	arg1	ESCC					546:549	primary ESCC	538:549	primary ESCC	538:549	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	16	14	theme	cell	2083:2086	arg1	experiments					2099:2109	The cell line-based experiments	2079:2109	The cell line-based experiments	2079:2109	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	3	15	theme	nonmetastatic	523:535	arg1	ESCC					546:549	primary ESCC	538:549	primary ESCC	538:549	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	14	16	theme	p65	1835:1837	arg1	activation					1840:1849	NF-κB(p65) activation	1829:1849	NF-κB(p65) activation	1829:1849	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	10	17	from	overexpression	1408:1421	arg1	response					1426:1433	response	1426:1433	response to TCA exposure	1426:1449	G6PD overexpression in response to TCA exposure was observed.
31215094	8	18	theme	squamous	1238:1245	arg1	epithelium					1247:1256	nonneoplastic squamous epithelium	1224:1256	nonneoplastic squamous epithelium	1224:1256	Expression of O-GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium.
31215094	7	19	theme	reflux	1003:1008	arg1	models					1010:1015	the reflux models	999:1015	the reflux models	999:1015	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	14	20	theme	NF-κB	1829:1833	arg1	activation					1840:1849	NF-κB(p65) activation	1829:1849	NF-κB(p65) activation	1829:1849	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	1	21	theme	squamous	127:134	arg1	ESCCs					153:157	ESCCs	153:157	ESCCs	153:157	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	21	theme	squamous	127:134	arg1	carcinomas					141:150	Esophageal squamous cell carcinomas	116:150	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs)	116:192	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	4	22	theme	ESCC-DR	650:656	arg1	cells					658:662	ESCC-DR cells	650:662	ESCC-DR cells	650:662	ESCC-DRtca2M was prepared by treating ESCC-DR cells with taurocholic acid (TCA) to accelerate cancer progression.
31215094	0	23	theme	phosphate	57:65	arg1	pathway					67:73	pentose phosphate pathway	49:73	pentose phosphate pathway	49:73	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	12	24	theme	cells	1659:1663	arg1	excess					1641:1646	excess	1641:1646	excess of ESCC-DR cells	1641:1663	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	0	25	from	Roles	0:4	arg1	development					103:113	bile acid-induced cancer development	78:113	bile acid-induced cancer development	78:113	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	10	26	theme	G6PD	1403:1406	arg1	overexpression					1408:1421	G6PD overexpression	1403:1421	G6PD overexpression in response to TCA exposure	1403:1449	G6PD overexpression in response to TCA exposure was observed.
31215094	15	27	theme	esophageal	1997:2006	arg1	tissue					2015:2020	esophageal cancer tissue	1997:2020	esophageal cancer tissue	1997:2020	Glucose metabolism was upregulated in both esophageal cancer tissue and cell lines, and the HBP was activated in the former.
31215094	0	28	theme	acid-induced	83:94	arg1	development					103:113	bile acid-induced cancer development	78:113	bile acid-induced cancer development	78:113	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	9	29	theme	cell	1271:1274	arg1	experiments					1287:1297	cell line-based experiments	1271:1297	cell line-based experiments	1271:1297	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	12	30	theme	chromosomal	1612:1622	arg1	abnormalities					1624:1636	additional chromosomal abnormalities	1601:1636	additional chromosomal abnormalities in excess of ESCC-DR cells	1601:1663	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	6	31	theme	N-Acetylglucosamine	920:938	arg1	levels					818:823	protein expression levels	799:823	protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc)	799:949	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	16	32	theme	higher	2179:2184	arg1	degrees					2186:2192	higher degrees	2179:2192	higher degrees of malignancy	2179:2206	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	2	33	theme	cancer	357:362	arg1	onset					364:368	cancer onset	357:368	cancer onset	357:368	The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression.
31215094	9	34	theme	malignancy	1391:1400	arg1	degrees					1380:1386	higher degrees	1373:1386	higher degrees of malignancy	1373:1400	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	15	35	theme	cell	2026:2029	arg1	lines					2031:2035	cell lines	2026:2035	cell lines	2026:2035	Glucose metabolism was upregulated in both esophageal cancer tissue and cell lines, and the HBP was activated in the former.
31215094	3	36	theme	Metabolomics	387:398	arg1	analyses					400:407	Metabolomics analyses	387:407	Metabolomics analyses	387:407	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	12	37	theme	ESCC-DRtca2M	1578:1589	arg1	cells					1591:1595	ESCC-DRtca2M cells	1578:1595	ESCC-DRtca2M cells	1578:1595	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	4	38	theme	cancer	706:711	arg1	progression					713:723	cancer progression	706:723	cancer progression	706:723	ESCC-DRtca2M was prepared by treating ESCC-DR cells with taurocholic acid (TCA) to accelerate cancer progression.
31215094	14	39	theme	bile	1765:1768	arg1	acids					1770:1774	bile acids	1765:1774	bile acids	1765:1774	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	6	40	theme	dehydrogenase	848:860	arg1	levels					818:823	protein expression levels	799:823	protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc)	799:949	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	14	41	theme	cancer	1934:1939	arg1	progression					1941:1951	cancer progression	1934:1951	cancer progression	1934:1951	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	7	42	theme	nonneoplastic	1102:1114	arg1	tissues					1116:1122	the nonneoplastic tissues	1098:1122	the nonneoplastic tissues	1098:1122	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	9	43	from	degrees	1380:1386	arg1	activation					1320:1329	the greater activation	1308:1329	the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy	1308:1400	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	17	44	dep	trigger	2271:2277	arg1	inducing					2339:2346	inducing	2339:2346	inducing genetic mutations as well as facilitating carcinogenesis and cancer progression	2339:2426	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	17	44	dep	trigger	2271:2277	arg1	facilitating					2377:2388	facilitating	2377:2388	inducing genetic mutations as well as facilitating carcinogenesis and cancer progression	2339:2426	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	3	45	theme	thoracic	595:602	arg1	lesion					604:609	a metastatic thoracic lesion	582:609	a metastatic thoracic lesion	582:609	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	11	46	theme	other	1550:1554	arg1	lines					1561:1565	the other cell lines	1546:1565	the other cell lines	1546:1565	Both NF-κB (p65) and O-GlcNAc were expressed more highly in ESCC-DRtca2M than in the other cell lines.
31215094	3	47	theme	tissues	467:473	arg1	samples					427:433	samples	427:433	samples of neoplastic and nonneoplastic tissues from reflux models	427:492	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	5	48	theme	comprehensive	754:766	arg1	analyses					776:783	comprehensive genomic analyses	754:783	comprehensive genomic analyses	754:783	The lines were subjected to comprehensive genomic analyses.
31215094	9	49	theme	phosphate	1346:1354	arg1	PPP					1365:1367	PPP	1365:1367	PPP	1365:1367	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	9	49	theme	phosphate	1346:1354	arg1	pathway					1356:1362	the pentose phosphate pathway	1334:1362	the pentose phosphate pathway (PPP)	1334:1368	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	6	50	theme	expression	807:816	arg1	levels					818:823	protein expression levels	799:823	protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc)	799:949	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	17	51	theme	G6PD	2279:2282	arg1	overexpression					2284:2297	G6PD overexpression	2279:2297	G6PD overexpression	2279:2297	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	16	52	theme	pentose	2144:2150	arg1	PPP					2171:2173	PPP	2171:2173	PPP	2171:2173	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	16	52	theme	pentose	2144:2150	arg1	pathway					2162:2168	the pentose phosphate pathway	2140:2168	the pentose phosphate pathway (PPP)	2140:2174	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	2	53	theme	bile	328:331	arg1	stimulation					338:348	bile acid stimulation	328:348	bile acid stimulation	328:348	The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression.
31215094	1	54	theme	duodenal	216:223	arg1	models					241:246	rat duodenal contents reflux models	212:246	rat duodenal contents reflux models (reflux model)	212:261	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	54	theme	duodenal	216:223	arg1	model					256:260	reflux model	249:260	reflux model	249:260	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	6	55	theme	B	891:891	arg1	levels					818:823	protein expression levels	799:823	protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc)	799:949	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	14	56	theme	genetic	1873:1879	arg1	mutations					1881:1889	genetic mutations	1873:1889	genetic mutations	1873:1889	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	16	57	theme	pathway	2162:2168	arg1	upregulation					2124:2135	upregulation	2124:2135	upregulation of the pentose phosphate pathway (PPP)	2124:2174	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	12	58	contain	had	1597:1599	arg1	cells					1591:1595	ESCC-DRtca2M cells	1578:1595	ESCC-DRtca2M cells	1578:1595	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	12	58	contain	had	1597:1599	arg2	abnormalities					1624:1636	additional chromosomal abnormalities	1601:1636	additional chromosomal abnormalities in excess of ESCC-DR cells	1601:1663	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	3	59	theme	reflux	480:485	arg1	models					487:492	reflux models	480:492	reflux models	480:492	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	1	60	theme	reflux	234:239	arg1	models					241:246	rat duodenal contents reflux models	212:246	rat duodenal contents reflux models (reflux model)	212:261	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	60	theme	reflux	234:239	arg1	model					256:260	reflux model	249:260	reflux model	249:260	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	6	61	theme	factor	878:883	arg1	NF-κB					894:898	NF-κB	894:898	NF-κB	894:898	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	61	theme	factor	878:883	arg1	p65					902:904	p65	902:904	p65	902:904	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	61	theme	factor	878:883	arg1	B					891:891	nuclear factor kappa B	870:891	nuclear factor kappa B (NF-κB) (p65)	870:905	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	3	62	from	models	487:492	arg1	tissues					467:473	neoplastic and nonneoplastic tissues	438:473	tissues	467:473	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	3	62	from	models	487:492	arg1	samples					427:433	samples	427:433	samples of neoplastic and nonneoplastic tissues from reflux models	427:492	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	3	63	from	samples	427:433	arg1	models					487:492	reflux models	480:492	reflux models	480:492	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	12	64	from	abnormalities	1624:1636	arg1	excess					1641:1646	excess	1641:1646	excess of ESCC-DR cells	1641:1663	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	7	65	theme	biosynthesis	1046:1057	arg1	HBP					1068:1070	HBP	1068:1070	HBP	1068:1070	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	7	65	theme	biosynthesis	1046:1057	arg1	pathway					1059:1065	hexosamine biosynthesis pathway	1035:1065	greater hexosamine biosynthesis pathway (HBP) activation	1027:1082	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	3	66	dep	ESCC	546:549	arg1	a					521:521	a	521:521	a	521:521	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	7	67	theme	greater	1027:1033	arg1	activation					1073:1082	greater hexosamine biosynthesis pathway (HBP) activation	1027:1082	greater hexosamine biosynthesis pathway (HBP) activation	1027:1082	Cancers developed in the reflux models exhibited greater hexosamine biosynthesis pathway (HBP) activation compared with the nonneoplastic tissues.
31215094	8	68	theme	O-GlcNAc	1139:1146	arg1	OGT					1161:1163	OGT	1161:1163	OGT	1161:1163	Expression of O-GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium.
31215094	8	68	theme	O-GlcNAc	1139:1146	arg1	transferase					1148:1158	O-GlcNAc transferase	1139:1158	O-GlcNAc transferase (OGT)	1139:1164	Expression of O-GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium.
31215094	6	69	theme	O-linked	911:918	arg1	O-GlcNAc					941:948	O-GlcNAc	941:948	O-GlcNAc	941:948	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	69	theme	O-linked	911:918	arg1	N-Acetylglucosamine					920:938	O-linked N-Acetylglucosamine	911:938	O-linked N-Acetylglucosamine (O-GlcNAc)	911:949	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	17	70	theme	cancer	2409:2414	arg1	progression					2416:2426	cancer progression	2409:2426	cancer progression	2409:2426	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	13	71	theme	cancer	1729:1734	arg1	tissue					1736:1741	esophageal cancer tissue	1718:1741	esophageal cancer tissue	1718:1741	Overall, glucose metabolism was upregulated in both esophageal cancer tissue and cell lines.
31215094	16	72	theme	line-based	2088:2097	arg1	experiments					2099:2109	The cell line-based experiments	2079:2109	The cell line-based experiments	2079:2109	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	8	73	theme	nonneoplastic	1224:1236	arg1	epithelium					1247:1256	nonneoplastic squamous epithelium	1224:1256	nonneoplastic squamous epithelium	1224:1256	Expression of O-GlcNAc transferase (OGT) increased considerably in both ESCC and EAC compared with nonneoplastic squamous epithelium.
31215094	6	74	link	O-linked	911:918	arg1	O-GlcNAc					941:948	O-GlcNAc	941:948	O-GlcNAc	941:948	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	74	link	O-linked	911:918	arg1	N-Acetylglucosamine					920:938	O-linked N-Acetylglucosamine	911:938	O-linked N-Acetylglucosamine (O-GlcNAc)	911:949	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	1	75	theme	Esophageal	116:125	arg1	ESCCs					153:157	ESCCs	153:157	ESCCs	153:157	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	75	theme	Esophageal	116:125	arg1	carcinomas					141:150	Esophageal squamous cell carcinomas	116:150	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs)	116:192	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	17	76	theme	chronic	2245:2251	arg1	exposure					2253:2260	chronic exposure	2245:2260	chronic exposure	2245:2260	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	4	77	theme	taurocholic	669:679	arg1	acid					681:684	taurocholic acid	669:684	taurocholic acid (TCA) to accelerate cancer progression	669:723	ESCC-DRtca2M was prepared by treating ESCC-DR cells with taurocholic acid (TCA) to accelerate cancer progression.
31215094	4	77	theme	taurocholic	669:679	arg1	TCA					687:689	TCA	687:689	TCA	687:689	ESCC-DRtca2M was prepared by treating ESCC-DR cells with taurocholic acid (TCA) to accelerate cancer progression.
31215094	1	78	theme	cell	136:139	arg1	ESCCs					153:157	ESCCs	153:157	ESCCs	153:157	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	78	theme	cell	136:139	arg1	carcinomas					141:150	Esophageal squamous cell carcinomas	116:150	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs)	116:192	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	0	79	theme	pathway	67:73	arg1	Roles					0:4	Roles	0:4	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development	0:113	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	12	80	theme	ESCC-DR	1651:1657	arg1	cells					1659:1663	ESCC-DR cells	1651:1663	ESCC-DR cells	1651:1663	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	14	81	theme	chronic	1795:1801	arg1	exposure					1803:1810	chronic exposure	1795:1810	chronic exposure	1795:1810	While bile acids are not mutagenic, chronic exposure seems to trigger NF-κB(p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	0	82	theme	bile	78:81	arg1	development					103:113	bile acid-induced cancer development	78:113	bile acid-induced cancer development	78:113	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	0	83	theme	cancer	96:101	arg1	development					103:113	bile acid-induced cancer development	78:113	bile acid-induced cancer development	78:113	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	2	84	theme	present	268:274	arg1	study					276:280	The present study	264:280	The present study	264:280	The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression.
31215094	13	85	theme	glucose	1675:1681	arg1	metabolism					1683:1692	glucose metabolism	1675:1692	glucose metabolism	1675:1692	Overall, glucose metabolism was upregulated in both esophageal cancer tissue and cell lines.
31215094	9	86	theme	line-based	1276:1285	arg1	experiments					1287:1297	cell line-based experiments	1271:1297	cell line-based experiments	1271:1297	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	12	87	theme	additional	1601:1610	arg1	abnormalities					1624:1636	additional chromosomal abnormalities	1601:1636	additional chromosomal abnormalities in excess of ESCC-DR cells	1601:1663	Moreover, ESCC-DRtca2M cells had additional chromosomal abnormalities in excess of ESCC-DR cells.
31215094	17	88	theme	bile	2215:2218	arg1	acids					2220:2224	bile acids	2215:2224	bile acids	2215:2224	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	10	89	theme	TCA	1438:1440	arg1	exposure					1442:1449	TCA exposure	1438:1449	TCA exposure	1438:1449	G6PD overexpression in response to TCA exposure was observed.
31215094	16	90	theme	malignancy	2197:2206	arg1	degrees					2186:2192	higher degrees	2179:2192	higher degrees of malignancy	2179:2206	The cell line-based experiments demonstrated upregulation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	5	91	theme	genomic	768:774	arg1	analyses					776:783	comprehensive genomic analyses	754:783	comprehensive genomic analyses	754:783	The lines were subjected to comprehensive genomic analyses.
31215094	15	92	theme	cancer	2008:2013	arg1	tissue					2015:2020	esophageal cancer tissue	1997:2020	esophageal cancer tissue	1997:2020	Glucose metabolism was upregulated in both esophageal cancer tissue and cell lines, and the HBP was activated in the former.
31215094	2	93	theme	acid	333:336	arg1	stimulation					338:348	bile acid stimulation	328:348	bile acid stimulation	328:348	The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression.
31215094	0	94	theme	hexosamine	13:22	arg1	pathway					37:43	the hexosamine biosynthetic pathway	9:43	the hexosamine biosynthetic pathway	9:43	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	9	95	theme	greater	1312:1318	arg1	activation					1320:1329	the greater activation	1308:1329	the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy	1308:1400	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	3	96	theme	neoplastic	438:447	arg1	tissues					467:473	neoplastic and nonneoplastic tissues	438:473	tissues	467:473	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	0	97	theme	pathway	37:43	arg1	Roles					0:4	Roles	0:4	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development	0:113	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	6	98	theme	glucose-6-phosphate	828:846	arg1	G6PD					863:866	G6PD	863:866	G6PD	863:866	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	6	98	theme	glucose-6-phosphate	828:846	arg1	dehydrogenase					848:860	glucose-6-phosphate dehydrogenase	828:860	glucose-6-phosphate dehydrogenase (G6PD)	828:867	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	17	99	theme	genetic	2348:2354	arg1	mutations					2356:2364	genetic mutations	2348:2364	genetic mutations	2348:2364	While bile acids are not mutagenic, chronic exposure seems to trigger G6PD overexpression and NF-κB (p65) activation, potentially inducing genetic mutations as well as facilitating carcinogenesis and cancer progression.
31215094	3	100	theme	metastatic	584:593	arg1	lesion					604:609	a metastatic thoracic lesion	582:609	a metastatic thoracic lesion	582:609	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	9	101	theme	higher	1373:1378	arg1	degrees					1380:1386	higher degrees	1373:1386	higher degrees of malignancy	1373:1400	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	0	102	theme	pentose	49:55	arg1	pathway					67:73	pentose phosphate pathway	49:73	pentose phosphate pathway	49:73	Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.
31215094	9	103	theme	pentose	1338:1344	arg1	PPP					1365:1367	PPP	1365:1367	PPP	1365:1367	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	9	103	theme	pentose	1338:1344	arg1	pathway					1356:1362	the pentose phosphate pathway	1334:1362	the pentose phosphate pathway (PPP)	1334:1368	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	15	104	theme	Glucose	1954:1960	arg1	metabolism					1962:1971	Glucose metabolism	1954:1971	Glucose metabolism	1954:1971	Glucose metabolism was upregulated in both esophageal cancer tissue and cell lines, and the HBP was activated in the former.
31215094	9	105	theme	pathway	1356:1362	arg1	activation					1320:1329	the greater activation	1308:1329	the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy	1308:1400	Conversely, cell line-based experiments revealed the greater activation of the pentose phosphate pathway (PPP) at higher degrees of malignancy.
31215094	6	106	theme	protein	799:805	arg1	levels					818:823	protein expression levels	799:823	protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc)	799:949	In addition, protein expression levels of glucose-6-phosphate dehydrogenase (G6PD), nuclear factor kappa B (NF-κB) (p65) and O-linked N-Acetylglucosamine (O-GlcNAc) were compared among lines.
31215094	3	107	theme	nonneoplastic	453:465	arg1	tissues					467:473	neoplastic and nonneoplastic tissues	438:473	tissues	467:473	Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.
31215094	1	108	theme	rat	212:214	arg1	models					241:246	rat duodenal contents reflux models	212:246	rat duodenal contents reflux models (reflux model)	212:261	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	108	theme	rat	212:214	arg1	model					256:260	reflux model	249:260	reflux model	249:260	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	11	109	theme	cell	1556:1559	arg1	lines					1561:1565	the other cell lines	1546:1565	the other cell lines	1546:1565	Both NF-κB (p65) and O-GlcNAc were expressed more highly in ESCC-DRtca2M than in the other cell lines.
31215094	1	110	theme	contents	225:232	arg1	models					241:246	rat duodenal contents reflux models	212:246	rat duodenal contents reflux models (reflux model)	212:261	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
31215094	1	110	theme	contents	225:232	arg1	model					256:260	reflux model	249:260	reflux model	249:260	Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model).
29769320	7	0	theme	levels	1159:1164	arg1	Investigation					1076:1088	Investigation	1076:1088	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting	1076:1184	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	9	1	theme	embryonic	1808:1816	arg1	cells					1823:1827	human embryonic stem cells	1802:1827	human embryonic stem cells	1802:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	3	2	theme	missense	485:492	arg1	mutations					494:502	Three missense mutations	479:502	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT	479:548	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	3	from	mutations	494:502	arg1	repeats					535:541	the tetratricopeptide (TPR) repeats	507:541	the tetratricopeptide (TPR) repeats of OGT	507:548	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	3	from	mutations	494:502	arg1	TPR					530:532	TPR	530:532	TPR	530:532	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	4	theme	tetratricopeptide	511:527	arg1	repeats					535:541	the tetratricopeptide (TPR) repeats	507:541	the tetratricopeptide (TPR) repeats of OGT	507:548	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	4	theme	tetratricopeptide	511:527	arg1	TPR					530:532	TPR	530:532	TPR	530:532	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	9	5	theme	OGT	1615:1617	arg1	regions					1604:1610	the TPR regions	1596:1610	the TPR regions of OGT	1596:1617	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	0	6	link	X-linked	50:57	arg1	disability					72:81	X-linked intellectual disability	50:81	X-linked intellectual disability	50:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	9	7	from	profiles	1790:1797	arg1	cells					1823:1827	human embryonic stem cells	1802:1827	human embryonic stem cells	1802:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	3	8	theme	OGT	546:548	arg1	repeats					535:541	the tetratricopeptide (TPR) repeats	507:541	the tetratricopeptide (TPR) repeats of OGT	507:548	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	8	theme	OGT	546:548	arg1	TPR					530:532	TPR	530:532	TPR	530:532	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	7	9	from	changes	1202:1208	arg1	levels					1226:1231	steady-state levels	1213:1231	steady-state levels	1213:1231	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	7	9	from	changes	1202:1208	arg1	lines					1251:1255	the engineered lines	1236:1255	the engineered lines	1236:1255	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	1	10	theme	population	191:200	arg1	population					191:200	the world's population	179:200	the world's population	179:200	It is estimated that ∼1% of the world's population has intellectual disability, with males affected more often than females.
29769320	1	10	theme	population	191:200	arg1	%					174:174	∼1%	172:174	∼1% of the world's population	172:200	It is estimated that ∼1% of the world's population has intellectual disability, with males affected more often than females.
29769320	2	11	link	X-linked	286:293	arg1	OGT					276:278	OGT	276:278	OGT	276:278	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	2	11	link	X-linked	286:293	arg1	gene					295:298	an X-linked gene	283:298	an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates	283:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	9	12	theme	common	1731:1736	arg1	mechanism					1752:1760	a common, unelucidated mechanism	1729:1760	a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells	1729:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	1	13	theme	intellectual	206:217	arg1	disability					219:228	intellectual disability	206:228	intellectual disability	206:228	It is estimated that ∼1% of the world's population has intellectual disability, with males affected more often than females.
29769320	4	14	theme	additional	665:674	arg1	p.A259T					713:719	p.A259T	713:719	p.A259T	713:719	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	14	theme	additional	665:674	arg1	mutations					691:699	two additional novel missense mutations	661:699	two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families	661:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	14	theme	additional	665:674	arg1	G>A					708:710	c.775 G>A	702:710	c.775 G>A	702:710	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	14	theme	additional	665:674	arg1	c.1016					726:731	c.1016	726:731	c.1016	726:731	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	5	15	theme	variants	968:975	arg1	activities					950:959	activities	950:959	activities of the variants	950:975	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	8	16	theme	cell	1402:1405	arg1	determination					1412:1424	cell fate determination	1402:1424	cell fate determination	1402:1424	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	4	17	theme	missense	682:689	arg1	p.A259T					713:719	p.A259T	713:719	p.A259T	713:719	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	17	theme	missense	682:689	arg1	mutations					691:699	two additional novel missense mutations	661:699	two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families	661:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	17	theme	missense	682:689	arg1	G>A					708:710	c.775 G>A	702:710	c.775 G>A	702:710	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	17	theme	missense	682:689	arg1	c.1016					726:731	c.1016	726:731	c.1016	726:731	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	3	18	theme	intellectual	596:607	arg1	XLID					621:624	XLID	621:624	XLID	621:624	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	18	theme	intellectual	596:607	arg1	disability					609:618	X-linked intellectual disability	587:618	X-linked intellectual disability (XLID)	587:625	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	4	19	dep	mutations	691:699	arg1	p.A259T					713:719	p.A259T	713:719	p.A259T	713:719	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	19	dep	mutations	691:699	arg1	c.1016					726:731	c.1016	726:731	c.1016	726:731	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	19	dep	mutations	691:699	arg1	G>A					708:710	c.775 G>A	702:710	c.775 G>A	702:710	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	19	dep	mutations	691:699	arg1	mutations					691:699	two additional novel missense mutations	661:699	two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families	661:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	7	20	theme	hydrolase	1149:1157	arg1	levels					1159:1164	OGT and O-GlcNAc hydrolase levels	1132:1164	the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels	1093:1164	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	2	21	theme	intracellular	453:465	arg1	substrates					467:476	its intracellular substrates	449:476	its intracellular substrates	449:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	8	22	theme	liver	1430:1434	arg1	receptor					1458:1465	liver X receptor/retinoid X receptor	1430:1465	liver X receptor/retinoid X receptor signaling	1430:1475	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	9	23	theme	active	1699:1704	arg1	variants					1710:1717	the relatively stable and active TPR variants	1673:1717	the relatively stable and active TPR variants	1673:1717	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	8	24	theme	receptor/retinoid	1438:1454	arg1	receptor					1458:1465	liver X receptor/retinoid X receptor	1430:1465	liver X receptor/retinoid X receptor signaling	1430:1475	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	5	25	theme	OGT	883:885	arg1	variants					871:878	these XLID missense variants	851:878	these XLID missense variants of OGT	851:885	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	8	26	theme	receptor	1458:1465	arg1	signaling					1467:1475	liver X receptor/retinoid X receptor signaling	1430:1475	liver X receptor/retinoid X receptor signaling	1430:1475	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	0	27	theme	fate	117:120	arg1	determination					122:134	cell fate determination	112:134	cell fate determination	112:134	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	8	28	theme	differential	1283:1294	arg1	transcriptomes					1296:1309	the differential transcriptomes	1279:1309	the differential transcriptomes of the OGT variant-expressing stem cells	1279:1350	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	0	29	theme	O-GlcNAc	0:7	arg1	mutations					30:38	O-GlcNAc transferase missense mutations	0:38	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability	0:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	5	30	theme	XLID	857:860	arg1	variants					871:878	these XLID missense variants	851:878	these XLID missense variants of OGT	851:885	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	7	31	theme	engineered	1240:1249	arg1	lines					1251:1255	the engineered lines	1236:1255	the engineered lines	1236:1255	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	3	32	link	X-linked	587:594	arg1	XLID					621:624	XLID	621:624	XLID	621:624	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	32	link	X-linked	587:594	arg1	disability					609:618	X-linked intellectual disability	587:618	X-linked intellectual disability (XLID)	587:625	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	0	33	theme	missense	21:28	arg1	mutations					30:38	O-GlcNAc transferase missense mutations	0:38	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability	0:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	5	34	theme	variants	871:878	arg1	variants					871:878	these XLID missense variants	851:878	these XLID missense variants of OGT	851:885	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	5	34	theme	variants	871:878	arg1	five					843:846	five	843:846	five	843:846	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	7	35	theme	O-GlcNAc	1104:1111	arg1	profile					1113:1119	the global O-GlcNAc profile	1093:1119	the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels	1093:1164	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	8	36	theme	OGT	1318:1320	arg1	cells					1346:1350	the OGT variant-expressing stem cells	1314:1350	the OGT variant-expressing stem cells	1314:1350	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	2	37	theme	reversible	374:383	arg1	addition					385:392	the reversible addition	370:392	the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates	370:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	7	38	theme	steady-state	1213:1224	arg1	levels					1226:1231	steady-state levels	1213:1231	steady-state levels	1213:1231	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	2	39	theme	Ser/Thr	429:435	arg1	substrates					467:476	its intracellular substrates	449:476	its intracellular substrates	449:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	2	39	theme	Ser/Thr	429:435	arg1	residues					437:444	Ser/Thr residues	429:444	Ser/Thr residues of its intracellular substrates	429:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	8	40	theme	neuronal	1507:1514	arg1	development					1516:1526	neuronal development	1507:1526	neuronal development	1507:1526	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	8	41	theme	stem	1341:1344	arg1	cells					1346:1350	the OGT variant-expressing stem cells	1314:1350	the OGT variant-expressing stem cells	1314:1350	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	2	42	theme	O-GlcNAc	324:331	arg1	OGT					346:348	OGT	346:348	OGT	346:348	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	2	42	theme	O-GlcNAc	324:331	arg1	transferase					333:343	the enzyme O-GlcNAc transferase	313:343	the enzyme O-GlcNAc transferase (OGT)	313:349	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	0	43	theme	X-linked	50:57	arg1	disability					72:81	X-linked intellectual disability	50:81	X-linked intellectual disability	50:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	6	44	theme	cell	1047:1050	arg1	line					1052:1055	a male human embryonic stem cell line	1019:1055	a male human embryonic stem cell line using CRISPR/Cas9	1019:1073	We engineered each of the mutations into a male human embryonic stem cell line using CRISPR/Cas9.
29769320	9	45	theme	gene	1774:1777	arg1	profiles					1790:1797	gene expression profiles	1774:1797	gene expression profiles in human embryonic stem cells	1774:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	1	46	contain	has	202:204	arg2	disability					219:228	intellectual disability	206:228	intellectual disability	206:228	It is estimated that ∼1% of the world's population has intellectual disability, with males affected more often than females.
29769320	1	46	contain	has	202:204	arg1	%					174:174	∼1%	172:174	∼1% of the world's population	172:200	It is estimated that ∼1% of the world's population has intellectual disability, with males affected more often than females.
29769320	1	46	contain	has	202:204	arg1	population					191:200	the world's population	179:200	the world's population	179:200	It is estimated that ∼1% of the world's population has intellectual disability, with males affected more often than females.
29769320	4	47	theme	A>G	733:735	arg1	mutations					691:699	two additional novel missense mutations	661:699	two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families	661:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	47	theme	A>G	733:735	arg1	G>A					708:710	c.775 G>A	702:710	c.775 G>A	702:710	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	9	48	theme	additional	1554:1563	arg1	mutations					1565:1573	two additional mutations	1550:1573	two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells	1550:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	6	49	theme	embryonic	1032:1040	arg1	line					1052:1055	a male human embryonic stem cell line	1019:1055	a male human embryonic stem cell line using CRISPR/Cas9	1019:1073	We engineered each of the mutations into a male human embryonic stem cell line using CRISPR/Cas9.
29769320	6	50	theme	male	1021:1024	arg1	line					1052:1055	a male human embryonic stem cell line	1019:1055	a male human embryonic stem cell line using CRISPR/Cas9	1019:1073	We engineered each of the mutations into a male human embryonic stem cell line using CRISPR/Cas9.
29769320	9	51	theme	human	1802:1806	arg1	cells					1823:1827	human embryonic stem cells	1802:1827	human embryonic stem cells	1802:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	9	52	theme	stable	1688:1693	arg1	variants					1710:1717	the relatively stable and active TPR variants	1673:1717	the relatively stable and active TPR variants	1673:1717	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	9	53	dep	common	1731:1736	arg1	unelucidated					1739:1750	unelucidated	1739:1750	unelucidated	1739:1750	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	4	54	from	discovery	648:656	arg1	OGT					768:770	OGT	768:770	OGT	768:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	54	from	discovery	648:656	arg1	domain					758:763	the TPR domain	750:763	the TPR domain of OGT	750:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	9	55	theme	stem	1818:1821	arg1	cells					1823:1827	human embryonic stem cells	1802:1827	human embryonic stem cells	1802:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	4	56	theme	TPR	754:756	arg1	OGT					768:770	OGT	768:770	OGT	768:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	56	theme	TPR	754:756	arg1	domain					758:763	the TPR domain	750:763	the TPR domain of OGT	750:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	9	57	theme	TPR	1600:1602	arg1	regions					1604:1610	the TPR regions	1596:1610	the TPR regions of OGT	1596:1617	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	0	58	attach	linked	40:45	arg1	disability					72:81	X-linked intellectual disability	50:81	X-linked intellectual disability	50:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	0	58	attach	linked	40:45	arg2	mutations					30:38	O-GlcNAc transferase missense mutations	0:38	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability	0:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	4	59	dep	A>G	733:735	arg1	p.E339G					738:744	p.E339G	738:744	p.E339G	738:744	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	60	theme	OGT	768:770	arg1	OGT					768:770	OGT	768:770	OGT	768:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	60	theme	OGT	768:770	arg1	domain					758:763	the TPR domain	750:763	the TPR domain of OGT	750:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	2	61	theme	X-linked	286:293	arg1	OGT					276:278	OGT	276:278	OGT	276:278	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	2	61	theme	X-linked	286:293	arg1	gene					295:298	an X-linked gene	283:298	an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates	283:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	8	62	theme	genes	1384:1388	arg1	deregulation					1368:1379	shared deregulation	1361:1379	shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development	1361:1526	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	9	63	from	residues	1584:1591	arg1	regions					1604:1610	the TPR regions	1596:1610	the TPR regions of OGT	1596:1617	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	4	64	theme	affected	800:807	arg1	families					809:816	affected families	800:816	affected families	800:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	8	65	theme	fate	1407:1410	arg1	determination					1412:1424	cell fate determination	1402:1424	cell fate determination	1402:1424	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	5	66	dep	modest	900:905	arg1	declines					907:914	declines	907:914	declines in thermodynamic stability and/or activities of the variants	907:975	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	3	67	theme	X-linked	587:594	arg1	XLID					621:624	XLID	621:624	XLID	621:624	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	3	67	theme	X-linked	587:594	arg1	disability					609:618	X-linked intellectual disability	587:618	X-linked intellectual disability (XLID)	587:625	Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked intellectual disability (XLID).
29769320	5	68	theme	five	843:846	arg1	Characterization					819:834	Characterization	819:834	Characterization of all five of these XLID missense variants of OGT	819:885	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	4	69	theme	novel	676:680	arg1	p.A259T					713:719	p.A259T	713:719	p.A259T	713:719	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	69	theme	novel	676:680	arg1	mutations					691:699	two additional novel missense mutations	661:699	two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families	661:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	69	theme	novel	676:680	arg1	G>A					708:710	c.775 G>A	702:710	c.775 G>A	702:710	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	69	theme	novel	676:680	arg1	c.1016					726:731	c.1016	726:731	c.1016	726:731	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	7	70	theme	O-GlcNAc	1140:1147	arg1	levels					1159:1164	OGT and O-GlcNAc hydrolase levels	1132:1164	the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels	1093:1164	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	2	71	theme	substrates	467:476	arg1	substrates					467:476	its intracellular substrates	449:476	its intracellular substrates	449:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	2	71	theme	substrates	467:476	arg1	residues					437:444	Ser/Thr residues	429:444	Ser/Thr residues of its intracellular substrates	429:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	8	72	theme	X	1436:1436	arg1	receptor					1458:1465	liver X receptor/retinoid X receptor	1430:1465	liver X receptor/retinoid X receptor signaling	1430:1475	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	7	73	theme	OGT	1132:1134	arg1	levels					1159:1164	OGT and O-GlcNAc hydrolase levels	1132:1164	the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels	1093:1164	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	4	74	from	XLID	792:795	arg1	families					809:816	affected families	800:816	affected families	800:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	8	75	theme	X	1456:1456	arg1	receptor					1458:1465	liver X receptor/retinoid X receptor	1430:1465	liver X receptor/retinoid X receptor signaling	1430:1475	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	0	76	theme	cell	112:115	arg1	determination					122:134	cell fate determination	112:134	cell fate determination	112:134	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	9	77	theme	TPR	1706:1708	arg1	variants					1710:1717	the relatively stable and active TPR variants	1673:1717	the relatively stable and active TPR variants	1673:1717	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	7	78	theme	profile	1113:1119	arg1	Investigation					1076:1088	Investigation	1076:1088	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting	1076:1184	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	0	79	theme	transferase	9:19	arg1	mutations					30:38	O-GlcNAc transferase missense mutations	0:38	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability	0:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	4	80	from	domain	758:763	arg1	discovery					648:656	the discovery	644:656	the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families	644:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	81	theme	mutations	691:699	arg1	discovery					648:656	the discovery	644:656	the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families	644:816	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	82	from	mutations	691:699	arg1	OGT					768:770	OGT	768:770	OGT	768:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	4	82	from	mutations	691:699	arg1	domain					758:763	the TPR domain	750:763	the TPR domain of OGT	750:770	Here, we report the discovery of two additional novel missense mutations (c.775 G>A, p.A259T, and c.1016 A>G, p.E339G) in the TPR domain of OGT that segregate with XLID in affected families.
29769320	5	83	theme	missense	862:869	arg1	variants					871:878	these XLID missense variants	851:878	these XLID missense variants of OGT	851:885	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	2	84	theme	N-acetylglucosamine	397:415	arg1	addition					385:392	the reversible addition	370:392	the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates	370:476	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	8	85	theme	transcriptomes	1296:1309	arg1	analyses					1267:1274	analyses	1267:1274	analyses of the differential transcriptomes of the OGT variant-expressing stem cells	1267:1350	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	6	86	theme	human	1026:1030	arg1	line					1052:1055	a male human embryonic stem cell line	1019:1055	a male human embryonic stem cell line using CRISPR/Cas9	1019:1073	We engineered each of the mutations into a male human embryonic stem cell line using CRISPR/Cas9.
29769320	0	87	theme	intellectual	59:70	arg1	disability					72:81	X-linked intellectual disability	50:81	X-linked intellectual disability	50:81	O-GlcNAc transferase missense mutations linked to X-linked intellectual disability deregulate genes involved in cell fate determination and signaling.
29769320	7	88	theme	gross	1196:1200	arg1	changes					1202:1208	no gross changes	1193:1208	no gross changes in steady-state levels in the engineered lines	1193:1255	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	8	89	theme	variant-expressing	1322:1339	arg1	cells					1346:1350	the OGT variant-expressing stem cells	1314:1350	the OGT variant-expressing stem cells	1314:1350	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	2	90	theme	enzyme	317:322	arg1	OGT					346:348	OGT	346:348	OGT	346:348	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	2	90	theme	enzyme	317:322	arg1	transferase					333:343	the enzyme O-GlcNAc transferase	313:343	the enzyme O-GlcNAc transferase (OGT)	313:349	OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates.
29769320	6	91	theme	stem	1042:1045	arg1	line					1052:1055	a male human embryonic stem cell line	1019:1055	a male human embryonic stem cell line using CRISPR/Cas9	1019:1073	We engineered each of the mutations into a male human embryonic stem cell line using CRISPR/Cas9.
29769320	9	92	theme	expression	1779:1788	arg1	profiles					1790:1797	gene expression profiles	1774:1797	gene expression profiles in human embryonic stem cells	1774:1827	Thus, here we reveal two additional mutations encoding residues in the TPR regions of OGT that appear causal for XLID and provide evidence that the relatively stable and active TPR variants may share a common, unelucidated mechanism of altering gene expression profiles in human embryonic stem cells.
29769320	8	93	theme	cells	1346:1350	arg1	transcriptomes					1296:1309	the differential transcriptomes	1279:1309	the differential transcriptomes of the OGT variant-expressing stem cells	1279:1350	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	5	94	theme	thermodynamic	919:931	arg1	stability					933:941	thermodynamic stability	919:941	thermodynamic stability	919:941	Characterization of all five of these XLID missense variants of OGT demonstrates modest declines in thermodynamic stability and/or activities of the variants.
29769320	7	95	theme	Western	1169:1175	arg1	blotting					1177:1184	Western blotting	1169:1184	Western blotting	1169:1184	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29769320	8	96	theme	shared	1361:1366	arg1	deregulation					1368:1379	shared deregulation	1361:1379	shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development	1361:1526	However, analyses of the differential transcriptomes of the OGT variant-expressing stem cells revealed shared deregulation of genes involved in cell fate determination and liver X receptor/retinoid X receptor signaling, which has been implicated in neuronal development.
29769320	7	97	theme	global	1097:1102	arg1	profile					1113:1119	the global O-GlcNAc profile	1093:1119	the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels	1093:1164	Investigation of the global O-GlcNAc profile as well as OGT and O-GlcNAc hydrolase levels by Western blotting showed no gross changes in steady-state levels in the engineered lines.
29301852	5	0	theme	osteoblasts	1160:1170	arg1	differentiation					1127:1141	differentiation	1127:1141	differentiation	1127:1141	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	5	0	theme	osteoblasts	1160:1170	arg1	survival					1148:1155	survival	1148:1155	survival	1148:1155	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	5	0	theme	osteoblasts	1160:1170	arg1	proliferation					1112:1124	proliferation	1112:1124	proliferation	1112:1124	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	4	1	theme	O-linked	842:849	arg1	N-acetylglucosamine					851:869	O-linked N-acetylglucosamine	842:869	O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription	842:976	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	8	2	theme	adjunct	1602:1608	arg1	agents					1575:1580	cGMP-elevating agents	1560:1580	cGMP-elevating agents	1560:1580	These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.
29301852	8	2	theme	adjunct	1602:1608	arg1	treatment					1610:1618	an adjunct treatment	1599:1618	an adjunct treatment for diabetes-associated osteoporosis	1599:1655	These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.
29301852	1	3	theme	Bone	141:144	arg1	fractures					155:163	fractures	155:163	fractures	155:163	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	1	3	theme	Bone	141:144	arg1	complications					185:197	underrecognized complications	169:197	underrecognized complications of type 1 diabetes	169:216	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	1	3	theme	Bone	141:144	arg1	loss					146:149	Bone loss	141:149	Bone loss	141:149	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	4	4	theme	transcription	964:976	arg1	suppression					945:955	suppression	945:955	suppression of PKG transcription	945:976	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	4	4	theme	transcription	964:976	arg1	synthase-3					877:886	NO synthase-3	874:886	NO synthase-3	874:886	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	4	4	theme	transcription	964:976	arg1	inhibition					899:908	oxidative inhibition	889:908	oxidative inhibition of guanylate cyclase activity	889:938	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	3	5	theme	signal	642:647	arg1	pathway					662:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	2	6	from	dysfunction	320:330	arg1	diabetes					335:342	diabetes	335:342	diabetes	335:342	The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute.
29301852	3	7	theme	osteoblast	517:526	arg1	proliferation					528:540	osteoblast proliferation	517:540	osteoblast proliferation	517:540	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	8	8	used	used	1591:1594	arg2	treatment					1610:1618	an adjunct treatment	1599:1618	an adjunct treatment for diabetes-associated osteoporosis	1599:1655	These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.
29301852	8	8	used	used	1591:1594	arg2	agents					1575:1580	cGMP-elevating agents	1560:1580	cGMP-elevating agents	1560:1580	These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.
29301852	3	9	theme	PKG	679:681	arg1	stimulation					683:693	PKG stimulation	679:693	PKG stimulation of Akt	679:700	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	0	10	with	Function	78:85	arg1	Diabetes					131:138	Type 1 Diabetes	124:138	Type 1 Diabetes	124:138	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	7	11	theme	NADPH	1490:1494	arg1	production					1521:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	5	12	theme	NO-independent	993:1006	arg1	activator					1008:1016	Cinaciguat-an NO-independent activator	979:1016	Cinaciguat-an NO-independent activator of oxidized guanylate	979:1038	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	1	13	theme	impaired	243:250	arg1	formation					257:265	impaired bone formation	243:265	impaired bone formation by osteoblasts	243:280	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	0	14	theme	Bone	91:94	arg1	Formation					96:104	Bone Formation	91:104	Bone Formation	91:104	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	4	15	from	addition	830:837	arg1	part					818:821	part	818:821	part	818:821	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	4	16	theme	N-acetylglucosamine	851:869	arg1	addition					830:837	the addition	826:837	the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription	826:976	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	3	17	theme	nitric	563:568	arg1	NO					577:578	NO	577:578	NO	577:578	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	3	17	theme	nitric	563:568	arg1	oxide					570:574	the nitric oxide	559:574	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	1	18	theme	bone	252:255	arg1	formation					257:265	impaired bone formation	243:265	impaired bone formation by osteoblasts	243:280	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	0	19	theme	Male	109:112	arg1	Mice					114:117	Male Mice	109:117	Male Mice	109:117	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	3	20	theme	positive	713:720	arg1	loop					731:734	a positive feedback loop	711:734	a positive feedback loop	711:734	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	4	21	theme	high	763:766	arg1	glucose					768:774	high glucose	763:774	high glucose	763:774	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	2	22	theme	glycemic	402:409	arg1	control					411:417	poor glycemic control	397:417	poor glycemic control	397:417	The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute.
29301852	0	23	theme	Protein	0:6	arg1	Activation					17:26	Protein Kinase G Activation	0:26	Protein Kinase G Activation	0:26	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	0	24	theme	Kinase	8:13	arg1	Activation					17:26	Protein Kinase G Activation	0:26	Protein Kinase G Activation	0:26	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	7	25	theme	production	1521:1530	arg1	downregulation					1465:1478	downregulation	1465:1478	downregulation of excess NADPH oxidase-4-dependent H2O2 production	1465:1530	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	7	25	theme	production	1521:1530	arg1	induction					1430:1438	PKG-dependent induction	1416:1438	PKG-dependent induction of antioxidant genes	1416:1459	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	7	26	theme	high	1362:1365	arg1	glucose					1367:1373	high glucose	1362:1373	high glucose	1362:1373	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	4	27	theme	PKG	960:962	arg1	transcription					964:976	PKG transcription	960:976	PKG transcription	960:976	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	6	28	theme	cortical	1209:1216	arg1	bone					1218:1221	trabecular and cortical bone	1194:1221	trabecular and cortical bone	1194:1221	Cinaciguat increased trabecular and cortical bone in mice with type 1 diabetes by improving bone formation and osteocyte survival.
29301852	2	29	theme	insulin	377:383	arg1	deficiency					385:394	insulin deficiency	377:394	insulin deficiency	377:394	The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute.
29301852	2	30	theme	oxidative	446:454	arg1	stress					456:461	hyperglycemia-induced oxidative stress	424:461	hyperglycemia-induced oxidative stress	424:461	The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute.
29301852	8	31	theme	diabetes-associated	1624:1642	arg1	osteoporosis					1644:1655	diabetes-associated osteoporosis	1624:1655	diabetes-associated osteoporosis	1624:1655	These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.
29301852	6	32	theme	osteocyte	1284:1292	arg1	survival					1294:1301	osteocyte survival	1284:1301	osteocyte survival	1284:1301	Cinaciguat increased trabecular and cortical bone in mice with type 1 diabetes by improving bone formation and osteocyte survival.
29301852	0	33	with	Formation	96:104	arg1	Diabetes					131:138	Type 1 Diabetes	124:138	Type 1 Diabetes	124:138	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	7	34	theme	oxidative	1395:1403	arg1	stress					1405:1410	oxidative stress	1395:1410	oxidative stress	1395:1410	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	7	35	theme	antioxidant	1443:1453	arg1	genes					1455:1459	antioxidant genes	1443:1459	antioxidant genes	1443:1459	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	1	36	theme	underrecognized	169:183	arg1	fractures					155:163	fractures	155:163	fractures	155:163	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	1	36	theme	underrecognized	169:183	arg1	complications					185:197	underrecognized complications	169:197	underrecognized complications of type 1 diabetes	169:216	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	1	36	theme	underrecognized	169:183	arg1	loss					146:149	Bone loss	141:149	Bone loss	141:149	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	2	37	theme	hyperglycemia-induced	424:444	arg1	stress					456:461	hyperglycemia-induced oxidative stress	424:461	hyperglycemia-induced oxidative stress	424:461	The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute.
29301852	7	38	theme	H2O2	1516:1519	arg1	production					1521:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	5	39	theme	cGMP	1058:1061	arg1	synthesis					1063:1071	cGMP synthesis	1058:1071	cGMP synthesis	1058:1071	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	3	40	theme	oxide	570:574	arg1	monophosphate					598:610	the nitric oxide (NO)/cyclic guanosine monophosphate	559:610	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	3	40	theme	oxide	570:574	arg1	cGMP					613:616	cGMP	613:616	cGMP	613:616	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	5	41	theme	oxidized	1021:1028	arg1	guanylate					1030:1038	oxidized guanylate	1021:1038	oxidized guanylate	1021:1038	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	0	42	theme	G	15:15	arg1	Activation					17:26	Protein Kinase G Activation	0:26	Protein Kinase G Activation	0:26	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	3	43	theme	feedback	722:729	arg1	loop					731:734	a positive feedback loop	711:734	a positive feedback loop	711:734	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	3	44	theme	PKG	637:639	arg1	pathway					662:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	7	45	theme	genes	1455:1459	arg1	downregulation					1465:1478	downregulation	1465:1478	downregulation of excess NADPH oxidase-4-dependent H2O2 production	1465:1530	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	7	45	theme	genes	1455:1459	arg1	induction					1430:1438	PKG-dependent induction	1416:1438	PKG-dependent induction of antioxidant genes	1416:1459	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	0	46	theme	Oxidative	37:45	arg1	Stress					47:52	Oxidative Stress	37:52	Oxidative Stress	37:52	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	6	47	with	mice	1226:1229	arg1	diabetes					1243:1250	type 1 diabetes	1236:1250	type 1 diabetes	1236:1250	Cinaciguat increased trabecular and cortical bone in mice with type 1 diabetes by improving bone formation and osteocyte survival.
29301852	4	48	theme	cyclase	923:929	arg1	activity					931:938	guanylate cyclase activity	913:938	guanylate cyclase activity	913:938	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	0	49	from	Function	78:85	arg1	Mice					114:117	Male Mice	109:117	Male Mice	109:117	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	3	50	theme	monophosphate	598:610	arg1	pathway					662:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	7	51	theme	oxidase-4-dependent	1496:1514	arg1	production					1521:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	1	52	theme	type	202:205	arg1	diabetes					209:216	type 1 diabetes	202:216	type 1 diabetes	202:216	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	0	53	theme	Type	124:127	arg1	Diabetes					131:138	Type 1 Diabetes	124:138	Type 1 Diabetes	124:138	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	3	54	theme	G	634:634	arg1	pathway					662:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	4	55	link	O-linked	842:849	arg1	N-acetylglucosamine					851:869	O-linked N-acetylglucosamine	842:869	O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription	842:976	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	7	56	theme	PKG-dependent	1416:1428	arg1	induction					1430:1438	PKG-dependent induction	1416:1438	PKG-dependent induction of antioxidant genes	1416:1459	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	2	57	theme	poor	397:400	arg1	control					411:417	poor glycemic control	397:417	poor glycemic control	397:417	The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute.
29301852	3	58	theme	/cyclic	580:586	arg1	monophosphate					598:610	the nitric oxide (NO)/cyclic guanosine monophosphate	559:610	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	3	58	theme	/cyclic	580:586	arg1	cGMP					613:616	cGMP	613:616	cGMP	613:616	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	3	59	theme	Akt	698:700	arg1	stimulation					683:693	PKG stimulation	679:693	PKG stimulation of Akt	679:700	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	7	60	theme	diabetic	1318:1325	arg1	mice					1327:1330	diabetic mice	1318:1330	diabetic mice	1318:1330	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	4	61	theme	guanylate	913:921	arg1	cyclase					923:929	guanylate cyclase	913:929	guanylate cyclase activity	913:938	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	4	62	theme	NO	874:875	arg1	synthase-3					877:886	NO synthase-3	874:886	NO synthase-3	874:886	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	3	63	theme	guanosine	588:596	arg1	monophosphate					598:610	the nitric oxide (NO)/cyclic guanosine monophosphate	559:610	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	3	63	theme	guanosine	588:596	arg1	cGMP					613:616	cGMP	613:616	cGMP	613:616	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	7	64	from	mice	1327:1330	arg1	bones					1307:1311	bones	1307:1311	bones from diabetic mice	1307:1330	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	6	65	theme	type	1236:1239	arg1	diabetes					1243:1250	type 1 diabetes	1236:1250	type 1 diabetes	1236:1250	Cinaciguat increased trabecular and cortical bone in mice with type 1 diabetes by improving bone formation and osteocyte survival.
29301852	4	66	theme	oxidative	889:897	arg1	inhibition					899:908	oxidative inhibition	889:908	oxidative inhibition of guanylate cyclase activity	889:938	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	5	67	theme	Cinaciguat-an	979:991	arg1	activator					1008:1016	Cinaciguat-an NO-independent activator	979:1016	Cinaciguat-an NO-independent activator of oxidized guanylate	979:1038	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	3	68	theme	/protein	618:625	arg1	pathway					662:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	5	69	theme	guanylate	1030:1038	arg1	activator					1008:1016	Cinaciguat-an NO-independent activator	979:1016	Cinaciguat-an NO-independent activator of oxidized guanylate	979:1038	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	6	70	theme	trabecular	1194:1203	arg1	bone					1218:1221	trabecular and cortical bone	1194:1221	trabecular and cortical bone	1194:1221	Cinaciguat increased trabecular and cortical bone in mice with type 1 diabetes by improving bone formation and osteocyte survival.
29301852	1	71	theme	diabetes	209:216	arg1	fractures					155:163	fractures	155:163	fractures	155:163	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	1	71	theme	diabetes	209:216	arg1	complications					185:197	underrecognized complications	169:197	underrecognized complications of type 1 diabetes	169:216	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	1	71	theme	diabetes	209:216	arg1	loss					146:149	Bone loss	141:149	Bone loss	141:149	Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts.
29301852	7	72	theme	excess	1483:1488	arg1	production					1521:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	excess NADPH oxidase-4-dependent H2O2 production	1483:1530	In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production.
29301852	0	73	from	Formation	96:104	arg1	Mice					114:117	Male Mice	109:117	Male Mice	109:117	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	3	74	theme	kinase	627:632	arg1	pathway					662:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	2	75	theme	osteoblast	309:318	arg1	dysfunction					320:330	osteoblast dysfunction	309:330	osteoblast dysfunction in diabetes	309:342	The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute.
29301852	5	76	theme	diabetic	1079:1086	arg1	conditions					1088:1097	diabetic conditions	1079:1097	diabetic conditions	1079:1097	Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts.
29301852	0	77	theme	Osteoblast	67:76	arg1	Function					78:85	Osteoblast Function	67:85	Osteoblast Function	67:85	Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.
29301852	3	78	theme	transduction	649:660	arg1	pathway					662:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway	559:668	Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop.
29301852	6	79	theme	bone	1265:1268	arg1	formation					1270:1278	bone formation	1265:1278	bone formation	1265:1278	Cinaciguat increased trabecular and cortical bone in mice with type 1 diabetes by improving bone formation and osteocyte survival.
29301852	4	80	theme	NO/cGMP/PKG	777:787	arg1	signaling					789:797	NO/cGMP/PKG signaling	777:797	NO/cGMP/PKG signaling	777:797	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	8	81	theme	cGMP-elevating	1560:1573	arg1	agents					1575:1580	cGMP-elevating agents	1560:1580	cGMP-elevating agents	1560:1580	These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.
29301852	8	81	theme	cGMP-elevating	1560:1573	arg1	treatment					1610:1618	an adjunct treatment	1599:1618	an adjunct treatment for diabetes-associated osteoporosis	1599:1655	These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.
29301852	4	82	theme	activity	931:938	arg1	suppression					945:955	suppression	945:955	suppression of PKG transcription	945:976	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	4	82	theme	activity	931:938	arg1	synthase-3					877:886	NO synthase-3	874:886	NO synthase-3	874:886	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
29301852	4	82	theme	activity	931:938	arg1	inhibition					899:908	oxidative inhibition	889:908	oxidative inhibition of guanylate cyclase activity	889:938	In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription.
28924042	12	0	theme	alternative	1699:1709	arg1	processing					1711:1720	alternative processing	1699:1720	alternative processing of BMP proproteins	1699:1739	Furthermore, alternative processing of BMP proproteins produces ligands that signal through different receptors and exhibit specific developmental functions.
28924042	1	1	theme	numerous	228:235	arg1	roles					269:273	numerous developmental and physiological roles	228:273	numerous developmental and physiological roles	228:273	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	10	2	from	site	1501:1504	arg1	processing					1477:1486	processing	1477:1486	processing at the S1/S0 site	1477:1504	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	8	3	theme	NS	1177:1178	arg1	cleavage					1180:1187	Gbb NS cleavage	1173:1187	Gbb NS cleavage	1173:1187	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	5	4	theme	specific	791:798	arg1	ligands					800:806	specific ligands	791:806	specific ligands	791:806	We hypothesized that the Gbb prodomain is involved not only in regulating the production of specific ligands but also their signaling output.
28924042	4	5	theme	conventional	611:622	arg1	ligand					634:639	the conventional small BMP ligand	607:639	the conventional small BMP ligand	607:639	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	4	5	theme	conventional	611:622	arg1	Gbb15					600:604	Gbb15	600:604	Gbb15	600:604	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	7	6	theme	NS	1008:1009	arg1	cleavage					1011:1018	NS cleavage	1008:1018	NS cleavage	1008:1018	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	3	7	theme	distinct	522:529	arg1	forms					538:542	distinct ligand forms	522:542	distinct ligand forms	522:542	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	1	8	theme	morphogenetic	177:189	arg1	BMP					200:202	BMP	200:202	BMP	200:202	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	1	8	theme	morphogenetic	177:189	arg1	protein					191:197	bone morphogenetic protein	172:197	bone morphogenetic protein (BMP)	172:203	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	10	9	theme	O-linked	1520:1527	arg1	glycosylation					1529:1541	O-linked glycosylation	1520:1541	O-linked glycosylation in third instar larvae	1520:1564	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	9	10	theme	other	1397:1401	arg1	Punt					1420:1423	the other type II receptor Punt	1393:1423	the other type II receptor Punt	1393:1423	In fact, Gbb38-mediated signaling exhibits a preference for Wit over the other type II receptor Punt.
28924042	7	11	from	activity	1147:1154	arg1	culture					1164:1170	cell culture	1159:1170	cell culture	1159:1170	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	4	12	theme	NS	650:651	arg1	cleavage					658:665	NS site cleavage	650:665	NS site cleavage	650:665	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	0	13	theme	receptor	126:133	arg1	preferences					135:145	receptor preferences	126:145	receptor preferences	126:145	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	8	14	from	viability	1211:1219	arg1	manner					1316:1321	a type II receptor Wishful thinking (Wit)-dependent manner	1264:1321	a type II receptor Wishful thinking (Wit)-dependent manner	1264:1321	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	8	15	theme	ecdysis	1253:1259	arg1	regulation					1233:1242	its regulation	1229:1242	its regulation of pupal ecdysis	1229:1259	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	1	16	theme	developmental	237:249	arg1	roles					269:273	numerous developmental and physiological roles	228:273	numerous developmental and physiological roles	228:273	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	1	17	contain	has	224:226	arg1	family					152:157	The family	148:157	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins	148:222	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	1	17	contain	has	224:226	arg2	roles					269:273	numerous developmental and physiological roles	228:273	numerous developmental and physiological roles	228:273	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	4	18	from	S1	561:562	arg1	Cleavage					545:552	Cleavage	545:552	Cleavage at the S1 or atypical S0 site in Gbb	545:589	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	8	19	dep	-dependent	1305:1314	arg1	receptor					1274:1281	type II receptor	1266:1281	type II receptor	1266:1281	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	10	20	gly	glycosylation	1529:1541	arg1	larvae					1559:1564	third instar larvae	1546:1564	third instar larvae	1546:1564	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	6	21	theme	prodomain	917:925	arg1	association					886:896	association	886:896	association of the full-length prodomain with Gbb15	886:936	We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity.
28924042	3	22	theme	Glass	455:459	arg1	Gbb					474:476	Gbb	474:476	Gbb	474:476	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	22	theme	Glass	455:459	arg1	boat					468:471	Glass bottom boat	455:471	Glass bottom boat (Gbb)	455:477	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	22	theme	Glass	455:459	arg1	ortholog					500:507	the Drosophila BMP7 ortholog	480:507	the Drosophila BMP7 ortholog	480:507	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	23	theme	Multiple	414:421	arg1	sites					446:450	Multiple proteolytic processing sites	414:450	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog,	414:508	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	7	24	theme	Gbb15-Dpp	1125:1133	arg1	activity					1147:1154	Gbb15-Dpp heterodimer activity	1125:1154	Gbb15-Dpp heterodimer activity in cell culture	1125:1170	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	0	25	theme	morphogenetic	33:45	arg1	BMP					56:58	the bone morphogenetic protein (BMP)	24:59	the bone morphogenetic protein (BMP)	24:59	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	10	26	theme	third	1546:1550	arg1	larvae					1559:1564	third instar larvae	1546:1564	third instar larvae	1546:1564	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	0	27	theme	Alternative	0:10	arg1	Gbb					62:64	Gbb	62:64	Gbb	62:64	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	0	27	theme	Alternative	0:10	arg1	cleavage					12:19	Alternative cleavage	0:19	Alternative cleavage of the bone morphogenetic protein (BMP)	0:59	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	1	28	theme	physiological	255:267	arg1	roles					269:273	numerous developmental and physiological roles	228:273	numerous developmental and physiological roles	228:273	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	4	29	theme	Gbb38	685:689	arg1	ligand					691:696	a larger Gbb38 ligand	676:696	a larger Gbb38 ligand	676:696	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	2	30	theme	ligand	400:405	arg1	dimer					407:411	an active ligand dimer	390:411	an active ligand dimer	390:411	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	2	30	theme	ligand	400:405	arg1	domain					380:385	the C-terminal domain	365:385	the C-terminal domain	365:385	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	12	31	theme	different	1778:1786	arg1	receptors					1788:1796	different receptors	1778:1796	different receptors	1778:1796	Furthermore, alternative processing of BMP proproteins produces ligands that signal through different receptors and exhibit specific developmental functions.
28924042	6	32	theme	signaling	978:986	arg1	activity					988:995	signaling activity	978:995	signaling activity	978:995	We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity.
28924042	1	33	dep	TGF-β	162:166	arg1	proteins					215:222	signaling proteins	205:222	signaling proteins	205:222	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	3	34	theme	processing	435:444	arg1	sites					446:450	Multiple proteolytic processing sites	414:450	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog,	414:508	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	7	35	theme	wing	1092:1095	arg1	patterning					1102:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	7	35	theme	wing	1092:1095	arg1	Dpp					1066:1068	Dpp	1066:1068	Dpp	1066:1068	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	0	36	theme	bone	28:31	arg1	BMP					56:58	the bone morphogenetic protein (BMP)	24:59	the bone morphogenetic protein (BMP)	24:59	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	12	37	theme	BMP	1725:1727	arg1	proproteins					1729:1739	BMP proproteins	1725:1739	BMP proproteins	1725:1739	Furthermore, alternative processing of BMP proproteins produces ligands that signal through different receptors and exhibit specific developmental functions.
28924042	0	38	theme	BMP	56:58	arg1	Gbb					62:64	Gbb	62:64	Gbb	62:64	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	0	38	theme	BMP	56:58	arg1	cleavage					12:19	Alternative cleavage	0:19	Alternative cleavage of the bone morphogenetic protein (BMP)	0:59	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	3	39	from	sites	446:450	arg1	Gbb					474:476	Gbb	474:476	Gbb	474:476	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	39	from	sites	446:450	arg1	boat					468:471	Glass bottom boat	455:471	Glass bottom boat (Gbb)	455:477	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	39	from	sites	446:450	arg1	ortholog					500:507	the Drosophila BMP7 ortholog	480:507	the Drosophila BMP7 ortholog	480:507	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	0	40	theme	protein	47:53	arg1	BMP					56:58	the bone morphogenetic protein (BMP)	24:59	the bone morphogenetic protein (BMP)	24:59	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	11	41	theme	mature	1637:1642	arg1	ligand					1644:1649	the mature ligand	1633:1649	the mature ligand	1633:1649	Our findings demonstrate that BMP prodomain cleavage ensures that the mature ligand is not inhibited by the prodomain.
28924042	3	42	theme	bottom	461:466	arg1	Gbb					474:476	Gbb	474:476	Gbb	474:476	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	42	theme	bottom	461:466	arg1	boat					468:471	Glass bottom boat	455:471	Glass bottom boat (Gbb)	455:477	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	42	theme	bottom	461:466	arg1	ortholog					500:507	the Drosophila BMP7 ortholog	480:507	the Drosophila BMP7 ortholog	480:507	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	4	43	theme	small	624:628	arg1	ligand					634:639	the conventional small BMP ligand	607:639	the conventional small BMP ligand	607:639	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	4	43	theme	small	624:628	arg1	Gbb15					600:604	Gbb15	600:604	Gbb15	600:604	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	1	44	theme	signaling	205:213	arg1	proteins					215:222	signaling proteins	205:222	signaling proteins	205:222	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	4	45	theme	atypical	567:574	arg1	site					579:582	the S1 or atypical S0 site	557:582	site	579:582	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	7	46	theme	Gbb-Decapentaplegic	1045:1063	arg1	patterning					1102:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	7	46	theme	Gbb-Decapentaplegic	1045:1063	arg1	Dpp					1066:1068	Dpp	1066:1068	Dpp	1066:1068	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	2	47	theme	proprotein	331:340	arg1	convertases					342:352	proprotein convertases	331:352	proprotein convertases	331:352	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	11	48	theme	BMP	1597:1599	arg1	cleavage					1611:1618	BMP prodomain cleavage	1597:1618	BMP prodomain cleavage	1597:1618	Our findings demonstrate that BMP prodomain cleavage ensures that the mature ligand is not inhibited by the prodomain.
28924042	0	49	with	ligands	76:82	arg1	functions					112:120	distinct developmental functions	89:120	distinct developmental functions	89:120	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	0	49	with	ligands	76:82	arg1	preferences					135:145	receptor preferences	126:145	receptor preferences	126:145	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	9	50	theme	Gbb38-mediated	1333:1346	arg1	signaling					1348:1356	Gbb38-mediated signaling	1333:1356	Gbb38-mediated signaling	1333:1356	In fact, Gbb38-mediated signaling exhibits a preference for Wit over the other type II receptor Punt.
28924042	2	51	theme	proprotein	293:302	arg1	dimers					304:309	proprotein dimers	293:309	proprotein dimers	293:309	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	2	51	theme	proprotein	293:302	arg1	They					276:279	They	276:279	They	276:279	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	6	52	with	association	886:896	arg1	Gbb15					932:936	Gbb15	932:936	Gbb15	932:936	We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity.
28924042	3	53	theme	BMP7	495:498	arg1	ortholog					500:507	the Drosophila BMP7 ortholog	480:507	the Drosophila BMP7 ortholog	480:507	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	53	theme	BMP7	495:498	arg1	boat					468:471	Glass bottom boat	455:471	Glass bottom boat (Gbb)	455:477	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	5	54	theme	ligands	800:806	arg1	production					777:786	the production	773:786	the production of specific ligands	773:806	We hypothesized that the Gbb prodomain is involved not only in regulating the production of specific ligands but also their signaling output.
28924042	10	55	from	glycosylation	1529:1541	arg1	larvae					1559:1564	third instar larvae	1546:1564	third instar larvae	1546:1564	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	8	56	theme	Gbb	1173:1175	arg1	cleavage					1180:1187	Gbb NS cleavage	1173:1187	Gbb NS cleavage	1173:1187	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	7	57	theme	cell	1159:1162	arg1	culture					1164:1170	cell culture	1159:1170	cell culture	1159:1170	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	6	58	from	decrease	966:973	arg1	activity					988:995	signaling activity	978:995	signaling activity	978:995	We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity.
28924042	3	59	theme	ligand	531:536	arg1	forms					538:542	distinct ligand forms	522:542	distinct ligand forms	522:542	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	1	60	theme	TGF-β	162:166	arg1	family					152:157	The family	148:157	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins	148:222	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	6	61	theme	full-length	905:915	arg1	prodomain					917:925	the full-length prodomain	901:925	the full-length prodomain	901:925	We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity.
28924042	10	62	theme	S1/S0	1495:1499	arg1	site					1501:1504	the S1/S0 site	1491:1504	the S1/S0 site	1491:1504	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	0	63	theme	developmental	98:110	arg1	functions					112:120	distinct developmental functions	89:120	distinct developmental functions	89:120	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	10	64	link	O-linked	1520:1527	arg1	glycosylation					1529:1541	O-linked glycosylation	1520:1541	O-linked glycosylation in third instar larvae	1520:1564	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	1	65	theme	bone	172:175	arg1	BMP					200:202	BMP	200:202	BMP	200:202	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	1	65	theme	bone	172:175	arg1	protein					191:197	bone morphogenetic protein	172:197	bone morphogenetic protein (BMP)	172:203	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	4	66	from	site	579:582	arg1	Cleavage					545:552	Cleavage	545:552	Cleavage at the S1 or atypical S0 site in Gbb	545:589	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	1	67	theme	protein	191:197	arg1	family					152:157	The family	148:157	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins	148:222	The family of TGF-β and bone morphogenetic protein (BMP) signaling proteins has numerous developmental and physiological roles.
28924042	9	68	theme	type	1403:1406	arg1	Punt					1420:1423	the other type II receptor Punt	1393:1423	the other type II receptor Punt	1393:1423	In fact, Gbb38-mediated signaling exhibits a preference for Wit over the other type II receptor Punt.
28924042	6	69	theme	NS	864:865	arg1	cleavage					867:874	NS cleavage	864:874	NS cleavage	864:874	We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity.
28924042	9	70	theme	receptor	1411:1418	arg1	Punt					1420:1423	the other type II receptor Punt	1393:1423	the other type II receptor Punt	1393:1423	In fact, Gbb38-mediated signaling exhibits a preference for Wit over the other type II receptor Punt.
28924042	6	71	theme	concomitant	954:964	arg1	decrease					966:973	a concomitant decrease	952:973	a concomitant decrease in signaling activity	952:995	We found that blocking NS cleavage increased association of the full-length prodomain with Gbb15, resulting in a concomitant decrease in signaling activity.
28924042	4	72	theme	site	653:656	arg1	cleavage					658:665	NS site cleavage	650:665	NS site cleavage	650:665	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	3	73	theme	proteolytic	423:433	arg1	sites					446:450	Multiple proteolytic processing sites	414:450	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog,	414:508	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	8	74	theme	pupal	1247:1251	arg1	ecdysis					1253:1259	pupal ecdysis	1247:1259	pupal ecdysis	1247:1259	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	5	75	theme	signaling	823:831	arg1	output					833:838	their signaling output	817:838	their signaling output	817:838	We hypothesized that the Gbb prodomain is involved not only in regulating the production of specific ligands but also their signaling output.
28924042	0	76	theme	distinct	89:96	arg1	functions					112:120	distinct developmental functions	89:120	distinct developmental functions	89:120	Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences.
28924042	7	77	theme	heterodimer	1135:1145	arg1	activity					1147:1154	Gbb15-Dpp heterodimer activity	1125:1154	Gbb15-Dpp heterodimer activity in cell culture	1125:1170	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	8	78	theme	type	1266:1269	arg1	receptor					1274:1281	type II receptor	1266:1281	type II receptor	1266:1281	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	4	79	from	Cleavage	545:552	arg1	Gbb					587:589	Gbb	587:589	Gbb	587:589	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	12	80	theme	developmental	1819:1831	arg1	functions					1833:1841	specific developmental functions	1810:1841	specific developmental functions	1810:1841	Furthermore, alternative processing of BMP proproteins produces ligands that signal through different receptors and exhibit specific developmental functions.
28924042	10	81	theme	instar	1552:1557	arg1	larvae					1559:1564	third instar larvae	1546:1564	third instar larvae	1546:1564	Finally, we discovered that Gbb38 is produced when processing at the S1/S0 site is blocked by O-linked glycosylation in third instar larvae.
28924042	7	82	theme	vein	1097:1100	arg1	patterning					1102:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	7	82	theme	vein	1097:1100	arg1	Dpp					1066:1068	Dpp	1066:1068	Dpp	1066:1068	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	11	83	theme	prodomain	1601:1609	arg1	cleavage					1611:1618	BMP prodomain cleavage	1597:1618	BMP prodomain cleavage	1597:1618	Our findings demonstrate that BMP prodomain cleavage ensures that the mature ligand is not inhibited by the prodomain.
28924042	4	84	theme	larger	678:683	arg1	ligand					691:696	a larger Gbb38 ligand	676:696	a larger Gbb38 ligand	676:696	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	2	85	theme	active	393:398	arg1	dimer					407:411	an active ligand dimer	390:411	an active ligand dimer	390:411	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	2	85	theme	active	393:398	arg1	domain					380:385	the C-terminal domain	365:385	the C-terminal domain	365:385	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	7	86	theme	heterodimer-mediated	1071:1090	arg1	patterning					1102:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning	1045:1111	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	7	86	theme	heterodimer-mediated	1071:1090	arg1	Dpp					1066:1068	Dpp	1066:1068	Dpp	1066:1068	Moreover, NS cleavage was required in vivo for Gbb-Decapentaplegic (Dpp) heterodimer-mediated wing vein patterning but not for Gbb15-Dpp heterodimer activity in cell culture.
28924042	4	87	dep	produces	591:598	arg1	whereas					642:648	whereas	642:648	whereas	642:648	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	4	88	theme	BMP	630:632	arg1	ligand					634:639	the conventional small BMP ligand	607:639	the conventional small BMP ligand	607:639	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	4	88	theme	BMP	630:632	arg1	Gbb15					600:604	Gbb15	600:604	Gbb15	600:604	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	8	89	theme	-dependent	1305:1314	arg1	manner					1316:1321	a type II receptor Wishful thinking (Wit)-dependent manner	1264:1321	a type II receptor Wishful thinking (Wit)-dependent manner	1264:1321	Gbb NS cleavage was also required for viability through its regulation of pupal ecdysis in a type II receptor Wishful thinking (Wit)-dependent manner.
28924042	5	90	theme	Gbb	724:726	arg1	prodomain					728:736	the Gbb prodomain	720:736	the Gbb prodomain	720:736	We hypothesized that the Gbb prodomain is involved not only in regulating the production of specific ligands but also their signaling output.
28924042	12	91	theme	specific	1810:1817	arg1	functions					1833:1841	specific developmental functions	1810:1841	specific developmental functions	1810:1841	Furthermore, alternative processing of BMP proproteins produces ligands that signal through different receptors and exhibit specific developmental functions.
28924042	12	92	theme	proproteins	1729:1739	arg1	processing					1711:1720	alternative processing	1699:1720	alternative processing of BMP proproteins	1699:1739	Furthermore, alternative processing of BMP proproteins produces ligands that signal through different receptors and exhibit specific developmental functions.
28924042	2	93	theme	C-terminal	369:378	arg1	dimer					407:411	an active ligand dimer	390:411	an active ligand dimer	390:411	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	2	93	theme	C-terminal	369:378	arg1	domain					380:385	the C-terminal domain	365:385	the C-terminal domain	365:385	They are made as proprotein dimers and then cleaved by proprotein convertases to release the C-terminal domain as an active ligand dimer.
28924042	4	94	theme	S0	576:577	arg1	site					579:582	the S1 or atypical S0 site	557:582	site	579:582	Cleavage at the S1 or atypical S0 site in Gbb produces Gbb15, the conventional small BMP ligand, whereas NS site cleavage produces a larger Gbb38 ligand.
28924042	3	95	theme	Drosophila	484:493	arg1	ortholog					500:507	the Drosophila BMP7 ortholog	480:507	the Drosophila BMP7 ortholog	480:507	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28924042	3	95	theme	Drosophila	484:493	arg1	boat					468:471	Glass bottom boat	455:471	Glass bottom boat (Gbb)	455:477	Multiple proteolytic processing sites in Glass bottom boat (Gbb), the Drosophila BMP7 ortholog, can produce distinct ligand forms.
28830009	0	0	theme	InVitro	95:101	arg1	Analysis					112:119	InVitro Efficacy Analysis	95:119	InVitro Efficacy Analysis	95:119	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	0	0	theme	InVitro	95:101	arg1	Humanization					0:11	Humanization	0:11	Humanization of JAA-F11	0:22	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	10	1	contain	has	1622:1624	arg2	therapy					1650:1656	an adjunct therapy	1639:1656	an adjunct therapy	1639:1656	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	1	contain	has	1622:1624	arg2	potential					1626:1634	potential	1626:1634	potential	1626:1634	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	1	contain	has	1622:1624	arg1	antibody					1600:1607	the humanized antibody	1586:1607	the humanized antibody to the TF-Ag	1586:1620	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	9	2	theme	naked	1377:1381	arg1	hJAA-F11					1383:1390	the naked hJAA-F11	1373:1390	the naked hJAA-F11	1373:1390	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	7	3	theme	flow	1213:1216	arg1	cytometry					1218:1226	flow cytometry	1213:1226	flow cytometry	1213:1226	The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry.
28830009	9	4	theme	cancer	1499:1504	arg1	model					1516:1520	a human breast cancer xenograft model	1484:1520	a human breast cancer xenograft model	1484:1520	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	1	5	theme	normal	393:398	arg1	cells					400:404	normal cells	393:404	normal cells	393:404	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	5	6	theme	target	745:750	arg1	array					759:763	a 609 target glycan array	739:763	a 609 target glycan array	739:763	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	9	7	theme	maytansine-conjugated	1398:1418	arg1	hJAA-F11-DM1					1430:1441	hJAA-F11-DM1	1430:1441	hJAA-F11-DM1	1430:1441	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	9	7	theme	maytansine-conjugated	1398:1418	arg1	antibody					1420:1427	a maytansine-conjugated antibody	1396:1427	a maytansine-conjugated antibody (hJAA-F11-DM1)	1396:1442	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	2	8	theme	cancer	484:489	arg1	types					491:495	multiple cancer types	475:495	multiple cancer types	475:495	JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types.
28830009	10	9	dep	either	1659:1664	arg1	directly					1666:1673	directly	1666:1673	directly	1666:1673	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	5	10	theme	beta-linked	902:912	arg1	structures					914:923	TF-Ag beta-linked structures	896:923	TF-Ag beta-linked structures	896:923	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	0	11	theme	Efficacy	103:110	arg1	Analysis					112:119	InVitro Efficacy Analysis	95:119	InVitro Efficacy Analysis	95:119	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	0	11	theme	Efficacy	103:110	arg1	Humanization					0:11	Humanization	0:11	Humanization of JAA-F11	0:22	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	7	12	from	cytotoxicity	1143:1154	arg1	lines					1181:1185	breast and lung tumor lines	1159:1185	breast and lung tumor lines shown to express TF-Ag by flow cytometry	1159:1226	The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry.
28830009	10	13	dep	conjugate	1706:1714	arg1	treat					1720:1724	treat	1720:1724	to treat breast cancer	1717:1738	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	8	14	theme	binding	1306:1312	arg1	ELISA					1314:1318	a surface binding ELISA	1296:1318	a surface binding ELISA	1296:1318	Internalization of hJAA-F11 into cancer cells was also shown using a surface binding ELISA and confirmed by immunofluorescence microscopy.
28830009	6	15	theme	constructs	966:975	arg1	affinity					939:946	The relative affinity	926:946	The relative affinity of these hJAA-F11 constructs for TF-Ag	926:985	The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity.
28830009	7	16	theme	lung	1170:1173	arg1	lines					1181:1185	breast and lung tumor lines	1159:1185	breast and lung tumor lines shown to express TF-Ag by flow cytometry	1159:1226	The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry.
28830009	5	17	contain	have	802:805	arg2	specificity					826:836	excellent chemical specificity	807:836	excellent chemical specificity	807:836	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	5	17	contain	have	802:805	arg1	constructs					777:786	2 hJAA-F11 constructs	766:786	2 hJAA-F11 constructs	766:786	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	4	18	dep	specificity	653:663	arg1	the					649:651	the	649:651	the	649:651	The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).
28830009	4	18	dep	specificity	653:663	arg1	efficacy					687:694	efficacy	687:694	efficacy	687:694	The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).
28830009	1	19	theme	Thomsen-Friedenreich	175:194	arg1	antigen					252:258	an alpha-O-linked disaccharide antigen	221:258	an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers	221:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	19	theme	Thomsen-Friedenreich	175:194	arg1	TF-Ag					205:209	TF-Ag	205:209	TF-Ag	205:209	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	19	theme	Thomsen-Friedenreich	175:194	arg1	cryptic					382:388	cryptic	382:388	cryptic	382:388	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	19	theme	Thomsen-Friedenreich	175:194	arg1	Antigen					196:202	the Thomsen-Friedenreich Antigen	171:202	the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells	171:404	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	5	20	theme	glycan	752:757	arg1	array					759:763	a 609 target glycan array	739:763	a 609 target glycan array	739:763	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	2	21	contain	has	415:417	arg2	potential					419:427	potential	419:427	potential	419:427	JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types.
28830009	2	21	contain	has	415:417	arg1	JAA-F11					407:413	JAA-F11	407:413	JAA-F11	407:413	JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types.
28830009	9	22	theme	human	1486:1490	arg1	model					1516:1520	a human breast cancer xenograft model	1484:1520	a human breast cancer xenograft model	1484:1520	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	5	23	theme	excellent	807:815	arg1	specificity					826:836	excellent chemical specificity	807:836	excellent chemical specificity	807:836	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	7	24	theme	breast	1159:1164	arg1	lines					1181:1185	breast and lung tumor lines	1159:1185	breast and lung tumor lines shown to express TF-Ag by flow cytometry	1159:1226	The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry.
28830009	6	25	theme	relative	930:937	arg1	affinity					939:946	The relative affinity	926:946	The relative affinity of these hJAA-F11 constructs for TF-Ag	926:985	The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity.
28830009	4	26	theme	humanized	703:711	arg1	JAA-F11					713:719	the humanized JAA-F11	699:719	the humanized JAA-F11 (hJAA-F11)	699:730	The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).
28830009	4	26	theme	humanized	703:711	arg1	hJAA-F11					722:729	hJAA-F11	722:729	hJAA-F11	722:729	The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).
28830009	5	27	theme	chemical	817:824	arg1	specificity					826:836	excellent chemical specificity	807:836	excellent chemical specificity	807:836	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	1	28	theme	%	281:281	arg1	surface					267:273	the surface	263:273	the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers	263:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	10	29	theme	targeted	1804:1811	arg1	therapy					1813:1819	no targeted therapy	1801:1819	no targeted therapy	1801:1819	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	1	30	link	alpha-O-linked	224:237	arg1	antigen					252:258	an alpha-O-linked disaccharide antigen	221:258	an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers	221:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	30	link	alpha-O-linked	224:237	arg1	cryptic					382:388	cryptic	382:388	cryptic	382:388	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	30	link	alpha-O-linked	224:237	arg1	Antigen					196:202	the Thomsen-Friedenreich Antigen	171:202	the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells	171:404	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	8	31	theme	immunofluorescence	1337:1354	arg1	microscopy					1356:1365	immunofluorescence microscopy	1337:1365	immunofluorescence microscopy	1337:1365	Internalization of hJAA-F11 into cancer cells was also shown using a surface binding ELISA and confirmed by immunofluorescence microscopy.
28830009	9	32	theme	in	1455:1456	arg1	progression					1469:1479	in vivo tumor progression	1455:1479	in vivo tumor progression	1455:1479	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	10	33	theme	humanized	1590:1598	arg1	antibody					1600:1607	the humanized antibody	1586:1607	the humanized antibody to the TF-Ag	1586:1620	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	34	theme	triple	1751:1756	arg1	cancer					1774:1779	triple negative breast cancer	1751:1779	triple negative breast cancer which currently has no targeted therapy	1751:1819	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	3	35	theme	JAA-F11	514:520	arg1	Humanization					498:509	Humanization	498:509	Humanization	498:509	Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework.
28830009	10	36	dep	therapy	1650:1656	arg1	part					1681:1684	part	1681:1684	part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer	1681:1843	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	36	dep	therapy	1650:1656	arg1	either					1659:1664	either	1659:1664	either	1659:1664	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	6	37	theme	mouse	1009:1013	arg1	antibody					1015:1022	the mouse antibody	1005:1022	the mouse antibody	1005:1022	The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity.
28830009	0	38	theme	JAA-F11	16:22	arg1	Analysis					112:119	InVitro Efficacy Analysis	95:119	InVitro Efficacy Analysis	95:119	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	0	38	theme	JAA-F11	16:22	arg1	Humanization					0:11	Humanization	0:11	Humanization of JAA-F11	0:22	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	0	38	theme	JAA-F11	16:22	arg1	Antibody					82:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	1	39	theme	human	286:290	arg1	cancers					366:372	prostate cancers	357:372	prostate cancers	357:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	39	theme	human	286:290	arg1	breast					314:319	breast	314:319	breast	314:319	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	39	theme	human	286:290	arg1	bladder					335:341	bladder	335:341	bladder	335:341	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	39	theme	human	286:290	arg1	ovarian					344:350	ovarian	344:350	ovarian	344:350	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	39	theme	human	286:290	arg1	lung					322:325	lung	322:325	lung	322:325	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	39	theme	human	286:290	arg1	carcinomas					292:301	human carcinomas	286:301	human carcinomas	286:301	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	39	theme	human	286:290	arg1	colon					328:332	colon	328:332	colon	328:332	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	10	40	theme	drug	1701:1704	arg1	conjugate					1706:1714	an antibody drug conjugate	1689:1714	an antibody drug conjugate	1689:1714	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	4	41	theme	JAA-F11	713:719	arg1	biology					679:685	biology	679:685	biology	679:685	The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).
28830009	4	41	theme	JAA-F11	713:719	arg1	affinity					666:673	affinity	666:673	affinity	666:673	The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).
28830009	4	41	theme	JAA-F11	713:719	arg1	specificity					653:663	specificity	653:663	specificity	653:663	The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).
28830009	9	42	theme	SCID	1525:1528	arg1	mice					1530:1533	SCID mice	1525:1533	SCID mice	1525:1533	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	9	43	theme	xenograft	1506:1514	arg1	model					1516:1520	a human breast cancer xenograft model	1484:1520	a human breast cancer xenograft model	1484:1520	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	7	44	theme	antibody-dependent	1115:1132	arg1	cytotoxicity					1143:1154	antibody-dependent cellular cytotoxicity	1115:1154	antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry	1115:1226	The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry.
28830009	1	45	theme	carcinomas	292:301	arg1	cancers					366:372	prostate cancers	357:372	prostate cancers	357:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	45	theme	carcinomas	292:301	arg1	breast					314:319	breast	314:319	breast	314:319	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	45	theme	carcinomas	292:301	arg1	bladder					335:341	bladder	335:341	bladder	335:341	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	45	theme	carcinomas	292:301	arg1	%					281:281	~80%	278:281	~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers	278:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	45	theme	carcinomas	292:301	arg1	ovarian					344:350	ovarian	344:350	ovarian	344:350	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	45	theme	carcinomas	292:301	arg1	lung					322:325	lung	322:325	lung	322:325	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	45	theme	carcinomas	292:301	arg1	carcinomas					292:301	human carcinomas	286:301	human carcinomas	286:301	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	45	theme	carcinomas	292:301	arg1	colon					328:332	colon	328:332	colon	328:332	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	46	theme	prostate	357:364	arg1	cancers					366:372	prostate cancers	357:372	prostate cancers	357:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	3	47	theme	determining	563:573	arg1	regions					575:581	complementarity determining regions	547:581	complementarity determining regions grafting on a homology framework	547:614	Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework.
28830009	8	48	theme	cancer	1262:1267	arg1	cells					1269:1273	cancer cells	1262:1273	cancer cells	1262:1273	Internalization of hJAA-F11 into cancer cells was also shown using a surface binding ELISA and confirmed by immunofluorescence microscopy.
28830009	6	49	theme	T20	1031:1033	arg1	scoring					1035:1041	T20 scoring	1031:1041	T20 scoring	1031:1041	The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity.
28830009	7	50	theme	cellular	1134:1141	arg1	cytotoxicity					1143:1154	antibody-dependent cellular cytotoxicity	1115:1154	antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry	1115:1226	The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry.
28830009	9	51	dep	in	1455:1456	arg1	vivo					1458:1461	vivo	1458:1461	vivo	1458:1461	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	7	52	theme	tumor	1175:1179	arg1	lines					1181:1185	breast and lung tumor lines	1159:1185	breast and lung tumor lines shown to express TF-Ag by flow cytometry	1159:1226	The hJAA-F11 constructs produced antibody-dependent cellular cytotoxicity in breast and lung tumor lines shown to express TF-Ag by flow cytometry.
28830009	0	53	theme	Anti-Thomsen-Friedenreich	43:67	arg1	Humanization					0:11	Humanization	0:11	Humanization of JAA-F11	0:22	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	0	53	theme	Anti-Thomsen-Friedenreich	43:67	arg1	Antibody					82:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	10	54	theme	antibody	1692:1699	arg1	conjugate					1706:1714	an antibody drug conjugate	1689:1714	an antibody drug conjugate	1689:1714	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	1	55	from	antigen	252:258	arg1	surface					267:273	the surface	263:273	the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers	263:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	5	56	link	beta-linked	902:912	arg1	structures					914:923	TF-Ag beta-linked structures	896:923	TF-Ag beta-linked structures	896:923	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	10	57	theme	negative	1758:1765	arg1	cancer					1774:1779	triple negative breast cancer	1751:1779	triple negative breast cancer which currently has no targeted therapy	1751:1819	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	5	58	theme	TF-Ag	855:859	arg1	structures					874:883	TF-Ag alpha-linked structures	855:883	TF-Ag alpha-linked structures	855:883	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	0	59	theme	Specific	34:41	arg1	Humanization					0:11	Humanization	0:11	Humanization of JAA-F11	0:22	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	0	59	theme	Specific	34:41	arg1	Antibody					82:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	10	60	theme	conjugate	1706:1714	arg1	part					1681:1684	part	1681:1684	part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer	1681:1843	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	8	61	theme	surface	1298:1304	arg1	ELISA					1314:1318	a surface binding ELISA	1296:1318	a surface binding ELISA	1296:1318	Internalization of hJAA-F11 into cancer cells was also shown using a surface binding ELISA and confirmed by immunofluorescence microscopy.
28830009	3	62	theme	complementarity	547:561	arg1	regions					575:581	complementarity determining regions	547:581	complementarity determining regions grafting on a homology framework	547:614	Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework.
28830009	9	63	theme	tumor	1463:1467	arg1	progression					1469:1479	in vivo tumor progression	1455:1479	in vivo tumor progression	1455:1479	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	5	64	theme	alpha-linked	861:872	arg1	structures					874:883	TF-Ag alpha-linked structures	855:883	TF-Ag alpha-linked structures	855:883	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	10	65	theme	breast	1726:1731	arg1	cancer					1733:1738	breast cancer	1726:1738	breast cancer	1726:1738	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	66	theme	lung	1833:1836	arg1	cancer					1838:1843	lung cancer	1833:1843	lung cancer	1833:1843	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	67	theme	breast	1767:1772	arg1	cancer					1774:1779	triple negative breast cancer	1751:1779	triple negative breast cancer which currently has no targeted therapy	1751:1819	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	9	68	theme	breast	1492:1497	arg1	model					1516:1520	a human breast cancer xenograft model	1484:1520	a human breast cancer xenograft model	1484:1520	Both the naked hJAA-F11 and a maytansine-conjugated antibody (hJAA-F11-DM1) suppressed in vivo tumor progression in a human breast cancer xenograft model in SCID mice.
28830009	5	69	theme	TF-Ag	896:900	arg1	structures					914:923	TF-Ag beta-linked structures	896:923	TF-Ag beta-linked structures	896:923	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	1	70	theme	alpha-O-linked	224:237	arg1	antigen					252:258	an alpha-O-linked disaccharide antigen	221:258	an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers	221:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	70	theme	alpha-O-linked	224:237	arg1	cryptic					382:388	cryptic	382:388	cryptic	382:388	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	70	theme	alpha-O-linked	224:237	arg1	Antigen					196:202	the Thomsen-Friedenreich Antigen	171:202	the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells	171:404	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	5	71	link	alpha-linked	861:872	arg1	structures					874:883	TF-Ag alpha-linked structures	855:883	TF-Ag alpha-linked structures	855:883	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	10	72	contain	has	1797:1799	arg1	cancer					1774:1779	triple negative breast cancer	1751:1779	triple negative breast cancer which currently has no targeted therapy	1751:1819	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	72	contain	has	1797:1799	arg2	therapy					1813:1819	no targeted therapy	1801:1819	no targeted therapy	1801:1819	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	72	contain	has	1797:1799	arg1	cancer					1838:1843	lung cancer	1833:1843	lung cancer	1833:1843	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	3	73	theme	homology	597:604	arg1	framework					606:614	a homology framework	595:614	a homology framework	595:614	Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework.
28830009	10	74	theme	adjunct	1642:1648	arg1	therapy					1650:1656	an adjunct therapy	1639:1656	an adjunct therapy	1639:1656	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	10	74	theme	adjunct	1642:1648	arg1	potential					1626:1634	potential	1626:1634	potential	1626:1634	Together, our results support the conclusion that the humanized antibody to the TF-Ag has potential as an adjunct therapy, either directly or as part of an antibody drug conjugate, to treat breast cancer, including triple negative breast cancer which currently has no targeted therapy, as well as lung cancer.
28830009	1	75	theme	specific	142:149	arg1	mouse					151:155	a highly specific mouse	133:155	a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells	133:404	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	75	theme	specific	142:149	arg1	JAA-F11					122:128	JAA-F11	122:128	JAA-F11	122:128	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	76	theme	disaccharide	239:250	arg1	antigen					252:258	an alpha-O-linked disaccharide antigen	221:258	an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers	221:372	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	76	theme	disaccharide	239:250	arg1	cryptic					382:388	cryptic	382:388	cryptic	382:388	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	76	theme	disaccharide	239:250	arg1	Antigen					196:202	the Thomsen-Friedenreich Antigen	171:202	the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells	171:404	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	2	77	theme	cancer	450:455	arg1	immunotherapy					457:469	cancer immunotherapy	450:469	cancer immunotherapy for multiple cancer types	450:495	JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types.
28830009	6	78	theme	low	1053:1055	arg1	immunogenicity					1066:1079	low clinical immunogenicity	1053:1079	low clinical immunogenicity	1053:1079	The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity.
28830009	8	79	theme	hJAA-F11	1248:1255	arg1	Internalization					1229:1243	Internalization	1229:1243	Internalization of hJAA-F11 into cancer cells	1229:1273	Internalization of hJAA-F11 into cancer cells was also shown using a surface binding ELISA and confirmed by immunofluorescence microscopy.
28830009	6	80	theme	clinical	1057:1064	arg1	immunogenicity					1066:1079	low clinical immunogenicity	1053:1079	low clinical immunogenicity	1053:1079	The relative affinity of these hJAA-F11 constructs for TF-Ag was improved over the mouse antibody, while T20 scoring predicted low clinical immunogenicity.
28830009	0	81	theme	Pancarcinoma	69:80	arg1	Humanization					0:11	Humanization	0:11	Humanization of JAA-F11	0:22	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	0	81	theme	Pancarcinoma	69:80	arg1	Antibody					82:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody	25:89	Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and InVitro Efficacy Analysis.
28830009	5	82	theme	hJAA-F11	768:775	arg1	constructs					777:786	2 hJAA-F11 constructs	766:786	2 hJAA-F11 constructs	766:786	Using a 609 target glycan array, 2 hJAA-F11 constructs were shown to have excellent chemical specificity, binding only to TF-Ag alpha-linked structures and not to TF-Ag beta-linked structures.
28830009	1	83	theme	monoclonal	157:166	arg1	mouse					151:155	a highly specific mouse	133:155	a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells	133:404	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	1	83	theme	monoclonal	157:166	arg1	JAA-F11					122:128	JAA-F11	122:128	JAA-F11	122:128	JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells.
28830009	2	84	theme	multiple	475:482	arg1	types					491:495	multiple cancer types	475:495	multiple cancer types	475:495	JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types.
29437916	0	0	theme	dystrophy	79:87	arg1	marker					41:46	a marker	39:46	a marker of GMPPB gene-related muscular dystrophy	39:87	Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.
29437916	5	1	theme	GMPPB-associated	800:815	arg1	dystroglycanopathy					817:834	GMPPB-associated dystroglycanopathy	800:834	GMPPB-associated dystroglycanopathy	800:834	METHODS We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy.
29437916	10	2	theme	β-DG	1378:1381	arg1	mobility					1399:1406	β-DG electrophoretic mobility	1378:1406	β-DG electrophoretic mobility in patients with dystroglycanopathy	1378:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	1	3	theme	congenital	266:275	arg1	dystrophies					286:296	congenital muscular dystrophies	266:296	congenital muscular dystrophies	266:296	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	0	4	theme	muscular	70:77	arg1	dystrophy					79:87	GMPPB gene-related muscular dystrophy	51:87	GMPPB gene-related muscular dystrophy	51:87	Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.
29437916	9	5	theme	β-DG	1322:1325	arg1	glycosylation					1305:1317	abnormal N-linked glycosylation	1287:1317	abnormal N-linked glycosylation of β-DG	1287:1325	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	10	6	theme	defect	1485:1490	arg1	change					1368:1373	a change	1366:1373	a change in β-DG electrophoretic mobility in patients with dystroglycanopathy	1366:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	10	6	theme	defect	1485:1490	arg1	marker					1461:1466	a distinctive marker	1447:1466	a distinctive marker of the molecular defect in GMPPB	1447:1499	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	1	7	theme	autosomal-recessive	161:179	arg1	disorders					181:189	autosomal-recessive disorders	161:189	autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies	161:339	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	9	8	gly	glycosylation	1305:1317	arg1	β-DG					1322:1325	β-DG	1322:1325	β-DG	1322:1325	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	1	9	theme	muscular	277:284	arg1	dystrophies					286:296	congenital muscular dystrophies	266:296	congenital muscular dystrophies	266:296	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	5	10	theme	biochemical	759:769	arg1	findings					771:778	clinical, genetic and biochemical findings	737:778	clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy	737:834	METHODS We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy.
29437916	6	11	theme	condition	958:966	arg1	features					941:948	clinical and muscle MRI features	917:948	features	941:948	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	10	12	theme	molecular	1475:1483	arg1	defect					1485:1490	the molecular defect	1471:1490	the molecular defect in GMPPB	1471:1499	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	7	13	theme	consistent	994:1003	arg1	shift					1005:1009	a consistent shift	992:1009	a consistent shift in the mobility of beta-dystroglycan (β-DG)	992:1053	In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean.
29437916	8	14	theme	large	1172:1176	arg1	cohort					1197:1202	our large dystroglycanopathy cohort	1168:1202	our large dystroglycanopathy cohort	1168:1202	This was only observed in patients with GMPPB in our large dystroglycanopathy cohort.
29437916	4	15	theme	parallel	665:672	arg1	analysis					688:695	parallel or sequential analysis	665:695	parallel or sequential analysis of all known genes	665:714	With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes.
29437916	7	16	theme	Western	1058:1064	arg1	analysis					1071:1078	Western blot analysis	1058:1078	Western blot analysis of all patients analysed by this mean	1058:1116	In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean.
29437916	6	17	theme	novel	861:865	arg1	mutations					867:875	eight novel mutations	855:875	eight novel mutations	855:875	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	6	18	dep	RESULTS	837:843	arg1	report					848:853	report	848:853	report eight novel mutations	848:875	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	6	18	dep	RESULTS	837:843	arg1	expand					889:894	expand	889:894	further expand current knowledge on clinical and muscle MRI features of this condition	881:966	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	3	19	theme	mannose	529:535	arg1	GMPPB					558:562	GMPPB	558:562	GMPPB	558:562	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	3	19	theme	mannose	529:535	arg1	B					555:555	guanosine diphosphate mannose pyrophosphorylase B	507:555	guanosine diphosphate mannose pyrophosphorylase B (GMPPB)	507:563	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	3	20	theme	pyrophosphorylase	537:553	arg1	GMPPB					558:562	GMPPB	558:562	GMPPB	558:562	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	3	20	theme	pyrophosphorylase	537:553	arg1	B					555:555	guanosine diphosphate mannose pyrophosphorylase B	507:555	guanosine diphosphate mannose pyrophosphorylase B (GMPPB)	507:563	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	10	21	dep	CONCLUSIONS	1328:1338	arg1	demonstrate					1349:1359	demonstrate	1349:1359	demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB	1349:1499	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	3	22	theme	guanosine	507:515	arg1	GMPPB					558:562	GMPPB	558:562	GMPPB	558:562	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	3	22	theme	guanosine	507:515	arg1	B					555:555	guanosine diphosphate mannose pyrophosphorylase B	507:555	guanosine diphosphate mannose pyrophosphorylase B (GMPPB)	507:563	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	3	23	theme	Recessive	464:472	arg1	mutations					474:482	Recessive mutations	464:482	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB),	464:564	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	10	24	from	change	1368:1373	arg1	mobility					1399:1406	β-DG electrophoretic mobility	1378:1406	β-DG electrophoretic mobility in patients with dystroglycanopathy	1378:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	5	25	dep	METHODS	717:723	arg1	describe					728:735	describe	728:735	describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy	728:834	METHODS We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy.
29437916	9	26	theme	mobility	1238:1245	arg1	shift					1247:1251	this mobility shift	1233:1251	this mobility shift in patients with GMPPB	1233:1274	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	2	27	theme	α-DG	439:442	arg1	glycoepitopes					422:434	glycoepitopes	422:434	glycoepitopes of α-DG on a muscle biopsy	422:461	Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy.
29437916	6	28	theme	MRI	937:939	arg1	features					941:948	clinical and muscle MRI features	917:948	features	941:948	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	5	29	theme	patients	786:793	arg1	findings					771:778	clinical, genetic and biochemical findings	737:778	clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy	737:834	METHODS We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy.
29437916	1	30	theme	wide	196:199	arg1	heterogeneity					222:234	wide clinical and genetic heterogeneity	196:234	wide clinical and genetic heterogeneity	196:234	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	0	31	theme	Mobility	0:7	arg1	shift					9:13	Mobility shift	0:13	Mobility shift of beta-dystroglycan	0:34	Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.
29437916	10	32	theme	distinctive	1449:1459	arg1	change					1368:1373	a change	1366:1373	a change in β-DG electrophoretic mobility in patients with dystroglycanopathy	1366:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	10	32	theme	distinctive	1449:1459	arg1	marker					1461:1466	a distinctive marker	1447:1466	a distinctive marker of the molecular defect in GMPPB	1447:1499	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	1	33	theme	BACKGROUND	90:99	arg1	Defects					101:107	BACKGROUND Defects	90:107	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG)	90:153	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	1	34	theme	clinical	201:208	arg1	heterogeneity					222:234	wide clinical and genetic heterogeneity	196:234	wide clinical and genetic heterogeneity	196:234	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	0	35	theme	beta-dystroglycan	18:34	arg1	shift					9:13	Mobility shift	0:13	Mobility shift of beta-dystroglycan	0:34	Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.
29437916	5	36	with	patients	786:793	arg1	dystroglycanopathy					817:834	GMPPB-associated dystroglycanopathy	800:834	GMPPB-associated dystroglycanopathy	800:834	METHODS We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy.
29437916	1	37	with	heterogeneity	222:234	arg1	phenotypes					242:251	phenotypes	242:251	phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies	242:339	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	10	38	from	defect	1485:1490	arg1	GMPPB					1495:1499	GMPPB	1495:1499	GMPPB	1495:1499	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	1	39	theme	girdle	313:318	arg1	dystrophies					329:339	milder limb girdle muscular dystrophies	301:339	milder limb girdle muscular dystrophies	301:339	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	1	40	gly	glycosylation	112:124	arg1	alpha-dystroglycan					129:146	alpha-dystroglycan	129:146	alpha-dystroglycan (α-DG)	129:153	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	1	40	gly	glycosylation	112:124	arg1	α-DG					149:152	α-DG	149:152	α-DG	149:152	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	6	41	theme	muscle	930:935	arg1	features					941:948	clinical and muscle MRI features	917:948	features	941:948	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	10	42	from	marker	1461:1466	arg1	GMPPB					1495:1499	GMPPB	1495:1499	GMPPB	1495:1499	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	9	43	with	patients	1256:1263	arg1	GMPPB					1270:1274	GMPPB	1270:1274	GMPPB	1270:1274	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	1	44	theme	genetic	214:220	arg1	heterogeneity					222:234	wide clinical and genetic heterogeneity	196:234	wide clinical and genetic heterogeneity	196:234	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	1	45	theme	muscular	320:327	arg1	dystrophies					329:339	milder limb girdle muscular dystrophies	301:339	milder limb girdle muscular dystrophies	301:339	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	5	46	theme	genetic	747:753	arg1	findings					771:778	clinical, genetic and biochemical findings	737:778	clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy	737:834	METHODS We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy.
29437916	4	47	theme	known	704:708	arg1	genes					710:714	all known genes	700:714	all known genes	700:714	With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes.
29437916	2	48	theme	muscle	449:454	arg1	biopsy					456:461	a muscle biopsy	447:461	a muscle biopsy	447:461	Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy.
29437916	7	49	from	shift	1005:1009	arg1	mobility					1018:1025	the mobility	1014:1025	the mobility of beta-dystroglycan (β-DG)	1014:1053	In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean.
29437916	4	50	dep	clinical	611:618	arg1	handles					637:643	handles	637:643	handles	637:643	With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes.
29437916	8	51	located	observed	1133:1140	arg2	This					1119:1122	This	1119:1122	This	1119:1122	This was only observed in patients with GMPPB in our large dystroglycanopathy cohort.
29437916	8	51	located	observed	1133:1140	arg1	cohort					1197:1202	our large dystroglycanopathy cohort	1168:1202	our large dystroglycanopathy cohort	1168:1202	This was only observed in patients with GMPPB in our large dystroglycanopathy cohort.
29437916	8	51	located	observed	1133:1140	arg1	patients					1145:1152	patients	1145:1152	patients with GMPPB	1145:1163	This was only observed in patients with GMPPB in our large dystroglycanopathy cohort.
29437916	4	52	theme	sequential	677:686	arg1	analysis					688:695	parallel or sequential analysis	665:695	parallel or sequential analysis of all known genes	665:714	With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes.
29437916	6	53	from	knowledge	904:912	arg1	features					941:948	clinical and muscle MRI features	917:948	features	941:948	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	4	54	theme	genes	710:714	arg1	analysis					688:695	parallel or sequential analysis	665:695	parallel or sequential analysis of all known genes	665:714	With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes.
29437916	10	55	with	patients	1411:1418	arg1	dystroglycanopathy					1425:1442	dystroglycanopathy	1425:1442	dystroglycanopathy	1425:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	2	56	from	glycoepitopes	422:434	arg1	biopsy					456:461	a muscle biopsy	447:461	a muscle biopsy	447:461	Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy.
29437916	2	57	theme	immunoreactivity	378:393	arg1	reduction					365:373	variable reduction	356:373	variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy	356:461	Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy.
29437916	5	58	theme	clinical	737:744	arg1	findings					771:778	clinical, genetic and biochemical findings	737:778	clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy	737:834	METHODS We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy.
29437916	7	59	theme	blot	1066:1069	arg1	analysis					1071:1078	Western blot analysis	1058:1078	Western blot analysis of all patients analysed by this mean	1058:1116	In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean.
29437916	6	60	theme	clinical	917:924	arg1	features					941:948	clinical and muscle MRI features	917:948	features	941:948	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	1	61	from	Defects	101:107	arg1	glycosylation					112:124	glycosylation	112:124	glycosylation of alpha-dystroglycan (α-DG)	112:153	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	1	62	with	disorders	181:189	arg1	heterogeneity					222:234	wide clinical and genetic heterogeneity	196:234	wide clinical and genetic heterogeneity	196:234	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	6	63	theme	current	896:902	arg1	knowledge					904:912	current knowledge	896:912	current knowledge on clinical and muscle MRI features of this condition	896:966	RESULTS We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition.
29437916	10	64	from	mobility	1399:1406	arg1	patients					1411:1418	patients	1411:1418	patients with dystroglycanopathy	1411:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	9	65	from	shift	1247:1251	arg1	patients					1256:1263	patients	1256:1263	patients with GMPPB	1256:1274	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	1	66	theme	alpha-dystroglycan	129:146	arg1	glycosylation					112:124	glycosylation	112:124	glycosylation of alpha-dystroglycan (α-DG)	112:153	BACKGROUND Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies.
29437916	9	67	link	N-linked	1296:1303	arg1	glycosylation					1305:1317	abnormal N-linked glycosylation	1287:1317	abnormal N-linked glycosylation of β-DG	1287:1325	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	8	68	theme	dystroglycanopathy	1178:1195	arg1	cohort					1197:1202	our large dystroglycanopathy cohort	1168:1202	our large dystroglycanopathy cohort	1168:1202	This was only observed in patients with GMPPB in our large dystroglycanopathy cohort.
29437916	9	69	theme	abnormal	1287:1294	arg1	glycosylation					1305:1317	abnormal N-linked glycosylation	1287:1317	abnormal N-linked glycosylation of β-DG	1287:1325	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	7	70	theme	beta-dystroglycan	1030:1046	arg1	mobility					1018:1025	the mobility	1014:1025	the mobility of beta-dystroglycan (β-DG)	1014:1053	In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean.
29437916	2	71	theme	variable	356:363	arg1	reduction					365:373	variable reduction	356:373	variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy	356:461	Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy.
29437916	3	72	theme	diphosphate	517:527	arg1	GMPPB					558:562	GMPPB	558:562	GMPPB	558:562	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	3	72	theme	diphosphate	517:527	arg1	B					555:555	guanosine diphosphate mannose pyrophosphorylase B	507:555	guanosine diphosphate mannose pyrophosphorylase B (GMPPB)	507:563	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	0	73	theme	gene-related	57:68	arg1	dystrophy					79:87	GMPPB gene-related muscular dystrophy	51:87	GMPPB gene-related muscular dystrophy	51:87	Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.
29437916	9	74	theme	N-linked	1296:1303	arg1	glycosylation					1305:1317	abnormal N-linked glycosylation	1287:1317	abnormal N-linked glycosylation of β-DG	1287:1325	We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of β-DG.
29437916	0	75	dep	shift	9:13	arg1	marker					41:46	a marker	39:46	a marker of GMPPB gene-related muscular dystrophy	39:87	Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.
29437916	3	76	from	mutations	474:482	arg1	B					555:555	guanosine diphosphate mannose pyrophosphorylase B	507:555	guanosine diphosphate mannose pyrophosphorylase B (GMPPB)	507:563	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	3	76	from	mutations	474:482	arg1	genes					490:494	18 genes	487:494	18 genes	487:494	Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date.
29437916	0	77	theme	GMPPB	51:55	arg1	dystrophy					79:87	GMPPB gene-related muscular dystrophy	51:87	GMPPB gene-related muscular dystrophy	51:87	Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.
29437916	7	78	theme	patients	1087:1094	arg1	analysis					1071:1078	Western blot analysis	1058:1078	Western blot analysis of all patients analysed by this mean	1058:1116	In addition, we report a consistent shift in the mobility of beta-dystroglycan (β-DG) on Western blot analysis of all patients analysed by this mean.
29437916	10	79	theme	electrophoretic	1383:1397	arg1	mobility					1399:1406	β-DG electrophoretic mobility	1378:1406	β-DG electrophoretic mobility in patients with dystroglycanopathy	1378:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	2	80	theme	specific	409:416	arg1	antibodies					398:407	antibodies	398:407	antibodies specific for glycoepitopes of α-DG on a muscle biopsy	398:461	Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy.
29437916	8	81	with	patients	1145:1152	arg1	GMPPB					1159:1163	GMPPB	1159:1163	GMPPB	1159:1163	This was only observed in patients with GMPPB in our large dystroglycanopathy cohort.
29437916	10	82	from	GMPPB	1495:1499	arg1	change					1368:1373	a change	1366:1373	a change in β-DG electrophoretic mobility in patients with dystroglycanopathy	1366:1442	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29437916	10	82	from	GMPPB	1495:1499	arg1	marker					1461:1466	a distinctive marker	1447:1466	a distinctive marker of the molecular defect in GMPPB	1447:1499	CONCLUSIONS Our data demonstrate that a change in β-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.
29377347	6	0	theme	cells	867:871	arg1	migration					850:858	migration	850:858	migration of HCC cells	850:871	Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT).
29377347	10	1	theme	CD44s	1417:1421	arg1	cells					1433:1437	CD44s knockdown cells	1417:1437	CD44s knockdown cells	1417:1437	The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively.
29377347	11	2	theme	inhibitor	1497:1505	arg1	U0126					1507:1511	The MEK/ERK inhibitor U0126	1485:1511	The MEK/ERK inhibitor U0126	1485:1511	The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells.
29377347	1	3	theme	exact	233:237	arg1	inhibitor					187:195	an N-linked glycosylation (NLG) inhibitor	155:195	an N-linked glycosylation (NLG) inhibitor with strong antitumor activity	155:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	1	3	theme	exact	233:237	arg1	mechanism					260:268	the exact underlying molecular mechanism	229:268	the exact underlying molecular mechanism of which remains to be elucidated	229:302	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	9	4	theme	HCC	1252:1254	arg1	cells					1256:1260	HCC cells	1252:1260	HCC cells	1252:1260	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	6	5	theme	HCC	863:865	arg1	cells					867:871	HCC cells	863:871	HCC cells	863:871	Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT).
29377347	5	6	theme	cells	752:756	arg1	proliferation					731:743	proliferation	731:743	proliferation of HCC cells	731:756	TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase.
29377347	12	7	theme	growth	1632:1637	arg1	beta					1646:1649	exogenous transforming growth factor beta	1609:1649	exogenous transforming growth factor beta	1609:1649	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	1	8	theme	underlying	239:248	arg1	inhibitor					187:195	an N-linked glycosylation (NLG) inhibitor	155:195	an N-linked glycosylation (NLG) inhibitor with strong antitumor activity	155:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	1	8	theme	underlying	239:248	arg1	mechanism					260:268	the exact underlying molecular mechanism	229:268	the exact underlying molecular mechanism of which remains to be elucidated	229:302	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	8	9	from	prognosis	1133:1141	arg1	patients					1150:1157	HCC patients	1146:1157	HCC patients	1146:1157	In addition, CD44s is involved in promoting EMT and is associated with a poor prognosis in HCC patients.
29377347	12	10	dep	-mediated	1658:1666	arg1	beta					1646:1649	exogenous transforming growth factor beta	1609:1649	exogenous transforming growth factor beta	1609:1649	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	10	11	theme	cell	1361:1364	arg1	migration					1366:1374	cell migration	1361:1374	cell migration	1361:1374	The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively.
29377347	3	12	theme	HCC	504:506	arg1	proliferation					513:525	HCC cell proliferation	504:525	HCC cell proliferation	504:525	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	1	13	theme	molecular	250:258	arg1	inhibitor					187:195	an N-linked glycosylation (NLG) inhibitor	155:195	an N-linked glycosylation (NLG) inhibitor with strong antitumor activity	155:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	1	13	theme	molecular	250:258	arg1	mechanism					260:268	the exact underlying molecular mechanism	229:268	the exact underlying molecular mechanism of which remains to be elucidated	229:302	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	0	14	theme	CD44s	105:109	arg1	suppression					90:100	suppression	90:100	suppression of CD44s	90:109	Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
29377347	0	14	theme	CD44s	105:109	arg1	pathway					126:132	the ERK1/2 pathway	115:132	the ERK1/2 pathway	115:132	Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
29377347	3	15	from	effects	487:493	arg1	migration					531:539	migration	531:539	migration	531:539	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	3	15	from	effects	487:493	arg1	proliferation					513:525	HCC cell proliferation	504:525	HCC cell proliferation	504:525	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	3	16	theme	cell	508:511	arg1	proliferation					513:525	HCC cell proliferation	504:525	HCC cell proliferation	504:525	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	13	17	theme	HCC	1845:1847	arg1	cells					1849:1853	HCC cells	1845:1853	HCC cells	1845:1853	In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
29377347	0	18	theme	ERK1/2	119:124	arg1	pathway					126:132	the ERK1/2 pathway	115:132	the ERK1/2 pathway	115:132	Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
29377347	8	19	theme	poor	1128:1131	arg1	prognosis					1133:1141	a poor prognosis	1126:1141	a poor prognosis in HCC patients	1126:1157	In addition, CD44s is involved in promoting EMT and is associated with a poor prognosis in HCC patients.
29377347	12	20	theme	-mediated	1658:1666	arg1	EMT					1668:1670	exogenous transforming growth factor beta (TGF-β)-mediated EMT	1609:1670	exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism	1609:1703	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	3	21	theme	TM	498:499	arg1	mechanism					556:564	the mechanism	552:564	the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects	483:581	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	3	21	theme	TM	498:499	arg1	effects					487:493	the effects	483:493	the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects	483:581	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	8	22	theme	HCC	1146:1148	arg1	patients					1150:1157	HCC patients	1146:1157	HCC patients	1146:1157	In addition, CD44s is involved in promoting EMT and is associated with a poor prognosis in HCC patients.
29377347	1	23	theme	N-linked	158:165	arg1	NLG					182:184	NLG	182:184	NLG	182:184	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	1	23	theme	N-linked	158:165	arg1	glycosylation					167:179	N-linked glycosylation	158:179	an N-linked glycosylation (NLG) inhibitor with strong antitumor activity	155:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	0	24	from	migration	44:52	arg1	carcinoma					72:80	hepatocellular carcinoma	57:80	hepatocellular carcinoma	57:80	Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
29377347	11	25	theme	cell	1554:1557	arg1	migration					1559:1567	hyaluronic acid-induced cell migration	1530:1567	hyaluronic acid-induced cell migration	1530:1567	The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells.
29377347	9	26	from	phosphorylation	1223:1237	arg1	cells					1256:1260	HCC cells	1252:1260	HCC cells	1252:1260	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	1	27	theme	glycosylation	167:179	arg1	Tunicamycin					135:145	Tunicamycin	135:145	Tunicamycin (TM)	135:150	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	1	27	theme	glycosylation	167:179	arg1	inhibitor					187:195	an N-linked glycosylation (NLG) inhibitor	155:195	an N-linked glycosylation (NLG) inhibitor with strong antitumor activity	155:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	1	27	theme	glycosylation	167:179	arg1	mechanism					260:268	the exact underlying molecular mechanism	229:268	the exact underlying molecular mechanism of which remains to be elucidated	229:302	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	2	28	theme	hepatocellular	428:441	arg1	HCC					455:457	HCC	455:457	HCC	455:457	In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC).
29377347	2	28	theme	hepatocellular	428:441	arg1	carcinomas					443:452	hepatocellular carcinomas	428:452	hepatocellular carcinomas (HCC)	428:458	In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC).
29377347	9	29	theme	CD44s	1284:1288	arg1	migration					1321:1329	CD44s overexpression-associated cell migration	1284:1329	CD44s overexpression-associated cell migration	1284:1329	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	1	30	link	N-linked	158:165	arg1	NLG					182:184	NLG	182:184	NLG	182:184	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	1	30	link	N-linked	158:165	arg1	glycosylation					167:179	N-linked glycosylation	158:179	an N-linked glycosylation (NLG) inhibitor with strong antitumor activity	155:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	4	31	theme	carcinoma	701:709	arg1	cells					711:715	hepatocellular carcinoma cells	686:715	hepatocellular carcinoma cells	686:715	Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells.
29377347	2	32	theme	drug	356:359	arg1	resistance					361:370	drug resistance	356:370	drug resistance	356:370	In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC).
29377347	9	33	theme	overexpression-associated	1290:1314	arg1	migration					1321:1329	CD44s overexpression-associated cell migration	1284:1329	CD44s overexpression-associated cell migration	1284:1329	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	10	34	theme	knockdown	1423:1431	arg1	cells					1433:1437	CD44s knockdown cells	1417:1437	CD44s knockdown cells	1417:1437	The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively.
29377347	11	35	theme	hyaluronic	1530:1539	arg1	migration					1559:1567	hyaluronic acid-induced cell migration	1530:1567	hyaluronic acid-induced cell migration	1530:1567	The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells.
29377347	4	36	theme	hepatocellular	686:699	arg1	cells					711:715	hepatocellular carcinoma cells	686:715	hepatocellular carcinoma cells	686:715	Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells.
29377347	12	37	theme	transforming	1619:1630	arg1	beta					1646:1649	exogenous transforming growth factor beta	1609:1649	exogenous transforming growth factor beta	1609:1649	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	4	38	theme	cell	621:624	arg1	proliferation					626:638	cell proliferation	621:638	cell proliferation	621:638	Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells.
29377347	2	39	theme	treatments	413:422	arg1	efficacy					389:396	the efficacy	385:396	the efficacy of combination treatments for hepatocellular carcinomas (HCC)	385:458	In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC).
29377347	9	40	theme	cell	1316:1319	arg1	migration					1321:1329	CD44s overexpression-associated cell migration	1284:1329	CD44s overexpression-associated cell migration	1284:1329	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	9	41	theme	CD44s	1178:1182	arg1	Overexpression					1160:1173	Overexpression	1160:1173	Overexpression of CD44s	1160:1182	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	12	42	theme	exogenous	1609:1617	arg1	beta					1646:1649	exogenous transforming growth factor beta	1609:1649	exogenous transforming growth factor beta	1609:1649	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	5	43	theme	cycle	794:798	arg1	arrest					800:805	cell cycle arrest	789:805	cell cycle arrest	789:805	TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase.
29377347	2	44	theme	combination	401:411	arg1	treatments					413:422	combination treatments	401:422	combination treatments	401:422	In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC).
29377347	13	45	theme	CD44s	1877:1881	arg1	pathway					1908:1914	the ERK1/2 signaling pathway	1887:1914	the ERK1/2 signaling pathway	1887:1914	In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
29377347	13	45	theme	CD44s	1877:1881	arg1	inhibition					1863:1872	inhibition	1863:1872	inhibition of CD44s	1863:1881	In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
29377347	4	46	theme	cells	711:715	arg1	apoptosis					673:681	induced apoptosis	665:681	induced apoptosis of hepatocellular carcinoma cells	665:715	Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells.
29377347	4	46	theme	cells	711:715	arg1	migration					644:652	migration	644:652	migration	644:652	Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells.
29377347	4	46	theme	cells	711:715	arg1	proliferation					626:638	cell proliferation	621:638	cell proliferation	621:638	Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells.
29377347	12	47	theme	factor	1639:1644	arg1	beta					1646:1649	exogenous transforming growth factor beta	1609:1649	exogenous transforming growth factor beta	1609:1649	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	5	48	theme	HCC	748:750	arg1	cells					752:756	HCC cells	748:756	HCC cells	748:756	TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase.
29377347	13	49	theme	cells	1849:1853	arg1	migration					1832:1840	migration	1832:1840	migration	1832:1840	In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
29377347	13	49	theme	cells	1849:1853	arg1	proliferation					1814:1826	proliferation	1814:1826	proliferation	1814:1826	In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
29377347	9	50	theme	tumor	1193:1197	arg1	migration					1199:1207	tumor migration	1193:1207	tumor migration	1193:1207	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	3	51	from	mechanism	556:564	arg1	migration					531:539	migration	531:539	migration	531:539	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	3	51	from	mechanism	556:564	arg1	proliferation					513:525	HCC cell proliferation	504:525	HCC cell proliferation	504:525	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	5	52	theme	G2/M	814:817	arg1	phase					819:823	the G2/M phase	810:823	the G2/M phase	810:823	TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase.
29377347	1	53	with	inhibitor	187:195	arg1	activity					219:226	strong antitumor activity	202:226	strong antitumor activity	202:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	7	54	theme	HCC	983:985	arg1	cells					987:991	HCC cells	983:991	HCC cells	983:991	TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation.
29377347	1	55	theme	strong	202:207	arg1	activity					219:226	strong antitumor activity	202:226	strong antitumor activity	202:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	0	56	theme	hepatocellular	57:70	arg1	carcinoma					72:80	hepatocellular carcinoma	57:80	hepatocellular carcinoma	57:80	Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
29377347	6	57	theme	epithelial-mesenchymal	903:924	arg1	EMT					938:940	EMT	938:940	EMT	938:940	Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT).
29377347	6	57	theme	epithelial-mesenchymal	903:924	arg1	transition					926:935	CD44s-mediated epithelial-mesenchymal transition	888:935	CD44s-mediated epithelial-mesenchymal transition (EMT)	888:941	Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT).
29377347	7	58	theme	CD44	1007:1010	arg1	expression					1012:1021	CD44 expression	1007:1021	CD44 expression	1007:1021	TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation.
29377347	7	59	theme	cells	987:991	arg1	migration					957:965	migration	957:965	migration	957:965	TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation.
29377347	7	59	theme	cells	987:991	arg1	invasion					971:978	invasion	971:978	invasion	971:978	TM inhibited migration and invasion of HCC cells by decreasing CD44 expression and altering its glycosylation.
29377347	4	60	theme	induced	665:671	arg1	apoptosis					673:681	induced apoptosis	665:681	induced apoptosis of hepatocellular carcinoma cells	665:715	Our results showed that TM inhibited cell proliferation and migration as well as induced apoptosis of hepatocellular carcinoma cells.
29377347	6	61	theme	CD44s-mediated	888:901	arg1	EMT					938:940	EMT	938:940	EMT	938:940	Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT).
29377347	6	61	theme	CD44s-mediated	888:901	arg1	transition					926:935	CD44s-mediated epithelial-mesenchymal transition	888:935	CD44s-mediated epithelial-mesenchymal transition (EMT)	888:941	Meanwhile, TM inhibited migration of HCC cells by suppressing CD44s-mediated epithelial-mesenchymal transition (EMT).
29377347	13	62	theme	ERK1/2	1891:1896	arg1	pathway					1908:1914	the ERK1/2 signaling pathway	1887:1914	the ERK1/2 signaling pathway	1887:1914	In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
29377347	11	63	theme	acid-induced	1541:1552	arg1	migration					1559:1567	hyaluronic acid-induced cell migration	1530:1567	hyaluronic acid-induced cell migration	1530:1567	The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells.
29377347	12	64	theme	TGF-β-mediated	1722:1735	arg1	loss					1737:1740	the TGF-β-mediated loss	1718:1740	the TGF-β-mediated loss of E-cadherin	1718:1754	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	3	65	theme	effects	575:581	arg1	mechanism					556:564	the mechanism	552:564	the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects	483:581	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	3	65	theme	effects	575:581	arg1	effects					487:493	the effects	483:493	the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects	483:581	Here, we investigated the effects of TM on HCC cell proliferation and migration as well as the mechanism of those effects.
29377347	11	66	theme	HCC	1572:1574	arg1	cells					1576:1580	HCC cells	1572:1580	HCC cells	1572:1580	The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells.
29377347	2	67	theme	previous	312:319	arg1	studies					321:327	our previous studies	308:327	our previous studies	308:327	In our previous studies, we found that TM reversed drug resistance and improved the efficacy of combination treatments for hepatocellular carcinomas (HCC).
29377347	12	68	theme	ERK1/2-dependent	1678:1693	arg1	mechanism					1695:1703	an ERK1/2-dependent mechanism	1675:1703	an ERK1/2-dependent mechanism	1675:1703	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	1	69	theme	antitumor	209:217	arg1	activity					219:226	strong antitumor activity	202:226	strong antitumor activity	202:226	Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong antitumor activity, the exact underlying molecular mechanism of which remains to be elucidated.
29377347	5	70	theme	cell	789:792	arg1	arrest					800:805	cell cycle arrest	789:805	cell cycle arrest	789:805	TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase.
29377347	10	71	theme	TM	1347:1348	arg1	ability					1336:1342	The ability	1332:1342	The ability of TM to inhibit cell migration and invasion	1332:1387	The ability of TM to inhibit cell migration and invasion was enhanced or reversed in CD44s knockdown cells and cells overexpressing CD44s, respectively.
29377347	9	72	theme	ERK1/2	1242:1247	arg1	phosphorylation					1223:1237	phosphorylation	1223:1237	phosphorylation of ERK1/2 in HCC cells	1223:1260	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	12	73	theme	E-cadherin	1745:1754	arg1	loss					1737:1740	the TGF-β-mediated loss	1718:1740	the TGF-β-mediated loss of E-cadherin	1718:1754	Furthermore, TM inhibited exogenous transforming growth factor beta (TGF-β)-mediated EMT by an ERK1/2-dependent mechanism and restored the TGF-β-mediated loss of E-cadherin.
29377347	13	74	theme	signaling	1898:1906	arg1	pathway					1908:1914	the ERK1/2 signaling pathway	1887:1914	the ERK1/2 signaling pathway	1887:1914	In summary, our study provides evidence that TM inhibits proliferation and migration of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.
29377347	9	75	dep	promoted	1184:1191	arg1	whereas					1263:1269	whereas	1263:1269	whereas	1263:1269	Overexpression of CD44s promoted tumor migration and activated phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression-associated cell migration.
29377347	0	76	from	proliferation	26:38	arg1	carcinoma					72:80	hepatocellular carcinoma	57:80	hepatocellular carcinoma	57:80	Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
29377347	0	77	theme	cell	21:24	arg1	proliferation					26:38	cell proliferation	21:38	cell proliferation	21:38	Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma through suppression of CD44s and the ERK1/2 pathway.
29377347	5	78	theme	cell	770:773	arg1	apoptosis					775:783	cell apoptosis	770:783	cell apoptosis	770:783	TM inhibited proliferation of HCC cells by inducing cell apoptosis and cell cycle arrest at the G2/M phase.
29377347	11	79	theme	MEK/ERK	1489:1495	arg1	U0126					1507:1511	The MEK/ERK inhibitor U0126	1485:1511	The MEK/ERK inhibitor U0126	1485:1511	The MEK/ERK inhibitor U0126 and TM inhibited hyaluronic acid-induced cell migration in HCC cells.
31661879	0	0	theme	Computational	107:119	arg1	Approach					138:145	an Integrative Computational and Experimental Approach	92:145	an Integrative Computational and Experimental Approach	92:145	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	5	1	theme	human	759:763	arg1	DHDDS					765:769	the full-length human DHDDS	743:769	the full-length human DHDDS using a multidisciplinary experimental and computational approach	743:835	Here, we provide a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach.
31661879	3	2	theme	conserved	564:572	arg1	domains					574:580	any known conserved domains	554:580	any known conserved domains	554:580	Importantly, DHDDS encompasses a C-terminal region, which does not converge with any known conserved domains.
31661879	7	3	theme	catalytic	1010:1018	arg1	activity					1020:1027	catalytic activity	1010:1027	catalytic activity	1010:1027	Enzyme kinetics assays revealed that it exhibits catalytic activity, although reduced compared to that reported for the intact heteromeric complex.
31661879	1	4	theme	carrier	300:306	arg1	precursor					308:316	the glycosyl carrier precursor	287:316	the glycosyl carrier precursor for N-linked protein glycosylation	287:351	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	0	5	theme	Integrative	95:105	arg1	Approach					138:145	an Integrative Computational and Experimental Approach	92:145	an Integrative Computational and Experimental Approach	92:145	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	6	6	theme	monodisperse	925:936	arg1	homodimer					938:946	a monodisperse homodimer	923:946	a monodisperse homodimer in solution	923:958	Size-exclusion chromatography multi-angle light scattering revealed that DHDDS forms a monodisperse homodimer in solution.
31661879	2	7	from	role	384:387	arg1	biogenesis					419:428	protein biogenesis	411:428	protein biogenesis	411:428	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	0	8	theme	Experimental	125:136	arg1	Approach					138:145	an Integrative Computational and Experimental Approach	92:145	an Integrative Computational and Experimental Approach	92:145	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	5	9	theme	structural	722:731	arg1	model					733:737	a structural model	720:737	a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach	720:835	Here, we provide a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach.
31661879	1	10	link	N-linked	322:329	arg1	glycosylation					339:351	N-linked protein glycosylation	322:351	N-linked protein glycosylation	322:351	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	8	11	theme	helix-turn-helix	1162:1177	arg1	motif					1179:1183	a helix-turn-helix motif	1160:1183	a helix-turn-helix motif	1160:1183	Our model suggests that the DHDDS C-terminus forms a helix-turn-helix motif, tightly packed against the core catalytic domain.
31661879	11	12	theme	functional	1676:1685	arg1	studies					1687:1693	future structural and functional studies	1654:1693	future structural and functional studies of the complex	1654:1708	Finally, we provide a model for the DHDDS-NgBR heterodimer, offering a structural framework for future structural and functional studies of the complex.
31661879	10	13	theme	folded	1544:1549	arg1	state					1551:1555	its overall folded state	1532:1555	its overall folded state	1532:1555	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	10	14	theme	time-dependent	1458:1471	arg1	uptake					1483:1488	time-dependent deuterium uptake	1458:1488	time-dependent deuterium uptake	1458:1488	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	1	15	theme	N-linked	322:329	arg1	glycosylation					339:351	N-linked protein glycosylation	322:351	N-linked protein glycosylation	322:351	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	5	16	theme	computational	814:826	arg1	approach					828:835	a multidisciplinary experimental and computational approach	777:835	a multidisciplinary experimental and computational approach	777:835	Here, we provide a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach.
31661879	2	17	theme	protein	411:417	arg1	biogenesis					419:428	protein biogenesis	411:428	protein biogenesis	411:428	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	6	18	from	homodimer	938:946	arg1	solution					951:958	solution	951:958	solution	951:958	Size-exclusion chromatography multi-angle light scattering revealed that DHDDS forms a monodisperse homodimer in solution.
31661879	9	19	theme	full-length	1321:1331	arg1	DHDDS					1333:1337	the full-length DHDDS	1317:1337	the full-length DHDDS	1317:1337	This model is consistent with small-angle X-ray scattering data, indicating that the full-length DHDDS maintains a similar conformation in solution.
31661879	1	20	theme	catalytic	200:208	arg1	synthase					176:183	Dehydrodolichyl diphosphate synthase	148:183	Dehydrodolichyl diphosphate synthase (DHDDS)	148:191	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	1	20	theme	catalytic	200:208	arg1	subunit					210:216	the catalytic subunit	196:216	the catalytic subunit of the heteromeric human cis-prenyltransferase complex	196:271	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	9	21	with	consistent	1250:1259	arg1	data					1295:1298	small-angle X-ray scattering data	1266:1298	small-angle X-ray scattering data	1266:1298	This model is consistent with small-angle X-ray scattering data, indicating that the full-length DHDDS maintains a similar conformation in solution.
31661879	7	22	theme	Enzyme	961:966	arg1	assays					977:982	Enzyme kinetics assays	961:982	Enzyme kinetics assays	961:982	Enzyme kinetics assays revealed that it exhibits catalytic activity, although reduced compared to that reported for the intact heteromeric complex.
31661879	2	23	theme	human	457:461	arg1	diseases					463:470	human diseases	457:470	human diseases	457:470	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	4	24	theme	DHDDS	629:633	arg1	importance					615:624	the clinical importance	602:624	the clinical importance of DHDDS	602:633	Therefore, despite the clinical importance of DHDDS, our understating of its structure-function relations remains poor.
31661879	7	25	theme	kinetics	968:975	arg1	assays					977:982	Enzyme kinetics assays	961:982	Enzyme kinetics assays	961:982	Enzyme kinetics assays revealed that it exhibits catalytic activity, although reduced compared to that reported for the intact heteromeric complex.
31661879	0	26	theme	Structural	0:9	arg1	Characterization					11:26	Structural Characterization	0:26	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase	0:84	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	1	27	theme	protein	331:337	arg1	glycosylation					339:351	N-linked protein glycosylation	322:351	N-linked protein glycosylation	322:351	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	8	28	theme	DHDDS	1137:1141	arg1	C-terminus					1143:1152	the DHDDS C-terminus	1133:1152	the DHDDS C-terminus	1133:1152	Our model suggests that the DHDDS C-terminus forms a helix-turn-helix motif, tightly packed against the core catalytic domain.
31661879	2	29	theme	important	374:382	arg1	role					384:387	the important role	370:387	the important role of N-glycosylation in protein biogenesis	370:428	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	11	30	theme	DHDDS-NgBR	1594:1603	arg1	heterodimer					1605:1615	the DHDDS-NgBR heterodimer	1590:1615	the DHDDS-NgBR heterodimer	1590:1615	Finally, we provide a model for the DHDDS-NgBR heterodimer, offering a structural framework for future structural and functional studies of the complex.
31661879	0	31	theme	Full-Length	31:41	arg1	Synthase					77:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	6	32	theme	light	880:884	arg1	scattering					886:895	Size-exclusion chromatography multi-angle light scattering	838:895	Size-exclusion chromatography multi-angle light scattering	838:895	Size-exclusion chromatography multi-angle light scattering revealed that DHDDS forms a monodisperse homodimer in solution.
31661879	7	33	theme	intact	1081:1086	arg1	complex					1100:1106	the intact heteromeric complex	1077:1106	the intact heteromeric complex	1077:1106	Enzyme kinetics assays revealed that it exhibits catalytic activity, although reduced compared to that reported for the intact heteromeric complex.
31661879	1	34	theme	heteromeric	225:235	arg1	complex					265:271	the heteromeric human cis-prenyltransferase complex	221:271	the heteromeric human cis-prenyltransferase complex	221:271	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	10	35	theme	C-terminal	1497:1506	arg1	domain					1508:1513	the C-terminal domain	1493:1513	the C-terminal domain	1493:1513	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	1	36	theme	human	237:241	arg1	complex					265:271	the heteromeric human cis-prenyltransferase complex	221:271	the heteromeric human cis-prenyltransferase complex	221:271	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	0	37	theme	Dehydrodolichyl	49:63	arg1	Synthase					77:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	3	38	theme	known	558:562	arg1	domains					574:580	any known conserved domains	554:580	any known conserved domains	554:580	Importantly, DHDDS encompasses a C-terminal region, which does not converge with any known conserved domains.
31661879	8	39	theme	catalytic	1218:1226	arg1	domain					1228:1233	the core catalytic domain	1209:1233	the core catalytic domain	1209:1233	Our model suggests that the DHDDS C-terminus forms a helix-turn-helix motif, tightly packed against the core catalytic domain.
31661879	10	40	theme	deuterium	1473:1481	arg1	uptake					1483:1488	time-dependent deuterium uptake	1458:1488	time-dependent deuterium uptake	1458:1488	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	1	41	theme	cis-prenyltransferase	243:263	arg1	complex					265:271	the heteromeric human cis-prenyltransferase complex	221:271	the heteromeric human cis-prenyltransferase complex	221:271	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	0	42	theme	Human	43:47	arg1	Synthase					77:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	5	43	theme	multidisciplinary	779:795	arg1	approach					828:835	a multidisciplinary experimental and computational approach	777:835	a multidisciplinary experimental and computational approach	777:835	Here, we provide a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach.
31661879	10	44	theme	hydrogen-deuterium	1395:1412	arg1	experiments					1441:1451	hydrogen-deuterium exchange mass-spectrometry experiments	1395:1451	hydrogen-deuterium exchange mass-spectrometry experiments	1395:1451	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	10	45	with	consistent	1516:1525	arg1	state					1551:1555	its overall folded state	1532:1555	its overall folded state	1532:1555	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	6	46	theme	multi-angle	868:878	arg1	scattering					886:895	Size-exclusion chromatography multi-angle light scattering	838:895	Size-exclusion chromatography multi-angle light scattering	838:895	Size-exclusion chromatography multi-angle light scattering revealed that DHDDS forms a monodisperse homodimer in solution.
31661879	1	47	theme	complex	265:271	arg1	synthase					176:183	Dehydrodolichyl diphosphate synthase	148:183	Dehydrodolichyl diphosphate synthase (DHDDS)	148:191	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	1	47	theme	complex	265:271	arg1	subunit					210:216	the catalytic subunit	196:216	the catalytic subunit of the heteromeric human cis-prenyltransferase complex	196:271	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	0	48	theme	Synthase	77:84	arg1	Characterization					11:26	Structural Characterization	0:26	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase	0:84	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	5	49	theme	experimental	797:808	arg1	approach					828:835	a multidisciplinary experimental and computational approach	777:835	a multidisciplinary experimental and computational approach	777:835	Here, we provide a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach.
31661879	3	50	theme	C-terminal	506:515	arg1	region					517:522	a C-terminal region	504:522	a C-terminal region	504:522	Importantly, DHDDS encompasses a C-terminal region, which does not converge with any known conserved domains.
31661879	6	51	theme	chromatography	853:866	arg1	scattering					886:895	Size-exclusion chromatography multi-angle light scattering	838:895	Size-exclusion chromatography multi-angle light scattering	838:895	Size-exclusion chromatography multi-angle light scattering revealed that DHDDS forms a monodisperse homodimer in solution.
31661879	1	52	theme	Dehydrodolichyl	148:162	arg1	synthase					176:183	Dehydrodolichyl diphosphate synthase	148:183	Dehydrodolichyl diphosphate synthase (DHDDS)	148:191	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	1	52	theme	Dehydrodolichyl	148:162	arg1	subunit					210:216	the catalytic subunit	196:216	the catalytic subunit of the heteromeric human cis-prenyltransferase complex	196:271	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	1	52	theme	Dehydrodolichyl	148:162	arg1	DHDDS					186:190	DHDDS	186:190	DHDDS	186:190	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	0	53	theme	Diphosphate	65:75	arg1	Synthase					77:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Full-Length Human Dehydrodolichyl Diphosphate Synthase	31:84	Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.
31661879	4	54	theme	clinical	606:613	arg1	importance					615:624	the clinical importance	602:624	the clinical importance of DHDDS	602:633	Therefore, despite the clinical importance of DHDDS, our understating of its structure-function relations remains poor.
31661879	9	55	theme	small-angle	1266:1276	arg1	scattering					1284:1293	small-angle X-ray scattering	1266:1293	small-angle X-ray scattering data	1266:1298	This model is consistent with small-angle X-ray scattering data, indicating that the full-length DHDDS maintains a similar conformation in solution.
31661879	6	56	theme	Size-exclusion	838:851	arg1	chromatography					853:866	Size-exclusion chromatography	838:866	Size-exclusion chromatography multi-angle light scattering	838:895	Size-exclusion chromatography multi-angle light scattering revealed that DHDDS forms a monodisperse homodimer in solution.
31661879	1	57	theme	diphosphate	164:174	arg1	synthase					176:183	Dehydrodolichyl diphosphate synthase	148:183	Dehydrodolichyl diphosphate synthase (DHDDS)	148:191	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	1	57	theme	diphosphate	164:174	arg1	subunit					210:216	the catalytic subunit	196:216	the catalytic subunit of the heteromeric human cis-prenyltransferase complex	196:271	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	1	57	theme	diphosphate	164:174	arg1	DHDDS					186:190	DHDDS	186:190	DHDDS	186:190	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31661879	11	58	theme	future	1654:1659	arg1	studies					1687:1693	future structural and functional studies	1654:1693	future structural and functional studies of the complex	1654:1708	Finally, we provide a model for the DHDDS-NgBR heterodimer, offering a structural framework for future structural and functional studies of the complex.
31661879	9	59	theme	similar	1351:1357	arg1	conformation					1359:1370	a similar conformation	1349:1370	a similar conformation	1349:1370	This model is consistent with small-angle X-ray scattering data, indicating that the full-length DHDDS maintains a similar conformation in solution.
31661879	5	60	theme	full-length	747:757	arg1	DHDDS					765:769	the full-length human DHDDS	743:769	the full-length human DHDDS using a multidisciplinary experimental and computational approach	743:835	Here, we provide a structural model for the full-length human DHDDS using a multidisciplinary experimental and computational approach.
31661879	7	61	theme	heteromeric	1088:1098	arg1	complex					1100:1106	the intact heteromeric complex	1077:1106	the intact heteromeric complex	1077:1106	Enzyme kinetics assays revealed that it exhibits catalytic activity, although reduced compared to that reported for the intact heteromeric complex.
31661879	2	62	theme	N-glycosylation	392:406	arg1	role					384:387	the important role	370:387	the important role of N-glycosylation in protein biogenesis	370:428	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	10	63	theme	exchange	1414:1421	arg1	experiments					1441:1451	hydrogen-deuterium exchange mass-spectrometry experiments	1395:1451	hydrogen-deuterium exchange mass-spectrometry experiments	1395:1451	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	4	64	theme	relations	679:687	arg1	understating					640:651	our understating	636:651	our understating of its structure-function relations	636:687	Therefore, despite the clinical importance of DHDDS, our understating of its structure-function relations remains poor.
31661879	2	65	gly	N-glycosylation	392:406	arg1	protein					411:417	protein biogenesis	411:428	protein biogenesis	411:428	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	10	66	theme	mass-spectrometry	1423:1439	arg1	experiments					1441:1451	hydrogen-deuterium exchange mass-spectrometry experiments	1395:1451	hydrogen-deuterium exchange mass-spectrometry experiments	1395:1451	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	9	67	theme	X-ray	1278:1282	arg1	scattering					1284:1293	small-angle X-ray scattering	1266:1293	small-angle X-ray scattering data	1266:1298	This model is consistent with small-angle X-ray scattering data, indicating that the full-length DHDDS maintains a similar conformation in solution.
31661879	11	68	theme	structural	1629:1638	arg1	framework					1640:1648	a structural framework	1627:1648	a structural framework for future structural and functional studies of the complex	1627:1708	Finally, we provide a model for the DHDDS-NgBR heterodimer, offering a structural framework for future structural and functional studies of the complex.
31661879	4	69	theme	structure-function	660:677	arg1	relations					679:687	its structure-function relations	656:687	its structure-function relations	656:687	Therefore, despite the clinical importance of DHDDS, our understating of its structure-function relations remains poor.
31661879	11	70	theme	complex	1702:1708	arg1	studies					1687:1693	future structural and functional studies	1654:1693	future structural and functional studies of the complex	1654:1708	Finally, we provide a model for the DHDDS-NgBR heterodimer, offering a structural framework for future structural and functional studies of the complex.
31661879	10	71	theme	overall	1536:1542	arg1	state					1551:1555	its overall folded state	1532:1555	its overall folded state	1532:1555	Moreover, hydrogen-deuterium exchange mass-spectrometry experiments show time-dependent deuterium uptake in the C-terminal domain, consistent with its overall folded state.
31661879	9	72	theme	scattering	1284:1293	arg1	data					1295:1298	small-angle X-ray scattering data	1266:1298	small-angle X-ray scattering data	1266:1298	This model is consistent with small-angle X-ray scattering data, indicating that the full-length DHDDS maintains a similar conformation in solution.
31661879	11	73	theme	structural	1661:1670	arg1	studies					1687:1693	future structural and functional studies	1654:1693	future structural and functional studies of the complex	1654:1708	Finally, we provide a model for the DHDDS-NgBR heterodimer, offering a structural framework for future structural and functional studies of the complex.
31661879	2	74	with	Consistent	354:363	arg1	role					384:387	the important role	370:387	the important role of N-glycosylation in protein biogenesis	370:428	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	2	75	theme	DHDDS	431:435	arg1	mutations					437:445	DHDDS mutations	431:445	DHDDS mutations	431:445	Consistent with the important role of N-glycosylation in protein biogenesis, DHDDS mutations result in human diseases.
31661879	8	76	theme	core	1213:1216	arg1	domain					1228:1233	the core catalytic domain	1209:1233	the core catalytic domain	1209:1233	Our model suggests that the DHDDS C-terminus forms a helix-turn-helix motif, tightly packed against the core catalytic domain.
31661879	1	77	theme	glycosyl	291:298	arg1	precursor					308:316	the glycosyl carrier precursor	287:316	the glycosyl carrier precursor for N-linked protein glycosylation	287:351	Dehydrodolichyl diphosphate synthase (DHDDS) is the catalytic subunit of the heteromeric human cis-prenyltransferase complex, synthesizing the glycosyl carrier precursor for N-linked protein glycosylation.
31481756	4	0	theme	regulation	789:798	arg1	impact					770:775	the impact	766:775	the impact of N40D MOR regulation on synaptic transmission	766:823	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	1	theme	human-induced	650:662	arg1	lines					692:696	seven human-induced pluripotent stem (iPS) cell lines	644:696	seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	644:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	0	2	theme	human	84:88	arg1	neurons					90:96	human neurons	84:96	human neurons	84:96	Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.
31481756	4	3	theme	MOR	785:787	arg1	regulation					789:798	N40D MOR regulation	780:798	N40D MOR regulation	780:798	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	1	4	theme	gene	162:165	arg1	variant					167:173	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant	99:173	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR)	99:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	7	5	link	N-linked	1282:1289	arg1	glycosylation					1291:1303	differential N-linked glycosylation	1269:1303	differential N-linked glycosylation of human MOR N40D	1269:1321	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	4	6	theme	synaptic	803:810	arg1	transmission					812:823	synaptic transmission	803:823	synaptic transmission	803:823	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	6	7	theme	N40D	1200:1203	arg1	iNs					1205:1207	independently engineered isogenic N40D iNs	1166:1207	independently engineered isogenic N40D iNs	1166:1207	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	2	8	from	%	398:398	arg1	Europeans					381:389	Europeans	381:389	Europeans	381:389	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	8	from	%	398:398	arg1	Asians					365:370	Asians	365:370	Asians	365:370	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	8	from	%	398:398	arg1	African-Americans					403:419	African-Americans	403:419	African-Americans	403:419	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	6	9	theme	synaptic	1110:1117	arg1	transmission					1119:1130	synaptic transmission	1110:1130	synaptic transmission	1110:1130	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	6	10	from	effects	1014:1020	arg1	function					1066:1073	neuronal function	1057:1073	neuronal function	1057:1073	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	6	11	theme	background	1025:1034	arg1	variation					1044:1052	background genetic variation	1025:1052	background genetic variation	1025:1052	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	3	12	theme	opioid	427:432	arg1	deaths					448:453	opioid abuse-related deaths	427:453	opioid abuse-related deaths rising at unprecedented rates	427:483	With opioid abuse-related deaths rising at unprecedented rates, understanding these mechanisms may provide a path to therapy.
31481756	7	13	gly	glycosylation	1291:1303	arg1	N40D					1318:1321	human MOR N40D	1308:1321	human MOR N40D	1308:1321	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	4	14	from	subjects	703:710	arg1	lines					692:696	seven human-induced pluripotent stem (iPS) cell lines	644:696	seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	644:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	15	theme	descent	724:730	arg1	subjects					703:710	subjects	703:710	subjects of European descent (both male and female)	703:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	7	16	theme	N-linked	1282:1289	arg1	glycosylation					1291:1303	differential N-linked glycosylation	1269:1303	differential N-linked glycosylation of human MOR N40D	1269:1321	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	4	17	from	impact	770:775	arg1	transmission					812:823	synaptic transmission	803:823	synaptic transmission	803:823	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	6	18	theme	iNs	1205:1207	arg1	iNs					1205:1207	independently engineered isogenic N40D iNs	1166:1207	independently engineered isogenic N40D iNs	1166:1207	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	6	18	theme	iNs	1205:1207	arg1	sets					1158:1161	two sets	1154:1161	two sets of independently engineered isogenic N40D iNs	1154:1207	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	4	19	theme	European	715:722	arg1	descent					724:730	European descent	715:730	European descent	715:730	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	8	20	theme	opioid	1443:1448	arg1	responsivity					1450:1461	altered opioid responsivity	1435:1461	altered opioid responsivity	1435:1461	This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
31481756	4	21	theme	neuronal	618:625	arg1	cells					627:631	induced inhibitory neuronal cells	599:631	induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	599:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	21	theme	neuronal	618:625	arg1	iNs					634:636	iNs	634:636	iNs	634:636	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	22	theme	N40D	780:783	arg1	regulation					789:798	N40D MOR regulation	780:798	N40D MOR regulation	780:798	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	23	from	lines	692:696	arg1	cells					627:631	induced inhibitory neuronal cells	599:631	induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	599:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	23	from	lines	692:696	arg1	iNs					634:636	iNs	634:636	iNs	634:636	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	24	theme	cell	687:690	arg1	lines					692:696	seven human-induced pluripotent stem (iPS) cell lines	644:696	seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	644:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	8	25	theme	individuals	1499:1509	arg1	subset					1489:1494	this subset	1484:1494	this subset of individuals	1484:1509	This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
31481756	6	26	theme	isogenic	1191:1198	arg1	iNs					1205:1207	independently engineered isogenic N40D iNs	1166:1207	independently engineered isogenic N40D iNs	1166:1207	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	5	27	theme	stronger	869:876	arg1	suppression					878:888	consistently stronger suppression	856:888	consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs)	856:958	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	5	27	theme	stronger	869:876	arg1	N40					898:900	N40	898:900	N40	898:900	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	7	28	theme	N40D	1318:1321	arg1	glycosylation					1291:1303	differential N-linked glycosylation	1269:1303	differential N-linked glycosylation of human MOR N40D	1269:1321	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	1	29	theme	N40D	188:191	arg1	receptor					202:209	the N40D µ-opioid receptor	184:209	the N40D µ-opioid receptor (MOR)	184:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	29	theme	N40D	188:191	arg1	MOR					212:214	MOR	212:214	MOR	212:214	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	0	30	theme	mu-opioid	26:34	arg1	receptor					36:43	N40D mu-opioid receptor	21:43	N40D mu-opioid receptor variant	21:51	Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.
31481756	1	31	theme	other	268:272	arg1	drugs					274:278	other drugs	268:278	other drugs	268:278	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	8	32	theme	molecular	1369:1377	arg1	differences					1379:1389	neurophysiological and molecular differences	1346:1389	neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals	1346:1509	This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
31481756	1	33	theme	OPRM1	103:107	arg1	polymorphism					133:144	OPRM1 A118G single nucleotide polymorphism	103:144	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR)	99:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	33	theme	OPRM1	103:107	arg1	SNP					147:149	SNP rs1799971	147:159	SNP rs1799971	147:159	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	34	theme	µ-opioid	193:200	arg1	receptor					202:209	the N40D µ-opioid receptor	184:209	the N40D µ-opioid receptor (MOR)	184:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	34	theme	µ-opioid	193:200	arg1	MOR					212:214	MOR	212:214	MOR	212:214	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	0	35	theme	N40D	21:24	arg1	receptor					36:43	N40D mu-opioid receptor	21:43	N40D mu-opioid receptor variant	21:51	Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.
31481756	8	36	theme	neurophysiological	1346:1363	arg1	differences					1379:1389	neurophysiological and molecular differences	1346:1389	neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals	1346:1509	This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
31481756	1	37	theme	A118G	109:113	arg1	polymorphism					133:144	OPRM1 A118G single nucleotide polymorphism	103:144	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR)	99:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	37	theme	A118G	109:113	arg1	SNP					147:149	SNP rs1799971	147:159	SNP rs1799971	147:159	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	6	38	theme	variation	1044:1052	arg1	effects					1014:1020	the confounding effects	998:1020	the confounding effects of background genetic variation on neuronal function	998:1073	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	7	39	theme	biochemical	1235:1245	arg1	analysis					1247:1254	biochemical analysis	1235:1254	biochemical analysis	1235:1254	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	3	40	theme	abuse-related	434:446	arg1	deaths					448:453	opioid abuse-related deaths	427:453	opioid abuse-related deaths rising at unprecedented rates	427:483	With opioid abuse-related deaths rising at unprecedented rates, understanding these mechanisms may provide a path to therapy.
31481756	6	41	theme	engineered	1180:1189	arg1	iNs					1205:1207	independently engineered isogenic N40D iNs	1166:1207	independently engineered isogenic N40D iNs	1166:1207	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	6	42	from	effects	1091:1097	arg1	transmission					1119:1130	synaptic transmission	1110:1130	synaptic transmission	1110:1130	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	4	43	theme	inhibitory	607:616	arg1	cells					627:631	induced inhibitory neuronal cells	599:631	induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	599:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	43	theme	inhibitory	607:616	arg1	iNs					634:636	iNs	634:636	iNs	634:636	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	0	44	theme	receptor	36:43	arg1	variant					45:51	N40D mu-opioid receptor variant	21:51	N40D mu-opioid receptor variant	21:51	Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.
31481756	1	45	theme	abuse	283:287	arg1	dependence					242:251	dependence	242:251	dependence on opiates and other drugs of abuse	242:287	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	46	from	dependence	242:251	arg1	drugs					274:278	other drugs	268:278	other drugs	268:278	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	46	from	dependence	242:251	arg1	opiates					256:262	opiates	256:262	opiates	256:262	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	8	47	theme	altered	1435:1441	arg1	responsivity					1450:1461	altered opioid responsivity	1435:1461	altered opioid responsivity	1435:1461	This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
31481756	5	48	theme	D40	840:842	arg1	iNs					844:846	D40 iNs	840:846	D40 iNs	840:846	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	4	49	theme	induced	599:605	arg1	cells					627:631	induced inhibitory neuronal cells	599:631	induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	599:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	49	theme	induced	599:605	arg1	iNs					634:636	iNs	634:636	iNs	634:636	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	0	50	theme	synaptic	63:70	arg1	function					72:79	synaptic function	63:79	synaptic function in human neurons	63:96	Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.
31481756	0	51	from	function	72:79	arg1	neurons					90:96	human neurons	84:96	human neurons	84:96	Addiction associated N40D mu-opioid receptor variant modulates synaptic function in human neurons.
31481756	4	52	dep	subject-specific	582:597	arg1	cells					627:631	induced inhibitory neuronal cells	599:631	induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	599:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	52	dep	subject-specific	582:597	arg1	iNs					634:636	iNs	634:636	iNs	634:636	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	6	53	theme	neuronal	1057:1064	arg1	function					1066:1073	neuronal function	1057:1073	neuronal function	1057:1073	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	1	54	theme	single	115:120	arg1	polymorphism					133:144	OPRM1 A118G single nucleotide polymorphism	103:144	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR)	99:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	54	theme	single	115:120	arg1	SNP					147:149	SNP rs1799971	147:159	SNP rs1799971	147:159	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	2	55	theme	~3	396:397	arg1	%					398:398	~3%	396:398	~3% in African-Americans	396:419	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	7	56	theme	differential	1269:1280	arg1	glycosylation					1291:1303	differential N-linked glycosylation	1269:1303	differential N-linked glycosylation of human MOR N40D	1269:1321	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	5	57	theme	multiple	967:974	arg1	subjects					976:983	multiple subjects	967:983	multiple subjects	967:983	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	8	58	theme	MOR	1405:1407	arg1	variants					1409:1416	human MOR variants	1399:1416	human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals	1399:1509	This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
31481756	1	59	theme	nucleotide	122:131	arg1	polymorphism					133:144	OPRM1 A118G single nucleotide polymorphism	103:144	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR)	99:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	1	59	theme	nucleotide	122:131	arg1	SNP					147:149	SNP rs1799971	147:159	SNP rs1799971	147:159	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	8	60	theme	human	1399:1403	arg1	variants					1409:1416	human MOR variants	1399:1416	human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals	1399:1509	This study identifies neurophysiological and molecular differences between human MOR variants that may predict altered opioid responsivity and/or dependence in this subset of individuals.
31481756	7	61	theme	human	1308:1312	arg1	N40D					1318:1321	human MOR N40D	1308:1321	human MOR N40D	1308:1321	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	4	62	theme	stem	676:679	arg1	lines					692:696	seven human-induced pluripotent stem (iPS) cell lines	644:696	seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	644:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	7	63	theme	MOR	1314:1316	arg1	N40D					1318:1321	human MOR N40D	1308:1321	human MOR N40D	1308:1321	In addition, we employed biochemical analysis and observed differential N-linked glycosylation of human MOR N40D.
31481756	5	64	theme	spontaneous	906:916	arg1	sIPSCs					952:957	sIPSCs	952:957	sIPSCs	952:957	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	5	64	theme	spontaneous	906:916	arg1	currents					942:949	spontaneous inhibitory postsynaptic currents	906:949	spontaneous inhibitory postsynaptic currents (sIPSCs)	906:958	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	2	65	from	%	360:360	arg1	Europeans					381:389	Europeans	381:389	Europeans	381:389	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	65	from	%	360:360	arg1	Asians					365:370	Asians	365:370	Asians	365:370	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	65	from	%	360:360	arg1	African-Americans					403:419	African-Americans	403:419	African-Americans	403:419	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	1	66	theme	polymorphism	133:144	arg1	variant					167:173	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant	99:173	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR)	99:215	The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
31481756	6	67	theme	regulatory	1080:1089	arg1	effects					1091:1097	the regulatory effects	1076:1097	the regulatory effects of MORs on synaptic transmission	1076:1130	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	6	68	theme	MORs	1102:1105	arg1	effects					1091:1097	the regulatory effects	1076:1097	the regulatory effects of MORs on synaptic transmission	1076:1130	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	5	69	theme	inhibitory	918:927	arg1	sIPSCs					952:957	sIPSCs	952:957	sIPSCs	952:957	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	5	69	theme	inhibitory	918:927	arg1	currents					942:949	spontaneous inhibitory postsynaptic currents	906:949	spontaneous inhibitory postsynaptic currents (sIPSCs)	906:958	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	4	70	dep	subjects	703:710	arg1	male					738:741	male	738:741	male	738:741	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	4	70	dep	subjects	703:710	arg1	female					747:752	female	747:752	female	747:752	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	3	71	theme	unprecedented	465:477	arg1	rates					479:483	unprecedented rates	465:483	unprecedented rates	465:483	With opioid abuse-related deaths rising at unprecedented rates, understanding these mechanisms may provide a path to therapy.
31481756	4	72	theme	iPS	682:684	arg1	lines					692:696	seven human-induced pluripotent stem (iPS) cell lines	644:696	seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	644:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	6	73	theme	genetic	1036:1042	arg1	variation					1044:1052	background genetic variation	1025:1052	background genetic variation	1025:1052	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	5	74	theme	postsynaptic	929:940	arg1	sIPSCs					952:957	sIPSCs	952:957	sIPSCs	952:957	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	5	74	theme	postsynaptic	929:940	arg1	currents					942:949	spontaneous inhibitory postsynaptic currents	906:949	spontaneous inhibitory postsynaptic currents (sIPSCs)	906:958	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	4	75	theme	subject-specific	582:597	arg1	N40D					577:580	homozygous N40D	566:580	homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	566:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	2	76	theme	carriers	345:352	arg1	%					360:360	~40%	357:360	~40% in Asians	357:370	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	76	theme	carriers	345:352	arg1	frequency					323:331	The frequency	319:331	The frequency of G-allele carriers	319:352	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	6	77	theme	confounding	1002:1012	arg1	effects					1014:1020	the confounding effects	998:1020	the confounding effects of background genetic variation on neuronal function	998:1073	To mitigate the confounding effects of background genetic variation on neuronal function, the regulatory effects of MORs on synaptic transmission were recapitulated in two sets of independently engineered isogenic N40D iNs.
31481756	4	78	theme	homozygous	566:575	arg1	N40D					577:580	homozygous N40D	566:580	homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	566:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31481756	5	79	theme	currents	942:949	arg1	suppression					878:888	consistently stronger suppression	856:888	consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs)	856:958	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	5	79	theme	currents	942:949	arg1	N40					898:900	N40	898:900	N40	898:900	We found that D40 iNs exhibit consistently stronger suppression (versus N40) of spontaneous inhibitory postsynaptic currents (sIPSCs) across multiple subjects.
31481756	2	80	from	%	376:376	arg1	Europeans					381:389	Europeans	381:389	Europeans	381:389	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	80	from	%	376:376	arg1	Asians					365:370	Asians	365:370	Asians	365:370	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	80	from	%	376:376	arg1	African-Americans					403:419	African-Americans	403:419	African-Americans	403:419	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	2	81	theme	G-allele	336:343	arg1	carriers					345:352	G-allele carriers	336:352	G-allele carriers	336:352	The frequency of G-allele carriers is ~40% in Asians, ~16% in Europeans, and ~3% in African-Americans.
31481756	4	82	theme	pluripotent	664:674	arg1	lines					692:696	seven human-induced pluripotent stem (iPS) cell lines	644:696	seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female)	644:753	Here we generated homozygous N40D subject-specific induced inhibitory neuronal cells (iNs) from seven human-induced pluripotent stem (iPS) cell lines from subjects of European descent (both male and female) and probed the impact of N40D MOR regulation on synaptic transmission.
31336868	6	0	theme	corresponding	2124:2136	arg1	40a					2173:2175	40a	2173:2175	40a	2173:2175	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	6	0	theme	corresponding	2124:2136	arg1	drug					2167:2170	the corresponding D-gluco-piperidine miglustat drug	2120:2170	the corresponding D-gluco-piperidine miglustat drug (40a)	2120:2176	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	5	1	dep	substituent	1979:1989	arg1	40a					1992:1994	40a	1992:1994	40a	1992:1994	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	7	2	theme	β-glucosidase	2297:2309	arg1	inhibitors					2311:2320	the strongest β-glucosidase inhibitors	2283:2320	the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM	2283:2352	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	7	2	theme	β-glucosidase	2297:2309	arg1	L-ido-azepane					2250:2262	L-ido-azepane	2250:2262	L-ido-azepane (41b)	2250:2268	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	7	2	theme	β-glucosidase	2297:2309	arg1	miglitol					2231:2238	miglitol	2231:2238	miglitol (41a)	2231:2244	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	1	3	theme	disease	275:281	arg1	treatment					241:249	treatment	241:249	treatment of diabetes and Gaucher disease	241:281	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	3	theme	disease	275:281	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	3	theme	disease	275:281	arg1	activities					302:311	immunosuppressive activities	284:311	immunosuppressive activities	284:311	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	3	4	theme	ring	1199:1202	arg1	size					1204:1207	ring size	1199:1207	ring size	1199:1207	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	5	5	dep	configuration	1762:1774	arg1	C-5					1785:1787	C-5	1785:1787	C-5	1785:1787	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	5	5	dep	configuration	1762:1774	arg1	C-2					1777:1779	C-2	1777:1779	C-2	1777:1779	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	2	6	theme	simple	874:879	arg1	chains					889:894	simple N-alkyl chains	874:894	simple N-alkyl chains	874:894	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	7	link	N-linked	757:764	arg1	1,5-dideoxy-1,5-imino-D-gulitol					539:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	1	8	theme	Marburg	426:432	arg1	viruses					434:440	Marburg viruses	426:440	Marburg viruses	426:440	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	9	theme	immunosuppressive	284:300	arg1	activities					302:311	immunosuppressive activities	284:311	immunosuppressive activities	284:311	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	6	10	theme	µM	2113:2114	arg1	IC50					2105:2108	IC50	2105:2108	IC50 80 µM	2105:2114	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	5	11	theme	novel	1806:1810	arg1	27a					1831:1833	27a	1831:1833	27a	1831:1833	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	5	11	theme	novel	1806:1810	arg1	L-gulo-piperidine					1812:1828	novel L-gulo-piperidine	1806:1828	novel L-gulo-piperidine (27a)	1806:1834	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	2	12	theme	inverted	597:604	arg1	configuration					606:618	inverted configuration	597:618	inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)	597:681	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	13	theme	D-manno-azepane	722:736	arg1	cores					751:755	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores	515:755	cores	751:755	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	13	theme	D-manno-azepane	722:736	arg1	derivatives					738:748	D-manno-azepane derivatives	722:748	D-manno-azepane derivatives	722:748	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	3	14	theme	common	1266:1271	arg1	D-mannitol					1284:1293	D-mannitol	1284:1293	D-mannitol	1284:1293	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	3	14	theme	common	1266:1271	arg1	precursor					1273:1281	a common precursor	1264:1281	a common precursor	1264:1281	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	4	15	theme	inhibitors	1407:1416	arg1	evaluation					1377:1386	The evaluation	1373:1386	The evaluation of the prospective inhibitors on glucosidases	1373:1432	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	1	16	theme	therapeutic	207:217	arg1	treatment					241:249	treatment	241:249	treatment of diabetes and Gaucher disease	241:281	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	16	theme	therapeutic	207:217	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	16	theme	therapeutic	207:217	arg1	activities					302:311	immunosuppressive activities	284:311	immunosuppressive activities	284:311	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	16	theme	therapeutic	207:217	arg1	applications					219:230	broad therapeutic applications	201:230	broad therapeutic applications	201:230	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	2	17	theme	previous	498:505	arg1	work					507:510	our previous work	494:510	our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units	494:806	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	18	theme	different	769:777	arg1	units					802:806	glucopyranose units	788:806	glucopyranose units	788:806	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	18	theme	different	769:777	arg1	sites					779:783	different sites	769:783	different sites of glucopyranose units	769:806	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	5	19	theme	N-butyl	1971:1977	arg1	substituent					1979:1989	the same N-butyl substituent	1962:1989	the same N-butyl substituent (40a, IC50 172 µM)	1962:2008	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	2	20	theme	glucose-based	1023:1035	arg1	derivatives					1045:1055	the corresponding glucose-based N-alkyl derivatives	1005:1055	the corresponding glucose-based N-alkyl derivatives	1005:1055	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	21	theme	N-linked	757:764	arg1	1,5-dideoxy-1,5-imino-D-gulitol					539:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	5	22	theme	comparable	1933:1942	arg1	IC50					1898:1901	IC50 109 and 184 µM	1898:1916	IC50	1898:1901	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	2	23	theme	N-alkyl	881:887	arg1	chains					889:894	simple N-alkyl chains	874:894	simple N-alkyl chains	874:894	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	24	theme	isomeric	530:537	arg1	1,5-dideoxy-1,5-imino-D-gulitol					539:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	4	25	theme	IC50	1670:1673	arg1	µM					1679:1680	IC50 134 µM	1670:1680	IC50 134 µM	1670:1680	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	4	25	theme	IC50	1670:1673	arg1	reference					1659:1667	reference	1659:1667	reference (IC50 134 µM)	1659:1681	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	2	26	theme	DNJ	1060:1062	arg1	profile					994:1000	the inhibition profile	979:1000	the inhibition profile of the corresponding glucose-based N-alkyl derivatives	979:1055	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	26	theme	DNJ	1060:1062	arg1	cores					1064:1068	DNJ cores	1060:1068	DNJ cores found in miglustat and miglitol drugs	1060:1106	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	3	27	theme	SN2	1312:1314	arg1	reaction					1333:1340	an SN2 aminocyclization reaction	1309:1340	an SN2 aminocyclization reaction	1309:1340	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	5	28	theme	172	2002:2004	arg1	µM					2006:2007	µM	2006:2007	µM	2006:2007	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	1	29	theme	potent	137:142	arg1	analogues					123:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	29	theme	potent	137:142	arg1	inhibitors					144:153	potent inhibitors	137:153	potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus	137:482	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	2	30	theme	derivatives	1045:1055	arg1	profile					994:1000	the inhibition profile	979:1000	the inhibition profile of the corresponding glucose-based N-alkyl derivatives	979:1055	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	30	theme	derivatives	1045:1055	arg1	cores					1064:1068	DNJ cores	1060:1068	DNJ cores found in miglustat and miglitol drugs	1060:1106	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	31	theme	1,6-dideoxy-1,6-imino-D-mannitol	688:719	arg1	cores					751:755	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores	515:755	cores	751:755	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	31	theme	1,6-dideoxy-1,6-imino-D-mannitol	688:719	arg1	derivatives					738:748	D-manno-azepane derivatives	722:748	D-manno-azepane derivatives	722:748	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	0	32	from	Effects	13:19	arg1	Activities					86:95	Glucosidase Activities	74:95	Glucosidase Activities	74:95	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.
31336868	0	33	theme	N-Substituents	56:69	arg1	Effects					13:19	Effects	13:19	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.	0:96	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.
31336868	2	34	theme	accessed	945:952	arg1	scaffolds					954:962	these easily accessed scaffolds	932:962	these easily accessed scaffolds	932:962	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	35	located	found	1070:1074	arg1	miglustat					1079:1087	miglustat	1079:1087	miglustat	1079:1087	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	35	located	found	1070:1074	arg2	cores					1064:1068	DNJ cores	1060:1068	DNJ cores found in miglustat and miglitol drugs	1060:1106	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	35	located	found	1070:1074	arg2	profile					994:1000	the inhibition profile	979:1000	the inhibition profile of the corresponding glucose-based N-alkyl derivatives	979:1055	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	35	located	found	1070:1074	arg1	drugs					1102:1106	miglitol drugs	1093:1106	miglitol drugs	1093:1106	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	0	36	theme	Glucosidase	74:84	arg1	Activities					86:95	Glucosidase Activities	74:95	Glucosidase Activities	74:95	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.
31336868	1	37	theme	hepatitis	372:380	arg1	C					382:382	hepatitis C	372:382	hepatitis C	372:382	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	37	theme	hepatitis	372:380	arg1	HIV					362:364	HIV	362:364	HIV	362:364	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	6	38	theme	ring	2045:2048	arg1	L-ido-azepane					2050:2062	the seven-membered ring L-ido-azepane	2026:2062	the seven-membered ring L-ido-azepane (40b)	2026:2068	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	6	38	theme	ring	2045:2048	arg1	40b					2065:2067	40b	2065:2067	40b	2065:2067	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	2	39	from	C-5	631:633	arg1	configuration					606:618	inverted configuration	597:618	inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)	597:681	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	39	from	C-5	631:633	arg1	respect					638:644	respect	638:644	respect to glucose or deoxynojirimycin (DNJ)	638:681	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	40	from	studies	825:831	arg1	iminosugars					854:864	these alternative iminosugars	836:864	these alternative iminosugars bearing simple N-alkyl chains	836:894	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	4	41	dep	D-gluco-piperidine	1455:1472	arg1	miglitol					1475:1482	miglitol	1475:1482	miglitol	1475:1482	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	4	41	dep	D-gluco-piperidine	1455:1472	arg1	41b					1509:1511	41b	1509:1511	41b	1509:1511	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	4	41	dep	D-gluco-piperidine	1455:1472	arg1	41a					1485:1487	41a	1485:1487	41a	1485:1487	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	1	42	theme	N-substituted	98:110	arg1	analogues					123:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	42	theme	N-substituted	98:110	arg1	inhibitors					144:153	potent inhibitors	137:153	potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus	137:482	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	0	43	theme	Stereochemistry	24:38	arg1	Effects					13:19	Effects	13:19	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.	0:96	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.
31336868	7	44	theme	µM	2351:2352	arg1	IC50					2341:2344	IC50	2341:2344	IC50 of 4 µM	2341:2352	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	0	45	theme	Ring	41:44	arg1	Size					46:49	Ring Size	41:49	Ring Size	41:49	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.
31336868	5	46	theme	configuration	1762:1774	arg1	derivatives					1790:1800	glucose-inverted configuration (C-2 and C-5) derivatives	1745:1800	glucose-inverted configuration (C-2 and C-5) derivatives	1745:1800	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	3	47	theme	iminosugars	1134:1144	arg1	library					1123:1129	a small library	1115:1129	a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions	1115:1228	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	4	48	dep	IC50	1609:1612	arg1	µM					1628:1629	µM and 138 µM	1617:1629	IC50 41 µM and 138 µM	1609:1629	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	2	49	theme	glucopyranose	788:800	arg1	units					802:806	glucopyranose units	788:806	glucopyranose units	788:806	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	50	theme	alternative	842:852	arg1	iminosugars					854:864	these alternative iminosugars	836:864	these alternative iminosugars bearing simple N-alkyl chains	836:894	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	1	51	theme	dengue	471:476	arg1	virus					478:482	dengue virus	471:482	dengue virus	471:482	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	5	52	theme	β-glucosidase	1703:1715	arg1	inhibition					1717:1726	β-glucosidase inhibition	1703:1726	β-glucosidase inhibition	1703:1726	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	1	53	theme	diabetes	254:261	arg1	treatment					241:249	treatment	241:249	treatment of diabetes and Gaucher disease	241:281	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	53	theme	diabetes	254:261	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	53	theme	diabetes	254:261	arg1	activities					302:311	immunosuppressive activities	284:311	immunosuppressive activities	284:311	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	3	54	theme	different	1172:1180	arg1	stereochemistry					1182:1196	different stereochemistry	1172:1196	different stereochemistry	1172:1196	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	0	55	dep	Iminosugars	0:10	arg1	Effects					13:19	Effects	13:19	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.	0:96	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.
31336868	7	56	with	series	2329:2334	arg1	IC50					2341:2344	IC50	2341:2344	IC50 of 4 µM	2341:2352	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	1	57	theme	Gaucher	267:273	arg1	disease					275:281	Gaucher disease	267:281	Gaucher disease	267:281	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	2	58	from	work	507:510	arg1	1,5-dideoxy-1,5-imino-D-gulitol					539:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	58	from	work	507:510	arg1	cores					751:755	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores	515:755	cores	751:755	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	58	from	work	507:510	arg1	derivatives					738:748	D-manno-azepane derivatives	722:748	D-manno-azepane derivatives	722:748	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	7	59	theme	strongest	2287:2295	arg1	inhibitors					2311:2320	the strongest β-glucosidase inhibitors	2283:2320	the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM	2283:2352	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	7	59	theme	strongest	2287:2295	arg1	L-ido-azepane					2250:2262	L-ido-azepane	2250:2262	L-ido-azepane (41b)	2250:2268	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	7	59	theme	strongest	2287:2295	arg1	miglitol					2231:2238	miglitol	2231:2238	miglitol (41a)	2231:2244	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	1	60	theme	glycosyltransferases	175:194	arg1	analogues					123:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	60	theme	glycosyltransferases	175:194	arg1	inhibitors					144:153	potent inhibitors	137:153	potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus	137:482	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	6	61	theme	80	2110:2111	arg1	µM					2113:2114	µM	2113:2114	µM	2113:2114	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	1	62	theme	broad	201:205	arg1	treatment					241:249	treatment	241:249	treatment of diabetes and Gaucher disease	241:281	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	62	theme	broad	201:205	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	62	theme	broad	201:205	arg1	activities					302:311	immunosuppressive activities	284:311	immunosuppressive activities	284:311	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	62	theme	broad	201:205	arg1	applications					219:230	broad therapeutic applications	201:230	broad therapeutic applications	201:230	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	5	63	theme	same	1966:1969	arg1	substituent					1979:1989	the same N-butyl substituent	1962:1989	the same N-butyl substituent (40a, IC50 172 µM)	1962:2008	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	2	64	theme	N-alkyl	1037:1043	arg1	derivatives					1045:1055	the corresponding glucose-based N-alkyl derivatives	1005:1055	the corresponding glucose-based N-alkyl derivatives	1005:1055	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	65	dep	1,5-dideoxy-1,5-imino-D-gulitol	539:569	arg1	L-gulo-piperidines					572:589	L-gulo-piperidines	572:589	L-gulo-piperidines	572:589	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	66	theme	corresponding	1009:1021	arg1	derivatives					1045:1055	the corresponding glucose-based N-alkyl derivatives	1005:1055	the corresponding glucose-based N-alkyl derivatives	1005:1055	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	4	67	from	evaluation	1377:1386	arg1	glucosidases					1421:1432	glucosidases	1421:1432	glucosidases	1421:1432	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	4	68	theme	prospective	1395:1405	arg1	inhibitors					1407:1416	the prospective inhibitors	1391:1416	the prospective inhibitors	1391:1416	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	4	69	theme	134	1675:1677	arg1	µM					1679:1680	IC50 134 µM	1670:1680	IC50 134 µM	1670:1680	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	4	69	theme	134	1675:1677	arg1	reference					1659:1667	reference	1659:1667	reference (IC50 134 µM)	1659:1681	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	1	70	theme	iminosugar	112:121	arg1	analogues					123:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	70	theme	iminosugar	112:121	arg1	inhibitors					144:153	potent inhibitors	137:153	potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus	137:482	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	6	71	theme	drug	2167:2170	arg1	activity					2095:2102	the activity	2091:2102	the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a)	2091:2176	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	2	72	theme	functionalized	515:528	arg1	1,5-dideoxy-1,5-imino-D-gulitol					539:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol	515:569	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	73	from	C-2	623:625	arg1	configuration					606:618	inverted configuration	597:618	inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)	597:681	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	73	from	C-2	623:625	arg1	respect					638:644	respect	638:644	respect to glucose or deoxynojirimycin (DNJ)	638:681	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	3	74	theme	aminocyclization	1316:1331	arg1	reaction					1333:1340	an SN2 aminocyclization reaction	1309:1340	an SN2 aminocyclization reaction	1309:1340	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	5	75	theme	µM	2006:2007	arg1	IC50					1997:2000	IC50	1997:2000	IC50 172 µM	1997:2007	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	4	76	theme	D-gluco-piperidine	1455:1472	arg1	DNJ-derivatives					1514:1528	merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives	1448:1528	merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group	1448:1562	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	1	77	with	glucosidases	158:169	arg1	treatment					241:249	treatment	241:249	treatment of diabetes and Gaucher disease	241:281	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	77	with	glucosidases	158:169	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	77	with	glucosidases	158:169	arg1	activities					302:311	immunosuppressive activities	284:311	immunosuppressive activities	284:311	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	77	with	glucosidases	158:169	arg1	applications					219:230	broad therapeutic applications	201:230	broad therapeutic applications	201:230	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	78	theme	glucosidases	158:169	arg1	analogues					123:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues	98:131	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	78	theme	glucosidases	158:169	arg1	inhibitors					144:153	potent inhibitors	137:153	potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus	137:482	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	5	79	with	miglustat	1947:1955	arg1	substituent					1979:1989	the same N-butyl substituent	1962:1989	the same N-butyl substituent (40a, IC50 172 µM)	1962:2008	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	3	80	theme	isomeric	1350:1357	arg1	bis-epoxides					1359:1370	two isomeric bis-epoxides	1346:1370	two isomeric bis-epoxides	1346:1370	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	6	81	theme	seven-membered	2030:2043	arg1	L-ido-azepane					2050:2062	the seven-membered ring L-ido-azepane	2026:2062	the seven-membered ring L-ido-azepane (40b)	2026:2068	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	6	81	theme	seven-membered	2030:2043	arg1	40b					2065:2067	40b	2065:2067	40b	2065:2067	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	2	82	theme	inhibition	983:992	arg1	profile					994:1000	the inhibition profile	979:1000	the inhibition profile of the corresponding glucose-based N-alkyl derivatives	979:1055	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	82	theme	inhibition	983:992	arg1	cores					1064:1068	DNJ cores	1060:1068	DNJ cores found in miglustat and miglitol drugs	1060:1106	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	5	83	theme	other	1691:1695	arg1	hand					1697:1700	the other hand	1687:1700	the other hand	1687:1700	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	1	84	theme	bovine	385:390	arg1	BVDV					402:405	BVDV	402:405	BVDV	402:405	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	84	theme	bovine	385:390	arg1	diarrhea					392:399	bovine diarrhea	385:399	bovine diarrhea (BVDV)	385:406	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	84	theme	bovine	385:390	arg1	HIV					362:364	HIV	362:364	HIV	362:364	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	3	85	theme	small	1117:1121	arg1	library					1123:1129	a small library	1115:1129	a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions	1115:1228	Thus, a small library of iminosugars (14 compounds) displaying different stereochemistry, ring size, and N-substitutions was successfully synthesized from a common precursor, D-mannitol, by utilizing an SN2 aminocyclization reaction via two isomeric bis-epoxides.
31336868	5	86	theme	N-butyl	1878:1884	arg1	chain					1886:1890	the N-butyl chain	1874:1890	the N-butyl chain	1874:1890	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	4	87	theme	N-hydroxylethyl	1542:1556	arg1	group					1558:1562	the N-hydroxylethyl group	1538:1562	the N-hydroxylethyl group	1538:1562	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	6	88	dep	activity	2095:2102	arg1	IC50					2105:2108	IC50	2105:2108	IC50 80 µM	2105:2114	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	1	89	theme	antibacterial	318:330	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	4	90	theme	L-ido-azepane	1494:1506	arg1	DNJ-derivatives					1514:1528	merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives	1448:1528	merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group	1448:1562	The evaluation of the prospective inhibitors on glucosidases revealed that merely D-gluco-piperidine (miglitol, 41a) and L-ido-azepane (41b) DNJ-derivatives bearing the N-hydroxylethyl group showed inhibition towards α-glucosidase with IC50 41 µM and 138 µM, respectively, using DNJ as reference (IC50 134 µM).
31336868	0	91	theme	Size	46:49	arg1	Effects					13:19	Effects	13:19	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.	0:96	Iminosugars: Effects of Stereochemistry, Ring Size, and N-Substituents on Glucosidase Activities.
31336868	1	92	theme	antiviral	336:344	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	6	93	theme	D-gluco-piperidine	2138:2155	arg1	40a					2173:2175	40a	2173:2175	40a	2173:2175	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	6	93	theme	D-gluco-piperidine	2138:2155	arg1	drug					2167:2170	the corresponding D-gluco-piperidine miglustat drug	2120:2170	the corresponding D-gluco-piperidine miglustat drug (40a)	2120:2176	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	7	94	theme	α-glucosidase	2200:2212	arg1	inhibition					2214:2223	α-glucosidase inhibition	2200:2223	α-glucosidase inhibition	2200:2223	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	5	95	theme	glucose-inverted	1745:1760	arg1	configuration					1762:1774	glucose-inverted configuration	1745:1774	glucose-inverted configuration (C-2 and C-5) derivatives	1745:1800	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	1	96	with	glycosyltransferases	175:194	arg1	treatment					241:249	treatment	241:249	treatment of diabetes and Gaucher disease	241:281	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	96	with	glycosyltransferases	175:194	arg1	effects					346:352	antibacterial and antiviral effects	318:352	antibacterial and antiviral effects	318:352	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	96	with	glycosyltransferases	175:194	arg1	activities					302:311	immunosuppressive activities	284:311	immunosuppressive activities	284:311	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	1	96	with	glycosyltransferases	175:194	arg1	applications					219:230	broad therapeutic applications	201:230	broad therapeutic applications	201:230	N-substituted iminosugar analogues are potent inhibitors of glucosidases and glycosyltransferases with broad therapeutic applications, such as treatment of diabetes and Gaucher disease, immunosuppressive activities, and antibacterial and antiviral effects against HIV, HPV, hepatitis C, bovine diarrhea (BVDV), Ebola (EBOV) and Marburg viruses (MARV), influenza, Zika, and dengue virus.
31336868	2	97	theme	units	802:806	arg1	units					802:806	glucopyranose units	788:806	glucopyranose units	788:806	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	2	97	theme	units	802:806	arg1	sites					779:783	different sites	769:783	different sites of glucopyranose units	769:806	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
31336868	7	98	theme	series	2329:2334	arg1	inhibitors					2311:2320	the strongest β-glucosidase inhibitors	2283:2320	the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM	2283:2352	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	7	98	theme	series	2329:2334	arg1	L-ido-azepane					2250:2262	L-ido-azepane	2250:2262	L-ido-azepane (41b)	2250:2268	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	7	98	theme	series	2329:2334	arg1	miglitol					2231:2238	miglitol	2231:2238	miglitol (41a)	2231:2244	Furthermore, besides α-glucosidase inhibition, both miglitol (41a) and L-ido-azepane (41b) proved to be the strongest β-glucosidase inhibitors of the series with IC50 of 4 µM.
31336868	6	99	theme	miglustat	2157:2165	arg1	40a					2173:2175	40a	2173:2175	40a	2173:2175	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	6	99	theme	miglustat	2157:2165	arg1	drug					2167:2170	the corresponding D-gluco-piperidine miglustat drug	2120:2170	the corresponding D-gluco-piperidine miglustat drug (40a)	2120:2176	Interestingly, the seven-membered ring L-ido-azepane (40b) displayed near twice the activity (IC50 80 µM) of the corresponding D-gluco-piperidine miglustat drug (40a).
31336868	5	100	dep	40a	1992:1994	arg1	IC50					1997:2000	IC50	1997:2000	IC50 172 µM	1997:2007	On the other hand, β-glucosidase inhibition was achieved for glucose-inverted configuration (C-2 and C-5) derivatives, as novel L-gulo-piperidine (27a) and D-manno-azepane (27b), preserving the N-butyl chain, with IC50 109 and 184 µM, respectively, comparable to miglustat with the same N-butyl substituent (40a, IC50 172 µM).
31336868	2	101	theme	miglitol	1093:1100	arg1	drugs					1102:1106	miglitol drugs	1093:1106	miglitol drugs	1093:1106	Based on our previous work on functionalized isomeric 1,5-dideoxy-1,5-imino-D-gulitol (L-gulo-piperidines, with inverted configuration at C-2 and C-5 in respect to glucose or deoxynojirimycin (DNJ)) and 1,6-dideoxy-1,6-imino-D-mannitol (D-manno-azepane derivatives) cores N-linked to different sites of glucopyranose units, we continue our studies on these alternative iminosugars bearing simple N-alkyl chains instead of glucose to understand if these easily accessed scaffolds could preserve the inhibition profile of the corresponding glucose-based N-alkyl derivatives as DNJ cores found in miglustat and miglitol drugs.
30221662	4	0	located	observed	886:893	arg1	rats					898:901	rats	898:901	rats	898:901	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	0	located	observed	886:893	arg2	increases					689:697	Significant increases	677:697	Significant increases in the O‑GlcNAc modification	677:726	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	0	located	observed	886:893	arg2	accumulation					732:743	accumulation	732:743	accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited,	732:879	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	1	from	accumulation	732:743	arg1	modification					715:726	the O‑GlcNAc modification	702:726	the O‑GlcNAc modification	702:726	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	5	2	theme	exacerbated	1269:1279	arg1	abnormalities					1292:1304	exacerbated myocardial abnormalities	1269:1304	exacerbated myocardial abnormalities	1269:1304	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	1	3	theme	molecular	303:311	arg1	mechanisms					313:322	the molecular mechanisms	299:322	the molecular mechanisms between the two processes	299:348	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated.
30221662	10	4	theme	protein	2300:2306	arg1	SNAP29					2308:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	4	theme	protein	2300:2306	arg1	complex					2407:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex	2331:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2331:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	6	5	theme	O‑GlcNAc	1584:1591	arg1	modification					1593:1604	O‑GlcNAc modification	1584:1604	O‑GlcNAc modification	1584:1604	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	9	6	theme	inhibitor	2051:2059	arg1	3‑methyladenine					2061:2075	the autophagy inhibitor 3‑methyladenine	2037:2075	the autophagy inhibitor 3‑methyladenine	2037:2075	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	6	7	theme	diastolic	1661:1669	arg1	function					1671:1678	cardiac diastolic function	1653:1678	cardiac diastolic function	1653:1678	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	3	8	dep	STZ	661:663	arg1	55 mg/kg					666:673	55 mg/kg	666:673	STZ; 55 mg/kg	661:673	A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg).
30221662	8	9	theme	rats	1822:1825	arg1	myocardium					1799:1808	the myocardium	1795:1808	the myocardium of diabetic rats	1795:1825	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	9	10	theme	high	2095:2098	arg1	glucose					2100:2106	high glucose	2095:2106	high glucose	2095:2106	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	3	11	theme	streptozotocin	645:658	arg1	injection					632:640	intraperitoneal injection	616:640	intraperitoneal injection of streptozotocin (STZ; 55 mg/kg)	616:674	A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg).
30221662	8	12	theme	O‑GlcNAc	1864:1871	arg1	modification					1873:1884	O‑GlcNAc modification	1864:1884	O‑GlcNAc modification of SNAP29	1864:1894	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	7	13	theme	rat	1751:1753	arg1	NRCMs					1771:1775	NRCMs	1771:1775	NRCMs	1771:1775	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	7	13	theme	rat	1751:1753	arg1	cardiomyocytes					1755:1768	primary neonatal rat cardiomyocytes	1734:1768	primary neonatal rat cardiomyocytes (NRCMs)	1734:1776	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	4	14	theme	markers	762:768	arg1	increases					689:697	Significant increases	677:697	Significant increases in the O‑GlcNAc modification	677:726	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	14	theme	markers	762:768	arg1	accumulation					732:743	accumulation	732:743	accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited,	732:879	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	5	15	theme	deteriorated	1085:1096	arg1	function					1116:1123	deteriorated cardiac diastolic function	1085:1123	deteriorated cardiac diastolic function	1085:1123	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	5	16	theme	O‑GlcNAcase	964:974	arg1	inhibitor					976:984	the selective O‑GlcNAcase inhibitor	950:984	the selective O‑GlcNAcase inhibitor	950:984	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	5	16	theme	O‑GlcNAcase	964:974	arg1	G					995:995	thiamet G	987:995	thiamet G	987:995	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	7	17	theme	primary	1734:1740	arg1	NRCMs					1771:1775	NRCMs	1771:1775	NRCMs	1771:1775	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	7	17	theme	primary	1734:1740	arg1	cardiomyocytes					1755:1768	primary neonatal rat cardiomyocytes	1734:1768	primary neonatal rat cardiomyocytes (NRCMs)	1734:1776	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	4	18	theme	protein	793:799	arg1	chain					809:813	microtubule‑associated protein 1 light chain	770:813	microtubule‑associated protein 1 light chain 3α II/I	770:821	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	18	theme	protein	793:799	arg1	markers					762:768	the autophagy markers	748:768	the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited,	748:879	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	5	19	theme	interstitial	1369:1380	arg1	accumulation					1391:1402	interstitial fibrosis accumulation	1369:1402	interstitial fibrosis accumulation	1369:1402	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	11	20	dep	type	2739:2742	arg1	rats					2755:2758	diabetic rats	2746:2758	type I diabetic rats	2739:2758	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	5	21	theme	diastolic	1106:1114	arg1	function					1116:1123	deteriorated cardiac diastolic function	1085:1123	deteriorated cardiac diastolic function	1085:1123	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	2	22	theme	myocardial	546:555	arg1	injury					557:562	diabetic myocardial injury	537:562	diabetic myocardial injury	537:562	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	10	23	theme	membrane	2380:2387	arg1	SNAP29					2308:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	23	theme	membrane	2380:2387	arg1	complex					2407:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex	2331:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2331:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	0	24	theme	SNAP29-STX17-VAMP8	83:100	arg1	complex					102:108	the disturbed SNAP29-STX17-VAMP8 complex	69:108	the disturbed SNAP29-STX17-VAMP8 complex	69:108	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	8	25	theme	autophagic	1917:1926	arg1	flux					1928:1931	autophagic flux	1917:1931	autophagic flux	1917:1931	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	1	26	theme	O‑linked	173:180	arg1	modification					215:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated.
30221662	6	27	theme	isomerizing	1512:1522	arg1	6‑diazo‑5‑oxo‑L‑norleucine					1418:1443	6‑diazo‑5‑oxo‑L‑norleucine	1418:1443	6‑diazo‑5‑oxo‑L‑norleucine	1418:1443	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	6	27	theme	isomerizing	1512:1522	arg1	inhibitor					1449:1457	an inhibitor	1446:1457	an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1	1446:1524	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	5	28	theme	velocity/atrial	1185:1199	arg1	ratio					1232:1236	peak velocity/atrial contraction flow peak velocity ratio	1180:1236	peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1180:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	7	29	used	used	1716:1719	arg2	In vitro					1681:1688	In vitro	1681:1688	In vitro	1681:1688	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	7	29	used	used	1716:1719	arg2	glucose					1696:1702	high glucose	1691:1702	high glucose (25 mM)	1691:1710	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	10	30	theme	VAMP8	2400:2404	arg1	SNAP29					2308:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	30	theme	VAMP8	2400:2404	arg1	complex					2407:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex	2331:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2331:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	0	31	theme	myocardial	126:135	arg1	injury					137:142	myocardial injury	126:142	myocardial injury in type I diabetic rats	126:166	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	2	32	from	protein	514:520	arg1	injury					557:562	diabetic myocardial injury	537:562	diabetic myocardial injury	537:562	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	9	33	theme	autophagy	2191:2199	arg1	stage					2182:2186	the initial stage	2170:2186	the initial stage of autophagy	2170:2199	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	5	34	theme	left	1155:1158	arg1	ventricular					1160:1170	an increased left ventricular	1142:1170	an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1142:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	5	35	theme	O‑GlcNAc	1021:1028	arg1	modification					1030:1041	O‑GlcNAc modification	1021:1041	O‑GlcNAc modification	1021:1041	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	2	36	theme	synaptosomal‑associated	490:512	arg1	protein					514:520	O‑GlcNAc‑modified synaptosomal‑associated protein 29	472:523	O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury	472:562	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	2	36	theme	synaptosomal‑associated	490:512	arg1	SNAP29					526:531	SNAP29	526:531	SNAP29	526:531	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	10	37	theme	disease	2422:2428	arg1	progression					2430:2440	disease progression	2422:2440	disease progression	2422:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	4	38	theme	light	803:807	arg1	chain					809:813	microtubule‑associated protein 1 light chain	770:813	microtubule‑associated protein 1 light chain 3α II/I	770:821	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	38	theme	light	803:807	arg1	markers					762:768	the autophagy markers	748:768	the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited,	748:879	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	0	39	theme	O-GlcNAc-modified	0:16	arg1	SNAP29					18:23	O-GlcNAc-modified SNAP29	0:23	O-GlcNAc-modified SNAP29	0:23	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	11	40	theme	present	2447:2453	arg1	study					2455:2459	The present study	2443:2459	The present study	2443:2459	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	11	40	theme	present	2447:2453	arg1	first					2468:2472	first	2468:2472	first	2468:2472	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	11	41	theme	O‑GlcNAc	2538:2545	arg1	SNAP29					2525:2530	SNAP29	2525:2530	SNAP29	2525:2530	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	11	41	theme	O‑GlcNAc	2538:2545	arg1	substrate					2547:2555	an O‑GlcNAc substrate	2535:2555	an O‑GlcNAc substrate	2535:2555	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	11	42	theme	SNAP29‑STX17‑VAMP8	2615:2632	arg1	formation					2642:2650	SNAP29‑STX17‑VAMP8 complex formation	2615:2650	SNAP29‑STX17‑VAMP8 complex formation	2615:2650	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	8	43	with	Consistent	1779:1788	arg1	myocardium					1799:1808	the myocardium	1795:1808	the myocardium of diabetic rats	1795:1825	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	11	44	from	increase	2569:2576	arg1	SNAP29					2599:2604	O‑GlcNAc‑modified SNAP29	2581:2604	O‑GlcNAc‑modified SNAP29	2581:2604	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	2	45	theme	molecular	435:443	arg1	regulation					445:454	the molecular regulation	431:454	the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury	431:562	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	6	46	theme	O‑GlcNAc	1539:1546	arg1	antagonist					1548:1557	an O‑GlcNAc antagonist	1536:1557	an O‑GlcNAc antagonist	1536:1557	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	6	46	theme	O‑GlcNAc	1539:1546	arg1	6‑diazo‑5‑oxo‑L‑norleucine					1418:1443	6‑diazo‑5‑oxo‑L‑norleucine	1418:1443	6‑diazo‑5‑oxo‑L‑norleucine	1418:1443	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	6	46	theme	O‑GlcNAc	1539:1546	arg1	level					1575:1579	the level	1571:1579	the level	1571:1579	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	5	47	theme	flow	1213:1216	arg1	ratio					1232:1236	peak velocity/atrial contraction flow peak velocity ratio	1180:1236	peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1180:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	5	48	theme	autophagic	1068:1077	arg1	flux					1079:1082	autophagic flux	1068:1082	autophagic flux	1068:1082	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	9	49	theme	short	1957:1961	arg1	interference					1975:1986	the short hairpin RNA interference	1953:1986	the short hairpin RNA interference	1953:1986	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	4	50	dep	8 weeks	903:909	arg1	following					911:919	following	911:919	following	911:919	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	50	dep	8 weeks	903:909	arg1	induction					925:933	STZ induction	921:933	STZ induction	921:933	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	5	51	theme	velocity	1223:1230	arg1	ratio					1232:1236	peak velocity/atrial contraction flow peak velocity ratio	1180:1236	peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1180:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	9	52	theme	RNA	1971:1973	arg1	interference					1975:1986	the short hairpin RNA interference	1953:1986	the short hairpin RNA interference	1953:1986	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	11	53	theme	myocardial	2718:2727	arg1	injury					2729:2734	myocardial injury	2718:2734	myocardial injury in type I diabetic rats	2718:2758	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	6	54	theme	autophagic	1624:1633	arg1	flux					1635:1638	autophagic flux	1624:1638	autophagic flux	1624:1638	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	1	55	theme	diabetic	262:269	arg1	injury					282:287	diabetic myocardial injury	262:287	diabetic myocardial injury	262:287	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated.
30221662	10	56	theme	substrate	2290:2298	arg1	SNAP29					2308:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	56	theme	substrate	2290:2298	arg1	complex					2407:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex	2331:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2331:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	4	57	theme	autophagic	851:860	arg1	flux					862:865	autophagic flux	851:865	autophagic flux	851:865	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	10	58	used	used	2238:2241	arg2	co‑immunoprecipitation					2211:2232	co‑immunoprecipitation	2211:2232	co‑immunoprecipitation	2211:2232	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	2	59	theme	present	400:406	arg1	study					408:412	the present study	396:412	the present study	396:412	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	6	60	theme	modification	1593:1604	arg1	antagonist					1548:1557	an O‑GlcNAc antagonist	1536:1557	an O‑GlcNAc antagonist	1536:1557	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	6	60	theme	modification	1593:1604	arg1	6‑diazo‑5‑oxo‑L‑norleucine					1418:1443	6‑diazo‑5‑oxo‑L‑norleucine	1418:1443	6‑diazo‑5‑oxo‑L‑norleucine	1418:1443	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	6	60	theme	modification	1593:1604	arg1	level					1575:1579	the level	1571:1579	the level	1571:1579	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	5	61	dep	function	1116:1123	arg1	indicated					1129:1137	indicated	1129:1137	indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1129:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	3	62	theme	type	580:583	arg1	diabetes					587:594	type I diabetes	580:594	type I diabetes	580:594	A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg).
30221662	8	63	theme	diabetic	1813:1820	arg1	rats					1822:1825	diabetic rats	1813:1825	diabetic rats	1813:1825	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	5	64	theme	myocardial	1281:1290	arg1	abnormalities					1292:1304	exacerbated myocardial abnormalities	1269:1304	exacerbated myocardial abnormalities	1269:1304	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	4	65	theme	STZ	921:923	arg1	induction					925:933	STZ induction	921:933	STZ induction	921:933	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	10	66	theme	SNAP29	2308:2313	arg1	role					2260:2263	the role	2256:2263	the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2256:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	67	theme	O‑GlcNAc‑modified	2272:2288	arg1	SNAP29					2308:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	67	theme	O‑GlcNAc‑modified	2272:2288	arg1	complex					2407:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex	2331:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2331:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	1	68	theme	O‑GlcNAc	205:212	arg1	modification					215:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated.
30221662	8	69	mod	modification	1873:1884	arg3	O‑GlcNAc					1864:1871	O‑GlcNAc modification	1864:1884	O‑GlcNAc modification of SNAP29	1864:1894	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	8	69	mod	modification	1873:1884	arg1	SNAP29					1889:1894	SNAP29	1889:1894	SNAP29	1889:1894	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	9	70	theme	autophagy	2041:2049	arg1	3‑methyladenine					2061:2075	the autophagy inhibitor 3‑methyladenine	2037:2075	the autophagy inhibitor 3‑methyladenine	2037:2075	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	11	71	theme	O‑GlcNAc‑modified	2581:2597	arg1	SNAP29					2599:2604	O‑GlcNAc‑modified SNAP29	2581:2604	O‑GlcNAc‑modified SNAP29	2581:2604	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	4	72	theme	O‑GlcNAc	706:713	arg1	modification					715:726	the O‑GlcNAc modification	702:726	the O‑GlcNAc modification	702:726	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	0	73	theme	diabetic	154:161	arg1	rats					163:166	diabetic rats	154:166	type I diabetic rats	147:166	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	3	74	theme	diabetes	587:594	arg1	model					571:575	A rat model	565:575	A rat model of type I diabetes	565:594	A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg).
30221662	6	75	theme	cardiac	1653:1659	arg1	function					1671:1678	cardiac diastolic function	1653:1678	cardiac diastolic function	1653:1678	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	4	76	from	increases	689:697	arg1	modification					715:726	the O‑GlcNAc modification	702:726	the O‑GlcNAc modification	702:726	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	7	77	theme	neonatal	1742:1749	arg1	NRCMs					1771:1775	NRCMs	1771:1775	NRCMs	1771:1775	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	7	77	theme	neonatal	1742:1749	arg1	cardiomyocytes					1755:1768	primary neonatal rat cardiomyocytes	1734:1768	primary neonatal rat cardiomyocytes (NRCMs)	1734:1776	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	11	78	theme	autophagy	2691:2699	arg1	degradation					2676:2686	the degradation	2672:2686	the degradation of autophagy	2672:2699	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	4	79	theme	Significant	677:687	arg1	increases					689:697	Significant increases	677:697	Significant increases in the O‑GlcNAc modification	677:726	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	3	80	theme	intraperitoneal	616:630	arg1	injection					632:640	intraperitoneal injection	616:640	intraperitoneal injection of streptozotocin (STZ; 55 mg/kg)	616:674	A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg).
30221662	5	81	theme	selective	954:962	arg1	inhibitor					976:984	the selective O‑GlcNAcase inhibitor	950:984	the selective O‑GlcNAcase inhibitor	950:984	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	5	81	theme	selective	954:962	arg1	G					995:995	thiamet G	987:995	thiamet G	987:995	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	9	82	theme	autophagy‑mediated	2118:2135	arg1	degradation					2137:2147	autophagy‑mediated degradation	2118:2147	autophagy‑mediated degradation	2118:2147	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	4	83	theme	autophagy	752:760	arg1	chain					809:813	microtubule‑associated protein 1 light chain	770:813	microtubule‑associated protein 1 light chain 3α II/I	770:821	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	83	theme	autophagy	752:760	arg1	markers					762:768	the autophagy markers	748:768	the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited,	748:879	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	83	theme	autophagy	752:760	arg1	P62					827:829	P62	827:829	P62	827:829	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	5	84	theme	cardiac	1098:1104	arg1	function					1116:1123	deteriorated cardiac diastolic function	1085:1123	deteriorated cardiac diastolic function	1085:1123	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	0	85	from	injury	137:142	arg1	type					147:150	type I diabetic rats	147:166	type I diabetic rats	147:166	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	10	86	theme	protein	2389:2395	arg1	SNAP29					2308:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	86	theme	protein	2389:2395	arg1	complex					2407:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex	2331:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2331:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	4	87	theme	microtubule‑associated	770:791	arg1	chain					809:813	microtubule‑associated protein 1 light chain	770:813	microtubule‑associated protein 1 light chain 3α II/I	770:821	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	87	theme	microtubule‑associated	770:791	arg1	markers					762:768	the autophagy markers	748:768	the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited,	748:879	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	5	88	theme	fibrosis	1382:1389	arg1	accumulation					1391:1402	interstitial fibrosis accumulation	1369:1402	interstitial fibrosis accumulation	1369:1402	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	8	89	theme	SNAP29	1889:1894	arg1	modification					1873:1884	O‑GlcNAc modification	1864:1884	O‑GlcNAc modification of SNAP29	1864:1894	Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux.
30221662	2	90	theme	diabetic	537:544	arg1	injury					557:562	diabetic myocardial injury	537:562	diabetic myocardial injury	537:562	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	10	91	theme	‑vesicle‑associated	2360:2378	arg1	SNAP29					2308:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	the O‑GlcNAc‑modified substrate protein SNAP29	2268:2313	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	10	91	theme	‑vesicle‑associated	2360:2378	arg1	complex					2407:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex	2331:2413	an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression	2331:2440	Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression.
30221662	5	92	theme	cardiomyocyte	1327:1339	arg1	disorganization					1341:1355	cardiomyocyte disorganization	1327:1355	cardiomyocyte disorganization	1327:1355	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	6	93	theme	fructose‑6‑phosphate	1474:1493	arg1	isomerizing					1512:1522	glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1	1462:1524	glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1	1462:1524	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	5	94	theme	peak	1180:1183	arg1	ratio					1232:1236	peak velocity/atrial contraction flow peak velocity ratio	1180:1236	peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1180:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	1	95	theme	β‑N‑acetylglucosamine	182:202	arg1	modification					215:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated.
30221662	11	96	theme	complex	2634:2640	arg1	formation					2642:2650	SNAP29‑STX17‑VAMP8 complex formation	2615:2650	SNAP29‑STX17‑VAMP8 complex formation	2615:2650	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	9	97	theme	initial	2174:2180	arg1	stage					2182:2186	the initial stage	2170:2186	the initial stage of autophagy	2170:2199	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	6	98	theme	aminotransferase	1495:1510	arg1	isomerizing					1512:1522	glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1	1462:1524	glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1	1462:1524	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	5	99	theme	contraction	1201:1211	arg1	ratio					1232:1236	peak velocity/atrial contraction flow peak velocity ratio	1180:1236	peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1180:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	0	100	dep	type	147:150	arg1	rats					163:166	diabetic rats	154:166	type I diabetic rats	147:166	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	7	101	theme	high	1691:1694	arg1	25 mM					1705:1709	25 mM	1705:1709	25 mM	1705:1709	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	7	101	theme	high	1691:1694	arg1	In vitro					1681:1688	In vitro	1681:1688	In vitro	1681:1688	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	7	101	theme	high	1691:1694	arg1	glucose					1696:1702	high glucose	1691:1702	high glucose (25 mM)	1691:1710	In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs).
30221662	6	102	theme	glucosamine	1462:1472	arg1	isomerizing					1512:1522	glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1	1462:1524	glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1	1462:1524	By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function.
30221662	5	103	theme	increased	1145:1153	arg1	ventricular					1160:1170	an increased left ventricular	1142:1170	an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1142:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	5	104	theme	thiamet	987:993	arg1	inhibitor					976:984	the selective O‑GlcNAcase inhibitor	950:984	the selective O‑GlcNAcase inhibitor	950:984	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	5	104	theme	thiamet	987:993	arg1	G					995:995	thiamet G	987:995	thiamet G	987:995	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	2	105	theme	O‑GlcNAc‑modified	472:488	arg1	protein					514:520	O‑GlcNAc‑modified synaptosomal‑associated protein 29	472:523	O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury	472:562	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	2	105	theme	O‑GlcNAc‑modified	472:488	arg1	SNAP29					526:531	SNAP29	526:531	SNAP29	526:531	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	2	106	theme	study	408:412	arg1	purpose					385:391	The purpose	381:391	The purpose of the present study	381:412	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	0	107	theme	autophagy-mediated	34:51	arg1	degradation					53:63	autophagy-mediated degradation	34:63	autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex	34:108	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	4	108	dep	markers	762:768	arg1	chain					809:813	microtubule‑associated protein 1 light chain	770:813	microtubule‑associated protein 1 light chain 3α II/I	770:821	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	108	dep	markers	762:768	arg1	markers					762:768	the autophagy markers	748:768	the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited,	748:879	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	4	108	dep	markers	762:768	arg1	P62					827:829	P62	827:829	P62	827:829	Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction.
30221662	2	109	theme	autophagy	459:467	arg1	regulation					445:454	the molecular regulation	431:454	the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury	431:562	The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury.
30221662	11	110	dep	inhibits	2606:2613	arg1	exacerbating					2705:2716	exacerbating	2705:2716	exacerbating myocardial injury in type I diabetic rats	2705:2758	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	11	110	dep	inhibits	2606:2613	arg1	inhibiting					2661:2670	inhibiting	2661:2670	inhibiting the degradation of autophagy	2661:2699	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	1	111	link	O‑linked	173:180	arg1	modification					215:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification	169:226	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated.
30221662	0	112	theme	disturbed	73:81	arg1	complex					102:108	the disturbed SNAP29-STX17-VAMP8 complex	69:108	the disturbed SNAP29-STX17-VAMP8 complex	69:108	O-GlcNAc-modified SNAP29 inhibits autophagy-mediated degradation via the disturbed SNAP29-STX17-VAMP8 complex and exacerbates myocardial injury in type I diabetic rats.
30221662	5	113	theme	peak	1218:1221	arg1	ratio					1232:1236	peak velocity/atrial contraction flow peak velocity ratio	1180:1236	peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography	1180:1262	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	9	114	theme	hairpin	1963:1969	arg1	interference					1975:1986	the short hairpin RNA interference	1953:1986	the short hairpin RNA interference	1953:1986	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	5	115	theme	modification	1030:1041	arg1	level					1012:1016	the level	1008:1016	the level	1008:1016	Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation.
30221662	9	116	theme	interference	1975:1986	arg1	application					1938:1948	The application	1934:1948	The application of the short hairpin RNA interference	1934:1986	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	1	117	theme	myocardial	271:280	arg1	injury					282:287	diabetic myocardial injury	262:287	diabetic myocardial injury	262:287	The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated.
30221662	11	118	from	injury	2729:2734	arg1	type					2739:2742	type I diabetic rats	2739:2758	type I diabetic rats	2739:2758	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	9	119	theme	membrane	2008:2015	arg1	LAMP2					2026:2030	LAMP2	2026:2030	LAMP2	2026:2030	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	9	119	theme	membrane	2008:2015	arg1	protein					2017:2023	membrane protein	2008:2023	membrane protein (LAMP2)	2008:2031	The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy.
30221662	11	120	theme	diabetic	2746:2753	arg1	rats					2755:2758	diabetic rats	2746:2758	type I diabetic rats	2739:2758	The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.
30221662	3	121	theme	rat	567:569	arg1	model					571:575	A rat model	565:575	A rat model of type I diabetes	565:594	A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg).
29875238	2	0	theme	receptor	338:345	arg1	α-dystroglycan					347:360	the ubiquitous receptor α-dystroglycan	323:360	the ubiquitous receptor α-dystroglycan (αDG)	323:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	2	0	theme	receptor	338:345	arg1	αDG					363:365	αDG	363:365	αDG	363:365	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	9	1	theme	IgV	1619:1621	arg1	pocket					1638:1643	the IgV PtdSer-binding pocket	1615:1643	the IgV PtdSer-binding pocket of TIM-1	1615:1652	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	1	2	theme	responsible	108:118	arg1	arenavirus					97:106	an Old World arenavirus	84:106	an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year	84:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	1	2	theme	responsible	108:118	arg1	virus					68:72	Lassa virus	62:72	Lassa virus (LASV)	62:79	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	4	3	theme	C-type	585:590	arg1	receptors					599:607	C-type lectin receptors	585:607	the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors	510:607	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	15	4	theme	PtdSer	2598:2603	arg1	receptors					2605:2613	PtdSer receptors	2598:2613	PtdSer receptors for virus uptake	2598:2630	Our studies shed light on LASV receptor utilization and explain why previous studies performed with α-DG-expressing cells did not find that LASV pseudovirions utilize PtdSer receptors for virus uptake.
29875238	13	5	theme	GP-pseudotyped	2108:2121	arg1	viruses					2123:2129	LASV GP-pseudotyped viruses	2103:2129	LASV GP-pseudotyped viruses	2103:2129	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	14	6	theme	cell	2399:2402	arg1	receptor					2412:2419	the high-affinity cell surface receptor	2381:2419	the high-affinity cell surface receptor for LASV	2381:2428	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	6	theme	cell	2399:2402	arg1	α-dystroglycan					2359:2372	appropriately glycosylated α-dystroglycan	2332:2372	appropriately glycosylated α-dystroglycan (αDG)	2332:2378	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	9	7	theme	TIM-1	1648:1652	arg1	pocket					1638:1643	the IgV PtdSer-binding pocket	1615:1643	the IgV PtdSer-binding pocket of TIM-1	1615:1652	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	7	8	theme	domain-binding	1079:1092	arg1	antibody					1105:1112	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	2	9	theme	O-linked	295:302	arg1	glycans					304:310	glycosyltransferase LARGE-modified O-linked glycans	260:310	glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG)	260:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	12	10	theme	embedded	1925:1932	arg1	binding					1907:1913	the binding	1903:1913	the binding of PtdSer embedded in the viral envelope	1903:1954	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	7	11	theme	TIM-1	1069:1073	arg1	antibody					1105:1112	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	2	12	theme	glycosyltransferase	260:278	arg1	glycans					304:310	glycosyltransferase LARGE-modified O-linked glycans	260:310	glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG)	260:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	11	13	theme	hepatitis	1780:1788	arg1	virus					1792:1796	hepatitis C virus	1780:1796	hepatitis C virus	1780:1796	Most recently, hepatitis C virus and Zika virus have been added to a growing list.
29875238	5	14	theme	glycoprotein	712:723	arg1	entry					749:753	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	4	15	dep	along	574:578	arg1	with					580:583	with	580:583	with	580:583	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	8	16	theme	chimeric	1280:1287	arg1	protein					1295:1301	a chimeric TIM-1 protein	1278:1301	a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1278:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	8	16	theme	chimeric	1280:1287	arg1	entry					1271:1275	entry	1271:1275	entry	1271:1275	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	10	17	theme	enveloped	1746:1754	arg1	viruses					1756:1762	many enveloped viruses	1741:1762	many enveloped viruses	1741:1762	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	5	18	gly	glycoprotein	712:723	arg1	GP					726:727	GP	726:727	GP	726:727	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	5	18	gly	glycoprotein	712:723	arg1	glycoprotein					712:723	LASV glycoprotein	707:723	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	14	19	theme	PtdSer	2283:2288	arg1	TIM-1					2299:2303	the PtdSer receptor TIM-1	2279:2303	the PtdSer receptor TIM-1	2279:2303	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	2	20	with	interactions	242:253	arg1	glycans					304:310	glycosyltransferase LARGE-modified O-linked glycans	260:310	glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG)	260:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	2	21	theme	types	221:225	arg1	variety					205:211	a variety	203:211	a variety of cell types	203:225	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	2	21	theme	types	221:225	arg1	types					221:225	cell types	216:225	cell types	216:225	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	6	22	theme	PtdSer-binding	1000:1013	arg1	pocket					1015:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	To investigate the mechanism by which TIM-1 mediates enhancement of entry, we demonstrate that mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket abrogated transduction.
29875238	13	23	theme	GP-independent	2005:2018	arg1	mechanism					2026:2034	This GP-independent entry mechanism	2000:2034	This GP-independent entry mechanism	2000:2034	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	5	24	theme	Vero	804:807	arg1	cells					809:813	αDG-knocked-out HEK 293T and wild-type (WT) Vero cells	760:813	cells	809:813	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	1	25	from	infections	149:158	arg1	Africa					168:173	Africa	168:173	Africa	168:173	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	13	26	theme	293T	2210:2213	arg1	cells					2215:2219	HEK 293T cells	2206:2219	HEK 293T cells	2206:2219	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	6	27	theme	IgV	989:991	arg1	pocket					1015:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	To investigate the mechanism by which TIM-1 mediates enhancement of entry, we demonstrate that mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket abrogated transduction.
29875238	8	28	theme	proline-rich	1324:1335	arg1	PRR					1345:1347	PRR	1345:1347	PRR	1345:1347	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	8	28	theme	proline-rich	1324:1335	arg1	region					1337:1342	the proline-rich region	1320:1342	the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1320:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	5	29	theme	αDG-knocked-out	760:774	arg1	293T					780:783	αDG-knocked-out HEK 293T and wild-type (WT) Vero cells	760:813	293T	780:783	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	12	30	theme	PtdSer	1848:1853	arg1	receptors					1855:1863	PtdSer receptors	1848:1863	PtdSer receptors	1848:1863	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	1	31	from	thousands	136:144	arg1	Africa					168:173	Africa	168:173	Africa	168:173	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	15	32	theme	receptor	2462:2469	arg1	utilization					2471:2481	LASV receptor utilization	2457:2481	LASV receptor utilization	2457:2481	Our studies shed light on LASV receptor utilization and explain why previous studies performed with α-DG-expressing cells did not find that LASV pseudovirions utilize PtdSer receptors for virus uptake.
29875238	9	33	theme	functional	1507:1516	arg1	αDG					1518:1520	a functional αDG	1505:1520	a functional αDG	1505:1520	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	13	34	from	enhancement	2191:2201	arg1	cells					2215:2219	HEK 293T cells	2206:2219	HEK 293T cells	2206:2219	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	3	35	theme	LASV	414:417	arg1	infection					419:427	LASV infection	414:427	LASV infection	414:427	However, cells lacking αDG are permissive to LASV infection, suggesting that alternative receptors exist.
29875238	5	36	theme	-pseudotyped	729:740	arg1	entry					749:753	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	4	37	dep	receptors	550:558	arg1	receptors					550:558	the phosphatidylserine (PtdSer)-binding receptors	510:558	the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors	510:607	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	4	37	dep	receptors	550:558	arg1	Tyro3					568:572	Tyro3	568:572	Tyro3	568:572	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	4	37	dep	receptors	550:558	arg1	Axl					560:562	Axl	560:562	Axl	560:562	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	5	38	theme	HEK	776:778	arg1	293T					780:783	αDG-knocked-out HEK 293T and wild-type (WT) Vero cells	760:813	293T	780:783	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	8	39	theme	murine	1355:1360	arg1	virus					1371:1375	murine leukemia virus	1355:1375	murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1355:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	13	40	theme	PtdSer	2175:2180	arg1	enhancement					2191:2201	PtdSer receptor enhancement	2175:2201	PtdSer receptor enhancement in HEK 293T cells	2175:2219	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	4	41	theme	-binding	541:548	arg1	receptors					550:558	the phosphatidylserine (PtdSer)-binding receptors	510:558	the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors	510:607	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	4	41	theme	-binding	541:548	arg1	Tyro3					568:572	Tyro3	568:572	Tyro3	568:572	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	4	41	theme	-binding	541:548	arg1	Axl					560:562	Axl	560:562	Axl	560:562	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	8	42	theme	virus	1371:1375	arg1	Env					1387:1389	Env	1387:1389	Env	1387:1389	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	8	42	theme	virus	1371:1375	arg1	envelope					1377:1384	murine leukemia virus envelope	1355:1384	murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1355:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	0	43	theme	Dystroglycan-Independent	15:38	arg1	Entry					40:44	Dystroglycan-Independent Entry	15:44	Dystroglycan-Independent Entry of Lassa Virus	15:59	TIM-1 Mediates Dystroglycan-Independent Entry of Lassa Virus.
29875238	12	44	from	embedded	1925:1932	arg1	envelope					1947:1954	the viral envelope	1937:1954	the viral envelope	1937:1954	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	1	45	theme	Old	87:89	arg1	arenavirus					97:106	an Old World arenavirus	84:106	an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year	84:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	1	45	theme	Old	87:89	arg1	virus					68:72	Lassa virus	62:72	Lassa virus (LASV)	62:79	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	9	46	theme	LASV	1551:1554	arg1	particles					1568:1576	LASV pseudoviral particles	1551:1576	LASV pseudoviral particles	1551:1576	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	12	47	theme	viral	1941:1945	arg1	envelope					1947:1954	the viral envelope	1937:1954	the viral envelope	1937:1954	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	14	48	theme	surface	2404:2410	arg1	receptor					2412:2419	the high-affinity cell surface receptor	2381:2419	the high-affinity cell surface receptor for LASV	2381:2428	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	48	theme	surface	2404:2410	arg1	α-dystroglycan					2359:2372	appropriately glycosylated α-dystroglycan	2332:2372	appropriately glycosylated α-dystroglycan (αDG)	2332:2378	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	2	49	theme	ubiquitous	327:336	arg1	α-dystroglycan					347:360	the ubiquitous receptor α-dystroglycan	323:360	the ubiquitous receptor α-dystroglycan (αDG)	323:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	2	49	theme	ubiquitous	327:336	arg1	αDG					363:365	αDG	363:365	αDG	363:365	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	5	50	theme	wild-type	789:797	arg1	cells					809:813	αDG-knocked-out HEK 293T and wild-type (WT) Vero cells	760:813	cells	809:813	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	9	51	theme	particles	1568:1576	arg1	entry					1542:1546	the entry	1538:1546	the entry of LASV pseudoviral particles	1538:1576	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	10	52	theme	PtdSer	1665:1670	arg1	receptors					1672:1680	IMPORTANCE PtdSer receptors	1654:1680	IMPORTANCE PtdSer receptors	1654:1680	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	10	52	theme	PtdSer	1665:1670	arg1	TIM-1					1691:1695	TIM-1	1691:1695	TIM-1	1691:1695	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	4	53	theme	lectin	592:597	arg1	receptors					599:607	C-type lectin receptors	585:607	the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors	510:607	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	15	54	theme	α-DG-expressing	2531:2545	arg1	cells					2547:2551	α-DG-expressing cells	2531:2551	α-DG-expressing cells	2531:2551	Our studies shed light on LASV receptor utilization and explain why previous studies performed with α-DG-expressing cells did not find that LASV pseudovirions utilize PtdSer receptors for virus uptake.
29875238	9	55	theme	virions	1602:1608	arg1	interactions					1586:1597	interactions	1586:1597	interactions of virions with the IgV PtdSer-binding pocket of TIM-1	1586:1652	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	14	56	theme	glycosylated	2346:2357	arg1	receptor					2412:2419	the high-affinity cell surface receptor	2381:2419	the high-affinity cell surface receptor for LASV	2381:2428	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	56	theme	glycosylated	2346:2357	arg1	αDG					2375:2377	αDG	2375:2377	αDG	2375:2377	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	56	theme	glycosylated	2346:2357	arg1	α-dystroglycan					2359:2372	appropriately glycosylated α-dystroglycan	2332:2372	appropriately glycosylated α-dystroglycan (αDG)	2332:2378	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	57	gly	glycosylated	2346:2357	arg1	receptor					2412:2419	the high-affinity cell surface receptor	2381:2419	the high-affinity cell surface receptor for LASV	2381:2428	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	57	gly	glycosylated	2346:2357	arg1	αDG					2375:2377	αDG	2375:2377	αDG	2375:2377	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	57	gly	glycosylated	2346:2357	arg1	α-dystroglycan					2359:2372	appropriately glycosylated α-dystroglycan	2332:2372	appropriately glycosylated α-dystroglycan (αDG)	2332:2378	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	10	58	theme	critical	1714:1721	arg1	factors					1729:1735	critical entry factors	1714:1735	critical entry factors for many enveloped viruses	1714:1762	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	15	59	theme	previous	2499:2506	arg1	studies					2508:2514	previous studies	2499:2514	previous studies performed with α-DG-expressing cells	2499:2551	Our studies shed light on LASV receptor utilization and explain why previous studies performed with α-DG-expressing cells did not find that LASV pseudovirions utilize PtdSer receptors for virus uptake.
29875238	13	60	theme	LASV	2103:2106	arg1	viruses					2123:2129	LASV GP-pseudotyped viruses	2103:2129	LASV GP-pseudotyped viruses	2103:2129	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	12	61	from	envelope	1947:1954	arg1	embedded					1925:1932	embedded	1925:1932	embedded	1925:1932	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	9	62	theme	PtdSer-binding	1623:1636	arg1	pocket					1638:1643	the IgV PtdSer-binding pocket	1615:1643	the IgV PtdSer-binding pocket of TIM-1	1615:1652	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	11	63	theme	Zika	1802:1805	arg1	virus					1807:1811	Zika virus	1802:1811	Zika virus	1802:1811	Most recently, hepatitis C virus and Zika virus have been added to a growing list.
29875238	7	64	theme	monoclonal	1094:1103	arg1	antibody					1105:1112	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	1	65	theme	infections	149:158	arg1	thousands					136:144	thousands	136:144	thousands of infections in West Africa every year	136:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	0	66	theme	Virus	55:59	arg1	Entry					40:44	Dystroglycan-Independent Entry	15:44	Dystroglycan-Independent Entry of Lassa Virus	15:59	TIM-1 Mediates Dystroglycan-Independent Entry of Lassa Virus.
29875238	2	67	attach	present	312:318	arg2	glycans					304:310	glycosyltransferase LARGE-modified O-linked glycans	260:310	glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG)	260:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	2	67	attach	present	312:318	arg1	α-dystroglycan					347:360	the ubiquitous receptor α-dystroglycan	323:360	the ubiquitous receptor α-dystroglycan (αDG)	323:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	2	67	attach	present	312:318	arg1	αDG					363:365	αDG	363:365	αDG	363:365	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	5	68	dep	wild-type	789:797	arg1	WT					800:801	WT	800:801	WT	800:801	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	8	69	theme	other	1238:1242	arg1	viruses					1244:1250	other viruses	1238:1250	other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1238:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	7	70	theme	IgV	1075:1077	arg1	antibody					1105:1112	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	10	71	theme	many	1741:1744	arg1	viruses					1756:1762	many enveloped viruses	1741:1762	many enveloped viruses	1741:1762	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	8	72	from	envelope	1377:1384	arg1	PRR					1345:1347	PRR	1345:1347	PRR	1345:1347	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	8	72	from	envelope	1377:1384	arg1	region					1337:1342	the proline-rich region	1320:1342	the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1320:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	5	73	theme	appropriate	842:852	arg1	glycosylation					854:866	appropriate glycosylation	842:866	appropriate glycosylation	842:866	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	7	74	theme	human	1063:1067	arg1	antibody					1105:1112	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	the human TIM-1 IgV domain-binding monoclonal antibody ARD5	1059:1117	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	2	75	theme	LARGE-modified	280:293	arg1	glycans					304:310	glycosyltransferase LARGE-modified O-linked glycans	260:310	glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG)	260:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	15	76	theme	LASV	2571:2574	arg1	pseudovirions					2576:2588	LASV pseudovirions	2571:2588	LASV pseudovirions	2571:2588	Our studies shed light on LASV receptor utilization and explain why previous studies performed with α-DG-expressing cells did not find that LASV pseudovirions utilize PtdSer receptors for virus uptake.
29875238	12	77	theme	PtdSer	1918:1923	arg1	binding					1907:1913	the binding	1903:1913	the binding of PtdSer embedded in the viral envelope	1903:1954	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	5	78	theme	LASV	707:710	arg1	GP					726:727	GP	726:727	GP	726:727	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	5	78	theme	LASV	707:710	arg1	glycoprotein					712:723	LASV glycoprotein	707:723	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	12	79	theme	enveloped	1877:1885	arg1	viruses					1887:1893	enveloped viruses	1877:1893	enveloped viruses	1877:1893	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	6	80	theme	entry	937:941	arg1	enhancement					922:932	enhancement	922:932	enhancement of entry	922:941	To investigate the mechanism by which TIM-1 mediates enhancement of entry, we demonstrate that mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket abrogated transduction.
29875238	8	81	theme	competent	1430:1438	arg1	receptor					1440:1447	a competent receptor	1428:1447	a competent receptor	1428:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	14	82	dep	α-dystroglycan	2359:2372	arg1	absence					2321:2327	absence	2321:2327	absence	2321:2327	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	82	dep	α-dystroglycan	2359:2372	arg1	the					2317:2319	the	2317:2319	the	2317:2319	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	11	83	theme	C	1790:1790	arg1	virus					1792:1796	hepatitis C virus	1780:1796	hepatitis C virus	1780:1796	Most recently, hepatitis C virus and Zika virus have been added to a growing list.
29875238	5	84	theme	PtdSer	674:679	arg1	TIM-1					691:695	TIM-1	691:695	TIM-1	691:695	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	5	84	theme	PtdSer	674:679	arg1	receptor					681:688	another PtdSer receptor	666:688	another PtdSer receptor	666:688	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	13	85	theme	viruses	2090:2096	arg1	entry					2067:2071	the entry	2063:2071	the entry of all enveloped viruses	2063:2096	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	1	86	theme	World	91:95	arg1	arenavirus					97:106	an Old World arenavirus	84:106	an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year	84:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	1	86	theme	World	91:95	arg1	virus					68:72	Lassa virus	62:72	Lassa virus (LASV)	62:79	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	14	87	theme	receptor	2290:2297	arg1	TIM-1					2299:2303	the PtdSer receptor TIM-1	2279:2303	the PtdSer receptor TIM-1	2279:2303	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	2	88	link	O-linked	295:302	arg1	glycans					304:310	glycosyltransferase LARGE-modified O-linked glycans	260:310	glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG)	260:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	0	89	theme	Lassa	49:53	arg1	Virus					55:59	Lassa Virus	49:59	Lassa Virus	49:59	TIM-1 Mediates Dystroglycan-Independent Entry of Lassa Virus.
29875238	6	90	theme	pocket	1015:1020	arg1	mutagenesis					964:974	mutagenesis	964:974	mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket	964:1020	To investigate the mechanism by which TIM-1 mediates enhancement of entry, we demonstrate that mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket abrogated transduction.
29875238	8	91	theme	TIM-1	1289:1293	arg1	protein					1295:1301	a chimeric TIM-1 protein	1278:1301	a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1278:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	8	91	theme	TIM-1	1289:1293	arg1	entry					1271:1275	entry	1271:1275	entry	1271:1275	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	5	92	theme	virion	742:747	arg1	entry					749:753	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	LASV glycoprotein (GP)-pseudotyped virion entry	707:753	Here, we demonstrate that another PtdSer receptor, TIM-1, mediates LASV glycoprotein (GP)-pseudotyped virion entry into αDG-knocked-out HEK 293T and wild-type (WT) Vero cells, which express αDG lacking appropriate glycosylation.
29875238	2	93	theme	cell	216:219	arg1	types					221:225	cell types	216:225	cell types	216:225	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	1	94	from	Africa	168:173	arg1	thousands					136:144	thousands	136:144	thousands of infections in West Africa every year	136:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	13	95	theme	HEK	2206:2208	arg1	cells					2215:2219	HEK 293T cells	2206:2219	HEK 293T cells	2206:2219	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	6	96	theme	domain	993:998	arg1	pocket					1015:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	To investigate the mechanism by which TIM-1 mediates enhancement of entry, we demonstrate that mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket abrogated transduction.
29875238	12	97	theme	GP-independent	1974:1987	arg1	them					1966:1969	them	1966:1969	them	1966:1969	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	12	97	theme	GP-independent	1974:1987	arg1	receptors					1989:1997	GP-independent receptors	1974:1997	GP-independent receptors	1974:1997	PtdSer receptors engage with enveloped viruses through the binding of PtdSer embedded in the viral envelope, defining them as GP-independent receptors.
29875238	13	98	theme	entry	2020:2024	arg1	mechanism					2026:2034	This GP-independent entry mechanism	2000:2034	This GP-independent entry mechanism	2000:2034	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	1	99	theme	thousands	136:144	arg1	hundreds					124:131	hundreds	124:131	hundreds of thousands of infections in West Africa every year	124:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	6	100	theme	TIM-1	983:987	arg1	pocket					1015:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	the TIM-1 IgV domain PtdSer-binding pocket	979:1020	To investigate the mechanism by which TIM-1 mediates enhancement of entry, we demonstrate that mutagenesis of the TIM-1 IgV domain PtdSer-binding pocket abrogated transduction.
29875238	14	101	theme	LASV	2248:2251	arg1	pseudovirions					2253:2265	LASV pseudovirions	2248:2265	LASV pseudovirions	2248:2265	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	1	102	theme	Lassa	62:66	arg1	LASV					75:78	LASV	75:78	LASV	75:78	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	1	102	theme	Lassa	62:66	arg1	virus					68:72	Lassa virus	62:72	Lassa virus (LASV)	62:79	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	1	102	theme	Lassa	62:66	arg1	arenavirus					97:106	an Old World arenavirus	84:106	an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year	84:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	10	103	theme	entry	1723:1727	arg1	factors					1729:1735	critical entry factors	1714:1735	critical entry factors for many enveloped viruses	1714:1762	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	2	104	theme	present	312:318	arg1	glycans					304:310	glycosyltransferase LARGE-modified O-linked glycans	260:310	glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG)	260:366	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	9	105	theme	αDG	1518:1520	arg1	absence					1494:1500	the absence	1490:1500	the absence of a functional αDG	1490:1520	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	4	106	theme	Previous	475:482	arg1	studies					484:490	Previous studies	475:490	Previous studies	475:490	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	7	107	theme	dose-dependent	1178:1191	arg1	manner					1193:1198	a dose-dependent manner	1176:1198	a dose-dependent manner	1176:1198	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	15	108	theme	LASV	2457:2460	arg1	utilization					2471:2481	LASV receptor utilization	2457:2481	LASV receptor utilization	2457:2481	Our studies shed light on LASV receptor utilization and explain why previous studies performed with α-DG-expressing cells did not find that LASV pseudovirions utilize PtdSer receptors for virus uptake.
29875238	11	109	theme	growing	1834:1840	arg1	list					1842:1845	a growing list	1832:1845	a growing list	1832:1845	Most recently, hepatitis C virus and Zika virus have been added to a growing list.
29875238	13	110	theme	receptor	2182:2189	arg1	enhancement					2191:2201	PtdSer receptor enhancement	2175:2201	PtdSer receptor enhancement in HEK 293T cells	2175:2219	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	8	111	theme	leukemia	1362:1369	arg1	virus					1371:1375	murine leukemia virus	1355:1375	murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor	1355:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29875238	3	112	theme	alternative	446:456	arg1	receptors					458:466	alternative receptors	446:466	alternative receptors	446:466	However, cells lacking αDG are permissive to LASV infection, suggesting that alternative receptors exist.
29875238	7	113	theme	LASV	1165:1168	arg1	GP					1170:1171	LASV GP	1165:1171	LASV GP	1165:1171	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	1	114	dep	Africa	168:173	arg1	year					181:184	every year	175:184	West Africa every year	163:184	Lassa virus (LASV) is an Old World arenavirus responsible for hundreds of thousands of infections in West Africa every year.
29875238	14	115	theme	high-affinity	2385:2397	arg1	receptor					2412:2419	the high-affinity cell surface receptor	2381:2419	the high-affinity cell surface receptor for LASV	2381:2428	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	14	115	theme	high-affinity	2385:2397	arg1	α-dystroglycan					2359:2372	appropriately glycosylated α-dystroglycan	2332:2372	appropriately glycosylated α-dystroglycan (αDG)	2332:2378	Here, we demonstrate that LASV pseudovirions can utilize the PtdSer receptor TIM-1 but only in the absence of appropriately glycosylated α-dystroglycan (αDG), the high-affinity cell surface receptor for LASV.
29875238	15	116	theme	virus	2619:2623	arg1	uptake					2625:2630	virus uptake	2619:2630	virus uptake	2619:2630	Our studies shed light on LASV receptor utilization and explain why previous studies performed with α-DG-expressing cells did not find that LASV pseudovirions utilize PtdSer receptors for virus uptake.
29875238	7	117	theme	pseudovirions	1143:1155	arg1	transduction					1127:1138	transduction	1127:1138	transduction of pseudovirions bearing LASV GP	1127:1171	Furthermore, the human TIM-1 IgV domain-binding monoclonal antibody ARD5 blocked transduction of pseudovirions bearing LASV GP in a dose-dependent manner.
29875238	9	118	theme	pseudoviral	1556:1566	arg1	particles					1568:1576	LASV pseudoviral particles	1551:1576	LASV pseudoviral particles	1551:1576	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	2	119	theme	LASV	187:190	arg1	entry					192:196	LASV entry	187:196	LASV entry into a variety of cell types	187:225	LASV entry into a variety of cell types is mediated by interactions with glycosyltransferase LARGE-modified O-linked glycans present on the ubiquitous receptor α-dystroglycan (αDG).
29875238	13	120	theme	enveloped	2080:2088	arg1	viruses					2090:2096	all enveloped viruses	2076:2096	all enveloped viruses	2076:2096	This GP-independent entry mechanism should effectively mediate the entry of all enveloped viruses, yet LASV GP-pseudotyped viruses were previously found to be unresponsive to PtdSer receptor enhancement in HEK 293T cells.
29875238	10	121	theme	IMPORTANCE	1654:1663	arg1	receptors					1672:1680	IMPORTANCE PtdSer receptors	1654:1680	IMPORTANCE PtdSer receptors	1654:1680	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	10	121	theme	IMPORTANCE	1654:1663	arg1	TIM-1					1691:1695	TIM-1	1691:1695	TIM-1	1691:1695	IMPORTANCE PtdSer receptors, such as TIM-1, are emerging as critical entry factors for many enveloped viruses.
29875238	4	122	theme	αDG-independent	617:631	arg1	entry					633:637	αDG-independent entry	617:637	αDG-independent entry	617:637	Previous studies demonstrated that the phosphatidylserine (PtdSer)-binding receptors Axl and Tyro3 along with C-type lectin receptors mediate αDG-independent entry.
29875238	9	123	with	virions	1602:1608	arg1	pocket					1638:1643	the IgV PtdSer-binding pocket	1615:1643	the IgV PtdSer-binding pocket of TIM-1	1615:1652	These studies provide evidence that, in the absence of a functional αDG, TIM-1 mediates the entry of LASV pseudoviral particles through interactions of virions with the IgV PtdSer-binding pocket of TIM-1.
29875238	8	124	theme	mucin-like	1400:1409	arg1	domain					1411:1416	the mucin-like domain	1396:1416	the mucin-like domain served as a competent receptor	1396:1447	Finally, as we showed previously for other viruses that use TIM-1 for entry, a chimeric TIM-1 protein that substitutes the proline-rich region (PRR) from murine leukemia virus envelope (Env) for the mucin-like domain served as a competent receptor.
29454317	2	0	theme	O-linked	353:360	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	0	theme	O-linked	353:360	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	0	theme	O-linked	353:360	arg1	counterpart					463:473	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	6	1	theme	BC	1134:1135	arg1	cells					1137:1141	BCG-challenged BC cells	1119:1141	BCG-challenged BC cells	1119:1141	Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.
29454317	11	2	theme	potential	1903:1911	arg1	impact					1913:1918	a potential impact	1901:1918	a potential impact on BC biology and patient's response to BCG	1901:1962	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	11	3	theme	stronger	1802:1809	arg1	response					1822:1829	a stronger macrophage response	1800:1829	a stronger macrophage response	1800:1829	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	3	4	dep	METHODS	596:602	arg1	line					639:642	The human bladder cancer (BC) cell line HT1376	604:649	The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen	604:683	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	10	5	theme	BCG	1576:1578	arg1	challenge					1580:1588	BCG challenge	1576:1588	BCG challenge	1576:1588	After BCG challenge, the transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation than that of HT1376T cells.
29454317	5	6	theme	multiplex	1004:1012	arg1	assay					1027:1031	multiplex immune-beads assay	1004:1031	multiplex immune-beads assay	1004:1031	Whole gene expression was studied by microarray technology, cytokine secretion was measured by multiplex immune-beads assay.
29454317	6	7	theme	Human	1034:1038	arg1	macrophages					1040:1050	Human macrophages	1034:1050	Human macrophages derived from blood monocytes	1034:1079	Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.
29454317	10	8	theme	HT1376sT	1612:1619	arg1	cells					1621:1625	HT1376sT cells	1612:1625	HT1376sT cells	1612:1625	After BCG challenge, the transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation than that of HT1376T cells.
29454317	3	9	theme	empty	747:751	arg1	vector					753:758	an empty vector	744:758	an empty vector	744:758	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	1	10	theme	invasive	235:242	arg1	NMIBC					260:264	NMIBC	260:264	NMIBC	260:264	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	10	theme	invasive	235:242	arg1	cancer					252:257	non-muscle invasive bladder cancer	224:257	non-muscle invasive bladder cancer (NMIBC)	224:265	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	3	11	dep	lines	779:783	arg1	HT1376sT					785:792	HT1376sT	785:792	HT1376sT	785:792	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	3	11	dep	lines	779:783	arg1	lines					779:783	the cell lines HT1376sT and HT1376T	770:804	the cell lines HT1376sT and HT1376T	770:804	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	3	11	dep	lines	779:783	arg1	HT1376T					798:804	HT1376T	798:804	HT1376T	798:804	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	11	12	from	replacement	1747:1757	arg1	cells					1787:1791	BCG challenged-BC cancer cells	1762:1791	BCG challenged-BC cancer cells	1762:1791	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	3	13	theme	cancer	622:627	arg1	line					639:642	The human bladder cancer (BC) cell line HT1376	604:649	The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen	604:683	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	11	14	from	impact	1913:1918	arg1	response					1948:1955	patient's response	1938:1955	patient's response to BCG	1938:1962	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	11	14	from	impact	1913:1918	arg1	biology					1926:1932	BC biology	1923:1932	BC biology	1923:1932	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	0	15	theme	bladder	61:67	arg1	cells					76:80	bladder cancer cells	61:80	bladder cancer cells expressing sialyltransferase ST3GAL1	61:117	Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.
29454317	3	16	theme	human	608:612	arg1	line					639:642	The human bladder cancer (BC) cell line HT1376	604:649	The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen	604:683	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	11	17	theme	gene	1845:1848	arg1	expression					1850:1859	the gene expression	1841:1859	the gene expression towards genomic instability	1841:1887	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	2	18	theme	sialyl-T	498:505	arg1	counterpart					463:473	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	18	theme	sialyl-T	498:505	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	18	theme	sialyl-T	498:505	arg1	Siaα2,3Galβ1,3GalNAc					476:495	Siaα2,3Galβ1,3GalNAc	476:495	Siaα2,3Galβ1,3GalNAc	476:495	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	11	19	theme	cancer	1780:1785	arg1	cells					1787:1791	BCG challenged-BC cancer cells	1762:1791	BCG challenged-BC cancer cells	1762:1791	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	7	20	theme	HT1376sT	1186:1193	arg1	cells					1195:1199	BCG-challenged HT1376sT cells	1171:1199	BCG-challenged HT1376sT cells	1171:1199	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	2	21	dep	carbohydrates	362:374	arg1	counterpart					463:473	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	21	dep	carbohydrates	362:374	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	21	dep	carbohydrates	362:374	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	21	dep	carbohydrates	362:374	arg1	Siaα2,3Galβ1,3GalNAc					476:495	Siaα2,3Galβ1,3GalNAc	476:495	Siaα2,3Galβ1,3GalNAc	476:495	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	11	22	theme	BCG	1762:1764	arg1	cells					1787:1791	BCG challenged-BC cancer cells	1762:1791	BCG challenged-BC cancer cells	1762:1791	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	0	23	theme	sialyltransferase	93:109	arg1	ST3GAL1					111:117	sialyltransferase ST3GAL1	93:117	sialyltransferase ST3GAL1	93:117	Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.
29454317	9	24	theme	increased	1527:1535	arg1	sensitivity					1537:1547	increased sensitivity	1527:1547	increased sensitivity to oxidative damage	1527:1567	Several genes preserving genomic stability were down-regulated in HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage.
29454317	9	24	theme	increased	1527:1535	arg1	consequence					1504:1514	a consequence	1502:1514	a consequence	1502:1514	Several genes preserving genomic stability were down-regulated in HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage.
29454317	5	25	theme	gene	915:918	arg1	expression					920:929	Whole gene expression	909:929	Whole gene expression	909:929	Whole gene expression was studied by microarray technology, cytokine secretion was measured by multiplex immune-beads assay.
29454317	7	26	theme	HT1376T	1285:1291	arg1	cells					1293:1297	HT1376T cells	1285:1297	HT1376T cells	1285:1297	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	10	27	theme	higher	1634:1639	arg1	susceptibility					1641:1654	higher susceptibility	1634:1654	higher susceptibility to BCG modulation	1634:1672	After BCG challenge, the transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation than that of HT1376T cells.
29454317	0	28	theme	Oxidative	0:8	arg1	damage					10:15	Oxidative damage	0:15	Oxidative damage	0:15	Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.
29454317	1	29	theme	BACKGROUND	120:129	arg1	Treatment					131:139	BACKGROUND Treatment	120:139	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG)	120:175	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	29	theme	BACKGROUND	120:129	arg1	immunotherapy					207:219	the gold standard adjuvant immunotherapy	180:219	the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC)	180:265	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	7	30	theme	IL-10	1266:1270	arg1	secretion					1231:1239	a stronger macrophage secretion	1209:1239	a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10	1209:1270	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	3	31	theme	cell	634:637	arg1	line					639:642	The human bladder cancer (BC) cell line HT1376	604:649	The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen	604:683	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	8	32	theme	T/sT	1365:1368	arg1	replacement					1370:1380	T/sT replacement	1365:1380	T/sT replacement	1365:1380	Transcriptomic analysis revealed that ST3GAL1 overexpression and T/sT replacement modulated hundreds of genes.
29454317	7	33	theme	TNFα	1257:1260	arg1	secretion					1231:1239	a stronger macrophage secretion	1209:1239	a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10	1209:1270	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	7	34	dep	RESULTS	1144:1150	arg1	induced					1201:1207	induced	1201:1207	induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells	1201:1297	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	3	35	theme	BC	630:631	arg1	line					639:642	The human bladder cancer (BC) cell line HT1376	604:649	The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen	604:683	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	2	36	theme	tumor-associated	336:351	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	36	theme	tumor-associated	336:351	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	36	theme	tumor-associated	336:351	arg1	counterpart					463:473	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	1	37	theme	patients	306:313	arg1	third					293:297	third	293:297	third	293:297	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	5	38	theme	cytokine	969:976	arg1	secretion					978:986	cytokine secretion	969:986	cytokine secretion	969:986	Whole gene expression was studied by microarray technology, cytokine secretion was measured by multiplex immune-beads assay.
29454317	7	39	theme	IL-1β	1250:1254	arg1	secretion					1231:1239	a stronger macrophage secretion	1209:1239	a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10	1209:1270	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	10	40	theme	HT1376T	1687:1693	arg1	cells					1695:1699	HT1376T cells	1687:1699	HT1376T cells	1687:1699	After BCG challenge, the transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation than that of HT1376T cells.
29454317	1	41	theme	bladder	244:250	arg1	NMIBC					260:264	NMIBC	260:264	NMIBC	260:264	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	41	theme	bladder	244:250	arg1	cancer					252:257	non-muscle invasive bladder cancer	224:257	non-muscle invasive bladder cancer (NMIBC)	224:265	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	7	42	theme	IL-6	1244:1247	arg1	secretion					1231:1239	a stronger macrophage secretion	1209:1239	a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10	1209:1270	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	2	43	theme	Thomsen-Friedenreich	410:429	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	43	theme	Thomsen-Friedenreich	410:429	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	7	44	theme	stronger	1211:1218	arg1	secretion					1231:1239	a stronger macrophage secretion	1209:1239	a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10	1209:1270	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	2	45	from	roles	561:565	arg1	response					574:581	BCG response	570:581	BCG response	570:581	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	3	46	theme	T	675:675	arg1	antigen					677:683	the T antigen	671:683	the T antigen	671:683	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	6	47	theme	cells	1137:1141	arg1	secretome					1106:1114	the secretome	1102:1114	the secretome of BCG-challenged BC cells	1102:1141	Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.
29454317	2	48	link	O-linked	353:360	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	48	link	O-linked	353:360	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	48	link	O-linked	353:360	arg1	counterpart					463:473	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	9	49	theme	Several	1411:1417	arg1	genes					1419:1423	Several genes	1411:1423	Several genes preserving genomic stability	1411:1452	Several genes preserving genomic stability were down-regulated in HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage.
29454317	6	50	theme	BCG-challenged	1119:1132	arg1	cells					1137:1141	BCG-challenged BC cells	1119:1141	BCG-challenged BC cells	1119:1141	Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.
29454317	1	51	theme	standard	189:196	arg1	Treatment					131:139	BACKGROUND Treatment	120:139	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG)	120:175	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	51	theme	standard	189:196	arg1	immunotherapy					207:219	the gold standard adjuvant immunotherapy	180:219	the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC)	180:265	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	11	52	theme	macrophage	1811:1820	arg1	response					1822:1829	a stronger macrophage response	1800:1829	a stronger macrophage response	1800:1829	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	10	53	theme	cells	1621:1625	arg1	transcriptome					1595:1607	the transcriptome	1591:1607	the transcriptome of HT1376sT cells	1591:1625	After BCG challenge, the transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation than that of HT1376T cells.
29454317	3	54	theme	ST3GAL1	723:729	arg1	cDNA					731:734	the ST3GAL1 cDNA	719:734	the ST3GAL1 cDNA	719:734	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	5	55	theme	immune-beads	1014:1025	arg1	assay					1027:1031	multiplex immune-beads assay	1004:1031	multiplex immune-beads assay	1004:1031	Whole gene expression was studied by microarray technology, cytokine secretion was measured by multiplex immune-beads assay.
29454317	9	56	theme	genomic	1436:1442	arg1	stability					1444:1452	genomic stability	1436:1452	genomic stability	1436:1452	Several genes preserving genomic stability were down-regulated in HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage.
29454317	1	57	theme	non-muscle	224:233	arg1	NMIBC					260:264	NMIBC	260:264	NMIBC	260:264	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	57	theme	non-muscle	224:233	arg1	cancer					252:257	non-muscle invasive bladder cancer	224:257	non-muscle invasive bladder cancer (NMIBC)	224:265	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	2	58	theme	sialyltransferase	528:544	arg1	ST3GAL1					546:552	sialyltransferase ST3GAL1	528:552	sialyltransferase ST3GAL1	528:552	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	9	59	theme	HT1376sT	1477:1484	arg1	cells					1486:1490	HT1376sT cells	1477:1490	HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage	1477:1567	Several genes preserving genomic stability were down-regulated in HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage.
29454317	2	60	theme	BCG	570:572	arg1	response					574:581	BCG response	570:581	BCG response	570:581	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	3	61	theme	bladder	614:620	arg1	line					639:642	The human bladder cancer (BC) cell line HT1376	604:649	The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen	604:683	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	7	62	from	cells	1195:1199	arg1	secretome					1156:1164	The secretome	1152:1164	The secretome from BCG-challenged HT1376sT cells	1152:1199	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	3	63	theme	cell	774:777	arg1	HT1376sT					785:792	HT1376sT	785:792	HT1376sT	785:792	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	3	63	theme	cell	774:777	arg1	lines					779:783	the cell lines HT1376sT and HT1376T	770:804	the cell lines HT1376sT and HT1376T	770:804	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	3	63	theme	cell	774:777	arg1	HT1376T					798:804	HT1376T	798:804	HT1376T	798:804	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	0	64	theme	cancer	69:74	arg1	cells					76:80	bladder cancer cells	61:80	bladder cancer cells expressing sialyltransferase ST3GAL1	61:117	Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.
29454317	0	65	from	response	21:28	arg1	cells					76:80	bladder cancer cells	61:80	bladder cancer cells expressing sialyltransferase ST3GAL1	61:117	Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.
29454317	11	66	theme	T/sT	1742:1745	arg1	replacement					1747:1757	T/sT replacement	1742:1757	T/sT replacement	1742:1757	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	7	67	theme	BCG-challenged	1171:1184	arg1	cells					1195:1199	BCG-challenged HT1376sT cells	1171:1199	BCG-challenged HT1376sT cells	1171:1199	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	2	68	dep	counterpart	463:473	arg1	sT					508:509	sT	508:509	sT	508:509	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	11	69	from	expression	1727:1736	arg1	cells					1787:1791	BCG challenged-BC cancer cells	1762:1791	BCG challenged-BC cancer cells	1762:1791	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	0	70	from	damage	10:15	arg1	cells					76:80	bladder cancer cells	61:80	bladder cancer cells expressing sialyltransferase ST3GAL1	61:117	Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.
29454317	6	71	theme	blood	1065:1069	arg1	monocytes					1071:1079	blood monocytes	1065:1079	blood monocytes	1065:1079	Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.
29454317	5	72	theme	Whole	909:913	arg1	expression					920:929	Whole gene expression	909:929	Whole gene expression	909:929	Whole gene expression was studied by microarray technology, cytokine secretion was measured by multiplex immune-beads assay.
29454317	3	73	theme	T	856:856	arg1	antigens					858:865	T antigens	856:865	the T antigens	852:865	METHODS The human bladder cancer (BC) cell line HT1376 strongly expressing the T antigen, was retrovirally transduced with the ST3GAL1 cDNA or with an empty vector, yielding the cell lines HT1376sT and HT1376T, that express, respectively, either the sT or the T antigens.
29454317	11	74	theme	challenged-BC	1766:1778	arg1	cells					1787:1791	BCG challenged-BC cancer cells	1762:1791	BCG challenged-BC cancer cells	1762:1791	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	8	75	theme	Transcriptomic	1300:1313	arg1	analysis					1315:1322	Transcriptomic analysis	1300:1322	Transcriptomic analysis	1300:1322	Transcriptomic analysis revealed that ST3GAL1 overexpression and T/sT replacement modulated hundreds of genes.
29454317	2	76	theme	Galβ1,3GalNAc	395:407	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	76	theme	Galβ1,3GalNAc	395:407	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	1	77	with	Treatment	131:139	arg1	BCG					172:174	BCG	172:174	BCG	172:174	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	77	with	Treatment	131:139	arg1	Calmette-Guérin					155:169	Bacillus Calmette-Guérin	146:169	Bacillus Calmette-Guérin (BCG)	146:175	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	9	78	theme	oxidative	1552:1560	arg1	damage					1562:1567	oxidative damage	1552:1567	oxidative damage	1552:1567	Several genes preserving genomic stability were down-regulated in HT1376sT cells which, as a consequence, displayed increased sensitivity to oxidative damage.
29454317	11	79	theme	High	1714:1717	arg1	expression					1727:1736	CONCLUSIONS High ST3GAL1 expression	1702:1736	CONCLUSIONS High ST3GAL1 expression	1702:1736	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	2	80	theme	disaccharide	381:392	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	80	theme	disaccharide	381:392	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	6	81	attach	derived	1052:1058	arg1	monocytes					1071:1079	blood monocytes	1065:1079	blood monocytes	1065:1079	Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.
29454317	6	81	attach	derived	1052:1058	arg2	macrophages					1040:1050	Human macrophages	1034:1050	Human macrophages derived from blood monocytes	1034:1079	Human macrophages derived from blood monocytes were challenged with the secretome of BCG-challenged BC cells.
29454317	8	82	theme	ST3GAL1	1338:1344	arg1	overexpression					1346:1359	ST3GAL1 overexpression	1338:1359	ST3GAL1 overexpression	1338:1359	Transcriptomic analysis revealed that ST3GAL1 overexpression and T/sT replacement modulated hundreds of genes.
29454317	2	83	theme	T	432:432	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	83	theme	T	432:432	arg1	antigen					435:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen	377:441	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	0	84	theme	Bacillus	33:40	arg1	Calmette-Guérin					42:56	Bacillus Calmette-Guérin	33:56	Bacillus Calmette-Guérin	33:56	Oxidative damage and response to Bacillus Calmette-Guérin in bladder cancer cells expressing sialyltransferase ST3GAL1.
29454317	5	85	theme	microarray	946:955	arg1	technology					957:966	microarray technology	946:966	microarray technology	946:966	Whole gene expression was studied by microarray technology, cytokine secretion was measured by multiplex immune-beads assay.
29454317	10	86	theme	BCG	1659:1661	arg1	modulation					1663:1672	BCG modulation	1659:1672	BCG modulation	1659:1672	After BCG challenge, the transcriptome of HT1376sT cells showed higher susceptibility to BCG modulation than that of HT1376T cells.
29454317	2	87	gly	sialylated	452:461	arg1	counterpart					463:473	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	87	gly	sialylated	452:461	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	87	gly	sialylated	452:461	arg1	Siaα2,3Galβ1,3GalNAc					476:495	Siaα2,3Galβ1,3GalNAc	476:495	Siaα2,3Galβ1,3GalNAc	476:495	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	1	88	theme	adjuvant	198:205	arg1	Treatment					131:139	BACKGROUND Treatment	120:139	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG)	120:175	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	88	theme	adjuvant	198:205	arg1	immunotherapy					207:219	the gold standard adjuvant immunotherapy	180:219	the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC)	180:265	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	2	89	theme	sialylated	452:461	arg1	counterpart					463:473	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT)	448:510	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	89	theme	sialylated	452:461	arg1	carbohydrates					362:374	two tumor-associated O-linked carbohydrates	332:374	two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown	332:593	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	2	89	theme	sialylated	452:461	arg1	Siaα2,3Galβ1,3GalNAc					476:495	Siaα2,3Galβ1,3GalNAc	476:495	Siaα2,3Galβ1,3GalNAc	476:495	NMIBC expresses two tumor-associated O-linked carbohydrates: the disaccharide (Galβ1,3GalNAc) Thomsen-Friedenreich (T) antigen, and its sialylated counterpart (Siaα2,3Galβ1,3GalNAc) sialyl-T (sT), synthesized by sialyltransferase ST3GAL1, whose roles in BCG response are unknown.
29454317	11	90	theme	ST3GAL1	1719:1725	arg1	expression					1727:1736	CONCLUSIONS High ST3GAL1 expression	1702:1736	CONCLUSIONS High ST3GAL1 expression	1702:1736	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	11	91	theme	genomic	1869:1875	arg1	instability					1877:1887	genomic instability	1869:1887	genomic instability	1869:1887	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	11	92	theme	CONCLUSIONS	1702:1712	arg1	expression					1727:1736	CONCLUSIONS High ST3GAL1 expression	1702:1736	CONCLUSIONS High ST3GAL1 expression	1702:1736	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	1	93	theme	cancer	252:257	arg1	Treatment					131:139	BACKGROUND Treatment	120:139	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG)	120:175	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	1	93	theme	cancer	252:257	arg1	immunotherapy					207:219	the gold standard adjuvant immunotherapy	180:219	the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC)	180:265	BACKGROUND Treatment with Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant immunotherapy of non-muscle invasive bladder cancer (NMIBC), although it fails in one third of the patients.
29454317	7	94	theme	macrophage	1220:1229	arg1	secretion					1231:1239	a stronger macrophage secretion	1209:1239	a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10	1209:1270	RESULTS The secretome from BCG-challenged HT1376sT cells induced a stronger macrophage secretion of IL-6, IL-1β, TNFα and IL-10 than that of HT1376T cells.
29454317	11	95	theme	BC	1923:1924	arg1	biology					1926:1932	BC biology	1923:1932	BC biology	1923:1932	CONCLUSIONS High ST3GAL1 expression and T/sT replacement in BCG challenged-BC cancer cells induce a stronger macrophage response and alter the gene expression towards genomic instability, indicating a potential impact on BC biology and patient's response to BCG.
29454317	8	96	theme	genes	1404:1408	arg1	hundreds					1392:1399	hundreds	1392:1399	hundreds of genes	1392:1408	Transcriptomic analysis revealed that ST3GAL1 overexpression and T/sT replacement modulated hundreds of genes.
29237830	17	0	theme	receptor	2626:2633	arg1	activation					2635:2644	virus-induced receptor activation	2612:2644	virus-induced receptor activation	2612:2644	Productive entry requires virus-induced receptor activation, involves macropinocytosis, and critically depends on LAMP-1.
29237830	10	1	theme	heparan	1523:1529	arg1	sulfate					1531:1537	heparan sulfate	1523:1537	heparan sulfate	1523:1537	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	6	2	theme	LASV	817:820	arg1	candidates					831:840	LASV receptor candidates	817:840	LASV receptor candidates in primary human cells	817:863	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	2	3	theme	receptor	333:340	arg1	dystroglycan					342:353	the highly conserved extracellular matrix receptor dystroglycan	291:353	the highly conserved extracellular matrix receptor dystroglycan (DG)	291:358	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	3	theme	receptor	333:340	arg1	receptor					270:277	The major cellular receptor	251:277	The major cellular receptor for LASV	251:286	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	3	theme	receptor	333:340	arg1	DG					356:357	DG	356:357	DG	356:357	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	1	4	theme	tissue	235:240	arg1	tropism					242:248	broad tissue tropism	229:248	broad tissue tropism	229:248	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	14	5	from	role	2347:2350	arg1	entry					2360:2364	LASV entry	2355:2364	LASV entry	2355:2364	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	7	6	theme	biosafety	1129:1137	arg1	glycoprotein					1085:1096	LASV glycoprotein	1080:1096	LASV glycoprotein (rLCMV-LASV GP)	1080:1112	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	6	theme	biosafety	1129:1137	arg1	model					1154:1158	a validated biosafety level 2 (BSL2) model	1117:1158	a validated biosafety level 2 (BSL2) model	1117:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	2	7	theme	cellular	261:268	arg1	dystroglycan					342:353	the highly conserved extracellular matrix receptor dystroglycan	291:353	the highly conserved extracellular matrix receptor dystroglycan (DG)	291:358	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	7	theme	cellular	261:268	arg1	receptor					270:277	The major cellular receptor	251:277	The major cellular receptor for LASV	251:286	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	12	8	theme	public	1975:1980	arg1	problem					1989:1995	a serious public health problem	1965:1995	a serious public health problem in Africa	1965:2005	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	6	9	theme	Axl	891:893	arg1	coexpression					875:886	coexpression	875:886	coexpression of Axl with differentially glycosylated DG	875:929	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	8	10	theme	LASV	1232:1235	arg1	entry					1237:1241	LASV entry	1232:1241	LASV entry	1232:1241	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	13	11	theme	virus	2092:2096	arg1	binding					2098:2104	virus binding	2092:2104	virus binding	2092:2104	Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism.
29237830	4	12	gly	glycosylation	520:532	arg1	DG					537:538	DG	537:538	DG	537:538	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	9	13	theme	receptor	1409:1416	arg1	activation					1418:1427	receptor activation	1409:1427	receptor activation	1409:1427	We further show that Axl-dependent LASV entry requires receptor activation and involves a pathway resembling macropinocytosis.
29237830	8	14	theme	previous	1183:1190	arg1	work					1192:1195	previous work	1183:1195	previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses	1183:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	15	15	from	role	2409:2412	arg1	entry					2429:2433	LASV entry	2424:2433	LASV entry	2424:2433	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	12	16	from	problem	1989:1995	arg1	Africa					2000:2005	Africa	2000:2005	Africa	2000:2005	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	18	17	theme	endothelial	2711:2721	arg1	cells					2723:2727	endothelial cells	2711:2727	endothelial cells that express low levels of glycosylated DG	2711:2770	In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry.
29237830	16	18	theme	functional	2521:2530	arg1	DG					2532:2533	functional DG	2521:2533	functional DG	2521:2533	We found that in the absence of functional DG, Axl can mediate LASV entry via apoptotic mimicry.
29237830	14	19	theme	LASV	2355:2358	arg1	entry					2360:2364	LASV entry	2355:2364	LASV entry	2355:2364	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	10	20	theme	endosomal	1574:1582	arg1	LAMP-1					1592:1597	the late endosomal protein LAMP-1	1565:1597	the late endosomal protein LAMP-1 as an intracellular entry factor	1565:1630	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	18	21	gly	glycosylated	2756:2767	arg1	DG					2769:2770	glycosylated DG	2756:2770	glycosylated DG	2756:2770	In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry.
29237830	7	22	theme	rLCMV-LASV	1099:1108	arg1	glycoprotein					1085:1096	LASV glycoprotein	1080:1096	LASV glycoprotein (rLCMV-LASV GP)	1080:1112	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	22	theme	rLCMV-LASV	1099:1108	arg1	GP					1110:1111	rLCMV-LASV GP	1099:1111	rLCMV-LASV GP	1099:1111	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	5	23	from	role	753:756	arg1	entry					766:770	LASV entry	761:770	LASV entry	761:770	However, their role in LASV entry is not entirely understood.
29237830	12	24	theme	pathogenic	1913:1922	arg1	LASV					1948:1951	LASV	1948:1951	LASV	1948:1951	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	12	24	theme	pathogenic	1913:1922	arg1	virus					1941:1945	The highly pathogenic arenavirus Lassa virus	1902:1945	The highly pathogenic arenavirus Lassa virus (LASV)	1902:1952	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	4	25	theme	receptor	717:724	arg1	receptors					648:656	The broadly expressed phosphatidylserine (PS) receptors	602:656	The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3	602:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	25	theme	receptor	717:724	arg1	candidates					726:735	alternative LASV receptor candidates	700:735	alternative LASV receptor candidates	700:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	8	26	theme	functional	1261:1270	arg1	DG					1272:1273	functional DG	1261:1273	functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses	1261:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	10	27	theme	entry	1619:1623	arg1	factor					1625:1630	an intracellular entry factor	1602:1630	an intracellular entry factor	1602:1630	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	9	28	theme	Axl-dependent	1375:1387	arg1	entry					1394:1398	Axl-dependent LASV entry	1375:1398	Axl-dependent LASV entry	1375:1398	We further show that Axl-dependent LASV entry requires receptor activation and involves a pathway resembling macropinocytosis.
29237830	15	29	theme	LASV	2424:2427	arg1	entry					2429:2433	LASV entry	2424:2433	LASV entry	2424:2433	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	1	30	theme	extensive	187:195	arg1	dissemination					203:215	extensive viral dissemination	187:215	extensive viral dissemination	187:215	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	12	31	theme	Lassa	1935:1939	arg1	LASV					1948:1951	LASV	1948:1951	LASV	1948:1951	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	12	31	theme	Lassa	1935:1939	arg1	virus					1941:1945	The highly pathogenic arenavirus Lassa virus	1902:1945	The highly pathogenic arenavirus Lassa virus (LASV)	1902:1952	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	17	32	theme	Productive	2586:2595	arg1	entry					2597:2601	Productive entry	2586:2601	Productive entry	2586:2601	Productive entry requires virus-induced receptor activation, involves macropinocytosis, and critically depends on LAMP-1.
29237830	15	33	theme	Axl	2417:2419	arg1	role					2409:2412	the exact role	2399:2412	the exact role of Axl in LASV entry	2399:2433	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	15	33	theme	Axl	2417:2419	arg1	function					2440:2447	a function	2438:2447	a function of DG's posttranslational modification	2438:2486	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	1	34	theme	Fatal	105:109	arg1	infection					111:119	Fatal infection	105:119	Fatal infection with the highly pathogenic Lassa virus (LASV)	105:165	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	16	35	theme	LASV	2552:2555	arg1	entry					2557:2561	LASV entry	2552:2561	LASV entry	2552:2561	We found that in the absence of functional DG, Axl can mediate LASV entry via apoptotic mimicry.
29237830	8	36	theme	apoptotic	1282:1290	arg1	"					1299:1299	"apoptotic mimicry"	1281:1299	"apoptotic mimicry" in a way similar to that of other enveloped viruses	1281:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	14	37	theme	alternative	2302:2312	arg1	Axl					2268:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	14	37	theme	alternative	2302:2312	arg1	candidate					2328:2336	an alternative LASV receptor candidate	2299:2336	an alternative LASV receptor candidate	2299:2336	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	7	38	theme	choriomeningitis	1046:1061	arg1	virus					1063:1067	recombinant lymphocytic choriomeningitis virus	1022:1067	recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model	1022:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	39	theme	arenavirus	988:997	arg1	infection					999:1007	productive arenavirus infection	977:1007	productive arenavirus infection	977:1007	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	13	40	theme	LASV	2031:2034	arg1	receptor					2036:2043	the principal LASV receptor	2017:2043	the principal LASV receptor	2017:2043	Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism.
29237830	13	40	theme	LASV	2031:2034	arg1	dystroglycan					2046:2057	dystroglycan	2046:2057	dystroglycan (DG)	2046:2062	Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism.
29237830	3	41	with	modification	427:438	arg1	matriglycan					481:491	the unusual O-linked polysaccharide matriglycan	445:491	the unusual O-linked polysaccharide matriglycan	445:491	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	7	42	gly	glycoprotein	1085:1096	arg1	glycoprotein					1085:1096	LASV glycoprotein	1080:1096	LASV glycoprotein (rLCMV-LASV GP)	1080:1112	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	42	gly	glycoprotein	1085:1096	arg1	GP					1110:1111	rLCMV-LASV GP	1099:1111	rLCMV-LASV GP	1099:1111	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	42	gly	glycoprotein	1085:1096	arg1	model					1154:1158	a validated biosafety level 2 (BSL2) model	1117:1158	a validated biosafety level 2 (BSL2) model	1117:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	11	43	theme	productive	1756:1765	arg1	entry					1767:1771	productive entry	1756:1771	productive entry	1756:1771	In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry.
29237830	19	44	theme	antiviral	2915:2923	arg1	therapy					2925:2931	antiviral therapy	2915:2931	antiviral therapy	2915:2931	In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.
29237830	15	45	theme	posttranslational	2457:2473	arg1	modification					2475:2486	DG's posttranslational modification	2452:2486	DG's posttranslational modification	2452:2486	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	1	46	theme	Lassa	148:152	arg1	LASV					161:164	LASV	161:164	LASV	161:164	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	1	46	theme	Lassa	148:152	arg1	virus					154:158	the highly pathogenic Lassa virus	126:158	the highly pathogenic Lassa virus (LASV)	126:165	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	8	47	theme	similar	1310:1316	arg1	way					1306:1308	a way	1304:1308	a way similar to that of other enveloped viruses	1304:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	6	48	gly	glycosylated	915:926	arg1	DG					928:929	differentially glycosylated DG	900:929	differentially glycosylated DG	900:929	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	0	49	theme	Functional	63:72	arg1	Glycosylation					74:86	the Functional Glycosylation	59:86	the Functional Glycosylation of Dystroglycan	59:102	Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan.
29237830	14	50	theme	phosphatidylserine	2240:2257	arg1	Axl					2268:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	14	50	theme	phosphatidylserine	2240:2257	arg1	candidate					2328:2336	an alternative LASV receptor candidate	2299:2336	an alternative LASV receptor candidate	2299:2336	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	3	51	theme	posttranslational	409:425	arg1	modification					427:438	DG's tissue-specific posttranslational modification	388:438	DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan	388:491	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	7	52	theme	LASV	941:944	arg1	use					955:957	LASV receptor use	941:957	LASV receptor use	941:957	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	8	53	theme	other	1329:1333	arg1	viruses					1345:1351	other enveloped viruses	1329:1351	other enveloped viruses	1329:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	8	54	from	"	1299:1299	arg1	way					1306:1308	a way	1304:1308	a way similar to that of other enveloped viruses	1304:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	0	55	gly	Glycosylation	74:86	arg1	Dystroglycan					91:102	Dystroglycan	91:102	Dystroglycan	91:102	Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan.
29237830	10	56	theme	LASV	1494:1497	arg1	entry					1499:1503	Axl-mediated LASV entry	1481:1503	Axl-mediated LASV entry	1481:1503	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	3	57	theme	unusual	449:455	arg1	matriglycan					481:491	the unusual O-linked polysaccharide matriglycan	445:491	the unusual O-linked polysaccharide matriglycan	445:491	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	4	58	theme	viral	571:575	arg1	tropism					577:583	viral tropism	571:583	viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates	571:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	0	59	theme	Entry	17:21	arg1	Factor					23:28	Entry Factor	17:28	Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan	17:102	Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan.
29237830	4	60	dep	receptors	648:656	arg1	receptors					648:656	The broadly expressed phosphatidylserine (PS) receptors	602:656	The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3	602:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	60	dep	receptors	648:656	arg1	Tyro3					666:670	Tyro3	666:670	Tyro3	666:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	60	dep	receptors	648:656	arg1	Axl					658:660	Axl	658:660	Axl	658:660	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	3	61	theme	LASV	372:375	arg1	Binding					361:367	Binding	361:367	Binding of LASV	361:375	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	4	62	theme	DG	537:538	arg1	glycosylation					520:532	functional glycosylation	509:532	functional glycosylation of DG	509:538	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	11	63	theme	DG	1690:1691	arg1	levels					1669:1674	low levels	1665:1674	low levels of functional DG	1665:1691	In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry.
29237830	2	64	theme	matrix	326:331	arg1	dystroglycan					342:353	the highly conserved extracellular matrix receptor dystroglycan	291:353	the highly conserved extracellular matrix receptor dystroglycan (DG)	291:358	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	64	theme	matrix	326:331	arg1	receptor					270:277	The major cellular receptor	251:277	The major cellular receptor for LASV	251:286	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	64	theme	matrix	326:331	arg1	DG					356:357	DG	356:357	DG	356:357	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	7	65	theme	BSL2	1148:1151	arg1	glycoprotein					1085:1096	LASV glycoprotein	1080:1096	LASV glycoprotein (rLCMV-LASV GP)	1080:1112	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	65	theme	BSL2	1148:1151	arg1	model					1154:1158	a validated biosafety level 2 (BSL2) model	1117:1158	a validated biosafety level 2 (BSL2) model	1117:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	18	66	theme	LASV	2800:2803	arg1	entry					2805:2809	LASV entry	2800:2809	LASV entry	2800:2809	In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry.
29237830	6	67	theme	primary	845:851	arg1	cells					859:863	primary human cells	845:863	primary human cells	845:863	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	4	68	located	observed	585:592	arg1	vivo					597:600	vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates	597:735	vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates	597:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	68	located	observed	585:592	arg2	tropism					577:583	viral tropism	571:583	viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates	571:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	2	69	theme	conserved	302:310	arg1	dystroglycan					342:353	the highly conserved extracellular matrix receptor dystroglycan	291:353	the highly conserved extracellular matrix receptor dystroglycan (DG)	291:358	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	69	theme	conserved	302:310	arg1	receptor					270:277	The major cellular receptor	251:277	The major cellular receptor for LASV	251:286	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	69	theme	conserved	302:310	arg1	DG					356:357	DG	356:357	DG	356:357	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	1	70	theme	viral	197:201	arg1	dissemination					203:215	extensive viral dissemination	187:215	extensive viral dissemination	187:215	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	12	71	theme	health	1982:1987	arg1	problem					1989:1995	a serious public health problem	1965:1995	a serious public health problem in Africa	1965:2005	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	6	72	with	coexpression	875:886	arg1	DG					928:929	differentially glycosylated DG	900:929	differentially glycosylated DG	900:929	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	4	73	theme	phosphatidylserine	624:641	arg1	receptors					648:656	The broadly expressed phosphatidylserine (PS) receptors	602:656	The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3	602:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	73	theme	phosphatidylserine	624:641	arg1	candidates					726:735	alternative LASV receptor candidates	700:735	alternative LASV receptor candidates	700:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	73	theme	phosphatidylserine	624:641	arg1	Axl					658:660	Axl	658:660	Axl	658:660	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	73	theme	phosphatidylserine	624:641	arg1	Tyro3					666:670	Tyro3	666:670	Tyro3	666:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	7	74	theme	level	1139:1143	arg1	glycoprotein					1085:1096	LASV glycoprotein	1080:1096	LASV glycoprotein (rLCMV-LASV GP)	1080:1112	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	74	theme	level	1139:1143	arg1	model					1154:1158	a validated biosafety level 2 (BSL2) model	1117:1158	a validated biosafety level 2 (BSL2) model	1117:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	18	75	theme	glycosylated	2756:2767	arg1	DG					2769:2770	glycosylated DG	2756:2770	glycosylated DG	2756:2770	In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry.
29237830	1	76	theme	broad	229:233	arg1	tropism					242:248	broad tissue tropism	229:248	broad tissue tropism	229:248	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	6	77	theme	glycosylated	915:926	arg1	DG					928:929	differentially glycosylated DG	900:929	differentially glycosylated DG	900:929	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	10	78	theme	late	1569:1572	arg1	LAMP-1					1592:1597	the late endosomal protein LAMP-1	1565:1597	the late endosomal protein LAMP-1 as an intracellular entry factor	1565:1630	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	7	79	theme	validated	1119:1127	arg1	glycoprotein					1085:1096	LASV glycoprotein	1080:1096	LASV glycoprotein (rLCMV-LASV GP)	1080:1112	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	79	theme	validated	1119:1127	arg1	model					1154:1158	a validated biosafety level 2 (BSL2) model	1117:1158	a validated biosafety level 2 (BSL2) model	1117:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	15	80	theme	exact	2403:2407	arg1	role					2409:2412	the exact role	2399:2412	the exact role of Axl in LASV entry	2399:2433	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	15	80	theme	exact	2403:2407	arg1	function					2440:2447	a function	2438:2447	a function of DG's posttranslational modification	2438:2486	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	9	81	theme	LASV	1389:1392	arg1	entry					1394:1398	Axl-dependent LASV entry	1375:1398	Axl-dependent LASV entry	1375:1398	We further show that Axl-dependent LASV entry requires receptor activation and involves a pathway resembling macropinocytosis.
29237830	3	82	link	O-linked	457:464	arg1	matriglycan					481:491	the unusual O-linked polysaccharide matriglycan	445:491	the unusual O-linked polysaccharide matriglycan	445:491	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	4	83	theme	LASV	712:715	arg1	receptors					648:656	The broadly expressed phosphatidylserine (PS) receptors	602:656	The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3	602:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	83	theme	LASV	712:715	arg1	candidates					726:735	alternative LASV receptor candidates	700:735	alternative LASV receptor candidates	700:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	16	84	theme	apoptotic	2567:2575	arg1	mimicry					2577:2583	apoptotic mimicry	2567:2583	apoptotic mimicry	2567:2583	We found that in the absence of functional DG, Axl can mediate LASV entry via apoptotic mimicry.
29237830	2	85	theme	major	255:259	arg1	dystroglycan					342:353	the highly conserved extracellular matrix receptor dystroglycan	291:353	the highly conserved extracellular matrix receptor dystroglycan (DG)	291:358	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	85	theme	major	255:259	arg1	receptor					270:277	The major cellular receptor	251:277	The major cellular receptor for LASV	251:286	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	12	86	theme	serious	1967:1973	arg1	problem					1989:1995	a serious public health problem	1965:1995	a serious public health problem in Africa	1965:2005	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	12	87	dep	targeting	1856:1864	arg1	represents					1954:1963	represents	1954:1963	represents a serious public health problem in Africa	1954:2005	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	11	88	theme	low	1665:1667	arg1	levels					1669:1674	low levels	1665:1674	low levels of functional DG	1665:1691	In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry.
29237830	16	89	theme	DG	2532:2533	arg1	absence					2510:2516	the absence	2506:2516	the absence of functional DG	2506:2533	We found that in the absence of functional DG, Axl can mediate LASV entry via apoptotic mimicry.
29237830	10	90	theme	protein	1584:1590	arg1	LAMP-1					1592:1597	the late endosomal protein LAMP-1	1565:1597	the late endosomal protein LAMP-1 as an intracellular entry factor	1565:1630	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	14	91	theme	receptor	2319:2326	arg1	Axl					2268:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	14	91	theme	receptor	2319:2326	arg1	candidate					2328:2336	an alternative LASV receptor candidate	2299:2336	an alternative LASV receptor candidate	2299:2336	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	6	92	from	candidates	831:840	arg1	cells					859:863	primary human cells	845:863	primary human cells	845:863	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	7	93	theme	LASV	1080:1083	arg1	glycoprotein					1085:1096	LASV glycoprotein	1080:1096	LASV glycoprotein (rLCMV-LASV GP)	1080:1112	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	93	theme	LASV	1080:1083	arg1	GP					1110:1111	rLCMV-LASV GP	1099:1111	rLCMV-LASV GP	1099:1111	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	7	93	theme	LASV	1080:1083	arg1	model					1154:1158	a validated biosafety level 2 (BSL2) model	1117:1158	a validated biosafety level 2 (BSL2) model	1117:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	4	94	dep	vivo	597:600	arg1	identified					686:695	identified	686:695	were recently identified as alternative LASV receptor candidates	672:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	10	95	theme	intracellular	1605:1617	arg1	factor					1625:1630	an intracellular entry factor	1602:1630	an intracellular entry factor	1602:1630	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	7	96	theme	recombinant	1022:1032	arg1	virus					1063:1067	recombinant lymphocytic choriomeningitis virus	1022:1067	recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model	1022:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	12	97	theme	arenavirus	1924:1933	arg1	LASV					1948:1951	LASV	1948:1951	LASV	1948:1951	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	12	97	theme	arenavirus	1924:1933	arg1	virus					1941:1945	The highly pathogenic arenavirus Lassa virus	1902:1945	The highly pathogenic arenavirus Lassa virus (LASV)	1902:1952	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	8	98	theme	DG	1272:1273	arg1	absence					1250:1256	the absence	1246:1256	the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses	1246:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	14	99	theme	LASV	2314:2317	arg1	Axl					2268:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	14	99	theme	LASV	2314:2317	arg1	candidate					2328:2336	an alternative LASV receptor candidate	2299:2336	an alternative LASV receptor candidate	2299:2336	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	7	100	theme	lymphocytic	1034:1044	arg1	virus					1063:1067	recombinant lymphocytic choriomeningitis virus	1022:1067	recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model	1022:1158	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	17	101	theme	virus-induced	2612:2624	arg1	activation					2635:2644	virus-induced receptor activation	2612:2644	virus-induced receptor activation	2612:2644	Productive entry requires virus-induced receptor activation, involves macropinocytosis, and critically depends on LAMP-1.
29237830	3	102	theme	polysaccharide	466:479	arg1	matriglycan					481:491	the unusual O-linked polysaccharide matriglycan	445:491	the unusual O-linked polysaccharide matriglycan	445:491	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	5	103	theme	LASV	761:764	arg1	entry					766:770	LASV entry	761:770	LASV entry	761:770	However, their role in LASV entry is not entirely understood.
29237830	7	104	theme	infection	999:1007	arg1	context					966:972	the context	962:972	the context of productive arenavirus infection	962:1007	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	13	105	theme	tissue	2202:2207	arg1	tropism					2209:2215	tissue tropism	2202:2215	tissue tropism	2202:2215	Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism.
29237830	4	106	theme	functional	509:518	arg1	glycosylation					520:532	functional glycosylation	509:532	functional glycosylation of DG	509:538	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	8	107	theme	mimicry	1292:1298	arg1	"					1299:1299	"apoptotic mimicry"	1281:1299	"apoptotic mimicry" in a way similar to that of other enveloped viruses	1281:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	19	108	from	roles	2842:2846	arg1	entry					2863:2867	LASV entry	2858:2867	LASV entry	2858:2867	In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.
29237830	12	109	theme	antiviral	1873:1881	arg1	therapy.IMPORTANCE					1883:1900	antiviral therapy.IMPORTANCE	1873:1900	antiviral therapy.IMPORTANCE	1873:1900	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	7	110	theme	productive	977:986	arg1	infection					999:1007	productive arenavirus infection	977:1007	productive arenavirus infection	977:1007	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	1	111	theme	pathogenic	137:146	arg1	LASV					161:164	LASV	161:164	LASV	161:164	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	1	111	theme	pathogenic	137:146	arg1	virus					154:158	the highly pathogenic Lassa virus	126:158	the highly pathogenic Lassa virus (LASV)	126:165	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	12	112	from	Axl	1866:1868	arg1	therapy.IMPORTANCE					1883:1900	antiviral therapy.IMPORTANCE	1873:1900	antiviral therapy.IMPORTANCE	1873:1900	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	4	113	theme	alternative	700:710	arg1	receptors					648:656	The broadly expressed phosphatidylserine (PS) receptors	602:656	The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3	602:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	113	theme	alternative	700:710	arg1	candidates					726:735	alternative LASV receptor candidates	700:735	alternative LASV receptor candidates	700:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	15	114	theme	modification	2475:2486	arg1	function					2440:2447	a function	2438:2447	a function of DG's posttranslational modification	2438:2486	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	15	114	theme	modification	2475:2486	arg1	role					2409:2412	the exact role	2399:2412	the exact role of Axl in LASV entry	2399:2433	Here, we investigate the exact role of Axl in LASV entry as a function of DG's posttranslational modification.
29237830	19	115	theme	LASV	2858:2861	arg1	entry					2863:2867	LASV entry	2858:2867	LASV entry	2858:2867	In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.
29237830	14	116	theme	receptor	2259:2266	arg1	Axl					2268:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	14	116	theme	receptor	2259:2266	arg1	candidate					2328:2336	an alternative LASV receptor candidate	2299:2336	an alternative LASV receptor candidate	2299:2336	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	0	117	theme	Dystroglycan	91:102	arg1	Glycosylation					74:86	the Functional Glycosylation	59:86	the Functional Glycosylation of Dystroglycan	59:102	Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan.
29237830	1	118	with	infection	111:119	arg1	LASV					161:164	LASV	161:164	LASV	161:164	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	1	118	with	infection	111:119	arg1	virus					154:158	the highly pathogenic Lassa virus	126:158	the highly pathogenic Lassa virus (LASV)	126:165	Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism.
29237830	14	119	theme	expressed	2230:2238	arg1	Axl					2268:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl	2218:2270	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	14	119	theme	expressed	2230:2238	arg1	candidate					2328:2336	an alternative LASV receptor candidate	2299:2336	an alternative LASV receptor candidate	2299:2336	The broadly expressed phosphatidylserine receptor Axl was recently identified as an alternative LASV receptor candidate, but its role in LASV entry is unclear.
29237830	13	120	theme	principal	2021:2029	arg1	receptor					2036:2043	the principal LASV receptor	2017:2043	the principal LASV receptor	2017:2043	Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism.
29237830	13	120	theme	principal	2021:2029	arg1	dystroglycan					2046:2057	dystroglycan	2046:2057	dystroglycan (DG)	2046:2062	Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism.
29237830	7	121	theme	receptor	946:953	arg1	use					955:957	LASV receptor use	941:957	LASV receptor use	941:957	To study LASV receptor use in the context of productive arenavirus infection, we employed recombinant lymphocytic choriomeningitis virus expressing LASV glycoprotein (rLCMV-LASV GP) as a validated biosafety level 2 (BSL2) model.
29237830	3	122	theme	tissue-specific	393:407	arg1	modification					427:438	DG's tissue-specific posttranslational modification	388:438	DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan	388:491	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	19	123	from	Axl	2908:2910	arg1	therapy					2925:2931	antiviral therapy	2915:2931	antiviral therapy	2915:2931	In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.
29237830	10	124	theme	Axl-mediated	1481:1492	arg1	entry					1499:1503	Axl-mediated LASV entry	1481:1503	Axl-mediated LASV entry	1481:1503	Axl-mediated LASV entry is facilitated by heparan sulfate and critically depends on the late endosomal protein LAMP-1 as an intracellular entry factor.
29237830	8	125	theme	enveloped	1335:1343	arg1	viruses					1345:1351	other enveloped viruses	1329:1351	other enveloped viruses	1329:1351	We confirm and extend previous work showing that Axl can contribute to LASV entry in the absence of functional DG using "apoptotic mimicry" in a way similar to that of other enveloped viruses.
29237830	3	126	theme	O-linked	457:464	arg1	matriglycan					481:491	the unusual O-linked polysaccharide matriglycan	445:491	the unusual O-linked polysaccharide matriglycan	445:491	Binding of LASV depends on DG's tissue-specific posttranslational modification with the unusual O-linked polysaccharide matriglycan.
29237830	19	127	theme	Axl	2851:2853	arg1	roles					2842:2846	the roles	2838:2846	the roles of Axl in LASV entry	2838:2867	In sum, our study defines the roles of Axl in LASV entry and provides a rationale for targeting Axl in antiviral therapy.
29237830	11	128	theme	functional	1679:1688	arg1	DG					1690:1691	functional DG	1679:1691	functional DG	1679:1691	In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry.
29237830	0	129	theme	Lassa	34:38	arg1	Virus					40:44	Lassa Virus	34:44	Lassa Virus Depending on the Functional Glycosylation of Dystroglycan	34:102	Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan.
29237830	12	130	theme	Axl	1810:1812	arg1	role					1802:1805	the role	1798:1805	the role of Axl in LASV entry	1798:1826	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	6	131	theme	human	853:857	arg1	cells					859:863	primary human cells	845:863	primary human cells	845:863	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	12	132	from	role	1802:1805	arg1	entry					1822:1826	LASV entry	1817:1826	LASV entry	1817:1826	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	18	133	theme	low	2742:2744	arg1	levels					2746:2751	low levels	2742:2751	low levels of glycosylated DG	2742:2770	In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry.
29237830	2	134	theme	extracellular	312:324	arg1	dystroglycan					342:353	the highly conserved extracellular matrix receptor dystroglycan	291:353	the highly conserved extracellular matrix receptor dystroglycan (DG)	291:358	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	134	theme	extracellular	312:324	arg1	receptor					270:277	The major cellular receptor	251:277	The major cellular receptor for LASV	251:286	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	2	134	theme	extracellular	312:324	arg1	DG					356:357	DG	356:357	DG	356:357	The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG).
29237830	12	135	theme	LASV	1817:1820	arg1	entry					1822:1826	LASV entry	1817:1826	LASV entry	1817:1826	In sum, we characterize the role of Axl in LASV entry and provide a rationale for targeting Axl in antiviral therapy.IMPORTANCE The highly pathogenic arenavirus Lassa virus (LASV) represents a serious public health problem in Africa.
29237830	4	136	theme	expressed	614:622	arg1	receptors					648:656	The broadly expressed phosphatidylserine (PS) receptors	602:656	The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3	602:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	136	theme	expressed	614:622	arg1	candidates					726:735	alternative LASV receptor candidates	700:735	alternative LASV receptor candidates	700:735	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	136	theme	expressed	614:622	arg1	Axl					658:660	Axl	658:660	Axl	658:660	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	4	136	theme	expressed	614:622	arg1	Tyro3					666:670	Tyro3	666:670	Tyro3	666:670	Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates.
29237830	6	137	theme	receptor	822:829	arg1	candidates					831:840	LASV receptor candidates	817:840	LASV receptor candidates in primary human cells	817:863	Here, we examine LASV receptor candidates in primary human cells and found coexpression of Axl with differentially glycosylated DG.
29237830	11	138	theme	endothelial	1636:1646	arg1	cells					1648:1652	endothelial cells	1636:1652	endothelial cells expressing low levels of functional DG	1636:1691	In endothelial cells expressing low levels of functional DG, both receptors are engaged by the virus and can contribute to productive entry.
29237830	18	139	theme	DG	2769:2770	arg1	levels					2746:2751	low levels	2742:2751	low levels of glycosylated DG	2742:2770	In endothelial cells that express low levels of glycosylated DG, both receptors can promote LASV entry.
29237830	13	140	theme	posttranslational	2133:2149	arg1	modification					2151:2162	DG's posttranslational modification	2128:2162	DG's posttranslational modification	2128:2162	Although the principal LASV receptor, dystroglycan (DG), is ubiquitously expressed, virus binding critically depends on DG's posttranslational modification, which does not always correlate with tissue tropism.
28344780	8	0	theme	O-linked	1015:1022	arg1	glycosylation					1024:1036	O-linked glycosylation	1015:1036	O-linked glycosylation	1015:1036	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	4	1	theme	clinical	577:584	arg1	evaluation					586:595	full clinical evaluation	572:595	full clinical evaluation of the proband	572:610	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	6	2	with	chromatography	798:811	arg1	detection					838:846	pulsed amperometric detection	818:846	pulsed amperometric detection	818:846	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	5	3	theme	staining	652:659	arg1	Analyses					613:620	Analyses	613:620	Analyses of cilia formation and lectin staining	613:659	Analyses of cilia formation and lectin staining were performed by immunofluorescence.
28344780	3	4	contain	carried	327:333	arg2	mutation					344:351	the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del)	335:392	the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del)	335:392	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	3	4	contain	carried	327:333	arg1	He					324:325	He	324:325	He	324:325	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	11	5	theme	total	1297:1301	arg1	levels					1312:1317	total cellular levels	1297:1317	total cellular levels of CMP-sialic acid	1297:1336	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	2	6	theme	syndrome	297:304	arg1	type					306:309	Joubert syndrome type 10	289:312	Joubert syndrome type 10 (JBTS10)	289:321	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	2	6	theme	syndrome	297:304	arg1	JBTS10					315:320	JBTS10	315:320	JBTS10	315:320	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	7	7	theme	t	912:912	arg1	tests					914:918	exact t tests	906:918	exact t tests	906:918	Statistical analyses utilized the Student's and Fisher's exact t tests.
28344780	5	8	theme	cilia	625:629	arg1	formation					631:639	cilia formation	625:639	cilia formation	625:639	Analyses of cilia formation and lectin staining were performed by immunofluorescence.
28344780	13	9	theme	WT	1509:1510	arg1	OFD1					1512:1515	WT OFD1	1509:1515	WT OFD1	1509:1515	CONCLUSIONS The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1 suggests that both contribute to the pathogenesis of JBTS10.
28344780	6	10	theme	amperometric	825:836	arg1	detection					838:846	pulsed amperometric detection	818:846	pulsed amperometric detection	818:846	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	2	11	dep	evaluation	239:248	arg1	the					235:237	the	235:237	the	235:237	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	11	12	theme	cellular	1303:1310	arg1	levels					1312:1317	total cellular levels	1297:1317	total cellular levels of CMP-sialic acid	1297:1336	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	13	13	theme	glycosylation	1472:1484	arg1	rescue					1445:1450	The rescue	1441:1450	The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1	1441:1515	CONCLUSIONS The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1 suggests that both contribute to the pathogenesis of JBTS10.
28344780	9	14	theme	unrelated	1081:1089	arg1	males					1091:1095	two unrelated males	1077:1095	two unrelated males with OFD1 mutations	1077:1115	These findings replicated in two unrelated males with OFD1 mutations.
28344780	1	15	dep	BACKGROUND	52:61	arg1	requires					101:108	requires	101:108	requires systematic agnostic screening of multiple homeostatic processes that may become deregulated	101:200	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	10	16	theme	Cultured	1118:1125	arg1	fibroblasts					1127:1137	Cultured fibroblasts	1118:1137	Cultured fibroblasts from affected individuals	1118:1163	Cultured fibroblasts from affected individuals had a defect in ciliogenesis.
28344780	2	17	theme	5-year-old	269:278	arg1	boy					280:282	a 5-year-old boy	267:282	a 5-year-old boy with Joubert syndrome type 10 (JBTS10)	267:321	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	1	18	theme	multiple	143:150	arg1	processes					164:172	multiple homeostatic processes	143:172	multiple homeostatic processes	143:172	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	13	19	theme	ciliogenesis	1455:1466	arg1	rescue					1445:1450	The rescue	1441:1450	The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1	1441:1515	CONCLUSIONS The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1 suggests that both contribute to the pathogenesis of JBTS10.
28344780	1	20	theme	processes	164:172	arg1	screening					130:138	systematic agnostic screening	110:138	systematic agnostic screening of multiple homeostatic processes that may become deregulated	110:200	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	4	21	theme	mass	489:492	arg1	spectrometry					494:505	MALDI-TOF mass spectrometry	479:505	MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes	479:565	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	3	22	theme	p.Gln886Lysfs	353:365	arg1	NM_003611.2					370:380	NM_003611.2	370:380	NM_003611.2: c.2656del	370:391	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	3	22	theme	p.Gln886Lysfs	353:365	arg1	*					366:366	p.Gln886Lysfs*2	353:367	the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del)	335:392	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	3	23	dep	NM_003611.2	370:380	arg1	c.2656del					383:391	c.2656del	383:391	NM_003611.2: c.2656del	370:391	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	8	24	link	O-linked	1015:1022	arg1	glycosylation					1024:1036	O-linked glycosylation	1015:1036	O-linked glycosylation	1015:1036	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	8	25	theme	RESULTS	921:927	arg1	analyses					937:944	RESULTS Glycome analyses	921:944	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts	921:986	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	3	26	theme	OFD1	339:342	arg1	mutation					344:351	the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del)	335:392	the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del)	335:392	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	4	27	theme	exome	461:465	arg1	sequencing					467:476	exome sequencing	461:476	exome sequencing	461:476	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	6	28	theme	nucleotide	723:732	arg1	levels					740:745	cellular nucleotide sugar levels	714:745	cellular nucleotide sugar levels	714:745	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	3	29	theme	Joubert	421:427	arg1	syndrome					429:436	Joubert syndrome	421:436	Joubert syndrome	421:436	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	9	30	with	males	1091:1095	arg1	mutations					1107:1115	OFD1 mutations	1102:1115	OFD1 mutations	1102:1115	These findings replicated in two unrelated males with OFD1 mutations.
28344780	11	31	theme	nuclear	1253:1259	arg1	signature					1273:1281	an abnormally elevated nuclear sialylation signature	1230:1281	an abnormally elevated nuclear sialylation signature	1230:1281	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	0	32	theme	Abnormal	0:7	arg1	glycosylation					9:21	Abnormal glycosylation	0:21	Abnormal glycosylation in Joubert syndrome type 10	0:49	Abnormal glycosylation in Joubert syndrome type 10.
28344780	1	33	theme	pathogenesis	88:99	arg1	discovery					67:75	The discovery	63:75	The discovery of disease pathogenesis	63:99	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	8	34	theme	plasma	949:954	arg1	analyses					937:944	RESULTS Glycome analyses	921:944	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts	921:986	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	4	35	theme	fibroblasts	546:556	arg1	glycomes					558:565	plasma and cultured dermal fibroblasts glycomes	519:565	plasma and cultured dermal fibroblasts glycomes	519:565	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	11	36	theme	CMP-sialic	1322:1331	arg1	acid					1333:1336	CMP-sialic acid	1322:1336	CMP-sialic acid	1322:1336	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	7	37	theme	Statistical	849:859	arg1	analyses					861:868	Statistical analyses	849:868	Statistical analyses	849:868	Statistical analyses utilized the Student's and Fisher's exact t tests.
28344780	1	38	theme	systematic	110:119	arg1	screening					130:138	systematic agnostic screening	110:138	systematic agnostic screening of multiple homeostatic processes that may become deregulated	110:200	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	8	39	theme	cultured	960:967	arg1	fibroblasts					976:986	cultured dermal fibroblasts	960:986	cultured dermal fibroblasts	960:986	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	12	40	theme	glycosylation	1361:1373	arg1	anomaly					1375:1381	each glycosylation anomaly	1356:1381	each glycosylation anomaly	1356:1381	Ciliogenesis and each glycosylation anomaly were rescued by expression of wild-type OFD1.
28344780	0	41	theme	syndrome	34:41	arg1	type					43:46	Joubert syndrome type 10	26:49	Joubert syndrome type 10	26:49	Abnormal glycosylation in Joubert syndrome type 10.
28344780	10	42	from	defect	1171:1176	arg1	ciliogenesis					1181:1192	ciliogenesis	1181:1192	ciliogenesis	1181:1192	Cultured fibroblasts from affected individuals had a defect in ciliogenesis.
28344780	0	43	gly	glycosylation	9:21	arg1	type					43:46	Joubert syndrome type 10	26:49	Joubert syndrome type 10	26:49	Abnormal glycosylation in Joubert syndrome type 10.
28344780	8	44	theme	fibroblasts	976:986	arg1	analyses					937:944	RESULTS Glycome analyses	921:944	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts	921:986	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	4	45	theme	plasma	519:524	arg1	glycomes					558:565	plasma and cultured dermal fibroblasts glycomes	519:565	plasma and cultured dermal fibroblasts glycomes	519:565	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	7	46	used	utilized	870:877	arg2	analyses					861:868	Statistical analyses	849:868	Statistical analyses	849:868	Statistical analyses utilized the Student's and Fisher's exact t tests.
28344780	13	47	dep	CONCLUSIONS	1429:1439	arg1	suggests					1517:1524	suggests	1517:1524	suggests that both contribute to the pathogenesis of JBTS10	1517:1575	CONCLUSIONS The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1 suggests that both contribute to the pathogenesis of JBTS10.
28344780	8	48	theme	abnormal	999:1006	arg1	profiles					1038:1045	abnormal N- and O-linked glycosylation profiles	999:1045	abnormal N- and O-linked glycosylation profiles	999:1045	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	4	49	theme	cultured	530:537	arg1	fibroblasts					546:556	cultured dermal fibroblasts	530:556	cultured dermal fibroblasts	530:556	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	6	50	theme	high-performance	766:781	arg1	chromatography					798:811	high-performance anion-exchange chromatography	766:811	high-performance anion-exchange chromatography with pulsed amperometric detection	766:846	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	13	51	theme	JBTS10	1570:1575	arg1	pathogenesis					1554:1565	the pathogenesis	1550:1565	the pathogenesis of JBTS10	1550:1575	CONCLUSIONS The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1 suggests that both contribute to the pathogenesis of JBTS10.
28344780	8	52	theme	glycosylation	1024:1036	arg1	profiles					1038:1045	abnormal N- and O-linked glycosylation profiles	999:1045	abnormal N- and O-linked glycosylation profiles	999:1045	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	5	53	theme	lectin	645:650	arg1	staining					652:659	lectin staining	645:659	lectin staining	645:659	Analyses of cilia formation and lectin staining were performed by immunofluorescence.
28344780	6	54	theme	levels	740:745	arg1	Measurement					699:709	Measurement	699:709	Measurement of cellular nucleotide sugar levels	699:745	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	4	55	theme	full	572:575	arg1	evaluation					586:595	full clinical evaluation	572:595	full clinical evaluation of the proband	572:610	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	4	56	dep	METHODS	439:445	arg1	We					447:448	We	447:448	We	447:448	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	2	57	theme	Joubert	289:295	arg1	type					306:309	Joubert syndrome type 10	289:312	Joubert syndrome type 10 (JBTS10)	289:321	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	2	57	theme	Joubert	289:295	arg1	JBTS10					315:320	JBTS10	315:320	JBTS10	315:320	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	5	58	theme	formation	631:639	arg1	Analyses					613:620	Analyses	613:620	Analyses of cilia formation and lectin staining	613:659	Analyses of cilia formation and lectin staining were performed by immunofluorescence.
28344780	7	59	theme	exact	906:910	arg1	tests					914:918	exact t tests	906:918	exact t tests	906:918	Statistical analyses utilized the Student's and Fisher's exact t tests.
28344780	13	60	theme	OFD1	1512:1515	arg1	reintroduction					1491:1504	reintroduction	1491:1504	reintroduction of WT OFD1	1491:1515	CONCLUSIONS The rescue of ciliogenesis and glycosylation upon reintroduction of WT OFD1 suggests that both contribute to the pathogenesis of JBTS10.
28344780	6	61	theme	pulsed	818:823	arg1	detection					838:846	pulsed amperometric detection	818:846	pulsed amperometric detection	818:846	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	1	62	theme	agnostic	121:128	arg1	screening					130:138	systematic agnostic screening	110:138	systematic agnostic screening of multiple homeostatic processes that may become deregulated	110:200	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	2	63	with	boy	280:282	arg1	type					306:309	Joubert syndrome type 10	289:312	Joubert syndrome type 10 (JBTS10)	289:321	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	2	63	with	boy	280:282	arg1	JBTS10					315:320	JBTS10	315:320	JBTS10	315:320	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	2	64	theme	boy	280:282	arg1	diagnosis					254:262	diagnosis	254:262	diagnosis	254:262	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	2	64	theme	boy	280:282	arg1	evaluation					239:248	evaluation	239:248	evaluation	239:248	We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10).
28344780	12	65	theme	OFD1	1423:1426	arg1	expression					1399:1408	expression	1399:1408	expression of wild-type OFD1	1399:1426	Ciliogenesis and each glycosylation anomaly were rescued by expression of wild-type OFD1.
28344780	9	66	theme	OFD1	1102:1105	arg1	mutations					1107:1115	OFD1 mutations	1102:1115	OFD1 mutations	1102:1115	These findings replicated in two unrelated males with OFD1 mutations.
28344780	1	67	theme	homeostatic	152:162	arg1	processes					164:172	multiple homeostatic processes	143:172	multiple homeostatic processes	143:172	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	4	68	theme	spectrometry	494:505	arg1	analyses					507:514	MALDI-TOF mass spectrometry analyses	479:514	MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes	479:565	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	0	69	from	glycosylation	9:21	arg1	type					43:46	Joubert syndrome type 10	26:49	Joubert syndrome type 10	26:49	Abnormal glycosylation in Joubert syndrome type 10.
28344780	10	70	theme	affected	1144:1151	arg1	individuals					1153:1163	affected individuals	1144:1163	affected individuals	1144:1163	Cultured fibroblasts from affected individuals had a defect in ciliogenesis.
28344780	11	71	theme	sialylation	1261:1271	arg1	signature					1273:1281	an abnormally elevated nuclear sialylation signature	1230:1281	an abnormally elevated nuclear sialylation signature	1230:1281	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	6	72	theme	sugar	734:738	arg1	levels					740:745	cellular nucleotide sugar levels	714:745	cellular nucleotide sugar levels	714:745	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	11	73	theme	elevated	1244:1251	arg1	signature					1273:1281	an abnormally elevated nuclear sialylation signature	1230:1281	an abnormally elevated nuclear sialylation signature	1230:1281	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	4	74	theme	MALDI-TOF	479:487	arg1	spectrometry					494:505	MALDI-TOF mass spectrometry	479:505	MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes	479:565	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	6	75	theme	cellular	714:721	arg1	levels					740:745	cellular nucleotide sugar levels	714:745	cellular nucleotide sugar levels	714:745	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	3	76	theme	syndrome	429:436	arg1	features					409:416	features	409:416	features of Joubert syndrome	409:436	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	10	77	from	individuals	1153:1163	arg1	fibroblasts					1127:1137	Cultured fibroblasts	1118:1137	Cultured fibroblasts from affected individuals	1118:1163	Cultured fibroblasts from affected individuals had a defect in ciliogenesis.
28344780	1	78	theme	disease	80:86	arg1	pathogenesis					88:99	disease pathogenesis	80:99	disease pathogenesis	80:99	BACKGROUND The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated.
28344780	8	79	theme	Glycome	929:935	arg1	analyses					937:944	RESULTS Glycome analyses	921:944	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts	921:986	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	12	80	theme	wild-type	1413:1421	arg1	OFD1					1423:1426	wild-type OFD1	1413:1426	wild-type OFD1	1413:1426	Ciliogenesis and each glycosylation anomaly were rescued by expression of wild-type OFD1.
28344780	4	81	theme	glycomes	558:565	arg1	evaluation					586:595	full clinical evaluation	572:595	full clinical evaluation of the proband	572:610	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	4	81	theme	glycomes	558:565	arg1	analyses					507:514	MALDI-TOF mass spectrometry analyses	479:514	MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes	479:565	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	4	81	theme	glycomes	558:565	arg1	sequencing					467:476	exome sequencing	461:476	exome sequencing	461:476	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	0	82	theme	Joubert	26:32	arg1	type					43:46	Joubert syndrome type 10	26:49	Joubert syndrome type 10	26:49	Abnormal glycosylation in Joubert syndrome type 10.
28344780	11	83	theme	acid	1333:1336	arg1	levels					1312:1317	total cellular levels	1297:1317	total cellular levels of CMP-sialic acid	1297:1336	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	8	84	theme	dermal	969:974	arg1	fibroblasts					976:986	cultured dermal fibroblasts	960:986	cultured dermal fibroblasts	960:986	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	4	85	theme	dermal	539:544	arg1	fibroblasts					546:556	cultured dermal fibroblasts	530:556	cultured dermal fibroblasts	530:556	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	3	86	dep	mutation	344:351	arg1	NM_003611.2					370:380	NM_003611.2	370:380	NM_003611.2: c.2656del	370:391	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	3	86	dep	mutation	344:351	arg1	*					366:366	p.Gln886Lysfs*2	353:367	the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del)	335:392	He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome.
28344780	6	87	theme	anion-exchange	783:796	arg1	chromatography					798:811	high-performance anion-exchange chromatography	766:811	high-performance anion-exchange chromatography with pulsed amperometric detection	766:846	Measurement of cellular nucleotide sugar levels was performed with high-performance anion-exchange chromatography with pulsed amperometric detection.
28344780	4	88	theme	proband	604:610	arg1	evaluation					586:595	full clinical evaluation	572:595	full clinical evaluation of the proband	572:610	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	4	88	theme	proband	604:610	arg1	analyses					507:514	MALDI-TOF mass spectrometry analyses	479:514	MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes	479:565	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	4	88	theme	proband	604:610	arg1	sequencing					467:476	exome sequencing	461:476	exome sequencing	461:476	METHODS We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband.
28344780	7	89	dep	Student	883:889	arg1	tests					914:918	exact t tests	906:918	exact t tests	906:918	Statistical analyses utilized the Student's and Fisher's exact t tests.
28344780	10	90	contain	had	1165:1167	arg1	fibroblasts					1127:1137	Cultured fibroblasts	1118:1137	Cultured fibroblasts from affected individuals	1118:1163	Cultured fibroblasts from affected individuals had a defect in ciliogenesis.
28344780	10	90	contain	had	1165:1167	arg2	defect					1171:1176	a defect	1169:1176	a defect in ciliogenesis	1169:1192	Cultured fibroblasts from affected individuals had a defect in ciliogenesis.
28344780	8	91	theme	N-	1008:1009	arg1	profiles					1038:1045	abnormal N- and O-linked glycosylation profiles	999:1045	abnormal N- and O-linked glycosylation profiles	999:1045	RESULTS Glycome analyses of plasma and cultured dermal fibroblasts identified abnormal N- and O-linked glycosylation profiles.
28344780	11	92	contain	had	1226:1228	arg1	fibroblasts					1209:1219	The proband's fibroblasts	1195:1219	The proband's fibroblasts	1195:1219	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
28344780	11	92	contain	had	1226:1228	arg2	signature					1273:1281	an abnormally elevated nuclear sialylation signature	1230:1281	an abnormally elevated nuclear sialylation signature	1230:1281	The proband's fibroblasts also had an abnormally elevated nuclear sialylation signature and increased total cellular levels of CMP-sialic acid.
30653653	0	0	theme	glycosylation	94:106	arg1	disorders					81:89	congenital disorders	70:89	congenital disorders of glycosylation in Spain	70:115	Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
30653653	7	1	located	found	862:866	arg1	genes					874:878	16 genes	871:878	16 genes	871:878	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	1	located	found	862:866	arg2	variations					846:855	Pathogenic variations	835:855	Pathogenic variations	835:855	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	6	2	theme	transferrin	761:771	arg1	profile					781:787	their serum transferrin isoform profile	749:787	their serum transferrin isoform profile	749:787	Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II.
30653653	2	3	dep	render	304:309	arg1	challenging					351:361	challenging	351:361	challenging	351:361	They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging.
30653653	9	4	theme	genetic	1110:1116	arg1	analyses					1134:1141	genetic and biochemical analyses	1110:1141	genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders	1110:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	6	5	theme	serum	755:759	arg1	profile					781:787	their serum transferrin isoform profile	749:787	their serum transferrin isoform profile	749:787	Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II.
30653653	4	6	theme	non-PMM2	587:594	arg1	patients					600:607	25 non-PMM2 CDG patients	584:607	25 non-PMM2 CDG patients	584:607	The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients.
30653653	3	7	theme	PMM2	386:389	arg1	CDG					415:417	the most common CDG	399:417	the most common CDG	399:417	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	3	7	theme	PMM2	386:389	arg1	-CDG					391:394	Phosphomannomutase 2 (PMM2)-CDG	364:394	Phosphomannomutase 2 (PMM2)-CDG	364:394	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	1	8	gly	glycoprotein	181:192	arg1	glycoprotein					181:192	glycoprotein	181:192	glycoprotein	181:192	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	2	9	theme	CDG	342:344	arg1	diagnosis					315:323	the diagnosis	311:323	the diagnosis of the different CDG	311:344	They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging.
30653653	3	10	theme	Phosphomannomutase	364:381	arg1	CDG					415:417	the most common CDG	399:417	the most common CDG	399:417	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	3	10	theme	Phosphomannomutase	364:381	arg1	-CDG					391:394	Phosphomannomutase 2 (PMM2)-CDG	364:394	Phosphomannomutase 2 (PMM2)-CDG	364:394	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	9	11	theme	biochemical	1122:1132	arg1	analyses					1134:1141	genetic and biochemical analyses	1110:1141	genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders	1110:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	5	12	theme	common	619:624	arg1	hypotonia					649:657	hypotonia	649:657	hypotonia (80%)	649:663	The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%).
30653653	5	12	theme	common	619:624	arg1	symptoms					635:642	The most common clinical symptoms	610:642	The most common clinical symptoms	610:642	The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%).
30653653	2	13	theme	non-specific	282:293	arg1	symptoms					295:302	non-specific symptoms	282:302	non-specific symptoms	282:302	They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging.
30653653	3	14	theme	genetic	436:442	arg1	analysis					444:451	genetic analysis	436:451	genetic analysis	436:451	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	5	15	theme	clinical	626:633	arg1	hypotonia					649:657	hypotonia	649:657	hypotonia (80%)	649:663	The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%).
30653653	5	15	theme	clinical	626:633	arg1	symptoms					635:642	The most common clinical symptoms	610:642	The most common clinical symptoms	610:642	The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%).
30653653	2	16	theme	different	332:340	arg1	CDG					342:344	the different CDG	328:344	the different CDG	328:344	They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging.
30653653	1	17	theme	glycoprotein	181:192	arg1	synthesis					216:224	glycoprotein and glycolipid glycan synthesis	181:224	glycoprotein and glycolipid glycan synthesis	181:224	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	0	18	theme	Clinical	0:7	arg1	diagnosis					23:31	Clinical and molecular diagnosis	0:31	Clinical and molecular diagnosis of non-phosphomannomutase 2	0:59	Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
30653653	4	19	theme	clinical	548:555	arg1	spectrum					572:579	the clinical and mutational spectrum	544:579	the clinical and mutational spectrum of 25 non-PMM2 CDG patients	544:607	The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients.
30653653	9	20	theme	early	1151:1155	arg1	diagnosis					1157:1165	the early diagnosis	1147:1165	the early diagnosis of this heterogeneous group of disorders	1147:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	1	21	theme	glycolipid	198:207	arg1	synthesis					216:224	glycoprotein and glycolipid glycan synthesis	181:224	glycoprotein and glycolipid glycan synthesis	181:224	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	0	22	theme	molecular	13:21	arg1	diagnosis					23:31	Clinical and molecular diagnosis	0:31	Clinical and molecular diagnosis of non-phosphomannomutase 2	0:59	Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
30653653	4	23	theme	mutational	561:570	arg1	spectrum					572:579	the clinical and mutational spectrum	544:579	the clinical and mutational spectrum of 25 non-PMM2 CDG patients	544:607	The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients.
30653653	5	24	theme	psychomotor	675:685	arg1	disability					687:696	psychomotor disability	675:696	psychomotor disability	675:696	The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%).
30653653	1	25	theme	glycan	209:214	arg1	synthesis					216:224	glycoprotein and glycolipid glycan synthesis	181:224	glycoprotein and glycolipid glycan synthesis	181:224	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	0	26	theme	non-phosphomannomutase	36:57	arg1	diagnosis					23:31	Clinical and molecular diagnosis	0:31	Clinical and molecular diagnosis of non-phosphomannomutase 2	0:59	Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
30653653	8	27	theme	which	1043:1047	arg1	which					1043:1047	which	1043:1047	which	1043:1047	Overall, 27 variants were identified, 12 of which are novel.
30653653	8	27	theme	which	1043:1047	arg1	12					1037:1038	12	1037:1038	12	1037:1038	Overall, 27 variants were identified, 12 of which are novel.
30653653	4	28	theme	present	523:529	arg1	work					531:534	The present work	519:534	The present work	519:534	The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients.
30653653	8	29	dep	identified	1025:1034	arg1	novel					1053:1057	novel	1053:1057	novel	1053:1057	Overall, 27 variants were identified, 12 of which are novel.
30653653	0	30	from	disorders	81:89	arg1	Spain					111:115	Spain	111:115	Spain	111:115	Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
30653653	9	31	theme	heterogeneous	1175:1187	arg1	disorders					1198:1206	disorders	1198:1206	disorders	1198:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	9	31	theme	heterogeneous	1175:1187	arg1	group					1189:1193	this heterogeneous group	1170:1193	this heterogeneous group of disorders	1170:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	1	32	theme	congenital	122:131	arg1	defects					170:176	defects	170:176	defects in glycoprotein and glycolipid glycan synthesis and attachment	170:239	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	1	32	theme	congenital	122:131	arg1	disorders					133:141	The congenital disorders	118:141	The congenital disorders of glycosylation (CDG)	118:164	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	3	33	theme	common	408:413	arg1	CDG					415:417	the most common CDG	399:417	the most common CDG	399:417	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	3	33	theme	common	408:413	arg1	-CDG					391:394	Phosphomannomutase 2 (PMM2)-CDG	364:394	Phosphomannomutase 2 (PMM2)-CDG	364:394	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	9	34	theme	group	1189:1193	arg1	diagnosis					1157:1165	the early diagnosis	1147:1165	the early diagnosis of this heterogeneous group of disorders	1147:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	7	35	dep	ALG1	881:884	arg1	RFT1					965:968	RFT1	965:968	RFT1	965:968	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	B4GALT1					903:909	B4GALT1	903:909	B4GALT1	903:909	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	DOLK					927:930	DOLK	927:930	DOLK	927:930	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	SSR4					992:995	SSR4	992:995	SSR4	992:995	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	SLC35A2					971:977	SLC35A2	971:977	SLC35A2	971:977	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	DPAGT1					933:938	DPAGT1	933:938	DPAGT1	933:938	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	MPI					954:956	MPI	954:956	MPI	954:956	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	ALG6					887:890	ALG6	887:890	ALG6	887:890	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	CCDC115					912:918	CCDC115	912:918	CCDC115	912:918	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	PGM1					959:962	PGM1	959:962	PGM1	959:962	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	SRD5A3					980:985	SRD5A3	980:985	SRD5A3	980:985	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	COG7					921:924	COG7	921:924	COG7	921:924	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	DPM1					941:944	DPM1	941:944	DPM1	941:944	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	ATP6V0A2					893:900	ATP6V0A2	893:900	ATP6V0A2	893:900	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	7	35	dep	ALG1	881:884	arg1	GFPT1					947:951	GFPT1	947:951	GFPT1	947:951	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	4	36	theme	patients	600:607	arg1	spectrum					572:579	the clinical and mutational spectrum	544:579	the clinical and mutational spectrum of 25 non-PMM2 CDG patients	544:607	The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients.
30653653	1	37	theme	glycosylation	146:158	arg1	defects					170:176	defects	170:176	defects in glycoprotein and glycolipid glycan synthesis and attachment	170:239	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	1	37	theme	glycosylation	146:158	arg1	disorders					133:141	The congenital disorders	118:141	The congenital disorders of glycosylation (CDG)	118:164	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	4	38	theme	CDG	596:598	arg1	patients					600:607	25 non-PMM2 CDG patients	584:607	25 non-PMM2 CDG patients	584:607	The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients.
30653653	5	39	theme	craniofacial	708:719	arg1	dysmorphism					721:731	craniofacial dysmorphism	708:731	craniofacial dysmorphism (76%)	708:737	The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%).
30653653	5	39	theme	craniofacial	708:719	arg1	%					736:736	76%	734:736	76%	734:736	The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%).
30653653	6	40	theme	isoform	773:779	arg1	profile					781:787	their serum transferrin isoform profile	749:787	their serum transferrin isoform profile	749:787	Based on their serum transferrin isoform profile, 18 were classified as CDG-I and 7 as CDG-II.
30653653	3	41	from	advances	424:431	arg1	analysis					444:451	genetic analysis	436:451	genetic analysis	436:451	Phosphomannomutase 2 (PMM2)-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought.
30653653	7	42	theme	Pathogenic	835:844	arg1	variations					846:855	Pathogenic variations	835:855	Pathogenic variations	835:855	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30653653	0	43	theme	congenital	70:79	arg1	disorders					81:89	congenital disorders	70:89	congenital disorders of glycosylation in Spain	70:115	Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
30653653	2	44	theme	multiple	254:261	arg1	organ/systems					263:275	multiple organ/systems	254:275	multiple organ/systems	254:275	They affect multiple organ/systems, but non-specific symptoms render the diagnosis of the different CDG very challenging.
30653653	1	45	from	defects	170:176	arg1	attachment					230:239	attachment	230:239	attachment	230:239	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	1	45	from	defects	170:176	arg1	synthesis					216:224	glycoprotein and glycolipid glycan synthesis	181:224	glycoprotein and glycolipid glycan synthesis	181:224	The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment.
30653653	9	46	theme	disorders	1198:1206	arg1	disorders					1198:1206	disorders	1198:1206	disorders	1198:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	9	46	theme	disorders	1198:1206	arg1	group					1189:1193	this heterogeneous group	1170:1193	this heterogeneous group of disorders	1170:1206	The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
30653653	7	47	dep	found	862:866	arg1	ALG1					881:884	ALG1	881:884	ALG1	881:884	Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, and SSR4).
30217930	4	0	theme	cancer	808:813	arg1	lines					820:824	thyroid cancer cell lines	800:824	thyroid cancer cell lines	800:824	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	0	1	with	Cross-talk	68:77	arg1	Signaling					89:97	PTEN Signaling	84:97	PTEN Signaling	84:97	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	8	2	theme	protumorigenic	1707:1720	arg1	role					1722:1725	A novel pump-independent protumorigenic role	1682:1725	A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer	1682:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	8	2	theme	protumorigenic	1707:1720	arg1	ineffective					1823:1833	ineffective	1823:1833	ineffective	1823:1833	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	7	3	theme	glycosylation	1481:1493	arg1	step					1464:1467	the initial step	1452:1467	the initial step of N-linked glycosylation	1452:1493	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	3	4	theme	Thyroid	528:534	arg1	cancer					536:541	Thyroid cancer	528:541	Thyroid cancer	528:541	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	4	5	theme	PTEN	782:785	arg1	knockdown					787:795	PTEN knockdown	782:795	PTEN knockdown in thyroid cancer cell lines	782:824	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	6	6	theme	pathway	1162:1168	arg1	activation					1120:1129	activation	1120:1129	activation of the PI3K/AKT/mTOR signaling pathway	1120:1168	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	6	7	theme	tumorigenic	1251:1261	arg1	function					1263:1270	its nonpump tumorigenic function	1239:1270	its nonpump tumorigenic function	1239:1270	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	8	8	theme	NIS	1744:1746	arg1	challenges					1748:1757	nonmembranous NIS challenges	1730:1757	nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer	1730:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	1	9	theme	classical	139:147	arg1	pump					156:159	a classical iodide pump	137:159	a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers	137:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	9	theme	classical	139:147	arg1	symporter					118:126	The sodium iodide symporter	100:126	The sodium iodide symporter (NIS)	100:132	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	7	10	theme	initial	1456:1462	arg1	step					1464:1467	the initial step	1452:1467	the initial step of N-linked glycosylation	1452:1493	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	6	11	theme	PI3K/AKT/mTOR	1138:1150	arg1	pathway					1162:1168	the PI3K/AKT/mTOR signaling pathway	1134:1168	the PI3K/AKT/mTOR signaling pathway	1134:1168	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	3	12	theme	noncanonical	690:701	arg1	role					715:718	the noncanonical tumorigenic role	686:718	the noncanonical tumorigenic role of NIS in thyroid cancer cells	686:749	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	3	13	theme	NIS	723:725	arg1	role					715:718	the noncanonical tumorigenic role	686:718	the noncanonical tumorigenic role of NIS in thyroid cancer cells	686:749	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	3	14	theme	cancers	573:579	arg1	cancers					573:579	the major component cancers	553:579	the major component cancers	553:579	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	3	14	theme	cancers	573:579	arg1	one					546:548	one	546:548	one	546:548	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	3	14	theme	cancers	573:579	arg1	subset					603:608	a subset	601:608	a subset	601:608	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	4	15	theme	intracellular	837:849	arg1	protein					855:861	intracellular NIS protein	837:861	intracellular NIS protein	837:861	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	1	16	located	localized	171:179	arg1	membrane					204:211	the cell plasma membrane	188:211	the cell plasma membrane	188:211	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	16	located	localized	171:179	arg2	symporter					118:126	The sodium iodide symporter	100:126	The sodium iodide symporter (NIS)	100:132	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	16	located	localized	171:179	arg2	pump					156:159	a classical iodide pump	137:159	a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers	137:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	3	17	theme	major	557:561	arg1	cancers					573:579	the major component cancers	553:579	the major component cancers	553:579	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	8	18	theme	thyroid	1805:1811	arg1	cancer					1813:1818	thyroid cancer	1805:1818	thyroid cancer	1805:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	1	19	theme	sodium	104:109	arg1	NIS					129:131	NIS	129:131	NIS	129:131	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	19	theme	sodium	104:109	arg1	symporter					118:126	The sodium iodide symporter	100:126	The sodium iodide symporter (NIS)	100:132	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	19	theme	sodium	104:109	arg1	pump					156:159	a classical iodide pump	137:159	a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers	137:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	7	20	gly	glycosylation	1507:1519	arg1	NIS					1524:1526	NIS	1524:1526	NIS	1524:1526	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	4	21	theme	guanine	931:937	arg1	NIS-LARG					896:903	NIS-LARG	896:903	NIS-LARG (leukemia-associated RhoA guanine exchange factor)	896:954	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	4	21	theme	guanine	931:937	arg1	factor					948:953	leukemia-associated RhoA guanine exchange factor	906:953	leukemia-associated RhoA guanine exchange factor	906:953	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	3	22	theme	thyroid	730:736	arg1	cells					745:749	thyroid cancer cells	730:749	thyroid cancer cells	730:749	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	0	23	theme	Thyroid	49:55	arg1	Cancer					57:62	Thyroid Cancer	49:62	Thyroid Cancer	49:62	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	1	24	theme	mainstay	285:292	arg1	therapy					306:312	mainstay radioiodide therapy	285:312	mainstay radioiodide therapy	285:312	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	3	25	theme	Cowden	584:589	arg1	syndrome					591:598	Cowden syndrome	584:598	Cowden syndrome	584:598	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	0	26	from	Function	10:17	arg1	Cancer					57:62	Thyroid Cancer	49:62	Thyroid Cancer	49:62	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	3	27	from	role	715:718	arg1	cells					745:749	thyroid cancer cells	730:749	thyroid cancer cells	730:749	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	6	28	from	mislocalization	1185:1199	arg1	cytoplasm					1215:1223	the cytoplasm	1211:1223	the cytoplasm	1211:1223	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	3	29	theme	PTEN	766:769	arg1	signaling					771:779	PTEN signaling	766:779	PTEN signaling	766:779	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	1	30	theme	therapy	306:312	arg1	success					274:280	success	274:280	success of mainstay radioiodide therapy in thyroid cancers	274:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	31	theme	thyroid	317:323	arg1	cancers					325:331	thyroid cancers	317:331	thyroid cancers	317:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	4	32	with	interaction	879:889	arg1	NIS-LARG					896:903	NIS-LARG	896:903	NIS-LARG (leukemia-associated RhoA guanine exchange factor)	896:954	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	4	32	with	interaction	879:889	arg1	factor					948:953	leukemia-associated RhoA guanine exchange factor	906:953	leukemia-associated RhoA guanine exchange factor	906:953	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	4	33	theme	leukemia-associated	906:924	arg1	NIS-LARG					896:903	NIS-LARG	896:903	NIS-LARG (leukemia-associated RhoA guanine exchange factor)	896:954	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	4	33	theme	leukemia-associated	906:924	arg1	factor					948:953	leukemia-associated RhoA guanine exchange factor	906:953	leukemia-associated RhoA guanine exchange factor	906:953	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	0	34	from	Symporter	36:44	arg1	Cancer					57:62	Thyroid Cancer	49:62	Thyroid Cancer	49:62	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	8	35	dep	challenges	1748:1757	arg1	presumption					1763:1773	the presumption	1759:1773	nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer	1730:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	2	36	theme	nonmembranous	423:435	arg1	NIS					437:439	intracellular nonmembranous NIS	409:439	intracellular nonmembranous NIS	409:439	Although radioiodide uptake is generally reduced in thyroid cancer tissue, intracellular nonmembranous NIS has been reported to increase, suggesting that NIS serves a pump-independent function.
30217930	1	37	theme	NIS	237:239	arg1	expression					241:250	NIS expression	237:250	NIS expression	237:250	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	2	38	theme	cancer	394:399	arg1	tissue					401:406	thyroid cancer tissue	386:406	thyroid cancer tissue	386:406	Although radioiodide uptake is generally reduced in thyroid cancer tissue, intracellular nonmembranous NIS has been reported to increase, suggesting that NIS serves a pump-independent function.
30217930	3	39	dep	PTEN	654:657	arg1	explored					677:684	explored	677:684	explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling	677:779	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	7	40	theme	glycosylating	1419:1431	arg1	enzyme					1433:1438	a glycosylating enzyme	1417:1438	a glycosylating enzyme involved in the initial step of N-linked glycosylation	1417:1493	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	7	40	theme	glycosylating	1419:1431	arg1	DPAGT1					1409:1414	DPAGT1	1409:1414	DPAGT1	1409:1414	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	0	41	theme	Sodium	22:27	arg1	Symporter					36:44	Sodium Iodide Symporter	22:44	Sodium Iodide Symporter in Thyroid Cancer	22:62	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	0	42	theme	Symporter	36:44	arg1	Function					10:17	A Nonpump Function	0:17	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.	0:98	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	5	43	theme	NIS	997:999	arg1	levels					975:980	Increased protein levels	957:980	Increased protein levels of cytoplasmic NIS	957:999	Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype.
30217930	6	44	theme	glycosylation	1098:1110	arg1	Inhibition					1080:1089	Inhibition	1080:1089	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway	1080:1168	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	8	45	theme	protumorigenic	1583:1596	arg1	pump-independent					1565:1580	a pump-independent	1563:1580	a pump-independent	1563:1580	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	8	45	theme	protumorigenic	1583:1596	arg1	role					1598:1601	protumorigenic role	1583:1601	protumorigenic role for NIS in thyroid cancer	1583:1627	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	3	46	theme	germline	632:639	arg1	mutations					641:649	germline mutations	632:649	germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling	632:779	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	1	47	theme	cell	192:195	arg1	membrane					204:211	the cell plasma membrane	188:211	the cell plasma membrane	188:211	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	9	48	dep	Res	1883:1885	arg1	Cancer					1876:1881	Cancer	1876:1881	Cancer	1876:1881	Cancer Res; 78(21); 6121-33.
30217930	6	49	with	interaction	1283:1293	arg1	LARG					1300:1303	LARG	1300:1303	LARG	1300:1303	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	5	50	theme	protein	967:973	arg1	levels					975:980	Increased protein levels	957:980	Increased protein levels of cytoplasmic NIS	957:999	Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype.
30217930	1	51	from	success	274:280	arg1	cancers					325:331	thyroid cancers	317:331	thyroid cancers	317:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	52	theme	thyroid	216:222	arg1	cells					224:228	thyroid cells	216:228	thyroid cells	216:228	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	7	53	theme	N-linked	1472:1479	arg1	glycosylation					1481:1493	N-linked glycosylation	1472:1493	N-linked glycosylation	1472:1493	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	4	54	theme	thyroid	800:806	arg1	lines					820:824	thyroid cancer cell lines	800:824	thyroid cancer cell lines	800:824	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	10	55	theme	©2018	1905:1909	arg1	AACR					1911:1914	©2018 AACR	1905:1914	©2018 AACR.	1905:1915	©2018 AACR.
30217930	8	56	theme	pump-independent	1690:1705	arg1	role					1722:1725	A novel pump-independent protumorigenic role	1682:1725	A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer	1682:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	8	56	theme	pump-independent	1690:1705	arg1	ineffective					1823:1833	ineffective	1823:1833	ineffective	1823:1833	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	4	57	theme	cell	815:818	arg1	lines					820:824	thyroid cancer cell lines	800:824	thyroid cancer cell lines	800:824	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	8	58	from	role	1598:1601	arg1	cancer					1622:1627	thyroid cancer	1614:1627	thyroid cancer	1614:1627	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	7	59	gly	glycosylating	1419:1431	arg0	DPAGT1					1409:1414	DPAGT1	1409:1414	DPAGT1	1409:1414	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	7	59	gly	glycosylating	1419:1431	arg0	enzyme					1433:1438	a glycosylating enzyme	1417:1438	a glycosylating enzyme involved in the initial step of N-linked glycosylation	1417:1493	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	6	60	theme	signaling	1152:1160	arg1	pathway					1162:1168	the PI3K/AKT/mTOR signaling pathway	1134:1168	the PI3K/AKT/mTOR signaling pathway	1134:1168	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	6	61	theme	nonpump	1243:1249	arg1	function					1263:1270	its nonpump tumorigenic function	1239:1270	its nonpump tumorigenic function	1239:1270	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	8	62	with	cross-talk	1637:1646	arg1	signaling.Significance					1658:1679	PTEN signaling.Significance	1653:1679	PTEN signaling.Significance	1653:1679	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	8	63	theme	nonmembranous	1730:1742	arg1	challenges					1748:1757	nonmembranous NIS challenges	1730:1757	nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer	1730:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	1	64	theme	iodide	149:154	arg1	pump					156:159	a classical iodide pump	137:159	a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers	137:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	64	theme	iodide	149:154	arg1	symporter					118:126	The sodium iodide symporter	100:126	The sodium iodide symporter (NIS)	100:132	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	7	65	link	N-linked	1472:1479	arg1	glycosylation					1481:1493	N-linked glycosylation	1472:1493	N-linked glycosylation	1472:1493	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	3	66	theme	tumorigenic	703:713	arg1	role					715:718	the noncanonical tumorigenic role	686:718	the noncanonical tumorigenic role of NIS in thyroid cancer cells	686:749	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	8	67	theme	challenges	1748:1757	arg1	role					1722:1725	A novel pump-independent protumorigenic role	1682:1725	A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer	1682:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	8	67	theme	challenges	1748:1757	arg1	ineffective					1823:1833	ineffective	1823:1833	ineffective	1823:1833	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	3	68	from	mutations	641:649	arg1	PTEN					654:657	PTEN	654:657	PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling	654:779	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	3	69	theme	component	563:571	arg1	cancers					573:579	the major component cancers	553:579	the major component cancers	553:579	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	2	70	theme	pump-independent	501:516	arg1	function					518:525	a pump-independent function	499:525	a pump-independent function	499:525	Although radioiodide uptake is generally reduced in thyroid cancer tissue, intracellular nonmembranous NIS has been reported to increase, suggesting that NIS serves a pump-independent function.
30217930	0	71	from	Cancer	57:62	arg1	Function					10:17	A Nonpump Function	0:17	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.	0:98	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	1	72	from	membrane	204:211	arg1	cells					224:228	thyroid cells	216:228	thyroid cells	216:228	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	5	73	theme	promigration	1044:1055	arg1	phenotype					1069:1077	a promigration tumorigenic phenotype	1042:1077	a promigration tumorigenic phenotype	1042:1077	Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype.
30217930	8	74	theme	radioiodine	1780:1790	arg1	treatment					1792:1800	radioiodine treatment	1780:1800	radioiodine treatment of thyroid cancer	1780:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	7	75	theme	PI3K/AKT/mTOR	1372:1384	arg1	signaling					1386:1394	PI3K/AKT/mTOR signaling	1372:1394	PI3K/AKT/mTOR signaling	1372:1394	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	5	76	theme	RhoA	1010:1013	arg1	activation					1015:1024	RhoA activation	1010:1024	RhoA activation	1010:1024	Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype.
30217930	3	77	theme	syndrome	591:598	arg1	cancers					573:579	the major component cancers	553:579	the major component cancers	553:579	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	1	78	theme	iodide	111:116	arg1	NIS					129:131	NIS	129:131	NIS	129:131	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	78	theme	iodide	111:116	arg1	symporter					118:126	The sodium iodide symporter	100:126	The sodium iodide symporter (NIS)	100:132	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	1	78	theme	iodide	111:116	arg1	pump					156:159	a classical iodide pump	137:159	a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers	137:331	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	4	79	theme	NIS	851:853	arg1	protein					855:861	intracellular NIS protein	837:861	intracellular NIS protein	837:861	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	6	80	theme	NIS	1204:1206	arg1	mislocalization					1185:1199	mislocalization	1185:1199	mislocalization of NIS in the cytoplasm	1185:1223	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	8	81	theme	cancer	1813:1818	arg1	treatment					1792:1800	radioiodine treatment	1780:1800	radioiodine treatment of thyroid cancer	1780:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	4	82	theme	RhoA	926:929	arg1	NIS-LARG					896:903	NIS-LARG	896:903	NIS-LARG (leukemia-associated RhoA guanine exchange factor)	896:954	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	4	82	theme	RhoA	926:929	arg1	factor					948:953	leukemia-associated RhoA guanine exchange factor	906:953	leukemia-associated RhoA guanine exchange factor	906:953	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	3	83	theme	cancer	738:743	arg1	cells					745:749	thyroid cancer cells	730:749	thyroid cancer cells	730:749	Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling.
30217930	1	84	theme	radioiodide	294:304	arg1	therapy					306:312	mainstay radioiodide therapy	285:312	mainstay radioiodide therapy	285:312	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	5	85	theme	tumorigenic	1057:1067	arg1	phenotype					1069:1077	a promigration tumorigenic phenotype	1042:1077	a promigration tumorigenic phenotype	1042:1077	Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype.
30217930	4	86	theme	exchange	939:946	arg1	NIS-LARG					896:903	NIS-LARG	896:903	NIS-LARG (leukemia-associated RhoA guanine exchange factor)	896:954	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	4	86	theme	exchange	939:946	arg1	factor					948:953	leukemia-associated RhoA guanine exchange factor	906:953	leukemia-associated RhoA guanine exchange factor	906:953	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	0	87	theme	PTEN	84:87	arg1	Signaling					89:97	PTEN Signaling	84:97	PTEN Signaling	84:97	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	8	88	theme	transmembrane	1840:1852	arg1	NIS					1854:1856	transmembrane NIS	1840:1856	transmembrane NIS	1840:1856	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	4	89	from	knockdown	787:795	arg1	lines					820:824	thyroid cancer cell lines	800:824	thyroid cancer cell lines	800:824	PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor).
30217930	0	90	theme	Nonpump	2:8	arg1	Function					10:17	A Nonpump Function	0:17	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.	0:98	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	2	91	theme	intracellular	409:421	arg1	NIS					437:439	intracellular nonmembranous NIS	409:439	intracellular nonmembranous NIS	409:439	Although radioiodide uptake is generally reduced in thyroid cancer tissue, intracellular nonmembranous NIS has been reported to increase, suggesting that NIS serves a pump-independent function.
30217930	2	92	theme	radioiodide	343:353	arg1	uptake					355:360	radioiodide uptake	343:360	radioiodide uptake	343:360	Although radioiodide uptake is generally reduced in thyroid cancer tissue, intracellular nonmembranous NIS has been reported to increase, suggesting that NIS serves a pump-independent function.
30217930	2	93	theme	thyroid	386:392	arg1	tissue					401:406	thyroid cancer tissue	386:406	thyroid cancer tissue	386:406	Although radioiodide uptake is generally reduced in thyroid cancer tissue, intracellular nonmembranous NIS has been reported to increase, suggesting that NIS serves a pump-independent function.
30217930	0	94	theme	Iodide	29:34	arg1	Symporter					36:44	Sodium Iodide Symporter	22:44	Sodium Iodide Symporter in Thyroid Cancer	22:62	A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling.
30217930	5	95	theme	cytoplasmic	985:995	arg1	NIS					997:999	cytoplasmic NIS	985:999	cytoplasmic NIS	985:999	Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype.
30217930	8	96	theme	PTEN	1653:1656	arg1	signaling.Significance					1658:1679	PTEN signaling.Significance	1653:1679	PTEN signaling.Significance	1653:1679	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	7	97	theme	NIS	1524:1526	arg1	glycosylation					1507:1519	glycosylation	1507:1519	glycosylation of NIS	1507:1526	Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS.
30217930	6	98	theme	NIS	1094:1096	arg1	glycosylation					1098:1110	NIS glycosylation	1094:1110	NIS glycosylation	1094:1110	Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm.
30217930	1	99	theme	plasma	197:202	arg1	membrane					204:211	the cell plasma membrane	188:211	the cell plasma membrane	188:211	The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers.
30217930	5	100	theme	Increased	957:965	arg1	levels					975:980	Increased protein levels	957:980	Increased protein levels of cytoplasmic NIS	957:999	Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype.
30217930	8	101	theme	thyroid	1614:1620	arg1	cancer					1622:1627	thyroid cancer	1614:1627	thyroid cancer	1614:1627	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	8	102	theme	novel	1684:1688	arg1	role					1722:1725	A novel pump-independent protumorigenic role	1682:1725	A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer	1682:1818	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30217930	8	102	theme	novel	1684:1688	arg1	ineffective					1823:1833	ineffective	1823:1833	ineffective	1823:1833	In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed.
30210230	17	0	dep	Conclusions	2555:2565	arg1	provided					2680:2687	provided	2680:2687	provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease	2680:2775	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	3	1	theme	series	641:646	arg1	generation					599:608	generation	599:608	generation	599:608	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	1	theme	series	641:646	arg1	transmission					623:634	germline transmission	614:634	germline transmission	614:634	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	11	2	theme	Rho	1806:1808	arg1	essential					1824:1832	essential	1824:1832	essential	1824:1832	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	11	2	theme	Rho	1806:1808	arg1	expression					1810:1819	the Rho expression	1802:1819	the Rho expression	1802:1819	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	12	3	theme	consensus	1949:1957	arg1	sequence					1959:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15.
30210230	6	4	theme	cone-specific	1129:1141	arg1	antibodies					1143:1152	rod- and cone-specific antibodies	1120:1152	rod- and cone-specific antibodies	1120:1152	Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes.
30210230	14	5	theme	premature	2151:2159	arg1	codon					2166:2170	a premature stop codon	2149:2170	a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence	2149:2226	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	14	5	theme	premature	2151:2159	arg1	*					2177:2177	S347*	2173:2177	S347*	2173:2177	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	3	6	theme	short	689:693	arg1	CRISPR					716:721	CRISPR	716:721	CRISPR	716:721	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	6	theme	short	689:693	arg1	repeats					707:713	novel clustered regularly interspaced short palindromic repeats	651:713	novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations	651:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	6	7	theme	rod-	1120:1123	arg1	antibodies					1143:1152	rod- and cone-specific antibodies	1120:1152	rod- and cone-specific antibodies	1120:1152	Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes.
30210230	14	8	theme	rh1-1	2096:2100	arg1	region					2086:2091	the 3'-coding region	2072:2091	the 3'-coding region of rh1-1	2072:2100	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	17	9	theme	CRISPR/Cas9	2585:2595	arg1	efficiency					2571:2580	The efficiency	2567:2580	The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP,	2567:2678	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	6	10	theme	cellular	1192:1199	arg1	changes					1201:1207	histological and cellular changes	1175:1207	histological and cellular changes	1175:1207	Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes.
30210230	14	11	theme	phosphorylation	2285:2299	arg1	site					2301:2304	the putative phosphorylation site	2272:2304	the putative phosphorylation site at S339	2272:2312	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	1	12	theme	disorders	176:184	arg1	pigmentosa					133:142	Purpose Retinitis pigmentosa	115:142	Purpose Retinitis pigmentosa (RP)	115:147	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	1	12	theme	disorders	176:184	arg1	collection					154:163	a collection	152:163	a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness	152:278	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	12	13	theme	N-linked	1926:1933	arg1	sequence					1959:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15.
30210230	3	14	theme	repeats	707:713	arg1	series					641:646	a series	639:646	a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations	639:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	5	15	theme	length	1012:1017	arg1	polymorphism					1019:1030	restriction fragment length polymorphism	991:1030	restriction fragment length polymorphism (RFLP)	991:1037	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	5	15	theme	length	1012:1017	arg1	RFLP					1033:1036	RFLP	1033:1036	RFLP	1033:1036	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	11	16	with	labeling	1703:1710	arg1	antibody					1732:1739	a Rho-specific antibody	1717:1739	a Rho-specific antibody	1717:1739	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	4	17	theme	staged	844:849	arg1	embryos					861:867	One- or two-cell staged zebrafish embryos	827:867	Methods One- or two-cell staged zebrafish embryos	819:867	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	7	18	theme	alleles	1314:1320	arg1	series					1281:1286	a series	1279:1286	a series of dominant and recessive alleles	1279:1320	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	10	19	theme	shift	1560:1564	arg1	mutation					1566:1573	A frame shift mutation	1552:1573	A frame shift mutation leading to a premature stop codon (T17*)	1552:1614	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	3	20	theme	/Cas9-induced	723:735	arg1	insertion					737:745	/Cas9-induced insertion	723:745	/Cas9-induced insertion	723:745	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	18	21	theme	high	2840:2843	arg1	screens					2856:2862	high throughput screens	2840:2862	high throughput screens of compounds or genes that protect from photoreceptor degeneration	2840:2929	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	3	22	theme	novel	539:543	arg1	models					545:550	novel models	539:550	novel models of photoreceptor degeneration	539:580	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	22	theme	novel	539:543	arg1	mutations					513:521	precise mutations	505:521	precise mutations in zebrafish	505:534	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	1	23	theme	Retinitis	123:131	arg1	pigmentosa					133:142	Purpose Retinitis pigmentosa	115:142	Purpose Retinitis pigmentosa (RP)	115:147	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	1	23	theme	Retinitis	123:131	arg1	collection					154:163	a collection	152:163	a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness	152:278	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	1	23	theme	Retinitis	123:131	arg1	RP					145:146	RP	145:146	RP	145:146	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	16	24	theme	plasma	2538:2543	arg1	membrane					2545:2552	the plasma membrane	2534:2552	the plasma membrane	2534:2552	Following the loss of the targeting sequence, immunolabeling for Rho was no longer restricted to the rod outer segment, but it was also localized to the plasma membrane.
30210230	3	25	from	mutations	513:521	arg1	zebrafish					526:534	zebrafish	526:534	zebrafish	526:534	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	5	26	theme	restriction	991:1001	arg1	polymorphism					1019:1030	restriction fragment length polymorphism	991:1030	restriction fragment length polymorphism (RFLP)	991:1037	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	5	26	theme	restriction	991:1001	arg1	RFLP					1033:1036	RFLP	1033:1036	RFLP	1033:1036	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	7	27	theme	rod	1380:1382	arg1	photoreceptors					1384:1397	rod photoreceptors	1380:1397	rod photoreceptors	1380:1397	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	3	28	theme	rho	801:803	arg1	rh1-1					812:816	rh1-1	812:816	rh1-1	812:816	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	28	theme	rho	801:803	arg1	locus					805:809	the major zebrafish rho locus	781:809	the major zebrafish rho locus	781:809	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	14	29	theme	allele	2250:2255	arg1	recovery					2118:2125	the recovery	2114:2125	the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339	2114:2312	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	8	30	from	effect	1403:1408	arg1	cones					1413:1417	cones	1413:1417	cones	1413:1417	No effect on cones was observed.
30210230	3	31	dep	repeats	707:713	arg1	insertion					737:745	/Cas9-induced insertion	723:745	/Cas9-induced insertion	723:745	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	31	dep	repeats	707:713	arg1	mutations					768:776	deletion (indel) mutations	751:776	deletion (indel) mutations	751:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	32	theme	degeneration	569:580	arg1	models					545:550	novel models	539:550	novel models of photoreceptor degeneration	539:580	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	32	theme	degeneration	569:580	arg1	mutations					513:521	precise mutations	505:521	precise mutations in zebrafish	505:534	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	9	33	theme	rh1-1	1469:1473	arg1	sequence					1457:1464	the 5'-coding sequence	1443:1464	the 5'-coding sequence of rh1-1	1443:1473	Targeting the 5'-coding sequence of rh1-1 led to the recovery of several indels similar to disease-associated alleles.
30210230	4	34	theme	single	939:944	arg1	gRNA					957:960	gRNA	957:960	gRNA	957:960	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	4	34	theme	single	939:944	arg1	RNA					952:954	a single guide RNA	937:954	a single guide RNA (gRNA)	937:961	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	17	35	theme	gene	2601:2604	arg1	targeting					2606:2614	gene targeting	2601:2614	gene targeting	2601:2614	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	14	36	theme	second	2234:2239	arg1	allele					2250:2255	a second in-frame allele	2232:2255	a second in-frame allele that disrupted the putative phosphorylation site at S339	2232:2312	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	3	37	theme	major	785:789	arg1	rh1-1					812:816	rh1-1	812:816	rh1-1	812:816	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	37	theme	major	785:789	arg1	locus					805:809	the major zebrafish rho locus	781:809	the major zebrafish rho locus	781:809	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	5	38	theme	injected	1068:1075	arg1	embryos					1077:1083	injected embryos	1068:1083	injected embryos	1068:1083	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	16	39	theme	outer	2490:2494	arg1	segment					2496:2502	the rod outer segment	2482:2502	the rod outer segment	2482:2502	Following the loss of the targeting sequence, immunolabeling for Rho was no longer restricted to the rod outer segment, but it was also localized to the plasma membrane.
30210230	4	40	theme	transcribed	902:912	arg1	mRNA					914:917	in vitro transcribed mRNA	893:917	in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA)	893:961	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	14	41	theme	3'-coding	2076:2084	arg1	region					2086:2091	the 3'-coding region	2072:2091	the 3'-coding region of rh1-1	2072:2100	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	0	42	theme	rod	83:85	arg1	degeneration					101:112	rapid rod photoreceptor degeneration	77:112	rapid rod photoreceptor degeneration	77:112	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	15	43	theme	rod	2340:2342	arg1	death					2344:2348	rod death	2340:2348	rod death in a dominant inheritance pattern	2340:2382	Both alleles resulted in rod death in a dominant inheritance pattern.
30210230	12	44	theme	in-frame	1856:1863	arg1	mutations					1865:1873	Two in-frame mutations	1852:1873	Two in-frame mutations	1852:1873	Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15.
30210230	17	45	theme	alleles	2733:2739	arg1	isolation					2714:2722	the rapid isolation	2704:2722	the rapid isolation of novel alleles in zebrafish that phenocopy disease	2704:2775	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	14	46	theme	sorting	2211:2217	arg1	sequence					2219:2226	the conserved VSPA sorting sequence	2192:2226	the conserved VSPA sorting sequence	2192:2226	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	11	47	theme	rod	1838:1840	arg1	survival					1842:1849	rod survival	1838:1849	rod survival	1838:1849	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	0	48	theme	degeneration	101:112	arg1	models					67:72	models	67:72	models of rapid rod photoreceptor degeneration	67:112	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	0	48	theme	degeneration	101:112	arg1	locus					58:62	locus	58:62	locus	58:62	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	5	49	theme	DNA	1043:1045	arg1	analyses					1056:1063	DNA sequence analyses	1043:1063	DNA sequence analyses	1043:1063	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	9	50	theme	several	1498:1504	arg1	indels					1506:1511	several indels	1498:1511	several indels similar to disease-associated alleles	1498:1549	Targeting the 5'-coding sequence of rh1-1 led to the recovery of several indels similar to disease-associated alleles.
30210230	2	51	theme	visual	421:426	arg1	rhodopsin					436:444	the visual pigment rhodopsin	417:444	the visual pigment rhodopsin (RHO)	417:450	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	2	51	theme	visual	421:426	arg1	RHO					447:449	RHO	447:449	RHO	447:449	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	14	52	from	S339	2309:2312	arg1	site					2301:2304	the putative phosphorylation site	2272:2304	the putative phosphorylation site at S339	2272:2312	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	14	53	theme	conserved	2196:2204	arg1	sequence					2219:2226	the conserved VSPA sorting sequence	2192:2226	the conserved VSPA sorting sequence	2192:2226	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	10	54	theme	premature	1588:1596	arg1	codon					1603:1607	a premature stop codon	1586:1607	a premature stop codon (T17*)	1586:1614	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	10	54	theme	premature	1588:1596	arg1	*					1613:1613	T17*	1610:1613	T17*	1610:1613	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	0	55	theme	Targeted	0:7	arg1	disruption					9:18	Targeted disruption	0:18	Targeted disruption of the endogenous zebrafish	0:46	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	18	56	theme	in-vivo	2821:2827	arg1	models					2829:2834	much needed in-vivo models	2809:2834	much needed in-vivo models	2809:2834	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	17	57	from	zebrafish	2744:2752	arg1	isolation					2714:2722	the rapid isolation	2704:2722	the rapid isolation of novel alleles in zebrafish that phenocopy disease	2704:2775	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	9	58	theme	similar	1513:1519	arg1	indels					1506:1511	several indels	1498:1511	several indels similar to disease-associated alleles	1498:1549	Targeting the 5'-coding sequence of rh1-1 led to the recovery of several indels similar to disease-associated alleles.
30210230	18	59	theme	photoreceptor	2904:2916	arg1	degeneration					2918:2929	photoreceptor degeneration	2904:2929	photoreceptor degeneration	2904:2929	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	17	60	from	alleles	2733:2739	arg1	zebrafish					2744:2752	zebrafish	2744:2752	zebrafish that phenocopy disease	2744:2775	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	9	61	theme	disease-associated	1524:1541	arg1	alleles					1543:1549	disease-associated alleles	1524:1549	disease-associated alleles	1524:1549	Targeting the 5'-coding sequence of rh1-1 led to the recovery of several indels similar to disease-associated alleles.
30210230	10	62	theme	T17	1610:1612	arg1	codon					1603:1607	a premature stop codon	1586:1607	a premature stop codon (T17*)	1586:1614	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	10	62	theme	T17	1610:1612	arg1	*					1613:1613	T17*	1610:1613	T17*	1610:1613	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	0	63	theme	endogenous	27:36	arg1	zebrafish					38:46	the endogenous zebrafish	23:46	the endogenous zebrafish	23:46	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	7	64	theme	conserved	1251:1259	arg1	regions					1261:1267	highly conserved regions	1244:1267	highly conserved regions of rh1-1	1244:1276	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	15	65	theme	dominant	2355:2362	arg1	pattern					2376:2382	a dominant inheritance pattern	2353:2382	a dominant inheritance pattern	2353:2382	Both alleles resulted in rod death in a dominant inheritance pattern.
30210230	18	66	theme	needed	2814:2819	arg1	models					2829:2834	much needed in-vivo models	2809:2834	much needed in-vivo models	2809:2834	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	13	67	theme	heterozygous	1983:1994	arg1	Larvae					1976:1981	Larvae	1976:1981	Larvae heterozygous for either of the alleles	1976:2020	Larvae heterozygous for either of the alleles demonstrated rapid rod degeneration.
30210230	18	68	theme	compounds	2867:2875	arg1	screens					2856:2862	high throughput screens	2840:2862	high throughput screens of compounds or genes that protect from photoreceptor degeneration	2840:2929	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	2	69	from	mutations	386:394	arg1	gene					403:406	the gene	399:406	the gene encoding the visual pigment rhodopsin (RHO)	399:450	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	2	70	theme	recessive	350:358	arg1	modes					360:364	dominant or recessive modes	338:364	dominant or recessive modes of inheritance	338:379	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	3	71	dep	generation	599:608	arg1	the					595:597	the	595:597	the	595:597	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	4	72	dep	Methods	819:825	arg1	embryos					861:867	One- or two-cell staged zebrafish embryos	827:867	Methods One- or two-cell staged zebrafish embryos	819:867	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	14	73	theme	allele	2133:2138	arg1	recovery					2118:2125	the recovery	2114:2125	the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339	2114:2312	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	3	74	theme	clustered	657:665	arg1	CRISPR					716:721	CRISPR	716:721	CRISPR	716:721	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	74	theme	clustered	657:665	arg1	repeats					707:713	novel clustered regularly interspaced short palindromic repeats	651:713	novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations	651:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	2	75	theme	dominant	338:345	arg1	modes					360:364	dominant or recessive modes	338:364	dominant or recessive modes of inheritance	338:379	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	1	76	theme	cells	252:256	arg1	degeneration					206:217	the degeneration	202:217	the degeneration of light-sensitive photoreceptor cells	202:256	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	17	77	theme	rapid	2708:2712	arg1	isolation					2714:2722	the rapid isolation	2704:2722	the rapid isolation of novel alleles in zebrafish that phenocopy disease	2704:2775	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	14	78	theme	stop	2161:2164	arg1	codon					2166:2170	a premature stop codon	2149:2170	a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence	2149:2226	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	14	78	theme	stop	2161:2164	arg1	*					2177:2177	S347*	2173:2177	S347*	2173:2177	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	18	79	theme	genes	2880:2884	arg1	screens					2856:2862	high throughput screens	2840:2862	high throughput screens of compounds or genes that protect from photoreceptor degeneration	2840:2929	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	12	80	theme	glycosylation	1935:1947	arg1	sequence					1959:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15.
30210230	4	81	theme	One-	827:830	arg1	embryos					861:867	One- or two-cell staged zebrafish embryos	827:867	Methods One- or two-cell staged zebrafish embryos	819:867	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	7	82	theme	photoreceptors	1384:1397	arg1	degeneration					1364:1375	the rapid degeneration	1354:1375	the rapid degeneration of rod photoreceptors	1354:1397	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	3	83	from	generation	599:608	arg1	rh1-1					812:816	rh1-1	812:816	rh1-1	812:816	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	83	from	generation	599:608	arg1	locus					805:809	the major zebrafish rho locus	781:809	the major zebrafish rho locus	781:809	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	84	theme	palindromic	695:705	arg1	CRISPR					716:721	CRISPR	716:721	CRISPR	716:721	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	84	theme	palindromic	695:705	arg1	repeats					707:713	novel clustered regularly interspaced short palindromic repeats	651:713	novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations	651:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	16	85	theme	targeting	2411:2419	arg1	sequence					2421:2428	the targeting sequence	2407:2428	the targeting sequence	2407:2428	Following the loss of the targeting sequence, immunolabeling for Rho was no longer restricted to the rod outer segment, but it was also localized to the plasma membrane.
30210230	17	86	theme	large	2634:2638	arg1	number					2640:2645	the large number	2630:2645	the large number of mutations associated with RP	2630:2677	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	10	87	theme	frame	1554:1558	arg1	mutation					1566:1573	A frame shift mutation	1552:1573	A frame shift mutation leading to a premature stop codon (T17*)	1552:1614	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	3	88	theme	interspaced	677:687	arg1	CRISPR					716:721	CRISPR	716:721	CRISPR	716:721	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	88	theme	interspaced	677:687	arg1	repeats					707:713	novel clustered regularly interspaced short palindromic repeats	651:713	novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations	651:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	1	89	theme	genetic	168:174	arg1	disorders					176:184	genetic disorders	168:184	genetic disorders	168:184	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	13	90	theme	rapid	2035:2039	arg1	degeneration					2045:2056	rapid rod degeneration	2035:2056	rapid rod degeneration	2035:2056	Larvae heterozygous for either of the alleles demonstrated rapid rod degeneration.
30210230	7	91	theme	rapid	1358:1362	arg1	degeneration					1364:1375	the rapid degeneration	1354:1375	the rapid degeneration of rod photoreceptors	1354:1397	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	14	92	theme	putative	2276:2283	arg1	site					2301:2304	the putative phosphorylation site	2272:2304	the putative phosphorylation site at S339	2272:2312	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	3	93	theme	precise	505:511	arg1	models					545:550	novel models	539:550	novel models of photoreceptor degeneration	539:580	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	93	theme	precise	505:511	arg1	mutations					513:521	precise mutations	505:521	precise mutations in zebrafish	505:534	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	12	94	theme	conserved	1916:1924	arg1	sequence					1959:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15.
30210230	11	95	theme	Rho-specific	1719:1730	arg1	antibody					1732:1739	a Rho-specific antibody	1717:1739	a Rho-specific antibody	1717:1739	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	6	96	theme	histological	1175:1186	arg1	changes					1201:1207	histological and cellular changes	1175:1207	histological and cellular changes	1175:1207	Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes.
30210230	3	97	theme	deletion	751:758	arg1	mutations					768:776	deletion (indel) mutations	751:776	deletion (indel) mutations	751:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	1	98	theme	Purpose	115:121	arg1	pigmentosa					133:142	Purpose Retinitis pigmentosa	115:142	Purpose Retinitis pigmentosa (RP)	115:147	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	1	98	theme	Purpose	115:121	arg1	collection					154:163	a collection	152:163	a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness	152:278	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	1	98	theme	Purpose	115:121	arg1	RP					145:146	RP	145:146	RP	145:146	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	6	99	with	Immunolabeling	1100:1113	arg1	antibodies					1143:1152	rod- and cone-specific antibodies	1120:1152	rod- and cone-specific antibodies	1120:1152	Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes.
30210230	4	100	theme	two-cell	835:842	arg1	embryos					861:867	One- or two-cell staged zebrafish embryos	827:867	Methods One- or two-cell staged zebrafish embryos	819:867	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	9	101	theme	5'-coding	1447:1455	arg1	sequence					1457:1464	the 5'-coding sequence	1443:1464	the 5'-coding sequence of rh1-1	1443:1473	Targeting the 5'-coding sequence of rh1-1 led to the recovery of several indels similar to disease-associated alleles.
30210230	4	102	theme	zebrafish	851:859	arg1	embryos					861:867	One- or two-cell staged zebrafish embryos	827:867	Methods One- or two-cell staged zebrafish embryos	819:867	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	7	103	theme	recessive	1304:1312	arg1	alleles					1314:1320	dominant and recessive alleles	1291:1320	dominant and recessive alleles	1291:1320	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	11	104	theme	fluorescence	1690:1701	arg1	labeling					1703:1710	fluorescence labeling	1690:1710	fluorescence labeling with a Rho-specific antibody	1690:1739	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	5	105	theme	fragment	1003:1010	arg1	polymorphism					1019:1030	restriction fragment length polymorphism	991:1030	restriction fragment length polymorphism (RFLP)	991:1037	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	5	105	theme	fragment	1003:1010	arg1	RFLP					1033:1036	RFLP	1033:1036	RFLP	1033:1036	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	3	106	theme	photoreceptor	555:567	arg1	degeneration					569:580	photoreceptor degeneration	555:580	photoreceptor degeneration	555:580	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	11	107	with	Immunoblot	1675:1684	arg1	antibody					1732:1739	a Rho-specific antibody	1717:1739	a Rho-specific antibody	1717:1739	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	16	108	theme	rod	2486:2488	arg1	segment					2496:2502	the rod outer segment	2482:2502	the rod outer segment	2482:2502	Following the loss of the targeting sequence, immunolabeling for Rho was no longer restricted to the rod outer segment, but it was also localized to the plasma membrane.
30210230	7	109	theme	dominant	1291:1298	arg1	alleles					1314:1320	dominant and recessive alleles	1291:1320	dominant and recessive alleles	1291:1320	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	14	110	theme	in-frame	2241:2248	arg1	allele					2250:2255	a second in-frame allele	2232:2255	a second in-frame allele that disrupted the putative phosphorylation site at S339	2232:2312	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	3	111	theme	indel	761:765	arg1	mutations					768:776	deletion (indel) mutations	751:776	deletion (indel) mutations	751:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	0	112	theme	rapid	77:81	arg1	degeneration					101:112	rapid rod photoreceptor degeneration	77:112	rapid rod photoreceptor degeneration	77:112	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	15	113	theme	inheritance	2364:2374	arg1	pattern					2376:2382	a dominant inheritance pattern	2353:2382	a dominant inheritance pattern	2353:2382	Both alleles resulted in rod death in a dominant inheritance pattern.
30210230	14	114	theme	region	2086:2091	arg1	Targeting					2059:2067	Targeting	2059:2067	Targeting of the 3'-coding region of rh1-1	2059:2100	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	3	115	theme	zebrafish	791:799	arg1	rh1-1					812:816	rh1-1	812:816	rh1-1	812:816	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	115	theme	zebrafish	791:799	arg1	locus					805:809	the major zebrafish rho locus	781:809	the major zebrafish rho locus	781:809	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	0	116	theme	photoreceptor	87:99	arg1	degeneration					101:112	rapid rod photoreceptor degeneration	77:112	rapid rod photoreceptor degeneration	77:112	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	13	117	theme	rod	2041:2043	arg1	degeneration					2045:2056	rapid rod degeneration	2035:2056	rapid rod degeneration	2035:2056	Larvae heterozygous for either of the alleles demonstrated rapid rod degeneration.
30210230	17	118	theme	novel	2727:2731	arg1	alleles					2733:2739	novel alleles	2727:2739	novel alleles in zebrafish that phenocopy disease	2727:2775	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	14	119	theme	sequence	2219:2226	arg1	upstream					2180:2187	upstream	2180:2187	upstream	2180:2187	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	18	120	theme	novel	2784:2788	arg1	lines					2790:2794	These novel lines	2778:2794	These novel lines	2778:2794	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	2	121	theme	frequent	465:472	arg1	cause					474:478	the most frequent cause	456:478	the most frequent cause	456:478	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	2	121	theme	frequent	465:472	arg1	mutations					386:394	mutations	386:394	mutations in the gene encoding the visual pigment rhodopsin (RHO)	386:450	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	14	122	theme	VSPA	2206:2209	arg1	sequence					2219:2226	the conserved VSPA sorting sequence	2192:2226	the conserved VSPA sorting sequence	2192:2226	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	2	123	theme	inheritance	369:379	arg1	modes					360:364	dominant or recessive modes	338:364	dominant or recessive modes of inheritance	338:379	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	5	124	theme	sequence	1047:1054	arg1	analyses					1056:1063	DNA sequence analyses	1043:1063	DNA sequence analyses	1043:1063	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	9	125	theme	indels	1506:1511	arg1	recovery					1486:1493	the recovery	1482:1493	the recovery of several indels similar to disease-associated alleles	1482:1549	Targeting the 5'-coding sequence of rh1-1 led to the recovery of several indels similar to disease-associated alleles.
30210230	7	126	theme	rh1-1	1272:1276	arg1	regions					1261:1267	highly conserved regions	1244:1267	highly conserved regions of rh1-1	1244:1276	Results Using gRNAs that targeted highly conserved regions of rh1-1, a series of dominant and recessive alleles were recovered that resulted in the rapid degeneration of rod photoreceptors.
30210230	15	127	from	death	2344:2348	arg1	pattern					2376:2382	a dominant inheritance pattern	2353:2382	a dominant inheritance pattern	2353:2382	Both alleles resulted in rod death in a dominant inheritance pattern.
30210230	14	128	theme	upstream	2180:2187	arg1	codon					2166:2170	a premature stop codon	2149:2170	a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence	2149:2226	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	14	128	theme	upstream	2180:2187	arg1	*					2177:2177	S347*	2173:2177	S347*	2173:2177	Targeting of the 3'-coding region of rh1-1 resulted in the recovery of an allele encoding a premature stop codon (S347*) upstream of the conserved VSPA sorting sequence and a second in-frame allele that disrupted the putative phosphorylation site at S339.
30210230	0	129	theme	zebrafish	38:46	arg1	disruption					9:18	Targeted disruption	0:18	Targeted disruption of the endogenous zebrafish	0:46	Targeted disruption of the endogenous zebrafish rhodopsin locus as models of rapid rod photoreceptor degeneration.
30210230	16	130	theme	sequence	2421:2428	arg1	loss					2399:2402	the loss	2395:2402	the loss of the targeting sequence	2395:2428	Following the loss of the targeting sequence, immunolabeling for Rho was no longer restricted to the rod outer segment, but it was also localized to the plasma membrane.
30210230	4	131	theme	guide	946:950	arg1	gRNA					957:960	gRNA	957:960	gRNA	957:960	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	4	131	theme	guide	946:950	arg1	RNA					952:954	a single guide RNA	937:954	a single guide RNA (gRNA)	937:961	Methods One- or two-cell staged zebrafish embryos were microinjected with in vitro transcribed mRNA encoding Cas9 and a single guide RNA (gRNA).
30210230	1	132	theme	light-sensitive	222:236	arg1	cells					252:256	light-sensitive photoreceptor cells	222:256	light-sensitive photoreceptor cells	222:256	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30210230	5	133	from	polymorphism	1019:1030	arg1	offspring					1089:1097	offspring	1089:1097	offspring	1089:1097	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	5	133	from	polymorphism	1019:1030	arg1	embryos					1077:1083	injected embryos	1068:1083	injected embryos	1068:1083	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	5	134	from	analyses	1056:1063	arg1	offspring					1089:1097	offspring	1089:1097	offspring	1089:1097	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	5	134	from	analyses	1056:1063	arg1	embryos					1077:1083	injected embryos	1068:1083	injected embryos	1068:1083	Mutations were detected by restriction fragment length polymorphism (RFLP) and DNA sequence analyses in injected embryos and offspring.
30210230	11	135	theme	null	1771:1774	arg1	allele					1776:1781	a null allele	1769:1781	a null allele	1769:1781	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	11	135	theme	null	1771:1774	arg1	this					1754:1757	this	1754:1757	this	1754:1757	Immunoblot and fluorescence labeling with a Rho-specific antibody suggest that this is indeed a null allele, illustrating that the Rho expression is essential for rod survival.
30210230	2	136	theme	pigment	428:434	arg1	rhodopsin					436:444	the visual pigment rhodopsin	417:444	the visual pigment rhodopsin (RHO)	417:450	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	2	136	theme	pigment	428:434	arg1	RHO					447:449	RHO	447:449	RHO	447:449	RP is associated with more than 70 loci that may display dominant or recessive modes of inheritance, but mutations in the gene encoding the visual pigment rhodopsin (RHO) are the most frequent cause.
30210230	10	137	theme	rod	1628:1630	arg1	degeneration					1632:1643	rod degeneration	1628:1643	rod degeneration	1628:1643	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	17	138	from	isolation	2714:2722	arg1	zebrafish					2744:2752	zebrafish	2744:2752	zebrafish that phenocopy disease	2744:2775	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	3	139	theme	germline	614:621	arg1	transmission					623:634	germline transmission	614:634	germline transmission	614:634	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	12	140	link	N-linked	1926:1933	arg1	sequence					1959:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	the highly conserved N-linked glycosylation consensus sequence	1905:1966	Two in-frame mutations were recovered that disrupted the highly conserved N-linked glycosylation consensus sequence at N15.
30210230	6	141	used	used	1158:1161	arg2	Immunolabeling					1100:1113	Immunolabeling	1100:1113	Immunolabeling with rod- and cone-specific antibodies	1100:1152	Immunolabeling with rod- and cone-specific antibodies was used to test for histological and cellular changes.
30210230	10	142	theme	stop	1598:1601	arg1	codon					1603:1607	a premature stop codon	1586:1607	a premature stop codon (T17*)	1586:1614	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	10	142	theme	stop	1598:1601	arg1	*					1613:1613	T17*	1610:1613	T17*	1610:1613	A frame shift mutation leading to a premature stop codon (T17*) resulted in rod degeneration when brought to homozygosity.
30210230	3	143	from	transmission	623:634	arg1	rh1-1					812:816	rh1-1	812:816	rh1-1	812:816	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	143	from	transmission	623:634	arg1	locus					805:809	the major zebrafish rho locus	781:809	the major zebrafish rho locus	781:809	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	144	theme	novel	651:655	arg1	CRISPR					716:721	CRISPR	716:721	CRISPR	716:721	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	3	144	theme	novel	651:655	arg1	repeats					707:713	novel clustered regularly interspaced short palindromic repeats	651:713	novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations	651:776	In an effort to develop precise mutations in zebrafish as novel models of photoreceptor degeneration, we describe the generation and germline transmission of a series of novel clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-induced insertion and deletion (indel) mutations in the major zebrafish rho locus, rh1-1.
30210230	18	145	theme	throughput	2845:2854	arg1	screens					2856:2862	high throughput screens	2840:2862	high throughput screens of compounds or genes that protect from photoreceptor degeneration	2840:2929	These novel lines will provide much needed in-vivo models for high throughput screens of compounds or genes that protect from photoreceptor degeneration.
30210230	17	146	theme	mutations	2650:2658	arg1	number					2640:2645	the large number	2630:2645	the large number of mutations associated with RP	2630:2677	Conclusions The efficiency of CRISPR/Cas9 for gene targeting, coupled with the large number of mutations associated with RP, provided a backdrop for the rapid isolation of novel alleles in zebrafish that phenocopy disease.
30210230	1	147	theme	photoreceptor	238:250	arg1	cells					252:256	light-sensitive photoreceptor cells	222:256	light-sensitive photoreceptor cells	222:256	Purpose Retinitis pigmentosa (RP) is a collection of genetic disorders that results in the degeneration of light-sensitive photoreceptor cells, leading to blindness.
30105014	3	0	theme	A549	1005:1008	arg1	line					1015:1018	A549 cell line	1005:1018	A549 cell line	1005:1018	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	8	1	theme	subtype-specific	2015:2030	arg1	manner					2032:2037	a IAV subtype-specific manner	2009:2037	a IAV subtype-specific manner	2009:2037	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	2	2	theme	entry	712:716	arg1	fragment					621:628	a recombinant fragment	607:628	a recombinant fragment	607:628	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	2	theme	entry	712:716	arg1	inhibitor					718:726	an entry inhibitor	709:726	an entry inhibitor of IAV	709:733	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	2	theme	entry	712:716	arg1	expression					756:765	M1 expression	753:765	M1 expression	753:765	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	9	3	theme	pro-inflammatory	2081:2096	arg1	milieu					2098:2103	pro-inflammatory milieu	2081:2103	pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage	2081:2220	Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
30105014	0	4	theme	A	316:316	arg1	virus					318:322	influenza A virus	306:322	influenza A virus (IAV)	306:328	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	4	theme	A	316:316	arg1	IAV					325:327	IAV	325:327	IAV	325:327	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	1	5	theme	carbohydrate	498:509	arg1	patterns					511:518	carbohydrate patterns	498:518	carbohydrate patterns (N-linked mannosylated)	498:542	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	3	6	theme	mRNA	893:896	arg1	levels					898:903	mRNA levels	893:903	mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES	893:944	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	1	7	theme	neuraminidase	413:425	arg1	activity					432:439	neuraminidase (NA) activity	413:439	neuraminidase (NA) activity	413:439	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	1	8	theme	IAV	576:578	arg1	NA					547:548	NA	547:548	NA	547:548	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	1	8	theme	IAV	576:578	arg1	HA					569:570	HA	569:570	HA	569:570	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	1	8	theme	IAV	576:578	arg1	hemagglutinin					554:566	hemagglutinin	554:566	hemagglutinin (HA) of IAV	554:578	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	7	9	theme	pH1N1	1594:1598	arg1	case					1586:1589	the case	1582:1589	the case of pH1N1	1582:1598	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	2	10	theme	CRD	688:690	arg1	regions					692:698	CRD regions	688:698	CRD regions	688:698	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	8	11	theme	SP-D	1965:1968	arg1	effect					1955:1960	immunomodulatory effect	1938:1960	immunomodulatory effect of SP-D on host cells	1938:1982	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	0	12	theme	Surfactant	121:130	arg1	Protein					132:138	a Recombinant Truncated Surfactant Protein	97:138	a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D)	97:169	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	9	13	theme	aberrant	2145:2152	arg1	recruitment					2172:2182	aberrant inflammatory cell recruitment	2145:2182	aberrant inflammatory cell recruitment leading to cell death and lung damage	2145:2220	Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
30105014	6	14	theme	dramatic	1508:1515	arg1	suppression					1517:1527	a dramatic suppression	1506:1527	a dramatic suppression of key pro-inflammatory cytokines and chemokines	1506:1576	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	8	15	theme	immunomodulatory	1938:1953	arg1	effect					1955:1960	immunomodulatory effect	1938:1960	immunomodulatory effect of SP-D on host cells	1938:1982	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	0	16	theme	protein	154:160	arg1	D					162:162	Surfactant protein D	143:162	a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D)	97:169	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	16	theme	protein	154:160	arg1	SP-D					165:168	SP-D	165:168	SP-D	165:168	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	9	17	theme	cell	2167:2170	arg1	recruitment					2172:2182	aberrant inflammatory cell recruitment	2145:2182	aberrant inflammatory cell recruitment leading to cell death and lung damage	2145:2220	Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
30105014	6	18	theme	Multiplex	1413:1421	arg1	array					1432:1436	Multiplex cytokine array	1413:1436	Multiplex cytokine array	1413:1436	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	7	19	theme	H3N2	1830:1833	arg1	subtype					1835:1841	H3N2 subtype	1830:1841	H3N2 subtype	1830:1841	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	1	20	theme	IAV	384:386	arg1	hemagglutination					348:363	hemagglutination	348:363	hemagglutination	348:363	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	1	20	theme	IAV	384:386	arg1	infectivity					369:379	infectivity	369:379	infectivity	369:379	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	0	21	theme	pathogens	285:293	arg1	virus					318:322	influenza A virus	306:322	influenza A virus (IAV)	306:328	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	21	theme	pathogens	285:293	arg1	pathogens					285:293	pathogens	285:293	pathogens	285:293	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	21	theme	pathogens	285:293	arg1	variety					274:280	a variety	272:280	a variety of pathogens, including influenza A virus (IAV)	272:328	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	6	22	theme	cells	1493:1497	arg1	treatment					1460:1468	rfhSP-D treatment	1452:1468	rfhSP-D treatment of IAV challenged A549 cells	1452:1497	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	1	23	link	N-linked	521:528	arg1	mannosylated					530:541	mannosylated	530:541	mannosylated	530:541	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	9	24	theme	cell	2195:2198	arg1	death					2200:2204	cell death	2195:2204	cell death	2195:2204	Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
30105014	0	25	dep	D.	140:141	arg1	D					162:162	Surfactant protein D	143:162	a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D)	97:169	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	25	dep	D.	140:141	arg1	SP-D					165:168	SP-D	165:168	SP-D	165:168	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	2	26	theme	human	633:637	arg1	SP-D					639:642	human SP-D	633:642	human SP-D (rfhSP-D)	633:652	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	26	theme	human	633:637	arg1	rfhSP-D					645:651	rfhSP-D	645:651	rfhSP-D	645:651	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	0	27	theme	A	86:86	arg1	Virus					88:92	Influenza A Virus	76:92	Influenza A Virus	76:92	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	7	28	theme	suppressive	1735:1745	arg1	effects					1747:1753	these suppressive effects	1729:1753	these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40)	1729:1793	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	0	29	theme	lung	216:219	arg1	secretion					199:207	the mucosal secretion	187:207	the mucosal secretion of the lung	187:219	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	5	30	theme	suggestive	1325:1334	arg1	rfhSP-D					1316:1322	10 µg/ml rfhSP-D	1307:1322	10 µg/ml rfhSP-D	1307:1322	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	4	31	theme	Darby	1073:1077	arg1	MDCK					1094:1097	MDCK	1094:1097	MDCK	1094:1097	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	4	31	theme	Darby	1073:1077	arg1	kidney					1086:1091	Madin Darby canine kidney	1067:1091	Madin Darby canine kidney (MDCK) cells	1067:1104	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	7	32	from	case	1822:1825	arg1	evident					1807:1813	evident	1807:1813	evident	1807:1813	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	4	33	theme	kidney	1086:1091	arg1	cells					1100:1104	Madin Darby canine kidney (MDCK) cells	1067:1104	Madin Darby canine kidney (MDCK) cells	1067:1104	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	0	34	theme	Recombinant	99:109	arg1	Protein					132:138	a Recombinant Truncated Surfactant Protein	97:138	a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D)	97:169	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	8	35	from	extent	1928:1933	arg1	cells					1978:1982	host cells	1973:1982	host cells	1973:1982	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	6	36	theme	pro-inflammatory	1536:1551	arg1	cytokines					1553:1561	key pro-inflammatory cytokines	1532:1561	key pro-inflammatory cytokines	1532:1561	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	4	37	theme	IAV	1050:1052	arg1	infection					1054:1062	IAV infection	1050:1062	IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding	1050:1123	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	5	38	theme	reporter	1178:1185	arg1	activity					1187:1194	luciferase reporter activity	1167:1194	luciferase reporter activity	1167:1194	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	0	39	theme	Entry	0:4	arg1	Inhibition					6:15	Entry Inhibition	0:15	Entry Inhibition	0:15	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	3	40	theme	RANTES	939:944	arg1	levels					898:903	mRNA levels	893:903	mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES	893:944	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	0	41	theme	host	251:254	arg1	defense					256:262	the innate host defense	240:262	the innate host defense against a variety of pathogens, including influenza A virus (IAV)	240:328	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	5	42	theme	rfhSP-D	1358:1364	arg1	role					1350:1353	a critical role	1339:1353	a critical role of rfhSP-D as an entry inhibitor against IAV infectivity	1339:1410	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	8	43	from	effect	1955:1960	arg1	cells					1978:1982	host cells	1973:1982	host cells	1973:1982	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	2	44	contain	containing	655:664	arg1	fragment					621:628	a recombinant fragment	607:628	a recombinant fragment	607:628	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	44	contain	containing	655:664	arg2	regions					692:698	CRD regions	688:698	CRD regions	688:698	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	44	contain	containing	655:664	arg1	expression					756:765	M1 expression	753:765	M1 expression	753:765	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	44	contain	containing	655:664	arg2	neck					679:682	homotrimeric neck	666:682	homotrimeric neck	666:682	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	44	contain	containing	655:664	arg1	inhibitor					718:726	an entry inhibitor	709:726	an entry inhibitor of IAV	709:733	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	4	45	theme	HA	1114:1115	arg1	binding					1117:1123	HA binding	1114:1123	HA binding	1114:1123	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	2	46	theme	H3N2	826:829	arg1	subtypes					831:838	H1N1 and H3N2 subtypes	817:838	H1N1 and H3N2 subtypes	817:838	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	0	47	theme	Immune	52:57	arg1	Response					59:66	Pro-Inflammatory Immune Response	35:66	Pro-Inflammatory Immune Response Against Influenza A Virus	35:92	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	2	48	theme	H1N1	817:820	arg1	subtypes					831:838	H1N1 and H3N2 subtypes	817:838	H1N1 and H3N2 subtypes	817:838	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	5	49	theme	role	1350:1353	arg1	suggestive					1325:1334	suggestive	1325:1334	suggestive	1325:1334	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	5	50	theme	lentiviral	1244:1253	arg1	particles					1255:1263	H1+N1 pseudotyped lentiviral particles	1226:1263	H1+N1 pseudotyped lentiviral particles	1226:1263	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	1	51	theme	carbohydrate	449:460	arg1	binding					487:493	its carbohydrate recognition domain (CRD) binding	445:493	its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV	445:578	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	3	52	theme	IAV	988:990	arg1	infection					992:1000	IAV infection	988:1000	IAV infection of A549 cell line	988:1018	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	8	53	theme	IAV	2011:2013	arg1	manner					2032:2037	a IAV subtype-specific manner	2009:2037	a IAV subtype-specific manner	2009:2037	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	2	54	theme	M1	753:754	arg1	fragment					621:628	a recombinant fragment	607:628	a recombinant fragment	607:628	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	54	theme	M1	753:754	arg1	inhibitor					718:726	an entry inhibitor	709:726	an entry inhibitor of IAV	709:733	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	54	theme	M1	753:754	arg1	expression					756:765	M1 expression	753:765	M1 expression	753:765	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	4	55	theme	cells	1100:1104	arg1	infection					1054:1062	IAV infection	1050:1062	IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding	1050:1123	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	7	56	theme	GM-CSF	1884:1889	arg1	exception					1853:1861	the exception	1849:1861	the exception of TNF-α, IFN-α, and GM-CSF	1849:1889	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	1	57	theme	domain	474:479	arg1	binding					487:493	its carbohydrate recognition domain (CRD) binding	445:493	its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV	445:578	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	7	58	from	effects	1747:1753	arg1	IL-10					1758:1762	IL-10	1758:1762	IL-10	1758:1762	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	7	58	from	effects	1747:1753	arg1	p40					1790:1792	p40	1790:1792	p40	1790:1792	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	7	58	from	effects	1747:1753	arg1	IL-12					1783:1787	IL-12	1783:1787	IL-12 (p40)	1783:1793	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	7	58	from	effects	1747:1753	arg1	eotaxin					1771:1777	eotaxin	1771:1777	eotaxin	1771:1777	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	7	58	from	effects	1747:1753	arg1	VEGF					1765:1768	VEGF	1765:1768	VEGF	1765:1768	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	1	59	dep	patterns	511:518	arg1	mannosylated					530:541	mannosylated	530:541	mannosylated	530:541	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	2	60	theme	IAV	731:733	arg1	fragment					621:628	a recombinant fragment	607:628	a recombinant fragment	607:628	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	60	theme	IAV	731:733	arg1	inhibitor					718:726	an entry inhibitor	709:726	an entry inhibitor of IAV	709:733	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	60	theme	IAV	731:733	arg1	expression					756:765	M1 expression	753:765	M1 expression	753:765	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	1	61	theme	CRD	482:484	arg1	binding					487:493	its carbohydrate recognition domain (CRD) binding	445:493	its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV	445:578	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	3	62	theme	cell	1010:1013	arg1	line					1015:1018	A549 cell line	1005:1018	A549 cell line	1005:1018	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	2	63	theme	A549	783:786	arg1	cells					788:792	A549 cells	783:792	A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment	783:855	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	64	theme	homotrimeric	666:677	arg1	neck					679:682	homotrimeric neck	666:682	homotrimeric neck	666:682	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	5	65	theme	IAV	1396:1398	arg1	infectivity					1400:1410	IAV infectivity	1396:1410	IAV infectivity	1396:1410	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	0	66	theme	mucosal	191:197	arg1	secretion					199:207	the mucosal secretion	187:207	the mucosal secretion of the lung	187:219	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	5	67	theme	reduction	1279:1287	arg1	%					1274:1274	50%	1272:1274	50% of reduction	1272:1287	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	5	67	theme	reduction	1279:1287	arg1	reduction					1279:1287	reduction	1279:1287	reduction	1279:1287	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	0	68	theme	influenza	306:314	arg1	virus					318:322	influenza A virus	306:322	influenza A virus (IAV)	306:328	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	68	theme	influenza	306:314	arg1	IAV					325:327	IAV	325:327	IAV	325:327	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	3	69	theme	IFN-α	915:919	arg1	levels					898:903	mRNA levels	893:903	mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES	893:944	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	3	70	theme	TNF-α	908:912	arg1	levels					898:903	mRNA levels	893:903	mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES	893:944	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	7	71	theme	IFN-α	1873:1877	arg1	exception					1853:1861	the exception	1849:1861	the exception of TNF-α, IFN-α, and GM-CSF	1849:1889	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	6	72	theme	A549	1488:1491	arg1	cells					1493:1497	IAV challenged A549 cells	1473:1497	IAV challenged A549 cells	1473:1497	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	6	73	theme	key	1532:1534	arg1	cytokines					1553:1561	key pro-inflammatory cytokines	1532:1561	key pro-inflammatory cytokines	1532:1561	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	7	74	theme	TNF-α	1866:1870	arg1	exception					1853:1861	the exception	1849:1861	the exception of TNF-α, IFN-α, and GM-CSF	1849:1889	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	0	75	theme	Surfactant	143:152	arg1	D					162:162	Surfactant protein D	143:162	a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D)	97:169	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	75	theme	Surfactant	143:152	arg1	SP-D					165:168	SP-D	165:168	SP-D	165:168	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	9	76	theme	inflammatory	2154:2165	arg1	recruitment					2172:2182	aberrant inflammatory cell recruitment	2145:2182	aberrant inflammatory cell recruitment leading to cell death and lung damage	2145:2220	Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
30105014	6	77	theme	cytokine	1423:1430	arg1	array					1432:1436	Multiplex cytokine array	1413:1436	Multiplex cytokine array	1413:1436	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	2	78	theme	recombinant	609:619	arg1	fragment					621:628	a recombinant fragment	607:628	a recombinant fragment	607:628	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	78	theme	recombinant	609:619	arg1	inhibitor					718:726	an entry inhibitor	709:726	an entry inhibitor of IAV	709:733	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	78	theme	recombinant	609:619	arg1	expression					756:765	M1 expression	753:765	M1 expression	753:765	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	9	79	theme	lung	2210:2213	arg1	damage					2215:2220	lung damage	2210:2220	lung damage	2210:2220	Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
30105014	1	80	dep	reducing	404:411	arg1	addition					392:399	addition	392:399	addition	392:399	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	5	81	theme	pseudotyped	1232:1242	arg1	particles					1255:1263	H1+N1 pseudotyped lentiviral particles	1226:1263	H1+N1 pseudotyped lentiviral particles	1226:1263	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	8	82	theme	effect	1955:1960	arg1	extent					1928:1933	the extent	1924:1933	the extent of immunomodulatory effect of SP-D on host cells	1924:1982	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	7	83	theme	subtype	1835:1841	arg1	case					1822:1825	the case	1818:1825	the case of H3N2 subtype	1818:1841	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	0	84	theme	Influenza	76:84	arg1	Virus					88:92	Influenza A Virus	76:92	Influenza A Virus	76:92	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	1	85	from	binding	487:493	arg1	NA					547:548	NA	547:548	NA	547:548	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	1	85	from	binding	487:493	arg1	HA					569:570	HA	569:570	HA	569:570	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	1	85	from	binding	487:493	arg1	hemagglutinin					554:566	hemagglutinin	554:566	hemagglutinin (HA) of IAV	554:578	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	2	86	theme	SP-D	639:642	arg1	fragment					621:628	a recombinant fragment	607:628	a recombinant fragment	607:628	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	86	theme	SP-D	639:642	arg1	inhibitor					718:726	an entry inhibitor	709:726	an entry inhibitor of IAV	709:733	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	2	86	theme	SP-D	639:642	arg1	expression					756:765	M1 expression	753:765	M1 expression	753:765	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	3	87	theme	IL-6	929:932	arg1	levels					898:903	mRNA levels	893:903	mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES	893:944	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	8	88	from	cells	1978:1982	arg1	extent					1928:1933	the extent	1924:1933	the extent of immunomodulatory effect of SP-D on host cells	1924:1982	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	2	89	theme	2 h	843:845	arg1	treatment					847:855	2 h treatment	843:855	2 h treatment	843:855	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	4	90	theme	canine	1079:1084	arg1	MDCK					1094:1097	MDCK	1094:1097	MDCK	1094:1097	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	4	90	theme	canine	1079:1084	arg1	kidney					1086:1091	Madin Darby canine kidney	1067:1091	Madin Darby canine kidney (MDCK) cells	1067:1104	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	3	91	theme	IFN-β	922:926	arg1	levels					898:903	mRNA levels	893:903	mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES	893:944	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	6	92	theme	challenged	1477:1486	arg1	cells					1493:1497	IAV challenged A549 cells	1473:1497	IAV challenged A549 cells	1473:1497	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	6	93	theme	chemokines	1567:1576	arg1	suppression					1517:1527	a dramatic suppression	1506:1527	a dramatic suppression of key pro-inflammatory cytokines and chemokines	1506:1576	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	0	94	theme	Truncated	111:119	arg1	Protein					132:138	a Recombinant Truncated Surfactant Protein	97:138	a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D)	97:169	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	6	95	theme	cytokines	1553:1561	arg1	suppression					1517:1527	a dramatic suppression	1506:1527	a dramatic suppression of key pro-inflammatory cytokines and chemokines	1506:1576	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	5	96	theme	luciferase	1167:1176	arg1	activity					1187:1194	luciferase reporter activity	1167:1194	luciferase reporter activity	1167:1194	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	7	97	theme	rfhSP-D	1693:1699	arg1	treatment					1701:1709	rfhSP-D treatment	1693:1709	rfhSP-D treatment	1693:1709	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	6	98	theme	rfhSP-D	1452:1458	arg1	treatment					1460:1468	rfhSP-D treatment	1452:1468	rfhSP-D treatment of IAV challenged A549 cells	1452:1497	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	5	99	theme	10 µg/ml	1307:1314	arg1	rfhSP-D					1316:1322	10 µg/ml rfhSP-D	1307:1322	10 µg/ml rfhSP-D	1307:1322	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	4	100	theme	Madin	1067:1071	arg1	MDCK					1094:1097	MDCK	1094:1097	MDCK	1094:1097	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	4	100	theme	Madin	1067:1071	arg1	kidney					1086:1091	Madin Darby canine kidney	1067:1091	Madin Darby canine kidney (MDCK) cells	1067:1104	rfhSP-D also interfered with IAV infection of Madin Darby canine kidney (MDCK) cells through HA binding.
30105014	3	101	theme	initial	971:977	arg1	stage					979:983	the initial stage	967:983	the initial stage of IAV infection of A549 cell line	967:1018	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	0	102	theme	innate	244:249	arg1	defense					256:262	the innate host defense	240:262	the innate host defense against a variety of pathogens, including influenza A virus (IAV)	240:328	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	2	103	from	treatment	847:855	arg1	IAV					810:812	IAV	810:812	IAV of H1N1 and H3N2 subtypes at 2 h treatment	810:855	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	0	104	theme	Pro-Inflammatory	35:50	arg1	Response					59:66	Pro-Inflammatory Immune Response	35:66	Pro-Inflammatory Immune Response Against Influenza A Virus	35:92	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	8	105	theme	host	1973:1976	arg1	cells					1978:1982	host cells	1973:1982	host cells	1973:1982	These data seem to suggest that the extent of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV subtype-specific manner.
30105014	6	106	dep	challenged	1477:1486	arg1	IAV					1473:1475	IAV	1473:1475	IAV	1473:1475	Multiplex cytokine array revealed that rfhSP-D treatment of IAV challenged A549 cells led to a dramatic suppression of key pro-inflammatory cytokines and chemokines.
30105014	2	107	theme	subtypes	831:838	arg1	IAV					810:812	IAV	810:812	IAV of H1N1 and H3N2 subtypes at 2 h treatment	810:855	Here, we demonstrate that a recombinant fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions, acts as an entry inhibitor of IAV and downregulates M1 expression considerably in A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment.
30105014	5	108	theme	entry	1372:1376	arg1	inhibitor					1378:1386	an entry inhibitor	1369:1386	an entry inhibitor against IAV infectivity	1369:1410	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	0	109	theme	Response	59:66	arg1	Modulation					21:30	Modulation	21:30	Modulation	21:30	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	0	109	theme	Response	59:66	arg1	Inhibition					6:15	Entry Inhibition	0:15	Entry Inhibition	0:15	Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against Influenza A Virus by a Recombinant Truncated Surfactant Protein D. Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and contributes to the innate host defense against a variety of pathogens, including influenza A virus (IAV).
30105014	3	110	theme	infection	992:1000	arg1	stage					979:983	the initial stage	967:983	the initial stage of IAV infection of A549 cell line	967:1018	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	7	111	dep	24 h.	1714:1718	arg1	evident					1807:1813	evident	1807:1813	evident	1807:1813	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	5	112	theme	critical	1341:1348	arg1	role					1350:1353	a critical role	1339:1353	a critical role of rfhSP-D as an entry inhibitor against IAV infectivity	1339:1410	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	5	113	theme	H1+N1	1226:1230	arg1	particles					1255:1263	H1+N1 pseudotyped lentiviral particles	1226:1263	H1+N1 pseudotyped lentiviral particles	1226:1263	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	1	114	theme	recognition	462:472	arg1	binding					487:493	its carbohydrate recognition domain (CRD) binding	445:493	its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV	445:578	SP-D can inhibit hemagglutination and infectivity of IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated) on NA and hemagglutinin (HA) of IAV.
30105014	3	115	theme	line	1015:1018	arg1	infection					992:1000	IAV infection	988:1000	IAV infection of A549 cell line	988:1018	In addition, rfhSP-D downregulated mRNA levels of TNF-α, IFN-α, IFN-β, IL-6, and RANTES, particularly during the initial stage of IAV infection of A549 cell line.
30105014	7	116	from	evident	1807:1813	arg1	case					1822:1825	the case	1818:1825	the case of H3N2 subtype	1818:1841	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	7	117	with	evident	1807:1813	arg1	exception					1853:1861	the exception	1849:1861	the exception of TNF-α, IFN-α, and GM-CSF	1849:1889	In the case of pH1N1, TNF-α, IFN-α, IL-10, IL-12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception of TNF-α, IFN-α, and GM-CSF.
30105014	5	118	theme	MDCK	1199:1202	arg1	cells					1204:1208	MDCK cells	1199:1208	MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity	1199:1410	Furthermore, rfhSP-D was found to reduce luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped lentiviral particles, where 50% of reduction was observed with 10 µg/ml rfhSP-D, suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV infectivity.
30105014	9	119	theme	rfhSP-D	2046:2052	arg1	treatment					2054:2062	rfhSP-D treatment	2046:2062	rfhSP-D treatment	2046:2062	Thus, rfhSP-D treatment can downregulate pro-inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory cell recruitment leading to cell death and lung damage.
29997173	6	0	theme	immunoreceptor	1258:1271	arg1	motif					1299:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif	1240:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10	1240:1316	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	1	1	theme	Ig-like	288:294	arg1	lectin					296:301	sialic acid-binding Ig-like lectin	268:301	sialic acid-binding Ig-like lectin	268:301	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	1	1	theme	Ig-like	288:294	arg1	Siglec					260:265	the Siglec	256:265	the Siglec (sialic acid-binding Ig-like lectin)	256:302	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	5	2	theme	cell	998:1001	arg1	TCR					1013:1015	TCR	1013:1015	TCR	1013:1015	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	5	2	theme	cell	998:1001	arg1	receptor					1003:1010	the T cell receptor	992:1010	the T cell receptor (TCR)	992:1016	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	7	3	theme	CD52	1485:1488	arg1	agent					1507:1511	a therapeutic agent	1493:1511	a therapeutic agent	1493:1511	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	7	3	theme	CD52	1485:1488	arg1	potential					1464:1472	the potential	1460:1472	the potential of soluble CD52	1460:1488	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	2	4	theme	cell	406:409	arg1	suppression					411:421	T cell suppression	404:421	T cell suppression	404:421	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	6	5	theme	proinflammatory	1125:1139	arg1	B					1145:1145	its proinflammatory Box B	1121:1145	its proinflammatory Box B	1121:1145	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	6	6	with	interaction	1326:1336	arg1	TCR					1347:1349	the TCR	1343:1349	the TCR	1343:1349	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	7	7	theme	therapeutic	1495:1505	arg1	agent					1507:1511	a therapeutic agent	1493:1511	a therapeutic agent	1493:1511	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	7	7	theme	therapeutic	1495:1505	arg1	potential					1464:1472	the potential	1460:1472	the potential of soluble CD52	1460:1488	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	4	8	theme	Box	808:810	arg1	HMGB1					824:828	HMGB1	824:828	HMGB1	824:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	4	8	theme	Box	808:810	arg1	domain					814:819	the antiinflammatory Box A domain	787:819	the antiinflammatory Box A domain of HMGB1	787:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	4	9	theme	anti-HMGB1	764:773	arg1	antibody					775:782	anti-HMGB1 antibody	764:782	anti-HMGB1 antibody	764:782	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	5	10	theme	tyrosine	847:854	arg1	phosphorylation					856:870	tyrosine phosphorylation	847:870	tyrosine phosphorylation of Siglec-10	847:883	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	1	11	theme	T	225:225	arg1	activation					232:241	T cell activation	225:241	T cell activation	225:241	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	0	12	theme	Siglec-10	67:75	arg1	receptor					77:84	the Siglec-10 receptor	63:84	the Siglec-10 receptor	63:84	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	1	13	theme	cell	227:230	arg1	activation					232:241	T cell activation	225:241	T cell activation	225:241	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	2	14	theme	molecular	454:462	arg1	protein					479:485	the damage-associated molecular pattern (DAMP) protein	432:485	the damage-associated molecular pattern (DAMP) protein	432:485	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	14	theme	molecular	454:462	arg1	box					508:510	high-mobility group box 1	488:512	high-mobility group box 1 (HMGB1)	488:520	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	1	15	gly	glycoprotein	171:182	arg1	glycoprotein					171:182	a glycophosphatidylinositol (GPI)-anchored glycoprotein	128:182	a glycophosphatidylinositol (GPI)-anchored glycoprotein	128:182	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	1	15	gly	glycoprotein	171:182	arg1	CD52					122:125	CD52	122:125	CD52	122:125	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	6	16	theme	Siglec-10	1308:1316	arg1	motif					1299:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif	1240:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10	1240:1316	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	2	17	theme	damage-associated	436:452	arg1	protein					479:485	the damage-associated molecular pattern (DAMP) protein	432:485	the damage-associated molecular pattern (DAMP) protein	432:485	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	17	theme	damage-associated	436:452	arg1	box					508:510	high-mobility group box 1	488:512	high-mobility group box 1 (HMGB1)	488:520	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	5	18	theme	T	996:996	arg1	TCR					1013:1015	TCR	1013:1015	TCR	1013:1015	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	5	18	theme	T	996:996	arg1	receptor					1003:1010	the T cell receptor	992:1010	the T cell receptor (TCR)	992:1016	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	2	19	theme	T	404:404	arg1	suppression					411:421	T cell suppression	404:421	T cell suppression	404:421	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	5	20	theme	Siglec-10	875:883	arg1	phosphorylation					856:870	tyrosine phosphorylation	847:870	tyrosine phosphorylation of Siglec-10	847:883	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	6	21	with	recruitment	1217:1227	arg1	TCR					1347:1349	the TCR	1343:1349	the TCR	1343:1349	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	6	22	theme	SHP1	1232:1235	arg1	interaction					1326:1336	its interaction	1322:1336	its interaction with the TCR	1322:1349	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	6	22	theme	SHP1	1232:1235	arg1	recruitment					1217:1227	recruitment	1217:1227	recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10	1217:1316	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	2	23	theme	CD52-Fc	379:385	arg1	binding					368:374	binding	368:374	binding of CD52-Fc to Siglec-10 and T cell suppression	368:421	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	1	24	theme	T	319:319	arg1	cells					321:325	T cells	319:325	T cells	319:325	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	4	25	theme	function	740:747	arg1	Suppression					718:728	Suppression	718:728	Suppression of T cell function	718:747	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	7	26	from	homeostasis	1405:1415	arg1	states					1437:1442	pathophysiologic states	1420:1442	pathophysiologic states	1420:1442	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	6	27	theme	soluble	1025:1031	arg1	CD52					1033:1036	soluble CD52	1025:1036	soluble CD52	1025:1036	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	6	28	theme	inhibitory	1175:1184	arg1	receptor					1196:1203	the inhibitory Siglec-10 receptor	1171:1203	the inhibitory Siglec-10 receptor	1171:1203	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	7	29	theme	pathophysiologic	1420:1435	arg1	states					1437:1442	pathophysiologic states	1420:1442	pathophysiologic states	1420:1442	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	0	30	theme	CD52	0:3	arg1	glycan					5:10	CD52 glycan	0:10	CD52 glycan	0:10	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	3	31	theme	glycan	651:656	arg1	binding					622:628	binding	622:628	binding of the CD52 N-linked glycan	622:656	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	4	32	theme	cell	735:738	arg1	function					740:747	T cell function	733:747	T cell function	733:747	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	7	33	theme	immune-inflammatory	1385:1403	arg1	homeostasis					1405:1415	immune-inflammatory homeostasis	1385:1415	immune-inflammatory homeostasis in pathophysiologic states	1385:1442	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	4	34	theme	T	733:733	arg1	function					740:747	T cell function	733:747	T cell function	733:747	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	0	35	theme	T	105:105	arg1	function					112:119	human T cell function	99:119	human T cell function	99:119	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	7	36	theme	soluble	1477:1483	arg1	CD52					1485:1488	soluble CD52	1477:1488	soluble CD52	1477:1488	This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.
29997173	6	37	theme	intracellular	1244:1256	arg1	motif					1299:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif	1240:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10	1240:1316	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	1	38	theme	-anchored	161:169	arg1	glycoprotein					171:182	a glycophosphatidylinositol (GPI)-anchored glycoprotein	128:182	a glycophosphatidylinositol (GPI)-anchored glycoprotein	128:182	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	1	38	theme	-anchored	161:169	arg1	CD52					122:125	CD52	122:125	CD52	122:125	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	1	39	from	receptor	307:314	arg1	cells					321:325	T cells	319:325	T cells	319:325	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	3	40	theme	CD52	637:640	arg1	glycan					651:656	the CD52 N-linked glycan	633:656	the CD52 N-linked glycan	633:656	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	0	41	theme	human	99:103	arg1	function					112:119	human T cell function	99:119	human T cell function	99:119	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	3	42	theme	Box	573:575	arg1	HMGB1					589:593	HMGB1	589:593	HMGB1	589:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	3	42	theme	Box	573:575	arg1	domain					579:584	the proinflammatory Box B domain	553:584	the proinflammatory Box B domain of HMGB1	553:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	5	43	with	association	954:964	arg1	TCR					1013:1015	TCR	1013:1015	TCR	1013:1015	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	5	43	with	association	954:964	arg1	receptor					1003:1010	the T cell receptor	992:1010	the T cell receptor (TCR)	992:1016	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	5	43	with	association	954:964	arg1	phosphatase					976:986	SHP1 phosphatase	971:986	SHP1 phosphatase	971:986	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	0	44	theme	B	38:38	arg1	box					40:42	the proinflammatory B box	18:42	the proinflammatory B box of HMGB1	18:51	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	3	45	theme	N-linked	642:649	arg1	glycan					651:656	the CD52 N-linked glycan	633:656	the CD52 N-linked glycan	633:656	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	4	46	theme	HMGB1	824:828	arg1	antibody					775:782	anti-HMGB1 antibody	764:782	anti-HMGB1 antibody	764:782	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	4	46	theme	HMGB1	824:828	arg1	domain					814:819	the antiinflammatory Box A domain	787:819	the antiinflammatory Box A domain of HMGB1	787:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	4	46	theme	HMGB1	824:828	arg1	HMGB1					824:828	HMGB1	824:828	HMGB1	824:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	3	47	theme	B	577:577	arg1	HMGB1					589:593	HMGB1	589:593	HMGB1	589:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	3	47	theme	B	577:577	arg1	domain					579:584	the proinflammatory Box B domain	553:584	the proinflammatory Box B domain of HMGB1	553:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	5	48	theme	T	908:908	arg1	cells					910:914	T cells	908:914	T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR)	908:1016	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	6	49	theme	immunosuppressive	1057:1073	arg1	effect					1075:1080	a concerted immunosuppressive effect	1045:1080	a concerted immunosuppressive effect	1045:1080	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	0	50	theme	proinflammatory	22:36	arg1	box					40:42	the proinflammatory B box	18:42	the proinflammatory B box of HMGB1	18:51	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	3	51	theme	sialic	668:673	arg1	acid					675:678	α-2,3 sialic acid	662:678	α-2,3 sialic acid linkage with galactose	662:701	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	0	52	theme	cell	107:110	arg1	function					112:119	human T cell function	99:119	human T cell function	99:119	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	5	53	theme	SHP1	971:974	arg1	phosphatase					976:986	SHP1 phosphatase	971:986	SHP1 phosphatase	971:986	CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR).
29997173	3	54	theme	α-2,3	662:666	arg1	acid					675:678	α-2,3 sialic acid	662:678	α-2,3 sialic acid linkage with galactose	662:701	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	3	55	theme	acid	675:678	arg1	linkage					680:686	α-2,3 sialic acid linkage	662:686	α-2,3 sialic acid linkage with galactose	662:701	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	6	56	theme	Siglec-10	1186:1194	arg1	receptor					1196:1203	the inhibitory Siglec-10 receptor	1171:1203	the inhibitory Siglec-10 receptor	1171:1203	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	3	57	theme	proinflammatory	557:571	arg1	HMGB1					589:593	HMGB1	589:593	HMGB1	589:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	3	57	theme	proinflammatory	557:571	arg1	domain					579:584	the proinflammatory Box B domain	553:584	the proinflammatory Box B domain of HMGB1	553:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	4	58	theme	antiinflammatory	791:806	arg1	HMGB1					824:828	HMGB1	824:828	HMGB1	824:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	4	58	theme	antiinflammatory	791:806	arg1	domain					814:819	the antiinflammatory Box A domain	787:819	the antiinflammatory Box A domain of HMGB1	787:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	2	59	theme	DAMP	473:476	arg1	protein					479:485	the damage-associated molecular pattern (DAMP) protein	432:485	the damage-associated molecular pattern (DAMP) protein	432:485	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	59	theme	DAMP	473:476	arg1	box					508:510	high-mobility group box 1	488:512	high-mobility group box 1 (HMGB1)	488:520	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	4	60	theme	A	812:812	arg1	HMGB1					824:828	HMGB1	824:828	HMGB1	824:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	4	60	theme	A	812:812	arg1	domain					814:819	the antiinflammatory Box A domain	787:819	the antiinflammatory Box A domain of HMGB1	787:828	Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1.
29997173	3	61	theme	HMGB1	589:593	arg1	HMGB1					589:593	HMGB1	589:593	HMGB1	589:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	3	61	theme	HMGB1	589:593	arg1	domain					579:584	the proinflammatory Box B domain	553:584	the proinflammatory Box B domain of HMGB1	553:593	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	6	62	theme	Box	1141:1143	arg1	B					1145:1145	its proinflammatory Box B	1121:1145	its proinflammatory Box B	1121:1145	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	1	63	theme	sialic	268:273	arg1	lectin					296:301	sialic acid-binding Ig-like lectin	268:301	sialic acid-binding Ig-like lectin	268:301	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	1	63	theme	sialic	268:273	arg1	Siglec					260:265	the Siglec	256:265	the Siglec (sialic acid-binding Ig-like lectin)	256:302	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	2	64	theme	group	502:506	arg1	protein					479:485	the damage-associated molecular pattern (DAMP) protein	432:485	the damage-associated molecular pattern (DAMP) protein	432:485	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	64	theme	group	502:506	arg1	box					508:510	high-mobility group box 1	488:512	high-mobility group box 1 (HMGB1)	488:520	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	64	theme	group	502:506	arg1	HMGB1					515:519	HMGB1	515:519	HMGB1	515:519	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	65	theme	high-mobility	488:500	arg1	protein					479:485	the damage-associated molecular pattern (DAMP) protein	432:485	the damage-associated molecular pattern (DAMP) protein	432:485	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	65	theme	high-mobility	488:500	arg1	box					508:510	high-mobility group box 1	488:512	high-mobility group box 1 (HMGB1)	488:520	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	65	theme	high-mobility	488:500	arg1	HMGB1					515:519	HMGB1	515:519	HMGB1	515:519	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	6	66	theme	concerted	1047:1055	arg1	effect					1075:1080	a concerted immunosuppressive effect	1045:1080	a concerted immunosuppressive effect	1045:1080	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	3	67	with	linkage	680:686	arg1	galactose					693:701	galactose	693:701	galactose	693:701	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	6	68	theme	inhibitory	1288:1297	arg1	motif					1299:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif	1240:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10	1240:1316	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	6	69	theme	tyrosine-based	1273:1286	arg1	motif					1299:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif	1240:1303	the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10	1240:1316	Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR.
29997173	3	70	link	N-linked	642:649	arg1	glycan					651:656	the CD52 N-linked glycan	633:656	the CD52 N-linked glycan	633:656	CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10.
29997173	0	71	theme	HMGB1	47:51	arg1	box					40:42	the proinflammatory B box	18:42	the proinflammatory B box of HMGB1	18:51	CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.
29997173	1	72	theme	acid-binding	275:286	arg1	lectin					296:301	sialic acid-binding Ig-like lectin	268:301	sialic acid-binding Ig-like lectin	268:301	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	1	72	theme	acid-binding	275:286	arg1	Siglec					260:265	the Siglec	256:265	the Siglec (sialic acid-binding Ig-like lectin)	256:302	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	1	73	theme	soluble	202:208	arg1	form					210:213	a soluble form	200:213	a soluble form	200:213	CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function.
29997173	2	74	theme	pattern	464:470	arg1	protein					479:485	the damage-associated molecular pattern (DAMP) protein	432:485	the damage-associated molecular pattern (DAMP) protein	432:485	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
29997173	2	74	theme	pattern	464:470	arg1	box					508:510	high-mobility group box 1	488:512	high-mobility group box 1 (HMGB1)	488:520	We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1).
31631785	0	0	theme	SARS-CoV	76:83	arg1	virus					114:118	Lassa fever virus	102:118	Lassa fever virus	102:118	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	0	theme	SARS-CoV	76:83	arg1	virus					92:96	Ebola virus	86:96	Ebola virus	86:96	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	0	theme	SARS-CoV	76:83	arg1	glycoproteins					59:71	the envelope glycoproteins	46:71	the envelope glycoproteins of SARS-CoV	46:83	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	7	1	theme	enveloped	1376:1384	arg1	viruses					1390:1396	selected enveloped RNA viruses	1367:1396	selected enveloped RNA viruses	1367:1396	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	6	2	theme	RNA	1248:1250	arg1	viruses					1252:1258	these RNA viruses	1242:1258	these RNA viruses	1242:1258	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	4	3	theme	envelope	849:856	arg1	glycoproteins					858:870	these viral envelope glycoproteins	837:870	these viral envelope glycoproteins	837:870	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	7	4	theme	novel	1307:1311	arg1	ISG					1323:1325	a novel antiviral ISG	1305:1325	a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses	1305:1535	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	7	4	theme	novel	1307:1311	arg1	GILT					1297:1300	GILT	1297:1300	GILT	1297:1300	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	7	5	theme	selected	1367:1374	arg1	viruses					1390:1396	selected enveloped RNA viruses	1367:1396	selected enveloped RNA viruses	1367:1396	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	4	6	gly	glycoproteins	858:870	arg1	glycoproteins					858:870	these viral envelope glycoproteins	837:870	these viral envelope glycoproteins	837:870	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	0	7	theme	Ebola	86:90	arg1	virus					92:96	Ebola virus	86:96	Ebola virus	86:96	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	7	theme	Ebola	86:90	arg1	glycoproteins					59:71	the envelope glycoproteins	46:71	the envelope glycoproteins of SARS-CoV	46:83	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	7	8	theme	cathepsin	1429:1437	arg1	L					1439:1439	cathepsin L metabolism and function	1429:1463	L	1439:1439	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	7	9	theme	antiviral	1313:1321	arg1	ISG					1323:1325	a novel antiviral ISG	1305:1325	a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses	1305:1535	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	7	9	theme	antiviral	1313:1321	arg1	GILT					1297:1300	GILT	1297:1300	GILT	1297:1300	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	6	10	theme	GILT	1144:1147	arg1	expression					1149:1158	GILT expression	1144:1158	GILT expression	1144:1158	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	5	11	theme	reductase	920:928	arg1	activity					930:937	the thiol reductase activity	910:937	the thiol reductase activity	910:937	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	5	12	theme	thiol	914:918	arg1	activity					930:937	the thiol reductase activity	910:937	the thiol reductase activity	910:937	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	1	13	theme	distinct	233:240	arg1	steps					242:246	distinct steps	233:246	distinct steps of viral replication	233:267	Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication.
31631785	7	14	theme	viruses	1390:1396	arg1	entry					1358:1362	the entry	1354:1362	the entry of selected enveloped RNA viruses in lysosomes	1354:1409	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	0	15	gly	glycoproteins	59:71	arg1	virus					114:118	Lassa fever virus	102:118	Lassa fever virus	102:118	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	15	gly	glycoproteins	59:71	arg1	virus					92:96	Ebola virus	86:96	Ebola virus	86:96	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	15	gly	glycoproteins	59:71	arg1	glycoproteins					59:71	the envelope glycoproteins	46:71	the envelope glycoproteins of SARS-CoV	46:83	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	4	16	theme	coronavirus	715:725	arg1	glycoproteins					693:705	envelope glycoproteins	684:705	envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV)	684:785	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	3	17	theme	lung	518:521	arg1	cells					534:538	lung epithelial cells	518:538	lung epithelial cells	518:538	Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon.
31631785	5	18	theme	viral	1095:1099	arg1	entry					1101:1105	viral entry	1095:1105	viral entry	1095:1105	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	3	19	theme	epithelial	523:532	arg1	cells					534:538	lung epithelial cells	518:538	lung epithelial cells	518:538	Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon.
31631785	1	20	theme	viral	148:152	arg1	infections					154:163	viral infections	148:163	viral infections	148:163	Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication.
31631785	2	21	theme	RNA	433:435	arg1	viruses					437:443	selected enveloped RNA viruses	414:443	selected enveloped RNA viruses	414:443	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	5	22	theme	entry	1101:1105	arg1	restriction					1080:1090	GILT restriction	1075:1090	GILT restriction of viral entry	1075:1105	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	6	23	theme	viruses	1252:1258	arg1	entry					1233:1237	the entry	1229:1237	the entry of these RNA viruses in lysosomes	1229:1271	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	2	24	theme	lysosome-associated	355:373	arg1	ISG					375:377	a lysosome-associated ISG	353:377	a lysosome-associated ISG	353:377	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	24	theme	lysosome-associated	355:373	arg1	reductase					335:343	gamma-interferon-inducible lysosomal thiol reductase	292:343	gamma-interferon-inducible lysosomal thiol reductase (GILT)	292:350	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	25	theme	enveloped	423:431	arg1	viruses					437:443	selected enveloped RNA viruses	414:443	selected enveloped RNA viruses	414:443	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	7	26	theme	RNA	1386:1388	arg1	viruses					1390:1396	selected enveloped RNA viruses	1367:1396	selected enveloped RNA viruses	1367:1396	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	4	27	theme	GILT	801:804	arg1	depletion					788:796	depletion	788:796	depletion of GILT	788:804	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	2	28	theme	selected	414:421	arg1	viruses					437:443	selected enveloped RNA viruses	414:443	selected enveloped RNA viruses	414:443	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	1	29	theme	viral	251:255	arg1	replication					257:267	viral replication	251:267	viral replication	251:267	Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication.
31631785	0	30	theme	fever	108:112	arg1	virus					114:118	Lassa fever virus	102:118	Lassa fever virus	102:118	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	30	theme	fever	108:112	arg1	glycoproteins					59:71	the envelope glycoproteins	46:71	the envelope glycoproteins of SARS-CoV	46:83	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	6	31	theme	cathepsin	1194:1202	arg1	L					1204:1204	cathepsin L	1194:1204	cathepsin L	1194:1204	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	4	32	theme	Ebola	739:743	arg1	coronavirus					715:725	SARS coronavirus	710:725	SARS coronavirus (SARS-CoV)	710:736	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	32	theme	Ebola	739:743	arg1	EBOV					752:755	EBOV	752:755	EBOV	752:755	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	32	theme	Ebola	739:743	arg1	virus					745:749	Ebola virus	739:749	Ebola virus (EBOV)	739:756	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	5	33	link	N-linked	956:963	arg1	glycosylation					965:977	the N-linked glycosylation	952:977	the N-linked glycosylation	952:977	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	1	34	theme	replication	257:267	arg1	steps					242:246	distinct steps	233:246	distinct steps of viral replication	233:267	Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication.
31631785	0	35	theme	Lassa	102:106	arg1	virus					114:118	Lassa fever virus	102:118	Lassa fever virus	102:118	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	35	theme	Lassa	102:106	arg1	glycoproteins					59:71	the envelope glycoproteins	46:71	the envelope glycoproteins of SARS-CoV	46:83	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	4	36	theme	envelope	684:691	arg1	glycoproteins					693:705	envelope glycoproteins	684:705	envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV)	684:785	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	2	37	theme	infectious	394:403	arg1	entry					405:409	the infectious entry	390:409	the infectious entry of selected enveloped RNA viruses	390:443	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	6	38	dep	level	1172:1176	arg1	the					1168:1170	the	1168:1170	the	1168:1170	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	0	39	theme	cellular	19:26	arg1	entry					28:32	the cellular entry	15:32	the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus	15:118	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	1	40	theme	IFN-stimulated	191:204	arg1	ISGs					213:216	ISGs	213:216	ISGs	213:216	Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication.
31631785	1	40	theme	IFN-stimulated	191:204	arg1	genes					206:210	IFN-stimulated genes	191:210	IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication	191:267	Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication.
31631785	4	41	theme	viral	843:847	arg1	glycoproteins					858:870	these viral envelope glycoproteins	837:870	these viral envelope glycoproteins	837:870	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	5	42	theme	GILT	1075:1078	arg1	restriction					1080:1090	GILT restriction	1075:1090	GILT restriction of viral entry	1075:1105	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	6	43	theme	L	1204:1204	arg1	activity					1182:1189	activity	1182:1189	activity	1182:1189	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	6	43	theme	L	1204:1204	arg1	level					1172:1176	level	1172:1176	level	1172:1176	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	4	44	theme	SARS	710:713	arg1	SARS-CoV					728:735	SARS-CoV	728:735	SARS-CoV	728:735	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	44	theme	SARS	710:713	arg1	virus					774:778	Lassa fever virus	762:778	Lassa fever virus (LASV)	762:785	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	44	theme	SARS	710:713	arg1	coronavirus					715:725	SARS coronavirus	710:725	SARS coronavirus (SARS-CoV)	710:736	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	44	theme	SARS	710:713	arg1	virus					745:749	Ebola virus	739:749	Ebola virus (EBOV)	739:756	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	2	45	theme	viruses	437:443	arg1	entry					405:409	the infectious entry	390:409	the infectious entry of selected enveloped RNA viruses	390:443	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	5	46	theme	essential	1013:1021	arg1	modification					1000:1011	a posttranslational modification	980:1011	a posttranslational modification essential for its lysosomal localization	980:1052	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	5	46	theme	essential	1013:1021	arg1	mutations					886:894	mutations	886:894	mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation	886:977	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	2	47	theme	thiol	329:333	arg1	ISG					375:377	a lysosome-associated ISG	353:377	a lysosome-associated ISG	353:377	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	47	theme	thiol	329:333	arg1	GILT					346:349	GILT	346:349	GILT	346:349	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	47	theme	thiol	329:333	arg1	reductase					335:343	gamma-interferon-inducible lysosomal thiol reductase	292:343	gamma-interferon-inducible lysosomal thiol reductase (GILT)	292:350	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	4	48	theme	fever	768:772	arg1	LASV					781:784	LASV	781:784	LASV	781:784	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	48	theme	fever	768:772	arg1	virus					774:778	Lassa fever virus	762:778	Lassa fever virus (LASV)	762:785	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	48	theme	fever	768:772	arg1	coronavirus					715:725	SARS coronavirus	710:725	SARS coronavirus (SARS-CoV)	710:736	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	6	49	theme	expression	1149:1158	arg1	induction					1131:1139	the induction	1127:1139	the induction of GILT expression	1127:1158	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	4	50	theme	Lassa	762:766	arg1	LASV					781:784	LASV	781:784	LASV	781:784	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	50	theme	Lassa	762:766	arg1	virus					774:778	Lassa fever virus	762:778	Lassa fever virus (LASV)	762:785	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	4	50	theme	Lassa	762:766	arg1	coronavirus					715:725	SARS coronavirus	710:725	SARS coronavirus (SARS-CoV)	710:736	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	5	51	theme	posttranslational	982:998	arg1	modification					1000:1011	a posttranslational modification	980:1011	a posttranslational modification essential for its lysosomal localization	980:1052	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	5	51	theme	posttranslational	982:998	arg1	mutations					886:894	mutations	886:894	mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation	886:977	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	2	52	theme	lysosomal	319:327	arg1	ISG					375:377	a lysosome-associated ISG	353:377	a lysosome-associated ISG	353:377	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	52	theme	lysosomal	319:327	arg1	GILT					346:349	GILT	346:349	GILT	346:349	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	52	theme	lysosomal	319:327	arg1	reductase					335:343	gamma-interferon-inducible lysosomal thiol reductase	292:343	gamma-interferon-inducible lysosomal thiol reductase (GILT)	292:350	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	1	53	theme	genes	206:210	arg1	expression					177:186	expression	177:186	expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication	177:267	Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication.
31631785	4	54	gly	glycoproteins	693:705	arg1	glycoproteins					693:705	envelope glycoproteins	684:705	envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV)	684:785	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	5	55	theme	lysosomal	1031:1039	arg1	localization					1041:1052	its lysosomal localization	1027:1052	its lysosomal localization	1027:1052	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	5	56	theme	N-linked	956:963	arg1	glycosylation					965:977	the N-linked glycosylation	952:977	the N-linked glycosylation	952:977	Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry.
31631785	7	57	theme	immune	1488:1493	arg1	control					1495:1501	control	1495:1501	control	1495:1501	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	2	58	theme	gamma-interferon-inducible	292:317	arg1	ISG					375:377	a lysosome-associated ISG	353:377	a lysosome-associated ISG	353:377	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	58	theme	gamma-interferon-inducible	292:317	arg1	GILT					346:349	GILT	346:349	GILT	346:349	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	2	58	theme	gamma-interferon-inducible	292:317	arg1	reductase					335:343	gamma-interferon-inducible lysosomal thiol reductase	292:343	gamma-interferon-inducible lysosomal thiol reductase (GILT)	292:350	We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses.
31631785	7	59	from	entry	1358:1362	arg1	lysosomes					1401:1409	lysosomes	1401:1409	lysosomes	1401:1409	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	6	60	from	entry	1233:1237	arg1	lysosomes					1263:1271	lysosomes	1263:1271	lysosomes	1263:1271	We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes.
31631785	7	61	theme	function	1456:1463	arg1	disruption					1415:1424	disruption	1415:1424	disruption of cathepsin L metabolism and function	1415:1463	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	4	62	theme	GILT	647:650	arg1	overexpression					629:642	overexpression	629:642	overexpression of GILT	629:650	While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins.
31631785	0	63	theme	envelope	50:57	arg1	virus					114:118	Lassa fever virus	102:118	Lassa fever virus	102:118	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	63	theme	envelope	50:57	arg1	virus					92:96	Ebola virus	86:96	Ebola virus	86:96	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	0	63	theme	envelope	50:57	arg1	glycoproteins					59:71	the envelope glycoproteins	46:71	the envelope glycoproteins of SARS-CoV	46:83	GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus.
31631785	7	64	theme	L	1439:1439	arg1	disruption					1415:1424	disruption	1415:1424	disruption of cathepsin L metabolism and function	1415:1463	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	3	65	theme	type	603:606	arg1	interferon					611:620	type II interferon	603:620	type II interferon	603:620	Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon.
31631785	7	66	dep	L	1439:1439	arg1	metabolism					1441:1450	metabolism	1441:1450	metabolism	1441:1450	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	7	67	theme	viruses	1529:1535	arg1	pathogenesis					1507:1518	pathogenesis	1507:1518	pathogenesis	1507:1518	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
31631785	7	67	theme	viruses	1529:1535	arg1	control					1495:1501	control	1495:1501	control	1495:1501	Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
30021839	8	0	theme	component	1516:1524	arg1	ERdj5					1526:1530	the ERAD component ERdj5	1507:1530	the ERAD component ERdj5	1507:1530	We also determined that both IDRs are required for binding to the ERAD component ERdj5 as an interaction with ERdj5 was not observed with the MLD alone.
30021839	6	1	contain	had	1190:1192	arg2	properties					1218:1227	thiol-dependent binding properties	1194:1227	thiol-dependent binding properties	1194:1227	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	6	1	contain	had	1190:1192	arg1	construct					1155:1163	a protein construct	1145:1163	a protein construct comprising the EDEM1 MLD	1145:1188	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	1	2	link	N-linked	284:291	arg1	glycans					293:299	N-linked glycans	284:299	N-linked glycans on misfolded proteins	284:321	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	3	theme	degradation-enhancing	148:168	arg1	factor					236:241	a protein quality control factor	210:241	a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD)	210:363	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	3	theme	degradation-enhancing	148:168	arg1	EDEM1					200:204	EDEM1	200:204	EDEM1	200:204	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	3	theme	degradation-enhancing	148:168	arg1	protein					191:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein	121:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1)	121:205	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	0	4	theme	redox-sensitive	64:78	arg1	manner					80:85	a redox-sensitive manner	62:85	a redox-sensitive manner	62:85	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	5	5	theme	redox-sensitive	1101:1115	arg1	binding					1117:1123	the observed redox-sensitive binding	1088:1123	the observed redox-sensitive binding by EDEM1	1088:1132	About four reactive thiols on EDEM1 were identified and were not directly responsible for the observed redox-sensitive binding by EDEM1.
30021839	4	6	theme	thiol-dependent	851:865	arg1	interaction					867:877	the thiol-dependent interaction	847:877	the thiol-dependent interaction	847:877	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	1	7	theme	α-mannosidase-like	170:187	arg1	factor					236:241	a protein quality control factor	210:241	a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD)	210:363	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	7	theme	α-mannosidase-like	170:187	arg1	EDEM1					200:204	EDEM1	200:204	EDEM1	200:204	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	7	theme	α-mannosidase-like	170:187	arg1	protein					191:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein	121:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1)	121:205	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	2	8	theme	binding	510:516	arg1	landscape					518:526	a more complex binding landscape	495:526	a more complex binding landscape for EDEM1	495:536	However, recent studies have demonstrated that EDEM1 binds to some misfolded proteins in a glycan-independent manner, suggesting a more complex binding landscape for EDEM1.
30021839	9	9	theme	binding	1659:1665	arg1	modalities					1667:1676	different binding modalities	1649:1676	different binding modalities	1649:1676	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	7	10	from	terminus	1370:1377	arg1	located					1353:1359	located	1353:1359	located	1353:1359	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	3	11	theme	stringent	800:808	arg1	conditions					820:829	stringent detergent conditions	800:829	stringent detergent conditions	800:829	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	7	12	theme	additional	1304:1313	arg1	IDR					1348:1350	IDR	1348:1350	IDR	1348:1350	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	7	12	theme	additional	1304:1313	arg1	region					1340:1345	an additional intrinsically disordered region	1301:1345	an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1	1301:1386	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	0	13	from	proteins	50:57	arg1	manner					80:85	a redox-sensitive manner	62:85	a redox-sensitive manner	62:85	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	6	14	theme	binding	1210:1216	arg1	properties					1218:1227	thiol-dependent binding properties	1194:1227	thiol-dependent binding properties	1194:1227	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	3	15	theme	detergent	810:818	arg1	conditions					820:829	stringent detergent conditions	800:829	stringent detergent conditions	800:829	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	4	16	theme	client-binding	971:984	arg1	properties					986:995	bipartite client-binding properties	961:995	bipartite client-binding properties	961:995	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	3	17	theme	single	735:740	arg1	residue					746:752	the single Cys residue	731:752	the single Cys residue	731:752	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	1	18	from	glycans	293:299	arg1	proteins					314:321	misfolded proteins	304:321	misfolded proteins	304:321	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	3	19	dep	clients	691:697	arg1	NHK					705:707	NHK	705:707	NHK	705:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	19	dep	clients	691:697	arg1	Z					699:699	Z	699:699	Z	699:699	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	19	dep	clients	691:697	arg1	clients					691:697	EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients	621:697	EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK	621:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	7	20	theme	C	1368:1368	arg1	terminus					1370:1377	the C terminus	1364:1377	the C terminus of EDEM1	1364:1386	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	0	21	theme	catalytic	101:109	arg1	activity					111:118	catalytic activity	101:118	catalytic activity	101:118	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	3	22	from	residue	746:752	arg1	Cys256					764:769	Cys256	764:769	Cys256	764:769	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	22	from	residue	746:752	arg1	Z/NHK					757:761	Z/NHK	757:761	Z/NHK (Cys256)	757:770	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	9	23	theme	ERAD	1695:1698	arg1	clients					1700:1706	ERAD clients	1695:1706	ERAD clients	1695:1706	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	5	24	from	thiols	1018:1023	arg1	EDEM1					1028:1032	EDEM1	1028:1032	EDEM1	1028:1032	About four reactive thiols on EDEM1 were identified and were not directly responsible for the observed redox-sensitive binding by EDEM1.
30021839	6	25	theme	EDEM1	1180:1184	arg1	MLD					1186:1188	the EDEM1 MLD	1176:1188	the EDEM1 MLD	1176:1188	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	2	26	theme	recent	375:380	arg1	studies					382:388	recent studies	375:388	recent studies	375:388	However, recent studies have demonstrated that EDEM1 binds to some misfolded proteins in a glycan-independent manner, suggesting a more complex binding landscape for EDEM1.
30021839	2	27	theme	misfolded	433:441	arg1	proteins					443:450	some misfolded proteins	428:450	some misfolded proteins	428:450	However, recent studies have demonstrated that EDEM1 binds to some misfolded proteins in a glycan-independent manner, suggesting a more complex binding landscape for EDEM1.
30021839	1	28	theme	N-linked	284:291	arg1	glycans					293:299	N-linked glycans	284:299	N-linked glycans on misfolded proteins	284:321	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	9	29	theme	ER	1712:1713	arg1	control					1723:1729	ER quality control	1712:1729	ER quality control (ERQC) machinery partners	1712:1755	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	9	29	theme	ER	1712:1713	arg1	ERQC					1732:1735	ERQC	1732:1735	ERQC	1732:1735	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	6	30	theme	glycan-trimming	1251:1265	arg1	activities					1267:1276	its active glycan-trimming activities	1240:1276	its active glycan-trimming activities	1240:1276	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	7	31	theme	N-terminal	1429:1438	arg1	IDR					1440:1442	its previously identified N-terminal IDR	1403:1442	its previously identified N-terminal IDR	1403:1442	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	0	32	theme	mannosidase-like	8:23	arg1	domain					25:30	EDEM1's mannosidase-like domain	0:30	EDEM1's mannosidase-like domain	0:30	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	3	33	theme	Cys	742:744	arg1	residue					746:752	the single Cys residue	731:752	the single Cys residue	731:752	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	4	34	theme	interactions	919:930	arg1	presence					884:891	the presence	880:891	the presence of weaker protein-protein interactions	880:930	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	3	35	theme	protein	664:670	arg1	ERAD					685:688	ERAD	685:688	ERAD	685:688	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	35	theme	protein	664:670	arg1	degradation					672:682	the α1-antitrypsin ER-associated protein degradation	631:682	the α1-antitrypsin ER-associated protein degradation (ERAD)	631:689	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	7	36	theme	located	1353:1359	arg1	IDR					1348:1350	IDR	1348:1350	IDR	1348:1350	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	7	36	theme	located	1353:1359	arg1	region					1340:1345	an additional intrinsically disordered region	1301:1345	an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1	1301:1386	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	0	37	theme	ERAD	38:41	arg1	proteins					50:57	ERAD client proteins	38:57	ERAD client proteins in a redox-sensitive manner	38:85	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	6	38	theme	protein	1147:1153	arg1	construct					1155:1163	a protein construct	1145:1163	a protein construct comprising the EDEM1 MLD	1145:1188	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	9	39	theme	control	1723:1729	arg1	partners					1748:1755	ER quality control (ERQC) machinery partners	1712:1755	ER quality control (ERQC) machinery partners	1712:1755	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	3	40	theme	degradation	672:682	arg1	NHK					705:707	NHK	705:707	NHK	705:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	40	theme	degradation	672:682	arg1	Z					699:699	Z	699:699	Z	699:699	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	40	theme	degradation	672:682	arg1	clients					691:697	EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients	621:697	EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK	621:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	41	theme	substrate	591:599	arg1	interaction					601:611	a thiol-dependent substrate interaction	573:611	a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK	573:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	9	42	dep	homologues	1811:1820	arg1	homologues					1811:1820	its homologues	1807:1820	its homologues EDEM2 and EDEM3	1807:1836	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	9	42	dep	homologues	1811:1820	arg1	EDEM3					1832:1836	EDEM3	1832:1836	EDEM3	1832:1836	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	9	42	dep	homologues	1811:1820	arg1	EDEM2					1822:1826	EDEM2	1822:1826	EDEM2	1822:1826	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	1	43	theme	misfolded	304:312	arg1	proteins					314:321	misfolded proteins	304:321	misfolded proteins	304:321	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	3	44	theme	α1-antitrypsin	635:648	arg1	ERAD					685:688	ERAD	685:688	ERAD	685:688	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	44	theme	α1-antitrypsin	635:648	arg1	degradation					672:682	the α1-antitrypsin ER-associated protein degradation	631:682	the α1-antitrypsin ER-associated protein degradation (ERAD)	631:689	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	7	45	theme	identified	1418:1427	arg1	IDR					1440:1442	its previously identified N-terminal IDR	1403:1442	its previously identified N-terminal IDR	1403:1442	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	1	46	theme	protein	212:218	arg1	factor					236:241	a protein quality control factor	210:241	a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD)	210:363	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	46	theme	protein	212:218	arg1	protein					191:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein	121:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1)	121:205	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	2	47	theme	glycan-independent	457:474	arg1	manner					476:481	a glycan-independent manner	455:481	a glycan-independent manner	455:481	However, recent studies have demonstrated that EDEM1 binds to some misfolded proteins in a glycan-independent manner, suggesting a more complex binding landscape for EDEM1.
30021839	3	48	theme	ER-associated	650:662	arg1	ERAD					685:688	ERAD	685:688	ERAD	685:688	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	48	theme	ER-associated	650:662	arg1	degradation					672:682	the α1-antitrypsin ER-associated protein degradation	631:682	the α1-antitrypsin ER-associated protein degradation (ERAD)	631:689	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	9	49	theme	machinery	1738:1746	arg1	partners					1748:1755	ER quality control (ERQC) machinery partners	1712:1755	ER quality control (ERQC) machinery partners	1712:1755	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	7	50	theme	disordered	1329:1338	arg1	IDR					1348:1350	IDR	1348:1350	IDR	1348:1350	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	7	50	theme	disordered	1329:1338	arg1	region					1340:1345	an additional intrinsically disordered region	1301:1345	an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1	1301:1386	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	0	51	theme	client	43:48	arg1	proteins					50:57	ERAD client proteins	38:57	ERAD client proteins in a redox-sensitive manner	38:85	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	3	52	theme	thiol-dependent	575:589	arg1	interaction					601:611	a thiol-dependent substrate interaction	573:611	a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK	573:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	1	53	theme	Endoplasmic	121:131	arg1	reticulum					133:141	Endoplasmic reticulum	121:141	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1)	121:205	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	53	theme	Endoplasmic	121:131	arg1	ER					144:145	ER	144:145	ER	144:145	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	7	54	theme	EDEM1	1382:1386	arg1	terminus					1370:1377	the C terminus	1364:1377	the C terminus of EDEM1	1364:1386	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	4	55	theme	protein-protein	903:917	arg1	interactions					919:930	weaker protein-protein interactions	896:930	weaker protein-protein interactions	896:930	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	6	56	theme	active	1244:1249	arg1	activities					1267:1276	its active glycan-trimming activities	1240:1276	its active glycan-trimming activities	1240:1276	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	5	57	theme	reactive	1009:1016	arg1	thiols					1018:1023	About four reactive thiols	998:1023	About four reactive thiols on EDEM1	998:1032	About four reactive thiols on EDEM1 were identified and were not directly responsible for the observed redox-sensitive binding by EDEM1.
30021839	0	58	contain	possesses	91:99	arg2	activity					111:118	catalytic activity	101:118	catalytic activity	101:118	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	0	58	contain	possesses	91:99	arg1	domain					25:30	EDEM1's mannosidase-like domain	0:30	EDEM1's mannosidase-like domain	0:30	EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity.
30021839	1	59	theme	reticulum	133:141	arg1	factor					236:241	a protein quality control factor	210:241	a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD)	210:363	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	59	theme	reticulum	133:141	arg1	EDEM1					200:204	EDEM1	200:204	EDEM1	200:204	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	59	theme	reticulum	133:141	arg1	protein					191:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein	121:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1)	121:205	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	60	theme	quality	220:226	arg1	factor					236:241	a protein quality control factor	210:241	a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD)	210:363	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	60	theme	quality	220:226	arg1	protein					191:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein	121:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1)	121:205	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	4	61	theme	weaker	896:901	arg1	interactions					919:930	weaker protein-protein interactions	896:930	weaker protein-protein interactions	896:930	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	8	62	theme	ERAD	1511:1514	arg1	ERdj5					1526:1530	the ERAD component ERdj5	1507:1530	the ERAD component ERdj5	1507:1530	We also determined that both IDRs are required for binding to the ERAD component ERdj5 as an interaction with ERdj5 was not observed with the MLD alone.
30021839	5	63	theme	observed	1092:1099	arg1	binding					1117:1123	the observed redox-sensitive binding	1088:1123	the observed redox-sensitive binding by EDEM1	1088:1132	About four reactive thiols on EDEM1 were identified and were not directly responsible for the observed redox-sensitive binding by EDEM1.
30021839	7	64	dep	IDR	1440:1442	arg1	addition					1391:1398	addition	1391:1398	addition	1391:1398	Lastly, we identified an additional intrinsically disordered region (IDR) located at the C terminus of EDEM1 in addition to its previously identified N-terminal IDR.
30021839	1	65	theme	control	228:234	arg1	factor					236:241	a protein quality control factor	210:241	a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD)	210:363	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	65	theme	control	228:234	arg1	protein					191:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein	121:197	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1)	121:205	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	2	66	theme	complex	502:508	arg1	landscape					518:526	a more complex binding landscape	495:526	a more complex binding landscape for EDEM1	495:536	However, recent studies have demonstrated that EDEM1 binds to some misfolded proteins in a glycan-independent manner, suggesting a more complex binding landscape for EDEM1.
30021839	8	67	with	interaction	1538:1548	arg1	ERdj5					1555:1559	ERdj5	1555:1559	ERdj5	1555:1559	We also determined that both IDRs are required for binding to the ERAD component ERdj5 as an interaction with ERdj5 was not observed with the MLD alone.
30021839	6	68	theme	thiol-dependent	1194:1208	arg1	properties					1218:1227	thiol-dependent binding properties	1194:1227	thiol-dependent binding properties	1194:1227	Moreover, a protein construct comprising the EDEM1 MLD had thiol-dependent binding properties along with its active glycan-trimming activities.
30021839	4	69	theme	properties	986:995	arg1	suggestive					947:956	suggestive	947:956	suggestive	947:956	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	1	70	theme	mannosidase-like	335:350	arg1	MLD					360:362	MLD	360:362	MLD	360:362	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	1	70	theme	mannosidase-like	335:350	arg1	domain					352:357	its mannosidase-like domain	331:357	its mannosidase-like domain (MLD)	331:363	Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is a protein quality control factor that was initially proposed to recognize N-linked glycans on misfolded proteins through its mannosidase-like domain (MLD).
30021839	3	71	theme	EDEM1	621:625	arg1	NHK					705:707	NHK	705:707	NHK	705:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	71	theme	EDEM1	621:625	arg1	Z					699:699	Z	699:699	Z	699:699	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	3	71	theme	EDEM1	621:625	arg1	clients					691:697	EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients	621:697	EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK	621:707	In this study, we have identified a thiol-dependent substrate interaction between EDEM1 and the α1-antitrypsin ER-associated protein degradation (ERAD) clients Z and NHK, specifically through the single Cys residue on Z/NHK (Cys256), required for binding under stringent detergent conditions.
30021839	4	72	dep	interaction	867:877	arg1	addition					835:842	addition	835:842	addition	835:842	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	4	73	theme	bipartite	961:969	arg1	properties					986:995	bipartite client-binding properties	961:995	bipartite client-binding properties	961:995	In addition to the thiol-dependent interaction, the presence of weaker protein-protein interactions was confirmed, suggestive of bipartite client-binding properties.
30021839	9	74	theme	quality	1715:1721	arg1	control					1723:1729	ER quality control	1712:1729	ER quality control (ERQC) machinery partners	1712:1755	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	9	74	theme	quality	1715:1721	arg1	ERQC					1732:1735	ERQC	1732:1735	ERQC	1732:1735	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
30021839	9	75	theme	different	1649:1657	arg1	modalities					1667:1676	different binding modalities	1649:1676	different binding modalities	1649:1676	Together, our findings indicate that EDEM1 employs different binding modalities to interact with ERAD clients and ER quality control (ERQC) machinery partners and that some of these properties are shared with its homologues EDEM2 and EDEM3.
28931878	0	0	theme	rheumatoid	68:77	arg1	arthritis					79:87	rheumatoid arthritis	68:87	rheumatoid arthritis	68:87	A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.
28931878	5	1	theme	rheumatoid	634:643	arg1	arthritis					645:653	rheumatoid arthritis	634:653	rheumatoid arthritis (RA)	634:658	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	1	theme	rheumatoid	634:643	arg1	RA					656:657	RA	656:657	RA	656:657	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	4	2	theme	monitoring	489:498	arg1	method					500:505	multiple reaction monitoring method	471:505	multiple reaction monitoring method	471:505	Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans.
28931878	6	3	theme	therapeutics.Post-translational	1081:1111	arg1	modifications					1113:1125	antibody therapeutics.Post-translational modifications	1072:1125	antibody therapeutics.Post-translational modifications	1072:1125	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	6	4	theme	antibody	1138:1145	arg1	function					1147:1154	antibody function	1138:1154	antibody function in health and disease	1138:1176	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	6	5	theme	autoimmune	981:990	arg1	diseases					1007:1014	other autoimmune and infectious diseases	975:1014	other autoimmune and infectious diseases	975:1014	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	4	6	theme	reaction	480:487	arg1	method					500:505	multiple reaction monitoring method	471:505	multiple reaction monitoring method	471:505	Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans.
28931878	6	7	theme	variants	1205:1212	arg1	identification					1183:1196	identification	1183:1196	identification of all variants	1183:1212	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	6	8	theme	other	975:979	arg1	diseases					1007:1014	other autoimmune and infectious diseases	975:1014	other autoimmune and infectious diseases	975:1014	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	5	9	theme	N-glycan	706:713	arg1	biomarkers					715:724	N-glycan biomarkers	706:724	N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients	706:903	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	1	10	theme	low-abundance	248:260	arg1	species					262:268	low-abundance species	248:268	low-abundance species	248:268	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	5	11	with	patients	620:627	arg1	arthritis					645:653	rheumatoid arthritis	634:653	rheumatoid arthritis (RA)	634:658	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	11	with	patients	620:627	arg1	RA					656:657	RA	656:657	RA	656:657	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	12	theme	patients	805:812	arg1	classification					734:747	the classification	730:747	the classification of both rheumatoid factor (RF)-positive and negative RA patients	730:812	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	12	theme	patients	805:812	arg1	antibodies					853:862	anti-citrullinated protein antibodies	826:862	anti-citrullinated protein antibodies	826:862	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	3	13	theme	acetylated	435:444	arg1	N-glycans					446:454	20 sulfated and 4 acetylated N-glycans	417:454	20 sulfated and 4 acetylated N-glycans on IgGs	417:462	We discover 20 sulfated and 4 acetylated N-glycans on IgGs.
28931878	5	14	dep	-positive	870:878	arg1	classification					734:747	the classification	730:747	the classification of both rheumatoid factor (RF)-positive and negative RA patients	730:812	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	14	dep	-positive	870:878	arg1	antibodies					853:862	anti-citrullinated protein antibodies	826:862	anti-citrullinated protein antibodies	826:862	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	15	theme	anti-citrullinated	826:843	arg1	antibodies					853:862	anti-citrullinated protein antibodies	826:862	anti-citrullinated protein antibodies	826:862	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	6	16	theme	antibody	1072:1079	arg1	modifications					1113:1125	antibody therapeutics.Post-translational modifications	1072:1125	antibody therapeutics.Post-translational modifications	1072:1125	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	5	17	theme	rheumatoid	757:766	arg1	RF					776:777	RF	776:777	RF	776:777	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	17	theme	rheumatoid	757:766	arg1	factor					768:773	rheumatoid factor	757:773	rheumatoid factor (RF)	757:778	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	3	18	from	N-glycans	446:454	arg1	IgGs					459:462	IgGs	459:462	IgGs	459:462	We discover 20 sulfated and 4 acetylated N-glycans on IgGs.
28931878	6	19	dep	glycoforms	1057:1066	arg1	affect					1131:1136	affect	1131:1136	can affect antibody function in health and disease	1127:1176	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	6	19	dep	glycoforms	1057:1066	arg1	difficult					1217:1225	difficult	1217:1225	difficult	1217:1225	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	6	20	theme	glycoforms	1057:1066	arg1	exploration					1032:1042	the exploration	1028:1042	the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies	1028:1253	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	2	21	theme	human	355:359	arg1	IgGs					361:364	human IgGs	355:364	human IgGs using a specialized microfluidic chip	355:402	Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip.
28931878	5	22	theme	-positive	779:787	arg1	patients					805:812	both rheumatoid factor (RF)-positive and negative RA patients	752:812	both rheumatoid factor (RF)-positive and negative RA patients	752:812	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	2	23	from	species	344:350	arg1	IgGs					361:364	human IgGs	355:364	human IgGs using a specialized microfluidic chip	355:402	Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip.
28931878	5	24	theme	protein	845:851	arg1	antibodies					853:862	anti-citrullinated protein antibodies	826:862	anti-citrullinated protein antibodies	826:862	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	6	25	theme	N-glycosylation-associated	933:958	arg1	biomarkers					960:969	N-glycosylation-associated biomarkers	933:969	N-glycosylation-associated biomarkers for other autoimmune and infectious diseases	933:1014	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	1	26	theme	N-linked	90:97	arg1	glycans					99:105	N-linked glycans	90:105	N-linked glycans on immunoglobulin G (IgG)	90:131	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	1	27	theme	diseases	175:182	arg1	pathogenesis					159:170	pathogenesis	159:170	pathogenesis of diseases	159:182	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	1	27	theme	diseases	175:182	arg1	functions					204:212	the therapeutic functions	188:212	the therapeutic functions of antibody-based drugs	188:236	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	5	28	theme	negative	793:800	arg1	patients					805:812	both rheumatoid factor (RF)-positive and negative RA patients	752:812	both rheumatoid factor (RF)-positive and negative RA patients	752:812	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	4	29	theme	undetected	547:556	arg1	trace					573:577	trace	573:577	trace	573:577	Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans.
28931878	4	29	theme	undetected	547:556	arg1	low-abundance					558:570	these previously undetected low-abundance	530:570	these previously undetected low-abundance	530:570	Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans.
28931878	2	30	theme	microfluidic	386:397	arg1	chip					399:402	a specialized microfluidic chip	372:402	a specialized microfluidic chip	372:402	Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip.
28931878	0	31	theme	sulfated	27:34	arg1	biomarkers					53:62	biomarkers	53:62	biomarkers for rheumatoid arthritis	53:87	A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.
28931878	0	31	theme	sulfated	27:34	arg1	N-glycans					40:48	trace sulfated IgG N-glycans	21:48	trace sulfated IgG N-glycans	21:48	A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.
28931878	2	32	theme	glycomic	310:317	arg1	approach					319:326	a glycomic approach	308:326	a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip	308:402	Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip.
28931878	2	33	theme	specialized	374:384	arg1	chip					399:402	a specialized microfluidic chip	372:402	a specialized microfluidic chip	372:402	Here we show a glycomic approach to detect these species on human IgGs using a specialized microfluidic chip.
28931878	6	34	theme	promising	1047:1055	arg1	glycoforms					1057:1066	promising glycoforms	1047:1066	promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies	1047:1253	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	3	35	theme	sulfated	420:427	arg1	N-glycans					446:454	20 sulfated and 4 acetylated N-glycans	417:454	20 sulfated and 4 acetylated N-glycans on IgGs	417:462	We discover 20 sulfated and 4 acetylated N-glycans on IgGs.
28931878	0	36	theme	trace	21:25	arg1	biomarkers					53:62	biomarkers	53:62	biomarkers for rheumatoid arthritis	53:87	A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.
28931878	0	36	theme	trace	21:25	arg1	N-glycans					40:48	trace sulfated IgG N-glycans	21:48	trace sulfated IgG N-glycans	21:48	A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.
28931878	7	37	theme	rheumatoid	1414:1423	arg1	arthritis					1425:1433	rheumatoid arthritis	1414:1433	rheumatoid arthritis	1414:1433	Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28931878	6	38	theme	infectious	996:1005	arg1	diseases					1007:1014	other autoimmune and infectious diseases	975:1014	other autoimmune and infectious diseases	975:1014	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	6	39	from	function	1147:1154	arg1	disease					1170:1176	disease	1170:1176	disease	1170:1176	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	6	39	from	function	1147:1154	arg1	health					1159:1164	health	1159:1164	health	1159:1164	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	1	40	theme	therapeutic	192:202	arg1	functions					204:212	the therapeutic functions	188:212	the therapeutic functions of antibody-based drugs	188:236	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	6	41	dep	difficult	1217:1225	arg1	using					1227:1231	using	1227:1231	using existing technologies	1227:1253	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	5	42	theme	-positive	870:878	arg1	patients					896:903	the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients	730:903	the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients	730:903	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	0	43	theme	IgG	36:38	arg1	biomarkers					53:62	biomarkers	53:62	biomarkers for rheumatoid arthritis	53:87	A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.
28931878	0	43	theme	IgG	36:38	arg1	N-glycans					40:48	trace sulfated IgG N-glycans	21:48	trace sulfated IgG N-glycans	21:48	A method to identify trace sulfated IgG N-glycans as biomarkers for rheumatoid arthritis.
28931878	7	44	used	used	1391:1394	arg2	biomarkers					1399:1408	biomarkers	1399:1408	biomarkers for rheumatoid arthritis	1399:1433	Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28931878	7	44	used	used	1391:1394	arg2	some					1365:1368	some	1365:1368	some	1365:1368	Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28931878	7	44	used	used	1391:1394	arg2	IgGs					1379:1382	these IgGs	1373:1382	these IgGs	1373:1382	Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28931878	1	45	theme	immunoglobulin	110:123	arg1	G					125:125	immunoglobulin G	110:125	immunoglobulin G (IgG)	110:131	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	1	45	theme	immunoglobulin	110:123	arg1	IgG					128:130	IgG	128:130	IgG	128:130	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	6	46	theme	existing	1233:1240	arg1	technologies					1242:1253	existing technologies	1233:1253	existing technologies	1233:1253	This approach may identify N-glycosylation-associated biomarkers for other autoimmune and infectious diseases and lead to the exploration of promising glycoforms for antibody therapeutics.Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies.
28931878	5	47	theme	negative	884:891	arg1	patients					896:903	the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients	730:903	the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients	730:903	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	1	48	from	glycans	99:105	arg1	G					125:125	immunoglobulin G	110:125	immunoglobulin G (IgG)	110:131	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	1	48	from	glycans	99:105	arg1	IgG					128:130	IgG	128:130	IgG	128:130	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	4	49	theme	ultra-trace	588:598	arg1	N-glycans					600:608	ultra-trace N-glycans	588:608	ultra-trace N-glycans	588:608	Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans.
28931878	5	50	theme	healthy	668:674	arg1	individuals					676:686	141 healthy individuals	664:686	141 healthy individuals	664:686	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	51	theme	RA	893:894	arg1	patients					896:903	the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients	730:903	the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients	730:903	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	1	52	link	N-linked	90:97	arg1	glycans					99:105	N-linked glycans	90:105	N-linked glycans on immunoglobulin G (IgG)	90:131	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	7	53	theme	low-abundance	1328:1340	arg1	N-glycans					1346:1354	low-abundance IgG N-glycans	1328:1354	low-abundance IgG N-glycans	1328:1354	Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28931878	5	54	theme	RA	802:803	arg1	patients					805:812	both rheumatoid factor (RF)-positive and negative RA patients	752:812	both rheumatoid factor (RF)-positive and negative RA patients	752:812	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	7	55	theme	IgG	1342:1344	arg1	N-glycans					1346:1354	low-abundance IgG N-glycans	1328:1354	low-abundance IgG N-glycans	1328:1354	Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28931878	1	56	theme	antibody-based	217:230	arg1	drugs					232:236	antibody-based drugs	217:236	antibody-based drugs	217:236	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	4	57	theme	multiple	471:478	arg1	method					500:505	multiple reaction monitoring method	471:505	multiple reaction monitoring method	471:505	Using multiple reaction monitoring method, we precisely quantify these previously undetected low-abundance, trace and even ultra-trace N-glycans.
28931878	3	58	dep	acetylated	435:444	arg1	4					433:433	4	433:433	4	433:433	We discover 20 sulfated and 4 acetylated N-glycans on IgGs.
28931878	5	59	with	individuals	676:686	arg1	arthritis					645:653	rheumatoid arthritis	634:653	rheumatoid arthritis (RA)	634:658	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	5	59	with	individuals	676:686	arg1	RA					656:657	RA	656:657	RA	656:657	From 277 patients with rheumatoid arthritis (RA) and 141 healthy individuals, we also identify N-glycan biomarkers for the classification of both rheumatoid factor (RF)-positive and negative RA patients, as well as anti-citrullinated protein antibodies (ACPA)-positive and negative RA patients.
28931878	7	60	theme	microfluidic	1283:1294	arg1	method					1296:1301	a microfluidic method	1281:1301	a microfluidic method to identify and quantify low-abundance IgG N-glycans	1281:1354	Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.
28931878	1	61	theme	drugs	232:236	arg1	pathogenesis					159:170	pathogenesis	159:170	pathogenesis of diseases	159:182	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
28931878	1	61	theme	drugs	232:236	arg1	functions					204:212	the therapeutic functions	188:212	the therapeutic functions of antibody-based drugs	188:236	N-linked glycans on immunoglobulin G (IgG) have been associated with pathogenesis of diseases and the therapeutic functions of antibody-based drugs; however, low-abundance species are difficult to detect.
30755292	9	0	theme	Multiple	1628:1635	arg1	clades					1637:1642	CONCLUSION Multiple clades	1617:1642	CONCLUSION Multiple clades	1617:1642	CONCLUSION Multiple clades, some of which differed antigenically from others, co-circulated in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	4	1	from	loss	782:785	arg1	HA					833:834	HA	833:834	HA	833:834	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	2	theme	HA	628:629	arg1	sequences					631:639	the HA sequences	624:639	the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons	624:735	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	6	3	theme	influenza	1161:1169	arg1	season					1171:1176	the 2016/17 influenza season	1149:1176	the 2016/17 influenza season	1149:1176	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	1	4	theme	BACKGROUND	139:148	arg1	virus					168:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	8	5	theme	3C.2A4	1497:1502	arg1	viruses					1504:1510	3C.2A4 viruses	1497:1510	3C.2A4 viruses	1497:1510	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	0	6	theme	viruses	60:66	arg1	characterisation					22:37	Genetic and antigenic characterisation	0:37	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.	0:137	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.
30755292	5	7	theme	ferret	946:951	arg1	antisera					953:960	ferret antisera	946:960	ferret antisera obtained from experimentally infected ferrets	946:1006	We also examined the antigenicity of isolates using ferret antisera obtained from experimentally infected ferrets.
30755292	6	8	theme	RESULTS	1009:1015	arg1	H3N2					1029:1032	H3N2	1029:1032	H3N2	1029:1032	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	8	theme	RESULTS	1009:1015	arg1	A					1027:1027	RESULTS Influenza A	1009:1027	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4)	1009:1126	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	2	9	theme	genetic	310:316	arg1	analyses					332:339	continuous genetic and antigenic analyses	299:339	continuous genetic and antigenic analyses of A(H3N2) virus	299:356	Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.
30755292	6	10	theme	2016/17	1153:1159	arg1	season					1171:1176	the 2016/17 influenza season	1149:1176	the 2016/17 influenza season	1149:1176	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	4	11	theme	sites	824:828	arg1	gain					790:793	gain	790:793	gain	790:793	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	11	theme	sites	824:828	arg1	substitutions					760:772	amino acid substitutions	749:772	amino acid substitutions	749:772	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	11	theme	sites	824:828	arg1	loss					782:785	loss	782:785	loss	782:785	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	8	12	theme	distinct	1526:1533	arg1	differences					1545:1555	distinct antigenic differences	1526:1555	distinct antigenic differences from each other and from other clades in the antigenic map	1526:1614	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	9	13	theme	influenza	1759:1767	arg1	seasons					1769:1775	the 2016/17 and 2017/18 influenza seasons	1735:1775	the 2016/17 and 2017/18 influenza seasons	1735:1775	CONCLUSION Multiple clades, some of which differed antigenically from others, co-circulated in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	3	14	theme	epidemic	491:498	arg1	trend					500:504	the epidemic trend	487:504	the epidemic trend of A(H3N2) virus infection in Yokohama, Japan	487:550	AIM We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	3	15	from	trend	500:504	arg1	Japan					546:550	Japan	546:550	Japan	546:550	AIM We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	4	16	gly	N-glycosylation	808:822	arg2	sites					824:828	potential N-glycosylation sites	798:828	potential N-glycosylation sites	798:828	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	17	from	substitutions	760:772	arg1	HA					833:834	HA	833:834	HA	833:834	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	6	18	dep	clades	1220:1225	arg1	clades					1220:1225	clades 3C.2A1b and 3C.2A2	1220:1244	clades 3C.2A1b and 3C.2A2	1220:1244	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	18	dep	clades	1220:1225	arg1	3C.2A2					1239:1244	3C.2A2	1239:1244	3C.2A2	1239:1244	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	18	dep	clades	1220:1225	arg1	3C.2A1b					1227:1233	3C.2A1b	1227:1233	3C.2A1b	1227:1233	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	8	19	from	differences	1545:1555	arg1	map					1612:1614	the antigenic map	1598:1614	the antigenic map	1598:1614	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	3	20	dep	AIM	424:426	arg1	We					428:429	We	428:429	We	428:429	AIM We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	6	21	theme	A	1027:1027	arg1	viruses					1035:1041	RESULTS Influenza A(H3N2) viruses	1009:1041	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4)	1009:1126	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	8	22	dep	clade	1480:1484	arg1	3C.2A2					1486:1491	3C.2A2	1486:1491	clade 3C.2A2	1480:1491	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	4	23	theme	amino	749:753	arg1	substitutions					760:772	amino acid substitutions	749:772	amino acid substitutions	749:772	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	2	24	theme	A	344:344	arg1	virus					352:356	A(H3N2) virus	344:356	A(H3N2) virus	344:356	Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.
30755292	1	25	theme	A	160:160	arg1	virus					168:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	8	26	from	clades	1588:1593	arg1	differences					1545:1555	distinct antigenic differences	1526:1555	distinct antigenic differences from each other and from other clades in the antigenic map	1526:1614	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	6	27	theme	influenza	1276:1284	arg1	season					1286:1291	the 2017/18 influenza season	1264:1291	the 2017/18 influenza season	1264:1291	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	0	28	theme	Genetic	0:6	arg1	characterisation					22:37	Genetic and antigenic characterisation	0:37	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.	0:137	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.
30755292	8	29	from	other	1567:1571	arg1	differences					1545:1555	distinct antigenic differences	1526:1555	distinct antigenic differences from each other and from other clades in the antigenic map	1526:1614	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	8	30	theme	other	1582:1586	arg1	clades					1588:1593	other clades	1582:1593	other clades	1582:1593	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	1	31	theme	H3N2	162:165	arg1	virus					168:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	2	32	theme	antigenic	382:390	arg1	mutants					392:398	antigenic mutants	382:398	antigenic mutants	382:398	Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.
30755292	8	33	theme	Antigenic	1405:1413	arg1	analysis					1415:1422	Antigenic analysis	1405:1422	Antigenic analysis	1405:1422	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	4	34	theme	acid	755:758	arg1	substitutions					760:772	amino acid substitutions	749:772	amino acid substitutions	749:772	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	7	35	theme	N-linked	1345:1352	arg1	site					1368:1371	one N-linked glycosylation site	1341:1371	one N-linked glycosylation site in HA relative to other clades	1341:1402	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	3	36	theme	H3N2	511:514	arg1	virus					517:521	A(H3N2) virus	509:521	A(H3N2) virus infection	509:531	AIM We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	5	37	theme	infected	991:998	arg1	ferrets					1000:1006	experimentally infected ferrets	976:1006	experimentally infected ferrets	976:1006	We also examined the antigenicity of isolates using ferret antisera obtained from experimentally infected ferrets.
30755292	8	38	theme	antigenic	1433:1441	arg1	differences					1443:1453	antigenic differences	1433:1453	antigenic differences	1433:1453	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	4	39	theme	influenza	719:727	arg1	seasons					729:735	the 2016/17 and 2017/18 influenza seasons	695:735	the 2016/17 and 2017/18 influenza seasons	695:735	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	0	40	theme	antigenic	12:20	arg1	characterisation					22:37	Genetic and antigenic characterisation	0:37	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.	0:137	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.
30755292	8	41	theme	antigenic	1602:1610	arg1	map					1612:1614	the antigenic map	1598:1614	the antigenic map	1598:1614	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	1	42	from	changes	236:242	arg1	antigenicity					251:262	the antigenicity	247:262	the antigenicity of haemagglutinin (HA)	247:285	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	6	43	theme	2017/18	1268:1274	arg1	season					1286:1291	the 2017/18 influenza season	1264:1291	the 2017/18 influenza season	1264:1291	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	1	44	theme	Influenza	150:158	arg1	virus					168:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus	139:172	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	0	45	theme	influenza	42:50	arg1	H3N2					54:57	H3N2	54:57	H3N2	54:57	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.
30755292	0	45	theme	influenza	42:50	arg1	A					52:52	influenza A	42:52	influenza A(H3N2) viruses	42:66	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.
30755292	0	46	theme	influenza	120:128	arg1	seasons					130:136	the 2016/17 and 2017/18 influenza seasons	96:136	the 2016/17 and 2017/18 influenza seasons	96:136	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.
30755292	4	47	from	HA	833:834	arg1	gain					790:793	gain	790:793	gain	790:793	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	47	from	HA	833:834	arg1	substitutions					760:772	amino acid substitutions	749:772	amino acid substitutions	749:772	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	47	from	HA	833:834	arg1	loss					782:785	loss	782:785	loss	782:785	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	3	48	theme	infection	523:531	arg1	trend					500:504	the epidemic trend	487:504	the epidemic trend of A(H3N2) virus infection in Yokohama, Japan	487:550	AIM We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	7	49	link	N-linked	1345:1352	arg1	site					1368:1371	one N-linked glycosylation site	1341:1371	one N-linked glycosylation site in HA relative to other clades	1341:1402	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	2	50	theme	virus	352:356	arg1	analyses					332:339	continuous genetic and antigenic analyses	299:339	continuous genetic and antigenic analyses of A(H3N2) virus	299:356	Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.
30755292	2	51	theme	H3N2	346:349	arg1	virus					352:356	A(H3N2) virus	344:356	A(H3N2) virus	344:356	Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.
30755292	1	52	theme	haemagglutinin	267:280	arg1	antigenicity					251:262	the antigenicity	247:262	the antigenicity of haemagglutinin (HA)	247:285	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	4	53	theme	HA	890:891	arg1	antigenicity					874:885	the antigenicity	870:885	the antigenicity of HA	870:891	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	7	54	theme	relative	1379:1386	arg1	HA					1376:1377	HA	1376:1377	HA relative to other clades	1376:1402	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	6	55	dep	clades	1068:1073	arg1	3C.2A1b					1092:1098	3C.2A1b	1092:1098	3C.2A1b	1092:1098	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	55	dep	clades	1068:1073	arg1	3C.2A4					1120:1125	3C.2A4	1120:1125	3C.2A4	1120:1125	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	55	dep	clades	1068:1073	arg1	clades					1068:1073	clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4	1068:1125	clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4	1068:1125	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	55	dep	clades	1068:1073	arg1	3C.2A1					1075:1080	3C.2A1	1075:1080	3C.2A1	1075:1080	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	55	dep	clades	1068:1073	arg1	3C.2A2					1101:1106	3C.2A2	1101:1106	3C.2A2	1101:1106	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	55	dep	clades	1068:1073	arg1	3C.2A3					1109:1114	3C.2A3	1109:1114	3C.2A3	1109:1114	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	55	dep	clades	1068:1073	arg1	3C.2A1a					1083:1089	3C.2A1a	1083:1089	3C.2A1a	1083:1089	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	7	56	dep	clades	1310:1315	arg1	3C.2A1a					1317:1323	3C.2A1a	1317:1323	3C.2A1a	1317:1323	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	7	56	dep	clades	1310:1315	arg1	clades					1310:1315	clades 3C.2A1a and 3C.2A3	1310:1334	clades 3C.2A1a and 3C.2A3	1310:1334	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	7	56	dep	clades	1310:1315	arg1	3C.2A3					1329:1334	3C.2A3	1329:1334	3C.2A3	1329:1334	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	7	57	from	isolates	1298:1305	arg1	3C.2A1a					1317:1323	3C.2A1a	1317:1323	3C.2A1a	1317:1323	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	7	57	from	isolates	1298:1305	arg1	clades					1310:1315	clades 3C.2A1a and 3C.2A3	1310:1334	clades 3C.2A1a and 3C.2A3	1310:1334	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	7	57	from	isolates	1298:1305	arg1	3C.2A3					1329:1334	3C.2A3	1329:1334	3C.2A3	1329:1334	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	4	58	from	sites	824:828	arg1	HA					833:834	HA	833:834	HA	833:834	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	2	59	theme	continuous	299:308	arg1	analyses					332:339	continuous genetic and antigenic analyses	299:339	continuous genetic and antigenic analyses of A(H3N2) virus	299:356	Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.
30755292	0	60	theme	A	52:52	arg1	viruses					60:66	influenza A(H3N2) viruses	42:66	influenza A(H3N2) viruses	42:66	Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.
30755292	5	61	theme	isolates	931:938	arg1	antigenicity					915:926	the antigenicity	911:926	the antigenicity of isolates	911:938	We also examined the antigenicity of isolates using ferret antisera obtained from experimentally infected ferrets.
30755292	3	62	theme	virus	517:521	arg1	infection					523:531	A(H3N2) virus infection	509:531	A(H3N2) virus infection	509:531	AIM We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	4	63	dep	loss	782:785	arg1	the					778:780	the	778:780	the	778:780	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	64	located	detected	660:667	arg2	viruses					652:658	A(H3N2) viruses	644:658	A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons	644:735	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	64	located	detected	660:667	arg1	Japan					682:686	Japan	682:686	Japan	682:686	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	65	theme	N-glycosylation	808:822	arg1	sites					824:828	potential N-glycosylation sites	798:828	potential N-glycosylation sites	798:828	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	7	66	theme	glycosylation	1354:1366	arg1	site					1368:1371	one N-linked glycosylation site	1341:1371	one N-linked glycosylation site in HA relative to other clades	1341:1402	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	4	67	dep	METHODS	602:608	arg1	determined					613:622	determined	613:622	determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA	613:891	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	68	theme	potential	798:806	arg1	sites					824:828	potential N-glycosylation sites	798:828	potential N-glycosylation sites	798:828	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	3	69	theme	influenza	583:591	arg1	seasons					593:599	the 2016/17 and 2017/18 influenza seasons	559:599	the 2016/17 and 2017/18 influenza seasons	559:599	AIM We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	4	70	theme	viruses	652:658	arg1	sequences					631:639	the HA sequences	624:639	the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons	624:735	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	4	71	theme	A	644:644	arg1	viruses					652:658	A(H3N2) viruses	644:658	A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons	644:735	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	8	72	theme	antigenic	1535:1543	arg1	differences					1545:1555	distinct antigenic differences	1526:1555	distinct antigenic differences from each other and from other clades in the antigenic map	1526:1614	Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.
30755292	1	73	theme	human	199:203	arg1	responses					212:220	human immune responses	199:220	human immune responses	199:220	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	4	74	from	gain	790:793	arg1	HA					833:834	HA	833:834	HA	833:834	METHODS We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA.
30755292	9	75	theme	CONCLUSION	1617:1626	arg1	clades					1637:1642	CONCLUSION Multiple clades	1617:1642	CONCLUSION Multiple clades	1617:1642	CONCLUSION Multiple clades, some of which differed antigenically from others, co-circulated in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.
30755292	6	76	theme	Influenza	1017:1025	arg1	H3N2					1029:1032	H3N2	1029:1032	H3N2	1029:1032	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	6	76	theme	Influenza	1017:1025	arg1	A					1027:1027	RESULTS Influenza A	1009:1027	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4)	1009:1126	RESULTS Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season.
30755292	7	77	gly	glycosylation	1354:1366	arg2	one					1341:1343	one	1341:1343	one	1341:1343	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	7	77	gly	glycosylation	1354:1366	arg2	site					1368:1371	one N-linked glycosylation site	1341:1371	one N-linked glycosylation site in HA relative to other clades	1341:1402	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	1	78	theme	immune	205:210	arg1	responses					212:220	human immune responses	199:220	human immune responses	199:220	BACKGROUND Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA).
30755292	7	79	from	site	1368:1371	arg1	HA					1376:1377	HA	1376:1377	HA relative to other clades	1376:1402	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30755292	2	80	theme	antigenic	322:330	arg1	analyses					332:339	continuous genetic and antigenic analyses	299:339	continuous genetic and antigenic analyses of A(H3N2) virus	299:356	Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.
30755292	7	81	theme	other	1391:1395	arg1	clades					1397:1402	other clades	1391:1402	other clades	1391:1402	The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades.
30535277	3	0	theme	healthy	503:509	arg1	HV					523:524	HV	523:524	HV	523:524	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	0	theme	healthy	503:509	arg1	volunteers					511:520	30 healthy volunteers	500:520	30 healthy volunteers (HV)	500:525	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	7	1	theme	HC	1291:1292	arg1	saliva					1273:1278	saliva	1273:1278	saliva of HV, HB, HC, and HCC	1273:1301	Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC.
30535277	8	2	theme	HBV-induced	1492:1502	arg1	diseases					1510:1517	HBV-induced liver diseases	1492:1517	HBV-induced liver diseases	1492:1517	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	7	3	theme	HB	1287:1288	arg1	saliva					1273:1278	saliva	1273:1278	saliva of HV, HB, HC, and HCC	1273:1301	Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC.
30535277	7	4	theme	HCC	1299:1301	arg1	saliva					1273:1278	saliva	1273:1278	saliva of HV, HB, HC, and HCC	1273:1301	Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC.
30535277	7	5	theme	HV	1283:1284	arg1	saliva					1273:1278	saliva	1273:1278	saliva of HV, HB, HC, and HCC	1273:1301	Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC.
30535277	10	6	theme	biomarkers	1701:1710	arg1	discovery					1688:1696	the discovery	1684:1696	the discovery of biomarkers for HC and HCC	1684:1725	This study could facilitate the discovery of biomarkers for HC and HCC based on precise alterations of fucosylated N/O-glycans in saliva.
30535277	3	7	from	subjects	490:497	arg1	saliva					474:479	saliva	474:479	saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC))	474:655	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	2	8	theme	N-linked	304:311	arg1	glycans					313:319	salivary N-linked glycans	295:319	salivary N-linked glycans related to the development of HBV-infected liver diseases	295:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
30535277	1	9	theme	-induced	177:184	arg1	threats					228:234	serious health threats worldwide	213:244	serious health threats worldwide	213:244	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	1	9	theme	-induced	177:184	arg1	diseases					200:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	4	10	theme	<	858:858	arg1	subjects					846:853	other subjects	840:853	other subjects (P < 0.0001)	840:866	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	4	10	theme	<	858:858	arg1	P					856:856	P < 0.0001	856:865	P < 0.0001	856:865	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	6	11	theme	isolated	1043:1050	arg1	glycoproteins					1052:1064	the isolated glycoproteins	1039:1064	the isolated glycoproteins with PNGase F and NaClO	1039:1088	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	3	12	theme	salivary	663:670	arg1	microarrys					672:681	salivary microarrys	663:681	salivary microarrys	663:681	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	1	13	theme	liver	194:198	arg1	threats					228:234	serious health threats worldwide	213:244	serious health threats worldwide	213:244	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	1	13	theme	liver	194:198	arg1	diseases					200:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	0	14	theme	carcinoma	139:147	arg1	saliva					68:73	saliva	68:73	saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma	68:147	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	5	15	theme	particle	980:987	arg1	conjugates					989:998	LTL-magnetic particle conjugates	967:998	LTL-magnetic particle conjugates	967:998	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	4	16	theme	other	840:844	arg1	subjects					846:853	other subjects	840:853	other subjects (P < 0.0001)	840:866	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	4	16	theme	other	840:844	arg1	P					856:856	P < 0.0001	856:865	P < 0.0001	856:865	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	5	17	theme	HC	952:953	arg1	saliva					934:939	pooled saliva	927:939	pooled saliva of HV, HB, HC, and HCC	927:962	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	6	18	with	glycoproteins	1052:1064	arg1	F					1078:1078	PNGase F	1071:1078	PNGase F	1071:1078	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	6	18	with	glycoproteins	1052:1064	arg1	NaClO					1084:1088	NaClO	1084:1088	NaClO	1084:1088	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	9	19	theme	N-glycan	1524:1531	arg1	m/z					1539:1541	m/z 2205.766	1539:1550	m/z 2205.766	1539:1550	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	9	19	theme	N-glycan	1524:1531	arg1	peak					1533:1536	One N-glycan peak	1520:1536	One N-glycan peak (m/z 2205.766)	1520:1551	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	8	20	attach	presented	1465:1473	arg2	peaks					1343:1347	8 N-glycan peaks	1332:1347	8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036)	1332:1391	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	8	20	attach	presented	1465:1473	arg2	peaks					1409:1413	15 O-glycan peaks	1397:1413	15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444)	1397:1453	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	8	20	attach	presented	1465:1473	arg1	patients					1478:1485	patients	1478:1485	patients with HBV-induced liver diseases	1478:1517	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	9	21	from	HCC	1651:1653	arg1	unique					1641:1646	unique	1641:1646	unique	1641:1646	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	3	22	theme	hepatic	580:586	arg1	HC					599:600	HC	599:600	HC	599:600	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	22	theme	hepatic	580:586	arg1	cirrhosis					588:596	hepatic cirrhosis	580:596	hepatic cirrhosis (HC)	580:601	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	5	23	gly	glycoproteins	894:906	arg1	glycoproteins					894:906	the fucosylated glycoproteins	878:906	the fucosylated glycoproteins	878:906	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	9	24	from	unique	1641:1646	arg1	HCC					1651:1653	HCC	1651:1653	HCC	1651:1653	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	3	25	with	patients	566:573	arg1	cirrhosis					588:596	hepatic cirrhosis	580:596	hepatic cirrhosis (HC)	580:601	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	25	with	patients	566:573	arg1	HC					599:600	HC	599:600	HC	599:600	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	25	with	patients	566:573	arg1	B					555:555	hepatitis B	545:555	hepatitis B (HB)	545:560	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	25	with	patients	566:573	arg1	carcinoma					640:648	hepatocellular carcinoma	625:648	hepatocellular carcinoma (HCC)	625:654	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	25	with	patients	566:573	arg1	HB					558:559	HB	558:559	HB	558:559	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	25	with	patients	566:573	arg1	HCC					651:653	HCC	651:653	HCC	651:653	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	1	26	theme	hepatitis	154:162	arg1	HBV					173:175	HBV	173:175	HBV	173:175	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	1	26	theme	hepatitis	154:162	arg1	virus					166:170	The hepatitis B virus	150:170	The hepatitis B virus (HBV)	150:176	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	0	27	theme	HBV-induced	78:88	arg1	hepatitis					98:106	HBV-induced chronic hepatitis	78:106	HBV-induced chronic hepatitis	78:106	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	8	28	dep	1177.407	1422:1429	arg1	e.g.					1416:1419	e.g.	1416:1419	e.g.	1416:1419	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	8	29	theme	N-glycan	1334:1341	arg1	peaks					1343:1347	8 N-glycan peaks	1332:1347	8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036)	1332:1391	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	10	30	theme	fucosylated	1759:1769	arg1	N/O-glycans					1771:1781	fucosylated N/O-glycans	1759:1781	fucosylated N/O-glycans	1759:1781	This study could facilitate the discovery of biomarkers for HC and HCC based on precise alterations of fucosylated N/O-glycans in saliva.
30535277	0	31	theme	hepatitis	98:106	arg1	saliva					68:73	saliva	68:73	saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma	68:147	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	3	32	theme	N/O-glycans	441:451	arg1	alterations					414:424	the alterations	410:424	the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC))	410:655	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	0	33	theme	cirrhosis	109:117	arg1	saliva					68:73	saliva	68:73	saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma	68:147	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	4	34	gly	fucosylated	753:763	arg1	glycans					765:771	fucosylated glycans	753:771	fucosylated glycans recognized by LTL	753:789	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	7	35	theme	N/O-glycan	1193:1202	arg1	peaks					1204:1208	21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks	1162:1208	21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC	1162:1301	Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC.
30535277	0	36	theme	abnormal	18:25	arg1	fucosylated-glycans					27:45	abnormal fucosylated-glycans	18:45	abnormal fucosylated-glycans	18:45	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	4	37	theme	fucosylated	753:763	arg1	glycans					765:771	fucosylated glycans	753:771	fucosylated glycans recognized by LTL	753:789	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	8	38	with	patients	1478:1485	arg1	diseases					1510:1517	HBV-induced liver diseases	1492:1517	HBV-induced liver diseases	1492:1517	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	10	39	gly	fucosylated	1759:1769	arg1	N/O-glycans					1771:1781	fucosylated N/O-glycans	1759:1781	fucosylated N/O-glycans	1759:1781	This study could facilitate the discovery of biomarkers for HC and HCC based on precise alterations of fucosylated N/O-glycans in saliva.
30535277	9	40	theme	m/z	1599:1601	arg1	1157.420					1603:1610	m/z 1157.420	1599:1610	m/z 1157.420	1599:1610	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	1	41	theme	serious	213:219	arg1	threats					228:234	serious health threats worldwide	213:244	serious health threats worldwide	213:244	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	1	41	theme	serious	213:219	arg1	diseases					200:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	5	42	theme	pooled	927:932	arg1	saliva					934:939	pooled saliva	927:939	pooled saliva of HV, HB, HC, and HCC	927:962	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	8	43	theme	O-glycan	1400:1407	arg1	peaks					1409:1413	15 O-glycan peaks	1397:1413	15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444)	1397:1453	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	3	44	gly	fucosylated	429:439	arg1	N/O-glycans					441:451	fucosylated N/O-glycans	429:451	fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC))	429:655	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	2	45	theme	diseases	370:377	arg1	development					336:346	the development	332:346	the development of HBV-infected liver diseases	332:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
30535277	2	46	theme	HBV-infected	351:362	arg1	diseases					370:377	HBV-infected liver diseases	351:377	HBV-infected liver diseases	351:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
30535277	8	47	dep	peaks	1343:1347	arg1	2158.777					1370:1377	2158.777	1370:1377	2158.777	1370:1377	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	8	47	dep	peaks	1343:1347	arg1	2905.036					1383:1390	2905.036	1383:1390	2905.036	1383:1390	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	3	48	theme	hepatocellular	625:638	arg1	carcinoma					640:648	hepatocellular carcinoma	625:648	hepatocellular carcinoma (HCC)	625:654	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	48	theme	hepatocellular	625:638	arg1	HCC					651:653	HCC	651:653	HCC	651:653	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	49	with	volunteers	511:520	arg1	cirrhosis					588:596	hepatic cirrhosis	580:596	hepatic cirrhosis (HC)	580:601	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	49	with	volunteers	511:520	arg1	HC					599:600	HC	599:600	HC	599:600	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	49	with	volunteers	511:520	arg1	B					555:555	hepatitis B	545:555	hepatitis B (HB)	545:560	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	49	with	volunteers	511:520	arg1	carcinoma					640:648	hepatocellular carcinoma	625:648	hepatocellular carcinoma (HCC)	625:654	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	49	with	volunteers	511:520	arg1	HB					558:559	HB	558:559	HB	558:559	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	49	with	volunteers	511:520	arg1	HCC					651:653	HCC	651:653	HCC	651:653	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	50	theme	hepatitis	545:553	arg1	HB					558:559	HB	558:559	HB	558:559	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	50	theme	hepatitis	545:553	arg1	B					555:555	hepatitis B	545:555	hepatitis B (HB)	545:560	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	8	51	theme	liver	1504:1508	arg1	diseases					1510:1517	HBV-induced liver diseases	1492:1517	HBV-induced liver diseases	1492:1517	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	6	52	theme	PNGase	1071:1076	arg1	F					1078:1078	PNGase F	1071:1078	PNGase F	1071:1078	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	6	53	gly	glycoproteins	1052:1064	arg1	glycoproteins					1052:1064	the isolated glycoproteins	1039:1064	the isolated glycoproteins with PNGase F and NaClO	1039:1088	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	2	54	theme	glycans	313:319	arg1	alterations					280:290	the alterations	276:290	the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases	276:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
30535277	3	55	with	patients	611:618	arg1	cirrhosis					588:596	hepatic cirrhosis	580:596	hepatic cirrhosis (HC)	580:601	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	55	with	patients	611:618	arg1	HC					599:600	HC	599:600	HC	599:600	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	55	with	patients	611:618	arg1	B					555:555	hepatitis B	545:555	hepatitis B (HB)	545:560	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	55	with	patients	611:618	arg1	carcinoma					640:648	hepatocellular carcinoma	625:648	hepatocellular carcinoma (HCC)	625:654	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	55	with	patients	611:618	arg1	HB					558:559	HB	558:559	HB	558:559	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	55	with	patients	611:618	arg1	HCC					651:653	HCC	651:653	HCC	651:653	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	0	56	theme	hepatocellular	124:137	arg1	carcinoma					139:147	hepatocellular carcinoma	124:147	hepatocellular carcinoma	124:147	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	2	57	theme	salivary	295:302	arg1	glycans					313:319	salivary N-linked glycans	295:319	salivary N-linked glycans related to the development of HBV-infected liver diseases	295:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
30535277	1	58	theme	chronic	186:192	arg1	threats					228:234	serious health threats worldwide	213:244	serious health threats worldwide	213:244	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	1	58	theme	chronic	186:192	arg1	diseases					200:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	5	59	attach	isolated	913:920	arg1	saliva					934:939	pooled saliva	927:939	pooled saliva of HV, HB, HC, and HCC	927:962	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	5	59	attach	isolated	913:920	arg2	glycoproteins					894:906	the fucosylated glycoproteins	878:906	the fucosylated glycoproteins	878:906	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	1	60	dep	threats	228:234	arg1	worldwide					236:244	worldwide	236:244	serious health threats worldwide	213:244	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	5	61	theme	LTL-magnetic	967:978	arg1	conjugates					989:998	LTL-magnetic particle conjugates	967:998	LTL-magnetic particle conjugates	967:998	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	7	62	theme	proposed	1250:1257	arg1	structures					1259:1268	proposed structures	1250:1268	proposed structures	1250:1268	Totally, there were 21/20, 25/18, 29/19, and 28/24 N/O-glycan peaks that were identified and annotated with proposed structures in saliva of HV, HB, HC, and HCC.
30535277	2	63	link	N-linked	304:311	arg1	glycans					313:319	salivary N-linked glycans	295:319	salivary N-linked glycans related to the development of HBV-infected liver diseases	295:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
30535277	10	64	theme	precise	1736:1742	arg1	alterations					1744:1754	precise alterations	1736:1754	precise alterations of fucosylated N/O-glycans	1736:1781	This study could facilitate the discovery of biomarkers for HC and HCC based on precise alterations of fucosylated N/O-glycans in saliva.
30535277	5	65	theme	HCC	960:962	arg1	saliva					934:939	pooled saliva	927:939	pooled saliva of HV, HB, HC, and HCC	927:962	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	5	66	gly	fucosylated	882:892	arg1	glycoproteins					894:906	the fucosylated glycoproteins	878:906	the fucosylated glycoproteins	878:906	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	8	67	dep	m/z	1356:1358	arg1	e.g.					1350:1353	e.g.	1350:1353	e.g.	1350:1353	Among the total, there were 8 N-glycan peaks (e.g., m/z 1905.634, 2158.777 and 2905.036) and 15 O-glycan peaks (e.g., 1177.407, 1308.444 and 1322.444) that only presented in patients with HBV-induced liver diseases.
30535277	0	68	theme	chronic	90:96	arg1	hepatitis					98:106	HBV-induced chronic hepatitis	78:106	HBV-induced chronic hepatitis	78:106	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	1	69	theme	B	164:164	arg1	HBV					173:175	HBV	173:175	HBV	173:175	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	1	69	theme	B	164:164	arg1	virus					166:170	The hepatitis B virus	150:170	The hepatitis B virus (HBV)	150:176	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	10	70	theme	N/O-glycans	1771:1781	arg1	alterations					1744:1754	precise alterations	1736:1754	precise alterations of fucosylated N/O-glycans	1736:1781	This study could facilitate the discovery of biomarkers for HC and HCC based on precise alterations of fucosylated N/O-glycans in saliva.
30535277	5	71	theme	fucosylated	882:892	arg1	glycoproteins					894:906	the fucosylated glycoproteins	878:906	the fucosylated glycoproteins	878:906	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	9	72	dep	1157.420	1603:1610	arg1	e.g.					1593:1596	e.g.	1593:1596	e.g.	1593:1596	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	3	73	dep	subjects	490:497	arg1	patients					566:573	30 patients	563:573	30 patients with hepatic cirrhosis (HC)	563:601	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	73	dep	subjects	490:497	arg1	HV					523:524	HV	523:524	HV	523:524	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	73	dep	subjects	490:497	arg1	volunteers					511:520	30 healthy volunteers	500:520	30 healthy volunteers (HV)	500:525	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	73	dep	subjects	490:497	arg1	patients					531:538	30 patients	528:538	30 patients with hepatitis B (HB)	528:560	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	73	dep	subjects	490:497	arg1	patients					611:618	30 patients	608:618	30 patients with hepatocellular carcinoma (HCC)	608:654	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	74	with	patients	531:538	arg1	cirrhosis					588:596	hepatic cirrhosis	580:596	hepatic cirrhosis (HC)	580:601	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	74	with	patients	531:538	arg1	HC					599:600	HC	599:600	HC	599:600	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	74	with	patients	531:538	arg1	B					555:555	hepatitis B	545:555	hepatitis B (HB)	545:560	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	74	with	patients	531:538	arg1	carcinoma					640:648	hepatocellular carcinoma	625:648	hepatocellular carcinoma (HCC)	625:654	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	74	with	patients	531:538	arg1	HB					558:559	HB	558:559	HB	558:559	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	74	with	patients	531:538	arg1	HCC					651:653	HCC	651:653	HCC	651:653	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	3	75	theme	fucosylated	429:439	arg1	N/O-glycans					441:451	fucosylated N/O-glycans	429:451	fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC))	429:655	Here, we further investigated the alterations of fucosylated N/O-glycans recognized by LTL in saliva from 120 subjects (30 healthy volunteers (HV), 30 patients with hepatitis B (HB), 30 patients with hepatic cirrhosis (HC), and 30 patients with hepatocellular carcinoma (HCC)) using salivary microarrys and MALDI-TOF/TOF-MS.
30535277	0	76	theme	fucosylated-glycans	27:45	arg1	Identification					0:13	Identification	0:13	Identification of abnormal fucosylated-glycans	0:45	Identification of abnormal fucosylated-glycans recognized by LTL in saliva of HBV-induced chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
30535277	9	77	theme	O-glycan	1577:1584	arg1	peaks					1586:1590	9 O-glycan peaks	1575:1590	9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402)	1575:1634	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	9	78	from	HC	1567:1568	arg1	unique					1557:1562	unique	1557:1562	unique	1557:1562	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	5	79	theme	HV	944:945	arg1	saliva					934:939	pooled saliva	927:939	pooled saliva of HV, HB, HC, and HCC	927:962	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	9	80	from	unique	1557:1562	arg1	HC					1567:1568	HC	1567:1568	HC	1567:1568	One N-glycan peak (m/z 2205.766) was unique in HC, and 9 O-glycan peaks (e.g., m/z 1157.420, 1163.417 and 1193.402) were unique in HCC.
30535277	5	81	theme	HB	948:949	arg1	saliva					934:939	pooled saliva	927:939	pooled saliva of HV, HB, HC, and HCC	927:962	Besides, the fucosylated glycoproteins were isolated from pooled saliva of HV, HB, HC, and HCC by LTL-magnetic particle conjugates.
30535277	6	82	attach	released	1025:1032	arg1	glycoproteins					1052:1064	the isolated glycoproteins	1039:1064	the isolated glycoproteins with PNGase F and NaClO	1039:1088	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	6	82	attach	released	1025:1032	arg2	glycans					1012:1018	N/O- glycans	1007:1018	N/O- glycans	1007:1018	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	4	83	theme	glycans	765:771	arg1	level					744:748	the expression level	729:748	the expression level of fucosylated glycans recognized by LTL	729:789	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	2	84	theme	related	321:327	arg1	glycans					313:319	salivary N-linked glycans	295:319	salivary N-linked glycans related to the development of HBV-infected liver diseases	295:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
30535277	1	85	theme	health	221:226	arg1	threats					228:234	serious health threats worldwide	213:244	serious health threats worldwide	213:244	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	1	85	theme	health	221:226	arg1	diseases					200:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases	150:207	The hepatitis B virus (HBV)-induced chronic liver diseases are serious health threats worldwide.
30535277	6	86	theme	N/O-	1007:1010	arg1	glycans					1012:1018	N/O- glycans	1007:1018	N/O- glycans	1007:1018	Then, N/O- glycans were released from the isolated glycoproteins with PNGase F and NaClO, and were identified by MALDI-TOF-MS, respectively.
30535277	4	87	theme	expression	733:742	arg1	level					744:748	the expression level	729:748	the expression level of fucosylated glycans recognized by LTL	729:789	The results showed that the expression level of fucosylated glycans recognized by LTL was significantly increased in HCC compared with other subjects (P < 0.0001).
30535277	2	88	theme	liver	364:368	arg1	diseases					370:377	HBV-infected liver diseases	351:377	HBV-infected liver diseases	351:377	There is evidence to display the alterations of salivary N-linked glycans related to the development of HBV-infected liver diseases.
29967251	4	0	theme	nanoparticle	928:939	arg1	formulation					941:951	a nanoparticle formulation	926:951	a nanoparticle formulation validated by in vivo molecular imaging	926:990	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	10	1	theme	CD8-EGFR	1651:1658	arg1	Expression					1633:1642	Expression	1633:1642	Expression of the CD8-EGFR	1633:1658	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	3	2	theme	DNA	749:751	arg1	damage					753:758	DNA damage	749:758	DNA damage	749:758	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	11	3	dep	CONCLUSIONS	1825:1835	arg1	suggests					1848:1855	suggests	1848:1855	suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455	1848:2044	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	9	4	theme	xenografts	1522:1531	arg1	treatment					1502:1510	Combined treatment	1493:1510	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1	1493:1572	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls.
29967251	3	5	theme	cell-cycle	765:774	arg1	arrest					776:781	cell-cycle arrest	765:781	cell-cycle arrest	765:781	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	2	6	theme	endoplasmic	300:310	arg1	reticulum					312:320	an endoplasmic reticulum	297:320	an endoplasmic reticulum co-	297:324	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	1	7	theme	-targeted	199:207	arg1	therapies					209:217	receptor tyrosine kinase (RTK)-targeted therapies	169:217	receptor tyrosine kinase (RTK)-targeted therapies	169:217	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	10	8	theme	DNA	1706:1708	arg1	damage					1710:1715	DNA damage	1706:1715	DNA damage	1706:1715	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	2	9	theme	crucial	361:367	arg1	co-					322:324	an endoplasmic reticulum co-	297:324	an endoplasmic reticulum co-	297:324	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	9	theme	crucial	361:367	arg1	glycosylation					282:294	protein N-linked glycosylation	265:294	protein N-linked glycosylation	265:294	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	11	10	theme	novel	1915:1919	arg1	inhibition					1888:1897	oligosaccharyltransferase inhibition	1862:1897	oligosaccharyltransferase inhibition with NGI-1	1862:1908	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	11	10	theme	novel	1915:1919	arg1	approach					1921:1928	a novel approach	1913:1928	a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455	1913:2044	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	2	11	theme	posttranslational	330:346	arg1	modification					348:359	posttranslational modification	330:359	posttranslational modification	330:359	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	11	theme	posttranslational	330:346	arg1	glycosylation					282:294	protein N-linked glycosylation	265:294	protein N-linked glycosylation	265:294	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	10	12	theme	cellular	1722:1729	arg1	radiosensitivity					1731:1746	cellular radiosensitivity	1722:1746	cellular radiosensitivity	1722:1746	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	3	13	theme	expression	840:849	arg1	profiles					851:858	glioma cell receptor expression profiles	819:858	glioma cell receptor expression profiles	819:858	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	9	14	theme	tumor	1596:1600	arg1	growth					1602:1607	tumor growth	1596:1607	tumor growth	1596:1607	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls.
29967251	4	15	theme	in	966:967	arg1	imaging					984:990	in vivo molecular imaging	966:990	in vivo molecular imaging	966:990	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	7	16	with	cells	1293:1297	arg1	activation					1325:1334	elevated ErbB family activation	1304:1334	elevated ErbB family activation	1304:1334	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	3	17	theme	cell	826:829	arg1	profiles					851:858	glioma cell receptor expression profiles	819:858	glioma cell receptor expression profiles	819:858	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	4	18	theme	molecular	974:982	arg1	imaging					984:990	in vivo molecular imaging	966:990	in vivo molecular imaging	966:990	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	11	19	theme	oligosaccharyltransferase	1862:1886	arg1	inhibition					1888:1897	oligosaccharyltransferase inhibition	1862:1897	oligosaccharyltransferase inhibition with NGI-1	1862:1908	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	11	19	theme	oligosaccharyltransferase	1862:1886	arg1	approach					1921:1928	a novel approach	1913:1928	a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455	1913:2044	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	1	20	theme	receptor	169:176	arg1	kinase					187:192	receptor tyrosine kinase	169:192	receptor tyrosine kinase (RTK)-targeted therapies	169:217	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	1	20	theme	receptor	169:176	arg1	RTK					195:197	RTK	195:197	RTK	195:197	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	11	21	theme	malignant	1948:1956	arg1	gliomas					1958:1964	malignant gliomas	1948:1964	malignant gliomas	1948:1964	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	3	22	theme	glycosylation	661:673	arg1	state					675:679	glycosylation state	661:679	glycosylation state	661:679	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	1	23	theme	kinase	187:192	arg1	therapies					209:217	receptor tyrosine kinase (RTK)-targeted therapies	169:217	receptor tyrosine kinase (RTK)-targeted therapies	169:217	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	7	24	theme	ErbB	1313:1316	arg1	activation					1325:1334	elevated ErbB family activation	1304:1334	elevated ErbB family activation	1304:1334	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	2	25	theme	EGFR	598:601	arg1	PDGFR					626:630	PDGFR	626:630	PDGFR	626:630	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	25	theme	EGFR	598:601	arg1	FGFR1					637:641	FGFR1	637:641	FGFR1	637:641	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	25	theme	EGFR	598:601	arg1	MET					621:623	MET	621:623	MET	621:623	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	25	theme	EGFR	598:601	arg1	receptors					610:618	EGFR family receptors	598:618	EGFR family receptors	598:618	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	5	26	theme	mechanistic	995:1005	arg1	role					1007:1010	A mechanistic role	993:1010	A mechanistic role for RTK signaling	993:1028	A mechanistic role for RTK signaling was evaluated through the expression of a glycosylation-independent CD8-EGFR chimera.
29967251	7	27	theme	glioma	1286:1291	arg1	cells					1293:1297	those glioma cells	1280:1297	those glioma cells with elevated ErbB family activation	1280:1334	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	0	28	theme	Glioma	94:99	arg1	Radiosensitivity					101:116	Glioma Radiosensitivity	94:116	Glioma Radiosensitivity	94:116	Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity.
29967251	2	29	theme	therapeutic	424:434	arg1	approach					436:443	a new therapeutic approach	418:443	a new therapeutic approach for glioma radiosensitization.Experimental Design	418:493	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	0	30	theme	Oligosaccharyltransferase	0:24	arg1	Inhibition					26:35	Oligosaccharyltransferase Inhibition	0:35	Oligosaccharyltransferase Inhibition	0:35	Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity.
29967251	1	31	theme	Parallel	127:134	arg1	signaling					136:144	PURPOSE Parallel signaling	119:144	PURPOSE Parallel signaling	119:144	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	6	32	theme	protein	1153:1159	arg1	levels					1161:1166	protein levels	1153:1166	protein levels	1153:1166	RESULTS NGI-1 reduced glycosylation, protein levels, and activation of most RTKs.
29967251	6	33	gly	glycosylation	1138:1150	arg1	RTKs					1192:1195	most RTKs	1187:1195	most RTKs	1187:1195	RESULTS NGI-1 reduced glycosylation, protein levels, and activation of most RTKs.
29967251	8	34	theme	G1	1471:1472	arg1	arrest					1485:1490	G1 cell-cycle arrest	1471:1490	G1 cell-cycle arrest	1471:1490	NGI-1 radiosensitization was associated with increases in both DNA damage and G1 cell-cycle arrest.
29967251	2	35	theme	inhibitor	544:552	arg1	effects					516:522	the effects	512:522	the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1	512:641	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	3	36	from	influence	648:656	arg1	radiosensitivity					695:710	tumor cell radiosensitivity	684:710	tumor cell radiosensitivity	684:710	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	3	36	from	influence	648:656	arg1	arrest					776:781	cell-cycle arrest	765:781	cell-cycle arrest	765:781	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	3	36	from	influence	648:656	arg1	toxicity					739:746	chemotherapy-induced cell toxicity	713:746	chemotherapy-induced cell toxicity	713:746	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	3	36	from	influence	648:656	arg1	damage					753:758	DNA damage	749:758	DNA damage	749:758	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	2	37	theme	radiosensitization.Experimental	456:486	arg1	Design					488:493	glioma radiosensitization.Experimental Design	449:493	glioma radiosensitization.Experimental Design	449:493	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	7	38	theme	cytotoxic	1243:1251	arg1	effects					1253:1259	cytotoxic effects	1243:1259	cytotoxic effects	1243:1259	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	0	39	theme	Tyrosine	54:61	arg1	Kinase					63:68	Receptor Tyrosine Kinase	45:68	Receptor Tyrosine Kinase Activation	45:79	Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity.
29967251	10	40	from	effects	1675:1681	arg1	arrest					1698:1703	G1 arrest	1695:1703	G1 arrest	1695:1703	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	10	40	from	effects	1675:1681	arg1	damage					1710:1715	DNA damage	1706:1715	DNA damage	1706:1715	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	10	40	from	effects	1675:1681	arg1	radiosensitivity					1731:1746	cellular radiosensitivity	1722:1746	cellular radiosensitivity	1722:1746	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	5	41	theme	chimera	1107:1113	arg1	expression					1056:1065	the expression	1052:1065	the expression of a glycosylation-independent CD8-EGFR chimera	1052:1113	A mechanistic role for RTK signaling was evaluated through the expression of a glycosylation-independent CD8-EGFR chimera.
29967251	7	42	theme	RTK	1377:1379	arg1	activation					1381:1390	RTK activation	1377:1390	RTK activation	1377:1390	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	3	43	theme	cell	690:693	arg1	radiosensitivity					695:710	tumor cell radiosensitivity	684:710	tumor cell radiosensitivity	684:710	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	4	44	theme	tumor	895:899	arg1	growth					901:906	xenograft tumor growth	885:906	xenograft tumor growth	885:906	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	11	45	theme	related	1998:2004	arg1	commentary					2006:2015	enhanced RTK signaling.See related commentary	1971:2015	enhanced RTK signaling.See related commentary	1971:2015	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	2	46	theme	N-linked	273:280	arg1	co-					322:324	an endoplasmic reticulum co-	297:324	an endoplasmic reticulum co-	297:324	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	46	theme	N-linked	273:280	arg1	glycosylation					282:294	protein N-linked glycosylation	265:294	protein N-linked glycosylation	265:294	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	46	theme	N-linked	273:280	arg1	modification					348:359	posttranslational modification	330:359	posttranslational modification	330:359	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	4	47	theme	NGI-1	876:880	arg1	effects					865:871	The effects	861:871	The effects of NGI-1 on xenograft tumor growth	861:906	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	11	48	theme	RTK	1980:1982	arg1	commentary					2006:2015	enhanced RTK signaling.See related commentary	1971:2015	enhanced RTK signaling.See related commentary	1971:2015	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	3	49	theme	cell	734:737	arg1	toxicity					739:746	chemotherapy-induced cell toxicity	713:746	chemotherapy-induced cell toxicity	713:746	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	9	50	theme	fractionated	1538:1549	arg1	radiotherapy					1551:1562	radiotherapy	1551:1562	radiotherapy	1551:1562	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls.
29967251	5	51	theme	glycosylation-independent	1072:1096	arg1	chimera					1107:1113	a glycosylation-independent CD8-EGFR chimera	1070:1113	a glycosylation-independent CD8-EGFR chimera	1070:1113	A mechanistic role for RTK signaling was evaluated through the expression of a glycosylation-independent CD8-EGFR chimera.
29967251	6	52	theme	most	1187:1190	arg1	RTKs					1192:1195	most RTKs	1187:1195	most RTKs	1187:1195	RESULTS NGI-1 reduced glycosylation, protein levels, and activation of most RTKs.
29967251	7	53	theme	elevated	1304:1311	arg1	activation					1325:1334	elevated ErbB family activation	1304:1334	elevated ErbB family activation	1304:1334	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	10	54	theme	G1	1695:1696	arg1	arrest					1698:1703	G1 arrest	1695:1703	G1 arrest	1695:1703	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	9	55	theme	glioma	1515:1520	arg1	xenografts					1522:1531	glioma xenografts	1515:1531	glioma xenografts	1515:1531	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls.
29967251	10	56	theme	NGI-1	1686:1690	arg1	effects					1675:1681	the effects	1671:1681	the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity	1671:1746	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	2	57	theme	reticulum	312:320	arg1	co-					322:324	an endoplasmic reticulum co-	297:324	an endoplasmic reticulum co-	297:324	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	57	theme	reticulum	312:320	arg1	glycosylation					282:294	protein N-linked glycosylation	265:294	protein N-linked glycosylation	265:294	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	1	58	theme	therapies	209:217	arg1	effects					158:164	the effects	154:164	the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma	154:227	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	3	59	theme	glioma	819:824	arg1	profiles					851:858	glioma cell receptor expression profiles	819:858	glioma cell receptor expression profiles	819:858	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	2	60	theme	protein	265:271	arg1	co-					322:324	an endoplasmic reticulum co-	297:324	an endoplasmic reticulum co-	297:324	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	60	theme	protein	265:271	arg1	glycosylation					282:294	protein N-linked glycosylation	265:294	protein N-linked glycosylation	265:294	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	60	theme	protein	265:271	arg1	modification					348:359	posttranslational modification	330:359	posttranslational modification	330:359	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	61	theme	family	603:608	arg1	PDGFR					626:630	PDGFR	626:630	PDGFR	626:630	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	61	theme	family	603:608	arg1	FGFR1					637:641	FGFR1	637:641	FGFR1	637:641	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	61	theme	family	603:608	arg1	MET					621:623	MET	621:623	MET	621:623	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	61	theme	family	603:608	arg1	receptors					610:618	EGFR family receptors	598:618	EGFR family receptors	598:618	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	11	62	theme	enhanced	1971:1978	arg1	commentary					2006:2015	enhanced RTK signaling.See related commentary	1971:2015	enhanced RTK signaling.See related commentary	1971:2015	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	3	63	theme	receptor	831:838	arg1	profiles					851:858	glioma cell receptor expression profiles	819:858	glioma cell receptor expression profiles	819:858	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	3	64	theme	state	675:679	arg1	influence					648:656	The influence	644:656	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest	644:781	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	6	65	theme	RESULTS	1116:1122	arg1	NGI-1					1124:1128	RESULTS NGI-1	1116:1128	RESULTS NGI-1	1116:1128	RESULTS NGI-1 reduced glycosylation, protein levels, and activation of most RTKs.
29967251	7	66	theme	family	1318:1323	arg1	activation					1325:1334	elevated ErbB family activation	1304:1334	elevated ErbB family activation	1304:1334	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	2	67	theme	glycosylation	282:294	arg1	inhibition					251:260	inhibition	251:260	inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation,	251:402	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	4	68	from	effects	865:871	arg1	growth					901:906	xenograft tumor growth	885:906	xenograft tumor growth	885:906	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	1	69	theme	tyrosine	178:185	arg1	kinase					187:192	receptor tyrosine kinase	169:192	receptor tyrosine kinase (RTK)-targeted therapies	169:217	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	1	69	theme	tyrosine	178:185	arg1	RTK					195:197	RTK	195:197	RTK	195:197	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	2	70	theme	oligosaccharyltransferase	561:585	arg1	inhibitor					544:552	a small-molecule inhibitor	527:552	a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1)	527:593	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	8	71	theme	NGI-1	1393:1397	arg1	radiosensitization					1399:1416	NGI-1 radiosensitization	1393:1416	NGI-1 radiosensitization	1393:1416	NGI-1 radiosensitization was associated with increases in both DNA damage and G1 cell-cycle arrest.
29967251	4	72	dep	in	966:967	arg1	vivo					969:972	vivo	969:972	vivo	969:972	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	11	73	with	inhibition	1888:1897	arg1	NGI-1					1904:1908	NGI-1	1904:1908	NGI-1	1904:1908	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	2	74	from	effects	516:522	arg1	PDGFR					626:630	PDGFR	626:630	PDGFR	626:630	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	74	from	effects	516:522	arg1	FGFR1					637:641	FGFR1	637:641	FGFR1	637:641	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	74	from	effects	516:522	arg1	MET					621:623	MET	621:623	MET	621:623	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	74	from	effects	516:522	arg1	receptors					610:618	EGFR family receptors	598:618	EGFR family receptors	598:618	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	75	link	N-linked	273:280	arg1	co-					322:324	an endoplasmic reticulum co-	297:324	an endoplasmic reticulum co-	297:324	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	75	link	N-linked	273:280	arg1	glycosylation					282:294	protein N-linked glycosylation	265:294	protein N-linked glycosylation	265:294	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	2	75	link	N-linked	273:280	arg1	modification					348:359	posttranslational modification	330:359	posttranslational modification	330:359	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	11	76	theme	signaling.See	1984:1996	arg1	commentary					2006:2015	enhanced RTK signaling.See related commentary	1971:2015	enhanced RTK signaling.See related commentary	1971:2015	CONCLUSIONS This study suggests that oligosaccharyltransferase inhibition with NGI-1 is a novel approach to radiosensitize malignant gliomas with enhanced RTK signaling.See related commentary by Wahl and Lawrence, p. 455.
29967251	7	77	dep	radiosensitivity	1222:1237	arg1	the					1218:1220	the	1218:1220	the	1218:1220	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	10	78	theme	RTK	1761:1763	arg1	inhibition					1765:1774	RTK inhibition	1761:1774	RTK inhibition	1761:1774	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	10	78	theme	RTK	1761:1763	arg1	mechanism					1793:1801	the principal mechanism	1779:1801	the principal mechanism for the NGI-1 effect	1779:1822	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	7	79	theme	chemotherapy	1264:1275	arg1	radiosensitivity					1222:1237	radiosensitivity	1222:1237	radiosensitivity	1222:1237	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	7	79	theme	chemotherapy	1264:1275	arg1	effects					1253:1259	cytotoxic effects	1243:1259	cytotoxic effects	1243:1259	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	1	80	theme	PURPOSE	119:125	arg1	signaling					136:144	PURPOSE Parallel signaling	119:144	PURPOSE Parallel signaling	119:144	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	8	81	theme	DNA	1456:1458	arg1	damage					1460:1465	DNA damage	1456:1465	DNA damage	1456:1465	NGI-1 radiosensitization was associated with increases in both DNA damage and G1 cell-cycle arrest.
29967251	2	82	theme	new	420:422	arg1	approach					436:443	a new therapeutic approach	418:443	a new therapeutic approach for glioma radiosensitization.Experimental Design	418:493	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	0	83	theme	Receptor	45:52	arg1	Kinase					63:68	Receptor Tyrosine Kinase	45:68	Receptor Tyrosine Kinase Activation	45:79	Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity.
29967251	1	84	from	effects	158:164	arg1	glioma					222:227	glioma	222:227	glioma	222:227	PURPOSE Parallel signaling reduces the effects of receptor tyrosine kinase (RTK)-targeted therapies in glioma.
29967251	5	85	theme	RTK	1016:1018	arg1	signaling					1020:1028	RTK signaling	1016:1028	RTK signaling	1016:1028	A mechanistic role for RTK signaling was evaluated through the expression of a glycosylation-independent CD8-EGFR chimera.
29967251	7	86	theme	activation	1381:1390	arg1	levels					1367:1372	high levels	1362:1372	high levels of RTK activation	1362:1390	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	10	87	theme	principal	1783:1791	arg1	inhibition					1765:1774	RTK inhibition	1761:1774	RTK inhibition	1761:1774	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	10	87	theme	principal	1783:1791	arg1	mechanism					1793:1801	the principal mechanism	1779:1801	the principal mechanism for the NGI-1 effect	1779:1822	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	0	88	theme	Kinase	63:68	arg1	Activation					70:79	Receptor Tyrosine Kinase Activation	45:79	Receptor Tyrosine Kinase Activation	45:79	Oligosaccharyltransferase Inhibition Reduces Receptor Tyrosine Kinase Activation and Enhances Glioma Radiosensitivity.
29967251	5	89	theme	CD8-EGFR	1098:1105	arg1	chimera					1107:1113	a glycosylation-independent CD8-EGFR chimera	1070:1113	a glycosylation-independent CD8-EGFR chimera	1070:1113	A mechanistic role for RTK signaling was evaluated through the expression of a glycosylation-independent CD8-EGFR chimera.
29967251	2	90	theme	small-molecule	529:542	arg1	inhibitor					544:552	a small-molecule inhibitor	527:552	a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1)	527:593	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	3	91	theme	tumor	684:688	arg1	radiosensitivity					695:710	tumor cell radiosensitivity	684:710	tumor cell radiosensitivity	684:710	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	8	92	theme	cell-cycle	1474:1483	arg1	arrest					1485:1490	G1 cell-cycle arrest	1471:1490	G1 cell-cycle arrest	1471:1490	NGI-1 radiosensitization was associated with increases in both DNA damage and G1 cell-cycle arrest.
29967251	2	93	theme	glioma	449:454	arg1	Design					488:493	glioma radiosensitization.Experimental Design	449:493	glioma radiosensitization.Experimental Design	449:493	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	7	94	theme	high	1362:1365	arg1	levels					1367:1372	high levels	1362:1372	high levels of RTK activation	1362:1390	NGI-1 also enhanced the radiosensitivity and cytotoxic effects of chemotherapy in those glioma cells with elevated ErbB family activation, but not in cells without high levels of RTK activation.
29967251	4	95	theme	xenograft	885:893	arg1	growth					901:906	xenograft tumor growth	885:906	xenograft tumor growth	885:906	The effects of NGI-1 on xenograft tumor growth were tested using a nanoparticle formulation validated by in vivo molecular imaging.
29967251	9	96	with	treatment	1502:1510	arg1	radiotherapy					1551:1562	radiotherapy	1551:1562	radiotherapy	1551:1562	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls.
29967251	9	96	with	treatment	1502:1510	arg1	NGI-1					1568:1572	NGI-1	1568:1572	NGI-1	1568:1572	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls.
29967251	10	97	theme	NGI-1	1811:1815	arg1	effect					1817:1822	the NGI-1 effect	1807:1822	the NGI-1 effect	1807:1822	Expression of the CD8-EGFR eliminated the effects of NGI-1 on G1 arrest, DNA damage, and cellular radiosensitivity, identifying RTK inhibition as the principal mechanism for the NGI-1 effect.
29967251	3	98	theme	chemotherapy-induced	713:732	arg1	toxicity					739:746	chemotherapy-induced cell toxicity	713:746	chemotherapy-induced cell toxicity	713:746	The influence of glycosylation state on tumor cell radiosensitivity, chemotherapy-induced cell toxicity, DNA damage, and cell-cycle arrest were determined and correlated with glioma cell receptor expression profiles.
29967251	2	99	theme	RTK	373:375	arg1	maturation					377:386	RTK maturation	373:386	RTK maturation	373:386	We hypothesized that inhibition of protein N-linked glycosylation, an endoplasmic reticulum co- and posttranslational modification crucial for RTK maturation and activation, could provide a new therapeutic approach for glioma radiosensitization.Experimental Design: We investigated the effects of a small-molecule inhibitor of the oligosaccharyltransferase (NGI-1) on EGFR family receptors, MET, PDGFR, and FGFR1.
29967251	8	100	from	increases	1438:1446	arg1	damage					1460:1465	DNA damage	1456:1465	DNA damage	1456:1465	NGI-1 radiosensitization was associated with increases in both DNA damage and G1 cell-cycle arrest.
29967251	8	100	from	increases	1438:1446	arg1	arrest					1485:1490	G1 cell-cycle arrest	1471:1490	G1 cell-cycle arrest	1471:1490	NGI-1 radiosensitization was associated with increases in both DNA damage and G1 cell-cycle arrest.
29967251	6	101	theme	RTKs	1192:1195	arg1	glycosylation					1138:1150	glycosylation	1138:1150	glycosylation	1138:1150	RESULTS NGI-1 reduced glycosylation, protein levels, and activation of most RTKs.
29967251	6	101	theme	RTKs	1192:1195	arg1	levels					1161:1166	protein levels	1153:1166	protein levels	1153:1166	RESULTS NGI-1 reduced glycosylation, protein levels, and activation of most RTKs.
29967251	6	101	theme	RTKs	1192:1195	arg1	activation					1173:1182	activation	1173:1182	activation of most RTKs	1173:1195	RESULTS NGI-1 reduced glycosylation, protein levels, and activation of most RTKs.
29967251	9	102	theme	Combined	1493:1500	arg1	treatment					1502:1510	Combined treatment	1493:1510	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1	1493:1572	Combined treatment of glioma xenografts with fractionated radiotherapy and NGI-1 significantly reduced tumor growth compared with controls.
29305779	9	0	theme	biological	1657:1666	arg1	source					1668:1673	biological source	1657:1673	biological source	1657:1673	Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.
29305779	1	1	theme	disease	328:334	arg1	progression					299:309	the long-term progression	285:309	the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes	285:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	1	2	from	progression	299:309	arg1	diabetes					396:403	type 1 diabetes	389:403	type 1 diabetes	389:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	3	3	theme	N-linked	679:686	arg1	sugar					668:672	the unknown sugar	656:672	the unknown sugar	656:672	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	3	3	theme	N-linked	679:686	arg1	acid					699:702	a N-linked glucuronic acid	677:702	a N-linked glucuronic acid	677:702	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	1	4	theme	collagen-linked	151:165	arg1	fluorophore					172:182	a collagen-linked blue fluorophore	149:182	a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes	149:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	1	4	theme	collagen-linked	151:165	arg1	LW-1					141:144	LW-1	141:144	LW-1	141:144	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	8	5	theme	pathway	1523:1529	arg1	existence					1491:1499	the possible existence	1478:1499	the possible existence of a "glucuronidation pathway of diabetic complications	1478:1555	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	2	6	theme	NMR	467:469	arg1	analyses					471:478	earlier NMR analyses	459:478	earlier NMR analyses	459:478	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	5	7	theme	176 amu	1067:1073	arg1	loss					1059:1062	a loss	1057:1062	a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1	1057:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	4	8	theme	multiple	838:845	arg1	rounds					847:852	multiple rounds	838:852	multiple rounds of proteolytic digestion and purification	838:894	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	1	9	theme	blue	167:170	arg1	fluorophore					172:182	a collagen-linked blue fluorophore	149:182	a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes	149:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	1	9	theme	blue	167:170	arg1	LW-1					141:144	LW-1	141:144	LW-1	141:144	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	2	10	theme	advanced	574:581	arg1	end-products					593:604	advanced glycation end-products	574:604	advanced glycation end-products (AGEs)	574:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	2	10	theme	advanced	574:581	arg1	AGEs					607:610	AGEs	607:610	AGEs	607:610	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	4	11	theme	liquid	899:904	arg1	chromatography					906:919	liquid chromatography	899:919	liquid chromatography (LC)	899:924	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	4	11	theme	liquid	899:904	arg1	LC					922:923	LC	922:923	LC	922:923	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	1	12	theme	indices	340:346	arg1	progression					299:309	the long-term progression	285:309	the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes	285:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	4	13	theme	proteolytic	857:867	arg1	digestion					869:877	proteolytic digestion	857:877	proteolytic digestion	857:877	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	4	14	with	patients	804:811	arg1	diabetes/ESRD					818:830	diabetes/ESRD	818:830	diabetes/ESRD using multiple rounds of proteolytic digestion and purification	818:894	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	8	15	theme	diabetic	1534:1541	arg1	complications					1543:1555	diabetic complications	1534:1555	diabetic complications	1534:1555	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	2	16	theme	lysine	496:501	arg1	residue					503:509	a lysine residue	494:509	a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs)	494:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	3	17	theme	glucuronic	688:697	arg1	sugar					668:672	the unknown sugar	656:672	the unknown sugar	656:672	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	3	17	theme	glucuronic	688:697	arg1	acid					699:702	a N-linked glucuronic acid	677:702	a N-linked glucuronic acid	677:702	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	2	18	theme	molecule	550:557	arg1	reminiscent					559:569	a sugar molecule reminiscent	542:569	a sugar molecule reminiscent of advanced glycation end-products (AGEs)	542:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	5	19	theme	glucuronic	1135:1144	arg1	moiety					1151:1156	a glucuronic acid moiety	1133:1156	a glucuronic acid moiety in LW-1	1133:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	9	20	theme	circulating	1680:1690	arg1	aglycone					1706:1713	a circulating glucuronidine aglycone	1678:1713	a circulating glucuronidine aglycone	1678:1713	Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.
29305779	1	21	theme	subclinical	351:361	arg1	disease					378:384	subclinical cardiovascular disease	351:384	subclinical cardiovascular disease	351:384	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	5	22	from	LW-1	1161:1164	arg1	presence					1121:1128	the presence	1117:1128	the presence of a glucuronic acid moiety in LW-1	1117:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	3	23	link	N-linked	679:686	arg1	sugar					668:672	the unknown sugar	656:672	the unknown sugar	656:672	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	3	23	link	N-linked	679:686	arg1	acid					699:702	a N-linked glucuronic acid	677:702	a N-linked glucuronic acid	677:702	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	0	24	theme	long-term	104:112	arg1	complications					114:126	the long-term complications	100:126	the long-term complications of diabetes	100:138	Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.
29305779	1	25	theme	cardiovascular	363:376	arg1	disease					378:384	subclinical cardiovascular disease	351:384	subclinical cardiovascular disease	351:384	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	2	26	theme	earlier	459:465	arg1	analyses					471:478	earlier NMR analyses	459:478	earlier NMR analyses	459:478	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	7	27	theme	parent	1360:1365	arg1	molecule					1367:1374	the parent molecule	1356:1374	the parent molecule	1356:1374	Only glucuronidase could cleave the sugar from the parent molecule.
29305779	9	28	theme	aglycone	1706:1713	arg1	origin					1646:1651	molecular origin	1636:1651	molecular origin	1636:1651	Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.
29305779	9	28	theme	aglycone	1706:1713	arg1	source					1668:1673	biological source	1657:1673	biological source	1657:1673	Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.
29305779	1	29	theme	disease	378:384	arg1	indices					340:346	indices	340:346	indices of subclinical cardiovascular disease	340:384	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	1	29	theme	disease	378:384	arg1	disease					328:334	microvascular disease	314:334	microvascular disease	314:334	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	2	30	theme	end-products	593:604	arg1	reminiscent					559:569	a sugar molecule reminiscent	542:569	a sugar molecule reminiscent of advanced glycation end-products (AGEs)	542:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	4	31	theme	digestion	869:877	arg1	rounds					847:852	multiple rounds	838:852	multiple rounds of proteolytic digestion and purification	838:894	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	1	32	theme	skin	190:193	arg1	levels					195:200	levels	195:200	levels	195:200	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	2	33	theme	glycation	583:591	arg1	end-products					593:604	advanced glycation end-products	574:604	advanced glycation end-products (AGEs)	574:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	2	33	theme	glycation	583:591	arg1	AGEs					607:610	AGEs	607:610	AGEs	607:610	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	7	34	from	molecule	1367:1374	arg1	sugar					1345:1349	the sugar	1341:1349	the sugar from the parent molecule	1341:1374	Only glucuronidase could cleave the sugar from the parent molecule.
29305779	5	35	theme	LC-mass	1022:1028	arg1	MS					1044:1045	MS	1044:1045	MS	1044:1045	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	35	theme	LC-mass	1022:1028	arg1	spectrometry					1030:1041	LC-mass spectrometry	1022:1041	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS)	927:1046	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	2	36	theme	LW-1	432:435	arg1	elusive					446:452	elusive	446:452	elusive	446:452	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	2	36	theme	LW-1	432:435	arg1	structure					419:427	The chemical structure	406:427	The chemical structure of LW-1	406:435	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	8	37	dep	establish	1391:1399	arg1	raise					1472:1476	raise	1472:1476	raise the possible existence of a "glucuronidation pathway of diabetic complications"	1472:1556	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	8	37	dep	establish	1391:1399	arg1	named					1428:1432	named	1428:1432	named glucuronidine	1428:1446	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	0	38	theme	diabetes	131:138	arg1	complications					114:126	the long-term complications	100:126	the long-term complications of diabetes	100:138	Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.
29305779	5	39	theme	Advanced	927:934	arg1	techniques					940:949	Advanced NMR techniques	927:949	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS)	927:1046	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	6	40	dep	β-glycosidases	1213:1226	arg1	glucuronidase					1257:1269	glucuronidase	1257:1269	glucuronidase	1257:1269	To confirm this data, LW-1 was incubated with β-glycosidases (glucosidase, galactosidase, glucuronidase) and products were analyzed by LC-MS.
29305779	6	40	dep	β-glycosidases	1213:1226	arg1	galactosidase					1242:1254	galactosidase	1242:1254	galactosidase	1242:1254	To confirm this data, LW-1 was incubated with β-glycosidases (glucosidase, galactosidase, glucuronidase) and products were analyzed by LC-MS.
29305779	6	40	dep	β-glycosidases	1213:1226	arg1	glucosidase					1229:1239	glucosidase	1229:1239	glucosidase	1229:1239	To confirm this data, LW-1 was incubated with β-glycosidases (glucosidase, galactosidase, glucuronidase) and products were analyzed by LC-MS.
29305779	5	41	dep	loss	1059:1062	arg1	point					1108:1112	point	1108:1112	point to the presence of a glucuronic acid moiety in LW-1	1108:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	2	42	theme	aromatic	517:524	arg1	ring					526:529	an aromatic ring	514:529	an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs)	514:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	5	43	theme	NMR	936:938	arg1	techniques					940:949	Advanced NMR techniques	927:949	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS)	927:1046	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	8	44	theme	first	1461:1465	arg1	time					1467:1470	the first time	1457:1470	the first time	1457:1470	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	2	45	theme	chemical	410:417	arg1	elusive					446:452	elusive	446:452	elusive	446:452	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	2	45	theme	chemical	410:417	arg1	structure					419:427	The chemical structure	406:427	The chemical structure of LW-1	406:435	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	0	46	theme	product	45:51	arg1	LW-1					53:56	the glycation product LW-1	31:56	the glycation product LW-1	31:56	Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.
29305779	8	47	theme	glucuronidation	1507:1521	arg1	pathway					1523:1529	a "glucuronidation pathway	1504:1529	a "glucuronidation pathway of diabetic complications	1504:1555	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	5	48	from	presence	1121:1128	arg1	LW-1					1161:1164	LW-1	1161:1164	LW-1	1161:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	1	49	theme	type	389:392	arg1	diabetes					396:403	type 1 diabetes	389:403	type 1 diabetes	389:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	0	50	theme	glycation	35:43	arg1	LW-1					53:56	the glycation product LW-1	31:56	the glycation product LW-1	31:56	Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.
29305779	5	51	theme	atomic	1076:1081	arg1	unit					1088:1091	atomic mass unit	1076:1091	atomic mass unit	1076:1091	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	51	theme	atomic	1076:1081	arg1	176 amu					1067:1073	176 amu	1067:1073	176 amu (atomic mass unit)	1067:1092	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	52	dep	together	1008:1015	arg1	with					1017:1020	with	1017:1020	with	1017:1020	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	9	53	theme	Future	1559:1564	arg1	research					1566:1573	Future research	1559:1573	Future research	1559:1573	Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.
29305779	5	54	theme	1H-1H	982:986	arg1	1H-NMR					952:957	1H-NMR	952:957	1H-NMR	952:957	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	54	theme	1H-1H	982:986	arg1	TOCSY					988:992	1H-1H TOCSY	982:992	1H-1H TOCSY	982:992	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	55	from	moiety	1151:1156	arg1	LW-1					1161:1164	LW-1	1161:1164	LW-1	1161:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	9	56	theme	molecular	1636:1644	arg1	origin					1646:1651	molecular origin	1636:1651	molecular origin	1636:1651	Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.
29305779	1	57	theme	long-term	289:297	arg1	progression					299:309	the long-term progression	285:309	the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes	285:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	2	58	theme	sugar	544:548	arg1	reminiscent					559:569	a sugar molecule reminiscent	542:569	a sugar molecule reminiscent of advanced glycation end-products (AGEs)	542:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	3	59	theme	unknown	660:666	arg1	sugar					668:672	the unknown sugar	656:672	the unknown sugar	656:672	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	3	59	theme	unknown	660:666	arg1	acid					699:702	a N-linked glucuronic acid	677:702	a N-linked glucuronic acid	677:702	We hypothesized and demonstrate here that the unknown sugar is a N-linked glucuronic acid.
29305779	8	60	theme	possible	1482:1489	arg1	existence					1491:1499	the possible existence	1478:1499	the possible existence of a "glucuronidation pathway of diabetic complications	1478:1555	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	1	61	link	collagen-linked	151:165	arg1	fluorophore					172:182	a collagen-linked blue fluorophore	149:182	a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes	149:403	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	1	61	link	collagen-linked	151:165	arg1	LW-1					141:144	LW-1	141:144	LW-1	141:144	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	5	62	theme	1H-13C	995:1000	arg1	1H-NMR					952:957	1H-NMR	952:957	1H-NMR	952:957	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	62	theme	1H-13C	995:1000	arg1	HMBC					1002:1005	1H-13C HMBC	995:1005	1H-13C HMBC	995:1005	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	7	63	theme	Only	1309:1312	arg1	glucuronidase					1314:1326	Only glucuronidase	1309:1326	Only glucuronidase	1309:1326	Only glucuronidase could cleave the sugar from the parent molecule.
29305779	9	64	theme	glucuronidine	1692:1704	arg1	aglycone					1706:1713	a circulating glucuronidine aglycone	1678:1713	a circulating glucuronidine aglycone	1678:1713	Future research is needed to rigorously probe this concept and elucidate the molecular origin and biological source of a circulating glucuronidine aglycone.
29305779	4	65	theme	skin	765:768	arg1	collagen					770:777	~99 g insoluble skin collagen	749:777	~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC)	749:924	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	2	66	dep	it	487:488	arg1	has					490:492	has	490:492	has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs)	490:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	4	67	theme	insoluble	755:763	arg1	collagen					770:777	~99 g insoluble skin collagen	749:777	~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC)	749:924	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	5	68	dep	techniques	940:949	arg1	TOCSY					988:992	1H-1H TOCSY	982:992	1H-1H TOCSY	982:992	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	68	dep	techniques	940:949	arg1	13C-NMR					960:966	13C-NMR	960:966	13C-NMR	960:966	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	68	dep	techniques	940:949	arg1	HSQC					976:979	1H-13C HSQC	969:979	1H-13C HSQC	969:979	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	68	dep	techniques	940:949	arg1	1H-NMR					952:957	1H-NMR	952:957	1H-NMR	952:957	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	68	dep	techniques	940:949	arg1	HMBC					1002:1005	1H-13C HMBC	995:1005	1H-13C HMBC	995:1005	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	8	69	theme	complications	1543:1555	arg1	pathway					1523:1529	a "glucuronidation pathway	1504:1529	a "glucuronidation pathway of diabetic complications	1504:1555	These results establish LW-1 as a glucuronide, now named glucuronidine, and for the first time raise the possible existence of a "glucuronidation pathway of diabetic complications".
29305779	5	70	theme	acid	1146:1149	arg1	moiety					1151:1156	a glucuronic acid moiety	1133:1156	a glucuronic acid moiety in LW-1	1133:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	4	71	theme	purification	883:894	arg1	rounds					847:852	multiple rounds	838:852	multiple rounds of proteolytic digestion and purification	838:894	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	2	72	from	residue	503:509	arg1	ring					526:529	an aromatic ring	514:529	an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs)	514:611	The chemical structure of LW-1 is still elusive, but earlier NMR analyses showed it has a lysine residue in an aromatic ring coupled to a sugar molecule reminiscent of advanced glycation end-products (AGEs).
29305779	4	73	theme	~99 g	749:753	arg1	collagen					770:777	~99 g insoluble skin collagen	749:777	~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC)	749:924	LW-1 was extracted and highly purified from ~99 g insoluble skin collagen obtained at autopsy from patients with diabetes/ESRD using multiple rounds of proteolytic digestion and purification by liquid chromatography (LC).
29305779	5	74	theme	moiety	1151:1156	arg1	presence					1121:1128	the presence	1117:1128	the presence of a glucuronic acid moiety in LW-1	1117:1164	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	75	theme	mass	1083:1086	arg1	unit					1088:1091	atomic mass unit	1076:1091	atomic mass unit	1076:1091	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	75	theme	mass	1083:1086	arg1	176 amu					1067:1073	176 amu	1067:1073	176 amu (atomic mass unit)	1067:1092	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	76	theme	1H-13C	969:974	arg1	HSQC					976:979	1H-13C HSQC	969:979	1H-13C HSQC	969:979	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	5	76	theme	1H-13C	969:974	arg1	1H-NMR					952:957	1H-NMR	952:957	1H-NMR	952:957	Advanced NMR techniques (1H-NMR, 13C-NMR, 1H-13C HSQC, 1H-1H TOCSY, 1H-13C HMBC) together with LC-mass spectrometry (MS) revealed a loss of 176 amu (atomic mass unit) unequivocally point to the presence of a glucuronic acid moiety in LW-1.
29305779	1	77	theme	end-stage	234:242	arg1	ESRD					259:262	ESRD	259:262	ESRD	259:262	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	1	77	theme	end-stage	234:242	arg1	disease					250:256	end-stage renal disease	234:256	end-stage renal disease (ESRD)	234:263	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	0	78	theme	tentative	59:67	arg1	structure					69:77	tentative structure	59:77	tentative structure	59:77	Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.
29305779	1	79	theme	microvascular	314:326	arg1	disease					328:334	microvascular disease	314:334	microvascular disease	314:334	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	0	80	dep	Evidence	0:7	arg1	implications					83:94	implications	83:94	implications for the long-term complications of diabetes	83:138	Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.
29305779	0	80	dep	Evidence	0:7	arg1	structure					69:77	tentative structure	59:77	tentative structure	59:77	Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.
29305779	1	81	theme	renal	244:248	arg1	ESRD					259:262	ESRD	259:262	ESRD	259:262	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29305779	1	81	theme	renal	244:248	arg1	disease					250:256	end-stage renal disease	234:256	end-stage renal disease (ESRD)	234:263	LW-1 is a collagen-linked blue fluorophore whose skin levels increase with age, diabetes and end-stage renal disease (ESRD), and correlate with the long-term progression of microvascular disease and indices of subclinical cardiovascular disease in type 1 diabetes.
29093093	4	0	gly	glycoprotein	654:665	arg1	glycoprotein					654:665	the S glycoprotein trimer	648:672	the S glycoprotein trimer	648:672	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	7	1	theme	intestine	1519:1527	arg1	environment					1494:1504	the protease-rich environment	1476:1504	the protease-rich environment of the small intestine	1476:1527	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	2	theme	S	2386:2386	arg1	glycoproteins					2388:2400	most other characterized coronavirus S glycoproteins	2349:2400	most other characterized coronavirus S glycoproteins	2349:2400	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	8	3	theme	devastating	1953:1963	arg1	consequences					1965:1976	devastating consequences	1953:1976	devastating consequences for the swine industry worldwide	1953:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	4	4	theme	glycoprotein	654:665	arg1	trimer					667:672	the S glycoprotein trimer	648:672	the S glycoprotein trimer	648:672	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	9	5	theme	human	2251:2255	arg1	coronavirus					2269:2279	a human respiratory coronavirus	2249:2279	a human respiratory coronavirus	2249:2279	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	2	6	theme	S	285:285	arg1	glycoprotein					288:299	the spike (S) glycoprotein	274:299	the spike (S) glycoprotein anchored in the viral envelope	274:330	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	8	7	theme	cryo-electron	1807:1819	arg1	microscopy					1821:1830	near-atomic-resolution cryo-electron microscopy	1784:1830	a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide	1782:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	1	8	theme	severe	189:194	arg1	syndrome					214:221	severe acute respiratory syndrome	189:221	severe acute respiratory syndrome	189:221	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	7	9	theme	PDCoV	1446:1450	arg1	protein					1422:1428	the S protein	1416:1428	the S protein of enterotropic PDCoV	1416:1450	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	8	10	theme	swine	1986:1990	arg1	worldwide					2001:2009	the swine industry worldwide	1982:2009	the swine industry worldwide	1982:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	2	11	theme	viral	317:321	arg1	envelope					323:330	the viral envelope	313:330	the viral envelope	313:330	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	1	12	theme	respiratory	202:212	arg1	syndrome					214:221	severe acute respiratory syndrome	189:221	severe acute respiratory syndrome	189:221	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	10	13	theme	fine-tune	2458:2466	arg1	activation					2475:2484	fine-tune fusion activation	2458:2484	fine-tune fusion activation	2458:2484	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	6	14	theme	activation	1170:1179	arg1	loop					1181:1184	a shortened S2' activation loop	1154:1184	a shortened S2' activation loop	1154:1184	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	3	15	theme	host	544:547	arg1	response					564:571	the host humoral immune response	540:571	the host humoral immune response	540:571	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	7	16	theme	S	1420:1420	arg1	protein					1422:1428	the S protein	1416:1428	the S protein of enterotropic PDCoV	1416:1450	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	2	17	theme	viral	377:381	arg1	membranes					396:404	the viral and cellular membranes	373:404	the viral and cellular membranes	373:404	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	5	18	theme	respective	1106:1115	arg1	hosts					1117:1121	their respective hosts	1100:1121	their respective hosts	1100:1121	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	8	19	theme	ectodomain	1851:1860	arg1	trimer					1862:1867	the S ectodomain trimer	1845:1867	the S ectodomain trimer	1845:1867	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	5	20	theme	S	864:864	arg1	glycans					847:853	the glycans	843:853	the glycans of PDCoV S	843:864	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	6	21	theme	acids	1230:1234	arg1	number					1208:1213	a reduced number	1198:1213	a reduced number of basic amino acids	1198:1234	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	5	22	theme	immune	1081:1086	arg1	pressure					1088:1095	comparable immune pressure	1070:1095	comparable immune pressure in their respective hosts	1070:1121	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	2	23	theme	spike	278:282	arg1	glycoprotein					288:299	the spike (S) glycoprotein	274:299	the spike (S) glycoprotein anchored in the viral envelope	274:330	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	8	24	theme	pathogenic	1878:1887	arg1	responsible					1905:1915	responsible	1905:1915	responsible	1905:1915	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	8	24	theme	pathogenic	1878:1887	arg1	PDCoV					1889:1893	the pathogenic PDCoV	1874:1893	the pathogenic PDCoV	1874:1893	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	1	25	theme	major	146:150	arg1	pathogens					158:166	major human pathogens	146:166	major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome	146:258	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	7	26	theme	S	1670:1670	arg1	glycoprotein					1672:1683	transmembrane S glycoprotein	1656:1683	transmembrane S glycoprotein trimers	1656:1691	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	7	27	theme	S	1387:1387	arg1	proteins					1389:1396	recently characterized betacoronavirus S proteins	1348:1396	recently characterized betacoronavirus S proteins	1348:1396	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	4	28	theme	pathogenic	683:692	arg1	PDCoV					720:724	PDCoV	720:724	PDCoV	720:724	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	4	28	theme	pathogenic	683:692	arg1	deltacoronavirus					702:717	the pathogenic porcine deltacoronavirus	679:717	the pathogenic porcine deltacoronavirus (PDCoV)	679:725	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	5	29	from	pressure	1088:1095	arg1	hosts					1117:1121	their respective hosts	1100:1121	their respective hosts	1100:1121	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	5	30	theme	respiratory	918:928	arg1	S					947:947	the human respiratory coronavirus NL63 S	908:947	the human respiratory coronavirus NL63 S	908:947	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	7	31	theme	infectivity.IMPORTANCE	1615:1636	arg1	Coronaviruses					1638:1650	infectivity.IMPORTANCE Coronaviruses	1615:1650	infectivity.IMPORTANCE Coronaviruses	1615:1650	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	32	theme	infected	2545:2552	arg1	hosts					2554:2558	infected hosts	2545:2558	infected hosts	2545:2558	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	4	33	theme	identified	758:767	arg1	genus					786:790	the recently identified Deltacoronavirus genus	745:790	the recently identified Deltacoronavirus genus	745:790	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	0	34	theme	Enteric	92:98	arg1	Infections					100:109	Enteric Infections	92:109	Enteric Infections	92:109	Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections.
29093093	10	35	theme	intestine	2532:2540	arg1	environment					2507:2517	the protease-rich environment	2489:2517	the protease-rich environment of the small intestine of infected hosts	2489:2558	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	2	36	theme	membranes	396:404	arg1	fusion					363:368	fusion	363:368	fusion	363:368	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	2	36	theme	membranes	396:404	arg1	attachment					348:357	host attachment	343:357	host attachment	343:357	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	7	37	theme	cellular	1748:1755	arg1	membranes					1757:1765	the viral and cellular membranes	1734:1765	the viral and cellular membranes	1734:1765	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	7	38	theme	betacoronavirus	1371:1385	arg1	proteins					1389:1396	recently characterized betacoronavirus S proteins	1348:1396	recently characterized betacoronavirus S proteins	1348:1396	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	39	theme	other	2354:2358	arg1	glycoproteins					2388:2400	most other characterized coronavirus S glycoproteins	2349:2400	most other characterized coronavirus S glycoproteins	2349:2400	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	7	40	theme	viral	1738:1742	arg1	membranes					1757:1765	the viral and cellular membranes	1734:1765	the viral and cellular membranes	1734:1765	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	6	41	theme	basic	1218:1222	arg1	acids					1230:1234	basic amino acids	1218:1234	basic amino acids	1218:1234	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	7	42	theme	premature	1577:1585	arg1	triggering					1587:1596	premature triggering	1577:1596	premature triggering	1577:1596	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	5	43	theme	surface	971:977	arg1	areas					979:983	similar surface areas	963:983	similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts	963:1121	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	5	44	theme	Structural	793:802	arg1	data					824:827	Structural and glycoproteomics data	793:827	Structural and glycoproteomics data	793:827	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	0	45	theme	Spike	58:62	arg1	Glycoprotein					64:75	a Deltacoronavirus Spike Glycoprotein	39:75	a Deltacoronavirus Spike Glycoprotein	39:75	Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections.
29093093	3	46	theme	potential	482:490	arg1	target					530:535	the main target	521:535	the main target of the host humoral immune response	521:571	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	3	46	theme	potential	482:490	arg1	protein					435:441	The S protein	429:441	The S protein	429:441	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	3	46	theme	potential	482:490	arg1	determinant					454:464	a major determinant	446:464	a major determinant of the zoonotic potential of coronaviruses	446:507	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	5	47	theme	glycoproteomics	808:822	arg1	data					824:827	Structural and glycoproteomics data	793:827	Structural and glycoproteomics data	793:827	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	7	48	theme	fusion	1550:1555	arg1	activation					1557:1566	its fusion activation	1546:1566	its fusion activation	1546:1566	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	6	49	theme	shortened	1156:1164	arg1	loop					1181:1184	a shortened S2' activation loop	1154:1184	a shortened S2' activation loop	1154:1184	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	9	50	theme	reminiscent	2197:2207	arg1	way					2193:2195	a way	2191:2195	a way reminiscent of what has recently been described for a human respiratory coronavirus	2191:2279	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	1	51	theme	respiratory	239:249	arg1	syndrome					251:258	Middle East respiratory syndrome	227:258	Middle East respiratory syndrome	227:258	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	3	52	theme	main	525:528	arg1	target					530:535	the main target	521:535	the main target of the host humoral immune response	521:571	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	4	53	theme	3.5-Å-resolution	593:608	arg1	microscopy					624:633	3.5-Å-resolution cryo-electron microscopy	593:633	the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus	589:790	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	3	54	theme	coronaviruses	495:507	arg1	potential					482:490	the zoonotic potential	469:490	the zoonotic potential of coronaviruses	469:507	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	7	55	theme	small	1513:1517	arg1	intestine					1519:1527	the small intestine	1509:1527	the small intestine	1509:1527	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	2	56	gly	glycoprotein	288:299	arg1	glycoprotein					288:299	the spike (S) glycoprotein	274:299	the spike (S) glycoprotein anchored in the viral envelope	274:330	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	10	57	theme	coronavirus	2374:2384	arg1	glycoproteins					2388:2400	most other characterized coronavirus S glycoproteins	2349:2400	most other characterized coronavirus S glycoproteins	2349:2400	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	6	58	theme	reduced	1200:1206	arg1	number					1208:1213	a reduced number	1198:1213	a reduced number of basic amino acids	1198:1234	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	7	59	theme	protease-rich	1480:1492	arg1	environment					1494:1504	the protease-rich environment	1476:1504	the protease-rich environment of the small intestine	1476:1527	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	60	theme	enteric	2420:2426	arg1	coronaviruses					2428:2440	enteric coronaviruses	2420:2440	enteric coronaviruses	2420:2440	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	9	61	theme	Structural	2012:2021	arg1	data					2043:2046	Structural and glycoproteomics data	2012:2046	Structural and glycoproteomics data	2012:2046	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	4	62	theme	S	652:652	arg1	trimer					667:672	the S glycoprotein trimer	648:672	the S glycoprotein trimer	648:672	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	9	63	theme	respiratory	2257:2267	arg1	coronavirus					2269:2279	a human respiratory coronavirus	2249:2279	a human respiratory coronavirus	2249:2279	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	8	64	theme	industry	1992:1999	arg1	worldwide					2001:2009	the swine industry worldwide	1982:2009	the swine industry worldwide	1982:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	3	65	theme	humoral	549:555	arg1	response					564:571	the host humoral immune response	540:571	the host humoral immune response	540:571	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	8	66	theme	near-atomic-resolution	1784:1805	arg1	microscopy					1821:1830	near-atomic-resolution cryo-electron microscopy	1784:1830	a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide	1782:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	1	67	theme	acute	196:200	arg1	syndrome					214:221	severe acute respiratory syndrome	189:221	severe acute respiratory syndrome	189:221	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	9	68	link	N-linked	2089:2096	arg1	glycans					2098:2104	78 N-linked glycans	2086:2104	78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus	2086:2279	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	9	69	theme	glycoproteomics	2027:2041	arg1	data					2043:2046	Structural and glycoproteomics data	2012:2046	Structural and glycoproteomics data	2012:2046	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	4	70	theme	trimer	667:672	arg1	structure					635:643	the 3.5-Å-resolution cryo-electron microscopy structure	589:643	the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus	589:790	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	8	71	theme	microscopy	1821:1830	arg1	structure					1832:1840	a near-atomic-resolution cryo-electron microscopy structure	1782:1840	a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide	1782:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	1	72	theme	syndrome	214:221	arg1	outbreaks					176:184	outbreaks	176:184	outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome	176:258	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	3	73	theme	immune	557:562	arg1	response					564:571	the host humoral immune response	540:571	the host humoral immune response	540:571	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	7	74	theme	host	1704:1707	arg1	attachment					1709:1718	host attachment	1704:1718	host attachment	1704:1718	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	7	75	theme	enterotropic	1433:1444	arg1	PDCoV					1446:1450	enterotropic PDCoV	1433:1450	enterotropic PDCoV	1433:1450	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	4	76	theme	microscopy	624:633	arg1	structure					635:643	the 3.5-Å-resolution cryo-electron microscopy structure	589:643	the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus	589:790	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	5	77	theme	PDCoV	858:862	arg1	S					864:864	PDCoV S	858:864	PDCoV S	858:864	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	9	78	theme	PDCoV	2060:2064	arg1	S					2066:2066	PDCoV S	2060:2066	PDCoV S	2060:2066	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	3	79	theme	response	564:571	arg1	target					530:535	the main target	521:535	the main target of the host humoral immune response	521:571	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	3	79	theme	response	564:571	arg1	protein					435:441	The S protein	429:441	The S protein	429:441	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	3	79	theme	response	564:571	arg1	determinant					454:464	a major determinant	446:464	a major determinant of the zoonotic potential of coronaviruses	446:507	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	8	80	theme	S	1849:1849	arg1	trimer					1862:1867	the S ectodomain trimer	1845:1867	the S ectodomain trimer	1845:1867	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	5	81	theme	coronavirus	930:940	arg1	S					947:947	the human respiratory coronavirus NL63 S	908:947	the human respiratory coronavirus NL63 S	908:947	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	7	82	theme	glycoprotein	1672:1683	arg1	trimers					1685:1691	transmembrane S glycoprotein trimers	1656:1691	transmembrane S glycoprotein trimers	1656:1691	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	8	83	contain	had	1949:1951	arg1	responsible					1905:1915	responsible	1905:1915	responsible	1905:1915	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	8	83	contain	had	1949:1951	arg2	consequences					1965:1976	devastating consequences	1953:1976	devastating consequences for the swine industry worldwide	1953:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	8	83	contain	had	1949:1951	arg1	PDCoV					1889:1893	the pathogenic PDCoV	1874:1893	the pathogenic PDCoV	1874:1893	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	5	84	theme	comparable	1070:1079	arg1	pressure					1088:1095	comparable immune pressure	1070:1095	comparable immune pressure in their respective hosts	1070:1121	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	8	85	theme	trimer	1862:1867	arg1	structure					1832:1840	a near-atomic-resolution cryo-electron microscopy structure	1782:1840	a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide	1782:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	7	86	theme	transmembrane	1656:1668	arg1	glycoprotein					1672:1683	transmembrane S glycoprotein	1656:1683	transmembrane S glycoprotein trimers	1656:1691	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	87	theme	fusion	2468:2473	arg1	activation					2475:2484	fine-tune fusion activation	2458:2484	fine-tune fusion activation	2458:2484	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	6	88	theme	amino	1224:1228	arg1	acids					1230:1234	basic amino acids	1218:1234	basic amino acids	1218:1234	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	0	89	theme	Glycoprotein	64:75	arg1	Shield					7:12	Shield	7:12	Shield	7:12	Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections.
29093093	1	90	theme	human	152:156	arg1	pathogens					158:166	major human pathogens	146:166	major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome	146:258	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	7	91	theme	Coronaviruses	1638:1650	arg1	reduction					1602:1610	reduction	1602:1610	reduction of infectivity.IMPORTANCE Coronaviruses	1602:1650	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	9	92	theme	N-linked	2089:2096	arg1	glycans					2098:2104	78 N-linked glycans	2086:2104	78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus	2086:2279	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	10	93	gly	glycoproteins	2388:2400	arg1	glycoproteins					2388:2400	most other characterized coronavirus S glycoproteins	2349:2400	most other characterized coronavirus S glycoproteins	2349:2400	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	5	94	theme	human	912:916	arg1	S					947:947	the human respiratory coronavirus NL63 S	908:947	the human respiratory coronavirus NL63 S	908:947	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	10	95	theme	protease-rich	2493:2505	arg1	environment					2507:2517	the protease-rich environment	2489:2517	the protease-rich environment of the small intestine of infected hosts	2489:2558	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	4	96	theme	porcine	694:700	arg1	PDCoV					720:724	PDCoV	720:724	PDCoV	720:724	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	4	96	theme	porcine	694:700	arg1	deltacoronavirus					702:717	the pathogenic porcine deltacoronavirus	679:717	the pathogenic porcine deltacoronavirus (PDCoV)	679:725	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	8	97	from	diarrhea	1921:1928	arg1	piglets					1933:1939	piglets	1933:1939	piglets	1933:1939	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	9	98	theme	protein	2122:2128	arg1	surface					2130:2136	the protein surface	2118:2136	the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus	2118:2279	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	8	99	from	PDCoV	1889:1893	arg1	structure					1832:1840	a near-atomic-resolution cryo-electron microscopy structure	1782:1840	a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide	1782:2009	We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide.
29093093	7	100	theme	characterized	1357:1369	arg1	proteins					1389:1396	recently characterized betacoronavirus S proteins	1348:1396	recently characterized betacoronavirus S proteins	1348:1396	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	101	theme	small	2526:2530	arg1	intestine					2532:2540	the small intestine	2522:2540	the small intestine of infected hosts	2522:2558	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	10	102	theme	characterized	2360:2372	arg1	glycoproteins					2388:2400	most other characterized coronavirus S glycoproteins	2349:2400	most other characterized coronavirus S glycoproteins	2349:2400	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	4	103	theme	Deltacoronavirus	769:784	arg1	genus					786:790	the recently identified Deltacoronavirus genus	745:790	the recently identified Deltacoronavirus genus	745:790	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	2	104	theme	cellular	387:394	arg1	membranes					396:404	the viral and cellular membranes	373:404	the viral and cellular membranes	373:404	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	7	105	theme	membranes	1757:1765	arg1	attachment					1709:1718	host attachment	1704:1718	host attachment	1704:1718	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	7	105	theme	membranes	1757:1765	arg1	fusion					1724:1729	fusion	1724:1729	fusion	1724:1729	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	106	theme	most	2349:2352	arg1	glycoproteins					2388:2400	most other characterized coronavirus S glycoproteins	2349:2400	most other characterized coronavirus S glycoproteins	2349:2400	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	3	107	theme	S	433:433	arg1	protein					435:441	The S protein	429:441	The S protein	429:441	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	3	107	theme	S	433:433	arg1	determinant					454:464	a major determinant	446:464	a major determinant of the zoonotic potential of coronaviruses	446:507	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	0	108	theme	Fusion	18:23	arg1	Activation					25:34	Glycan Shield and Fusion Activation	0:34	Activation	25:34	Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections.
29093093	5	109	theme	similar	963:969	arg1	areas					979:983	similar surface areas	963:983	similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts	963:1121	Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts.
29093093	7	110	theme	PDCoV	1335:1339	arg1	S					1341:1341	PDCoV S	1335:1341	PDCoV S	1335:1341	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	10	111	theme	hosts	2554:2558	arg1	intestine					2532:2540	the small intestine	2522:2540	the small intestine of infected hosts	2522:2558	PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.
29093093	9	112	theme	neutralizing	2164:2175	arg1	antibodies					2177:2186	neutralizing antibodies	2164:2186	neutralizing antibodies	2164:2186	Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus.
29093093	1	113	theme	Middle	227:232	arg1	syndrome					251:258	Middle East respiratory syndrome	227:258	Middle East respiratory syndrome	227:258	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	3	114	theme	major	448:452	arg1	protein					435:441	The S protein	429:441	The S protein	429:441	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	3	114	theme	major	448:452	arg1	determinant					454:464	a major determinant	446:464	a major determinant of the zoonotic potential of coronaviruses	446:507	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	0	115	theme	Deltacoronavirus	41:56	arg1	Glycoprotein					64:75	a Deltacoronavirus Spike Glycoprotein	39:75	a Deltacoronavirus Spike Glycoprotein	39:75	Glycan Shield and Fusion Activation of a Deltacoronavirus Spike Glycoprotein Fine-Tuned for Enteric Infections.
29093093	6	116	theme	S2	1166:1167	arg1	loop					1181:1184	a shortened S2' activation loop	1154:1184	a shortened S2' activation loop	1154:1184	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	2	117	theme	host	343:346	arg1	attachment					348:357	host attachment	343:357	host attachment	343:357	They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection.
29093093	7	118	gly	glycoprotein	1672:1683	arg1	glycoprotein					1672:1683	transmembrane S glycoprotein	1656:1683	transmembrane S glycoprotein trimers	1656:1691	This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes.
29093093	6	119	contain	containing	1187:1196	arg1	loop					1181:1184	a shortened S2' activation loop	1154:1184	a shortened S2' activation loop	1154:1184	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	6	119	contain	containing	1187:1196	arg2	number					1208:1213	a reduced number	1198:1213	a reduced number of basic amino acids	1198:1234	The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant.
29093093	3	120	theme	zoonotic	473:480	arg1	potential					482:490	the zoonotic potential	469:490	the zoonotic potential of coronaviruses	469:507	The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response.
29093093	1	121	theme	syndrome	251:258	arg1	outbreaks					176:184	outbreaks	176:184	outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome	176:258	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	1	122	theme	East	234:237	arg1	syndrome					251:258	Middle East respiratory syndrome	227:258	Middle East respiratory syndrome	227:258	Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome.
29093093	4	123	theme	cryo-electron	610:622	arg1	microscopy					624:633	3.5-Å-resolution cryo-electron microscopy	593:633	the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus	589:790	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
29093093	4	124	from	deltacoronavirus	702:717	arg1	structure					635:643	the 3.5-Å-resolution cryo-electron microscopy structure	589:643	the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus	589:790	We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus.
27984695	7	0	theme	[14C	1477:1480	arg1	PhIP					1482:1485	the [14C]PhIP	1473:1485	the [14C]PhIP	1473:1485	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	6	1	theme	digestion	1131:1139	arg1	treatment					1068:1076	Mild acid treatment	1058:1076	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h]	1058:1215	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	9	2	theme	acid-labile	1856:1866	arg1	adduct					1880:1885	an acid-labile sulfinamide adduct	1853:1885	an acid-labile sulfinamide adduct formed at the Cys34 residue	1853:1913	These findings suggest that a portion of the PhIP bound to albumin in vivo probably occurs as an acid-labile sulfinamide adduct formed at the Cys34 residue.
27984695	8	3	theme	hydrolysis	1619:1628	arg1	pyridine					1607:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	3	theme	hydrolysis	1619:1628	arg1	product					1630:1636	a hydrolysis product	1617:1636	a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP	1617:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	3	4	theme	metabolites	604:614	arg1	reaction					576:583	the reaction	572:583	the reaction of N-oxidized PhIP metabolites with human albumin in vitro	572:642	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	8	5	theme	PhIP	1684:1687	arg1	adduct					1674:1679	the Cys34 S-N linked sulfenamide adduct	1641:1679	the Cys34 S-N linked sulfenamide adduct of PhIP	1641:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	6	located	detected	1698:1705	arg2	product					1630:1636	a hydrolysis product	1617:1636	a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP	1617:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	6	located	detected	1698:1705	arg1	samples					1750:1756	either acid-treated or protease-treated samples	1710:1756	either acid-treated or protease-treated samples	1710:1756	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	6	located	detected	1698:1705	arg2	pyridine					1607:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	7	7	theme	h	1427:1427	arg1	treatment					1403:1411	acid treatment	1398:1411	acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP	1398:1485	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	4	8	theme	[Dingley	978:985	arg1	dose					953:956	a dietary-relevant dose	934:956	a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol.	934:1025	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	7	9	theme	albumin	1416:1422	arg1	h					1427:1427	albumin 24 h	1416:1427	albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP	1416:1485	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	3	10	with	reaction	576:583	arg1	albumin					627:633	human albumin	621:633	human albumin	621:633	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	1	11	theme	carcinogenic	204:215	arg1	pyridine					183:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine	144:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)	144:197	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	1	11	theme	carcinogenic	204:215	arg1	amine					239:243	a carcinogenic heterocyclic aromatic amine	202:243	a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats	202:295	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	9	12	theme	Cys34	1901:1905	arg1	residue					1907:1913	the Cys34 residue	1897:1913	the Cys34 residue	1897:1913	These findings suggest that a portion of the PhIP bound to albumin in vivo probably occurs as an acid-labile sulfinamide adduct formed at the Cys34 residue.
27984695	3	13	theme	Cys34	668:672	arg1	residue					674:680	the Cys34 residue	664:680	the Cys34 residue	664:680	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	1	14	theme	aromatic	230:237	arg1	pyridine					183:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine	144:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)	144:197	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	1	14	theme	aromatic	230:237	arg1	amine					239:243	a carcinogenic heterocyclic aromatic amine	202:243	a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats	202:295	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	6	15	theme	mass	1342:1345	arg1	spectrometry					1347:1358	Orbitrap mass spectrometry	1333:1358	Orbitrap mass spectrometry	1333:1358	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	2	16	theme	amine	360:364	arg1	group					366:370	the exocyclic amine group	346:370	the exocyclic amine group	346:370	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	7	17	theme	PhIP	1380:1383	arg1	amount					1365:1370	The amount	1361:1370	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP	1361:1485	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	7	17	theme	PhIP	1380:1383	arg1	PhIP					1380:1383	[14C]PhIP	1375:1383	[14C]PhIP	1375:1383	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	6	18	theme	similar	1226:1232	arg1	PhIP					1262:1265	covalently bound PhIP	1245:1265	covalently bound PhIP	1245:1265	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	18	theme	similar	1226:1232	arg1	amounts					1234:1240	similar amounts	1226:1240	similar amounts	1226:1240	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	4	19	theme	ultraperformance	793:808	arg1	method					850:855	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	1	20	theme	2-Amino-1-methyl-6-phenylimidazo[4,5-b	144:181	arg1	PhIP					193:196	PhIP	193:196	PhIP	193:196	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	1	20	theme	2-Amino-1-methyl-6-phenylimidazo[4,5-b	144:181	arg1	pyridine					183:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine	144:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)	144:197	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	1	20	theme	2-Amino-1-methyl-6-phenylimidazo[4,5-b	144:181	arg1	amine					239:243	a carcinogenic heterocyclic aromatic amine	202:243	a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats	202:295	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	2	21	theme	P450-mediated	313:325	arg1	N-hydroxylation					327:341	The cytochrome P450-mediated N-hydroxylation	298:341	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP	298:378	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	6	22	with	treatment	1068:1076	arg1	pH					1190:1191	pH 8.5	1190:1195	pH 8.5	1190:1195	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	22	with	treatment	1068:1076	arg1	buffer					1182:1187	Pronase [50 mM ammonium bicarbonate buffer	1146:1187	Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h	1146:1214	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	4	23	theme	chromatography-mass	817:835	arg1	spectrometry					837:848	liquid chromatography-mass spectrometry	810:848	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	6	24	theme	multistage	1295:1304	arg1	scanning					1306:1313	multistage scanning	1295:1313	multistage scanning	1295:1313	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	3	25	theme	sulfinamide	716:726	arg1	adduct					728:733	an acid-labile linked sulfinamide adduct	694:733	an acid-labile linked sulfinamide adduct	694:733	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	6	26	theme	N	1094:1094	arg1	HCl					1096:1098	0.1 N HCl	1090:1098	0.1 N HCl	1090:1098	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	3	27	theme	acid-labile	697:707	arg1	adduct					728:733	an acid-labile linked sulfinamide adduct	694:733	an acid-labile linked sulfinamide adduct	694:733	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	2	28	theme	cytochrome	302:311	arg1	N-hydroxylation					327:341	The cytochrome P450-mediated N-hydroxylation	298:341	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP	298:378	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	4	29	theme	albumin-PhIP	880:891	arg1	adducts					893:899	acid-labile albumin-PhIP adducts	868:899	acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev	868:1042	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	6	30	theme	acid	1063:1066	arg1	treatment					1068:1076	Mild acid treatment	1058:1076	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h]	1058:1215	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	3	31	theme	Previous	515:522	arg1	studies					524:530	Previous studies	515:530	Previous studies conducted by our laboratory	515:558	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	0	32	theme	Mass	0:3	arg1	Characterization					19:34	Mass Spectrometric Characterization	0:34	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.	0:142	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.
27984695	3	33	link	linked	709:714	arg1	adduct					728:733	an acid-labile linked sulfinamide adduct	694:733	an acid-labile linked sulfinamide adduct	694:733	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	8	34	theme	2-Amino-1-methyl-6-	1557:1575	arg1	pyridine					1607:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	34	theme	2-Amino-1-methyl-6-	1557:1575	arg1	product					1630:1636	a hydrolysis product	1617:1636	a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP	1617:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	4	35	theme	14C-labeled	961:971	arg1	[Dingley					978:985	14C-labeled PhIP [Dingley	961:985	14C-labeled PhIP [Dingley	961:985	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	4	35	theme	14C-labeled	961:971	arg1	H.					991:992	H.	991:992	H.	991:992	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	0	36	theme	Adduct	54:59	arg1	Characterization					19:34	Mass Spectrometric Characterization	0:34	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.	0:142	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.
27984695	6	37	theme	PhIP	1262:1265	arg1	PhIP					1262:1265	covalently bound PhIP	1245:1265	covalently bound PhIP	1245:1265	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	37	theme	PhIP	1262:1265	arg1	amounts					1234:1240	similar amounts	1226:1240	similar amounts	1226:1240	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	38	theme	ammonium	1161:1168	arg1	pH					1190:1191	pH 8.5	1190:1195	pH 8.5	1190:1195	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	38	theme	ammonium	1161:1168	arg1	buffer					1182:1187	Pronase [50 mM ammonium bicarbonate buffer	1146:1187	Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h	1146:1214	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	8	39	theme	5-hydroxy	1577:1585	arg1	pyridine					1607:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	39	theme	5-hydroxy	1577:1585	arg1	product					1630:1636	a hydrolysis product	1617:1636	a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP	1617:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	2	40	theme	2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b	389:433	arg1	pyridine					435:442	2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine	389:442	2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine	389:442	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	2	40	theme	2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b	389:433	arg1	metabolite					462:471	an electrophilic metabolite	445:471	an electrophilic metabolite that forms adducts with DNA and proteins	445:512	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	1	41	theme	high-temperature	263:278	arg1	cooking					280:286	the high-temperature cooking	259:286	the high-temperature cooking of meats	259:295	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	6	42	theme	[50	1154:1156	arg1	mM					1158:1159	mM	1158:1159	mM	1158:1159	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	8	43	theme	phenylimidazo[4,5-b	1587:1605	arg1	pyridine					1607:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	43	theme	phenylimidazo[4,5-b	1587:1605	arg1	product					1630:1636	a hydrolysis product	1617:1636	a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP	1617:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	44	theme	S-N	1651:1653	arg1	adduct					1674:1679	the Cys34 S-N linked sulfenamide adduct	1641:1679	the Cys34 S-N linked sulfenamide adduct of PhIP	1641:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	3	45	theme	PhIP	599:602	arg1	metabolites					604:614	N-oxidized PhIP metabolites	588:614	N-oxidized PhIP metabolites	588:614	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	8	46	theme	sulfenamide	1662:1672	arg1	adduct					1674:1679	the Cys34 S-N linked sulfenamide adduct	1641:1679	the Cys34 S-N linked sulfenamide adduct of PhIP	1641:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	6	47	theme	proteolytic	1119:1129	arg1	digestion					1131:1139	proteolytic digestion	1119:1139	proteolytic digestion	1119:1139	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	9	48	theme	sulfinamide	1868:1878	arg1	adduct					1880:1885	an acid-labile sulfinamide adduct	1853:1885	an acid-labile sulfinamide adduct formed at the Cys34 residue	1853:1913	These findings suggest that a portion of the PhIP bound to albumin in vivo probably occurs as an acid-labile sulfinamide adduct formed at the Cys34 residue.
27984695	2	49	theme	exocyclic	350:358	arg1	group					366:370	the exocyclic amine group	346:370	the exocyclic amine group	346:370	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	4	50	theme	PhIP	973:976	arg1	[Dingley					978:985	14C-labeled PhIP [Dingley	961:985	14C-labeled PhIP [Dingley	961:985	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	4	50	theme	PhIP	973:976	arg1	H.					991:992	H.	991:992	H.	991:992	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	6	51	theme	bound	1256:1260	arg1	PhIP					1262:1265	covalently bound PhIP	1245:1265	covalently bound PhIP	1245:1265	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	2	52	theme	PhIP	375:378	arg1	N-hydroxylation					327:341	The cytochrome P450-mediated N-hydroxylation	298:341	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP	298:378	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	1	53	theme	heterocyclic	217:228	arg1	pyridine					183:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine	144:190	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)	144:197	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	1	53	theme	heterocyclic	217:228	arg1	amine					239:243	a carcinogenic heterocyclic aromatic amine	202:243	a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats	202:295	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
27984695	6	54	theme	Mild	1058:1061	arg1	treatment					1068:1076	Mild acid treatment	1058:1076	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h]	1058:1215	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	2	55	theme	group	366:370	arg1	N-hydroxylation					327:341	The cytochrome P450-mediated N-hydroxylation	298:341	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP	298:378	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	0	56	from	pyridine	112:119	arg1	Humans					136:141	Humans	136:141	Humans	136:141	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.
27984695	7	57	theme	acid	1398:1401	arg1	treatment					1403:1411	acid treatment	1398:1411	acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP	1398:1485	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	6	58	theme	Orbitrap	1333:1340	arg1	spectrometry					1347:1358	Orbitrap mass spectrometry	1333:1358	Orbitrap mass spectrometry	1333:1358	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	8	59	theme	acid-treated	1717:1728	arg1	samples					1750:1756	either acid-treated or protease-treated samples	1710:1756	either acid-treated or protease-treated samples	1710:1756	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	60	theme	protease-treated	1733:1748	arg1	samples					1750:1756	either acid-treated or protease-treated samples	1710:1756	either acid-treated or protease-treated samples	1710:1756	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	4	61	theme	sensitive	783:791	arg1	method					850:855	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	3	62	theme	linked	709:714	arg1	adduct					728:733	an acid-labile linked sulfinamide adduct	694:733	an acid-labile linked sulfinamide adduct	694:733	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	4	63	theme	1999	1003:1006	arg1	Cancer					1009:1014	Cancer	1009:1014	Cancer	1009:1014	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	0	64	from	Albumin	125:131	arg1	Humans					136:141	Humans	136:141	Humans	136:141	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.
27984695	4	65	theme	liquid	810:815	arg1	spectrometry					837:848	liquid chromatography-mass spectrometry	810:848	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	0	66	theme	2-Amino-1-methyl-6-phenylimidazo[4,5-b	73:110	arg1	pyridine					112:119	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine	73:119	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine	73:119	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.
27984695	8	67	link	linked	1655:1660	arg1	adduct					1674:1679	the Cys34 S-N linked sulfenamide adduct	1641:1679	the Cys34 S-N linked sulfenamide adduct of PhIP	1641:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	6	68	theme	albumin	1081:1087	arg1	treatment					1068:1076	Mild acid treatment	1058:1076	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h]	1058:1215	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	69	dep	albumin	1081:1087	arg1	HCl					1096:1098	0.1 N HCl	1090:1098	0.1 N HCl	1090:1098	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	4	70	dep	Biomarkers	1028:1037	arg1	Prev					1039:1042	Prev	1039:1042	Prev	1039:1042	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	4	71	from	adducts	893:899	arg1	volunteers					910:919	human volunteers	904:919	human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol.	904:1025	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	4	71	from	adducts	893:899	arg1	Biomarkers					1028:1037	Biomarkers Prev	1028:1042	Biomarkers Prev	1028:1042	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	7	72	theme	mass	1525:1528	arg1	spectrometry					1530:1541	accelerator mass spectrometry	1513:1541	accelerator mass spectrometry measurements	1513:1554	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	4	73	theme	acid-labile	868:878	arg1	adducts					893:899	acid-labile albumin-PhIP adducts	868:899	acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev	868:1042	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	7	74	theme	spectrometry	1530:1541	arg1	measurements					1543:1554	accelerator mass spectrometry measurements	1513:1554	accelerator mass spectrometry measurements	1513:1554	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	6	75	dep	HCl	1096:1098	arg1	°C					1104:1105	37 °C	1101:1105	37 °C for 1 h	1101:1113	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	76	from	°C	1204:1205	arg1	pH					1190:1191	pH 8.5	1190:1195	pH 8.5	1190:1195	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	76	from	°C	1204:1205	arg1	buffer					1182:1187	Pronase [50 mM ammonium bicarbonate buffer	1146:1187	Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h	1146:1214	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	0	77	theme	Spectrometric	5:17	arg1	Characterization					19:34	Mass Spectrometric Characterization	0:34	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.	0:142	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.
27984695	4	78	theme	spectrometry	837:848	arg1	method					850:855	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	a sensitive ultraperformance liquid chromatography-mass spectrometry method	781:855	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	9	79	theme	PhIP	1804:1807	arg1	portion					1789:1795	a portion	1787:1795	a portion of the PhIP bound to albumin in vivo	1787:1832	These findings suggest that a portion of the PhIP bound to albumin in vivo probably occurs as an acid-labile sulfinamide adduct formed at the Cys34 residue.
27984695	0	80	theme	Acid-Labile	42:52	arg1	Adduct					54:59	an Acid-Labile Adduct	39:59	an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans	39:141	Mass Spectrometric Characterization of an Acid-Labile Adduct Formed with 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and Albumin in Humans.
27984695	7	81	theme	accelerator	1513:1523	arg1	spectrometry					1530:1541	accelerator mass spectrometry	1513:1541	accelerator mass spectrometry measurements	1513:1554	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	4	82	theme	dietary-relevant	936:951	arg1	dose					953:956	a dietary-relevant dose	934:956	a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol.	934:1025	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	6	83	theme	bicarbonate	1170:1180	arg1	pH					1190:1191	pH 8.5	1190:1195	pH 8.5	1190:1195	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	83	theme	bicarbonate	1170:1180	arg1	buffer					1182:1187	Pronase [50 mM ammonium bicarbonate buffer	1146:1187	Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h	1146:1214	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	3	84	theme	N-oxidized	588:597	arg1	metabolites					604:614	N-oxidized PhIP metabolites	588:614	N-oxidized PhIP metabolites	588:614	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	8	85	theme	Cys34	1645:1649	arg1	adduct					1674:1679	the Cys34 S-N linked sulfenamide adduct	1641:1679	the Cys34 S-N linked sulfenamide adduct of PhIP	1641:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	4	86	dep	findings	758:765	arg1	the					739:741	the	739:741	the	739:741	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	4	86	dep	findings	758:765	arg1	basis					743:747	basis	743:747	basis	743:747	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	6	87	theme	mM	1158:1159	arg1	pH					1190:1191	pH 8.5	1190:1195	pH 8.5	1190:1195	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	87	theme	mM	1158:1159	arg1	buffer					1182:1187	Pronase [50 mM ammonium bicarbonate buffer	1146:1187	Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h	1146:1214	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	4	88	theme	human	904:908	arg1	volunteers					910:919	human volunteers	904:919	human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol.	904:1025	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	4	88	theme	human	904:908	arg1	Biomarkers					1028:1037	Biomarkers Prev	1028:1042	Biomarkers Prev	1028:1042	On the basis of these findings, we developed a sensitive ultraperformance liquid chromatography-mass spectrometry method to measure acid-labile albumin-PhIP adducts in human volunteers administered a dietary-relevant dose of 14C-labeled PhIP [Dingley, K. H., et al. (1999) Cancer Epidemiol., Biomarkers Prev.
27984695	2	89	theme	electrophilic	448:460	arg1	pyridine					435:442	2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine	389:442	2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine	389:442	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	2	89	theme	electrophilic	448:460	arg1	metabolite					462:471	an electrophilic metabolite	445:471	an electrophilic metabolite that forms adducts with DNA and proteins	445:512	The cytochrome P450-mediated N-hydroxylation of the exocyclic amine group of PhIP produces 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, an electrophilic metabolite that forms adducts with DNA and proteins.
27984695	8	90	theme	linked	1655:1660	arg1	adduct					1674:1679	the Cys34 S-N linked sulfenamide adduct	1641:1679	the Cys34 S-N linked sulfenamide adduct of PhIP	1641:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	7	91	theme	PhIP	1482:1485	arg1	PhIP					1482:1485	the [14C]PhIP	1473:1485	the [14C]PhIP	1473:1485	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	7	91	theme	PhIP	1482:1485	arg1	%					1468:1468	7.2-21.3%	1460:1468	7.2-21.3% of the [14C]PhIP	1460:1485	The amount of [14C]PhIP recovered by acid treatment of albumin 24 h following dosing accounted for 7.2-21.3% of the [14C]PhIP bound to albumin based on accelerator mass spectrometry measurements.
27984695	6	92	theme	Pronase	1146:1152	arg1	pH					1190:1191	pH 8.5	1190:1195	pH 8.5	1190:1195	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	6	92	theme	Pronase	1146:1152	arg1	buffer					1182:1187	Pronase [50 mM ammonium bicarbonate buffer	1146:1187	Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h	1146:1214	Mild acid treatment of albumin (0.1 N HCl, 37 °C for 1 h) or proteolytic digestion with Pronase [50 mM ammonium bicarbonate buffer (pH 8.5) at 37 °C for 18 h] released similar amounts of covalently bound PhIP, which was characterized by multistage scanning and quantified by Orbitrap mass spectrometry.
27984695	3	93	theme	human	621:625	arg1	albumin					627:633	human albumin	621:633	human albumin	621:633	Previous studies conducted by our laboratory showed that the reaction of N-oxidized PhIP metabolites with human albumin in vitro primarily occurs at the Cys34 residue, to produce an acid-labile linked sulfinamide adduct.
27984695	8	94	theme	adduct	1674:1679	arg1	pyridine					1607:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine	1557:1614	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	8	94	theme	adduct	1674:1679	arg1	product					1630:1636	a hydrolysis product	1617:1636	a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP	1617:1687	2-Amino-1-methyl-6-(5-hydroxy)phenylimidazo[4,5-b]pyridine, a hydrolysis product of the Cys34 S-N linked sulfenamide adduct of PhIP, was not detected in either acid-treated or protease-treated samples.
27984695	1	95	theme	meats	291:295	arg1	cooking					280:286	the high-temperature cooking	259:286	the high-temperature cooking of meats	259:295	2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a carcinogenic heterocyclic aromatic amine formed during the high-temperature cooking of meats.
29107940	4	0	theme	MHC-I	578:582	arg1	allomorphs					584:593	different MHC-I allomorphs	568:593	different MHC-I allomorphs	568:593	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	2	1	theme	class	364:368	arg1	molecules					380:388	major histocompatibility complex class I (MHC-I) molecules	331:388	major histocompatibility complex class I (MHC-I) molecules	331:388	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	4	2	dep	processing	744:753	arg1	referred					779:786	referred	779:786	jointly referred to as TAP	771:796	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	3	3	theme	malignant	539:547	arg1	cells					549:553	infected or malignant cells	527:553	infected or malignant cells	527:553	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	4	4	from	assembly	684:691	arg1	coordination					616:627	the precise coordination	604:627	the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin	604:891	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	5	5	theme	molecular	898:906	arg1	organization					908:919	The molecular organization	894:919	The molecular organization of and mechanistic events that take place in the PLC	894:972	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	5	5	theme	molecular	898:906	arg1	unknown					978:984	unknown	978:984	unknown	978:984	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	9	6	theme	MHC-I	1671:1675	arg1	pocket					1693:1698	the MHC-I peptide-binding pocket	1667:1698	the MHC-I peptide-binding pocket	1667:1698	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	6	7	theme	viral	1151:1155	arg1	inhibitor					1157:1165	an engineered viral inhibitor	1137:1165	an engineered viral inhibitor	1137:1165	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	2	8	theme	molecules	380:388	arg1	loading					308:314	loading	308:314	loading	308:314	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	2	8	theme	molecules	380:388	arg1	editing					320:326	editing	320:326	editing	320:326	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	4	9	theme	single	662:667	arg1	assembly					684:691	a single macromolecular assembly	660:691	a single macromolecular assembly	660:691	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	3	10	theme	infected	527:534	arg1	cells					549:553	infected or malignant cells	527:553	infected or malignant cells	527:553	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	12	11	theme	antigenic	1982:1990	arg1	peptides					1992:1999	the antigenic peptides	1978:1999	the antigenic peptides	1978:1999	Two lateral windows channel the antigenic peptides to MHC-I.
29107940	14	12	theme	transporter	2188:2198	arg1	symbiosis					2168:2176	the molecular symbiosis	2154:2176	the molecular symbiosis of an ABC transporter	2154:2198	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	14	12	theme	transporter	2188:2198	arg1	network					2239:2245	an endoplasmic reticulum chaperone network	2204:2245	an endoplasmic reticulum chaperone network in MHC-I assembly	2204:2263	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	11	13	theme	TAP	1825:1827	arg1	pathway					1814:1820	The translocation pathway	1796:1820	The translocation pathway of TAP	1796:1827	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	4	14	theme	different	638:646	arg1	subunits					648:655	seven different subunits	632:655	seven different subunits	632:655	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	14	theme	different	638:646	arg1	ERp57					819:823	the oxidoreductase ERp57	800:823	the oxidoreductase ERp57	800:823	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	14	theme	different	638:646	arg1	transporter					708:718	the transporter	704:718	the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP)	704:797	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	14	theme	different	638:646	arg1	chaperones					857:866	the chaperones tapasin and calreticulin	853:891	the chaperones tapasin and calreticulin	853:891	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	14	theme	different	638:646	arg1	heterodimer					836:846	the MHC-I heterodimer	826:846	the MHC-I heterodimer	826:846	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	5	15	theme	events	940:945	arg1	organization					908:919	The molecular organization	894:919	The molecular organization of and mechanistic events that take place in the PLC	894:972	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	5	15	theme	events	940:945	arg1	unknown					978:984	unknown	978:984	unknown	978:984	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	12	16	theme	lateral	1954:1960	arg1	windows					1962:1968	Two lateral windows	1950:1968	Two lateral windows	1950:1968	Two lateral windows channel the antigenic peptides to MHC-I.
29107940	6	17	theme	PLC	1213:1215	arg1	structure					1193:1201	the structure	1189:1201	the structure of native PLC by electron cryo-microscopy	1189:1243	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	1	18	theme	hierarchical	200:211	arg1	response					220:227	a hierarchical immune response	198:227	a hierarchical immune response	198:227	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	13	19	dep	recruitment	2103:2113	arg1	the					2099:2101	the	2099:2101	the	2099:2101	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	4	20	dep	chaperones	857:866	arg1	chaperones					857:866	the chaperones tapasin and calreticulin	853:891	the chaperones tapasin and calreticulin	853:891	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	20	dep	chaperones	857:866	arg1	calreticulin					880:891	calreticulin	880:891	calreticulin	880:891	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	20	dep	chaperones	857:866	arg1	tapasin					868:874	tapasin	868:874	tapasin	868:874	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	14	21	from	symbiosis	2168:2176	arg1	assembly					2256:2263	MHC-I assembly	2250:2263	MHC-I assembly	2250:2263	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	8	22	theme	editing	1461:1467	arg1	modules					1469:1475	the editing modules	1457:1475	the editing modules	1457:1475	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
29107940	2	23	theme	peptide	250:256	arg1	translocation					258:270	peptide translocation	250:270	peptide translocation into the endoplasmic reticulum	250:301	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	1	24	theme	membrane	117:124	arg1	complex					74:80	The peptide-loading complex	54:80	The peptide-loading complex (PLC)	54:86	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	24	theme	membrane	117:124	arg1	essential					171:179	essential	171:179	essential	171:179	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	24	theme	membrane	117:124	arg1	complex					126:132	a transient, multisubunit membrane complex	91:132	complex	126:132	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	14	25	from	network	2239:2245	arg1	assembly					2256:2263	MHC-I assembly	2250:2263	MHC-I assembly	2250:2263	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	4	26	from	coordination	616:627	arg1	assembly					684:691	a single macromolecular assembly	660:691	a single macromolecular assembly	660:691	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	27	dep	referred	779:786	arg1	TAP2					765:768	TAP2	765:768	TAP2	765:768	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	4	27	dep	referred	779:786	arg1	TAP1					756:759	TAP1	756:759	TAP1	756:759	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	14	28	theme	reticulum	2219:2227	arg1	network					2239:2245	an endoplasmic reticulum chaperone network	2204:2245	an endoplasmic reticulum chaperone network in MHC-I assembly	2204:2263	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	8	29	theme	proofreading	1493:1504	arg1	function					1506:1513	the proofreading function	1489:1513	the proofreading function at two lateral binding platforms for MHC-I molecules	1489:1566	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
29107940	14	30	theme	response	2324:2331	arg1	onset					2295:2299	the onset	2291:2299	the onset of the adaptive immune response	2291:2331	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	1	31	theme	endoplasmic	141:151	arg1	reticulum					153:161	the endoplasmic reticulum	137:161	the endoplasmic reticulum	137:161	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	14	32	theme	adaptive	2308:2315	arg1	response					2324:2331	the adaptive immune response	2304:2331	the adaptive immune response	2304:2331	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	13	33	theme	assembly	2050:2057	arg1	states					2059:2064	distinct assembly states	2041:2064	distinct assembly states	2041:2064	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	2	34	theme	endoplasmic	281:291	arg1	reticulum					293:301	the endoplasmic reticulum	277:301	the endoplasmic reticulum	277:301	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	1	35	from	complex	126:132	arg1	reticulum					153:161	the endoplasmic reticulum	137:161	the endoplasmic reticulum	137:161	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	36	theme	peptide-loading	58:72	arg1	complex					74:80	The peptide-loading complex	54:80	The peptide-loading complex (PLC)	54:86	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	36	theme	peptide-loading	58:72	arg1	essential					171:179	essential	171:179	essential	171:179	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	36	theme	peptide-loading	58:72	arg1	complex					126:132	a transient, multisubunit membrane complex	91:132	complex	126:132	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	36	theme	peptide-loading	58:72	arg1	PLC					83:85	PLC	83:85	PLC	83:85	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	8	37	theme	lateral	1522:1528	arg1	platforms					1538:1546	two lateral binding platforms	1518:1546	two lateral binding platforms for MHC-I molecules	1518:1566	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
29107940	3	38	theme	stable	428:433	arg1	complexes					449:457	stable peptide-MHC-I complexes	428:457	stable peptide-MHC-I complexes	428:457	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	11	39	theme	membrane	1906:1913	arg1	points					1921:1926	the membrane entry points	1902:1926	the membrane entry points of tapasin and MHC-I	1902:1947	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	4	40	theme	MHC-I	830:834	arg1	heterodimer					836:846	the MHC-I heterodimer	826:846	the MHC-I heterodimer	826:846	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	8	41	theme	MHC-I	1552:1556	arg1	molecules					1558:1566	MHC-I molecules	1552:1566	MHC-I molecules	1552:1566	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
29107940	11	42	theme	MHC-I	1943:1947	arg1	points					1921:1926	the membrane entry points	1902:1926	the membrane entry points of tapasin and MHC-I	1902:1947	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	9	43	theme	calreticulin	1595:1606	arg1	domain					1585:1590	The lectin-like domain	1569:1590	The lectin-like domain of calreticulin	1569:1606	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	9	43	theme	calreticulin	1595:1606	arg1	calreticulin					1595:1606	calreticulin	1595:1606	calreticulin	1595:1606	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	4	44	theme	oxidoreductase	804:817	arg1	ERp57					819:823	the oxidoreductase ERp57	800:823	the oxidoreductase ERp57	800:823	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	11	45	theme	tapasin	1931:1937	arg1	points					1921:1926	the membrane entry points	1902:1926	the membrane entry points of tapasin and MHC-I	1902:1947	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	8	46	from	platforms	1538:1546	arg1	function					1506:1513	the proofreading function	1489:1513	the proofreading function at two lateral binding platforms for MHC-I molecules	1489:1566	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
29107940	0	47	theme	MHC-I	23:27	arg1	complex					45:51	the human MHC-I peptide-loading complex	13:51	the human MHC-I peptide-loading complex	13:51	Structure of the human MHC-I peptide-loading complex.
29107940	5	48	theme	heterogeneous	999:1011	arg1	composition					1013:1023	heterogeneous composition	999:1023	heterogeneous composition	999:1023	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	3	49	theme	final	397:401	arg1	proofreading					403:414	final proofreading	397:414	final proofreading in the PLC	397:425	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	13	50	theme	captured	2029:2036	arg1	Structures					2011:2020	Structures	2011:2020	Structures of PLC captured at distinct assembly states	2011:2064	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	2	51	theme	complex	356:362	arg1	class					364:368	major histocompatibility complex class I	331:370	major histocompatibility complex class I (MHC-I) molecules	331:388	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	2	51	theme	complex	356:362	arg1	MHC-I					373:377	MHC-I	373:377	MHC-I	373:377	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	0	52	theme	complex	45:51	arg1	Structure					0:8	Structure	0:8	Structure of the human MHC-I peptide-loading complex	0:51	Structure of the human MHC-I peptide-loading complex.
29107940	7	53	theme	editing	1281:1287	arg1	modules					1289:1295	Two endoplasmic reticulum-resident editing modules	1246:1295	Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I	1246:1347	Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation.
29107940	8	54	theme	multivalent	1409:1419	arg1	network					1431:1437	A multivalent chaperone network	1407:1437	A multivalent chaperone network within and across the editing modules	1407:1475	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
29107940	13	55	theme	distinct	2041:2048	arg1	states					2059:2064	distinct assembly states	2041:2064	distinct assembly states	2041:2064	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	2	56	theme	major	331:335	arg1	class					364:368	major histocompatibility complex class I	331:370	major histocompatibility complex class I (MHC-I) molecules	331:388	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	2	56	theme	major	331:335	arg1	MHC-I					373:377	MHC-I	373:377	MHC-I	373:377	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	1	57	theme	immune	213:218	arg1	response					220:227	a hierarchical immune response	198:227	a hierarchical immune response	198:227	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	10	58	theme	peptide	1761:1767	arg1	editing					1769:1775	peptide editing	1761:1775	peptide editing	1761:1775	This arrangement allows tapasin to facilitate peptide editing by clamping MHC-I.
29107940	7	59	theme	endoplasmic	1250:1260	arg1	modules					1289:1295	Two endoplasmic reticulum-resident editing modules	1246:1295	Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I	1246:1347	Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation.
29107940	3	60	theme	T-cell	503:508	arg1	response					510:517	a T-cell response	501:517	a T-cell response against infected or malignant cells	501:553	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	9	61	theme	P	1645:1645	arg1	domain					1647:1652	the P domain	1641:1652	the P domain	1641:1652	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	4	62	theme	different	568:576	arg1	allomorphs					584:593	different MHC-I allomorphs	568:593	different MHC-I allomorphs	568:593	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	14	63	theme	chaperone	2229:2237	arg1	network					2239:2245	an endoplasmic reticulum chaperone network	2204:2245	an endoplasmic reticulum chaperone network in MHC-I assembly	2204:2263	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	4	64	theme	allomorphs	584:593	arg1	Sampling					556:563	Sampling	556:563	Sampling of different MHC-I allomorphs	556:593	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	14	65	theme	endoplasmic	2207:2217	arg1	reticulum					2219:2227	endoplasmic reticulum	2207:2227	an endoplasmic reticulum chaperone network in MHC-I assembly	2204:2263	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	11	66	theme	lumenal	1874:1880	arg1	cavity					1882:1887	a large endoplasmic reticulum lumenal cavity	1844:1887	a large endoplasmic reticulum lumenal cavity	1844:1887	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	9	67	theme	peptide-binding	1677:1691	arg1	pocket					1693:1698	the MHC-I peptide-binding pocket	1667:1698	the MHC-I peptide-binding pocket	1667:1698	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	6	68	theme	engineered	1140:1149	arg1	inhibitor					1157:1165	an engineered viral inhibitor	1137:1165	an engineered viral inhibitor	1137:1165	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	6	69	theme	electron	1220:1227	arg1	cryo-microscopy					1229:1243	electron cryo-microscopy	1220:1243	electron cryo-microscopy	1220:1243	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	5	70	dep	composition	1013:1023	arg1	the					995:997	the	995:997	the	995:997	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	4	71	theme	macromolecular	669:682	arg1	assembly					684:691	a single macromolecular assembly	660:691	a single macromolecular assembly	660:691	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	14	72	theme	ABC	2184:2186	arg1	transporter					2188:2198	an ABC transporter	2181:2198	an ABC transporter	2181:2198	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	4	73	from	subunits	648:655	arg1	assembly					684:691	a single macromolecular assembly	660:691	a single macromolecular assembly	660:691	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	7	74	theme	pseudo-symmetric	1377:1392	arg1	orientation					1394:1404	a pseudo-symmetric orientation	1375:1404	a pseudo-symmetric orientation	1375:1404	Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation.
29107940	5	75	theme	complex	1065:1071	arg1	nature					1051:1056	intrinsically dynamic nature	1029:1056	intrinsically dynamic nature	1029:1056	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	5	75	theme	complex	1065:1071	arg1	composition					1013:1023	heterogeneous composition	999:1023	heterogeneous composition	999:1023	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	6	76	theme	native	1206:1211	arg1	PLC					1213:1215	native PLC	1206:1215	native PLC	1206:1215	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	4	77	theme	subunits	648:655	arg1	coordination					616:627	the precise coordination	604:627	the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin	604:891	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	14	78	theme	molecular	2158:2166	arg1	symbiosis					2168:2176	the molecular symbiosis	2154:2176	the molecular symbiosis of an ABC transporter	2154:2198	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	11	79	theme	large	1846:1850	arg1	cavity					1882:1887	a large endoplasmic reticulum lumenal cavity	1844:1887	a large endoplasmic reticulum lumenal cavity	1844:1887	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	1	80	theme	transient	93:101	arg1	complex					74:80	The peptide-loading complex	54:80	The peptide-loading complex (PLC)	54:86	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	80	theme	transient	93:101	arg1	essential					171:179	essential	171:179	essential	171:179	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	80	theme	transient	93:101	arg1	complex					126:132	a transient, multisubunit membrane complex	91:132	complex	126:132	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	5	81	theme	dynamic	1043:1049	arg1	nature					1051:1056	intrinsically dynamic nature	1029:1056	intrinsically dynamic nature	1029:1056	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	1	82	theme	multisubunit	104:115	arg1	complex					74:80	The peptide-loading complex	54:80	The peptide-loading complex (PLC)	54:86	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	82	theme	multisubunit	104:115	arg1	essential					171:179	essential	171:179	essential	171:179	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	1	82	theme	multisubunit	104:115	arg1	complex					126:132	a transient, multisubunit membrane complex	91:132	complex	126:132	The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response.
29107940	4	83	theme	antigen	736:742	arg1	processing					744:753	antigen processing	736:753	antigen processing (TAP1 and TAP2, jointly referred to as TAP)	736:797	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	11	84	theme	endoplasmic	1852:1862	arg1	reticulum					1864:1872	endoplasmic reticulum	1852:1872	a large endoplasmic reticulum lumenal cavity	1844:1887	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	13	85	theme	MHC-I	2130:2134	arg1	release					2119:2125	release	2119:2125	release	2119:2125	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	13	85	theme	MHC-I	2130:2134	arg1	recruitment					2103:2113	recruitment	2103:2113	recruitment	2103:2113	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	13	86	from	states	2059:2064	arg1	Structures					2011:2020	Structures	2011:2020	Structures of PLC captured at distinct assembly states	2011:2064	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	3	87	from	proofreading	403:414	arg1	PLC					423:425	the PLC	419:425	the PLC	419:425	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	5	88	dep	events	940:945	arg1	mechanistic					928:938	mechanistic	928:938	mechanistic	928:938	The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex.
29107940	14	89	theme	immune	2317:2322	arg1	response					2324:2331	the adaptive immune response	2304:2331	the adaptive immune response	2304:2331	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	11	90	theme	translocation	1800:1812	arg1	pathway					1814:1820	The translocation pathway	1796:1820	The translocation pathway of TAP	1796:1827	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	6	91	theme	lymphoma	1116:1123	arg1	cells					1125:1129	Burkitt's lymphoma cells	1106:1129	Burkitt's lymphoma cells using an engineered viral inhibitor as bait	1106:1173	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	8	92	theme	binding	1530:1536	arg1	platforms					1538:1546	two lateral binding platforms	1518:1546	two lateral binding platforms for MHC-I molecules	1518:1566	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
29107940	11	93	theme	reticulum	1864:1872	arg1	cavity					1882:1887	a large endoplasmic reticulum lumenal cavity	1844:1887	a large endoplasmic reticulum lumenal cavity	1844:1887	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	3	94	theme	peptide-MHC-I	435:447	arg1	complexes					449:457	stable peptide-MHC-I complexes	428:457	stable peptide-MHC-I complexes	428:457	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	13	95	theme	mechanistic	2074:2084	arg1	insight					2086:2092	mechanistic insight	2074:2092	mechanistic insight into the recruitment and release of MHC-I	2074:2134	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	9	96	theme	lectin-like	1573:1583	arg1	domain					1585:1590	The lectin-like domain	1569:1590	The lectin-like domain of calreticulin	1569:1606	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	9	96	theme	lectin-like	1573:1583	arg1	calreticulin					1595:1606	calreticulin	1595:1606	calreticulin	1595:1606	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	6	97	from	cells	1125:1129	arg1	PLC					1097:1099	human PLC	1091:1099	human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait	1091:1173	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	11	98	theme	entry	1915:1919	arg1	points					1921:1926	the membrane entry points	1902:1926	the membrane entry points of tapasin and MHC-I	1902:1947	The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I.
29107940	0	99	theme	human	17:21	arg1	complex					45:51	the human MHC-I peptide-loading complex	13:51	the human MHC-I peptide-loading complex	13:51	Structure of the human MHC-I peptide-loading complex.
29107940	0	100	theme	peptide-loading	29:43	arg1	complex					45:51	the human MHC-I peptide-loading complex	13:51	the human MHC-I peptide-loading complex	13:51	Structure of the human MHC-I peptide-loading complex.
29107940	13	101	theme	PLC	2025:2027	arg1	captured					2029:2036	PLC captured	2025:2036	PLC captured	2025:2036	Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I.
29107940	9	102	theme	MHC-I	1619:1623	arg1	glycan					1625:1630	the MHC-I glycan	1615:1630	the MHC-I glycan	1615:1630	The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57.
29107940	7	103	theme	reticulum-resident	1262:1279	arg1	modules					1289:1295	Two endoplasmic reticulum-resident editing modules	1246:1295	Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I	1246:1347	Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation.
29107940	2	104	theme	histocompatibility	337:354	arg1	class					364:368	major histocompatibility complex class I	331:370	major histocompatibility complex class I (MHC-I) molecules	331:388	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	2	104	theme	histocompatibility	337:354	arg1	MHC-I					373:377	MHC-I	373:377	MHC-I	373:377	The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules.
29107940	4	105	theme	precise	608:614	arg1	coordination					616:627	the precise coordination	604:627	the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin	604:891	Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.
29107940	3	106	theme	cell	479:482	arg1	surface					484:490	the cell surface	475:490	the cell surface	475:490	After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells.
29107940	6	107	theme	human	1091:1095	arg1	PLC					1097:1099	human PLC	1091:1099	human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait	1091:1173	Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy.
29107940	14	108	theme	MHC-I	2250:2254	arg1	assembly					2256:2263	MHC-I assembly	2250:2263	MHC-I assembly	2250:2263	Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.
29107940	8	109	theme	chaperone	1421:1429	arg1	network					1431:1437	A multivalent chaperone network	1407:1437	A multivalent chaperone network within and across the editing modules	1407:1475	A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules.
31311268	0	0	theme	State	161:165	arg1	Effects					111:117	Effects	111:117	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.	0:208	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	4	1	from	contexts	907:914	arg1	influence					835:843	the influence	831:843	the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA	831:1040	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	5	2	dep	conformations	1147:1159	arg1	stacked					1134:1140	stacked	1134:1140	stacked	1134:1140	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	5	2	dep	conformations	1147:1159	arg1	B-type					1119:1124	B-type	1119:1124	B-type	1119:1124	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	5	2	dep	conformations	1147:1159	arg1	S					1143:1143	S	1143:1143	S	1143:1143	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	5	2	dep	conformations	1147:1159	arg1	B					1127:1127	B	1127:1127	B	1127:1127	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	4	3	theme	prokaryotic	964:974	arg1	sequence					995:1002	a prokaryotic mutational hotspot sequence	962:1002	a prokaryotic mutational hotspot sequence	962:1002	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	3	theme	prokaryotic	964:974	arg1	G1					917:918	G1	917:918	G1	917:918	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	1	4	from	nephropathy	280:290	arg1	rodents					331:337	rodents	331:337	rodents	331:337	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	1	4	from	nephropathy	280:290	arg1	humans					295:300	humans	295:300	humans	295:300	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	6	5	theme	repair	1416:1421	arg1	outcomes					1439:1446	the lesion repair and replication outcomes	1405:1446	the lesion repair and replication outcomes	1405:1446	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	1	6	theme	ubiquitous	234:243	arg1	toxin					250:254	a ubiquitous food toxin	232:254	a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents	232:337	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	1	6	theme	ubiquitous	234:243	arg1	A					221:221	Ochratoxin A	210:221	Ochratoxin A (OTA)	210:227	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	4	7	theme	adducted	1029:1036	arg1	DNA					1038:1040	the adducted DNA	1025:1040	the adducted DNA	1025:1040	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	3	8	from	C8-site	797:803	arg1	preferences					691:701	the conformational preferences	672:701	the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine	672:814	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	9	theme	duplexes	724:731	arg1	preferences					691:701	the conformational preferences	672:701	the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine	672:814	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	8	10	theme	two-base	1794:1801	arg1	helices					1812:1818	the corresponding two-base deletion helices	1776:1818	the corresponding two-base deletion helices	1776:1818	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	8	11	theme	sequence	1625:1632	arg1	context					1634:1640	sequence context	1625:1640	sequence context	1625:1640	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	8	12	theme	deletion	1746:1753	arg1	duplexes					1755:1762	the one-base deletion duplexes	1733:1762	the one-base deletion duplexes	1733:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	7	13	theme	exposure	1542:1549	arg1	mutagenicity					1522:1533	the experimentally reported tissue-specific mutagenicity	1478:1533	the experimentally reported tissue-specific mutagenicity of OTA exposure	1478:1549	This finding correlates with the experimentally reported tissue-specific mutagenicity of OTA exposure.
31311268	4	14	theme	ionization	870:879	arg1	states					881:886	four possible ionization states	856:886	four possible ionization states	856:886	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	8	15	from	disruption	1692:1701	arg1	duplexes					1755:1762	the one-base deletion duplexes	1733:1762	the one-base deletion duplexes	1733:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	3	16	theme	one-base	706:713	arg1	duplexes					724:731	one-base deletion duplexes	706:731	one-base deletion duplexes containing OT-G, the major OTA adduct (addition product)	706:788	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	4	17	dep	contexts	907:914	arg1	contexts					907:914	three sequence contexts	892:914	three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence)	892:1003	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	17	dep	contexts	907:914	arg1	sequence					995:1002	a prokaryotic mutational hotspot sequence	962:1002	a prokaryotic mutational hotspot sequence	962:1002	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	17	dep	contexts	907:914	arg1	G3					928:929	G3	928:929	G3	928:929	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	17	dep	contexts	907:914	arg1	G2					921:922	G2	921:922	G2	921:922	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	17	dep	contexts	907:914	arg1	G1					917:918	G1	917:918	G1	917:918	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	2	18	theme	OTA	495:497	arg1	exposure					499:506	OTA exposure	495:506	OTA exposure	495:506	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	5	19	from	stable	1104:1109	arg1	conformations					1147:1159	two (B-type (B) and stacked (S)) conformations	1114:1159	two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions	1114:1244	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	3	20	theme	OTA-induced	562:572	arg1	mutations					592:600	OTA-induced one-base deletion mutations	562:600	OTA-induced one-base deletion mutations	562:600	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	8	21	theme	stable	1648:1653	arg1	interactions					1667:1678	more stable lesion-site interactions	1643:1678	more stable lesion-site interactions	1643:1678	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	7	22	theme	tissue-specific	1506:1520	arg1	mutagenicity					1522:1533	the experimentally reported tissue-specific mutagenicity	1478:1533	the experimentally reported tissue-specific mutagenicity of OTA exposure	1478:1549	This finding correlates with the experimentally reported tissue-specific mutagenicity of OTA exposure.
31311268	4	23	theme	OT-G	848:851	arg1	influence					835:843	the influence	831:843	the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA	831:1040	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	0	24	theme	Context	131:137	arg1	Effects					111:117	Effects	111:117	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.	0:208	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	3	25	theme	guanine	808:814	arg1	guanine					808:814	guanine	808:814	guanine	808:814	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	25	theme	guanine	808:814	arg1	C8-site					797:803	the C8-site	793:803	the C8-site of guanine	793:814	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	0	26	theme	Adduct	143:148	arg1	State					161:165	Adduct Ionization State	143:165	Adduct Ionization State	143:165	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	4	27	from	OT-G	848:851	arg1	contexts					907:914	three sequence contexts	892:914	three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence)	892:1003	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	27	from	OT-G	848:851	arg1	G2					921:922	G2	921:922	G2	921:922	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	27	from	OT-G	848:851	arg1	G3					928:929	G3	928:929	G3	928:929	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	27	from	OT-G	848:851	arg1	states					881:886	four possible ionization states	856:886	four possible ionization states	856:886	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	27	from	OT-G	848:851	arg1	G1					917:918	G1	917:918	G1	917:918	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	3	28	theme	OTA	760:762	arg1	OT-G					744:747	OT-G	744:747	OT-G	744:747	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	28	theme	OTA	760:762	arg1	adduct					764:769	the major OTA adduct	750:769	the major OTA adduct (addition product)	750:788	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	28	theme	OTA	760:762	arg1	product					781:787	addition product	772:787	addition product	772:787	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	8	29	theme	one-base	1869:1876	arg1	deletions					1878:1886	one-base deletions	1869:1886	one-base deletions	1869:1886	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	4	30	from	influence	835:843	arg1	states					881:886	four possible ionization states	856:886	four possible ionization states	856:886	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	30	from	influence	835:843	arg1	G1					917:918	G1	917:918	G1	917:918	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	30	from	influence	835:843	arg1	G2					921:922	G2	921:922	G2	921:922	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	30	from	influence	835:843	arg1	structure					1012:1020	the structure	1008:1020	the structure of the adducted DNA	1008:1040	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	30	from	influence	835:843	arg1	contexts					907:914	three sequence contexts	892:914	three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence)	892:1003	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	30	from	influence	835:843	arg1	G3					928:929	G3	928:929	G3	928:929	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	3	31	theme	deletion	583:590	arg1	mutations					592:600	OTA-induced one-base deletion mutations	562:600	OTA-induced one-base deletion mutations	562:600	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	6	32	theme	replication	1427:1437	arg1	outcomes					1439:1446	the lesion repair and replication outcomes	1405:1446	the lesion repair and replication outcomes	1405:1446	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	8	33	theme	OTA	1857:1859	arg1	abundance					1844:1852	the greater abundance	1832:1852	the greater abundance of OTA	1832:1859	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	0	34	theme	DNA	76:78	arg1	Adduct					80:85	the Major DNA Adduct	66:85	the Major DNA Adduct Formed by Ochratoxin A	66:108	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	0	35	theme	Lesion	170:175	arg1	Structure					182:190	Lesion Site Structure	170:190	Lesion Site Structure	170:190	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	4	36	theme	sequence	898:905	arg1	contexts					907:914	three sequence contexts	892:914	three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence)	892:1003	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	36	theme	sequence	898:905	arg1	G3					928:929	G3	928:929	G3	928:929	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	36	theme	sequence	898:905	arg1	G2					921:922	G2	921:922	G2	921:922	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	36	theme	sequence	898:905	arg1	G1					917:918	G1	917:918	G1	917:918	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	9	37	theme	structural	1925:1934	arg1	insights					1936:1943	valuable structural insights	1916:1943	valuable structural insights that help explain the experimentally observed mutagenicity associated with OTA	1916:2022	Overall, our work provides valuable structural insights that help explain the experimentally observed mutagenicity associated with OTA.
31311268	8	38	theme	base	1719:1722	arg1	pairs					1724:1728	the flanking base pairs	1706:1728	the flanking base pairs in the one-base deletion duplexes	1706:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	2	39	theme	mutations	469:477	arg1	percentage					439:448	the largest percentage	427:448	the largest percentage (73%) of the total mutations that occur upon OTA exposure	427:506	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	2	39	theme	mutations	469:477	arg1	%					453:453	73%	451:453	73%	451:453	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	8	40	theme	ionization	1604:1613	arg1	state					1615:1619	ionization state	1604:1619	ionization state	1604:1619	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	0	41	theme	Ochratoxin	97:106	arg1	A					108:108	Ochratoxin A	97:108	Ochratoxin A	97:108	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	0	42	theme	Deletion	37:44	arg1	Duplexes					46:53	One-Base Deletion Duplexes	28:53	One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A	28:108	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	0	43	theme	Molecular	0:8	arg1	Dynamics					10:17	Molecular Dynamics	0:17	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.	0:208	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	1	44	theme	food	245:248	arg1	toxin					250:254	a ubiquitous food toxin	232:254	a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents	232:337	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	1	44	theme	food	245:248	arg1	A					221:221	Ochratoxin A	210:221	Ochratoxin A (OTA)	210:227	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	8	45	theme	one-base	1737:1744	arg1	duplexes					1755:1762	the one-base deletion duplexes	1733:1762	the one-base deletion duplexes	1733:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	3	46	contain	containing	733:742	arg1	duplexes					724:731	one-base deletion duplexes	706:731	one-base deletion duplexes containing OT-G, the major OTA adduct (addition product)	706:788	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	46	contain	containing	733:742	arg2	OT-G					744:747	OT-G	744:747	OT-G	744:747	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	46	contain	containing	733:742	arg2	adduct					764:769	the major OTA adduct	750:769	the major OTA adduct (addition product)	750:788	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	6	47	theme	sequence	1288:1295	arg1	context					1297:1303	sequence context	1288:1303	sequence context	1288:1303	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	5	48	theme	damaged	1084:1090	arg1	stable					1104:1109	stable	1104:1109	stable	1104:1109	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	5	48	theme	damaged	1084:1090	arg1	helices					1092:1098	the damaged helices	1080:1098	the damaged helices	1080:1098	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	5	49	link	N-linked	1218:1225	arg1	lesions					1238:1244	common N-linked C8-guanine lesions	1211:1244	common N-linked C8-guanine lesions	1211:1244	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	0	50	theme	One-Base	28:35	arg1	Duplexes					46:53	One-Base Deletion Duplexes	28:53	One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A	28:108	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	1	51	theme	chronic	272:278	arg1	nephropathy					280:290	chronic nephropathy	272:290	chronic nephropathy in humans	272:300	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	3	52	theme	present	607:613	arg1	work					615:618	the present work	603:618	the present work	603:618	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	6	53	theme	adduct	1260:1265	arg1	state					1278:1282	the adduct ionization state	1256:1282	the adduct ionization state	1256:1282	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	3	54	theme	MD	645:646	arg1	simulations					649:659	molecular dynamics (MD) simulations	625:659	molecular dynamics (MD) simulations	625:659	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	6	55	theme	B/S	1353:1355	arg1	heterogeneity					1372:1384	the B/S conformational heterogeneity	1349:1384	the B/S conformational heterogeneity	1349:1384	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	1	56	theme	Ochratoxin	210:219	arg1	OTA					224:226	OTA	224:226	OTA	224:226	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	1	56	theme	Ochratoxin	210:219	arg1	A					221:221	Ochratoxin A	210:221	Ochratoxin A (OTA)	210:227	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	1	56	theme	Ochratoxin	210:219	arg1	toxin					250:254	a ubiquitous food toxin	232:254	a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents	232:337	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	0	57	dep	Study	19:23	arg1	Effects					111:117	Effects	111:117	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.	0:208	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	3	58	theme	dynamics	635:642	arg1	simulations					649:659	molecular dynamics (MD) simulations	625:659	molecular dynamics (MD) simulations	625:659	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	5	59	theme	N-linked	1218:1225	arg1	lesions					1238:1244	common N-linked C8-guanine lesions	1211:1244	common N-linked C8-guanine lesions	1211:1244	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	2	60	theme	mutational	344:353	arg1	spectra					355:361	The mutational spectra	340:361	The mutational spectra of cells exposed to OTA	340:385	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	6	61	theme	helical	1326:1332	arg1	distortion					1334:1343	helical distortion	1326:1343	helical distortion	1326:1343	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	4	62	theme	mutational	976:985	arg1	sequence					995:1002	a prokaryotic mutational hotspot sequence	962:1002	a prokaryotic mutational hotspot sequence	962:1002	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	62	theme	mutational	976:985	arg1	G1					917:918	G1	917:918	G1	917:918	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	0	63	theme	Site	177:180	arg1	Structure					182:190	Lesion Site Structure	170:190	Lesion Site Structure	170:190	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	8	64	theme	adduct	1583:1588	arg1	conformation					1590:1601	the adduct conformation	1579:1601	the adduct conformation	1579:1601	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	4	65	theme	DNA	1038:1040	arg1	structure					1012:1020	the structure	1008:1020	the structure of the adducted DNA	1008:1040	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	8	66	theme	corresponding	1780:1792	arg1	helices					1812:1818	the corresponding two-base deletion helices	1776:1818	the corresponding two-base deletion helices	1776:1818	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	6	67	theme	lesion	1409:1414	arg1	repair					1416:1421	lesion repair	1409:1421	lesion repair	1409:1421	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	0	68	theme	Duplexes	46:53	arg1	Study					19:23	Molecular Dynamics Study	0:23	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.	0:208	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	3	69	theme	conformational	676:689	arg1	preferences					691:701	the conformational preferences	672:701	the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine	672:814	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	8	70	theme	deletion	1803:1810	arg1	helices					1812:1818	the corresponding two-base deletion helices	1776:1818	the corresponding two-base deletion helices	1776:1818	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	7	71	theme	OTA	1538:1540	arg1	exposure					1542:1549	OTA exposure	1538:1549	OTA exposure	1538:1549	This finding correlates with the experimentally reported tissue-specific mutagenicity of OTA exposure.
31311268	5	72	from	conformations	1147:1159	arg1	stable					1104:1109	stable	1104:1109	stable	1104:1109	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	5	72	from	conformations	1147:1159	arg1	helices					1092:1098	the damaged helices	1080:1098	the damaged helices	1080:1098	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	4	73	theme	possible	861:868	arg1	states					881:886	four possible ionization states	856:886	four possible ionization states	856:886	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	3	74	theme	deletion	715:722	arg1	duplexes					724:731	one-base deletion duplexes	706:731	one-base deletion duplexes containing OT-G, the major OTA adduct (addition product)	706:788	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	0	75	theme	Sequence	122:129	arg1	Context					131:137	Sequence Context	122:137	Sequence Context	122:137	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	4	76	from	states	881:886	arg1	influence					835:843	the influence	831:843	the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA	831:1040	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	6	77	theme	heterogeneity	1372:1384	arg1	degree					1316:1321	the degree	1312:1321	the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes	1312:1446	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	7	78	theme	reported	1497:1504	arg1	mutagenicity					1522:1533	the experimentally reported tissue-specific mutagenicity	1478:1533	the experimentally reported tissue-specific mutagenicity of OTA exposure	1478:1549	This finding correlates with the experimentally reported tissue-specific mutagenicity of OTA exposure.
31311268	3	79	theme	major	754:758	arg1	OT-G					744:747	OT-G	744:747	OT-G	744:747	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	79	theme	major	754:758	arg1	adduct					764:769	the major OTA adduct	750:769	the major OTA adduct (addition product)	750:788	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	79	theme	major	754:758	arg1	product					781:787	addition product	772:787	addition product	772:787	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	0	80	theme	Ionization	150:159	arg1	State					161:165	Adduct Ionization State	143:165	Adduct Ionization State	143:165	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	3	81	theme	mutations	592:600	arg1	prevalence					548:557	the prevalence	544:557	the prevalence of OTA-induced one-base deletion mutations	544:600	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	8	82	theme	lesion-site	1655:1665	arg1	interactions					1667:1678	more stable lesion-site interactions	1643:1678	more stable lesion-site interactions	1643:1678	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	8	83	theme	disruption	1692:1701	arg1	lack					1684:1687	lack	1684:1687	lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA	1684:1859	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	8	83	theme	disruption	1692:1701	arg1	interactions					1667:1678	more stable lesion-site interactions	1643:1678	more stable lesion-site interactions	1643:1678	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	3	84	theme	addition	772:779	arg1	adduct					764:769	the major OTA adduct	750:769	the major OTA adduct (addition product)	750:788	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	3	84	theme	addition	772:779	arg1	product					781:787	addition product	772:787	addition product	772:787	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	0	85	theme	Major	70:74	arg1	Adduct					80:85	the Major DNA Adduct	66:85	the Major DNA Adduct Formed by Ochratoxin A	66:108	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	3	86	theme	one-base	574:581	arg1	mutations					592:600	OTA-induced one-base deletion mutations	562:600	OTA-induced one-base deletion mutations	562:600	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	1	87	theme	renal	306:310	arg1	carcinogenicity					312:326	renal carcinogenicity	306:326	renal carcinogenicity in rodents	306:337	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	9	88	theme	valuable	1916:1923	arg1	insights					1936:1943	valuable structural insights	1916:1943	valuable structural insights that help explain the experimentally observed mutagenicity associated with OTA	1916:2022	Overall, our work provides valuable structural insights that help explain the experimentally observed mutagenicity associated with OTA.
31311268	8	89	from	pairs	1724:1728	arg1	duplexes					1755:1762	the one-base deletion duplexes	1733:1762	the one-base deletion duplexes	1733:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	8	90	theme	flanking	1710:1717	arg1	pairs					1724:1728	the flanking base pairs	1706:1728	the flanking base pairs in the one-base deletion duplexes	1706:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	2	91	theme	total	463:467	arg1	mutations					469:477	the total mutations	459:477	the total mutations that occur upon OTA exposure	459:506	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	2	92	theme	cells	366:370	arg1	spectra					355:361	The mutational spectra	340:361	The mutational spectra of cells exposed to OTA	340:385	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	0	93	theme	Dynamics	10:17	arg1	Study					19:23	Molecular Dynamics Study	0:23	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.	0:208	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	8	94	theme	pairs	1724:1728	arg1	disruption					1692:1701	disruption	1692:1701	disruption of the flanking base pairs in the one-base deletion duplexes	1692:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	8	95	theme	greater	1836:1842	arg1	abundance					1844:1852	the greater abundance	1832:1852	the greater abundance of OTA	1832:1859	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	2	96	theme	one-base	399:406	arg1	deletions					408:416	one-base deletions	399:416	one-base deletions	399:416	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	8	97	from	duplexes	1755:1762	arg1	disruption					1692:1701	disruption	1692:1701	disruption of the flanking base pairs in the one-base deletion duplexes	1692:1762	Furthermore, regardless of the adduct conformation, ionization state, or sequence context, more stable lesion-site interactions and lack of disruption of the flanking base pairs in the one-base deletion duplexes compared to the corresponding two-base deletion helices rationalize the greater abundance of OTA induced one-base deletions.
31311268	9	98	theme	observed	1982:1989	arg1	mutagenicity					1991:2002	the experimentally observed mutagenicity	1963:2002	the experimentally observed mutagenicity associated with OTA	1963:2022	Overall, our work provides valuable structural insights that help explain the experimentally observed mutagenicity associated with OTA.
31311268	1	99	from	carcinogenicity	312:326	arg1	rodents					331:337	rodents	331:337	rodents	331:337	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	1	99	from	carcinogenicity	312:326	arg1	humans					295:300	humans	295:300	humans	295:300	Ochratoxin A (OTA) is a ubiquitous food toxin associated with chronic nephropathy in humans and renal carcinogenicity in rodents.
31311268	6	100	theme	ionization	1267:1276	arg1	state					1278:1282	the adduct ionization state	1256:1282	the adduct ionization state	1256:1282	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	2	101	theme	largest	431:437	arg1	percentage					439:448	the largest percentage	427:448	the largest percentage (73%) of the total mutations that occur upon OTA exposure	427:506	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	2	101	theme	largest	431:437	arg1	%					453:453	73%	451:453	73%	451:453	The mutational spectra of cells exposed to OTA reveal that one-base deletions comprise the largest percentage (73%) of the total mutations that occur upon OTA exposure.
31311268	6	102	theme	conformational	1357:1370	arg1	heterogeneity					1372:1384	the B/S conformational heterogeneity	1349:1384	the B/S conformational heterogeneity	1349:1384	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	4	103	from	G3	928:929	arg1	5'-G1G2CG3CC-3					944:957	5'-G1G2CG3CC-3	944:957	5'-G1G2CG3CC-3	944:957	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	103	from	G3	928:929	arg1	NarI					938:941	NarI	938:941	NarI	938:941	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	104	theme	hotspot	987:993	arg1	sequence					995:1002	a prokaryotic mutational hotspot sequence	962:1002	a prokaryotic mutational hotspot sequence	962:1002	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	104	theme	hotspot	987:993	arg1	G1					917:918	G1	917:918	G1	917:918	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	3	105	theme	molecular	625:633	arg1	simulations					649:659	molecular dynamics (MD) simulations	625:659	molecular dynamics (MD) simulations	625:659	To contribute toward understanding the prevalence of OTA-induced one-base deletion mutations, the present work uses molecular dynamics (MD) simulations to analyze the conformational preferences of one-base deletion duplexes containing OT-G, the major OTA adduct (addition product) at the C8-site of guanine.
31311268	5	106	theme	common	1211:1216	arg1	lesions					1238:1244	common N-linked C8-guanine lesions	1211:1244	common N-linked C8-guanine lesions	1211:1244	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	4	107	from	G2	921:922	arg1	5'-G1G2CG3CC-3					944:957	5'-G1G2CG3CC-3	944:957	5'-G1G2CG3CC-3	944:957	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	107	from	G2	921:922	arg1	NarI					938:941	NarI	938:941	NarI	938:941	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	0	108	from	Effects	111:117	arg1	Mutagenicity					196:207	Mutagenicity	196:207	Mutagenicity	196:207	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	0	108	from	Effects	111:117	arg1	Structure					182:190	Lesion Site Structure	170:190	Lesion Site Structure	170:190	Molecular Dynamics Study of One-Base Deletion Duplexes Containing the Major DNA Adduct Formed by Ochratoxin A: Effects of Sequence Context and Adduct Ionization State on Lesion Site Structure and Mutagenicity.
31311268	5	109	theme	C8-guanine	1227:1236	arg1	lesions					1238:1244	common N-linked C8-guanine lesions	1211:1244	common N-linked C8-guanine lesions	1211:1244	Our data reveal that the damaged helices are stable in two (B-type (B) and stacked (S)) conformations that are structurally similar to those adopted by common N-linked C8-guanine lesions.
31311268	6	110	theme	distortion	1334:1343	arg1	degree					1316:1321	the degree	1312:1321	the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes	1312:1446	However, the adduct ionization state and sequence context affect the degree of helical distortion and the B/S conformational heterogeneity, which will impact the lesion repair and replication outcomes.
31311268	4	111	from	G1	917:918	arg1	5'-G1G2CG3CC-3					944:957	5'-G1G2CG3CC-3	944:957	5'-G1G2CG3CC-3	944:957	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31311268	4	111	from	G1	917:918	arg1	NarI					938:941	NarI	938:941	NarI	938:941	Specifically, the influence of OT-G in four possible ionization states and three sequence contexts (G1, G2 and G3 in the NarI (5'-G1G2CG3CC-3'), a prokaryotic mutational hotspot sequence) on the structure of the adducted DNA is investigated.
31059811	12	0	theme	SjLRRs	1957:1962	arg1	redistribution					1939:1952	dramatic redistribution	1930:1952	dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation	1930:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	7	1	theme	same	1197:1200	arg1	clade					1202:1206	the same clade	1193:1206	the same clade	1193:1206	Multiple sequence alignment and phylogenetic analysis revealed that SjTLR shared the highest similarity to that of Euprymna scolopes and they fell into the same clade.
31059811	14	2	theme	related	2145:2151	arg1	genes					2153:2157	The nuclear related genes	2133:2157	The nuclear related genes	2133:2157	The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released.
31059811	14	3	theme	IL-6	2312:2315	arg1	cytokines					2317:2325	IL-6 cytokines	2312:2325	IL-6 cytokines	2312:2325	The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released.
31059811	0	4	from	homologue	60:68	arg1	japonica					82:89	Sepiella japonica	73:89	Sepiella japonica	73:89	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	2	5	from	Sepiella	292:299	arg1	TLR					283:285	the first TLR	273:285	the first TLR from Sepiella japonica (named as SjTLR)	273:325	In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no.
31059811	4	6	theme	theoretical	535:545	arg1	weight					557:562	Its theoretical molecular weight	531:562	Its theoretical molecular weight	531:562	Its theoretical molecular weight was 137.87 KDa and the predicted isoelectric point was 3.69.
31059811	7	7	theme	phylogenetic	1073:1084	arg1	analysis					1086:1093	phylogenetic analysis	1073:1093	phylogenetic analysis	1073:1093	Multiple sequence alignment and phylogenetic analysis revealed that SjTLR shared the highest similarity to that of Euprymna scolopes and they fell into the same clade.
31059811	3	8	theme	putative	493:500	arg1	protein					502:508	a putative protein	491:508	a putative protein of 1193 amino acids	491:528	AQY56780.1) including an open reading frame of 3582bp, encoding a putative protein of 1193 amino acids.
31059811	0	9	theme	aquatic	135:141	arg1	bacteria					154:161	aquatic pathogenic bacteria	135:161	aquatic pathogenic bacteria	135:161	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	8	10	theme	Real-time	1209:1217	arg1	PCR					1219:1221	Real-time PCR	1209:1221	Real-time PCR	1209:1221	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	7	11	theme	Multiple	1041:1048	arg1	alignment					1059:1067	Multiple sequence alignment	1041:1067	Multiple sequence alignment	1041:1067	Multiple sequence alignment and phylogenetic analysis revealed that SjTLR shared the highest similarity to that of Euprymna scolopes and they fell into the same clade.
31059811	14	12	theme	signal	2275:2280	arg1	pathway					2295:2301	the intracellular signal transduction pathway	2257:2301	the intracellular signal transduction pathway	2257:2301	The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released.
31059811	10	13	theme	Ni-NAT	1677:1682	arg1	resin					1694:1698	Ni-NAT Superflow resin	1677:1698	Ni-NAT Superflow resin conforming to the expected molecular weight	1677:1742	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	5	14	theme	transmembrane	814:826	arg1	domain					828:833	transmembrane domain	814:833	transmembrane domain	814:833	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	6	15	theme	N-linked	902:909	arg1	sites					925:929	12 potential N-linked glycosylation sites	889:929	12 potential N-linked glycosylation sites	889:929	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	16	16	theme	immune	2560:2565	arg1	pathways					2577:2584	the innate immune signaling pathways	2549:2584	the innate immune signaling pathways of S.japonica	2549:2598	These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.
31059811	4	17	theme	isoelectric	597:607	arg1	3.69					619:622	3.69	619:622	3.69	619:622	Its theoretical molecular weight was 137.87 KDa and the predicted isoelectric point was 3.69.
31059811	4	17	theme	isoelectric	597:607	arg1	point					609:613	the predicted isoelectric point	583:613	the predicted isoelectric point	583:613	Its theoretical molecular weight was 137.87 KDa and the predicted isoelectric point was 3.69.
31059811	1	18	from	pathogens	237:245	arg1	mollusk					250:256	mollusk	250:256	mollusk	250:256	Toll-like receptors (TLRs) play an important role in defense response to pathogens in mollusk.
31059811	13	19	theme	signaling	2067:2075	arg1	pathway					2077:2083	Toll/NF-κB signaling pathway	2056:2083	Toll/NF-κB signaling pathway	2056:2083	After SjTLR transfection Toll/NF-κB signaling pathway was active in HEK293 treated with LPS and TNFɑ.
31059811	1	20	theme	important	199:207	arg1	role					209:212	an important role	196:212	an important role	196:212	Toll-like receptors (TLRs) play an important role in defense response to pathogens in mollusk.
31059811	8	21	theme	different	1378:1386	arg1	levels					1399:1404	different expression levels	1378:1404	different expression levels	1378:1404	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	12	22	theme	perinuclear	1995:2005	arg1	accumulation					2007:2018	distinct perinuclear accumulation	1986:2018	distinct perinuclear accumulation	1986:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	10	23	theme	domain	1524:1529	arg1	sequences					1538:1546	The functional domain region sequences	1509:1546	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB)	1509:1616	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	5	24	theme	derived	629:635	arg1	sequence					649:656	The derived amino acids sequence	625:656	The derived amino acids sequence	625:656	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	6	25	link	N-linked	902:909	arg1	sites					925:929	12 potential N-linked glycosylation sites	889:929	12 potential N-linked glycosylation sites	889:929	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	9	26	theme	highest	1424:1430	arg1	expression					1432:1441	The highest expression	1420:1441	The highest expression	1420:1441	The highest expression was in the liver, and the lowest was in stomach for both genders.
31059811	16	27	theme	S.japonica	2589:2598	arg1	pathways					2577:2584	the innate immune signaling pathways	2549:2584	the innate immune signaling pathways of S.japonica	2549:2598	These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.
31059811	8	28	theme	tested	1268:1273	arg1	gill					1294:1297	gill	1294:1297	gill	1294:1297	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	muscle					1314:1319	muscle	1314:1319	muscle	1314:1319	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	opticus					1346:1352	lobus opticus	1340:1352	lobus opticus	1340:1352	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	intestine					1322:1330	intestine	1322:1330	intestine	1322:1330	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	stomach					1358:1364	stomach	1358:1364	stomach	1358:1364	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	liver					1300:1304	liver	1300:1304	liver	1300:1304	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	brain					1307:1311	brain	1307:1311	brain	1307:1311	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	heart					1333:1337	heart	1333:1337	heart	1333:1337	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	8	28	theme	tested	1268:1273	arg1	tissues					1275:1281	all tested tissues	1264:1281	all tested tissues	1264:1281	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	5	29	theme	acids	643:647	arg1	sequence					649:656	The derived amino acids sequence	625:656	The derived amino acids sequence	625:656	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	5	30	theme	acids	714:718	arg1	peptide					727:733	26 amino acids signal peptide	705:733	26 amino acids signal peptide	705:733	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	10	31	theme	expected	1718:1725	arg1	weight					1737:1742	the expected molecular weight	1714:1742	the expected molecular weight	1714:1742	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	6	32	from	ectodomain	951:960	arg1	present					936:942	present	936:942	present	936:942	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	0	33	theme	bacteria	154:161	arg1	stress					125:130	the stress	121:130	the stress of aquatic pathogenic bacteria	121:161	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	14	34	theme	corresponding	2214:2226	arg1	mRNA					2228:2231	the corresponding mRNA	2210:2231	the corresponding mRNA	2210:2231	The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released.
31059811	0	35	theme	Sepiella	73:80	arg1	japonica					82:89	Sepiella japonica	73:89	Sepiella japonica	73:89	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	15	36	theme	time-dependent	2475:2488	arg1	manner					2490:2495	time-dependent manner	2475:2495	time-dependent manner	2475:2495	After infection by Vibrio parahemolyticus and Aeromonas hydrophila the expression of SjTLR were upregulated with time-dependent manner.
31059811	5	37	theme	Toll/IL-1R	851:860	arg1	TIR					870:872	TIR	870:872	TIR	870:872	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	5	37	theme	Toll/IL-1R	851:860	arg1	domain					862:867	cytoplasmic Toll/IL-1R domain	839:867	cytoplasmic Toll/IL-1R domain (TIR)	839:873	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	6	38	located	present	936:942	arg1	addition					879:886	addition	879:886	addition	879:886	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	38	located	present	936:942	arg2	sites					925:929	12 potential N-linked glycosylation sites	889:929	12 potential N-linked glycosylation sites	889:929	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	38	located	present	936:942	arg1	ectodomain					951:960	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	11	39	theme	plasma	1814:1819	arg1	localization					1830:1841	plasma membrane localization	1814:1841	plasma membrane localization	1814:1841	The cellular localization of SjTLR in HEK293 cells was conducted and plasma membrane localization was detected.
31059811	7	40	theme	Euprymna	1156:1163	arg1	scolopes					1165:1172	Euprymna scolopes	1156:1172	Euprymna scolopes	1156:1172	Multiple sequence alignment and phylogenetic analysis revealed that SjTLR shared the highest similarity to that of Euprymna scolopes and they fell into the same clade.
31059811	15	41	theme	SjTLR	2447:2451	arg1	expression					2433:2442	the expression	2429:2442	the expression of SjTLR	2429:2451	After infection by Vibrio parahemolyticus and Aeromonas hydrophila the expression of SjTLR were upregulated with time-dependent manner.
31059811	6	42	theme	ligand	1021:1026	arg1	recognition					1028:1038	ligand recognition	1021:1038	ligand recognition	1021:1038	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	2	43	theme	GenBank	405:411	arg1	no					423:424	3914bp (GenBank accession no	397:424	3914bp (GenBank accession no	397:424	In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no.
31059811	10	44	theme	domain	1562:1567	arg1	protein					1569:1575	LRRs domain protein	1557:1575	LRRs domain protein	1557:1575	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	0	45	theme	Molecular	0:8	arg1	insights					10:17	Molecular insights	0:17	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.	0:162	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	2	46	theme	3914bp	397:402	arg1	no					423:424	3914bp (GenBank accession no	397:424	3914bp (GenBank accession no	397:424	In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no.
31059811	2	47	theme	full-length	367:377	arg1	cDNA					379:382	its full-length cDNA	363:382	its full-length cDNA	363:382	In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no.
31059811	10	48	theme	domain	1585:1590	arg1	TcpB					1612:1615	TcpB	1612:1615	TcpB	1612:1615	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	10	48	theme	domain	1585:1590	arg1	protein					1603:1609	TIR domain containing protein	1581:1609	TIR domain containing protein (TcpB)	1581:1616	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	0	49	theme	novel	24:28	arg1	receptor					51:58	a novel cephalopod toll-like receptor	22:58	a novel cephalopod toll-like receptor homologue	22:68	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	6	50	theme	protein	975:981	arg1	trafficking					983:993	protein trafficking	975:993	protein trafficking	975:993	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	0	51	theme	homologue	60:68	arg1	insights					10:17	Molecular insights	0:17	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.	0:162	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	8	52	theme	lobus	1340:1344	arg1	opticus					1346:1352	lobus opticus	1340:1352	lobus opticus	1340:1352	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	0	53	theme	toll-like	41:49	arg1	receptor					51:58	a novel cephalopod toll-like receptor	22:58	a novel cephalopod toll-like receptor homologue	22:68	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	11	54	theme	SjTLR	1774:1778	arg1	localization					1758:1769	The cellular localization	1745:1769	The cellular localization of SjTLR in HEK293 cells	1745:1794	The cellular localization of SjTLR in HEK293 cells was conducted and plasma membrane localization was detected.
31059811	4	55	theme	molecular	547:555	arg1	weight					557:562	Its theoretical molecular weight	531:562	Its theoretical molecular weight	531:562	Its theoretical molecular weight was 137.87 KDa and the predicted isoelectric point was 3.69.
31059811	1	56	theme	defense	217:223	arg1	response					225:232	defense response	217:232	defense response to pathogens in mollusk	217:256	Toll-like receptors (TLRs) play an important role in defense response to pathogens in mollusk.
31059811	0	57	theme	receptor	51:58	arg1	homologue					60:68	a novel cephalopod toll-like receptor homologue	22:68	a novel cephalopod toll-like receptor homologue	22:68	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	12	58	from	SjLRRs	1957:1962	arg1	cytoplasm					1971:1979	the cytoplasm	1967:1979	the cytoplasm with distinct perinuclear accumulation	1967:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	16	59	theme	host-pathogen	2631:2643	arg1	interactions					2645:2656	host-pathogen interactions	2631:2656	host-pathogen interactions	2631:2656	These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.
31059811	16	60	theme	innate	2553:2558	arg1	pathways					2577:2584	the innate immune signaling pathways	2549:2584	the innate immune signaling pathways of S.japonica	2549:2598	These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.
31059811	3	61	theme	reading	457:463	arg1	frame					465:469	an open reading frame	449:469	an open reading frame	449:469	AQY56780.1) including an open reading frame of 3582bp, encoding a putative protein of 1193 amino acids.
31059811	12	62	from	redistribution	1939:1952	arg1	cytoplasm					1971:1979	the cytoplasm	1967:1979	the cytoplasm with distinct perinuclear accumulation	1967:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	14	63	theme	nuclear	2137:2143	arg1	genes					2153:2157	The nuclear related genes	2133:2157	The nuclear related genes	2133:2157	The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released.
31059811	12	64	with	cytoplasm	1971:1979	arg1	accumulation					2007:2018	distinct perinuclear accumulation	1986:2018	distinct perinuclear accumulation	1986:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	6	65	attach	present	936:942	arg1	addition					879:886	addition	879:886	addition	879:886	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	65	attach	present	936:942	arg2	sites					925:929	12 potential N-linked glycosylation sites	889:929	12 potential N-linked glycosylation sites	889:929	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	65	attach	present	936:942	arg1	ectodomain					951:960	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	7	66	theme	sequence	1050:1057	arg1	alignment					1059:1067	Multiple sequence alignment	1041:1067	Multiple sequence alignment	1041:1067	Multiple sequence alignment and phylogenetic analysis revealed that SjTLR shared the highest similarity to that of Euprymna scolopes and they fell into the same clade.
31059811	1	67	theme	Toll-like	164:172	arg1	TLRs					185:188	TLRs	185:188	TLRs	185:188	Toll-like receptors (TLRs) play an important role in defense response to pathogens in mollusk.
31059811	1	67	theme	Toll-like	164:172	arg1	receptors					174:182	Toll-like receptors	164:182	Toll-like receptors (TLRs)	164:189	Toll-like receptors (TLRs) play an important role in defense response to pathogens in mollusk.
31059811	10	68	theme	functional	1513:1522	arg1	sequences					1538:1546	The functional domain region sequences	1509:1546	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB)	1509:1616	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	6	69	gly	glycosylation	911:923	arg1	addition					879:886	addition	879:886	addition	879:886	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	69	gly	glycosylation	911:923	arg2	sites					925:929	12 potential N-linked glycosylation sites	889:929	12 potential N-linked glycosylation sites	889:929	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	69	gly	glycosylation	911:923	arg2	12					889:890	12	889:890	12	889:890	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	69	gly	glycosylation	911:923	arg1	ectodomain					951:960	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	10	70	theme	Superflow	1684:1692	arg1	resin					1694:1698	Ni-NAT Superflow resin	1677:1698	Ni-NAT Superflow resin conforming to the expected molecular weight	1677:1742	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	6	71	theme	glycosylation	911:923	arg1	sites					925:929	12 potential N-linked glycosylation sites	889:929	12 potential N-linked glycosylation sites	889:929	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	14	72	theme	intracellular	2261:2273	arg1	pathway					2295:2301	the intracellular signal transduction pathway	2257:2301	the intracellular signal transduction pathway	2257:2301	The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released.
31059811	2	73	theme	first	277:281	arg1	TLR					283:285	the first TLR	273:285	the first TLR from Sepiella japonica (named as SjTLR)	273:325	In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no.
31059811	3	74	theme	amino	518:522	arg1	acids					524:528	1193 amino acids	513:528	1193 amino acids	513:528	AQY56780.1) including an open reading frame of 3582bp, encoding a putative protein of 1193 amino acids.
31059811	6	75	theme	potential	892:900	arg1	sites					925:929	12 potential N-linked glycosylation sites	889:929	12 potential N-linked glycosylation sites	889:929	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	0	76	from	japonica	82:89	arg1	insights					10:17	Molecular insights	0:17	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.	0:162	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	13	77	theme	Toll/NF-κB	2056:2065	arg1	pathway					2077:2083	Toll/NF-κB signaling pathway	2056:2083	Toll/NF-κB signaling pathway	2056:2083	After SjTLR transfection Toll/NF-κB signaling pathway was active in HEK293 treated with LPS and TNFɑ.
31059811	12	78	theme	SjLRRs	1857:1862	arg1	internalization					1864:1878	SjLRRs internalization	1857:1878	SjLRRs internalization upon the activation of LPS	1857:1905	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	8	79	theme	expression	1388:1397	arg1	levels					1399:1404	different expression levels	1378:1404	different expression levels	1378:1404	Real-time PCR showed SjTLR expressed constitutively in all tested tissues, including gill, liver, brain, muscle, intestine, heart, lobus opticus and stomach, but showed different expression levels with genders.
31059811	4	80	theme	predicted	587:595	arg1	3.69					619:622	3.69	619:622	3.69	619:622	Its theoretical molecular weight was 137.87 KDa and the predicted isoelectric point was 3.69.
31059811	4	80	theme	predicted	587:595	arg1	point					609:613	the predicted isoelectric point	583:613	the predicted isoelectric point	583:613	Its theoretical molecular weight was 137.87 KDa and the predicted isoelectric point was 3.69.
31059811	10	81	theme	region	1531:1536	arg1	sequences					1538:1546	The functional domain region sequences	1509:1546	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB)	1509:1616	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	14	82	theme	transduction	2282:2293	arg1	pathway					2295:2301	the intracellular signal transduction pathway	2257:2301	the intracellular signal transduction pathway	2257:2301	The nuclear related genes may also be activated by NF-κB in the nucleus, and the corresponding mRNA was transferred through the intracellular signal transduction pathway, so that IL-6 cytokines could be synthesized and released.
31059811	0	83	theme	pathogenic	143:152	arg1	bacteria					154:161	aquatic pathogenic bacteria	135:161	aquatic pathogenic bacteria	135:161	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	3	84	theme	acids	524:528	arg1	protein					502:508	a putative protein	491:508	a putative protein of 1193 amino acids	491:528	AQY56780.1) including an open reading frame of 3582bp, encoding a putative protein of 1193 amino acids.
31059811	12	85	theme	distinct	1986:1993	arg1	accumulation					2007:2018	distinct perinuclear accumulation	1986:2018	distinct perinuclear accumulation	1986:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	5	86	theme	amino	637:641	arg1	sequence					649:656	The derived amino acids sequence	625:656	The derived amino acids sequence	625:656	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	5	87	theme	amino	708:712	arg1	acids					714:718	26 amino acids	705:718	26 amino acids signal peptide	705:733	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	13	88	theme	SjTLR	2037:2041	arg1	transfection					2043:2054	SjTLR transfection	2037:2054	SjTLR transfection	2037:2054	After SjTLR transfection Toll/NF-κB signaling pathway was active in HEK293 treated with LPS and TNFɑ.
31059811	10	89	theme	molecular	1727:1735	arg1	weight					1737:1742	the expected molecular weight	1714:1742	the expected molecular weight	1714:1742	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	12	90	from	cytoplasm	1971:1979	arg1	redistribution					1939:1952	dramatic redistribution	1930:1952	dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation	1930:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	12	91	theme	LPS	1903:1905	arg1	activation					1889:1898	the activation	1885:1898	the activation of LPS	1885:1905	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	5	92	theme	signal	720:725	arg1	peptide					727:733	26 amino acids signal peptide	705:733	26 amino acids signal peptide	705:733	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	16	93	theme	signaling	2567:2575	arg1	pathways					2577:2584	the innate immune signaling pathways	2549:2584	the innate immune signaling pathways of S.japonica	2549:2598	These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.
31059811	5	94	theme	cytoplasmic	839:849	arg1	TIR					870:872	TIR	870:872	TIR	870:872	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	5	94	theme	cytoplasmic	839:849	arg1	domain					862:867	cytoplasmic Toll/IL-1R domain	839:867	cytoplasmic Toll/IL-1R domain (TIR)	839:873	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	5	95	dep	comprised	658:666	arg1	capped					774:779	capped	774:779	capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR)	774:873	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	0	96	from	insights	10:17	arg1	japonica					82:89	Sepiella japonica	73:89	Sepiella japonica	73:89	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	5	97	theme	extracellular	674:686	arg1	domain					688:693	an extracellular domain	671:693	an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR)	671:771	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	16	98	from	studies	2620:2626	arg1	interactions					2645:2656	host-pathogen interactions	2631:2656	host-pathogen interactions	2631:2656	These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.
31059811	11	99	theme	cellular	1749:1756	arg1	localization					1758:1769	The cellular localization	1745:1769	The cellular localization of SjTLR in HEK293 cells	1745:1794	The cellular localization of SjTLR in HEK293 cells was conducted and plasma membrane localization was detected.
31059811	11	100	theme	membrane	1821:1828	arg1	localization					1830:1841	plasma membrane localization	1814:1841	plasma membrane localization	1814:1841	The cellular localization of SjTLR in HEK293 cells was conducted and plasma membrane localization was detected.
31059811	6	101	from	present	936:942	arg1	addition					879:886	addition	879:886	addition	879:886	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	6	101	from	present	936:942	arg1	ectodomain					951:960	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	the ectodomain to influence protein trafficking, surface presentation and ligand recognition	947:1038	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	11	102	from	localization	1758:1769	arg1	HEK293 cells					1783:1794	HEK293 cells	1783:1794	HEK293 cells	1783:1794	The cellular localization of SjTLR in HEK293 cells was conducted and plasma membrane localization was detected.
31059811	2	103	dep	Sepiella	292:299	arg1	japonica					301:308	Sepiella japonica	292:308	Sepiella japonica	292:308	In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no.
31059811	10	104	theme	LRRs	1557:1560	arg1	protein					1569:1575	LRRs domain protein	1557:1575	LRRs domain protein	1557:1575	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	7	105	theme	highest	1126:1132	arg1	similarity					1134:1143	the highest similarity	1122:1143	the highest similarity to that of Euprymna scolopes	1122:1172	Multiple sequence alignment and phylogenetic analysis revealed that SjTLR shared the highest similarity to that of Euprymna scolopes and they fell into the same clade.
31059811	6	106	theme	surface	996:1002	arg1	presentation					1004:1015	surface presentation	996:1015	surface presentation	996:1015	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	13	107	from	HEK293	2099:2104	arg1	active					2089:2094	active	2089:2094	active	2089:2094	After SjTLR transfection Toll/NF-κB signaling pathway was active in HEK293 treated with LPS and TNFɑ.
31059811	10	108	theme	containing	1592:1601	arg1	TcpB					1612:1615	TcpB	1612:1615	TcpB	1612:1615	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	10	108	theme	containing	1592:1601	arg1	protein					1603:1609	TIR domain containing protein	1581:1609	TIR domain containing protein (TcpB)	1581:1616	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	0	109	theme	cephalopod	30:39	arg1	receptor					51:58	a novel cephalopod toll-like receptor	22:58	a novel cephalopod toll-like receptor homologue	22:68	Molecular insights of a novel cephalopod toll-like receptor homologue in Sepiella japonica, revealing its function under the stress of aquatic pathogenic bacteria.
31059811	13	110	from	active	2089:2094	arg1	HEK293					2099:2104	HEK293	2099:2104	HEK293 treated with LPS and TNFɑ	2099:2130	After SjTLR transfection Toll/NF-κB signaling pathway was active in HEK293 treated with LPS and TNFɑ.
31059811	10	111	theme	TIR	1581:1583	arg1	TcpB					1612:1615	TcpB	1612:1615	TcpB	1612:1615	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	10	111	theme	TIR	1581:1583	arg1	protein					1603:1609	TIR domain containing protein	1581:1609	TIR domain containing protein (TcpB)	1581:1616	The functional domain region sequences encoding LRRs domain protein and TIR domain containing protein (TcpB) were expressed in BL21(DE3) respectively and purified with Ni-NAT Superflow resin conforming to the expected molecular weight.
31059811	5	112	theme	leucine-rich	746:757	arg1	LRR					768:770	LRR	768:770	LRR	768:770	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	5	112	theme	leucine-rich	746:757	arg1	repeats					759:765	eleven leucine-rich repeats	739:765	eleven leucine-rich repeats (LRR)	739:771	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	12	113	theme	dramatic	1930:1937	arg1	redistribution					1939:1952	dramatic redistribution	1930:1952	dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation	1930:2018	SjLRRs internalization upon the activation of LPS was also observed, and dramatic redistribution of SjLRRs in the cytoplasm with distinct perinuclear accumulation was found.
31059811	16	114	theme	future	2613:2618	arg1	studies					2620:2626	future studies	2613:2626	future studies on host-pathogen interactions	2613:2656	These findings might be valuable for understanding the innate immune signaling pathways of S.japonica and enabling future studies on host-pathogen interactions.
31059811	2	115	theme	accession	413:421	arg1	no					423:424	3914bp (GenBank accession no	397:424	3914bp (GenBank accession no	397:424	In this study the first TLR from Sepiella japonica (named as SjTLR) was functionally characterized, and its full-length cDNA consisted of 3914bp (GenBank accession no.
31059811	3	116	theme	open	452:455	arg1	frame					465:469	an open reading frame	449:469	an open reading frame	449:469	AQY56780.1) including an open reading frame of 3582bp, encoding a putative protein of 1193 amino acids.
31059811	6	117	from	addition	879:886	arg1	present					936:942	present	936:942	present	936:942	In addition, 12 potential N-linked glycosylation sites were present in the ectodomain to influence protein trafficking, surface presentation and ligand recognition.
31059811	5	118	link	derived	629:635	arg1	sequence					649:656	The derived amino acids sequence	625:656	The derived amino acids sequence	625:656	The derived amino acids sequence comprised of an extracellular domain including 26 amino acids signal peptide and eleven leucine-rich repeats (LRR), capped with LRRCT and LRRNT followed by transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR).
31059811	3	119	theme	3582bp	474:479	arg1	frame					465:469	an open reading frame	449:469	an open reading frame	449:469	AQY56780.1) including an open reading frame of 3582bp, encoding a putative protein of 1193 amino acids.
29688069	0	0	theme	hepatitis	77:85	arg1	treatment					64:72	the treatment	60:72	the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions	60:145	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	1	1	theme	various	348:354	arg1	types					356:360	various types	348:360	various types of hepatitis	348:373	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	5	2	theme	biological	1107:1116	arg1	activities					1118:1127	the biological activities	1103:1127	the biological activities of type-I interferon	1103:1148	These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon.
29688069	1	3	theme	multifaceted	163:174	arg1	effects					215:221	its multifaceted anti-inflammatory and immunomodulatory effects	159:221	its multifaceted anti-inflammatory and immunomodulatory effects	159:221	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	4	4	theme	RAW264.7	917:924	arg1	cells					926:930	RAW264.7 cells	917:930	RAW264.7 cells	917:930	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	1	5	theme	types	356:360	arg1	treatment					335:343	the treatment	331:343	the treatment of various types of hepatitis	331:373	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	2	6	theme	fusion	612:617	arg1	technology					619:628	albumin fusion technology	604:628	albumin fusion technology	604:628	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	1	7	theme	anti-inflammatory	176:192	arg1	effects					215:221	its multifaceted anti-inflammatory and immunomodulatory effects	159:221	its multifaceted anti-inflammatory and immunomodulatory effects	159:221	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	5	8	theme	Man-HSA	1072:1078	arg1	-IFNα2b					1086:1092	Man-HSA(D494N)-IFNα2b	1072:1092	Man-HSA(D494N)-IFNα2b	1072:1092	These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon.
29688069	4	9	theme	Kupffer	951:957	arg1	cells					959:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	5	10	theme	interferon	1139:1148	arg1	activities					1118:1127	the biological activities	1103:1127	the biological activities of type-I interferon	1103:1148	These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon.
29688069	2	11	theme	albumin	604:610	arg1	technology					619:628	albumin fusion technology	604:628	albumin fusion technology	604:628	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	7	12	theme	hepato-protective	1418:1434	arg1	effects					1436:1442	hepato-protective effects	1418:1442	hepato-protective effects	1418:1442	Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects.
29688069	4	13	theme	isolated	942:949	arg1	cells					959:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	1	14	theme	hepatitis	365:373	arg1	types					356:360	various types	348:360	various types of hepatitis	348:373	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	4	15	theme	IL-10	893:897	arg1	cells					959:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	2	16	theme	type-I	440:445	arg1	interferon					447:456	a Kupffer cell targeting type-I interferon	415:456	a Kupffer cell targeting type-I interferon	415:456	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	16	theme	type-I	440:445	arg1	protein					484:490	an albumin-IFNα2b fusion protein	459:490	an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	459:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	7	17	theme	Con-A	1389:1393	arg1	challenge					1395:1403	the Con-A challenge	1385:1403	the Con-A challenge	1385:1403	Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects.
29688069	2	18	theme	oligosaccharide	535:549	arg1	D494N					567:571	D494N	567:571	D494N	567:571	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	18	theme	oligosaccharide	535:549	arg1	chains					551:556	highly mannosylated N-linked oligosaccharide chains	506:556	highly mannosylated N-linked oligosaccharide chains	506:556	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	19	theme	Kupffer	417:423	arg1	interferon					447:456	a Kupffer cell targeting type-I interferon	415:456	a Kupffer cell targeting type-I interferon	415:456	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	19	theme	Kupffer	417:423	arg1	protein					484:490	an albumin-IFNα2b fusion protein	459:490	an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	459:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	6	20	theme	-induced	1235:1242	arg1	mice					1260:1263	Concanavalin A (Con-A)-induced hepatitis model mice	1213:1263	Concanavalin A (Con-A)-induced hepatitis model mice	1213:1263	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	0	21	theme	anti-inflammatory	100:116	arg1	actions					139:145	anti-inflammatory and immunomodulatory actions	100:145	actions	139:145	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	8	22	theme	cell	1554:1557	arg1	interferon					1576:1585	Kupffer cell targeting type-I interferon	1546:1585	Kupffer cell targeting type-I interferon	1546:1585	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	6	23	theme	model	1254:1258	arg1	mice					1260:1263	Concanavalin A (Con-A)-induced hepatitis model mice	1213:1263	Concanavalin A (Con-A)-induced hepatitis model mice	1213:1263	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	7	24	theme	D494N	1358:1362	arg1	post-administration					1327:1345	the post-administration	1323:1345	the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge	1323:1403	Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects.
29688069	1	25	theme	immunomodulatory	198:213	arg1	effects					215:221	its multifaceted anti-inflammatory and immunomodulatory effects	159:221	its multifaceted anti-inflammatory and immunomodulatory effects	159:221	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	4	26	theme	interferon	1026:1035	arg1	receptor					1037:1044	the interferon receptor	1022:1044	the interferon receptor	1022:1044	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	4	27	from	induction	861:869	arg1	levels					883:888	the mRNA levels	874:888	the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	874:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	2	28	theme	site-directed	634:646	arg1	mutagenesis					648:658	site-directed mutagenesis	634:658	site-directed mutagenesis	634:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	8	29	theme	type-I	1569:1574	arg1	interferon					1576:1585	Kupffer cell targeting type-I interferon	1546:1585	Kupffer cell targeting type-I interferon	1546:1585	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	6	30	theme	D494N	1159:1163	arg1	-IFNα2b					1165:1171	Man-HSA(D494N)-IFNα2b	1151:1171	Man-HSA(D494N)-IFNα2b	1151:1171	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	2	31	theme	interferon	447:456	arg1	preparation					400:410	the preparation	396:410	the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	396:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	3	32	theme	Kupffer	786:792	arg1	cells					794:798	Kupffer cells	786:798	Kupffer cells	786:798	The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells.
29688069	4	33	from	IL-1Ra	900:905	arg1	cells					926:930	RAW264.7 cells	917:930	RAW264.7 cells	917:930	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	2	34	gly	mannosylated	513:524	arg1	D494N					567:571	D494N	567:571	D494N	567:571	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	34	gly	mannosylated	513:524	arg1	chains					551:556	highly mannosylated N-linked oligosaccharide chains	506:556	highly mannosylated N-linked oligosaccharide chains	506:556	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	0	35	theme	cell	23:26	arg1	interferon					45:54	Kupffer cell targeting type-I interferon	15:54	Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions	15:145	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	1	36	theme	novel	305:309	arg1	type					311:314	a novel type	303:314	a novel type of therapy for the treatment of various types of hepatitis	303:373	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	6	37	theme	Man-HSA	1151:1157	arg1	-IFNα2b					1165:1171	Man-HSA(D494N)-IFNα2b	1151:1171	Man-HSA(D494N)-IFNα2b	1151:1171	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	1	38	theme	delivering	224:233	arg1	interferon					242:251	delivering type-I interferon	224:251	delivering type-I interferon to Kupffer cells	224:268	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	0	39	theme	Kupffer	15:21	arg1	interferon					45:54	Kupffer cell targeting type-I interferon	15:54	Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions	15:145	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	4	40	from	IL-10	893:897	arg1	cells					926:930	RAW264.7 cells	917:930	RAW264.7 cells	917:930	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	0	41	theme	immunomodulatory	122:137	arg1	actions					139:145	anti-inflammatory and immunomodulatory actions	100:145	actions	139:145	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	4	42	from	mouse	936:940	arg1	cells					926:930	RAW264.7 cells	917:930	RAW264.7 cells	917:930	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	4	43	theme	mRNA	878:881	arg1	levels					883:888	the mRNA levels	874:888	the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	874:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	1	44	theme	type-I	235:240	arg1	interferon					242:251	delivering type-I interferon	224:251	delivering type-I interferon to Kupffer cells	224:268	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	0	45	theme	type-I	38:43	arg1	interferon					45:54	Kupffer cell targeting type-I interferon	15:54	Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions	15:145	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	8	46	theme	interferon	1576:1585	arg1	effectiveness					1517:1529	therapeutic effectiveness	1505:1529	therapeutic effectiveness	1505:1529	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	8	46	theme	interferon	1576:1585	arg1	utility					1535:1541	utility	1535:1541	utility	1535:1541	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	4	47	theme	mouse	936:940	arg1	cells					959:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	7	48	from	2 h	1375:1377	arg1	post-administration					1327:1345	the post-administration	1323:1345	the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge	1323:1403	Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects.
29688069	0	49	theme	targeting	28:36	arg1	interferon					45:54	Kupffer cell targeting type-I interferon	15:54	Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions	15:145	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	1	50	theme	therapy	319:325	arg1	type					311:314	a novel type	303:314	a novel type of therapy for the treatment of various types of hepatitis	303:373	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	2	51	theme	fusion	477:482	arg1	interferon					447:456	a Kupffer cell targeting type-I interferon	415:456	a Kupffer cell targeting type-I interferon	415:456	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	51	theme	fusion	477:482	arg1	protein					484:490	an albumin-IFNα2b fusion protein	459:490	an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	459:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	5	52	theme	D494N	1080:1084	arg1	-IFNα2b					1086:1092	Man-HSA(D494N)-IFNα2b	1072:1092	Man-HSA(D494N)-IFNα2b	1072:1092	These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon.
29688069	1	53	contain	has	270:272	arg1	interferon					242:251	delivering type-I interferon	224:251	delivering type-I interferon to Kupffer cells	224:268	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	1	53	contain	has	270:272	arg2	potential					278:286	the potential to function as a novel type of therapy for the treatment of various types of hepatitis	274:373	the potential to function as a novel type of therapy for the treatment of various types of hepatitis	274:373	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	2	54	theme	N-linked	526:533	arg1	D494N					567:571	D494N	567:571	D494N	567:571	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	54	theme	N-linked	526:533	arg1	chains					551:556	highly mannosylated N-linked oligosaccharide chains	506:556	highly mannosylated N-linked oligosaccharide chains	506:556	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	55	theme	albumin-IFNα2b	462:475	arg1	interferon					447:456	a Kupffer cell targeting type-I interferon	415:456	a Kupffer cell targeting type-I interferon	415:456	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	55	theme	albumin-IFNα2b	462:475	arg1	protein					484:490	an albumin-IFNα2b fusion protein	459:490	an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	459:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	8	56	theme	Kupffer	1546:1552	arg1	interferon					1576:1585	Kupffer cell targeting type-I interferon	1546:1585	Kupffer cell targeting type-I interferon	1546:1585	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	8	57	theme	targeting	1559:1567	arg1	interferon					1576:1585	Kupffer cell targeting type-I interferon	1546:1585	Kupffer cell targeting type-I interferon	1546:1585	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	4	58	theme	significant	849:859	arg1	induction					861:869	a significant induction	847:869	a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	847:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	2	59	contain	contains	497:504	arg1	interferon					447:456	a Kupffer cell targeting type-I interferon	415:456	a Kupffer cell targeting type-I interferon	415:456	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	59	contain	contains	497:504	arg2	D494N					567:571	D494N	567:571	D494N	567:571	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	59	contain	contains	497:504	arg2	chains					551:556	highly mannosylated N-linked oligosaccharide chains	506:556	highly mannosylated N-linked oligosaccharide chains	506:556	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	59	contain	contains	497:504	arg1	protein					484:490	an albumin-IFNα2b fusion protein	459:490	an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	459:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	5	60	theme	type-I	1132:1137	arg1	interferon					1139:1148	type-I interferon	1132:1148	type-I interferon	1132:1148	These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon.
29688069	0	61	theme	interferon	45:54	arg1	Development					0:10	Development	0:10	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.	0:146	Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions.
29688069	8	62	theme	anti-inflammatory	1613:1629	arg1	actions					1652:1658	its anti-inflammatory and immunomodulatory actions	1609:1658	its anti-inflammatory and immunomodulatory actions	1609:1658	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	4	63	theme	IL-1Ra	900:905	arg1	cells					959:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	8	64	theme	proof-of-concept	1465:1480	arg1	study					1482:1486	this proof-of-concept study	1460:1486	this proof-of-concept study	1460:1486	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	8	65	theme	immunomodulatory	1635:1650	arg1	actions					1652:1658	its anti-inflammatory and immunomodulatory actions	1609:1658	its anti-inflammatory and immunomodulatory actions	1609:1658	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	6	66	theme	liver	1197:1201	arg1	injury					1203:1208	liver injury	1197:1208	liver injury	1197:1208	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	6	67	theme	survival	1298:1305	arg1	rate					1307:1310	their survival rate	1292:1310	their survival rate	1292:1310	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	4	68	from	PD-L1	908:912	arg1	cells					926:930	RAW264.7 cells	917:930	RAW264.7 cells	917:930	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	6	69	theme	Concanavalin	1213:1224	arg1	Con-A					1229:1233	Con-A	1229:1233	Con-A	1229:1233	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	6	69	theme	Concanavalin	1213:1224	arg1	A					1226:1226	Concanavalin A	1213:1226	Concanavalin A (Con-A)	1213:1234	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	6	70	theme	hepatitis	1244:1252	arg1	mice					1260:1263	Concanavalin A (Con-A)-induced hepatitis model mice	1213:1263	Concanavalin A (Con-A)-induced hepatitis model mice	1213:1263	Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate.
29688069	1	71	theme	Kupffer	256:262	arg1	cells					264:268	Kupffer cells	256:268	Kupffer cells	256:268	Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis.
29688069	4	72	theme	PD-L1	908:912	arg1	cells					959:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	893:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	3	73	theme	unique	682:687	arg1	oligosaccharide					689:703	this unique oligosaccharide	677:703	this unique oligosaccharide	677:703	The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells.
29688069	4	74	theme	Man-HSA	818:824	arg1	-IFNα2b					832:838	IFNα2b, Man-HSA(D494N)-IFNα2b	810:838	IFNα2b, Man-HSA(D494N)-IFNα2b	810:838	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29688069	2	75	theme	cell	425:428	arg1	interferon					447:456	a Kupffer cell targeting type-I interferon	415:456	a Kupffer cell targeting type-I interferon	415:456	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	75	theme	cell	425:428	arg1	protein					484:490	an albumin-IFNα2b fusion protein	459:490	an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	459:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	76	theme	mannosylated	513:524	arg1	D494N					567:571	D494N	567:571	D494N	567:571	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	76	theme	mannosylated	513:524	arg1	chains					551:556	highly mannosylated N-linked oligosaccharide chains	506:556	highly mannosylated N-linked oligosaccharide chains	506:556	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	3	77	theme	oligosaccharide	689:703	arg1	presence					665:672	The presence	661:672	The presence of this unique oligosaccharide	661:703	The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells.
29688069	2	78	link	N-linked	526:533	arg1	D494N					567:571	D494N	567:571	D494N	567:571	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	78	link	N-linked	526:533	arg1	chains					551:556	highly mannosylated N-linked oligosaccharide chains	506:556	highly mannosylated N-linked oligosaccharide chains	506:556	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	8	79	theme	therapeutic	1505:1515	arg1	effectiveness					1517:1529	therapeutic effectiveness	1505:1529	therapeutic effectiveness	1505:1529	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	2	80	theme	targeting	430:438	arg1	interferon					447:456	a Kupffer cell targeting type-I interferon	415:456	a Kupffer cell targeting type-I interferon	415:456	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	2	80	theme	targeting	430:438	arg1	protein					484:490	an albumin-IFNα2b fusion protein	459:490	an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis	459:658	We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis.
29688069	8	81	dep	effectiveness	1517:1529	arg1	the					1501:1503	the	1501:1503	the	1501:1503	In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.
29688069	4	82	theme	cells	959:963	arg1	levels					883:888	the mRNA levels	874:888	the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells	874:963	Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor.
29070692	13	0	theme	solved	1997:2002	arg1	structure					2004:2012	a recently solved structure	1986:2012	a recently solved structure of another bunyavirus Gc	1986:2037	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	13	1	theme	defined	2089:2095	arg1	specificity					2104:2114	a newly defined family specificity	2081:2114	a newly defined family specificity	2081:2114	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	12	2	theme	protein	1937:1943	arg1	conformation					1945:1956	a typical class II fusion protein conformation	1911:1956	a typical class II fusion protein conformation	1911:1956	The structure displays a typical class II fusion protein conformation.
29070692	4	3	theme	Phenuiviridae	827:839	arg1	family					841:846	the Phenuiviridae family	823:846	the Phenuiviridae family	823:846	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	13	4	with	Comparison	1959:1968	arg1	structure					2004:2012	a recently solved structure	1986:2012	a recently solved structure of another bunyavirus Gc	1986:2037	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	1	5	theme	order	262:266	arg1	Phenuiviridae					247:259	Phenuiviridae	247:259	Phenuiviridae	247:259	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	5	theme	order	262:266	arg1	glycoproteins					313:325	two viral surface glycoproteins	295:325	two viral surface glycoproteins encoded by the M segment	295:350	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	5	theme	order	262:266	arg1	Gc					288:289	Gc	288:289	Gc	288:289	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	5	theme	order	262:266	arg1	Gn					281:282	order Bunyavirales Gn	262:282	order Bunyavirales Gn	262:282	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	9	6	theme	M	1655:1655	arg1	segment					1657:1663	The M segment	1651:1663	The M segment of the virus	1651:1676	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	9	6	theme	M	1655:1655	arg1	precursor					1700:1708	a polyprotein precursor	1686:1708	a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc	1686:1758	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	6	7	theme	fusogenic	1151:1159	arg1	process					1161:1167	the fusogenic process	1147:1167	the fusogenic process	1147:1167	This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses.
29070692	13	8	theme	recent	2132:2137	arg1	Committee					2153:2161	the recent International Committee	2128:2161	the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses	2128:2221	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	12	9	theme	typical	1913:1919	arg1	conformation					1945:1956	a typical class II fusion protein conformation	1911:1956	a typical class II fusion protein conformation	1911:1956	The structure displays a typical class II fusion protein conformation.
29070692	7	10	theme	human	1416:1420	arg1	HRTV					1443:1446	these human pathogens.IMPORTANCE HRTV	1410:1446	these human pathogens.IMPORTANCE HRTV	1410:1446	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	14	11	theme	bunyavirus	2313:2322	arg1	characterizations					2324:2340	bunyavirus characterizations	2313:2340	bunyavirus characterizations	2313:2340	Our results expand the knowledge of bunyavirus fusion proteins and help us to understand bunyavirus characterizations.
29070692	1	12	theme	emerging	182:189	arg1	pathogen					197:204	an emerging human pathogen	179:204	an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection	179:401	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	12	theme	emerging	182:189	arg1	virus					163:167	Heartland virus	153:167	Heartland virus (HRTV)	153:174	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	5	13	attach	presents	915:922	arg2	Gc					912:913	the hantavirus Gc	897:913	the hantavirus Gc	897:913	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	5	13	attach	presents	915:922	arg1	aspects					949:955	the aspects	945:955	the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation	945:1081	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	9	14	theme	virus	1672:1676	arg1	segment					1657:1663	The M segment	1651:1663	The M segment of the virus	1651:1676	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	9	14	theme	virus	1672:1676	arg1	precursor					1700:1708	a polyprotein precursor	1686:1708	a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc	1686:1758	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	7	15	from	comparison	1281:1290	arg1	families					1347:1354	two bunyavirus families	1332:1354	two bunyavirus families	1332:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	6	16	theme	subunit	1120:1126	arg1	arrangement					1128:1138	their family-specific subunit arrangement	1098:1138	their family-specific subunit arrangement during the fusogenic process	1098:1167	This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses.
29070692	13	17	theme	Gc	2059:2060	arg1	structures					2062:2071	these Gc structures	2053:2071	these Gc structures	2053:2071	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	5	18	link	N-linked	983:990	arg1	glycosylation					992:1004	N-linked glycosylation	983:1004	N-linked glycosylation	983:1004	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	1	19	theme	early	373:377	arg1	events					379:384	early events	373:384	early events during infection	373:401	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	3	20	theme	HRTV	572:575	arg1	Gc					577:578	HRTV Gc	572:578	HRTV Gc	572:578	Here, we describe the crystal structure of HRTV Gc in its postfusion conformation.
29070692	7	21	theme	valuable	1366:1373	arg1	information					1375:1385	valuable information	1366:1385	valuable information for treatments against these human pathogens.IMPORTANCE HRTV	1366:1446	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	7	21	theme	valuable	1366:1373	arg1	virus					1467:1471	an insect-borne virus	1451:1471	an insect-borne virus found in America that can infect humans	1451:1511	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	4	22	theme	protein	675:681	arg1	conformation					683:694	a typical class II fusion protein conformation	649:694	a typical class II fusion protein conformation	649:694	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	13	23	theme	Gc	2036:2037	arg1	structure					2004:2012	a recently solved structure	1986:2012	a recently solved structure of another bunyavirus Gc	1986:2037	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	5	24	theme	structural	862:871	arg1	analysis					873:880	our structural analysis	858:880	our structural analysis	858:880	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	6	25	theme	taxonomic	1193:1201	arg1	revision					1203:1210	the recent taxonomic revision	1182:1210	the recent taxonomic revision of bunyaviruses	1182:1226	This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses.
29070692	8	26	contain	contains	1592:1599	arg2	S					1647:1647	S	1647:1647	S	1647:1647	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	26	contain	contains	1592:1599	arg2	M					1640:1640	M	1640:1640	M	1640:1640	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	26	contain	contains	1592:1599	arg2	L					1637:1637	L	1637:1637	L	1637:1637	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	26	contain	contains	1592:1599	arg2	segments					1627:1634	three single-stranded RNA segments	1601:1634	three single-stranded RNA segments (L, M, and S)	1601:1648	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	26	contain	contains	1592:1599	arg1	HRTV					1587:1590	order Bunyavirales HRTV	1568:1590	order Bunyavirales HRTV	1568:1590	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	5	27	theme	interaction	1011:1021	arg1	pattern					1023:1029	the interaction pattern	1007:1029	the interaction pattern between protomers	1007:1047	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	3	28	theme	postfusion	587:596	arg1	conformation					598:609	its postfusion conformation	583:609	its postfusion conformation	583:609	Here, we describe the crystal structure of HRTV Gc in its postfusion conformation.
29070692	2	29	theme	envelope	471:478	arg1	fusion					451:456	fusion	451:456	fusion of the viral envelope	451:478	HRTV delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-pH conditions.
29070692	7	30	theme	bunyavirus	1336:1345	arg1	families					1347:1354	two bunyavirus families	1332:1354	two bunyavirus families	1332:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	4	31	theme	typical	651:657	arg1	conformation					683:694	a typical class II fusion protein conformation	649:694	a typical class II fusion protein conformation	649:694	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	0	32	theme	Glycoprotein	51:62	arg1	Structure					15:23	The Postfusion Structure	0:23	The Postfusion Structure of the Heartland Virus Gc Glycoprotein	0:62	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	15	33	theme	bunyavirus	2430:2439	arg1	infections					2441:2450	bunyavirus infections	2430:2450	bunyavirus infections	2430:2450	This study provides useful information to improve protection against and therapies for bunyavirus infections.
29070692	13	34	theme	bunyaviruses	2210:2221	arg1	reclassification					2186:2201	Taxonomy of Viruses reclassification	2166:2201	Taxonomy of Viruses reclassification of the bunyaviruses	2166:2221	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	14	35	theme	fusion	2271:2276	arg1	proteins					2278:2285	bunyavirus fusion proteins	2260:2285	bunyavirus fusion proteins	2260:2285	Our results expand the knowledge of bunyavirus fusion proteins and help us to understand bunyavirus characterizations.
29070692	0	36	theme	Taxonomic	73:81	arg1	Separation					83:92	Taxonomic Separation	73:92	Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae	73:150	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	10	37	theme	virus	1797:1801	arg1	entry					1803:1807	virus entry	1797:1807	virus entry into host cells	1797:1823	Gc is a fusion protein facilitating virus entry into host cells.
29070692	1	38	theme	M	342:342	arg1	segment					344:350	the M segment	338:350	the M segment	338:350	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	5	39	theme	distinct	924:931	arg1	features					933:940	distinct features	924:940	distinct features	924:940	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	2	40	theme	endosomal	484:492	arg1	membranes					494:502	endosomal membranes	484:502	endosomal membranes	484:502	HRTV delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-pH conditions.
29070692	4	41	theme	severe	739:744	arg1	fever					746:750	severe fever	739:750	severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family	739:846	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	0	42	theme	Bunyaviral	101:110	arg1	Hantaviridae					139:150	Hantaviridae	139:150	Hantaviridae	139:150	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	0	42	theme	Bunyaviral	101:110	arg1	Phenuiviridae					121:133	Phenuiviridae	121:133	Phenuiviridae	121:133	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	0	42	theme	Bunyaviral	101:110	arg1	Families					112:119	the Bunyaviral Families	97:119	the Bunyaviral Families Phenuiviridae and Hantaviridae	97:150	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	8	43	dep	segments	1627:1634	arg1	M					1640:1640	M	1640:1640	M	1640:1640	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	43	dep	segments	1627:1634	arg1	S					1647:1647	S	1647:1647	S	1647:1647	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	43	dep	segments	1627:1634	arg1	L					1637:1637	L	1637:1637	L	1637:1637	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	43	dep	segments	1627:1634	arg1	segments					1627:1634	three single-stranded RNA segments	1601:1634	three single-stranded RNA segments (L, M, and S)	1601:1648	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	44	theme	defined	1538:1544	arg1	Phenuiviridae					1553:1565	the newly defined family Phenuiviridae	1528:1565	the newly defined family Phenuiviridae	1528:1565	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	1	45	theme	Bunyavirales	268:279	arg1	Phenuiviridae					247:259	Phenuiviridae	247:259	Phenuiviridae	247:259	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	45	theme	Bunyavirales	268:279	arg1	glycoproteins					313:325	two viral surface glycoproteins	295:325	two viral surface glycoproteins encoded by the M segment	295:350	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	45	theme	Bunyavirales	268:279	arg1	Gc					288:289	Gc	288:289	Gc	288:289	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	45	theme	Bunyavirales	268:279	arg1	Gn					281:282	order Bunyavirales Gn	262:282	order Bunyavirales Gn	262:282	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	7	46	theme	proteins	1320:1327	arg1	comparison					1281:1290	the comprehensive comparison	1263:1290	the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families	1263:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	3	47	from	structure	559:567	arg1	conformation					598:609	its postfusion conformation	583:609	its postfusion conformation	583:609	Here, we describe the crystal structure of HRTV Gc in its postfusion conformation.
29070692	11	48	theme	Gc	1876:1877	arg1	protein					1879:1885	the HRTV Gc protein	1867:1885	the HRTV Gc protein	1867:1885	Here, we report the crystal structure of the HRTV Gc protein.
29070692	7	49	theme	membrane	1304:1311	arg1	proteins					1320:1327	class II membrane fusion proteins	1295:1327	class II membrane fusion proteins in two bunyavirus families	1295:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	8	50	theme	order	1568:1572	arg1	HRTV					1587:1590	order Bunyavirales HRTV	1568:1590	order Bunyavirales HRTV	1568:1590	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	13	51	theme	International	2139:2151	arg1	Committee					2153:2161	the recent International Committee	2128:2161	the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses	2128:2221	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	7	52	theme	class	1295:1299	arg1	proteins					1320:1327	class II membrane fusion proteins	1295:1327	class II membrane fusion proteins in two bunyavirus families	1295:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	0	53	theme	Virus	42:46	arg1	Glycoprotein					51:62	the Heartland Virus Gc Glycoprotein	28:62	the Heartland Virus Gc Glycoprotein	28:62	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	1	54	theme	viral	299:303	arg1	Phenuiviridae					247:259	Phenuiviridae	247:259	Phenuiviridae	247:259	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	54	theme	viral	299:303	arg1	glycoproteins					313:325	two viral surface glycoproteins	295:325	two viral surface glycoproteins encoded by the M segment	295:350	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	54	theme	viral	299:303	arg1	Gc					288:289	Gc	288:289	Gc	288:289	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	54	theme	viral	299:303	arg1	Gn					281:282	order Bunyavirales Gn	262:282	order Bunyavirales Gn	262:282	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	5	55	theme	glycosylation	992:1004	arg1	aspects					949:955	the aspects	945:955	the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation	945:1081	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	13	56	theme	Gc	1978:1979	arg1	Comparison					1959:1968	Comparison	1959:1968	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc	1959:2037	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	8	57	theme	RNA	1623:1625	arg1	M					1640:1640	M	1640:1640	M	1640:1640	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	57	theme	RNA	1623:1625	arg1	S					1647:1647	S	1647:1647	S	1647:1647	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	57	theme	RNA	1623:1625	arg1	L					1637:1637	L	1637:1637	L	1637:1637	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	57	theme	RNA	1623:1625	arg1	segments					1627:1634	three single-stranded RNA segments	1601:1634	three single-stranded RNA segments (L, M, and S)	1601:1648	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	4	58	theme	syndrome	774:781	arg1	SFTSV					790:794	SFTSV	790:794	SFTSV	790:794	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	4	58	theme	syndrome	774:781	arg1	virus					783:787	thrombocytopenia syndrome virus	757:787	thrombocytopenia syndrome virus (SFTSV) Gc	757:798	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	5	59	theme	subdomain	960:968	arg1	orientation					970:980	subdomain orientation	960:980	subdomain orientation	960:980	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	13	60	theme	family	2097:2102	arg1	specificity					2104:2114	a newly defined family specificity	2081:2114	a newly defined family specificity	2081:2114	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	12	61	theme	fusion	1930:1935	arg1	conformation					1945:1956	a typical class II fusion protein conformation	1911:1956	a typical class II fusion protein conformation	1911:1956	The structure displays a typical class II fusion protein conformation.
29070692	7	62	theme	insect-borne	1454:1465	arg1	information					1375:1385	valuable information	1366:1385	valuable information for treatments against these human pathogens.IMPORTANCE HRTV	1366:1446	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	7	62	theme	insect-borne	1454:1465	arg1	virus					1467:1471	an insect-borne virus	1451:1471	an insect-borne virus found in America that can infect humans	1451:1511	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	1	63	gly	glycoproteins	313:325	arg1	Phenuiviridae					247:259	Phenuiviridae	247:259	Phenuiviridae	247:259	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	63	gly	glycoproteins	313:325	arg1	glycoproteins					313:325	two viral surface glycoproteins	295:325	two viral surface glycoproteins encoded by the M segment	295:350	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	63	gly	glycoproteins	313:325	arg1	Gc					288:289	Gc	288:289	Gc	288:289	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	63	gly	glycoproteins	313:325	arg1	Gn					281:282	order Bunyavirales Gn	262:282	order Bunyavirales Gn	262:282	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	7	64	theme	pathogens.IMPORTANCE	1422:1441	arg1	HRTV					1443:1446	these human pathogens.IMPORTANCE HRTV	1410:1446	these human pathogens.IMPORTANCE HRTV	1410:1446	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	1	65	theme	human	191:195	arg1	pathogen					197:204	an emerging human pathogen	179:204	an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection	179:401	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	65	theme	human	191:195	arg1	virus					163:167	Heartland virus	153:167	Heartland virus (HRTV)	153:174	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	12	66	theme	class	1921:1925	arg1	conformation					1945:1956	a typical class II fusion protein conformation	1911:1956	a typical class II fusion protein conformation	1911:1956	The structure displays a typical class II fusion protein conformation.
29070692	6	67	theme	family-specific	1104:1118	arg1	arrangement					1128:1138	their family-specific subunit arrangement	1098:1138	their family-specific subunit arrangement during the fusogenic process	1098:1167	This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses.
29070692	15	68	theme	useful	2363:2368	arg1	information					2370:2380	useful information	2363:2380	useful information to improve protection against and therapies for bunyavirus infections	2363:2450	This study provides useful information to improve protection against and therapies for bunyavirus infections.
29070692	10	69	theme	fusion	1769:1774	arg1	Gc					1761:1762	Gc	1761:1762	Gc	1761:1762	Gc is a fusion protein facilitating virus entry into host cells.
29070692	10	69	theme	fusion	1769:1774	arg1	protein					1776:1782	a fusion protein	1767:1782	a fusion protein facilitating virus entry into host cells	1767:1823	Gc is a fusion protein facilitating virus entry into host cells.
29070692	2	70	theme	low-pH	510:515	arg1	conditions					517:526	low-pH conditions	510:526	low-pH conditions	510:526	HRTV delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-pH conditions.
29070692	6	71	theme	bunyaviruses	1215:1226	arg1	revision					1203:1210	the recent taxonomic revision	1182:1210	the recent taxonomic revision of bunyaviruses	1182:1226	This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses.
29070692	13	72	theme	Taxonomy	2166:2173	arg1	reclassification					2186:2201	Taxonomy of Viruses reclassification	2166:2201	Taxonomy of Viruses reclassification of the bunyaviruses	2166:2221	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	3	73	theme	crystal	551:557	arg1	structure					559:567	the crystal structure	547:567	the crystal structure of HRTV Gc in its postfusion conformation	547:609	Here, we describe the crystal structure of HRTV Gc in its postfusion conformation.
29070692	4	74	theme	fusion	668:673	arg1	conformation					683:694	a typical class II fusion protein conformation	649:694	a typical class II fusion protein conformation	649:694	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	9	75	gly	glycoproteins	1735:1747	arg1	glycoproteins					1735:1747	two glycoproteins	1731:1747	two glycoproteins	1731:1747	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	9	75	gly	glycoproteins	1735:1747	arg1	Gc					1757:1758	Gc	1757:1758	Gc	1757:1758	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	9	75	gly	glycoproteins	1735:1747	arg1	Gn					1750:1751	Gn	1750:1751	Gn	1750:1751	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	7	76	located	found	1473:1477	arg2	virus					1467:1471	an insect-borne virus	1451:1471	an insect-borne virus found in America that can infect humans	1451:1511	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	7	76	located	found	1473:1477	arg2	information					1375:1385	valuable information	1366:1385	valuable information for treatments against these human pathogens.IMPORTANCE HRTV	1366:1446	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	7	76	located	found	1473:1477	arg1	America					1482:1488	America	1482:1488	America	1482:1488	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	1	77	dep	family	240:245	arg1	Phenuiviridae					247:259	Phenuiviridae	247:259	Phenuiviridae	247:259	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	77	dep	family	240:245	arg1	required					360:367	required	360:367	are required for early events during infection	356:401	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	77	dep	family	240:245	arg1	Gc					288:289	Gc	288:289	Gc	288:289	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	77	dep	family	240:245	arg1	glycoproteins					313:325	two viral surface glycoproteins	295:325	two viral surface glycoproteins encoded by the M segment	295:350	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	77	dep	family	240:245	arg1	Gn					281:282	order Bunyavirales Gn	262:282	order Bunyavirales Gn	262:282	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	6	78	theme	recent	1186:1191	arg1	revision					1203:1210	the recent taxonomic revision	1182:1210	the recent taxonomic revision of bunyaviruses	1182:1226	This suggests their family-specific subunit arrangement during the fusogenic process and supports the recent taxonomic revision of bunyaviruses.
29070692	5	79	theme	pattern	1023:1029	arg1	aspects					949:955	the aspects	945:955	the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation	945:1081	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	3	80	theme	Gc	577:578	arg1	structure					559:567	the crystal structure	547:567	the crystal structure of HRTV Gc in its postfusion conformation	547:609	Here, we describe the crystal structure of HRTV Gc in its postfusion conformation.
29070692	1	81	theme	Heartland	153:161	arg1	pathogen					197:204	an emerging human pathogen	179:204	an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection	179:401	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	81	theme	Heartland	153:161	arg1	virus					163:167	Heartland virus	153:167	Heartland virus (HRTV)	153:174	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	81	theme	Heartland	153:161	arg1	HRTV					170:173	HRTV	170:173	HRTV	170:173	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	2	82	theme	viral	465:469	arg1	envelope					471:478	the viral envelope	461:478	the viral envelope	461:478	HRTV delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-pH conditions.
29070692	14	83	theme	proteins	2278:2285	arg1	knowledge					2247:2255	the knowledge	2243:2255	the knowledge of bunyavirus fusion proteins	2243:2285	Our results expand the knowledge of bunyavirus fusion proteins and help us to understand bunyavirus characterizations.
29070692	4	84	theme	class	659:663	arg1	conformation					683:694	a typical class II fusion protein conformation	649:694	a typical class II fusion protein conformation	649:694	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	14	85	theme	bunyavirus	2260:2269	arg1	proteins					2278:2285	bunyavirus fusion proteins	2260:2285	bunyavirus fusion proteins	2260:2285	Our results expand the knowledge of bunyavirus fusion proteins and help us to understand bunyavirus characterizations.
29070692	13	86	theme	bunyavirus	2025:2034	arg1	Gc					2036:2037	another bunyavirus Gc	2017:2037	another bunyavirus Gc	2017:2037	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	0	87	dep	Families	112:119	arg1	Hantaviridae					139:150	Hantaviridae	139:150	Hantaviridae	139:150	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	0	87	dep	Families	112:119	arg1	Phenuiviridae					121:133	Phenuiviridae	121:133	Phenuiviridae	121:133	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	0	87	dep	Families	112:119	arg1	Families					112:119	the Bunyaviral Families	97:119	the Bunyaviral Families Phenuiviridae and Hantaviridae	97:150	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	13	88	from	Committee	2153:2161	arg1	reclassification					2186:2201	Taxonomy of Viruses reclassification	2166:2201	Taxonomy of Viruses reclassification of the bunyaviruses	2166:2221	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	4	89	with	fever	746:750	arg1	Gc					797:798	thrombocytopenia syndrome virus (SFTSV) Gc	757:798	thrombocytopenia syndrome virus (SFTSV) Gc	757:798	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	0	90	theme	Families	112:119	arg1	Separation					83:92	Taxonomic Separation	73:92	Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae	73:150	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	5	91	theme	fusion	1058:1063	arg1	conformation					1070:1081	the fusion loop conformation	1054:1081	the fusion loop conformation	1054:1081	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	7	92	from	families	1347:1354	arg1	comparison					1281:1290	the comprehensive comparison	1263:1290	the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families	1263:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	8	93	theme	family	1546:1551	arg1	Phenuiviridae					1553:1565	the newly defined family Phenuiviridae	1528:1565	the newly defined family Phenuiviridae	1528:1565	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	0	94	theme	Postfusion	4:13	arg1	Structure					15:23	The Postfusion Structure	0:23	The Postfusion Structure of the Heartland Virus Gc Glycoprotein	0:62	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	5	95	theme	conformation	1070:1081	arg1	aspects					949:955	the aspects	945:955	the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation	945:1081	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	7	96	theme	fusion	1313:1318	arg1	proteins					1320:1327	class II membrane fusion proteins	1295:1327	class II membrane fusion proteins in two bunyavirus families	1295:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	11	97	theme	crystal	1846:1852	arg1	structure					1854:1862	the crystal structure	1842:1862	the crystal structure of the HRTV Gc protein	1842:1885	Here, we report the crystal structure of the HRTV Gc protein.
29070692	13	98	theme	Viruses	2178:2184	arg1	Taxonomy					2166:2173	Taxonomy	2166:2173	Taxonomy of Viruses reclassification of the bunyaviruses	2166:2221	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	5	99	theme	hantavirus	901:910	arg1	Gc					912:913	the hantavirus Gc	897:913	the hantavirus Gc	897:913	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	7	100	theme	II	1301:1302	arg1	proteins					1320:1327	class II membrane fusion proteins	1295:1327	class II membrane fusion proteins in two bunyavirus families	1295:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	8	101	theme	Bunyavirales	1574:1585	arg1	HRTV					1587:1590	order Bunyavirales HRTV	1568:1590	order Bunyavirales HRTV	1568:1590	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	4	102	theme	overall	705:711	arg1	identical					726:734	identical	726:734	identical	726:734	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	4	102	theme	overall	705:711	arg1	structure					713:721	the overall structure	701:721	the overall structure	701:721	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	11	103	theme	protein	1879:1885	arg1	structure					1854:1862	the crystal structure	1842:1862	the crystal structure of the HRTV Gc protein	1842:1885	Here, we report the crystal structure of the HRTV Gc protein.
29070692	0	104	theme	Heartland	32:40	arg1	Glycoprotein					51:62	the Heartland Virus Gc Glycoprotein	28:62	the Heartland Virus Gc Glycoprotein	28:62	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	5	105	theme	orientation	970:980	arg1	aspects					949:955	the aspects	945:955	the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation	945:1081	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	10	106	theme	host	1814:1817	arg1	cells					1819:1823	host cells	1814:1823	host cells	1814:1823	Gc is a fusion protein facilitating virus entry into host cells.
29070692	4	107	theme	virus	783:787	arg1	Gc					797:798	thrombocytopenia syndrome virus (SFTSV) Gc	757:798	thrombocytopenia syndrome virus (SFTSV) Gc	757:798	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	11	108	theme	HRTV	1871:1874	arg1	protein					1879:1885	the HRTV Gc protein	1867:1885	the HRTV Gc protein	1867:1885	Here, we report the crystal structure of the HRTV Gc protein.
29070692	0	109	theme	Gc	48:49	arg1	Glycoprotein					51:62	the Heartland Virus Gc Glycoprotein	28:62	the Heartland Virus Gc Glycoprotein	28:62	The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
29070692	5	110	theme	N-linked	983:990	arg1	glycosylation					992:1004	N-linked glycosylation	983:1004	N-linked glycosylation	983:1004	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	5	111	theme	loop	1065:1068	arg1	conformation					1070:1081	the fusion loop conformation	1054:1081	the fusion loop conformation	1054:1081	However, our structural analysis indicates that the hantavirus Gc presents distinct features in the aspects of subdomain orientation, N-linked glycosylation, the interaction pattern between protomers, and the fusion loop conformation.
29070692	7	112	theme	comprehensive	1267:1279	arg1	comparison					1281:1290	the comprehensive comparison	1263:1290	the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families	1263:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	9	113	theme	polyprotein	1688:1698	arg1	segment					1657:1663	The M segment	1651:1663	The M segment of the virus	1651:1676	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	9	113	theme	polyprotein	1688:1698	arg1	precursor					1700:1708	a polyprotein precursor	1686:1708	a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc	1686:1758	The M segment of the virus encodes a polyprotein precursor that is cleaved into two glycoproteins, Gn and Gc.
29070692	8	114	theme	single-stranded	1607:1621	arg1	M					1640:1640	M	1640:1640	M	1640:1640	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	114	theme	single-stranded	1607:1621	arg1	S					1647:1647	S	1647:1647	S	1647:1647	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	114	theme	single-stranded	1607:1621	arg1	L					1637:1637	L	1637:1637	L	1637:1637	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	8	114	theme	single-stranded	1607:1621	arg1	segments					1627:1634	three single-stranded RNA segments	1601:1634	three single-stranded RNA segments (L, M, and S)	1601:1648	It belongs to the newly defined family Phenuiviridae, order Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S).
29070692	13	115	theme	HRTV	1973:1976	arg1	Gc					1978:1979	HRTV Gc	1973:1979	HRTV Gc	1973:1979	Comparison of HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that these Gc structures display a newly defined family specificity, supporting the recent International Committee on Taxonomy of Viruses reclassification of the bunyaviruses.
29070692	1	116	theme	surface	305:311	arg1	Phenuiviridae					247:259	Phenuiviridae	247:259	Phenuiviridae	247:259	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	116	theme	surface	305:311	arg1	glycoproteins					313:325	two viral surface glycoproteins	295:325	two viral surface glycoproteins encoded by the M segment	295:350	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	116	theme	surface	305:311	arg1	Gc					288:289	Gc	288:289	Gc	288:289	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	1	116	theme	surface	305:311	arg1	Gn					281:282	order Bunyavirales Gn	262:282	order Bunyavirales Gn	262:282	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
29070692	7	117	from	proteins	1320:1327	arg1	families					1347:1354	two bunyavirus families	1332:1354	two bunyavirus families	1332:1354	Our results provide insights into the comprehensive comparison of class II membrane fusion proteins in two bunyavirus families, yielding valuable information for treatments against these human pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can infect humans.
29070692	4	118	theme	thrombocytopenia	757:772	arg1	SFTSV					790:794	SFTSV	790:794	SFTSV	790:794	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	4	118	theme	thrombocytopenia	757:772	arg1	virus					783:787	thrombocytopenia syndrome virus	757:787	thrombocytopenia syndrome virus (SFTSV) Gc	757:798	The structure shows that Gc displays a typical class II fusion protein conformation, and the overall structure is identical to severe fever with thrombocytopenia syndrome virus (SFTSV) Gc, which also belongs to the Phenuiviridae family.
29070692	1	119	theme	defined	232:238	arg1	family					240:245	the newly defined family	222:245	the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection	222:401	Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface glycoproteins encoded by the M segment and are required for early events during infection.
28474843	14	0	theme	unrecognized	1790:1801	arg1	role					1803:1806	a previously unrecognized role	1777:1806	a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions	1777:1885	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	8	1	theme	glycans	1044:1050	arg1	hybrid-types					1028:1039	complex hybrid-types	1020:1039	complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc)	1020:1128	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	11	2	theme	DC-SIGN	1490:1496	arg1	expression					1476:1485	the expression	1472:1485	the expression of DC-SIGN and DCIR	1472:1505	An analysis of CLRs revealed the expression of DC-SIGN and DCIR, but not MRC1 and dectin-1, in human basophils.
28474843	8	3	theme	MALDI-TOF	950:958	arg1	analysis					979:986	MALDI-TOF mass spectrometric analysis	950:986	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2	942:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	2	4	theme	allergen-induced	288:303	arg1	allergy					305:311	cockroach allergen-induced allergy	278:311	cockroach allergen-induced allergy	278:311	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	4	5	from	g	520:520	arg1	glycans					465:471	METHODS N-linked glycans	448:471	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2	448:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	8	6	dep	RESULTS	942:948	arg1	analysis					979:986	MALDI-TOF mass spectrometric analysis	950:986	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2	942:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	14	7	from	function	1963:1970	arg1	regulation					1930:1939	the regulation	1926:1939	the regulation of glycan on basophil function	1926:1970	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	14	8	theme	basophil	1954:1961	arg1	function					1963:1970	basophil function	1954:1970	basophil function	1954:1970	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	4	9	theme	purified	488:495	arg1	g					520:520	naturally purified cockroach allergen Bla g 2	478:522	naturally purified cockroach allergen Bla g 2	478:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	6	10	theme	glycan	732:737	arg1	Role					703:706	Role	703:706	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils	703:799	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	5	11	theme	allergen	596:603	arg1	Binding					575:581	Binding	575:581	Binding of cockroach allergen to serum IgE from cockroach allergic subjects	575:649	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	14	12	theme	glycan	1944:1949	arg1	regulation					1930:1939	the regulation	1926:1939	the regulation of glycan on basophil function	1926:1970	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	12	13	theme	Bla	1627:1629	arg1	uptake					1635:1640	Bla g 2 uptake	1627:1640	Bla g 2 uptake by human basophils	1627:1659	Neutralizing antibody to DCIR, but not DC-SIGN, significantly inhibited Bla g 2 uptake by human basophils.
28474843	4	14	theme	allergen	507:514	arg1	g					520:520	naturally purified cockroach allergen Bla g 2	478:522	naturally purified cockroach allergen Bla g 2	478:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	5	15	theme	serum	608:612	arg1	IgE					614:616	serum IgE	608:616	serum IgE from cockroach allergic subjects	608:649	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	5	16	from	subjects	642:649	arg1	IgE					614:616	serum IgE	608:616	serum IgE from cockroach allergic subjects	608:649	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	4	17	theme	N-linked	456:463	arg1	glycans					465:471	METHODS N-linked glycans	448:471	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2	448:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	10	18	from	basophils	1367:1375	arg1	release					1334:1340	histamine release	1324:1340	histamine release	1324:1340	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	10	18	from	basophils	1367:1375	arg1	production					1351:1360	IL-4 production	1346:1360	IL-4 production	1346:1360	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	6	19	theme	associated	721:730	arg1	glycan					732:737	cockroach associated glycan	711:737	cockroach associated glycan	711:737	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	1	20	theme	increased	152:160	arg1	risk					162:165	an increased risk	149:165	an increased risk for asthma	149:176	INTRODUCTION Cockroach allergen exposure elicits cockroach sensitization and poses an increased risk for asthma.
28474843	8	21	from	analysis	979:986	arg1	g					1009:1009	Bla g 2	1005:1011	Bla g 2	1005:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	9	22	from	basophils	1246:1254	arg1	release					1227:1233	histamine release	1217:1233	histamine release from human basophils	1217:1254	Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils.
28474843	10	23	theme	Bla	1292:1294	arg1	g					1296:1296	Bla g 2	1292:1298	Bla g 2	1292:1298	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	14	24	from	DCIR	1892:1895	arg1	reactions					1877:1885	allergen-induced immune reactions	1853:1885	allergen-induced immune reactions	1853:1885	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	0	25	from	N-glycan	0:7	arg1	allergen					22:29	cockroach allergen	12:29	cockroach allergen	12:29	N-glycan in cockroach allergen regulates human basophil function.
28474843	9	26	theme	Deglycosylated	1131:1144	arg1	g					1150:1150	Deglycosylated Bla g 2	1131:1152	Deglycosylated Bla g 2	1131:1152	Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils.
28474843	1	27	theme	INTRODUCTION	66:77	arg1	exposure					98:105	INTRODUCTION Cockroach allergen exposure	66:105	INTRODUCTION Cockroach allergen exposure	66:105	INTRODUCTION Cockroach allergen exposure elicits cockroach sensitization and poses an increased risk for asthma.
28474843	4	28	link	N-linked	456:463	arg1	glycans					465:471	METHODS N-linked glycans	448:471	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2	448:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	10	29	theme	IL-4	1346:1349	arg1	production					1351:1360	IL-4 production	1346:1360	IL-4 production	1346:1360	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	1	30	theme	allergen	89:96	arg1	exposure					98:105	INTRODUCTION Cockroach allergen exposure	66:105	INTRODUCTION Cockroach allergen exposure	66:105	INTRODUCTION Cockroach allergen exposure elicits cockroach sensitization and poses an increased risk for asthma.
28474843	8	31	theme	mass	960:963	arg1	analysis					979:986	MALDI-TOF mass spectrometric analysis	950:986	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2	942:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	8	32	from	g	1009:1009	arg1	analysis					979:986	MALDI-TOF mass spectrometric analysis	950:986	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2	942:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	8	32	from	g	1009:1009	arg1	N-glycan					991:998	N-glycan	991:998	N-glycan from Bla g 2	991:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	6	33	theme	IL-4	764:767	arg1	production					769:778	IL-4 production	764:778	IL-4 production	764:778	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	5	34	theme	allergic	633:640	arg1	subjects					642:649	cockroach allergic subjects	623:649	cockroach allergic subjects	623:649	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	3	35	theme	glycan	402:407	arg1	role					373:376	the role	369:376	the role of cockroach-associated glycan in regulating human basophil function	369:445	We sought to examine the role of cockroach-associated glycan in regulating human basophil function.
28474843	6	36	from	Role	703:706	arg1	release					752:758	histamine release	742:758	histamine release	742:758	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	6	36	from	Role	703:706	arg1	production					769:778	IL-4 production	764:778	IL-4 production	764:778	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	6	36	from	Role	703:706	arg1	basophils					791:799	human basophils	785:799	human basophils	785:799	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	13	37	theme	cockroach	1691:1699	arg1	allergen					1701:1708	cockroach allergen	1691:1708	cockroach allergen	1691:1708	A dose-dependent bindings of cockroach allergen to DCIR was also observed.
28474843	0	38	theme	cockroach	12:20	arg1	allergen					22:29	cockroach allergen	12:29	cockroach allergen	12:29	N-glycan in cockroach allergen regulates human basophil function.
28474843	12	39	theme	Neutralizing	1555:1566	arg1	antibody					1568:1575	Neutralizing antibody	1555:1575	Neutralizing antibody to DCIR, but not DC-SIGN,	1555:1601	Neutralizing antibody to DCIR, but not DC-SIGN, significantly inhibited Bla g 2 uptake by human basophils.
28474843	8	40	theme	N-glycan	991:998	arg1	analysis					979:986	MALDI-TOF mass spectrometric analysis	950:986	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2	942:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	8	41	theme	Bla	1005:1007	arg1	g					1009:1009	Bla g 2	1005:1011	Bla g 2	1005:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	3	42	theme	basophil	429:436	arg1	function					438:445	human basophil function	423:445	human basophil function	423:445	We sought to examine the role of cockroach-associated glycan in regulating human basophil function.
28474843	0	43	theme	basophil	47:54	arg1	function					56:63	human basophil function	41:63	human basophil function	41:63	N-glycan in cockroach allergen regulates human basophil function.
28474843	7	44	theme	receptors	843:851	arg1	role					870:873	their role	864:873	their role in mediating glycan-uptake in the basophils	864:917	Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated.
28474843	7	44	theme	receptors	843:851	arg1	Expression					815:824	Expression	815:824	Expression of C-type lectin receptors (CLRs)	815:858	Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated.
28474843	2	45	theme	cockroach	212:220	arg1	allergen					222:229	cockroach allergen	212:229	cockroach allergen	212:229	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	7	46	theme	C-type	829:834	arg1	CLRs					854:857	CLRs	854:857	CLRs	854:857	Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated.
28474843	7	46	theme	C-type	829:834	arg1	receptors					843:851	C-type lectin receptors	829:851	C-type lectin receptors (CLRs)	829:858	Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated.
28474843	11	47	theme	DCIR	1502:1505	arg1	expression					1476:1485	the expression	1472:1485	the expression of DC-SIGN and DCIR	1472:1505	An analysis of CLRs revealed the expression of DC-SIGN and DCIR, but not MRC1 and dectin-1, in human basophils.
28474843	8	48	theme	complex	1020:1026	arg1	hybrid-types					1028:1039	complex hybrid-types	1020:1039	complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc)	1020:1128	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	11	49	theme	CLRs	1458:1461	arg1	analysis					1446:1453	An analysis	1443:1453	An analysis of CLRs	1443:1461	An analysis of CLRs revealed the expression of DC-SIGN and DCIR, but not MRC1 and dectin-1, in human basophils.
28474843	14	50	from	regulation	1930:1939	arg1	function					1963:1970	basophil function	1954:1970	basophil function	1954:1970	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	14	51	theme	cockroach	1812:1820	arg1	glycans					1842:1848	cockroach allergen-associated glycans	1812:1848	cockroach allergen-associated glycans	1812:1848	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	6	52	from	basophils	791:799	arg1	release					752:758	histamine release	742:758	histamine release	742:758	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	6	52	from	basophils	791:799	arg1	production					769:778	IL-4 production	764:778	IL-4 production	764:778	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	6	52	from	basophils	791:799	arg1	Role					703:706	Role	703:706	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils	703:799	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	10	53	theme	allergic	1424:1431	arg1	subjects					1433:1440	cockroach allergic subjects	1414:1440	cockroach allergic subjects	1414:1440	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	9	54	theme	human	1240:1244	arg1	basophils					1246:1254	human basophils	1240:1254	human basophils	1240:1254	Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils.
28474843	2	55	theme	asthma	317:322	arg1	induction					265:273	the induction	261:273	the induction of cockroach allergen-induced allergy and asthma	261:322	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	2	56	from	components	198:207	arg1	allergen					222:229	cockroach allergen	212:229	cockroach allergen	212:229	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	4	57	theme	METHODS	448:454	arg1	glycans					465:471	METHODS N-linked glycans	448:471	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2	448:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	5	58	theme	binding	681:687	arg1	immunoassays					689:700	solid-phase binding immunoassays	669:700	solid-phase binding immunoassays	669:700	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	2	59	theme	allergy	305:311	arg1	induction					265:273	the induction	261:273	the induction of cockroach allergen-induced allergy and asthma	261:322	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	14	60	theme	allergen-induced	1853:1868	arg1	reactions					1877:1885	allergen-induced immune reactions	1853:1885	allergen-induced immune reactions	1853:1885	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	12	61	theme	human	1645:1649	arg1	basophils					1651:1659	human basophils	1645:1659	human basophils	1645:1659	Neutralizing antibody to DCIR, but not DC-SIGN, significantly inhibited Bla g 2 uptake by human basophils.
28474843	14	62	from	glycan	1944:1949	arg1	function					1963:1970	basophil function	1954:1970	basophil function	1954:1970	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	4	63	theme	cockroach	497:505	arg1	g					520:520	naturally purified cockroach allergen Bla g 2	478:522	naturally purified cockroach allergen Bla g 2	478:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	12	64	theme	g	1631:1631	arg1	uptake					1635:1640	Bla g 2 uptake	1627:1640	Bla g 2 uptake by human basophils	1627:1659	Neutralizing antibody to DCIR, but not DC-SIGN, significantly inhibited Bla g 2 uptake by human basophils.
28474843	4	65	theme	Bla	516:518	arg1	g					520:520	naturally purified cockroach allergen Bla g 2	478:522	naturally purified cockroach allergen Bla g 2	478:522	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	4	66	theme	mass	556:559	arg1	spectrometry					561:572	MALDI-TOF mass spectrometry	546:572	MALDI-TOF mass spectrometry	546:572	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	14	67	dep	CONCLUSIONS	1737:1747	arg1	indicate					1768:1775	indicate	1768:1775	indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR	1768:1895	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	11	68	theme	human	1538:1542	arg1	basophils					1544:1552	human basophils	1538:1552	human basophils	1538:1552	An analysis of CLRs revealed the expression of DC-SIGN and DCIR, but not MRC1 and dectin-1, in human basophils.
28474843	2	69	theme	cockroach	278:286	arg1	allergy					305:311	cockroach allergen-induced allergy	278:311	cockroach allergen-induced allergy	278:311	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	6	70	theme	cockroach	711:719	arg1	glycan					732:737	cockroach associated glycan	711:737	cockroach associated glycan	711:737	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	4	71	theme	MALDI-TOF	546:554	arg1	spectrometry					561:572	MALDI-TOF mass spectrometry	546:572	MALDI-TOF mass spectrometry	546:572	METHODS N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry.
28474843	10	72	theme	histamine	1324:1332	arg1	release					1334:1340	histamine release	1324:1340	histamine release	1324:1340	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	8	73	theme	N-acetyl	1100:1107	arg1	glucosamine					1109:1119	N-acetyl glucosamine	1100:1119	N-acetyl glucosamine (GlcNAc)	1100:1128	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	8	73	theme	N-acetyl	1100:1107	arg1	GlcNAc					1122:1127	GlcNAc	1122:1127	GlcNAc	1122:1127	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	5	74	theme	cockroach	586:594	arg1	allergen					596:603	cockroach allergen	586:603	cockroach allergen	586:603	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	3	75	theme	cockroach-associated	381:400	arg1	glycan					402:407	cockroach-associated glycan	381:407	cockroach-associated glycan	381:407	We sought to examine the role of cockroach-associated glycan in regulating human basophil function.
28474843	6	76	theme	human	785:789	arg1	basophils					791:799	human basophils	785:799	human basophils	785:799	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	14	77	from	role	1803:1806	arg1	reactions					1877:1885	allergen-induced immune reactions	1853:1885	allergen-induced immune reactions	1853:1885	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	9	78	theme	Bla	1146:1148	arg1	g					1150:1150	Deglycosylated Bla g 2	1131:1152	Deglycosylated Bla g 2	1131:1152	Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils.
28474843	5	79	theme	solid-phase	669:679	arg1	immunoassays					689:700	solid-phase binding immunoassays	669:700	solid-phase binding immunoassays	669:700	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	1	80	theme	Cockroach	79:87	arg1	exposure					98:105	INTRODUCTION Cockroach allergen exposure	66:105	INTRODUCTION Cockroach allergen exposure	66:105	INTRODUCTION Cockroach allergen exposure elicits cockroach sensitization and poses an increased risk for asthma.
28474843	14	81	theme	allergen-associated	1822:1840	arg1	glycans					1842:1848	cockroach allergen-associated glycans	1812:1848	cockroach allergen-associated glycans	1812:1848	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	9	82	gly	Deglycosylated	1131:1144	arg1	g					1150:1150	Deglycosylated Bla g 2	1131:1152	Deglycosylated Bla g 2	1131:1152	Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils.
28474843	5	83	theme	cockroach	623:631	arg1	subjects					642:649	cockroach allergic subjects	623:649	cockroach allergic subjects	623:649	Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays.
28474843	2	84	from	mechanisms	239:248	arg1	allergen					222:229	cockroach allergen	212:229	cockroach allergen	212:229	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	3	85	theme	human	423:427	arg1	function					438:445	human basophil function	423:445	human basophil function	423:445	We sought to examine the role of cockroach-associated glycan in regulating human basophil function.
28474843	9	86	theme	reduced	1161:1167	arg1	binding					1169:1175	reduced binding	1161:1175	reduced binding to IgE	1161:1182	Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils.
28474843	1	87	theme	cockroach	115:123	arg1	sensitization					125:137	cockroach sensitization	115:137	cockroach sensitization	115:137	INTRODUCTION Cockroach allergen exposure elicits cockroach sensitization and poses an increased risk for asthma.
28474843	8	88	theme	spectrometric	965:977	arg1	analysis					979:986	MALDI-TOF mass spectrometric analysis	950:986	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2	942:1011	RESULTS MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc).
28474843	10	89	from	subjects	1433:1440	arg1	serum					1403:1407	serum	1403:1407	serum from cockroach allergic subjects	1403:1440	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	13	90	theme	allergen	1701:1708	arg1	bindings					1679:1686	A dose-dependent bindings	1662:1686	A dose-dependent bindings of cockroach allergen to DCIR	1662:1716	A dose-dependent bindings of cockroach allergen to DCIR was also observed.
28474843	2	91	theme	major	192:196	arg1	components					198:207	the major components	188:207	the major components in cockroach allergen	188:229	However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive.
28474843	6	92	theme	histamine	742:750	arg1	release					752:758	histamine release	742:758	histamine release	742:758	Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined.
28474843	0	93	theme	human	41:45	arg1	function					56:63	human basophil function	41:63	human basophil function	41:63	N-glycan in cockroach allergen regulates human basophil function.
28474843	10	94	theme	cockroach	1414:1422	arg1	subjects					1433:1440	cockroach allergic subjects	1414:1440	cockroach allergic subjects	1414:1440	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	14	95	theme	immune	1870:1875	arg1	reactions					1877:1885	allergen-induced immune reactions	1853:1885	allergen-induced immune reactions	1853:1885	CONCLUSIONS These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.
28474843	13	96	theme	dose-dependent	1664:1677	arg1	bindings					1679:1686	A dose-dependent bindings	1662:1686	A dose-dependent bindings of cockroach allergen to DCIR	1662:1716	A dose-dependent bindings of cockroach allergen to DCIR was also observed.
28474843	10	97	attach	derived	1279:1285	arg2	N-glycan					1270:1277	N-glycan	1270:1277	N-glycan derived from Bla g 2	1270:1298	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	10	97	attach	derived	1279:1285	arg1	g					1296:1296	Bla g 2	1292:1298	Bla g 2	1292:1298	In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects.
28474843	7	98	theme	lectin	836:841	arg1	CLRs					854:857	CLRs	854:857	CLRs	854:857	Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated.
28474843	7	98	theme	lectin	836:841	arg1	receptors					843:851	C-type lectin receptors	829:851	C-type lectin receptors (CLRs)	829:858	Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated.
28474843	9	99	theme	histamine	1217:1225	arg1	release					1227:1233	histamine release	1217:1233	histamine release from human basophils	1217:1254	Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils.
29283203	0	0	theme	Conjugate	92:100	arg1	Structure					11:19	Structure	11:19	Structure	11:19	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	0	0	theme	Conjugate	92:100	arg1	Cytotoxicity					26:37	Cytotoxicity	26:37	Cytotoxicity	26:37	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	0	0	theme	Conjugate	92:100	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis	0:8	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	2	1	link	N-linked	333:340	arg1	tetrazole-saccharinates					342:364	some N-linked tetrazole-saccharinates	328:364	some N-linked tetrazole-saccharinates	328:364	We disclosed recently that some N-linked tetrazole-saccharinates bind selectively to copper, forming complexes that are highly cytotoxic towards cancer cells.
29283203	4	2	theme	1,1-dioxide	797:807	arg1	structure					643:651	structure	643:651	structure	643:651	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	4	2	theme	1,1-dioxide	797:807	arg1	synthesis					632:640	synthesis	632:640	synthesis	632:640	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	4	2	theme	1,1-dioxide	797:807	arg1	photochemistry					668:681	monomeric photochemistry	658:681	monomeric photochemistry	658:681	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	0	3	theme	Thiadiazolyl-Saccharinate	66:90	arg1	Conjugate					92:100	a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate	42:100	a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate	42:100	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	1	4	theme	copper	164:169	arg1	concentration					171:183	the copper concentration	160:183	the copper concentration	160:183	Reports showing that the copper concentration is considerably higher in neoplasms than in normal tissues prompted the need to develop selective copper chelators.
29283203	1	4	theme	copper	164:169	arg1	higher					201:206	higher	201:206	higher	201:206	Reports showing that the copper concentration is considerably higher in neoplasms than in normal tissues prompted the need to develop selective copper chelators.
29283203	9	5	theme	copper	1629:1634	arg1	toxicity					1660:1667	a copper concentration-dependent toxicity	1627:1667	a copper concentration-dependent toxicity	1627:1667	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	11	6	theme	cancer	1890:1895	arg1	chemotherapy					1897:1908	cancer chemotherapy	1890:1908	cancer chemotherapy based on chelating agents	1890:1934	Thus, MTSB represents a promising lead for cancer chemotherapy based on chelating agents.
29283203	10	7	from	effective	1752:1760	arg1	particular					1726:1735	particular	1726:1735	particular	1726:1735	In particular, MTSB was most effective towards the hepatic (HepG2), neuroblastoma (SH-SY5), and lymphoma cell lines (U937).
29283203	9	8	dep	in	1587:1588	arg1	vitro					1590:1594	vitro	1590:1594	vitro	1590:1594	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	8	9	theme	5-methyl-1,3,4-thiadiazole	1470:1495	arg1	block					1506:1510	the 5-methyl-1,3,4-thiadiazole building block	1466:1510	the 5-methyl-1,3,4-thiadiazole building block	1466:1510	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	6	10	theme	X-ray	1105:1109	arg1	crystallography					1111:1125	X-ray crystallography	1105:1125	X-ray crystallography	1105:1125	The crystal structure was investigated by combining X-ray crystallography with infrared and Raman spectroscopies.
29283203	5	11	theme	monomeric	821:829	arg1	structure					831:839	The monomeric structure	817:839	The monomeric structure	817:839	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	9	12	theme	MTSB	1615:1618	arg1	assays					1605:1610	in vitro toxicity assays	1587:1610	in vitro toxicity assays of MTSB	1587:1618	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	9	13	theme	normal	1709:1714	arg1	cells					1716:1720	normal cells	1709:1720	normal cells	1709:1720	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	1	14	theme	selective	273:281	arg1	chelators					290:298	selective copper chelators	273:298	selective copper chelators	273:298	Reports showing that the copper concentration is considerably higher in neoplasms than in normal tissues prompted the need to develop selective copper chelators.
29283203	7	15	with	similar	1219:1225	arg1	interaction					1271:1281	an S⋅⋅⋅N interaction	1262:1281	an S⋅⋅⋅N interaction	1262:1281	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	8	16	theme	MTSB	1410:1413	arg1	photostability					1392:1405	a high photostability	1385:1405	a high photostability of MTSB	1385:1413	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	5	17	theme	chemical	959:966	arg1	calculations					968:979	quantum chemical calculations	951:979	quantum chemical calculations	951:979	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	8	18	theme	building	1497:1504	arg1	block					1506:1510	the 5-methyl-1,3,4-thiadiazole building block	1466:1510	the 5-methyl-1,3,4-thiadiazole building block	1466:1510	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	5	19	theme	charge	842:847	arg1	analysis					857:864	charge density analysis	842:864	charge density analysis	842:864	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	9	20	theme	toxicity	1596:1603	arg1	assays					1605:1610	in vitro toxicity assays	1587:1610	in vitro toxicity assays of MTSB	1587:1618	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	5	21	theme	MTSB	907:910	arg1	structure					831:839	The monomeric structure	817:839	The monomeric structure	817:839	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	5	21	theme	MTSB	907:910	arg1	spectrum					895:902	characteristic infrared spectrum	871:902	characteristic infrared spectrum	871:902	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	5	21	theme	MTSB	907:910	arg1	analysis					857:864	charge density analysis	842:864	charge density analysis	842:864	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	1	22	theme	copper	283:288	arg1	chelators					290:298	selective copper chelators	273:298	selective copper chelators	273:298	Reports showing that the copper concentration is considerably higher in neoplasms than in normal tissues prompted the need to develop selective copper chelators.
29283203	8	23	theme	Matrix	1357:1362	arg1	irradiation					1364:1374	Matrix irradiation	1357:1374	Matrix irradiation	1357:1374	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	10	24	theme	lymphoma	1819:1826	arg1	lines					1833:1837	lymphoma cell lines	1819:1837	lymphoma cell lines (U937)	1819:1844	In particular, MTSB was most effective towards the hepatic (HepG2), neuroblastoma (SH-SY5), and lymphoma cell lines (U937).
29283203	10	24	theme	lymphoma	1819:1826	arg1	U937					1840:1843	U937	1840:1843	U937	1840:1843	In particular, MTSB was most effective towards the hepatic (HepG2), neuroblastoma (SH-SY5), and lymphoma cell lines (U937).
29283203	11	25	theme	chelating	1919:1927	arg1	agents					1929:1934	chelating agents	1919:1934	chelating agents	1919:1934	Thus, MTSB represents a promising lead for cancer chemotherapy based on chelating agents.
29283203	0	26	theme	Interaction	126:136	arg1	Relevance					107:115	The Relevance	103:115	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.	0:137	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	9	27	theme	in	1587:1588	arg1	assays					1605:1610	in vitro toxicity assays	1587:1610	in vitro toxicity assays of MTSB	1587:1618	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	8	28	theme	photostabilizing	1529:1544	arg1	effect					1546:1551	the photostabilizing effect	1525:1551	the photostabilizing effect of the saccharyl system	1525:1575	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	4	29	theme	sulphanyl-bridged	688:704	arg1	MTSB					810:813	MTSB	810:813	MTSB	810:813	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	4	29	theme	sulphanyl-bridged	688:704	arg1	1,1-dioxide					797:807	a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide	686:807	a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB)	686:814	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	0	30	theme	S⋅⋅⋅N	120:124	arg1	Interaction					126:136	S⋅⋅⋅N Interaction	120:136	S⋅⋅⋅N Interaction	120:136	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	11	31	theme	promising	1871:1879	arg1	lead					1881:1884	a promising lead	1869:1884	a promising lead for cancer chemotherapy based on chelating agents	1869:1934	Thus, MTSB represents a promising lead for cancer chemotherapy based on chelating agents.
29283203	2	32	theme	cancer	446:451	arg1	cells					453:457	cancer cells	446:457	cancer cells	446:457	We disclosed recently that some N-linked tetrazole-saccharinates bind selectively to copper, forming complexes that are highly cytotoxic towards cancer cells.
29283203	7	33	theme	S⋅⋅⋅N	1265:1269	arg1	interaction					1271:1281	an S⋅⋅⋅N interaction	1262:1281	an S⋅⋅⋅N interaction	1262:1281	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	5	34	theme	infrared	1030:1037	arg1	spectroscopy					1039:1050	matrix-isolation infrared spectroscopy	1013:1050	matrix-isolation infrared spectroscopy	1013:1050	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	9	35	theme	concentration-dependent	1636:1658	arg1	toxicity					1660:1667	a copper concentration-dependent toxicity	1627:1667	a copper concentration-dependent toxicity	1627:1667	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	5	36	theme	characteristic	871:884	arg1	spectrum					895:902	characteristic infrared spectrum	871:902	characteristic infrared spectrum	871:902	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	7	37	theme	isolated	1202:1209	arg1	MTSB					1211:1214	isolated MTSB	1202:1214	isolated MTSB	1202:1214	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	8	38	theme	parent	1428:1433	arg1	tetrazole-saccharinates					1435:1457	parent tetrazole-saccharinates	1428:1457	parent tetrazole-saccharinates	1428:1457	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	4	39	dep	thiadiazolyl-saccharinate	706:730	arg1	-1,2-benzothiazole					778:795	-1,2-benzothiazole	778:795	-1,2-benzothiazole	778:795	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	5	40	theme	quantum	951:957	arg1	calculations					968:979	quantum chemical calculations	951:979	quantum chemical calculations	951:979	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	5	41	theme	infrared	886:893	arg1	spectrum					895:902	characteristic infrared spectrum	871:902	characteristic infrared spectrum	871:902	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	4	42	dep	synthesis	632:640	arg1	the					628:630	the	628:630	the	628:630	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	8	43	theme	saccharyl	1560:1568	arg1	system					1570:1575	the saccharyl system	1556:1575	the saccharyl system	1556:1575	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	5	44	theme	matrix-isolation	1013:1028	arg1	spectroscopy					1039:1050	matrix-isolation infrared spectroscopy	1013:1050	matrix-isolation infrared spectroscopy	1013:1050	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	6	45	theme	crystal	1057:1063	arg1	structure					1065:1073	The crystal structure	1053:1073	The crystal structure	1053:1073	The crystal structure was investigated by combining X-ray crystallography with infrared and Raman spectroscopies.
29283203	7	46	theme	MTSB	1211:1214	arg1	similar					1219:1225	similar	1219:1225	similar	1219:1225	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	7	46	theme	MTSB	1211:1214	arg1	structure					1189:1197	the structure	1185:1197	the structure of isolated MTSB	1185:1214	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	10	47	from	particular	1726:1735	arg1	effective					1752:1760	effective	1752:1760	effective	1752:1760	In particular, MTSB was most effective towards the hepatic (HepG2), neuroblastoma (SH-SY5), and lymphoma cell lines (U937).
29283203	7	48	theme	molecule	1328:1335	arg1	structure					1311:1319	the structure	1307:1319	the structure of the molecule and of the crystal	1307:1354	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	3	49	theme	tetrazoles	539:548	arg1	photoreactivity					520:534	the photoreactivity	516:534	the photoreactivity of tetrazoles	516:548	Because tetrazole-saccharinates are photolabile, due to the photoreactivity of tetrazoles, we proposed thiadiazolyl-saccharinates as an alternative.
29283203	7	50	located	found	1235:1239	arg1	crystal					1248:1254	the crystal	1244:1254	the crystal	1244:1254	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	7	50	located	found	1235:1239	arg2	that					1230:1233	that	1230:1233	that	1230:1233	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	5	51	theme	density	849:855	arg1	analysis					857:864	charge density analysis	842:864	charge density analysis	842:864	The monomeric structure, charge density analysis, and characteristic infrared spectrum of MTSB were investigated theoretically, using quantum chemical calculations, and also experimentally, using matrix-isolation infrared spectroscopy.
29283203	10	52	theme	cell	1828:1831	arg1	lines					1833:1837	lymphoma cell lines	1819:1837	lymphoma cell lines (U937)	1819:1844	In particular, MTSB was most effective towards the hepatic (HepG2), neuroblastoma (SH-SY5), and lymphoma cell lines (U937).
29283203	10	52	theme	cell	1828:1831	arg1	U937					1840:1843	U937	1840:1843	U937	1840:1843	In particular, MTSB was most effective towards the hepatic (HepG2), neuroblastoma (SH-SY5), and lymphoma cell lines (U937).
29283203	1	53	theme	normal	229:234	arg1	tissues					236:242	normal tissues	229:242	normal tissues	229:242	Reports showing that the copper concentration is considerably higher in neoplasms than in normal tissues prompted the need to develop selective copper chelators.
29283203	8	54	theme	system	1570:1575	arg1	effect					1546:1551	the photostabilizing effect	1525:1551	the photostabilizing effect of the saccharyl system	1525:1575	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	2	55	theme	N-linked	333:340	arg1	tetrazole-saccharinates					342:364	some N-linked tetrazole-saccharinates	328:364	some N-linked tetrazole-saccharinates	328:364	We disclosed recently that some N-linked tetrazole-saccharinates bind selectively to copper, forming complexes that are highly cytotoxic towards cancer cells.
29283203	0	56	theme	Sulphanyl-Bridged	48:64	arg1	Conjugate					92:100	a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate	42:100	a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate	42:100	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	4	57	theme	thiadiazolyl-saccharinate	706:730	arg1	MTSB					810:813	MTSB	810:813	MTSB	810:813	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	4	57	theme	thiadiazolyl-saccharinate	706:730	arg1	1,1-dioxide					797:807	a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide	686:807	a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB)	686:814	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	8	58	theme	high	1387:1390	arg1	photostability					1392:1405	a high photostability	1385:1405	a high photostability of MTSB	1385:1413	Matrix irradiation revealed a high photostability of MTSB, compared to parent tetrazole-saccharinates and to the 5-methyl-1,3,4-thiadiazole building block, emphasizing the photostabilizing effect of the saccharyl system.
29283203	9	59	theme	cancer	1677:1682	arg1	cells					1684:1688	cancer cells	1677:1688	cancer cells	1677:1688	Finally, in vitro toxicity assays of MTSB showed a copper concentration-dependent toxicity against cancer cells, without affecting normal cells.
29283203	7	60	theme	crystal	1348:1354	arg1	structure					1311:1319	the structure	1307:1319	the structure of the molecule and of the crystal	1307:1354	Results show that the structure of isolated MTSB is similar to that found in the crystal, with an S⋅⋅⋅N interaction clearly contributing to the structure of the molecule and of the crystal.
29283203	0	61	theme	New	44:46	arg1	Conjugate					92:100	a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate	42:100	a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate	42:100	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	0	62	dep	Synthesis	0:8	arg1	Relevance					107:115	The Relevance	103:115	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.	0:137	Synthesis, Structure, and Cytotoxicity of a New Sulphanyl-Bridged Thiadiazolyl-Saccharinate Conjugate: The Relevance of S⋅⋅⋅N Interaction.
29283203	4	63	theme	monomeric	658:666	arg1	photochemistry					668:681	monomeric photochemistry	658:681	monomeric photochemistry	658:681	Herein we describe the synthesis, structure, and monomeric photochemistry of a sulphanyl-bridged thiadiazolyl-saccharinate, 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulphanyl]-1,2-benzothiazole 1,1-dioxide (MTSB).
29283203	6	64	theme	Raman	1145:1149	arg1	spectroscopies					1151:1164	Raman spectroscopies	1145:1164	Raman spectroscopies	1145:1164	The crystal structure was investigated by combining X-ray crystallography with infrared and Raman spectroscopies.
28229220	11	0	theme	nuclear	1601:1607	arg1	translocation					1609:1621	nuclear translocation	1601:1621	nuclear translocation of FoxO3	1601:1630	Moreover, we observed that HepaCAM induced nuclear translocation of FoxO3.
28229220	9	1	theme	inhibitory	1332:1341	arg1	effects					1343:1349	the inhibitory effects	1328:1349	the inhibitory effects on cell proliferation, viability and protein expression	1328:1405	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	9	2	with	treatment	1239:1247	arg1	LY294002					1310:1317	the PI3K inhibitor LY294002	1291:1317	the PI3K inhibitor LY294002	1291:1317	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	9	3	theme	inhibitor	1300:1308	arg1	LY294002					1310:1317	the PI3K inhibitor LY294002	1291:1317	the PI3K inhibitor LY294002	1291:1317	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	12	4	theme	bladder	1760:1766	arg1	cancer					1768:1773	bladder cancer	1760:1773	bladder cancer	1760:1773	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	1	5	theme	tumor	238:242	arg1	HepaCAM					121:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	5	theme	tumor	238:242	arg1	gene					255:258	a tumor suppressor gene	236:258	a tumor suppressor gene that mediates diverse cellular bio-functions	236:303	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	8	6	theme	reduced	1167:1173	arg1	p-AKT					1175:1179	reduced p-AKT and p-FoxO protein expression	1167:1209	p-AKT	1175:1179	Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression.
28229220	4	7	dep	METHODS	525:531	arg1	HepaCAM					533:539	HepaCAM	533:539	HepaCAM	533:539	METHODS HepaCAM and FoxO3 expression were detected by immunohistochemistry staining.
28229220	4	7	dep	METHODS	525:531	arg1	expression					551:560	FoxO3 expression	545:560	FoxO3 expression	545:560	METHODS HepaCAM and FoxO3 expression were detected by immunohistochemistry staining.
28229220	4	7	dep	METHODS	525:531	arg1	METHODS					525:531	METHODS HepaCAM and FoxO3 expression	525:560	METHODS HepaCAM and FoxO3 expression	525:560	METHODS HepaCAM and FoxO3 expression were detected by immunohistochemistry staining.
28229220	10	8	theme	AKT	1538:1540	arg1	SC79					1552:1555	the AKT activator SC79	1534:1555	the AKT activator SC79	1534:1555	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	2	9	theme	transcription	346:358	arg1	factors					360:366	the FoxO transcription factors	337:366	the FoxO transcription factors	337:366	Recent studies have shown that the FoxO transcription factors play a pivotal role during cancer progression.
28229220	1	10	theme	suppressor	244:253	arg1	HepaCAM					121:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	10	theme	suppressor	244:253	arg1	gene					255:258	a tumor suppressor gene	236:258	a tumor suppressor gene that mediates diverse cellular bio-functions	236:303	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	8	11	theme	p-FoxO	1185:1190	arg1	expression					1200:1209	reduced p-AKT and p-FoxO protein expression	1167:1209	expression	1200:1209	Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression.
28229220	5	12	from	effect	626:631	arg1	viability					669:677	viability	669:677	viability	669:677	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	5	12	from	effect	626:631	arg1	proliferation					651:663	proliferation	651:663	proliferation	651:663	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	10	13	theme	SC79	1552:1555	arg1	viability					1498:1506	viability	1498:1506	viability	1498:1506	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	10	13	theme	SC79	1552:1555	arg1	expression					1520:1529	protein expression	1512:1529	protein expression	1512:1529	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	10	13	theme	SC79	1552:1555	arg1	proliferation					1483:1495	cell proliferation	1478:1495	cell proliferation	1478:1495	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	6	14	theme	FoxO3	817:821	arg1	translocation					800:812	the nuclear translocation	788:812	the nuclear translocation of FoxO3	788:821	We observed the nuclear translocation of FoxO3 by immunofluorescence staining after expressing HepaCAM.
28229220	0	15	theme	AKT/FoxO	95:102	arg1	pathway					104:110	the AKT/FoxO pathway	91:110	the AKT/FoxO pathway	91:110	Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway.
28229220	9	16	theme	cell	1354:1357	arg1	proliferation					1359:1371	cell proliferation	1354:1371	cell proliferation	1354:1371	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	5	17	theme	MTT	744:746	arg1	assay					748:752	the MTT assay	740:752	the MTT assay	740:752	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	5	17	theme	MTT	744:746	arg1	formation					729:737	colony formation	722:737	colony formation	722:737	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	8	18	theme	HepaCAM	1086:1092	arg1	re-expression					1069:1081	re-expression	1069:1081	re-expression of HepaCAM	1069:1092	Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression.
28229220	11	19	theme	FoxO3	1626:1630	arg1	translocation					1609:1621	nuclear translocation	1601:1621	nuclear translocation of FoxO3	1601:1630	Moreover, we observed that HepaCAM induced nuclear translocation of FoxO3.
28229220	10	20	theme	protein	1512:1518	arg1	expression					1520:1529	protein expression	1512:1529	protein expression	1512:1529	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	7	21	theme	HepaCAM	888:894	arg1	depletion					896:904	HepaCAM depletion	888:904	HepaCAM depletion	888:904	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	2	22	theme	cancer	395:400	arg1	progression					402:412	cancer progression	395:412	cancer progression	395:412	Recent studies have shown that the FoxO transcription factors play a pivotal role during cancer progression.
28229220	8	23	theme	protein	1192:1198	arg1	expression					1200:1209	reduced p-AKT and p-FoxO protein expression	1167:1209	expression	1200:1209	Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression.
28229220	4	24	theme	immunohistochemistry	579:598	arg1	staining					600:607	immunohistochemistry staining	579:607	immunohistochemistry staining	579:607	METHODS HepaCAM and FoxO3 expression were detected by immunohistochemistry staining.
28229220	6	25	theme	nuclear	792:798	arg1	translocation					800:812	the nuclear translocation	788:812	the nuclear translocation of FoxO3	788:821	We observed the nuclear translocation of FoxO3 by immunofluorescence staining after expressing HepaCAM.
28229220	9	26	theme	combined	1230:1237	arg1	treatment					1239:1247	the combined treatment	1226:1247	the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002	1226:1317	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	1	27	link	N-linked	133:140	arg1	member					170:175	a member	168:175	a member of the immunoglobulin superfamily	168:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	27	link	N-linked	133:140	arg1	HepaCAM					121:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	27	link	N-linked	133:140	arg1	glycoprotein					142:153	an N-linked glycoprotein	130:153	an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily	130:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	8	28	theme	cell	1133:1136	arg1	formation					1145:1153	BIU-87 cell colony formation	1126:1153	BIU-87 cell colony formation	1126:1153	Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression.
28229220	8	29	theme	colony	1138:1143	arg1	formation					1145:1153	BIU-87 cell colony formation	1126:1153	BIU-87 cell colony formation	1126:1153	Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression.
28229220	12	30	dep	CONCLUSIONS	1633:1643	arg1	implicated					1658:1667	implicated	1658:1667	implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway	1658:1798	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	10	31	theme	cell	1478:1481	arg1	proliferation					1483:1495	cell proliferation	1478:1495	cell proliferation	1478:1495	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	10	32	theme	activator	1542:1550	arg1	SC79					1552:1555	the AKT activator SC79	1534:1555	the AKT activator SC79	1534:1555	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	12	33	theme	therapeutic	1706:1716	arg1	target					1718:1723	a novel therapeutic target	1698:1723	a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway	1698:1798	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	12	33	theme	therapeutic	1706:1716	arg1	HepaCAM					1674:1680	HepaCAM	1674:1680	HepaCAM	1674:1680	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	2	34	theme	pivotal	375:381	arg1	role					383:386	a pivotal role	373:386	a pivotal role	373:386	Recent studies have shown that the FoxO transcription factors play a pivotal role during cancer progression.
28229220	1	35	theme	diverse	274:280	arg1	bio-functions					291:303	diverse cellular bio-functions	274:303	diverse cellular bio-functions	274:303	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	7	36	theme	adjacent	961:968	arg1	tissues					977:983	adjacent normal tissues	961:983	adjacent normal tissues	961:983	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	2	37	theme	Recent	306:311	arg1	studies					313:319	Recent studies	306:319	Recent studies	306:319	Recent studies have shown that the FoxO transcription factors play a pivotal role during cancer progression.
28229220	12	38	theme	novel	1700:1704	arg1	target					1718:1723	a novel therapeutic target	1698:1723	a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway	1698:1798	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	12	38	theme	novel	1700:1704	arg1	HepaCAM					1674:1680	HepaCAM	1674:1680	HepaCAM	1674:1680	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	1	39	theme	superfamily	199:209	arg1	member					170:175	a member	168:175	a member of the immunoglobulin superfamily	168:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	39	theme	superfamily	199:209	arg1	glycoprotein					142:153	an N-linked glycoprotein	130:153	an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily	130:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	0	40	theme	HepaCAM	18:24	arg1	Overexpression					0:13	Overexpression	0:13	Overexpression of HepaCAM	0:24	Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway.
28229220	1	41	theme	cellular	282:289	arg1	bio-functions					291:303	diverse cellular bio-functions	274:303	diverse cellular bio-functions	274:303	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	9	42	theme	HepaCAM-overexpressing	1252:1273	arg1	adenovirus					1275:1284	HepaCAM-overexpressing adenovirus	1252:1284	HepaCAM-overexpressing adenovirus	1252:1284	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	1	43	theme	PURPOSE	113:119	arg1	HepaCAM					121:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	43	theme	PURPOSE	113:119	arg1	gene					255:258	a tumor suppressor gene	236:258	a tumor suppressor gene that mediates diverse cellular bio-functions	236:303	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	43	theme	PURPOSE	113:119	arg1	glycoprotein					142:153	an N-linked glycoprotein	130:153	an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily	130:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	9	44	from	effects	1343:1349	arg1	expression					1396:1405	protein expression	1388:1405	protein expression	1388:1405	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	9	44	from	effects	1343:1349	arg1	proliferation					1359:1371	cell proliferation	1354:1371	cell proliferation	1354:1371	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	9	44	from	effects	1343:1349	arg1	viability					1374:1382	viability	1374:1382	viability	1374:1382	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	0	45	theme	cancer	43:48	arg1	proliferation					55:67	bladder cancer cell proliferation	35:67	bladder cancer cell proliferation	35:67	Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway.
28229220	5	46	theme	colony	722:727	arg1	assay					748:752	the MTT assay	740:752	the MTT assay	740:752	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	5	46	theme	colony	722:727	arg1	blotting					766:773	Western blotting	758:773	Western blotting	758:773	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	5	46	theme	colony	722:727	arg1	formation					729:737	colony formation	722:737	colony formation	722:737	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	9	47	theme	adenovirus	1275:1284	arg1	treatment					1239:1247	the combined treatment	1226:1247	the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002	1226:1317	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	12	48	theme	cancer	1768:1773	arg1	proliferation					1743:1755	the proliferation	1739:1755	the proliferation of bladder cancer	1739:1773	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	1	49	theme	immunoglobulin	184:197	arg1	superfamily					199:209	the immunoglobulin superfamily	180:209	the immunoglobulin superfamily	180:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	0	50	theme	bladder	35:41	arg1	proliferation					55:67	bladder cancer cell proliferation	35:67	bladder cancer cell proliferation	35:67	Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway.
28229220	8	51	theme	BIU-87	1126:1131	arg1	formation					1145:1153	BIU-87 cell colony formation	1126:1153	BIU-87 cell colony formation	1126:1153	Furthermore, re-expression of HepaCAM significantly disrupted T24 and BIU-87 cell colony formation, as well as reduced p-AKT and p-FoxO protein expression.
28229220	9	52	theme	protein	1388:1394	arg1	expression					1396:1405	protein expression	1388:1405	protein expression	1388:1405	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	5	53	theme	bladder	682:688	arg1	cancer					690:695	bladder cancer	682:695	bladder cancer	682:695	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	4	54	theme	FoxO3	545:549	arg1	expression					551:560	FoxO3 expression	545:560	FoxO3 expression	545:560	METHODS HepaCAM and FoxO3 expression were detected by immunohistochemistry staining.
28229220	4	54	theme	FoxO3	545:549	arg1	METHODS					525:531	METHODS HepaCAM and FoxO3 expression	525:560	METHODS HepaCAM and FoxO3 expression	525:560	METHODS HepaCAM and FoxO3 expression were detected by immunohistochemistry staining.
28229220	7	55	theme	FoxO3	1049:1053	arg1	degradation					1034:1044	the degradation	1030:1044	the degradation of FoxO3	1030:1053	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	2	56	theme	FoxO	341:344	arg1	factors					360:366	the FoxO transcription factors	337:366	the FoxO transcription factors	337:366	Recent studies have shown that the FoxO transcription factors play a pivotal role during cancer progression.
28229220	0	57	theme	cell	50:53	arg1	proliferation					55:67	bladder cancer cell proliferation	35:67	bladder cancer cell proliferation	35:67	Overexpression of HepaCAM inhibits bladder cancer cell proliferation and viability through the AKT/FoxO pathway.
28229220	10	58	theme	activated	1458:1466	arg1	effect					1468:1473	the activated effect	1454:1473	the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79	1454:1555	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	1	59	gly	glycoprotein	142:153	arg1	member					170:175	a member	168:175	a member of the immunoglobulin superfamily	168:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	59	gly	glycoprotein	142:153	arg1	HepaCAM					121:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	59	gly	glycoprotein	142:153	arg1	glycoprotein					142:153	an N-linked glycoprotein	130:153	an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily	130:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	9	60	theme	PI3K	1295:1298	arg1	LY294002					1310:1317	the PI3K inhibitor LY294002	1291:1317	the PI3K inhibitor LY294002	1291:1317	We found that the combined treatment of HepaCAM-overexpressing adenovirus with the PI3K inhibitor LY294002 enhanced the inhibitory effects on cell proliferation, viability and protein expression.
28229220	5	61	theme	HepaCAM	636:642	arg1	effect					626:631	the effect	622:631	the effect of HepaCAM on the proliferation and viability of bladder cancer	622:695	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	7	62	dep	RESULTS	880:886	arg1	discovered					910:919	discovered	910:919	was discovered in bladder cancer tissues compared with adjacent normal tissues	906:983	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	7	62	dep	RESULTS	880:886	arg1	associated					1014:1023	associated	1014:1023	was associated with the degradation of FoxO3	1010:1053	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	7	63	theme	normal	970:975	arg1	tissues					977:983	adjacent normal tissues	961:983	adjacent normal tissues	961:983	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	7	64	theme	decreased	994:1002	arg1	level					1004:1008	the decreased level	990:1008	the decreased level	990:1008	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	3	65	theme	FoxO	473:476	arg1	family					478:483	the FoxO family	469:483	the FoxO family	469:483	Here, we explored the correlation between HepaCAM and the FoxO family via regulation of the PI3K/AKT pathway.
28229220	12	66	theme	AKT/FoxO	1783:1790	arg1	pathway					1792:1798	the AKT/FoxO pathway	1779:1798	the AKT/FoxO pathway	1779:1798	CONCLUSIONS Our research implicated that HepaCAM may function as a novel therapeutic target that inhibits the proliferation of bladder cancer via the AKT/FoxO pathway.
28229220	5	67	theme	AKT	705:707	arg1	signaling					709:717	AKT signaling	705:717	AKT signaling	705:717	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	1	68	theme	N-linked	133:140	arg1	member					170:175	a member	168:175	a member of the immunoglobulin superfamily	168:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	68	theme	N-linked	133:140	arg1	HepaCAM					121:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM	113:127	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	1	68	theme	N-linked	133:140	arg1	glycoprotein					142:153	an N-linked glycoprotein	130:153	an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily	130:209	PURPOSE HepaCAM, an N-linked glycoprotein that encodes a member of the immunoglobulin superfamily, has been reported to be a tumor suppressor gene that mediates diverse cellular bio-functions.
28229220	7	69	theme	bladder	924:930	arg1	tissues					939:945	bladder cancer tissues	924:945	bladder cancer tissues compared with adjacent normal tissues	924:983	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	10	70	from	effect	1468:1473	arg1	viability					1498:1506	viability	1498:1506	viability	1498:1506	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	10	70	from	effect	1468:1473	arg1	expression					1520:1529	protein expression	1512:1529	protein expression	1512:1529	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	10	70	from	effect	1468:1473	arg1	proliferation					1483:1495	cell proliferation	1478:1495	cell proliferation	1478:1495	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	6	71	theme	immunofluorescence	826:843	arg1	staining					845:852	immunofluorescence staining	826:852	immunofluorescence staining	826:852	We observed the nuclear translocation of FoxO3 by immunofluorescence staining after expressing HepaCAM.
28229220	10	72	theme	overexpressed	1422:1434	arg1	HepaCAM					1436:1442	overexpressed HepaCAM	1422:1442	overexpressed HepaCAM	1422:1442	Additionally, overexpressed HepaCAM decreased the activated effect on cell proliferation, viability and protein expression of the AKT activator SC79.
28229220	3	73	theme	PI3K/AKT	507:514	arg1	pathway					516:522	the PI3K/AKT pathway	503:522	the PI3K/AKT pathway	503:522	Here, we explored the correlation between HepaCAM and the FoxO family via regulation of the PI3K/AKT pathway.
28229220	7	74	theme	cancer	932:937	arg1	tissues					939:945	bladder cancer tissues	924:945	bladder cancer tissues compared with adjacent normal tissues	924:983	RESULTS HepaCAM depletion was discovered in bladder cancer tissues compared with adjacent normal tissues, and the decreased level was associated with the degradation of FoxO3.
28229220	5	75	theme	Western	758:764	arg1	blotting					766:773	Western blotting	758:773	Western blotting	758:773	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	5	75	theme	Western	758:764	arg1	formation					729:737	colony formation	722:737	colony formation	722:737	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	3	76	theme	pathway	516:522	arg1	regulation					489:498	regulation	489:498	regulation of the PI3K/AKT pathway	489:522	Here, we explored the correlation between HepaCAM and the FoxO family via regulation of the PI3K/AKT pathway.
28229220	5	77	theme	cancer	690:695	arg1	viability					669:677	viability	669:677	viability	669:677	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
28229220	5	77	theme	cancer	690:695	arg1	proliferation					651:663	proliferation	651:663	proliferation	651:663	We detected the effect of HepaCAM on the proliferation and viability of bladder cancer through AKT signaling by colony formation, the MTT assay and Western blotting.
31131693	13	0	theme	novel	1933:1937	arg1	O-GlcNAcylation					1939:1953	a novel O-GlcNAcylation	1931:1953	a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function	1931:2049	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	10	1	theme	phospholamban	1604:1616	arg1	phosphorylation					1585:1599	phosphorylation	1585:1599	phosphorylation	1585:1599	OGTKO reduced phosphorylation of phospholamban and cardiac troponin I, which would negatively impact cardiac function.
31131693	13	2	theme	cardiac	2034:2040	arg1	function					2042:2049	cardiac function	2034:2049	cardiac function	2034:2049	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	3	3	theme	overload	633:640	arg1	hypertrophy					642:652	pressure overload hypertrophy	624:652	pressure overload hypertrophy	624:652	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	8	4	theme	aortic	1433:1438	arg1	constriction					1440:1451	transverse aortic constriction	1422:1451	transverse aortic constriction	1422:1451	In both groups, OGTKO with transverse aortic constriction caused significant left ventricular dysfunction.
31131693	10	5	theme	cardiac	1622:1628	arg1	troponin					1630:1637	cardiac troponin I	1622:1639	cardiac troponin I	1622:1639	OGTKO reduced phosphorylation of phospholamban and cardiac troponin I, which would negatively impact cardiac function.
31131693	4	6	dep	cardiac-specific	924:939	arg1	inducible					942:950	inducible	942:950	inducible	942:950	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	12	7	theme	compensated	1832:1842	arg1	function					1852:1859	compensated cardiac function	1832:1859	compensated cardiac function	1832:1859	Conclusions O-GlcNAcylation promotes compensated cardiac function in both early and established pathological hypertrophy.
31131693	7	8	theme	prolonged	1235:1243	arg1	O-GlcNAcylation					1245:1259	prolonged O-GlcNAcylation	1235:1259	prolonged O-GlcNAcylation	1235:1259	To assess prolonged O-GlcNAcylation during established hypertrophy, OGTKO was performed starting 18 days after surgery and mice were followed until 6 weeks post-surgery.
31131693	8	9	theme	ventricular	1477:1487	arg1	dysfunction					1489:1499	significant left ventricular dysfunction	1460:1499	significant left ventricular dysfunction	1460:1499	In both groups, OGTKO with transverse aortic constriction caused significant left ventricular dysfunction.
31131693	8	10	theme	left	1472:1475	arg1	dysfunction					1489:1499	significant left ventricular dysfunction	1460:1499	significant left ventricular dysfunction	1460:1499	In both groups, OGTKO with transverse aortic constriction caused significant left ventricular dysfunction.
31131693	13	11	theme	subunit	1985:1991	arg1	O-GlcNAcylation					1939:1953	a novel O-GlcNAcylation	1931:1953	a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function	1931:2049	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	0	12	theme	Pressure	155:162	arg1	Overload					164:171	Pressure Overload	155:171	Pressure Overload	155:171	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	3	13	theme	established	692:702	arg1	hypertrophy					717:727	established pathological hypertrophy	692:727	established pathological hypertrophy	692:727	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	4	14	theme	aortic	845:850	arg1	constriction					852:863	Transverse aortic constriction	834:863	Transverse aortic constriction	834:863	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	5	15	theme	different	1069:1077	arg1	times					1079:1083	different times	1069:1083	different times	1069:1083	O-GlcNAc transferase deficiency was induced at different times.
31131693	11	16	theme	kinase	1717:1722	arg1	O-GlcNAcylation					1690:1704	O-GlcNAcylation	1690:1704	O-GlcNAcylation of protein kinase A catalytic subunit, a kinase for phospholamban,	1690:1771	O-GlcNAcylation of protein kinase A catalytic subunit, a kinase for phospholamban, decreased with OGTKO.
31131693	0	17	theme	Kinase	71:76	arg1	A					78:78	Protein Kinase A	63:78	Protein Kinase A O-GlcNAcylation	63:94	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	1	18	theme	Background	174:183	arg1	modifications					211:223	Background Protein posttranslational modifications	174:223	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc)	174:268	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	1	19	theme	changes	341:347	arg1	effects					324:330	the functional effects	309:330	the functional effects of these changes	309:347	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	1	20	theme	posttranslational	193:209	arg1	modifications					211:223	Background Protein posttranslational modifications	174:223	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc)	174:268	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	13	21	theme	kinase	1966:1971	arg1	subunit					1985:1991	protein kinase A catalytic subunit	1958:1991	protein kinase A catalytic subunit	1958:1991	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	4	22	theme	littermate	901:910	arg1	controls					912:919	littermate controls	901:919	littermate controls	901:919	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	11	23	theme	catalytic	1726:1734	arg1	subunit					1736:1742	A catalytic subunit	1724:1742	A catalytic subunit	1724:1742	O-GlcNAcylation of protein kinase A catalytic subunit, a kinase for phospholamban, decreased with OGTKO.
31131693	0	24	theme	Early	103:107	arg1	Hypertrophy					138:148	Early and Established Pathological Hypertrophy	103:148	Early and Established Pathological Hypertrophy From Pressure Overload	103:171	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	1	25	link	O-linked	228:235	arg1	O-GlcNAc					260:267	O-GlcNAc	260:267	O-GlcNAc	260:267	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	1	25	link	O-linked	228:235	arg1	β-N-acetylglucosamine					237:257	O-linked β-N-acetylglucosamine	228:257	O-linked β-N-acetylglucosamine (O-GlcNAc)	228:268	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	11	26	dep	kinase	1717:1722	arg1	subunit					1736:1742	A catalytic subunit	1724:1742	A catalytic subunit	1724:1742	O-GlcNAcylation of protein kinase A catalytic subunit, a kinase for phospholamban, decreased with OGTKO.
31131693	0	27	theme	Established	113:123	arg1	Hypertrophy					138:148	Early and Established Pathological Hypertrophy	103:148	Early and Established Pathological Hypertrophy From Pressure Overload	103:171	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	10	28	theme	cardiac	1672:1678	arg1	function					1680:1687	cardiac function	1672:1687	cardiac function	1672:1687	OGTKO reduced phosphorylation of phospholamban and cardiac troponin I, which would negatively impact cardiac function.
31131693	0	29	theme	O-GlcNAc	0:7	arg1	Transferase					9:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	12	30	theme	early	1869:1873	arg1	hypertrophy					1904:1914	both early and established pathological hypertrophy	1864:1914	both early and established pathological hypertrophy	1864:1914	Conclusions O-GlcNAcylation promotes compensated cardiac function in both early and established pathological hypertrophy.
31131693	9	31	theme	calcium	1537:1543	arg1	SERCA2a					1562:1568	the calcium handling protein SERCA2a	1533:1568	the calcium handling protein SERCA2a	1533:1568	OGTKO did not affect levels of the calcium handling protein SERCA2a.
31131693	12	32	theme	established	1879:1889	arg1	hypertrophy					1904:1914	both early and established pathological hypertrophy	1864:1914	both early and established pathological hypertrophy	1864:1914	Conclusions O-GlcNAcylation promotes compensated cardiac function in both early and established pathological hypertrophy.
31131693	6	33	theme	2 weeks	1203:1209	arg1	post-surgery					1211:1222	2 weeks post-surgery	1203:1222	2 weeks post-surgery	1203:1222	To evaluate the initial response to pressure overload, OGTKO was completed preoperatively and mice were followed for 2 weeks post-surgery.
31131693	4	34	theme	knockout	973:980	arg1	mice					990:993	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	2	35	theme	prolonged	467:475	arg1	elevations					486:495	prolonged O-GlcNAc elevations	467:495	prolonged O-GlcNAc elevations	467:495	In other organs, O-GlcNAc promotes adaptation to acute physiological stressors; however, prolonged O-GlcNAc elevations are believed to be detrimental.
31131693	0	36	theme	Cardiac	42:48	arg1	Function					50:57	Compensated Cardiac Function	30:57	Compensated Cardiac Function	30:57	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	9	37	theme	protein	1554:1560	arg1	SERCA2a					1562:1568	the calcium handling protein SERCA2a	1533:1568	the calcium handling protein SERCA2a	1533:1568	OGTKO did not affect levels of the calcium handling protein SERCA2a.
31131693	4	38	theme	OGTKO	983:987	arg1	mice					990:993	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	3	39	theme	calcium	787:793	arg1	proteins					804:811	calcium handling proteins	787:811	calcium handling proteins	787:811	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	4	40	theme	O-GlcNAc	952:959	arg1	transferase					961:971	cardiac-specific, inducible O-GlcNAc transferase	924:971	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	2	41	theme	acute	427:431	arg1	stressors					447:455	acute physiological stressors	427:455	acute physiological stressors	427:455	In other organs, O-GlcNAc promotes adaptation to acute physiological stressors; however, prolonged O-GlcNAc elevations are believed to be detrimental.
31131693	9	42	theme	SERCA2a	1562:1568	arg1	levels					1523:1528	levels	1523:1528	levels of the calcium handling protein SERCA2a	1523:1568	OGTKO did not affect levels of the calcium handling protein SERCA2a.
31131693	3	43	theme	cardiac	580:586	arg1	function					588:595	cardiac function	580:595	cardiac function	580:595	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	4	44	theme	O-GlcNAc	1005:1012	arg1	levels					1014:1019	O-GlcNAc levels	1005:1019	O-GlcNAc levels	1005:1019	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	8	45	with	OGTKO	1411:1415	arg1	constriction					1440:1451	transverse aortic constriction	1422:1451	transverse aortic constriction	1422:1451	In both groups, OGTKO with transverse aortic constriction caused significant left ventricular dysfunction.
31131693	3	46	theme	pressure	624:631	arg1	hypertrophy					642:652	pressure overload hypertrophy	624:652	pressure overload hypertrophy	624:652	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	1	47	theme	functional	313:322	arg1	effects					324:330	the functional effects	309:330	the functional effects of these changes	309:347	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	7	48	theme	established	1268:1278	arg1	hypertrophy					1280:1290	established hypertrophy	1268:1290	established hypertrophy	1268:1290	To assess prolonged O-GlcNAcylation during established hypertrophy, OGTKO was performed starting 18 days after surgery and mice were followed until 6 weeks post-surgery.
31131693	10	49	theme	troponin	1630:1637	arg1	phosphorylation					1585:1599	phosphorylation	1585:1599	phosphorylation	1585:1599	OGTKO reduced phosphorylation of phospholamban and cardiac troponin I, which would negatively impact cardiac function.
31131693	1	50	theme	O-linked	228:235	arg1	O-GlcNAc					260:267	O-GlcNAc	260:267	O-GlcNAc	260:267	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	1	50	theme	O-linked	228:235	arg1	β-N-acetylglucosamine					237:257	O-linked β-N-acetylglucosamine	228:257	O-linked β-N-acetylglucosamine (O-GlcNAc)	228:268	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	12	51	theme	cardiac	1844:1850	arg1	function					1852:1859	compensated cardiac function	1832:1859	compensated cardiac function	1832:1859	Conclusions O-GlcNAcylation promotes compensated cardiac function in both early and established pathological hypertrophy.
31131693	8	52	theme	transverse	1422:1431	arg1	constriction					1440:1451	transverse aortic constriction	1422:1451	transverse aortic constriction	1422:1451	In both groups, OGTKO with transverse aortic constriction caused significant left ventricular dysfunction.
31131693	13	53	theme	calcium	2013:2019	arg1	handling					2021:2028	calcium handling	2013:2028	calcium handling	2013:2028	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	13	54	theme	catalytic	1975:1983	arg1	subunit					1985:1991	protein kinase A catalytic subunit	1958:1991	protein kinase A catalytic subunit	1958:1991	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	5	55	theme	O-GlcNAc	1022:1029	arg1	deficiency					1043:1052	O-GlcNAc transferase deficiency	1022:1052	O-GlcNAc transferase deficiency	1022:1052	O-GlcNAc transferase deficiency was induced at different times.
31131693	12	56	theme	Conclusions	1795:1805	arg1	O-GlcNAcylation					1807:1821	Conclusions O-GlcNAcylation	1795:1821	Conclusions O-GlcNAcylation	1795:1821	Conclusions O-GlcNAcylation promotes compensated cardiac function in both early and established pathological hypertrophy.
31131693	8	57	theme	significant	1460:1470	arg1	dysfunction					1489:1499	significant left ventricular dysfunction	1460:1499	significant left ventricular dysfunction	1460:1499	In both groups, OGTKO with transverse aortic constriction caused significant left ventricular dysfunction.
31131693	6	58	theme	pressure	1122:1129	arg1	overload					1131:1138	pressure overload	1122:1138	pressure overload	1122:1138	To evaluate the initial response to pressure overload, OGTKO was completed preoperatively and mice were followed for 2 weeks post-surgery.
31131693	3	59	theme	sustained	664:672	arg1	elevations					674:683	sustained elevations	664:683	sustained elevations during established pathological hypertrophy	664:727	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	4	60	theme	Transverse	834:843	arg1	constriction					852:863	Transverse aortic constriction	834:863	Transverse aortic constriction	834:863	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	11	61	theme	protein	1709:1715	arg1	kinase					1717:1722	protein kinase A catalytic subunit, a kinase for phospholamban,	1709:1771	kinase	1717:1722	O-GlcNAcylation of protein kinase A catalytic subunit, a kinase for phospholamban, decreased with OGTKO.
31131693	11	61	theme	protein	1709:1715	arg1	kinase					1747:1752	a kinase	1745:1752	a kinase for phospholamban	1745:1770	O-GlcNAcylation of protein kinase A catalytic subunit, a kinase for phospholamban, decreased with OGTKO.
31131693	0	62	theme	A	78:78	arg1	O-GlcNAcylation					80:94	Protein Kinase A O-GlcNAcylation	63:94	Protein Kinase A O-GlcNAcylation	63:94	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	3	63	theme	pathological	704:715	arg1	hypertrophy					717:727	established pathological hypertrophy	692:727	established pathological hypertrophy	692:727	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	5	64	theme	transferase	1031:1041	arg1	deficiency					1043:1052	O-GlcNAc transferase deficiency	1022:1052	O-GlcNAc transferase deficiency	1022:1052	O-GlcNAc transferase deficiency was induced at different times.
31131693	1	65	theme	Protein	185:191	arg1	modifications					211:223	Background Protein posttranslational modifications	174:223	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc)	174:268	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	13	66	theme	protein	1958:1964	arg1	subunit					1985:1991	protein kinase A catalytic subunit	1958:1991	protein kinase A catalytic subunit	1958:1991	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	13	67	theme	A	1973:1973	arg1	subunit					1985:1991	protein kinase A catalytic subunit	1958:1991	protein kinase A catalytic subunit	1958:1991	We identified a novel O-GlcNAcylation of protein kinase A catalytic subunit, which may regulate calcium handling and cardiac function.
31131693	2	68	theme	other	381:385	arg1	organs					387:392	other organs	381:392	other organs	381:392	In other organs, O-GlcNAc promotes adaptation to acute physiological stressors; however, prolonged O-GlcNAc elevations are believed to be detrimental.
31131693	0	69	theme	Pathological	125:136	arg1	Hypertrophy					138:148	Early and Established Pathological Hypertrophy	103:148	Early and Established Pathological Hypertrophy From Pressure Overload	103:171	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	4	70	dep	Methods	814:820	arg1	constriction					852:863	Transverse aortic constriction	834:863	Transverse aortic constriction	834:863	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	4	70	dep	Methods	814:820	arg1	surgeries					873:881	sham surgeries	868:881	sham surgeries	868:881	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	12	71	theme	pathological	1891:1902	arg1	hypertrophy					1904:1914	both early and established pathological hypertrophy	1864:1914	both early and established pathological hypertrophy	1864:1914	Conclusions O-GlcNAcylation promotes compensated cardiac function in both early and established pathological hypertrophy.
31131693	4	72	theme	sham	868:871	arg1	surgeries					873:881	sham surgeries	868:881	sham surgeries	868:881	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	2	73	theme	physiological	433:445	arg1	stressors					447:455	acute physiological stressors	427:455	acute physiological stressors	427:455	In other organs, O-GlcNAc promotes adaptation to acute physiological stressors; however, prolonged O-GlcNAc elevations are believed to be detrimental.
31131693	0	74	theme	Compensated	30:40	arg1	Function					50:57	Compensated Cardiac Function	30:57	Compensated Cardiac Function	30:57	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	2	75	theme	O-GlcNAc	477:484	arg1	elevations					486:495	prolonged O-GlcNAc elevations	467:495	prolonged O-GlcNAc elevations	467:495	In other organs, O-GlcNAc promotes adaptation to acute physiological stressors; however, prolonged O-GlcNAc elevations are believed to be detrimental.
31131693	9	76	theme	handling	1545:1552	arg1	SERCA2a					1562:1568	the calcium handling protein SERCA2a	1533:1568	the calcium handling protein SERCA2a	1533:1568	OGTKO did not affect levels of the calcium handling protein SERCA2a.
31131693	3	77	theme	cardiac	747:753	arg1	function					755:762	cardiac function	747:762	cardiac function	747:762	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	4	78	theme	transferase	961:971	arg1	mice					990:993	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	7	79	theme	6 weeks	1373:1379	arg1	post-surgery					1381:1392	6 weeks post-surgery	1373:1392	6 weeks post-surgery	1373:1392	To assess prolonged O-GlcNAcylation during established hypertrophy, OGTKO was performed starting 18 days after surgery and mice were followed until 6 weeks post-surgery.
31131693	0	80	theme	Protein	63:69	arg1	A					78:78	Protein Kinase A	63:78	Protein Kinase A O-GlcNAcylation	63:94	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	6	81	theme	initial	1102:1108	arg1	response					1110:1117	the initial response	1098:1117	the initial response to pressure overload	1098:1138	To evaluate the initial response to pressure overload, OGTKO was completed preoperatively and mice were followed for 2 weeks post-surgery.
31131693	3	82	theme	handling	795:802	arg1	proteins					804:811	calcium handling proteins	787:811	calcium handling proteins	787:811	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	0	83	from	Overload	164:171	arg1	Hypertrophy					138:148	Early and Established Pathological Hypertrophy	103:148	Early and Established Pathological Hypertrophy From Pressure Overload	103:171	O-GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O-GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload.
31131693	4	84	theme	cardiac-specific	924:939	arg1	transferase					961:971	cardiac-specific, inducible O-GlcNAc transferase	924:971	cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice	924:993	Methods and Results Transverse aortic constriction or sham surgeries were performed on littermate controls or cardiac-specific, inducible O-GlcNAc transferase knockout (OGTKO) mice to reduce O-GlcNAc levels.
31131693	3	85	theme	early	549:553	arg1	O-GlcNAcylation					555:569	early O-GlcNAcylation	549:569	early O-GlcNAcylation	549:569	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
31131693	1	86	theme	cardiac	284:290	arg1	hypertrophy					292:302	cardiac hypertrophy	284:302	cardiac hypertrophy	284:302	Background Protein posttranslational modifications by O-linked β-N-acetylglucosamine (O-GlcNAc) increase with cardiac hypertrophy, yet the functional effects of these changes are incompletely understood.
31131693	3	87	theme	initial	604:610	arg1	response					612:619	initial response	604:619	initial response to pressure overload hypertrophy	604:652	We hypothesize that early O-GlcNAcylation improves cardiac function during initial response to pressure overload hypertrophy, but that sustained elevations during established pathological hypertrophy negatively impact cardiac function by adversely affecting calcium handling proteins.
30770249	5	0	theme	protein	837:843	arg1	O-GlcNAcylation					845:859	protein O-GlcNAcylation	837:859	protein O-GlcNAcylation	837:859	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	7	1	theme	immune	1268:1273	arg1	activation					1280:1289	innate immune cell activation	1261:1289	innate immune cell activation	1261:1289	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	6	2	theme	kinase	1010:1015	arg1	RIPK3					1017:1021	the serine-threonine kinase RIPK3	989:1021	the serine-threonine kinase RIPK3	989:1021	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	6	3	theme	downstream	1124:1133	arg1	immunity					1142:1149	downstream innate immunity	1124:1149	downstream innate immunity	1124:1149	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	4	4	theme	elevated	590:597	arg1	activities					599:608	elevated activities	590:608	elevated activities of glycolysis and the pentose phosphate pathway	590:656	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	7	5	theme	cell	1275:1278	arg1	activation					1280:1289	innate immune cell activation	1261:1289	innate immune cell activation	1261:1289	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	6	6	theme	RIPK3	1017:1021	arg1	O-GlcNAcylation					970:984	OGT-mediated O-GlcNAcylation	957:984	OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467)	957:1045	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	2	7	theme	cell	324:327	arg1	activation					329:338	immune cell activation	317:338	immune cell activation	317:338	However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood.
30770249	4	8	theme	macrophages	673:683	arg1	activation					659:668	activation	659:668	activation of macrophages with lipopolysaccharide (LPS)	659:713	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	5	9	theme	immune	885:890	arg1	activation					892:901	innate immune activation	878:901	innate immune activation	878:901	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	7	10	theme	innate	1261:1266	arg1	activation					1280:1289	innate immune cell activation	1261:1289	innate immune cell activation	1261:1289	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	2	11	theme	immune	317:322	arg1	activation					329:338	immune cell activation	317:338	immune cell activation	317:338	However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood.
30770249	6	12	theme	serine-threonine	993:1008	arg1	RIPK3					1017:1021	the serine-threonine kinase RIPK3	989:1021	the serine-threonine kinase RIPK3	989:1021	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	5	13	theme	septic	919:924	arg1	inflammation					926:937	exacerbated septic inflammation	907:937	exacerbated septic inflammation	907:937	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	5	14	theme	innate	878:883	arg1	activation					892:901	innate immune activation	878:901	innate immune activation	878:901	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	4	15	theme	protein	755:761	arg1	O-GlcNAcylation					763:777	protein O-GlcNAcylation	755:777	protein O-GlcNAcylation	755:777	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	1	16	theme	many	207:210	arg1	diseases					225:232	many inflammatory diseases	207:232	many inflammatory diseases	207:232	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	1	16	theme	many	207:210	arg1	sepsis					243:248	sepsis	243:248	sepsis	243:248	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	5	17	theme	key	822:824	arg1	transferase					801:811	O-GlcNAc transferase	792:811	O-GlcNAc transferase (OGT)	792:817	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	5	17	theme	key	822:824	arg1	enzyme					826:831	a key enzyme	820:831	a key enzyme for protein O-GlcNAcylation	820:859	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	2	18	theme	pathways	301:308	arg1	role					264:267	the role	260:267	the role of individual glucose metabolic pathways during immune cell activation and inflammation	260:355	However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood.
30770249	3	19	theme	signaling	513:521	arg1	function					455:462	a previously unrecognized anti-inflammatory function	411:462	a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP)	411:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	3	20	theme	anti-inflammatory	437:453	arg1	function					455:462	a previously unrecognized anti-inflammatory function	411:462	a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP)	411:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	6	21	theme	RIPK3-RIPK1	1057:1067	arg1	hetero-					1069:1075	RIPK3-RIPK1 hetero-	1057:1075	RIPK3-RIPK1 hetero-	1057:1075	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	7	22	theme	immuno-metabolic	1208:1223	arg1	crosstalk					1225:1233	an immuno-metabolic crosstalk	1205:1233	an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation	1205:1289	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	4	23	theme	HBP	738:740	arg1	activity					742:749	attenuated HBP activity	727:749	attenuated HBP activity	727:749	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	7	24	theme	glucose	1324:1330	arg1	metabolism					1332:1341	glucose metabolism	1324:1341	glucose metabolism	1324:1341	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	1	25	theme	diseases	225:232	arg1	feature					196:202	a hallmark feature	185:202	a hallmark feature of many inflammatory diseases, such as sepsis	185:248	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	0	26	theme	O-GlcNAc	0:7	arg1	Transferase					9:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3.
30770249	4	27	theme	pentose	632:638	arg1	pathway					650:656	the pentose phosphate pathway	628:656	the pentose phosphate pathway	628:656	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	1	28	theme	Elevated	130:137	arg1	metabolism					147:156	Elevated glucose metabolism	130:156	Elevated glucose metabolism in immune cells	130:172	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	7	29	from	importance	1310:1319	arg1	inflammation					1353:1364	septic inflammation	1346:1364	septic inflammation	1346:1364	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	6	30	from	O-GlcNAcylation	970:984	arg1	threonine					1026:1034	threonine 467	1026:1038	threonine 467 (T467)	1026:1045	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	6	30	from	O-GlcNAcylation	970:984	arg1	T467					1041:1044	T467	1041:1044	T467	1041:1044	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	4	31	with	activation	659:668	arg1	lipopolysaccharide					690:707	lipopolysaccharide	690:707	lipopolysaccharide (LPS)	690:713	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	4	31	with	activation	659:668	arg1	LPS					710:712	LPS	710:712	LPS	710:712	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	5	32	theme	O-GlcNAc	792:799	arg1	transferase					801:811	O-GlcNAc transferase	792:811	O-GlcNAc transferase (OGT)	792:817	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	5	32	theme	O-GlcNAc	792:799	arg1	enzyme					826:831	a key enzyme	820:831	a key enzyme for protein O-GlcNAcylation	820:859	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	5	32	theme	O-GlcNAc	792:799	arg1	OGT					814:816	OGT	814:816	OGT	814:816	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	1	33	theme	glucose	139:145	arg1	metabolism					147:156	Elevated glucose metabolism	130:156	Elevated glucose metabolism in immune cells	130:172	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	5	34	theme	exacerbated	907:917	arg1	inflammation					926:937	exacerbated septic inflammation	907:937	exacerbated septic inflammation	907:937	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	3	35	theme	unrecognized	424:435	arg1	function					455:462	a previously unrecognized anti-inflammatory function	411:462	a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP)	411:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	4	36	theme	pathway	650:656	arg1	activities					599:608	elevated activities	590:608	elevated activities of glycolysis and the pentose phosphate pathway	590:656	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	5	37	theme	transferase	801:811	arg1	Deletion					780:787	Deletion	780:787	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation,	780:860	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	3	38	theme	hexosamine	543:552	arg1	HBP					576:578	HBP	576:578	HBP	576:578	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	3	38	theme	hexosamine	543:552	arg1	pathway					567:573	the hexosamine biosynthesis pathway	539:573	the hexosamine biosynthesis pathway (HBP)	539:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	3	39	theme	O-linked	471:478	arg1	O-GlcNAc					503:510	O-GlcNAc	503:510	O-GlcNAc	503:510	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	3	39	theme	O-linked	471:478	arg1	β-N-acetylglucosamine					480:500	O-linked β-N-acetylglucosamine	471:500	the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP)	467:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	4	40	theme	phosphate	640:648	arg1	pathway					650:656	the pentose phosphate pathway	628:656	the pentose phosphate pathway	628:656	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	6	41	theme	OGT-mediated	957:968	arg1	O-GlcNAcylation					970:984	OGT-mediated O-GlcNAcylation	957:984	OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467)	957:1045	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	4	42	theme	attenuated	727:736	arg1	activity					742:749	attenuated HBP activity	727:749	attenuated HBP activity	727:749	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	3	43	theme	β-N-acetylglucosamine	480:500	arg1	signaling					513:521	the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling	467:521	the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP)	467:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	7	44	theme	septic	1346:1351	arg1	inflammation					1353:1364	septic inflammation	1346:1364	septic inflammation	1346:1364	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	3	45	link	O-linked	471:478	arg1	O-GlcNAc					503:510	O-GlcNAc	503:510	O-GlcNAc	503:510	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	3	45	link	O-linked	471:478	arg1	β-N-acetylglucosamine					480:500	O-linked β-N-acetylglucosamine	471:500	the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP)	467:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	5	46	theme	enhanced	869:876	arg1	activation					892:901	innate immune activation	878:901	innate immune activation	878:901	Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation.
30770249	1	47	theme	immune	161:166	arg1	cells					168:172	immune cells	161:172	immune cells	161:172	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	4	48	theme	glycolysis	613:622	arg1	activities					599:608	elevated activities	590:608	elevated activities of glycolysis and the pentose phosphate pathway	590:656	Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation.
30770249	2	49	theme	metabolic	291:299	arg1	pathways					301:308	individual glucose metabolic pathways	272:308	individual glucose metabolic pathways	272:308	However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood.
30770249	7	50	theme	essential	1235:1243	arg1	crosstalk					1225:1233	an immuno-metabolic crosstalk	1205:1233	an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation	1205:1289	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	3	51	theme	biosynthesis	554:565	arg1	HBP					576:578	HBP	576:578	HBP	576:578	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	3	51	theme	biosynthesis	554:565	arg1	pathway					567:573	the hexosamine biosynthesis pathway	539:573	the hexosamine biosynthesis pathway (HBP)	539:579	Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP).
30770249	1	52	from	metabolism	147:156	arg1	cells					168:172	immune cells	161:172	immune cells	161:172	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	6	53	theme	necroptosis	1155:1165	arg1	signaling					1167:1175	necroptosis signaling	1155:1175	necroptosis signaling	1155:1175	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	2	54	theme	glucose	283:289	arg1	pathways					301:308	individual glucose metabolic pathways	272:308	individual glucose metabolic pathways	272:308	However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood.
30770249	0	55	theme	Serine/Threonine-Protein	95:118	arg1	Kinase					120:125	Receptor-Interacting Serine/Threonine-Protein Kinase 3	74:127	Receptor-Interacting Serine/Threonine-Protein Kinase 3	74:127	O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3.
30770249	2	56	theme	individual	272:281	arg1	pathways					301:308	individual glucose metabolic pathways	272:308	individual glucose metabolic pathways	272:308	However, the role of individual glucose metabolic pathways during immune cell activation and inflammation remains incompletely understood.
30770249	1	57	theme	inflammatory	212:223	arg1	diseases					225:232	many inflammatory diseases	207:232	many inflammatory diseases	207:232	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	1	57	theme	inflammatory	212:223	arg1	sepsis					243:248	sepsis	243:248	sepsis	243:248	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	0	58	theme	Receptor-Interacting	74:93	arg1	Kinase					120:125	Receptor-Interacting Serine/Threonine-Protein Kinase 3	74:127	Receptor-Interacting Serine/Threonine-Protein Kinase 3	74:127	O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3.
30770249	6	59	theme	RIPK3-RIPK3	1081:1091	arg1	homo-interaction					1093:1108	RIPK3-RIPK3 homo-interaction	1081:1108	RIPK3-RIPK3 homo-interaction	1081:1108	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30770249	1	60	theme	hallmark	187:194	arg1	feature					196:202	a hallmark feature	185:202	a hallmark feature of many inflammatory diseases, such as sepsis	185:248	Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis.
30770249	7	61	theme	metabolism	1332:1341	arg1	importance					1310:1319	the importance	1306:1319	the importance of glucose metabolism in septic inflammation	1306:1364	Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
30770249	6	62	theme	innate	1135:1140	arg1	immunity					1142:1149	downstream innate immunity	1124:1149	downstream innate immunity	1124:1149	Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling.
30664665	0	0	theme	protein	76:82	arg1	O-GlcNAcylation					84:98	protein O-GlcNAcylation	76:98	protein O-GlcNAcylation	76:98	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	2	1	theme	Treg	461:464	arg1	homeostasis					471:481	Treg cell homeostasis	461:481	Treg cell homeostasis	461:481	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	4	2	theme	reduced	777:783	arg1	expression					791:800	modestly reduced FOXP3 expression	768:800	modestly reduced FOXP3 expression	768:800	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	5	3	theme	STAT5	1042:1046	arg1	form					1034:1037	a constitutively active form	1010:1037	a constitutively active form of STAT5	1010:1046	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	4	4	theme	O-GlcNAc-deficient	709:726	arg1	cells					733:737	O-GlcNAc-deficient Treg cells	709:737	O-GlcNAc-deficient Treg cells	709:737	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	5	5	theme	IL-2/STAT5	964:973	arg1	signaling					975:983	IL-2/STAT5 signaling	964:983	IL-2/STAT5 signaling	964:983	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	3	6	theme	signaling	689:697	arg1	pathways					699:706	these critical signaling pathways	674:706	these critical signaling pathways	674:706	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	5	7	theme	protein	929:935	arg1	O-GlcNAcylation					937:951	protein O-GlcNAcylation	929:951	protein O-GlcNAcylation	929:951	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	1	8	theme	inflammatory	151:162	arg1	responses					164:172	inflammatory responses	151:172	inflammatory responses	151:172	Regulatory T (Treg) cells control self-tolerance, inflammatory responses and tissue homeostasis.
30664665	4	9	theme	impaired	812:819	arg1	stability					829:837	strongly impaired lineage stability	803:837	strongly impaired lineage stability	803:837	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	5	10	from	deficiency	915:924	arg1	O-GlcNAcylation					937:951	protein O-GlcNAcylation	929:951	protein O-GlcNAcylation	929:951	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	2	11	theme	T	284:284	arg1	receptor					291:298	T cell receptor	284:298	T cell receptor (TCR) signaling	284:314	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	11	theme	T	284:284	arg1	TCR					301:303	TCR	301:303	TCR	301:303	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	12	theme	cell	286:289	arg1	receptor					291:298	T cell receptor	284:298	T cell receptor (TCR) signaling	284:314	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	12	theme	cell	286:289	arg1	TCR					301:303	TCR	301:303	TCR	301:303	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	5	13	theme	active	1027:1032	arg1	form					1034:1037	a constitutively active form	1010:1037	a constitutively active form of STAT5	1010:1046	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	4	14	from	expression	791:800	arg1	mice					899:902	mice	899:902	mice	899:902	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	4	15	theme	FOXP3	785:789	arg1	expression					791:800	modestly reduced FOXP3 expression	768:800	modestly reduced FOXP3 expression	768:800	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	5	16	from	inflammation	1105:1116	arg1	mice					1140:1143	O-GlcNAc deficient mice	1121:1143	O-GlcNAc deficient mice	1121:1143	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	4	17	from	autoimmunity	883:894	arg1	mice					899:902	mice	899:902	mice	899:902	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	4	18	theme	fatal	877:881	arg1	autoimmunity					883:894	ultimately fatal autoimmunity	866:894	ultimately fatal autoimmunity in mice	866:902	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	5	19	theme	form	1034:1037	arg1	overexpression					992:1005	overexpression	992:1005	overexpression of a constitutively active form of STAT5	992:1046	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	2	20	theme	suppressive	370:380	arg1	function					391:398	the suppressive effector function	366:398	the suppressive effector function of Treg cells	366:412	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	6	21	theme	lineage	1227:1233	arg1	stability					1235:1243	lineage stability	1227:1243	lineage stability	1227:1243	Collectively, our data demonstrate that protein O-GlcNAcylation is essential for lineage stability and effector function in Treg cells.
30664665	6	22	theme	effector	1249:1256	arg1	function					1258:1265	effector function	1249:1265	effector function	1249:1265	Collectively, our data demonstrate that protein O-GlcNAcylation is essential for lineage stability and effector function in Treg cells.
30664665	0	23	theme	lineage	4:10	arg1	stability					12:20	lineage stability	4:20	lineage stability	4:20	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	3	24	theme	posttranslational	545:561	arg1	modification					563:574	TCR-activated posttranslational modification	531:574	TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc)	531:617	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	1	25	theme	tissue	178:183	arg1	homeostasis					185:195	tissue homeostasis	178:195	tissue homeostasis	178:195	Regulatory T (Treg) cells control self-tolerance, inflammatory responses and tissue homeostasis.
30664665	3	26	theme	TCR-activated	531:543	arg1	modification					563:574	TCR-activated posttranslational modification	531:574	TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc)	531:617	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	3	27	theme	O-linked	579:586	arg1	N-Acetylglucosamine					588:606	O-linked N-Acetylglucosamine	579:606	O-linked N-Acetylglucosamine (O-GlcNAc)	579:617	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	3	27	theme	O-linked	579:586	arg1	O-GlcNAc					609:616	O-GlcNAc	609:616	O-GlcNAc	609:616	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	2	28	theme	receptor	291:298	arg1	signaling					306:314	T cell receptor (TCR) signaling	284:314	T cell receptor (TCR) signaling	284:314	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	29	theme	Treg	403:406	arg1	cells					408:412	Treg cells	403:412	Treg cells	403:412	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	30	theme	cells	408:412	arg1	function					391:398	the suppressive effector function	366:398	the suppressive effector function of Treg cells	366:412	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	6	31	theme	Treg	1270:1273	arg1	cells					1275:1279	Treg cells	1270:1279	Treg cells	1270:1279	Collectively, our data demonstrate that protein O-GlcNAcylation is essential for lineage stability and effector function in Treg cells.
30664665	1	32	theme	T	112:112	arg1	cells					121:125	Regulatory T (Treg) cells	101:125	Regulatory T (Treg) cells	101:125	Regulatory T (Treg) cells control self-tolerance, inflammatory responses and tissue homeostasis.
30664665	6	33	from	stability	1235:1243	arg1	cells					1275:1279	Treg cells	1270:1279	Treg cells	1270:1279	Collectively, our data demonstrate that protein O-GlcNAcylation is essential for lineage stability and effector function in Treg cells.
30664665	4	34	theme	Treg	728:731	arg1	cells					733:737	O-GlcNAc-deficient Treg cells	709:737	O-GlcNAc-deficient Treg cells	709:737	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	6	35	from	function	1258:1265	arg1	cells					1275:1279	Treg cells	1270:1279	Treg cells	1270:1279	Collectively, our data demonstrate that protein O-GlcNAcylation is essential for lineage stability and effector function in Treg cells.
30664665	5	36	theme	cell	1075:1078	arg1	dysfunction					1080:1090	Treg cell dysfunction	1070:1090	Treg cell dysfunction	1070:1090	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	5	37	from	dysfunction	1080:1090	arg1	mice					1140:1143	O-GlcNAc deficient mice	1121:1143	O-GlcNAc deficient mice	1121:1143	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	5	38	theme	systemic	1096:1103	arg1	inflammation					1105:1116	systemic inflammation	1096:1116	systemic inflammation	1096:1116	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	0	39	theme	suppressive	26:36	arg1	program					38:44	suppressive program	26:44	suppressive program	26:44	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	3	40	link	O-linked	579:586	arg1	N-Acetylglucosamine					588:606	O-linked N-Acetylglucosamine	579:606	O-linked N-Acetylglucosamine (O-GlcNAc)	579:617	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	3	40	link	O-linked	579:586	arg1	O-GlcNAc					609:616	O-GlcNAc	609:616	O-GlcNAc	609:616	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	2	41	theme	continued	220:228	arg1	expression					230:239	continued expression	220:239	continued expression of FOXP3	220:248	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	42	theme	effector	382:389	arg1	function					391:398	the suppressive effector function	366:398	the suppressive effector function of Treg cells	366:412	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	0	43	theme	regulatory	49:58	arg1	cells					62:66	regulatory T cells	49:66	regulatory T cells	49:66	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	0	44	theme	T	60:60	arg1	cells					62:66	regulatory T cells	49:66	regulatory T cells	49:66	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	2	45	theme	interleukin-2	320:332	arg1	activation					347:356	interleukin-2 (IL-2)/STAT5 activation	320:356	interleukin-2 (IL-2)/STAT5 activation	320:356	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	46	dep	control	453:459	arg1	remains					496:502	remains	496:502	remains unclear	496:510	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	47	theme	Treg	208:211	arg1	cells					213:217	mature Treg cells	201:217	mature Treg cells	201:217	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	3	48	theme	critical	680:687	arg1	pathways					699:706	these critical signaling pathways	674:706	these critical signaling pathways	674:706	Here we show that TCR-activated posttranslational modification by O-linked N-Acetylglucosamine (O-GlcNAc) stabilizes FOXP3 and activates STAT5, thus integrating these critical signaling pathways.
30664665	4	49	from	function	852:859	arg1	mice					899:902	mice	899:902	mice	899:902	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	1	50	theme	Treg	115:118	arg1	cells					121:125	Regulatory T (Treg) cells	101:125	Regulatory T (Treg) cells	101:125	Regulatory T (Treg) cells control self-tolerance, inflammatory responses and tissue homeostasis.
30664665	2	51	theme	mature	201:206	arg1	cells					213:217	mature Treg cells	201:217	mature Treg cells	201:217	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	52	theme	lineage	260:266	arg1	identity					268:275	lineage identity	260:275	lineage identity	260:275	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	4	53	theme	effector	843:850	arg1	function					852:859	effector function	843:859	effector function	843:859	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	1	54	theme	Regulatory	101:110	arg1	cells					121:125	Regulatory T (Treg) cells	101:125	Regulatory T (Treg) cells	101:125	Regulatory T (Treg) cells control self-tolerance, inflammatory responses and tissue homeostasis.
30664665	0	55	dep	stability	12:20	arg1	The					0:2	The	0:2	The	0:2	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	6	56	theme	protein	1186:1192	arg1	O-GlcNAcylation					1194:1208	protein O-GlcNAcylation	1186:1208	protein O-GlcNAcylation	1186:1208	Collectively, our data demonstrate that protein O-GlcNAcylation is essential for lineage stability and effector function in Treg cells.
30664665	4	57	theme	lineage	821:827	arg1	stability					829:837	strongly impaired lineage stability	803:837	strongly impaired lineage stability	803:837	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	0	58	theme	cells	62:66	arg1	stability					12:20	lineage stability	4:20	lineage stability	4:20	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	0	58	theme	cells	62:66	arg1	program					38:44	suppressive program	26:44	suppressive program	26:44	The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation.
30664665	5	59	theme	deficient	1130:1138	arg1	mice					1140:1143	O-GlcNAc deficient mice	1121:1143	O-GlcNAc deficient mice	1121:1143	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30664665	2	60	theme	FOXP3	244:248	arg1	expression					230:239	continued expression	220:239	continued expression of FOXP3	220:248	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	4	61	from	stability	829:837	arg1	mice					899:902	mice	899:902	mice	899:902	O-GlcNAc-deficient Treg cells develop normally but display modestly reduced FOXP3 expression, strongly impaired lineage stability and effector function, and ultimately fatal autoimmunity in mice.
30664665	2	62	theme	/STAT5	340:345	arg1	activation					347:356	interleukin-2 (IL-2)/STAT5 activation	320:356	interleukin-2 (IL-2)/STAT5 activation	320:356	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	2	63	theme	cell	466:469	arg1	homeostasis					471:481	Treg cell homeostasis	461:481	Treg cell homeostasis	461:481	In mature Treg cells, continued expression of FOXP3 maintains lineage identity, while T cell receptor (TCR) signaling and interleukin-2 (IL-2)/STAT5 activation support the suppressive effector function of Treg cells, but how these regulators synergize to control Treg cell homeostasis and function remains unclear.
30664665	5	64	theme	Treg	1070:1073	arg1	dysfunction					1080:1090	Treg cell dysfunction	1070:1090	Treg cell dysfunction	1070:1090	Moreover, deficiency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitutively active form of STAT5 partially ameliorates Treg cell dysfunction and systemic inflammation in O-GlcNAc deficient mice.
30543776	5	0	theme	antiviral	828:836	arg1	responses					845:853	defective antiviral immune responses	818:853	defective antiviral immune responses	818:853	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	6	1	theme	inducible	1072:1080	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	5	2	theme	Human	713:717	arg1	cells					730:734	Human and murine cells	713:734	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation,	713:811	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	1	3	theme	hallmark	156:163	arg1	metabolism					108:117	Increased glucose metabolism	90:117	Increased glucose metabolism in immune cells	90:133	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	1	3	theme	hallmark	156:163	arg1	feature					165:171	a hallmark feature	154:171	a hallmark feature of acute inflammation	154:193	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	7	4	theme	molecular	1163:1171	arg1	mechanism					1173:1181	a molecular mechanism	1161:1181	a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function	1161:1243	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	5	5	theme	immune	838:843	arg1	responses					845:853	defective antiviral immune responses	818:853	defective antiviral immune responses	818:853	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	6	6	theme	K63-linked	998:1007	arg1	ubiquitination					1009:1022	K63-linked ubiquitination	998:1022	K63-linked ubiquitination of MAVS	998:1030	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	6	7	theme	O-GlcNAc	892:899	arg1	O-GlcNAcylation					922:936	O-GlcNAc transferase-mediated O-GlcNAcylation	892:936	O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366	892:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	5	8	theme	VSV	860:862	arg1	challenge					864:872	VSV challenge	860:872	VSV challenge	860:872	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	1	9	theme	tissue	273:278	arg1	damage					280:285	tissue damage	273:285	tissue damage	273:285	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	5	10	theme	murine	723:728	arg1	cells					730:734	Human and murine cells	713:734	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation,	713:811	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	3	11	theme	essential	418:426	arg1	function					428:435	an essential function	415:435	an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity	415:582	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	2	12	theme	metabolic	328:336	arg1	pathways					338:345	individual glucose metabolic pathways	309:345	individual glucose metabolic pathways	309:345	However, the role of individual glucose metabolic pathways during viral infection remains largely unknown.
30543776	3	13	link	O-linked	493:500	arg1	O-GlcNAc					525:532	O-GlcNAc	525:532	O-GlcNAc	525:532	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	3	13	link	O-linked	493:500	arg1	β-N-acetylglucosamine					502:522	O-linked β-N-acetylglucosamine	493:522	the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling	440:543	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	0	14	attach	Links	21:25	arg1	Immunity					80:87	MAVS-Mediated Antiviral Innate Immunity	49:87	MAVS-Mediated Antiviral Innate Immunity	49:87	O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.
30543776	0	14	attach	Links	21:25	arg2	Transferase					9:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.
30543776	1	15	dep	serves	144:149	arg1	affects					215:221	affects	215:221	affects disease outcome following bacterial infection and tissue damage	215:285	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	6	16	theme	-antiviral	1101:1110	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	4	17	theme	downstream	677:686	arg1	O-GlcNAcylation					696:710	downstream protein O-GlcNAcylation	677:710	downstream protein O-GlcNAcylation	677:710	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	3	18	theme	innate	568:573	arg1	immunity					575:582	antiviral innate immunity	558:582	antiviral innate immunity	558:582	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	3	19	theme	hexosamine	444:453	arg1	pathway					468:474	the hexosamine biosynthesis pathway	440:474	the hexosamine biosynthesis pathway (HBP)	440:480	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	3	19	theme	hexosamine	444:453	arg1	HBP					477:479	HBP	477:479	HBP	477:479	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	6	20	link	K63-linked	998:1007	arg1	ubiquitination					1009:1022	K63-linked ubiquitination	998:1022	K63-linked ubiquitination of MAVS	998:1030	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	7	21	theme	glucose	1278:1284	arg1	metabolism					1286:1295	glucose metabolism	1278:1295	glucose metabolism	1278:1295	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	6	22	from	O-GlcNAcylation	922:936	arg1	serine					971:976	serine 366	971:980	serine 366	971:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	6	23	theme	signaling	945:953	arg1	MAVS					963:966	the signaling adaptor MAVS	941:966	the signaling adaptor MAVS on serine 366	941:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	1	24	theme	Increased	90:98	arg1	metabolism					108:117	Increased glucose metabolism	90:117	Increased glucose metabolism in immune cells	90:133	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	1	24	theme	Increased	90:98	arg1	feature					165:171	a hallmark feature	154:171	a hallmark feature of acute inflammation	154:193	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	1	25	theme	acute	176:180	arg1	inflammation					182:193	acute inflammation	176:193	acute inflammation	176:193	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	6	26	theme	retinoic-acid	1058:1070	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	6	27	theme	receptor	1092:1099	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	1	28	theme	glucose	100:106	arg1	metabolism					108:117	Increased glucose metabolism	90:117	Increased glucose metabolism in immune cells	90:133	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	1	28	theme	glucose	100:106	arg1	feature					165:171	a hallmark feature	154:171	a hallmark feature of acute inflammation	154:193	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	1	29	theme	inflammation	182:193	arg1	metabolism					108:117	Increased glucose metabolism	90:117	Increased glucose metabolism in immune cells	90:133	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	1	29	theme	inflammation	182:193	arg1	feature					165:171	a hallmark feature	154:171	a hallmark feature of acute inflammation	154:193	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	0	30	theme	O-GlcNAc	0:7	arg1	Transferase					9:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase	0:19	O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.
30543776	4	31	theme	macrophages with	598:613	arg1	VSVs					645:648	VSVs	645:648	VSVs	645:648	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	4	31	theme	macrophages with	598:613	arg1	viruses					636:642	macrophages with vesicular stomatitis viruses	598:642	macrophages with vesicular stomatitis viruses (VSVs)	598:649	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	7	32	theme	MAVS	1231:1234	arg1	function					1236:1243	MAVS function	1231:1243	MAVS function	1231:1243	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	2	33	theme	glucose	320:326	arg1	pathways					338:345	individual glucose metabolic pathways	309:345	individual glucose metabolic pathways	309:345	However, the role of individual glucose metabolic pathways during viral infection remains largely unknown.
30543776	3	34	theme	biosynthesis	455:466	arg1	pathway					468:474	the hexosamine biosynthesis pathway	440:474	the hexosamine biosynthesis pathway (HBP)	440:480	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	3	34	theme	biosynthesis	455:466	arg1	HBP					477:479	HBP	477:479	HBP	477:479	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	0	35	theme	Glucose	27:33	arg1	Metabolism					35:44	Glucose Metabolism	27:44	Glucose Metabolism	27:44	O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.
30543776	6	36	theme	gene-like	1082:1090	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	7	37	theme	HBP-mediated	1192:1203	arg1	O-GlcNAcylation					1205:1219	HBP-mediated O-GlcNAcylation	1192:1219	HBP-mediated O-GlcNAcylation	1192:1219	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	2	38	theme	individual	309:318	arg1	pathways					338:345	individual glucose metabolic pathways	309:345	individual glucose metabolic pathways	309:345	However, the role of individual glucose metabolic pathways during viral infection remains largely unknown.
30543776	3	39	theme	-associated	481:491	arg1	signaling					535:543	the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling	440:543	the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling	440:543	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	6	40	from	MAVS	963:966	arg1	serine					971:976	serine 366	971:980	serine 366	971:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	4	41	theme	stomatitis	625:634	arg1	VSVs					645:648	VSVs	645:648	VSVs	645:648	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	4	41	theme	stomatitis	625:634	arg1	viruses					636:642	macrophages with vesicular stomatitis viruses	598:642	macrophages with vesicular stomatitis viruses (VSVs)	598:649	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	1	42	theme	immune	122:127	arg1	cells					129:133	immune cells	122:133	immune cells	122:133	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	3	43	theme	O-linked	493:500	arg1	O-GlcNAc					525:532	O-GlcNAc	525:532	O-GlcNAc	525:532	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	3	43	theme	O-linked	493:500	arg1	β-N-acetylglucosamine					502:522	O-linked β-N-acetylglucosamine	493:522	the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling	440:543	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	3	44	theme	signaling	535:543	arg1	function					428:435	an essential function	415:435	an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity	415:582	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	4	45	theme	vesicular	615:623	arg1	VSVs					645:648	VSVs	645:648	VSVs	645:648	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	4	45	theme	vesicular	615:623	arg1	viruses					636:642	macrophages with vesicular stomatitis viruses	598:642	macrophages with vesicular stomatitis viruses (VSVs)	598:649	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	5	46	theme	key	773:775	arg1	transferase					758:768	O-GlcNAc transferase	749:768	O-GlcNAc transferase	749:768	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	5	46	theme	key	773:775	arg1	enzyme					777:782	a key enzyme	771:782	a key enzyme for protein O-GlcNAcylation	771:810	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	6	47	theme	MAVS	963:966	arg1	O-GlcNAcylation					922:936	O-GlcNAc transferase-mediated O-GlcNAcylation	892:936	O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366	892:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	6	48	from	serine	971:976	arg1	O-GlcNAcylation					922:936	O-GlcNAc transferase-mediated O-GlcNAcylation	892:936	O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366	892:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	7	49	theme	antiviral	1300:1308	arg1	immunity					1317:1324	antiviral innate immunity	1300:1324	antiviral innate immunity	1300:1324	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	6	50	theme	downstream	1047:1056	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	4	51	theme	viruses	636:642	arg1	Challenge					585:593	Challenge	585:593	Challenge of macrophages with vesicular stomatitis viruses (VSVs)	585:649	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	6	52	theme	adaptor	955:961	arg1	MAVS					963:966	the signaling adaptor MAVS	941:966	the signaling adaptor MAVS on serine 366	941:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	7	53	theme	innate	1310:1315	arg1	immunity					1317:1324	antiviral innate immunity	1300:1324	antiviral innate immunity	1300:1324	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	1	54	theme	disease	223:229	arg1	outcome					231:237	disease outcome	223:237	disease outcome following bacterial infection and tissue damage	223:285	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	0	55	theme	Antiviral	63:71	arg1	Immunity					80:87	MAVS-Mediated Antiviral Innate Immunity	49:87	MAVS-Mediated Antiviral Innate Immunity	49:87	O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.
30543776	6	56	theme	subsequent	1036:1045	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	5	57	theme	deficient	736:744	arg1	cells					730:734	Human and murine cells	713:734	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation,	713:811	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	5	58	theme	defective	818:826	arg1	responses					845:853	defective antiviral immune responses	818:853	defective antiviral immune responses	818:853	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	0	59	theme	MAVS-Mediated	49:61	arg1	Immunity					80:87	MAVS-Mediated Antiviral Innate Immunity	49:87	MAVS-Mediated Antiviral Innate Immunity	49:87	O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.
30543776	7	60	from	importance	1264:1273	arg1	immunity					1317:1324	antiviral innate immunity	1300:1324	antiviral innate immunity	1300:1324	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	6	61	theme	signaling	1112:1120	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	2	62	theme	viral	354:358	arg1	infection					360:368	viral infection	354:368	viral infection	354:368	However, the role of individual glucose metabolic pathways during viral infection remains largely unknown.
30543776	6	63	theme	MAVS	1027:1030	arg1	activation					1122:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation	1036:1131	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	6	63	theme	MAVS	1027:1030	arg1	ubiquitination					1009:1022	K63-linked ubiquitination	998:1022	K63-linked ubiquitination of MAVS	998:1030	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	5	64	theme	O-GlcNAc	749:756	arg1	transferase					758:768	O-GlcNAc transferase	749:768	O-GlcNAc transferase	749:768	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	5	64	theme	O-GlcNAc	749:756	arg1	enzyme					777:782	a key enzyme	771:782	a key enzyme for protein O-GlcNAcylation	771:810	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	7	65	theme	metabolism	1286:1295	arg1	importance					1264:1273	the importance	1260:1273	the importance of glucose metabolism in antiviral innate immunity	1260:1324	Thus, our study identifies a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates MAVS function and highlights the importance of glucose metabolism in antiviral innate immunity.
30543776	3	66	theme	β-N-acetylglucosamine	502:522	arg1	signaling					535:543	the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling	440:543	the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling	440:543	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	4	67	theme	HBP	660:662	arg1	activity					664:671	HBP activity	660:671	HBP activity	660:671	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	5	68	theme	transferase	758:768	arg1	deficient					736:744	deficient	736:744	deficient	736:744	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
30543776	2	69	theme	pathways	338:345	arg1	role					301:304	the role	297:304	the role of individual glucose metabolic pathways during viral infection	297:368	However, the role of individual glucose metabolic pathways during viral infection remains largely unknown.
30543776	6	70	theme	transferase-mediated	901:920	arg1	O-GlcNAcylation					922:936	O-GlcNAc transferase-mediated O-GlcNAcylation	892:936	O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366	892:980	Mechanistically, O-GlcNAc transferase-mediated O-GlcNAcylation of the signaling adaptor MAVS on serine 366 is required for K63-linked ubiquitination of MAVS and subsequent downstream retinoic-acid inducible gene-like receptor -antiviral signaling activation.
30543776	4	71	theme	protein	688:694	arg1	O-GlcNAcylation					696:710	downstream protein O-GlcNAcylation	677:710	downstream protein O-GlcNAcylation	677:710	Challenge of macrophages with vesicular stomatitis viruses (VSVs) enhances HBP activity and downstream protein O-GlcNAcylation.
30543776	1	72	from	metabolism	108:117	arg1	cells					129:133	immune cells	122:133	immune cells	122:133	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	1	73	theme	bacterial	249:257	arg1	infection					259:267	bacterial infection	249:267	bacterial infection	249:267	Increased glucose metabolism in immune cells not only serves as a hallmark feature of acute inflammation but also profoundly affects disease outcome following bacterial infection and tissue damage.
30543776	0	74	theme	Innate	73:78	arg1	Immunity					80:87	MAVS-Mediated Antiviral Innate Immunity	49:87	MAVS-Mediated Antiviral Innate Immunity	49:87	O-GlcNAc Transferase Links Glucose Metabolism to MAVS-Mediated Antiviral Innate Immunity.
30543776	3	75	theme	antiviral	558:566	arg1	immunity					575:582	antiviral innate immunity	558:582	antiviral innate immunity	558:582	Here we demonstrate an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in promoting antiviral innate immunity.
30543776	5	76	theme	protein	788:794	arg1	O-GlcNAcylation					796:810	protein O-GlcNAcylation	788:810	protein O-GlcNAcylation	788:810	Human and murine cells deficient of O-GlcNAc transferase, a key enzyme for protein O-GlcNAcylation, show defective antiviral immune responses upon VSV challenge.
28187132	0	0	theme	pathway	89:95	arg1	genes					60:64	critical genes	51:64	critical genes of the O-glycosylation pathway	51:95	GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway.
28187132	2	1	theme	ancestry	479:486	arg1	subjects					443:450	2,633 subjects	437:450	2,633 subjects of European and East Asian ancestry	437:486	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	3	2	theme	essential	659:667	arg1	genes					627:631	These genes	621:631	These genes	621:631	These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1.
28187132	3	2	theme	essential	659:667	arg1	partners					650:657	molecular partners	640:657	molecular partners essential for enzymatic O-glycosylation of IgA1	640:705	These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1.
28187132	1	3	theme	glomerulonephritis	242:259	arg1	worldwide					261:269	glomerulonephritis worldwide	242:269	glomerulonephritis worldwide	242:269	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	0	4	theme	O-glycosylation	73:87	arg1	pathway					89:95	the O-glycosylation pathway	69:95	the O-glycosylation pathway	69:95	GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway.
28187132	7	5	from	rate	1224:1227	arg1	cells					1271:1275	IgA1-producing cells	1256:1275	IgA1-producing cells	1256:1275	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	4	6	from	%	831:831	arg1	Asians					841:846	East Asians	836:846	East Asians	836:846	We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians.
28187132	1	7	theme	worldwide	261:269	arg1	form					234:237	the most common form	218:237	the most common form of glomerulonephritis worldwide	218:269	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	1	7	theme	worldwide	261:269	arg1	defect					191:196	a heritable pathogenic defect	168:196	a heritable pathogenic defect in IgA nephropathy	168:215	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	7	8	from	secretion	1232:1240	arg1	cells					1271:1275	IgA1-producing cells	1256:1275	IgA1-producing cells	1256:1275	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	8	9	theme	IgA	1390:1392	arg1	nephropathy					1394:1404	IgA nephropathy	1390:1404	IgA nephropathy	1390:1404	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	5	10	theme	rs13226913	891:900	arg1	allele					881:886	the Gd-IgA1-increasing allele	858:886	the Gd-IgA1-increasing allele of rs13226913	858:900	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	5	10	theme	rs13226913	891:900	arg1	common					905:910	common	905:910	common	905:910	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	2	11	dep	=	606:606	arg1	rs5910940					593:601	rs5910940	593:601	rs5910940	593:601	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	2	12	theme	significant	519:529	arg1	loci					531:534	two genome-wide significant loci	503:534	two genome-wide significant loci	503:534	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	8	13	theme	other	1419:1423	arg1	traits					1433:1438	other complex traits	1419:1438	other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer	1419:1549	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	2	14	theme	genome-wide	507:517	arg1	loci					531:534	two genome-wide significant loci	503:534	two genome-wide significant loci	503:534	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	3	15	theme	enzymatic	673:681	arg1	O-glycosylation					683:697	enzymatic O-glycosylation	673:697	enzymatic O-glycosylation of IgA1	673:705	These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1.
28187132	2	16	dep	C1GALT1	540:546	arg1	rs13226913					549:558	rs13226913	549:558	rs13226913	549:558	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	6	17	theme	O-linked	1086:1093	arg1	glycans					1095:1101	O-linked glycans	1086:1101	O-linked glycans on IgA1	1086:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	5	18	from	rare	930:933	arg1	Asians					943:948	East Asians	938:948	East Asians	938:948	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	1	19	theme	heritable	170:178	arg1	defect					191:196	a heritable pathogenic defect	168:196	a heritable pathogenic defect in IgA nephropathy	168:215	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	1	19	theme	heritable	170:178	arg1	form					234:237	the most common form	218:237	the most common form of glomerulonephritis worldwide	218:269	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	1	20	gly	O-glycosylation	107:121	arg1	IgA1					151:154	serum immunoglobulin A1 (IgA1)	126:155	serum immunoglobulin A1 (IgA1)	126:155	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	2	21	dep	=	563:563	arg1	10-11					571:575	10-11	571:575	10-11	571:575	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	2	21	dep	=	563:563	arg1	3.2					565:567	3.2	565:567	3.2	565:567	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	5	22	from	Europeans	915:923	arg1	allele					881:886	the Gd-IgA1-increasing allele	858:886	the Gd-IgA1-increasing allele of rs13226913	858:900	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	5	22	from	Europeans	915:923	arg1	common					905:910	common	905:910	common	905:910	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	1	23	theme	pathogenic	180:189	arg1	defect					191:196	a heritable pathogenic defect	168:196	a heritable pathogenic defect in IgA nephropathy	168:215	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	1	23	theme	pathogenic	180:189	arg1	form					234:237	the most common form	218:237	the most common form of glomerulonephritis worldwide	218:269	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	2	24	dep	C1GALT1C1	582:590	arg1	=					606:606	=	606:606	=	606:606	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	3	25	gly	O-glycosylation	683:697	arg1	IgA1					702:705	IgA1	702:705	IgA1	702:705	These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1.
28187132	7	26	theme	siRNA	1124:1128	arg1	studies					1141:1147	in vitro siRNA knock-down studies	1115:1147	in vitro siRNA knock-down studies	1115:1147	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	3	27	theme	IgA1	702:705	arg1	O-glycosylation					683:697	enzymatic O-glycosylation	673:697	enzymatic O-glycosylation of IgA1	673:705	These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1.
28187132	6	28	theme	galactose	1073:1081	arg1	transfer					1061:1068	the transfer	1057:1068	the transfer of galactose to O-linked glycans on IgA1	1057:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	6	29	from	glycans	1095:1101	arg1	IgA1					1106:1109	IgA1	1106:1109	IgA1	1106:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	2	30	theme	serum	383:387	arg1	levels					389:394	serum levels	383:394	serum levels of galactose-deficient IgA1 (Gd-IgA1)	383:432	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	1	31	theme	specific	276:283	arg1	factors					293:299	specific genetic factors	276:299	specific genetic factors involved in its determination	276:329	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	2	32	from	GWAS	374:377	arg1	subjects					443:450	2,633 subjects	437:450	2,633 subjects of European and East Asian ancestry	437:486	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	1	33	theme	Aberrant	98:105	arg1	O-glycosylation					107:121	Aberrant O-glycosylation	98:121	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1)	98:155	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	5	34	from	Asians	943:948	arg1	rare					930:933	rare	930:933	rare	930:933	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	8	35	theme	O-glycosylation	1345:1359	arg1	regulation					1331:1340	the genetic regulation	1319:1340	the genetic regulation of O-glycosylation	1319:1359	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	0	36	theme	galactose-deficient	15:33	arg1	IgA1					35:38	serum galactose-deficient IgA1	9:38	serum galactose-deficient IgA1	9:38	GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway.
28187132	1	37	theme	genetic	285:291	arg1	factors					293:299	specific genetic factors	276:299	specific genetic factors involved in its determination	276:329	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	8	38	theme	novel	1299:1303	arg1	insights					1305:1312	novel insights	1299:1312	novel insights into the genetic regulation of O-glycosylation	1299:1359	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	1	39	theme	IgA	201:203	arg1	nephropathy					205:215	IgA nephropathy	201:215	IgA nephropathy	201:215	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	0	40	theme	serum	9:13	arg1	IgA1					35:38	serum galactose-deficient IgA1	9:38	serum galactose-deficient IgA1	9:38	GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway.
28187132	5	41	theme	Gd-IgA1-increasing	862:879	arg1	allele					881:886	the Gd-IgA1-increasing allele	858:886	the Gd-IgA1-increasing allele of rs13226913	858:900	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	5	41	theme	Gd-IgA1-increasing	862:879	arg1	common					905:910	common	905:910	common	905:910	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	7	42	from	cells	1271:1275	arg1	rate					1224:1227	the rate	1220:1227	the rate of secretion of Gd-IgA1 in IgA1-producing cells	1220:1275	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	6	43	theme	responsible	1041:1051	arg1	enzyme					1034:1039	the key enzyme	1026:1039	the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1	1026:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	6	43	theme	responsible	1041:1051	arg1	cis-eQTL					992:999	a strong cis-eQTL	983:999	a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1	983:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	7	44	theme	C1GALT1	1188:1194	arg1	levels					1173:1178	mRNA levels	1168:1178	mRNA levels of both C1GALT1 and C1GALT1C1	1168:1208	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	8	45	theme	hematologic	1519:1529	arg1	disease					1531:1537	hematologic disease	1519:1537	hematologic disease	1519:1537	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	2	46	theme	IgA1	419:422	arg1	levels					389:394	serum levels	383:394	serum levels of galactose-deficient IgA1 (Gd-IgA1)	383:432	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	6	47	theme	strong	985:990	arg1	enzyme					1034:1039	the key enzyme	1026:1039	the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1	1026:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	6	47	theme	strong	985:990	arg1	cis-eQTL					992:999	a strong cis-eQTL	983:999	a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1	983:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	5	48	theme	East	938:941	arg1	Asians					943:948	East Asians	938:948	East Asians	938:948	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	2	49	theme	galactose-deficient	399:417	arg1	IgA1					419:422	galactose-deficient IgA1	399:422	galactose-deficient IgA1 (Gd-IgA1)	399:432	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	2	49	theme	galactose-deficient	399:417	arg1	Gd-IgA1					425:431	Gd-IgA1	425:431	Gd-IgA1	425:431	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	2	50	theme	European	455:462	arg1	subjects					443:450	2,633 subjects	437:450	2,633 subjects of European and East Asian ancestry	437:486	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	8	51	theme	complex	1425:1431	arg1	traits					1433:1438	other complex traits	1419:1438	other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer	1419:1549	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	2	52	theme	=	563:563	arg1	P					561:561	P	561:561	P = 3.2 x 10-11	561:575	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	4	53	theme	variability	772:782	arg1	%					767:767	approximately 7%	752:767	approximately 7% of variability in circulating Gd-IgA1 in Europeans	752:818	We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians.
28187132	4	53	theme	variability	772:782	arg1	variability					772:782	variability	772:782	variability in circulating Gd-IgA1 in Europeans	772:818	We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians.
28187132	1	54	theme	serum	126:130	arg1	IgA1					151:154	serum immunoglobulin A1 (IgA1)	126:155	serum immunoglobulin A1 (IgA1)	126:155	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	0	55	theme	critical	51:58	arg1	genes					60:64	critical genes	51:64	critical genes of the O-glycosylation pathway	51:95	GWAS for serum galactose-deficient IgA1 implicates critical genes of the O-glycosylation pathway.
28187132	8	56	theme	bowel	1504:1508	arg1	disease					1510:1516	inflammatory bowel disease	1491:1516	inflammatory bowel disease	1491:1516	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	7	57	theme	mRNA	1168:1171	arg1	levels					1173:1178	mRNA levels	1168:1178	mRNA levels of both C1GALT1 and C1GALT1C1	1168:1208	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	8	58	theme	O-glycosylation	1456:1470	arg1	disease					1510:1516	inflammatory bowel disease	1491:1516	inflammatory bowel disease	1491:1516	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	8	58	theme	O-glycosylation	1456:1470	arg1	defects					1472:1478	O-glycosylation defects	1456:1478	O-glycosylation defects	1456:1478	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	8	58	theme	O-glycosylation	1456:1470	arg1	cancer					1544:1549	cancer	1544:1549	cancer	1544:1549	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	8	58	theme	O-glycosylation	1456:1470	arg1	disease					1531:1537	hematologic disease	1519:1537	hematologic disease	1519:1537	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	1	59	theme	immunoglobulin	132:145	arg1	IgA1					151:154	serum immunoglobulin A1 (IgA1)	126:155	serum immunoglobulin A1 (IgA1)	126:155	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	8	60	theme	inflammatory	1491:1502	arg1	disease					1510:1516	inflammatory bowel disease	1491:1516	inflammatory bowel disease	1491:1516	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	4	61	theme	East	836:839	arg1	Asians					841:846	East Asians	836:846	East Asians	836:846	We demonstrated that these two loci explain approximately 7% of variability in circulating Gd-IgA1 in Europeans, but only 2% in East Asians.
28187132	8	62	theme	genetic	1323:1329	arg1	regulation					1331:1340	the genetic regulation	1319:1340	the genetic regulation of O-glycosylation	1319:1359	Our findings provide novel insights into the genetic regulation of O-glycosylation and are relevant not only to IgA nephropathy, but also to other complex traits associated with O-glycosylation defects, including inflammatory bowel disease, hematologic disease, and cancer.
28187132	1	63	theme	A1	147:148	arg1	IgA1					151:154	serum immunoglobulin A1 (IgA1)	126:155	serum immunoglobulin A1 (IgA1)	126:155	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	6	64	link	O-linked	1086:1093	arg1	glycans					1095:1101	O-linked glycans	1086:1101	O-linked glycans on IgA1	1086:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	7	65	dep	in	1115:1116	arg1	vitro					1118:1122	vitro	1118:1122	vitro	1118:1122	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	2	66	from	loci	531:534	arg1	C1GALT1					540:546	C1GALT1	540:546	C1GALT1 (rs13226913, P = 3.2 x 10-11)	540:576	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	2	66	from	loci	531:534	arg1	C1GALT1C1					582:590	C1GALT1C1	582:590	C1GALT1C1 (rs5910940, P = 2.7 x 10-8)	582:618	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	7	67	theme	IgA1-producing	1256:1269	arg1	cells					1271:1275	IgA1-producing cells	1256:1275	IgA1-producing cells	1256:1275	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	1	68	from	defect	191:196	arg1	nephropathy					205:215	IgA nephropathy	201:215	IgA nephropathy	201:215	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	6	69	theme	key	1030:1032	arg1	enzyme					1034:1039	the key enzyme	1026:1039	the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1	1026:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	6	69	theme	key	1030:1032	arg1	cis-eQTL					992:999	a strong cis-eQTL	983:999	a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1	983:1109	Moreover, rs13226913 represents a strong cis-eQTL for C1GALT1 that encodes the key enzyme responsible for the transfer of galactose to O-linked glycans on IgA1.
28187132	1	70	theme	common	227:232	arg1	form					234:237	the most common form	218:237	the most common form of glomerulonephritis worldwide	218:269	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	1	70	theme	common	227:232	arg1	defect					191:196	a heritable pathogenic defect	168:196	a heritable pathogenic defect in IgA nephropathy	168:215	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	7	71	theme	knock-down	1130:1139	arg1	studies					1141:1147	in vitro siRNA knock-down studies	1115:1147	in vitro siRNA knock-down studies	1115:1147	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	7	72	theme	C1GALT1C1	1200:1208	arg1	levels					1173:1178	mRNA levels	1168:1178	mRNA levels of both C1GALT1 and C1GALT1C1	1168:1208	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	1	73	theme	IgA1	151:154	arg1	O-glycosylation					107:121	Aberrant O-glycosylation	98:121	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1)	98:155	Aberrant O-glycosylation of serum immunoglobulin A1 (IgA1) represents a heritable pathogenic defect in IgA nephropathy, the most common form of glomerulonephritis worldwide, but specific genetic factors involved in its determination are not known.
28187132	7	74	theme	secretion	1232:1240	arg1	rate					1224:1227	the rate	1220:1227	the rate of secretion of Gd-IgA1 in IgA1-producing cells	1220:1275	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	2	75	dep	rs13226913	549:558	arg1	P					561:561	P	561:561	P = 3.2 x 10-11	561:575	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	7	76	theme	Gd-IgA1	1245:1251	arg1	secretion					1232:1240	secretion	1232:1240	secretion of Gd-IgA1 in IgA1-producing cells	1232:1275	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
28187132	3	77	theme	molecular	640:648	arg1	genes					627:631	These genes	621:631	These genes	621:631	These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1.
28187132	3	77	theme	molecular	640:648	arg1	partners					650:657	molecular partners	640:657	molecular partners essential for enzymatic O-glycosylation of IgA1	640:705	These genes encode molecular partners essential for enzymatic O-glycosylation of IgA1.
28187132	2	78	theme	quantitative	361:372	arg1	GWAS					374:377	a quantitative GWAS	359:377	a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry	359:486	We performed a quantitative GWAS for serum levels of galactose-deficient IgA1 (Gd-IgA1) in 2,633 subjects of European and East Asian ancestry and discovered two genome-wide significant loci, in C1GALT1 (rs13226913, P = 3.2 x 10-11) and C1GALT1C1 (rs5910940, P = 2.7 x 10-8).
28187132	5	79	from	common	905:910	arg1	Europeans					915:923	Europeans	915:923	Europeans	915:923	Notably, the Gd-IgA1-increasing allele of rs13226913 is common in Europeans, but rare in East Asians.
28187132	7	80	theme	in	1115:1116	arg1	studies					1141:1147	in vitro siRNA knock-down studies	1115:1147	in vitro siRNA knock-down studies	1115:1147	By in vitro siRNA knock-down studies, we confirmed that mRNA levels of both C1GALT1 and C1GALT1C1 determine the rate of secretion of Gd-IgA1 in IgA1-producing cells.
31231989	1	0	theme	genes	234:238	arg1	variants					222:229	pathogenic variants	211:229	pathogenic variants of genes involved in protein or lipid glycosylation	211:281	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	7	1	theme	developmental	1074:1086	arg1	delay					1088:1092	severe developmental delay	1067:1092	severe developmental delay	1067:1092	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	6	2	theme	X-chromosome	860:871	arg1	pattern					886:892	The X-chromosome inactivation pattern	856:892	The X-chromosome inactivation pattern	856:892	The X-chromosome inactivation pattern was studied using the human androgen receptor assay.
31231989	4	3	theme	Whole-exome	632:642	arg1	sequencing					644:653	METHODS Whole-exome sequencing	624:653	METHODS Whole-exome sequencing	624:653	METHODS Whole-exome sequencing was performed on the patient's DNA, and candidate variants were confirmed by Sanger sequencing.
31231989	1	4	theme	glycosylation	159:171	arg1	diseases					192:199	genetic diseases	184:199	genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation	184:281	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	1	4	theme	glycosylation	159:171	arg1	CDGs					174:177	CDGs	174:177	CDGs	174:177	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	1	4	theme	glycosylation	159:171	arg1	disorders					146:154	BACKGROUND Congenital disorders	124:154	BACKGROUND Congenital disorders of glycosylation (CDGs)	124:178	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	2	5	with	CDGs	385:388	arg1	manner					416:421	an X-linked dominant manner	395:421	an X-linked dominant manner	395:421	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	3	6	theme	skeletal	550:557	arg1	features					559:566	abnormal facial and skeletal features	530:566	abnormal facial and skeletal features	530:566	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	3	7	theme	facial	539:544	arg1	features					559:566	abnormal facial and skeletal features	530:566	abnormal facial and skeletal features	530:566	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	7	8	from	myelination	1150:1160	arg1	MRI					1165:1167	MRI	1165:1167	MRI	1165:1167	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	7	9	from	variant	991:997	arg1	SLC35A2					1002:1008	SLC35A2	1002:1008	SLC35A2	1002:1008	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	0	10	theme	delayed	103:109	arg1	myelination					111:121	delayed myelination	103:121	delayed myelination	103:121	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	7	11	theme	cerebral	1120:1127	arg1	atrophy					1129:1135	mild cerebral atrophy	1115:1135	mild cerebral atrophy	1115:1135	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	5	12	theme	site	814:817	arg1	variant					819:825	the splice site variant	803:825	the splice site variant	803:825	cDNA analysis was performed to assess the effect of the splice site variant using peripheral leukocytes.
31231989	6	13	theme	androgen	922:929	arg1	assay					940:944	the human androgen receptor assay	912:944	the human androgen receptor assay	912:944	The X-chromosome inactivation pattern was studied using the human androgen receptor assay.
31231989	2	14	dep	De	284:285	arg1	novo					287:290	novo	287:290	novo	287:290	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	7	15	theme	splice	979:984	arg1	variant					991:997	a de novo splice site variant	969:997	a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A)	969:1034	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	8	16	theme	in-frame	1243:1250	arg1	insertion					1258:1266	an in-frame 33-bp insertion	1240:1266	an in-frame 33-bp insertion	1240:1266	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	7	17	theme	de	971:972	arg1	variant					991:997	a de novo splice site variant	969:997	a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A)	969:1034	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	3	18	theme	resonance	590:598	arg1	MRI					609:611	MRI	609:611	MRI	609:611	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	3	18	theme	resonance	590:598	arg1	imaging					600:606	magnetic resonance imaging	581:606	various magnetic resonance imaging (MRI) findings	573:621	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	1	19	theme	BACKGROUND	124:133	arg1	diseases					192:199	genetic diseases	184:199	genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation	184:281	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	1	19	theme	BACKGROUND	124:133	arg1	CDGs					174:177	CDGs	174:177	CDGs	174:177	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	1	19	theme	BACKGROUND	124:133	arg1	disorders					146:154	BACKGROUND Congenital disorders	124:154	BACKGROUND Congenital disorders of glycosylation (CDGs)	124:178	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	7	20	from	paraplegia	1103:1112	arg1	MRI					1165:1167	MRI	1165:1167	MRI	1165:1167	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	10	21	theme	galactose	1397:1405	arg1	loss					1389:1392	Partial loss	1381:1392	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin	1381:1466	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	2	22	from	variants	292:299	arg1	gene					316:319	the SLC35A2 gene	304:319	the SLC35A2 gene	304:319	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	2	22	from	variants	292:299	arg1	transporter					352:362	a UDP-galactose transporter	336:362	a UDP-galactose transporter	336:362	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	4	23	theme	Sanger	732:737	arg1	sequencing					739:748	Sanger sequencing	732:748	Sanger sequencing	732:748	METHODS Whole-exome sequencing was performed on the patient's DNA, and candidate variants were confirmed by Sanger sequencing.
31231989	7	24	from	atrophy	1129:1135	arg1	MRI					1165:1167	MRI	1165:1167	MRI	1165:1167	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	8	25	theme	acid	1294:1297	arg1	insertion					1299:1307	an 11-amino acid insertion	1282:1307	an 11-amino acid insertion in the presumptive cytoplasmic loop	1282:1343	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	0	26	theme	spastic	79:85	arg1	paraplegia					87:96	spastic paraplegia	79:96	spastic paraplegia	79:96	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	0	27	theme	splice	18:23	arg1	variant					30:36	de novo splice site variant	10:36	de novo splice site variant	10:36	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	10	28	theme	sialic	1411:1416	arg1	acid					1418:1421	sialic acid	1411:1421	sialic acid	1411:1421	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	11	29	dep	spasticity	1597:1606	arg1	seizures					1615:1622	seizures	1615:1622	seizures	1615:1622	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	2	30	theme	X-linked	398:405	arg1	manner					416:421	an X-linked dominant manner	395:421	an X-linked dominant manner	395:421	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	8	31	theme	presumptive	1316:1326	arg1	loop					1340:1343	the presumptive cytoplasmic loop	1312:1343	the presumptive cytoplasmic loop	1312:1343	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	1	32	theme	lipid	263:267	arg1	glycosylation					269:281	lipid glycosylation	263:281	lipid glycosylation	263:281	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	10	33	theme	N-linked	1430:1437	arg1	glycans					1439:1445	the N-linked glycans	1426:1445	the N-linked glycans of serum transferrin	1426:1466	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	7	34	theme	mild	1115:1118	arg1	atrophy					1129:1135	mild cerebral atrophy	1115:1135	mild cerebral atrophy	1115:1135	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	11	35	theme	disorders	1559:1567	arg1	spectrum					1531:1538	the phenotypic spectrum	1516:1538	the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures	1516:1622	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	0	36	theme	site	25:28	arg1	variant					30:36	de novo splice site variant	10:36	de novo splice site variant	10:36	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	10	37	theme	transferrin	1456:1466	arg1	glycans					1439:1445	the N-linked glycans	1426:1445	the N-linked glycans of serum transferrin	1426:1466	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	3	38	theme	psychomotor	486:496	arg1	delay					512:516	psychomotor developmental delay	486:516	psychomotor developmental delay	486:516	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	1	39	theme	pathogenic	211:220	arg1	variants					222:229	pathogenic variants	211:229	pathogenic variants of genes involved in protein or lipid glycosylation	211:281	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	7	40	theme	spastic	1095:1101	arg1	paraplegia					1103:1112	spastic paraplegia	1095:1112	spastic paraplegia	1095:1112	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	11	41	theme	delayed	1572:1578	arg1	myelination					1580:1590	delayed myelination	1572:1590	delayed myelination with spasticity and no seizures	1572:1622	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	7	42	theme	severe	1067:1072	arg1	delay					1088:1092	severe developmental delay	1067:1092	severe developmental delay	1067:1092	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	8	43	from	insertion	1299:1307	arg1	loop					1340:1343	the presumptive cytoplasmic loop	1312:1343	the presumptive cytoplasmic loop	1312:1343	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	6	44	theme	inactivation	873:884	arg1	pattern					886:892	The X-chromosome inactivation pattern	856:892	The X-chromosome inactivation pattern	856:892	The X-chromosome inactivation pattern was studied using the human androgen receptor assay.
31231989	5	45	theme	variant	819:825	arg1	effect					793:798	the effect	789:798	the effect of the splice site variant	789:825	cDNA analysis was performed to assess the effect of the splice site variant using peripheral leukocytes.
31231989	4	46	theme	METHODS	624:630	arg1	sequencing					644:653	METHODS Whole-exome sequencing	624:653	METHODS Whole-exome sequencing	624:653	METHODS Whole-exome sequencing was performed on the patient's DNA, and candidate variants were confirmed by Sanger sequencing.
31231989	7	47	theme	female	1041:1046	arg1	patient					1048:1054	a female patient	1039:1054	a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures	1039:1184	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	11	48	theme	phenotypic	1520:1529	arg1	spectrum					1531:1538	the phenotypic spectrum	1516:1538	the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures	1516:1622	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	5	49	theme	peripheral	833:842	arg1	leukocytes					844:853	peripheral leukocytes	833:853	peripheral leukocytes	833:853	cDNA analysis was performed to assess the effect of the splice site variant using peripheral leukocytes.
31231989	2	50	theme	De	284:285	arg1	variants					292:299	De novo variants	284:299	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter,	284:363	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	5	51	theme	splice	807:812	arg1	variant					819:825	the splice site variant	803:825	the splice site variant	803:825	cDNA analysis was performed to assess the effect of the splice site variant using peripheral leukocytes.
31231989	6	52	theme	receptor	931:938	arg1	assay					940:944	the human androgen receptor assay	912:944	the human androgen receptor assay	912:944	The X-chromosome inactivation pattern was studied using the human androgen receptor assay.
31231989	8	53	theme	aberrant	1209:1216	arg1	splicing					1218:1225	an aberrant splicing	1206:1225	an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop	1206:1343	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	6	54	theme	human	916:920	arg1	assay					940:944	the human androgen receptor assay	912:944	the human androgen receptor assay	912:944	The X-chromosome inactivation pattern was studied using the human androgen receptor assay.
31231989	3	55	theme	imaging	600:606	arg1	findings					614:621	various magnetic resonance imaging (MRI) findings	573:621	various magnetic resonance imaging (MRI) findings	573:621	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	7	56	theme	site	986:989	arg1	variant					991:997	a de novo splice site variant	969:997	a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A)	969:1034	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	3	57	theme	abnormal	530:537	arg1	features					559:566	abnormal facial and skeletal features	530:566	abnormal facial and skeletal features	530:566	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	7	58	dep	RESULTS	947:953	arg1	identified					958:967	identified	958:967	identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures	958:1184	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	3	59	theme	magnetic	581:588	arg1	MRI					609:611	MRI	609:611	MRI	609:611	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	3	59	theme	magnetic	581:588	arg1	imaging					600:606	magnetic resonance imaging	581:606	various magnetic resonance imaging (MRI) findings	573:621	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	8	60	theme	33-bp	1252:1256	arg1	insertion					1258:1266	an in-frame 33-bp insertion	1240:1266	an in-frame 33-bp insertion	1240:1266	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	0	61	theme	developmental	57:69	arg1	delays					71:76	developmental delays	57:76	developmental delays	57:76	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	1	62	theme	Congenital	135:144	arg1	diseases					192:199	genetic diseases	184:199	genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation	184:281	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	1	62	theme	Congenital	135:144	arg1	CDGs					174:177	CDGs	174:177	CDGs	174:177	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	1	62	theme	Congenital	135:144	arg1	disorders					146:154	BACKGROUND Congenital disorders	124:154	BACKGROUND Congenital disorders of glycosylation (CDGs)	124:178	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	0	63	from	case	2:5	arg1	SLC35A2					41:47	SLC35A2	41:47	SLC35A2	41:47	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	2	64	link	X-linked	398:405	arg1	manner					416:421	an X-linked dominant manner	395:421	an X-linked dominant manner	395:421	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	10	65	theme	Partial	1381:1387	arg1	loss					1389:1392	Partial loss	1381:1392	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin	1381:1466	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	10	66	link	N-linked	1430:1437	arg1	glycans					1439:1445	the N-linked glycans	1426:1445	the N-linked glycans of serum transferrin	1426:1466	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	7	67	theme	delayed	1142:1148	arg1	myelination					1150:1160	delayed myelination	1142:1160	delayed myelination	1142:1160	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	10	68	theme	acid	1418:1421	arg1	loss					1389:1392	Partial loss	1381:1392	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin	1381:1466	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	8	69	theme	11-amino	1285:1292	arg1	insertion					1299:1307	an 11-amino acid insertion	1282:1307	an 11-amino acid insertion in the presumptive cytoplasmic loop	1282:1343	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	2	70	theme	dominant	407:414	arg1	manner					416:421	an X-linked dominant manner	395:421	an X-linked dominant manner	395:421	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	4	71	theme	candidate	695:703	arg1	variants					705:712	candidate variants	695:712	candidate variants	695:712	METHODS Whole-exome sequencing was performed on the patient's DNA, and candidate variants were confirmed by Sanger sequencing.
31231989	2	72	theme	UDP-galactose	338:350	arg1	gene					316:319	the SLC35A2 gene	304:319	the SLC35A2 gene	304:319	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	2	72	theme	UDP-galactose	338:350	arg1	transporter					352:362	a UDP-galactose transporter	336:362	a UDP-galactose transporter	336:362	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	0	73	theme	de	10:11	arg1	variant					30:36	de novo splice site variant	10:36	de novo splice site variant	10:36	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	10	74	theme	glycans	1439:1445	arg1	galactose					1397:1405	galactose	1397:1405	galactose	1397:1405	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	10	74	theme	glycans	1439:1445	arg1	acid					1418:1421	sialic acid	1411:1421	sialic acid	1411:1421	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	7	75	dep	de	971:972	arg1	novo					974:977	novo	974:977	novo	974:977	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	3	76	theme	related	440:446	arg1	symptoms					431:438	Common symptoms	424:438	Common symptoms related to SLC35A2 variants	424:466	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	5	77	theme	cDNA	751:754	arg1	analysis					756:763	cDNA analysis	751:763	cDNA analysis	751:763	cDNA analysis was performed to assess the effect of the splice site variant using peripheral leukocytes.
31231989	1	78	theme	genetic	184:190	arg1	disorders					146:154	BACKGROUND Congenital disorders	124:154	BACKGROUND Congenital disorders of glycosylation (CDGs)	124:178	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	1	78	theme	genetic	184:190	arg1	diseases					192:199	genetic diseases	184:199	genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation	184:281	BACKGROUND Congenital disorders of glycosylation (CDGs) are genetic diseases caused by pathogenic variants of genes involved in protein or lipid glycosylation.
31231989	8	79	theme	cytoplasmic	1328:1338	arg1	loop					1340:1343	the presumptive cytoplasmic loop	1312:1343	the presumptive cytoplasmic loop	1312:1343	The variant led to an aberrant splicing resulting in an in-frame 33-bp insertion, which caused an 11-amino acid insertion in the presumptive cytoplasmic loop.
31231989	11	80	theme	SLC35A2-related	1543:1557	arg1	disorders					1559:1567	SLC35A2-related disorders	1543:1567	SLC35A2-related disorders	1543:1567	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	3	81	theme	Common	424:429	arg1	symptoms					431:438	Common symptoms	424:438	Common symptoms related to SLC35A2 variants	424:466	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	0	82	theme	variant	30:36	arg1	case					2:5	A case	0:5	A case of de novo splice site variant in SLC35A2	0:47	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	7	83	from	delay	1088:1092	arg1	MRI					1165:1167	MRI	1165:1167	MRI	1165:1167	RESULTS We identified a de novo splice site variant in SLC35A2 (NM_005660.2: c.274+1G>A) in a female patient who showed severe developmental delay, spastic paraplegia, mild cerebral atrophy, and delayed myelination on MRI, but no seizures.
31231989	2	84	theme	SLC35A2	308:314	arg1	gene					316:319	the SLC35A2 gene	304:319	the SLC35A2 gene	304:319	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	2	84	theme	SLC35A2	308:314	arg1	transporter					352:362	a UDP-galactose transporter	336:362	a UDP-galactose transporter	336:362	De novo variants in the SLC35A2 gene, which encodes a UDP-galactose transporter, are responsible for CDGs with an X-linked dominant manner.
31231989	0	85	dep	de	10:11	arg1	novo					13:16	novo	13:16	novo	13:16	A case of de novo splice site variant in SLC35A2 showing developmental delays, spastic paraplegia, and delayed myelination.
31231989	3	86	theme	various	573:579	arg1	findings					614:621	various magnetic resonance imaging (MRI) findings	573:621	various magnetic resonance imaging (MRI) findings	573:621	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	11	87	dep	CONCLUSION	1482:1491	arg1	expand					1509:1514	expand	1509:1514	would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures	1503:1622	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	10	88	theme	serum	1450:1454	arg1	transferrin					1456:1466	serum transferrin	1450:1466	serum transferrin	1450:1466	Partial loss of galactose and sialic acid of the N-linked glycans of serum transferrin was observed.
31231989	3	89	theme	SLC35A2	451:457	arg1	variants					459:466	SLC35A2 variants	451:466	SLC35A2 variants	451:466	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	11	90	with	myelination	1580:1590	arg1	no					1612:1613	no	1612:1613	no	1612:1613	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	11	90	with	myelination	1580:1590	arg1	spasticity					1597:1606	spasticity	1597:1606	spasticity	1597:1606	CONCLUSION This case would expand the phenotypic spectrum of SLC35A2-related disorders to delayed myelination with spasticity and no seizures.
31231989	3	91	theme	developmental	498:510	arg1	delay					512:516	psychomotor developmental delay	486:516	psychomotor developmental delay	486:516	Common symptoms related to SLC35A2 variants include epilepsy, psychomotor developmental delay, hypotonia, abnormal facial and skeletal features, and various magnetic resonance imaging (MRI) findings.
31231989	9	92	theme	X-inactivation	1346:1359	arg1	pattern					1361:1367	X-inactivation pattern	1346:1367	X-inactivation pattern	1346:1367	X-inactivation pattern was random.
30913278	0	0	theme	T-helper	100:107	arg1	responses					122:130	T-helper 1 (TH1)/TH17 responses	100:130	T-helper 1 (TH1)/TH17 responses	100:130	Increasing cell permeability of N-acetylglucosamine via 6-acetylation enhances capacity to suppress T-helper 1 (TH1)/TH17 responses and autoimmunity.
30913278	2	1	theme	Golgi	472:476	arg1	enzymes					488:494	the Golgi branching enzymes	468:494	the Golgi branching enzymes	468:494	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	4	2	theme	UDP-GlcNAc	705:714	arg1	synthesis					716:724	de novo UDP-GlcNAc synthesis	697:724	de novo UDP-GlcNAc synthesis	697:724	This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching.
30913278	2	3	theme	N-glycan	345:352	arg1	branching					354:362	N-glycan branching	345:362	N-glycan branching in T cells	345:373	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	5	4	theme	GlcNAc	761:766	arg1	Salvage					750:756	Salvage	750:756	Salvage of GlcNAc into the hexosamine pathway	750:794	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	1	5	theme	cell	243:246	arg1	responses					248:256	pro-inflammatory T cell responses	224:256	pro-inflammatory T cell responses	224:256	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	8	6	theme	cytoplasmic	1348:1358	arg1	esterases					1360:1368	cytoplasmic esterases	1348:1368	cytoplasmic esterases allowing salvage into the hexosamine pathway	1348:1413	Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway.
30913278	10	7	theme	Autoimmune	1734:1743	arg1	model					1778:1782	a mouse model	1770:1782	a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS	1770:1969	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	10	7	theme	Autoimmune	1734:1743	arg1	EAE					1764:1766	EAE	1764:1766	EAE	1764:1766	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	10	7	theme	Autoimmune	1734:1743	arg1	Encephalomyelitis					1745:1761	Experimental Autoimmune Encephalomyelitis	1721:1761	Experimental Autoimmune Encephalomyelitis (EAE)	1721:1767	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	1	8	link	-linked	199:205	arg1	glycans					207:213	Asn (N)-linked glycans	192:213	Asn (N)-linked glycans	192:213	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	3	9	theme	Activated	497:505	arg1	cells					509:513	Activated T cells	497:513	Activated T cells	497:513	Activated T cells switch metabolism from oxidative phosphorylation to aerobic glycolysis and glutaminolysis.
30913278	10	10	theme	mouse	1772:1776	arg1	model					1778:1782	a mouse model	1770:1782	a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS	1770:1969	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	10	10	theme	mouse	1772:1776	arg1	Encephalomyelitis					1745:1761	Experimental Autoimmune Encephalomyelitis	1721:1761	Experimental Autoimmune Encephalomyelitis (EAE)	1721:1767	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	7	11	theme	superior	1215:1222	arg1	form					1233:1236	a superior pro-drug form	1213:1236	a superior pro-drug form of GlcNAc	1213:1246	Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc.
30913278	7	11	theme	superior	1215:1222	arg1	GlcNAc-6-acetate					1193:1208	GlcNAc-6-acetate	1193:1208	GlcNAc-6-acetate	1193:1208	Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc.
30913278	5	12	theme	metabolic	811:819	arg1	suppression					821:831	this metabolic suppression	806:831	this metabolic suppression	806:831	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	9	13	theme	significant	1593:1603	arg1	toxicity					1605:1612	significant toxicity	1593:1612	significant toxicity	1593:1612	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	9	14	theme	T	1469:1469	arg1	cells					1471:1475	T cells	1469:1475	T cells	1469:1475	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	7	15	theme	pro-drug	1224:1231	arg1	form					1233:1236	a superior pro-drug form	1213:1236	a superior pro-drug form of GlcNAc	1213:1246	Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc.
30913278	7	15	theme	pro-drug	1224:1231	arg1	GlcNAc-6-acetate					1193:1208	GlcNAc-6-acetate	1193:1208	GlcNAc-6-acetate	1193:1208	Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc.
30913278	4	16	theme	de	697:698	arg1	synthesis					716:724	de novo UDP-GlcNAc synthesis	697:724	de novo UDP-GlcNAc synthesis	697:724	This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching.
30913278	3	17	theme	oxidative	538:546	arg1	phosphorylation					548:562	oxidative phosphorylation	538:562	oxidative phosphorylation	538:562	Activated T cells switch metabolism from oxidative phosphorylation to aerobic glycolysis and glutaminolysis.
30913278	8	18	theme	membrane	1291:1298	arg1	permeability					1300:1311	cell membrane permeability	1286:1311	cell membrane permeability	1286:1311	Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway.
30913278	10	19	theme	TH1/TH17	1675:1682	arg1	responses					1684:1692	TH1/TH17 responses	1675:1692	TH1/TH17 responses	1675:1692	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	5	20	theme	N-glycan	869:876	arg1	branching					878:886	N-glycan branching	869:886	N-glycan branching	869:886	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	4	21	dep	de	697:698	arg1	novo					700:703	novo	700:703	novo	700:703	This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching.
30913278	10	22	theme	Experimental	1721:1732	arg1	model					1778:1782	a mouse model	1770:1782	a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS	1770:1969	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	10	22	theme	Experimental	1721:1732	arg1	EAE					1764:1766	EAE	1764:1766	EAE	1764:1766	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	10	22	theme	Experimental	1721:1732	arg1	Encephalomyelitis					1745:1761	Experimental Autoimmune Encephalomyelitis	1721:1761	Experimental Autoimmune Encephalomyelitis (EAE)	1721:1767	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	6	23	theme	surface	1092:1098	arg1	transporter					1100:1110	a cell surface transporter	1085:1110	a cell surface transporter	1085:1110	However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis.
30913278	0	24	theme	TH1	112:114	arg1	responses					122:130	T-helper 1 (TH1)/TH17 responses	100:130	T-helper 1 (TH1)/TH17 responses	100:130	Increasing cell permeability of N-acetylglucosamine via 6-acetylation enhances capacity to suppress T-helper 1 (TH1)/TH17 responses and autoimmunity.
30913278	8	25	theme	hexosamine	1396:1405	arg1	pathway					1407:1413	the hexosamine pathway	1392:1413	the hexosamine pathway	1392:1413	Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway.
30913278	4	26	theme	hexosamine	658:667	arg1	pathway					669:675	the hexosamine pathway	654:675	the hexosamine pathway	654:675	This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching.
30913278	0	27	theme	cell	11:14	arg1	permeability					16:27	cell permeability	11:27	cell permeability of N-acetylglucosamine	11:50	Increasing cell permeability of N-acetylglucosamine via 6-acetylation enhances capacity to suppress T-helper 1 (TH1)/TH17 responses and autoimmunity.
30913278	3	28	theme	aerobic	567:573	arg1	glycolysis					575:584	aerobic glycolysis	567:584	aerobic glycolysis	567:584	Activated T cells switch metabolism from oxidative phosphorylation to aerobic glycolysis and glutaminolysis.
30913278	5	29	theme	anti-inflammatory	907:923	arg1	Treg					939:942	Treg	939:942	Treg	939:942	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	5	29	theme	anti-inflammatory	907:923	arg1	T					925:925	anti-inflammatory T regulatory	907:936	anti-inflammatory T regulatory (Treg)	907:943	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	2	30	theme	UDP-GlcNAc	432:441	arg1	biosynthesis					416:427	de novo hexosamine pathway biosynthesis	389:427	de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes	389:494	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	10	31	theme	pro-inflammatory	1896:1911	arg1	responses					1920:1928	pro-inflammatory T cell responses	1896:1928	pro-inflammatory T cell responses	1896:1928	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	8	32	theme	cell	1286:1289	arg1	permeability					1300:1311	cell membrane permeability	1286:1311	cell membrane permeability	1286:1311	Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway.
30913278	2	33	theme	T	367:367	arg1	cells					369:373	T cells	367:373	T cells	367:373	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	5	34	theme	UDP-GlcNAc	844:853	arg1	synthesis					855:863	UDP-GlcNAc synthesis	844:863	UDP-GlcNAc synthesis	844:863	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	1	35	theme	autoimmune	272:281	arg1	diseases					283:290	autoimmune diseases	272:290	autoimmune diseases such as Multiple Sclerosis (MS)	272:322	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	1	35	theme	autoimmune	272:281	arg1	Sclerosis					309:317	Multiple Sclerosis	300:317	Multiple Sclerosis (MS)	300:322	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	2	36	from	branching	354:362	arg1	cells					369:373	T cells	367:373	T cells	367:373	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	5	37	theme	hexosamine	777:786	arg1	pathway					788:794	the hexosamine pathway	773:794	the hexosamine pathway	773:794	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	2	38	theme	pathway	408:414	arg1	biosynthesis					416:427	de novo hexosamine pathway biosynthesis	389:427	de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes	389:494	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	10	39	theme	cell	1644:1647	arg1	activation/proliferation					1649:1672	T cell activation/proliferation	1642:1672	T cell activation/proliferation	1642:1672	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	1	40	theme	diseases	283:290	arg1	responses					248:256	pro-inflammatory T cell responses	224:256	pro-inflammatory T cell responses	224:256	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	1	40	theme	diseases	283:290	arg1	models					262:267	models	262:267	models of autoimmune diseases such as Multiple Sclerosis (MS)	262:322	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	6	41	theme	GlcNAc	1043:1048	arg1	activity					1050:1057	GlcNAc activity	1043:1057	GlcNAc activity	1043:1057	However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis.
30913278	6	42	theme	transporter	1100:1110	arg1	lack					1077:1080	the lack	1073:1080	the lack of a cell surface transporter	1073:1110	However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis.
30913278	5	43	theme	regulatory	927:936	arg1	Treg					939:942	Treg	939:942	Treg	939:942	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	5	43	theme	regulatory	927:936	arg1	T					925:925	anti-inflammatory T regulatory	907:936	anti-inflammatory T regulatory (Treg)	907:943	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	2	44	theme	hexosamine	397:406	arg1	biosynthesis					416:427	de novo hexosamine pathway biosynthesis	389:427	de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes	389:494	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	9	45	from	toxicity	1457:1464	arg1	cells					1471:1475	T cells	1469:1475	T cells	1469:1475	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	10	46	theme	autoimmune	1940:1949	arg1	diseases					1951:1958	autoimmune diseases	1940:1958	autoimmune diseases such as MS	1940:1969	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	10	46	theme	autoimmune	1940:1949	arg1	MS					1968:1969	MS	1968:1969	MS	1968:1969	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	8	47	theme	amino-sugars	1264:1275	arg1	Acetylation					1249:1259	Acetylation	1249:1259	Acetylation of amino-sugars	1249:1275	Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway.
30913278	0	48	theme	N-acetylglucosamine	32:50	arg1	permeability					16:27	cell permeability	11:27	cell permeability of N-acetylglucosamine	11:50	Increasing cell permeability of N-acetylglucosamine via 6-acetylation enhances capacity to suppress T-helper 1 (TH1)/TH17 responses and autoimmunity.
30913278	10	49	theme	disease	1698:1704	arg1	progression					1706:1716	disease progression	1698:1716	disease progression	1698:1716	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	9	50	theme	>	1517:1517	arg1	position					1521:1528	only the 6 > 3 position	1506:1528	only the 6 > 3 position	1506:1528	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	2	51	dep	de	389:390	arg1	novo					392:395	novo	392:395	novo	392:395	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	1	52	theme	-linked	199:205	arg1	glycans					207:213	Asn (N)-linked glycans	192:213	Asn (N)-linked glycans	192:213	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	2	53	theme	donor	448:452	arg1	UDP-GlcNAc					432:441	UDP-GlcNAc	432:441	UDP-GlcNAc	432:441	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	2	53	theme	donor	448:452	arg1	substrate					454:462	the donor substrate	444:462	the donor substrate for the Golgi branching enzymes	444:494	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	1	54	theme	Multiple	300:307	arg1	MS					320:321	MS	320:321	MS	320:321	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	1	54	theme	Multiple	300:307	arg1	Sclerosis					309:317	Multiple Sclerosis	300:317	Multiple Sclerosis (MS)	300:322	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	10	55	theme	T	1642:1642	arg1	activation/proliferation					1649:1672	T cell activation/proliferation	1642:1672	T cell activation/proliferation	1642:1672	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	5	56	theme	TH1	988:990	arg1	differentiation					992:1006	TH1 differentiation	988:1006	TH1 differentiation	988:1006	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	6	57	theme	high	1125:1128	arg1	doses					1130:1134	high doses	1125:1134	high doses	1125:1134	However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis.
30913278	8	58	theme	subsequent	1319:1328	arg1	de-acetylation					1330:1343	subsequent de-acetylation	1319:1343	subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway	1319:1413	Acetylation of amino-sugars improves cell membrane permeability, with subsequent de-acetylation by cytoplasmic esterases allowing salvage into the hexosamine pathway.
30913278	9	59	theme	N-glycan	1537:1544	arg1	branching					1546:1554	N-glycan branching	1537:1554	N-glycan branching	1537:1554	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	10	60	theme	N-glycan	1868:1875	arg1	branching					1877:1885	N-glycan branching	1868:1885	N-glycan branching	1868:1885	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	5	61	theme	pro-inflammatory	950:965	arg1	TH					977:978	TH	977:978	TH	977:978	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	5	61	theme	pro-inflammatory	950:965	arg1	helper					969:974	pro-inflammatory T helper	950:974	pro-inflammatory T helper (TH) 17	950:982	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	10	62	theme	therapeutic	1838:1848	arg1	approach					1850:1857	an improved therapeutic approach	1826:1857	an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS	1826:1969	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	9	63	from	position	1521:1528	arg1	mono-acetylation					1486:1501	mono-acetylation	1486:1501	mono-acetylation at only the 6 > 3 position	1486:1528	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	10	64	theme	improved	1829:1836	arg1	approach					1850:1857	an improved therapeutic approach	1826:1857	an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS	1826:1969	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	5	65	theme	T	967:967	arg1	TH					977:978	TH	977:978	TH	977:978	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	5	65	theme	T	967:967	arg1	helper					969:974	pro-inflammatory T helper	950:974	pro-inflammatory T helper (TH) 17	950:982	Salvage of GlcNAc into the hexosamine pathway overcomes this metabolic suppression to restore UDP-GlcNAc synthesis and N-glycan branching, thereby promoting anti-inflammatory T regulatory (Treg) over pro-inflammatory T helper (TH) 17 and TH1 differentiation to suppress autoimmunity.
30913278	1	66	theme	glycans	207:213	arg1	branching					179:187	N-acetylglucosamine (GlcNAc) branching	150:187	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans	150:213	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	10	67	theme	cell	1915:1918	arg1	responses					1920:1928	pro-inflammatory T cell responses	1896:1928	pro-inflammatory T cell responses	1896:1928	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	4	68	theme	N-glycan	730:737	arg1	branching					739:747	N-glycan branching	730:747	N-glycan branching	730:747	This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching.
30913278	9	69	theme	GlcNAc	1443:1448	arg1	Per-					1416:1419	Per-	1416:1419	Per-	1416:1419	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	9	69	theme	GlcNAc	1443:1448	arg1	bi-acetylation					1425:1438	bi-acetylation	1425:1438	bi-acetylation	1425:1438	Per- and bi-acetylation of GlcNAc led to toxicity in T cells, whereas mono-acetylation at only the 6 > 3 position raised N-glycan branching greater than GlcNAc without inducing significant toxicity.
30913278	7	70	theme	GlcNAc	1241:1246	arg1	form					1233:1236	a superior pro-drug form	1213:1236	a superior pro-drug form of GlcNAc	1213:1246	Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc.
30913278	7	70	theme	GlcNAc	1241:1246	arg1	GlcNAc-6-acetate					1193:1208	GlcNAc-6-acetate	1193:1208	GlcNAc-6-acetate	1193:1208	Here we report that GlcNAc-6-acetate is a superior pro-drug form of GlcNAc.
30913278	2	71	theme	de	389:390	arg1	biosynthesis					416:427	de novo hexosamine pathway biosynthesis	389:427	de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes	389:494	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	10	72	theme	T	1913:1913	arg1	responses					1920:1928	pro-inflammatory T cell responses	1896:1928	pro-inflammatory T cell responses	1896:1928	GlcNAc-6-acetate inhibited T cell activation/proliferation, TH1/TH17 responses and disease progression in Experimental Autoimmune Encephalomyelitis (EAE), a mouse model of MS. Thus, GlcNAc-6-Acetate may provide an improved therapeutic approach to raise N-glycan branching, inhibit pro-inflammatory T cell responses and treat autoimmune diseases such as MS.
30913278	4	73	theme	glucose	627:633	arg1	flux					619:622	flux	619:622	flux of glucose and glutamine into the hexosamine pathway	619:675	This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching.
30913278	3	74	theme	T	507:507	arg1	cells					509:513	Activated T cells	497:513	Activated T cells	497:513	Activated T cells switch metabolism from oxidative phosphorylation to aerobic glycolysis and glutaminolysis.
30913278	6	75	theme	cell	1087:1090	arg1	transporter					1100:1110	a cell surface transporter	1085:1110	a cell surface transporter	1085:1110	However, GlcNAc activity is limited by the lack of a cell surface transporter and requires high doses to enter cells via macropinocytosis.
30913278	1	76	theme	pro-inflammatory	224:239	arg1	responses					248:256	pro-inflammatory T cell responses	224:256	pro-inflammatory T cell responses	224:256	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	2	77	theme	branching	478:486	arg1	enzymes					488:494	the Golgi branching enzymes	468:494	the Golgi branching enzymes	468:494	Metabolism controls N-glycan branching in T cells by regulating de novo hexosamine pathway biosynthesis of UDP-GlcNAc, the donor substrate for the Golgi branching enzymes.
30913278	4	78	theme	glutamine	639:647	arg1	flux					619:622	flux	619:622	flux of glucose and glutamine into the hexosamine pathway	619:675	This reduces flux of glucose and glutamine into the hexosamine pathway, thereby inhibiting de novo UDP-GlcNAc synthesis and N-glycan branching.
30913278	1	79	theme	N-acetylglucosamine	150:168	arg1	branching					179:187	N-acetylglucosamine (GlcNAc) branching	150:187	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans	150:213	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30913278	1	80	theme	T	241:241	arg1	responses					248:256	pro-inflammatory T cell responses	224:256	pro-inflammatory T cell responses	224:256	N-acetylglucosamine (GlcNAc) branching of Asn (N)-linked glycans inhibits pro-inflammatory T cell responses and models of autoimmune diseases such as Multiple Sclerosis (MS).
30684504	8	0	theme	abnormal	1731:1738	arg1	signs					1754:1758	no abnormal toxicological signs	1728:1758	no abnormal toxicological signs	1728:1758	Finally, a four-week repeated dose toxicity study revealed no abnormal toxicological signs.
30684504	3	1	theme	CHO-S	911:915	arg1	cells					918:922	Chinese hamster ovary-S (CHO-S) cells	886:922	Chinese hamster ovary-S (CHO-S) cells	886:922	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	4	2	theme	glycosylated	941:952	arg1	form					954:957	its N-linked glycosylated form	928:957	its N-linked glycosylated form	928:957	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	0	3	theme	interferon-β	170:181	arg1	fusion					111:116	genetic fusion	103:116	genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β	103:181	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	1	4	theme	long-acting	398:408	arg1	Plegridy					421:428	Plegridy	421:428	Plegridy	421:428	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	4	theme	long-acting	398:408	arg1	rIFN-β-1a					410:418	long-acting rIFN-β-1a	398:418	long-acting rIFN-β-1a (Plegridy)	398:429	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	2	5	theme	extended	562:569	arg1	half-life					577:585	an extended serum half-life	559:585	an extended serum half-life	559:585	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	3	6	theme	ovary-S	902:908	arg1	cells					918:922	Chinese hamster ovary-S (CHO-S) cells	886:922	Chinese hamster ovary-S (CHO-S) cells	886:922	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	4	7	theme	culture	1018:1024	arg1	supernatant					1026:1036	the culture supernatant	1014:1036	the culture supernatant	1014:1036	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	4	8	link	N-linked	932:939	arg1	form					954:957	its N-linked glycosylated form	928:957	its N-linked glycosylated form	928:957	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	3	9	theme	long-acting	670:680	arg1	rIFN-®					682:687	a long-acting rIFN-®	668:687	a long-acting rIFN-®	668:687	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	0	10	theme	SL335	121:125	arg1	fusion					111:116	genetic fusion	103:116	genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β	103:181	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	1	11	theme	long-acting	330:340	arg1	rIFN-β					342:347	a long-acting rIFN-β	328:347	a long-acting rIFN-β	328:347	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	6	12	theme	antiviral	1370:1378	arg1	potency					1380:1386	antiviral potency	1370:1386	antiviral potency	1370:1386	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	1	13	theme	human	196:200	arg1	treatment					262:270	a first-line treatment	249:270	a first-line treatment for multiple sclerosis (MS)	249:298	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	13	theme	human	196:200	arg1	rIFN-β					219:224	rIFN-β	219:224	rIFN-β	219:224	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	13	theme	human	196:200	arg1	beta					213:216	Recombinant human interferon beta	184:216	Recombinant human interferon beta (rIFN-β)	184:225	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	7	14	theme	renal	1620:1624	arg1	rate					1636:1639	a significantly reduced renal clearance rate	1596:1639	a significantly reduced renal clearance rate	1596:1639	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	3	15	theme	fusion	705:710	arg1	construct					712:720	a fusion construct	703:720	a fusion construct	703:720	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	7	16	theme	Lewis	1489:1493	arg1	rats					1495:1498	Lewis rats	1489:1498	Lewis rats	1489:1498	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	9	17	theme	further	1842:1848	arg1	development					1850:1860	further development	1842:1860	further development	1842:1860	In conclusion, our results clearly demonstrated that SL335-IFN-β-1a is worthy of further development as an alternative long-acting IFN-β therapeutic.
30684504	0	18	theme	anti-serum	136:145	arg1	fab					155:157	a human anti-serum albumin fab	128:157	a human anti-serum albumin fab	128:157	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	3	19	theme	SL335	775:779	arg1	chain					783:787	the SL335 H chain	771:787	the SL335 H chain	771:787	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	2	20	theme	human	504:508	arg1	SL335					495:499	SL335	495:499	SL335	495:499	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	2	20	theme	human	504:508	arg1	molecule					514:521	a human Fab molecule	502:521	a human Fab molecule specific to serum albumin	502:547	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	5	21	theme	human	1186:1190	arg1	HSA					1207:1209	HSA	1207:1209	HSA	1207:1209	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	5	21	theme	human	1186:1190	arg1	albumin					1198:1204	human serum albumin	1186:1204	human serum albumin (HSA)	1186:1210	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	3	22	theme	human	733:737	arg1	cDNA					745:748	human IFN-β cDNA	733:748	human IFN-β cDNA to the C-terminus of the SL335 H chain	733:787	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	0	23	theme	fab	155:157	arg1	fusion					111:116	genetic fusion	103:116	genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β	103:181	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	4	24	gly	glycosylated	941:952	arg1	form					954:957	its N-linked glycosylated form	928:957	its N-linked glycosylated form	928:957	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	7	25	theme	clearance	1626:1634	arg1	rate					1636:1639	a significantly reduced renal clearance rate	1596:1639	a significantly reduced renal clearance rate	1596:1639	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	0	26	theme	fusion	72:77	arg1	protein					79:85	the SL335-IFN-β-1a fusion protein	53:85	the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β	53:181	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	7	27	theme	pharmacokinetic	1453:1467	arg1	analyses					1474:1481	pharmacokinetic (PK) analyses	1453:1481	pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys	1453:1521	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	7	27	theme	pharmacokinetic	1453:1467	arg1	PK					1470:1471	PK	1470:1471	PK	1470:1471	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	4	28	theme	three-step	1044:1053	arg1	process					1070:1076	a three-step chromatography process	1042:1076	a three-step chromatography process	1042:1076	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	5	29	theme	intrinsic	1152:1160	arg1	capabilities					1170:1181	its intrinsic binding capabilities	1148:1181	its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif)	1148:1322	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	8	30	theme	toxicological	1740:1752	arg1	signs					1754:1758	no abnormal toxicological signs	1728:1758	no abnormal toxicological signs	1728:1758	Finally, a four-week repeated dose toxicity study revealed no abnormal toxicological signs.
30684504	3	31	theme	chain	783:787	arg1	C-terminus					757:766	the C-terminus	753:766	the C-terminus of the SL335 H chain	753:787	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	8	32	theme	repeated	1690:1697	arg1	study					1713:1717	a four-week repeated dose toxicity study	1678:1717	a four-week repeated dose toxicity study	1678:1717	Finally, a four-week repeated dose toxicity study revealed no abnormal toxicological signs.
30684504	2	33	theme	serum	571:575	arg1	half-life					577:585	an extended serum half-life	559:585	an extended serum half-life	559:585	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	5	34	theme	α/β	1227:1229	arg1	IFNAR					1241:1245	IFNAR	1241:1245	IFNAR	1241:1245	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	5	34	theme	α/β	1227:1229	arg1	receptor					1231:1238	interferon α/β receptor	1216:1238	interferon α/β receptor (IFNAR)	1216:1246	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	8	35	theme	toxicity	1704:1711	arg1	study					1713:1717	a four-week repeated dose toxicity study	1678:1717	a four-week repeated dose toxicity study	1678:1717	Finally, a four-week repeated dose toxicity study revealed no abnormal toxicological signs.
30684504	2	36	theme	recycling	610:618	arg1	mechanism					620:628	the FcRn recycling mechanism	601:628	the FcRn recycling mechanism	601:628	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	0	37	theme	Intact	0:5	arg1	bioactivities					7:19	Intact bioactivities	0:19	Intact bioactivities	0:19	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	3	38	theme	fusion	836:841	arg1	protein					843:849	the fusion protein	832:849	the fusion protein	832:849	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	6	39	dep	potency	1380:1386	arg1	an					1367:1368	an	1367:1368	an	1367:1368	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	5	40	theme	In	1079:1080	arg1	assays					1099:1104	In vitro functional assays	1079:1104	In vitro functional assays	1079:1104	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	1	41	from	clinics	457:463	arg1	available					444:452	available	444:452	available	444:452	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	42	theme	multiple	276:283	arg1	sclerosis					285:293	multiple sclerosis	276:293	multiple sclerosis (MS)	276:298	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	42	theme	multiple	276:283	arg1	MS					296:297	MS	296:297	MS	296:297	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	6	43	contain	possessed	1357:1365	arg2	activity					1411:1418	anti-proliferation activity	1392:1418	anti-proliferation activity	1392:1418	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	6	43	contain	possessed	1357:1365	arg1	protein					1349:1355	the fusion protein	1338:1355	the fusion protein	1338:1355	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	6	43	contain	possessed	1357:1365	arg2	potency					1380:1386	antiviral potency	1370:1386	antiviral potency	1370:1386	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	1	44	from	available	444:452	arg1	clinics					457:463	clinics	457:463	clinics	457:463	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	4	45	theme	fusion	974:979	arg1	protein					981:987	the resulting fusion protein	960:987	the resulting fusion protein	960:987	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	4	46	theme	N-linked	932:939	arg1	form					954:957	its N-linked glycosylated form	928:957	its N-linked glycosylated form	928:957	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	3	47	theme	ultimate	640:647	arg1	goal					649:652	the ultimate goal	636:652	the ultimate goal of developing a long-acting rIFN-®	636:687	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	0	48	theme	human	164:168	arg1	interferon-β					170:181	human interferon-β	164:181	human interferon-β	164:181	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	5	49	theme	functional	1088:1097	arg1	assays					1099:1104	In vitro functional assays	1079:1104	In vitro functional assays	1079:1104	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	2	50	theme	serum	535:539	arg1	albumin					541:547	serum albumin	535:547	serum albumin	535:547	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	2	51	theme	specific	523:530	arg1	SL335					495:499	SL335	495:499	SL335	495:499	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	2	51	theme	specific	523:530	arg1	molecule					514:521	a human Fab molecule	502:521	a human Fab molecule specific to serum albumin	502:547	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	3	52	theme	hamster	894:900	arg1	cells					918:922	Chinese hamster ovary-S (CHO-S) cells	886:922	Chinese hamster ovary-S (CHO-S) cells	886:922	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	1	53	theme	rIFN-β-1a	410:418	arg1	version					387:393	only one pegylated version	368:393	only one pegylated version of long-acting rIFN-β-1a (Plegridy)	368:429	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	6	54	theme	comparable	1420:1429	arg1	potency					1380:1386	antiviral potency	1370:1386	antiviral potency	1370:1386	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	5	55	theme	parental	1287:1294	arg1	SL335					1296:1300	parental SL335	1287:1300	parental SL335	1287:1300	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	6	56	theme	anti-proliferation	1392:1409	arg1	activity					1411:1418	anti-proliferation activity	1392:1418	anti-proliferation activity	1392:1418	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	7	57	theme	cynomolgus	1504:1513	arg1	monkeys					1515:1521	cynomolgus monkeys	1504:1521	cynomolgus monkeys	1504:1521	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	1	58	theme	Recombinant	184:194	arg1	treatment					262:270	a first-line treatment	249:270	a first-line treatment for multiple sclerosis (MS)	249:298	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	58	theme	Recombinant	184:194	arg1	rIFN-β					219:224	rIFN-β	219:224	rIFN-β	219:224	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	58	theme	Recombinant	184:194	arg1	beta					213:216	Recombinant human interferon beta	184:216	Recombinant human interferon beta (rIFN-β)	184:225	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	0	59	theme	human	130:134	arg1	fab					155:157	a human anti-serum albumin fab	128:157	a human anti-serum albumin fab	128:157	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	7	60	theme	serum	1576:1580	arg1	half-life					1582:1590	a two-fold longer serum half-life	1558:1590	a two-fold longer serum half-life	1558:1590	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	1	61	theme	interferon	202:211	arg1	treatment					262:270	a first-line treatment	249:270	a first-line treatment for multiple sclerosis (MS)	249:298	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	61	theme	interferon	202:211	arg1	rIFN-β					219:224	rIFN-β	219:224	rIFN-β	219:224	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	61	theme	interferon	202:211	arg1	beta					213:216	Recombinant human interferon beta	184:216	Recombinant human interferon beta (rIFN-β)	184:225	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	0	62	theme	albumin	147:153	arg1	fab					155:157	a human anti-serum albumin fab	128:157	a human anti-serum albumin fab	128:157	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	2	63	theme	Fab	510:512	arg1	SL335					495:499	SL335	495:499	SL335	495:499	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	2	63	theme	Fab	510:512	arg1	molecule					514:521	a human Fab molecule	502:521	a human Fab molecule specific to serum albumin	502:547	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	9	64	theme	development	1850:1860	arg1	worthy					1832:1837	worthy	1832:1837	worthy of further development	1832:1860	In conclusion, our results clearly demonstrated that SL335-IFN-β-1a is worthy of further development as an alternative long-acting IFN-β therapeutic.
30684504	3	65	theme	H	781:781	arg1	chain					783:787	the SL335 H chain	771:787	the SL335 H chain	771:787	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	5	66	theme	serum	1192:1196	arg1	HSA					1207:1209	HSA	1207:1209	HSA	1207:1209	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	5	66	theme	serum	1192:1196	arg1	albumin					1198:1204	human serum albumin	1186:1204	human serum albumin (HSA)	1186:1210	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	3	67	theme	IFN-β	739:743	arg1	cDNA					745:748	human IFN-β cDNA	733:748	human IFN-β cDNA to the C-terminus of the SL335 H chain	733:787	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	0	68	theme	protein	79:85	arg1	pharmacokinetic					34:48	pharmacokinetic	34:48	pharmacokinetic	34:48	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	1	69	theme	pegylated	377:385	arg1	version					387:393	only one pegylated version	368:393	only one pegylated version of long-acting rIFN-β-1a (Plegridy)	368:429	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	7	70	theme	reduced	1612:1618	arg1	rate					1636:1639	a significantly reduced renal clearance rate	1596:1639	a significantly reduced renal clearance rate	1596:1639	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	5	71	dep	In	1079:1080	arg1	vitro					1082:1086	vitro	1082:1086	vitro	1082:1086	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	3	72	from	expression	818:827	arg1	cells					918:922	Chinese hamster ovary-S (CHO-S) cells	886:922	Chinese hamster ovary-S (CHO-S) cells	886:922	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	4	73	theme	chromatography	1055:1068	arg1	process					1070:1076	a three-step chromatography process	1042:1076	a three-step chromatography process	1042:1076	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
30684504	3	74	theme	DNA	796:798	arg1	level					800:804	the DNA level	792:804	the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells	792:922	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	5	75	theme	binding	1162:1168	arg1	capabilities					1170:1181	its intrinsic binding capabilities	1148:1181	its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif)	1148:1322	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	0	76	theme	genetic	103:109	arg1	fusion					111:116	genetic fusion	103:116	genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β	103:181	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	5	77	theme	interferon	1216:1225	arg1	IFNAR					1241:1245	IFNAR	1241:1245	IFNAR	1241:1245	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	5	77	theme	interferon	1216:1225	arg1	receptor					1231:1238	interferon α/β receptor	1216:1238	interferon α/β receptor (IFNAR)	1216:1246	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	8	78	theme	four-week	1680:1688	arg1	study					1713:1717	a four-week repeated dose toxicity study	1678:1717	a four-week repeated dose toxicity study	1678:1717	Finally, a four-week repeated dose toxicity study revealed no abnormal toxicological signs.
30684504	7	79	theme	longer	1569:1574	arg1	half-life					1582:1590	a two-fold longer serum half-life	1558:1590	a two-fold longer serum half-life	1558:1590	In pharmacokinetic (PK) analyses using Lewis rats and cynomolgus monkeys, SL335-IFN-β-1a exhibited at least a two-fold longer serum half-life and a significantly reduced renal clearance rate compared to those of Rebif.
30684504	8	80	theme	dose	1699:1702	arg1	study					1713:1717	a four-week repeated dose toxicity study	1678:1717	a four-week repeated dose toxicity study	1678:1717	Finally, a four-week repeated dose toxicity study revealed no abnormal toxicological signs.
30684504	2	81	theme	FcRn	605:608	arg1	mechanism					620:628	the FcRn recycling mechanism	601:628	the FcRn recycling mechanism	601:628	Previously, we reported that SL335, a human Fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the FcRn recycling mechanism.
30684504	1	82	theme	first-line	251:260	arg1	treatment					262:270	a first-line treatment	249:270	a first-line treatment for multiple sclerosis (MS)	249:298	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	82	theme	first-line	251:260	arg1	beta					213:216	Recombinant human interferon beta	184:216	Recombinant human interferon beta (rIFN-β)	184:225	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	3	83	theme	protein	843:849	arg1	expression					818:827	expression	818:827	expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells	818:922	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	1	84	used	used	241:244	arg2	beta					213:216	Recombinant human interferon beta	184:216	Recombinant human interferon beta (rIFN-β)	184:225	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	84	used	used	241:244	arg2	rIFN-β					219:224	rIFN-β	219:224	rIFN-β	219:224	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	1	84	used	used	241:244	arg2	treatment					262:270	a first-line treatment	249:270	a first-line treatment for multiple sclerosis (MS)	249:298	Recombinant human interferon beta (rIFN-β) has long been used as a first-line treatment for multiple sclerosis (MS), and any attempt to develop a long-acting rIFN-β is desirable since only one pegylated version of long-acting rIFN-β-1a (Plegridy) is currently available in clinics.
30684504	0	85	theme	SL335-IFN-β-1a	57:70	arg1	protein					79:85	the SL335-IFN-β-1a fusion protein	53:85	the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β	53:181	Intact bioactivities and improved pharmacokinetic of the SL335-IFN-β-1a fusion protein that created by genetic fusion of SL335, a human anti-serum albumin fab, and human interferon-β.
30684504	6	86	theme	fusion	1342:1347	arg1	protein					1349:1355	the fusion protein	1338:1355	the fusion protein	1338:1355	In addition, the fusion protein possessed an antiviral potency and anti-proliferation activity comparable to those of Rebif.
30684504	5	87	theme	fusion	1124:1129	arg1	protein					1131:1137	the fusion protein	1120:1137	the fusion protein	1120:1137	In vitro functional assays revealed that the fusion protein retained its intrinsic binding capabilities to human serum albumin (HSA) and interferon α/β receptor (IFNAR) that were almost identical to those of parental SL335 and rIFN-β-1a (Rebif).
30684504	3	88	theme	Chinese	886:892	arg1	cells					918:922	Chinese hamster ovary-S (CHO-S) cells	886:922	Chinese hamster ovary-S (CHO-S) cells	886:922	With the ultimate goal of developing a long-acting rIFN-®, we generated a fusion construct by linking human IFN-β cDNA to the C-terminus of the SL335 H chain at the DNA level followed by expression of the fusion protein, referred to as SL335-IFN-β-1a, in Chinese hamster ovary-S (CHO-S) cells.
30684504	4	89	theme	resulting	964:972	arg1	protein					981:987	the resulting fusion protein	960:987	the resulting fusion protein	960:987	In its N-linked glycosylated form, the resulting fusion protein was easily purified from the culture supernatant via a three-step chromatography process.
28364041	10	0	with	interactions	1829:1840	arg1	galectin-3					1859:1868	circulating galectin-3	1847:1868	circulating galectin-3	1847:1868	We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
28364041	3	1	theme	cytokines	729:737	arg1	secretion					687:695	endothelial secretion	675:695	endothelial secretion of several metastasis-promoting cytokines	675:737	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	9	2	from	ligand	1685:1690	arg1	surfaces					1712:1719	endothelial cell surfaces	1695:1719	endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines	1695:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	0	3	from	cells	158:162	arg1	secretion					88:96	secretion	88:96	secretion of metastasis-promoting cytokines from vascular endothelial cells	88:162	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	9	4	theme	responsible	1721:1731	arg1	surfaces					1712:1719	endothelial cell surfaces	1695:1719	endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines	1695:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	5	5	theme	cell	976:979	arg1	CD144/VE-cadherin					1119:1135	CD144/VE-cadherin	1119:1135	CD144/VE-cadherin	1119:1135	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	5	theme	cell	976:979	arg1	CD106/Endoglin					1142:1155	CD106/Endoglin	1142:1155	CD106/Endoglin	1142:1155	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	5	theme	cell	976:979	arg1	molecule					1034:1041	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	5	theme	cell	976:979	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	5	theme	cell	976:979	arg1	molecule-1					1097:1106	CD31/platelet endothelial cell adhesion molecule-1	1057:1106	CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1)	1057:1116	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	1	6	theme	protein	189:195	arg1	galectin-3					197:206	The galactoside-binding protein galectin-3	165:206	The galactoside-binding protein galectin-3	165:206	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	1	6	theme	protein	189:195	arg1	player					251:256	an important player	238:256	an important player in cancer development, progression, and metastasis	238:307	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	8	7	theme	siRNA-mediated	1474:1487	arg1	suppression					1489:1499	siRNA-mediated suppression	1474:1499	siRNA-mediated suppression of CD146 expression	1474:1519	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	0	8	theme	metastasis-promoting	101:120	arg1	cytokines					122:130	metastasis-promoting cytokines	101:130	metastasis-promoting cytokines	101:130	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	5	9	theme	different	904:912	arg1	processes					947:955	two different galectin-3 affinity purification processes	900:955	two different galectin-3 affinity purification processes	900:955	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	6	10	theme	exogenous	1321:1329	arg1	galectin-3					1331:1340	exogenous galectin-3	1321:1340	exogenous galectin-3	1321:1340	CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3.
28364041	0	11	theme	endothelial	146:156	arg1	cells					158:162	vascular endothelial cells	137:162	vascular endothelial cells	137:162	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	3	12	theme	receptor	622:629	arg1	s					631:631	unknown receptor(s)	614:632	unknown receptor(s) on vascular endothelial cells	614:662	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	5	13	theme	membrane	981:988	arg1	CD144/VE-cadherin					1119:1135	CD144/VE-cadherin	1119:1135	CD144/VE-cadherin	1119:1135	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	13	theme	membrane	981:988	arg1	CD106/Endoglin					1142:1155	CD106/Endoglin	1142:1155	CD106/Endoglin	1142:1155	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	13	theme	membrane	981:988	arg1	molecule					1034:1041	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	13	theme	membrane	981:988	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	13	theme	membrane	981:988	arg1	molecule-1					1097:1106	CD31/platelet endothelial cell adhesion molecule-1	1057:1106	CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1)	1057:1116	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	7	14	theme	signaling	1463:1471	arg1	dimerization					1417:1428	CD146 dimerization	1411:1428	CD146 dimerization	1411:1428	Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling.
28364041	7	14	theme	signaling	1463:1471	arg1	activation					1445:1454	subsequent activation	1434:1454	subsequent activation of AKT signaling	1434:1471	Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling.
28364041	9	15	theme	galectin-3-induced	1737:1754	arg1	secretion					1756:1764	galectin-3-induced secretion	1737:1764	galectin-3-induced secretion of metastasis-promoting cytokines	1737:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	1	16	from	player	251:256	arg1	progression					281:291	progression	281:291	progression	281:291	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	1	16	from	player	251:256	arg1	metastasis					298:307	metastasis	298:307	metastasis	298:307	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	1	16	from	player	251:256	arg1	development					268:278	cancer development	261:278	cancer development	261:278	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	3	17	theme	endothelial	646:656	arg1	cells					658:662	vascular endothelial cells	637:662	vascular endothelial cells	637:662	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	6	18	theme	cell	1294:1297	arg1	surfaces					1299:1306	endothelial cell surfaces	1282:1306	endothelial cell surfaces treated with exogenous galectin-3	1282:1340	CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3.
28364041	9	19	theme	functional	1655:1664	arg1	CD146/MCAM					1637:1646	CD146/MCAM	1637:1646	CD146/MCAM	1637:1646	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	9	19	theme	functional	1655:1664	arg1	ligand					1685:1690	the functional galectin-3-binding ligand	1651:1690	the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines	1651:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	2	20	theme	animal	520:525	arg1	model					534:538	an animal cancer model	517:538	an animal cancer model	517:538	We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model.
28364041	8	21	from	cells	1624:1628	arg1	secretion					1565:1573	the galectin-3-induced secretion	1542:1573	the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells	1542:1628	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	5	22	theme	vascular	1163:1170	arg1	cells					1184:1188	vascular endothelial cells	1163:1188	vascular endothelial cells	1163:1188	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	9	23	theme	endothelial	1695:1705	arg1	surfaces					1712:1719	endothelial cell surfaces	1695:1719	endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines	1695:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	4	24	theme	endothelial	809:819	arg1	surface					826:832	the endothelial cell surface	805:832	the endothelial cell surface	805:832	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	4	25	from	s	799:799	arg1	surface					826:832	the endothelial cell surface	805:832	the endothelial cell surface	805:832	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	4	26	theme	molecule	790:797	arg1	s					799:799	the galectin-3-binding molecule(s)	767:800	the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion	767:891	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	5	27	theme	cell	1020:1023	arg1	MCAM					1044:1047	MCAM	1044:1047	MCAM	1044:1047	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	27	theme	cell	1020:1023	arg1	molecule					1034:1041	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	27	theme	cell	1020:1023	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	2	28	theme	cancer	465:470	arg1	patients					472:479	cancer patients	465:479	cancer patients	465:479	We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model.
28364041	10	29	theme	important	1882:1890	arg1	influence					1892:1900	an important influence	1879:1900	an important influence	1879:1900	We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
28364041	3	30	theme	endothelial	675:685	arg1	secretion					687:695	endothelial secretion	675:695	endothelial secretion of several metastasis-promoting cytokines	675:737	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	4	31	theme	galectin-3-mediated	854:872	arg1	secretion					883:891	the galectin-3-mediated cytokine secretion	850:891	the galectin-3-mediated cytokine secretion	850:891	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	3	32	from	s	631:631	arg1	cells					658:662	vascular endothelial cells	637:662	vascular endothelial cells	637:662	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	1	33	theme	galactoside-binding	169:187	arg1	galectin-3					197:206	The galactoside-binding protein galectin-3	165:206	The galactoside-binding protein galectin-3	165:206	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	1	33	theme	galactoside-binding	169:187	arg1	player					251:256	an important player	238:256	an important player in cancer development, progression, and metastasis	238:307	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	0	34	theme	cell-surface	30:41	arg1	glycoprotein					43:54	the cell-surface glycoprotein CD146	26:60	the cell-surface glycoprotein CD146 (MCAM, MUC18)	26:74	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	9	35	theme	metastasis-promoting	1769:1788	arg1	cytokines					1790:1798	metastasis-promoting cytokines	1769:1798	metastasis-promoting cytokines	1769:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	2	36	theme	blood-borne	491:501	arg1	metastasis					503:512	blood-borne metastasis	491:512	blood-borne metastasis	491:512	We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model.
28364041	2	37	dep	30-fold	454:460	arg1	up					448:449	up	448:449	up	448:449	We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model.
28364041	1	38	theme	various	335:341	arg1	glycans					366:372	various galactoside-terminated glycans	335:372	various galactoside-terminated glycans	335:372	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	6	39	theme	endothelial	1282:1292	arg1	surfaces					1299:1306	endothelial cell surfaces	1282:1306	endothelial cell surfaces treated with exogenous galectin-3	1282:1340	CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3.
28364041	3	40	theme	metastasis-promoting	708:727	arg1	cytokines					729:737	several metastasis-promoting cytokines	700:737	several metastasis-promoting cytokines	700:737	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	1	41	theme	important	241:249	arg1	galectin-3					197:206	The galactoside-binding protein galectin-3	165:206	The galactoside-binding protein galectin-3	165:206	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	1	41	theme	important	241:249	arg1	player					251:256	an important player	238:256	an important player in cancer development, progression, and metastasis	238:307	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	5	42	theme	CD31/platelet	1057:1069	arg1	molecule-1					1097:1106	CD31/platelet endothelial cell adhesion molecule-1	1057:1106	CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1)	1057:1116	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	42	theme	CD31/platelet	1057:1069	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	42	theme	CD31/platelet	1057:1069	arg1	PECAM-1					1109:1115	PECAM-1	1109:1115	PECAM-1	1109:1115	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	7	43	theme	N-linked	1373:1380	arg1	glycans					1382:1388	N-linked glycans	1373:1388	N-linked glycans	1373:1388	Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling.
28364041	8	44	theme	IL-6	1578:1581	arg1	secretion					1565:1573	the galectin-3-induced secretion	1542:1573	the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells	1542:1628	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	2	45	theme	circulating	405:415	arg1	galectin-3					417:426	circulating galectin-3	405:426	circulating galectin-3	405:426	We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model.
28364041	5	46	theme	affinity	925:932	arg1	processes					947:955	two different galectin-3 affinity purification processes	900:955	two different galectin-3 affinity purification processes	900:955	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	47	theme	cell	1083:1086	arg1	molecule-1					1097:1106	CD31/platelet endothelial cell adhesion molecule-1	1057:1106	CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1)	1057:1116	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	47	theme	cell	1083:1086	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	47	theme	cell	1083:1086	arg1	PECAM-1					1109:1115	PECAM-1	1109:1115	PECAM-1	1109:1115	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	9	48	theme	cytokines	1790:1798	arg1	secretion					1756:1764	galectin-3-induced secretion	1737:1764	galectin-3-induced secretion of metastasis-promoting cytokines	1737:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	1	49	with	interactions	317:328	arg1	glycans					366:372	various galactoside-terminated glycans	335:372	various galactoside-terminated glycans	335:372	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	5	50	theme	galectin-3	914:923	arg1	processes					947:955	two different galectin-3 affinity purification processes	900:955	two different galectin-3 affinity purification processes	900:955	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	10	51	contain	have	1874:1877	arg2	influence					1892:1900	an important influence	1879:1900	an important influence	1879:1900	We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
28364041	10	51	contain	have	1874:1877	arg1	interactions					1829:1840	CD146/MCAM interactions	1818:1840	CD146/MCAM interactions with circulating galectin-3	1818:1868	We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
28364041	3	52	theme	galectin-3	598:607	arg1	interaction					583:593	the interaction	579:593	the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells	579:662	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	5	53	theme	purification	934:945	arg1	processes					947:955	two different galectin-3 affinity purification processes	900:955	two different galectin-3 affinity purification processes	900:955	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	0	54	gly	glycoprotein	43:54	arg1	glycoprotein					43:54	the cell-surface glycoprotein CD146	26:60	the cell-surface glycoprotein CD146 (MCAM, MUC18)	26:74	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	0	55	theme	cytokines	122:130	arg1	secretion					88:96	secretion	88:96	secretion of metastasis-promoting cytokines from vascular endothelial cells	88:162	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	8	56	theme	G-CSF	1587:1591	arg1	secretion					1565:1573	the galectin-3-induced secretion	1542:1573	the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells	1542:1628	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	6	57	theme	galectin-3-binding	1211:1228	arg1	ligand					1230:1235	the major galectin-3-binding ligand	1201:1235	the major galectin-3-binding ligand	1201:1235	CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3.
28364041	6	57	theme	galectin-3-binding	1211:1228	arg1	CD146					1191:1195	CD146	1191:1195	CD146	1191:1195	CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3.
28364041	10	58	theme	CD146/MCAM	1818:1827	arg1	interactions					1829:1840	CD146/MCAM interactions	1818:1840	CD146/MCAM interactions with circulating galectin-3	1818:1868	We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
28364041	0	59	theme	vascular	137:144	arg1	cells					158:162	vascular endothelial cells	137:162	vascular endothelial cells	137:162	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	5	60	gly	glycoproteins	990:1002	arg1	CD144/VE-cadherin					1119:1135	CD144/VE-cadherin	1119:1135	CD144/VE-cadherin	1119:1135	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	60	gly	glycoproteins	990:1002	arg1	CD106/Endoglin					1142:1155	CD106/Endoglin	1142:1155	CD106/Endoglin	1142:1155	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	60	gly	glycoproteins	990:1002	arg1	molecule					1034:1041	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	60	gly	glycoproteins	990:1002	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	60	gly	glycoproteins	990:1002	arg1	molecule-1					1097:1106	CD31/platelet endothelial cell adhesion molecule-1	1057:1106	CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1)	1057:1116	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	3	61	theme	unknown	614:620	arg1	s					631:631	unknown receptor(s)	614:632	unknown receptor(s) on vascular endothelial cells	614:662	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	8	62	dep	IL-6	1578:1581	arg1	cytokines					1593:1601	cytokines	1593:1601	cytokines	1593:1601	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	7	63	link	N-linked	1373:1380	arg1	glycans					1382:1388	N-linked glycans	1373:1388	N-linked glycans	1373:1388	Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling.
28364041	8	64	theme	endothelial	1612:1622	arg1	cells					1624:1628	the endothelial cells	1608:1628	the endothelial cells	1608:1628	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	3	65	theme	vascular	637:644	arg1	cells					658:662	vascular endothelial cells	637:662	vascular endothelial cells	637:662	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	2	66	theme	cancer	527:532	arg1	model					534:538	an animal cancer model	517:538	an animal cancer model	517:538	We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model.
28364041	7	67	theme	AKT	1459:1461	arg1	signaling					1463:1471	AKT signaling	1459:1471	AKT signaling	1459:1471	Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling.
28364041	9	68	theme	galectin-3-binding	1666:1683	arg1	CD146/MCAM					1637:1646	CD146/MCAM	1637:1646	CD146/MCAM	1637:1646	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	9	68	theme	galectin-3-binding	1666:1683	arg1	ligand					1685:1690	the functional galectin-3-binding ligand	1651:1690	the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines	1651:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	8	69	theme	galectin-3-induced	1546:1563	arg1	secretion					1565:1573	the galectin-3-induced secretion	1542:1573	the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells	1542:1628	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	5	70	theme	endothelial	1172:1182	arg1	cells					1184:1188	vascular endothelial cells	1163:1188	vascular endothelial cells	1163:1188	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	9	71	theme	cell	1707:1710	arg1	surfaces					1712:1719	endothelial cell surfaces	1695:1719	endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines	1695:1798	Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines.
28364041	7	72	theme	subsequent	1434:1443	arg1	activation					1445:1454	subsequent activation	1434:1454	subsequent activation of AKT signaling	1434:1471	Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling.
28364041	10	73	theme	circulating	1847:1857	arg1	galectin-3					1859:1868	circulating galectin-3	1847:1868	circulating galectin-3	1847:1868	We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
28364041	3	74	with	interaction	583:593	arg1	s					631:631	unknown receptor(s)	614:632	unknown receptor(s) on vascular endothelial cells	614:662	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	5	75	theme	CD146/melanoma	1005:1018	arg1	MCAM					1044:1047	MCAM	1044:1047	MCAM	1044:1047	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	75	theme	CD146/melanoma	1005:1018	arg1	molecule					1034:1041	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	75	theme	CD146/melanoma	1005:1018	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	4	76	theme	galectin-3-binding	771:788	arg1	s					799:799	the galectin-3-binding molecule(s)	767:800	the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion	767:891	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	5	77	theme	adhesion	1025:1032	arg1	MCAM					1044:1047	MCAM	1044:1047	MCAM	1044:1047	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	77	theme	adhesion	1025:1032	arg1	molecule					1034:1041	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	CD146/melanoma cell adhesion molecule (MCAM)/MUC18	1005:1054	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	77	theme	adhesion	1025:1032	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	78	theme	adhesion	1088:1095	arg1	molecule-1					1097:1106	CD31/platelet endothelial cell adhesion molecule-1	1057:1106	CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1)	1057:1116	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	78	theme	adhesion	1088:1095	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	78	theme	adhesion	1088:1095	arg1	PECAM-1					1109:1115	PECAM-1	1109:1115	PECAM-1	1109:1115	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	8	79	theme	expression	1510:1519	arg1	suppression					1489:1499	siRNA-mediated suppression	1474:1499	siRNA-mediated suppression of CD146 expression	1474:1519	siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells.
28364041	0	80	dep	glycoprotein	43:54	arg1	MUC18					69:73	MUC18	69:73	MUC18	69:73	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	0	80	dep	glycoprotein	43:54	arg1	MCAM					63:66	MCAM	63:66	MCAM	63:66	Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
28364041	6	81	theme	major	1205:1209	arg1	ligand					1230:1235	the major galectin-3-binding ligand	1201:1235	the major galectin-3-binding ligand	1201:1235	CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3.
28364041	6	81	theme	major	1205:1209	arg1	CD146					1191:1195	CD146	1191:1195	CD146	1191:1195	CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3.
28364041	3	82	theme	several	700:706	arg1	cytokines					729:737	several metastasis-promoting cytokines	700:737	several metastasis-promoting cytokines	700:737	This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines.
28364041	4	83	theme	cytokine	874:881	arg1	secretion					883:891	the galectin-3-mediated cytokine secretion	850:891	the galectin-3-mediated cytokine secretion	850:891	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	10	84	theme	cancer	1905:1910	arg1	progression					1912:1922	cancer progression	1905:1922	cancer progression	1905:1922	We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.
28364041	1	85	theme	galactoside-terminated	343:364	arg1	glycans					366:372	various galactoside-terminated glycans	335:372	various galactoside-terminated glycans	335:372	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
28364041	4	86	theme	cell	821:824	arg1	surface					826:832	the endothelial cell surface	805:832	the endothelial cell surface	805:832	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	5	87	theme	endothelial	1071:1081	arg1	molecule-1					1097:1106	CD31/platelet endothelial cell adhesion molecule-1	1057:1106	CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1)	1057:1116	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	87	theme	endothelial	1071:1081	arg1	glycoproteins					990:1002	four cell membrane glycoproteins	971:1002	four cell membrane glycoproteins	971:1002	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	5	87	theme	endothelial	1071:1081	arg1	PECAM-1					1109:1115	PECAM-1	1109:1115	PECAM-1	1109:1115	Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells.
28364041	4	88	theme	responsible	834:844	arg1	s					799:799	the galectin-3-binding molecule(s)	767:800	the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion	767:891	Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion.
28364041	1	89	theme	cancer	261:266	arg1	development					268:278	cancer development	261:278	cancer development	261:278	The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans.
31540487	0	0	from	Profiling	15:23	arg1	Shell					82:86	the Pteria Penguin Pearl Shell	57:86	the Pteria Penguin Pearl Shell	57:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	6	1	link	N-linked	1151:1158	arg1	glycans					1160:1166	high-mannose-and hybrid-type N-linked glycans	1122:1166	high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans	1122:1223	On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
31540487	1	2	theme	sequence	217:224	arg1	α					242:242	α	242:242	α	242:242	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	2	theme	sequence	217:224	arg1	variants					226:233	sequence variants α + α	217:239	variants	226:233	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	2	theme	sequence	217:224	arg1	β					246:246	β	246:246	β	246:246	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	0	3	theme	Pearl	76:80	arg1	Shell					82:86	the Pteria Penguin Pearl Shell	57:86	the Pteria Penguin Pearl Shell	57:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	3	4	theme	chromatography	760:773	arg1	analysis					775:782	frontal affinity chromatography analysis	743:782	frontal affinity chromatography analysis	743:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	3	5	theme	data	728:731	arg1	sets					733:736	the multiple glycan binding profiling data sets	690:736	the multiple glycan binding profiling data sets from frontal affinity chromatography analysis	690:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	2	6	theme	matrix	524:529	arg1	PPL2A					482:486	PPL2A	482:486	PPL2A	482:486	Their carbohydrate-binding properties were analyzed, in addition to that of PPL2A, which was previously reported as a matrix protein.
31540487	2	6	theme	matrix	524:529	arg1	protein					531:537	a matrix protein	522:537	a matrix protein	522:537	Their carbohydrate-binding properties were analyzed, in addition to that of PPL2A, which was previously reported as a matrix protein.
31540487	6	7	theme	high-mannose-and	1122:1137	arg1	glycans					1160:1166	high-mannose-and hybrid-type N-linked glycans	1122:1166	high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans	1122:1223	On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
31540487	3	8	theme	glycan	703:708	arg1	sets					733:736	the multiple glycan binding profiling data sets	690:736	the multiple glycan binding profiling data sets from frontal affinity chromatography analysis	690:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	4	9	theme	carbohydrate-binding	942:961	arg1	specificity					963:973	different carbohydrate-binding specificity	932:973	different carbohydrate-binding specificity	932:973	The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s.
31540487	3	10	from	analysis	775:782	arg1	sets					733:736	the multiple glycan binding profiling data sets	690:736	the multiple glycan binding profiling data sets from frontal affinity chromatography analysis	690:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	3	11	theme	binding	710:716	arg1	sets					733:736	the multiple glycan binding profiling data sets	690:736	the multiple glycan binding profiling data sets from frontal affinity chromatography analysis	690:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	1	12	theme	mantle	345:350	arg1	fluid					362:366	mantle secretory fluid	345:366	mantle secretory fluid of Pteria penguin (Mabe) pearl shell	345:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	5	13	theme	agalactosylated-	1039:1054	arg1	glycans					1080:1086	agalactosylated- and galactosylated-type glycans	1039:1086	agalactosylated- and galactosylated-type glycans	1039:1086	PPL2A and PPL3s mainly recognize agalactosylated- and galactosylated-type glycans.
31540487	3	14	theme	profiling	718:726	arg1	sets					733:736	the multiple glycan binding profiling data sets	690:736	the multiple glycan binding profiling data sets from frontal affinity chromatography analysis	690:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	1	15	theme	secretory	352:360	arg1	fluid					362:366	mantle secretory fluid	345:366	mantle secretory fluid of Pteria penguin (Mabe) pearl shell	345:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	4	16	theme	different	932:940	arg1	specificity					963:973	different carbohydrate-binding specificity	932:973	different carbohydrate-binding specificity	932:973	The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s.
31540487	0	17	theme	Binding	7:13	arg1	Profiling					15:23	Glycan Binding Profiling	0:23	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell	0:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	4	18	theme	Man3Fuc1Xyl1GlcNAc2	877:895	arg1	oligosaccharide					897:911	Man3Fuc1Xyl1GlcNAc2 oligosaccharide	877:911	Man3Fuc1Xyl1GlcNAc2 oligosaccharide	877:911	The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s.
31540487	1	19	dep	PPL3s	160:164	arg1	3B					174:175	3B	174:175	3B	174:175	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	19	dep	PPL3s	160:164	arg1	3C					182:183	3C	182:183	3C	182:183	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	19	dep	PPL3s	160:164	arg1	PPL3A					167:171	PPL3A	167:171	PPL3A	167:171	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	19	dep	PPL3s	160:164	arg1	dimers					196:201	dimers	196:201	dimers consisting of sequence variants α + α, α + β	196:246	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	0	20	theme	Glycan	0:5	arg1	Profiling					15:23	Glycan Binding Profiling	0:23	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell	0:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	1	21	theme	Pteria	371:376	arg1	shell					399:403	Pteria penguin (Mabe) pearl shell	371:403	Pteria penguin (Mabe) pearl shell	371:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	6	22	theme	other	1096:1100	arg1	hand					1102:1105	the other hand	1092:1105	the other hand	1092:1105	On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
31540487	0	23	from	Shell	82:86	arg1	Profiling					15:23	Glycan Binding Profiling	0:23	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell	0:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	0	23	from	Shell	82:86	arg1	Lectins					44:50	Jacalin-Related Lectins	28:50	Jacalin-Related Lectins from the Pteria Penguin Pearl Shell	28:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	0	24	theme	Lectins	44:50	arg1	Profiling					15:23	Glycan Binding Profiling	0:23	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell	0:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	3	25	dep	%	572:572	arg1	35-50					567:571	35-50	567:571	35-50	567:571	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	6	26	theme	galactosylated-type	1197:1215	arg1	glycans					1217:1223	agalactosylated- and galactosylated-type glycans	1176:1223	high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans	1122:1223	On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
31540487	0	27	theme	Jacalin-Related	28:42	arg1	Lectins					44:50	Jacalin-Related Lectins	28:50	Jacalin-Related Lectins from the Pteria Penguin Pearl Shell	28:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	3	28	theme	carbohydrate-binding	646:665	arg1	specificities					667:679	significantly different carbohydrate-binding specificities	622:679	significantly different carbohydrate-binding specificities	622:679	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	2	29	theme	carbohydrate-binding	412:431	arg1	properties					433:442	Their carbohydrate-binding properties	406:442	Their carbohydrate-binding properties	406:442	Their carbohydrate-binding properties were analyzed, in addition to that of PPL2A, which was previously reported as a matrix protein.
31540487	1	30	theme	penguin	378:384	arg1	shell					399:403	Pteria penguin (Mabe) pearl shell	371:403	Pteria penguin (Mabe) pearl shell	371:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	3	31	dep	homology	574:581	arg1	%					572:572	%	572:572	%	572:572	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	6	32	theme	agalactosylated-	1176:1191	arg1	glycans					1217:1223	agalactosylated- and galactosylated-type glycans	1176:1223	high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans	1122:1223	On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
31540487	1	33	theme	primary	107:113	arg1	structures					115:124	the primary structures	103:124	the primary structures	103:124	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	33	theme	primary	107:113	arg1	heterodimer					289:299	heterodimer	289:299	heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell	289:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	4	34	theme	carbohydrate-binding	789:808	arg1	similar					835:841	similar	835:841	similar	835:841	The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s.
31540487	4	34	theme	carbohydrate-binding	789:808	arg1	specificity					810:820	The carbohydrate-binding specificity	785:820	The carbohydrate-binding specificity of PPL3s	785:829	The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s.
31540487	1	35	theme	α	315:315	arg1	subunits					321:328	α + β subunits	315:328	α + β subunits	315:328	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	36	theme	Mabe	387:390	arg1	shell					399:403	Pteria penguin (Mabe) pearl shell	371:403	Pteria penguin (Mabe) pearl shell	371:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	3	37	theme	frontal	743:749	arg1	chromatography					760:773	frontal affinity chromatography	743:773	frontal affinity chromatography analysis	743:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	3	38	theme	different	636:644	arg1	specificities					667:679	significantly different carbohydrate-binding specificities	622:679	significantly different carbohydrate-binding specificities	622:679	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	4	39	theme	PPL3s	825:829	arg1	similar					835:841	similar	835:841	similar	835:841	The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s.
31540487	4	39	theme	PPL3s	825:829	arg1	specificity					810:820	The carbohydrate-binding specificity	785:820	The carbohydrate-binding specificity of PPL3s	785:829	The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s.
31540487	3	40	theme	affinity	751:758	arg1	chromatography					760:773	frontal affinity chromatography	743:773	frontal affinity chromatography analysis	743:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	1	41	theme	β	319:319	arg1	subunits					321:328	α + β subunits	315:328	α + β subunits	315:328	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	42	theme	pearl	393:397	arg1	shell					399:403	Pteria penguin (Mabe) pearl shell	371:403	Pteria penguin (Mabe) pearl shell	371:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	43	theme	jacalin-related	129:143	arg1	lectins					145:151	jacalin-related lectins	129:151	jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4	129:277	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	3	44	theme	multiple	694:701	arg1	sets					733:736	the multiple glycan binding profiling data sets	690:736	the multiple glycan binding profiling data sets from frontal affinity chromatography analysis	690:782	PPL3s and PPL4 shared only 35-50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis.
31540487	0	45	theme	Penguin	68:74	arg1	Shell					82:86	the Pteria Penguin Pearl Shell	57:86	the Pteria Penguin Pearl Shell	57:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	6	46	theme	N-linked	1151:1158	arg1	glycans					1160:1166	high-mannose-and hybrid-type N-linked glycans	1122:1166	high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans	1122:1223	On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
31540487	1	47	theme	shell	399:403	arg1	fluid					362:366	mantle secretory fluid	345:366	mantle secretory fluid of Pteria penguin (Mabe) pearl shell	345:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	48	theme	lectins	145:151	arg1	structures					115:124	the primary structures	103:124	the primary structures	103:124	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	48	theme	lectins	145:151	arg1	heterodimer					289:299	heterodimer	289:299	heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell	289:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	0	49	theme	Pteria	61:66	arg1	Shell					82:86	the Pteria Penguin Pearl Shell	57:86	the Pteria Penguin Pearl Shell	57:86	Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell.
31540487	5	50	theme	galactosylated-type	1060:1078	arg1	glycans					1080:1086	agalactosylated- and galactosylated-type glycans	1039:1086	agalactosylated- and galactosylated-type glycans	1039:1086	PPL2A and PPL3s mainly recognize agalactosylated- and galactosylated-type glycans.
31540487	6	51	theme	hybrid-type	1139:1149	arg1	glycans					1160:1166	high-mannose-and hybrid-type N-linked glycans	1122:1166	high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans	1122:1223	On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
31540487	1	52	attach	isolated	331:338	arg2	subunits					321:328	α + β subunits	315:328	α + β subunits	315:328	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
31540487	1	52	attach	isolated	331:338	arg1	fluid					362:366	mantle secretory fluid	345:366	mantle secretory fluid of Pteria penguin (Mabe) pearl shell	345:403	We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell.
28929344	8	0	theme	p53-null	1607:1614	arg1	cells					1616:1620	both wild-type p53 and p53-null cells	1584:1620	both wild-type p53 and p53-null cells	1584:1620	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	3	1	from	role	467:470	arg1	regulation					489:498	the regulation	485:498	the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells	485:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	1	2	theme	N-linked	234:241	arg1	glycoproteins					243:255	N-linked glycoproteins	234:255	N-linked glycoproteins	234:255	PURPOSE Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins.
28929344	6	3	theme	p53	1225:1227	arg1	cells					1229:1233	only wild-type p53 cells	1210:1233	only wild-type p53 cells	1210:1233	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	3	4	theme	autophagy	503:511	arg1	regulation					489:498	the regulation	485:498	the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells	485:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	4	5	theme	lung	813:816	arg1	cells					828:832	lung carcinoma cells	813:832	lung carcinoma cells differing in p53 status	813:856	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	10	6	theme	status	1981:1986	arg1	independent					1962:1972	independent	1962:1972	independent	1962:1972	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	8	7	from	effect	1553:1558	arg1	cells					1616:1620	both wild-type p53 and p53-null cells	1584:1620	both wild-type p53 and p53-null cells	1584:1620	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	2	8	theme	beta	288:291	arg1	GluIIβ					320:325	GluIIβ	320:325	GluIIβ	320:325	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	2	8	theme	beta	288:291	arg1	subunit					293:299	the beta subunit	284:299	the beta subunit of glucosidase II (GluIIβ) levels	284:333	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	6	9	theme	GluIIβ	1110:1115	arg1	inhibition					1117:1126	GluIIβ inhibition	1110:1126	GluIIβ inhibition	1110:1126	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	0	10	theme	lung	91:94	arg1	cells					106:110	lung carcinoma cells	91:110	lung carcinoma cells	91:110	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	3	11	theme	apoptosis	517:525	arg1	regulation					489:498	the regulation	485:498	the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells	485:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	1	12	theme	major	170:174	arg1	role					176:179	a major role	168:179	a major role	168:179	PURPOSE Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins.
28929344	7	13	theme	pathways	1350:1357	arg1	activation					1300:1309	activation	1300:1309	activation of the EGFR/RTK and PI3K/AKT signaling pathways	1300:1357	We also found that GluIIβ inhibition dose-dependently decreased activation of the EGFR/RTK and PI3K/AKT signaling pathways.
28929344	4	14	theme	glucosidase	625:635	arg1	inhibitor					640:648	A selective glucosidase II inhibitor	613:648	A selective glucosidase II inhibitor	613:648	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	4	14	theme	glucosidase	625:635	arg1	bromoconduritol					651:665	bromoconduritol	651:665	bromoconduritol	651:665	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	6	15	from	apoptosis	1197:1205	arg1	cells					1229:1233	only wild-type p53 cells	1210:1233	only wild-type p53 cells	1210:1233	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	3	16	theme	human	563:567	arg1	cells					598:602	immortalized human bronchial epithelial-derived cells	550:602	immortalized human bronchial epithelial-derived cells	550:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	4	17	from	PRKCSH	803:808	arg1	cells					828:832	lung carcinoma cells	813:832	lung carcinoma cells differing in p53 status	813:856	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	7	18	theme	PI3K/AKT	1331:1338	arg1	pathways					1350:1357	the EGFR/RTK and PI3K/AKT signaling pathways	1314:1357	pathways	1350:1357	We also found that GluIIβ inhibition dose-dependently decreased activation of the EGFR/RTK and PI3K/AKT signaling pathways.
28929344	4	19	theme	GluII	688:692	arg1	activity					701:708	GluII enzyme activity	688:708	GluII enzyme activity	688:708	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	9	20	theme	carcinoma-derived	1719:1735	arg1	cells					1737:1741	lung carcinoma-derived cells	1714:1741	lung carcinoma-derived cells	1714:1741	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	7	21	theme	EGFR/RTK	1318:1325	arg1	activation					1300:1309	activation	1300:1309	activation of the EGFR/RTK and PI3K/AKT signaling pathways	1300:1357	We also found that GluIIβ inhibition dose-dependently decreased activation of the EGFR/RTK and PI3K/AKT signaling pathways.
28929344	6	22	theme	cell	1174:1177	arg1	lines					1179:1183	all cell lines	1170:1183	all cell lines tested	1170:1190	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	5	23	theme	MTT	895:897	arg1	assay					899:903	a MTT assay	893:903	a MTT assay	893:903	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	3	24	theme	epithelial-derived	579:596	arg1	cells					598:602	immortalized human bronchial epithelial-derived cells	550:602	immortalized human bronchial epithelial-derived cells	550:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	5	25	theme	Cell	859:862	arg1	viability					864:872	Cell viability	859:872	Cell viability	859:872	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	3	26	from	regulation	489:498	arg1	carcinoma-					535:544	lung carcinoma-	530:544	lung carcinoma-	530:544	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	3	26	from	regulation	489:498	arg1	cells					598:602	immortalized human bronchial epithelial-derived cells	550:602	immortalized human bronchial epithelial-derived cells	550:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	10	27	theme	cancer	2046:2051	arg1	treatment					2033:2041	the treatment	2029:2041	the treatment of cancer, particularly lung cancer	2029:2077	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	9	28	from	apoptosis	1701:1709	arg1	cells					1737:1741	lung carcinoma-derived cells	1714:1741	lung carcinoma-derived cells	1714:1741	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	2	29	from	role	413:416	arg1	tumorigenesis					426:438	lung tumorigenesis	421:438	lung tumorigenesis	421:438	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	5	30	theme	V-FITC/PI	1054:1062	arg1	method					1080:1085	an annexin V-FITC/PI double labeling method	1043:1085	an annexin V-FITC/PI double labeling method	1043:1085	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	9	31	from	autophagy	1687:1695	arg1	cells					1737:1741	lung carcinoma-derived cells	1714:1741	lung carcinoma-derived cells	1714:1741	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	8	32	theme	lysosomal	1490:1498	arg1	inhibitors					1500:1509	lysosomal inhibitors	1490:1509	lysosomal inhibitors	1490:1509	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	2	33	theme	lung	366:369	arg1	tissues					381:387	lung carcinoma tissues	366:387	lung carcinoma tissues	366:387	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	5	34	theme	labeling	1071:1078	arg1	method					1080:1085	an annexin V-FITC/PI double labeling method	1043:1085	an annexin V-FITC/PI double labeling method	1043:1085	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	4	35	used	used	672:675	arg2	METHODS					605:611	METHODS	605:611	METHODS A selective glucosidase II inhibitor, bromoconduritol,	605:666	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	6	36	from	induction	1144:1152	arg1	lines					1179:1183	all cell lines	1170:1183	all cell lines tested	1170:1190	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	0	37	theme	Glucosidase	0:10	arg1	GluIIβ					29:34	GluIIβ	29:34	GluIIβ	29:34	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	0	37	theme	Glucosidase	0:10	arg1	subunit					20:26	Glucosidase II beta subunit	0:26	Glucosidase II beta subunit (GluIIβ)	0:35	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	2	38	theme	potential	403:411	arg1	role					413:416	a potential role	401:416	a potential role in lung tumorigenesis	401:438	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	0	39	theme	beta	15:18	arg1	GluIIβ					29:34	GluIIβ	29:34	GluIIβ	29:34	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	0	39	theme	beta	15:18	arg1	subunit					20:26	Glucosidase II beta subunit	0:26	Glucosidase II beta subunit (GluIIβ)	0:35	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	5	40	theme	cycle	911:915	arg1	progression					917:927	cell cycle progression	906:927	cell cycle progression	906:927	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	7	41	theme	GluIIβ	1255:1260	arg1	inhibition					1262:1271	GluIIβ inhibition	1255:1271	GluIIβ inhibition	1255:1271	We also found that GluIIβ inhibition dose-dependently decreased activation of the EGFR/RTK and PI3K/AKT signaling pathways.
28929344	8	42	theme	inducing	1383:1390	arg1	p53-dependent					1435:1447	p53-dependent	1435:1447	p53-dependent	1435:1447	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	8	42	theme	inducing	1383:1390	arg1	effect					1392:1397	the apoptosis inducing effect	1369:1397	the apoptosis inducing effect of GluIIβ inhibition	1369:1418	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	4	43	dep	METHODS	605:611	arg1	inhibitor					640:648	A selective glucosidase II inhibitor	613:648	A selective glucosidase II inhibitor	613:648	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	4	43	dep	METHODS	605:611	arg1	bromoconduritol					651:665	bromoconduritol	651:665	bromoconduritol	651:665	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	9	44	theme	suppressive	1831:1841	arg1	processes					1843:1851	these two tumor suppressive processes	1815:1851	these two tumor suppressive processes	1815:1851	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	8	45	theme	GluIIβ	1563:1568	arg1	inhibition					1570:1579	GluIIβ inhibition	1563:1579	GluIIβ inhibition	1563:1579	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	6	46	dep	RESULTS	1088:1094	arg1	found					1099:1103	found	1099:1103	found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells	1099:1233	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	2	47	theme	glucosidase	304:314	arg1	GluIIβ					320:325	GluIIβ	320:325	GluIIβ	320:325	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	2	47	theme	glucosidase	304:314	arg1	subunit					293:299	the beta subunit	284:299	the beta subunit of glucosidase II (GluIIβ) levels	284:333	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	10	48	theme	blocking	1860:1867	arg1	autophagy					1869:1877	blocking autophagy	1860:1877	blocking autophagy by lysosomal inhibitors	1860:1901	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	8	49	theme	inhibition	1409:1418	arg1	p53-dependent					1435:1447	p53-dependent	1435:1447	p53-dependent	1435:1447	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	8	49	theme	inhibition	1409:1418	arg1	effect					1392:1397	the apoptosis inducing effect	1369:1397	the apoptosis inducing effect of GluIIβ inhibition	1369:1418	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	3	50	theme	GluIIβ	475:480	arg1	role					467:470	the role	463:470	the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells	463:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	4	51	used	used	743:746	arg2	technology					728:737	a siRNA-based technology	714:737	a siRNA-based technology	714:737	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	1	52	theme	post-translational	199:216	arg1	modification					218:229	the post-translational modification	195:229	the post-translational modification of N-linked glycoproteins	195:255	PURPOSE Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins.
28929344	1	53	theme	glycoproteins	243:255	arg1	modification					218:229	the post-translational modification	195:229	the post-translational modification of N-linked glycoproteins	195:255	PURPOSE Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins.
28929344	4	54	theme	p53	847:849	arg1	status					851:856	p53 status	847:856	p53 status	847:856	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	10	55	theme	bromoconduritol	1945:1959	arg1	effect					1935:1940	the apoptosis-inducing effect	1912:1940	the apoptosis-inducing effect of bromoconduritol	1912:1959	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	6	56	theme	wild-type	1215:1223	arg1	cells					1229:1233	only wild-type p53 cells	1210:1233	only wild-type p53 cells	1210:1233	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	1	57	link	N-linked	234:241	arg1	glycoproteins					243:255	N-linked glycoproteins	234:255	N-linked glycoproteins	234:255	PURPOSE Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins.
28929344	1	58	theme	PURPOSE	139:145	arg1	Glucosidase					147:157	PURPOSE Glucosidase II	139:160	PURPOSE Glucosidase II	139:160	PURPOSE Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins.
28929344	9	59	theme	tumor	1825:1829	arg1	processes					1843:1851	these two tumor suppressive processes	1815:1851	these two tumor suppressive processes	1815:1851	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	9	60	theme	GluIIβ	1658:1663	arg1	inhibition					1665:1674	GluIIβ inhibition	1658:1674	GluIIβ inhibition	1658:1674	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	2	61	theme	subunit	293:299	arg1	levels					328:333	the beta subunit of glucosidase II (GluIIβ) levels	284:333	the beta subunit of glucosidase II (GluIIβ) levels	284:333	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	4	62	theme	carcinoma	818:826	arg1	cells					828:832	lung carcinoma cells	813:832	lung carcinoma cells differing in p53 status	813:856	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	10	63	theme	p53	1977:1979	arg1	status					1981:1986	p53 status	1977:1986	p53 status	1977:1986	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	0	64	theme	carcinoma	96:104	arg1	cells					106:110	lung carcinoma cells	91:110	lung carcinoma cells	91:110	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	5	65	theme	Western	993:999	arg1	blotting					1001:1008	Western blotting	993:1008	Western blotting	993:1008	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	3	66	theme	lung	530:533	arg1	carcinoma-					535:544	lung carcinoma-	530:544	lung carcinoma-	530:544	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	3	67	theme	immortalized	550:561	arg1	cells					598:602	immortalized human bronchial epithelial-derived cells	550:602	immortalized human bronchial epithelial-derived cells	550:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	0	68	from	role	45:48	arg1	cells					106:110	lung carcinoma cells	91:110	lung carcinoma cells	91:110	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	0	68	from	role	45:48	arg1	autophagy					53:61	autophagy	53:61	autophagy	53:61	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	0	68	from	role	45:48	arg1	regulation					77:86	apoptosis regulation	67:86	apoptosis regulation	67:86	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	4	69	theme	selective	615:623	arg1	inhibitor					640:648	A selective glucosidase II inhibitor	613:648	A selective glucosidase II inhibitor	613:648	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	4	69	theme	selective	615:623	arg1	bromoconduritol					651:665	bromoconduritol	651:665	bromoconduritol	651:665	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	10	70	theme	combined	1995:2002	arg1	use					2004:2006	their combined use	1989:2006	their combined use	1989:2006	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	0	71	theme	p53-dependent	117:129	arg1	manner					131:136	a p53-dependent manner	115:136	a p53-dependent manner	115:136	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	5	72	theme	annexin	1046:1052	arg1	method					1080:1085	an annexin V-FITC/PI double labeling method	1043:1085	an annexin V-FITC/PI double labeling method	1043:1085	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	9	73	theme	lung	1714:1717	arg1	cells					1737:1741	lung carcinoma-derived cells	1714:1741	lung carcinoma-derived cells	1714:1741	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	7	74	theme	signaling	1340:1348	arg1	pathways					1350:1357	the EGFR/RTK and PI3K/AKT signaling pathways	1314:1357	pathways	1350:1357	We also found that GluIIβ inhibition dose-dependently decreased activation of the EGFR/RTK and PI3K/AKT signaling pathways.
28929344	4	75	theme	enzyme	694:699	arg1	activity					701:708	GluII enzyme activity	688:708	GluII enzyme activity	688:708	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	3	76	theme	bronchial	569:577	arg1	cells					598:602	immortalized human bronchial epithelial-derived cells	550:602	immortalized human bronchial epithelial-derived cells	550:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	8	77	theme	combined	1466:1473	arg1	treatment					1475:1483	a combined treatment	1464:1483	a combined treatment with lysosomal inhibitors to block autophagy	1464:1528	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	6	78	theme	autophagy	1157:1165	arg1	induction					1144:1152	the induction	1140:1152	the induction of autophagy in all cell lines tested	1140:1190	RESULTS We found that GluIIβ inhibition resulted in the induction of autophagy in all cell lines tested, but apoptosis in only wild-type p53 cells.
28929344	8	79	dep	p53	1599:1601	arg1	wild-type					1589:1597	wild-type	1589:1597	wild-type	1589:1597	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	0	80	theme	apoptosis	67:75	arg1	regulation					77:86	apoptosis regulation	67:86	apoptosis regulation	67:86	Glucosidase II beta subunit (GluIIβ) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner.
28929344	5	81	theme	double	1064:1069	arg1	method					1080:1085	an annexin V-FITC/PI double labeling method	1043:1085	an annexin V-FITC/PI double labeling method	1043:1085	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	8	82	theme	block	1514:1518	arg1	autophagy					1520:1528	block autophagy	1514:1528	block autophagy	1514:1528	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	8	83	with	treatment	1475:1483	arg1	inhibitors					1500:1509	lysosomal inhibitors	1490:1509	lysosomal inhibitors	1490:1509	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	3	84	link	epithelial-derived	579:596	arg1	cells					598:602	immortalized human bronchial epithelial-derived cells	550:602	immortalized human bronchial epithelial-derived cells	550:602	Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells.
28929344	9	85	dep	CONCLUSIONS	1623:1633	arg1	indicate					1644:1651	indicate	1644:1651	indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes	1644:1851	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	1	86	gly	glycoproteins	243:255	arg1	glycoproteins					243:255	N-linked glycoproteins	234:255	N-linked glycoproteins	234:255	PURPOSE Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins.
28929344	5	87	theme	cell	906:909	arg1	progression					917:927	cell cycle progression	906:927	cell cycle progression	906:927	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	8	88	theme	apoptotic	1543:1551	arg1	effect					1553:1558	the apoptotic effect	1539:1558	the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells	1539:1620	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	4	89	theme	siRNA-based	716:726	arg1	technology					728:737	a siRNA-based technology	714:737	a siRNA-based technology	714:737	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	4	90	theme	GluIIβ	782:787	arg1	expression					764:773	the expression	760:773	the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status	760:856	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	2	91	theme	carcinoma	371:379	arg1	tissues					381:387	lung carcinoma tissues	366:387	lung carcinoma tissues	366:387	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	9	92	link	carcinoma-derived	1719:1735	arg1	cells					1737:1741	lung carcinoma-derived cells	1714:1741	lung carcinoma-derived cells	1714:1741	CONCLUSIONS Our data indicate that GluIIβ inhibition results in autophagy and apoptosis in lung carcinoma-derived cells, supporting the hypothesis that this enzyme may play a role in blocking these two tumor suppressive processes.
28929344	2	93	theme	lung	421:424	arg1	tumorigenesis					426:438	lung tumorigenesis	421:438	lung tumorigenesis	421:438	Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis.
28929344	8	94	theme	inhibition	1570:1579	arg1	effect					1553:1558	the apoptotic effect	1539:1558	the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells	1539:1620	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	10	95	theme	lysosomal	1882:1890	arg1	inhibitors					1892:1901	lysosomal inhibitors	1882:1901	lysosomal inhibitors	1882:1901	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	4	96	theme	gene	798:801	arg1	PRKCSH					803:808	gene PRKCSH	798:808	gene PRKCSH in lung carcinoma cells differing in p53 status	798:856	METHODS A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status.
28929344	5	97	theme	flow	948:951	arg1	cytometry					953:961	flow cytometry	948:961	flow cytometry	948:961	Cell viability was assessed using a MTT assay, cell cycle progression was assessed using flow cytometry, autophagy was assessed using Western blotting and apoptosis was assessed using an annexin V-FITC/PI double labeling method.
28929344	10	98	theme	lung	2067:2070	arg1	cancer					2072:2077	lung cancer	2067:2077	particularly lung cancer	2054:2077	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	10	98	theme	lung	2067:2070	arg1	cancer					2046:2051	cancer	2046:2051	cancer	2046:2051	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	8	99	theme	apoptosis	1373:1381	arg1	p53-dependent					1435:1447	p53-dependent	1435:1447	p53-dependent	1435:1447	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	8	99	theme	apoptosis	1373:1381	arg1	effect					1392:1397	the apoptosis inducing effect	1369:1397	the apoptosis inducing effect of GluIIβ inhibition	1369:1418	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	8	100	theme	p53	1599:1601	arg1	cells					1616:1620	both wild-type p53 and p53-null cells	1584:1620	both wild-type p53 and p53-null cells	1584:1620	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
28929344	10	101	theme	apoptosis-inducing	1916:1933	arg1	effect					1935:1940	the apoptosis-inducing effect	1912:1940	the apoptosis-inducing effect of bromoconduritol	1912:1959	Since blocking autophagy by lysosomal inhibitors enhanced the apoptosis-inducing effect of bromoconduritol, independent of p53 status, their combined use may hold promise for the treatment of cancer, particularly lung cancer.
28929344	8	102	theme	GluIIβ	1402:1407	arg1	inhibition					1409:1418	GluIIβ inhibition	1402:1418	GluIIβ inhibition	1402:1418	Although the apoptosis inducing effect of GluIIβ inhibition appeared to be p53-dependent, we found that a combined treatment with lysosomal inhibitors to block autophagy enhanced the apoptotic effect of GluIIβ inhibition in both wild-type p53 and p53-null cells.
30885209	0	0	theme	lung	103:106	arg1	cancer					108:113	non-small cell lung cancer	88:113	non-small cell lung cancer	88:113	NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer.
30885209	1	1	from	de-differentiation	202:219	arg1	NSCLC					277:281	NSCLC	277:281	NSCLC	277:281	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	1	from	de-differentiation	202:219	arg1	cancer					269:274	non-small cell lung cancer	249:274	non-small cell lung cancer (NSCLC)	249:282	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	2	2	theme	metabolic	372:380	arg1	pathways					382:389	metabolic pathways	372:389	metabolic pathways that link EMT with cancer progression	372:427	While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed.
30885209	4	3	theme	diphosphate	622:632	arg1	N-acetylglucosamine					634:652	uridine diphosphate N-acetylglucosamine	614:652	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc)	614:665	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	4	3	theme	diphosphate	622:632	arg1	UDP-GlcNAc					655:664	UDP-GlcNAc	655:664	UDP-GlcNAc	655:664	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	0	4	theme	cell	98:101	arg1	cancer					108:113	non-small cell lung cancer	88:113	non-small cell lung cancer	88:113	NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer.
30885209	5	5	theme	O-linked	708:715	arg1	OGT					750:752	OGT	750:752	OGT	750:752	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	5	5	theme	O-linked	708:715	arg1	transferase					737:747	O-linked N-acetylglucosamine transferase	708:747	O-linked N-acetylglucosamine transferase (OGT)	708:753	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	6	6	theme	mesenchymal	885:895	arg1	NSCLC					897:901	mesenchymal NSCLC	885:901	mesenchymal NSCLC	885:901	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	4	7	theme	uridine	614:620	arg1	N-acetylglucosamine					634:652	uridine diphosphate N-acetylglucosamine	614:652	uridine diphosphate N-acetylglucosamine (UDP-GlcNAc)	614:665	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	4	7	theme	uridine	614:620	arg1	UDP-GlcNAc					655:664	UDP-GlcNAc	655:664	UDP-GlcNAc	655:664	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	11	8	theme	activity	1524:1531	arg1	Modulation					1504:1513	Modulation	1504:1513	Modulation of GFPT2 activity	1504:1531	Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.
30885209	9	9	dep	cell	1313:1316	arg1	migration					1318:1326	migration	1318:1326	migration	1318:1326	Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT.
30885209	5	10	theme	N-acetylglucosamine	717:735	arg1	OGT					750:752	OGT	750:752	OGT	750:752	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	5	10	theme	N-acetylglucosamine	717:735	arg1	transferase					737:747	O-linked N-acetylglucosamine transferase	708:747	O-linked N-acetylglucosamine transferase (OGT)	708:753	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	7	11	theme	metabolic	1013:1021	arg1	enzyme					1023:1028	this metabolic enzyme	1008:1028	this metabolic enzyme	1008:1028	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	6	12	theme	transcriptomic	780:793	arg1	data					795:798	our transcriptomic data	776:798	our transcriptomic data	776:798	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	0	13	from	migration	75:83	arg1	cancer					108:113	non-small cell lung cancer	88:113	non-small cell lung cancer	88:113	NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer.
30885209	5	14	theme	transferase	737:747	arg1	activator					695:703	the obligate activator	682:703	the obligate activator of O-linked N-acetylglucosamine transferase (OGT)	682:753	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	5	14	theme	transferase	737:747	arg1	UDP-GlcNAc					668:677	UDP-GlcNAc	668:677	UDP-GlcNAc	668:677	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	6	15	theme	genes	876:880	arg1	genes					876:880	the most significantly upregulated metabolic genes	831:880	the most significantly upregulated metabolic genes in mesenchymal NSCLC	831:901	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	6	15	theme	genes	876:880	arg1	one					824:826	one	824:826	one	824:826	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	9	16	from	NSCLC	1267:1271	arg1	Depletion					1234:1242	Depletion	1234:1242	Depletion of GFPT2 expression in NSCLC	1234:1271	Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT.
30885209	11	17	theme	important	1554:1562	arg1	target					1576:1581	a potentially important therapeutic target	1540:1581	a potentially important therapeutic target to combat NSCLC disease progression	1540:1617	Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.
30885209	4	18	theme	N-acetylglucosamine	634:652	arg1	synthesis					601:609	the synthesis	597:609	the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc)	597:665	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	6	19	theme	metabolic	866:874	arg1	genes					876:880	the most significantly upregulated metabolic genes	831:880	the most significantly upregulated metabolic genes in mesenchymal NSCLC	831:901	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	10	20	theme	cancer	1397:1402	arg1	progression					1404:1414	cancer progression	1397:1414	cancer progression	1397:1414	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	2	21	theme	cancer	410:415	arg1	progression					417:427	cancer progression	410:427	cancer progression	410:427	While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed.
30885209	11	22	theme	GFPT2	1518:1522	arg1	activity					1524:1531	GFPT2 activity	1518:1531	GFPT2 activity	1518:1531	Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.
30885209	7	23	theme	invasion	1086:1093	arg1	processes					1055:1063	EMT-driven processes	1044:1063	EMT-driven processes of cell motility and invasion	1044:1093	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	6	24	theme	upregulated	854:864	arg1	genes					876:880	the most significantly upregulated metabolic genes	831:880	the most significantly upregulated metabolic genes in mesenchymal NSCLC	831:901	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	7	25	theme	cell	1068:1071	arg1	motility					1073:1080	cell motility	1068:1080	cell motility	1068:1080	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	10	26	dep	Consistent	1365:1374	arg1	CONCLUSIONS					1353:1363	CONCLUSIONS	1353:1363	CONCLUSIONS	1353:1363	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	5	27	theme	obligate	686:693	arg1	activator					695:703	the obligate activator	682:703	the obligate activator of O-linked N-acetylglucosamine transferase (OGT)	682:753	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	5	27	theme	obligate	686:693	arg1	UDP-GlcNAc					668:677	UDP-GlcNAc	668:677	UDP-GlcNAc	668:677	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	9	28	from	expression	1253:1262	arg1	NSCLC					1267:1271	NSCLC	1267:1271	NSCLC	1267:1271	Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT.
30885209	2	29	theme	altered	326:332	arg1	utilization					341:351	altered energy utilization	326:351	altered energy utilization	326:351	While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed.
30885209	6	30	theme	METHODS	756:762	arg1	Analysis					764:771	METHODS Analysis	756:771	METHODS Analysis of our transcriptomic data	756:798	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	10	31	theme	clinical	1477:1484	arg1	outcome					1486:1492	poor clinical outcome	1472:1492	poor clinical outcome in NSCLC	1472:1501	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	7	32	theme	Ectopic	904:910	arg1	expression					918:927	Ectopic GFPT2 expression	904:927	Ectopic GFPT2 expression	904:927	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	8	33	theme	RESULTS	1096:1102	arg1	work					1108:1111	RESULTS Our work	1096:1111	RESULTS Our work	1096:1111	RESULTS Our work demonstrates that GFPT2 is transcriptionally upregulated by NF-κB and repressed by the NAD+-dependent deacetylase SIRT6.
30885209	7	34	theme	gene	941:944	arg1	strategies					956:965	gene silencing strategies	941:965	gene silencing strategies	941:965	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	11	35	theme	NSCLC	1593:1597	arg1	progression					1607:1617	NSCLC disease progression	1593:1617	NSCLC disease progression	1593:1617	Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.
30885209	7	36	theme	enzyme	1023:1028	arg1	importance					994:1003	the importance	990:1003	the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion	990:1093	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	1	37	theme	BACKGROUND	116:125	arg1	EMT					165:167	EMT	165:167	EMT	165:167	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	37	theme	BACKGROUND	116:125	arg1	transition					153:162	BACKGROUND Epithelial-to-mesenchymal transition	116:162	BACKGROUND Epithelial-to-mesenchymal transition (EMT)	116:168	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	7	38	theme	GFPT2	912:916	arg1	expression					918:927	Ectopic GFPT2 expression	904:927	Ectopic GFPT2 expression	904:927	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	10	39	theme	poor	1472:1475	arg1	outcome					1486:1492	poor clinical outcome	1472:1492	poor clinical outcome in NSCLC	1472:1501	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	0	40	theme	glutamine-fructose-6-phosphate	18:47	arg1	transaminase					49:60	glutamine-fructose-6-phosphate transaminase 2	18:62	glutamine-fructose-6-phosphate transaminase 2	18:62	NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer.
30885209	10	41	theme	GFPT2	1439:1443	arg1	expression					1445:1454	elevated GFPT2 expression	1430:1454	elevated GFPT2 expression	1430:1454	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	1	42	theme	Epithelial-to-mesenchymal	127:151	arg1	EMT					165:167	EMT	165:167	EMT	165:167	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	42	theme	Epithelial-to-mesenchymal	127:151	arg1	transition					153:162	BACKGROUND Epithelial-to-mesenchymal transition	116:162	BACKGROUND Epithelial-to-mesenchymal transition (EMT)	116:168	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	9	43	from	Depletion	1234:1242	arg1	NSCLC					1267:1271	NSCLC	1267:1271	NSCLC	1267:1271	Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT.
30885209	4	44	from	enzyme	587:592	arg1	synthesis					601:609	the synthesis	597:609	the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc)	597:665	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	11	45	theme	therapeutic	1564:1574	arg1	target					1576:1581	a potentially important therapeutic target	1540:1581	a potentially important therapeutic target to combat NSCLC disease progression	1540:1617	Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.
30885209	10	46	from	outcome	1486:1492	arg1	NSCLC					1497:1501	NSCLC	1497:1501	NSCLC	1497:1501	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	6	47	from	genes	876:880	arg1	NSCLC					897:901	mesenchymal NSCLC	885:901	mesenchymal NSCLC	885:901	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	1	48	from	invasion	237:244	arg1	NSCLC					277:281	NSCLC	277:281	NSCLC	277:281	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	48	from	invasion	237:244	arg1	cancer					269:274	non-small cell lung cancer	249:274	non-small cell lung cancer (NSCLC)	249:282	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	3	49	theme	mesenchymal	475:485	arg1	NSCLC					487:491	mesenchymal NSCLC	475:491	mesenchymal NSCLC	475:491	Work presented here indicates that mesenchymal NSCLC upregulates glutamine-fructose-6-phosphate transaminase 2 (GFPT2).
30885209	7	50	theme	motility	1073:1080	arg1	processes					1055:1063	EMT-driven processes	1044:1063	EMT-driven processes of cell motility and invasion	1044:1093	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	4	51	theme	rate-limiting	573:585	arg1	enzyme					587:592	the rate-limiting enzyme	569:592	the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc)	569:665	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	4	51	theme	rate-limiting	573:585	arg1	GFPT2					560:564	GFPT2	560:564	GFPT2	560:564	GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc).
30885209	8	52	theme	NAD+-dependent	1200:1213	arg1	SIRT6					1227:1231	the NAD+-dependent deacetylase SIRT6	1196:1231	the NAD+-dependent deacetylase SIRT6	1196:1231	RESULTS Our work demonstrates that GFPT2 is transcriptionally upregulated by NF-κB and repressed by the NAD+-dependent deacetylase SIRT6.
30885209	10	53	theme	elevated	1430:1437	arg1	expression					1445:1454	elevated GFPT2 expression	1430:1454	elevated GFPT2 expression	1430:1454	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	3	54	theme	glutamine-fructose-6-phosphate	505:534	arg1	transaminase					536:547	glutamine-fructose-6-phosphate transaminase 2	505:549	glutamine-fructose-6-phosphate transaminase 2 (GFPT2)	505:557	Work presented here indicates that mesenchymal NSCLC upregulates glutamine-fructose-6-phosphate transaminase 2 (GFPT2).
30885209	3	54	theme	glutamine-fructose-6-phosphate	505:534	arg1	GFPT2					552:556	GFPT2	552:556	GFPT2	552:556	Work presented here indicates that mesenchymal NSCLC upregulates glutamine-fructose-6-phosphate transaminase 2 (GFPT2).
30885209	7	55	theme	EMT-driven	1044:1053	arg1	processes					1055:1063	EMT-driven processes	1044:1063	EMT-driven processes of cell motility and invasion	1044:1093	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	1	56	theme	non-small	249:257	arg1	NSCLC					277:281	NSCLC	277:281	NSCLC	277:281	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	56	theme	non-small	249:257	arg1	cancer					269:274	non-small cell lung cancer	249:274	non-small cell lung cancer (NSCLC)	249:282	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	10	57	with	Consistent	1365:1374	arg1	GFPT2					1381:1385	GFPT2	1381:1385	GFPT2 promoting cancer progression	1381:1414	CONCLUSIONS Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC.
30885209	9	58	theme	GFPT2	1247:1251	arg1	expression					1253:1262	GFPT2 expression	1247:1262	GFPT2 expression in NSCLC	1247:1271	Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT.
30885209	7	59	used	used	972:975	arg2	strategies					956:965	gene silencing strategies	941:965	gene silencing strategies	941:965	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	7	59	used	used	972:975	arg2	expression					918:927	Ectopic GFPT2 expression	904:927	Ectopic GFPT2 expression	904:927	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	2	60	theme	energy	334:339	arg1	utilization					341:351	altered energy utilization	326:351	altered energy utilization	326:351	While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed.
30885209	11	61	theme	disease	1599:1605	arg1	progression					1607:1617	NSCLC disease progression	1593:1617	NSCLC disease progression	1593:1617	Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.
30885209	1	62	theme	cell	259:262	arg1	NSCLC					277:281	NSCLC	277:281	NSCLC	277:281	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	62	theme	cell	259:262	arg1	cancer					269:274	non-small cell lung cancer	249:274	non-small cell lung cancer (NSCLC)	249:282	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	0	63	theme	non-small	88:96	arg1	cancer					108:113	non-small cell lung cancer	88:113	non-small cell lung cancer	88:113	NF-κB upregulates glutamine-fructose-6-phosphate transaminase 2 to promote migration in non-small cell lung cancer.
30885209	5	64	link	O-linked	708:715	arg1	OGT					750:752	OGT	750:752	OGT	750:752	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	5	64	link	O-linked	708:715	arg1	transferase					737:747	O-linked N-acetylglucosamine transferase	708:747	O-linked N-acetylglucosamine transferase (OGT)	708:753	UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT).
30885209	1	65	from	migration	222:230	arg1	NSCLC					277:281	NSCLC	277:281	NSCLC	277:281	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	65	from	migration	222:230	arg1	cancer					269:274	non-small cell lung cancer	249:274	non-small cell lung cancer (NSCLC)	249:282	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	66	theme	lung	264:267	arg1	NSCLC					277:281	NSCLC	277:281	NSCLC	277:281	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	1	66	theme	lung	264:267	arg1	cancer					269:274	non-small cell lung cancer	249:274	non-small cell lung cancer (NSCLC)	249:282	BACKGROUND Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC).
30885209	8	67	theme	deacetylase	1215:1225	arg1	SIRT6					1227:1231	the NAD+-dependent deacetylase SIRT6	1196:1231	the NAD+-dependent deacetylase SIRT6	1196:1231	RESULTS Our work demonstrates that GFPT2 is transcriptionally upregulated by NF-κB and repressed by the NAD+-dependent deacetylase SIRT6.
30885209	6	68	theme	data	795:798	arg1	Analysis					764:771	METHODS Analysis	756:771	METHODS Analysis of our transcriptomic data	756:798	METHODS Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC.
30885209	2	69	theme	pathways	382:389	arg1	identification					354:367	identification	354:367	identification of metabolic pathways that link EMT with cancer progression	354:427	While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed.
30885209	7	70	theme	silencing	946:954	arg1	strategies					956:965	gene silencing strategies	941:965	gene silencing strategies	941:965	Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion.
30885209	9	71	theme	expression	1253:1262	arg1	Depletion					1234:1242	Depletion	1234:1242	Depletion of GFPT2 expression in NSCLC	1234:1271	Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT.
29533936	10	0	theme	higher	1543:1548	arg1	levels					1550:1555	higher levels	1543:1555	higher levels of DR5	1543:1562	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	10	1	theme	apoptosis-initiating	1720:1739	arg1	caspase-8					1750:1758	the apoptosis-initiating protease caspase-8	1716:1758	the apoptosis-initiating protease caspase-8 to form DISC	1716:1771	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	5	2	theme	NSCLC	707:711	arg1	samples					722:728	Thirty NSCLC clinical samples	700:728	Thirty NSCLC clinical samples	700:728	Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
29533936	9	3	theme	expression	1387:1396	arg1	levels					1398:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29533936	7	4	theme	DR	1175:1176	arg1	localization					1159:1170	the localization	1155:1170	the localization of DR	1155:1176	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	7	5	theme	sulfate-polyacrylamide	1068:1089	arg1	electrophoresis					1095:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	10	6	theme	DR5	1560:1562	arg1	levels					1550:1555	higher levels	1543:1555	higher levels of DR5	1543:1562	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	10	7	dep	RESULTS	1490:1496	arg1	found					1501:1505	found	1501:1505	found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis	1501:1796	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	6	8	theme	DR	834:835	arg1	expression					837:846	DR expression	834:846	DR expression	834:846	After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting.
29533936	3	9	with	combination	504:514	arg1	TRAIL					521:525	TRAIL	521:525	TRAIL	521:525	Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL.
29533936	2	10	theme	cancer	308:313	arg1	cells					323:327	many human non-small cell lung cancer (NSCLC) cells	277:327	many human non-small cell lung cancer (NSCLC) cells	277:327	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	10	11	theme	DR5	1659:1661	arg1	accumulation					1663:1674	DR5 accumulation	1659:1674	DR5 accumulation	1659:1674	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	0	12	theme	Death	106:110	arg1	Receptor					112:119	Death Receptor 5	106:121	Death Receptor 5	106:121	N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.
29533936	12	13	theme	cancer	1963:1968	arg1	cells					1970:1974	cancer cells	1963:1974	cancer cells	1963:1974	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	2	14	theme	lung	303:306	arg1	NSCLC					316:320	NSCLC	316:320	NSCLC	316:320	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	2	14	theme	lung	303:306	arg1	cancer					308:313	non-small cell lung cancer	288:313	many human non-small cell lung cancer (NSCLC) cells	277:327	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	9	15	theme	RNA	1453:1455	arg1	interference					1457:1468	RNA interference	1453:1468	RNA interference	1453:1468	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29533936	3	16	theme	agents	483:488	arg1	development					441:451	the development	437:451	the development of novel adjuvant therapeutic agents	437:488	Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL.
29533936	12	17	theme	TRAIL-mediated	2053:2066	arg1	therapy					2083:2089	TRAIL-mediated NSCLC-targeted therapy	2053:2089	TRAIL-mediated NSCLC-targeted therapy	2053:2089	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	12	18	theme	novel	2027:2031	arg1	agent					2043:2047	a novel effective agent	2025:2047	a novel effective agent for TRAIL-mediated NSCLC-targeted therapy	2025:2089	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	5	19	used	used	735:738	arg2	samples					722:728	Thirty NSCLC clinical samples	700:728	Thirty NSCLC clinical samples	700:728	Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
29533936	2	20	theme	cell	298:301	arg1	NSCLC					316:320	NSCLC	316:320	NSCLC	316:320	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	2	20	theme	cell	298:301	arg1	cancer					308:313	non-small cell lung cancer	288:313	many human non-small cell lung cancer (NSCLC) cells	277:327	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	5	21	theme	5	794:794	arg1	expression					754:763	the expression	750:763	the expression of death receptor (DR) 4 and 5	750:794	Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
29533936	4	22	theme	N-acetyl-glucosamine	565:584	arg1	effect					555:560	the effect	551:560	the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL	551:662	METHODS In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo.
29533936	7	23	theme	DR.	1036:1038	arg1	GlcNAc					1003:1008	GlcNAc	1003:1008	GlcNAc	1003:1008	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	7	23	theme	DR.	1036:1038	arg1	rate					1028:1031	the metabolic rate	1014:1031	the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering	1014:1148	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	9	24	link	O-linked	1371:1378	arg1	levels					1398:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29533936	2	25	theme	non-small	288:296	arg1	NSCLC					316:320	NSCLC	316:320	NSCLC	316:320	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	2	25	theme	non-small	288:296	arg1	cancer					308:313	non-small cell lung cancer	288:313	many human non-small cell lung cancer (NSCLC) cells	277:327	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	6	26	dep	GlcNAc	803:808	arg1	co-treatment					820:831	co-treatment	820:831	co-treatment	820:831	After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting.
29533936	7	27	theme	receptor	1130:1137	arg1	clustering					1139:1148	receptor clustering	1130:1148	receptor clustering	1130:1148	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	7	28	theme	metabolic	1018:1026	arg1	rate					1028:1031	the metabolic rate	1014:1031	the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering	1014:1148	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	12	29	dep	CONCLUSION	1877:1886	arg1	uncovered					1902:1910	uncovered	1902:1910	uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy	1902:2089	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	8	30	theme	complex	1355:1361	arg1	formation					1317:1325	the formation	1313:1325	the formation of death-inducing signaling complex (DISC)	1313:1368	Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC).
29533936	10	31	theme	GlcNAc	1578:1583	arg1	co-treatment					1585:1596	GlcNAc co-treatment	1578:1596	GlcNAc co-treatment	1578:1596	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	2	32	theme	clinical	384:391	arg1	application					393:403	its clinical application	380:403	its clinical application	380:403	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	5	33	theme	death	768:772	arg1	DR					784:785	DR	784:785	DR	784:785	Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
29533936	5	33	theme	death	768:772	arg1	receptor					774:781	death receptor	768:781	death receptor (DR)	768:786	Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
29533936	10	34	theme	clinical	1516:1523	arg1	samples					1525:1531	the clinical samples	1512:1531	the clinical samples	1512:1531	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	8	35	theme	signaling	1345:1353	arg1	complex					1355:1361	death-inducing signaling complex	1330:1361	death-inducing signaling complex (DISC)	1330:1368	Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC).
29533936	8	35	theme	signaling	1345:1353	arg1	DISC					1364:1367	DISC	1364:1367	DISC	1364:1367	Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC).
29533936	1	36	theme	potential	209:217	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	36	theme	potential	209:217	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	0	37	theme	Cell	42:45	arg1	Cells					59:63	Non-Small Cell Lung Cancer Cells	32:63	Non-Small Cell Lung Cancer Cells	32:63	N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.
29533936	8	38	theme	co-immunoprecipitation	1259:1280	arg1	assay					1282:1286	a co-immunoprecipitation assay	1257:1286	a co-immunoprecipitation assay	1257:1286	Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC).
29533936	1	39	theme	anti-cancer	219:229	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	39	theme	anti-cancer	219:229	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	0	40	theme	Non-Small	32:40	arg1	Cells					59:63	Non-Small Cell Lung Cancer Cells	32:63	Non-Small Cell Lung Cancer Cells	32:63	N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.
29533936	8	41	theme	death-inducing	1330:1343	arg1	complex					1355:1361	death-inducing signaling complex	1330:1361	death-inducing signaling complex (DISC)	1330:1368	Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC).
29533936	8	41	theme	death-inducing	1330:1343	arg1	DISC					1364:1367	DISC	1364:1367	DISC	1364:1367	Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC).
29533936	12	42	theme	TRAIL-induced	1979:1991	arg1	apoptosis					1993:2001	TRAIL-induced apoptosis	1979:2001	TRAIL-induced apoptosis	1979:2001	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	12	43	theme	effective	2033:2041	arg1	agent					2043:2047	a novel effective agent	2025:2047	a novel effective agent for TRAIL-mediated NSCLC-targeted therapy	2025:2089	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	3	44	theme	adjuvant	462:469	arg1	agents					483:488	novel adjuvant therapeutic agents	456:488	novel adjuvant therapeutic agents	456:488	Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL.
29533936	0	45	theme	Cancer	52:57	arg1	Cells					59:63	Non-Small Cell Lung Cancer Cells	32:63	Non-Small Cell Lung Cancer Cells	32:63	N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.
29533936	6	46	theme	western	884:890	arg1	blotting					892:899	western blotting	884:899	western blotting	884:899	After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting.
29533936	9	47	theme	mediated	1470:1477	arg1	knockdown					1479:1487	mediated knockdown	1470:1487	mediated knockdown	1470:1487	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29533936	9	48	dep	overexpression	1434:1447	arg1	knockdown					1479:1487	mediated knockdown	1470:1487	mediated knockdown	1470:1487	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29533936	10	49	theme	apoptosis	1635:1643	arg1	effect					1611:1616	the effect	1607:1616	the effect of TRAIL-induced apoptosis	1607:1643	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	1	50	theme	due	237:239	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	50	theme	due	237:239	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	0	51	theme	Lung	47:50	arg1	Cells					59:63	Non-Small Cell Lung Cancer Cells	32:63	Non-Small Cell Lung Cancer Cells	32:63	N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.
29533936	5	52	theme	receptor	774:781	arg1	expression					754:763	the expression	750:763	the expression of death receptor (DR) 4 and 5	750:794	Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
29533936	4	53	theme	monosaccharide	606:619	arg1	N-acetyl-glucosamine					565:584	N-acetyl-glucosamine	565:584	N-acetyl-glucosamine (GlcNAc)	565:593	METHODS In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo.
29533936	4	53	theme	monosaccharide	606:619	arg1	type					598:601	a type	596:601	a type of monosaccharide derived from chitosan	596:641	METHODS In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo.
29533936	7	54	theme	gel	1091:1093	arg1	electrophoresis					1095:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	12	55	theme	NSCLC-targeted	2068:2081	arg1	therapy					2083:2089	TRAIL-mediated NSCLC-targeted therapy	2053:2089	TRAIL-mediated NSCLC-targeted therapy	2053:2089	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	1	56	theme	BACKGROUND/AIMS	124:138	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	56	theme	BACKGROUND/AIMS	124:138	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	56	theme	BACKGROUND/AIMS	124:138	arg1	TRAIL					197:201	TRAIL	197:201	TRAIL	197:201	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	7	57	dep	DR.	1036:1038	arg1	used					1115:1118	used	1115:1118	was used to detect receptor clustering	1111:1148	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	6	58	theme	real-time	866:874	arg1	PCR					876:878	real-time PCR	866:878	real-time PCR	866:878	After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting.
29533936	3	59	theme	therapeutic	471:481	arg1	agents					483:488	novel adjuvant therapeutic agents	456:488	novel adjuvant therapeutic agents	456:488	Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL.
29533936	12	60	theme	molecular	1916:1924	arg1	mechanism					1926:1934	the molecular mechanism	1912:1934	the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy	1912:2089	CONCLUSION These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.
29533936	1	61	theme	Tumor	140:144	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	61	theme	Tumor	140:144	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	61	theme	Tumor	140:144	arg1	TRAIL					197:201	TRAIL	197:201	TRAIL	197:201	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	10	62	theme	TRAIL-induced	1621:1633	arg1	apoptosis					1635:1643	TRAIL-induced apoptosis	1621:1643	TRAIL-induced apoptosis	1621:1643	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	7	63	used	used	1115:1118	arg2	electrophoresis					1095:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	2	64	theme	human	282:286	arg1	cells					323:327	many human non-small cell lung cancer (NSCLC) cells	277:327	many human non-small cell lung cancer (NSCLC) cells	277:327	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	7	65	theme	protein	939:945	arg1	half-life					947:955	the protein half-life	935:955	the protein half-life	935:955	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	1	66	theme	necrosis	146:153	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	66	theme	necrosis	146:153	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	66	theme	necrosis	146:153	arg1	TRAIL					197:201	TRAIL	197:201	TRAIL	197:201	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	2	67	theme	many	277:280	arg1	cells					323:327	many human non-small cell lung cancer (NSCLC) cells	277:327	many human non-small cell lung cancer (NSCLC) cells	277:327	However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application.
29533936	7	68	theme	Non-reducing	1040:1051	arg1	electrophoresis					1095:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis	1040:1109	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	1	69	theme	factor-related	155:168	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	69	theme	factor-related	155:168	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	69	theme	factor-related	155:168	arg1	TRAIL					197:201	TRAIL	197:201	TRAIL	197:201	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	11	70	theme	DR5	1828:1830	arg1	clustering					1832:1841	DR5 clustering	1828:1841	DR5 clustering	1828:1841	Furthermore, GlcNAc promoted DR5 clustering by improving its O-glycosylation.
29533936	1	71	theme	selective	248:256	arg1	toxicity					258:265	its selective toxicity	244:265	its selective toxicity	244:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	5	72	theme	clinical	713:720	arg1	samples					722:728	Thirty NSCLC clinical samples	700:728	Thirty NSCLC clinical samples	700:728	Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5.
29533936	4	73	attach	derived	621:627	arg1	chitosan					634:641	chitosan	634:641	chitosan	634:641	METHODS In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo.
29533936	4	73	attach	derived	621:627	arg2	monosaccharide					606:619	monosaccharide	606:619	monosaccharide derived from chitosan	606:641	METHODS In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo.
29533936	3	74	theme	novel	456:460	arg1	agents					483:488	novel adjuvant therapeutic agents	456:488	novel adjuvant therapeutic agents	456:488	Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL.
29533936	1	75	theme	apoptosis-inducing	170:187	arg1	agent					231:235	a potential anti-cancer agent	207:235	a potential anti-cancer agent due to its selective toxicity	207:265	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	75	theme	apoptosis-inducing	170:187	arg1	ligand					189:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand	124:194	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)	124:202	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	1	75	theme	apoptosis-inducing	170:187	arg1	TRAIL					197:201	TRAIL	197:201	TRAIL	197:201	BACKGROUND/AIMS Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity.
29533936	9	76	theme	DR5	1430:1432	arg1	overexpression					1434:1447	DR5 overexpression	1430:1447	DR5 overexpression	1430:1447	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29533936	9	77	theme	O-linked	1371:1378	arg1	levels					1398:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29533936	0	78	theme	TRAIL-Induced	68:80	arg1	Apoptosis					82:90	TRAIL-Induced Apoptosis	68:90	TRAIL-Induced Apoptosis	68:90	N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.
29533936	7	79	theme	confocal	1223:1230	arg1	microscope					1232:1241	a confocal microscope	1221:1241	a confocal microscope	1221:1241	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	10	80	theme	protease	1741:1748	arg1	caspase-8					1750:1758	the apoptosis-initiating protease caspase-8	1716:1758	the apoptosis-initiating protease caspase-8 to form DISC	1716:1771	RESULTS We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis.
29533936	7	81	used	used	920:923	arg2	Cycloheximide					902:914	Cycloheximide	902:914	Cycloheximide	902:914	Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope.
29533936	9	82	theme	glycan	1380:1385	arg1	levels					1398:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels	1371:1403	O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown.
29315243	5	0	theme	transferase	880:890	arg1	overexpression					898:911	O-GlcNAc transferase (OGT) overexpression	871:911	O-GlcNAc transferase (OGT) overexpression	871:911	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	4	1	theme	osteogenic	597:606	arg1	differentiation					608:622	osteogenic differentiation	597:622	osteogenic differentiation	597:622	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	4	2	theme	bone	688:691	arg1	protein					707:713	recombinant human bone morphogenetic protein 2	670:715	recombinant human bone morphogenetic protein 2 (BMP2)	670:722	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	4	2	theme	bone	688:691	arg1	BMP2					718:721	BMP2	718:721	BMP2	718:721	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	0	3	theme	Cells	103:107	arg1	Differentiation					78:92	BMP2-Induced Osteogenic Differentiation	54:92	BMP2-Induced Osteogenic Differentiation of C2C12 Cells	54:107	Conditions Inducing Excessive O-GlcNAcylation Inhibit BMP2-Induced Osteogenic Differentiation of C2C12 Cells.
29315243	4	4	theme	C2C12	625:629	arg1	cells					631:635	C2C12 cells	625:635	C2C12 cells	625:635	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	6	5	theme	O-GlcNAcylation	928:942	arg1	effect					918:923	The effect	914:923	The effect of O-GlcNAcylation on osteoblast differentiation	914:972	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	8	6	theme	O-GlcNAcylation	1638:1652	arg1	levels					1654:1659	protein O-GlcNAcylation levels	1630:1659	protein O-GlcNAcylation levels	1630:1659	These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β-N-acetylglucosaminidase.
29315243	4	7	theme	human	682:686	arg1	protein					707:713	recombinant human bone morphogenetic protein 2	670:715	recombinant human bone morphogenetic protein 2 (BMP2)	670:722	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	4	7	theme	human	682:686	arg1	BMP2					718:721	BMP2	718:721	BMP2	718:721	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	3	8	theme	aberrant	412:419	arg1	increase					421:428	the aberrant increase	408:428	the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	408:502	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	6	9	theme	osteogenic	1031:1040	arg1	mRNAs					1054:1058	osteogenic marker gene mRNAs	1031:1058	osteogenic marker gene mRNAs	1031:1058	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	9	10	theme	high	1822:1825	arg1	differentiation					1857:1871	high glucose-suppressed osteogenic differentiation	1822:1871	high glucose-suppressed osteogenic differentiation	1822:1871	Our findings suggest that excessive protein O-GlcNAcylation contributes to high glucose-suppressed osteogenic differentiation.
29315243	9	11	theme	osteogenic	1846:1855	arg1	differentiation					1857:1871	high glucose-suppressed osteogenic differentiation	1822:1871	high glucose-suppressed osteogenic differentiation	1822:1871	Our findings suggest that excessive protein O-GlcNAcylation contributes to high glucose-suppressed osteogenic differentiation.
29315243	8	12	theme	protein	1630:1636	arg1	levels					1654:1659	protein O-GlcNAcylation levels	1630:1659	protein O-GlcNAcylation levels	1630:1659	These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β-N-acetylglucosaminidase.
29315243	4	13	theme	protein	707:713	arg1	presence					658:665	the presence	654:665	the presence of recombinant human bone morphogenetic protein 2 (BMP2)	654:722	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	5	14	theme	N-acetylglucosamine	830:848	arg1	concentrations					850:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	9	15	theme	glucose-suppressed	1827:1844	arg1	differentiation					1857:1871	high glucose-suppressed osteogenic differentiation	1822:1871	high glucose-suppressed osteogenic differentiation	1822:1871	Our findings suggest that excessive protein O-GlcNAcylation contributes to high glucose-suppressed osteogenic differentiation.
29315243	7	16	theme	alkaline	1558:1565	arg1	phosphatase					1567:1577	alkaline phosphatase	1558:1577	alkaline phosphatase	1558:1577	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	4	17	theme	morphogenetic	693:705	arg1	protein					707:713	recombinant human bone morphogenetic protein 2	670:715	recombinant human bone morphogenetic protein 2 (BMP2)	670:722	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	4	17	theme	morphogenetic	693:705	arg1	BMP2					718:721	BMP2	718:721	BMP2	718:721	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	7	18	with	treatment	1222:1230	arg1	glucosamine					1251:1261	glucosamine	1251:1261	glucosamine	1251:1261	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	18	with	treatment	1222:1230	arg1	glucose					1242:1248	high glucose	1237:1248	high glucose	1237:1248	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	18	with	treatment	1222:1230	arg1	N-acetylglucosamine					1266:1284	N-acetylglucosamine	1266:1284	N-acetylglucosamine	1266:1284	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	19	theme	high	1237:1240	arg1	glucose					1242:1248	high glucose	1237:1248	high glucose	1237:1248	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	6	20	from	effect	918:923	arg1	differentiation					958:972	osteoblast differentiation	947:972	osteoblast differentiation	947:972	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	7	21	theme	O-GlcNAcylated	1345:1358	arg1	proteins					1360:1367	O-GlcNAcylated proteins	1345:1367	O-GlcNAcylated proteins	1345:1367	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	6	22	theme	expression	1010:1019	arg1	levels					1021:1026	the expression levels	1006:1026	the expression levels of osteogenic marker gene mRNAs	1006:1058	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	5	23	theme	Excessive	725:733	arg1	O-GlcNAcylation					743:757	Excessive protein O-GlcNAcylation	725:757	Excessive protein O-GlcNAcylation	725:757	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	3	24	theme	O-linked-β-N-acetylglucosamine	441:470	arg1	O-GlcNAcylation					487:501	O-GlcNAcylation	487:501	O-GlcNAcylation	487:501	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	3	24	theme	O-linked-β-N-acetylglucosamine	441:470	arg1	glycosylation					472:484	protein O-linked-β-N-acetylglucosamine glycosylation	433:484	protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	433:502	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	5	25	theme	protein	735:741	arg1	O-GlcNAcylation					743:757	Excessive protein O-GlcNAcylation	725:757	Excessive protein O-GlcNAcylation	725:757	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	8	26	theme	OGT	1684:1686	arg1	inhibitor					1688:1696	an OGT inhibitor	1681:1696	an OGT inhibitor	1681:1696	These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β-N-acetylglucosaminidase.
29315243	8	26	theme	OGT	1684:1686	arg1	STO45849					1671:1678	STO45849	1671:1678	STO45849	1671:1678	These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β-N-acetylglucosaminidase.
29315243	1	27	theme	Hyperglycemic	110:122	arg1	conditions					124:133	Hyperglycemic conditions	110:133	Hyperglycemic conditions in diabetic patients	110:154	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	7	28	theme	total	1329:1333	arg1	levels					1335:1340	the total levels	1325:1340	the total levels of O-GlcNAcylated proteins	1325:1367	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	29	theme	marker	1468:1473	arg1	genes					1475:1479	osteogenic marker genes	1457:1479	osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1457:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	29	theme	marker	1468:1473	arg1	osterix					1489:1495	osterix	1489:1495	osterix	1489:1495	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	29	theme	marker	1468:1473	arg1	collagen					1531:1538	type I collagen	1524:1538	type I collagen	1524:1538	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	29	theme	marker	1468:1473	arg1	phosphatase					1507:1517	alkaline phosphatase	1498:1517	alkaline phosphatase	1498:1517	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	29	theme	marker	1468:1473	arg1	Runx2					1482:1486	Runx2	1482:1486	Runx2	1482:1486	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	6	30	theme	marker	1042:1047	arg1	mRNAs					1054:1058	osteogenic marker gene mRNAs	1031:1058	osteogenic marker gene mRNAs	1031:1058	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	31	theme	transcriptional	1099:1113	arg1	activity					1115:1122	transcriptional activity	1099:1122	transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation	1099:1214	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	9	32	theme	excessive	1773:1781	arg1	O-GlcNAcylation					1791:1805	excessive protein O-GlcNAcylation	1773:1805	excessive protein O-GlcNAcylation	1773:1805	Our findings suggest that excessive protein O-GlcNAcylation contributes to high glucose-suppressed osteogenic differentiation.
29315243	7	33	dep	increased	1286:1294	arg1	led					1376:1378	led	1376:1378	led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase	1376:1577	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	34	theme	expression	1436:1445	arg1	levels					1447:1452	expression levels	1436:1452	expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1436:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	1	35	theme	osteogenic	223:232	arg1	differentiation					234:248	osteogenic differentiation	223:248	osteogenic differentiation	223:248	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	5	36	theme	glucose	805:811	arg1	concentrations					850:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	7	37	from	decrease	1385:1392	arg1	activity					1546:1553	activity	1546:1553	activity of alkaline phosphatase	1546:1577	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	37	from	decrease	1385:1392	arg1	levels					1447:1452	expression levels	1436:1452	expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1436:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	37	from	decrease	1385:1392	arg1	activity					1417:1424	the transcriptional activity	1397:1424	the transcriptional activity of Runx2	1397:1433	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	1	38	theme	differentiation	234:248	arg1	modulation					209:218	the modulation	205:218	the modulation of osteogenic differentiation	205:248	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	3	39	theme	protein	433:439	arg1	O-GlcNAcylation					487:501	O-GlcNAcylation	487:501	O-GlcNAcylation	487:501	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	3	39	theme	protein	433:439	arg1	glycosylation					472:484	protein O-linked-β-N-acetylglucosamine glycosylation	433:484	protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	433:502	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	4	40	theme	recombinant	670:680	arg1	protein					707:713	recombinant human bone morphogenetic protein 2	670:715	recombinant human bone morphogenetic protein 2 (BMP2)	670:722	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	4	40	theme	recombinant	670:680	arg1	BMP2					718:721	BMP2	718:721	BMP2	718:721	To induce osteogenic differentiation, C2C12 cells were cultured in the presence of recombinant human bone morphogenetic protein 2 (BMP2).
29315243	7	41	theme	Cell	1217:1220	arg1	treatment					1222:1230	Cell treatment	1217:1230	Cell treatment with high glucose, glucosamine or N-acetylglucosamine	1217:1284	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	1	42	theme	diabetic	138:145	arg1	patients					147:154	diabetic patients	138:154	diabetic patients	138:154	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	6	43	theme	gene	1049:1052	arg1	mRNAs					1054:1058	osteogenic marker gene mRNAs	1031:1058	osteogenic marker gene mRNAs	1031:1058	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	7	44	theme	osteogenic	1457:1466	arg1	genes					1475:1479	osteogenic marker genes	1457:1479	osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1457:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	44	theme	osteogenic	1457:1466	arg1	osterix					1489:1495	osterix	1489:1495	osterix	1489:1495	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	44	theme	osteogenic	1457:1466	arg1	collagen					1531:1538	type I collagen	1524:1538	type I collagen	1524:1538	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	44	theme	osteogenic	1457:1466	arg1	phosphatase					1507:1517	alkaline phosphatase	1498:1517	alkaline phosphatase	1498:1517	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	44	theme	osteogenic	1457:1466	arg1	Runx2					1482:1486	Runx2	1482:1486	Runx2	1482:1486	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	0	45	theme	BMP2-Induced	54:65	arg1	Differentiation					78:92	BMP2-Induced Osteogenic Differentiation	54:92	BMP2-Induced Osteogenic Differentiation of C2C12 Cells	54:107	Conditions Inducing Excessive O-GlcNAcylation Inhibit BMP2-Induced Osteogenic Differentiation of C2C12 Cells.
29315243	6	46	theme	phosphatase	1082:1092	arg1	levels					1021:1026	the expression levels	1006:1026	the expression levels of osteogenic marker gene mRNAs	1006:1058	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	46	theme	phosphatase	1082:1092	arg1	activity					1115:1122	transcriptional activity	1099:1122	transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation	1099:1214	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	46	theme	phosphatase	1082:1092	arg1	activity					1061:1068	activity	1061:1068	activity of alkaline phosphatase	1061:1092	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	5	47	theme	glucosamine	814:824	arg1	concentrations					850:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	6	48	theme	osteoblast	1170:1179	arg1	differentiation					1181:1195	osteoblast differentiation	1170:1195	osteoblast differentiation	1170:1195	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	49	theme	bone	1201:1204	arg1	formation					1206:1214	bone formation	1201:1214	bone formation	1201:1214	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	3	50	theme	osteogenic	538:547	arg1	differentiation					549:563	osteogenic differentiation	538:563	osteogenic differentiation	538:563	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	7	51	theme	Runx2	1315:1319	arg1	O-GlcNAcylation					1296:1310	O-GlcNAcylation	1296:1310	O-GlcNAcylation of Runx2	1296:1319	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	51	theme	Runx2	1315:1319	arg1	levels					1335:1340	the total levels	1325:1340	the total levels of O-GlcNAcylated proteins	1325:1367	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	6	52	theme	alkaline	1073:1080	arg1	phosphatase					1082:1092	alkaline phosphatase	1073:1092	alkaline phosphatase	1073:1092	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	53	theme	Runx2	1127:1131	arg1	levels					1021:1026	the expression levels	1006:1026	the expression levels of osteogenic marker gene mRNAs	1006:1058	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	53	theme	Runx2	1127:1131	arg1	activity					1115:1122	transcriptional activity	1099:1122	transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation	1099:1214	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	53	theme	Runx2	1127:1131	arg1	activity					1061:1068	activity	1061:1068	activity of alkaline phosphatase	1061:1092	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	8	54	theme	inhibitory	1586:1595	arg1	effects					1597:1603	These inhibitory effects	1580:1603	These inhibitory effects	1580:1603	These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β-N-acetylglucosaminidase.
29315243	7	55	theme	type	1524:1527	arg1	genes					1475:1479	osteogenic marker genes	1457:1479	osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1457:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	55	theme	type	1524:1527	arg1	collagen					1531:1538	type I collagen	1524:1538	type I collagen	1524:1538	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	3	56	theme	differentiation	549:563	arg1	suppression					523:533	the suppression	519:533	the suppression of osteogenic differentiation due to hyperglycemia	519:584	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	7	57	theme	proteins	1360:1367	arg1	O-GlcNAcylation					1296:1310	O-GlcNAcylation	1296:1310	O-GlcNAcylation of Runx2	1296:1319	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	57	theme	proteins	1360:1367	arg1	levels					1335:1340	the total levels	1325:1340	the total levels of O-GlcNAcylated proteins	1325:1367	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	5	58	theme	C2C12	783:787	arg1	cells					789:793	C2C12 cells	783:793	C2C12 cells	783:793	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	3	59	from	increase	421:428	arg1	O-GlcNAcylation					487:501	O-GlcNAcylation	487:501	O-GlcNAcylation	487:501	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	3	59	from	increase	421:428	arg1	glycosylation					472:484	protein O-linked-β-N-acetylglucosamine glycosylation	433:484	protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation)	433:502	This study aimed to investigate whether the aberrant increase in protein O-linked-β-N-acetylglucosamine glycosylation (O-GlcNAcylation) contributes to the suppression of osteogenic differentiation due to hyperglycemia.
29315243	2	60	theme	molecular	264:272	arg1	mechanisms					274:283	the molecular mechanisms	260:283	the molecular mechanisms by which hyperglycemia affects osteogenic differentiation	260:341	However, the molecular mechanisms by which hyperglycemia affects osteogenic differentiation are yet to be clarified.
29315243	7	61	theme	phosphatase	1567:1577	arg1	activity					1546:1553	activity	1546:1553	activity of alkaline phosphatase	1546:1577	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	61	theme	phosphatase	1567:1577	arg1	levels					1447:1452	expression levels	1436:1452	expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1436:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	61	theme	phosphatase	1567:1577	arg1	activity					1417:1424	the transcriptional activity	1397:1424	the transcriptional activity of Runx2	1397:1433	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	62	theme	Runx2	1429:1433	arg1	activity					1546:1553	activity	1546:1553	activity of alkaline phosphatase	1546:1577	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	62	theme	Runx2	1429:1433	arg1	levels					1447:1452	expression levels	1436:1452	expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1436:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	62	theme	Runx2	1429:1433	arg1	activity					1417:1424	the transcriptional activity	1397:1424	the transcriptional activity of Runx2	1397:1433	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	0	63	theme	Osteogenic	67:76	arg1	Differentiation					78:92	BMP2-Induced Osteogenic Differentiation	54:92	BMP2-Induced Osteogenic Differentiation of C2C12 Cells	54:107	Conditions Inducing Excessive O-GlcNAcylation Inhibit BMP2-Induced Osteogenic Differentiation of C2C12 Cells.
29315243	7	64	theme	genes	1475:1479	arg1	activity					1546:1553	activity	1546:1553	activity of alkaline phosphatase	1546:1577	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	64	theme	genes	1475:1479	arg1	levels					1447:1452	expression levels	1436:1452	expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1436:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	64	theme	genes	1475:1479	arg1	activity					1417:1424	the transcriptional activity	1397:1424	the transcriptional activity of Runx2	1397:1433	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	8	65	dep	lowering	1621:1628	arg1	adding					1664:1669	adding	1664:1669	adding STO45849, an OGT inhibitor	1664:1696	These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β-N-acetylglucosaminidase.
29315243	8	65	dep	lowering	1621:1628	arg1	overexpressing					1705:1718	overexpressing	1705:1718	overexpressing β-N-acetylglucosaminidase	1705:1744	These inhibitory effects were rescued by lowering protein O-GlcNAcylation levels by adding STO45849, an OGT inhibitor, or by overexpressing β-N-acetylglucosaminidase.
29315243	2	66	theme	osteogenic	316:325	arg1	differentiation					327:341	osteogenic differentiation	316:341	osteogenic differentiation	316:341	However, the molecular mechanisms by which hyperglycemia affects osteogenic differentiation are yet to be clarified.
29315243	7	67	dep	genes	1475:1479	arg1	genes					1475:1479	osteogenic marker genes	1457:1479	osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1457:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	67	dep	genes	1475:1479	arg1	osterix					1489:1495	osterix	1489:1495	osterix	1489:1495	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	67	dep	genes	1475:1479	arg1	collagen					1531:1538	type I collagen	1524:1538	type I collagen	1524:1538	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	67	dep	genes	1475:1479	arg1	phosphatase					1507:1517	alkaline phosphatase	1498:1517	alkaline phosphatase	1498:1517	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	67	dep	genes	1475:1479	arg1	Runx2					1482:1486	Runx2	1482:1486	Runx2	1482:1486	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	5	68	theme	high	800:803	arg1	concentrations					850:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	high glucose, glucosamine, or N-acetylglucosamine concentrations	800:863	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	6	69	theme	osteoblast	947:956	arg1	differentiation					958:972	osteoblast differentiation	947:972	osteoblast differentiation	947:972	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	7	70	theme	alkaline	1498:1505	arg1	genes					1475:1479	osteogenic marker genes	1457:1479	osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen)	1457:1539	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	7	70	theme	alkaline	1498:1505	arg1	phosphatase					1507:1517	alkaline phosphatase	1498:1517	alkaline phosphatase	1498:1517	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29315243	1	71	theme	various	167:173	arg1	functions					184:192	various cellular functions	167:192	various cellular functions	167:192	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	1	71	theme	various	167:173	arg1	modulation					209:218	the modulation	205:218	the modulation of osteogenic differentiation	205:248	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	6	72	theme	transcription	1145:1157	arg1	Runx2					1127:1131	Runx2	1127:1131	Runx2	1127:1131	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	72	theme	transcription	1145:1157	arg1	factor					1159:1164	a critical transcription factor	1134:1164	a critical transcription factor for osteoblast differentiation and bone formation	1134:1214	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	0	73	theme	C2C12	97:101	arg1	Cells					103:107	C2C12 Cells	97:107	C2C12 Cells	97:107	Conditions Inducing Excessive O-GlcNAcylation Inhibit BMP2-Induced Osteogenic Differentiation of C2C12 Cells.
29315243	9	74	theme	protein	1783:1789	arg1	O-GlcNAcylation					1791:1805	excessive protein O-GlcNAcylation	1773:1805	excessive protein O-GlcNAcylation	1773:1805	Our findings suggest that excessive protein O-GlcNAcylation contributes to high glucose-suppressed osteogenic differentiation.
29315243	1	75	theme	cellular	175:182	arg1	functions					184:192	various cellular functions	167:192	various cellular functions	167:192	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	1	75	theme	cellular	175:182	arg1	modulation					209:218	the modulation	205:218	the modulation of osteogenic differentiation	205:248	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	1	76	from	conditions	124:133	arg1	patients					147:154	diabetic patients	138:154	diabetic patients	138:154	Hyperglycemic conditions in diabetic patients can affect various cellular functions, including the modulation of osteogenic differentiation.
29315243	6	77	theme	critical	1136:1143	arg1	Runx2					1127:1131	Runx2	1127:1131	Runx2	1127:1131	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	77	theme	critical	1136:1143	arg1	factor					1159:1164	a critical transcription factor	1134:1164	a critical transcription factor for osteoblast differentiation and bone formation	1134:1214	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	5	78	theme	O-GlcNAc	871:878	arg1	OGT					893:895	OGT	893:895	OGT	893:895	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	5	78	theme	O-GlcNAc	871:878	arg1	transferase					880:890	O-GlcNAc transferase	871:890	O-GlcNAc transferase (OGT) overexpression	871:911	Excessive protein O-GlcNAcylation was induced by treating C2C12 cells with high glucose, glucosamine, or N-acetylglucosamine concentrations or by O-GlcNAc transferase (OGT) overexpression.
29315243	6	79	theme	mRNAs	1054:1058	arg1	levels					1021:1026	the expression levels	1006:1026	the expression levels of osteogenic marker gene mRNAs	1006:1058	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	79	theme	mRNAs	1054:1058	arg1	activity					1115:1122	transcriptional activity	1099:1122	transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation	1099:1214	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	6	79	theme	mRNAs	1054:1058	arg1	activity					1061:1068	activity	1061:1068	activity of alkaline phosphatase	1061:1092	The effect of O-GlcNAcylation on osteoblast differentiation was then confirmed by examining the expression levels of osteogenic marker gene mRNAs, activity of alkaline phosphatase, and transcriptional activity of Runx2, a critical transcription factor for osteoblast differentiation and bone formation.
29315243	0	80	theme	Excessive	20:28	arg1	O-GlcNAcylation					30:44	Excessive O-GlcNAcylation	20:44	Excessive O-GlcNAcylation	20:44	Conditions Inducing Excessive O-GlcNAcylation Inhibit BMP2-Induced Osteogenic Differentiation of C2C12 Cells.
29315243	7	81	theme	transcriptional	1401:1415	arg1	activity					1417:1424	the transcriptional activity	1397:1424	the transcriptional activity of Runx2	1397:1433	Cell treatment with high glucose, glucosamine or N-acetylglucosamine increased O-GlcNAcylation of Runx2 and the total levels of O-GlcNAcylated proteins, which led to a decrease in the transcriptional activity of Runx2, expression levels of osteogenic marker genes (Runx2, osterix, alkaline phosphatase, and type I collagen), and activity of alkaline phosphatase.
29263294	5	0	link	O-linked	895:902	arg1	O-GlcNAcylation					925:939	O-GlcNAcylation	925:939	O-GlcNAcylation	925:939	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	0	link	O-linked	895:902	arg1	N-acetylglucosamine					904:922	O-linked N-acetylglucosamine	895:922	O-linked N-acetylglucosamine (O-GlcNAcylation)	895:940	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	1	attach	interlinked	775:785	arg3	increase					813:820	a Nox4-ATF4-dependent increase	791:820	a Nox4-ATF4-dependent increase	791:820	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	2	theme	acid	955:958	arg1	CD36					972:975	the fatty acid transporter CD36	945:975	the fatty acid transporter CD36	945:975	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	0	3	theme	stress	84:89	arg1	adaptation					91:100	stress adaptation	84:100	stress adaptation	84:100	Nox4 reprograms cardiac substrate metabolism via protein O-GlcNAcylation to enhance stress adaptation.
29263294	5	4	theme	transporter	960:970	arg1	CD36					972:975	the fatty acid transporter CD36	945:975	the fatty acid transporter CD36	945:975	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	2	5	theme	mechanistic	310:320	arg1	interrelationship					322:338	The mechanistic interrelationship	306:338	The mechanistic interrelationship between altered energy metabolism, remodeling, and function	306:398	The mechanistic interrelationship between altered energy metabolism, remodeling, and function remains unclear.
29263294	6	6	theme	cardiac	1121:1127	arg1	metabolism					1139:1148	cardiac substrate metabolism	1121:1148	cardiac substrate metabolism	1121:1148	These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress.
29263294	4	7	theme	fatty	627:631	arg1	oxidation					638:646	fatty acid oxidation	627:646	fatty acid oxidation	627:646	Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses.
29263294	5	8	theme	acid	996:999	arg1	utilization					1001:1011	fatty acid utilization	990:1011	fatty acid utilization	990:1011	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	7	9	from	oxidation	1251:1259	arg1	heart					1289:1293	the chronically stressed heart	1264:1293	the chronically stressed heart	1264:1293	Our results also suggest that increased fatty acid oxidation in the chronically stressed heart may be beneficial.
29263294	6	10	theme	novel	1047:1051	arg1	pathway					1059:1065	a potentially novel redox pathway	1033:1065	a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress	1033:1197	These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress.
29263294	6	11	theme	chronic	1184:1190	arg1	stress					1192:1197	chronic stress	1184:1197	chronic stress	1184:1197	These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress.
29263294	5	12	theme	O-linked	895:902	arg1	O-GlcNAcylation					925:939	O-GlcNAcylation	925:939	O-GlcNAcylation	925:939	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	12	theme	O-linked	895:902	arg1	N-acetylglucosamine					904:922	O-linked N-acetylglucosamine	895:922	O-linked N-acetylglucosamine (O-GlcNAcylation)	895:940	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	7	13	theme	stressed	1280:1287	arg1	heart					1289:1293	the chronically stressed heart	1264:1293	the chronically stressed heart	1264:1293	Our results also suggest that increased fatty acid oxidation in the chronically stressed heart may be beneficial.
29263294	4	14	from	oxidation	603:611	arg1	metabolism					582:591	glucose metabolism	574:591	glucose metabolism away from oxidation	574:611	Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses.
29263294	4	15	theme	acute	695:699	arg1	stresses					712:719	acute or chronic stresses	695:719	acute or chronic stresses	695:719	Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses.
29263294	3	16	theme	ROS-generating	421:434	arg1	Nox4					453:456	Nox4	453:456	Nox4	453:456	The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling.
29263294	3	16	theme	ROS-generating	421:434	arg1	oxidase-4					442:450	The ROS-generating NADPH oxidase-4	417:450	The ROS-generating NADPH oxidase-4 (Nox4)	417:457	The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling.
29263294	2	17	theme	energy	356:361	arg1	metabolism					363:372	altered energy metabolism	348:372	altered energy metabolism	348:372	The mechanistic interrelationship between altered energy metabolism, remodeling, and function remains unclear.
29263294	1	18	theme	preferred	200:208	arg1	substrate					217:225	preferred energy substrate	200:225	preferred energy substrate	200:225	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	3	19	theme	NADPH	436:440	arg1	Nox4					453:456	Nox4	453:456	Nox4	453:456	The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling.
29263294	3	19	theme	NADPH	436:440	arg1	oxidase-4					442:450	The ROS-generating NADPH oxidase-4	417:450	The ROS-generating NADPH oxidase-4 (Nox4)	417:457	The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling.
29263294	7	20	theme	acid	1246:1249	arg1	oxidation					1251:1259	increased fatty acid oxidation	1230:1259	increased fatty acid oxidation in the chronically stressed heart	1230:1293	Our results also suggest that increased fatty acid oxidation in the chronically stressed heart may be beneficial.
29263294	2	21	theme	altered	348:354	arg1	metabolism					363:372	altered energy metabolism	348:372	altered energy metabolism	348:372	The mechanistic interrelationship between altered energy metabolism, remodeling, and function remains unclear.
29263294	1	22	theme	energy	210:215	arg1	substrate					217:225	preferred energy substrate	200:225	preferred energy substrate	200:225	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	0	23	theme	substrate	24:32	arg1	metabolism					34:43	cardiac substrate metabolism	16:43	cardiac substrate metabolism	16:43	Nox4 reprograms cardiac substrate metabolism via protein O-GlcNAcylation to enhance stress adaptation.
29263294	4	24	theme	glucose	574:580	arg1	metabolism					582:591	glucose metabolism	574:591	glucose metabolism away from oxidation	574:611	Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses.
29263294	1	25	theme	hypertrophic	111:122	arg1	remodeling					124:133	Cardiac hypertrophic remodeling	103:133	Cardiac hypertrophic remodeling during chronic hemodynamic stress	103:167	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	4	26	theme	cardiac	669:675	arg1	energetics					677:686	cardiac energetics	669:686	cardiac energetics	669:686	Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses.
29263294	1	27	theme	Cardiac	103:109	arg1	remodeling					124:133	Cardiac hypertrophic remodeling	103:133	Cardiac hypertrophic remodeling during chronic hemodynamic stress	103:167	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	6	28	theme	substrate	1129:1137	arg1	metabolism					1139:1148	cardiac substrate metabolism	1121:1148	cardiac substrate metabolism	1121:1148	These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress.
29263294	7	29	theme	fatty	1240:1244	arg1	oxidation					1251:1259	increased fatty acid oxidation	1230:1259	increased fatty acid oxidation in the chronically stressed heart	1230:1293	Our results also suggest that increased fatty acid oxidation in the chronically stressed heart may be beneficial.
29263294	5	30	theme	fatty	749:753	arg1	metabolism					760:769	fatty acid metabolism	749:769	fatty acid metabolism	749:769	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	3	31	theme	overloaded	481:490	arg1	heart					492:496	the overloaded heart	477:496	the overloaded heart	477:496	The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling.
29263294	4	32	theme	chronic	704:710	arg1	stresses					712:719	acute or chronic stresses	695:719	acute or chronic stresses	695:719	Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses.
29263294	1	33	theme	fatty	232:236	arg1	acids					238:242	fatty acids	232:242	fatty acids	232:242	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	5	34	theme	hexosamine	829:838	arg1	pathway					853:859	the hexosamine biosynthetic pathway	825:859	the hexosamine biosynthetic pathway	825:859	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	35	theme	acid	755:758	arg1	metabolism					760:769	fatty acid metabolism	749:769	fatty acid metabolism	749:769	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	36	theme	N-acetylglucosamine	904:922	arg1	attachment					881:890	the attachment	877:890	the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36	877:975	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	37	theme	biosynthetic	840:851	arg1	pathway					853:859	the hexosamine biosynthetic pathway	825:859	the hexosamine biosynthetic pathway	825:859	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	1	38	from	acids	238:242	arg1	switch					190:195	a switch	188:195	a switch	188:195	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	3	39	theme	adverse	520:526	arg1	remodeling					528:537	adverse remodeling	520:537	adverse remodeling	520:537	The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling.
29263294	0	40	theme	protein	49:55	arg1	O-GlcNAcylation					57:71	protein O-GlcNAcylation	49:71	protein O-GlcNAcylation	49:71	Nox4 reprograms cardiac substrate metabolism via protein O-GlcNAcylation to enhance stress adaptation.
29263294	5	41	from	increase	813:820	arg1	pathway					853:859	the hexosamine biosynthetic pathway	825:859	the hexosamine biosynthetic pathway	825:859	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	6	42	theme	redox	1053:1057	arg1	pathway					1059:1065	a potentially novel redox pathway	1033:1065	a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress	1033:1197	These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress.
29263294	1	43	theme	chronic	142:148	arg1	stress					162:167	chronic hemodynamic stress	142:167	chronic hemodynamic stress	142:167	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	5	44	attach	attachment	881:890	arg2	O-GlcNAcylation					925:939	O-GlcNAcylation	925:939	O-GlcNAcylation	925:939	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	44	attach	attachment	881:890	arg2	N-acetylglucosamine					904:922	O-linked N-acetylglucosamine	895:922	O-linked N-acetylglucosamine (O-GlcNAcylation)	895:940	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	44	attach	attachment	881:890	arg1	CD36					972:975	the fatty acid transporter CD36	945:975	the fatty acid transporter CD36	945:975	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	7	45	theme	increased	1230:1238	arg1	oxidation					1251:1259	increased fatty acid oxidation	1230:1259	increased fatty acid oxidation in the chronically stressed heart	1230:1293	Our results also suggest that increased fatty acid oxidation in the chronically stressed heart may be beneficial.
29263294	1	46	theme	hemodynamic	150:160	arg1	stress					162:167	chronic hemodynamic stress	142:167	chronic hemodynamic stress	142:167	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	5	47	from	changes	726:732	arg1	metabolism					760:769	fatty acid metabolism	749:769	fatty acid metabolism	749:769	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	47	from	changes	726:732	arg1	glucose					737:743	glucose	737:743	glucose	737:743	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	5	48	theme	fatty	990:994	arg1	acid					996:999	fatty acid	990:999	fatty acid utilization	990:1011	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	4	49	theme	acid	633:636	arg1	oxidation					638:646	fatty acid oxidation	627:646	fatty acid oxidation	627:646	Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses.
29263294	6	50	theme	protein	1082:1088	arg1	O-GlcNAcylation					1090:1104	protein O-GlcNAcylation	1082:1104	protein O-GlcNAcylation	1082:1104	These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress.
29263294	5	51	theme	Nox4-ATF4-dependent	793:811	arg1	increase					813:820	a Nox4-ATF4-dependent increase	791:820	a Nox4-ATF4-dependent increase	791:820	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
29263294	0	52	theme	cardiac	16:22	arg1	metabolism					34:43	cardiac substrate metabolism	16:43	cardiac substrate metabolism	16:43	Nox4 reprograms cardiac substrate metabolism via protein O-GlcNAcylation to enhance stress adaptation.
29263294	1	53	from	switch	190:195	arg1	substrate					217:225	preferred energy substrate	200:225	preferred energy substrate	200:225	Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable.
29263294	5	54	theme	fatty	949:953	arg1	CD36					972:975	the fatty acid transporter CD36	945:975	the fatty acid transporter CD36	945:975	The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization.
28487326	6	0	theme	METHODS	951:957	arg1	Mice					959:962	METHODS Mice	951:962	METHODS Mice with Xbp1 loss and gain of function in neurons	951:1009	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	3	1	link	O-linked	644:651	arg1	O-GlcNAcylation					702:716	O-GlcNAcylation	702:716	O-GlcNAcylation	702:716	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	1	link	O-linked	644:651	arg1	modification					676:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification	634:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)	634:717	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	14	2	theme	stroke	1776:1781	arg1	penumbra					1783:1790	the stroke penumbra	1772:1790	the stroke penumbra in young mice	1772:1804	O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice.
28487326	15	3	theme	age-related	1885:1895	arg1	decline					1897:1903	the age-related decline	1881:1903	the age-related decline in the brain's self-healing capacity	1881:1940	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	3	4	theme	inositol-requiring	557:574	arg1	sensor					549:554	the endoplasmic reticulum stress sensor	516:554	the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1)	516:584	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	4	theme	inositol-requiring	557:574	arg1	enzyme-1					576:583	inositol-requiring enzyme-1	557:583	inositol-requiring enzyme-1	557:583	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	1	5	theme	key	268:270	arg1	BACKGROUND					166:175	BACKGROUND	166:175	BACKGROUND	166:175	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	5	theme	key	268:270	arg1	feature					272:278	a key feature	266:278	a key feature of a variety of age-related brain diseases including stroke	266:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	5	theme	key	268:270	arg1	homeostasis					206:216	PURPOSE Impaired protein homeostasis	181:216	PURPOSE Impaired protein homeostasis	181:216	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	13	6	theme	IRE1/XBP1	1648:1656	arg1	branch					1684:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	6	7	theme	function	991:998	arg1	loss					974:977	Xbp1 loss	969:977	Xbp1 loss	969:977	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	6	7	theme	function	991:998	arg1	gain					983:986	gain	983:986	gain of function in neurons	983:1009	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	7	8	theme	cerebral	1096:1103	arg1	artery					1105:1110	the middle cerebral artery	1085:1110	the middle cerebral artery	1085:1110	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	9	9	theme	middle	1256:1261	arg1	occlusion					1279:1287	permanent middle cerebral artery occlusion	1246:1287	permanent middle cerebral artery occlusion	1246:1287	RESULTS Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion.
28487326	13	10	theme	critical	1626:1633	arg1	role					1635:1638	a critical role	1624:1638	a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome	1624:1707	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	1	11	theme	Impaired	189:196	arg1	BACKGROUND					166:175	BACKGROUND	166:175	BACKGROUND	166:175	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	11	theme	Impaired	189:196	arg1	feature					272:278	a key feature	266:278	a key feature of a variety of age-related brain diseases including stroke	266:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	11	theme	Impaired	189:196	arg1	homeostasis					206:216	PURPOSE Impaired protein homeostasis	181:216	PURPOSE Impaired protein homeostasis	181:216	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	15	12	from	outcome	1999:2005	arg1	brains					2015:2020	aged brains	2010:2020	aged brains	2010:2020	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	9	13	theme	artery	1272:1277	arg1	occlusion					1279:1287	permanent middle cerebral artery occlusion	1246:1287	permanent middle cerebral artery occlusion	1246:1287	RESULTS Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion.
28487326	5	14	theme	IRE1/XBP1/O-GlcNAc	875:892	arg1	axis					894:897	the IRE1/XBP1/O-GlcNAc axis	871:897	the IRE1/XBP1/O-GlcNAc axis	871:897	The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke.
28487326	0	15	from	Neuroprotective	60:74	arg1	Stroke					88:93	Ischemic Stroke	79:93	Ischemic Stroke in Young Mice	79:107	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	4	16	theme	endoplasmic	735:745	arg1	function					757:764	endoplasmic reticulum function	735:764	endoplasmic reticulum function	735:764	Stroke impairs endoplasmic reticulum function, which activates unfolded protein response.
28487326	15	17	theme	self-healing	1920:1931	arg1	capacity					1933:1940	the brain's self-healing capacity	1908:1940	the brain's self-healing capacity	1908:1940	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	14	18	theme	prosurvival	1731:1741	arg1	O-GlcNAcylation					1710:1724	O-GlcNAcylation	1710:1724	O-GlcNAcylation	1710:1724	O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice.
28487326	14	18	theme	prosurvival	1731:1741	arg1	pathway					1743:1749	a prosurvival pathway	1729:1749	a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice	1729:1830	O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice.
28487326	3	19	theme	downstream	593:602	arg1	protein-1					618:626	downstream X-box-binding protein-1	593:626	downstream X-box-binding protein-1	593:626	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	19	theme	downstream	593:602	arg1	XBP1					587:590	XBP1	587:590	XBP1 (downstream X-box-binding protein-1)	587:627	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	10	20	gly	O-GlcNAcylation	1304:1318	arg1	neurons					1337:1343	neurons	1337:1343	neurons	1337:1343	After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.
28487326	3	21	theme	O-GlcNAc	634:641	arg1	O-GlcNAcylation					702:716	O-GlcNAcylation	702:716	O-GlcNAcylation	702:716	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	21	theme	O-GlcNAc	634:641	arg1	modification					676:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification	634:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)	634:717	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	15	22	theme	aged	2010:2013	arg1	brains					2015:2020	aged brains	2010:2020	aged brains	2010:2020	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	0	23	theme	Ischemic	79:86	arg1	Stroke					88:93	Ischemic Stroke	79:93	Ischemic Stroke in Young Mice	79:107	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	5	24	theme	ischemic	934:941	arg1	stroke					943:948	ischemic stroke	934:948	ischemic stroke	934:948	The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke.
28487326	15	25	theme	ischemic	1983:1990	arg1	outcome					1999:2005	ischemic stroke outcome	1983:2005	ischemic stroke outcome in aged brains	1983:2020	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	3	26	theme	response	470:477	arg1	pathway					491:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	10	27	from	penumbra	1359:1366	arg1	mice					1377:1380	young mice	1371:1380	young mice	1371:1380	After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.
28487326	15	28	theme	Boosting	1833:1840	arg1	strategy					1963:1970	a promising strategy	1951:1970	a promising strategy to improve ischemic stroke outcome in aged brains	1951:2020	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	15	28	theme	Boosting	1833:1840	arg1	pathways					1854:1861	Boosting prosurvival pathways	1833:1861	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity	1833:1940	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	9	29	dep	RESULTS	1184:1190	arg1	worsened					1209:1216	worsened	1209:1216	worsened outcome after transient and permanent middle cerebral artery occlusion	1209:1287	RESULTS Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion.
28487326	4	30	theme	unfolded	783:790	arg1	response					800:807	unfolded protein response	783:807	unfolded protein response	783:807	Stroke impairs endoplasmic reticulum function, which activates unfolded protein response.
28487326	3	31	theme	protein	462:468	arg1	pathway					491:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	0	32	theme	X-Box-Binding	6:18	arg1	Protein-1					20:28	X-Box-Binding Protein-1	6:28	X-Box-Binding Protein-1	6:28	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	13	33	theme	stroke	1694:1699	arg1	outcome					1701:1707	stroke outcome	1694:1707	stroke outcome	1694:1707	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	3	34	theme	key	449:451	arg1	pathway					491:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	2	35	theme	unfolded	407:414	arg1	response					424:431	the unfolded protein response	403:431	the unfolded protein response	403:431	To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated.
28487326	13	36	theme	unfolded	1658:1665	arg1	branch					1684:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	3	37	theme	O-linked	644:651	arg1	O-GlcNAcylation					702:716	O-GlcNAcylation	702:716	O-GlcNAcylation	702:716	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	37	theme	O-linked	644:651	arg1	modification					676:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification	634:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)	634:717	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	10	38	theme	young	1371:1375	arg1	mice					1377:1380	young mice	1371:1380	young mice	1371:1380	After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.
28487326	5	39	theme	study	832:836	arg1	rationale					814:822	The rationale	810:822	The rationale of this study	810:836	The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke.
28487326	1	40	theme	brain	308:312	arg1	stroke					333:338	stroke	333:338	stroke	333:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	40	theme	brain	308:312	arg1	diseases					314:321	age-related brain diseases	296:321	age-related brain diseases including stroke	296:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	13	41	theme	response	1675:1682	arg1	branch					1684:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	10	42	theme	penumbra	1359:1366	arg1	neurons					1337:1343	neurons	1337:1343	neurons	1337:1343	After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.
28487326	3	43	theme	prosurvival	479:489	arg1	pathway					491:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	44	theme	endoplasmic	520:530	arg1	reticulum					532:540	the endoplasmic reticulum	516:540	the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1)	516:584	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	1	45	theme	endoplasmic	229:239	arg1	reticulum					241:249	endoplasmic reticulum	229:249	endoplasmic reticulum dysfunction	229:261	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	12	46	theme	Pharmacological	1479:1493	arg1	increase					1495:1502	Pharmacological increase	1479:1502	Pharmacological increase of O-GlcNAcylation before or after stroke	1479:1544	Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice.
28487326	7	47	from	occlusion	1072:1080	arg1	mice					1130:1133	young and aged mice	1115:1133	young and aged mice	1115:1133	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	2	48	theme	endoplasmic	352:362	arg1	reticulum					364:372	endoplasmic reticulum	352:372	endoplasmic reticulum function	352:381	To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated.
28487326	13	49	from	role	1635:1638	arg1	outcome					1701:1707	stroke outcome	1694:1707	stroke outcome	1694:1707	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	11	50	theme	O-GlcNAcylation	1436:1450	arg1	activation					1422:1431	This activation	1417:1431	This activation of O-GlcNAcylation	1417:1450	This activation of O-GlcNAcylation was impaired in aged mice.
28487326	7	51	theme	aged	1125:1128	arg1	mice					1130:1133	young and aged mice	1115:1133	young and aged mice	1115:1133	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	9	52	theme	Xbp1	1204:1207	arg1	Deletion					1192:1199	Deletion	1192:1199	Deletion of Xbp1	1192:1207	RESULTS Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion.
28487326	8	53	used	used	1150:1153	arg2	Thiamet-G					1136:1144	Thiamet-G	1136:1144	Thiamet-G	1136:1144	Thiamet-G was used to increase O-GlcNAcylation.
28487326	7	54	theme	young	1115:1119	arg1	mice					1130:1133	young and aged mice	1115:1133	young and aged mice	1115:1133	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	3	55	theme	stress	542:547	arg1	sensor					549:554	the endoplasmic reticulum stress sensor	516:554	the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1)	516:584	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	55	theme	stress	542:547	arg1	enzyme-1					576:583	inositol-requiring enzyme-1	557:583	inositol-requiring enzyme-1	557:583	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	5	56	theme	axis	894:897	arg1	potentials					857:866	the potentials	853:866	the potentials of the IRE1/XBP1/O-GlcNAc axis	853:897	The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke.
28487326	5	56	theme	axis	894:897	arg1	target					904:909	a target	902:909	a target for neuroprotection in ischemic stroke	902:948	The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke.
28487326	15	57	theme	promising	1953:1961	arg1	pathways					1854:1861	Boosting prosurvival pathways	1833:1861	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity	1833:1940	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	15	57	theme	promising	1953:1961	arg1	strategy					1963:1970	a promising strategy	1951:1970	a promising strategy to improve ischemic stroke outcome in aged brains	1951:2020	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	7	58	theme	artery	1105:1110	arg1	occlusion					1072:1080	transient or permanent occlusion	1049:1080	transient or permanent occlusion of the middle cerebral artery in young and aged mice	1049:1133	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	15	59	from	decline	1897:1903	arg1	capacity					1933:1940	the brain's self-healing capacity	1908:1940	the brain's self-healing capacity	1908:1940	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	7	60	theme	middle	1089:1094	arg1	artery					1105:1110	the middle cerebral artery	1085:1110	the middle cerebral artery	1085:1110	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	9	61	theme	permanent	1246:1254	arg1	occlusion					1279:1287	permanent middle cerebral artery occlusion	1246:1287	permanent middle cerebral artery occlusion	1246:1287	RESULTS Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion.
28487326	1	62	theme	PURPOSE	181:187	arg1	BACKGROUND					166:175	BACKGROUND	166:175	BACKGROUND	166:175	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	62	theme	PURPOSE	181:187	arg1	feature					272:278	a key feature	266:278	a key feature of a variety of age-related brain diseases including stroke	266:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	62	theme	PURPOSE	181:187	arg1	homeostasis					206:216	PURPOSE Impaired protein homeostasis	181:216	PURPOSE Impaired protein homeostasis	181:216	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	0	63	from	Stroke	88:93	arg1	Neuroprotective					60:74	Neuroprotective	60:74	Neuroprotective	60:74	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	0	63	from	Stroke	88:93	arg1	Mice					104:107	Young Mice	98:107	Young Mice	98:107	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	0	64	theme	Aged	131:134	arg1	Mice					136:139	Aged Mice	131:139	Aged Mice	131:139	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	9	65	theme	cerebral	1263:1270	arg1	occlusion					1279:1287	permanent middle cerebral artery occlusion	1246:1287	permanent middle cerebral artery occlusion	1246:1287	RESULTS Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion.
28487326	3	66	theme	X-box-binding	604:616	arg1	protein-1					618:626	downstream X-box-binding protein-1	593:626	downstream X-box-binding protein-1	593:626	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	66	theme	X-box-binding	604:616	arg1	XBP1					587:590	XBP1	587:590	XBP1 (downstream X-box-binding protein-1)	587:627	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	1	67	theme	protein	198:204	arg1	BACKGROUND					166:175	BACKGROUND	166:175	BACKGROUND	166:175	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	67	theme	protein	198:204	arg1	feature					272:278	a key feature	266:278	a key feature of a variety of age-related brain diseases including stroke	266:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	67	theme	protein	198:204	arg1	homeostasis					206:216	PURPOSE Impaired protein homeostasis	181:216	PURPOSE Impaired protein homeostasis	181:216	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	7	68	theme	permanent	1062:1070	arg1	occlusion					1072:1080	transient or permanent occlusion	1049:1080	transient or permanent occlusion of the middle cerebral artery in young and aged mice	1049:1133	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	6	69	theme	Xbp1	969:972	arg1	loss					974:977	Xbp1 loss	969:977	Xbp1 loss	969:977	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	7	70	theme	transient	1049:1057	arg1	occlusion					1072:1080	transient or permanent occlusion	1049:1080	transient or permanent occlusion of the middle cerebral artery in young and aged mice	1049:1133	Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice.
28487326	15	71	dep	pathways	1854:1861	arg1	counterbalance					1866:1879	counterbalance	1866:1879	to counterbalance the age-related decline in the brain's self-healing capacity	1863:1940	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	10	72	from	neurons	1337:1343	arg1	mice					1377:1380	young mice	1371:1380	young mice	1371:1380	After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.
28487326	4	73	theme	reticulum	747:755	arg1	function					757:764	endoplasmic reticulum function	735:764	endoplasmic reticulum function	735:764	Stroke impairs endoplasmic reticulum function, which activates unfolded protein response.
28487326	3	74	mod	modification	676:687	arg3	O-GlcNAc					634:641	O-GlcNAc (O-linked β-N-acetylglucosamine) modification	634:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)	634:717	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	74	mod	modification	676:687	arg3	β-N-acetylglucosamine					653:673	O-GlcNAc (O-linked β-N-acetylglucosamine) modification	634:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)	634:717	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	74	mod	modification	676:687	arg1	proteins					692:699	proteins	692:699	proteins	692:699	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	12	75	theme	young	1571:1575	arg1	mice					1586:1589	both young and aged mice	1566:1589	both young and aged mice	1566:1589	Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice.
28487326	0	76	theme	Young	98:102	arg1	Mice					104:107	Young Mice	98:107	Young Mice	98:107	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	12	77	theme	aged	1581:1584	arg1	mice					1586:1589	both young and aged mice	1566:1589	both young and aged mice	1566:1589	Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice.
28487326	4	78	theme	protein	792:798	arg1	response					800:807	unfolded protein response	783:807	unfolded protein response	783:807	Stroke impairs endoplasmic reticulum function, which activates unfolded protein response.
28487326	11	79	theme	aged	1468:1471	arg1	mice					1473:1476	aged mice	1468:1476	aged mice	1468:1476	This activation of O-GlcNAcylation was impaired in aged mice.
28487326	14	80	from	penumbra	1783:1790	arg1	mice					1801:1804	young mice	1795:1804	young mice	1795:1804	O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice.
28487326	15	81	theme	prosurvival	1842:1852	arg1	strategy					1963:1970	a promising strategy	1951:1970	a promising strategy to improve ischemic stroke outcome in aged brains	1951:2020	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	15	81	theme	prosurvival	1842:1852	arg1	pathways					1854:1861	Boosting prosurvival pathways	1833:1861	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity	1833:1940	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	5	82	from	neuroprotection	915:929	arg1	stroke					943:948	ischemic stroke	934:948	ischemic stroke	934:948	The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke.
28487326	13	83	dep	CONCLUSIONS	1592:1602	arg1	indicates					1614:1622	indicates	1614:1622	indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome	1614:1707	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	15	84	theme	stroke	1992:1997	arg1	outcome					1999:2005	ischemic stroke outcome	1983:2005	ischemic stroke outcome in aged brains	1983:2020	Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.
28487326	10	85	from	mice	1377:1380	arg1	neurons					1337:1343	neurons	1337:1343	neurons	1337:1343	After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.
28487326	10	86	theme	stroke	1352:1357	arg1	penumbra					1359:1366	the stroke penumbra	1348:1366	the stroke penumbra in young mice	1348:1380	After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.
28487326	6	87	from	gain	983:986	arg1	neurons					1003:1009	neurons	1003:1009	neurons	1003:1009	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	3	88	theme	β-N-acetylglucosamine	653:673	arg1	O-GlcNAcylation					702:716	O-GlcNAcylation	702:716	O-GlcNAcylation	702:716	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	88	theme	β-N-acetylglucosamine	653:673	arg1	modification					676:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification	634:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)	634:717	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	2	89	theme	protein	416:422	arg1	response					424:431	the unfolded protein response	403:431	the unfolded protein response	403:431	To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated.
28487326	0	90	theme	-Dependent	30:39	arg1	O-GlcNAcylation					41:55	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation	0:55	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation	0:55	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	1	91	theme	variety	285:291	arg1	BACKGROUND					166:175	BACKGROUND	166:175	BACKGROUND	166:175	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	91	theme	variety	285:291	arg1	feature					272:278	a key feature	266:278	a key feature of a variety of age-related brain diseases including stroke	266:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	91	theme	variety	285:291	arg1	homeostasis					206:216	PURPOSE Impaired protein homeostasis	181:216	PURPOSE Impaired protein homeostasis	181:216	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	14	92	theme	aged	1822:1825	arg1	mice					1827:1830	aged mice	1822:1830	aged mice	1822:1830	O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice.
28487326	14	93	theme	young	1795:1799	arg1	mice					1801:1804	young mice	1795:1804	young mice	1795:1804	O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice.
28487326	3	94	theme	unfolded	453:460	arg1	pathway					491:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway	447:497	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	1	95	theme	age-related	296:306	arg1	stroke					333:338	stroke	333:338	stroke	333:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	95	theme	age-related	296:306	arg1	diseases					314:321	age-related brain diseases	296:321	age-related brain diseases including stroke	296:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	0	96	dep	-Dependent	30:39	arg1	Protein-1					20:28	X-Box-Binding Protein-1	6:28	X-Box-Binding Protein-1	6:28	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	13	97	theme	protein	1667:1673	arg1	branch					1684:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	the IRE1/XBP1 unfolded protein response branch	1644:1689	CONCLUSIONS Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome.
28487326	3	98	theme	proteins	692:699	arg1	protein-1					618:626	downstream X-box-binding protein-1	593:626	downstream X-box-binding protein-1	593:626	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	98	theme	proteins	692:699	arg1	enzyme-1					576:583	inositol-requiring enzyme-1	557:583	inositol-requiring enzyme-1	557:583	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	98	theme	proteins	692:699	arg1	O-GlcNAcylation					702:716	O-GlcNAcylation	702:716	O-GlcNAcylation	702:716	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	98	theme	proteins	692:699	arg1	XBP1					587:590	XBP1	587:590	XBP1 (downstream X-box-binding protein-1)	587:627	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	98	theme	proteins	692:699	arg1	sensor					549:554	the endoplasmic reticulum stress sensor	516:554	the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1)	516:584	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	98	theme	proteins	692:699	arg1	modification					676:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification	634:687	O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation)	634:717	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	1	99	theme	diseases	314:321	arg1	variety					285:291	a variety	283:291	a variety of age-related brain diseases including stroke	283:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	99	theme	diseases	314:321	arg1	stroke					333:338	stroke	333:338	stroke	333:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	1	99	theme	diseases	314:321	arg1	diseases					314:321	age-related brain diseases	296:321	age-related brain diseases including stroke	296:338	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
28487326	12	100	theme	O-GlcNAcylation	1507:1521	arg1	increase					1495:1502	Pharmacological increase	1479:1502	Pharmacological increase of O-GlcNAcylation before or after stroke	1479:1544	Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice.
28487326	6	101	with	Mice	959:962	arg1	loss					974:977	Xbp1 loss	969:977	Xbp1 loss	969:977	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	6	101	with	Mice	959:962	arg1	gain					983:986	gain	983:986	gain of function in neurons	983:1009	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	6	102	from	loss	974:977	arg1	neurons					1003:1009	neurons	1003:1009	neurons	1003:1009	METHODS Mice with Xbp1 loss and gain of function in neurons were generated.
28487326	2	103	theme	reticulum	364:372	arg1	function					374:381	endoplasmic reticulum function	352:381	endoplasmic reticulum function	352:381	To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated.
28487326	0	104	from	Impairment	117:126	arg1	Mice					136:139	Aged Mice	131:139	Aged Mice	131:139	XBP1 (X-Box-Binding Protein-1)-Dependent O-GlcNAcylation Is Neuroprotective in Ischemic Stroke in Young Mice and Its Impairment in Aged Mice Is Rescued by Thiamet-G.
28487326	3	105	theme	reticulum	532:540	arg1	sensor					549:554	the endoplasmic reticulum stress sensor	516:554	the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1)	516:584	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	3	105	theme	reticulum	532:540	arg1	enzyme-1					576:583	inositol-requiring enzyme-1	557:583	inositol-requiring enzyme-1	557:583	A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked β-N-acetylglucosamine) modification of proteins (O-GlcNAcylation).
28487326	1	106	theme	reticulum	241:249	arg1	dysfunction					251:261	endoplasmic reticulum dysfunction	229:261	endoplasmic reticulum dysfunction	229:261	BACKGROUND AND PURPOSE Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke.
31266872	7	0	theme	antibody	1443:1450	arg1	instance					1409:1416	the first instance	1399:1416	the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity	1399:1825	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	1	1	theme	immunodeficiency	282:297	arg1	type					305:308	human immunodeficiency virus type 1	276:310	human immunodeficiency virus type 1 (HIV-1)	276:318	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	1	theme	immunodeficiency	282:297	arg1	HIV-1					313:317	HIV-1	313:317	HIV-1	313:317	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	4	2	theme	SIVmac239	869:877	arg1	loop					861:864	the V2 loop	854:864	the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env	854:930	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody.
31266872	7	3	theme	HIV-1	1424:1428	arg1	antibody					1443:1450	an HIV-1 Env-specific antibody	1421:1450	an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity	1421:1825	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	3	4	theme	antibody-dependent	730:747	arg1	ADCC					772:775	ADCC	772:775	ADCC	772:775	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	3	4	theme	antibody-dependent	730:747	arg1	cytotoxicity					758:769	antibody-dependent cellular cytotoxicity	730:769	antibody-dependent cellular cytotoxicity (ADCC)	730:776	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	6	5	theme	binding	1283:1289	arg1	affinity					1264:1271	the affinity	1260:1271	the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers	1260:1362	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	8	6	theme	antibody	1954:1961	arg1	affinity					1971:1978	antibody binding affinity	1954:1978	antibody binding affinity	1954:1978	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	3	7	theme	neutralizing	605:616	arg1	antibody					618:625	a broadly neutralizing antibody	595:625	a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env	595:677	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	3	7	theme	neutralizing	605:616	arg1	PGT145					587:592	PGT145	587:592	PGT145	587:592	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	7	8	theme	SIV	1811:1813	arg1	infectivity					1815:1825	SIV infectivity	1811:1825	SIV infectivity	1811:1825	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	7	9	theme	first	1403:1407	arg1	instance					1409:1416	the first instance	1399:1416	the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity	1399:1825	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	6	10	theme	Env	1352:1354	arg1	trimers					1356:1362	soluble Env trimers	1344:1362	soluble Env trimers	1344:1362	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	7	11	dep	neutralization.IMPORTANCE	1602:1626	arg1	show					1636:1639	show	1636:1639	show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity	1636:1825	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	1	12	theme	evolutionary	224:235	arg1	origins					237:243	their independent evolutionary origins	206:243	their independent evolutionary origins in apes and Old World monkeys	206:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	3	13	theme	SIVsmm/mac	802:811	arg1	infectivity					813:823	SIVsmm/mac infectivity	802:823	SIVsmm/mac infectivity	802:823	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	0	14	theme	Cellular	143:150	arg1	Cytotoxicity					152:163	Antibody-Dependent Cellular Cytotoxicity	124:163	Antibody-Dependent Cellular Cytotoxicity	124:163	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	1	15	theme	distinct	425:432	arg1	consequence					191:201	a consequence	189:201	a consequence of their independent evolutionary origins in apes and Old World monkeys	189:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	15	theme	distinct	425:432	arg1	glycoproteins					443:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	3	16	theme	quaternary	632:641	arg1	epitope					643:649	a quaternary epitope	630:649	a quaternary epitope at the V2 apex of HIV-1 Env	630:677	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	1	17	from	origins	237:243	arg1	apes					248:251	apes	248:251	apes	248:251	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	17	from	origins	237:243	arg1	monkeys					267:273	Old World monkeys	257:273	Old World monkeys	257:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	4	18	theme	HIV-1	922:926	arg1	Env					928:930	HIV-1 Env	922:930	HIV-1 Env	922:930	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody.
31266872	1	19	from	apes	248:251	arg1	consequence					191:201	a consequence	189:201	a consequence of their independent evolutionary origins in apes and Old World monkeys	189:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	19	from	apes	248:251	arg1	glycoproteins					443:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	6	20	theme	cells	1331:1335	arg1	surface					1305:1311	the surface	1301:1311	the surface of virus-infected cells	1301:1335	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	6	21	from	increase	1248:1255	arg1	affinity					1264:1271	the affinity	1260:1271	the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers	1260:1362	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	3	22	theme	V2	658:659	arg1	apex					661:664	the V2 apex	654:664	the V2 apex of HIV-1 Env	654:677	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	4	23	from	substitutions	837:849	arg1	loop					861:864	the V2 loop	854:864	the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env	854:930	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody.
31266872	0	24	theme	V2	48:49	arg1	Antibody					65:72	an HIV-1 V2 Apex-Specific Antibody	39:72	an HIV-1 V2 Apex-Specific Antibody	39:72	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	1	25	theme	immunodeficiency	331:346	arg1	viruses					348:354	simian immunodeficiency viruses	324:354	simian immunodeficiency viruses of the SIVsmm/mac lineage	324:380	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	8	26	theme	first	1848:1852	arg1	instance					1854:1861	the first instance	1844:1861	the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env	1844:1935	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	7	27	theme	antibody-dependent	1746:1763	arg1	cytotoxicity					1774:1785	antibody-dependent cellular cytotoxicity	1746:1785	antibody-dependent cellular cytotoxicity	1746:1785	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	2	28	theme	Env	532:534	arg1	proteins					536:543	the Env proteins	528:543	the Env proteins of SIVsmm/mac isolates	528:566	Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/mac isolates.
31266872	0	29	theme	Antibody	65:72	arg1	Affinity					27:34	the Binding Affinity	15:34	the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein	15:113	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	4	30	from	epitope	900:906	arg1	Env					928:930	HIV-1 Env	922:930	HIV-1 Env	922:930	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody.
31266872	7	31	theme	cells	1737:1741	arg1	lysis					1715:1719	the lysis	1711:1719	the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity	1711:1785	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	0	32	from	Differences	0:10	arg1	Affinity					27:34	the Binding Affinity	15:34	the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein	15:113	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	1	33	theme	SIVsmm/mac	363:372	arg1	lineage					374:380	the SIVsmm/mac lineage	359:380	the SIVsmm/mac lineage	359:380	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	2	34	theme	isolates	559:566	arg1	proteins					536:543	the Env proteins	528:543	the Env proteins of SIVsmm/mac isolates	528:566	Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/mac isolates.
31266872	0	35	theme	Envelope	93:100	arg1	Glycoprotein					102:113	the SIVsmm/mac Envelope Glycoprotein	78:113	the SIVsmm/mac Envelope Glycoprotein	78:113	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	8	36	theme	HIV-1	1889:1893	arg1	antibody					1908:1915	an HIV-1 Env-specific antibody	1886:1915	an HIV-1 Env-specific antibody	1886:1915	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	5	37	theme	N-linked	1009:1016	arg1	N171Q					1038:1042	N171Q	1038:1042	N171Q	1038:1042	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	5	37	theme	N-linked	1009:1016	arg1	site					1032:1035	a conserved N-linked glycosylation site	997:1035	a conserved N-linked glycosylation site (N171Q)	997:1043	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	6	38	from	differences	1206:1216	arg1	function					1221:1228	function	1221:1228	function	1221:1228	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	1	39	theme	virus	299:303	arg1	type					305:308	human immunodeficiency virus type 1	276:310	human immunodeficiency virus type 1 (HIV-1)	276:318	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	39	theme	virus	299:303	arg1	HIV-1					313:317	HIV-1	313:317	HIV-1	313:317	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	8	40	theme	antibody	1908:1915	arg1	cross-reactivity					1866:1881	cross-reactivity	1866:1881	cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env	1866:1935	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	2	41	theme	Env-specific	470:481	arg1	antibodies					483:492	HIV-1 Env-specific antibodies	464:492	HIV-1 Env-specific antibodies	464:492	Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/mac isolates.
31266872	3	42	theme	Env	675:677	arg1	apex					661:664	the V2 apex	654:664	the V2 apex of HIV-1 Env	654:677	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	7	43	dep	potent	1656:1661	arg1	neutralizing					1671:1682	neutralizing	1671:1682	neutralizing	1671:1682	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	7	44	theme	binding	1534:1540	arg1	affinity					1542:1549	antibody binding affinity	1525:1549	antibody binding affinity for Env	1525:1557	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	4	45	theme	Amino	826:830	arg1	substitutions					837:849	Amino acid substitutions	826:849	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env	826:930	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody.
31266872	5	46	from	substitution	981:992	arg1	N171Q					1038:1042	N171Q	1038:1042	N171Q	1038:1042	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	5	46	from	substitution	981:992	arg1	site					1032:1035	a conserved N-linked glycosylation site	997:1035	a conserved N-linked glycosylation site (N171Q)	997:1043	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	1	47	theme	Old	257:259	arg1	monkeys					267:273	Old World monkeys	257:273	Old World monkeys	257:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	8	48	theme	SIVsmm/mac	1922:1931	arg1	Env					1933:1935	SIVsmm/mac Env	1922:1935	SIVsmm/mac Env	1922:1935	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	1	49	gly	glycoproteins	443:455	arg1	consequence					191:201	a consequence	189:201	a consequence of their independent evolutionary origins in apes and Old World monkeys	189:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	49	gly	glycoproteins	443:455	arg1	glycoproteins					443:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	8	50	theme	binding	1963:1969	arg1	affinity					1971:1978	antibody binding affinity	1954:1978	antibody binding affinity	1954:1978	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	3	51	from	apex	661:664	arg1	epitope					643:649	a quaternary epitope	630:649	a quaternary epitope at the V2 apex of HIV-1 Env	630:677	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	3	52	theme	SIVsmm/mac-infected	701:719	arg1	cells					721:725	SIVsmm/mac-infected cells	701:725	SIVsmm/mac-infected cells	701:725	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	1	53	theme	human	276:280	arg1	type					305:308	human immunodeficiency virus type 1	276:310	human immunodeficiency virus type 1 (HIV-1)	276:318	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	53	theme	human	276:280	arg1	HIV-1					313:317	HIV-1	313:317	HIV-1	313:317	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	5	54	link	N-linked	1009:1016	arg1	N171Q					1038:1042	N171Q	1038:1042	N171Q	1038:1042	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	5	54	link	N-linked	1009:1016	arg1	site					1032:1035	a conserved N-linked glycosylation site	997:1035	a conserved N-linked glycosylation site (N171Q)	997:1043	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	7	55	theme	SIVsmm/mac	1475:1484	arg1	Env					1486:1488	SIVsmm/mac Env	1475:1488	SIVsmm/mac Env	1475:1488	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	7	56	theme	Env-specific	1430:1441	arg1	antibody					1443:1450	an HIV-1 Env-specific antibody	1421:1450	an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity	1421:1825	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	3	57	theme	cellular	749:756	arg1	ADCC					772:775	ADCC	772:775	ADCC	772:775	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	3	57	theme	cellular	749:756	arg1	cytotoxicity					758:769	antibody-dependent cellular cytotoxicity	730:769	antibody-dependent cellular cytotoxicity (ADCC)	730:776	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	6	58	theme	PGT145	1276:1281	arg1	binding					1283:1289	PGT145 binding	1276:1289	PGT145 binding	1276:1289	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	3	59	theme	broadly	597:603	arg1	antibody					618:625	a broadly neutralizing antibody	595:625	a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env	595:677	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	3	59	theme	broadly	597:603	arg1	PGT145					587:592	PGT145	587:592	PGT145	587:592	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	0	60	theme	Antibody-Dependent	124:141	arg1	Cytotoxicity					152:163	Antibody-Dependent Cellular Cytotoxicity	124:163	Antibody-Dependent Cellular Cytotoxicity	124:163	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	1	61	theme	independent	212:222	arg1	origins					237:243	their independent evolutionary origins	206:243	their independent evolutionary origins in apes and Old World monkeys	206:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	7	62	theme	potent	1656:1661	arg1	PGT145					1646:1651	PGT145	1646:1651	PGT145	1646:1651	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	7	62	theme	potent	1656:1661	arg1	antibody					1684:1691	a potent broadly neutralizing antibody	1654:1691	a potent broadly neutralizing antibody to HIV-1	1654:1700	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	6	63	theme	soluble	1344:1350	arg1	trimers					1356:1362	soluble Env trimers	1344:1362	soluble Env trimers	1344:1362	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	1	64	theme	origins	237:243	arg1	consequence					191:201	a consequence	189:201	a consequence of their independent evolutionary origins in apes and Old World monkeys	189:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	64	theme	origins	237:243	arg1	glycoproteins					443:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	65	theme	envelope	434:441	arg1	consequence					191:201	a consequence	189:201	a consequence of their independent evolutionary origins in apes and Old World monkeys	189:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	65	theme	envelope	434:441	arg1	glycoproteins					443:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	7	66	from	differences	1510:1520	arg1	affinity					1542:1549	antibody binding affinity	1525:1549	antibody binding affinity for Env	1525:1557	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	6	67	theme	virus-infected	1316:1329	arg1	cells					1331:1335	virus-infected cells	1316:1335	virus-infected cells	1316:1335	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	0	68	theme	Apex-Specific	51:63	arg1	Antibody					65:72	an HIV-1 V2 Apex-Specific Antibody	39:72	an HIV-1 V2 Apex-Specific Antibody	39:72	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	5	69	theme	lysine-to-serine	1079:1094	arg1	K180S					1125:1129	K180S	1125:1129	K180S	1125:1129	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	5	69	theme	lysine-to-serine	1079:1094	arg1	substitution					1096:1107	a lysine-to-serine substitution	1077:1107	a lysine-to-serine substitution in this region (K180S)	1077:1130	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	1	70	from	consequence	191:201	arg1	apes					248:251	apes	248:251	apes	248:251	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	70	from	consequence	191:201	arg1	monkeys					267:273	Old World monkeys	257:273	Old World monkeys	257:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	7	71	theme	cellular	1765:1772	arg1	cytotoxicity					1774:1785	antibody-dependent cellular cytotoxicity	1746:1785	antibody-dependent cellular cytotoxicity	1746:1785	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	0	72	theme	SIVsmm/mac	82:91	arg1	Glycoprotein					102:113	the SIVsmm/mac Envelope Glycoprotein	78:113	the SIVsmm/mac Envelope Glycoprotein	78:113	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	5	73	from	substitution	1096:1107	arg1	region					1117:1122	this region	1112:1122	this region	1112:1122	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	1	74	theme	lineage	374:380	arg1	type					305:308	human immunodeficiency virus type 1	276:310	human immunodeficiency virus type 1 (HIV-1)	276:318	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	74	theme	lineage	374:380	arg1	HIV-1					313:317	HIV-1	313:317	HIV-1	313:317	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	74	theme	lineage	374:380	arg1	viruses					348:354	simian immunodeficiency viruses	324:354	simian immunodeficiency viruses of the SIVsmm/mac lineage	324:380	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	8	75	theme	cross-reactivity	1866:1881	arg1	instance					1854:1861	the first instance	1844:1861	the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env	1844:1935	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	5	76	theme	conserved	999:1007	arg1	N171Q					1038:1042	N171Q	1038:1042	N171Q	1038:1042	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	5	76	theme	conserved	999:1007	arg1	site					1032:1035	a conserved N-linked glycosylation site	997:1035	a conserved N-linked glycosylation site (N171Q)	997:1043	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	7	77	theme	SIV-infected	1724:1735	arg1	cells					1737:1741	SIV-infected cells	1724:1741	SIV-infected cells	1724:1741	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	2	78	theme	SIVsmm/mac	548:557	arg1	isolates					559:566	SIVsmm/mac isolates	548:566	SIVsmm/mac isolates	548:566	Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/mac isolates.
31266872	1	79	from	monkeys	267:273	arg1	consequence					191:201	a consequence	189:201	a consequence of their independent evolutionary origins in apes and Old World monkeys	189:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	1	79	from	monkeys	267:273	arg1	glycoproteins					443:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	phylogenetically and antigenically distinct envelope glycoproteins	390:455	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	0	80	theme	Binding	19:25	arg1	Affinity					27:34	the Binding Affinity	15:34	the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein	15:113	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	8	81	theme	Env-specific	1895:1906	arg1	antibody					1908:1915	an HIV-1 Env-specific antibody	1886:1915	an HIV-1 Env-specific antibody	1886:1915	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	2	82	theme	HIV-1	464:468	arg1	antibodies					483:492	HIV-1 Env-specific antibodies	464:492	HIV-1 Env-specific antibodies	464:492	Thus, HIV-1 Env-specific antibodies do not typically cross-react with the Env proteins of SIVsmm/mac isolates.
31266872	3	83	theme	HIV-1	669:673	arg1	Env					675:677	HIV-1 Env	669:677	HIV-1 Env	669:677	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	5	84	gly	glycosylation	1018:1030	arg2	N171Q					1038:1042	N171Q	1038:1042	N171Q	1038:1042	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	5	84	gly	glycosylation	1018:1030	arg2	site					1032:1035	a conserved N-linked glycosylation site	997:1035	a conserved N-linked glycosylation site (N171Q)	997:1043	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	0	85	theme	HIV-1	42:46	arg1	Antibody					65:72	an HIV-1 V2 Apex-Specific Antibody	39:72	an HIV-1 V2 Apex-Specific Antibody	39:72	Differences in the Binding Affinity of an HIV-1 V2 Apex-Specific Antibody for the SIVsmm/mac Envelope Glycoprotein Uncouple Antibody-Dependent Cellular Cytotoxicity from Neutralization.
31266872	5	86	theme	susceptible	1169:1179	arg1	virus					1163:1167	the virus	1159:1167	the virus susceptible to neutralization	1159:1197	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	4	87	theme	V2	858:859	arg1	loop					861:864	the V2 loop	854:864	the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env	854:930	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody.
31266872	1	88	theme	simian	324:329	arg1	viruses					348:354	simian immunodeficiency viruses	324:354	simian immunodeficiency viruses of the SIVsmm/mac lineage	324:380	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31266872	5	89	theme	glycosylation	1018:1030	arg1	N171Q					1038:1042	N171Q	1038:1042	N171Q	1038:1042	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	5	89	theme	glycosylation	1018:1030	arg1	site					1032:1035	a conserved N-linked glycosylation site	997:1035	a conserved N-linked glycosylation site (N171Q)	997:1043	Whereas a substitution in a conserved N-linked glycosylation site (N171Q) eliminates sensitivity to ADCC, a lysine-to-serine substitution in this region (K180S) increases ADCC and renders the virus susceptible to neutralization.
31266872	6	90	from	Env	1294:1296	arg1	surface					1305:1311	the surface	1301:1311	the surface of virus-infected cells	1301:1335	These differences in function correlate with an increase in the affinity of PGT145 binding to Env on the surface of virus-infected cells and to soluble Env trimers.
31266872	7	91	theme	antibody	1525:1532	arg1	affinity					1542:1549	antibody binding affinity	1525:1549	antibody binding affinity for Env	1525:1557	To our knowledge, this represents the first instance of an HIV-1 Env-specific antibody that cross-reacts with SIVsmm/mac Env and illustrates how differences in antibody binding affinity for Env can differentiate sensitivity to ADCC from neutralization.IMPORTANCE Here we show that PGT145, a potent broadly neutralizing antibody to HIV-1, directs the lysis of SIV-infected cells by antibody-dependent cellular cytotoxicity but does not neutralize SIV infectivity.
31266872	8	92	with	cross-reactivity	1866:1881	arg1	Env					1933:1935	SIVsmm/mac Env	1922:1935	SIVsmm/mac Env	1922:1935	This represents the first instance of cross-reactivity of an HIV-1 Env-specific antibody with SIVsmm/mac Env and reveals that antibody binding affinity can differentiate sensitivity to ADCC from neutralization.
31266872	3	93	theme	cells	721:725	arg1	lysis					692:696	the lysis	688:696	the lysis of SIVsmm/mac-infected cells	688:725	Here we show that PGT145, a broadly neutralizing antibody to a quaternary epitope at the V2 apex of HIV-1 Env, directs the lysis of SIVsmm/mac-infected cells by antibody-dependent cellular cytotoxicity (ADCC) but does not neutralize SIVsmm/mac infectivity.
31266872	4	94	theme	acid	832:835	arg1	substitutions					837:849	Amino acid substitutions	826:849	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env	826:930	Amino acid substitutions in the V2 loop of SIVmac239 corresponding to the epitope for PGT145 in HIV-1 Env modulate sensitivity to this antibody.
31266872	1	95	theme	World	261:265	arg1	monkeys					267:273	Old World monkeys	257:273	Old World monkeys	257:273	As a consequence of their independent evolutionary origins in apes and Old World monkeys, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency viruses of the SIVsmm/mac lineage express phylogenetically and antigenically distinct envelope glycoproteins.
31194940	0	0	theme	Neutralizing	89:100	arg1	Antibodies					102:111	Broadly Neutralizing Antibodies	81:111	Broadly Neutralizing Antibodies	81:111	Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies.
31194940	1	1	theme	envelope	147:154	arg1	Env					170:172	Env	170:172	Env	170:172	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	1	1	theme	envelope	147:154	arg1	glycoprotein					156:167	HIV-1 envelope glycoprotein	141:167	HIV-1 envelope glycoprotein (Env)	141:173	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	0	2	theme	Broadly	81:87	arg1	Antibodies					102:111	Broadly Neutralizing Antibodies	81:111	Broadly Neutralizing Antibodies	81:111	Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies.
31194940	0	3	from	Plasticity	15:24	arg1	Peptide					46:52	the HIV-1 Fusion Peptide	29:52	the HIV-1 Fusion Peptide	29:52	Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies.
31194940	1	4	theme	glycoprotein	156:167	arg1	FP					134:135	FP	134:135	FP	134:135	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	1	4	theme	glycoprotein	156:167	arg1	peptide					125:131	The fusion peptide	114:131	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env)	114:173	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	1	4	theme	glycoprotein	156:167	arg1	essential					178:186	essential	178:186	essential	178:186	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	3	5	attach	derived	524:530	arg1	patient					546:552	the same patient	537:552	the same patient	537:552	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	3	5	attach	derived	524:530	arg2	AMC011					505:510	AMC011 SOSIP.v4.2	505:521	AMC011 SOSIP.v4.2	505:521	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	3	5	attach	derived	524:530	arg2	trimer					497:502	a soluble Env trimer	483:502	a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient	483:552	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	5	6	with	VRC34.01	793:800	arg1	AMC011					807:812	AMC011 SOSIP.v4.2	807:823	AMC011 SOSIP.v4.2	807:823	A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP.
31194940	3	7	theme	soluble	485:491	arg1	AMC011					505:510	AMC011 SOSIP.v4.2	505:521	AMC011 SOSIP.v4.2	505:521	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	3	7	theme	soluble	485:491	arg1	trimer					497:502	a soluble Env trimer	483:502	a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient	483:552	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	3	8	theme	Env	493:495	arg1	AMC011					505:510	AMC011 SOSIP.v4.2	505:521	AMC011 SOSIP.v4.2	505:521	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	3	8	theme	Env	493:495	arg1	trimer					497:502	a soluble Env trimer	483:502	a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient	483:552	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	4	9	theme	hydrophobic	629:639	arg1	FP					641:642	the exposed hydrophobic FP	617:642	the exposed hydrophobic FP	617:642	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	4	10	with	interaction	600:610	arg1	FP					641:642	the exposed hydrophobic FP	617:642	the exposed hydrophobic FP	617:642	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	6	11	theme	different	946:954	arg1	conformations					956:968	different conformations	946:968	different conformations	946:968	We further demonstrate that the FP can twist and present different conformations for recognition by bnAbs, which enables approach to Env from diverse angles.
31194940	5	12	theme	identified	777:786	arg1	VRC34.01					793:800	another previously identified bnAb VRC34.01	758:800	another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2	758:823	A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP.
31194940	4	13	theme	N-linked	711:718	arg1	glycan					720:725	a conserved N-linked glycan	699:725	a conserved N-linked glycan at N88	699:732	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	4	14	theme	gp120	682:686	arg1	region					672:677	a continuous region	659:677	a continuous region	659:677	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	3	15	theme	bnAb	410:413	arg1	structures					396:405	X-ray and cryo-electron microscopy (cryo-EM) structures	351:405	X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202	351:420	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	3	16	theme	X-ray	351:355	arg1	structures					396:405	X-ray and cryo-electron microscopy (cryo-EM) structures	351:405	X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202	351:420	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	7	17	theme	vaccine	1114:1120	arg1	design					1122:1127	vaccine design	1114:1127	vaccine design	1114:1127	The variable recognition of FP by bnAbs thus provides insights for vaccine design.
31194940	7	18	theme	FP	1075:1076	arg1	recognition					1060:1070	The variable recognition	1047:1070	The variable recognition of FP by bnAbs	1047:1085	The variable recognition of FP by bnAbs thus provides insights for vaccine design.
31194940	4	19	theme	β	590:590	arg1	interaction					600:610	a "β strand" interaction	587:610	a "β strand" interaction with the exposed hydrophobic FP	587:642	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	0	20	theme	Conformational	0:13	arg1	Plasticity					15:24	Conformational Plasticity	0:24	Conformational Plasticity in the HIV-1 Fusion Peptide	0:52	Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies.
31194940	4	21	theme	"	589:589	arg1	interaction					600:610	a "β strand" interaction	587:610	a "β strand" interaction with the exposed hydrophobic FP	587:642	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	3	22	theme	same	541:544	arg1	patient					546:552	the same patient	537:552	the same patient	537:552	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	4	23	theme	continuous	661:670	arg1	region					672:677	a continuous region	659:677	a continuous region	659:677	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	4	24	link	N-linked	711:718	arg1	glycan					720:725	a conserved N-linked glycan	699:725	a conserved N-linked glycan at N88	699:732	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	1	25	theme	fusion	118:123	arg1	FP					134:135	FP	134:135	FP	134:135	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	1	25	theme	fusion	118:123	arg1	peptide					125:131	The fusion peptide	114:131	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env)	114:173	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	1	25	theme	fusion	118:123	arg1	essential					178:186	essential	178:186	essential	178:186	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	5	26	theme	cryo-EM	737:743	arg1	structure					745:753	A cryo-EM structure	735:753	A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2	735:823	A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP.
31194940	0	27	theme	Fusion	39:44	arg1	Peptide					46:52	the HIV-1 Fusion Peptide	29:52	the HIV-1 Fusion Peptide	29:52	Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies.
31194940	5	28	theme	bnAb	788:791	arg1	VRC34.01					793:800	another previously identified bnAb VRC34.01	758:800	another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2	758:823	A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP.
31194940	0	29	theme	HIV-1	33:37	arg1	Peptide					46:52	the HIV-1 Fusion Peptide	29:52	the HIV-1 Fusion Peptide	29:52	Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies.
31194940	7	30	theme	variable	1051:1058	arg1	recognition					1060:1070	The variable recognition	1047:1070	The variable recognition of FP by bnAbs	1047:1085	The variable recognition of FP by bnAbs thus provides insights for vaccine design.
31194940	1	31	theme	viral	202:206	arg1	entry					208:212	viral entry	202:212	viral entry	202:212	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	3	32	theme	cryo-electron	361:373	arg1	microscopy					375:384	cryo-electron microscopy	361:384	cryo-electron microscopy (cryo-EM)	361:394	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	3	32	theme	cryo-electron	361:373	arg1	cryo-EM					387:393	cryo-EM	387:393	cryo-EM	387:393	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	5	33	theme	VRC34.01	793:800	arg1	structure					745:753	A cryo-EM structure	735:753	A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2	735:823	A cryo-EM structure of another previously identified bnAb VRC34.01 with AMC011 SOSIP.v4.2 shows that it also penetrates through glycans to target the FP.
31194940	4	34	from	N88	730:732	arg1	glycan					720:725	a conserved N-linked glycan	699:725	a conserved N-linked glycan at N88	699:732	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	4	35	theme	exposed	621:627	arg1	FP					641:642	the exposed hydrophobic FP	617:642	the exposed hydrophobic FP	617:642	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	3	36	theme	microscopy	375:384	arg1	structures					396:405	X-ray and cryo-electron microscopy (cryo-EM) structures	351:405	X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202	351:420	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	1	37	theme	HIV-1	141:145	arg1	Env					170:172	Env	170:172	Env	170:172	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	1	37	theme	HIV-1	141:145	arg1	glycoprotein					156:167	HIV-1 envelope glycoprotein	141:167	HIV-1 envelope glycoprotein (Env)	141:173	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	4	38	theme	conserved	701:709	arg1	glycan					720:725	a conserved N-linked glycan	699:725	a conserved N-linked glycan at N88	699:732	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	1	39	gly	glycoprotein	156:167	arg1	Env					170:172	Env	170:172	Env	170:172	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	1	39	gly	glycoprotein	156:167	arg1	glycoprotein					156:167	HIV-1 envelope glycoprotein	141:167	HIV-1 envelope glycoprotein (Env)	141:173	The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry.
31194940	4	40	theme	strand	592:597	arg1	interaction					600:610	a "β strand" interaction	587:610	a "β strand" interaction with the exposed hydrophobic FP	587:642	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	3	41	theme	HIV-infected	431:442	arg1	neutralizer					450:460	an HIV-infected elite neutralizer	428:460	an HIV-infected elite neutralizer	428:460	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	2	42	theme	antibodies	249:258	arg1	Detection					215:223	Detection	215:223	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP	215:292	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
31194940	3	43	theme	elite	444:448	arg1	neutralizer					450:460	an HIV-infected elite neutralizer	428:460	an HIV-infected elite neutralizer	428:460	We delineate X-ray and cryo-electron microscopy (cryo-EM) structures of bnAb ACS202, from an HIV-infected elite neutralizer, with an FP and with a soluble Env trimer (AMC011 SOSIP.v4.2) derived from the same patient.
31194940	6	44	theme	diverse	1031:1037	arg1	angles					1039:1044	diverse angles	1031:1044	diverse angles	1031:1044	We further demonstrate that the FP can twist and present different conformations for recognition by bnAbs, which enables approach to Env from diverse angles.
31194940	4	45	theme	ACS202	568:573	arg1	CDRH3					575:579	ACS202 CDRH3	568:579	ACS202 CDRH3	568:579	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	2	46	theme	neutralizing	236:247	arg1	bnAbs					261:265	bnAbs	261:265	bnAbs	261:265	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
31194940	2	46	theme	neutralizing	236:247	arg1	antibodies					249:258	broadly neutralizing antibodies	228:258	broadly neutralizing antibodies (bnAbs) that interact with the FP	228:292	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
31194940	4	47	theme	"	598:598	arg1	interaction					600:610	a "β strand" interaction	587:610	a "β strand" interaction with the exposed hydrophobic FP	587:642	We show that ACS202 CDRH3 forms a "β strand" interaction with the exposed hydrophobic FP and recognizes a continuous region of gp120, including a conserved N-linked glycan at N88.
31194940	2	48	theme	broadly	228:234	arg1	bnAbs					261:265	bnAbs	261:265	bnAbs	261:265	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
31194940	2	48	theme	broadly	228:234	arg1	antibodies					249:258	broadly neutralizing antibodies	228:258	broadly neutralizing antibodies (bnAbs) that interact with the FP	228:292	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
31194940	2	49	theme	vulnerability	323:335	arg1	vulnerability					323:335	vulnerability	323:335	vulnerability	323:335	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
31194940	2	49	theme	vulnerability	323:335	arg1	it					307:308	it	307:308	it	307:308	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
31194940	2	49	theme	vulnerability	323:335	arg1	site					315:318	a site	313:318	a site of vulnerability	313:335	Detection of broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site of vulnerability.
30677534	2	0	from	piglets	526:532	arg1	cities					554:559	cities	554:559	cities	554:559	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	2	0	from	piglets	526:532	arg1	provinces					540:548	10 provinces	537:548	10 provinces	537:548	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	1	1	theme	virulent	233:240	arg1	PEDV					275:278	PEDV	275:278	PEDV	275:278	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	1	1	theme	virulent	233:240	arg1	virus					268:272	the highly virulent porcine epidemic diarrhea virus	222:272	the highly virulent porcine epidemic diarrhea virus (PEDV) variants	222:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	9	2	theme	PEDV	1803:1806	arg1	isolates					1808:1815	the emerging PEDV isolates	1790:1815	the emerging PEDV isolates of China	1790:1824	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	5	3	from	homology	1051:1058	arg1	protein					1069:1075	the S protein	1063:1075	the S protein	1063:1075	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	8	4	theme	delayed	1615:1621	arg1	onset					1623:1627	a slightly delayed onset	1604:1627	a slightly delayed onset	1604:1627	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	1	5	theme	epidemic	250:257	arg1	PEDV					275:278	PEDV	275:278	PEDV	275:278	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	1	5	theme	epidemic	250:257	arg1	virus					268:272	the highly virulent porcine epidemic diarrhea virus	222:272	the highly virulent porcine epidemic diarrhea virus (PEDV) variants	222:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	4	6	theme	amino	803:807	arg1	mutations					814:822	103-120 amino acid mutations	795:822	103-120 amino acid mutations	795:822	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	8	7	theme	intramuscular	1531:1543	arg1	infection					1545:1553	intramuscular infection	1531:1553	intramuscular infection	1531:1553	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	0	8	theme	Genetic	0:6	arg1	analysis					18:25	Genetic evolution analysis	0:25	Genetic evolution analysis	0:25	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	5	9	theme	S	1067:1067	arg1	protein					1069:1075	the S protein	1063:1075	the S protein	1063:1075	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	10	10	theme	etiological	2006:2016	arg1	characteristics					2018:2032	the etiological characteristics	2002:2032	the etiological characteristics of the epidemic PEDV isolates	2002:2062	This study shows the necessity of monitoring the molecular epidemiology and the etiological characteristics of the epidemic PEDV isolates, which may help better control the PED outbreaks.
30677534	1	11	theme	porcine	180:186	arg1	diarrhea					197:204	porcine epidemic diarrhea	180:204	porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants	180:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	1	11	theme	porcine	180:186	arg1	PED					207:209	PED	207:209	PED	207:209	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	10	12	theme	isolates	2055:2062	arg1	epidemiology					1985:1996	the molecular epidemiology	1971:1996	the molecular epidemiology	1971:1996	This study shows the necessity of monitoring the molecular epidemiology and the etiological characteristics of the epidemic PEDV isolates, which may help better control the PED outbreaks.
30677534	10	12	theme	isolates	2055:2062	arg1	characteristics					2018:2032	the etiological characteristics	2002:2032	the etiological characteristics of the epidemic PEDV isolates	2002:2062	This study shows the necessity of monitoring the molecular epidemiology and the etiological characteristics of the epidemic PEDV isolates, which may help better control the PED outbreaks.
30677534	3	13	theme	circulating	700:710	arg1	strains					712:718	the current circulating strains	688:718	the current circulating strains	688:718	The phylogenetic analysis indicated that all the 15 PEDV isolates clustered into G2 genotype associated with the current circulating strains.
30677534	0	14	theme	China	122:126	arg1	part					114:117	part	114:117	part of China	114:126	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	8	15	theme	variant	1650:1656	arg1	FJzz1					1671:1675	the variant PEDV isolate FJzz1	1646:1675	the variant PEDV isolate FJzz1	1646:1675	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	8	15	theme	variant	1650:1656	arg1	pathogenic					1688:1697	pathogenic	1688:1697	pathogenic	1688:1697	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	1	16	theme	diarrhea	197:204	arg1	outbreaks					167:175	the outbreaks	163:175	the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants	163:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	4	17	theme	N	871:871	arg1	S1					892:893	S1	892:893	S1 (S1-NTD)	892:902	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	4	17	theme	N	871:871	arg1	domain					882:887	the N terminal domain	867:887	the N terminal domain of S1 (S1-NTD)	867:902	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	9	18	theme	variant	1846:1852	arg1	PEDV					1854:1857	G2 variant PEDV	1843:1857	G2 variant PEDV	1843:1857	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	5	19	theme	other	1095:1099	arg1	strains					1119:1125	the other original pandemic strains	1091:1125	the other original pandemic strains	1091:1125	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	1	20	theme	pork	364:367	arg1	industry					369:376	the pork industry	360:376	the pork industry	360:376	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	8	21	theme	isolate	1663:1669	arg1	FJzz1					1671:1675	the variant PEDV isolate FJzz1	1646:1675	the variant PEDV isolate FJzz1	1646:1675	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	8	21	theme	isolate	1663:1669	arg1	pathogenic					1688:1697	pathogenic	1688:1697	pathogenic	1688:1697	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	6	22	theme	altered	1332:1338	arg1	pathogenicity					1340:1352	the altered pathogenicity	1328:1352	the altered pathogenicity of these variant PEDV strains	1328:1382	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	2	23	theme	piglets	526:532	arg1	samples					505:511	fecal samples	499:511	fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	499:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	5	24	theme	original	1101:1108	arg1	strains					1119:1125	the other original pandemic strains	1091:1125	the other original pandemic strains	1091:1125	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	3	25	theme	phylogenetic	583:594	arg1	analysis					596:603	The phylogenetic analysis	579:603	The phylogenetic analysis	579:603	The phylogenetic analysis indicated that all the 15 PEDV isolates clustered into G2 genotype associated with the current circulating strains.
30677534	2	26	theme	representative	452:465	arg1	strains					467:473	15 PEDV representative strains	444:473	15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	444:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	10	27	theme	molecular	1975:1983	arg1	epidemiology					1985:1996	the molecular epidemiology	1971:1996	the molecular epidemiology	1971:1996	This study shows the necessity of monitoring the molecular epidemiology and the etiological characteristics of the epidemic PEDV isolates, which may help better control the PED outbreaks.
30677534	9	28	theme	prevalent	1879:1887	arg1	strains					1889:1895	the main prevalent strains	1870:1895	the main prevalent strains that may mutate continually	1870:1923	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	6	29	theme	S1-NTD	1291:1296	arg1	S1-NTD					1291:1296	S1-NTD	1291:1296	S1-NTD	1291:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	29	theme	S1-NTD	1291:1296	arg1	sites					1282:1286	asparagine (N)-linked glycosylation sites	1246:1286	asparagine (N)-linked glycosylation sites of S1-NTD	1246:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	29	theme	S1-NTD	1291:1296	arg1	structure					1232:1240	conformational structure	1217:1240	conformational structure	1217:1240	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	8	30	theme	suckling	1702:1709	arg1	piglets					1711:1717	suckling piglets	1702:1717	suckling piglets	1702:1717	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	1	31	theme	recent	149:154	arg1	years					156:160	recent years	149:160	recent years	149:160	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	7	32	theme	infection	1483:1491	arg1	routes					1493:1498	oral and intramuscular infection routes	1460:1498	oral and intramuscular infection routes	1460:1498	We evaluated the pathogenicity of the PEDV strain FJzz1 in piglets through oral and intramuscular infection routes.
30677534	0	33	theme	virus	85:89	arg1	strains					91:97	porcine epidemic diarrhea virus strains	59:97	porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017	59:143	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	5	34	theme	%	1038:1038	arg1	homology					1051:1058	96.3-99.8% amino acid homology	1029:1058	96.3-99.8% amino acid homology in the S protein	1029:1075	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	6	35	theme	-linked	1260:1266	arg1	S1-NTD					1291:1296	S1-NTD	1291:1296	S1-NTD	1291:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	35	theme	-linked	1260:1266	arg1	sites					1282:1286	asparagine (N)-linked glycosylation sites	1246:1286	asparagine (N)-linked glycosylation sites of S1-NTD	1246:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	5	36	theme	96.9-99.7	994:1002	arg1	%					1003:1003	%	1003:1003	%	1003:1003	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	4	37	theme	S1	892:893	arg1	S1					892:893	S1	892:893	S1 (S1-NTD)	892:902	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	4	37	theme	S1	892:893	arg1	domain					882:887	the N terminal domain	867:887	the N terminal domain of S1 (S1-NTD)	867:902	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	5	38	theme	pandemic	1110:1117	arg1	strains					1119:1125	the other original pandemic strains	1091:1125	the other original pandemic strains	1091:1125	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	1	39	theme	economic	340:347	arg1	impacts					349:355	severe economic impacts	333:355	severe economic impacts to the pork industry	333:376	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	8	40	theme	oral	1515:1518	arg1	infection					1520:1528	oral infection	1515:1528	oral infection	1515:1528	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	5	41	from	homology	1016:1023	arg1	protein					1069:1075	the S protein	1063:1075	the S protein	1063:1075	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	1	42	theme	diarrhea	259:266	arg1	PEDV					275:278	PEDV	275:278	PEDV	275:278	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	1	42	theme	diarrhea	259:266	arg1	virus					268:272	the highly virulent porcine epidemic diarrhea virus	222:272	the highly virulent porcine epidemic diarrhea virus (PEDV) variants	222:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	2	43	from	provinces	540:548	arg1	samples					505:511	fecal samples	499:511	fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	499:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	6	44	link	-linked	1260:1266	arg1	S1-NTD					1291:1296	S1-NTD	1291:1296	S1-NTD	1291:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	44	link	-linked	1260:1266	arg1	sites					1282:1286	asparagine (N)-linked glycosylation sites	1246:1286	asparagine (N)-linked glycosylation sites of S1-NTD	1246:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	10	45	theme	PED	2099:2101	arg1	outbreaks					2103:2111	the PED outbreaks	2095:2111	the PED outbreaks	2095:2111	This study shows the necessity of monitoring the molecular epidemiology and the etiological characteristics of the epidemic PEDV isolates, which may help better control the PED outbreaks.
30677534	7	46	theme	FJzz1	1435:1439	arg1	pathogenicity					1402:1414	the pathogenicity	1398:1414	the pathogenicity of the PEDV strain FJzz1 in piglets	1398:1450	We evaluated the pathogenicity of the PEDV strain FJzz1 in piglets through oral and intramuscular infection routes.
30677534	2	47	from	cities	554:559	arg1	samples					505:511	fecal samples	499:511	fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	499:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	0	48	theme	pathogenicity	31:43	arg1	assessment					45:54	pathogenicity assessment	31:54	pathogenicity assessment	31:54	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	5	49	theme	acid	1046:1049	arg1	homology					1051:1058	96.3-99.8% amino acid homology	1029:1058	96.3-99.8% amino acid homology in the S protein	1029:1075	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	7	50	theme	PEDV	1423:1426	arg1	FJzz1					1435:1439	the PEDV strain FJzz1	1419:1439	the PEDV strain FJzz1	1419:1439	We evaluated the pathogenicity of the PEDV strain FJzz1 in piglets through oral and intramuscular infection routes.
30677534	6	51	gly	glycosylation	1268:1280	arg2	S1-NTD					1291:1296	S1-NTD	1291:1296	S1-NTD	1291:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	51	gly	glycosylation	1268:1280	arg1	S1-NTD					1291:1296	S1-NTD	1291:1296	S1-NTD	1291:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	51	gly	glycosylation	1268:1280	arg2	sites					1282:1286	asparagine (N)-linked glycosylation sites	1246:1286	asparagine (N)-linked glycosylation sites of S1-NTD	1246:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	0	52	theme	epidemic	67:74	arg1	strains					91:97	porcine epidemic diarrhea virus strains	59:97	porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017	59:143	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	9	53	theme	genetic	1751:1757	arg1	variation					1759:1767	the genetic variation	1747:1767	the genetic variation	1747:1767	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	4	54	theme	prototype	753:761	arg1	strain					763:768	the prototype strain CV777	749:774	the prototype strain CV777	749:774	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	8	55	theme	typical	1572:1578	arg1	signs					1589:1593	typical clinical signs	1572:1593	typical clinical signs	1572:1593	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	7	56	from	pathogenicity	1402:1414	arg1	piglets					1444:1450	piglets	1444:1450	piglets	1444:1450	We evaluated the pathogenicity of the PEDV strain FJzz1 in piglets through oral and intramuscular infection routes.
30677534	2	57	from	samples	505:511	arg1	cities					554:559	cities	554:559	cities	554:559	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	2	57	from	samples	505:511	arg1	provinces					540:548	10 provinces	537:548	10 provinces	537:548	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	6	58	theme	remarkable	1191:1200	arg1	changes					1202:1208	remarkable changes	1191:1208	remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains	1191:1382	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	59	theme	variant	1363:1369	arg1	strains					1376:1382	these variant PEDV strains	1357:1382	these variant PEDV strains	1357:1382	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	9	60	theme	emerging	1794:1801	arg1	isolates					1808:1815	the emerging PEDV isolates	1790:1815	the emerging PEDV isolates of China	1790:1824	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	1	61	theme	porcine	242:248	arg1	PEDV					275:278	PEDV	275:278	PEDV	275:278	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	1	61	theme	porcine	242:248	arg1	virus					268:272	the highly virulent porcine epidemic diarrhea virus	222:272	the highly virulent porcine epidemic diarrhea virus (PEDV) variants	222:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	4	62	theme	S	833:833	arg1	proteins					835:842	their S proteins	827:842	their S proteins	827:842	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	9	63	theme	isolates	1808:1815	arg1	pathogenicity					1773:1785	pathogenicity	1773:1785	pathogenicity	1773:1785	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	9	63	theme	isolates	1808:1815	arg1	variation					1759:1767	the genetic variation	1747:1767	the genetic variation	1747:1767	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	3	64	theme	current	692:698	arg1	strains					712:718	the current circulating strains	688:718	the current circulating strains	688:718	The phylogenetic analysis indicated that all the 15 PEDV isolates clustered into G2 genotype associated with the current circulating strains.
30677534	9	65	theme	China	1820:1824	arg1	isolates					1808:1815	the emerging PEDV isolates	1790:1815	the emerging PEDV isolates of China	1790:1824	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	4	66	theme	acid	809:812	arg1	mutations					814:822	103-120 amino acid mutations	795:822	103-120 amino acid mutations	795:822	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	1	67	theme	epidemic	188:195	arg1	diarrhea					197:204	porcine epidemic diarrhea	180:204	porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants	180:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	1	67	theme	epidemic	188:195	arg1	PED					207:209	PED	207:209	PED	207:209	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	9	68	theme	G2	1843:1844	arg1	PEDV					1854:1857	G2 variant PEDV	1843:1857	G2 variant PEDV	1843:1857	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	5	69	from	mutations	929:937	arg1	strains					955:961	all these 15 strains	942:961	all these 15 strains	942:961	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	6	70	dep	structure	1232:1240	arg1	the					1213:1215	the	1213:1215	the	1213:1215	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	71	theme	Computational	1128:1140	arg1	analysis					1142:1149	Computational analysis	1128:1149	Computational analysis	1128:1149	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	72	theme	conformational	1217:1230	arg1	structure					1232:1240	conformational structure	1217:1240	conformational structure	1217:1240	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	8	73	theme	PEDV	1658:1661	arg1	FJzz1					1671:1675	the variant PEDV isolate FJzz1	1646:1675	the variant PEDV isolate FJzz1	1646:1675	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	8	73	theme	PEDV	1658:1661	arg1	pathogenic					1688:1697	pathogenic	1688:1697	pathogenic	1688:1697	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	2	74	theme	diarrheic	516:524	arg1	piglets					526:532	diarrheic piglets	516:532	diarrheic piglets in 10 provinces and cities during 2011-2017	516:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	9	75	theme	main	1874:1877	arg1	strains					1889:1895	the main prevalent strains	1870:1895	the main prevalent strains that may mutate continually	1870:1923	In conclusion, we analyzed the genetic variation and pathogenicity of the emerging PEDV isolates of China, indicating that G2 variant PEDV strains as the main prevalent strains that may mutate continually.
30677534	0	76	theme	diarrhea	76:83	arg1	strains					91:97	porcine epidemic diarrhea virus strains	59:97	porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017	59:143	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	7	77	theme	intramuscular	1469:1481	arg1	routes					1493:1498	oral and intramuscular infection routes	1460:1498	oral and intramuscular infection routes	1460:1498	We evaluated the pathogenicity of the PEDV strain FJzz1 in piglets through oral and intramuscular infection routes.
30677534	2	78	theme	PEDV	447:450	arg1	strains					467:473	15 PEDV representative strains	444:473	15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	444:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	0	79	theme	strains	91:97	arg1	analysis					18:25	Genetic evolution analysis	0:25	Genetic evolution analysis	0:25	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	0	79	theme	strains	91:97	arg1	assessment					45:54	pathogenicity assessment	31:54	pathogenicity assessment	31:54	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	5	80	theme	96.3-99.8	1029:1037	arg1	%					1038:1038	%	1038:1038	%	1038:1038	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	4	81	from	mutations	814:822	arg1	proteins					835:842	their S proteins	827:842	their S proteins	827:842	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	7	82	theme	oral	1460:1463	arg1	routes					1493:1498	oral and intramuscular infection routes	1460:1498	oral and intramuscular infection routes	1460:1498	We evaluated the pathogenicity of the PEDV strain FJzz1 in piglets through oral and intramuscular infection routes.
30677534	4	83	contain	had	791:793	arg2	mutations					814:822	103-120 amino acid mutations	795:822	103-120 amino acid mutations	795:822	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	4	83	contain	had	791:793	arg1	strains					783:789	these strains	777:789	these strains	777:789	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	6	84	theme	glycosylation	1268:1280	arg1	S1-NTD					1291:1296	S1-NTD	1291:1296	S1-NTD	1291:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	84	theme	glycosylation	1268:1280	arg1	sites					1282:1286	asparagine (N)-linked glycosylation sites	1246:1286	asparagine (N)-linked glycosylation sites of S1-NTD	1246:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	5	85	theme	amino	1040:1044	arg1	homology					1051:1058	96.3-99.8% amino acid homology	1029:1058	96.3-99.8% amino acid homology in the S protein	1029:1075	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	4	86	theme	terminal	873:880	arg1	S1					892:893	S1	892:893	S1 (S1-NTD)	892:902	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	4	86	theme	terminal	873:880	arg1	domain					882:887	the N terminal domain	867:887	the N terminal domain of S1 (S1-NTD)	867:902	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	10	87	theme	PEDV	2050:2053	arg1	isolates					2055:2062	the epidemic PEDV isolates	2037:2062	the epidemic PEDV isolates	2037:2062	This study shows the necessity of monitoring the molecular epidemiology and the etiological characteristics of the epidemic PEDV isolates, which may help better control the PED outbreaks.
30677534	5	88	theme	%	1003:1003	arg1	homology					1016:1023	96.9-99.7% nucleotide homology	994:1023	96.9-99.7% nucleotide homology	994:1023	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	2	89	theme	strains	467:473	arg1	evolution					431:439	the genetic evolution	419:439	the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	419:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	0	90	theme	evolution	8:16	arg1	analysis					18:25	Genetic evolution analysis	0:25	Genetic evolution analysis	0:25	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	1	91	theme	severe	333:338	arg1	impacts					349:355	severe economic impacts	333:355	severe economic impacts to the pork industry	333:376	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	2	92	theme	fecal	499:503	arg1	samples					505:511	fecal samples	499:511	fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	499:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	1	93	theme	virus	268:272	arg1	variants					281:288	the highly virulent porcine epidemic diarrhea virus (PEDV) variants	222:288	the highly virulent porcine epidemic diarrhea virus (PEDV) variants	222:288	In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry.
30677534	10	94	theme	epidemic	2041:2048	arg1	isolates					2055:2062	the epidemic PEDV isolates	2037:2062	the epidemic PEDV isolates	2037:2062	This study shows the necessity of monitoring the molecular epidemiology and the etiological characteristics of the epidemic PEDV isolates, which may help better control the PED outbreaks.
30677534	5	95	theme	common	922:927	arg1	mutations					929:937	37 common mutations	919:937	37 common mutations in all these 15 strains	919:961	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	6	96	theme	strains	1376:1382	arg1	pathogenicity					1340:1352	the altered pathogenicity	1328:1352	the altered pathogenicity of these variant PEDV strains	1328:1382	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	2	97	theme	genetic	423:429	arg1	evolution					431:439	the genetic evolution	419:439	the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017	419:576	In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017.
30677534	0	98	theme	porcine	59:65	arg1	strains					91:97	porcine epidemic diarrhea virus strains	59:97	porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017	59:143	Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.
30677534	6	99	from	changes	1202:1208	arg1	S1-NTD					1291:1296	S1-NTD	1291:1296	S1-NTD	1291:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	99	from	changes	1202:1208	arg1	structure					1232:1240	conformational structure	1217:1240	conformational structure	1217:1240	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	6	99	from	changes	1202:1208	arg1	sites					1282:1286	asparagine (N)-linked glycosylation sites	1246:1286	asparagine (N)-linked glycosylation sites of S1-NTD	1246:1296	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30677534	7	100	theme	strain	1428:1433	arg1	FJzz1					1435:1439	the PEDV strain FJzz1	1419:1439	the PEDV strain FJzz1	1419:1439	We evaluated the pathogenicity of the PEDV strain FJzz1 in piglets through oral and intramuscular infection routes.
30677534	5	101	theme	nucleotide	1005:1014	arg1	homology					1016:1023	96.9-99.7% nucleotide homology	994:1023	96.9-99.7% nucleotide homology	994:1023	We also found 37 common mutations in all these 15 strains, although these strains shared 96.9-99.7% nucleotide homology and 96.3-99.8% amino acid homology in the S protein compared with the other original pandemic strains.
30677534	3	102	theme	PEDV	631:634	arg1	isolates					636:643	all the 15 PEDV isolates	620:643	all the 15 PEDV isolates	620:643	The phylogenetic analysis indicated that all the 15 PEDV isolates clustered into G2 genotype associated with the current circulating strains.
30677534	8	103	theme	clinical	1580:1587	arg1	signs					1589:1593	typical clinical signs	1572:1593	typical clinical signs	1572:1593	Compared with oral infection, intramuscular infection could also cause typical clinical signs but with a slightly delayed onset, confirming that the variant PEDV isolate FJzz1 was highly pathogenic to suckling piglets.
30677534	3	104	theme	G2	660:661	arg1	genotype					663:670	G2 genotype	660:670	G2 genotype associated with the current circulating strains	660:718	The phylogenetic analysis indicated that all the 15 PEDV isolates clustered into G2 genotype associated with the current circulating strains.
30677534	4	105	theme	strain	763:768	arg1	genome					739:744	the genome	735:744	the genome of the prototype strain CV777	735:774	Compared with the genome of the prototype strain CV777, these strains had 103-120 amino acid mutations in their S proteins, most of which were in the N terminal domain of S1 (S1-NTD).
30677534	6	106	theme	PEDV	1371:1374	arg1	strains					1376:1382	these variant PEDV strains	1357:1382	these variant PEDV strains	1357:1382	Computational analysis showed that these mutations may lead to remarkable changes in the conformational structure and asparagine (N)-linked glycosylation sites of S1-NTD, which may be associated with the altered pathogenicity of these variant PEDV strains.
30487389	0	0	theme	moojeni	71:77	arg1	Venom					85:89	Bothrops moojeni Snake Venom	62:89	Bothrops moojeni Snake Venom	62:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	1	1	theme	drugs	303:307	arg1	development					272:282	the development	268:282	the development of new therapeutic drugs	268:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	3	2	attach	isolated	432:439	arg2	toxin					422:426	The toxin	418:426	The toxin	418:426	The toxin was isolated from the crude venom using a two-step chromatographic procedure.
30487389	3	2	attach	isolated	432:439	arg1	venom					456:460	the crude venom	446:460	the crude venom using a two-step chromatographic procedure	446:503	The toxin was isolated from the crude venom using a two-step chromatographic procedure.
30487389	1	3	theme	cascade	215:221	arg1	parts					184:188	various parts	176:188	various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs	176:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	0	4	theme	Bothrops	62:69	arg1	Venom					85:89	Bothrops moojeni Snake Venom	62:89	Bothrops moojeni Snake Venom	62:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	0	5	from	Insights	4:11	arg1	Protease					48:55	a Thrombin-Like Serine Protease	25:55	a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom	25:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	0	5	from	Insights	4:11	arg1	Moojase					16:22	Moojase	16:22	Moojase	16:22	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	8	6	theme	factor	1387:1392	arg1	XIIa					1394:1397	factor XIIa	1387:1397	factor XIIa	1387:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	6	theme	factor	1387:1392	arg1	substrates					1327:1336	substrates	1327:1336	substrates for thrombin	1327:1349	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	7	theme	platelets	1270:1278	arg1	activity					1315:1322	significant amidolytic activity	1292:1322	significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa	1292:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	7	theme	platelets	1270:1278	arg1	aggregation					1248:1258	the aggregation	1244:1258	the aggregation of washed platelets	1244:1278	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	4	8	theme	N-linked	537:544	arg1	character					593:601	acidic character	586:601	acidic character (pI 5.80⁻6.88)	586:616	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	8	theme	N-linked	537:544	arg1	glycans					546:552	N-linked glycans	537:552	N-linked glycans	537:552	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	8	theme	N-linked	537:544	arg1	mass					565:568	molecular mass	555:568	molecular mass of 30.3 kDa	555:580	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	10	9	from	prototypes	1667:1676	arg1	development					1685:1695	the development	1681:1695	the development of new drugs	1681:1708	Thus, studies such as this for Moojase should increase knowledge on SVSPs, allowing their bioprospection as valuable prototypes in the development of new drugs, or as biotechnological tools.
30487389	10	10	theme	drugs	1704:1708	arg1	development					1685:1695	the development	1681:1695	the development of new drugs	1681:1708	Thus, studies such as this for Moojase should increase knowledge on SVSPs, allowing their bioprospection as valuable prototypes in the development of new drugs, or as biotechnological tools.
30487389	9	11	theme	esterase	1442:1449	arg1	activity					1451:1458	the esterase activity	1438:1458	the esterase activity of Moojase	1438:1469	Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures.
30487389	7	12	theme	chains	879:884	arg1	proteolysis					857:867	the proteolysis	853:867	the proteolysis of the Aα chains of human fibrinogen	853:904	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	4	13	theme	molecular	555:563	arg1	glycans					546:552	N-linked glycans	537:552	N-linked glycans	537:552	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	13	theme	molecular	555:563	arg1	mass					565:568	molecular mass	555:568	molecular mass of 30.3 kDa	555:580	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	0	14	theme	Snake	79:83	arg1	Venom					85:89	Bothrops moojeni Snake Venom	62:89	Bothrops moojeni Snake Venom	62:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	9	15	theme	high	1493:1496	arg1	stability					1498:1506	its very high stability	1484:1506	its very high stability	1484:1506	Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures.
30487389	10	16	theme	valuable	1658:1665	arg1	prototypes					1667:1676	valuable prototypes	1658:1676	valuable prototypes in the development of new drugs	1658:1708	Thus, studies such as this for Moojase should increase knowledge on SVSPs, allowing their bioprospection as valuable prototypes in the development of new drugs, or as biotechnological tools.
30487389	4	17	with	glycoprotein	519:530	arg1	character					593:601	acidic character	586:601	acidic character (pI 5.80⁻6.88)	586:616	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	17	with	glycoprotein	519:530	arg1	glycans					546:552	N-linked glycans	537:552	N-linked glycans	537:552	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	17	with	glycoprotein	519:530	arg1	mass					565:568	molecular mass	555:568	molecular mass of 30.3 kDa	555:580	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	5	18	theme	Batroxobin	676:685	arg1	it					656:657	it	656:657	it	656:657	Sequencing of Moojase indicated that it is an isoform of Batroxobin.
30487389	5	18	theme	Batroxobin	676:685	arg1	isoform					665:671	an isoform	662:671	an isoform of Batroxobin	662:685	Sequencing of Moojase indicated that it is an isoform of Batroxobin.
30487389	8	19	theme	clots	1217:1221	arg1	fibrinolysis					1194:1205	the fibrinolysis	1190:1205	the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa	1190:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	6	20	theme	fibrinogen	738:747	arg1	solutions					749:757	fibrinogen solutions	738:757	fibrinogen solutions	738:757	Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties.
30487389	3	21	theme	chromatographic	479:493	arg1	procedure					495:503	a two-step chromatographic procedure	468:503	a two-step chromatographic procedure	468:503	The toxin was isolated from the crude venom using a two-step chromatographic procedure.
30487389	8	22	from	activity	1315:1322	arg1	XIIa					1394:1397	factor XIIa	1387:1397	factor XIIa	1387:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	22	from	activity	1315:1322	arg1	Xia					1378:1380	factor Xia	1371:1380	factor Xia	1371:1380	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	22	from	activity	1315:1322	arg1	kallikrein					1359:1368	plasma kallikrein	1352:1368	plasma kallikrein	1352:1368	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	22	from	activity	1315:1322	arg1	substrates					1327:1336	substrates	1327:1336	substrates for thrombin	1327:1349	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	9	23	theme	Moojase	1463:1469	arg1	analyses					1425:1432	thermofluor analyses	1413:1432	thermofluor analyses	1413:1432	Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures.
30487389	9	23	theme	Moojase	1463:1469	arg1	activity					1451:1458	the esterase activity	1438:1458	the esterase activity of Moojase	1438:1469	Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures.
30487389	8	24	theme	RP-HPLC	1077:1083	arg1	analysis					1085:1092	RP-HPLC analysis	1077:1092	RP-HPLC analysis of its fibrinogenolysis	1077:1116	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	25	theme	washed	1263:1268	arg1	platelets					1270:1278	washed platelets	1263:1278	washed platelets	1263:1278	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	7	26	theme	human	889:893	arg1	fibrinogen					895:904	human fibrinogen	889:904	human fibrinogen	889:904	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	2	27	theme	snake	405:409	arg1	venom					411:415	Bothrops moojeni snake venom	388:415	Bothrops moojeni snake venom	388:415	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	4	28	theme	pI	604:605	arg1	character					593:601	acidic character	586:601	acidic character (pI 5.80⁻6.88)	586:616	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	28	theme	pI	604:605	arg1	5.80⁻6.88					607:615	pI 5.80⁻6.88	604:615	pI 5.80⁻6.88	604:615	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	7	29	theme	fibrinogen	895:904	arg1	chains					879:884	the Aα chains	872:884	the Aα chains of human fibrinogen	872:904	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	0	30	theme	New	0:2	arg1	Insights					4:11	New Insights	0:11	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom	0:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	6	31	theme	dose-dependent	764:777	arg1	manner					779:784	a dose-dependent manner	762:784	a dose-dependent manner	762:784	Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties.
30487389	6	32	theme	platelet-poor	713:725	arg1	plasma					727:732	clot platelet-poor plasma	708:732	clot platelet-poor plasma	708:732	Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties.
30487389	8	33	theme	plasma	1352:1357	arg1	kallikrein					1359:1368	plasma kallikrein	1352:1368	plasma kallikrein	1352:1368	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	33	theme	plasma	1352:1357	arg1	substrates					1327:1336	substrates	1327:1336	substrates for thrombin	1327:1349	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	2	34	theme	moojeni	397:403	arg1	venom					411:415	Bothrops moojeni snake venom	388:415	Bothrops moojeni snake venom	388:415	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	1	35	theme	interesting	241:251	arg1	candidates					253:262	interesting candidates	241:262	interesting candidates for the development of new therapeutic drugs	241:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	6	36	theme	clot	708:711	arg1	plasma					727:732	clot platelet-poor plasma	708:732	clot platelet-poor plasma	708:732	Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties.
30487389	8	37	theme	main	1132:1135	arg1	generation					1137:1146	the main generation	1128:1146	the main generation of fibrinopeptide	1128:1164	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	38	dep	induced	1182:1188	arg1	confirmed					1118:1126	confirmed	1118:1126	confirmed the main generation of fibrinopeptide	1118:1164	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	4	39	theme	acidic	586:591	arg1	character					593:601	acidic character	586:601	acidic character (pI 5.80⁻6.88)	586:616	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	39	theme	acidic	586:591	arg1	5.80⁻6.88					607:615	pI 5.80⁻6.88	604:615	pI 5.80⁻6.88	604:615	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	39	theme	acidic	586:591	arg1	glycans					546:552	N-linked glycans	537:552	N-linked glycans	537:552	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	2	40	theme	Bothrops	388:395	arg1	venom					411:415	Bothrops moojeni snake venom	388:415	Bothrops moojeni snake venom	388:415	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	7	41	theme	chains	945:950	arg1	degradation					923:933	the degradation	919:933	the degradation of the Bβ chains	919:950	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	1	42	theme	Snake	92:96	arg1	proteases					111:119	Snake venom serine proteases	92:119	Snake venom serine proteases (SVSPs)	92:127	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	42	theme	Snake	92:96	arg1	SVSPs					122:126	SVSPs	122:126	SVSPs	122:126	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	42	theme	Snake	92:96	arg1	enzymes					133:139	enzymes	133:139	enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs	133:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	10	43	from	knowledge	1605:1613	arg1	SVSPs					1618:1622	SVSPs	1618:1622	SVSPs	1618:1622	Thus, studies such as this for Moojase should increase knowledge on SVSPs, allowing their bioprospection as valuable prototypes in the development of new drugs, or as biotechnological tools.
30487389	6	44	from	manner	779:784	arg1	able					700:703	able	700:703	able	700:703	Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties.
30487389	3	45	theme	crude	450:454	arg1	venom					456:460	the crude venom	446:460	the crude venom using a two-step chromatographic procedure	446:503	The toxin was isolated from the crude venom using a two-step chromatographic procedure.
30487389	10	46	theme	new	1700:1702	arg1	drugs					1704:1708	new drugs	1700:1708	new drugs	1700:1708	Thus, studies such as this for Moojase should increase knowledge on SVSPs, allowing their bioprospection as valuable prototypes in the development of new drugs, or as biotechnological tools.
30487389	1	47	theme	various	176:182	arg1	parts					184:188	various parts	176:188	various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs	176:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	8	48	theme	amidolytic	1304:1313	arg1	activity					1315:1322	significant amidolytic activity	1292:1322	significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa	1292:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	49	from	aggregation	1248:1258	arg1	XIIa					1394:1397	factor XIIa	1387:1397	factor XIIa	1387:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	49	from	aggregation	1248:1258	arg1	Xia					1378:1380	factor Xia	1371:1380	factor Xia	1371:1380	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	49	from	aggregation	1248:1258	arg1	kallikrein					1359:1368	plasma kallikrein	1352:1368	plasma kallikrein	1352:1368	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	49	from	aggregation	1248:1258	arg1	substrates					1327:1336	substrates	1327:1336	substrates for thrombin	1327:1349	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	2	50	theme	coagulant	366:374	arg1	enzyme					376:381	a potent coagulant enzyme	357:381	a potent coagulant enzyme from Bothrops moojeni snake venom	357:415	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	2	50	theme	coagulant	366:374	arg1	Moojase					348:354	Moojase	348:354	Moojase	348:354	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	8	51	theme	factor	1371:1376	arg1	substrates					1327:1336	substrates	1327:1336	substrates for thrombin	1327:1349	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	8	51	theme	factor	1371:1376	arg1	Xia					1378:1380	factor Xia	1371:1380	factor Xia	1371:1380	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	4	52	theme	kDa	578:580	arg1	character					593:601	acidic character	586:601	acidic character (pI 5.80⁻6.88)	586:616	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	52	theme	kDa	578:580	arg1	5.80⁻6.88					607:615	pI 5.80⁻6.88	604:615	pI 5.80⁻6.88	604:615	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	52	theme	kDa	578:580	arg1	glycans					546:552	N-linked glycans	537:552	N-linked glycans	537:552	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	52	theme	kDa	578:580	arg1	mass					565:568	molecular mass	555:568	molecular mass of 30.3 kDa	555:580	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	7	53	theme	extended	958:965	arg1	periods					967:973	extended periods	958:973	extended periods of incubation	958:987	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	2	54	theme	potent	359:364	arg1	enzyme					376:381	a potent coagulant enzyme	357:381	a potent coagulant enzyme from Bothrops moojeni snake venom	357:415	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	2	54	theme	potent	359:364	arg1	Moojase					348:354	Moojase	348:354	Moojase	348:354	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	0	55	theme	Serine	41:46	arg1	Protease					48:55	a Thrombin-Like Serine Protease	25:55	a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom	25:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	0	55	theme	Serine	41:46	arg1	Moojase					16:22	Moojase	16:22	Moojase	16:22	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	6	56	theme	thrombin-like	798:810	arg1	properties					812:821	thrombin-like properties	798:821	thrombin-like properties	798:821	Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties.
30487389	9	57	theme	different	1511:1519	arg1	buffers					1524:1530	different pH buffers	1511:1530	different pH buffers	1511:1530	Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures.
30487389	1	58	theme	venom	98:102	arg1	proteases					111:119	Snake venom serine proteases	92:119	Snake venom serine proteases (SVSPs)	92:127	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	58	theme	venom	98:102	arg1	SVSPs					122:126	SVSPs	122:126	SVSPs	122:126	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	58	theme	venom	98:102	arg1	enzymes					133:139	enzymes	133:139	enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs	133:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	0	59	theme	Thrombin-Like	27:39	arg1	Protease					48:55	a Thrombin-Like Serine Protease	25:55	a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom	25:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	0	59	theme	Thrombin-Like	27:39	arg1	Moojase					16:22	Moojase	16:22	Moojase	16:22	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	9	60	theme	pH	1521:1522	arg1	buffers					1524:1530	different pH buffers	1511:1530	different pH buffers	1511:1530	Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures.
30487389	4	61	gly	glycoprotein	519:530	arg1	Moojase					506:512	Moojase	506:512	Moojase	506:512	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	61	gly	glycoprotein	519:530	arg1	glycoprotein					519:530	a glycoprotein	517:530	a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88)	517:616	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	1	62	theme	serine	104:109	arg1	proteases					111:119	Snake venom serine proteases	92:119	Snake venom serine proteases (SVSPs)	92:127	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	62	theme	serine	104:109	arg1	SVSPs					122:126	SVSPs	122:126	SVSPs	122:126	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	62	theme	serine	104:109	arg1	enzymes					133:139	enzymes	133:139	enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs	133:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	63	theme	new	287:289	arg1	drugs					303:307	new therapeutic drugs	287:307	new therapeutic drugs	287:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	5	64	theme	Moojase	633:639	arg1	Sequencing					619:628	Sequencing	619:628	Sequencing of Moojase	619:639	Sequencing of Moojase indicated that it is an isoform of Batroxobin.
30487389	8	65	theme	significant	1292:1302	arg1	activity					1315:1322	significant amidolytic activity	1292:1322	significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa	1292:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	7	66	theme	Aα	876:877	arg1	chains					879:884	the Aα chains	872:884	the Aα chains of human fibrinogen	872:904	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	7	67	theme	incubation	978:987	arg1	periods					967:973	extended periods	958:973	extended periods of incubation	958:987	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	0	68	from	Venom	85:89	arg1	Protease					48:55	a Thrombin-Like Serine Protease	25:55	a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom	25:89	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	0	68	from	Venom	85:89	arg1	Moojase					16:22	Moojase	16:22	Moojase	16:22	New Insights on Moojase, a Thrombin-Like Serine Protease from Bothrops moojeni Snake Venom.
30487389	6	69	from	able	700:703	arg1	manner					779:784	a dose-dependent manner	762:784	a dose-dependent manner	762:784	Moojase was able to clot platelet-poor plasma and fibrinogen solutions in a dose-dependent manner, indicating thrombin-like properties.
30487389	10	70	theme	biotechnological	1717:1732	arg1	tools					1734:1738	biotechnological tools	1717:1738	biotechnological tools	1717:1738	Thus, studies such as this for Moojase should increase knowledge on SVSPs, allowing their bioprospection as valuable prototypes in the development of new drugs, or as biotechnological tools.
30487389	2	71	from	venom	411:415	arg1	enzyme					376:381	a potent coagulant enzyme	357:381	a potent coagulant enzyme from Bothrops moojeni snake venom	357:415	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	2	71	from	venom	411:415	arg1	Moojase					348:354	Moojase	348:354	Moojase	348:354	Herein, we isolated and characterized Moojase, a potent coagulant enzyme from Bothrops moojeni snake venom.
30487389	4	72	link	N-linked	537:544	arg1	character					593:601	acidic character	586:601	acidic character (pI 5.80⁻6.88)	586:616	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	72	link	N-linked	537:544	arg1	glycans					546:552	N-linked glycans	537:552	N-linked glycans	537:552	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	4	72	link	N-linked	537:544	arg1	mass					565:568	molecular mass	555:568	molecular mass of 30.3 kDa	555:580	Moojase is a glycoprotein with N-linked glycans, molecular mass of 30.3 kDa and acidic character (pI 5.80⁻6.88).
30487389	8	73	dep	clots	1217:1221	arg1	formed					1223:1228	formed	1223:1228	formed in vitro	1223:1237	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	7	74	theme	Bβ	942:943	arg1	chains					945:950	the Bβ chains	938:950	the Bβ chains	938:950	Moojase also rapidly induced the proteolysis of the Aα chains of human fibrinogen, followed by the degradation of the Bβ chains after extended periods of incubation, and these effects were inhibited by PMSF, SDS and DTT, but not by benzamidine or EDTA.
30487389	9	75	theme	thermofluor	1413:1423	arg1	analyses					1425:1432	thermofluor analyses	1413:1432	thermofluor analyses	1413:1432	Furthermore, thermofluor analyses and the esterase activity of Moojase demonstrated its very high stability at different pH buffers and temperatures.
30487389	8	76	theme	fibrinopeptide	1151:1164	arg1	generation					1137:1146	the main generation	1128:1146	the main generation of fibrinopeptide	1128:1164	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	1	77	theme	blood	197:201	arg1	cascade					215:221	the blood coagulation cascade	193:221	the blood coagulation cascade	193:221	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	1	78	theme	therapeutic	291:301	arg1	drugs					303:307	new therapeutic drugs	287:307	new therapeutic drugs	287:307	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
30487389	8	79	theme	fibrinogenolysis	1101:1116	arg1	analysis					1085:1092	RP-HPLC analysis	1077:1092	RP-HPLC analysis of its fibrinogenolysis	1077:1116	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	3	80	theme	two-step	470:477	arg1	procedure					495:503	a two-step chromatographic procedure	468:503	a two-step chromatographic procedure	468:503	The toxin was isolated from the crude venom using a two-step chromatographic procedure.
30487389	8	81	theme	fibrin	1210:1215	arg1	clots					1217:1221	fibrin clots	1210:1221	fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa	1210:1397	RP-HPLC analysis of its fibrinogenolysis confirmed the main generation of fibrinopeptide A. Moojase also induced the fibrinolysis of fibrin clots formed in vitro, and the aggregation of washed platelets, as well as significant amidolytic activity on substrates for thrombin, plasma kallikrein, factor Xia, and factor XIIa.
30487389	1	82	theme	coagulation	203:213	arg1	cascade					215:221	the blood coagulation cascade	193:221	the blood coagulation cascade	193:221	Snake venom serine proteases (SVSPs) are enzymes that are capable of interfering in various parts of the blood coagulation cascade, which makes them interesting candidates for the development of new therapeutic drugs.
29090410	0	0	theme	virus	92:96	arg1	analysis					8:15	Genomic analysis	0:15	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.	0:106	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	2	1	theme	full-length	459:469	arg1	sequence					478:485	the full-length genome sequence	455:485	the full-length genome sequence	455:485	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	5	2	contain	contained	848:856	arg2	mutations					879:887	extensive amino acid mutations	858:887	extensive amino acid mutations in GP5	858:894	Furthermore, HNhx strain contained extensive amino acid mutations in GP5.
29090410	5	2	contain	contained	848:856	arg1	strain					841:846	HNhx strain	836:846	HNhx strain	836:846	Furthermore, HNhx strain contained extensive amino acid mutations in GP5.
29090410	1	3	theme	syndrome	167:174	arg1	PRRSVs					185:190	PRRSVs	185:190	PRRSVs	185:190	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	1	3	theme	syndrome	167:174	arg1	viruses					176:182	NADC30-like porcine reproductive and respiratory syndrome viruses	118:182	NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs)	118:191	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	6	4	dep	resulted	954:961	arg1	lost					976:979	lost	976:979	lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35	976:1072	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	6	5	theme	S36G	938:941	arg1	variations					943:952	S36G variations	938:952	S36G variations	938:952	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	0	6	theme	syndrome	83:90	arg1	virus					92:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	0	7	from	analysis	8:15	arg1	china					101:105	china	101:105	china	101:105	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	5	8	theme	amino	868:872	arg1	mutations					879:887	extensive amino acid mutations	858:887	extensive amino acid mutations in GP5	858:894	Furthermore, HNhx strain contained extensive amino acid mutations in GP5.
29090410	5	9	theme	acid	874:877	arg1	mutations					879:887	extensive amino acid mutations	858:887	extensive amino acid mutations in GP5	858:894	Furthermore, HNhx strain contained extensive amino acid mutations in GP5.
29090410	8	10	from	epidemiology	1362:1373	arg1	China					1387:1391	China	1387:1391	China	1387:1391	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	8	11	from	evolution	1348:1356	arg1	China					1387:1391	China	1387:1391	China	1387:1391	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	6	12	theme	amino	1030:1034	arg1	positions					1041:1049	amino acid positions	1030:1049	amino acid positions 30, 32, 33, 34, and 35	1030:1072	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	3	13	theme	relative	682:689	arg1	deletion					673:680	the unique discontinuous 131-amino acid deletion	633:680	the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain	633:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	1	14	from	2008	289:292	arg1	States					268:273	the United States	257:273	the United States of America in 2008	257:292	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	5	15	theme	extensive	858:866	arg1	mutations					879:887	extensive amino acid mutations	858:887	extensive amino acid mutations in GP5	858:894	Furthermore, HNhx strain contained extensive amino acid mutations in GP5.
29090410	3	16	theme	nonstructural	706:718	arg1	Nsp2					731:734	Nsp2	731:734	Nsp2	731:734	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	3	16	theme	nonstructural	706:718	arg1	protein					720:726	the nonstructural protein 2	702:728	the nonstructural protein 2 (Nsp2) of the VR2332 strain	702:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	3	17	theme	HNhx	540:543	arg1	strain					545:550	HNhx strain	540:550	HNhx strain	540:550	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	1	18	theme	United	261:266	arg1	States					268:273	the United States	257:273	the United States of America in 2008	257:292	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	1	19	from	prevalent	307:315	arg1	China					320:324	China	320:324	China	320:324	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	8	20	theme	PRRSV	1378:1382	arg1	epidemiology					1362:1373	epidemiology	1362:1373	epidemiology	1362:1373	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	8	20	theme	PRRSV	1378:1382	arg1	evolution					1348:1356	evolution	1348:1356	evolution	1348:1356	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	5	21	theme	HNhx	836:839	arg1	strain					841:846	HNhx strain	836:846	HNhx strain	836:846	Furthermore, HNhx strain contained extensive amino acid mutations in GP5.
29090410	8	22	dep	evolution	1348:1356	arg1	the					1344:1346	the	1344:1346	the	1344:1346	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	0	23	theme	NADC30-like	34:44	arg1	virus					92:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	2	24	theme	alveolar	410:417	arg1	macrophages					419:429	porcine alveolar macrophages	402:429	porcine alveolar macrophages from Henan province	402:449	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	6	25	theme	glycosylation	1007:1019	arg1	sites					1021:1025	the putative N-linked glycosylation sites	985:1025	all the putative N-linked glycosylation sites	981:1025	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	2	26	from	province	442:449	arg1	macrophages					419:429	porcine alveolar macrophages	402:429	porcine alveolar macrophages from Henan province	402:449	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	1	27	from	States	268:273	arg1	2008					289:292	2008	289:292	2008	289:292	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	6	28	theme	N-linked	998:1005	arg1	sites					1021:1025	the putative N-linked glycosylation sites	985:1025	all the putative N-linked glycosylation sites	981:1025	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	2	29	theme	PRRSV	349:353	arg1	strain					355:360	a novel variant PRRSV strain	333:360	a novel variant PRRSV strain named HNhx	333:371	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	0	30	theme	Genomic	0:6	arg1	analysis					8:15	Genomic analysis	0:15	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.	0:106	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	5	31	from	mutations	879:887	arg1	GP5					892:894	GP5	892:894	GP5	892:894	Furthermore, HNhx strain contained extensive amino acid mutations in GP5.
29090410	2	32	theme	variant	341:347	arg1	strain					355:360	a novel variant PRRSV strain	333:360	a novel variant PRRSV strain named HNhx	333:371	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	2	33	theme	porcine	402:408	arg1	macrophages					419:429	porcine alveolar macrophages	402:429	porcine alveolar macrophages from Henan province	402:449	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	4	34	theme	%	788:788	arg1	similarity					801:810	92.9% nucleotide similarity	784:810	92.9% nucleotide similarity to NADC30	784:820	Genetically, HNhx shared 92.9% nucleotide similarity to NADC30.
29090410	7	35	theme	nt	1270:1271	arg1	Nsp9					1264:1267	Nsp9	1264:1267	Nsp9 (nt 7911)	1264:1277	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	7	35	theme	nt	1270:1271	arg1	7911					1273:1276	nt 7911	1270:1276	nt 7911	1270:1276	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	4	36	theme	92.9	784:787	arg1	%					788:788	%	788:788	%	788:788	Genetically, HNhx shared 92.9% nucleotide similarity to NADC30.
29090410	7	37	theme	vaccine	1207:1213	arg1	strain					1215:1220	the highly pathogenic PRRSV vaccine strain	1179:1220	the highly pathogenic PRRSV vaccine strain	1179:1220	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	3	38	theme	Phylogenetic	503:514	arg1	analysis					516:523	Phylogenetic analysis	503:523	Phylogenetic analysis	503:523	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	1	39	theme	America	278:284	arg1	States					268:273	the United States	257:273	the United States of America in 2008	257:292	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	8	40	theme	HNhx	1305:1308	arg1	helpful					1318:1324	helpful	1318:1324	helpful	1318:1324	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	8	40	theme	HNhx	1305:1308	arg1	data					1297:1300	The novel genome data	1280:1300	The novel genome data of HNhx	1280:1308	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	1	41	from	China	320:324	arg1	prevalent					307:315	prevalent	307:315	prevalent	307:315	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	7	42	theme	PRRSV	1201:1205	arg1	strain					1215:1220	the highly pathogenic PRRSV vaccine strain	1179:1220	the highly pathogenic PRRSV vaccine strain	1179:1220	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	7	43	theme	Recombination	1075:1087	arg1	analysis					1089:1096	Recombination analysis	1075:1096	Recombination analysis	1075:1096	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	3	44	theme	PRRSV	588:592	arg1	subgroup					594:601	the NADC30-like PRRSV subgroup	572:601	the NADC30-like PRRSV subgroup	572:601	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	6	45	theme	putative	989:996	arg1	sites					1021:1025	the putative N-linked glycosylation sites	985:1025	all the putative N-linked glycosylation sites	981:1025	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	7	46	theme	pathogenic	1190:1199	arg1	strain					1215:1220	the highly pathogenic PRRSV vaccine strain	1179:1220	the highly pathogenic PRRSV vaccine strain	1179:1220	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	0	47	theme	recombinant	22:32	arg1	virus					92:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	3	48	theme	VR2332	744:749	arg1	strain					751:756	the VR2332 strain	740:756	the VR2332 strain	740:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	3	49	contain	had	629:631	arg2	deletion					673:680	the unique discontinuous 131-amino acid deletion	633:680	the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain	633:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	3	49	contain	had	629:631	arg1	strains					621:627	all the strains	613:627	all the strains	613:627	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	0	50	theme	reproductive	54:65	arg1	virus					92:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	3	51	theme	strain	751:756	arg1	Nsp2					731:734	Nsp2	731:734	Nsp2	731:734	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	3	51	theme	strain	751:756	arg1	protein					720:726	the nonstructural protein 2	702:728	the nonstructural protein 2 (Nsp2) of the VR2332 strain	702:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	6	52	gly	glycosylation	1007:1019	arg2	sites					1021:1025	the putative N-linked glycosylation sites	985:1025	all the putative N-linked glycosylation sites	981:1025	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	4	53	theme	nucleotide	790:799	arg1	similarity					801:810	92.9% nucleotide similarity	784:810	92.9% nucleotide similarity to NADC30	784:820	Genetically, HNhx shared 92.9% nucleotide similarity to NADC30.
29090410	6	54	theme	acid	1036:1039	arg1	positions					1041:1049	amino acid positions	1030:1049	amino acid positions 30, 32, 33, 34, and 35	1030:1072	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	0	55	theme	porcine	46:52	arg1	virus					92:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	3	56	theme	131-amino	658:666	arg1	deletion					673:680	the unique discontinuous 131-amino acid deletion	633:680	the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain	633:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	3	57	theme	NADC30-like	576:586	arg1	subgroup					594:601	the NADC30-like PRRSV subgroup	572:601	the NADC30-like PRRSV subgroup	572:601	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	1	58	theme	NADC30-like	118:128	arg1	PRRSVs					185:190	PRRSVs	185:190	PRRSVs	185:190	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	1	58	theme	NADC30-like	118:128	arg1	viruses					176:182	NADC30-like porcine reproductive and respiratory syndrome viruses	118:182	NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs)	118:191	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	7	59	theme	NADC30	1161:1166	arg1	strain					1168:1173	the NADC30 strain	1157:1173	the NADC30 strain	1157:1173	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	3	60	theme	acid	668:671	arg1	deletion					673:680	the unique discontinuous 131-amino acid deletion	633:680	the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain	633:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	8	61	theme	novel	1284:1288	arg1	helpful					1318:1324	helpful	1318:1324	helpful	1318:1324	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	8	61	theme	novel	1284:1288	arg1	data					1297:1300	The novel genome data	1280:1300	The novel genome data of HNhx	1280:1308	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	3	62	theme	unique	637:642	arg1	deletion					673:680	the unique discontinuous 131-amino acid deletion	633:680	the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain	633:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	1	63	theme	reproductive	138:149	arg1	PRRSVs					185:190	PRRSVs	185:190	PRRSVs	185:190	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	1	63	theme	reproductive	138:149	arg1	viruses					176:182	NADC30-like porcine reproductive and respiratory syndrome viruses	118:182	NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs)	118:191	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	0	64	theme	respiratory	71:81	arg1	virus					92:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	a recombinant NADC30-like porcine reproductive and respiratory syndrome virus	20:96	Genomic analysis of a recombinant NADC30-like porcine reproductive and respiratory syndrome virus in china.
29090410	3	65	theme	discontinuous	644:656	arg1	deletion					673:680	the unique discontinuous 131-amino acid deletion	633:680	the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain	633:756	Phylogenetic analysis indicated that HNhx strain was classified into the NADC30-like PRRSV subgroup, in which all the strains had the unique discontinuous 131-amino acid deletion relative to that of the nonstructural protein 2 (Nsp2) of the VR2332 strain.
29090410	2	66	theme	novel	335:339	arg1	strain					355:360	a novel variant PRRSV strain	333:360	a novel variant PRRSV strain named HNhx	333:371	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	1	67	theme	NADC30	231:236	arg1	strain					238:243	the NADC30 strain	227:243	the NADC30 strain isolated in the United States of America in 2008	227:292	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	2	68	theme	genome	471:476	arg1	sequence					478:485	the full-length genome sequence	455:485	the full-length genome sequence	455:485	Here, a novel variant PRRSV strain named HNhx was successfully isolated on porcine alveolar macrophages from Henan province and the full-length genome sequence was determined.
29090410	6	69	link	N-linked	998:1005	arg1	sites					1021:1025	the putative N-linked glycosylation sites	985:1025	all the putative N-linked glycosylation sites	981:1025	In particular, the S32H, N33D, D34N, and S36G variations resulted in that HNhx lost all the putative N-linked glycosylation sites at amino acid positions 30, 32, 33, 34, and 35.
29090410	8	70	theme	genome	1290:1295	arg1	helpful					1318:1324	helpful	1318:1324	helpful	1318:1324	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	8	70	theme	genome	1290:1295	arg1	data					1297:1300	The novel genome data	1280:1300	The novel genome data of HNhx	1280:1308	The novel genome data of HNhx will be helpful for understanding the evolution and epidemiology of PRRSV in China.
29090410	1	71	theme	respiratory	155:165	arg1	PRRSVs					185:190	PRRSVs	185:190	PRRSVs	185:190	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	1	71	theme	respiratory	155:165	arg1	viruses					176:182	NADC30-like porcine reproductive and respiratory syndrome viruses	118:182	NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs)	118:191	Recently, NADC30-like porcine reproductive and respiratory syndrome viruses (PRRSVs), which are genetically similar to the NADC30 strain isolated in the United States of America in 2008, have become prevalent in China.
29090410	7	72	theme	recombination	1135:1147	arg1	HNhx					1112:1115	HNhx	1112:1115	HNhx	1112:1115	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
29090410	7	72	theme	recombination	1135:1147	arg1	result					1125:1130	the result	1121:1130	the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911)	1121:1277	Recombination analysis revealed that HNhx was the result of recombination between the NADC30 strain and the highly pathogenic PRRSV vaccine strain circulating in China in Nsp4 (nt 5261) to Nsp9 (nt 7911).
28976803	1	0	dep	pathogen	269:276	arg1	neoformans					291:300	Cryptococcus neoformans	278:300	the opportunistic fungal pathogen Cryptococcus neoformans	244:300	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	6	1	theme	arg1Δ	1359:1363	arg1	phagocytosis					1365:1376	arg1Δ phagocytosis	1359:1376	arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model	1359:1465	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	5	2	theme	deleterious	944:954	arg1	phenotype					956:964	the most deleterious phenotype	935:964	the most deleterious phenotype	935:964	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	8	3	theme	PP-IP5-dependent	1679:1694	arg1	functions					1725:1733	PP-IP5-dependent and novel PP-IP5-independent functions	1679:1733	PP-IP5-dependent and novel PP-IP5-independent functions	1679:1733	In summary, we show that Arg1 is the most crucial IPK for cryptococcal virulence, conveying PP-IP5-dependent and novel PP-IP5-independent functions.
28976803	5	4	gly	mannosylation	1182:1194	arg1	factor					1213:1218	the virulence factor	1199:1218	the virulence factor	1199:1218	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	4	gly	mannosylation	1182:1194	arg1	B1					1235:1236	phospholipase B1	1221:1236	phospholipase B1	1221:1236	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	0	5	theme	neoformans	99:108	arg1	infection					110:118	Cryptococcus neoformans infection	86:118	Cryptococcus neoformans infection	86:118	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	6	6	theme	blood	1398:1402	arg1	monocytes					1404:1412	human peripheral blood monocytes	1381:1412	human peripheral blood monocytes	1381:1412	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	5	7	theme	normal	1166:1171	arg1	mannosylation					1182:1194	normal N-linked mannosylation	1166:1194	normal N-linked mannosylation	1166:1194	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	0	8	theme	Cryptococcus	86:97	arg1	neoformans					99:108	Cryptococcus neoformans	86:108	Cryptococcus neoformans infection	86:118	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	8	9	theme	novel	1700:1704	arg1	functions					1725:1733	PP-IP5-dependent and novel PP-IP5-independent functions	1679:1733	PP-IP5-dependent and novel PP-IP5-independent functions	1679:1733	In summary, we show that Arg1 is the most crucial IPK for cryptococcal virulence, conveying PP-IP5-dependent and novel PP-IP5-independent functions.
28976803	5	10	theme	kcs1Δ	865:869	arg1	mutants					880:886	kcs1Δ deletion mutants	865:886	kcs1Δ deletion mutants	865:886	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	11	theme	capsule	1118:1124	arg1	production					1126:1135	capsule production	1118:1135	capsule production	1118:1135	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	2	12	theme	key	442:444	arg1	metabolite					446:455	a key metabolite	440:455	a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain	440:542	Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain.
28976803	2	12	theme	key	442:444	arg1	PP-IP5					426:431	PP-IP5	426:431	PP-IP5 (IP7)	426:437	Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain.
28976803	3	13	theme	IP3/IP4	657:663	arg1	kinase					666:671	a dual specificity (IP3/IP4) kinase	637:671	a dual specificity (IP3/IP4) kinase producing IP5	637:685	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	3	13	theme	IP3/IP4	657:663	arg1	it					631:632	it	631:632	it	631:632	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	7	14	theme	chronic	1553:1559	arg1	infection					1576:1584	a chronic, confined lung infection	1551:1584	a chronic, confined lung infection	1551:1584	This observation is in contrast to kcs1Δ, which we previously reported establishes a chronic, confined lung infection.
28976803	5	15	theme	deletion	871:878	arg1	mutants					880:886	kcs1Δ deletion mutants	865:886	kcs1Δ deletion mutants	865:886	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	16	from	defective	1264:1272	arg1	arg1Δ					1282:1286	arg1Δ	1282:1286	arg1Δ	1282:1286	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	17	from	adaptation	1018:1027	arg1	strains					1044:1050	both mutant strains	1032:1050	both mutant strains	1032:1050	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	3	18	theme	dual	639:642	arg1	kinase					666:671	a dual specificity (IP3/IP4) kinase	637:671	a dual specificity (IP3/IP4) kinase producing IP5	637:685	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	3	18	theme	dual	639:642	arg1	it					631:632	it	631:632	it	631:632	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	7	19	dep	kcs1Δ	1503:1507	arg1	contrast					1491:1498	contrast	1491:1498	contrast	1491:1498	This observation is in contrast to kcs1Δ, which we previously reported establishes a chronic, confined lung infection.
28976803	5	20	theme	mutants	880:886	arg1	comparison					837:846	Phenotypic comparison	826:846	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient)	826:910	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	0	21	theme	kinase	6:11	arg1	Arg1					13:16	IP3-4 kinase Arg1	0:16	IP3-4 kinase Arg1	0:16	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	3	22	theme	specificity	644:654	arg1	kinase					666:671	a dual specificity (IP3/IP4) kinase	637:671	a dual specificity (IP3/IP4) kinase producing IP5	637:685	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	3	22	theme	specificity	644:654	arg1	it					631:632	it	631:632	it	631:632	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	8	23	theme	PP-IP5-independent	1706:1723	arg1	functions					1725:1733	PP-IP5-dependent and novel PP-IP5-independent functions	1679:1733	PP-IP5-dependent and novel PP-IP5-independent functions	1679:1733	In summary, we show that Arg1 is the most crucial IPK for cryptococcal virulence, conveying PP-IP5-dependent and novel PP-IP5-independent functions.
28976803	7	24	theme	lung	1571:1574	arg1	infection					1576:1584	a chronic, confined lung infection	1551:1584	a chronic, confined lung infection	1551:1584	This observation is in contrast to kcs1Δ, which we previously reported establishes a chronic, confined lung infection.
28976803	1	25	theme	inositol	175:182	arg1	Arg1					214:217	Arg1	214:217	Arg1	214:217	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	25	theme	inositol	175:182	arg1	Ipk1					220:223	Ipk1	220:223	Ipk1	220:223	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	25	theme	inositol	175:182	arg1	kinases					198:204	inositol polyphosphate kinases	175:204	inositol polyphosphate kinases (IPKs)	175:211	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	25	theme	inositol	175:182	arg1	IPKs					207:210	IPKs	207:210	IPKs	207:210	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	25	theme	inositol	175:182	arg1	Kcs1					226:229	Kcs1	226:229	Kcs1	226:229	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	25	theme	inositol	175:182	arg1	Asp1					235:238	Asp1	235:238	Asp1	235:238	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	0	26	theme	IP3-4	0:4	arg1	Arg1					13:16	IP3-4 kinase Arg1	0:16	IP3-4 kinase Arg1	0:16	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	5	27	theme	virulence	1203:1211	arg1	factor					1213:1218	the virulence factor	1199:1218	the virulence factor	1199:1218	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	27	theme	virulence	1203:1211	arg1	B1					1235:1236	phospholipase B1	1221:1236	phospholipase B1	1221:1236	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	1	28	theme	polyphosphate	184:196	arg1	Arg1					214:217	Arg1	214:217	Arg1	214:217	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	28	theme	polyphosphate	184:196	arg1	Ipk1					220:223	Ipk1	220:223	Ipk1	220:223	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	28	theme	polyphosphate	184:196	arg1	kinases					198:204	inositol polyphosphate kinases	175:204	inositol polyphosphate kinases (IPKs)	175:211	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	28	theme	polyphosphate	184:196	arg1	IPKs					207:210	IPKs	207:210	IPKs	207:210	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	28	theme	polyphosphate	184:196	arg1	Kcs1					226:229	Kcs1	226:229	Kcs1	226:229	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	1	28	theme	polyphosphate	184:196	arg1	Asp1					235:238	Asp1	235:238	Asp1	235:238	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	2	29	theme	metabolic	485:493	arg1	adaptation					495:504	metabolic adaptation	485:504	metabolic adaptation	485:504	Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain.
28976803	5	30	theme	factor	1213:1218	arg1	mannosylation					1182:1194	normal N-linked mannosylation	1166:1194	normal N-linked mannosylation	1166:1194	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	30	theme	factor	1213:1218	arg1	organization					1148:1159	cell wall organization	1138:1159	cell wall organization	1138:1159	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	30	theme	factor	1213:1218	arg1	production					1126:1135	capsule production	1118:1135	capsule production	1118:1135	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	1	31	theme	kinases	198:204	arg1	series					165:170	a series	163:170	a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1,	163:239	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	6	32	theme	higher	1344:1349	arg1	rate					1351:1354	a higher rate	1342:1354	a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model	1342:1465	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	3	33	theme	enzymatic	584:592	arg1	activity					594:601	the enzymatic activity	580:601	the enzymatic activity of Arg1	580:609	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	5	34	theme	arg1Δ	855:859	arg1	comparison					837:846	Phenotypic comparison	826:846	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient)	826:910	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	6	35	theme	arg1Δ	1424:1428	arg1	clearance					1430:1438	rapid arg1Δ clearance	1418:1438	rapid arg1Δ clearance	1418:1438	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	0	36	theme	wall	33:36	arg1	homeostasis					38:48	cell wall homeostasis	28:48	cell wall homeostasis	28:48	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	1	37	theme	opportunistic	248:260	arg1	pathogen					269:276	the opportunistic fungal pathogen Cryptococcus neoformans	244:300	the opportunistic fungal pathogen Cryptococcus neoformans	244:300	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	7	38	dep	chronic	1553:1559	arg1	confined					1562:1569	confined	1562:1569	confined	1562:1569	This observation is in contrast to kcs1Δ, which we previously reported establishes a chronic, confined lung infection.
28976803	5	39	theme	phospholipase	1221:1233	arg1	factor					1213:1218	the virulence factor	1199:1218	the virulence factor	1199:1218	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	39	theme	phospholipase	1221:1233	arg1	B1					1235:1236	phospholipase B1	1221:1236	phospholipase B1	1221:1236	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	0	40	theme	cell	28:31	arg1	homeostasis					38:48	cell wall homeostasis	28:48	cell wall homeostasis	28:48	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	1	41	theme	fungal	262:267	arg1	pathogen					269:276	the opportunistic fungal pathogen Cryptococcus neoformans	244:300	the opportunistic fungal pathogen Cryptococcus neoformans	244:300	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	2	42	theme	stress	467:472	arg1	tolerance					474:482	stress tolerance	467:482	stress tolerance	467:482	Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain.
28976803	5	43	theme	virulence-associated	1079:1098	arg1	mannosylation					1182:1194	normal N-linked mannosylation	1166:1194	normal N-linked mannosylation	1166:1194	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	43	theme	virulence-associated	1079:1098	arg1	functions					1100:1108	virulence-associated functions	1079:1108	virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1	1079:1236	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	43	theme	virulence-associated	1079:1098	arg1	organization					1148:1159	cell wall organization	1138:1159	cell wall organization	1138:1159	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	43	theme	virulence-associated	1079:1098	arg1	production					1126:1135	capsule production	1118:1135	capsule production	1118:1135	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	44	from	arg1Δ	1282:1286	arg1	defective					1264:1272	defective	1264:1272	defective	1264:1272	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	6	45	theme	deleterious	1298:1308	arg1	phenotype					1316:1324	The more deleterious arg1Δ phenotype	1289:1324	The more deleterious arg1Δ phenotype	1289:1324	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	5	46	theme	mutant	1037:1042	arg1	strains					1044:1050	both mutant strains	1032:1050	both mutant strains	1032:1050	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	47	theme	metabolic	997:1005	arg1	adaptation					1018:1027	metabolic and stress adaptation	997:1027	adaptation	1018:1027	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	2	48	theme	deletion	314:321	arg1	analysis					323:330	gene deletion analysis	309:330	gene deletion analysis	309:330	Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain.
28976803	0	49	theme	mouse	125:129	arg1	model					131:135	a mouse model	123:135	a mouse model	123:135	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	1	50	theme	Cryptococcus	278:289	arg1	neoformans					291:300	Cryptococcus neoformans	278:300	the opportunistic fungal pathogen Cryptococcus neoformans	244:300	We previously identified a series of inositol polyphosphate kinases (IPKs), Arg1, Ipk1, Kcs1 and Asp1, in the opportunistic fungal pathogen Cryptococcus neoformans.
28976803	2	51	theme	fungal	510:515	arg1	dissemination					517:529	fungal dissemination	510:529	fungal dissemination	510:529	Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain.
28976803	5	52	theme	N-linked	1173:1180	arg1	mannosylation					1182:1194	normal N-linked mannosylation	1166:1194	normal N-linked mannosylation	1166:1194	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	2	53	theme	gene	309:312	arg1	analysis					323:330	gene deletion analysis	309:330	gene deletion analysis	309:330	Using gene deletion analysis, we characterized Arg1, Ipk1 and Kcs1 and showed that they act sequentially to convert IP3 to PP-IP5 (IP7), a key metabolite promoting stress tolerance, metabolic adaptation and fungal dissemination to the brain.
28976803	5	54	contain	has	931:933	arg2	phenotype					956:964	the most deleterious phenotype	935:964	the most deleterious phenotype	935:964	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	54	contain	has	931:933	arg1	arg1Δ					925:929	arg1Δ	925:929	arg1Δ	925:929	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	6	55	theme	arg1Δ	1310:1314	arg1	phenotype					1316:1324	The more deleterious arg1Δ phenotype	1289:1324	The more deleterious arg1Δ phenotype	1289:1324	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	4	56	theme	PP-IP5	810:815	arg1	synthesis					797:805	the synthesis	793:805	the synthesis of PP-IP5 by Kcs1	793:823	We showed previously that IP5 is further phosphorylated by Ipk1 to produce IP6, which is a substrate for the synthesis of PP-IP5 by Kcs1.
28976803	6	57	theme	rapid	1418:1422	arg1	clearance					1430:1438	rapid arg1Δ clearance	1418:1438	rapid arg1Δ clearance	1418:1438	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	8	58	theme	crucial	1629:1635	arg1	IPK					1637:1639	the most crucial IPK	1620:1639	the most crucial IPK for cryptococcal virulence	1620:1666	In summary, we show that Arg1 is the most crucial IPK for cryptococcal virulence, conveying PP-IP5-dependent and novel PP-IP5-independent functions.
28976803	8	58	theme	crucial	1629:1635	arg1	Arg1					1612:1615	Arg1	1612:1615	Arg1	1612:1615	In summary, we show that Arg1 is the most crucial IPK for cryptococcal virulence, conveying PP-IP5-dependent and novel PP-IP5-independent functions.
28976803	6	59	theme	peripheral	1387:1396	arg1	monocytes					1404:1412	human peripheral blood monocytes	1381:1412	human peripheral blood monocytes	1381:1412	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	6	60	from	lung	1445:1448	arg1	model					1461:1465	a mouse model	1453:1465	a mouse model	1453:1465	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	6	60	from	lung	1445:1448	arg1	monocytes					1404:1412	human peripheral blood monocytes	1381:1412	human peripheral blood monocytes	1381:1412	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	6	60	from	lung	1445:1448	arg1	clearance					1430:1438	rapid arg1Δ clearance	1418:1438	rapid arg1Δ clearance	1418:1438	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	5	61	link	N-linked	1173:1180	arg1	mannosylation					1182:1194	normal N-linked mannosylation	1166:1194	normal N-linked mannosylation	1166:1194	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	8	62	theme	cryptococcal	1645:1656	arg1	virulence					1658:1666	cryptococcal virulence	1645:1666	cryptococcal virulence	1645:1666	In summary, we show that Arg1 is the most crucial IPK for cryptococcal virulence, conveying PP-IP5-dependent and novel PP-IP5-independent functions.
28976803	5	63	theme	Phenotypic	826:835	arg1	comparison					837:846	Phenotypic comparison	826:846	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient)	826:910	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	6	64	theme	human	1381:1385	arg1	monocytes					1404:1412	human peripheral blood monocytes	1381:1412	human peripheral blood monocytes	1381:1412	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	3	65	theme	Arg1	606:609	arg1	activity					594:601	the enzymatic activity	580:601	the enzymatic activity of Arg1	580:609	We have now directly characterized the enzymatic activity of Arg1, demonstrating that it is a dual specificity (IP3/IP4) kinase producing IP5.
28976803	5	66	dep	PP-IP5-deficient	894:909	arg1	both					889:892	both	889:892	both	889:892	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	67	theme	cell	1138:1141	arg1	organization					1148:1159	cell wall organization	1138:1159	cell wall organization	1138:1159	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	0	68	theme	surface	54:60	arg1	architecture					62:73	surface architecture	54:73	surface architecture	54:73	IP3-4 kinase Arg1 regulates cell wall homeostasis and surface architecture to promote Cryptococcus neoformans infection in a mouse model.
28976803	5	69	theme	stress	1011:1016	arg1	adaptation					1018:1027	metabolic and stress adaptation	997:1027	adaptation	1018:1027	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	6	70	theme	mouse	1455:1459	arg1	model					1461:1465	a mouse model	1453:1465	a mouse model	1453:1465	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	5	71	dep	arg1Δ	855:859	arg1	the					851:853	the	851:853	the	851:853	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	5	71	dep	arg1Δ	855:859	arg1	PP-IP5-deficient					894:909	PP-IP5-deficient	894:909	PP-IP5-deficient	894:909	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28976803	6	72	theme	phagocytosis	1365:1376	arg1	rate					1351:1354	a higher rate	1342:1354	a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model	1342:1465	The more deleterious arg1Δ phenotype correlated with a higher rate of arg1Δ phagocytosis by human peripheral blood monocytes and rapid arg1Δ clearance from lung in a mouse model.
28976803	5	73	theme	wall	1143:1146	arg1	organization					1148:1159	cell wall organization	1138:1159	cell wall organization	1138:1159	Phenotypic comparison of the arg1Δ and kcs1Δ deletion mutants (both PP-IP5-deficient) reveals that arg1Δ has the most deleterious phenotype: while PP-IP5 is essential for metabolic and stress adaptation in both mutant strains, PP-IP5 is dispensable for virulence-associated functions such as capsule production, cell wall organization, and normal N-linked mannosylation of the virulence factor, phospholipase B1, as these phenotypes were defective only in arg1Δ.
28474196	4	0	theme	highest	932:938	arg1	level					961:965	The highest messenger RNA (mRNA) level	928:965	The highest messenger RNA (mRNA) level of FBP1b	928:974	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	3	1	theme	phosphorylation	764:778	arg1	sites					780:784	13 phosphorylation sites	761:784	13 phosphorylation sites	761:784	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	3	2	theme	high	609:612	arg1	degree					614:619	a high degree	607:619	a high degree of conservation (76-96%) among most fish and other vertebrates	607:682	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	8	3	theme	mRNA	1657:1660	arg1	levels					1662:1667	the mRNA levels	1653:1667	the mRNA levels	1653:1667	In addition, both the mRNA levels and activities decreased significantly with increasing dietary carbohydrate levels.
28474196	1	4	theme	1b	313:314	arg1	cDNA					276:279	cDNA	276:279	cDNA	276:279	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	1	4	theme	1b	313:314	arg1	DNA					271:273	the full-length complementary DNA	241:273	the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala	241:357	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	10	5	theme	glucose	1933:1939	arg1	administration					1941:1954	a glucose administration	1931:1954	a glucose administration	1931:1954	Its mRNA expression in liver was downregulated remarkably by a glucose administration, as also held true after the long-term adaptation of a carbohydrate-rich diet.
28474196	1	6	theme	high-carbohydrate	455:471	arg1	diets					473:477	high-carbohydrate diets	455:477	high-carbohydrate diets	455:477	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	10	7	from	expression	1879:1888	arg1	liver					1893:1897	liver	1893:1897	liver	1893:1897	Its mRNA expression in liver was downregulated remarkably by a glucose administration, as also held true after the long-term adaptation of a carbohydrate-rich diet.
28474196	0	8	theme	glucose	143:149	arg1	loading					151:157	glucose loading	143:157	glucose loading	143:157	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	4	9	theme	FBP1b	970:974	arg1	level					961:965	The highest messenger RNA (mRNA) level	928:965	The highest messenger RNA (mRNA) level of FBP1b	928:974	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	0	10	from	amblycephala	94:105	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.	0:206	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	3	11	theme	active	828:833	arg1	site					835:838	one fructose-1,6-bisphosphatase (FBPase) active site	787:838	one fructose-1,6-bisphosphatase (FBPase) active site	787:838	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	8	12	theme	dietary	1724:1730	arg1	levels					1745:1750	dietary carbohydrate levels	1724:1750	dietary carbohydrate levels	1724:1750	In addition, both the mRNA levels and activities decreased significantly with increasing dietary carbohydrate levels.
28474196	1	13	theme	full-length	245:255	arg1	cDNA					276:279	cDNA	276:279	cDNA	276:279	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	1	13	theme	full-length	245:255	arg1	DNA					271:273	the full-length complementary DNA	241:273	the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala	241:357	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	4	14	theme	RNA	950:952	arg1	level					961:965	The highest messenger RNA (mRNA) level	928:965	The highest messenger RNA (mRNA) level of FBP1b	928:974	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	6	15	from	levels	1367:1372	arg1	treatments					1391:1400	both treatments	1386:1400	both treatments	1386:1400	After the glucose load, the mRNA levels of FBP1b in both treatments decreased significantly to the basal value at 8 h and showed a slight increase afterward.
28474196	3	16	theme	several	901:907	arg1	sites					921:925	several AMP-binding sites	901:925	several AMP-binding sites	901:925	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	7	17	theme	first	1568:1572	arg1	4 h					1574:1576	the first 4 h	1564:1576	the first 4 h	1564:1576	However, the enzymatic activity showed no statistical difference during the first 4 h, but increased remarkably with further increasing times.
28474196	0	18	from	response	131:138	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.	0:206	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	3	19	theme	metal-binding	846:858	arg1	sites					860:864	five metal-binding sites	841:864	five metal-binding sites	841:864	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	3	19	theme	metal-binding	846:858	arg1	sites					890:894	four substrate-binding sites	867:894	four substrate-binding sites	867:894	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	0	20	theme	high-carbohydrate	183:199	arg1	diets					201:205	high-carbohydrate diets	183:205	high-carbohydrate diets	183:205	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	3	21	theme	other	666:670	arg1	vertebrates					672:682	other vertebrates	666:682	other vertebrates	666:682	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	4	22	located	observed	980:987	arg2	level					961:965	The highest messenger RNA (mRNA) level	928:965	The highest messenger RNA (mRNA) level of FBP1b	928:974	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	4	22	located	observed	980:987	arg1	liver					992:996	liver	992:996	liver followed by intestine	992:1018	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	5	23	theme	carbohydrate	1287:1298	arg1	%					1317:1317	30 and 42%	1308:1317	30 and 42%	1308:1317	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	5	23	theme	carbohydrate	1287:1298	arg1	levels					1300:1305	two dietary carbohydrate levels	1275:1305	two dietary carbohydrate levels (30 and 42%)	1275:1318	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	0	24	theme	bream	76:80	arg1	amblycephala					94:105	blunt snout bream Megalobrama amblycephala	64:105	blunt snout bream Megalobrama amblycephala	64:105	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	5	25	theme	FBP1b	1115:1119	arg1	levels					1105:1110	the mRNA levels	1096:1110	the mRNA levels of FBP1b	1096:1119	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	5	25	theme	FBP1b	1115:1119	arg1	activity					1136:1143	the FBPase activity	1125:1143	the FBPase activity	1125:1143	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	7	26	theme	statistical	1534:1544	arg1	difference					1546:1555	no statistical difference	1531:1555	no statistical difference	1531:1555	However, the enzymatic activity showed no statistical difference during the first 4 h, but increased remarkably with further increasing times.
28474196	3	27	theme	substrate-binding	872:888	arg1	sites					860:864	five metal-binding sites	841:864	five metal-binding sites	841:864	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	3	27	theme	substrate-binding	872:888	arg1	sites					890:894	four substrate-binding sites	867:894	four substrate-binding sites	867:894	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	6	28	theme	glucose	1344:1350	arg1	load					1352:1355	the glucose load	1340:1355	the glucose load	1340:1355	After the glucose load, the mRNA levels of FBP1b in both treatments decreased significantly to the basal value at 8 h and showed a slight increase afterward.
28474196	4	29	located	detected	1056:1063	arg2	values					1044:1049	relatively low values	1029:1049	relatively low values	1029:1049	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	4	29	located	detected	1056:1063	arg1	gill					1075:1078	gill	1075:1078	gill	1075:1078	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	4	29	located	detected	1056:1063	arg1	eye					1085:1087	eye	1085:1087	eye	1085:1087	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	4	29	located	detected	1056:1063	arg1	heart					1068:1072	heart	1068:1072	heart	1068:1072	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	7	30	theme	enzymatic	1505:1513	arg1	activity					1515:1522	the enzymatic activity	1501:1522	the enzymatic activity	1501:1522	However, the enzymatic activity showed no statistical difference during the first 4 h, but increased remarkably with further increasing times.
28474196	1	31	theme	glucose	408:414	arg1	administration					416:429	glucose administration	408:429	glucose administration	408:429	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	0	32	from	1b	58:59	arg1	amblycephala					94:105	blunt snout bream Megalobrama amblycephala	64:105	blunt snout bream Megalobrama amblycephala	64:105	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	0	32	from	1b	58:59	arg1	response					131:138	the transcriptional response	111:138	the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets	111:205	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	0	33	theme	Molecular	0:8	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.	0:206	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	7	34	theme	further	1609:1615	arg1	times					1628:1632	further increasing times	1609:1632	further increasing times	1609:1632	However, the enzymatic activity showed no statistical difference during the first 4 h, but increased remarkably with further increasing times.
28474196	2	35	theme	reading	527:533	arg1	frame					535:539	an open reading frame	519:539	an open reading frame of 1014 bp	519:550	The cDNA obtained covered 1435 bp with an open reading frame of 1014 bp.
28474196	0	36	theme	1b	58:59	arg1	characterization					10:25	Molecular characterization	0:25	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.	0:206	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	1	37	theme	fish	329:332	arg1	amblycephala					346:357	fish Megalobrama amblycephala	329:357	fish Megalobrama amblycephala	329:357	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	2	38	theme	open	522:525	arg1	frame					535:539	an open reading frame	519:539	an open reading frame of 1014 bp	519:550	The cDNA obtained covered 1435 bp with an open reading frame of 1014 bp.
28474196	0	39	theme	blunt	64:68	arg1	amblycephala					94:105	blunt snout bream Megalobrama amblycephala	64:105	blunt snout bream Megalobrama amblycephala	64:105	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	6	40	from	8 h	1448:1450	arg1	value					1439:1443	the basal value	1429:1443	the basal value at 8 h	1429:1450	After the glucose load, the mRNA levels of FBP1b in both treatments decreased significantly to the basal value at 8 h and showed a slight increase afterward.
28474196	9	41	theme	high	1818:1821	arg1	similarity					1823:1832	a high similarity	1816:1832	a high similarity with that of the other vertebrates	1816:1867	The results indicated that the FBP1b of M. amblycephala shared a high similarity with that of the other vertebrates.
28474196	5	42	theme	1.67 g	1219:1224	arg1	glucose					1226:1232	1.67 g glucose	1219:1232	1.67 g glucose per kilogram body weight	1219:1257	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	10	43	theme	diet	2029:2032	arg1	adaptation					1995:2004	the long-term adaptation	1981:2004	the long-term adaptation of a carbohydrate-rich diet	1981:2032	Its mRNA expression in liver was downregulated remarkably by a glucose administration, as also held true after the long-term adaptation of a carbohydrate-rich diet.
28474196	3	44	theme	glycosylation	708:720	arg1	site					722:725	one N-linked glycosylation site	695:725	one N-linked glycosylation site	695:725	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	10	45	theme	mRNA	1874:1877	arg1	expression					1879:1888	Its mRNA expression	1870:1888	Its mRNA expression in liver	1870:1897	Its mRNA expression in liver was downregulated remarkably by a glucose administration, as also held true after the long-term adaptation of a carbohydrate-rich diet.
28474196	1	46	from	amblycephala	346:357	arg1	cDNA					276:279	cDNA	276:279	cDNA	276:279	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	1	46	from	amblycephala	346:357	arg1	DNA					271:273	the full-length complementary DNA	241:273	the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala	241:357	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	3	47	theme	Sequence	553:560	arg1	alignment					562:570	Sequence alignment	553:570	Sequence alignment	553:570	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	5	48	theme	fish	1182:1185	arg1	liver					1173:1177	the liver	1169:1177	the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight	1169:1257	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	9	49	theme	other	1851:1855	arg1	vertebrates					1857:1867	the other vertebrates	1847:1867	the other vertebrates	1847:1867	The results indicated that the FBP1b of M. amblycephala shared a high similarity with that of the other vertebrates.
28474196	3	50	theme	N-terminal	732:741	arg1	site					755:758	one N-terminal acetylation site	728:758	one N-terminal acetylation site	728:758	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	1	51	theme	fructose-1,6-bisphosphatase	285:311	arg1	FBP1b					317:321	FBP1b	317:321	FBP1b	317:321	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	1	51	theme	fructose-1,6-bisphosphatase	285:311	arg1	1b					313:314	fructose-1,6-bisphosphatase 1b	285:314	fructose-1,6-bisphosphatase 1b (FBP1b)	285:322	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	6	52	theme	mRNA	1362:1365	arg1	levels					1367:1372	the mRNA levels	1358:1372	the mRNA levels of FBP1b in both treatments	1358:1400	After the glucose load, the mRNA levels of FBP1b in both treatments decreased significantly to the basal value at 8 h and showed a slight increase afterward.
28474196	9	53	with	similarity	1823:1832	arg1	that					1839:1842	that	1839:1842	that	1839:1842	The results indicated that the FBP1b of M. amblycephala shared a high similarity with that of the other vertebrates.
28474196	3	54	theme	fructose-1,6-bisphosphatase	791:817	arg1	site					835:838	one fructose-1,6-bisphosphatase (FBPase) active site	787:838	one fructose-1,6-bisphosphatase (FBPase) active site	787:838	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	3	55	theme	conservation	624:635	arg1	degree					614:619	a high degree	607:619	a high degree of conservation (76-96%) among most fish and other vertebrates	607:682	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	6	56	theme	slight	1465:1470	arg1	increase					1472:1479	a slight increase	1463:1479	a slight increase	1463:1479	After the glucose load, the mRNA levels of FBP1b in both treatments decreased significantly to the basal value at 8 h and showed a slight increase afterward.
28474196	3	57	link	N-linked	699:706	arg1	site					722:725	one N-linked glycosylation site	695:725	one N-linked glycosylation site	695:725	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	5	58	theme	FBPase	1129:1134	arg1	activity					1136:1143	the FBPase activity	1125:1143	the FBPase activity	1125:1143	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	4	59	theme	messenger	940:948	arg1	mRNA					955:958	mRNA	955:958	mRNA	955:958	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	4	59	theme	messenger	940:948	arg1	RNA					950:952	messenger RNA	940:952	The highest messenger RNA (mRNA) level of FBP1b	928:974	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	8	60	theme	carbohydrate	1732:1743	arg1	levels					1745:1750	dietary carbohydrate levels	1724:1750	dietary carbohydrate levels	1724:1750	In addition, both the mRNA levels and activities decreased significantly with increasing dietary carbohydrate levels.
28474196	3	61	theme	AMP-binding	909:919	arg1	sites					921:925	several AMP-binding sites	901:925	several AMP-binding sites	901:925	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	5	62	theme	dietary	1279:1285	arg1	%					1317:1317	30 and 42%	1308:1317	30 and 42%	1308:1317	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	5	62	theme	dietary	1279:1285	arg1	levels					1300:1305	two dietary carbohydrate levels	1275:1305	two dietary carbohydrate levels (30 and 42%)	1275:1318	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	0	63	theme	Megalobrama	82:92	arg1	amblycephala					94:105	blunt snout bream Megalobrama amblycephala	64:105	blunt snout bream Megalobrama amblycephala	64:105	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	3	64	theme	most	652:655	arg1	fish					657:660	most fish	652:660	most fish	652:660	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	2	65	theme	1014 bp	544:550	arg1	frame					535:539	an open reading frame	519:539	an open reading frame of 1014 bp	519:550	The cDNA obtained covered 1435 bp with an open reading frame of 1014 bp.
28474196	1	66	theme	complementary	257:269	arg1	cDNA					276:279	cDNA	276:279	cDNA	276:279	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	1	66	theme	complementary	257:269	arg1	DNA					271:273	the full-length complementary DNA	241:273	the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala	241:357	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	5	67	theme	body	1247:1250	arg1	weight					1252:1257	kilogram body weight	1238:1257	kilogram body weight	1238:1257	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	0	68	from	characterization	10:25	arg1	amblycephala					94:105	blunt snout bream Megalobrama amblycephala	64:105	blunt snout bream Megalobrama amblycephala	64:105	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	0	68	from	characterization	10:25	arg1	response					131:138	the transcriptional response	111:138	the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets	111:205	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	0	69	theme	transcriptional	115:129	arg1	response					131:138	the transcriptional response	111:138	the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets	111:205	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	1	70	theme	transcriptional	380:394	arg1	response					396:403	its transcriptional response	376:403	its transcriptional response to glucose administration	376:429	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	10	71	theme	long-term	1985:1993	arg1	adaptation					1995:2004	the long-term adaptation	1981:2004	the long-term adaptation of a carbohydrate-rich diet	1981:2032	Its mRNA expression in liver was downregulated remarkably by a glucose administration, as also held true after the long-term adaptation of a carbohydrate-rich diet.
28474196	5	72	theme	mRNA	1100:1103	arg1	levels					1105:1110	the mRNA levels	1096:1110	the mRNA levels of FBP1b	1096:1119	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
28474196	0	73	theme	fructose-1,6-bisphosphatase	30:56	arg1	1b					58:59	fructose-1,6-bisphosphatase 1b	30:59	fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets	30:205	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	6	74	theme	FBP1b	1377:1381	arg1	levels					1367:1372	the mRNA levels	1358:1372	the mRNA levels of FBP1b in both treatments	1358:1400	After the glucose load, the mRNA levels of FBP1b in both treatments decreased significantly to the basal value at 8 h and showed a slight increase afterward.
28474196	7	75	theme	increasing	1617:1626	arg1	times					1628:1632	further increasing times	1609:1632	further increasing times	1609:1632	However, the enzymatic activity showed no statistical difference during the first 4 h, but increased remarkably with further increasing times.
28474196	9	76	theme	amblycephala	1796:1807	arg1	FBP1b					1784:1788	the FBP1b	1780:1788	the FBP1b of M. amblycephala	1780:1807	The results indicated that the FBP1b of M. amblycephala shared a high similarity with that of the other vertebrates.
28474196	0	77	theme	snout	70:74	arg1	amblycephala					94:105	blunt snout bream Megalobrama amblycephala	64:105	blunt snout bream Megalobrama amblycephala	64:105	Molecular characterization of fructose-1,6-bisphosphatase 1b in blunt snout bream Megalobrama amblycephala and the transcriptional response to glucose loading after the adaptation to high-carbohydrate diets.
28474196	1	78	theme	Megalobrama	334:344	arg1	amblycephala					346:357	fish Megalobrama amblycephala	329:357	fish Megalobrama amblycephala	329:357	This study aimed to characterize the full-length complementary DNA (cDNA) of fructose-1,6-bisphosphatase 1b (FBP1b) from fish Megalobrama amblycephala, and investigate its transcriptional response to glucose administration after the adaptation to high-carbohydrate diets.
28474196	4	79	theme	low	1040:1042	arg1	values					1044:1049	relatively low values	1029:1049	relatively low values	1029:1049	The highest messenger RNA (mRNA) level of FBP1b was observed in liver followed by intestine, whereas relatively low values were detected in heart, gill, and eye.
28474196	3	80	theme	N-linked	699:706	arg1	site					722:725	one N-linked glycosylation site	695:725	one N-linked glycosylation site	695:725	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	10	81	theme	carbohydrate-rich	2011:2027	arg1	diet					2029:2032	a carbohydrate-rich diet	2009:2032	a carbohydrate-rich diet	2009:2032	Its mRNA expression in liver was downregulated remarkably by a glucose administration, as also held true after the long-term adaptation of a carbohydrate-rich diet.
28474196	3	82	gly	glycosylation	708:720	arg2	site					722:725	one N-linked glycosylation site	695:725	one N-linked glycosylation site	695:725	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	3	82	gly	glycosylation	708:720	arg2	one					695:697	one	695:697	one	695:697	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	3	83	theme	acetylation	743:753	arg1	site					755:758	one N-terminal acetylation site	728:758	one N-terminal acetylation site	728:758	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	3	84	theme	phylogenetic	576:587	arg1	analysis					589:596	phylogenetic analysis	576:596	phylogenetic analysis	576:596	Sequence alignment and phylogenetic analysis revealed a high degree of conservation (76-96%) among most fish and other vertebrates, retaining one N-linked glycosylation site, one N-terminal acetylation site, 13 phosphorylation sites, one fructose-1,6-bisphosphatase (FBPase) active site, five metal-binding sites, four substrate-binding sites, and several AMP-binding sites.
28474196	6	85	theme	basal	1433:1437	arg1	value					1439:1443	the basal value	1429:1443	the basal value at 8 h	1429:1450	After the glucose load, the mRNA levels of FBP1b in both treatments decreased significantly to the basal value at 8 h and showed a slight increase afterward.
28474196	5	86	theme	kilogram	1238:1245	arg1	weight					1252:1257	kilogram body weight	1238:1257	kilogram body weight	1238:1257	Then, the mRNA levels of FBP1b and the FBPase activity were both determined in the liver of fish injected intraperitoneally with 1.67 g glucose per kilogram body weight after being fed two dietary carbohydrate levels (30 and 42%) for 11 weeks.
30083263	5	0	theme	Tid1-interacting	671:686	arg1	proteins					695:702	Tid1-interacting client proteins	671:702	Tid1-interacting client proteins	671:702	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	7	1	theme	protein	919:925	arg1	partner					862:868	interacting partner	850:868	interacting partner	850:868	The interacting partner and downstream target of Tid1-interacting client protein were determined.
30083263	7	1	theme	protein	919:925	arg1	target					885:890	downstream target	874:890	downstream target	874:890	The interacting partner and downstream target of Tid1-interacting client protein were determined.
30083263	12	2	theme	poor	1521:1524	arg1	rate					1535:1538	a poor survival rate	1519:1538	a poor survival rate	1519:1538	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	5	3	theme	proteins	695:702	arg1	profile					660:666	the expression profile	645:666	the expression profile of Tid1-interacting client proteins	645:702	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	7	4	theme	Tid1-interacting	895:910	arg1	protein					919:925	Tid1-interacting client protein	895:925	Tid1-interacting client protein	895:925	The interacting partner and downstream target of Tid1-interacting client protein were determined.
30083263	8	5	theme	client	1027:1032	arg1	proteins					1034:1041	the Tid1-interacting client proteins	1006:1041	the Tid1-interacting client proteins	1006:1041	Results: Herein, we first revealed that Galectin-7 was one of the Tid1-interacting client proteins.
30083263	6	6	from	roles	748:752	arg1	metastasis					793:802	metastasis	793:802	metastasis	793:802	The roles of Tid1-interacting client proteins in metastasis were validated both in vitro and in vivo.
30083263	5	7	from	staining	554:561	arg1	tissues					588:594	HNSCC patient tissues	574:594	HNSCC patient tissues	574:594	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	12	8	theme	Galectin-7	1500:1509	arg1	levels					1490:1495	increased protein levels	1472:1495	increased protein levels of Galectin-7	1472:1509	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	2	9	theme	neck	287:290	arg1	malignancy					324:333	head and neck squamous cell carcinoma (HNSCC) malignancy	278:333	head and neck squamous cell carcinoma (HNSCC) malignancy	278:333	Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy.
30083263	1	10	theme	co-chaperone	173:184	arg1	disc					153:156	Human tumorous imaginal disc	129:156	Human tumorous imaginal disc (Tid1)	129:163	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	10	theme	co-chaperone	173:184	arg1	protein					186:192	a DnaJ co-chaperone protein	166:192	a DnaJ co-chaperone protein	166:192	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	2	11	theme	head	278:281	arg1	malignancy					324:333	head and neck squamous cell carcinoma (HNSCC) malignancy	278:333	head and neck squamous cell carcinoma (HNSCC) malignancy	278:333	Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy.
30083263	7	12	theme	interacting	850:860	arg1	partner					862:868	interacting partner	850:868	interacting partner	850:868	The interacting partner and downstream target of Tid1-interacting client protein were determined.
30083263	12	13	theme	increased	1472:1480	arg1	levels					1490:1495	increased protein levels	1472:1495	increased protein levels of Galectin-7	1472:1509	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	5	14	with	association	625:635	arg1	features					720:727	pathologic features	709:727	pathologic features	709:727	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	5	14	with	association	625:635	arg1	prognosis					733:741	prognosis	733:741	prognosis	733:741	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	4	15	theme	affinity	433:440	arg1	chromatography					442:455	affinity chromatography	433:455	affinity chromatography	433:455	Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins.
30083263	14	16	theme	metastatic	1770:1779	arg1	progression					1781:1791	metastatic progression	1770:1791	metastatic progression	1770:1791	Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.
30083263	5	17	theme	pathologic	709:718	arg1	features					720:727	pathologic features	709:727	pathologic features	709:727	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	14	18	theme	MMP-9	1882:1886	arg1	expression					1888:1897	MMP-9 expression	1882:1897	MMP-9 expression	1882:1897	Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.
30083263	1	19	theme	Human	129:133	arg1	suppressor					220:229	a tumor suppressor	212:229	a tumor suppressor	212:229	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	19	theme	Human	129:133	arg1	Tid1					159:162	Tid1	159:162	Tid1	159:162	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	19	theme	Human	129:133	arg1	protein					186:192	a DnaJ co-chaperone protein	166:192	a DnaJ co-chaperone protein	166:192	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	19	theme	Human	129:133	arg1	disc					153:156	Human tumorous imaginal disc	129:156	Human tumorous imaginal disc (Tid1)	129:163	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	12	20	theme	4NQO	1446:1449	arg1	treatment					1452:1460	4-nitroquinoline-1-oxide (4NQO) treatment	1420:1460	4-nitroquinoline-1-oxide (4NQO) treatment	1420:1460	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	9	21	theme	protein	1070:1076	arg1	profile					1089:1095	protein expression profile	1070:1095	protein expression profile	1070:1095	An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients.
30083263	13	22	theme	Galectin-7	1679:1688	arg1	ubiquitination					1633:1646	Tid1-mediated ubiquitination	1619:1646	Tid1-mediated ubiquitination	1619:1646	Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7.
30083263	13	22	theme	Galectin-7	1679:1688	arg1	degradation					1664:1674	proteasomal degradation	1652:1674	proteasomal degradation	1652:1674	Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7.
30083263	1	23	theme	imaginal	144:151	arg1	suppressor					220:229	a tumor suppressor	212:229	a tumor suppressor	212:229	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	23	theme	imaginal	144:151	arg1	Tid1					159:162	Tid1	159:162	Tid1	159:162	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	23	theme	imaginal	144:151	arg1	protein					186:192	a DnaJ co-chaperone protein	166:192	a DnaJ co-chaperone protein	166:192	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	23	theme	imaginal	144:151	arg1	disc					153:156	Human tumorous imaginal disc	129:156	Human tumorous imaginal disc (Tid1)	129:163	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	9	24	theme	profile	1089:1095	arg1	association					1055:1065	An inverse association	1044:1065	An inverse association of protein expression profile between Tid1 and Galectin-7	1044:1123	An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients.
30083263	14	25	theme	transcription	1843:1855	arg1	factor					1857:1862	TCF3 transcription factor	1838:1862	TCF3 transcription factor	1838:1862	Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.
30083263	5	26	theme	Immunohistochemical	534:552	arg1	staining					554:561	Immunohistochemical staining	534:561	Immunohistochemical staining of Tid1 in HNSCC patient tissues	534:594	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	14	27	theme	critical	1725:1732	arg1	role					1734:1737	a critical role	1723:1737	a critical role	1723:1737	Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.
30083263	4	28	used	used	428:431	arg2	We					425:426	We	425:426	We	425:426	Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins.
30083263	4	29	theme	Tid1-interacting	500:515	arg1	proteins					524:531	Tid1-interacting client proteins	500:531	Tid1-interacting client proteins	500:531	Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins.
30083263	14	30	theme	transcriptional	1810:1824	arg1	activity					1826:1833	the transcriptional activity	1806:1833	the transcriptional activity of TCF3 transcription factor	1806:1862	Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.
30083263	15	31	theme	Galectin-7	2025:2034	arg1	function					2013:2020	the oncogenic function	1999:2020	the oncogenic function of Galectin-7	1999:2034	Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
30083263	0	32	theme	axis	113:116	arg1	signaling					118:126	Galectin-7-TCF3-MMP9 axis signaling	92:126	Galectin-7-TCF3-MMP9 axis signaling	92:126	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	5	33	theme	patient	580:586	arg1	tissues					588:594	HNSCC patient tissues	574:594	HNSCC patient tissues	574:594	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	12	34	theme	Tid1-deficient	1395:1408	arg1	mice					1410:1413	Keratinocyte-specific Tid1-deficient mice	1373:1413	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment	1373:1460	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	3	35	theme	molecular	349:357	arg1	details					359:365	the molecular details	345:365	the molecular details of Tid1-mediated anti-metastasis	345:398	However, the molecular details of Tid1-mediated anti-metastasis remain elusive.
30083263	4	36	theme	mass	470:473	arg1	spectrometry					475:486	systemic mass spectrometry	461:486	systemic mass spectrometry	461:486	Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins.
30083263	9	37	theme	HNSCC	1143:1147	arg1	patients					1149:1156	HNSCC patients	1143:1156	HNSCC patients	1143:1156	An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients.
30083263	13	38	theme	proteasomal	1652:1662	arg1	degradation					1664:1674	proteasomal degradation	1652:1674	proteasomal degradation	1652:1674	Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7.
30083263	0	39	theme	HSP40	0:4	arg1	Tid1					27:30	HSP40 co-chaperone protein Tid1	0:30	HSP40 co-chaperone protein Tid1	0:30	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	0	40	theme	protein	19:25	arg1	Tid1					27:30	HSP40 co-chaperone protein Tid1	0:30	HSP40 co-chaperone protein Tid1	0:30	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	10	41	theme	high	1172:1175	arg1	expression					1188:1197	high Galectin-7 expression	1172:1197	high Galectin-7 expression	1172:1197	Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC.
30083263	3	42	theme	anti-metastasis	384:398	arg1	details					359:365	the molecular details	345:365	the molecular details of Tid1-mediated anti-metastasis	345:398	However, the molecular details of Tid1-mediated anti-metastasis remain elusive.
30083263	11	43	theme	nuclear	1273:1279	arg1	translocation					1281:1293	the nuclear translocation	1269:1293	the nuclear translocation of Galectin-7	1269:1307	Furthermore, Tid1 abolished the nuclear translocation of Galectin-7 and suppressed Galectin-7-induced tumorigenesis and metastasis.
30083263	11	44	theme	Galectin-7-induced	1324:1341	arg1	tumorigenesis					1343:1355	Galectin-7-induced tumorigenesis	1324:1355	Galectin-7-induced tumorigenesis	1324:1355	Furthermore, Tid1 abolished the nuclear translocation of Galectin-7 and suppressed Galectin-7-induced tumorigenesis and metastasis.
30083263	10	45	theme	poor	1209:1212	arg1	survival					1222:1229	poor overall survival	1209:1229	poor overall survival in HNSCC	1209:1238	Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC.
30083263	15	46	theme	HNSCC	2077:2081	arg1	progression					2083:2093	HNSCC progression	2077:2093	HNSCC progression	2077:2093	Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
30083263	7	47	dep	partner	862:868	arg1	The					846:848	The	846:848	The	846:848	The interacting partner and downstream target of Tid1-interacting client protein were determined.
30083263	1	48	theme	tumor	214:218	arg1	suppressor					220:229	a tumor suppressor	212:229	a tumor suppressor	212:229	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	48	theme	tumor	214:218	arg1	disc					153:156	Human tumorous imaginal disc	129:156	Human tumorous imaginal disc (Tid1)	129:163	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	10	49	from	survival	1222:1229	arg1	HNSCC					1234:1238	HNSCC	1234:1238	HNSCC	1234:1238	Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC.
30083263	8	50	theme	Tid1-interacting	1010:1025	arg1	proteins					1034:1041	the Tid1-interacting client proteins	1006:1041	the Tid1-interacting client proteins	1006:1041	Results: Herein, we first revealed that Galectin-7 was one of the Tid1-interacting client proteins.
30083263	15	51	theme	great	2048:2052	arg1	potential					2054:2062	great potential	2048:2062	great potential	2048:2062	Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
30083263	5	52	theme	client	688:693	arg1	proteins					695:702	Tid1-interacting client proteins	671:702	Tid1-interacting client proteins	671:702	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	8	53	theme	proteins	1034:1041	arg1	proteins					1034:1041	the Tid1-interacting client proteins	1006:1041	the Tid1-interacting client proteins	1006:1041	Results: Herein, we first revealed that Galectin-7 was one of the Tid1-interacting client proteins.
30083263	8	53	theme	proteins	1034:1041	arg1	one					999:1001	one	999:1001	one	999:1001	Results: Herein, we first revealed that Galectin-7 was one of the Tid1-interacting client proteins.
30083263	7	54	theme	client	912:917	arg1	protein					919:925	Tid1-interacting client protein	895:925	Tid1-interacting client protein	895:925	The interacting partner and downstream target of Tid1-interacting client protein were determined.
30083263	12	55	theme	survival	1526:1533	arg1	rate					1535:1538	a poor survival rate	1519:1538	a poor survival rate	1519:1538	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	5	56	theme	expression	649:658	arg1	profile					660:666	the expression profile	645:666	the expression profile of Tid1-interacting client proteins	645:702	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	2	57	theme	squamous	292:299	arg1	carcinoma					306:314	squamous cell carcinoma	292:314	squamous cell carcinoma	292:314	Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy.
30083263	1	58	theme	DnaJ	168:171	arg1	disc					153:156	Human tumorous imaginal disc	129:156	Human tumorous imaginal disc (Tid1)	129:163	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	58	theme	DnaJ	168:171	arg1	protein					186:192	a DnaJ co-chaperone protein	166:192	a DnaJ co-chaperone protein	166:192	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	7	59	theme	downstream	874:883	arg1	target					885:890	downstream target	874:890	downstream target	874:890	The interacting partner and downstream target of Tid1-interacting client protein were determined.
30083263	9	60	theme	inverse	1047:1053	arg1	association					1055:1065	An inverse association	1044:1065	An inverse association of protein expression profile between Tid1 and Galectin-7	1044:1123	An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients.
30083263	5	61	theme	Tid1	566:569	arg1	staining					554:561	Immunohistochemical staining	534:561	Immunohistochemical staining of Tid1 in HNSCC patient tissues	534:594	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	13	62	link	N-linked	1585:1592	arg1	glycosylation					1594:1606	its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7	1581:1688	its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7	1581:1688	Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7.
30083263	12	63	theme	protein	1482:1488	arg1	levels					1490:1495	increased protein levels	1472:1495	increased protein levels of Galectin-7	1472:1509	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	12	64	with	mice	1410:1413	arg1	treatment					1452:1460	4-nitroquinoline-1-oxide (4NQO) treatment	1420:1460	4-nitroquinoline-1-oxide (4NQO) treatment	1420:1460	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	2	65	dep	head	278:281	arg1	carcinoma					306:314	squamous cell carcinoma	292:314	squamous cell carcinoma	292:314	Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy.
30083263	15	66	theme	Tid1	1959:1962	arg1	expression					1964:1973	Tid1 expression	1959:1973	Tid1 expression	1959:1973	Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
30083263	5	67	theme	HNSCC	574:578	arg1	tissues					588:594	HNSCC patient tissues	574:594	HNSCC patient tissues	574:594	Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.
30083263	1	68	theme	tumorous	135:142	arg1	suppressor					220:229	a tumor suppressor	212:229	a tumor suppressor	212:229	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	68	theme	tumorous	135:142	arg1	Tid1					159:162	Tid1	159:162	Tid1	159:162	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	68	theme	tumorous	135:142	arg1	protein					186:192	a DnaJ co-chaperone protein	166:192	a DnaJ co-chaperone protein	166:192	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	1	68	theme	tumorous	135:142	arg1	disc					153:156	Human tumorous imaginal disc	129:156	Human tumorous imaginal disc (Tid1)	129:163	Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.
30083263	9	69	theme	expression	1078:1087	arg1	profile					1089:1095	protein expression profile	1070:1095	protein expression profile	1070:1095	An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients.
30083263	0	70	theme	neck	66:69	arg1	metastasis					43:52	metastasis	43:52	metastasis of head and neck cancer	43:76	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	14	71	theme	factor	1857:1862	arg1	activity					1826:1833	the transcriptional activity	1806:1833	the transcriptional activity of TCF3 transcription factor	1806:1862	Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.
30083263	14	72	theme	TCF3	1838:1841	arg1	factor					1857:1862	TCF3 transcription factor	1838:1862	TCF3 transcription factor	1838:1862	Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.
30083263	4	73	theme	client	517:522	arg1	proteins					524:531	Tid1-interacting client proteins	500:531	Tid1-interacting client proteins	500:531	Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins.
30083263	15	74	theme	Overall	1913:1919	arg1	treatments					1929:1938	Overall, future treatments	1913:1938	Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7	1913:2034	Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
30083263	0	75	theme	Galectin-7-TCF3-MMP9	92:111	arg1	signaling					118:126	Galectin-7-TCF3-MMP9 axis signaling	92:126	Galectin-7-TCF3-MMP9 axis signaling	92:126	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	4	76	theme	systemic	461:468	arg1	spectrometry					475:486	systemic mass spectrometry	461:486	systemic mass spectrometry	461:486	Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins.
30083263	13	77	theme	N-linked	1585:1592	arg1	glycosylation					1594:1606	its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7	1581:1688	its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7	1581:1688	Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7.
30083263	10	78	theme	Low	1159:1161	arg1	Tid1					1163:1166	Low Tid1	1159:1166	Low Tid1	1159:1166	Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC.
30083263	15	79	theme	oncogenic	2003:2011	arg1	function					2013:2020	the oncogenic function	1999:2020	the oncogenic function of Galectin-7	1999:2034	Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
30083263	0	80	theme	co-chaperone	6:17	arg1	Tid1					27:30	HSP40 co-chaperone protein Tid1	0:30	HSP40 co-chaperone protein Tid1	0:30	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	12	81	theme	4-nitroquinoline-1-oxide	1420:1443	arg1	treatment					1452:1460	4-nitroquinoline-1-oxide (4NQO) treatment	1420:1460	4-nitroquinoline-1-oxide (4NQO) treatment	1420:1460	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	10	82	theme	Galectin-7	1177:1186	arg1	expression					1188:1197	high Galectin-7 expression	1172:1197	high Galectin-7 expression	1172:1197	Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC.
30083263	6	83	theme	client	774:779	arg1	proteins					781:788	Tid1-interacting client proteins	757:788	Tid1-interacting client proteins	757:788	The roles of Tid1-interacting client proteins in metastasis were validated both in vitro and in vivo.
30083263	11	84	theme	Galectin-7	1298:1307	arg1	translocation					1281:1293	the nuclear translocation	1269:1293	the nuclear translocation of Galectin-7	1269:1307	Furthermore, Tid1 abolished the nuclear translocation of Galectin-7 and suppressed Galectin-7-induced tumorigenesis and metastasis.
30083263	0	85	dep	head	57:60	arg1	cancer					71:76	cancer	71:76	cancer	71:76	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	12	86	theme	Keratinocyte-specific	1373:1393	arg1	mice					1410:1413	Keratinocyte-specific Tid1-deficient mice	1373:1413	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment	1373:1460	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	13	87	theme	Tid1-mediated	1619:1631	arg1	ubiquitination					1633:1646	Tid1-mediated ubiquitination	1619:1646	Tid1-mediated ubiquitination	1619:1646	Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7.
30083263	0	88	theme	head	57:60	arg1	metastasis					43:52	metastasis	43:52	metastasis of head and neck cancer	43:76	HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.
30083263	10	89	theme	overall	1214:1220	arg1	survival					1222:1229	poor overall survival	1209:1229	poor overall survival in HNSCC	1209:1238	Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC.
30083263	3	90	theme	Tid1-mediated	370:382	arg1	anti-metastasis					384:398	Tid1-mediated anti-metastasis	370:398	Tid1-mediated anti-metastasis	370:398	However, the molecular details of Tid1-mediated anti-metastasis remain elusive.
30083263	15	91	dep	Overall	1913:1919	arg1	future					1922:1927	future	1922:1927	future	1922:1927	Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
30083263	6	92	theme	proteins	781:788	arg1	roles					748:752	The roles	744:752	The roles of Tid1-interacting client proteins in metastasis	744:802	The roles of Tid1-interacting client proteins in metastasis were validated both in vitro and in vivo.
30083263	2	93	theme	cell	301:304	arg1	carcinoma					306:314	squamous cell carcinoma	292:314	squamous cell carcinoma	292:314	Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy.
30083263	12	94	contain	had	1515:1517	arg2	rate					1535:1538	a poor survival rate	1519:1538	a poor survival rate	1519:1538	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	12	94	contain	had	1515:1517	arg1	mice					1410:1413	Keratinocyte-specific Tid1-deficient mice	1373:1413	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment	1373:1460	Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.
30083263	6	95	theme	Tid1-interacting	757:772	arg1	proteins					781:788	Tid1-interacting client proteins	757:788	Tid1-interacting client proteins	757:788	The roles of Tid1-interacting client proteins in metastasis were validated both in vitro and in vivo.
29350927	5	0	theme	8p	1105:1106	arg1	Crystallization					1086:1100	Crystallization	1086:1100	Crystallization of 8p with the amino terminal domain of hmGlu3	1086:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	1	1	theme	3-methoxybenzoyl	172:187	arg1	S					157:157	S	157:157	S	157:157	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	1	theme	3-methoxybenzoyl	172:187	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	1	theme	3-methoxybenzoyl	172:187	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	1	theme	3-methoxybenzoyl	172:187	arg1	LY2794193					239:247	LY2794193	239:247	LY2794193	239:247	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	3	2	link	C4β-N-linked	643:654	arg1	variants					656:663	C4β-N-linked variants	643:663	C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	643:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	1	3	theme	Potent	260:265	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	3	theme	Potent	260:265	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	3	4	theme	R,6	679:681	arg1	S					683:683	1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0	669:706	(1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	668:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	4	5	theme	-2-amino-4-[	923:934	arg1	acid					997:1000	-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p	923:1003	(1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193)	902:1015	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	5	theme	-2-amino-4-[	923:934	arg1	LY2794193					1006:1014	LY2794193	1006:1014	LY2794193	1006:1014	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	5	theme	-2-amino-4-[	923:934	arg1	molecule					1020:1027	a molecule	1018:1027	a molecule that demonstrates remarkable mGlu3 receptor selectivity	1018:1083	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	5	theme	-2-amino-4-[	923:934	arg1	S					921:921	S	921:921	S	921:921	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	3	6	theme	S	683:683	arg1	acid					732:735	(1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1	668:737	(1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	668:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	6	theme	S	683:683	arg1	LY354740					740:747	LY354740	740:747	LY354740	740:747	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	2	7	theme	Multiple	305:312	arg1	opportunities					326:338	Multiple therapeutic opportunities	305:338	Multiple therapeutic opportunities	305:338	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	3	8	theme	bioavailable	570:581	arg1	agonists					583:590	potent, selective, and systemically bioavailable agonists	534:590	potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes	534:628	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	1	9	theme	Selective	271:279	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	9	theme	Selective	271:279	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	3	10	theme	acid	732:735	arg1	variants					656:663	C4β-N-linked variants	643:663	C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	643:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	2	11	theme	selective	385:393	arg1	activation					395:404	selective activation	385:404	selective activation of metabotropic glutamate 3 (mGlu3) receptors	385:450	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	1	12	theme	mGlu3	281:285	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	12	theme	mGlu3	281:285	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	4	13	theme	3-methoxybenzoyl	936:951	arg1	acid					997:1000	-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p	923:1003	(1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193)	902:1015	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	13	theme	3-methoxybenzoyl	936:951	arg1	LY2794193					1006:1014	LY2794193	1006:1014	LY2794193	1006:1014	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	13	theme	3-methoxybenzoyl	936:951	arg1	molecule					1020:1027	a molecule	1018:1027	a molecule that demonstrates remarkable mGlu3 receptor selectivity	1018:1083	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	13	theme	3-methoxybenzoyl	936:951	arg1	S					921:921	S	921:921	S	921:921	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	2	14	theme	receptors	442:450	arg1	activation					395:404	selective activation	385:404	selective activation of metabotropic glutamate 3 (mGlu3) receptors	385:450	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	1	15	theme	bicyclo[3.1.0	195:207	arg1	S					157:157	S	157:157	S	157:157	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	15	theme	bicyclo[3.1.0	195:207	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	15	theme	bicyclo[3.1.0	195:207	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	15	theme	bicyclo[3.1.0	195:207	arg1	LY2794193					239:247	LY2794193	239:247	LY2794193	239:247	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	16	theme	amino	189:193	arg1	S					157:157	S	157:157	S	157:157	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	16	theme	amino	189:193	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	16	theme	amino	189:193	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	16	theme	amino	189:193	arg1	LY2794193					239:247	LY2794193	239:247	LY2794193	239:247	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	3	17	theme	binding	812:818	arg1	affinity					820:827	mGlu3 receptor binding affinity	797:827	mGlu3 receptor binding affinity	797:827	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	4	18	theme	hexane-2,6-dicarboxylic	973:995	arg1	acid					997:1000	-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p	923:1003	(1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193)	902:1015	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	18	theme	hexane-2,6-dicarboxylic	973:995	arg1	LY2794193					1006:1014	LY2794193	1006:1014	LY2794193	1006:1014	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	18	theme	hexane-2,6-dicarboxylic	973:995	arg1	molecule					1020:1027	a molecule	1018:1027	a molecule that demonstrates remarkable mGlu3 receptor selectivity	1018:1083	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	18	theme	hexane-2,6-dicarboxylic	973:995	arg1	S					921:921	S	921:921	S	921:921	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	5	19	theme	compound	1407:1414	arg1	doses					1393:1397	doses	1393:1397	doses of this compound	1393:1414	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	3	20	theme	selective	542:550	arg1	agonists					583:590	potent, selective, and systemically bioavailable agonists	534:590	potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes	534:628	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	5	21	theme	mGlu2	1328:1332	arg1	model					1364:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	3	22	theme	hexane-2,6-dicarboxylic	708:730	arg1	acid					732:735	(1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1	668:737	(1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	668:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	22	theme	hexane-2,6-dicarboxylic	708:730	arg1	LY354740					740:747	LY354740	740:747	LY354740	740:747	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	5	23	theme	central	1474:1480	arg1	receptors					1488:1496	central mGlu3 receptors	1474:1496	central mGlu3 receptors	1474:1496	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	24	theme	critical	1158:1165	arg1	interactions					1175:1186	critical binding interactions	1158:1186	critical binding interactions for this ligand with residues adjacent to the glutamate binding site	1158:1255	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	25	theme	8p	1294:1295	arg1	assessment					1280:1289	pharmacokinetic assessment	1264:1289	pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model	1264:1368	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	26	theme	receptor-dependent	1334:1351	arg1	model					1364:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	2	27	theme	glutamate	422:430	arg1	receptors					442:450	metabotropic glutamate 3 (mGlu3) receptors	409:450	metabotropic glutamate 3 (mGlu3) receptors	409:450	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	2	28	theme	molecule	463:470	arg1	tools					472:476	small molecule tools	457:476	small molecule tools	457:476	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	1	29	theme	Receptor	287:294	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	29	theme	Receptor	287:294	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	5	30	theme	mGlu3	1482:1486	arg1	receptors					1488:1496	central mGlu3 receptors	1474:1496	central mGlu3 receptors	1474:1496	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	31	theme	amino	1117:1121	arg1	hmGlu3					1142:1147	hmGlu3	1142:1147	hmGlu3	1142:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	31	theme	amino	1117:1121	arg1	domain					1132:1137	the amino terminal domain	1113:1137	the amino terminal domain of hmGlu3	1113:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	2	32	theme	metabotropic	409:420	arg1	receptors					442:450	metabotropic glutamate 3 (mGlu3) receptors	409:450	metabotropic glutamate 3 (mGlu3) receptors	409:450	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	2	33	theme	small	457:461	arg1	tools					472:476	small molecule tools	457:476	small molecule tools	457:476	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	5	34	theme	binding	1167:1173	arg1	interactions					1175:1186	critical binding interactions	1158:1186	critical binding interactions for this ligand with residues adjacent to the glutamate binding site	1158:1255	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	35	with	Crystallization	1086:1100	arg1	hmGlu3					1142:1147	hmGlu3	1142:1147	hmGlu3	1142:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	35	with	Crystallization	1086:1100	arg1	domain					1132:1137	the amino terminal domain	1113:1137	the amino terminal domain of hmGlu3	1113:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	3	36	theme	receptor	803:810	arg1	affinity					820:827	mGlu3 receptor binding affinity	797:827	mGlu3 receptor binding affinity	797:827	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	1	37	theme	hexane-2,6-dicarboxylic	209:231	arg1	S					157:157	S	157:157	S	157:157	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	37	theme	hexane-2,6-dicarboxylic	209:231	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	37	theme	hexane-2,6-dicarboxylic	209:231	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	37	theme	hexane-2,6-dicarboxylic	209:231	arg1	LY2794193					239:247	LY2794193	239:247	LY2794193	239:247	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	0	38	theme	Pharmacological	14:28	arg1	Characterization					30:45	Pharmacological Characterization	14:45	Pharmacological Characterization	14:45	Synthesis and Pharmacological Characterization of C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates.
29350927	3	39	theme	variants	656:663	arg1	part					494:497	part	494:497	part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes	494:628	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	39	theme	variants	656:663	arg1	series					633:638	a series	631:638	a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	631:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	2	40	theme	therapeutic	314:324	arg1	opportunities					326:338	Multiple therapeutic opportunities	305:338	Multiple therapeutic opportunities	305:338	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	1	41	theme	Acid	233:236	arg1	Identification					120:133	Identification	120:133	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.	120:303	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	0	42	theme	C4β-Amide-Substituted	50:70	arg1	hexane-2,6-dicarboxylates					93:117	C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates	50:117	C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates	50:117	Synthesis and Pharmacological Characterization of C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates.
29350927	3	43	theme	mGlu3	606:610	arg1	subtypes					621:628	mGlu3 receptor subtypes	606:628	mGlu3 receptor subtypes	606:628	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	4	44	theme	receptor	1064:1071	arg1	selectivity					1073:1083	remarkable mGlu3 receptor selectivity	1047:1083	remarkable mGlu3 receptor selectivity	1047:1083	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	5	45	theme	pharmacokinetic	1264:1278	arg1	assessment					1280:1289	pharmacokinetic assessment	1264:1289	pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model	1264:1368	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	3	46	theme	receptor	612:619	arg1	subtypes					621:628	mGlu3 receptor subtypes	606:628	mGlu3 receptor subtypes	606:628	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	2	47	theme	mGlu3	435:439	arg1	receptors					442:450	metabotropic glutamate 3 (mGlu3) receptors	409:450	metabotropic glutamate 3 (mGlu3) receptors	409:450	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	3	48	theme	efforts	514:520	arg1	part					494:497	part	494:497	part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes	494:628	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	48	theme	efforts	514:520	arg1	series					633:638	a series	631:638	a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	631:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	49	theme	C4β-N-linked	643:654	arg1	variants					656:663	C4β-N-linked variants	643:663	C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	643:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	2	50	theme	capable	374:380	arg1	compounds					364:372	compounds	364:372	compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors	364:450	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	0	51	theme	2-Aminobicyclo[3.1.0	72:91	arg1	hexane-2,6-dicarboxylates					93:117	C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates	50:117	C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates	50:117	Synthesis and Pharmacological Characterization of C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates.
29350927	5	52	theme	hmGlu3	1142:1147	arg1	hmGlu3					1142:1147	hmGlu3	1142:1147	hmGlu3	1142:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	52	theme	hmGlu3	1142:1147	arg1	domain					1132:1137	the amino terminal domain	1113:1137	the amino terminal domain of hmGlu3	1113:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	3	53	theme	S,2	671:673	arg1	S					683:683	1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0	669:706	(1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	668:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	54	theme	ongoing	506:512	arg1	efforts					514:520	our ongoing efforts	502:520	our ongoing efforts	502:520	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	4	55	theme	mGlu3	1058:1062	arg1	selectivity					1073:1083	remarkable mGlu3 receptor selectivity	1047:1083	remarkable mGlu3 receptor selectivity	1047:1083	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	3	56	theme	S,5	675:677	arg1	S					683:683	1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0	669:706	(1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740)	668:748	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	5	57	from	effect	1315:1320	arg1	model					1364:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	4	58	theme	remarkable	1047:1056	arg1	selectivity					1073:1083	remarkable mGlu3 receptor selectivity	1047:1083	remarkable mGlu3 receptor selectivity	1047:1083	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	5	59	theme	adjacent	1218:1225	arg1	residues					1209:1216	residues	1209:1216	residues adjacent to the glutamate binding site	1209:1255	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	60	theme	behavioral	1353:1362	arg1	model					1364:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	an mGlu2 receptor-dependent behavioral model	1325:1368	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	3	61	theme	potent	534:539	arg1	agonists					583:590	potent, selective, and systemically bioavailable agonists	534:590	potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes	534:628	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	62	theme	functional	833:842	arg1	responses					853:861	functional cellular responses	833:861	functional cellular responses	833:861	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	3	63	theme	mGlu3	797:801	arg1	affinity					820:827	mGlu3 receptor binding affinity	797:827	mGlu3 receptor binding affinity	797:827	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	4	64	theme	amino	953:957	arg1	acid					997:1000	-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p	923:1003	(1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193)	902:1015	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	64	theme	amino	953:957	arg1	LY2794193					1006:1014	LY2794193	1006:1014	LY2794193	1006:1014	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	64	theme	amino	953:957	arg1	molecule					1020:1027	a molecule	1018:1027	a molecule that demonstrates remarkable mGlu3 receptor selectivity	1018:1083	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	4	64	theme	amino	953:957	arg1	S					921:921	S	921:921	S	921:921	From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
29350927	5	65	theme	terminal	1123:1130	arg1	hmGlu3					1142:1147	hmGlu3	1142:1147	hmGlu3	1142:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	65	theme	terminal	1123:1130	arg1	domain					1132:1137	the amino terminal domain	1113:1137	the amino terminal domain of hmGlu3	1113:1147	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	1	66	theme	-2-Amino-4-[	159:170	arg1	S					157:157	S	157:157	S	157:157	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	66	theme	-2-Amino-4-[	159:170	arg1	Acid					233:236	-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid	159:236	(1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193)	138:248	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	66	theme	-2-Amino-4-[	159:170	arg1	Agonist					296:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	a Highly Potent and Selective mGlu3 Receptor Agonist	251:302	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	1	66	theme	-2-Amino-4-[	159:170	arg1	LY2794193					239:247	LY2794193	239:247	LY2794193	239:247	Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
29350927	3	67	theme	cellular	844:851	arg1	responses					853:861	functional cellular responses	833:861	functional cellular responses	833:861	As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor subtypes, a series of C4β-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional cellular responses.
29350927	0	68	theme	hexane-2,6-dicarboxylates	93:117	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis	0:8	Synthesis and Pharmacological Characterization of C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates.
29350927	0	68	theme	hexane-2,6-dicarboxylates	93:117	arg1	Characterization					30:45	Pharmacological Characterization	14:45	Pharmacological Characterization	14:45	Synthesis and Pharmacological Characterization of C4β-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates.
29350927	5	69	with	interactions	1175:1186	arg1	residues					1209:1216	residues	1209:1216	residues adjacent to the glutamate binding site	1209:1255	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	2	70	theme	activation	395:404	arg1	capable					374:380	capable	374:380	capable	374:380	Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking.
29350927	5	71	theme	binding	1244:1250	arg1	site					1252:1255	the glutamate binding site	1230:1255	the glutamate binding site	1230:1255	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
29350927	5	72	theme	glutamate	1234:1242	arg1	site					1252:1255	the glutamate binding site	1230:1255	the glutamate binding site	1230:1255	Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical binding interactions for this ligand with residues adjacent to the glutamate binding site, while pharmacokinetic assessment of 8p combined with its effect in an mGlu2 receptor-dependent behavioral model provides estimates for doses of this compound that would be expected to selectively engage and activate central mGlu3 receptors in vivo.
30076101	4	0	contain	containing	793:802	arg2	segment					844:850	the germline VRC01 VH segment	822:850	the germline VRC01 VH segment	822:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	0	contain	containing	793:802	arg1	chains					786:791	diverse immunoglobulin heavy chains	757:791	diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment	757:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	0	contain	containing	793:802	arg2	IGHV1-2∗02					810:819	human IGHV1-2∗02	804:819	human IGHV1-2∗02	804:819	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	1	1	theme	HIV-1	154:158	arg1	antibodies					181:190	HIV-1 broadly neutralizing antibodies	154:190	HIV-1 broadly neutralizing antibodies	154:190	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	2	2	theme	domain	324:329	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	2	theme	domain	324:329	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	5	3	theme	higher	945:950	arg1	precursors					1065:1074	VRC01-class precursors	1053:1074	VRC01-class precursors	1053:1074	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	5	3	theme	higher	945:950	arg1	proportions					952:962	significantly higher proportions	931:962	significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors	931:1074	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	5	4	theme	cells	1037:1041	arg1	precursors					1065:1074	VRC01-class precursors	1053:1074	VRC01-class precursors	1053:1074	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	5	4	theme	cells	1037:1041	arg1	proportions					952:962	significantly higher proportions	931:962	significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors	931:1074	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	5	5	theme	G+	1032:1033	arg1	cells					1037:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	4	6	theme	diverse	757:763	arg1	chains					786:791	diverse immunoglobulin heavy chains	757:791	diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment	757:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	7	theme	mouse	730:734	arg1	model					736:740	a mouse model	728:740	a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment	728:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	5	8	theme	responses	988:996	arg1	precursors					1065:1074	VRC01-class precursors	1053:1074	VRC01-class precursors	1053:1074	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	5	8	theme	responses	988:996	arg1	proportions					952:962	significantly higher proportions	931:962	significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors	931:1074	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	6	9	theme	design	1243:1248	arg1	target					1219:1224	a major target	1211:1224	a major target of HIV-1 vaccine design	1211:1248	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	3	10	theme	eOD-GT8-elicited	513:528	arg1	antibodies					530:539	eOD-GT8-elicited antibodies	513:539	eOD-GT8-elicited antibodies	513:539	However, a substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy.
30076101	5	11	with	mutant	889:894	arg1	glycans					912:918	five added glycans	901:918	five added glycans	901:918	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	0	12	theme	Precursor	110:118	arg1	Antibodies					120:129	VRC01-Class Precursor Antibodies	98:129	VRC01-Class Precursor Antibodies	98:129	Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.
30076101	5	13	theme	added	906:910	arg1	glycans					912:918	five added glycans	901:918	five added glycans	901:918	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	4	14	theme	N-linked	617:624	arg1	glycans					626:632	N-linked glycans	617:632	N-linked glycans	617:632	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	3	15	theme	substantial	490:500	arg1	portion					502:508	a substantial portion	488:508	a substantial portion of eOD-GT8-elicited antibodies	488:539	However, a substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy.
30076101	1	16	theme	neutralizing	168:179	arg1	antibodies					181:190	HIV-1 broadly neutralizing antibodies	154:190	HIV-1 broadly neutralizing antibodies	154:190	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	0	17	theme	VRC01-Class	98:108	arg1	Antibodies					120:129	VRC01-Class Precursor Antibodies	98:129	VRC01-Class Precursor Antibodies	98:129	Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.
30076101	4	18	theme	immunoglobulin	765:778	arg1	chains					786:791	diverse immunoglobulin heavy chains	757:791	diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment	757:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	1	19	theme	antibodies	181:190	arg1	class					145:149	An important class	132:149	An important class	132:149	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	3	20	theme	non-CD4bs	548:556	arg1	epitopes					558:565	non-CD4bs epitopes	548:565	non-CD4bs epitopes	548:565	However, a substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy.
30076101	2	21	theme	60-mer	344:349	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	21	theme	60-mer	344:349	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	0	22	theme	Glycan	0:5	arg1	Masking					7:13	Glycan Masking	0:13	Glycan Masking	0:13	Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.
30076101	5	23	theme	CD4bs-specific	1002:1015	arg1	cells					1037:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	2	24	theme	eOD-GT8	336:342	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	24	theme	eOD-GT8	336:342	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	0	25	theme	Immune	23:28	arg1	Responses					30:38	Immune Responses	23:38	Immune Responses to the HIV-1 CD4-Binding Site	23:68	Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.
30076101	6	26	theme	vaccine	1235:1241	arg1	design					1243:1248	HIV-1 vaccine design	1229:1248	HIV-1 vaccine design	1229:1248	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	3	27	theme	antibodies	530:539	arg1	portion					502:508	a substantial portion	488:508	a substantial portion of eOD-GT8-elicited antibodies	488:539	However, a substantial portion of eOD-GT8-elicited antibodies target non-CD4bs epitopes, potentially limiting its efficacy.
30076101	2	28	theme	priming	388:394	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	28	theme	priming	388:394	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	1	29	theme	envelope	271:278	arg1	Env					294:296	Env	294:296	Env	294:296	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	29	theme	envelope	271:278	arg1	glycoprotein					280:291	the envelope glycoprotein	267:291	the envelope glycoprotein (Env)	267:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	0	30	theme	Antibodies	120:129	arg1	Elicitation					83:93	Elicitation	83:93	Elicitation of VRC01-Class Precursor Antibodies	83:129	Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.
30076101	6	31	theme	HIV-1	1229:1233	arg1	design					1243:1248	HIV-1 vaccine design	1229:1248	HIV-1 vaccine design	1229:1248	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	5	32	theme	CD4bs-specific	967:980	arg1	responses					988:996	CD4bs-specific serum responses	967:996	CD4bs-specific serum responses	967:996	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	1	33	theme	VRC01	204:208	arg1	class					210:214	the VRC01 class	200:214	the VRC01 class	200:214	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	34	theme	glycoprotein	280:291	arg1	glycoprotein					280:291	the envelope glycoprotein	267:291	the envelope glycoprotein (Env)	267:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	34	theme	glycoprotein	280:291	arg1	CD4bs					257:261	CD4bs	257:261	CD4bs	257:261	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	34	theme	glycoprotein	280:291	arg1	site					251:254	the conserved CD4-binding site	225:254	the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env)	225:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	6	35	theme	immune	1180:1185	arg1	responses					1187:1195	immune responses	1180:1195	immune responses to the CD4bs	1180:1208	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	4	36	theme	the germline	822:833	arg1	segment					844:850	the germline VRC01 VH segment	822:850	the germline VRC01 VH segment	822:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	36	theme	the germline	822:833	arg1	IGHV1-2∗02					810:819	human IGHV1-2∗02	804:819	human IGHV1-2∗02	804:819	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	37	theme	eOD-GT8	661:667	arg1	surfaces					649:656	non-CD4bs surfaces	639:656	non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes	639:695	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	38	theme	non-CD4bs	639:647	arg1	surfaces					649:656	non-CD4bs surfaces	639:656	non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes	639:695	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	5	39	theme	VRC01-class	1053:1063	arg1	precursors					1065:1074	VRC01-class precursors	1053:1074	VRC01-class precursors	1053:1074	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	0	40	theme	HIV-1	47:51	arg1	Site					65:68	the HIV-1 CD4-Binding Site	43:68	the HIV-1 CD4-Binding Site	43:68	Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.
30076101	2	41	theme	clinical	462:469	arg1	trials					471:476	clinical trials	462:476	clinical trials	462:476	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	4	42	theme	VH	841:842	arg1	segment					844:850	the germline VRC01 VH segment	822:850	the germline VRC01 VH segment	822:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	42	theme	VH	841:842	arg1	IGHV1-2∗02					810:819	human IGHV1-2∗02	804:819	human IGHV1-2∗02	804:819	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	6	43	theme	antibodies	1159:1168	arg1	elicitation					1133:1143	elicitation	1133:1143	elicitation of off-target antibodies	1133:1168	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	2	44	theme	outer	318:322	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	44	theme	outer	318:322	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	45	theme	VRC01-class	420:430	arg1	precursors					432:441	VRC01-class precursors	420:441	VRC01-class precursors	420:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	6	46	theme	glycan	1108:1113	arg1	masking					1115:1121	glycan masking	1108:1121	glycan masking	1108:1121	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	4	47	theme	VRC01	835:839	arg1	segment					844:850	the germline VRC01 VH segment	822:850	the germline VRC01 VH segment	822:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	47	theme	VRC01	835:839	arg1	IGHV1-2∗02					810:819	human IGHV1-2∗02	804:819	human IGHV1-2∗02	804:819	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	1	48	gly	glycoprotein	280:291	arg1	Env					294:296	Env	294:296	Env	294:296	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	48	gly	glycoprotein	280:291	arg1	glycoprotein					280:291	the envelope glycoprotein	267:291	the envelope glycoprotein (Env)	267:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	2	49	theme	Env	314:316	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	49	theme	Env	314:316	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	4	50	theme	human	804:808	arg1	segment					844:850	the germline VRC01 VH segment	822:850	the germline VRC01 VH segment	822:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	4	50	theme	human	804:808	arg1	IGHV1-2∗02					810:819	human IGHV1-2∗02	804:819	human IGHV1-2∗02	804:819	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	6	51	theme	major	1213:1217	arg1	target					1219:1224	a major target	1211:1224	a major target of HIV-1 vaccine design	1211:1248	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	5	52	theme	immunoglobulin	1017:1030	arg1	cells					1037:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	4	53	theme	mask	672:675	arg1	epitopes					688:695	mask irrelevant epitopes	672:695	mask irrelevant epitopes	672:695	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	2	54	theme	engineered	303:312	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	54	theme	engineered	303:312	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	4	55	theme	heavy	780:784	arg1	chains					786:791	diverse immunoglobulin heavy chains	757:791	diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment	757:850	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	5	56	theme	serum	982:986	arg1	responses					988:996	CD4bs-specific serum responses	967:996	CD4bs-specific serum responses	967:996	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	1	57	theme	important	135:143	arg1	class					145:149	An important class	132:149	An important class	132:149	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	6	58	theme	off-target	1148:1157	arg1	antibodies					1159:1168	off-target antibodies	1148:1168	off-target antibodies	1148:1168	These results demonstrate that glycan masking can limit elicitation of off-target antibodies and focus immune responses to the CD4bs, a major target of HIV-1 vaccine design.
30076101	5	59	theme	B	1035:1035	arg1	cells					1037:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	CD4bs-specific immunoglobulin G+ B cells	1002:1041	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	4	60	theme	irrelevant	677:686	arg1	epitopes					688:695	mask irrelevant epitopes	672:695	mask irrelevant epitopes	672:695	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	5	61	theme	parental	869:876	arg1	eOD-GT8					878:884	the parental eOD-GT8	865:884	the parental eOD-GT8	865:884	Compared to the parental eOD-GT8, a mutant with five added glycans stimulated significantly higher proportions of CD4bs-specific serum responses and CD4bs-specific immunoglobulin G+ B cells including VRC01-class precursors.
30076101	1	62	theme	conserved	229:237	arg1	glycoprotein					280:291	the envelope glycoprotein	267:291	the envelope glycoprotein (Env)	267:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	62	theme	conserved	229:237	arg1	CD4bs					257:261	CD4bs	257:261	CD4bs	257:261	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	62	theme	conserved	229:237	arg1	site					251:254	the conserved CD4-binding site	225:254	the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env)	225:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	0	63	theme	CD4-Binding	53:63	arg1	Site					65:68	the HIV-1 CD4-Binding Site	43:68	the HIV-1 CD4-Binding Site	43:68	Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies.
30076101	4	64	link	N-linked	617:624	arg1	glycans					626:632	N-linked glycans	617:632	N-linked glycans	617:632	We introduced N-linked glycans into non-CD4bs surfaces of eOD-GT8 to mask irrelevant epitopes and evaluated these mutants in a mouse model that expressed diverse immunoglobulin heavy chains containing human IGHV1-2∗02, the germline VRC01 VH segment.
30076101	2	65	theme	OD	332:333	arg1	nanoparticle					351:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle	300:362	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	2	65	theme	OD	332:333	arg1	immunogen					396:404	a priming immunogen	386:404	a priming immunogen for eliciting VRC01-class precursors	386:441	An engineered Env outer domain (OD) eOD-GT8 60-mer nanoparticle has been developed as a priming immunogen for eliciting VRC01-class precursors and is planned for clinical trials.
30076101	1	66	theme	CD4-binding	239:249	arg1	glycoprotein					280:291	the envelope glycoprotein	267:291	the envelope glycoprotein (Env)	267:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	66	theme	CD4-binding	239:249	arg1	CD4bs					257:261	CD4bs	257:261	CD4bs	257:261	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
30076101	1	66	theme	CD4-binding	239:249	arg1	site					251:254	the conserved CD4-binding site	225:254	the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env)	225:297	An important class of HIV-1 broadly neutralizing antibodies, termed the VRC01 class, targets the conserved CD4-binding site (CD4bs) of the envelope glycoprotein (Env).
28679762	4	0	theme	kDa	827:829	arg1	mass					815:818	a molecular mass	803:818	a molecular mass of 150 kDa	803:829	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	0	1	contain	Have	39:42	arg1	Serotypes					29:37	Adeno-associated Virus (AAV) Serotypes	0:37	Adeno-associated Virus (AAV) Serotypes	0:37	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	0	1	contain	Have	39:42	arg2	Interactions					56:67	Distinctive Interactions	44:67	Distinctive Interactions with Domains of the Cellular AAV Receptor	44:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	7	2	theme	present	1445:1451	arg1	PKD2					1439:1442	PKD2	1439:1442	PKD2	1439:1442	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	2	theme	present	1445:1451	arg1	domain					1431:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain	1373:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	15	3	theme	AAV-AAVR	2552:2559	arg1	interface					2561:2569	the AAV-AAVR interface	2548:2569	the AAV-AAVR interface in more detail	2548:2584	Defining the AAV-AAVR interface in more detail is important to understand how AAV engages with its cellular receptor and how the receptor facilitates the entry process.
28679762	10	4	theme	therapeutic	2007:2017	arg1	applications					2019:2030	therapeutic applications	2007:2030	therapeutic applications	2007:2030	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	8	5	theme	AAVR	1580:1583	arg1	domain					1563:1568	PKD domain	1559:1568	PKD domain (PKD1)	1559:1575	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	5	theme	AAVR	1580:1583	arg1	PKD1					1571:1574	PKD1	1571:1574	PKD1	1571:1574	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	5	theme	AAVR	1580:1583	arg1	AAVR					1580:1583	AAVR	1580:1583	AAVR	1580:1583	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	10	6	theme	distinctive	1866:1876	arg1	interactions					1878:1889	distinctive interactions	1866:1889	distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research	1866:2054	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	7	7	with	complementation	1222:1236	arg1	assays					1281:1286	virus overlay assays	1267:1286	virus overlay assays with individual domains	1267:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	7	with	complementation	1222:1236	arg1	constructs					1252:1261	deletion constructs	1243:1261	deletion constructs	1243:1261	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	8	attach	present	1445:1451	arg1	AAVR					1474:1477	AAVR	1474:1477	AAVR	1474:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	8	attach	present	1445:1451	arg1	ectodomain					1460:1469	the ectodomain	1456:1469	the ectodomain of AAVR	1456:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	8	attach	present	1445:1451	arg2	PKD2					1439:1442	PKD2	1439:1442	PKD2	1439:1442	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	8	attach	present	1445:1451	arg2	domain					1431:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain	1373:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	4	9	theme	molecular	805:813	arg1	mass					815:818	a molecular mass	803:818	a molecular mass of 150 kDa	803:829	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	6	10	theme	strict	1127:1132	arg1	requirement					1134:1144	a strict requirement	1125:1144	a strict requirement for AAV2 binding or functional transduction	1125:1188	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	6	10	theme	strict	1127:1132	arg1	glycosylation					1104:1116	this glycosylation	1099:1116	this glycosylation	1099:1116	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	16	11	with	interactions	2838:2849	arg1	AAVR					2883:2886	AAVR	2883:2886	AAVR	2883:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	16	11	with	interactions	2838:2849	arg1	domains					2872:2878	the Ig-like PKD domains	2856:2878	the Ig-like PKD domains of AAVR	2856:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	15	12	theme	entry	2693:2697	arg1	process					2699:2705	the entry process	2689:2705	the entry process	2689:2705	Defining the AAV-AAVR interface in more detail is important to understand how AAV engages with its cellular receptor and how the receptor facilitates the entry process.
28679762	2	13	theme	Adeno-associated	244:259	arg1	virus					261:265	Adeno-associated virus	244:265	Adeno-associated virus receptor (AAVR) (also named KIAA0319L)	244:304	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	9	14	theme	other	1623:1627	arg1	-8					1663:1664	-8	1663:1664	-8	1663:1664	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	9	14	theme	other	1623:1627	arg1	serotypes					1633:1641	other AAV serotypes	1623:1641	other AAV serotypes	1623:1641	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	9	14	theme	other	1623:1627	arg1	AAV1					1654:1657	AAV1	1654:1657	AAV1	1654:1657	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	7	15	theme	polycystic	1392:1401	arg1	PKD					1419:1421	PKD	1419:1421	PKD	1419:1421	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	15	theme	polycystic	1392:1401	arg1	disease					1410:1416	polycystic kidney disease	1392:1416	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	4	16	theme	virus	647:651	arg1	assay					661:665	a virus overlay assay	645:665	a virus overlay assay	645:665	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	10	17	theme	same	1900:1903	arg1	receptor.IMPORTANCE					1905:1923	the same receptor.IMPORTANCE	1896:1923	the same receptor.IMPORTANCE	1896:1923	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	16	18	theme	PKD	2868:2870	arg1	AAVR					2883:2886	AAVR	2883:2886	AAVR	2883:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	16	18	theme	PKD	2868:2870	arg1	domains					2872:2878	the Ig-like PKD domains	2856:2878	the Ig-like PKD domains of AAVR	2856:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	7	19	theme	second	1377:1382	arg1	PKD2					1439:1442	PKD2	1439:1442	PKD2	1439:1442	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	19	theme	second	1377:1382	arg1	domain					1431:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain	1373:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	1	20	theme	specific	186:193	arg1	glycans					203:209	specific surface glycans	186:209	specific surface glycans	186:209	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	11	21	theme	AAV	2093:2095	arg1	cycle					2102:2106	the AAV life cycle	2089:2106	the AAV life cycle	2089:2106	However, fundamental aspects of the AAV life cycle, including how AAV interacts with host cellular factors to facilitate infection, are only partly understood.
28679762	10	22	theme	past	1934:1937	arg1	decade					1939:1944	the past decade	1930:1944	the past decade	1930:1944	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	16	23	theme	AAVR	2883:2886	arg1	AAVR					2883:2886	AAVR	2883:2886	AAVR	2883:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	16	23	theme	AAVR	2883:2886	arg1	domains					2872:2878	the Ig-like PKD domains	2856:2878	the Ig-like PKD domains of AAVR	2856:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	5	24	gly	glycoprotein	1003:1014	arg1	glycoprotein					1003:1014	this glycoprotein	998:1014	this glycoprotein	998:1014	By establishing a purification procedure, performing further protein separation by two-dimensional electrophoresis, and utilizing mass spectrometry, we now show that this glycoprotein is identical to AAVR.
28679762	12	25	theme	vector	2278:2283	arg1	efficiency					2298:2307	AAV vector transduction efficiency	2274:2307	AAV vector transduction efficiency	2274:2307	In particular, AAV receptors contribute significantly to AAV vector transduction efficiency and tropism.
28679762	1	26	theme	Adeno-associated	112:127	arg1	virus					129:133	Adeno-associated virus	112:133	Adeno-associated virus (AAV) entry	112:145	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	1	26	theme	Adeno-associated	112:127	arg1	AAV					136:138	AAV	136:138	AAV	136:138	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	14	27	theme	viral	2519:2523	arg1	transduction					2525:2536	viral transduction	2519:2536	viral transduction	2519:2536	AAVR binds directly to AAV2 particles and is rate limiting for viral transduction.
28679762	12	28	theme	AAV	2232:2234	arg1	receptors					2236:2244	AAV receptors	2232:2244	AAV receptors	2232:2244	In particular, AAV receptors contribute significantly to AAV vector transduction efficiency and tropism.
28679762	6	29	theme	functional	1166:1175	arg1	transduction					1177:1188	functional transduction	1166:1188	functional transduction	1166:1188	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	16	30	theme	AAV	2810:2812	arg1	serotypes					2814:2822	different AAV serotypes	2800:2822	different AAV serotypes	2800:2822	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	5	31	theme	protein	893:899	arg1	separation					901:910	further protein separation	885:910	further protein separation by two-dimensional electrophoresis	885:945	By establishing a purification procedure, performing further protein separation by two-dimensional electrophoresis, and utilizing mass spectrometry, we now show that this glycoprotein is identical to AAVR.
28679762	1	32	theme	virus	129:133	arg1	entry					141:145	Adeno-associated virus (AAV) entry	112:145	Adeno-associated virus (AAV) entry	112:145	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	11	33	theme	cellular	2147:2154	arg1	factors					2156:2162	host cellular factors	2142:2162	host cellular factors	2142:2162	However, fundamental aspects of the AAV life cycle, including how AAV interacts with host cellular factors to facilitate infection, are only partly understood.
28679762	11	34	theme	life	2097:2100	arg1	cycle					2102:2106	the AAV life cycle	2089:2106	the AAV life cycle	2089:2106	However, fundamental aspects of the AAV life cycle, including how AAV interacts with host cellular factors to facilitate infection, are only partly understood.
28679762	16	35	theme	AAV-AAVR	2732:2739	arg1	interactions					2741:2752	AAV-AAVR interactions	2732:2752	AAV-AAVR interactions	2732:2752	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	10	36	dep	interactions	1878:1889	arg1	emerged					1964:1970	emerged	1964:1970	have emerged as leading gene delivery tools for therapeutic applications and biomedical research	1959:2054	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	0	37	theme	AAV	98:100	arg1	Receptor					102:109	the Cellular AAV Receptor	85:109	the Cellular AAV Receptor	85:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	5	38	theme	mass	962:965	arg1	spectrometry					967:978	mass spectrometry	962:978	mass spectrometry	962:978	By establishing a purification procedure, performing further protein separation by two-dimensional electrophoresis, and utilizing mass spectrometry, we now show that this glycoprotein is identical to AAVR.
28679762	11	39	theme	cycle	2102:2106	arg1	aspects					2078:2084	fundamental aspects	2066:2084	fundamental aspects	2066:2084	However, fundamental aspects of the AAV life cycle, including how AAV interacts with host cellular factors to facilitate infection, are only partly understood.
28679762	4	40	theme	major	701:705	arg1	protein					720:726	the major AAV2 binding protein	697:726	the major AAV2 binding protein in membrane preparations of human cells	697:766	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	0	41	theme	Adeno-associated	0:15	arg1	AAV					24:26	AAV	24:26	AAV	24:26	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	0	41	theme	Adeno-associated	0:15	arg1	Virus					17:21	Adeno-associated Virus	0:21	Adeno-associated Virus (AAV) Serotypes	0:37	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	17	42	theme	AAVR	2939:2942	arg1	engagement					2944:2953	AAVR engagement	2939:2953	AAVR engagement	2939:2953	These findings reveal an unexpected divergence of AAVR engagement within these parvoviruses.
28679762	16	43	theme	Ig-like	2860:2866	arg1	AAVR					2883:2886	AAVR	2883:2886	AAVR	2883:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	16	43	theme	Ig-like	2860:2866	arg1	domains					2872:2878	the Ig-like PKD domains	2856:2878	the Ig-like PKD domains of AAVR	2856:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	2	44	theme	AAV	403:405	arg1	serotypes					407:415	multiple AAV serotypes	394:415	multiple AAV serotypes	394:415	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	44	theme	AAV	403:405	arg1	serotypes					455:463	the evolutionarily distant serotypes	428:463	the evolutionarily distant serotypes AAV2 and AAV5	428:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	4	45	theme	binding	712:718	arg1	protein					720:726	the major AAV2 binding protein	697:726	the major AAV2 binding protein in membrane preparations of human cells	697:766	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	7	46	theme	disease	1410:1416	arg1	PKD2					1439:1442	PKD2	1439:1442	PKD2	1439:1442	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	46	theme	disease	1410:1416	arg1	domain					1431:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain	1373:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	2	47	attach	derived	381:387	arg1	serotypes					407:415	multiple AAV serotypes	394:415	multiple AAV serotypes	394:415	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	47	attach	derived	381:387	arg2	vectors					373:379	vectors	373:379	vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5	373:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	47	attach	derived	381:387	arg1	serotypes					455:463	the evolutionarily distant serotypes	428:463	the evolutionarily distant serotypes AAV2 and AAV5	428:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	48	theme	distant	447:453	arg1	serotypes					455:463	the evolutionarily distant serotypes	428:463	the evolutionarily distant serotypes AAV2 and AAV5	428:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	48	theme	distant	447:453	arg1	AAV5					474:477	AAV5	474:477	AAV5	474:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	48	theme	distant	447:453	arg1	AAV2					465:468	AAV2	465:468	AAV2	465:468	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	6	49	link	N-linked	1068:1075	arg1	protein					1090:1096	an N-linked glycosylated protein	1065:1096	an N-linked glycosylated protein	1065:1096	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	6	49	link	N-linked	1068:1075	arg1	AAVR					1057:1060	AAVR	1057:1060	AAVR	1057:1060	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	2	50	theme	vectors	373:379	arg1	transduction					357:368	the transduction	353:368	the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5	353:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	15	51	theme	cellular	2638:2645	arg1	receptor					2647:2654	its cellular receptor	2634:2654	its cellular receptor	2634:2654	Defining the AAV-AAVR interface in more detail is important to understand how AAV engages with its cellular receptor and how the receptor facilitates the entry process.
28679762	7	52	theme	overlay	1273:1279	arg1	assays					1281:1286	virus overlay assays	1267:1286	virus overlay assays with individual domains	1267:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	8	53	theme	first	1530:1534	arg1	domain					1563:1568	PKD domain	1559:1568	PKD domain (PKD1)	1559:1575	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	53	theme	first	1530:1534	arg1	PKD1					1571:1574	PKD1	1571:1574	PKD1	1571:1574	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	53	theme	first	1530:1534	arg1	AAVR					1580:1583	AAVR	1580:1583	AAVR	1580:1583	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	10	54	theme	shared	1773:1778	arg1	dependence					1780:1789	their shared dependence	1767:1789	their shared dependence on AAVR as a critical entry receptor	1767:1826	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	2	55	dep	serotypes	455:463	arg1	serotypes					455:463	the evolutionarily distant serotypes	428:463	the evolutionarily distant serotypes AAV2 and AAV5	428:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	55	dep	serotypes	455:463	arg1	AAV5					474:477	AAV5	474:477	AAV5	474:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	55	dep	serotypes	455:463	arg1	AAV2					465:468	AAV2	465:468	AAV2	465:468	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	7	56	theme	AAVR	1474:1477	arg1	AAVR					1474:1477	AAVR	1474:1477	AAVR	1474:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	56	theme	AAVR	1474:1477	arg1	ectodomain					1460:1469	the ectodomain	1456:1469	the ectodomain of AAVR	1456:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	13	57	theme	AAV	2346:2348	arg1	AAVR					2360:2363	AAVR	2360:2363	AAVR	2360:2363	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	57	theme	AAV	2346:2348	arg1	receptor					2350:2357	The recently identified AAV receptor	2322:2357	The recently identified AAV receptor (AAVR)	2322:2364	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	57	theme	AAV	2346:2348	arg1	receptor					2380:2387	a key host receptor	2369:2387	a key host receptor for multiple serotypes, including the most studied serotype, AAV2	2369:2453	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	17	58	theme	unexpected	2914:2923	arg1	divergence					2925:2934	an unexpected divergence	2911:2934	an unexpected divergence of AAVR engagement within these parvoviruses	2911:2979	These findings reveal an unexpected divergence of AAVR engagement within these parvoviruses.
28679762	10	59	theme	critical	1804:1811	arg1	receptor					1819:1826	a critical entry receptor	1802:1826	a critical entry receptor	1802:1826	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	4	60	theme	human	756:760	arg1	cells					762:766	human cells	756:766	human cells	756:766	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	17	61	theme	engagement	2944:2953	arg1	divergence					2925:2934	an unexpected divergence	2911:2934	an unexpected divergence of AAVR engagement within these parvoviruses	2911:2979	These findings reveal an unexpected divergence of AAVR engagement within these parvoviruses.
28679762	6	62	theme	N-linked	1068:1075	arg1	protein					1090:1096	an N-linked glycosylated protein	1065:1096	an N-linked glycosylated protein	1065:1096	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	6	62	theme	N-linked	1068:1075	arg1	AAVR					1057:1060	AAVR	1057:1060	AAVR	1057:1060	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	10	63	theme	delivery	1988:1995	arg1	tools					1997:2001	gene delivery tools	1983:2001	gene delivery tools for therapeutic applications and biomedical research	1983:2054	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	15	64	from	interface	2561:2569	arg1	detail					2579:2584	more detail	2574:2584	more detail	2574:2584	Defining the AAV-AAVR interface in more detail is important to understand how AAV engages with its cellular receptor and how the receptor facilitates the entry process.
28679762	1	65	theme	proteinaceous	217:229	arg1	s					240:240	a proteinaceous receptor(s)	215:241	a proteinaceous receptor(s)	215:241	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	7	66	theme	complementation	1222:1236	arg1	combination					1199:1209	a combination	1197:1209	a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains	1197:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	10	67	theme	biomedical	2036:2045	arg1	research					2047:2054	biomedical research	2036:2054	biomedical research	2036:2054	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	10	68	theme	different	1829:1837	arg1	serotypes					1843:1851	different AAV serotypes	1829:1851	different AAV serotypes	1829:1851	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	16	69	theme	discrete	2829:2836	arg1	interactions					2838:2849	discrete interactions	2829:2849	discrete interactions with the Ig-like PKD domains of AAVR	2829:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	2	70	theme	essential	312:320	arg1	receptor					267:274	Adeno-associated virus receptor	244:274	Adeno-associated virus receptor (AAVR) (also named KIAA0319L)	244:304	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	70	theme	essential	312:320	arg1	receptor					331:338	an essential cellular receptor	309:338	an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5	309:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	11	71	theme	fundamental	2066:2076	arg1	aspects					2078:2084	fundamental aspects	2066:2084	fundamental aspects	2066:2084	However, fundamental aspects of the AAV life cycle, including how AAV interacts with host cellular factors to facilitate infection, are only partly understood.
28679762	16	72	contain	have	2824:2827	arg2	interactions					2838:2849	discrete interactions	2829:2849	discrete interactions with the Ig-like PKD domains of AAVR	2829:2886	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	16	72	contain	have	2824:2827	arg1	serotypes					2814:2822	different AAV serotypes	2800:2822	different AAV serotypes	2800:2822	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	14	73	dep	limiting	2506:2513	arg1	rate					2501:2504	rate	2501:2504	rate	2501:2504	AAVR binds directly to AAV2 particles and is rate limiting for viral transduction.
28679762	13	74	theme	studied	2432:2438	arg1	AAV2					2450:2453	AAV2	2450:2453	AAV2	2450:2453	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	74	theme	studied	2432:2438	arg1	serotype					2440:2447	the most studied serotype	2423:2447	the most studied serotype	2423:2447	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	0	75	with	Interactions	56:67	arg1	Domains					74:80	Domains	74:80	Domains of the Cellular AAV Receptor	74:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	0	75	with	Interactions	56:67	arg1	Receptor					102:109	the Cellular AAV Receptor	85:109	the Cellular AAV Receptor	85:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	2	76	theme	virus	261:265	arg1	receptor					267:274	Adeno-associated virus receptor	244:274	Adeno-associated virus receptor (AAVR) (also named KIAA0319L)	244:304	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	76	theme	virus	261:265	arg1	AAVR					277:280	AAVR	277:280	AAVR	277:280	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	76	theme	virus	261:265	arg1	receptor					331:338	an essential cellular receptor	309:338	an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5	309:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	7	77	theme	repeat	1424:1429	arg1	PKD2					1439:1442	PKD2	1439:1442	PKD2	1439:1442	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	77	theme	repeat	1424:1429	arg1	domain					1431:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain	1373:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	11	78	theme	host	2142:2145	arg1	factors					2156:2162	host cellular factors	2142:2162	host cellular factors	2142:2162	However, fundamental aspects of the AAV life cycle, including how AAV interacts with host cellular factors to facilitate infection, are only partly understood.
28679762	7	79	with	constructs	1252:1261	arg1	domains					1304:1310	individual domains	1293:1310	individual domains	1293:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	1	80	with	interactions	168:179	arg1	s					240:240	a proteinaceous receptor(s)	215:241	a proteinaceous receptor(s)	215:241	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	1	80	with	interactions	168:179	arg1	glycans					203:209	specific surface glycans	186:209	specific surface glycans	186:209	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	9	81	theme	AAV	1629:1631	arg1	-8					1663:1664	-8	1663:1664	-8	1663:1664	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	9	81	theme	AAV	1629:1631	arg1	serotypes					1633:1641	other AAV serotypes	1623:1641	other AAV serotypes	1623:1641	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	9	81	theme	AAV	1629:1631	arg1	AAV1					1654:1657	AAV1	1654:1657	AAV1	1654:1657	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	7	82	theme	kidney	1403:1408	arg1	PKD					1419:1421	PKD	1419:1421	PKD	1419:1421	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	82	theme	kidney	1403:1408	arg1	disease					1410:1416	polycystic kidney disease	1392:1416	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	3	83	theme	AAV-AAVR	528:535	arg1	interaction					537:547	the AAV-AAVR interaction	524:547	the AAV-AAVR interaction	524:547	Here, we further biochemically characterize the AAV-AAVR interaction and define the domains within the ectodomain of AAVR that facilitate this interaction.
28679762	12	84	theme	AAV	2274:2276	arg1	efficiency					2298:2307	AAV vector transduction efficiency	2274:2307	AAV vector transduction efficiency	2274:2307	In particular, AAV receptors contribute significantly to AAV vector transduction efficiency and tropism.
28679762	7	85	theme	Ig-like	1384:1390	arg1	PKD2					1439:1442	PKD2	1439:1442	PKD2	1439:1442	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	85	theme	Ig-like	1384:1390	arg1	domain					1431:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain	1373:1436	the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR	1373:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	86	with	assays	1281:1286	arg1	domains					1304:1310	individual domains	1293:1310	individual domains	1293:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	1	87	theme	surface	195:201	arg1	glycans					203:209	specific surface glycans	186:209	specific surface glycans	186:209	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28679762	7	88	from	present	1445:1451	arg1	AAVR					1474:1477	AAVR	1474:1477	AAVR	1474:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	88	from	present	1445:1451	arg1	ectodomain					1460:1469	the ectodomain	1456:1469	the ectodomain of AAVR	1456:1477	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	10	89	theme	AAV	1947:1949	arg1	vectors					1951:1957	AAV vectors	1947:1957	AAV vectors	1947:1957	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	12	90	theme	transduction	2285:2296	arg1	efficiency					2298:2307	AAV vector transduction efficiency	2274:2307	AAV vector transduction efficiency	2274:2307	In particular, AAV receptors contribute significantly to AAV vector transduction efficiency and tropism.
28679762	10	91	with	interactions	1878:1889	arg1	receptor.IMPORTANCE					1905:1923	the same receptor.IMPORTANCE	1896:1923	the same receptor.IMPORTANCE	1896:1923	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	16	92	theme	different	2800:2808	arg1	serotypes					2814:2822	different AAV serotypes	2800:2822	different AAV serotypes	2800:2822	Here, we further define AAV-AAVR interactions, genetically and biochemically, and show that different AAV serotypes have discrete interactions with the Ig-like PKD domains of AAVR.
28679762	13	93	theme	multiple	2393:2400	arg1	serotypes					2402:2410	multiple serotypes	2393:2410	multiple serotypes	2393:2410	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	93	theme	multiple	2393:2400	arg1	serotype					2440:2447	the most studied serotype	2423:2447	the most studied serotype	2423:2447	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	3	94	theme	AAVR	597:600	arg1	AAVR					597:600	AAVR	597:600	AAVR that facilitate this interaction	597:633	Here, we further biochemically characterize the AAV-AAVR interaction and define the domains within the ectodomain of AAVR that facilitate this interaction.
28679762	3	94	theme	AAVR	597:600	arg1	ectodomain					583:592	the ectodomain	579:592	the ectodomain of AAVR that facilitate this interaction	579:633	Here, we further biochemically characterize the AAV-AAVR interaction and define the domains within the ectodomain of AAVR that facilitate this interaction.
28679762	5	95	theme	further	885:891	arg1	separation					901:910	further protein separation	885:910	further protein separation by two-dimensional electrophoresis	885:945	By establishing a purification procedure, performing further protein separation by two-dimensional electrophoresis, and utilizing mass spectrometry, we now show that this glycoprotein is identical to AAVR.
28679762	4	96	with	glycoprotein	785:796	arg1	mass					815:818	a molecular mass	803:818	a molecular mass of 150 kDa	803:829	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	6	97	theme	AAV2	1150:1153	arg1	binding					1155:1161	AAV2 binding	1150:1161	AAV2 binding	1150:1161	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	4	98	theme	overlay	653:659	arg1	assay					661:665	a virus overlay assay	645:665	a virus overlay assay	645:665	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	5	99	theme	purification	850:861	arg1	procedure					863:871	a purification procedure	848:871	a purification procedure	848:871	By establishing a purification procedure, performing further protein separation by two-dimensional electrophoresis, and utilizing mass spectrometry, we now show that this glycoprotein is identical to AAVR.
28679762	9	100	theme	PKD1	1692:1695	arg1	combination					1677:1687	a combination	1675:1687	a combination of PKD1 and PKD2 for optimal transduction	1675:1729	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	2	101	dep	receptor	267:274	arg1	named					289:293	named	289:293	named KIAA0319L	289:303	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	0	102	theme	Cellular	89:96	arg1	Receptor					102:109	the Cellular AAV Receptor	85:109	the Cellular AAV Receptor	85:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	14	103	theme	AAV2	2479:2482	arg1	particles					2484:2492	AAV2 particles	2479:2492	AAV2 particles	2479:2492	AAVR binds directly to AAV2 particles and is rate limiting for viral transduction.
28679762	9	104	theme	PKD2	1701:1704	arg1	combination					1677:1687	a combination	1675:1687	a combination of PKD1 and PKD2 for optimal transduction	1675:1729	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	7	105	theme	deletion	1243:1250	arg1	constructs					1252:1261	deletion constructs	1243:1261	deletion constructs	1243:1261	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	0	106	theme	Receptor	102:109	arg1	Domains					74:80	Domains	74:80	Domains of the Cellular AAV Receptor	74:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	0	106	theme	Receptor	102:109	arg1	Receptor					102:109	the Cellular AAV Receptor	85:109	the Cellular AAV Receptor	85:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	4	107	from	protein	720:726	arg1	preparations					740:751	membrane preparations	731:751	membrane preparations of human cells	731:766	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	13	108	theme	key	2371:2373	arg1	receptor					2380:2387	a key host receptor	2369:2387	a key host receptor for multiple serotypes, including the most studied serotype, AAV2	2369:2453	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	108	theme	key	2371:2373	arg1	receptor					2350:2357	The recently identified AAV receptor	2322:2357	The recently identified AAV receptor (AAVR)	2322:2364	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	9	109	theme	optimal	1710:1716	arg1	transduction					1718:1729	optimal transduction	1710:1729	optimal transduction	1710:1729	Furthermore, other AAV serotypes, including AAV1 and -8, require a combination of PKD1 and PKD2 for optimal transduction.
28679762	4	110	theme	membrane	731:738	arg1	preparations					740:751	membrane preparations	731:751	membrane preparations of human cells	731:766	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	15	111	theme	more	2574:2577	arg1	detail					2579:2584	more detail	2574:2584	more detail	2574:2584	Defining the AAV-AAVR interface in more detail is important to understand how AAV engages with its cellular receptor and how the receptor facilitates the entry process.
28679762	0	112	theme	Virus	17:21	arg1	Serotypes					29:37	Adeno-associated Virus (AAV) Serotypes	0:37	Adeno-associated Virus (AAV) Serotypes	0:37	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	10	113	from	dependence	1780:1789	arg1	AAVR					1794:1797	AAVR	1794:1797	AAVR	1794:1797	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	7	114	theme	individual	1293:1302	arg1	domains					1304:1310	individual domains	1293:1310	individual domains	1293:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	6	115	gly	glycosylated	1077:1088	arg1	protein					1090:1096	an N-linked glycosylated protein	1065:1096	an N-linked glycosylated protein	1065:1096	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	6	115	gly	glycosylated	1077:1088	arg1	AAVR					1057:1060	AAVR	1057:1060	AAVR	1057:1060	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	2	116	dep	named	289:293	arg1	also					284:287	also	284:287	also	284:287	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	4	117	gly	glycoprotein	785:796	arg1	glycoprotein					785:796	a glycoprotein	783:796	a glycoprotein with a molecular mass of 150 kDa	783:829	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	5	118	theme	two-dimensional	915:929	arg1	electrophoresis					931:945	two-dimensional electrophoresis	915:945	two-dimensional electrophoresis	915:945	By establishing a purification procedure, performing further protein separation by two-dimensional electrophoresis, and utilizing mass spectrometry, we now show that this glycoprotein is identical to AAVR.
28679762	2	119	theme	multiple	394:401	arg1	serotypes					407:415	multiple AAV serotypes	394:415	multiple AAV serotypes	394:415	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	119	theme	multiple	394:401	arg1	serotypes					455:463	the evolutionarily distant serotypes	428:463	the evolutionarily distant serotypes AAV2 and AAV5	428:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	15	120	dep	understand	2602:2611	arg1	engages					2621:2627	engages	2621:2627	engages with its cellular receptor	2621:2654	Defining the AAV-AAVR interface in more detail is important to understand how AAV engages with its cellular receptor and how the receptor facilitates the entry process.
28679762	15	120	dep	understand	2602:2611	arg1	facilitates					2677:2687	facilitates	2677:2687	facilitates the entry process	2677:2705	Defining the AAV-AAVR interface in more detail is important to understand how AAV engages with its cellular receptor and how the receptor facilitates the entry process.
28679762	4	121	theme	AAV2	707:710	arg1	protein					720:726	the major AAV2 binding protein	697:726	the major AAV2 binding protein in membrane preparations of human cells	697:766	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	7	122	theme	virus	1267:1271	arg1	assays					1281:1286	virus overlay assays	1267:1286	virus overlay assays with individual domains	1267:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	0	123	theme	Distinctive	44:54	arg1	Interactions					56:67	Distinctive Interactions	44:67	Distinctive Interactions with Domains of the Cellular AAV Receptor	44:109	Adeno-associated Virus (AAV) Serotypes Have Distinctive Interactions with Domains of the Cellular AAV Receptor.
28679762	13	124	theme	identified	2335:2344	arg1	AAVR					2360:2363	AAVR	2360:2363	AAVR	2360:2363	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	124	theme	identified	2335:2344	arg1	receptor					2350:2357	The recently identified AAV receptor	2322:2357	The recently identified AAV receptor (AAVR)	2322:2364	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	124	theme	identified	2335:2344	arg1	receptor					2380:2387	a key host receptor	2369:2387	a key host receptor for multiple serotypes, including the most studied serotype, AAV2	2369:2453	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	8	125	theme	membrane-distal	1542:1556	arg1	domain					1563:1568	PKD domain	1559:1568	PKD domain (PKD1)	1559:1575	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	125	theme	membrane-distal	1542:1556	arg1	PKD1					1571:1574	PKD1	1571:1574	PKD1	1571:1574	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	125	theme	membrane-distal	1542:1556	arg1	AAVR					1580:1583	AAVR	1580:1583	AAVR	1580:1583	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	10	126	theme	entry	1813:1817	arg1	receptor					1819:1826	a critical entry receptor	1802:1826	a critical entry receptor	1802:1826	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	6	127	theme	glycosylated	1077:1088	arg1	protein					1090:1096	an N-linked glycosylated protein	1065:1096	an N-linked glycosylated protein	1065:1096	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	6	127	theme	glycosylated	1077:1088	arg1	AAVR					1057:1060	AAVR	1057:1060	AAVR	1057:1060	While we find that AAVR is an N-linked glycosylated protein, this glycosylation is not a strict requirement for AAV2 binding or functional transduction.
28679762	8	128	theme	PKD	1559:1561	arg1	domain					1563:1568	PKD domain	1559:1568	PKD domain (PKD1)	1559:1575	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	128	theme	PKD	1559:1561	arg1	PKD1					1571:1574	PKD1	1571:1574	PKD1	1571:1574	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	8	128	theme	PKD	1559:1561	arg1	AAVR					1580:1583	AAVR	1580:1583	AAVR	1580:1583	In contrast, AAV5 interacts primarily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.
28679762	13	129	theme	host	2375:2378	arg1	receptor					2380:2387	a key host receptor	2369:2387	a key host receptor for multiple serotypes, including the most studied serotype, AAV2	2369:2453	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	13	129	theme	host	2375:2378	arg1	receptor					2350:2357	The recently identified AAV receptor	2322:2357	The recently identified AAV receptor (AAVR)	2322:2364	The recently identified AAV receptor (AAVR) is a key host receptor for multiple serotypes, including the most studied serotype, AAV2.
28679762	7	130	from	ectodomain	1460:1469	arg1	present					1445:1451	present	1445:1451	present	1445:1451	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	7	131	theme	genetic	1214:1220	arg1	complementation					1222:1236	genetic complementation	1214:1236	genetic complementation with deletion constructs and virus overlay assays with individual domains	1214:1310	Using a combination of genetic complementation with deletion constructs and virus overlay assays with individual domains, we find that AAV2 functionally interacts predominantly with the second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of AAVR.
28679762	10	132	theme	gene	1983:1986	arg1	tools					1997:2001	gene delivery tools	1983:2001	gene delivery tools for therapeutic applications and biomedical research	1983:2054	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	10	133	theme	AAV	1839:1841	arg1	serotypes					1843:1851	different AAV serotypes	1829:1851	different AAV serotypes	1829:1851	These results suggest that despite their shared dependence on AAVR as a critical entry receptor, different AAV serotypes have evolved distinctive interactions with the same receptor.IMPORTANCE Over the past decade, AAV vectors have emerged as leading gene delivery tools for therapeutic applications and biomedical research.
28679762	4	134	theme	cells	762:766	arg1	preparations					740:751	membrane preparations	731:751	membrane preparations of human cells	731:766	By using a virus overlay assay, it was previously shown that the major AAV2 binding protein in membrane preparations of human cells corresponds to a glycoprotein with a molecular mass of 150 kDa.
28679762	2	135	theme	cellular	322:329	arg1	receptor					267:274	Adeno-associated virus receptor	244:274	Adeno-associated virus receptor (AAVR) (also named KIAA0319L)	244:304	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	2	135	theme	cellular	322:329	arg1	receptor					331:338	an essential cellular receptor	309:338	an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5	309:477	Adeno-associated virus receptor (AAVR) (also named KIAA0319L) is an essential cellular receptor required for the transduction of vectors derived from multiple AAV serotypes, including the evolutionarily distant serotypes AAV2 and AAV5.
28679762	1	136	theme	receptor	231:238	arg1	s					240:240	a proteinaceous receptor(s)	215:241	a proteinaceous receptor(s)	215:241	Adeno-associated virus (AAV) entry is determined by its interactions with specific surface glycans and a proteinaceous receptor(s).
28634213	4	0	theme	protein	750:756	arg1	PERK					785:788	PERK	785:788	PERK	785:788	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	0	theme	protein	750:756	arg1	kinase					777:782	protein kinase RNA-like ER kinase	750:782	protein kinase RNA-like ER kinase (PERK) expression	750:800	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	1	theme	RNA-like	765:772	arg1	PERK					785:788	PERK	785:788	PERK	785:788	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	1	theme	RNA-like	765:772	arg1	kinase					777:782	protein kinase RNA-like ER kinase	750:782	protein kinase RNA-like ER kinase (PERK) expression	750:800	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	3	2	theme	fish-derived	611:622	arg1	patients					642:649	fish-derived, ω-3-supplemented patients	611:649	fish-derived, ω-3-supplemented patients with MCI	611:658	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	1	3	from	phagocytosis	280:291	arg1	defective					248:256	defective	248:256	defective	248:256	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	4	4	theme	ApoEe3/e4	955:963	arg1	subgroup					965:972	the ApoEe3/e4 subgroup	951:972	the ApoEe3/e4 subgroup	951:972	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	5	theme	cognitive	1840:1848	arg1	impairment					1850:1859	mild cognitive impairment	1835:1859	mild cognitive impairment	1835:1859	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	0	6	with	patients	112:119	arg1	impairment					141:150	mild cognitive impairment	126:150	mild cognitive impairment	126:150	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	7	theme	expression	791:800	arg1	type					842:845	intermediate M1-M2 Mϕ type	820:845	intermediate M1-M2 Mϕ type	820:845	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	7	theme	expression	791:800	arg1	phagocytosis					806:817	Aβ phagocytosis	803:817	Aβ phagocytosis	803:817	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	7	theme	expression	791:800	arg1	increase					738:745	an increase	735:745	an increase of protein kinase RNA-like ER kinase (PERK) expression	735:800	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	7	theme	expression	791:800	arg1	rate					891:894	a Mini-Mental State Examination (MMSE) rate	852:894	a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year	852:928	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	1	8	from	defective	248:256	arg1	phagocytosis					280:291	amyloid-β1-42 (Aβ) phagocytosis	261:291	amyloid-β1-42 (Aβ) phagocytosis	261:291	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	1	8	from	defective	248:256	arg1	Aβ					276:277	Aβ	276:277	Aβ	276:277	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	4	9	theme	Aβ	803:804	arg1	phagocytosis					806:817	Aβ phagocytosis	803:817	Aβ phagocytosis	803:817	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	0	10	theme	cognitive	131:139	arg1	impairment					141:150	mild cognitive impairment	126:150	mild cognitive impairment	126:150	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	3	11	theme	protein	517:523	arg1	UPR					535:537	UPR	535:537	UPR	535:537	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	3	11	theme	protein	517:523	arg1	response					525:532	the unfolded protein response	504:532	the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress	504:575	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	4	12	theme	kinase	777:782	arg1	expression					791:800	protein kinase RNA-like ER kinase (PERK) expression	750:800	protein kinase RNA-like ER kinase (PERK) expression	750:800	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	13	theme	MMSE	1020:1023	arg1	rate					1025:1028	an MMSE rate	1017:1028	an MMSE rate of change of -3.2 points per year	1017:1062	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	14	theme	amyloid-β	1780:1788	arg1	phagocytosis					1790:1801	amyloid-β phagocytosis	1780:1801	amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment	1780:1859	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	15	theme	immune	1436:1441	arg1	clearance					1443:1451	immune clearance	1436:1451	immune clearance of Aβ	1436:1457	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	5	16	theme	ω-3	1107:1109	arg1	emulsion					1111:1118	fish-derived ω-3 emulsion	1094:1118	fish-derived ω-3 emulsion	1094:1118	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	4	17	theme	divergent	994:1002	arg1	results					1004:1010	individually divergent results	981:1010	individually divergent results	981:1010	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	18	theme	protein	1751:1757	arg1	response					1759:1766	the unfolded protein response	1738:1766	the unfolded protein response	1738:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	1	19	theme	low	302:304	arg1	resistance					306:315	low resistance	302:315	low resistance to apoptosis by Aβ	302:334	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	7	20	theme	proapoptotic	1408:1419	arg1	genes					1421:1425	decrease proapoptotic genes	1399:1425	decrease proapoptotic genes	1399:1425	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	0	21	theme	amyloid-β	71:79	arg1	phagocytosis					81:92	amyloid-β phagocytosis	71:92	amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment	71:150	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	22	from	Patients	661:668	arg1	subgroup					706:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	23	theme	cytoprotective	1374:1387	arg1	genes					1389:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	2	24	theme	Aβ	438:439	arg1	phagocytosis					441:452	Aβ phagocytosis	438:452	Aβ phagocytosis by Mϕs of patients with MCI	438:480	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	7	25	dep	clearance	1443:1451	arg1	associated					1468:1477	associated	1468:1477	are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1464:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	2	26	theme	resolvin	407:414	arg1	mediator					397:404	the ω-3 mediator	389:404	the ω-3 mediator	389:404	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	2	26	theme	resolvin	407:414	arg1	D1					416:417	resolvin D1	407:417	resolvin D1	407:417	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	7	27	theme	MMSE	1496:1499	arg1	rate					1501:1504	an improved MMSE rate	1484:1504	an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1484:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	5	28	theme	UPR	1168:1170	arg1	signature					1176:1184	UPR RNA signature	1168:1184	UPR RNA signature	1168:1184	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	0	29	theme	Omega-3	0:6	arg1	acids					14:18	Omega-3 fatty acids	0:18	Omega-3 fatty acids	0:18	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	30	theme	points	1048:1053	arg1	change					1033:1038	change	1033:1038	change of -3.2 points per year	1033:1062	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	31	theme	fish-derived	1347:1358	arg1	genes					1389:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	32	theme	Mini-Mental	854:864	arg1	MMSE					885:888	MMSE	885:888	MMSE	885:888	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	32	theme	Mini-Mental	854:864	arg1	Examination					872:882	a Mini-Mental State Examination	852:882	a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year	852:928	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	33	theme	e3/e3	700:704	arg1	subgroup					706:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	5	34	theme	PERK	1147:1150	arg1	expression					1152:1161	PERK expression	1147:1161	PERK expression	1147:1161	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	7	35	with	patients	1821:1828	arg1	impairment					1850:1859	mild cognitive impairment	1835:1859	mild cognitive impairment	1835:1859	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	36	theme	Examination	872:882	arg1	rate					891:894	a Mini-Mental State Examination (MMSE) rate	852:894	a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year	852:928	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	3	37	theme	endoplasmic	543:553	arg1	reticulum					555:563	endoplasmic reticulum	543:563	endoplasmic reticulum (ER) stress	543:575	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	3	37	theme	endoplasmic	543:553	arg1	ER					566:567	ER	566:567	ER	566:567	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	5	38	theme	ER	1201:1202	arg1	signature					1211:1219	ER stress signature	1201:1219	ER stress signature	1201:1219	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	0	39	theme	protein	42:48	arg1	response					50:57	the unfolded protein response	29:57	the unfolded protein response	29:57	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	3	40	dep	fish-derived	611:622	arg1	ω-3-supplemented					625:640	ω-3-supplemented	625:640	ω-3-supplemented	625:640	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	4	41	theme	E	692:692	arg1	subgroup					706:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	1	42	theme	mild	212:215	arg1	impairment					227:236	mild cognitive impairment	212:236	mild cognitive impairment	212:236	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	4	43	theme	ApoE	695:698	arg1	subgroup					706:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	2	44	theme	Omega-3	337:343	arg1	ω-3s					358:361	ω-3s	358:361	ω-3s	358:361	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	2	44	theme	Omega-3	337:343	arg1	acids					351:355	Omega-3 fatty acids	337:355	Omega-3 fatty acids (ω-3s)	337:362	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	2	45	with	patients	464:471	arg1	MCI					478:480	MCI	478:480	MCI	478:480	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	1	46	theme	impairment	227:236	arg1	Macrophages					153:163	Macrophages	153:163	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI)	153:242	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	1	46	theme	impairment	227:236	arg1	Mϕs					166:168	Mϕs	166:168	Mϕs	166:168	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	4	47	theme	change	899:904	arg1	type					842:845	intermediate M1-M2 Mϕ type	820:845	intermediate M1-M2 Mϕ type	820:845	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	47	theme	change	899:904	arg1	phagocytosis					806:817	Aβ phagocytosis	803:817	Aβ phagocytosis	803:817	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	47	theme	change	899:904	arg1	increase					738:745	an increase	735:745	an increase of protein kinase RNA-like ER kinase (PERK) expression	735:800	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	47	theme	change	899:904	arg1	rate					891:894	a Mini-Mental State Examination (MMSE) rate	852:894	a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year	852:928	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	3	48	theme	longitudinal	589:600	arg1	study					602:606	a longitudinal study	587:606	a longitudinal study of fish-derived, ω-3-supplemented patients with MCI	587:658	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	7	49	theme	fatty	1717:1721	arg1	acids					1723:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids	1580:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1580:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	49	theme	fatty	1717:1721	arg1	ApoEe3/e3					1519:1527	ApoEe3/e3	1519:1527	ApoEe3/e3	1519:1527	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	50	link	fish-derived	1347:1358	arg1	genes					1389:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	51	theme	M.	1706:1707	arg1	acids					1723:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids	1580:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1580:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	51	theme	M.	1706:1707	arg1	ApoEe3/e3					1519:1527	ApoEe3/e3	1519:1527	ApoEe3/e3	1519:1527	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	52	theme	kinase	758:763	arg1	PERK					785:788	PERK	785:788	PERK	785:788	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	52	theme	kinase	758:763	arg1	kinase					777:782	protein kinase RNA-like ER kinase	750:782	protein kinase RNA-like ER kinase (PERK) expression	750:800	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	53	from	ApoEe3/e3	1519:1527	arg1	rate					1501:1504	an improved MMSE rate	1484:1504	an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1484:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	2	54	theme	ω-3	393:395	arg1	mediator					397:404	the ω-3 mediator	389:404	the ω-3 mediator	389:404	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	2	54	theme	ω-3	393:395	arg1	D1					416:417	resolvin D1	407:417	resolvin D1	407:417	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	3	55	link	fish-derived	611:622	arg1	patients					642:649	fish-derived, ω-3-supplemented patients	611:649	fish-derived, ω-3-supplemented patients with MCI	611:658	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	1	56	contain	have	297:300	arg1	Macrophages					153:163	Macrophages	153:163	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI)	153:242	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	1	56	contain	have	297:300	arg2	resistance					306:315	low resistance	302:315	low resistance to apoptosis by Aβ	302:334	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	1	56	contain	have	297:300	arg1	Mϕs					166:168	Mϕs	166:168	Mϕs	166:168	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	1	57	theme	patients	174:181	arg1	Macrophages					153:163	Macrophages	153:163	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI)	153:242	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	1	57	theme	patients	174:181	arg1	Mϕs					166:168	Mϕs	166:168	Mϕs	166:168	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
28634213	7	58	theme	mild	1835:1838	arg1	impairment					1850:1859	mild cognitive impairment	1835:1859	mild cognitive impairment	1835:1859	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	0	59	theme	mild	126:129	arg1	impairment					141:150	mild cognitive impairment	126:150	mild cognitive impairment	126:150	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	60	theme	Aβ	1456:1457	arg1	clearance					1443:1451	immune clearance	1436:1451	immune clearance of Aβ	1436:1457	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	2	61	theme	patients	464:471	arg1	Mϕs					457:459	Mϕs	457:459	Mϕs of patients with MCI	457:480	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	5	62	dep	In	1065:1066	arg1	vitro					1068:1072	vitro	1068:1072	vitro	1068:1072	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	7	63	from	M.	1571:1572	arg1	rate					1501:1504	an improved MMSE rate	1484:1504	an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1484:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	64	theme	patients	1821:1828	arg1	phagocytosis					1790:1801	amyloid-β phagocytosis	1780:1801	amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment	1780:1859	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	3	65	theme	patients	642:649	arg1	study					602:606	a longitudinal study	587:606	a longitudinal study of fish-derived, ω-3-supplemented patients with MCI	587:658	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	3	66	theme	unfolded	508:515	arg1	UPR					535:537	UPR	535:537	UPR	535:537	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	3	66	theme	unfolded	508:515	arg1	response					525:532	the unfolded protein response	504:532	the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress	504:575	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	6	67	theme	glycosylation	1312:1324	arg1	enzymes					1326:1332	N-linked glycosylation enzymes	1303:1332	N-linked glycosylation enzymes	1303:1332	Augmented genes in the UPR signature included chaperones, lectins, foldases, and N-linked glycosylation enzymes.
28634213	4	68	from	patients	939:946	arg1	subgroup					965:972	the ApoEe3/e4 subgroup	951:972	the ApoEe3/e4 subgroup	951:972	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	69	theme	ER	774:775	arg1	PERK					785:788	PERK	785:788	PERK	785:788	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	69	theme	ER	774:775	arg1	kinase					777:782	protein kinase RNA-like ER kinase	750:782	protein kinase RNA-like ER kinase (PERK) expression	750:800	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	70	theme	change	1033:1038	arg1	rate					1025:1028	an MMSE rate	1017:1028	an MMSE rate of change of -3.2 points per year	1017:1062	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	5	71	theme	fish-derived	1094:1105	arg1	emulsion					1111:1118	fish-derived ω-3 emulsion	1094:1118	fish-derived ω-3 emulsion	1094:1118	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	5	72	link	fish-derived	1094:1105	arg1	emulsion					1111:1118	fish-derived ω-3 emulsion	1094:1118	fish-derived ω-3 emulsion	1094:1118	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	7	73	from	rate	1501:1504	arg1	acids					1723:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids	1580:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1580:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	73	from	rate	1501:1504	arg1	Lam					1575:1577	Lam	1575:1577	Lam	1575:1577	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	73	from	rate	1501:1504	arg1	H.					1568:1569	H.	1568:1569	H.	1568:1569	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	73	from	rate	1501:1504	arg1	ApoEe3/e3					1519:1527	ApoEe3/e3	1519:1527	ApoEe3/e3	1519:1527	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	73	from	rate	1501:1504	arg1	M.					1571:1572	M.	1571:1572	M.	1571:1572	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	6	74	from	genes	1232:1236	arg1	UPR					1245:1247	the UPR	1241:1247	the UPR	1241:1247	Augmented genes in the UPR signature included chaperones, lectins, foldases, and N-linked glycosylation enzymes.
28634213	7	75	theme	decrease	1399:1406	arg1	genes					1421:1425	decrease proapoptotic genes	1399:1425	decrease proapoptotic genes	1399:1425	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	76	theme	Mϕ	839:840	arg1	type					842:845	intermediate M1-M2 Mϕ type	820:845	intermediate M1-M2 Mϕ type	820:845	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	77	from	change	1509:1514	arg1	acids					1723:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids	1580:1727	L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1580:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	77	from	change	1509:1514	arg1	Lam					1575:1577	Lam	1575:1577	Lam	1575:1577	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	77	from	change	1509:1514	arg1	H.					1568:1569	H.	1568:1569	H.	1568:1569	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	77	from	change	1509:1514	arg1	ApoEe3/e3					1519:1527	ApoEe3/e3	1519:1527	ApoEe3/e3	1519:1527	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	77	from	change	1509:1514	arg1	M.					1571:1572	M.	1571:1572	M.	1571:1572	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	78	dep	acids	1723:1727	arg1	increase					1729:1736	increase	1729:1736	increase the unfolded protein response	1729:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	79	theme	unfolded	1742:1749	arg1	response					1759:1766	the unfolded protein response	1738:1766	the unfolded protein response	1738:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	5	80	theme	Mϕs	1087:1089	arg1	treatment					1074:1082	In vitro treatment	1065:1082	In vitro treatment of Mϕs by fish-derived ω-3 emulsion	1065:1118	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	7	81	theme	increase	1365:1372	arg1	genes					1389:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	0	82	theme	patients	112:119	arg1	phagocytosis					81:92	amyloid-β phagocytosis	71:92	amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment	71:150	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	83	theme	change	1509:1514	arg1	rate					1501:1504	an improved MMSE rate	1484:1504	an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1484:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	4	84	theme	intermediate	820:831	arg1	type					842:845	intermediate M1-M2 Mϕ type	820:845	intermediate M1-M2 Mϕ type	820:845	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	85	theme	M1-M2	833:837	arg1	type					842:845	intermediate M1-M2 Mϕ type	820:845	intermediate M1-M2 Mϕ type	820:845	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	0	86	theme	fatty	8:12	arg1	acids					14:18	Omega-3 fatty acids	0:18	Omega-3 fatty acids	0:18	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	3	87	with	patients	642:649	arg1	MCI					656:658	MCI	656:658	MCI	656:658	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	6	88	link	N-linked	1303:1310	arg1	enzymes					1326:1332	N-linked glycosylation enzymes	1303:1332	N-linked glycosylation enzymes	1303:1332	Augmented genes in the UPR signature included chaperones, lectins, foldases, and N-linked glycosylation enzymes.
28634213	5	89	theme	Aβ	1130:1131	arg1	phagocytosis					1133:1144	Aβ phagocytosis	1130:1144	Aβ phagocytosis	1130:1144	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	2	90	theme	fatty	345:349	arg1	ω-3s					358:361	ω-3s	358:361	ω-3s	358:361	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	2	90	theme	fatty	345:349	arg1	acids					351:355	Omega-3 fatty acids	337:355	Omega-3 fatty acids (ω-3s)	337:362	Omega-3 fatty acids (ω-3s) in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI.
28634213	4	91	dep	exhibited	725:733	arg1	whereas					931:937	whereas	931:937	whereas	931:937	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	7	92	theme	improved	1487:1494	arg1	rate					1501:1504	an improved MMSE rate	1484:1504	an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response	1484:1766	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	3	93	theme	reticulum	555:563	arg1	stress					570:575	endoplasmic reticulum (ER) stress	543:575	endoplasmic reticulum (ER) stress	543:575	We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI.
28634213	0	94	theme	unfolded	33:40	arg1	response					50:57	the unfolded protein response	29:57	the unfolded protein response	29:57	Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	7	95	theme	ω-3s	1360:1363	arg1	genes					1389:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	fish-derived ω-3s increase cytoprotective genes	1347:1393	In summary, fish-derived ω-3s increase cytoprotective genes and decrease proapoptotic genes, improve immune clearance of Aβ, and are associated with an improved MMSE rate of change in ApoEe3/e3 vs. ApoEe3/e4 patients.-Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment.
28634213	5	96	theme	In	1065:1066	arg1	treatment					1074:1082	In vitro treatment	1065:1082	In vitro treatment of Mϕs by fish-derived ω-3 emulsion	1065:1118	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	6	97	theme	Augmented	1222:1230	arg1	genes					1232:1236	Augmented genes	1222:1236	Augmented genes in the UPR	1222:1247	Augmented genes in the UPR signature included chaperones, lectins, foldases, and N-linked glycosylation enzymes.
28634213	4	98	theme	State	866:870	arg1	MMSE					885:888	MMSE	885:888	MMSE	885:888	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	98	theme	State	866:870	arg1	Examination					872:882	a Mini-Mental State Examination	852:882	a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year	852:928	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	5	99	theme	stress	1204:1209	arg1	signature					1211:1219	ER stress signature	1201:1219	ER stress signature	1201:1219	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	6	100	theme	N-linked	1303:1310	arg1	enzymes					1326:1332	N-linked glycosylation enzymes	1303:1332	N-linked glycosylation enzymes	1303:1332	Augmented genes in the UPR signature included chaperones, lectins, foldases, and N-linked glycosylation enzymes.
28634213	4	101	theme	points	914:919	arg1	change					899:904	change	899:904	change of +1.8 points	899:919	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	4	102	theme	apolipoprotein	677:690	arg1	subgroup					706:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	the apolipoprotein E (ApoE)e3/e3 subgroup	673:713	Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1.8 points per year, whereas patients in the ApoEe3/e4 subgroup showed individually divergent results with an MMSE rate of change of -3.2 points per year.
28634213	5	103	theme	RNA	1172:1174	arg1	signature					1176:1184	UPR RNA signature	1168:1184	UPR RNA signature	1168:1184	In vitro treatment of Mϕs by fish-derived ω-3 emulsion increased Aβ phagocytosis, PERK expression, and UPR RNA signature, and decreased ER stress signature.
28634213	1	104	theme	cognitive	217:225	arg1	impairment					227:236	mild cognitive impairment	212:236	mild cognitive impairment	212:236	Macrophages (Mϕs) of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ.
30054538	4	0	theme	PrPSc	874:878	arg1	particles					880:888	PrPSc particles	874:888	PrPSc particles	874:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	9	1	theme	PrPSc	1632:1636	arg1	surface					1638:1644	PrPSc surface	1632:1644	PrPSc surface	1632:1644	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	2	2	theme	time	274:277	arg1	correlations					279:290	space and time correlations	264:290	space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation	264:420	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	4	3	theme	current	664:670	arg1	study					672:676	The current study	660:676	The current study	660:676	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	2	4	theme	space	264:268	arg1	correlations					279:290	space and time correlations	264:290	space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation	264:420	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	1	5	theme	diseases	182:189	arg1	features					152:159	the obligatory pathogenic features	126:159	the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases	126:242	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	12	6	theme	inflammatory	2133:2144	arg1	response					2146:2153	inflammatory response	2133:2153	inflammatory response in microglia	2133:2166	The current study is the first to demonstrate that PrPSc can directly trigger inflammatory response in microglia.
30054538	3	7	theme	PrPSc	578:582	arg1	microglia					584:592	PrPSc microglia	578:592	PrPSc microglia	578:592	Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPSc microglia sense and respond to that drive microglia to inflammatory states.
30054538	9	8	theme	sialylation	1661:1671	arg1	levels					1651:1656	the levels	1647:1656	the levels of sialylation of PrPSc N-linked glycans	1647:1697	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	9	9	theme	PrPSc	1676:1680	arg1	glycans					1691:1697	PrPSc N-linked glycans	1676:1697	PrPSc N-linked glycans	1676:1697	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	10	10	theme	sialic	1782:1787	arg1	residues					1794:1801	sialic acid residues	1782:1801	sialic acid residues	1782:1801	Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc.
30054538	9	11	theme	glycans	1691:1697	arg1	sialylation					1661:1671	sialylation	1661:1671	sialylation of PrPSc N-linked glycans	1661:1697	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	7	12	theme	Synthase	1344:1351	arg1	oxide					1292:1296	nitric oxide	1285:1296	nitric oxide (NO)	1285:1301	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	12	theme	Synthase	1344:1351	arg1	TNFα					1274:1277	TNFα	1274:1277	TNFα	1274:1277	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	12	theme	Synthase	1344:1351	arg1	expression					1307:1316	expression	1307:1316	expression of inducible Nitric Oxide Synthase (iNOS)	1307:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	12	theme	Synthase	1344:1351	arg1	NO					1299:1300	NO	1299:1300	NO	1299:1300	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	12	theme	Synthase	1344:1351	arg1	IL6					1280:1282	IL6	1280:1282	IL6	1280:1282	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	13	13	theme	PrPSc	2272:2276	arg1	surface					2278:2284	PrPSc surface	2272:2284	PrPSc surface	2272:2284	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	7	14	theme	Nitric	1331:1336	arg1	iNOS					1354:1357	iNOS	1354:1357	iNOS	1354:1357	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	14	theme	Nitric	1331:1336	arg1	Synthase					1344:1351	inducible Nitric Oxide Synthase	1321:1351	inducible Nitric Oxide Synthase (iNOS)	1321:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	2	15	dep	disease-associated	314:331	arg1	pathogenic					334:343	pathogenic	334:343	pathogenic	334:343	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	6	16	theme	BV2	1028:1030	arg1	cells					1043:1047	BV2 microglial cells	1028:1047	BV2 microglial cells	1028:1047	BV2 microglial cells or primary microglia were cultured in the presence of purified 22L.
30054538	10	17	theme	residues	1794:1801	arg1	cleavage					1770:1777	Partial cleavage	1762:1777	Partial cleavage of sialic acid residues	1762:1801	Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc.
30054538	1	18	theme	pathogenic	141:150	arg1	features					152:159	the obligatory pathogenic features	126:159	the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases	126:242	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	9	19	theme	purified	1727:1734	arg1	PrPSc					1736:1740	purified PrPSc	1727:1740	purified PrPSc	1727:1740	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	8	20	theme	neuroblastoma	1461:1473	arg1	cells					1475:1479	neuroblastoma cells	1461:1479	neuroblastoma cells	1461:1479	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	12	21	theme	current	2059:2065	arg1	study					2067:2071	The current study	2055:2071	The current study	2055:2071	The current study is the first to demonstrate that PrPSc can directly trigger inflammatory response in microglia.
30054538	12	21	theme	current	2059:2065	arg1	first					2080:2084	first	2080:2084	first	2080:2084	The current study is the first to demonstrate that PrPSc can directly trigger inflammatory response in microglia.
30054538	11	22	theme	desialylated	1950:1961	arg1	PrPSc					1963:1967	partially desialylated PrPSc	1940:1967	partially desialylated PrPSc	1940:1967	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	13	23	theme	groups	2262:2267	arg1	important					2289:2297	important	2289:2297	important	2289:2297	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	13	23	theme	groups	2262:2267	arg1	nature					2235:2240	the chemical nature	2222:2240	the chemical nature of the carbohydrate groups on PrPSc surface	2222:2284	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	7	24	theme	proinflammatory	1202:1216	arg1	responses					1218:1226	proinflammatory responses	1202:1226	proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS)	1202:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	4	25	from	surface	863:869	arg1	nature					817:822	the nature	813:822	the nature of terminal carbohydrate groups on the surface of PrPSc particles	813:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	0	26	gly	sialylation	62:72	arg1	PrPSc					77:81	PrPSc	77:81	PrPSc	77:81	Inflammatory response of microglia to prions is controlled by sialylation of PrPSc.
30054538	8	27	theme	microglia	1494:1502	arg1	response					1504:1511	microglia response	1494:1511	microglia response	1494:1511	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	4	28	theme	microglia	783:791	arg1	response					793:800	microglia response	783:800	microglia response	783:800	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	5	29	theme	N2a	992:994	arg1	cells					996:1000	mouse-adapted prion strain 22L or neuroblastoma N2a cells	944:1000	cells	996:1000	PrPSc was purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L.
30054538	7	30	theme	expression	1307:1316	arg1	levels					1264:1269	the levels	1260:1269	the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS)	1260:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	11	31	gly	desialylated	1950:1961	arg1	PrPSc					1963:1967	partially desialylated PrPSc	1940:1967	partially desialylated PrPSc	1940:1967	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	4	32	theme	microglia	747:755	arg1	activation					733:742	activation	733:742	activation of microglia	733:755	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	0	33	theme	Inflammatory	0:11	arg1	response					13:20	Inflammatory response	0:20	Inflammatory response of microglia to prions	0:43	Inflammatory response of microglia to prions is controlled by sialylation of PrPSc.
30054538	5	34	theme	mouse-adapted	944:956	arg1	22L					971:973	mouse-adapted prion strain 22L or neuroblastoma N2a cells	944:1000	22L	971:973	PrPSc was purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L.
30054538	2	35	theme	prion	248:252	arg1	diseases					254:261	prion diseases	248:261	prion diseases	248:261	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	11	36	theme	Iκβα	1906:1909	arg1	degradation					1891:1901	transient degradation	1881:1901	transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc	1881:1967	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	7	37	theme	primary	1156:1162	arg1	microglia					1164:1172	primary microglia	1156:1172	primary microglia	1156:1172	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	13	38	theme	chemical	2226:2233	arg1	important					2289:2297	important	2289:2297	important	2289:2297	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	13	38	theme	chemical	2226:2233	arg1	nature					2235:2240	the chemical nature	2222:2240	the chemical nature of the carbohydrate groups on PrPSc surface	2222:2284	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	5	39	theme	strain	964:969	arg1	22L					971:973	mouse-adapted prion strain 22L or neuroblastoma N2a cells	944:1000	22L	971:973	PrPSc was purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L.
30054538	6	40	theme	primary	1052:1058	arg1	microglia					1060:1068	primary microglia	1052:1068	primary microglia	1052:1068	BV2 microglial cells or primary microglia were cultured in the presence of purified 22L.
30054538	8	41	theme	source	1535:1540	arg1	independent					1516:1526	independent	1516:1526	independent	1516:1526	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	10	42	theme	inflammatory	1826:1837	arg1	response					1839:1846	the inflammatory response	1822:1846	the inflammatory response of microglia to PrPSc	1822:1868	Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc.
30054538	7	43	theme	cells	1147:1151	arg1	exposure					1131:1138	exposure	1131:1138	exposure of BV2 cells or primary microglia to purified PrPSc	1131:1190	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	44	theme	nitric	1285:1290	arg1	oxide					1292:1296	nitric oxide	1285:1296	nitric oxide (NO)	1285:1301	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	44	theme	nitric	1285:1290	arg1	NO					1299:1300	NO	1299:1300	NO	1299:1300	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	8	45	theme	PrPSc	1545:1549	arg1	source					1535:1540	the source	1531:1540	the source of PrPSc	1531:1549	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	3	46	theme	inflammatory	639:650	arg1	states					652:657	inflammatory states	639:657	inflammatory states	639:657	Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPSc microglia sense and respond to that drive microglia to inflammatory states.
30054538	4	47	theme	carbohydrate	836:847	arg1	groups					849:854	terminal carbohydrate groups	827:854	terminal carbohydrate groups on the surface of PrPSc particles	827:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	13	48	theme	direct	2201:2206	arg1	evidence					2208:2215	direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation	2201:2323	direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation	2201:2323	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	7	49	theme	IL6	1280:1282	arg1	levels					1264:1269	the levels	1260:1269	the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS)	1260:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	8	50	theme	inflammatory	1386:1397	arg1	response					1399:1406	inflammatory response	1386:1406	inflammatory response	1386:1406	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	3	51	theme	microglia	490:498	arg1	activation					476:485	activation	476:485	activation of microglia	476:498	Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPSc microglia sense and respond to that drive microglia to inflammatory states.
30054538	11	52	theme	NFκB	1993:1996	arg1	pathway					2009:2015	canonical NFκB activation pathway	1983:2015	canonical NFκB activation pathway	1983:2015	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	7	53	theme	TNFα	1274:1277	arg1	levels					1264:1269	the levels	1260:1269	the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS)	1260:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	9	54	theme	carbohydrate	1607:1618	arg1	epitopes					1620:1627	carbohydrate epitopes	1607:1627	carbohydrate epitopes on PrPSc surface	1607:1644	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	6	55	theme	purified	1103:1110	arg1	22L					1112:1114	purified 22L	1103:1114	purified 22L	1103:1114	BV2 microglial cells or primary microglia were cultured in the presence of purified 22L.
30054538	2	56	theme	prion	357:361	arg1	protein					363:369	the prion protein	353:369	the prion protein	353:369	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	7	57	from	increase	1248:1255	arg1	levels					1264:1269	the levels	1260:1269	the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS)	1260:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	3	58	with	contact	527:533	arg1	PrPSc					540:544	PrPSc	540:544	PrPSc	540:544	Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPSc microglia sense and respond to that drive microglia to inflammatory states.
30054538	11	59	theme	activation	1998:2007	arg1	pathway					2009:2015	canonical NFκB activation pathway	1983:2015	canonical NFκB activation pathway	1983:2015	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	12	60	from	response	2146:2153	arg1	microglia					2158:2166	microglia	2158:2166	microglia	2158:2166	The current study is the first to demonstrate that PrPSc can directly trigger inflammatory response in microglia.
30054538	10	61	theme	Partial	1762:1768	arg1	cleavage					1770:1777	Partial cleavage	1762:1777	Partial cleavage of sialic acid residues	1762:1801	Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc.
30054538	4	62	theme	particles	880:888	arg1	surface					863:869	the surface	859:869	the surface of PrPSc particles	859:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	13	63	theme	carbohydrate	2249:2260	arg1	groups					2262:2267	the carbohydrate groups	2245:2267	the carbohydrate groups	2245:2267	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	11	64	theme	canonical	1983:1991	arg1	pathway					2009:2015	canonical NFκB activation pathway	1983:2015	canonical NFκB activation pathway	1983:2015	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	9	65	gly	sialylation	1661:1671	arg1	glycans					1691:1697	PrPSc N-linked glycans	1676:1697	PrPSc N-linked glycans	1676:1697	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	1	66	theme	neurodegenerative	164:180	arg1	Alzheimer					201:209	Alzheimer's	201:211	Alzheimer's	201:211	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	1	66	theme	neurodegenerative	164:180	arg1	diseases					182:189	neurodegenerative diseases	164:189	neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases	164:242	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	4	67	theme	groups	849:854	arg1	nature					817:822	the nature	813:822	the nature of terminal carbohydrate groups on the surface of PrPSc particles	813:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	2	68	theme	disease-associated	314:331	arg1	form					345:348	disease-associated, pathogenic form	314:348	disease-associated, pathogenic form of the prion protein or PrPSc	314:378	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	8	69	theme	similar	1366:1372	arg1	patterns					1374:1381	Very similar patterns	1361:1381	Very similar patterns of inflammatory response	1361:1406	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	3	70	theme	molecular	556:564	arg1	features					566:573	molecular features	556:573	molecular features of PrPSc microglia	556:592	Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPSc microglia sense and respond to that drive microglia to inflammatory states.
30054538	11	71	theme	inflammatory	2032:2043	arg1	response					2045:2052	inflammatory response	2032:2052	inflammatory response	2032:2052	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	10	72	theme	acid	1789:1792	arg1	residues					1794:1801	sialic acid residues	1782:1801	sialic acid residues	1782:1801	Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc.
30054538	13	73	theme	microglial	2303:2312	arg1	activation					2314:2323	microglial activation	2303:2323	microglial activation	2303:2323	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	9	74	theme	N-linked	1682:1689	arg1	glycans					1691:1697	PrPSc N-linked glycans	1676:1697	PrPSc N-linked glycans	1676:1697	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	3	75	theme	microglia	584:592	arg1	features					566:573	molecular features	556:573	molecular features of PrPSc microglia	556:592	Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPSc microglia sense and respond to that drive microglia to inflammatory states.
30054538	9	76	from	epitopes	1620:1627	arg1	surface					1638:1644	PrPSc surface	1632:1644	PrPSc surface	1632:1644	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	8	77	theme	mouse	1444:1448	arg1	brains					1450:1455	mouse brains	1444:1455	mouse brains	1444:1455	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	4	78	from	nature	817:822	arg1	surface					863:869	the surface	859:869	the surface of PrPSc particles	859:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	5	79	theme	mice	925:928	arg1	brains					915:920	brains	915:920	brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L	915:1025	PrPSc was purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L.
30054538	6	80	theme	microglial	1032:1041	arg1	cells					1043:1047	BV2 microglial cells	1028:1047	BV2 microglial cells	1028:1047	BV2 microglial cells or primary microglia were cultured in the presence of purified 22L.
30054538	7	81	theme	Oxide	1338:1342	arg1	iNOS					1354:1357	iNOS	1354:1357	iNOS	1354:1357	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	81	theme	Oxide	1338:1342	arg1	Synthase					1344:1351	inducible Nitric Oxide Synthase	1321:1351	inducible Nitric Oxide Synthase (iNOS)	1321:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	9	82	with	treatment	1714:1722	arg1	neuraminidase					1747:1759	neuraminidase	1747:1759	neuraminidase	1747:1759	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	1	83	theme	obligatory	130:139	arg1	features					152:159	the obligatory pathogenic features	126:159	the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases	126:242	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	7	84	theme	inducible	1321:1329	arg1	iNOS					1354:1357	iNOS	1354:1357	iNOS	1354:1357	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	84	theme	inducible	1321:1329	arg1	Synthase					1344:1351	inducible Nitric Oxide Synthase	1321:1351	inducible Nitric Oxide Synthase (iNOS)	1321:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	11	85	with	treatment	1925:1933	arg1	PrPSc					1963:1967	partially desialylated PrPSc	1940:1967	partially desialylated PrPSc	1940:1967	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	0	86	theme	PrPSc	77:81	arg1	sialylation					62:72	sialylation	62:72	sialylation of PrPSc	62:81	Inflammatory response of microglia to prions is controlled by sialylation of PrPSc.
30054538	1	87	theme	features	152:159	arg1	Neuroinflammation					84:100	Neuroinflammation	84:100	Neuroinflammation	84:100	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	1	87	theme	features	152:159	arg1	features					152:159	the obligatory pathogenic features	126:159	the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases	126:242	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	1	87	theme	features	152:159	arg1	one					119:121	one	119:121	one	119:121	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	9	88	theme	PrPSc	1736:1740	arg1	treatment					1714:1722	treatment	1714:1722	treatment of purified PrPSc with neuraminidase	1714:1759	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	7	89	theme	purified	1177:1184	arg1	PrPSc					1186:1190	purified PrPSc	1177:1190	purified PrPSc	1177:1190	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	5	90	theme	neuroblastoma	978:990	arg1	cells					996:1000	mouse-adapted prion strain 22L or neuroblastoma N2a cells	944:1000	cells	996:1000	PrPSc was purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L.
30054538	13	91	from	nature	2235:2240	arg1	surface					2278:2284	PrPSc surface	2272:2284	PrPSc surface	2272:2284	In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.
30054538	2	92	theme	microglial-mediated	384:402	arg1	neuroinflammation					404:420	microglial-mediated neuroinflammation	384:420	microglial-mediated neuroinflammation	384:420	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	7	93	theme	microglia	1164:1172	arg1	exposure					1131:1138	exposure	1131:1138	exposure of BV2 cells or primary microglia to purified PrPSc	1131:1190	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	4	94	from	groups	849:854	arg1	surface					863:869	the surface	859:869	the surface of PrPSc particles	859:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	2	95	theme	PrPSc	374:378	arg1	form					345:348	disease-associated, pathogenic form	314:348	disease-associated, pathogenic form of the prion protein or PrPSc	314:378	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	0	96	theme	microglia	25:33	arg1	response					13:20	Inflammatory response	0:20	Inflammatory response of microglia to prions	0:43	Inflammatory response of microglia to prions is controlled by sialylation of PrPSc.
30054538	5	97	theme	prion	958:962	arg1	22L					971:973	mouse-adapted prion strain 22L or neuroblastoma N2a cells	944:1000	22L	971:973	PrPSc was purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L.
30054538	7	98	theme	oxide	1292:1296	arg1	levels					1264:1269	the levels	1260:1269	the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS)	1260:1358	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	7	99	theme	BV2	1143:1145	arg1	cells					1147:1151	BV2 cells	1143:1151	BV2 cells	1143:1151	We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS).
30054538	9	100	theme	microglial	1572:1581	arg1	response					1583:1590	the microglial response	1568:1590	the microglial response	1568:1590	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	4	101	theme	terminal	827:834	arg1	groups					849:854	terminal carbohydrate groups	827:854	terminal carbohydrate groups on the surface of PrPSc particles	827:888	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	2	102	theme	form	345:348	arg1	deposition					300:309	deposition	300:309	deposition of disease-associated, pathogenic form of the prion protein or PrPSc	300:378	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	2	102	theme	form	345:348	arg1	neuroinflammation					404:420	microglial-mediated neuroinflammation	384:420	microglial-mediated neuroinflammation	384:420	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
30054538	10	103	theme	microglia	1851:1859	arg1	response					1839:1846	the inflammatory response	1822:1846	the inflammatory response of microglia to PrPSc	1822:1868	Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc.
30054538	4	104	theme	response	793:800	arg1	degree					773:778	the degree	769:778	the degree of microglia response	769:800	The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles.
30054538	9	105	link	N-linked	1682:1689	arg1	glycans					1691:1697	PrPSc N-linked glycans	1676:1697	PrPSc N-linked glycans	1676:1697	To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase.
30054538	1	106	theme	prion	229:233	arg1	diseases					235:242	prion diseases	229:242	prion diseases	229:242	Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer's, Parkinson's or prion diseases.
30054538	6	107	theme	22L	1112:1114	arg1	presence					1091:1098	the presence	1087:1098	the presence of purified 22L	1087:1114	BV2 microglial cells or primary microglia were cultured in the presence of purified 22L.
30054538	11	108	theme	transient	1881:1889	arg1	degradation					1891:1901	transient degradation	1881:1901	transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc	1881:1967	Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response.
30054538	8	109	theme	response	1399:1406	arg1	patterns					1374:1381	Very similar patterns	1361:1381	Very similar patterns of inflammatory response	1361:1406	Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc.
30054538	2	110	theme	protein	363:369	arg1	form					345:348	disease-associated, pathogenic form	314:348	disease-associated, pathogenic form of the prion protein or PrPSc	314:378	In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established.
31012303	2	0	theme	primary	289:295	arg1	hepatotoxicity					327:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	2	0	theme	primary	289:295	arg1	formation					222:230	The formation	218:230	The formation of PA-derived pyrrole-protein adducts	218:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	5	1	theme	adducts	1312:1318	arg1	amount					1291:1296	the amount	1287:1296	the amount of pyrrole-Hb adducts	1287:1318	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	1	theme	adducts	1312:1318	arg1	adducts					1312:1318	pyrrole-Hb adducts	1301:1318	pyrrole-Hb adducts	1301:1318	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	1	theme	adducts	1312:1318	arg1	higher					1338:1343	higher	1338:1343	higher	1338:1343	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	8	2	theme	longer	1990:1995	arg1	span					2002:2005	longer life span	1990:2005	longer life span	1990:2005	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	8	3	theme	AgNO3	1816:1820	arg1	method					1837:1842	the AgNO3 derivatization method	1812:1842	the AgNO3 derivatization method	1812:1842	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	3	4	dep	apply	522:526	arg1	ii					518:519	ii	518:519	ii	518:519	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	2	5	theme	initiating	305:314	arg1	hepatotoxicity					327:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	2	5	theme	initiating	305:314	arg1	formation					222:230	The formation	218:230	The formation of PA-derived pyrrole-protein adducts	218:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	1	6	theme	flowering	200:208	arg1	plants					210:215	flowering plants	200:215	flowering plants	200:215	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	4	7	theme	pyrrole-amino	667:679	arg1	conjugates					686:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	7	theme	pyrrole-amino	667:679	arg1	9-histidine-DHP					792:806	9-histidine-DHP	792:806	9-histidine-DHP	792:806	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	7	theme	pyrrole-amino	667:679	arg1	-cysteine					761:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine	698:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP)	698:786	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	3	8	from	tendency	568:575	arg1	samples					654:660	blood samples	648:660	blood samples	648:660	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	6	9	theme	adducts	1426:1432	arg1	half-life					1402:1410	elimination half-life	1390:1410	elimination half-life of pyrrole-Hb adducts	1390:1432	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	4	10	theme	adducts	955:961	arg1	N-linkage					926:934	N-linkage	926:934	N-linkage	926:934	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	10	theme	adducts	955:961	arg1	S-linkage					912:920	both S-linkage	907:920	both S-linkage	907:920	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	11	theme	DHP	757:759	arg1	conjugates					686:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	11	theme	DHP	757:759	arg1	7-cysteine-DHP					772:785	7-cysteine-DHP	772:785	7-cysteine-DHP	772:785	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	11	theme	DHP	757:759	arg1	-cysteine					761:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine	698:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP)	698:786	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	8	12	theme	better	2018:2023	arg1	biomarker					2025:2033	a better biomarker	2016:2033	a better biomarker of PA exposure	2016:2048	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	8	12	theme	better	2018:2023	arg1	adducts					1949:1955	pyrrole-Hb adducts	1938:1955	pyrrole-Hb adducts with remarkably higher level and longer life span	1938:2005	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	5	13	theme	blood	1164:1168	arg1	fractions					1178:1186	monocrotaline-treated rat blood protein fractions	1138:1186	monocrotaline-treated rat blood protein fractions	1138:1186	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	13	theme	blood	1164:1168	arg1	plasma					1216:1221	plasma	1216:1221	plasma	1216:1221	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	13	theme	blood	1164:1168	arg1	fractions					1261:1269	plasma residual protein fractions	1237:1269	plasma residual protein fractions	1237:1269	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	13	theme	blood	1164:1168	arg1	albumin					1224:1230	albumin	1224:1230	albumin	1224:1230	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	13	theme	blood	1164:1168	arg1	hemoglobin					1199:1208	hemoglobin	1199:1208	hemoglobin (Hb)	1199:1213	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	3	14	theme	elimination	597:607	arg1	kinetics					609:616	elimination kinetics	597:616	elimination kinetics	597:616	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	6	15	theme	elimination	1390:1400	arg1	half-life					1402:1410	elimination half-life	1390:1410	elimination half-life of pyrrole-Hb adducts	1390:1432	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	3	16	theme	blood	648:652	arg1	samples					654:660	blood samples	648:660	blood samples	648:660	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	5	17	theme	AgNO3	994:998	arg1	derivatization					1000:1013	precolumn AgNO3 derivatization	984:1013	precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis	984:1094	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	2	18	link	PA-derived	235:244	arg1	adducts					262:268	PA-derived pyrrole-protein adducts	235:268	PA-derived pyrrole-protein adducts	235:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	8	19	theme	exposure	2041:2048	arg1	biomarker					2025:2033	a better biomarker	2016:2033	a better biomarker of PA exposure	2016:2048	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	8	19	theme	exposure	2041:2048	arg1	adducts					1949:1955	pyrrole-Hb adducts	1938:1955	pyrrole-Hb adducts with remarkably higher level and longer life span	1938:2005	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	3	20	theme	adducts	637:643	arg1	kinetics					609:616	elimination kinetics	597:616	elimination kinetics	597:616	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	3	20	theme	adducts	637:643	arg1	dose-response					578:590	dose-response	578:590	dose-response	578:590	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	3	20	theme	adducts	637:643	arg1	tendency					568:575	the binding tendency	556:575	the binding tendency	556:575	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	4	21	theme	H-pyrrolizine	742:754	arg1	conjugates					686:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	21	theme	H-pyrrolizine	742:754	arg1	7-cysteine-DHP					772:785	7-cysteine-DHP	772:785	7-cysteine-DHP	772:785	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	21	theme	H-pyrrolizine	742:754	arg1	-cysteine					761:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine	698:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP)	698:786	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	0	22	theme	Alkaloid	81:88	arg1	Exposure					90:97	Pyrrolizidine Alkaloid Exposure	67:97	Pyrrolizidine Alkaloid Exposure	67:97	Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.
31012303	8	23	theme	pyrrole-protein	1890:1904	arg1	adducts					1906:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	7	24	theme	pyrrole-protein	1663:1677	arg1	adducts					1679:1685	pyrrole-protein adducts	1663:1685	pyrrole-protein adducts in blood cells	1663:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	5	25	theme	plasma	1362:1367	arg1	fractions					1369:1377	all plasma fractions	1358:1377	all plasma fractions	1358:1377	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	6	26	theme	pyrrole-protein	1469:1483	arg1	adducts					1485:1491	pyrrole-protein adducts	1469:1491	pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days)	1469:1537	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	3	27	theme	binding	560:566	arg1	tendency					568:575	the binding tendency	556:575	the binding tendency	556:575	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	5	28	theme	chromatography/mass	1054:1072	arg1	spectrometry					1074:1085	ultra-high-pressure liquid chromatography/mass spectrometry	1027:1085	ultra-high-pressure liquid chromatography/mass spectrometry analysis	1027:1094	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	3	29	from	adducts	637:643	arg1	samples					654:660	blood samples	648:660	blood samples	648:660	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	6	30	from	adducts	1485:1491	arg1	days					1533:1536	12.08 vs 2.54-2.93 days	1514:1536	12.08 vs 2.54-2.93 days	1514:1536	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	6	30	from	adducts	1485:1491	arg1	fractions					1503:1511	plasma fractions	1496:1511	plasma fractions (12.08 vs 2.54-2.93 days)	1496:1537	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	8	31	with	adducts	1949:1955	arg1	span					2002:2005	longer life span	1990:2005	longer life span	1990:2005	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	8	31	with	adducts	1949:1955	arg1	level					1980:1984	remarkably higher level	1962:1984	remarkably higher level	1962:1984	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	3	32	theme	acidified	443:451	arg1	AgNO3					463:467	acidified ethanolic AgNO3	443:467	acidified ethanolic AgNO3	443:467	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	0	33	theme	Pyrrole-Hemoglobin	0:17	arg1	Adducts					19:25	Pyrrole-Hemoglobin Adducts	0:25	Pyrrole-Hemoglobin Adducts	0:25	Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.
31012303	8	34	theme	pyrrole-Hb	1938:1947	arg1	biomarker					2025:2033	a better biomarker	2016:2033	a better biomarker of PA exposure	2016:2048	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	8	34	theme	pyrrole-Hb	1938:1947	arg1	adducts					1949:1955	pyrrole-Hb adducts	1938:1955	pyrrole-Hb adducts with remarkably higher level and longer life span	1938:2005	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	1	35	theme	Pyrrolizidine	100:112	arg1	phytotoxins					154:164	naturally occurring phytotoxins	134:164	naturally occurring phytotoxins widely distributed in about 3% of flowering plants	134:215	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	1	35	theme	Pyrrolizidine	100:112	arg1	PAs					125:127	PAs	125:127	PAs	125:127	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	1	35	theme	Pyrrolizidine	100:112	arg1	alkaloids					114:122	Pyrrolizidine alkaloids	100:122	Pyrrolizidine alkaloids (PAs)	100:128	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	2	36	theme	adducts	262:268	arg1	hepatotoxicity					327:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	2	36	theme	adducts	262:268	arg1	formation					222:230	The formation	218:230	The formation of PA-derived pyrrole-protein adducts	218:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	7	37	from	amount	1653:1658	arg1	cells					1696:1700	blood cells	1690:1700	blood cells	1690:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	5	38	theme	ultra-high-pressure	1027:1045	arg1	spectrometry					1074:1085	ultra-high-pressure liquid chromatography/mass spectrometry	1027:1085	ultra-high-pressure liquid chromatography/mass spectrometry analysis	1027:1094	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	4	39	theme	acidified	855:863	arg1	derivatization					881:894	acidified ethanolic AgNO3 derivatization	855:894	acidified ethanolic AgNO3 derivatization	855:894	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	5	40	theme	residual	1244:1251	arg1	fractions					1261:1269	plasma residual protein fractions	1237:1269	plasma residual protein fractions	1237:1269	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	3	41	theme	established	403:413	arg1	method					430:435	our previous established derivatization method	390:435	our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts	390:511	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	4	42	theme	AgNO3	875:879	arg1	derivatization					881:894	acidified ethanolic AgNO3 derivatization	855:894	acidified ethanolic AgNO3 derivatization	855:894	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	0	43	theme	Potential	44:52	arg1	Biomarker					54:62	a More Feasible Potential Biomarker	28:62	a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure	28:97	Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.
31012303	7	44	theme	liver	1612:1616	arg1	patients					1625:1632	five PA-induced liver injury patients	1596:1632	five PA-induced liver injury patients	1596:1632	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	5	45	theme	rat	1160:1162	arg1	fractions					1178:1186	monocrotaline-treated rat blood protein fractions	1138:1186	monocrotaline-treated rat blood protein fractions	1138:1186	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	45	theme	rat	1160:1162	arg1	plasma					1216:1221	plasma	1216:1221	plasma	1216:1221	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	45	theme	rat	1160:1162	arg1	fractions					1261:1269	plasma residual protein fractions	1237:1269	plasma residual protein fractions	1237:1269	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	45	theme	rat	1160:1162	arg1	albumin					1224:1230	albumin	1224:1230	albumin	1224:1230	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	45	theme	rat	1160:1162	arg1	hemoglobin					1199:1208	hemoglobin	1199:1208	hemoglobin (Hb)	1199:1213	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	2	46	theme	pyrrole-protein	246:260	arg1	adducts					262:268	PA-derived pyrrole-protein adducts	235:268	PA-derived pyrrole-protein adducts	235:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	3	47	theme	adducts	505:511	arg1	analysis					477:484	the analysis	473:484	the analysis of pyrrole-protein adducts	473:511	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	7	48	from	cells	1696:1700	arg1	higher					1722:1727	higher	1722:1727	higher	1722:1727	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	7	48	from	cells	1696:1700	arg1	amount					1653:1658	the amount	1649:1658	the amount of pyrrole-protein adducts in blood cells	1649:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	7	48	from	cells	1696:1700	arg1	adducts					1679:1685	pyrrole-protein adducts	1663:1685	pyrrole-protein adducts in blood cells	1663:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	5	49	theme	pyrrole-protein	1111:1125	arg1	adducts					1127:1133	pyrrole-protein adducts	1111:1133	pyrrole-protein adducts	1111:1133	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	6	50	theme	plasma	1496:1501	arg1	days					1533:1536	12.08 vs 2.54-2.93 days	1514:1536	12.08 vs 2.54-2.93 days	1514:1536	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	6	50	theme	plasma	1496:1501	arg1	fractions					1503:1511	plasma fractions	1496:1511	plasma fractions (12.08 vs 2.54-2.93 days)	1496:1537	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	7	51	theme	blood	1568:1572	arg1	samples					1574:1580	blood samples	1568:1580	blood samples obtained from five PA-induced liver injury patients	1568:1632	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	3	52	from	samples	654:660	arg1	kinetics					609:616	elimination kinetics	597:616	elimination kinetics	597:616	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	3	52	from	samples	654:660	arg1	dose-response					578:590	dose-response	578:590	dose-response	578:590	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	3	52	from	samples	654:660	arg1	tendency					568:575	the binding tendency	556:575	the binding tendency	556:575	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	8	53	theme	higher	1973:1978	arg1	level					1980:1984	remarkably higher level	1962:1984	remarkably higher level	1962:1984	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	2	54	theme	trigger	297:303	arg1	hepatotoxicity					327:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	2	54	theme	trigger	297:303	arg1	formation					222:230	The formation	218:230	The formation of PA-derived pyrrole-protein adducts	218:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	5	55	theme	pyrrole-Hb	1301:1310	arg1	adducts					1312:1318	pyrrole-Hb adducts	1301:1318	pyrrole-Hb adducts	1301:1318	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	8	56	theme	first	1786:1790	arg1	time					1792:1795	the first time	1782:1795	the first time	1782:1795	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	4	57	theme	acid	681:684	arg1	conjugates					686:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	57	theme	acid	681:684	arg1	9-histidine-DHP					792:806	9-histidine-DHP	792:806	9-histidine-DHP	792:806	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	57	theme	acid	681:684	arg1	-cysteine					761:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine	698:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP)	698:786	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	8	58	theme	life	1997:2000	arg1	span					2002:2005	longer life span	1990:2005	longer life span	1990:2005	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	2	59	theme	PA-induced	316:325	arg1	hepatotoxicity					327:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	a primary trigger initiating PA-induced hepatotoxicity	287:340	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	2	59	theme	PA-induced	316:325	arg1	formation					222:230	The formation	218:230	The formation of PA-derived pyrrole-protein adducts	218:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	8	60	link	N-linked	1881:1888	arg1	adducts					1906:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	2	61	theme	PA-derived	235:244	arg1	adducts					262:268	PA-derived pyrrole-protein adducts	235:268	PA-derived pyrrole-protein adducts	235:268	The formation of PA-derived pyrrole-protein adducts is considered as a primary trigger initiating PA-induced hepatotoxicity.
31012303	4	62	used	used	830:833	arg2	-cysteine					761:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine	698:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP)	698:786	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	62	used	used	830:833	arg2	conjugates					686:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	62	used	used	830:833	arg2	9-histidine-DHP					792:806	9-histidine-DHP	792:806	9-histidine-DHP	792:806	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	1	63	theme	plants	210:215	arg1	%					195:195	about 3%	188:195	about 3% of flowering plants	188:215	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	1	63	theme	plants	210:215	arg1	plants					210:215	flowering plants	200:215	flowering plants	200:215	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	6	64	theme	pyrrole-Hb	1415:1424	arg1	adducts					1426:1432	pyrrole-Hb adducts	1415:1432	pyrrole-Hb adducts	1415:1432	Moreover, elimination half-life of pyrrole-Hb adducts was also significantly longer than pyrrole-protein adducts in plasma fractions (12.08 vs 2.54-2.93 days).
31012303	4	65	theme	pyrrole-protein	939:953	arg1	adducts					955:961	pyrrole-protein adducts	939:961	pyrrole-protein adducts	939:961	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	8	66	used	used	1853:1856	arg2	method					1837:1842	the AgNO3 derivatization method	1812:1842	the AgNO3 derivatization method	1812:1842	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	8	67	theme	PA	2038:2039	arg1	exposure					2041:2048	PA exposure	2038:2048	PA exposure	2038:2048	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	5	68	theme	protein	1170:1176	arg1	fractions					1178:1186	monocrotaline-treated rat blood protein fractions	1138:1186	monocrotaline-treated rat blood protein fractions	1138:1186	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	68	theme	protein	1170:1176	arg1	plasma					1216:1221	plasma	1216:1221	plasma	1216:1221	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	68	theme	protein	1170:1176	arg1	fractions					1261:1269	plasma residual protein fractions	1237:1269	plasma residual protein fractions	1237:1269	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	68	theme	protein	1170:1176	arg1	albumin					1224:1230	albumin	1224:1230	albumin	1224:1230	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	68	theme	protein	1170:1176	arg1	hemoglobin					1199:1208	hemoglobin	1199:1208	hemoglobin (Hb)	1199:1213	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	69	theme	precolumn	984:992	arg1	derivatization					1000:1013	precolumn AgNO3 derivatization	984:1013	precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis	984:1094	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	7	70	theme	blood	1690:1694	arg1	cells					1696:1700	blood cells	1690:1700	blood cells	1690:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	3	71	from	dose-response	578:590	arg1	samples					654:660	blood samples	648:660	blood samples	648:660	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	0	72	theme	Pyrrolizidine	67:79	arg1	Exposure					90:97	Pyrrolizidine Alkaloid Exposure	67:97	Pyrrolizidine Alkaloid Exposure	67:97	Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.
31012303	3	73	theme	pyrrole-protein	621:635	arg1	adducts					637:643	pyrrole-protein adducts	621:643	pyrrole-protein adducts in blood samples	621:660	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	1	74	theme	occurring	144:152	arg1	phytotoxins					154:164	naturally occurring phytotoxins	134:164	naturally occurring phytotoxins widely distributed in about 3% of flowering plants	134:215	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	1	74	theme	occurring	144:152	arg1	alkaloids					114:122	Pyrrolizidine alkaloids	100:122	Pyrrolizidine alkaloids (PAs)	100:128	Pyrrolizidine alkaloids (PAs) are naturally occurring phytotoxins widely distributed in about 3% of flowering plants.
31012303	7	75	theme	adducts	1679:1685	arg1	higher					1722:1727	higher	1722:1727	higher	1722:1727	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	7	75	theme	adducts	1679:1685	arg1	amount					1653:1658	the amount	1649:1658	the amount of pyrrole-protein adducts in blood cells	1649:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	7	75	theme	adducts	1679:1685	arg1	adducts					1679:1685	pyrrole-protein adducts	1663:1685	pyrrole-protein adducts in blood cells	1663:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	4	76	theme	±	699:699	arg1	conjugates					686:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	76	theme	±	699:699	arg1	7-cysteine-DHP					772:785	7-cysteine-DHP	772:785	7-cysteine-DHP	772:785	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	76	theme	±	699:699	arg1	-cysteine					761:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine	698:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP)	698:786	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	0	77	theme	Exposure	90:97	arg1	Biomarker					54:62	a More Feasible Potential Biomarker	28:62	a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure	28:97	Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.
31012303	8	78	theme	S-	1874:1875	arg1	adducts					1906:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	3	79	theme	present	347:353	arg1	study					355:359	The present study	343:359	The present study	343:359	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	3	80	dep	validate	381:388	arg1	i					370:370	i	370:370	i	370:370	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	4	81	theme	-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5	701:740	arg1	conjugates					686:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates	663:695	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	81	theme	-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5	701:740	arg1	7-cysteine-DHP					772:785	7-cysteine-DHP	772:785	7-cysteine-DHP	772:785	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	4	81	theme	-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5	701:740	arg1	-cysteine					761:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine	698:769	(±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP)	698:786	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	5	82	theme	plasma	1237:1242	arg1	fractions					1261:1269	plasma residual protein fractions	1237:1269	plasma residual protein fractions	1237:1269	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	8	83	theme	N-linked	1881:1888	arg1	adducts					1906:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	both S- and N-linked pyrrole-protein adducts	1869:1912	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	5	84	theme	liquid	1047:1052	arg1	spectrometry					1074:1085	ultra-high-pressure liquid chromatography/mass spectrometry	1027:1085	ultra-high-pressure liquid chromatography/mass spectrometry analysis	1027:1094	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	85	theme	spectrometry	1074:1085	arg1	analysis					1087:1094	ultra-high-pressure liquid chromatography/mass spectrometry analysis	1027:1094	ultra-high-pressure liquid chromatography/mass spectrometry analysis	1027:1094	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	3	86	theme	previous	394:401	arg1	method					430:435	our previous established derivatization method	390:435	our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts	390:511	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	3	87	theme	ethanolic	453:461	arg1	AgNO3					463:467	acidified ethanolic AgNO3	443:467	acidified ethanolic AgNO3	443:467	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	8	88	theme	derivatization	1822:1835	arg1	method					1837:1842	the AgNO3 derivatization method	1812:1842	the AgNO3 derivatization method	1812:1842	In conclusion, our findings for the first time confirmed that the AgNO3 derivatization method could be used to measure both S- and N-linked pyrrole-protein adducts and also suggested that pyrrole-Hb adducts with remarkably higher level and longer life span could be a better biomarker of PA exposure.
31012303	3	89	from	kinetics	609:616	arg1	samples					654:660	blood samples	648:660	blood samples	648:660	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	3	90	theme	pyrrole-protein	489:503	arg1	adducts					505:511	pyrrole-protein adducts	489:511	pyrrole-protein adducts	489:511	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	0	91	theme	Feasible	35:42	arg1	Biomarker					54:62	a More Feasible Potential Biomarker	28:62	a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure	28:97	Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.
31012303	0	92	dep	Biomarker	54:62	arg1	Adducts					19:25	Pyrrole-Hemoglobin Adducts	0:25	Pyrrole-Hemoglobin Adducts	0:25	Pyrrole-Hemoglobin Adducts, a More Feasible Potential Biomarker of Pyrrolizidine Alkaloid Exposure.
31012303	5	93	theme	protein	1253:1259	arg1	fractions					1261:1269	plasma residual protein fractions	1237:1269	plasma residual protein fractions	1237:1269	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	7	94	from	adducts	1679:1685	arg1	cells					1696:1700	blood cells	1690:1700	blood cells	1690:1700	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	5	95	theme	monocrotaline-treated	1138:1158	arg1	fractions					1178:1186	monocrotaline-treated rat blood protein fractions	1138:1186	monocrotaline-treated rat blood protein fractions	1138:1186	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	95	theme	monocrotaline-treated	1138:1158	arg1	plasma					1216:1221	plasma	1216:1221	plasma	1216:1221	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	95	theme	monocrotaline-treated	1138:1158	arg1	fractions					1261:1269	plasma residual protein fractions	1237:1269	plasma residual protein fractions	1237:1269	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	95	theme	monocrotaline-treated	1138:1158	arg1	albumin					1224:1230	albumin	1224:1230	albumin	1224:1230	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	5	95	theme	monocrotaline-treated	1138:1158	arg1	hemoglobin					1199:1208	hemoglobin	1199:1208	hemoglobin (Hb)	1199:1213	Subsequently, using precolumn AgNO3 derivatization followed by ultra-high-pressure liquid chromatography/mass spectrometry analysis, we quantified pyrrole-protein adducts in monocrotaline-treated rat blood protein fractions, including hemoglobin (Hb), plasma, albumin, and plasma residual protein fractions, and found that the amount of pyrrole-Hb adducts was significantly higher than that in all plasma fractions.
31012303	3	96	theme	derivatization	415:428	arg1	method					430:435	our previous established derivatization method	390:435	our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts	390:511	The present study aims to (i) further validate our previous established derivatization method using acidified ethanolic AgNO3 for the analysis of pyrrole-protein adducts and (ii) apply this method to characterize the binding tendency, dose-response, and elimination kinetics of pyrrole-protein adducts in blood samples.
31012303	4	97	theme	ethanolic	865:873	arg1	derivatization					881:894	acidified ethanolic AgNO3 derivatization	855:894	acidified ethanolic AgNO3 derivatization	855:894	Two pyrrole-amino acid conjugates, (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-pyrrolizine (DHP)-cysteine (7-cysteine-DHP) and 9-histidine-DHP, were synthesized and used to demonstrate that acidified ethanolic AgNO3 derivatization can cleave both S-linkage and N-linkage of pyrrole-protein adducts.
31012303	7	98	theme	injury	1618:1623	arg1	patients					1625:1632	five PA-induced liver injury patients	1596:1632	five PA-induced liver injury patients	1596:1632	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
31012303	7	99	theme	PA-induced	1601:1610	arg1	patients					1625:1632	five PA-induced liver injury patients	1596:1632	five PA-induced liver injury patients	1596:1632	In addition, we also tested blood samples obtained from five PA-induced liver injury patients and found that the amount of pyrrole-protein adducts in blood cells was also remarkably higher than that in plasma.
30944176	9	0	from	attenuation	1511:1521	arg1	mice.IMPORTANCE					1550:1564	mice.IMPORTANCE	1550:1564	mice.IMPORTANCE	1550:1564	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	1	dep	lectins	1289:1295	arg1	DC-SIGN					1377:1383	DC-SIGN	1377:1383	DC-SIGN	1377:1383	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	1	dep	lectins	1289:1295	arg1	DC-SIGN-related					1389:1403	DC-SIGN-related	1389:1403	DC-SIGN-related	1389:1403	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	1	dep	lectins	1289:1295	arg1	nonintegrin					1364:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin	1297:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)	1297:1384	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	11	2	theme	many	1952:1955	arg1	strains					1973:1979	many historical ZIKV strains	1952:1979	many historical ZIKV strains	1952:1979	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	10	3	theme	historical	1830:1839	arg1	strains					1846:1852	historical ZIKV strains	1830:1852	historical ZIKV strains	1830:1852	One contributing factor could be genetic differences between contemporary ZIKV strains and historical ZIKV strains.
30944176	12	4	from	virulence	2109:2117	arg1	mice					2122:2125	mice	2122:2125	mice	2122:2125	We generated nonglycosylated ZIKV mutants from contemporary and historical strains and evaluated their virulence in mice.
30944176	14	5	theme	ZIKV	2305:2308	arg1	pathogenesis					2310:2321	ZIKV pathogenesis	2305:2321	ZIKV pathogenesis	2305:2321	Our studies suggest that envelope protein glycosylation contributes to ZIKV pathogenesis, possibly by facilitating attachment to and infection of lectin-expressing leukocytes.
30944176	4	6	from	site	517:520	arg1	N154					551:554	N154	551:554	N154	551:554	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	6	from	site	517:520	arg1	protein					542:548	the envelope (E) protein	525:548	the envelope (E) protein (N154)	525:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	12	7	theme	historical	2070:2079	arg1	strains					2081:2087	contemporary and historical strains	2053:2087	contemporary and historical strains	2053:2087	We generated nonglycosylated ZIKV mutants from contemporary and historical strains and evaluated their virulence in mice.
30944176	11	8	from	outbreaks	1880:1888	arg1	protein					1914:1920	a viral envelope protein	1897:1920	a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation	1897:2003	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	11	8	from	outbreaks	1880:1888	arg1	isolates					1859:1866	All isolates	1855:1866	All isolates from recent outbreaks	1855:1888	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	9	9	theme	nonglycosylated	1526:1540	arg1	ZIKV					1542:1545	nonglycosylated ZIKV	1526:1545	nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks	1526:1736	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	14	10	theme	protein	2268:2274	arg1	glycosylation					2276:2288	envelope protein glycosylation	2259:2288	envelope protein glycosylation	2259:2288	Our studies suggest that envelope protein glycosylation contributes to ZIKV pathogenesis, possibly by facilitating attachment to and infection of lectin-expressing leukocytes.
30944176	5	11	theme	ZIKV	691:694	arg1	pathogenesis					696:707	ZIKV pathogenesis	691:707	ZIKV pathogenesis	691:707	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	4	12	theme	ZIKV	470:473	arg1	site					517:520	an N-linked glycosylation site	491:520	an N-linked glycosylation site in the envelope (E) protein (N154)	491:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	12	theme	ZIKV	470:473	arg1	isolates					475:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	11	13	theme	ZIKV	1968:1971	arg1	strains					1973:1979	many historical ZIKV strains	1952:1979	many historical ZIKV strains	1952:1979	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	11	14	theme	envelope	1905:1912	arg1	isolates					1859:1866	All isolates	1855:1866	All isolates from recent outbreaks	1855:1888	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	11	14	theme	envelope	1905:1912	arg1	protein					1914:1920	a viral envelope protein	1897:1920	a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation	1897:2003	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	12	15	theme	contemporary	2053:2064	arg1	strains					2081:2087	contemporary and historical strains	2053:2087	contemporary and historical strains	2053:2087	We generated nonglycosylated ZIKV mutants from contemporary and historical strains and evaluated their virulence in mice.
30944176	3	16	theme	ZIKV	323:326	arg1	infection					328:336	ZIKV infection	323:336	ZIKV infection	323:336	These outcomes were not associated with ZIKV infection prior to 2013, raising the possibility that viral genetic changes could contribute to new clinical manifestations.
30944176	5	17	theme	E	664:664	arg1	glycosylation					674:686	E protein glycosylation	664:686	E protein glycosylation	664:686	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	13	18	theme	viral	2201:2205	arg1	loads					2207:2211	lower viral loads	2195:2211	lower viral loads	2195:2211	We found that nonglycosylated viruses were attenuated and produced lower viral loads in serum and brains.
30944176	2	19	theme	congenital	228:237	arg1	syndrome					244:251	congenital Zika syndrome	228:251	congenital Zika syndrome	228:251	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	2	19	theme	congenital	228:237	arg1	malformations					213:225	neurodevelopmental malformations	194:225	neurodevelopmental malformations (congenital Zika syndrome)	194:252	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	4	20	link	N-linked	494:501	arg1	site					517:520	an N-linked glycosylation site	491:520	an N-linked glycosylation site in the envelope (E) protein (N154)	491:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	20	link	N-linked	494:501	arg1	isolates					475:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	11	21	gly	glycosylated	1930:1941	arg1	isolates					1859:1866	All isolates	1855:1866	All isolates from recent outbreaks	1855:1888	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	11	21	gly	glycosylated	1930:1941	arg1	protein					1914:1920	a viral envelope protein	1897:1920	a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation	1897:2003	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	5	22	theme	glycosylation	674:686	arg1	role					656:659	the role	652:659	the role of E protein glycosylation in ZIKV pathogenesis	652:707	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	13	23	gly	nonglycosylated	2142:2156	arg1	viruses					2158:2164	nonglycosylated viruses	2142:2164	nonglycosylated viruses	2142:2164	We found that nonglycosylated viruses were attenuated and produced lower viral loads in serum and brains.
30944176	12	24	gly	nonglycosylated	2019:2033	arg1	mutants					2040:2046	nonglycosylated ZIKV mutants	2019:2046	nonglycosylated ZIKV mutants from contemporary and historical strains	2019:2087	We generated nonglycosylated ZIKV mutants from contemporary and historical strains and evaluated their virulence in mice.
30944176	9	25	theme	cell-specific	1307:1319	arg1	DC-SIGN					1377:1383	DC-SIGN	1377:1383	DC-SIGN	1377:1383	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	25	theme	cell-specific	1307:1319	arg1	nonintegrin					1364:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin	1297:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)	1297:1384	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	7	26	theme	viral	974:978	arg1	loads					980:984	lower viral loads	968:984	lower viral loads	968:984	In contrast, nonglycosylated viruses were attenuated, producing lower viral loads in the serum and brain when inoculated subcutaneously but remaining neurovirulent when inoculated intracranially.
30944176	5	27	gly	glycosylation	674:686	arg1	ZIKV					691:694	ZIKV pathogenesis	691:707	ZIKV pathogenesis	691:707	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	9	28	theme	adhesion	1335:1342	arg1	DC-SIGN					1377:1383	DC-SIGN	1377:1383	DC-SIGN	1377:1383	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	28	theme	adhesion	1335:1342	arg1	nonintegrin					1364:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin	1297:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)	1297:1384	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	29	theme	virus	1604:1608	arg1	ability					1588:1594	the ability	1584:1594	the ability of Zika virus (ZIKV) to cause serious disease	1584:1640	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	30	dep	DC-SIGN-related	1389:1403	arg1	DC-SIGNR					1406:1413	DC-SIGNR	1406:1413	DC-SIGNR	1406:1413	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	5	31	theme	contemporary	719:730	arg1	H/PF/2013					755:763	H/PF/2013	755:763	H/PF/2013	755:763	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	31	theme	contemporary	719:730	arg1	strains					746:752	two contemporary Asian-lineage strains	715:752	two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59)	715:777	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	31	theme	contemporary	719:730	arg1	PRVABC59					769:776	PRVABC59	769:776	PRVABC59	769:776	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	4	32	theme	N-linked	494:501	arg1	site					517:520	an N-linked glycosylation site	491:520	an N-linked glycosylation site in the envelope (E) protein (N154)	491:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	32	theme	N-linked	494:501	arg1	isolates					475:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	33	gly	glycosylation	567:579	arg2	site					581:584	this glycosylation site	562:584	this glycosylation site	562:584	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	14	34	theme	leukocytes	2398:2407	arg1	infection					2367:2375	and infection	2363:2375	infection	2367:2375	Our studies suggest that envelope protein glycosylation contributes to ZIKV pathogenesis, possibly by facilitating attachment to and infection of lectin-expressing leukocytes.
30944176	0	35	theme	Envelope	0:7	arg1	Glycosylation					17:29	Envelope Protein Glycosylation	0:29	Envelope Protein Glycosylation	0:29	Envelope Protein Glycosylation Mediates Zika Virus Pathogenesis.
30944176	9	36	theme	serious	1626:1632	arg1	disease					1634:1640	serious disease	1626:1640	serious disease	1626:1640	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	3	37	theme	viral	382:386	arg1	changes					396:402	viral genetic changes	382:402	viral genetic changes	382:402	These outcomes were not associated with ZIKV infection prior to 2013, raising the possibility that viral genetic changes could contribute to new clinical manifestations.
30944176	10	38	theme	contributing	1743:1754	arg1	factor					1756:1761	One contributing factor	1739:1761	One contributing factor	1739:1761	One contributing factor could be genetic differences between contemporary ZIKV strains and historical ZIKV strains.
30944176	8	39	from	periphery	1166:1174	arg1	advantageous					1146:1157	advantageous	1146:1157	advantageous	1146:1157	These results suggest that E glycosylation is advantageous in the periphery but not within the brain.
30944176	1	40	theme	emerging	89:96	arg1	flavivirus					113:122	an emerging mosquito-borne flavivirus	86:122	an emerging mosquito-borne flavivirus	86:122	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus.
30944176	1	40	theme	emerging	89:96	arg1	virus					70:74	Zika virus	65:74	Zika virus (ZIKV)	65:81	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus.
30944176	3	41	theme	new	424:426	arg1	manifestations					437:450	new clinical manifestations	424:450	new clinical manifestations	424:450	These outcomes were not associated with ZIKV infection prior to 2013, raising the possibility that viral genetic changes could contribute to new clinical manifestations.
30944176	6	42	gly	glycosylated	844:855	arg1	viruses					857:863	glycosylated viruses	844:863	glycosylated viruses	844:863	We found that glycosylated viruses were highly pathogenic in Ifnar1 mice.
30944176	0	43	theme	Zika	40:43	arg1	Pathogenesis					51:62	Zika Virus Pathogenesis	40:62	Zika Virus Pathogenesis	40:62	Envelope Protein Glycosylation Mediates Zika Virus Pathogenesis.
30944176	6	44	theme	glycosylated	844:855	arg1	viruses					857:863	glycosylated viruses	844:863	glycosylated viruses	844:863	We found that glycosylated viruses were highly pathogenic in Ifnar1 mice.
30944176	9	45	theme	Guillain-Barré	1653:1666	arg1	syndrome					1668:1675	Guillain-Barré syndrome	1653:1675	Guillain-Barré syndrome	1653:1675	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	46	from	mice.IMPORTANCE	1550:1564	arg1	attenuation					1511:1521	the attenuation	1507:1521	the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks	1507:1736	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	14	47	gly	glycosylation	2276:2288	arg1	ZIKV					2305:2308	ZIKV pathogenesis	2305:2321	ZIKV pathogenesis	2305:2321	Our studies suggest that envelope protein glycosylation contributes to ZIKV pathogenesis, possibly by facilitating attachment to and infection of lectin-expressing leukocytes.
30944176	2	48	theme	serious	161:167	arg1	disease					175:181	serious human disease	161:181	serious human disease	161:181	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	10	49	theme	genetic	1772:1778	arg1	differences					1780:1790	genetic differences	1772:1790	genetic differences between contemporary ZIKV strains and historical ZIKV strains	1772:1852	One contributing factor could be genetic differences between contemporary ZIKV strains and historical ZIKV strains.
30944176	5	50	theme	historical	787:796	arg1	strain					814:819	the historical African-lineage strain	783:819	the historical African-lineage strain (MR766)	783:827	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	50	theme	historical	787:796	arg1	MR766					822:826	MR766	822:826	MR766	822:826	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	9	51	from	ZIKV	1542:1545	arg1	mice.IMPORTANCE					1550:1564	mice.IMPORTANCE	1550:1564	mice.IMPORTANCE	1550:1564	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	52	theme	inefficient	1433:1443	arg1	infection					1445:1453	inefficient infection	1433:1453	inefficient infection of lectin-expressing leukocytes	1433:1485	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	53	dep	ZIKV	1542:1545	arg1	unclear					1572:1578	unclear	1572:1578	unclear	1572:1578	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	10	54	theme	ZIKV	1813:1816	arg1	strains					1818:1824	contemporary ZIKV strains	1800:1824	contemporary ZIKV strains	1800:1824	One contributing factor could be genetic differences between contemporary ZIKV strains and historical ZIKV strains.
30944176	4	55	theme	historical	604:613	arg1	isolates					620:627	many historical ZIKV isolates	599:627	many historical ZIKV isolates	599:627	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	9	56	theme	leukocytes	1476:1485	arg1	infection					1445:1453	inefficient infection	1433:1453	inefficient infection of lectin-expressing leukocytes	1433:1485	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	4	57	theme	glycosylation	567:579	arg1	site					581:584	this glycosylation site	562:584	this glycosylation site	562:584	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	6	58	from	pathogenic	877:886	arg1	mice					898:901	Ifnar1 mice	891:901	Ifnar1 mice	891:901	We found that glycosylated viruses were highly pathogenic in Ifnar1 mice.
30944176	10	59	theme	ZIKV	1841:1844	arg1	strains					1846:1852	historical ZIKV strains	1830:1852	historical ZIKV strains	1830:1852	One contributing factor could be genetic differences between contemporary ZIKV strains and historical ZIKV strains.
30944176	6	60	theme	Ifnar1	891:896	arg1	mice					898:901	Ifnar1 mice	891:901	Ifnar1 mice	891:901	We found that glycosylated viruses were highly pathogenic in Ifnar1 mice.
30944176	9	61	theme	recent	1721:1726	arg1	outbreaks					1728:1736	recent outbreaks	1721:1736	recent outbreaks	1721:1736	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	2	62	theme	ZIKV	132:135	arg1	outbreaks					137:145	Recent ZIKV outbreaks	125:145	Recent ZIKV outbreaks	125:145	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	4	63	gly	glycosylation	503:515	arg2	isolates					475:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	63	gly	glycosylation	503:515	arg2	site					517:520	an N-linked glycosylation site	491:520	an N-linked glycosylation site in the envelope (E) protein (N154)	491:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	9	64	theme	ZIKV	1542:1545	arg1	attenuation					1511:1521	the attenuation	1507:1521	the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks	1507:1736	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	14	65	theme	envelope	2259:2266	arg1	glycosylation					2276:2288	envelope protein glycosylation	2259:2288	envelope protein glycosylation	2259:2288	Our studies suggest that envelope protein glycosylation contributes to ZIKV pathogenesis, possibly by facilitating attachment to and infection of lectin-expressing leukocytes.
30944176	11	66	theme	recent	1873:1878	arg1	outbreaks					1880:1888	recent outbreaks	1873:1888	recent outbreaks	1873:1888	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	4	67	from	isolates	620:627	arg1	absent					589:594	absent	589:594	absent	589:594	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	12	68	theme	ZIKV	2035:2038	arg1	mutants					2040:2046	nonglycosylated ZIKV mutants	2019:2046	nonglycosylated ZIKV mutants from contemporary and historical strains	2019:2087	We generated nonglycosylated ZIKV mutants from contemporary and historical strains and evaluated their virulence in mice.
30944176	9	69	gly	nonglycosylated	1526:1540	arg1	ZIKV					1542:1545	nonglycosylated ZIKV	1526:1545	nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks	1526:1736	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	70	theme	cells	1268:1272	arg1	infection					1255:1263	infection	1255:1263	infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR)	1255:1414	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	2	71	theme	Zika	239:242	arg1	syndrome					244:251	congenital Zika syndrome	228:251	congenital Zika syndrome	228:251	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	2	71	theme	Zika	239:242	arg1	malformations					213:225	neurodevelopmental malformations	194:225	neurodevelopmental malformations (congenital Zika syndrome)	194:252	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	1	72	theme	mosquito-borne	98:111	arg1	flavivirus					113:122	an emerging mosquito-borne flavivirus	86:122	an emerging mosquito-borne flavivirus	86:122	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus.
30944176	1	72	theme	mosquito-borne	98:111	arg1	virus					70:74	Zika virus	65:74	Zika virus (ZIKV)	65:81	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus.
30944176	13	73	theme	lower	2195:2199	arg1	loads					2207:2211	lower viral loads	2195:2211	lower viral loads	2195:2211	We found that nonglycosylated viruses were attenuated and produced lower viral loads in serum and brains.
30944176	5	74	dep	strains	746:752	arg1	H/PF/2013					755:763	H/PF/2013	755:763	H/PF/2013	755:763	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	74	dep	strains	746:752	arg1	strains					746:752	two contemporary Asian-lineage strains	715:752	two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59)	715:777	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	74	dep	strains	746:752	arg1	PRVABC59					769:776	PRVABC59	769:776	PRVABC59	769:776	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	11	75	theme	viral	1899:1903	arg1	isolates					1859:1866	All isolates	1855:1866	All isolates from recent outbreaks	1855:1888	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	11	75	theme	viral	1899:1903	arg1	protein					1914:1920	a viral envelope protein	1897:1920	a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation	1897:2003	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	5	76	theme	protein	666:672	arg1	glycosylation					674:686	E protein glycosylation	664:686	E protein glycosylation	664:686	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	4	77	theme	contemporary	457:468	arg1	site					517:520	an N-linked glycosylation site	491:520	an N-linked glycosylation site in the envelope (E) protein (N154)	491:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	77	theme	contemporary	457:468	arg1	isolates					475:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	9	78	theme	dendritic	1297:1305	arg1	DC-SIGN					1377:1383	DC-SIGN	1377:1383	DC-SIGN	1377:1383	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	78	theme	dendritic	1297:1305	arg1	nonintegrin					1364:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin	1297:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)	1297:1384	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	2	79	theme	Guillain-Barré	258:271	arg1	syndrome					273:280	Guillain-Barré syndrome	258:280	Guillain-Barré syndrome	258:280	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	4	80	theme	envelope	529:536	arg1	N154					551:554	N154	551:554	N154	551:554	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	80	theme	envelope	529:536	arg1	protein					542:548	the envelope (E) protein	525:548	the envelope (E) protein (N154)	525:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	9	81	theme	intercellular	1321:1333	arg1	DC-SIGN					1377:1383	DC-SIGN	1377:1383	DC-SIGN	1377:1383	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	81	theme	intercellular	1321:1333	arg1	nonintegrin					1364:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin	1297:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)	1297:1384	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	82	theme	Zika	1599:1602	arg1	ZIKV					1611:1614	ZIKV	1611:1614	ZIKV	1611:1614	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	82	theme	Zika	1599:1602	arg1	virus					1604:1608	Zika virus	1599:1608	Zika virus (ZIKV)	1599:1615	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	4	83	theme	E	539:539	arg1	N154					551:554	N154	551:554	N154	551:554	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	83	theme	E	539:539	arg1	protein					542:548	the envelope (E) protein	525:548	the envelope (E) protein (N154)	525:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	84	from	absent	589:594	arg1	isolates					620:627	many historical ZIKV isolates	599:627	many historical ZIKV isolates	599:627	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	9	85	theme	molecule-3-grabbing	1344:1362	arg1	DC-SIGN					1377:1383	DC-SIGN	1377:1383	DC-SIGN	1377:1383	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	9	85	theme	molecule-3-grabbing	1344:1362	arg1	nonintegrin					1364:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin	1297:1374	dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)	1297:1384	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	12	86	theme	nonglycosylated	2019:2033	arg1	mutants					2040:2046	nonglycosylated ZIKV mutants	2019:2046	nonglycosylated ZIKV mutants from contemporary and historical strains	2019:2087	We generated nonglycosylated ZIKV mutants from contemporary and historical strains and evaluated their virulence in mice.
30944176	7	87	theme	lower	968:972	arg1	loads					980:984	lower viral loads	968:984	lower viral loads	968:984	In contrast, nonglycosylated viruses were attenuated, producing lower viral loads in the serum and brain when inoculated subcutaneously but remaining neurovirulent when inoculated intracranially.
30944176	1	88	theme	Zika	65:68	arg1	ZIKV					77:80	ZIKV	77:80	ZIKV	77:80	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus.
30944176	1	88	theme	Zika	65:68	arg1	virus					70:74	Zika virus	65:74	Zika virus (ZIKV)	65:81	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus.
30944176	1	88	theme	Zika	65:68	arg1	flavivirus					113:122	an emerging mosquito-borne flavivirus	86:122	an emerging mosquito-borne flavivirus	86:122	Zika virus (ZIKV) is an emerging mosquito-borne flavivirus.
30944176	4	89	theme	glycosylation	503:515	arg1	site					517:520	an N-linked glycosylation site	491:520	an N-linked glycosylation site in the envelope (E) protein (N154)	491:555	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	4	89	theme	glycosylation	503:515	arg1	isolates					475:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates	453:482	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	7	90	dep	serum	993:997	arg1	the					989:991	the	989:991	the	989:991	In contrast, nonglycosylated viruses were attenuated, producing lower viral loads in the serum and brain when inoculated subcutaneously but remaining neurovirulent when inoculated intracranially.
30944176	5	91	theme	Asian-lineage	732:744	arg1	H/PF/2013					755:763	H/PF/2013	755:763	H/PF/2013	755:763	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	91	theme	Asian-lineage	732:744	arg1	strains					746:752	two contemporary Asian-lineage strains	715:752	two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59)	715:777	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	91	theme	Asian-lineage	732:744	arg1	PRVABC59					769:776	PRVABC59	769:776	PRVABC59	769:776	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	13	92	theme	nonglycosylated	2142:2156	arg1	viruses					2158:2164	nonglycosylated viruses	2142:2164	nonglycosylated viruses	2142:2164	We found that nonglycosylated viruses were attenuated and produced lower viral loads in serum and brains.
30944176	0	93	theme	Protein	9:15	arg1	Glycosylation					17:29	Envelope Protein Glycosylation	0:29	Envelope Protein Glycosylation	0:29	Envelope Protein Glycosylation Mediates Zika Virus Pathogenesis.
30944176	14	94	theme	lectin-expressing	2380:2396	arg1	leukocytes					2398:2407	lectin-expressing leukocytes	2380:2407	lectin-expressing leukocytes	2380:2407	Our studies suggest that envelope protein glycosylation contributes to ZIKV pathogenesis, possibly by facilitating attachment to and infection of lectin-expressing leukocytes.
30944176	7	95	theme	nonglycosylated	917:931	arg1	viruses					933:939	nonglycosylated viruses	917:939	nonglycosylated viruses	917:939	In contrast, nonglycosylated viruses were attenuated, producing lower viral loads in the serum and brain when inoculated subcutaneously but remaining neurovirulent when inoculated intracranially.
30944176	3	96	theme	genetic	388:394	arg1	changes					396:402	viral genetic changes	382:402	viral genetic changes	382:402	These outcomes were not associated with ZIKV infection prior to 2013, raising the possibility that viral genetic changes could contribute to new clinical manifestations.
30944176	11	97	theme	historical	1957:1966	arg1	strains					1973:1979	many historical ZIKV strains	1952:1979	many historical ZIKV strains	1952:1979	All isolates from recent outbreaks encode a viral envelope protein that is glycosylated, whereas many historical ZIKV strains lack this glycosylation.
30944176	0	98	theme	Virus	45:49	arg1	Pathogenesis					51:62	Zika Virus Pathogenesis	40:62	Zika Virus Pathogenesis	40:62	Envelope Protein Glycosylation Mediates Zika Virus Pathogenesis.
30944176	12	99	from	strains	2081:2087	arg1	mutants					2040:2046	nonglycosylated ZIKV mutants	2019:2046	nonglycosylated ZIKV mutants from contemporary and historical strains	2019:2087	We generated nonglycosylated ZIKV mutants from contemporary and historical strains and evaluated their virulence in mice.
30944176	3	100	theme	clinical	428:435	arg1	manifestations					437:450	new clinical manifestations	424:450	new clinical manifestations	424:450	These outcomes were not associated with ZIKV infection prior to 2013, raising the possibility that viral genetic changes could contribute to new clinical manifestations.
30944176	2	101	theme	human	169:173	arg1	disease					175:181	serious human disease	161:181	serious human disease	161:181	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	4	102	theme	ZIKV	615:618	arg1	isolates					620:627	many historical ZIKV isolates	599:627	many historical ZIKV isolates	599:627	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	5	103	from	role	656:659	arg1	pathogenesis					696:707	ZIKV pathogenesis	691:707	ZIKV pathogenesis	691:707	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	8	104	theme	E	1127:1127	arg1	glycosylation					1129:1141	E glycosylation	1127:1141	E glycosylation	1127:1141	These results suggest that E glycosylation is advantageous in the periphery but not within the brain.
30944176	8	105	from	advantageous	1146:1157	arg1	periphery					1166:1174	the periphery	1162:1174	the periphery	1162:1174	These results suggest that E glycosylation is advantageous in the periphery but not within the brain.
30944176	9	106	theme	birth	1681:1685	arg1	defects					1687:1693	birth defects	1681:1693	birth defects	1681:1693	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30944176	4	107	theme	many	599:602	arg1	isolates					620:627	many historical ZIKV isolates	599:627	many historical ZIKV isolates	599:627	All contemporary ZIKV isolates encode an N-linked glycosylation site in the envelope (E) protein (N154), but this glycosylation site is absent in many historical ZIKV isolates.
30944176	2	108	theme	neurodevelopmental	194:211	arg1	syndrome					244:251	congenital Zika syndrome	228:251	congenital Zika syndrome	228:251	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	2	108	theme	neurodevelopmental	194:211	arg1	malformations					213:225	neurodevelopmental malformations	194:225	neurodevelopmental malformations (congenital Zika syndrome)	194:252	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	10	109	theme	contemporary	1800:1811	arg1	strains					1818:1824	contemporary ZIKV strains	1800:1824	contemporary ZIKV strains	1800:1824	One contributing factor could be genetic differences between contemporary ZIKV strains and historical ZIKV strains.
30944176	7	110	gly	nonglycosylated	917:931	arg1	viruses					933:939	nonglycosylated viruses	917:939	nonglycosylated viruses	917:939	In contrast, nonglycosylated viruses were attenuated, producing lower viral loads in the serum and brain when inoculated subcutaneously but remaining neurovirulent when inoculated intracranially.
30944176	6	111	from	mice	898:901	arg1	pathogenic					877:886	pathogenic	877:886	pathogenic	877:886	We found that glycosylated viruses were highly pathogenic in Ifnar1 mice.
30944176	2	112	theme	Recent	125:130	arg1	outbreaks					137:145	Recent ZIKV outbreaks	125:145	Recent ZIKV outbreaks	125:145	Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome.
30944176	5	113	theme	African-lineage	798:812	arg1	strain					814:819	the historical African-lineage strain	783:819	the historical African-lineage strain (MR766)	783:827	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	5	113	theme	African-lineage	798:812	arg1	MR766					822:826	MR766	822:826	MR766	822:826	Here, we investigated the role of E protein glycosylation in ZIKV pathogenesis using two contemporary Asian-lineage strains (H/PF/2013 and PRVABC59) and the historical African-lineage strain (MR766).
30944176	9	114	theme	lectin-expressing	1458:1474	arg1	leukocytes					1476:1485	lectin-expressing leukocytes	1458:1485	lectin-expressing leukocytes	1458:1485	Accordingly, we found that glycosylation facilitated infection of cells expressing the lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) or DC-SIGN-related (DC-SIGNR), suggesting that inefficient infection of lectin-expressing leukocytes could contribute to the attenuation of nonglycosylated ZIKV in mice.IMPORTANCE It is unclear why the ability of Zika virus (ZIKV) to cause serious disease, including Guillain-Barré syndrome and birth defects, was not recognized until recent outbreaks.
30486487	8	0	theme	Th2-type	1092:1099	arg1	response					1108:1115	a Th2-type immune response	1090:1115	a Th2-type immune response	1090:1115	This observation indicates that the E2 subunit vaccine induces a Th2-type immune response.
30486487	5	1	theme	E2	573:574	arg1	protein					576:582	E2 protein	573:582	E2 protein	573:582	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	7	2	theme	interleukin-10	936:949	arg1	secretion					951:959	higher interleukin-10 secretion	929:959	higher interleukin-10 secretion	929:959	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	4	3	theme	E2	497:498	arg1	protein					500:506	E2 protein	497:506	E2 protein	497:506	In this study, E2 protein was successfully expressed by the baculovirus expression system.
30486487	0	4	theme	Pestivirus	58:67	arg1	Protein					30:36	E2 Protein	27:36	E2 Protein of Atypical Porcine Pestivirus	27:67	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice.
30486487	9	5	theme	infection	1234:1242	arg1	control					1218:1224	the control	1214:1224	the control of APPV infection	1214:1242	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	0	6	theme	Immune	86:91	arg1	Response					93:100	Th2-type Immune Response	77:100	Th2-type Immune Response	77:100	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice.
30486487	6	7	theme	E2	712:713	arg1	vaccine					723:729	E2 subunit vaccine	712:729	E2 subunit vaccine	712:729	The immunogenicity of E2 subunit vaccine was evaluated in mice.
30486487	9	8	theme	E2	1142:1143	arg1	protein					1145:1151	E2 protein	1142:1151	E2 protein	1142:1151	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	9	8	theme	E2	1142:1143	arg1	vaccine					1202:1208	a safe and effective subunit vaccine	1173:1208	a safe and effective subunit vaccine for the control of APPV infection	1173:1242	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	2	9	theme	cases	252:256	arg1	number					242:247	An increased number	229:247	An increased number of cases of APPV	229:264	An increased number of cases of APPV have been reported in various countries all over the world since 2015.
30486487	0	10	theme	Th2-type	77:84	arg1	Response					93:100	Th2-type Immune Response	77:100	Th2-type Immune Response	77:100	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice.
30486487	5	11	gly	glycosylation	669:681	arg2	sites					683:687	N-linked glycosylation sites	660:687	N-linked glycosylation sites	660:687	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	7	12	theme	lymphocyte	890:899	arg1	responses					915:923	stronger lymphocyte proliferative responses	881:923	stronger lymphocyte proliferative responses	881:923	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	3	13	theme	APPV	476:479	arg1	protein					423:429	the E2 protein	416:429	the E2 protein	416:429	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	3	13	theme	APPV	476:479	arg1	protein					465:471	the main immunogenicity protein	441:471	the main immunogenicity protein of APPV	441:479	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	3	14	theme	E2	420:421	arg1	protein					423:429	the E2 protein	416:429	the E2 protein	416:429	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	3	14	theme	E2	420:421	arg1	protein					465:471	the main immunogenicity protein	441:471	the main immunogenicity protein of APPV	441:479	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	5	15	contain	possesses	650:658	arg2	sites					683:687	N-linked glycosylation sites	660:687	N-linked glycosylation sites	660:687	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	5	15	contain	possesses	650:658	arg1	protein					642:648	E2 protein	639:648	E2 protein	639:648	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	6	16	theme	vaccine	723:729	arg1	immunogenicity					694:707	The immunogenicity	690:707	The immunogenicity of E2 subunit vaccine	690:729	The immunogenicity of E2 subunit vaccine was evaluated in mice.
30486487	3	17	theme	immunogenicity	450:463	arg1	protein					423:429	the E2 protein	416:429	the E2 protein	416:429	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	3	17	theme	immunogenicity	450:463	arg1	protein					465:471	the main immunogenicity protein	441:471	the main immunogenicity protein of APPV	441:479	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	3	18	theme	subunit	378:384	arg1	vaccine					386:392	an effective subunit vaccine	365:392	an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV	365:479	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	5	19	theme	N-linked	660:667	arg1	sites					683:687	N-linked glycosylation sites	660:687	N-linked glycosylation sites	660:687	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	6	20	theme	subunit	715:721	arg1	vaccine					723:729	E2 subunit vaccine	712:729	E2 subunit vaccine	712:729	The immunogenicity of E2 subunit vaccine was evaluated in mice.
30486487	2	21	theme	increased	232:240	arg1	number					242:247	An increased number	229:247	An increased number of cases of APPV	229:264	An increased number of cases of APPV have been reported in various countries all over the world since 2015.
30486487	0	22	theme	Subunit	2:8	arg1	Vaccine					10:16	A Subunit Vaccine	0:16	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus	0:67	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice.
30486487	8	23	theme	immune	1101:1106	arg1	response					1108:1115	a Th2-type immune response	1090:1115	a Th2-type immune response	1090:1115	This observation indicates that the E2 subunit vaccine induces a Th2-type immune response.
30486487	5	24	theme	glycosylation	669:681	arg1	sites					683:687	N-linked glycosylation sites	660:687	N-linked glycosylation sites	660:687	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	8	25	theme	E2	1063:1064	arg1	vaccine					1074:1080	the E2 subunit vaccine	1059:1080	the E2 subunit vaccine	1059:1080	This observation indicates that the E2 subunit vaccine induces a Th2-type immune response.
30486487	1	26	theme	congenital	157:166	arg1	A-II					180:183	congenital tremor type A-II	157:183	congenital tremor type A-II	157:183	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016.
30486487	7	27	theme	antibodies	857:866	arg1	levels					833:838	significantly higher levels	812:838	significantly higher levels of APPV-specific antibodies	812:866	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	3	28	theme	effective	368:376	arg1	vaccine					386:392	an effective subunit vaccine	365:392	an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV	365:479	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	7	29	theme	proliferative	901:913	arg1	responses					915:923	stronger lymphocyte proliferative responses	881:923	stronger lymphocyte proliferative responses	881:923	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	2	30	dep	countries	296:304	arg1	all					306:308	all	306:308	all	306:308	An increased number of cases of APPV have been reported in various countries all over the world since 2015.
30486487	7	31	theme	E2	758:759	arg1	protein					761:767	The E2 protein	754:767	The E2 protein emulsified with ISA 201VG adjuvant	754:802	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	1	32	theme	type	175:178	arg1	A-II					180:183	congenital tremor type A-II	157:183	congenital tremor type A-II	157:183	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016.
30486487	9	33	theme	safe	1175:1178	arg1	protein					1145:1151	E2 protein	1142:1151	E2 protein	1142:1151	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	9	33	theme	safe	1175:1178	arg1	vaccine					1202:1208	a safe and effective subunit vaccine	1173:1208	a safe and effective subunit vaccine for the control of APPV infection	1173:1242	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	4	34	theme	baculovirus	542:552	arg1	system					565:570	the baculovirus expression system	538:570	the baculovirus expression system	538:570	In this study, E2 protein was successfully expressed by the baculovirus expression system.
30486487	0	35	theme	E2	27:28	arg1	Protein					30:36	E2 Protein	27:36	E2 Protein of Atypical Porcine Pestivirus	27:67	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice.
30486487	1	36	theme	tremor	168:173	arg1	A-II					180:183	congenital tremor type A-II	157:183	congenital tremor type A-II	157:183	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016.
30486487	7	37	theme	adjuvant	1017:1024	arg1	IMS					1006:1008	IMS	1006:1008	IMS 1313VG adjuvant	1006:1024	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	9	38	theme	effective	1184:1192	arg1	protein					1145:1151	E2 protein	1142:1151	E2 protein	1142:1151	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	9	38	theme	effective	1184:1192	arg1	vaccine					1202:1208	a safe and effective subunit vaccine	1173:1208	a safe and effective subunit vaccine for the control of APPV infection	1173:1242	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	5	39	theme	E2	639:640	arg1	protein					642:648	E2 protein	639:648	E2 protein	639:648	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	8	40	theme	subunit	1066:1072	arg1	vaccine					1074:1080	the E2 subunit vaccine	1059:1080	the E2 subunit vaccine	1059:1080	This observation indicates that the E2 subunit vaccine induces a Th2-type immune response.
30486487	9	41	theme	subunit	1194:1200	arg1	protein					1145:1151	E2 protein	1142:1151	E2 protein	1142:1151	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	9	41	theme	subunit	1194:1200	arg1	vaccine					1202:1208	a safe and effective subunit vaccine	1173:1208	a safe and effective subunit vaccine for the control of APPV infection	1173:1242	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	7	42	theme	E2	979:980	arg1	protein					982:988	the E2 protein	975:988	the E2 protein emulsified with IMS 1313VG adjuvant	975:1024	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	7	43	theme	stronger	881:888	arg1	responses					915:923	stronger lymphocyte proliferative responses	881:923	stronger lymphocyte proliferative responses	881:923	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	5	44	theme	Western	601:607	arg1	assay					614:618	Western blot assay	601:618	Western blot assay	601:618	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	9	45	theme	APPV	1229:1232	arg1	infection					1234:1242	APPV infection	1229:1242	APPV infection	1229:1242	Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
30486487	2	46	theme	various	288:294	arg1	countries					296:304	various countries	288:304	various countries all over the world since 2015	288:334	An increased number of cases of APPV have been reported in various countries all over the world since 2015.
30486487	5	47	theme	blot	609:612	arg1	assay					614:618	Western blot assay	601:618	Western blot assay	601:618	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	2	48	theme	APPV	261:264	arg1	cases					252:256	cases	252:256	cases of APPV	252:264	An increased number of cases of APPV have been reported in various countries all over the world since 2015.
30486487	1	49	theme	atypical	114:121	arg1	pestivirus					131:140	An atypical porcine pestivirus	111:140	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets	111:194	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016.
30486487	1	49	theme	atypical	114:121	arg1	APPV					143:146	APPV	143:146	APPV	143:146	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016.
30486487	7	50	theme	higher	826:831	arg1	levels					833:838	significantly higher levels	812:838	significantly higher levels of APPV-specific antibodies	812:866	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	0	51	theme	Porcine	50:56	arg1	Pestivirus					58:67	Atypical Porcine Pestivirus	41:67	Atypical Porcine Pestivirus	41:67	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice.
30486487	5	52	link	N-linked	660:667	arg1	sites					683:687	N-linked glycosylation sites	660:687	N-linked glycosylation sites	660:687	E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites.
30486487	4	53	theme	expression	554:563	arg1	system					565:570	the baculovirus expression system	538:570	the baculovirus expression system	538:570	In this study, E2 protein was successfully expressed by the baculovirus expression system.
30486487	1	54	theme	porcine	123:129	arg1	pestivirus					131:140	An atypical porcine pestivirus	111:140	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets	111:194	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016.
30486487	1	54	theme	porcine	123:129	arg1	APPV					143:146	APPV	143:146	APPV	143:146	An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016.
30486487	7	55	theme	APPV-specific	843:855	arg1	antibodies					857:866	APPV-specific antibodies	843:866	APPV-specific antibodies	843:866	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	0	56	theme	Atypical	41:48	arg1	Pestivirus					58:67	Atypical Porcine Pestivirus	41:67	Atypical Porcine Pestivirus	41:67	A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice.
30486487	7	57	theme	higher	929:934	arg1	secretion					951:959	higher interleukin-10 secretion	929:959	higher interleukin-10 secretion	929:959	The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant.
30486487	3	58	theme	main	445:448	arg1	protein					423:429	the E2 protein	416:429	the E2 protein	416:429	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30486487	3	58	theme	main	445:448	arg1	protein					465:471	the main immunogenicity protein	441:471	the main immunogenicity protein of APPV	441:479	This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV.
30481169	4	0	theme	N-linked	840:847	arg1	glycosylation					857:869	N-linked protein glycosylation	840:869	N-linked protein glycosylation	840:869	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	7	1	theme	Gb3	1238:1240	arg1	synthesis					1242:1250	Gb3 synthesis	1238:1250	Gb3 synthesis	1238:1250	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	2	theme	LAPTM4A	1426:1432	arg1	LAPTM4A					1426:1432	LAPTM4A	1426:1432	LAPTM4A	1426:1432	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	2	theme	LAPTM4A	1426:1432	arg1	domain					1416:1421	the second luminal domain	1397:1421	the second luminal domain of LAPTM4A	1397:1432	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	11	3	theme	glycolipid	2080:2089	arg1	synthesis					2091:2099	glycolipid synthesis	2080:2099	glycolipid synthesis	2080:2099	These studies reveal key Golgi proteins critical for regulating glycosylation and glycolipid synthesis and provide novel therapeutic targets for blocking Stxs and ricin toxicity.
30481169	2	4	dep	tools	252:256	arg1	identify					261:268	identify	261:268	to identify key players in glycosylation processes	258:307	Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes.
30481169	2	5	theme	key	270:272	arg1	players					274:280	key players	270:280	key players in glycosylation processes	270:307	Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes.
30481169	7	6	theme	second	1401:1406	arg1	LAPTM4A					1426:1432	LAPTM4A	1426:1432	LAPTM4A	1426:1432	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	6	theme	second	1401:1406	arg1	domain					1416:1421	the second luminal domain	1397:1421	the second luminal domain of LAPTM4A	1397:1432	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	9	7	theme	proper	1868:1873	arg1	levels					1875:1880	proper levels	1868:1880	proper levels of glycosylation in general	1868:1908	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	9	8	from	levels	1875:1880	arg1	general					1902:1908	general	1902:1908	general	1902:1908	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	11	9	theme	key	2019:2021	arg1	proteins					2029:2036	key Golgi proteins	2019:2036	key Golgi proteins critical for regulating glycosylation and glycolipid synthesis	2019:2099	These studies reveal key Golgi proteins critical for regulating glycosylation and glycolipid synthesis and provide novel therapeutic targets for blocking Stxs and ricin toxicity.
30481169	2	10	from	players	274:280	arg1	processes					299:307	glycosylation processes	285:307	glycosylation processes	285:307	Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes.
30481169	4	11	theme	major	693:697	arg1	GTs					721:723	GTs	721:723	GTs	721:723	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	4	11	theme	major	693:697	arg1	glycosyltransferases					699:718	major glycosyltransferases	693:718	major glycosyltransferases (GTs)	693:724	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	10	12	theme	KO	1944:1945	arg1	cells					1947:1951	TM9SF2 KO cells	1937:1951	TM9SF2 KO cells	1937:1951	In addition, TM9SF2 KO cells also showed defective endosomal trafficking.
30481169	3	13	theme	plant	603:607	arg1	ricin					615:619	the plant toxin ricin	599:619	the plant toxin ricin	599:619	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	5	14	theme	lysosomal-associated	917:936	arg1	protein					1021:1027	a poorly characterized four-pass membrane protein	979:1027	a poorly characterized four-pass membrane protein	979:1027	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	14	theme	lysosomal-associated	917:936	arg1	alpha					962:966	lysosomal-associated protein transmembrane 4 alpha	917:966	lysosomal-associated protein transmembrane 4 alpha (LAPTM4A)	917:976	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	14	theme	lysosomal-associated	917:936	arg1	factor					1035:1040	a factor	1033:1040	a factor specifically required for Stxs	1033:1071	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	14	theme	lysosomal-associated	917:936	arg1	LAPTM4A					969:975	LAPTM4A	969:975	LAPTM4A	969:975	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	11	15	theme	critical	2038:2045	arg1	proteins					2029:2036	key Golgi proteins	2019:2036	key Golgi proteins critical for regulating glycosylation and glycolipid synthesis	2019:2099	These studies reveal key Golgi proteins critical for regulating glycosylation and glycolipid synthesis and provide novel therapeutic targets for blocking Stxs and ricin toxicity.
30481169	7	16	theme	transmembrane	1310:1322	arg1	LAPTM4B					1332:1338	LAPTM4B	1332:1338	LAPTM4B	1332:1338	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	16	theme	transmembrane	1310:1322	arg1	beta					1326:1329	its homolog lysosomal-associated protein transmembrane 4 beta	1269:1329	its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B)	1269:1339	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	9	17	gly	glycosylation	1885:1897	arg1	general					1902:1908	general	1902:1908	general	1902:1908	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	3	18	theme	specific	531:538	arg1	globotriaosylceramide					552:572	globotriaosylceramide	552:572	globotriaosylceramide (Gb3)	552:578	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	18	theme	specific	531:538	arg1	glycolipid					540:549	a specific glycolipid	529:549	a specific glycolipid	529:549	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	2	19	theme	powerful	243:250	arg1	tools					252:256	powerful tools	243:256	powerful tools to identify key players in glycosylation processes	243:307	Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes.
30481169	1	20	theme	proteins	151:158	arg1	modification					135:146	a fundamental modification	121:146	a fundamental modification of proteins and membrane lipids	121:178	Glycosylation is a fundamental modification of proteins and membrane lipids.
30481169	1	20	theme	proteins	151:158	arg1	Glycosylation					104:116	Glycosylation	104:116	Glycosylation	104:116	Glycosylation is a fundamental modification of proteins and membrane lipids.
30481169	10	21	theme	defective	1965:1973	arg1	trafficking					1985:1995	defective endosomal trafficking	1965:1995	defective endosomal trafficking	1965:1995	In addition, TM9SF2 KO cells also showed defective endosomal trafficking.
30481169	1	22	theme	membrane	164:171	arg1	lipids					173:178	membrane lipids	164:178	membrane lipids	164:178	Glycosylation is a fundamental modification of proteins and membrane lipids.
30481169	3	23	theme	Short	363:367	arg1	CRISPR					390:395	CRISPR	390:395	CRISPR	390:395	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	23	theme	Short	363:367	arg1	Repeats					381:387	Clustered Regularly Interspaced Short Palindromic Repeats	331:387	Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	331:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	9	24	theme	TM9SF2	1727:1732	arg1	cells					1737:1741	TMEM165 KO and TM9SF2 KO cells	1712:1741	cells	1737:1741	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	3	25	dep	-Cas9-mediated	397:410	arg1	screens					441:447	genome-wide loss-of-function screens	412:447	genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	412:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	26	theme	related	459:465	arg1	toxins					477:482	two related bacterial toxins	455:482	two related bacterial toxins	455:482	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	26	theme	related	459:465	arg1	toxins					496:501	Shiga-like toxins	485:501	Shiga-like toxins (Stxs) 1 and 2	485:516	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	11	27	theme	novel	2113:2117	arg1	targets					2131:2137	novel therapeutic targets	2113:2137	novel therapeutic targets for blocking Stxs and ricin toxicity	2113:2174	These studies reveal key Golgi proteins critical for regulating glycosylation and glycolipid synthesis and provide novel therapeutic targets for blocking Stxs and ricin toxicity.
30481169	0	28	theme	Golgi	61:65	arg1	proteins					67:74	Golgi proteins	61:74	Golgi proteins critical for glycosylation	61:101	Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation.
30481169	0	29	theme	Genome-wide	0:10	arg1	screens					19:25	Genome-wide CRISPR screens	0:25	Genome-wide CRISPR screens for Shiga toxins and ricin	0:52	Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation.
30481169	5	30	theme	transmembrane	946:958	arg1	protein					1021:1027	a poorly characterized four-pass membrane protein	979:1027	a poorly characterized four-pass membrane protein	979:1027	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	30	theme	transmembrane	946:958	arg1	alpha					962:966	lysosomal-associated protein transmembrane 4 alpha	917:966	lysosomal-associated protein transmembrane 4 alpha (LAPTM4A)	917:976	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	30	theme	transmembrane	946:958	arg1	factor					1035:1040	a factor	1033:1040	a factor specifically required for Stxs	1033:1071	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	30	theme	transmembrane	946:958	arg1	LAPTM4A					969:975	LAPTM4A	969:975	LAPTM4A	969:975	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	3	31	theme	Shiga-like	485:494	arg1	Stxs					504:507	Stxs	504:507	Stxs	504:507	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	31	theme	Shiga-like	485:494	arg1	toxins					477:482	two related bacterial toxins	455:482	two related bacterial toxins	455:482	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	31	theme	Shiga-like	485:494	arg1	toxins					496:501	Shiga-like toxins	485:501	Shiga-like toxins (Stxs) 1 and 2	485:516	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	32	theme	loss-of-function	424:439	arg1	screens					441:447	genome-wide loss-of-function screens	412:447	genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	412:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	7	33	theme	lysosomal-associated	1281:1300	arg1	LAPTM4B					1332:1338	LAPTM4B	1332:1338	LAPTM4B	1332:1338	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	33	theme	lysosomal-associated	1281:1300	arg1	beta					1326:1329	its homolog lysosomal-associated protein transmembrane 4 beta	1269:1329	its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B)	1269:1339	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	4	34	theme	ricin	783:787	arg1	screen					789:794	the ricin screen	779:794	the ricin screen	779:794	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	0	35	theme	Shiga	31:35	arg1	toxins					37:42	Shiga toxins	31:42	Shiga toxins	31:42	Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation.
30481169	7	36	theme	protein	1302:1308	arg1	LAPTM4B					1332:1338	LAPTM4B	1332:1338	LAPTM4B	1332:1338	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	36	theme	protein	1302:1308	arg1	beta					1326:1329	its homolog lysosomal-associated protein transmembrane 4 beta	1269:1329	its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B)	1269:1339	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	3	37	theme	-Cas9-mediated	397:410	arg1	CRISPR					390:395	CRISPR	390:395	CRISPR	390:395	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	37	theme	-Cas9-mediated	397:410	arg1	Repeats					381:387	Clustered Regularly Interspaced Short Palindromic Repeats	331:387	Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	331:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	6	38	theme	precursors	1126:1135	arg1	analysis					1092:1099	Mass spectrometry analysis	1074:1099	Mass spectrometry analysis of glycolipids and their precursors	1074:1135	Mass spectrometry analysis of glycolipids and their precursors demonstrates that LAPTM4A knockout (KO) cells lack Gb3 biosynthesis.
30481169	8	39	theme	Golgi	1557:1561	arg1	protein					1587:1593	Transmembrane protein 165	1573:1597	Transmembrane protein 165 (TMEM165)	1573:1607	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	39	theme	Golgi	1557:1561	arg1	factors					1670:1676	shared factors	1663:1676	shared factors required for both Stxs and ricin	1663:1709	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	39	theme	Golgi	1557:1561	arg1	TM9SF2					1651:1656	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	39	theme	Golgi	1557:1561	arg1	proteins					1563:1570	two Golgi proteins	1553:1570	two Golgi proteins	1553:1570	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	40	theme	Transmembrane	1613:1625	arg1	TM9SF2					1651:1656	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	40	theme	Transmembrane	1613:1625	arg1	proteins					1563:1570	two Golgi proteins	1553:1570	two Golgi proteins	1553:1570	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	7	41	theme	activator	1481:1489	arg1	"					1490:1490	a specific "activator"	1469:1490	a specific "activator" for the GT that synthesizes Gb3	1469:1522	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	3	42	contain	carried	319:325	arg2	Repeats					381:387	Clustered Regularly Interspaced Short Palindromic Repeats	331:387	Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	331:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	42	contain	carried	319:325	arg1	we					316:317	we	316:317	we	316:317	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	42	contain	carried	319:325	arg2	ricin					615:619	the plant toxin ricin	599:619	the plant toxin ricin	599:619	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	42	contain	carried	319:325	arg2	CRISPR					390:395	CRISPR	390:395	CRISPR	390:395	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	8	43	theme	superfamily	1629:1639	arg1	TM9SF2					1651:1656	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	43	theme	superfamily	1629:1639	arg1	proteins					1563:1570	two Golgi proteins	1553:1570	two Golgi proteins	1553:1570	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	7	44	theme	specific	1471:1478	arg1	"					1490:1490	a specific "activator"	1469:1490	a specific "activator" for the GT that synthesizes Gb3	1469:1522	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	5	45	theme	four-pass	1002:1010	arg1	protein					1021:1027	a poorly characterized four-pass membrane protein	979:1027	a poorly characterized four-pass membrane protein	979:1027	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	45	theme	four-pass	1002:1010	arg1	alpha					962:966	lysosomal-associated protein transmembrane 4 alpha	917:966	lysosomal-associated protein transmembrane 4 alpha (LAPTM4A)	917:976	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	9	46	from	reduction	1757:1765	arg1	Gb3					1779:1781	Gb3	1779:1781	not only Gb3 but also other glycosphingolipids	1770:1815	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	9	46	from	reduction	1757:1765	arg1	glycosphingolipids					1798:1815	other glycosphingolipids	1792:1815	not only Gb3 but also other glycosphingolipids	1770:1815	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	6	47	theme	spectrometry	1079:1090	arg1	analysis					1092:1099	Mass spectrometry analysis	1074:1099	Mass spectrometry analysis of glycolipids and their precursors	1074:1135	Mass spectrometry analysis of glycolipids and their precursors demonstrates that LAPTM4A knockout (KO) cells lack Gb3 biosynthesis.
30481169	3	48	theme	glycans	656:662	arg1	range					647:651	a broad range	639:651	a broad range of glycans	639:662	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	2	49	theme	glycosylation	285:297	arg1	processes					299:307	glycosylation processes	285:307	glycosylation processes	285:307	Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes.
30481169	4	50	theme	protein	849:855	arg1	glycosylation					857:869	N-linked protein glycosylation	840:869	N-linked protein glycosylation	840:869	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	1	51	theme	lipids	173:178	arg1	modification					135:146	a fundamental modification	121:146	a fundamental modification of proteins and membrane lipids	121:178	Glycosylation is a fundamental modification of proteins and membrane lipids.
30481169	1	51	theme	lipids	173:178	arg1	Glycosylation					104:116	Glycosylation	104:116	Glycosylation	104:116	Glycosylation is a fundamental modification of proteins and membrane lipids.
30481169	9	52	theme	TMEM165	1712:1718	arg1	KO					1720:1721	TMEM165 KO and TM9SF2 KO cells	1712:1741	KO	1720:1721	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	8	53	theme	shared	1663:1668	arg1	factors					1670:1676	shared factors	1663:1676	shared factors required for both Stxs and ricin	1663:1709	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	53	theme	shared	1663:1668	arg1	proteins					1563:1570	two Golgi proteins	1553:1570	two Golgi proteins	1553:1570	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	7	54	theme	luminal	1408:1414	arg1	LAPTM4A					1426:1432	LAPTM4A	1426:1432	LAPTM4A	1426:1432	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	54	theme	luminal	1408:1414	arg1	domain					1416:1421	the second luminal domain	1397:1421	the second luminal domain of LAPTM4A	1397:1432	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	6	55	dep	knockout	1163:1170	arg1	KO					1173:1174	KO	1173:1174	KO	1173:1174	Mass spectrometry analysis of glycolipids and their precursors demonstrates that LAPTM4A knockout (KO) cells lack Gb3 biosynthesis.
30481169	4	56	link	N-linked	840:847	arg1	glycosylation					857:869	N-linked protein glycosylation	840:869	N-linked protein glycosylation	840:869	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	6	57	theme	knockout	1163:1170	arg1	cells					1177:1181	LAPTM4A knockout (KO) cells	1155:1181	LAPTM4A knockout (KO) cells	1155:1181	Mass spectrometry analysis of glycolipids and their precursors demonstrates that LAPTM4A knockout (KO) cells lack Gb3 biosynthesis.
30481169	7	58	theme	homolog	1273:1279	arg1	LAPTM4B					1332:1338	LAPTM4B	1332:1338	LAPTM4B	1332:1338	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	7	58	theme	homolog	1273:1279	arg1	beta					1326:1329	its homolog lysosomal-associated protein transmembrane 4 beta	1269:1329	its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B)	1269:1339	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	9	59	theme	glycosylation	1885:1897	arg1	levels					1875:1880	proper levels	1868:1880	proper levels of glycosylation in general	1868:1908	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	11	60	theme	Golgi	2023:2027	arg1	proteins					2029:2036	key Golgi proteins	2019:2036	key Golgi proteins critical for regulating glycosylation and glycolipid synthesis	2019:2099	These studies reveal key Golgi proteins critical for regulating glycosylation and glycolipid synthesis and provide novel therapeutic targets for blocking Stxs and ricin toxicity.
30481169	4	61	theme	Stxs	669:672	arg1	screens					674:680	The Stxs screens	665:680	The Stxs screens	665:680	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	1	62	theme	fundamental	123:133	arg1	modification					135:146	a fundamental modification	121:146	a fundamental modification of proteins and membrane lipids	121:178	Glycosylation is a fundamental modification of proteins and membrane lipids.
30481169	1	62	theme	fundamental	123:133	arg1	Glycosylation					104:116	Glycosylation	104:116	Glycosylation	104:116	Glycosylation is a fundamental modification of proteins and membrane lipids.
30481169	10	63	theme	TM9SF2	1937:1942	arg1	cells					1947:1951	TM9SF2 KO cells	1937:1951	TM9SF2 KO cells	1937:1951	In addition, TM9SF2 KO cells also showed defective endosomal trafficking.
30481169	7	64	theme	LAPTM4A	1226:1232	arg1	requirement					1211:1221	This requirement	1206:1221	This requirement of LAPTM4A for Gb3 synthesis	1206:1250	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	3	65	theme	Clustered	331:339	arg1	CRISPR					390:395	CRISPR	390:395	CRISPR	390:395	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	65	theme	Clustered	331:339	arg1	Repeats					381:387	Clustered Regularly Interspaced Short Palindromic Repeats	331:387	Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	331:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	6	66	theme	Gb3	1188:1190	arg1	biosynthesis					1192:1203	Gb3 biosynthesis	1188:1203	Gb3 biosynthesis	1188:1203	Mass spectrometry analysis of glycolipids and their precursors demonstrates that LAPTM4A knockout (KO) cells lack Gb3 biosynthesis.
30481169	0	67	theme	critical	76:83	arg1	proteins					67:74	Golgi proteins	61:74	Golgi proteins critical for glycosylation	61:101	Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation.
30481169	11	68	theme	ricin	2161:2165	arg1	toxicity					2167:2174	ricin toxicity	2161:2174	ricin toxicity	2161:2174	These studies reveal key Golgi proteins critical for regulating glycosylation and glycolipid synthesis and provide novel therapeutic targets for blocking Stxs and ricin toxicity.
30481169	7	69	dep	shared	1259:1264	arg1	determined					1381:1390	determined	1381:1390	determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3	1381:1522	This requirement of LAPTM4A for Gb3 synthesis is not shared by its homolog lysosomal-associated protein transmembrane 4 beta (LAPTM4B), and switching the domains between them determined that the second luminal domain of LAPTM4A is required, potentially acting as a specific "activator" for the GT that synthesizes Gb3.
30481169	3	70	theme	Palindromic	369:379	arg1	CRISPR					390:395	CRISPR	390:395	CRISPR	390:395	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	70	theme	Palindromic	369:379	arg1	Repeats					381:387	Clustered Regularly Interspaced Short Palindromic Repeats	331:387	Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	331:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	6	71	theme	Mass	1074:1077	arg1	analysis					1092:1099	Mass spectrometry analysis	1074:1099	Mass spectrometry analysis of glycolipids and their precursors	1074:1135	Mass spectrometry analysis of glycolipids and their precursors demonstrates that LAPTM4A knockout (KO) cells lack Gb3 biosynthesis.
30481169	3	72	theme	Interspaced	351:361	arg1	CRISPR					390:395	CRISPR	390:395	CRISPR	390:395	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	72	theme	Interspaced	351:361	arg1	Repeats					381:387	Clustered Regularly Interspaced Short Palindromic Repeats	331:387	Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	331:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	73	theme	bacterial	467:475	arg1	toxins					477:482	two related bacterial toxins	455:482	two related bacterial toxins	455:482	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	73	theme	bacterial	467:475	arg1	toxins					496:501	Shiga-like toxins	485:501	Shiga-like toxins (Stxs) 1 and 2	485:516	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	0	74	theme	CRISPR	12:17	arg1	screens					19:25	Genome-wide CRISPR screens	0:25	Genome-wide CRISPR screens for Shiga toxins and ricin	0:52	Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation.
30481169	5	75	theme	protein	938:944	arg1	protein					1021:1027	a poorly characterized four-pass membrane protein	979:1027	a poorly characterized four-pass membrane protein	979:1027	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	75	theme	protein	938:944	arg1	alpha					962:966	lysosomal-associated protein transmembrane 4 alpha	917:966	lysosomal-associated protein transmembrane 4 alpha (LAPTM4A)	917:976	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	75	theme	protein	938:944	arg1	factor					1035:1040	a factor	1033:1040	a factor specifically required for Stxs	1033:1071	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	75	theme	protein	938:944	arg1	LAPTM4A					969:975	LAPTM4A	969:975	LAPTM4A	969:975	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	11	76	theme	therapeutic	2119:2129	arg1	targets					2131:2137	novel therapeutic targets	2113:2137	novel therapeutic targets for blocking Stxs and ricin toxicity	2113:2174	These studies reveal key Golgi proteins critical for regulating glycosylation and glycolipid synthesis and provide novel therapeutic targets for blocking Stxs and ricin toxicity.
30481169	9	77	from	general	1902:1908	arg1	levels					1875:1880	proper levels	1868:1880	proper levels of glycosylation in general	1868:1908	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	5	78	theme	membrane	1012:1019	arg1	protein					1021:1027	a poorly characterized four-pass membrane protein	979:1027	a poorly characterized four-pass membrane protein	979:1027	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	78	theme	membrane	1012:1019	arg1	alpha					962:966	lysosomal-associated protein transmembrane 4 alpha	917:966	lysosomal-associated protein transmembrane 4 alpha (LAPTM4A)	917:976	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	9	79	theme	other	1792:1796	arg1	glycosphingolipids					1798:1815	other glycosphingolipids	1792:1815	not only Gb3 but also other glycosphingolipids	1770:1815	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	9	80	from	glycosylation	1885:1897	arg1	general					1902:1908	general	1902:1908	general	1902:1908	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	3	81	theme	toxin	609:613	arg1	ricin					615:619	the plant toxin ricin	599:619	the plant toxin ricin	599:619	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	9	82	theme	KO	1734:1735	arg1	cells					1737:1741	TMEM165 KO and TM9SF2 KO cells	1712:1741	cells	1737:1741	TMEM165 KO and TM9SF2 KO cells both showed a reduction in not only Gb3 but also other glycosphingolipids, suggesting that they are required for maintaining proper levels of glycosylation in general in the Golgi.
30481169	3	83	theme	genome-wide	412:422	arg1	screens					441:447	genome-wide loss-of-function screens	412:447	genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors,	412:593	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	3	84	theme	broad	641:645	arg1	range					647:651	a broad range	639:651	a broad range of glycans	639:662	Here, we carried out Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-mediated genome-wide loss-of-function screens using two related bacterial toxins, Shiga-like toxins (Stxs) 1 and 2, which use a specific glycolipid, globotriaosylceramide (Gb3), as receptors, and the plant toxin ricin, which recognizes a broad range of glycans.
30481169	8	85	theme	Transmembrane	1573:1585	arg1	protein					1587:1593	Transmembrane protein 165	1573:1597	Transmembrane protein 165 (TMEM165)	1573:1607	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	85	theme	Transmembrane	1573:1585	arg1	TMEM165					1600:1606	TMEM165	1600:1606	TMEM165	1600:1606	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	85	theme	Transmembrane	1573:1585	arg1	proteins					1563:1570	two Golgi proteins	1553:1570	two Golgi proteins	1553:1570	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	4	86	theme	Gb3	755:757	arg1	biosynthesis					759:770	Gb3 biosynthesis	755:770	Gb3 biosynthesis	755:770	The Stxs screens identified major glycosyltransferases (GTs) and transporters involved in Gb3 biosynthesis, while the ricin screen identified GTs and transporters involved in N-linked protein glycosylation and fucosylation.
30481169	8	87	theme	member	1641:1646	arg1	TM9SF2					1651:1656	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	Transmembrane 9 superfamily member 2 (TM9SF2)	1613:1657	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	8	87	theme	member	1641:1646	arg1	proteins					1563:1570	two Golgi proteins	1553:1570	two Golgi proteins	1553:1570	These screens also revealed two Golgi proteins, Transmembrane protein 165 (TMEM165) and Transmembrane 9 superfamily member 2 (TM9SF2), as shared factors required for both Stxs and ricin.
30481169	5	88	theme	characterized	988:1000	arg1	protein					1021:1027	a poorly characterized four-pass membrane protein	979:1027	a poorly characterized four-pass membrane protein	979:1027	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	5	88	theme	characterized	988:1000	arg1	alpha					962:966	lysosomal-associated protein transmembrane 4 alpha	917:966	lysosomal-associated protein transmembrane 4 alpha (LAPTM4A)	917:976	The screens also identified lysosomal-associated protein transmembrane 4 alpha (LAPTM4A), a poorly characterized four-pass membrane protein, as a factor specifically required for Stxs.
30481169	6	89	theme	glycolipids	1104:1114	arg1	analysis					1092:1099	Mass spectrometry analysis	1074:1099	Mass spectrometry analysis of glycolipids and their precursors	1074:1135	Mass spectrometry analysis of glycolipids and their precursors demonstrates that LAPTM4A knockout (KO) cells lack Gb3 biosynthesis.
30481169	10	90	theme	endosomal	1975:1983	arg1	trafficking					1985:1995	defective endosomal trafficking	1965:1995	defective endosomal trafficking	1965:1995	In addition, TM9SF2 KO cells also showed defective endosomal trafficking.
27388694	5	0	theme	low	779:781	arg1	titers					865:870	low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers	779:870	low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination	779:922	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	4	1	theme	lower	696:700	arg1	expenditure					732:742	lower than predicted resting energy expenditure	696:742	lower than predicted resting energy expenditure	696:742	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	1	2	dep	PURPOSE	89:95	arg1	catalyzes					151:159	catalyzes	151:159	catalyzes	151:159	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	5	3	theme	laboratory	751:760	arg1	findings					762:769	Novel laboratory findings	745:769	Novel laboratory findings	745:769	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	0	4	theme	deglycosylation	72:86	arg1	disorder					60:67	the first congenital disorder	39:67	the first congenital disorder of deglycosylation	39:86	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	0	4	theme	deglycosylation	72:86	arg1	phenotyping					12:22	Prospective phenotyping	0:22	Prospective phenotyping of NGLY1-CDDG	0:36	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	1	5	link	N-linked	210:217	arg1	glycoproteins					219:231	N-linked glycoproteins	210:231	N-linked glycoproteins	210:231	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	6	6	theme	delay	1157:1161	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	6	theme	delay	1157:1161	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	6	theme	delay	1157:1161	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	6	theme	delay	1157:1161	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	6	theme	delay	1157:1161	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	6	theme	delay	1157:1161	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	7	theme	decreased	1007:1015	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	7	theme	decreased	1007:1015	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	7	theme	decreased	1007:1015	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	7	theme	decreased	1007:1015	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	7	theme	decreased	1007:1015	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	7	theme	decreased	1007:1015	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	7	8	theme	prognostic	1328:1337	arg1	information					1339:1349	prognostic information	1328:1349	prognostic information	1328:1349	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	6	9	theme	varying	1117:1123	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	9	theme	varying	1117:1123	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	9	theme	varying	1117:1123	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	9	theme	varying	1117:1123	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	9	theme	varying	1117:1123	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	9	theme	varying	1117:1123	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	10	with	delay	1157:1161	arg1	socialization					1189:1201	relatively preserved socialization	1168:1201	relatively preserved socialization	1168:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	5	11	theme	Novel	745:749	arg1	findings					762:769	Novel laboratory findings	745:769	Novel laboratory findings	745:769	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	1	12	gly	glycoproteins	219:231	arg1	glycoproteins					219:231	N-linked glycoproteins	210:231	N-linked glycoproteins	210:231	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	4	13	theme	optic	592:596	arg1	atrophy					598:604	optic atrophy	592:604	optic atrophy	592:604	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	7	14	theme	prospective	1252:1262	arg1	phenotyping					1264:1274	Our prospective phenotyping	1248:1274	Our prospective phenotyping	1248:1274	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	7	15	theme	baseline	1365:1372	arg1	data					1374:1377	baseline data	1365:1377	baseline data	1365:1377	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	6	16	theme	consistent	1216:1225	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	16	theme	consistent	1216:1225	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	16	theme	consistent	1216:1225	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	16	theme	consistent	1216:1225	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	16	theme	consistent	1216:1225	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	16	theme	consistent	1216:1225	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	2	17	theme	NGLY1	350:354	arg1	NGLY1-CDDG					368:377	NGLY1-CDDG	368:377	NGLY1-CDDG	368:377	In this study, we describe the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG).
27388694	2	17	theme	NGLY1	350:354	arg1	deficiency					356:365	NGLY1 deficiency	350:365	NGLY1 deficiency (NGLY1-CDDG)	350:378	In this study, we describe the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG).
27388694	4	18	dep	individuals	441:451	arg1	ages					453:456	ages	453:456	ages	453:456	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	5	19	theme	cerebral	783:790	arg1	CSF					806:808	CSF	806:808	CSF	806:808	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	5	19	theme	cerebral	783:790	arg1	fluid					799:803	cerebral spinal fluid	783:803	cerebral spinal fluid (CSF) total protein	783:823	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	4	20	theme	changes/cone	629:640	arg1	dystrophy					642:650	retinal pigmentary changes/cone dystrophy	610:650	retinal pigmentary changes/cone dystrophy	610:650	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	6	21	theme	small	1059:1063	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	21	theme	small	1059:1063	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	21	theme	small	1059:1063	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	21	theme	small	1059:1063	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	21	theme	small	1059:1063	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	21	theme	small	1059:1063	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	4	22	with	ages	453:456	arg1	mutations					516:524	confirmed, biallelic, pathogenic NGLY1 mutations	477:524	confirmed, biallelic, pathogenic NGLY1 mutations	477:524	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	5	23	theme	antibody	856:863	arg1	titers					865:870	low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers	779:870	low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination	779:922	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	0	24	theme	first	43:47	arg1	disorder					60:67	the first congenital disorder	39:67	the first congenital disorder of deglycosylation	39:86	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	0	24	theme	first	43:47	arg1	phenotyping					12:22	Prospective phenotyping	0:22	Prospective phenotyping of NGLY1-CDDG	0:36	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	4	25	theme	confirmed	477:485	arg1	mutations					516:524	confirmed, biallelic, pathogenic NGLY1 mutations	477:524	confirmed, biallelic, pathogenic NGLY1 mutations	477:524	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	5	26	theme	spinal	792:797	arg1	CSF					806:808	CSF	806:808	CSF	806:808	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	5	26	theme	spinal	792:797	arg1	fluid					799:803	cerebral spinal fluid	783:803	cerebral spinal fluid (CSF) total protein	783:823	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	5	27	theme	total	811:815	arg1	protein					817:823	cerebral spinal fluid (CSF) total protein	783:823	cerebral spinal fluid (CSF) total protein	783:823	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	4	28	theme	bone	661:664	arg1	age					666:668	delayed bone age	653:668	delayed bone age	653:668	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	29	dep	21	463:464	arg1	to					460:461	to	460:461	to	460:461	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	6	30	theme	movement	1094:1101	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	30	theme	movement	1094:1101	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	30	theme	movement	1094:1101	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	30	theme	movement	1094:1101	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	30	theme	movement	1094:1101	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	30	theme	movement	1094:1101	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	4	31	theme	joint	671:675	arg1	hypermobility					677:689	joint hypermobility	671:689	joint hypermobility	671:689	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	0	32	theme	Prospective	0:10	arg1	disorder					60:67	the first congenital disorder	39:67	the first congenital disorder of deglycosylation	39:86	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	0	32	theme	Prospective	0:10	arg1	phenotyping					12:22	Prospective phenotyping	0:22	Prospective phenotyping of NGLY1-CDDG	0:36	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	4	33	dep	confirmed	477:485	arg1	biallelic					488:496	biallelic	488:496	biallelic	488:496	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	33	dep	confirmed	477:485	arg1	pathogenic					499:508	pathogenic	499:508	pathogenic	499:508	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	1	34	theme	β-aspartyl	177:186	arg1	bond					202:205	the β-aspartyl glycosylamine bond	173:205	the β-aspartyl glycosylamine bond of N-linked glycoproteins	173:231	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	0	35	theme	NGLY1-CDDG	27:36	arg1	disorder					60:67	the first congenital disorder	39:67	the first congenital disorder of deglycosylation	39:86	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	0	35	theme	NGLY1-CDDG	27:36	arg1	phenotyping					12:22	Prospective phenotyping	0:22	Prospective phenotyping of NGLY1-CDDG	0:36	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	5	36	dep	low	779:781	arg1	albumin					829:835	albumin	829:835	albumin	829:835	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	5	36	dep	low	779:781	arg1	protein					817:823	cerebral spinal fluid (CSF) total protein	783:823	cerebral spinal fluid (CSF) total protein	783:823	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	1	37	theme	cytosolic	101:109	arg1	N-glycanase					118:128	The cytosolic enzyme N-glycanase 1	97:130	The cytosolic enzyme N-glycanase 1	97:130	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	1	38	theme	glycosylamine	188:200	arg1	bond					202:205	the β-aspartyl glycosylamine bond	173:205	the β-aspartyl glycosylamine bond of N-linked glycoproteins	173:231	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	6	39	theme	global	1136:1141	arg1	delay					1157:1161	global developmental delay	1136:1161	global developmental delay with relatively preserved socialization	1136:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	4	40	theme	clinical	563:570	arg1	dystrophy					642:650	retinal pigmentary changes/cone dystrophy	610:650	retinal pigmentary changes/cone dystrophy	610:650	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	40	theme	clinical	563:570	arg1	hypermobility					677:689	joint hypermobility	671:689	joint hypermobility	671:689	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	40	theme	clinical	563:570	arg1	atrophy					598:604	optic atrophy	592:604	optic atrophy	592:604	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	40	theme	clinical	563:570	arg1	expenditure					732:742	lower than predicted resting energy expenditure	696:742	lower than predicted resting energy expenditure	696:742	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	40	theme	clinical	563:570	arg1	age					666:668	delayed bone age	653:668	delayed bone age	653:668	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	40	theme	clinical	563:570	arg1	features					572:579	previously unreported clinical features	541:579	previously unreported clinical features	541:579	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	1	41	theme	enzyme	111:116	arg1	N-glycanase					118:128	The cytosolic enzyme N-glycanase 1	97:130	The cytosolic enzyme N-glycanase 1	97:130	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	1	42	theme	bond	202:205	arg1	cleavage					161:168	cleavage	161:168	cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins	161:231	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	3	43	theme	history	409:415	arg1	protocol					417:424	Prospective natural history protocol	389:424	Prospective natural history protocol	389:424	METHODS Prospective natural history protocol.
27388694	4	44	theme	unreported	552:561	arg1	dystrophy					642:650	retinal pigmentary changes/cone dystrophy	610:650	retinal pigmentary changes/cone dystrophy	610:650	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	44	theme	unreported	552:561	arg1	hypermobility					677:689	joint hypermobility	671:689	joint hypermobility	671:689	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	44	theme	unreported	552:561	arg1	atrophy					598:604	optic atrophy	592:604	optic atrophy	592:604	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	44	theme	unreported	552:561	arg1	expenditure					732:742	lower than predicted resting energy expenditure	696:742	lower than predicted resting energy expenditure	696:742	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	44	theme	unreported	552:561	arg1	age					666:668	delayed bone age	653:668	delayed bone age	653:668	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	4	44	theme	unreported	552:561	arg1	features					572:579	previously unreported clinical features	541:579	previously unreported clinical features	541:579	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	6	45	theme	reported	977:984	arg1	findings					986:993	previously reported findings	966:993	previously reported findings	966:993	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	46	theme	hyperkinetic	1081:1092	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	46	theme	hyperkinetic	1081:1092	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	46	theme	hyperkinetic	1081:1092	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	46	theme	hyperkinetic	1081:1092	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	46	theme	hyperkinetic	1081:1092	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	46	theme	hyperkinetic	1081:1092	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	4	47	theme	delayed	653:659	arg1	age					666:668	delayed bone age	653:668	delayed bone age	653:668	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	5	48	theme	fluid	799:803	arg1	protein					817:823	cerebral spinal fluid (CSF) total protein	783:823	cerebral spinal fluid (CSF) total protein	783:823	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	4	49	theme	than	702:705	arg1	expenditure					732:742	lower than predicted resting energy expenditure	696:742	lower than predicted resting energy expenditure	696:742	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	6	50	theme	transient	1034:1042	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	50	theme	transient	1034:1042	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	50	theme	transient	1034:1042	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	50	theme	transient	1034:1042	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	50	theme	transient	1034:1042	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	50	theme	transient	1034:1042	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	1	51	theme	N-linked	210:217	arg1	glycoproteins					219:231	N-linked glycoproteins	210:231	N-linked glycoproteins	210:231	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	3	52	theme	Prospective	389:399	arg1	protocol					417:424	Prospective natural history protocol	389:424	Prospective natural history protocol	389:424	METHODS Prospective natural history protocol.
27388694	4	53	theme	NGLY1	510:514	arg1	mutations					516:524	confirmed, biallelic, pathogenic NGLY1 mutations	477:524	confirmed, biallelic, pathogenic NGLY1 mutations	477:524	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	7	54	theme	clinical	1288:1295	arg1	spectrum					1297:1304	the clinical spectrum	1284:1304	the clinical spectrum of NGLY1-CDDG	1284:1318	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	4	55	theme	predicted	707:715	arg1	expenditure					732:742	lower than predicted resting energy expenditure	696:742	lower than predicted resting energy expenditure	696:742	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	3	56	theme	natural	401:407	arg1	protocol					417:424	Prospective natural history protocol	389:424	Prospective natural history protocol	389:424	METHODS Prospective natural history protocol.
27388694	7	57	dep	CONCLUSION	1237:1246	arg1	expands					1276:1282	expands	1276:1282	expands	1276:1282	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	7	57	dep	CONCLUSION	1237:1246	arg1	provides					1356:1363	provides	1356:1363	provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168	1356:1442	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	7	57	dep	CONCLUSION	1237:1246	arg1	offers					1321:1326	offers	1321:1326	offers prognostic information	1321:1349	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	6	58	theme	tear	1017:1020	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	58	theme	tear	1017:1020	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	58	theme	tear	1017:1020	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	58	theme	tear	1017:1020	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	58	theme	tear	1017:1020	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	58	theme	tear	1017:1020	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	2	59	theme	clinical	329:336	arg1	spectrum					338:345	the clinical spectrum	325:345	the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG)	325:378	In this study, we describe the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG).
27388694	4	60	from	RESULTS	427:433	arg1	individuals					441:451	12 individuals	438:451	12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations	438:524	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	7	61	theme	therapeutic	1394:1404	arg1	Med					1426:1428	therapeutic interventions.Genet Med 19	1394:1431	therapeutic interventions.Genet Med 19 2	1394:1433	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	7	61	theme	therapeutic	1394:1404	arg1	160-168					1436:1442	160-168	1436:1442	160-168	1436:1442	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	4	62	theme	energy	725:730	arg1	expenditure					732:742	lower than predicted resting energy expenditure	696:742	lower than predicted resting energy expenditure	696:742	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	6	63	theme	preserved	1179:1187	arg1	socialization					1189:1201	relatively preserved socialization	1168:1201	relatively preserved socialization	1168:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	1	64	theme	glycoproteins	219:231	arg1	bond					202:205	the β-aspartyl glycosylamine bond	173:205	the β-aspartyl glycosylamine bond of N-linked glycoproteins	173:231	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
27388694	4	65	theme	resting	717:723	arg1	expenditure					732:742	lower than predicted resting energy expenditure	696:742	lower than predicted resting energy expenditure	696:742	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	6	66	theme	developmental	1143:1155	arg1	delay					1157:1161	global developmental delay	1136:1161	global developmental delay with relatively preserved socialization	1136:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	5	67	theme	high	851:854	arg1	titers					865:870	low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers	779:870	low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination	779:922	Novel laboratory findings include low cerebral spinal fluid (CSF) total protein and albumin and unusually high antibody titers toward rubella and/or rubeola following vaccination.
27388694	6	68	theme	complex	1073:1079	arg1	production					1022:1031	decreased tear production	1007:1031	decreased tear production	1007:1031	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	68	theme	complex	1073:1079	arg1	feet					1065:1068	small feet	1059:1068	small feet	1059:1068	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	68	theme	complex	1073:1079	arg1	features					1227:1234	the most consistent features	1207:1234	the most consistent features	1207:1234	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	68	theme	complex	1073:1079	arg1	degrees					1125:1131	varying degrees	1117:1131	varying degrees of global developmental delay with relatively preserved socialization	1117:1201	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	68	theme	complex	1073:1079	arg1	transaminitis					1044:1056	transient transaminitis	1034:1056	transient transaminitis	1034:1056	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	6	68	theme	complex	1073:1079	arg1	disorder					1103:1110	a complex hyperkinetic movement disorder	1071:1110	a complex hyperkinetic movement disorder	1071:1110	We also confirmed and further quantified previously reported findings noting that decreased tear production, transient transaminitis, small feet, a complex hyperkinetic movement disorder, and varying degrees of global developmental delay with relatively preserved socialization are the most consistent features.
27388694	7	69	theme	NGLY1-CDDG	1309:1318	arg1	spectrum					1297:1304	the clinical spectrum	1284:1304	the clinical spectrum of NGLY1-CDDG	1284:1318	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	7	70	theme	interventions.Genet	1406:1424	arg1	Med					1426:1428	therapeutic interventions.Genet Med 19	1394:1431	therapeutic interventions.Genet Med 19 2	1394:1433	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	7	70	theme	interventions.Genet	1406:1424	arg1	160-168					1436:1442	160-168	1436:1442	160-168	1436:1442	CONCLUSION Our prospective phenotyping expands the clinical spectrum of NGLY1-CDDG, offers prognostic information, and provides baseline data for evaluating therapeutic interventions.Genet Med 19 2, 160-168.
27388694	4	71	theme	pigmentary	618:627	arg1	dystrophy					642:650	retinal pigmentary changes/cone dystrophy	610:650	retinal pigmentary changes/cone dystrophy	610:650	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	0	72	theme	congenital	49:58	arg1	disorder					60:67	the first congenital disorder	39:67	the first congenital disorder of deglycosylation	39:86	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	0	72	theme	congenital	49:58	arg1	phenotyping					12:22	Prospective phenotyping	0:22	Prospective phenotyping of NGLY1-CDDG	0:36	Prospective phenotyping of NGLY1-CDDG, the first congenital disorder of deglycosylation.
27388694	4	73	theme	retinal	610:616	arg1	dystrophy					642:650	retinal pigmentary changes/cone dystrophy	610:650	retinal pigmentary changes/cone dystrophy	610:650	RESULTS In 12 individuals ages 2 to 21 years with confirmed, biallelic, pathogenic NGLY1 mutations, we identified previously unreported clinical features, including optic atrophy and retinal pigmentary changes/cone dystrophy, delayed bone age, joint hypermobility, and lower than predicted resting energy expenditure.
27388694	2	74	theme	deficiency	356:365	arg1	spectrum					338:345	the clinical spectrum	325:345	the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG)	325:378	In this study, we describe the clinical spectrum of NGLY1 deficiency (NGLY1-CDDG).
27388694	1	75	theme	intact	244:249	arg1	N-glycans					251:259	intact N-glycans	244:259	intact N-glycans	244:259	PURPOSE The cytosolic enzyme N-glycanase 1, encoded by NGLY1, catalyzes cleavage of the β-aspartyl glycosylamine bond of N-linked glycoproteins, releasing intact N-glycans from proteins bound for degradation.
31199881	4	0	theme	plasma	778:783	arg1	clearance					785:793	plasma clearance	778:793	plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO,	778:846	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	8	1	dep	11-fold	1554:1560	arg1	to					1551:1552	to	1551:1552	to	1551:1552	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	8	2	theme	wild-type	1432:1440	arg1	proteins					1471:1478	both the wild-type and mutant TfRMAb-EPO fusion proteins	1423:1478	proteins	1471:1478	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	3	3	theme	N-linked	614:621	arg1	site					637:640	the Fc N-linked glycosylation site	607:640	the Fc N-linked glycosylation site	607:640	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	6	4	theme	Plasma	1128:1133	arg1	PK					1135:1136	Plasma PK	1128:1136	Plasma PK	1128:1136	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	1	5	theme	blood-brain	243:253	arg1	BBB					264:266	BBB	264:266	BBB	264:266	Erythropoietin (EPO) is a potential therapeutic for Alzheimer's disease (AD); however, limited blood-brain barrier (BBB) penetration reduces its applicability as a CNS therapeutic.
31199881	1	5	theme	blood-brain	243:253	arg1	barrier					255:261	blood-brain barrier	243:261	limited blood-brain barrier (BBB) penetration	235:279	Erythropoietin (EPO) is a potential therapeutic for Alzheimer's disease (AD); however, limited blood-brain barrier (BBB) penetration reduces its applicability as a CNS therapeutic.
31199881	11	6	theme	SQ	2201:2202	arg1	administration					2204:2217	SQ administration	2201:2217	SQ administration	2201:2217	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	2	7	theme	AD	540:541	arg1	model					531:535	a mouse model	523:535	a mouse model of AD	523:541	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	11	8	theme	plasma	2132:2137	arg1	route					2243:2247	the preferred route	2229:2247	the preferred route of administration in humans for chronic neurodegenerative diseases including AD	2229:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	8	theme	plasma	2132:2137	arg1	levels					2139:2144	the plasma levels	2128:2144	the plasma levels	2128:2144	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	8	9	theme	mutant	1446:1451	arg1	proteins					1471:1478	both the wild-type and mutant TfRMAb-EPO fusion proteins	1423:1478	proteins	1471:1478	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	8	10	theme	10-fold	1509:1515	arg1	increase					1517:1524	a 10-fold increase	1507:1524	a 10-fold increase in dose	1507:1532	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	7	11	theme	profound	1268:1275	arg1	increase					1277:1284	a profound increase	1266:1284	a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO	1266:1336	The results show a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO compared with the wild-type TfRMAb-EPO following IV administration.
31199881	8	12	from	decrease	1562:1569	arg1	clearance					1581:1589	plasma clearance	1574:1589	plasma clearance	1574:1589	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	9	13	theme	IP	1602:1603	arg1	administration					1612:1625	IP and SQ administration	1602:1625	IP and SQ administration	1602:1625	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	1	14	theme	therapeutic	184:194	arg1	Erythropoietin					148:161	Erythropoietin	148:161	Erythropoietin (EPO)	148:167	Erythropoietin (EPO) is a potential therapeutic for Alzheimer's disease (AD); however, limited blood-brain barrier (BBB) penetration reduces its applicability as a CNS therapeutic.
31199881	1	14	theme	therapeutic	184:194	arg1	potential					174:182	a potential therapeutic	172:194	a potential therapeutic for Alzheimer's disease (AD)	172:223	Erythropoietin (EPO) is a potential therapeutic for Alzheimer's disease (AD); however, limited blood-brain barrier (BBB) penetration reduces its applicability as a CNS therapeutic.
31199881	2	15	theme	mouse	525:529	arg1	model					531:535	a mouse model	523:535	a mouse model of AD	523:541	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	3	16	theme	Fc	683:684	arg1	function					695:702	the Fc effector function	679:702	the Fc effector function	679:702	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	5	17	theme	IgG1	944:947	arg1	chain					964:968	the mouse IgG1 constant heavy chain	934:968	the mouse IgG1 constant heavy chain region	934:975	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	7	18	from	increase	1277:1284	arg1	8-fold					1306:1311	8-fold	1306:1311	8-fold	1306:1311	The results show a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO compared with the wild-type TfRMAb-EPO following IV administration.
31199881	7	18	from	increase	1277:1284	arg1	clearance					1289:1297	clearance	1289:1297	clearance (6- to 8-fold) of the TfRMAb-N292G-EPO	1289:1336	The results show a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO compared with the wild-type TfRMAb-EPO following IV administration.
31199881	5	19	theme	heavy	958:962	arg1	chain					964:968	the mouse IgG1 constant heavy chain	934:968	the mouse IgG1 constant heavy chain region	934:975	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	11	20	from	humans	2270:2275	arg1	levels					2139:2144	the plasma levels	2128:2144	the plasma levels	2128:2144	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	20	from	humans	2270:2275	arg1	route					2243:2247	the preferred route	2229:2247	the preferred route of administration in humans for chronic neurodegenerative diseases including AD	2229:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	4	21	theme	fusion	811:816	arg1	proteins					818:825	TfRMAb-based fusion proteins	798:825	TfRMAb-based fusion proteins	798:825	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	4	21	theme	fusion	811:816	arg1	TfRMAb-EPO					836:845	TfRMAb-EPO	836:845	TfRMAb-EPO	836:845	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	5	22	from	position	1096:1103	arg1	residue					1085:1091	the Asn residue	1077:1091	the Asn residue at position 292	1077:1107	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	3	23	theme	function	569:576	arg1	effects					583:589	Fc effector function side effects	557:589	Fc effector function side effects	557:589	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	8	24	theme	plasma	1574:1579	arg1	clearance					1581:1589	plasma clearance	1574:1589	plasma clearance	1574:1589	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	9	25	dep	reduced	1709:1715	arg1	37-					1692:1694	37-	1692:1694	37-	1692:1694	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	2	26	theme	EPO	467:469	arg1	protective					509:518	protective	509:518	protective	509:518	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	26	theme	EPO	467:469	arg1	protein					456:462	a fusion protein	447:462	a fusion protein	447:462	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	8	27	dep	proteins	1471:1478	arg1	both					1423:1426	both	1423:1426	both	1423:1426	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	7	28	dep	8-fold	1306:1311	arg1	to					1303:1304	to	1303:1304	to	1303:1304	The results show a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO compared with the wild-type TfRMAb-EPO following IV administration.
31199881	5	29	theme	Asn	994:996	arg1	residue					998:1004	the Asn residue	990:1004	the Asn residue at position 292	990:1020	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	3	30	theme	Fc	557:558	arg1	effects					583:589	Fc effector function side effects	557:589	Fc effector function side effects	557:589	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	4	31	from	effect	718:723	arg1	PK					771:772	PK	771:772	PK	771:772	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	4	31	from	effect	718:723	arg1	pharmacokinetics					753:768	the pharmacokinetics	749:768	the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO,	749:846	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	11	32	theme	beneficial	2000:2009	arg1	suppression					2011:2021	the beneficial suppression	1996:2021	the beneficial suppression of effector function via the N292G mutation	1996:2065	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	33	theme	preferred	2233:2241	arg1	levels					2139:2144	the plasma levels	2128:2144	the plasma levels	2128:2144	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	33	theme	preferred	2233:2241	arg1	route					2243:2247	the preferred route	2229:2247	the preferred route of administration in humans for chronic neurodegenerative diseases including AD	2229:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	34	theme	protein	2171:2177	arg1	route					2243:2247	the preferred route	2229:2247	the preferred route of administration in humans for chronic neurodegenerative diseases including AD	2229:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	34	theme	protein	2171:2177	arg1	levels					2139:2144	the plasma levels	2128:2144	the plasma levels	2128:2144	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	6	35	from	administration	1176:1189	arg1	mice					1243:1246	adult male C57 mice	1228:1246	adult male C57 mice	1228:1246	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	2	36	theme	TfRMAb	475:480	arg1	protective					509:518	protective	509:518	protective	509:518	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	36	theme	TfRMAb	475:480	arg1	protein					456:462	a fusion protein	447:462	a fusion protein	447:462	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	11	37	theme	TfRMAb-EPO	2153:2162	arg1	protein					2171:2177	the TfRMAb-EPO fusion protein	2149:2177	the TfRMAb-EPO fusion protein	2149:2177	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	0	38	theme	Attenuation	127:137	arg1	Function					106:113	a Function	104:113	a Function of Effector Attenuation in Mice	104:145	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	0	38	theme	Attenuation	127:137	arg1	Pharmacokinetics					7:22	Plasma Pharmacokinetics	0:22	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	0:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	0	39	theme	Receptor	53:60	arg1	Protein					93:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	2	40	theme	drug	428:431	arg1	delivery					433:440	brain drug delivery	422:440	brain drug delivery	422:440	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	11	41	theme	neurodegenerative	2289:2305	arg1	AD					2326:2327	AD	2326:2327	AD	2326:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	41	theme	neurodegenerative	2289:2305	arg1	diseases					2307:2314	chronic neurodegenerative diseases	2281:2314	chronic neurodegenerative diseases including AD	2281:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	9	42	theme	fusion	1821:1826	arg1	protein					1828:1834	the mutant fusion protein	1810:1834	the mutant fusion protein	1810:1834	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	11	43	from	route	2243:2247	arg1	humans					2270:2275	humans	2270:2275	humans	2270:2275	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	0	44	theme	Plasma	0:5	arg1	Function					106:113	a Function	104:113	a Function of Effector Attenuation in Mice	104:145	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	0	44	theme	Plasma	0:5	arg1	Pharmacokinetics					7:22	Plasma Pharmacokinetics	0:22	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	0:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	6	45	from	IP	1165:1166	arg1	mice					1243:1246	adult male C57 mice	1228:1246	adult male C57 mice	1228:1246	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	2	46	theme	Trojan	404:409	arg1	horses					411:416	molecular Trojan horses	394:416	molecular Trojan horses for brain drug delivery	394:440	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	46	theme	Trojan	404:409	arg1	Antibodies					329:338	Antibodies	329:338	Antibodies against the BBB transferrin receptor (TfRMAbs)	329:385	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	6	47	theme	C57	1239:1241	arg1	mice					1243:1246	adult male C57 mice	1228:1246	adult male C57 mice	1228:1246	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	5	48	theme	mutant	1043:1048	arg1	TfRMAb-N292G-EPO					1050:1065	the mutant TfRMAb-N292G-EPO	1039:1065	the mutant TfRMAb-N292G-EPO	1039:1065	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	7	49	theme	TfRMAb-N292G-EPO	1321:1336	arg1	8-fold					1306:1311	8-fold	1306:1311	8-fold	1306:1311	The results show a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO compared with the wild-type TfRMAb-EPO following IV administration.
31199881	7	49	theme	TfRMAb-N292G-EPO	1321:1336	arg1	clearance					1289:1297	clearance	1289:1297	clearance (6- to 8-fold) of the TfRMAb-N292G-EPO	1289:1336	The results show a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO compared with the wild-type TfRMAb-EPO following IV administration.
31199881	4	50	theme	mutations	736:744	arg1	effect					718:723	the effect	714:723	the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO,	714:846	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	4	50	theme	mutations	736:744	arg1	unknown					851:857	unknown	851:857	unknown	851:857	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	6	51	theme	adult	1228:1232	arg1	mice					1243:1246	adult male C57 mice	1228:1246	adult male C57 mice	1228:1246	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	0	52	theme	Transferrin	41:51	arg1	Protein					93:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	0	53	theme	Protein	93:99	arg1	Function					106:113	a Function	104:113	a Function of Effector Attenuation in Mice	104:145	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	0	53	theme	Protein	93:99	arg1	Pharmacokinetics					7:22	Plasma Pharmacokinetics	0:22	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	0:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	0	54	theme	Antibody-Erythropoietin	62:84	arg1	Protein					93:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	6	55	from	IV	1161:1162	arg1	mice					1243:1246	adult male C57 mice	1228:1246	adult male C57 mice	1228:1246	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	10	56	theme	fusion	1858:1863	arg1	protein					1865:1871	The wild-type TfRMAb fusion protein	1837:1871	The wild-type TfRMAb fusion protein	1837:1871	The wild-type TfRMAb fusion protein was associated with reticulocyte suppression, and the N292G mutation mitigated this suppression of reticulocytes.
31199881	3	57	theme	Fc	611:612	arg1	site					637:640	the Fc N-linked glycosylation site	607:640	the Fc N-linked glycosylation site	607:640	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	4	58	theme	Fc	733:734	arg1	mutations					736:744	such Fc mutations	728:744	such Fc mutations	728:744	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	8	59	theme	TfRMAb-EPO	1453:1462	arg1	proteins					1471:1478	both the wild-type and mutant TfRMAb-EPO fusion proteins	1423:1478	proteins	1471:1478	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	5	60	theme	Asn	1081:1083	arg1	residue					1085:1091	the Asn residue	1077:1091	the Asn residue at position 292	1077:1107	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	10	61	theme	wild-type	1841:1849	arg1	protein					1865:1871	The wild-type TfRMAb fusion protein	1837:1871	The wild-type TfRMAb fusion protein	1837:1871	The wild-type TfRMAb fusion protein was associated with reticulocyte suppression, and the N292G mutation mitigated this suppression of reticulocytes.
31199881	3	62	contain	have	552:555	arg1	TfRMAbs					544:550	TfRMAbs	544:550	TfRMAbs	544:550	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	3	62	contain	have	552:555	arg2	effects					583:589	Fc effector function side effects	557:589	Fc effector function side effects	557:589	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	4	63	theme	such	728:731	arg1	mutations					736:744	such Fc mutations	728:744	such Fc mutations	728:744	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	2	64	theme	transferrin	356:366	arg1	TfRMAbs					378:384	TfRMAbs	378:384	TfRMAbs	378:384	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	64	theme	transferrin	356:366	arg1	receptor					368:375	the BBB transferrin receptor	348:375	the BBB transferrin receptor (TfRMAbs)	348:385	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	8	65	theme	proteins	1471:1478	arg1	clearance					1410:1418	The clearance	1406:1418	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins	1406:1478	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	5	66	theme	TfRMAb-EPO	894:903	arg1	PK					888:889	the plasma PK	877:889	the plasma PK	877:889	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	2	67	from	model	531:535	arg1	protective					509:518	protective	509:518	protective	509:518	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	67	from	model	531:535	arg1	protein					456:462	a fusion protein	447:462	a fusion protein	447:462	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	9	68	theme	comparable	1766:1775	arg1	increases					1777:1785	comparable increases	1766:1785	comparable increases in plasma clearance of the mutant fusion protein	1766:1834	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	11	69	dep	effect	2100:2105	arg1	has					2121:2123	has	2121:2123	has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD	2121:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	8	70	theme	nonlinear	1489:1497	arg1	PK					1499:1500	nonlinear PK	1489:1500	nonlinear PK	1489:1500	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	1	71	theme	limited	235:241	arg1	penetration					269:279	limited blood-brain barrier (BBB) penetration	235:279	limited blood-brain barrier (BBB) penetration	235:279	Erythropoietin (EPO) is a potential therapeutic for Alzheimer's disease (AD); however, limited blood-brain barrier (BBB) penetration reduces its applicability as a CNS therapeutic.
31199881	3	72	theme	glycosylation	623:635	arg1	site					637:640	the Fc N-linked glycosylation site	607:640	the Fc N-linked glycosylation site	607:640	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	1	73	theme	barrier	255:261	arg1	penetration					269:279	limited blood-brain barrier (BBB) penetration	235:279	limited blood-brain barrier (BBB) penetration	235:279	Erythropoietin (EPO) is a potential therapeutic for Alzheimer's disease (AD); however, limited blood-brain barrier (BBB) penetration reduces its applicability as a CNS therapeutic.
31199881	4	74	theme	clearance	785:793	arg1	PK					771:772	PK	771:772	PK	771:772	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	4	74	theme	clearance	785:793	arg1	pharmacokinetics					753:768	the pharmacokinetics	749:768	the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO,	749:846	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	10	75	theme	reticulocyte	1893:1904	arg1	suppression					1906:1916	reticulocyte suppression	1893:1916	reticulocyte suppression	1893:1916	The wild-type TfRMAb fusion protein was associated with reticulocyte suppression, and the N292G mutation mitigated this suppression of reticulocytes.
31199881	3	76	link	N-linked	614:621	arg1	site					637:640	the Fc N-linked glycosylation site	607:640	the Fc N-linked glycosylation site	607:640	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	3	77	theme	effector	686:693	arg1	function					695:702	the Fc effector function	679:702	the Fc effector function	679:702	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	11	78	theme	fusion	2164:2169	arg1	protein					2171:2177	the TfRMAb-EPO fusion protein	2149:2177	the TfRMAb-EPO fusion protein	2149:2177	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	0	79	from	Function	106:113	arg1	Mice					142:145	Mice	142:145	Mice	142:145	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	10	80	theme	N292G	1927:1931	arg1	mutation					1933:1940	the N292G mutation	1923:1940	the N292G mutation	1923:1940	The wild-type TfRMAb fusion protein was associated with reticulocyte suppression, and the N292G mutation mitigated this suppression of reticulocytes.
31199881	11	81	theme	deleterious	2088:2098	arg1	effect					2100:2105	the deleterious effect	2084:2105	the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD	2084:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	5	82	theme	constant	949:956	arg1	chain					964:968	the mouse IgG1 constant heavy chain	934:968	the mouse IgG1 constant heavy chain region	934:975	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	9	83	theme	wild-type	1735:1743	arg1	TfRMAb-EPO					1745:1754	the wild-type TfRMAb-EPO	1731:1754	the wild-type TfRMAb-EPO	1731:1754	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	5	84	dep	PK	888:889	arg1	wild-type					906:914	wild-type	906:914	wild-type	906:914	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	5	85	theme	chain	964:968	arg1	region					970:975	the mouse IgG1 constant heavy chain region	934:975	the mouse IgG1 constant heavy chain region	934:975	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	4	86	theme	TfRMAb-based	798:809	arg1	proteins					818:825	TfRMAb-based fusion proteins	798:825	TfRMAb-based fusion proteins	798:825	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	4	86	theme	TfRMAb-based	798:809	arg1	TfRMAb-EPO					836:845	TfRMAb-EPO	836:845	TfRMAb-EPO	836:845	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	3	87	theme	effector	560:567	arg1	effects					583:589	Fc effector function side effects	557:589	Fc effector function side effects	557:589	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	8	88	theme	11-fold	1554:1560	arg1	decrease					1562:1569	a 7- to 11-fold decrease	1546:1569	a 7- to 11-fold decrease in plasma clearance	1546:1589	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	4	89	theme	proteins	818:825	arg1	clearance					785:793	plasma clearance	778:793	plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO,	778:846	However, the effect of such Fc mutations on the pharmacokinetics (PK) of plasma clearance of TfRMAb-based fusion proteins, such as TfRMAb-EPO, is unknown.
31199881	5	90	theme	mouse	938:942	arg1	chain					964:968	the mouse IgG1 constant heavy chain	934:968	the mouse IgG1 constant heavy chain region	934:975	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	11	91	theme	effector	2026:2033	arg1	function					2035:2042	effector function	2026:2042	effector function	2026:2042	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	7	92	theme	wild-type	1356:1364	arg1	TfRMAb-EPO					1366:1375	the wild-type TfRMAb-EPO	1352:1375	the wild-type TfRMAb-EPO following IV administration	1352:1403	The results show a profound increase in clearance (6- to 8-fold) of the TfRMAb-N292G-EPO compared with the wild-type TfRMAb-EPO following IV administration.
31199881	2	93	theme	fusion	449:454	arg1	protective					509:518	protective	509:518	protective	509:518	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	93	theme	fusion	449:454	arg1	protein					456:462	a fusion protein	447:462	a fusion protein	447:462	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	11	94	theme	administration	2252:2265	arg1	levels					2139:2144	the plasma levels	2128:2144	the plasma levels	2128:2144	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	94	theme	administration	2252:2265	arg1	route					2243:2247	the preferred route	2229:2247	the preferred route of administration in humans for chronic neurodegenerative diseases including AD	2229:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	9	95	theme	plasma	1790:1795	arg1	clearance					1797:1805	plasma clearance	1790:1805	plasma clearance of the mutant fusion protein	1790:1834	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	0	96	theme	Effector	118:125	arg1	Attenuation					127:137	Effector Attenuation	118:137	Effector Attenuation	118:137	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	11	97	theme	N292G	2052:2056	arg1	mutation					2058:2065	the N292G mutation	2048:2065	the N292G mutation	2048:2065	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	9	98	from	increases	1777:1785	arg1	clearance					1797:1805	plasma clearance	1790:1805	plasma clearance of the mutant fusion protein	1790:1834	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	11	99	theme	chronic	2281:2287	arg1	AD					2326:2327	AD	2326:2327	AD	2326:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	99	theme	chronic	2281:2287	arg1	diseases					2307:2314	chronic neurodegenerative diseases	2281:2314	chronic neurodegenerative diseases including AD	2281:2327	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	11	100	from	administration	2252:2265	arg1	humans					2270:2275	humans	2270:2275	humans	2270:2275	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	9	101	theme	mutant	1814:1819	arg1	protein					1828:1834	the mutant fusion protein	1810:1834	the mutant fusion protein	1810:1834	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	11	102	theme	function	2035:2042	arg1	suppression					2011:2021	the beneficial suppression	1996:2021	the beneficial suppression of effector function via the N292G mutation	1996:2065	Overall, the beneficial suppression of effector function via the N292G mutation may be offset by the deleterious effect this mutation has on the plasma levels of the TfRMAb-EPO fusion protein, especially following SQ administration, which is the preferred route of administration in humans for chronic neurodegenerative diseases including AD.
31199881	2	103	theme	brain	422:426	arg1	delivery					433:440	brain drug delivery	422:440	brain drug delivery	422:440	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	9	104	theme	protein	1828:1834	arg1	clearance					1797:1805	plasma clearance	1790:1805	plasma clearance of the mutant fusion protein	1790:1834	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	0	105	theme	High-Affinity	27:39	arg1	Protein					93:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	9	106	theme	SQ	1609:1610	arg1	administration					1612:1625	IP and SQ administration	1602:1625	IP and SQ administration	1602:1625	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	5	107	from	position	1009:1016	arg1	residue					998:1004	the Asn residue	990:1004	the Asn residue at position 292	990:1020	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	2	108	theme	molecular	394:402	arg1	horses					411:416	molecular Trojan horses	394:416	molecular Trojan horses for brain drug delivery	394:440	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	108	theme	molecular	394:402	arg1	Antibodies					329:338	Antibodies	329:338	Antibodies against the BBB transferrin receptor (TfRMAbs)	329:385	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	6	109	theme	male	1234:1237	arg1	mice					1243:1246	adult male C57 mice	1228:1246	adult male C57 mice	1228:1246	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	3	110	theme	side	578:581	arg1	effects					583:589	Fc effector function side effects	557:589	Fc effector function side effects	557:589	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	8	111	from	increase	1517:1524	arg1	dose					1529:1532	dose	1529:1532	dose	1529:1532	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	6	112	theme	SQ	1173:1174	arg1	administration					1176:1189	SQ administration	1173:1189	SQ administration	1173:1189	Plasma PK was compared following IV, IP, and SQ administration for doses between 0.3 and 3 mg/kg in adult male C57 mice.
31199881	0	113	theme	Fusion	86:91	arg1	Protein					93:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein	27:99	Plasma Pharmacokinetics of High-Affinity Transferrin Receptor Antibody-Erythropoietin Fusion Protein is a Function of Effector Attenuation in Mice.
31199881	9	114	theme	Cmax	1632:1635	arg1	values					1637:1642	the Cmax values	1628:1642	the Cmax values of the TfRMAb-N292G-EPO mutant	1628:1673	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	3	115	gly	glycosylation	623:635	arg2	site					637:640	the Fc N-linked glycosylation site	607:640	the Fc N-linked glycosylation site	607:640	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	8	116	theme	fusion	1464:1469	arg1	proteins					1471:1478	both the wild-type and mutant TfRMAb-EPO fusion proteins	1423:1478	proteins	1471:1478	The clearance of both the wild-type and mutant TfRMAb-EPO fusion proteins followed nonlinear PK, and a 10-fold increase in dose resulted in a 7- to 11-fold decrease in plasma clearance.
31199881	5	117	theme	plasma	881:886	arg1	PK					888:889	the plasma PK	877:889	the plasma PK	877:889	To examine this, the plasma PK of TfRMAb-EPO (wild-type), which expresses the mouse IgG1 constant heavy chain region and includes the Asn residue at position 292, was compared to the mutant TfRMAb-N292G-EPO, in which the Asn residue at position 292 is mutated to Gly.
31199881	10	118	theme	TfRMAb	1851:1856	arg1	protein					1865:1871	The wild-type TfRMAb fusion protein	1837:1871	The wild-type TfRMAb fusion protein	1837:1871	The wild-type TfRMAb fusion protein was associated with reticulocyte suppression, and the N292G mutation mitigated this suppression of reticulocytes.
31199881	10	119	theme	reticulocytes	1972:1984	arg1	suppression					1957:1967	this suppression	1952:1967	this suppression of reticulocytes	1952:1984	The wild-type TfRMAb fusion protein was associated with reticulocyte suppression, and the N292G mutation mitigated this suppression of reticulocytes.
31199881	9	120	theme	mutant	1668:1673	arg1	values					1637:1642	the Cmax values	1628:1642	the Cmax values of the TfRMAb-N292G-EPO mutant	1628:1673	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	9	121	theme	TfRMAb-N292G-EPO	1651:1666	arg1	mutant					1668:1673	the TfRMAb-N292G-EPO mutant	1647:1673	the TfRMAb-N292G-EPO mutant	1647:1673	Following IP and SQ administration, the Cmax values of the TfRMAb-N292G-EPO mutant were profoundly (37- to 114-fold) reduced compared with the wild-type TfRMAb-EPO, owing to comparable increases in plasma clearance of the mutant fusion protein.
31199881	2	122	from	protective	509:518	arg1	model					531:535	a mouse model	523:535	a mouse model of AD	523:541	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	3	123	theme	site	637:640	arg1	removal					596:602	removal	596:602	removal of the Fc N-linked glycosylation site by substituting Asn with Gly	596:669	TfRMAbs have Fc effector function side effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly reduces the Fc effector function.
31199881	2	124	theme	BBB	352:354	arg1	TfRMAbs					378:384	TfRMAbs	378:384	TfRMAbs	378:384	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31199881	2	124	theme	BBB	352:354	arg1	receptor					368:375	the BBB transferrin receptor	348:375	the BBB transferrin receptor (TfRMAbs)	348:385	Antibodies against the BBB transferrin receptor (TfRMAbs) act as molecular Trojan horses for brain drug delivery, and a fusion protein of EPO and TfRMAb, designated TfRMAb-EPO, is protective in a mouse model of AD.
31561469	0	0	theme	Viper	71:75	arg1	atrox					92:96	the Peruvian Pit Viper Snake Bothrops atrox	54:96	the Peruvian Pit Viper Snake Bothrops atrox	54:96	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	14	1	theme	Bothrops	1590:1597	arg1	atrox					1599:1603	Bothrops atrox	1590:1603	Bothrops atrox	1590:1603	Selectively, Atr-III targets GPVI antagonistically and thus contributes to the antithrombotic effect of envenomation by Bothrops atrox.
31561469	10	2	theme	glycoprotein	1146:1157	arg1	GPVI					1163:1166	glycoprotein VI (GPVI)	1146:1167	glycoprotein VI (GPVI)	1146:1167	Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and α2β1 integrin.
31561469	0	3	theme	Pit	67:69	arg1	Viper					71:75	the Peruvian Pit Viper	54:75	the Peruvian Pit Viper Snake Bothrops atrox	54:96	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	0	4	theme	Platelet	152:159	arg1	Function					161:168	Platelet Function	152:168	Platelet Function	152:168	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	7	5	theme	Zn2+-complexing	767:781	arg1	residues					793:800	the Zn2+-complexing histidine residues	763:800	the Zn2+-complexing histidine residues within the active site	763:823	Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it.
31561469	1	6	theme	Bothrops	227:234	arg1	atrox					236:240	Bothrops atrox	227:240	Bothrops atrox	227:240	Atroxlysin-III (Atr-III) was purified from the venom of Bothrops atrox.
31561469	0	7	theme	Bothrops	83:90	arg1	atrox					92:96	the Peruvian Pit Viper Snake Bothrops atrox	54:96	the Peruvian Pit Viper Snake Bothrops atrox	54:96	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	14	8	theme	envenomation	1574:1585	arg1	effect					1564:1569	the antithrombotic effect	1545:1569	the antithrombotic effect of envenomation by Bothrops atrox	1545:1603	Selectively, Atr-III targets GPVI antagonistically and thus contributes to the antithrombotic effect of envenomation by Bothrops atrox.
31561469	8	9	theme	fibrinogen	959:968	arg1	α-chains					947:954	the α-chains	943:954	the α-chains of fibrinogen and fibrin	943:979	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	8	9	theme	fibrinogen	959:968	arg1	fibronectin					902:912	plasma fibronectin	895:912	plasma fibronectin	895:912	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	8	9	theme	fibrinogen	959:968	arg1	I-collagen					920:929	type I-collagen	915:929	type I-collagen	915:929	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	12	10	theme	soluble	1334:1340	arg1	sGPVI					1360:1364	sGPVI	1360:1364	sGPVI	1360:1364	In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI).
31561469	12	10	theme	soluble	1334:1340	arg1	fragment					1350:1357	a soluble ~55-kDa fragment	1332:1357	a soluble ~55-kDa fragment (sGPVI)	1332:1365	In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI).
31561469	1	11	theme	atrox	236:240	arg1	venom					218:222	the venom	214:222	the venom of Bothrops atrox	214:240	Atroxlysin-III (Atr-III) was purified from the venom of Bothrops atrox.
31561469	3	12	theme	amino	357:361	arg1	sequence					368:375	Its cDNA-deduced amino acid sequence	340:375	Its cDNA-deduced amino acid sequence	340:375	Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain.
31561469	9	13	theme	binding	1043:1049	arg1	site					1051:1054	the binding site	1039:1054	the binding site for GPIb	1039:1063	The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed.
31561469	0	14	from	Venom	45:49	arg1	Atroxlysin-III					0:13	Atroxlysin-III	0:13	Atroxlysin-III	0:13	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	0	14	from	Venom	45:49	arg1	Metalloproteinase					18:34	A Metalloproteinase	16:34	A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox	16:96	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	5	15	theme	enzymatic	603:611	arg1	activity					613:620	Its enzymatic activity	599:620	Its enzymatic activity	599:620	Its enzymatic activity is metal ion-dependent.
31561469	2	16	theme	56-kDa	248:253	arg1	protein					255:261	This 56-kDa protein	243:261	This 56-kDa protein	243:261	This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase.
31561469	0	17	theme	atrox	92:96	arg1	Venom					45:49	the Venom	41:49	the Venom of the Peruvian Pit Viper Snake Bothrops atrox	41:96	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	14	18	theme	antithrombotic	1549:1562	arg1	effect					1564:1569	the antithrombotic effect	1545:1569	the antithrombotic effect of envenomation by Bothrops atrox	1545:1603	Selectively, Atr-III targets GPVI antagonistically and thus contributes to the antithrombotic effect of envenomation by Bothrops atrox.
31561469	7	19	theme	Chemical	738:745	arg1	modification					747:758	Chemical modification	738:758	Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC)	738:860	Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it.
31561469	7	20	theme	residues	793:800	arg1	modification					747:758	Chemical modification	738:758	Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC)	738:860	Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it.
31561469	5	21	theme	metal	625:629	arg1	ion-dependent					631:643	metal ion-dependent	625:643	metal ion-dependent	625:643	Its enzymatic activity is metal ion-dependent.
31561469	8	22	theme	plasma	895:900	arg1	fibronectin					902:912	plasma fibronectin	895:912	plasma fibronectin	895:912	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	3	23	theme	acid	363:366	arg1	sequence					368:375	Its cDNA-deduced amino acid sequence	340:375	Its cDNA-deduced amino acid sequence	340:375	Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain.
31561469	3	24	theme	cDNA-deduced	344:355	arg1	sequence					368:375	Its cDNA-deduced amino acid sequence	340:375	Its cDNA-deduced amino acid sequence	340:375	Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain.
31561469	8	25	theme	fibrin	974:979	arg1	α-chains					947:954	the α-chains	943:954	the α-chains of fibrinogen and fibrin	943:979	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	8	25	theme	fibrin	974:979	arg1	fibronectin					902:912	plasma fibronectin	895:912	plasma fibronectin	895:912	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	8	25	theme	fibrin	974:979	arg1	I-collagen					920:929	type I-collagen	915:929	type I-collagen	915:929	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	4	26	from	jararaca	560:567	arg1	identity					505:512	Its identity	501:512	Its identity with bothropasin and jararhagin from Bothrops jararaca	501:567	Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively.
31561469	7	27	theme	histidine	783:791	arg1	residues					793:800	the Zn2+-complexing histidine residues	763:800	the Zn2+-complexing histidine residues within the active site	763:823	Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it.
31561469	10	28	dep	GPVI	1163:1166	arg1	VI					1159:1160	VI	1159:1160	VI	1159:1160	Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and α2β1 integrin.
31561469	2	29	theme	N-linked	269:276	arg1	glycoconjugates					278:292	N-linked glycoconjugates	269:292	N-linked glycoconjugates	269:292	This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase.
31561469	7	30	theme	active	813:818	arg1	site					820:823	the active site	809:823	the active site	809:823	Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it.
31561469	12	31	dep	glycoprotein	1304:1315	arg1	VI					1317:1318	VI	1317:1318	VI	1317:1318	In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI).
31561469	2	32	contain	bears	263:267	arg1	protein					255:261	This 56-kDa protein	243:261	This 56-kDa protein	243:261	This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase.
31561469	2	32	contain	bears	263:267	arg2	glycoconjugates					278:292	N-linked glycoconjugates	269:292	N-linked glycoconjugates	269:292	This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase.
31561469	0	33	theme	Glycoprotein	115:126	arg1	Shedding					131:138	Glycoprotein VI Shedding	115:138	Glycoprotein VI Shedding	115:138	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	13	34	theme	platelets	1404:1412	arg1	aggregation					1389:1399	aggregation	1389:1399	aggregation of platelets which had been stimulated by convulxin, a GPVI agonist	1389:1467	Thereby, it inhibits aggregation of platelets which had been stimulated by convulxin, a GPVI agonist.
31561469	9	35	theme	von	986:988	arg1	vWF					1009:1011	vWF	1009:1011	vWF	1009:1011	The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed.
31561469	9	35	theme	von	986:988	arg1	factor					1001:1006	von Willebrand factor	986:1006	The von Willebrand factor (vWF) A1-domain	982:1022	The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed.
31561469	3	36	theme	multidomain	387:397	arg1	structure					399:407	a multidomain structure	385:407	a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain	385:498	Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain.
31561469	2	37	link	N-linked	269:276	arg1	glycoconjugates					278:292	N-linked glycoconjugates	269:292	N-linked glycoconjugates	269:292	This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase.
31561469	11	38	theme	α2β1	1201:1204	arg1	fragmented					1252:1261	fragmented	1252:1261	fragmented	1252:1261	Neither the α2β1 integrin nor its collagen-binding A-domain is fragmented by Atr-III.
31561469	11	38	theme	α2β1	1201:1204	arg1	integrin					1206:1213	the α2β1 integrin	1197:1213	the α2β1 integrin	1197:1213	Neither the α2β1 integrin nor its collagen-binding A-domain is fragmented by Atr-III.
31561469	8	39	theme	type	915:918	arg1	I-collagen					920:929	type I-collagen	915:929	type I-collagen	915:929	Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-chains of fibrinogen and fibrin.
31561469	9	40	theme	factor	1001:1006	arg1	A1-domain					1014:1022	The von Willebrand factor (vWF) A1-domain	982:1022	The von Willebrand factor (vWF) A1-domain	982:1022	The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed.
31561469	4	41	theme	Bothrops	551:558	arg1	jararaca					560:567	Bothrops jararaca	551:567	Bothrops jararaca	551:567	Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively.
31561469	2	42	theme	hemorrhagic	309:319	arg1	metalloproteinase					321:337	a P-III hemorrhagic metalloproteinase	301:337	a P-III hemorrhagic metalloproteinase	301:337	This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase.
31561469	10	43	gly	glycoprotein	1146:1157	arg1	glycoprotein					1146:1157	glycoprotein VI (GPVI)	1146:1167	glycoprotein VI (GPVI)	1146:1167	Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and α2β1 integrin.
31561469	2	44	theme	P-III	303:307	arg1	metalloproteinase					321:337	a P-III hemorrhagic metalloproteinase	301:337	a P-III hemorrhagic metalloproteinase	301:337	This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase.
31561469	6	45	theme	divalent	650:657	arg1	Ca2+					677:680	Ca2+	677:680	Ca2+	677:680	The divalent cations, Mg2+ and Ca2+, enhance its activity, whereas excess Zn2+ inhibits it.
31561469	6	45	theme	divalent	650:657	arg1	Mg2+					668:671	Mg2+	668:671	Mg2+	668:671	The divalent cations, Mg2+ and Ca2+, enhance its activity, whereas excess Zn2+ inhibits it.
31561469	6	45	theme	divalent	650:657	arg1	cations					659:665	The divalent cations	646:665	The divalent cations	646:665	The divalent cations, Mg2+ and Ca2+, enhance its activity, whereas excess Zn2+ inhibits it.
31561469	12	46	theme	~55-kDa	1342:1348	arg1	sGPVI					1360:1364	sGPVI	1360:1364	sGPVI	1360:1364	In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI).
31561469	12	46	theme	~55-kDa	1342:1348	arg1	fragment					1350:1357	a soluble ~55-kDa fragment	1332:1357	a soluble ~55-kDa fragment (sGPVI)	1332:1365	In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI).
31561469	4	47	with	identity	505:512	arg1	jararhagin					535:544	jararhagin	535:544	jararhagin	535:544	Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively.
31561469	4	47	with	identity	505:512	arg1	bothropasin					519:529	bothropasin	519:529	bothropasin	519:529	Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively.
31561469	3	48	theme	cysteine-rich	479:491	arg1	domain					493:498	a cysteine-rich domain	477:498	a cysteine-rich domain	477:498	Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain.
31561469	10	49	theme	α2β1	1174:1177	arg1	integrin					1179:1186	α2β1 integrin	1174:1186	α2β1 integrin	1174:1186	Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and α2β1 integrin.
31561469	0	50	dep	Shedding	131:138	arg1	VI					128:129	VI	128:129	VI	128:129	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	0	51	theme	Peruvian	58:65	arg1	Viper					71:75	the Peruvian Pit Viper	54:75	the Peruvian Pit Viper Snake Bothrops atrox	54:96	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31561469	6	52	theme	excess	713:718	arg1	Zn2+					720:723	excess Zn2+	713:723	excess Zn2+	713:723	The divalent cations, Mg2+ and Ca2+, enhance its activity, whereas excess Zn2+ inhibits it.
31561469	11	53	theme	collagen-binding	1223:1238	arg1	A-domain					1240:1247	its collagen-binding A-domain	1219:1247	its collagen-binding A-domain	1219:1247	Neither the α2β1 integrin nor its collagen-binding A-domain is fragmented by Atr-III.
31561469	12	54	gly	glycoprotein	1304:1315	arg1	glycoprotein					1304:1315	glycoprotein VI (GPVI)	1304:1325	glycoprotein VI (GPVI)	1304:1325	In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI).
31561469	9	55	theme	Willebrand	990:999	arg1	vWF					1009:1011	vWF	1009:1011	vWF	1009:1011	The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed.
31561469	9	55	theme	Willebrand	990:999	arg1	factor					1001:1006	von Willebrand factor	986:1006	The von Willebrand factor (vWF) A1-domain	982:1022	The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed.
31561469	13	56	theme	GPVI	1456:1459	arg1	convulxin					1443:1451	convulxin	1443:1451	convulxin	1443:1451	Thereby, it inhibits aggregation of platelets which had been stimulated by convulxin, a GPVI agonist.
31561469	13	56	theme	GPVI	1456:1459	arg1	agonist					1461:1467	a GPVI agonist	1454:1467	a GPVI agonist	1454:1467	Thereby, it inhibits aggregation of platelets which had been stimulated by convulxin, a GPVI agonist.
31561469	0	57	theme	Snake	77:81	arg1	atrox					92:96	the Peruvian Pit Viper Snake Bothrops atrox	54:96	the Peruvian Pit Viper Snake Bothrops atrox	54:96	Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.
31327656	3	0	theme	enzymatic	525:533	arg1	digestion					535:543	enzymatic digestion	525:543	enzymatic digestion	525:543	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	3	0	theme	enzymatic	525:533	arg1	process					548:554	a process	546:554	a process termed sample deglycosylation	546:584	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	5	1	theme	antigen	808:814	arg1	retrieval					816:824	PD-L1 antigen retrieval	802:824	PD-L1 antigen retrieval	802:824	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	0	2	theme	Therapeutic	88:98	arg1	Efficacy					100:107	Anti-PD-1/PD-L1 Therapeutic Efficacy	72:107	Anti-PD-1/PD-L1 Therapeutic Efficacy	72:107	Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy.
31327656	3	3	theme	sample	563:568	arg1	deglycosylation					570:584	sample deglycosylation	563:584	sample deglycosylation	563:584	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	4	4	theme	antibody	646:653	arg1	affinity					663:670	anti-PD-L1 antibody binding affinity	635:670	anti-PD-L1 antibody binding affinity	635:670	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	4	5	theme	clinical	760:767	arg1	outcome					769:775	clinical outcome	760:775	clinical outcome	760:775	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	3	6	theme	surface	504:510	arg1	antigens					512:519	cell surface antigens	499:519	cell surface antigens	499:519	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	5	7	theme	PD-L1	802:806	arg1	retrieval					816:824	PD-L1 antigen retrieval	802:824	PD-L1 antigen retrieval	802:824	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	2	8	theme	patient	309:315	arg1	response					317:324	patient response	309:324	patient response	309:324	However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients.
31327656	4	9	theme	accurate	712:719	arg1	quantification					727:740	more accurate PD-L1 quantification	707:740	more accurate PD-L1 quantification	707:740	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	4	10	theme	anti-PD-L1	635:644	arg1	affinity					663:670	anti-PD-L1 antibody binding affinity	635:670	anti-PD-L1 antibody binding affinity	635:670	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	5	11	theme	practical	840:848	arg1	approach					861:868	a practical and timely approach	838:868	a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy	838:952	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	4	12	theme	binding	655:661	arg1	affinity					663:670	anti-PD-L1 antibody binding affinity	635:670	anti-PD-L1 antibody binding affinity	635:670	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	3	13	gly	glycosylated	410:421	arg1	PD-L1					393:397	PD-L1	393:397	PD-L1	393:397	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	5	14	theme	retrieval	816:824	arg1	method					792:797	This proposed method	778:797	This proposed method of PD-L1 antigen retrieval	778:824	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	2	15	theme	clinical	344:351	arg1	challenge					353:361	a clinical challenge	342:361	a clinical challenge to stratify patients	342:382	However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients.
31327656	3	16	from	antigens	512:519	arg1	moieties					485:492	the glycan moieties	474:492	the glycan moieties from cell surface antigens	474:519	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	4	17	theme	PD-L1	721:725	arg1	quantification					727:740	more accurate PD-L1 quantification	707:740	more accurate PD-L1 quantification	707:740	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	0	18	theme	Glycosylation	20:32	arg1	Removal					0:6	Removal	0:6	Removal of N-Linked Glycosylation	0:32	Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy.
31327656	1	19	theme	promising	206:214	arg1	Reactivation					110:121	Reactivation	110:121	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade	110:181	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	1	19	theme	promising	206:214	arg1	strategy					235:242	a promising cancer therapeutic strategy	204:242	a promising cancer therapeutic strategy	204:242	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	0	20	theme	N-Linked	11:18	arg1	Glycosylation					20:32	N-Linked Glycosylation	11:32	N-Linked Glycosylation	11:32	Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy.
31327656	1	21	theme	T cell	126:131	arg1	immunity					133:140	T cell immunity	126:140	T cell immunity	126:140	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	1	22	theme	cancer	216:221	arg1	Reactivation					110:121	Reactivation	110:121	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade	110:181	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	1	22	theme	cancer	216:221	arg1	strategy					235:242	a promising cancer therapeutic strategy	204:242	a promising cancer therapeutic strategy	204:242	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	0	23	theme	PD-L1	43:47	arg1	Detection					49:57	PD-L1 Detection	43:57	PD-L1 Detection	43:57	Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy.
31327656	2	24	theme	PD-L1	254:258	arg1	readout					280:286	PD-L1 immunohistochemical readout	254:286	PD-L1 immunohistochemical readout	254:286	However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients.
31327656	1	25	theme	therapeutic	223:233	arg1	Reactivation					110:121	Reactivation	110:121	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade	110:181	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	1	25	theme	therapeutic	223:233	arg1	strategy					235:242	a promising cancer therapeutic strategy	204:242	a promising cancer therapeutic strategy	204:242	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	5	26	theme	proposed	783:790	arg1	method					792:797	This proposed method	778:797	This proposed method of PD-L1 antigen retrieval	778:824	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	5	27	theme	false-negative	880:893	arg1	stratification					903:916	false-negative patient stratification	880:916	false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy	880:952	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	3	28	theme	glycan	478:483	arg1	moieties					485:492	the glycan moieties	474:492	the glycan moieties from cell surface antigens	474:519	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	5	29	theme	timely	854:859	arg1	approach					861:868	a practical and timely approach	838:868	a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy	838:952	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	1	30	theme	immunity	133:140	arg1	Reactivation					110:121	Reactivation	110:121	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade	110:181	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	1	30	theme	immunity	133:140	arg1	strategy					235:242	a promising cancer therapeutic strategy	204:242	a promising cancer therapeutic strategy	204:242	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	2	31	with	inconsistent	291:302	arg1	response					317:324	patient response	309:324	patient response	309:324	However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients.
31327656	4	32	theme	outcome	769:775	arg1	prediction					746:755	prediction	746:755	prediction of clinical outcome	746:775	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	4	32	theme	outcome	769:775	arg1	quantification					727:740	more accurate PD-L1 quantification	707:740	more accurate PD-L1 quantification	707:740	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	1	33	theme	PD-1/PD-L1	145:154	arg1	blockade					174:181	PD-1/PD-L1 immune checkpoint blockade	145:181	PD-1/PD-L1 immune checkpoint blockade	145:181	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	5	34	theme	patient	895:901	arg1	stratification					903:916	false-negative patient stratification	880:916	false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy	880:952	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	1	35	theme	immune	156:161	arg1	blockade					174:181	PD-1/PD-L1 immune checkpoint blockade	145:181	PD-1/PD-L1 immune checkpoint blockade	145:181	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	3	36	theme	cell	499:502	arg1	antigens					512:519	cell surface antigens	499:519	cell surface antigens	499:519	Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation.
31327656	0	37	theme	Anti-PD-1/PD-L1	72:86	arg1	Efficacy					100:107	Anti-PD-1/PD-L1 Therapeutic Efficacy	72:107	Anti-PD-1/PD-L1 Therapeutic Efficacy	72:107	Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy.
31327656	5	38	theme	anti-PD-1/PD-L1	930:944	arg1	therapy					946:952	anti-PD-1/PD-L1 therapy	930:952	anti-PD-1/PD-L1 therapy	930:952	This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.
31327656	1	39	theme	checkpoint	163:172	arg1	blockade					174:181	PD-1/PD-L1 immune checkpoint blockade	145:181	PD-1/PD-L1 immune checkpoint blockade	145:181	Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy.
31327656	4	40	theme	signal	676:681	arg1	intensity					683:691	signal intensity	676:691	signal intensity	676:691	Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome.
31327656	2	41	theme	immunohistochemical	260:278	arg1	readout					280:286	PD-L1 immunohistochemical readout	254:286	PD-L1 immunohistochemical readout	254:286	However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients.
30320380	7	0	theme	R‑like	1394:1399	arg1	PERK					1412:1415	PERK	1412:1415	PERK	1412:1415	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	0	theme	R‑like	1394:1399	arg1	kinase					1404:1409	protein kinase R‑like ER kinase	1379:1409	protein kinase R‑like ER kinase (PERK)	1379:1416	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	0	theme	R‑like	1394:1399	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	14	1	theme	Ca	2765:2766	arg1	homeostasis					2768:2778	ER Ca homeostasis	2762:2778	ER Ca homeostasis	2762:2778	In addition, IFNγ‑induced DSPP and MMP20 downregulation may correspond with alteration in ER Ca homeostasis.
30320380	7	2	theme	protein	1379:1385	arg1	PERK					1412:1415	PERK	1412:1415	PERK	1412:1415	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	2	theme	protein	1379:1385	arg1	kinase					1404:1409	protein kinase R‑like ER kinase	1379:1409	protein kinase R‑like ER kinase (PERK)	1379:1416	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	2	theme	protein	1379:1385	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	3	theme	inositol	1333:1340	arg1	IP3r					1372:1375	IP3r	1372:1375	IP3r	1372:1375	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	3	theme	inositol	1333:1340	arg1	receptor					1362:1369	inositol 1,4,5‑trisphosphate receptor	1333:1369	inositol 1,4,5‑trisphosphate receptor (IP3r)	1333:1376	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	3	theme	inositol	1333:1340	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	10	4	theme	GRP78	1984:1988	arg1	levels					1944:1949	the mRNA expression levels	1924:1949	the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1	1924:2046	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	8	5	theme	protein	1542:1548	arg1	levels					1561:1566	The protein expression levels	1538:1566	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c	1538:1689	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	3	6	theme	cell	708:711	arg1	OSCC					724:727	OSCC	724:727	OSCC	724:727	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	6	theme	cell	708:711	arg1	carcinoma					713:721	oral squamous cell carcinoma	694:721	oral squamous cell carcinoma (OSCC)	694:728	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	13	7	theme	PCNA	2431:2434	arg1	expression					2444:2453	PCNA protein expression	2431:2453	PCNA protein expression	2431:2453	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	1	8	theme	host	288:291	arg1	response					300:307	the host immune response	284:307	the host immune response to tumor development	284:328	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	4	9	theme	MMP	811:813	arg1	partner					815:821	the cognate MMP partner	799:821	the cognate MMP partner of DSPP	799:829	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	4	9	theme	MMP	811:813	arg1	metalloproteinase					770:786	matrix metalloproteinase (MMP)20	763:794	matrix metalloproteinase (MMP)20	763:794	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	9	10	theme	MTT	1784:1786	arg1	assays					1859:1864	MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays	1784:1864	MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays	1784:1864	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	3	11	theme	oral	694:697	arg1	OSCC					724:727	OSCC	724:727	OSCC	724:727	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	11	theme	oral	694:697	arg1	carcinoma					713:721	oral squamous cell carcinoma	694:721	oral squamous cell carcinoma (OSCC)	694:728	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	12	theme	Dentin	516:521	arg1	sialophosphoprotein					523:541	Dentin sialophosphoprotein	516:541	Dentin sialophosphoprotein (DSPP)	516:548	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	12	theme	Dentin	516:521	arg1	member					562:567	a member	560:567	a member of the small integrin‑binding N‑linked glycoproteins family	560:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	12	theme	Dentin	516:521	arg1	DSPP					544:547	DSPP	544:547	DSPP	544:547	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	8	13	theme	X	1615:1615	arg1	Bax					1626:1628	Bax	1626:1628	Bax	1626:1628	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	8	13	theme	X	1615:1615	arg1	protein					1617:1623	Bcl‑2‑associated X protein	1598:1623	Bcl‑2‑associated X protein (Bax)	1598:1629	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	14	14	theme	MMP20	2707:2711	arg1	downregulation					2713:2726	MMP20 downregulation	2707:2726	MMP20 downregulation	2707:2726	In addition, IFNγ‑induced DSPP and MMP20 downregulation may correspond with alteration in ER Ca homeostasis.
30320380	9	15	theme	Annexin	1789:1795	arg1	cytometry					1831:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	1	16	theme	proinflammatory	193:207	arg1	cytokines					209:217	proinflammatory cytokines	193:217	proinflammatory cytokines	193:217	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	7	17	theme	reticulum	1300:1308	arg1	SERCA2b					1323:1329	SERCA2b	1323:1329	SERCA2b	1323:1329	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	17	theme	reticulum	1300:1308	arg1	Ca2+‑ATPase					1310:1320	sarco/endoplasmic reticulum Ca2+‑ATPase	1282:1320	sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b)	1282:1330	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	17	theme	reticulum	1300:1308	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	9	18	theme	isothiocyanate	1811:1824	arg1	cytometry					1831:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	13	19	theme	OSCC	2559:2562	arg1	viability					2569:2577	IFNγ inhibited OSCC cell viability	2544:2577	IFNγ inhibited OSCC cell viability	2544:2577	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	9	20	theme	cytometry	1831:1839	arg1	assays					1859:1864	MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays	1784:1864	MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays	1784:1864	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	10	21	contain	had	2063:2065	arg2	effect					2082:2087	no significant effect	2067:2087	no significant effect	2067:2087	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	10	21	contain	had	2063:2065	arg1	IFNγ					2058:2061	IFNγ	2058:2061	IFNγ	2058:2061	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	5	22	theme	regulatory	996:1005	arg1	mechanisms					1007:1016	regulatory mechanisms	996:1016	regulatory mechanisms	996:1016	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	8	23	theme	proliferating	1632:1644	arg1	PCNA					1668:1671	PCNA	1668:1671	PCNA	1668:1671	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	8	23	theme	proliferating	1632:1644	arg1	antigen					1659:1665	proliferating cell nuclear antigen	1632:1665	proliferating cell nuclear antigen (PCNA)	1632:1672	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	1	24	theme	malignant	230:238	arg1	neoplasms					240:248	various malignant neoplasms	222:248	various malignant neoplasms	222:248	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	7	25	theme	chain	1522:1526	arg1	reaction					1528:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	9	26	theme	wound‑healing	1845:1857	arg1	assays					1859:1864	MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays	1784:1864	MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays	1784:1864	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	0	27	theme	endoplasmic	143:153	arg1	reticulum					155:163	the endoplasmic reticulum	139:163	the endoplasmic reticulum response	139:172	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	14	28	from	alteration	2748:2757	arg1	homeostasis					2768:2778	ER Ca homeostasis	2762:2778	ER Ca homeostasis	2762:2778	In addition, IFNγ‑induced DSPP and MMP20 downregulation may correspond with alteration in ER Ca homeostasis.
30320380	8	29	theme	nuclear	1651:1657	arg1	PCNA					1668:1671	PCNA	1668:1671	PCNA	1668:1671	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	8	29	theme	nuclear	1651:1657	arg1	antigen					1659:1665	proliferating cell nuclear antigen	1632:1665	proliferating cell nuclear antigen (PCNA)	1632:1672	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	5	30	theme	IFNγ	874:877	arg1	treatment					879:887	IFNγ treatment	874:887	IFNγ treatment	874:887	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	7	31	theme	transcription‑quantitative	1484:1509	arg1	reaction					1528:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	10	32	theme	mRNA	1928:1931	arg1	levels					1944:1949	the mRNA expression levels	1924:1949	the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1	1924:2046	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	0	33	theme	response	165:172	arg1	modulation					125:134	modulation	125:134	modulation of the endoplasmic reticulum response	125:172	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	3	34	theme	N‑linked	599:606	arg1	family					622:627	the small integrin‑binding N‑linked glycoproteins family	572:627	the small integrin‑binding N‑linked glycoproteins family	572:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	7	35	theme	[78‑kDa	1239:1245	arg1	protein					1265:1271	[78‑kDa glucose‑regulated protein	1239:1271	[78‑kDa glucose‑regulated protein (GRP78)	1239:1279	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	35	theme	[78‑kDa	1239:1245	arg1	IRE1					1451:1454	IRE1	1451:1454	IRE1	1451:1454	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	35	theme	[78‑kDa	1239:1245	arg1	GRP78					1274:1278	GRP78	1274:1278	GRP78	1274:1278	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	35	theme	[78‑kDa	1239:1245	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	10	36	theme	significant	2070:2080	arg1	effect					2082:2087	no significant effect	2067:2087	no significant effect	2067:2087	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	7	37	theme	expression	1133:1142	arg1	levels					1144:1149	the mRNA expression levels	1124:1149	the mRNA expression levels of DSPP and MMP20	1124:1167	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	3	38	theme	small	576:580	arg1	family					622:627	the small integrin‑binding N‑linked glycoproteins family	572:627	the small integrin‑binding N‑linked glycoproteins family	572:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	2	39	from	association	411:421	arg1	neck					373:376	neck	373:376	neck	373:376	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	2	39	from	association	411:421	arg1	head					364:367	head	364:367	head	364:367	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	5	40	dep	DSPP	892:895	arg1	mechanisms					1007:1016	regulatory mechanisms	996:1016	regulatory mechanisms	996:1016	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	8	41	theme	cytochrome c	1678:1689	arg1	levels					1561:1566	The protein expression levels	1538:1566	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c	1538:1689	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	2	42	from	role	335:338	arg1	neck					373:376	neck	373:376	neck	373:376	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	2	42	from	role	335:338	arg1	head					364:367	head	364:367	head	364:367	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	2	43	theme	investigation	501:513	arg1	subject					482:488	a subject	480:488	a subject of ongoing investigation	480:513	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	10	44	theme	UPR‑associated	2019:2032	arg1	IRE1					2043:2046	the UPR‑associated molecule IRE1	2015:2046	the UPR‑associated molecule IRE1	2015:2046	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	6	45	theme	specific	1082:1089	arg1	time‑points					1091:1101	specific time‑points	1082:1101	specific time‑points	1082:1101	The OSC2 OSCC cell line was treated with IFNγ at specific time‑points.
30320380	5	46	theme	ER	919:920	arg1	stress					922:927	ER stress	919:927	ER stress	919:927	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	2	47	dep	head	364:367	arg1	carcinoma					392:400	squamous cell carcinoma	378:400	squamous cell carcinoma	378:400	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	2	48	theme	cell	387:390	arg1	carcinoma					392:400	squamous cell carcinoma	378:400	squamous cell carcinoma	378:400	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	8	49	theme	western	1708:1714	arg1	blotting					1716:1723	western blotting	1708:1723	western blotting	1708:1723	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	2	50	theme	reticulum 	440:449	arg1	pathways					462:469	endoplasmic reticulum (ER) stress pathways	428:469	endoplasmic reticulum (ER) stress pathways	428:469	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	0	51	from	sialophosphoprotein	31:49	arg1	cells					83:87	oral squamous cell carcinoma cells	54:87	oral squamous cell carcinoma cells resulting in antitumor effects	54:118	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	0	52	theme	carcinoma	73:81	arg1	cells					83:87	oral squamous cell carcinoma cells	54:87	oral squamous cell carcinoma cells resulting in antitumor effects	54:118	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	11	53	theme	ER	2114:2115	arg1	homeostasis					2120:2130	ER Ca homeostasis	2114:2130	ER Ca homeostasis molecules	2114:2140	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	0	54	theme	Interferon	0:9	arg1	γ					11:11	Interferon γ	0:11	Interferon γ	0:11	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	1	55	theme	immune	293:298	arg1	response					300:307	the host immune response	284:307	the host immune response to tumor development	284:328	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	13	56	theme	UPR	2656:2658	arg1	mechanisms					2660:2669	ER stress and UPR mechanisms	2642:2669	ER stress and UPR mechanisms	2642:2669	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	7	57	theme	Ca	1204:1205	arg1	receptor					1362:1369	inositol 1,4,5‑trisphosphate receptor	1333:1369	inositol 1,4,5‑trisphosphate receptor (IP3r)	1333:1376	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	57	theme	Ca	1204:1205	arg1	enzyme 1					1441:1448	inositol‑requiring enzyme 1	1422:1448	inositol‑requiring enzyme 1	1422:1448	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	57	theme	Ca	1204:1205	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	57	theme	Ca	1204:1205	arg1	kinase					1404:1409	protein kinase R‑like ER kinase	1379:1409	protein kinase R‑like ER kinase (PERK)	1379:1416	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	57	theme	Ca	1204:1205	arg1	protein					1265:1271	[78‑kDa glucose‑regulated protein	1239:1271	[78‑kDa glucose‑regulated protein (GRP78)	1239:1279	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	57	theme	Ca	1204:1205	arg1	Ca2+‑ATPase					1310:1320	sarco/endoplasmic reticulum Ca2+‑ATPase	1282:1320	sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b)	1282:1330	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	58	theme	inositol‑requiring	1422:1439	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	58	theme	inositol‑requiring	1422:1439	arg1	enzyme 1					1441:1448	inositol‑requiring enzyme 1	1422:1448	inositol‑requiring enzyme 1	1422:1448	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	2	59	theme	stress	455:460	arg1	pathways					462:469	endoplasmic reticulum (ER) stress pathways	428:469	endoplasmic reticulum (ER) stress pathways	428:469	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	0	60	theme	cell	68:71	arg1	carcinoma					73:81	oral squamous cell carcinoma	54:81	oral squamous cell carcinoma cells resulting in antitumor effects	54:118	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	13	61	with	treatment	2359:2367	arg1	IFNγ					2374:2377	IFNγ	2374:2377	IFNγ	2374:2377	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	2	62	theme	ER	451:452	arg1	pathways					462:469	endoplasmic reticulum (ER) stress pathways	428:469	endoplasmic reticulum (ER) stress pathways	428:469	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	12	63	theme	mRNA	2274:2277	arg1	levels					2290:2295	DSPP and MMP20 mRNA expression levels	2259:2295	DSPP and MMP20 mRNA expression levels	2259:2295	Furthermore, DSPP and MMP20 mRNA expression levels were significantly reduced following IFNγ treatment.
30320380	3	64	theme	family	622:627	arg1	member					562:567	a member	560:567	a member of the small integrin‑binding N‑linked glycoproteins family	560:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	64	theme	family	622:627	arg1	sialophosphoprotein					523:541	Dentin sialophosphoprotein	516:541	Dentin sialophosphoprotein (DSPP)	516:548	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	11	65	dep	molecules	2132:2140	arg1	regards					2103:2109	regards	2103:2109	regards	2103:2109	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	0	66	theme	oral	54:57	arg1	carcinoma					73:81	oral squamous cell carcinoma	54:81	oral squamous cell carcinoma cells resulting in antitumor effects	54:118	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	7	67	dep	proteins	1230:1237	arg1	receptor					1362:1369	inositol 1,4,5‑trisphosphate receptor	1333:1369	inositol 1,4,5‑trisphosphate receptor (IP3r)	1333:1376	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	SERCA2b					1323:1329	SERCA2b	1323:1329	SERCA2b	1323:1329	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	GRP78					1274:1278	GRP78	1274:1278	GRP78	1274:1278	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	enzyme 1					1441:1448	inositol‑requiring enzyme 1	1422:1448	inositol‑requiring enzyme 1	1422:1448	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	IP3r					1372:1375	IP3r	1372:1375	IP3r	1372:1375	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	kinase					1404:1409	protein kinase R‑like ER kinase	1379:1409	protein kinase R‑like ER kinase (PERK)	1379:1416	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	PERK					1412:1415	PERK	1412:1415	PERK	1412:1415	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	IRE1					1451:1454	IRE1	1451:1454	IRE1	1451:1454	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	protein					1265:1271	[78‑kDa glucose‑regulated protein	1239:1271	[78‑kDa glucose‑regulated protein (GRP78)	1239:1279	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	67	dep	proteins	1230:1237	arg1	Ca2+‑ATPase					1310:1320	sarco/endoplasmic reticulum Ca2+‑ATPase	1282:1320	sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b)	1282:1330	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	6	68	theme	OSCC	1042:1045	arg1	line					1052:1055	The OSC2 OSCC cell line	1033:1055	The OSC2 OSCC cell line	1033:1055	The OSC2 OSCC cell line was treated with IFNγ at specific time‑points.
30320380	9	69	theme	Cell	1726:1729	arg1	viability					1731:1739	Cell viability	1726:1739	Cell viability	1726:1739	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	3	70	theme	malignant	653:661	arg1	transformation					663:676	transformation	663:676	transformation	663:676	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	2	71	theme	interferon	343:352	arg1	γ					359:359	interferon (IFN)γ	343:359	interferon (IFN)γ	343:359	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	8	72	theme	expression	1550:1559	arg1	levels					1561:1566	The protein expression levels	1538:1566	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c	1538:1689	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	7	73	theme	ER	1401:1402	arg1	PERK					1412:1415	PERK	1412:1415	PERK	1412:1415	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	73	theme	ER	1401:1402	arg1	kinase					1404:1409	protein kinase R‑like ER kinase	1379:1409	protein kinase R‑like ER kinase (PERK)	1379:1416	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	73	theme	ER	1401:1402	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	5	74	theme	unfolded	934:941	arg1	UPR					961:963	UPR	961:963	UPR	961:963	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	5	74	theme	unfolded	934:941	arg1	response					951:958	the unfolded protein response	930:958	the unfolded protein response (UPR)	930:964	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	10	75	theme	ER	1964:1965	arg1	GRP78					1984:1988	the major ER stress regulator GRP78	1954:1988	the major ER stress regulator GRP78	1954:1988	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	11	76	theme	homeostasis	2120:2130	arg1	molecules					2132:2140	ER Ca homeostasis molecules	2114:2140	ER Ca homeostasis molecules	2114:2140	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	13	77	theme	ER	2642:2643	arg1	stress					2645:2650	ER stress	2642:2650	ER stress	2642:2650	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	7	78	theme	kinase	1387:1392	arg1	PERK					1412:1415	PERK	1412:1415	PERK	1412:1415	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	78	theme	kinase	1387:1392	arg1	kinase					1404:1409	protein kinase R‑like ER kinase	1379:1409	protein kinase R‑like ER kinase (PERK)	1379:1416	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	78	theme	kinase	1387:1392	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	13	79	theme	cell	2412:2415	arg1	viability					2417:2425	cell viability	2412:2425	cell viability	2412:2425	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	2	80	theme	γ	359:359	arg1	association					411:421	its association	407:421	its association with endoplasmic reticulum (ER) stress pathways	407:469	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	2	80	theme	γ	359:359	arg1	role					335:338	The role	331:338	The role of interferon (IFN)γ in head and neck squamous cell carcinoma	331:400	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	8	81	theme	lymphoma	1578:1585	arg1	levels					1561:1566	The protein expression levels	1538:1566	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c	1538:1689	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	4	82	theme	DSPP	826:829	arg1	partner					815:821	the cognate MMP partner	799:821	the cognate MMP partner of DSPP	799:829	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	4	82	theme	DSPP	826:829	arg1	metalloproteinase					770:786	matrix metalloproteinase (MMP)20	763:794	matrix metalloproteinase (MMP)20	763:794	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	11	83	theme	SERCA2b	2207:2213	arg1	levels					2197:2202	the mRNA expression levels	2177:2202	the mRNA expression levels of SERCA2b	2177:2213	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	7	84	theme	1,4,5‑trisphosphate	1342:1360	arg1	IP3r					1372:1375	IP3r	1372:1375	IP3r	1372:1375	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	84	theme	1,4,5‑trisphosphate	1342:1360	arg1	receptor					1362:1369	inositol 1,4,5‑trisphosphate receptor	1333:1369	inositol 1,4,5‑trisphosphate receptor (IP3r)	1333:1376	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	84	theme	1,4,5‑trisphosphate	1342:1360	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	3	85	gly	glycoproteins	608:620	arg1	glycoproteins					608:620	the small integrin‑binding N‑linked glycoproteins family	572:627	the small integrin‑binding N‑linked glycoproteins family	572:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	86	theme	carcinoma	713:721	arg1	invasion					682:689	invasion	682:689	invasion	682:689	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	86	theme	carcinoma	713:721	arg1	transformation					663:676	transformation	663:676	transformation	663:676	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	13	87	theme	OSC2	2388:2391	arg1	migration					2393:2401	OSC2 migration	2388:2401	OSC2 migration	2388:2401	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	4	88	theme	cognate	803:809	arg1	partner					815:821	the cognate MMP partner	799:821	the cognate MMP partner of DSPP	799:829	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	4	88	theme	cognate	803:809	arg1	metalloproteinase					770:786	matrix metalloproteinase (MMP)20	763:794	matrix metalloproteinase (MMP)20	763:794	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	10	89	theme	lesser	2000:2005	arg1	extent					2007:2012	a lesser extent	1998:2012	a lesser extent	1998:2012	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	3	90	theme	squamous	699:706	arg1	OSCC					724:727	OSCC	724:727	OSCC	724:727	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	3	90	theme	squamous	699:706	arg1	carcinoma					713:721	oral squamous cell carcinoma	694:721	oral squamous cell carcinoma (OSCC)	694:728	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	8	91	theme	Bcl‑2‑associated	1598:1613	arg1	Bax					1626:1628	Bax	1626:1628	Bax	1626:1628	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	8	91	theme	Bcl‑2‑associated	1598:1613	arg1	protein					1617:1623	Bcl‑2‑associated X protein	1598:1623	Bcl‑2‑associated X protein (Bax)	1598:1629	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	9	92	theme	V‑fluorescein	1797:1809	arg1	cytometry					1831:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	8	93	theme	protein	1617:1623	arg1	levels					1561:1566	The protein expression levels	1538:1566	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c	1538:1689	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	1	94	theme	cytokines	209:217	arg1	expression					179:188	The expression	175:188	The expression of proinflammatory cytokines in various malignant neoplasms	175:248	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	14	95	theme	IFNγ‑induced	2685:2696	arg1	DSPP					2698:2701	IFNγ‑induced DSPP	2685:2701	IFNγ‑induced DSPP	2685:2701	In addition, IFNγ‑induced DSPP and MMP20 downregulation may correspond with alteration in ER Ca homeostasis.
30320380	9	96	theme	flow	1826:1829	arg1	cytometry					1831:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Annexin V‑fluorescein isothiocyanate flow cytometry	1789:1839	Cell viability, apoptosis and migration were evaluated by MTT, Annexin V‑fluorescein isothiocyanate flow cytometry and wound‑healing assays, respectively.
30320380	14	97	theme	ER	2762:2763	arg1	homeostasis					2768:2778	ER Ca homeostasis	2762:2778	ER Ca homeostasis	2762:2778	In addition, IFNγ‑induced DSPP and MMP20 downregulation may correspond with alteration in ER Ca homeostasis.
30320380	5	98	theme	present	836:842	arg1	study					844:848	The present study	832:848	The present study	832:848	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	1	99	theme	various	222:228	arg1	neoplasms					240:248	various malignant neoplasms	222:248	various malignant neoplasms	222:248	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	10	100	theme	regulator	1974:1982	arg1	GRP78					1984:1988	the major ER stress regulator GRP78	1954:1988	the major ER stress regulator GRP78	1954:1988	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	7	101	theme	polymerase	1511:1520	arg1	reaction					1528:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	102	theme	sarco/endoplasmic	1282:1298	arg1	SERCA2b					1323:1329	SERCA2b	1323:1329	SERCA2b	1323:1329	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	102	theme	sarco/endoplasmic	1282:1298	arg1	Ca2+‑ATPase					1310:1320	sarco/endoplasmic reticulum Ca2+‑ATPase	1282:1320	sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b)	1282:1330	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	102	theme	sarco/endoplasmic	1282:1298	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	10	103	theme	IFNγ	1881:1884	arg1	treatment					1886:1894	IFNγ treatment	1881:1894	IFNγ treatment	1881:1894	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	0	104	theme	reticulum	155:163	arg1	response					165:172	the endoplasmic reticulum response	139:172	the endoplasmic reticulum response	139:172	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	2	105	with	association	411:421	arg1	pathways					462:469	endoplasmic reticulum (ER) stress pathways	428:469	endoplasmic reticulum (ER) stress pathways	428:469	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	7	106	theme	reverse	1476:1482	arg1	reaction					1528:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	reverse transcription‑quantitative polymerase chain reaction	1476:1535	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	5	107	theme	calcium	971:977	arg1	homeostasis					984:994	calcium (Ca) homeostasis	971:994	calcium (Ca) homeostasis	971:994	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	3	108	theme	integrin‑binding	582:597	arg1	family					622:627	the small integrin‑binding N‑linked glycoproteins family	572:627	the small integrin‑binding N‑linked glycoproteins family	572:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	8	109	theme	cell	1646:1649	arg1	PCNA					1668:1671	PCNA	1668:1671	PCNA	1668:1671	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	8	109	theme	cell	1646:1649	arg1	antigen					1659:1665	proliferating cell nuclear antigen	1632:1665	proliferating cell nuclear antigen (PCNA)	1632:1672	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	5	110	theme	treatment	879:887	arg1	effects					863:869	the effects	859:869	the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms	859:1016	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	10	111	theme	molecule	2034:2041	arg1	IRE1					2043:2046	the UPR‑associated molecule IRE1	2015:2046	the UPR‑associated molecule IRE1	2015:2046	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	7	112	theme	MMP20	1163:1167	arg1	levels					1144:1149	the mRNA expression levels	1124:1149	the mRNA expression levels of DSPP and MMP20	1124:1167	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	113	theme	mRNA	1128:1131	arg1	levels					1144:1149	the mRNA expression levels	1124:1149	the mRNA expression levels of DSPP and MMP20	1124:1167	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	5	114	theme	Ca	980:981	arg1	homeostasis					984:994	calcium (Ca) homeostasis	971:994	calcium (Ca) homeostasis	971:994	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	8	115	theme	antigen	1659:1665	arg1	levels					1561:1566	The protein expression levels	1538:1566	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c	1538:1689	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	7	116	theme	glucose‑regulated	1247:1263	arg1	protein					1265:1271	[78‑kDa glucose‑regulated protein	1239:1271	[78‑kDa glucose‑regulated protein (GRP78)	1239:1279	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	116	theme	glucose‑regulated	1247:1263	arg1	IRE1					1451:1454	IRE1	1451:1454	IRE1	1451:1454	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	116	theme	glucose‑regulated	1247:1263	arg1	GRP78					1274:1278	GRP78	1274:1278	GRP78	1274:1278	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	116	theme	glucose‑regulated	1247:1263	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	11	117	theme	Ca	2117:2118	arg1	homeostasis					2120:2130	ER Ca homeostasis	2114:2130	ER Ca homeostasis molecules	2114:2140	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	13	118	theme	Overall	2535:2541	arg1	cytochrome c.					2521:2533	cytochrome c. Overall	2521:2541	cytochrome c. Overall	2521:2541	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	1	119	from	expression	179:188	arg1	neoplasms					240:248	various malignant neoplasms	222:248	various malignant neoplasms	222:248	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	0	120	theme	antitumor	102:110	arg1	effects					112:118	antitumor effects	102:118	antitumor effects	102:118	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	5	121	from	effects	863:869	arg1	response					951:958	the unfolded protein response	930:958	the unfolded protein response (UPR)	930:964	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	5	121	from	effects	863:869	arg1	stress					922:927	ER stress	919:927	ER stress	919:927	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	5	121	from	effects	863:869	arg1	UPR					961:963	UPR	961:963	UPR	961:963	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	5	121	from	effects	863:869	arg1	DSPP					892:895	DSPP	892:895	DSPP	892:895	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	5	121	from	effects	863:869	arg1	homeostasis					984:994	calcium (Ca) homeostasis	971:994	calcium (Ca) homeostasis	971:994	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	5	121	from	effects	863:869	arg1	expression					907:916	MMP20 expression	901:916	MMP20 expression	901:916	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	2	122	with	role	335:338	arg1	pathways					462:469	endoplasmic reticulum (ER) stress pathways	428:469	endoplasmic reticulum (ER) stress pathways	428:469	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	2	123	theme	ongoing	493:499	arg1	investigation					501:513	ongoing investigation	493:513	ongoing investigation	493:513	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	4	124	theme	Recent	731:736	arg1	studies					738:744	Recent studies	731:744	Recent studies	731:744	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	10	125	theme	expression	1933:1942	arg1	levels					1944:1949	the mRNA expression levels	1924:1949	the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1	1924:2046	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	5	126	theme	OSCC	1021:1024	arg1	cells					1026:1030	OSCC cells	1021:1030	OSCC cells	1021:1030	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	11	127	theme	mRNA	2181:2184	arg1	levels					2197:2202	the mRNA expression levels	2177:2202	the mRNA expression levels of SERCA2b	2177:2213	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	7	128	theme	homeostasis‑associated	1207:1228	arg1	receptor					1362:1369	inositol 1,4,5‑trisphosphate receptor	1333:1369	inositol 1,4,5‑trisphosphate receptor (IP3r)	1333:1376	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	128	theme	homeostasis‑associated	1207:1228	arg1	enzyme 1					1441:1448	inositol‑requiring enzyme 1	1422:1448	inositol‑requiring enzyme 1	1422:1448	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	128	theme	homeostasis‑associated	1207:1228	arg1	proteins					1230:1237	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)]	1204:1456	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	128	theme	homeostasis‑associated	1207:1228	arg1	kinase					1404:1409	protein kinase R‑like ER kinase	1379:1409	protein kinase R‑like ER kinase (PERK)	1379:1416	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	128	theme	homeostasis‑associated	1207:1228	arg1	protein					1265:1271	[78‑kDa glucose‑regulated protein	1239:1271	[78‑kDa glucose‑regulated protein (GRP78)	1239:1279	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	7	128	theme	homeostasis‑associated	1207:1228	arg1	Ca2+‑ATPase					1310:1320	sarco/endoplasmic reticulum Ca2+‑ATPase	1282:1320	sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b)	1282:1330	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	2	129	theme	squamous	378:385	arg1	carcinoma					392:400	squamous cell carcinoma	378:400	squamous cell carcinoma	378:400	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	2	130	theme	endoplasmic	428:438	arg1	pathways					462:469	endoplasmic reticulum (ER) stress pathways	428:469	endoplasmic reticulum (ER) stress pathways	428:469	The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation.
30320380	0	131	theme	dentin	24:29	arg1	sialophosphoprotein					31:49	dentin sialophosphoprotein	24:49	dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects	24:118	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	5	132	theme	MMP20	901:905	arg1	expression					907:916	MMP20 expression	901:916	MMP20 expression	901:916	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	3	133	link	N‑linked	599:606	arg1	family					622:627	the small integrin‑binding N‑linked glycoproteins family	572:627	the small integrin‑binding N‑linked glycoproteins family	572:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	12	134	theme	IFNγ	2334:2337	arg1	treatment					2339:2347	IFNγ treatment	2334:2347	IFNγ treatment	2334:2347	Furthermore, DSPP and MMP20 mRNA expression levels were significantly reduced following IFNγ treatment.
30320380	13	135	theme	cell	2564:2567	arg1	viability					2569:2577	IFNγ inhibited OSCC cell viability	2544:2577	IFNγ inhibited OSCC cell viability	2544:2577	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	13	136	theme	protein	2436:2442	arg1	expression					2444:2453	PCNA protein expression	2431:2453	PCNA protein expression	2431:2453	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	1	137	theme	tumor	312:316	arg1	development					318:328	tumor development	312:328	tumor development	312:328	The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development.
30320380	11	138	theme	expression	2186:2195	arg1	levels					2197:2202	the mRNA expression levels	2177:2202	the mRNA expression levels of SERCA2b	2177:2213	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	12	139	theme	expression	2279:2288	arg1	levels					2290:2295	DSPP and MMP20 mRNA expression levels	2259:2295	DSPP and MMP20 mRNA expression levels	2259:2295	Furthermore, DSPP and MMP20 mRNA expression levels were significantly reduced following IFNγ treatment.
30320380	3	140	theme	glycoproteins	608:620	arg1	family					622:627	the small integrin‑binding N‑linked glycoproteins family	572:627	the small integrin‑binding N‑linked glycoproteins family	572:627	Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC).
30320380	0	141	theme	squamous	59:66	arg1	carcinoma					73:81	oral squamous cell carcinoma	54:81	oral squamous cell carcinoma cells resulting in antitumor effects	54:118	Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.
30320380	6	142	theme	cell	1047:1050	arg1	line					1052:1055	The OSC2 OSCC cell line	1033:1055	The OSC2 OSCC cell line	1033:1055	The OSC2 OSCC cell line was treated with IFNγ at specific time‑points.
30320380	13	143	theme	stress	2645:2650	arg1	mechanisms					2660:2669	ER stress and UPR mechanisms	2642:2669	ER stress and UPR mechanisms	2642:2669	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
30320380	6	144	theme	OSC2	1037:1040	arg1	line					1052:1055	The OSC2 OSCC cell line	1033:1055	The OSC2 OSCC cell line	1033:1055	The OSC2 OSCC cell line was treated with IFNγ at specific time‑points.
30320380	10	145	theme	stress	1967:1972	arg1	GRP78					1984:1988	the major ER stress regulator GRP78	1954:1988	the major ER stress regulator GRP78	1954:1988	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	12	146	theme	DSPP	2259:2262	arg1	levels					2290:2295	DSPP and MMP20 mRNA expression levels	2259:2295	DSPP and MMP20 mRNA expression levels	2259:2295	Furthermore, DSPP and MMP20 mRNA expression levels were significantly reduced following IFNγ treatment.
30320380	4	147	theme	matrix	763:768	arg1	partner					815:821	the cognate MMP partner	799:821	the cognate MMP partner of DSPP	799:829	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	4	147	theme	matrix	763:768	arg1	MMP					789:791	MMP	789:791	MMP	789:791	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	4	147	theme	matrix	763:768	arg1	metalloproteinase					770:786	matrix metalloproteinase (MMP)20	763:794	matrix metalloproteinase (MMP)20	763:794	Recent studies have established matrix metalloproteinase (MMP)20 as the cognate MMP partner of DSPP.
30320380	8	148	theme	B‑cell	1571:1576	arg1	lymphoma					1578:1585	B‑cell lymphoma 2	1571:1587	B‑cell lymphoma 2 (Bcl‑2)	1571:1595	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	8	148	theme	B‑cell	1571:1576	arg1	Bcl‑2					1590:1594	Bcl‑2	1590:1594	Bcl‑2	1590:1594	The protein expression levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), proliferating cell nuclear antigen (PCNA) and cytochrome c were analyzed by western blotting.
30320380	11	149	with	treatment	2143:2151	arg1	IFNγ					2158:2161	IFNγ	2158:2161	IFNγ	2158:2161	With regards to ER Ca homeostasis molecules, treatment with IFNγ downregulated the mRNA expression levels of SERCA2b and upregulated those of IP3r.
30320380	5	150	theme	protein	943:949	arg1	UPR					961:963	UPR	961:963	UPR	961:963	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	5	150	theme	protein	943:949	arg1	response					951:958	the unfolded protein response	930:958	the unfolded protein response (UPR)	930:964	The present study examined the effects of IFNγ treatment on DSPP and MMP20 expression, ER stress, the unfolded protein response (UPR), and calcium (Ca) homeostasis regulatory mechanisms in OSCC cells.
30320380	7	151	theme	DSPP	1154:1157	arg1	levels					1144:1149	the mRNA expression levels	1124:1149	the mRNA expression levels of DSPP and MMP20	1124:1167	At each time‑point, the mRNA expression levels of DSPP and MMP20, and those of ER‑stress‑, UPR‑ and Ca homeostasis‑associated proteins [78‑kDa glucose‑regulated protein (GRP78), sarco/endoplasmic reticulum Ca2+‑ATPase (SERCA2b), inositol 1,4,5‑trisphosphate receptor (IP3r), protein kinase R‑like ER kinase (PERK) and inositol‑requiring enzyme 1 (IRE1)], were assessed by reverse transcription‑quantitative polymerase chain reaction.
30320380	10	152	theme	major	1958:1962	arg1	GRP78					1984:1988	the major ER stress regulator GRP78	1954:1988	the major ER stress regulator GRP78	1954:1988	IFNγ treatment significantly downregulated the mRNA expression levels of the major ER stress regulator GRP78 and, to a lesser extent, the UPR‑associated molecule IRE1; however, IFNγ had no significant effect on PERK.
30320380	12	153	theme	MMP20	2268:2272	arg1	levels					2290:2295	DSPP and MMP20 mRNA expression levels	2259:2295	DSPP and MMP20 mRNA expression levels	2259:2295	Furthermore, DSPP and MMP20 mRNA expression levels were significantly reduced following IFNγ treatment.
30320380	13	154	theme	inhibited	2549:2557	arg1	viability					2569:2577	IFNγ inhibited OSCC cell viability	2544:2577	IFNγ inhibited OSCC cell viability	2544:2577	Notably, treatment with IFNγ hampered OSC2 migration, reduced cell viability and PCNA protein expression, enhanced apoptosis, downregulated Bcl‑2, and upregulated Bax and cytochrome c. Overall, IFNγ inhibited OSCC cell viability and migration, and increased apoptosis, possibly by regulating ER stress and UPR mechanisms.
29915392	11	0	theme	metastasis	2068:2077	arg1	N-glycans					2030:2038	high mannose type N-glycans	2012:2038	high mannose type N-glycans	2012:2038	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	11	0	theme	metastasis	2068:2077	arg1	O-GlcNAcylation					1995:2009	O-GlcNAcylation	1995:2009	O-GlcNAcylation	1995:2009	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	11	0	theme	metastasis	2068:2077	arg1	progression					2049:2059	the progression	2045:2059	the progression of CCA metastasis	2045:2077	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	11	1	theme	metastatic	2135:2144	arg1	CCA					2146:2148	metastatic CCA	2135:2148	metastatic CCA	2135:2148	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	5	2	theme	siOGT-treated	789:801	arg1	cells					803:807	siOGT-treated cells	789:807	siOGT-treated cells	789:807	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	5	3	theme	Chip/TOF	665:672	arg1	system					678:683	an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system	636:683	an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system	636:683	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	7	4	theme	Hex5HexNAc4Fuc1NeuAc1	1105:1125	arg1	glycans					1137:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis.
29915392	8	5	from	levels	1344:1349	arg1	CCA					1354:1356	CCA	1354:1356	CCA	1354:1356	We subsequently demonstrate that suppression of O-GlcNAcylation decreased the expression of these two N-glycans, suggesting that O-GlcNAcylation mediates their levels in CCA.
29915392	2	6	theme	poor	290:293	arg1	outcome					303:309	poor patient outcome	290:309	poor patient outcome	290:309	During metastasis, cancer cells aberrantly express several glycans that are correlated with poor patient outcome.
29915392	10	7	from	increase	1773:1780	arg1	phosphorylation					1791:1805	FOXO3 phosphorylation	1785:1805	FOXO3 phosphorylation	1785:1805	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	10	8	theme	molecular	1614:1622	arg1	mechanism					1624:1632	The molecular mechanism	1610:1632	The molecular mechanism of O-GlcNAc-mediated progression of CCA	1610:1672	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	10	9	theme	N-glycans	1912:1920	arg1	accumulation					1884:1895	the accumulation	1880:1895	the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv)	1830:1925	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	5	10	theme	MS	675:676	arg1	system					678:683	an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system	636:683	an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system	636:683	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	1	11	dep	metastasis	133:142	arg1	treatment					168:176	an effective treatment	155:176	an effective treatment	155:176	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	1	11	dep	metastasis	133:142	arg1	necessary					187:195	necessary	187:195	necessary	187:195	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	9	12	theme	metastatic	1394:1403	arg1	cells					1405:1409	highly metastatic cells	1387:1409	highly metastatic cells	1387:1409	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	4	13	theme	Global	475:480	arg1	O-GlcNAcylation					482:496	Global O-GlcNAcylation	475:496	Global O-GlcNAcylation in CCA cells	475:509	Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins.
29915392	7	14	theme	biantennary	1084:1094	arg1	glycans					1137:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis.
29915392	9	15	theme	mannose	1566:1572	arg1	N-glycans					1579:1587	high mannose type N-glycans	1561:1587	high mannose type N-glycans	1561:1587	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	1	16	theme	effective	158:166	arg1	treatment					168:176	an effective treatment	155:176	an effective treatment	155:176	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	1	16	theme	effective	158:166	arg1	necessary					187:195	necessary	187:195	necessary	187:195	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	11	17	theme	CCA	2146:2148	arg1	treatment					2122:2130	treatment	2122:2130	treatment of metastatic CCA	2122:2148	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	4	18	theme	CCA	501:503	arg1	cells					505:509	CCA cells	501:509	CCA cells	501:509	Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins.
29915392	7	19	theme	complex	1096:1102	arg1	glycans					1137:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis.
29915392	1	20	theme	leading	88:94	arg1	metastasis					133:142	metastasis	133:142	metastasis	133:142	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	1	20	theme	leading	88:94	arg1	cause					96:100	The leading cause	84:100	The leading cause of death in cancer patients	84:128	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	10	21	theme	CCA	1670:1672	arg1	progression					1655:1665	O-GlcNAc-mediated progression	1637:1665	O-GlcNAc-mediated progression of CCA	1637:1672	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	3	22	theme	cholangiocarcinoma	449:466	arg1	progression					434:444	the progression	430:444	the progression of cholangiocarcinoma (CCA)	430:472	This study was aimed toward exploring the effects of O-GlcNAcylation on membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA).
29915392	3	23	theme	membranous	384:393	arg1	N-glycans					395:403	membranous N-glycans	384:403	membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA)	384:472	This study was aimed toward exploring the effects of O-GlcNAcylation on membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA).
29915392	6	24	theme	parental	898:905	arg1	KKU-214					926:932	KKU-214	926:932	KKU-214	926:932	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	24	theme	parental	898:905	arg1	KKU-213					914:920	KKU-213	914:920	KKU-213	914:920	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	24	theme	parental	898:905	arg1	cells					907:911	the parental cells	894:911	the parental cells (KKU-213 and KKU-214)	894:933	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	4	25	from	O-GlcNAcylation	482:496	arg1	cells					505:509	CCA cells	501:509	CCA cells	501:509	Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins.
29915392	9	26	theme	N-glycans	1579:1587	arg1	association					1546:1556	the association	1542:1556	the association of high mannose type N-glycans with CCA metastasis	1542:1607	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	10	27	theme	Hex9HexNAc2	1900:1910	arg1	iv					1923:1924	iv	1923:1924	iv	1923:1924	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	10	27	theme	Hex9HexNAc2	1900:1910	arg1	N-glycans					1912:1920	Hex9HexNAc2 N-glycans	1900:1920	Hex9HexNAc2 N-glycans (iv)	1900:1925	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	8	28	theme	N-glycans	1286:1294	arg1	expression					1262:1271	the expression	1258:1271	the expression of these two N-glycans	1258:1294	We subsequently demonstrate that suppression of O-GlcNAcylation decreased the expression of these two N-glycans, suggesting that O-GlcNAcylation mediates their levels in CCA.
29915392	5	29	theme	siRNA-treated	832:844	arg1	cells					846:850	scramble siRNA-treated cells	823:850	scramble siRNA-treated cells	823:850	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	5	30	theme	HPLC-Chip/Time-of-Flight	639:662	arg1	system					678:683	an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system	636:683	an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system	636:683	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	9	31	theme	cells	1405:1409	arg1	ability					1376:1382	the ability	1372:1382	the ability of highly metastatic cells to migrate and invade	1372:1431	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	11	32	theme	novel	2093:2097	arg1	target					2111:2116	a novel therapeutic target	2091:2116	a novel therapeutic target for treatment of metastatic CCA	2091:2148	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	7	33	theme	N-linked	1128:1135	arg1	glycans					1137:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis.
29915392	3	34	theme	O-GlcNAcylation	365:379	arg1	effects					354:360	the effects	350:360	the effects of O-GlcNAcylation on membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA)	350:472	This study was aimed toward exploring the effects of O-GlcNAcylation on membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA).
29915392	6	35	theme	metastatic	974:983	arg1	KKU-214L5					1006:1014	KKU-214L5	1006:1014	KKU-214L5	1006:1014	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	35	theme	metastatic	974:983	arg1	KKU-213L5					992:1000	KKU-213L5	992:1000	KKU-213L5	992:1000	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	35	theme	metastatic	974:983	arg1	cells					985:989	the highly metastatic cells	963:989	the highly metastatic cells (KKU-213L5 and KKU-214L5)	963:1015	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	11	36	theme	type	2025:2028	arg1	N-glycans					2030:2038	high mannose type N-glycans	2012:2038	high mannose type N-glycans	2012:2038	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	10	37	theme	FOXO3	1785:1789	arg1	phosphorylation					1791:1805	FOXO3 phosphorylation	1785:1805	FOXO3 phosphorylation	1785:1805	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	1	38	theme	death	105:109	arg1	metastasis					133:142	metastasis	133:142	metastasis	133:142	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	1	38	theme	death	105:109	arg1	cause					96:100	The leading cause	84:100	The leading cause of death in cancer patients	84:128	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	11	39	theme	first	1960:1964	arg1	time					1966:1969	the first time	1956:1969	the first time	1956:1969	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	2	40	theme	patient	295:301	arg1	outcome					303:309	poor patient outcome	290:309	poor patient outcome	290:309	During metastasis, cancer cells aberrantly express several glycans that are correlated with poor patient outcome.
29915392	5	41	theme	cells	803:807	arg1	N-glycans					776:784	the membranous N-glycans	761:784	the membranous N-glycans of siOGT-treated cells	761:807	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	10	42	theme	events	1721:1726	arg1	series					1701:1706	a series	1699:1706	a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv)	1699:1925	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	7	43	theme	high	1053:1056	arg1	mannose					1058:1064	high mannose	1053:1064	high mannose (Hex9HexNAc2)	1053:1078	Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis.
29915392	7	43	theme	high	1053:1056	arg1	Hex9HexNAc2					1067:1077	Hex9HexNAc2	1067:1077	Hex9HexNAc2	1067:1077	Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis.
29915392	11	44	theme	high	2012:2015	arg1	N-glycans					2030:2038	high mannose type N-glycans	2012:2038	high mannose type N-glycans	2012:2038	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	9	45	theme	Agglutinin	1478:1487	arg1	presence					1452:1459	the presence	1448:1459	the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin	1448:1520	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	0	46	theme	cholangiocarcinoma	39:56	arg1	metastasis					25:34	metastasis	25:34	metastasis of cholangiocarcinoma	25:56	O-GlcNAcylation mediates metastasis of cholangiocarcinoma through FOXO3 and MAN1A1.
29915392	8	47	theme	O-GlcNAcylation	1232:1246	arg1	suppression					1217:1227	suppression	1217:1227	suppression of O-GlcNAcylation	1217:1246	We subsequently demonstrate that suppression of O-GlcNAcylation decreased the expression of these two N-glycans, suggesting that O-GlcNAcylation mediates their levels in CCA.
29915392	3	48	from	effects	354:360	arg1	N-glycans					395:403	membranous N-glycans	384:403	membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA)	384:472	This study was aimed toward exploring the effects of O-GlcNAcylation on membranous N-glycans that are associated with the progression of cholangiocarcinoma (CCA).
29915392	11	49	theme	therapeutic	2099:2109	arg1	target					2111:2116	a novel therapeutic target	2091:2116	a novel therapeutic target for treatment of metastatic CCA	2091:2148	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	7	50	link	N-linked	1128:1135	arg1	glycans					1137:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans	1084:1143	Together, these data revealed that high mannose (Hex9HexNAc2) and biantennary complex (Hex5HexNAc4Fuc1NeuAc1) N-linked glycans correlated positively with metastasis.
29915392	10	51	theme	O-GlcNAc-mediated	1637:1653	arg1	progression					1655:1665	O-GlcNAc-mediated progression	1637:1665	O-GlcNAc-mediated progression of CCA	1637:1672	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	4	52	theme	specific	530:537	arg1	siRNA					539:543	specific siRNA	530:543	specific siRNA	530:543	Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins.
29915392	11	53	theme	CCA	2064:2066	arg1	metastasis					2068:2077	CCA metastasis	2064:2077	CCA metastasis	2064:2077	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	6	54	theme	membranous	870:879	arg1	N-glycans					881:889	the membranous N-glycans	866:889	the membranous N-glycans of the parental cells (KKU-213 and KKU-214)	866:933	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	2	55	theme	cancer	217:222	arg1	cells					224:228	cancer cells	217:228	cancer cells	217:228	During metastasis, cancer cells aberrantly express several glycans that are correlated with poor patient outcome.
29915392	6	56	theme	cells	907:911	arg1	N-glycans					881:889	the membranous N-glycans	866:889	the membranous N-glycans of the parental cells (KKU-213 and KKU-214)	866:933	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	1	57	theme	cancer	114:119	arg1	patients					121:128	cancer patients	114:128	cancer patients	114:128	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	11	58	theme	mannose	2017:2023	arg1	N-glycans					2030:2038	high mannose type N-glycans	2012:2038	high mannose type N-glycans	2012:2038	This study demonstrates for the first time the association between O-GlcNAcylation, high mannose type N-glycans, and the progression of CCA metastasis, suggesting a novel therapeutic target for treatment of metastatic CCA.
29915392	4	59	theme	O-GlcNAc	553:560	arg1	OGT					575:577	OGT	575:577	OGT	575:577	Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins.
29915392	4	59	theme	O-GlcNAc	553:560	arg1	transferase					562:572	O-GlcNAc transferase	553:572	O-GlcNAc transferase (OGT)	553:578	Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins.
29915392	10	60	theme	expression	1854:1863	arg1	reduction					1834:1842	the reduction	1830:1842	the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv)	1830:1925	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	10	60	theme	expression	1854:1863	arg1	iii					1866:1868	iii	1866:1868	iii	1866:1868	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	9	61	dep	Pisum	1464:1468	arg1	Sativum					1470:1476	Sativum	1470:1476	Sativum	1470:1476	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	9	62	with	association	1546:1556	arg1	metastasis					1598:1607	CCA metastasis	1594:1607	CCA metastasis	1594:1607	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	9	63	theme	mannose-specific	1498:1513	arg1	lectin					1515:1520	a mannose-specific lectin	1496:1520	a mannose-specific lectin	1496:1520	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	9	63	theme	mannose-specific	1498:1513	arg1	Agglutinin					1478:1487	Pisum Sativum Agglutinin	1464:1487	Pisum Sativum Agglutinin (PSA)	1464:1493	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	10	64	theme	signaling	1711:1719	arg1	events					1721:1726	signaling events	1711:1726	signaling events	1711:1726	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	9	65	theme	CCA	1594:1596	arg1	metastasis					1598:1607	CCA metastasis	1594:1607	CCA metastasis	1594:1607	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	6	66	dep	cells	907:911	arg1	KKU-214					926:932	KKU-214	926:932	KKU-214	926:932	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	66	dep	cells	907:911	arg1	KKU-213					914:920	KKU-213	914:920	KKU-213	914:920	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	66	dep	cells	907:911	arg1	cells					907:911	the parental cells	894:911	the parental cells (KKU-213 and KKU-214)	894:933	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	9	67	theme	type	1574:1577	arg1	N-glycans					1579:1587	high mannose type N-glycans	1561:1587	high mannose type N-glycans	1561:1587	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	6	68	dep	cells	985:989	arg1	KKU-214L5					1006:1014	KKU-214L5	1006:1014	KKU-214L5	1006:1014	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	68	dep	cells	985:989	arg1	KKU-213L5					992:1000	KKU-213L5	992:1000	KKU-213L5	992:1000	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	6	68	dep	cells	985:989	arg1	cells					985:989	the highly metastatic cells	963:989	the highly metastatic cells (KKU-213L5 and KKU-214L5)	963:1015	In parallel, the membranous N-glycans of the parental cells (KKU-213 and KKU-214) were compared with those of the highly metastatic cells (KKU-213L5 and KKU-214L5).
29915392	1	69	from	cause	96:100	arg1	patients					121:128	cancer patients	114:128	cancer patients	114:128	The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary.
29915392	5	70	theme	membranous	765:774	arg1	N-glycans					776:784	the membranous N-glycans	761:784	the membranous N-glycans of siOGT-treated cells	761:807	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	10	71	theme	MAN1A1	1847:1852	arg1	expression					1854:1863	MAN1A1 expression	1847:1863	MAN1A1 expression	1847:1863	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	2	72	theme	several	249:255	arg1	glycans					257:263	several glycans	249:263	several glycans that are correlated with poor patient outcome	249:309	During metastasis, cancer cells aberrantly express several glycans that are correlated with poor patient outcome.
29915392	9	73	theme	Pisum	1464:1468	arg1	lectin					1515:1520	a mannose-specific lectin	1496:1520	a mannose-specific lectin	1496:1520	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	9	73	theme	Pisum	1464:1468	arg1	PSA					1490:1492	PSA	1490:1492	PSA	1490:1492	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	9	73	theme	Pisum	1464:1468	arg1	Agglutinin					1478:1487	Pisum Sativum Agglutinin	1464:1487	Pisum Sativum Agglutinin (PSA)	1464:1493	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	9	74	theme	high	1561:1564	arg1	N-glycans					1579:1587	high mannose type N-glycans	1561:1587	high mannose type N-glycans	1561:1587	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	10	75	theme	Akt/Erk	1757:1763	arg1	activation					1743:1752	the activation	1739:1752	the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv)	1739:1925	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	9	76	dep	ability	1376:1382	arg1	invade					1426:1431	invade	1426:1431	invade	1426:1431	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	9	76	dep	ability	1376:1382	arg1	migrate					1414:1420	migrate	1414:1420	migrate	1414:1420	In addition, the ability of highly metastatic cells to migrate and invade was reduced by the presence of Pisum Sativum Agglutinin (PSA), a mannose-specific lectin, further indicating the association of high mannose type N-glycans with CCA metastasis.
29915392	5	77	theme	scramble	823:830	arg1	cells					846:850	scramble siRNA-treated cells	823:850	scramble siRNA-treated cells	823:850	Using an HPLC-Chip/Time-of-Flight (Chip/TOF) MS system, the N-glycans associated with O-GlcNAcylation were identified by comparing the membranous N-glycans of siOGT-treated cells with those of scramble siRNA-treated cells.
29915392	10	78	theme	progression	1655:1665	arg1	mechanism					1624:1632	The molecular mechanism	1610:1632	The molecular mechanism of O-GlcNAc-mediated progression of CCA	1610:1672	The molecular mechanism of O-GlcNAc-mediated progression of CCA was shown to proceed via a series of signaling events, involving the activation of Akt/Erk (i), an increase in FOXO3 phosphorylation (ii), which results in the reduction of MAN1A1 expression (iii) and thus the accumulation of Hex9HexNAc2 N-glycans (iv).
29915392	4	79	theme	acceptor	611:618	arg1	proteins					620:627	the acceptor proteins	607:627	the acceptor proteins	607:627	Global O-GlcNAcylation in CCA cells was depleted using specific siRNA against O-GlcNAc transferase (OGT), which transfers GlcNAc to the acceptor proteins.
28880013	0	0	theme	cell	84:87	arg1	cells					101:105	EGFR-mutated non-small cell lung cancer cells	61:105	EGFR-mutated non-small cell lung cancer cells	61:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	2	1	theme	ligand-1	431:438	arg1	expression					400:409	expression	400:409	expression of programmed death ligand-1 (PD-L1)	400:446	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	5	2	theme	inhibitor	700:708	arg1	osimertinib					723:733	osimertinib	723:733	osimertinib	723:733	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	2	theme	inhibitor	700:708	arg1	tunicamycin					710:720	the N-linked glycosylation inhibitor tunicamycin	673:720	the N-linked glycosylation inhibitor tunicamycin	673:720	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	1	3	theme	third-generation	135:150	arg1	receptor					176:183	third-generation epidermal growth factor receptor	135:183	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	133:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	3	theme	third-generation	135:150	arg1	EGFR					186:189	EGFR	186:189	EGFR	186:189	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	8	4	theme	PD-L1	1546:1550	arg1	degradation					1552:1562	osimertinib-induced PD-L1 degradation	1526:1562	osimertinib-induced PD-L1 degradation	1526:1562	In addition, inhibition of GSK3β by LiCl prevented osimertinib-induced PD-L1 degradation.
28880013	0	5	theme	non-small	74:82	arg1	cells					101:105	EGFR-mutated non-small cell lung cancer cells	61:105	EGFR-mutated non-small cell lung cancer cells	61:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	9	6	from	microenvironment	1760:1775	arg1	patients					1799:1806	EGFR-mutated NSCLC patients	1780:1806	EGFR-mutated NSCLC patients	1780:1806	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	6	7	theme	13.8	1229:1232	arg1	h					1234:1234	h	1234:1234	h	1234:1234	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	1	8	theme	epidermal	152:160	arg1	receptor					176:183	third-generation epidermal growth factor receptor	135:183	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	133:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	8	theme	epidermal	152:160	arg1	EGFR					186:189	EGFR	186:189	EGFR	186:189	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	4	9	from	expression	608:617	arg1	NCI-H1975					627:635	NCI-H1975	627:635	NCI-H1975	627:635	Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells.
28880013	4	9	from	expression	608:617	arg1	cells					648:652	HCC827 cells	641:652	HCC827 cells	641:652	Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells.
28880013	8	10	theme	osimertinib-induced	1526:1544	arg1	degradation					1552:1562	osimertinib-induced PD-L1 degradation	1526:1562	osimertinib-induced PD-L1 degradation	1526:1562	In addition, inhibition of GSK3β by LiCl prevented osimertinib-induced PD-L1 degradation.
28880013	0	11	theme	cancer	94:99	arg1	cells					101:105	EGFR-mutated non-small cell lung cancer cells	61:105	EGFR-mutated non-small cell lung cancer cells	61:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	6	12	theme	transcription	841:853	arg1	processes					871:879	transcription and translation processes	841:879	transcription and translation processes	841:879	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	0	13	theme	lung	89:92	arg1	cells					101:105	EGFR-mutated non-small cell lung cancer cells	61:105	EGFR-mutated non-small cell lung cancer cells	61:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	0	14	from	ligand-1	49:56	arg1	cells					101:105	EGFR-mutated non-small cell lung cancer cells	61:105	EGFR-mutated non-small cell lung cancer cells	61:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	6	15	theme	actinomycin	886:896	arg1	D					898:898	actinomycin D	886:898	actinomycin D	886:898	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	6	16	theme	post-translational	1048:1065	arg1	level					1067:1071	the post-translational level	1044:1071	the post-translational level	1044:1071	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	4	17	theme	HCC827	641:646	arg1	cells					648:652	HCC827 cells	641:652	HCC827 cells	641:652	Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells.
28880013	6	18	dep	h	1234:1234	arg1	to					1236:1237	to	1236:1237	to	1236:1237	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	5	19	from	reduction	807:815	arg1	mRNA					820:823	mRNA	820:823	mRNA	820:823	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	4	20	theme	PD-L1	597:601	arg1	expression					608:617	PD-L1 mRNA expression	597:617	PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells	597:652	Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells.
28880013	1	21	theme	growth	162:167	arg1	receptor					176:183	third-generation epidermal growth factor receptor	135:183	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	133:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	21	theme	growth	162:167	arg1	EGFR					186:189	EGFR	186:189	EGFR	186:189	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	7	22	with	Pretreatment	1301:1312	arg1	MG-132					1346:1351	MG-132	1346:1351	MG-132	1346:1351	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	22	with	Pretreatment	1301:1312	arg1	inhibitors					1334:1343	the proteasome inhibitors	1319:1343	the proteasome inhibitors (MG-132 or bortezomib)	1319:1366	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	22	with	Pretreatment	1301:1312	arg1	bortezomib					1356:1365	bortezomib	1356:1365	bortezomib	1356:1365	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	2	23	theme	programmed	414:423	arg1	PD-L1					441:445	PD-L1	441:445	PD-L1	441:445	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	2	23	theme	programmed	414:423	arg1	ligand-1					431:438	programmed death ligand-1	414:438	programmed death ligand-1 (PD-L1)	414:446	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	9	24	theme	cells	1741:1745	arg1	activity					1727:1734	the immune activity	1716:1734	the immune activity of T cells	1716:1745	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	1	25	theme	factor	169:174	arg1	receptor					176:183	third-generation epidermal growth factor receptor	135:183	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	133:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	25	theme	factor	169:174	arg1	EGFR					186:189	EGFR	186:189	EGFR	186:189	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	9	26	theme	T	1739:1739	arg1	cells					1741:1745	T cells	1739:1745	T cells	1739:1745	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	2	27	theme	death	425:429	arg1	PD-L1					441:445	PD-L1	441:445	PD-L1	441:445	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	2	27	theme	death	425:429	arg1	ligand-1					431:438	programmed death ligand-1	414:438	programmed death ligand-1 (PD-L1)	414:446	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	9	28	theme	PD-L1	1614:1618	arg1	expression					1625:1634	PD-L1 mRNA expression	1614:1634	PD-L1 mRNA expression	1614:1634	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	5	29	theme	N-linked	677:684	arg1	osimertinib					723:733	osimertinib	723:733	osimertinib	723:733	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	29	theme	N-linked	677:684	arg1	tunicamycin					710:720	the N-linked glycosylation inhibitor tunicamycin	673:720	the N-linked glycosylation inhibitor tunicamycin	673:720	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	7	30	theme	proteasome	1323:1332	arg1	MG-132					1346:1351	MG-132	1346:1351	MG-132	1346:1351	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	30	theme	proteasome	1323:1332	arg1	inhibitors					1334:1343	the proteasome inhibitors	1319:1343	the proteasome inhibitors (MG-132 or bortezomib)	1319:1366	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	30	theme	proteasome	1323:1332	arg1	bortezomib					1356:1365	bortezomib	1356:1365	bortezomib	1356:1365	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	31	theme	osimertinib-induced	1380:1398	arg1	degradation					1400:1410	the osimertinib-induced degradation	1376:1410	the osimertinib-induced degradation of PD-L1	1376:1419	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	1	32	theme	receptor	176:183	arg1	TKI					219:221	TKI	219:221	TKI	219:221	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	32	theme	receptor	176:183	arg1	inhibitor					208:216	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor	133:216	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	133:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	32	theme	receptor	176:183	arg1	Osimertinib					108:118	Osimertinib	108:118	Osimertinib (AZD9291)	108:128	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	32	theme	receptor	176:183	arg1	approved					238:245	approved	238:245	approved	238:245	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	2	33	theme	high	385:388	arg1	levels					390:395	high levels	385:395	high levels of expression of programmed death ligand-1 (PD-L1)	385:446	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	6	34	theme	PD-L1	1193:1197	arg1	half-life					1180:1188	the half-life	1176:1188	the half-life of PD-L1	1176:1197	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	2	35	from	patients	326:333	arg1	likely					356:361	likely	356:361	likely	356:361	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	2	35	from	patients	326:333	arg1	mutation					344:351	an EGFR mutation	336:351	an EGFR mutation	336:351	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	6	36	theme	chase	1113:1117	arg1	assay					1119:1123	a cycloheximide chase assay	1097:1123	a cycloheximide chase assay	1097:1123	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	9	37	theme	tumor	1754:1758	arg1	microenvironment					1760:1775	the tumor microenvironment	1750:1775	the tumor microenvironment in EGFR-mutated NSCLC patients	1750:1806	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	5	38	with	Pretreatment	655:666	arg1	osimertinib					723:733	osimertinib	723:733	osimertinib	723:733	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	38	with	Pretreatment	655:666	arg1	tunicamycin					710:720	the N-linked glycosylation inhibitor tunicamycin	673:720	the N-linked glycosylation inhibitor tunicamycin	673:720	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	39	link	N-linked	677:684	arg1	osimertinib					723:733	osimertinib	723:733	osimertinib	723:733	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	39	link	N-linked	677:684	arg1	tunicamycin					710:720	the N-linked glycosylation inhibitor tunicamycin	673:720	the N-linked glycosylation inhibitor tunicamycin	673:720	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	40	theme	PD-L1	775:779	arg1	protein					781:787	new PD-L1 protein	771:787	new PD-L1 protein	771:787	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	41	theme	new	771:773	arg1	protein					781:787	new PD-L1 protein	771:787	new PD-L1 protein	771:787	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	3	42	theme	PD-L1	492:496	arg1	expression					498:507	PD-L1 expression	492:507	PD-L1 expression in human EGFR mutant NSCLC cells	492:540	Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro.
28880013	6	43	theme	translation	859:869	arg1	processes					871:879	transcription and translation processes	841:879	transcription and translation processes	841:879	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	5	44	theme	protein	781:787	arg1	production					757:766	the production	753:766	the production of new PD-L1 protein	753:787	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	0	45	theme	programmed	32:41	arg1	ligand-1					49:56	programmed death ligand-1	32:56	programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells	32:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	9	46	theme	mRNA	1620:1623	arg1	expression					1625:1634	PD-L1 mRNA expression	1614:1634	PD-L1 mRNA expression	1614:1634	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	3	47	theme	mutant	523:528	arg1	cells					536:540	human EGFR mutant NSCLC cells	512:540	human EGFR mutant NSCLC cells	512:540	Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro.
28880013	1	48	theme	tyrosine	192:199	arg1	TKI					219:221	TKI	219:221	TKI	219:221	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	48	theme	tyrosine	192:199	arg1	inhibitor					208:216	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor	133:216	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	133:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	48	theme	tyrosine	192:199	arg1	Osimertinib					108:118	Osimertinib	108:118	Osimertinib (AZD9291)	108:128	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	48	theme	tyrosine	192:199	arg1	approved					238:245	approved	238:245	approved	238:245	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	49	theme	EGFR-mutated	268:279	arg1	NSCLC					309:313	NSCLC	309:313	NSCLC	309:313	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	49	theme	EGFR-mutated	268:279	arg1	cancer					301:306	EGFR-mutated non-small cell lung cancer	268:306	EGFR-mutated non-small cell lung cancer (NSCLC)	268:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	7	50	theme	autophagy	1442:1450	arg1	inhibitor					1429:1437	an inhibitor	1426:1437	an inhibitor of autophagy (chloroquine)	1426:1464	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	50	theme	autophagy	1442:1450	arg1	chloroquine					1453:1463	chloroquine	1453:1463	chloroquine	1453:1463	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	3	51	theme	NSCLC	530:534	arg1	cells					536:540	human EGFR mutant NSCLC cells	512:540	human EGFR mutant NSCLC cells	512:540	Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro.
28880013	1	52	theme	kinase	201:206	arg1	TKI					219:221	TKI	219:221	TKI	219:221	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	52	theme	kinase	201:206	arg1	inhibitor					208:216	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor	133:216	a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	133:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	52	theme	kinase	201:206	arg1	Osimertinib					108:118	Osimertinib	108:118	Osimertinib (AZD9291)	108:128	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	52	theme	kinase	201:206	arg1	approved					238:245	approved	238:245	approved	238:245	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	2	53	theme	expression	400:409	arg1	levels					390:395	high levels	385:395	high levels of expression of programmed death ligand-1 (PD-L1)	385:446	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	1	54	theme	non-small	281:289	arg1	NSCLC					309:313	NSCLC	309:313	NSCLC	309:313	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	54	theme	non-small	281:289	arg1	cancer					301:306	EGFR-mutated non-small cell lung cancer	268:306	EGFR-mutated non-small cell lung cancer (NSCLC)	268:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	9	55	theme	protein	1652:1658	arg1	degradation					1660:1670	its protein degradation	1648:1670	its protein degradation	1648:1670	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	3	56	theme	human	512:516	arg1	cells					536:540	human EGFR mutant NSCLC cells	512:540	human EGFR mutant NSCLC cells	512:540	Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro.
28880013	0	57	theme	death	43:47	arg1	ligand-1					49:56	programmed death ligand-1	32:56	programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells	32:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	1	58	theme	cell	291:294	arg1	NSCLC					309:313	NSCLC	309:313	NSCLC	309:313	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	58	theme	cell	291:294	arg1	cancer					301:306	EGFR-mutated non-small cell lung cancer	268:306	EGFR-mutated non-small cell lung cancer (NSCLC)	268:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	7	59	theme	PD-L1	1415:1419	arg1	degradation					1400:1410	the osimertinib-induced degradation	1376:1410	the osimertinib-induced degradation of PD-L1	1376:1419	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	3	60	theme	EGFR	518:521	arg1	cells					536:540	human EGFR mutant NSCLC cells	512:540	human EGFR mutant NSCLC cells	512:540	Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro.
28880013	9	61	theme	NSCLC	1793:1797	arg1	patients					1799:1806	EGFR-mutated NSCLC patients	1780:1806	EGFR-mutated NSCLC patients	1780:1806	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	1	62	theme	lung	296:299	arg1	NSCLC					309:313	NSCLC	309:313	NSCLC	309:313	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	1	62	theme	lung	296:299	arg1	cancer					301:306	EGFR-mutated non-small cell lung cancer	268:306	EGFR-mutated non-small cell lung cancer (NSCLC)	268:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	6	63	theme	8.6	1239:1241	arg1	h					1234:1234	h	1234:1234	h	1234:1234	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	7	64	dep	inhibitors	1334:1343	arg1	MG-132					1346:1351	MG-132	1346:1351	MG-132	1346:1351	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	64	dep	inhibitors	1334:1343	arg1	inhibitors					1334:1343	the proteasome inhibitors	1319:1343	the proteasome inhibitors (MG-132 or bortezomib)	1319:1366	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	7	64	dep	inhibitors	1334:1343	arg1	bortezomib					1356:1365	bortezomib	1356:1365	bortezomib	1356:1365	Pretreatment with the proteasome inhibitors (MG-132 or bortezomib) blocked the osimertinib-induced degradation of PD-L1, but an inhibitor of autophagy (chloroquine) did not.
28880013	9	65	theme	EGFR-mutated	1780:1791	arg1	patients					1799:1806	EGFR-mutated NSCLC patients	1780:1806	EGFR-mutated NSCLC patients	1780:1806	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
28880013	6	66	theme	cycloheximide	1099:1111	arg1	assay					1119:1123	a cycloheximide chase assay	1097:1123	a cycloheximide chase assay	1097:1123	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	6	67	theme	PD-L1	983:987	arg1	expression					969:978	the expression	965:978	the expression of PD-L1	965:987	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	2	68	from	likely	356:361	arg1	patients					326:333	NSCLC patients	320:333	NSCLC patients	320:333	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	4	69	theme	mRNA	603:606	arg1	expression					608:617	PD-L1 mRNA expression	597:617	PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells	597:652	Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells.
28880013	3	70	from	expression	498:507	arg1	cells					536:540	human EGFR mutant NSCLC cells	512:540	human EGFR mutant NSCLC cells	512:540	Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro.
28880013	8	71	theme	GSK3β	1502:1506	arg1	inhibition					1488:1497	inhibition	1488:1497	inhibition of GSK3β by LiCl	1488:1514	In addition, inhibition of GSK3β by LiCl prevented osimertinib-induced PD-L1 degradation.
28880013	0	72	theme	EGFR-mutated	61:72	arg1	cells					101:105	EGFR-mutated non-small cell lung cancer cells	61:105	EGFR-mutated non-small cell lung cancer cells	61:105	Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells.
28880013	6	73	theme	HCC827	1287:1292	arg1	cells					1294:1298	HCC827 cells	1287:1298	HCC827 cells	1287:1298	After blocking transcription and translation processes with actinomycin D and cycloheximide, respectively, osimertinib continued to reduce the expression of PD-L1, demonstrating that osimertinib might degrade PD-L1 at the post-translational level, which was confirmed by a cycloheximide chase assay, revealing that osimertinib (125 nmol/L) decreased the half-life of PD-L1 from approximately 17.8 h and 13.8 h to 8.6 h and 4.6 h, respectively, in NCI-H1975 and HCC827 cells.
28880013	2	74	theme	EGFR	339:342	arg1	likely					356:361	likely	356:361	likely	356:361	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	2	74	theme	EGFR	339:342	arg1	mutation					344:351	an EGFR mutation	336:351	an EGFR mutation	336:351	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	5	75	theme	glycosylation	686:698	arg1	osimertinib					723:733	osimertinib	723:733	osimertinib	723:733	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	5	75	theme	glycosylation	686:698	arg1	tunicamycin					710:720	the N-linked glycosylation inhibitor tunicamycin	673:720	the N-linked glycosylation inhibitor tunicamycin	673:720	Pretreatment with the N-linked glycosylation inhibitor tunicamycin, osimertinib clearly decreased the production of new PD-L1 protein probably due to a reduction in mRNA.
28880013	1	76	theme	cancer	301:306	arg1	treatment					255:263	the treatment	251:263	the treatment of EGFR-mutated non-small cell lung cancer (NSCLC)	251:314	Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
28880013	2	77	theme	NSCLC	320:324	arg1	patients					326:333	NSCLC patients	320:333	NSCLC patients	320:333	In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1).
28880013	9	78	theme	immune	1720:1725	arg1	activity					1727:1734	the immune activity	1716:1734	the immune activity of T cells	1716:1745	The results demonstrate that osimertinib reduces PD-L1 mRNA expression and induces its protein degradation, suggesting that osimertinib may reactivate the immune activity of T cells in the tumor microenvironment in EGFR-mutated NSCLC patients.
31506438	0	0	theme	outbred	89:95	arg1	line					103:106	an advanced intercross outbred mouse line	66:106	an advanced intercross outbred mouse line	66:106	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	8	1	theme	association	1153:1163	arg1	studies					1165:1171	genetic association studies	1145:1171	genetic association studies	1145:1171	Collectively, our study underlines the importance of including environmental factors in genetic association studies.
31506438	5	2	theme	AIL	648:650	arg1	strains					660:666	the AIL founder strains	644:666	the AIL founder strains	644:666	By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes.
31506438	7	3	theme	intestinal	955:964	arg1	composition					997:1007	intestinal bacterial and fungal community composition	955:1007	intestinal bacterial and fungal community composition	955:1007	Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation.
31506438	0	4	theme	intercross	78:87	arg1	line					103:106	an advanced intercross outbred mouse line	66:106	an advanced intercross outbred mouse line	66:106	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	5	5	theme	founder	652:658	arg1	strains					660:666	the AIL founder strains	644:666	the AIL founder strains	644:666	By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes.
31506438	4	6	theme	trait	585:589	arg1	QTL					597:599	QTL	597:599	QTL	597:599	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	4	6	theme	trait	585:589	arg1	loci					591:594	additional genetic susceptibility quantitative trait loci	538:594	additional genetic susceptibility quantitative trait loci (QTL)	538:600	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	5	7	theme	candidate	708:716	arg1	genes					718:722	few or single candidate genes	694:722	few or single candidate genes	694:722	By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes.
31506438	7	8	theme	genetic	912:918	arg1	susceptibility					920:933	genetic susceptibility	912:933	genetic susceptibility to lupus	912:942	Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation.
31506438	5	9	theme	strains	660:666	arg1	sequencing					630:639	whole-genome sequencing	617:639	whole-genome sequencing of the AIL founder strains	617:666	By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes.
31506438	6	10	theme	given	800:804	arg1	trait					806:810	a given trait	798:810	a given trait	798:810	To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice.
31506438	2	11	theme	phenotypic	298:307	arg1	traits					309:314	phenotypic traits	298:314	phenotypic traits	298:314	However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive.
31506438	0	12	theme	mouse	97:101	arg1	line					103:106	an advanced intercross outbred mouse line	66:106	an advanced intercross outbred mouse line	66:106	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	2	13	theme	interactions	282:293	arg1	impact					255:260	the impact	251:260	the impact of gene-environment interactions on phenotypic traits	251:314	However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive.
31506438	8	14	from	importance	1096:1105	arg1	studies					1165:1171	genetic association studies	1145:1171	genetic association studies	1145:1171	Collectively, our study underlines the importance of including environmental factors in genetic association studies.
31506438	0	15	from	variation	53:61	arg1	line					103:106	an advanced intercross outbred mouse line	66:106	an advanced intercross outbred mouse line	66:106	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	5	16	theme	whole-genome	617:628	arg1	sequencing					630:639	whole-genome sequencing	617:639	whole-genome sequencing of the AIL founder strains	617:666	By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes.
31506438	2	17	theme	gene-environment	265:280	arg1	interactions					282:293	gene-environment interactions	265:293	gene-environment interactions	265:293	However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive.
31506438	1	18	theme	complex	174:180	arg1	interplay					182:190	a complex interplay	172:190	a complex interplay between the environment (e.g. diet) and genetics	172:239	Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics.
31506438	0	19	theme	trait	47:51	arg1	variation					53:61	complex trait variation	39:61	complex trait variation in an advanced intercross outbred mouse line	39:106	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	3	20	theme	different	428:436	arg1	diets					438:442	an autoimmunity-prone intercross line (AIL) three different diets	378:442	an autoimmunity-prone intercross line (AIL) three different diets	378:442	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	8	21	theme	genetic	1145:1151	arg1	studies					1165:1171	genetic association studies	1145:1171	genetic association studies	1145:1171	Collectively, our study underlines the importance of including environmental factors in genetic association studies.
31506438	6	22	theme	genetic	767:773	arg1	predisposition					775:788	genetic predisposition	767:788	genetic predisposition	767:788	To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice.
31506438	6	23	theme	AIL	866:868	arg1	mice					870:873	AIL mice	866:873	AIL mice	866:873	To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice.
31506438	0	24	theme	Gene-diet	0:8	arg1	interactions					10:21	Gene-diet interactions	0:21	Gene-diet interactions	0:21	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	4	25	theme	genetic	549:555	arg1	QTL					597:599	QTL	597:599	QTL	597:599	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	4	25	theme	genetic	549:555	arg1	loci					591:594	additional genetic susceptibility quantitative trait loci	538:594	additional genetic susceptibility quantitative trait loci (QTL)	538:600	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	6	26	theme	similar	838:844	arg1	regimens					854:861	similar dietary regimens	838:861	similar dietary regimens as AIL mice	838:873	To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice.
31506438	3	27	theme	1154	365:368	arg1	mice					370:373	1154 mice	365:373	1154 mice of an autoimmunity-prone intercross line (AIL) three different diets	365:442	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	4	28	theme	additional	538:547	arg1	QTL					597:599	QTL	597:599	QTL	597:599	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	4	28	theme	additional	538:547	arg1	loci					591:594	additional genetic susceptibility quantitative trait loci	538:594	additional genetic susceptibility quantitative trait loci (QTL)	538:600	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	4	29	theme	quantitative	572:583	arg1	QTL					597:599	QTL	597:599	QTL	597:599	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	4	29	theme	quantitative	572:583	arg1	loci					591:594	additional genetic susceptibility quantitative trait loci	538:594	additional genetic susceptibility quantitative trait loci (QTL)	538:600	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	5	30	theme	few	694:696	arg1	genes					718:722	few or single candidate genes	694:722	few or single candidate genes	694:722	By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes.
31506438	6	31	theme	dietary	846:852	arg1	regimens					854:861	similar dietary regimens	838:861	similar dietary regimens as AIL mice	838:873	To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice.
31506438	1	32	theme	Phenotypic	109:118	arg1	variation					120:128	Phenotypic variation	109:128	Phenotypic variation of quantitative traits	109:151	Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics.
31506438	2	33	from	impact	255:260	arg1	traits					309:314	phenotypic traits	298:314	phenotypic traits	298:314	However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive.
31506438	3	34	theme	line	411:414	arg1	diets					438:442	an autoimmunity-prone intercross line (AIL) three different diets	378:442	an autoimmunity-prone intercross line (AIL) three different diets	378:442	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	4	35	theme	susceptibility	557:570	arg1	QTL					597:599	QTL	597:599	QTL	597:599	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	4	35	theme	susceptibility	557:570	arg1	loci					591:594	additional genetic susceptibility quantitative trait loci	538:594	additional genetic susceptibility quantitative trait loci (QTL)	538:600	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	1	36	theme	e.g.	217:220	arg1	environment					204:214	the environment	200:214	the environment (e.g. diet)	200:226	Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics.
31506438	1	36	theme	e.g.	217:220	arg1	diet					222:225	e.g. diet	217:225	e.g. diet	217:225	Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics.
31506438	3	37	theme	diets	438:442	arg1	mice					370:373	1154 mice	365:373	1154 mice of an autoimmunity-prone intercross line (AIL) three different diets	365:442	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	0	38	theme	complex	39:45	arg1	variation					53:61	complex trait variation	39:61	complex trait variation in an advanced intercross outbred mouse line	39:106	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	4	39	theme	traits	519:524	arg1	variability					496:506	the variability	492:506	the variability of complex traits	492:524	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	5	40	theme	single	701:706	arg1	genes					718:722	few or single candidate genes	694:722	few or single candidate genes	694:722	By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes.
31506438	3	41	theme	autoimmunity-prone	381:398	arg1	AIL					417:419	AIL	417:419	AIL	417:419	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	3	41	theme	autoimmunity-prone	381:398	arg1	line					411:414	an autoimmunity-prone intercross line	378:414	an autoimmunity-prone intercross line (AIL) three different diets	378:442	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	4	42	theme	complex	511:517	arg1	traits					519:524	complex traits	511:524	complex traits	511:524	We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL).
31506438	7	43	theme	clinical	1025:1032	arg1	manifestation					1042:1054	clinical disease manifestation	1025:1054	clinical disease manifestation	1025:1054	Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation.
31506438	3	44	theme	intercross	400:409	arg1	AIL					417:419	AIL	417:419	AIL	417:419	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	3	44	theme	intercross	400:409	arg1	line					411:414	an autoimmunity-prone intercross line	378:414	an autoimmunity-prone intercross line (AIL) three different diets	378:442	To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets.
31506438	7	45	theme	disease	1034:1040	arg1	manifestation					1042:1054	clinical disease manifestation	1025:1054	clinical disease manifestation	1025:1054	Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation.
31506438	6	46	theme	NZM2410/J	820:828	arg1	mice					830:833	NZM2410/J mice	820:833	NZM2410/J mice	820:833	To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice.
31506438	7	47	theme	fungal	980:985	arg1	composition					997:1007	intestinal bacterial and fungal community composition	955:1007	intestinal bacterial and fungal community composition	955:1007	Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation.
31506438	8	48	theme	environmental	1120:1132	arg1	factors					1134:1140	including environmental factors	1110:1140	including environmental factors	1110:1140	Collectively, our study underlines the importance of including environmental factors in genetic association studies.
31506438	7	49	theme	community	987:995	arg1	composition					997:1007	intestinal bacterial and fungal community composition	955:1007	intestinal bacterial and fungal community composition	955:1007	Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation.
31506438	1	50	theme	quantitative	133:144	arg1	traits					146:151	quantitative traits	133:151	quantitative traits	133:151	Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics.
31506438	8	51	theme	including	1110:1118	arg1	factors					1134:1140	including environmental factors	1110:1140	including environmental factors	1110:1140	Collectively, our study underlines the importance of including environmental factors in genetic association studies.
31506438	7	52	theme	bacterial	966:974	arg1	composition					997:1007	intestinal bacterial and fungal community composition	955:1007	intestinal bacterial and fungal community composition	955:1007	Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation.
31506438	1	53	theme	traits	146:151	arg1	variation					120:128	Phenotypic variation	109:128	Phenotypic variation of quantitative traits	109:151	Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics.
31506438	0	54	theme	advanced	69:76	arg1	line					103:106	an advanced intercross outbred mouse line	66:106	an advanced intercross outbred mouse line	66:106	Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line.
31506438	8	55	theme	factors	1134:1140	arg1	importance					1096:1105	the importance	1092:1105	the importance of including environmental factors in genetic association studies	1092:1171	Collectively, our study underlines the importance of including environmental factors in genetic association studies.
28008135	3	0	from	enzyme	429:434	arg1	pathway					467:473	the hexosamine biosynthesis pathway	439:473	the hexosamine biosynthesis pathway (HBP)	439:479	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	3	0	from	enzyme	429:434	arg1	HBP					476:478	HBP	476:478	HBP	476:478	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	12	1	theme	targeting	1892:1900	arg1	AMPK					1902:1905	targeting AMPK	1892:1905	targeting AMPK in endothelium	1892:1920	They suggest that targeting AMPK in endothelium might help to ameliorate hyperglycaemia-induced vascular dysfunction associated with metabolic disorders.
28008135	7	2	located	observed	1142:1149	arg2	activity					1100:1107	diminished GFAT activity	1084:1107	diminished GFAT activity	1084:1107	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	7	2	located	observed	1142:1149	arg1	cells					1166:1170	endothelial cells	1154:1170	endothelial cells containing wild-type (WT)-GFAT1	1154:1202	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	7	2	located	observed	1142:1149	arg2	levels					1130:1135	reduced O-GlcNAc levels	1113:1135	reduced O-GlcNAc levels	1113:1135	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	7	3	theme	non-phosphorylatable	1232:1251	arg1	S243A-GFAT1					1253:1263	non-phosphorylatable S243A-GFAT1	1232:1263	non-phosphorylatable S243A-GFAT1	1232:1263	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	12	4	from	AMPK	1902:1905	arg1	endothelium					1910:1920	endothelium	1910:1920	endothelium	1910:1920	They suggest that targeting AMPK in endothelium might help to ameliorate hyperglycaemia-induced vascular dysfunction associated with metabolic disorders.
28008135	3	5	theme	proteins	522:529	arg1	modification					506:517	the modification	502:517	the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc)	502:574	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	1	6	from	Activation	66:75	arg1	cells					131:135	endothelial cells	119:135	endothelial cells	119:135	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	9	7	theme	GFAT1	1608:1612	arg1	phosphorylation					1614:1628	AMPK-mediated GFAT1 phosphorylation	1594:1628	AMPK-mediated GFAT1 phosphorylation	1594:1628	In cells expressing S243A-GFAT1, VEGF-induced sprouting was reduced, suggesting that VEGF relieves the inhibitory action of GFAT1/HBP on angiogenesis via AMPK-mediated GFAT1 phosphorylation.
28008135	5	8	theme	growth	933:938	arg1	factor					940:945	vascular endothelial growth factor	912:945	vascular endothelial growth factor (VEGF)	912:952	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	5	8	theme	growth	933:938	arg1	VEGF					948:951	VEGF	948:951	VEGF	948:951	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	4	9	theme	in	767:768	arg1	approaches					789:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	5	10	theme	GFAT1	961:965	arg1	phosphorylation					967:981	GFAT1 phosphorylation	961:981	GFAT1 phosphorylation at serine 243	961:995	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	4	11	theme	angiogenesis	776:787	arg1	approaches					789:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	4	12	theme	pharmacological	738:752	arg1	approaches					789:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	10	13	theme	sprouting	1701:1709	arg1	impairment					1678:1687	impairment	1678:1687	impairment of vascular sprouting	1678:1709	Activation of GFAT1/HBP by high glucose led to impairment of vascular sprouting, whereas GFAT1 inhibition improved sprouting even if glucose level was high.
28008135	7	14	theme	reduced	1113:1119	arg1	levels					1130:1135	reduced O-GlcNAc levels	1113:1135	reduced O-GlcNAc levels	1113:1135	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	7	15	contain	containing	1172:1181	arg2	-GFAT1					1197:1202	wild-type (WT)-GFAT1	1183:1202	wild-type (WT)-GFAT1	1183:1202	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	7	15	contain	containing	1172:1181	arg1	cells					1166:1170	endothelial cells	1154:1170	endothelial cells containing wild-type (WT)-GFAT1	1154:1202	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	1	16	theme	AMP-activated	80:92	arg1	AMPK					110:113	AMPK	110:113	AMPK	110:113	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	1	16	theme	AMP-activated	80:92	arg1	kinase					102:107	AMP-activated protein kinase	80:107	AMP-activated protein kinase (AMPK)	80:114	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	4	17	theme	cells	687:691	arg1	levels					652:657	O-GlcNAc levels	643:657	O-GlcNAc levels	643:657	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	4	17	theme	cells	687:691	arg1	function					663:670	function	663:670	function	663:670	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	4	18	dep	in	767:768	arg1	vitro					770:774	vitro	770:774	vitro	770:774	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	3	19	dep	enzyme	429:434	arg1	modification					506:517	the modification	502:517	the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc)	502:574	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	9	20	theme	AMPK-mediated	1594:1606	arg1	phosphorylation					1614:1628	AMPK-mediated GFAT1 phosphorylation	1594:1628	AMPK-mediated GFAT1 phosphorylation	1594:1628	In cells expressing S243A-GFAT1, VEGF-induced sprouting was reduced, suggesting that VEGF relieves the inhibitory action of GFAT1/HBP on angiogenesis via AMPK-mediated GFAT1 phosphorylation.
28008135	1	21	theme	protein	94:100	arg1	AMPK					110:113	AMPK	110:113	AMPK	110:113	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	1	21	theme	protein	94:100	arg1	kinase					102:107	AMP-activated protein kinase	80:107	AMP-activated protein kinase (AMPK)	80:114	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	8	22	theme	Pharmacological	1266:1280	arg1	inhibition					1282:1291	Pharmacological inhibition	1266:1291	Pharmacological inhibition	1266:1291	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	5	23	theme	human	831:835	arg1	cells					849:853	primary human endothelial cells	823:853	primary human endothelial cells	823:853	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	10	24	theme	vascular	1692:1699	arg1	sprouting					1701:1709	vascular sprouting	1692:1709	vascular sprouting	1692:1709	Activation of GFAT1/HBP by high glucose led to impairment of vascular sprouting, whereas GFAT1 inhibition improved sprouting even if glucose level was high.
28008135	1	25	theme	kinase	102:107	arg1	Activation					66:75	Activation	66:75	Activation of AMP-activated protein kinase (AMPK) in endothelial cells	66:135	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	11	26	from	role	1845:1848	arg1	angiogenesis					1860:1871	angiogenesis	1860:1871	angiogenesis	1860:1871	Our findings provide novel mechanistic insights into the role of HBP in angiogenesis.
28008135	3	27	theme	hexosamine	443:452	arg1	pathway					467:473	the hexosamine biosynthesis pathway	439:473	the hexosamine biosynthesis pathway (HBP)	439:479	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	3	27	theme	hexosamine	443:452	arg1	HBP					476:478	HBP	476:478	HBP	476:478	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	0	28	theme	GFAT1	0:4	arg1	phosphorylation					6:20	GFAT1 phosphorylation	0:20	GFAT1 phosphorylation by AMPK	0:28	GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis.
28008135	7	29	theme	wild-type	1183:1191	arg1	-GFAT1					1197:1202	wild-type (WT)-GFAT1	1183:1202	wild-type (WT)-GFAT1	1183:1202	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	7	30	dep	wild-type	1183:1191	arg1	WT					1194:1195	WT	1194:1195	WT	1194:1195	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	2	31	theme	fructose-6-phosphate	332:351	arg1	GFAT1					373:377	GFAT1	373:377	GFAT1	373:377	Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate.
28008135	2	31	theme	fructose-6-phosphate	332:351	arg1	amidotransferase					353:368	fructose-6-phosphate amidotransferase 1	332:370	glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate	322:399	Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate.
28008135	3	32	theme	biosynthesis	454:465	arg1	pathway					467:473	the hexosamine biosynthesis pathway	439:473	the hexosamine biosynthesis pathway (HBP)	439:479	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	3	32	theme	biosynthesis	454:465	arg1	HBP					476:478	HBP	476:478	HBP	476:478	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	5	33	theme	endothelial	837:847	arg1	cells					849:853	primary human endothelial cells	823:853	primary human endothelial cells	823:853	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	7	34	theme	diminished	1084:1093	arg1	activity					1100:1107	diminished GFAT activity	1084:1107	diminished GFAT activity	1084:1107	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	10	35	theme	high	1658:1661	arg1	glucose					1663:1669	high glucose	1658:1669	high glucose	1658:1669	Activation of GFAT1/HBP by high glucose led to impairment of vascular sprouting, whereas GFAT1 inhibition improved sprouting even if glucose level was high.
28008135	4	36	theme	O-GlcNAc	643:650	arg1	levels					652:657	O-GlcNAc levels	643:657	O-GlcNAc levels	643:657	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	4	37	theme	genetic	755:761	arg1	approaches					789:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	4	38	theme	present	584:590	arg1	study					592:596	the present study	580:596	the present study	580:596	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	7	39	theme	GFAT	1095:1098	arg1	activity					1100:1107	diminished GFAT activity	1084:1107	diminished GFAT activity	1084:1107	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	1	40	theme	stress	167:172	arg1	protection					174:183	stress protection	167:183	stress protection	167:183	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	4	41	theme	GFAT1	697:701	arg1	phosphorylation					703:717	GFAT1 phosphorylation	697:717	GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches	697:798	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	0	42	theme	VEGF-induced	39:50	arg1	angiogenesis					52:63	VEGF-induced angiogenesis	39:63	VEGF-induced angiogenesis	39:63	GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis.
28008135	2	43	dep	glutamine	322:330	arg1	GFAT1					373:377	GFAT1	373:377	GFAT1	373:377	Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate.
28008135	2	43	dep	glutamine	322:330	arg1	amidotransferase					353:368	fructose-6-phosphate amidotransferase 1	332:370	glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate	322:399	Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate.
28008135	12	44	theme	metabolic	2007:2015	arg1	disorders					2017:2025	metabolic disorders	2007:2025	metabolic disorders	2007:2025	They suggest that targeting AMPK in endothelium might help to ameliorate hyperglycaemia-induced vascular dysfunction associated with metabolic disorders.
28008135	4	45	theme	endothelial	675:685	arg1	cells					687:691	endothelial cells	675:691	endothelial cells	675:691	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
28008135	1	46	theme	underlying	211:220	arg1	mechanisms					222:231	the underlying mechanisms	207:231	the underlying mechanisms	207:231	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	5	47	theme	AMPK	815:818	arg1	Activation					801:810	Activation	801:810	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF)	801:952	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	11	48	theme	mechanistic	1815:1825	arg1	insights					1827:1834	novel mechanistic insights	1809:1834	novel mechanistic insights into the role of HBP in angiogenesis	1809:1871	Our findings provide novel mechanistic insights into the role of HBP in angiogenesis.
28008135	3	49	link	O-linked	534:541	arg1	O-GlcNAc					566:573	O-GlcNAc	566:573	O-GlcNAc	566:573	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	3	49	link	O-linked	534:541	arg1	β-N-acetylglucosamine					543:563	O-linked β-N-acetylglucosamine	534:563	O-linked β-N-acetylglucosamine (O-GlcNAc)	534:574	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	9	50	from	action	1554:1559	arg1	angiogenesis					1577:1588	angiogenesis	1577:1588	angiogenesis	1577:1588	In cells expressing S243A-GFAT1, VEGF-induced sprouting was reduced, suggesting that VEGF relieves the inhibitory action of GFAT1/HBP on angiogenesis via AMPK-mediated GFAT1 phosphorylation.
28008135	8	51	theme	GFAT1	1330:1334	arg1	inhibition					1282:1291	Pharmacological inhibition	1266:1291	Pharmacological inhibition	1266:1291	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	8	51	theme	GFAT1	1330:1334	arg1	down-regulation					1311:1325	siRNA-mediated down-regulation	1296:1325	siRNA-mediated down-regulation	1296:1325	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	3	52	theme	rate-limiting	415:427	arg1	enzyme					429:434	the rate-limiting enzyme	411:434	the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls	411:500	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	3	52	theme	rate-limiting	415:427	arg1	GFAT1					402:406	GFAT1	402:406	GFAT1	402:406	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	5	53	theme	endothelial	921:931	arg1	factor					940:945	vascular endothelial growth factor	912:945	vascular endothelial growth factor (VEGF)	912:952	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	5	53	theme	endothelial	921:931	arg1	VEGF					948:951	VEGF	948:951	VEGF	948:951	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	8	54	theme	negative	1404:1411	arg1	regulator					1413:1421	a negative regulator	1402:1421	a negative regulator of angiogenesis	1402:1437	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	8	54	theme	negative	1404:1411	arg1	GFAT1					1388:1392	GFAT1	1388:1392	GFAT1	1388:1392	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	10	55	theme	GFAT1/HBP	1645:1653	arg1	Activation					1631:1640	Activation	1631:1640	Activation of GFAT1/HBP by high glucose	1631:1669	Activation of GFAT1/HBP by high glucose led to impairment of vascular sprouting, whereas GFAT1 inhibition improved sprouting even if glucose level was high.
28008135	8	56	theme	angiogenesis	1426:1437	arg1	regulator					1413:1421	a negative regulator	1402:1421	a negative regulator of angiogenesis	1402:1437	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	8	56	theme	angiogenesis	1426:1437	arg1	GFAT1					1388:1392	GFAT1	1388:1392	GFAT1	1388:1392	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	9	57	theme	GFAT1/HBP	1564:1572	arg1	action					1554:1559	the inhibitory action	1539:1559	the inhibitory action of GFAT1/HBP on angiogenesis	1539:1588	In cells expressing S243A-GFAT1, VEGF-induced sprouting was reduced, suggesting that VEGF relieves the inhibitory action of GFAT1/HBP on angiogenesis via AMPK-mediated GFAT1 phosphorylation.
28008135	5	58	theme	primary	823:829	arg1	cells					849:853	primary human endothelial cells	823:853	primary human endothelial cells	823:853	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	7	59	theme	AMPK	1067:1070	arg1	activation					1072:1081	AMPK activation	1067:1081	AMPK activation	1067:1081	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	7	60	theme	O-GlcNAc	1121:1128	arg1	levels					1130:1135	reduced O-GlcNAc levels	1113:1135	reduced O-GlcNAc levels	1113:1135	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	9	61	theme	inhibitory	1543:1552	arg1	action					1554:1559	the inhibitory action	1539:1559	the inhibitory action of GFAT1/HBP on angiogenesis	1539:1588	In cells expressing S243A-GFAT1, VEGF-induced sprouting was reduced, suggesting that VEGF relieves the inhibitory action of GFAT1/HBP on angiogenesis via AMPK-mediated GFAT1 phosphorylation.
28008135	1	62	theme	endothelial	119:129	arg1	cells					131:135	endothelial cells	119:135	endothelial cells	119:135	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	12	63	theme	vascular	1970:1977	arg1	dysfunction					1979:1989	hyperglycaemia-induced vascular dysfunction	1947:1989	hyperglycaemia-induced vascular dysfunction associated with metabolic disorders	1947:2025	They suggest that targeting AMPK in endothelium might help to ameliorate hyperglycaemia-induced vascular dysfunction associated with metabolic disorders.
28008135	5	64	from	Activation	801:810	arg1	cells					849:853	primary human endothelial cells	823:853	primary human endothelial cells	823:853	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	2	65	theme	phosphoproteomic	281:296	arg1	analysis					298:305	a label-free phosphoproteomic analysis	268:305	a label-free phosphoproteomic analysis	268:305	Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate.
28008135	8	66	theme	siRNA-mediated	1296:1309	arg1	down-regulation					1311:1325	siRNA-mediated down-regulation	1296:1325	siRNA-mediated down-regulation	1296:1325	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	3	67	theme	such	488:491	arg1	controls					493:500	such controls	488:500	such controls	488:500	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	5	68	theme	vascular	912:919	arg1	factor					940:945	vascular endothelial growth factor	912:945	vascular endothelial growth factor (VEGF)	912:952	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	5	68	theme	vascular	912:919	arg1	VEGF					948:951	VEGF	948:951	VEGF	948:951	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	12	69	theme	hyperglycaemia-induced	1947:1968	arg1	dysfunction					1979:1989	hyperglycaemia-induced vascular dysfunction	1947:1989	hyperglycaemia-induced vascular dysfunction associated with metabolic disorders	1947:2025	They suggest that targeting AMPK in endothelium might help to ameliorate hyperglycaemia-induced vascular dysfunction associated with metabolic disorders.
28008135	11	70	theme	novel	1809:1813	arg1	insights					1827:1834	novel mechanistic insights	1809:1834	novel mechanistic insights into the role of HBP in angiogenesis	1809:1871	Our findings provide novel mechanistic insights into the role of HBP in angiogenesis.
28008135	2	71	theme	label-free	270:279	arg1	analysis					298:305	a label-free phosphoproteomic analysis	268:305	a label-free phosphoproteomic analysis	268:305	Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate.
28008135	3	72	theme	O-linked	534:541	arg1	O-GlcNAc					566:573	O-GlcNAc	566:573	O-GlcNAc	566:573	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	3	72	theme	O-linked	534:541	arg1	β-N-acetylglucosamine					543:563	O-linked β-N-acetylglucosamine	534:563	O-linked β-N-acetylglucosamine (O-GlcNAc)	534:574	GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc).
28008135	11	73	theme	HBP	1853:1855	arg1	role					1845:1848	the role	1841:1848	the role of HBP in angiogenesis	1841:1871	Our findings provide novel mechanistic insights into the role of HBP in angiogenesis.
28008135	10	74	theme	GFAT1	1720:1724	arg1	inhibition					1726:1735	GFAT1 inhibition	1720:1735	GFAT1 inhibition	1720:1735	Activation of GFAT1/HBP by high glucose led to impairment of vascular sprouting, whereas GFAT1 inhibition improved sprouting even if glucose level was high.
28008135	10	75	theme	glucose	1764:1770	arg1	level					1772:1776	glucose level	1764:1776	glucose level	1764:1776	Activation of GFAT1/HBP by high glucose led to impairment of vascular sprouting, whereas GFAT1 inhibition improved sprouting even if glucose level was high.
28008135	5	76	theme	5-aminoimidazole-4-carboxamide	858:887	arg1	AICAR					899:903	AICAR	899:903	AICAR	899:903	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	5	76	theme	5-aminoimidazole-4-carboxamide	858:887	arg1	riboside					889:896	5-aminoimidazole-4-carboxamide riboside	858:896	5-aminoimidazole-4-carboxamide riboside (AICAR)	858:904	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	1	77	theme	energy	147:152	arg1	homeostasis					154:164	energy homeostasis	147:164	energy homeostasis	147:164	Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood.
28008135	5	78	from	serine	986:991	arg1	phosphorylation					967:981	GFAT1 phosphorylation	961:981	GFAT1 phosphorylation at serine 243	961:995	Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243.
28008135	7	79	theme	endothelial	1154:1164	arg1	cells					1166:1170	endothelial cells	1154:1170	endothelial cells containing wild-type (WT)-GFAT1	1154:1202	Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1.
28008135	9	80	theme	VEGF-induced	1473:1484	arg1	sprouting					1486:1494	VEGF-induced sprouting	1473:1494	VEGF-induced sprouting	1473:1494	In cells expressing S243A-GFAT1, VEGF-induced sprouting was reduced, suggesting that VEGF relieves the inhibitory action of GFAT1/HBP on angiogenesis via AMPK-mediated GFAT1 phosphorylation.
28008135	2	81	theme	AMPK	386:389	arg1	substrate					391:399	an AMPK substrate	383:399	an AMPK substrate	383:399	Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate.
28008135	8	82	theme	VEGF-induced	1348:1359	arg1	sprouting					1361:1369	VEGF-induced sprouting	1348:1369	VEGF-induced sprouting	1348:1369	Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis.
28008135	4	83	theme	biochemical	725:735	arg1	approaches					789:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	biochemical, pharmacological, genetic and in vitro angiogenesis approaches	725:798	In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches.
30395637	9	0	theme	germline-reverted	1684:1700	arg1	antibodies					1702:1711	the germline-reverted antibodies	1680:1711	the germline-reverted antibodies	1680:1711	Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K.
30395637	6	1	theme	subtype	1358:1364	arg1	C					1366:1366	subtype C	1358:1366	subtype C	1358:1366	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	6	1	theme	subtype	1358:1364	arg1	transmitted/founder					1369:1387	transmitted/founder	1369:1387	transmitted/founder	1369:1387	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	2	2	theme	trimeric	290:297	arg1	glycoprotein					320:331	trimeric HIV-1 envelope (Env) glycoprotein	290:331	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	1	3	theme	antibody	150:157	arg1	priority					186:193	a high priority	179:193	a high priority for effective HIV-1 vaccination	179:225	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	1	3	theme	antibody	150:157	arg1	induction					166:174	Broadly neutralizing antibody (bnAb) induction	129:174	Broadly neutralizing antibody (bnAb) induction	129:174	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	4	4	theme	Env	909:911	arg1	trimers					913:919	functional Env trimers	898:919	functional Env trimers	898:919	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	6	5	theme	N-linked	1235:1242	arg1	glycans					1244:1250	remaining N-linked glycans	1225:1250	remaining N-linked glycans that are otherwise processed into larger complex-type glycans	1225:1312	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	6	6	theme	426c	1330:1333	arg1	virus					1351:1355	HIV-1 426c Env-pseudotyped virus	1324:1355	HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization	1324:1425	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	2	7	theme	Env	315:317	arg1	glycoprotein					320:331	trimeric HIV-1 envelope (Env) glycoprotein	290:331	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	1	8	theme	HIV-1	209:213	arg1	vaccination					215:225	effective HIV-1 vaccination	199:225	effective HIV-1 vaccination	199:225	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	10	9	theme	early	1956:1960	arg1	precursors					1962:1971	vaccine-elicited early precursors	1939:1971	vaccine-elicited early precursors of this class of bnAbs	1939:1994	These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
30395637	6	10	theme	near	1430:1433	arg1	forms					1444:1448	near germline forms	1430:1448	near germline forms of VRC01-class bnAbs	1430:1469	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	2	11	theme	envelope	305:312	arg1	glycoprotein					320:331	trimeric HIV-1 envelope (Env) glycoprotein	290:331	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	12	from	infection	493:501	arg1	models					513:518	animal models	506:518	animal models	506:518	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	7	13	theme	glycan	1480:1485	arg1	modification					1487:1498	Neither glycan modification	1472:1498	Neither glycan modification	1472:1498	Neither glycan modification alone rendered the virus susceptible to neutralization.
30395637	6	14	theme	susceptible	1397:1407	arg1	virus					1351:1355	HIV-1 426c Env-pseudotyped virus	1324:1355	HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization	1324:1425	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	3	15	theme	bnAbs	610:614	arg1	forms					589:593	germline-reverted forms	571:593	germline-reverted forms of VRC01-class bnAbs	571:614	Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages.
30395637	5	16	theme	trimer	974:979	arg1	engagement					981:990	functional Env trimer engagement	959:990	functional Env trimer engagement of VRC01-class naïve B cell receptors	959:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	6	17	theme	complex-type	1293:1304	arg1	glycans					1306:1312	larger complex-type glycans	1286:1312	larger complex-type glycans	1286:1312	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	5	18	theme	B	1013:1013	arg1	receptors					1020:1028	VRC01-class naïve B cell receptors	995:1028	VRC01-class naïve B cell receptors	995:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	10	19	theme	bnAbs	1990:1994	arg1	class					1981:1985	this class	1976:1985	this class of bnAbs	1976:1994	These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
30395637	0	20	theme	germline-reverted	66:82	arg1	antibodies					117:126	germline-reverted VRC01-class broadly neutralizing antibodies	66:126	germline-reverted VRC01-class broadly neutralizing antibodies	66:126	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.
30395637	2	21	theme	binding	266:272	arg1	site					274:277	the CD4 binding site	258:277	the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes	258:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	21	theme	binding	266:272	arg1	spikes					333:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	21	theme	binding	266:272	arg1	CD4bs					280:284	CD4bs	280:284	CD4bs	280:284	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	1	22	theme	high	181:184	arg1	priority					186:193	a high priority	179:193	a high priority for effective HIV-1 vaccination	179:225	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	1	22	theme	high	181:184	arg1	induction					166:174	Broadly neutralizing antibody (bnAb) induction	129:174	Broadly neutralizing antibody (bnAb) induction	129:174	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	4	23	theme	virus	783:787	arg1	neutralization					789:802	virus neutralization	783:802	Env antigen binding but not virus neutralization	755:802	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	5	24	theme	cell	1015:1018	arg1	receptors					1020:1028	VRC01-class naïve B cell receptors	995:1028	VRC01-class naïve B cell receptors	995:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	6	25	link	N-linked	1235:1242	arg1	glycans					1244:1250	remaining N-linked glycans	1225:1250	remaining N-linked glycans that are otherwise processed into larger complex-type glycans	1225:1312	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	6	26	theme	VRC01-class	1453:1463	arg1	bnAbs					1465:1469	VRC01-class bnAbs	1453:1469	VRC01-class bnAbs	1453:1469	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	8	27	theme	VRC01	1630:1634	arg1	potency					1612:1618	the potency	1608:1618	the potency of mature VRC01 against wildtype viruses	1608:1659	The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses.
30395637	5	28	theme	virus	1039:1043	arg1	surrogates					1096:1105	surrogates	1096:1105	surrogates for the interaction	1096:1125	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	5	28	theme	virus	1039:1043	arg1	neutralization					1045:1058	virus neutralization	1039:1058	virus neutralization	1039:1058	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	5	28	theme	virus	1039:1043	arg1	antibodies					1082:1091	germline-reverted antibodies	1064:1091	germline-reverted antibodies	1064:1091	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	6	29	theme	subset	1151:1156	arg1	deletion					1137:1144	Targeted deletion	1128:1144	Targeted deletion	1128:1144	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	8	30	theme	wildtype	1644:1651	arg1	viruses					1653:1659	wildtype viruses	1644:1659	wildtype viruses	1644:1659	The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses.
30395637	4	31	theme	antigen	759:765	arg1	binding					767:773	Env antigen binding	755:773	Env antigen binding but not virus neutralization	755:802	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	0	32	theme	HIV-1	0:4	arg1	modifications					22:34	HIV-1 envelope glycan modifications	0:34	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies	0:126	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.
30395637	5	33	theme	naïve	1007:1011	arg1	receptors					1020:1028	VRC01-class naïve B cell receptors	995:1028	VRC01-class naïve B cell receptors	995:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	2	34	theme	neutralization	432:445	arg1	potency					421:427	potency	421:427	potency	421:427	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	34	theme	neutralization	432:445	arg1	breadth					409:415	their extraordinary breadth	389:415	their extraordinary breadth	389:415	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	34	theme	neutralization	432:445	arg1	ability					466:472	their ability to protect against infection in animal models	460:518	their ability to protect against infection in animal models	460:518	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	0	35	theme	glycan	15:20	arg1	modifications					22:34	HIV-1 envelope glycan modifications	0:34	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies	0:126	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.
30395637	1	36	theme	neutralizing	137:148	arg1	bnAb					160:163	bnAb	160:163	bnAb	160:163	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	1	36	theme	neutralizing	137:148	arg1	antibody					150:157	Broadly neutralizing antibody	129:157	Broadly neutralizing antibody (bnAb) induction	129:174	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	6	37	theme	Targeted	1128:1135	arg1	deletion					1137:1144	Targeted deletion	1128:1144	Targeted deletion	1128:1144	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	4	38	theme	germline-reverted	848:864	arg1	binding					887:893	germline-reverted VRC01-class antibody binding	848:893	germline-reverted VRC01-class antibody binding to functional Env trimers	848:919	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	4	39	theme	antibody	878:885	arg1	binding					887:893	germline-reverted VRC01-class antibody binding	848:893	germline-reverted VRC01-class antibody binding to functional Env trimers	848:919	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	9	40	theme	VRC01	1740:1744	arg1	mutation					1757:1764	the known VRC01 resistance mutation	1730:1764	the known VRC01 resistance mutation	1730:1764	Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K.
30395637	9	40	theme	VRC01	1740:1744	arg1	D279K					1767:1771	D279K	1767:1771	D279K	1767:1771	Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K.
30395637	10	41	theme	class	1981:1985	arg1	precursors					1962:1971	vaccine-elicited early precursors	1939:1971	vaccine-elicited early precursors of this class of bnAbs	1939:1994	These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
30395637	2	42	gly	glycoprotein	320:331	arg1	glycoprotein					320:331	trimeric HIV-1 envelope (Env) glycoprotein	290:331	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	43	theme	VRC01-class	228:238	arg1	bnAbs					240:244	VRC01-class bnAbs	228:244	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes	228:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	44	theme	spikes	333:338	arg1	site					274:277	the CD4 binding site	258:277	the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes	258:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	44	theme	spikes	333:338	arg1	spikes					333:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	44	theme	spikes	333:338	arg1	CD4bs					280:284	CD4bs	280:284	CD4bs	280:284	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	3	45	theme	correct	685:691	arg1	lineages					702:709	the correct antibody lineages	681:709	the correct antibody lineages	681:709	Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages.
30395637	8	46	from	potency	1560:1566	arg1	cases					1594:1598	some cases	1589:1598	some cases	1589:1598	The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses.
30395637	6	47	dep	virus	1351:1355	arg1	C					1366:1366	subtype C	1358:1366	subtype C	1358:1366	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	6	47	dep	virus	1351:1355	arg1	transmitted/founder					1369:1387	transmitted/founder	1369:1387	transmitted/founder	1369:1387	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	6	48	theme	N-glycans	1161:1169	arg1	subset					1151:1156	a subset	1149:1156	a subset of N-glycans bordering the CD4bs	1149:1189	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	2	49	theme	HIV-1	299:303	arg1	glycoprotein					320:331	trimeric HIV-1 envelope (Env) glycoprotein	290:331	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	10	50	theme	vaccine-elicited	1939:1954	arg1	precursors					1962:1971	vaccine-elicited early precursors	1939:1971	vaccine-elicited early precursors of this class of bnAbs	1939:1994	These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
30395637	6	51	theme	glycans	1244:1250	arg1	enrichment					1211:1220	Man5 enrichment	1206:1220	Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans	1206:1312	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	10	52	theme	neutralization-based	1898:1917	arg1	strategy					1919:1926	a neutralization-based strategy	1896:1926	a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs	1896:1994	These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
30395637	6	53	theme	Env-pseudotyped	1335:1349	arg1	virus					1351:1355	HIV-1 426c Env-pseudotyped virus	1324:1355	HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization	1324:1425	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	3	54	theme	forms	589:593	arg1	binding					560:566	the binding	556:566	the binding of germline-reverted forms of VRC01-class bnAbs	556:614	Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages.
30395637	1	55	theme	effective	199:207	arg1	vaccination					215:225	effective HIV-1 vaccination	199:225	effective HIV-1 vaccination	199:225	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	4	56	theme	functional	898:907	arg1	trimers					913:919	functional Env trimers	898:919	functional Env trimers	898:919	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	6	57	theme	remaining	1225:1233	arg1	glycans					1244:1250	remaining N-linked glycans	1225:1250	remaining N-linked glycans that are otherwise processed into larger complex-type glycans	1225:1312	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	6	58	theme	germline	1435:1442	arg1	forms					1444:1448	near germline forms	1430:1448	near germline forms of VRC01-class bnAbs	1430:1469	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	5	59	theme	functional	959:968	arg1	engagement					981:990	functional Env trimer engagement	959:990	functional Env trimer engagement of VRC01-class naïve B cell receptors	959:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	2	60	theme	CD4	262:264	arg1	site					274:277	the CD4 binding site	258:277	the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes	258:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	60	theme	CD4	262:264	arg1	spikes					333:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	60	theme	CD4	262:264	arg1	CD4bs					280:284	CD4bs	280:284	CD4bs	280:284	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	8	61	theme	neutralization	1571:1584	arg1	potency					1560:1566	The potency	1556:1566	The potency of neutralization in some cases	1556:1598	The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses.
30395637	3	62	theme	VRC01-class	598:608	arg1	bnAbs					610:614	VRC01-class bnAbs	598:614	VRC01-class bnAbs	598:614	Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages.
30395637	5	63	theme	Env	970:972	arg1	engagement					981:990	functional Env trimer engagement	959:990	functional Env trimer engagement of VRC01-class naïve B cell receptors	959:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	6	64	theme	larger	1286:1291	arg1	glycans					1306:1312	larger complex-type glycans	1286:1312	larger complex-type glycans	1286:1312	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	4	65	theme	glycans	739:745	arg1	subset					723:728	a subset	721:728	a subset of these glycans	721:745	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	0	66	theme	VRC01-class	84:94	arg1	antibodies					117:126	germline-reverted VRC01-class broadly neutralizing antibodies	66:126	germline-reverted VRC01-class broadly neutralizing antibodies	66:126	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.
30395637	2	67	theme	animal	506:511	arg1	models					513:518	animal models	506:518	animal models	506:518	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	0	68	theme	neutralizing	104:115	arg1	antibodies					117:126	germline-reverted VRC01-class broadly neutralizing antibodies	66:126	germline-reverted VRC01-class broadly neutralizing antibodies	66:126	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.
30395637	8	69	theme	mature	1623:1628	arg1	VRC01					1630:1634	mature VRC01	1623:1634	mature VRC01	1623:1634	The potency of neutralization in some cases rivaled the potency of mature VRC01 against wildtype viruses.
30395637	6	70	theme	bnAbs	1465:1469	arg1	forms					1444:1448	near germline forms	1430:1448	near germline forms of VRC01-class bnAbs	1430:1469	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	5	71	theme	receptors	1020:1028	arg1	engagement					981:990	functional Env trimer engagement	959:990	functional Env trimer engagement of VRC01-class naïve B cell receptors	959:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	3	72	theme	germline-reverted	571:587	arg1	forms					589:593	germline-reverted forms	571:593	germline-reverted forms of VRC01-class bnAbs	571:614	Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages.
30395637	2	73	theme	glycoprotein	320:331	arg1	spikes					333:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	trimeric HIV-1 envelope (Env) glycoprotein spikes	290:338	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	2	74	theme	extraordinary	395:407	arg1	breadth					409:415	their extraordinary breadth	389:415	their extraordinary breadth	389:415	VRC01-class bnAbs that target the CD4 binding site (CD4bs) of trimeric HIV-1 envelope (Env) glycoprotein spikes are particularly attractive to elicit because of their extraordinary breadth and potency of neutralization in vitro and their ability to protect against infection in animal models.
30395637	0	75	theme	envelope	6:13	arg1	modifications					22:34	HIV-1 envelope glycan modifications	0:34	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies	0:126	HIV-1 envelope glycan modifications that permit neutralization by germline-reverted VRC01-class broadly neutralizing antibodies.
30395637	5	76	theme	VRC01-class	995:1005	arg1	receptors					1020:1028	VRC01-class naïve B cell receptors	995:1028	VRC01-class naïve B cell receptors	995:1028	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	4	77	theme	Env	755:757	arg1	binding					767:773	Env antigen binding	755:773	Env antigen binding but not virus neutralization	755:802	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	1	78	theme	Broadly	129:135	arg1	bnAb					160:163	bnAb	160:163	bnAb	160:163	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	1	78	theme	Broadly	129:135	arg1	antibody					150:157	Broadly neutralizing antibody	129:157	Broadly neutralizing antibody (bnAb) induction	129:174	Broadly neutralizing antibody (bnAb) induction is a high priority for effective HIV-1 vaccination.
30395637	6	79	theme	HIV-1	1324:1328	arg1	virus					1351:1355	HIV-1 426c Env-pseudotyped virus	1324:1355	HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization	1324:1425	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	3	80	theme	early	654:658	arg1	events					660:665	early events	654:665	early events	654:665	Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages.
30395637	9	81	theme	known	1734:1738	arg1	mutation					1757:1764	the known VRC01 resistance mutation	1730:1764	the known VRC01 resistance mutation	1730:1764	Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K.
30395637	9	81	theme	known	1734:1738	arg1	D279K					1767:1771	D279K	1767:1771	D279K	1767:1771	Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K.
30395637	6	82	theme	Man5	1206:1209	arg1	enrichment					1211:1220	Man5 enrichment	1206:1220	Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans	1206:1312	Targeted deletion of a subset of N-glycans bordering the CD4bs, combined with Man5 enrichment of remaining N-linked glycans that are otherwise processed into larger complex-type glycans, rendered HIV-1 426c Env-pseudotyped virus (subtype C, transmitted/founder) highly susceptible to neutralization by near germline forms of VRC01-class bnAbs.
30395637	3	83	theme	antibody	693:700	arg1	lineages					702:709	the correct antibody lineages	681:709	the correct antibody lineages	681:709	Glycans bordering the CD4bs impede the binding of germline-reverted forms of VRC01-class bnAbs and therefore constitute a barrier to early events in initiating the correct antibody lineages.
30395637	4	84	theme	VRC01-class	866:876	arg1	binding					887:893	germline-reverted VRC01-class antibody binding	848:893	germline-reverted VRC01-class antibody binding to functional Env trimers	848:919	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	9	85	theme	resistance	1746:1755	arg1	mutation					1757:1764	the known VRC01 resistance mutation	1730:1764	the known VRC01 resistance mutation	1730:1764	Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K.
30395637	9	85	theme	resistance	1746:1755	arg1	D279K					1767:1771	D279K	1767:1771	D279K	1767:1771	Neutralization by the germline-reverted antibodies was abrogated by the known VRC01 resistance mutation, D279K.
30395637	10	86	theme	restrictions	1822:1833	arg1	understanding					1801:1813	our understanding	1797:1813	our understanding of the restrictions imposed by glycans	1797:1852	These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
30395637	5	87	theme	germline-reverted	1064:1080	arg1	surrogates					1096:1105	surrogates	1096:1105	surrogates for the interaction	1096:1125	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	5	87	theme	germline-reverted	1064:1080	arg1	neutralization					1045:1058	virus neutralization	1039:1058	virus neutralization	1039:1058	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	5	87	theme	germline-reverted	1064:1080	arg1	antibodies					1082:1091	germline-reverted antibodies	1064:1091	germline-reverted antibodies	1064:1091	We investigated the requirements for functional Env trimer engagement of VRC01-class naïve B cell receptors by using virus neutralization and germline-reverted antibodies as surrogates for the interaction.
30395637	4	88	theme	additional	821:830	arg1	barriers					832:839	additional barriers	821:839	additional barriers	821:839	Deleting a subset of these glycans permits Env antigen binding but not virus neutralization, suggesting that additional barriers impede germline-reverted VRC01-class antibody binding to functional Env trimers.
30395637	10	89	theme	VRC01-class	1867:1877	arg1	bnAbs					1879:1883	VRC01-class bnAbs	1867:1883	VRC01-class bnAbs	1867:1883	These findings improve our understanding of the restrictions imposed by glycans in eliciting VRC01-class bnAbs and enable a neutralization-based strategy to monitor vaccine-elicited early precursors of this class of bnAbs.
31170332	3	0	attach	derived	469:475	arg2	instrument					430:439	A genetic instrument	420:439	A genetic instrument	420:439	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	0	attach	derived	469:475	arg1	meta-analysis					520:532	a genomewide association study (GWAS) meta-analysis	482:532	a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals	482:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	1	theme	study	507:511	arg1	meta-analysis					520:532	a genomewide association study (GWAS) meta-analysis	482:532	a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals	482:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	6	2	theme	neck	1405:1408	arg1	BMD					1410:1412	femoral neck BMD	1397:1412	femoral neck BMD	1397:1412	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	4	3	theme	novel	829:833	arg1	loci					852:855	two novel serum sclerostin loci	825:855	two novel serum sclerostin loci	825:855	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	3	theme	novel	829:833	arg1	change					893:898	B4GALNT3 (standard deviation [SD]) change	858:898	B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 )	858:954	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	3	theme	novel	829:833	arg1	GALNT1					960:965	GALNT1	960:965	GALNT1	960:965	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	7	4	theme	B4GALNT3	1667:1674	arg1	locus					1676:1680	the B4GALNT3 locus	1663:1680	the B4GALNT3 locus	1663:1680	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	3	5	theme	mineral	702:708	arg1	eBMD					719:722	eBMD	719:722	eBMD	719:722	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	5	theme	mineral	702:708	arg1	density					710:716	estimated bone mineral density	687:716	estimated bone mineral density (eBMD)	687:723	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	4	6	dep	allele	920:925	arg1	β = 0.20					928:935	β = 0.20	928:935	β = 0.20	928:935	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	6	dep	allele	920:925	arg1	p = 4.6 × 10-49					938:952	p = 4.6 × 10-49	938:952	p = 4.6 × 10-49	938:952	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	3	7	theme	serum	537:541	arg1	sclerostin					543:552	serum sclerostin	537:552	serum sclerostin	537:552	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	8	from	density	648:654	arg1	GEFOS					677:681	GEFOS	677:681	GEFOS	677:681	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	9	theme	estimated	687:695	arg1	eBMD					719:722	eBMD	719:722	eBMD	719:722	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	9	theme	estimated	687:695	arg1	density					710:716	estimated bone mineral density	687:716	estimated bone mineral density (eBMD)	687:723	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	8	10	theme	lower	1863:1867	arg1	BMD					1869:1871	lower BMD	1863:1871	lower BMD	1863:1871	Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk.
31170332	7	11	theme	genetic	1640:1646	arg1	signals					1648:1654	common genetic signals	1633:1654	common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%)	1633:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	2	12	theme	functional	312:321	arg1	role					323:326	a functional role	310:326	a functional role	310:326	Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR).
31170332	6	13	dep	-0.05	1464:1468	arg1	to					1461:1462	to	1461:1462	to	1461:1462	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	3	14	from	density	710:716	arg1	GEFOS					677:681	GEFOS	677:681	GEFOS	677:681	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	6	15	theme	interval	1441:1448	arg1	[CI					1450:1452	β = -0.12, 95% confidence interval [CI	1415:1452	β = -0.12, 95% confidence interval [CI	1415:1452	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	15	theme	interval	1441:1448	arg1	sclerostin					1382:1391	serum sclerostin	1376:1391	serum sclerostin	1376:1391	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	1	16	theme	local	203:207	arg1	role					209:212	an important local role	190:212	an important local role	190:212	In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading.
31170332	11	17	theme	Research	2129:2136	arg1	Journal					2101:2107	Journal	2101:2107	Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.	2101:2173	Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
31170332	8	18	theme	greater	1877:1883	arg1	risk					1894:1897	greater fracture risk	1877:1897	greater fracture risk	1877:1897	Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk.
31170332	4	19	theme	sclerostin	841:850	arg1	loci					852:855	two novel serum sclerostin loci	825:855	two novel serum sclerostin loci	825:855	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	19	theme	sclerostin	841:850	arg1	change					893:898	B4GALNT3 (standard deviation [SD]) change	858:898	B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 )	858:954	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	19	theme	sclerostin	841:850	arg1	GALNT1					960:965	GALNT1	960:965	GALNT1	960:965	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	3	20	theme	heel	728:731	arg1	ultrasound					733:742	heel ultrasound	728:742	heel ultrasound (n = 426,824)	728:756	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	20	theme	heel	728:731	arg1	n = 426,795					777:787	n = 426,795	777:787	n = 426,795	777:787	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	20	theme	heel	728:731	arg1	n = 426,824					745:755	n = 426,824	745:755	n = 426,824	745:755	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	5	21	link	O-linked	1222:1229	arg1	glycosylation					1231:1243	mucin-type O-linked glycosylation	1211:1243	mucin-type O-linked glycosylation	1211:1243	B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation.
31170332	6	22	theme	fracture	1549:1556	arg1	risk					1558:1561	fracture risk	1549:1561	fracture risk (β = 0.11, 95% CI 0.01 to 0.21)	1549:1593	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	22	theme	fracture	1549:1556	arg1	CI					1578:1579	β = 0.11, 95% CI 0.01 to 0.21	1564:1592	CI	1578:1579	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	3	23	theme	fracture	762:769	arg1	risk					771:774	fracture risk	762:774	fracture risk	762:774	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	8	24	theme	sclerostin	1821:1830	arg1	levels					1832:1837	higher sclerostin levels	1814:1837	higher sclerostin levels	1814:1837	Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk.
31170332	3	25	theme	femoral	622:628	arg1	BMD					657:659	BMD; n = 32,744	657:671	BMD; n = 32,744	657:671	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	25	theme	femoral	622:628	arg1	density					648:654	femoral neck bone mineral density	622:654	femoral neck bone mineral density (BMD; n = 32,744) in GEFOS	622:681	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	8	26	theme	fracture	1885:1892	arg1	risk					1894:1897	greater fracture risk	1877:1897	greater fracture risk	1877:1897	Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk.
31170332	5	27	theme	O-linked	1222:1229	arg1	glycosylation					1231:1243	mucin-type O-linked glycosylation	1211:1243	mucin-type O-linked glycosylation	1211:1243	B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation.
31170332	0	28	theme	Circulating	63:73	arg1	Levels					86:91	Circulating Sclerostin Levels	63:91	Circulating Sclerostin Levels	63:91	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	1	29	from	osteocyte-derived	162:178	arg1	bone					135:138	bone	135:138	bone	135:138	In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading.
31170332	7	30	from	expression	1738:1747	arg1	%					1784:1784	probability >99%	1769:1784	probability >99%	1769:1784	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	7	30	from	expression	1738:1747	arg1	tissue					1761:1766	arterial tissue	1752:1766	arterial tissue (probability >99%)	1752:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	3	31	from	meta-analysis	520:532	arg1	individuals					581:591	10,584 European-descent individuals	557:591	10,584 European-descent individuals	557:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	0	32	theme	Levels	86:91	arg1	Influence					50:58	a Causal Influence	41:58	a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures	41:129	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	6	33	theme	positive	1522:1529	arg1	relationship					1531:1542	a positive relationship	1520:1542	a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21)	1520:1593	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	34	dep	CI	1496:1497	arg1	to					1505:1506	to	1505:1506	to	1505:1506	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	0	35	theme	Bone	96:99	arg1	Density					109:115	Bone Mineral Density	96:115	Bone Mineral Density	96:115	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	2	36	theme	sclerostin	289:298	arg1	levels					279:284	circulating levels	267:284	circulating levels of sclerostin	267:298	Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR).
31170332	0	37	from	Influence	50:58	arg1	Fractures					121:129	Fractures	121:129	Fractures	121:129	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	0	37	from	Influence	50:58	arg1	Density					109:115	Bone Mineral Density	96:115	Bone Mineral Density	96:115	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	2	38	theme	Mendelian	390:398	arg1	MR					415:416	MR	415:416	MR	415:416	Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR).
31170332	2	38	theme	Mendelian	390:398	arg1	randomization					400:412	two-sample Mendelian randomization	379:412	two-sample Mendelian randomization (MR)	379:417	Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR).
31170332	6	39	theme	%	1576:1576	arg1	risk					1558:1561	fracture risk	1549:1561	fracture risk (β = 0.11, 95% CI 0.01 to 0.21)	1549:1593	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	39	theme	%	1576:1576	arg1	CI					1578:1579	β = 0.11, 95% CI 0.01 to 0.21	1564:1592	CI	1578:1579	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	8	40	theme	higher	1814:1819	arg1	levels					1832:1837	higher sclerostin levels	1814:1837	higher sclerostin levels	1814:1837	Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk.
31170332	0	41	theme	Mendelian	0:8	arg1	Randomization					10:22	Mendelian Randomization	0:22	Mendelian Randomization Analysis	0:31	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	4	42	from	GALNT1	960:965	arg1	sclerostin					903:912	sclerostin	903:912	sclerostin	903:912	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	6	43	with	relationship	1355:1366	arg1	risk					1558:1561	fracture risk	1549:1561	fracture risk (β = 0.11, 95% CI 0.01 to 0.21)	1549:1593	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	43	with	relationship	1355:1366	arg1	CI					1578:1579	β = 0.11, 95% CI 0.01 to 0.21	1564:1592	CI	1578:1579	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	7	44	from	sclerostin	1693:1702	arg1	%					1784:1784	probability >99%	1769:1784	probability >99%	1769:1784	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	7	44	from	sclerostin	1693:1702	arg1	tissue					1761:1766	arterial tissue	1752:1766	arterial tissue (probability >99%)	1752:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	5	45	dep	N-acetyl-galactosaminyltransferase	1025:1058	arg1	whereas					1175:1181	whereas	1175:1181	whereas	1175:1181	B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation.
31170332	6	46	theme	causal	1348:1353	arg1	relationship					1355:1366	an inverse causal relationship	1337:1366	an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10)	1337:1513	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	7	47	theme	arterial	1752:1759	arg1	%					1784:1784	probability >99%	1769:1784	probability >99%	1769:1784	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	7	47	theme	arterial	1752:1759	arg1	tissue					1761:1766	arterial tissue	1752:1766	arterial tissue (probability >99%)	1752:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	3	48	theme	bone	635:638	arg1	BMD					657:659	BMD; n = 32,744	657:671	BMD; n = 32,744	657:671	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	48	theme	bone	635:638	arg1	density					648:654	femoral neck bone mineral density	622:654	femoral neck bone mineral density (BMD; n = 32,744) in GEFOS	622:681	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	5	49	theme	LacdiNAc	1079:1086	arg1	disaccharide					1088:1099	a terminal LacdiNAc disaccharide	1068:1099	a terminal LacdiNAc disaccharide	1068:1099	B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation.
31170332	1	50	theme	adaptive	217:224	arg1	responses					226:234	adaptive responses	217:234	adaptive responses to mechanical loading	217:256	In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading.
31170332	6	51	dep	sclerostin	1382:1391	arg1	-0.05					1464:1468	-0.05	1464:1468	-0.05	1464:1468	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	7	52	theme	higher	1686:1691	arg1	sclerostin					1693:1702	higher sclerostin	1686:1702	higher sclerostin	1686:1702	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	4	53	dep	identified	814:823	arg1	= 0.11					970:975	β = 0.11	968:975	β = 0.11 per G allele	968:988	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	54	theme	β	968:968	arg1	= 0.11					970:975	β = 0.11	968:975	β = 0.11 per G allele	968:988	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	3	55	theme	association	495:505	arg1	meta-analysis					520:532	a genomewide association study (GWAS) meta-analysis	482:532	a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals	482:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	4	56	from	change	893:898	arg1	sclerostin					903:912	sclerostin	903:912	sclerostin	903:912	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	9	57	theme	glycosylation	1980:1992	arg1	enzymes					1994:2000	glycosylation enzymes	1980:2000	glycosylation enzymes	1980:2000	Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis.
31170332	6	58	theme	femoral	1397:1403	arg1	BMD					1410:1412	femoral neck BMD	1397:1412	femoral neck BMD	1397:1412	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	11	59	theme	Bone	2112:2115	arg1	Journal					2101:2107	Journal	2101:2107	Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.	2101:2173	Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
31170332	7	60	theme	common	1633:1638	arg1	signals					1648:1654	common genetic signals	1633:1654	common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%)	1633:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	3	61	theme	bone	697:700	arg1	eBMD					719:722	eBMD	719:722	eBMD	719:722	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	61	theme	bone	697:700	arg1	density					710:716	estimated bone mineral density	687:716	estimated bone mineral density (eBMD)	687:723	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	9	62	theme	GWAS	2022:2025	arg1	results					2027:2033	our GWAS results	2018:2033	our GWAS results	2018:2033	Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis.
31170332	3	63	theme	sclerostin	543:552	arg1	meta-analysis					520:532	a genomewide association study (GWAS) meta-analysis	482:532	a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals	482:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	1	64	theme	important	193:201	arg1	role					209:212	an important local role	190:212	an important local role	190:212	In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading.
31170332	3	65	theme	European-descent	564:579	arg1	individuals					581:591	10,584 European-descent individuals	557:591	10,584 European-descent individuals	557:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	4	66	theme	B4GALNT3	858:865	arg1	loci					852:855	two novel serum sclerostin loci	825:855	two novel serum sclerostin loci	825:855	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	66	theme	B4GALNT3	858:865	arg1	change					893:898	B4GALNT3 (standard deviation [SD]) change	858:898	B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 )	858:954	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	11	67	theme	Mineral	2121:2127	arg1	Research					2129:2136	Mineral Research	2121:2136	Mineral Research	2121:2136	Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
31170332	6	68	with	relationship	1531:1542	arg1	risk					1558:1561	fracture risk	1549:1561	fracture risk (β = 0.11, 95% CI 0.01 to 0.21)	1549:1593	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	68	with	relationship	1531:1542	arg1	CI					1578:1579	β = 0.11, 95% CI 0.01 to 0.21	1564:1592	CI	1578:1579	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	69	theme	single-nucleotide	1262:1278	arg1	SNPs					1295:1298	SNPs	1295:1298	SNPs	1295:1298	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	69	theme	single-nucleotide	1262:1278	arg1	polymorphisms					1280:1292	these two single-nucleotide polymorphisms	1252:1292	these two single-nucleotide polymorphisms (SNPs)	1252:1299	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	69	theme	single-nucleotide	1262:1278	arg1	instruments					1312:1322	genetic instruments	1304:1322	genetic instruments	1304:1322	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	70	theme	confidence	1430:1439	arg1	[CI					1450:1452	β = -0.12, 95% confidence interval [CI	1415:1452	β = -0.12, 95% confidence interval [CI	1415:1452	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	70	theme	confidence	1430:1439	arg1	sclerostin					1382:1391	serum sclerostin	1376:1391	serum sclerostin	1376:1391	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	4	71	theme	standard	868:875	arg1	B4GALNT3					858:865	B4GALNT3	858:865	B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 )	858:954	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	71	theme	standard	868:875	arg1	deviation					877:885	standard deviation [SD]	868:890	standard deviation [SD]	868:890	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	6	72	theme	genetic	1304:1310	arg1	polymorphisms					1280:1292	these two single-nucleotide polymorphisms	1252:1292	these two single-nucleotide polymorphisms (SNPs)	1252:1299	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	72	theme	genetic	1304:1310	arg1	instruments					1312:1322	genetic instruments	1304:1322	genetic instruments	1304:1322	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	73	theme	%	1494:1494	arg1	eBMD					1475:1478	eBMD	1475:1478	eBMD (β = -0.12, 95% CI -0.14 to -0.10)	1475:1513	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	73	theme	%	1494:1494	arg1	CI					1496:1497	β = -0.12, 95% CI -0.14 to -0.10	1481:1512	CI	1496:1497	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	4	74	theme	serum	835:839	arg1	loci					852:855	two novel serum sclerostin loci	825:855	two novel serum sclerostin loci	825:855	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	74	theme	serum	835:839	arg1	change					893:898	B4GALNT3 (standard deviation [SD]) change	858:898	B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 )	858:954	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	4	74	theme	serum	835:839	arg1	GALNT1					960:965	GALNT1	960:965	GALNT1	960:965	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	2	75	theme	circulating	267:277	arg1	levels					279:284	circulating levels	267:284	circulating levels of sclerostin	267:298	Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR).
31170332	7	76	theme	Colocalization	1596:1609	arg1	analysis					1611:1618	Colocalization analysis	1596:1618	Colocalization analysis	1596:1618	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	6	77	dep	CI	1578:1579	arg1	to					1586:1587	to	1586:1587	to	1586:1587	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	5	78	theme	mucin-type	1211:1220	arg1	glycosylation					1231:1243	mucin-type O-linked glycosylation	1211:1243	mucin-type O-linked glycosylation	1211:1243	B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation.
31170332	0	79	theme	Sclerostin	75:84	arg1	Levels					86:91	Circulating Sclerostin Levels	63:91	Circulating Sclerostin Levels	63:91	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	10	80	dep	Authors	2092:2098	arg1	2019					2083:2086	© 2019	2081:2086	© 2019	2081:2086	© 2019 The Authors.
31170332	7	81	theme	greater	1721:1727	arg1	expression					1738:1747	greater B4GALNT3 expression	1721:1747	greater B4GALNT3 expression in arterial tissue (probability >99%)	1721:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	3	82	from	ultrasound	733:742	arg1	Biobank					796:802	Biobank	796:802	Biobank	796:802	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	10	83	theme	©	2081:2081	arg1	2019					2083:2086	© 2019	2081:2086	© 2019	2081:2086	© 2019 The Authors.
31170332	0	84	theme	Mineral	101:107	arg1	Density					109:115	Bone Mineral Density	96:115	Bone Mineral Density	96:115	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	4	85	dep	= 0.11	970:975	arg1	p = 4.4 × 10-11					991:1005	p = 4.4 × 10-11	991:1005	p = 4.4 × 10-11	991:1005	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	2	86	theme	two-sample	379:388	arg1	MR					415:416	MR	415:416	MR	415:416	Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR).
31170332	2	86	theme	two-sample	379:388	arg1	randomization					400:412	two-sample Mendelian randomization	379:412	two-sample Mendelian randomization (MR)	379:417	Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two-sample Mendelian randomization (MR).
31170332	0	87	theme	Randomization	10:22	arg1	Analysis					24:31	Mendelian Randomization Analysis	0:31	Mendelian Randomization Analysis	0:31	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	7	88	theme	probability	1769:1779	arg1	%					1784:1784	probability >99%	1769:1784	probability >99%	1769:1784	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	7	88	theme	probability	1769:1779	arg1	tissue					1761:1766	arterial tissue	1752:1766	arterial tissue (probability >99%)	1752:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	1	89	from	bone	135:138	arg1	osteocyte-derived					162:178	osteocyte-derived	162:178	osteocyte-derived	162:178	In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading.
31170332	6	90	theme	serum	1376:1380	arg1	[CI					1450:1452	β = -0.12, 95% confidence interval [CI	1415:1452	β = -0.12, 95% confidence interval [CI	1415:1452	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	90	theme	serum	1376:1380	arg1	sclerostin					1382:1391	serum sclerostin	1376:1391	serum sclerostin	1376:1391	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	5	91	theme	target	1104:1109	arg1	glycocoproteins					1111:1125	target glycocoproteins	1104:1125	target glycocoproteins	1104:1125	B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation.
31170332	3	92	theme	mineral	640:646	arg1	BMD					657:659	BMD; n = 32,744	657:671	BMD; n = 32,744	657:671	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	92	theme	mineral	640:646	arg1	density					648:654	femoral neck bone mineral density	622:654	femoral neck bone mineral density (BMD; n = 32,744) in GEFOS	622:681	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	0	93	theme	Causal	43:48	arg1	Influence					50:58	a Causal Influence	41:58	a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures	41:129	Mendelian Randomization Analysis Reveals a Causal Influence of Circulating Sclerostin Levels on Bone Mineral Density and Fractures.
31170332	7	94	from	eBMD	1711:1714	arg1	%					1784:1784	probability >99%	1769:1784	probability >99%	1769:1784	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	7	94	from	eBMD	1711:1714	arg1	tissue					1761:1766	arterial tissue	1752:1766	arterial tissue (probability >99%)	1752:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	3	95	theme	genetic	422:428	arg1	instrument					430:439	A genetic instrument	420:439	A genetic instrument	420:439	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	96	theme	neck	630:633	arg1	BMD					657:659	BMD; n = 32,744	657:671	BMD; n = 32,744	657:671	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	96	theme	neck	630:633	arg1	density					648:654	femoral neck bone mineral density	622:654	femoral neck bone mineral density (BMD; n = 32,744) in GEFOS	622:681	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	97	theme	circulating	445:455	arg1	sclerostin					457:466	circulating sclerostin	445:466	circulating sclerostin	445:466	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	6	98	theme	inverse	1340:1346	arg1	relationship					1355:1366	an inverse causal relationship	1337:1366	an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10)	1337:1513	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	5	99	theme	terminal	1070:1077	arg1	disaccharide					1088:1099	a terminal LacdiNAc disaccharide	1068:1099	a terminal LacdiNAc disaccharide	1068:1099	B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation.
31170332	7	100	theme	B4GALNT3	1729:1736	arg1	expression					1738:1747	greater B4GALNT3 expression	1721:1747	greater B4GALNT3 expression in arterial tissue (probability >99%)	1721:1785	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	9	101	theme	circulating	1931:1941	arg1	sclerostin					1943:1952	circulating sclerostin	1931:1952	circulating sclerostin	1931:1952	Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis.
31170332	3	102	theme	genomewide	484:493	arg1	meta-analysis					520:532	a genomewide association study (GWAS) meta-analysis	482:532	a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals	482:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	6	103	theme	%	1428:1428	arg1	[CI					1450:1452	β = -0.12, 95% confidence interval [CI	1415:1452	β = -0.12, 95% confidence interval [CI	1415:1452	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	6	103	theme	%	1428:1428	arg1	sclerostin					1382:1391	serum sclerostin	1376:1391	serum sclerostin	1376:1391	Using these two single-nucleotide polymorphisms (SNPs) as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β = -0.12, 95% confidence interval [CI] -0.20 to -0.05) and eBMD (β = -0.12, 95% CI -0.14 to -0.10), and a positive relationship with fracture risk (β = 0.11, 95% CI 0.01 to 0.21).
31170332	7	104	theme	lower	1705:1709	arg1	eBMD					1711:1714	lower eBMD	1705:1714	lower eBMD	1705:1714	Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (probability >99%).
31170332	4	105	theme	G	981:981	arg1	allele					983:988	G allele	981:988	G allele	981:988	Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation [SD]) change in sclerostin per A allele (β = 0.20, p = 4.6 × 10-49 ) and GALNT1 (β = 0.11 per G allele, p = 4.4 × 10-11 ).
31170332	3	106	from	risk	771:774	arg1	Biobank					796:802	Biobank	796:802	Biobank	796:802	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	3	107	theme	GWAS	514:517	arg1	meta-analysis					520:532	a genomewide association study (GWAS) meta-analysis	482:532	a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals	482:591	A genetic instrument for circulating sclerostin, derived from a genomewide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n = 32,744) in GEFOS and estimated bone mineral density (eBMD) by heel ultrasound (n = 426,824) and fracture risk (n = 426,795) in UK Biobank.
31170332	1	108	theme	mechanical	239:248	arg1	loading					250:256	mechanical loading	239:256	mechanical loading	239:256	In bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading.
30718403	0	0	from	diversity	13:21	arg1	chimpanzees					26:36	chimpanzees	26:36	chimpanzees	26:36	CD4 receptor diversity in chimpanzees protects against SIV infection.
30718403	1	1	theme	primary	138:144	arg1	CD4					127:129	CD4	127:129	CD4	127:129	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	1	1	theme	primary	138:144	arg1	receptor					146:153	the primary receptor	134:153	the primary receptor	134:153	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	8	2	from	diversity	1293:1301	arg1	all					1306:1308	all	1306:1308	all	1306:1308	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	8	2	from	diversity	1293:1301	arg1	subspecies					1326:1335	the western subspecies	1314:1335	the western subspecies	1314:1335	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	8	3	theme	CD4	1229:1231	arg1	frequencies					1240:1250	CD4 allele frequencies	1229:1250	CD4 allele frequencies	1229:1250	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	5	4	theme	N-linked	819:826	arg1	N66					848:850	N66	848:850	N66	848:850	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	4	theme	N-linked	819:826	arg1	site					842:845	a second N-linked glycosylation site	810:845	a second N-linked glycosylation site (N66)	810:851	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	5	theme	glycosylation	828:840	arg1	N66					848:850	N66	848:850	N66	848:850	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	5	theme	glycosylation	828:840	arg1	site					842:845	a second N-linked glycosylation site	810:845	a second N-linked glycosylation site (N66)	810:851	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	7	6	theme	Env-mediated	1135:1146	arg1	entry					1153:1157	Env-mediated cell entry	1135:1157	Env-mediated cell entry	1135:1157	CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan.
30718403	9	7	theme	SIVcpz	1427:1432	arg1	rates					1445:1449	lower SIVcpz prevalence rates	1421:1449	lower SIVcpz prevalence rates in the wild	1421:1461	One allele was associated with lower SIVcpz prevalence rates in the wild.
30718403	2	8	from	populations	281:291	arg1	present					265:271	present	265:271	present	265:271	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	2	9	theme	coding	249:254	arg1	variants					256:263	nine coding variants	244:263	nine coding variants present in wild populations	244:291	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	6	10	theme	site-directed	947:959	arg1	mutagenesis					961:971	site-directed mutagenesis	947:971	site-directed mutagenesis	947:971	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	5	11	theme	invariant	871:879	arg1	N32					881:883	an invariant N32	868:883	an invariant N32 encoded by all chimpanzee CD4 alleles	868:921	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	2	12	theme	wild	276:279	arg1	populations					281:291	wild populations	276:291	wild populations	276:291	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	6	13	dep	In	924:925	arg1	silico					927:932	silico	927:932	silico	927:932	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	3	14	theme	captive	442:448	arg1	chimpanzees					450:460	captive chimpanzees	442:460	captive chimpanzees	442:460	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	5	15	dep	N32	881:883	arg1	addition					856:863	addition	856:863	addition	856:863	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	1	16	theme	Human	70:74	arg1	HIV/SIVs					113:120	HIV/SIVs	113:120	HIV/SIVs	113:120	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	1	16	theme	Human	70:74	arg1	viruses					104:110	Human and simian immunodeficiency viruses	70:110	Human and simian immunodeficiency viruses (HIV/SIVs)	70:121	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	3	17	theme	replication	383:393	arg1	fitness					395:401	the replication fitness	379:401	the replication fitness of SIVcpz strains	379:419	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	5	18	dep	substitutions	751:763	arg1	P68T					782:785	P68T	782:785	P68T	782:785	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	18	dep	substitutions	751:763	arg1	Q25R					766:769	Q25R	766:769	Q25R	766:769	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	18	dep	substitutions	751:763	arg1	substitutions					751:763	three substitutions	745:763	three substitutions (Q25R, Q40R, and P68T)	745:786	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	18	dep	substitutions	751:763	arg1	Q40R					772:775	Q40R	772:775	Q40R	772:775	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	11	19	theme	SIVcpz	1587:1592	arg1	strains					1594:1600	some SIVcpz strains	1582:1600	some SIVcpz strains	1582:1600	Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.
30718403	6	20	theme	inhibition	1092:1101	arg1	mechanisms					1078:1087	mechanisms	1078:1087	mechanisms of inhibition	1078:1101	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	6	20	theme	inhibition	1092:1101	arg1	residues					992:999	charged residues	984:999	charged residues at the CD4-Env interface	984:1024	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	6	20	theme	inhibition	1092:1101	arg1	clashes					1030:1036	clashes	1030:1036	clashes between CD4- and Env-encoded glycans	1030:1073	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	10	21	theme	CD4	1541:1543	arg1	CD4					1541:1543	the chimpanzee CD4	1526:1543	the chimpanzee CD4	1526:1543	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	10	21	theme	CD4	1541:1543	arg1	domain					1516:1521	the D1 domain	1509:1521	the D1 domain of the chimpanzee CD4	1509:1543	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	0	22	theme	receptor	4:11	arg1	diversity					13:21	CD4 receptor diversity	0:21	CD4 receptor diversity in chimpanzees	0:36	CD4 receptor diversity in chimpanzees protects against SIV infection.
30718403	7	23	theme	D1	1211:1212	arg1	glycan					1221:1226	at least one D1 domain glycan	1198:1226	at least one D1 domain glycan	1198:1226	CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan.
30718403	1	24	theme	simian	80:85	arg1	HIV/SIVs					113:120	HIV/SIVs	113:120	HIV/SIVs	113:120	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	1	24	theme	simian	80:85	arg1	viruses					104:110	Human and simian immunodeficiency viruses	70:110	Human and simian immunodeficiency viruses (HIV/SIVs)	70:121	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	7	25	theme	CD4	1104:1106	arg1	polymorphisms					1108:1120	CD4 polymorphisms	1104:1120	CD4 polymorphisms	1104:1120	CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan.
30718403	1	26	theme	target	164:169	arg1	cells					171:175	target cells	164:175	target cells	164:175	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	0	27	theme	CD4	0:2	arg1	diversity					13:21	CD4 receptor diversity	0:21	CD4 receptor diversity in chimpanzees	0:36	CD4 receptor diversity in chimpanzees protects against SIV infection.
30718403	11	28	with	infection	1702:1710	arg1	SIVcpz					1717:1722	SIVcpz	1717:1722	SIVcpz	1717:1722	Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.
30718403	11	28	with	infection	1702:1710	arg1	SIVs					1734:1737	other SIVs	1728:1737	other SIVs	1728:1737	Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.
30718403	1	29	theme	immunodeficiency	87:102	arg1	HIV/SIVs					113:120	HIV/SIVs	113:120	HIV/SIVs	113:120	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	1	29	theme	immunodeficiency	87:102	arg1	viruses					104:110	Human and simian immunodeficiency viruses	70:110	Human and simian immunodeficiency viruses (HIV/SIVs)	70:121	Human and simian immunodeficiency viruses (HIV/SIVs) use CD4 as the primary receptor to enter target cells.
30718403	6	30	theme	charged	984:990	arg1	mechanisms					1078:1087	mechanisms	1078:1087	mechanisms of inhibition	1078:1101	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	6	30	theme	charged	984:990	arg1	residues					992:999	charged residues	984:999	charged residues at the CD4-Env interface	984:1024	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	6	30	theme	charged	984:990	arg1	clashes					1030:1036	clashes	1030:1036	clashes between CD4- and Env-encoded glycans	1030:1073	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	9	31	from	rates	1445:1449	arg1	wild					1458:1461	wild	1458:1461	wild	1458:1461	One allele was associated with lower SIVcpz prevalence rates in the wild.
30718403	5	32	link	N-linked	819:826	arg1	N66					848:850	N66	848:850	N66	848:850	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	32	link	N-linked	819:826	arg1	site					842:845	a second N-linked glycosylation site	810:845	a second N-linked glycosylation site (N66)	810:851	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	2	33	theme	present	265:271	arg1	variants					256:263	nine coding variants	244:263	nine coding variants present in wild populations	244:291	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	3	34	theme	certain	526:532	arg1	hosts					534:538	certain hosts	526:538	certain hosts	526:538	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	3	35	theme	strains	413:419	arg1	fitness					395:401	the replication fitness	379:401	the replication fitness of SIVcpz strains	379:419	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	4	36	theme	infection	675:683	arg1	phenotypes					685:694	SIVcpz infection phenotypes	668:694	SIVcpz infection phenotypes	668:694	These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes.
30718403	10	37	from	substitutions	1492:1504	arg1	CD4					1541:1543	the chimpanzee CD4	1526:1543	the chimpanzee CD4	1526:1543	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	10	37	from	substitutions	1492:1504	arg1	domain					1516:1521	the D1 domain	1509:1521	the D1 domain of the chimpanzee CD4	1509:1543	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	6	38	theme	CD4-Env	1008:1014	arg1	interface					1016:1024	the CD4-Env interface	1004:1024	the CD4-Env interface	1004:1024	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	8	39	theme	high	1288:1291	arg1	diversity					1293:1301	high diversity	1288:1301	high diversity in all but the western subspecies, which appeared to have undergone a selective sweep	1288:1387	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	8	40	theme	allele	1233:1238	arg1	frequencies					1240:1250	CD4 allele frequencies	1229:1250	CD4 allele frequencies	1229:1250	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	7	41	theme	domain	1214:1219	arg1	glycan					1221:1226	at least one D1 domain glycan	1198:1226	at least one D1 domain glycan	1198:1226	CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan.
30718403	2	42	attach	present	265:271	arg1	populations					281:291	wild populations	276:291	wild populations	276:291	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	2	42	attach	present	265:271	arg2	variants					256:263	nine coding variants	244:263	nine coding variants present in wild populations	244:291	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	4	43	theme	transfection	585:596	arg1	assays					598:603	CD4 transfection assays	581:603	CD4 transfection assays	581:603	These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes.
30718403	2	44	theme	chimpanzee	201:210	arg1	CD4					212:214	the chimpanzee CD4	197:214	the chimpanzee CD4	197:214	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	2	44	theme	chimpanzee	201:210	arg1	polymorphic					226:236	polymorphic	226:236	polymorphic	226:236	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	3	45	from	hosts	534:538	arg1	cells					515:519	cells	515:519	cells from certain hosts	515:538	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	2	46	theme	-CD4	352:355	arg1	interactions					357:368	SIV envelope (Env)-CD4 interactions	334:368	SIV envelope (Env)-CD4 interactions	334:368	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	10	47	theme	SIV	1557:1559	arg1	entry					1566:1570	SIV cell entry	1557:1570	SIV cell entry	1557:1570	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	11	48	theme	other	1728:1732	arg1	SIVs					1734:1737	other SIVs	1728:1737	other SIVs	1728:1737	Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.
30718403	3	49	theme	SIVcpz	406:411	arg1	strains					413:419	SIVcpz strains	406:419	SIVcpz strains	406:419	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	0	50	theme	SIV	55:57	arg1	infection					59:67	SIV infection	55:67	SIV infection	55:67	CD4 receptor diversity in chimpanzees protects against SIV infection.
30718403	9	51	theme	prevalence	1434:1443	arg1	rates					1445:1449	lower SIVcpz prevalence rates	1421:1449	lower SIVcpz prevalence rates in the wild	1421:1461	One allele was associated with lower SIVcpz prevalence rates in the wild.
30718403	8	52	theme	wild	1265:1268	arg1	chimpanzees					1270:1280	wild chimpanzees	1265:1280	wild chimpanzees	1265:1280	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	7	53	theme	SIVs	1169:1172	arg1	entry					1153:1157	Env-mediated cell entry	1135:1157	Env-mediated cell entry	1135:1157	CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan.
30718403	8	54	theme	western	1318:1324	arg1	subspecies					1326:1335	the western subspecies	1314:1335	the western subspecies	1314:1335	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	6	55	theme	CD4-	1046:1049	arg1	glycans					1067:1073	CD4- and Env-encoded glycans	1046:1073	CD4- and Env-encoded glycans	1046:1073	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	6	56	theme	Env-encoded	1055:1065	arg1	glycans					1067:1073	CD4- and Env-encoded glycans	1046:1073	CD4- and Env-encoded glycans	1046:1073	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	10	57	theme	cell	1561:1564	arg1	entry					1566:1570	SIV cell entry	1557:1570	SIV cell entry	1557:1570	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	2	58	with	polymorphic	226:236	arg1	variants					256:263	nine coding variants	244:263	nine coding variants present in wild populations	244:291	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	4	59	theme	CD4	650:652	arg1	genotypes					654:662	CD4 genotypes	650:662	CD4 genotypes	650:662	These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes.
30718403	10	60	theme	chimpanzee	1530:1539	arg1	CD4					1541:1543	the chimpanzee CD4	1526:1543	the chimpanzee CD4	1526:1543	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	5	61	gly	glycosylation	828:840	arg2	N66					848:850	N66	848:850	N66	848:850	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	61	gly	glycosylation	828:840	arg2	site					842:845	a second N-linked glycosylation site	810:845	a second N-linked glycosylation site (N66)	810:851	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	8	62	theme	selective	1373:1381	arg1	sweep					1383:1387	a selective sweep	1371:1387	a selective sweep	1371:1387	CD4 allele frequencies varied among wild chimpanzees, with high diversity in all but the western subspecies, which appeared to have undergone a selective sweep.
30718403	3	63	from	chimpanzees	450:460	arg1	cells					431:435	CD4+ T cells	424:435	CD4+ T cells from captive chimpanzees	424:460	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	3	64	theme	CD4+	424:427	arg1	cells					431:435	CD4+ T cells	424:435	CD4+ T cells from captive chimpanzees	424:460	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	11	65	theme	CD4	1642:1644	arg1	diversity					1646:1654	CD4 diversity	1642:1654	CD4 diversity	1642:1654	Although some SIVcpz strains have adapted to utilize these variants, CD4 diversity is maintained, protecting chimpanzees against infection with SIVcpz and other SIVs to which they are exposed.
30718403	3	66	theme	certain	477:483	arg1	viruses					485:491	certain viruses	477:491	certain viruses	477:491	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	6	67	from	interface	1016:1024	arg1	mechanisms					1078:1087	mechanisms	1078:1087	mechanisms of inhibition	1078:1101	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	6	67	from	interface	1016:1024	arg1	residues					992:999	charged residues	984:999	charged residues at the CD4-Env interface	984:1024	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	6	67	from	interface	1016:1024	arg1	clashes					1030:1036	clashes	1030:1036	clashes between CD4- and Env-encoded glycans	1030:1073	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	3	68	theme	T	429:429	arg1	cells					431:435	CD4+ T cells	424:435	CD4+ T cells from captive chimpanzees	424:460	Testing the replication fitness of SIVcpz strains in CD4+ T cells from captive chimpanzees, we found that certain viruses were unable to infect cells from certain hosts.
30718403	4	69	theme	SIVcpz	668:673	arg1	phenotypes					685:694	SIVcpz infection phenotypes	668:694	SIVcpz infection phenotypes	668:694	These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes.
30718403	7	70	theme	monkey	1162:1167	arg1	SIVs					1169:1172	monkey SIVs	1162:1172	monkey SIVs	1162:1172	CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan.
30718403	4	71	theme	CD4	581:583	arg1	assays					598:603	CD4 transfection assays	581:603	CD4 transfection assays	581:603	These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes.
30718403	5	72	theme	CD4	911:913	arg1	alleles					915:921	all chimpanzee CD4 alleles	896:921	all chimpanzee CD4 alleles	896:921	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	9	73	theme	lower	1421:1425	arg1	rates					1445:1449	lower SIVcpz prevalence rates	1421:1449	lower SIVcpz prevalence rates in the wild	1421:1461	One allele was associated with lower SIVcpz prevalence rates in the wild.
30718403	4	74	theme	strong	623:628	arg1	association					630:640	a strong association	621:640	a strong association between CD4 genotypes and SIVcpz infection phenotypes	621:694	These differences were recapitulated in CD4 transfection assays, which revealed a strong association between CD4 genotypes and SIVcpz infection phenotypes.
30718403	6	75	theme	In	924:925	arg1	modeling					934:941	In silico modeling	924:941	In silico modeling	924:941	In silico modeling and site-directed mutagenesis identified charged residues at the CD4-Env interface and clashes between CD4- and Env-encoded glycans as mechanisms of inhibition.
30718403	5	76	theme	striking	706:713	arg1	differences					715:725	The most striking differences	697:725	The most striking differences	697:725	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	10	77	theme	D1	1513:1514	arg1	CD4					1541:1543	the chimpanzee CD4	1526:1543	the chimpanzee CD4	1526:1543	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	10	77	theme	D1	1513:1514	arg1	domain					1516:1521	the D1 domain	1509:1521	the D1 domain of the chimpanzee CD4	1509:1543	These results indicate that substitutions in the D1 domain of the chimpanzee CD4 can prevent SIV cell entry.
30718403	5	78	theme	second	812:817	arg1	N66					848:850	N66	848:850	N66	848:850	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	5	78	theme	second	812:817	arg1	site					842:845	a second N-linked glycosylation site	810:845	a second N-linked glycosylation site (N66)	810:851	The most striking differences were observed for three substitutions (Q25R, Q40R, and P68T), with P68T generating a second N-linked glycosylation site (N66) in addition to an invariant N32 encoded by all chimpanzee CD4 alleles.
30718403	2	79	from	present	265:271	arg1	populations					281:291	wild populations	276:291	wild populations	276:291	Here, we show that the chimpanzee CD4 is highly polymorphic, with nine coding variants present in wild populations, and that this diversity interferes with SIV envelope (Env)-CD4 interactions.
30718403	7	80	theme	cell	1148:1151	arg1	entry					1153:1157	Env-mediated cell entry	1135:1157	Env-mediated cell entry	1135:1157	CD4 polymorphisms also reduced Env-mediated cell entry of monkey SIVs, which was dependent on at least one D1 domain glycan.
34495528	5	0	theme	amino	687:691	arg1	acid					693:696	any amino acid	683:696	any amino acid	683:696	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	6	1	theme	N-glycosylated	753:766	arg1	proteins					776:783	the N-glycosylated nascent proteins	749:783	the N-glycosylated nascent proteins	749:783	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	10	2	from	overview	1506:1513	arg1	Golgi					1570:1574	Golgi	1570:1574	Golgi	1570:1574	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	10	2	from	overview	1506:1513	arg1	ER					1563:1564	ER	1563:1564	ER	1563:1564	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	7	3	from	proteasomes	1110:1120	arg1	cytosol					1129:1135	the cytosol	1125:1135	the cytosol	1125:1135	Despite the N-glycan-dependent folding process, some glycoproteins do not fold correctly, and these misfolded glycoproteins are destined to degradation by proteasomes in the cytosol.
34495528	3	4	theme	pathological	334:345	arg1	processes					347:355	numerous physiological and pathological processes	307:355	numerous physiological and pathological processes	307:355	Thus, glycan modification to proteins is profoundly involved in numerous physiological and pathological processes.
34495528	4	5	theme	sugar	554:558	arg1	residues					560:567	14 sugar residues	551:567	14 sugar residues	551:567	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	10	6	theme	N-glycans	1546:1554	arg1	pathway					1535:1541	the biosynthetic pathway	1518:1541	the biosynthetic pathway of N-glycans in the ER and Golgi	1518:1574	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	4	7	theme	enzymatic	471:479	arg1	reactions					481:489	sequential enzymatic reactions	460:489	sequential enzymatic reactions	460:489	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	5	8	theme	consensus	642:650	arg1	N-X-S/T					661:667	the consensus sequence N-X-S/T	638:667	the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins	638:732	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	7	9	theme	N-glycan-dependent	967:984	arg1	process					994:1000	the N-glycan-dependent folding process	963:1000	the N-glycan-dependent folding process	963:1000	Despite the N-glycan-dependent folding process, some glycoproteins do not fold correctly, and these misfolded glycoproteins are destined to degradation by proteasomes in the cytosol.
34495528	7	10	gly	glycoproteins	1008:1020	arg1	glycoproteins					1008:1020	some glycoproteins	1003:1020	some glycoproteins	1003:1020	Despite the N-glycan-dependent folding process, some glycoproteins do not fold correctly, and these misfolded glycoproteins are destined to degradation by proteasomes in the cytosol.
34495528	2	11	theme	biological	159:168	arg1	transduction					229:240	signal transduction	222:240	signal transduction	222:240	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	11	theme	biological	159:168	arg1	functions					170:178	many biological functions	154:178	many biological functions such as protein folding, trafficking, and signal transduction	154:240	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	11	theme	biological	159:168	arg1	trafficking					205:215	trafficking	205:215	trafficking	205:215	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	11	theme	biological	159:168	arg1	folding					196:202	protein folding	188:202	protein folding	188:202	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	5	12	theme	sequence	652:659	arg1	N-X-S/T					661:667	the consensus sequence N-X-S/T	638:667	the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins	638:732	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	2	13	theme	many	154:157	arg1	transduction					229:240	signal transduction	222:240	signal transduction	222:240	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	13	theme	many	154:157	arg1	functions					170:178	many biological functions	154:178	many biological functions such as protein folding, trafficking, and signal transduction	154:240	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	13	theme	many	154:157	arg1	trafficking					205:215	trafficking	205:215	trafficking	205:215	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	13	theme	many	154:157	arg1	folding					196:202	protein folding	188:202	protein folding	188:202	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	3	14	theme	glycan	249:254	arg1	modification					256:267	glycan modification	249:267	glycan modification to proteins	249:279	Thus, glycan modification to proteins is profoundly involved in numerous physiological and pathological processes.
34495528	10	15	theme	biosynthetic	1522:1533	arg1	pathway					1535:1541	the biosynthetic pathway	1518:1541	the biosynthetic pathway of N-glycans in the ER and Golgi	1518:1574	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	9	16	theme	N-glycan	1410:1417	arg1	structures					1419:1428	branched N-glycan structures	1401:1428	branched N-glycan structures	1401:1428	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V) produce branched N-glycan structures, affording a higher complexity to N-glycans.
34495528	1	17	from	humans	126:131	arg1	N-glycosylated					108:121	N-glycosylated	108:121	N-glycosylated	108:121	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	10	18	from	ER	1563:1564	arg1	overview					1506:1513	an overview	1503:1513	an overview of the biosynthetic pathway of N-glycans in the ER and Golgi	1503:1574	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	8	19	theme	complex-type	1307:1318	arg1	N-glycans					1320:1328	complex-type N-glycans	1307:1328	complex-type N-glycans	1307:1328	Properly folded proteins are transported to the Golgi, and N-glycans undergo maturation by the sequential reactions of glycosidases and glycosyltransferases, generating complex-type N-glycans.
34495528	4	20	theme	dolichol-linked	507:521	arg1	Glc3Man9GlcNAc2					570:584	Glc3Man9GlcNAc2	570:584	Glc3Man9GlcNAc2	570:584	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	4	20	theme	dolichol-linked	507:521	arg1	oligosaccharide					523:537	the dolichol-linked oligosaccharide	503:537	the dolichol-linked oligosaccharide composed of 14 sugar residues	503:567	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	10	21	theme	pathway	1535:1541	arg1	overview					1506:1513	an overview	1503:1513	an overview of the biosynthetic pathway of N-glycans in the ER and Golgi	1503:1574	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	4	22	from	phosphate	447:455	arg1	ER					429:430	ER	429:430	ER	429:430	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	4	22	from	phosphate	447:455	arg1	reticulum					418:426	the endoplasmic reticulum	402:426	the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2	402:584	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	8	23	theme	sequential	1233:1242	arg1	reactions					1244:1252	the sequential reactions	1229:1252	the sequential reactions of glycosidases and glycosyltransferases	1229:1293	Properly folded proteins are transported to the Golgi, and N-glycans undergo maturation by the sequential reactions of glycosidases and glycosyltransferases, generating complex-type N-glycans.
34495528	1	24	from	N-glycosylated	108:121	arg1	humans					126:131	humans	126:131	humans	126:131	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	6	25	theme	lectin-like	903:913	arg1	calnexin					927:934	calnexin	927:934	calnexin	927:934	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	6	25	theme	lectin-like	903:913	arg1	calreticulin					941:952	calreticulin	941:952	calreticulin	941:952	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	6	25	theme	lectin-like	903:913	arg1	chaperones					915:924	the lectin-like chaperones	899:924	the lectin-like chaperones	899:924	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	8	26	theme	glycosidases	1257:1268	arg1	reactions					1244:1252	the sequential reactions	1229:1252	the sequential reactions of glycosidases and glycosyltransferases	1229:1293	Properly folded proteins are transported to the Golgi, and N-glycans undergo maturation by the sequential reactions of glycosidases and glycosyltransferases, generating complex-type N-glycans.
34495528	4	27	theme	endoplasmic	406:416	arg1	ER					429:430	ER	429:430	ER	429:430	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	4	27	theme	endoplasmic	406:416	arg1	reticulum					418:426	the endoplasmic reticulum	402:426	the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2	402:584	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	7	28	theme	folding	986:992	arg1	process					994:1000	the N-glycan-dependent folding process	963:1000	the N-glycan-dependent folding process	963:1000	Despite the N-glycan-dependent folding process, some glycoproteins do not fold correctly, and these misfolded glycoproteins are destined to degradation by proteasomes in the cytosol.
34495528	10	29	from	pathway	1535:1541	arg1	Golgi					1570:1574	Golgi	1570:1574	Golgi	1570:1574	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	10	29	from	pathway	1535:1541	arg1	ER					1563:1564	ER	1563:1564	ER	1563:1564	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	1	30	gly	N-glycosylated	108:121	arg1	humans					126:131	humans	126:131	humans	126:131	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	1	30	gly	N-glycosylated	108:121	arg2	proteins					95:102	more than 7000 proteins	80:102	more than 7000 proteins	80:102	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	1	30	gly	N-glycosylated	108:121	arg1	proteins					95:102	more than 7000 proteins	80:102	more than 7000 proteins	80:102	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	2	31	theme	protein	188:194	arg1	folding					196:202	protein folding	188:202	protein folding	188:202	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	10	32	from	Golgi	1570:1574	arg1	overview					1506:1513	an overview	1503:1513	an overview of the biosynthetic pathway of N-glycans in the ER and Golgi	1503:1574	In this chapter, we provide an overview of the biosynthetic pathway of N-glycans in the ER and Golgi.
34495528	8	33	theme	glycosyltransferases	1274:1293	arg1	reactions					1244:1252	the sequential reactions	1229:1252	the sequential reactions of glycosidases and glycosyltransferases	1229:1293	Properly folded proteins are transported to the Golgi, and N-glycans undergo maturation by the sequential reactions of glycosidases and glycosyltransferases, generating complex-type N-glycans.
34495528	9	34	theme	higher	1443:1448	arg1	complexity					1450:1459	a higher complexity	1441:1459	a higher complexity to N-glycans	1441:1472	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V) produce branched N-glycan structures, affording a higher complexity to N-glycans.
34495528	9	35	theme	branched	1401:1408	arg1	structures					1419:1428	branched N-glycan structures	1401:1428	branched N-glycan structures	1401:1428	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V) produce branched N-glycan structures, affording a higher complexity to N-glycans.
34495528	4	36	theme	sequential	460:469	arg1	reactions					481:489	sequential enzymatic reactions	460:489	sequential enzymatic reactions	460:489	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	8	37	theme	folded	1147:1152	arg1	proteins					1154:1161	Properly folded proteins	1138:1161	Properly folded proteins	1138:1161	Properly folded proteins are transported to the Golgi, and N-glycans undergo maturation by the sequential reactions of glycosidases and glycosyltransferases, generating complex-type N-glycans.
34495528	4	38	theme	N-glycan	362:369	arg1	precursor					371:379	The N-glycan precursor	358:379	The N-glycan precursor	358:379	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	4	39	link	dolichol-linked	507:521	arg1	Glc3Man9GlcNAc2					570:584	Glc3Man9GlcNAc2	570:584	Glc3Man9GlcNAc2	570:584	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	4	39	link	dolichol-linked	507:521	arg1	oligosaccharide					523:537	the dolichol-linked oligosaccharide	503:537	the dolichol-linked oligosaccharide composed of 14 sugar residues	503:567	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	3	40	theme	numerous	307:314	arg1	processes					347:355	numerous physiological and pathological processes	307:355	numerous physiological and pathological processes	307:355	Thus, glycan modification to proteins is profoundly involved in numerous physiological and pathological processes.
34495528	2	41	theme	signal	222:227	arg1	transduction					229:240	signal transduction	222:240	signal transduction	222:240	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	3	42	theme	physiological	316:328	arg1	processes					347:355	numerous physiological and pathological processes	307:355	numerous physiological and pathological processes	307:355	Thus, glycan modification to proteins is profoundly involved in numerous physiological and pathological processes.
34495528	4	43	theme	dolichol	438:445	arg1	phosphate					447:455	dolichol phosphate	438:455	dolichol phosphate by sequential enzymatic reactions	438:489	The N-glycan precursor is biosynthesized in the endoplasmic reticulum (ER) from dolichol phosphate by sequential enzymatic reactions to generate the dolichol-linked oligosaccharide composed of 14 sugar residues, Glc3Man9GlcNAc2.
34495528	6	44	theme	folding	795:801	arg1	step					803:806	the folding step	791:806	the folding step	791:806	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	5	45	theme	nascent	717:723	arg1	proteins					725:732	nascent proteins	717:732	nascent proteins	717:732	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	5	46	theme	en	615:616	arg1	oligosaccharide					591:605	The oligosaccharide	587:605	The oligosaccharide	587:605	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	5	46	theme	en	615:616	arg1	bloc					618:621	en bloc	615:621	en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins	615:732	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	7	47	theme	misfolded	1055:1063	arg1	glycoproteins					1065:1077	these misfolded glycoproteins	1049:1077	these misfolded glycoproteins	1049:1077	Despite the N-glycan-dependent folding process, some glycoproteins do not fold correctly, and these misfolded glycoproteins are destined to degradation by proteasomes in the cytosol.
34495528	5	48	dep	N-X-S/T	661:667	arg1	represents					672:681	represents	672:681	represents any amino acid except proline	672:711	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	5	49	theme	proteins	725:732	arg1	N-X-S/T					661:667	the consensus sequence N-X-S/T	638:667	the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins	638:732	The oligosaccharide is then en bloc transferred to the consensus sequence N-X-S/T (X represents any amino acid except proline) of nascent proteins.
34495528	6	50	theme	protein	872:878	arg1	fold					880:883	the correct protein fold	860:883	the correct protein fold	860:883	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	9	51	dep	N-Acetylglucosaminyltransferases	1331:1362	arg1	GnT-V					1386:1390	GnT-V	1386:1390	GnT-V	1386:1390	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V) produce branched N-glycan structures, affording a higher complexity to N-glycans.
34495528	9	51	dep	N-Acetylglucosaminyltransferases	1331:1362	arg1	GnT-III					1365:1371	GnT-III	1365:1371	GnT-III	1365:1371	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V) produce branched N-glycan structures, affording a higher complexity to N-glycans.
34495528	9	51	dep	N-Acetylglucosaminyltransferases	1331:1362	arg1	N-Acetylglucosaminyltransferases					1331:1362	N-Acetylglucosaminyltransferases	1331:1362	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V)	1331:1391	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V) produce branched N-glycan structures, affording a higher complexity to N-glycans.
34495528	9	51	dep	N-Acetylglucosaminyltransferases	1331:1362	arg1	GnT-IV					1374:1379	GnT-IV	1374:1379	GnT-IV	1374:1379	N-Acetylglucosaminyltransferases (GnT-III, GnT-IV, and GnT-V) produce branched N-glycan structures, affording a higher complexity to N-glycans.
34495528	6	52	theme	correct	864:870	arg1	fold					880:883	the correct protein fold	860:883	the correct protein fold	860:883	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	1	53	theme	conserved	45:53	arg1	N-glycosylation					17:31	N-glycosylation	17:31	N-glycosylation	17:31	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	1	53	theme	conserved	45:53	arg1	modification					62:73	a highly conserved glycan modification	36:73	a highly conserved glycan modification	36:73	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	6	54	gly	N-glycosylated	753:766	arg1	proteins					776:783	the N-glycosylated nascent proteins	749:783	the N-glycosylated nascent proteins	749:783	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	1	55	theme	glycan	55:60	arg1	N-glycosylation					17:31	N-glycosylation	17:31	N-glycosylation	17:31	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	1	55	theme	glycan	55:60	arg1	modification					62:73	a highly conserved glycan modification	36:73	a highly conserved glycan modification	36:73	N-glycosylation is a highly conserved glycan modification, and more than 7000 proteins are N-glycosylated in humans.
34495528	6	56	theme	nascent	768:774	arg1	proteins					776:783	the N-glycosylated nascent proteins	749:783	the N-glycosylated nascent proteins	749:783	Subsequently, the N-glycosylated nascent proteins enter the folding step, in which N-glycans contribute largely to attaining the correct protein fold by recruiting the lectin-like chaperones, calnexin, and calreticulin.
34495528	2	57	contain	has	150:152	arg2	functions					170:178	many biological functions	154:178	many biological functions such as protein folding, trafficking, and signal transduction	154:240	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	57	contain	has	150:152	arg2	trafficking					205:215	trafficking	205:215	trafficking	205:215	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	57	contain	has	150:152	arg2	folding					196:202	protein folding	188:202	protein folding	188:202	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	57	contain	has	150:152	arg1	N-glycosylation					134:148	N-glycosylation	134:148	N-glycosylation	134:148	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	2	57	contain	has	150:152	arg2	transduction					229:240	signal transduction	222:240	signal transduction	222:240	N-glycosylation has many biological functions such as protein folding, trafficking, and signal transduction.
34495528	7	58	gly	glycoproteins	1065:1077	arg1	glycoproteins					1065:1077	these misfolded glycoproteins	1049:1077	these misfolded glycoproteins	1049:1077	Despite the N-glycan-dependent folding process, some glycoproteins do not fold correctly, and these misfolded glycoproteins are destined to degradation by proteasomes in the cytosol.
32366695	6	0	theme	glycan	852:857	arg1	processing					859:868	typical host glycan processing	839:868	typical host glycan processing	839:868	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	6	1	theme	S	817:817	arg1	glycans					819:825	SARS-CoV-2 S glycans	806:825	SARS-CoV-2 S glycans	806:825	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	6	2	theme	host	847:850	arg1	processing					859:868	typical host glycan processing	839:868	typical host glycan processing	839:868	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	2	3	gly	glycoprotein	373:384	arg1	target					320:325	the principal target	306:325	the principal target of the humoral immune response	306:356	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	2	3	gly	glycoprotein	373:384	arg1	glycoprotein					373:384	the spike (S) glycoprotein	359:384	the spike (S) glycoprotein	359:384	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	1	4	theme	considerable	228:239	arg1	threat					241:246	a considerable threat	226:246	a considerable threat to global human health	226:269	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	6	5	theme	typical	839:845	arg1	processing					859:868	typical host glycan processing	839:868	typical host glycan processing	839:868	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	2	6	theme	Vaccine	272:278	arg1	development					280:290	Vaccine development	272:290	Vaccine development	272:290	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	6	7	theme	vaccine	925:931	arg1	design					933:938	vaccine design	925:938	vaccine design	925:938	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	4	8	theme	recombinant	663:673	arg1	immunogen					688:696	a recombinant SARS-CoV-2 S immunogen	661:696	a recombinant SARS-CoV-2 S immunogen	661:696	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	3	9	theme	SARS-CoV-2	438:447	arg1	sequons					483:489	22 N-linked glycan sequons	464:489	22 N-linked glycan sequons	464:489	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	3	9	theme	SARS-CoV-2	438:447	arg1	gene					451:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	5	10	theme	viral	781:785	arg1	spike					787:791	the trimeric viral spike	768:791	the trimeric viral spike	768:791	This analysis enables mapping of the glycan-processing states across the trimeric viral spike.
32366695	3	11	theme	glycan	476:481	arg1	sequons					483:489	22 N-linked glycan sequons	464:489	22 N-linked glycan sequons	464:489	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	3	11	theme	glycan	476:481	arg1	gene					451:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	2	12	theme	spike	363:367	arg1	target					320:325	the principal target	306:325	the principal target of the humoral immune response	306:356	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	2	12	theme	spike	363:367	arg1	glycoprotein					373:384	the spike (S) glycoprotein	359:384	the spike (S) glycoprotein	359:384	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	5	13	theme	glycan-processing	736:752	arg1	states					754:759	the glycan-processing states	732:759	the glycan-processing states	732:759	This analysis enables mapping of the glycan-processing states across the trimeric viral spike.
32366695	5	14	theme	states	754:759	arg1	mapping					721:727	mapping	721:727	mapping of the glycan-processing states across the trimeric viral spike	721:791	This analysis enables mapping of the glycan-processing states across the trimeric viral spike.
32366695	1	15	theme	causative	159:167	arg1	agent					169:173	the causative agent	155:173	the causative agent of coronavirus disease 2019 (COVID-19)	155:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	15	theme	causative	159:167	arg1	coronavirus					127:137	the betacoronavirus, severe acute respiratory syndrome coronavirus 2	72:139	coronavirus	127:137	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	0	16	theme	glycan	14:19	arg1	analysis					21:28	Site-specific glycan analysis	0:28	Site-specific glycan analysis of the SARS-CoV-2	0:46	Site-specific glycan analysis of the SARS-CoV-2 spike.
32366695	3	17	theme	N-linked	467:474	arg1	sequons					483:489	22 N-linked glycan sequons	464:489	22 N-linked glycan sequons	464:489	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	3	17	theme	N-linked	467:474	arg1	gene					451:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	1	18	theme	betacoronavirus	76:90	arg1	coronavirus					127:137	the betacoronavirus, severe acute respiratory syndrome coronavirus 2	72:139	coronavirus	127:137	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	18	theme	betacoronavirus	76:90	arg1	agent					169:173	the causative agent	155:173	the causative agent of coronavirus disease 2019 (COVID-19)	155:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	18	theme	betacoronavirus	76:90	arg1	SARS-CoV-2					142:151	SARS-CoV-2	142:151	SARS-CoV-2	142:151	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	4	19	theme	spectrometric	602:614	arg1	approach					616:623	a site-specific mass spectrometric approach	581:623	a site-specific mass spectrometric approach	581:623	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	0	20	theme	Site-specific	0:12	arg1	analysis					21:28	Site-specific glycan analysis	0:28	Site-specific glycan analysis of the SARS-CoV-2	0:46	Site-specific glycan analysis of the SARS-CoV-2 spike.
32366695	1	21	theme	global	251:256	arg1	health					264:269	global human health	251:269	global human health	251:269	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	4	22	theme	site-specific	583:595	arg1	approach					616:623	a site-specific mass spectrometric approach	581:623	a site-specific mass spectrometric approach	581:623	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	2	23	theme	response	349:356	arg1	target					320:325	the principal target	306:325	the principal target of the humoral immune response	306:356	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	2	23	theme	response	349:356	arg1	glycoprotein					373:384	the spike (S) glycoprotein	359:384	the spike (S) glycoprotein	359:384	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	1	24	theme	human	258:262	arg1	health					264:269	global human health	251:269	global human health	251:269	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	25	theme	severe	93:98	arg1	coronavirus					127:137	the betacoronavirus, severe acute respiratory syndrome coronavirus 2	72:139	coronavirus	127:137	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	25	theme	severe	93:98	arg1	agent					169:173	the causative agent	155:173	the causative agent of coronavirus disease 2019 (COVID-19)	155:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	25	theme	severe	93:98	arg1	SARS-CoV-2					142:151	SARS-CoV-2	142:151	SARS-CoV-2	142:151	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	26	theme	coronavirus	178:188	arg1	disease					190:196	coronavirus disease 2019	178:201	coronavirus disease 2019 (COVID-19)	178:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	26	theme	coronavirus	178:188	arg1	COVID-19					204:211	COVID-19	204:211	COVID-19	204:211	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	6	27	theme	SARS-CoV-2	806:815	arg1	glycans					819:825	SARS-CoV-2 S glycans	806:825	SARS-CoV-2 S glycans	806:825	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	1	28	theme	acute	100:104	arg1	coronavirus					127:137	the betacoronavirus, severe acute respiratory syndrome coronavirus 2	72:139	coronavirus	127:137	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	28	theme	acute	100:104	arg1	agent					169:173	the causative agent	155:173	the causative agent of coronavirus disease 2019 (COVID-19)	155:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	28	theme	acute	100:104	arg1	SARS-CoV-2					142:151	SARS-CoV-2	142:151	SARS-CoV-2	142:151	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	29	theme	disease	190:196	arg1	agent					169:173	the causative agent	155:173	the causative agent of coronavirus disease 2019 (COVID-19)	155:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	29	theme	disease	190:196	arg1	coronavirus					127:137	the betacoronavirus, severe acute respiratory syndrome coronavirus 2	72:139	coronavirus	127:137	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	0	30	theme	SARS-CoV-2	37:46	arg1	analysis					21:28	Site-specific glycan analysis	0:28	Site-specific glycan analysis of the SARS-CoV-2	0:46	Site-specific glycan analysis of the SARS-CoV-2 spike.
32366695	2	31	theme	principal	310:318	arg1	target					320:325	the principal target	306:325	the principal target of the humoral immune response	306:356	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	2	31	theme	principal	310:318	arg1	glycoprotein					373:384	the spike (S) glycoprotein	359:384	the spike (S) glycoprotein	359:384	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	4	32	theme	mass	597:600	arg1	approach					616:623	a site-specific mass spectrometric approach	581:623	a site-specific mass spectrometric approach	581:623	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	2	33	theme	S	370:370	arg1	target					320:325	the principal target	306:325	the principal target of the humoral immune response	306:356	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	2	33	theme	S	370:370	arg1	glycoprotein					373:384	the spike (S) glycoprotein	359:384	the spike (S) glycoprotein	359:384	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	2	34	theme	membrane	417:424	arg1	fusion					426:431	membrane fusion	417:431	membrane fusion	417:431	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	3	35	link	N-linked	467:474	arg1	sequons					483:489	22 N-linked glycan sequons	464:489	22 N-linked glycan sequons	464:489	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	3	35	link	N-linked	467:474	arg1	gene					451:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	3	36	theme	protein	533:539	arg1	folding					541:547	protein folding	533:547	protein folding	533:547	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	6	37	theme	viral	902:906	arg1	pathobiology					908:919	viral pathobiology	902:919	viral pathobiology	902:919	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	1	38	theme	respiratory	106:116	arg1	coronavirus					127:137	the betacoronavirus, severe acute respiratory syndrome coronavirus 2	72:139	coronavirus	127:137	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	38	theme	respiratory	106:116	arg1	agent					169:173	the causative agent	155:173	the causative agent of coronavirus disease 2019 (COVID-19)	155:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	38	theme	respiratory	106:116	arg1	SARS-CoV-2					142:151	SARS-CoV-2	142:151	SARS-CoV-2	142:151	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	39	theme	syndrome	118:125	arg1	coronavirus					127:137	the betacoronavirus, severe acute respiratory syndrome coronavirus 2	72:139	coronavirus	127:137	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	39	theme	syndrome	118:125	arg1	agent					169:173	the causative agent	155:173	the causative agent of coronavirus disease 2019 (COVID-19)	155:212	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	1	39	theme	syndrome	118:125	arg1	SARS-CoV-2					142:151	SARS-CoV-2	142:151	SARS-CoV-2	142:151	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	4	40	theme	glycan	640:645	arg1	structures					647:656	the glycan structures	636:656	the glycan structures on a recombinant SARS-CoV-2 S immunogen	636:696	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	3	41	theme	immune	553:558	arg1	evasion					560:566	immune evasion	553:566	immune evasion	553:566	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	1	42	theme	coronavirus	127:137	arg1	emergence					59:67	The emergence	55:67	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19),	55:213	The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health.
32366695	4	43	theme	S	686:686	arg1	immunogen					688:696	a recombinant SARS-CoV-2 S immunogen	661:696	a recombinant SARS-CoV-2 S immunogen	661:696	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	4	44	theme	SARS-CoV-2	675:684	arg1	immunogen					688:696	a recombinant SARS-CoV-2 S immunogen	661:696	a recombinant SARS-CoV-2 S immunogen	661:696	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	2	45	theme	humoral	334:340	arg1	response					349:356	the humoral immune response	330:356	the humoral immune response	330:356	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	5	46	theme	trimeric	772:779	arg1	spike					787:791	the trimeric viral spike	768:791	the trimeric viral spike	768:791	This analysis enables mapping of the glycan-processing states across the trimeric viral spike.
32366695	2	47	theme	immune	342:347	arg1	response					349:356	the humoral immune response	330:356	the humoral immune response	330:356	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	4	48	from	structures	647:656	arg1	immunogen					688:696	a recombinant SARS-CoV-2 S immunogen	661:696	a recombinant SARS-CoV-2 S immunogen	661:696	Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen.
32366695	6	49	contain	have	881:884	arg1	which					871:875	which	871:875	which	871:875	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	6	49	contain	have	881:884	arg2	implications					886:897	implications	886:897	implications	886:897	We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
32366695	2	50	theme	cell	402:405	arg1	entry					407:411	cell entry	402:411	cell entry	402:411	Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
32366695	3	51	theme	S	449:449	arg1	sequons					483:489	22 N-linked glycan sequons	464:489	22 N-linked glycan sequons	464:489	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
32366695	3	51	theme	S	449:449	arg1	gene					451:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene	434:454	The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion.
33103998	9	0	theme	biosynthesis	978:989	arg1	inhibition					955:964	inhibition	955:964	inhibition of N-glycan biosynthesis	955:989	Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis.
33103998	6	1	theme	viral	754:758	arg1	entry					760:764	viral entry	754:764	viral entry into ACE2 expressing HEK293T cells	754:799	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	8	2	theme	multiple	896:903	arg1	roles					905:909	multiple roles	896:909	multiple roles for glycans	896:921	Mechanistic studies suggest multiple roles for glycans during viral entry.
33103998	3	3	theme	different	309:317	arg1	glycoforms					319:328	different glycoforms	309:328	different glycoforms of the Spike-protein and ACE2	309:358	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	9	4	theme	Spike-protein	1000:1012	arg1	proteolysis					1014:1024	Spike-protein proteolysis	1000:1024	Spike-protein proteolysis	1000:1024	Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis.
33103998	4	5	theme	Spike-ACE2	515:524	arg1	binding					526:532	Spike-ACE2 binding	515:532	Spike-ACE2 binding	515:532	We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding.
33103998	1	6	gly	glycosylated	194:205	arg1	ACE2					173:176	its primary receptor ACE2	152:176	its primary receptor ACE2	152:176	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	6	gly	glycosylated	194:205	arg1	SARS-CoV-2					101:110	SARS-CoV-2	101:110	SARS-CoV-2	101:110	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	6	gly	glycosylated	194:205	arg1	protein					90:96	The Spike protein	80:96	The Spike protein of SARS-CoV-2	80:110	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	6	gly	glycosylated	194:205	arg1	RBD					142:144	RBD	142:144	RBD	142:144	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	6	gly	glycosylated	194:205	arg1	domain					134:139	its receptor-binding domain	113:139	its receptor-binding domain (RBD)	113:145	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	3	7	theme	ACE2	355:358	arg1	glycoforms					319:328	different glycoforms	309:328	different glycoforms of the Spike-protein and ACE2	309:358	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	8	8	theme	viral	930:934	arg1	entry					936:940	viral entry	930:940	viral entry	930:940	Mechanistic studies suggest multiple roles for glycans during viral entry.
33103998	4	9	contain	had	484:486	arg1	O-glycans					474:482	O-glycans	474:482	O-glycans	474:482	We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding.
33103998	4	9	contain	had	484:486	arg1	N-					467:468	N-	467:468	N-	467:468	We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding.
33103998	4	9	contain	had	484:486	arg2	contribution					499:510	only minor contribution	488:510	only minor contribution	488:510	We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding.
33103998	2	10	theme	viral	262:266	arg1	entry					268:272	viral entry	262:272	viral entry	262:272	The impact of this post-translational modification on viral entry is yet unestablished.
33103998	3	11	theme	Spike-protein	337:349	arg1	glycoforms					319:328	different glycoforms	309:328	different glycoforms of the Spike-protein and ACE2	309:358	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	4	12	theme	minor	493:497	arg1	contribution					499:510	only minor contribution	488:510	only minor contribution	488:510	We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding.
33103998	8	13	theme	Mechanistic	868:878	arg1	studies					880:886	Mechanistic studies	868:886	Mechanistic studies	868:886	Mechanistic studies suggest multiple roles for glycans during viral entry.
33103998	2	14	from	impact	212:217	arg1	entry					268:272	viral entry	262:272	viral entry	262:272	The impact of this post-translational modification on viral entry is yet unestablished.
33103998	11	15	theme	chemical	1139:1146	arg1	inhibitors					1148:1157	chemical inhibitors	1139:1157	chemical inhibitors of glycosylation	1139:1174	Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.
33103998	3	16	theme	glycoengineered	375:389	arg1	cells					391:395	CRISPR-Cas9 glycoengineered cells	363:395	CRISPR-Cas9 glycoengineered cells	363:395	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	3	17	dep	Spike-protein	337:349	arg1	the					333:335	the	333:335	the	333:335	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	3	18	theme	SARS-CoV-2	426:435	arg1	pseudovirus					437:447	corresponding SARS-CoV-2 pseudovirus	412:447	corresponding SARS-CoV-2 pseudovirus	412:447	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	7	19	theme	viral	855:859	arg1	entry					861:865	viral entry	855:865	viral entry	855:865	Blocking O-glycan elaboration also partially blocked viral entry.
33103998	11	20	theme	glycosylation	1162:1174	arg1	inhibitors					1148:1157	chemical inhibitors	1139:1157	chemical inhibitors of glycosylation	1139:1174	Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.
33103998	1	21	theme	Spike	84:88	arg1	protein					90:96	The Spike protein	80:96	The Spike protein of SARS-CoV-2	80:110	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	6	22	theme	small	706:710	arg1	kifunensine					721:731	the small molecule kifunensine	702:731	the small molecule kifunensine	702:731	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	1	23	theme	primary	156:162	arg1	ACE2					173:176	its primary receptor ACE2	152:176	its primary receptor ACE2	152:176	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	0	24	theme	viral	25:29	arg1	entry					31:35	SARS-CoV-2 viral entry	14:35	SARS-CoV-2 viral entry	14:35	Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration.
33103998	5	25	theme	viral	598:602	arg1	entry					604:608	viral entry	598:608	viral entry	598:608	However, these carbohydrates played a major role in regulating viral entry.
33103998	1	26	theme	receptor	164:171	arg1	ACE2					173:176	its primary receptor ACE2	152:176	its primary receptor ACE2	152:176	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	3	27	theme	CRISPR-Cas9	363:373	arg1	cells					391:395	CRISPR-Cas9 glycoengineered cells	363:395	CRISPR-Cas9 glycoengineered cells	363:395	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	6	28	theme	molecule	712:719	arg1	kifunensine					721:731	the small molecule kifunensine	702:731	the small molecule kifunensine	702:731	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	10	29	theme	host	1092:1095	arg1	ACE2					1097:1100	host ACE2	1092:1100	host ACE2	1092:1100	This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry.
33103998	0	30	dep	N-	51:52	arg1	elaboration					67:77	elaboration	67:77	elaboration	67:77	Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration.
33103998	0	31	theme	entry	31:35	arg1	Inhibition					0:9	Inhibition	0:9	Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration.	0:78	Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration.
33103998	3	32	theme	corresponding	412:424	arg1	pseudovirus					437:447	corresponding SARS-CoV-2 pseudovirus	412:447	corresponding SARS-CoV-2 pseudovirus	412:447	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	10	33	theme	RBD	1045:1047	arg1	presentation					1049:1060	RBD presentation	1045:1060	RBD presentation	1045:1060	This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry.
33103998	1	34	theme	SARS-CoV-2	101:110	arg1	ACE2					173:176	its primary receptor ACE2	152:176	its primary receptor ACE2	152:176	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	34	theme	SARS-CoV-2	101:110	arg1	SARS-CoV-2					101:110	SARS-CoV-2	101:110	SARS-CoV-2	101:110	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	34	theme	SARS-CoV-2	101:110	arg1	protein					90:96	The Spike protein	80:96	The Spike protein of SARS-CoV-2	80:110	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	34	theme	SARS-CoV-2	101:110	arg1	RBD					142:144	RBD	142:144	RBD	142:144	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	34	theme	SARS-CoV-2	101:110	arg1	domain					134:139	its receptor-binding domain	113:139	its receptor-binding domain (RBD)	113:145	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	7	35	theme	Blocking	802:809	arg1	elaboration					820:830	Blocking O-glycan elaboration	802:830	Blocking O-glycan elaboration	802:830	Blocking O-glycan elaboration also partially blocked viral entry.
33103998	3	36	gly	glycoforms	319:328	arg1	Spike-protein					337:349	Spike-protein	337:349	Spike-protein	337:349	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	3	36	gly	glycoforms	319:328	arg1	ACE2					355:358	ACE2	355:358	ACE2	355:358	We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus.
33103998	6	37	theme	HEK293T	787:793	arg1	cells					795:799	ACE2 expressing HEK293T cells	771:799	ACE2 expressing HEK293T cells	771:799	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	6	38	theme	genetic	679:685	arg1	approaches					687:696	genetic approaches	679:696	genetic approaches	679:696	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	7	39	theme	O-glycan	811:818	arg1	elaboration					820:830	Blocking O-glycan elaboration	802:830	Blocking O-glycan elaboration	802:830	Blocking O-glycan elaboration also partially blocked viral entry.
33103998	10	40	theme	viral	1117:1121	arg1	entry					1123:1127	viral entry	1117:1127	viral entry	1117:1127	This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry.
33103998	2	41	theme	modification	246:257	arg1	impact					212:217	The impact	208:217	The impact of this post-translational modification on viral entry	208:272	The impact of this post-translational modification on viral entry is yet unestablished.
33103998	5	42	theme	major	573:577	arg1	role					579:582	a major role	571:582	a major role	571:582	However, these carbohydrates played a major role in regulating viral entry.
33103998	6	43	theme	expressing	776:785	arg1	cells					795:799	ACE2 expressing HEK293T cells	771:799	ACE2 expressing HEK293T cells	771:799	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	2	44	theme	post-translational	227:244	arg1	modification					246:257	this post-translational modification	222:257	this post-translational modification	222:257	The impact of this post-translational modification on viral entry is yet unestablished.
33103998	6	45	theme	ACE2	771:774	arg1	cells					795:799	ACE2 expressing HEK293T cells	771:799	ACE2 expressing HEK293T cells	771:799	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	1	46	theme	receptor-binding	117:132	arg1	SARS-CoV-2					101:110	SARS-CoV-2	101:110	SARS-CoV-2	101:110	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	46	theme	receptor-binding	117:132	arg1	RBD					142:144	RBD	142:144	RBD	142:144	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	1	46	theme	receptor-binding	117:132	arg1	domain					134:139	its receptor-binding domain	113:139	its receptor-binding domain (RBD)	113:145	The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated.
33103998	10	47	dep	reduce	1038:1043	arg1	decreasing					1106:1115	decreasing	1106:1115	decreasing viral entry	1106:1127	This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry.
33103998	10	47	dep	reduce	1038:1043	arg1	lowering					1072:1079	lowering	1072:1079	lowering binding to host ACE2	1072:1100	This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry.
33103998	9	48	theme	N-glycan	969:976	arg1	biosynthesis					978:989	N-glycan biosynthesis	969:989	N-glycan biosynthesis	969:989	Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis.
33103998	0	49	theme	SARS-CoV-2	14:23	arg1	entry					31:35	SARS-CoV-2 viral entry	14:35	SARS-CoV-2 viral entry	14:35	Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration.
33103998	6	50	theme	N-glycan	620:627	arg1	biosynthesis					629:640	N-glycan biosynthesis	620:640	N-glycan biosynthesis	620:640	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
33103998	6	51	theme	oligomannose	649:660	arg1	stage					662:666	the oligomannose stage	645:666	the oligomannose stage using both genetic approaches and the small molecule kifunensine	645:731	Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells.
34278967	4	0	theme	mutant	943:948	arg1	variants					1100:1107	the epidemic variants	1087:1107	the epidemic variants B.1.1.7, B.1.351, and P.1	1087:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	0	theme	mutant	943:948	arg1	mutants					997:1003	the artificial mutants	982:1003	the artificial mutants at N-/O-linked glycosylation site	982:1037	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	0	theme	mutant	943:948	arg1	strains					950:956	mutant strains	943:956	mutant strains	943:956	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	0	theme	mutant	943:948	arg1	mutants					1067:1073	natural existed amino acid mutants	1040:1073	natural existed amino acid mutants	1040:1073	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	8	1	theme	single	1680:1685	arg1	experiment					1703:1712	single injection mouse experiment	1680:1712	single injection mouse experiment	1680:1712	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	6	2	theme	infection	1324:1332	arg1	steps					1315:1319	the early steps	1305:1319	the early steps of infection	1305:1332	We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection.
34278967	7	3	theme	spectrum	1519:1526	arg1	activity					1544:1551	the observed broad spectrum anti-SARS-CoV-2 activity	1500:1551	the observed broad spectrum anti-SARS-CoV-2 activity	1500:1551	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	8	4	theme	mouse	1697:1701	arg1	experiment					1703:1712	single injection mouse experiment	1680:1712	single injection mouse experiment	1680:1712	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	7	5	theme	observed	1504:1511	arg1	spectrum					1519:1526	the observed broad spectrum	1500:1526	the observed broad spectrum anti-SARS-CoV-2 activity	1500:1551	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	8	6	located	found	1671:1675	arg1	experiment					1703:1712	single injection mouse experiment	1680:1712	single injection mouse experiment	1680:1712	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	8	6	located	found	1671:1675	arg2	loss					1662:1665	no weight loss	1652:1665	no weight loss	1652:1665	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	4	7	dep	variants	1100:1107	arg1	variants					1100:1107	the epidemic variants	1087:1107	the epidemic variants B.1.1.7, B.1.351, and P.1	1087:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	7	dep	variants	1100:1107	arg1	B.1.351					1118:1124	B.1.351	1118:1124	B.1.351	1118:1124	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	7	dep	variants	1100:1107	arg1	P.1					1131:1133	P.1	1131:1133	P.1	1131:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	7	dep	variants	1100:1107	arg1	B.1.1.7					1109:1115	B.1.1.7	1109:1115	B.1.1.7	1109:1115	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	3	8	theme	plant-derived	538:550	arg1	lectins					552:558	12 plant-derived lectins	535:558	12 plant-derived lectins with different carbohydrate specificity	535:598	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	1	9	theme	coronavirus	165:175	arg1	protein					120:126	The spike (S) protein	106:126	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously	106:211	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	1	9	theme	coronavirus	165:175	arg1	variants					232:239	newly emerging variants	217:239	newly emerging variants	217:239	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	9	10	theme	first	1740:1744	arg1	evidence					1746:1753	the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies	1736:1911	the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies	1736:1911	This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
34278967	6	11	theme	lentil	1221:1226	arg1	lectin					1228:1233	lentil lectin	1221:1233	lentil lectin	1221:1233	We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection.
34278967	2	12	theme	S	308:308	arg1	protein					310:316	S protein	308:316	S protein	308:316	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	4	13	theme	N-/O-linked	1008:1018	arg1	site					1034:1037	N-/O-linked glycosylation site	1008:1037	N-/O-linked glycosylation site	1008:1037	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	5	14	theme	Lentil	1136:1141	arg1	lectin					1143:1148	Lentil lectin	1136:1148	Lentil lectin	1136:1148	Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV.
34278967	4	15	theme	amino	1056:1060	arg1	acid					1062:1065	existed amino acid	1048:1065	natural existed amino acid mutants	1040:1073	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	7	16	theme	S	1399:1399	arg1	trimer					1401:1406	S trimer	1399:1406	S trimer	1399:1406	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	4	17	theme	Lens	742:745	arg1	lectin					772:777	The Lens culinaris-derived lentil lectin	738:777	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus	738:874	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	18	from	site	1034:1037	arg1	mutants					997:1003	the artificial mutants	982:1003	the artificial mutants at N-/O-linked glycosylation site	982:1037	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	18	from	site	1034:1037	arg1	B.1.351					1118:1124	B.1.351	1118:1124	B.1.351	1118:1124	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	18	from	site	1034:1037	arg1	mutants					1067:1073	natural existed amino acid mutants	1040:1073	natural existed amino acid mutants	1040:1073	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	18	from	site	1034:1037	arg1	variants					1100:1107	the epidemic variants	1087:1107	the epidemic variants B.1.1.7, B.1.351, and P.1	1087:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	18	from	site	1034:1037	arg1	P.1					1131:1133	P.1	1131:1133	P.1	1131:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	18	from	site	1034:1037	arg1	B.1.1.7					1109:1115	B.1.1.7	1109:1115	B.1.1.7	1109:1115	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	3	19	theme	mutant	653:658	arg1	strains					660:666	mutant strains	653:666	mutant strains	653:666	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	1	20	theme	severe	131:136	arg1	coronavirus					165:175	severe acute respiratory syndrome coronavirus 2	131:177	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	131:190	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	1	20	theme	severe	131:136	arg1	SARS-CoV-2					180:189	SARS-CoV-2	180:189	SARS-CoV-2	180:189	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	9	21	theme	lentil	1760:1765	arg1	lectin					1767:1772	lentil lectin	1760:1772	lentil lectin	1760:1772	This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
34278967	4	22	theme	lentil	765:770	arg1	lectin					772:777	The Lens culinaris-derived lentil lectin	738:777	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus	738:874	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	1	23	theme	respiratory	144:154	arg1	coronavirus					165:175	severe acute respiratory syndrome coronavirus 2	131:177	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	131:190	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	1	23	theme	respiratory	144:154	arg1	SARS-CoV-2					180:189	SARS-CoV-2	180:189	SARS-CoV-2	180:189	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	4	24	theme	natural	1040:1046	arg1	mutants					1067:1073	natural existed amino acid mutants	1040:1073	natural existed amino acid mutants	1040:1073	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	8	25	theme	weak	1575:1578	arg1	activity					1598:1605	weak haemagglutination activity	1575:1605	weak haemagglutination activity	1575:1605	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	4	26	theme	non-reducing	850:861	arg1	terminus					867:874	the non-reducing end terminus	846:874	the non-reducing end terminus	846:874	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	5	27	theme	antiviral	1162:1170	arg1	activity					1172:1179	antiviral activity	1162:1179	antiviral activity against SARS-CoV and MERS-CoV	1162:1209	Lentil lectin also showed antiviral activity against SARS-CoV and MERS-CoV.
34278967	4	28	theme	epidemic	1091:1098	arg1	variants					1100:1107	the epidemic variants	1087:1107	the epidemic variants B.1.1.7, B.1.351, and P.1	1087:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	28	theme	epidemic	1091:1098	arg1	B.1.351					1118:1124	B.1.351	1118:1124	B.1.351	1118:1124	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	28	theme	epidemic	1091:1098	arg1	P.1					1131:1133	P.1	1131:1133	P.1	1131:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	28	theme	epidemic	1091:1098	arg1	B.1.1.7					1109:1115	B.1.1.7	1109:1115	B.1.1.7	1109:1115	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	9	29	theme	variants	1815:1822	arg1	infection					1791:1799	infection	1791:1799	infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies	1791:1911	This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
34278967	4	30	theme	oligomannose-type	806:822	arg1	glycans					824:830	oligomannose-type glycans	806:830	oligomannose-type glycans	806:830	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	0	31	theme	Lentil	0:5	arg1	lectin					7:12	Lentil lectin	0:12	Lentil lectin derived from Lens culinaris	0:40	Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants.
34278967	7	32	theme	N-glycan	1379:1386	arg1	profile					1388:1394	N-glycan profile	1379:1394	N-glycan profile of S trimer	1379:1406	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	9	33	theme	anti-SARS-CoV-2	1886:1900	arg1	strategies					1902:1911	future anti-SARS-CoV-2 strategies	1879:1911	future anti-SARS-CoV-2 strategies	1879:1911	This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
34278967	1	34	theme	spike	110:114	arg1	protein					120:126	The spike (S) protein	106:126	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously	106:211	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	2	35	theme	anti-SARS-CoV-2	471:485	arg1	strategies					487:496	anti-SARS-CoV-2 strategies	471:496	anti-SARS-CoV-2 strategies against variants	471:513	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	2	36	theme	protein	414:420	arg1	surface					422:428	S protein surface	412:428	S protein surface	412:428	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	7	37	theme	structural	1341:1350	arg1	information					1352:1362	structural information	1341:1362	structural information	1341:1362	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	0	38	theme	antiviral	56:64	arg1	activities					66:75	broad antiviral activities	50:75	broad antiviral activities against SARS-CoV-2 variants	50:103	Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants.
34278967	4	39	theme	antiviral	905:913	arg1	activity					915:922	most potent and broad antiviral activity	883:922	most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1	883:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	2	40	theme	glycosylation	350:362	arg1	sites					364:368	the glycosylation sites	346:368	the glycosylation sites	346:368	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	2	41	gly	glycosylated	329:340	arg1	protein					310:316	S protein	308:316	S protein	308:316	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	8	42	theme	weight	1655:1660	arg1	loss					1662:1665	no weight loss	1652:1665	no weight loss	1652:1665	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	4	43	link	N-/O-linked	1008:1018	arg1	site					1034:1037	N-/O-linked glycosylation site	1008:1037	N-/O-linked glycosylation site	1008:1037	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	3	44	theme	neutralization	716:729	arg1	assay					731:735	a pseudovirus-based neutralization assay	696:735	a pseudovirus-based neutralization assay	696:735	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	1	45	theme	emerging	223:230	arg1	variants					232:239	newly emerging variants	217:239	newly emerging variants	217:239	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	0	46	theme	broad	50:54	arg1	activities					66:75	broad antiviral activities	50:75	broad antiviral activities against SARS-CoV-2 variants	50:103	Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants.
34278967	7	47	theme	anti-SARS-CoV-2	1528:1542	arg1	activity					1544:1551	the observed broad spectrum anti-SARS-CoV-2 activity	1500:1551	the observed broad spectrum anti-SARS-CoV-2 activity	1500:1551	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	7	48	theme	broad	1513:1517	arg1	spectrum					1519:1526	the observed broad spectrum	1500:1526	the observed broad spectrum anti-SARS-CoV-2 activity	1500:1551	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	1	49	theme	antibody-mediated	253:269	arg1	neutralization					271:284	antibody-mediated neutralization	253:284	antibody-mediated neutralization raised great concern	253:305	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	7	50	theme	lentil	1462:1467	arg1	lectin					1469:1474	lentil lectin	1462:1474	lentil lectin	1462:1474	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	4	51	theme	strains	950:956	arg1	panel					934:938	a panel	932:938	a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1	932:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	0	52	attach	derived	14:20	arg1	culinaris					32:40	Lens culinaris	27:40	Lens culinaris	27:40	Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants.
34278967	0	52	attach	derived	14:20	arg2	lectin					7:12	Lentil lectin	0:12	Lentil lectin derived from Lens culinaris	0:40	Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants.
34278967	8	53	theme	injection	1687:1695	arg1	experiment					1703:1712	single injection mouse experiment	1680:1712	single injection mouse experiment	1680:1712	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	6	54	theme	early	1309:1313	arg1	steps					1315:1319	the early steps	1305:1319	the early steps of infection	1305:1332	We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection.
34278967	1	55	theme	syndrome	156:163	arg1	coronavirus					165:175	severe acute respiratory syndrome coronavirus 2	131:177	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	131:190	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	1	55	theme	syndrome	156:163	arg1	SARS-CoV-2					180:189	SARS-CoV-2	180:189	SARS-CoV-2	180:189	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	4	56	theme	acid	1062:1065	arg1	mutants					1067:1073	natural existed amino acid mutants	1040:1073	natural existed amino acid mutants	1040:1073	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	4	57	link	culinaris-derived	747:763	arg1	lectin					772:777	The Lens culinaris-derived lentil lectin	738:777	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus	738:874	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	3	58	theme	different	565:573	arg1	specificity					588:598	different carbohydrate specificity	565:598	different carbohydrate specificity	565:598	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	7	59	theme	lectin	1469:1474	arg1	specificity					1447:1457	the carbohydrate specificity	1430:1457	the carbohydrate specificity of lentil lectin	1430:1474	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	4	60	theme	artificial	986:995	arg1	mutants					997:1003	the artificial mutants	982:1003	the artificial mutants at N-/O-linked glycosylation site	982:1037	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	3	61	theme	anti-SARS-CoV-2	620:634	arg1	activity					636:643	their anti-SARS-CoV-2 activity	614:643	their anti-SARS-CoV-2 activity against mutant strains and epidemic variants	614:688	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	7	62	theme	carbohydrate	1434:1445	arg1	specificity					1447:1457	the carbohydrate specificity	1430:1457	the carbohydrate specificity of lentil lectin	1430:1474	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	4	63	theme	variants	962:969	arg1	panel					934:938	a panel	932:938	a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1	932:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	6	64	theme	S	1270:1270	arg1	trimer					1272:1277	S trimer	1270:1277	S trimer	1270:1277	We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection.
34278967	9	65	theme	SARS-COV-2	1804:1813	arg1	variants					1815:1822	SARS-COV-2 variants	1804:1822	SARS-COV-2 variants	1804:1822	This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
34278967	6	66	theme	ACE2	1262:1265	arg1	binding					1251:1257	the binding	1247:1257	the binding of ACE2 to S trimer	1247:1277	We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection.
34278967	4	67	theme	existed	1048:1054	arg1	acid					1062:1065	existed amino acid	1048:1065	natural existed amino acid mutants	1040:1073	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	8	68	theme	Lentil	1554:1559	arg1	lectin					1561:1566	Lentil lectin	1554:1566	Lentil lectin	1554:1566	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	7	69	theme	trimer	1401:1406	arg1	profile					1388:1394	N-glycan profile	1379:1394	N-glycan profile of S trimer	1379:1406	Using structural information and determined N-glycan profile of S trimer, taking together with the carbohydrate specificity of lentil lectin, we provide a basis for the observed broad spectrum anti-SARS-CoV-2 activity.
34278967	1	70	dep	spike	110:114	arg1	S					117:117	S	117:117	S	117:117	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	4	71	theme	glycosylation	1020:1032	arg1	site					1034:1037	N-/O-linked glycosylation site	1008:1037	N-/O-linked glycosylation site	1008:1037	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	0	72	theme	SARS-CoV-2	85:94	arg1	variants					96:103	SARS-CoV-2 variants	85:103	SARS-CoV-2 variants	85:103	Lentil lectin derived from Lens culinaris exhibit broad antiviral activities against SARS-CoV-2 variants.
34278967	1	73	theme	acute	138:142	arg1	coronavirus					165:175	severe acute respiratory syndrome coronavirus 2	131:177	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	131:190	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	1	73	theme	acute	138:142	arg1	SARS-CoV-2					180:189	SARS-CoV-2	180:189	SARS-CoV-2	180:189	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	2	74	theme	strategies	487:496	arg1	development					456:466	the development	452:466	the development of anti-SARS-CoV-2 strategies against variants	452:513	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	4	75	theme	culinaris-derived	747:763	arg1	lectin					772:777	The Lens culinaris-derived lentil lectin	738:777	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus	738:874	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	3	76	theme	carbohydrate	575:586	arg1	specificity					588:598	different carbohydrate specificity	565:598	different carbohydrate specificity	565:598	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	3	77	link	plant-derived	538:550	arg1	lectins					552:558	12 plant-derived lectins	535:558	12 plant-derived lectins with different carbohydrate specificity	535:598	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	8	78	theme	haemagglutination	1580:1596	arg1	activity					1598:1605	weak haemagglutination activity	1575:1605	weak haemagglutination activity	1575:1605	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	4	79	gly	glycosylation	1020:1032	arg2	site					1034:1037	N-/O-linked glycosylation site	1008:1037	N-/O-linked glycosylation site	1008:1037	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	9	80	theme	future	1879:1884	arg1	strategies					1902:1911	future anti-SARS-CoV-2 strategies	1879:1911	future anti-SARS-CoV-2 strategies	1879:1911	This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
34278967	9	81	theme	valuable	1846:1853	arg1	insights					1855:1862	valuable insights	1846:1862	valuable insights for developing future anti-SARS-CoV-2 strategies	1846:1911	This report provides the first evidence that lentil lectin strongly inhibit infection of SARS-COV-2 variants, which should provide valuable insights for developing future anti-SARS-CoV-2 strategies.
34278967	1	82	theme	great	293:297	arg1	concern					299:305	great concern	293:305	great concern	293:305	The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern.
34278967	8	83	theme	cytotoxicity	1625:1636	arg1	activity					1638:1645	no cytotoxicity activity	1622:1645	no cytotoxicity activity	1622:1645	Lentil lectin showed weak haemagglutination activity at 1 mg/mL and no cytotoxicity activity, and no weight loss was found in single injection mouse experiment.
34278967	3	84	theme	epidemic	672:679	arg1	variants					681:688	epidemic variants	672:688	epidemic variants	672:688	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	4	85	theme	potent	888:893	arg1	activity					915:922	most potent and broad antiviral activity	883:922	most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1	883:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	2	86	theme	S	412:412	arg1	surface					422:428	S protein surface	412:428	S protein surface	412:428	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	3	87	with	lectins	552:558	arg1	specificity					588:598	different carbohydrate specificity	565:598	different carbohydrate specificity	565:598	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	2	88	gly	glycosylation	350:362	arg2	sites					364:368	the glycosylation sites	346:368	the glycosylation sites	346:368	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	4	89	theme	broad	899:903	arg1	activity					915:922	most potent and broad antiviral activity	883:922	most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1	883:1133	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	2	90	from	glycans	401:407	arg1	surface					422:428	S protein surface	412:428	S protein surface	412:428	S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants.
34278967	3	91	theme	pseudovirus-based	698:714	arg1	assay					731:735	a pseudovirus-based neutralization assay	696:735	a pseudovirus-based neutralization assay	696:735	Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.
34278967	4	92	theme	end	863:865	arg1	terminus					867:874	the non-reducing end terminus	846:874	the non-reducing end terminus	846:874	The Lens culinaris-derived lentil lectin which specifically bind to oligomannose-type glycans and GlcNAc at the non-reducing end terminus showed most potent and broad antiviral activity against a panel of mutant strains and variants, including the artificial mutants at N-/O-linked glycosylation site, natural existed amino acid mutants, as well as the epidemic variants B.1.1.7, B.1.351, and P.1.
34278967	6	93	from	steps	1315:1319	arg1	SARS-CoV-2					1291:1300	SARS-CoV-2	1291:1300	SARS-CoV-2 at the early steps of infection	1291:1332	We found lentil lectin could block the binding of ACE2 to S trimer and inhibit SARS-CoV-2 at the early steps of infection.
34495532	4	0	from	research	620:627	arg1	diseases					638:645	human diseases	632:645	human diseases due to changes in these types of O-glycosylation	632:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	3	1	theme	importance	303:312	arg1	understanding					282:294	our understanding	278:294	our understanding of the importance of these glycans	278:329	In the last two decades, our understanding of the importance of these glycans has greatly advanced.
34495532	6	2	theme	current	814:820	arg1	view					822:825	the current view	810:825	the current view of the structures	810:843	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	4	3	theme	basic	477:481	arg1	research					483:490	accelerated basic research	465:490	accelerated basic research	465:490	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	4	4	theme	glycosyltransferases	390:409	arg1	identification					368:381	identification	368:381	identification of the glycosyltransferases responsible for the biosynthesis of these glycans	368:459	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	3	5	theme	glycans	323:329	arg1	importance					303:312	the importance	299:312	the importance of these glycans	299:329	In the last two decades, our understanding of the importance of these glycans has greatly advanced.
34495532	4	6	theme	accelerated	465:475	arg1	research					483:490	accelerated basic research	465:490	accelerated basic research	465:490	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	4	7	from	functions	590:598	arg1	diseases					638:645	human diseases	632:645	human diseases due to changes in these types of O-glycosylation	632:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	6	8	theme	O-glycans	875:883	arg1	view					822:825	the current view	810:825	the current view of the structures	810:843	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	6	8	theme	O-glycans	875:883	arg1	significance					853:864	the significance	849:864	the significance of these O-glycans	849:883	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	0	9	theme	Other	0:4	arg1	Types					6:10	Other Types	0:10	Other Types of Glycosylation.	0:28	Other Types of Glycosylation.
34495532	4	10	from	changes	654:660	arg1	types					671:675	these types	665:675	these types of O-glycosylation	665:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	0	11	theme	Glycosylation	15:27	arg1	Types					6:10	Other Types	0:10	Other Types of Glycosylation.	0:28	Other Types of Glycosylation.
34495532	5	12	theme	Notch	706:710	arg1	signaling					721:729	Notch receptor signaling	706:729	Notch receptor signaling	706:729	Notably, Notch receptor signaling is modified with and regulated by these types of O-glycans.
34495532	4	13	theme	due	647:649	arg1	diseases					638:645	human diseases	632:645	human diseases due to changes in these types of O-glycosylation	632:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	4	14	theme	protein	582:588	arg1	functions					590:598	protein functions	582:598	protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation	582:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	5	15	theme	receptor	712:719	arg1	signaling					721:729	Notch receptor signaling	706:729	Notch receptor signaling	706:729	Notably, Notch receptor signaling is modified with and regulated by these types of O-glycans.
34495532	6	16	dep	regulation	926:935	arg1	context					899:905	context	899:905	context	899:905	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	6	16	dep	regulation	926:935	arg1	the					895:897	the	895:897	the	895:897	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	4	17	contain	has	461:463	arg1	identification					368:381	identification	368:381	identification of the glycosyltransferases responsible for the biosynthesis of these glycans	368:459	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	4	17	contain	has	461:463	arg2	research					483:490	accelerated basic research	465:490	accelerated basic research	465:490	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	5	18	theme	O-glycans	780:788	arg1	types					771:775	these types	765:775	these types of O-glycans	765:788	Notably, Notch receptor signaling is modified with and regulated by these types of O-glycans.
34495532	6	19	theme	human	941:945	arg1	diseases					947:954	human diseases	941:954	human diseases	941:954	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	3	20	theme	last	260:263	arg1	decades					269:275	the last two decades	256:275	the last two decades	256:275	In the last two decades, our understanding of the importance of these glycans has greatly advanced.
34495532	2	21	theme	high	158:161	arg1	levels					163:168	the high levels	154:168	the high levels of evolutional conservation	154:196	As suggested by the high levels of evolutional conservation, these O-glycans are fundamentally important for life.
34495532	4	22	theme	molecular	527:535	arg1	mechanisms					537:546	molecular mechanisms	527:546	molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation	527:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	4	23	theme	glycans	453:459	arg1	biosynthesis					431:442	the biosynthesis	427:442	the biosynthesis of these glycans	427:459	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	6	24	theme	Notch	910:914	arg1	regulation					926:935	Notch signaling regulation	910:935	Notch signaling regulation	910:935	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	6	25	theme	structures	834:843	arg1	view					822:825	the current view	810:825	the current view of the structures	810:843	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	6	25	theme	structures	834:843	arg1	significance					853:864	the significance	849:864	the significance of these O-glycans	849:883	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	6	26	theme	signaling	916:924	arg1	regulation					926:935	Notch signaling regulation	910:935	Notch signaling regulation	910:935	Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
34495532	4	27	theme	responsible	411:421	arg1	glycosyltransferases					390:409	the glycosyltransferases	386:409	the glycosyltransferases responsible for the biosynthesis of these glycans	386:459	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	2	28	theme	conservation	185:196	arg1	levels					163:168	the high levels	154:168	the high levels of evolutional conservation	154:196	As suggested by the high levels of evolutional conservation, these O-glycans are fundamentally important for life.
34495532	1	29	theme	O-Linked	30:37	arg1	glycosylation					39:51	O-Linked glycosylation	30:51	O-Linked glycosylation such as O-fucose, O-glucose, and O-N-acetylglucosamine	30:106	O-Linked glycosylation such as O-fucose, O-glucose, and O-N-acetylglucosamine are considered to be unusual.
34495532	4	30	theme	clinical	611:618	arg1	research					620:627	clinical research	611:627	protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation	582:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	2	31	theme	evolutional	173:183	arg1	conservation					185:196	evolutional conservation	173:196	evolutional conservation	173:196	As suggested by the high levels of evolutional conservation, these O-glycans are fundamentally important for life.
34495532	4	32	theme	human	632:636	arg1	diseases					638:645	human diseases	632:645	human diseases due to changes in these types of O-glycosylation	632:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	4	33	theme	functional	499:508	arg1	significance					510:521	the functional significance	495:521	the functional significance	495:521	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
34495532	4	34	theme	O-glycosylation	680:694	arg1	types					671:675	these types	665:675	these types of O-glycosylation	665:694	In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation.
33205259	4	0	from	advancements	609:620	arg1	characterisation					629:644	the characterisation	625:644	the characterisation of glycosylation CQAs of biotherapeutics	625:685	Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics.
33205259	3	1	theme	extensive	385:393	arg1	documentation					395:407	extensive documentation	385:407	extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs)	385:497	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	5	2	theme	biotherapeutic	769:782	arg1	characterisation					792:807	biotherapeutic product characterisation	769:807	biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	769:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	3	3	theme	analyses	430:437	arg1	documentation					395:407	extensive documentation	385:407	extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs)	385:497	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	4	4	theme	tremendous	598:607	arg1	advancements					609:620	tremendous advancements	598:620	tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics	598:685	Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics.
33205259	5	5	theme	product	784:790	arg1	characterisation					792:807	biotherapeutic product characterisation	769:807	biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	769:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	6	theme	perspective	706:716	arg1	overview					718:725	a perspective overview	704:725	a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	704:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	1	7	theme	key	71:73	arg1	Glycosylation					52:64	Glycosylation	52:64	Glycosylation	52:64	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	7	theme	key	71:73	arg1	factor					75:80	a key factor	69:80	a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity	69:236	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	3	8	theme	comprehensive	416:428	arg1	analyses					430:437	the comprehensive analyses	412:437	the comprehensive analyses of glycosylation-related critical quality attributes (CQAs)	412:497	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	5	9	theme	MS-based	734:741	arg1	technologies					743:754	the MS-based technologies	730:754	the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	730:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	3	10	theme	quality	473:479	arg1	CQAs					493:496	CQAs	493:496	CQAs	493:496	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	3	10	theme	quality	473:479	arg1	attributes					481:490	glycosylation-related critical quality attributes	442:490	glycosylation-related critical quality attributes (CQAs)	442:497	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	4	11	theme	Mass	566:569	arg1	spectrometry					571:582	Mass spectrometry	566:582	Mass spectrometry	566:582	Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics.
33205259	1	12	theme	pharmacological	98:112	arg1	properties					114:123	the pharmacological properties	94:123	the pharmacological properties	94:123	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	12	theme	pharmacological	98:112	arg1	solubility					172:181	solubility	172:181	solubility	172:181	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	12	theme	pharmacological	98:112	arg1	immunogenicity					223:236	immunogenicity	223:236	immunogenicity	223:236	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	12	theme	pharmacological	98:112	arg1	bioavailability					184:198	bioavailability	184:198	bioavailability	184:198	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	12	theme	pharmacological	98:112	arg1	stability					161:169	their stability	155:169	their stability	155:169	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	12	theme	pharmacological	98:112	arg1	pharmacokinetics					201:216	pharmacokinetics	201:216	pharmacokinetics	201:216	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	3	13	theme	attributes	481:490	arg1	analyses					430:437	the comprehensive analyses	412:437	the comprehensive analyses of glycosylation-related critical quality attributes (CQAs)	412:497	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	4	14	theme	CQAs	663:666	arg1	characterisation					629:644	the characterisation	625:644	the characterisation of glycosylation CQAs of biotherapeutics	625:685	Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics.
33205259	5	15	theme	relevant	756:763	arg1	technologies					743:754	the MS-based technologies	730:754	the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	730:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	3	16	theme	glycosylation-related	442:462	arg1	CQAs					493:496	CQAs	493:496	CQAs	493:496	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	3	16	theme	glycosylation-related	442:462	arg1	attributes					481:490	glycosylation-related critical quality attributes	442:490	glycosylation-related critical quality attributes (CQAs)	442:497	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	4	17	theme	glycosylation	649:661	arg1	CQAs					663:666	glycosylation CQAs	649:666	glycosylation CQAs of biotherapeutics	649:685	Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics.
33205259	3	18	theme	critical	464:471	arg1	CQAs					493:496	CQAs	493:496	CQAs	493:496	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	3	18	theme	critical	464:471	arg1	attributes					481:490	glycosylation-related critical quality attributes	442:490	glycosylation-related critical quality attributes (CQAs)	442:497	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	4	19	theme	biotherapeutics	671:685	arg1	CQAs					663:666	glycosylation CQAs	649:666	glycosylation CQAs of biotherapeutics	649:685	Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics.
33205259	5	20	theme	recent	833:838	arg1	developments					840:851	the recent developments	829:851	the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	829:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	1	21	theme	biotherapeutics	128:142	arg1	properties					114:123	the pharmacological properties	94:123	the pharmacological properties	94:123	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	21	theme	biotherapeutics	128:142	arg1	solubility					172:181	solubility	172:181	solubility	172:181	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	21	theme	biotherapeutics	128:142	arg1	immunogenicity					223:236	immunogenicity	223:236	immunogenicity	223:236	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	21	theme	biotherapeutics	128:142	arg1	bioavailability					184:198	bioavailability	184:198	bioavailability	184:198	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	21	theme	biotherapeutics	128:142	arg1	stability					161:169	their stability	155:169	their stability	155:169	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	1	21	theme	biotherapeutics	128:142	arg1	pharmacokinetics					201:216	pharmacokinetics	201:216	pharmacokinetics	201:216	Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity.
33205259	5	22	theme	glycosylation	920:932	arg1	linkage					947:953	sialic acid linkage	935:953	sialic acid linkage	935:953	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	22	theme	glycosylation	920:932	arg1	structure					963:971	glycan structure	956:971	glycan structure	956:971	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	22	theme	glycosylation	920:932	arg1	content					978:984	content	978:984	content	978:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	22	theme	glycosylation	920:932	arg1	glycosylation					920:932	glycosylation	920:932	glycosylation	920:932	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	22	theme	glycosylation	920:932	arg1	site					912:915	site	912:915	site of glycosylation	912:932	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	2	23	gly	glycosylation	280:292	arg1	biotherapeutics					297:311	biotherapeutics	297:311	biotherapeutics	297:311	As such, comprehensive information about glycosylation of biotherapeutics is critical to demonstrate similarity.
33205259	3	24	dep	development	510:520	arg1	the					506:508	the	506:508	the	506:508	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	5	25	theme	glycosylation	881:893	arg1	structure					963:971	glycan structure	956:971	glycan structure	956:971	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	25	theme	glycosylation	881:893	arg1	features					895:902	glycosylation features	881:902	glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	881:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	25	theme	glycosylation	881:893	arg1	content					978:984	content	978:984	content	978:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	25	theme	glycosylation	881:893	arg1	site					912:915	site	912:915	site of glycosylation	912:932	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	25	theme	glycosylation	881:893	arg1	linkage					947:953	sialic acid linkage	935:953	sialic acid linkage	935:953	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	25	theme	glycosylation	881:893	arg1	glycosylation					920:932	glycosylation	920:932	glycosylation	920:932	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	2	26	theme	comprehensive	248:260	arg1	information					262:272	comprehensive information	248:272	comprehensive information about glycosylation of biotherapeutics	248:311	As such, comprehensive information about glycosylation of biotherapeutics is critical to demonstrate similarity.
33205259	5	27	theme	sialic	935:940	arg1	linkage					947:953	sialic acid linkage	935:953	sialic acid linkage	935:953	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	28	gly	glycosylation	920:932	arg2	site					912:915	site	912:915	site of glycosylation	912:932	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	28	gly	glycosylation	920:932	arg2	glycosylation					920:932	glycosylation	920:932	glycosylation	920:932	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	3	29	theme	biosimilars	553:563	arg1	manufacturing					523:535	manufacturing	523:535	manufacturing	523:535	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	3	29	theme	biosimilars	553:563	arg1	release					542:548	release	542:548	release	542:548	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	3	29	theme	biosimilars	553:563	arg1	development					510:520	development	510:520	development	510:520	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	5	30	from	emphasis	817:824	arg1	developments					840:851	the recent developments	829:851	the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	829:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	3	31	theme	Regulatory	352:361	arg1	agencies					363:370	Regulatory agencies	352:370	Regulatory agencies	352:370	Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars.
33205259	2	32	theme	biotherapeutics	297:311	arg1	glycosylation					280:292	glycosylation	280:292	glycosylation of biotherapeutics	280:311	As such, comprehensive information about glycosylation of biotherapeutics is critical to demonstrate similarity.
33205259	5	33	with	characterisation	792:807	arg1	emphasis					817:824	an emphasis	814:824	an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	814:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	34	theme	features	895:902	arg1	determination					864:876	determination	864:876	determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	864:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	35	from	overview	718:725	arg1	technologies					743:754	the MS-based technologies	730:754	the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content	730:984	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	36	theme	glycan	956:961	arg1	structure					963:971	glycan structure	956:971	glycan structure	956:971	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33205259	5	37	theme	acid	942:945	arg1	linkage					947:953	sialic acid linkage	935:953	sialic acid linkage	935:953	Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.
33222001	7	0	theme	core-fucosylated	1091:1106	arg1	glycan					1117:1122	a complex core-fucosylated N-linked glycan	1081:1122	a complex core-fucosylated N-linked glycan	1081:1122	Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM.
33222001	4	1	theme	single	657:662	arg1	section					671:677	a single tissue section	655:677	a single tissue section	655:677	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	5	2	dep	paraffin-embedded	764:780	arg1	FFPE					783:786	FFPE	783:786	FFPE	783:786	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	7	3	theme	primary	1163:1169	arg1	tumour					1171:1176	a primary tumour	1161:1176	a primary tumour with and without LNM	1161:1197	Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM.
33222001	8	4	theme	glycans	1253:1259	arg1	identification					1211:1224	Structural identification	1200:1224	Structural identification of these putative N-linked glycans	1200:1259	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	2	5	theme	laser	319:323	arg1	spectrometry					352:363	matrix-assisted laser desorption/ionization mass spectrometry	303:363	matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS)	303:374	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	2	5	theme	laser	319:323	arg1	MS					372:373	MALDI MS	366:373	MALDI MS	366:373	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	5	6	theme	EC	854:855	arg1	patients					857:864	eight EC patients	848:864	eight EC patients with lymph node metastasis (LNM)	848:897	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	9	7	theme	normal	1454:1459	arg1	regions					1461:1467	normal regions	1454:1467	normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28	1454:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	4	8	theme	N-linked	635:642	arg1	glycans					644:650	N-linked glycans	635:650	N-linked glycans	635:650	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	10	9	theme	N-linked	1598:1605	arg1	glycans					1607:1613	N-linked glycans	1598:1613	N-linked glycans	1598:1613	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	5	10	theme	N-glycan	699:706	arg1	MSI					714:716	N-glycan MALDI MSI	699:716	N-glycan MALDI MSI	699:716	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	8	11	theme	Structural	1200:1209	arg1	identification					1211:1224	Structural identification	1200:1224	Structural identification of these putative N-linked glycans	1200:1259	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	1	12	theme	vital	110:114	arg1	role					116:119	a vital role	108:119	a vital role	108:119	It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis.
33222001	7	13	gly	core-fucosylated	1091:1106	arg1	glycan					1117:1122	a complex core-fucosylated N-linked glycan	1081:1122	a complex core-fucosylated N-linked glycan	1081:1122	Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM.
33222001	8	14	theme	carbon	1300:1305	arg1	PGC-LC-MS/MS					1355:1366	PGC-LC-MS/MS	1355:1366	PGC-LC-MS/MS	1355:1366	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	8	14	theme	carbon	1300:1305	arg1	spectrometry					1341:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry	1281:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)	1281:1367	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	2	15	theme	spectrometry-based	201:218	arg1	techniques					220:229	Mass spectrometry-based techniques	196:229	Mass spectrometry-based techniques	196:229	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	9	16	theme	lower	1506:1510	arg1	abundance					1512:1520	lower abundance	1506:1520	lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28	1506:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	8	17	theme	chromatography	1314:1327	arg1	PGC-LC-MS/MS					1355:1366	PGC-LC-MS/MS	1355:1366	PGC-LC-MS/MS	1355:1366	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	8	17	theme	chromatography	1314:1327	arg1	spectrometry					1341:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry	1281:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)	1281:1367	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	11	18	theme	endometrial	1939:1949	arg1	cancer					1951:1956	endometrial cancer	1939:1956	endometrial cancer with LNM	1939:1965	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	4	19	link	N-linked	635:642	arg1	glycans					644:650	N-linked glycans	635:650	N-linked glycans	635:650	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	8	20	theme	mass	1336:1339	arg1	PGC-LC-MS/MS					1355:1366	PGC-LC-MS/MS	1355:1366	PGC-LC-MS/MS	1355:1366	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	8	20	theme	mass	1336:1339	arg1	spectrometry					1341:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry	1281:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)	1281:1367	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	11	21	with	endometrium	1910:1920	arg1	LNM					1963:1965	LNM	1963:1965	LNM	1963:1965	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	9	22	theme	N-linked	1533:1540	arg1	glycans					1542:1548	complex N-linked glycans	1525:1548	complex N-linked glycans with AUC ranges from 0.03-0.28	1525:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	6	23	theme	glycan	962:967	arg1	compositions					969:980	several putative N-linked glycan compositions	936:980	several putative N-linked glycan compositions	936:980	By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium.
33222001	0	24	from	glycosylation	17:29	arg1	cancer					46:51	endometrial cancer	34:51	endometrial cancer	34:51	Altered N-linked glycosylation in endometrial cancer.
33222001	9	25	with	glycans	1542:1548	arg1	ranges					1559:1564	AUC ranges	1555:1564	AUC ranges from 0.03-0.28	1555:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	11	26	from	cancer	1984:1989	arg1	endometrium					1910:1920	cancerous endometrium	1900:1920	cancerous endometrium from normal	1900:1932	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	11	26	from	cancer	1984:1989	arg1	cancer					1951:1956	endometrial cancer	1939:1956	endometrial cancer with LNM	1939:1965	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	5	27	theme	formalin-fixed	749:762	arg1	sections					796:803	six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections	721:803	six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections	721:803	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	5	28	theme	node	877:880	arg1	LNM					894:896	LNM	894:896	LNM	894:896	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	5	28	theme	node	877:880	arg1	metastasis					882:891	lymph node metastasis	871:891	lymph node metastasis (LNM)	871:897	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	6	29	theme	putative	944:951	arg1	compositions					969:980	several putative N-linked glycan compositions	936:980	several putative N-linked glycan compositions	936:980	By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium.
33222001	5	30	with	patients	857:864	arg1	LNM					894:896	LNM	894:896	LNM	894:896	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	5	30	with	patients	857:864	arg1	metastasis					882:891	lymph node metastasis	871:891	lymph node metastasis (LNM)	871:897	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	2	31	link	N-linked	267:274	arg1	glycans					276:282	N-linked glycans	267:282	N-linked glycans	267:282	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	11	32	used	used	1878:1881	arg2	MSI					1867:1869	N-linked glycan MALDI MSI	1845:1869	N-linked glycan MALDI MSI	1845:1869	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	10	33	theme	reduced	1672:1678	arg1	abundance					1680:1688	a reduced abundance	1670:1688	a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1670:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	10	34	gly	core-fucosylated	1703:1718	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	6	35	theme	cancerous	1045:1053	arg1	endometrium					1055:1065	cancerous endometrium	1045:1065	cancerous endometrium	1045:1065	By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium.
33222001	3	36	theme	MALDI	517:521	arg1	imaging					508:514	MALDI MS imaging	499:514	MALDI MS imaging (MALDI MSI)	499:526	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	3	36	theme	MALDI	517:521	arg1	MSI					523:525	MALDI MSI	517:525	MALDI MSI	517:525	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	11	37	theme	MALDI	1861:1865	arg1	MSI					1867:1869	N-linked glycan MALDI MSI	1845:1869	N-linked glycan MALDI MSI	1845:1869	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	0	38	theme	Altered	0:6	arg1	glycosylation					17:29	Altered N-linked glycosylation	0:29	Altered N-linked glycosylation in endometrial cancer	0:51	Altered N-linked glycosylation in endometrial cancer.
33222001	1	39	theme	surface	87:93	arg1	glycans					95:101	cell surface glycans	82:101	cell surface glycans	82:101	It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis.
33222001	4	40	theme	powerful	534:541	arg1	technique					543:551	This powerful technique	529:551	This powerful technique	529:551	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	10	41	theme	complex	1695:1701	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	5	42	theme	tissue	809:814	arg1	TMA					829:831	TMA	829:831	TMA	829:831	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	5	42	theme	tissue	809:814	arg1	microarrays					816:826	tissue microarrays	809:826	tissue microarrays (TMA)	809:832	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	1	43	theme	biological	124:133	arg1	processes					135:143	biological processes	124:143	biological processes	124:143	It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis.
33222001	10	44	theme	1+	1757:1758	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	11	45	theme	glycan	1854:1859	arg1	MSI					1867:1869	N-linked glycan MALDI MSI	1845:1869	N-linked glycan MALDI MSI	1845:1869	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	7	46	link	N-linked	1108:1115	arg1	glycan					1117:1122	a complex core-fucosylated N-linked glycan	1081:1122	a complex core-fucosylated N-linked glycan	1081:1122	Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM.
33222001	8	47	theme	putative	1235:1242	arg1	glycans					1253:1259	these putative N-linked glycans	1229:1259	these putative N-linked glycans	1229:1259	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	0	48	theme	endometrial	34:44	arg1	cancer					46:51	endometrial cancer	34:51	endometrial cancer	34:51	Altered N-linked glycosylation in endometrial cancer.
33222001	10	49	theme	primary	1779:1785	arg1	tumour					1787:1792	primary tumour	1779:1792	primary tumour with associated lymph node metastasis	1779:1830	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	2	50	theme	MALDI	366:370	arg1	spectrometry					352:363	matrix-assisted laser desorption/ionization mass spectrometry	303:363	matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS)	303:374	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	2	50	theme	MALDI	366:370	arg1	MS					372:373	MALDI MS	366:373	MALDI MS	366:373	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	9	51	link	N-linked	1533:1540	arg1	glycans					1542:1548	complex N-linked glycans	1525:1548	complex N-linked glycans with AUC ranges from 0.03-0.28	1525:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	10	52	theme	N-glycan	1720:1727	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	10	53	theme	lymph	1810:1814	arg1	node					1816:1819	associated lymph node	1799:1819	associated lymph node metastasis	1799:1830	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	10	54	theme	HexNAc	1736:1741	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	9	55	theme	oligomannose	1411:1422	arg1	glycans					1424:1430	oligomannose glycans	1411:1430	oligomannose glycans	1411:1430	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	4	56	theme	spatial	611:617	arg1	distribution					619:630	the spatial distribution	607:630	the spatial distribution of N-linked glycans on a single tissue section	607:677	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	7	57	theme	N-linked	1108:1115	arg1	glycan					1117:1122	a complex core-fucosylated N-linked glycan	1081:1122	a complex core-fucosylated N-linked glycan	1081:1122	Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM.
33222001	3	58	theme	MS	505:506	arg1	imaging					508:514	MALDI MS imaging	499:514	MALDI MS imaging (MALDI MSI)	499:526	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	3	58	theme	MS	505:506	arg1	MSI					523:525	MALDI MSI	517:525	MALDI MSI	517:525	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	7	59	theme	complex	1083:1089	arg1	glycan					1117:1122	a complex core-fucosylated N-linked glycan	1081:1122	a complex core-fucosylated N-linked glycan	1081:1122	Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM.
33222001	10	60	link	N-linked	1598:1605	arg1	glycans					1607:1613	N-linked glycans	1598:1613	N-linked glycans	1598:1613	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	10	61	theme	Deoxyhexose	1745:1755	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	10	62	theme	Man	1760:1762	arg1	GlcNAc					1766:1771	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	0	63	link	N-linked	8:15	arg1	glycosylation					17:29	Altered N-linked glycosylation	0:29	Altered N-linked glycosylation in endometrial cancer	0:51	Altered N-linked glycosylation in endometrial cancer.
33222001	9	64	theme	glycans	1542:1548	arg1	abundance					1512:1520	lower abundance	1506:1520	lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28	1506:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	9	64	theme	glycans	1542:1548	arg1	0.85-0.99					1491:1499	0.85-0.99	1491:1499	0.85-0.99	1491:1499	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	11	65	from	normal	1927:1932	arg1	endometrium					1910:1920	cancerous endometrium	1900:1920	cancerous endometrium from normal	1900:1932	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	11	65	from	normal	1927:1932	arg1	cancer					1951:1956	endometrial cancer	1939:1956	endometrial cancer with LNM	1939:1965	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	10	66	theme	Hex	1730:1732	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	1	67	theme	altered	155:161	arg1	form					163:166	their altered form	149:166	their altered form	149:166	It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis.
33222001	11	68	with	cancer	1951:1956	arg1	LNM					1963:1965	LNM	1963:1965	LNM	1963:1965	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	3	69	link	N-linked	429:436	arg1	glycans					438:444	N-linked glycans	429:444	N-linked glycans directly from cancer tissue	429:472	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	10	70	theme	primary	1623:1629	arg1	tumours					1631:1637	primary tumours	1623:1637	primary tumours with and without LNM	1623:1658	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	2	71	theme	desorption/ionization	325:345	arg1	spectrometry					352:363	matrix-assisted laser desorption/ionization mass spectrometry	303:363	matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS)	303:374	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	2	71	theme	desorption/ionization	325:345	arg1	MS					372:373	MALDI MS	366:373	MALDI MS	366:373	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	11	72	link	N-linked	1845:1852	arg1	MSI					1867:1869	N-linked glycan MALDI MSI	1845:1869	N-linked glycan MALDI MSI	1845:1869	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	8	73	theme	N-linked	1244:1251	arg1	glycans					1253:1259	these putative N-linked glycans	1229:1259	these putative N-linked glycans	1229:1259	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	10	74	theme	glycans	1607:1613	arg1	comparison					1584:1593	A comparison	1582:1593	A comparison of N-linked glycans between primary tumours with and without LNM	1582:1658	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	2	75	theme	matrix-assisted	303:317	arg1	spectrometry					352:363	matrix-assisted laser desorption/ionization mass spectrometry	303:363	matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS)	303:374	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	2	75	theme	matrix-assisted	303:317	arg1	MS					372:373	MALDI MS	366:373	MALDI MS	366:373	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	11	76	theme	endometrial	1972:1982	arg1	cancer					1984:1989	endometrial cancer	1972:1989	endometrial cancer without	1972:1997	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	5	77	dep	formalin-fixed	749:762	arg1	paraffin-embedded					764:780	paraffin-embedded	764:780	paraffin-embedded	764:780	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	5	78	theme	MALDI	708:712	arg1	MSI					714:716	N-glycan MALDI MSI	699:716	N-glycan MALDI MSI	699:716	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	10	79	theme	GlcNAc	1766:1771	arg1	abundance					1680:1688	a reduced abundance	1670:1688	a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1670:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	4	80	theme	tissue	664:669	arg1	section					671:677	a single tissue section	655:677	a single tissue section	655:677	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	8	81	theme	porous	1281:1286	arg1	PGC-LC-MS/MS					1355:1366	PGC-LC-MS/MS	1355:1366	PGC-LC-MS/MS	1355:1366	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	8	81	theme	porous	1281:1286	arg1	spectrometry					1341:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry	1281:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)	1281:1367	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	4	82	theme	glycans	644:650	arg1	distribution					619:630	the spatial distribution	607:630	the spatial distribution of N-linked glycans on a single tissue section	607:677	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	8	83	theme	graphitized	1288:1298	arg1	PGC-LC-MS/MS					1355:1366	PGC-LC-MS/MS	1355:1366	PGC-LC-MS/MS	1355:1366	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	8	83	theme	graphitized	1288:1298	arg1	spectrometry					1341:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry	1281:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)	1281:1367	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	2	84	theme	N-linked	267:274	arg1	glycans					276:282	N-linked glycans	267:282	N-linked glycans	267:282	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	6	85	link	N-linked	953:960	arg1	compositions					969:980	several putative N-linked glycan compositions	936:980	several putative N-linked glycan compositions	936:980	By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium.
33222001	8	86	theme	liquid	1307:1312	arg1	PGC-LC-MS/MS					1355:1366	PGC-LC-MS/MS	1355:1366	PGC-LC-MS/MS	1355:1366	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	8	86	theme	liquid	1307:1312	arg1	spectrometry					1341:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry	1281:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)	1281:1367	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	4	87	from	distribution	619:630	arg1	section					671:677	a single tissue section	655:677	a single tissue section	655:677	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	11	88	theme	cancerous	1900:1908	arg1	endometrium					1910:1920	cancerous endometrium	1900:1920	cancerous endometrium from normal	1900:1932	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	9	89	theme	complex	1525:1531	arg1	glycans					1542:1548	complex N-linked glycans	1525:1548	complex N-linked glycans with AUC ranges from 0.03-0.28	1525:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	8	90	theme	tandem	1329:1334	arg1	PGC-LC-MS/MS					1355:1366	PGC-LC-MS/MS	1355:1366	PGC-LC-MS/MS	1355:1366	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	8	90	theme	tandem	1329:1334	arg1	spectrometry					1341:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry	1281:1352	porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)	1281:1367	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	5	91	theme	lymph	871:875	arg1	LNM					894:896	LNM	894:896	LNM	894:896	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	5	91	theme	lymph	871:875	arg1	metastasis					882:891	lymph node metastasis	871:891	lymph node metastasis (LNM)	871:897	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	9	92	from	0.03-0.28	1571:1579	arg1	ranges					1559:1564	AUC ranges	1555:1564	AUC ranges from 0.03-0.28	1555:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	6	93	theme	N-linked	953:960	arg1	compositions					969:980	several putative N-linked glycan compositions	936:980	several putative N-linked glycan compositions	936:980	By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium.
33222001	9	94	theme	AUC	1555:1557	arg1	ranges					1559:1564	AUC ranges	1555:1564	AUC ranges from 0.03-0.28	1555:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	6	95	theme	several	936:942	arg1	compositions					969:980	several putative N-linked glycan compositions	936:980	several putative N-linked glycan compositions	936:980	By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium.
33222001	10	96	theme	core-fucosylated	1703:1718	arg1	Man					1760:1762	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3	1693:1764	a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2	1693:1773	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	5	97	theme	endometrial	725:735	arg1	sections					796:803	six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections	721:803	six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections	721:803	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	11	98	theme	N-linked	1845:1852	arg1	MSI					1867:1869	N-linked glycan MALDI MSI	1845:1869	N-linked glycan MALDI MSI	1845:1869	In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
33222001	5	99	theme	tissue	789:794	arg1	sections					796:803	six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections	721:803	six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections	721:803	Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM.
33222001	1	100	theme	cell	82:85	arg1	glycans					95:101	cell surface glycans	82:101	cell surface glycans	82:101	It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis.
33222001	3	101	theme	N-linked	429:436	arg1	glycans					438:444	N-linked glycans	429:444	N-linked glycans directly from cancer tissue	429:472	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	3	102	theme	MALDI	391:395	arg1	MS					397:398	MALDI MS	391:398	MALDI MS	391:398	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	4	103	theme	mass	562:565	arg1	spectrometry					567:578	mass spectrometry	562:578	mass spectrometry	562:578	This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section.
33222001	10	104	theme	associated	1799:1808	arg1	node					1816:1819	associated lymph node	1799:1819	associated lymph node metastasis	1799:1830	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	8	105	link	N-linked	1244:1251	arg1	glycans					1253:1259	these putative N-linked glycans	1229:1259	these putative N-linked glycans	1229:1259	Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).
33222001	3	106	theme	cancer	460:465	arg1	tissue					467:472	cancer tissue	460:472	cancer tissue	460:472	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	3	107	used	used	407:410	arg2	MS					397:398	MALDI MS	391:398	MALDI MS	391:398	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	0	108	gly	glycosylation	17:29	arg1	cancer					46:51	endometrial cancer	34:51	endometrial cancer	34:51	Altered N-linked glycosylation in endometrial cancer.
33222001	10	109	with	tumour	1787:1792	arg1	metastasis					1821:1830	associated lymph node metastasis	1799:1830	associated lymph node metastasis	1799:1830	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	2	110	theme	Mass	196:199	arg1	techniques					220:229	Mass spectrometry-based techniques	196:229	Mass spectrometry-based techniques	196:229	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	3	111	from	tissue	467:472	arg1	glycans					438:444	N-linked glycans	429:444	N-linked glycans directly from cancer tissue	429:472	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	3	112	theme	MALDI	499:503	arg1	MS					505:506	MALDI MS	499:506	MALDI MS imaging (MALDI MSI)	499:526	Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI).
33222001	9	113	theme	higher	1391:1396	arg1	abundance					1398:1406	higher abundance	1391:1406	higher abundance of oligomannose glycans in tumour	1391:1440	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	9	114	from	abundance	1398:1406	arg1	tumour					1435:1440	tumour	1435:1440	tumour	1435:1440	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	9	115	with	regions	1461:1467	arg1	AUC					1474:1476	AUC	1474:1476	AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28	1474:1579	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
33222001	10	116	theme	node	1816:1819	arg1	metastasis					1821:1830	associated lymph node metastasis	1799:1830	associated lymph node metastasis	1799:1830	A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis.
33222001	2	117	theme	mass	347:350	arg1	spectrometry					352:363	matrix-assisted laser desorption/ionization mass spectrometry	303:363	matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS)	303:374	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	2	117	theme	mass	347:350	arg1	MS					372:373	MALDI MS	366:373	MALDI MS	366:373	Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS).
33222001	0	118	theme	N-linked	8:15	arg1	glycosylation					17:29	Altered N-linked glycosylation	0:29	Altered N-linked glycosylation in endometrial cancer	0:51	Altered N-linked glycosylation in endometrial cancer.
33222001	9	119	theme	glycans	1424:1430	arg1	abundance					1398:1406	higher abundance	1391:1406	higher abundance of oligomannose glycans in tumour	1391:1440	Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28.
34687021	3	0	theme	monoclonal	364:373	arg1	antibodies					375:384	the monoclonal antibodies	360:384	the monoclonal antibodies on the market	360:398	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	5	1	theme	glycosylation	841:853	arg1	role					828:831	the role	824:831	the role of IgG1 glycosylation	824:853	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	6	2	dep	immunoglobulins	1081:1095	arg1	immunoglobulins					1081:1095	human immunoglobulins	1075:1095	human immunoglobulins (IgA, IgD, IgE, and IgM)	1075:1120	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	2	dep	immunoglobulins	1081:1095	arg1	IgE					1108:1110	IgE	1108:1110	IgE	1108:1110	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	2	dep	immunoglobulins	1081:1095	arg1	IgM					1117:1119	IgM	1117:1119	IgM	1117:1119	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	2	dep	immunoglobulins	1081:1095	arg1	IgD					1103:1105	IgD	1103:1105	IgD	1103:1105	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	2	dep	immunoglobulins	1081:1095	arg1	IgA					1098:1100	IgA	1098:1100	IgA	1098:1100	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	8	3	gly	glycosylation	1302:1314	arg1	antibodies					1345:1354	plant-produced monoclonal antibodies	1319:1354	plant-produced monoclonal antibodies	1319:1354	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	7	4	theme	antibody	1149:1156	arg1	classes					1158:1164	all these antibody classes	1139:1164	all these antibody classes	1139:1164	Except for IgD, all these antibody classes have been expressed in plants and the glycosylation has been analyzed in a site-specific manner.
34687021	3	5	theme	glycosylation	575:587	arg1	engineering					560:570	precise engineering	552:570	precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity	552:645	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	1	6	theme	protein-based	77:89	arg1	therapeutics					91:102	Many economically important protein-based therapeutics	49:102	Many economically important protein-based therapeutics like monoclonal antibodies	49:129	Many economically important protein-based therapeutics like monoclonal antibodies are glycosylated.
34687021	8	7	theme	known	1397:1401	arg1	functions					1403:1411	known functions	1397:1411	known functions for these glycans	1397:1429	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	4	8	theme	effective	674:682	arg1	antibodies					684:693	more effective antibodies	669:693	more effective antibodies	669:693	Apart from producing more effective antibodies, pure glycoforms are required in efforts to link biological functions to specific glycan structures.
34687021	2	9	theme	type	190:193	arg1	importance					171:180	the recognized importance	156:180	the recognized importance of this type of posttranslational modification	156:227	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	6	10	theme	other	1053:1057	arg1	classes					1064:1070	the other four classes	1049:1070	the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM)	1049:1120	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	11	theme	little	962:967	arg1	attention					969:977	little attention	962:977	little attention	962:977	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	2	12	theme	emerging	327:334	arg1	field					336:340	an emerging field	324:340	an emerging field	324:340	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	2	12	theme	emerging	327:334	arg1	glycoengineering					230:245	glycoengineering	230:245	glycoengineering of expression systems to obtain highly active and homogenous therapeutics	230:319	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	3	13	theme	alternative	480:490	arg1	platform					531:538	an alternative cost-effective and scalable production platform	477:538	an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity	477:645	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	1	14	gly	glycosylated	135:146	arg1	therapeutics					91:102	Many economically important protein-based therapeutics	49:102	Many economically important protein-based therapeutics like monoclonal antibodies	49:129	Many economically important protein-based therapeutics like monoclonal antibodies are glycosylated.
34687021	8	15	theme	antibodies	1345:1354	arg1	glycosylation					1302:1314	glycosylation	1302:1314	glycosylation of plant-produced monoclonal antibodies	1302:1354	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	1	16	theme	monoclonal	109:118	arg1	antibodies					120:129	monoclonal antibodies	109:129	monoclonal antibodies	109:129	Many economically important protein-based therapeutics like monoclonal antibodies are glycosylated.
34687021	3	17	theme	cost-effective	492:505	arg1	platform					531:538	an alternative cost-effective and scalable production platform	477:538	an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity	477:645	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	3	18	theme	expression	432:441	arg1	platforms					443:451	mammalian expression platforms	422:451	mammalian expression platforms	422:451	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	5	19	theme	dominant	886:893	arg1	class					873:877	this antibody class	859:877	this antibody class	859:877	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	5	19	theme	dominant	886:893	arg1	format					907:912	the dominant recombinant format	882:912	the dominant recombinant format that has been expressed in plants	882:946	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	4	20	theme	biological	744:753	arg1	functions					755:763	biological functions	744:763	biological functions	744:763	Apart from producing more effective antibodies, pure glycoforms are required in efforts to link biological functions to specific glycan structures.
34687021	0	21	theme	Immunoglobulins	32:46	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation of Plant-Produced Immunoglobulins.	0:47	Glycosylation of Plant-Produced Immunoglobulins.
34687021	4	22	dep	link	739:742	arg1	efforts					728:734	efforts	728:734	efforts	728:734	Apart from producing more effective antibodies, pure glycoforms are required in efforts to link biological functions to specific glycan structures.
34687021	3	23	theme	large	629:633	arg1	homogeneity					635:645	large homogeneity	629:645	large homogeneity	629:645	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	2	24	theme	active	286:291	arg1	therapeutics					308:319	highly active and homogenous therapeutics	279:319	highly active and homogenous therapeutics	279:319	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	3	25	theme	production	520:529	arg1	platform					531:538	an alternative cost-effective and scalable production platform	477:538	an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity	477:645	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	3	26	theme	mammalian	422:430	arg1	platforms					443:451	mammalian expression platforms	422:451	mammalian expression platforms	422:451	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	6	27	theme	subtypes	1036:1043	arg1	classes					1064:1070	the other four classes	1049:1070	the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM)	1049:1120	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	27	theme	subtypes	1036:1043	arg1	glycoengineering					1000:1015	the glycoengineering	996:1015	the glycoengineering of recombinant IgG subtypes	996:1043	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	3	28	theme	targeted	600:607	arg1	glycoforms					615:624	targeted human glycoforms	600:624	targeted human glycoforms	600:624	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	6	29	theme	human	1075:1079	arg1	immunoglobulins					1081:1095	human immunoglobulins	1075:1095	human immunoglobulins (IgA, IgD, IgE, and IgM)	1075:1120	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	29	theme	human	1075:1079	arg1	IgE					1108:1110	IgE	1108:1110	IgE	1108:1110	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	29	theme	human	1075:1079	arg1	IgM					1117:1119	IgM	1117:1119	IgM	1117:1119	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	29	theme	human	1075:1079	arg1	IgD					1103:1105	IgD	1103:1105	IgD	1103:1105	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	29	theme	human	1075:1079	arg1	IgA					1098:1100	IgA	1098:1100	IgA	1098:1100	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	4	30	theme	glycan	777:782	arg1	structures					784:793	specific glycan structures	768:793	specific glycan structures	768:793	Apart from producing more effective antibodies, pure glycoforms are required in efforts to link biological functions to specific glycan structures.
34687021	7	31	gly	glycosylation	1204:1216	arg1	manner					1255:1260	a site-specific manner	1239:1260	a site-specific manner	1239:1260	Except for IgD, all these antibody classes have been expressed in plants and the glycosylation has been analyzed in a site-specific manner.
34687021	6	32	theme	IgG	1032:1034	arg1	subtypes					1036:1043	recombinant IgG subtypes	1020:1043	recombinant IgG subtypes	1020:1043	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	2	33	theme	modification	216:227	arg1	type					190:193	this type	185:193	this type of posttranslational modification	185:227	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	0	34	gly	Glycosylation	0:12	arg1	Immunoglobulins					32:46	Plant-Produced Immunoglobulins	17:46	Plant-Produced Immunoglobulins	17:46	Glycosylation of Plant-Produced Immunoglobulins.
34687021	0	35	theme	Plant-Produced	17:30	arg1	Immunoglobulins					32:46	Plant-Produced Immunoglobulins	17:46	Plant-Produced Immunoglobulins	17:46	Glycosylation of Plant-Produced Immunoglobulins.
34687021	6	36	theme	recombinant	1020:1030	arg1	subtypes					1036:1043	recombinant IgG subtypes	1020:1043	recombinant IgG subtypes	1020:1043	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	5	37	theme	antibody	864:871	arg1	class					873:877	this antibody class	859:877	this antibody class	859:877	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	5	37	theme	antibody	864:871	arg1	format					907:912	the dominant recombinant format	882:912	the dominant recombinant format that has been expressed in plants	882:946	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	2	38	theme	posttranslational	198:214	arg1	modification					216:227	posttranslational modification	198:227	posttranslational modification	198:227	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	5	39	theme	recombinant	895:905	arg1	class					873:877	this antibody class	859:877	this antibody class	859:877	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	5	39	theme	recombinant	895:905	arg1	format					907:912	the dominant recombinant format	882:912	the dominant recombinant format that has been expressed in plants	882:946	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	3	40	theme	scalable	511:518	arg1	platform					531:538	an alternative cost-effective and scalable production platform	477:538	an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity	477:645	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	3	41	theme	precise	552:558	arg1	engineering					560:570	precise engineering	552:570	precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity	552:645	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	2	42	theme	systems	261:267	arg1	field					336:340	an emerging field	324:340	an emerging field	324:340	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	2	42	theme	systems	261:267	arg1	glycoengineering					230:245	glycoengineering	230:245	glycoengineering of expression systems to obtain highly active and homogenous therapeutics	230:319	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	3	43	from	antibodies	375:384	arg1	market					393:398	the market	389:398	the market	389:398	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	2	44	theme	expression	250:259	arg1	systems					261:267	expression systems	250:267	expression systems	250:267	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	8	45	theme	plant-produced	1319:1332	arg1	antibodies					1345:1354	plant-produced monoclonal antibodies	1319:1354	plant-produced monoclonal antibodies	1319:1354	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	8	46	theme	functions	1403:1411	arg1	light					1388:1392	the light	1384:1392	the light of known functions for these glycans	1384:1429	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	3	47	theme	human	609:613	arg1	glycoforms					615:624	targeted human glycoforms	600:624	targeted human glycoforms	600:624	Although most of the monoclonal antibodies on the market are still produced in mammalian expression platforms, plants are emerging as an alternative cost-effective and scalable production platform that allows precise engineering of glycosylation to produce targeted human glycoforms at large homogeneity.
34687021	1	48	theme	Many	49:52	arg1	therapeutics					91:102	Many economically important protein-based therapeutics	49:102	Many economically important protein-based therapeutics like monoclonal antibodies	49:129	Many economically important protein-based therapeutics like monoclonal antibodies are glycosylated.
34687021	8	49	from	data	1294:1297	arg1	glycosylation					1302:1314	glycosylation	1302:1314	glycosylation of plant-produced monoclonal antibodies	1302:1354	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	8	50	from	findings	1372:1379	arg1	light					1388:1392	the light	1384:1392	the light of known functions for these glycans	1384:1429	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	7	51	theme	site-specific	1241:1253	arg1	manner					1255:1260	a site-specific manner	1239:1260	a site-specific manner	1239:1260	Except for IgD, all these antibody classes have been expressed in plants and the glycosylation has been analyzed in a site-specific manner.
34687021	8	52	theme	current	1286:1292	arg1	data					1294:1297	the current data	1282:1297	the current data on glycosylation of plant-produced monoclonal antibodies	1282:1354	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	2	53	theme	homogenous	297:306	arg1	therapeutics					308:319	highly active and homogenous therapeutics	279:319	highly active and homogenous therapeutics	279:319	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	4	54	theme	specific	768:775	arg1	structures					784:793	specific glycan structures	768:793	specific glycan structures	768:793	Apart from producing more effective antibodies, pure glycoforms are required in efforts to link biological functions to specific glycan structures.
34687021	6	55	theme	immunoglobulins	1081:1095	arg1	classes					1064:1070	the other four classes	1049:1070	the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM)	1049:1120	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	6	55	theme	immunoglobulins	1081:1095	arg1	glycoengineering					1000:1015	the glycoengineering	996:1015	the glycoengineering of recombinant IgG subtypes	996:1043	By contrast, little attention has been paid to the glycoengineering of recombinant IgG subtypes and the other four classes of human immunoglobulins (IgA, IgD, IgE, and IgM).
34687021	5	56	theme	IgG1	836:839	arg1	glycosylation					841:853	IgG1 glycosylation	836:853	IgG1 glycosylation	836:853	Much is already known about the role of IgG1 glycosylation and this antibody class is the dominant recombinant format that has been expressed in plants.
34687021	2	57	theme	recognized	160:169	arg1	importance					171:180	the recognized importance	156:180	the recognized importance of this type of posttranslational modification	156:227	Due to the recognized importance of this type of posttranslational modification, glycoengineering of expression systems to obtain highly active and homogenous therapeutics is an emerging field.
34687021	1	58	theme	important	67:75	arg1	therapeutics					91:102	Many economically important protein-based therapeutics	49:102	Many economically important protein-based therapeutics like monoclonal antibodies	49:129	Many economically important protein-based therapeutics like monoclonal antibodies are glycosylated.
34687021	8	59	theme	monoclonal	1334:1343	arg1	antibodies					1345:1354	plant-produced monoclonal antibodies	1319:1354	plant-produced monoclonal antibodies	1319:1354	Here, we summarize the current data on glycosylation of plant-produced monoclonal antibodies and discuss the findings in the light of known functions for these glycans.
34687021	4	60	theme	pure	696:699	arg1	glycoforms					701:710	pure glycoforms	696:710	pure glycoforms	696:710	Apart from producing more effective antibodies, pure glycoforms are required in efforts to link biological functions to specific glycan structures.
34212152	1	0	theme	sequential	165:174	arg1	hallmark					73:80	A hallmark	71:80	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells	71:156	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	1	0	theme	sequential	165:174	arg1	remodeling					176:185	the sequential remodeling	161:185	the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins	161:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	1	1	theme	glycostructures	273:287	arg1	ensemble					261:268	a site-specific, heterogeneous ensemble	230:268	a site-specific, heterogeneous ensemble of glycostructures on mature proteins	230:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	2	2	theme	different	548:556	arg1	enzymes					576:582	four different glycan processing enzymes	543:582	four different glycan processing enzymes	543:582	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	4	3	theme	PDI	885:887	arg1	structure					855:863	the tertiary structure	842:863	the tertiary structure of the glycoprotein PDI	842:887	In addition, altering the tertiary structure of the glycoprotein PDI affected its N-glycan remodeling in a site-specific way.
34212152	3	4	attach	derived	680:686	arg1	simulations					700:710	the MD simulations	693:710	the MD simulations	693:710	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	3	4	attach	derived	680:686	arg2	enzymes					672:678	their processing enzymes	655:678	their processing enzymes derived from the MD simulations	655:710	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	3	5	theme	MD	697:698	arg1	simulations					700:710	the MD simulations	693:710	the MD simulations	693:710	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	2	6	gly	glycosylation	418:430	arg2	sites					432:436	five glycosylation sites	413:436	five glycosylation sites	413:436	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	6	gly	glycosylation	418:430	arg2	five					413:416	five	413:416	five	413:416	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	7	theme	site-specific	323:335	arg1	processing					337:346	site-specific processing	323:346	site-specific processing	323:346	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	1	8	from	hallmark	73:80	arg1	compartments					125:136	the secretory compartments	111:136	the secretory compartments of eukaryotic cells	111:156	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	1	9	theme	mature	292:297	arg1	proteins					299:306	mature proteins	292:306	mature proteins	292:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	1	10	link	N-linked	85:92	arg1	glycosylation					94:106	N-linked glycosylation	85:106	N-linked glycosylation	85:106	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	3	11	theme	different	726:734	arg1	sites					750:754	different glycosylation sites	726:754	different glycosylation sites	726:754	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	2	12	theme	protein	357:363	arg1	isomerase					375:383	protein disulfide isomerase	357:383	protein disulfide isomerase (PDI)	357:389	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	12	theme	protein	357:363	arg1	protein					400:406	a model protein	392:406	a model protein with five glycosylation sites	392:436	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	12	theme	protein	357:363	arg1	PDI					386:388	PDI	386:388	PDI	386:388	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	13	theme	in	520:521	arg1	analysis					529:536	a biochemical in vitro analysis	506:536	a biochemical in vitro analysis with four different glycan processing enzymes	506:582	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	3	14	theme	glycosylation	736:748	arg1	sites					750:754	different glycosylation sites	726:754	different glycosylation sites	726:754	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	3	15	from	sites	750:754	arg1	N-glycans					713:721	N-glycans	713:721	N-glycans at different glycosylation sites	713:754	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	2	16	theme	biochemical	508:518	arg1	analysis					529:536	a biochemical in vitro analysis	506:536	a biochemical in vitro analysis with four different glycan processing enzymes	506:582	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	5	17	theme	processing	1154:1163	arg1	pathways					1165:1172	kinetically controlled processing pathways	1131:1172	kinetically controlled processing pathways	1131:1172	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	1	18	theme	N-linked	85:92	arg1	glycosylation					94:106	N-linked glycosylation	85:106	N-linked glycosylation	85:106	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	5	19	theme	surrounding	1024:1034	arg1	structure					1053:1061	the surrounding protein tertiary structure	1020:1061	the surrounding protein tertiary structure	1020:1061	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	4	20	theme	glycoprotein	872:883	arg1	PDI					885:887	the glycoprotein PDI	868:887	the glycoprotein PDI	868:887	In addition, altering the tertiary structure of the glycoprotein PDI affected its N-glycan remodeling in a site-specific way.
34212152	3	21	theme	different	763:771	arg1	properties					781:790	different kinetic properties	763:790	different kinetic properties for the processing enzymes	763:817	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	1	22	theme	glycosylation	94:106	arg1	hallmark					73:80	A hallmark	71:80	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells	71:156	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	1	22	theme	glycosylation	94:106	arg1	remodeling					176:185	the sequential remodeling	161:185	the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins	161:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	5	23	theme	controlled	1143:1152	arg1	pathways					1165:1172	kinetically controlled processing pathways	1131:1172	kinetically controlled processing pathways	1131:1172	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	0	24	theme	Glycan-protein	0:13	arg1	interactions					15:26	Glycan-protein interactions	0:26	Glycan-protein interactions	0:26	Glycan-protein interactions determine kinetics of N-glycan remodeling.
34212152	3	25	gly	glycosylation	736:748	arg2	sites					750:754	different glycosylation sites	726:754	different glycosylation sites	726:754	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	2	26	with	analysis	529:536	arg1	enzymes					576:582	four different glycan processing enzymes	543:582	four different glycan processing enzymes	543:582	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	1	27	theme	uniform	203:209	arg1	oligosaccharide					211:225	an initially uniform oligosaccharide	190:225	an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins	190:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	2	28	theme	dynamics	453:460	arg1	simulations					467:477	molecular dynamics (MD) simulations	443:477	molecular dynamics (MD) simulations	443:477	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	3	29	theme	kinetic	773:779	arg1	properties					781:790	different kinetic properties	763:790	different kinetic properties for the processing enzymes	763:817	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	2	30	theme	glycan	558:563	arg1	enzymes					576:582	four different glycan processing enzymes	543:582	four different glycan processing enzymes	543:582	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	5	31	theme	observed	966:973	arg1	reactivities					997:1008	the observed differential N-glycan reactivities	962:1008	the observed differential N-glycan reactivities	962:1008	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	1	32	theme	oligosaccharide	211:225	arg1	hallmark					73:80	A hallmark	71:80	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells	71:156	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	1	32	theme	oligosaccharide	211:225	arg1	remodeling					176:185	the sequential remodeling	161:185	the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins	161:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	2	33	theme	molecular	443:451	arg1	MD					463:464	MD	463:464	MD	463:464	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	33	theme	molecular	443:451	arg1	dynamics					453:460	molecular dynamics	443:460	molecular dynamics (MD) simulations	443:477	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	1	34	from	proteins	299:306	arg1	ensemble					261:268	a site-specific, heterogeneous ensemble	230:268	a site-specific, heterogeneous ensemble of glycostructures on mature proteins	230:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	4	35	gly	glycoprotein	872:883	arg1	glycoprotein					872:883	the glycoprotein PDI	868:887	the glycoprotein PDI	868:887	In addition, altering the tertiary structure of the glycoprotein PDI affected its N-glycan remodeling in a site-specific way.
34212152	1	36	theme	secretory	115:123	arg1	compartments					125:136	the secretory compartments	111:136	the secretory compartments of eukaryotic cells	111:156	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	0	37	theme	N-glycan	50:57	arg1	remodeling					59:68	N-glycan remodeling	50:68	N-glycan remodeling	50:68	Glycan-protein interactions determine kinetics of N-glycan remodeling.
34212152	5	38	theme	N-glycan	988:995	arg1	reactivities					997:1008	the observed differential N-glycan reactivities	962:1008	the observed differential N-glycan reactivities	962:1008	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	1	39	from	glycostructures	273:287	arg1	proteins					299:306	mature proteins	292:306	mature proteins	292:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	5	40	theme	same	1110:1113	arg1	protein					1115:1121	the same protein	1106:1121	the same protein	1106:1121	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	2	41	theme	model	394:398	arg1	isomerase					375:383	protein disulfide isomerase	357:383	protein disulfide isomerase (PDI)	357:389	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	41	theme	model	394:398	arg1	protein					400:406	a model protein	392:406	a model protein with five glycosylation sites	392:436	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	1	42	theme	site-specific	232:244	arg1	ensemble					261:268	a site-specific, heterogeneous ensemble	230:268	a site-specific, heterogeneous ensemble of glycostructures on mature proteins	230:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	3	43	theme	processing	800:809	arg1	enzymes					811:817	the processing enzymes	796:817	the processing enzymes	796:817	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	1	44	from	ensemble	261:268	arg1	proteins					299:306	mature proteins	292:306	mature proteins	292:306	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	3	45	theme	N-glycans	641:649	arg1	accessibility					620:632	the accessibility	616:632	the accessibility of the N-glycans for their processing enzymes derived from the MD simulations	616:710	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	4	46	theme	tertiary	846:853	arg1	structure					855:863	the tertiary structure	842:863	the tertiary structure of the glycoprotein PDI	842:887	In addition, altering the tertiary structure of the glycoprotein PDI affected its N-glycan remodeling in a site-specific way.
34212152	0	47	theme	remodeling	59:68	arg1	kinetics					38:45	kinetics	38:45	kinetics of N-glycan remodeling	38:68	Glycan-protein interactions determine kinetics of N-glycan remodeling.
34212152	2	48	dep	in	520:521	arg1	vitro					523:527	vitro	523:527	vitro	523:527	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	5	49	theme	different	1075:1083	arg1	structures					1092:1101	different glycan structures	1075:1101	different glycan structures in the same protein	1075:1121	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	4	50	theme	N-glycan	902:909	arg1	remodeling					911:920	its N-glycan remodeling	898:920	its N-glycan remodeling	898:920	In addition, altering the tertiary structure of the glycoprotein PDI affected its N-glycan remodeling in a site-specific way.
34212152	4	51	theme	site-specific	927:939	arg1	way					941:943	a site-specific way	925:943	a site-specific way	925:943	In addition, altering the tertiary structure of the glycoprotein PDI affected its N-glycan remodeling in a site-specific way.
34212152	5	52	theme	glycan	1085:1090	arg1	structures					1092:1101	different glycan structures	1075:1101	different glycan structures in the same protein	1075:1121	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	3	53	theme	accessibility	620:632	arg1	analysis					604:611	an analysis	601:611	an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations	601:710	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	1	54	theme	eukaryotic	141:150	arg1	cells					152:156	eukaryotic cells	141:156	eukaryotic cells	141:156	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	2	55	theme	processing	565:574	arg1	enzymes					576:582	four different glycan processing enzymes	543:582	four different glycan processing enzymes	543:582	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	3	56	theme	processing	661:670	arg1	enzymes					672:678	their processing enzymes	655:678	their processing enzymes derived from the MD simulations	655:710	As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes.
34212152	1	57	dep	site-specific	232:244	arg1	heterogeneous					247:259	heterogeneous	247:259	heterogeneous	247:259	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	1	58	theme	cells	152:156	arg1	compartments					125:136	the secretory compartments	111:136	the secretory compartments of eukaryotic cells	111:156	A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins.
34212152	2	59	theme	disulfide	365:373	arg1	isomerase					375:383	protein disulfide isomerase	357:383	protein disulfide isomerase (PDI)	357:389	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	59	theme	disulfide	365:373	arg1	protein					400:406	a model protein	392:406	a model protein with five glycosylation sites	392:436	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	59	theme	disulfide	365:373	arg1	PDI					386:388	PDI	386:388	PDI	386:388	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	5	60	from	structures	1092:1101	arg1	protein					1115:1121	the same protein	1106:1121	the same protein	1106:1121	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	2	61	theme	glycosylation	418:430	arg1	sites					432:436	five glycosylation sites	413:436	five glycosylation sites	413:436	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	5	62	theme	protein	1036:1042	arg1	structure					1053:1061	the surrounding protein tertiary structure	1020:1061	the surrounding protein tertiary structure	1020:1061	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	5	63	theme	differential	975:986	arg1	reactivities					997:1008	the observed differential N-glycan reactivities	962:1008	the observed differential N-glycan reactivities	962:1008	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
34212152	2	64	used	used	352:355	arg2	we					349:350	we	349:350	we	349:350	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	2	65	with	protein	400:406	arg1	sites					432:436	five glycosylation sites	413:436	five glycosylation sites	413:436	To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes.
34212152	5	66	theme	tertiary	1044:1051	arg1	structure					1053:1061	the surrounding protein tertiary structure	1020:1061	the surrounding protein tertiary structure	1020:1061	We propose that the observed differential N-glycan reactivities depend on the surrounding protein tertiary structure and lead to different glycan structures in the same protein through kinetically controlled processing pathways.
33073996	6	0	theme	glycan-glycan	996:1008	arg1	interactions					1010:1021	glycan-glycan interactions	996:1021	glycan-glycan interactions	996:1021	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	5	1	theme	polyLacNAc	821:830	arg1	structures					832:841	the polyLacNAc structures	817:841	the polyLacNAc structures	817:841	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	2	2	theme	NXS/T	340:344	arg1	sequons					346:352	its four NXS/T sequons	331:352	its four NXS/T sequons	331:352	N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons.
33073996	8	3	contain	carries	1282:1288	arg3	conclusion					1212:1221	conclusion	1212:1221	conclusion	1212:1221	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	8	3	contain	carries	1282:1288	arg3	sequon					1328:1333	the N219 sequon	1319:1333	the N219 sequon	1319:1333	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	8	3	contain	carries	1282:1288	arg3	likely					1400:1405	likely	1400:1405	likely	1400:1405	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	8	3	contain	carries	1282:1288	arg1	PD-L1					1224:1228	PD-L1	1224:1228	PD-L1 expressed in the MDA-MB-231 breast cancer cell line	1224:1280	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	8	3	contain	carries	1282:1288	arg2	glycans					1301:1307	polyLacNAc glycans	1290:1307	polyLacNAc glycans	1290:1307	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	0	4	from	Glycosylation	6:18	arg1	Binding					38:44	Binding	38:44	Binding to Clinical Antibodies	38:67	PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.
33073996	1	5	theme	immune	148:153	arg1	response					155:162	the immune response	144:162	the immune response	144:162	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	8	6	with	interaction	1424:1434	arg1	PD-1					1441:1444	PD-1	1441:1444	PD-1	1441:1444	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	8	7	theme	highest	1355:1361	arg1	variability					1363:1373	the highest variability	1351:1373	the highest variability in occupancy	1351:1386	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	4	8	theme	high	585:588	arg1	proportion					590:599	a high proportion	583:599	a high proportion of polyLacNAc structures at the N219 sequon	583:643	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	4	9	from	PD-L1	499:503	arg1	surface					512:518	the surface	508:518	the surface of breast cancer cell line	508:545	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	1	10	from	regulators	130:139	arg1	immunotherapy					196:208	cancer immunotherapy	189:208	cancer immunotherapy	189:208	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	6	11	theme	protein	1076:1082	arg1	function					1084:1091	the protein function	1072:1091	the protein function	1072:1091	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	12	theme	PD-1	972:975	arg1	PD-L1					946:950	PD-L1	946:950	PD-L1	946:950	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	12	theme	PD-1	972:975	arg1	N116					964:967	N116	964:967	N116	964:967	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	12	theme	PD-1	972:975	arg1	N74					956:958	N74	956:958	N74	956:958	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	5	13	theme	breast	723:728	arg1	MDA-MB-231					730:739	breast MDA-MB-231 or HEK293 cells	723:755	MDA-MB-231	730:739	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	5	14	theme	structures	832:841	arg1	occupancy					783:791	minimum N219 occupancy	770:791	minimum N219 occupancy	770:791	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	5	14	theme	structures	832:841	arg1	contribution					801:812	low contribution	797:812	low contribution of the polyLacNAc structures	797:841	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	3	15	theme	motifs	471:476	arg1	resolution					441:450	the site-specific resolution	423:450	the site-specific resolution of specific glycan motifs	423:476	We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs.
33073996	7	16	with	interaction	1128:1138	arg1	antibodies					1163:1172	clinical antibodies	1154:1172	clinical antibodies	1154:1172	The interaction of PD-L1 with clinical antibodies is also affected by glycosylation.
33073996	6	17	theme	potential	1047:1055	arg1	interaction					1057:1067	this potential interaction	1042:1067	this potential interaction	1042:1067	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	1	18	theme	response	155:162	arg1	inhibitors					88:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	18	theme	response	155:162	arg1	PD-L1/PD-1					110:119	PD-L1/PD-1	110:119	PD-L1/PD-1	110:119	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	18	theme	response	155:162	arg1	targets					178:184	promising targets	168:184	promising targets in cancer immunotherapy	168:208	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	18	theme	response	155:162	arg1	regulators					130:139	key regulators	126:139	key regulators of the immune response	126:162	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	5	19	theme	minimum	770:776	arg1	occupancy					783:791	minimum N219 occupancy	770:791	minimum N219 occupancy	770:791	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	1	20	theme	Immune	70:75	arg1	inhibitors					88:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	20	theme	Immune	70:75	arg1	PD-L1/PD-1					110:119	PD-L1/PD-1	110:119	PD-L1/PD-1	110:119	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	20	theme	Immune	70:75	arg1	regulators					130:139	key regulators	126:139	key regulators of the immune response	126:162	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	6	21	theme	interaction	1057:1067	arg1	impact					1032:1037	the impact	1028:1037	the impact of this potential interaction on the protein function	1028:1091	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	3	22	theme	LC-MS/MS	368:375	arg1	methods					377:383	LC-MS/MS methods	368:383	LC-MS/MS methods	368:383	We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs.
33073996	0	23	from	Impact	28:33	arg1	Binding					38:44	Binding	38:44	Binding to Clinical Antibodies	38:67	PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.
33073996	1	24	theme	checkpoint	77:86	arg1	inhibitors					88:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	24	theme	checkpoint	77:86	arg1	PD-L1/PD-1					110:119	PD-L1/PD-1	110:119	PD-L1/PD-1	110:119	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	24	theme	checkpoint	77:86	arg1	regulators					130:139	key regulators	126:139	key regulators of the immune response	126:162	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	7	25	theme	clinical	1154:1161	arg1	antibodies					1163:1172	clinical antibodies	1154:1172	clinical antibodies	1154:1172	The interaction of PD-L1 with clinical antibodies is also affected by glycosylation.
33073996	1	26	theme	promising	168:176	arg1	targets					178:184	promising targets	168:184	promising targets in cancer immunotherapy	168:208	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	0	27	theme	PD-L1	0:4	arg1	Glycosylation					6:18	PD-L1 Glycosylation	0:18	PD-L1 Glycosylation	0:18	PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.
33073996	6	28	with	interaction	877:887	arg1	N-glycans					894:902	N-glycans	894:902	N-glycans	894:902	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	29	from	impact	1032:1037	arg1	function					1084:1091	the protein function	1072:1091	the protein function	1072:1091	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	8	30	from	variability	1363:1373	arg1	occupancy					1378:1386	occupancy	1378:1386	occupancy	1378:1386	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	4	31	from	sequon	638:643	arg1	proportion					590:599	a high proportion	583:599	a high proportion of polyLacNAc structures at the N219 sequon	583:643	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	7	32	theme	PD-L1	1143:1147	arg1	interaction					1128:1138	The interaction	1124:1138	The interaction of PD-L1 with clinical antibodies	1124:1172	The interaction of PD-L1 with clinical antibodies is also affected by glycosylation.
33073996	4	33	theme	line	542:545	arg1	surface					512:518	the surface	508:518	the surface of breast cancer cell line	508:545	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	5	34	theme	secreted	687:694	arg1	form					696:699	the secreted form	683:699	the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells	683:755	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	2	35	from	sequons	346:352	arg1	distribution					301:312	the distribution	297:312	the distribution of glycoforms at its four NXS/T sequons	297:352	N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons.
33073996	3	36	theme	glycan	464:469	arg1	motifs					471:476	specific glycan motifs	455:476	specific glycan motifs	455:476	We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs.
33073996	4	37	theme	complex	562:568	arg1	glycans					570:576	mostly complex glycans	555:576	mostly complex glycans	555:576	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	8	38	theme	MDA-MB-231	1247:1256	arg1	line					1277:1280	the MDA-MB-231 breast cancer cell line	1243:1280	the MDA-MB-231 breast cancer cell line	1243:1280	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	6	39	theme	interaction	877:887	arg1	modeling					854:861	Molecular modeling	844:861	Molecular modeling of PD-L1/PD-1 interaction with N-glycans	844:902	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	4	40	contain	carries	547:553	arg2	glycans					570:576	mostly complex glycans	555:576	mostly complex glycans	555:576	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	4	40	contain	carries	547:553	arg1	PD-L1					499:503	PD-L1	499:503	PD-L1 on the surface of breast cancer cell line	499:545	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	1	41	theme	cancer	189:194	arg1	immunotherapy					196:208	cancer immunotherapy	189:208	cancer immunotherapy	189:208	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	3	42	theme	energy	401:406	arg1	modulation					408:417	collision energy modulation	391:417	collision energy modulation for the site-specific resolution of specific glycan motifs	391:476	We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs.
33073996	6	43	theme	N74	956:958	arg1	PD-L1					946:950	PD-L1	946:950	PD-L1	946:950	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	43	theme	N74	956:958	arg1	site					938:941	the N219 site	929:941	the N219 site of PD-L1 and N74 and N116 of PD-1	929:975	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	43	theme	N74	956:958	arg1	N74					956:958	N74	956:958	N74	956:958	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	44	theme	PD-L1/PD-1	866:875	arg1	interaction					877:887	PD-L1/PD-1 interaction	866:887	PD-L1/PD-1 interaction with N-glycans	866:902	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	5	45	theme	PD-L1	704:708	arg1	form					696:699	the secreted form	683:699	the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells	683:755	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	8	46	theme	cancer	1265:1270	arg1	line					1277:1280	the MDA-MB-231 breast cancer cell line	1243:1280	the MDA-MB-231 breast cancer cell line	1243:1280	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	3	47	theme	site-specific	427:439	arg1	resolution					441:450	the site-specific resolution	423:450	the site-specific resolution of specific glycan motifs	423:476	We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs.
33073996	2	48	with	interaction	248:258	arg1	PD-1					265:268	PD-1	265:268	PD-1	265:268	N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons.
33073996	5	49	theme	N219	778:781	arg1	occupancy					783:791	minimum N219 occupancy	770:791	minimum N219 occupancy	770:791	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	2	50	theme	PD-L1	230:234	arg1	N-glycosylation					211:225	N-glycosylation	211:225	N-glycosylation of PD-L1	211:234	N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons.
33073996	3	51	theme	specific	455:462	arg1	motifs					471:476	specific glycan motifs	455:476	specific glycan motifs	455:476	We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs.
33073996	2	52	gly	N-glycosylation	211:225	arg1	PD-L1					230:234	PD-L1	230:234	PD-L1	230:234	N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons.
33073996	4	53	theme	breast	523:528	arg1	line					542:545	breast cancer cell line	523:545	breast cancer cell line	523:545	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	5	54	theme	full-length	662:672	arg1	protein					674:680	the full-length protein	658:680	the full-length protein	658:680	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	5	55	theme	HEK293	744:749	arg1	cells					751:755	breast MDA-MB-231 or HEK293 cells	723:755	cells	751:755	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	3	56	theme	collision	391:399	arg1	modulation					408:417	collision energy modulation	391:417	collision energy modulation for the site-specific resolution of specific glycan motifs	391:476	We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs.
33073996	4	57	theme	cell	537:540	arg1	line					542:545	breast cancer cell line	523:545	breast cancer cell line	523:545	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	6	58	from	site	938:941	arg1	glycans					918:924	glycans	918:924	glycans at the N219 site of PD-L1 and N74 and N116 of PD-1	918:975	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	59	theme	Molecular	844:852	arg1	modeling					854:861	Molecular modeling	844:861	Molecular modeling of PD-L1/PD-1 interaction with N-glycans	844:902	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	8	60	theme	cell	1272:1275	arg1	line					1277:1280	the MDA-MB-231 breast cancer cell line	1243:1280	the MDA-MB-231 breast cancer cell line	1243:1280	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	4	61	theme	cancer	530:535	arg1	line					542:545	breast cancer cell line	523:545	breast cancer cell line	523:545	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	6	62	from	point	1109:1113	arg1	unknown					1115:1121	unknown	1115:1121	unknown	1115:1121	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	2	63	theme	glycoforms	317:326	arg1	distribution					301:312	the distribution	297:312	the distribution of glycoforms at its four NXS/T sequons	297:352	N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons.
33073996	8	64	theme	breast	1258:1263	arg1	line					1277:1280	the MDA-MB-231 breast cancer cell line	1243:1280	the MDA-MB-231 breast cancer cell line	1243:1280	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	1	65	theme	key	126:128	arg1	inhibitors					88:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors	70:97	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	65	theme	key	126:128	arg1	PD-L1/PD-1					110:119	PD-L1/PD-1	110:119	PD-L1/PD-1	110:119	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	1	65	theme	key	126:128	arg1	regulators					130:139	key regulators	126:139	key regulators of the immune response	126:162	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	8	66	theme	N219	1323:1326	arg1	likely					1400:1405	likely	1400:1405	likely	1400:1405	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	8	66	theme	N219	1323:1326	arg1	sequon					1328:1333	the N219 sequon	1319:1333	the N219 sequon	1319:1333	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	8	67	theme	polyLacNAc	1290:1299	arg1	glycans					1301:1307	polyLacNAc glycans	1290:1307	polyLacNAc glycans	1290:1307	In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
33073996	4	68	theme	N219	633:636	arg1	sequon					638:643	the N219 sequon	629:643	the N219 sequon	629:643	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	1	69	from	targets	178:184	arg1	immunotherapy					196:208	cancer immunotherapy	189:208	cancer immunotherapy	189:208	Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy.
33073996	4	70	theme	structures	615:624	arg1	proportion					590:599	a high proportion	583:599	a high proportion of polyLacNAc structures at the N219 sequon	583:643	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
33073996	0	71	theme	Clinical	49:56	arg1	Antibodies					58:67	Clinical Antibodies	49:67	Clinical Antibodies	49:67	PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.
33073996	6	72	theme	N219	933:936	arg1	PD-L1					946:950	PD-L1	946:950	PD-L1	946:950	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	72	theme	N219	933:936	arg1	site					938:941	the N219 site	929:941	the N219 site of PD-L1 and N74 and N116 of PD-1	929:975	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	72	theme	N219	933:936	arg1	N74					956:958	N74	956:958	N74	956:958	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	5	73	gly	occupancy	783:791	arg2	structures					832:841	the polyLacNAc structures	817:841	the polyLacNAc structures	817:841	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	5	74	theme	low	797:799	arg1	contribution					801:812	low contribution	797:812	low contribution of the polyLacNAc structures	797:841	Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures.
33073996	6	75	theme	PD-L1	946:950	arg1	PD-L1					946:950	PD-L1	946:950	PD-L1	946:950	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	75	theme	PD-L1	946:950	arg1	site					938:941	the N219 site	929:941	the N219 site of PD-L1 and N74 and N116 of PD-1	929:975	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	6	75	theme	PD-L1	946:950	arg1	N74					956:958	N74	956:958	N74	956:958	Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown.
33073996	4	76	theme	polyLacNAc	604:613	arg1	structures					615:624	polyLacNAc structures	604:624	polyLacNAc structures	604:624	We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon.
34864596	7	0	theme	key	1164:1166	arg1	parts					1168:1172	key parts	1164:1172	key parts	1164:1172	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	7	0	theme	key	1164:1166	arg1	analysis					1144:1151	protein and glycan level analysis	1119:1151	analysis	1144:1151	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	2	1	theme	glycoprotein	368:379	arg1	drugs					381:385	such glycoprotein drugs	363:385	such glycoprotein drugs	363:385	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	10	2	theme	structure	1652:1660	arg1	relationship					1662:1673	no ADCC function - structure relationship	1633:1673	relationship	1662:1673	The results suggested no ADCC function - structure relationship due to the mostly core fucosylated biantennary glycans found.
34864596	1	3	theme	glycoprotein	122:133	arg1	biotherapeutics					141:155	a glycoprotein based biotherapeutics	120:155	a glycoprotein based biotherapeutics	120:155	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	1	3	theme	glycoprotein	122:133	arg1	Omalizumab					108:117	Omalizumab	108:117	Omalizumab	108:117	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	10	4	theme	core	1693:1696	arg1	glycans					1722:1728	the mostly core fucosylated biantennary glycans	1682:1728	the mostly core fucosylated biantennary glycans found	1682:1734	The results suggested no ADCC function - structure relationship due to the mostly core fucosylated biantennary glycans found.
34864596	0	5	theme	N-glycosylation	0:14	arg1	product					99:105	an anti-asthma biotherapeutic product	69:105	an anti-asthma biotherapeutic product	69:105	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	0	5	theme	N-glycosylation	0:14	arg1	structure					16:24	N-glycosylation structure	0:24	N-glycosylation structure	0:24	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	8	6	theme	omalizumab	1297:1306	arg1	characterization					1277:1292	characterization	1277:1292	characterization of omalizumab	1277:1306	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	7	7	theme	glycan	1131:1136	arg1	parts					1168:1172	key parts	1164:1172	key parts	1164:1172	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	7	7	theme	glycan	1131:1136	arg1	analysis					1144:1151	protein and glycan level analysis	1119:1151	analysis	1144:1151	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	3	8	theme	quality	610:616	arg1	CQA					629:631	CQA	629:631	CQA	629:631	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	3	8	theme	quality	610:616	arg1	attribute					618:626	an important critical quality attribute	588:626	an important critical quality attribute (CQA)	588:632	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	3	8	theme	quality	610:616	arg1	glycosylation					558:570	the glycosylation	554:570	the glycosylation of biologics	554:583	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	8	9	from	level	1504:1508	arg1	electrophoresis					1345:1359	capillary SDS gel electrophoresis	1327:1359	capillary SDS gel electrophoresis with UV detection at the protein level	1327:1398	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	8	9	from	level	1504:1508	arg1	electrophoresis					1418:1432	capillary gel electrophoresis	1404:1432	capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level	1404:1508	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	1	10	theme	targeted	193:200	arg1	biopharmaceutical					211:227	the most frequently used targeted antibody biopharmaceutical	168:227	the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use	168:316	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	8	11	theme	important	1231:1239	arg1	relationships					1262:1274	important structure - function relationships	1231:1274	important structure - function relationships	1231:1274	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	5	12	dep	structure	787:795	arg1	the					783:785	the	783:785	the	783:785	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	4	13	theme	linked	661:666	arg1	carbohydrates					668:680	asparagine linked carbohydrates	650:680	asparagine linked carbohydrates	650:680	The profile of asparagine linked carbohydrates is greatly dependent on the manufacturing process.
34864596	5	14	theme	small	740:744	arg1	deviation					746:754	Even a small deviation	733:754	Even a small deviation	733:754	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	3	15	theme	important	591:599	arg1	CQA					629:631	CQA	629:631	CQA	629:631	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	3	15	theme	important	591:599	arg1	attribute					618:626	an important critical quality attribute	588:626	an important critical quality attribute (CQA)	588:632	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	3	15	theme	important	591:599	arg1	glycosylation					558:570	the glycosylation	554:570	the glycosylation of biologics	554:583	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	1	16	theme	biopharmaceutical	211:227	arg1	one					161:163	one	161:163	one	161:163	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	1	16	theme	biopharmaceutical	211:227	arg1	biopharmaceutical					211:227	the most frequently used targeted antibody biopharmaceutical	168:227	the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use	168:316	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	8	17	theme	capillary	1327:1335	arg1	electrophoresis					1345:1359	capillary SDS gel electrophoresis	1327:1359	capillary SDS gel electrophoresis with UV detection at the protein level	1327:1398	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	10	18	theme	biantennary	1710:1720	arg1	glycans					1722:1728	the mostly core fucosylated biantennary glycans	1682:1728	the mostly core fucosylated biantennary glycans found	1682:1734	The results suggested no ADCC function - structure relationship due to the mostly core fucosylated biantennary glycans found.
34864596	5	19	theme	product	846:852	arg1	function					815:822	therefore the function	801:822	therefore the function	801:822	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	5	19	theme	product	846:852	arg1	structure					787:795	structure	787:795	structure	787:795	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	7	20	theme	protein	1047:1053	arg1	therapeutics					1055:1066	protein therapeutics	1047:1066	protein therapeutics	1047:1066	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	8	21	theme	gel	1341:1343	arg1	electrophoresis					1345:1359	capillary SDS gel electrophoresis	1327:1359	capillary SDS gel electrophoresis with UV detection at the protein level	1327:1398	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	7	22	dep	analysis	1144:1151	arg1	both					1174:1177	both	1174:1177	both	1174:1177	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	1	23	theme	based	135:139	arg1	biotherapeutics					141:155	a glycoprotein based biotherapeutics	120:155	a glycoprotein based biotherapeutics	120:155	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	1	23	theme	based	135:139	arg1	Omalizumab					108:117	Omalizumab	108:117	Omalizumab	108:117	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	11	24	theme	drug	1833:1836	arg1	rate					1821:1824	the clearance rate	1807:1824	the clearance rate of the drug	1807:1836	However, the presence of the high mannose structures probably affects the clearance rate of the drug.
34864596	7	25	theme	used	1020:1023	arg1	tools					1025:1029	the frequently used tools	1005:1029	the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control	1005:1218	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	9	26	theme	glycan	1582:1587	arg1	validation					1599:1608	glycan structure validation	1582:1608	glycan structure validation	1582:1608	This latter technique was also used for oligosaccharide sequencing for glycan structure validation.
34864596	4	27	link	linked	661:666	arg1	carbohydrates					668:680	asparagine linked carbohydrates	650:680	asparagine linked carbohydrates	650:680	The profile of asparagine linked carbohydrates is greatly dependent on the manufacturing process.
34864596	1	28	gly	glycoprotein	122:133	arg1	glycoprotein					122:133	a glycoprotein based biotherapeutics	120:155	a glycoprotein based biotherapeutics	120:155	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	0	29	theme	biotherapeutic	84:97	arg1	product					99:105	an anti-asthma biotherapeutic product	69:105	an anti-asthma biotherapeutic product	69:105	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	0	29	theme	biotherapeutic	84:97	arg1	structure					16:24	N-glycosylation structure	0:24	N-glycosylation structure	0:24	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	8	30	with	electrophoresis	1418:1432	arg1	detection					1465:1473	laser induced fluorescent detection	1439:1473	laser induced fluorescent detection	1439:1473	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	8	30	with	electrophoresis	1418:1432	arg1	detection					1369:1377	UV detection	1366:1377	UV detection	1366:1377	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	10	31	gly	fucosylated	1698:1708	arg1	glycans					1722:1728	the mostly core fucosylated biantennary glycans	1682:1728	the mostly core fucosylated biantennary glycans found	1682:1734	The results suggested no ADCC function - structure relationship due to the mostly core fucosylated biantennary glycans found.
34864596	8	32	theme	capillary	1404:1412	arg1	electrophoresis					1418:1432	capillary gel electrophoresis	1404:1432	capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level	1404:1508	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	5	33	contain	have	760:763	arg2	effect					773:778	a major effect	765:778	a major effect	765:778	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	5	33	contain	have	760:763	arg1	deviation					746:754	Even a small deviation	733:754	Even a small deviation	733:754	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	5	34	theme	biotherapeutic	831:844	arg1	product					846:852	the biotherapeutic product	827:852	the biotherapeutic product	827:852	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	1	35	theme	oral	294:297	arg1	use					314:316	oral corticosteroid use	294:316	oral corticosteroid use	294:316	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	7	36	theme	Capillary	964:972	arg1	CE					991:992	CE	991:992	CE	991:992	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	7	36	theme	Capillary	964:972	arg1	electrophoresis					974:988	Capillary electrophoresis	964:988	Capillary electrophoresis (CE)	964:993	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	2	37	theme	required	442:449	arg1	frequency					466:474	the required administration frequency	438:474	the required administration frequency to improve the quality of life in appropriately selected patients	438:540	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	2	38	theme	life	502:505	arg1	quality					491:497	the quality	487:497	the quality of life in appropriately selected patients	487:540	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	2	39	gly	glycoprotein	368:379	arg1	glycoprotein					368:379	such glycoprotein drugs	363:385	such glycoprotein drugs	363:385	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	8	40	with	electrophoresis	1345:1359	arg1	detection					1465:1473	laser induced fluorescent detection	1439:1473	laser induced fluorescent detection	1439:1473	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	8	40	with	electrophoresis	1345:1359	arg1	detection					1369:1377	UV detection	1366:1377	UV detection	1366:1377	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	8	41	theme	fluorescent	1453:1463	arg1	detection					1465:1473	laser induced fluorescent detection	1439:1473	laser induced fluorescent detection	1439:1473	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	7	42	dep	tools	1025:1029	arg1	characterize					1034:1045	characterize	1034:1045	to characterize protein therapeutics	1031:1066	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	7	42	dep	tools	1025:1029	arg1	utilized					1072:1079	utilized	1072:1079	utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control	1072:1218	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	5	43	theme	the	811:813	arg1	function					815:822	therefore the function	801:822	therefore the function	801:822	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	7	44	theme	drug	1183:1186	arg1	development					1188:1198	drug development	1183:1198	drug development	1183:1198	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	6	45	theme	N-glycosylation	886:900	arg1	analysis					902:909	comprehensive N-glycosylation analysis	872:909	comprehensive N-glycosylation analysis	872:909	For this reason, comprehensive N-glycosylation analysis is of high importance during production and release.
34864596	11	46	theme	mannose	1771:1777	arg1	structures					1779:1788	the high mannose structures	1762:1788	the high mannose structures	1762:1788	However, the presence of the high mannose structures probably affects the clearance rate of the drug.
34864596	2	47	theme	such	363:366	arg1	drugs					381:385	such glycoprotein drugs	363:385	such glycoprotein drugs	363:385	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	0	48	theme	omalizumab	57:66	arg1	product					99:105	an anti-asthma biotherapeutic product	69:105	an anti-asthma biotherapeutic product	69:105	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	0	48	theme	omalizumab	57:66	arg1	structure					16:24	N-glycosylation structure	0:24	N-glycosylation structure	0:24	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	8	49	theme	N-linked	1482:1489	arg1	level					1504:1508	the N-linked carbohydrate level	1478:1508	the N-linked carbohydrate level	1478:1508	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	1	50	theme	asthma	239:244	arg1	exacerbations					246:258	asthma exacerbations	239:258	asthma exacerbations	239:258	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	4	51	theme	manufacturing	710:722	arg1	process					724:730	the manufacturing process	706:730	the manufacturing process	706:730	The profile of asparagine linked carbohydrates is greatly dependent on the manufacturing process.
34864596	10	52	theme	ADCC	1636:1639	arg1	function					1641:1648	no ADCC function - structure relationship	1633:1673	function	1641:1648	The results suggested no ADCC function - structure relationship due to the mostly core fucosylated biantennary glycans found.
34864596	2	53	theme	drugs	381:385	arg1	function					332:339	effector function	323:339	effector function	323:339	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	2	53	theme	drugs	381:385	arg1	time					355:358	clearance time	345:358	clearance time	345:358	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	1	54	theme	lung	269:272	arg1	function					274:281	lung function	269:281	lung function	269:281	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	3	55	theme	biologics	575:583	arg1	glycosylation					558:570	the glycosylation	554:570	the glycosylation of biologics	554:583	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	3	55	theme	biologics	575:583	arg1	attribute					618:626	an important critical quality attribute	588:626	an important critical quality attribute (CQA)	588:632	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	7	56	theme	level	1138:1142	arg1	parts					1168:1172	key parts	1164:1172	key parts	1164:1172	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	7	56	theme	level	1138:1142	arg1	analysis					1144:1151	protein and glycan level analysis	1119:1151	analysis	1144:1151	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	9	57	theme	latter	1516:1521	arg1	technique					1523:1531	This latter technique	1511:1531	This latter technique	1511:1531	This latter technique was also used for oligosaccharide sequencing for glycan structure validation.
34864596	6	58	theme	high	917:920	arg1	importance					922:931	high importance	917:931	high importance	917:931	For this reason, comprehensive N-glycosylation analysis is of high importance during production and release.
34864596	3	59	theme	critical	601:608	arg1	CQA					629:631	CQA	629:631	CQA	629:631	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	3	59	theme	critical	601:608	arg1	attribute					618:626	an important critical quality attribute	588:626	an important critical quality attribute (CQA)	588:632	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	3	59	theme	critical	601:608	arg1	glycosylation					558:570	the glycosylation	554:570	the glycosylation of biologics	554:583	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	1	60	theme	used	188:191	arg1	biopharmaceutical					211:227	the most frequently used targeted antibody biopharmaceutical	168:227	the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use	168:316	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	2	61	theme	effector	323:330	arg1	function					332:339	effector function	323:339	effector function	323:339	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	1	62	theme	antibody	202:209	arg1	biopharmaceutical					211:227	the most frequently used targeted antibody biopharmaceutical	168:227	the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use	168:316	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	7	63	theme	biopharmaceutical	1088:1104	arg1	industry					1106:1113	the biopharmaceutical industry	1084:1113	the biopharmaceutical industry	1084:1113	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	8	64	theme	structure	1241:1249	arg1	relationships					1262:1274	important structure - function relationships	1231:1274	important structure - function relationships	1231:1274	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	4	65	theme	carbohydrates	668:680	arg1	dependent					693:701	dependent	693:701	dependent	693:701	The profile of asparagine linked carbohydrates is greatly dependent on the manufacturing process.
34864596	4	65	theme	carbohydrates	668:680	arg1	profile					639:645	The profile	635:645	The profile of asparagine linked carbohydrates	635:680	The profile of asparagine linked carbohydrates is greatly dependent on the manufacturing process.
34864596	10	66	theme	fucosylated	1698:1708	arg1	glycans					1722:1728	the mostly core fucosylated biantennary glycans	1682:1728	the mostly core fucosylated biantennary glycans found	1682:1734	The results suggested no ADCC function - structure relationship due to the mostly core fucosylated biantennary glycans found.
34864596	9	67	theme	oligosaccharide	1551:1565	arg1	sequencing					1567:1576	oligosaccharide sequencing	1551:1576	oligosaccharide sequencing	1551:1576	This latter technique was also used for oligosaccharide sequencing for glycan structure validation.
34864596	8	68	theme	function	1253:1260	arg1	relationships					1262:1274	important structure - function relationships	1231:1274	important structure - function relationships	1231:1274	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	8	69	theme	SDS	1337:1339	arg1	electrophoresis					1345:1359	capillary SDS gel electrophoresis	1327:1359	capillary SDS gel electrophoresis with UV detection at the protein level	1327:1398	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	2	70	dep	function	332:339	arg1	The					319:321	The	319:321	The	319:321	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	0	71	theme	anti-asthma	72:82	arg1	product					99:105	an anti-asthma biotherapeutic product	69:105	an anti-asthma biotherapeutic product	69:105	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	0	71	theme	anti-asthma	72:82	arg1	structure					16:24	N-glycosylation structure	0:24	N-glycosylation structure	0:24	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	7	72	theme	tools	1025:1029	arg1	tools					1025:1029	the frequently used tools	1005:1029	the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control	1005:1218	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	7	72	theme	tools	1025:1029	arg1	one					998:1000	one	998:1000	one	998:1000	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	9	73	theme	structure	1589:1597	arg1	validation					1599:1608	glycan structure validation	1582:1608	glycan structure validation	1582:1608	This latter technique was also used for oligosaccharide sequencing for glycan structure validation.
34864596	2	74	theme	selected	524:531	arg1	patients					533:540	appropriately selected patients	510:540	appropriately selected patients	510:540	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	8	75	theme	UV	1366:1367	arg1	detection					1369:1377	UV detection	1366:1377	UV detection	1366:1377	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	7	76	theme	protein	1119:1125	arg1	parts					1168:1172	key parts	1164:1172	key parts	1164:1172	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	7	76	theme	protein	1119:1125	arg1	analysis					1144:1151	protein and glycan level analysis	1119:1151	analysis	1144:1151	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	3	77	gly	glycosylation	558:570	arg1	biologics					575:583	biologics	575:583	biologics	575:583	Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).
34864596	8	78	link	N-linked	1482:1489	arg1	level					1504:1508	the N-linked carbohydrate level	1478:1508	the N-linked carbohydrate level	1478:1508	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	2	79	from	quality	491:497	arg1	patients					533:540	appropriately selected patients	510:540	appropriately selected patients	510:540	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	8	80	theme	protein	1386:1392	arg1	level					1394:1398	the protein level	1382:1398	the protein level	1382:1398	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	5	81	theme	major	767:771	arg1	effect					773:778	a major effect	765:778	a major effect	765:778	Even a small deviation may have a major effect on the structure and therefore the function of the biotherapeutic product.
34864596	9	82	used	used	1542:1545	arg2	technique					1523:1531	This latter technique	1511:1531	This latter technique	1511:1531	This latter technique was also used for oligosaccharide sequencing for glycan structure validation.
34864596	7	83	theme	quality	1204:1210	arg1	control					1212:1218	quality control	1204:1218	quality control	1204:1218	Capillary electrophoresis (CE) is one of the frequently used tools to characterize protein therapeutics and utilized by the biopharmaceutical industry for protein and glycan level analysis, which are key parts both for drug development and quality control.
34864596	8	84	theme	gel	1414:1416	arg1	electrophoresis					1418:1432	capillary gel electrophoresis	1404:1432	capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level	1404:1508	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	0	85	theme	function	28:35	arg1	characterization					37:52	function characterization	28:52	function characterization	28:52	N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.
34864596	1	86	theme	corticosteroid	299:312	arg1	use					314:316	oral corticosteroid use	294:316	oral corticosteroid use	294:316	Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use.
34864596	2	87	theme	administration	451:464	arg1	frequency					466:474	the required administration frequency	438:474	the required administration frequency to improve the quality of life in appropriately selected patients	438:540	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	11	88	theme	structures	1779:1788	arg1	presence					1750:1757	the presence	1746:1757	the presence of the high mannose structures	1746:1788	However, the presence of the high mannose structures probably affects the clearance rate of the drug.
34864596	11	89	theme	high	1766:1769	arg1	structures					1779:1788	the high mannose structures	1762:1788	the high mannose structures	1762:1788	However, the presence of the high mannose structures probably affects the clearance rate of the drug.
34864596	8	90	theme	induced	1445:1451	arg1	detection					1465:1473	laser induced fluorescent detection	1439:1473	laser induced fluorescent detection	1439:1473	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	6	91	theme	comprehensive	872:884	arg1	analysis					902:909	comprehensive N-glycosylation analysis	872:909	comprehensive N-glycosylation analysis	872:909	For this reason, comprehensive N-glycosylation analysis is of high importance during production and release.
34864596	4	92	dep	linked	661:666	arg1	asparagine					650:659	asparagine	650:659	asparagine	650:659	The profile of asparagine linked carbohydrates is greatly dependent on the manufacturing process.
34864596	11	93	theme	clearance	1811:1819	arg1	rate					1821:1824	the clearance rate	1807:1824	the clearance rate of the drug	1807:1836	However, the presence of the high mannose structures probably affects the clearance rate of the drug.
34864596	2	94	theme	clearance	345:353	arg1	time					355:358	clearance time	345:358	clearance time	345:358	The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients.
34864596	8	95	from	level	1394:1398	arg1	electrophoresis					1345:1359	capillary SDS gel electrophoresis	1327:1359	capillary SDS gel electrophoresis with UV detection at the protein level	1327:1398	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	8	95	from	level	1394:1398	arg1	electrophoresis					1418:1432	capillary gel electrophoresis	1404:1432	capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level	1404:1508	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
34864596	8	96	theme	carbohydrate	1491:1502	arg1	level					1504:1508	the N-linked carbohydrate level	1478:1508	the N-linked carbohydrate level	1478:1508	To reveal important structure - function relationships, characterization of omalizumab is presented using capillary SDS gel electrophoresis with UV detection at the protein level and capillary gel electrophoresis with laser induced fluorescent detection at the N-linked carbohydrate level.
31982929	2	0	theme	surface	495:501	arg1	composition					511:521	cell surface glycome composition	490:521	cell surface glycome composition	490:521	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	5	1	used	used	1051:1054	arg2	We					1043:1044	We	1043:1044	We	1043:1044	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	2	2	theme	innate	364:369	arg1	immunity					371:378	innate immunity	364:378	innate immunity	364:378	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	1	3	theme	molecular	236:244	arg1	interactions					246:257	the molecular interactions	232:257	the molecular interactions that govern the establishment and maintenance of intracellular mutualisms	232:331	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	2	4	theme	cell	490:493	arg1	composition					511:521	cell surface glycome composition	490:521	cell surface glycome composition	490:521	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	2	5	from	understanding	458:470	arg1	establishment					536:548	symbiosis establishment	526:548	symbiosis establishment	526:548	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	8	6	theme	surface	1561:1567	arg1	composition					1576:1586	appropriate cell surface glycan composition	1544:1586	appropriate cell surface glycan composition	1544:1586	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	8	7	theme	Golgi	1486:1490	arg1	processing					1492:1501	functional Golgi processing	1475:1501	functional Golgi processing of N-glycans	1475:1514	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	4	8	theme	first	959:963	arg1	insight					965:971	the first insight	955:971	the first insight into the molecular composition of surface glycans in dinoflagellates	955:1040	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	1	9	dep	establishment	275:287	arg1	the					271:273	the	271:273	the	271:273	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	4	10	theme	cell	900:903	arg1	content					922:928	the cell surface N-glycan content	896:928	the cell surface N-glycan content of B. minutum	896:942	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	6	11	theme	high-mannose	1170:1181	arg1	enrichment					1183:1192	Successful high-mannose enrichment	1159:1192	Successful high-mannose enrichment via kifunensine treatment	1159:1218	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	6	12	theme	sea	1284:1286	arg1	anemone					1288:1294	the model sea anemone Aiptasia (Exaiptasia pallida)	1274:1324	the model sea anemone Aiptasia (Exaiptasia pallida)	1274:1324	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	0	13	theme	Cnidarian-Dinoflagellate	79:102	arg1	Symbiosis					104:112	Cnidarian-Dinoflagellate Symbiosis	79:112	Cnidarian-Dinoflagellate Symbiosis	79:112	N-Linked Surface Glycan Biosynthesis, Composition, Inhibition, and Function in Cnidarian-Dinoflagellate Symbiosis.
31982929	2	14	theme	symbiosis	526:534	arg1	establishment					536:548	symbiosis establishment	526:548	symbiosis establishment	526:548	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	5	15	theme	glycan	1125:1130	arg1	composition					1132:1142	the glycan composition	1121:1142	the glycan composition of B. minutum	1121:1156	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	7	16	theme	glycan	1348:1353	arg1	enrichment					1355:1364	Hybrid glycan enrichment	1341:1364	Hybrid glycan enrichment via swainsonine treatment	1341:1390	Hybrid glycan enrichment via swainsonine treatment, however, could not be confirmed and did not impact colonization.
31982929	6	17	theme	anemone	1288:1294	arg1	colonization					1258:1269	colonization	1258:1269	colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum	1258:1338	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	5	18	dep	inhibitors	1073:1082	arg1	inhibitors					1073:1082	the biosynthesis inhibitors	1056:1082	the biosynthesis inhibitors kifunensine and swainsonine	1056:1110	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	5	18	dep	inhibitors	1073:1082	arg1	swainsonine					1100:1110	swainsonine	1100:1110	swainsonine	1100:1110	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	5	18	dep	inhibitors	1073:1082	arg1	kifunensine					1084:1094	kifunensine	1084:1094	kifunensine	1084:1094	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	0	19	theme	Surface	9:15	arg1	Biosynthesis					24:35	N-Linked Surface Glycan Biosynthesis	0:35	N-Linked Surface Glycan Biosynthesis	0:35	N-Linked Surface Glycan Biosynthesis, Composition, Inhibition, and Function in Cnidarian-Dinoflagellate Symbiosis.
31982929	2	20	from	effects	479:485	arg1	establishment					536:548	symbiosis establishment	526:548	symbiosis establishment	526:548	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	4	21	theme	molecular	982:990	arg1	composition					992:1002	the molecular composition	978:1002	the molecular composition of surface glycans in dinoflagellates	978:1040	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	6	22	theme	model	1278:1282	arg1	anemone					1288:1294	the model sea anemone Aiptasia (Exaiptasia pallida)	1274:1324	the model sea anemone Aiptasia (Exaiptasia pallida)	1274:1324	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	8	23	theme	glycan	1569:1574	arg1	composition					1576:1586	appropriate cell surface glycan composition	1544:1586	appropriate cell surface glycan composition	1544:1586	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	0	24	theme	N-Linked	0:7	arg1	Biosynthesis					24:35	N-Linked Surface Glycan Biosynthesis	0:35	N-Linked Surface Glycan Biosynthesis	0:35	N-Linked Surface Glycan Biosynthesis, Composition, Inhibition, and Function in Cnidarian-Dinoflagellate Symbiosis.
31982929	8	25	theme	colonization	1605:1616	arg1	success					1618:1624	colonization success	1605:1624	colonization success	1605:1624	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	3	26	theme	minutum	693:699	arg1	genome					645:650	the genome	641:650	the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae)	641:724	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	2	27	theme	glycan-lectin	381:393	arg1	interactions					395:406	glycan-lectin interactions	381:406	glycan-lectin interactions	381:406	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	8	28	dep	critical	1519:1526	arg1	ensuring					1596:1603	ensuring	1596:1603	ensuring colonization success by B. minutum	1596:1638	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	8	28	dep	critical	1519:1526	arg1	maintaining					1532:1542	maintaining	1532:1542	maintaining appropriate cell surface glycan composition	1532:1586	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	4	29	theme	minutum	936:942	arg1	content					922:928	the cell surface N-glycan content	896:928	the cell surface N-glycan content of B. minutum	896:942	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	3	30	theme	canonical	598:606	arg1	pathway					630:636	the canonical N-glycan biosynthesis pathway	594:636	the canonical N-glycan biosynthesis pathway	594:636	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	4	31	theme	liquid	827:832	arg1	LC-MS/MS					868:875	LC-MS/MS	868:875	LC-MS/MS	868:875	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	4	31	theme	liquid	827:832	arg1	spectrometry					854:865	coupled liquid chromatography-mass spectrometry	819:865	coupled liquid chromatography-mass spectrometry (LC-MS/MS)	819:876	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	2	32	theme	endosymbioses	435:447	arg1	onset					419:423	the onset	415:423	the onset of marine endosymbioses	415:447	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	0	33	theme	Glycan	17:22	arg1	Biosynthesis					24:35	N-Linked Surface Glycan Biosynthesis	0:35	N-Linked Surface Glycan Biosynthesis	0:35	N-Linked Surface Glycan Biosynthesis, Composition, Inhibition, and Function in Cnidarian-Dinoflagellate Symbiosis.
31982929	5	34	theme	minutum	1150:1156	arg1	composition					1132:1142	the glycan composition	1121:1142	the glycan composition of B. minutum	1121:1156	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	3	35	theme	dinoflagellate	659:672	arg1	minutum					693:699	the dinoflagellate symbiont Breviolum minutum	655:699	the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae)	655:724	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	3	35	theme	dinoflagellate	659:672	arg1	Symbiodiniaceae					709:723	family Symbiodiniaceae	702:723	family Symbiodiniaceae	702:723	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	1	36	dep	hosts	158:162	arg1	corals					171:176	corals	171:176	corals	171:176	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	1	36	dep	hosts	158:162	arg1	anemones					186:193	sea anemones	182:193	sea anemones	182:193	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	2	37	theme	marine	428:433	arg1	endosymbioses					435:447	marine endosymbioses	428:447	marine endosymbioses	428:447	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	4	38	theme	glycans	1015:1021	arg1	composition					992:1002	the molecular composition	978:1002	the molecular composition of surface glycans in dinoflagellates	978:1040	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	3	39	theme	symbiont	674:681	arg1	minutum					693:699	the dinoflagellate symbiont Breviolum minutum	655:699	the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae)	655:724	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	3	39	theme	symbiont	674:681	arg1	Symbiodiniaceae					709:723	family Symbiodiniaceae	702:723	family Symbiodiniaceae	702:723	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	3	40	theme	N-glycan	608:615	arg1	pathway					630:636	the canonical N-glycan biosynthesis pathway	594:636	the canonical N-glycan biosynthesis pathway	594:636	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	1	41	theme	sea	182:184	arg1	anemones					186:193	sea anemones	182:193	sea anemones	182:193	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	6	42	theme	kifunensine	1198:1208	arg1	treatment					1210:1218	kifunensine treatment	1198:1218	kifunensine treatment	1198:1218	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	2	43	theme	effects	479:485	arg1	understanding					458:470	our understanding	454:470	our understanding of the effects of cell surface glycome composition on symbiosis establishment	454:548	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	3	44	theme	GlcNAc-TII	793:802	arg1	exception					764:772	the exception	760:772	the exception of the transferase GlcNAc-TII (MGAT2)	760:810	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	4	45	theme	surface	1007:1013	arg1	glycans					1015:1021	surface glycans	1007:1021	surface glycans	1007:1021	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	7	46	theme	swainsonine	1370:1380	arg1	treatment					1382:1390	swainsonine treatment	1370:1390	swainsonine treatment	1370:1390	Hybrid glycan enrichment via swainsonine treatment, however, could not be confirmed and did not impact colonization.
31982929	3	47	theme	biosynthesis	617:628	arg1	pathway					630:636	the canonical N-glycan biosynthesis pathway	594:636	the canonical N-glycan biosynthesis pathway	594:636	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	1	48	theme	micro-algal	200:210	arg1	symbionts					212:220	micro-algal symbionts	200:220	micro-algal symbionts	200:220	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	1	49	theme	intracellular	308:320	arg1	mutualisms					322:331	intracellular mutualisms	308:331	intracellular mutualisms	308:331	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	4	50	theme	N-glycan	913:920	arg1	content					922:928	the cell surface N-glycan content	896:928	the cell surface N-glycan content of B. minutum	896:942	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	5	51	theme	biosynthesis	1060:1071	arg1	inhibitors					1073:1082	the biosynthesis inhibitors	1056:1082	the biosynthesis inhibitors kifunensine and swainsonine	1056:1110	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	5	51	theme	biosynthesis	1060:1071	arg1	swainsonine					1100:1110	swainsonine	1100:1110	swainsonine	1100:1110	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	5	51	theme	biosynthesis	1060:1071	arg1	kifunensine					1084:1094	kifunensine	1084:1094	kifunensine	1084:1094	We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum.
31982929	6	52	theme	Successful	1159:1168	arg1	enrichment					1183:1192	Successful high-mannose enrichment	1159:1192	Successful high-mannose enrichment via kifunensine treatment	1159:1218	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	8	53	theme	cell	1556:1559	arg1	composition					1576:1586	appropriate cell surface glycan composition	1544:1586	appropriate cell surface glycan composition	1544:1586	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	1	54	theme	mutualisms	322:331	arg1	maintenance					293:303	maintenance	293:303	maintenance	293:303	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	1	54	theme	mutualisms	322:331	arg1	establishment					275:287	establishment	275:287	establishment	275:287	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	4	55	theme	surface	905:911	arg1	content					922:928	the cell surface N-glycan content	896:928	the cell surface N-glycan content of B. minutum	896:942	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	1	56	dep	corals	171:176	arg1	e.g.					165:168	e.g.	165:168	e.g.	165:168	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	2	57	theme	fundamental	339:349	arg1	component					351:359	a fundamental component	337:359	a fundamental component of innate immunity	337:378	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	8	58	theme	functional	1475:1484	arg1	processing					1492:1501	functional Golgi processing	1475:1501	functional Golgi processing of N-glycans	1475:1514	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	3	59	theme	transferase	781:791	arg1	MGAT2					805:809	MGAT2	805:809	MGAT2	805:809	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	3	59	theme	transferase	781:791	arg1	GlcNAc-TII					793:802	the transferase GlcNAc-TII	777:802	the transferase GlcNAc-TII (MGAT2)	777:810	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	3	60	theme	family	702:707	arg1	minutum					693:699	the dinoflagellate symbiont Breviolum minutum	655:699	the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae)	655:724	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	3	60	theme	family	702:707	arg1	Symbiodiniaceae					709:723	family Symbiodiniaceae	702:723	family Symbiodiniaceae	702:723	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	0	61	dep	Biosynthesis	24:35	arg1	Symbiosis					104:112	Cnidarian-Dinoflagellate Symbiosis	79:112	Cnidarian-Dinoflagellate Symbiosis	79:112	N-Linked Surface Glycan Biosynthesis, Composition, Inhibition, and Function in Cnidarian-Dinoflagellate Symbiosis.
31982929	4	62	theme	coupled	819:825	arg1	LC-MS/MS					868:875	LC-MS/MS	868:875	LC-MS/MS	868:875	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	4	62	theme	coupled	819:825	arg1	spectrometry					854:865	coupled liquid chromatography-mass spectrometry	819:865	coupled liquid chromatography-mass spectrometry (LC-MS/MS)	819:876	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	1	63	theme	symbioses	130:138	arg1	success					119:125	The success	115:125	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts	115:220	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	4	64	theme	chromatography-mass	834:852	arg1	LC-MS/MS					868:875	LC-MS/MS	868:875	LC-MS/MS	868:875	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	4	64	theme	chromatography-mass	834:852	arg1	spectrometry					854:865	coupled liquid chromatography-mass spectrometry	819:865	coupled liquid chromatography-mass spectrometry (LC-MS/MS)	819:876	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	6	65	dep	anemone	1288:1294	arg1	Aiptasia					1296:1303	Aiptasia	1296:1303	Aiptasia	1296:1303	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	6	65	dep	anemone	1288:1294	arg1	pallida					1317:1323	pallida	1317:1323	pallida	1317:1323	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	3	66	theme	Breviolum	683:691	arg1	minutum					693:699	the dinoflagellate symbiont Breviolum minutum	655:699	the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae)	655:724	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	3	66	theme	Breviolum	683:691	arg1	Symbiodiniaceae					709:723	family Symbiodiniaceae	702:723	family Symbiodiniaceae	702:723	In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2).
31982929	8	67	theme	N-glycans	1506:1514	arg1	processing					1492:1501	functional Golgi processing	1475:1501	functional Golgi processing of N-glycans	1475:1514	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	4	68	from	composition	992:1002	arg1	dinoflagellates					1026:1040	dinoflagellates	1026:1040	dinoflagellates	1026:1040	Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates.
31982929	2	69	theme	composition	511:521	arg1	effects					479:485	the effects	475:485	the effects of cell surface glycome composition on symbiosis establishment	475:548	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	2	70	from	establishment	536:548	arg1	understanding					458:470	our understanding	454:470	our understanding of the effects of cell surface glycome composition on symbiosis establishment	454:548	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	7	71	theme	Hybrid	1341:1346	arg1	enrichment					1355:1364	Hybrid glycan enrichment	1341:1364	Hybrid glycan enrichment via swainsonine treatment	1341:1390	Hybrid glycan enrichment via swainsonine treatment, however, could not be confirmed and did not impact colonization.
31982929	1	72	theme	cnidarian	148:156	arg1	hosts					158:162	cnidarian hosts	148:162	cnidarian hosts (e.g., corals and sea anemones)	148:194	The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms.
31982929	2	73	theme	glycome	503:509	arg1	composition					511:521	cell surface glycome composition	490:521	cell surface glycome composition	490:521	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	8	74	theme	appropriate	1544:1554	arg1	composition					1576:1586	appropriate cell surface glycan composition	1544:1586	appropriate cell surface glycan composition	1544:1586	We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
31982929	6	75	theme	significant	1234:1244	arg1	decrease					1246:1253	a significant decrease	1232:1253	a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum	1232:1338	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
31982929	2	76	theme	immunity	371:378	arg1	component					351:359	a fundamental component	337:359	a fundamental component of innate immunity	337:378	As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited.
31982929	6	77	from	decrease	1246:1253	arg1	colonization					1258:1269	colonization	1258:1269	colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum	1258:1338	Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum.
33806155	4	0	theme	insect	844:849	arg1	cell					851:854	insect cell	844:854	insect cell	844:854	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	8	1	from	functions	1324:1332	arg1	shielding					1357:1365	immune shielding	1350:1365	immune shielding	1350:1365	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	8	1	from	functions	1324:1332	arg1	effects					1382:1388	negligible effects	1371:1388	negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2	1371:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	8	1	from	functions	1324:1332	arg1	design					1428:1433	subunit vaccine design	1412:1433	subunit vaccine design for SARS-CoV-2	1412:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	1	2	theme	surface	244:250	arg1	proteins					252:259	viral surface proteins	238:259	viral surface proteins with tolerogenic host-like structures	238:297	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	4	3	theme	derived	856:862	arg1	domain					881:886	insect cell derived receptor binding domain	844:886	insect cell derived receptor binding domain (RBD)	844:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	3	theme	derived	856:862	arg1	RBD					889:891	RBD	889:891	RBD	889:891	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	3	4	theme	large	513:517	arg1	family					519:524	a large family	511:524	a large family of initiating enzymes with variable expression in cells and tissues	511:592	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	8	5	gly	O-glycosylation	1393:1407	arg1	vaccine					1420:1426	subunit vaccine design	1412:1433	subunit vaccine design for SARS-CoV-2	1412:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	8	5	gly	O-glycosylation	1393:1407	arg1	subunit					1412:1418	subunit vaccine design	1412:1433	subunit vaccine design for SARS-CoV-2	1412:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	4	6	theme	cell-produced	814:826	arg1	ectodomains					828:838	protein S-insect cell or human cell-produced ectodomains	783:838	ectodomains	828:838	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	5	7	from	patterns	950:957	arg1	pattern					1023:1029	a distinct pattern	1012:1029	a distinct pattern of the monomeric RBD	1012:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	7	from	patterns	950:957	arg1	origin					1000:1005	different cell origin	985:1005	different cell origin	985:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	7	from	patterns	950:957	arg1	RBD					1048:1050	the monomeric RBD	1034:1050	the monomeric RBD	1034:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	7	from	patterns	950:957	arg1	ectodomains					970:980	the two ectodomains	962:980	the two ectodomains of different cell origin	962:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	2	8	theme	protein	319:325	arg1	S					327:327	SARS-CoV-2 surface protein S	300:327	SARS-CoV-2 surface protein S	300:327	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	1	9	theme	glycosylation	182:194	arg1	machinery					196:204	its glycosylation machinery	178:204	its glycosylation machinery	178:204	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	6	10	gly	O-glycosites	1078:1089	arg2	O-glycosites					1078:1089	16 out of 25 O-glycosites	1065:1089	16 out of 25 O-glycosites	1065:1089	Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites.
33806155	5	11	theme	distinct	1014:1021	arg1	pattern					1023:1029	a distinct pattern	1012:1029	a distinct pattern of the monomeric RBD	1012:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	2	12	theme	SARS-CoV-2	300:309	arg1	S					327:327	SARS-CoV-2 surface protein S	300:327	SARS-CoV-2 surface protein S	300:327	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	8	13	from	effects	1382:1388	arg1	design					1428:1433	subunit vaccine design	1412:1433	subunit vaccine design for SARS-CoV-2	1412:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	4	14	theme	binding	873:879	arg1	domain					881:886	insect cell derived receptor binding domain	844:886	insect cell derived receptor binding domain (RBD)	844:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	14	theme	binding	873:879	arg1	RBD					889:891	RBD	889:891	RBD	889:891	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	8	15	theme	vaccine	1420:1426	arg1	design					1428:1433	subunit vaccine design	1412:1433	subunit vaccine design for SARS-CoV-2	1412:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	8	16	theme	complementary	1310:1322	arg1	functions					1324:1332	possible complementary functions	1301:1332	possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2	1301:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	5	17	theme	origin	1000:1005	arg1	pattern					1023:1029	a distinct pattern	1012:1029	a distinct pattern of the monomeric RBD	1012:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	17	theme	origin	1000:1005	arg1	origin					1000:1005	different cell origin	985:1005	different cell origin	985:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	17	theme	origin	1000:1005	arg1	RBD					1048:1050	the monomeric RBD	1034:1050	the monomeric RBD	1034:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	17	theme	origin	1000:1005	arg1	ectodomains					970:980	the two ectodomains	962:980	the two ectodomains of different cell origin	962:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	3	18	theme	variable	553:560	arg1	expression					562:571	variable expression	553:571	variable expression in cells and tissues	553:592	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	6	19	theme	known	1134:1138	arg1	N-glycosites					1140:1151	known N-glycosites	1134:1151	known N-glycosites	1134:1151	Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites.
33806155	4	20	gly	glycosylation	732:744	arg2	sites					746:750	O-linked glycosylation sites	723:750	O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	723:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	1	21	theme	translation	146:156	arg1	processes					158:166	the host translation processes	137:166	the host translation processes	137:166	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	4	22	theme	well-established	647:662	arg1	workflows					681:689	our well-established O-glycoproteomic workflows	643:689	our well-established O-glycoproteomic workflows	643:689	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	7	23	located	found	1193:1197	arg2	O-glycosylation					1163:1177	O-glycosylation	1163:1177	O-glycosylation	1163:1177	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	7	23	located	found	1193:1197	arg1	peptides					1202:1209	peptides	1202:1209	peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy	1202:1284	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	2	24	link	N-linked	407:414	arg1	glycans					416:422	N-linked glycans	407:422	N-linked glycans	407:422	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	4	25	theme	glycosylation	732:744	arg1	sites					746:750	O-linked glycosylation sites	723:750	O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	723:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	6	26	from	N-glycosites	1140:1151	arg1	acids					1123:1127	three amino acids	1111:1127	three amino acids from known N-glycosites	1111:1151	Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites.
33806155	5	27	theme	monomeric	1038:1046	arg1	RBD					1048:1050	the monomeric RBD	1034:1050	the monomeric RBD	1034:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	1	28	dep	hijack	121:126	arg1	cover					232:236	cover	232:236	cover viral surface proteins with tolerogenic host-like structures	232:297	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	4	29	dep	derived	856:862	arg1	cell					851:854	insect cell	844:854	insect cell	844:854	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	5	30	theme	similar	942:948	arg1	patterns					950:957	similar patterns	942:957	similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD	942:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	8	31	from	design	1428:1433	arg1	functions					1324:1332	possible complementary functions	1301:1332	possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2	1301:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	4	32	theme	precise	702:708	arg1	positions					710:718	the precise positions	698:718	the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	698:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	0	33	theme	Site-Specific	0:12	arg1	O-Glycosylation					14:28	Site-Specific O-Glycosylation	0:28	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein	0:65	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells.
33806155	1	34	theme	tolerogenic	266:276	arg1	structures					288:297	tolerogenic host-like structures	266:297	tolerogenic host-like structures	266:297	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	7	35	theme	low	1264:1266	arg1	occupancy					1276:1284	low overall occupancy	1264:1284	low overall occupancy	1264:1284	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	2	36	theme	glycans	416:422	arg1	shield					397:402	shield	397:402	shield	397:402	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	8	37	theme	O-glycans	1337:1345	arg1	functions					1324:1332	possible complementary functions	1301:1332	possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2	1301:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	8	38	theme	immune	1350:1355	arg1	shielding					1357:1365	immune shielding	1350:1365	immune shielding	1350:1365	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	3	39	with	enzymes	540:546	arg1	expression					562:571	variable expression	553:571	variable expression in cells and tissues	553:592	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	4	40	theme	S-insect	791:798	arg1	cell					800:803	protein S-insect cell or human cell-produced ectodomains	783:838	cell	800:803	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	0	41	theme	SARS-CoV-2	42:51	arg1	Protein					59:65	SARS-CoV-2 Spike Protein	42:65	SARS-CoV-2 Spike Protein	42:65	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells.
33806155	1	42	with	proteins	252:259	arg1	structures					288:297	tolerogenic host-like structures	266:297	tolerogenic host-like structures	266:297	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	2	43	theme	few	431:433	arg1	O-glycosites					435:446	a few O-glycosites	429:446	a few O-glycosites	429:446	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	0	44	theme	Protein	59:65	arg1	Analysis					30:37	Site-Specific O-Glycosylation Analysis	0:37	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein	0:65	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells.
33806155	5	45	theme	cell	995:998	arg1	origin					1000:1005	different cell origin	985:1005	different cell origin	985:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	4	46	theme	different	761:769	arg1	entities					771:778	three different entities	755:778	three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	755:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	47	link	O-linked	723:730	arg1	sites					746:750	O-linked glycosylation sites	723:750	O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	723:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	6	48	located	located	1096:1102	arg2	O-glycosites					1078:1089	16 out of 25 O-glycosites	1065:1089	16 out of 25 O-glycosites	1065:1089	Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites.
33806155	6	48	located	located	1096:1102	arg1	acids					1123:1127	three amino acids	1111:1127	three amino acids from known N-glycosites	1111:1151	Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites.
33806155	6	49	gly	N-glycosites	1140:1151	arg2	N-glycosites					1140:1151	known N-glycosites	1134:1151	known N-glycosites	1134:1151	Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites.
33806155	8	50	theme	O-glycosylation	1393:1407	arg1	shielding					1357:1365	immune shielding	1350:1365	immune shielding	1350:1365	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	8	50	theme	O-glycosylation	1393:1407	arg1	effects					1382:1388	negligible effects	1371:1388	negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2	1371:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	3	51	theme	O-glycans	484:492	arg1	difficult					607:615	difficult	607:615	difficult	607:615	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	3	51	theme	O-glycans	484:492	arg1	location					472:479	The location	468:479	The location of O-glycans	468:492	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	1	52	theme	viral	238:242	arg1	proteins					252:259	viral surface proteins	238:259	viral surface proteins with tolerogenic host-like structures	238:297	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	2	53	from	trimer	343:348	arg1	surface					363:369	the viral surface	353:369	the viral surface	353:369	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	6	54	theme	amino	1117:1121	arg1	acids					1123:1127	three amino acids	1111:1127	three amino acids from known N-glycosites	1111:1151	Strikingly, 16 out of 25 O-glycosites were located within three amino acids from known N-glycosites.
33806155	8	55	from	shielding	1357:1365	arg1	design					1428:1433	subunit vaccine design	1412:1433	subunit vaccine design for SARS-CoV-2	1412:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	4	56	theme	human	808:812	arg1	ectodomains					828:838	protein S-insect cell or human cell-produced ectodomains	783:838	ectodomains	828:838	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	57	link	derived	856:862	arg1	domain					881:886	insect cell derived receptor binding domain	844:886	insect cell derived receptor binding domain (RBD)	844:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	57	link	derived	856:862	arg1	RBD					889:891	RBD	889:891	RBD	889:891	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	3	58	theme	initiating	529:538	arg1	enzymes					540:546	initiating enzymes	529:546	initiating enzymes with variable expression in cells and tissues	529:592	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	4	59	theme	ectodomains	828:838	arg1	entities					771:778	three different entities	755:778	three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	755:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	2	60	theme	surface	311:317	arg1	S					327:327	SARS-CoV-2 surface protein S	300:327	SARS-CoV-2 surface protein S	300:327	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	3	61	theme	enzymes	540:546	arg1	family					519:524	a large family	511:524	a large family of initiating enzymes with variable expression in cells and tissues	511:592	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	8	62	theme	subunit	1412:1418	arg1	design					1428:1433	subunit vaccine design	1412:1433	subunit vaccine design for SARS-CoV-2	1412:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	4	63	theme	receptor	864:871	arg1	domain					881:886	insect cell derived receptor binding domain	844:886	insect cell derived receptor binding domain (RBD)	844:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	63	theme	receptor	864:871	arg1	RBD					889:891	RBD	889:891	RBD	889:891	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	64	theme	O-glycoproteomic	664:679	arg1	workflows					681:689	our well-established O-glycoproteomic workflows	643:689	our well-established O-glycoproteomic workflows	643:689	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	7	65	contain	had	1260:1262	arg2	occupancy					1276:1284	low overall occupancy	1264:1284	low overall occupancy	1264:1284	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	7	65	contain	had	1260:1262	arg1	peptides					1202:1209	peptides	1202:1209	peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy	1202:1284	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	4	66	theme	domain	881:886	arg1	entities					771:778	three different entities	755:778	three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	755:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	0	67	theme	Insect	79:84	arg1	Cells					96:100	Insect and Human Cells	79:100	Insect and Human Cells	79:100	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells.
33806155	4	68	from	entities	771:778	arg1	positions					710:718	the precise positions	698:718	the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	698:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	1	69	theme	host	141:144	arg1	processes					158:166	the host translation processes	137:166	the host translation processes	137:166	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	0	70	theme	Human	90:94	arg1	Cells					96:100	Insect and Human Cells	79:100	Insect and Human Cells	79:100	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells.
33806155	4	71	from	sites	746:750	arg1	entities					771:778	three different entities	755:778	three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	755:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	4	72	theme	O-linked	723:730	arg1	sites					746:750	O-linked glycosylation sites	723:750	O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	723:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	5	73	theme	RBD	1048:1050	arg1	pattern					1023:1029	a distinct pattern	1012:1029	a distinct pattern of the monomeric RBD	1012:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	73	theme	RBD	1048:1050	arg1	origin					1000:1005	different cell origin	985:1005	different cell origin	985:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	73	theme	RBD	1048:1050	arg1	RBD					1048:1050	the monomeric RBD	1034:1050	the monomeric RBD	1034:1050	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	5	73	theme	RBD	1048:1050	arg1	ectodomains					970:980	the two ectodomains	962:980	the two ectodomains of different cell origin	962:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	7	74	theme	overall	1268:1274	arg1	occupancy					1276:1284	low overall occupancy	1264:1284	low overall occupancy	1264:1284	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	5	75	gly	O-glycosites	907:918	arg2	O-glycosites					907:918	25 O-glycosites	904:918	25 O-glycosites	904:918	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	4	76	theme	sites	746:750	arg1	positions					710:718	the precise positions	698:718	the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	698:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	0	77	theme	O-Glycosylation	14:28	arg1	Analysis					30:37	Site-Specific O-Glycosylation Analysis	0:37	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein	0:65	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells.
33806155	4	78	from	positions	710:718	arg1	entities					771:778	three different entities	755:778	three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	755:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	7	79	gly	O-glycosylation	1163:1177	arg1	peptides					1202:1209	peptides	1202:1209	peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy	1202:1284	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	7	79	gly	O-glycosylation	1163:1177	arg2	peptides					1202:1209	peptides	1202:1209	peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy	1202:1284	However, O-glycosylation was primarily found on peptides that were unoccupied by N-glycans, and otherwise had low overall occupancy.
33806155	1	80	theme	host-like	278:286	arg1	structures					288:297	tolerogenic host-like structures	266:297	tolerogenic host-like structures	266:297	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	4	81	used	used	638:641	arg2	we					635:636	we	635:636	we	635:636	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	1	82	theme	Enveloped	103:111	arg1	viruses					113:119	Enveloped viruses	103:119	Enveloped viruses	103:119	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	2	83	theme	N-linked	407:414	arg1	glycans					416:422	N-linked glycans	407:422	N-linked glycans	407:422	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	8	84	theme	possible	1301:1308	arg1	functions					1324:1332	possible complementary functions	1301:1332	possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2	1301:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	3	85	from	expression	562:571	arg1	tissues					586:592	tissues	586:592	tissues	586:592	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	3	85	from	expression	562:571	arg1	cells					576:580	cells	576:580	cells	576:580	The location of O-glycans is controlled by a large family of initiating enzymes with variable expression in cells and tissues and hence is difficult to predict.
33806155	0	86	theme	Spike	53:57	arg1	Protein					59:65	SARS-CoV-2 Spike Protein	42:65	SARS-CoV-2 Spike Protein	42:65	Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells.
33806155	2	87	gly	O-glycosites	435:446	arg2	O-glycosites					435:446	a few O-glycosites	429:446	a few O-glycosites	429:446	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
33806155	4	88	theme	protein	783:789	arg1	cell					800:803	protein S-insect cell or human cell-produced ectodomains	783:838	cell	800:803	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	5	89	theme	different	985:993	arg1	origin					1000:1005	different cell origin	985:1005	different cell origin	985:1005	In total 25 O-glycosites were identified, with similar patterns in the two ectodomains of different cell origin, and a distinct pattern of the monomeric RBD.
33806155	4	90	theme	cell	800:803	arg1	entities					771:778	three different entities	755:778	three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD)	755:892	Here, we used our well-established O-glycoproteomic workflows to map the precise positions of O-linked glycosylation sites on three different entities of protein S-insect cell or human cell-produced ectodomains, or insect cell derived receptor binding domain (RBD).
33806155	8	91	theme	negligible	1371:1380	arg1	effects					1382:1388	negligible effects	1371:1388	negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2	1371:1448	This suggests possible complementary functions of O-glycans in immune shielding and negligible effects of O-glycosylation on subunit vaccine design for SARS-CoV-2.
33806155	1	92	theme	variable	216:223	arg1	extent					225:230	a variable extent	214:230	a variable extent	214:230	Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures.
33806155	2	93	theme	viral	357:361	arg1	surface					363:369	the viral surface	353:369	the viral surface	353:369	SARS-CoV-2 surface protein S presents as a trimer on the viral surface and is covered by a dense shield of N-linked glycans, and a few O-glycosites have been reported.
29465311	7	0	theme	GCS1	1196:1199	arg1	expression					1201:1210	increased GCS1 expression	1186:1210	increased GCS1 expression	1186:1210	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	7	1	theme	lipid	1278:1282	arg1	accumulation					1284:1295	reduced lipid accumulation	1270:1295	reduced lipid accumulation	1270:1295	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	1	2	theme	fatty	239:243	arg1	disease					251:257	nonalcoholic fatty liver disease	226:257	nonalcoholic fatty liver disease	226:257	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	8	3	theme	function	1338:1345	arg1	p32					1304:1306	p32	1304:1306	p32	1304:1306	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	3	theme	function	1338:1345	arg1	regulators					1321:1330	regulators	1321:1330	regulators of ER function and lipid homeostasis	1321:1367	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	3	theme	function	1338:1345	arg1	targets					1399:1405	potential therapeutic targets	1377:1405	potential therapeutic targets for the treatment of obesity and diabetes.-Liu	1377:1452	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	3	theme	function	1338:1345	arg1	GCS1					1312:1315	GCS1	1312:1315	GCS1	1312:1315	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	6	4	theme	GCS1	943:946	arg1	expression					948:957	increased GCS1 expression	933:957	increased GCS1 expression	933:957	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	8	5	theme	L.	1470:1471	arg1	p32					1521:1523	Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32	1455:1523	Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32	1455:1523	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	1	6	theme	liver	245:249	arg1	disease					251:257	nonalcoholic fatty liver disease	226:257	nonalcoholic fatty liver disease	226:257	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	7	7	theme	ER	1246:1247	arg1	stress					1249:1254	fatty acid-induced ER stress	1227:1254	fatty acid-induced ER stress	1227:1254	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	6	8	theme	increased	933:941	arg1	expression					948:957	increased GCS1 expression	933:957	increased GCS1 expression	933:957	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	8	9	theme	diabetes.-Liu	1440:1452	arg1	treatment					1415:1423	the treatment	1411:1423	the treatment of obesity and diabetes.-Liu	1411:1452	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	6	10	theme	ER	1031:1032	arg1	activation					1067:1076	ER stress-associated lipogenic gene activation	1031:1076	ER stress-associated lipogenic gene activation	1031:1076	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	4	11	theme	ER	638:639	arg1	stress					641:646	fatty acid-induced ER stress	619:646	fatty acid-induced ER stress	619:646	Here, we show that p32 promotes lipid biosynthesis by modulating fatty acid-induced ER stress.
29465311	8	12	theme	homeostasis	1357:1367	arg1	p32					1304:1306	p32	1304:1306	p32	1304:1306	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	12	theme	homeostasis	1357:1367	arg1	regulators					1321:1330	regulators	1321:1330	regulators of ER function and lipid homeostasis	1321:1367	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	12	theme	homeostasis	1357:1367	arg1	targets					1399:1405	potential therapeutic targets	1377:1405	potential therapeutic targets for the treatment of obesity and diabetes.-Liu	1377:1452	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	12	theme	homeostasis	1357:1367	arg1	GCS1					1312:1315	GCS1	1312:1315	GCS1	1312:1315	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	4	13	theme	lipid	586:590	arg1	biosynthesis					592:603	lipid biosynthesis	586:603	lipid biosynthesis	586:603	Here, we show that p32 promotes lipid biosynthesis by modulating fatty acid-induced ER stress.
29465311	7	14	theme	fatty	1227:1231	arg1	stress					1249:1254	fatty acid-induced ER stress	1227:1254	fatty acid-induced ER stress	1227:1254	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	2	15	theme	oxidation	407:415	arg1	regulation					355:364	the regulation	351:364	the regulation of oxidative phosphorylation and glucose oxidation	351:415	p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation.
29465311	8	16	theme	therapeutic	1387:1397	arg1	targets					1399:1405	potential therapeutic targets	1377:1405	potential therapeutic targets for the treatment of obesity and diabetes.-Liu	1377:1452	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	5	17	theme	lysosome-dependent	886:903	arg1	manner					905:910	a lysosome-dependent manner	884:910	a lysosome-dependent manner	884:910	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	2	18	theme	phosphorylation	379:393	arg1	regulation					355:364	the regulation	351:364	the regulation of oxidative phosphorylation and glucose oxidation	351:415	p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation.
29465311	7	19	theme	acid-induced	1233:1244	arg1	stress					1249:1254	fatty acid-induced ER stress	1227:1254	fatty acid-induced ER stress	1227:1254	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	6	20	theme	lipogenic	1052:1060	arg1	activation					1067:1076	ER stress-associated lipogenic gene activation	1031:1076	ER stress-associated lipogenic gene activation	1031:1076	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	8	21	theme	potential	1377:1385	arg1	targets					1399:1405	potential therapeutic targets	1377:1405	potential therapeutic targets for the treatment of obesity and diabetes.-Liu	1377:1452	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	2	22	theme	oxidative	369:377	arg1	phosphorylation					379:393	oxidative phosphorylation	369:393	oxidative phosphorylation	369:393	p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation.
29465311	5	23	theme	ER	770:771	arg1	glucosidase					745:755	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I	682:757	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1)	682:764	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	23	theme	ER	770:771	arg1	glucosidase					788:798	an ER lumen-anchored glucosidase	767:798	an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins	767:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	23	theme	ER	770:771	arg1	essential					808:816	essential	808:816	essential	808:816	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	1	24	theme	Sustained	82:90	arg1	stress					119:124	Sustained endoplasmic reticulum (ER) stress	82:124	Sustained endoplasmic reticulum (ER) stress	82:124	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	3	25	theme	p32	418:420	arg1	ablation					422:429	p32 ablation	418:429	p32 ablation	418:429	p32 ablation is associated with resistance to age-associated and diet-induced obesity through a mechanism that remains largely unknown.
29465311	1	26	theme	insulin	260:266	arg1	resistance					268:277	insulin resistance	260:277	insulin resistance	260:277	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	27	theme	endoplasmic	92:102	arg1	ER					115:116	ER	115:116	ER	115:116	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	27	theme	endoplasmic	92:102	arg1	reticulum					104:112	endoplasmic reticulum	92:112	Sustained endoplasmic reticulum (ER) stress	82:124	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	28	theme	many	167:170	arg1	diabetes					293:300	diabetes	293:300	diabetes	293:300	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	28	theme	many	167:170	arg1	disease					217:223	cardiovascular disease	202:223	cardiovascular disease	202:223	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	28	theme	many	167:170	arg1	resistance					268:277	insulin resistance	260:277	insulin resistance	260:277	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	28	theme	many	167:170	arg1	diseases					182:189	many metabolic diseases	167:189	many metabolic diseases	167:189	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	28	theme	many	167:170	arg1	obesity					280:286	obesity	280:286	obesity	280:286	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	28	theme	many	167:170	arg1	disease					251:257	nonalcoholic fatty liver disease	226:257	nonalcoholic fatty liver disease	226:257	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	5	29	theme	N-linked	840:847	arg1	glycoproteins					849:861	N-linked glycoproteins	840:861	N-linked glycoproteins	840:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	30	theme	mannosyl-oligosaccharide	720:743	arg1	glucosidase					745:755	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I	682:757	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1)	682:764	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	30	theme	mannosyl-oligosaccharide	720:743	arg1	GCS1					760:763	GCS1	760:763	GCS1	760:763	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	30	theme	mannosyl-oligosaccharide	720:743	arg1	glucosidase					788:798	an ER lumen-anchored glucosidase	767:798	an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins	767:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	30	theme	mannosyl-oligosaccharide	720:743	arg1	essential					808:816	essential	808:816	essential	808:816	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	1	31	theme	reticulum	104:112	arg1	stress					119:124	Sustained endoplasmic reticulum (ER) stress	82:124	Sustained endoplasmic reticulum (ER) stress	82:124	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	8	32	theme	obesity	1428:1434	arg1	treatment					1415:1423	the treatment	1411:1423	the treatment of obesity and diabetes.-Liu	1411:1452	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	1	33	theme	metabolic	172:180	arg1	diabetes					293:300	diabetes	293:300	diabetes	293:300	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	33	theme	metabolic	172:180	arg1	disease					217:223	cardiovascular disease	202:223	cardiovascular disease	202:223	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	33	theme	metabolic	172:180	arg1	resistance					268:277	insulin resistance	260:277	insulin resistance	260:277	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	33	theme	metabolic	172:180	arg1	diseases					182:189	many metabolic diseases	167:189	many metabolic diseases	167:189	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	33	theme	metabolic	172:180	arg1	obesity					280:286	obesity	280:286	obesity	280:286	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	33	theme	metabolic	172:180	arg1	disease					251:257	nonalcoholic fatty liver disease	226:257	nonalcoholic fatty liver disease	226:257	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	0	34	theme	ER	14:15	arg1	stress					17:22	ER stress	14:22	ER stress	14:22	p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	35	theme	lipid	1351:1355	arg1	homeostasis					1357:1367	lipid homeostasis	1351:1367	lipid homeostasis	1351:1367	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	7	36	theme	increased	1186:1194	arg1	expression					1201:1210	increased GCS1 expression	1186:1210	increased GCS1 expression	1186:1210	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	1	37	theme	diseases	182:189	arg1	development					152:162	the development	148:162	the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes	148:300	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	0	38	theme	lipid	28:32	arg1	homeostasis					34:44	lipid homeostasis	28:44	lipid homeostasis	28:44	p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	39	theme	ER	1535:1536	arg1	stress					1538:1543	ER stress	1535:1543	ER stress	1535:1543	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	8	40	theme	GCS1	1586:1589	arg1	expression					1591:1600	GCS1 expression	1586:1600	GCS1 expression	1586:1600	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	2	41	theme	glucose	399:405	arg1	oxidation					407:415	glucose oxidation	399:415	glucose oxidation	399:415	p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation.
29465311	6	42	theme	Fasn	1129:1132	arg1	down-regulation					1102:1116	the down-regulation	1098:1116	the down-regulation of Srebp1, Fasn, and Acc	1098:1141	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	6	43	theme	stress-associated	1034:1050	arg1	activation					1067:1076	ER stress-associated lipogenic gene activation	1031:1076	ER stress-associated lipogenic gene activation	1031:1076	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	6	44	theme	gene	1062:1065	arg1	activation					1067:1076	ER stress-associated lipogenic gene activation	1031:1076	ER stress-associated lipogenic gene activation	1031:1076	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	6	45	theme	Srebp1	1121:1126	arg1	down-regulation					1102:1116	the down-regulation	1098:1116	the down-regulation of Srebp1, Fasn, and Acc	1098:1141	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	7	46	theme	p32	1173:1175	arg1	suppression					1158:1168	suppression	1158:1168	suppression of p32	1158:1175	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	6	47	theme	ER	989:990	arg1	stress					992:997	fatty acid-induced ER stress	970:997	fatty acid-induced ER stress	970:997	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	7	48	theme	reduced	1270:1276	arg1	accumulation					1284:1295	reduced lipid accumulation	1270:1295	reduced lipid accumulation	1270:1295	Consistently, suppression of p32 leads to increased GCS1 expression and alleviates fatty acid-induced ER stress, resulting in reduced lipid accumulation.
29465311	5	49	gly	glycoproteins	849:861	arg1	glycoproteins					849:861	N-linked glycoproteins	840:861	N-linked glycoproteins	840:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	2	50	theme	multicompartmental	312:329	arg1	p32					303:305	p32	303:305	p32	303:305	p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation.
29465311	2	50	theme	multicompartmental	312:329	arg1	protein					331:337	a multicompartmental protein	310:337	a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation	310:415	p32 is a multicompartmental protein involved in the regulation of oxidative phosphorylation and glucose oxidation.
29465311	6	51	theme	acid-induced	976:987	arg1	stress					992:997	fatty acid-induced ER stress	970:997	fatty acid-induced ER stress	970:997	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	5	52	theme	endoplasmic	682:692	arg1	glucosidase					745:755	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I	682:757	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1)	682:764	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	52	theme	endoplasmic	682:692	arg1	GCS1					760:763	GCS1	760:763	GCS1	760:763	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	52	theme	endoplasmic	682:692	arg1	glucosidase					788:798	an ER lumen-anchored glucosidase	767:798	an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins	767:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	52	theme	endoplasmic	682:692	arg1	essential					808:816	essential	808:816	essential	808:816	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	8	53	theme	lipid	1549:1553	arg1	homeostasis					1555:1565	lipid homeostasis	1549:1565	lipid homeostasis	1549:1565	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	6	54	theme	fatty	970:974	arg1	stress					992:997	fatty acid-induced ER stress	970:997	fatty acid-induced ER stress	970:997	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	5	55	theme	reticulum-anchored	694:711	arg1	glucosidase					745:755	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I	682:757	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1)	682:764	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	55	theme	reticulum-anchored	694:711	arg1	GCS1					760:763	GCS1	760:763	GCS1	760:763	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	55	theme	reticulum-anchored	694:711	arg1	glucosidase					788:798	an ER lumen-anchored glucosidase	767:798	an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins	767:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	55	theme	reticulum-anchored	694:711	arg1	essential					808:816	essential	808:816	essential	808:816	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	56	link	N-linked	840:847	arg1	glycoproteins					849:861	N-linked glycoproteins	840:861	N-linked glycoproteins	840:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	8	57	theme	ER	1335:1336	arg1	function					1338:1345	ER function	1335:1345	ER function	1335:1345	Thus, p32 and GCS1 are regulators of ER function and lipid homeostasis and are potential therapeutic targets for the treatment of obesity and diabetes.-Liu, Y., Leslie, P. L., Jin, A., Itahana, K., Graves, L. M., Zhang, Y. p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	1	58	theme	cardiovascular	202:215	arg1	disease					217:223	cardiovascular disease	202:223	cardiovascular disease	202:223	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	5	59	theme	enzyme	713:718	arg1	glucosidase					745:755	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I	682:757	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1)	682:764	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	59	theme	enzyme	713:718	arg1	GCS1					760:763	GCS1	760:763	GCS1	760:763	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	59	theme	enzyme	713:718	arg1	glucosidase					788:798	an ER lumen-anchored glucosidase	767:798	an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins	767:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	59	theme	enzyme	713:718	arg1	essential					808:816	essential	808:816	essential	808:816	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	60	theme	glycoproteins	849:861	arg1	processing					826:835	the processing	822:835	the processing of N-linked glycoproteins	822:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	3	61	theme	diet-induced	483:494	arg1	obesity					496:502	diet-induced obesity	483:502	diet-induced obesity	483:502	p32 ablation is associated with resistance to age-associated and diet-induced obesity through a mechanism that remains largely unknown.
29465311	0	62	theme	GCS1	65:68	arg1	expression					70:79	GCS1 expression	65:79	GCS1 expression	65:79	p32 regulates ER stress and lipid homeostasis by down-regulating GCS1 expression.
29465311	6	63	theme	Acc	1139:1141	arg1	down-regulation					1102:1116	the down-regulation	1098:1116	the down-regulation of Srebp1, Fasn, and Acc	1098:1141	We demonstrate that increased GCS1 expression alleviates fatty acid-induced ER stress and is critical for suppressing ER stress-associated lipogenic gene activation, as demonstrated by the down-regulation of Srebp1, Fasn, and Acc.
29465311	4	64	theme	acid-induced	625:636	arg1	stress					641:646	fatty acid-induced ER stress	619:646	fatty acid-induced ER stress	619:646	Here, we show that p32 promotes lipid biosynthesis by modulating fatty acid-induced ER stress.
29465311	5	65	theme	lumen-anchored	773:786	arg1	glucosidase					745:755	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I	682:757	endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1)	682:764	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	65	theme	lumen-anchored	773:786	arg1	glucosidase					788:798	an ER lumen-anchored glucosidase	767:798	an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins	767:861	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	5	65	theme	lumen-anchored	773:786	arg1	essential					808:816	essential	808:816	essential	808:816	We found that p32 interacts with endoplasmic reticulum-anchored enzyme mannosyl-oligosaccharide glucosidase I (GCS1), an ER lumen-anchored glucosidase that is essential for the processing of N-linked glycoproteins, and reduces GCS1 in a lysosome-dependent manner.
29465311	4	66	theme	fatty	619:623	arg1	stress					641:646	fatty acid-induced ER stress	619:646	fatty acid-induced ER stress	619:646	Here, we show that p32 promotes lipid biosynthesis by modulating fatty acid-induced ER stress.
29465311	1	67	theme	major	134:138	arg1	role					140:143	a major role	132:143	a major role	132:143	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
29465311	1	68	theme	nonalcoholic	226:237	arg1	disease					251:257	nonalcoholic fatty liver disease	226:257	nonalcoholic fatty liver disease	226:257	Sustained endoplasmic reticulum (ER) stress plays a major role in the development of many metabolic diseases, including cardiovascular disease, nonalcoholic fatty liver disease, insulin resistance, obesity, and diabetes.
31406333	3	0	gly	glycosylation	688:700	arg2	site					702:705	an N-linked glycosylation site	676:705	an N-linked glycosylation site	676:705	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	2	1	theme	A/Hong	525:530	arg1	strain					555:560	the A/Hong Kong/4801/2014 vaccine strain	521:560	the A/Hong Kong/4801/2014 vaccine strain	521:560	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	1	2	theme	A	143:143	arg1	virus					151:155	A(H3N2) virus	143:155	A(H3N2) virus	143:155	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	4	3	theme	A	886:886	arg1	viruses					930:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses	877:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	877:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	3	4	theme	NA	629:630	arg1	residues					632:639	NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468	629:729	NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468	629:729	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	1	5	theme	antigenic	309:317	arg1	change					319:324	antigenic change	309:324	antigenic change	309:324	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	1	6	theme	rigorous	222:229	arg1	investigation					231:243	the rigorous investigation	218:243	the rigorous investigation of haemagglutinin	218:261	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	4	7	theme	monoclonal	798:807	arg1	antibodies					809:818	some human monoclonal antibodies	787:818	some human monoclonal antibodies	787:818	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	7	theme	monoclonal	798:807	arg1	those					831:835	those	831:835	those	831:835	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	3	8	dep	introducing	664:674	arg1	S245N/S247T					651:661	S245N/S247T	651:661	S245N/S247T	651:661	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	4	9	theme	NA	764:765	arg1	result					737:742	a result	735:742	a result	735:742	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	9	theme	NA	764:765	arg1	binding					749:755	the binding	745:755	the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains,	745:977	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	7	10	theme	influenza	1353:1361	arg1	infection					1369:1377	influenza virus infection	1353:1377	influenza virus infection	1353:1377	Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
31406333	4	11	theme	human	792:796	arg1	antibodies					809:818	some human monoclonal antibodies	787:818	some human monoclonal antibodies	787:818	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	11	theme	human	792:796	arg1	those					831:835	those	831:835	those	831:835	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	6	12	from	residue	1161:1167	arg1	site					1153:1156	the glycosylation site	1135:1156	the glycosylation site at residue 245	1135:1171	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	5	13	dep	in	1076:1077	arg1	vivo					1079:1082	vivo	1079:1082	vivo	1079:1082	This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge.
31406333	0	14	from	strain	135:140	arg1	distinct					87:94	distinct	87:94	distinct	87:94	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	0	14	from	strain	135:140	arg1	neuraminidase					4:16	The neuraminidase	0:16	The neuraminidase of A(H3N2) influenza viruses circulating since 2016	0:68	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	5	15	theme	NA-antibody-based	1039:1055	arg1	protection					1057:1066	NA-antibody-based protection	1039:1066	NA-antibody-based protection against in vivo virus challenge	1039:1098	This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge.
31406333	4	16	theme	viruses	930:936	arg1	NA					871:872	the NA	867:872	the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	867:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	1	17	theme	H3N2	145:148	arg1	virus					151:155	A(H3N2) virus	143:155	A(H3N2) virus	143:155	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	2	18	theme	A	436:436	arg1	viruses					444:450	the circulating A(H3N2) viruses	420:450	the circulating A(H3N2) viruses	420:450	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	6	19	gly	glycosylation	1139:1151	arg2	site					1153:1156	the glycosylation site	1135:1156	the glycosylation site at residue 245	1135:1171	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	6	19	gly	glycosylation	1139:1151	arg2	residue					1161:1167	residue 245	1161:1171	residue 245	1161:1171	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	3	20	from	residues	632:639	arg1	mutations					616:624	amino acid mutations	605:624	amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468	605:729	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	2	21	theme	vaccine	547:553	arg1	strain					555:560	the A/Hong Kong/4801/2014 vaccine strain	521:560	the A/Hong Kong/4801/2014 vaccine strain	521:560	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	3	22	theme	acid	611:614	arg1	mutations					616:624	amino acid mutations	605:624	amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468	605:729	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	1	23	theme	haemagglutinin	248:261	arg1	investigation					231:243	the rigorous investigation	218:243	the rigorous investigation of haemagglutinin	218:261	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	2	24	theme	Kong/4801/2014	532:545	arg1	strain					555:560	the A/Hong Kong/4801/2014 vaccine strain	521:560	the A/Hong Kong/4801/2014 vaccine strain	521:560	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	7	25	theme	NA	1307:1308	arg1	drift					1320:1324	NA antigenic drift	1307:1324	NA antigenic drift	1307:1324	Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
31406333	7	26	theme	influenza	1483:1491	arg1	vaccines					1493:1500	influenza vaccines	1483:1500	influenza vaccines	1483:1500	Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
31406333	0	27	theme	A	21:21	arg1	viruses					39:45	A(H3N2) influenza viruses	21:45	A(H3N2) influenza viruses circulating since 2016	21:68	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	6	28	theme	X-ray	1101:1105	arg1	crystallography					1107:1121	X-ray crystallography	1101:1121	X-ray crystallography	1101:1121	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	0	29	theme	A/Hong	105:110	arg1	strain					135:140	the A/Hong Kong/4801/2014 vaccine strain	101:140	the A/Hong Kong/4801/2014 vaccine strain	101:140	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	7	30	theme	virus	1363:1367	arg1	infection					1369:1377	influenza virus infection	1353:1377	influenza virus infection	1353:1377	Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
31406333	7	31	theme	vaccines	1493:1500	arg1	optimization					1467:1478	the optimization	1463:1478	the optimization of influenza vaccines	1463:1500	Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
31406333	1	32	theme	recent	170:175	arg1	seasons					187:193	recent influenza seasons	170:193	recent influenza seasons	170:193	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	4	33	theme	contemporary	949:960	arg1	strains					970:976	contemporary A(H3N2) strains	949:976	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	877:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	6	34	theme	glycosylation	1139:1151	arg1	site					1153:1156	the glycosylation site	1135:1156	the glycosylation site at residue 245	1135:1171	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	4	35	theme	pandemic	921:928	arg1	viruses					930:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses	877:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	877:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	1	36	theme	influenza	177:185	arg1	seasons					187:193	recent influenza seasons	170:193	recent influenza seasons	170:193	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	6	37	theme	NA	1221:1222	arg1	site					1231:1234	the NA active site	1217:1234	the NA active site	1217:1234	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	0	38	theme	vaccine	127:133	arg1	strain					135:140	the A/Hong Kong/4801/2014 vaccine strain	101:140	the A/Hong Kong/4801/2014 vaccine strain	101:140	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	5	39	theme	in	1076:1077	arg1	challenge					1090:1098	in vivo virus challenge	1076:1098	in vivo virus challenge	1076:1098	This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge.
31406333	4	40	theme	reference	911:919	arg1	viruses					930:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses	877:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	877:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	41	theme	broad	847:851	arg1	reactivity					853:862	broad reactivity	847:862	broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	847:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	3	42	theme	glycosylation	688:700	arg1	site					702:705	an N-linked glycosylation site	676:705	an N-linked glycosylation site	676:705	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	0	43	theme	Kong/4801/2014	112:125	arg1	strain					135:140	the A/Hong Kong/4801/2014 vaccine strain	101:140	the A/Hong Kong/4801/2014 vaccine strain	101:140	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	1	44	theme	A	365:365	arg1	virus					373:377	A(H3N2) virus	365:377	A(H3N2) virus	365:377	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	4	45	theme	1957	881:884	arg1	H2N2					888:891	H2N2	888:891	H2N2	888:891	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	45	theme	1957	881:884	arg1	A					886:886	1957 A	881:886	1957 A(H2N2)	881:892	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	46	theme	strains	970:976	arg1	NA					871:872	the NA	867:872	the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	867:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	3	47	dep	247	646:648	arg1	introducing					664:674	introducing	664:674	introducing an N-linked glycosylation site at residue 245	664:720	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	0	48	theme	influenza	29:37	arg1	viruses					39:45	A(H3N2) influenza viruses	21:45	A(H3N2) influenza viruses circulating since 2016	21:68	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	3	49	dep	residues	632:639	arg1	245					641:643	245	641:643	245	641:643	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	3	49	dep	residues	632:639	arg1	468					727:729	468	727:729	468	727:729	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	3	49	dep	residues	632:639	arg1	247					646:648	247	646:648	247	646:648	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	4	50	theme	A	770:770	arg1	virus					778:782	A(H3N2) virus	770:782	A(H3N2) virus	770:782	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	3	51	theme	antigenic	568:576	arg1	drift					578:582	This antigenic drift	563:582	This antigenic drift	563:582	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	3	52	link	N-linked	679:686	arg1	site					702:705	an N-linked glycosylation site	676:705	an N-linked glycosylation site	676:705	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	2	53	theme	viruses	444:450	arg1	NA					414:415	the NA	410:415	the NA of the circulating A(H3N2) viruses	410:450	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	2	54	theme	significant	468:478	arg1	drift					490:494	significant antigenic drift	468:494	significant antigenic drift since 2016	468:505	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	1	55	theme	H3N2	367:370	arg1	virus					373:377	A(H3N2) virus	365:377	A(H3N2) virus	365:377	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	7	56	theme	antigenic	1310:1318	arg1	drift					1320:1324	NA antigenic drift	1307:1324	NA antigenic drift	1307:1324	Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
31406333	4	57	theme	1968	898:901	arg1	H3N2					905:908	H3N2	905:908	H3N2	905:908	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	57	theme	1968	898:901	arg1	A					903:903	1968 A	898:903	1968 A(H3N2)	898:909	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	3	58	theme	N-linked	679:686	arg1	site					702:705	an N-linked glycosylation site	676:705	an N-linked glycosylation site	676:705	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	4	59	theme	H3N2	772:775	arg1	virus					778:782	A(H3N2) virus	770:782	A(H3N2) virus	770:782	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	3	60	theme	amino	605:609	arg1	mutations					616:624	amino acid mutations	605:624	amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468	605:729	This antigenic drift was mainly caused by amino acid mutations at NA residues 245, 247 (S245N/S247T; introducing an N-linked glycosylation site at residue 245) and 468.
31406333	7	61	theme	NA	1426:1427	arg1	antigenicity					1429:1440	NA antigenicity	1426:1440	NA antigenicity for consideration	1426:1458	Our findings suggest that NA antigenic drift impacts protection against influenza virus infection, thus highlighting the importance of including NA antigenicity for consideration in the optimization of influenza vaccines.
31406333	2	62	theme	antigenic	480:488	arg1	drift					490:494	significant antigenic drift	468:494	significant antigenic drift since 2016	468:505	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	1	63	theme	virus	373:377	arg1	predominance					349:360	the predominance	345:360	the predominance of A(H3N2) virus	345:377	A(H3N2) virus predominated recent influenza seasons, which has resulted in the rigorous investigation of haemagglutinin, but whether neuraminidase (NA) has undergone antigenic change and contributed to the predominance of A(H3N2) virus is unknown.
31406333	4	64	theme	A	962:962	arg1	strains					970:976	contemporary A(H3N2) strains	949:976	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	877:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	5	65	theme	virus	1084:1088	arg1	challenge					1090:1098	in vivo virus challenge	1076:1098	in vivo virus challenge	1076:1098	This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge.
31406333	5	66	theme	antigenic	1010:1018	arg1	drift					1020:1024	This antigenic drift	1005:1024	This antigenic drift	1005:1024	This antigenic drift also reduced NA-antibody-based protection against in vivo virus challenge.
31406333	2	67	theme	circulating	424:434	arg1	viruses					444:450	the circulating A(H3N2) viruses	420:450	the circulating A(H3N2) viruses	420:450	Here, we show that the NA of the circulating A(H3N2) viruses has experienced significant antigenic drift since 2016 compared with the A/Hong Kong/4801/2014 vaccine strain.
31406333	4	68	theme	virus	778:782	arg1	NA					764:765	the NA	760:765	the NA of A(H3N2) virus	760:782	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	6	69	theme	conserved	1185:1193	arg1	epitope					1195:1201	a conserved epitope	1183:1201	a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding	1183:1278	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	4	70	contain	have	842:845	arg1	those					831:835	those	831:835	those	831:835	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	70	contain	have	842:845	arg2	reactivity					853:862	broad reactivity	847:862	broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	847:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	4	71	theme	A	903:903	arg1	viruses					930:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses	877:936	the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains	877:976	As a result, the binding of the NA of A(H3N2) virus by some human monoclonal antibodies, including those that have broad reactivity to the NA of the 1957 A(H2N2) and 1968 A(H3N2) reference pandemic viruses as well as contemporary A(H3N2) strains, was reduced or abolished.
31406333	0	72	theme	viruses	39:45	arg1	distinct					87:94	distinct	87:94	distinct	87:94	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	0	72	theme	viruses	39:45	arg1	neuraminidase					4:16	The neuraminidase	0:16	The neuraminidase of A(H3N2) influenza viruses circulating since 2016	0:68	The neuraminidase of A(H3N2) influenza viruses circulating since 2016 is antigenically distinct from the A/Hong Kong/4801/2014 vaccine strain.
31406333	6	73	theme	active	1224:1229	arg1	site					1231:1234	the NA active site	1217:1234	the NA active site	1217:1234	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
31406333	6	74	theme	antibody	1263:1270	arg1	binding					1272:1278	antibody binding	1263:1278	antibody binding	1263:1278	X-ray crystallography showed that the glycosylation site at residue 245 is within a conserved epitope that overlaps the NA active site, explaining why it impacts antibody binding.
28277743	6	0	theme	obese	955:959	arg1	mice					961:964	obese mice	955:964	obese mice	955:964	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	1	theme	biological	1102:1111	arg1	responses					1113:1121	other biological responses	1096:1121	other biological responses	1096:1121	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	1	theme	biological	1102:1111	arg1	decrease					1260:1267	a decrease	1258:1267	a decrease in expression of endothelial cell-cell junctional proteins	1258:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	1	theme	biological	1102:1111	arg1	increase					1197:1204	an increase	1194:1204	an increase in expression of endothelial adhesion molecules	1194:1252	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	9	2	theme	pulmonary	1927:1935	arg1	dysfunction					1954:1964	pulmonary endothelial cell dysfunction	1927:1964	pulmonary endothelial cell dysfunction	1927:1964	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	7	3	theme	ER	1526:1527	arg1	stress					1529:1534	ER stress	1526:1534	ER stress	1526:1534	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	5	4	theme	ER	705:706	arg1	kinase					708:713	protein kinase R-like ER kinase	683:713	protein kinase R-like ER kinase	683:713	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	6	5	theme	proteins	1319:1326	arg1	expression					1272:1281	expression	1272:1281	expression of endothelial cell-cell junctional proteins	1272:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	7	6	theme	ER	1464:1465	arg1	stress					1467:1472	ER stress	1464:1472	ER stress	1464:1472	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	9	7	theme	cell	1949:1952	arg1	dysfunction					1954:1964	pulmonary endothelial cell dysfunction	1927:1964	pulmonary endothelial cell dysfunction	1927:1964	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	8	8	theme	vascular	1679:1686	arg1	expression					1705:1714	vascular endothelial cell expression	1679:1714	vascular endothelial cell expression of adhesion molecules	1679:1736	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	10	9	theme	protein	1999:2005	arg1	load					2007:2010	protein load	1999:2010	protein load in the ER of pulmonary endothelial cells	1999:2051	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	6	10	theme	endothelial	1286:1296	arg1	proteins					1319:1326	endothelial cell-cell junctional proteins	1286:1326	endothelial cell-cell junctional proteins	1286:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	8	11	theme	LPS-induced	1760:1770	arg1	injury					1783:1788	LPS-induced acute lung injury	1760:1788	LPS-induced acute lung injury in diet-induced obese mice	1760:1815	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	0	12	theme	Obesity-Induced	0:14	arg1	Stress					38:43	Obesity-Induced Endoplasmic Reticulum Stress	0:43	Obesity-Induced Endoplasmic Reticulum Stress	0:43	Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.
28277743	8	13	theme	lung	1778:1781	arg1	injury					1783:1788	LPS-induced acute lung injury	1760:1788	LPS-induced acute lung injury in diet-induced obese mice	1760:1815	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	1	14	theme	distress	183:190	arg1	syndrome					192:199	acute respiratory distress syndrome	165:199	acute respiratory distress syndrome	165:199	RETRACTED: Obesity is a significant risk factor for acute respiratory distress syndrome.
28277743	6	15	theme	endothelial	915:925	arg1	cells					927:931	primary lung endothelial cells	902:931	primary lung endothelial cells	902:931	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	16	from	decrease	1260:1267	arg1	expression					1272:1281	expression	1272:1281	expression of endothelial cell-cell junctional proteins	1272:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	16	from	decrease	1260:1267	arg1	expression					1209:1218	expression	1209:1218	expression of endothelial adhesion molecules	1209:1252	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	17	theme	mice	1178:1181	arg1	endothelium					1144:1154	the lung endothelium	1135:1154	the lung endothelium of diet-induced obese mice	1135:1181	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	5	18	theme	kinase	691:696	arg1	kinase					708:713	protein kinase R-like ER kinase	683:713	protein kinase R-like ER kinase	683:713	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	19	attach	isolated	836:843	arg1	mice					869:872	diet-induced obese mice	850:872	diet-induced obese mice	850:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	19	attach	isolated	836:843	arg2	cells					830:834	primary lung endothelial cells	805:834	primary lung endothelial cells isolated from diet-induced obese mice	805:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	6	20	theme	junctional	1308:1317	arg1	proteins					1319:1326	endothelial cell-cell junctional proteins	1286:1326	endothelial cell-cell junctional proteins	1286:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	21	theme	diet-induced	1159:1170	arg1	mice					1178:1181	diet-induced obese mice	1159:1181	diet-induced obese mice	1159:1181	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	5	22	theme	activating	749:758	arg1	factor					774:779	activating transcription factor 6	749:781	activating transcription factor 6	749:781	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	8	23	theme	obese	1806:1810	arg1	mice					1812:1815	diet-induced obese mice	1793:1815	diet-induced obese mice	1793:1815	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	6	24	theme	fatty	983:987	arg1	acids					989:993	saturated fatty acids	973:993	saturated fatty acids that mimic obese serum	973:1016	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	3	25	theme	diet-induced	282:293	arg1	mice					301:304	diet-induced obese mice	282:304	diet-induced obese mice	282:304	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	10	26	theme	cells	2047:2051	arg1	ER					2019:2020	the ER	2015:2020	the ER of pulmonary endothelial cells	2015:2051	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	4	27	from	dysfunction	484:494	arg1	mice					518:521	diet-induced obese mice	499:521	diet-induced obese mice	499:521	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	3	28	theme	endothelial	333:343	arg1	dysfunction					345:355	pulmonary vascular endothelial dysfunction	314:355	pulmonary vascular endothelial dysfunction	314:355	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	4	29	theme	diet-induced	499:510	arg1	mice					518:521	diet-induced obese mice	499:521	diet-induced obese mice	499:521	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	6	30	theme	molecules	1244:1252	arg1	expression					1209:1218	expression	1209:1218	expression of endothelial adhesion molecules	1209:1252	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	10	31	theme	pulmonary	2025:2033	arg1	cells					2047:2051	pulmonary endothelial cells	2025:2051	pulmonary endothelial cells	2025:2051	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	5	32	theme	enzyme	735:740	arg1	α					742:742	inositol-requiring enzyme α	716:742	inositol-requiring enzyme α	716:742	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	8	33	with	Treatment	1580:1588	arg1	chaperone					1636:1644	a chemical protein chaperone	1617:1644	a chemical protein chaperone that reduces ER stress	1617:1667	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	33	with	Treatment	1580:1588	arg1	acid					1611:1614	4-phenylbutyric acid	1595:1614	4-phenylbutyric acid	1595:1614	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	3	34	theme	pulmonary	314:322	arg1	dysfunction					345:355	pulmonary vascular endothelial dysfunction	314:355	pulmonary vascular endothelial dysfunction	314:355	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	6	35	theme	endothelial	1223:1233	arg1	molecules					1244:1252	endothelial adhesion molecules	1223:1252	endothelial adhesion molecules	1223:1252	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	10	36	theme	acute	2075:2079	arg1	syndrome					2102:2109	acute respiratory distress syndrome	2075:2109	acute respiratory distress syndrome in obese individuals	2075:2130	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	1	37	theme	significant	137:147	arg1	factor					154:159	a significant risk factor	135:159	a significant risk factor for acute respiratory distress syndrome	135:199	RETRACTED: Obesity is a significant risk factor for acute respiratory distress syndrome.
28277743	1	37	theme	significant	137:147	arg1	Obesity					124:130	Obesity	124:130	Obesity	124:130	RETRACTED: Obesity is a significant risk factor for acute respiratory distress syndrome.
28277743	4	38	theme	lung	467:470	arg1	dysfunction					484:494	lung endothelial dysfunction	467:494	lung endothelial dysfunction in diet-induced obese mice	467:521	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	4	39	theme	endoplasmic	548:558	arg1	reticulum					560:568	endoplasmic reticulum	548:568	increased endoplasmic reticulum (ER) stress	538:580	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	4	39	theme	endoplasmic	548:558	arg1	ER					571:572	ER	571:572	ER	571:572	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	0	40	theme	Acute	94:98	arg1	Injury					105:110	Acute Lung Injury	94:110	Acute Lung Injury	94:110	Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.
28277743	10	41	from	load	2007:2010	arg1	ER					2019:2020	the ER	2015:2020	the ER of pulmonary endothelial cells	2015:2051	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	5	42	theme	sensors	642:648	arg1	expression					618:627	enhanced expression	609:627	enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice	609:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	1	43	theme	acute	165:169	arg1	syndrome					192:199	acute respiratory distress syndrome	165:199	acute respiratory distress syndrome	165:199	RETRACTED: Obesity is a significant risk factor for acute respiratory distress syndrome.
28277743	10	44	theme	distress	2093:2100	arg1	syndrome					2102:2109	acute respiratory distress syndrome	2075:2109	acute respiratory distress syndrome in obese individuals	2075:2130	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	5	45	theme	misfolded	653:661	arg1	α					742:742	inositol-requiring enzyme α	716:742	inositol-requiring enzyme α	716:742	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	45	theme	misfolded	653:661	arg1	factor					774:779	activating transcription factor 6	749:781	activating transcription factor 6	749:781	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	45	theme	misfolded	653:661	arg1	kinase					708:713	protein kinase R-like ER kinase	683:713	protein kinase R-like ER kinase	683:713	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	45	theme	misfolded	653:661	arg1	proteins					663:670	misfolded proteins	653:670	misfolded proteins	653:670	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	6	46	theme	obese	1006:1010	arg1	serum					1012:1016	obese serum	1006:1016	obese serum	1006:1016	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	9	47	theme	fatty	1842:1846	arg1	acids					1848:1852	fatty acids	1842:1852	fatty acids in obese serum	1842:1867	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	5	48	theme	whole	787:791	arg1	lung					793:796	whole lung	787:796	whole lung	787:796	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	0	49	theme	Lung	52:55	arg1	Dysfunction					69:79	Lung Endothelial Dysfunction	52:79	Lung Endothelial Dysfunction	52:79	Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.
28277743	7	50	theme	endothelial	1367:1377	arg1	cells					1379:1383	lung endothelial cells	1362:1383	lung endothelial cells	1362:1383	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	3	51	theme	lung	428:431	arg1	injury					433:438	LPS-induced acute lung injury	410:438	LPS-induced acute lung injury	410:438	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	5	52	theme	diet-induced	850:861	arg1	mice					869:872	diet-induced obese mice	850:872	diet-induced obese mice	850:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	9	53	from	acids	1848:1852	arg1	serum					1863:1867	obese serum	1857:1867	obese serum	1857:1867	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	3	54	theme	LPS-induced	410:420	arg1	injury					433:438	LPS-induced acute lung injury	410:438	LPS-induced acute lung injury	410:438	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	0	55	theme	Reticulum	28:36	arg1	Stress					38:43	Obesity-Induced Endoplasmic Reticulum Stress	0:43	Obesity-Induced Endoplasmic Reticulum Stress	0:43	Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.
28277743	6	56	theme	lung	910:913	arg1	cells					927:931	primary lung endothelial cells	902:931	primary lung endothelial cells	902:931	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	57	theme	ER	1065:1066	arg1	stress					1068:1073	ER stress	1065:1073	ER stress	1065:1073	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	9	58	theme	ER	1876:1877	arg1	stress					1879:1884	ER stress	1876:1884	ER stress	1876:1884	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	8	59	theme	4-phenylbutyric	1595:1609	arg1	chaperone					1636:1644	a chemical protein chaperone	1617:1644	a chemical protein chaperone that reduces ER stress	1617:1667	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	59	theme	4-phenylbutyric	1595:1609	arg1	acid					1611:1614	4-phenylbutyric acid	1595:1614	4-phenylbutyric acid	1595:1614	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	5	60	theme	endothelial	818:828	arg1	cells					830:834	primary lung endothelial cells	805:834	primary lung endothelial cells isolated from diet-induced obese mice	805:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	7	61	theme	Similar	1329:1335	arg1	changes					1337:1343	Similar changes	1329:1343	Similar changes	1329:1343	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	0	62	theme	Endothelial	57:67	arg1	Dysfunction					69:79	Lung Endothelial Dysfunction	52:79	Lung Endothelial Dysfunction	52:79	Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.
28277743	7	63	theme	endothelial	1543:1553	arg1	dysfunction					1555:1565	endothelial dysfunction	1543:1565	endothelial dysfunction	1543:1565	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	6	64	theme	lung	1139:1142	arg1	endothelium					1144:1154	the lung endothelium	1135:1154	the lung endothelium of diet-induced obese mice	1135:1181	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	9	65	theme	pulmonary	1893:1901	arg1	endothelium					1903:1913	the pulmonary endothelium	1889:1913	the pulmonary endothelium	1889:1913	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	8	66	theme	chemical	1619:1626	arg1	chaperone					1636:1644	a chemical protein chaperone	1617:1644	a chemical protein chaperone that reduces ER stress	1617:1667	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	66	theme	chemical	1619:1626	arg1	acid					1611:1614	4-phenylbutyric acid	1595:1614	4-phenylbutyric acid	1595:1614	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	67	theme	endothelial	1688:1698	arg1	expression					1705:1714	vascular endothelial cell expression	1679:1714	vascular endothelial cell expression of adhesion molecules	1679:1736	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	10	68	from	syndrome	2102:2109	arg1	individuals					2120:2130	obese individuals	2114:2130	obese individuals	2114:2130	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	6	69	theme	markers	1054:1060	arg1	induction					1083:1091	the induction	1079:1091	the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins	1079:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	69	theme	markers	1054:1060	arg1	expression					1040:1049	enhanced expression	1031:1049	enhanced expression of markers of ER stress	1031:1073	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	70	theme	responses	1113:1121	arg1	induction					1083:1091	the induction	1079:1091	the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins	1079:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	70	theme	responses	1113:1121	arg1	expression					1040:1049	enhanced expression	1031:1049	enhanced expression of markers of ER stress	1031:1073	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	71	from	mice	961:964	arg1	serum					944:948	serum	944:948	serum from obese mice	944:964	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	5	72	theme	R-like	698:703	arg1	kinase					708:713	protein kinase R-like ER kinase	683:713	protein kinase R-like ER kinase	683:713	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	8	73	theme	adhesion	1719:1726	arg1	molecules					1728:1736	adhesion molecules	1719:1736	adhesion molecules	1719:1736	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	6	74	theme	other	1096:1100	arg1	responses					1113:1121	other biological responses	1096:1121	other biological responses	1096:1121	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	74	theme	other	1096:1100	arg1	decrease					1260:1267	a decrease	1258:1267	a decrease in expression of endothelial cell-cell junctional proteins	1258:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	74	theme	other	1096:1100	arg1	increase					1197:1204	an increase	1194:1204	an increase in expression of endothelial adhesion molecules	1194:1252	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	9	75	theme	endothelial	1937:1947	arg1	dysfunction					1954:1964	pulmonary endothelial cell dysfunction	1927:1964	pulmonary endothelial cell dysfunction	1927:1964	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	6	76	theme	cell-cell	1298:1306	arg1	proteins					1319:1326	endothelial cell-cell junctional proteins	1286:1326	endothelial cell-cell junctional proteins	1286:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	7	77	theme	N-linked	1486:1493	arg1	glycosylation					1495:1507	N-linked glycosylation	1486:1507	N-linked glycosylation	1486:1507	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	1	78	theme	respiratory	171:181	arg1	syndrome					192:199	acute respiratory distress syndrome	165:199	acute respiratory distress syndrome	165:199	RETRACTED: Obesity is a significant risk factor for acute respiratory distress syndrome.
28277743	7	79	link	N-linked	1486:1493	arg1	glycosylation					1495:1507	N-linked glycosylation	1486:1507	N-linked glycosylation	1486:1507	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	5	80	theme	primary	805:811	arg1	cells					830:834	primary lung endothelial cells	805:834	primary lung endothelial cells isolated from diet-induced obese mice	805:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	81	theme	protein	683:689	arg1	kinase					708:713	protein kinase R-like ER kinase	683:713	protein kinase R-like ER kinase	683:713	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	8	82	theme	acute	1772:1776	arg1	injury					1783:1788	LPS-induced acute lung injury	1760:1788	LPS-induced acute lung injury in diet-induced obese mice	1760:1815	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	6	83	theme	obese	1172:1176	arg1	mice					1178:1181	diet-induced obese mice	1159:1181	diet-induced obese mice	1159:1181	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	5	84	theme	transcription	760:772	arg1	factor					774:779	activating transcription factor 6	749:781	activating transcription factor 6	749:781	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	8	85	theme	diet-induced	1793:1804	arg1	mice					1812:1815	diet-induced obese mice	1793:1815	diet-induced obese mice	1793:1815	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	6	86	theme	saturated	973:981	arg1	acids					989:993	saturated fatty acids	973:993	saturated fatty acids that mimic obese serum	973:1016	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	3	87	theme	obese	295:299	arg1	mice					301:304	diet-induced obese mice	282:304	diet-induced obese mice	282:304	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	4	88	theme	obese	512:516	arg1	mice					518:521	diet-induced obese mice	499:521	diet-induced obese mice	499:521	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	10	89	theme	endothelial	2035:2045	arg1	cells					2047:2051	pulmonary endothelial cells	2025:2051	pulmonary endothelial cells	2025:2051	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	5	90	theme	inositol-requiring	716:733	arg1	α					742:742	inositol-requiring enzyme α	716:742	inositol-requiring enzyme α	716:742	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	6	91	theme	adhesion	1235:1242	arg1	molecules					1244:1252	endothelial adhesion molecules	1223:1252	endothelial adhesion molecules	1223:1252	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	5	92	theme	enhanced	609:616	arg1	expression					618:627	enhanced expression	609:627	enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice	609:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	93	from	expression	618:627	arg1	cells					830:834	primary lung endothelial cells	805:834	primary lung endothelial cells isolated from diet-induced obese mice	805:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	93	from	expression	618:627	arg1	lung					793:796	whole lung	787:796	whole lung	787:796	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	3	94	theme	vascular	324:331	arg1	dysfunction					345:355	pulmonary vascular endothelial dysfunction	314:355	pulmonary vascular endothelial dysfunction	314:355	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	4	95	theme	endothelial	472:482	arg1	dysfunction					484:494	lung endothelial dysfunction	467:494	lung endothelial dysfunction in diet-induced obese mice	467:521	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	7	96	theme	whole-lung	1392:1401	arg1	tissue					1403:1408	whole-lung tissue	1392:1408	whole-lung tissue	1392:1408	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	7	97	located	observed	1350:1357	arg1	cells					1379:1383	lung endothelial cells	1362:1383	lung endothelial cells	1362:1383	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	7	97	located	observed	1350:1357	arg2	changes					1337:1343	Similar changes	1329:1343	Similar changes	1329:1343	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	1	98	theme	risk	149:152	arg1	factor					154:159	a significant risk factor	135:159	a significant risk factor for acute respiratory distress syndrome	135:199	RETRACTED: Obesity is a significant risk factor for acute respiratory distress syndrome.
28277743	1	98	theme	risk	149:152	arg1	Obesity					124:130	Obesity	124:130	Obesity	124:130	RETRACTED: Obesity is a significant risk factor for acute respiratory distress syndrome.
28277743	6	99	theme	enhanced	1031:1038	arg1	expression					1040:1049	enhanced expression	1031:1049	enhanced expression of markers of ER stress	1031:1073	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	4	100	theme	reticulum	560:568	arg1	stress					575:580	increased endoplasmic reticulum (ER) stress	538:580	increased endoplasmic reticulum (ER) stress	538:580	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	0	101	theme	Lung	100:103	arg1	Injury					105:110	Acute Lung Injury	94:110	Acute Lung Injury	94:110	Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.
28277743	10	102	theme	respiratory	2081:2091	arg1	syndrome					2102:2109	acute respiratory distress syndrome	2075:2109	acute respiratory distress syndrome in obese individuals	2075:2130	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	5	103	theme	proteins	663:670	arg1	sensors					642:648	the major sensors	632:648	the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6,	632:782	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	7	104	theme	lung	1362:1365	arg1	cells					1379:1383	lung endothelial cells	1362:1383	lung endothelial cells	1362:1383	Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung.
28277743	3	105	theme	enhanced	383:390	arg1	susceptibility					392:405	enhanced susceptibility	383:405	enhanced susceptibility to LPS-induced acute lung injury	383:438	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	4	106	theme	increased	538:546	arg1	stress					575:580	increased endoplasmic reticulum (ER) stress	538:580	increased endoplasmic reticulum (ER) stress	538:580	Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress.
28277743	6	107	from	increase	1197:1204	arg1	expression					1272:1281	expression	1272:1281	expression of endothelial cell-cell junctional proteins	1272:1326	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	6	107	from	increase	1197:1204	arg1	expression					1209:1218	expression	1209:1218	expression of endothelial adhesion molecules	1209:1252	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	0	108	theme	Endoplasmic	16:26	arg1	Stress					38:43	Obesity-Induced Endoplasmic Reticulum Stress	0:43	Obesity-Induced Endoplasmic Reticulum Stress	0:43	Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.
28277743	9	109	theme	obese	1857:1861	arg1	serum					1863:1867	obese serum	1857:1867	obese serum	1857:1867	Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction.
28277743	5	110	theme	obese	863:867	arg1	mice					869:872	diet-induced obese mice	850:872	diet-induced obese mice	850:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	5	111	theme	major	636:640	arg1	sensors					642:648	the major sensors	632:648	the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6,	632:782	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	6	112	theme	stress	1068:1073	arg1	markers					1054:1060	markers	1054:1060	markers of ER stress	1054:1073	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	3	113	theme	acute	422:426	arg1	injury					433:438	LPS-induced acute lung injury	410:438	LPS-induced acute lung injury	410:438	We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury.
28277743	5	114	theme	lung	813:816	arg1	cells					830:834	primary lung endothelial cells	805:834	primary lung endothelial cells isolated from diet-induced obese mice	805:872	Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice.
28277743	6	115	theme	primary	902:908	arg1	cells					927:931	primary lung endothelial cells	902:931	primary lung endothelial cells	902:931	Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins.
28277743	8	116	theme	protein	1628:1634	arg1	chaperone					1636:1644	a chemical protein chaperone	1617:1644	a chemical protein chaperone that reduces ER stress	1617:1667	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	116	theme	protein	1628:1634	arg1	acid					1611:1614	4-phenylbutyric acid	1595:1614	4-phenylbutyric acid	1595:1614	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	117	theme	cell	1700:1703	arg1	expression					1705:1714	vascular endothelial cell expression	1679:1714	vascular endothelial cell expression of adhesion molecules	1679:1736	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	10	118	theme	obese	2114:2118	arg1	individuals					2120:2130	obese individuals	2114:2130	obese individuals	2114:2130	Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese individuals.
28277743	8	119	theme	ER	1659:1660	arg1	stress					1662:1667	ER stress	1659:1667	ER stress	1659:1667	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	120	from	injury	1783:1788	arg1	mice					1812:1815	diet-induced obese mice	1793:1815	diet-induced obese mice	1793:1815	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
28277743	8	121	theme	molecules	1728:1736	arg1	expression					1705:1714	vascular endothelial cell expression	1679:1714	vascular endothelial cell expression of adhesion molecules	1679:1736	Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice.
31425910	7	0	theme	fluorous	1628:1635	arg1	segment					1637:1643	the fluorous segment	1624:1643	the fluorous segment	1624:1643	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	4	1	theme	glycomimetic	984:995	arg1	moiety					997:1002	a sp2-iminosugar glycomimetic moiety	967:1002	a sp2-iminosugar glycomimetic moiety	967:1002	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	8	2	theme	Biochemical	1849:1859	arg1	data					1879:1882	Biochemical and computational data	1849:1882	Biochemical and computational data	1849:1882	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	5	3	theme	master	1342:1347	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	3	theme	master	1342:1347	arg1	MAPK					1391:1394	p38 MAPK	1387:1394	p38 MAPK	1387:1394	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	9	4	theme	of	2074:2075	arg1	results					2077:2083	The ensemble of results	2061:2083	The ensemble of results	2061:2083	The ensemble of results provide a proof of concept of the potential of sp2-IGLs as immunoregulators.
31425910	8	5	theme	autophosphorylation	2034:2052	arg1	route					2054:2058	the noncanonical autophosphorylation route	2017:2058	the noncanonical autophosphorylation route	2017:2058	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	8	6	theme	computational	1865:1877	arg1	data					1879:1882	Biochemical and computational data	1849:1882	Biochemical and computational data	1849:1882	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	0	7	theme	anti-inflammatory	149:165	arg1	therapies					167:175	anti-tumor, anti-leishmanial and anti-inflammatory therapies	116:175	anti-tumor, anti-leishmanial and anti-inflammatory therapies	116:175	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	9	8	theme	concept	2104:2110	arg1	proof					2095:2099	a proof	2093:2099	a proof of concept of the potential of sp2-IGLs as immunoregulators	2093:2159	The ensemble of results provide a proof of concept of the potential of sp2-IGLs as immunoregulators.
31425910	3	9	theme	drug	879:882	arg1	strategies					897:906	drug optimization strategies	879:906	drug optimization strategies	879:906	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	3	10	theme	cytokine	664:671	arg1	capabilities					692:703	narrower cytokine secretion-inducing capabilities	655:703	narrower cytokine secretion-inducing capabilities	655:703	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	4	11	theme	N-linked	1021:1028	arg1	sp2-IGLs					1058:1065	sp2-IGLs	1058:1065	sp2-IGLs	1058:1065	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	4	11	theme	N-linked	1021:1028	arg1	glycolipids					1045:1055	N-linked sp2-iminosugar glycolipids	1021:1055	N-linked sp2-iminosugar glycolipids (sp2-IGLs)	1021:1066	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	7	12	theme	membrane-crossing	1742:1758	arg1	properties					1760:1769	membrane-crossing properties	1742:1769	membrane-crossing properties	1742:1769	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	1	13	theme	Immunomodulatory	178:193	arg1	glycolipids					195:205	Immunomodulatory glycolipids	178:205	Immunomodulatory glycolipids	178:205	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	7	14	dep	found	1649:1653	arg1	whereas					1772:1778	whereas	1772:1778	whereas	1772:1778	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	0	15	theme	polyfluoroalkyl	13:27	arg1	glycolipids					44:54	polyfluoroalkyl sp2-iminosugar glycolipids	13:54	polyfluoroalkyl sp2-iminosugar glycolipids	13:54	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	8	16	theme	allosteric	1946:1955	arg1	site					1971:1974	the allosteric lipid binding site	1942:1974	the allosteric lipid binding site of p38 MAPK	1942:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	8	16	theme	allosteric	1946:1955	arg1	MAPK					1983:1986	p38 MAPK	1979:1986	p38 MAPK	1979:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	1	17	theme	conditions	329:338	arg1	conditions					329:338	conditions	329:338	conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases	329:416	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	1	17	theme	conditions	329:338	arg1	variety					318:324	a variety	316:324	a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases	316:416	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	0	18	theme	properties	97:106	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids	0:54	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	0	18	theme	properties	97:106	arg1	evaluation					60:69	evaluation	60:69	evaluation of their immunomodulatory properties	60:106	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	5	19	theme	lengths	1272:1278	arg1	segments					1253:1260	polyfluoroalkyl segments	1237:1260	polyfluoroalkyl segments of varied lengths	1237:1278	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	8	20	theme	binding	1963:1969	arg1	site					1971:1974	the allosteric lipid binding site	1942:1974	the allosteric lipid binding site of p38 MAPK	1942:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	8	20	theme	binding	1963:1969	arg1	MAPK					1983:1986	p38 MAPK	1979:1986	p38 MAPK	1979:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	0	21	theme	anti-tumor	116:125	arg1	therapies					167:175	anti-tumor, anti-leishmanial and anti-inflammatory therapies	116:175	anti-tumor, anti-leishmanial and anti-inflammatory therapies	116:175	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	5	22	theme	cell-context	1442:1453	arg1	manner					1465:1470	a cell-context dependent manner	1440:1470	a cell-context dependent manner	1440:1470	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	0	23	theme	anti-leishmanial	128:143	arg1	therapies					167:175	anti-tumor, anti-leishmanial and anti-inflammatory therapies	116:175	anti-tumor, anti-leishmanial and anti-inflammatory therapies	116:175	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	5	24	theme	polyfluoroalkyl	1237:1251	arg1	segments					1253:1260	polyfluoroalkyl segments	1237:1260	polyfluoroalkyl segments of varied lengths	1237:1278	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	8	25	theme	MAPK	1983:1986	arg1	site					1971:1974	the allosteric lipid binding site	1942:1974	the allosteric lipid binding site of p38 MAPK	1942:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	8	25	theme	MAPK	1983:1986	arg1	MAPK					1983:1986	p38 MAPK	1979:1986	p38 MAPK	1979:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	4	26	theme	glycosidation	1149:1161	arg1	promotors					1163:1171	glycosidation promotors	1149:1171	glycosidation promotors	1149:1171	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	8	27	theme	subsequent	1992:2001	arg1	activation					2003:2012	subsequent activation	1992:2012	subsequent activation of the noncanonical autophosphorylation route	1992:2058	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	5	28	theme	immune	1421:1426	arg1	response					1428:1435	the immune response	1417:1435	the immune response	1417:1435	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	6	29	theme	anti-inflammatory	1557:1573	arg1	activities					1575:1584	their antiproliferative, anti-leishmanial and anti-inflammatory activities	1511:1584	their antiproliferative, anti-leishmanial and anti-inflammatory activities	1511:1584	The compounds have been evaluated for their antiproliferative, anti-leishmanial and anti-inflammatory activities in different cell assays.
31425910	5	30	theme	lipid	1316:1320	arg1	site					1330:1333	the lipid binding site	1312:1333	the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK)	1312:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	30	theme	lipid	1316:1320	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	6	31	theme	anti-leishmanial	1536:1551	arg1	activities					1575:1584	their antiproliferative, anti-leishmanial and anti-inflammatory activities	1511:1584	their antiproliferative, anti-leishmanial and anti-inflammatory activities	1511:1584	The compounds have been evaluated for their antiproliferative, anti-leishmanial and anti-inflammatory activities in different cell assays.
31425910	0	32	theme	glycolipids	44:54	arg1	Synthesis					0:8	Synthesis	0:8	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids	0:54	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	0	32	theme	glycolipids	44:54	arg1	evaluation					60:69	evaluation	60:69	evaluation of their immunomodulatory properties	60:106	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	6	33	theme	antiproliferative	1517:1533	arg1	activities					1575:1584	their antiproliferative, anti-leishmanial and anti-inflammatory activities	1511:1584	their antiproliferative, anti-leishmanial and anti-inflammatory activities	1511:1584	The compounds have been evaluated for their antiproliferative, anti-leishmanial and anti-inflammatory activities in different cell assays.
31425910	4	34	with	step	1107:1110	arg1	need					1120:1123	no need	1117:1123	no need of protecting groups or glycosidation promotors	1117:1171	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	3	35	theme	stereochemical	764:777	arg1	outcome					779:785	the stereochemical outcome	760:785	the stereochemical outcome in glycosidation reactions	760:812	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	5	36	theme	p38	1349:1351	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	36	theme	p38	1349:1351	arg1	MAPK					1391:1394	p38 MAPK	1387:1394	p38 MAPK	1387:1394	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	7	37	theme	segment	1637:1643	arg1	critical					1661:1668	critical	1661:1668	critical	1661:1668	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	7	37	theme	segment	1637:1643	arg1	size					1616:1619	The size	1612:1619	The size of the fluorous segment	1612:1643	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	2	38	theme	main	421:424	arg1	difficulty					426:435	A main difficulty	419:435	A main difficulty for those channels	419:454	A main difficulty for those channels is that they often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response.
31425910	5	39	theme	activated	1361:1369	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	39	theme	activated	1361:1369	arg1	MAPK					1391:1394	p38 MAPK	1387:1394	p38 MAPK	1387:1394	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	1	40	theme	therapeutic	291:301	arg1	potential					303:311	strong therapeutic potential	284:311	strong therapeutic potential	284:311	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	5	41	theme	varied	1265:1270	arg1	lengths					1272:1278	varied lengths	1265:1278	varied lengths	1265:1278	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	4	42	theme	sp2-iminosugar	969:982	arg1	moiety					997:1002	a sp2-iminosugar glycomimetic moiety	967:1002	a sp2-iminosugar glycomimetic moiety	967:1002	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	8	43	theme	noncanonical	2021:2032	arg1	route					2054:2058	the noncanonical autophosphorylation route	2017:2058	the noncanonical autophosphorylation route	2017:2058	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	6	44	theme	cell	1599:1602	arg1	assays					1604:1609	different cell assays	1589:1609	different cell assays	1589:1609	The compounds have been evaluated for their antiproliferative, anti-leishmanial and anti-inflammatory activities in different cell assays.
31425910	4	45	from	α-stereocontrol	1079:1093	arg1	step					1107:1110	a single step	1098:1110	a single step with no need of protecting groups or glycosidation promotors	1098:1171	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	9	46	theme	ensemble	2065:2072	arg1	results					2077:2083	The ensemble of results	2061:2083	The ensemble of results	2061:2083	The ensemble of results provide a proof of concept of the potential of sp2-IGLs as immunoregulators.
31425910	4	47	link	N-linked	1021:1028	arg1	sp2-IGLs					1058:1065	sp2-IGLs	1058:1065	sp2-IGLs	1058:1065	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	4	47	link	N-linked	1021:1028	arg1	glycolipids					1045:1055	N-linked sp2-iminosugar glycolipids	1021:1055	N-linked sp2-iminosugar glycolipids (sp2-IGLs)	1021:1066	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	8	48	theme	route	2054:2058	arg1	activation					2003:2012	subsequent activation	1992:2012	subsequent activation of the noncanonical autophosphorylation route	1992:2058	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	8	48	theme	route	2054:2058	arg1	binding					1931:1937	binding	1931:1937	binding to the allosteric lipid binding site of p38 MAPK	1931:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	4	49	theme	monosaccharide	941:954	arg1	glycone					956:962	the monosaccharide glycone	937:962	the monosaccharide glycone	937:962	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	7	50	theme	hydroxylation	1784:1796	arg1	relevant					1839:1846	relevant	1839:1846	relevant	1839:1846	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	7	50	theme	hydroxylation	1784:1796	arg1	profile					1798:1804	the hydroxylation profile	1780:1804	the hydroxylation profile (gluco or galacto-like)	1780:1828	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	2	51	theme	immune	606:611	arg1	response					613:620	the immune response	602:620	the immune response	602:620	A main difficulty for those channels is that they often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response.
31425910	3	52	from	outcome	779:785	arg1	reactions					804:812	glycosidation reactions	790:812	glycosidation reactions	790:812	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	3	53	theme	narrower	655:662	arg1	capabilities					692:703	narrower cytokine secretion-inducing capabilities	655:703	narrower cytokine secretion-inducing capabilities	655:703	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	1	54	theme	iconic	257:262	arg1	α-galactosylceramide					220:239	α-galactosylceramide (KRN7000)	220:249	α-galactosylceramide (KRN7000)	220:249	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	1	54	theme	iconic	257:262	arg1	example					264:270	an iconic example	254:270	an iconic example	254:270	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	3	55	theme	optimization	884:895	arg1	strategies					897:906	drug optimization strategies	879:906	drug optimization strategies	879:906	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	3	56	theme	analogues	640:648	arg1	synthesis					627:635	The synthesis	623:635	The synthesis of analogues with narrower cytokine secretion-inducing capabilities	623:703	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	7	57	dep	profile	1798:1804	arg1	galacto-like					1816:1827	galacto-like	1816:1827	galacto-like	1816:1827	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	7	57	dep	profile	1798:1804	arg1	gluco					1807:1811	gluco	1807:1811	gluco	1807:1811	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	9	58	theme	potential	2119:2127	arg1	concept					2104:2110	concept	2104:2110	concept of the potential of sp2-IGLs as immunoregulators	2104:2159	The ensemble of results provide a proof of concept of the potential of sp2-IGLs as immunoregulators.
31425910	5	59	theme	lipid	1178:1182	arg1	tail					1184:1187	The lipid tail	1174:1187	The lipid tail	1174:1187	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	8	60	theme	action	1915:1920	arg1	mechanism					1902:1910	a mechanism	1900:1910	a mechanism of action	1900:1920	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	4	61	theme	sp2-iminosugar	1030:1043	arg1	sp2-IGLs					1058:1065	sp2-IGLs	1058:1065	sp2-IGLs	1058:1065	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	4	61	theme	sp2-iminosugar	1030:1043	arg1	glycolipids					1045:1055	N-linked sp2-iminosugar glycolipids	1021:1055	N-linked sp2-iminosugar glycolipids (sp2-IGLs)	1021:1066	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	9	62	theme	sp2-IGLs	2132:2139	arg1	potential					2119:2127	the potential	2115:2127	the potential of sp2-IGLs as immunoregulators	2115:2159	The ensemble of results provide a proof of concept of the potential of sp2-IGLs as immunoregulators.
31425910	0	63	theme	immunomodulatory	80:95	arg1	properties					97:106	their immunomodulatory properties	74:106	their immunomodulatory properties	74:106	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	3	64	theme	secretion-inducing	673:690	arg1	capabilities					692:703	narrower cytokine secretion-inducing capabilities	655:703	narrower cytokine secretion-inducing capabilities	655:703	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	4	65	theme	single	1100:1105	arg1	step					1107:1110	a single step	1098:1110	a single step with no need of protecting groups or glycosidation promotors	1098:1171	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	5	66	theme	kinase	1379:1384	arg1	site					1330:1333	the lipid binding site	1312:1333	the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK)	1312:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	66	theme	kinase	1379:1384	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	1	67	theme	autoimmune	377:386	arg1	diseases					409:416	autoimmune or neurodegenerative diseases	377:416	autoimmune or neurodegenerative diseases	377:416	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	2	68	theme	anti-inflammatory	525:541	arg1	mediators					543:551	both pro- and anti-inflammatory mediators	511:551	both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response	511:620	A main difficulty for those channels is that they often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response.
31425910	5	69	theme	p38	1387:1389	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	69	theme	p38	1387:1389	arg1	MAPK					1391:1394	p38 MAPK	1387:1394	p38 MAPK	1387:1394	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	3	70	with	analogues	640:648	arg1	capabilities					692:703	narrower cytokine secretion-inducing capabilities	655:703	narrower cytokine secretion-inducing capabilities	655:703	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	1	71	theme	neurodegenerative	391:407	arg1	diseases					409:416	autoimmune or neurodegenerative diseases	377:416	autoimmune or neurodegenerative diseases	377:416	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	8	72	theme	lipid	1957:1961	arg1	site					1971:1974	the allosteric lipid binding site	1942:1974	the allosteric lipid binding site of p38 MAPK	1942:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	8	72	theme	lipid	1957:1961	arg1	MAPK					1983:1986	p38 MAPK	1979:1986	p38 MAPK	1979:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	7	73	theme	biological	1678:1687	arg1	activity					1689:1696	the biological activity	1674:1696	the biological activity	1674:1696	The size of the fluorous segment was found to be critical for the biological activity, probably by regulating the aggregation and membrane-crossing properties, whereas the hydroxylation profile (gluco or galacto-like) was less relevant.
31425910	4	74	theme	total	1073:1077	arg1	α-stereocontrol					1079:1093	total α-stereocontrol	1073:1093	total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors	1073:1171	Here we show that replacing the monosaccharide glycone by a sp2-iminosugar glycomimetic moiety allows accessing N-linked sp2-iminosugar glycolipids (sp2-IGLs) with total α-stereocontrol in a single step with no need of protecting groups or glycosidation promotors.
31425910	5	75	theme	dependent	1455:1463	arg1	manner					1465:1470	a cell-context dependent manner	1440:1470	a cell-context dependent manner	1440:1470	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	6	76	theme	different	1589:1597	arg1	assays					1604:1609	different cell assays	1589:1609	different cell assays	1589:1609	The compounds have been evaluated for their antiproliferative, anti-leishmanial and anti-inflammatory activities in different cell assays.
31425910	8	77	theme	p38	1979:1981	arg1	MAPK					1983:1986	p38 MAPK	1979:1986	p38 MAPK	1979:1986	Biochemical and computational data further support a mechanism of action implying binding to the allosteric lipid binding site of p38 MAPK and subsequent activation of the noncanonical autophosphorylation route.
31425910	2	78	theme	cytokine	485:492	arg1	storm					494:498	a cytokine storm	483:498	a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response	483:620	A main difficulty for those channels is that they often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response.
31425910	0	79	theme	sp2-iminosugar	29:42	arg1	glycolipids					44:54	polyfluoroalkyl sp2-iminosugar glycolipids	13:54	polyfluoroalkyl sp2-iminosugar glycolipids	13:54	Synthesis of polyfluoroalkyl sp2-iminosugar glycolipids and evaluation of their immunomodulatory properties towards anti-tumor, anti-leishmanial and anti-inflammatory therapies.
31425910	3	80	theme	intrinsic	724:732	arg1	difficulty					734:743	the intrinsic difficulty	720:743	the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions	720:812	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	5	81	theme	binding	1322:1328	arg1	site					1330:1333	the lipid binding site	1312:1333	the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK)	1312:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	81	theme	binding	1322:1328	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	2	82	theme	pro-	516:519	arg1	mediators					543:551	both pro- and anti-inflammatory mediators	511:551	both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response	511:620	A main difficulty for those channels is that they often provoke a cytokine storm comprising both pro- and anti-inflammatory mediators that antagonize each other and negatively affect the immune response.
31425910	5	83	theme	mitogen	1353:1359	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	83	theme	mitogen	1353:1359	arg1	MAPK					1391:1394	p38 MAPK	1387:1394	p38 MAPK	1387:1394	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	3	84	theme	glycosidation	790:802	arg1	reactions					804:812	glycosidation reactions	790:812	glycosidation reactions	790:812	The synthesis of analogues with narrower cytokine secretion-inducing capabilities is hampered by the intrinsic difficulty at controlling the stereochemical outcome in glycosidation reactions, particularly if targeting the α-anomer, which seriously hampers drug optimization strategies.
31425910	1	85	theme	strong	284:289	arg1	potential					303:311	strong therapeutic potential	284:311	strong therapeutic potential	284:311	Immunomodulatory glycolipids, among which α-galactosylceramide (KRN7000) is an iconic example, have shown strong therapeutic potential in a variety of conditions ranging from cancer and infection to autoimmune or neurodegenerative diseases.
31425910	5	86	theme	protein	1371:1377	arg1	kinase					1379:1384	the master p38 mitogen activated protein kinase	1338:1384	the master p38 mitogen activated protein kinase (p38 MAPK)	1338:1395	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
31425910	5	86	theme	protein	1371:1377	arg1	MAPK					1391:1394	p38 MAPK	1387:1394	p38 MAPK	1387:1394	The lipid tail has been then readily tailored by incorporating polyfluoroalkyl segments of varied lengths in view of favouring binding to the lipid binding site of the master p38 mitogen activated protein kinase (p38 MAPK), thereby polarizing the immune response in a cell-context dependent manner.
28253385	17	0	theme	disorder	2656:2663	arg1	genes					2665:2669	other glycosylation disorder genes	2636:2669	other glycosylation disorder genes	2636:2669	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	0	theme	disorder	2656:2663	arg1	SRD5A3					2625:2630	SRD5A3	2625:2630	SRD5A3	2625:2630	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	0	theme	disorder	2656:2663	arg1	cause					2697:2701	a cause	2695:2701	a cause of retinal dystrophy	2695:2722	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	6	1	theme	genetic	897:903	arg1	sequencing					952:961	targeted next-generation sequencing	927:961	targeted next-generation sequencing	927:961	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	6	1	theme	genetic	897:903	arg1	approaches					905:914	Molecular genetic approaches	887:914	Molecular genetic approaches	887:914	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	6	1	theme	genetic	897:903	arg1	mapping					977:983	autozygosity mapping	964:983	autozygosity mapping	964:983	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	6	1	theme	genetic	897:903	arg1	microarray					995:1004	apex microarray	990:1004	apex microarray	990:1004	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	4	2	with	Design	579:584	arg1	dystrophy					690:698	early-onset retinal dystrophy	670:698	early-onset retinal dystrophy as a primary manifestation	670:725	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	13	3	theme	Detailed	1885:1892	arg1	phenotyping					1901:1911	Detailed ocular phenotyping	1885:1911	Detailed ocular phenotyping	1885:1911	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	12	4	theme	p.	1791:1792	arg1	variant					1804:1810	p.(Trp19Ter) variant	1791:1810	p.(Trp19Ter) variant	1791:1810	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	4	theme	p.	1791:1792	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	10	5	theme	biochemical	1486:1496	arg1	results					1498:1504	genetic and biochemical results	1474:1504	clinical phenotypes as well as genetic and biochemical results	1443:1504	Main Outcomes and Measures Detailed clinical phenotypes as well as genetic and biochemical results.
28253385	17	6	theme	dystrophy	2714:2722	arg1	genes					2665:2669	other glycosylation disorder genes	2636:2669	other glycosylation disorder genes	2636:2669	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	6	theme	dystrophy	2714:2722	arg1	SRD5A3					2625:2630	SRD5A3	2625:2630	SRD5A3	2625:2630	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	6	theme	dystrophy	2714:2722	arg1	cause					2697:2701	a cause	2695:2701	a cause of retinal dystrophy	2695:2722	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	10	7	theme	genetic	1474:1480	arg1	results					1498:1504	genetic and biochemical results	1474:1504	clinical phenotypes as well as genetic and biochemical results	1443:1504	Main Outcomes and Measures Detailed clinical phenotypes as well as genetic and biochemical results.
28253385	12	8	theme	homozygous	1764:1773	arg1	variant					1804:1810	p.(Trp19Ter) variant	1791:1810	p.(Trp19Ter) variant	1791:1810	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	8	theme	homozygous	1764:1773	arg1	cause					1830:1834	the underlying cause	1815:1834	the underlying cause of early-onset retinal dystrophy in each family	1815:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	8	theme	homozygous	1764:1773	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	13	9	theme	mean	1965:1968	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	9	theme	mean	1965:1968	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	10	theme	refractive	2090:2099	arg1	error					2101:2105	myopia (mean [SD] refractive error	2072:2105	myopia (mean [SD] refractive error	2072:2105	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	1	11	theme	rare	210:213	arg1	type					148:151	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation	116:190	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	11	theme	rare	210:213	arg1	disorder					215:222	a rare disorder	208:222	a rare disorder of N-linked glycosylation	208:248	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	7	12	used	used	1135:1138	arg2	sequencing					1120:1129	whole-genome sequencing	1107:1129	whole-genome sequencing	1107:1129	Whole-exome sequencing or whole-genome sequencing was used to identify the causative variant.
28253385	7	12	used	used	1135:1138	arg2	sequencing					1093:1102	Whole-exome sequencing	1081:1102	Whole-exome sequencing	1081:1102	Whole-exome sequencing or whole-genome sequencing was used to identify the causative variant.
28253385	17	13	theme	other	2636:2640	arg1	genes					2665:2669	other glycosylation disorder genes	2636:2669	other glycosylation disorder genes	2636:2669	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	13	theme	other	2636:2640	arg1	SRD5A3					2625:2630	SRD5A3	2625:2630	SRD5A3	2625:2630	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	13	theme	other	2636:2640	arg1	cause					2697:2701	a cause	2695:2701	a cause of retinal dystrophy	2695:2722	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	4	14	theme	early-onset	670:680	arg1	dystrophy					690:698	early-onset retinal dystrophy	670:698	early-onset retinal dystrophy as a primary manifestation	670:725	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	7	15	theme	causative	1156:1164	arg1	variant					1166:1172	the causative variant	1152:1172	the causative variant	1152:1172	Whole-exome sequencing or whole-genome sequencing was used to identify the causative variant.
28253385	18	16	theme	progression	2906:2916	arg1	estimation					2868:2877	prognostic estimation	2857:2877	prognostic estimation of visual loss and disease progression	2857:2916	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	7	17	theme	whole-genome	1107:1118	arg1	sequencing					1120:1129	whole-genome sequencing	1107:1129	whole-genome sequencing	1107:1129	Whole-exome sequencing or whole-genome sequencing was used to identify the causative variant.
28253385	12	18	from	dystrophy	1859:1867	arg1	family					1877:1882	each family	1872:1882	each family	1872:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	15	19	from	abnormal	2287:2294	arg1	patients					2303:2310	all patients	2299:2310	all patients	2299:2310	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	15	20	theme	electrodiagnostic	2317:2333	arg1	testing					2335:2341	electrodiagnostic testing	2317:2341	electrodiagnostic testing	2317:2341	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	13	21	theme	mean	2080:2083	arg1	error					2101:2105	myopia (mean [SD] refractive error	2072:2105	myopia (mean [SD] refractive error	2072:2105	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	1	22	theme	5α-reductase	135:146	arg1	type					148:151	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation	116:190	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	22	theme	5α-reductase	135:146	arg1	disorder					215:222	a rare disorder	208:222	a rare disorder of N-linked glycosylation	208:248	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	22	theme	5α-reductase	135:146	arg1	SRD5A3-CDG					193:202	SRD5A3-CDG	193:202	SRD5A3-CDG	193:202	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	12	23	theme	whole-genome	1720:1731	arg1	sequencing					1733:1742	whole-genome sequencing	1720:1742	whole-genome sequencing	1720:1742	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	13	24	theme	[SD	1970:1972	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	24	theme	[SD	1970:1972	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	16	25	theme	early-onset	2468:2478	arg1	feature					2527:2533	a previously underdescribed feature	2499:2533	a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment	2499:2622	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	25	theme	early-onset	2468:2478	arg1	dystrophy					2488:2496	early-onset retinal dystrophy	2468:2496	early-onset retinal dystrophy	2468:2496	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	25	theme	early-onset	2468:2478	arg1	progressive					2570:2580	progressive	2570:2580	progressive	2570:2580	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	13	26	theme	aged	1937:1940	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	26	theme	aged	1937:1940	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	4	27	dep	individuals	627:637	arg1	families					656:663	4 unrelated families	644:663	4 unrelated families	644:663	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	4	28	with	Participants	599:610	arg1	dystrophy					690:698	early-onset retinal dystrophy	670:698	early-onset retinal dystrophy as a primary manifestation	670:725	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	15	29	dep	rod	2352:2354	arg1	dysfunction					2365:2375	dysfunction	2365:2375	dysfunction	2365:2375	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	13	30	theme	childhood-onset	2044:2058	arg1	nyctalopia					2060:2069	childhood-onset nyctalopia	2044:2069	childhood-onset nyctalopia	2044:2069	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	4	31	with	Setting	587:593	arg1	dystrophy					690:698	early-onset retinal dystrophy	670:698	early-onset retinal dystrophy as a primary manifestation	670:725	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	15	32	from	patients	2303:2310	arg1	abnormal					2287:2294	abnormal	2287:2294	abnormal	2287:2294	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	4	33	theme	comprehensive	737:749	arg1	assessment					762:771	comprehensive ophthalmic assessment	737:771	comprehensive ophthalmic assessment	737:771	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	16	34	theme	SRD5A3	2446:2451	arg1	gene					2453:2456	the SRD5A3 gene	2442:2456	the SRD5A3 gene	2442:2456	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	13	35	theme	[SD	2085:2087	arg1	error					2101:2105	myopia (mean [SD] refractive error	2072:2105	myopia (mean [SD] refractive error	2072:2105	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	1	36	theme	glycosylation	178:190	arg1	disorder					166:173	congenital disorder	155:173	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	16	37	theme	disorder	2553:2560	arg1	feature					2527:2533	a previously underdescribed feature	2499:2533	a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment	2499:2622	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	37	theme	disorder	2553:2560	arg1	dystrophy					2488:2496	early-onset retinal dystrophy	2468:2496	early-onset retinal dystrophy	2468:2496	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	37	theme	disorder	2553:2560	arg1	progressive					2570:2580	progressive	2570:2580	progressive	2570:2580	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	1	38	dep	type	148:151	arg1	disorder					166:173	congenital disorder	155:173	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	13	39	theme	early-onset	1924:1934	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	39	theme	early-onset	1924:1934	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	0	40	theme	Retinal	97:103	arg1	Dystrophy					105:113	Early-Onset Retinal Dystrophy	85:113	Early-Onset Retinal Dystrophy	85:113	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	3	41	theme	associated	558:567	arg1	features					569:576	other associated features	552:576	other associated features	552:576	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	3	42	theme	patients	445:452	arg1	series					435:440	a series	433:440	a series of patients with the same mutation in the SRD5A3 gene	433:494	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	15	43	theme	tomographic	2264:2274	arg1	scans					2276:2280	Fundus autofluorescence imaging and optical coherence tomographic scans	2210:2280	scans	2276:2280	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	18	44	theme	visual	2882:2887	arg1	loss					2889:2892	visual loss	2882:2892	visual loss	2882:2892	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	13	45	dep	[0.34	2011:2015	arg1	Snellen					2033:2039	Snellen	2033:2039	Snellen	2033:2039	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	3	46	dep	investigate	421:431	arg1	characterize					508:519	characterize	508:519	characterize its retinal manifestations and other associated features	508:576	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	13	47	theme	loss	1959:1962	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	47	theme	loss	1959:1962	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	2	48	theme	presenting	388:397	arg1	feature					399:405	a consistent primary presenting feature	367:405	a consistent primary presenting feature	367:405	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	2	48	theme	presenting	388:397	arg1	it					350:351	it	350:351	it	350:351	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	16	49	from	Mutations	2429:2437	arg1	gene					2453:2456	the SRD5A3 gene	2442:2456	the SRD5A3 gene	2442:2456	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	11	50	theme	mean	1584:1587	arg1	age					1594:1596	mean (SD) age	1584:1596	mean (SD) age at the most recent examination	1584:1627	Results The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity.
28253385	4	51	theme	electrodiagnostic	804:820	arg1	testing					822:828	electrodiagnostic testing	804:828	electrodiagnostic testing	804:828	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	0	52	theme	Steroid	15:21	arg1	Disorder					54:61	Steroid 5α-Reductase Type 3 Congenital Disorder	15:61	Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation	15:78	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	15	53	theme	autofluorescence	2217:2232	arg1	imaging					2234:2240	Fundus autofluorescence imaging and optical coherence tomographic scans	2210:2280	imaging	2234:2240	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	8	54	theme	Biochemical	1175:1185	arg1	profiling					1187:1195	Biochemical profiling	1175:1195	Biochemical profiling	1175:1195	Biochemical profiling was conducted to confirm a CDG type I defect.
28253385	6	55	theme	autozygosity	964:975	arg1	mapping					977:983	autozygosity mapping	964:983	autozygosity mapping	964:983	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	1	56	theme	Importance	116:125	arg1	type					148:151	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation	116:190	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	56	theme	Importance	116:125	arg1	disorder					215:222	a rare disorder	208:222	a rare disorder of N-linked glycosylation	208:248	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	56	theme	Importance	116:125	arg1	SRD5A3-CDG					193:202	SRD5A3-CDG	193:202	SRD5A3-CDG	193:202	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	14	57	theme	psychomotor	2191:2201	arg1	delay					2203:2207	psychomotor delay	2191:2207	psychomotor delay	2191:2207	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	0	58	theme	Type	36:39	arg1	Disorder					54:61	Steroid 5α-Reductase Type 3 Congenital Disorder	15:61	Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation	15:78	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	12	59	theme	underlying	1819:1828	arg1	cause					1830:1834	the underlying cause	1815:1834	the underlying cause of early-onset retinal dystrophy in each family	1815:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	59	theme	underlying	1819:1828	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	18	60	theme	eye	2803:2805	arg1	phenotypes					2807:2816	SRD5A3-associated eye phenotypes	2785:2816	SRD5A3-associated eye phenotypes	2785:2816	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	0	61	theme	Congenital	43:52	arg1	Disorder					54:61	Steroid 5α-Reductase Type 3 Congenital Disorder	15:61	Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation	15:78	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	12	62	theme	early-onset	1839:1849	arg1	dystrophy					1859:1867	early-onset retinal dystrophy	1839:1867	early-onset retinal dystrophy in each family	1839:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	6	63	theme	targeted	927:934	arg1	sequencing					952:961	targeted next-generation sequencing	927:961	targeted next-generation sequencing	927:961	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	13	64	theme	best-corrected	1975:1988	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	64	theme	best-corrected	1975:1988	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	12	65	from	cause	1830:1834	arg1	family					1877:1882	each family	1872:1882	each family	1872:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	2	66	theme	retinal	255:261	arg1	phenotype					263:271	Its retinal phenotype	251:271	Its retinal phenotype	251:271	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	0	67	with	Association	0:10	arg1	Dystrophy					105:113	Early-Onset Retinal Dystrophy	85:113	Early-Onset Retinal Dystrophy	85:113	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	1	68	theme	N-linked	227:234	arg1	glycosylation					236:248	N-linked glycosylation	227:248	N-linked glycosylation	227:248	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	12	69	theme	dystrophy	1859:1867	arg1	cause					1830:1834	the underlying cause	1815:1834	the underlying cause of early-onset retinal dystrophy in each family	1815:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	69	theme	dystrophy	1859:1867	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	16	70	theme	underdescribed	2512:2525	arg1	feature					2527:2533	a previously underdescribed feature	2499:2533	a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment	2499:2622	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	70	theme	underdescribed	2512:2525	arg1	dystrophy					2488:2496	early-onset retinal dystrophy	2468:2496	early-onset retinal dystrophy	2468:2496	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	70	theme	underdescribed	2512:2525	arg1	progressive					2570:2580	progressive	2570:2580	progressive	2570:2580	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	18	71	theme	phenotypes	2807:2816	arg1	delineation					2770:2780	Further delineation	2762:2780	Further delineation of SRD5A3-associated eye phenotypes	2762:2816	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	4	72	theme	affected	618:625	arg1	individuals					627:637	Seven affected individuals	612:637	Seven affected individuals	612:637	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	9	73	theme	phenotype	1251:1259	arg1	data					1261:1264	Patient phenotype data	1243:1264	Patient phenotype data	1243:1264	Patient phenotype data were collected over the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016.
28253385	2	74	theme	consistent	369:378	arg1	feature					399:405	a consistent primary presenting feature	367:405	a consistent primary presenting feature	367:405	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	2	74	theme	consistent	369:378	arg1	it					350:351	it	350:351	it	350:351	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	8	75	theme	type	1228:1231	arg1	defect					1235:1240	a CDG type I defect	1222:1240	a CDG type I defect	1222:1240	Biochemical profiling was conducted to confirm a CDG type I defect.
28253385	16	76	theme	Relevance	2419:2427	arg1	Mutations					2429:2437	Relevance Mutations	2419:2437	Relevance Mutations in the SRD5A3 gene	2419:2456	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	14	77	theme	learning	2165:2172	arg1	difficulties					2174:2185	learning difficulties	2165:2185	learning difficulties	2165:2185	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	4	78	from	individuals	627:637	arg1	Participants					599:610	Participants	599:610	Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation	599:725	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	4	78	from	individuals	627:637	arg1	Setting					587:593	Setting	587:593	Setting	587:593	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	4	78	from	individuals	627:637	arg1	Design					579:584	Design	579:584	Design	579:584	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	16	79	theme	retinal	2480:2486	arg1	feature					2527:2533	a previously underdescribed feature	2499:2533	a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment	2499:2622	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	79	theme	retinal	2480:2486	arg1	dystrophy					2488:2496	early-onset retinal dystrophy	2468:2496	early-onset retinal dystrophy	2468:2496	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	16	79	theme	retinal	2480:2486	arg1	progressive					2570:2580	progressive	2570:2580	progressive	2570:2580	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	14	80	theme	patients	2152:2159	arg1	patients					2152:2159	the 7 patients	2146:2159	the 7 patients	2146:2159	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	14	80	theme	patients	2152:2159	arg1	Six					2139:2141	Six	2139:2141	Six	2139:2141	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	13	81	theme	visual	1952:1957	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	81	theme	visual	1952:1957	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	6	82	theme	Molecular	887:895	arg1	sequencing					952:961	targeted next-generation sequencing	927:961	targeted next-generation sequencing	927:961	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	6	82	theme	Molecular	887:895	arg1	approaches					905:914	Molecular genetic approaches	887:914	Molecular genetic approaches	887:914	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	6	82	theme	Molecular	887:895	arg1	mapping					977:983	autozygosity mapping	964:983	autozygosity mapping	964:983	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	6	82	theme	Molecular	887:895	arg1	microarray					995:1004	apex microarray	990:1004	apex microarray	990:1004	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	3	83	theme	other	552:556	arg1	features					569:576	other associated features	552:576	other associated features	552:576	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	15	84	theme	coherence	2254:2262	arg1	scans					2276:2280	Fundus autofluorescence imaging and optical coherence tomographic scans	2210:2280	scans	2276:2280	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	18	85	theme	Further	2762:2768	arg1	delineation					2770:2780	Further delineation	2762:2780	Further delineation of SRD5A3-associated eye phenotypes	2762:2816	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	6	86	theme	apex	990:993	arg1	microarray					995:1004	apex microarray	990:1004	apex microarray	990:1004	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	14	87	contain	had	2161:2163	arg1	patients					2152:2159	the 7 patients	2146:2159	the 7 patients	2146:2159	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	14	87	contain	had	2161:2163	arg2	difficulties					2174:2185	learning difficulties	2165:2185	learning difficulties	2165:2185	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	14	87	contain	had	2161:2163	arg2	delay					2203:2207	psychomotor delay	2191:2207	psychomotor delay	2191:2207	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	14	87	contain	had	2161:2163	arg1	Six					2139:2141	Six	2139:2141	Six	2139:2141	Six of the 7 patients had learning difficulties and psychomotor delay.
28253385	10	88	theme	clinical	1443:1450	arg1	phenotypes					1452:1461	clinical phenotypes	1443:1461	clinical phenotypes as well as genetic and biochemical results	1443:1504	Main Outcomes and Measures Detailed clinical phenotypes as well as genetic and biochemical results.
28253385	17	89	theme	retinal	2706:2712	arg1	dystrophy					2714:2722	retinal dystrophy	2706:2722	retinal dystrophy	2706:2722	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	12	90	theme	same	1759:1762	arg1	variant					1804:1810	p.(Trp19Ter) variant	1791:1810	p.(Trp19Ter) variant	1791:1810	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	90	theme	same	1759:1762	arg1	cause					1830:1834	the underlying cause	1815:1834	the underlying cause of early-onset retinal dystrophy in each family	1815:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	90	theme	same	1759:1762	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	4	91	theme	retinal	682:688	arg1	dystrophy					690:698	early-onset retinal dystrophy	670:698	early-onset retinal dystrophy as a primary manifestation	670:725	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	9	92	theme	ophthalmic	1300:1309	arg1	follow-up					1311:1319	ophthalmic follow-up	1300:1319	ophthalmic follow-up	1300:1319	Patient phenotype data were collected over the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016.
28253385	2	93	theme	disease	322:328	arg1	recognition					330:340	disease recognition	322:340	disease recognition	322:340	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	12	94	theme	SRD5A3	1775:1780	arg1	variant					1804:1810	p.(Trp19Ter) variant	1791:1810	p.(Trp19Ter) variant	1791:1810	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	94	theme	SRD5A3	1775:1780	arg1	cause					1830:1834	the underlying cause	1815:1834	the underlying cause of early-onset retinal dystrophy in each family	1815:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	94	theme	SRD5A3	1775:1780	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	1	95	link	N-linked	227:234	arg1	glycosylation					236:248	N-linked glycosylation	227:248	N-linked glycosylation	227:248	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	16	96	from	Conclusions	2403:2413	arg1	gene					2453:2456	the SRD5A3 gene	2442:2456	the SRD5A3 gene	2442:2456	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	12	97	from	family	1877:1882	arg1	cause					1830:1834	the underlying cause	1815:1834	the underlying cause of early-onset retinal dystrophy in each family	1815:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	97	from	family	1877:1882	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	18	98	theme	SRD5A3-associated	2785:2801	arg1	phenotypes					2807:2816	SRD5A3-associated eye phenotypes	2785:2816	SRD5A3-associated eye phenotypes	2785:2816	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	4	99	theme	unrelated	646:654	arg1	families					656:663	4 unrelated families	644:663	4 unrelated families	644:663	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	11	100	from	examination	1617:1627	arg1	age					1594:1596	mean (SD) age	1584:1596	mean (SD) age at the most recent examination	1584:1627	Results The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity.
28253385	16	101	theme	visual	2606:2611	arg1	impairment					2613:2622	serious visual impairment	2598:2622	serious visual impairment	2598:2622	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	17	102	theme	glycosylation	2642:2654	arg1	genes					2665:2669	other glycosylation disorder genes	2636:2669	other glycosylation disorder genes	2636:2669	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	102	theme	glycosylation	2642:2654	arg1	SRD5A3					2625:2630	SRD5A3	2625:2630	SRD5A3	2625:2630	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	17	102	theme	glycosylation	2642:2654	arg1	cause					2697:2701	a cause	2695:2701	a cause of retinal dystrophy	2695:2722	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	18	103	theme	disease	2898:2904	arg1	progression					2906:2916	disease progression	2898:2916	disease progression	2898:2916	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	1	104	theme	Steroid	127:133	arg1	type					148:151	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation	116:190	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	104	theme	Steroid	127:133	arg1	disorder					215:222	a rare disorder	208:222	a rare disorder of N-linked glycosylation	208:248	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	104	theme	Steroid	127:133	arg1	SRD5A3-CDG					193:202	SRD5A3-CDG	193:202	SRD5A3-CDG	193:202	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	11	105	dep	Results	1507:1513	arg1	consisted					1526:1534	consisted	1526:1534	consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity	1526:1690	Results The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity.
28253385	4	106	theme	ophthalmic	751:760	arg1	assessment					762:771	comprehensive ophthalmic assessment	737:771	comprehensive ophthalmic assessment	737:771	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	3	107	with	patients	445:452	arg1	mutation					468:475	the same mutation	459:475	the same mutation in the SRD5A3 gene	459:494	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	9	108	theme	years	1346:1350	arg1	period					1333:1338	a period	1331:1338	a period of 20 years	1331:1350	Patient phenotype data were collected over the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016.
28253385	11	109	theme	recent	1610:1615	arg1	examination					1617:1627	the most recent examination	1601:1627	the most recent examination	1601:1627	Results The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity.
28253385	13	110	theme	≤3	1942:1943	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	110	theme	≤3	1942:1943	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	0	111	theme	Glycosylation	66:78	arg1	Disorder					54:61	Steroid 5α-Reductase Type 3 Congenital Disorder	15:61	Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation	15:78	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	7	112	theme	Whole-exome	1081:1091	arg1	sequencing					1093:1102	Whole-exome sequencing	1081:1102	Whole-exome sequencing	1081:1102	Whole-exome sequencing or whole-genome sequencing was used to identify the causative variant.
28253385	1	113	theme	congenital	155:164	arg1	disorder					166:173	congenital disorder	155:173	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	16	114	theme	SRD5A3-CDG	2542:2551	arg1	disorder					2553:2560	the SRD5A3-CDG disorder	2538:2560	the SRD5A3-CDG disorder	2538:2560	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
28253385	4	115	theme	primary	705:711	arg1	manifestation					713:725	a primary manifestation	703:725	a primary manifestation	703:725	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	13	116	theme	ocular	1894:1899	arg1	phenotyping					1901:1911	Detailed ocular phenotyping	1885:1911	Detailed ocular phenotyping	1885:1911	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	0	117	theme	Early-Onset	85:95	arg1	Dystrophy					105:113	Early-Onset Retinal Dystrophy	85:113	Early-Onset Retinal Dystrophy	85:113	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	18	118	theme	prognostic	2857:2866	arg1	estimation					2868:2877	prognostic estimation	2857:2877	prognostic estimation of visual loss and disease progression	2857:2916	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	5	119	theme	Developmental	831:843	arg1	findings					858:865	Developmental and systemic findings	831:865	Developmental and systemic findings	831:865	Developmental and systemic findings were also recorded.
28253385	11	120	dep	participants	1541:1552	arg1	females					1557:1563	5 females	1555:1563	5 females	1555:1563	Results The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity.
28253385	11	120	dep	participants	1541:1552	arg1	males					1571:1575	2 males	1569:1575	2 males	1569:1575	Results The cohort consisted of 7 participants (5 females and 2 males) whose mean (SD) age at the most recent examination was 17.1 (3.9) years and who were all of South Asian ethnicity.
28253385	13	121	theme	myopia	2072:2077	arg1	error					2101:2105	myopia (mean [SD] refractive error	2072:2105	myopia (mean [SD] refractive error	2072:2105	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	12	122	theme	Whole-exome	1693:1703	arg1	sequencing					1705:1714	Whole-exome sequencing	1693:1714	Whole-exome sequencing	1693:1714	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	13	123	theme	visual	1990:1995	arg1	acuity					1997:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity	1924:2002	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	13	123	theme	visual	1990:1995	arg1	years					1945:1949	aged ≤3 years	1937:1949	aged ≤3 years	1937:1949	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	18	124	theme	loss	2889:2892	arg1	estimation					2868:2877	prognostic estimation	2857:2877	prognostic estimation of visual loss and disease progression	2857:2916	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	13	125	dep	-6.71	2108:2112	arg1	[-4.22					2114:2119	[-4.22	2114:2119	[-4.22	2114:2119	Detailed ocular phenotyping identified early-onset (aged ≤3 years) visual loss (mean [SD] best-corrected visual acuity, +0.95 [0.34] logMAR [20/180 Snellen]), childhood-onset nyctalopia, myopia (mean [SD] refractive error, -6.71 [-4.22]), and nystagmus.
28253385	18	126	theme	genetic	2834:2840	arg1	counseling					2842:2851	genetic counseling	2834:2851	genetic counseling for prognostic estimation of visual loss and disease progression	2834:2916	Further delineation of SRD5A3-associated eye phenotypes can help inform genetic counseling for prognostic estimation of visual loss and disease progression.
28253385	17	127	theme	systemic	2734:2741	arg1	features					2743:2750	systemic features	2734:2750	systemic features	2734:2750	SRD5A3 and other glycosylation disorder genes should be considered as a cause of retinal dystrophy even when systemic features are mild.
28253385	4	128	theme	retinal	784:790	arg1	imaging					792:798	retinal imaging	784:798	retinal imaging	784:798	Design, Setting and Participants Seven affected individuals from 4 unrelated families with early-onset retinal dystrophy as a primary manifestation underwent comprehensive ophthalmic assessment, including retinal imaging and electrodiagnostic testing.
28253385	2	129	theme	primary	380:386	arg1	feature					399:405	a consistent primary presenting feature	367:405	a consistent primary presenting feature	367:405	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	2	129	theme	primary	380:386	arg1	it					350:351	it	350:351	it	350:351	Its retinal phenotype is not well described but could be important for disease recognition because it appears to be a consistent primary presenting feature.
28253385	0	130	theme	5α-Reductase	23:34	arg1	Disorder					54:61	Steroid 5α-Reductase Type 3 Congenital Disorder	15:61	Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation	15:78	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	15	131	theme	optical	2246:2252	arg1	scans					2276:2280	Fundus autofluorescence imaging and optical coherence tomographic scans	2210:2280	scans	2276:2280	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	9	132	theme	follow-up	1311:1319	arg1	course					1290:1295	the course	1286:1295	the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016	1286:1404	Patient phenotype data were collected over the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016.
28253385	5	133	theme	systemic	849:856	arg1	findings					858:865	Developmental and systemic findings	831:865	Developmental and systemic findings	831:865	Developmental and systemic findings were also recorded.
28253385	10	134	theme	Main	1407:1410	arg1	Outcomes					1412:1419	Main Outcomes	1407:1419	Main Outcomes	1407:1419	Main Outcomes and Measures Detailed clinical phenotypes as well as genetic and biochemical results.
28253385	3	135	theme	same	463:466	arg1	mutation					468:475	the same mutation	459:475	the same mutation in the SRD5A3 gene	459:494	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	0	136	theme	Disorder	54:61	arg1	Association					0:10	Association	0:10	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.	0:114	Association of Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation With Early-Onset Retinal Dystrophy.
28253385	15	137	theme	Fundus	2210:2215	arg1	imaging					2234:2240	Fundus autofluorescence imaging and optical coherence tomographic scans	2210:2280	imaging	2234:2240	Fundus autofluorescence imaging and optical coherence tomographic scans were abnormal in all patients, and electrodiagnostic testing revealed rod and cone dysfunction in the 5 patients tested.
28253385	12	138	theme	retinal	1851:1857	arg1	dystrophy					1859:1867	early-onset retinal dystrophy	1839:1867	early-onset retinal dystrophy in each family	1839:1882	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	6	139	theme	next-generation	936:950	arg1	sequencing					952:961	targeted next-generation sequencing	927:961	targeted next-generation sequencing	927:961	Molecular genetic approaches, including targeted next-generation sequencing, autozygosity mapping, and apex microarray, were tried to reach a diagnosis; all participants were mutation negative.
28253385	3	140	from	mutation	468:475	arg1	gene					491:494	the SRD5A3 gene	480:494	the SRD5A3 gene	480:494	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	8	141	theme	CDG	1224:1226	arg1	defect					1235:1240	a CDG type I defect	1222:1240	a CDG type I defect	1222:1240	Biochemical profiling was conducted to confirm a CDG type I defect.
28253385	9	142	theme	Patient	1243:1249	arg1	data					1261:1264	Patient phenotype data	1243:1264	Patient phenotype data	1243:1264	Patient phenotype data were collected over the course of ophthalmic follow-up, spanning a period of 20 years, beginning March 20, 1997, through September 15, 2016.
28253385	3	143	theme	SRD5A3	484:489	arg1	gene					491:494	the SRD5A3 gene	480:494	the SRD5A3 gene	480:494	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	1	144	theme	glycosylation	236:248	arg1	type					148:151	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation	116:190	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG)	116:203	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	1	144	theme	glycosylation	236:248	arg1	disorder					215:222	a rare disorder	208:222	a rare disorder of N-linked glycosylation	208:248	Importance Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare disorder of N-linked glycosylation.
28253385	8	145	theme	I	1233:1233	arg1	defect					1235:1240	a CDG type I defect	1222:1240	a CDG type I defect	1222:1240	Biochemical profiling was conducted to confirm a CDG type I defect.
28253385	12	146	theme	Trp19Ter	1794:1801	arg1	variant					1804:1810	p.(Trp19Ter) variant	1791:1810	p.(Trp19Ter) variant	1791:1810	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	12	146	theme	Trp19Ter	1794:1801	arg1	c.57G>A					1782:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	the same homozygous SRD5A3 c.57G>A	1755:1788	Whole-exome sequencing and whole-genome sequencing identified the same homozygous SRD5A3 c.57G>A, p.(Trp19Ter) variant as the underlying cause of early-onset retinal dystrophy in each family.
28253385	3	147	theme	retinal	525:531	arg1	manifestations					533:546	its retinal manifestations	521:546	its retinal manifestations	521:546	Objective To investigate a series of patients with the same mutation in the SRD5A3 gene and thereby characterize its retinal manifestations and other associated features.
28253385	16	148	theme	serious	2598:2604	arg1	impairment					2613:2622	serious visual impairment	2598:2622	serious visual impairment	2598:2622	Conclusions and Relevance Mutations in the SRD5A3 gene may cause early-onset retinal dystrophy, a previously underdescribed feature of the SRD5A3-CDG disorder that is progressive and may lead to serious visual impairment.
30933973	10	0	theme	HIV-infected	1991:2002	arg1	persons					2004:2010	HIV-infected persons	1991:2010	HIV-infected persons	1991:2010	This modeling framework may also inform the study of VRC01 in the treatment of HIV-infected persons.
30933973	7	1	theme	given	1341:1345	arg1	pseudovirus					1351:1361	a given Env pseudovirus	1339:1361	a given Env pseudovirus	1339:1361	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	9	2	theme	cysteines	1783:1791	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	length					1699:1704	the length	1695:1704	the length of gp120	1695:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	number					1739:1744	the number	1735:1744	the number of cysteines in gp120	1735:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	number					1773:1778	the number	1769:1778	the number of cysteines in Env	1769:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	length					1720:1725	the length	1716:1725	the length of Env	1716:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	2	theme	cysteines	1783:1791	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	8	3	theme	0.355	1546:1550	arg1	R2					1540:1541	an average validated R2	1519:1541	an average validated R2 of 0.355	1519:1550	Quantitative log IC50 was predicted with an average validated R2 of 0.355.
30933973	10	4	from	study	1956:1960	arg1	treatment					1978:1986	the treatment	1974:1986	the treatment of HIV-infected persons	1974:2010	This modeling framework may also inform the study of VRC01 in the treatment of HIV-infected persons.
30933973	6	5	theme	learning	1164:1171	arg1	method					1173:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	6	5	theme	learning	1164:1171	arg1	Learner					1108:1114	Super Learner	1102:1114	Super Learner	1102:1114	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	2	6	theme	secondary	243:251	arg1	objective					253:261	A secondary objective	241:261	A secondary objective of AMP	241:268	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	9	7	from	length	1720:1725	arg1	gp120					1762:1766	gp120	1762:1766	gp120	1762:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	7	from	length	1720:1725	arg1	Env					1796:1798	Env	1796:1798	Env	1796:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	length					1699:1704	the length	1695:1704	the length of gp120	1695:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	number					1739:1744	the number	1735:1744	the number of cysteines in gp120	1735:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	number					1773:1778	the number	1769:1778	the number of cysteines in Env	1769:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	length					1720:1725	the length	1716:1725	the length of Env	1716:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	8	from	gp120	1762:1766	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	6	9	theme	ensemble-based	1133:1146	arg1	method					1173:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	6	9	theme	ensemble-based	1133:1146	arg1	Learner					1108:1114	Super Learner	1102:1114	Super Learner	1102:1114	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	1	10	theme	HIV-1	175:179	arg1	infection					181:189	HIV-1 infection	175:189	HIV-1 infection	175:189	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30933973	4	11	with	importance	872:881	arg1	methods					918:924	classification and regression methods	888:924	methods	918:924	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	7	12	theme	neutralization	1305:1318	arg1	right-censored					1366:1379	right-censored	1366:1379	right-censored	1366:1379	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	12	theme	neutralization	1305:1318	arg1	resistance					1393:1402	resistance	1393:1402	resistance	1393:1402	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	12	theme	neutralization	1305:1318	arg1	titer					1320:1324	the IC50 neutralization titer	1296:1324	the IC50 neutralization titer of VRC01 for a given Env pseudovirus	1296:1361	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	9	13	theme	potential	1807:1815	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	13	theme	potential	1807:1815	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	13	theme	potential	1807:1815	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	13	theme	potential	1807:1815	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	13	theme	potential	1807:1815	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	13	theme	potential	1807:1815	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	4	14	theme	primary	573:579	arg1	analysis					587:594	an adequately powered primary sieve analysis	551:594	an adequately powered primary sieve analysis for AMP	551:602	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	6	15	theme	nonparametric	1119:1131	arg1	method					1173:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	6	15	theme	nonparametric	1119:1131	arg1	Learner					1108:1114	Super Learner	1102:1114	Super Learner	1102:1114	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	9	16	theme	glycosylation	1826:1838	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	16	theme	glycosylation	1826:1838	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	16	theme	glycosylation	1826:1838	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	16	theme	glycosylation	1826:1838	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	16	theme	glycosylation	1826:1838	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	16	theme	glycosylation	1826:1838	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	length					1699:1704	the length	1695:1704	the length of gp120	1695:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	number					1739:1744	the number	1735:1744	the number of cysteines in gp120	1735:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	number					1773:1778	the number	1769:1778	the number of cysteines in Env	1769:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	length					1720:1725	the length	1716:1725	the length of Env	1716:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	17	theme	gp120	1709:1713	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	1	18	theme	Antibody	198:205	arg1	trials					233:238	the Antibody Mediated Prevention (AMP) trials	194:238	the Antibody Mediated Prevention (AMP) trials	194:238	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30933973	6	19	theme	primary	1204:1210	arg1	analysis					1218:1225	the primary sieve analysis	1200:1225	the primary sieve analysis	1200:1225	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	6	20	theme	sieve	1212:1216	arg1	analysis					1218:1225	the primary sieve analysis	1200:1225	the primary sieve analysis	1200:1225	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	3	21	theme	statistical	522:532	arg1	power					534:538	low statistical power	518:538	low statistical power	518:538	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	6	22	theme	Super	1102:1106	arg1	method					1173:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	6	22	theme	Super	1102:1106	arg1	Learner					1108:1114	Super Learner	1102:1114	Super Learner	1102:1114	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	7	23	theme	resistance	1266:1275	arg1	outcome					1277:1283	the dichotomous resistance outcome	1250:1283	the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets	1250:1475	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	9	24	theme	top	1851:1853	arg1	features					1855:1862	the top features	1847:1862	the top features	1847:1862	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	24	theme	top	1851:1853	arg1	advanced					1872:1879	advanced	1872:1879	advanced	1872:1879	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	4	25	theme	Env	654:656	arg1	features					670:677	Env AA sequence features	654:677	Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database	654:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	4	26	from	database	728:735	arg1	features					670:677	Env AA sequence features	654:677	Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database	654:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	4	26	from	database	728:735	arg1	pseudoviruses					698:710	611 HIV-1 gp160 pseudoviruses	682:710	611 HIV-1 gp160 pseudoviruses from the CATNAP database	682:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	9	27	from	cysteines	1749:1757	arg1	gp120					1762:1766	gp120	1762:1766	gp120	1762:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	28	theme	binding	1675:1681	arg1	footprints					1683:1692	the VRC01 and CD4 binding footprints	1657:1692	footprints	1683:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	0	29	theme	sequence	62:69	arg1	features					71:78	HIV-1 gp160 sequence features	50:78	HIV-1 gp160 sequence features	50:78	Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.
30933973	9	30	theme	Env	1730:1732	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	length					1699:1704	the length	1695:1704	the length of gp120	1695:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	number					1739:1744	the number	1735:1744	the number of cysteines in gp120	1735:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	number					1773:1778	the number	1769:1778	the number of cysteines in Env	1769:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	length					1720:1725	the length	1716:1725	the length of Env	1716:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	30	theme	Env	1730:1732	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	4	31	theme	predictive	861:870	arg1	importance					872:881	their predictive importance	855:881	their predictive importance with classification and regression methods	855:924	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	9	32	theme	CD4	1671:1673	arg1	footprints					1683:1692	the VRC01 and CD4 binding footprints	1657:1692	footprints	1683:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	10	33	theme	modeling	1917:1924	arg1	framework					1926:1934	This modeling framework	1912:1934	This modeling framework	1912:1934	This modeling framework may also inform the study of VRC01 in the treatment of HIV-infected persons.
30933973	4	34	dep	predict	787:793	arg1	models					770:775	models	770:775	models that best predict the neutralization readouts; and (2)	770:830	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	4	35	theme	HIV-1	686:690	arg1	pseudoviruses					698:710	611 HIV-1 gp160 pseudoviruses	682:710	611 HIV-1 gp160 pseudoviruses from the CATNAP database	682:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	5	36	theme	learning	970:977	arg1	algorithms					979:988	machine learning algorithms	962:988	machine learning algorithms	962:988	The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation.
30933973	9	37	from	cysteines	1783:1791	arg1	Env					1796:1798	Env	1796:1798	Env	1796:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	7	38	theme	hold-out	1459:1466	arg1	datasets					1468:1475	the two hold-out datasets	1451:1475	the two hold-out datasets	1451:1475	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	4	39	theme	AA	840:841	arg1	features					843:850	rank AA features	835:850	rank AA features	835:850	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	9	40	theme	sieve	1896:1900	arg1	analysis					1902:1909	the primary sieve analysis	1884:1909	the primary sieve analysis	1884:1909	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	4	41	theme	pseudoviruses	698:710	arg1	features					670:677	Env AA sequence features	654:677	Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database	654:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	2	42	theme	envelope	362:369	arg1	AA					389:390	AA	389:390	AA	389:390	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	2	42	theme	envelope	362:369	arg1	acid					383:386	HIV-1 envelope (Env) amino acid	356:386	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	4	43	theme	sequence	661:668	arg1	features					670:677	Env AA sequence features	654:677	Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database	654:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	7	44	theme	validated	1421:1429	arg1	AUC					1431:1433	an average validated AUC	1410:1433	an average validated AUC of 0.868 across the two hold-out datasets	1410:1475	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	5	45	theme	cross-validation	1048:1063	arg1	validation					1078:1087	cross-validation and hold-out validation	1048:1087	cross-validation and hold-out validation	1048:1087	The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation.
30933973	1	46	theme	neutralizing	93:104	arg1	VRC01					122:126	The broadly neutralizing antibody (bnAb) VRC01	81:126	The broadly neutralizing antibody (bnAb) VRC01	81:126	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30933973	2	47	theme	amino	377:381	arg1	AA					389:390	AA	389:390	AA	389:390	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	2	47	theme	amino	377:381	arg1	acid					383:386	HIV-1 envelope (Env) amino acid	356:386	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	0	48	theme	VRC01	14:18	arg1	sensitivity					35:45	VRC01 neutralization sensitivity	14:45	VRC01 neutralization sensitivity	14:45	Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.
30933973	5	49	theme	hold-out	1069:1076	arg1	validation					1078:1087	cross-validation and hold-out validation	1048:1087	cross-validation and hold-out validation	1048:1087	The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation.
30933973	2	50	theme	Env	372:374	arg1	AA					389:390	AA	389:390	AA	389:390	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	2	50	theme	Env	372:374	arg1	acid					383:386	HIV-1 envelope (Env) amino acid	356:386	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	0	51	theme	sensitivity	35:45	arg1	Prediction					0:9	Prediction	0:9	Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.	0:79	Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.
30933973	9	52	from	length	1699:1704	arg1	gp120					1762:1766	gp120	1762:1766	gp120	1762:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	52	from	length	1699:1704	arg1	Env					1796:1798	Env	1796:1798	Env	1796:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	8	53	theme	Quantitative	1478:1489	arg1	IC50					1495:1498	Quantitative log IC50	1478:1498	Quantitative log IC50	1478:1498	Quantitative log IC50 was predicted with an average validated R2 of 0.355.
30933973	2	54	theme	prevention	319:328	arg1	PE					340:341	PE	340:341	PE	340:341	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	2	54	theme	prevention	319:328	arg1	efficacy					330:337	VRC01 prevention efficacy	313:337	VRC01 prevention efficacy (PE)	313:342	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	4	55	dep	develop	762:768	arg1	1					756:756	1	756:756	1	756:756	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	7	56	dep	right-censored	1366:1379	arg1	right-censored					1366:1379	right-censored	1366:1379	right-censored	1366:1379	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	56	dep	right-censored	1366:1379	arg1	resistance					1393:1402	resistance	1393:1402	resistance	1393:1402	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	56	dep	right-censored	1366:1379	arg1	titer					1320:1324	the IC50 neutralization titer	1296:1324	the IC50 neutralization titer of VRC01 for a given Env pseudovirus	1296:1361	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	2	57	theme	sequence	393:400	arg1	features					402:409	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	9	58	theme	cysteines	1749:1757	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	length					1699:1704	the length	1695:1704	the length of gp120	1695:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	number					1739:1744	the number	1735:1744	the number of cysteines in gp120	1735:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	number					1773:1778	the number	1769:1778	the number of cysteines in Env	1769:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	length					1720:1725	the length	1716:1725	the length of Env	1716:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	58	theme	cysteines	1749:1757	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	length					1699:1704	the length	1695:1704	the length of gp120	1695:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	number					1739:1744	the number	1735:1744	the number of cysteines in gp120	1735:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	number					1773:1778	the number	1769:1778	the number of cysteines in Env	1769:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	length					1720:1725	the length	1716:1725	the length of Env	1716:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	59	from	Env	1796:1798	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	3	60	theme	exhaustive	415:424	arg1	analysis					426:433	An exhaustive analysis	412:433	An exhaustive analysis	412:433	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	1	61	theme	Mediated	207:214	arg1	trials					233:238	the Antibody Mediated Prevention (AMP) trials	194:238	the Antibody Mediated Prevention (AMP) trials	194:238	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30933973	3	62	theme	AA	470:471	arg1	feature					473:479	every AA feature	464:479	every AA feature with sufficient variation	464:505	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	0	63	theme	gp160	56:60	arg1	features					71:78	HIV-1 gp160 sequence features	50:78	HIV-1 gp160 sequence features	50:78	Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.
30933973	9	64	link	N-linked	1817:1824	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	64	link	N-linked	1817:1824	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	64	link	N-linked	1817:1824	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	64	link	N-linked	1817:1824	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	64	link	N-linked	1817:1824	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	64	link	N-linked	1817:1824	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	10	65	theme	VRC01	1965:1969	arg1	study					1956:1960	the study	1952:1960	the study of VRC01 in the treatment of HIV-infected persons	1952:2010	This modeling framework may also inform the study of VRC01 in the treatment of HIV-infected persons.
30933973	8	66	theme	validated	1530:1538	arg1	R2					1540:1541	an average validated R2	1519:1541	an average validated R2 of 0.355	1519:1550	Quantitative log IC50 was predicted with an average validated R2 of 0.355.
30933973	2	67	theme	AMP	266:268	arg1	objective					253:261	A secondary objective	241:261	A secondary objective of AMP	241:268	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	9	68	theme	neutralization	1573:1586	arg1	sensitivity					1588:1598	neutralization sensitivity	1573:1598	neutralization sensitivity	1573:1598	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	7	69	theme	Env	1347:1349	arg1	pseudovirus					1351:1361	a given Env pseudovirus	1339:1361	a given Env pseudovirus	1339:1361	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	0	70	theme	HIV-1	50:54	arg1	gp160					56:60	HIV-1 gp160	50:60	HIV-1 gp160 sequence features	50:78	Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.
30933973	9	71	from	number	1773:1778	arg1	gp120					1762:1766	gp120	1762:1766	gp120	1762:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	71	from	number	1773:1778	arg1	Env					1796:1798	Env	1796:1798	Env	1796:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	6	72	theme	cross-validated	1148:1162	arg1	method					1173:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	a nonparametric ensemble-based cross-validated learning method	1117:1178	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	6	72	theme	cross-validated	1148:1162	arg1	Learner					1108:1114	Super Learner	1102:1114	Super Learner	1102:1114	We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis.
30933973	7	73	theme	VRC01	1329:1333	arg1	right-censored					1366:1379	right-censored	1366:1379	right-censored	1366:1379	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	73	theme	VRC01	1329:1333	arg1	resistance					1393:1402	resistance	1393:1402	resistance	1393:1402	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	73	theme	VRC01	1329:1333	arg1	titer					1320:1324	the IC50 neutralization titer	1296:1324	the IC50 neutralization titer of VRC01 for a given Env pseudovirus	1296:1361	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	3	74	theme	sufficient	486:495	arg1	variation					497:505	sufficient variation	486:505	sufficient variation	486:505	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	length					1699:1704	the length	1695:1704	the length of gp120	1695:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	number					1739:1744	the number	1735:1744	the number of cysteines in gp120	1735:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	number					1773:1778	the number	1769:1778	the number of cysteines in Env	1769:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	length					1720:1725	the length	1716:1725	the length of Env	1716:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	75	theme	surface-accessible	1626:1643	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	76	theme	N-linked	1817:1824	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	76	theme	N-linked	1817:1824	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	76	theme	N-linked	1817:1824	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	76	theme	N-linked	1817:1824	arg1	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	76	theme	N-linked	1817:1824	arg1	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	76	theme	N-linked	1817:1824	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	4	77	theme	powered	565:571	arg1	analysis					587:594	an adequately powered primary sieve analysis	551:594	an adequately powered primary sieve analysis for AMP	551:602	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	7	78	theme	IC50	1300:1303	arg1	right-censored					1366:1379	right-censored	1366:1379	right-censored	1366:1379	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	78	theme	IC50	1300:1303	arg1	resistance					1393:1402	resistance	1393:1402	resistance	1393:1402	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	7	78	theme	IC50	1300:1303	arg1	titer					1320:1324	the IC50 neutralization titer	1296:1324	the IC50 neutralization titer of VRC01 for a given Env pseudovirus	1296:1361	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	4	79	theme	sieve	581:585	arg1	analysis					587:594	an adequately powered primary sieve analysis	551:594	an adequately powered primary sieve analysis for AMP	551:602	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	5	80	theme	machine	962:968	arg1	learning					970:977	machine learning	962:977	machine learning algorithms	962:988	The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation.
30933973	3	81	theme	low	518:520	arg1	power					534:538	low statistical power	518:538	low statistical power	518:538	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	1	82	theme	bnAb	116:119	arg1	VRC01					122:126	The broadly neutralizing antibody (bnAb) VRC01	81:126	The broadly neutralizing antibody (bnAb) VRC01	81:126	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30933973	9	83	gly	glycosylation	1826:1838	arg2	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg1	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg1	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	residues					1645:1652	26 surface-accessible residues	1623:1652	26 surface-accessible residues in the VRC01 and CD4 binding footprints	1623:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	sites					1840:1844	4 potential N-linked glycosylation sites	1805:1844	4 potential N-linked glycosylation sites	1805:1844	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg1	gp120					1709:1713	gp120	1709:1713	gp120	1709:1713	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	4					1805:1805	4	1805:1805	4	1805:1805	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	Env					1730:1732	Env	1730:1732	Env	1730:1732	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	cysteines					1749:1757	cysteines	1749:1757	cysteines in gp120	1749:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	gp120					1762:1766	gp120	1762:1766	gp120	1762:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg2	Env					1796:1798	Env	1796:1798	Env	1796:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	83	gly	glycosylation	1826:1838	arg1	cysteines					1783:1791	cysteines	1783:1791	cysteines in Env	1783:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	2	84	theme	sieve	279:283	arg1	analysis					285:292	sieve analysis	279:292	sieve analysis	279:292	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	4	85	theme	neutralization	799:812	arg1	readouts					814:821	the neutralization readouts	795:821	the neutralization readouts	795:821	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	5	86	from	split	943:947	arg1	half					952:955	half	952:955	half	952:955	The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation.
30933973	7	87	theme	dichotomous	1254:1264	arg1	outcome					1277:1283	the dichotomous resistance outcome	1250:1283	the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets	1250:1475	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	9	88	from	residues	1645:1652	arg1	VRC01					1661:1665	the VRC01 and CD4 binding footprints	1657:1692	VRC01	1661:1665	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	88	from	residues	1645:1652	arg1	footprints					1683:1692	the VRC01 and CD4 binding footprints	1657:1692	footprints	1683:1692	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	89	theme	primary	1888:1894	arg1	analysis					1902:1909	the primary sieve analysis	1884:1909	the primary sieve analysis	1884:1909	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	10	90	theme	persons	2004:2010	arg1	treatment					1978:1986	the treatment	1974:1986	the treatment of HIV-infected persons	1974:2010	This modeling framework may also inform the study of VRC01 in the treatment of HIV-infected persons.
30933973	5	91	from	half	952:955	arg1	split					943:947	split	943:947	split	943:947	The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation.
30933973	5	91	from	half	952:955	arg1	dataset					931:937	The dataset	927:937	The dataset	927:937	The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation.
30933973	4	92	theme	rank	835:838	arg1	features					843:850	rank AA features	835:850	rank AA features	835:850	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	4	93	theme	gp160	692:696	arg1	pseudoviruses					698:710	611 HIV-1 gp160 pseudoviruses	682:710	611 HIV-1 gp160 pseudoviruses from the CATNAP database	682:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	2	94	theme	HIV-1	356:360	arg1	AA					389:390	AA	389:390	AA	389:390	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	2	94	theme	HIV-1	356:360	arg1	acid					383:386	HIV-1 envelope (Env) amino acid	356:386	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	4	95	from	features	670:677	arg1	database					728:735	the CATNAP database	717:735	the CATNAP database	717:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	4	96	theme	regression	907:916	arg1	methods					918:924	classification and regression methods	888:924	methods	918:924	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	4	97	theme	AA	658:659	arg1	features					670:677	Env AA sequence features	654:677	Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database	654:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	0	98	theme	neutralization	20:33	arg1	sensitivity					35:45	VRC01 neutralization sensitivity	14:45	VRC01 neutralization sensitivity	14:45	Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.
30933973	1	99	theme	antibody	106:113	arg1	VRC01					122:126	The broadly neutralizing antibody (bnAb) VRC01	81:126	The broadly neutralizing antibody (bnAb) VRC01	81:126	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30933973	2	100	theme	acid	383:386	arg1	features					402:409	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	HIV-1 envelope (Env) amino acid (AA) sequence features	356:409	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	3	101	contain	have	513:516	arg1	feature					473:479	every AA feature	464:479	every AA feature with sufficient variation	464:505	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	3	101	contain	have	513:516	arg2	power					534:538	low statistical power	518:538	low statistical power	518:538	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	4	102	theme	features	670:677	arg1	neutralization					622:635	VRC01 neutralization	616:635	VRC01 neutralization	616:635	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	4	102	theme	features	670:677	arg1	function					642:649	a function	640:649	a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database	640:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	9	103	from	sites	1840:1844	arg1	gp120					1762:1766	gp120	1762:1766	gp120	1762:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	103	from	sites	1840:1844	arg1	Env					1796:1798	Env	1796:1798	Env	1796:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	8	104	theme	log	1491:1493	arg1	IC50					1495:1498	Quantitative log IC50	1478:1498	Quantitative log IC50	1478:1498	Quantitative log IC50 was predicted with an average validated R2 of 0.355.
30933973	3	105	with	feature	473:479	arg1	variation					497:505	sufficient variation	486:505	sufficient variation	486:505	An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power.
30933973	7	106	theme	0.868	1438:1442	arg1	AUC					1431:1433	an average validated AUC	1410:1433	an average validated AUC of 0.868 across the two hold-out datasets	1410:1475	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	4	107	theme	classification	888:901	arg1	methods					918:924	classification and regression methods	888:924	methods	918:924	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	9	108	from	number	1739:1744	arg1	gp120					1762:1766	gp120	1762:1766	gp120	1762:1766	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	9	108	from	number	1739:1744	arg1	Env					1796:1798	Env	1796:1798	Env	1796:1798	Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis.
30933973	2	109	theme	VRC01	313:317	arg1	PE					340:341	PE	340:341	PE	340:341	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	2	109	theme	VRC01	313:317	arg1	efficacy					330:337	VRC01 prevention efficacy	313:337	VRC01 prevention efficacy (PE)	313:342	A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features.
30933973	7	110	with	right-censored	1366:1379	arg1	AUC					1431:1433	an average validated AUC	1410:1433	an average validated AUC of 0.868 across the two hold-out datasets	1410:1475	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	1	111	theme	Prevention	216:225	arg1	trials					233:238	the Antibody Mediated Prevention (AMP) trials	194:238	the Antibody Mediated Prevention (AMP) trials	194:238	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30933973	7	112	theme	average	1413:1419	arg1	AUC					1431:1433	an average validated AUC	1410:1433	an average validated AUC of 0.868 across the two hold-out datasets	1410:1475	This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets.
30933973	8	113	theme	average	1522:1528	arg1	R2					1540:1541	an average validated R2	1519:1541	an average validated R2 of 0.355	1519:1550	Quantitative log IC50 was predicted with an average validated R2 of 0.355.
30933973	4	114	theme	CATNAP	721:726	arg1	database					728:735	the CATNAP database	717:735	the CATNAP database	717:735	To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods.
30933973	1	115	theme	AMP	228:230	arg1	trials					233:238	the Antibody Mediated Prevention (AMP) trials	194:238	the Antibody Mediated Prevention (AMP) trials	194:238	The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials.
30982611	10	0	theme	genetic	1880:1886	arg1	syndrome					1888:1895	a genetic syndrome	1878:1895	a genetic syndrome	1878:1895	Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
30982611	2	1	theme	hemizygous	366:375	arg1	variant					388:394	a hemizygous truncating variant	364:394	a hemizygous truncating variant in the gene encoding glypican 4 (GPC4)	364:433	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	3	2	theme	anchor	702:707	arg1	sites					718:722	functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	608:722	functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	608:722	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	4	3	theme	predicted	818:826	arg1	variants					839:846	novel and predicted pathogenic variants	808:846	novel and predicted pathogenic variants in GPC4	808:854	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	3	4	theme	GPI	697:699	arg1	Ser529					710:715	Ser529	710:715	Ser529	710:715	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	4	theme	GPI	697:699	arg1	anchor					702:707	glycosylphosphatidylinositol (GPI) anchor	667:707	glycosylphosphatidylinositol (GPI) anchor (Ser529)	667:716	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	5	from	exon	471:474	arg1	located					450:456	located	450:456	located	450:456	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	2	6	theme	Australian	275:284	arg1	family					286:291	the Australian family	271:291	the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome)	271:351	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	9	7	theme	Keipert	1692:1698	arg1	syndrome					1700:1707	Keipert syndrome	1692:1707	Keipert syndrome	1692:1707	Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
30982611	3	8	theme	sites	718:722	arg1	loss					600:603	concomitant loss	588:603	concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	588:722	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	9	theme	prior	556:560	arg1	residues					547:554	the protein 51 amino acid residues	521:554	the protein 51 amino acid residues prior to the stop codon	521:578	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	5	10	theme	Segregation	857:867	arg1	analysis					869:876	Segregation analysis	857:876	Segregation analysis	857:876	Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition.
30982611	2	11	from	variant	388:394	arg1	gene					403:406	the gene	399:406	the gene encoding glypican 4 (GPC4)	399:433	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	3	12	theme	acid	542:545	arg1	residues					547:554	the protein 51 amino acid residues	521:554	the protein 51 amino acid residues prior to the stop codon	521:578	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	10	13	theme	function	1782:1789	arg1	loss					1774:1777	a loss	1772:1777	a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome	1772:1895	Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
30982611	8	14	theme	features	1453:1460	arg1	evidence					1425:1432	evidence	1425:1432	evidence of the two primary features of Keipert syndrome	1425:1480	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	7	15	theme	variable	1369:1376	arg1	features					1378:1385	variable features	1369:1385	variable features	1369:1385	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	4	16	from	kindreds	794:801	arg1	males					767:771	seven affected males	752:771	seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4	752:854	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	5	17	theme	carrier	908:914	arg1	females					916:922	carrier females	908:922	carrier females	908:922	Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition.
30982611	8	18	theme	Keipert	1465:1471	arg1	syndrome					1473:1480	Keipert syndrome	1465:1480	Keipert syndrome	1465:1480	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	3	19	theme	concomitant	588:598	arg1	loss					600:603	concomitant loss	588:603	concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	588:722	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	1	20	theme	growth-factor	135:147	arg1	signaling					149:157	growth-factor signaling	135:157	growth-factor signaling	135:157	Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis.
30982611	2	21	theme	Whole-exome	245:255	arg1	sequencing					257:266	Whole-exome sequencing	245:266	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome)	245:351	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	9	22	theme	Phylogenetic	1537:1548	arg1	analysis					1550:1557	Phylogenetic analysis	1537:1557	Phylogenetic analysis	1537:1557	Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
30982611	6	23	theme	functional	1011:1020	arg1	studies					1022:1028	functional studies	1011:1028	functional studies of recombinant protein	1011:1051	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	8	24	theme	digital	1514:1520	arg1	abnormalities					1522:1534	digital abnormalities	1514:1534	digital abnormalities	1514:1534	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	7	25	dep	included	1190:1197	arg1	whereas					1322:1328	whereas	1322:1328	whereas	1322:1328	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	4	26	with	males	767:771	arg1	variants					839:846	novel and predicted pathogenic variants	808:846	novel and predicted pathogenic variants in GPC4	808:854	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	4	27	from	variants	839:846	arg1	GPC4					851:854	GPC4	851:854	GPC4	851:854	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	5	28	from	analysis	869:876	arg1	females					916:922	carrier females	908:922	carrier females	908:922	Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition.
30982611	7	29	theme	cognitive	1330:1338	arg1	impairment					1340:1349	cognitive impairment	1330:1349	cognitive impairment	1330:1349	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	6	30	dep	proteins	1082:1089	arg1	proteins					1082:1089	the truncated proteins p.Gln506∗ and p.Glu496∗	1068:1113	the truncated proteins p.Gln506∗ and p.Glu496∗	1068:1113	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	6	30	dep	proteins	1082:1089	arg1	p.Glu496∗					1105:1113	p.Glu496∗	1105:1113	p.Glu496∗	1105:1113	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	6	30	dep	proteins	1082:1089	arg1	p.Gln506∗					1091:1099	p.Gln506∗	1091:1099	p.Gln506∗	1091:1099	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	9	31	contain	has	1662:1664	arg2	phenotypic					1668:1677	phenotypic	1668:1677	phenotypic	1668:1677	Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
30982611	9	31	contain	has	1662:1664	arg1	dysplasia					1647:1655	a bone dysplasia	1640:1655	a bone dysplasia that has a phenotypic overlap with Keipert syndrome	1640:1707	Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
30982611	0	32	theme	Pathogenic	0:9	arg1	Variants					11:18	Pathogenic Variants	0:18	Pathogenic Variants in GPC4	0:26	Pathogenic Variants in GPC4 Cause Keipert Syndrome.
30982611	1	33	theme	cell-surface	78:89	arg1	proteoglycans					107:119	cell-surface heparan sulfate proteoglycans	78:119	cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis	78:242	Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis.
30982611	6	34	theme	truncated	1072:1080	arg1	proteins					1082:1089	the truncated proteins p.Gln506∗ and p.Glu496∗	1068:1113	the truncated proteins p.Gln506∗ and p.Glu496∗	1068:1113	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	6	34	theme	truncated	1072:1080	arg1	p.Glu496∗					1105:1113	p.Glu496∗	1105:1113	p.Glu496∗	1105:1113	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	6	34	theme	truncated	1072:1080	arg1	stable					1125:1130	stable	1125:1130	stable	1125:1130	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	6	34	theme	truncated	1072:1080	arg1	p.Gln506∗					1091:1099	p.Gln506∗	1091:1099	p.Gln506∗	1091:1099	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	7	35	theme	syndrome	1181:1188	arg1	features					1161:1168	Clinical features	1152:1168	Clinical features of Keipert syndrome	1152:1188	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	10	36	theme	pathogenic	1738:1747	arg1	variants					1749:1756	pathogenic variants	1738:1756	pathogenic variants in GPC4	1738:1764	Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
30982611	1	37	theme	sulfate	99:105	arg1	proteoglycans					107:119	cell-surface heparan sulfate proteoglycans	78:119	cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis	78:242	Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis.
30982611	7	38	theme	digital	1299:1305	arg1	abnormalities					1307:1319	digital abnormalities	1299:1319	digital abnormalities	1299:1319	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	3	39	theme	important	621:629	arg1	glycosylation					640:652	functionally important N-linked glycosylation	608:652	functionally important N-linked glycosylation (Asn514)	608:661	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	39	theme	important	621:629	arg1	Asn514					655:660	Asn514	655:660	Asn514	655:660	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	8	40	theme	Gpc4	1399:1402	arg1	mice					1413:1416	Gpc4 knockout mice	1399:1416	Gpc4 knockout mice	1399:1416	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	3	41	theme	located	450:456	arg1	variant					441:447	This variant	436:447	This variant	436:447	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	6	42	theme	protein	1045:1051	arg1	studies					1022:1028	functional studies	1011:1028	functional studies of recombinant protein	1011:1051	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	4	43	theme	novel	808:812	arg1	variants					839:846	novel and predicted pathogenic variants	808:846	novel and predicted pathogenic variants in GPC4	808:854	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	3	44	theme	GPC4	479:482	arg1	exon					471:474	the final exon	461:474	the final exon of GPC4	461:482	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	7	45	theme	Clinical	1152:1159	arg1	features					1161:1168	Clinical features	1152:1168	Clinical features of Keipert syndrome	1152:1188	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	6	46	theme	wild	1141:1144	arg1	type					1146:1149	the wild type	1137:1149	the wild type	1137:1149	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	3	47	link	N-linked	631:638	arg1	glycosylation					640:652	functionally important N-linked glycosylation	608:652	functionally important N-linked glycosylation (Asn514)	608:661	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	47	link	N-linked	631:638	arg1	Asn514					655:660	Asn514	655:660	Asn514	655:660	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	7	48	theme	downturned	1266:1275	arg1	nose					1260:1263	a broad nose	1252:1263	a broad nose	1252:1263	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	7	48	theme	downturned	1266:1275	arg1	corners					1277:1283	downturned corners	1266:1283	downturned corners of mouth	1266:1292	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	3	49	theme	glycosylation	640:652	arg1	sites					718:722	functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	608:722	functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	608:722	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	50	theme	premature	496:504	arg1	termination					506:516	premature termination	496:516	premature termination of the protein 51 amino acid residues prior to the stop codon	496:578	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	1	51	theme	morphogenesis	230:242	arg1	regulation					216:225	the regulation	212:225	the regulation of morphogenesis	212:242	Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis.
30982611	9	52	dep	phenotypic	1668:1677	arg1	overlap					1679:1685	overlap	1679:1685	overlap	1679:1685	Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
30982611	2	53	theme	truncating	377:386	arg1	variant					388:394	a hemizygous truncating variant	364:394	a hemizygous truncating variant in the gene encoding glypican 4 (GPC4)	364:433	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	8	54	theme	mice	1413:1416	arg1	Studies					1388:1394	Studies	1388:1394	Studies of Gpc4 knockout mice	1388:1416	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	3	55	theme	protein	525:531	arg1	residues					547:554	the protein 51 amino acid residues	521:554	the protein 51 amino acid residues prior to the stop codon	521:578	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	2	56	theme	nasodigitoacoustic	324:341	arg1	syndrome					314:321	Keipert syndrome	306:321	Keipert syndrome (nasodigitoacoustic syndrome)	306:351	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	2	56	theme	nasodigitoacoustic	324:341	arg1	syndrome					343:350	nasodigitoacoustic syndrome	324:350	nasodigitoacoustic syndrome	324:350	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	2	57	theme	family	286:291	arg1	sequencing					257:266	Whole-exome sequencing	245:266	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome)	245:351	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	3	58	theme	residues	547:554	arg1	termination					506:516	premature termination	496:516	premature termination of the protein 51 amino acid residues prior to the stop codon	496:578	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	4	59	theme	pathogenic	828:837	arg1	variants					839:846	novel and predicted pathogenic variants	808:846	novel and predicted pathogenic variants in GPC4	808:854	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	3	60	theme	amino	536:540	arg1	residues					547:554	the protein 51 amino acid residues	521:554	the protein 51 amino acid residues prior to the stop codon	521:578	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	8	61	theme	primary	1445:1451	arg1	features					1453:1460	the two primary features	1437:1460	the two primary features of Keipert syndrome	1437:1480	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	3	62	theme	stop	569:572	arg1	codon					574:578	the stop codon	565:578	the stop codon	565:578	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	1	63	theme	proteoglycans	107:119	arg1	Glypicans					52:60	Glypicans	52:60	Glypicans	52:60	Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis.
30982611	1	63	theme	proteoglycans	107:119	arg1	family					68:73	a family	66:73	a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis	66:242	Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis.
30982611	10	64	theme	human	1847:1851	arg1	glypican					1853:1860	the third human glypican	1837:1860	the third human glypican	1837:1860	Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
30982611	8	65	theme	syndrome	1473:1480	arg1	features					1453:1460	the two primary features	1437:1460	the two primary features of Keipert syndrome	1437:1480	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	10	66	from	variants	1749:1756	arg1	GPC4					1761:1764	GPC4	1761:1764	GPC4	1761:1764	Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
30982611	6	67	theme	recombinant	1033:1043	arg1	protein					1045:1051	recombinant protein	1033:1051	recombinant protein	1033:1051	Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type.
30982611	8	68	theme	craniofacial	1483:1494	arg1	abnormalities					1496:1508	craniofacial abnormalities	1483:1508	craniofacial abnormalities	1483:1508	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	7	69	theme	flat	1223:1226	arg1	midface					1228:1234	a flat midface	1221:1234	a flat midface	1221:1234	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	5	70	theme	X-inactivation	882:895	arg1	studies					897:903	X-inactivation studies	882:903	X-inactivation studies	882:903	Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition.
30982611	0	71	from	Variants	11:18	arg1	GPC4					23:26	GPC4	23:26	GPC4	23:26	Pathogenic Variants in GPC4 Cause Keipert Syndrome.
30982611	5	72	from	studies	897:903	arg1	females					916:922	carrier females	908:922	carrier females	908:922	Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition.
30982611	5	73	theme	GPC4	962:965	arg1	variants					967:974	the GPC4 variants	958:974	the GPC4 variants	958:974	Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition.
30982611	2	74	theme	Keipert	306:312	arg1	syndrome					314:321	Keipert syndrome	306:321	Keipert syndrome (nasodigitoacoustic syndrome)	306:351	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	2	74	theme	Keipert	306:312	arg1	syndrome					343:350	nasodigitoacoustic syndrome	324:350	nasodigitoacoustic syndrome	324:350	Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4).
30982611	7	75	theme	prominent	1201:1209	arg1	forehead					1211:1218	a prominent forehead	1199:1218	a prominent forehead	1199:1218	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	5	76	theme	supportive	933:942	arg1	evidence					944:951	supportive evidence that the GPC4 variants caused the condition	933:995	supportive evidence that the GPC4 variants caused the condition	933:995	Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition.
30982611	7	77	theme	Keipert	1173:1179	arg1	syndrome					1181:1188	Keipert syndrome	1173:1188	Keipert syndrome	1173:1188	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	1	78	theme	heparan	91:97	arg1	proteoglycans					107:119	cell-surface heparan sulfate proteoglycans	78:119	cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis	78:242	Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis.
30982611	10	79	theme	Keipert	1807:1813	arg1	syndrome					1815:1822	Keipert syndrome	1807:1822	Keipert syndrome	1807:1822	Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
30982611	3	80	theme	final	465:469	arg1	exon					471:474	the final exon	461:474	the final exon of GPC4	461:482	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	0	81	theme	Keipert	34:40	arg1	Syndrome					42:49	Keipert Syndrome	34:49	Keipert Syndrome	34:49	Pathogenic Variants in GPC4 Cause Keipert Syndrome.
30982611	7	82	theme	mouth	1288:1292	arg1	nose					1260:1263	a broad nose	1252:1263	a broad nose	1252:1263	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	7	82	theme	mouth	1288:1292	arg1	corners					1277:1283	downturned corners	1266:1283	downturned corners of mouth	1266:1292	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	10	83	theme	third	1841:1845	arg1	glypican					1853:1860	the third human glypican	1837:1860	the third human glypican	1837:1860	Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.
30982611	4	84	theme	additional	783:792	arg1	kindreds					794:801	five additional kindreds	778:801	five additional kindreds	778:801	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	3	85	from	located	450:456	arg1	exon					471:474	the final exon	461:474	the final exon of GPC4	461:482	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	8	86	theme	knockout	1404:1411	arg1	mice					1413:1416	Gpc4 knockout mice	1399:1416	Gpc4 knockout mice	1399:1416	Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities.
30982611	3	87	theme	N-linked	631:638	arg1	glycosylation					640:652	functionally important N-linked glycosylation	608:652	functionally important N-linked glycosylation (Asn514)	608:661	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	87	theme	N-linked	631:638	arg1	Asn514					655:660	Asn514	655:660	Asn514	655:660	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	4	88	theme	affected	758:765	arg1	males					767:771	seven affected males	752:771	seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4	752:854	We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4.
30982611	9	89	theme	bone	1642:1645	arg1	dysplasia					1647:1655	a bone dysplasia	1640:1655	a bone dysplasia that has a phenotypic overlap with Keipert syndrome	1640:1707	Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
30982611	7	90	theme	broad	1254:1258	arg1	nose					1260:1263	a broad nose	1252:1263	a broad nose	1252:1263	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	7	90	theme	broad	1254:1258	arg1	corners					1277:1283	downturned corners	1266:1283	downturned corners of mouth	1266:1292	Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features.
30982611	3	91	gly	glycosylation	640:652	arg2	sites					718:722	functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	608:722	functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites	608:722	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	92	theme	glycosylphosphatidylinositol	667:694	arg1	Ser529					710:715	Ser529	710:715	Ser529	710:715	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	3	92	theme	glycosylphosphatidylinositol	667:694	arg1	anchor					702:707	glycosylphosphatidylinositol (GPI) anchor	667:707	glycosylphosphatidylinositol (GPI) anchor (Ser529)	667:716	This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites.
30982611	9	93	with	phenotypic	1668:1677	arg1	syndrome					1700:1707	Keipert syndrome	1692:1707	Keipert syndrome	1692:1707	Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome.
29263266	4	0	theme	number	824:829	arg1	upregulation					806:817	the upregulation	802:817	the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages	802:892	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	6	1	theme	surface	1044:1050	arg1	moieties					1063:1070	cell surface galactosyl moieties	1039:1070	cell surface galactosyl moieties	1039:1070	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	8	2	theme	target	1590:1595	arg1	cells					1597:1601	target cells	1590:1601	target cells	1590:1601	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	10	3	theme	important	1847:1855	arg1	category					1857:1864	another important category	1839:1864	another important category of carbohydrate-binding proteins (CBP)	1839:1903	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	10	3	theme	important	1847:1855	arg1	Lectins					1751:1757	Lectins	1751:1757	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity	1751:1833	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	4	4	theme	antiviral	834:842	arg1	ISGs					873:876	ISGs	873:876	ISGs	873:876	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	4	4	theme	antiviral	834:842	arg1	genes					866:870	antiviral interferon-stimulated genes	834:870	antiviral interferon-stimulated genes (ISGs) in macrophages	834:892	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	6	5	theme	antiviral	1163:1171	arg1	factors					1173:1179	the antiviral factors	1159:1179	the antiviral factors	1159:1179	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	3	6	theme	virus	683:687	arg1	cycle					711:715	the virus infection/replication cycle	679:715	the virus infection/replication cycle	679:715	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	8	7	dep	SBL	1447:1449	arg1	block					1559:1563	block	1559:1563	can block the attachment of HIV to target cells	1555:1601	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	10	8	theme	proteins	1890:1897	arg1	category					1857:1864	another important category	1839:1864	another important category of carbohydrate-binding proteins (CBP)	1839:1903	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	10	8	theme	proteins	1890:1897	arg1	Lectins					1751:1757	Lectins	1751:1757	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity	1751:1833	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	7	9	theme	anti-HIV	1357:1364	arg1	agent					1366:1370	a potential anti-HIV agent	1345:1370	a potential anti-HIV agent compared with MBLs	1345:1389	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	4	10	theme	interferon-stimulated	844:864	arg1	ISGs					873:876	ISGs	873:876	ISGs	873:876	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	4	10	theme	interferon-stimulated	844:864	arg1	genes					866:870	antiviral interferon-stimulated genes	834:870	antiviral interferon-stimulated genes (ISGs) in macrophages	834:892	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	1	11	theme	significant	185:195	arg1	activity					197:204	significant activity	185:204	significant activity against HIV infection	185:226	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	12	12	theme	GalNAc-specific	2049:2063	arg1	SBL					2081:2083	SBL	2081:2083	SBL	2081:2083	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	12	12	theme	GalNAc-specific	2049:2063	arg1	lectin					2073:2078	GalNAc-specific soybean lectin	2049:2078	GalNAc-specific soybean lectin (SBL)	2049:2084	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	3	13	theme	cycle	711:715	arg1	steps					670:674	multiple steps	661:674	multiple steps of the virus infection/replication cycle	661:715	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	1	14	contain	have	306:309	arg1	lectins					298:304	N-acetylgalactosamine (GalNAc)-binding lectins	259:304	N-acetylgalactosamine (GalNAc)-binding lectins	259:304	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	1	14	contain	have	306:309	arg2	ability					315:321	the ability to inhibit HIV infection	311:346	the ability to inhibit HIV infection	311:346	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	9	15	theme	mitogenic	1666:1674	arg1	effect					1676:1681	the mitogenic effect	1662:1681	the mitogenic effect of MBLs on CD4+ T cells	1662:1705	However, the mitogenic effect of MBLs on CD4+ T cells limits this potential in clinical settings.
29263266	7	16	theme	SBL	1338:1340	arg1	development					1323:1333	the development	1319:1333	the development of SBL as a potential anti-HIV agent compared with MBLs	1319:1389	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	3	17	theme	envelope	591:598	arg1	gp41					620:623	gp41	620:623	gp41	620:623	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	17	theme	envelope	591:598	arg1	gp120					610:614	gp120	610:614	gp120	610:614	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	17	theme	envelope	591:598	arg1	proteins					600:607	the glycosylated envelope proteins	574:607	the glycosylated envelope proteins (gp120 and gp41) of the virus	574:637	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	4	18	theme	genes	866:870	arg1	number					824:829	a number	822:829	a number of antiviral interferon-stimulated genes (ISGs) in macrophages	822:892	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	13	19	theme	anti-HIV	2408:2415	arg1	agents					2417:2422	naturopathic anti-HIV agents	2395:2422	naturopathic anti-HIV agents	2395:2422	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	4	20	from	genes	866:870	arg1	macrophages					882:892	macrophages	882:892	macrophages	882:892	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	9	21	theme	T	1699:1699	arg1	cells					1701:1705	CD4+ T cells	1694:1705	CD4+ T cells	1694:1705	However, the mitogenic effect of MBLs on CD4+ T cells limits this potential in clinical settings.
29263266	7	22	theme	major	1300:1304	arg1	advantage					1306:1314	a major advantage	1298:1314	a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs	1298:1389	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	7	23	theme	anti-HIV	1211:1218	arg1	activity					1220:1227	its anti-HIV activity	1207:1227	its anti-HIV activity in the low nanomolar range	1207:1254	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	11	24	theme	N-linked	1931:1938	arg1	glycans					1940:1946	high-mannose N-linked glycans	1918:1946	high-mannose N-linked glycans	1918:1946	Compared to high-mannose N-linked glycans, GalNAc-type glycans present much less in HIV gp120 or gp41 glycosylation.
29263266	1	25	theme	mannose-binding	146:160	arg1	MBLs					171:174	MBLs	171:174	MBLs	171:174	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	1	25	theme	mannose-binding	146:160	arg1	lectins					162:168	some mannose-binding lectins	141:168	some mannose-binding lectins (MBLs)	141:175	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	4	26	from	number	824:829	arg1	macrophages					882:892	macrophages	882:892	macrophages	882:892	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	5	27	theme	entry	997:1001	arg1	CCR5					1014:1017	HIV entry coreceptor CCR5	993:1017	HIV entry coreceptor CCR5	993:1017	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	9	28	from	effect	1676:1681	arg1	cells					1701:1705	CD4+ T cells	1694:1705	CD4+ T cells	1694:1705	However, the mitogenic effect of MBLs on CD4+ T cells limits this potential in clinical settings.
29263266	0	29	theme	Factors	100:106	arg1	Induction					77:85	Induction	77:85	Induction of Antiviral Factors	77:106	GalNAc-Specific Soybean Lectin Inhibits HIV Infection of Macrophages through Induction of Antiviral Factors.
29263266	9	30	theme	clinical	1732:1739	arg1	settings					1741:1748	clinical settings	1732:1748	clinical settings	1732:1748	However, the mitogenic effect of MBLs on CD4+ T cells limits this potential in clinical settings.
29263266	4	31	theme	interferon	746:755	arg1	pathway					780:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	13	32	theme	Gal/GalNAc-specific	2364:2382	arg1	lectins					2384:2390	Gal/GalNAc-specific lectins	2364:2390	Gal/GalNAc-specific lectins as naturopathic anti-HIV agents	2364:2422	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	8	33	theme	anti-HIV	1488:1495	arg1	product.IMPORTANCE					1505:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE	1454:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs)	1454:1553	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	2	34	theme	dose-dependent	493:506	arg1	fashion					508:514	a dose-dependent fashion	491:514	a dose-dependent fashion	491:514	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	12	35	theme	group	2162:2166	arg1	recognition					2119:2129	recognition	2119:2129	recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps	2119:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	0	36	theme	GalNAc-Specific	0:14	arg1	Lectin					24:29	GalNAc-Specific Soybean Lectin	0:29	GalNAc-Specific Soybean Lectin	0:29	GalNAc-Specific Soybean Lectin Inhibits HIV Infection of Macrophages through Induction of Antiviral Factors.
29263266	13	37	theme	major	2326:2330	arg1	advantage					2332:2340	a major advantage	2324:2340	a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents	2324:2422	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	12	38	from	steps	2236:2240	arg1	suppression					2205:2215	the suppression	2201:2215	the suppression of HIV at multiple steps	2201:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	8	39	theme	product.IMPORTANCE	1505:1522	arg1	lectins					1540:1546	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins	1454:1546	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs)	1454:1553	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	8	39	theme	product.IMPORTANCE	1505:1522	arg1	MBLs					1549:1552	MBLs	1549:1552	MBLs	1549:1552	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	12	40	theme	macrophages	2171:2181	arg1	macrophages					2171:2181	macrophages	2171:2181	macrophages	2171:2181	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	12	40	theme	macrophages	2171:2181	arg1	group					2162:2166	the cell surface galactosyl group	2134:2166	the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps	2134:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	13	41	theme	CD4+	2310:2313	arg1	cells					2317:2321	CD4+ T cells	2310:2321	CD4+ T cells	2310:2321	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	1	42	theme	-binding	289:296	arg1	lectins					298:304	N-acetylgalactosamine (GalNAc)-binding lectins	259:304	N-acetylgalactosamine (GalNAc)-binding lectins	259:304	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	5	43	theme	SBL	908:910	arg1	treatment					912:920	SBL treatment	908:920	SBL treatment of macrophages	908:935	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	7	44	theme	CD4+	1284:1287	arg1	cells					1291:1295	CD4+ T cells	1284:1295	CD4+ T cells	1284:1295	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	0	45	theme	HIV	40:42	arg1	Infection					44:52	HIV Infection	40:52	HIV Infection of Macrophages	40:67	GalNAc-Specific Soybean Lectin Inhibits HIV Infection of Macrophages through Induction of Antiviral Factors.
29263266	13	46	contain	has	2265:2267	arg2	effect					2282:2287	no mitogenic effect	2269:2287	no mitogenic effect	2269:2287	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	13	46	contain	has	2265:2267	arg1	SBL					2261:2263	SBL	2261:2263	SBL	2261:2263	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	13	46	contain	has	2265:2267	arg2	advantage					2332:2340	a major advantage	2324:2340	a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents	2324:2422	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	13	47	theme	T	2315:2315	arg1	cells					2317:2321	CD4+ T cells	2310:2321	CD4+ T cells	2310:2321	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	2	48	theme	HIV	459:461	arg1	infection					463:471	HIV infection	459:471	HIV infection of macrophages	459:486	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	6	49	gly	Deglycosylation	1020:1034	arg1	presaturation					1075:1087	presaturation	1075:1087	presaturation of GalNAc-binding capacity	1075:1114	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	6	49	gly	Deglycosylation	1020:1034	arg1	moieties					1063:1070	cell surface galactosyl moieties	1039:1070	cell surface galactosyl moieties	1039:1070	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	2	50	link	soybean-derived	377:391	arg1	SBL					401:403	SBL	401:403	SBL	401:403	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	2	50	link	soybean-derived	377:391	arg1	lectin					393:398	a soybean-derived lectin	375:398	a soybean-derived lectin (SBL) with GalNAc-binding affinity	375:433	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	12	51	theme	surface	2143:2149	arg1	macrophages					2171:2181	macrophages	2171:2181	macrophages	2171:2181	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	12	51	theme	surface	2143:2149	arg1	group					2162:2166	the cell surface galactosyl group	2134:2166	the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps	2134:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	4	52	theme	IFN-β	758:762	arg1	pathway					780:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	4	53	theme	-STAT	764:768	arg1	pathway					780:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	5	54	theme	C-C	963:965	arg1	chemokines					967:976	C-C chemokines	963:976	C-C chemokines	963:976	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	7	55	theme	low	1236:1238	arg1	range					1250:1254	the low nanomolar range	1232:1254	the low nanomolar range	1232:1254	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	8	56	theme	anti-HIV	1630:1637	arg1	microbicides					1639:1650	anti-HIV microbicides	1630:1650	anti-HIV microbicides	1630:1650	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	8	56	theme	anti-HIV	1630:1637	arg1	data					1398:1401	These data	1392:1401	These data	1392:1401	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	2	57	with	lectin	393:398	arg1	affinity					426:433	GalNAc-binding affinity	411:433	GalNAc-binding affinity	411:433	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	7	58	from	activity	1220:1227	arg1	range					1250:1254	the low nanomolar range	1232:1254	the low nanomolar range	1232:1254	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	6	59	theme	cell	1039:1042	arg1	moieties					1063:1070	cell surface galactosyl moieties	1039:1070	cell surface galactosyl moieties	1039:1070	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	6	60	theme	SBL-mediated	1133:1144	arg1	induction					1146:1154	SBL-mediated induction	1133:1154	SBL-mediated induction of the antiviral factors	1133:1179	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	12	61	theme	HIV	2220:2222	arg1	suppression					2205:2215	the suppression	2201:2215	the suppression of HIV at multiple steps	2201:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	3	62	theme	infection/replication	689:709	arg1	cycle					711:715	the virus infection/replication cycle	679:715	the virus infection/replication cycle	679:715	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	11	63	theme	GalNAc-type	1949:1959	arg1	glycans					1961:1967	GalNAc-type glycans	1949:1967	GalNAc-type glycans	1949:1967	Compared to high-mannose N-linked glycans, GalNAc-type glycans present much less in HIV gp120 or gp41 glycosylation.
29263266	10	64	theme	carbohydrate-binding	1869:1888	arg1	proteins					1890:1897	carbohydrate-binding proteins	1869:1897	carbohydrate-binding proteins (CBP)	1869:1903	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	10	64	theme	carbohydrate-binding	1869:1888	arg1	CBP					1900:1902	CBP	1900:1902	CBP	1900:1902	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	11	65	theme	HIV	1990:1992	arg1	gp120					1994:1998	HIV gp120	1990:1998	HIV gp120	1990:1998	Compared to high-mannose N-linked glycans, GalNAc-type glycans present much less in HIV gp120 or gp41 glycosylation.
29263266	13	66	theme	mitogenic	2272:2280	arg1	effect					2282:2287	no mitogenic effect	2269:2287	no mitogenic effect	2269:2287	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	10	67	with	Lectins	1751:1757	arg1	specificity					1823:1833	galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity	1764:1833	galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity	1764:1833	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	3	68	dep	proteins	600:607	arg1	gp41					620:623	gp41	620:623	gp41	620:623	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	68	dep	proteins	600:607	arg1	gp120					610:614	gp120	610:614	gp120	610:614	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	68	dep	proteins	600:607	arg1	proteins					600:607	the glycosylated envelope proteins	574:607	the glycosylated envelope proteins (gp120 and gp41) of the virus	574:637	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	6	69	theme	capacity	1107:1114	arg1	presaturation					1075:1087	presaturation	1075:1087	presaturation of GalNAc-binding capacity	1075:1114	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	6	69	theme	capacity	1107:1114	arg1	moieties					1063:1070	cell surface galactosyl moieties	1039:1070	cell surface galactosyl moieties	1039:1070	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	3	70	gly	glycosylated	578:589	arg1	gp41					620:623	gp41	620:623	gp41	620:623	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	70	gly	glycosylated	578:589	arg1	gp120					610:614	gp120	610:614	gp120	610:614	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	70	gly	glycosylated	578:589	arg1	proteins					600:607	the glycosylated envelope proteins	574:607	the glycosylated envelope proteins (gp120 and gp41) of the virus	574:637	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	4	71	from	macrophages	882:892	arg1	number					824:829	a number	822:829	a number of antiviral interferon-stimulated genes (ISGs) in macrophages	822:892	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	3	72	theme	glycosylated	578:589	arg1	gp41					620:623	gp41	620:623	gp41	620:623	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	72	theme	glycosylated	578:589	arg1	gp120					610:614	gp120	610:614	gp120	610:614	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	72	theme	glycosylated	578:589	arg1	proteins					600:607	the glycosylated envelope proteins	574:607	the glycosylated envelope proteins (gp120 and gp41) of the virus	574:637	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	1	73	theme	HIV	214:216	arg1	infection					218:226	HIV infection	214:226	HIV infection	214:226	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	11	74	theme	gp41	2003:2006	arg1	glycosylation					2008:2020	gp41 glycosylation	2003:2020	gp41 glycosylation	2003:2020	Compared to high-mannose N-linked glycans, GalNAc-type glycans present much less in HIV gp120 or gp41 glycosylation.
29263266	12	75	theme	soybean	2065:2071	arg1	SBL					2081:2083	SBL	2081:2083	SBL	2081:2083	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	12	75	theme	soybean	2065:2071	arg1	lectin					2073:2078	GalNAc-specific soybean lectin	2049:2078	GalNAc-specific soybean lectin (SBL)	2049:2084	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	13	76	theme	lectins	2384:2390	arg1	development					2349:2359	the development	2345:2359	the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents	2345:2422	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	9	77	theme	MBLs	1686:1689	arg1	effect					1676:1681	the mitogenic effect	1662:1681	the mitogenic effect of MBLs on CD4+ T cells	1662:1705	However, the mitogenic effect of MBLs on CD4+ T cells limits this potential in clinical settings.
29263266	5	78	dep	induced	937:943	arg1	bind					985:988	bind	985:988	bind to HIV entry coreceptor CCR5	985:1017	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	13	79	from	advantage	2332:2340	arg1	development					2349:2359	the development	2345:2359	the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents	2345:2422	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	13	80	theme	naturopathic	2395:2406	arg1	agents					2417:2422	naturopathic anti-HIV agents	2395:2422	naturopathic anti-HIV agents	2395:2422	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	5	81	theme	HIV	993:995	arg1	CCR5					1014:1017	HIV entry coreceptor CCR5	993:1017	HIV entry coreceptor CCR5	993:1017	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	9	82	theme	CD4+	1694:1697	arg1	cells					1701:1705	CD4+ T cells	1694:1705	CD4+ T cells	1694:1705	However, the mitogenic effect of MBLs on CD4+ T cells limits this potential in clinical settings.
29263266	7	83	theme	nanomolar	1240:1248	arg1	range					1250:1254	the low nanomolar range	1232:1254	the low nanomolar range	1232:1254	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	5	84	theme	coreceptor	1003:1012	arg1	CCR5					1014:1017	HIV entry coreceptor CCR5	993:1017	HIV entry coreceptor CCR5	993:1017	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	11	85	theme	high-mannose	1918:1929	arg1	glycans					1940:1946	high-mannose N-linked glycans	1918:1946	high-mannose N-linked glycans	1918:1946	Compared to high-mannose N-linked glycans, GalNAc-type glycans present much less in HIV gp120 or gp41 glycosylation.
29263266	12	86	theme	multiple	2227:2234	arg1	steps					2236:2240	multiple steps	2227:2240	multiple steps	2227:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	6	87	theme	factors	1173:1179	arg1	induction					1146:1154	SBL-mediated induction	1133:1154	SBL-mediated induction of the antiviral factors	1133:1179	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	0	88	theme	Antiviral	90:98	arg1	Factors					100:106	Antiviral Factors	90:106	Antiviral Factors	90:106	GalNAc-Specific Soybean Lectin Inhibits HIV Infection of Macrophages through Induction of Antiviral Factors.
29263266	1	89	theme	HIV	334:336	arg1	infection					338:346	HIV infection	334:346	HIV infection	334:346	Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection.
29263266	2	90	theme	macrophages	476:486	arg1	infection					463:471	HIV infection	459:471	HIV infection of macrophages	459:486	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	8	91	theme	alternative	1457:1467	arg1	product.IMPORTANCE					1505:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE	1454:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs)	1454:1553	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	10	92	theme	-binding	1814:1821	arg1	specificity					1823:1833	galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity	1764:1833	galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity	1764:1833	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	8	93	attach	attachment	1569:1578	arg2	HIV					1583:1585	HIV	1583:1585	HIV	1583:1585	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	8	93	attach	attachment	1569:1578	arg1	cells					1597:1601	target cells	1590:1601	target cells	1590:1601	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	7	94	theme	potential	1347:1355	arg1	agent					1366:1370	a potential anti-HIV agent	1345:1370	a potential anti-HIV agent compared with MBLs	1345:1389	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	8	95	theme	cost-effective	1473:1486	arg1	product.IMPORTANCE					1505:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE	1454:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs)	1454:1553	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	5	96	theme	macrophages	925:935	arg1	treatment					912:920	SBL treatment	908:920	SBL treatment of macrophages	908:935	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	7	97	from	advantage	1306:1314	arg1	development					1323:1333	the development	1319:1333	the development of SBL as a potential anti-HIV agent compared with MBLs	1319:1389	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	8	98	theme	natural	1497:1503	arg1	product.IMPORTANCE					1505:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE	1454:1522	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs)	1454:1553	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	4	99	theme	beta	741:744	arg1	pathway					780:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	2	100	theme	soybean-derived	377:391	arg1	SBL					401:403	SBL	401:403	SBL	401:403	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	2	100	theme	soybean-derived	377:391	arg1	lectin					393:398	a soybean-derived lectin	375:398	a soybean-derived lectin (SBL) with GalNAc-binding affinity	375:433	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	0	101	theme	Soybean	16:22	arg1	Lectin					24:29	GalNAc-Specific Soybean Lectin	0:29	GalNAc-Specific Soybean Lectin	0:29	GalNAc-Specific Soybean Lectin Inhibits HIV Infection of Macrophages through Induction of Antiviral Factors.
29263266	7	102	theme	T	1289:1289	arg1	cells					1291:1295	CD4+ T cells	1284:1295	CD4+ T cells	1284:1295	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	11	103	link	N-linked	1931:1938	arg1	glycans					1940:1946	high-mannose N-linked glycans	1918:1946	high-mannose N-linked glycans	1918:1946	Compared to high-mannose N-linked glycans, GalNAc-type glycans present much less in HIV gp120 or gp41 glycosylation.
29263266	8	104	theme	Mannose-binding	1524:1538	arg1	lectins					1540:1546	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins	1454:1546	an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs)	1454:1553	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	8	104	theme	Mannose-binding	1524:1538	arg1	MBLs					1549:1552	MBLs	1549:1552	MBLs	1549:1552	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	12	105	theme	galactosyl	2151:2160	arg1	macrophages					2171:2181	macrophages	2171:2181	macrophages	2171:2181	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	12	105	theme	galactosyl	2151:2160	arg1	group					2162:2166	the cell surface galactosyl group	2134:2166	the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps	2134:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	2	106	theme	GalNAc-binding	411:424	arg1	affinity					426:433	GalNAc-binding affinity	411:433	GalNAc-binding affinity	411:433	Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion.
29263266	5	107	theme	chemokines	967:976	arg1	production					949:958	the production	945:958	the production of C-C chemokines	945:976	In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5.
29263266	7	108	theme	mitogenic	1264:1272	arg1	effect					1274:1279	no mitogenic effect	1261:1279	no mitogenic effect on CD4+ T cells	1261:1295	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	4	109	theme	signaling	770:778	arg1	pathway					780:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	the beta interferon (IFN-β)-STAT signaling pathway	737:786	SBL could activate the beta interferon (IFN-β)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages.
29263266	0	110	theme	Macrophages	57:67	arg1	Infection					44:52	HIV Infection	40:52	HIV Infection of Macrophages	40:67	GalNAc-Specific Soybean Lectin Inhibits HIV Infection of Macrophages through Induction of Antiviral Factors.
29263266	13	111	theme	cells	2317:2321	arg1	activation					2296:2305	the activation	2292:2305	the activation of CD4+ T cells	2292:2321	More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
29263266	7	112	from	effect	1274:1279	arg1	cells					1291:1295	CD4+ T cells	1284:1295	CD4+ T cells	1284:1295	Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs.
29263266	6	113	theme	GalNAc-binding	1092:1105	arg1	capacity					1107:1114	GalNAc-binding capacity	1092:1114	GalNAc-binding capacity	1092:1114	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	12	114	theme	cell	2138:2141	arg1	macrophages					2171:2181	macrophages	2171:2181	macrophages	2171:2181	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	12	114	theme	cell	2138:2141	arg1	group					2162:2166	the cell surface galactosyl group	2134:2166	the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps	2134:2240	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	6	115	theme	presaturation	1075:1087	arg1	Deglycosylation					1020:1034	Deglycosylation	1020:1034	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity	1020:1114	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	10	116	dep	-binding	1814:1821	arg1	Gal					1775:1777	Gal	1775:1777	Gal	1775:1777	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	10	116	dep	-binding	1814:1821	arg1	galactose					1764:1772	galactose	1764:1772	galactose	1764:1772	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	10	116	dep	-binding	1814:1821	arg1	N-acetylgalactosamine					1784:1804	N-acetylgalactosamine	1784:1804	N-acetylgalactosamine	1784:1804	Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP).
29263266	3	117	theme	virus	633:637	arg1	gp41					620:623	gp41	620:623	gp41	620:623	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	117	theme	virus	633:637	arg1	gp120					610:614	gp120	610:614	gp120	610:614	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	3	117	theme	virus	633:637	arg1	proteins					600:607	the glycosylated envelope proteins	574:607	the glycosylated envelope proteins (gp120 and gp41) of the virus	574:637	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
29263266	12	118	theme	antiviral	2095:2103	arg1	signaling					2105:2113	antiviral signaling	2095:2113	antiviral signaling	2095:2113	Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps.
29263266	6	119	theme	galactosyl	1052:1061	arg1	moieties					1063:1070	cell surface galactosyl moieties	1039:1070	cell surface galactosyl moieties	1039:1070	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	6	120	theme	moieties	1063:1070	arg1	Deglycosylation					1020:1034	Deglycosylation	1020:1034	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity	1020:1114	Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors.
29263266	8	121	theme	HIV	1583:1585	arg1	attachment					1569:1578	the attachment	1565:1578	the attachment of HIV to target cells	1565:1601	These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides.
29263266	3	122	theme	multiple	661:668	arg1	steps					670:674	multiple steps	661:674	multiple steps of the virus infection/replication cycle	661:715	Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle.
28100911	0	0	theme	dental	71:76	arg1	caries					78:83	dental caries	71:83	dental caries	71:83	Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries.
28100911	1	1	link	N-linked	252:259	arg1	glycoprotein					261:272	small integrin-binding ligand N-linked glycoprotein	222:272	small integrin-binding ligand N-linked glycoprotein	222:272	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	1	link	N-linked	252:259	arg1	ABCG2					193:197	ABCG2	193:197	ABCG2	193:197	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	5	2	dep	rs11938025	905:914	arg1	rs2725270					933:941	rs2725270	933:941	rs2725270	933:941	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	5	2	dep	rs11938025	905:914	arg1	P-value=0.0005					917:930	P-value=0.0005	917:930	P-value=0.0005	917:930	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	1	3	theme	SIBLING	213:219	arg1	family					280:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	8	4	theme	original	1460:1467	arg1	signal					1474:1479	the original GWAS signal	1456:1479	the original GWAS signal	1456:1479	Our results show evidence of regional replication, though no single variant clearly accounted for the original GWAS signal.
28100911	1	5	theme	dental	136:141	arg1	caries					143:148	dental caries	136:148	dental caries	136:148	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	8	6	theme	replication	1396:1406	arg1	evidence					1375:1382	evidence	1375:1382	evidence of regional replication	1375:1406	Our results show evidence of regional replication, though no single variant clearly accounted for the original GWAS signal.
28100911	0	7	from	Variants	0:7	arg1	chromosome					12:21	chromosome 4q21	12:26	chromosome 4q21	12:26	Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries.
28100911	9	8	theme	additional	1603:1612	arg1	work					1614:1617	additional work	1603:1617	additional work	1603:1617	Therefore, while we interpret our results as strengthening the hypothesis that chromosome 4q21 may impact dental caries, additional work is needed.
28100911	5	9	theme	adults	897:902	arg1	samples					834:840	individual samples	823:840	individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003)	823:957	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	5	10	theme	white	891:895	arg1	adults					897:902	white adults	891:902	white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003)	891:957	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	1	11	theme	small	222:226	arg1	glycoprotein					261:272	small integrin-binding ligand N-linked glycoprotein	222:272	small integrin-binding ligand N-linked glycoprotein	222:272	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	11	theme	small	222:226	arg1	ABCG2					193:197	ABCG2	193:197	ABCG2	193:197	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	7	12	from	adults	1305:1310	arg1	evidence					1238:1245	evidence	1238:1245	evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002)	1238:1355	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	1	13	theme	integrin-binding	228:243	arg1	glycoprotein					261:272	small integrin-binding ligand N-linked glycoprotein	222:272	small integrin-binding ligand N-linked glycoprotein	222:272	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	13	theme	integrin-binding	228:243	arg1	ABCG2					193:197	ABCG2	193:197	ABCG2	193:197	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	3	14	from	variation	612:620	arg1	locus					634:638	the 4q21 locus	625:638	the 4q21 locus	625:638	Participants were assessed for dental caries via intraoral examination and 49 tag-SNPs were genotyped capturing much of the variation in the 4q21 locus.
28100911	5	15	theme	adults	851:856	arg1	samples					834:840	individual samples	823:840	individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003)	823:957	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	6	16	theme	adult	987:991	arg1	samples					993:999	black adult samples	981:999	black adult samples	981:999	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	5	17	dep	adults	851:856	arg1	rs17013735					859:868	rs17013735	859:868	rs17013735	859:868	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	7	18	theme	interaction	1276:1286	arg1	effects					1288:1294	gene-by-fluoride exposure interaction effects	1250:1294	gene-by-fluoride exposure interaction effects in white adults	1250:1310	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	5	19	theme	black	845:849	arg1	adults					851:856	black adults	845:856	black adults (rs17013735, P-value=0.0009)	845:885	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	7	20	theme	exposure	1267:1274	arg1	effects					1288:1294	gene-by-fluoride exposure interaction effects	1250:1294	gene-by-fluoride exposure interaction effects in white adults	1250:1310	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	7	21	theme	white	1299:1303	arg1	adults					1305:1310	white adults	1299:1310	white adults	1299:1310	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	2	22	theme	13	415:416	arg1	age-					418:421	age-	418:421	age-	418:421	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	4	23	used	used	660:663	arg2	models					648:653	Linear models	641:653	Linear models	641:653	Linear models were used to test for genetic association, while adjusting for sex, age and components of ancestry.
28100911	6	24	theme	non-African	1097:1107	arg1	populations					1109:1119	non-African populations	1097:1119	non-African populations	1097:1119	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	8	25	theme	GWAS	1469:1472	arg1	signal					1474:1479	the original GWAS signal	1456:1479	the original GWAS signal	1456:1479	Our results show evidence of regional replication, though no single variant clearly accounted for the original GWAS signal.
28100911	5	26	theme	association	808:818	arg1	evidence					796:803	significant evidence	784:803	significant evidence of association	784:818	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	6	27	theme	race	1146:1149	arg1	specificity					1151:1161	the race specificity	1142:1161	the race specificity of the effect	1142:1175	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	1	28	theme	ligand	245:250	arg1	glycoprotein					261:272	small integrin-binding ligand N-linked glycoprotein	222:272	small integrin-binding ligand N-linked glycoprotein	222:272	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	28	theme	ligand	245:250	arg1	ABCG2					193:197	ABCG2	193:197	ABCG2	193:197	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	3	29	theme	intraoral	537:545	arg1	examination					547:557	intraoral examination	537:557	intraoral examination	537:557	Participants were assessed for dental caries via intraoral examination and 49 tag-SNPs were genotyped capturing much of the variation in the 4q21 locus.
28100911	6	30	from	frequency	1084:1092	arg1	populations					1109:1119	non-African populations	1097:1119	non-African populations	1097:1119	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	1	31	theme	chromosomal	164:174	arg1	region					176:181	the chromosomal region 4q21	160:186	the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	160:285	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	32	theme	N-linked	252:259	arg1	glycoprotein					261:272	small integrin-binding ligand N-linked glycoprotein	222:272	small integrin-binding ligand N-linked glycoprotein	222:272	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	32	theme	N-linked	252:259	arg1	ABCG2					193:197	ABCG2	193:197	ABCG2	193:197	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	3	33	theme	dental	519:524	arg1	caries					526:531	dental caries	519:531	dental caries	519:531	Participants were assessed for dental caries via intraoral examination and 49 tag-SNPs were genotyped capturing much of the variation in the 4q21 locus.
28100911	2	34	theme	polymorphism	389:400	arg1	approach					403:410	a tag-SNP (single-nucleotide polymorphism) approach	360:410	a tag-SNP (single-nucleotide polymorphism) approach	360:410	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	7	35	from	effects	1288:1294	arg1	adults					1305:1310	white adults	1299:1310	white adults	1299:1310	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	3	36	theme	variation	612:620	arg1	much					600:603	much	600:603	much	600:603	Participants were assessed for dental caries via intraoral examination and 49 tag-SNPs were genotyped capturing much of the variation in the 4q21 locus.
28100911	1	37	theme	recent	88:93	arg1	study					119:123	A recent genome-wide association study	86:123	A recent genome-wide association study (GWAS) for dental caries	86:148	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	37	theme	recent	88:93	arg1	GWAS					126:129	GWAS	126:129	GWAS	126:129	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	2	38	theme	single-nucleotide	371:387	arg1	approach					403:410	a tag-SNP (single-nucleotide polymorphism) approach	360:410	a tag-SNP (single-nucleotide polymorphism) approach	360:410	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	7	39	theme	race-specific	1193:1205	arg1	associations					1207:1218	race-specific associations	1193:1218	race-specific associations	1193:1218	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	5	40	dep	adults	897:902	arg1	rs11938025					905:914	rs11938025	905:914	rs11938025	905:914	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	7	41	theme	effects	1288:1294	arg1	evidence					1238:1245	evidence	1238:1245	evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002)	1238:1355	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	6	42	theme	black	981:985	arg1	samples					993:999	black adult samples	981:999	black adult samples	981:999	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	2	43	theme	race-stratified	427:441	arg1	samples					443:449	13 age- and race-stratified samples	415:449	13 age- and race-stratified samples from 6 independent studies (N=4089)	415:485	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	1	44	theme	gene	275:278	arg1	family					280:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	2	45	from	studies	470:476	arg1	samples					443:449	13 age- and race-stratified samples	415:449	13 age- and race-stratified samples from 6 independent studies (N=4089)	415:485	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	5	46	theme	significant	784:794	arg1	evidence					796:803	significant evidence	784:803	significant evidence of association	784:818	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	2	47	theme	tag-SNP	362:368	arg1	approach					403:410	a tag-SNP (single-nucleotide polymorphism) approach	360:410	a tag-SNP (single-nucleotide polymorphism) approach	360:410	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	6	48	with	association	1019:1029	arg1	P-value=0.003					1048:1060	P-value=0.003	1048:1060	P-value=0.003	1048:1060	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	6	48	with	association	1019:1029	arg1	rs17013735					1036:1045	rs17013735	1036:1045	rs17013735	1036:1045	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	6	49	theme	effect	1170:1175	arg1	specificity					1151:1161	the race specificity	1142:1161	the race specificity of the effect	1142:1175	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	1	50	theme	genome-wide	95:105	arg1	study					119:123	A recent genome-wide association study	86:123	A recent genome-wide association study (GWAS) for dental caries	86:148	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	50	theme	genome-wide	95:105	arg1	GWAS					126:129	GWAS	126:129	GWAS	126:129	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	2	51	theme	age-	418:421	arg1	samples					443:449	13 age- and race-stratified samples	415:449	13 age- and race-stratified samples from 6 independent studies (N=4089)	415:485	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	8	52	theme	single	1419:1424	arg1	variant					1426:1432	no single variant	1416:1432	no single variant	1416:1432	Our results show evidence of regional replication, though no single variant clearly accounted for the original GWAS signal.
28100911	1	53	theme	association	107:117	arg1	study					119:123	A recent genome-wide association study	86:123	A recent genome-wide association study (GWAS) for dental caries	86:148	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	53	theme	association	107:117	arg1	GWAS					126:129	GWAS	126:129	GWAS	126:129	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	8	54	theme	regional	1387:1394	arg1	replication					1396:1406	regional replication	1387:1406	regional replication	1387:1406	Our results show evidence of regional replication, though no single variant clearly accounted for the original GWAS signal.
28100911	7	55	theme	SNP	1316:1318	arg1	rs2725233					1320:1328	SNP rs2725233	1316:1328	SNP rs2725233 upstream of PKD2 (P=0.002)	1316:1355	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	1	56	gly	glycoprotein	261:272	arg1	glycoprotein					261:272	small integrin-binding ligand N-linked glycoprotein	222:272	small integrin-binding ligand N-linked glycoprotein	222:272	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	56	gly	glycoprotein	261:272	arg1	ABCG2					193:197	ABCG2	193:197	ABCG2	193:197	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	4	57	theme	genetic	677:683	arg1	association					685:695	genetic association	677:695	genetic association	677:695	Linear models were used to test for genetic association, while adjusting for sex, age and components of ancestry.
28100911	7	58	from	evidence	1238:1245	arg1	adults					1305:1310	white adults	1299:1310	white adults	1299:1310	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	1	59	theme	PKD2	200:203	arg1	family					280:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	1	60	theme	ABCG2	193:197	arg1	family					280:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family	193:285	A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family.
28100911	4	61	theme	ancestry	745:752	arg1	sex					718:720	sex	718:720	sex	718:720	Linear models were used to test for genetic association, while adjusting for sex, age and components of ancestry.
28100911	4	61	theme	ancestry	745:752	arg1	components					731:740	components	731:740	components of ancestry	731:752	Linear models were used to test for genetic association, while adjusting for sex, age and components of ancestry.
28100911	4	61	theme	ancestry	745:752	arg1	age					723:725	age	723:725	age	723:725	Linear models were used to test for genetic association, while adjusting for sex, age and components of ancestry.
28100911	7	62	theme	gene-by-fluoride	1250:1265	arg1	effects					1288:1294	gene-by-fluoride exposure interaction effects	1250:1294	gene-by-fluoride exposure interaction effects in white adults	1250:1310	In addition to race-specific associations, we also observed evidence of gene-by-fluoride exposure interaction effects in white adults for SNP rs2725233 upstream of PKD2 (P=0.002).
28100911	5	63	theme	individual	823:832	arg1	samples					834:840	individual samples	823:840	individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003)	823:957	SNPs in and near PKD2 showed significant evidence of association in individual samples of black adults (rs17013735, P-value=0.0009) and white adults (rs11938025; P-value=0.0005; rs2725270, P-value=0.003).
28100911	2	64	theme	independent	458:468	arg1	N=4089					479:484	N=4089	479:484	N=4089	479:484	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	2	64	theme	independent	458:468	arg1	studies					470:476	6 independent studies	456:476	6 independent studies (N=4089)	456:485	In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089).
28100911	6	65	theme	low	1080:1082	arg1	frequency					1084:1092	low frequency	1080:1092	low frequency in non-African populations	1080:1119	Meta-analyses across black adult samples recapitulated the association with rs17013735 (P-value=0.003), which occurs at low frequency in non-African populations, possibly explaining the race specificity of the effect.
28100911	9	66	theme	dental	1588:1593	arg1	caries					1595:1600	dental caries	1588:1600	dental caries	1588:1600	Therefore, while we interpret our results as strengthening the hypothesis that chromosome 4q21 may impact dental caries, additional work is needed.
28100911	4	67	theme	Linear	641:646	arg1	models					648:653	Linear models	641:653	Linear models	641:653	Linear models were used to test for genetic association, while adjusting for sex, age and components of ancestry.
27761878	6	0	theme	BHK21	1009:1013	arg1	cells					1015:1019	parental BHK21 cells	1000:1019	parental BHK21 cells	1000:1019	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	8	1	theme	increasing	1501:1510	arg1	activation					1512:1521	increasing activation	1501:1521	increasing activation	1501:1521	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	1	2	contain	has	115:117	arg1	reticulum					100:108	The endoplasmic reticulum	84:108	The endoplasmic reticulum (ER)	84:113	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	1	2	contain	has	115:117	arg2	ability					123:129	the ability	119:129	the ability to signal organelle dysfunction	119:161	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	1	2	contain	has	115:117	arg1	ER					111:112	ER	111:112	ER	111:112	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	3	3	theme	oligosaccharyltransferase	490:514	arg1	complex					522:528	the oligosaccharyltransferase (OST) complex	486:528	the oligosaccharyltransferase (OST) complex	486:528	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	11	4	theme	moderate	1927:1934	arg1	doses					1951:1955	moderate, but not high, doses	1927:1955	moderate, but not high, doses of Tm	1927:1961	Inhibition of either PERK or p38 was sufficient to reduce cell death and apoptosis induced by moderate, but not high, doses of Tm.
27761878	6	5	theme	Tm	1074:1075	arg1	20-40 nM					1032:1039	20-40 nM	1032:1039	20-40 nM	1032:1039	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	6	5	theme	Tm	1074:1075	arg1	200-1000 nM					1058:1068	200-1000 nM	1058:1068	200-1000 nM	1058:1068	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	10	6	dep	mediators	1722:1730	arg1	p38					1733:1735	p38	1733:1735	p38	1733:1735	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	10	6	dep	mediators	1722:1730	arg1	Erk1/2					1744:1749	Erk1/2	1744:1749	Erk1/2	1744:1749	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	10	6	dep	mediators	1722:1730	arg1	Jnk1					1738:1741	Jnk1	1738:1741	Jnk1	1738:1741	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	11	7	theme	PERK	1854:1857	arg1	Inhibition					1833:1842	Inhibition	1833:1842	Inhibition of either PERK or p38	1833:1864	Inhibition of either PERK or p38 was sufficient to reduce cell death and apoptosis induced by moderate, but not high, doses of Tm.
27761878	7	8	theme	higher	1355:1360	arg1	doses					1362:1366	moderate but not higher doses	1338:1366	moderate but not higher doses of Tm	1338:1372	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	2	9	theme	severe	354:359	arg1	stress					364:369	severe ER stress	354:369	severe ER stress	354:369	In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress.
27761878	14	10	theme	stress	2156:2161	arg1	doses					2144:2148	moderate doses	2135:2148	moderate doses of ER stress	2135:2161	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	3	11	theme	complex	522:528	arg1	subunit					475:481	the Dad1 subunit	466:481	the Dad1 subunit of the oligosaccharyltransferase (OST) complex	466:528	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	5	12	theme	inositol-requiring	811:828	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	12	theme	inositol-requiring	811:828	arg1	IRE1					840:843	inositol-requiring enzyme 1 (IRE1)	811:844	inositol-requiring enzyme 1 (IRE1)	811:844	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	11	13	theme	high	1945:1948	arg1	doses					1951:1955	moderate, but not high, doses	1927:1955	moderate, but not high, doses of Tm	1927:1961	Inhibition of either PERK or p38 was sufficient to reduce cell death and apoptosis induced by moderate, but not high, doses of Tm.
27761878	4	14	theme	stress	642:647	arg1	signaling					649:657	ER stress signaling	639:657	ER stress signaling	639:657	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	1	15	theme	signaling	177:185	arg1	network					187:193	a complex signaling network	167:193	a complex signaling network known as the unfolded protein response (UPR)	167:238	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	9	16	theme	extracellular	1569:1581	arg1	kinases					1593:1599	the extracellular regulated kinases	1565:1599	the extracellular regulated kinases (Erk1/2)	1565:1608	Interestingly, Tm induced the extracellular regulated kinases (Erk1/2) only at moderate doses of Tm.
27761878	9	16	theme	extracellular	1569:1581	arg1	Erk1/2					1602:1607	Erk1/2	1602:1607	Erk1/2	1602:1607	Interestingly, Tm induced the extracellular regulated kinases (Erk1/2) only at moderate doses of Tm.
27761878	10	17	theme	transmembrane	1657:1669	arg1	sensors					1678:1684	ER transmembrane stress sensors	1654:1684	ER transmembrane stress sensors (IRE1, PERK)	1654:1697	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	6	18	theme	high	1046:1049	arg1	doses					1051:1055	moderate (20-40 nM) and high doses	1022:1055	doses	1051:1055	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	5	19	theme	TS	983:984	arg1	treatment					986:994	TS treatment	983:994	TS treatment	983:994	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	2	20	theme	fibroblast	263:272	arg1	cells					274:278	hamster fibroblast cells	255:278	hamster fibroblast cells exhibiting moderate levels of ER stress	255:318	In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress.
27761878	5	21	theme	stress	783:788	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	21	theme	stress	783:788	arg1	IRE1					840:843	inositol-requiring enzyme 1 (IRE1)	811:844	inositol-requiring enzyme 1 (IRE1)	811:844	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	21	theme	stress	783:788	arg1	PERK					908:911	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	4	22	theme	weak	620:623	arg1	activation					625:634	weak activation	620:634	weak activation of ER stress signaling	620:657	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	7	23	with	activity	1208:1215	arg1	XeC					1278:1280	XeC	1278:1280	XeC	1278:1280	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	7	23	with	activity	1208:1215	arg1	2-APB					1252:1256	2-APB	1252:1256	2-APB	1252:1256	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	7	23	with	activity	1208:1215	arg1	borate					1244:1249	2-aminoethoxydiphenyl borate	1222:1249	2-aminoethoxydiphenyl borate (2-APB)	1222:1257	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	7	23	with	activity	1208:1215	arg1	C					1275:1275	Xestospongin C	1262:1275	Xestospongin C (XeC)	1262:1281	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	10	24	theme	sensors	1678:1684	arg1	Inhibition					1640:1649	Inhibition	1640:1649	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2)	1640:1750	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	5	25	theme	mediators	800:808	arg1	analysis					764:771	A dose-response analysis	748:771	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK),	748:913	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	14	26	from	doses	2234:2238	arg1	distinct					2213:2220	distinct	2213:2220	distinct	2213:2220	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	10	27	theme	ER	1822:1823	arg1	stress					1825:1830	ER stress	1822:1830	ER stress	1822:1830	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	5	28	theme	activation	951:960	arg1	intensity					962:970	activation intensity	951:970	activation intensity similar to TS treatment	951:994	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	3	29	link	N-linked	386:393	arg1	glycosylation					395:407	N-linked glycosylation	386:407	N-linked glycosylation	386:407	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	5	30	theme	similar	972:978	arg1	intensity					962:970	activation intensity	951:970	activation intensity similar to TS treatment	951:994	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	9	31	theme	moderate	1618:1625	arg1	doses					1627:1631	moderate doses	1618:1631	moderate doses of Tm	1618:1637	Interestingly, Tm induced the extracellular regulated kinases (Erk1/2) only at moderate doses of Tm.
27761878	0	32	theme	p38-dependent	59:71	arg1	apoptosis					73:81	p38-dependent apoptosis	59:81	p38-dependent apoptosis	59:81	Moderate endoplasmic reticulum stress activates a PERK and p38-dependent apoptosis.
27761878	5	33	theme	key	776:778	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	33	theme	key	776:778	arg1	IRE1					840:843	inositol-requiring enzyme 1 (IRE1)	811:844	inositol-requiring enzyme 1 (IRE1)	811:844	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	33	theme	key	776:778	arg1	PERK					908:911	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	1	34	theme	signal	134:139	arg1	dysfunction					151:161	signal organelle dysfunction	134:161	signal organelle dysfunction	134:161	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	8	35	theme	kinase	1387:1392	arg1	activation					1394:1403	kinase activation	1387:1403	kinase activation over a range of Tm exposures	1387:1432	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	4	36	theme	stress	718:723	arg1	500-1000 nM					734:744	500-1000 nM	734:744	500-1000 nM	734:744	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	4	36	theme	stress	718:723	arg1	studies					725:731	ER stress studies	715:731	ER stress studies (500-1000 nM)	715:745	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	5	37	theme	kinase	900:905	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	37	theme	kinase	900:905	arg1	PERK					908:911	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	12	38	theme	survivin	2042:2049	arg1	proteins					2051:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	During ER stress, cells exhibited a rapid decline in anti-apoptotic Mcl-1 and survivin proteins.
27761878	10	39	used	used	1756:1759	arg2	Inhibition					1640:1649	Inhibition	1640:1649	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2)	1640:1750	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	12	40	theme	rapid	2000:2004	arg1	decline					2006:2012	a rapid decline	1998:2012	a rapid decline in anti-apoptotic Mcl-1 and survivin proteins	1998:2058	During ER stress, cells exhibited a rapid decline in anti-apoptotic Mcl-1 and survivin proteins.
27761878	14	41	theme	apoptosis	2249:2257	arg1	activation					2259:2268	apoptosis activation	2249:2268	apoptosis activation at moderate levels of stress	2249:2297	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	3	42	theme	glycosylation	395:407	arg1	Inhibition					372:381	Inhibition	372:381	Inhibition of N-linked glycosylation	372:407	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	0	43	theme	Moderate	0:7	arg1	reticulum					21:29	Moderate endoplasmic reticulum	0:29	Moderate endoplasmic reticulum stress	0:36	Moderate endoplasmic reticulum stress activates a PERK and p38-dependent apoptosis.
27761878	7	44	theme	2-aminoethoxydiphenyl	1222:1242	arg1	2-APB					1252:1256	2-APB	1252:1256	2-APB	1252:1256	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	7	44	theme	2-aminoethoxydiphenyl	1222:1242	arg1	borate					1244:1249	2-aminoethoxydiphenyl borate	1222:1249	2-aminoethoxydiphenyl borate (2-APB)	1222:1257	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	11	45	theme	Tm	1960:1961	arg1	doses					1951:1955	moderate, but not high, doses	1927:1955	moderate, but not high, doses of Tm	1927:1961	Inhibition of either PERK or p38 was sufficient to reduce cell death and apoptosis induced by moderate, but not high, doses of Tm.
27761878	8	46	theme	Tm	1421:1422	arg1	exposures					1424:1432	Tm exposures	1421:1432	Tm exposures	1421:1432	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	0	47	theme	reticulum	21:29	arg1	stress					31:36	Moderate endoplasmic reticulum stress	0:36	Moderate endoplasmic reticulum stress	0:36	Moderate endoplasmic reticulum stress activates a PERK and p38-dependent apoptosis.
27761878	5	48	theme	endoplasmic	878:888	arg1	reticulum					890:898	protein kinase R (PKR)-like endoplasmic reticulum	850:898	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	3	49	with	inhibition	543:552	arg1	Tm					572:573	Tm	572:573	Tm	572:573	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	3	49	with	inhibition	543:552	arg1	tunicamycin					559:569	tunicamycin	559:569	tunicamycin (Tm)	559:574	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	5	50	theme	Tm	936:937	arg1	20-40 nM					924:931	20-40 nM	924:931	20-40 nM of Tm to generate activation intensity similar to TS treatment	924:994	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	8	51	theme	p38	1447:1449	arg1	SAPK					1484:1487	SAPK	1484:1487	SAPK	1484:1487	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	8	51	theme	p38	1447:1449	arg1	kinase					1476:1481	p38 stress-activated protein kinase	1447:1481	the p38 stress-activated protein kinase (SAPK)	1443:1488	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	14	52	theme	higher	2227:2232	arg1	doses					2234:2238	higher doses	2227:2238	higher doses	2227:2238	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	2	53	theme	stress	313:318	arg1	levels					300:305	moderate levels	291:305	moderate levels of ER stress	291:318	In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress.
27761878	15	54	theme	dose-dependent	2493:2506	arg1	manner					2508:2513	a dose-dependent manner	2491:2513	a dose-dependent manner	2491:2513	Studies exploring ER stress signaling should recognize that this signaling acts as a rheostat rather than a simple switch, behaving distinctively in a dose-dependent manner.
27761878	7	55	theme	Ca2+	1186:1189	arg1	release					1191:1197	ER Ca2+ release	1183:1197	ER Ca2+ release	1183:1197	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	8	56	theme	protein	1468:1474	arg1	SAPK					1484:1487	SAPK	1484:1487	SAPK	1484:1487	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	8	56	theme	protein	1468:1474	arg1	kinase					1476:1481	p38 stress-activated protein kinase	1447:1481	the p38 stress-activated protein kinase (SAPK)	1443:1488	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	8	57	theme	Tm	1528:1529	arg1	dosage					1531:1536	Tm dosage	1528:1536	Tm dosage	1528:1536	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	1	58	theme	unfolded	208:215	arg1	response					225:232	the unfolded protein response	204:232	the unfolded protein response (UPR)	204:238	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	1	58	theme	unfolded	208:215	arg1	UPR					235:237	UPR	235:237	UPR	235:237	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	4	59	theme	Temperature	577:587	arg1	shift					589:593	Temperature shift	577:593	Temperature shift (TS) treatment	577:608	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	4	59	theme	Temperature	577:587	arg1	TS					596:597	TS	596:597	TS	596:597	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	12	60	theme	ER	1971:1972	arg1	stress					1974:1979	ER stress	1971:1979	ER stress	1971:1979	During ER stress, cells exhibited a rapid decline in anti-apoptotic Mcl-1 and survivin proteins.
27761878	7	61	theme	Tm	1371:1372	arg1	doses					1362:1366	moderate but not higher doses	1338:1366	moderate but not higher doses of Tm	1338:1372	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	14	62	theme	stress	2187:2192	arg1	signaling					2194:2202	stress signaling	2187:2202	stress signaling	2187:2202	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	15	63	theme	ER	2360:2361	arg1	signaling					2370:2378	ER stress signaling	2360:2378	ER stress signaling	2360:2378	Studies exploring ER stress signaling should recognize that this signaling acts as a rheostat rather than a simple switch, behaving distinctively in a dose-dependent manner.
27761878	14	64	theme	moderate	2273:2280	arg1	levels					2282:2287	moderate levels	2273:2287	moderate levels of stress	2273:2297	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	6	65	theme	parental	1000:1007	arg1	cells					1015:1019	parental BHK21 cells	1000:1019	parental BHK21 cells	1000:1019	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	2	66	theme	hamster	255:261	arg1	cells					274:278	hamster fibroblast cells	255:278	hamster fibroblast cells exhibiting moderate levels of ER stress	255:318	In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress.
27761878	10	67	theme	ER	1654:1655	arg1	sensors					1678:1684	ER transmembrane stress sensors	1654:1684	ER transmembrane stress sensors (IRE1, PERK)	1654:1697	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	5	68	theme	enzyme	830:835	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	68	theme	enzyme	830:835	arg1	IRE1					840:843	inositol-requiring enzyme 1 (IRE1)	811:844	inositol-requiring enzyme 1 (IRE1)	811:844	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	7	69	theme	moderate	1338:1345	arg1	doses					1362:1366	moderate but not higher doses	1338:1366	moderate but not higher doses of Tm	1338:1372	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	6	70	theme	stress	1152:1157	arg1	response					1159:1166	stress response	1152:1166	stress response	1152:1166	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	14	71	theme	ER	2153:2154	arg1	stress					2156:2161	ER stress	2153:2161	ER stress	2153:2161	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	2	72	theme	moderate	291:298	arg1	levels					300:305	moderate levels	291:305	moderate levels of ER stress	291:318	In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress.
27761878	1	73	theme	complex	169:175	arg1	network					187:193	a complex signaling network	167:193	a complex signaling network known as the unfolded protein response (UPR)	167:238	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	4	74	theme	ER	639:640	arg1	signaling					649:657	ER stress signaling	639:657	ER stress signaling	639:657	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	10	75	theme	apoptosis	1794:1802	arg1	activation					1804:1813	apoptosis activation	1794:1813	apoptosis activation during ER stress	1794:1830	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	3	76	theme	direct	536:541	arg1	inhibition					543:552	direct inhibition	536:552	direct inhibition with tunicamycin (Tm)	536:574	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	12	77	from	decline	2006:2012	arg1	proteins					2051:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	During ER stress, cells exhibited a rapid decline in anti-apoptotic Mcl-1 and survivin proteins.
27761878	5	78	theme	ER	780:781	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	78	theme	ER	780:781	arg1	IRE1					840:843	inositol-requiring enzyme 1 (IRE1)	811:844	inositol-requiring enzyme 1 (IRE1)	811:844	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	78	theme	ER	780:781	arg1	PERK					908:911	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	9	79	theme	regulated	1583:1591	arg1	kinases					1593:1599	the extracellular regulated kinases	1565:1599	the extracellular regulated kinases (Erk1/2)	1565:1608	Interestingly, Tm induced the extracellular regulated kinases (Erk1/2) only at moderate doses of Tm.
27761878	9	79	theme	regulated	1583:1591	arg1	Erk1/2					1602:1607	Erk1/2	1602:1607	Erk1/2	1602:1607	Interestingly, Tm induced the extracellular regulated kinases (Erk1/2) only at moderate doses of Tm.
27761878	5	80	theme	signaling	790:798	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	80	theme	signaling	790:798	arg1	IRE1					840:843	inositol-requiring enzyme 1 (IRE1)	811:844	inositol-requiring enzyme 1 (IRE1)	811:844	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	80	theme	signaling	790:798	arg1	PERK					908:911	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	6	81	theme	signaling-based	1121:1135	arg1	differences					1137:1147	physiological and signaling-based differences	1103:1147	physiological and signaling-based differences in stress response	1103:1166	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	10	82	dep	sensors	1678:1684	arg1	PERK					1693:1696	PERK	1693:1696	PERK	1693:1696	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	10	82	dep	sensors	1678:1684	arg1	IRE1					1687:1690	IRE1	1687:1690	IRE1	1687:1690	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	10	83	theme	stress	1671:1676	arg1	sensors					1678:1684	ER transmembrane stress sensors	1654:1684	ER transmembrane stress sensors (IRE1, PERK)	1654:1697	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	13	84	theme	PERK	2075:2078	arg1	Inhibition					2061:2070	Inhibition	2061:2070	Inhibition of PERK	2061:2078	Inhibition of PERK was sufficient to block this affect.
27761878	10	85	theme	signaling	1712:1720	arg1	mediators					1722:1730	cytosolic signaling mediators	1702:1730	cytosolic signaling mediators (p38, Jnk1, Erk1/2)	1702:1750	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	6	86	theme	physiological	1103:1115	arg1	differences					1137:1147	physiological and signaling-based differences	1103:1147	physiological and signaling-based differences in stress response	1103:1166	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	14	87	theme	moderate	2135:2142	arg1	doses					2144:2148	moderate doses	2135:2148	moderate doses of ER stress	2135:2161	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	7	88	theme	Xestospongin	1262:1273	arg1	XeC					1278:1280	XeC	1278:1280	XeC	1278:1280	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	7	88	theme	Xestospongin	1262:1273	arg1	C					1275:1275	Xestospongin C	1262:1275	Xestospongin C (XeC)	1262:1281	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	4	89	theme	Tm	685:686	arg1	doses					676:680	doses	676:680	doses of Tm that are typically used in ER stress studies (500-1000 nM)	676:745	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	6	90	from	differences	1137:1147	arg1	response					1159:1166	stress response	1152:1166	stress response	1152:1166	In parental BHK21 cells, moderate (20-40 nM) and high doses (200-1000 nM) of Tm were compared to identify physiological and signaling-based differences in stress response.
27761878	11	91	theme	cell	1891:1894	arg1	death					1896:1900	cell death	1891:1900	cell death	1891:1900	Inhibition of either PERK or p38 was sufficient to reduce cell death and apoptosis induced by moderate, but not high, doses of Tm.
27761878	4	92	theme	signaling	649:657	arg1	activation					625:634	weak activation	620:634	weak activation of ER stress signaling	620:657	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	1	93	theme	organelle	141:149	arg1	dysfunction					151:161	signal organelle dysfunction	134:161	signal organelle dysfunction	134:161	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	9	94	theme	Tm	1636:1637	arg1	doses					1627:1631	moderate doses	1618:1631	moderate doses of Tm	1618:1637	Interestingly, Tm induced the extracellular regulated kinases (Erk1/2) only at moderate doses of Tm.
27761878	8	95	theme	activation	1394:1403	arg1	Analysis					1375:1382	Analysis	1375:1382	Analysis of kinase activation over a range of Tm exposures	1375:1432	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	14	96	from	levels	2282:2287	arg1	activation					2259:2268	apoptosis activation	2249:2268	apoptosis activation at moderate levels of stress	2249:2297	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	15	97	theme	simple	2450:2455	arg1	signaling					2407:2415	this signaling	2402:2415	this signaling	2402:2415	Studies exploring ER stress signaling should recognize that this signaling acts as a rheostat rather than a simple switch, behaving distinctively in a dose-dependent manner.
27761878	15	97	theme	simple	2450:2455	arg1	switch					2457:2462	a simple switch	2448:2462	a simple switch	2448:2462	Studies exploring ER stress signaling should recognize that this signaling acts as a rheostat rather than a simple switch, behaving distinctively in a dose-dependent manner.
27761878	5	98	theme	reticulum	890:898	arg1	mediators					800:808	key ER stress signaling mediators	776:808	key ER stress signaling mediators	776:808	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	5	98	theme	reticulum	890:898	arg1	PERK					908:911	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	11	99	theme	p38	1862:1864	arg1	Inhibition					1833:1842	Inhibition	1833:1842	Inhibition of either PERK or p38	1833:1864	Inhibition of either PERK or p38 was sufficient to reduce cell death and apoptosis induced by moderate, but not high, doses of Tm.
27761878	12	100	theme	Mcl-1	2032:2036	arg1	proteins					2051:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	During ER stress, cells exhibited a rapid decline in anti-apoptotic Mcl-1 and survivin proteins.
27761878	12	101	theme	anti-apoptotic	2017:2030	arg1	proteins					2051:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	anti-apoptotic Mcl-1 and survivin proteins	2017:2058	During ER stress, cells exhibited a rapid decline in anti-apoptotic Mcl-1 and survivin proteins.
27761878	4	102	theme	ER	715:716	arg1	500-1000 nM					734:744	500-1000 nM	734:744	500-1000 nM	734:744	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	4	102	theme	ER	715:716	arg1	studies					725:731	ER stress studies	715:731	ER stress studies (500-1000 nM)	715:745	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	2	103	theme	ER	361:362	arg1	stress					364:369	severe ER stress	354:369	severe ER stress	354:369	In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress.
27761878	5	104	theme	dose-response	750:762	arg1	analysis					764:771	A dose-response analysis	748:771	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK),	748:913	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	1	105	theme	endoplasmic	88:98	arg1	reticulum					100:108	The endoplasmic reticulum	84:108	The endoplasmic reticulum (ER)	84:113	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	1	105	theme	endoplasmic	88:98	arg1	ER					111:112	ER	111:112	ER	111:112	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	8	106	theme	exposures	1424:1432	arg1	range					1412:1416	a range	1410:1416	a range of Tm exposures	1410:1432	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	5	107	theme	-like	872:876	arg1	reticulum					890:898	protein kinase R (PKR)-like endoplasmic reticulum	850:898	protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)	850:912	A dose-response analysis of key ER stress signaling mediators, inositol-requiring enzyme 1 (IRE1) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), revealed 20-40 nM of Tm to generate activation intensity similar to TS treatment.
27761878	7	108	theme	ITPR	1203:1206	arg1	activity					1208:1215	ITPR activity	1203:1215	ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC)	1203:1281	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	10	109	theme	mediators	1722:1730	arg1	Inhibition					1640:1649	Inhibition	1640:1649	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2)	1640:1750	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	14	110	theme	p38	2327:2329	arg1	signaling					2331:2339	p38 signaling	2327:2339	p38 signaling	2327:2339	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	7	111	theme	release	1191:1197	arg1	Inhibition					1169:1178	Inhibition	1169:1178	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC)	1169:1281	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	3	112	theme	N-linked	386:393	arg1	glycosylation					395:407	N-linked glycosylation	386:407	N-linked glycosylation	386:407	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	8	113	theme	stress-activated	1451:1466	arg1	SAPK					1484:1487	SAPK	1484:1487	SAPK	1484:1487	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	8	113	theme	stress-activated	1451:1466	arg1	kinase					1476:1481	p38 stress-activated protein kinase	1447:1481	the p38 stress-activated protein kinase (SAPK)	1443:1488	Analysis of kinase activation over a range of Tm exposures revealed the p38 stress-activated protein kinase (SAPK) to display increasing activation with Tm dosage.
27761878	10	114	theme	cytosolic	1702:1710	arg1	mediators					1722:1730	cytosolic signaling mediators	1702:1730	cytosolic signaling mediators (p38, Jnk1, Erk1/2)	1702:1750	Inhibition of ER transmembrane stress sensors (IRE1, PERK) or cytosolic signaling mediators (p38, Jnk1, Erk1/2) was used to evaluate pathways involved in apoptosis activation during ER stress.
27761878	3	115	theme	temperature-sensitive	432:452	arg1	mutation					454:461	a temperature-sensitive mutation	430:461	a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex	430:528	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	7	116	theme	ER	1183:1184	arg1	release					1191:1197	ER Ca2+ release	1183:1197	ER Ca2+ release	1183:1197	Inhibition of ER Ca2+ release via ITPR activity with 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) was sufficient to protect against apoptosis induced by moderate but not higher doses of Tm.
27761878	3	117	from	mutation	454:461	arg1	subunit					475:481	the Dad1 subunit	466:481	the Dad1 subunit of the oligosaccharyltransferase (OST) complex	466:528	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	2	118	theme	ER	310:311	arg1	stress					313:318	ER stress	310:318	ER stress	310:318	In this work, hamster fibroblast cells exhibiting moderate levels of ER stress were compared to those exhibiting severe ER stress.
27761878	4	119	theme	shift	589:593	arg1	treatment					600:608	Temperature shift (TS) treatment	577:608	Temperature shift (TS) treatment	577:608	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
27761878	3	120	theme	Dad1	470:473	arg1	subunit					475:481	the Dad1 subunit	466:481	the Dad1 subunit of the oligosaccharyltransferase (OST) complex	466:528	Inhibition of N-linked glycosylation was accomplished via a temperature-sensitive mutation in the Dad1 subunit of the oligosaccharyltransferase (OST) complex or by direct inhibition with tunicamycin (Tm).
27761878	15	121	theme	stress	2363:2368	arg1	signaling					2370:2378	ER stress signaling	2360:2378	ER stress signaling	2360:2378	Studies exploring ER stress signaling should recognize that this signaling acts as a rheostat rather than a simple switch, behaving distinctively in a dose-dependent manner.
27761878	1	122	theme	protein	217:223	arg1	response					225:232	the unfolded protein response	204:232	the unfolded protein response (UPR)	204:238	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	1	122	theme	protein	217:223	arg1	UPR					235:237	UPR	235:237	UPR	235:237	The endoplasmic reticulum (ER) has the ability to signal organelle dysfunction via a complex signaling network known as the unfolded protein response (UPR).
27761878	14	123	theme	stress	2292:2297	arg1	levels					2282:2287	moderate levels	2273:2287	moderate levels of stress	2273:2297	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	14	124	theme	signaling	2194:2202	arg1	patterns					2175:2182	patterns	2175:2182	patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling	2175:2339	This work reveals moderate doses of ER stress to generate patterns of stress signaling that are distinct from higher doses and that apoptosis activation at moderate levels of stress are dependent upon PERK and p38 signaling.
27761878	0	125	theme	endoplasmic	9:19	arg1	reticulum					21:29	Moderate endoplasmic reticulum	0:29	Moderate endoplasmic reticulum stress	0:36	Moderate endoplasmic reticulum stress activates a PERK and p38-dependent apoptosis.
27761878	4	126	used	used	707:710	arg2	Tm					685:686	Tm	685:686	Tm that are typically used in ER stress studies (500-1000 nM)	685:745	Temperature shift (TS) treatment generated weak activation of ER stress signaling when compared to doses of Tm that are typically used in ER stress studies (500-1000 nM).
32986846	11	0	theme	AD	1794:1795	arg1	development					1779:1789	the development	1775:1789	the development of AD	1775:1795	Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.
32986846	0	1	from	profile	13:19	arg1	hippocampus					35:45	hippocampus	35:45	hippocampus	35:45	The N-glycan profile in cortex and hippocampus is altered in Alzheimer disease.
32986846	0	1	from	profile	13:19	arg1	cortex					24:29	cortex	24:29	cortex	24:29	The N-glycan profile in cortex and hippocampus is altered in Alzheimer disease.
32986846	10	2	contain	contained	1545:1553	arg1	glycan					1431:1436	One glycan	1427:1436	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control	1427:1543	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	2	contain	contained	1545:1553	arg2	galactose					1636:1644	a terminal galactose	1625:1644	a terminal galactose decorated with fucose and sialic acid	1625:1682	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	2	contain	contained	1545:1553	arg2	epitope					1599:1605	a structurally and functionally interesting epitope	1555:1605	a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid	1555:1682	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	5	3	gly	glycoproteins	837:849	arg1	glycoproteins					837:849	brain glycoproteins	831:849	brain glycoproteins	831:849	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	2	4	theme	glycans	313:319	arg1	roles					304:308	the roles	300:308	the roles of glycans in the development of AD	300:344	Still, the roles of glycans in the development of AD are relatively unexplored.
32986846	0	5	theme	Alzheimer	61:69	arg1	disease					71:77	Alzheimer disease	61:77	Alzheimer disease	61:77	The N-glycan profile in cortex and hippocampus is altered in Alzheimer disease.
32986846	7	6	from	levels	1106:1111	arg1	AD					1116:1117	AD	1116:1117	AD	1116:1117	Two glycans in cortex and four in hippocampus showed different levels in AD compared to control brain.
32986846	3	7	from	pattern	464:470	arg1	patients					475:482	patients	475:482	patients with different stages of cognitive impairment, including AD	475:542	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	1	8	theme	brain	148:152	arg1	functions					154:162	brain functions	148:162	brain functions	148:162	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	1	8	theme	brain	148:152	arg1	processes					175:183	processes	175:183	processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation	175:290	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	4	9	with	patients	660:667	arg1	AD					674:675	AD	674:675	AD	674:675	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	6	10	theme	different	962:970	arg1	levels					972:977	significantly different levels	948:977	significantly different levels in hippocampus	948:992	Eleven glycans showed significantly different levels in hippocampus compared to cortex in both control and AD brain.
32986846	10	11	from	cortex	1512:1517	arg1	AD					1522:1523	AD	1522:1523	AD	1522:1523	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	3	12	with	patients	475:482	arg1	stages					499:504	different stages	489:504	different stages	489:504	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	3	12	with	patients	475:482	arg1	AD					541:542	AD	541:542	AD	541:542	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	8	13	theme	confirmed	1273:1281	arg1	N-acetylglucosamine					1306:1324	a confirmed or potential bisecting N-acetylglucosamine	1271:1324	a confirmed or potential bisecting N-acetylglucosamine (GlcNAc)	1271:1333	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	13	theme	confirmed	1273:1281	arg1	acid					1241:1244	one sialic acid	1230:1244	one sialic acid	1230:1244	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	13	theme	confirmed	1273:1281	arg1	GlcNAc					1327:1332	GlcNAc	1327:1332	GlcNAc	1327:1332	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	4	14	theme	asparagine-linked	694:710	arg1	consequence					580:590	a consequence	578:590	a consequence	578:590	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	4	14	theme	asparagine-linked	694:710	arg1	profile					730:736	the asparagine-linked (N-linked) glycan profile	690:736	the asparagine-linked (N-linked) glycan profile	690:736	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	2	15	from	roles	304:308	arg1	development					328:338	the development	324:338	the development of AD	324:344	Still, the roles of glycans in the development of AD are relatively unexplored.
32986846	3	16	theme	cognitive	509:517	arg1	impairment					519:528	cognitive impairment	509:528	cognitive impairment	509:528	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	4	17	link	asparagine-linked	694:710	arg1	consequence					580:590	a consequence	578:590	a consequence	578:590	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	4	17	link	asparagine-linked	694:710	arg1	profile					730:736	the asparagine-linked (N-linked) glycan profile	690:736	the asparagine-linked (N-linked) glycan profile	690:736	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	4	18	theme	control	774:780	arg1	brain					782:786	AD and control brain	767:786	brain	782:786	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	8	19	theme	sialic	1234:1239	arg1	N-acetylglucosamine					1306:1324	a confirmed or potential bisecting N-acetylglucosamine	1271:1324	a confirmed or potential bisecting N-acetylglucosamine (GlcNAc)	1271:1333	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	19	theme	sialic	1234:1239	arg1	fucose					1260:1265	at least one fucose	1247:1265	at least one fucose	1247:1265	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	19	theme	sialic	1234:1239	arg1	acid					1241:1244	one sialic acid	1230:1244	one sialic acid	1230:1244	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	3	20	theme	different	489:497	arg1	stages					499:504	different stages	489:504	different stages	489:504	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	3	20	theme	different	489:497	arg1	AD					541:542	AD	541:542	AD	541:542	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	11	21	theme	further	1810:1816	arg1	studies					1818:1824	further studies	1810:1824	further studies	1810:1824	Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.
32986846	3	22	theme	cerebrospinal	394:406	arg1	CSF					415:417	CSF	415:417	CSF	415:417	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	3	22	theme	cerebrospinal	394:406	arg1	fluid					408:412	cerebrospinal fluid	394:412	cerebrospinal fluid (CSF)	394:418	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	10	23	theme	lower	1475:1479	arg1	levels					1481:1486	significantly lower levels	1461:1486	significantly lower levels in both hippocampus and cortex in AD	1461:1523	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	8	24	contain	had	1202:1204	arg2	structures					1214:1223	similar structures	1206:1223	similar structures	1206:1223	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	24	contain	had	1202:1204	arg1	glycans					1150:1156	All glycans	1146:1156	All glycans that differed between controls and AD brain	1146:1200	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	11	25	from	component	1762:1770	arg1	development					1779:1789	the development	1775:1789	the development of AD	1775:1795	Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.
32986846	4	26	theme	N-linked	713:720	arg1	consequence					580:590	a consequence	578:590	a consequence	578:590	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	4	26	theme	N-linked	713:720	arg1	profile					730:736	the asparagine-linked (N-linked) glycan profile	690:736	the asparagine-linked (N-linked) glycan profile	690:736	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	6	27	dep	showed	941:946	arg1	compared					994:1001	compared	994:1001	showed significantly different levels in hippocampus compared to cortex in both control and AD brain	941:1040	Eleven glycans showed significantly different levels in hippocampus compared to cortex in both control and AD brain.
32986846	2	28	theme	AD	343:344	arg1	development					328:338	the development	324:338	the development of AD	324:344	Still, the roles of glycans in the development of AD are relatively unexplored.
32986846	0	29	theme	N-glycan	4:11	arg1	profile					13:19	The N-glycan profile	0:19	The N-glycan profile in cortex and hippocampus	0:45	The N-glycan profile in cortex and hippocampus is altered in Alzheimer disease.
32986846	6	30	from	levels	972:977	arg1	hippocampus					982:992	hippocampus	982:992	hippocampus	982:992	Eleven glycans showed significantly different levels in hippocampus compared to cortex in both control and AD brain.
32986846	5	31	theme	mass	896:899	arg1	LC-MS/MS					915:922	LC-MS/MS	915:922	LC-MS/MS	915:922	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	5	31	theme	mass	896:899	arg1	spectrometry					901:912	liquid chromatography-tandem mass spectrometry	867:912	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	867:923	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	6	32	theme	AD	1033:1034	arg1	brain					1036:1040	AD brain	1033:1040	AD brain	1033:1040	Eleven glycans showed significantly different levels in hippocampus compared to cortex in both control and AD brain.
32986846	7	33	theme	control	1131:1137	arg1	brain					1139:1143	control brain	1131:1143	control brain	1131:1143	Two glycans in cortex and four in hippocampus showed different levels in AD compared to control brain.
32986846	4	34	theme	patients	660:667	arg1	brain					651:655	the brain	647:655	the brain of patients with AD	647:675	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	1	35	theme	Protein	80:86	arg1	glycosylation					88:100	Protein glycosylation	80:100	Protein glycosylation	80:100	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	4	36	theme	glycan	618:623	arg1	profile					625:631	the glycan profile	614:631	the glycan profile	614:631	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	1	37	theme	synaptic	252:259	arg1	function					261:268	synaptic function	252:268	synaptic function	252:268	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	5	38	theme	chromatography-tandem	874:894	arg1	LC-MS/MS					915:922	LC-MS/MS	915:922	LC-MS/MS	915:922	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	5	38	theme	chromatography-tandem	874:894	arg1	spectrometry					901:912	liquid chromatography-tandem mass spectrometry	867:912	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	867:923	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	3	39	theme	impairment	519:528	arg1	stages					499:504	different stages	489:504	different stages	489:504	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	3	39	theme	impairment	519:528	arg1	AD					541:542	AD	541:542	AD	541:542	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	8	40	theme	bisecting	1296:1304	arg1	N-acetylglucosamine					1306:1324	a confirmed or potential bisecting N-acetylglucosamine	1271:1324	a confirmed or potential bisecting N-acetylglucosamine (GlcNAc)	1271:1333	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	40	theme	bisecting	1296:1304	arg1	acid					1241:1244	one sialic acid	1230:1244	one sialic acid	1230:1244	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	40	theme	bisecting	1296:1304	arg1	GlcNAc					1327:1332	GlcNAc	1327:1332	GlcNAc	1327:1332	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	41	theme	potential	1286:1294	arg1	N-acetylglucosamine					1306:1324	a confirmed or potential bisecting N-acetylglucosamine	1271:1324	a confirmed or potential bisecting N-acetylglucosamine (GlcNAc)	1271:1333	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	41	theme	potential	1286:1294	arg1	acid					1241:1244	one sialic acid	1230:1244	one sialic acid	1230:1244	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	8	41	theme	potential	1286:1294	arg1	GlcNAc					1327:1332	GlcNAc	1327:1332	GlcNAc	1327:1332	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	10	42	from	present	1450:1456	arg1	levels					1481:1486	significantly lower levels	1461:1486	significantly lower levels in both hippocampus and cortex in AD	1461:1523	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	43	theme	terminal	1627:1634	arg1	galactose					1636:1644	a terminal galactose	1625:1644	a terminal galactose decorated with fucose and sialic acid	1625:1682	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	43	theme	terminal	1627:1634	arg1	epitope					1599:1605	a structurally and functionally interesting epitope	1555:1605	a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid	1555:1682	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	44	theme	sialic	1672:1677	arg1	acid					1679:1682	sialic acid	1672:1682	sialic acid	1672:1682	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	8	45	theme	similar	1206:1212	arg1	structures					1214:1223	similar structures	1206:1223	similar structures	1206:1223	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	4	46	link	N-linked	713:720	arg1	consequence					580:590	a consequence	578:590	a consequence	578:590	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	4	46	link	N-linked	713:720	arg1	profile					730:736	the asparagine-linked (N-linked) glycan profile	690:736	the asparagine-linked (N-linked) glycan profile	690:736	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	9	47	theme	AD	1419:1420	arg1	CSF					1422:1424	AD CSF	1419:1424	AD CSF	1419:1424	The glycans that were altered in AD brain differed from those that were altered in AD CSF.
32986846	10	48	theme	interesting	1587:1597	arg1	galactose					1636:1644	a terminal galactose	1625:1644	a terminal galactose decorated with fucose and sialic acid	1625:1682	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	48	theme	interesting	1587:1597	arg1	epitope					1599:1605	a structurally and functionally interesting epitope	1555:1605	a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid	1555:1682	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	3	49	theme	Glycomics	373:381	arg1	studies					383:389	Glycomics studies	373:389	Glycomics studies of cerebrospinal fluid (CSF)	373:418	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	5	50	attach	liberated	816:824	arg1	glycoproteins					837:849	brain glycoproteins	831:849	brain glycoproteins	831:849	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	5	50	attach	liberated	816:824	arg2	Glycans					789:795	Glycans	789:795	Glycans	789:795	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	3	51	theme	healthy	557:563	arg1	controls					565:572	healthy controls	557:572	healthy controls	557:572	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	1	52	from	defective	194:202	arg1	AD					226:227	AD	226:227	AD	226:227	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	1	52	from	defective	194:202	arg1	disease					217:223	Alzheimer disease	207:223	Alzheimer disease (AD)	207:228	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	10	53	from	hippocampus	1496:1506	arg1	AD					1522:1523	AD	1522:1523	AD	1522:1523	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	1	54	theme	memory	275:280	arg1	formation					282:290	memory formation	275:290	memory formation	275:290	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	11	55	theme	important	1752:1760	arg1	component					1762:1770	an important component	1749:1770	an important component in the development of AD	1749:1795	Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.
32986846	11	55	theme	important	1752:1760	arg1	glycosylation					1732:1744	protein glycosylation	1724:1744	protein glycosylation	1724:1744	Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.
32986846	7	56	from	glycans	1047:1053	arg1	cortex					1058:1063	cortex	1058:1063	cortex	1058:1063	Two glycans in cortex and four in hippocampus showed different levels in AD compared to control brain.
32986846	4	57	theme	AD	767:768	arg1	brain					782:786	AD and control brain	767:786	brain	782:786	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	9	58	theme	AD	1369:1370	arg1	brain					1372:1376	AD brain	1369:1376	AD brain	1369:1376	The glycans that were altered in AD brain differed from those that were altered in AD CSF.
32986846	3	59	theme	altered	442:448	arg1	pattern					464:470	altered glycosylation pattern	442:470	altered glycosylation pattern in patients with different stages of cognitive impairment, including AD	442:542	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	7	60	theme	different	1096:1104	arg1	levels					1106:1111	different levels	1096:1111	different levels in AD	1096:1117	Two glycans in cortex and four in hippocampus showed different levels in AD compared to control brain.
32986846	10	61	from	levels	1481:1486	arg1	cortex					1512:1517	cortex	1512:1517	cortex	1512:1517	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	61	from	levels	1481:1486	arg1	hippocampus					1496:1506	hippocampus	1496:1506	hippocampus	1496:1506	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	10	61	from	levels	1481:1486	arg1	present					1450:1456	present	1450:1456	present	1450:1456	One glycan found to be present in significantly lower levels in both hippocampus and cortex in AD compared to control contained a structurally and functionally interesting epitope that we assign as a terminal galactose decorated with fucose and sialic acid.
32986846	11	62	theme	protein	1724:1730	arg1	component					1762:1770	an important component	1749:1770	an important component in the development of AD	1749:1795	Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.
32986846	11	62	theme	protein	1724:1730	arg1	glycosylation					1732:1744	protein glycosylation	1724:1744	protein glycosylation	1724:1744	Altogether, these studies suggest that protein glycosylation is an important component in the development of AD and warrants further studies.
32986846	4	63	from	cortex	757:762	arg1	brain					782:786	AD and control brain	767:786	brain	782:786	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	3	64	theme	glycosylation	450:462	arg1	pattern					464:470	altered glycosylation pattern	442:470	altered glycosylation pattern in patients with different stages of cognitive impairment, including AD	442:542	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	5	65	theme	liquid	867:872	arg1	LC-MS/MS					915:922	LC-MS/MS	915:922	LC-MS/MS	915:922	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	5	65	theme	liquid	867:872	arg1	spectrometry					901:912	liquid chromatography-tandem mass spectrometry	867:912	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	867:923	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	1	66	theme	Alzheimer	207:215	arg1	AD					226:227	AD	226:227	AD	226:227	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	1	66	theme	Alzheimer	207:215	arg1	disease					217:223	Alzheimer disease	207:223	Alzheimer disease (AD)	207:228	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	1	67	from	disease	217:223	arg1	defective					194:202	defective	194:202	defective	194:202	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	4	68	theme	glycan	723:728	arg1	consequence					580:590	a consequence	578:590	a consequence	578:590	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	4	68	theme	glycan	723:728	arg1	profile					730:736	the asparagine-linked (N-linked) glycan profile	690:736	the asparagine-linked (N-linked) glycan profile	690:736	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	4	69	from	hippocampus	741:751	arg1	brain					782:786	AD and control brain	767:786	brain	782:786	As a consequence, we hypothesized that the glycan profile is altered in the brain of patients with AD and analyzed the asparagine-linked (N-linked) glycan profile in hippocampus and cortex in AD and control brain.
32986846	1	70	theme	central	121:127	arg1	system					137:142	the central nervous system	117:142	the central nervous system	117:142	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	1	71	theme	nervous	129:135	arg1	system					137:142	the central nervous system	117:142	the central nervous system	117:142	Protein glycosylation is crucial for the central nervous system and brain functions, including processes that are defective in Alzheimer disease (AD) such as neurogenesis, synaptic function, and memory formation.
32986846	3	72	theme	fluid	408:412	arg1	studies					383:389	Glycomics studies	373:389	Glycomics studies of cerebrospinal fluid (CSF)	373:418	Glycomics studies of cerebrospinal fluid (CSF) have previously shown altered glycosylation pattern in patients with different stages of cognitive impairment, including AD, compared to healthy controls.
32986846	8	73	theme	AD	1193:1194	arg1	brain					1196:1200	AD brain	1193:1200	AD brain	1193:1200	All glycans that differed between controls and AD brain had similar structures with one sialic acid, at least one fucose and a confirmed or potential bisecting N-acetylglucosamine (GlcNAc).
32986846	5	74	theme	brain	831:835	arg1	glycoproteins					837:849	brain glycoproteins	831:849	brain glycoproteins	831:849	Glycans were enzymatically liberated from brain glycoproteins and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
32986846	7	75	from	four	1069:1072	arg1	hippocampus					1077:1087	hippocampus	1077:1087	hippocampus	1077:1087	Two glycans in cortex and four in hippocampus showed different levels in AD compared to control brain.
32544330	1	0	theme	biological	152:161	arg1	properties					163:172	altered physical and biological properties	131:172	altered physical and biological properties	131:172	Glycosylation is a common modification that can endow proteins with altered physical and biological properties.
32544330	4	1	theme	protein	716:722	arg1	thermostability					724:738	protein thermostability	716:738	protein thermostability	716:738	The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that "cap" the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability.
32544330	2	2	gly	glycosylation	283:295	arg1	residues					311:318	asparagine residues 34, 76, and 88	300:333	asparagine residues 34, 76, and 88	300:333	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	2	2	gly	glycosylation	283:295	arg1	Ribonuclease					175:186	Ribonuclease 1	175:188	Ribonuclease 1 (RNase 1)	175:198	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	2	2	gly	glycosylation	283:295	arg1	RNase					191:195	RNase 1	191:197	RNase 1	191:197	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	2	2	gly	glycosylation	283:295	arg1	homologue					220:228	the human homologue	210:228	the human homologue of the archetypal enzyme RNase A	210:261	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	3	3	theme	glycoform	472:480	arg1	structure					454:462	the structure	450:462	the structure of each glycoform	450:480	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	3	4	theme	molecular	531:539	arg1	simulations					550:560	molecular dynamics simulations	531:560	molecular dynamics simulations	531:560	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	2	5	theme	asparagine	300:309	arg1	residues					311:318	asparagine residues 34, 76, and 88	300:333	asparagine residues 34, 76, and 88	300:333	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	4	6	theme	carbonyl	654:661	arg1	groups					663:668	the carbonyl groups	650:668	the carbonyl groups	650:668	The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that "cap" the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability.
32544330	7	7	theme	protein	1053:1059	arg1	glycosylation					1061:1073	protein glycosylation	1053:1073	protein glycosylation	1053:1073	These data highlight the diverse behaviors of Man5GlcNAc2 pendants and provide a structural underpinning to the functional consequences of protein glycosylation.
32544330	6	8	gly	N-glycosylation	855:869	arg1	Asn76					874:878	Asn76	874:878	Asn76	874:878	The N-glycosylation of Asn76 has less pronounced consequences.
32544330	2	9	theme	RNase A	255:261	arg1	Ribonuclease					175:186	Ribonuclease 1	175:188	Ribonuclease 1 (RNase 1)	175:198	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	2	9	theme	RNase A	255:261	arg1	homologue					220:228	the human homologue	210:228	the human homologue of the archetypal enzyme RNase A	210:261	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	3	10	theme	core	402:405	arg1	Man5GlcNAc2					424:434	the core heptasaccharide, Man5GlcNAc2	398:434	Man5GlcNAc2	424:434	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	3	11	theme	individual	363:372	arg1	glycoforms					374:383	the three individual glycoforms	353:383	the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2	353:434	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	7	12	theme	glycosylation	1061:1073	arg1	consequences					1037:1048	the functional consequences	1022:1048	the functional consequences of protein glycosylation	1022:1073	These data highlight the diverse behaviors of Man5GlcNAc2 pendants and provide a structural underpinning to the functional consequences of protein glycosylation.
32544330	7	13	theme	functional	1026:1035	arg1	consequences					1037:1048	the functional consequences	1022:1048	the functional consequences of protein glycosylation	1022:1073	These data highlight the diverse behaviors of Man5GlcNAc2 pendants and provide a structural underpinning to the functional consequences of protein glycosylation.
32544330	3	14	theme	X-ray	503:507	arg1	scattering					509:518	small-angle X-ray scattering	491:518	small-angle X-ray scattering	491:518	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	3	15	theme	heptasaccharide	407:421	arg1	Man5GlcNAc2					424:434	the core heptasaccharide, Man5GlcNAc2	398:434	Man5GlcNAc2	424:434	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	5	16	from	glycan	758:763	arg1	Asn88					768:772	Asn88	768:772	Asn88	768:772	In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis.
32544330	1	17	theme	common	82:87	arg1	modification					89:100	a common modification	80:100	a common modification that can endow proteins with altered physical and biological properties	80:172	Glycosylation is a common modification that can endow proteins with altered physical and biological properties.
32544330	1	17	theme	common	82:87	arg1	Glycosylation					63:75	Glycosylation	63:75	Glycosylation	63:75	Glycosylation is a common modification that can endow proteins with altered physical and biological properties.
32544330	5	18	theme	enzymic	809:815	arg1	site					824:827	the enzymic active site	805:827	the enzymic active site	805:827	In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis.
32544330	3	19	theme	small-angle	491:501	arg1	scattering					509:518	small-angle X-ray scattering	491:518	small-angle X-ray scattering	491:518	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	2	20	theme	N-linked	274:281	arg1	glycosylation					283:295	N-linked glycosylation	274:295	N-linked glycosylation	274:295	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	5	21	theme	active	817:822	arg1	site					824:827	the enzymic active site	805:827	the enzymic active site	805:827	In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis.
32544330	0	22	theme	Human	41:45	arg1	Ribonuclease					47:58	N-Glycosylated Human Ribonuclease 1	26:60	N-Glycosylated Human Ribonuclease 1	26:60	Structure and Dynamics of N-Glycosylated Human Ribonuclease 1.
32544330	6	23	theme	pronounced	889:898	arg1	consequences					900:911	less pronounced consequences	884:911	less pronounced consequences	884:911	The N-glycosylation of Asn76 has less pronounced consequences.
32544330	2	24	theme	human	214:218	arg1	Ribonuclease					175:186	Ribonuclease 1	175:188	Ribonuclease 1 (RNase 1)	175:198	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	2	24	theme	human	214:218	arg1	homologue					220:228	the human homologue	210:228	the human homologue of the archetypal enzyme RNase A	210:261	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	0	25	theme	N-Glycosylated	26:39	arg1	Ribonuclease					47:58	N-Glycosylated Human Ribonuclease 1	26:60	N-Glycosylated Human Ribonuclease 1	26:60	Structure and Dynamics of N-Glycosylated Human Ribonuclease 1.
32544330	7	26	theme	Man5GlcNAc2	960:970	arg1	pendants					972:979	Man5GlcNAc2 pendants	960:979	Man5GlcNAc2 pendants	960:979	These data highlight the diverse behaviors of Man5GlcNAc2 pendants and provide a structural underpinning to the functional consequences of protein glycosylation.
32544330	2	27	link	N-linked	274:281	arg1	glycosylation					283:295	N-linked glycosylation	274:295	N-linked glycosylation	274:295	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	7	28	theme	pendants	972:979	arg1	behaviors					947:955	the diverse behaviors	935:955	the diverse behaviors of Man5GlcNAc2 pendants	935:979	These data highlight the diverse behaviors of Man5GlcNAc2 pendants and provide a structural underpinning to the functional consequences of protein glycosylation.
32544330	0	29	theme	Ribonuclease	47:58	arg1	Dynamics					14:21	Dynamics	14:21	Dynamics	14:21	Structure and Dynamics of N-Glycosylated Human Ribonuclease 1.
32544330	0	29	theme	Ribonuclease	47:58	arg1	Structure					0:8	Structure	0:8	Structure	0:8	Structure and Dynamics of N-Glycosylated Human Ribonuclease 1.
32544330	6	30	theme	Asn76	874:878	arg1	N-glycosylation					855:869	The N-glycosylation	851:869	The N-glycosylation of Asn76	851:878	The N-glycosylation of Asn76 has less pronounced consequences.
32544330	4	31	from	C-terminus	677:686	arg1	"					648:648	"	648:648	"	648:648	The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that "cap" the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability.
32544330	3	32	theme	dynamics	541:548	arg1	simulations					550:560	molecular dynamics simulations	531:560	molecular dynamics simulations	531:560	We have produced the three individual glycoforms that display the core heptasaccharide, Man5GlcNAc2, and analyzed the structure of each glycoform by using small-angle X-ray scattering along with molecular dynamics simulations.
32544330	2	33	theme	archetypal	237:246	arg1	RNase A					255:261	the archetypal enzyme RNase A	233:261	the archetypal enzyme RNase A	233:261	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	5	34	from	flexible	777:784	arg1	contrast					744:751	contrast	744:751	contrast	744:751	In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis.
32544330	2	35	theme	enzyme	248:253	arg1	RNase A					255:261	the archetypal enzyme RNase A	233:261	the archetypal enzyme RNase A	233:261	Ribonuclease 1 (RNase 1), which is the human homologue of the archetypal enzyme RNase A, undergoes N-linked glycosylation at asparagine residues 34, 76, and 88.
32544330	4	36	theme	α-helix	694:700	arg1	C-terminus					677:686	the C-terminus	673:686	the C-terminus of an α-helix	673:700	The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that "cap" the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability.
32544330	1	37	theme	altered	131:137	arg1	properties					163:172	altered physical and biological properties	131:172	altered physical and biological properties	131:172	Glycosylation is a common modification that can endow proteins with altered physical and biological properties.
32544330	6	38	contain	has	880:882	arg2	consequences					900:911	less pronounced consequences	884:911	less pronounced consequences	884:911	The N-glycosylation of Asn76 has less pronounced consequences.
32544330	6	38	contain	has	880:882	arg1	N-glycosylation					855:869	The N-glycosylation	851:869	The N-glycosylation of Asn76	851:878	The N-glycosylation of Asn76 has less pronounced consequences.
32544330	7	39	theme	diverse	939:945	arg1	behaviors					947:955	the diverse behaviors	935:955	the diverse behaviors of Man5GlcNAc2 pendants	935:979	These data highlight the diverse behaviors of Man5GlcNAc2 pendants and provide a structural underpinning to the functional consequences of protein glycosylation.
32544330	1	40	theme	physical	139:146	arg1	properties					163:172	altered physical and biological properties	131:172	altered physical and biological properties	131:172	Glycosylation is a common modification that can endow proteins with altered physical and biological properties.
32544330	4	41	theme	hydrogen	624:631	arg1	bonds					633:637	hydrogen bonds	624:637	hydrogen bonds that "cap" the carbonyl groups at the C-terminus of an α-helix	624:700	The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that "cap" the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability.
32544330	5	42	from	contrast	744:751	arg1	glycan					758:763	the glycan	754:763	the glycan on Asn88	754:772	In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis.
32544330	5	42	from	contrast	744:751	arg1	flexible					777:784	flexible	777:784	flexible	777:784	In contrast, the glycan on Asn88 is flexible and can even enter the enzymic active site, hindering catalysis.
32544330	4	43	from	glycan	567:572	arg1	Asn34					577:581	Asn34	577:581	Asn34	577:581	The glycan on Asn34 is relatively compact and rigid, donates hydrogen bonds that "cap" the carbonyl groups at the C-terminus of an α-helix, and enhances protein thermostability.
32890705	4	0	theme	structural	518:527	arg1	model					529:533	our structural model	514:533	our structural model	514:533	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	8	1	from	modifications	1552:1564	arg1	cells					1586:1590	cells	1586:1590	cells	1586:1590	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	6	2	gly	glycoproteins	1008:1020	arg1	glycoproteins					1008:1020	glycoproteins	1008:1020	glycoproteins	1008:1020	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	6	3	theme	tested	1095:1100	arg1	substrates					1102:1111	all tested substrates	1091:1111	all tested substrates	1091:1111	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	4	4	theme	polypeptide	599:609	arg1	moiety					611:616	the N-glycan core or polypeptide moiety	578:616	moiety	611:616	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	5	5	theme	surrounding	777:787	arg1	acids					795:799	surrounding amino acids	777:799	surrounding amino acids	777:799	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	6	6	theme	reducing	1278:1285	arg1	end					1287:1289	the reducing end	1274:1289	the reducing end of GlcNAc and Asn	1274:1307	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	2	7	contain	have	180:183	arg1	N-Glycans					170:178	N-Glycans	170:178	N-Glycans	170:178	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	2	7	contain	have	180:183	arg2	number					197:202	a different number	185:202	a different number of N-acetylglucosamine (GlcNAc)	185:234	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	6	8	with	oligosaccharide	1193:1207	arg1	asparagine					1214:1223	asparagine	1214:1223	asparagine (Asn)	1214:1229	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	6	8	with	oligosaccharide	1193:1207	arg1	oligosaccharide					1250:1264	a shorter oligosaccharide	1240:1264	a shorter oligosaccharide without the reducing end of GlcNAc and Asn	1240:1307	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	6	8	with	oligosaccharide	1193:1207	arg1	Asn					1226:1228	Asn	1226:1228	Asn	1226:1228	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	9	9	theme	GnT-V	1662:1666	arg1	action					1652:1657	the action	1648:1657	the action of GnT-V toward N-glycan cores and surrounding amino acids	1648:1716	CONCLUSIONS We identified several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids.
32890705	8	10	gly	glycoproteins	1569:1581	arg1	glycoproteins					1569:1581	glycoproteins	1569:1581	glycoproteins in cells	1569:1590	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	7	11	theme	amino	1416:1420	arg1	acids					1422:1426	surrounding amino acids	1404:1426	surrounding amino acids	1404:1426	These results suggest that V354 and K361 are involved in the recognition of N-glycan core and surrounding amino acids.
32890705	6	12	theme	substrates	966:975	arg1	types					957:961	various types	949:961	various types of substrates including oligosaccharides and glycoproteins	949:1020	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	9	13	theme	N-glycan	1675:1682	arg1	cores					1684:1688	N-glycan cores	1675:1688	N-glycan cores	1675:1688	CONCLUSIONS We identified several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids.
32890705	7	14	theme	acids	1422:1426	arg1	recognition					1371:1381	the recognition	1367:1381	the recognition of N-glycan core and surrounding amino acids	1367:1426	These results suggest that V354 and K361 are involved in the recognition of N-glycan core and surrounding amino acids.
32890705	1	15	theme	BACKGROUND	83:92	arg1	N-Glycosylation					94:108	BACKGROUND N-Glycosylation	83:108	BACKGROUND N-Glycosylation	83:108	BACKGROUND N-Glycosylation is crucial for protein folding, trafficking, and functions.
32890705	6	16	contain	had	1165:1167	arg1	K361A					1159:1163	K361A	1159:1163	K361A	1159:1163	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	6	16	contain	had	1165:1167	arg2	activity					1177:1184	reduced activity	1169:1184	reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn	1169:1307	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	6	17	theme	shorter	1242:1248	arg1	oligosaccharide					1250:1264	a shorter oligosaccharide	1240:1264	a shorter oligosaccharide without the reducing end of GlcNAc and Asn	1240:1307	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	8	18	from	cells	1586:1590	arg1	modifications					1552:1564	modifications	1552:1564	modifications of glycoproteins in cells	1552:1590	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	7	19	theme	core	1395:1398	arg1	recognition					1371:1381	the recognition	1367:1381	the recognition of N-glycan core and surrounding amino acids	1367:1426	These results suggest that V354 and K361 are involved in the recognition of N-glycan core and surrounding amino acids.
32890705	2	20	theme	GlcNAc	296:301	arg1	branch					303:308	the β1,6-linked GlcNAc branch	280:308	the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5)	280:392	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	10	21	gly	glycoproteins	1796:1808	arg1	glycoproteins					1796:1808	glycoproteins	1796:1808	glycoproteins	1796:1808	GENERAL SIGNIFICANCE Our data provide new insights into how GnT-V recognizes glycoproteins.
32890705	6	22	theme	substrate	1129:1137	arg1	preference					1139:1148	an altered substrate preference	1118:1148	an altered substrate preference	1118:1148	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	5	23	theme	amino	789:793	arg1	acids					795:799	surrounding amino acids	777:799	surrounding amino acids	777:799	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	2	24	theme	β1,6-linked	284:294	arg1	branch					303:308	the β1,6-linked GlcNAc branch	280:308	the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5)	280:392	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	5	25	theme	in	860:861	arg1	activities					881:890	the in vitro and in vivo activities	856:890	the in vitro and in vivo activities of the mutants	856:905	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	5	26	theme	point	810:814	arg1	mutants					816:822	point mutants	810:822	point mutants of these residues	810:840	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	6	27	contain	had	1053:1055	arg1	mutant					1046:1051	the V354N mutant	1036:1051	the V354N mutant	1036:1051	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	6	27	contain	had	1053:1055	arg2	activity					1078:1085	dramatically reduced activity	1057:1085	dramatically reduced activity for all tested substrates	1057:1111	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	8	28	from	glycoproteins	1569:1581	arg1	cells					1586:1590	cells	1586:1590	cells	1586:1590	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	7	29	theme	N-glycan	1386:1393	arg1	core					1395:1398	N-glycan core	1386:1398	N-glycan core	1386:1398	These results suggest that V354 and K361 are involved in the recognition of N-glycan core and surrounding amino acids.
32890705	6	30	theme	reduced	1070:1076	arg1	activity					1078:1085	dramatically reduced activity	1057:1085	dramatically reduced activity for all tested substrates	1057:1111	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	8	31	theme	residues	1539:1546	arg1	importance					1519:1528	the importance	1515:1528	the importance of these residues for modifications of glycoproteins in cells	1515:1590	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	2	32	theme	N-acetylglucosamine	207:225	arg1	number					197:202	a different number	185:202	a different number of N-acetylglucosamine (GlcNAc)	185:234	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	2	33	dep	N-acetylglucosaminyltransferase-V	343:375	arg1	GnT-V					378:382	GnT-V	378:382	GnT-V	378:382	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	2	33	dep	N-acetylglucosaminyltransferase-V	343:375	arg1	MGAT5					387:391	MGAT5	387:391	MGAT5	387:391	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	9	34	dep	CONCLUSIONS	1593:1603	arg1	identified					1608:1617	identified	1608:1617	identified several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids	1608:1716	CONCLUSIONS We identified several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids.
32890705	2	35	link	β1,6-linked	284:294	arg1	branch					303:308	the β1,6-linked GlcNAc branch	280:308	the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5)	280:392	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	5	36	theme	candidate	706:714	arg1	residues					716:723	four candidate residues	701:723	four candidate residues involved in the interaction with the glycan core or surrounding amino acids	701:799	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	5	37	dep	in	860:861	arg1	vitro					863:867	vitro	863:867	vitro	863:867	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	1	38	theme	protein	125:131	arg1	folding					133:139	protein folding	125:139	protein folding	125:139	BACKGROUND N-Glycosylation is crucial for protein folding, trafficking, and functions.
32890705	5	39	theme	residues	833:840	arg1	mutants					816:822	point mutants	810:822	point mutants of these residues	810:840	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	0	40	theme	glycan	15:20	arg1	Recognition					0:10	Recognition	0:10	Recognition of glycan and protein substrates by N-acetylglucosaminyltransferase-V	0:80	Recognition of glycan and protein substrates by N-acetylglucosaminyltransferase-V.
32890705	9	41	theme	amino	1706:1710	arg1	acids					1712:1716	surrounding amino acids	1694:1716	surrounding amino acids	1694:1716	CONCLUSIONS We identified several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids.
32890705	6	42	dep	in	920:921	arg1	vitro					923:927	vitro	923:927	vitro	923:927	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	2	43	theme	specific	313:320	arg1	proteins					322:329	specific proteins	313:329	specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5)	313:392	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	5	44	theme	in	873:874	arg1	activities					881:890	the in vitro and in vivo activities	856:890	the in vitro and in vivo activities of the mutants	856:905	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	0	45	theme	substrates	34:43	arg1	Recognition					0:10	Recognition	0:10	Recognition of glycan and protein substrates by N-acetylglucosaminyltransferase-V	0:80	Recognition of glycan and protein substrates by N-acetylglucosaminyltransferase-V.
32890705	4	46	theme	N-glycan	582:589	arg1	core					591:594	the N-glycan core or polypeptide moiety	578:616	core	591:594	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	6	47	theme	V354N	1040:1044	arg1	mutant					1046:1051	the V354N mutant	1036:1051	the V354N mutant	1036:1051	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	2	48	theme	protein-selective	250:266	arg1	manner					268:273	a protein-selective manner	248:273	a protein-selective manner	248:273	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	3	49	theme	specific	471:478	arg1	proteins					487:494	specific target proteins	471:494	specific target proteins	471:494	However, little is known about how GnT-V acts on specific target proteins.
32890705	0	50	theme	protein	26:32	arg1	substrates					34:43	protein substrates	26:43	protein substrates	26:43	Recognition of glycan and protein substrates by N-acetylglucosaminyltransferase-V.
32890705	6	51	theme	enzyme	929:934	arg1	assays					936:941	Our in vitro enzyme assays	916:941	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins	908:1020	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	2	52	theme	different	187:195	arg1	number					197:202	a different number	185:202	a different number of N-acetylglucosamine (GlcNAc)	185:234	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	4	53	theme	N-glycan	650:657	arg1	moiety					611:616	the N-glycan core or polypeptide moiety	578:616	moiety	611:616	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	4	53	theme	N-glycan	650:657	arg1	N-glycan					650:657	N-glycan	650:657	N-glycan	650:657	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	4	53	theme	N-glycan	650:657	arg1	site					642:645	the accepter site	629:645	the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan	578:657	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	4	53	theme	N-glycan	650:657	arg1	core					591:594	the N-glycan core or polypeptide moiety	578:616	core	591:594	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	8	54	theme	glycoproteins	1569:1581	arg1	modifications					1552:1564	modifications	1552:1564	modifications of glycoproteins in cells	1552:1590	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	6	55	theme	Asn	1305:1307	arg1	end					1287:1289	the reducing end	1274:1289	the reducing end of GlcNAc and Asn	1274:1307	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	6	56	theme	various	949:955	arg1	types					957:961	various types	949:961	various types of substrates including oligosaccharides and glycoproteins	949:1020	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	8	57	theme	knockout	1481:1488	arg1	cells					1495:1499	GnT-V knockout HeLa cells	1475:1499	GnT-V knockout HeLa cells	1475:1499	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	6	58	theme	in	920:921	arg1	assays					936:941	Our in vitro enzyme assays	916:941	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins	908:1020	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	9	59	theme	surrounding	1694:1704	arg1	acids					1712:1716	surrounding amino acids	1694:1716	surrounding amino acids	1694:1716	CONCLUSIONS We identified several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids.
32890705	5	60	with	interaction	741:751	arg1	core					769:772	the glycan core	758:772	the glycan core	758:772	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	5	60	with	interaction	741:751	arg1	acids					795:799	surrounding amino acids	777:799	surrounding amino acids	777:799	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	7	61	theme	surrounding	1404:1414	arg1	acids					1422:1426	surrounding amino acids	1404:1426	surrounding amino acids	1404:1426	These results suggest that V354 and K361 are involved in the recognition of N-glycan core and surrounding amino acids.
32890705	5	62	theme	mutants	899:905	arg1	activities					881:890	the in vitro and in vivo activities	856:890	the in vitro and in vivo activities of the mutants	856:905	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	6	63	theme	GlcNAc	1294:1299	arg1	end					1287:1289	the reducing end	1274:1289	the reducing end of GlcNAc and Asn	1274:1307	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	8	64	theme	rescue	1450:1455	arg1	experiments					1457:1467	rescue experiments	1450:1467	rescue experiments using GnT-V knockout HeLa cells	1450:1499	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	9	65	theme	several	1619:1625	arg1	residues					1627:1634	several residues	1619:1634	several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids	1619:1716	CONCLUSIONS We identified several residues involved in the action of GnT-V toward N-glycan cores and surrounding amino acids.
32890705	6	66	theme	altered	1121:1127	arg1	preference					1139:1148	an altered substrate preference	1118:1148	an altered substrate preference	1118:1148	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	5	67	dep	in	873:874	arg1	vivo					876:879	vivo	876:879	vivo	876:879	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	10	68	theme	SIGNIFICANCE	1727:1738	arg1	data					1744:1747	GENERAL SIGNIFICANCE Our data	1719:1747	GENERAL SIGNIFICANCE Our data	1719:1747	GENERAL SIGNIFICANCE Our data provide new insights into how GnT-V recognizes glycoproteins.
32890705	6	69	theme	reduced	1169:1175	arg1	activity					1177:1184	reduced activity	1169:1184	reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn	1169:1307	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	8	70	theme	GnT-V	1475:1479	arg1	cells					1495:1499	GnT-V knockout HeLa cells	1475:1499	GnT-V knockout HeLa cells	1475:1499	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	5	71	theme	glycan	762:767	arg1	core					769:772	the glycan core	758:772	the glycan core	758:772	To explore this possibility, we selected four candidate residues involved in the interaction with the glycan core or surrounding amino acids, created point mutants of these residues, and examined the in vitro and in vivo activities of the mutants.
32890705	3	72	theme	target	480:485	arg1	proteins					487:494	specific target proteins	471:494	specific target proteins	471:494	However, little is known about how GnT-V acts on specific target proteins.
32890705	2	73	theme	cancer	403:408	arg1	malignancy					410:419	cancer malignancy	403:419	cancer malignancy	403:419	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	2	74	from	branch	303:308	arg1	proteins					322:329	specific proteins	313:329	specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5)	313:392	N-Glycans have a different number of N-acetylglucosamine (GlcNAc) branches in a protein-selective manner, and the β1,6-linked GlcNAc branch on specific proteins produced by N-acetylglucosaminyltransferase-V (GnT-V or MGAT5) promotes cancer malignancy.
32890705	4	75	theme	accepter	633:640	arg1	N-glycan					650:657	N-glycan	650:657	N-glycan	650:657	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	4	75	theme	accepter	633:640	arg1	site					642:645	the accepter site	629:645	the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan	578:657	METHODS Based on our structural model, we hypothesized that GnT-V interacts with the N-glycan core or polypeptide moiety as well as the accepter site of N-glycan.
32890705	6	76	dep	RESULTS	908:914	arg1	assays					936:941	Our in vitro enzyme assays	916:941	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins	908:1020	RESULTS Our in vitro enzyme assays using various types of substrates including oligosaccharides and glycoproteins revealed that the V354N mutant had dramatically reduced activity for all tested substrates with an altered substrate preference and that K361A had reduced activity for an oligosaccharide with asparagine (Asn), but not a shorter oligosaccharide without the reducing end of GlcNAc and Asn.
32890705	8	77	theme	HeLa	1490:1493	arg1	cells					1495:1499	GnT-V knockout HeLa cells	1475:1499	GnT-V knockout HeLa cells	1475:1499	We further performed rescue experiments using GnT-V knockout HeLa cells and confirmed the importance of these residues for modifications of glycoproteins in cells.
32890705	10	78	theme	GENERAL	1719:1725	arg1	data					1744:1747	GENERAL SIGNIFICANCE Our data	1719:1747	GENERAL SIGNIFICANCE Our data	1719:1747	GENERAL SIGNIFICANCE Our data provide new insights into how GnT-V recognizes glycoproteins.
32890705	10	79	theme	new	1757:1759	arg1	insights					1761:1768	new insights	1757:1768	new insights into how GnT-V recognizes glycoproteins	1757:1808	GENERAL SIGNIFICANCE Our data provide new insights into how GnT-V recognizes glycoproteins.
33664361	5	0	theme	envelope	745:752	arg1	protein					758:764	the viral envelope (E) protein	735:764	the viral envelope (E) protein	735:764	In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method.
33664361	6	1	theme	deamidated	984:993	arg1	asparagine					995:1004	deamidated asparagine	984:1004	deamidated asparagine at the potential N-glycosylation site N444	984:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	7	2	theme	E	1092:1092	arg1	protein					1094:1100	the ZIKV E protein	1083:1100	the ZIKV E protein	1083:1100	This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity.
33664361	6	3	theme	N-glycosylation	1023:1037	arg1	site					1039:1042	the potential N-glycosylation site N444	1009:1047	the potential N-glycosylation site N444	1009:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	1	4	theme	N-glycosylation	144:158	arg1	analysis					160:167	a site-specific N-glycosylation analysis	128:167	a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain	128:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	10	5	theme	human	1529:1533	arg1	pathogenicity					1535:1547	human pathogenicity	1529:1547	human pathogenicity	1529:1547	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	6	6	theme	glycopeptide	966:977	arg1	MS-signal					942:950	a strong MS-signal	933:950	a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444	933:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	10	7	theme	protein	1487:1493	arg1	glycosylation					1495:1507	protein glycosylation	1487:1507	protein glycosylation	1487:1507	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	6	8	theme	enzymatic	876:884	arg1	de-N-glycosylation					886:903	enzymatic de-N-glycosylation	876:903	enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444	876:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	7	9	theme	protein	1094:1100	arg1	site					1075:1078	this site	1070:1078	this site of the ZIKV E protein	1070:1100	This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity.
33664361	7	9	theme	protein	1094:1100	arg1	protein					1094:1100	the ZIKV E protein	1083:1100	the ZIKV E protein	1083:1100	This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity.
33664361	3	10	theme	LC-MS/MS-based	472:485	arg1	workflow					487:494	a LC-MS/MS-based workflow	470:494	a LC-MS/MS-based workflow	470:494	Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC-MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software.
33664361	6	11	theme	former	959:964	arg1	glycopeptide					966:977	the former glycopeptide	955:977	the former glycopeptide	955:977	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	4	12	gly	glycosylated	629:640	arg1	protein					609:615	The viral non-structural protein 1	584:617	The viral non-structural protein 1 (NS1)	584:623	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	4	12	gly	glycosylated	629:640	arg1	sites					717:721	both potential N-glycosylation sites	686:721	both potential N-glycosylation sites	686:721	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	4	12	gly	glycosylated	629:640	arg1	NS1					620:622	NS1	620:622	NS1	620:622	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	4	12	gly	glycosylated	629:640	arg2	sites					717:721	both potential N-glycosylation sites	686:721	both potential N-glycosylation sites	686:721	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	4	12	gly	glycosylated	629:640	arg2	protein					609:615	The viral non-structural protein 1	584:617	The viral non-structural protein 1 (NS1)	584:623	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	4	12	gly	glycosylated	629:640	arg2	NS1					620:622	NS1	620:622	NS1	620:622	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	1	13	from	analysis	160:167	arg1	strain					216:221	a Brazilian Zika virus (ZIKV) strain	186:221	a Brazilian Zika virus (ZIKV) strain	186:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	9	14	gly	glycosylation	1371:1383	arg1	antigens					1394:1401	major antigens	1388:1401	major antigens	1388:1401	It allows to better characterize viral isolates, and to monitor glycosylation of major antigens.
33664361	7	15	theme	ZIKV	1087:1090	arg1	protein					1094:1100	the ZIKV E protein	1083:1100	the ZIKV E protein	1083:1100	This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity.
33664361	6	16	with	de-N-glycosylation	886:903	arg1	F					917:917	PNGase F	910:917	PNGase F	910:917	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	10	17	theme	influenza	1575:1583	arg1	virus					1585:1589	influenza virus	1575:1589	influenza virus	1575:1589	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	9	18	theme	major	1388:1392	arg1	antigens					1394:1401	major antigens	1388:1401	major antigens	1388:1401	It allows to better characterize viral isolates, and to monitor glycosylation of major antigens.
33664361	3	19	theme	different	438:446	arg1	enzymes					448:454	different enzymes	438:454	different enzymes	438:454	Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC-MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software.
33664361	2	20	theme	high	254:257	arg1	yield					259:263	high yield	254:263	high yield	254:263	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	2	21	theme	g-force	341:347	arg1	centrifugation					363:376	g-force step-gradient centrifugation	341:376	g-force step-gradient centrifugation	341:376	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	5	22	theme	E	755:755	arg1	protein					758:764	the viral envelope (E) protein	735:764	the viral envelope (E) protein	735:764	In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method.
33664361	5	23	theme	specific	770:777	arg1	N-glycans					779:787	no specific N-glycans	767:787	no specific N-glycans	767:787	In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method.
33664361	1	24	theme	proteins	172:179	arg1	analysis					160:167	a site-specific N-glycosylation analysis	128:167	a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain	128:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	0	25	theme	N-glycosylation	14:28	arg1	analysis					30:37	Site-specific N-glycosylation analysis	0:37	Site-specific N-glycosylation analysis of animal cell	0:52	Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins.
33664361	2	26	theme	cell	291:294	arg1	line					296:299	an embryo-derived stem cell line	268:299	an embryo-derived stem cell line (EB66, Valneva SE)	268:318	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	7	27	theme	high	1141:1144	arg1	micro-heterogeneity					1146:1164	very high micro-heterogeneity	1136:1164	very high micro-heterogeneity	1136:1164	This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity.
33664361	0	28	theme	Site-specific	0:12	arg1	analysis					30:37	Site-specific N-glycosylation analysis	0:37	Site-specific N-glycosylation analysis of animal cell	0:52	Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins.
33664361	8	29	theme	site-specific	1224:1236	arg1	analysis					1254:1261	site-specific N-glycosylation analysis	1224:1261	site-specific N-glycosylation analysis of viral proteins, i.e.	1224:1285	Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV.
33664361	6	30	from	site	1039:1042	arg1	asparagine					995:1004	deamidated asparagine	984:1004	deamidated asparagine at the potential N-glycosylation site N444	984:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	2	31	theme	stem	286:289	arg1	line					296:299	an embryo-derived stem cell line	268:299	an embryo-derived stem cell line (EB66, Valneva SE)	268:318	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	8	32	theme	N-glycosylation	1238:1252	arg1	analysis					1254:1261	site-specific N-glycosylation analysis	1224:1261	site-specific N-glycosylation analysis of viral proteins, i.e.	1224:1285	Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV.
33664361	6	33	theme	strong	935:940	arg1	MS-signal					942:950	a strong MS-signal	933:950	a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444	933:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	6	34	gly	N-glycosylation	1023:1037	arg2	site					1039:1042	the potential N-glycosylation site N444	1009:1047	the potential N-glycosylation site N444	1009:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	6	34	gly	N-glycosylation	1023:1037	arg2	N444					1044:1047	N444	1044:1047	N444	1044:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	2	35	theme	embryo-derived	271:284	arg1	line					296:299	an embryo-derived stem cell line	268:299	an embryo-derived stem cell line (EB66, Valneva SE)	268:318	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	10	36	theme	detailed	1446:1453	arg1	studies					1455:1461	detailed studies	1446:1461	detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus	1446:1611	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	1	37	theme	Brazilian	188:196	arg1	strain					216:221	a Brazilian Zika virus (ZIKV) strain	186:221	a Brazilian Zika virus (ZIKV) strain	186:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	2	38	dep	line	296:299	arg1	EB66					302:305	EB66	302:305	EB66	302:305	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	9	39	theme	viral	1340:1344	arg1	isolates					1346:1353	viral isolates	1340:1353	viral isolates	1340:1353	It allows to better characterize viral isolates, and to monitor glycosylation of major antigens.
33664361	6	40	with	MS-signal	942:950	arg1	asparagine					995:1004	deamidated asparagine	984:1004	deamidated asparagine at the potential N-glycosylation site N444	984:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	10	41	theme	many	1552:1555	arg1	corona					1600:1605	corona	1600:1605	corona	1600:1605	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	10	41	theme	many	1552:1555	arg1	HIV					1592:1594	HIV	1592:1594	HIV	1592:1594	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	10	41	theme	many	1552:1555	arg1	viruses					1557:1563	many viruses	1552:1563	many viruses including influenza virus, HIV and corona virus	1552:1611	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	10	41	theme	many	1552:1555	arg1	virus					1585:1589	influenza virus	1575:1589	influenza virus	1575:1589	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	1	42	theme	Zika	198:201	arg1	strain					216:221	a Brazilian Zika virus (ZIKV) strain	186:221	a Brazilian Zika virus (ZIKV) strain	186:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	0	43	theme	cell	49:52	arg1	analysis					30:37	Site-specific N-glycosylation analysis	0:37	Site-specific N-glycosylation analysis of animal cell	0:52	Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins.
33664361	4	44	gly	N-glycosylation	701:715	arg2	sites					717:721	both potential N-glycosylation sites	686:721	both potential N-glycosylation sites	686:721	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	6	45	theme	potential	1013:1021	arg1	site					1039:1042	the potential N-glycosylation site N444	1009:1047	the potential N-glycosylation site N444	1009:1047	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	3	46	theme	glyXtoolMS	563:572	arg1	software					574:581	the in-house developed glyXtoolMS software	540:581	the in-house developed glyXtoolMS software	540:581	Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC-MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software.
33664361	1	47	theme	virus	203:207	arg1	strain					216:221	a Brazilian Zika virus (ZIKV) strain	186:221	a Brazilian Zika virus (ZIKV) strain	186:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	0	48	theme	animal	42:47	arg1	cell					49:52	animal cell	42:52	animal cell	42:52	Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins.
33664361	2	49	link	embryo-derived	271:284	arg1	line					296:299	an embryo-derived stem cell line	268:299	an embryo-derived stem cell line (EB66, Valneva SE)	268:318	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	10	50	dep	virus	1585:1589	arg1	virus					1607:1611	virus	1607:1611	virus	1607:1611	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	8	51	gly	N-glycosylation	1238:1252	arg1	proteins					1272:1279	viral proteins	1266:1279	viral proteins	1266:1279	Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV.
33664361	0	52	gly	N-glycosylation	14:28	arg1	cell					49:52	animal cell	42:52	animal cell	42:52	Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins.
33664361	2	53	theme	step-gradient	349:361	arg1	centrifugation					363:376	g-force step-gradient centrifugation	341:376	g-force step-gradient centrifugation	341:376	The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation.
33664361	0	54	theme	Zika	70:73	arg1	proteins					81:88	Zika virus proteins	70:88	Zika virus proteins	70:88	Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins.
33664361	1	55	from	strain	216:221	arg1	proteins					172:179	proteins	172:179	proteins from a Brazilian Zika virus (ZIKV) strain	172:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	1	55	from	strain	216:221	arg1	analysis					160:167	a site-specific N-glycosylation analysis	128:167	a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain	128:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	5	56	theme	viral	739:743	arg1	protein					758:764	the viral envelope (E) protein	735:764	the viral envelope (E) protein	735:764	In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method.
33664361	3	57	theme	in-house	544:551	arg1	software					574:581	the in-house developed glyXtoolMS software	540:581	the in-house developed glyXtoolMS software	540:581	Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC-MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software.
33664361	6	58	gly	glycopeptide	966:977	arg2	glycopeptide					966:977	the former glycopeptide	955:977	the former glycopeptide	955:977	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	4	59	theme	potential	691:699	arg1	sites					717:721	both potential N-glycosylation sites	686:721	both potential N-glycosylation sites	686:721	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	10	60	theme	glycosylation	1495:1507	arg1	impact					1477:1482	the impact	1473:1482	the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus	1473:1611	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	3	61	theme	developed	553:561	arg1	software					574:581	the in-house developed glyXtoolMS software	540:581	the in-house developed glyXtoolMS software	540:581	Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC-MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software.
33664361	1	62	theme	first	116:120	arg1	time					122:125	the first time	112:125	the first time	112:125	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	6	63	theme	PNGase	910:915	arg1	F					917:917	PNGase F	910:917	PNGase F	910:917	Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444.
33664361	7	64	gly	N-glycosylated	1112:1125	arg1	site					1075:1078	this site	1070:1078	this site of the ZIKV E protein	1070:1100	This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity.
33664361	7	64	gly	N-glycosylated	1112:1125	arg1	protein					1094:1100	the ZIKV E protein	1083:1100	the ZIKV E protein	1083:1100	This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity.
33664361	3	65	theme	semi-automated	515:528	arg1	way					530:532	a semi-automated way	513:532	a semi-automated way using the in-house developed glyXtoolMS software	513:581	Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC-MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software.
33664361	1	66	theme	ZIKV	210:213	arg1	strain					216:221	a Brazilian Zika virus (ZIKV) strain	186:221	a Brazilian Zika virus (ZIKV) strain	186:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	1	67	gly	N-glycosylation	144:158	arg1	proteins					172:179	proteins	172:179	proteins from a Brazilian Zika virus (ZIKV) strain	172:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	4	68	theme	N-glycosylation	701:715	arg1	sites					717:721	both potential N-glycosylation sites	686:721	both potential N-glycosylation sites	686:721	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	10	69	from	impact	1477:1482	arg1	antigenicity					1512:1523	antigenicity	1512:1523	antigenicity	1512:1523	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	10	69	from	impact	1477:1482	arg1	pathogenicity					1535:1547	human pathogenicity	1529:1547	human pathogenicity	1529:1547	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	10	70	theme	viruses	1557:1563	arg1	antigenicity					1512:1523	antigenicity	1512:1523	antigenicity	1512:1523	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	10	70	theme	viruses	1557:1563	arg1	pathogenicity					1535:1547	human pathogenicity	1529:1547	human pathogenicity	1529:1547	The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
33664361	8	71	theme	proteins	1272:1279	arg1	analysis					1254:1261	site-specific N-glycosylation analysis	1224:1261	site-specific N-glycosylation analysis of viral proteins, i.e.	1224:1285	Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV.
33664361	8	72	theme	viral	1266:1270	arg1	proteins					1272:1279	viral proteins	1266:1279	viral proteins	1266:1279	Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV.
33664361	4	73	theme	high-mannose	659:670	arg1	structures					672:681	high-mannose structures	659:681	high-mannose structures	659:681	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	8	74	theme	Brazilian	1291:1299	arg1	ZIKV					1301:1304	Brazilian ZIKV	1291:1304	Brazilian ZIKV	1291:1304	Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV.
33664361	4	75	theme	non-structural	594:607	arg1	protein					609:615	The viral non-structural protein 1	584:617	The viral non-structural protein 1 (NS1)	584:623	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	4	75	theme	non-structural	594:607	arg1	NS1					620:622	NS1	620:622	NS1	620:622	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	0	76	theme	virus	75:79	arg1	proteins					81:88	Zika virus proteins	70:88	Zika virus proteins	70:88	Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins.
33664361	9	77	theme	antigens	1394:1401	arg1	glycosylation					1371:1383	glycosylation	1371:1383	glycosylation of major antigens	1371:1401	It allows to better characterize viral isolates, and to monitor glycosylation of major antigens.
33664361	1	78	theme	site-specific	130:142	arg1	analysis					160:167	a site-specific N-glycosylation analysis	128:167	a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain	128:221	Here, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain.
33664361	4	79	theme	viral	588:592	arg1	protein					609:615	The viral non-structural protein 1	584:617	The viral non-structural protein 1 (NS1)	584:623	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33664361	4	79	theme	viral	588:592	arg1	NS1					620:622	NS1	620:622	NS1	620:622	The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites.
33560857	10	0	theme	MassIVE	1751:1757	arg1	repository					1759:1768	the MassIVE repository	1747:1768	the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X]	1747:1824	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	4	1	theme	present	626:632	arg1	study					634:638	The present study	622:638	The present study	622:638	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	10	2	theme	identifier	1779:1788	arg1	MSV000086774					1790:1801	the identifier MSV000086774	1775:1801	the identifier MSV000086774 [DOI: 10.25345/C5Z50X]	1775:1824	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	5	3	theme	specific	912:919	arg1	trypsin					938:944	trypsin	938:944	trypsin	938:944	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	5	3	theme	specific	912:919	arg1	Glu-C					962:966	endoproteinase Glu-C	947:966	endoproteinase Glu-C	947:966	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	5	3	theme	specific	912:919	arg1	enzymes					921:927	specific enzymes	912:927	specific enzymes	912:927	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	5	3	theme	specific	912:919	arg1	enzyme					989:994	the nonspecific enzyme	973:994	the nonspecific enzyme	973:994	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	8	4	theme	notable	1276:1282	arg1	differences					1284:1294	notable differences	1276:1294	notable differences	1276:1294	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	10	5	theme	spectrometric	1638:1650	arg1	data					1652:1655	Raw mass spectrometric data	1629:1655	Raw mass spectrometric data	1629:1655	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	1	6	link	N-linked	251:258	arg1	glycosylation					260:272	N-linked glycosylation	251:272	N-linked glycosylation	251:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	10	7	theme	Raw	1629:1631	arg1	data					1652:1655	Raw mass spectrometric data	1629:1655	Raw mass spectrometric data	1629:1655	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	5	8	theme	multienzymatic	873:886	arg1	approach					898:905	a multienzymatic digestion approach	871:905	a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS	871:1051	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	9	9	dep	cancer	1594:1599	arg1	progression					1601:1611	progression	1601:1611	progression	1601:1611	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	4	10	theme	colon	685:689	arg1	carcinoma					691:699	human colon carcinoma	679:699	human colon carcinoma	679:699	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	10	11	theme	processed	1669:1677	arg1	files					1684:1688	Skyline processed data files	1661:1688	Skyline processed data files that support the findings of this study	1661:1728	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	1	12	gly	N-glycosylation	164:178	arg2	28					151:152	28	151:152	28	151:152	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	12	gly	N-glycosylation	164:178	arg2	sites					180:184	28 potential N-glycosylation sites	151:184	28 potential N-glycosylation sites	151:184	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	8	13	theme	N-glycosylation	1318:1332	arg1	sites					1334:1338	certain N-glycosylation sites	1310:1338	certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor	1310:1390	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	1	14	theme	potential	154:162	arg1	sites					180:184	28 potential N-glycosylation sites	151:184	28 potential N-glycosylation sites	151:184	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	9	15	theme	improved	1544:1551	arg1	diagnostics					1553:1563	improved diagnostics	1544:1563	improved diagnostics	1544:1563	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	8	16	theme	metastatic	1375:1384	arg1	tumor					1386:1390	metastatic tumor	1375:1390	metastatic tumor	1375:1390	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	0	17	theme	Capillary	94:102	arg1	Spectrometry					132:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	0	18	theme	Mass	127:130	arg1	Spectrometry					132:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	4	19	gly	N-glycosylation	787:801	arg2	sites					803:807	21 out of 28 potential N-glycosylation sites	764:807	21 out of 28 potential N-glycosylation sites	764:807	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	4	19	gly	N-glycosylation	787:801	arg2	28					774:775	28	774:775	28	774:775	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	9	20	theme	cancer	1594:1599	arg1	monitoring					1569:1578	monitoring	1569:1578	monitoring	1569:1578	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	9	20	theme	cancer	1594:1599	arg1	diagnostics					1553:1563	improved diagnostics	1544:1563	improved diagnostics	1544:1563	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	6	21	theme	N-glycan	1109:1116	arg1	compositions					1118:1129	128 unique N-glycan compositions	1098:1129	128 unique N-glycan compositions	1098:1129	In total, 893 different N-glycopeptides and 128 unique N-glycan compositions were identified.
33560857	0	22	theme	Sheathless	83:92	arg1	Spectrometry					132:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	2	23	theme	many	402:405	arg1	tumors					413:418	many solid tumors	402:418	many solid tumors	402:418	CEA is often overexpressed and released by many solid tumors, including colorectal carcinomas.
33560857	2	23	theme	many	402:405	arg1	carcinomas					442:451	colorectal carcinomas	431:451	colorectal carcinomas	431:451	CEA is often overexpressed and released by many solid tumors, including colorectal carcinomas.
33560857	0	24	theme	Site-Specific	0:12	arg1	Analysis					37:44	Site-Specific N-Linked Glycosylation Analysis	0:44	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.	0:144	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	5	25	theme	nonspecific	977:987	arg1	enzyme					989:994	the nonspecific enzyme	973:994	the nonspecific enzyme	973:994	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	5	25	theme	nonspecific	977:987	arg1	Pronase					997:1003	Pronase	997:1003	Pronase	997:1003	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	6	26	gly	N-glycopeptides	1078:1092	arg2	N-glycopeptides					1078:1092	893 different N-glycopeptides	1064:1092	893 different N-glycopeptides	1064:1092	In total, 893 different N-glycopeptides and 128 unique N-glycan compositions were identified.
33560857	4	27	theme	N-glycosylation	787:801	arg1	sites					803:807	21 out of 28 potential N-glycosylation sites	764:807	21 out of 28 potential N-glycosylation sites	764:807	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	10	28	theme	study	1724:1728	arg1	findings					1707:1714	the findings	1703:1714	the findings of this study	1703:1728	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	0	29	theme	Glycosylation	23:35	arg1	Analysis					37:44	Site-Specific N-Linked Glycosylation Analysis	0:44	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.	0:144	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	1	30	theme	mass	314:317	arg1	mass					314:317	its molecular mass	300:317	its molecular mass	300:317	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	30	theme	mass	314:317	arg1	%					295:295	approximately 60%	279:295	approximately 60% of its molecular mass	279:317	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	9	31	dep	investigated	1485:1496	arg1	if					1474:1475	if	1474:1475	if	1474:1475	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	3	32	theme	impressive	470:479	arg1	heterogeneity					481:493	impressive heterogeneity	470:493	impressive heterogeneity	470:493	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	3	33	from	heterogeneity	481:493	arg1	content					520:526	sugar content	514:526	sugar content	514:526	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	0	34	theme	Carcinoembryonic	55:70	arg1	Antigen					72:78	Human Carcinoembryonic Antigen	49:78	Human Carcinoembryonic Antigen	49:78	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	10	35	with	repository	1759:1768	arg1	MSV000086774					1790:1801	the identifier MSV000086774	1775:1801	the identifier MSV000086774 [DOI: 10.25345/C5Z50X]	1775:1824	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	3	36	from	variability	499:509	arg1	content					520:526	sugar content	514:526	sugar content	514:526	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	1	37	theme	N-linked	251:258	arg1	glycosylation					260:272	N-linked glycosylation	251:272	N-linked glycosylation	251:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	3	38	theme	carbohydrate	568:579	arg1	structures					581:590	carbohydrate structures	568:590	carbohydrate structures	568:590	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	3	39	dep	heterogeneity	481:493	arg1	an					467:468	an	467:468	an	467:468	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	1	40	theme	human	187:191	arg1	CEA					219:221	CEA	219:221	CEA	219:221	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	40	theme	human	187:191	arg1	antigen					210:216	human carcinoembryonic antigen	187:216	human carcinoembryonic antigen (CEA)	187:222	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	3	41	theme	site-specific	538:550	arg1	distribution					552:563	site-specific distribution	538:563	site-specific distribution of carbohydrate structures	538:590	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	4	42	theme	CEA	653:655	arg1	samples					657:663	CEA samples	653:663	CEA samples purified from human colon carcinoma and human liver metastases	653:726	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	7	43	theme	great	1159:1163	arg1	heterogeneity					1165:1177	a great heterogeneity	1157:1177	a great heterogeneity	1157:1177	Overall, a great heterogeneity was found both within (micro) and in between (macro) individual N-glycosylation sites.
33560857	10	44	from	available	1734:1742	arg1	repository					1759:1768	the MassIVE repository	1747:1768	the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X]	1747:1824	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	1	45	theme	extreme	233:239	arg1	amount					241:246	an extreme amount	230:246	an extreme amount of N-linked glycosylation	230:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	45	theme	extreme	233:239	arg1	glycosylation					260:272	N-linked glycosylation	251:272	N-linked glycosylation	251:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	3	46	theme	structures	581:590	arg1	distribution					552:563	site-specific distribution	538:563	site-specific distribution of carbohydrate structures	538:590	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	4	47	theme	liver	711:715	arg1	metastases					717:726	human liver metastases	705:726	human liver metastases	705:726	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	10	48	from	repository	1759:1768	arg1	available					1734:1742	available	1734:1742	available	1734:1742	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	7	49	theme	individual	1232:1241	arg1	sites					1259:1263	between (macro) individual N-glycosylation sites	1216:1263	between (macro) individual N-glycosylation sites	1216:1263	Overall, a great heterogeneity was found both within (micro) and in between (macro) individual N-glycosylation sites.
33560857	4	50	theme	human	705:709	arg1	metastases					717:726	human liver metastases	705:726	human liver metastases	705:726	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	10	51	theme	mass	1633:1636	arg1	data					1652:1655	Raw mass spectrometric data	1629:1655	Raw mass spectrometric data	1629:1655	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	10	52	theme	data	1679:1682	arg1	files					1684:1688	Skyline processed data files	1661:1688	Skyline processed data files that support the findings of this study	1661:1728	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	5	53	theme	digestion	888:896	arg1	approach					898:905	a multienzymatic digestion approach	871:905	a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS	871:1051	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	4	54	theme	human	679:683	arg1	carcinoma					691:699	human colon carcinoma	679:699	human colon carcinoma	679:699	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	10	55	theme	Skyline	1661:1667	arg1	files					1684:1688	Skyline processed data files	1661:1688	Skyline processed data files that support the findings of this study	1661:1728	Raw mass spectrometric data and Skyline processed data files that support the findings of this study are available in the MassIVE repository with the identifier MSV000086774 [DOI: 10.25345/C5Z50X].
33560857	5	56	theme	endoproteinase	947:960	arg1	Glu-C					962:966	endoproteinase Glu-C	947:966	endoproteinase Glu-C	947:966	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	8	57	theme	certain	1310:1316	arg1	sites					1334:1338	certain N-glycosylation sites	1310:1338	certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor	1310:1390	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	1	58	theme	N-glycosylation	164:178	arg1	sites					180:184	28 potential N-glycosylation sites	151:184	28 potential N-glycosylation sites	151:184	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	7	59	theme	N-glycosylation	1243:1257	arg1	sites					1259:1263	between (macro) individual N-glycosylation sites	1216:1263	between (macro) individual N-glycosylation sites	1216:1263	Overall, a great heterogeneity was found both within (micro) and in between (macro) individual N-glycosylation sites.
33560857	8	60	theme	primary	1348:1354	arg1	adenocarcinoma					1356:1369	primary adenocarcinoma	1348:1369	primary adenocarcinoma	1348:1369	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	7	61	theme	macro	1225:1229	arg1	sites					1259:1263	between (macro) individual N-glycosylation sites	1216:1263	between (macro) individual N-glycosylation sites	1216:1263	Overall, a great heterogeneity was found both within (micro) and in between (macro) individual N-glycosylation sites.
33560857	0	62	theme	Electrophoresis-Tandem	104:125	arg1	Spectrometry					132:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry	83:143	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	8	63	gly	N-glycosylation	1318:1332	arg2	sites					1334:1338	certain N-glycosylation sites	1310:1338	certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor	1310:1390	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	1	64	theme	carcinoembryonic	193:208	arg1	CEA					219:221	CEA	219:221	CEA	219:221	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	64	theme	carcinoembryonic	193:208	arg1	antigen					210:216	human carcinoembryonic antigen	187:216	human carcinoembryonic antigen (CEA)	187:222	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	4	65	theme	sites	803:807	arg1	characterization					744:759	the characterization	740:759	the characterization of 21 out of 28 potential N-glycosylation sites	740:807	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	9	66	theme	targeted	1503:1510	arg1	manner					1512:1517	a targeted manner	1501:1517	a targeted manner	1501:1517	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	9	67	theme	colorectal	1583:1592	arg1	cancer					1594:1599	colorectal cancer progression and recurrence	1583:1626	cancer	1594:1599	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	9	68	dep	pave	1524:1527	arg1	investigated					1485:1496	investigated	1485:1496	further investigated in a targeted manner	1477:1517	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	2	69	theme	solid	407:411	arg1	tumors					413:418	many solid tumors	402:418	many solid tumors	402:418	CEA is often overexpressed and released by many solid tumors, including colorectal carcinomas.
33560857	2	69	theme	solid	407:411	arg1	carcinomas					442:451	colorectal carcinomas	431:451	colorectal carcinomas	431:451	CEA is often overexpressed and released by many solid tumors, including colorectal carcinomas.
33560857	0	70	theme	N-Linked	14:21	arg1	Analysis					37:44	Site-Specific N-Linked Glycosylation Analysis	0:44	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.	0:144	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	8	71	located	found	1301:1305	arg1	regard					1395:1400	regard	1395:1400	regard to branching, bisection, sialylation, and fucosylation	1395:1455	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	8	71	located	found	1301:1305	arg1	sites					1334:1338	certain N-glycosylation sites	1310:1338	certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor	1310:1390	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	8	71	located	found	1301:1305	arg2	differences					1284:1294	notable differences	1276:1294	notable differences	1276:1294	Moreover, notable differences were found on certain N-glycosylation sites between primary adenocarcinoma and metastatic tumor in regard to branching, bisection, sialylation, and fucosylation.
33560857	6	72	theme	unique	1102:1107	arg1	compositions					1118:1129	128 unique N-glycan compositions	1098:1129	128 unique N-glycan compositions	1098:1129	In total, 893 different N-glycopeptides and 128 unique N-glycan compositions were identified.
33560857	7	73	gly	N-glycosylation	1243:1257	arg2	sites					1259:1263	between (macro) individual N-glycosylation sites	1216:1263	between (macro) individual N-glycosylation sites	1216:1263	Overall, a great heterogeneity was found both within (micro) and in between (macro) individual N-glycosylation sites.
33560857	1	74	theme	molecular	304:312	arg1	mass					314:317	its molecular mass	300:317	its molecular mass	300:317	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	9	75	theme	recurrence	1617:1626	arg1	monitoring					1569:1578	monitoring	1569:1578	monitoring	1569:1578	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	9	75	theme	recurrence	1617:1626	arg1	diagnostics					1553:1563	improved diagnostics	1544:1563	improved diagnostics	1544:1563	Those features, if further investigated in a targeted manner, may pave the way toward improved diagnostics and monitoring of colorectal cancer progression and recurrence.
33560857	5	76	with	approach	898:905	arg1	trypsin					938:944	trypsin	938:944	trypsin	938:944	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	5	76	with	approach	898:905	arg1	Glu-C					962:966	endoproteinase Glu-C	947:966	endoproteinase Glu-C	947:966	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	5	76	with	approach	898:905	arg1	enzymes					921:927	specific enzymes	912:927	specific enzymes	912:927	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	5	76	with	approach	898:905	arg1	enzyme					989:994	the nonspecific enzyme	973:994	the nonspecific enzyme	973:994	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33560857	1	77	contain	bears	224:228	arg2	amount					241:246	an extreme amount	230:246	an extreme amount of N-linked glycosylation	230:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	77	contain	bears	224:228	arg1	CEA					219:221	CEA	219:221	CEA	219:221	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	77	contain	bears	224:228	arg2	glycosylation					260:272	N-linked glycosylation	251:272	N-linked glycosylation	251:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	77	contain	bears	224:228	arg1	antigen					210:216	human carcinoembryonic antigen	187:216	human carcinoembryonic antigen (CEA)	187:222	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	4	78	theme	potential	777:785	arg1	sites					803:807	21 out of 28 potential N-glycosylation sites	764:807	21 out of 28 potential N-glycosylation sites	764:807	The present study investigated CEA samples purified from human colon carcinoma and human liver metastases and enabled the characterization of 21 out of 28 potential N-glycosylation sites with respect to their occupancy.
33560857	2	79	theme	colorectal	431:440	arg1	carcinomas					442:451	colorectal carcinomas	431:451	colorectal carcinomas	431:451	CEA is often overexpressed and released by many solid tumors, including colorectal carcinomas.
33560857	0	80	theme	Human	49:53	arg1	Antigen					72:78	Human Carcinoembryonic Antigen	49:78	Human Carcinoembryonic Antigen	49:78	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	6	81	theme	different	1068:1076	arg1	N-glycopeptides					1078:1092	893 different N-glycopeptides	1064:1092	893 different N-glycopeptides	1064:1092	In total, 893 different N-glycopeptides and 128 unique N-glycan compositions were identified.
33560857	7	82	theme	between	1216:1222	arg1	sites					1259:1263	between (macro) individual N-glycosylation sites	1216:1263	between (macro) individual N-glycosylation sites	1216:1263	Overall, a great heterogeneity was found both within (micro) and in between (macro) individual N-glycosylation sites.
33560857	0	83	theme	Antigen	72:78	arg1	Analysis					37:44	Site-Specific N-Linked Glycosylation Analysis	0:44	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.	0:144	Site-Specific N-Linked Glycosylation Analysis of Human Carcinoembryonic Antigen by Sheathless Capillary Electrophoresis-Tandem Mass Spectrometry.
33560857	3	84	theme	sugar	514:518	arg1	content					520:526	sugar content	514:526	sugar content	514:526	CEA displays an impressive heterogeneity and variability in sugar content; however, site-specific distribution of carbohydrate structures has not been reported so far.
33560857	1	85	theme	glycosylation	260:272	arg1	amount					241:246	an extreme amount	230:246	an extreme amount of N-linked glycosylation	230:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	1	85	theme	glycosylation	260:272	arg1	glycosylation					260:272	N-linked glycosylation	251:272	N-linked glycosylation	251:272	With 28 potential N-glycosylation sites, human carcinoembryonic antigen (CEA) bears an extreme amount of N-linked glycosylation, and approximately 60% of its molecular mass can be attributed to its carbohydrates.
33560857	5	86	theme	sheathless	1033:1042	arg1	CE-MS/MS					1044:1051	sheathless CE-MS/MS	1033:1051	sheathless CE-MS/MS	1033:1051	The coverage was achieved by a multienzymatic digestion approach with specific enzymes, such as trypsin, endoproteinase Glu-C, and the nonspecific enzyme, Pronase, followed by analysis using sheathless CE-MS/MS.
33764747	0	0	from	Pathways	21:28	arg1	Actinobacteria					56:69	Gut- and Soil-Dwelling Actinobacteria	33:69	Gut- and Soil-Dwelling Actinobacteria	33:69	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria Share Common Core Genes.
33764747	5	1	theme	gut	896:898	arg1	bacterium					900:908	the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18)	892:998	the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18)	892:998	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	9	2	theme	core	1559:1562	arg1	structures					1564:1573	N-glycan core structures	1550:1573	N-glycan core structures	1550:1573	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	0	3	theme	Core	84:87	arg1	Genes					89:93	Common Core Genes	77:93	Common Core Genes	77:93	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria Share Common Core Genes.
33764747	1	4	located	found	150:154	arg1	archaea					179:185	archaea	179:185	archaea	179:185	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	1	4	located	found	150:154	arg1	eukaryotes					164:173	eukaryotes	164:173	eukaryotes	164:173	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	1	4	located	found	150:154	arg2	N-Glycosylation					96:110	N-Glycosylation	96:110	N-Glycosylation	96:110	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	1	4	located	found	150:154	arg2	modification					137:148	a fundamental protein modification	115:148	a fundamental protein modification found in both eukaryotes and archaea	115:185	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	2	5	theme	evasion	369:375	arg1	acquisition					353:363	nutrient acquisition	344:363	nutrient acquisition	344:363	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	5	theme	evasion	369:375	arg1	functions					323:331	functions	323:331	functions	323:331	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	5	theme	evasion	369:375	arg1	evasion					369:375	evasion	369:375	evasion of the immune system	369:396	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	5	theme	evasion	369:375	arg1	variety					312:318	a variety	310:318	a variety of functions, including nutrient acquisition and evasion of the immune system	310:396	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	8	6	theme	full	1359:1362	arg1	activity					1371:1378	full enzyme activity	1359:1378	full enzyme activity	1359:1378	Although this C-terminal cap is not widely distributed throughout the GH5_18 family, it is important for full enzyme activity.
33764747	7	7	theme	active	1195:1200	arg1	absent					1234:1239	absent	1234:1239	absent	1234:1239	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	7	theme	active	1195:1200	arg1	cap					1207:1209	a C-terminal active site cap	1182:1209	a C-terminal active site cap present in BlGH5_18	1182:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	9	8	located	found	1426:1430	arg1	loci					1476:1479	Gram-positive polysaccharide utilization loci	1435:1479	Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures	1435:1573	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	9	8	located	found	1426:1430	arg2	enzymes					1414:1420	GH5_18 enzymes	1407:1420	GH5_18 enzymes	1407:1420	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	5	9	theme	core	1021:1024	arg1	disaccharide					1040:1051	the core Manβ1-4GlcNAc disaccharide	1017:1051	the core Manβ1-4GlcNAc disaccharide	1017:1051	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	10	theme	bacterium	957:965	arg1	cattleya					980:987	the soil bacterium Streptomyces cattleya	948:987	the soil bacterium Streptomyces cattleya	948:987	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	11	theme	soil	952:955	arg1	bacterium					957:965	the soil bacterium	948:965	the soil bacterium Streptomyces cattleya	948:987	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	4	12	theme	structural	591:600	arg1	details					602:608	the structural details	587:608	the structural details	587:608	Thus, some of the structural details have yet to be characterized, and little is known about their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci.
33764747	7	13	theme	site	1202:1205	arg1	absent					1234:1239	absent	1234:1239	absent	1234:1239	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	13	theme	site	1202:1205	arg1	cap					1207:1209	a C-terminal active site cap	1182:1209	a C-terminal active site cap present in BlGH5_18	1182:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	6	14	theme	subsite	1153:1159	arg1	picture					1135:1141	a more complete picture	1119:1141	a more complete picture of the -1 subsite	1119:1159	Structures of these enzymes in complex with Manβ1-4GlcNAc reveal a more complete picture of the -1 subsite.
33764747	4	15	theme	full	672:675	arg1	distribution					677:688	their full distribution	666:688	their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci	666:792	Thus, some of the structural details have yet to be characterized, and little is known about their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci.
33764747	4	16	theme	utilization	777:787	arg1	loci					789:792	potential Gram-positive polysaccharide utilization loci	738:792	potential Gram-positive polysaccharide utilization loci	738:792	Thus, some of the structural details have yet to be characterized, and little is known about their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci.
33764747	5	17	theme	GH5_18	858:863	arg1	Family					834:839	Family 5	834:841	Family 5	834:841	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	17	theme	GH5_18	858:863	arg1	hydrolases					876:885	Subfamily 18 (GH5_18) glycoside hydrolases	844:885	Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18)	844:998	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	18	theme	Subfamily	844:852	arg1	Family					834:839	Family 5	834:841	Family 5	834:841	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	18	theme	Subfamily	844:852	arg1	hydrolases					876:885	Subfamily 18 (GH5_18) glycoside hydrolases	844:885	Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18)	844:998	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	6	19	theme	enzymes	1074:1080	arg1	Structures					1054:1063	Structures	1054:1063	Structures of these enzymes in complex with Manβ1-4GlcNAc	1054:1110	Structures of these enzymes in complex with Manβ1-4GlcNAc reveal a more complete picture of the -1 subsite.
33764747	3	20	theme	enzymes	440:446	arg1	enzymes					440:446	the enzymes	436:446	the enzymes responsible for N-glycan degradation	436:483	Although much is known about many of the enzymes responsible for N-glycan degradation, the enzymes involved in cleaving the N-glycan core have only recently been discovered.
33764747	3	20	theme	enzymes	440:446	arg1	many					428:431	many	428:431	many	428:431	Although much is known about many of the enzymes responsible for N-glycan degradation, the enzymes involved in cleaving the N-glycan core have only recently been discovered.
33764747	5	21	theme	crystal	811:817	arg1	structures					819:828	crystal structures	811:828	crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide	811:1051	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	3	22	theme	responsible	448:458	arg1	enzymes					440:446	the enzymes	436:446	the enzymes responsible for N-glycan degradation	436:483	Although much is known about many of the enzymes responsible for N-glycan degradation, the enzymes involved in cleaving the N-glycan core have only recently been discovered.
33764747	0	23	theme	Degradation	9:19	arg1	Pathways					21:28	N-Glycan Degradation Pathways	0:28	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria	0:69	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria Share Common Core Genes.
33764747	7	24	theme	present	1211:1217	arg1	absent					1234:1239	absent	1234:1239	absent	1234:1239	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	24	theme	present	1211:1217	arg1	cap					1207:1209	a C-terminal active site cap	1182:1209	a C-terminal active site cap present in BlGH5_18	1182:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	4	25	theme	potential	738:746	arg1	loci					789:792	potential Gram-positive polysaccharide utilization loci	738:792	potential Gram-positive polysaccharide utilization loci	738:792	Thus, some of the structural details have yet to be characterized, and little is known about their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci.
33764747	5	26	theme	glycoside	866:874	arg1	Family					834:839	Family 5	834:841	Family 5	834:841	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	26	theme	glycoside	866:874	arg1	hydrolases					876:885	Subfamily 18 (GH5_18) glycoside hydrolases	844:885	Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18)	844:998	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	0	27	theme	N-Glycan	0:7	arg1	Pathways					21:28	N-Glycan Degradation Pathways	0:28	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria	0:69	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria Share Common Core Genes.
33764747	9	28	theme	N-glycan	1550:1557	arg1	structures					1564:1573	N-glycan core structures	1550:1573	N-glycan core structures	1550:1573	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	2	29	theme	functions	323:331	arg1	acquisition					353:363	nutrient acquisition	344:363	nutrient acquisition	344:363	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	29	theme	functions	323:331	arg1	functions					323:331	functions	323:331	functions	323:331	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	29	theme	functions	323:331	arg1	evasion					369:375	evasion	369:375	evasion of the immune system	369:396	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	29	theme	functions	323:331	arg1	variety					312:318	a variety	310:318	a variety of functions, including nutrient acquisition and evasion of the immune system	310:396	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	30	theme	system	391:396	arg1	acquisition					353:363	nutrient acquisition	344:363	nutrient acquisition	344:363	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	30	theme	system	391:396	arg1	functions					323:331	functions	323:331	functions	323:331	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	2	30	theme	system	391:396	arg1	evasion					369:375	evasion	369:375	evasion of the immune system	369:396	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	9	31	theme	utilization	1464:1474	arg1	loci					1476:1479	Gram-positive polysaccharide utilization loci	1435:1479	Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures	1435:1573	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	6	32	from	Structures	1054:1063	arg1	complex					1085:1091	complex	1085:1091	complex with Manβ1-4GlcNAc	1085:1110	Structures of these enzymes in complex with Manβ1-4GlcNAc reveal a more complete picture of the -1 subsite.
33764747	4	33	theme	polysaccharide	762:775	arg1	loci					789:792	potential Gram-positive polysaccharide utilization loci	738:792	potential Gram-positive polysaccharide utilization loci	738:792	Thus, some of the structural details have yet to be characterized, and little is known about their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci.
33764747	9	34	theme	Gram-positive	1435:1447	arg1	loci					1476:1479	Gram-positive polysaccharide utilization loci	1435:1479	Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures	1435:1573	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	5	35	dep	bacterium	900:908	arg1	longum					926:931	Bifidobacterium longum	910:931	Bifidobacterium longum (BlGH5_18)	910:942	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	35	dep	bacterium	900:908	arg1	ScGH5_18					990:997	ScGH5_18	990:997	ScGH5_18	990:997	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	35	dep	bacterium	900:908	arg1	cattleya					980:987	the soil bacterium Streptomyces cattleya	948:987	the soil bacterium Streptomyces cattleya	948:987	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	35	dep	bacterium	900:908	arg1	BlGH5_18					934:941	BlGH5_18	934:941	BlGH5_18	934:941	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	4	36	theme	Gram-positive	748:760	arg1	loci					789:792	potential Gram-positive polysaccharide utilization loci	738:792	potential Gram-positive polysaccharide utilization loci	738:792	Thus, some of the structural details have yet to be characterized, and little is known about their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci.
33764747	7	37	from	absent	1234:1239	arg1	ScGH5_18					1244:1251	ScGH5_18	1244:1251	ScGH5_18	1244:1251	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	2	38	theme	immune	384:389	arg1	system					391:396	the immune system	380:396	the immune system	380:396	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	4	39	theme	bacterial	696:704	arg1	strains					706:712	bacterial strains	696:712	bacterial strains	696:712	Thus, some of the structural details have yet to be characterized, and little is known about their full distribution among bacterial strains and specifically within potential Gram-positive polysaccharide utilization loci.
33764747	9	40	theme	polysaccharide	1449:1462	arg1	loci					1476:1479	Gram-positive polysaccharide utilization loci	1435:1479	Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures	1435:1573	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	8	41	theme	C-terminal	1268:1277	arg1	cap					1279:1281	this C-terminal cap	1263:1281	this C-terminal cap	1263:1281	Although this C-terminal cap is not widely distributed throughout the GH5_18 family, it is important for full enzyme activity.
33764747	0	42	theme	Gut-	33:36	arg1	Actinobacteria					56:69	Gut- and Soil-Dwelling Actinobacteria	33:69	Gut- and Soil-Dwelling Actinobacteria	33:69	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria Share Common Core Genes.
33764747	6	43	with	complex	1085:1091	arg1	Manβ1-4GlcNAc					1098:1110	Manβ1-4GlcNAc	1098:1110	Manβ1-4GlcNAc	1098:1110	Structures of these enzymes in complex with Manβ1-4GlcNAc reveal a more complete picture of the -1 subsite.
33764747	3	44	theme	N-glycan	464:471	arg1	degradation					473:483	N-glycan degradation	464:483	N-glycan degradation	464:483	Although much is known about many of the enzymes responsible for N-glycan degradation, the enzymes involved in cleaving the N-glycan core have only recently been discovered.
33764747	2	45	theme	pathogenic	234:243	arg1	bacteria					245:252	many commensal and pathogenic bacteria	215:252	many commensal and pathogenic bacteria	215:252	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	9	46	theme	GH5_18	1407:1412	arg1	enzymes					1414:1420	GH5_18 enzymes	1407:1420	GH5_18 enzymes	1407:1420	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	1	47	theme	fundamental	117:127	arg1	modification					137:148	a fundamental protein modification	115:148	a fundamental protein modification found in both eukaryotes and archaea	115:185	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	1	47	theme	fundamental	117:127	arg1	N-Glycosylation					96:110	N-Glycosylation	96:110	N-Glycosylation	96:110	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	0	48	theme	Soil-Dwelling	42:54	arg1	Actinobacteria					56:69	Gut- and Soil-Dwelling Actinobacteria	33:69	Gut- and Soil-Dwelling Actinobacteria	33:69	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria Share Common Core Genes.
33764747	7	49	theme	C-terminal	1184:1193	arg1	absent					1234:1239	absent	1234:1239	absent	1234:1239	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	49	theme	C-terminal	1184:1193	arg1	cap					1207:1209	a C-terminal active site cap	1182:1209	a C-terminal active site cap present in BlGH5_18	1182:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	2	50	theme	commensal	220:228	arg1	bacteria					245:252	many commensal and pathogenic bacteria	215:252	many commensal and pathogenic bacteria	215:252	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	5	51	theme	Manβ1-4GlcNAc	1026:1038	arg1	disaccharide					1040:1051	the core Manβ1-4GlcNAc disaccharide	1017:1051	the core Manβ1-4GlcNAc disaccharide	1017:1051	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	1	52	theme	protein	129:135	arg1	modification					137:148	a fundamental protein modification	115:148	a fundamental protein modification found in both eukaryotes and archaea	115:185	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	1	52	theme	protein	129:135	arg1	N-Glycosylation					96:110	N-Glycosylation	96:110	N-Glycosylation	96:110	N-Glycosylation is a fundamental protein modification found in both eukaryotes and archaea.
33764747	2	53	theme	many	215:218	arg1	bacteria					245:252	many commensal and pathogenic bacteria	215:252	many commensal and pathogenic bacteria	215:252	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	5	54	from	bacterium	900:908	arg1	Family					834:839	Family 5	834:841	Family 5	834:841	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	5	54	from	bacterium	900:908	arg1	hydrolases					876:885	Subfamily 18 (GH5_18) glycoside hydrolases	844:885	Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18)	844:998	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	2	55	theme	nutrient	344:351	arg1	acquisition					353:363	nutrient acquisition	344:363	nutrient acquisition	344:363	Despite lacking N-glycans, many commensal and pathogenic bacteria have developed mechanisms to degrade these isoforms for a variety of functions, including nutrient acquisition and evasion of the immune system.
33764747	8	56	theme	enzyme	1364:1369	arg1	activity					1371:1378	full enzyme activity	1359:1378	full enzyme activity	1359:1378	Although this C-terminal cap is not widely distributed throughout the GH5_18 family, it is important for full enzyme activity.
33764747	9	57	theme	common	1492:1497	arg1	genes					1499:1503	common genes	1492:1503	common genes	1492:1503	In addition, we show that GH5_18 enzymes are found in Gram-positive polysaccharide utilization loci that share common genes, likely dedicated to importing and degrading N-glycan core structures.
33764747	8	58	theme	GH5_18	1324:1329	arg1	family					1331:1336	the GH5_18 family	1320:1336	the GH5_18 family	1320:1336	Although this C-terminal cap is not widely distributed throughout the GH5_18 family, it is important for full enzyme activity.
33764747	6	59	theme	complete	1126:1133	arg1	picture					1135:1141	a more complete picture	1119:1141	a more complete picture of the -1 subsite	1119:1159	Structures of these enzymes in complex with Manβ1-4GlcNAc reveal a more complete picture of the -1 subsite.
33764747	0	60	theme	Common	77:82	arg1	Genes					89:93	Common Core Genes	77:93	Common Core Genes	77:93	N-Glycan Degradation Pathways in Gut- and Soil-Dwelling Actinobacteria Share Common Core Genes.
33764747	7	61	from	BlGH5_18	1222:1229	arg1	present					1211:1217	present	1211:1217	present	1211:1217	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	3	62	theme	N-glycan	523:530	arg1	core					532:535	the N-glycan core	519:535	the N-glycan core	519:535	Although much is known about many of the enzymes responsible for N-glycan degradation, the enzymes involved in cleaving the N-glycan core have only recently been discovered.
33764747	7	63	from	ScGH5_18	1244:1251	arg1	absent					1234:1239	absent	1234:1239	absent	1234:1239	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	63	from	ScGH5_18	1244:1251	arg1	cap					1207:1209	a C-terminal active site cap	1182:1209	a C-terminal active site cap present in BlGH5_18	1182:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	5	64	theme	Streptomyces	967:978	arg1	cattleya					980:987	the soil bacterium Streptomyces cattleya	948:987	the soil bacterium Streptomyces cattleya	948:987	Here, we report crystal structures for Family 5, Subfamily 18 (GH5_18) glycoside hydrolases from the gut bacterium Bifidobacterium longum (BlGH5_18) and the soil bacterium Streptomyces cattleya (ScGH5_18), which hydrolyze the core Manβ1-4GlcNAc disaccharide.
33764747	7	65	attach	present	1211:1217	arg2	cap					1207:1209	a C-terminal active site cap	1182:1209	a C-terminal active site cap present in BlGH5_18	1182:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	65	attach	present	1211:1217	arg2	absent					1234:1239	absent	1234:1239	absent	1234:1239	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	65	attach	present	1211:1217	arg1	BlGH5_18					1222:1229	BlGH5_18	1222:1229	BlGH5_18	1222:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33764747	7	66	from	present	1211:1217	arg1	BlGH5_18					1222:1229	BlGH5_18	1222:1229	BlGH5_18	1222:1229	They also show that a C-terminal active site cap present in BlGH5_18 is absent in ScGH5_18.
33659899	0	0	theme	mammalian	82:90	arg1	cells					92:96	mammalian cells	82:96	mammalian cells	82:96	Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.
33659899	3	1	theme	metabolites	549:559	arg1	isolation					419:427	isolation	419:427	isolation	419:427	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	1	theme	metabolites	549:559	arg1	determination					441:453	structural determination	430:453	structural determination	430:453	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	1	theme	metabolites	549:559	arg1	quantification					460:473	quantification	460:473	quantification	460:473	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	1	2	theme	endoplasmic	179:189	arg1	reticulum					191:199	the endoplasmic reticulum	175:199	the endoplasmic reticulum of eukaryotic cells	175:219	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	5	3	theme	protocol	791:798	arg1	execution					773:781	execution	773:781	execution	773:781	For complete details on the use and execution of this protocol, please refer to Harada et al. (2013), Harada et al. (2020), and Nakajima et al. (2013).
33659899	5	3	theme	protocol	791:798	arg1	use					765:767	the use	761:767	the use	761:767	For complete details on the use and execution of this protocol, please refer to Harada et al. (2013), Harada et al. (2020), and Nakajima et al. (2013).
33659899	3	4	link	dolichol-linked	499:513	arg1	oligosaccharides					587:602	phosphorylated oligosaccharides	572:602	phosphorylated oligosaccharides	572:602	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	4	link	dolichol-linked	499:513	arg1	sugars					619:624	nucleotide sugars	608:624	nucleotide sugars	608:624	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	4	link	dolichol-linked	499:513	arg1	oligosaccharides					515:530	dolichol-linked oligosaccharides	499:530	dolichol-linked oligosaccharides	499:530	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	5	theme	nucleotide	608:617	arg1	sugars					619:624	nucleotide sugars	608:624	nucleotide sugars	608:624	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	6	theme	non-radiolabeling	384:400	arg1	protocol					402:409	a non-radiolabeling protocol	382:409	a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars	382:624	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	7	dep	isolation	419:427	arg1	the					415:417	the	415:417	the	415:417	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	1	8	from	modification	159:170	arg1	reticulum					191:199	the endoplasmic reticulum	175:199	the endoplasmic reticulum of eukaryotic cells	175:219	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	2	9	from	flux	253:256	arg1	cells					285:289	eukaryotic cells	274:289	eukaryotic cells	274:289	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells has long been analyzed by metabolic labeling using radiolabeled sugars.
33659899	4	10	from	capturing	651:659	arg1	state					730:734	steady state	723:734	steady state	723:734	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	0	11	from	degradation	44:54	arg1	cells					92:96	mammalian cells	82:96	mammalian cells	82:96	Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.
33659899	4	12	theme	N-glycan	700:707	arg1	precursors					709:718	N-glycan precursors	700:718	N-glycan precursors	700:718	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	3	13	theme	N-glycan	478:485	arg1	oligosaccharides					587:602	phosphorylated oligosaccharides	572:602	phosphorylated oligosaccharides	572:602	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	13	theme	N-glycan	478:485	arg1	sugars					619:624	nucleotide sugars	608:624	nucleotide sugars	608:624	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	13	theme	N-glycan	478:485	arg1	precursors					487:496	N-glycan precursors	478:496	N-glycan precursors	478:496	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	0	14	from	biosynthesis	27:38	arg1	cells					92:96	mammalian cells	82:96	mammalian cells	82:96	Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.
33659899	2	15	theme	radiolabeled	342:353	arg1	sugars					355:360	radiolabeled sugars	342:360	radiolabeled sugars	342:360	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells has long been analyzed by metabolic labeling using radiolabeled sugars.
33659899	4	16	from	state	730:734	arg1	degradation					685:695	degradation	685:695	degradation	685:695	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	4	16	from	state	730:734	arg1	capturing					651:659	capturing	651:659	capturing of the biosynthesis and degradation of N-glycan precursors at steady state	651:734	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	4	16	from	state	730:734	arg1	biosynthesis					668:679	biosynthesis	668:679	biosynthesis	668:679	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	1	17	theme	eukaryotic	204:213	arg1	cells					215:219	eukaryotic cells	204:219	eukaryotic cells	204:219	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	1	18	theme	cells	215:219	arg1	reticulum					191:199	the endoplasmic reticulum	175:199	the endoplasmic reticulum of eukaryotic cells	175:219	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	5	19	dep	et al	824:828	arg1	et al					874:878	et al	874:878	et al	874:878	For complete details on the use and execution of this protocol, please refer to Harada et al. (2013), Harada et al. (2020), and Nakajima et al. (2013).
33659899	0	20	dep	biosynthesis	27:38	arg1	the					23:25	the	23:25	the	23:25	Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.
33659899	3	21	theme	dolichol-linked	499:513	arg1	oligosaccharides					587:602	phosphorylated oligosaccharides	572:602	phosphorylated oligosaccharides	572:602	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	21	theme	dolichol-linked	499:513	arg1	sugars					619:624	nucleotide sugars	608:624	nucleotide sugars	608:624	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	21	theme	dolichol-linked	499:513	arg1	oligosaccharides					515:530	dolichol-linked oligosaccharides	499:530	dolichol-linked oligosaccharides	499:530	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	2	22	theme	metabolic	317:325	arg1	labeling					327:334	metabolic labeling	317:334	metabolic labeling using radiolabeled sugars	317:360	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells has long been analyzed by metabolic labeling using radiolabeled sugars.
33659899	3	23	theme	oligosaccharides	515:530	arg1	isolation					419:427	isolation	419:427	isolation	419:427	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	23	theme	oligosaccharides	515:530	arg1	determination					441:453	structural determination	430:453	structural determination	430:453	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	23	theme	oligosaccharides	515:530	arg1	quantification					460:473	quantification	460:473	quantification	460:473	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	24	theme	related	541:547	arg1	oligosaccharides					587:602	phosphorylated oligosaccharides	572:602	phosphorylated oligosaccharides	572:602	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	24	theme	related	541:547	arg1	sugars					619:624	nucleotide sugars	608:624	nucleotide sugars	608:624	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	24	theme	related	541:547	arg1	metabolites					549:559	the related metabolites	537:559	the related metabolites	537:559	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	4	25	theme	steady	723:728	arg1	state					730:734	steady state	723:734	steady state	723:734	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	2	26	theme	N-glycans	261:269	arg1	flux					253:256	The biosynthetic and catabolic flux	222:256	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells	222:289	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells has long been analyzed by metabolic labeling using radiolabeled sugars.
33659899	3	27	theme	precursors	487:496	arg1	isolation					419:427	isolation	419:427	isolation	419:427	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	27	theme	precursors	487:496	arg1	determination					441:453	structural determination	430:453	structural determination	430:453	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	3	27	theme	precursors	487:496	arg1	quantification					460:473	quantification	460:473	quantification	460:473	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	5	28	from	details	750:756	arg1	execution					773:781	execution	773:781	execution	773:781	For complete details on the use and execution of this protocol, please refer to Harada et al. (2013), Harada et al. (2020), and Nakajima et al. (2013).
33659899	5	28	from	details	750:756	arg1	use					765:767	the use	761:767	the use	761:767	For complete details on the use and execution of this protocol, please refer to Harada et al. (2013), Harada et al. (2020), and Nakajima et al. (2013).
33659899	3	29	theme	structural	430:439	arg1	determination					441:453	structural determination	430:453	structural determination	430:453	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	2	30	theme	catabolic	243:251	arg1	flux					253:256	The biosynthetic and catabolic flux	222:256	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells	222:289	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells has long been analyzed by metabolic labeling using radiolabeled sugars.
33659899	1	31	theme	fundamental	120:130	arg1	N-glycosylation					99:113	N-glycosylation	99:113	N-glycosylation	99:113	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	1	31	theme	fundamental	120:130	arg1	modification					159:170	a fundamental post-translational protein modification	118:170	a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells	118:219	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	2	32	theme	biosynthetic	226:237	arg1	flux					253:256	The biosynthetic and catabolic flux	222:256	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells	222:289	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells has long been analyzed by metabolic labeling using radiolabeled sugars.
33659899	1	33	theme	post-translational	132:149	arg1	N-glycosylation					99:113	N-glycosylation	99:113	N-glycosylation	99:113	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	1	33	theme	post-translational	132:149	arg1	modification					159:170	a fundamental post-translational protein modification	118:170	a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells	118:219	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	1	34	theme	protein	151:157	arg1	N-glycosylation					99:113	N-glycosylation	99:113	N-glycosylation	99:113	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	1	34	theme	protein	151:157	arg1	modification					159:170	a fundamental post-translational protein modification	118:170	a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells	118:219	N-glycosylation is a fundamental post-translational protein modification in the endoplasmic reticulum of eukaryotic cells.
33659899	4	35	theme	biosynthesis	668:679	arg1	capturing					651:659	capturing	651:659	capturing of the biosynthesis and degradation of N-glycan precursors at steady state	651:734	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	0	36	theme	precursors	68:77	arg1	degradation					44:54	degradation	44:54	degradation	44:54	Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.
33659899	0	36	theme	precursors	68:77	arg1	biosynthesis					27:38	biosynthesis	27:38	biosynthesis	27:38	Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.
33659899	4	37	dep	biosynthesis	668:679	arg1	the					664:666	the	664:666	the	664:666	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	2	38	theme	eukaryotic	274:283	arg1	cells					285:289	eukaryotic cells	274:289	eukaryotic cells	274:289	The biosynthetic and catabolic flux of N-glycans in eukaryotic cells has long been analyzed by metabolic labeling using radiolabeled sugars.
33659899	4	39	theme	precursors	709:718	arg1	degradation					685:695	degradation	685:695	degradation	685:695	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	4	39	theme	precursors	709:718	arg1	biosynthesis					668:679	biosynthesis	668:679	biosynthesis	668:679	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
33659899	5	40	theme	complete	741:748	arg1	details					750:756	complete details	741:756	complete details on the use and execution of this protocol	741:798	For complete details on the use and execution of this protocol, please refer to Harada et al. (2013), Harada et al. (2020), and Nakajima et al. (2013).
33659899	0	41	theme	N-glycan	59:66	arg1	precursors					68:77	N-glycan precursors	59:77	N-glycan precursors	59:77	Protocol for analyzing the biosynthesis and degradation of N-glycan precursors in mammalian cells.
33659899	3	42	theme	phosphorylated	572:585	arg1	oligosaccharides					587:602	phosphorylated oligosaccharides	572:602	phosphorylated oligosaccharides	572:602	Here, we introduce a non-radiolabeling protocol for the isolation, structural determination, and quantification of N-glycan precursors, dolichol-linked oligosaccharides, and the related metabolites, including phosphorylated oligosaccharides and nucleotide sugars.
33659899	4	43	theme	degradation	685:695	arg1	capturing					651:659	capturing	651:659	capturing of the biosynthesis and degradation of N-glycan precursors at steady state	651:734	Our protocol allows for capturing of the biosynthesis and degradation of N-glycan precursors at steady state.
34309358	0	0	theme	Sialyl	83:88	arg1	T-Antigen					90:98	Intact Sialyl T-Antigen	76:98	Intact Sialyl T-Antigen	76:98	Discovery and Development of Promiscuous O-Glycan Hydrolases for Removal of Intact Sialyl T-Antigen.
34309358	1	1	theme	post-translational	158:175	arg1	O-glycosylation					112:126	Mucin-type O-glycosylation	101:126	Mucin-type O-glycosylation (O-glycosylation)	101:144	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	1	1	theme	post-translational	158:175	arg1	modification					177:188	a common post-translational modification	149:188	a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling	149:296	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	1	2	theme	intercellular	274:286	arg1	signaling					288:296	intercellular signaling	274:296	intercellular signaling	274:296	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	0	3	theme	Intact	76:81	arg1	T-Antigen					90:98	Intact Sialyl T-Antigen	76:98	Intact Sialyl T-Antigen	76:98	Discovery and Development of Promiscuous O-Glycan Hydrolases for Removal of Intact Sialyl T-Antigen.
34309358	4	4	theme	T-antigen	877:885	arg1	disaccharide					887:898	the T-antigen disaccharide	873:898	the T-antigen disaccharide	873:898	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	3	5	theme	protein	511:517	arg1	surfaces					519:526	protein surfaces	511:526	protein surfaces	511:526	In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing.
34309358	8	6	theme	proteins	1564:1571	arg1	number					1554:1559	a number	1552:1559	a number of proteins, tissues, and cells	1552:1591	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	4	7	theme	functional	581:590	arg1	screening					604:612	functional metagenomic screening	581:612	functional metagenomic screening of the human gut microbiome	581:640	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	7	8	theme	phylogenetic	1328:1339	arg1	profiling					1341:1349	phylogenetic profiling	1328:1349	phylogenetic profiling	1328:1349	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	3	9	theme	glycan	543:548	arg1	profiling					550:558	glycan profiling	543:558	glycan profiling	543:558	In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing.
34309358	4	10	from	GH101	699:703	arg1	hydrolases					671:680	endo-O-glycan hydrolases	657:680	endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide	657:898	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	0	11	theme	T-Antigen	90:98	arg1	Removal					65:71	Removal	65:71	Removal of Intact Sialyl T-Antigen	65:98	Discovery and Development of Promiscuous O-Glycan Hydrolases for Removal of Intact Sialyl T-Antigen.
34309358	9	12	theme	improved	1625:1632	arg1	methodologies					1634:1646	improved methodologies	1625:1646	improved methodologies for unraveling the glycan code	1625:1677	Access to this enzyme opens up improved methodologies for unraveling the glycan code.
34309358	5	13	theme	enzymes	1008:1014	arg1	analysis					981:988	phylogenetic profiling and analysis	954:988	analysis	981:988	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	5	13	theme	enzymes	1008:1014	arg1	profiling					967:975	phylogenetic profiling and analysis	954:988	profiling	967:975	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	3	14	theme	O-glycan	482:489	arg1	structures					491:500	O-glycan structures	482:500	O-glycan structures found on protein surfaces	482:526	In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing.
34309358	7	15	theme	rational	1246:1253	arg1	engineering					1263:1273	subsequent rational protein engineering	1235:1273	subsequent rational protein engineering	1235:1273	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	4	16	dep	trisaccharide	769:781	arg1	structure					806:814	a ubiquitous O-glycan structure	784:814	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	4	17	theme	O-glycan	797:804	arg1	structure					806:814	a ubiquitous O-glycan structure	784:814	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	4	18	theme	family	692:697	arg1	GH101					699:703	CAZy family GH101	687:703	CAZy family GH101	687:703	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	7	19	theme	sialyl	1403:1408	arg1	T-antigen					1410:1418	the intact sialyl T-antigen	1392:1418	the intact sialyl T-antigen	1392:1418	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	7	20	theme	protein	1255:1261	arg1	engineering					1263:1273	subsequent rational protein engineering	1235:1273	subsequent rational protein engineering	1235:1273	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	8	21	theme	cells	1587:1591	arg1	number					1554:1559	a number	1552:1559	a number of proteins, tissues, and cells	1552:1591	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	4	22	theme	metagenomic	592:602	arg1	screening					604:612	functional metagenomic screening	581:612	functional metagenomic screening of the human gut microbiome	581:640	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	4	23	from	trisaccharide	769:781	arg1	humans					819:824	humans	819:824	humans	819:824	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	4	24	theme	ubiquitous	786:795	arg1	structure					806:814	a ubiquitous O-glycan structure	784:814	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	6	25	theme	structural	1131:1140	arg1	analysis					1155:1162	structural and sequence analysis	1131:1162	analysis	1155:1162	Through structural and sequence analysis, we identified active site residues that modulate specificity.
34309358	7	26	theme	T-antigen	1410:1418	arg1	removal					1381:1387	substantial removal	1369:1387	substantial removal of the intact sialyl T-antigen from proteins	1369:1432	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	4	27	theme	sialyl	752:757	arg1	trisaccharide					769:781	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	5	28	from	differences	1033:1043	arg1	levels					1052:1057	the levels	1048:1057	the levels of this promiscuous activity between enzymes within the family	1048:1120	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	1	29	theme	distinct	203:210	arg1	properties					224:233	distinct biophysical properties	203:233	distinct biophysical properties	203:233	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	7	30	theme	subsequent	1235:1244	arg1	engineering					1263:1273	subsequent rational protein engineering	1235:1273	subsequent rational protein engineering	1235:1273	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	4	31	theme	intact	745:750	arg1	trisaccharide					769:781	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	1	32	theme	biophysical	212:222	arg1	properties					224:233	distinct biophysical properties	203:233	distinct biophysical properties	203:233	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	4	33	dep	activity	856:863	arg1	addition					830:837	addition	830:837	addition	830:837	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	5	34	theme	promiscuous	1067:1077	arg1	activity					1079:1086	this promiscuous activity	1062:1086	this promiscuous activity between enzymes within the family	1062:1120	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	5	35	theme	phylogenetic	954:965	arg1	profiling					967:975	phylogenetic profiling and analysis	954:988	profiling	967:975	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	2	36	theme	O-glycans	330:338	arg1	importance					316:325	the importance	312:325	the importance of O-glycans	312:338	Yet, despite the importance of O-glycans, relatively few tools exist for their analysis and modification.
34309358	3	37	theme	wide	468:471	arg1	range					473:477	the wide range	464:477	the wide range of O-glycan structures found on protein surfaces	464:526	In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing.
34309358	8	38	theme	tissues	1574:1580	arg1	number					1554:1559	a number	1552:1559	a number of proteins, tissues, and cells	1552:1591	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	4	39	theme	T-antigen	759:767	arg1	trisaccharide					769:781	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans)	741:825	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	0	40	theme	O-Glycan	41:48	arg1	Hydrolases					50:59	Promiscuous O-Glycan Hydrolases	29:59	Promiscuous O-Glycan Hydrolases	29:59	Discovery and Development of Promiscuous O-Glycan Hydrolases for Removal of Intact Sialyl T-Antigen.
34309358	7	41	from	proteins	1425:1432	arg1	removal					1381:1387	substantial removal	1369:1387	substantial removal of the intact sialyl T-antigen from proteins	1369:1432	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	9	42	dep	glycan	1667:1672	arg1	code					1674:1677	code	1674:1677	code	1674:1677	Access to this enzyme opens up improved methodologies for unraveling the glycan code.
34309358	8	43	theme	sialyl	1470:1475	arg1	mutant					1497:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	8	43	theme	sialyl	1470:1475	arg1	Q868G					1513:1517	Q868G	1513:1517	Q868G	1513:1517	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	4	44	theme	CAZy	687:690	arg1	GH101					699:703	CAZy family GH101	687:703	CAZy family GH101	687:703	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	4	45	theme	endo-O-glycan	657:669	arg1	hydrolases					671:680	endo-O-glycan hydrolases	657:680	endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide	657:898	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	0	46	theme	Promiscuous	29:39	arg1	Hydrolases					50:59	Promiscuous O-Glycan Hydrolases	29:59	Promiscuous O-Glycan Hydrolases	29:59	Discovery and Development of Promiscuous O-Glycan Hydrolases for Removal of Intact Sialyl T-Antigen.
34309358	8	47	theme	best	1465:1468	arg1	mutant					1497:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	8	47	theme	best	1465:1468	arg1	Q868G					1513:1517	Q868G	1513:1517	Q868G	1513:1517	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	7	48	theme	substantial	1369:1379	arg1	removal					1381:1387	substantial removal	1369:1387	substantial removal of the intact sialyl T-antigen from proteins	1369:1432	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	8	49	theme	hydrolase	1487:1495	arg1	mutant					1497:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	8	49	theme	hydrolase	1487:1495	arg1	Q868G					1513:1517	Q868G	1513:1517	Q868G	1513:1517	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	3	50	theme	structures	491:500	arg1	range					473:477	the wide range	464:477	the wide range of O-glycan structures found on protein surfaces	464:526	In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing.
34309358	0	51	theme	Hydrolases	50:59	arg1	Development					14:24	Development	14:24	Development	14:24	Discovery and Development of Promiscuous O-Glycan Hydrolases for Removal of Intact Sialyl T-Antigen.
34309358	0	51	theme	Hydrolases	50:59	arg1	Discovery					0:8	Discovery	0:8	Discovery	0:8	Discovery and Development of Promiscuous O-Glycan Hydrolases for Removal of Intact Sialyl T-Antigen.
34309358	7	52	theme	intact	1396:1401	arg1	T-antigen					1410:1418	the intact sialyl T-antigen	1392:1418	the intact sialyl T-antigen	1392:1418	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	5	53	theme	activity	1079:1086	arg1	levels					1052:1057	the levels	1048:1057	the levels of this promiscuous activity between enzymes within the family	1048:1120	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	4	54	theme	primary	848:854	arg1	activity					856:863	their primary activity	842:863	their primary activity against the T-antigen disaccharide	842:898	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	5	55	theme	large	1027:1031	arg1	differences					1033:1043	large differences	1027:1043	large differences in the levels of this promiscuous activity between enzymes within the family	1027:1120	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	1	56	theme	Mucin-type	101:110	arg1	modification					177:188	a common post-translational modification	149:188	a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling	149:296	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	1	56	theme	Mucin-type	101:110	arg1	O-glycosylation					129:143	O-glycosylation	129:143	O-glycosylation	129:143	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	1	56	theme	Mucin-type	101:110	arg1	O-glycosylation					112:126	Mucin-type O-glycosylation	101:126	Mucin-type O-glycosylation (O-glycosylation)	101:144	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	4	57	theme	human	621:625	arg1	microbiome					631:640	the human gut microbiome	617:640	the human gut microbiome	617:640	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	5	58	theme	sequence	931:938	arg1	space					940:944	this sequence space	926:944	this sequence space	926:944	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	5	59	theme	representative	993:1006	arg1	enzymes					1008:1014	representative enzymes	993:1014	representative enzymes	993:1014	We then further explored this sequence space through phylogenetic profiling and analysis of representative enzymes, revealing large differences in the levels of this promiscuous activity between enzymes within the family.
34309358	3	60	located	found	502:506	arg1	surfaces					519:526	protein surfaces	511:526	protein surfaces	511:526	In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing.
34309358	3	60	located	found	502:506	arg2	structures					491:500	O-glycan structures	482:500	O-glycan structures found on protein surfaces	482:526	In particular, there is a need for enzymes that can cleave the wide range of O-glycan structures found on protein surfaces, to facilitate glycan profiling and editing.
34309358	2	61	theme	few	352:354	arg1	tools					356:360	relatively few tools	341:360	relatively few tools	341:360	Yet, despite the importance of O-glycans, relatively few tools exist for their analysis and modification.
34309358	6	62	theme	active	1179:1184	arg1	residues					1191:1198	active site residues	1179:1198	active site residues that modulate specificity	1179:1224	Through structural and sequence analysis, we identified active site residues that modulate specificity.
34309358	1	63	theme	crucial	257:263	arg1	roles					265:269	crucial roles	257:269	crucial roles	257:269	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	6	64	theme	sequence	1146:1153	arg1	analysis					1155:1162	structural and sequence analysis	1131:1162	analysis	1155:1162	Through structural and sequence analysis, we identified active site residues that modulate specificity.
34309358	7	65	theme	enzyme	1307:1312	arg1	activity					1292:1299	the activity	1288:1299	the activity of an enzyme identified by phylogenetic profiling	1288:1349	Through subsequent rational protein engineering, we improved the activity of an enzyme identified by phylogenetic profiling sufficiently that substantial removal of the intact sialyl T-antigen from proteins could be readily achieved.
34309358	4	66	theme	microbiome	631:640	arg1	screening					604:612	functional metagenomic screening	581:612	functional metagenomic screening of the human gut microbiome	581:640	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
34309358	6	67	theme	site	1186:1189	arg1	residues					1191:1198	active site residues	1179:1198	active site residues that modulate specificity	1179:1224	Through structural and sequence analysis, we identified active site residues that modulate specificity.
34309358	1	68	theme	common	151:156	arg1	O-glycosylation					112:126	Mucin-type O-glycosylation	101:126	Mucin-type O-glycosylation (O-glycosylation)	101:144	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	1	68	theme	common	151:156	arg1	modification					177:188	a common post-translational modification	149:188	a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling	149:296	Mucin-type O-glycosylation (O-glycosylation) is a common post-translational modification that confers distinct biophysical properties to proteins and plays crucial roles in intercellular signaling.
34309358	8	69	theme	T-antigen	1477:1485	arg1	mutant					1497:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant	1461:1502	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	8	69	theme	T-antigen	1477:1485	arg1	Q868G					1513:1517	Q868G	1513:1517	Q868G	1513:1517	Our best sialyl T-antigen hydrolase mutant, SpGH101 Q868G, is further shown to function on a number of proteins, tissues, and cells.
34309358	4	70	theme	gut	627:629	arg1	microbiome					631:640	the human gut microbiome	617:640	the human gut microbiome	617:640	Through functional metagenomic screening of the human gut microbiome, we discovered endo-O-glycan hydrolases from CAZy family GH101 that are capable of slowly cleaving the intact sialyl T-antigen trisaccharide (a ubiquitous O-glycan structure in humans) in addition to their primary activity against the T-antigen disaccharide.
33205023	4	0	theme	glycosylation	869:881	arg1	heterogeneity					883:895	site-specific glycosylation heterogeneity	855:895	site-specific glycosylation heterogeneity	855:895	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	1	1	theme	virus-cell	145:154	arg1	entry					156:160	impact virus-cell entry	138:160	impact virus-cell entry	138:160	HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion.
33205023	5	2	theme	Molecular-dynamic	960:976	arg1	simulations					978:988	Molecular-dynamic simulations	960:988	Molecular-dynamic simulations	960:988	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	4	3	theme	several	793:799	arg1	antibodies					831:840	several glycan-dependent neutralizing antibodies	793:840	several glycan-dependent neutralizing antibodies	793:840	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	4	4	theme	site-specific	855:867	arg1	heterogeneity					883:895	site-specific glycosylation heterogeneity	855:895	site-specific glycosylation heterogeneity	855:895	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	5	5	theme	specific	1039:1046	arg1	positions					1064:1072	specific oligosaccharide positions	1039:1072	specific oligosaccharide positions	1039:1072	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	4	6	theme	neutralizing	818:829	arg1	antibodies					831:840	several glycan-dependent neutralizing antibodies	793:840	several glycan-dependent neutralizing antibodies	793:840	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	6	7	theme	Env-glycan	1236:1245	arg1	processing					1204:1213	processing	1204:1213	processing	1204:1213	This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
33205023	6	7	theme	Env-glycan	1236:1245	arg1	function					1220:1227	function	1220:1227	function	1220:1227	This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
33205023	6	7	theme	Env-glycan	1236:1245	arg1	dynamics					1194:1201	molecular dynamics	1184:1201	molecular dynamics	1184:1201	This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
33205023	4	8	theme	Env	732:734	arg1	binding					736:742	Env binding	732:742	Env binding to the CD4 receptor	732:762	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	3	9	theme	same	340:343	arg1	donor					345:349	the same donor	336:349	the same donor	336:349	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	10	from	donor	345:349	arg1	analysis					302:309	analysis	302:309	analysis of two Env variants from the same donor	302:349	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	10	from	donor	345:349	arg1	variants					322:329	two Env variants	314:329	two Env variants from the same donor	314:349	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	11	theme	ripple	541:546	arg1	effect					548:553	a ripple effect	539:553	a ripple effect	539:553	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	5	12	dep	visualized	990:999	arg1	and					1031:1033	and	1031:1033	and	1031:1033	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	3	13	theme	variants	322:329	arg1	analysis					302:309	analysis	302:309	analysis of two Env variants from the same donor	302:349	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	4	14	theme	CD4	751:753	arg1	receptor					755:762	the CD4 receptor	747:762	the CD4 receptor	747:762	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	1	15	theme	immune	166:171	arg1	evasion					173:179	immune evasion	166:179	immune evasion	166:179	HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion.
33205023	3	16	theme	Env-wide	558:565	arg1	processing					574:583	Env-wide glycan processing	558:583	Env-wide glycan processing	558:583	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	4	17	theme	N262	671:674	arg1	glycan					676:681	the N262 glycan	667:681	the N262 glycan	667:681	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	0	18	theme	Glycan	0:5	arg1	Positioning					7:17	Glycan Positioning	0:17	Glycan Positioning	0:17	Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies.
33205023	3	19	theme	glycan	567:572	arg1	processing					574:583	Env-wide glycan processing	558:583	Env-wide glycan processing	558:583	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	0	20	theme	HIV-1	27:31	arg1	Density					51:57	HIV-1 Env Glycan-Shield Density	27:57	HIV-1 Env Glycan-Shield Density	27:57	Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies.
33205023	3	21	theme	virus	586:590	arg1	infectivity					592:602	virus infectivity	586:602	virus infectivity	586:602	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	22	theme	key	457:459	arg1	sites					477:481	key N-glycosylation sites	457:481	key N-glycosylation sites	457:481	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	6	23	theme	molecular	1184:1192	arg1	dynamics					1194:1201	molecular dynamics	1184:1201	molecular dynamics	1184:1201	This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
33205023	1	24	theme	HIV-1	101:105	arg1	Env					117:119	Env	117:119	Env	117:119	HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion.
33205023	1	24	theme	HIV-1	101:105	arg1	envelope					107:114	HIV-1 envelope	101:114	HIV-1 envelope (Env)	101:120	HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion.
33205023	3	25	theme	N-glycosylation	461:475	arg1	sites					477:481	key N-glycosylation sites	457:481	key N-glycosylation sites	457:481	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	0	26	theme	Glycan-Shield	37:49	arg1	Density					51:57	HIV-1 Env Glycan-Shield Density	27:57	HIV-1 Env Glycan-Shield Density	27:57	Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies.
33205023	6	27	theme	individual	1155:1164	arg1	glycans					1166:1172	individual glycans	1155:1172	individual glycans	1155:1172	This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
33205023	4	28	theme	limited	933:939	arg1	processing					948:957	limited glycan processing	933:957	limited glycan processing	933:957	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	5	29	theme	glycan	1103:1108	arg1	loss					1110:1113	a glycan loss	1101:1113	a glycan loss	1101:1113	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	2	30	theme	Env-protein-sugar	221:237	arg1	complex					239:245	the Env-protein-sugar complex	217:245	the Env-protein-sugar complex	217:245	How each glycan interacts to shape the Env-protein-sugar complex and affects Env function is not well understood.
33205023	0	31	theme	Env	33:35	arg1	Density					51:57	HIV-1 Env Glycan-Shield Density	27:57	HIV-1 Env Glycan-Shield Density	27:57	Glycan Positioning Impacts HIV-1 Env Glycan-Shield Density, Function, and Recognition by Antibodies.
33205023	3	32	contain	had	535:537	arg2	effect					548:553	a ripple effect	539:553	a ripple effect	539:553	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	32	contain	had	535:537	arg1	changes					446:452	changes	446:452	changes to key N-glycosylation sites	446:481	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	33	theme	N-glycosylation-site	398:417	arg1	composition					419:429	N-glycosylation-site composition	398:429	N-glycosylation-site composition	398:429	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	5	34	theme	oligosaccharide	1048:1062	arg1	positions					1064:1072	specific oligosaccharide positions	1039:1072	specific oligosaccharide positions	1039:1072	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	3	35	theme	functional	367:376	arg1	characteristics					378:392	functional characteristics	367:392	functional characteristics	367:392	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	36	theme	virus	631:635	arg1	neutralization					637:650	virus neutralization	631:650	virus neutralization	631:650	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	37	gly	N-glycosylation	461:475	arg2	sites					477:481	key N-glycosylation sites	457:481	key N-glycosylation sites	457:481	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	6	38	from	changes	1144:1150	arg1	glycans					1166:1172	individual glycans	1155:1172	individual glycans	1155:1172	This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
33205023	3	39	from	analysis	302:309	arg1	donor					345:349	the same donor	336:349	the same donor	336:349	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	4	40	theme	glycan-dependent	801:816	arg1	antibodies					831:840	several glycan-dependent neutralizing antibodies	793:840	several glycan-dependent neutralizing antibodies	793:840	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	3	41	theme	Env	496:498	arg1	structure					500:508	the Env structure	492:508	the Env structure	492:508	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	4	42	theme	Env	774:776	arg1	recognition					778:788	Env recognition	774:788	Env recognition by several glycan-dependent neutralizing antibodies	774:840	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	5	43	theme	glycan	1016:1021	arg1	density					1023:1029	glycan density	1016:1029	glycan density	1016:1029	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	2	44	theme	Env	259:261	arg1	function					263:270	Env function	259:270	Env function	259:270	How each glycan interacts to shape the Env-protein-sugar complex and affects Env function is not well understood.
33205023	4	45	dep	modulated	722:730	arg1	not					693:695	not	693:695	not	693:695	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	4	46	theme	CD4-binding	704:714	arg1	site					716:719	the CD4-binding site	700:719	the CD4-binding site	700:719	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
33205023	6	47	dep	Env-glycan	1236:1245	arg1	shield					1247:1252	shield	1247:1252	shield	1247:1252	This study demonstrates how changes in individual glycans can alter molecular dynamics, processing, and function of the Env-glycan shield.
33205023	5	48	dep	and	1031:1033	arg1	move					1078:1081	move	1078:1081	can move to compensate for a glycan loss	1074:1113	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	3	49	theme	distant	513:519	arg1	locations					521:529	distant locations	513:529	distant locations	513:529	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	50	theme	Env	318:320	arg1	variants					322:329	two Env variants	314:329	two Env variants from the same donor	314:349	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	3	51	theme	antibody	605:612	arg1	recognition					614:624	antibody recognition	605:624	antibody recognition	605:624	Here, analysis of two Env variants from the same donor, with differing functional characteristics and N-glycosylation-site composition, revealed that changes to key N-glycosylation sites affected the Env structure at distant locations and had a ripple effect on Env-wide glycan processing, virus infectivity, antibody recognition, and virus neutralization.
33205023	1	52	theme	impact	138:143	arg1	entry					156:160	impact virus-cell entry	138:160	impact virus-cell entry	138:160	HIV-1 envelope (Env) N-glycosylation impact virus-cell entry and immune evasion.
33205023	5	53	from	differences	1001:1011	arg1	density					1023:1029	glycan density	1016:1029	glycan density	1016:1029	Molecular-dynamic simulations visualized differences in glycan density and how specific oligosaccharide positions can move to compensate for a glycan loss.
33205023	4	54	theme	glycan	941:946	arg1	processing					948:957	limited glycan processing	933:957	limited glycan processing	933:957	Specifically, the N262 glycan, although not in the CD4-binding site, modulated Env binding to the CD4 receptor, affected Env recognition by several glycan-dependent neutralizing antibodies, and altered site-specific glycosylation heterogeneity, with, for example, N448 displaying limited glycan processing.
34885895	0	0	theme	Site	84:87	arg1	Prediction					89:98	Human N-Linked Glycosylation Site Prediction	55:98	Human N-Linked Glycosylation Site Prediction	55:98	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	2	1	gly	glycosylation	330:342	arg2	sites					344:348	glycosylation sites	330:348	glycosylation sites	330:348	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	6	2	theme	negative	897:904	arg1	approach					858:865	a deep learning-based approach	836:865	a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	836:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	2	theme	negative	897:904	arg1	sequences					906:914	the positive and negative sequences	880:914	the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	880:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	3	theme	predicted	1030:1038	arg1	features					1051:1058	predicted structural features	1030:1058	predicted structural features	1030:1058	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	0	4	theme	Glycosylation	70:82	arg1	Prediction					89:98	Human N-Linked Glycosylation Site Prediction	55:98	Human N-Linked Glycosylation Site Prediction	55:98	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	5	5	from	problem	798:804	arg1	regard					687:692	that regard	682:692	that regard	682:692	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	7	6	theme	%	1142:1142	arg1	SN					1113:1114	SN	1113:1114	SN	1113:1114	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	6	theme	%	1142:1142	arg1	MCC					1121:1123	MCC	1121:1123	MCC	1121:1123	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	6	theme	%	1142:1142	arg1	ACC					1130:1132	ACC	1130:1132	ACC	1130:1132	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	6	theme	%	1142:1142	arg1	SP					1117:1118	SP	1117:1118	SP	1117:1118	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	5	7	link	N-linked	723:730	arg1	sites					746:750	N-linked glycosylation sites	723:750	N-linked glycosylation sites confined to N-X-[S/T] sequons	723:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	8	8	theme	glycosylation	1363:1375	arg1	sites					1377:1381	N-Linked glycosylation sites	1354:1381	N-Linked glycosylation sites confined to N-X-[S/T] sequon	1354:1410	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	4	9	theme	N-X-[S/T	589:596	arg1	sequon					599:604	the N-X-[S/T] sequon	585:604	the N-X-[S/T] sequon	585:604	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	4	9	theme	N-X-[S/T	589:596	arg1	determinant					640:650	a necessary but not sufficient determinant	609:650	a necessary but not sufficient determinant for protein glycosylation	609:676	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	6	10	from	sequences	906:914	arg1	dataset					938:944	the human proteome dataset	919:944	the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	919:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	11	theme	human	923:927	arg1	dataset					938:944	the human proteome dataset	919:944	the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	919:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	8	12	theme	computational	1319:1331	arg1	technique					1333:1341	a robust computational technique	1310:1341	a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon	1310:1410	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	8	12	theme	computational	1319:1331	arg1	DeepNGlyPred					1294:1305	DeepNGlyPred	1294:1305	DeepNGlyPred	1294:1305	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	6	13	theme	positive	884:891	arg1	approach					858:865	a deep learning-based approach	836:865	a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	836:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	13	theme	positive	884:891	arg1	sequences					906:914	the positive and negative sequences	880:914	the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	880:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	7	14	theme	N-GlyDE	1187:1193	arg1	set					1212:1214	N-GlyDE independent test set	1187:1214	N-GlyDE independent test set	1187:1214	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	2	15	theme	glycosylation	330:342	arg1	sites					344:348	glycosylation sites	330:348	glycosylation sites	330:348	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	5	16	gly	glycosylation	732:744	arg2	sites					746:750	N-linked glycosylation sites	723:750	N-linked glycosylation sites confined to N-X-[S/T] sequons	723:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	3	17	gly	glycosylation	443:455	arg2	site					457:460	the glycosylation site	439:460	the glycosylation site	439:460	Most of the existing predictors for N-linked glycosylation utilize the information that the glycosylation site occurs at the N-X-[S/T] sequon, where X is any amino acid except proline.
34885895	3	18	link	N-linked	387:394	arg1	glycosylation					396:408	N-linked glycosylation	387:408	N-linked glycosylation	387:408	Most of the existing predictors for N-linked glycosylation utilize the information that the glycosylation site occurs at the N-X-[S/T] sequon, where X is any amino acid except proline.
34885895	3	19	theme	amino	509:513	arg1	acid					515:518	any amino acid	505:518	any amino acid	505:518	Most of the existing predictors for N-linked glycosylation utilize the information that the glycosylation site occurs at the N-X-[S/T] sequon, where X is any amino acid except proline.
34885895	5	20	theme	N-X-[S/T	764:771	arg1	sequons					774:780	N-X-[S/T] sequons	764:780	N-X-[S/T] sequons	764:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	1	21	theme	important	183:191	arg1	role					193:196	an important role	180:196	an important role	180:196	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	3	22	theme	N-linked	387:394	arg1	glycosylation					396:408	N-linked glycosylation	387:408	N-linked glycosylation	387:408	Most of the existing predictors for N-linked glycosylation utilize the information that the glycosylation site occurs at the N-X-[S/T] sequon, where X is any amino acid except proline.
34885895	7	23	theme	%	1150:1150	arg1	SN					1113:1114	SN	1113:1114	SN	1113:1114	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	23	theme	%	1150:1150	arg1	MCC					1121:1123	MCC	1121:1123	MCC	1121:1123	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	23	theme	%	1150:1150	arg1	ACC					1130:1132	ACC	1130:1132	ACC	1130:1132	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	23	theme	%	1150:1150	arg1	SP					1117:1118	SP	1117:1118	SP	1117:1118	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	24	from	SP	1117:1118	arg1	set					1212:1214	N-GlyDE independent test set	1187:1214	N-GlyDE independent test set	1187:1214	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	25	theme	%	1168:1168	arg1	SN					1113:1114	SN	1113:1114	SN	1113:1114	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	25	theme	%	1168:1168	arg1	MCC					1121:1123	MCC	1121:1123	MCC	1121:1123	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	25	theme	%	1168:1168	arg1	ACC					1130:1132	ACC	1130:1132	ACC	1130:1132	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	25	theme	%	1168:1168	arg1	SP					1117:1118	SP	1117:1118	SP	1117:1118	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	5	26	theme	important	788:796	arg1	problem					798:804	an important problem	785:804	an important problem	785:804	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	5	26	theme	important	788:796	arg1	prediction					709:718	computational prediction	695:718	computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons	695:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	7	27	theme	independent	1195:1205	arg1	set					1212:1214	N-GlyDE independent test set	1187:1214	N-GlyDE independent test set	1187:1214	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	3	28	theme	existing	363:370	arg1	predictors					372:381	the existing predictors	359:381	the existing predictors for N-linked glycosylation	359:408	Most of the existing predictors for N-linked glycosylation utilize the information that the glycosylation site occurs at the N-X-[S/T] sequon, where X is any amino acid except proline.
34885895	8	29	theme	N-Linked	1354:1361	arg1	sites					1377:1381	N-Linked glycosylation sites	1354:1381	N-Linked glycosylation sites confined to N-X-[S/T] sequon	1354:1410	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	9	30	theme	glycobiology	1460:1471	arg1	community					1473:1481	the glycobiology community	1456:1481	the glycobiology community	1456:1481	DeepNGlyPred will be a useful resource for the glycobiology community.
34885895	9	31	theme	useful	1436:1441	arg1	resource					1443:1450	a useful resource	1434:1450	a useful resource for the glycobiology community	1434:1481	DeepNGlyPred will be a useful resource for the glycobiology community.
34885895	9	31	theme	useful	1436:1441	arg1	DeepNGlyPred					1413:1424	DeepNGlyPred	1413:1424	DeepNGlyPred	1413:1424	DeepNGlyPred will be a useful resource for the glycobiology community.
34885895	6	32	theme	proteome	929:936	arg1	dataset					938:944	the human proteome dataset	919:944	the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	919:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	33	dep	report	816:821	arg1	DeepNGlyPred					823:834	DeepNGlyPred	823:834	DeepNGlyPred	823:834	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	3	34	theme	N-X-[S/T	476:483	arg1	sequon					486:491	the N-X-[S/T] sequon	472:491	the N-X-[S/T] sequon	472:491	Most of the existing predictors for N-linked glycosylation utilize the information that the glycosylation site occurs at the N-X-[S/T] sequon, where X is any amino acid except proline.
34885895	0	35	theme	Deep	16:19	arg1	Approach					42:49	A Deep Neural Network-Based Approach	14:49	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.	0:99	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	7	36	from	MCC	1121:1123	arg1	set					1212:1214	N-GlyDE independent test set	1187:1214	N-GlyDE independent test set	1187:1214	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	2	37	theme	sites	344:348	arg1	characterization					310:325	the characterization	306:325	the characterization of glycosylation sites	306:348	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	6	38	theme	sequence-based	986:999	arg1	gapped-dipeptide					1011:1026	gapped-dipeptide	1011:1026	gapped-dipeptide	1011:1026	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	38	theme	sequence-based	986:999	arg1	features					1001:1008	sequence-based features	986:1008	sequence-based features (gapped-dipeptide)	986:1027	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	5	39	theme	N-linked	723:730	arg1	sites					746:750	N-linked glycosylation sites	723:750	N-linked glycosylation sites confined to N-X-[S/T] sequons	723:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	1	40	theme	N-linked	109:116	arg1	glycosylation					118:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	1	40	theme	N-linked	109:116	arg1	modification					156:167	a post-translational modification	135:167	a post-translational modification that plays an important role in a myriad of biological processes	135:232	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	4	41	theme	sufficient	629:638	arg1	sequon					599:604	the N-X-[S/T] sequon	585:604	the N-X-[S/T] sequon	585:604	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	4	41	theme	sufficient	629:638	arg1	determinant					640:650	a necessary but not sufficient determinant	609:650	a necessary but not sufficient determinant for protein glycosylation	609:676	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	0	42	theme	Network-Based	28:40	arg1	Approach					42:49	A Deep Neural Network-Based Approach	14:49	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.	0:99	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	5	43	theme	glycosylation	732:744	arg1	sites					746:750	N-linked glycosylation sites	723:750	N-linked glycosylation sites confined to N-X-[S/T] sequons	723:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	4	44	theme	protein	656:662	arg1	glycosylation					664:676	protein glycosylation	656:676	protein glycosylation	656:676	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	1	45	theme	biological	213:222	arg1	processes					224:232	biological processes	213:232	biological processes	213:232	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	0	46	theme	Neural	21:26	arg1	Approach					42:49	A Deep Neural Network-Based Approach	14:49	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.	0:99	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	7	47	from	ACC	1130:1132	arg1	set					1212:1214	N-GlyDE independent test set	1187:1214	N-GlyDE independent test set	1187:1214	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	5	48	theme	sites	746:750	arg1	problem					798:804	an important problem	785:804	an important problem	785:804	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	5	48	theme	sites	746:750	arg1	prediction					709:718	computational prediction	695:718	computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons	695:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	2	49	theme	prediction	249:258	arg1	approaches					260:269	Computational prediction approaches	235:269	Computational prediction approaches	235:269	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	2	49	theme	prediction	249:258	arg1	methods					294:300	complementary methods	280:300	complementary methods for the characterization of glycosylation sites	280:348	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	4	50	gly	glycosylated	566:577	arg1	sequons					554:560	Not all N-X-[S/T] sequons	536:560	Not all N-X-[S/T] sequons	536:560	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	1	51	theme	processes	224:232	arg1	myriad					203:208	a myriad	201:208	a myriad of biological processes	201:232	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	3	52	theme	glycosylation	443:455	arg1	site					457:460	the glycosylation site	439:460	the glycosylation site	439:460	Most of the existing predictors for N-linked glycosylation utilize the information that the glycosylation site occurs at the N-X-[S/T] sequon, where X is any amino acid except proline.
34885895	4	53	theme	N-X-[S/T	544:551	arg1	sequons					554:560	Not all N-X-[S/T] sequons	536:560	Not all N-X-[S/T] sequons	536:560	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	6	54	theme	evolutionary	1065:1076	arg1	information					1078:1088	evolutionary information	1065:1088	evolutionary information	1065:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	0	55	theme	Human	55:59	arg1	Prediction					89:98	Human N-Linked Glycosylation Site Prediction	55:98	Human N-Linked Glycosylation Site Prediction	55:98	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	2	56	theme	Computational	235:247	arg1	approaches					260:269	Computational prediction approaches	235:269	Computational prediction approaches	235:269	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	2	56	theme	Computational	235:247	arg1	methods					294:300	complementary methods	280:300	complementary methods for the characterization of glycosylation sites	280:348	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	7	57	theme	compared	1242:1249	arg1	approaches					1251:1260	the compared approaches	1238:1260	the compared approaches	1238:1260	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	8	58	gly	glycosylation	1363:1375	arg2	sites					1377:1381	N-Linked glycosylation sites	1354:1381	N-Linked glycosylation sites confined to N-X-[S/T] sequon	1354:1410	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	7	59	theme	test	1207:1210	arg1	set					1212:1214	N-GlyDE independent test set	1187:1214	N-GlyDE independent test set	1187:1214	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	8	60	theme	N-X-[S/T	1395:1402	arg1	sequon					1405:1410	N-X-[S/T] sequon	1395:1410	N-X-[S/T] sequon	1395:1410	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	7	61	theme	0.60	1153:1156	arg1	SN					1113:1114	SN	1113:1114	SN	1113:1114	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	61	theme	0.60	1153:1156	arg1	MCC					1121:1123	MCC	1121:1123	MCC	1121:1123	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	61	theme	0.60	1153:1156	arg1	ACC					1130:1132	ACC	1130:1132	ACC	1130:1132	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	7	61	theme	0.60	1153:1156	arg1	SP					1117:1118	SP	1117:1118	SP	1117:1118	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	5	62	theme	computational	695:707	arg1	problem					798:804	an important problem	785:804	an important problem	785:804	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	5	62	theme	computational	695:707	arg1	prediction					709:718	computational prediction	695:718	computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons	695:780	In that regard, computational prediction of N-linked glycosylation sites confined to N-X-[S/T] sequons is an important problem.
34885895	1	63	theme	Protein	101:107	arg1	glycosylation					118:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	1	63	theme	Protein	101:107	arg1	modification					156:167	a post-translational modification	135:167	a post-translational modification that plays an important role in a myriad of biological processes	135:232	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	4	64	theme	necessary	611:619	arg1	sequon					599:604	the N-X-[S/T] sequon	585:604	the N-X-[S/T] sequon	585:604	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	4	64	theme	necessary	611:619	arg1	determinant					640:650	a necessary but not sufficient determinant	609:650	a necessary but not sufficient determinant for protein glycosylation	609:676	Not all N-X-[S/T] sequons are glycosylated, thus the N-X-[S/T] sequon is a necessary but not sufficient determinant for protein glycosylation.
34885895	6	65	theme	learning-based	843:856	arg1	approach					858:865	a deep learning-based approach	836:865	a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	836:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	65	theme	learning-based	843:856	arg1	sequences					906:914	the positive and negative sequences	880:914	the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	880:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	2	66	theme	complementary	280:292	arg1	approaches					260:269	Computational prediction approaches	235:269	Computational prediction approaches	235:269	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	2	66	theme	complementary	280:292	arg1	methods					294:300	complementary methods	280:300	complementary methods for the characterization of glycosylation sites	280:348	Computational prediction approaches serve as complementary methods for the characterization of glycosylation sites.
34885895	1	67	theme	post-translational	137:154	arg1	glycosylation					118:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	1	67	theme	post-translational	137:154	arg1	modification					156:167	a post-translational modification	135:167	a post-translational modification that plays an important role in a myriad of biological processes	135:232	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	8	68	theme	robust	1312:1317	arg1	technique					1333:1341	a robust computational technique	1310:1341	a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon	1310:1410	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	8	68	theme	robust	1312:1317	arg1	DeepNGlyPred					1294:1305	DeepNGlyPred	1294:1305	DeepNGlyPred	1294:1305	These results demonstrate that DeepNGlyPred is a robust computational technique to predict N-Linked glycosylation sites confined to N-X-[S/T] sequon.
34885895	0	69	theme	N-Linked	61:68	arg1	Prediction					89:98	Human N-Linked Glycosylation Site Prediction	55:98	Human N-Linked Glycosylation Site Prediction	55:98	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	6	70	theme	deep	838:841	arg1	approach					858:865	a deep learning-based approach	836:865	a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	836:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	6	70	theme	deep	838:841	arg1	sequences					906:914	the positive and negative sequences	880:914	the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information	880:1088	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34885895	7	71	from	SN	1113:1114	arg1	set					1212:1214	N-GlyDE independent test set	1187:1214	N-GlyDE independent test set	1187:1214	DeepNGlyPred produces SN, SP, MCC, and ACC of 88.62%, 73.92%, 0.60, and 79.41%, respectively on N-GlyDE independent test set, which is better than the compared approaches.
34885895	1	72	link	N-linked	109:116	arg1	glycosylation					118:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation	101:130	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	1	72	link	N-linked	109:116	arg1	modification					156:167	a post-translational modification	135:167	a post-translational modification that plays an important role in a myriad of biological processes	135:232	Protein N-linked glycosylation is a post-translational modification that plays an important role in a myriad of biological processes.
34885895	0	73	dep	DeepNGlyPred	0:11	arg1	Approach					42:49	A Deep Neural Network-Based Approach	14:49	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.	0:99	DeepNGlyPred: A Deep Neural Network-Based Approach for Human N-Linked Glycosylation Site Prediction.
34885895	6	74	theme	structural	1040:1049	arg1	features					1051:1058	predicted structural features	1030:1058	predicted structural features	1030:1058	Here, we report DeepNGlyPred a deep learning-based approach that encodes the positive and negative sequences in the human proteome dataset (extracted from N-GlycositeAtlas) using sequence-based features (gapped-dipeptide), predicted structural features, and evolutionary information.
34796531	4	0	theme	pest	969:972	arg1	egg					866:868	egg	866:868	egg	866:868	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	0	theme	pest	969:972	arg1	worldwide					974:982	pest worldwide	969:982	pest worldwide	969:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	6	1	theme	pentasaccharide	1211:1225	arg1	O-glycan					1227:1234	pentasaccharide O-glycan	1211:1234	pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA)	1211:1264	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	6	1	theme	pentasaccharide	1211:1225	arg1	GalNAcGlcA					1254:1263	O-GalNAc(GalGlcA)GalNAcGlcA	1237:1263	O-GalNAc(GalGlcA)GalNAcGlcA	1237:1263	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	4	2	theme	resonance	731:739	arg1	MS					768:769	MS	768:769	MS	768:769	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	2	theme	resonance	731:739	arg1	spectrometry					754:765	ion cyclotron resonance (FTICR) mass spectrometry	717:765	ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	717:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	2	3	theme	modification	395:406	arg1	knowledge					377:385	our knowledge	373:385	our knowledge of this modification in insects	373:417	Despite the importance of protein glycosylation in numerous biological processes, our knowledge of this modification in insects is far from complete.
34796531	1	4	theme	proteins	281:288	arg1	activities					261:270	activities	261:270	activities	261:270	Eukaryotic cells can decorate their proteins with carbohydrate structures or glycans, significantly affecting the properties and activities of these proteins.
34796531	1	4	theme	proteins	281:288	arg1	properties					246:255	properties	246:255	properties	246:255	Eukaryotic cells can decorate their proteins with carbohydrate structures or glycans, significantly affecting the properties and activities of these proteins.
34796531	6	5	from	stage	1328:1332	arg1	insects					1383:1389	holometabolous insects	1368:1389	holometabolous insects	1368:1389	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	4	6	theme	larva	871:875	arg1	stages					856:861	the different developmental stages	828:861	the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide	828:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	1	7	theme	carbohydrate	182:193	arg1	structures					195:204	carbohydrate structures	182:204	carbohydrate structures	182:204	Eukaryotic cells can decorate their proteins with carbohydrate structures or glycans, significantly affecting the properties and activities of these proteins.
34796531	6	8	theme	intermediate	1315:1326	arg1	stage					1328:1332	the intermediate stage	1311:1332	the intermediate stage between larval	1311:1347	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	7	9	gly	glycosylation	1604:1616	arg1	insects					1640:1646	insects	1640:1646	insects	1640:1646	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	6	10	theme	GalGlcA	1246:1252	arg1	O-glycan					1227:1234	pentasaccharide O-glycan	1211:1234	pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA)	1211:1264	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	6	10	theme	GalGlcA	1246:1252	arg1	GalNAcGlcA					1254:1263	O-GalNAc(GalGlcA)GalNAcGlcA	1237:1263	O-GalNAc(GalGlcA)GalNAcGlcA	1237:1263	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	5	11	theme	O-glycan	1004:1011	arg1	profile					1013:1019	the O-glycan profile	1000:1019	the O-glycan profile	1000:1019	The results on the O-glycan profile showed that the mucin-type glycans dominate the O-glycome of the red flour beetle.
34796531	2	12	theme	glycosylation	325:337	arg1	importance					303:312	the importance	299:312	the importance of protein glycosylation in numerous biological processes	299:370	Despite the importance of protein glycosylation in numerous biological processes, our knowledge of this modification in insects is far from complete.
34796531	6	13	theme	insect	1411:1416	arg1	metamorphosis					1418:1430	insect metamorphosis	1411:1430	insect metamorphosis	1411:1430	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	7	14	theme	N-glycan	1511:1518	arg1	profile					1520:1526	the N-glycan profile	1507:1526	the N-glycan profile	1507:1526	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	4	15	theme	pupa	878:881	arg1	stages					856:861	the different developmental stages	828:861	the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide	828:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	2	16	theme	protein	317:323	arg1	glycosylation					325:337	protein glycosylation	317:337	protein glycosylation	317:337	Despite the importance of protein glycosylation in numerous biological processes, our knowledge of this modification in insects is far from complete.
34796531	7	17	theme	insects	1640:1646	arg1	development					1625:1635	the development	1621:1635	the development of insects	1621:1646	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	4	18	theme	cyclotron	721:729	arg1	MS					768:769	MS	768:769	MS	768:769	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	18	theme	cyclotron	721:729	arg1	spectrometry					754:765	ion cyclotron resonance (FTICR) mass spectrometry	717:765	ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	717:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	19	theme	FTICR	742:746	arg1	MS					768:769	MS	768:769	MS	768:769	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	19	theme	FTICR	742:746	arg1	spectrometry					754:765	ion cyclotron resonance (FTICR) mass spectrometry	717:765	ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	717:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	6	20	theme	O-GalNAc	1237:1244	arg1	O-glycan					1227:1234	pentasaccharide O-glycan	1211:1234	pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA)	1211:1264	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	6	20	theme	O-GalNAc	1237:1244	arg1	GalNAcGlcA					1254:1263	O-GalNAc(GalGlcA)GalNAcGlcA	1237:1263	O-GalNAc(GalGlcA)GalNAcGlcA	1237:1263	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	2	21	from	knowledge	377:385	arg1	insects					411:417	insects	411:417	insects	411:417	Despite the importance of protein glycosylation in numerous biological processes, our knowledge of this modification in insects is far from complete.
34796531	6	22	theme	mucin-type	1144:1153	arg1	O-glycans					1155:1163	the more complex mucin-type O-glycans	1127:1163	the more complex mucin-type O-glycans	1127:1163	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	5	23	from	results	989:995	arg1	profile					1013:1019	the O-glycan profile	1000:1019	the O-glycan profile	1000:1019	The results on the O-glycan profile showed that the mucin-type glycans dominate the O-glycome of the red flour beetle.
34796531	6	24	theme	adult	1353:1357	arg1	stage					1359:1363	adult stage	1353:1363	adult stage in holometabolous insects	1353:1389	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	5	25	theme	red	1086:1088	arg1	beetle					1096:1101	the red flour beetle	1082:1101	the red flour beetle	1082:1101	The results on the O-glycan profile showed that the mucin-type glycans dominate the O-glycome of the red flour beetle.
34796531	6	26	theme	holometabolous	1368:1381	arg1	insects					1383:1389	holometabolous insects	1368:1389	holometabolous insects	1368:1389	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	6	27	theme	complex	1136:1142	arg1	O-glycans					1155:1163	the more complex mucin-type O-glycans	1127:1163	the more complex mucin-type O-glycans	1127:1163	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	4	28	theme	important	942:950	arg1	egg					866:868	egg	866:868	egg	866:868	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	28	theme	important	942:950	arg1	model					959:963	an important insect model	939:963	an important insect model	939:963	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	0	29	theme	O-glycan	14:21	arg1	analysis					31:38	Developmental O-glycan profile analysis	0:38	Developmental O-glycan profile analysis	0:38	Developmental O-glycan profile analysis shows pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum.
34796531	5	30	theme	flour	1090:1094	arg1	beetle					1096:1101	the red flour beetle	1082:1101	the red flour beetle	1082:1101	The results on the O-glycan profile showed that the mucin-type glycans dominate the O-glycome of the red flour beetle.
34796531	3	31	theme	developmental	588:600	arg1	stage					602:606	a specific developmental stage	577:606	a specific developmental stage	577:606	While N-glycosylation is the most studied, the study of O-glycans in insects is still very fragmentary and these studies are limited to a specific developmental stage or a specific tissue.
34796531	6	32	from	stage	1304:1308	arg1	insects					1383:1389	holometabolous insects	1368:1389	holometabolous insects	1368:1389	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	0	33	theme	Developmental	0:12	arg1	analysis					31:38	Developmental O-glycan profile analysis	0:38	Developmental O-glycan profile analysis	0:38	Developmental O-glycan profile analysis shows pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum.
34796531	4	34	theme	egg	866:868	arg1	stages					856:861	the different developmental stages	828:861	the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide	828:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	2	35	theme	biological	351:360	arg1	processes					362:370	numerous biological processes	342:370	numerous biological processes	342:370	Despite the importance of protein glycosylation in numerous biological processes, our knowledge of this modification in insects is far from complete.
34796531	4	36	theme	spectrometry	754:765	arg1	technology					772:781	ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	717:781	ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	717:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	37	theme	flour	905:909	arg1	beetle					911:916	the red flour beetle	897:916	the red flour beetle	897:916	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	6	38	from	change	1454:1459	arg1	profile					1484:1490	the insect O-glycan profile	1464:1490	the insect O-glycan profile	1464:1490	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	2	39	theme	numerous	342:349	arg1	processes					362:370	numerous biological processes	342:370	numerous biological processes	342:370	Despite the importance of protein glycosylation in numerous biological processes, our knowledge of this modification in insects is far from complete.
34796531	0	40	dep	O-glycans	73:81	arg1	linked					87:92	linked	87:92	are linked with pupation of Tribolium castaneum	83:129	Developmental O-glycan profile analysis shows pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum.
34796531	4	41	theme	matrix-assisted	647:661	arg1	MALDI					692:696	MALDI	692:696	MALDI	692:696	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	41	theme	matrix-assisted	647:661	arg1	desorption/ionization					669:689	matrix-assisted laser desorption/ionization	647:689	matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	647:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	0	42	theme	profile	23:29	arg1	analysis					31:38	Developmental O-glycan profile analysis	0:38	Developmental O-glycan profile analysis	0:38	Developmental O-glycan profile analysis shows pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum.
34796531	4	43	theme	red	901:903	arg1	beetle					911:916	the red flour beetle	897:916	the red flour beetle	897:916	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	3	44	theme	specific	579:586	arg1	stage					602:606	a specific developmental stage	577:606	a specific developmental stage	577:606	While N-glycosylation is the most studied, the study of O-glycans in insects is still very fragmentary and these studies are limited to a specific developmental stage or a specific tissue.
34796531	6	45	theme	insect	1468:1473	arg1	profile					1484:1490	the insect O-glycan profile	1464:1490	the insect O-glycan profile	1464:1490	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	3	46	theme	O-glycans	497:505	arg1	study					488:492	the study	484:492	the study of O-glycans in insects	484:516	While N-glycosylation is the most studied, the study of O-glycans in insects is still very fragmentary and these studies are limited to a specific developmental stage or a specific tissue.
34796531	3	46	theme	O-glycans	497:505	arg1	fragmentary					532:542	fragmentary	532:542	fragmentary	532:542	While N-glycosylation is the most studied, the study of O-glycans in insects is still very fragmentary and these studies are limited to a specific developmental stage or a specific tissue.
34796531	0	47	theme	pentasaccharide	46:60	arg1	O-glycans					73:81	pentasaccharide mucin-type O-glycans	46:81	pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum	46:129	Developmental O-glycan profile analysis shows pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum.
34796531	3	48	theme	specific	613:620	arg1	tissue					622:627	a specific tissue	611:627	a specific tissue	611:627	While N-glycosylation is the most studied, the study of O-glycans in insects is still very fragmentary and these studies are limited to a specific developmental stage or a specific tissue.
34796531	4	49	theme	desorption/ionization	669:689	arg1	-Fourier					698:705	matrix-assisted laser desorption/ionization (MALDI)-Fourier	647:705	matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	647:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	50	theme	beetle	911:916	arg1	egg					866:868	egg	866:868	egg	866:868	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	50	theme	beetle	911:916	arg1	model					959:963	an important insect model	939:963	an important insect model	939:963	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	50	theme	beetle	911:916	arg1	adult					888:892	adult	888:892	adult	888:892	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	50	theme	beetle	911:916	arg1	larva					871:875	larva	871:875	larva	871:875	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	50	theme	beetle	911:916	arg1	worldwide					974:982	pest worldwide	969:982	pest worldwide	969:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	50	theme	beetle	911:916	arg1	pupa					878:881	pupa	878:881	pupa	878:881	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	3	51	dep	most	470:473	arg1	is					463:464	is	463:464	is the most studied	463:481	While N-glycosylation is the most studied, the study of O-glycans in insects is still very fragmentary and these studies are limited to a specific developmental stage or a specific tissue.
34796531	4	52	theme	laser	663:667	arg1	MALDI					692:696	MALDI	692:696	MALDI	692:696	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	52	theme	laser	663:667	arg1	desorption/ionization					669:689	matrix-assisted laser desorption/ionization	647:689	matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	647:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	7	53	theme	glycosylation	1604:1616	arg1	role					1588:1591	the role	1584:1591	the role of protein glycosylation in the development of insects	1584:1646	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	4	54	theme	adult	888:892	arg1	stages					856:861	the different developmental stages	828:861	the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide	828:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	7	55	theme	protein	1596:1602	arg1	glycosylation					1604:1616	protein glycosylation	1596:1616	protein glycosylation	1596:1616	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	4	56	theme	developmental	842:854	arg1	stages					856:861	the different developmental stages	828:861	the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide	828:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	3	57	from	study	488:492	arg1	insects					510:516	insects	510:516	insects	510:516	While N-glycosylation is the most studied, the study of O-glycans in insects is still very fragmentary and these studies are limited to a specific developmental stage or a specific tissue.
34796531	1	58	theme	Eukaryotic	132:141	arg1	cells					143:147	Eukaryotic cells	132:147	Eukaryotic cells	132:147	Eukaryotic cells can decorate their proteins with carbohydrate structures or glycans, significantly affecting the properties and activities of these proteins.
34796531	0	59	theme	mucin-type	62:71	arg1	O-glycans					73:81	pentasaccharide mucin-type O-glycans	46:81	pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum	46:129	Developmental O-glycan profile analysis shows pentasaccharide mucin-type O-glycans are linked with pupation of Tribolium castaneum.
34796531	6	60	theme	pupa	1299:1302	arg1	stage					1304:1308	the pupa stage	1295:1308	the pupa stage	1295:1308	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	6	61	from	stage	1359:1363	arg1	insects					1383:1389	holometabolous insects	1368:1389	holometabolous insects	1368:1389	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	4	62	theme	different	832:840	arg1	stages					856:861	the different developmental stages	828:861	the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide	828:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	63	used	used	787:790	arg2	-Fourier					698:705	matrix-assisted laser desorption/ionization (MALDI)-Fourier	647:705	matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	647:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	64	dep	-Fourier	698:705	arg1	transform					707:715	transform	707:715	transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	707:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	65	theme	mass	749:752	arg1	MS					768:769	MS	768:769	MS	768:769	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	65	theme	mass	749:752	arg1	spectrometry					754:765	ion cyclotron resonance (FTICR) mass spectrometry	717:765	ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	717:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	2	66	from	importance	303:312	arg1	processes					362:370	numerous biological processes	342:370	numerous biological processes	342:370	Despite the importance of protein glycosylation in numerous biological processes, our knowledge of this modification in insects is far from complete.
34796531	1	67	dep	properties	246:255	arg1	the					242:244	the	242:244	the	242:244	Eukaryotic cells can decorate their proteins with carbohydrate structures or glycans, significantly affecting the properties and activities of these proteins.
34796531	6	68	theme	O-glycan	1475:1482	arg1	profile					1484:1490	the insect O-glycan profile	1464:1490	the insect O-glycan profile	1464:1490	Interestingly, some of the more complex mucin-type O-glycans, such as a tetra- (O-GalNAcGalGlcAGalNAc) and pentasaccharide O-glycan (O-GalNAc(GalGlcA)GalNAcGlcA), were highly abundant during the pupa stage, the intermediate stage between larval and adult stage in holometabolous insects, demonstrating that insect metamorphosis is accompanied with a change in the insect O-glycan profile.
34796531	7	69	from	role	1588:1591	arg1	development					1625:1635	the development	1621:1635	the development of insects	1621:1646	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	5	70	theme	mucin-type	1037:1046	arg1	glycans					1048:1054	the mucin-type glycans	1033:1054	the mucin-type glycans	1033:1054	The results on the O-glycan profile showed that the mucin-type glycans dominate the O-glycome of the red flour beetle.
34796531	4	71	theme	ion	717:719	arg1	MS					768:769	MS	768:769	MS	768:769	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	71	theme	ion	717:719	arg1	spectrometry					754:765	ion cyclotron resonance (FTICR) mass spectrometry	717:765	ion cyclotron resonance (FTICR) mass spectrometry (MS) technology	717:781	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	7	72	theme	current	1533:1539	arg1	data					1541:1544	the current data	1529:1544	the current data	1529:1544	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	7	72	theme	current	1533:1539	arg1	foundation					1552:1561	a foundation	1550:1561	a foundation to better understand the role of protein glycosylation in the development of insects	1550:1646	Together with the N-glycan profile, the current data are a foundation to better understand the role of protein glycosylation in the development of insects.
34796531	4	73	theme	insect	952:957	arg1	egg					866:868	egg	866:868	egg	866:868	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	4	73	theme	insect	952:957	arg1	model					959:963	an important insect model	939:963	an important insect model	939:963	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34796531	5	74	theme	beetle	1096:1101	arg1	O-glycome					1069:1077	the O-glycome	1065:1077	the O-glycome of the red flour beetle	1065:1101	The results on the O-glycan profile showed that the mucin-type glycans dominate the O-glycome of the red flour beetle.
34796531	4	75	theme	O-glycan	807:814	arg1	profile					816:822	the O-glycan profile	803:822	the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide	803:982	In this article, matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) technology was used to analyze the O-glycan profile for the different developmental stages of egg, larva, pupa, and adult of the red flour beetle Tribolium castaneum, an important insect model and pest worldwide.
34670086	10	0	gly	glycosylation	1688:1700	arg1	systems					1628:1634	matched expression systems	1609:1634	matched expression systems	1609:1634	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	10	0	gly	glycosylation	1688:1700	arg1	protein					1715:1721	the spike protein	1705:1721	the spike protein	1705:1721	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	10	1	theme	protein	1651:1657	arg1	architecture					1659:1670	the quaternary protein architecture	1636:1670	the quaternary protein architecture	1636:1670	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	5	2	link	O-linked	686:693	arg1	glycosylation					695:707	O-linked glycosylation	686:707	O-linked glycosylation	686:707	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	1	3	theme	viral	238:242	arg1	target					244:249	this key viral target	229:249	this key viral target	229:249	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	0	4	theme	Structural	76:85	arg1	Restraints					87:96	Quaternary Structural Restraints	65:96	Quaternary Structural Restraints	65:96	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.
34670086	9	5	theme	putative	1479:1486	arg1	ions					1387:1390	fragmentation ions	1373:1390	fragmentation ions arising from trace levels of truncated N-linked glycans	1373:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	5	theme	putative	1479:1486	arg1	structures					1504:1513	proximal putative O-linked glycan structures	1470:1513	proximal putative O-linked glycan structures	1470:1513	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	4	6	gly	glycosylation	575:587	arg1	protein					653:659	the native-like soluble trimeric protein	620:659	the native-like soluble trimeric protein	620:659	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	1	7	theme	protein	157:163	arg1	glycosylation					117:129	the glycosylation	113:129	the glycosylation of the envelope spike (S) protein of SARS-CoV-2	113:177	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	6	8	theme	O-linked	1004:1011	arg1	glycan					1013:1018	a single unambiguous O-linked glycan	983:1018	a single unambiguous O-linked glycan	983:1018	In the native-like trimer, we observe a single unambiguous O-linked glycan at T323, which displays very low occupancy.
34670086	1	9	theme	target	244:249	arg1	surface					218:224	the antigenic surface	204:224	the antigenic surface of this key viral target	204:249	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	5	10	theme	N-linked	725:732	arg1	glycosylation					734:746	N-linked glycosylation	725:746	N-linked glycosylation using the enzymatic inhibitor, kifunensine	725:789	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	4	11	theme	binding	506:512	arg1	RBD					522:524	RBD	522:524	RBD	522:524	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	4	11	theme	binding	506:512	arg1	domain					514:519	the receptor binding domain	493:519	the receptor binding domain (RBD)	493:525	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	9	12	link	O-linked	1488:1495	arg1	ions					1387:1390	fragmentation ions	1373:1390	fragmentation ions arising from trace levels of truncated N-linked glycans	1373:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	12	link	O-linked	1488:1495	arg1	structures					1504:1513	proximal putative O-linked glycan structures	1470:1513	proximal putative O-linked glycan structures	1470:1513	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	2	13	theme	protein	276:282	arg1	architecture					284:295	the underlying protein architecture	261:295	the underlying protein architecture	261:295	However, the underlying protein architecture may significantly influence glycan occupancy and processing.
34670086	5	14	dep	Orbitrap	908:915	arg1	Eclipse					917:923	Eclipse	917:923	Eclipse Tribrid instrument	917:942	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	4	15	theme	O-linked	566:573	arg1	glycosylation					575:587	O-linked glycosylation	566:587	O-linked glycosylation	566:587	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	1	16	dep	spike	147:151	arg1	S					154:154	S	154:154	S	154:154	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	9	17	link	N-linked	1431:1438	arg1	glycans					1440:1446	truncated N-linked glycans	1421:1446	truncated N-linked glycans	1421:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	2	18	theme	underlying	265:274	arg1	architecture					284:295	the underlying protein architecture	261:295	the underlying protein architecture	261:295	However, the underlying protein architecture may significantly influence glycan occupancy and processing.
34670086	9	19	theme	O-linked	1488:1495	arg1	ions					1387:1390	fragmentation ions	1373:1390	fragmentation ions arising from trace levels of truncated N-linked glycans	1373:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	19	theme	O-linked	1488:1495	arg1	structures					1504:1513	proximal putative O-linked glycan structures	1470:1513	proximal putative O-linked glycan structures	1470:1513	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	1	20	theme	spike	147:151	arg1	protein					157:163	the envelope spike (S) protein	134:163	the envelope spike (S) protein of SARS-CoV-2	134:177	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	1	21	gly	glycosylation	117:129	arg1	protein					157:163	the envelope spike (S) protein	134:163	the envelope spike (S) protein of SARS-CoV-2	134:177	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	7	22	theme	glycosylation	1103:1115	arg1	glycosylation					1103:1115	O-linked glycosylation	1094:1115	O-linked glycosylation	1094:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	7	22	theme	glycosylation	1103:1115	arg1	sites					1085:1089	several sites	1077:1089	several sites of O-linked glycosylation	1077:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	9	23	theme	glycan	1497:1502	arg1	ions					1387:1390	fragmentation ions	1373:1390	fragmentation ions arising from trace levels of truncated N-linked glycans	1373:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	23	theme	glycan	1497:1502	arg1	structures					1504:1513	proximal putative O-linked glycan structures	1470:1513	proximal putative O-linked glycan structures	1470:1513	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	5	24	link	N-linked	725:732	arg1	glycosylation					734:746	N-linked glycosylation	725:746	N-linked glycosylation using the enzymatic inhibitor, kifunensine	725:789	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	9	25	theme	proximal	1470:1477	arg1	ions					1387:1390	fragmentation ions	1373:1390	fragmentation ions arising from trace levels of truncated N-linked glycans	1373:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	25	theme	proximal	1470:1477	arg1	structures					1504:1513	proximal putative O-linked glycan structures	1470:1513	proximal putative O-linked glycan structures	1470:1513	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	4	26	theme	soluble	636:642	arg1	protein					653:659	the native-like soluble trimeric protein	620:659	the native-like soluble trimeric protein	620:659	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	3	27	theme	recombinant	403:413	arg1	fragments					415:423	different recombinant fragments	393:423	different recombinant fragments of S protein	393:436	There is, therefore, potential for different recombinant fragments of S protein to display divergent glycosylation.
34670086	9	28	theme	analytical	1327:1336	arg1	approach					1338:1345	Our analytical approach	1323:1345	Our analytical approach	1323:1345	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	29	theme	N-linked	1431:1438	arg1	glycans					1440:1446	truncated N-linked glycans	1421:1446	truncated N-linked glycans	1421:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	1	30	theme	SARS-CoV-2	168:177	arg1	protein					157:163	the envelope spike (S) protein	134:163	the envelope spike (S) protein of SARS-CoV-2	134:177	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	9	31	theme	fragments	1559:1567	arg1	paucity					1537:1543	a paucity	1535:1543	a paucity of diagnostic fragments	1535:1567	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	7	32	used	occupied	1205:1212	arg2	T323					1176:1179	T323	1176:1179	T323	1176:1179	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	5	33	theme	enzymatic	758:766	arg1	inhibitor					768:776	the enzymatic inhibitor	754:776	the enzymatic inhibitor	754:776	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	5	33	theme	enzymatic	758:766	arg1	kifunensine					779:789	kifunensine	779:789	kifunensine	779:789	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	3	34	theme	S	428:428	arg1	protein					430:436	S protein	428:436	S protein	428:436	There is, therefore, potential for different recombinant fragments of S protein to display divergent glycosylation.
34670086	5	35	theme	resulting	815:823	arg1	structures					825:834	the resulting structures	811:834	the resulting structures	811:834	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	6	36	theme	unambiguous	992:1002	arg1	glycan					1013:1018	a single unambiguous O-linked glycan	983:1018	a single unambiguous O-linked glycan	983:1018	In the native-like trimer, we observe a single unambiguous O-linked glycan at T323, which displays very low occupancy.
34670086	7	37	theme	O-linked	1094:1101	arg1	glycosylation					1103:1115	O-linked glycosylation	1094:1115	O-linked glycosylation	1094:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	6	38	link	O-linked	1004:1011	arg1	glycan					1013:1018	a single unambiguous O-linked glycan	983:1018	a single unambiguous O-linked glycan	983:1018	In the native-like trimer, we observe a single unambiguous O-linked glycan at T323, which displays very low occupancy.
34670086	3	39	theme	protein	430:436	arg1	fragments					415:423	different recombinant fragments	393:423	different recombinant fragments of S protein	393:436	There is, therefore, potential for different recombinant fragments of S protein to display divergent glycosylation.
34670086	0	40	theme	Glycosylation	24:36	arg1	Suppression					0:10	Suppression	0:10	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.	0:97	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.
34670086	6	41	theme	single	985:990	arg1	glycan					1013:1018	a single unambiguous O-linked glycan	983:1018	a single unambiguous O-linked glycan	983:1018	In the native-like trimer, we observe a single unambiguous O-linked glycan at T323, which displays very low occupancy.
34670086	5	42	theme	O-linked	686:693	arg1	glycosylation					695:707	O-linked glycosylation	686:707	O-linked glycosylation	686:707	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	10	43	theme	protein	1715:1721	arg1	glycosylation					1688:1700	O-linked glycosylation	1679:1700	O-linked glycosylation of the spike protein	1679:1721	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	5	44	theme	electron-transfer	839:855	arg1	EThcD					895:899	EThcD	895:899	EThcD	895:899	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	5	44	theme	electron-transfer	839:855	arg1	dissociation					881:892	electron-transfer higher-energy collision dissociation	839:892	electron-transfer higher-energy collision dissociation (EThcD)	839:900	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	0	45	theme	O-Linked	15:22	arg1	Glycosylation					24:36	O-Linked Glycosylation	15:36	O-Linked Glycosylation of the SARS-CoV-2 Spike	15:60	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.
34670086	5	46	theme	Tribrid	925:931	arg1	instrument					933:942	Tribrid instrument	925:942	Tribrid instrument	925:942	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	5	47	theme	higher-energy	857:869	arg1	EThcD					895:899	EThcD	895:899	EThcD	895:899	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	5	47	theme	higher-energy	857:869	arg1	dissociation					881:892	electron-transfer higher-energy collision dissociation	839:892	electron-transfer higher-energy collision dissociation (EThcD)	839:900	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	5	48	theme	collision	871:879	arg1	EThcD					895:899	EThcD	895:899	EThcD	895:899	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	5	48	theme	collision	871:879	arg1	dissociation					881:892	electron-transfer higher-energy collision dissociation	839:892	electron-transfer higher-energy collision dissociation (EThcD)	839:900	We unambiguously assign O-linked glycosylation by homogenizing N-linked glycosylation using the enzymatic inhibitor, kifunensine, and then analyzing the resulting structures by electron-transfer higher-energy collision dissociation (EThcD) in an Orbitrap Eclipse Tribrid instrument.
34670086	10	49	link	O-linked	1679:1686	arg1	glycosylation					1688:1700	O-linked glycosylation	1679:1700	O-linked glycosylation of the spike protein	1679:1721	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	4	50	theme	trimeric	644:651	arg1	protein					653:659	the native-like soluble trimeric protein	620:659	the native-like soluble trimeric protein	620:659	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	3	51	theme	divergent	449:457	arg1	glycosylation					459:471	divergent glycosylation	449:471	divergent glycosylation	449:471	There is, therefore, potential for different recombinant fragments of S protein to display divergent glycosylation.
34670086	10	52	theme	matched	1609:1615	arg1	systems					1628:1634	matched expression systems	1609:1634	matched expression systems	1609:1634	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	9	53	theme	fragmentation	1373:1385	arg1	ions					1387:1390	fragmentation ions	1373:1390	fragmentation ions arising from trace levels of truncated N-linked glycans	1373:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	53	theme	fragmentation	1373:1385	arg1	structures					1504:1513	proximal putative O-linked glycan structures	1470:1513	proximal putative O-linked glycan structures	1470:1513	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	54	theme	glycans	1440:1446	arg1	levels					1411:1416	trace levels	1405:1416	trace levels of truncated N-linked glycans	1405:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	10	55	theme	expression	1617:1626	arg1	systems					1628:1634	matched expression systems	1609:1634	matched expression systems	1609:1634	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	8	56	theme	protein	1301:1307	arg1	architecture					1309:1320	quaternary protein architecture	1290:1320	quaternary protein architecture	1290:1320	We ascribe this effect to the relaxation of steric restraints arising from quaternary protein architecture.
34670086	1	57	theme	antigenic	208:216	arg1	surface					218:224	the antigenic surface	204:224	the antigenic surface of this key viral target	204:249	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
34670086	0	58	theme	Spike	56:60	arg1	Glycosylation					24:36	O-Linked Glycosylation	15:36	O-Linked Glycosylation of the SARS-CoV-2 Spike	15:60	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.
34670086	10	59	theme	O-linked	1679:1686	arg1	glycosylation					1688:1700	O-linked glycosylation	1679:1700	O-linked glycosylation of the spike protein	1679:1721	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	8	60	theme	quaternary	1290:1299	arg1	architecture					1309:1320	quaternary protein architecture	1290:1320	quaternary protein architecture	1290:1320	We ascribe this effect to the relaxation of steric restraints arising from quaternary protein architecture.
34670086	0	61	theme	SARS-CoV-2	45:54	arg1	Spike					56:60	the SARS-CoV-2 Spike	41:60	the SARS-CoV-2 Spike	41:60	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.
34670086	7	62	theme	several	1077:1083	arg1	glycosylation					1103:1115	O-linked glycosylation	1094:1115	O-linked glycosylation	1094:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	7	62	theme	several	1077:1083	arg1	sites					1085:1089	several sites	1077:1089	several sites of O-linked glycosylation	1077:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	4	63	link	O-linked	566:573	arg1	glycosylation					575:587	O-linked glycosylation	566:587	O-linked glycosylation	566:587	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	0	64	gly	Glycosylation	24:36	arg1	Spike					56:60	the SARS-CoV-2 Spike	41:60	the SARS-CoV-2 Spike	41:60	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.
34670086	7	65	link	O-linked	1094:1101	arg1	glycosylation					1103:1115	O-linked glycosylation	1094:1115	O-linked glycosylation	1094:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	6	66	theme	native-like	952:962	arg1	trimer					964:969	the native-like trimer	948:969	the native-like trimer	948:969	In the native-like trimer, we observe a single unambiguous O-linked glycan at T323, which displays very low occupancy.
34670086	9	67	theme	diagnostic	1548:1557	arg1	fragments					1559:1567	diagnostic fragments	1548:1567	diagnostic fragments	1548:1567	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	8	68	theme	restraints	1266:1275	arg1	relaxation					1245:1254	the relaxation	1241:1254	the relaxation of steric restraints arising from quaternary protein architecture	1241:1320	We ascribe this effect to the relaxation of steric restraints arising from quaternary protein architecture.
34670086	7	69	gly	glycosylation	1103:1115	arg2	sites					1085:1089	several sites	1077:1089	several sites of O-linked glycosylation	1077:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	7	69	gly	glycosylation	1103:1115	arg2	glycosylation					1103:1115	O-linked glycosylation	1094:1115	O-linked glycosylation	1094:1115	In contrast, several sites of O-linked glycosylation can be identified when RBD is expressed as a monomer, with T323 being almost completely occupied.
34670086	10	70	theme	spike	1709:1713	arg1	protein					1715:1721	the spike protein	1705:1721	the spike protein	1705:1721	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	2	71	theme	glycan	325:330	arg1	occupancy					332:340	glycan occupancy	325:340	glycan occupancy	325:340	However, the underlying protein architecture may significantly influence glycan occupancy and processing.
34670086	0	72	theme	Quaternary	65:74	arg1	Restraints					87:96	Quaternary Structural Restraints	65:96	Quaternary Structural Restraints	65:96	Suppression of O-Linked Glycosylation of the SARS-CoV-2 Spike by Quaternary Structural Restraints.
34670086	6	73	theme	low	1049:1051	arg1	occupancy					1053:1061	very low occupancy	1044:1061	very low occupancy	1044:1061	In the native-like trimer, we observe a single unambiguous O-linked glycan at T323, which displays very low occupancy.
34670086	10	74	theme	quaternary	1640:1649	arg1	architecture					1659:1670	the quaternary protein architecture	1636:1670	the quaternary protein architecture	1636:1670	Overall, we show that in matched expression systems the quaternary protein architecture limits O-linked glycosylation of the spike protein.
34670086	8	75	theme	steric	1259:1264	arg1	restraints					1266:1275	steric restraints	1259:1275	steric restraints arising from quaternary protein architecture	1259:1320	We ascribe this effect to the relaxation of steric restraints arising from quaternary protein architecture.
34670086	4	76	theme	native-like	624:634	arg1	protein					653:659	the native-like soluble trimeric protein	620:659	the native-like soluble trimeric protein	620:659	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	3	77	theme	different	393:401	arg1	fragments					415:423	different recombinant fragments	393:423	different recombinant fragments of S protein	393:436	There is, therefore, potential for different recombinant fragments of S protein to display divergent glycosylation.
34670086	4	78	theme	receptor	497:504	arg1	RBD					522:524	RBD	522:524	RBD	522:524	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	4	78	theme	receptor	497:504	arg1	domain					514:519	the receptor binding domain	493:519	the receptor binding domain (RBD)	493:525	Here, we show that the receptor binding domain (RBD), when expressed as a monomer, exhibits O-linked glycosylation, which is not recapitulated in the native-like soluble trimeric protein.
34670086	9	79	theme	truncated	1421:1429	arg1	glycans					1440:1446	truncated N-linked glycans	1421:1446	truncated N-linked glycans	1421:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	9	80	theme	trace	1405:1409	arg1	levels					1411:1416	trace levels	1405:1416	trace levels of truncated N-linked glycans	1405:1446	Our analytical approach has also highlighted that fragmentation ions arising from trace levels of truncated N-linked glycans can be misassigned as proximal putative O-linked glycan structures, particularly where a paucity of diagnostic fragments were obtained.
34670086	1	81	theme	key	234:236	arg1	target					244:249	this key viral target	229:249	this key viral target	229:249	Understanding the glycosylation of the envelope spike (S) protein of SARS-CoV-2 is important in defining the antigenic surface of this key viral target.
32462590	1	0	link	N-linked	105:112	arg1	modification					157:168	a ubiquitous posttranslational modification	126:168	a ubiquitous posttranslational modification	126:168	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	1	0	link	N-linked	105:112	arg1	glycans					114:120	N-linked glycans	105:120	N-linked glycans	105:120	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	5	1	theme	complementary	901:913	arg1	techniques					929:938	complementary fragmentation techniques	901:938	complementary fragmentation techniques	901:938	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	1	2	from	folding	208:214	arg1	reticulum					235:243	the endoplasmic reticulum	219:243	the endoplasmic reticulum of plants	219:253	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	5	3	theme	high	1069:1072	arg1	profile					1100:1106	an unbiased high confidence N-glycopeptide profile	1057:1106	an unbiased high confidence N-glycopeptide profile from plant samples	1057:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	4	theme	interaction	811:821	arg1	chromatography					823:836	hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples	799:1125	chromatography	823:836	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	1	5	theme	correct	192:198	arg1	folding					208:214	correct protein folding	192:214	correct protein folding in the endoplasmic reticulum of plants	192:253	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	5	6	theme	higher-energy	941:953	arg1	dissociation					967:978	higher-energy collisional dissociation	941:978	higher-energy collisional dissociation	941:978	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	7	theme	high-resolution	850:864	arg1	spectrometry					878:889	high-resolution tandem mass spectrometry	850:889	high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation)	850:1014	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	2	8	from	N-glycoproteins	382:396	arg1	plants					401:406	plants	401:406	plants	401:406	However, this likely represents a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants.
32462590	5	9	theme	analytics	1027:1035	arg1	workflow					1037:1044	a data analytics workflow	1020:1044	a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples	1020:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	10	theme	tandem	866:871	arg1	spectrometry					878:889	high-resolution tandem mass spectrometry	850:889	high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation)	850:1014	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	11	theme	N-glycopeptide	1085:1098	arg1	profile					1100:1106	an unbiased high confidence N-glycopeptide profile	1057:1106	an unbiased high confidence N-glycopeptide profile from plant samples	1057:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	3	12	gly	glycosylation	440:452	arg2	sites					454:458	N-linked glycosylation sites	431:458	N-linked glycosylation sites	431:458	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	1	13	theme	protein	200:206	arg1	folding					208:214	correct protein folding	192:214	correct protein folding in the endoplasmic reticulum of plants	192:253	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	5	14	theme	mass	873:876	arg1	spectrometry					878:889	high-resolution tandem mass spectrometry	850:889	high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation)	850:1014	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	15	theme	confidence	1074:1083	arg1	profile					1100:1106	an unbiased high confidence N-glycopeptide profile	1057:1106	an unbiased high confidence N-glycopeptide profile from plant samples	1057:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	2	16	theme	functional	297:306	arg1	role					308:311	a narrow functional role	288:311	a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants	288:406	However, this likely represents a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants.
32462590	3	17	theme	N-linked	431:438	arg1	sites					454:458	N-linked glycosylation sites	431:458	N-linked glycosylation sites	431:458	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	5	18	theme	fragmentation	915:927	arg1	techniques					929:938	complementary fragmentation techniques	901:938	complementary fragmentation techniques	901:938	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	4	19	gly	N-glycopeptides	723:737	arg2	N-glycopeptides					723:737	N-glycopeptides	723:737	N-glycopeptides	723:737	Current proteomic workflows are not optimized for the enrichment, identification and characterization of N-glycopeptides.
32462590	5	20	dep	chromatography	823:836	arg1	enrichment					838:847	enrichment	838:847	enrichment	838:847	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	1	21	theme	N-linked	105:112	arg1	modification					157:168	a ubiquitous posttranslational modification	126:168	a ubiquitous posttranslational modification	126:168	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	1	21	theme	N-linked	105:112	arg1	glycans					114:120	N-linked glycans	105:120	N-linked glycans	105:120	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	5	22	theme	analytical	768:777	arg1	procedure					779:787	a detailed analytical procedure	757:787	a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples	757:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	3	23	theme	glycosylation	440:452	arg1	sites					454:458	N-linked glycosylation sites	431:458	N-linked glycosylation sites	431:458	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	4	24	theme	proteomic	626:634	arg1	workflows					636:644	Current proteomic workflows	618:644	Current proteomic workflows	618:644	Current proteomic workflows are not optimized for the enrichment, identification and characterization of N-glycopeptides.
32462590	2	25	theme	glycan	338:343	arg1	structures					345:354	the diverse array of glycan structures	317:354	the diverse array of glycan structures currently associated with N-glycoproteins in plants	317:406	However, this likely represents a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants.
32462590	0	26	theme	Glycopeptides	23:35	arg1	Enrichment					0:9	Enrichment	0:9	Enrichment of N-Linked Glycopeptides	0:35	Enrichment of N-Linked Glycopeptides and Their Identification by Complementary Fragmentation Techniques.
32462590	0	26	theme	Glycopeptides	23:35	arg1	Identification					47:60	Their Identification	41:60	Their Identification by Complementary Fragmentation Techniques	41:102	Enrichment of N-Linked Glycopeptides and Their Identification by Complementary Fragmentation Techniques.
32462590	4	27	theme	Current	618:624	arg1	workflows					636:644	Current proteomic workflows	618:644	Current proteomic workflows	618:644	Current proteomic workflows are not optimized for the enrichment, identification and characterization of N-glycopeptides.
32462590	5	28	theme	hydrophilic	799:809	arg1	chromatography					823:836	hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples	799:1125	chromatography	823:836	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	2	29	theme	array of	329:336	arg1	structures					345:354	the diverse array of glycan structures	317:354	the diverse array of glycan structures currently associated with N-glycoproteins in plants	317:406	However, this likely represents a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants.
32462590	1	30	theme	endoplasmic	223:233	arg1	reticulum					235:243	the endoplasmic reticulum	219:243	the endoplasmic reticulum of plants	219:253	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	0	31	theme	N-Linked	14:21	arg1	Glycopeptides					23:35	N-Linked Glycopeptides	14:35	N-Linked Glycopeptides	14:35	Enrichment of N-Linked Glycopeptides and Their Identification by Complementary Fragmentation Techniques.
32462590	5	32	gly	N-glycopeptide	1085:1098	arg2	N-glycopeptide					1085:1098	an unbiased high confidence N-glycopeptide profile	1057:1106	an unbiased high confidence N-glycopeptide profile from plant samples	1057:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	2	33	theme	diverse	321:327	arg1	structures					345:354	the diverse array of glycan structures	317:354	the diverse array of glycan structures currently associated with N-glycoproteins in plants	317:406	However, this likely represents a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants.
32462590	3	34	theme	relative	558:565	arg1	abundance					567:575	relative abundance	558:575	relative abundance	558:575	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	5	35	dep	spectrometry	878:889	arg1	dissociation					967:978	higher-energy collisional dissociation	941:978	higher-energy collisional dissociation	941:978	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	35	dep	spectrometry	878:889	arg1	dissociation					1002:1013	electron-transfer dissociation	984:1013	electron-transfer dissociation	984:1013	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	3	36	theme	mass	501:504	arg1	spectrometry					506:517	mass spectrometry	501:517	mass spectrometry	501:517	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	3	37	theme	structural	470:479	arg1	characterization					481:496	their structural characterization	464:496	their structural characterization by mass spectrometry	464:517	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	5	38	theme	electron-transfer	984:1000	arg1	dissociation					1002:1013	electron-transfer dissociation	984:1013	electron-transfer dissociation	984:1013	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	39	theme	data	1022:1025	arg1	workflow					1037:1044	a data analytics workflow	1020:1044	a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples	1020:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	1	40	theme	plants	248:253	arg1	reticulum					235:243	the endoplasmic reticulum	219:243	the endoplasmic reticulum of plants	219:253	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	3	41	theme	sites	454:458	arg1	identification					413:426	The identification	409:426	The identification of N-linked glycosylation sites	409:458	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	3	41	theme	sites	454:458	arg1	characterization					481:496	their structural characterization	464:496	their structural characterization by mass spectrometry	464:517	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	5	42	theme	detailed	759:766	arg1	procedure					779:787	a detailed analytical procedure	757:787	a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples	757:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	1	43	theme	ubiquitous	128:137	arg1	modification					157:168	a ubiquitous posttranslational modification	126:168	a ubiquitous posttranslational modification	126:168	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	1	43	theme	ubiquitous	128:137	arg1	glycans					114:120	N-linked glycans	105:120	N-linked glycans	105:120	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	5	44	theme	collisional	955:965	arg1	dissociation					967:978	higher-energy collisional dissociation	941:978	higher-energy collisional dissociation	941:978	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	2	45	gly	N-glycoproteins	382:396	arg1	N-glycoproteins					382:396	N-glycoproteins	382:396	N-glycoproteins in plants	382:406	However, this likely represents a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants.
32462590	1	46	theme	posttranslational	139:155	arg1	modification					157:168	a ubiquitous posttranslational modification	126:168	a ubiquitous posttranslational modification	126:168	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	1	46	theme	posttranslational	139:155	arg1	glycans					114:120	N-linked glycans	105:120	N-linked glycans	105:120	N-linked glycans are a ubiquitous posttranslational modification and are essential for correct protein folding in the endoplasmic reticulum of plants.
32462590	2	47	theme	narrow	290:295	arg1	role					308:311	a narrow functional role	288:311	a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants	288:406	However, this likely represents a narrow functional role for the diverse array of glycan structures currently associated with N-glycoproteins in plants.
32462590	5	48	theme	plant	1113:1117	arg1	samples					1119:1125	plant samples	1113:1125	plant samples	1113:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	5	49	from	samples	1119:1125	arg1	profile					1100:1106	an unbiased high confidence N-glycopeptide profile	1057:1106	an unbiased high confidence N-glycopeptide profile from plant samples	1057:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
32462590	4	50	theme	enrichment	672:681	arg1	identification					684:697	identification	684:697	identification	684:697	Current proteomic workflows are not optimized for the enrichment, identification and characterization of N-glycopeptides.
32462590	0	51	theme	Fragmentation	79:91	arg1	Techniques					93:102	Complementary Fragmentation Techniques	65:102	Complementary Fragmentation Techniques	65:102	Enrichment of N-Linked Glycopeptides and Their Identification by Complementary Fragmentation Techniques.
32462590	4	52	theme	N-glycopeptides	723:737	arg1	characterization					703:718	characterization	703:718	characterization	703:718	Current proteomic workflows are not optimized for the enrichment, identification and characterization of N-glycopeptides.
32462590	4	52	theme	N-glycopeptides	723:737	arg1	identification					684:697	identification	684:697	identification	684:697	Current proteomic workflows are not optimized for the enrichment, identification and characterization of N-glycopeptides.
32462590	3	53	link	N-linked	431:438	arg1	sites					454:458	N-linked glycosylation sites	431:458	N-linked glycosylation sites	431:458	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	3	54	theme	structural	578:587	arg1	heterogeneity					589:601	structural heterogeneity	578:601	structural heterogeneity	578:601	The identification of N-linked glycosylation sites and their structural characterization by mass spectrometry remains challenging due to their size, relative abundance, structural heterogeneity, and polarity.
32462590	0	55	theme	Complementary	65:77	arg1	Techniques					93:102	Complementary Fragmentation Techniques	65:102	Complementary Fragmentation Techniques	65:102	Enrichment of N-Linked Glycopeptides and Their Identification by Complementary Fragmentation Techniques.
32462590	5	56	theme	unbiased	1060:1067	arg1	profile					1100:1106	an unbiased high confidence N-glycopeptide profile	1057:1106	an unbiased high confidence N-glycopeptide profile from plant samples	1057:1125	Here we describe a detailed analytical procedure employing hydrophilic interaction chromatography enrichment, high-resolution tandem mass spectrometry employing complementary fragmentation techniques (higher-energy collisional dissociation and electron-transfer dissociation) and a data analytics workflow to produce an unbiased high confidence N-glycopeptide profile from plant samples.
30397726	2	0	theme	yeasts	456:461	arg1	use					449:451	the use	445:451	the use of yeasts for the production of many biopharmaceuticals	445:507	However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals.
30397726	3	1	theme	proteins	682:689	arg1	pharmacokinetics					625:640	pharmacokinetics	625:640	pharmacokinetics	625:640	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	3	1	theme	proteins	682:689	arg1	pharmacodynamics					646:661	pharmacodynamics	646:661	pharmacodynamics	646:661	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	4	2	from	blood	851:855	arg1	protein					834:840	the therapeutic protein	818:840	the therapeutic protein from the blood	818:855	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	4	2	from	blood	851:855	arg1	clearance					805:813	rapid clearance	799:813	rapid clearance of the therapeutic protein from the blood	799:855	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	5	3	dep	highlights	871:880	arg1	reducing					982:989	reducing	982:989	reducing yeast-specific glycans	982:1012	This chapter highlights the efforts made so far regarding the glyco-engineering of N- and O-type glycosylation, removing or reducing yeast-specific glycans.
30397726	5	3	dep	highlights	871:880	arg1	removing					970:977	removing	970:977	removing	970:977	This chapter highlights the efforts made so far regarding the glyco-engineering of N- and O-type glycosylation, removing or reducing yeast-specific glycans.
30397726	8	4	dep	Abstract	1393:1400	arg1	Graphical					1383:1391	Graphical	1383:1391	Graphical	1383:1391	Graphical Abstract.
30397726	4	5	theme	hypermannosylated	708:724	arg1	structures					735:744	Yeasts' hypermannosylated glycosyl structures	700:744	Yeasts' hypermannosylated glycosyl structures in some cases	700:758	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	2	6	theme	biopharmaceuticals	490:507	arg1	production					471:480	the production	467:480	the production of many biopharmaceuticals	467:507	However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals.
30397726	1	7	theme	valuable	57:64	arg1	Yeasts					46:51	Yeasts	46:51	Yeasts	46:51	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	1	7	theme	valuable	57:64	arg1	hosts					66:70	valuable hosts	57:70	valuable hosts for recombinant protein production	57:105	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	2	8	theme	many	485:488	arg1	biopharmaceuticals					490:507	many biopharmaceuticals	485:507	many biopharmaceuticals	485:507	However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals.
30397726	1	9	theme	high	243:246	arg1	yield					259:263	a high space-time yield	241:263	a high space-time yield	241:263	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	3	10	contain	has	603:605	arg2	impact					615:620	a large impact	607:620	a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well	607:697	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	3	10	contain	has	603:605	arg1	it					600:601	it	600:601	it	600:601	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	5	11	theme	O-type	948:953	arg1	glycosylation					955:967	O-type glycosylation	948:967	O-type glycosylation	948:967	This chapter highlights the efforts made so far regarding the glyco-engineering of N- and O-type glycosylation, removing or reducing yeast-specific glycans.
30397726	2	12	theme	mammalian	368:376	arg1	cells					378:382	mammalian cells	368:382	mammalian cells	368:382	However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals.
30397726	3	13	from	impact	615:620	arg1	pharmacokinetics					625:640	pharmacokinetics	625:640	pharmacokinetics	625:640	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	3	13	from	impact	615:620	arg1	pharmacodynamics					646:661	pharmacodynamics	646:661	pharmacodynamics	646:661	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	7	14	theme	biopharmaceutical	1297:1313	arg1	manufacturing					1315:1327	biopharmaceutical manufacturing	1297:1327	biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology	1297:1380	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	4	15	from	structures	735:744	arg1	cases					754:758	some cases	749:758	some cases	749:758	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	1	16	theme	recombinant	76:86	arg1	production					96:105	recombinant protein production	76:105	recombinant protein production	76:105	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	7	17	theme	remaining	1158:1166	arg1	challenges					1168:1177	remaining challenges	1158:1177	remaining challenges	1158:1177	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	4	18	theme	protein	834:840	arg1	clearance					805:813	rapid clearance	799:813	rapid clearance of the therapeutic protein from the blood	799:855	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	1	19	theme	protein	88:94	arg1	production					96:105	recombinant protein production	76:105	recombinant protein production	76:105	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	2	20	theme	structures	419:428	arg1	type					397:400	the type	393:400	the type	393:400	However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals.
30397726	1	21	theme	space-time	248:257	arg1	yield					259:263	a high space-time yield	241:263	a high space-time yield	241:263	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	4	22	theme	therapeutic	822:832	arg1	protein					834:840	the therapeutic protein	818:840	the therapeutic protein from the blood	818:855	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	7	23	theme	many	1112:1115	arg1	years					1117:1121	many years	1112:1121	many years of patient development	1112:1144	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	2	24	theme	glycosylation	405:417	arg1	structures					419:428	glycosylation structures	405:428	glycosylation structures	405:428	However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals.
30397726	7	25	theme	biotechnology	1368:1380	arg1	days					1360:1363	the early days	1350:1363	the early days of biotechnology	1350:1380	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	1	26	theme	high	178:181	arg1	density					188:194	a high cell density	176:194	a high cell density on cost-effective defined media	176:226	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	0	27	theme	Yeast	15:19	arg1	Expression					34:43	Yeast Glycoprotein Expression	15:43	Yeast Glycoprotein Expression	15:43	Engineering of Yeast Glycoprotein Expression.
30397726	3	28	theme	large	609:613	arg1	impact					615:620	a large impact	607:620	a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well	607:697	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	4	29	theme	glycosyl	726:733	arg1	structures					735:744	Yeasts' hypermannosylated glycosyl structures	700:744	Yeasts' hypermannosylated glycosyl structures in some cases	700:758	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	1	30	theme	cell	183:186	arg1	density					188:194	a high cell density	176:194	a high cell density on cost-effective defined media	176:226	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	7	31	theme	patient	1126:1132	arg1	development					1134:1144	patient development	1126:1144	patient development	1126:1144	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	5	32	theme	N-	941:942	arg1	glyco-engineering					920:936	the glyco-engineering	916:936	the glyco-engineering of N- and O-type glycosylation	916:967	This chapter highlights the efforts made so far regarding the glyco-engineering of N- and O-type glycosylation, removing or reducing yeast-specific glycans.
30397726	5	33	theme	yeast-specific	991:1004	arg1	glycans					1006:1012	yeast-specific glycans	991:1012	yeast-specific glycans	991:1012	This chapter highlights the efforts made so far regarding the glyco-engineering of N- and O-type glycosylation, removing or reducing yeast-specific glycans.
30397726	7	34	theme	primary	1277:1283	arg1	position					1285:1292	the primary position	1273:1292	the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology	1273:1380	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	0	35	theme	Expression	34:43	arg1	Engineering					0:10	Engineering	0:10	Engineering of Yeast Glycoprotein Expression	0:43	Engineering of Yeast Glycoprotein Expression.
30397726	7	36	theme	development	1134:1144	arg1	years					1117:1121	many years	1112:1121	many years of patient development	1112:1144	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	0	37	theme	Glycoprotein	21:32	arg1	Expression					34:43	Yeast Glycoprotein Expression	15:43	Yeast Glycoprotein Expression	15:43	Engineering of Yeast Glycoprotein Expression.
30397726	1	38	from	density	188:194	arg1	media					222:226	cost-effective defined media	199:226	cost-effective defined media	199:226	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	3	39	theme	folding	554:560	arg1	process					562:568	the folding process	550:568	the folding process of most recombinant proteins	550:597	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	7	40	from	position	1285:1292	arg1	manufacturing					1315:1327	biopharmaceutical manufacturing	1297:1327	biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology	1297:1380	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	3	41	theme	therapeutic	670:680	arg1	proteins					682:689	the therapeutic proteins	666:689	the therapeutic proteins as well	666:697	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	4	42	theme	rapid	799:803	arg1	clearance					805:813	rapid clearance	799:813	rapid clearance of the therapeutic protein from the blood	799:855	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	1	43	theme	unicellular	117:127	arg1	eukaryotes					129:138	these unicellular eukaryotes	111:138	these unicellular eukaryotes	111:138	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	7	44	theme	early	1354:1358	arg1	days					1360:1363	the early days	1350:1363	the early days of biotechnology	1350:1380	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	4	45	theme	immune	770:775	arg1	responses					777:785	immune responses	770:785	immune responses	770:785	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	3	46	theme	most	573:576	arg1	proteins					590:597	most recombinant proteins	573:597	most recombinant proteins	573:597	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	1	47	theme	cost-effective	199:212	arg1	media					222:226	cost-effective defined media	199:226	cost-effective defined media	199:226	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	5	48	theme	glycosylation	955:967	arg1	glyco-engineering					920:936	the glyco-engineering	916:936	the glyco-engineering of N- and O-type glycosylation	916:967	This chapter highlights the efforts made so far regarding the glyco-engineering of N- and O-type glycosylation, removing or reducing yeast-specific glycans.
30397726	4	49	from	clearance	805:813	arg1	blood					851:855	the blood	847:855	the blood	847:855	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
30397726	6	50	theme	pathways	1096:1103	arg1	introduction					1056:1067	the introduction	1052:1067	the introduction of humanized glycosylation pathways	1052:1103	In some cases, this is combined with the introduction of humanized glycosylation pathways.
30397726	1	51	theme	defined	214:220	arg1	media					222:226	cost-effective defined media	199:226	cost-effective defined media	199:226	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	6	52	theme	humanized	1072:1080	arg1	pathways					1096:1103	humanized glycosylation pathways	1072:1103	humanized glycosylation pathways	1072:1103	In some cases, this is combined with the introduction of humanized glycosylation pathways.
30397726	3	53	theme	recombinant	578:588	arg1	proteins					590:597	most recombinant proteins	573:597	most recombinant proteins	573:597	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	6	54	theme	glycosylation	1082:1094	arg1	pathways					1096:1103	humanized glycosylation pathways	1072:1103	humanized glycosylation pathways	1072:1103	In some cases, this is combined with the introduction of humanized glycosylation pathways.
30397726	7	55	theme	effective	1217:1225	arg1	solutions					1227:1235	effective solutions	1217:1235	effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology	1217:1380	After many years of patient development to overcome remaining challenges, these efforts have now culminated in effective solutions that should allow yeasts to reclaim the primary position in biopharmaceutical manufacturing that they enjoyed in the early days of biotechnology.
30397726	1	56	theme	posttranslational	290:306	arg1	modifications					308:320	posttranslational modifications	290:320	posttranslational modifications	290:320	Yeasts are valuable hosts for recombinant protein production, as these unicellular eukaryotes are easy to handle, grow rapidly to a high cell density on cost-effective defined media, often offer a high space-time yield, and are able to perform posttranslational modifications.
30397726	3	57	theme	proteins	590:597	arg1	process					562:568	the folding process	550:568	the folding process of most recombinant proteins	550:597	Glycosylation is not only important for the folding process of most recombinant proteins; it has a large impact on pharmacokinetics and pharmacodynamics of the therapeutic proteins as well.
30397726	2	58	theme	key	334:336	arg1	difference					338:347	a key difference	332:347	a key difference between yeasts and mammalian cells	332:382	However, a key difference between yeasts and mammalian cells involves the type of glycosylation structures, which hampers the use of yeasts for the production of many biopharmaceuticals.
30397726	4	59	gly	hypermannosylated	708:724	arg1	structures					735:744	Yeasts' hypermannosylated glycosyl structures	700:744	Yeasts' hypermannosylated glycosyl structures in some cases	700:758	Yeasts' hypermannosylated glycosyl structures in some cases can evoke immune responses and lead to rapid clearance of the therapeutic protein from the blood.
33657946	7	0	theme	CONCLUSIONS	1252:1262	arg1	N-glycans					1271:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	7	0	theme	CONCLUSIONS	1252:1262	arg1	tool					1307:1310	a powerful prognostic tool	1285:1310	a powerful prognostic tool	1285:1310	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	6	1	theme	surgical	1188:1195	arg1	margins					1197:1203	positive surgical margins	1179:1203	positive surgical margins	1179:1203	Multivariate analysis proved positive surgical margins and 3AFc/MA to be independent prognosticators.
33657946	5	2	theme	structures	829:838	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	2	theme	structures	829:838	arg1	ratio					795:799	high ratio	790:799	high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	790:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	3	gly	fucosylated	804:814	arg1	structures					829:838	fucosylated triantennary structures	804:838	fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	804:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	6	4	theme	Multivariate	1150:1161	arg1	analysis					1163:1170	Multivariate analysis	1150:1170	Multivariate analysis	1150:1170	Multivariate analysis proved positive surgical margins and 3AFc/MA to be independent prognosticators.
33657946	5	5	from	ratio	1010:1014	arg1	total					1046:1050	total	1046:1050	total of multiantennary structures	1046:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	6	theme	total	843:847	arg1	[3AFc/MA					878:885	total of multiantennary structures [3AFc/MA	843:885	total of multiantennary structures [3AFc/MA	843:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	7	7	from	tool	1307:1310	arg1	PCa					1335:1337	PCa	1335:1337	PCa	1335:1337	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	7	8	theme	BCR-free	1396:1403	arg1	survival					1405:1412	BCR-free survival	1396:1412	BCR-free survival	1396:1412	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	4	9	theme	nodes	649:653	arg1	invasion					655:662	pelvic lymph nodes invasion	636:662	pelvic lymph nodes invasion (83%)	636:668	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	4	9	theme	nodes	649:653	arg1	%					667:667	83%	665:667	83%	665:667	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	5	10	theme	fucosylated	902:912	arg1	biantennary					914:924	fucosylated biantennary	902:924	fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures	902:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	11	theme	low	704:706	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	11	theme	low	704:706	arg1	score					716:720	low Gleason score	704:720	low Gleason score	704:720	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	12	theme	structures	1070:1079	arg1	total					1046:1050	total	1046:1050	total of multiantennary structures	1046:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	13	theme	fucosylated	804:814	arg1	structures					829:838	fucosylated triantennary structures	804:838	fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	804:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	8	14	theme	guiding	1448:1454	arg1	patients					1456:1463	guiding patients	1448:1463	guiding patients	1448:1463	This could be of clinical use in guiding patients following radical prostatectomy, e.g. referral to adjuvant radiotherapy.
33657946	6	15	theme	independent	1223:1233	arg1	prognosticators					1235:1249	independent prognosticators	1223:1249	independent prognosticators	1223:1249	Multivariate analysis proved positive surgical margins and 3AFc/MA to be independent prognosticators.
33657946	5	16	theme	triantennary	1019:1030	arg1	structures					1032:1041	triantennary structures	1019:1041	triantennary structures on total of multiantennary structures	1019:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	17	theme	biantennary	914:924	arg1	ratio					1010:1014	high ratio	1005:1014	high ratio of triantennary structures on total of multiantennary structures	1005:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	17	theme	biantennary	914:924	arg1	parameters					679:688	Several parameters	671:688	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA]	671:886	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	17	theme	biantennary	914:924	arg1	ratio					893:897	low ratio	889:897	low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures	889:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	18	theme	low	691:693	arg1	absence					752:758	absence	752:758	absence of positive surgical margins	752:787	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	18	theme	low	691:693	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	18	theme	low	691:693	arg1	groups					736:741	low EAU risk groups	723:741	low EAU risk groups for BCR	723:749	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	18	theme	low	691:693	arg1	score					716:720	low Gleason score	704:720	low Gleason score	704:720	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	18	theme	low	691:693	arg1	ratio					795:799	high ratio	790:799	high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	790:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	19	from	total	1046:1050	arg1	ratio					1010:1014	high ratio	1005:1014	high ratio of triantennary structures on total of multiantennary structures	1005:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	19	from	total	1046:1050	arg1	parameters					679:688	Several parameters	671:688	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA]	671:886	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	19	from	total	1046:1050	arg1	ratio					893:897	low ratio	889:897	low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures	889:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	20	theme	univariate	1099:1108	arg1	effect					1121:1126	a univariate beneficial effect	1097:1126	a univariate beneficial effect	1097:1126	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	21	theme	multiantennary	852:865	arg1	structures					867:876	multiantennary structures	852:876	multiantennary structures	852:876	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	3	22	theme	N-glycosylation	357:371	arg1	profile					373:379	Tissue N-glycosylation profile	350:379	Tissue N-glycosylation profile	350:379	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	5	23	from	structures	1032:1041	arg1	total					1046:1050	total	1046:1050	total of multiantennary structures	1046:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	24	gly	fucosylated	902:912	arg1	biantennary					914:924	fucosylated biantennary	902:924	fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures	902:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	4	25	theme	Gleason	567:573	arg1	disease					610:616	extensive local disease	594:616	extensive local disease (62%)	594:622	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	4	25	theme	Gleason	567:573	arg1	%					590:590	41%	588:590	41%	588:590	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	4	25	theme	Gleason	567:573	arg1	score					575:579	Gleason score 3 + 4	567:585	Gleason score 3 + 4 (41%)	567:591	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	3	26	theme	clinical	476:483	arg1	parameters					501:510	clinical and biochemical parameters	476:510	clinical and biochemical parameters for BCR-free survival	476:532	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	5	27	theme	low	723:725	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	27	theme	low	723:725	arg1	groups					736:741	low EAU risk groups	723:741	low EAU risk groups for BCR	723:749	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	9	28	theme	Further	1538:1544	arg1	elaboration					1546:1556	Further elaboration	1538:1556	Further elaboration of this biomarker	1538:1574	Further elaboration of this biomarker is warranted.
33657946	4	29	theme	RESULTS	535:541	arg1	Majority					543:550	RESULTS Majority	535:550	RESULTS Majority	535:550	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	0	30	theme	recurrence-free	80:94	arg1	survival					96:103	biochemical recurrence-free survival	68:103	biochemical recurrence-free survival	68:103	Tissue N-linked glycosylation as potential prognostic biomarker for biochemical recurrence-free survival.
33657946	5	31	theme	surgical	772:779	arg1	margins					781:787	positive surgical margins	763:787	positive surgical margins	763:787	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	1	32	theme	Only	114:117	arg1	biomarkers					123:132	PURPOSE Only few biomarkers	106:132	PURPOSE Only few biomarkers	106:132	PURPOSE Only few biomarkers have been evaluated for their prognostic value following radical prostatectomy.
33657946	4	33	theme	extensive	594:602	arg1	disease					610:616	extensive local disease	594:616	extensive local disease (62%)	594:622	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	4	33	theme	extensive	594:602	arg1	%					621:621	62%	619:621	62%	619:621	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	4	33	theme	extensive	594:602	arg1	score					575:579	Gleason score 3 + 4	567:585	Gleason score 3 + 4 (41%)	567:591	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	3	34	theme	biochemical	489:499	arg1	parameters					501:510	clinical and biochemical parameters	476:510	clinical and biochemical parameters for BCR-free survival	476:532	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	1	35	theme	radical	191:197	arg1	prostatectomy					199:211	radical prostatectomy	191:211	radical prostatectomy	191:211	PURPOSE Only few biomarkers have been evaluated for their prognostic value following radical prostatectomy.
33657946	5	36	theme	BCR-free	1131:1138	arg1	survival					1140:1147	BCR-free survival	1131:1147	BCR-free survival	1131:1147	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	0	37	theme	potential	33:41	arg1	biomarker					54:62	potential prognostic biomarker	33:62	potential prognostic biomarker for biochemical recurrence-free survival	33:103	Tissue N-linked glycosylation as potential prognostic biomarker for biochemical recurrence-free survival.
33657946	5	38	theme	high	1005:1008	arg1	ratio					1010:1014	high ratio	1005:1014	high ratio of triantennary structures on total of multiantennary structures	1005:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	39	theme	risk	731:734	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	39	theme	risk	731:734	arg1	groups					736:741	low EAU risk groups	723:741	low EAU risk groups for BCR	723:749	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	2	40	theme	tissue	229:234	arg1	N-glycosylation					236:250	tissue N-glycosylation	229:250	tissue N-glycosylation	229:250	We explored if tissue N-glycosylation shows prognostic properties for biochemical recurrence (BCR)-free survival.
33657946	5	41	theme	biantennary	977:987	arg1	structures					989:998	biantennary structures	977:998	biantennary structures	977:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	7	42	from	asset	1326:1330	arg1	PCa					1335:1337	PCa	1335:1337	PCa	1335:1337	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	7	43	theme	powerful	1287:1294	arg1	N-glycans					1271:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	7	43	theme	powerful	1287:1294	arg1	tool					1307:1310	a powerful prognostic tool	1285:1310	a powerful prognostic tool	1285:1310	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	8	44	theme	clinical	1432:1439	arg1	use					1441:1443	clinical use	1432:1443	clinical use in guiding patients	1432:1463	This could be of clinical use in guiding patients following radical prostatectomy, e.g. referral to adjuvant radiotherapy.
33657946	7	45	theme	Tissue	1264:1269	arg1	N-glycans					1271:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	7	45	theme	Tissue	1264:1269	arg1	tool					1307:1310	a powerful prognostic tool	1285:1310	a powerful prognostic tool	1285:1310	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	3	46	dep	MATERIALS	328:336	arg1	determined					385:394	determined	385:394	was determined from 82 prostate cancer (PCa) patients and prognostic features	381:457	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	5	47	from	N-acetylglucosamine	945:963	arg1	total					968:972	total	968:972	total	968:972	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	8	48	dep	referral	1503:1510	arg1	e.g.					1498:1501	e.g.	1498:1501	e.g.	1498:1501	This could be of clinical use in guiding patients following radical prostatectomy, e.g. referral to adjuvant radiotherapy.
33657946	0	49	link	N-linked	7:14	arg1	glycosylation					16:28	N-linked glycosylation	7:28	N-linked glycosylation	7:28	Tissue N-linked glycosylation as potential prognostic biomarker for biochemical recurrence-free survival.
33657946	6	50	theme	positive	1179:1186	arg1	margins					1197:1203	positive surgical margins	1179:1203	positive surgical margins	1179:1203	Multivariate analysis proved positive surgical margins and 3AFc/MA to be independent prognosticators.
33657946	2	51	theme	-free	312:316	arg1	survival					318:325	biochemical recurrence (BCR)-free survival	284:325	biochemical recurrence (BCR)-free survival	284:325	We explored if tissue N-glycosylation shows prognostic properties for biochemical recurrence (BCR)-free survival.
33657946	5	52	theme	triantennary	816:827	arg1	structures					829:838	fucosylated triantennary structures	804:838	fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	804:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	53	with	biantennary	914:924	arg1	N-acetylglucosamine					945:963	core-branched N-acetylglucosamine	931:963	core-branched N-acetylglucosamine on total of biantennary structures	931:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	8	54	from	use	1441:1443	arg1	patients					1456:1463	guiding patients	1448:1463	guiding patients	1448:1463	This could be of clinical use in guiding patients following radical prostatectomy, e.g. referral to adjuvant radiotherapy.
33657946	5	55	theme	T	695:695	arg1	absence					752:758	absence	752:758	absence of positive surgical margins	752:787	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	55	theme	T	695:695	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	55	theme	T	695:695	arg1	groups					736:741	low EAU risk groups	723:741	low EAU risk groups for BCR	723:749	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	55	theme	T	695:695	arg1	score					716:720	low Gleason score	704:720	low Gleason score	704:720	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	55	theme	T	695:695	arg1	ratio					795:799	high ratio	790:799	high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	790:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	56	theme	high	790:793	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	56	theme	high	790:793	arg1	ratio					795:799	high ratio	790:799	high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	790:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	4	57	theme	lymph	643:647	arg1	nodes					649:653	pelvic lymph nodes	636:653	pelvic lymph nodes invasion (83%)	636:668	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	5	58	theme	multiantennary	1055:1068	arg1	structures					1070:1079	multiantennary structures	1055:1079	multiantennary structures	1055:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	3	59	theme	prostate	404:411	arg1	PCa					421:423	PCa	421:423	PCa	421:423	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	3	59	theme	prostate	404:411	arg1	cancer					413:418	prostate cancer	404:418	82 prostate cancer (PCa) patients	401:433	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	5	60	theme	Several	671:677	arg1	parameters					679:688	Several parameters	671:688	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA]	671:886	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	2	61	theme	prognostic	258:267	arg1	properties					269:278	prognostic properties	258:278	prognostic properties for biochemical recurrence (BCR)-free survival	258:325	We explored if tissue N-glycosylation shows prognostic properties for biochemical recurrence (BCR)-free survival.
33657946	3	62	theme	Tissue	350:355	arg1	profile					373:379	Tissue N-glycosylation profile	350:379	Tissue N-glycosylation profile	350:379	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	8	63	theme	radical	1475:1481	arg1	prostatectomy					1483:1495	radical prostatectomy	1475:1495	radical prostatectomy	1475:1495	This could be of clinical use in guiding patients following radical prostatectomy, e.g. referral to adjuvant radiotherapy.
33657946	5	64	theme	structures	1032:1041	arg1	ratio					1010:1014	high ratio	1005:1014	high ratio of triantennary structures on total of multiantennary structures	1005:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	64	theme	structures	1032:1041	arg1	parameters					679:688	Several parameters	671:688	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA]	671:886	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	64	theme	structures	1032:1041	arg1	ratio					893:897	low ratio	889:897	low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures	889:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	65	from	ratio	795:799	arg1	[3AFc/MA					878:885	total of multiantennary structures [3AFc/MA	843:885	total of multiantennary structures [3AFc/MA	843:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	66	theme	low	889:891	arg1	ratio					893:897	low ratio	889:897	low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures	889:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	7	67	theme	3AFc/MA	1355:1361	arg1	ratio					1346:1350	the ratio	1342:1350	the ratio of 3AFc/MA	1342:1361	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	5	68	theme	EAU	727:729	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	68	theme	EAU	727:729	arg1	groups					736:741	low EAU risk groups	723:741	low EAU risk groups for BCR	723:749	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	69	contain	have	1092:1095	arg2	effect					1121:1126	a univariate beneficial effect	1097:1126	a univariate beneficial effect	1097:1126	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	69	contain	have	1092:1095	arg1	ratio					1010:1014	high ratio	1005:1014	high ratio of triantennary structures on total of multiantennary structures	1005:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	69	contain	have	1092:1095	arg1	parameters					679:688	Several parameters	671:688	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA]	671:886	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	69	contain	have	1092:1095	arg1	ratio					893:897	low ratio	889:897	low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures	889:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	70	theme	beneficial	1110:1119	arg1	effect					1121:1126	a univariate beneficial effect	1097:1126	a univariate beneficial effect	1097:1126	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	71	from	structures	829:838	arg1	[3AFc/MA					878:885	total of multiantennary structures [3AFc/MA	843:885	total of multiantennary structures [3AFc/MA	843:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	72	theme	structures	867:876	arg1	total					843:847	total	843:847	total	843:847	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	8	73	theme	adjuvant	1515:1522	arg1	radiotherapy					1524:1535	adjuvant radiotherapy	1515:1535	adjuvant radiotherapy	1515:1535	This could be of clinical use in guiding patients following radical prostatectomy, e.g. referral to adjuvant radiotherapy.
33657946	5	74	theme	Gleason	708:714	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	74	theme	Gleason	708:714	arg1	score					716:720	low Gleason score	704:720	low Gleason score	704:720	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	75	from	[3AFc/MA	878:885	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	75	from	[3AFc/MA	878:885	arg1	ratio					795:799	high ratio	790:799	high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	790:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	76	theme	core-branched	931:943	arg1	N-acetylglucosamine					945:963	core-branched N-acetylglucosamine	931:963	core-branched N-acetylglucosamine on total of biantennary structures	931:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	3	77	theme	cancer	413:418	arg1	patients					426:433	82 prostate cancer (PCa) patients	401:433	82 prostate cancer (PCa) patients	401:433	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	9	78	theme	biomarker	1566:1574	arg1	elaboration					1546:1556	Further elaboration	1538:1556	Further elaboration of this biomarker	1538:1574	Further elaboration of this biomarker is warranted.
33657946	5	79	dep	parameters	679:688	arg1	absence					752:758	absence	752:758	absence of positive surgical margins	752:787	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	79	dep	parameters	679:688	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	79	dep	parameters	679:688	arg1	groups					736:741	low EAU risk groups	723:741	low EAU risk groups for BCR	723:749	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	79	dep	parameters	679:688	arg1	score					716:720	low Gleason score	704:720	low Gleason score	704:720	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	79	dep	parameters	679:688	arg1	ratio					795:799	high ratio	790:799	high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA	790:885	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	80	theme	positive	763:770	arg1	margins					781:787	positive surgical margins	763:787	positive surgical margins	763:787	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	81	from	ratio	893:897	arg1	total					1046:1050	total	1046:1050	total of multiantennary structures	1046:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	1	82	theme	PURPOSE	106:112	arg1	biomarkers					123:132	PURPOSE Only few biomarkers	106:132	PURPOSE Only few biomarkers	106:132	PURPOSE Only few biomarkers have been evaluated for their prognostic value following radical prostatectomy.
33657946	5	83	theme	margins	781:787	arg1	absence					752:758	absence	752:758	absence of positive surgical margins	752:787	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	5	83	theme	margins	781:787	arg1	stage					697:701	low T stage	691:701	low T stage	691:701	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	1	84	theme	few	119:121	arg1	biomarkers					123:132	PURPOSE Only few biomarkers	106:132	PURPOSE Only few biomarkers	106:132	PURPOSE Only few biomarkers have been evaluated for their prognostic value following radical prostatectomy.
33657946	4	85	theme	local	604:608	arg1	disease					610:616	extensive local disease	594:616	extensive local disease (62%)	594:622	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	4	85	theme	local	604:608	arg1	%					621:621	62%	619:621	62%	619:621	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	4	85	theme	local	604:608	arg1	score					575:579	Gleason score 3 + 4	567:585	Gleason score 3 + 4 (41%)	567:591	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	3	86	theme	BCR-free	516:523	arg1	survival					525:532	BCR-free survival	516:532	BCR-free survival	516:532	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	0	87	theme	prognostic	43:52	arg1	biomarker					54:62	potential prognostic biomarker	33:62	potential prognostic biomarker for biochemical recurrence-free survival	33:103	Tissue N-linked glycosylation as potential prognostic biomarker for biochemical recurrence-free survival.
33657946	0	88	theme	biochemical	68:78	arg1	survival					96:103	biochemical recurrence-free survival	68:103	biochemical recurrence-free survival	68:103	Tissue N-linked glycosylation as potential prognostic biomarker for biochemical recurrence-free survival.
33657946	7	89	theme	prognostic	1296:1305	arg1	N-glycans					1271:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans	1252:1279	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	7	89	theme	prognostic	1296:1305	arg1	tool					1307:1310	a powerful prognostic tool	1285:1310	a powerful prognostic tool	1285:1310	CONCLUSIONS Tissue N-glycans are a powerful prognostic tool and can be an asset in PCa as the ratio of 3AFc/MA is independently associated with BCR-free survival.
33657946	3	90	theme	prognostic	439:448	arg1	features					450:457	prognostic features	439:457	prognostic features	439:457	MATERIALS AND METHODS Tissue N-glycosylation profile was determined from 82 prostate cancer (PCa) patients and prognostic features were compared to clinical and biochemical parameters for BCR-free survival.
33657946	1	91	theme	prognostic	164:173	arg1	value					175:179	their prognostic value	158:179	their prognostic value following radical prostatectomy	158:211	PURPOSE Only few biomarkers have been evaluated for their prognostic value following radical prostatectomy.
33657946	5	92	theme	structures	989:998	arg1	N-acetylglucosamine					945:963	core-branched N-acetylglucosamine	931:963	core-branched N-acetylglucosamine on total of biantennary structures	931:998	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33657946	4	93	theme	pelvic	636:641	arg1	nodes					649:653	pelvic lymph nodes	636:653	pelvic lymph nodes invasion (83%)	636:668	RESULTS Majority presented with Gleason score 3 + 4 (41%), extensive local disease (62%) and without pelvic lymph nodes invasion (83%).
33657946	0	94	theme	N-linked	7:14	arg1	glycosylation					16:28	N-linked glycosylation	7:28	N-linked glycosylation	7:28	Tissue N-linked glycosylation as potential prognostic biomarker for biochemical recurrence-free survival.
33657946	5	95	from	parameters	679:688	arg1	total					1046:1050	total	1046:1050	total of multiantennary structures	1046:1079	Several parameters (low T stage, low Gleason score, low EAU risk groups for BCR, absence of positive surgical margins, high ratio of fucosylated triantennary structures on total of multiantennary structures [3AFc/MA], low ratio of fucosylated biantennary with core-branched N-acetylglucosamine on total of biantennary structures, and high ratio of triantennary structures on total of multiantennary structures) proved to have a univariate beneficial effect on BCR-free survival.
33125238	3	0	theme	large-scale	542:552	arg1	synthesis					564:572	large-scale enzymatic synthesis	542:572	large-scale enzymatic synthesis	542:572	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	2	1	from	developments	209:220	arg1	glycochemistry					239:252	glycochemistry	239:252	glycochemistry	239:252	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	2	1	from	developments	209:220	arg1	glycoproteomics					259:273	glycoproteomics	259:273	glycoproteomics	259:273	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	2	1	from	developments	209:220	arg1	glycobiology					225:236	glycobiology	225:236	glycobiology	225:236	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	3	2	theme	enzymatic	554:562	arg1	synthesis					564:572	large-scale enzymatic synthesis	542:572	large-scale enzymatic synthesis	542:572	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	1	3	from	importance	65:74	arg1	function					137:144	function	137:144	function	137:144	The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently.
33125238	1	3	from	importance	65:74	arg1	structure					123:131	protein structure	115:131	protein structure	115:131	The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently.
33125238	3	4	theme	current	401:407	arg1	progress					409:416	the current progress	397:416	the current progress in glycoscience	397:432	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	2	5	theme	disease	327:333	arg1	progression					335:345	disease progression	327:345	disease progression	327:345	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	4	6	theme	medicines	846:854	arg1	understanding					755:767	our understanding	751:767	our understanding of the significance of glycosylation	751:804	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	4	6	theme	medicines	846:854	arg1	development					810:820	development	810:820	development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance	810:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	4	7	theme	significance	921:932	arg1	level					889:893	the next level	880:893	the next level of scientific and medical significance	880:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	1	8	theme	post-translational	79:96	arg1	glycosylation					98:110	post-translational glycosylation	79:110	post-translational glycosylation	79:110	The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently.
33125238	4	9	theme	medical	913:919	arg1	significance					921:932	scientific and medical significance	898:932	scientific and medical significance	898:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	1	10	theme	glycosylation	98:110	arg1	importance					65:74	The importance	61:74	The importance of post-translational glycosylation in protein structure and function	61:144	The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently.
33125238	0	11	theme	Carbohydrate	10:21	arg1	Chemistry					23:31	Synthetic Carbohydrate Chemistry	0:31	Synthetic Carbohydrate Chemistry	0:31	Synthetic Carbohydrate Chemistry and Translational Medicine.
33125238	2	12	theme	immune-response	351:365	arg1	signaling					367:375	immune-response signaling	351:375	immune-response signaling	351:375	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	0	13	theme	Synthetic	0:8	arg1	Chemistry					23:31	Synthetic Carbohydrate Chemistry	0:31	Synthetic Carbohydrate Chemistry	0:31	Synthetic Carbohydrate Chemistry and Translational Medicine.
33125238	1	14	theme	protein	115:121	arg1	structure					123:131	protein structure	115:131	protein structure	115:131	The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently.
33125238	3	15	theme	glycan	598:603	arg1	array					605:609	glycan array	598:609	glycan array	598:609	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	16	theme	programmable	504:515	arg1	development					583:593	the development	579:593	the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors	579:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	16	theme	programmable	504:515	arg1	introduction					488:499	the introduction	484:499	the introduction of programmable and automatic as well as large-scale enzymatic synthesis,	484:573	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	17	theme	glycosylation	612:624	arg1	probes					626:631	glycosylation probes	612:631	glycosylation probes	612:631	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	2	18	theme	relevant	315:322	arg1	field					289:293	the field	285:293	the field more manageable and relevant to disease progression and immune-response signaling	285:375	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	3	19	theme	array	605:609	arg1	development					583:593	the development	579:593	the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors	579:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	19	theme	array	605:609	arg1	introduction					488:499	the introduction	484:499	the introduction of programmable and automatic as well as large-scale enzymatic synthesis,	484:573	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	20	theme	synthesis	564:572	arg1	development					583:593	the development	579:593	the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors	579:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	20	theme	synthesis	564:572	arg1	introduction					488:499	the introduction	484:499	the introduction of programmable and automatic as well as large-scale enzymatic synthesis,	484:573	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	4	21	theme	novel	704:708	arg1	methodologies					710:722	methodologies	710:722	methodologies	710:722	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	0	22	theme	Translational	37:49	arg1	Medicine					51:58	Translational Medicine	37:58	Translational Medicine	37:58	Synthetic Carbohydrate Chemistry and Translational Medicine.
33125238	2	23	theme	latest	202:207	arg1	developments					209:220	The latest developments	198:220	The latest developments in glycobiology, glycochemistry, and glycoproteomics	198:273	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	3	24	theme	inhibitors	638:647	arg1	development					583:593	the development	579:593	the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors	579:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	24	theme	inhibitors	638:647	arg1	introduction					488:499	the introduction	484:499	the introduction of programmable and automatic as well as large-scale enzymatic synthesis,	484:573	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	25	from	progress	409:416	arg1	glycoscience					421:432	glycoscience	421:432	glycoscience	421:432	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	26	theme	probes	626:631	arg1	development					583:593	the development	579:593	the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors	579:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	26	theme	probes	626:631	arg1	introduction					488:499	the introduction	484:499	the introduction of programmable and automatic as well as large-scale enzymatic synthesis,	484:573	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	4	27	theme	significance	776:787	arg1	understanding					755:767	our understanding	751:767	our understanding of the significance of glycosylation	751:804	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	4	27	theme	significance	776:787	arg1	development					810:820	development	810:820	development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance	810:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	3	28	theme	new	449:451	arg1	methodologies					453:465	the new methodologies	445:465	the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors	445:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	4	29	theme	scientific	898:907	arg1	significance					921:932	scientific and medical significance	898:932	scientific and medical significance	898:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	3	30	theme	receptors	687:695	arg1	array					605:609	glycan array	598:609	glycan array	598:609	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	30	theme	receptors	687:695	arg1	probes					626:631	glycosylation probes	612:631	glycosylation probes	612:631	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	30	theme	receptors	687:695	arg1	inhibitors					638:647	inhibitors	638:647	inhibitors of carbohydrate-associated enzymes or receptors	638:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	4	31	dep	methodologies	710:722	arg1	These					698:702	These	698:702	These	698:702	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	3	32	theme	enzymes	676:682	arg1	array					605:609	glycan array	598:609	glycan array	598:609	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	32	theme	enzymes	676:682	arg1	probes					626:631	glycosylation probes	612:631	glycosylation probes	612:631	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	32	theme	enzymes	676:682	arg1	inhibitors					638:647	inhibitors	638:647	inhibitors of carbohydrate-associated enzymes or receptors	638:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	2	33	theme	manageable	300:309	arg1	field					289:293	the field	285:293	the field more manageable and relevant to disease progression and immune-response signaling	285:375	The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling.
33125238	3	34	theme	automatic	521:529	arg1	development					583:593	the development	579:593	the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors	579:695	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	3	34	theme	automatic	521:529	arg1	introduction					488:499	the introduction	484:499	the introduction of programmable and automatic as well as large-scale enzymatic synthesis,	484:573	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
33125238	4	35	theme	carbohydrate-derived	825:844	arg1	medicines					846:854	carbohydrate-derived medicines	825:854	carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance	825:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	1	36	theme	significant	157:167	arg1	relevance					178:186	significant clinical relevance	157:186	significant clinical relevance	157:186	The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently.
33125238	4	37	theme	glycosylation	792:804	arg1	significance					776:787	the significance	772:787	the significance of glycosylation	772:804	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	4	38	theme	next	884:887	arg1	level					889:893	the next level	880:893	the next level of scientific and medical significance	880:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	1	39	theme	clinical	169:176	arg1	relevance					178:186	significant clinical relevance	157:186	significant clinical relevance	157:186	The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently.
33125238	4	40	link	carbohydrate-derived	825:844	arg1	medicines					846:854	carbohydrate-derived medicines	825:854	carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance	825:932	These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
33125238	3	41	theme	carbohydrate-associated	652:674	arg1	enzymes					676:682	carbohydrate-associated enzymes	652:682	carbohydrate-associated enzymes	652:682	Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors.
32965048	9	0	theme	structure-diagnostic	1882:1901	arg1	ions					1950:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	Next, 146 linkage structures and 200 N-glycosites were confirmed with structure-diagnostic and GlcNAc-containing site-determining product ions, respectively.
32965048	7	1	dep	moieties	1582:1589	arg1	sequences/linkages					1621:1638	sequences/linkages	1621:1638	sequences/linkages	1621:1638	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	7	1	dep	moieties	1582:1589	arg1	compositions					1607:1618	monosaccharide compositions	1592:1618	monosaccharide compositions	1592:1618	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	1	2	from	positions	376:384	arg1	glycoforms					276:285	multiple glycoforms	267:285	multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions	267:384	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	1	3	theme	monosaccharide	302:315	arg1	compositions					317:328	different monosaccharide compositions	292:328	different monosaccharide compositions	292:328	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	9	4	theme	GlcNAc-containing	1907:1923	arg1	ions					1950:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	Next, 146 linkage structures and 200 N-glycosites were confirmed with structure-diagnostic and GlcNAc-containing site-determining product ions, respectively.
32965048	13	5	theme	pathological	2470:2481	arg1	states					2483:2488	physiological and pathological states	2452:2488	physiological and pathological states	2452:2488	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	1	6	theme	RATIONALE	144:152	arg1	N-glycosylation					154:168	RATIONALE N-glycosylation	144:168	RATIONALE N-glycosylation	144:168	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	9	7	theme	product	1942:1948	arg1	ions					1950:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	Next, 146 linkage structures and 200 N-glycosites were confirmed with structure-diagnostic and GlcNAc-containing site-determining product ions, respectively.
32965048	11	8	theme	same	2161:2164	arg1	subject					2166:2172	the same subject	2157:2172	the same subject	2157:2172	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	1	9	from	linkages	353:360	arg1	glycoforms					276:285	multiple glycoforms	267:285	multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions	267:384	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	1	10	theme	post-translational	204:221	arg1	modifications					223:235	the most common protein post-translational modifications	180:235	the most common protein post-translational modifications	180:235	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	5	11	theme	collisional	1010:1020	arg1	energies					1022:1029	stepped normalized collisional energies	991:1029	stepped normalized collisional energies	991:1029	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	6	12	theme	structure-diagnostic	1323:1342	arg1	ions					1352:1355	structure-diagnostic product ions	1323:1355	structure-diagnostic product ions from the N-glycan moieties	1323:1382	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	2	13	gly	N-glycopeptide	571:584	arg2	N-glycopeptide					571:584	the intact N-glycopeptide database search engine	560:607	the intact N-glycopeptide database search engine	560:607	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	11	14	theme	elution-abundance	2063:2079	arg1	patterns					2081:2088	The elution-abundance patterns	2059:2088	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject	2059:2172	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	11	14	theme	elution-abundance	2063:2079	arg1	stable					2190:2195	stable	2190:2195	stable	2190:2195	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	10	15	theme	UniProt	2041:2047	arg1	database					2049:2056	the current UniProt database	2029:2056	the current UniProt database	2029:2056	CONCLUSIONS We found 106 new N-glycosites not annotated in the current UniProt database.
32965048	13	16	gly	glycopeptide	2345:2356	arg2	glycopeptide					2345:2356	glycopeptide oxonium ion patterns	2345:2377	glycopeptide oxonium ion patterns	2345:2377	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	8	17	theme	N-glycopeptide	1658:1671	arg1	IDs					1673:1675	The 2986 intact N-glycopeptide IDs	1642:1675	The 2986 intact N-glycopeptide IDs	1642:1675	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	11	18	theme	oxonium	2123:2129	arg1	m/z					2137:2139	m/z 138 and 204	2137:2151	m/z 138 and 204	2137:2151	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	11	18	theme	oxonium	2123:2129	arg1	ions					2131:2134	urinary intact N-glycopeptide oxonium ions	2093:2134	urinary intact N-glycopeptide oxonium ions (m/z 138 and 204)	2093:2152	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	13	19	theme	physiological	2452:2464	arg1	states					2483:2488	physiological and pathological states	2452:2488	physiological and pathological states	2452:2488	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	5	20	dep	METHODS	836:842	arg1	performed					847:855	performed	847:855	performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level	847:1215	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	21	theme	N-glycan	1573:1580	arg1	moieties					1582:1589	the N-glycan moieties	1569:1589	the N-glycan moieties (monosaccharide compositions, sequences/linkages)	1569:1639	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	11	22	theme	intact	2101:2106	arg1	m/z					2137:2139	m/z 138 and 204	2137:2151	m/z 138 and 204	2137:2151	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	11	22	theme	intact	2101:2106	arg1	ions					2131:2134	urinary intact N-glycopeptide oxonium ions	2093:2134	urinary intact N-glycopeptide oxonium ions (m/z 138 and 204)	2093:2152	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	4	23	theme	human	823:827	arg1	urine					829:833	human urine	823:833	human urine	823:833	In this study, we report our structure-specific N-glycoproteomics study of human urine.
32965048	8	24	gly	N-glycosites	1741:1752	arg2	N-glycosites					1741:1752	419 N-glycosites	1737:1752	419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins	1737:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	8	24	gly	N-glycosites	1741:1752	arg1	backbones					1769:1777	450 peptide backbones	1757:1777	450 peptide backbones from 327 intact N-glycoproteins	1757:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	2	25	theme	N-glycopeptide	571:584	arg1	engine					602:607	the intact N-glycopeptide database search engine	560:607	the intact N-glycopeptide database search engine	560:607	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	8	26	theme	N-glycan	1706:1713	arg1	structures					1723:1732	754 putative N-glycan linkage structures	1693:1732	754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins	1693:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	7	27	theme	intact	1426:1431	arg1	N-glycopeptides					1433:1447	2986 intact N-glycopeptides	1421:1447	2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages)	1421:1639	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	10	28	gly	N-glycosites	1999:2010	arg2	N-glycosites					1999:2010	106 new N-glycosites	1991:2010	106 new N-glycosites not annotated in the current UniProt database	1991:2056	CONCLUSIONS We found 106 new N-glycosites not annotated in the current UniProt database.
32965048	3	29	theme	non-invasive	698:709	arg1	attention					683:691	attention	683:691	attention	683:691	Urine has recently gained increasing attention as a non-invasive source for disease marker discovery.
32965048	3	29	theme	non-invasive	698:709	arg1	source					711:716	a non-invasive source	696:716	a non-invasive source for disease marker discovery	696:745	Urine has recently gained increasing attention as a non-invasive source for disease marker discovery.
32965048	4	30	theme	structure-specific	777:794	arg1	study					814:818	our structure-specific N-glycoproteomics study	773:818	our structure-specific N-glycoproteomics study of human urine	773:833	In this study, we report our structure-specific N-glycoproteomics study of human urine.
32965048	0	31	theme	site-determining	88:103	arg1	ions					138:141	site-determining and structure-diagnostic product ions	88:141	site-determining and structure-diagnostic product ions	88:141	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	13	32	theme	ion	2366:2368	arg1	markers					2409:2415	distinguishing markers	2394:2415	distinguishing markers between individuals and/or between physiological and pathological states	2394:2488	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	13	32	theme	ion	2366:2368	arg1	patterns					2370:2377	glycopeptide oxonium ion patterns	2345:2377	glycopeptide oxonium ion patterns	2345:2377	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	1	33	theme	common	189:194	arg1	modifications					223:235	the most common protein post-translational modifications	180:235	the most common protein post-translational modifications	180:235	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	0	34	theme	structure-diagnostic	109:128	arg1	ions					138:141	site-determining and structure-diagnostic product ions	88:141	site-determining and structure-diagnostic product ions	88:141	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	2	35	theme	search	595:600	arg1	engine					602:607	the intact N-glycopeptide database search engine	560:607	the intact N-glycopeptide database search engine	560:607	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	8	36	gly	N-glycoproteins	1795:1809	arg1	N-glycoproteins					1795:1809	327 intact N-glycoproteins	1784:1809	327 intact N-glycoproteins	1784:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	2	37	theme	mass	530:533	arg1	MS/MS					549:553	MS/MS	549:553	MS/MS	549:553	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	2	37	theme	mass	530:533	arg1	spectrometry					535:546	state-of-the-art tandem mass spectrometry	506:546	state-of-the-art tandem mass spectrometry (MS/MS)	506:554	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	8	38	theme	peptide	1761:1767	arg1	backbones					1769:1777	450 peptide backbones	1757:1777	450 peptide backbones from 327 intact N-glycoproteins	1757:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	10	39	dep	CONCLUSIONS	1970:1980	arg1	found					1985:1989	found	1985:1989	found 106 new N-glycosites not annotated in the current UniProt database	1985:2056	CONCLUSIONS We found 106 new N-glycosites not annotated in the current UniProt database.
32965048	2	40	theme	structure-specific	440:457	arg1	N-glycan					459:466	a particular site- and structure-specific N-glycan	417:466	a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS)	417:554	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	5	41	theme	site-	1081:1085	arg1	characterization					1128:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization	1065:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome	1065:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	42	theme	acid	1532:1535	arg1	sequences					1537:1545	amino acid sequences	1526:1545	amino acid sequences	1526:1545	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	2	43	theme	state-of-the-art	506:521	arg1	MS/MS					549:553	MS/MS	549:553	MS/MS	549:553	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	2	43	theme	state-of-the-art	506:521	arg1	spectrometry					535:546	state-of-the-art tandem mass spectrometry	506:546	state-of-the-art tandem mass spectrometry (MS/MS)	506:554	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	9	44	theme	linkage	1822:1828	arg1	structures					1830:1839	146 linkage structures	1818:1839	146 linkage structures	1818:1839	Next, 146 linkage structures and 200 N-glycosites were confirmed with structure-diagnostic and GlcNAc-containing site-determining product ions, respectively.
32965048	0	45	theme	structure-specific	10:27	arg1	characterization					29:44	structure-specific characterization	10:44	structure-specific characterization	10:44	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	1	46	theme	glycosidic	342:351	arg1	linkages					353:360	glycosidic linkages	342:360	glycosidic linkages	342:360	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	1	47	with	complex	254:260	arg1	glycoforms					276:285	multiple glycoforms	267:285	multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions	267:384	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	5	48	theme	structure-specific	1091:1108	arg1	characterization					1128:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization	1065:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome	1065:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	0	49	theme	N-glycoproteome	67:81	arg1	Site-					0:4	Site-	0:4	Site-	0:4	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	0	49	theme	N-glycoproteome	67:81	arg1	characterization					29:44	structure-specific characterization	10:44	structure-specific characterization	10:44	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	5	50	theme	Hydrophilic	889:899	arg1	ZIC-HILIC					929:937	ZIC-HILIC	929:937	ZIC-HILIC	929:937	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	5	50	theme	Hydrophilic	889:899	arg1	chromatography					913:926	Hydrophilic Interaction chromatography	889:926	Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment	876:949	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	51	gly	N-glycopeptides	1433:1447	arg2	N-glycopeptides					1433:1447	2986 intact N-glycopeptides	1421:1447	2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages)	1421:1639	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	5	52	theme	intact	1189:1194	arg1	level					1211:1215	the intact N-glycopeptide level	1185:1215	the intact N-glycopeptide level	1185:1215	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	53	theme	peptide	1507:1513	arg1	backbones					1515:1523	the peptide backbones	1503:1523	the peptide backbones (amino acid sequences and N-glycosites)	1503:1563	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	3	54	theme	marker	730:735	arg1	discovery					737:745	disease marker discovery	722:745	disease marker discovery	722:745	Urine has recently gained increasing attention as a non-invasive source for disease marker discovery.
32965048	11	55	gly	N-glycopeptide	2108:2121	arg2	N-glycopeptide					2108:2121	urinary intact N-glycopeptide oxonium ions	2093:2134	urinary intact N-glycopeptide oxonium ions (m/z 138 and 204)	2093:2152	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	5	56	theme	chromatography	913:926	arg1	enrichment					940:949	Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment	876:949	Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment	876:949	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	1	57	theme	anomeric	367:374	arg1	positions					376:384	anomeric positions	367:384	anomeric positions	367:384	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	13	58	theme	glycopeptide	2345:2356	arg1	markers					2409:2415	distinguishing markers	2394:2415	distinguishing markers between individuals and/or between physiological and pathological states	2394:2488	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	13	58	theme	glycopeptide	2345:2356	arg1	patterns					2370:2377	glycopeptide oxonium ion patterns	2345:2377	glycopeptide oxonium ion patterns	2345:2377	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	6	59	theme	peptide	1302:1308	arg1	backbone					1310:1317	the GlcNAc-containing site-determining peptide backbone	1263:1317	the GlcNAc-containing site-determining peptide backbone	1263:1317	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	0	60	with	Site-	0:4	arg1	ions					138:141	site-determining and structure-diagnostic product ions	88:141	site-determining and structure-diagnostic product ions	88:141	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	5	61	theme	urinary	1158:1164	arg1	N-glycoproteome					1166:1180	the human urinary N-glycoproteome	1148:1180	the human urinary N-glycoproteome	1148:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	62	theme	structure	1477:1485	arg1	information					1487:1497	structure information	1477:1497	structure information	1477:1497	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	8	63	theme	intact	1651:1656	arg1	IDs					1673:1675	The 2986 intact N-glycopeptide IDs	1642:1675	The 2986 intact N-glycopeptide IDs	1642:1675	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	2	64	theme	site-	430:434	arg1	N-glycan					459:466	a particular site- and structure-specific N-glycan	417:466	a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS)	417:554	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	5	65	theme	stepped	991:997	arg1	energies					1022:1029	stepped normalized collisional energies	991:1029	stepped normalized collisional energies	991:1029	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	0	66	theme	urinary	59:65	arg1	N-glycoproteome					67:81	the human urinary N-glycoproteome	49:81	the human urinary N-glycoproteome	49:81	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	7	67	with	N-glycopeptides	1433:1447	arg1	site					1468:1471	comprehensive site	1454:1471	comprehensive site	1454:1471	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	7	67	with	N-glycopeptides	1433:1447	arg1	information					1487:1497	structure information	1477:1497	structure information	1477:1497	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	10	68	theme	new	1995:1997	arg1	N-glycosites					1999:2010	106 new N-glycosites	1991:2010	106 new N-glycosites not annotated in the current UniProt database	1991:2056	CONCLUSIONS We found 106 new N-glycosites not annotated in the current UniProt database.
32965048	1	69	theme	different	292:300	arg1	compositions					317:328	different monosaccharide compositions	292:328	different monosaccharide compositions	292:328	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	6	70	theme	ion	1248:1250	arg1	pairs					1252:1256	b/y product ion pairs	1236:1256	b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone	1236:1317	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	9	71	gly	N-glycosites	1849:1860	arg2	N-glycosites					1849:1860	200 N-glycosites	1845:1860	200 N-glycosites	1845:1860	Next, 146 linkage structures and 200 N-glycosites were confirmed with structure-diagnostic and GlcNAc-containing site-determining product ions, respectively.
32965048	10	72	theme	current	2033:2039	arg1	database					2049:2056	the current UniProt database	2029:2056	the current UniProt database	2029:2056	CONCLUSIONS We found 106 new N-glycosites not annotated in the current UniProt database.
32965048	9	73	theme	site-determining	1925:1940	arg1	ions					1950:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	structure-diagnostic and GlcNAc-containing site-determining product ions	1882:1953	Next, 146 linkage structures and 200 N-glycosites were confirmed with structure-diagnostic and GlcNAc-containing site-determining product ions, respectively.
32965048	6	74	theme	N-glycan	1366:1373	arg1	moieties					1375:1382	the N-glycan moieties	1362:1382	the N-glycan moieties	1362:1382	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	5	75	theme	normalized	999:1008	arg1	energies					1022:1029	stepped normalized collisional energies	991:1029	stepped normalized collisional energies	991:1029	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	1	76	theme	protein	196:202	arg1	modifications					223:235	the most common protein post-translational modifications	180:235	the most common protein post-translational modifications	180:235	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	0	77	theme	human	53:57	arg1	N-glycoproteome					67:81	the human urinary N-glycoproteome	49:81	the human urinary N-glycoproteome	49:81	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	1	78	from	sequences	331:339	arg1	glycoforms					276:285	multiple glycoforms	267:285	multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions	267:384	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	1	79	theme	modifications	223:235	arg1	modifications					223:235	the most common protein post-translational modifications	180:235	the most common protein post-translational modifications	180:235	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	1	79	theme	modifications	223:235	arg1	one					173:175	one	173:175	one	173:175	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	6	80	theme	product	1344:1350	arg1	ions					1352:1355	structure-diagnostic product ions	1323:1355	structure-diagnostic product ions from the N-glycan moieties	1323:1382	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	11	81	theme	urinary	2093:2099	arg1	m/z					2137:2139	m/z 138 and 204	2137:2151	m/z 138 and 204	2137:2151	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	11	81	theme	urinary	2093:2099	arg1	ions					2131:2134	urinary intact N-glycopeptide oxonium ions	2093:2134	urinary intact N-glycopeptide oxonium ions (m/z 138 and 204)	2093:2152	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	1	82	from	compositions	317:328	arg1	glycoforms					276:285	multiple glycoforms	267:285	multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions	267:384	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	7	83	gly	N-glycosites	1551:1562	arg2	N-glycosites					1551:1562	N-glycosites	1551:1562	N-glycosites	1551:1562	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	5	84	theme	GPSeeker	1036:1043	arg1	search					1054:1059	GPSeeker database search	1036:1059	GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome	1036:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	85	theme	monosaccharide	1592:1605	arg1	sequences/linkages					1621:1638	sequences/linkages	1621:1638	sequences/linkages	1621:1638	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	7	85	theme	monosaccharide	1592:1605	arg1	compositions					1607:1618	monosaccharide compositions	1592:1618	monosaccharide compositions	1592:1618	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	11	86	theme	ions	2131:2134	arg1	patterns					2081:2088	The elution-abundance patterns	2059:2088	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject	2059:2172	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	11	86	theme	ions	2131:2134	arg1	stable					2190:2195	stable	2190:2195	stable	2190:2195	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	5	87	theme	database	1045:1052	arg1	search					1054:1059	GPSeeker database search	1036:1059	GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome	1036:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	8	88	theme	putative	1697:1704	arg1	structures					1723:1732	754 putative N-glycan linkage structures	1693:1732	754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins	1693:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	4	89	theme	N-glycoproteomics	796:812	arg1	study					814:818	our structure-specific N-glycoproteomics study	773:818	our structure-specific N-glycoproteomics study of human urine	773:833	In this study, we report our structure-specific N-glycoproteomics study of human urine.
32965048	11	90	theme	N-glycopeptide	2108:2121	arg1	m/z					2137:2139	m/z 138 and 204	2137:2151	m/z 138 and 204	2137:2151	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	11	90	theme	N-glycopeptide	2108:2121	arg1	ions					2131:2134	urinary intact N-glycopeptide oxonium ions	2093:2134	urinary intact N-glycopeptide oxonium ions (m/z 138 and 204)	2093:2152	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	8	91	theme	linkage	1715:1721	arg1	structures					1723:1732	754 putative N-glycan linkage structures	1693:1732	754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins	1693:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	13	92	theme	distinguishing	2394:2407	arg1	markers					2409:2415	distinguishing markers	2394:2415	distinguishing markers between individuals and/or between physiological and pathological states	2394:2488	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	13	92	theme	distinguishing	2394:2407	arg1	patterns					2370:2377	glycopeptide oxonium ion patterns	2345:2377	glycopeptide oxonium ion patterns	2345:2377	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	2	93	theme	intact	564:569	arg1	engine					602:607	the intact N-glycopeptide database search engine	560:607	the intact N-glycopeptide database search engine	560:607	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	13	94	theme	oxonium	2358:2364	arg1	markers					2409:2415	distinguishing markers	2394:2415	distinguishing markers between individuals and/or between physiological and pathological states	2394:2488	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	13	94	theme	oxonium	2358:2364	arg1	patterns					2370:2377	glycopeptide oxonium ion patterns	2345:2377	glycopeptide oxonium ion patterns	2345:2377	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	0	95	theme	product	130:136	arg1	ions					138:141	site-determining and structure-diagnostic product ions	88:141	site-determining and structure-diagnostic product ions	88:141	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	5	96	theme	N-glycoproteomics	1110:1126	arg1	characterization					1128:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization	1065:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome	1065:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	6	97	theme	GlcNAc-containing	1267:1283	arg1	backbone					1310:1317	the GlcNAc-containing site-determining peptide backbone	1263:1317	the GlcNAc-containing site-determining peptide backbone	1263:1317	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	13	98	theme	interesting	2316:2326	arg1	possibility					2328:2338	an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states	2313:2488	an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states	2313:2488	The results implied an interesting possibility that glycopeptide oxonium ion patterns could serve as distinguishing markers between individuals and/or between physiological and pathological states.
32965048	6	99	theme	product	1240:1246	arg1	pairs					1252:1256	b/y product ion pairs	1236:1256	b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone	1236:1317	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	2	100	theme	database	586:593	arg1	engine					602:607	the intact N-glycopeptide database search engine	560:607	the intact N-glycopeptide database search engine	560:607	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	8	101	theme	backbones	1769:1777	arg1	N-glycosites					1741:1752	419 N-glycosites	1737:1752	419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins	1737:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	6	102	from	moieties	1375:1382	arg1	ions					1352:1355	structure-diagnostic product ions	1323:1355	structure-diagnostic product ions from the N-glycan moieties	1323:1382	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	6	102	from	moieties	1375:1382	arg1	pairs					1252:1256	b/y product ion pairs	1236:1256	b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone	1236:1317	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	5	103	theme	trypsin	857:863	arg1	digestion					865:873	trypsin digestion	857:873	trypsin digestion	857:873	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	8	104	from	N-glycosites	1741:1752	arg1	N-glycoproteins					1795:1809	327 intact N-glycoproteins	1784:1809	327 intact N-glycoproteins	1784:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	6	105	used	used	1231:1234	arg2	we					1228:1229	we	1228:1229	we	1228:1229	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	5	106	theme	comprehensive	1067:1079	arg1	characterization					1128:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization	1065:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome	1065:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	107	theme	amino	1526:1530	arg1	sequences					1537:1545	amino acid sequences	1526:1545	amino acid sequences	1526:1545	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	2	108	theme	tandem	523:528	arg1	MS/MS					549:553	MS/MS	549:553	MS/MS	549:553	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	2	108	theme	tandem	523:528	arg1	spectrometry					535:546	state-of-the-art tandem mass spectrometry	506:546	state-of-the-art tandem mass spectrometry (MS/MS)	506:554	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	4	109	theme	urine	829:833	arg1	study					814:818	our structure-specific N-glycoproteomics study	773:818	our structure-specific N-glycoproteomics study of human urine	773:833	In this study, we report our structure-specific N-glycoproteomics study of human urine.
32965048	11	110	theme	subject	2166:2172	arg1	patterns					2081:2088	The elution-abundance patterns	2059:2088	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject	2059:2172	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	11	110	theme	subject	2166:2172	arg1	stable					2190:2195	stable	2190:2195	stable	2190:2195	The elution-abundance patterns of urinary intact N-glycopeptide oxonium ions (m/z 138 and 204) of the same subject were temporally stable during the day and over 6 months.
32965048	7	111	dep	backbones	1515:1523	arg1	N-glycosites					1551:1562	N-glycosites	1551:1562	N-glycosites	1551:1562	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	7	111	dep	backbones	1515:1523	arg1	sequences					1537:1545	amino acid sequences	1526:1545	amino acid sequences	1526:1545	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	5	112	gly	N-glycopeptide	1196:1209	arg2	N-glycopeptide					1196:1209	the intact N-glycopeptide level	1185:1215	the intact N-glycopeptide level	1185:1215	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	5	113	with	HCD	982:984	arg1	energies					1022:1029	stepped normalized collisional energies	991:1029	stepped normalized collisional energies	991:1029	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	5	114	theme	Zwitterionic	876:887	arg1	enrichment					940:949	Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment	876:949	Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment	876:949	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	8	115	from	N-glycoproteins	1795:1809	arg1	N-glycosites					1741:1752	419 N-glycosites	1737:1752	419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins	1737:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	8	115	from	N-glycoproteins	1795:1809	arg1	backbones					1769:1777	450 peptide backbones	1757:1777	450 peptide backbones from 327 intact N-glycoproteins	1757:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	3	116	theme	disease	722:728	arg1	discovery					737:745	disease marker discovery	722:745	disease marker discovery	722:745	Urine has recently gained increasing attention as a non-invasive source for disease marker discovery.
32965048	0	117	with	characterization	29:44	arg1	ions					138:141	site-determining and structure-diagnostic product ions	88:141	site-determining and structure-diagnostic product ions	88:141	Site- and structure-specific characterization of the human urinary N-glycoproteome with site-determining and structure-diagnostic product ions.
32965048	5	118	theme	Interaction	901:911	arg1	ZIC-HILIC					929:937	ZIC-HILIC	929:937	ZIC-HILIC	929:937	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	5	118	theme	Interaction	901:911	arg1	chromatography					913:926	Hydrophilic Interaction chromatography	889:926	Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment	876:949	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	5	119	theme	N-glycopeptide	1196:1209	arg1	level					1211:1215	the intact N-glycopeptide level	1185:1215	the intact N-glycopeptide level	1185:1215	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	8	120	theme	intact	1788:1793	arg1	N-glycoproteins					1795:1809	327 intact N-glycoproteins	1784:1809	327 intact N-glycoproteins	1784:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	6	121	from	backbone	1310:1317	arg1	ions					1352:1355	structure-diagnostic product ions	1323:1355	structure-diagnostic product ions from the N-glycan moieties	1323:1382	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	6	121	from	backbone	1310:1317	arg1	pairs					1252:1256	b/y product ion pairs	1236:1256	b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone	1236:1317	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	5	122	theme	human	1152:1156	arg1	N-glycoproteome					1166:1180	the human urinary N-glycoproteome	1148:1180	the human urinary N-glycoproteome	1148:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	8	123	gly	N-glycopeptide	1658:1671	arg2	N-glycopeptide					1658:1671	The 2986 intact N-glycopeptide IDs	1642:1675	The 2986 intact N-glycopeptide IDs	1642:1675	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
32965048	6	124	theme	site-determining	1285:1300	arg1	backbone					1310:1317	the GlcNAc-containing site-determining peptide backbone	1263:1317	the GlcNAc-containing site-determining peptide backbone	1263:1317	For this, we used b/y product ion pairs from the GlcNAc-containing site-determining peptide backbone and structure-diagnostic product ions from the N-glycan moieties, respectively.
32965048	7	125	dep	RESULTS	1399:1405	arg1	identified					1410:1419	identified	1410:1419	identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages)	1410:1639	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	1	126	theme	multiple	267:274	arg1	glycoforms					276:285	multiple glycoforms	267:285	multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions	267:384	RATIONALE N-glycosylation is one of the most common protein post-translational modifications; it is extremely complex with multiple glycoforms from different monosaccharide compositions, sequences, glycosidic linkages, and anomeric positions.
32965048	5	127	theme	N-glycoproteome	1166:1180	arg1	characterization					1128:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization	1065:1143	a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome	1065:1180	METHODS We performed trypsin digestion, Zwitterionic Hydrophilic Interaction chromatography (ZIC-HILIC) enrichment, C18-RPLC/nano-ESI-MS/MS using HCD with stepped normalized collisional energies, and GPSeeker database search for a comprehensive site- and structure-specific N-glycoproteomics characterization of the human urinary N-glycoproteome at the intact N-glycopeptide level.
32965048	7	128	theme	comprehensive	1454:1466	arg1	site					1468:1471	comprehensive site	1454:1471	comprehensive site	1454:1471	RESULTS We identified 2986 intact N-glycopeptides with comprehensive site and structure information for the peptide backbones (amino acid sequences and N-glycosites) and the N-glycan moieties (monosaccharide compositions, sequences/linkages).
32965048	12	129	theme	different	2273:2281	arg1	subjects					2283:2290	different subjects	2273:2290	different subjects	2273:2290	These patterns are rather different among different subjects.
32965048	2	130	theme	particular	419:428	arg1	N-glycan					459:466	a particular site- and structure-specific N-glycan	417:466	a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS)	417:554	Each glycoform functions with a particular site- and structure-specific N-glycan that can be fully characterized using state-of-the-art tandem mass spectrometry (MS/MS) and the intact N-glycopeptide database search engine GPSeeker that we recently developed.
32965048	8	131	from	structures	1723:1732	arg1	N-glycosites					1741:1752	419 N-glycosites	1737:1752	419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins	1737:1809	The 2986 intact N-glycopeptide IDs corresponded to 754 putative N-glycan linkage structures on 419 N-glycosites of 450 peptide backbones from 327 intact N-glycoproteins.
34324829	6	0	theme	EndoBT-3987	1011:1021	arg1	structure					987:995	the X-ray crystal structure	969:995	the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product	969:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	7	1	theme	antibody	1268:1275	arg1	substrate					1277:1285	a chemically engineered monoclonal antibody substrate	1233:1285	a chemically engineered monoclonal antibody substrate	1233:1285	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	7	2	theme	molecular	1153:1161	arg1	calculations					1171:1182	molecular docking calculations	1153:1182	molecular docking calculations	1153:1182	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	3	3	theme	biology	571:577	arg1	understanding					554:566	our fundamental understanding	538:566	our fundamental understanding of biology	538:577	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	7	4	theme	docking	1163:1169	arg1	calculations					1171:1182	molecular docking calculations	1153:1182	molecular docking calculations	1153:1182	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	6	5	from	EndoBT-3987	1011:1021	arg1	complex					1060:1066	complex	1060:1066	complex with a hybrid-type glycan product	1060:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	6	6	theme	ENGase	1004:1009	arg1	EndoBT-3987					1011:1021	the ENGase EndoBT-3987	1000:1021	the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product	1000:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	1	7	theme	essential	191:199	arg1	stability					270:278	protein stability	262:278	protein stability	262:278	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	1	7	theme	essential	191:199	arg1	proteins					181:188	proteins	181:188	proteins	181:188	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	1	7	theme	essential	191:199	arg1	events					340:345	molecular recognition events	318:345	molecular recognition events	318:345	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	1	7	theme	essential	191:199	arg1	oligomerization					281:295	oligomerization	281:295	oligomerization	281:295	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	1	7	theme	essential	191:199	arg1	folding					253:259	protein folding	245:259	protein folding	245:259	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	8	8	gly	glycoproteins	1627:1639	arg1	glycoproteins					1627:1639	homogeneous N-glycan glycoproteins	1606:1639	homogeneous N-glycan glycoproteins	1606:1639	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	7	9	theme	hybrid-type	1313:1323	arg1	recognition					1325:1335	hybrid-type recognition	1313:1335	hybrid-type recognition	1313:1335	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	8	10	theme	N-glycan	1618:1625	arg1	glycoproteins					1627:1639	homogeneous N-glycan glycoproteins	1606:1639	homogeneous N-glycan glycoproteins	1606:1639	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	7	11	theme	engineered	1246:1255	arg1	antibody					1268:1275	a chemically engineered monoclonal antibody	1233:1275	a chemically engineered monoclonal antibody substrate	1233:1285	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	8	12	theme	chemoenzymatic	1563:1576	arg1	synthesis					1578:1586	synthesis	1578:1586	synthesis	1578:1586	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	6	13	theme	hybrid-type	1075:1085	arg1	product					1094:1100	a hybrid-type glycan product	1073:1100	a hybrid-type glycan product	1073:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	8	14	theme	recognition	1477:1487	arg1	mechanism					1454:1462	the molecular mechanism	1440:1462	the molecular mechanism of substrate recognition and specificity for GH18 ENGases	1440:1520	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	7	15	theme	monoclonal	1257:1266	arg1	antibody					1268:1275	a chemically engineered monoclonal antibody	1233:1275	a chemically engineered monoclonal antibody substrate	1233:1285	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	3	16	theme	new	611:613	arg1	drugs					615:619	new drugs	611:619	new drugs for a wide range of human diseases	611:654	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	2	17	theme	N-glycosylation	363:377	arg1	pathway					379:385	the N-glycosylation pathway	359:385	the N-glycosylation pathway	359:385	Defects in the N-glycosylation pathway cause diseases that are classified as congenital disorders of glycosylation.
34324829	5	18	theme	major	936:940	arg1	challenge					942:950	a major challenge	934:950	a major challenge	934:950	However, defining the molecular mechanisms by which ENGases specifically recognize and process N-glycans remains a major challenge.
34324829	2	19	theme	glycosylation	449:461	arg1	diseases					393:400	diseases	393:400	diseases that are classified as congenital disorders of glycosylation	393:461	Defects in the N-glycosylation pathway cause diseases that are classified as congenital disorders of glycosylation.
34324829	2	19	theme	glycosylation	449:461	arg1	disorders					436:444	congenital disorders	425:444	congenital disorders of glycosylation	425:461	Defects in the N-glycosylation pathway cause diseases that are classified as congenital disorders of glycosylation.
34324829	6	20	from	structure	987:995	arg1	complex					1060:1066	complex	1060:1066	complex with a hybrid-type glycan product	1060:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	6	20	from	structure	987:995	arg1	thetaiotaomicron					1040:1055	Bacteroides thetaiotaomicron	1028:1055	Bacteroides thetaiotaomicron	1028:1055	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	6	21	theme	crystal	979:985	arg1	structure					987:995	the X-ray crystal structure	969:995	the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product	969:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	1	22	theme	many	205:208	arg1	processes					224:232	many physiological processes	205:232	many physiological processes	205:232	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	6	23	theme	X-ray	973:977	arg1	structure					987:995	the X-ray crystal structure	969:995	the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product	969:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	8	24	theme	pivotal	1419:1425	arg1	insight					1427:1433	pivotal insight	1419:1433	pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases	1419:1520	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	1	25	theme	physiological	210:222	arg1	processes					224:232	many physiological processes	205:232	many physiological processes	205:232	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	0	26	theme	GH18	0:3	arg1	endo-β-N-acetylglucosaminidases					5:35	GH18 endo-β-N-acetylglucosaminidases	0:35	GH18 endo-β-N-acetylglucosaminidases	0:35	GH18 endo-β-N-acetylglucosaminidases use distinct mechanisms to process hybrid-type N-linked glycans.
34324829	6	27	theme	glycan	1087:1092	arg1	product					1094:1100	a hybrid-type glycan product	1073:1100	a hybrid-type glycan product	1073:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	4	28	theme	N-glycosylated	796:809	arg1	proteins					811:818	N-glycosylated proteins	796:818	N-glycosylated proteins	796:818	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases) has been used extensively to modulate the chemistry of N-glycosylated proteins.
34324829	3	29	theme	wide	627:630	arg1	range					632:636	a wide range	625:636	a wide range of human diseases	625:654	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	3	30	theme	protein	490:496	arg1	N-glycosylation					498:512	protein N-glycosylation	490:512	protein N-glycosylation	490:512	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	0	31	theme	distinct	41:48	arg1	mechanisms					50:59	distinct mechanisms	41:59	distinct mechanisms	41:59	GH18 endo-β-N-acetylglucosaminidases use distinct mechanisms to process hybrid-type N-linked glycans.
34324829	1	32	theme	molecular	318:326	arg1	events					340:345	molecular recognition events	318:345	molecular recognition events	318:345	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	7	33	theme	activity	1198:1205	arg1	measurements					1207:1218	enzymatic activity measurements	1188:1218	enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate	1188:1285	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	3	34	theme	drugs	615:619	arg1	development					596:606	the development	592:606	the development of new drugs for a wide range of human diseases	592:654	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	8	35	theme	remodeling	1592:1601	arg1	understanding					1546:1558	our understanding	1542:1558	our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins	1542:1639	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	1	36	theme	recognition	328:338	arg1	events					340:345	molecular recognition events	318:345	molecular recognition events	318:345	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	8	37	theme	GH18	1509:1512	arg1	ENGases					1514:1520	GH18 ENGases	1509:1520	GH18 ENGases	1509:1520	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	4	38	theme	engineered	688:697	arg1	ENGases					732:738	ENGases	732:738	ENGases	732:738	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases) has been used extensively to modulate the chemistry of N-glycosylated proteins.
34324829	4	38	theme	engineered	688:697	arg1	endo-β-N-acetylglucosaminidases					699:729	engineered endo-β-N-acetylglucosaminidases	688:729	engineered endo-β-N-acetylglucosaminidases (ENGases)	688:739	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases) has been used extensively to modulate the chemistry of N-glycosylated proteins.
34324829	4	39	gly	N-glycosylated	796:809	arg1	proteins					811:818	N-glycosylated proteins	796:818	N-glycosylated proteins	796:818	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases) has been used extensively to modulate the chemistry of N-glycosylated proteins.
34324829	3	40	theme	human	641:645	arg1	diseases					647:654	human diseases	641:654	human diseases	641:654	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	2	41	theme	congenital	425:434	arg1	diseases					393:400	diseases	393:400	diseases that are classified as congenital disorders of glycosylation	393:461	Defects in the N-glycosylation pathway cause diseases that are classified as congenital disorders of glycosylation.
34324829	2	41	theme	congenital	425:434	arg1	disorders					436:444	congenital disorders	425:444	congenital disorders of glycosylation	425:461	Defects in the N-glycosylation pathway cause diseases that are classified as congenital disorders of glycosylation.
34324829	1	42	theme	protein	245:251	arg1	folding					253:259	protein folding	245:259	protein folding	245:259	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	7	43	theme	enzymatic	1188:1196	arg1	measurements					1207:1218	enzymatic activity measurements	1188:1218	enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate	1188:1285	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	8	44	theme	specificity	1493:1503	arg1	mechanism					1454:1462	the molecular mechanism	1440:1462	the molecular mechanism of substrate recognition and specificity for GH18 ENGases	1440:1520	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	3	45	theme	diseases	647:654	arg1	range					632:636	a wide range	625:636	a wide range of human diseases	625:654	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	7	46	theme	scanning	1131:1138	arg1	mutagenesis					1140:1150	alanine scanning mutagenesis	1123:1150	alanine scanning mutagenesis	1123:1150	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	7	47	theme	paradigmatic	1355:1366	arg1	ENGases					1368:1374	paradigmatic ENGases	1355:1374	paradigmatic ENGases	1355:1374	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	0	48	theme	hybrid-type	72:82	arg1	glycans					93:99	hybrid-type N-linked glycans	72:99	hybrid-type N-linked glycans	72:99	GH18 endo-β-N-acetylglucosaminidases use distinct mechanisms to process hybrid-type N-linked glycans.
34324829	6	49	from	thetaiotaomicron	1040:1055	arg1	structure					987:995	the X-ray crystal structure	969:995	the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product	969:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	6	49	from	thetaiotaomicron	1040:1055	arg1	EndoBT-3987					1011:1021	the ENGase EndoBT-3987	1000:1021	the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product	1000:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	5	50	theme	molecular	843:851	arg1	mechanisms					853:862	the molecular mechanisms	839:862	the molecular mechanisms by which ENGases specifically recognize and process N-glycans	839:924	However, defining the molecular mechanisms by which ENGases specifically recognize and process N-glycans remains a major challenge.
34324829	8	51	theme	homogeneous	1606:1616	arg1	glycoproteins					1627:1639	homogeneous N-glycan glycoproteins	1606:1639	homogeneous N-glycan glycoproteins	1606:1639	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	4	52	used	used	750:753	arg2	synthesis					672:680	Chemoenzymatic synthesis	657:680	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases)	657:739	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases) has been used extensively to modulate the chemistry of N-glycosylated proteins.
34324829	8	53	theme	substrate	1467:1475	arg1	recognition					1477:1487	substrate recognition	1467:1487	substrate recognition	1467:1487	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	1	54	theme	abundant	137:144	arg1	modifications					164:176	the most abundant posttranslational modifications	128:176	the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events	128:345	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	6	55	theme	Bacteroides	1028:1038	arg1	thetaiotaomicron					1040:1055	Bacteroides thetaiotaomicron	1028:1055	Bacteroides thetaiotaomicron	1028:1055	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	6	56	from	complex	1060:1066	arg1	structure					987:995	the X-ray crystal structure	969:995	the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product	969:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	8	57	theme	glycoproteins	1627:1639	arg1	remodeling					1592:1601	remodeling	1592:1601	remodeling	1592:1601	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	8	57	theme	glycoproteins	1627:1639	arg1	synthesis					1578:1586	synthesis	1578:1586	synthesis	1578:1586	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	0	58	link	N-linked	84:91	arg1	glycans					93:99	hybrid-type N-linked glycans	72:99	hybrid-type N-linked glycans	72:99	GH18 endo-β-N-acetylglucosaminidases use distinct mechanisms to process hybrid-type N-linked glycans.
34324829	1	59	theme	posttranslational	146:162	arg1	modifications					164:176	the most abundant posttranslational modifications	128:176	the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events	128:345	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	6	60	with	complex	1060:1066	arg1	product					1094:1100	a hybrid-type glycan product	1073:1100	a hybrid-type glycan product	1073:1100	Here we present the X-ray crystal structure of the ENGase EndoBT-3987 from Bacteroides thetaiotaomicron in complex with a hybrid-type glycan product.
34324829	4	61	theme	Chemoenzymatic	657:670	arg1	synthesis					672:680	Chemoenzymatic synthesis	657:680	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases)	657:739	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases) has been used extensively to modulate the chemistry of N-glycosylated proteins.
34324829	7	62	theme	alanine	1123:1129	arg1	mutagenesis					1140:1150	alanine scanning mutagenesis	1123:1150	alanine scanning mutagenesis	1123:1150	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
34324829	4	63	theme	proteins	811:818	arg1	chemistry					783:791	the chemistry	779:791	the chemistry of N-glycosylated proteins	779:818	Chemoenzymatic synthesis using engineered endo-β-N-acetylglucosaminidases (ENGases) has been used extensively to modulate the chemistry of N-glycosylated proteins.
34324829	1	64	theme	modifications	164:176	arg1	one					121:123	one	121:123	one	121:123	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	1	64	theme	modifications	164:176	arg1	modifications					164:176	the most abundant posttranslational modifications	128:176	the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events	128:345	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	8	65	theme	experimental	1393:1404	arg1	data					1406:1409	the experimental data	1389:1409	the experimental data	1389:1409	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	1	66	theme	protein	262:268	arg1	stability					270:278	protein stability	262:278	protein stability	262:278	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	8	67	theme	synthesis	1578:1586	arg1	understanding					1546:1558	our understanding	1542:1558	our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins	1542:1639	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	8	68	theme	molecular	1444:1452	arg1	mechanism					1454:1462	the molecular mechanism	1440:1462	the molecular mechanism of substrate recognition and specificity for GH18 ENGases	1440:1520	Altogether, the experimental data provide pivotal insight into the molecular mechanism of substrate recognition and specificity for GH18 ENGases and further advance our understanding of chemoenzymatic synthesis and remodeling of homogeneous N-glycan glycoproteins.
34324829	3	69	theme	fundamental	542:552	arg1	understanding					554:566	our fundamental understanding	538:566	our fundamental understanding of biology	538:577	The ability to manipulate protein N-glycosylation is critical not only to our fundamental understanding of biology but also for the development of new drugs for a wide range of human diseases.
34324829	0	70	theme	N-linked	84:91	arg1	glycans					93:99	hybrid-type N-linked glycans	72:99	hybrid-type N-linked glycans	72:99	GH18 endo-β-N-acetylglucosaminidases use distinct mechanisms to process hybrid-type N-linked glycans.
34324829	1	71	theme	proteins	181:188	arg1	modifications					164:176	the most abundant posttranslational modifications	128:176	the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events	128:345	N-glycosylation is one of the most abundant posttranslational modifications of proteins, essential for many physiological processes, including protein folding, protein stability, oligomerization and aggregation, and molecular recognition events.
34324829	2	72	from	Defects	348:354	arg1	pathway					379:385	the N-glycosylation pathway	359:385	the N-glycosylation pathway	359:385	Defects in the N-glycosylation pathway cause diseases that are classified as congenital disorders of glycosylation.
34324829	7	73	with	combination	1106:1116	arg1	mutagenesis					1140:1150	alanine scanning mutagenesis	1123:1150	alanine scanning mutagenesis	1123:1150	In combination with alanine scanning mutagenesis, molecular docking calculations and enzymatic activity measurements conducted on a chemically engineered monoclonal antibody substrate unveil two mechanisms for hybrid-type recognition and processing by paradigmatic ENGases.
33453284	2	0	dep	antigens	293:300	arg1	e.g.					265:268	e.g.	265:268	e.g.	265:268	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	3	1	from	enzyme	508:513	arg1	synthesis					527:535	antennae synthesis	518:535	antennae synthesis	518:535	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	2	2	theme	cell	342:345	arg1	adherence					347:355	cell adherence	342:355	cell adherence	342:355	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	4	3	theme	other	585:589	arg1	members					591:597	other members	585:597	other members of GT31, the single largest human glycosyltransferase family	585:658	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	4	4	theme	GT31	602:605	arg1	members					591:597	other members	585:597	other members of GT31, the single largest human glycosyltransferase family	585:658	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	2	5	theme	cell-surface	280:291	arg1	modifications					250:262	diverse additional modifications	231:262	diverse additional modifications (e.g., terminal cell-surface antigens)	231:301	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	2	5	theme	cell-surface	280:291	arg1	antigens					293:300	terminal cell-surface antigens	271:300	terminal cell-surface antigens	271:300	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	4	6	theme	human	627:631	arg1	family					653:658	the single largest human glycosyltransferase family	608:658	the single largest human glycosyltransferase family	608:658	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	4	6	theme	human	627:631	arg1	GT31					602:605	GT31	602:605	GT31	602:605	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	1	7	theme	elongated	51:59	arg1	antennae					61:68	The elongated antennae	47:68	The elongated antennae decorating eukaryotic glycans	47:98	The elongated antennae decorating eukaryotic glycans are built from polylactosamine repeats.
33453284	3	8	theme	structural	419:428	arg1	investigation					446:458	a detailed structural and mechanistic investigation	408:458	a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2	408:499	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	3	8	theme	structural	419:428	arg1	enzyme					508:513	a key enzyme	502:513	a key enzyme in antennae synthesis	502:535	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	1	9	theme	eukaryotic	81:90	arg1	glycans					92:98	eukaryotic glycans	81:98	eukaryotic glycans	81:98	The elongated antennae decorating eukaryotic glycans are built from polylactosamine repeats.
33453284	3	10	theme	detailed	410:417	arg1	investigation					446:458	a detailed structural and mechanistic investigation	408:458	a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2	408:499	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	3	10	theme	detailed	410:417	arg1	enzyme					508:513	a key enzyme	502:513	a key enzyme in antennae synthesis	502:535	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	0	11	theme	your	14:17	arg1	antennae					37:44	your (polylactosamine) antennae	14:44	your (polylactosamine) antennae	14:44	How to extend your (polylactosamine) antennae.
33453284	4	12	theme	glycosyltransferase	633:651	arg1	family					653:658	the single largest human glycosyltransferase family	608:658	the single largest human glycosyltransferase family	608:658	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	4	12	theme	glycosyltransferase	633:651	arg1	GT31					602:605	GT31	602:605	GT31	602:605	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	2	13	theme	terminal	271:278	arg1	modifications					250:262	diverse additional modifications	231:262	diverse additional modifications (e.g., terminal cell-surface antigens)	231:301	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	2	13	theme	terminal	271:278	arg1	antigens					293:300	terminal cell-surface antigens	271:300	terminal cell-surface antigens	271:300	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	3	14	theme	β1-3-N-acetylgucosaminyltransferase	463:497	arg1	investigation					446:458	a detailed structural and mechanistic investigation	408:458	a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2	408:499	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	3	14	theme	β1-3-N-acetylgucosaminyltransferase	463:497	arg1	enzyme					508:513	a key enzyme	502:513	a key enzyme in antennae synthesis	502:535	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	0	15	theme	polylactosamine	20:34	arg1	antennae					37:44	your (polylactosamine) antennae	14:44	your (polylactosamine) antennae	14:44	How to extend your (polylactosamine) antennae.
33453284	2	16	theme	diverse	231:237	arg1	modifications					250:262	diverse additional modifications	231:262	diverse additional modifications (e.g., terminal cell-surface antigens)	231:301	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	2	16	theme	diverse	231:237	arg1	antigens					293:300	terminal cell-surface antigens	271:300	terminal cell-surface antigens	271:300	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	3	17	theme	mechanistic	434:444	arg1	investigation					446:458	a detailed structural and mechanistic investigation	408:458	a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2	408:499	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	3	17	theme	mechanistic	434:444	arg1	enzyme					508:513	a key enzyme	502:513	a key enzyme in antennae synthesis	502:535	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	2	18	theme	recognition	171:181	arg1	site					183:186	a lectin recognition site	162:186	a lectin recognition site	162:186	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	2	19	theme	lectin	164:169	arg1	site					183:186	a lectin recognition site	162:186	a lectin recognition site	162:186	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	3	20	theme	new	389:391	arg1	papers					393:398	Two new papers	385:398	Two new papers	385:398	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	3	21	theme	key	504:506	arg1	investigation					446:458	a detailed structural and mechanistic investigation	408:458	a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2	408:499	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	3	21	theme	key	504:506	arg1	enzyme					508:513	a key enzyme	502:513	a key enzyme in antennae synthesis	502:535	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	4	22	theme	resulting	542:550	arg1	insights					552:559	The resulting insights	538:559	The resulting insights	538:559	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	1	23	theme	polylactosamine	115:129	arg1	repeats					131:137	polylactosamine repeats	115:137	polylactosamine repeats	115:137	The elongated antennae decorating eukaryotic glycans are built from polylactosamine repeats.
33453284	2	24	theme	important	323:331	arg1	roles					333:337	important roles	323:337	important roles	323:337	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	3	25	theme	antennae	518:525	arg1	synthesis					527:535	antennae synthesis	518:535	antennae synthesis	518:535	Two new papers present a detailed structural and mechanistic investigation of β1-3-N-acetylgucosaminyltransferase 2, a key enzyme in antennae synthesis.
33453284	4	26	theme	largest	619:625	arg1	family					653:658	the single largest human glycosyltransferase family	608:658	the single largest human glycosyltransferase family	608:658	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	4	26	theme	largest	619:625	arg1	GT31					602:605	GT31	602:605	GT31	602:605	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	2	27	theme	additional	239:248	arg1	modifications					250:262	diverse additional modifications	231:262	diverse additional modifications (e.g., terminal cell-surface antigens)	231:301	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	2	27	theme	additional	239:248	arg1	antigens					293:300	terminal cell-surface antigens	271:300	terminal cell-surface antigens	271:300	Polylactosamine forms a lectin recognition site and also acts as a platform for presenting diverse additional modifications (e.g., terminal cell-surface antigens); it therefore plays important roles in cell adherence, development, and immunity.
33453284	4	28	theme	single	612:617	arg1	family					653:658	the single largest human glycosyltransferase family	608:658	the single largest human glycosyltransferase family	608:658	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
33453284	4	28	theme	single	612:617	arg1	GT31					602:605	GT31	602:605	GT31	602:605	The resulting insights will also help decipher other members of GT31, the single largest human glycosyltransferase family.
32817340	8	0	dep	M.	1722:1723	arg1	thermolithotrophicus					1725:1744	thermolithotrophicus	1725:1744	thermolithotrophicus	1725:1744	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	4	1	from	characterization	695:710	arg1	archaellins					756:766	archaellins	756:766	archaellins	756:766	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	1	from	characterization	695:710	arg1	protein					780:786	S-layer protein	772:786	S-layer protein	772:786	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	8	2	link	N-linked	1757:1764	arg1	larger					1776:1781	larger	1776:1781	larger	1776:1781	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	2	link	N-linked	1757:1764	arg1	glycan					1766:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	7	3	mod	modified	1631:1638	arg1	protein					1620:1626	the S-layer protein	1608:1626	the S-layer protein	1608:1626	In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway.
32817340	7	3	mod	modified	1631:1638	arg3	glycan					1665:1670	the same heptameric glycan	1645:1670	the same heptameric glycan	1645:1670	In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway.
32817340	4	4	dep	branched	1048:1055	arg1	heptameric					1058:1067	heptameric	1058:1067	heptameric	1058:1067	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	6	5	theme	glycan	1503:1508	arg1	variants					1510:1517	several, less abundant glycan variants	1480:1517	several, less abundant glycan variants	1480:1517	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	4	6	theme	MS	890:891	arg1	analysis					893:900	MS analysis	890:900	MS analysis	890:900	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	8	7	theme	methanogens	1874:1884	arg1	archaellins					1840:1850	the archaellins	1836:1850	the archaellins of related mesophilic methanogens	1836:1884	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	7	theme	methanogens	1874:1884	arg1	voltae					1901:1906	Methanococcus voltae	1887:1906	Methanococcus voltae	1887:1906	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	7	theme	methanogens	1874:1884	arg1	maripaludis					1926:1936	Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures	1912:2073	Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures	1912:2073	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	2	8	theme	subsequent	321:330	arg1	incorporation					332:344	their subsequent incorporation	315:344	their subsequent incorporation into the archaellum filament	315:373	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	1	9	theme	unique	195:200	arg1	structure					202:210	a unique structure	193:210	a unique structure termed the archaellum	193:232	Motility in archaea is facilitated by a unique structure termed the archaellum.
32817340	0	10	link	N-linked	26:33	arg1	glycan					35:40	a novel N-linked glycan	18:40	a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus	18:152	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	8	11	theme	Methanococcus	1887:1899	arg1	archaellins					1840:1850	the archaellins	1836:1850	the archaellins of related mesophilic methanogens	1836:1884	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	11	theme	Methanococcus	1887:1899	arg1	voltae					1901:1906	Methanococcus voltae	1887:1906	Methanococcus voltae	1887:1906	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	6	12	theme	several	1480:1486	arg1	variants					1510:1517	several, less abundant glycan variants	1480:1517	several, less abundant glycan variants	1480:1517	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	6	13	from	glycan	1569:1574	arg1	distinct					1535:1542	distinct	1535:1542	distinct	1535:1542	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	6	14	theme	interaction	1412:1422	arg1	chromatography-MS					1435:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	4	15	theme	closest	1120:1126	arg1	site					1115:1118	the site	1111:1118	the site closest to the N termini of both proteins	1111:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	6	16	theme	detailed	1374:1381	arg1	investigation					1383:1395	A detailed investigation	1372:1395	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS	1372:1451	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	6	17	theme	heptameric	1558:1567	arg1	glycan					1569:1574	the main heptameric glycan	1549:1574	the main heptameric glycan	1549:1574	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	0	18	from	archaellins	49:59	arg1	Identification					0:13	Identification	0:13	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.	0:153	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	4	19	theme	glycan	728:733	arg1	modifications					735:747	the N-linked glycan modifications	715:747	the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	715:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	2	20	gly	N-Glycosylation	235:249	arg1	archaellins					285:295	archaellins	285:295	archaellins	285:295	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	2	20	gly	N-Glycosylation	235:249	arg1	proteins					275:282	the major structural proteins	254:282	the major structural proteins (archaellins)	254:296	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	7	21	theme	N-glycosylation	1693:1707	arg1	pathway					1709:1715	a common N-glycosylation pathway	1684:1715	a common N-glycosylation pathway	1684:1715	In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway.
32817340	3	22	theme	archaeal	629:636	arg1	glycobiology					638:649	archaeal glycobiology	629:649	archaeal glycobiology in general	629:660	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	6	23	theme	distinct	1535:1542	arg1	variants					1510:1517	several, less abundant glycan variants	1480:1517	several, less abundant glycan variants	1480:1517	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	4	24	dep	archaellins	756:766	arg1	the					752:754	the	752:754	the	752:754	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	2	25	theme	major	258:262	arg1	archaellins					285:295	archaellins	285:295	archaellins	285:295	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	2	25	theme	major	258:262	arg1	proteins					275:282	the major structural proteins	254:282	the major structural proteins (archaellins)	254:296	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	0	26	theme	S-layer	65:71	arg1	protein					73:79	S-layer protein	65:79	S-layer protein	65:79	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	7	27	theme	heptameric	1654:1663	arg1	glycan					1665:1670	the same heptameric glycan	1645:1670	the same heptameric glycan	1645:1670	In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway.
32817340	0	28	from	Identification	0:13	arg1	thermolithotrophicus					133:152	Methanothermococcus thermolithotrophicus	113:152	Methanothermococcus thermolithotrophicus	113:152	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	0	28	from	Identification	0:13	arg1	archaellins					49:59	archaellins	49:59	archaellins	49:59	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	0	28	from	Identification	0:13	arg1	protein					73:79	S-layer protein	65:79	S-layer protein	65:79	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	8	29	theme	N-linked	1757:1764	arg1	larger					1776:1781	larger	1776:1781	larger	1776:1781	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	29	theme	N-linked	1757:1764	arg1	glycan					1766:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	1	30	from	Motility	155:162	arg1	archaea					167:173	archaea	167:173	archaea	167:173	Motility in archaea is facilitated by a unique structure termed the archaellum.
32817340	3	31	dep	meaning	495:501	arg1	shed					535:538	shed	535:538	can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general	531:660	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	4	32	theme	archaellins	992:1002	arg1	FlaB1					1005:1009	FlaB1	1005:1009	FlaB1	1005:1009	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	32	theme	archaellins	992:1002	arg1	archaellins					992:1002	the four predicted archaellins	973:1002	the four predicted archaellins	973:1002	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	32	theme	archaellins	992:1002	arg1	two					966:968	two	966:968	two	966:968	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	32	theme	archaellins	992:1002	arg1	FlaB3					1015:1019	FlaB3	1015:1019	FlaB3	1015:1019	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	33	theme	thermolithotrophicus	811:830	arg1	archaellins					756:766	archaellins	756:766	archaellins	756:766	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	33	theme	thermolithotrophicus	811:830	arg1	protein					780:786	S-layer protein	772:786	S-layer protein	772:786	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	0	34	theme	thermophilic	88:99	arg1	methanogen					101:110	the thermophilic methanogen	84:110	the thermophilic methanogen	84:110	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	4	35	from	archaellins	756:766	arg1	characterization					695:710	the structural characterization	680:710	the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	680:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	3	36	theme	some	392:395	arg1	identity					380:387	The identity	376:387	The identity of some of these N-glycans	376:414	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	4	37	theme	S-layer	772:778	arg1	protein					780:786	S-layer protein	772:786	S-layer protein	772:786	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	38	dep	°C.	873:875	arg1	revealed					902:909	revealed	902:909	revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	902:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	0	39	dep	archaellins	49:59	arg1	the					45:47	the	45:47	the	45:47	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	0	40	theme	N-linked	26:33	arg1	glycan					35:40	a novel N-linked glycan	18:40	a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus	18:152	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	8	41	theme	related	1855:1861	arg1	methanogens					1874:1884	related mesophilic methanogens	1855:1884	related mesophilic methanogens	1855:1884	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	4	42	from	modifications	735:747	arg1	archaellins					756:766	archaellins	756:766	archaellins	756:766	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	42	from	modifications	735:747	arg1	protein					780:786	S-layer protein	772:786	S-layer protein	772:786	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	5	43	theme	α-d-glycero-d-manno-Hep3OMe6OMe-	1230:1261	arg1	-[α-GalNAcA3OMe-					1267:1282	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)	1230:1287	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)	1230:1287	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	6	44	theme	liquid	1424:1429	arg1	chromatography-MS					1435:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	5	45	theme	glycan	1192:1197	arg1	analysis					1167:1174	NMR analysis	1163:1174	NMR analysis of the purified glycan	1163:1197	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	6	46	dep	several	1480:1486	arg1	abundant					1494:1501	abundant	1494:1501	abundant	1494:1501	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	3	47	from	glycobiology	638:649	arg1	general					654:660	general	654:660	general	654:660	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	6	48	theme	hydrophilic	1400:1410	arg1	chromatography-MS					1435:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	4	49	theme	N	1135:1135	arg1	termini					1137:1143	the N termini	1131:1143	the N termini of both proteins	1131:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	8	50	theme	mesophilic	1863:1872	arg1	methanogens					1874:1884	related mesophilic methanogens	1855:1884	related mesophilic methanogens	1855:1884	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	4	51	link	N-linked	1083:1090	arg1	sequons					1092:1098	all N-linked sequons	1079:1098	all N-linked sequons except for the site closest to the N termini of both proteins	1079:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	6	52	theme	variants	1510:1517	arg1	presence					1468:1475	the presence	1464:1475	the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan	1464:1574	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	4	53	link	N-linked	719:726	arg1	modifications					735:747	the N-linked glycan modifications	715:747	the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	715:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	3	54	theme	specific	562:569	arg1	details					571:577	the specific details	558:577	the specific details of archaellin structure and function	558:614	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	3	55	theme	archaellin	582:591	arg1	structure					593:601	archaellin structure	582:601	archaellin structure	582:601	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	0	56	from	protein	73:79	arg1	Identification					0:13	Identification	0:13	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.	0:153	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	2	57	theme	archaellum	355:364	arg1	filament					366:373	the archaellum filament	351:373	the archaellum filament	351:373	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	3	58	theme	function	607:614	arg1	details					571:577	the specific details	558:577	the specific details of archaellin structure and function	558:614	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	3	59	theme	structure	593:601	arg1	details					571:577	the specific details	558:577	the specific details of archaellin structure and function	558:614	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	6	60	theme	main	1553:1556	arg1	glycan					1569:1574	the main heptameric glycan	1549:1574	the main heptameric glycan	1549:1574	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	4	61	theme	sheared	920:926	arg1	archaella					928:936	the sheared archaella	916:936	the sheared archaella	916:936	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	62	theme	N-linked	719:726	arg1	modifications					735:747	the N-linked glycan modifications	715:747	the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	715:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	8	63	dep	maripaludis	1926:1936	arg1	indicate					1949:1956	indicate	1949:1956	could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures	1943:2073	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	64	theme	M.	1722:1723	arg1	larger					1776:1781	larger	1776:1781	larger	1776:1781	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	64	theme	M.	1722:1723	arg1	glycan					1766:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	4	65	from	sequons	1092:1098	arg1	glycan					1069:1074	a branched, heptameric glycan	1046:1074	a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	1046:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	66	theme	proteins	1153:1160	arg1	termini					1137:1143	the N termini	1131:1143	the N termini of both proteins	1131:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	67	theme	modifications	735:747	arg1	characterization					695:710	the structural characterization	680:710	the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	680:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	2	68	theme	structural	264:273	arg1	archaellins					285:295	archaellins	285:295	archaellins	285:295	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	2	68	theme	structural	264:273	arg1	proteins					275:282	the major structural proteins	254:282	the major structural proteins (archaellins)	254:296	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	8	69	theme	archaellin	1746:1755	arg1	larger					1776:1781	larger	1776:1781	larger	1776:1781	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	69	theme	archaellin	1746:1755	arg1	glycan					1766:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan	1718:1771	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	7	70	theme	common	1686:1691	arg1	pathway					1709:1715	a common N-glycosylation pathway	1684:1715	a common N-glycosylation pathway	1684:1715	In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway.
32817340	4	71	theme	structural	684:693	arg1	characterization					695:710	the structural characterization	680:710	the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	680:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	2	72	theme	proteins	275:282	arg1	N-Glycosylation					235:249	N-Glycosylation	235:249	N-Glycosylation of the major structural proteins (archaellins)	235:296	N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament.
32817340	6	73	theme	related	1520:1526	arg1	variants					1510:1517	several, less abundant glycan variants	1480:1517	several, less abundant glycan variants	1480:1517	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
32817340	5	74	theme	-[α-GalNAcA3OMe-	1267:1282	arg1	-β-GalNAc-Asn					1357:1369	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn	1230:1369	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn	1230:1369	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	8	75	theme	glycan	1981:1986	arg1	modification					1988:1999	the glycan modification	1977:1999	the glycan modification	1977:1999	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	5	76	theme	-[β-GalA3OMe4OAc6CMe-	1302:1322	arg1	-α-GalA-					1328:1335	]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-	1289:1341	]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-	1289:1341	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	0	77	theme	methanogen	101:110	arg1	thermolithotrophicus					133:152	Methanothermococcus thermolithotrophicus	113:152	Methanothermococcus thermolithotrophicus	113:152	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	0	77	theme	methanogen	101:110	arg1	archaellins					49:59	archaellins	49:59	archaellins	49:59	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	0	77	theme	methanogen	101:110	arg1	protein					73:79	S-layer protein	65:79	S-layer protein	65:79	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	4	78	from	protein	780:786	arg1	characterization					695:710	the structural characterization	680:710	the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	680:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	7	79	theme	same	1649:1652	arg1	glycan					1665:1670	the same heptameric glycan	1645:1670	the same heptameric glycan	1645:1670	In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway.
32817340	8	80	theme	elevated	2053:2060	arg1	temperatures					2062:2073	elevated temperatures	2053:2073	elevated temperatures	2053:2073	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	4	81	theme	predicted	982:990	arg1	archaellins					992:1002	the four predicted archaellins	973:1002	the four predicted archaellins	973:1002	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	0	82	from	glycan	35:40	arg1	thermolithotrophicus					133:152	Methanothermococcus thermolithotrophicus	113:152	Methanothermococcus thermolithotrophicus	113:152	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	0	82	from	glycan	35:40	arg1	archaellins					49:59	archaellins	49:59	archaellins	49:59	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	0	82	from	glycan	35:40	arg1	protein					73:79	S-layer protein	65:79	S-layer protein	65:79	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	3	83	theme	extensive	457:465	arg1	variation					467:475	extensive variation	457:475	extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general	457:660	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	5	84	theme	-β-Man-	1290:1296	arg1	-α-GalA-					1328:1335	]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-	1289:1341	]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-	1289:1341	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	0	85	theme	novel	20:24	arg1	glycan					35:40	a novel N-linked glycan	18:40	a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus	18:152	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	4	86	mod	modified	1032:1039	arg1	archaellins					992:1002	the four predicted archaellins	973:1002	the four predicted archaellins	973:1002	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	86	mod	modified	1032:1039	arg1	FlaB1					1005:1009	FlaB1	1005:1009	FlaB1	1005:1009	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	86	mod	modified	1032:1039	arg3	glycan					1069:1074	a branched, heptameric glycan	1046:1074	a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	1046:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	86	mod	modified	1032:1039	arg1	two					966:968	two	966:968	two	966:968	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	86	mod	modified	1032:1039	arg1	FlaB3					1015:1019	FlaB3	1015:1019	FlaB3	1015:1019	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	4	87	theme	branched	1048:1055	arg1	glycan					1069:1074	a branched, heptameric glycan	1046:1074	a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins	1046:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	0	88	theme	glycan	35:40	arg1	Identification					0:13	Identification	0:13	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.	0:153	Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.
32817340	5	89	theme	purified	1183:1190	arg1	glycan					1192:1197	the purified glycan	1179:1197	the purified glycan	1179:1197	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	7	90	theme	S-layer	1612:1618	arg1	protein					1620:1626	the S-layer protein	1608:1626	the S-layer protein	1608:1626	In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway.
32817340	3	91	from	variation	467:475	arg1	meaning					495:501	meaning	495:501	meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general	495:660	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	3	91	from	variation	467:475	arg1	glycans					486:492	their glycans	480:492	their glycans	480:492	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	8	92	theme	modification	1988:1999	arg1	nature					1967:1972	the nature	1963:1972	the nature of the glycan modification	1963:1999	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	5	93	theme	-α-GalAN-	1343:1351	arg1	-β-GalNAc-Asn					1357:1369	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn	1230:1369	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn	1230:1369	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	3	94	theme	further	508:514	arg1	investigations					516:529	further investigations	508:529	further investigations	508:529	The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general.
32817340	5	95	theme	NMR	1163:1165	arg1	analysis					1167:1174	NMR analysis	1163:1174	NMR analysis of the purified glycan	1163:1197	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	4	96	theme	N-linked	1083:1090	arg1	sequons					1092:1098	all N-linked sequons	1079:1098	all N-linked sequons except for the site closest to the N termini of both proteins	1079:1160	Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins.
32817340	5	97	theme	-α-GalA-	1328:1335	arg1	-β-GalNAc-Asn					1357:1369	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn	1230:1369	α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn	1230:1369	NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-β-Man-(1-4)-[β-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-β-GalNAc-Asn.
32817340	8	98	contain	have	2005:2008	arg1	nature					1967:1972	the nature	1963:1972	the nature of the glycan modification	1963:1999	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	8	98	contain	have	2005:2008	arg2	role					2012:2015	a role to play in maintaining stability at elevated temperatures	2010:2073	a role to play in maintaining stability at elevated temperatures	2010:2073	The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.
32817340	6	99	theme	ion	1431:1433	arg1	chromatography-MS					1435:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	hydrophilic interaction liquid ion chromatography-MS	1400:1451	A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan.
33664400	5	0	theme	binding	763:769	arg1	site					771:774	an entirely different micromolar binding site	730:774	an entirely different micromolar binding site	730:774	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	6	1	theme	host	899:902	arg1	protein					904:910	the host protein	895:910	the host protein	895:910	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	6	2	theme	first	804:808	arg1	time					810:813	the first time	800:813	the first time	800:813	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	1	3	theme	information	167:177	arg1	layer					158:162	a complementary layer	142:162	a complementary layer of information to protein function	142:197	While DNA encodes protein structure, glycans provide a complementary layer of information to protein function.
33664400	2	4	theme	surface	275:281	arg1	CD44					292:295	the cell surface receptor CD44	266:295	the cell surface receptor CD44	266:295	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	5	5	theme	canonical	645:653	arg1	site					678:681	the canonical sub-micromolar binding site	641:681	the canonical sub-micromolar binding site	641:681	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	2	6	theme	cell	270:273	arg1	CD44					292:295	the cell surface receptor CD44	266:295	the cell surface receptor CD44	266:295	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	6	7	theme	specific	875:882	arg1	regions					884:890	specific regions	875:890	specific regions of the host protein	875:910	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	7	8	theme	protein	1078:1084	arg1	determination					1096:1108	protein structure determination	1078:1108	protein structure determination where glycosylation is usually neglected	1078:1149	The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
33664400	4	9	contain	has	488:490	arg2	sites					518:522	multiple distinct binding sites	492:522	multiple distinct binding sites for hyaluronan	492:537	Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles.
33664400	4	9	contain	has	488:490	arg1	CD44					483:486	CD44	483:486	CD44	483:486	Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles.
33664400	7	10	theme	structure	1086:1094	arg1	determination					1096:1108	protein structure determination	1078:1108	protein structure determination where glycosylation is usually neglected	1078:1149	The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
33664400	6	11	dep	show	790:793	arg1	time					810:813	the first time	800:813	the first time	800:813	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	1	12	theme	protein	182:188	arg1	function					190:197	protein function	182:197	protein function	182:197	While DNA encodes protein structure, glycans provide a complementary layer of information to protein function.
33664400	7	13	theme	protein	1035:1041	arg1	function					1043:1050	protein function	1035:1050	protein function	1035:1050	The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
33664400	3	14	theme	modulation	391:400	arg1	details					375:381	the details	371:381	the details of this modulation	371:400	However, the details of this modulation remain unclear.
33664400	5	15	theme	non-glycosylated	612:627	arg1	CD44					629:632	non-glycosylated CD44	612:632	non-glycosylated CD44	612:632	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	2	16	theme	CD44	292:295	arg1	example					211:217	a prime example	203:217	a prime example of the significance of glycans	203:248	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	2	16	theme	CD44	292:295	arg1	ability					255:261	the ability	251:261	the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan,	251:327	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	5	17	theme	glycosylated	690:701	arg1	CD44					703:706	glycosylated CD44	690:706	glycosylated CD44	690:706	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	2	18	theme	receptor	283:290	arg1	CD44					292:295	the cell surface receptor CD44	266:295	the cell surface receptor CD44	266:295	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	6	19	theme	binding	938:944	arg1	modes					946:950	weaker binding modes	931:950	weaker binding modes	931:950	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	6	20	theme	receptor	844:851	arg1	affinity					853:860	receptor affinity	844:860	receptor affinity	844:860	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	5	21	gly	non-glycosylated	612:627	arg1	CD44					629:632	non-glycosylated CD44	612:632	non-glycosylated CD44	612:632	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	4	22	theme	multiple	492:499	arg1	sites					518:522	multiple distinct binding sites	492:522	multiple distinct binding sites for hyaluronan	492:537	Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles.
33664400	2	23	theme	significance	226:237	arg1	ability					255:261	the ability	251:261	the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan,	251:327	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	2	23	theme	significance	226:237	arg1	example					211:217	a prime example	203:217	a prime example of the significance of glycans	203:248	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	7	24	from	importance	1004:1013	arg1	function					1043:1050	protein function	1035:1050	protein function	1035:1050	The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
33664400	0	25	theme	receptor-ligand	58:72	arg1	modes					82:86	different receptor-ligand binding modes	48:86	different receptor-ligand binding modes	48:86	N-Glycosylation can selectively block or foster different receptor-ligand binding modes.
33664400	6	26	theme	weaker	931:936	arg1	modes					946:950	weaker binding modes	931:950	weaker binding modes	931:950	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	5	27	theme	sub-micromolar	655:668	arg1	site					678:681	the canonical sub-micromolar binding site	641:681	the canonical sub-micromolar binding site	641:681	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	4	28	theme	atomistic	427:435	arg1	simulations					437:447	atomistic simulations	427:447	atomistic simulations	427:447	Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles.
33664400	5	29	gly	glycosylated	690:701	arg1	CD44					703:706	glycosylated CD44	690:706	glycosylated CD44	690:706	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	0	30	theme	different	48:56	arg1	modes					82:86	different receptor-ligand binding modes	48:86	different receptor-ligand binding modes	48:86	N-Glycosylation can selectively block or foster different receptor-ligand binding modes.
33664400	4	31	theme	binding	510:516	arg1	sites					518:522	multiple distinct binding sites	492:522	multiple distinct binding sites for hyaluronan	492:537	Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles.
33664400	5	32	theme	binding	670:676	arg1	site					678:681	the canonical sub-micromolar binding site	641:681	the canonical sub-micromolar binding site	641:681	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	4	33	theme	distinct	501:508	arg1	sites					518:522	multiple distinct binding sites	492:522	multiple distinct binding sites for hyaluronan	492:537	Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles.
33664400	2	34	theme	prime	205:209	arg1	ability					255:261	the ability	251:261	the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan,	251:327	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	2	34	theme	prime	205:209	arg1	example					211:217	a prime example	203:217	a prime example of the significance of glycans	203:248	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
33664400	5	35	theme	micromolar	752:761	arg1	site					771:774	an entirely different micromolar binding site	730:774	an entirely different micromolar binding site	730:774	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	1	36	theme	protein	107:113	arg1	DNA					95:97	DNA	95:97	DNA	95:97	While DNA encodes protein structure, glycans provide a complementary layer of information to protein function.
33664400	1	36	theme	protein	107:113	arg1	structure					115:123	protein structure	107:123	protein structure	107:123	While DNA encodes protein structure, glycans provide a complementary layer of information to protein function.
33664400	4	37	theme	respective	581:590	arg1	roles					592:596	their respective roles	575:596	their respective roles	575:596	Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles.
33664400	7	38	theme	glycosylation	1018:1030	arg1	importance					1004:1013	the importance	1000:1013	the importance of glycosylation in protein function	1000:1050	The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
33664400	5	39	theme	different	742:750	arg1	site					771:774	an entirely different micromolar binding site	730:774	an entirely different micromolar binding site	730:774	We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site.
33664400	1	40	theme	complementary	144:156	arg1	layer					158:162	a complementary layer	142:162	a complementary layer of information to protein function	142:197	While DNA encodes protein structure, glycans provide a complementary layer of information to protein function.
33664400	0	41	theme	binding	74:80	arg1	modes					82:86	different receptor-ligand binding modes	48:86	different receptor-ligand binding modes	48:86	N-Glycosylation can selectively block or foster different receptor-ligand binding modes.
33664400	6	42	theme	protein	904:910	arg1	regions					884:890	specific regions	875:890	specific regions of the host protein	875:910	Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes.
33664400	2	43	theme	glycans	242:248	arg1	significance					226:237	the significance	222:237	the significance of glycans	222:248	As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation.
34106099	2	0	from	proteins	190:197	arg1	brain					206:210	the brain	202:210	the brain associated with the synapse and important for synaptic transmission	202:278	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	6	1	theme	zone	950:953	arg1	proteins					955:962	the active zone proteins	939:962	the active zone proteins from the synaptosomes	939:984	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	9	2	theme	fragmentation	1707:1719	arg1	lack					1682:1685	the lack	1678:1685	the lack of peptide backbone fragmentation during tandem mass spectrometry	1678:1751	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	9	3	gly	sialylated	1592:1601	arg1	glycopeptides					1612:1624	intact sialylated N-linked glycopeptides	1585:1624	intact sialylated N-linked glycopeptides using the Byonic program	1585:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	7	4	theme	titanium	1176:1183	arg1	dioxide					1185:1191	titanium dioxide	1176:1191	titanium dioxide chromatography	1176:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	3	5	theme	glycan-	526:532	arg1	analyses					566:573	glycan- and intact glycopeptide-focused analyses	526:573	glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes)	526:620	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	9	6	theme	tandem	1728:1733	arg1	spectrometry					1740:1751	tandem mass spectrometry	1728:1751	tandem mass spectrometry	1728:1751	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	3	7	theme	isolated	578:585	arg1	synaptosomes					608:619	synaptosomes	608:619	synaptosomes	608:619	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	3	7	theme	isolated	578:585	arg1	terminals					597:605	isolated rat nerve terminals	578:605	isolated rat nerve terminals (synaptosomes)	578:620	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	5	8	with	N-glycome	802:810	arg1	oligomannose					817:828	oligomannose	817:828	oligomannose	817:828	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	4	9	theme	N-glycans	679:687	arg1	total					667:671	a total	665:671	a total of 41 N-glycans in isolated synaptosomes	665:712	Overall, glycomics identified a total of 41 N-glycans in isolated synaptosomes.
34106099	6	10	from	extraction	925:934	arg1	synaptosomes					973:984	the synaptosomes	969:984	the synaptosomes	969:984	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	7	11	theme	N-linked	1141:1148	arg1	glycopeptides					1150:1162	intact sialylated N-linked glycopeptides	1123:1162	intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography	1123:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	8	12	gly	glycoproteins	1501:1513	arg1	glycoproteins					1501:1513	glycoproteins	1501:1513	glycoproteins	1501:1513	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	4	13	theme	isolated	692:699	arg1	synaptosomes					701:712	isolated synaptosomes	692:712	isolated synaptosomes	692:712	Overall, glycomics identified a total of 41 N-glycans in isolated synaptosomes.
34106099	1	14	link	N-linked	49:56	arg1	modification					96:107	a ubiquitous protein modification	75:107	a ubiquitous protein modification that is capable of modulating protein structure, function and interactions	75:182	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	14	link	N-linked	49:56	arg1	glycosylation					58:70	N-linked glycosylation	49:70	N-linked glycosylation	49:70	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	14	link	N-linked	49:56	arg1	capable					117:123	capable	117:123	capable	117:123	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	7	15	theme	intact	1123:1128	arg1	glycopeptides					1150:1162	intact sialylated N-linked glycopeptides	1123:1162	intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography	1123:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	8	16	from	present	1490:1496	arg1	fraction					1540:1547	the detergent soluble fraction	1518:1547	the detergent soluble fraction	1518:1547	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	3	17	theme	nerve	591:595	arg1	synaptosomes					608:619	synaptosomes	608:619	synaptosomes	608:619	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	3	17	theme	nerve	591:595	arg1	terminals					597:605	isolated rat nerve terminals	578:605	isolated rat nerve terminals (synaptosomes)	578:620	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	6	18	with	comparison	1043:1052	arg1	rest					1063:1066	the rest	1059:1066	the rest of the synaptosome glycan content	1059:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	8	19	theme	disialic	1334:1341	arg1	glycans					1371:1377	both disialic and trisialic acid modified glycans	1329:1377	both disialic and trisialic acid modified glycans	1329:1377	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	7	20	from	presence	1273:1280	arg1	proteins					1306:1313	active zone proteins	1294:1313	active zone proteins	1294:1313	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	8	21	theme	detergent	1522:1530	arg1	fraction					1540:1547	the detergent soluble fraction	1518:1547	the detergent soluble fraction	1518:1547	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	22	theme	trisialic	1347:1355	arg1	glycans					1371:1377	both disialic and trisialic acid modified glycans	1329:1377	both disialic and trisialic acid modified glycans	1329:1377	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	2	23	theme	synaptic	258:265	arg1	transmission					267:278	synaptic transmission	258:278	synaptic transmission	258:278	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	1	24	theme	protein	139:145	arg1	structure					147:155	protein structure	139:155	protein structure	139:155	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	8	25	theme	modified	1362:1369	arg1	glycans					1371:1377	both disialic and trisialic acid modified glycans	1329:1377	both disialic and trisialic acid modified glycans	1329:1377	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	7	26	theme	NeuGc	1285:1289	arg1	presence					1273:1280	the presence	1269:1280	the presence of NeuGc on active zone proteins	1269:1313	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	7	26	theme	NeuGc	1285:1289	arg1	selectivity					1231:1241	more than 85% selectivity	1217:1241	more than 85% selectivity of sialylated species	1217:1263	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	5	27	theme	complex	850:856	arg1	hybrid					839:844	neutral hybrid and complex type N-glycans	831:871	hybrid	839:844	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	27	theme	complex	850:856	arg1	structures					897:906	the most abundant structures	879:906	the most abundant structures	879:906	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	27	theme	complex	850:856	arg1	N-glycans					863:871	neutral hybrid and complex type N-glycans	831:871	N-glycans	863:871	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	9	28	theme	intact	1585:1590	arg1	glycopeptides					1612:1624	intact sialylated N-linked glycopeptides	1585:1624	intact sialylated N-linked glycopeptides using the Byonic program	1585:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	5	29	theme	synaptosome	790:800	arg1	abundance					769:777	the total abundance	759:777	the total abundance of the rat synaptosome N-glycome with oligomannose	759:828	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	9	30	theme	N-linked	1603:1610	arg1	glycopeptides					1612:1624	intact sialylated N-linked glycopeptides	1585:1624	intact sialylated N-linked glycopeptides using the Byonic program	1585:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	6	31	theme	glycan	1023:1028	arg1	abundance					1030:1038	the active zone glycan abundance	1007:1038	the active zone glycan abundance in comparison with the rest of the synaptosome glycan content	1007:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	0	32	from	N-Glycosylation	0:14	arg1	terminals					38:46	isolated rat nerve terminals	19:46	isolated rat nerve terminals	19:46	N-Glycosylation in isolated rat nerve terminals.
34106099	7	33	dep	%	1229:1229	arg1	85					1227:1228	85	1227:1228	85	1227:1228	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	2	34	dep	learning	351:358	arg1	processes					389:397	related molecular processes	371:397	related molecular processes	371:397	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	8	35	from	fraction	1540:1547	arg1	present					1490:1496	present	1490:1496	present	1490:1496	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	6	36	theme	active	1011:1016	arg1	abundance					1030:1038	the active zone glycan abundance	1007:1038	the active zone glycan abundance in comparison with the rest of the synaptosome glycan content	1007:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	7	37	gly	sialylated	1246:1255	arg1	species					1257:1263	sialylated species	1246:1263	sialylated species	1246:1263	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	5	38	theme	abundance	769:777	arg1	abundance					769:777	the total abundance	759:777	the total abundance of the rat synaptosome N-glycome with oligomannose	759:828	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	38	theme	abundance	769:777	arg1	%					754:754	only 7%	748:754	only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose	748:828	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	1	39	theme	ubiquitous	77:86	arg1	modification					96:107	a ubiquitous protein modification	75:107	a ubiquitous protein modification that is capable of modulating protein structure, function and interactions	75:182	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	39	theme	ubiquitous	77:86	arg1	glycosylation					58:70	N-linked glycosylation	49:70	N-linked glycosylation	49:70	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	39	theme	ubiquitous	77:86	arg1	capable					117:123	capable	117:123	capable	117:123	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	7	40	from	selectivity	1231:1241	arg1	proteins					1306:1313	active zone proteins	1294:1313	active zone proteins	1294:1313	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	6	41	from	abundance	1030:1038	arg1	comparison					1043:1052	comparison	1043:1052	comparison with the rest of the synaptosome glycan content	1043:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	2	42	theme	synaptic	403:410	arg1	plasticity					412:421	synaptic plasticity	403:421	synaptic plasticity	403:421	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	6	43	theme	glycan	1087:1092	arg1	content					1094:1100	the synaptosome glycan content	1071:1100	the synaptosome glycan content	1071:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	9	44	gly	glycopeptides	1612:1624	arg2	glycopeptides					1612:1624	intact sialylated N-linked glycopeptides	1585:1624	intact sialylated N-linked glycopeptides using the Byonic program	1585:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	6	45	from	change	997:1002	arg1	abundance					1030:1038	the active zone glycan abundance	1007:1038	the active zone glycan abundance in comparison with the rest of the synaptosome glycan content	1007:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	8	46	theme	ion	1436:1438	arg1	profiling					1440:1448	oxonium ion profiling	1428:1448	oxonium ion profiling	1428:1448	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	0	47	theme	isolated	19:26	arg1	terminals					38:46	isolated rat nerve terminals	19:46	isolated rat nerve terminals	19:46	N-Glycosylation in isolated rat nerve terminals.
34106099	9	48	link	N-linked	1603:1610	arg1	glycopeptides					1612:1624	intact sialylated N-linked glycopeptides	1585:1624	intact sialylated N-linked glycopeptides using the Byonic program	1585:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	3	49	theme	present	431:437	arg1	study					439:443	the present study	427:443	the present study	427:443	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	2	50	theme	Many	185:188	arg1	proteins					190:197	Many proteins	185:197	Many proteins in the brain associated with the synapse and important for synaptic transmission	185:278	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	0	51	theme	nerve	32:36	arg1	terminals					38:46	isolated rat nerve terminals	19:46	isolated rat nerve terminals	19:46	N-Glycosylation in isolated rat nerve terminals.
34106099	8	52	theme	trisialic	1464:1472	arg1	units					1474:1478	trisialic units	1464:1478	trisialic units	1464:1478	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	3	53	theme	glycoproteome	498:510	arg1	knowledge					460:468	the knowledge	456:468	the knowledge of the synaptic glycome and glycoproteome	456:510	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	8	54	attach	present	1490:1496	arg1	fraction					1540:1547	the detergent soluble fraction	1518:1547	the detergent soluble fraction	1518:1547	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	54	attach	present	1490:1496	arg2	units					1474:1478	trisialic units	1464:1478	trisialic units	1464:1478	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	54	attach	present	1490:1496	arg1	glycoproteins					1501:1513	glycoproteins	1501:1513	glycoproteins	1501:1513	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	3	55	theme	glycome	486:492	arg1	knowledge					460:468	the knowledge	456:468	the knowledge of the synaptic glycome and glycoproteome	456:510	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	5	56	theme	abundant	888:895	arg1	hybrid					839:844	neutral hybrid and complex type N-glycans	831:871	hybrid	839:844	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	56	theme	abundant	888:895	arg1	structures					897:906	the most abundant structures	879:906	the most abundant structures	879:906	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	56	theme	abundant	888:895	arg1	N-glycans					863:871	neutral hybrid and complex type N-glycans	831:871	N-glycans	863:871	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	6	57	theme	proteins	955:962	arg1	extraction					925:934	detergent extraction	915:934	detergent extraction of the active zone proteins from the synaptosomes	915:984	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	1	58	theme	N-linked	49:56	arg1	modification					96:107	a ubiquitous protein modification	75:107	a ubiquitous protein modification that is capable of modulating protein structure, function and interactions	75:182	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	58	theme	N-linked	49:56	arg1	glycosylation					58:70	N-linked glycosylation	49:70	N-linked glycosylation	49:70	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	58	theme	N-linked	49:56	arg1	capable					117:123	capable	117:123	capable	117:123	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	2	59	dep	brain	206:210	arg1	important					244:252	important	244:252	important	244:252	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	2	59	dep	brain	206:210	arg1	associated					212:221	associated	212:221	associated with the synapse	212:238	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	2	60	theme	related	371:377	arg1	processes					389:397	related molecular processes	371:397	related molecular processes	371:397	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	6	61	theme	active	943:948	arg1	proteins					955:962	the active zone proteins	939:962	the active zone proteins from the synaptosomes	939:984	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	7	62	theme	active	1294:1299	arg1	proteins					1306:1313	active zone proteins	1294:1313	active zone proteins	1294:1313	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	2	63	gly	glycosylated	291:302	arg1	proteins					190:197	Many proteins	185:197	Many proteins in the brain associated with the synapse and important for synaptic transmission	185:278	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	7	64	theme	glycopeptides	1150:1162	arg1	Characterization					1103:1118	Characterization	1103:1118	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography	1103:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	9	65	theme	mass	1735:1738	arg1	spectrometry					1740:1751	tandem mass spectrometry	1728:1751	tandem mass spectrometry	1728:1751	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	7	66	theme	sialylated	1130:1139	arg1	glycopeptides					1150:1162	intact sialylated N-linked glycopeptides	1123:1162	intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography	1123:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	3	67	theme	glycopeptide-focused	545:564	arg1	analyses					566:573	glycan- and intact glycopeptide-focused analyses	526:573	glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes)	526:620	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	6	68	theme	detergent	915:923	arg1	extraction					925:934	detergent extraction	915:934	detergent extraction of the active zone proteins from the synaptosomes	915:984	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	7	69	gly	sialylated	1130:1139	arg1	glycopeptides					1150:1162	intact sialylated N-linked glycopeptides	1123:1162	intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography	1123:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	3	70	theme	terminals	597:605	arg1	analyses					566:573	glycan- and intact glycopeptide-focused analyses	526:573	glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes)	526:620	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	3	71	theme	rat	587:589	arg1	synaptosomes					608:619	synaptosomes	608:619	synaptosomes	608:619	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	3	71	theme	rat	587:589	arg1	terminals					597:605	isolated rat nerve terminals	578:605	isolated rat nerve terminals (synaptosomes)	578:620	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	4	72	from	total	667:671	arg1	synaptosomes					701:712	isolated synaptosomes	692:712	isolated synaptosomes	692:712	Overall, glycomics identified a total of 41 N-glycans in isolated synaptosomes.
34106099	5	73	theme	type	858:861	arg1	hybrid					839:844	neutral hybrid and complex type N-glycans	831:871	hybrid	839:844	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	73	theme	type	858:861	arg1	structures					897:906	the most abundant structures	879:906	the most abundant structures	879:906	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	73	theme	type	858:861	arg1	N-glycans					863:871	neutral hybrid and complex type N-glycans	831:871	N-glycans	863:871	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	7	74	gly	glycopeptides	1150:1162	arg2	glycopeptides					1150:1162	intact sialylated N-linked glycopeptides	1123:1162	intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography	1123:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	8	75	located	present	1490:1496	arg1	fraction					1540:1547	the detergent soluble fraction	1518:1547	the detergent soluble fraction	1518:1547	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	75	located	present	1490:1496	arg2	units					1474:1478	trisialic units	1464:1478	trisialic units	1464:1478	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	75	located	present	1490:1496	arg1	glycoproteins					1501:1513	glycoproteins	1501:1513	glycoproteins	1501:1513	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	76	theme	soluble	1532:1538	arg1	fraction					1540:1547	the detergent soluble fraction	1518:1547	the detergent soluble fraction	1518:1547	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	5	77	theme	Sialylated	715:724	arg1	N-glycans					726:734	Sialylated N-glycans	715:734	Sialylated N-glycans	715:734	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	9	78	theme	correct	1559:1565	arg1	identification					1567:1580	correct identification	1559:1580	correct identification of intact sialylated N-linked glycopeptides using the Byonic program	1559:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	8	79	attach	present	1384:1390	arg2	glycans					1371:1377	both disialic and trisialic acid modified glycans	1329:1377	both disialic and trisialic acid modified glycans	1329:1377	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	79	attach	present	1384:1390	arg1	addition					1319:1326	addition	1319:1326	addition	1319:1326	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	79	attach	present	1384:1390	arg1	glycoproteins					1404:1416	synaptic glycoproteins	1395:1416	synaptic glycoproteins	1395:1416	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	80	from	addition	1319:1326	arg1	present					1384:1390	present	1384:1390	present	1384:1390	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	7	81	attach	presence	1273:1280	arg2	NeuGc					1285:1289	NeuGc	1285:1289	NeuGc	1285:1289	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	7	81	attach	presence	1273:1280	arg1	proteins					1306:1313	active zone proteins	1294:1313	active zone proteins	1294:1313	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	7	81	attach	presence	1273:1280	arg2	species					1257:1263	sialylated species	1246:1263	sialylated species	1246:1263	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	8	82	theme	acid	1357:1360	arg1	glycans					1371:1377	both disialic and trisialic acid modified glycans	1329:1377	both disialic and trisialic acid modified glycans	1329:1377	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	5	83	theme	rat	786:788	arg1	synaptosome					790:800	the rat synaptosome	782:800	the rat synaptosome N-glycome with oligomannose	782:828	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	9	84	theme	sialylated	1592:1601	arg1	glycopeptides					1612:1624	intact sialylated N-linked glycopeptides	1585:1624	intact sialylated N-linked glycopeptides using the Byonic program	1585:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	7	85	theme	species	1257:1263	arg1	presence					1273:1280	the presence	1269:1280	the presence of NeuGc on active zone proteins	1269:1313	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	7	85	theme	species	1257:1263	arg1	selectivity					1231:1241	more than 85% selectivity	1217:1241	more than 85% selectivity of sialylated species	1217:1263	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	9	86	theme	glycopeptides	1612:1624	arg1	identification					1567:1580	correct identification	1559:1580	correct identification of intact sialylated N-linked glycopeptides using the Byonic program	1559:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	6	87	theme	zone	1018:1021	arg1	abundance					1030:1038	the active zone glycan abundance	1007:1038	the active zone glycan abundance in comparison with the rest of the synaptosome glycan content	1007:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	7	88	dep	selectivity	1231:1241	arg1	%					1229:1229	%	1229:1229	%	1229:1229	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	5	89	theme	total	763:767	arg1	abundance					769:777	the total abundance	759:777	the total abundance of the rat synaptosome N-glycome with oligomannose	759:828	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	8	90	theme	synaptic	1395:1402	arg1	glycoproteins					1404:1416	synaptic glycoproteins	1395:1416	synaptic glycoproteins	1395:1416	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	5	91	theme	neutral	831:837	arg1	hybrid					839:844	neutral hybrid and complex type N-glycans	831:871	hybrid	839:844	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	91	theme	neutral	831:837	arg1	structures					897:906	the most abundant structures	879:906	the most abundant structures	879:906	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	5	91	theme	neutral	831:837	arg1	N-glycans					863:871	neutral hybrid and complex type N-glycans	831:871	N-glycans	863:871	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	9	92	theme	Byonic	1636:1641	arg1	program					1643:1649	the Byonic program	1632:1649	the Byonic program	1632:1649	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	1	93	theme	protein	88:94	arg1	modification					96:107	a ubiquitous protein modification	75:107	a ubiquitous protein modification that is capable of modulating protein structure, function and interactions	75:182	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	93	theme	protein	88:94	arg1	glycosylation					58:70	N-linked glycosylation	49:70	N-linked glycosylation	49:70	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	1	93	theme	protein	88:94	arg1	capable					117:123	capable	117:123	capable	117:123	N-linked glycosylation is a ubiquitous protein modification that is capable of modulating protein structure, function and interactions.
34106099	6	94	theme	content	1094:1100	arg1	rest					1063:1066	the rest	1059:1066	the rest of the synaptosome glycan content	1059:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	7	95	link	N-linked	1141:1148	arg1	glycopeptides					1150:1162	intact sialylated N-linked glycopeptides	1123:1162	intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography	1123:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	0	96	theme	rat	28:30	arg1	terminals					38:46	isolated rat nerve terminals	19:46	isolated rat nerve terminals	19:46	N-Glycosylation in isolated rat nerve terminals.
34106099	6	97	theme	synaptosome	1075:1085	arg1	content					1094:1100	the synaptosome glycan content	1071:1100	the synaptosome glycan content	1071:1100	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	8	98	theme	oxonium	1428:1434	arg1	profiling					1440:1448	oxonium ion profiling	1428:1448	oxonium ion profiling	1428:1448	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	3	99	theme	synaptic	477:484	arg1	glycome					486:492	the synaptic glycome	473:492	the synaptic glycome	473:492	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
34106099	5	100	theme	N-glycome	802:810	arg1	synaptosome					790:800	the rat synaptosome	782:800	the rat synaptosome N-glycome with oligomannose	782:828	Sialylated N-glycans represented only 7% of the total abundance of the rat synaptosome N-glycome with oligomannose, neutral hybrid and complex type N-glycans being the most abundant structures.
34106099	8	101	gly	glycoproteins	1404:1416	arg1	glycoproteins					1404:1416	synaptic glycoproteins	1395:1416	synaptic glycoproteins	1395:1416	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	102	from	present	1384:1390	arg1	addition					1319:1326	addition	1319:1326	addition	1319:1326	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	7	103	theme	sialylated	1246:1255	arg1	species					1257:1263	sialylated species	1246:1263	sialylated species	1246:1263	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	7	104	theme	dioxide	1185:1191	arg1	chromatography					1193:1206	titanium dioxide chromatography	1176:1206	titanium dioxide chromatography	1176:1206	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	9	105	theme	backbone	1698:1705	arg1	fragmentation					1707:1719	peptide backbone fragmentation	1690:1719	peptide backbone fragmentation during tandem mass spectrometry	1690:1751	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	6	106	from	synaptosomes	973:984	arg1	extraction					925:934	detergent extraction	915:934	detergent extraction of the active zone proteins from the synaptosomes	915:984	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	6	106	from	synaptosomes	973:984	arg1	proteins					955:962	the active zone proteins	939:962	the active zone proteins from the synaptosomes	939:984	Using detergent extraction of the active zone proteins from the synaptosomes revealed a change in the active zone glycan abundance in comparison with the rest of the synaptosome glycan content.
34106099	2	107	theme	molecular	379:387	arg1	processes					389:397	related molecular processes	371:397	related molecular processes	371:397	Many proteins in the brain associated with the synapse and important for synaptic transmission are highly glycosylated and their glycosylation could be important for learning and memory related molecular processes and synaptic plasticity.
34106099	8	108	located	present	1384:1390	arg2	glycans					1371:1377	both disialic and trisialic acid modified glycans	1329:1377	both disialic and trisialic acid modified glycans	1329:1377	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	108	located	present	1384:1390	arg1	addition					1319:1326	addition	1319:1326	addition	1319:1326	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	8	108	located	present	1384:1390	arg1	glycoproteins					1404:1416	synaptic glycoproteins	1395:1416	synaptic glycoproteins	1395:1416	In addition, both disialic and trisialic acid modified glycans were present on synaptic glycoproteins, although oxonium ion profiling revealed that trisialic units were only present on glycoproteins in the detergent soluble fraction.
34106099	9	109	theme	peptide	1690:1696	arg1	fragmentation					1707:1719	peptide backbone fragmentation	1690:1719	peptide backbone fragmentation during tandem mass spectrometry	1690:1751	However, correct identification of intact sialylated N-linked glycopeptides using the Byonic program failed, most likely due to the lack of peptide backbone fragmentation during tandem mass spectrometry.
34106099	7	110	theme	zone	1301:1304	arg1	proteins					1306:1313	active zone proteins	1294:1313	active zone proteins	1294:1313	Characterization of intact sialylated N-linked glycopeptides enriched by titanium dioxide chromatography revealed more than 85% selectivity of sialylated species and the presence of NeuGc on active zone proteins.
34106099	3	111	theme	intact	538:543	arg1	analyses					566:573	glycan- and intact glycopeptide-focused analyses	526:573	glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes)	526:620	In the present study, we extend the knowledge of the synaptic glycome and glycoproteome by performing glycan- and intact glycopeptide-focused analyses of isolated rat nerve terminals (synaptosomes) by LC-MS/MS.
30069741	6	0	theme	native	1281:1286	arg1	glycans					1308:1314	native mammalian and plant glycans	1281:1314	native mammalian and plant glycans	1281:1314	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	3	1	with	proteins	531:538	arg1	structures					585:594	authentic or at least compatible glycan structures	545:594	authentic or at least compatible glycan structures	545:594	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	2	2	theme	biological	364:373	arg1	function					375:382	biological function	364:382	biological function	364:382	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	6	3	with	structures	1267:1276	arg1	symbols					1321:1327	symbols	1321:1327	symbols indicating sugar residues	1321:1353	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	5	4	theme	glycans	923:929	arg1	removal					906:912	the removal	902:912	the removal of plant glycans	902:929	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	5	4	theme	glycans	923:929	arg1	replacement					941:951	their replacement	935:951	their replacement with human counterparts	935:975	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	5	5	theme	therapeutic	1138:1148	arg1	proteins					1150:1157	therapeutic proteins	1138:1157	therapeutic proteins	1138:1157	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	6	6	theme	glycans	1308:1314	arg1	structures					1267:1276	Graphical Abstract Typical structures	1240:1276	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues	1240:1353	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	1	7	theme	glycan	160:165	arg1	structures					167:176	the glycan structures	156:176	the glycan structures	156:176	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	1	8	from	proteins	67:74	arg1	eukaryotes					79:88	eukaryotes	79:88	eukaryotes	79:88	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	5	9	theme	antibody	1211:1218	arg1	functions					1229:1237	antibody effector functions	1211:1237	antibody effector functions	1211:1237	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	6	10	theme	short	1375:1379	arg1	form					1381:1384	their short form	1369:1384	their short form	1369:1384	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	6	11	theme	plant	1302:1306	arg1	glycans					1308:1314	native mammalian and plant glycans	1281:1314	native mammalian and plant glycans	1281:1314	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	3	12	theme	authentic	545:553	arg1	structures					585:594	authentic or at least compatible glycan structures	545:594	authentic or at least compatible glycan structures	545:594	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	3	13	theme	compatible	567:576	arg1	structures					585:594	authentic or at least compatible glycan structures	545:594	authentic or at least compatible glycan structures	545:594	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	4	14	theme	glycans	630:636	arg1	replication					609:619	The precise replication	597:619	The precise replication of human glycans	597:636	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	1	15	gly	glycosylated	94:105	arg1	proteins					67:74	Most secreted proteins	53:74	Most secreted proteins in eukaryotes	53:88	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	5	16	theme	vaccines	1091:1098	arg1	immunogenicity					1068:1081	the immunogenicity	1064:1081	the immunogenicity of some vaccines	1064:1098	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	6	17	dep	single-letter	1390:1402	arg1	codes					1404:1408	codes	1404:1408	codes	1404:1408	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	3	18	theme	glycan	578:583	arg1	structures					585:594	authentic or at least compatible glycan structures	545:594	authentic or at least compatible glycan structures	545:594	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	4	19	from	plants	691:696	arg1	absence					667:673	the absence	663:673	the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors	663:766	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	4	20	theme	human	624:628	arg1	glycans					630:636	human glycans	624:636	human glycans	624:636	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	5	21	theme	plant	917:921	arg1	glycans					923:929	plant glycans	917:929	plant glycans	917:929	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	6	22	theme	mammalian	1288:1296	arg1	glycans					1308:1314	native mammalian and plant glycans	1281:1314	native mammalian and plant glycans	1281:1314	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	2	23	theme	plant-like	285:294	arg1	glycans					319:325	plant-like rather than human-like glycans	285:325	plant-like rather than human-like glycans	285:325	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	5	24	from	proteins	1011:1018	arg1	presence					982:989	the presence	978:989	the presence of plant glycans on proteins	978:1018	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	4	25	theme	pathway	680:686	arg1	absence					667:673	the absence	663:673	the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors	663:766	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	5	26	theme	functions	1229:1237	arg1	efficacy					1199:1206	the efficacy	1195:1206	the efficacy of antibody effector functions	1195:1237	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	4	27	theme	enzymes	846:852	arg1	expression					817:826	the coordinated expression	801:826	the coordinated expression of multiple human enzymes	801:852	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	5	28	with	removal	906:912	arg1	counterparts					964:975	human counterparts	958:975	human counterparts	958:975	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	4	29	from	pathway	680:686	arg1	plants					691:696	plants	691:696	plants	691:696	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	5	30	with	replacement	941:951	arg1	counterparts					964:975	human counterparts	958:975	human counterparts	958:975	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	4	31	theme	precursors	757:766	arg1	synthesis					706:714	the synthesis	702:714	the synthesis of sialylated proteins and the necessary precursors	702:766	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	5	32	from	glycans	1000:1006	arg1	proteins					1011:1018	proteins	1011:1018	proteins	1011:1018	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	3	33	theme	systems	453:459	arg1	glyco-engineering					409:425	The glyco-engineering	405:425	The glyco-engineering of plant-based expression systems	405:459	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	2	34	contain	carry	279:283	arg2	glycans					319:325	plant-like rather than human-like glycans	285:325	plant-like rather than human-like glycans	285:325	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	2	34	contain	carry	279:283	arg1	proteins					245:252	human therapeutic proteins	227:252	human therapeutic proteins produced in plants	227:271	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	5	35	theme	research	868:875	arg1	community					877:885	the research community	864:885	the research community	864:885	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	4	36	theme	necessary	747:755	arg1	precursors					757:766	the necessary precursors	743:766	the necessary precursors	743:766	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	7	37	contain	contain	1424:1430	arg2	fucose					1432:1437	fucose	1432:1437	fucose	1432:1437	Both glycans contain fucose, albeit with different linkages.
30069741	7	37	contain	contain	1424:1430	arg1	glycans					1416:1422	Both glycans	1411:1422	Both glycans	1411:1422	Both glycans contain fucose, albeit with different linkages.
30069741	0	38	theme	Expression	33:42	arg1	Systems					44:50	Plant-Based Expression Systems	21:50	Plant-Based Expression Systems	21:50	Glyco-Engineering of Plant-Based Expression Systems.
30069741	4	39	theme	coordinated	805:815	arg1	expression					817:826	the coordinated expression	801:826	the coordinated expression of multiple human enzymes	801:852	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	4	40	gly	sialylated	719:728	arg1	proteins					730:737	sialylated proteins	719:737	sialylated proteins	719:737	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	4	41	theme	human	840:844	arg1	enzymes					846:852	multiple human enzymes	831:852	multiple human enzymes	831:852	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	4	42	from	absence	667:673	arg1	plants					691:696	plants	691:696	plants	691:696	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	1	43	theme	species-dependent	190:206	arg1	manner					208:213	a species-dependent manner	188:213	a species-dependent manner	188:213	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	0	44	theme	Plant-Based	21:31	arg1	Systems					44:50	Plant-Based Expression Systems	21:50	Plant-Based Expression Systems	21:50	Glyco-Engineering of Plant-Based Expression Systems.
30069741	4	45	theme	precise	601:607	arg1	replication					609:619	The precise replication	597:619	The precise replication of human glycans	597:636	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	7	46	theme	different	1452:1460	arg1	linkages					1462:1469	different linkages	1452:1469	different linkages	1452:1469	Both glycans contain fucose, albeit with different linkages.
30069741	2	47	theme	human-like	308:317	arg1	glycans					319:325	plant-like rather than human-like glycans	285:325	plant-like rather than human-like glycans	285:325	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	3	48	theme	plant-like	494:503	arg1	glycans					505:511	plant-like glycans	494:511	plant-like glycans	494:511	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	3	49	theme	plant-based	430:440	arg1	systems					453:459	plant-based expression systems	430:459	plant-based expression systems	430:459	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	3	50	theme	human	525:529	arg1	proteins					531:538	human proteins	525:538	human proteins with authentic or at least compatible glycan structures	525:594	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	6	51	theme	Graphical	1240:1248	arg1	structures					1267:1276	Graphical Abstract Typical structures	1240:1276	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues	1240:1353	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	6	52	theme	Typical	1259:1265	arg1	structures					1267:1276	Graphical Abstract Typical structures	1240:1276	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues	1240:1353	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	0	53	theme	Systems	44:50	arg1	Glyco-Engineering					0:16	Glyco-Engineering	0:16	Glyco-Engineering of Plant-Based Expression Systems.	0:51	Glyco-Engineering of Plant-Based Expression Systems.
30069741	3	54	theme	expression	442:451	arg1	systems					453:459	plant-based expression systems	430:459	plant-based expression systems	430:459	The glyco-engineering of plant-based expression systems began as a strategy to eliminate plant-like glycans and produce human proteins with authentic or at least compatible glycan structures.
30069741	2	55	theme	therapeutic	233:243	arg1	proteins					245:252	human therapeutic proteins	227:252	human therapeutic proteins produced in plants	227:271	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	2	56	theme	human	227:231	arg1	proteins					245:252	human therapeutic proteins	227:252	human therapeutic proteins produced in plants	227:271	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	4	57	theme	proteins	730:737	arg1	synthesis					706:714	the synthesis	702:714	the synthesis of sialylated proteins and the necessary precursors	702:766	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	6	58	theme	sugar	1340:1344	arg1	residues					1346:1353	sugar residues	1340:1353	sugar residues	1340:1353	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	4	59	theme	multiple	831:838	arg1	enzymes					846:852	multiple human enzymes	831:852	multiple human enzymes	831:852	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
30069741	2	60	theme	protein	345:351	arg1	stability					353:361	protein stability	345:361	protein stability	345:361	Therefore, human therapeutic proteins produced in plants often carry plant-like rather than human-like glycans, which can affect protein stability, biological function, and immunogenicity.
30069741	5	61	theme	plant	994:998	arg1	glycans					1000:1006	plant glycans	994:1006	plant glycans on proteins	994:1018	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	6	62	theme	Abstract	1250:1257	arg1	structures					1267:1276	Graphical Abstract Typical structures	1240:1276	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues	1240:1353	Graphical Abstract Typical structures of native mammalian and plant glycans with symbols indicating sugar residues identified by their short form and single-letter codes.
30069741	5	63	theme	human	958:962	arg1	counterparts					964:975	human counterparts	958:975	human counterparts	958:975	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	5	64	theme	glycans	1000:1006	arg1	presence					982:989	the presence	978:989	the presence of plant glycans on proteins	978:1018	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	1	65	theme	common	130:135	arg1	steps					150:154	common biosynthesis steps	130:154	common biosynthesis steps	130:154	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	1	66	theme	Most	53:56	arg1	proteins					67:74	Most secreted proteins	53:74	Most secreted proteins in eukaryotes	53:88	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	1	67	theme	biosynthesis	137:148	arg1	steps					150:154	common biosynthesis steps	130:154	common biosynthesis steps	130:154	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	5	68	theme	effector	1220:1227	arg1	functions					1229:1237	antibody effector functions	1211:1237	antibody effector functions	1211:1237	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	1	69	theme	secreted	58:65	arg1	proteins					67:74	Most secreted proteins	53:74	Most secreted proteins in eukaryotes	53:88	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	1	70	theme	steps	150:154	arg1	number					120:125	a number	118:125	a number of common biosynthesis steps	118:154	Most secreted proteins in eukaryotes are glycosylated, and after a number of common biosynthesis steps the glycan structures mature in a species-dependent manner.
30069741	5	71	from	presence	982:989	arg1	proteins					1011:1018	proteins	1011:1018	proteins	1011:1018	Although the research community has focused on the removal of plant glycans and their replacement with human counterparts, the presence of plant glycans on proteins can also provide benefits, such as boosting the immunogenicity of some vaccines, facilitating the interaction between therapeutic proteins and their receptors, and increasing the efficacy of antibody effector functions.
30069741	4	72	theme	sialylated	719:728	arg1	proteins					730:737	sialylated proteins	719:737	sialylated proteins	719:737	The precise replication of human glycans is challenging, owing to the absence of a pathway in plants for the synthesis of sialylated proteins and the necessary precursors, but this can now be achieved by the coordinated expression of multiple human enzymes.
32469948	3	0	theme	expression	336:345	arg1	systems					347:353	Microbial expression systems	326:353	Microbial expression systems	326:353	Microbial expression systems offer economical, rapid and serum-free production and are more amenable to genetic manipulation.
32469948	4	1	theme	gene	516:519	arg1	knockouts					521:529	CRISPR/Cas9 multiple gene knockouts	495:529	CRISPR/Cas9 multiple gene knockouts	495:529	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	1	2	theme	biological	164:173	arg1	activity					175:182	biological activity	164:182	biological activity	164:182	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	6	3	theme	recombination	888:900	arg1	efficiency					902:911	the homologous recombination efficiency	873:911	the homologous recombination efficiency of K. marxianus	873:927	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	4	4	theme	rapid	597:601	arg1	rate					610:613	a rapid growth rate	595:613	a rapid growth rate	595:613	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	6	5	theme	K.	916:917	arg1	efficiency					902:911	the homologous recombination efficiency	873:911	the homologous recombination efficiency of K. marxianus	873:927	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	8	6	theme	Man3GlcNAc2	1206:1216	arg1	Man3GlcNAc2					1206:1216	the core N-glycan Man3GlcNAc2	1188:1216	the core N-glycan Man3GlcNAc2	1188:1216	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	8	6	theme	Man3GlcNAc2	1206:1216	arg1	amounts					1177:1183	low amounts	1173:1183	low amounts	1173:1183	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	8	6	theme	Man3GlcNAc2	1206:1216	arg1	Man3GlcNAc4					1249:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	7	7	theme	N-glycan	1103:1110	arg1	structures					1112:1121	human N-glycan structures	1097:1121	human N-glycan structures	1097:1121	In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures.
32469948	5	8	theme	α-1,6-mannosyltransferase	731:755	arg1	genes					764:768	the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes	690:768	the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes	690:768	As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation.
32469948	7	9	theme	human	1097:1101	arg1	structures					1112:1121	human N-glycan structures	1097:1121	human N-glycan structures	1097:1121	In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures.
32469948	5	10	dep	α-1,3-mannosyltransferase	694:718	arg1	OCH1					758:761	OCH1	758:761	OCH1	758:761	As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation.
32469948	5	10	dep	α-1,3-mannosyltransferase	694:718	arg1	ALG3					721:724	ALG3	721:724	ALG3	721:724	As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation.
32469948	0	11	from	pathway	57:63	arg1	marxianus					82:90	Kluyveromyces marxianus	68:90	Kluyveromyces marxianus	68:90	Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.
32469948	4	12	with	yeast	584:588	arg1	rate					610:613	a rapid growth rate	595:613	a rapid growth rate	595:613	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	2	13	theme	glycan	295:300	arg1	structures					302:311	correct glycan structures	287:311	correct glycan structures	287:311	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	4	14	theme	growth	603:608	arg1	rate					610:613	a rapid growth rate	595:613	a rapid growth rate	595:613	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	6	15	theme	homologous	877:886	arg1	recombination					888:900	homologous recombination	877:900	the homologous recombination efficiency of K. marxianus	873:927	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	2	16	theme	correct	287:293	arg1	structures					302:311	correct glycan structures	287:311	correct glycan structures	287:311	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	8	17	theme	human	1226:1230	arg1	Man3GlcNAc4					1249:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	6	18	dep	K.	916:917	arg1	marxianus					919:927	K. marxianus	916:927	K. marxianus	916:927	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	4	19	theme	multiple	507:514	arg1	knockouts					521:529	CRISPR/Cas9 multiple gene knockouts	495:529	CRISPR/Cas9 multiple gene knockouts	495:529	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	3	20	theme	genetic	430:436	arg1	manipulation					438:449	genetic manipulation	430:449	genetic manipulation	430:449	Microbial expression systems offer economical, rapid and serum-free production and are more amenable to genetic manipulation.
32469948	8	21	theme	low	1173:1175	arg1	Man3GlcNAc2					1206:1216	the core N-glycan Man3GlcNAc2	1188:1216	the core N-glycan Man3GlcNAc2	1188:1216	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	8	21	theme	low	1173:1175	arg1	amounts					1177:1183	low amounts	1173:1183	low amounts	1173:1183	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	8	21	theme	low	1173:1175	arg1	Man3GlcNAc4					1249:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	9	22	theme	engineering	1365:1375	arg1	cornerstone					1336:1346	a cornerstone	1334:1346	a cornerstone of glycosylation engineering in K. marxianus	1334:1391	This study lays a cornerstone of glycosylation engineering in K. marxianus toward producing human glycoproteins.
32469948	4	23	theme	CRISPR/Cas9	495:505	arg1	knockouts					521:529	CRISPR/Cas9 multiple gene knockouts	495:529	CRISPR/Cas9 multiple gene knockouts	495:529	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	7	24	theme	GnTII	1074:1078	arg1	genes					1080:1084	GnTII genes	1074:1084	GnTII genes	1074:1084	In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures.
32469948	5	25	from	problem	651:657	arg1	yeast					662:666	yeast	662:666	yeast	662:666	As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation.
32469948	8	26	theme	N-glycan	1240:1247	arg1	Man3GlcNAc4					1249:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	2	27	gly	glycoproteins	268:280	arg1	glycoproteins					268:280	glycoproteins	268:280	glycoproteins with correct glycan structures	268:311	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	4	28	theme	probiotic	574:582	arg1	marxianus					561:569	Kluyveromyces marxianus	547:569	Kluyveromyces marxianus	547:569	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	4	28	theme	probiotic	574:582	arg1	yeast					584:588	a probiotic yeast	572:588	a probiotic yeast with a rapid growth rate	572:613	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	4	29	from	protocol	482:489	arg1	marxianus					561:569	Kluyveromyces marxianus	547:569	Kluyveromyces marxianus	547:569	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	4	29	from	protocol	482:489	arg1	yeast					584:588	a probiotic yeast	572:588	a probiotic yeast with a rapid growth rate	572:613	In this study, we developed a protocol for CRISPR/Cas9 multiple gene knockouts and knockins in Kluyveromyces marxianus, a probiotic yeast with a rapid growth rate.
32469948	0	30	link	N-linked	34:41	arg1	pathway					57:63	a human complex type N-linked glycosylation pathway	13:63	a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus	13:90	Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.
32469948	6	31	theme	domain	847:852	arg1	subunit					819:825	the subunit	815:825	the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus	815:927	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	8	32	theme	complex	1232:1238	arg1	Man3GlcNAc4					1249:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	0	33	theme	complex	21:27	arg1	pathway					57:63	a human complex type N-linked glycosylation pathway	13:63	a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus	13:90	Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.
32469948	8	34	theme	N-glycan	1197:1204	arg1	Man3GlcNAc2					1206:1216	the core N-glycan Man3GlcNAc2	1188:1216	the core N-glycan Man3GlcNAc2	1188:1216	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	0	35	theme	human	15:19	arg1	pathway					57:63	a human complex type N-linked glycosylation pathway	13:63	a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus	13:90	Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.
32469948	9	36	from	cornerstone	1336:1346	arg1	K.					1380:1381	K.	1380:1381	K.	1380:1381	This study lays a cornerstone of glycosylation engineering in K. marxianus toward producing human glycoproteins.
32469948	1	37	theme	various	118:124	arg1	immunogenicity					189:202	immunogenicity	189:202	immunogenicity	189:202	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	1	37	theme	various	118:124	arg1	properties					134:143	various protein properties	118:143	various protein properties such as stability, biological activity, and immunogenicity	118:202	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	1	37	theme	various	118:124	arg1	stability					153:161	stability	153:161	stability	153:161	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	1	37	theme	various	118:124	arg1	activity					175:182	biological activity	164:182	biological activity	164:182	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	8	38	theme	Man3GlcNAc4	1249:1259	arg1	Man3GlcNAc2					1206:1216	the core N-glycan Man3GlcNAc2	1188:1216	the core N-glycan Man3GlcNAc2	1188:1216	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	8	38	theme	Man3GlcNAc4	1249:1259	arg1	amounts					1177:1183	low amounts	1173:1183	low amounts	1173:1183	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	8	38	theme	Man3GlcNAc4	1249:1259	arg1	Man3GlcNAc4					1249:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	the human complex N-glycan Man3GlcNAc4	1222:1259	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	0	39	theme	N-linked	34:41	arg1	pathway					57:63	a human complex type N-linked glycosylation pathway	13:63	a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus	13:90	Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.
32469948	7	40	theme	β-1,2-N-acetylglucosaminyltransferase	1029:1065	arg1	I					1067:1067	β-1,2-N-acetylglucosaminyltransferase I	1029:1067	β-1,2-N-acetylglucosaminyltransferase I	1029:1067	In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures.
32469948	7	40	theme	β-1,2-N-acetylglucosaminyltransferase	1029:1065	arg1	mannosylation					1001:1013	mannosylation	1001:1013	mannosylation	1001:1013	In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures.
32469948	0	41	theme	type	29:32	arg1	pathway					57:63	a human complex type N-linked glycosylation pathway	13:63	a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus	13:90	Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.
32469948	3	42	dep	economical	361:370	arg1	production					394:403	production	394:403	production	394:403	Microbial expression systems offer economical, rapid and serum-free production and are more amenable to genetic manipulation.
32469948	9	43	dep	K.	1380:1381	arg1	marxianus					1383:1391	K. marxianus	1380:1391	K. marxianus	1380:1391	This study lays a cornerstone of glycosylation engineering in K. marxianus toward producing human glycoproteins.
32469948	9	44	theme	human	1410:1414	arg1	glycoproteins					1416:1428	human glycoproteins	1410:1428	human glycoproteins	1410:1428	This study lays a cornerstone of glycosylation engineering in K. marxianus toward producing human glycoproteins.
32469948	9	45	theme	glycosylation	1351:1363	arg1	engineering					1365:1375	glycosylation engineering	1351:1375	glycosylation engineering	1351:1375	This study lays a cornerstone of glycosylation engineering in K. marxianus toward producing human glycoproteins.
32469948	8	46	theme	core	1192:1195	arg1	Man3GlcNAc2					1206:1216	the core N-glycan Man3GlcNAc2	1188:1216	the core N-glycan Man3GlcNAc2	1188:1216	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	6	47	theme	Ku	844:845	arg1	KU70					855:858	KU70	855:858	KU70	855:858	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	6	47	theme	Ku	844:845	arg1	domain					847:852	the telomeric Ku domain	830:852	the telomeric Ku domain (KU70)	830:859	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	1	48	theme	protein	126:132	arg1	immunogenicity					189:202	immunogenicity	189:202	immunogenicity	189:202	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	1	48	theme	protein	126:132	arg1	properties					134:143	various protein properties	118:143	various protein properties such as stability, biological activity, and immunogenicity	118:202	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	1	48	theme	protein	126:132	arg1	stability					153:161	stability	153:161	stability	153:161	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	1	48	theme	protein	126:132	arg1	activity					175:182	biological activity	164:182	biological activity	164:182	Glycosylation can affect various protein properties such as stability, biological activity, and immunogenicity.
32469948	0	49	theme	glycosylation	43:55	arg1	pathway					57:63	a human complex type N-linked glycosylation pathway	13:63	a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus	13:90	Constructing a human complex type N-linked glycosylation pathway in Kluyveromyces marxianus.
32469948	2	50	with	glycoproteins	268:280	arg1	structures					302:311	correct glycan structures	287:311	correct glycan structures	287:311	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	3	51	theme	Microbial	326:334	arg1	systems					347:353	Microbial expression systems	326:353	Microbial expression systems	326:353	Microbial expression systems offer economical, rapid and serum-free production and are more amenable to genetic manipulation.
32469948	2	52	theme	therapeutic	222:232	arg1	proteins					234:241	human therapeutic proteins	216:241	human therapeutic proteins	216:241	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	2	52	theme	therapeutic	222:232	arg1	host					246:249	a host	244:249	a host that can produce glycoproteins with correct glycan structures	244:311	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	5	53	theme	common	644:649	arg1	problem					651:657	a common problem	642:657	a common problem in yeast	642:666	As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation.
32469948	5	53	theme	common	644:649	arg1	hyper-mannosylation					619:637	hyper-mannosylation	619:637	hyper-mannosylation	619:637	As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation.
32469948	2	54	theme	human	216:220	arg1	proteins					234:241	human therapeutic proteins	216:241	human therapeutic proteins	216:241	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	2	54	theme	human	216:220	arg1	host					246:249	a host	244:249	a host that can produce glycoproteins with correct glycan structures	244:311	To produce human therapeutic proteins, a host that can produce glycoproteins with correct glycan structures is required.
32469948	9	55	gly	glycoproteins	1416:1428	arg1	glycoproteins					1416:1428	human glycoproteins	1410:1428	human glycoproteins	1410:1428	This study lays a cornerstone of glycosylation engineering in K. marxianus toward producing human glycoproteins.
32469948	5	56	theme	α-1,3-mannosyltransferase	694:718	arg1	genes					764:768	the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes	690:768	the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes	690:768	As hyper-mannosylation is a common problem in yeast, we first knocked out the α-1,3-mannosyltransferase (ALG3) and α-1,6-mannosyltransferase (OCH1) genes to reduce mannosylation.
32469948	6	57	theme	telomeric	834:842	arg1	KU70					855:858	KU70	855:858	KU70	855:858	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	6	57	theme	telomeric	834:842	arg1	domain					847:852	the telomeric Ku domain	830:852	the telomeric Ku domain (KU70)	830:859	We also knocked out the subunit of the telomeric Ku domain (KU70) to increase the homologous recombination efficiency of K. marxianus.
32469948	7	58	theme	α-1,2-mannosidase	967:983	arg1	gene					986:989	the MdsI (α-1,2-mannosidase) gene	957:989	the MdsI (α-1,2-mannosidase) gene	957:989	In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures.
32469948	8	59	dep	mannose	1275:1281	arg1	N-acetylglucosamine					1297:1315	N-acetylglucosamine	1297:1315	N-acetylglucosamine	1297:1315	We finally obtained two strains that can produce low amounts of the core N-glycan Man3GlcNAc2 and the human complex N-glycan Man3GlcNAc4, where Man is mannose and GlcNAc is N-acetylglucosamine.
32469948	7	60	theme	MdsI	961:964	arg1	gene					986:989	the MdsI (α-1,2-mannosidase) gene	957:989	the MdsI (α-1,2-mannosidase) gene	957:989	In addition, we knocked in the MdsI (α-1,2-mannosidase) gene to reduce mannosylation and the GnTI (β-1,2-N-acetylglucosaminyltransferase I) and GnTII genes to produce human N-glycan structures.
33135055	6	0	gly	O-glycosylation	883:897	arg2	one					873:875	one	873:875	one	873:875	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	6	0	gly	O-glycosylation	883:897	arg2	site					899:902	one novel O-glycosylation site	873:902	one novel O-glycosylation site	873:902	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	9	1	theme	terminal	1367:1374	arg1	orientations					1376:1387	its terminal orientations	1363:1387	its terminal orientations on the hACE2 receptor	1363:1409	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	7	2	theme	acid	1047:1050	arg1	linkages					1052:1059	the terminal sialic acid linkages	1027:1059	the terminal sialic acid linkages	1027:1059	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	2	theme	acid	1047:1050	arg1	presence					1066:1073	the presence	1062:1073	the presence of bisecting GlcNAc	1062:1093	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	2	theme	acid	1047:1050	arg1	pattern					1103:1109	the pattern	1099:1109	the pattern of N-glycan fucosylation	1099:1134	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	3	3	theme	viral	522:526	arg1	attachment					528:537	viral attachment	522:537	viral attachment	522:537	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	6	4	theme	possible	816:823	arg1	sites					841:845	all seven possible N-glycosylation sites	806:845	all seven possible N-glycosylation sites	806:845	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	7	5	theme	terminal	1031:1038	arg1	linkages					1052:1059	the terminal sialic acid linkages	1027:1059	the terminal sialic acid linkages	1027:1059	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	5	theme	terminal	1031:1038	arg1	presence					1066:1073	the presence	1062:1073	the presence of bisecting GlcNAc	1062:1093	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	5	theme	terminal	1031:1038	arg1	pattern					1103:1109	the pattern	1099:1109	the pattern of N-glycan fucosylation	1099:1134	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	9	6	theme	hACE2	1396:1400	arg1	receptor					1402:1409	the hACE2 receptor	1392:1409	the hACE2 receptor	1392:1409	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	6	7	theme	glycan	771:776	arg1	%					800:800	73.2 to 100%	789:800	73.2 to 100%	789:800	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	6	7	theme	glycan	771:776	arg1	occupancy					778:786	high glycan occupancy	766:786	high glycan occupancy (73.2 to 100%)	766:801	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	7	8	from	epitopes	948:955	arg1	hACE2					960:964	hACE2	960:964	hACE2	960:964	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	1	9	theme	severe	196:201	arg1	coronavirus					230:240	severe acute respiratory syndrome coronavirus 2	196:242	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	196:255	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	1	9	theme	severe	196:201	arg1	SARS-CoV-2					245:254	SARS-CoV-2	245:254	SARS-CoV-2	245:254	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	4	10	theme	angiotensin	610:620	arg1	enzyme					633:638	human angiotensin converting enzyme 2	604:640	human angiotensin converting enzyme 2 (hACE2) for entry	604:658	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	4	10	theme	angiotensin	610:620	arg1	hACE2					643:647	hACE2	643:647	hACE2	643:647	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	7	11	theme	GlcNAc	1088:1093	arg1	linkages					1052:1059	the terminal sialic acid linkages	1027:1059	the terminal sialic acid linkages	1027:1059	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	11	theme	GlcNAc	1088:1093	arg1	presence					1066:1073	the presence	1062:1073	the presence of bisecting GlcNAc	1062:1093	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	11	theme	GlcNAc	1088:1093	arg1	pattern					1103:1109	the pattern	1099:1109	the pattern of N-glycan fucosylation	1099:1134	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	1	12	theme	respiratory	209:219	arg1	coronavirus					230:240	severe acute respiratory syndrome coronavirus 2	196:242	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	196:255	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	1	12	theme	respiratory	209:219	arg1	SARS-CoV-2					245:254	SARS-CoV-2	245:254	SARS-CoV-2	245:254	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	8	13	theme	extensive	1155:1163	arg1	interpretation					1172:1185	extensive manual interpretation	1155:1185	extensive manual interpretation of each glycopeptide and glycan spectrum	1155:1226	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	6	14	theme	O-glycosylation	883:897	arg1	site					899:902	one novel O-glycosylation site	873:902	one novel O-glycosylation site	873:902	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	8	15	gly	glycopeptide	1195:1206	arg2	glycopeptide					1195:1206	each glycopeptide and glycan spectrum	1190:1226	glycopeptide	1195:1206	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	7	16	theme	epitopes	948:955	arg1	structure					928:936	the detailed structure	915:936	the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding	915:1002	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	9	17	theme	hACE2	1439:1443	arg1	sites					1459:1463	hACE2 glycosylation sites	1439:1463	hACE2 glycosylation sites	1439:1463	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	6	18	gly	N-glycosylation	825:839	arg2	sites					841:845	all seven possible N-glycosylation sites	806:845	all seven possible N-glycosylation sites	806:845	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	6	18	gly	N-glycosylation	825:839	arg2	seven					810:814	seven	810:814	seven	810:814	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	9	19	theme	sites	1459:1463	arg1	orientations					1376:1387	its terminal orientations	1363:1387	its terminal orientations on the hACE2 receptor	1363:1409	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	9	19	theme	sites	1459:1463	arg1	elucidation					1312:1322	Our elucidation	1308:1322	Our elucidation of the site-specific glycosylation	1308:1357	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	9	19	theme	sites	1459:1463	arg1	modeling					1427:1434	the modeling	1423:1434	the modeling of hACE2 glycosylation sites	1423:1463	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	8	20	theme	bioinformatics	1250:1263	arg1	tools					1265:1269	bioinformatics tools	1250:1269	bioinformatics tools	1250:1269	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	0	21	theme	SARS-CoV-2	61:70	arg1	enzyme					110:115	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	7	22	theme	detailed	919:926	arg1	structure					928:936	the detailed structure	915:936	the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding	915:1002	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	1	23	theme	disease	153:159	arg1	emergence					124:132	The emergence	120:132	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	120:255	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	0	24	theme	receptor	78:85	arg1	enzyme					110:115	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	9	25	gly	glycosylation	1445:1457	arg2	sites					1459:1463	hACE2 glycosylation sites	1439:1463	hACE2 glycosylation sites	1439:1463	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	0	26	theme	converting	99:108	arg1	enzyme					110:115	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	9	27	theme	intriguing	1494:1503	arg1	interactions					1520:1531	the intriguing virus-receptor interactions	1490:1531	the intriguing virus-receptor interactions	1490:1531	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	7	28	from	hACE2	960:964	arg1	structure					928:936	the detailed structure	915:936	the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding	915:1002	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	5	29	theme	glycoproteomic	694:707	arg1	analysis					709:716	glycomic and glycoproteomic analysis	681:716	analysis	709:716	Herein, we describe glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells.
33135055	0	30	theme	Comprehensive	0:12	arg1	characterization					14:29	Comprehensive characterization	0:29	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.	0:118	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	2	31	theme	such	418:421	arg1	interventions					423:435	such interventions	418:435	such interventions	418:435	Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions.
33135055	3	32	theme	surface	454:460	arg1	features					462:469	The coronavirus surface features	438:469	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion	438:564	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	5	33	theme	HEK293	740:745	arg1	cells					747:751	HEK293 cells	740:751	HEK293 cells	740:751	Herein, we describe glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells.
33135055	7	34	theme	bisecting	1078:1086	arg1	GlcNAc					1088:1093	bisecting GlcNAc	1078:1093	bisecting GlcNAc	1078:1093	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	10	35	theme	pre-existing	1781:1792	arg1	conditions					1794:1803	pre-existing conditions	1781:1803	pre-existing conditions of COVID-19 patients	1781:1824	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	3	36	theme	spike	482:486	arg1	protein					492:498	a trimeric spike (S) protein	471:498	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion	438:564	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	3	36	theme	spike	482:486	arg1	essential					508:516	essential	508:516	essential	508:516	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	1	37	theme	therapeutic	301:311	arg1	strategies					313:322	new therapeutic strategies	297:322	new therapeutic strategies	297:322	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	9	38	theme	therapeutics	1572:1583	arg1	development					1551:1561	the development	1547:1561	the development of novel therapeutics	1547:1583	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	1	39	theme	syndrome	221:228	arg1	coronavirus					230:240	severe acute respiratory syndrome coronavirus 2	196:242	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	196:255	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	1	39	theme	syndrome	221:228	arg1	SARS-CoV-2					245:254	SARS-CoV-2	245:254	SARS-CoV-2	245:254	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	4	40	theme	S	571:571	arg1	protein					573:579	The S protein	567:579	The S protein of SARS-CoV-2	567:593	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	3	41	theme	coronavirus	442:452	arg1	features					462:469	The coronavirus surface features	438:469	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion	438:564	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	9	42	dep	along	1412:1416	arg1	with					1418:1421	with	1418:1421	with	1418:1421	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	10	43	theme	recent	1685:1690	arg1	reports					1692:1698	some recent reports	1680:1698	some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients	1680:1824	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	8	44	theme	manual	1165:1170	arg1	interpretation					1172:1185	extensive manual interpretation	1155:1185	extensive manual interpretation of each glycopeptide and glycan spectrum	1155:1226	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	9	45	theme	glycosylation	1345:1357	arg1	orientations					1376:1387	its terminal orientations	1363:1387	its terminal orientations on the hACE2 receptor	1363:1409	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	9	45	theme	glycosylation	1345:1357	arg1	elucidation					1312:1322	Our elucidation	1308:1322	Our elucidation of the site-specific glycosylation	1308:1357	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	9	45	theme	glycosylation	1345:1357	arg1	modeling					1427:1434	the modeling	1423:1434	the modeling of hACE2 glycosylation sites	1423:1463	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	3	46	dep	features	462:469	arg1	protein					492:498	a trimeric spike (S) protein	471:498	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion	438:564	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	3	46	dep	features	462:469	arg1	essential					508:516	essential	508:516	essential	508:516	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	5	47	theme	hACE2	721:725	arg1	analysis					709:716	glycomic and glycoproteomic analysis	681:716	analysis	709:716	Herein, we describe glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells.
33135055	2	48	theme	viral	351:355	arg1	attachment					357:366	viral attachment	351:366	viral attachment	351:366	Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions.
33135055	7	49	theme	sialic	1040:1045	arg1	linkages					1052:1059	the terminal sialic acid linkages	1027:1059	the terminal sialic acid linkages	1027:1059	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	49	theme	sialic	1040:1045	arg1	presence					1066:1073	the presence	1062:1073	the presence of bisecting GlcNAc	1062:1093	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	49	theme	sialic	1040:1045	arg1	pattern					1103:1109	the pattern	1099:1109	the pattern of N-glycan fucosylation	1099:1134	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	6	50	theme	high	766:769	arg1	%					800:800	73.2 to 100%	789:800	73.2 to 100%	789:800	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	6	50	theme	high	766:769	arg1	occupancy					778:786	high glycan occupancy	766:786	high glycan occupancy (73.2 to 100%)	766:801	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	10	51	theme	varying	1710:1716	arg1	complications					1733:1745	the varying ACE2 dependent complications	1706:1745	the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients	1706:1824	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	6	52	theme	N-glycosylation	825:839	arg1	sites					841:845	all seven possible N-glycosylation sites	806:845	all seven possible N-glycosylation sites	806:845	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	7	53	from	structure	928:936	arg1	hACE2					960:964	hACE2	960:964	hACE2	960:964	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	4	54	theme	converting	622:631	arg1	enzyme					633:638	human angiotensin converting enzyme 2	604:640	human angiotensin converting enzyme 2 (hACE2) for entry	604:658	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	4	54	theme	converting	622:631	arg1	hACE2					643:647	hACE2	643:647	hACE2	643:647	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	1	55	theme	pandemic	177:184	arg1	disease					153:159	the coronavirus disease	137:159	the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	137:255	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	8	56	dep	using	1244:1248	arg1	addition					1232:1239	addition	1232:1239	addition	1232:1239	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	10	57	theme	dependent	1723:1731	arg1	complications					1733:1745	the varying ACE2 dependent complications	1706:1745	the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients	1706:1824	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	8	58	theme	glycopeptide	1195:1206	arg1	spectrum					1219:1226	each glycopeptide and glycan spectrum	1190:1226	spectrum	1219:1226	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	7	59	theme	viral	990:994	arg1	binding					996:1002	viral binding	990:1002	viral binding	990:1002	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	1	60	theme	acute	203:207	arg1	coronavirus					230:240	severe acute respiratory syndrome coronavirus 2	196:242	severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	196:255	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	1	60	theme	acute	203:207	arg1	SARS-CoV-2					245:254	SARS-CoV-2	245:254	SARS-CoV-2	245:254	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	8	61	theme	glycan	1212:1217	arg1	spectrum					1219:1226	each glycopeptide and glycan spectrum	1190:1226	spectrum	1219:1226	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	7	62	theme	fucosylation	1123:1134	arg1	linkages					1052:1059	the terminal sialic acid linkages	1027:1059	the terminal sialic acid linkages	1027:1059	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	62	theme	fucosylation	1123:1134	arg1	presence					1066:1073	the presence	1062:1073	the presence of bisecting GlcNAc	1062:1093	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	7	62	theme	fucosylation	1123:1134	arg1	pattern					1103:1109	the pattern	1099:1109	the pattern of N-glycan fucosylation	1099:1134	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	3	63	theme	membrane	550:557	arg1	fusion					559:564	membrane fusion	550:564	membrane fusion	550:564	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	6	64	theme	novel	877:881	arg1	site					899:902	one novel O-glycosylation site	873:902	one novel O-glycosylation site	873:902	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	9	65	theme	glycosylation	1445:1457	arg1	sites					1459:1463	hACE2 glycosylation sites	1439:1463	hACE2 glycosylation sites	1439:1463	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	0	66	theme	human	72:76	arg1	enzyme					110:115	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	7	67	theme	glycan	941:946	arg1	epitopes					948:955	glycan epitopes	941:955	glycan epitopes on hACE2	941:964	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	1	68	theme	coronavirus	141:151	arg1	disease					153:159	the coronavirus disease	137:159	the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	137:255	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	5	69	theme	glycomic	681:688	arg1	analysis					709:716	glycomic and glycoproteomic analysis	681:716	analysis	709:716	Herein, we describe glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells.
33135055	0	70	theme	angiotensin	87:97	arg1	enzyme					110:115	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	SARS-CoV-2 human receptor angiotensin converting enzyme 2	61:117	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	9	71	from	elucidation	1312:1322	arg1	receptor					1402:1409	the hACE2 receptor	1392:1409	the hACE2 receptor	1392:1409	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	0	72	theme	enzyme	110:115	arg1	O-					41:42	O-	41:42	O-	41:42	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	0	72	theme	enzyme	110:115	arg1	N-					34:35	N-	34:35	N-	34:35	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	10	73	theme	ACE2	1647:1650	arg1	role					1639:1642	the role	1635:1642	the role of ACE2	1635:1650	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	3	74	dep	spike	482:486	arg1	S					489:489	S	489:489	S	489:489	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	8	75	theme	hACE2	1287:1291	arg1	glycosylation					1293:1305	the hACE2 glycosylation	1283:1305	the hACE2 glycosylation	1283:1305	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	2	76	theme	replication	379:389	arg1	mode					343:346	the mode	339:346	the mode of viral attachment, entry and replication	339:389	Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions.
33135055	2	77	theme	interventions	423:435	arg1	aspect					408:413	a key aspect	402:413	a key aspect of such interventions	402:435	Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions.
33135055	10	78	theme	patients	1817:1824	arg1	age					1762:1764	age	1762:1764	age	1762:1764	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	10	78	theme	patients	1817:1824	arg1	race					1772:1775	race	1772:1775	race	1772:1775	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	10	78	theme	patients	1817:1824	arg1	conditions					1794:1803	pre-existing conditions	1781:1803	pre-existing conditions of COVID-19 patients	1781:1824	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	10	78	theme	patients	1817:1824	arg1	sex					1767:1769	sex	1767:1769	sex	1767:1769	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	2	79	theme	entry	369:373	arg1	mode					343:346	the mode	339:346	the mode of viral attachment, entry and replication	339:389	Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions.
33135055	0	80	theme	N-	34:35	arg1	characterization					14:29	Comprehensive characterization	0:29	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.	0:118	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	9	81	from	orientations	1376:1387	arg1	receptor					1402:1409	the hACE2 receptor	1392:1409	the hACE2 receptor	1392:1409	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	9	82	theme	virus-receptor	1505:1518	arg1	interactions					1520:1531	the intriguing virus-receptor interactions	1490:1531	the intriguing virus-receptor interactions	1490:1531	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	10	83	theme	COVID-19	1808:1815	arg1	patients					1817:1824	COVID-19 patients	1808:1824	COVID-19 patients	1808:1824	The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race and pre-existing conditions of COVID-19 patients.
33135055	2	84	theme	key	404:406	arg1	aspect					408:413	a key aspect	402:413	a key aspect of such interventions	402:435	Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions.
33135055	0	85	theme	O-	41:42	arg1	characterization					14:29	Comprehensive characterization	0:29	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.	0:118	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	8	86	theme	spectrum	1219:1226	arg1	interpretation					1172:1185	extensive manual interpretation	1155:1185	extensive manual interpretation of each glycopeptide and glycan spectrum	1155:1226	We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation.
33135055	6	87	dep	%	800:800	arg1	to					794:795	to	794:795	to	794:795	We observed high glycan occupancy (73.2 to 100%) at all seven possible N-glycosylation sites and surprisingly detected one novel O-glycosylation site.
33135055	7	88	theme	N-glycan	1114:1121	arg1	fucosylation					1123:1134	N-glycan fucosylation	1114:1134	N-glycan fucosylation	1114:1134	To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc and the pattern of N-glycan fucosylation.
33135055	1	89	theme	new	297:299	arg1	strategies					313:322	new therapeutic strategies	297:322	new therapeutic strategies	297:322	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	9	90	theme	novel	1566:1570	arg1	therapeutics					1572:1583	novel therapeutics	1566:1583	novel therapeutics	1566:1583	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	9	91	from	modeling	1427:1434	arg1	receptor					1402:1409	the hACE2 receptor	1392:1409	the hACE2 receptor	1392:1409	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	1	92	theme	strategies	313:322	arg1	development					282:292	development	282:292	development of new therapeutic strategies	282:322	The emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created the need for development of new therapeutic strategies.
33135055	0	93	dep	N-	34:35	arg1	glycosylation					44:56	glycosylation	44:56	glycosylation	44:56	Comprehensive characterization of N- and O- glycosylation of SARS-CoV-2 human receptor angiotensin converting enzyme 2.
33135055	3	94	theme	trimeric	473:480	arg1	protein					492:498	a trimeric spike (S) protein	471:498	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion	438:564	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	3	94	theme	trimeric	473:480	arg1	essential					508:516	essential	508:516	essential	508:516	The coronavirus surface features a trimeric spike (S) protein that is essential for viral attachment, entry and membrane fusion.
33135055	9	95	theme	site-specific	1331:1343	arg1	glycosylation					1345:1357	the site-specific glycosylation	1327:1357	the site-specific glycosylation	1327:1357	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	4	96	theme	human	604:608	arg1	enzyme					633:638	human angiotensin converting enzyme 2	604:640	human angiotensin converting enzyme 2 (hACE2) for entry	604:658	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	4	96	theme	human	604:608	arg1	hACE2					643:647	hACE2	643:647	hACE2	643:647	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	9	97	theme	viral	1596:1600	arg1	entry					1602:1606	viral entry	1596:1606	viral entry	1596:1606	Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry.
33135055	4	98	theme	SARS-CoV-2	584:593	arg1	protein					573:579	The S protein	567:579	The S protein of SARS-CoV-2	567:593	The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry.
33135055	2	99	theme	attachment	357:366	arg1	mode					343:346	the mode	339:346	the mode of viral attachment, entry and replication	339:389	Understanding the mode of viral attachment, entry and replication has become a key aspect of such interventions.
31879931	7	0	theme	method	1202:1207	arg1	procedures					1168:1177	detailed procedures	1159:1177	detailed procedures of this chemoenzymatic method	1159:1207	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	6	1	theme	GlcNAc	797:802	arg1	peptide					804:810	the GlcNAc peptide	793:810	the GlcNAc peptide	793:810	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	3	2	theme	Various	368:374	arg1	methods					404:410	Various chemical and chemoenzymatic methods	368:410	Various chemical and chemoenzymatic methods	368:410	Various chemical and chemoenzymatic methods have been reported so far for synthesizing different N- and O-glycopeptides.
31879931	4	3	theme	N-glycans	582:590	arg1	ligation					565:572	an endoglycosidase-catalyzed ligation	536:572	an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides	536:617	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	8	4	theme	other	1427:1431	arg1	N-glycopeptides					1456:1470	other biologically important N-glycopeptides	1427:1470	other biologically important N-glycopeptides	1427:1470	The described procedures should be generally applicable for the synthesis of other biologically important N-glycopeptides.
31879931	4	5	theme	efficient	643:651	arg1	method					653:658	a highly efficient method	634:658	a highly efficient method for constructing large complex N-glycopeptides	634:705	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	4	6	theme	free	577:580	arg1	N-glycans					582:590	free N-glycans	577:590	free N-glycans	577:590	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	5	7	theme	key	753:755	arg1	steps					757:761	two key steps	749:761	two key steps	749:761	This chemoenzymatic approach consists of two key steps.
31879931	6	8	theme	GlcNAc	898:903	arg1	moiety					905:910	an Asn-linked GlcNAc moiety	884:910	an Asn-linked GlcNAc moiety	884:910	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	2	9	theme	functional	320:329	arg1	studies					331:337	functional studies	320:337	functional studies	320:337	Structurally well-defined homogeneous glycopeptides are highly demanded for functional studies and biomedical applications.
31879931	7	10	theme	chemoenzymatic	1187:1200	arg1	method					1202:1207	this chemoenzymatic method	1182:1207	this chemoenzymatic method	1182:1207	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	4	11	gly	N-glycopeptides	691:705	arg2	N-glycopeptides					691:705	large complex N-glycopeptides	677:705	large complex N-glycopeptides	677:705	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	8	12	theme	important	1446:1454	arg1	N-glycopeptides					1456:1470	other biologically important N-glycopeptides	1427:1470	other biologically important N-glycopeptides	1427:1470	The described procedures should be generally applicable for the synthesis of other biologically important N-glycopeptides.
31879931	6	13	theme	GlcNAc	1055:1060	arg1	peptide					1062:1068	the GlcNAc peptide	1051:1068	the GlcNAc peptide	1051:1068	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	3	14	theme	chemoenzymatic	389:402	arg1	methods					404:410	Various chemical and chemoenzymatic methods	368:410	Various chemical and chemoenzymatic methods	368:410	Various chemical and chemoenzymatic methods have been reported so far for synthesizing different N- and O-glycopeptides.
31879931	7	15	theme	HIV-1	1247:1251	arg1	antigens					1269:1276	two HIV-1 V3 glycopeptide antigens	1243:1276	two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively	1243:1347	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	6	16	theme	efficient	1099:1107	arg1	mutant					1123:1128	its efficient glycosynthase mutant	1095:1128	its efficient glycosynthase mutant	1095:1128	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	17	gly	glycosylation	931:943	arg2	site					945:948	a predetermined glycosylation site	915:948	a predetermined glycosylation site	915:948	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	4	18	theme	endoglycosidase-catalyzed	539:563	arg1	ligation					565:572	an endoglycosidase-catalyzed ligation	536:572	an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides	536:617	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	5	19	theme	chemoenzymatic	713:726	arg1	approach					728:735	This chemoenzymatic approach	708:735	This chemoenzymatic approach	708:735	This chemoenzymatic approach consists of two key steps.
31879931	4	20	theme	large	677:681	arg1	N-glycopeptides					691:705	large complex N-glycopeptides	677:705	large complex N-glycopeptides	677:705	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	1	21	theme	inherent	179:186	arg1	properties					188:197	inherent properties	179:197	inherent properties	179:197	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	2	22	gly	glycopeptides	282:294	arg2	glycopeptides					282:294	Structurally well-defined homogeneous glycopeptides	244:294	Structurally well-defined homogeneous glycopeptides	244:294	Structurally well-defined homogeneous glycopeptides are highly demanded for functional studies and biomedical applications.
31879931	6	23	theme	second	959:964	arg1	step					966:969	the second step	955:969	the second step	955:969	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	24	link	Asn-linked	887:896	arg1	moiety					905:910	an Asn-linked GlcNAc moiety	884:910	an Asn-linked GlcNAc moiety	884:910	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	7	25	theme	V3	1253:1254	arg1	antigens					1269:1276	two HIV-1 V3 glycopeptide antigens	1243:1276	two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively	1243:1347	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	0	26	theme	Chemoenzymatic	0:13	arg1	Synthesis					15:23	Chemoenzymatic Synthesis	0:23	Chemoenzymatic Synthesis of HIV-1 Glycopeptide Antigens	0:54	Chemoenzymatic Synthesis of HIV-1 Glycopeptide Antigens.
31879931	7	27	theme	detailed	1159:1166	arg1	procedures					1168:1177	detailed procedures	1159:1177	detailed procedures of this chemoenzymatic method	1159:1207	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	2	28	theme	biomedical	343:352	arg1	applications					354:365	biomedical applications	343:365	biomedical applications	343:365	Structurally well-defined homogeneous glycopeptides are highly demanded for functional studies and biomedical applications.
31879931	0	29	theme	HIV-1	28:32	arg1	Antigens					47:54	HIV-1 Glycopeptide Antigens	28:54	HIV-1 Glycopeptide Antigens	28:54	Chemoenzymatic Synthesis of HIV-1 Glycopeptide Antigens.
31879931	8	30	gly	N-glycopeptides	1456:1470	arg2	N-glycopeptides					1456:1470	other biologically important N-glycopeptides	1427:1470	other biologically important N-glycopeptides	1427:1470	The described procedures should be generally applicable for the synthesis of other biologically important N-glycopeptides.
31879931	6	31	from	bloc	1043:1046	arg1	N-glycan					989:996	an N-glycan	986:996	an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide	986:1068	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	1	32	theme	posttranslational	97:113	arg1	modifications					115:127	the most common posttranslational modifications	81:127	the most common posttranslational modifications of proteins	81:139	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	6	33	theme	first	768:772	arg1	step					774:777	The first step	764:777	The first step	764:777	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	1	34	theme	biological	203:212	arg1	functions					214:222	biological functions	203:222	biological functions	203:222	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	1	35	theme	common	90:95	arg1	modifications					115:127	the most common posttranslational modifications	81:127	the most common posttranslational modifications of proteins	81:139	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	4	36	theme	complex	683:689	arg1	N-glycopeptides					691:705	large complex N-glycopeptides	677:705	large complex N-glycopeptides	677:705	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	1	37	theme	modifications	115:127	arg1	one					74:76	one	74:76	one	74:76	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	1	37	theme	modifications	115:127	arg1	modifications					115:127	the most common posttranslational modifications	81:127	the most common posttranslational modifications of proteins	81:139	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	8	38	theme	described	1354:1362	arg1	procedures					1364:1373	The described procedures	1350:1373	The described procedures	1350:1373	The described procedures should be generally applicable for the synthesis of other biologically important N-glycopeptides.
31879931	8	38	theme	described	1354:1362	arg1	applicable					1395:1404	applicable	1395:1404	applicable	1395:1404	The described procedures should be generally applicable for the synthesis of other biologically important N-glycopeptides.
31879931	0	39	theme	Antigens	47:54	arg1	Synthesis					15:23	Chemoenzymatic Synthesis	0:23	Chemoenzymatic Synthesis of HIV-1 Glycopeptide Antigens	0:54	Chemoenzymatic Synthesis of HIV-1 Glycopeptide Antigens.
31879931	6	40	theme	en	1040:1041	arg1	bloc					1043:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	7	41	theme	glycopeptide	1256:1267	arg1	antigens					1269:1276	two HIV-1 V3 glycopeptide antigens	1243:1276	two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively	1243:1347	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	1	42	dep	properties	188:197	arg1	the					175:177	the	175:177	the	175:177	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	0	43	theme	Glycopeptide	34:45	arg1	Antigens					47:54	HIV-1 Glycopeptide Antigens	28:54	HIV-1 Glycopeptide Antigens	28:54	Chemoenzymatic Synthesis of HIV-1 Glycopeptide Antigens.
31879931	4	44	theme	GlcNAc-tagged	596:608	arg1	peptides					610:617	GlcNAc-tagged peptides	596:617	GlcNAc-tagged peptides	596:617	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	7	45	contain	carrying	1278:1285	arg2	N-glycan					1326:1333	a complex-type N-glycan	1311:1333	a complex-type N-glycan	1311:1333	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	7	45	contain	carrying	1278:1285	arg1	antigens					1269:1276	two HIV-1 V3 glycopeptide antigens	1243:1276	two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively	1243:1347	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	7	45	contain	carrying	1278:1285	arg2	high-mannose-type					1289:1305	a high-mannose-type	1287:1305	a high-mannose-type	1287:1305	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	4	46	theme	peptides	610:617	arg1	ligation					565:572	an endoglycosidase-catalyzed ligation	536:572	an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides	536:617	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	6	47	theme	N-glycan	1021:1028	arg1	bloc					1043:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	48	theme	Asn-linked	887:896	arg1	moiety					905:910	an Asn-linked GlcNAc moiety	884:910	an Asn-linked GlcNAc moiety	884:910	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	4	49	theme	chemoenzymatic	505:518	arg1	method					520:525	the chemoenzymatic method	501:525	the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides	501:617	Among them, the chemoenzymatic method based on an endoglycosidase-catalyzed ligation of free N-glycans and GlcNAc-tagged peptides is emerging as a highly efficient method for constructing large complex N-glycopeptides.
31879931	3	50	theme	different	455:463	arg1	N-					465:466	N-	465:466	N-	465:466	Various chemical and chemoenzymatic methods have been reported so far for synthesizing different N- and O-glycopeptides.
31879931	6	51	theme	corresponding	1007:1019	arg1	bloc					1043:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	7	52	theme	complex-type	1313:1324	arg1	N-glycan					1326:1333	a complex-type N-glycan	1311:1333	a complex-type N-glycan	1311:1333	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	6	53	theme	glycosylation	931:943	arg1	site					945:948	a predetermined glycosylation site	915:948	a predetermined glycosylation site	915:948	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	54	theme	peptide	842:848	arg1	SPPS					861:864	SPPS	861:864	SPPS	861:864	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	54	theme	peptide	842:848	arg1	synthesis					850:858	automated solid-phase peptide synthesis	820:858	automated solid-phase peptide synthesis (SPPS)	820:865	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	1	55	theme	proteins	132:139	arg1	modifications					115:127	the most common posttranslational modifications	81:127	the most common posttranslational modifications of proteins	81:139	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	2	56	theme	well-defined	257:268	arg1	glycopeptides					282:294	Structurally well-defined homogeneous glycopeptides	244:294	Structurally well-defined homogeneous glycopeptides	244:294	Structurally well-defined homogeneous glycopeptides are highly demanded for functional studies and biomedical applications.
31879931	6	57	theme	oxazoline	1030:1038	arg1	bloc					1043:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	the corresponding N-glycan oxazoline en bloc	1003:1046	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	58	theme	predetermined	917:929	arg1	site					945:948	a predetermined glycosylation site	915:948	a predetermined glycosylation site	915:948	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	7	59	gly	glycopeptide	1256:1267	arg2	glycopeptide					1256:1267	two HIV-1 V3 glycopeptide antigens	1243:1276	two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively	1243:1347	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	6	60	theme	solid-phase	830:840	arg1	SPPS					861:864	SPPS	861:864	SPPS	861:864	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	60	theme	solid-phase	830:840	arg1	synthesis					850:858	automated solid-phase peptide synthesis	820:858	automated solid-phase peptide synthesis (SPPS)	820:865	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	1	61	theme	given	229:233	arg1	protein					235:241	a given protein	227:241	a given protein	227:241	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	8	62	theme	N-glycopeptides	1456:1470	arg1	synthesis					1414:1422	the synthesis	1410:1422	the synthesis of other biologically important N-glycopeptides	1410:1470	The described procedures should be generally applicable for the synthesis of other biologically important N-glycopeptides.
31879931	6	63	theme	automated	820:828	arg1	SPPS					861:864	SPPS	861:864	SPPS	861:864	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	6	63	theme	automated	820:828	arg1	synthesis					850:858	automated solid-phase peptide synthesis	820:858	automated solid-phase peptide synthesis (SPPS)	820:865	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	1	64	theme	protein	235:241	arg1	properties					188:197	inherent properties	179:197	inherent properties	179:197	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	1	64	theme	protein	235:241	arg1	functions					214:222	biological functions	203:222	biological functions	203:222	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
31879931	3	65	theme	chemical	376:383	arg1	methods					404:410	Various chemical and chemoenzymatic methods	368:410	Various chemical and chemoenzymatic methods	368:410	Various chemical and chemoenzymatic methods have been reported so far for synthesizing different N- and O-glycopeptides.
31879931	6	66	theme	glycosynthase	1109:1121	arg1	mutant					1123:1128	its efficient glycosynthase mutant	1095:1128	its efficient glycosynthase mutant	1095:1128	The first step is to prepare the GlcNAc peptide through automated solid-phase peptide synthesis (SPPS) by incorporating an Asn-linked GlcNAc moiety at a predetermined glycosylation site; and the second step is to transfer an N-glycan from the corresponding N-glycan oxazoline en bloc to the GlcNAc peptide by an endoglycosidase or its efficient glycosynthase mutant.
31879931	2	67	theme	homogeneous	270:280	arg1	glycopeptides					282:294	Structurally well-defined homogeneous glycopeptides	244:294	Structurally well-defined homogeneous glycopeptides	244:294	Structurally well-defined homogeneous glycopeptides are highly demanded for functional studies and biomedical applications.
31879931	7	68	theme	antigens	1269:1276	arg1	synthesis					1230:1238	the synthesis	1226:1238	the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively	1226:1347	In this chapter, we provide detailed procedures of this chemoenzymatic method by demonstrating the synthesis of two HIV-1 V3 glycopeptide antigens carrying a high-mannose-type and a complex-type N-glycan, respectively.
31879931	3	69	gly	O-glycopeptides	472:486	arg2	O-glycopeptides					472:486	O-glycopeptides	472:486	O-glycopeptides	472:486	Various chemical and chemoenzymatic methods have been reported so far for synthesizing different N- and O-glycopeptides.
31879931	1	70	theme	profound	155:162	arg1	effects					164:170	profound effects	155:170	profound effects	155:170	Glycosylation is one of the most common posttranslational modifications of proteins and can exert profound effects on the inherent properties and biological functions of a given protein.
33581334	7	0	dep	https	876:880	arg1	//www.oglyp.org/					882:897	//www.oglyp.org/	882:897	//www.oglyp.org/	882:897	Moreover, an OGP-based website is already available (https://www.oglyp.org/).
33581334	1	1	theme	clinical	161:168	arg1	trials					170:175	clinical trials	161:175	clinical trials	161:175	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	9	2	theme	protein	1177:1183	arg1	Nos.					1195:1198	protein accession Nos.	1177:1198	protein accession Nos.	1177:1198	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	11	3	dep	website	1514:1520	arg1	https					1523:1527	https	1523:1527	https://www.oglyp.org/download.php	1523:1556	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	5	4	theme	largest	679:685	arg1	it					669:670	it	669:670	it	669:670	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	5	4	theme	largest	679:685	arg1	O-glycoprotein					687:700	the largest O-glycoprotein	675:700	the largest O-glycoprotein repository thus far	675:720	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	5	5	theme	repository	702:711	arg1	it					669:670	it	669:670	it	669:670	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	5	5	theme	repository	702:711	arg1	O-glycoprotein					687:700	the largest O-glycoprotein	675:700	the largest O-glycoprotein repository thus far	675:720	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	11	6	theme	OGP	1510:1512	arg1	website					1514:1520	OGP website	1510:1520	OGP website (https://www.oglyp.org/download.php)	1510:1557	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	4	7	theme	data	528:531	arg1	collection					499:508	a collection	497:508	a collection of O-glycoprotein data from different sources	497:554	It was constructed with a collection of O-glycoprotein data from different sources.
33581334	8	8	theme	site	1013:1016	arg1	modules					965:971	four specially designed and user-friendly modules	923:971	four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission	923:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	8	theme	site	1013:1016	arg1	prediction					1018:1027	site prediction	1013:1027	site prediction	1013:1027	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	9	dep	modules	965:971	arg1	submission					1039:1048	data submission	1034:1048	data submission	1034:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	9	dep	modules	965:971	arg1	modules					965:971	four specially designed and user-friendly modules	923:971	four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission	923:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	9	dep	modules	965:971	arg1	analysis					986:993	statistical analysis	974:993	statistical analysis	974:993	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	9	dep	modules	965:971	arg1	search					1005:1010	database search	996:1010	database search	996:1010	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	9	dep	modules	965:971	arg1	prediction					1018:1027	site prediction	1013:1027	site prediction	1013:1027	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	10	theme	database	996:1003	arg1	modules					965:971	four specially designed and user-friendly modules	923:971	four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission	923:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	10	theme	database	996:1003	arg1	search					1005:1010	database search	996:1010	database search	996:1010	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	3	11	gly	O-glycoprotein	407:420	arg1	O-glycoprotein					407:420	an O-glycoprotein repository	404:431	an O-glycoprotein repository named OGP	404:441	To resolve this issue, an O-glycoprotein repository named OGP was established in this work.
33581334	5	12	theme	2133	643:646	arg1	O-glycoproteins					648:662	2133 O-glycoproteins	643:662	2133 O-glycoproteins	643:662	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	2	13	theme	databases	302:310	arg1	lack					271:274	the lack	267:274	the lack of updated and convenient databases	267:310	However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data.
33581334	6	14	theme	O-glycosylation	745:759	arg1	sites					761:765	the recorded O-glycosylation sites	732:765	the recorded O-glycosylation sites	732:765	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	5	15	contain	contains	561:568	arg2	sites					591:595	9354 O-glycosylation sites	570:595	9354 O-glycosylation sites	570:595	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	5	15	contain	contains	561:568	arg1	OGP					557:559	OGP	557:559	OGP	557:559	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	5	15	contain	contains	561:568	arg2	O-glycans					622:630	11,633 site-specific O-glycans	601:630	11,633 site-specific O-glycans mapping to 2133 O-glycoproteins	601:662	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	8	16	theme	data	1034:1037	arg1	submission					1039:1048	data submission	1034:1048	data submission	1034:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	16	theme	data	1034:1037	arg1	modules					965:971	four specially designed and user-friendly modules	923:971	four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission	923:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	4	17	from	collection	499:508	arg1	sources					548:554	different sources	538:554	different sources	538:554	It was constructed with a collection of O-glycoprotein data from different sources.
33581334	6	18	theme	recorded	736:743	arg1	sites					761:765	the recorded O-glycosylation sites	732:765	the recorded O-glycosylation sites	732:765	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	2	19	theme	convenient	291:300	arg1	databases					302:310	updated and convenient databases	279:310	updated and convenient databases	279:310	However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data.
33581334	4	20	gly	O-glycoprotein	513:526	arg1	O-glycoprotein					513:526	O-glycoprotein data	513:531	O-glycoprotein data from different sources	513:554	It was constructed with a collection of O-glycoprotein data from different sources.
33581334	9	21	gly	O-glycosylation	1201:1215	arg2	sites					1217:1221	O-glycosylation sites	1201:1221	O-glycosylation sites	1201:1221	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	22	theme	O-glycan	1264:1271	arg1	sequences					1239:1247	O-glycopeptide sequences	1224:1247	O-glycopeptide sequences	1224:1247	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	22	theme	O-glycan	1264:1271	arg1	structures					1273:1282	site-specific O-glycan structures	1250:1282	site-specific O-glycan structures	1250:1282	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	23	theme	site-specific	1250:1262	arg1	sequences					1239:1247	O-glycopeptide sequences	1224:1247	O-glycopeptide sequences	1224:1247	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	23	theme	site-specific	1250:1262	arg1	structures					1273:1282	site-specific O-glycan structures	1250:1282	site-specific O-glycan structures	1250:1282	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	1	24	theme	necessitated	182:193	arg1	analysis					221:228	necessitated comprehensive and precise analysis	182:228	necessitated comprehensive and precise analysis of protein O-glycosylation	182:255	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	9	25	gly	O-glycopeptide	1224:1237	arg2	O-glycopeptide					1224:1237	O-glycopeptide sequences	1224:1247	O-glycopeptide sequences	1224:1247	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	7	26	theme	OGP-based	836:844	arg1	https					876:880	https	876:880	https://www.oglyp.org/	876:897	Moreover, an OGP-based website is already available (https://www.oglyp.org/).
33581334	7	26	theme	OGP-based	836:844	arg1	website					846:852	an OGP-based website	833:852	an OGP-based website	833:852	Moreover, an OGP-based website is already available (https://www.oglyp.org/).
33581334	7	26	theme	OGP-based	836:844	arg1	available					865:873	available	865:873	available	865:873	Moreover, an OGP-based website is already available (https://www.oglyp.org/).
33581334	5	27	theme	11,633	601:606	arg1	O-glycans					622:630	11,633 site-specific O-glycans	601:630	11,633 site-specific O-glycans mapping to 2133 O-glycoproteins	601:662	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	10	28	theme	O-glycosylation	1344:1358	arg1	data					1360:1363	O-glycosylation data	1344:1363	O-glycosylation data mining	1344:1370	O-glycosylation data mining can be performed efficiently on this website, which will greatly facilitate related studies.
33581334	1	29	theme	comprehensive	195:207	arg1	analysis					221:228	necessitated comprehensive and precise analysis	182:228	necessitated comprehensive and precise analysis of protein O-glycosylation	182:255	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	9	30	gly	O-glycosylation	1321:1335	arg2	sites					1337:1341	potential O-glycosylation sites	1311:1341	potential O-glycosylation sites	1311:1341	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	31	theme	O-glycopeptide	1224:1237	arg1	sequences					1239:1247	O-glycopeptide sequences	1224:1247	O-glycopeptide sequences	1224:1247	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	31	theme	O-glycopeptide	1224:1237	arg1	structures					1273:1282	site-specific O-glycan structures	1250:1282	site-specific O-glycan structures	1250:1282	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	31	theme	O-glycopeptide	1224:1237	arg1	methods					1298:1304	experimental methods	1285:1304	experimental methods	1285:1304	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	5	32	theme	site-specific	608:620	arg1	O-glycans					622:630	11,633 site-specific O-glycans	601:630	11,633 site-specific O-glycans mapping to 2133 O-glycoproteins	601:662	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	8	33	theme	designed	938:945	arg1	submission					1039:1048	data submission	1034:1048	data submission	1034:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	33	theme	designed	938:945	arg1	modules					965:971	four specially designed and user-friendly modules	923:971	four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission	923:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	33	theme	designed	938:945	arg1	analysis					986:993	statistical analysis	974:993	statistical analysis	974:993	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	33	theme	designed	938:945	arg1	search					1005:1010	database search	996:1010	database search	996:1010	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	33	theme	designed	938:945	arg1	prediction					1018:1027	site prediction	1013:1027	site prediction	1013:1027	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	5	34	gly	O-glycoprotein	687:700	arg1	it					669:670	it	669:670	it	669:670	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	5	34	gly	O-glycoprotein	687:700	arg1	O-glycoprotein					687:700	the largest O-glycoprotein	675:700	the largest O-glycoprotein repository thus far	675:720	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	1	35	theme	Numerous	108:115	arg1	studies					117:123	Numerous studies	108:123	Numerous studies on cancers, biopharmaceuticals, and clinical trials	108:175	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	9	36	theme	O-glycoprotein-related	1133:1154	arg1	information					1156:1166	various O-glycoprotein-related information	1125:1166	various O-glycoprotein-related information	1125:1166	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	1	37	theme	precise	213:219	arg1	analysis					221:228	necessitated comprehensive and precise analysis	182:228	necessitated comprehensive and precise analysis of protein O-glycosylation	182:255	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	11	38	dep	https	1523:1527	arg1	//www.oglyp.org/download.php					1529:1556	//www.oglyp.org/download.php	1529:1556	https://www.oglyp.org/download.php	1523:1556	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	6	39	theme	prediction	792:801	arg1	tool					803:806	an O-glycosylation site prediction tool	768:806	an O-glycosylation site prediction tool	768:806	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	9	40	theme	experimental	1285:1296	arg1	sequences					1239:1247	O-glycopeptide sequences	1224:1247	O-glycopeptide sequences	1224:1247	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	40	theme	experimental	1285:1296	arg1	methods					1298:1304	experimental methods	1285:1304	experimental methods	1285:1304	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	4	41	from	sources	548:554	arg1	collection					499:508	a collection	497:508	a collection of O-glycoprotein data from different sources	497:554	It was constructed with a collection of O-glycoprotein data from different sources.
33581334	4	41	from	sources	548:554	arg1	data					528:531	O-glycoprotein data	513:531	O-glycoprotein data from different sources	513:554	It was constructed with a collection of O-glycoprotein data from different sources.
33581334	8	42	theme	user-friendly	951:963	arg1	submission					1039:1048	data submission	1034:1048	data submission	1034:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	42	theme	user-friendly	951:963	arg1	modules					965:971	four specially designed and user-friendly modules	923:971	four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission	923:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	42	theme	user-friendly	951:963	arg1	analysis					986:993	statistical analysis	974:993	statistical analysis	974:993	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	42	theme	user-friendly	951:963	arg1	search					1005:1010	database search	996:1010	database search	996:1010	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	42	theme	user-friendly	951:963	arg1	prediction					1018:1027	site prediction	1013:1027	site prediction	1013:1027	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	9	43	theme	various	1125:1131	arg1	information					1156:1166	various O-glycoprotein-related information	1125:1166	various O-glycoprotein-related information	1125:1166	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	5	44	gly	O-glycosylation	575:589	arg2	sites					591:595	9354 O-glycosylation sites	570:595	9354 O-glycosylation sites	570:595	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	5	44	gly	O-glycosylation	575:589	arg2	9354					570:573	9354	570:573	9354	570:573	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	0	45	from	Studies	80:86	arg1	O-glycosylation					91:105	O-glycosylation	91:105	O-glycosylation	91:105	OGP: A Repository of Experimentally Characterized O-glycoproteins to Facilitate Studies on O-glycosylation.
33581334	9	46	theme	OGP	1072:1074	arg1	repository					1076:1085	OGP repository	1072:1085	OGP repository	1072:1085	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	47	theme	accession	1185:1193	arg1	Nos.					1195:1198	protein accession Nos.	1177:1198	protein accession Nos.	1177:1198	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	1	48	theme	protein	233:239	arg1	O-glycosylation					241:255	protein O-glycosylation	233:255	protein O-glycosylation	233:255	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	0	49	theme	O-glycoproteins	50:64	arg1	Repository					7:16	A Repository	5:16	A Repository of Experimentally Characterized O-glycoproteins to Facilitate Studies on O-glycosylation	5:105	OGP: A Repository of Experimentally Characterized O-glycoproteins to Facilitate Studies on O-glycosylation.
33581334	4	50	theme	different	538:546	arg1	sources					548:554	different sources	538:554	different sources	538:554	It was constructed with a collection of O-glycoprotein data from different sources.
33581334	1	51	contain	have	177:180	arg2	analysis					221:228	necessitated comprehensive and precise analysis	182:228	necessitated comprehensive and precise analysis of protein O-glycosylation	182:255	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	1	51	contain	have	177:180	arg1	studies					117:123	Numerous studies	108:123	Numerous studies on cancers, biopharmaceuticals, and clinical trials	108:175	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	10	52	theme	related	1448:1454	arg1	studies					1456:1462	related studies	1448:1462	related studies	1448:1462	O-glycosylation data mining can be performed efficiently on this website, which will greatly facilitate related studies.
33581334	2	53	theme	O-glycoprotein	360:373	arg1	data					375:378	emerging O-glycoprotein data	351:378	emerging O-glycoprotein data	351:378	However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data.
33581334	0	54	theme	Characterized	36:48	arg1	O-glycoproteins					50:64	Experimentally Characterized O-glycoproteins	21:64	Experimentally Characterized O-glycoproteins	21:64	OGP: A Repository of Experimentally Characterized O-glycoproteins to Facilitate Studies on O-glycosylation.
33581334	2	55	gly	O-glycoprotein	360:373	arg1	O-glycoprotein					360:373	emerging O-glycoprotein data	351:378	emerging O-glycoprotein data	351:378	However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data.
33581334	9	56	theme	potential	1311:1319	arg1	sites					1337:1341	potential O-glycosylation sites	1311:1341	potential O-glycosylation sites	1311:1341	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	6	57	gly	O-glycosylation	745:759	arg2	sites					761:765	the recorded O-glycosylation sites	732:765	the recorded O-glycosylation sites	732:765	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	5	58	theme	O-glycosylation	575:589	arg1	sites					591:595	9354 O-glycosylation sites	570:595	9354 O-glycosylation sites	570:595	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	2	59	theme	emerging	351:358	arg1	data					375:378	emerging O-glycoprotein data	351:378	emerging O-glycoprotein data	351:378	However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data.
33581334	9	60	theme	first	1055:1059	arg1	version					1061:1067	The first version	1051:1067	The first version of OGP repository	1051:1085	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	11	61	from	website	1514:1520	arg1	accessible					1494:1503	accessible	1494:1503	accessible	1494:1503	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	11	61	from	website	1514:1520	arg1	database					1482:1489	the database	1478:1489	the database	1478:1489	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	2	62	theme	updated	279:285	arg1	databases					302:310	updated and convenient databases	279:310	updated and convenient databases	279:310	However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data.
33581334	0	63	dep	Repository	7:16	arg1	OGP					0:2	OGP	0:2	OGP	0:2	OGP: A Repository of Experimentally Characterized O-glycoproteins to Facilitate Studies on O-glycosylation.
33581334	6	64	theme	site	787:790	arg1	tool					803:806	an O-glycosylation site prediction tool	768:806	an O-glycosylation site prediction tool	768:806	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	1	65	from	studies	117:123	arg1	biopharmaceuticals					137:154	biopharmaceuticals	137:154	biopharmaceuticals	137:154	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	1	65	from	studies	117:123	arg1	cancers					128:134	cancers	128:134	cancers	128:134	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	1	65	from	studies	117:123	arg1	trials					170:175	clinical trials	161:175	clinical trials	161:175	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	1	66	theme	O-glycosylation	241:255	arg1	analysis					221:228	necessitated comprehensive and precise analysis	182:228	necessitated comprehensive and precise analysis of protein O-glycosylation	182:255	Numerous studies on cancers, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation.
33581334	8	67	theme	statistical	974:984	arg1	modules					965:971	four specially designed and user-friendly modules	923:971	four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission	923:1048	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	8	67	theme	statistical	974:984	arg1	analysis					986:993	statistical analysis	974:993	statistical analysis	974:993	The website comprises four specially designed and user-friendly modules: statistical analysis, database search, site prediction, and data submission.
33581334	11	68	from	accessible	1494:1503	arg1	addition					1468:1475	addition	1468:1475	addition	1468:1475	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	6	69	theme	O-glycosylation	771:785	arg1	tool					803:806	an O-glycosylation site prediction tool	768:806	an O-glycosylation site prediction tool	768:806	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	2	70	theme	reference	338:346	arg1	storage					323:329	the storage	319:329	the storage of and reference to emerging O-glycoprotein data	319:378	However, the lack of updated and convenient databases deters the storage of and reference to emerging O-glycoprotein data.
33581334	6	71	gly	O-glycosylation	771:785	arg2	tool					803:806	an O-glycosylation site prediction tool	768:806	an O-glycosylation site prediction tool	768:806	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	6	71	gly	O-glycosylation	771:785	arg2	site					787:790	an O-glycosylation site prediction tool	768:806	an O-glycosylation site prediction tool	768:806	Based on the recorded O-glycosylation sites, an O-glycosylation site prediction tool was developed.
33581334	11	72	from	addition	1468:1475	arg1	accessible					1494:1503	accessible	1494:1503	accessible	1494:1503	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	11	72	from	addition	1468:1475	arg1	database					1482:1489	the database	1478:1489	the database	1478:1489	In addition, the database is accessible from OGP website (https://www.oglyp.org/download.php).
33581334	7	73	dep	available	865:873	arg1	https					876:880	https	876:880	https://www.oglyp.org/	876:897	Moreover, an OGP-based website is already available (https://www.oglyp.org/).
33581334	7	73	dep	available	865:873	arg1	website					846:852	an OGP-based website	833:852	an OGP-based website	833:852	Moreover, an OGP-based website is already available (https://www.oglyp.org/).
33581334	7	73	dep	available	865:873	arg1	available					865:873	available	865:873	available	865:873	Moreover, an OGP-based website is already available (https://www.oglyp.org/).
33581334	9	74	theme	O-glycosylation	1321:1335	arg1	sites					1337:1341	potential O-glycosylation sites	1311:1341	potential O-glycosylation sites	1311:1341	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	5	75	gly	O-glycoproteins	648:662	arg1	O-glycoproteins					648:662	2133 O-glycoproteins	643:662	2133 O-glycoproteins	643:662	OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far.
33581334	3	76	theme	O-glycoprotein	407:420	arg1	repository					422:431	an O-glycoprotein repository	404:431	an O-glycoprotein repository named OGP	404:441	To resolve this issue, an O-glycoprotein repository named OGP was established in this work.
33581334	4	77	theme	O-glycoprotein	513:526	arg1	data					528:531	O-glycoprotein data	513:531	O-glycoprotein data from different sources	513:554	It was constructed with a collection of O-glycoprotein data from different sources.
33581334	0	78	gly	O-glycoproteins	50:64	arg1	O-glycoproteins					50:64	Experimentally Characterized O-glycoproteins	21:64	Experimentally Characterized O-glycoproteins	21:64	OGP: A Repository of Experimentally Characterized O-glycoproteins to Facilitate Studies on O-glycosylation.
33581334	9	79	theme	O-glycosylation	1201:1215	arg1	sites					1217:1221	O-glycosylation sites	1201:1221	O-glycosylation sites	1201:1221	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	80	theme	repository	1076:1085	arg1	version					1061:1067	The first version	1051:1067	The first version of OGP repository	1051:1085	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	80	theme	repository	1076:1085	arg1	repository					1076:1085	OGP repository	1072:1085	OGP repository	1072:1085	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
33581334	9	80	theme	repository	1076:1085	arg1	website					1095:1101	the website	1091:1101	the website	1091:1101	The first version of OGP repository and the website allow users to obtain various O-glycoprotein-related information, such as protein accession Nos., O-glycosylation sites, O-glycopeptide sequences, site-specific O-glycan structures, experimental methods, and potential O-glycosylation sites.
34132802	6	0	dep	G	781:781	arg1	analysis					798:805	N-glycan analysis	789:805	immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	766:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	5	1	theme	large-scale	670:680	arg1	glycoprofiling					682:695	large-scale glycoprofiling	670:695	large-scale glycoprofiling	670:695	However, there is a growing need for highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling.
34132802	10	2	theme	large	1708:1712	arg1	number					1714:1719	a large number	1706:1719	a large number of samples in a high-throughput manner over a longer period of time	1706:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	9	3	theme	glycan	1459:1464	arg1	peaks					1466:1470	low abundance glycan peaks	1445:1470	low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome	1445:1578	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	6	4	theme	RapiFluor-MS	828:839	arg1	Kit					850:852	the GlycoWorks RapiFluor-MS N-Glycan Kit	813:852	the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	813:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	10	5	theme	high-throughput	1737:1751	arg1	manner					1753:1758	a high-throughput manner	1735:1758	a high-throughput manner over a longer period of time	1735:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	8	6	theme	abundant	1254:1261	arg1	peaks					1263:1267	the most abundant peaks	1245:1267	the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all	1245:1341	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	2	7	from	changes	343:349	arg1	glycosylation					354:366	glycosylation	354:366	glycosylation	354:366	Abnormal glycosylation is associated with various diseases, and some of the changes in glycosylation are detectable even before symptom development.
34132802	8	8	theme	detected	1316:1323	arg1	all					1339:1341	the detected IgG N-glycome all	1312:1341	the detected IgG N-glycome all	1312:1341	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	9	9	theme	abundance	1449:1457	arg1	peaks					1466:1470	low abundance glycan peaks	1445:1470	low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome	1445:1578	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	9	10	theme	individual	1481:1490	arg1	area					1506:1509	the individual relative peak area	1477:1509	the individual relative peak area below 1%	1477:1518	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	8	11	theme	N-glycome	1329:1337	arg1	all					1339:1341	the detected IgG N-glycome all	1312:1341	the detected IgG N-glycome all	1312:1341	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	10	12	theme	tested	1609:1614	arg1	method					1616:1621	the tested method	1605:1621	the tested method	1605:1621	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	10	12	theme	tested	1609:1614	arg1	robust					1631:1636	robust	1631:1636	robust	1631:1636	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	10	13	theme	longer	1767:1772	arg1	period					1774:1779	a longer period	1765:1779	a longer period of time	1765:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	9	14	theme	peak	1501:1504	arg1	area					1506:1509	the individual relative peak area	1477:1509	the individual relative peak area below 1%	1477:1518	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	7	15	theme	chromatographic	1120:1134	arg1	columns					1136:1142	chromatographic columns	1120:1142	chromatographic columns	1120:1142	The data was collected over a 5-month period using multiple UHPLC systems and chromatographic columns.
34132802	7	16	theme	5-month	1072:1078	arg1	period					1080:1085	a 5-month period	1070:1085	a 5-month period using multiple UHPLC systems and chromatographic columns	1070:1142	The data was collected over a 5-month period using multiple UHPLC systems and chromatographic columns.
34132802	6	17	theme	plasma	988:993	arg1	technical					958:966	technical	958:966	technical	958:966	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	7	18	theme	multiple	1093:1100	arg1	systems					1108:1114	multiple UHPLC systems	1093:1114	multiple UHPLC systems	1093:1114	The data was collected over a 5-month period using multiple UHPLC systems and chromatographic columns.
34132802	2	19	theme	Abnormal	267:274	arg1	glycosylation					276:288	Abnormal glycosylation	267:288	Abnormal glycosylation	267:288	Abnormal glycosylation is associated with various diseases, and some of the changes in glycosylation are detectable even before symptom development.
34132802	10	20	from	manner	1753:1758	arg1	number					1714:1719	a large number	1706:1719	a large number of samples in a high-throughput manner over a longer period of time	1706:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	0	21	theme	profiling	69:77	arg1	repeatability					15:27	repeatability	15:27	repeatability	15:27	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	0	21	theme	profiling	69:77	arg1	Robustness					0:9	Robustness	0:9	Robustness	0:9	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	0	22	from	repeatability	15:27	arg1	study					119:123	a long-term high-throughput glycomic study	82:123	a long-term high-throughput glycomic study	82:123	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	1	23	theme	carbohydrate	171:182	arg1	moiety					184:189	a carbohydrate moiety	169:189	a carbohydrate moiety	169:189	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	0	24	from	Robustness	0:9	arg1	study					119:123	a long-term high-throughput glycomic study	82:123	a long-term high-throughput glycomic study	82:123	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	0	25	theme	high-throughput	94:108	arg1	study					119:123	a long-term high-throughput glycomic study	82:123	a long-term high-throughput glycomic study	82:123	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	9	26	theme	detected	1557:1564	arg1	N-glycome					1570:1578	the detected IgG N-glycome	1553:1578	the detected IgG N-glycome	1553:1578	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	8	27	from	quantification	1177:1190	arg1	chromatograms					1204:1216	acquired chromatograms	1195:1216	acquired chromatograms	1195:1216	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	9	28	theme	N-glycome	1570:1578	arg1	N-glycome					1570:1578	the detected IgG N-glycome	1553:1578	the detected IgG N-glycome	1553:1578	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	9	28	theme	N-glycome	1570:1578	arg1	%					1548:1548	<2%	1546:1548	<2% of the detected IgG N-glycome	1546:1578	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	2	29	theme	symptom	395:401	arg1	development					403:413	symptom development	395:413	symptom development	395:413	Abnormal glycosylation is associated with various diseases, and some of the changes in glycosylation are detectable even before symptom development.
34132802	10	30	theme	IgG	1681:1683	arg1	analysis					1694:1701	the IgG N-glycan analysis	1677:1701	the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time	1677:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	9	31	theme	highest	1398:1404	arg1	CVs					1406:1408	The highest CVs	1394:1408	The highest CVs ranging from 16 to 29%	1394:1431	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	3	32	theme	new	460:462	arg1	candidates					474:483	compelling new biomarker candidates	449:483	compelling new biomarker candidates	449:483	As such, glycans have emerged as compelling new biomarker candidates.
34132802	0	33	theme	GlycoWorks	32:41	arg1	profiling					69:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	8	34	theme	IgG	1164:1166	arg1	quantification					1177:1190	relative IgG N-glycan quantification	1155:1190	relative IgG N-glycan quantification in acquired chromatograms	1155:1216	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	6	35	theme	liquid	913:918	arg1	HILIC-UHPLC					936:946	HILIC-UHPLC	936:946	HILIC-UHPLC	936:946	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	35	theme	liquid	913:918	arg1	chromatography					920:933	hydrophilic interaction ultra-high-performance liquid chromatography	866:933	hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	866:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	4	36	theme	small-scale	531:541	arg1	analyses					550:557	small-scale glycan analyses	531:557	small-scale glycan analyses	531:557	A wide range of analytical methods exist for small-scale glycan analyses.
34132802	0	37	theme	IgG	56:58	arg1	profiling					69:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	6	38	theme	interaction	878:888	arg1	HILIC-UHPLC					936:946	HILIC-UHPLC	936:946	HILIC-UHPLC	936:946	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	38	theme	interaction	878:888	arg1	chromatography					920:933	hydrophilic interaction ultra-high-performance liquid chromatography	866:933	hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	866:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	39	theme	G	781:781	arg1	repeatability					749:761	repeatability	749:761	repeatability	749:761	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	39	theme	G	781:781	arg1	robustness					734:743	robustness	734:743	robustness	734:743	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	8	40	theme	acquired	1195:1202	arg1	chromatograms					1204:1216	acquired chromatograms	1195:1216	acquired chromatograms	1195:1216	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	10	41	theme	samples	1724:1730	arg1	number					1714:1719	a large number	1706:1719	a large number of samples in a high-throughput manner over a longer period of time	1706:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	6	42	theme	human	982:986	arg1	plasma					988:993	human plasma	982:993	human plasma randomly distributed across 67 96-well plates	982:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	10	43	theme	number	1714:1719	arg1	analysis					1694:1701	the IgG N-glycan analysis	1677:1701	the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time	1677:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	1	44	theme	protein	258:264	arg1	function					242:249	function	242:249	function	242:249	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	1	44	theme	protein	258:264	arg1	structure					228:236	structure	228:236	structure	228:236	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	4	45	theme	analytical	502:511	arg1	methods					513:519	analytical methods	502:519	analytical methods	502:519	A wide range of analytical methods exist for small-scale glycan analyses.
34132802	6	46	dep	technical	958:966	arg1	replicates					968:977	replicates	968:977	replicates	968:977	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	47	theme	N-Glycan	841:848	arg1	Kit					850:852	the GlycoWorks RapiFluor-MS N-Glycan Kit	813:852	the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	813:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	2	48	theme	various	309:315	arg1	diseases					317:324	various diseases	309:324	various diseases	309:324	Abnormal glycosylation is associated with various diseases, and some of the changes in glycosylation are detectable even before symptom development.
34132802	8	49	contain	had	1343:1345	arg1	peaks					1263:1267	the most abundant peaks	1245:1267	the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all	1245:1341	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	8	49	contain	had	1343:1345	arg2	coefficients					1347:1358	coefficients	1347:1358	coefficients of variation (CVs) lower than 2%	1347:1391	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	1	50	attach	attachment	155:164	arg2	moiety					184:189	a carbohydrate moiety	169:189	a carbohydrate moiety	169:189	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	1	50	attach	attachment	155:164	arg1	backbone					204:211	a protein backbone	194:211	a protein backbone affecting both structure and function of the protein	194:264	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	5	51	theme	high-throughput	628:642	arg1	techniques					644:653	highly robust and reproducible high-throughput techniques	597:653	highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling	597:695	However, there is a growing need for highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling.
34132802	6	52	theme	GlycoWorks	817:826	arg1	Kit					850:852	the GlycoWorks RapiFluor-MS N-Glycan Kit	813:852	the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	813:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	1	53	theme	moiety	184:189	arg1	glycosylation					134:146	Protein glycosylation	126:146	Protein glycosylation	126:146	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	1	53	theme	moiety	184:189	arg1	attachment					155:164	the attachment	151:164	the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein	151:264	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	10	54	from	number	1714:1719	arg1	manner					1753:1758	a high-throughput manner	1735:1758	a high-throughput manner over a longer period of time	1735:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	9	55	theme	relative	1492:1499	arg1	area					1506:1509	the individual relative peak area	1477:1509	the individual relative peak area below 1%	1477:1518	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	10	56	from	samples	1724:1730	arg1	manner					1753:1758	a high-throughput manner	1735:1758	a high-throughput manner over a longer period of time	1735:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	8	57	theme	IgG	1325:1327	arg1	all					1339:1341	the detected IgG N-glycome all	1312:1341	the detected IgG N-glycome all	1312:1341	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	6	58	theme	N-glycan	789:796	arg1	analysis					798:805	N-glycan analysis	789:805	immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	766:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	59	theme	96-well	1026:1032	arg1	plates					1034:1039	67 96-well plates	1023:1039	67 96-well plates	1023:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	8	60	theme	all	1339:1341	arg1	three-fourths					1295:1307	three-fourths	1295:1307	three-fourths of the detected IgG N-glycome all	1295:1341	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	1	61	theme	protein	196:202	arg1	backbone					204:211	a protein backbone	194:211	a protein backbone affecting both structure and function of the protein	194:264	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	9	62	dep	29	1429:1430	arg1	to					1426:1427	to	1426:1427	to	1426:1427	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	7	63	theme	UHPLC	1102:1106	arg1	systems					1108:1114	multiple UHPLC systems	1093:1114	multiple UHPLC systems	1093:1114	The data was collected over a 5-month period using multiple UHPLC systems and chromatographic columns.
34132802	10	64	theme	time	1784:1787	arg1	period					1774:1779	a longer period	1765:1779	a longer period of time	1765:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	1	65	theme	Protein	126:132	arg1	glycosylation					134:146	Protein glycosylation	126:146	Protein glycosylation	126:146	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	1	65	theme	Protein	126:132	arg1	attachment					155:164	the attachment	151:164	the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein	151:264	Protein glycosylation is the attachment of a carbohydrate moiety to a protein backbone affecting both structure and function of the protein.
34132802	8	66	theme	variation	1363:1371	arg1	coefficients					1347:1358	coefficients	1347:1358	coefficients of variation (CVs) lower than 2%	1347:1391	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	4	67	theme	methods	513:519	arg1	range					493:497	A wide range	486:497	A wide range of analytical methods	486:519	A wide range of analytical methods exist for small-scale glycan analyses.
34132802	8	68	theme	lower	1379:1383	arg1	coefficients					1347:1358	coefficients	1347:1358	coefficients of variation (CVs) lower than 2%	1347:1391	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	0	69	theme	long-term	84:92	arg1	study					119:123	a long-term high-throughput glycomic study	82:123	a long-term high-throughput glycomic study	82:123	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	0	70	theme	glycomic	110:117	arg1	study					119:123	a long-term high-throughput glycomic study	82:123	a long-term high-throughput glycomic study	82:123	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	5	71	theme	robust	604:609	arg1	techniques					644:653	highly robust and reproducible high-throughput techniques	597:653	highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling	597:695	However, there is a growing need for highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling.
34132802	4	72	theme	wide	488:491	arg1	range					493:497	A wide range	486:497	A wide range of analytical methods	486:519	A wide range of analytical methods exist for small-scale glycan analyses.
34132802	6	73	theme	robustness	734:743	arg1	evaluation					720:729	the evaluation	716:729	the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	716:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	5	74	theme	reproducible	615:626	arg1	techniques					644:653	highly robust and reproducible high-throughput techniques	597:653	highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling	597:695	However, there is a growing need for highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling.
34132802	9	75	theme	IgG	1566:1568	arg1	N-glycome					1570:1578	the detected IgG N-glycome	1553:1578	the detected IgG N-glycome	1553:1578	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	3	76	theme	compelling	449:458	arg1	candidates					474:483	compelling new biomarker candidates	449:483	compelling new biomarker candidates	449:483	As such, glycans have emerged as compelling new biomarker candidates.
34132802	5	77	theme	growing	580:586	arg1	need					588:591	a growing need	578:591	a growing need for highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling	578:695	However, there is a growing need for highly robust and reproducible high-throughput techniques that allow for large-scale glycoprofiling.
34132802	8	78	theme	relative	1155:1162	arg1	quantification					1177:1190	relative IgG N-glycan quantification	1155:1190	relative IgG N-glycan quantification in acquired chromatograms	1155:1216	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	0	79	theme	RapiFluor-MS	43:54	arg1	profiling					69:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	8	80	theme	N-glycan	1168:1175	arg1	quantification					1177:1190	relative IgG N-glycan quantification	1155:1190	relative IgG N-glycan quantification in acquired chromatograms	1155:1216	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	4	81	theme	glycan	543:548	arg1	analyses					550:557	small-scale glycan analyses	531:557	small-scale glycan analyses	531:557	A wide range of analytical methods exist for small-scale glycan analyses.
34132802	9	82	with	peaks	1466:1470	arg1	area					1506:1509	the individual relative peak area	1477:1509	the individual relative peak area below 1%	1477:1518	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34132802	3	83	theme	biomarker	464:472	arg1	candidates					474:483	compelling new biomarker candidates	449:483	compelling new biomarker candidates	449:483	As such, glycans have emerged as compelling new biomarker candidates.
34132802	0	84	theme	N-glycan	60:67	arg1	profiling					69:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	GlycoWorks RapiFluor-MS IgG N-glycan profiling	32:77	Robustness and repeatability of GlycoWorks RapiFluor-MS IgG N-glycan profiling in a long-term high-throughput glycomic study.
34132802	6	85	theme	ultra-high-performance	890:911	arg1	HILIC-UHPLC					936:946	HILIC-UHPLC	936:946	HILIC-UHPLC	936:946	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	85	theme	ultra-high-performance	890:911	arg1	chromatography					920:933	hydrophilic interaction ultra-high-performance liquid chromatography	866:933	hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	866:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	86	theme	hydrophilic	866:876	arg1	HILIC-UHPLC					936:946	HILIC-UHPLC	936:946	HILIC-UHPLC	936:946	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	86	theme	hydrophilic	866:876	arg1	chromatography					920:933	hydrophilic interaction ultra-high-performance liquid chromatography	866:933	hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	866:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	87	theme	immunoglobulin	766:779	arg1	IgG					784:786	IgG	784:786	IgG	784:786	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	87	theme	immunoglobulin	766:779	arg1	G					781:781	immunoglobulin G	766:781	immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	766:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	10	88	theme	N-glycan	1685:1692	arg1	analysis					1694:1701	the IgG N-glycan analysis	1677:1701	the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time	1677:1787	These results show that the tested method is very robust and repeatable, making it suitable for the IgG N-glycan analysis of a large number of samples in a high-throughput manner over a longer period of time.
34132802	8	89	theme	data	1219:1222	arg1	analysis					1224:1231	data analysis	1219:1231	data analysis	1219:1231	Following relative IgG N-glycan quantification in acquired chromatograms, data analysis showed that the most abundant peaks that together made up for three-fourths of the detected IgG N-glycome all had coefficients of variation (CVs) lower than 2%.
34132802	6	90	from	technical	958:966	arg1	HILIC-UHPLC					936:946	HILIC-UHPLC	936:946	HILIC-UHPLC	936:946	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	90	from	technical	958:966	arg1	chromatography					920:933	hydrophilic interaction ultra-high-performance liquid chromatography	866:933	hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	866:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	6	91	theme	repeatability	749:761	arg1	evaluation					720:729	the evaluation	716:729	the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates	716:1039	Here, we describe the evaluation of robustness and repeatability of immunoglobulin G (IgG) N-glycan analysis using the GlycoWorks RapiFluor-MS N-Glycan Kit followed by hydrophilic interaction ultra-high-performance liquid chromatography (HILIC-UHPLC) from 335 technical replicates of human plasma randomly distributed across 67 96-well plates.
34132802	9	92	theme	low	1445:1447	arg1	peaks					1466:1470	low abundance glycan peaks	1445:1470	low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome	1445:1578	The highest CVs ranging from 16 to 29% accompanied low abundance glycan peaks with the individual relative peak area below 1% that together made up for <2% of the detected IgG N-glycome.
34110173	5	0	gly	glycopeptide	1120:1131	arg2	glycopeptide					1120:1131	the glycopeptide level	1116:1137	the glycopeptide level	1116:1137	The site-specificity of N-glycans was revealed at the glycopeptide level by pGlyco software using different proteases.
34110173	3	1	theme	modifications	815:827	arg1	analysis					768:775	the qualitative and quantitative analysis	735:775	the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation)	735:869	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	7	2	theme	LC-MS	1275:1279	arg1	analysis					1281:1288	LC-MS analysis	1275:1288	LC-MS analysis of de-N-glycosylated erythropoietin species	1275:1332	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	1	3	theme	structural	172:181	arg1	heterogeneity					183:195	the structural heterogeneity	168:195	the structural heterogeneity of the therapeutic protein glycosylation	168:236	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	4	4	theme	developed	882:890	arg1	scripts					899:905	The newly developed Python scripts	872:905	The newly developed Python scripts	872:905	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	4	5	theme	N-glycan	1048:1055	arg1	species					1057:1063	8 phosphorylated N-glycan species	1031:1063	8 phosphorylated N-glycan species	1031:1063	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	8	6	theme	manufacturing	1636:1648	arg1	processes					1650:1658	the manufacturing processes	1632:1658	the manufacturing processes	1632:1658	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	3	7	gly	glycopeptides	603:615	arg1	erythropoietin					620:633	erythropoietin	620:633	erythropoietin	620:633	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	3	7	gly	glycopeptides	603:615	arg2	glycopeptides					603:615	enriched glycopeptides	594:615	enriched glycopeptides	594:615	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	5	8	theme	glycopeptide	1120:1131	arg1	level					1133:1137	the glycopeptide level	1116:1137	the glycopeptide level	1116:1137	The site-specificity of N-glycans was revealed at the glycopeptide level by pGlyco software using different proteases.
34110173	3	9	theme	different	798:806	arg1	modifications					815:827	different glycan modifications	798:827	different glycan modifications (e.g., phosphorylation and O-acetylation)	798:869	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	7	10	gly	de-N-glycosylated	1293:1309	arg1	species					1326:1332	de-N-glycosylated erythropoietin species	1293:1332	de-N-glycosylated erythropoietin species	1293:1332	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	2	11	theme	epoetin	345:351	arg1	erythropoietin					329:342	first-generation erythropoietin	312:342	first-generation erythropoietin (epoetin beta)	312:357	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	2	11	theme	epoetin	345:351	arg1	beta					353:356	epoetin beta	345:356	epoetin beta	345:356	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	7	12	theme	mass	1384:1387	arg1	shifts					1389:1394	the mass shifts	1380:1394	the mass shifts between non-O-glycosylated and O-glycosylated species	1380:1448	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	6	13	gly	glycopeptide	1242:1253	arg2	glycopeptide					1242:1253	glycopeptide analysis	1242:1262	glycopeptide analysis	1242:1262	In total, 114 N-glycan compositions were identified from glycopeptide analysis.
34110173	6	14	theme	glycopeptide	1242:1253	arg1	analysis					1255:1262	glycopeptide analysis	1242:1262	glycopeptide analysis	1242:1262	In total, 114 N-glycan compositions were identified from glycopeptide analysis.
34110173	2	15	gly	glycosylation	295:307	arg1	erythropoietin					329:342	first-generation erythropoietin	312:342	first-generation erythropoietin (epoetin beta)	312:357	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	2	15	gly	glycosylation	295:307	arg1	beta					353:356	epoetin beta	345:356	epoetin beta	345:356	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	4	16	dep	species	1057:1063	arg1	including					1021:1029	including	1021:1029	including	1021:1029	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	1	17	theme	glycoproteins	132:144	arg1	characterization					100:115	The characterization	96:115	The characterization of therapeutic glycoproteins	96:144	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	4	18	theme	237	964:966	arg1	structures					977:986	237 N-glycan structures	964:986	237 N-glycan structures	964:986	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	4	18	theme	237	964:966	arg1	compositions					950:961	140 N-glycan compositions	937:961	140 N-glycan compositions (237 N-glycan structures)	937:987	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	2	19	theme	erythropoietin	329:342	arg1	glycosylation					295:307	glycosylation	295:307	glycosylation of first-generation erythropoietin (epoetin beta)	295:357	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	1	20	theme	therapeutic	204:214	arg1	glycosylation					224:236	the therapeutic protein glycosylation	200:236	the therapeutic protein glycosylation	200:236	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	2	21	theme	spectrometric	448:460	arg1	methods					462:468	bottom-up mass spectrometric methods	433:468	bottom-up mass spectrometric methods for site-specific N-glycosylation	433:502	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	7	22	theme	de-N-glycosylated	1293:1309	arg1	species					1326:1332	de-N-glycosylated erythropoietin species	1293:1332	de-N-glycosylated erythropoietin species	1293:1332	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	8	23	gly	glycosylation	1520:1532	arg1	glycoprotein					1560:1571	a therapeutic glycoprotein	1546:1571	a therapeutic glycoprotein	1546:1571	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	8	24	theme	therapeutic	1548:1558	arg1	glycoprotein					1560:1571	a therapeutic glycoprotein	1546:1571	a therapeutic glycoprotein	1546:1571	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	2	25	theme	first-generation	312:327	arg1	erythropoietin					329:342	first-generation erythropoietin	312:342	first-generation erythropoietin (epoetin beta)	312:357	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	2	25	theme	first-generation	312:327	arg1	beta					353:356	epoetin beta	345:356	epoetin beta	345:356	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	2	26	theme	mass	443:446	arg1	methods					462:468	bottom-up mass spectrometric methods	433:468	bottom-up mass spectrometric methods for site-specific N-glycosylation	433:502	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	0	27	theme	Integrated	3:12	arg1	Strategy					14:21	An Integrated Strategy	0:21	An Integrated Strategy	0:21	An Integrated Strategy Reveals Complex Glycosylation of Erythropoietin Using Mass Spectrometry.
34110173	3	28	theme	enriched	594:601	arg1	glycopeptides					603:615	enriched glycopeptides	594:615	enriched glycopeptides	594:615	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	7	29	theme	non-O-glycosylated	1404:1421	arg1	species					1442:1448	non-O-glycosylated and O-glycosylated species	1404:1448	non-O-glycosylated and O-glycosylated species	1404:1448	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	7	30	theme	O-glycan	1349:1356	arg1	compositions					1358:1369	two O-glycan compositions	1345:1369	two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species	1345:1448	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	2	31	theme	bottom-up	433:441	arg1	methods					462:468	bottom-up mass spectrometric methods	433:468	bottom-up mass spectrometric methods for site-specific N-glycosylation	433:502	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	7	32	theme	species	1326:1332	arg1	analysis					1281:1288	LC-MS analysis	1275:1288	LC-MS analysis of de-N-glycosylated erythropoietin species	1275:1332	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	4	33	theme	N-glycan	968:975	arg1	structures					977:986	237 N-glycan structures	964:986	237 N-glycan structures	964:986	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	4	33	theme	N-glycan	968:975	arg1	compositions					950:961	140 N-glycan compositions	937:961	140 N-glycan compositions (237 N-glycan structures)	937:987	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	7	34	gly	non-O-glycosylated	1404:1421	arg1	species					1442:1448	non-O-glycosylated and O-glycosylated species	1404:1448	non-O-glycosylated and O-glycosylated species	1404:1448	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	8	35	theme	glycoprotein	1560:1571	arg1	analysis					1534:1541	the in-depth glycosylation analysis	1507:1541	the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes	1507:1658	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	1	36	theme	protein	216:222	arg1	glycosylation					224:236	the therapeutic protein glycosylation	200:236	the therapeutic protein glycosylation	200:236	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	4	37	theme	N-glycan	941:948	arg1	structures					977:986	237 N-glycan structures	964:986	237 N-glycan structures	964:986	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	4	37	theme	N-glycan	941:948	arg1	compositions					950:961	140 N-glycan compositions	937:961	140 N-glycan compositions (237 N-glycan structures)	937:987	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	5	38	theme	N-glycans	1090:1098	arg1	site-specificity					1070:1085	The site-specificity	1066:1085	The site-specificity of N-glycans	1066:1098	The site-specificity of N-glycans was revealed at the glycopeptide level by pGlyco software using different proteases.
34110173	8	39	dep	analysis	1534:1541	arg1	improving					1622:1630	improving	1622:1630	improving the manufacturing processes	1622:1658	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	8	39	dep	analysis	1534:1541	arg1	understand					1576:1585	understand	1576:1585	to understand its pharmacological properties	1573:1616	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	1	40	theme	glycosylation	224:236	arg1	heterogeneity					183:195	the structural heterogeneity	168:195	the structural heterogeneity of the therapeutic protein glycosylation	168:236	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	4	41	from	erythropoietin	994:1007	arg1	structures					977:986	237 N-glycan structures	964:986	237 N-glycan structures	964:986	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	4	41	from	erythropoietin	994:1007	arg1	identification					919:932	the identification	915:932	the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species	915:1063	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	4	41	from	erythropoietin	994:1007	arg1	compositions					950:961	140 N-glycan compositions	937:961	140 N-glycan compositions (237 N-glycan structures)	937:987	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	1	42	gly	glycoproteins	132:144	arg1	glycoproteins					132:144	therapeutic glycoproteins	120:144	therapeutic glycoproteins	120:144	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	3	43	theme	qualitative	739:749	arg1	analysis					768:775	the qualitative and quantitative analysis	735:775	the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation)	735:869	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	1	44	theme	therapeutic	120:130	arg1	glycoproteins					132:144	therapeutic glycoproteins	120:144	therapeutic glycoproteins	120:144	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	2	45	theme	site-specific	474:486	arg1	N-glycosylation					488:502	site-specific N-glycosylation	474:502	site-specific N-glycosylation	474:502	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	7	46	theme	erythropoietin	1311:1324	arg1	species					1326:1332	de-N-glycosylated erythropoietin species	1293:1332	de-N-glycosylated erythropoietin species	1293:1332	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	8	47	gly	glycoprotein	1560:1571	arg1	glycoprotein					1560:1571	a therapeutic glycoprotein	1546:1571	a therapeutic glycoprotein	1546:1571	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	2	48	theme	analytical	271:280	arg1	strategy					282:289	an in-depth analytical strategy	259:289	an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta)	259:357	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	6	49	theme	N-glycan	1199:1206	arg1	compositions					1208:1219	114 N-glycan compositions	1195:1219	114 N-glycan compositions	1195:1219	In total, 114 N-glycan compositions were identified from glycopeptide analysis.
34110173	3	50	gly	de-N-glycosylated	670:686	arg1	erythropoietin					688:701	de-N-glycosylated erythropoietin	670:701	de-N-glycosylated erythropoietin	670:701	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	2	51	theme	O-glycan	530:537	arg1	identification					539:552	O-glycan identification	530:552	O-glycan identification	530:552	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	0	52	theme	Complex	31:37	arg1	Glycosylation					39:51	Complex Glycosylation	31:51	Complex Glycosylation of Erythropoietin Using Mass Spectrometry	31:93	An Integrated Strategy Reveals Complex Glycosylation of Erythropoietin Using Mass Spectrometry.
34110173	2	53	theme	in-depth	262:269	arg1	strategy					282:289	an in-depth analytical strategy	259:289	an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta)	259:357	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	8	54	theme	integrated	1465:1474	arg1	strategy					1476:1483	this integrated strategy	1460:1483	this integrated strategy	1460:1483	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	0	55	theme	Erythropoietin	56:69	arg1	Glycosylation					39:51	Complex Glycosylation	31:51	Complex Glycosylation of Erythropoietin Using Mass Spectrometry	31:93	An Integrated Strategy Reveals Complex Glycosylation of Erythropoietin Using Mass Spectrometry.
34110173	4	56	theme	compositions	950:961	arg1	identification					919:932	the identification	915:932	the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species	915:1063	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	4	57	theme	phosphorylated	1033:1046	arg1	species					1057:1063	8 phosphorylated N-glycan species	1031:1063	8 phosphorylated N-glycan species	1031:1063	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	2	58	theme	spectrometric	387:399	arg1	workflow					401:408	a developed mass spectrometric workflow	370:408	a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification	370:552	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	7	59	gly	O-glycosylated	1427:1440	arg1	species					1442:1448	non-O-glycosylated and O-glycosylated species	1404:1448	non-O-glycosylated and O-glycosylated species	1404:1448	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34110173	3	60	theme	glycan	808:813	arg1	modifications					815:827	different glycan modifications	798:827	different glycan modifications (e.g., phosphorylation and O-acetylation)	798:869	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	8	61	theme	glycosylation	1520:1532	arg1	analysis					1534:1541	the in-depth glycosylation analysis	1507:1541	the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes	1507:1658	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	3	62	theme	de-N-glycosylated	670:686	arg1	erythropoietin					688:701	de-N-glycosylated erythropoietin	670:701	de-N-glycosylated erythropoietin	670:701	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	2	63	theme	mass	382:385	arg1	workflow					401:408	a developed mass spectrometric workflow	370:408	a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification	370:552	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	3	64	dep	phosphorylation	836:850	arg1	e.g.					830:833	e.g.	830:833	e.g.	830:833	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	1	65	gly	heterogeneity	183:195	arg1	glycosylation					224:236	the therapeutic protein glycosylation	200:236	the therapeutic protein glycosylation	200:236	The characterization of therapeutic glycoproteins is challenging due to the structural heterogeneity of the therapeutic protein glycosylation.
34110173	3	66	theme	glycosylation	780:792	arg1	analysis					768:775	the qualitative and quantitative analysis	735:775	the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation)	735:869	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	5	67	theme	different	1164:1172	arg1	proteases					1174:1182	different proteases	1164:1182	different proteases	1164:1182	The site-specificity of N-glycans was revealed at the glycopeptide level by pGlyco software using different proteases.
34110173	2	68	theme	developed	372:380	arg1	workflow					401:408	a developed mass spectrometric workflow	370:408	a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification	370:552	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	8	69	theme	pharmacological	1591:1605	arg1	properties					1607:1616	its pharmacological properties	1587:1616	its pharmacological properties	1587:1616	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	4	70	theme	Python	892:897	arg1	scripts					899:905	The newly developed Python scripts	872:905	The newly developed Python scripts	872:905	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	3	71	theme	quantitative	755:766	arg1	analysis					768:775	the qualitative and quantitative analysis	735:775	the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation)	735:869	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	0	72	gly	Glycosylation	39:51	arg1	Erythropoietin					56:69	Erythropoietin	56:69	Erythropoietin Using Mass Spectrometry	56:93	An Integrated Strategy Reveals Complex Glycosylation of Erythropoietin Using Mass Spectrometry.
34110173	4	73	from	identification	919:932	arg1	erythropoietin					994:1007	erythropoietin	994:1007	erythropoietin	994:1007	The newly developed Python scripts enabled the identification of 140 N-glycan compositions (237 N-glycan structures) from erythropoietin, especially including 8 phosphorylated N-glycan species.
34110173	3	74	theme	Permethylated	555:567	arg1	N-glycans					569:577	Permethylated N-glycans	555:577	Permethylated N-glycans	555:577	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	0	75	theme	Mass	77:80	arg1	Spectrometry					82:93	Mass Spectrometry	77:93	Mass Spectrometry	77:93	An Integrated Strategy Reveals Complex Glycosylation of Erythropoietin Using Mass Spectrometry.
34110173	5	76	theme	pGlyco	1142:1147	arg1	software					1149:1156	pGlyco software	1142:1156	pGlyco software using different proteases	1142:1182	The site-specificity of N-glycans was revealed at the glycopeptide level by pGlyco software using different proteases.
34110173	8	77	theme	in-depth	1511:1518	arg1	analysis					1534:1541	the in-depth glycosylation analysis	1507:1541	the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes	1507:1658	Finally, this integrated strategy was proved to realize the in-depth glycosylation analysis of a therapeutic glycoprotein to understand its pharmacological properties and improving the manufacturing processes.
34110173	2	78	theme	LC-MS	511:515	arg1	approach					517:524	a LC-MS approach	509:524	a LC-MS approach for O-glycan identification	509:552	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	3	79	theme	erythropoietin	620:633	arg1	N-glycans					569:577	Permethylated N-glycans	555:577	Permethylated N-glycans	555:577	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	3	79	theme	erythropoietin	620:633	arg1	glycopeptides					603:615	enriched glycopeptides	594:615	enriched glycopeptides	594:615	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	3	79	theme	erythropoietin	620:633	arg1	peptides					580:587	peptides	580:587	peptides	580:587	Permethylated N-glycans, peptides, and enriched glycopeptides of erythropoietin were analyzed by nanoLC-MS/MS, and de-N-glycosylated erythropoietin was measured by LC-MS, enabling the qualitative and quantitative analysis of glycosylation and different glycan modifications (e.g., phosphorylation and O-acetylation).
34110173	2	80	theme	N-glycan	414:421	arg1	analysis					423:430	N-glycan analysis	414:430	N-glycan analysis	414:430	This study presents an in-depth analytical strategy for glycosylation of first-generation erythropoietin (epoetin beta), including a developed mass spectrometric workflow for N-glycan analysis, bottom-up mass spectrometric methods for site-specific N-glycosylation, and a LC-MS approach for O-glycan identification.
34110173	7	81	theme	O-glycosylated	1427:1440	arg1	species					1442:1448	non-O-glycosylated and O-glycosylated species	1404:1448	non-O-glycosylated and O-glycosylated species	1404:1448	Moreover, LC-MS analysis of de-N-glycosylated erythropoietin species identified two O-glycan compositions based on the mass shifts between non-O-glycosylated and O-glycosylated species.
34774484	4	0	theme	Trop2	606:610	arg1	N-glycosylation					587:601	N-glycosylation	587:601	N-glycosylation of Trop2	587:610	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	5	1	theme	mutant	695:700	arg1	proteins					702:709	The mutant proteins	691:709	The mutant proteins	691:709	The mutant proteins were characterized in transiently transfected HEK293 cells.
34774484	3	2	theme	tumor	525:529	arg1	antigen					531:537	an important tumor antigen	512:537	an important tumor antigen	512:537	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	10	3	theme	higher	1316:1321	arg1	expression					1331:1340	significantly higher surface expression	1302:1340	significantly higher surface expression of N120A and N208A mutants	1302:1367	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	8	4	theme	aberrant	1051:1058	arg1	glycosylation					1060:1072	aberrant glycosylation	1051:1072	aberrant glycosylation	1051:1072	Our earlier reported Trop2 mutant V194A, which shows aberrant glycosylation, also displayed hampered interaction with claudin-7.
34774484	6	5	theme	mediated	881:888	arg1	cleavage					890:897	matriptase mediated cleavage	870:897	matriptase mediated cleavage	870:897	The N-glycosylation mutants did not affect protein expression, stability, dimerization ability and matriptase mediated cleavage.
34774484	9	6	theme	wild	1189:1192	arg1	type					1194:1197	wild type	1189:1197	wild type	1189:1197	To further characterize the mutants, stable clones expressing wild type and mutant Trop2 were generated in OVCAR3 cell line.
34774484	11	7	theme	fibronectin-mediated	1515:1534	arg1	kinase					1556:1561	Focal adhesion kinase	1541:1561	Focal adhesion kinase	1541:1561	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	11	7	theme	fibronectin-mediated	1515:1534	arg1	FAK					1536:1538	fibronectin-mediated FAK	1515:1538	fibronectin-mediated FAK (Focal adhesion kinase) signaling	1515:1572	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	7	8	theme	N208A	919:923	arg1	mutants					925:931	N120A and N208A mutants	909:931	N120A and N208A mutants	909:931	However, N120A and N208A mutants showed decreased interaction with its binding partner claudin-7.
34774484	1	9	theme	I	150:150	arg1	protein					166:172	a type I transmembrane protein	143:172	a type I transmembrane protein post-translationally modified by N-linked glycosylation	143:228	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	1	9	theme	I	150:150	arg1	antigen					122:128	Trophoblast antigen 2	110:130	Trophoblast antigen 2 (Trop2)	110:138	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	6	10	theme	dimerization	845:856	arg1	ability					858:864	dimerization ability	845:864	dimerization ability	845:864	The N-glycosylation mutants did not affect protein expression, stability, dimerization ability and matriptase mediated cleavage.
34774484	7	11	theme	N120A	909:913	arg1	mutants					925:931	N120A and N208A mutants	909:931	N120A and N208A mutants	909:931	However, N120A and N208A mutants showed decreased interaction with its binding partner claudin-7.
34774484	4	12	theme	site-directed	664:676	arg1	mutagenesis					678:688	site-directed mutagenesis	664:688	site-directed mutagenesis	664:688	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	1	13	theme	N-linked	207:214	arg1	glycosylation					216:228	N-linked glycosylation	207:228	N-linked glycosylation	207:228	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	11	14	theme	type	1476:1479	arg1	Trop2					1481:1485	wild type Trop2	1471:1485	wild type Trop2	1471:1485	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	10	15	theme	N120A	1345:1349	arg1	expression					1331:1340	significantly higher surface expression	1302:1340	significantly higher surface expression of N120A and N208A mutants	1302:1367	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	5	16	theme	transfected	745:755	arg1	HEK293 cells					757:768	transiently transfected HEK293 cells	733:768	transiently transfected HEK293 cells	733:768	The mutant proteins were characterized in transiently transfected HEK293 cells.
34774484	11	17	theme	mutant	1595:1600	arg1	expression					1575:1584	expression	1575:1584	expression of N120A mutant	1575:1600	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	13	18	theme	exosomal	1847:1854	arg1	release					1856:1862	exosomal release	1847:1862	exosomal release	1847:1862	This data suggests that site-specific N-glycan addition determines Trop2 surface density, claudin-7 interaction and exosomal release.
34774484	0	19	with	interaction	61:71	arg1	claudin-7					78:86	claudin-7	78:86	claudin-7	78:86	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	0	19	with	interaction	61:71	arg1	release					101:107	exosomal release	92:107	exosomal release	92:107	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	10	20	theme	N208A	1355:1359	arg1	expression					1331:1340	significantly higher surface expression	1302:1340	significantly higher surface expression of N120A and N208A mutants	1302:1367	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	9	21	theme	mutant	1203:1208	arg1	Trop2					1210:1214	mutant Trop2	1203:1214	mutant Trop2	1203:1214	To further characterize the mutants, stable clones expressing wild type and mutant Trop2 were generated in OVCAR3 cell line.
34774484	12	22	theme	exosomal	1658:1665	arg1	release					1667:1673	exosomal release	1658:1673	exosomal release of Trop2	1658:1682	Furthermore, exosomal release of Trop2 was also decreased in N120A and N208A mutants.
34774484	13	23	theme	surface	1804:1810	arg1	density					1812:1818	Trop2 surface density	1798:1818	Trop2 surface density	1798:1818	This data suggests that site-specific N-glycan addition determines Trop2 surface density, claudin-7 interaction and exosomal release.
34774484	3	24	theme	metastatic	441:450	arg1	breast					468:473	metastatic triple-negative breast and urothelial carcinomas	441:499	breast	468:473	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	11	25	theme	adhesion	1547:1554	arg1	kinase					1556:1561	Focal adhesion kinase	1541:1561	Focal adhesion kinase	1541:1561	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	11	25	theme	adhesion	1547:1554	arg1	FAK					1536:1538	fibronectin-mediated FAK	1515:1538	fibronectin-mediated FAK (Focal adhesion kinase) signaling	1515:1572	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	0	26	theme	N-glycosylation	0:14	arg1	status					16:21	N-glycosylation status	0:21	N-glycosylation status of Trop2	0:30	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	3	27	theme	antibody-drug	374:386	arg1	conjugate					388:396	anti-Trop2 antibody-drug conjugate	363:396	anti-Trop2 antibody-drug conjugate	363:396	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	13	28	theme	N-glycan	1769:1776	arg1	addition					1778:1785	site-specific N-glycan addition	1755:1785	site-specific N-glycan addition	1755:1785	This data suggests that site-specific N-glycan addition determines Trop2 surface density, claudin-7 interaction and exosomal release.
34774484	10	29	theme	Trop2	1432:1436	arg1	mutant					1438:1443	V194A Trop2 mutant	1426:1443	V194A Trop2 mutant	1426:1443	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	3	30	theme	urothelial	479:488	arg1	carcinomas					490:499	metastatic triple-negative breast and urothelial carcinomas	441:499	carcinomas	490:499	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	3	31	theme	breast	468:473	arg1	treatment					428:436	the treatment	424:436	the treatment of metastatic triple-negative breast and urothelial carcinomas	424:499	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	8	32	theme	reported	1010:1017	arg1	V194A					1032:1036	Our earlier reported Trop2 mutant V194A	998:1036	Our earlier reported Trop2 mutant V194A	998:1036	Our earlier reported Trop2 mutant V194A, which shows aberrant glycosylation, also displayed hampered interaction with claudin-7.
34774484	0	33	theme	surface	44:50	arg1	interaction					61:71	interaction	61:71	interaction with claudin-7 and exosomal release	61:107	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	0	33	theme	surface	44:50	arg1	density					52:58	its surface density	40:58	its surface density	40:58	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	8	34	theme	mutant	1025:1030	arg1	V194A					1032:1036	Our earlier reported Trop2 mutant V194A	998:1036	Our earlier reported Trop2 mutant V194A	998:1036	Our earlier reported Trop2 mutant V194A, which shows aberrant glycosylation, also displayed hampered interaction with claudin-7.
34774484	6	35	theme	protein	814:820	arg1	expression					822:831	protein expression	814:831	protein expression	814:831	The N-glycosylation mutants did not affect protein expression, stability, dimerization ability and matriptase mediated cleavage.
34774484	2	36	theme	many	328:331	arg1	cancers					344:350	many epithelial cancers	328:350	many epithelial cancers	328:350	It was originally detected in trophoblasts but was later shown to be frequently overexpressed in many epithelial cancers.
34774484	4	37	theme	specific	628:635	arg1	sites					655:659	specific N-glycan addition sites	628:659	specific N-glycan addition sites	628:659	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	10	38	theme	surface	1267:1273	arg1	assay					1289:1293	surface biotinylation assay	1267:1293	surface biotinylation assay	1267:1293	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	7	39	with	interaction	950:960	arg1	claudin-7					987:995	its binding partner claudin-7	967:995	its binding partner claudin-7	967:995	However, N120A and N208A mutants showed decreased interaction with its binding partner claudin-7.
34774484	4	40	theme	addition	646:653	arg1	sites					655:659	specific N-glycan addition sites	628:659	specific N-glycan addition sites	628:659	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	12	41	dep	N120A	1706:1710	arg1	mutants					1722:1728	mutants	1722:1728	mutants	1722:1728	Furthermore, exosomal release of Trop2 was also decreased in N120A and N208A mutants.
34774484	3	42	theme	important	515:523	arg1	antigen					531:537	an important tumor antigen	512:537	an important tumor antigen	512:537	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	7	43	theme	binding	971:977	arg1	claudin-7					987:995	its binding partner claudin-7	967:995	its binding partner claudin-7	967:995	However, N120A and N208A mutants showed decreased interaction with its binding partner claudin-7.
34774484	10	44	theme	surface	1323:1329	arg1	expression					1331:1340	significantly higher surface expression	1302:1340	significantly higher surface expression of N120A and N208A mutants	1302:1367	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	11	45	theme	FAK	1536:1538	arg1	signaling					1564:1572	fibronectin-mediated FAK (Focal adhesion kinase) signaling	1515:1572	fibronectin-mediated FAK (Focal adhesion kinase) signaling	1515:1572	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	7	46	theme	decreased	940:948	arg1	interaction					950:960	decreased interaction	940:960	decreased interaction with its binding partner claudin-7	940:995	However, N120A and N208A mutants showed decreased interaction with its binding partner claudin-7.
34774484	1	47	theme	type	145:148	arg1	protein					166:172	a type I transmembrane protein	143:172	a type I transmembrane protein post-translationally modified by N-linked glycosylation	143:228	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	1	47	theme	type	145:148	arg1	antigen					122:128	Trophoblast antigen 2	110:130	Trophoblast antigen 2 (Trop2)	110:138	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	8	48	theme	hampered	1090:1097	arg1	interaction					1099:1109	hampered interaction	1090:1109	hampered interaction with claudin-7	1090:1124	Our earlier reported Trop2 mutant V194A, which shows aberrant glycosylation, also displayed hampered interaction with claudin-7.
34774484	1	49	theme	transmembrane	152:164	arg1	protein					166:172	a type I transmembrane protein	143:172	a type I transmembrane protein post-translationally modified by N-linked glycosylation	143:228	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	1	49	theme	transmembrane	152:164	arg1	antigen					122:128	Trophoblast antigen 2	110:130	Trophoblast antigen 2 (Trop2)	110:138	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	11	50	dep	cause	1495:1499	arg1	expression					1575:1584	expression	1575:1584	expression of N120A mutant	1575:1600	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	11	51	theme	Trop2	1481:1485	arg1	overexpression					1453:1466	overexpression	1453:1466	overexpression of wild type Trop2	1453:1485	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	11	52	theme	wild	1471:1474	arg1	Trop2					1481:1485	wild type Trop2	1471:1485	wild type Trop2	1471:1485	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	1	53	theme	Trophoblast	110:120	arg1	protein					166:172	a type I transmembrane protein	143:172	a type I transmembrane protein post-translationally modified by N-linked glycosylation	143:228	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	1	53	theme	Trophoblast	110:120	arg1	antigen					122:128	Trophoblast antigen 2	110:130	Trophoblast antigen 2 (Trop2)	110:138	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	1	53	theme	Trophoblast	110:120	arg1	Trop2					133:137	Trop2	133:137	Trop2	133:137	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	4	54	gly	N-glycosylation	587:601	arg1	Trop2					606:610	Trop2	606:610	Trop2	606:610	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	12	55	theme	Trop2	1678:1682	arg1	release					1667:1673	exosomal release	1658:1673	exosomal release of Trop2	1658:1682	Furthermore, exosomal release of Trop2 was also decreased in N120A and N208A mutants.
34774484	9	56	theme	OVCAR3	1234:1239	arg1	line					1246:1249	OVCAR3 cell line	1234:1249	OVCAR3 cell line	1234:1249	To further characterize the mutants, stable clones expressing wild type and mutant Trop2 were generated in OVCAR3 cell line.
34774484	11	57	theme	N120A	1589:1593	arg1	mutant					1595:1600	N120A mutant	1589:1600	N120A mutant	1589:1600	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	11	58	from	change	1505:1510	arg1	signaling					1564:1572	fibronectin-mediated FAK (Focal adhesion kinase) signaling	1515:1572	fibronectin-mediated FAK (Focal adhesion kinase) signaling	1515:1572	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	11	59	theme	FAK	1630:1632	arg1	signaling					1634:1642	FAK signaling	1630:1642	FAK signaling	1630:1642	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	10	60	theme	surface	1377:1383	arg1	localization					1385:1396	surface localization	1377:1396	surface localization	1377:1396	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	8	61	with	interaction	1099:1109	arg1	claudin-7					1116:1124	claudin-7	1116:1124	claudin-7	1116:1124	Our earlier reported Trop2 mutant V194A, which shows aberrant glycosylation, also displayed hampered interaction with claudin-7.
34774484	1	62	link	N-linked	207:214	arg1	glycosylation					216:228	N-linked glycosylation	207:228	N-linked glycosylation	207:228	Trophoblast antigen 2 (Trop2) is a type I transmembrane protein post-translationally modified by N-linked glycosylation.
34774484	0	63	theme	exosomal	92:99	arg1	release					101:107	exosomal release	92:107	exosomal release	92:107	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	3	64	theme	anti-Trop2	363:372	arg1	conjugate					388:396	anti-Trop2 antibody-drug conjugate	363:396	anti-Trop2 antibody-drug conjugate	363:396	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	6	65	theme	N-glycosylation	775:789	arg1	mutants					791:797	The N-glycosylation mutants	771:797	The N-glycosylation mutants	771:797	The N-glycosylation mutants did not affect protein expression, stability, dimerization ability and matriptase mediated cleavage.
34774484	9	66	theme	stable	1164:1169	arg1	clones					1171:1176	stable clones	1164:1176	stable clones expressing wild type and mutant Trop2	1164:1214	To further characterize the mutants, stable clones expressing wild type and mutant Trop2 were generated in OVCAR3 cell line.
34774484	11	67	theme	Focal	1541:1545	arg1	kinase					1556:1561	Focal adhesion kinase	1541:1561	Focal adhesion kinase	1541:1561	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	11	67	theme	Focal	1541:1545	arg1	FAK					1536:1538	fibronectin-mediated FAK	1515:1538	fibronectin-mediated FAK (Focal adhesion kinase) signaling	1515:1572	Though overexpression of wild type Trop2 did not cause any change in fibronectin-mediated FAK (Focal adhesion kinase) signaling; expression of N120A mutant, surprisingly downregulated FAK signaling.
34774484	3	68	theme	triple-negative	452:466	arg1	breast					468:473	metastatic triple-negative breast and urothelial carcinomas	441:499	breast	468:473	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	13	69	theme	claudin-7	1821:1829	arg1	interaction					1831:1841	claudin-7 interaction	1821:1841	claudin-7 interaction	1821:1841	This data suggests that site-specific N-glycan addition determines Trop2 surface density, claudin-7 interaction and exosomal release.
34774484	0	70	theme	Trop2	26:30	arg1	status					16:21	N-glycosylation status	0:21	N-glycosylation status of Trop2	0:30	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	10	71	dep	N120A	1345:1349	arg1	mutants					1361:1367	mutants	1361:1367	mutants	1361:1367	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	4	72	theme	N-glycosylation	587:601	arg1	significance					571:582	the significance	567:582	the significance of N-glycosylation of Trop2	567:610	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	10	73	theme	V194A	1426:1430	arg1	mutant					1438:1443	V194A Trop2 mutant	1426:1443	V194A Trop2 mutant	1426:1443	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	3	74	theme	carcinomas	490:499	arg1	treatment					428:436	the treatment	424:436	the treatment of metastatic triple-negative breast and urothelial carcinomas	424:499	Recently, anti-Trop2 antibody-drug conjugate has been FDA approved for the treatment of metastatic triple-negative breast and urothelial carcinomas, making it an important tumor antigen.
34774484	0	75	gly	N-glycosylation	0:14	arg1	Trop2					26:30	Trop2	26:30	Trop2	26:30	N-glycosylation status of Trop2 impacts its surface density, interaction with claudin-7 and exosomal release.
34774484	4	76	theme	current	544:550	arg1	study					552:556	The current study	540:556	The current study	540:556	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	13	77	theme	Trop2	1798:1802	arg1	density					1812:1818	Trop2 surface density	1798:1818	Trop2 surface density	1798:1818	This data suggests that site-specific N-glycan addition determines Trop2 surface density, claudin-7 interaction and exosomal release.
34774484	2	78	theme	epithelial	333:342	arg1	cancers					344:350	many epithelial cancers	328:350	many epithelial cancers	328:350	It was originally detected in trophoblasts but was later shown to be frequently overexpressed in many epithelial cancers.
34774484	8	79	theme	Trop2	1019:1023	arg1	V194A					1032:1036	Our earlier reported Trop2 mutant V194A	998:1036	Our earlier reported Trop2 mutant V194A	998:1036	Our earlier reported Trop2 mutant V194A, which shows aberrant glycosylation, also displayed hampered interaction with claudin-7.
34774484	4	80	theme	N-glycan	637:644	arg1	sites					655:659	specific N-glycan addition sites	628:659	specific N-glycan addition sites	628:659	The current study explored the significance of N-glycosylation of Trop2 by substituting specific N-glycan addition sites by site-directed mutagenesis.
34774484	13	81	theme	site-specific	1755:1767	arg1	addition					1778:1785	site-specific N-glycan addition	1755:1785	site-specific N-glycan addition	1755:1785	This data suggests that site-specific N-glycan addition determines Trop2 surface density, claudin-7 interaction and exosomal release.
34774484	9	82	theme	cell	1241:1244	arg1	line					1246:1249	OVCAR3 cell line	1234:1249	OVCAR3 cell line	1234:1249	To further characterize the mutants, stable clones expressing wild type and mutant Trop2 were generated in OVCAR3 cell line.
34774484	7	83	theme	partner	979:985	arg1	claudin-7					987:995	its binding partner claudin-7	967:995	its binding partner claudin-7	967:995	However, N120A and N208A mutants showed decreased interaction with its binding partner claudin-7.
34774484	10	84	theme	biotinylation	1275:1287	arg1	assay					1289:1293	surface biotinylation assay	1267:1293	surface biotinylation assay	1267:1293	Interestingly, surface biotinylation assay showed significantly higher surface expression of N120A and N208A mutants whereas surface localization was drastically reduced for V194A Trop2 mutant.
34774484	2	85	located	detected	249:256	arg2	It					231:232	It	231:232	It	231:232	It was originally detected in trophoblasts but was later shown to be frequently overexpressed in many epithelial cancers.
34774484	2	85	located	detected	249:256	arg1	trophoblasts					261:272	trophoblasts	261:272	trophoblasts	261:272	It was originally detected in trophoblasts but was later shown to be frequently overexpressed in many epithelial cancers.
32269229	2	0	from	present	443:449	arg1	regions					458:464	the regions	454:464	the regions of predicted order	454:483	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	4	1	theme	coiled	1104:1109	arg1	structures					1111:1120	coiled structures	1104:1120	coiled structures	1104:1120	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	5	2	theme	flexible	1280:1287	arg1	residues					1289:1296	charged, polar, hydrophobic and flexible residues	1248:1296	charged, polar, hydrophobic and flexible residues	1248:1296	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	2	3	theme	representative	304:317	arg1	dataset					319:325	a representative dataset	302:325	a representative dataset of 500 human N-glycoproteins	302:354	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	5	4	gly	N-glycosites	1191:1202	arg2	N-glycosites					1191:1202	any N-glycosites	1187:1202	any N-glycosites	1187:1202	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	5	5	gly	N-glycosite	1205:1215	arg2	N-glycosite					1205:1215	N-glycosite	1205:1215	N-glycosite	1205:1215	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	2	6	theme	human	334:338	arg1	N-glycoproteins					340:354	500 human N-glycoproteins	330:354	500 human N-glycoproteins	330:354	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	4	7	gly	N-glycosites	931:942	arg2	N-glycosites					931:942	N-glycosites	931:942	N-glycosites	931:942	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	0	8	link	N-linked	31:38	arg1	glycans					40:46	N-linked glycans	31:46	N-linked glycans	31:46	Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins.
32269229	6	9	gly	N-glycosite	1420:1430	arg2	N-glycosite					1420:1430	N-glycosite	1420:1430	N-glycosite	1420:1430	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	7	10	theme	mutual	1752:1757	arg1	exclusion					1767:1775	the mutual spatial exclusion	1748:1775	the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches	1748:1829	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	5	11	theme	control	1142:1148	arg1	stretches					1169:1177	control disordered residue stretches	1142:1177	control disordered residue stretches without any N-glycosites	1142:1202	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	3	12	theme	sequon	643:648	arg1	signature					650:658	the sequon signature	639:658	the sequon signature for conjugation of N-glycans	639:687	When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans.
32269229	1	13	theme	disorder	170:177	arg1	regions					159:165	regions	159:165	regions of disorder	159:177	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32269229	4	14	theme	flexible	1042:1049	arg1	residues					1066:1073	flexible and accessible residues	1042:1073	flexible and accessible residues that are frequently found in coiled structures	1042:1120	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	0	15	from	locales	19:25	arg1	glycoproteins					70:82	human glycoproteins	64:82	human glycoproteins	64:82	Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins.
32269229	4	16	theme	mutual	724:729	arg1	exclusivity					731:741	mutual exclusivity	724:741	mutual exclusivity between disorder and N-glycosites	724:775	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	6	17	theme	phylogenetic	1466:1477	arg1	conservation					1479:1490	greater phylogenetic conservation	1458:1490	greater phylogenetic conservation among amniotes	1458:1505	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	7	18	theme	structural	1665:1674	arg1	compositions					1676:1687	unique primary structural compositions	1650:1687	unique primary structural compositions	1650:1687	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	4	19	theme	amino	1008:1012	arg1	acids					1014:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	20	theme	amino	793:797	arg1	distribution					804:815	amino acid distribution	793:815	amino acid distribution	793:815	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	5	21	theme	residue	1161:1167	arg1	stretches					1169:1177	control disordered residue stretches	1142:1177	control disordered residue stretches without any N-glycosites	1142:1202	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	7	22	theme	unique	1650:1655	arg1	compositions					1676:1687	unique primary structural compositions	1650:1687	unique primary structural compositions	1650:1687	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	4	23	theme	distribution	804:815	arg1	basis					784:788	the basis	780:788	the basis of amino acid distribution	780:815	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	5	24	theme	structures	1408:1417	arg1	part					1387:1390	part	1387:1390	part of coiled and β structures	1387:1417	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	7	25	theme	disordered	1810:1819	arg1	stretches					1821:1829	disordered stretches	1810:1829	disordered stretches	1810:1829	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	2	26	theme	predicted	469:477	arg1	order					479:483	predicted order	469:483	predicted order	469:483	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	2	27	theme	N-glycosites	409:420	arg1	N-glycosites					409:420	N-glycosites	409:420	N-glycosites	409:420	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	2	27	theme	N-glycosites	409:420	arg1	sites					373:377	the sites	369:377	the sites of N-linked glycosylations or N-glycosites	369:420	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	2	27	theme	N-glycosites	409:420	arg1	glycosylations					391:404	N-linked glycosylations	382:404	N-linked glycosylations	382:404	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	1	28	theme	post-translational	93:110	arg1	modifications					120:132	Several post-translational protein modifications	85:132	Several post-translational protein modifications	85:132	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32269229	7	29	theme	neighborhoods	1792:1804	arg1	exclusion					1767:1775	the mutual spatial exclusion	1748:1775	the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches	1748:1829	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	6	30	theme	ordered	1530:1536	arg1	regions					1538:1544	control ordered regions	1522:1544	control ordered regions	1522:1544	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	4	31	theme	accessible	1055:1064	arg1	residues					1066:1073	flexible and accessible residues	1042:1073	flexible and accessible residues that are frequently found in coiled structures	1042:1120	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	32	theme	ordered	845:851	arg1	stretches					861:869	control ordered residue stretches	837:869	control ordered residue stretches without any N-glycosites	837:894	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	0	33	theme	N-linked	31:38	arg1	glycans					40:46	N-linked glycans	31:46	N-linked glycans	31:46	Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins.
32269229	6	34	theme	disordered	1586:1595	arg1	regions					1605:1611	disordered control regions	1586:1611	disordered control regions	1586:1611	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	1	35	theme	binding	236:242	arg1	versatility					244:254	the binding versatility	232:254	the binding versatility of disordered regions	232:276	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32269229	2	36	theme	glycosylations	391:404	arg1	N-glycosites					409:420	N-glycosites	409:420	N-glycosites	409:420	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	2	36	theme	glycosylations	391:404	arg1	sites					373:377	the sites	369:377	the sites of N-linked glycosylations or N-glycosites	369:420	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	2	36	theme	glycosylations	391:404	arg1	glycosylations					391:404	N-linked glycosylations	382:404	N-linked glycosylations	382:404	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	5	37	theme	aromatic	1315:1322	arg1	residues					1356:1363	aromatic, accessible and order-promoting residues	1315:1363	aromatic, accessible and order-promoting residues	1315:1363	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	3	38	theme	ordered	527:533	arg1	regions					535:541	ordered regions	527:541	ordered regions	527:541	When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans.
32269229	1	39	theme	regions	270:276	arg1	versatility					244:254	the binding versatility	232:254	the binding versatility of disordered regions	232:276	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32269229	7	40	gly	N-glycosite	1780:1790	arg2	N-glycosite					1780:1790	N-glycosite	1780:1790	N-glycosite	1780:1790	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	4	41	theme	residue	897:903	arg1	neighborhoods					905:917	residue neighborhoods	897:917	residue neighborhoods surrounding N-glycosites	897:942	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	1	42	theme	biased	184:189	arg1	localization					191:202	the biased localization	180:202	the biased localization	180:202	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32269229	2	43	link	N-linked	382:389	arg1	glycosylations					391:404	N-linked glycosylations	382:404	N-linked glycosylations	382:404	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	2	44	theme	N-glycoproteins	340:354	arg1	dataset					319:325	a representative dataset	302:325	a representative dataset of 500 human N-glycoproteins	302:354	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	7	45	theme	spatial	1759:1765	arg1	exclusion					1767:1775	the mutual spatial exclusion	1748:1775	the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches	1748:1829	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	6	46	theme	N-glycosite	1420:1430	arg1	neighborhoods					1432:1444	N-glycosite neighborhoods	1420:1444	N-glycosite neighborhoods	1420:1444	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	4	47	theme	bulky	966:970	arg1	acids					1014:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	48	gly	N-glycosites	883:894	arg2	N-glycosites					883:894	any N-glycosites	879:894	any N-glycosites	879:894	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	49	theme	hydrophobic	973:983	arg1	acids					1014:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	6	50	theme	greater	1458:1464	arg1	conservation					1479:1490	greater phylogenetic conservation	1458:1490	greater phylogenetic conservation among amniotes	1458:1505	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	5	51	theme	disordered	1150:1159	arg1	stretches					1169:1177	control disordered residue stretches	1142:1177	control disordered residue stretches without any N-glycosites	1142:1202	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	4	52	theme	exclusivity	731:741	arg1	basis					715:719	the basis	711:719	the basis of mutual exclusivity between disorder and N-glycosites	711:775	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	7	53	theme	differential	1693:1704	arg1	propensities					1706:1717	differential propensities	1693:1717	differential propensities	1693:1717	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	0	54	theme	human	64:68	arg1	glycoproteins					70:82	human glycoproteins	64:82	human glycoproteins	64:82	Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins.
32269229	2	55	from	regions	458:464	arg1	present					443:449	present	443:449	present	443:449	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	5	56	theme	accessible	1325:1334	arg1	residues					1356:1363	aromatic, accessible and order-promoting residues	1315:1363	aromatic, accessible and order-promoting residues	1315:1363	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	7	57	theme	primary	1657:1663	arg1	compositions					1676:1687	unique primary structural compositions	1650:1687	unique primary structural compositions	1650:1687	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	5	58	theme	order-promoting	1340:1354	arg1	residues					1356:1363	aromatic, accessible and order-promoting residues	1315:1363	aromatic, accessible and order-promoting residues	1315:1363	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	4	59	gly	N-glycosites	764:775	arg2	N-glycosites					764:775	N-glycosites	764:775	N-glycosites	764:775	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	60	theme	disorder-promoting	989:1006	arg1	acids					1014:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	bulky, hydrophobic and disorder-promoting amino acids	966:1018	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	0	61	from	disorder	52:59	arg1	glycoproteins					70:82	human glycoproteins	64:82	human glycoproteins	64:82	Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins.
32269229	4	62	located	found	1095:1099	arg1	structures					1111:1120	coiled structures	1104:1120	coiled structures	1104:1120	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	62	located	found	1095:1099	arg2	residues					1066:1073	flexible and accessible residues	1042:1073	flexible and accessible residues that are frequently found in coiled structures	1042:1120	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	5	63	theme	β	1406:1406	arg1	structures					1408:1417	coiled and β structures	1395:1417	coiled and β structures	1395:1417	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	0	64	gly	glycoproteins	70:82	arg1	glycoproteins					70:82	human glycoproteins	64:82	human glycoproteins	64:82	Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins.
32269229	4	65	theme	acids	1014:1018	arg1	depletion					953:961	a depletion	951:961	a depletion of bulky, hydrophobic and disorder-promoting amino acids	951:1018	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	65	theme	acids	1014:1018	arg1	enrichment					1027:1036	an enrichment	1024:1036	an enrichment for flexible and accessible residues that are frequently found in coiled structures	1024:1120	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	4	66	theme	acid	799:802	arg1	distribution					804:815	amino acid distribution	793:815	amino acid distribution	793:815	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	0	67	theme	exclusive	9:17	arg1	locales					19:25	Mutually exclusive locales	0:25	Mutually exclusive locales for N-linked glycans	0:46	Mutually exclusive locales for N-linked glycans and disorder in human glycoproteins.
32269229	1	68	theme	Several	85:91	arg1	modifications					120:132	Several post-translational protein modifications	85:132	Several post-translational protein modifications	85:132	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32269229	7	69	theme	stretches	1821:1829	arg1	exclusion					1767:1775	the mutual spatial exclusion	1748:1775	the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches	1748:1829	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	2	70	gly	N-glycosites	409:420	arg2	N-glycosites					409:420	N-glycosites	409:420	N-glycosites	409:420	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	5	71	theme	polar	1257:1261	arg1	residues					1289:1296	charged, polar, hydrophobic and flexible residues	1248:1296	charged, polar, hydrophobic and flexible residues	1248:1296	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	1	72	theme	protein	112:118	arg1	modifications					120:132	Several post-translational protein modifications	85:132	Several post-translational protein modifications	85:132	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32269229	5	73	theme	coiled	1395:1400	arg1	structures					1408:1417	coiled and β structures	1395:1417	coiled and β structures	1395:1417	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	6	74	theme	control	1522:1528	arg1	regions					1538:1544	control ordered regions	1522:1544	control ordered regions	1522:1544	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	5	75	theme	hydrophobic	1264:1274	arg1	residues					1289:1296	charged, polar, hydrophobic and flexible residues	1248:1296	charged, polar, hydrophobic and flexible residues	1248:1296	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	7	76	theme	N-glycosite	1780:1790	arg1	neighborhoods					1792:1804	N-glycosite neighborhoods	1780:1804	N-glycosite neighborhoods	1780:1804	Our results lead us to propose that unique primary structural compositions and differential propensities for evolvability allowed for the mutual spatial exclusion of N-glycosite neighborhoods and disordered stretches.
32269229	4	77	theme	control	837:843	arg1	stretches					861:869	control ordered residue stretches	837:869	control ordered residue stretches without any N-glycosites	837:894	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	2	78	theme	order	479:483	arg1	regions					458:464	the regions	454:464	the regions of predicted order	454:483	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	4	79	theme	residue	853:859	arg1	stretches					861:869	control ordered residue stretches	837:869	control ordered residue stretches without any N-glycosites	837:894	We then investigated the basis of mutual exclusivity between disorder and N-glycosites on the basis of amino acid distribution: when compared with control ordered residue stretches without any N-glycosites, residue neighborhoods surrounding N-glycosites showed a depletion of bulky, hydrophobic and disorder-promoting amino acids and an enrichment for flexible and accessible residues that are frequently found in coiled structures.
32269229	6	80	theme	control	1597:1603	arg1	regions					1605:1611	disordered control regions	1586:1611	disordered control regions	1586:1611	N-glycosite neighborhoods also showed greater phylogenetic conservation among amniotes, compared with control ordered regions, which in turn were more conserved than disordered control regions.
32269229	5	81	theme	charged	1248:1254	arg1	residues					1289:1296	charged, polar, hydrophobic and flexible residues	1248:1296	charged, polar, hydrophobic and flexible residues	1248:1296	When compared with control disordered residue stretches without any N-glycosites, N-glycosite neighborhoods were depleted of charged, polar, hydrophobic and flexible residues and enriched for aromatic, accessible and order-promoting residues with a tendency to be part of coiled and β structures.
32269229	3	82	theme	N-glycans	679:687	arg1	conjugation					664:674	conjugation	664:674	conjugation of N-glycans	664:687	When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans.
32269229	3	83	theme	disordered	505:514	arg1	stretches					516:524	disordered stretches	505:524	disordered stretches	505:524	When compared with disordered stretches, ordered regions were not found to be enriched for asparagines, serines and threonines, residues that constitute the sequon signature for conjugation of N-glycans.
32269229	2	84	gly	N-glycoproteins	340:354	arg1	N-glycoproteins					340:354	500 human N-glycoproteins	330:354	500 human N-glycoproteins	330:354	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	2	85	theme	N-linked	382:389	arg1	glycosylations					391:404	N-linked glycosylations	382:404	N-linked glycosylations	382:404	However, investigating a representative dataset of 500 human N-glycoproteins, we observed the sites of N-linked glycosylations or N-glycosites, to be predominantly present in the regions of predicted order.
32269229	1	86	theme	disordered	259:268	arg1	regions					270:276	disordered regions	259:276	disordered regions	259:276	Several post-translational protein modifications lie predominantly within regions of disorder: the biased localization has been proposed to expand the binding versatility of disordered regions.
32109505	10	0	from	dynamics	1397:1404	arg1	membrane					1471:1478	lipid membrane	1465:1478	lipid membrane	1465:1478	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	0	from	dynamics	1397:1404	arg1	box					1494:1496	solvation box	1484:1496	solvation box	1484:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	1	theme	glycan	1510:1515	arg1	structure					1517:1525	glycan structure	1510:1525	glycan structure	1510:1525	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	11	2	theme	TRPM8	1647:1651	arg1	spectra					1636:1642	Only spectra	1631:1642	Only spectra of TRPM8 with glc1 glycans	1631:1669	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	9	3	theme	glycan	1197:1202	arg1	structures					1204:1213	two glycan structures	1193:1213	two glycan structures with molecular weight close to the experiment	1193:1259	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	11	4	with	agreement	1679:1687	arg1	experiment					1698:1707	the experiment	1694:1707	the experiment	1694:1707	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	1	5	theme	cellular	180:187	arg1	processes					189:197	various cellular processes	172:197	various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration	172:281	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	6	6	theme	glycosylation	765:777	arg1	state					779:783	The glycosylation state	761:783	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent	761:852	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	2	7	from	located	355:361	arg1	cytoplasm					370:378	the cytoplasm	366:378	the cytoplasm	366:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	11	8	theme	structure	1751:1759	arg1	validation					1725:1734	the validation	1721:1734	the validation of glc1 glycan structure	1721:1759	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	2	9	theme	tetrameric	301:310	arg1	protein					312:318	a large tetrameric protein	293:318	a large tetrameric protein with more than 70% of its residues located in the cytoplasm	293:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	2	9	theme	tetrameric	301:310	arg1	TRPM8					284:288	TRPM8	284:288	TRPM8	284:288	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	1	10	theme	Ca2+	212:215	arg1	uptake					217:222	Ca2+ uptake	212:222	Ca2+ uptake	212:222	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	6	11	gly	glycosylation	765:777	arg1	TRPM8					788:792	TRPM8	788:792	TRPM8	788:792	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	3	12	theme	single	413:418	arg1	site					420:423	a single site	411:423	a single site per subunit	411:435	TRPM8 is N-glycosylated, with a single site per subunit.
32109505	5	13	theme	complex	709:715	arg1	glycans					717:723	complex glycans	709:723	complex glycans	709:723	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	10	14	theme	other	1586:1590	arg1	components					1592:1601	other components	1586:1601	other components from the simulation system	1586:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	1	15	theme	TRP	119:121	arg1	superfamily					123:133	the TRP superfamily	115:133	the TRP superfamily of membrane proteins	115:154	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	7	16	theme	THz	1033:1035	arg1	absorption					1037:1046	an increased THz absorption	1020:1046	an increased THz absorption	1020:1046	Results show a clear difference between cells comprising glycosylated and deglycosylated TRPM8, the first presenting an increased THz absorption.
32109505	7	17	dep	glycosylated	960:971	arg1	TRPM8					992:996	TRPM8	992:996	TRPM8	992:996	Results show a clear difference between cells comprising glycosylated and deglycosylated TRPM8, the first presenting an increased THz absorption.
32109505	1	18	theme	proteins	147:154	arg1	superfamily					123:133	the TRP superfamily	115:133	the TRP superfamily of membrane proteins	115:154	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	10	19	from	membrane	1471:1478	arg1	dynamics					1397:1404	the molecular dynamics	1383:1404	the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box	1383:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	5	20	theme	sole	676:679	arg1	site					695:698	the sole glycosylation site	672:698	the sole glycosylation site	672:698	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	11	21	theme	glc1	1739:1742	arg1	structure					1751:1759	glc1 glycan structure	1739:1759	glc1 glycan structure	1739:1759	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	0	22	theme	molecular	78:86	arg1	modelling					88:96	molecular modelling	78:96	molecular modelling	78:96	N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling.
32109505	9	23	theme	sugar	1296:1300	arg1	glc1					1308:1311	glc1	1308:1311	glc1	1308:1311	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	9	23	theme	sugar	1296:1300	arg1	unit					1302:1305	the first sugar unit	1286:1305	the first sugar unit (glc1)	1286:1312	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	4	24	theme	channel	488:494	arg1	N-glycosylation					463:477	the N-glycosylation	459:477	the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells	459:595	This work focuses on the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells.
32109505	10	25	theme	unglycosylated	1409:1422	arg1	dynamics					1397:1404	the molecular dynamics	1383:1404	the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box	1383:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	26	theme	THz	1362:1364	arg1	spectra					1366:1372	THz spectra	1362:1372	THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box	1362:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	27	theme	models	1455:1460	arg1	dynamics					1397:1404	the molecular dynamics	1383:1404	the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box	1383:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	5	28	theme	molecular	732:740	arg1	weight					742:747	a molecular weight	730:747	a molecular weight of 2.5 kDa	730:758	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	8	29	theme	Human	1049:1053	arg1	TRPM8					1055:1059	Human TRPM8	1049:1059	Human TRPM8	1049:1059	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	7	30	theme	clear	918:922	arg1	difference					924:933	a clear difference	916:933	a clear difference between cells comprising glycosylated and deglycosylated TRPM8, the first presenting an increased THz absorption	916:1046	Results show a clear difference between cells comprising glycosylated and deglycosylated TRPM8, the first presenting an increased THz absorption.
32109505	10	31	theme	glycosylated	1436:1447	arg1	models					1455:1460	the two glycosylated TRPM8 models	1428:1460	the two glycosylated TRPM8 models	1428:1460	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	0	32	theme	N-glycosylation	0:14	arg1	state					16:20	N-glycosylation state	0:20	N-glycosylation state of TRPM8 protein	0:37	N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling.
32109505	1	33	theme	TRPM8	99:103	arg1	member					105:110	TRPM8 member	99:110	TRPM8 member of the TRP superfamily of membrane proteins	99:154	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	9	34	dep	modelled	1169:1176	arg1	unbranched					1329:1338	unbranched	1329:1338	unbranched	1329:1338	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	9	34	dep	modelled	1169:1176	arg1	longer					1318:1323	longer	1318:1323	longer	1318:1323	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	9	34	dep	modelled	1169:1176	arg1	branched					1274:1281	branched	1274:1281	branched	1274:1281	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	9	34	dep	modelled	1169:1176	arg1	glc2					1341:1344	glc2	1341:1344	glc2	1341:1344	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	9	34	dep	modelled	1169:1176	arg1	shorter					1262:1268	shorter	1262:1268	shorter	1262:1268	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	5	35	contain	contains	700:707	arg1	site					695:698	the sole glycosylation site	672:698	the sole glycosylation site	672:698	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	5	35	contain	contains	700:707	arg2	glycans					717:723	complex glycans	709:723	complex glycans	709:723	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	10	36	theme	lipid	1465:1469	arg1	membrane					1471:1478	lipid membrane	1465:1478	lipid membrane	1465:1478	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	0	37	theme	protein	31:37	arg1	state					16:20	N-glycosylation state	0:20	N-glycosylation state of TRPM8 protein	0:37	N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling.
32109505	2	38	from	cytoplasm	370:378	arg1	located					355:361	located	355:361	located	355:361	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	6	39	from	state	779:783	arg1	cells					797:801	cells	797:801	cells untreated and treated with a deglycosylating agent	797:852	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	8	40	theme	available	1097:1105	arg1	templates					1083:1091	templates	1083:1091	templates	1083:1091	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	8	40	theme	available	1097:1105	arg1	TRPM8					1107:1111	the available TRPM8	1093:1111	the available TRPM8	1093:1111	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	8	40	theme	available	1097:1105	arg1	channels					1128:1135	other TRPM channels	1117:1135	other TRPM channels	1117:1135	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	1	41	theme	cold	228:231	arg1	sensation					233:241	cold sensation	228:241	cold sensation	228:241	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	10	42	from	system	1623:1628	arg1	components					1592:1601	other components	1586:1601	other components from the simulation system	1586:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	42	from	system	1623:1628	arg1	spectrum					1555:1562	the THz spectrum	1547:1562	the THz spectrum of the channel and of other components from the simulation system	1547:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	8	43	theme	TRPM	1123:1126	arg1	templates					1083:1091	templates	1083:1091	templates	1083:1091	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	8	43	theme	TRPM	1123:1126	arg1	TRPM8					1107:1111	the available TRPM8	1093:1111	the available TRPM8	1093:1111	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	8	43	theme	TRPM	1123:1126	arg1	channels					1128:1135	other TRPM channels	1117:1135	other TRPM channels	1117:1135	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	4	44	theme	cells	591:595	arg1	migration					570:578	migration	570:578	migration	570:578	This work focuses on the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells.
32109505	4	44	theme	cells	591:595	arg1	proliferation					552:564	proliferation	552:564	proliferation	552:564	This work focuses on the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells.
32109505	11	45	theme	Only	1631:1634	arg1	spectra					1636:1642	Only spectra	1631:1642	Only spectra of TRPM8 with glc1 glycans	1631:1669	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	2	46	theme	residues	346:353	arg1	%					337:337	more than 70%	325:337	more than 70% of its residues located in the cytoplasm	325:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	2	46	theme	residues	346:353	arg1	residues					346:353	its residues	342:353	its residues located in the cytoplasm	342:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	10	47	theme	molecular	1387:1395	arg1	dynamics					1397:1404	the molecular dynamics	1383:1404	the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box	1383:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	5	48	theme	deglycosylating	637:651	arg1	agents					653:658	deglycosylating agents	637:658	deglycosylating agents	637:658	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	10	49	theme	spectra	1366:1372	arg1	Simulation					1348:1357	Simulation	1348:1357	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box	1348:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	2	50	theme	large	295:299	arg1	protein					312:318	a large tetrameric protein	293:318	a large tetrameric protein with more than 70% of its residues located in the cytoplasm	293:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	2	50	theme	large	295:299	arg1	TRPM8					284:288	TRPM8	284:288	TRPM8	284:288	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	3	51	with	N-glycosylated	390:403	arg1	site					420:423	a single site	411:423	a single site per subunit	411:435	TRPM8 is N-glycosylated, with a single site per subunit.
32109505	10	52	theme	THz	1551:1553	arg1	spectrum					1555:1562	the THz spectrum	1547:1562	the THz spectrum of the channel and of other components from the simulation system	1547:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	6	53	theme	TRPM8	788:792	arg1	state					779:783	The glycosylation state	761:783	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent	761:852	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	1	54	theme	various	172:178	arg1	processes					189:197	various cellular processes	172:197	various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration	172:281	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	6	55	theme	Terahertz	873:881	arg1	spectroscopy					889:900	Terahertz (THz) spectroscopy	873:900	Terahertz (THz) spectroscopy	873:900	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	10	56	from	box	1494:1496	arg1	dynamics					1397:1404	the molecular dynamics	1383:1404	the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box	1383:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	5	57	theme	experimental	604:615	arg1	data					617:620	experimental data	604:620	experimental data performed with deglycosylating agents	604:658	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	9	58	theme	molecular	1220:1228	arg1	weight					1230:1235	molecular weight	1220:1235	molecular weight close to the experiment	1220:1259	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	5	59	gly	deglycosylating	637:651	arg0	agents					653:658	deglycosylating agents	637:658	deglycosylating agents	637:658	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	10	60	theme	channel	1571:1577	arg1	spectrum					1555:1562	the THz spectrum	1547:1562	the THz spectrum of the channel and of other components from the simulation system	1547:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	5	61	theme	glycosylation	681:693	arg1	site					695:698	the sole glycosylation site	672:698	the sole glycosylation site	672:698	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	4	62	gly	N-glycosylation	463:477	arg1	channel					488:494	TRPM8 channel	482:494	TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells	482:595	This work focuses on the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells.
32109505	9	63	from	unit	1302:1305	arg1	branched					1274:1281	branched	1274:1281	branched	1274:1281	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	8	64	dep	TRPM8	1107:1111	arg1	structures					1137:1146	structures	1137:1146	structures	1137:1146	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	10	65	theme	components	1592:1601	arg1	spectrum					1555:1562	the THz spectrum	1547:1562	the THz spectrum of the channel and of other components from the simulation system	1547:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	5	66	gly	glycosylation	681:693	arg2	site					695:698	the sole glycosylation site	672:698	the sole glycosylation site	672:698	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	7	67	theme	increased	1023:1031	arg1	absorption					1037:1046	an increased THz absorption	1020:1046	an increased THz absorption	1020:1046	Results show a clear difference between cells comprising glycosylated and deglycosylated TRPM8, the first presenting an increased THz absorption.
32109505	1	68	theme	superfamily	123:133	arg1	member					105:110	TRPM8 member	99:110	TRPM8 member of the TRP superfamily of membrane proteins	99:154	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	1	69	theme	membrane	138:145	arg1	proteins					147:154	membrane proteins	138:154	membrane proteins	138:154	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32109505	4	70	theme	TRPM8	482:486	arg1	channel					488:494	TRPM8 channel	482:494	TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells	482:595	This work focuses on the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells.
32109505	5	71	theme	2.5 kDa	752:758	arg1	weight					742:747	a molecular weight	730:747	a molecular weight of 2.5 kDa	730:758	Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa.
32109505	9	72	theme	first	1290:1294	arg1	glc1					1308:1311	glc1	1308:1311	glc1	1308:1311	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	9	72	theme	first	1290:1294	arg1	unit					1302:1305	the first sugar unit	1286:1305	the first sugar unit (glc1)	1286:1312	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	2	73	with	protein	312:318	arg1	%					337:337	more than 70%	325:337	more than 70% of its residues located in the cytoplasm	325:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	2	73	with	protein	312:318	arg1	residues					346:353	its residues	342:353	its residues located in the cytoplasm	342:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	11	74	theme	glycan	1744:1749	arg1	structure					1751:1759	glc1 glycan structure	1739:1759	glc1 glycan structure	1739:1759	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	3	75	gly	N-glycosylated	390:403	arg1	TRPM8					381:385	TRPM8	381:385	TRPM8	381:385	TRPM8 is N-glycosylated, with a single site per subunit.
32109505	10	76	theme	TRPM8	1449:1453	arg1	models					1455:1460	the two glycosylated TRPM8 models	1428:1460	the two glycosylated TRPM8 models	1428:1460	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	77	theme	simulation	1612:1621	arg1	system					1623:1628	the simulation system	1608:1628	the simulation system	1608:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	0	78	theme	TRPM8	25:29	arg1	protein					31:37	TRPM8 protein	25:37	TRPM8 protein	25:37	N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling.
32109505	6	79	dep	cells	797:801	arg1	treated					817:823	treated	817:823	treated with a deglycosylating agent	817:852	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	6	79	dep	cells	797:801	arg1	untreated					803:811	untreated	803:811	untreated	803:811	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	6	80	gly	deglycosylating	832:846	arg0	agent					848:852	a deglycosylating agent	830:852	a deglycosylating agent	830:852	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	0	81	gly	N-glycosylation	0:14	arg1	protein					31:37	TRPM8 protein	25:37	TRPM8 protein	25:37	N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling.
32109505	11	82	theme	glc1	1658:1661	arg1	glycans					1663:1669	glc1 glycans	1658:1669	glc1 glycans	1658:1669	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	0	83	theme	terahertz	51:59	arg1	spectroscopy					61:72	terahertz spectroscopy	51:72	terahertz spectroscopy	51:72	N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling.
32109505	9	84	with	structures	1204:1213	arg1	weight					1230:1235	molecular weight	1220:1235	molecular weight close to the experiment	1220:1259	Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2).
32109505	6	85	theme	deglycosylating	832:846	arg1	agent					848:852	a deglycosylating agent	830:852	a deglycosylating agent	830:852	The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy.
32109505	11	86	with	spectra	1636:1642	arg1	glycans					1663:1669	glc1 glycans	1658:1669	glc1 glycans	1658:1669	Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.
32109505	8	87	theme	other	1117:1121	arg1	templates					1083:1091	templates	1083:1091	templates	1083:1091	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	8	87	theme	other	1117:1121	arg1	TRPM8					1107:1111	the available TRPM8	1093:1111	the available TRPM8	1093:1111	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	8	87	theme	other	1117:1121	arg1	channels					1128:1135	other TRPM channels	1117:1135	other TRPM channels	1117:1135	Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures.
32109505	4	88	theme	tumoral	583:589	arg1	cells					591:595	tumoral cells	583:595	tumoral cells	583:595	This work focuses on the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells.
32109505	10	89	theme	solvation	1484:1492	arg1	box					1494:1496	solvation box	1484:1496	solvation box	1484:1496	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	90	from	spectrum	1555:1562	arg1	system					1623:1628	the simulation system	1608:1628	the simulation system	1608:1628	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	10	91	gly	glycosylated	1436:1447	arg1	models					1455:1460	the two glycosylated TRPM8 models	1428:1460	the two glycosylated TRPM8 models	1428:1460	Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system.
32109505	2	92	theme	located	355:361	arg1	residues					346:353	its residues	342:353	its residues located in the cytoplasm	342:378	TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm.
32109505	1	93	theme	cellular	246:253	arg1	proliferation					255:267	proliferation	255:267	proliferation	255:267	TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration.
32827291	1	0	theme	sugar	334:338	arg1	moieties					262:269	growing sugar moieties	248:269	growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis	248:360	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	4	1	theme	drastic	836:842	arg1	decrease					844:851	drastic decrease	836:851	drastic decrease in the amount of KS proteoglycans	836:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	3	2	theme	greater	485:491	arg1	impact					493:498	greater impact	485:498	greater impact	485:498	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	3	3	attach	presence	571:578	arg2	N-glycans					583:591	N-glycans	583:591	N-glycans	583:591	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	3	3	attach	presence	571:578	arg1	sites					601:605	both sites	596:605	both sites	596:605	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	1	4	theme	growing	248:254	arg1	moieties					262:269	growing sugar moieties	248:269	growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis	248:360	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	4	5	from	decrease	844:851	arg1	O-glycans					935:943	O-glycans	935:943	O-glycans	935:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	5	from	decrease	844:851	arg1	N-					928:929	N-	928:929	N-	928:929	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	5	from	decrease	844:851	arg1	amount					860:865	the amount	856:865	the amount of KS proteoglycans	856:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	5	from	decrease	844:851	arg1	proteoglycans					873:885	KS proteoglycans	870:885	KS proteoglycans	870:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	3	6	theme	active	662:667	arg1	protein					669:675	stable and enzymatically active protein	637:675	stable and enzymatically active protein	637:675	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	1	7	theme	sugar	256:260	arg1	moieties					262:269	growing sugar moieties	248:269	growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis	248:360	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	1	8	theme	lactose	344:350	arg1	synthesis					352:360	lactose synthesis	344:360	lactose synthesis	344:360	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	2	9	gly	glycosylation	405:417	arg2	sites					419:423	two asparagine-linked glycosylation sites	383:423	two asparagine-linked glycosylation sites in B4GalT4	383:434	Herein, we identify two asparagine-linked glycosylation sites in B4GalT4.
32827291	2	9	gly	glycosylation	405:417	arg2	two					383:385	two	383:385	two	383:385	Herein, we identify two asparagine-linked glycosylation sites in B4GalT4.
32827291	4	10	from	changes	917:923	arg1	O-glycans					935:943	O-glycans	935:943	O-glycans	935:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	10	from	changes	917:923	arg1	N-					928:929	N-	928:929	N-	928:929	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	10	from	changes	917:923	arg1	amount					860:865	the amount	856:865	the amount of KS proteoglycans	856:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	10	from	changes	917:923	arg1	proteoglycans					873:885	KS proteoglycans	870:885	KS proteoglycans	870:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	0	11	theme	Golgi	90:94	arg1	localization					96:107	Golgi localization	90:107	Golgi localization	90:107	N-glycosylation of the human β1,4-galactosyltransferase 4 is crucial for its activity and Golgi localization.
32827291	5	12	gly	glycosylated	1077:1088	arg1	B4GalT4					1090:1096	either partially or fully glycosylated B4GalT4	1051:1096	either partially or fully glycosylated B4GalT4	1051:1096	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	4	13	theme	cell	815:818	arg1	lines					820:824	A375 B4GalT4 knock-out cell lines	792:824	A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans	792:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	3	14	theme	site	467:470	arg1	mutation					451:458	mutation	451:458	mutation of one site (Asn220)	451:479	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	4	15	theme	keratan	757:763	arg1	KS					774:775	KS	774:775	KS	774:775	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	15	theme	keratan	757:763	arg1	sulfate					765:771	keratan sulfate	757:771	keratan sulfate (KS)	757:776	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	5	16	from	decrease	962:969	arg1	cells					979:983	A375 cells	974:983	A375 cells deficient in B4GalT4 activity	974:1013	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	1	17	theme	B4GalTs	165:171	arg1	one					152:154	one	152:154	one	152:154	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	1	17	theme	B4GalTs	165:171	arg1	B4GalTs					165:171	seven B4GalTs	159:171	seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis	159:360	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	3	18	contain	had	481:483	arg2	impact					493:498	greater impact	485:498	greater impact	485:498	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	3	18	contain	had	481:483	arg1	mutation					451:458	mutation	451:458	mutation of one site (Asn220)	451:479	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	4	19	theme	knock-out	805:813	arg1	lines					820:824	A375 B4GalT4 knock-out cell lines	792:824	A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans	792:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	20	from	involvement	729:739	arg1	synthesis					744:752	synthesis	744:752	synthesis of keratan sulfate (KS)	744:776	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	3	21	from	sites	601:605	arg1	presence					571:578	presence	571:578	presence	571:578	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	3	21	from	sites	601:605	arg1	localization					554:565	Golgi localization	548:565	Golgi localization	548:565	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	5	22	theme	B4GalT4	1090:1096	arg1	overproduction					1033:1046	overproduction	1033:1046	overproduction of either partially or fully glycosylated B4GalT4	1033:1096	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	1	23	theme	proteins	274:281	arg1	moieties					262:269	growing sugar moieties	248:269	growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis	248:360	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	3	24	theme	Golgi	548:552	arg1	localization					554:565	Golgi localization	548:565	Golgi localization	548:565	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	0	25	theme	human	23:27	arg1	β1,4-galactosyltransferase					29:54	the human β1,4-galactosyltransferase 4	19:56	the human β1,4-galactosyltransferase 4	19:56	N-glycosylation of the human β1,4-galactosyltransferase 4 is crucial for its activity and Golgi localization.
32827291	5	26	theme	KS	959:960	arg1	decrease					962:969	KS decrease	959:969	KS decrease in A375 cells deficient in B4GalT4 activity	959:1013	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	5	27	theme	deficient	985:993	arg1	cells					979:983	A375 cells	974:983	A375 cells deficient in B4GalT4 activity	974:1013	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	5	28	from	deficient	985:993	arg1	activity					1006:1013	B4GalT4 activity	998:1013	B4GalT4 activity	998:1013	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	1	29	theme	CAZy	188:191	arg1	family					213:218	CAZy glycosyltransferase family 7	188:220	CAZy glycosyltransferase family 7	188:220	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	5	30	theme	glycosylated	1077:1088	arg1	B4GalT4					1090:1096	either partially or fully glycosylated B4GalT4	1051:1096	either partially or fully glycosylated B4GalT4	1051:1096	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	4	31	theme	proteoglycans	873:885	arg1	amount					860:865	the amount	856:865	the amount of KS proteoglycans	856:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	31	theme	proteoglycans	873:885	arg1	proteoglycans					873:885	KS proteoglycans	870:885	KS proteoglycans	870:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	4	32	theme	B4GalT4	721:727	arg1	involvement					729:739	B4GalT4 involvement	721:739	B4GalT4 involvement in synthesis of keratan sulfate (KS)	721:776	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	1	33	theme	glycosyltransferase	193:211	arg1	family					213:218	CAZy glycosyltransferase family 7	188:220	CAZy glycosyltransferase family 7	188:220	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	4	34	theme	significant	894:904	arg1	changes					917:923	no significant structural changes	891:923	no significant structural changes in N- and O-glycans	891:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	0	35	gly	N-glycosylation	0:14	arg1	β1,4-galactosyltransferase					29:54	the human β1,4-galactosyltransferase 4	19:56	the human β1,4-galactosyltransferase 4	19:56	N-glycosylation of the human β1,4-galactosyltransferase 4 is crucial for its activity and Golgi localization.
32827291	2	36	theme	asparagine-linked	387:403	arg1	sites					419:423	two asparagine-linked glycosylation sites	383:423	two asparagine-linked glycosylation sites in B4GalT4	383:434	Herein, we identify two asparagine-linked glycosylation sites in B4GalT4.
32827291	0	37	theme	β1,4-galactosyltransferase	29:54	arg1	N-glycosylation					0:14	N-glycosylation	0:14	N-glycosylation of the human β1,4-galactosyltransferase 4	0:56	N-glycosylation of the human β1,4-galactosyltransferase 4 is crucial for its activity and Golgi localization.
32827291	2	38	link	asparagine-linked	387:403	arg1	sites					419:423	two asparagine-linked glycosylation sites	383:423	two asparagine-linked glycosylation sites in B4GalT4	383:434	Herein, we identify two asparagine-linked glycosylation sites in B4GalT4.
32827291	5	39	theme	A375	974:977	arg1	cells					979:983	A375 cells	974:983	A375 cells deficient in B4GalT4 activity	974:1013	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	2	40	theme	glycosylation	405:417	arg1	sites					419:423	two asparagine-linked glycosylation sites	383:423	two asparagine-linked glycosylation sites in B4GalT4	383:434	Herein, we identify two asparagine-linked glycosylation sites in B4GalT4.
32827291	4	41	theme	B4GalT4	797:803	arg1	lines					820:824	A375 B4GalT4 knock-out cell lines	792:824	A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans	792:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	3	42	theme	protein	669:675	arg1	production					623:632	production	623:632	production of stable and enzymatically active protein	623:675	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	3	42	theme	protein	669:675	arg1	secretion					685:693	its secretion	681:693	its secretion	681:693	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	5	43	theme	N-glycan-depleted	1111:1127	arg1	version					1137:1143	N-glycan-depleted B4GalT4 version	1111:1143	N-glycan-depleted B4GalT4 version	1111:1143	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	4	44	theme	A375	792:795	arg1	lines					820:824	A375 B4GalT4 knock-out cell lines	792:824	A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans	792:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	5	45	theme	B4GalT4	1129:1135	arg1	version					1137:1143	N-glycan-depleted B4GalT4 version	1111:1143	N-glycan-depleted B4GalT4 version	1111:1143	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	4	46	theme	KS	870:871	arg1	proteoglycans					873:885	KS proteoglycans	870:885	KS proteoglycans	870:885	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	5	47	theme	B4GalT4	998:1004	arg1	activity					1006:1013	B4GalT4 activity	998:1013	B4GalT4 activity	998:1013	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	4	48	theme	sulfate	765:771	arg1	synthesis					744:752	synthesis	744:752	synthesis of keratan sulfate (KS)	744:776	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32827291	2	49	from	sites	419:423	arg1	B4GalT4					428:434	B4GalT4	428:434	B4GalT4	428:434	Herein, we identify two asparagine-linked glycosylation sites in B4GalT4.
32827291	5	50	from	activity	1006:1013	arg1	deficient					985:993	deficient	985:993	deficient	985:993	We show that KS decrease in A375 cells deficient in B4GalT4 activity can be rescued by overproduction of either partially or fully glycosylated B4GalT4 but not with N-glycan-depleted B4GalT4 version.
32827291	3	51	theme	stable	637:642	arg1	protein					669:675	stable and enzymatically active protein	637:675	stable and enzymatically active protein	637:675	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	3	52	theme	N-glycans	583:591	arg1	presence					571:578	presence	571:578	presence	571:578	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	3	52	theme	N-glycans	583:591	arg1	localization					554:565	Golgi localization	548:565	Golgi localization	548:565	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	1	53	theme	single	327:332	arg1	sugar					334:338	single sugar	327:338	proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis	274:360	β1,4-galactosyltransferase 4 (B4GalT4) is one of seven B4GalTs that belong to CAZy glycosyltransferase family 7 and transfer galactose to growing sugar moieties of proteins, glycolipids, glycosaminoglycans as well as single sugar for lactose synthesis.
32827291	3	54	theme	enzymatic	503:511	arg1	activity					513:520	enzymatic activity	503:520	enzymatic activity	503:520	We found that mutation of one site (Asn220) had greater impact on enzymatic activity while another (Asn335) on Golgi localization and presence of N-glycans at both sites is required for production of stable and enzymatically active protein and its secretion.
32827291	4	55	theme	structural	906:915	arg1	changes					917:923	no significant structural changes	891:923	no significant structural changes in N- and O-glycans	891:943	Additionally, we confirm B4GalT4 involvement in synthesis of keratan sulfate (KS) by generating A375 B4GalT4 knock-out cell lines that show drastic decrease in the amount of KS proteoglycans and no significant structural changes in N- and O-glycans.
32168410	8	0	theme	knock	1038:1042	arg1	mice					1048:1051	FXIII-B knock out mice	1030:1051	FXIII-B knock out mice	1030:1051	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	4	1	theme	Asparagine-linked	574:590	arg1	carbohydrates					592:604	Asparagine-linked carbohydrates	574:604	METHODS Asparagine-linked carbohydrates	566:604	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	3	2	theme	dimeric	497:503	arg1	structure					505:513	the dimeric structure	493:513	the dimeric structure of FXIII-B and its clearance from the circulation	493:563	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	5	3	theme	N-linked	676:683	arg1	oligosaccharides					685:700	The released N-linked oligosaccharides	663:700	The released N-linked oligosaccharides	663:700	The released N-linked oligosaccharides were fluorophore labeled and analyzed by capillary electrophoresis.
32168410	3	4	from	structure	505:513	arg1	circulation					553:563	the circulation	549:563	the circulation	549:563	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	3	5	theme	clearance	534:542	arg1	structure					505:513	the dimeric structure	493:513	the dimeric structure of FXIII-B and its clearance from the circulation	493:563	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	7	6	theme	gel	935:937	arg1	filtration					939:948	gel filtration	935:948	gel filtration	935:948	The structure of deglycosylated FXIII-B was investigated by gel filtration.
32168410	12	7	theme	FXIII-B	1516:1522	arg1	mice					1534:1537	FXIII-B knock out mice	1516:1537	FXIII-B knock out mice	1516:1537	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	1	8	gly	glycoprotein	189:200	arg1	subunits					130:137	The protective/inhibitory B subunits	102:137	The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B)	102:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	8	gly	glycoprotein	189:200	arg1	glycoprotein					189:200	a ~80 kDa glycoprotein	179:200	a ~80 kDa glycoprotein containing two N-glycosylation sites	179:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	6	9	theme	based	857:861	arg1	sequencing					863:872	based sequencing	857:872	based sequencing	857:872	Structural identification utilized glycan database search and exoglycosidase digestion based sequencing.
32168410	12	10	theme	out	1530:1532	arg1	mice					1534:1537	FXIII-B knock out mice	1516:1537	FXIII-B knock out mice	1516:1537	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	13	11	attach	attached	1591:1598	arg1	FXIII-B					1603:1609	FXIII-B	1603:1609	FXIII-B	1603:1609	CONCLUSION Characterization of the glycan moieties attached to FXIII-B is reported for the first time.
32168410	13	11	attach	attached	1591:1598	arg2	moieties					1582:1589	the glycan moieties	1571:1589	the glycan moieties attached to FXIII-B	1571:1609	CONCLUSION Characterization of the glycan moieties attached to FXIII-B is reported for the first time.
32168410	6	12	theme	exoglycosidase	832:845	arg1	digestion					847:855	exoglycosidase digestion	832:855	exoglycosidase digestion	832:855	Structural identification utilized glycan database search and exoglycosidase digestion based sequencing.
32168410	7	13	theme	FXIII-B	907:913	arg1	structure					879:887	The structure	875:887	The structure of deglycosylated FXIII-B	875:913	The structure of deglycosylated FXIII-B was investigated by gel filtration.
32168410	1	14	theme	~80 kDa	181:187	arg1	subunits					130:137	The protective/inhibitory B subunits	102:137	The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B)	102:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	14	theme	~80 kDa	181:187	arg1	glycoprotein					189:200	a ~80 kDa glycoprotein	179:200	a ~80 kDa glycoprotein containing two N-glycosylation sites	179:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	4	15	theme	PNGase	643:648	arg1	digestion					652:660	PNGase F digestion	643:660	PNGase F digestion	643:660	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	9	16	theme	PNGase	1062:1067	arg1	F					1069:1069	RESULTS PNGase F	1054:1069	RESULTS PNGase F	1054:1069	RESULTS PNGase F completely removed N-glycans from the denatured protein.
32168410	5	17	theme	capillary	743:751	arg1	electrophoresis					753:767	capillary electrophoresis	743:767	capillary electrophoresis	743:767	The released N-linked oligosaccharides were fluorophore labeled and analyzed by capillary electrophoresis.
32168410	1	18	theme	N-glycosylation	217:231	arg1	sites					233:237	two N-glycosylation sites	213:237	two N-glycosylation sites	213:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	10	19	from	concentration	1222:1234	arg1	digestion					1191:1199	repeated digestion	1182:1199	repeated digestion at elevated PNGase F concentration	1182:1234	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	1	20	theme	coagulation	142:152	arg1	XIII					161:164	coagulation factor XIII	142:164	coagulation factor XIII (FXIII-B)	142:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	20	theme	coagulation	142:152	arg1	FXIII-B					167:173	FXIII-B	167:173	FXIII-B	167:173	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	3	21	attach	linked	373:378	arg2	structures					362:371	the glycan structures	351:371	the glycan structures linked to FXIII-B	351:389	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	3	21	attach	linked	373:378	arg1	FXIII-B					383:389	FXIII-B	383:389	FXIII-B	383:389	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	12	22	theme	dimeric	1432:1438	arg1	structure					1440:1448	the native dimeric structure	1421:1448	the native dimeric structure of FXIII-B	1421:1459	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	14	23	theme	protein	1682:1688	arg1	deglycosylation					1652:1666	Complete deglycosylation	1643:1666	Complete deglycosylation of the native protein	1643:1688	Complete deglycosylation of the native protein was achieved by a deglycosylation workflow.
32168410	1	24	theme	XIII	161:164	arg1	subunits					130:137	The protective/inhibitory B subunits	102:137	The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B)	102:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	24	theme	XIII	161:164	arg1	glycoprotein					189:200	a ~80 kDa glycoprotein	179:200	a ~80 kDa glycoprotein containing two N-glycosylation sites	179:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	11	25	theme	sialic	1377:1382	arg1	acid					1384:1387	at least one sialic acid	1364:1387	at least one sialic acid	1364:1387	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	0	26	theme	functional	67:76	arg1	consequence					78:88	its functional consequence	63:88	its functional consequence	63:88	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	10	27	theme	protein	1158:1164	arg1	Deglycosylation					1128:1142	Deglycosylation	1128:1142	Deglycosylation of the native protein	1128:1164	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	3	28	theme	glycan	355:360	arg1	structures					362:371	the glycan structures	351:371	the glycan structures linked to FXIII-B	351:389	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	1	29	theme	protective/inhibitory	106:126	arg1	subunits					130:137	The protective/inhibitory B subunits	102:137	The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B)	102:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	29	theme	protective/inhibitory	106:126	arg1	glycoprotein					189:200	a ~80 kDa glycoprotein	179:200	a ~80 kDa glycoprotein containing two N-glycosylation sites	179:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	13	30	theme	glycan	1575:1580	arg1	moieties					1582:1589	the glycan moieties	1571:1589	the glycan moieties attached to FXIII-B	1571:1609	CONCLUSION Characterization of the glycan moieties attached to FXIII-B is reported for the first time.
32168410	3	31	from	circulation	553:563	arg1	FXIII-B					518:524	FXIII-B	518:524	FXIII-B	518:524	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	3	31	from	circulation	553:563	arg1	clearance					534:542	its clearance	530:542	its clearance from the circulation	530:563	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	3	31	from	circulation	553:563	arg1	structure					505:513	the dimeric structure	493:513	the dimeric structure of FXIII-B and its clearance from the circulation	493:563	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	10	32	theme	repeated	1182:1189	arg1	digestion					1191:1199	repeated digestion	1182:1199	repeated digestion at elevated PNGase F concentration	1182:1234	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	0	33	theme	blood	19:23	arg1	XIII					44:47	blood coagulation factor XIII	19:47	blood coagulation factor XIII subunit B	19:57	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	10	34	theme	PNGase	1213:1218	arg1	concentration					1222:1234	elevated PNGase F concentration	1204:1234	elevated PNGase F concentration	1204:1234	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	11	35	theme	individual	1289:1298	arg1	structures					1300:1309	nine individual structures	1284:1309	nine individual structures; three were fucosylated and each structure contained at least one sialic acid	1284:1387	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	8	36	theme	FXIII-B	994:1000	arg1	clearance					955:963	The clearance	951:963	The clearance of deglycosylated and native FXIII-B from plasma	951:1012	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	1	37	theme	factor	154:159	arg1	XIII					161:164	coagulation factor XIII	142:164	coagulation factor XIII (FXIII-B)	142:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	37	theme	factor	154:159	arg1	FXIII-B					167:173	FXIII-B	167:173	FXIII-B	167:173	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	13	38	theme	moieties	1582:1589	arg1	Characterization					1551:1566	CONCLUSION Characterization	1540:1566	CONCLUSION Characterization of the glycan moieties attached to FXIII-B	1540:1609	CONCLUSION Characterization of the glycan moieties attached to FXIII-B is reported for the first time.
32168410	0	39	theme	factor	37:42	arg1	XIII					44:47	blood coagulation factor XIII	19:47	blood coagulation factor XIII subunit B	19:57	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	8	40	gly	deglycosylated	968:981	arg1	FXIII-B					994:1000	deglycosylated and native FXIII-B	968:1000	deglycosylated and native FXIII-B	968:1000	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	6	41	theme	database	812:819	arg1	search					821:826	glycan database search	805:826	glycan database search	805:826	Structural identification utilized glycan database search and exoglycosidase digestion based sequencing.
32168410	0	42	theme	subunit	49:55	arg1	B					57:57	blood coagulation factor XIII subunit B	19:57	blood coagulation factor XIII subunit B	19:57	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	15	43	theme	FXIII-B	1786:1792	arg1	formation					1800:1808	FXIII-B dimer formation	1786:1808	FXIII-B dimer formation	1786:1808	The associated glycan structure is not required for FXIII-B dimer formation, but it very likely prolongs the half-life of FXIII-B in the plasma.
32168410	4	44	link	Asparagine-linked	574:590	arg1	carbohydrates					592:604	Asparagine-linked carbohydrates	574:604	METHODS Asparagine-linked carbohydrates	566:604	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	11	45	theme	N-glycan	1247:1254	arg1	profile					1256:1262	The total N-glycan profile	1237:1262	The total N-glycan profile of FXIII-B	1237:1273	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	8	46	theme	FXIII-B	1030:1036	arg1	mice					1048:1051	FXIII-B knock out mice	1030:1051	FXIII-B knock out mice	1030:1051	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	11	47	contain	contained	1354:1362	arg1	structure					1344:1352	each structure	1339:1352	each structure	1339:1352	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	11	47	contain	contained	1354:1362	arg2	acid					1384:1387	at least one sialic acid	1364:1387	at least one sialic acid	1364:1387	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	6	48	theme	Structural	770:779	arg1	identification					781:794	Structural identification	770:794	Structural identification	770:794	Structural identification utilized glycan database search and exoglycosidase digestion based sequencing.
32168410	8	49	theme	out	1044:1046	arg1	mice					1048:1051	FXIII-B knock out mice	1030:1051	FXIII-B knock out mice	1030:1051	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	4	50	theme	human	625:629	arg1	FXIIII-B					631:638	human FXIIII-B	625:638	human FXIIII-B	625:638	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	11	51	dep	structures	1300:1309	arg1	fucosylated					1323:1333	fucosylated	1323:1333	were fucosylated	1318:1333	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	11	51	dep	structures	1300:1309	arg1	contained					1354:1362	contained	1354:1362	contained at least one sialic acid	1354:1387	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	11	52	gly	fucosylated	1323:1333	arg1	three					1312:1316	three	1312:1316	three	1312:1316	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	11	52	gly	fucosylated	1323:1333	arg1	structures					1300:1309	nine individual structures	1284:1309	nine individual structures; three were fucosylated and each structure contained at least one sialic acid	1284:1387	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	6	53	dep	search	821:826	arg1	sequencing					863:872	based sequencing	857:872	based sequencing	857:872	Structural identification utilized glycan database search and exoglycosidase digestion based sequencing.
32168410	5	54	theme	released	667:674	arg1	oligosaccharides					685:700	The released N-linked oligosaccharides	663:700	The released N-linked oligosaccharides	663:700	The released N-linked oligosaccharides were fluorophore labeled and analyzed by capillary electrophoresis.
32168410	2	55	theme	glycans	293:299	arg1	role					281:284	the functional role	266:284	the functional role of the glycans on FXIII-B	266:310	Neither the structure nor the functional role of the glycans on FXIII-B has been explored.
32168410	12	56	theme	knock	1524:1528	arg1	mice					1534:1537	FXIII-B knock out mice	1516:1537	FXIII-B knock out mice	1516:1537	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	3	57	theme	FXIII-B	518:524	arg1	structure					505:513	the dimeric structure	493:513	the dimeric structure of FXIII-B and its clearance from the circulation	493:563	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	12	58	theme	mice	1534:1537	arg1	circulation					1501:1511	the circulation	1497:1511	the circulation of FXIII-B knock out mice	1497:1537	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	1	59	gly	N-glycosylation	217:231	arg2	sites					233:237	two N-glycosylation sites	213:237	two N-glycosylation sites	213:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	59	gly	N-glycosylation	217:231	arg2	two					213:215	two	213:215	two	213:215	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	15	60	theme	dimer	1794:1798	arg1	formation					1800:1808	FXIII-B dimer formation	1786:1808	FXIII-B dimer formation	1786:1808	The associated glycan structure is not required for FXIII-B dimer formation, but it very likely prolongs the half-life of FXIII-B in the plasma.
32168410	15	61	from	half-life	1843:1851	arg1	plasma					1871:1876	the plasma	1867:1876	the plasma	1867:1876	The associated glycan structure is not required for FXIII-B dimer formation, but it very likely prolongs the half-life of FXIII-B in the plasma.
32168410	9	62	theme	RESULTS	1054:1060	arg1	F					1069:1069	RESULTS PNGase F	1054:1069	RESULTS PNGase F	1054:1069	RESULTS PNGase F completely removed N-glycans from the denatured protein.
32168410	15	63	theme	glycan	1749:1754	arg1	structure					1756:1764	The associated glycan structure	1734:1764	The associated glycan structure	1734:1764	The associated glycan structure is not required for FXIII-B dimer formation, but it very likely prolongs the half-life of FXIII-B in the plasma.
32168410	4	64	attach	released	611:618	arg2	METHODS					566:572	METHODS Asparagine-linked carbohydrates	566:604	METHODS Asparagine-linked carbohydrates	566:604	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	4	64	attach	released	611:618	arg1	FXIIII-B					631:638	human FXIIII-B	625:638	human FXIIII-B	625:638	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	7	65	theme	deglycosylated	892:905	arg1	FXIII-B					907:913	deglycosylated FXIII-B	892:913	deglycosylated FXIII-B	892:913	The structure of deglycosylated FXIII-B was investigated by gel filtration.
32168410	14	66	theme	deglycosylation	1708:1722	arg1	workflow					1724:1731	a deglycosylation workflow	1706:1731	a deglycosylation workflow	1706:1731	Complete deglycosylation of the native protein was achieved by a deglycosylation workflow.
32168410	4	67	theme	F	650:650	arg1	digestion					652:660	PNGase F digestion	643:660	PNGase F digestion	643:660	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	4	68	dep	METHODS	566:572	arg1	carbohydrates					592:604	Asparagine-linked carbohydrates	574:604	METHODS Asparagine-linked carbohydrates	566:604	METHODS Asparagine-linked carbohydrates were released from human FXIIII-B by PNGase F digestion.
32168410	1	69	theme	B	128:128	arg1	subunits					130:137	The protective/inhibitory B subunits	102:137	The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B)	102:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	69	theme	B	128:128	arg1	glycoprotein					189:200	a ~80 kDa glycoprotein	179:200	a ~80 kDa glycoprotein containing two N-glycosylation sites	179:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	14	70	gly	deglycosylation	1652:1666	arg1	protein					1682:1688	the native protein	1671:1688	the native protein	1671:1688	Complete deglycosylation of the native protein was achieved by a deglycosylation workflow.
32168410	12	71	theme	FXIII-B	1453:1459	arg1	structure					1440:1448	the native dimeric structure	1421:1448	the native dimeric structure of FXIII-B	1421:1459	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	15	72	theme	FXIII-B	1856:1862	arg1	half-life					1843:1851	the half-life	1839:1851	the half-life of FXIII-B in the plasma	1839:1876	The associated glycan structure is not required for FXIII-B dimer formation, but it very likely prolongs the half-life of FXIII-B in the plasma.
32168410	2	73	theme	functional	270:279	arg1	role					281:284	the functional role	266:284	the functional role of the glycans on FXIII-B	266:310	Neither the structure nor the functional role of the glycans on FXIII-B has been explored.
32168410	2	74	from	role	281:284	arg1	FXIII-B					304:310	FXIII-B	304:310	FXIII-B	304:310	Neither the structure nor the functional role of the glycans on FXIII-B has been explored.
32168410	9	75	theme	denatured	1109:1117	arg1	protein					1119:1125	the denatured protein	1105:1125	the denatured protein	1105:1125	RESULTS PNGase F completely removed N-glycans from the denatured protein.
32168410	13	76	theme	first	1631:1635	arg1	time					1637:1640	the first time	1627:1640	the first time	1627:1640	CONCLUSION Characterization of the glycan moieties attached to FXIII-B is reported for the first time.
32168410	6	77	used	utilized	796:803	arg2	identification					781:794	Structural identification	770:794	Structural identification	770:794	Structural identification utilized glycan database search and exoglycosidase digestion based sequencing.
32168410	12	78	theme	native	1425:1430	arg1	structure					1440:1448	the native dimeric structure	1421:1448	the native dimeric structure of FXIII-B	1421:1459	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	14	79	theme	native	1675:1680	arg1	protein					1682:1688	the native protein	1671:1688	the native protein	1671:1688	Complete deglycosylation of the native protein was achieved by a deglycosylation workflow.
32168410	7	80	gly	deglycosylated	892:905	arg1	FXIII-B					907:913	deglycosylated FXIII-B	892:913	deglycosylated FXIII-B	892:913	The structure of deglycosylated FXIII-B was investigated by gel filtration.
32168410	1	81	dep	BACKGROUND	91:100	arg1	subunits					130:137	The protective/inhibitory B subunits	102:137	The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B)	102:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	81	dep	BACKGROUND	91:100	arg1	glycoprotein					189:200	a ~80 kDa glycoprotein	179:200	a ~80 kDa glycoprotein containing two N-glycosylation sites	179:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	10	82	theme	native	1151:1156	arg1	protein					1158:1164	the native protein	1147:1164	the native protein	1147:1164	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	11	83	theme	FXIII-B	1267:1273	arg1	profile					1256:1262	The total N-glycan profile	1237:1262	The total N-glycan profile of FXIII-B	1237:1273	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	5	84	dep	labeled	719:725	arg1	fluorophore					707:717	fluorophore	707:717	fluorophore	707:717	The released N-linked oligosaccharides were fluorophore labeled and analyzed by capillary electrophoresis.
32168410	14	85	theme	Complete	1643:1650	arg1	deglycosylation					1652:1666	Complete deglycosylation	1643:1666	Complete deglycosylation of the native protein	1643:1688	Complete deglycosylation of the native protein was achieved by a deglycosylation workflow.
32168410	12	86	from	circulation	1501:1511	arg1	clearance					1482:1490	its clearance	1478:1490	its clearance from the circulation of FXIII-B knock out mice	1478:1537	Deglycosylation did not change the native dimeric structure of FXIII-B, but accelerated its clearance from the circulation of FXIII-B knock out mice.
32168410	3	87	theme	native	435:440	arg1	protein					442:448	the native protein	431:448	the native protein	431:448	OBJECTIVE To reveal the glycan structures linked to FXIII-B, to design a method for deglycosylating the native protein, to find out if deglycosylation influences the dimeric structure of FXIII-B and its clearance from the circulation.
32168410	8	88	from	plasma	1007:1012	arg1	clearance					955:963	The clearance	951:963	The clearance of deglycosylated and native FXIII-B from plasma	951:1012	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	10	89	gly	Deglycosylation	1128:1142	arg1	protein					1158:1164	the native protein	1147:1164	the native protein	1147:1164	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	0	90	theme	coagulation	25:35	arg1	XIII					44:47	blood coagulation factor XIII	19:47	blood coagulation factor XIII subunit B	19:57	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	10	91	theme	F	1220:1220	arg1	concentration					1222:1234	elevated PNGase F concentration	1204:1234	elevated PNGase F concentration	1204:1234	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	8	92	theme	deglycosylated	968:981	arg1	FXIII-B					994:1000	deglycosylated and native FXIII-B	968:1000	deglycosylated and native FXIII-B	968:1000	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	15	93	theme	associated	1738:1747	arg1	structure					1756:1764	The associated glycan structure	1734:1764	The associated glycan structure	1734:1764	The associated glycan structure is not required for FXIII-B dimer formation, but it very likely prolongs the half-life of FXIII-B in the plasma.
32168410	5	94	link	N-linked	676:683	arg1	oligosaccharides					685:700	The released N-linked oligosaccharides	663:700	The released N-linked oligosaccharides	663:700	The released N-linked oligosaccharides were fluorophore labeled and analyzed by capillary electrophoresis.
32168410	0	95	theme	XIII	44:47	arg1	B					57:57	blood coagulation factor XIII subunit B	19:57	blood coagulation factor XIII subunit B	19:57	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	10	96	theme	elevated	1204:1211	arg1	concentration					1222:1234	elevated PNGase F concentration	1204:1234	elevated PNGase F concentration	1204:1234	Deglycosylation of the native protein was achieved by repeated digestion at elevated PNGase F concentration.
32168410	0	97	gly	N-glycosylation	0:14	arg1	B					57:57	blood coagulation factor XIII subunit B	19:57	blood coagulation factor XIII subunit B	19:57	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	8	98	theme	native	987:992	arg1	FXIII-B					994:1000	deglycosylated and native FXIII-B	968:1000	deglycosylated and native FXIII-B	968:1000	The clearance of deglycosylated and native FXIII-B from plasma was compared in FXIII-B knock out mice.
32168410	0	99	theme	B	57:57	arg1	N-glycosylation					0:14	N-glycosylation	0:14	N-glycosylation of blood coagulation factor XIII subunit B	0:57	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	0	99	theme	B	57:57	arg1	consequence					78:88	its functional consequence	63:88	its functional consequence	63:88	N-glycosylation of blood coagulation factor XIII subunit B and its functional consequence.
32168410	6	100	theme	glycan	805:810	arg1	search					821:826	glycan database search	805:826	glycan database search	805:826	Structural identification utilized glycan database search and exoglycosidase digestion based sequencing.
32168410	13	101	theme	CONCLUSION	1540:1549	arg1	Characterization					1551:1566	CONCLUSION Characterization	1540:1566	CONCLUSION Characterization of the glycan moieties attached to FXIII-B	1540:1609	CONCLUSION Characterization of the glycan moieties attached to FXIII-B is reported for the first time.
32168410	11	102	theme	total	1241:1245	arg1	profile					1256:1262	The total N-glycan profile	1237:1262	The total N-glycan profile of FXIII-B	1237:1273	The total N-glycan profile of FXIII-B featured nine individual structures; three were fucosylated and each structure contained at least one sialic acid.
32168410	1	103	contain	containing	202:211	arg2	sites					233:237	two N-glycosylation sites	213:237	two N-glycosylation sites	213:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	103	contain	containing	202:211	arg1	subunits					130:137	The protective/inhibitory B subunits	102:137	The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B)	102:174	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
32168410	1	103	contain	containing	202:211	arg1	glycoprotein					189:200	a ~80 kDa glycoprotein	179:200	a ~80 kDa glycoprotein containing two N-glycosylation sites	179:237	BACKGROUND The protective/inhibitory B subunits of coagulation factor XIII (FXIII-B) is a ~80 kDa glycoprotein containing two N-glycosylation sites.
31913636	3	0	theme	PNGase	709:714	arg1	F					716:716	PNGase F	709:716	PNGase F	709:716	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	4	1	theme	other	872:876	arg1	glycoprotein					939:950	the envelope glycoprotein	926:950	the envelope glycoprotein (Env) from HIV	926:965	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	4	1	theme	other	872:876	arg1	antigens					906:913	other viral glycoproteins/vaccine antigens	872:913	other viral glycoproteins/vaccine antigens	872:913	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	2	2	theme	vaccine	362:368	arg1	HA					423:424	HA	423:424	HA	423:424	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	2	2	theme	vaccine	362:368	arg1	antigen					370:376	the principal influenza vaccine antigen and major viral spike protein hemagglutinin	338:420	antigen	370:376	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	0	3	theme	Vaccine	85:91	arg1	Antigens					93:100	Vaccine Antigens	85:100	Vaccine Antigens	85:100	Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.
31913636	7	4	theme	therapeutic	1522:1532	arg1	glycoproteins					1534:1546	re-engineering therapeutic glycoproteins	1507:1546	re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy	1507:1668	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	7	4	theme	therapeutic	1522:1532	arg1	HA					1566:1567	influenza HA	1556:1567	influenza HA	1556:1567	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	7	4	theme	therapeutic	1522:1532	arg1	Env					1576:1578	HIV Env	1572:1578	HIV Env	1572:1578	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	5	5	theme	PNGase	1074:1079	arg1	activity					1083:1090	PNGase F activity	1074:1090	PNGase F activity	1074:1090	Covalent N-glycan reattachment was nonenzymatic as it occurred in the presence of metal ions that inhibit PNGase F activity.
31913636	2	6	theme	influenza	352:360	arg1	HA					423:424	HA	423:424	HA	423:424	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	2	6	theme	influenza	352:360	arg1	antigen					370:376	the principal influenza vaccine antigen and major viral spike protein hemagglutinin	338:420	antigen	370:376	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	4	7	from	HIV	963:965	arg1	glycoprotein					939:950	the envelope glycoprotein	926:950	the envelope glycoprotein (Env) from HIV	926:965	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	4	7	from	HIV	963:965	arg1	Env					953:955	Env	953:955	Env	953:955	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	7	8	theme	certain	1344:1350	arg1	conditions					1365:1374	certain experimental conditions	1344:1374	certain experimental conditions	1344:1374	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	4	9	theme	glycoproteins/vaccine	884:904	arg1	glycoprotein					939:950	the envelope glycoprotein	926:950	the envelope glycoprotein (Env) from HIV	926:965	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	4	9	theme	glycoproteins/vaccine	884:904	arg1	antigens					906:913	other viral glycoproteins/vaccine antigens	872:913	other viral glycoproteins/vaccine antigens	872:913	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	2	10	theme	N-glycan	304:311	arg1	pruning					293:299	pruning	293:299	pruning of N-glycan by the amidase PNGase F	293:335	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	4	11	theme	viral	878:882	arg1	glycoprotein					939:950	the envelope glycoprotein	926:950	the envelope glycoprotein (Env) from HIV	926:965	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	4	11	theme	viral	878:882	arg1	antigens					906:913	other viral glycoproteins/vaccine antigens	872:913	other viral glycoproteins/vaccine antigens	872:913	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	6	12	theme	retention	1270:1278	arg1	N-glycanation					1295:1307	this retention and subsequent N-glycanation	1265:1307	this retention and subsequent N-glycanation	1265:1307	Rather, N-glycanation relied on a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation.
31913636	5	13	theme	N-glycan	977:984	arg1	reattachment					986:997	Covalent N-glycan reattachment	968:997	Covalent N-glycan reattachment	968:997	Covalent N-glycan reattachment was nonenzymatic as it occurred in the presence of metal ions that inhibit PNGase F activity.
31913636	2	14	theme	principal	342:350	arg1	HA					423:424	HA	423:424	HA	423:424	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	2	14	theme	principal	342:350	arg1	antigen					370:376	the principal influenza vaccine antigen and major viral spike protein hemagglutinin	338:420	antigen	370:376	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	7	15	theme	self-glycan	1409:1419	arg1	addition					1421:1428	self-glycan addition	1409:1428	self-glycan addition	1409:1428	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	7	16	theme	self-assembly	1457:1469	arg1	principle					1471:1479	a remarkable self-assembly principle	1444:1479	a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy	1444:1668	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	2	17	theme	viral	388:392	arg1	hemagglutinin					408:420	the principal influenza vaccine antigen and major viral spike protein hemagglutinin	338:420	hemagglutinin	408:420	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	2	18	theme	protein	400:406	arg1	hemagglutinin					408:420	the principal influenza vaccine antigen and major viral spike protein hemagglutinin	338:420	hemagglutinin	408:420	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	4	19	theme	de-N-glycosylation	766:783	arg1	rounds					756:761	Iterative rounds	746:761	Iterative rounds of de-N-glycosylation followed by N-glycanation	746:809	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	7	20	theme	influenza	1556:1564	arg1	HA					1566:1567	influenza HA	1556:1567	influenza HA	1556:1567	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	2	21	theme	spike	394:398	arg1	hemagglutinin					408:420	the principal influenza vaccine antigen and major viral spike protein hemagglutinin	338:420	hemagglutinin	408:420	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	0	22	theme	Glycan	12:17	arg1	Reattachment					19:30	Spontaneous Glycan Reattachment	0:30	Spontaneous Glycan Reattachment	0:30	Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.
31913636	6	23	theme	glycoprotein	1242:1253	arg1	linearization					1221:1233	linearization	1221:1233	linearization of the glycoprotein	1221:1253	Rather, N-glycanation relied on a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation.
31913636	2	24	theme	PNGase	328:333	arg1	F					335:335	the amidase PNGase F	316:335	the amidase PNGase F	316:335	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	7	25	theme	re-engineering	1507:1520	arg1	glycoproteins					1534:1546	re-engineering therapeutic glycoproteins	1507:1546	re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy	1507:1668	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	7	25	theme	re-engineering	1507:1520	arg1	HA					1566:1567	influenza HA	1556:1567	influenza HA	1556:1567	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	7	25	theme	re-engineering	1507:1520	arg1	Env					1576:1578	HIV Env	1572:1578	HIV Env	1572:1578	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	1	26	theme	attachment	193:202	arg1	process					204:210	an attachment process	190:210	an attachment process that supports proper folding of the nascent polypeptide	190:266	In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide.
31913636	0	27	theme	Spontaneous	0:10	arg1	Reattachment					19:30	Spontaneous Glycan Reattachment	0:30	Spontaneous Glycan Reattachment	0:30	Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.
31913636	2	28	theme	amidase	320:326	arg1	F					335:335	the amidase PNGase F	316:335	the amidase PNGase F	316:335	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	2	29	theme	major	382:386	arg1	hemagglutinin					408:420	the principal influenza vaccine antigen and major viral spike protein hemagglutinin	338:420	hemagglutinin	408:420	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	6	30	theme	subsequent	1284:1293	arg1	N-glycanation					1295:1307	this retention and subsequent N-glycanation	1265:1307	this retention and subsequent N-glycanation	1265:1307	Rather, N-glycanation relied on a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation.
31913636	4	31	theme	Iterative	746:754	arg1	rounds					756:761	Iterative rounds	746:761	Iterative rounds of de-N-glycosylation followed by N-glycanation	746:809	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	3	32	theme	site-specific	601:613	arg1	analysis					615:622	site-specific analysis	601:622	site-specific analysis of HA glycoforms	601:639	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	7	33	theme	remarkable	1446:1455	arg1	principle					1471:1479	a remarkable self-assembly principle	1444:1479	a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy	1444:1668	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	3	34	theme	amidase	729:735	arg1	removal					737:743	amidase removal	729:743	amidase removal	729:743	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	4	35	theme	envelope	930:937	arg1	glycoprotein					939:950	the envelope glycoprotein	926:950	the envelope glycoprotein (Env) from HIV	926:965	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	4	35	theme	envelope	930:937	arg1	Env					953:955	Env	953:955	Env	953:955	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	3	36	theme	prior	662:666	arg1	spectrometry					649:660	mass spectrometry	644:660	mass spectrometry prior to PNGase F exposure	644:687	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	7	37	gly	glycoproteins	1534:1546	arg1	glycoproteins					1534:1546	re-engineering therapeutic glycoproteins	1507:1546	re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy	1507:1668	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	7	37	gly	glycoproteins	1534:1546	arg1	HA					1566:1567	influenza HA	1556:1567	influenza HA	1556:1567	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	7	37	gly	glycoproteins	1534:1546	arg1	Env					1576:1578	HIV Env	1572:1578	HIV Env	1572:1578	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	6	38	theme	noncovalent	1127:1137	arg1	assembly					1139:1146	a noncovalent assembly	1125:1146	a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation	1125:1307	Rather, N-glycanation relied on a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation.
31913636	5	39	theme	F	1081:1081	arg1	activity					1083:1090	PNGase F activity	1074:1090	PNGase F activity	1074:1090	Covalent N-glycan reattachment was nonenzymatic as it occurred in the presence of metal ions that inhibit PNGase F activity.
31913636	0	40	dep	Influenza	67:75	arg1	Antigens					93:100	Vaccine Antigens	85:100	Vaccine Antigens	85:100	Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.
31913636	7	41	theme	HIV	1572:1574	arg1	Env					1576:1578	HIV Env	1572:1578	HIV Env	1572:1578	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	1	42	theme	proper	226:231	arg1	folding					233:239	proper folding	226:239	proper folding of the nascent polypeptide	226:266	In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide.
31913636	0	43	theme	N-Glycanase	42:52	arg1	Treatment					54:62	N-Glycanase Treatment	42:62	N-Glycanase Treatment of Influenza and HIV Vaccine Antigens	42:100	Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.
31913636	3	44	theme	mass	644:647	arg1	spectrometry					649:660	mass spectrometry	644:660	mass spectrometry prior to PNGase F exposure	644:687	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	0	45	theme	Influenza	67:75	arg1	Treatment					54:62	N-Glycanase Treatment	42:62	N-Glycanase Treatment of Influenza and HIV Vaccine Antigens	42:100	Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.
31913636	1	46	gly	glycoproteins	154:166	arg1	glycoproteins					154:166	glycoproteins	154:166	glycoproteins	154:166	In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide.
31913636	1	47	theme	asparagine/N-linked	113:131	arg1	glycans					133:139	asparagine/N-linked glycans	113:139	asparagine/N-linked glycans	113:139	In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide.
31913636	7	48	theme	vaccine	1653:1659	arg1	efficacy					1661:1668	vaccine efficacy	1653:1668	vaccine efficacy	1653:1668	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	5	49	theme	metal	1050:1054	arg1	ions					1056:1059	metal ions	1050:1059	metal ions that inhibit PNGase F activity	1050:1090	Covalent N-glycan reattachment was nonenzymatic as it occurred in the presence of metal ions that inhibit PNGase F activity.
31913636	2	50	gly	de-N-glycosylated	468:484	arg1	positions					486:494	its de-N-glycosylated positions	464:494	its de-N-glycosylated positions	464:494	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	7	51	theme	experimental	1352:1363	arg1	conditions					1365:1374	certain experimental conditions	1344:1374	certain experimental conditions	1344:1374	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	4	52	gly	glycoprotein	939:950	arg1	glycoprotein					939:950	the envelope glycoprotein	926:950	the envelope glycoprotein (Env) from HIV	926:965	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	4	52	gly	glycoprotein	939:950	arg1	Env					953:955	Env	953:955	Env	953:955	Iterative rounds of de-N-glycosylation followed by N-glycanation could be repeated at least three times and were observed for other viral glycoproteins/vaccine antigens, including the envelope glycoprotein (Env) from HIV.
31913636	7	53	theme	glycan	1587:1592	arg1	sequence					1594:1601	glycan sequence	1587:1601	glycan sequence	1587:1601	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	1	54	link	asparagine/N-linked	113:131	arg1	glycans					133:139	asparagine/N-linked glycans	113:139	asparagine/N-linked glycans	113:139	In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide.
31913636	5	55	theme	ions	1056:1059	arg1	presence					1038:1045	the presence	1034:1045	the presence of metal ions that inhibit PNGase F activity	1034:1090	Covalent N-glycan reattachment was nonenzymatic as it occurred in the presence of metal ions that inhibit PNGase F activity.
31913636	3	56	theme	glycoforms	630:639	arg1	analysis					615:622	site-specific analysis	601:622	site-specific analysis of HA glycoforms	601:639	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	3	57	theme	PNGase	671:676	arg1	F					678:678	PNGase F	671:678	PNGase F exposure	671:687	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	5	58	theme	Covalent	968:975	arg1	reattachment					986:997	Covalent N-glycan reattachment	968:997	Covalent N-glycan reattachment	968:997	Covalent N-glycan reattachment was nonenzymatic as it occurred in the presence of metal ions that inhibit PNGase F activity.
31913636	6	59	gly	glycoprotein	1242:1253	arg1	glycoprotein					1242:1253	the glycoprotein	1238:1253	the glycoprotein	1238:1253	Rather, N-glycanation relied on a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation.
31913636	0	60	theme	HIV	81:83	arg1	Treatment					54:62	N-Glycanase Treatment	42:62	N-Glycanase Treatment of Influenza and HIV Vaccine Antigens	42:100	Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens.
31913636	3	61	theme	F	678:678	arg1	exposure					680:687	PNGase F exposure	671:687	PNGase F exposure	671:687	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	2	62	attach	removed	517:523	arg1	solution					530:537	solution	530:537	solution	530:537	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	2	62	attach	removed	517:523	arg2	amidase					505:511	the amidase	501:511	the amidase	501:511	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	3	63	gly	glycoforms	630:639	arg1	HA					627:628	HA glycoforms	627:639	HA glycoforms	627:639	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	1	64	theme	nascent	248:254	arg1	polypeptide					256:266	the nascent polypeptide	244:266	the nascent polypeptide	244:266	In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide.
31913636	2	65	theme	de-N-glycosylated	468:484	arg1	positions					486:494	its de-N-glycosylated positions	464:494	its de-N-glycosylated positions	464:494	We found that following pruning of N-glycan by the amidase PNGase F, the principal influenza vaccine antigen and major viral spike protein hemagglutinin (HA) spontaneously reattached N-glycan to its de-N-glycosylated positions when the amidase was removed from solution.
31913636	7	66	gly	glycoproteins	1382:1394	arg1	glycoproteins					1382:1394	some glycoproteins	1377:1394	some glycoproteins	1377:1394	This reaction suggests that under certain experimental conditions, some glycoproteins can organize self-glycan addition, highlighting a remarkable self-assembly principle that may prove useful for re-engineering therapeutic glycoproteins such as influenza HA or HIV Env, where glycan sequence and structure can markedly affect bioactivity and vaccine efficacy.
31913636	3	67	theme	HA	627:628	arg1	glycoforms					630:639	HA glycoforms	627:639	HA glycoforms	627:639	This reaction, which we term N-glycanation, was confirmed by site-specific analysis of HA glycoforms by mass spectrometry prior to PNGase F exposure, during exposure to PNGase F, and after amidase removal.
31913636	6	68	theme	amidase	1206:1212	arg1	presence					1190:1197	the presence	1186:1197	the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation	1186:1307	Rather, N-glycanation relied on a noncovalent assembly between protein and glycan, formed in the presence of the amidase, where linearization of the glycoprotein prevented this retention and subsequent N-glycanation.
31913636	1	69	theme	polypeptide	256:266	arg1	folding					233:239	proper folding	226:239	proper folding of the nascent polypeptide	226:266	In cells, asparagine/N-linked glycans are added to glycoproteins cotranslationally, in an attachment process that supports proper folding of the nascent polypeptide.
31616924	2	0	attach	attaches	331:338	arg2	APOE					326:329	plasma APOE	319:329	plasma APOE	319:329	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	2	0	attach	attaches	331:338	arg1	lipoproteins					343:354	lipoproteins	343:354	lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop	343:418	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	9	1	theme	branched	1517:1524	arg1	glycosylation					1485:1497	C-terminal glycosylation	1474:1497	C-terminal glycosylation	1474:1497	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	9	1	theme	branched	1517:1524	arg1	structure					1539:1547	the branched disialylated structure	1513:1547	particularly the branched disialylated structure	1500:1547	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	1	2	theme	risk	170:173	arg1	factor					175:180	the strongest genetic risk factor	148:180	the strongest genetic risk factor for Alzheimer's disease	148:204	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	1	2	theme	risk	170:173	arg1	E					138:138	The O-glycoprotein apolipoprotein E	104:138	The O-glycoprotein apolipoprotein E (APOE)	104:145	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	5	3	gly	O-glycosylated	850:863	arg1	APOE					842:845	APOE	842:845	APOE	842:845	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	3	gly	O-glycosylated	850:863	arg2	Thr18					889:893	Thr18	889:893	Thr18	889:893	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	3	gly	O-glycosylated	850:863	arg2	Thr289					912:917	Thr289	912:917	Thr289	912:917	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	3	gly	O-glycosylated	850:863	arg2	sites					876:880	several sites	868:880	several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296	868:936	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	3	gly	O-glycosylated	850:863	arg2	Ser290					920:925	Ser290	920:925	Ser290	920:925	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	3	gly	O-glycosylated	850:863	arg2	Ser197					904:909	Ser197	904:909	Ser197	904:909	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	3	gly	O-glycosylated	850:863	arg2	Ser296					931:936	Ser296	931:936	Ser296	931:936	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	6	4	theme	Plasma	939:944	arg1	APOE					946:949	Plasma APOE	939:949	Plasma APOE	939:949	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	4	5	theme	Detailed	614:621	arg1	analyses					632:639	Detailed LC-MS/MS analyses	614:639	Detailed LC-MS/MS analyses	614:639	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	2	6	theme	high-density	279:290	arg1	lipoproteins					292:303	only high-density lipoproteins	274:303	only high-density lipoproteins (HDLs)	274:310	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	2	6	theme	high-density	279:290	arg1	HDLs					306:309	HDLs	306:309	HDLs	306:309	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	8	7	dep	C-terminal	1224:1233	arg1	Ser296					1255:1260	Ser296	1255:1260	Ser296	1255:1260	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	7	dep	C-terminal	1224:1233	arg1	Ser290					1244:1249	Ser290	1244:1249	Ser290	1244:1249	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	7	dep	C-terminal	1224:1233	arg1	Thr289					1236:1241	Thr289	1236:1241	Thr289	1236:1241	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	11	8	theme	HDL	1768:1770	arg1	binding					1772:1778	HDL binding	1768:1778	HDL binding	1768:1778	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	11	9	theme	APOE	1834:1837	arg1	domain					1820:1825	the lipid-binding domain	1802:1825	the lipid-binding domain of CSF APOE	1802:1837	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	11	9	theme	APOE	1834:1837	arg1	APOE					1834:1837	CSF APOE	1830:1837	CSF APOE	1830:1837	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	9	10	theme	receptor-binding	1594:1609	arg1	domain					1611:1616	the receptor-binding domain	1590:1616	the receptor-binding domain	1590:1616	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	4	11	gly	glycosite	675:683	arg2	glycosite					675:683	the glycosite	671:683	the glycosite	671:683	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	12	theme	site	713:716	arg1	occupancy					718:726	the attached glycan and site occupancy	689:726	occupancy	718:726	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	3	13	theme	individuals	601:611	arg1	plasma					578:583	plasma	578:583	plasma	578:583	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	3	13	theme	individuals	601:611	arg1	CSF					589:591	CSF	589:591	CSF	589:591	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	5	14	from	sites	876:880	arg1	O-glycosylated					850:863	O-glycosylated	850:863	O-glycosylated	850:863	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	8	15	theme	CSF	1181:1183	arg1	APOE					1185:1188	CSF APOE	1181:1188	CSF APOE	1181:1188	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	4	16	theme	glycosite	675:683	arg1	glycan					702:707	the attached glycan and site occupancy	689:726	glycan	702:707	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	16	theme	glycosite	675:683	arg1	occupancy					718:726	the attached glycan and site occupancy	689:726	occupancy	718:726	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	16	theme	glycosite	675:683	arg1	identification					653:666	the identification	649:666	the identification of the glycosite	649:683	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	10	17	theme	tissue-specific	1687:1701	arg1	glycoforms					1708:1717	tissue-specific APOE glycoforms	1687:1717	tissue-specific APOE glycoforms	1687:1717	These data, although limited by sample size, suggest that there are tissue-specific APOE glycoforms.
31616924	8	18	dep	glycosylation	1263:1275	arg1	%					1282:1282	36.8%	1278:1282	36.8% of CSF peptide283-299 was glycosylated	1278:1321	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	18	dep	glycosylation	1263:1275	arg1	peptide283-299					1339:1352	plasma peptide283-299	1332:1352	plasma peptide283-299	1332:1352	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	18	dep	glycosylation	1263:1275	arg1	%					1327:1327	3.8%	1324:1327	3.8% of plasma peptide283-299	1324:1352	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	19	theme	peptide283-299	1339:1352	arg1	%					1327:1327	3.8%	1324:1327	3.8% of plasma peptide283-299	1324:1352	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	19	theme	peptide283-299	1339:1352	arg1	peptide283-299					1339:1352	plasma peptide283-299	1332:1352	plasma peptide283-299	1332:1352	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	19	theme	peptide283-299	1339:1352	arg1	%					1282:1282	36.8%	1278:1282	36.8% of CSF peptide283-299 was glycosylated	1278:1321	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	12	20	theme	lipoprotein-binding	1927:1945	arg1	flexibility					1947:1957	lipoprotein-binding flexibility	1927:1957	lipoprotein-binding flexibility	1927:1957	This indicates that APOE glycosylation may be implicated in lipoprotein-binding flexibility.
31616924	1	21	theme	strongest	152:160	arg1	factor					175:180	the strongest genetic risk factor	148:180	the strongest genetic risk factor for Alzheimer's disease	148:204	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	1	21	theme	strongest	152:160	arg1	E					138:138	The O-glycoprotein apolipoprotein E	104:138	The O-glycoprotein apolipoprotein E (APOE)	104:145	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	0	22	from	O-glycosylation	0:14	arg1	fluid					33:37	cerebrospinal fluid	19:37	cerebrospinal fluid	19:37	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	0	22	from	O-glycosylation	0:14	arg1	E					65:65	plasma apolipoprotein E	43:65	plasma apolipoprotein E	43:65	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	8	23	theme	abundant	1215:1222	arg1	glycosylation					1263:1275	almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation	1195:1275	almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299)	1195:1353	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	3	24	attach	isolated	560:567	arg1	plasma					578:583	plasma	578:583	plasma	578:583	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	3	24	attach	isolated	560:567	arg2	APOE					555:558	APOE	555:558	APOE isolated from the plasma and CSF of aged individuals	555:611	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	3	24	attach	isolated	560:567	arg1	CSF					589:591	CSF	589:591	CSF	589:591	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	8	25	theme	disialylated	1376:1387	arg1	structures					1438:1447	disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures	1376:1447	disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures	1376:1447	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	2	26	theme	diverse	359:365	arg1	sizes					367:371	diverse sizes	359:371	diverse sizes	359:371	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	4	27	gly	glycoforms	822:831	arg1	APOE					836:839	APOE	836:839	APOE	836:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	2	28	theme	Cerebrospinal	237:249	arg1	fluid					251:255	Cerebrospinal fluid	237:255	Cerebrospinal fluid (CSF) APOE	237:266	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	2	28	theme	Cerebrospinal	237:249	arg1	CSF					258:260	CSF	258:260	CSF	258:260	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	6	29	theme	core	1007:1010	arg1	glycosylation					1043:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	2	30	theme	fluid	251:255	arg1	APOE					263:266	Cerebrospinal fluid (CSF) APOE	237:266	Cerebrospinal fluid (CSF) APOE	237:266	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	4	31	theme	detectable	736:745	arg1	glycoforms					822:831	physiological glycoforms	808:831	physiological glycoforms of APOE	808:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	31	theme	detectable	736:745	arg1	glycosites					747:756	all detectable glycosites	732:756	all detectable glycosites on APOE	732:764	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	3	32	gly	O-glycosylation	446:460	arg1	differences					492:502	differences	492:502	differences across tissues	492:517	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	3	32	gly	O-glycosylation	446:460	arg1	molecule					479:486	this critical molecule	465:486	this critical molecule	465:486	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	0	33	theme	cerebrospinal	19:31	arg1	fluid					33:37	cerebrospinal fluid	19:37	cerebrospinal fluid	19:37	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	1	34	theme	O-glycoprotein	108:121	arg1	factor					175:180	the strongest genetic risk factor	148:180	the strongest genetic risk factor for Alzheimer's disease	148:204	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	1	34	theme	O-glycoprotein	108:121	arg1	APOE					141:144	APOE	141:144	APOE	141:144	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	1	34	theme	O-glycoprotein	108:121	arg1	E					138:138	The O-glycoprotein apolipoprotein E	104:138	The O-glycoprotein apolipoprotein E (APOE)	104:145	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	4	35	theme	glycoforms	822:831	arg1	modeling					796:803	further three-dimensional modeling	770:803	further three-dimensional modeling of physiological glycoforms of APOE	770:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	35	theme	glycoforms	822:831	arg1	glycoforms					822:831	physiological glycoforms	808:831	physiological glycoforms of APOE	808:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	35	theme	glycoforms	822:831	arg1	glycosites					747:756	all detectable glycosites	732:756	all detectable glycosites on APOE	732:764	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	36	theme	APOE	836:839	arg1	glycoforms					822:831	physiological glycoforms	808:831	physiological glycoforms of APOE	808:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	2	37	theme	plasma	319:324	arg1	APOE					326:329	plasma APOE	319:329	plasma APOE	319:329	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	0	38	theme	apolipoprotein	50:63	arg1	E					65:65	plasma apolipoprotein E	43:65	plasma apolipoprotein E	43:65	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	8	39	theme	core	1431:1434	arg1	structures					1438:1447	disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures	1376:1447	disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures	1376:1447	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	4	40	theme	three-dimensional	778:794	arg1	modeling					796:803	further three-dimensional modeling	770:803	further three-dimensional modeling of physiological glycoforms of APOE	770:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	3	41	from	O-glycosylation	446:460	arg1	differences					492:502	differences	492:502	differences across tissues	492:517	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	3	41	from	O-glycosylation	446:460	arg1	molecule					479:486	this critical molecule	465:486	this critical molecule	465:486	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	11	42	theme	Sialylated	1720:1729	arg1	glycans					1731:1737	Sialylated glycans	1720:1737	Sialylated glycans	1720:1737	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	10	43	gly	glycoforms	1708:1717	arg1	APOE					1703:1706	tissue-specific APOE glycoforms	1687:1717	tissue-specific APOE glycoforms	1687:1717	These data, although limited by sample size, suggest that there are tissue-specific APOE glycoforms.
31616924	2	44	with	lipoproteins	343:354	arg1	binding					378:384	binding	378:384	binding fine-tuned by the C-terminal loop	378:418	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	9	45	theme	C-terminal	1474:1483	arg1	glycosylation					1485:1497	C-terminal glycosylation	1474:1497	C-terminal glycosylation	1474:1497	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	9	45	theme	C-terminal	1474:1483	arg1	structure					1539:1547	the branched disialylated structure	1513:1547	particularly the branched disialylated structure	1500:1547	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	6	46	theme	CSF	1069:1071	arg1	APOE					1073:1076	CSF APOE	1069:1076	CSF APOE (0.1%)	1069:1083	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	6	46	theme	CSF	1069:1071	arg1	%					1082:1082	0.1%	1079:1082	0.1%	1079:1082	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	8	47	theme	CSF	1287:1289	arg1	peptide283-299					1291:1304	CSF peptide283-299	1287:1304	CSF peptide283-299	1287:1304	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	5	48	theme	several	868:874	arg1	Ser197					904:909	Ser197	904:909	Ser197	904:909	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	48	theme	several	868:874	arg1	Ser296					931:936	Ser296	931:936	Ser296	931:936	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	48	theme	several	868:874	arg1	Thr18					889:893	Thr18	889:893	Thr18	889:893	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	48	theme	several	868:874	arg1	Thr289					912:917	Thr289	912:917	Thr289	912:917	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	48	theme	several	868:874	arg1	Ser290					920:925	Ser290	920:925	Ser290	920:925	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	48	theme	several	868:874	arg1	sites					876:880	several sites	868:880	several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296	868:936	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	9	49	theme	disialylated	1526:1537	arg1	glycosylation					1485:1497	C-terminal glycosylation	1474:1497	C-terminal glycosylation	1474:1497	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	9	49	theme	disialylated	1526:1537	arg1	structure					1539:1547	the branched disialylated structure	1513:1547	particularly the branched disialylated structure	1500:1547	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	3	50	theme	critical	470:477	arg1	molecule					479:486	this critical molecule	465:486	this critical molecule	465:486	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	8	51	gly	glycosylated	1310:1321	arg1	%					1282:1282	36.8%	1278:1282	36.8% of CSF peptide283-299 was glycosylated	1278:1321	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	51	gly	glycosylated	1310:1321	arg1	peptide283-299					1291:1304	CSF peptide283-299	1287:1304	CSF peptide283-299	1287:1304	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	51	gly	glycosylated	1310:1321	arg1	peptide283-299					1339:1352	plasma peptide283-299	1332:1352	plasma peptide283-299	1332:1352	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	51	gly	glycosylated	1310:1321	arg1	%					1327:1327	3.8%	1324:1327	3.8% of plasma peptide283-299	1324:1352	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	1	52	theme	genetic	162:168	arg1	factor					175:180	the strongest genetic risk factor	148:180	the strongest genetic risk factor for Alzheimer's disease	148:204	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	1	52	theme	genetic	162:168	arg1	E					138:138	The O-glycoprotein apolipoprotein E	104:138	The O-glycoprotein apolipoprotein E (APOE)	104:145	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	3	53	dep	plasma	578:583	arg1	the					574:576	the	574:576	the	574:576	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	10	54	theme	sample	1651:1656	arg1	size					1658:1661	sample size	1651:1661	sample size	1651:1661	These data, although limited by sample size, suggest that there are tissue-specific APOE glycoforms.
31616924	10	55	dep	suggest	1664:1670	arg1	limited					1640:1646	limited	1640:1646	limited by sample size	1640:1661	These data, although limited by sample size, suggest that there are tissue-specific APOE glycoforms.
31616924	11	56	theme	CSF	1830:1832	arg1	APOE					1834:1837	CSF APOE	1830:1837	CSF APOE	1830:1837	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	8	57	dep	abundant	1215:1222	arg1	C-terminal					1224:1233	C-terminal	1224:1233	C-terminal	1224:1233	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	4	58	theme	LC-MS/MS	623:630	arg1	analyses					632:639	Detailed LC-MS/MS analyses	614:639	Detailed LC-MS/MS analyses	614:639	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	1	59	theme	apolipoprotein	123:136	arg1	factor					175:180	the strongest genetic risk factor	148:180	the strongest genetic risk factor for Alzheimer's disease	148:204	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	1	59	theme	apolipoprotein	123:136	arg1	APOE					141:144	APOE	141:144	APOE	141:144	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	1	59	theme	apolipoprotein	123:136	arg1	E					138:138	The O-glycoprotein apolipoprotein E	104:138	The O-glycoprotein apolipoprotein E (APOE)	104:145	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	6	60	dep	abundant	961:968	arg1	%					975:975	20.5%	971:975	20.5%	971:975	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	6	60	dep	abundant	961:968	arg1	N-terminal					978:987	N-terminal	978:987	N-terminal	978:987	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	4	61	theme	attached	693:700	arg1	glycan					702:707	the attached glycan and site occupancy	689:726	glycan	702:707	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	3	62	from	O-glycosylation	536:550	arg1	APOE					555:558	APOE	555:558	APOE isolated from the plasma and CSF of aged individuals	555:611	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	7	63	gly	glycosylated	1108:1119	arg1	%					1158:1158	27.3%	1154:1158	27.3%	1154:1158	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	7	63	gly	glycosylated	1108:1119	arg1	%					1177:1177	10.3%	1173:1177	10.3%	1173:1177	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	7	63	gly	glycosylated	1108:1119	arg2	APOE					1086:1089	APOE	1086:1089	APOE	1086:1089	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	7	63	gly	glycosylated	1108:1119	arg1	CSF					1149:1151	CSF	1149:1151	CSF (27.3%)	1149:1159	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	7	63	gly	glycosylated	1108:1119	arg1	plasma					1165:1170	plasma	1165:1170	plasma (10.3%)	1165:1178	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	7	63	gly	glycosylated	1108:1119	arg1	APOE					1086:1089	APOE	1086:1089	APOE	1086:1089	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	3	64	theme	aged	596:599	arg1	individuals					601:611	aged individuals	596:611	aged individuals	596:611	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	8	65	dep	%	1282:1282	arg1	glycosylated					1310:1321	glycosylated	1310:1321	was glycosylated	1306:1321	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	8	66	theme	plasma	1332:1337	arg1	peptide283-299					1339:1352	plasma peptide283-299	1332:1352	plasma peptide283-299	1332:1352	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	3	67	gly	O-glycosylation	536:550	arg1	APOE					555:558	APOE	555:558	APOE isolated from the plasma and CSF of aged individuals	555:611	To better understand the O-glycosylation on this critical molecule and differences across tissues, we analyzed the O-glycosylation on APOE isolated from the plasma and CSF of aged individuals.
31616924	4	68	gly	glycosites	747:756	arg1	glycoforms					822:831	physiological glycoforms	808:831	physiological glycoforms of APOE	808:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	68	gly	glycosites	747:756	arg2	glycoforms					822:831	physiological glycoforms	808:831	physiological glycoforms of APOE	808:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	68	gly	glycosites	747:756	arg2	glycosites					747:756	all detectable glycosites	732:756	all detectable glycosites on APOE	732:764	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	10	69	theme	APOE	1703:1706	arg1	glycoforms					1708:1717	tissue-specific APOE glycoforms	1687:1717	tissue-specific APOE glycoforms	1687:1717	These data, although limited by sample size, suggest that there are tissue-specific APOE glycoforms.
31616924	4	70	from	modeling	796:803	arg1	APOE					761:764	APOE	761:764	APOE	761:764	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	0	71	theme	lipid-binding	82:94	arg1	domain					96:101	the lipid-binding domain	78:101	the lipid-binding domain	78:101	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	8	72	gly	disialylated	1376:1387	arg1	structures					1438:1447	disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures	1376:1447	disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures	1376:1447	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	4	73	gly	occupancy	718:726	arg2	site					713:716	the attached glycan and site occupancy	689:726	site	713:716	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	73	gly	occupancy	718:726	arg1	glycosite					675:683	the glycosite	671:683	the glycosite	671:683	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	4	73	gly	occupancy	718:726	arg2	glycosite					675:683	the glycosite	671:683	the glycosite	671:683	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	7	74	dep	glycosylated	1108:1119	arg1	Ser197					1133:1138	Ser197	1133:1138	Ser197	1133:1138	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	7	74	dep	glycosylated	1108:1119	arg1	domain					1101:1106	hinge domain	1095:1106	hinge domain	1095:1106	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	7	74	dep	glycosylated	1108:1119	arg1	Thr194					1122:1127	Thr194	1122:1127	Thr194	1122:1127	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
31616924	1	75	gly	O-glycoprotein	108:121	arg1	O-glycoprotein					108:121	The O-glycoprotein apolipoprotein E	104:138	The O-glycoprotein apolipoprotein E (APOE)	104:145	The O-glycoprotein apolipoprotein E (APOE), the strongest genetic risk factor for Alzheimer's disease, associates with lipoproteins.
31616924	4	76	from	glycosites	747:756	arg1	APOE					761:764	APOE	761:764	APOE	761:764	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	6	77	theme	Neu5Acα2-3Galβ1-3GalNAcα1-	1015:1040	arg1	glycosylation					1043:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	6	78	dep	N-terminal	978:987	arg1	compared					1057:1064	compared	1057:1064	compared to CSF APOE (0.1%)	1057:1083	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	6	78	dep	N-terminal	978:987	arg1	Thr8					990:993	Thr8	990:993	Thr8	990:993	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	5	79	dep	sites	876:880	arg1	Ser197					904:909	Ser197	904:909	Ser197	904:909	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	79	dep	sites	876:880	arg1	Ser296					931:936	Ser296	931:936	Ser296	931:936	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	79	dep	sites	876:880	arg1	Thr18					889:893	Thr18	889:893	Thr18	889:893	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	79	dep	sites	876:880	arg1	Thr289					912:917	Thr289	912:917	Thr289	912:917	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	79	dep	sites	876:880	arg1	Ser290					920:925	Ser290	920:925	Ser290	920:925	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	5	79	dep	sites	876:880	arg1	sites					876:880	several sites	868:880	several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296	868:936	APOE is O-glycosylated at several sites: Thr8, Thr18, Thr194, Ser197, Thr289, Ser290 and Ser296.
31616924	2	80	theme	sizes	367:371	arg1	lipoproteins					343:354	lipoproteins	343:354	lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop	343:418	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	6	81	theme	sialylated	996:1005	arg1	glycosylation					1043:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	2	82	theme	C-terminal	404:413	arg1	loop					415:418	the C-terminal loop	400:418	the C-terminal loop	400:418	Cerebrospinal fluid (CSF) APOE binds only high-density lipoproteins (HDLs), while plasma APOE attaches to lipoproteins of diverse sizes with binding fine-tuned by the C-terminal loop.
31616924	6	83	gly	sialylated	996:1005	arg1	glycosylation					1043:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation	996:1055	Plasma APOE held more abundant (20.5%) N-terminal (Thr8) sialylated core 1 (Neu5Acα2-3Galβ1-3GalNAcα1-) glycosylation compared to CSF APOE (0.1%).
31616924	11	84	theme	lipid-binding	1806:1818	arg1	domain					1820:1825	the lipid-binding domain	1802:1825	the lipid-binding domain of CSF APOE	1802:1837	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	11	84	theme	lipid-binding	1806:1818	arg1	APOE					1834:1837	CSF APOE	1830:1837	CSF APOE	1830:1837	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	0	85	theme	plasma	43:48	arg1	E					65:65	plasma apolipoprotein E	43:65	plasma apolipoprotein E	43:65	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	0	86	gly	O-glycosylation	0:14	arg1	fluid					33:37	cerebrospinal fluid	19:37	cerebrospinal fluid	19:37	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	0	86	gly	O-glycosylation	0:14	arg1	E					65:65	plasma apolipoprotein E	43:65	plasma apolipoprotein E	43:65	O-glycosylation on cerebrospinal fluid and plasma apolipoprotein E differs in the lipid-binding domain.
31616924	4	87	theme	physiological	808:820	arg1	glycoforms					822:831	physiological glycoforms	808:831	physiological glycoforms of APOE	808:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	12	88	gly	glycosylation	1892:1904	arg1	flexibility					1947:1957	lipoprotein-binding flexibility	1927:1957	lipoprotein-binding flexibility	1927:1957	This indicates that APOE glycosylation may be implicated in lipoprotein-binding flexibility.
31616924	4	89	theme	further	770:776	arg1	modeling					796:803	further three-dimensional modeling	770:803	further three-dimensional modeling of physiological glycoforms of APOE	770:839	Detailed LC-MS/MS analyses allowed the identification of the glycosite and the attached glycan and site occupancy for all detectable glycosites on APOE and further three-dimensional modeling of physiological glycoforms of APOE.
31616924	11	90	theme	plasma	1854:1859	arg1	APOE					1861:1864	plasma APOE	1854:1864	plasma APOE	1854:1864	Sialylated glycans, previously shown to improve HDL binding, are more abundant on the lipid-binding domain of CSF APOE and reduced in plasma APOE.
31616924	9	91	gly	disialylated	1526:1537	arg1	glycosylation					1485:1497	C-terminal glycosylation	1474:1497	C-terminal glycosylation	1474:1497	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	9	91	gly	disialylated	1526:1537	arg1	structure					1539:1547	the branched disialylated structure	1513:1547	particularly the branched disialylated structure	1500:1547	Modeling suggested that C-terminal glycosylation, particularly the branched disialylated structure, could interact across domains including the receptor-binding domain.
31616924	8	92	dep	disialylated	1376:1387	arg1	GalNAcα1-					1420:1428	GalNAcα1-	1420:1428	GalNAcα1-	1420:1428	CSF APOE held almost 10-fold more abundant C-terminal (Thr289, Ser290 and Ser296) glycosylation (36.8% of CSF peptide283-299 was glycosylated, 3.8% of plasma peptide283-299), with sialylated and disialylated (Neu5Acα2-3Galβ1-3(Neu5Acα2-6) GalNAcα1-) core 1 structures.
31616924	12	93	theme	APOE	1887:1890	arg1	glycosylation					1892:1904	APOE glycosylation	1887:1904	APOE glycosylation	1887:1904	This indicates that APOE glycosylation may be implicated in lipoprotein-binding flexibility.
31616924	7	94	theme	hinge	1095:1099	arg1	domain					1101:1106	hinge domain	1095:1106	hinge domain	1095:1106	APOE was hinge domain glycosylated (Thr194 and Ser197) in both CSF (27.3%) and plasma (10.3%).
34726367	7	0	theme	Mouse	1136:1140	arg1	vaccination					1142:1152	Mouse vaccination	1136:1152	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide	1136:1218	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	3	1	theme	Mass	526:529	arg1	analyses					545:552	Mass spectrometric analyses	526:552	Mass spectrometric analyses	526:552	Mass spectrometric analyses indicated these isolates express a hexasaccharide lacking the glucose branch.
34726367	2	2	from	infants	288:294	arg1	isolates					274:281	98 C. jejuni isolates	261:281	98 C. jejuni isolates from infants from 7 low- and middle-income countries	261:334	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	6	3	theme	Molecular	1008:1016	arg1	modeling					1018:1025	Molecular modeling	1008:1025	Molecular modeling	1008:1025	Molecular modeling proposed a mechanism for how the DXDD residues and the structure/length beyond the motif influence activity.
34726367	2	4	theme	Glc	497:499	arg1	-GalNAc-GalNAc-diNAcBac					501:523	GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	476:523	GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	476:523	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	3	5	theme	spectrometric	531:543	arg1	analyses					545:552	Mass spectrometric analyses	526:552	Mass spectrometric analyses	526:552	Mass spectrometric analyses indicated these isolates express a hexasaccharide lacking the glucose branch.
34726367	7	6	theme	N-glycan-specific	1229:1245	arg1	antibodies					1247:1256	N-glycan-specific antibodies	1229:1256	N-glycan-specific antibodies	1229:1256	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	4	7	theme	present	764:770	arg1	alteration					748:757	an alteration	745:757	an alteration also present in ∼4% of all available PglI sequences	745:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	7	theme	present	764:770	arg1	aspartate					704:712	one aspartate	700:712	one aspartate in the DXDD motif	700:730	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	7	8	theme	weight	1322:1327	arg1	loss					1329:1332	weight loss	1322:1332	weight loss	1322:1332	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	4	9	from	%	777:777	arg1	present					764:770	present	764:770	present	764:770	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	5	10	theme	protein	897:903	arg1	system					919:924	the protein glycosylation system	893:924	the protein glycosylation system	893:924	Deleting this residue from an active PglI resulted in a nonfunctional GlcTF when the protein glycosylation system was reconstituted in E. coli, while replacement with Glu/Ala was not deleterious.
34726367	4	11	from	aspartate	704:712	arg1	motif					726:730	the DXDD motif	717:730	the DXDD motif	717:730	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	5	12	theme	active	842:847	arg1	PglI					849:852	an active PglI	839:852	an active PglI	839:852	Deleting this residue from an active PglI resulted in a nonfunctional GlcTF when the protein glycosylation system was reconstituted in E. coli, while replacement with Glu/Ala was not deleterious.
34726367	2	13	from	countries	326:334	arg1	isolates					274:281	98 C. jejuni isolates	261:281	98 C. jejuni isolates from infants from 7 low- and middle-income countries	261:334	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	1	14	theme	Campylobacter	79:91	arg1	jejuni					93:98	Campylobacter jejuni	79:98	Campylobacter jejuni	79:98	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	1	14	theme	Campylobacter	79:91	arg1	cause					117:121	a significant cause	103:121	a significant cause of human gastroenteritis worldwide	103:156	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	5	15	theme	glycosylation	905:917	arg1	system					919:924	the protein glycosylation system	893:924	the protein glycosylation system	893:924	Deleting this residue from an active PglI resulted in a nonfunctional GlcTF when the protein glycosylation system was reconstituted in E. coli, while replacement with Glu/Ala was not deleterious.
34726367	7	16	theme	E.	1162:1163	arg1	strain					1170:1175	an E. coli strain	1159:1175	an E. coli strain expressing the full-length heptasaccharide	1159:1218	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	2	17	theme	C.	264:265	arg1	isolates					274:281	98 C. jejuni isolates	261:281	98 C. jejuni isolates from infants from 7 low- and middle-income countries	261:334	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	7	18	with	vaccination	1142:1152	arg1	strain					1170:1175	an E. coli strain	1159:1175	an E. coli strain expressing the full-length heptasaccharide	1159:1218	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	2	19	theme	N-glycan-specific	382:398	arg1	antiserum					400:408	our N-glycan-specific antiserum	378:408	our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	378:523	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	0	20	theme	Glucose	10:16	arg1	Fluctuations					18:29	Glucose Fluctuations	10:29	Glucose Fluctuations	10:29	Detecting Glucose Fluctuations in the Campylobacter jejuni N-Glycan Structure.
34726367	7	21	dep	E.	1162:1163	arg1	coli					1165:1168	coli	1165:1168	coli	1165:1168	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	4	22	from	present	764:770	arg1	sequences					801:809	all available PglI sequences	782:809	all available PglI sequences	782:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	22	from	present	764:770	arg1	%					777:777	∼4%	775:777	∼4% of all available PglI sequences	775:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	2	23	theme	low-	303:306	arg1	countries					326:334	7 low- and middle-income countries	301:334	7 low- and middle-income countries	301:334	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	5	24	theme	nonfunctional	868:880	arg1	GlcTF					882:886	a nonfunctional GlcTF	866:886	a nonfunctional GlcTF	866:886	Deleting this residue from an active PglI resulted in a nonfunctional GlcTF when the protein glycosylation system was reconstituted in E. coli, while replacement with Glu/Ala was not deleterious.
34726367	3	25	theme	glucose	616:622	arg1	branch					624:629	the glucose branch	612:629	the glucose branch	612:629	Mass spectrometric analyses indicated these isolates express a hexasaccharide lacking the glucose branch.
34726367	2	26	theme	C.	438:439	arg1	jejuni					441:446	the C. jejuni heptasaccharide	434:462	the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	434:523	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	1	27	theme	significant	105:115	arg1	jejuni					93:98	Campylobacter jejuni	79:98	Campylobacter jejuni	79:98	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	1	27	theme	significant	105:115	arg1	cause					117:121	a significant cause	103:121	a significant cause of human gastroenteritis worldwide	103:156	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	6	28	theme	DXDD	1060:1063	arg1	residues					1065:1072	the DXDD residues	1056:1072	the DXDD residues	1056:1072	Molecular modeling proposed a mechanism for how the DXDD residues and the structure/length beyond the motif influence activity.
34726367	2	29	theme	jejuni	267:272	arg1	isolates					274:281	98 C. jejuni isolates	261:281	98 C. jejuni isolates from infants from 7 low- and middle-income countries	261:334	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	4	30	theme	DXDD	721:724	arg1	motif					726:730	the DXDD motif	717:730	the DXDD motif	717:730	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	31	theme	PglI	666:669	arg1	strains					647:653	all 4 strains	641:653	all 4 strains	641:653	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	31	theme	PglI	666:669	arg1	GlcTF					692:696	GlcTF	692:696	GlcTF	692:696	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	31	theme	PglI	666:669	arg1	glucosyltransferase					671:689	the PglI glucosyltransferase	662:689	the PglI glucosyltransferase (GlcTF)	662:697	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	0	32	theme	Campylobacter	38:50	arg1	Structure					68:76	the Campylobacter jejuni N-Glycan Structure	34:76	the Campylobacter jejuni N-Glycan Structure	34:76	Detecting Glucose Fluctuations in the Campylobacter jejuni N-Glycan Structure.
34726367	2	33	theme	GalNAc-GalNAc-GalNAc	476:495	arg1	-GalNAc-GalNAc-diNAcBac					501:523	GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	476:523	GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	476:523	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	8	34	theme	jejuni	1447:1452	arg1	isolates					1454:1461	C. jejuni isolates	1444:1461	C. jejuni isolates lacking glucose	1444:1477	However, the antibodies did not recognize the hexasaccharide and were unable to opsonize C. jejuni isolates lacking glucose, suggesting this should be considered when designing N-glycan-based vaccines to prevent campylobacteriosis.
34726367	7	35	theme	Campylobacter	1291:1303	arg1	colonization					1305:1316	Campylobacter colonization	1291:1316	Campylobacter colonization	1291:1316	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	0	36	theme	N-Glycan	59:66	arg1	Structure					68:76	the Campylobacter jejuni N-Glycan Structure	34:76	the Campylobacter jejuni N-Glycan Structure	34:76	Detecting Glucose Fluctuations in the Campylobacter jejuni N-Glycan Structure.
34726367	7	37	from	antibodies	1247:1256	arg1	colonization					1305:1316	Campylobacter colonization	1291:1316	Campylobacter colonization	1291:1316	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	7	37	from	antibodies	1247:1256	arg1	loss					1329:1332	weight loss	1322:1332	weight loss	1322:1332	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	0	38	theme	jejuni	52:57	arg1	Structure					68:76	the Campylobacter jejuni N-Glycan Structure	34:76	the Campylobacter jejuni N-Glycan Structure	34:76	Detecting Glucose Fluctuations in the Campylobacter jejuni N-Glycan Structure.
34726367	4	39	attach	present	764:770	arg1	sequences					801:809	all available PglI sequences	782:809	all available PglI sequences	782:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	39	attach	present	764:770	arg2	alteration					748:757	an alteration	745:757	an alteration also present in ∼4% of all available PglI sequences	745:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	39	attach	present	764:770	arg2	aspartate					704:712	one aspartate	700:712	one aspartate in the DXDD motif	700:730	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	39	attach	present	764:770	arg1	%					777:777	∼4%	775:777	∼4% of all available PglI sequences	775:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	1	40	theme	human	126:130	arg1	worldwide					148:156	human gastroenteritis worldwide	126:156	human gastroenteritis worldwide	126:156	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	8	41	theme	N-glycan-based	1532:1545	arg1	vaccines					1547:1554	N-glycan-based vaccines	1532:1554	N-glycan-based vaccines	1532:1554	However, the antibodies did not recognize the hexasaccharide and were unable to opsonize C. jejuni isolates lacking glucose, suggesting this should be considered when designing N-glycan-based vaccines to prevent campylobacteriosis.
34726367	4	42	theme	PglI	796:799	arg1	sequences					801:809	all available PglI sequences	782:809	all available PglI sequences	782:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	1	43	theme	gastroenteritis	132:146	arg1	worldwide					148:156	human gastroenteritis worldwide	126:156	human gastroenteritis worldwide	126:156	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	4	44	dep	missing	736:742	arg1	alteration					748:757	an alteration	745:757	an alteration also present in ∼4% of all available PglI sequences	745:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	44	dep	missing	736:742	arg1	aspartate					704:712	one aspartate	700:712	one aspartate in the DXDD motif	700:730	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	2	45	with	unreactive	362:371	arg1	antiserum					400:408	our N-glycan-specific antiserum	378:408	our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	378:523	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	4	46	theme	available	786:794	arg1	sequences					801:809	all available PglI sequences	782:809	all available PglI sequences	782:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	1	47	theme	worldwide	148:156	arg1	jejuni					93:98	Campylobacter jejuni	79:98	Campylobacter jejuni	79:98	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	1	47	theme	worldwide	148:156	arg1	cause					117:121	a significant cause	103:121	a significant cause of human gastroenteritis worldwide	103:156	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	2	48	theme	middle-income	312:324	arg1	countries					326:334	7 low- and middle-income countries	301:334	7 low- and middle-income countries	301:334	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	7	49	theme	corresponding	1264:1276	arg1	reduction					1278:1286	a corresponding reduction	1262:1286	a corresponding reduction in Campylobacter colonization and weight loss	1262:1332	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	7	50	from	reduction	1278:1286	arg1	colonization					1305:1316	Campylobacter colonization	1291:1316	Campylobacter colonization	1291:1316	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	7	50	from	reduction	1278:1286	arg1	loss					1329:1332	weight loss	1322:1332	weight loss	1322:1332	Mouse vaccination with an E. coli strain expressing the full-length heptasaccharide produced N-glycan-specific antibodies and a corresponding reduction in Campylobacter colonization and weight loss following challenge.
34726367	2	51	theme	unreactive	362:371	arg1	isolates					353:360	4 isolates	351:360	4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	351:523	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
34726367	8	52	theme	C.	1444:1445	arg1	isolates					1454:1461	C. jejuni isolates	1444:1461	C. jejuni isolates lacking glucose	1444:1477	However, the antibodies did not recognize the hexasaccharide and were unable to opsonize C. jejuni isolates lacking glucose, suggesting this should be considered when designing N-glycan-based vaccines to prevent campylobacteriosis.
34726367	1	53	theme	different	224:232	arg1	proteins					234:241	at least 80 different proteins	212:241	at least 80 different proteins	212:241	Campylobacter jejuni is a significant cause of human gastroenteritis worldwide, and all strains express an N-glycan that is added to at least 80 different proteins.
34726367	5	54	with	replacement	962:972	arg1	Glu/Ala					979:985	Glu/Ala	979:985	Glu/Ala	979:985	Deleting this residue from an active PglI resulted in a nonfunctional GlcTF when the protein glycosylation system was reconstituted in E. coli, while replacement with Glu/Ala was not deleterious.
34726367	4	55	theme	sequences	801:809	arg1	sequences					801:809	all available PglI sequences	782:809	all available PglI sequences	782:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	4	55	theme	sequences	801:809	arg1	%					777:777	∼4%	775:777	∼4% of all available PglI sequences	775:809	Although all 4 strains encode the PglI glucosyltransferase (GlcTF), one aspartate in the DXDD motif was missing, an alteration also present in ∼4% of all available PglI sequences.
34726367	2	56	theme	heptasaccharide	448:462	arg1	jejuni					441:446	the C. jejuni heptasaccharide	434:462	the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac	434:523	We characterized 98 C. jejuni isolates from infants from 7 low- and middle-income countries and identified 4 isolates unreactive with our N-glycan-specific antiserum that was raised against the C. jejuni heptasaccharide composed of GalNAc-GalNAc-GalNAc(Glc)-GalNAc-GalNAc-diNAcBac.
36303733	8	0	theme	host	1485:1488	arg1	response					1490:1497	the host response	1481:1497	the host response to the infection, vaccines, and antibodies	1481:1540	Conclusion: Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, are factors in the host response to the infection, vaccines, and antibodies.
36303733	4	1	theme	blocking	676:683	arg1	enzymes-swainsonine					694:712	blocking specific enzymes-swainsonine	676:712	blocking specific enzymes-swainsonine	676:712	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	2	2	theme	mass	336:339	arg1	data					354:357	previously published mass spectrometry data	315:357	previously published mass spectrometry data using GNAT, a glycosylation network analysis tool	315:407	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	9	3	from	Heterogeneity	1543:1555	arg1	efficacy					1642:1649	vaccine efficacy	1634:1649	vaccine efficacy	1634:1649	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	9	3	from	Heterogeneity	1543:1555	arg1	reactions					1662:1670	adverse reactions	1654:1670	adverse reactions	1654:1670	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	9	3	from	Heterogeneity	1543:1555	arg1	profile					1573:1579	the N-glycan profile	1560:1579	the N-glycan profile of the spike (S) protein	1560:1604	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	0	4	theme	Spike	75:79	arg1	Glycoprotein					85:96	the Spike (S) Glycoprotein	71:96	the Spike (S) Glycoprotein of SARS-CoV-2	71:110	N-Glycosylation Network Construction and Analysis to Modify Glycans on the Spike (S) Glycoprotein of SARS-CoV-2.
36303733	9	5	theme	potential	1614:1622	arg1	effect					1624:1629	its potential effect	1610:1629	its potential effect on vaccine efficacy or adverse reactions to the vaccines	1610:1686	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	5	6	theme	N-glycan	927:934	arg1	network					949:955	The N-glycan biosynthesis network	923:955	The N-glycan biosynthesis network of SARS-CoV-2 spike protein	923:983	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	2	7	theme	published	326:334	arg1	data					354:357	previously published mass spectrometry data	315:357	previously published mass spectrometry data using GNAT, a glycosylation network analysis tool	315:407	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	8	8	from	Variations	1367:1376	arg1	profile					1400:1406	the final N-glycan profile	1381:1406	the final N-glycan profile of the virus, given its site-specific microheterogeneity,	1381:1464	Conclusion: Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, are factors in the host response to the infection, vaccines, and antibodies.
36303733	1	9	theme	vaccine	220:226	arg1	development					228:238	vaccine development	220:238	vaccine development	220:238	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	3	10	theme	network	433:439	arg1	tool					441:444	the network tool	429:444	the network tool	429:444	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	8	11	theme	virus	1415:1419	arg1	profile					1400:1406	the final N-glycan profile	1381:1406	the final N-glycan profile of the virus, given its site-specific microheterogeneity,	1381:1464	Conclusion: Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, are factors in the host response to the infection, vaccines, and antibodies.
36303733	5	12	theme	enzymatic	1004:1012	arg1	pathway					1014:1020	enzymatic pathway	1004:1020	enzymatic pathway with several intermediate glycans	1004:1054	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	10	13	theme	generated-the	1745:1757	arg1	glycans					1759:1765	generated-the glycans	1745:1765	all the resources we generated-the glycans in the glycoCT xml format	1724:1791	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	0	14	theme	S	82:82	arg1	Glycoprotein					85:96	the Spike (S) Glycoprotein	71:96	the Spike (S) Glycoprotein of SARS-CoV-2	71:110	N-Glycosylation Network Construction and Analysis to Modify Glycans on the Spike (S) Glycoprotein of SARS-CoV-2.
36303733	0	15	from	Glycans	60:66	arg1	Glycoprotein					85:96	the Spike (S) Glycoprotein	71:96	the Spike (S) Glycoprotein of SARS-CoV-2	71:110	N-Glycosylation Network Construction and Analysis to Modify Glycans on the Spike (S) Glycoprotein of SARS-CoV-2.
36303733	3	16	theme	glycosylation	528:540	arg1	machinery					542:550	glycosylation machinery	528:550	glycosylation machinery	528:550	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	5	17	theme	spike	971:975	arg1	protein					977:983	SARS-CoV-2 spike protein	960:983	SARS-CoV-2 spike protein	960:983	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	8	18	from	factors	1470:1476	arg1	response					1490:1497	the host response	1481:1497	the host response to the infection, vaccines, and antibodies	1481:1540	Conclusion: Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, are factors in the host response to the infection, vaccines, and antibodies.
36303733	10	19	dep	resources	1732:1740	arg1	we					1742:1743	we	1742:1743	we	1742:1743	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	9	20	theme	vaccine	1634:1640	arg1	efficacy					1642:1649	vaccine efficacy	1634:1649	vaccine efficacy	1634:1649	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	4	21	theme	glycan	606:611	arg1	pathway					626:632	the glycan biosynthesis pathway	602:632	the glycan biosynthesis pathway	602:632	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	5	22	theme	SARS-CoV-2	960:969	arg1	protein					977:983	SARS-CoV-2 spike protein	960:983	SARS-CoV-2 spike protein	960:983	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	7	23	theme	glycan	1325:1330	arg1	profile					1332:1338	a substantially modified glycan profile	1300:1338	a substantially modified glycan profile of SARS-CoV-2	1300:1352	Blocking specific enzymes resulted in a substantially modified glycan profile of SARS-CoV-2.
36303733	9	24	theme	S	1595:1595	arg1	protein					1598:1604	the spike (S) protein	1584:1604	the spike (S) protein	1584:1604	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	5	25	theme	protein	977:983	arg1	network					949:955	The N-glycan biosynthesis network	923:955	The N-glycan biosynthesis network of SARS-CoV-2 spike protein	923:983	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	6	26	theme	enzymes	1129:1135	arg1	involved-Man-Ia					1157:1171	involved-Man-Ia	1157:1171	involved-Man-Ia	1157:1171	Of the 26 enzymes, the following were involved-Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B3GalT, B4GalT, Man-II, SiaT, ST3GalI, ST3GalVI, and FucT8.
36303733	6	26	theme	enzymes	1129:1135	arg1	MGAT1					1174:1178	MGAT1	1174:1178	MGAT1	1174:1178	Of the 26 enzymes, the following were involved-Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B3GalT, B4GalT, Man-II, SiaT, ST3GalI, ST3GalVI, and FucT8.
36303733	6	26	theme	enzymes	1129:1135	arg1	MGAT5					1195:1199	MGAT5	1195:1199	MGAT5	1195:1199	Of the 26 enzymes, the following were involved-Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B3GalT, B4GalT, Man-II, SiaT, ST3GalI, ST3GalVI, and FucT8.
36303733	6	26	theme	enzymes	1129:1135	arg1	following					1142:1150	the following	1138:1150	the following	1138:1150	Of the 26 enzymes, the following were involved-Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B3GalT, B4GalT, Man-II, SiaT, ST3GalI, ST3GalVI, and FucT8.
36303733	6	26	theme	enzymes	1129:1135	arg1	MGAT2					1181:1185	MGAT2	1181:1185	MGAT2	1181:1185	Of the 26 enzymes, the following were involved-Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B3GalT, B4GalT, Man-II, SiaT, ST3GalI, ST3GalVI, and FucT8.
36303733	6	26	theme	enzymes	1129:1135	arg1	FucT8					1255:1259	FucT8	1255:1259	FucT8	1255:1259	Of the 26 enzymes, the following were involved-Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B3GalT, B4GalT, Man-II, SiaT, ST3GalI, ST3GalVI, and FucT8.
36303733	6	26	theme	enzymes	1129:1135	arg1	MGAT4					1188:1192	MGAT4	1188:1192	MGAT4	1188:1192	Of the 26 enzymes, the following were involved-Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B3GalT, B4GalT, Man-II, SiaT, ST3GalI, ST3GalVI, and FucT8.
36303733	0	27	theme	Network	16:22	arg1	Construction					24:35	N-Glycosylation Network Construction	0:35	N-Glycosylation Network Construction	0:35	N-Glycosylation Network Construction and Analysis to Modify Glycans on the Spike (S) Glycoprotein of SARS-CoV-2.
36303733	2	28	theme	glycosylation	284:296	arg1	network					298:304	the glycosylation network	280:304	the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool	280:407	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	0	29	theme	N-Glycosylation	0:14	arg1	Construction					24:35	N-Glycosylation Network Construction	0:35	N-Glycosylation Network Construction	0:35	N-Glycosylation Network Construction and Analysis to Modify Glycans on the Spike (S) Glycoprotein of SARS-CoV-2.
36303733	9	30	theme	adverse	1654:1660	arg1	reactions					1662:1670	adverse reactions	1654:1670	adverse reactions	1654:1670	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	1	31	theme	spike	171:175	arg1	protein					181:187	the spike (S) protein	167:187	the spike (S) protein of SARS-CoV-2	167:201	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	3	32	theme	machinery	542:550	arg1	pathway					517:523	the pathway	513:523	the pathway of glycosylation machinery based on glycans in the virus spike protein	513:594	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	8	33	theme	N-glycan	1391:1398	arg1	profile					1400:1406	the final N-glycan profile	1381:1406	the final N-glycan profile of the virus, given its site-specific microheterogeneity,	1381:1464	Conclusion: Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, are factors in the host response to the infection, vaccines, and antibodies.
36303733	3	34	theme	tool	441:444	arg1	compilation					414:424	Our compilation	410:424	Our compilation of the network tool	410:444	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	10	35	dep	we	1742:1743	arg1	glycans					1759:1765	generated-the glycans	1745:1765	all the resources we generated-the glycans in the glycoCT xml format	1724:1791	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	10	36	theme	future	1826:1831	arg1	work					1833:1836	future work	1826:1836	future work	1826:1836	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	0	37	theme	SARS-CoV-2	101:110	arg1	Glycoprotein					85:96	the Spike (S) Glycoprotein	71:96	the Spike (S) Glycoprotein of SARS-CoV-2	71:110	N-Glycosylation Network Construction and Analysis to Modify Glycans on the Spike (S) Glycoprotein of SARS-CoV-2.
36303733	8	38	theme	final	1385:1389	arg1	profile					1400:1406	the final N-glycan profile	1381:1406	the final N-glycan profile of the virus, given its site-specific microheterogeneity,	1381:1464	Conclusion: Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, are factors in the host response to the infection, vaccines, and antibodies.
36303733	5	39	theme	biosynthesis	936:947	arg1	network					949:955	The N-glycan biosynthesis network	923:955	The N-glycan biosynthesis network of SARS-CoV-2 spike protein	923:983	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	2	40	theme	analysis	395:402	arg1	GNAT					365:368	GNAT	365:368	GNAT	365:368	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	2	40	theme	analysis	395:402	arg1	tool					404:407	a glycosylation network analysis tool	371:407	a glycosylation network analysis tool	371:407	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	4	41	theme	specific	685:692	arg1	enzymes-swainsonine					694:712	blocking specific enzymes-swainsonine	676:712	blocking specific enzymes-swainsonine	676:712	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	3	42	theme	virus	576:580	arg1	protein					588:594	the virus spike protein	572:594	the virus spike protein	572:594	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	7	43	theme	modified	1316:1323	arg1	profile					1332:1338	a substantially modified glycan profile	1300:1338	a substantially modified glycan profile of SARS-CoV-2	1300:1352	Blocking specific enzymes resulted in a substantially modified glycan profile of SARS-CoV-2.
36303733	2	44	theme	network	387:393	arg1	GNAT					365:368	GNAT	365:368	GNAT	365:368	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	2	44	theme	network	387:393	arg1	tool					404:407	a glycosylation network analysis tool	371:407	a glycosylation network analysis tool	371:407	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	9	45	from	effect	1624:1629	arg1	efficacy					1642:1649	vaccine efficacy	1634:1649	vaccine efficacy	1634:1649	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	9	45	from	effect	1624:1629	arg1	reactions					1662:1670	adverse reactions	1654:1670	adverse reactions	1654:1670	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	9	45	from	effect	1624:1629	arg1	profile					1573:1579	the N-glycan profile	1560:1579	the N-glycan profile of the spike (S) protein	1560:1604	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	3	46	contain	had	446:448	arg1	compilation					414:424	Our compilation	410:424	Our compilation of the network tool	410:444	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	3	46	contain	had	446:448	arg2	enzymes					489:495	26 glycosyltransferase and glucosidase enzymes	450:495	enzymes	489:495	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	3	46	contain	had	446:448	arg2	glycosyltransferase					453:471	26 glycosyltransferase and glucosidase enzymes	450:495	glycosyltransferase	453:471	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	1	47	dep	spike	171:175	arg1	S					178:178	S	178:178	S	178:178	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	8	48	theme	site-specific	1432:1444	arg1	microheterogeneity					1446:1463	its site-specific microheterogeneity	1428:1463	its site-specific microheterogeneity	1428:1463	Conclusion: Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, are factors in the host response to the infection, vaccines, and antibodies.
36303733	1	49	theme	protein	181:187	arg1	composition					152:162	composition	152:162	composition	152:162	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	1	49	theme	protein	181:187	arg1	pertinent					207:215	pertinent	207:215	pertinent	207:215	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	1	49	theme	protein	181:187	arg1	structure					138:146	N-glycan structure	129:146	N-glycan structure	129:146	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	10	50	theme	biosynthesis	1801:1812	arg1	network					1814:1820	the biosynthesis network	1797:1820	the biosynthesis network for future work	1797:1836	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	9	51	theme	spike	1588:1592	arg1	protein					1598:1604	the spike (S) protein	1584:1604	the spike (S) protein	1584:1604	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	4	52	theme	enzymes-swainsonine	694:712	arg1	effect					666:671	the effect	662:671	the effect of blocking specific enzymes-swainsonine or deoxynojirimycin	662:732	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	5	53	with	pathway	1014:1020	arg1	glycans					1048:1054	several intermediate glycans	1027:1054	several intermediate glycans	1027:1054	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	4	54	theme	biosynthesis	854:865	arg1	network					867:873	the biosynthesis network	850:873	the biosynthesis network	850:873	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	3	55	theme	glucosidase	477:487	arg1	enzymes					489:495	26 glycosyltransferase and glucosidase enzymes	450:495	enzymes	489:495	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	10	56	theme	xml	1782:1784	arg1	format					1786:1791	the glycoCT xml format	1770:1791	the glycoCT xml format	1770:1791	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	5	57	theme	mass	1091:1094	arg1	studies					1110:1116	mass spectrometric studies	1091:1116	mass spectrometric studies	1091:1116	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	5	58	theme	intermediate	1035:1046	arg1	glycans					1048:1054	several intermediate glycans	1027:1054	several intermediate glycans	1027:1054	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	3	59	theme	spike	582:586	arg1	protein					588:594	the virus spike protein	572:594	the virus spike protein	572:594	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	4	60	theme	deoxynojirimycin	717:732	arg1	effect					666:671	the effect	662:671	the effect of blocking specific enzymes-swainsonine or deoxynojirimycin	662:732	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	9	61	theme	N-glycan	1564:1571	arg1	profile					1573:1579	the N-glycan profile	1560:1579	the N-glycan profile of the spike (S) protein	1560:1604	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	5	62	theme	several	1027:1033	arg1	glycans					1048:1054	several intermediate glycans	1027:1054	several intermediate glycans	1027:1054	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	5	63	theme	spectrometric	1096:1108	arg1	studies					1110:1116	mass spectrometric studies	1091:1116	mass spectrometric studies	1091:1116	Results: The N-glycan biosynthesis network of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies.
36303733	10	64	from	resources	1732:1740	arg1	format					1786:1791	the glycoCT xml format	1770:1791	the glycoCT xml format	1770:1791	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	1	65	theme	N-glycan	129:136	arg1	pertinent					207:215	pertinent	207:215	pertinent	207:215	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	1	65	theme	N-glycan	129:136	arg1	structure					138:146	N-glycan structure	129:146	N-glycan structure	129:146	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	1	66	theme	SARS-CoV-2	192:201	arg1	protein					181:187	the spike (S) protein	167:187	the spike (S) protein of SARS-CoV-2	167:201	Background: The N-glycan structure and composition of the spike (S) protein of SARS-CoV-2 are pertinent to vaccine development and efficacy.
36303733	10	67	from	network	1814:1820	arg1	format					1786:1791	the glycoCT xml format	1770:1791	the glycoCT xml format	1770:1791	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	2	68	theme	glycosylation	373:385	arg1	GNAT					365:368	GNAT	365:368	GNAT	365:368	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	2	68	theme	glycosylation	373:385	arg1	tool					404:407	a glycosylation network analysis tool	371:407	a glycosylation network analysis tool	371:407	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	9	69	theme	protein	1598:1604	arg1	profile					1573:1579	the N-glycan profile	1560:1579	the N-glycan profile of the spike (S) protein	1560:1604	Heterogeneity in the N-glycan profile of the spike (S) protein and its potential effect on vaccine efficacy or adverse reactions to the vaccines remain unexplored.
36303733	4	70	theme	biosynthesis	613:624	arg1	pathway					626:632	the glycan biosynthesis pathway	602:632	the glycan biosynthesis pathway	602:632	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	4	71	dep	alpha-1,6-fucosyltransferase-to	792:822	arg1	see					824:826	see	824:826	see how they would affect the biosynthesis network and the glycans that were synthesized	824:911	Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes-swainsonine or deoxynojirimycin for blocking mannosidase-II and indolizidine for blocking alpha-1,6-fucosyltransferase-to see how they would affect the biosynthesis network and the glycans that were synthesized.
36303733	3	72	from	glycans	561:567	arg1	protein					588:594	the virus spike protein	572:594	the virus spike protein	572:594	Our compilation of the network tool had 26 glycosyltransferase and glucosidase enzymes and could infer the pathway of glycosylation machinery based on glycans in the virus spike protein.
36303733	7	73	theme	SARS-CoV-2	1343:1352	arg1	profile					1332:1338	a substantially modified glycan profile	1300:1338	a substantially modified glycan profile of SARS-CoV-2	1300:1352	Blocking specific enzymes resulted in a substantially modified glycan profile of SARS-CoV-2.
36303733	10	74	theme	glycoCT	1774:1780	arg1	format					1786:1791	the glycoCT xml format	1770:1791	the glycoCT xml format	1770:1791	Here, we provide all the resources we generated-the glycans in the glycoCT xml format and the biosynthesis network for future work.
36303733	2	75	theme	spectrometry	341:352	arg1	data					354:357	previously published mass spectrometry data	315:357	previously published mass spectrometry data using GNAT, a glycosylation network analysis tool	315:407	Methods: We reconstructed the glycosylation network based on previously published mass spectrometry data using GNAT, a glycosylation network analysis tool.
36303733	7	76	theme	specific	1271:1278	arg1	enzymes					1280:1286	specific enzymes	1271:1286	specific enzymes	1271:1286	Blocking specific enzymes resulted in a substantially modified glycan profile of SARS-CoV-2.
34241972	0	0	theme	complement	78:87	arg1	C6					98:99	C6	98:99	C6	98:99	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	0	theme	complement	78:87	arg1	proteins					89:96	the complement proteins C6 and C7	74:106	the complement proteins C6 and C7	74:106	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	0	theme	complement	78:87	arg1	C7					105:106	C7	105:106	C7	105:106	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	1	from	differences	17:27	arg1	structures					36:45	structures	36:45	structures	36:45	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	1	from	differences	17:27	arg1	profiles					62:69	proteoform profiles	51:69	proteoform profiles	51:69	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	9	2	dep	structure	1266:1274	arg1	the					1262:1264	the	1262:1264	the	1262:1264	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	6	3	theme	glycosylation	922:934	arg1	data					936:939	structural and glycosylation data	907:939	data	936:939	We compare this data with structural and glycosylation data for human serum C6.
34241972	5	4	theme	native	702:707	arg1	MS					709:710	native MS	702:710	native MS	702:710	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	7	5	theme	compact	1016:1022	arg1	conformation					1024:1035	a compact conformation	1014:1035	a compact conformation in solution	1014:1047	The new structural model for C7 shows that it adopts a compact conformation in solution.
34241972	2	6	dep	components	276:285	arg1	C8					300:301	C8	300:301	C8	300:301	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	6	dep	components	276:285	arg1	C9					308:309	C9	308:309	C9	308:309	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	6	dep	components	276:285	arg1	C7					296:297	C7	296:297	C7	296:297	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	6	dep	components	276:285	arg1	C6					292:293	C6	292:293	C6	292:293	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	6	dep	components	276:285	arg1	components					276:285	terminal complement components	256:285	terminal complement components (C5, C6, C7, C8, and C9)	256:310	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	6	7	theme	serum	951:955	arg1	C6					957:958	human serum C6	945:958	human serum C6	945:958	We compare this data with structural and glycosylation data for human serum C6.
34241972	0	8	from	Similarities	0:11	arg1	structures					36:45	structures	36:45	structures	36:45	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	8	from	Similarities	0:11	arg1	profiles					62:69	proteoform profiles	51:69	proteoform profiles	51:69	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	5	9	theme	integrative	651:661	arg1	approach					683:690	an integrative structural MS-based approach	648:690	an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling	648:794	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	0	10	dep	structures	36:45	arg1	the					32:34	the	32:34	the	32:34	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	6	11	theme	structural	907:916	arg1	data					936:939	structural and glycosylation data	907:939	data	936:939	We compare this data with structural and glycosylation data for human serum C6.
34241972	0	12	theme	proteins	89:96	arg1	structures					36:45	structures	36:45	structures	36:45	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	12	theme	proteins	89:96	arg1	profiles					62:69	proteoform profiles	51:69	proteoform profiles	51:69	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	4	13	dep	proteins	495:502	arg1	C6					511:512	C6	511:512	C6	511:512	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	4	13	dep	proteins	495:502	arg1	C7					504:505	C7	504:505	C7	504:505	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	4	13	dep	proteins	495:502	arg1	proteins					495:502	The complement proteins	480:502	The complement proteins C7 and C6	480:512	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	5	14	used	used	643:646	arg2	we					640:641	we	640:641	we	640:641	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	2	15	theme	components	276:285	arg1	array					247:251	an array	244:251	an array of terminal complement components (C5, C6, C7, C8, and C9)	244:310	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	5	16	theme	human	857:861	arg1	C7					877:878	human serum soluble C7	857:878	human serum soluble C7	857:878	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	4	17	theme	C-mannosylation	611:625	arg1	sites					627:631	C-mannosylation sites	611:631	C-mannosylation sites	611:631	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	9	18	theme	assembly	1368:1375	arg1	understanding					1347:1359	our understanding	1343:1359	our understanding of MAC assembly	1343:1375	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	8	19	theme	many	1075:1078	arg1	similarities					1080:1091	many similarities	1075:1091	many similarities	1075:1091	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	3	20	theme	C7	455:456	arg1	structure					430:438	the structure	426:438	the structure of the soluble C7	426:456	Although much information about MAC assembly is available, the structure of the soluble C7 has remained elusive.
34241972	9	21	theme	puzzle	1333:1338	arg1	piece					1320:1324	an essential piece	1307:1324	an essential piece of the puzzle in our understanding of MAC assembly	1307:1375	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	2	22	theme	membrane	336:343	arg1	complex					352:358	the membrane attack complex	332:358	the membrane attack complex (MAC)	332:364	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	22	theme	membrane	336:343	arg1	MAC					361:363	MAC	361:363	MAC	361:363	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	5	23	theme	structural	663:672	arg1	approach					683:690	an integrative structural MS-based approach	648:690	an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling	648:794	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	2	24	theme	terminal	256:263	arg1	components					276:285	terminal complement components	256:285	terminal complement components (C5, C6, C7, C8, and C9)	256:310	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	24	theme	terminal	256:263	arg1	C8					300:301	C8	300:301	C8	300:301	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	24	theme	terminal	256:263	arg1	C7					296:297	C7	296:297	C7	296:297	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	24	theme	terminal	256:263	arg1	C6					292:293	C6	292:293	C6	292:293	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	24	theme	terminal	256:263	arg1	C9					308:309	C9	308:309	C9	308:309	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	3	25	theme	much	376:379	arg1	information					381:391	much information	376:391	much information about MAC assembly	376:410	Although much information about MAC assembly is available, the structure of the soluble C7 has remained elusive.
34241972	9	26	from	piece	1320:1324	arg1	understanding					1347:1359	our understanding	1343:1359	our understanding of MAC assembly	1343:1375	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	5	27	theme	serum	863:867	arg1	C7					877:878	human serum soluble C7	857:878	human serum soluble C7	857:878	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	1	28	theme	defence	162:168	arg1	line					154:157	a first line	146:157	a first line of defence against pathogens	146:186	The human complement system provides a first line of defence against pathogens.
34241972	5	29	theme	in-gel	738:743	arg1	IGX-MS					763:768	IGX-MS	763:768	IGX-MS	763:768	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	5	29	theme	in-gel	738:743	arg1	MS					759:760	in-gel cross-linking MS	738:760	in-gel cross-linking MS (IGX-MS)	738:769	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	8	30	theme	N-linked	1128:1135	arg1	glycosylation					1137:1149	N-linked glycosylation	1128:1149	N-linked glycosylation	1128:1149	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	9	31	theme	essential	1310:1318	arg1	piece					1320:1324	an essential piece	1307:1324	an essential piece of the puzzle in our understanding of MAC assembly	1307:1375	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	5	32	theme	soluble	869:875	arg1	C7					877:878	human serum soluble C7	857:878	human serum soluble C7	857:878	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	4	33	theme	disulphide	587:596	arg1	bridges					598:604	disulphide bridges	587:604	disulphide bridges	587:604	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	5	34	theme	cross-linking	745:757	arg1	IGX-MS					763:768	IGX-MS	763:768	IGX-MS	763:768	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	5	34	theme	cross-linking	745:757	arg1	MS					759:760	in-gel cross-linking MS	738:760	in-gel cross-linking MS (IGX-MS)	738:769	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	9	35	theme	MAC	1364:1366	arg1	assembly					1368:1375	MAC assembly	1364:1375	MAC assembly	1364:1375	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	8	36	theme	composition	1192:1202	arg1	terms					1163:1167	terms	1163:1167	terms of location and glycan composition	1163:1202	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	5	37	theme	C7	877:878	arg1	features					819:826	structural features	808:826	structural features	808:826	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	5	37	theme	C7	877:878	arg1	glycosylation					839:851	glycosylation	839:851	glycosylation	839:851	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	3	38	theme	MAC	399:401	arg1	assembly					403:410	MAC assembly	399:410	MAC assembly	399:410	Although much information about MAC assembly is available, the structure of the soluble C7 has remained elusive.
34241972	9	39	theme	new	1245:1247	arg1	insight					1249:1255	valuable new insight	1236:1255	valuable new insight into the structure and proteoforms of C7	1236:1296	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	2	40	theme	complement	265:274	arg1	components					276:285	terminal complement components	256:285	terminal complement components (C5, C6, C7, C8, and C9)	256:310	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	40	theme	complement	265:274	arg1	C8					300:301	C8	300:301	C8	300:301	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	40	theme	complement	265:274	arg1	C7					296:297	C7	296:297	C7	296:297	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	40	theme	complement	265:274	arg1	C6					292:293	C6	292:293	C6	292:293	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	40	theme	complement	265:274	arg1	C9					308:309	C9	308:309	C9	308:309	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	1	41	theme	first	148:152	arg1	line					154:157	a first line	146:157	a first line of defence against pathogens	146:186	The human complement system provides a first line of defence against pathogens.
34241972	8	42	theme	distinct	1111:1118	arg1	O-					1120:1121	distinct O-	1111:1121	distinct O-	1111:1121	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	4	43	theme	complement	484:493	arg1	C6					511:512	C6	511:512	C6	511:512	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	4	43	theme	complement	484:493	arg1	C7					504:505	C7	504:505	C7	504:505	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	4	43	theme	complement	484:493	arg1	proteins					495:502	The complement proteins	480:502	The complement proteins C7 and C6	480:512	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	7	44	theme	structural	969:978	arg1	model					980:984	The new structural model	961:984	The new structural model for C7	961:991	The new structural model for C7 shows that it adopts a compact conformation in solution.
34241972	8	45	theme	location	1172:1179	arg1	terms					1163:1167	terms	1163:1167	terms of location and glycan composition	1163:1202	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	4	46	theme	conserved	568:576	arg1	domains					578:584	several conserved domains	560:584	several conserved domains	560:584	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	5	47	theme	structural	775:784	arg1	modelling					786:794	structural modelling	775:794	structural modelling	775:794	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	8	48	gly	glycosylation	1137:1149	arg1	terms					1163:1167	terms	1163:1167	terms of location and glycan composition	1163:1202	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	2	49	theme	sequential	221:230	arg1	assembly					232:239	a well-orchestrated sequential assembly	201:239	a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9)	201:310	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	50	theme	attack	345:350	arg1	complex					352:358	the membrane attack complex	332:358	the membrane attack complex (MAC)	332:364	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	2	50	theme	attack	345:350	arg1	MAC					361:363	MAC	361:363	MAC	361:363	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	0	51	theme	proteoform	51:60	arg1	profiles					62:69	proteoform profiles	51:69	proteoform profiles	51:69	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	9	52	theme	valuable	1236:1243	arg1	insight					1249:1255	valuable new insight	1236:1255	valuable new insight into the structure and proteoforms of C7	1236:1296	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	2	53	theme	well-orchestrated	203:219	arg1	assembly					232:239	a well-orchestrated sequential assembly	201:239	a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9)	201:310	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	8	54	theme	glycan	1185:1190	arg1	composition					1192:1202	glycan composition	1185:1202	glycan composition	1185:1202	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	7	55	from	conformation	1024:1035	arg1	solution					1040:1047	solution	1040:1047	solution	1040:1047	The new structural model for C7 shows that it adopts a compact conformation in solution.
34241972	7	56	theme	new	965:967	arg1	model					980:984	The new structural model	961:984	The new structural model for C7	961:991	The new structural model for C7 shows that it adopts a compact conformation in solution.
34241972	8	57	link	N-linked	1128:1135	arg1	glycosylation					1137:1149	N-linked glycosylation	1128:1149	N-linked glycosylation	1128:1149	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	8	58	dep	O-	1120:1121	arg1	patterns					1151:1158	patterns	1151:1158	patterns	1151:1158	Although C6 and C7 share many similarities, our data reveals distinct O-, and N-linked glycosylation patterns in terms of location and glycan composition.
34241972	4	59	gly	C-mannosylation	611:625	arg2	sites					627:631	C-mannosylation sites	611:631	C-mannosylation sites	611:631	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	9	60	from	understanding	1347:1359	arg1	piece					1320:1324	an essential piece	1307:1324	an essential piece of the puzzle in our understanding of MAC assembly	1307:1375	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	1	61	theme	human	113:117	arg1	system					130:135	The human complement system	109:135	The human complement system	109:135	The human complement system provides a first line of defence against pathogens.
34241972	4	62	theme	high	525:528	arg1	homology					539:546	very high sequence homology	520:546	very high sequence homology	520:546	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	0	63	dep	proteins	89:96	arg1	C6					98:99	C6	98:99	C6	98:99	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	63	dep	proteins	89:96	arg1	proteins					89:96	the complement proteins C6 and C7	74:106	the complement proteins C6 and C7	74:106	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	0	63	dep	proteins	89:96	arg1	C7					105:106	C7	105:106	C7	105:106	Similarities and differences in the structures and proteoform profiles of the complement proteins C6 and C7.
34241972	2	64	theme	array	247:251	arg1	assembly					232:239	a well-orchestrated sequential assembly	201:239	a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9)	201:310	It requires a well-orchestrated sequential assembly of an array of terminal complement components (C5, C6, C7, C8, and C9), ultimately forming the membrane attack complex (MAC).
34241972	9	65	from	puzzle	1333:1338	arg1	understanding					1347:1359	our understanding	1343:1359	our understanding of MAC assembly	1343:1375	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	1	66	theme	complement	119:128	arg1	system					130:135	The human complement system	109:135	The human complement system	109:135	The human complement system provides a first line of defence against pathogens.
34241972	6	67	theme	human	945:949	arg1	C6					957:958	human serum C6	945:958	human serum C6	945:958	We compare this data with structural and glycosylation data for human serum C6.
34241972	5	68	theme	MS-based	674:681	arg1	approach					683:690	an integrative structural MS-based approach	648:690	an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling	648:794	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	4	69	theme	several	560:566	arg1	domains					578:584	several conserved domains	560:584	several conserved domains	560:584	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
34241972	5	70	theme	structural	808:817	arg1	features					819:826	structural features	808:826	structural features	808:826	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	5	70	theme	structural	808:817	arg1	glycosylation					839:851	glycosylation	839:851	glycosylation	839:851	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	9	71	theme	C7	1295:1296	arg1	proteoforms					1280:1290	proteoforms	1280:1290	proteoforms	1280:1290	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	9	71	theme	C7	1295:1296	arg1	structure					1266:1274	structure	1266:1274	structure	1266:1274	Cumulatively, our data provide valuable new insight into the structure and proteoforms of C7, solving an essential piece of the puzzle in our understanding of MAC assembly.
34241972	5	72	theme	glycopeptide-centric	713:732	arg1	MS					734:735	glycopeptide-centric MS	713:735	glycopeptide-centric MS	713:735	Here, we used an integrative structural MS-based approach combining native MS, glycopeptide-centric MS, in-gel cross-linking MS (IGX-MS) and structural modelling to describe structural features, including glycosylation, of human serum soluble C7.
34241972	3	73	theme	soluble	447:453	arg1	C7					455:456	the soluble C7	443:456	the soluble C7	443:456	Although much information about MAC assembly is available, the structure of the soluble C7 has remained elusive.
34241972	4	74	theme	sequence	530:537	arg1	homology					539:546	very high sequence homology	520:546	very high sequence homology	520:546	The complement proteins C7 and C6 share very high sequence homology and exhibit several conserved domains, disulphide bridges, and C-mannosylation sites.
33829797	0	0	theme	Solid-Phase	95:105	arg1	Permethylation					107:120	Optimized Solid-Phase Permethylation	85:120	Optimized Solid-Phase Permethylation Using Mass Spectrometry	85:144	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	4	1	theme	optimized	834:842	arg1	workflow					878:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	6	2	with	method	1326:1331	arg1	purposes					1353:1360	their research purposes	1338:1360	their research purposes	1338:1360	Based on different standard procedures across laboratories, this study provides the reference for analysts to select an appropriate N-glycan preparation method with their research purposes.
33829797	0	3	theme	Optimized	85:93	arg1	Permethylation					107:120	Optimized Solid-Phase Permethylation	85:120	Optimized Solid-Phase Permethylation Using Mass Spectrometry	85:144	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	3	4	theme	trypsin	622:628	arg1	digestion					630:638	trypsin digestion	622:638	trypsin digestion followed by reversed phase-based solid-phase extraction	622:694	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	5	5	used	utilized	1092:1099	arg2	samples					1038:1044	The N-glycan samples	1025:1044	The N-glycan samples released from trastuzumab and adalimumab	1025:1085	The N-glycan samples released from trastuzumab and adalimumab were utilized to test OSPP to obtain their N-glycan profiles using mass spectrometry.
33829797	3	6	theme	phase-based	661:671	arg1	extraction					685:694	reversed phase-based solid-phase extraction	652:694	reversed phase-based solid-phase extraction	652:694	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	0	7	theme	Permethylation	107:120	arg1	Development					70:80	Development	70:80	Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry	70:144	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	0	7	theme	Permethylation	107:120	arg1	Approaches					55:64	Different N-glycan Preparation Approaches	24:64	Different N-glycan Preparation Approaches	24:64	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	5	8	theme	N-glycan	1130:1137	arg1	profiles					1139:1146	their N-glycan profiles	1124:1146	their N-glycan profiles using mass spectrometry	1124:1170	The N-glycan samples released from trastuzumab and adalimumab were utilized to test OSPP to obtain their N-glycan profiles using mass spectrometry.
33829797	3	9	theme	solid-phase	673:683	arg1	extraction					685:694	reversed phase-based solid-phase extraction	652:694	reversed phase-based solid-phase extraction	652:694	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	5	10	attach	released	1046:1053	arg2	samples					1038:1044	The N-glycan samples	1025:1044	The N-glycan samples released from trastuzumab and adalimumab	1025:1085	The N-glycan samples released from trastuzumab and adalimumab were utilized to test OSPP to obtain their N-glycan profiles using mass spectrometry.
33829797	5	10	attach	released	1046:1053	arg1	trastuzumab					1060:1070	trastuzumab	1060:1070	trastuzumab	1060:1070	The N-glycan samples released from trastuzumab and adalimumab were utilized to test OSPP to obtain their N-glycan profiles using mass spectrometry.
33829797	5	10	attach	released	1046:1053	arg1	adalimumab					1076:1085	adalimumab	1076:1085	adalimumab	1076:1085	The N-glycan samples released from trastuzumab and adalimumab were utilized to test OSPP to obtain their N-glycan profiles using mass spectrometry.
33829797	4	11	theme	comparative	809:819	arg1	analysis					821:828	the comparative analysis	805:828	the comparative analysis	805:828	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	1	12	theme	structural	210:219	arg1	micro-					221:226	structural micro-	210:226	structural micro-	210:226	Protein N-glycosylation characterization is challenging due to structural micro- and macro-heterogeneity.
33829797	0	13	theme	Mass	128:131	arg1	Spectrometry					133:144	Mass Spectrometry	128:144	Mass Spectrometry	128:144	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	3	14	theme	different	490:498	arg1	amination					774:782	reductive amination	764:782	reductive amination	764:782	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	14	theme	different	490:498	arg1	digestion					630:638	trypsin digestion	622:638	trypsin digestion followed by reversed phase-based solid-phase extraction	622:694	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	14	theme	different	490:498	arg1	strategies					522:531	the different N-glycan purification strategies	486:531	the different N-glycan purification strategies	486:531	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	14	theme	different	490:498	arg1	reduction					789:797	reduction	789:797	reduction	789:797	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	14	theme	different	490:498	arg1	precipitation					603:615	de-N-glycosylated protein precipitation	577:615	de-N-glycosylated protein precipitation	577:615	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	14	theme	different	490:498	arg1	permethylation					748:761	solid-phase permethylation	736:761	solid-phase permethylation	736:761	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	14	theme	different	490:498	arg1	approaches					716:725	derivatization approaches	701:725	derivatization approaches	701:725	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	14	theme	different	490:498	arg1	preparation					564:574	filter-aided sample preparation	544:574	filter-aided sample preparation	544:574	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	15	theme	reversed	652:659	arg1	extraction					685:694	reversed phase-based solid-phase extraction	652:694	reversed phase-based solid-phase extraction	652:694	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	6	16	theme	research	1344:1351	arg1	purposes					1353:1360	their research purposes	1338:1360	their research purposes	1338:1360	Based on different standard procedures across laboratories, this study provides the reference for analysts to select an appropriate N-glycan preparation method with their research purposes.
33829797	2	17	theme	spectrometric	391:403	arg1	analysis					405:412	mass spectrometric analysis	386:412	mass spectrometric analysis	386:412	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	3	18	theme	purification	509:520	arg1	amination					774:782	reductive amination	764:782	reductive amination	764:782	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	18	theme	purification	509:520	arg1	digestion					630:638	trypsin digestion	622:638	trypsin digestion followed by reversed phase-based solid-phase extraction	622:694	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	18	theme	purification	509:520	arg1	strategies					522:531	the different N-glycan purification strategies	486:531	the different N-glycan purification strategies	486:531	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	18	theme	purification	509:520	arg1	reduction					789:797	reduction	789:797	reduction	789:797	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	18	theme	purification	509:520	arg1	precipitation					603:615	de-N-glycosylated protein precipitation	577:615	de-N-glycosylated protein precipitation	577:615	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	18	theme	purification	509:520	arg1	permethylation					748:761	solid-phase permethylation	736:761	solid-phase permethylation	736:761	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	18	theme	purification	509:520	arg1	approaches					716:725	derivatization approaches	701:725	derivatization approaches	701:725	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	18	theme	purification	509:520	arg1	preparation					564:574	filter-aided sample preparation	544:574	filter-aided sample preparation	544:574	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	0	19	theme	Comparative	0:10	arg1	Analysis					12:19	Comparative Analysis	0:19	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.	0:145	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	2	20	theme	mass	386:389	arg1	analysis					405:412	mass spectrometric analysis	386:412	mass spectrometric analysis	386:412	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	4	21	theme	mass	905:908	arg1	N-glycomics					924:934	mass spectrometric N-glycomics	905:934	mass spectrometric N-glycomics	905:934	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	0	22	theme	Different	24:32	arg1	Approaches					55:64	Different N-glycan Preparation Approaches	24:64	Different N-glycan Preparation Approaches	24:64	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	3	23	theme	derivatization	701:714	arg1	approaches					716:725	derivatization approaches	701:725	derivatization approaches	701:725	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	24	gly	de-N-glycosylated	577:593	arg1	precipitation					603:615	de-N-glycosylated protein precipitation	577:615	de-N-glycosylated protein precipitation	577:615	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	0	25	theme	Preparation	43:53	arg1	Approaches					55:64	Different N-glycan Preparation Approaches	24:64	Different N-glycan Preparation Approaches	24:64	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	2	26	theme	systematic	415:424	arg1	evaluation					426:435	systematic evaluation	415:435	systematic evaluation	415:435	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	6	27	theme	N-glycan	1305:1312	arg1	method					1326:1331	an appropriate N-glycan preparation method	1290:1331	an appropriate N-glycan preparation method with their research purposes	1290:1360	Based on different standard procedures across laboratories, this study provides the reference for analysts to select an appropriate N-glycan preparation method with their research purposes.
33829797	4	28	theme	N-glycan	969:976	arg1	compositions					978:989	N-glycan compositions	969:989	N-glycan compositions	969:989	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	3	29	theme	filter-aided	544:555	arg1	preparation					564:574	filter-aided sample preparation	544:574	filter-aided sample preparation	544:574	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	0	30	theme	N-glycan	34:41	arg1	Approaches					55:64	Different N-glycan Preparation Approaches	24:64	Different N-glycan Preparation Approaches	24:64	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	3	31	theme	N-glycan	500:507	arg1	amination					774:782	reductive amination	764:782	reductive amination	764:782	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	31	theme	N-glycan	500:507	arg1	digestion					630:638	trypsin digestion	622:638	trypsin digestion followed by reversed phase-based solid-phase extraction	622:694	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	31	theme	N-glycan	500:507	arg1	strategies					522:531	the different N-glycan purification strategies	486:531	the different N-glycan purification strategies	486:531	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	31	theme	N-glycan	500:507	arg1	reduction					789:797	reduction	789:797	reduction	789:797	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	31	theme	N-glycan	500:507	arg1	precipitation					603:615	de-N-glycosylated protein precipitation	577:615	de-N-glycosylated protein precipitation	577:615	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	31	theme	N-glycan	500:507	arg1	permethylation					748:761	solid-phase permethylation	736:761	solid-phase permethylation	736:761	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	31	theme	N-glycan	500:507	arg1	approaches					716:725	derivatization approaches	701:725	derivatization approaches	701:725	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	31	theme	N-glycan	500:507	arg1	preparation					564:574	filter-aided sample preparation	544:574	filter-aided sample preparation	544:574	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	32	theme	sample	557:562	arg1	preparation					564:574	filter-aided sample preparation	544:574	filter-aided sample preparation	544:574	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	5	33	theme	N-glycan	1029:1036	arg1	samples					1038:1044	The N-glycan samples	1025:1044	The N-glycan samples released from trastuzumab and adalimumab	1025:1085	The N-glycan samples released from trastuzumab and adalimumab were utilized to test OSPP to obtain their N-glycan profiles using mass spectrometry.
33829797	6	34	theme	appropriate	1293:1303	arg1	method					1326:1331	an appropriate N-glycan preparation method	1290:1331	an appropriate N-glycan preparation method with their research purposes	1290:1360	Based on different standard procedures across laboratories, this study provides the reference for analysts to select an appropriate N-glycan preparation method with their research purposes.
33829797	4	35	theme	permethylation	856:869	arg1	workflow					878:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	0	36	theme	Approaches	55:64	arg1	Analysis					12:19	Comparative Analysis	0:19	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.	0:145	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	4	37	theme	high	995:998	arg1	yields					1000:1005	high yields	995:1005	high yields	995:1005	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	2	38	theme	N-glycan	270:277	arg1	derivatization					330:343	derivatization	330:343	derivatization	330:343	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	2	38	theme	N-glycan	270:277	arg1	strategies					291:300	various N-glycan preparation strategies	262:300	various N-glycan preparation strategies	262:300	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	2	38	theme	N-glycan	270:277	arg1	purification					313:324	purification	313:324	purification	313:324	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	2	39	theme	preparation	279:289	arg1	derivatization					330:343	derivatization	330:343	derivatization	330:343	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	2	39	theme	preparation	279:289	arg1	strategies					291:300	various N-glycan preparation strategies	262:300	various N-glycan preparation strategies	262:300	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	2	39	theme	preparation	279:289	arg1	purification					313:324	purification	313:324	purification	313:324	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	1	40	theme	Protein	147:153	arg1	characterization					171:186	Protein N-glycosylation characterization	147:186	Protein N-glycosylation characterization	147:186	Protein N-glycosylation characterization is challenging due to structural micro- and macro-heterogeneity.
33829797	4	41	theme	OSPP	872:875	arg1	workflow					878:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	2	42	theme	various	262:268	arg1	derivatization					330:343	derivatization	330:343	derivatization	330:343	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	2	42	theme	various	262:268	arg1	strategies					291:300	various N-glycan preparation strategies	262:300	various N-glycan preparation strategies	262:300	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	2	42	theme	various	262:268	arg1	purification					313:324	purification	313:324	purification	313:324	Although various N-glycan preparation strategies, including purification and derivatization, have been previously developed prior to mass spectrometric analysis, systematic evaluation still needs to be performed.
33829797	5	43	theme	mass	1154:1157	arg1	spectrometry					1159:1170	mass spectrometry	1154:1170	mass spectrometry	1154:1170	The N-glycan samples released from trastuzumab and adalimumab were utilized to test OSPP to obtain their N-glycan profiles using mass spectrometry.
33829797	6	44	theme	standard	1192:1199	arg1	procedures					1201:1210	different standard procedures	1182:1210	different standard procedures across laboratories	1182:1230	Based on different standard procedures across laboratories, this study provides the reference for analysts to select an appropriate N-glycan preparation method with their research purposes.
33829797	1	45	theme	N-glycosylation	155:169	arg1	characterization					171:186	Protein N-glycosylation characterization	147:186	Protein N-glycosylation characterization	147:186	Protein N-glycosylation characterization is challenging due to structural micro- and macro-heterogeneity.
33829797	4	46	theme	spectrometric	910:922	arg1	N-glycomics					924:934	mass spectrometric N-glycomics	905:934	mass spectrometric N-glycomics	905:934	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	3	47	theme	reductive	764:772	arg1	amination					774:782	reductive amination	764:782	reductive amination	764:782	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	48	theme	protein	595:601	arg1	precipitation					603:615	de-N-glycosylated protein precipitation	577:615	de-N-glycosylated protein precipitation	577:615	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	6	49	theme	preparation	1314:1324	arg1	method					1326:1331	an appropriate N-glycan preparation method	1290:1331	an appropriate N-glycan preparation method with their research purposes	1290:1360	Based on different standard procedures across laboratories, this study provides the reference for analysts to select an appropriate N-glycan preparation method with their research purposes.
33829797	3	50	theme	de-N-glycosylated	577:593	arg1	precipitation					603:615	de-N-glycosylated protein precipitation	577:615	de-N-glycosylated protein precipitation	577:615	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	3	51	theme	solid-phase	736:746	arg1	permethylation					748:761	solid-phase permethylation	736:761	solid-phase permethylation	736:761	This study compared the different N-glycan purification strategies, including filter-aided sample preparation, de-N-glycosylated protein precipitation, and trypsin digestion followed by reversed phase-based solid-phase extraction, and derivatization approaches, such as solid-phase permethylation, reductive amination, and reduction.
33829797	6	52	theme	different	1182:1190	arg1	procedures					1201:1210	different standard procedures	1182:1210	different standard procedures across laboratories	1182:1230	Based on different standard procedures across laboratories, this study provides the reference for analysts to select an appropriate N-glycan preparation method with their research purposes.
33829797	0	53	theme	Development	70:80	arg1	Analysis					12:19	Comparative Analysis	0:19	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.	0:145	Comparative Analysis of Different N-glycan Preparation Approaches and Development of Optimized Solid-Phase Permethylation Using Mass Spectrometry.
33829797	4	54	theme	simplified	945:954	arg1	analysis					956:963	simplified analysis	945:963	simplified analysis for N-glycan compositions and high yields using etanercept	945:1022	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
33829797	4	55	theme	solid-phase	844:854	arg1	workflow					878:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	an optimized solid-phase permethylation (OSPP) workflow	831:885	With the comparative analysis, an optimized solid-phase permethylation (OSPP) workflow was developed for mass spectrometric N-glycomics, showing simplified analysis for N-glycan compositions and high yields using etanercept.
34645615	2	0	theme	Care	543:546	arg1	System					548:553	Hoorn Diabetes Care System	528:553	Hoorn Diabetes Care System	528:553	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	2	1	from	DiaGene	506:512	arg1	System					548:553	Hoorn Diabetes Care System	528:553	Hoorn Diabetes Care System	528:553	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	8	2	from	2,6-sialylation	1543:1557	arg1	glycans					1575:1581	triantennary glycans	1562:1581	triantennary glycans	1562:1581	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	2	3	dep	spectrometry	482:493	arg1	n=1815					496:501	n=1815	496:501	n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System	496:553	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	2	4	theme	Hoorn	528:532	arg1	System					548:553	Hoorn Diabetes Care System	528:553	Hoorn Diabetes Care System	528:553	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	2	5	from	n=1518	518:523	arg1	System					548:553	Hoorn Diabetes Care System	528:553	Hoorn Diabetes Care System	528:553	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	10	6	theme	future	1938:1943	arg1	studies					1945:1951	future studies	1938:1951	future studies on prediction biomarkers and potentially disease mechanisms	1938:2011	CONCLUSIONS These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
34645615	8	7	from	increase	1531:1538	arg1	2,6-sialylation					1543:1557	2,6-sialylation	1543:1557	2,6-sialylation on triantennary glycans	1543:1581	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	7	from	increase	1531:1538	arg1	glycans					1575:1581	triantennary glycans	1562:1581	triantennary glycans	1562:1581	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	3	8	dep	technical	610:618	arg1	replicates					620:629	replicates	620:629	replicates	620:629	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	3	9	theme	96-well	650:656	arg1	plates					658:663	96-well plates	650:663	96-well plates	650:663	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	4	10	used	used	728:731	arg2	F					711:711	Peptide:N-glycosidase F	689:711	Peptide:N-glycosidase F (PNGase F)	689:722	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	4	10	used	used	728:731	arg2	F					721:721	PNGase F	714:721	PNGase F	714:721	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	1	11	from	role	255:258	arg1	type					271:274	type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality	271:365	type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality	271:365	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	8	12	from	group	1433:1437	arg1	level					1409:1413	a high level	1402:1413	a high level of bisection on a group of diantennary glycans	1402:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	12	from	group	1433:1437	arg1	association					1349:1359	The strongest association	1335:1359	The strongest association for prevalent cardiovascular disease	1335:1396	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	9	13	theme	Several	1632:1638	arg1	sialylation					1706:1716	sialylation	1706:1716	sialylation	1706:1716	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	13	theme	Several	1632:1638	arg1	galactosylation					1685:1699	galactosylation	1685:1699	galactosylation	1685:1699	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	13	theme	Several	1632:1638	arg1	features					1651:1658	Several other TPNG features	1632:1658	Several other TPNG features	1632:1658	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	13	theme	Several	1632:1638	arg1	fucosylation					1671:1682	fucosylation	1671:1682	fucosylation	1671:1682	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	3	14	theme	randomized	670:679	arg1	manner					681:686	a randomized manner	668:686	a randomized manner	668:686	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	1	15	theme	diabetes-related	326:341	arg1	morbidity					343:351	diabetes-related morbidity	326:351	diabetes-related morbidity	326:351	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	4	16	dep	release	736:742	arg1	derivatized					784:794	derivatized	784:794	were derivatized for stabilization and linkage differentiation	779:840	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	9	17	theme	other	1640:1644	arg1	sialylation					1706:1716	sialylation	1706:1716	sialylation	1706:1716	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	17	theme	other	1640:1644	arg1	galactosylation					1685:1699	galactosylation	1685:1699	galactosylation	1685:1699	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	17	theme	other	1640:1644	arg1	features					1651:1658	Several other TPNG features	1632:1658	Several other TPNG features	1632:1658	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	17	theme	other	1640:1644	arg1	fucosylation					1671:1682	fucosylation	1671:1682	fucosylation	1671:1682	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	10	18	dep	CONCLUSIONS	1814:1824	arg1	provide					1845:1851	provide	1845:1851	provide	1845:1851	CONCLUSIONS These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
34645615	5	19	theme	glycosylation	1016:1028	arg1	features					1004:1011	structural features	993:1011	structural features of glycosylation	993:1028	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	4	20	theme	linkage	818:824	arg1	differentiation					826:840	linkage differentiation	818:840	linkage differentiation	818:840	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	8	21	theme	glycans	1454:1460	arg1	glycans					1454:1460	diantennary glycans	1442:1460	diantennary glycans	1442:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	21	theme	glycans	1454:1460	arg1	group					1433:1437	a group	1431:1437	a group of diantennary glycans	1431:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	6	22	theme	independent	1187:1197	arg1	cohorts					1199:1205	both independent cohorts	1182:1205	both independent cohorts	1182:1205	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	5	23	theme	total	849:853	arg1	normalization					860:872	total area normalization	849:872	total area normalization	849:872	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	3	24	theme	RESEARCH	557:564	arg1	DESIGN					566:571	RESEARCH DESIGN	557:571	RESEARCH DESIGN	557:571	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	0	25	from	retinopathy	91:101	arg1	diabetes					113:120	type 2 diabetes	106:120	type 2 diabetes	106:120	Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
34645615	6	26	theme	Cox	1164:1166	arg1	regression					1168:1177	Cox regression	1164:1177	Cox regression	1164:1177	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	8	27	dep	A2FS0B	1463:1468	arg1	p=1.34×10-11					1480:1491	p=1.34×10-11	1480:1491	p=1.34×10-11	1480:1491	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	27	dep	A2FS0B	1463:1468	arg1	OR=1.38					1471:1477	OR=1.38	1471:1477	OR=1.38	1471:1477	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	28	dep	level	1409:1413	arg1	A2FS0B					1463:1468	A2FS0B	1463:1468	A2FS0B	1463:1468	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	9	29	theme	prevalent	1757:1765	arg1	complications					1780:1792	prevalent and incident complications	1757:1792	prevalent and incident complications of type 2 diabetes	1757:1811	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	10	30	from	studies	1945:1951	arg1	biomarkers					1967:1976	prediction biomarkers	1956:1976	prediction biomarkers	1956:1976	CONCLUSIONS These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
34645615	10	30	from	studies	1945:1951	arg1	mechanisms					2002:2011	disease mechanisms	1994:2011	disease mechanisms	1994:2011	CONCLUSIONS These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
34645615	1	31	theme	plasma	167:172	arg1	TPNG					185:188	TPNG	185:188	TPNG	185:188	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	31	theme	plasma	167:172	arg1	N-glycome					174:182	total plasma N-glycome	161:182	total plasma N-glycome (TPNG)	161:189	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	9	32	theme	incident	1771:1778	arg1	complications					1780:1792	prevalent and incident complications	1757:1792	prevalent and incident complications of type 2 diabetes	1757:1811	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	4	33	theme	N-glycosidase	697:709	arg1	F					711:711	Peptide:N-glycosidase F	689:711	Peptide:N-glycosidase F (PNGase F)	689:722	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	4	33	theme	N-glycosidase	697:709	arg1	F					721:721	PNGase F	714:721	PNGase F	714:721	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	2	34	theme	Dutch	457:461	arg1	cohorts					463:469	two Dutch cohorts	453:469	two Dutch cohorts	453:469	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	0	35	theme	type	106:109	arg1	diabetes					113:120	type 2 diabetes	106:120	type 2 diabetes	106:120	Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
34645615	1	36	theme	type	319:322	arg1	complications					287:299	diabetes complications	278:299	diabetes complications	278:299	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	36	theme	type	319:322	arg1	cause					310:314	a major cause	302:314	a major cause of type 2 diabetes-related morbidity and mortality	302:365	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	37	dep	type	271:274	arg1	complications					287:299	diabetes complications	278:299	diabetes complications	278:299	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	37	dep	type	271:274	arg1	cause					310:314	a major cause	302:314	a major cause of type 2 diabetes-related morbidity and mortality	302:365	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	8	38	theme	cardiovascular	1375:1388	arg1	disease					1390:1396	prevalent cardiovascular disease	1365:1396	prevalent cardiovascular disease	1365:1396	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	0	39	theme	Plasma	0:5	arg1	N-glycosylation					15:29	Plasma protein N-glycosylation	0:29	Plasma protein N-glycosylation	0:29	Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
34645615	7	40	theme	prevalent	1310:1318	arg1	complications					1320:1332	incident and prevalent complications	1297:1332	incident and prevalent complications	1297:1332	RESULTS Our results demonstrated similarities between incident and prevalent complications.
34645615	2	41	theme	TPNG	386:389	arg1	complications					422:434	TPNG in relation to type 2 diabetes complications	386:434	TPNG in relation to type 2 diabetes complications	386:434	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	4	42	theme	Peptide	689:695	arg1	F					711:711	Peptide:N-glycosidase F	689:711	Peptide:N-glycosidase F (PNGase F)	689:722	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	4	42	theme	Peptide	689:695	arg1	F					721:721	PNGase F	714:721	PNGase F	714:721	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	5	43	theme	glycan	889:894	arg1	compositions					896:907	68 individual glycan compositions	875:907	68 individual glycan compositions	875:907	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	7	44	theme	incident	1297:1304	arg1	complications					1320:1332	incident and prevalent complications	1297:1332	incident and prevalent complications	1297:1332	RESULTS Our results demonstrated similarities between incident and prevalent complications.
34645615	3	45	theme	Blood	585:589	arg1	samples					598:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	8	46	theme	high	1404:1407	arg1	level					1409:1413	a high level	1402:1413	a high level of bisection on a group of diantennary glycans	1402:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	46	theme	high	1404:1407	arg1	association					1349:1359	The strongest association	1335:1359	The strongest association for prevalent cardiovascular disease	1335:1396	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	2	47	theme	type	406:409	arg1	diabetes					413:420	type 2 diabetes	406:420	type 2 diabetes	406:420	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	8	48	theme	triantennary	1562:1573	arg1	glycans					1575:1581	triantennary glycans	1562:1581	triantennary glycans	1562:1581	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	5	49	used	used	943:946	arg2	compositions					896:907	68 individual glycan compositions	875:907	68 individual glycan compositions	875:907	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	0	50	theme	cardiovascular	50:63	arg1	disease					65:71	cardiovascular disease	50:71	cardiovascular disease	50:71	Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
34645615	5	51	theme	derived	964:970	arg1	traits					972:977	45 derived traits	961:977	45 derived traits which reflect structural features of glycosylation	961:1028	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	10	52	theme	TPNG	1869:1872	arg1	patterns					1874:1881	TPNG patterns	1869:1881	TPNG patterns	1869:1881	CONCLUSIONS These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
34645615	6	53	theme	glycan	1047:1052	arg1	features					1054:1061	glycan features	1047:1061	glycan features with prevalent and incident microvascular or macrovascular complications	1047:1134	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	2	54	theme	Diabetes	534:541	arg1	System					548:553	Hoorn Diabetes Care System	528:553	Hoorn Diabetes Care System	528:553	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	9	55	theme	TPNG	1646:1649	arg1	sialylation					1706:1716	sialylation	1706:1716	sialylation	1706:1716	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	55	theme	TPNG	1646:1649	arg1	galactosylation					1685:1699	galactosylation	1685:1699	galactosylation	1685:1699	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	55	theme	TPNG	1646:1649	arg1	features					1651:1658	Several other TPNG features	1632:1658	Several other TPNG features	1632:1658	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	9	55	theme	TPNG	1646:1649	arg1	fucosylation					1671:1682	fucosylation	1671:1682	fucosylation	1671:1682	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	8	56	from	level	1409:1413	arg1	glycans					1454:1460	diantennary glycans	1442:1460	diantennary glycans	1442:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	56	from	level	1409:1413	arg1	group					1433:1437	a group	1431:1437	a group of diantennary glycans	1431:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	1	57	theme	N-glycome	174:182	arg1	associations					145:156	associations	145:156	associations of total plasma N-glycome (TPNG) with type 2 diabetes	145:210	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	6	58	with	features	1054:1061	arg1	complications					1122:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	8	59	theme	bisection	1418:1426	arg1	level					1409:1413	a high level	1402:1413	a high level of bisection on a group of diantennary glycans	1402:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	59	theme	bisection	1418:1426	arg1	association					1349:1359	The strongest association	1335:1359	The strongest association for prevalent cardiovascular disease	1335:1396	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	60	from	glycans	1575:1581	arg1	A3E					1604:1606	A3E	1604:1606	A3E	1604:1606	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	60	from	glycans	1575:1581	arg1	increase					1531:1538	the increase	1527:1538	the increase in 2,6-sialylation on triantennary glycans	1527:1581	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	60	from	glycans	1575:1581	arg1	pronounced					1592:1601	pronounced	1592:1601	pronounced	1592:1601	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	4	61	theme	sialic	766:771	arg1	acids					773:777	sialic acids	766:777	sialic acids	766:777	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	6	62	theme	macrovascular	1108:1120	arg1	complications					1122:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	10	63	theme	prediction	1956:1965	arg1	biomarkers					1967:1976	prediction biomarkers	1956:1976	prediction biomarkers	1956:1976	CONCLUSIONS These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
34645615	8	64	theme	diantennary	1442:1452	arg1	glycans					1454:1460	diantennary glycans	1442:1460	diantennary glycans	1442:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	6	65	theme	microvascular	1091:1103	arg1	complications					1122:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	8	66	from	bisection	1418:1426	arg1	glycans					1454:1460	diantennary glycans	1442:1460	diantennary glycans	1442:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	66	from	bisection	1418:1426	arg1	group					1433:1437	a group	1431:1437	a group of diantennary glycans	1431:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	5	67	link	derived	964:970	arg1	traits					972:977	45 derived traits	961:977	45 derived traits which reflect structural features of glycosylation	961:1028	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	2	68	theme	mass	477:480	arg1	spectrometry					482:493	mass spectrometry	477:493	mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System)	477:554	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	0	69	from	nephropathy	74:84	arg1	diabetes					113:120	type 2 diabetes	106:120	type 2 diabetes	106:120	Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
34645615	10	70	theme	disease	1994:2000	arg1	mechanisms					2002:2011	disease mechanisms	1994:2011	disease mechanisms	1994:2011	CONCLUSIONS These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.
34645615	5	71	theme	area	855:858	arg1	normalization					860:872	total area normalization	849:872	total area normalization	849:872	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	8	72	theme	strongest	1339:1347	arg1	association					1349:1359	The strongest association	1335:1359	The strongest association for prevalent cardiovascular disease	1335:1396	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	72	theme	strongest	1339:1347	arg1	level					1409:1413	a high level	1402:1413	a high level of bisection on a group of diantennary glycans	1402:1460	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	5	73	theme	structural	993:1002	arg1	features					1004:1011	structural features	993:1011	structural features of glycosylation	993:1028	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	9	74	with	associations	1739:1750	arg1	complications					1780:1792	prevalent and incident complications	1757:1792	prevalent and incident complications of type 2 diabetes	1757:1811	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	2	75	from	TPNG	386:389	arg1	relation					394:401	relation	394:401	relation to type 2 diabetes	394:420	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	1	76	theme	total	161:165	arg1	TPNG					185:188	TPNG	185:188	TPNG	185:188	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	76	theme	total	161:165	arg1	N-glycome					174:182	total plasma N-glycome	161:182	total plasma N-glycome (TPNG)	161:189	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	0	77	from	disease	65:71	arg1	diabetes					113:120	type 2 diabetes	106:120	type 2 diabetes	106:120	Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
34645615	2	78	from	relation	394:401	arg1	TPNG					386:389	TPNG	386:389	TPNG	386:389	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	1	79	theme	major	304:308	arg1	complications					287:299	diabetes complications	278:299	diabetes complications	278:299	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	79	theme	major	304:308	arg1	cause					310:314	a major cause	302:314	a major cause of type 2 diabetes-related morbidity and mortality	302:365	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	80	with	associations	145:156	arg1	diabetes					203:210	type 2 diabetes	196:210	type 2 diabetes	196:210	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	2	81	theme	cohorts	463:469	arg1	subsamples					439:448	subsamples	439:448	subsamples of two Dutch cohorts	439:469	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	8	82	theme	prevalent	1505:1513	arg1	nephropathy					1515:1525	prevalent nephropathy	1505:1525	prevalent nephropathy	1505:1525	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	83	dep	A3E	1604:1606	arg1	p=9.70×10-6					1618:1628	p=9.70×10-6	1618:1628	p=9.70×10-6	1618:1628	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	83	dep	A3E	1604:1606	arg1	OR=1.28					1609:1615	OR=1.28	1609:1615	OR=1.28	1609:1615	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	1	84	theme	type	196:199	arg1	diabetes					203:210	type 2 diabetes	196:210	type 2 diabetes	196:210	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	8	85	gly	2,6-sialylation	1543:1557	arg1	glycans					1575:1581	triantennary glycans	1562:1581	triantennary glycans	1562:1581	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	9	86	theme	type	1797:1800	arg1	diabetes					1804:1811	type 2 diabetes	1797:1811	type 2 diabetes	1797:1811	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	0	87	theme	protein	7:13	arg1	N-glycosylation					15:29	Plasma protein N-glycosylation	0:29	Plasma protein N-glycosylation	0:29	Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes.
34645615	8	88	dep	pronounced	1592:1601	arg1	A3E					1604:1606	A3E	1604:1606	A3E	1604:1606	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	88	dep	pronounced	1592:1601	arg1	increase					1531:1538	the increase	1527:1538	the increase in 2,6-sialylation on triantennary glycans	1527:1581	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	8	88	dep	pronounced	1592:1601	arg1	pronounced					1592:1601	pronounced	1592:1601	pronounced	1592:1601	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	9	89	theme	diabetes	1804:1811	arg1	complications					1780:1792	prevalent and incident complications	1757:1792	prevalent and incident complications of type 2 diabetes	1757:1811	Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.
34645615	8	90	theme	prevalent	1365:1373	arg1	disease					1390:1396	prevalent cardiovascular disease	1365:1396	prevalent cardiovascular disease	1365:1396	The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34×10-11), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70×10-6).
34645615	5	91	theme	individual	878:887	arg1	compositions					896:907	68 individual glycan compositions	875:907	68 individual glycan compositions	875:907	After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation.
34645615	3	92	theme	METHODS	577:583	arg1	samples					598:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	1	93	theme	TPNG	263:266	arg1	role					255:258	the role	251:258	the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality	251:365	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	94	dep	type	319:322	arg1	mortality					357:365	mortality	357:365	mortality	357:365	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	94	dep	type	319:322	arg1	morbidity					343:351	diabetes-related morbidity	326:351	diabetes-related morbidity	326:351	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	3	95	theme	DESIGN	566:571	arg1	samples					598:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	6	96	theme	incident	1082:1089	arg1	complications					1122:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	1	97	theme	diabetes	278:285	arg1	complications					287:299	diabetes complications	278:299	diabetes complications	278:299	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	1	97	theme	diabetes	278:285	arg1	cause					310:314	a major cause	302:314	a major cause of type 2 diabetes-related morbidity and mortality	302:365	INTRODUCTION Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality.
34645615	7	98	dep	demonstrated	1263:1274	arg1	RESULTS					1243:1249	RESULTS	1243:1249	RESULTS	1243:1249	RESULTS Our results demonstrated similarities between incident and prevalent complications.
34645615	6	99	theme	prevalent	1068:1076	arg1	complications					1122:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	prevalent and incident microvascular or macrovascular complications	1068:1134	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	3	100	theme	plasma	591:596	arg1	samples					598:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples	557:604	RESEARCH DESIGN AND METHODS Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner.
34645615	4	101	theme	PNGase	714:719	arg1	F					711:711	Peptide:N-glycosidase F	689:711	Peptide:N-glycosidase F (PNGase F)	689:722	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	4	101	theme	PNGase	714:719	arg1	F					721:721	PNGase F	714:721	PNGase F	714:721	Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation.
34645615	6	102	theme	features	1054:1061	arg1	Associations					1031:1042	Associations	1031:1042	Associations of glycan features with prevalent and incident microvascular or macrovascular complications	1031:1134	Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.
34645615	2	103	from	n=1815	496:501	arg1	DiaGene					506:512	DiaGene	506:512	DiaGene	506:512	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
34645615	2	103	from	n=1815	496:501	arg1	n=1518					518:523	n=1518	518:523	n=1518	518:523	Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).
32764711	2	0	theme	virus	335:339	arg1	egress					341:346	virus egress	335:346	virus egress in mammalian cells, but not in tick cells	335:388	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	1	1	theme	tick	254:257	arg1	bite					259:262	a tick bite	252:262	a tick bite	252:262	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	9	2	theme	protein	1629:1635	arg1	structure					1637:1645	the E protein structure	1623:1645	the E protein structure	1623:1645	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	6	3	with	structure	905:913	arg1	Gal2GlcNAc2Man3GlcNAc2Fuc					933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	3	with	structure	905:913	arg1	fucose					925:930	core fucose	920:930	core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	920:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	3	with	structure	905:913	arg1	Man5GlcNAc2					854:864	Man5GlcNAc2	854:864	Man5GlcNAc2	854:864	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	3	with	structure	905:913	arg1	residues					844:851	five mannose residues	831:851	five mannose residues (Man5GlcNAc2)	831:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	4	4	theme	study	549:553	arg1	purpose					534:540	the main purpose	525:540	the main purpose of our study	525:553	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	6	5	theme	human	1143:1147	arg1	cells					1158:1162	human neuronal cells	1143:1162	human neuronal cells	1143:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	0	6	theme	Comprehensive	0:12	arg1	mapping					30:36	Comprehensive N-glycosylation mapping	0:36	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.	0:127	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	1	7	theme	causative	173:181	arg1	agent					183:187	the causative agent	169:187	the causative agent of severe human neuroinfections that most commonly occur after a tick bite	169:262	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	1	7	theme	causative	173:181	arg1	virus					153:157	Tick-borne encephalitis virus	129:157	Tick-borne encephalitis virus (TBEV)	129:164	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	2	8	theme	E	303:303	arg1	glycoprotein					306:317	the TBEV envelope (E) glycoprotein	284:317	the TBEV envelope (E) glycoprotein	284:317	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	8	9	with	structures	1435:1444	arg1	Man5-6GlcNAc2					1474:1486	Man5-6GlcNAc2	1474:1486	Man5-6GlcNAc2	1474:1486	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	8	9	with	structures	1435:1444	arg1	mannoses					1464:1471	five and six mannoses	1451:1471	five and six mannoses (Man5-6GlcNAc2)	1451:1487	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	5	10	theme	significant	763:773	arg1	differences					775:785	significant differences	763:785	significant differences in these profiles	763:803	Mass spectrometric analysis revealed significant differences in these profiles.
32764711	6	11	theme	galactosylated	890:903	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	11	theme	galactosylated	890:903	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	11	theme	galactosylated	890:903	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	11	theme	galactosylated	890:903	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	11	theme	galactosylated	890:903	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	9	12	theme	carbohydrate-binding	1687:1706	arg1	agents					1718:1723	carbohydrate-binding antiviral agents	1687:1723	carbohydrate-binding antiviral agents active against TBEV	1687:1743	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	5	13	from	differences	775:785	arg1	profiles					796:803	these profiles	790:803	these profiles	790:803	Mass spectrometric analysis revealed significant differences in these profiles.
32764711	6	14	theme	complex	870:876	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	14	theme	complex	870:876	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	14	theme	complex	870:876	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	14	theme	complex	870:876	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	14	theme	complex	870:876	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	15	with	group	967:971	arg1	Gal2GlcNAc2Man3GlcNAc2Fuc					933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	15	with	group	967:971	arg1	fucose					925:930	core fucose	920:930	core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	920:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	15	with	group	967:971	arg1	Man5GlcNAc2					854:864	Man5GlcNAc2	854:864	Man5GlcNAc2	854:864	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	15	with	group	967:971	arg1	residues					844:851	five mannose residues	831:851	five mannose residues (Man5GlcNAc2)	831:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	4	16	theme	human	645:649	arg1	cells					660:664	human neuronal cells	645:664	human neuronal cells	645:664	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	8	17	with	paucimannose	1382:1393	arg1	Man5-6GlcNAc2					1474:1486	Man5-6GlcNAc2	1474:1486	Man5-6GlcNAc2	1474:1486	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	8	17	with	paucimannose	1382:1393	arg1	mannoses					1464:1471	five and six mannoses	1451:1471	five and six mannoses (Man5-6GlcNAc2)	1451:1487	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	1	18	theme	Tick-borne	129:138	arg1	agent					183:187	the causative agent	169:187	the causative agent of severe human neuroinfections that most commonly occur after a tick bite	169:262	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	1	18	theme	Tick-borne	129:138	arg1	TBEV					160:163	TBEV	160:163	TBEV	160:163	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	1	18	theme	Tick-borne	129:138	arg1	virus					153:157	Tick-borne encephalitis virus	129:157	Tick-borne encephalitis virus (TBEV)	129:164	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	4	19	theme	TBEV	626:629	arg1	protein					615:621	the E protein	609:621	the E protein of TBEV	609:629	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	0	20	theme	encephalitis	79:90	arg1	virus					92:96	tick-borne encephalitis virus	68:96	tick-borne encephalitis virus grown in human and tick cells	68:126	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	0	21	theme	human	107:111	arg1	cells					122:126	human and tick cells	107:126	human and tick cells	107:126	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	9	22	from	data	1615:1618	arg1	structure					1637:1645	the E protein structure	1623:1645	the E protein structure	1623:1645	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	4	23	theme	virus	699:703	arg1	profile					688:694	the profile	684:694	the profile of virus grown in tick cells	684:723	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	0	24	theme	tick	117:120	arg1	cells					122:126	human and tick cells	107:126	human and tick cells	107:126	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	0	25	theme	glycoprotein	50:61	arg1	mapping					30:36	Comprehensive N-glycosylation mapping	0:36	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.	0:127	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	2	26	theme	glycoprotein	306:317	arg1	N-Glycosylation					265:279	N-Glycosylation	265:279	N-Glycosylation of the TBEV envelope (E) glycoprotein	265:317	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	8	27	theme	major	1494:1498	arg1	glycans					1500:1506	major glycans	1494:1506	major glycans on the viral surface	1494:1527	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	5	28	theme	Mass	726:729	arg1	analysis					745:752	Mass spectrometric analysis	726:752	Mass spectrometric analysis	726:752	Mass spectrometric analysis revealed significant differences in these profiles.
32764711	9	29	from	crystallography	1571:1585	arg1	structure					1637:1645	the E protein structure	1623:1645	the E protein structure	1623:1645	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	7	30	theme	E	1306:1306	arg1	protein					1308:1314	the E protein	1302:1314	the E protein	1302:1314	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	7	31	gly	glycopeptides	1222:1234	arg2	glycopeptides					1222:1234	the glycopeptides	1218:1234	the glycopeptides	1218:1234	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	6	32	theme	High-mannose	806:817	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	32	theme	High-mannose	806:817	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	32	theme	High-mannose	806:817	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	32	theme	High-mannose	806:817	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	32	theme	High-mannose	806:817	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	33	theme	glycans	983:989	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	33	theme	glycans	983:989	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	33	theme	glycans	983:989	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	33	theme	glycans	983:989	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	33	theme	glycans	983:989	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	8	34	theme	viral	1515:1519	arg1	surface					1521:1527	the viral surface	1511:1527	the viral surface	1511:1527	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	6	35	link	asparagine-linked	1072:1088	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	35	link	asparagine-linked	1072:1088	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	35	link	asparagine-linked	1072:1088	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	35	link	asparagine-linked	1072:1088	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	35	link	asparagine-linked	1072:1088	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	8	36	theme	tick	1359:1362	arg1	cells					1364:1368	tick cells	1359:1368	tick cells	1359:1368	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	2	37	theme	tick	379:382	arg1	cells					384:388	tick cells	379:388	tick cells	379:388	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	0	38	theme	envelope	41:48	arg1	glycoprotein					50:61	envelope glycoprotein	41:61	envelope glycoprotein	41:61	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	9	39	theme	existing	1562:1569	arg1	crystallography					1571:1585	existing crystallography and cryoelectron tomography data	1562:1618	crystallography	1571:1585	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	7	40	theme	glycosylation	1280:1292	arg1	site					1294:1297	the glycosylation site	1276:1297	the glycosylation site in the E protein	1276:1314	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	3	41	theme	antigenic	448:456	arg1	sites					458:462	specific antigenic sites	439:462	specific antigenic sites	439:462	In addition, glycans have been reported to mask specific antigenic sites from recognition by neutralizing antibodies.
32764711	7	42	from	site	1294:1297	arg1	protein					1308:1314	the E protein	1302:1314	the E protein	1302:1314	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	2	43	gly	glycoprotein	306:317	arg1	glycoprotein					306:317	the TBEV envelope (E) glycoprotein	284:317	the TBEV envelope (E) glycoprotein	284:317	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	9	44	theme	tomography	1604:1613	arg1	data					1615:1618	existing crystallography and cryoelectron tomography data	1562:1618	data	1615:1618	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	7	45	theme	additional	1247:1256	arg1	information					1258:1268	additional information	1247:1268	additional information about the glycosylation site in the E protein	1247:1314	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	4	46	attach	linked	599:604	arg1	protein					615:621	the E protein	609:621	the E protein of TBEV	609:629	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	4	46	attach	linked	599:604	arg2	N-glycans					589:597	N-glycans	589:597	N-glycans linked to the E protein of TBEV when grown in human neuronal cells	589:664	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	2	47	theme	mammalian	351:359	arg1	cells					361:365	mammalian cells	351:365	mammalian cells	351:365	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	6	48	with	glycan	819:824	arg1	Gal2GlcNAc2Man3GlcNAc2Fuc					933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	48	with	glycan	819:824	arg1	fucose					925:930	core fucose	920:930	core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	920:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	48	with	glycan	819:824	arg1	Man5GlcNAc2					854:864	Man5GlcNAc2	854:864	Man5GlcNAc2	854:864	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	48	with	glycan	819:824	arg1	residues					844:851	five mannose residues	831:851	five mannose residues (Man5GlcNAc2)	831:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	9	49	theme	E	1627:1627	arg1	structure					1637:1645	the E protein structure	1623:1645	the E protein structure	1623:1645	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	2	50	theme	TBEV	288:291	arg1	glycoprotein					306:317	the TBEV envelope (E) glycoprotein	284:317	the TBEV envelope (E) glycoprotein	284:317	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	6	51	theme	mannose	836:842	arg1	Man5GlcNAc2					854:864	Man5GlcNAc2	854:864	Man5GlcNAc2	854:864	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	51	theme	mannose	836:842	arg1	residues					844:851	five mannose residues	831:851	five mannose residues (Man5GlcNAc2)	831:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	52	theme	neuronal	1149:1156	arg1	cells					1158:1162	human neuronal cells	1143:1162	human neuronal cells	1143:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	2	53	gly	N-Glycosylation	265:279	arg1	glycoprotein					306:317	the TBEV envelope (E) glycoprotein	284:317	the TBEV envelope (E) glycoprotein	284:317	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	2	54	from	egress	341:346	arg1	cells					361:365	mammalian cells	351:365	mammalian cells	351:365	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	2	54	from	egress	341:346	arg1	cells					384:388	tick cells	379:388	tick cells	379:388	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	6	55	theme	core	920:923	arg1	Gal2GlcNAc2Man3GlcNAc2Fuc					933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	Gal2GlcNAc2Man3GlcNAc2Fuc	933:957	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	55	theme	core	920:923	arg1	fucose					925:930	core fucose	920:930	core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	920:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	56	theme	TBEV	1125:1128	arg1	surface					1114:1120	the surface	1110:1120	the surface of TBEV derived from human neuronal cells	1110:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	4	57	theme	E	613:613	arg1	protein					615:621	the E protein	609:621	the E protein of TBEV	609:629	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	1	58	theme	severe	192:197	arg1	neuroinfections					205:219	severe human neuroinfections	192:219	severe human neuroinfections that most commonly occur after a tick bite	192:262	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	1	59	theme	neuroinfections	205:219	arg1	agent					183:187	the causative agent	169:187	the causative agent of severe human neuroinfections that most commonly occur after a tick bite	169:262	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	1	59	theme	neuroinfections	205:219	arg1	virus					153:157	Tick-borne encephalitis virus	129:157	Tick-borne encephalitis virus (TBEV)	129:164	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	6	60	theme	biantennary	878:888	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	60	theme	biantennary	878:888	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	60	theme	biantennary	878:888	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	60	theme	biantennary	878:888	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	60	theme	biantennary	878:888	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	9	61	theme	antiviral	1708:1716	arg1	agents					1718:1723	carbohydrate-binding antiviral agents	1687:1723	carbohydrate-binding antiviral agents active against TBEV	1687:1743	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	0	62	from	virus	92:96	arg1	mapping					30:36	Comprehensive N-glycosylation mapping	0:36	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.	0:127	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	4	63	theme	N-glycans	589:597	arg1	profile					578:584	the profile	574:584	the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells	574:664	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	9	64	theme	active	1725:1730	arg1	agents					1718:1723	carbohydrate-binding antiviral agents	1687:1723	carbohydrate-binding antiviral agents active against TBEV	1687:1743	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	1	65	theme	encephalitis	140:151	arg1	agent					183:187	the causative agent	169:187	the causative agent of severe human neuroinfections that most commonly occur after a tick bite	169:262	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	1	65	theme	encephalitis	140:151	arg1	TBEV					160:163	TBEV	160:163	TBEV	160:163	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	1	65	theme	encephalitis	140:151	arg1	virus					153:157	Tick-borne encephalitis virus	129:157	Tick-borne encephalitis virus (TBEV)	129:164	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	4	66	theme	neuronal	651:658	arg1	cells					660:664	human neuronal cells	645:664	human neuronal cells	645:664	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	6	67	attach	derived	1130:1136	arg1	cells					1158:1162	human neuronal cells	1143:1162	human neuronal cells	1143:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	67	attach	derived	1130:1136	arg2	TBEV					1125:1128	TBEV	1125:1128	TBEV derived from human neuronal cells	1125:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	7	68	theme	observed	1169:1176	arg1	pattern					1178:1184	The observed pattern	1165:1184	The observed pattern	1165:1184	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	0	69	gly	glycoprotein	50:61	arg1	glycoprotein					50:61	envelope glycoprotein	41:61	envelope glycoprotein	41:61	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	7	70	gly	glycosylation	1280:1292	arg2	site					1294:1297	the glycosylation site	1276:1297	the glycosylation site in the E protein	1276:1314	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	2	71	theme	envelope	293:300	arg1	glycoprotein					306:317	the TBEV envelope (E) glycoprotein	284:317	the TBEV envelope (E) glycoprotein	284:317	N-Glycosylation of the TBEV envelope (E) glycoprotein is critical for virus egress in mammalian cells, but not in tick cells.
32764711	6	72	theme	asparagine-linked	1072:1088	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	72	theme	asparagine-linked	1072:1088	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	72	theme	asparagine-linked	1072:1088	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	72	theme	asparagine-linked	1072:1088	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	72	theme	asparagine-linked	1072:1088	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	1	73	theme	human	199:203	arg1	neuroinfections					205:219	severe human neuroinfections	192:219	severe human neuroinfections that most commonly occur after a tick bite	192:262	Tick-borne encephalitis virus (TBEV) is the causative agent of severe human neuroinfections that most commonly occur after a tick bite.
32764711	0	74	theme	N-glycosylation	14:28	arg1	mapping					30:36	Comprehensive N-glycosylation mapping	0:36	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.	0:127	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	6	75	theme	composition	1000:1010	arg1	Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1					1012:1043	the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	996:1043	the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	996:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	5	76	theme	spectrometric	731:743	arg1	analysis					745:752	Mass spectrometric analysis	726:752	Mass spectrometric analysis	726:752	Mass spectrometric analysis revealed significant differences in these profiles.
32764711	9	77	theme	reported	1534:1541	arg1	instrumental					1660:1671	instrumental	1660:1671	instrumental	1660:1671	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	9	77	theme	reported	1534:1541	arg1	results					1543:1549	The reported results	1530:1549	The reported results	1530:1549	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	4	78	theme	main	529:532	arg1	purpose					534:540	the main purpose	525:540	the main purpose of our study	525:553	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	8	79	theme	TBEV	1345:1348	arg1	profile					1334:1340	the profile	1330:1340	the profile of TBEV grown in tick cells	1330:1368	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	6	80	theme	main	1067:1070	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	80	theme	main	1067:1070	arg1	oligosaccharides					1090:1105	the main asparagine-linked oligosaccharides	1063:1105	the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells	1063:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	80	theme	main	1067:1070	arg1	glycan					819:824	High-mannose glycan	806:824	High-mannose glycan with five mannose residues (Man5GlcNAc2)	806:865	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	80	theme	main	1067:1070	arg1	structure					905:913	a complex biantennary galactosylated structure	868:913	a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc)	868:958	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	80	theme	main	1067:1070	arg1	group					967:971	a group	965:971	a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	965:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	8	81	from	glycans	1500:1506	arg1	surface					1521:1527	the viral surface	1511:1527	the viral surface	1511:1527	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	6	82	theme	hybrid	976:981	arg1	glycans					983:989	hybrid glycans	976:989	hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	976:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	6	83	from	oligosaccharides	1090:1105	arg1	surface					1114:1120	the surface	1110:1120	the surface of TBEV derived from human neuronal cells	1110:1162	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	0	84	theme	tick-borne	68:77	arg1	virus					92:96	tick-borne encephalitis virus	68:96	tick-borne encephalitis virus grown in human and tick cells	68:126	Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
32764711	8	85	theme	high-mannose	1422:1433	arg1	structures					1435:1444	high-mannose structures	1422:1444	high-mannose structures with five and six mannoses (Man5-6GlcNAc2)	1422:1487	In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
32764711	9	86	theme	cryoelectron	1591:1602	arg1	data					1615:1618	existing crystallography and cryoelectron tomography data	1562:1618	data	1615:1618	The reported results complement existing crystallography and cryoelectron tomography data on the E protein structure and could be instrumental for designing carbohydrate-binding antiviral agents active against TBEV.
32764711	3	87	theme	specific	439:446	arg1	sites					458:462	specific antigenic sites	439:462	specific antigenic sites	439:462	In addition, glycans have been reported to mask specific antigenic sites from recognition by neutralizing antibodies.
32764711	6	88	with	glycans	983:989	arg1	Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1					1012:1043	the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	996:1043	the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1	996:1043	High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells.
32764711	7	89	theme	glycopeptides	1222:1234	arg1	examination					1203:1213	examination	1203:1213	examination of the glycopeptides	1203:1234	The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein.
32764711	4	90	theme	tick	714:717	arg1	cells					719:723	tick cells	714:723	tick cells	714:723	In this regard, the main purpose of our study was to investigate the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells and compare it to the profile of virus grown in tick cells.
32764711	3	91	theme	neutralizing	484:495	arg1	antibodies					497:506	neutralizing antibodies	484:506	neutralizing antibodies	484:506	In addition, glycans have been reported to mask specific antigenic sites from recognition by neutralizing antibodies.
34687007	8	0	theme	lectin	1429:1434	arg1	microarrays					1436:1446	lectin microarrays	1429:1446	lectin microarrays	1429:1446	On the other hand, lectin microarrays have found their application in the rapid screening of glycan profiles on intact proteins.
34687007	5	1	theme	immunoglobulin	917:930	arg1	IgG					935:937	IgG	935:937	IgG	935:937	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	5	1	theme	immunoglobulin	917:930	arg1	G					932:932	immunoglobulin G	917:932	immunoglobulin G (IgG) applications	917:951	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	4	2	theme	lectin-based	593:604	arg1	methods					606:612	lectin-based methods	593:612	lectin-based methods	593:612	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	0	3	theme	Glycosylation	70:82	arg1	Analysis					84:91	Immunoglobulin (G) Glycosylation Analysis	51:91	Immunoglobulin (G) Glycosylation Analysis	51:91	Lectin and Liquid Chromatography-Based Methods for Immunoglobulin (G) Glycosylation Analysis.
34687007	8	4	theme	profiles	1510:1517	arg1	screening					1490:1498	the rapid screening	1480:1498	the rapid screening of glycan profiles on intact proteins	1480:1536	On the other hand, lectin microarrays have found their application in the rapid screening of glycan profiles on intact proteins.
34687007	5	5	dep	N-	859:860	arg1	analysis					882:889	analysis	882:889	analysis	882:889	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	4	6	theme	mass	711:714	arg1	spectrometry					716:727	mass spectrometry	711:727	mass spectrometry	711:727	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	6	7	theme	used	1014:1017	arg1	methods					1022:1028	the most often used LC methods	999:1028	the most often used LC methods for Ig purification	999:1048	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	8	8	theme	glycan	1503:1508	arg1	profiles					1510:1517	glycan profiles	1503:1517	glycan profiles	1503:1517	On the other hand, lectin microarrays have found their application in the rapid screening of glycan profiles on intact proteins.
34687007	2	9	theme	biomarker	295:303	arg1	potential					305:313	a promising biomarker potential	283:313	a promising biomarker potential for diagnosis and prognosis of disease advancement	283:364	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	6	10	theme	free	1142:1145	arg1	glycans					1147:1153	free glycans	1142:1153	free glycans	1142:1153	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	3	11	theme	other	374:378	arg1	hand					380:383	the other hand	370:383	the other hand	370:383	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	8	12	theme	intact	1522:1527	arg1	proteins					1529:1536	intact proteins	1522:1536	intact proteins	1522:1536	On the other hand, lectin microarrays have found their application in the rapid screening of glycan profiles on intact proteins.
34687007	7	13	gly	glycoprotein	1300:1311	arg1	glycoprotein					1300:1311	glycoprotein purification	1300:1324	glycoprotein purification	1300:1324	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	5	14	from	focus	908:912	arg1	applications					940:951	immunoglobulin G (IgG) applications	917:951	immunoglobulin G (IgG) applications	917:951	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	2	15	theme	promising	285:293	arg1	potential					305:313	a promising biomarker potential	283:313	a promising biomarker potential for diagnosis and prognosis of disease advancement	283:364	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	7	16	theme	lectin-carbohydrate	1263:1281	arg1	interactions					1283:1294	lectin-carbohydrate interactions	1263:1294	lectin-carbohydrate interactions	1263:1294	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	2	17	theme	advancement	354:364	arg1	prognosis					333:341	prognosis	333:341	prognosis	333:341	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	2	17	theme	advancement	354:364	arg1	diagnosis					319:327	diagnosis	319:327	diagnosis	319:327	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	5	18	gly	O-glycosylation	866:880	arg1	Igs					894:896	Igs	894:896	Igs	894:896	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	7	19	dep	Igs	1372:1374	arg1	purification					1376:1387	purification	1376:1387	purification	1376:1387	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	19	dep	Igs	1372:1374	arg1	analysis					1400:1407	glycan analysis	1393:1407	glycan analysis	1393:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	19	dep	Igs	1372:1374	arg1	Igs					1372:1374	Igs purification and glycan analysis	1372:1407	Igs purification and glycan analysis	1372:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	6	20	theme	subunits	1171:1178	arg1	level					1133:1137	the level	1129:1137	the level of free glycans, glycopeptides, subunits, or intact Igs	1129:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	6	21	theme	typical	1079:1085	arg1	workflows					1087:1095	typical workflows	1079:1095	typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs	1079:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	4	22	theme	analytical	685:694	arg1	methods					696:702	other analytical methods	679:702	other analytical methods	679:702	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	5	23	theme	analytical	780:789	arg1	approaches					791:800	analytical approaches	780:800	analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs	780:896	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	6	24	theme	LC	1019:1020	arg1	methods					1022:1028	the most often used LC methods	999:1028	the most often used LC methods for Ig purification	999:1048	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	6	25	gly	glycopeptides	1156:1168	arg2	glycopeptides					1156:1168	glycopeptides	1156:1168	glycopeptides	1156:1168	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	6	26	theme	N-	1101:1102	arg1	analysis					1117:1124	N- and O-glycan analysis	1101:1124	N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs	1101:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	3	27	theme	Igs	458:460	arg1	features					446:453	structural and functional features	420:453	structural and functional features of Igs	420:460	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	3	28	theme	therapeutic	386:396	arg1	biomolecules					398:409	therapeutic biomolecules	386:409	therapeutic biomolecules based on structural and functional features of Igs	386:460	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	8	29	theme	other	1417:1421	arg1	hand					1423:1426	the other hand	1413:1426	the other hand	1413:1426	On the other hand, lectin microarrays have found their application in the rapid screening of glycan profiles on intact proteins.
34687007	6	30	theme	glycopeptides	1156:1168	arg1	level					1133:1137	the level	1129:1137	the level of free glycans, glycopeptides, subunits, or intact Igs	1129:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	3	31	theme	functional	435:444	arg1	features					446:453	structural and functional features	420:453	structural and functional features of Igs	420:460	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	0	32	theme	Lectin	0:5	arg1	Methods					39:45	Lectin and Liquid Chromatography-Based Methods	0:45	Methods	39:45	Lectin and Liquid Chromatography-Based Methods for Immunoglobulin (G) Glycosylation Analysis.
34687007	1	33	theme	Immunoglobulin	94:107	arg1	glycosylation					114:126	Immunoglobulin (Ig) glycosylation	94:126	Immunoglobulin (Ig) glycosylation	94:126	Immunoglobulin (Ig) glycosylation has been shown to dramatically affect its structure and effector functions.
34687007	1	34	theme	effector	184:191	arg1	functions					193:201	effector functions	184:201	effector functions	184:201	Immunoglobulin (Ig) glycosylation has been shown to dramatically affect its structure and effector functions.
34687007	0	35	theme	Chromatography-Based	18:37	arg1	Methods					39:45	Lectin and Liquid Chromatography-Based Methods	0:45	Methods	39:45	Lectin and Liquid Chromatography-Based Methods for Immunoglobulin (G) Glycosylation Analysis.
34687007	6	36	theme	Igs	1191:1193	arg1	level					1133:1137	the level	1129:1137	the level of free glycans, glycopeptides, subunits, or intact Igs	1129:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	1	37	gly	glycosylation	114:126	arg1	effector					184:191	effector functions	184:201	effector functions	184:201	Immunoglobulin (Ig) glycosylation has been shown to dramatically affect its structure and effector functions.
34687007	7	38	from	tool	1364:1367	arg1	purification					1376:1387	purification	1376:1387	purification	1376:1387	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	38	from	tool	1364:1367	arg1	analysis					1400:1407	glycan analysis	1393:1407	glycan analysis	1393:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	38	from	tool	1364:1367	arg1	Igs					1372:1374	Igs purification and glycan analysis	1372:1407	Igs purification and glycan analysis	1372:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	6	39	theme	glycans	1147:1153	arg1	level					1133:1137	the level	1129:1137	the level of free glycans, glycopeptides, subunits, or intact Igs	1129:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	3	40	theme	quality	479:485	arg1	control					487:493	stringent quality control	469:493	stringent quality control	469:493	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	0	41	theme	Liquid	11:16	arg1	Methods					39:45	Lectin and Liquid Chromatography-Based Methods	0:45	Methods	39:45	Lectin and Liquid Chromatography-Based Methods for Immunoglobulin (G) Glycosylation Analysis.
34687007	6	42	theme	General	954:960	arg1	principles					962:971	General principles	954:971	General principles	954:971	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	5	43	theme	G	932:932	arg1	applications					940:951	immunoglobulin G (IgG) applications	917:951	immunoglobulin G (IgG) applications	917:951	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	4	44	theme	glycosylation	639:651	arg1	analysis					653:660	Ig glycosylation analysis	636:660	Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis	636:757	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	3	45	theme	structural	420:429	arg1	features					446:453	structural and functional features	420:453	structural and functional features of Igs	420:460	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	6	46	theme	practical	977:985	arg1	examples					987:994	practical examples	977:994	practical examples	977:994	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	7	47	theme	purification	1313:1324	arg1	analysis					1251:1258	the analysis	1247:1258	the analysis of lectin-carbohydrate interactions and glycoprotein purification	1247:1324	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	48	theme	glycoprotein	1300:1311	arg1	purification					1313:1324	glycoprotein purification	1300:1324	glycoprotein purification	1300:1324	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	5	49	theme	Igs	894:896	arg1	O-glycosylation					866:880	O-glycosylation	866:880	O-glycosylation	866:880	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	5	49	theme	Igs	894:896	arg1	N-					859:860	low- and high-throughput N-	834:860	low- and high-throughput N-	834:860	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	4	50	used	used	628:631	arg2	LC					585:586	LC	585:586	LC	585:586	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	4	50	used	used	628:631	arg2	chromatography					569:582	Liquid chromatography	562:582	Liquid chromatography (LC)	562:587	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	4	50	used	used	628:631	arg2	methods					606:612	lectin-based methods	593:612	lectin-based methods	593:612	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	5	51	theme	high-throughput	843:857	arg1	N-					859:860	low- and high-throughput N-	834:860	low- and high-throughput N-	834:860	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	3	52	theme	stringent	469:477	arg1	control					487:493	stringent quality control	469:493	stringent quality control	469:493	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	7	53	theme	interactions	1283:1294	arg1	analysis					1251:1258	the analysis	1247:1258	the analysis of lectin-carbohydrate interactions and glycoprotein purification	1247:1324	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	3	54	theme	production	506:515	arg1	process					517:523	the production process	502:523	the production process	502:523	On the other hand, therapeutic biomolecules based on structural and functional features of Igs demand stringent quality control during the production process to ensure their safety and efficacy.
34687007	0	55	theme	Immunoglobulin	51:64	arg1	Analysis					84:91	Immunoglobulin (G) Glycosylation Analysis	51:91	Immunoglobulin (G) Glycosylation Analysis	51:91	Lectin and Liquid Chromatography-Based Methods for Immunoglobulin (G) Glycosylation Analysis.
34687007	4	56	theme	Liquid	562:567	arg1	LC					585:586	LC	585:586	LC	585:586	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	4	56	theme	Liquid	562:567	arg1	chromatography					569:582	Liquid chromatography	562:582	Liquid chromatography (LC)	562:587	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	2	57	theme	glycosylation	207:219	arg1	changes					221:227	Ig glycosylation changes	204:227	Ig glycosylation changes	204:227	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	7	58	theme	Lectin	1196:1201	arg1	tool					1364:1367	a valuable tool	1353:1367	a valuable tool in Igs purification and glycan analysis	1353:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	58	theme	Lectin	1196:1201	arg1	approach					1234:1241	a historical approach	1221:1241	a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification	1221:1324	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	58	theme	Lectin	1196:1201	arg1	chromatography					1203:1216	Lectin chromatography	1196:1216	Lectin chromatography	1196:1216	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	2	59	theme	disease	346:352	arg1	advancement					354:364	disease advancement	346:364	disease advancement	346:364	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	7	60	theme	valuable	1355:1362	arg1	tool					1364:1367	a valuable tool	1353:1367	a valuable tool in Igs purification and glycan analysis	1353:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	60	theme	valuable	1355:1362	arg1	chromatography					1203:1216	Lectin chromatography	1196:1216	Lectin chromatography	1196:1216	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	4	61	theme	capillary	733:741	arg1	electrophoresis					743:757	capillary electrophoresis	733:757	capillary electrophoresis	733:757	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	2	62	theme	Ig	204:205	arg1	changes					221:227	Ig glycosylation changes	204:227	Ig glycosylation changes	204:227	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	7	63	theme	glycan	1393:1398	arg1	analysis					1400:1407	glycan analysis	1393:1407	glycan analysis	1393:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	63	theme	glycan	1393:1398	arg1	Igs					1372:1374	Igs purification and glycan analysis	1372:1407	Igs purification and glycan analysis	1372:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	8	64	from	screening	1490:1498	arg1	proteins					1529:1536	intact proteins	1522:1536	intact proteins	1522:1536	On the other hand, lectin microarrays have found their application in the rapid screening of glycan profiles on intact proteins.
34687007	7	65	used	used	1345:1348	arg2	approach					1234:1241	a historical approach	1221:1241	a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification	1221:1324	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	65	used	used	1345:1348	arg2	chromatography					1203:1216	Lectin chromatography	1196:1216	Lectin chromatography	1196:1216	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	65	used	used	1345:1348	arg2	tool					1364:1367	a valuable tool	1353:1367	a valuable tool in Igs purification and glycan analysis	1353:1407	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	8	66	theme	rapid	1484:1488	arg1	screening					1490:1498	the rapid screening	1480:1498	the rapid screening of glycan profiles on intact proteins	1480:1536	On the other hand, lectin microarrays have found their application in the rapid screening of glycan profiles on intact proteins.
34687007	4	67	dep	spectrometry	716:727	arg1	e.g.					705:708	e.g.	705:708	e.g.	705:708	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	6	68	theme	O-glycan	1108:1115	arg1	analysis					1117:1124	N- and O-glycan analysis	1101:1124	N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs	1101:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	6	69	theme	Ig	1034:1035	arg1	purification					1037:1048	Ig purification	1034:1048	Ig purification	1034:1048	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	4	70	theme	complementary	662:674	arg1	analysis					653:660	Ig glycosylation analysis	636:660	Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis	636:757	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	2	71	theme	different	255:263	arg1	diseases					265:272	different diseases	255:272	different diseases	255:272	Ig glycosylation changes have been associated with different diseases and show a promising biomarker potential for diagnosis and prognosis of disease advancement.
34687007	4	72	theme	other	679:683	arg1	methods					696:702	other analytical methods	679:702	other analytical methods	679:702	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	4	73	theme	Ig	636:637	arg1	analysis					653:660	Ig glycosylation analysis	636:660	Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis	636:757	Liquid chromatography (LC) and lectin-based methods are routinely used in Ig glycosylation analysis complementary to other analytical methods, e.g., mass spectrometry and capillary electrophoresis.
34687007	7	74	theme	historical	1223:1232	arg1	approach					1234:1241	a historical approach	1221:1241	a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification	1221:1324	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	7	74	theme	historical	1223:1232	arg1	chromatography					1203:1216	Lectin chromatography	1196:1216	Lectin chromatography	1196:1216	Lectin chromatography is a historical approach for the analysis of lectin-carbohydrate interactions and glycoprotein purification but is still being used as a valuable tool in Igs purification and glycan analysis.
34687007	6	75	theme	intact	1184:1189	arg1	Igs					1191:1193	intact Igs	1184:1193	intact Igs	1184:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	6	76	from	analysis	1117:1124	arg1	level					1133:1137	the level	1129:1137	the level of free glycans, glycopeptides, subunits, or intact Igs	1129:1193	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	5	77	theme	low-	834:837	arg1	N-					859:860	low- and high-throughput N-	834:860	low- and high-throughput N-	834:860	This chapter covers analytical approaches based on LC and lectins used in low- and high-throughput N- and O-glycosylation analysis of Igs, with the focus on immunoglobulin G (IgG) applications.
34687007	6	78	theme	methods	1022:1028	arg1	principles					962:971	General principles	954:971	General principles	954:971	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
34687007	6	78	theme	methods	1022:1028	arg1	examples					987:994	practical examples	977:994	practical examples	977:994	General principles and practical examples of the most often used LC methods for Ig purification are described, together with typical workflows for N- and O-glycan analysis on the level of free glycans, glycopeptides, subunits, or intact Igs.
32001344	7	0	theme	glycosylation	1157:1169	arg1	acids					1117:1121	amino acids 57 and 330	1111:1132	acids	1117:1121	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	0	theme	glycosylation	1157:1169	arg1	330					1130:1132	330	1130:1132	330	1130:1132	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	0	theme	glycosylation	1157:1169	arg1	sites					1171:1175	the active N-linked glycosylation sites	1137:1175	the active N-linked glycosylation sites on V3	1137:1181	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	9	1	theme	V3	1428:1429	arg1	protein					1431:1437	the V3 protein	1424:1437	the V3 protein	1424:1437	Once secreted, the V3 protein associates with hyaluronan along the cell surface and within the surrounding ECM.
32001344	1	2	theme	extracellular	126:138	arg1	ECM					148:150	ECM	148:150	ECM	148:150	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	1	2	theme	extracellular	126:138	arg1	matrix					140:145	a large extracellular matrix	118:145	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	9	3	theme	surrounding	1504:1514	arg1	ECM					1516:1518	the surrounding ECM	1500:1518	the surrounding ECM	1500:1518	Once secreted, the V3 protein associates with hyaluronan along the cell surface and within the surrounding ECM.
32001344	1	4	theme	soft	205:208	arg1	tissues					210:216	most soft tissues	200:216	most soft tissues	200:216	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	8	5	theme	region	1327:1332	arg1	portions					1303:1310	portions	1303:1310	portions of the carboxy region of the protein (G3 domain)	1303:1359	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	1	6	theme	matrix	140:145	arg1	proteoglycan					178:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	8	7	theme	carboxy	1319:1325	arg1	region					1327:1332	the carboxy region	1315:1332	the carboxy region of the protein (G3 domain)	1315:1359	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	5	8	theme	3T3	862:864	arg1	lines					871:875	stable NIH 3T3 cell lines	851:875	stable NIH 3T3 cell lines	851:875	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	5	9	theme	doxycycline-inducible	797:817	arg1	V3					823:824	doxycycline-inducible rat V3	797:824	doxycycline-inducible rat V3	797:824	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	6	10	theme	efficient	1016:1024	arg1	secretion					1026:1034	efficient secretion	1016:1034	efficient secretion	1016:1034	We further show that N-linked glycosylation is required for efficient secretion and solubility of the protein.
32001344	5	11	theme	rat	819:821	arg1	V3					823:824	doxycycline-inducible rat V3	797:824	doxycycline-inducible rat V3	797:824	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	10	12	theme	critical	1545:1552	arg1	parameters					1554:1563	critical parameters	1545:1563	critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells	1545:1646	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	0	13	theme	N-linked	82:89	arg1	glycosylation					91:103	N-linked glycosylation	82:103	N-linked glycosylation	82:103	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	5	14	theme	classical	927:935	arg1	pathway					947:953	the classical secretory pathway	923:953	the classical secretory pathway	923:953	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	7	15	link	N-linked	1148:1155	arg1	acids					1117:1121	amino acids 57 and 330	1111:1132	acids	1117:1121	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	15	link	N-linked	1148:1155	arg1	330					1130:1132	330	1130:1132	330	1130:1132	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	15	link	N-linked	1148:1155	arg1	sites					1171:1175	the active N-linked glycosylation sites	1137:1175	the active N-linked glycosylation sites on V3	1137:1181	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	16	theme	active	1141:1146	arg1	acids					1117:1121	amino acids 57 and 330	1111:1132	acids	1117:1121	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	16	theme	active	1141:1146	arg1	330					1130:1132	330	1130:1132	330	1130:1132	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	16	theme	active	1141:1146	arg1	sites					1171:1175	the active N-linked glycosylation sites	1137:1175	the active N-linked glycosylation sites on V3	1137:1181	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	5	17	theme	V3	823:824	arg1	generation					783:792	lentiviral generation	772:792	lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag	772:846	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	10	18	from	role	1666:1669	arg1	organization					1685:1696	the organization	1681:1696	the organization of hyaluronan	1681:1710	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	5	19	theme	secretory	937:945	arg1	pathway					947:953	the classical secretory pathway	923:953	the classical secretory pathway	923:953	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	6	20	link	N-linked	977:984	arg1	glycosylation					986:998	N-linked glycosylation	977:998	N-linked glycosylation	977:998	We further show that N-linked glycosylation is required for efficient secretion and solubility of the protein.
32001344	6	21	theme	N-linked	977:984	arg1	glycosylation					986:998	N-linked glycosylation	977:998	N-linked glycosylation	977:998	We further show that N-linked glycosylation is required for efficient secretion and solubility of the protein.
32001344	8	22	theme	V3	1380:1381	arg1	processing					1383:1392	V3 processing	1380:1392	V3 processing	1380:1392	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	5	23	with	generation	783:792	arg1	tag					844:846	a C-terminal tag	831:846	a C-terminal tag	831:846	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	8	24	theme	protein	1341:1347	arg1	region					1327:1332	the carboxy region	1315:1332	the carboxy region of the protein (G3 domain)	1315:1359	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	7	25	gly	glycosylation	1157:1169	arg2	330					1130:1132	330	1130:1132	330	1130:1132	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	25	gly	glycosylation	1157:1169	arg2	acids					1117:1121	amino acids 57 and 330	1111:1132	acids	1117:1121	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	25	gly	glycosylation	1157:1169	arg2	sites					1171:1175	the active N-linked glycosylation sites	1137:1175	the active N-linked glycosylation sites on V3	1137:1181	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	26	theme	N-linked	1148:1155	arg1	acids					1117:1121	amino acids 57 and 330	1111:1132	acids	1117:1121	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	26	theme	N-linked	1148:1155	arg1	330					1130:1132	330	1130:1132	330	1130:1132	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	26	theme	N-linked	1148:1155	arg1	sites					1171:1175	the active N-linked glycosylation sites	1137:1175	the active N-linked glycosylation sites on V3	1137:1181	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	9	27	theme	cell	1476:1479	arg1	surface					1481:1487	the cell surface	1472:1487	the cell surface	1472:1487	Once secreted, the V3 protein associates with hyaluronan along the cell surface and within the surrounding ECM.
32001344	5	28	theme	lentiviral	772:781	arg1	generation					783:792	lentiviral generation	772:792	lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag	772:846	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	1	29	theme	chondroitin	153:163	arg1	proteoglycan					178:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	2	30	theme	alternative	322:332	arg1	splicing					334:341	alternative splicing	322:341	alternative splicing	322:341	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	8	31	theme	G3	1350:1351	arg1	protein					1341:1347	the protein	1337:1347	the protein (G3 domain)	1337:1359	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	8	31	theme	G3	1350:1351	arg1	domain					1353:1358	G3 domain	1350:1358	G3 domain	1350:1358	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	4	32	from	transcript	614:623	arg1	number					649:654	a number	647:654	a number of tissues	647:665	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	2	33	dep	isoforms	274:281	arg1	isoforms					274:281	At least four major isoforms	254:281	At least four major isoforms (V0, V1, V2, and V3)	254:302	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	2	33	dep	isoforms	274:281	arg1	V2					292:293	V2	292:293	V2	292:293	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	2	33	dep	isoforms	274:281	arg1	V3					300:301	V3	300:301	V3	300:301	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	2	33	dep	isoforms	274:281	arg1	V1					288:289	V1	288:289	V1	288:289	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	5	34	theme	stable	851:856	arg1	lines					871:875	stable NIH 3T3 cell lines	851:875	stable NIH 3T3 cell lines	851:875	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	1	35	theme	sulfate	165:171	arg1	proteoglycan					178:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	4	36	dep	synthesis	694:702	arg1	the					690:692	the	690:692	the	690:692	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	3	37	theme	various	401:407	arg1	tissues					409:415	various tissues	401:415	various tissues	401:415	The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions.
32001344	8	38	dep	exons	1275:1279	arg1	11-13					1281:1285	11-13	1281:1285	11-13	1281:1285	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	3	39	theme	versican	360:367	arg1	isoforms					348:355	The isoforms	344:355	The isoforms of versican	344:367	The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions.
32001344	0	40	theme	versican	31:38	arg1	isoform					40:46	versican isoform V3	31:49	versican isoform V3	31:49	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	4	41	theme	several	573:579	arg1	studies					581:587	several studies	573:587	several studies	573:587	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	1	42	located	found	191:195	arg1	tissues					210:216	most soft tissues	200:216	most soft tissues	200:216	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	1	42	located	found	191:195	arg2	proteoglycan					178:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	5	43	used	used	767:770	arg2	we					764:765	we	764:765	we	764:765	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	1	44	theme	CS	174:175	arg1	proteoglycan					178:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	1	45	theme	VCAN	243:246	arg1	gene					248:251	the VCAN gene	239:251	the VCAN gene	239:251	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	10	46	theme	mammalian	1632:1640	arg1	cells					1642:1646	mammalian cells	1632:1646	mammalian cells	1632:1646	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	3	47	theme	cell	489:492	arg1	growth					494:499	cell growth	489:499	cell growth	489:499	The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions.
32001344	7	48	theme	cell	1206:1209	arg1	type					1211:1214	this cell type	1201:1214	this cell type	1201:1214	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	9	49	dep	secreted	1414:1421	arg1	Once					1409:1412	Once	1409:1412	Once	1409:1412	Once secreted, the V3 protein associates with hyaluronan along the cell surface and within the surrounding ECM.
32001344	10	50	theme	V3	1618:1619	arg1	isoform					1621:1627	the V3 isoform	1614:1627	the V3 isoform	1614:1627	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	4	51	theme	protein	740:746	arg1	secretion					705:713	secretion	705:713	secretion	705:713	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	4	51	theme	protein	740:746	arg1	targeting					720:728	targeting	720:728	targeting	720:728	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	4	51	theme	protein	740:746	arg1	synthesis					694:702	synthesis	694:702	synthesis	694:702	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	3	52	theme	immune	520:525	arg1	regulation					527:536	immune regulation	520:536	immune regulation	520:536	The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions.
32001344	3	53	theme	ECM	474:476	arg1	structure					478:486	ECM structure	474:486	ECM structure	474:486	The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions.
32001344	10	54	theme	hyaluronan	1701:1710	arg1	organization					1685:1696	the organization	1681:1696	the organization of hyaluronan	1681:1710	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	0	55	theme	isoform	40:46	arg1	secretion					18:26	secretion	18:26	secretion	18:26	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	0	55	theme	isoform	40:46	arg1	synthesis					4:12	synthesis	4:12	synthesis	4:12	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	8	56	theme	deletion	1235:1242	arg1	constructs					1244:1253	exon deletion constructs	1230:1253	exon deletion constructs of V3	1230:1259	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	4	57	theme	V3	737:738	arg1	protein					740:746	the V3 protein	733:746	the V3 protein	733:746	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	3	58	theme	many	551:554	arg1	functions					556:564	their many functions	545:564	their many functions	545:564	The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions.
32001344	5	59	theme	cell	866:869	arg1	lines					871:875	stable NIH 3T3 cell lines	851:875	stable NIH 3T3 cell lines	851:875	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	2	60	theme	major	268:272	arg1	isoforms					274:281	At least four major isoforms	254:281	At least four major isoforms (V0, V1, V2, and V3)	254:302	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	2	60	theme	major	268:272	arg1	V2					292:293	V2	292:293	V2	292:293	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	2	60	theme	major	268:272	arg1	V3					300:301	V3	300:301	V3	300:301	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	2	60	theme	major	268:272	arg1	V1					288:289	V1	288:289	V1	288:289	At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing.
32001344	6	61	theme	protein	1058:1064	arg1	solubility					1040:1049	solubility	1040:1049	solubility	1040:1049	We further show that N-linked glycosylation is required for efficient secretion and solubility of the protein.
32001344	6	61	theme	protein	1058:1064	arg1	secretion					1026:1034	efficient secretion	1016:1034	efficient secretion	1016:1034	We further show that N-linked glycosylation is required for efficient secretion and solubility of the protein.
32001344	10	62	theme	isoform	1621:1627	arg1	solubility					1585:1594	solubility	1585:1594	solubility	1585:1594	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	10	62	theme	isoform	1621:1627	arg1	targeting					1601:1609	targeting	1601:1609	targeting	1601:1609	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	10	62	theme	isoform	1621:1627	arg1	processing					1573:1582	processing	1573:1582	processing	1573:1582	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	4	63	theme	tissues	659:665	arg1	number					649:654	a number	647:654	a number of tissues	647:665	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	5	64	theme	NIH	858:860	arg1	lines					871:875	stable NIH 3T3 cell lines	851:875	stable NIH 3T3 cell lines	851:875	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	4	65	theme	mRNA	609:612	arg1	transcript					614:623	the mRNA transcript	605:623	the mRNA transcript for the V3 isoform in a number of tissues	605:665	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	4	66	theme	V3	633:634	arg1	isoform					636:642	the V3 isoform	629:642	the V3 isoform	629:642	While several studies have identified the mRNA transcript for the V3 isoform in a number of tissues, little is known about the synthesis, secretion, and targeting of the V3 protein.
32001344	6	67	gly	glycosylation	986:998	arg1	protein					1058:1064	the protein	1054:1064	the protein	1054:1064	We further show that N-linked glycosylation is required for efficient secretion and solubility of the protein.
32001344	5	68	theme	C-terminal	833:842	arg1	tag					844:846	a C-terminal tag	831:846	a C-terminal tag	831:846	In this study, we used lentiviral generation of doxycycline-inducible rat V3 with a C-terminal tag in stable NIH 3T3 cell lines and demonstrated that V3 is processed through the classical secretory pathway.
32001344	0	69	link	N-linked	82:89	arg1	glycosylation					91:103	N-linked glycosylation	82:103	N-linked glycosylation	82:103	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	10	70	dep	processing	1573:1582	arg1	the					1569:1571	the	1569:1571	the	1569:1571	These results establish critical parameters for the processing, solubility, and targeting of the V3 isoform by mammalian cells and establishes a role for V3 in the organization of hyaluronan.
32001344	7	71	theme	amino	1111:1115	arg1	acids					1117:1121	amino acids 57 and 330	1111:1132	acids	1117:1121	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	71	theme	amino	1111:1115	arg1	330					1130:1132	330	1130:1132	330	1130:1132	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	7	71	theme	amino	1111:1115	arg1	sites					1171:1175	the active N-linked glycosylation sites	1137:1175	the active N-linked glycosylation sites on V3	1137:1181	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	0	72	theme	mammalian	54:62	arg1	cells					64:68	mammalian cells	54:68	mammalian cells	54:68	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	0	73	dep	synthesis	4:12	arg1	role					73:76	A role	71:76	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.	0:104	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	0	73	dep	synthesis	4:12	arg1	The					0:2	The	0:2	The	0:2	The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.
32001344	8	74	theme	exon	1230:1233	arg1	constructs					1244:1253	exon deletion constructs	1230:1253	exon deletion constructs of V3	1230:1259	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	7	75	theme	site-directed	1070:1082	arg1	mutagenesis					1084:1094	site-directed mutagenesis	1070:1094	site-directed mutagenesis	1070:1094	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	8	76	theme	V3	1258:1259	arg1	constructs					1244:1253	exon deletion constructs	1230:1253	exon deletion constructs of V3	1230:1259	Furthermore, exon deletion constructs of V3 revealed that exons 11-13, which code for portions of the carboxy region of the protein (G3 domain), are essential for V3 processing and secretion.
32001344	7	77	from	sites	1171:1175	arg1	V3					1180:1181	V3	1180:1181	V3	1180:1181	By site-directed mutagenesis, we identified amino acids 57 and 330 as the active N-linked glycosylation sites on V3 when expressed in this cell type.
32001344	1	78	theme	large	120:124	arg1	ECM					148:150	ECM	148:150	ECM	148:150	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	1	78	theme	large	120:124	arg1	matrix					140:145	a large extracellular matrix	118:145	a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan	118:189	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
32001344	1	79	theme	most	200:203	arg1	tissues					210:216	most soft tissues	200:216	most soft tissues	200:216	Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene.
34520098	2	0	theme	oxocarbenium	470:481	arg1	intermediate					487:498	the oxocarbenium ion intermediate	466:498	the oxocarbenium ion intermediate	466:498	Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate.
34520098	5	1	theme	neuraminidase	785:797	arg1	recognition					799:809	H1N1 neuraminidase recognition	780:809	H1N1 neuraminidase recognition	780:809	The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition.
34520098	7	2	theme	hinderance	1023:1032	arg1	effects					988:994	the effects	984:994	the effects of multivalency and steric hinderance	984:1032	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	5	3	theme	recognition	799:809	arg1	basis					771:775	the molecular basis	757:775	the molecular basis of H1N1 neuraminidase recognition	757:809	The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition.
34520098	7	4	theme	multivalency	999:1010	arg1	effects					988:994	the effects	984:994	the effects of multivalency and steric hinderance	984:1032	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	6	5	theme	sialic	896:901	arg1	acid					903:906	sialic acid	896:906	sialic acid	896:906	The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch.
34520098	6	6	from	branch	916:921	arg1	difference					863:872	a difference	861:872	a difference in the recognition of sialic acid on each branch	861:921	The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch.
34520098	3	7	theme	glycosylation	542:554	arg1	reactions					556:564	these glycosylation reactions	536:564	these glycosylation reactions	536:564	Furthermore, high α-selectivity of these glycosylation reactions was realized by utilizing remote participation.
34520098	5	8	theme	molecular	761:769	arg1	basis					771:775	the molecular basis	757:775	the molecular basis of H1N1 neuraminidase recognition	757:809	The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition.
34520098	4	9	theme	sialyl	651:656	arg1	N-glycans					658:666	Two asymmetrically deuterium labeled sialyl N-glycans	614:666	Two asymmetrically deuterium labeled sialyl N-glycans	614:666	Two asymmetrically deuterium labeled sialyl N-glycans were also synthesized by the same strategy.
34520098	6	10	from	difference	863:872	arg1	recognition					881:891	the recognition	877:891	the recognition of sialic acid on each branch	877:921	The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch.
34520098	6	10	from	difference	863:872	arg1	branch					916:921	each branch	911:921	each branch	911:921	The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch.
34520098	6	11	from	recognition	881:891	arg1	branch					916:921	each branch	911:921	each branch	911:921	The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch.
34520098	6	12	theme	deuterated	831:840	arg1	N-glycans					842:850	The asymmetrically deuterated N-glycans	812:850	The asymmetrically deuterated N-glycans	812:850	The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch.
34520098	2	13	theme	branched	372:379	arg1	mannose					381:387	the branched mannose	368:387	the branched mannose	368:387	Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate.
34520098	3	14	theme	high	514:517	arg1	α-selectivity					519:531	high α-selectivity	514:531	high α-selectivity of these glycosylation reactions	514:564	Furthermore, high α-selectivity of these glycosylation reactions was realized by utilizing remote participation.
34520098	4	15	theme	same	697:700	arg1	strategy					702:709	the same strategy	693:709	the same strategy	693:709	Two asymmetrically deuterium labeled sialyl N-glycans were also synthesized by the same strategy.
34520098	0	16	theme	Chemical	0:7	arg1	Synthesis					9:17	Chemical Synthesis	0:17	Chemical Synthesis of Sialyl N-Glycans	0:37	Chemical Synthesis of Sialyl N-Glycans and Analysis of Their Recognition by Neuraminidase.
34520098	2	17	from	glycosylation	351:363	arg1	solvent					401:407	an ether solvent	392:407	an ether solvent	392:407	Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate.
34520098	1	18	theme	first	186:190	arg1	time					192:195	the first time	182:195	the first time	182:195	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	0	19	theme	Sialyl	22:27	arg1	N-Glycans					29:37	Sialyl N-Glycans	22:37	Sialyl N-Glycans	22:37	Chemical Synthesis of Sialyl N-Glycans and Analysis of Their Recognition by Neuraminidase.
34520098	3	20	theme	reactions	556:564	arg1	α-selectivity					519:531	high α-selectivity	514:531	high α-selectivity of these glycosylation reactions	514:564	Furthermore, high α-selectivity of these glycosylation reactions was realized by utilizing remote participation.
34520098	7	21	used	used	967:970	arg2	N-glycan					954:961	the tetraantennary N-glycan	935:961	the tetraantennary N-glycan	935:961	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	7	21	used	used	967:970	arg2	Meanwhile					924:932	Meanwhile	924:932	Meanwhile	924:932	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	2	22	gly	glycosylation	351:363	arg1	solvent					401:407	an ether solvent	392:407	an ether solvent	392:407	Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate.
34520098	2	23	theme	ether	395:399	arg1	solvent					401:407	an ether solvent	392:407	an ether solvent	392:407	Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate.
34520098	1	24	gly	sialylated	125:134	arg1	N-glycan					151:158	a fully sialylated tetraantennary N-glycan	117:158	a fully sialylated tetraantennary N-glycan	117:158	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	0	25	theme	N-Glycans	29:37	arg1	Analysis					43:50	Analysis	43:50	Analysis of Their Recognition by Neuraminidase	43:88	Chemical Synthesis of Sialyl N-Glycans and Analysis of Their Recognition by Neuraminidase.
34520098	0	25	theme	N-Glycans	29:37	arg1	Synthesis					9:17	Chemical Synthesis	0:17	Chemical Synthesis of Sialyl N-Glycans	0:37	Chemical Synthesis of Sialyl N-Glycans and Analysis of Their Recognition by Neuraminidase.
34520098	5	26	used	used	743:746	arg2	N-glycans					728:736	The synthesized N-glycans	712:736	The synthesized N-glycans	712:736	The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition.
34520098	6	27	theme	acid	903:906	arg1	recognition					881:891	the recognition	877:891	the recognition of sialic acid on each branch	877:921	The asymmetrically deuterated N-glycans revealed a difference in the recognition of sialic acid on each branch.
34520098	5	28	theme	H1N1	780:783	arg1	recognition					799:809	H1N1 neuraminidase recognition	780:809	H1N1 neuraminidase recognition	780:809	The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition.
34520098	2	29	theme	desired	429:435	arg1	glycosylation					437:449	the desired glycosylation	425:449	the desired glycosylation	425:449	Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate.
34520098	4	30	dep	labeled	643:649	arg1	deuterium					633:641	deuterium	633:641	deuterium	633:641	Two asymmetrically deuterium labeled sialyl N-glycans were also synthesized by the same strategy.
34520098	3	31	theme	remote	592:597	arg1	participation					599:611	remote participation	592:611	remote participation	592:611	Furthermore, high α-selectivity of these glycosylation reactions was realized by utilizing remote participation.
34520098	7	32	theme	branching	1045:1053	arg1	structures					1055:1064	branching structures	1045:1064	branching structures	1045:1064	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	1	33	theme	intermolecular	300:313	arg1	bonds					324:328	intermolecular hydrogen bonds	300:328	intermolecular hydrogen bonds	300:328	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	1	34	theme	chemical	95:102	arg1	synthesis					104:112	The chemical synthesis	91:112	The chemical synthesis of a fully sialylated tetraantennary N-glycan	91:158	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	1	35	theme	diacetyl	210:217	arg1	strategy					219:226	the diacetyl strategy	206:226	the diacetyl strategy	206:226	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	5	36	theme	synthesized	716:726	arg1	N-glycans					728:736	The synthesized N-glycans	712:736	The synthesized N-glycans	712:736	The synthesized N-glycans were used to probe the molecular basis of H1N1 neuraminidase recognition.
34520098	1	37	theme	sialylated	125:134	arg1	N-glycan					151:158	a fully sialylated tetraantennary N-glycan	117:158	a fully sialylated tetraantennary N-glycan	117:158	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	0	38	theme	Recognition	61:71	arg1	Analysis					43:50	Analysis	43:50	Analysis of Their Recognition by Neuraminidase	43:88	Chemical Synthesis of Sialyl N-Glycans and Analysis of Their Recognition by Neuraminidase.
34520098	0	38	theme	Recognition	61:71	arg1	Synthesis					9:17	Chemical Synthesis	0:17	Chemical Synthesis of Sialyl N-Glycans	0:37	Chemical Synthesis of Sialyl N-Glycans and Analysis of Their Recognition by Neuraminidase.
34520098	1	39	theme	tetraantennary	136:149	arg1	N-glycan					151:158	a fully sialylated tetraantennary N-glycan	117:158	a fully sialylated tetraantennary N-glycan	117:158	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	7	40	theme	tetraantennary	939:952	arg1	Meanwhile					924:932	Meanwhile	924:932	Meanwhile	924:932	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	7	40	theme	tetraantennary	939:952	arg1	N-glycan					954:961	the tetraantennary N-glycan	935:961	the tetraantennary N-glycan	935:961	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	4	41	theme	labeled	643:649	arg1	N-glycans					658:666	Two asymmetrically deuterium labeled sialyl N-glycans	614:666	Two asymmetrically deuterium labeled sialyl N-glycans	614:666	Two asymmetrically deuterium labeled sialyl N-glycans were also synthesized by the same strategy.
34520098	2	42	theme	ion	483:485	arg1	intermediate					487:498	the oxocarbenium ion intermediate	466:498	the oxocarbenium ion intermediate	466:498	Another key was the glycosylation to the branched mannose in an ether solvent, which promoted the desired glycosylation by stabilizing the oxocarbenium ion intermediate.
34520098	1	43	theme	hydrogen	315:322	arg1	bonds					324:328	intermolecular hydrogen bonds	300:328	intermolecular hydrogen bonds	300:328	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
34520098	7	44	theme	steric	1016:1021	arg1	hinderance					1023:1032	steric hinderance	1016:1032	steric hinderance	1016:1032	Meanwhile, the tetraantennary N-glycan was used to evaluate the effects of multivalency and steric hinderance by forming branching structures.
34520098	1	45	theme	N-glycan	151:158	arg1	synthesis					104:112	The chemical synthesis	91:112	The chemical synthesis of a fully sialylated tetraantennary N-glycan	91:158	The chemical synthesis of a fully sialylated tetraantennary N-glycan has been achieved for the first time by using the diacetyl strategy, in which NHAc is protected as NAc2 to improve reactivity by preventing intermolecular hydrogen bonds.
33404348	3	0	with	genomics	458:465	arg1	exploration					510:520	relatively little exploration	492:520	relatively little exploration of the glycan alterations	492:546	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	6	1	theme	great	1065:1069	arg1	potential					1071:1079	great potential	1065:1079	great potential for better diagnostic markers	1065:1109	Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers.
33404348	4	2	theme	magnitude	702:710	arg1	orders					692:697	several orders	684:697	several orders of magnitude	684:710	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
33404348	0	3	from	Repertoire	4:13	arg1	Cancers					64:70	Human Cancers	58:70	Human Cancers	58:70	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	2	4	theme	tumorigenesis	312:324	arg1	features					300:307	common features	293:307	common features of tumorigenesis	293:324	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	2	4	theme	tumorigenesis	312:324	arg1	alterations					179:189	the alterations	175:189	the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation)	175:287	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	7	5	theme	associated	1230:1239	arg1	technologies					1241:1252	associated technologies	1230:1252	associated technologies	1230:1252	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	3	6	with	transcriptomics	471:485	arg1	exploration					510:520	relatively little exploration	492:520	relatively little exploration of the glycan alterations	492:546	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	7	7	theme	glycan	1394:1399	arg1	research					1401:1408	glycan research	1394:1408	glycan research	1394:1408	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	4	8	theme	dynamic	748:754	arg1	biomarkers					756:765	highly dynamic biomarkers	741:765	highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy	741:832	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
33404348	3	9	with	biomarkers	565:574	arg1	exploration					510:520	relatively little exploration	492:520	relatively little exploration of the glycan alterations	492:546	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	7	10	theme	personalized	1476:1487	arg1	medicine					1489:1496	personalized medicine	1476:1496	the personalized medicine strategies for cancer	1472:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	5	11	theme	efficient	964:972	arg1	stratification					982:995	more efficient patient stratification	959:995	more efficient patient stratification	959:995	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	2	12	from	alterations	179:189	arg1	compositions					205:216	the glycan compositions	194:216	the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation)	194:287	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	5	13	theme	environmental	908:920	arg1	factors					922:928	past and present environmental factors	891:928	past and present environmental factors	891:928	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	4	14	gly	glycosylation	617:629	arg1	proteins					634:641	proteins	634:641	proteins	634:641	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
33404348	3	15	theme	cancer	425:430	arg1	studies					432:438	cancer studies	425:438	cancer studies	425:438	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	5	16	theme	patient	974:980	arg1	stratification					982:995	more efficient patient stratification	959:995	more efficient patient stratification	959:995	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	5	17	theme	genetic	867:873	arg1	background					875:884	our genetic background	863:884	our genetic background with past and present environmental factors	863:928	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	4	18	theme	structural	659:668	arg1	complexity					670:679	their structural complexity	653:679	their structural complexity	653:679	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
33404348	5	19	theme	present	900:906	arg1	factors					922:928	past and present environmental factors	891:928	past and present environmental factors	891:928	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	6	20	theme	efficient	1138:1146	arg1	strategies					1158:1167	more efficient treatment strategies	1133:1167	more efficient treatment strategies	1133:1167	Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers.
33404348	3	21	theme	little	503:508	arg1	exploration					510:520	relatively little exploration	492:520	relatively little exploration of the glycan alterations	492:546	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	7	22	from	status	1384:1389	arg1	scope					1463:1467	the scope	1459:1467	the scope of the personalized medicine strategies for cancer	1459:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	6	23	theme	diagnostic	1092:1101	arg1	markers					1103:1109	better diagnostic markers	1085:1109	better diagnostic markers	1085:1109	Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers.
33404348	7	24	theme	high-throughput	1295:1309	arg1	profiling					1311:1319	a high-throughput profiling	1293:1319	a high-throughput profiling of glycan diversity	1293:1339	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	3	25	theme	alterations	536:546	arg1	exploration					510:520	relatively little exploration	492:520	relatively little exploration of the glycan alterations	492:546	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	7	26	theme	medicine	1489:1496	arg1	strategies					1498:1507	the personalized medicine strategies	1472:1507	the personalized medicine strategies for cancer	1472:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	2	27	theme	emerging	348:355	arg1	field					357:361	an emerging field	345:361	an emerging field examining the structure and function of glycans	345:409	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	7	28	theme	strategies	1498:1507	arg1	scope					1463:1467	the scope	1459:1467	the scope of the personalized medicine strategies for cancer	1459:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	0	29	theme	Glycan	18:23	arg1	Alterations					25:35	Glycan Alterations	18:35	Glycan Alterations	18:35	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	2	30	theme	glycans	403:409	arg1	structure					377:385	structure	377:385	structure	377:385	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	2	30	theme	glycans	403:409	arg1	function					391:398	function	391:398	function	391:398	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	1	31	theme	leading	87:93	arg1	cause					95:99	the leading cause	83:99	the leading cause of death worldwide	83:118	Cancer as the leading cause of death worldwide has many issues that still need to be addressed.
33404348	7	32	from	research	1401:1408	arg1	scope					1463:1467	the scope	1459:1467	the scope of the personalized medicine strategies for cancer	1459:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	7	33	theme	recent	1193:1198	arg1	developments					1200:1211	recent developments	1193:1211	recent developments in glycomics and associated technologies	1193:1252	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	7	34	theme	glycans	1448:1454	arg1	research					1401:1408	glycan research	1394:1408	glycan research	1394:1408	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	7	34	theme	glycans	1448:1454	arg1	applications					1428:1439	the potential applications	1414:1439	the potential applications of the glycans in the scope of the personalized medicine strategies for cancer	1414:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	3	35	theme	glycan	529:534	arg1	alterations					536:546	the glycan alterations	525:546	the glycan alterations	525:546	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	2	36	dep	glycosylation	243:255	arg1	i.e.					237:240	i.e.	237:240	i.e.	237:240	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	6	37	theme	treatment	1148:1156	arg1	strategies					1158:1167	more efficient treatment strategies	1133:1167	more efficient treatment strategies	1133:1167	Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers.
33404348	2	38	dep	structure	377:385	arg1	the					373:375	the	373:375	the	373:375	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	2	39	dep	compositions	205:216	arg1	structures					225:234	or/and structures	218:234	the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation)	194:287	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	0	40	theme	Alterations	25:35	arg1	Glycoproteins					41:53	Glycoproteins	41:53	Glycoproteins	41:53	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	0	40	theme	Alterations	25:35	arg1	Repertoire					4:13	The Repertoire	0:13	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers	0:70	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	0	40	theme	Alterations	25:35	arg1	Alterations					25:35	Glycan Alterations	18:35	Glycan Alterations	18:35	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	7	41	theme	potential	1418:1426	arg1	applications					1428:1439	the potential applications	1414:1439	the potential applications of the glycans in the scope of the personalized medicine strategies for cancer	1414:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	2	42	theme	glycan	198:203	arg1	compositions					205:216	the glycan compositions	194:216	the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation)	194:287	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	3	43	gly	glycoprotein	552:563	arg1	glycoprotein					552:563	glycoprotein biomarkers	552:574	glycoprotein biomarkers among individuals and populations	552:608	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	7	44	from	scope	1463:1467	arg1	status					1384:1389	the current status	1372:1389	the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer	1372:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	3	45	theme	glycoprotein	552:563	arg1	biomarkers					565:574	glycoprotein biomarkers	552:574	glycoprotein biomarkers among individuals and populations	552:608	In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations.
33404348	7	46	from	developments	1200:1211	arg1	glycomics					1216:1224	glycomics	1216:1224	glycomics	1216:1224	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	7	46	from	developments	1200:1211	arg1	technologies					1241:1252	associated technologies	1230:1252	associated technologies	1230:1252	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	4	47	theme	glycome	713:719	arg1	studies					721:727	glycome studies	713:727	glycome studies	713:727	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
33404348	0	48	theme	Glycoproteins	41:53	arg1	Glycoproteins					41:53	Glycoproteins	41:53	Glycoproteins	41:53	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	0	48	theme	Glycoproteins	41:53	arg1	Repertoire					4:13	The Repertoire	0:13	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers	0:70	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	0	48	theme	Glycoproteins	41:53	arg1	Alterations					25:35	Glycan Alterations	18:35	Glycan Alterations	18:35	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	5	49	with	background	875:884	arg1	factors					922:928	past and present environmental factors	891:928	past and present environmental factors	891:928	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	7	50	theme	research	1401:1408	arg1	status					1384:1389	the current status	1372:1389	the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer	1372:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	7	51	theme	glycan	1324:1329	arg1	diversity					1331:1339	glycan diversity	1324:1339	glycan diversity	1324:1339	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	1	52	theme	death	104:108	arg1	worldwide					110:118	death worldwide	104:118	death worldwide	104:118	Cancer as the leading cause of death worldwide has many issues that still need to be addressed.
33404348	7	53	theme	current	1376:1382	arg1	status					1384:1389	the current status	1372:1389	the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer	1372:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	7	54	theme	status	1384:1389	arg1	overview					1360:1367	an overview	1357:1367	an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer	1357:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	4	55	theme	cancer	793:798	arg1	diagnosis					800:808	cancer diagnosis	793:808	cancer diagnosis	793:808	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
33404348	2	56	theme	common	293:298	arg1	features					300:307	common features	293:307	common features of tumorigenesis	293:324	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	2	56	theme	common	293:298	arg1	alterations					179:189	the alterations	175:189	the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation)	175:287	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	6	57	theme	human	1172:1176	arg1	cancers					1178:1184	human cancers	1172:1184	human cancers	1172:1184	Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers.
33404348	7	58	theme	applications	1428:1439	arg1	status					1384:1389	the current status	1372:1389	the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer	1372:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	5	59	theme	stratification	982:995	arg1	promise					948:954	a promise	946:954	a promise of more efficient patient stratification	946:995	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	7	60	theme	diversity	1331:1339	arg1	profiling					1311:1319	a high-throughput profiling	1293:1319	a high-throughput profiling of glycan diversity	1293:1339	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	5	61	theme	past	891:894	arg1	factors					922:928	past and present environmental factors	891:928	past and present environmental factors	891:928	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	1	62	theme	worldwide	110:118	arg1	cause					95:99	the leading cause	83:99	the leading cause of death worldwide	83:118	Cancer as the leading cause of death worldwide has many issues that still need to be addressed.
33404348	7	63	theme	new	1264:1266	arg1	possibilities					1268:1280	new possibilities	1264:1280	new possibilities	1264:1280	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	4	64	theme	proteins	634:641	arg1	glycosylation					617:629	glycosylation	617:629	glycosylation of proteins	617:641	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
33404348	5	65	theme	genetic	1011:1017	arg1	variations					1019:1028	genetic variations	1011:1028	genetic variations	1011:1028	Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations.
33404348	1	66	theme	many	124:127	arg1	issues					129:134	many issues	124:134	many issues that still need to be addressed	124:166	Cancer as the leading cause of death worldwide has many issues that still need to be addressed.
33404348	7	67	from	applications	1428:1439	arg1	scope					1463:1467	the scope	1459:1467	the scope of the personalized medicine strategies for cancer	1459:1518	While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
33404348	0	68	theme	Human	58:62	arg1	Cancers					64:70	Human Cancers	58:70	Human Cancers	58:70	The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers.
33404348	1	69	contain	has	120:122	arg2	issues					129:134	many issues	124:134	many issues that still need to be addressed	124:166	Cancer as the leading cause of death worldwide has many issues that still need to be addressed.
33404348	1	69	contain	has	120:122	arg1	Cancer					73:78	Cancer	73:78	Cancer as the leading cause of death worldwide	73:118	Cancer as the leading cause of death worldwide has many issues that still need to be addressed.
33404348	2	70	theme	or/and	218:223	arg1	structures					225:234	or/and structures	218:234	the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation)	194:287	Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans.
33404348	4	71	theme	several	684:690	arg1	orders					692:697	several orders	684:697	several orders of magnitude	684:710	Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy.
32809822	0	0	theme	Imaging	68:74	arg1	Spectrometry					81:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	4	1	theme	washes	703:708	arg1	series					693:698	a series	691:698	a series of washes	691:708	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
32809822	2	2	theme	multiple	349:356	arg1	steps					369:373	multiple processing steps	349:373	multiple processing steps	349:373	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	6	3	from	obese	1183:1187	arg1	set					1167:1169	a small pooled serum set	1146:1169	a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion	1146:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	0	4	theme	Slide-Based	56:66	arg1	Spectrometry					81:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	1	5	theme	N-glycans	146:154	arg1	compositions					130:141	compositions	130:141	compositions	130:141	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	5	theme	N-glycans	146:154	arg1	levels					119:124	levels	119:124	levels	119:124	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	6	theme	many	244:247	arg1	cohorts					271:277	many large clinical sample cohorts	244:277	many large clinical sample cohorts	244:277	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	7	7	theme	clinical	1414:1421	arg1	diagnostics					1423:1433	clinical diagnostics	1414:1433	clinical diagnostics	1414:1433	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	5	8	theme	endoglycosidase	937:951	arg1	F3					953:954	endoglycosidase F3	937:954	endoglycosidase F3	937:954	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	1	9	theme	large	249:253	arg1	cohorts					271:277	many large clinical sample cohorts	244:277	many large clinical sample cohorts	244:277	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	0	10	theme	Mass	76:79	arg1	Spectrometry					81:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	0	11	dep	Workflow	94:101	arg1	Profiling					15:23	Rapid N-Glycan Profiling	0:23	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry	0:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	1	12	dep	levels	119:124	arg1	the					115:117	the	115:117	the	115:117	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	13	theme	clinical	255:262	arg1	cohorts					271:277	many large clinical sample cohorts	244:277	many large clinical sample cohorts	244:277	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	5	14	theme	structural	1095:1104	arg1	information					1106:1116	structural information	1095:1116	structural information	1095:1116	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	1	15	gly	glycoproteins	187:199	arg1	glycoproteins					187:199	glycoproteins	187:199	glycoproteins	187:199	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	7	16	theme	potential	1389:1397	arg1	application					1399:1409	potential application	1389:1409	potential application to clinical diagnostics	1389:1433	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	5	17	dep	h.	920:921	arg1	applied					960:966	applied	960:966	was applied to this workflow to identify core-fucosylated N-glycans	956:1022	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	5	17	dep	h.	920:921	arg1	displayed					1028:1036	displayed	1028:1036	displayed the adaptability of this method for the determination of structural information	1028:1116	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	2	18	theme	standard	448:455	arg1	potential					427:435	their potential	421:435	their potential for use	421:443	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	2	18	theme	standard	448:455	arg1	assays					477:482	standard clinical diagnostic assays	448:482	standard clinical diagnostic assays	448:482	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	5	19	theme	serum	897:901	arg1	microliter					883:892	one microliter	879:892	one microliter of serum	879:901	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	6	20	theme	benign	1238:1243	arg1	lesion					1245:1250	a benign lesion	1236:1250	a benign lesion	1236:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	5	21	gly	core-fucosylated	997:1012	arg1	N-glycans					1014:1022	core-fucosylated N-glycans	997:1022	core-fucosylated N-glycans	997:1022	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	2	22	theme	limited	384:390	arg1	throughput					392:401	limited throughput	384:401	limited throughput	384:401	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	0	23	theme	N-Glycan	6:13	arg1	Profiling					15:23	Rapid N-Glycan Profiling	0:23	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry	0:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	6	24	theme	pooled	1154:1159	arg1	set					1167:1169	a small pooled serum set	1146:1169	a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion	1146:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	0	25	theme	Rapid	0:4	arg1	Profiling					15:23	Rapid N-Glycan Profiling	0:23	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry	0:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	1	26	theme	sample	264:269	arg1	cohorts					271:277	many large clinical sample cohorts	244:277	many large clinical sample cohorts	244:277	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	27	from	Changes	104:110	arg1	compositions					130:141	compositions	130:141	compositions	130:141	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	27	from	Changes	104:110	arg1	levels					119:124	levels	119:124	levels	119:124	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	2	28	theme	N-glycan	296:303	arg1	profiling					305:313	N-glycan profiling	296:313	N-glycan profiling	296:313	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	2	29	contain	have	379:382	arg1	Assays					280:285	Assays	280:285	Assays used for N-glycan profiling in these fluids	280:329	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	2	29	contain	have	379:382	arg2	throughput					392:401	limited throughput	384:401	limited throughput	384:401	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	4	30	theme	N-glycosidase	732:744	arg1	F					746:746	peptide N-glycosidase F	724:746	peptide N-glycosidase F	724:746	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
32809822	5	31	theme	core-fucosylated	997:1012	arg1	N-glycans					1014:1022	core-fucosylated N-glycans	997:1022	core-fucosylated N-glycans	997:1022	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	4	32	theme	amine-reactive	639:652	arg1	slide					654:658	an amine-reactive slide	636:658	an amine-reactive slide	636:658	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
32809822	3	33	theme	pooled	589:594	arg1	serum					596:600	a pooled serum standard	587:609	a pooled serum standard	587:609	A novel slide-based N-glycan profiling method was evaluated for sensitivity and reproducibility using a pooled serum standard.
32809822	5	34	theme	method	1063:1068	arg1	adaptability					1042:1053	the adaptability	1038:1053	the adaptability of this method for the determination of structural information	1038:1116	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	3	35	theme	profiling	514:522	arg1	method					524:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method was evaluated for sensitivity and reproducibility using a pooled serum standard.
32809822	6	36	theme	small	1148:1152	arg1	set					1167:1169	a small pooled serum set	1146:1169	a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion	1146:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	3	37	theme	N-glycan	505:512	arg1	method					524:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method was evaluated for sensitivity and reproducibility using a pooled serum standard.
32809822	6	38	dep	obese	1183:1187	arg1	patients					1201:1208	patients	1201:1208	patients	1201:1208	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	1	39	attach	released	156:163	arg2	N-glycans					146:154	N-glycans	146:154	N-glycans released from serum and plasma glycoproteins	146:199	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	39	attach	released	156:163	arg1	serum					170:174	serum	170:174	serum	170:174	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	39	attach	released	156:163	arg1	plasma					180:185	plasma	180:185	plasma	180:185	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	1	40	dep	serum	170:174	arg1	glycoproteins					187:199	glycoproteins	187:199	glycoproteins	187:199	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	4	41	theme	desalted	677:684	arg1	slide					654:658	an amine-reactive slide	636:658	an amine-reactive slide	636:658	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
32809822	5	42	theme	N-glycan	841:848	arg1	species					850:856	over 75 N-glycan species	833:856	over 75 N-glycan species	833:856	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	0	43	theme	Serum	28:32	arg1	Profiling					15:23	Rapid N-Glycan Profiling	0:23	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry	0:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	2	44	theme	diagnostic	466:475	arg1	potential					427:435	their potential	421:435	their potential for use	421:443	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	2	44	theme	diagnostic	466:475	arg1	assays					477:482	standard clinical diagnostic assays	448:482	standard clinical diagnostic assays	448:482	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	6	45	theme	breast	1219:1224	arg1	cancer					1226:1231	breast cancer	1219:1231	breast cancer	1219:1231	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	2	46	theme	clinical	457:464	arg1	potential					427:435	their potential	421:435	their potential for use	421:443	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	2	46	theme	clinical	457:464	arg1	assays					477:482	standard clinical diagnostic assays	448:482	standard clinical diagnostic assays	448:482	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	5	47	located	detected	865:872	arg1	h.					920:921	h.	920:921	h.	920:921	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	5	47	located	detected	865:872	arg2	species					850:856	over 75 N-glycan species	833:856	over 75 N-glycan species	833:856	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	7	48	theme	N-glycan	1346:1353	arg1	profiling					1355:1363	N-glycan profiling	1346:1363	N-glycan profiling of serum and plasma	1346:1383	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	5	49	theme	information	1106:1116	arg1	determination					1078:1090	the determination	1074:1090	the determination of structural information	1074:1116	Routinely, over 75 N-glycan species can be detected from one microliter of serum in less than 6.5 h. Additionally, endoglycosidase F3 was applied to this workflow to identify core-fucosylated N-glycans and displayed the adaptability of this method for the determination of structural information.
32809822	3	50	theme	novel	487:491	arg1	method					524:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method was evaluated for sensitivity and reproducibility using a pooled serum standard.
32809822	0	51	theme	Plasma	38:43	arg1	Profiling					15:23	Rapid N-Glycan Profiling	0:23	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry	0:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	3	52	theme	standard	602:609	arg1	serum					596:600	a pooled serum standard	587:609	a pooled serum standard	587:609	A novel slide-based N-glycan profiling method was evaluated for sensitivity and reproducibility using a pooled serum standard.
32809822	3	53	theme	slide-based	493:503	arg1	method					524:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method	485:529	A novel slide-based N-glycan profiling method was evaluated for sensitivity and reproducibility using a pooled serum standard.
32809822	7	54	theme	method	1335:1340	arg1	sensitivity					1294:1304	sensitivity	1294:1304	sensitivity	1294:1304	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	7	54	theme	method	1335:1340	arg1	adaptability					1311:1322	adaptability	1311:1322	adaptability	1311:1322	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	7	54	theme	method	1335:1340	arg1	reproducibility					1277:1291	reproducibility	1277:1291	reproducibility	1277:1291	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	7	55	theme	serum	1368:1372	arg1	profiling					1355:1363	N-glycan profiling	1346:1363	N-glycan profiling of serum and plasma	1346:1383	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	4	56	theme	peptide	724:730	arg1	F					746:746	peptide N-glycosidase F	724:746	peptide N-glycosidase F	724:746	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
32809822	7	57	theme	plasma	1378:1383	arg1	profiling					1355:1363	N-glycan profiling	1346:1363	N-glycan profiling of serum and plasma	1346:1383	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	6	58	theme	serum	1161:1165	arg1	set					1167:1169	a small pooled serum set	1146:1169	a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion	1146:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	0	59	theme	Novel	50:54	arg1	Spectrometry					81:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	a Novel Slide-Based Imaging Mass Spectrometry	48:92	Rapid N-Glycan Profiling of Serum and Plasma by a Novel Slide-Based Imaging Mass Spectrometry Workflow.
32809822	6	60	from	nonobese	1192:1199	arg1	set					1167:1169	a small pooled serum set	1146:1169	a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion	1146:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	4	61	theme	mass	803:806	arg1	spectrometry					808:819	mass spectrometry	803:819	mass spectrometry	803:819	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
32809822	6	62	contain	had	1215:1217	arg2	cancer					1226:1231	breast cancer	1219:1231	breast cancer	1219:1231	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	6	62	contain	had	1215:1217	arg1	set					1167:1169	a small pooled serum set	1146:1169	a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion	1146:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	6	62	contain	had	1215:1217	arg2	lesion					1245:1250	a benign lesion	1236:1250	a benign lesion	1236:1250	This method was applied to a small pooled serum set from either obese or nonobese patients that had breast cancer or a benign lesion.
32809822	4	63	theme	delipidated	661:671	arg1	slide					654:658	an amine-reactive slide	636:658	an amine-reactive slide	636:658	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
32809822	1	64	theme	many	223:226	arg1	diseases					228:235	many diseases	223:235	many diseases	223:235	Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts.
32809822	7	65	theme	novel	1329:1333	arg1	method					1335:1340	a novel method	1327:1340	a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics	1327:1433	This study confirms the reproducibility, sensitivity, and adaptability of a novel method for N-glycan profiling of serum and plasma for potential application to clinical diagnostics.
32809822	2	66	theme	processing	358:367	arg1	steps					369:373	multiple processing steps	349:373	multiple processing steps	349:373	Assays used for N-glycan profiling in these fluids currently require multiple processing steps and have limited throughput, thus diminishing their potential for use as standard clinical diagnostic assays.
32809822	4	67	dep	MALDI-FTICR	776:786	arg1	spectrometry					808:819	mass spectrometry	803:819	mass spectrometry	803:819	Serum was spotted on to an amine-reactive slide, delipidated and desalted with a series of washes, sprayed with peptide N-glycosidase F and matrix, and analyzed by MALDI-FTICR or MALDI-Q-TOF mass spectrometry.
34717971	7	0	theme	clinical	1246:1253	arg1	samples					1255:1261	clinical samples	1246:1261	clinical samples from infected individuals	1246:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	6	1	gly	glycosylation	1129:1141	arg1	HexaPro					1146:1152	HexaPro	1146:1152	HexaPro	1146:1152	However, there are site-specific differences in glycosylation of HexaPro when compared to 2P.
34717971	2	2	from	advances	398:405	arg1	engineering					418:428	protein engineering	410:428	protein engineering	410:428	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	2	3	theme	spike	346:350	arg1	glycoprotein					356:367	the trimeric spike (S) glycoprotein	333:367	the trimeric spike (S) glycoprotein	333:367	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	0	4	theme	Mimetic	90:96	arg1	SARS-CoV-2					67:76	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	8	5	theme	N-linked	1513:1520	arg1	glycans					1522:1528	all N-linked glycans	1509:1528	all N-linked glycans	1509:1528	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	7	6	from	individuals	1277:1287	arg1	reactivity					1232:1241	the serological reactivity	1216:1241	the serological reactivity of clinical samples from infected individuals	1216:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	7	6	from	individuals	1277:1287	arg1	samples					1255:1261	clinical samples	1246:1261	clinical samples from infected individuals	1246:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	1	7	theme	antigenic	170:178	arg1	surface					180:186	the antigenic surface	166:186	the antigenic surface of viruses	166:197	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	1	8	gly	glycosylation	109:121	arg1	glycoproteins					132:144	viral glycoproteins	126:144	viral glycoproteins	126:144	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	2	9	theme	trimeric	337:344	arg1	glycoprotein					356:367	the trimeric spike (S) glycoprotein	333:367	the trimeric spike (S) glycoprotein	333:367	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	4	10	theme	substitutions	786:798	arg1	influence					767:775	the influence	763:775	the influence of these substitutions on glycan processing	763:819	Although the substitutions greatly enhanced expression whilst not compromising protein structure, the influence of these substitutions on glycan processing has not been explored.
34717971	2	11	theme	low	299:301	arg1	yields					303:308	The low yields	295:308	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2	295:383	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	5	12	gly	glycosylation	890:902	arg1	HexaPro					931:937	the expression-enhanced HexaPro	907:937	the expression-enhanced HexaPro	907:937	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	5	13	theme	HexaPro	931:937	arg1	glycosylation					890:902	the site-specific N-linked glycosylation	863:902	the site-specific N-linked glycosylation of the expression-enhanced HexaPro	863:937	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	2	14	theme	soluble	317:323	arg1	form					325:328	the soluble form	313:328	the soluble form of the trimeric spike (S) glycoprotein	313:367	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	7	15	theme	2P	1321:1322	arg1	protein					1324:1330	2P protein	1321:1330	2P protein	1321:1330	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	6	16	theme	site-specific	1100:1112	arg1	differences					1114:1124	site-specific differences	1100:1124	site-specific differences in glycosylation of HexaPro	1100:1152	However, there are site-specific differences in glycosylation of HexaPro when compared to 2P.
34717971	2	17	gly	glycoprotein	489:500	arg1	glycoprotein					489:500	the glycoprotein	485:500	the glycoprotein	485:500	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	2	18	theme	glycoprotein	356:367	arg1	form					325:328	the soluble form	313:328	the soluble form of the trimeric spike (S) glycoprotein	313:367	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	1	19	theme	surface	180:186	arg1	glycosylation					109:121	Extensive glycosylation	99:121	Extensive glycosylation of viral glycoproteins	99:144	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	1	19	theme	surface	180:186	arg1	feature					155:161	a key feature	149:161	a key feature of the antigenic surface of viruses	149:197	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	2	20	theme	glycoprotein	489:500	arg1	yields					475:480	yields	475:480	yields	475:480	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	2	20	theme	glycoprotein	489:500	arg1	stability					461:469	stability	461:469	stability	461:469	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	8	21	theme	glycan	1472:1477	arg1	protein					1492:1498	glycan engineered S protein	1472:1498	glycan engineered S protein	1472:1498	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	5	22	theme	N-linked	881:888	arg1	glycosylation					890:902	the site-specific N-linked glycosylation	863:902	the site-specific N-linked glycosylation of the expression-enhanced HexaPro	863:937	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	8	23	from	changes	1636:1642	arg1	glycosylation					1647:1659	glycosylation	1647:1659	glycosylation	1647:1659	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	7	24	theme	samples	1255:1261	arg1	reactivity					1232:1241	the serological reactivity	1216:1241	the serological reactivity of clinical samples from infected individuals	1216:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	9	25	theme	glycan	1708:1713	arg1	processing					1715:1724	glycan processing	1708:1724	glycan processing	1708:1724	These observations suggest that variations in glycan processing will not impact the serological assessments currently being performed across the globe.
34717971	4	26	from	influence	767:775	arg1	processing					810:819	glycan processing	803:819	glycan processing	803:819	Although the substitutions greatly enhanced expression whilst not compromising protein structure, the influence of these substitutions on glycan processing has not been explored.
34717971	1	27	theme	Extensive	99:107	arg1	glycosylation					109:121	Extensive glycosylation	99:121	Extensive glycosylation of viral glycoproteins	99:144	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	1	27	theme	Extensive	99:107	arg1	feature					155:161	a key feature	149:161	a key feature of the antigenic surface of viruses	149:197	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	3	28	theme	expression-enhanced	514:532	arg1	version					534:540	The latest expression-enhanced version	503:540	The latest expression-enhanced version of the spike	503:553	The latest expression-enhanced version of the spike incorporates six proline substitutions to stabilize the prefusion conformation (termed SARS-CoV-2 S HexaPro).
34717971	1	29	theme	viruses	191:197	arg1	surface					180:186	the antigenic surface	166:186	the antigenic surface of viruses	166:197	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	1	30	theme	recombinant	271:281	arg1	production					283:292	their recombinant production	265:292	their recombinant production	265:292	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	2	31	gly	glycoprotein	356:367	arg1	glycoprotein					356:367	the trimeric spike (S) glycoprotein	333:367	the trimeric spike (S) glycoprotein	333:367	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	3	32	theme	proline	572:578	arg1	substitutions					580:592	six proline substitutions	568:592	six proline substitutions	568:592	The latest expression-enhanced version of the spike incorporates six proline substitutions to stabilize the prefusion conformation (termed SARS-CoV-2 S HexaPro).
34717971	7	33	theme	infected	1268:1275	arg1	individuals					1277:1287	infected individuals	1268:1287	infected individuals	1268:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	7	34	theme	IgG	1359:1361	arg1	responses					1377:1385	IgG, IgA, and IgM responses	1359:1385	IgG, IgA, and IgM responses	1359:1385	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	8	35	theme	large	1624:1628	arg1	changes					1636:1642	large scale changes	1624:1642	large scale changes in glycosylation	1624:1659	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	1	36	theme	production	283:292	arg1	manner					255:260	the manner	251:260	the manner of their recombinant production	251:292	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	5	37	theme	earlier	960:966	arg1	version					968:974	an earlier version	957:974	an earlier version containing two proline substitutions (2P)	957:1016	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	3	38	theme	spike	549:553	arg1	version					534:540	The latest expression-enhanced version	503:540	The latest expression-enhanced version of the spike	503:553	The latest expression-enhanced version of the spike incorporates six proline substitutions to stabilize the prefusion conformation (termed SARS-CoV-2 S HexaPro).
34717971	5	39	theme	proline	991:997	arg1	2P					1014:1015	2P	1014:1015	2P	1014:1015	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	5	39	theme	proline	991:997	arg1	substitutions					999:1011	two proline substitutions	987:1011	two proline substitutions (2P)	987:1016	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	0	40	theme	Serological	18:28	arg1	Reactivity					30:39	Serological Reactivity	18:39	Serological Reactivity	18:39	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	9	41	from	variations	1694:1703	arg1	processing					1715:1724	glycan processing	1708:1724	glycan processing	1708:1724	These observations suggest that variations in glycan processing will not impact the serological assessments currently being performed across the globe.
34717971	1	42	gly	glycoproteins	132:144	arg1	glycoproteins					132:144	viral glycoproteins	126:144	viral glycoproteins	126:144	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	1	43	theme	viral	126:130	arg1	glycoproteins					132:144	viral glycoproteins	126:144	viral glycoproteins	126:144	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	5	44	contain	containing	976:985	arg1	version					968:974	an earlier version	957:974	an earlier version containing two proline substitutions (2P)	957:1016	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	5	44	contain	containing	976:985	arg2	2P					1014:1015	2P	1014:1015	2P	1014:1015	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	5	44	contain	containing	976:985	arg2	substitutions					999:1011	two proline substitutions	987:1011	two proline substitutions (2P)	987:1016	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	1	45	theme	glycan	207:212	arg1	processing					214:223	glycan processing	207:223	glycan processing	207:223	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	8	46	theme	S	1490:1490	arg1	protein					1492:1498	glycan engineered S protein	1472:1498	glycan engineered S protein	1472:1498	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	0	47	gly	Glycosylation	0:12	arg1	SARS-CoV-2					67:76	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	5	48	theme	site-specific	867:879	arg1	glycosylation					890:902	the site-specific N-linked glycosylation	863:902	the site-specific N-linked glycosylation of the expression-enhanced HexaPro	863:937	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	7	49	from	reactivity	1232:1241	arg1	individuals					1277:1287	infected individuals	1268:1287	infected individuals	1268:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	3	50	theme	SARS-CoV-2	642:651	arg1	HexaPro					655:661	SARS-CoV-2 S HexaPro	642:661	SARS-CoV-2 S HexaPro	642:661	The latest expression-enhanced version of the spike incorporates six proline substitutions to stabilize the prefusion conformation (termed SARS-CoV-2 S HexaPro).
34717971	7	51	theme	serological	1220:1230	arg1	reactivity					1232:1241	the serological reactivity	1216:1241	the serological reactivity of clinical samples from infected individuals	1216:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	0	52	theme	SARS-CoV-2	67:76	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation	0:12	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	0	52	theme	SARS-CoV-2	67:76	arg1	Reactivity					30:39	Serological Reactivity	18:39	Serological Reactivity	18:39	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	7	53	theme	reactivity	1232:1241	arg1	analysis					1204:1211	analysis	1204:1211	analysis of the serological reactivity of clinical samples from infected individuals	1204:1287	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	9	54	theme	serological	1746:1756	arg1	assessments					1758:1768	the serological assessments	1742:1768	the serological assessments currently being performed across the globe	1742:1811	These observations suggest that variations in glycan processing will not impact the serological assessments currently being performed across the globe.
34717971	3	55	theme	S	653:653	arg1	HexaPro					655:661	SARS-CoV-2 S HexaPro	642:661	SARS-CoV-2 S HexaPro	642:661	The latest expression-enhanced version of the spike incorporates six proline substitutions to stabilize the prefusion conformation (termed SARS-CoV-2 S HexaPro).
34717971	1	56	theme	glycoproteins	132:144	arg1	glycosylation					109:121	Extensive glycosylation	99:121	Extensive glycosylation of viral glycoproteins	99:144	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	1	56	theme	glycoproteins	132:144	arg1	feature					155:161	a key feature	149:161	a key feature of the antigenic surface of viruses	149:197	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	0	57	theme	Expression-enhanced	47:65	arg1	SARS-CoV-2					67:76	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	8	58	theme	engineered	1479:1488	arg1	protein					1492:1498	glycan engineered S protein	1472:1498	glycan engineered S protein	1472:1498	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	8	59	link	N-linked	1513:1520	arg1	glycans					1522:1528	all N-linked glycans	1509:1528	all N-linked glycans	1509:1528	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	5	60	theme	viral	1060:1064	arg1	glycosylation					1066:1078	native viral glycosylation	1053:1078	native viral glycosylation	1053:1078	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	5	61	theme	native	1053:1058	arg1	glycosylation					1066:1078	native viral glycosylation	1053:1078	native viral glycosylation	1053:1078	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	2	62	from	SARS-CoV-2	374:383	arg1	yields					303:308	The low yields	295:308	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2	295:383	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	2	63	dep	stability	461:469	arg1	the					457:459	the	457:459	the	457:459	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	5	64	link	N-linked	881:888	arg1	glycosylation					890:902	the site-specific N-linked glycosylation	863:902	the site-specific N-linked glycosylation of the expression-enhanced HexaPro	863:937	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	5	65	theme	glycosylation	1066:1078	arg1	features					1041:1048	features	1041:1048	features of native viral glycosylation	1041:1078	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	7	66	theme	IgM	1373:1375	arg1	responses					1377:1385	IgG, IgA, and IgM responses	1359:1385	IgG, IgA, and IgM responses	1359:1385	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	2	67	theme	form	325:328	arg1	yields					303:308	The low yields	295:308	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2	295:383	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	6	68	theme	HexaPro	1146:1152	arg1	glycosylation					1129:1141	glycosylation	1129:1141	glycosylation of HexaPro	1129:1152	However, there are site-specific differences in glycosylation of HexaPro when compared to 2P.
34717971	4	69	theme	glycan	803:808	arg1	processing					810:819	glycan processing	803:819	glycan processing	803:819	Although the substitutions greatly enhanced expression whilst not compromising protein structure, the influence of these substitutions on glycan processing has not been explored.
34717971	8	70	theme	protein	1492:1498	arg1	analysis					1460:1467	an analysis	1457:1467	an analysis	1457:1467	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	1	71	theme	key	151:153	arg1	glycosylation					109:121	Extensive glycosylation	99:121	Extensive glycosylation of viral glycoproteins	99:144	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	1	71	theme	key	151:153	arg1	feature					155:161	a key feature	149:161	a key feature of the antigenic surface of viruses	149:197	Extensive glycosylation of viral glycoproteins is a key feature of the antigenic surface of viruses and yet glycan processing can also be influenced by the manner of their recombinant production.
34717971	4	72	theme	protein	744:750	arg1	structure					752:760	protein structure	744:760	protein structure	744:760	Although the substitutions greatly enhanced expression whilst not compromising protein structure, the influence of these substitutions on glycan processing has not been explored.
34717971	0	73	theme	Spike	84:88	arg1	SARS-CoV-2					67:76	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	5	74	theme	expression-enhanced	911:929	arg1	HexaPro					931:937	the expression-enhanced HexaPro	907:937	the expression-enhanced HexaPro	907:937	Here, we show that the site-specific N-linked glycosylation of the expression-enhanced HexaPro resembles that of an earlier version containing two proline substitutions (2P), and that both capture features of native viral glycosylation.
34717971	3	75	theme	prefusion	611:619	arg1	conformation					621:632	the prefusion conformation	607:632	the prefusion conformation (termed SARS-CoV-2 S HexaPro)	607:662	The latest expression-enhanced version of the spike incorporates six proline substitutions to stabilize the prefusion conformation (termed SARS-CoV-2 S HexaPro).
34717971	6	76	from	differences	1114:1124	arg1	glycosylation					1129:1141	glycosylation	1129:1141	glycosylation of HexaPro	1129:1152	However, there are site-specific differences in glycosylation of HexaPro when compared to 2P.
34717971	2	77	theme	S	353:353	arg1	glycoprotein					356:367	the trimeric spike (S) glycoprotein	333:367	the trimeric spike (S) glycoprotein	333:367	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	7	78	theme	IgA	1364:1366	arg1	responses					1377:1385	IgG, IgA, and IgM responses	1359:1385	IgG, IgA, and IgM responses	1359:1385	Despite these discrepancies, analysis of the serological reactivity of clinical samples from infected individuals confirmed that both HexaPro and 2P protein are equally able to detect IgG, IgA, and IgM responses in all sera analysed.
34717971	8	79	theme	scale	1630:1634	arg1	changes					1636:1642	large scale changes	1624:1642	large scale changes in glycosylation	1624:1659	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
34717971	0	80	theme	Viral	78:82	arg1	SARS-CoV-2					67:76	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic	44:96	Glycosylation and Serological Reactivity of an Expression-enhanced SARS-CoV-2 Viral Spike Mimetic.
34717971	2	81	theme	protein	410:416	arg1	engineering					418:428	protein engineering	410:428	protein engineering	410:428	The low yields of the soluble form of the trimeric spike (S) glycoprotein from SARS-CoV-2 has prompted advances in protein engineering that have greatly enhanced the stability and yields of the glycoprotein.
34717971	3	82	theme	latest	507:512	arg1	version					534:540	The latest expression-enhanced version	503:540	The latest expression-enhanced version of the spike	503:553	The latest expression-enhanced version of the spike incorporates six proline substitutions to stabilize the prefusion conformation (termed SARS-CoV-2 S HexaPro).
34717971	8	83	theme	serological	1584:1594	arg1	activity					1596:1603	serological activity	1584:1603	serological activity	1584:1603	Moreover, we extend this observation to include an analysis of glycan engineered S protein, whereby all N-linked glycans were converted to oligomannose-type and conclude that serological activity is not impacted by large scale changes in glycosylation.
33629527	2	0	theme	viral	349:353	arg1	proteins					355:362	immunogenic viral proteins	337:362	immunogenic viral proteins	337:362	In contrast, glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems, are hardly analyzed yet.
33629527	1	1	theme	blood	255:259	arg1	factors					270:276	blood clotting factors	255:276	blood clotting factors	255:276	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	3	2	dep	proteins	485:492	arg1	neuraminidase					517:529	neuraminidase	517:529	neuraminidase (NA)	517:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	2	dep	proteins	485:492	arg1	hemagglutinin					494:506	hemagglutinin	494:506	hemagglutinin (HA)	494:511	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	2	dep	proteins	485:492	arg1	proteins					485:492	The influenza A virus (IAV) proteins	457:492	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA)	457:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	2	dep	proteins	485:492	arg1	NA					532:533	NA	532:533	NA	532:533	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	2	dep	proteins	485:492	arg1	HA					509:510	HA	509:510	HA	509:510	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	10	3	theme	A	1668:1668	arg1	epitopes					1670:1677	blood group A epitopes	1656:1677	blood group A epitopes	1656:1677	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	10	4	link	alpha-linked	1591:1602	arg1	s					1614:1614	s	1614:1614	s	1614:1614	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	10	4	link	alpha-linked	1591:1602	arg1	galactose					1604:1612	alpha-linked galactose	1591:1612	alpha-linked galactose(s)	1591:1615	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	0	5	theme	Comprehensive	0:12	arg1	analysis					30:37	Comprehensive N-glycosylation analysis	0:37	Comprehensive N-glycosylation analysis of the influenza A virus	0:62	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	1	6	theme	quality	166:172	arg1	attribute					174:182	a critical quality attribute	155:182	a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies	155:302	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	1	6	theme	quality	166:172	arg1	Glycosylation					124:136	Glycosylation	124:136	Glycosylation	124:136	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	6	7	theme	MDCK	1122:1125	arg1	lines					1132:1136	both MDCK cell lines	1117:1136	both MDCK cell lines	1117:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	3	8	theme	multiple	541:548	arg1	sites					566:570	multiple N-glycosylation sites	541:570	multiple N-glycosylation sites	541:570	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	8	9	located	found	1362:1366	arg2	NA					1355:1356	NA	1355:1356	NA	1355:1356	In contrast, NA was found to be exclusively N-glycosylated at site N73.
33629527	8	9	located	found	1362:1366	arg1	contrast					1345:1352	contrast	1345:1352	contrast	1345:1352	In contrast, NA was found to be exclusively N-glycosylated at site N73.
33629527	11	10	theme	glycan	1725:1730	arg1	pattern					1732:1738	the overall glycan pattern	1713:1738	the overall glycan pattern	1713:1738	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	0	11	theme	MDCK	112:115	arg1	cells					117:121	adherent and suspension MDCK cells	88:121	adherent and suspension MDCK cells	88:121	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	10	12	theme	group	1662:1666	arg1	epitopes					1670:1677	blood group A epitopes	1656:1677	blood group A epitopes	1656:1677	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	9	13	theme	N-glycan	1425:1432	arg1	structures					1434:1443	Almost all N-glycan structures	1414:1443	Almost all N-glycan structures	1414:1443	Almost all N-glycan structures were fucosylated.
33629527	8	14	theme	site	1404:1407	arg1	N73					1409:1411	site N73	1404:1411	site N73	1404:1411	In contrast, NA was found to be exclusively N-glycosylated at site N73.
33629527	3	15	contain	have	634:637	arg2	effects					646:652	strong effects	639:652	strong effects	639:652	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	15	contain	have	634:637	arg1	alteration					577:586	alteration	577:586	alteration of N-glycan micro- and macroheterogeneity	577:628	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	11	16	theme	relative	1760:1767	arg1	abundance					1769:1777	the relative abundance	1756:1777	the relative abundance of individual structures	1756:1802	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	1	17	theme	recombinant	206:216	arg1	biopharmaceuticals					218:235	recombinant biopharmaceuticals	206:235	recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies	206:302	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	1	17	theme	recombinant	206:216	arg1	hormones					245:252	hormones	245:252	hormones	245:252	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	1	17	theme	recombinant	206:216	arg1	antibodies					293:302	monoclonal antibodies	282:302	monoclonal antibodies	282:302	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	1	17	theme	recombinant	206:216	arg1	factors					270:276	blood clotting factors	255:276	blood clotting factors	255:276	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	12	18	theme	complex-type	1914:1925	arg1	N-glycans					1927:1935	multiantennary complex-type N-glycans	1899:1935	multiantennary complex-type N-glycans	1899:1935	This concerned, in particular, oligomannose-type, alpha-linked galactose, and multiantennary complex-type N-glycans.
33629527	5	19	theme	suspension	1018:1027	arg1	line					1034:1037	its corresponding suspension cell line	1000:1037	its corresponding suspension cell line	1000:1037	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	19	theme	suspension	1018:1027	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	20	theme	related	909:915	arg1	MDCK					944:947	MDCK	944:947	MDCK	944:947	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	20	theme	related	909:915	arg1	kidney					936:941	two closely related Madin-Darby canine kidney	897:941	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	3	21	theme	micro-	600:605	arg1	alteration					577:586	alteration	577:586	alteration of N-glycan micro- and macroheterogeneity	577:628	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	5	22	theme	canine	929:934	arg1	MDCK					944:947	MDCK	944:947	MDCK	944:947	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	22	theme	canine	929:934	arg1	kidney					936:941	two closely related Madin-Darby canine kidney	897:941	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	10	23	theme	H	1643:1643	arg1	type					1645:1648	blood group H type 2	1631:1650	blood group H type 2	1631:1650	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	7	24	theme	microheterogeneity	1189:1206	arg1	analysis					1161:1168	Detailed analysis	1152:1168	Detailed analysis of the HA N-glycan microheterogeneity	1152:1206	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	9	25	gly	fucosylated	1450:1460	arg1	structures					1434:1443	Almost all N-glycan structures	1414:1443	Almost all N-glycan structures	1414:1443	Almost all N-glycan structures were fucosylated.
33629527	7	26	theme	HA	1177:1178	arg1	microheterogeneity					1189:1206	the HA N-glycan microheterogeneity	1173:1206	the HA N-glycan microheterogeneity	1173:1206	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	12	27	theme	alpha-linked	1871:1882	arg1	galactose					1884:1892	alpha-linked galactose	1871:1892	alpha-linked galactose	1871:1892	This concerned, in particular, oligomannose-type, alpha-linked galactose, and multiantennary complex-type N-glycans.
33629527	10	28	theme	group	1637:1641	arg1	type					1645:1648	blood group H type 2	1631:1650	blood group H type 2	1631:1650	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	7	29	theme	Detailed	1152:1159	arg1	analysis					1161:1168	Detailed analysis	1152:1168	Detailed analysis of the HA N-glycan microheterogeneity	1152:1206	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	7	30	theme	head	1313:1316	arg1	region					1318:1323	the head region	1309:1323	the head region of the molecule	1309:1339	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	4	31	gly	glycoproteins	815:827	arg1	glycoproteins					815:827	IAV glycoproteins	811:827	IAV glycoproteins	811:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	8	32	gly	N-glycosylated	1386:1399	arg1	NA					1355:1356	NA	1355:1356	NA	1355:1356	In contrast, NA was found to be exclusively N-glycosylated at site N73.
33629527	8	32	gly	N-glycosylated	1386:1399	arg2	N73					1409:1411	site N73	1404:1411	site N73	1404:1411	In contrast, NA was found to be exclusively N-glycosylated at site N73.
33629527	4	33	theme	glycoanalytical	729:743	arg1	workflow					745:752	a versatile and powerful glycoanalytical workflow	704:752	a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins	704:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	3	34	theme	influenza	461:469	arg1	IAV					480:482	IAV	480:482	IAV	480:482	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	34	theme	influenza	461:469	arg1	virus					473:477	The influenza A virus	457:477	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA)	457:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	1	35	theme	monoclonal	282:291	arg1	antibodies					293:302	monoclonal antibodies	282:302	monoclonal antibodies	282:302	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	7	36	theme	located	1291:1297	arg1	sites					1285:1289	N-glycosylation sites	1269:1289	N-glycosylation sites located closer to the head region of the molecule	1269:1339	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	3	37	contain	have	536:539	arg1	neuraminidase					517:529	neuraminidase	517:529	neuraminidase (NA)	517:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	37	contain	have	536:539	arg1	hemagglutinin					494:506	hemagglutinin	494:506	hemagglutinin (HA)	494:511	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	37	contain	have	536:539	arg2	sites					566:570	multiple N-glycosylation sites	541:570	multiple N-glycosylation sites	541:570	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	37	contain	have	536:539	arg1	proteins					485:492	The influenza A virus (IAV) proteins	457:492	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA)	457:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	2	38	theme	expression	412:421	arg1	systems					423:429	the various expression systems	400:429	the various expression systems	400:429	In contrast, glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems, are hardly analyzed yet.
33629527	4	39	theme	glycoproteins	815:827	arg1	analysis					799:806	a comprehensive N-glycosylation analysis	767:806	a comprehensive N-glycosylation analysis of IAV glycoproteins	767:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	10	40	theme	blood	1631:1635	arg1	type					1645:1648	blood group H type 2	1631:1650	blood group H type 2	1631:1650	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	4	41	gly	N-glycosylation	783:797	arg1	glycoproteins					815:827	IAV glycoproteins	811:827	IAV glycoproteins	811:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	0	42	gly	N-glycosylation	14:28	arg1	virus					58:62	the influenza A virus	42:62	the influenza A virus	42:62	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	7	43	theme	N-glycosylation	1269:1283	arg1	sites					1285:1289	N-glycosylation sites	1269:1289	N-glycosylation sites located closer to the head region of the molecule	1269:1339	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	10	44	theme	N-glycan	1486:1493	arg1	structures					1495:1504	NA N-glycan structures	1483:1504	NA N-glycan structures	1483:1504	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	3	45	theme	macroheterogeneity	611:628	arg1	alteration					577:586	alteration	577:586	alteration of N-glycan micro- and macroheterogeneity	577:628	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	2	46	theme	immunogenic	337:347	arg1	proteins					355:362	immunogenic viral proteins	337:362	immunogenic viral proteins	337:362	In contrast, glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems, are hardly analyzed yet.
33629527	0	47	theme	A	56:56	arg1	virus					58:62	the influenza A virus	42:62	the influenza A virus	42:62	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	5	48	theme	corresponding	1004:1016	arg1	line					1034:1037	its corresponding suspension cell line	1000:1037	its corresponding suspension cell line	1000:1037	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	48	theme	corresponding	1004:1016	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	6	49	theme	virus	1089:1093	arg1	particles					1095:1103	virus particles	1089:1103	virus particles produced in both MDCK cell lines	1089:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	4	50	theme	N-glycosylation	783:797	arg1	analysis					799:806	a comprehensive N-glycosylation analysis	767:806	a comprehensive N-glycosylation analysis of IAV glycoproteins	767:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	3	51	theme	virus	473:477	arg1	neuraminidase					517:529	neuraminidase	517:529	neuraminidase (NA)	517:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	51	theme	virus	473:477	arg1	hemagglutinin					494:506	hemagglutinin	494:506	hemagglutinin (HA)	494:511	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	51	theme	virus	473:477	arg1	proteins					485:492	The influenza A virus (IAV) proteins	457:492	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA)	457:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	1	52	theme	biopharmaceuticals	218:235	arg1	production					192:201	the production	188:201	the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies	188:302	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	5	53	theme	adherent	972:979	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	53	theme	adherent	972:979	arg1	line					991:994	an adherent MDCK cell line	969:994	an adherent MDCK cell line	969:994	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	6	54	theme	NA	1081:1082	arg1	patterns					1062:1069	N-glycan patterns	1053:1069	N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines	1053:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	10	55	theme	hybrid-	1523:1529	arg1	structures					1548:1557	hybrid- and complex-type structures	1523:1557	hybrid- and complex-type structures	1523:1557	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	6	56	from	patterns	1062:1069	arg1	particles					1095:1103	virus particles	1089:1103	virus particles produced in both MDCK cell lines	1089:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	7	57	dep	located	1291:1297	arg1	closer					1299:1304	closer	1299:1304	closer	1299:1304	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	6	58	theme	HA	1074:1075	arg1	patterns					1062:1069	N-glycan patterns	1053:1069	N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines	1053:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	2	59	theme	proteins	355:362	arg1	patterns					325:332	glycan patterns	318:332	glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems,	318:430	In contrast, glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems, are hardly analyzed yet.
33629527	1	60	theme	clotting	261:268	arg1	factors					270:276	blood clotting factors	255:276	blood clotting factors	255:276	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	10	61	theme	complex-type	1535:1546	arg1	structures					1548:1557	hybrid- and complex-type structures	1523:1557	hybrid- and complex-type structures	1523:1557	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	10	62	theme	blood	1656:1660	arg1	epitopes					1670:1677	blood group A epitopes	1656:1677	blood group A epitopes	1656:1677	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	12	63	link	alpha-linked	1871:1882	arg1	galactose					1884:1892	alpha-linked galactose	1871:1892	alpha-linked galactose	1871:1892	This concerned, in particular, oligomannose-type, alpha-linked galactose, and multiantennary complex-type N-glycans.
33629527	1	64	theme	critical	157:164	arg1	attribute					174:182	a critical quality attribute	155:182	a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies	155:302	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	1	64	theme	critical	157:164	arg1	Glycosylation					124:136	Glycosylation	124:136	Glycosylation	124:136	Glycosylation is considered as a critical quality attribute for the production of recombinant biopharmaceuticals such as hormones, blood clotting factors, or monoclonal antibodies.
33629527	6	65	theme	cell	1127:1130	arg1	lines					1132:1136	both MDCK cell lines	1117:1136	both MDCK cell lines	1117:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	5	66	theme	A/PR/8/34	867:875	arg1	IAV					862:864	IAV	862:864	IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line	862:1037	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	66	theme	A/PR/8/34	867:875	arg1	H1N1					877:880	A/PR/8/34 H1N1	867:880	A/PR/8/34 H1N1	867:880	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	11	67	from	differences	1741:1751	arg1	abundance					1769:1777	the relative abundance	1756:1777	the relative abundance of individual structures	1756:1802	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	9	68	theme	all	1421:1423	arg1	structures					1434:1443	Almost all N-glycan structures	1414:1443	Almost all N-glycan structures	1414:1443	Almost all N-glycan structures were fucosylated.
33629527	11	69	theme	pattern	1732:1738	arg1	similarity					1699:1708	the similarity	1695:1708	the similarity of the overall glycan pattern	1695:1738	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	11	70	theme	structures	1793:1802	arg1	abundance					1769:1777	the relative abundance	1756:1777	the relative abundance of individual structures	1756:1802	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	3	71	gly	N-glycosylation	550:564	arg2	sites					566:570	multiple N-glycosylation sites	541:570	multiple N-glycosylation sites	541:570	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	10	72	theme	alpha-linked	1591:1602	arg1	s					1614:1614	s	1614:1614	s	1614:1614	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	10	72	theme	alpha-linked	1591:1602	arg1	galactose					1604:1612	alpha-linked galactose	1591:1612	alpha-linked galactose(s)	1591:1615	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	3	73	theme	N-glycosylation	550:564	arg1	sites					566:570	multiple N-glycosylation sites	541:570	multiple N-glycosylation sites	541:570	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	12	74	theme	multiantennary	1899:1912	arg1	N-glycans					1927:1935	multiantennary complex-type N-glycans	1899:1935	multiantennary complex-type N-glycans	1899:1935	This concerned, in particular, oligomannose-type, alpha-linked galactose, and multiantennary complex-type N-glycans.
33629527	5	75	theme	cell	1029:1032	arg1	line					1034:1037	its corresponding suspension cell line	1000:1037	its corresponding suspension cell line	1000:1037	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	75	theme	cell	1029:1032	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	3	76	theme	N-glycan	591:598	arg1	micro-					600:605	N-glycan micro-	591:605	N-glycan micro-	591:605	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	5	77	theme	Madin-Darby	917:927	arg1	MDCK					944:947	MDCK	944:947	MDCK	944:947	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	77	theme	Madin-Darby	917:927	arg1	kidney					936:941	two closely related Madin-Darby canine kidney	897:941	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	7	78	theme	molecule	1332:1339	arg1	region					1318:1323	the head region	1309:1323	the head region of the molecule	1309:1339	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	7	79	theme	N-glycan	1180:1187	arg1	microheterogeneity					1189:1206	the HA N-glycan microheterogeneity	1173:1206	the HA N-glycan microheterogeneity	1173:1206	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	8	80	from	N73	1409:1411	arg1	N-glycosylated					1386:1399	N-glycosylated	1386:1399	N-glycosylated	1386:1399	In contrast, NA was found to be exclusively N-glycosylated at site N73.
33629527	11	81	theme	overall	1717:1723	arg1	pattern					1732:1738	the overall glycan pattern	1713:1738	the overall glycan pattern	1713:1738	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	0	82	theme	adherent	88:95	arg1	cells					117:121	adherent and suspension MDCK cells	88:121	adherent and suspension MDCK cells	88:121	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	7	83	gly	N-glycosylation	1269:1283	arg2	sites					1285:1289	N-glycosylation sites	1269:1289	N-glycosylation sites located closer to the head region of the molecule	1269:1339	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	5	84	theme	cell	950:953	arg1	line					1034:1037	its corresponding suspension cell line	1000:1037	its corresponding suspension cell line	1000:1037	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	84	theme	cell	950:953	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	84	theme	cell	950:953	arg1	line					991:994	an adherent MDCK cell line	969:994	an adherent MDCK cell line	969:994	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	11	85	theme	individual	1782:1791	arg1	structures					1793:1802	individual structures	1782:1802	individual structures	1782:1802	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	0	86	theme	suspension	101:110	arg1	cells					117:121	adherent and suspension MDCK cells	88:121	adherent and suspension MDCK cells	88:121	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	6	87	theme	N-glycan	1053:1060	arg1	patterns					1062:1069	N-glycan patterns	1053:1069	N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines	1053:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	0	88	theme	N-glycosylation	14:28	arg1	analysis					30:37	Comprehensive N-glycosylation analysis	0:37	Comprehensive N-glycosylation analysis of the influenza A virus	0:62	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	5	89	theme	kidney	936:941	arg1	line					1034:1037	its corresponding suspension cell line	1000:1037	its corresponding suspension cell line	1000:1037	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	89	theme	kidney	936:941	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	89	theme	kidney	936:941	arg1	line					991:994	an adherent MDCK cell line	969:994	an adherent MDCK cell line	969:994	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	4	90	theme	versatile	706:714	arg1	workflow					745:752	a versatile and powerful glycoanalytical workflow	704:752	a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins	704:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	4	91	theme	powerful	720:727	arg1	workflow					745:752	a versatile and powerful glycoanalytical workflow	704:752	a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins	704:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	3	92	theme	A	471:471	arg1	IAV					480:482	IAV	480:482	IAV	480:482	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	3	92	theme	A	471:471	arg1	virus					473:477	The influenza A virus	457:477	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA)	457:534	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	0	93	theme	influenza	46:54	arg1	virus					58:62	the influenza A virus	42:62	the influenza A virus	42:62	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	4	94	theme	IAV	811:813	arg1	glycoproteins					815:827	IAV glycoproteins	811:827	IAV glycoproteins	811:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	2	95	theme	various	404:410	arg1	systems					423:429	the various expression systems	400:429	the various expression systems	400:429	In contrast, glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems, are hardly analyzed yet.
33629527	0	96	theme	virus	58:62	arg1	analysis					30:37	Comprehensive N-glycosylation analysis	0:37	Comprehensive N-glycosylation analysis of the influenza A virus	0:62	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
33629527	7	97	theme	higher	1247:1252	arg1	complexity					1254:1263	a higher complexity	1245:1263	a higher complexity for N-glycosylation sites located closer to the head region of the molecule	1245:1339	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	11	98	dep	similarity	1699:1708	arg1	contrast					1683:1690	contrast	1683:1690	contrast	1683:1690	In contrast to the similarity of the overall glycan pattern, differences in the relative abundance of individual structures were identified.
33629527	10	99	theme	NA	1483:1484	arg1	structures					1495:1504	NA N-glycan structures	1483:1504	NA N-glycan structures	1483:1504	Furthermore, HA and NA N-glycan structures were exclusively hybrid- and complex-type structures, to some extent terminated with alpha-linked galactose(s) but also with blood group H type 2 and blood group A epitopes.
33629527	6	100	from	particles	1095:1103	arg1	HA					1074:1075	HA	1074:1075	HA	1074:1075	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	6	100	from	particles	1095:1103	arg1	patterns					1062:1069	N-glycan patterns	1053:1069	N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines	1053:1136	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	6	100	from	particles	1095:1103	arg1	NA					1081:1082	NA	1081:1082	NA	1081:1082	As expected, N-glycan patterns of HA and NA from virus particles produced in both MDCK cell lines were similar.
33629527	5	101	theme	cell	986:989	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	101	theme	cell	986:989	arg1	line					991:994	an adherent MDCK cell line	969:994	an adherent MDCK cell line	969:994	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	3	102	theme	strong	639:644	arg1	effects					646:652	strong effects	639:652	strong effects	639:652	The influenza A virus (IAV) proteins hemagglutinin (HA) and neuraminidase (NA) have multiple N-glycosylation sites, and alteration of N-glycan micro- and macroheterogeneity can have strong effects on virulence and immunogenicity.
33629527	4	103	theme	comprehensive	769:781	arg1	analysis					799:806	a comprehensive N-glycosylation analysis	767:806	a comprehensive N-glycosylation analysis of IAV glycoproteins	767:827	Here, we present a versatile and powerful glycoanalytical workflow that enables a comprehensive N-glycosylation analysis of IAV glycoproteins.
33629527	2	104	theme	glycan	318:323	arg1	patterns					325:332	glycan patterns	318:332	glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems,	318:430	In contrast, glycan patterns of immunogenic viral proteins, which differ significantly between the various expression systems, are hardly analyzed yet.
33629527	5	105	theme	MDCK	981:984	arg1	lines					955:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	two closely related Madin-Darby canine kidney (MDCK) cell lines	897:959	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	5	105	theme	MDCK	981:984	arg1	line					991:994	an adherent MDCK cell line	969:994	an adherent MDCK cell line	969:994	We challenged our workflow with IAV (A/PR/8/34 H1N1) propagated in two closely related Madin-Darby canine kidney (MDCK) cell lines, namely an adherent MDCK cell line and its corresponding suspension cell line.
33629527	7	106	theme	increasing	1218:1227	arg1	variability					1229:1239	an increasing variability	1215:1239	an increasing variability	1215:1239	Detailed analysis of the HA N-glycan microheterogeneity showed an increasing variability and a higher complexity for N-glycosylation sites located closer to the head region of the molecule.
33629527	0	107	from	cells	117:121	arg1	proteins					64:71	proteins	64:71	proteins	64:71	Comprehensive N-glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells.
34101390	3	0	theme	capabilities	742:753	arg1	representative					713:726	representative	713:726	representative	713:726	Living cells metabolically convert these precursors to all types of O-GalNAc glycans representative of the cells' capabilities.
34101390	9	1	theme	Basic	1098:1102	arg1	Protocol					1104:1111	Basic Protocol 1	1098:1113	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	1	2	theme	current	366:372	arg1	methods					385:391	current analytical methods	366:391	current analytical methods	366:391	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	9	3	theme	Basic	1335:1339	arg1	Protocol					1341:1348	Basic Protocol 3	1335:1350	Basic Protocol 3	1335:1350	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	8	4	theme	Government	1042:1051	arg1	work					1053:1056	a U.S. Government work	1035:1056	a U.S. Government work	1035:1056	This article is a U.S. Government work and is in the public domain in the USA.
34101390	8	4	theme	Government	1042:1051	arg1	article					1024:1030	This article	1019:1030	This article	1019:1030	This article is a U.S. Government work and is in the public domain in the USA.
34101390	9	5	from	Preparation	1235:1245	arg1	cells					1281:1285	living cells	1274:1285	living cells	1274:1285	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	1	6	theme	O-glycan	274:281	arg1	diversity					294:302	O-glycan structural diversity	274:302	O-glycan structural diversity	274:302	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	0	7	theme	Mucin-Type	92:101	arg1	O-Glycans					103:111	Study Mucin-Type O-Glycans	86:111	Study Mucin-Type O-Glycans of Living Cells	86:127	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	1	8	theme	analytical	374:383	arg1	methods					385:391	current analytical methods	366:391	current analytical methods	366:391	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	8	9	theme	U.S.	1037:1040	arg1	work					1053:1056	a U.S. Government work	1035:1056	a U.S. Government work	1035:1056	This article is a U.S. Government work and is in the public domain in the USA.
34101390	8	9	theme	U.S.	1037:1040	arg1	article					1024:1030	This article	1019:1030	This article	1019:1030	This article is a U.S. Government work and is in the public domain in the USA.
34101390	1	10	theme	structural	283:292	arg1	diversity					294:302	O-glycan structural diversity	274:302	O-glycan structural diversity	274:302	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	0	11	theme	Study	86:90	arg1	O-Glycans					103:111	Study Mucin-Type O-Glycans	86:111	Study Mucin-Type O-Glycans of Living Cells	86:127	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	1	12	theme	methods	385:391	arg1	inadequacy					352:361	the inadequacy	348:361	the inadequacy of current analytical methods	348:391	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	2	13	theme	O-glycosylation	611:625	arg1	surrogates					589:598	surrogates	589:598	surrogates of protein O-glycosylation	589:625	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	13	theme	O-glycosylation	611:625	arg1	precursors					504:513	O-glycan precursors	495:513	O-glycan precursors	495:513	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	1	14	gly	glycoproteins	256:268	arg1	glycoproteins					256:268	glycoproteins	256:268	glycoproteins	256:268	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	4	15	theme	products	805:812	arg1	secretion					778:786	secretion	778:786	secretion	778:786	The amplification and secretion of the O-glycome products greatly facilitates their analysis and functional studies.
34101390	4	15	theme	products	805:812	arg1	amplification					760:772	amplification	760:772	amplification	760:772	The amplification and secretion of the O-glycome products greatly facilitates their analysis and functional studies.
34101390	9	16	theme	O-glycans	1377:1385	arg1	Conjugation					1353:1363	Conjugation	1353:1363	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	17	theme	cellular	1250:1257	arg1	O-glycans					1259:1267	cellular O-glycans	1250:1267	cellular O-glycans from living cells	1250:1285	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	18	theme	Cellular	1116:1123	arg1	reporter/amplification					1135:1156	Cellular O-glycome reporter/amplification	1116:1156	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	5	19	theme	preparative	919:929	arg1	applications					931:942	analytical and preparative applications	904:942	analytical and preparative applications	904:942	Here we describe protocols for analytical and preparative applications.
34101390	9	20	theme	individual	1497:1506	arg1	PYAB-Bn-O-glycan					1508:1523	individual PYAB-Bn-O-glycan	1497:1523	individual PYAB-Bn-O-glycan	1497:1523	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	21	theme	O-glycans	1259:1267	arg1	Preparation					1235:1245	Preparation	1235:1245	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	22	theme	O-glycome	1125:1133	arg1	reporter/amplification					1135:1156	Cellular O-glycome reporter/amplification	1116:1156	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	2	23	theme	new	418:420	arg1	tool					422:425	a new tool	416:425	a new tool	416:425	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	0	24	theme	O-Glycome	9:17	arg1	Reporter/Amplification					19:40	Cellular O-Glycome Reporter/Amplification	0:40	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.	0:128	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	0	24	theme	O-Glycome	9:17	arg1	CORA					43:46	CORA	43:46	CORA	43:46	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	9	25	theme	Basic	1423:1427	arg1	Protocol					1429:1436	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	26	theme	cellular	1368:1375	arg1	O-glycans					1377:1385	cellular O-glycans	1368:1385	cellular O-glycans	1368:1385	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	27	from	cells	1211:1215	arg1	analysis					1166:1173	the analysis	1162:1173	the analysis of mucin-type O-glycans from living cells	1162:1215	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	27	from	cells	1211:1215	arg1	O-glycans					1189:1197	mucin-type O-glycans	1178:1197	mucin-type O-glycans from living cells	1178:1215	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	0	28	theme	Cellular	0:7	arg1	Reporter/Amplification					19:40	Cellular O-Glycome Reporter/Amplification	0:40	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.	0:128	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	0	28	theme	Cellular	0:7	arg1	CORA					43:46	CORA	43:46	CORA	43:46	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	9	29	theme	bifunctional	1394:1405	arg1	tag					1419:1421	a bifunctional fluorescent tag	1392:1421	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	7	30	theme	Wiley	996:1000	arg1	LLC					1014:1016	Wiley Periodicals LLC	996:1016	Wiley Periodicals LLC	996:1016	Current Protocols published by Wiley Periodicals LLC.
34101390	4	31	dep	amplification	760:772	arg1	The					756:758	The	756:758	The	756:758	The amplification and secretion of the O-glycome products greatly facilitates their analysis and functional studies.
34101390	9	32	theme	functional	1291:1300	arg1	glycomics					1302:1310	functional glycomics	1291:1310	functional glycomics	1291:1310	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	8	33	theme	public	1072:1077	arg1	domain					1079:1084	the public domain	1068:1084	the public domain in the USA	1068:1095	This article is a U.S. Government work and is in the public domain in the USA.
34101390	0	34	theme	Cells	123:127	arg1	O-Glycans					103:111	Study Mucin-Type O-Glycans	86:111	Study Mucin-Type O-Glycans of Living Cells	86:127	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	7	35	theme	Periodicals	1002:1012	arg1	LLC					1014:1016	Wiley Periodicals LLC	996:1016	Wiley Periodicals LLC	996:1016	Current Protocols published by Wiley Periodicals LLC.
34101390	1	36	dep	O-glycosylation	141:155	arg1	O-glycome					169:177	O-glycome	169:177	O-glycome	169:177	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	1	36	dep	O-glycosylation	141:155	arg1	O-glycans					158:166	O-glycans	158:166	O-glycans	158:166	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	9	37	from	analysis	1166:1173	arg1	cells					1211:1215	living cells	1204:1215	living cells	1204:1215	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	38	theme	living	1274:1279	arg1	cells					1281:1285	living cells	1274:1285	living cells	1274:1285	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	39	theme	tag	1419:1421	arg1	Protocol					1429:1436	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	0	40	theme	Living	116:121	arg1	Cells					123:127	Living Cells	116:127	Living Cells	116:127	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	6	41	theme	©	945:945	arg1	2021					947:950	© 2021	945:950	© 2021	945:950	© 2021 The Authors.
34101390	2	42	theme	O-glycome	443:451	arg1	CORA					477:480	CORA	477:480	CORA	477:480	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	42	theme	O-glycome	443:451	arg1	reporter/amplification					453:474	cellular O-glycome reporter/amplification	434:474	cellular O-glycome reporter/amplification (CORA)	434:481	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	8	43	from	domain	1079:1084	arg1	USA					1093:1095	the USA	1089:1095	the USA	1089:1095	This article is a U.S. Government work and is in the public domain in the USA.
34101390	5	44	theme	analytical	904:913	arg1	applications					931:942	analytical and preparative applications	904:942	analytical and preparative applications	904:942	Here we describe protocols for analytical and preparative applications.
34101390	3	45	theme	Living	628:633	arg1	cells					635:639	Living cells	628:639	Living cells	628:639	Living cells metabolically convert these precursors to all types of O-GalNAc glycans representative of the cells' capabilities.
34101390	2	46	theme	cellular	434:441	arg1	CORA					477:480	CORA	477:480	CORA	477:480	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	46	theme	cellular	434:441	arg1	reporter/amplification					453:474	cellular O-glycome reporter/amplification	434:474	cellular O-glycome reporter/amplification (CORA)	434:481	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	47	theme	O-glycan	495:502	arg1	surrogates					589:598	surrogates	589:598	surrogates of protein O-glycosylation	589:625	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	47	theme	O-glycan	495:502	arg1	azido-Bn-α-GalNAc					549:565	azido-Bn-α-GalNAc	549:565	azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc)	549:583	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	47	theme	O-glycan	495:502	arg1	benzyl-α-GalNAc					516:530	benzyl-α-GalNAc	516:530	benzyl-α-GalNAc (Bn-α-GalNAc)	516:544	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	47	theme	O-glycan	495:502	arg1	precursors					504:513	O-glycan precursors	495:513	O-glycan precursors	495:513	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	48	theme	N3	568:569	arg1	azido-Bn-α-GalNAc					549:565	azido-Bn-α-GalNAc	549:565	azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc)	549:583	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	2	48	theme	N3	568:569	arg1	-Bn-α-GalNAc					571:582	N3 -Bn-α-GalNAc	568:582	N3 -Bn-α-GalNAc	568:582	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	9	49	theme	mucin-type	1178:1187	arg1	O-glycans					1189:1197	mucin-type O-glycans	1178:1197	mucin-type O-glycans from living cells	1178:1215	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	1	50	theme	important	211:219	arg1	modification					240:251	the most biologically important post-translational modification	189:251	the most biologically important post-translational modification in glycoproteins	189:268	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	0	51	theme	Analytical	50:59	arg1	Tools					77:81	Analytical and Preparative Tools	50:81	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.	0:128	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	2	52	theme	protein	603:609	arg1	O-glycosylation					611:625	protein O-glycosylation	603:625	protein O-glycosylation	603:625	We recently developed a new tool termed cellular O-glycome reporter/amplification (CORA), which uses O-glycan precursors, benzyl-α-GalNAc (Bn-α-GalNAc) or azido-Bn-α-GalNAc (N3 -Bn-α-GalNAc), as surrogates of protein O-glycosylation.
34101390	9	53	theme	fluorescent	1407:1417	arg1	tag					1419:1421	a bifunctional fluorescent tag	1392:1421	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	54	theme	O-glycans	1189:1197	arg1	analysis					1166:1173	the analysis	1162:1173	the analysis of mucin-type O-glycans from living cells	1162:1215	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	55	theme	glycan	1316:1321	arg1	microarrays					1323:1333	glycan microarrays	1316:1333	glycan microarrays	1316:1333	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	3	56	theme	representative	713:726	arg1	glycans					705:711	O-GalNAc glycans	696:711	O-GalNAc glycans representative of the cells' capabilities	696:753	Living cells metabolically convert these precursors to all types of O-GalNAc glycans representative of the cells' capabilities.
34101390	8	57	from	work	1053:1056	arg1	USA					1093:1095	the USA	1089:1095	the USA	1089:1095	This article is a U.S. Government work and is in the public domain in the USA.
34101390	9	58	theme	2D-HPLC	1441:1447	arg1	purification					1449:1460	2D-HPLC purification	1441:1460	2D-HPLC purification	1441:1460	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	59	dep	Protocol	1104:1111	arg1	Conjugation					1353:1363	Conjugation	1353:1363	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	59	dep	Protocol	1104:1111	arg1	purification					1449:1460	2D-HPLC purification	1441:1460	2D-HPLC purification	1441:1460	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	59	dep	Protocol	1104:1111	arg1	reporter/amplification					1135:1156	Cellular O-glycome reporter/amplification	1116:1156	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	59	dep	Protocol	1104:1111	arg1	identification					1479:1492	MALDI-TOF/MS identification	1466:1492	MALDI-TOF/MS identification	1466:1492	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	59	dep	Protocol	1104:1111	arg1	Preparation					1235:1245	Preparation	1235:1245	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	60	theme	living	1204:1209	arg1	cells					1211:1215	living cells	1204:1215	living cells	1204:1215	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	4	61	theme	O-glycome	795:803	arg1	products					805:812	the O-glycome products	791:812	the O-glycome products	791:812	The amplification and secretion of the O-glycome products greatly facilitates their analysis and functional studies.
34101390	1	62	theme	post-translational	221:238	arg1	modification					240:251	the most biologically important post-translational modification	189:251	the most biologically important post-translational modification in glycoproteins	189:268	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	1	63	from	modification	240:251	arg1	glycoproteins					256:268	glycoproteins	256:268	glycoproteins	256:268	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	3	64	theme	O-GalNAc	696:703	arg1	glycans					705:711	O-GalNAc glycans	696:711	O-GalNAc glycans representative of the cells' capabilities	696:753	Living cells metabolically convert these precursors to all types of O-GalNAc glycans representative of the cells' capabilities.
34101390	0	65	dep	Reporter/Amplification	19:40	arg1	Tools					77:81	Analytical and Preparative Tools	50:81	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.	0:128	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	1	66	theme	Mucin-type	130:139	arg1	O-glycosylation					141:155	Mucin-type O-glycosylation	130:155	Mucin-type O-glycosylation (O-glycans, O-glycome)	130:178	Mucin-type O-glycosylation (O-glycans, O-glycome) is among the most biologically important post-translational modification in glycoproteins but O-glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods.
34101390	7	67	theme	Current	965:971	arg1	Protocols					973:981	Current Protocols	965:981	Current Protocols	965:981	Current Protocols published by Wiley Periodicals LLC.
34101390	9	68	dep	reporter/amplification	1135:1156	arg1	Protocol					1223:1230	Basic Protocol 2	1217:1232	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	0	69	theme	Preparative	65:75	arg1	Tools					77:81	Analytical and Preparative Tools	50:81	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.	0:128	Cellular O-Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin-Type O-Glycans of Living Cells.
34101390	3	70	theme	glycans	705:711	arg1	types					687:691	all types	683:691	all types of O-GalNAc glycans representative of the cells' capabilities	683:753	Living cells metabolically convert these precursors to all types of O-GalNAc glycans representative of the cells' capabilities.
34101390	9	71	theme	Basic	1217:1221	arg1	Protocol					1223:1230	Basic Protocol 2	1217:1232	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	72	theme	MALDI-TOF/MS	1466:1477	arg1	identification					1479:1492	MALDI-TOF/MS identification	1466:1492	MALDI-TOF/MS identification	1466:1492	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	73	theme	PYAB-Bn-O-glycan	1508:1523	arg1	purification					1449:1460	2D-HPLC purification	1441:1460	2D-HPLC purification	1441:1460	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	73	theme	PYAB-Bn-O-glycan	1508:1523	arg1	identification					1479:1492	MALDI-TOF/MS identification	1466:1492	MALDI-TOF/MS identification	1466:1492	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	4	74	theme	functional	853:862	arg1	studies					864:870	functional studies	853:870	functional studies	853:870	The amplification and secretion of the O-glycome products greatly facilitates their analysis and functional studies.
34101390	9	75	from	cells	1281:1285	arg1	Preparation					1235:1245	Preparation	1235:1245	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.	1098:1524	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	75	from	cells	1281:1285	arg1	O-glycans					1259:1267	cellular O-glycans	1250:1267	cellular O-glycans from living cells	1250:1285	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	76	dep	glycomics	1302:1310	arg1	Protocol					1341:1348	Basic Protocol 3	1335:1350	Basic Protocol 3	1335:1350	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	9	77	with	Conjugation	1353:1363	arg1	Protocol					1429:1436	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	a bifunctional fluorescent tag Basic Protocol 4	1392:1438	Basic Protocol 1: Cellular O-glycome reporter/amplification for the analysis of mucin-type O-glycans from living cells Basic Protocol 2: Preparation of cellular O-glycans from living cells for functional glycomics and glycan microarrays Basic Protocol 3: Conjugation of cellular O-glycans with a bifunctional fluorescent tag Basic Protocol 4: 2D-HPLC purification and MALDI-TOF/MS identification of individual PYAB-Bn-O-glycan.
34101390	6	78	dep	Authors	956:962	arg1	2021					947:950	© 2021	945:950	© 2021	945:950	© 2021 The Authors.
33998969	2	0	theme	promising	494:502	arg1	prospects					504:512	promising prospects	494:512	promising prospects in treatment	494:525	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	1	1	dep	residue	287:293	arg1	sequon					262:267	AsnXxxThr/Ser sequon	248:267	AsnXxxThr/Ser sequon	248:267	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	10	2	theme	tedious	1528:1534	arg1	researches					1564:1573	tedious and time-wasting laboratory researches	1528:1573	tedious and time-wasting laboratory researches of the mutants.Communicated	1528:1601	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	9	3	theme	eligible	1392:1399	arg1	analogs					1424:1430	eligible FSH hyper-glycosylated analogs	1392:1430	eligible FSH hyper-glycosylated analogs	1392:1430	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	9	3	theme	eligible	1392:1399	arg1	mutants					1337:1343	2 mutants	1335:1343	2 mutants with a further glycan site	1335:1370	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	1	4	theme	carbohydrate	162:173	arg1	molecules					175:183	the carbohydrate molecules	158:183	the carbohydrate molecules	158:183	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	1	5	theme	AsnXxxThr/Ser	248:260	arg1	sequon					262:267	AsnXxxThr/Ser sequon	248:267	AsnXxxThr/Ser sequon	248:267	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	0	6	theme	bioinformatics	84:97	arg1	approach					99:106	a bioinformatics approach	82:106	a bioinformatics approach	82:106	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	0	6	theme	bioinformatics	84:97	arg1	analogs					73:79	hyper-glycosylated human follicle-stimulating hormone analogs	19:79	hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	19:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	9	7	theme	glycan	1360:1365	arg1	site					1367:1370	a further glycan site	1350:1370	a further glycan site	1350:1370	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	10	8	theme	laboratory	1553:1562	arg1	researches					1564:1573	tedious and time-wasting laboratory researches	1528:1573	tedious and time-wasting laboratory researches of the mutants.Communicated	1528:1601	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	2	9	from	Introduction	312:323	arg1	protein					397:403	the protein	393:403	the protein	393:403	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	2	10	theme	N-linked	339:346	arg1	site					362:365	additional N-linked glycosylation site	328:365	additional N-linked glycosylation site	328:365	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	8	11	theme	validation	1227:1236	arg1	techniques					1238:1247	The model validation techniques	1217:1247	The model validation techniques	1217:1247	The model validation techniques were used to examine 3-dimensional structures of the chosen mutant proteins.
33998969	10	12	theme	in	1496:1497	arg1	approach					1506:1513	Our in silico approach	1492:1513	Our in silico approach	1492:1513	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	3	13	theme	used	560:563	arg1	strategy					565:572	a favorably used strategy	548:572	a favorably used strategy to design	548:582	Glycoengineering is a favorably used strategy to design and generate hyper-glycosylated variants.
33998969	3	13	theme	used	560:563	arg1	Glycoengineering					528:543	Glycoengineering	528:543	Glycoengineering	528:543	Glycoengineering is a favorably used strategy to design and generate hyper-glycosylated variants.
33998969	8	14	theme	model	1221:1225	arg1	techniques					1238:1247	The model validation techniques	1217:1247	The model validation techniques	1217:1247	The model validation techniques were used to examine 3-dimensional structures of the chosen mutant proteins.
33998969	2	15	theme	glycosylation	348:360	arg1	site					362:365	additional N-linked glycosylation site	328:365	additional N-linked glycosylation site	328:365	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	9	16	with	mutants	1337:1343	arg1	site					1367:1370	a further glycan site	1350:1370	a further glycan site	1350:1370	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	6	17	theme	N-glycan	1038:1045	arg1	positions					1047:1055	novel N-glycan positions	1032:1055	novel N-glycan positions	1032:1055	We analyzed the amino acid chain of FSH to find out the proper locations to introduce asparagine and/or threonine for creating novel N-glycan positions.
33998969	5	18	theme	rational	771:778	arg1	strategy					794:801	A rational computational strategy	769:801	A rational computational strategy	769:801	A rational computational strategy was applied to predict functional/structural variations induced through changes in polypeptide chain.
33998969	2	19	link	N-linked	339:346	arg1	site					362:365	additional N-linked glycosylation site	328:365	additional N-linked glycosylation site	328:365	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	5	20	theme	functional/structural	826:846	arg1	variations					848:857	functional/structural variations	826:857	functional/structural variations induced through changes in polypeptide chain	826:902	A rational computational strategy was applied to predict functional/structural variations induced through changes in polypeptide chain.
33998969	5	21	theme	computational	780:792	arg1	strategy					794:801	A rational computational strategy	769:801	A rational computational strategy	769:801	A rational computational strategy was applied to predict functional/structural variations induced through changes in polypeptide chain.
33998969	6	22	theme	FSH	941:943	arg1	chain					932:936	the amino acid chain	917:936	the amino acid chain of FSH	917:943	We analyzed the amino acid chain of FSH to find out the proper locations to introduce asparagine and/or threonine for creating novel N-glycan positions.
33998969	7	23	theme	adequate	1161:1168	arg1	ones					1170:1173	then the eight adequate ones	1146:1173	then the eight adequate ones	1146:1173	This analysis resulted in the recognition of 40 possible N-glycosylation positions, and then the eight adequate ones were chosen for additional investigation.
33998969	9	24	theme	subsequent	1459:1468	arg1	studies					1483:1489	subsequent experimental studies	1459:1489	subsequent experimental studies	1459:1489	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	8	25	theme	mutant	1309:1314	arg1	proteins					1316:1323	the chosen mutant proteins	1298:1323	the chosen mutant proteins	1298:1323	The model validation techniques were used to examine 3-dimensional structures of the chosen mutant proteins.
33998969	5	26	from	changes	875:881	arg1	chain					898:902	polypeptide chain	886:902	polypeptide chain	886:902	A rational computational strategy was applied to predict functional/structural variations induced through changes in polypeptide chain.
33998969	10	27	theme	time-wasting	1540:1551	arg1	researches					1564:1573	tedious and time-wasting laboratory researches	1528:1573	tedious and time-wasting laboratory researches of the mutants.Communicated	1528:1601	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	9	28	theme	FSH	1401:1403	arg1	analogs					1424:1430	eligible FSH hyper-glycosylated analogs	1392:1430	eligible FSH hyper-glycosylated analogs	1392:1430	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	9	28	theme	FSH	1401:1403	arg1	mutants					1337:1343	2 mutants	1335:1343	2 mutants with a further glycan site	1335:1370	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	0	29	theme	Rational	0:7	arg1	design					9:14	Rational design	0:14	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	0:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	6	30	theme	novel	1032:1036	arg1	positions					1047:1055	novel N-glycan positions	1032:1055	novel N-glycan positions	1032:1055	We analyzed the amino acid chain of FSH to find out the proper locations to introduce asparagine and/or threonine for creating novel N-glycan positions.
33998969	8	31	theme	proteins	1316:1323	arg1	structures					1284:1293	3-dimensional structures	1270:1293	3-dimensional structures of the chosen mutant proteins	1270:1323	The model validation techniques were used to examine 3-dimensional structures of the chosen mutant proteins.
33998969	7	32	theme	positions	1131:1139	arg1	recognition					1088:1098	the recognition	1084:1098	the recognition of 40 possible N-glycosylation positions	1084:1139	This analysis resulted in the recognition of 40 possible N-glycosylation positions, and then the eight adequate ones were chosen for additional investigation.
33998969	1	33	theme	Asn	197:199	arg1	acid					207:210	the Asn amino acid	193:210	the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro)	193:309	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	0	34	theme	hyper-glycosylated	19:36	arg1	approach					99:106	a bioinformatics approach	82:106	a bioinformatics approach	82:106	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	0	34	theme	hyper-glycosylated	19:36	arg1	analogs					73:79	hyper-glycosylated human follicle-stimulating hormone analogs	19:79	hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	19:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	9	35	theme	hyper-glycosylated	1405:1422	arg1	analogs					1424:1430	eligible FSH hyper-glycosylated analogs	1392:1430	eligible FSH hyper-glycosylated analogs	1392:1430	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	9	35	theme	hyper-glycosylated	1405:1422	arg1	mutants					1337:1343	2 mutants	1335:1343	2 mutants with a further glycan site	1335:1370	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	8	36	theme	3-dimensional	1270:1282	arg1	structures					1284:1293	3-dimensional structures	1270:1293	3-dimensional structures of the chosen mutant proteins	1270:1323	The model validation techniques were used to examine 3-dimensional structures of the chosen mutant proteins.
33998969	1	37	theme	amino	201:205	arg1	acid					207:210	the Asn amino acid	193:210	the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro)	193:309	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	5	38	theme	polypeptide	886:896	arg1	chain					898:902	polypeptide chain	886:902	polypeptide chain	886:902	A rational computational strategy was applied to predict functional/structural variations induced through changes in polypeptide chain.
33998969	10	39	theme	mutants.Communicated	1582:1601	arg1	researches					1564:1573	tedious and time-wasting laboratory researches	1528:1573	tedious and time-wasting laboratory researches of the mutants.Communicated	1528:1601	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	1	40	dep	sequence	238:245	arg1	residue					287:293	any residue	283:293	any residue	283:293	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	6	41	theme	proper	961:966	arg1	locations					968:976	the proper locations	957:976	the proper locations	957:976	We analyzed the amino acid chain of FSH to find out the proper locations to introduce asparagine and/or threonine for creating novel N-glycan positions.
33998969	4	42	theme	follicle-stimulating	650:669	arg1	HuFSH					680:684	HuFSH	680:684	HuFSH	680:684	In this research, human follicle-stimulating hormone (HuFSH) was considered to identify appropriate positions for adding novel N-glycan sites.
33998969	4	42	theme	follicle-stimulating	650:669	arg1	hormone					671:677	human follicle-stimulating hormone	644:677	human follicle-stimulating hormone (HuFSH)	644:685	In this research, human follicle-stimulating hormone (HuFSH) was considered to identify appropriate positions for adding novel N-glycan sites.
33998969	0	43	theme	follicle-stimulating	44:63	arg1	hormone					65:71	human follicle-stimulating hormone	38:71	hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	19:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	7	44	theme	N-glycosylation	1115:1129	arg1	positions					1131:1139	40 possible N-glycosylation positions	1103:1139	40 possible N-glycosylation positions	1103:1139	This analysis resulted in the recognition of 40 possible N-glycosylation positions, and then the eight adequate ones were chosen for additional investigation.
33998969	6	45	theme	acid	927:930	arg1	chain					932:936	the amino acid chain	917:936	the amino acid chain of FSH	917:943	We analyzed the amino acid chain of FSH to find out the proper locations to introduce asparagine and/or threonine for creating novel N-glycan positions.
33998969	2	46	theme	proposed	372:379	arg1	location					381:388	proposed location	372:388	proposed location	372:388	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	7	47	theme	additional	1191:1200	arg1	investigation					1202:1214	additional investigation	1191:1214	additional investigation	1191:1214	This analysis resulted in the recognition of 40 possible N-glycosylation positions, and then the eight adequate ones were chosen for additional investigation.
33998969	0	48	theme	human	38:42	arg1	hormone					65:71	human follicle-stimulating hormone	38:71	hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	19:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	2	49	gly	glycosylation	348:360	arg2	site					362:365	additional N-linked glycosylation site	328:365	additional N-linked glycosylation site	328:365	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	6	50	theme	amino	921:925	arg1	chain					932:936	the amino acid chain	917:936	the amino acid chain of FSH	917:943	We analyzed the amino acid chain of FSH to find out the proper locations to introduce asparagine and/or threonine for creating novel N-glycan positions.
33998969	6	51	dep	find	948:951	arg1	out					953:955	out	953:955	out	953:955	We analyzed the amino acid chain of FSH to find out the proper locations to introduce asparagine and/or threonine for creating novel N-glycan positions.
33998969	3	52	gly	hyper-glycosylated	597:614	arg1	variants					616:623	hyper-glycosylated variants	597:623	hyper-glycosylated variants	597:623	Glycoengineering is a favorably used strategy to design and generate hyper-glycosylated variants.
33998969	0	53	theme	analogs	73:79	arg1	design					9:14	Rational design	0:14	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	0:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	2	54	from	prospects	504:512	arg1	treatment					517:525	treatment	517:525	treatment	517:525	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	3	55	theme	hyper-glycosylated	597:614	arg1	variants					616:623	hyper-glycosylated variants	597:623	hyper-glycosylated variants	597:623	Glycoengineering is a favorably used strategy to design and generate hyper-glycosylated variants.
33998969	10	56	theme	H.	1616:1617	arg1	Sharma					1619:1624	Ramaswamy H. Sharma	1606:1624	Ramaswamy H. Sharma	1606:1624	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	2	57	theme	additional	328:337	arg1	site					362:365	additional N-linked glycosylation site	328:365	additional N-linked glycosylation site	328:365	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	0	58	theme	hormone	65:71	arg1	approach					99:106	a bioinformatics approach	82:106	a bioinformatics approach	82:106	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	0	58	theme	hormone	65:71	arg1	analogs					73:79	hyper-glycosylated human follicle-stimulating hormone analogs	19:79	hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	19:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	7	59	theme	possible	1106:1113	arg1	positions					1131:1139	40 possible N-glycosylation positions	1103:1139	40 possible N-glycosylation positions	1103:1139	This analysis resulted in the recognition of 40 possible N-glycosylation positions, and then the eight adequate ones were chosen for additional investigation.
33998969	0	60	gly	hyper-glycosylated	19:36	arg1	approach					99:106	a bioinformatics approach	82:106	a bioinformatics approach	82:106	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	0	60	gly	hyper-glycosylated	19:36	arg1	analogs					73:79	hyper-glycosylated human follicle-stimulating hormone analogs	19:79	hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach)	19:107	Rational design of hyper-glycosylated human follicle-stimulating hormone analogs (a bioinformatics approach).
33998969	9	61	theme	further	1352:1358	arg1	site					1367:1370	a further glycan site	1350:1370	a further glycan site	1350:1370	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	1	62	theme	complex	131:137	arg1	mechanism					139:147	a complex mechanism	129:147	a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro)	129:309	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	1	62	theme	complex	131:137	arg1	N-glycosylation					110:124	N-glycosylation	110:124	N-glycosylation	110:124	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	4	63	theme	novel	747:751	arg1	sites					762:766	novel N-glycan sites	747:766	novel N-glycan sites	747:766	In this research, human follicle-stimulating hormone (HuFSH) was considered to identify appropriate positions for adding novel N-glycan sites.
33998969	1	64	from	acid	207:210	arg1	sequence					238:245	the N-glycan consensus sequence	215:245	the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro)	215:309	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	8	65	used	used	1254:1257	arg2	techniques					1238:1247	The model validation techniques	1217:1247	The model validation techniques	1217:1247	The model validation techniques were used to examine 3-dimensional structures of the chosen mutant proteins.
33998969	1	66	theme	N-glycan	219:226	arg1	sequence					238:245	the N-glycan consensus sequence	215:245	the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro)	215:309	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	10	67	theme	Ramaswamy	1606:1614	arg1	Sharma					1619:1624	Ramaswamy H. Sharma	1606:1624	Ramaswamy H. Sharma	1606:1624	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	9	68	gly	hyper-glycosylated	1405:1422	arg1	analogs					1424:1430	eligible FSH hyper-glycosylated analogs	1392:1430	eligible FSH hyper-glycosylated analogs	1392:1430	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	9	68	gly	hyper-glycosylated	1405:1422	arg1	mutants					1337:1343	2 mutants	1335:1343	2 mutants with a further glycan site	1335:1370	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	9	69	theme	experimental	1470:1481	arg1	studies					1483:1489	subsequent experimental studies	1459:1489	subsequent experimental studies	1459:1489	Finally, 2 mutants with a further glycan site were recommended as eligible FSH hyper-glycosylated analogs, which may be regarded for subsequent experimental studies.
33998969	4	70	theme	N-glycan	753:760	arg1	sites					762:766	novel N-glycan sites	747:766	novel N-glycan sites	747:766	In this research, human follicle-stimulating hormone (HuFSH) was considered to identify appropriate positions for adding novel N-glycan sites.
33998969	8	71	theme	chosen	1302:1307	arg1	proteins					1316:1323	the chosen mutant proteins	1298:1323	the chosen mutant proteins	1298:1323	The model validation techniques were used to examine 3-dimensional structures of the chosen mutant proteins.
33998969	1	72	theme	consensus	228:236	arg1	sequence					238:245	the N-glycan consensus sequence	215:245	the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro)	215:309	N-glycosylation is a complex mechanism in which the carbohydrate molecules bind to the Asn amino acid in the N-glycan consensus sequence (AsnXxxThr/Ser sequon, where Xxx is any residue, excluding Pro).
33998969	4	73	theme	appropriate	714:724	arg1	positions					726:734	appropriate positions	714:734	appropriate positions for adding novel N-glycan sites	714:766	In this research, human follicle-stimulating hormone (HuFSH) was considered to identify appropriate positions for adding novel N-glycan sites.
33998969	10	74	dep	in	1496:1497	arg1	silico					1499:1504	silico	1499:1504	silico	1499:1504	Our in silico approach may decrease tedious and time-wasting laboratory researches of the mutants.Communicated by Ramaswamy H. Sharma.
33998969	4	75	theme	human	644:648	arg1	HuFSH					680:684	HuFSH	680:684	HuFSH	680:684	In this research, human follicle-stimulating hormone (HuFSH) was considered to identify appropriate positions for adding novel N-glycan sites.
33998969	4	75	theme	human	644:648	arg1	hormone					671:677	human follicle-stimulating hormone	644:677	human follicle-stimulating hormone (HuFSH)	644:685	In this research, human follicle-stimulating hormone (HuFSH) was considered to identify appropriate positions for adding novel N-glycan sites.
33998969	2	76	theme	protein	459:465	arg1	characteristics					467:481	the protein characteristics	455:481	the protein characteristics	455:481	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
33998969	2	77	theme	site	362:365	arg1	Introduction					312:323	Introduction	312:323	Introduction of additional N-linked glycosylation site into proposed location in the protein	312:403	Introduction of additional N-linked glycosylation site into proposed location in the protein causes to its hyper-glycosylation and can enhance the protein characteristics to provide promising prospects in treatment.
31852790	12	0	theme	antibodies	2488:2497	arg1	elicitation					2450:2460	the elicitation	2446:2460	the elicitation of these broadly reactive antibodies	2446:2497	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	13	1	theme	HA	2530:2531	arg1	structures					2533:2542	the HA structures	2526:2542	the HA structures around the RBS	2526:2557	A better understanding of the HA structures around the RBS will lead to more effective HA immunogens.
31852790	9	2	from	position	1760:1767	arg1	lysine					1750:1755	a deleted lysine	1740:1755	a deleted lysine at position 147 residue	1740:1779	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	7	3	theme	influenza	1392:1400	arg1	viruses					1402:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	12	4	theme	Specific	2361:2368	arg1	sites					2377:2381	Specific glycan sites	2361:2381	Specific glycan sites	2361:2381	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	6	5	theme	HA	1210:1211	arg1	antigens					1213:1220	COBRA HA antigens	1204:1220	COBRA HA antigens	1204:1220	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	7	6	theme	pandemic-like	1373:1385	arg1	viruses					1402:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	9	7	theme	lysine	1750:1755	arg1	residue					1773:1779	a deleted lysine at position 147 residue	1740:1779	a deleted lysine at position 147 residue	1740:1779	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	3	8	dep	overcome	308:315	arg1	to					305:306	to	305:306	to	305:306	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	1	9	theme	influenza	170:178	arg1	infections					186:195	influenza virus infections	170:195	influenza virus infections	170:195	Vaccination is the most effective way to prevent influenza virus infections.
31852790	7	10	theme	seasonal-like	1355:1367	arg1	viruses					1402:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	4	11	theme	activity	666:673	arg1	patterns					620:627	differential patterns	607:627	differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses	607:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	13	12	theme	better	2502:2507	arg1	understanding					2509:2521	A better understanding	2500:2521	A better understanding of the HA structures around the RBS	2500:2557	A better understanding of the HA structures around the RBS will lead to more effective HA immunogens.
31852790	5	13	theme	Sb	839:840	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	13	theme	Sb	839:840	arg1	sites					852:856	Sb antigenic sites	839:856	Sb antigenic sites	839:856	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	10	14	dep	Advanced	2037:2044	arg1	head-based					2082:2091	head-based	2082:2091	head-based	2082:2091	Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses have been developed.
31852790	12	15	theme	molecule	2428:2435	arg1	tip					2414:2416	the tip	2410:2416	the tip of the HA molecule	2410:2435	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	13	16	theme	effective	2577:2585	arg1	immunogens					2590:2599	more effective HA immunogens	2572:2599	more effective HA immunogens	2572:2599	A better understanding of the HA structures around the RBS will lead to more effective HA immunogens.
31852790	9	17	theme	H1N1	1904:1907	arg1	viruses.IMPORTANCE					1919:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	4	18	theme	inhibition	649:658	arg1	activity					666:673	hemagglutination inhibition (HAI) activity	632:673	hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses	632:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	12	19	from	tip	2414:2416	arg1	located					2399:2405	located	2399:2405	located	2399:2405	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	8	20	from	residues	1461:1468	arg1	region					1490:1495	the Sa antigenic region	1473:1495	the Sa antigenic region	1473:1495	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	6	21	theme	designated	1181:1190	arg1	V1					1192:1193	designated V1	1181:1193	designated V1 to V12	1181:1200	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	13	22	dep	effective	2577:2585	arg1	HA					2587:2588	HA	2587:2588	HA	2587:2588	A better understanding of the HA structures around the RBS will lead to more effective HA immunogens.
31852790	4	23	theme	influenza	699:707	arg1	viruses					709:715	H1N1 influenza viruses	694:715	H1N1 influenza viruses	694:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	6	24	theme	antigens	1239:1246	arg1	antigens					1239:1246	wild-type HA antigens	1226:1246	wild-type HA antigens	1226:1246	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	24	theme	antigens	1239:1246	arg1	one					1145:1147	one	1145:1147	one	1145:1147	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	24	theme	antigens	1239:1246	arg1	antigens					1171:1178	the 12 modified HA antigens	1152:1178	the 12 modified HA antigens (designated V1 to V12)	1152:1201	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	24	theme	antigens	1239:1246	arg1	antigens					1213:1220	COBRA HA antigens	1204:1220	COBRA HA antigens	1204:1220	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	9	25	gly	glycosylation	1702:1714	arg2	residue					1724:1730	residue 144	1724:1734	residue 144	1724:1734	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	9	25	gly	glycosylation	1702:1714	arg2	site					1716:1719	a glycosylation site	1700:1719	a glycosylation site at residue 144	1700:1734	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	5	26	theme	pandemic-like	879:891	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	9	27	theme	HA	1676:1677	arg1	antigens					1679:1686	HA antigens	1676:1686	HA antigens that lacked a glycosylation site at residue 144	1676:1734	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	7	28	theme	hemagglutination	1288:1303	arg1	activity					1316:1323	hemagglutination inhibition activity	1288:1323	hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses	1288:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	6	29	theme	antigens	1171:1178	arg1	antigens					1239:1246	wild-type HA antigens	1226:1246	wild-type HA antigens	1226:1246	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	29	theme	antigens	1171:1178	arg1	one					1145:1147	one	1145:1147	one	1145:1147	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	29	theme	antigens	1171:1178	arg1	antigens					1171:1178	the 12 modified HA antigens	1152:1178	the 12 modified HA antigens (designated V1 to V12)	1152:1201	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	29	theme	antigens	1171:1178	arg1	antigens					1213:1220	COBRA HA antigens	1204:1220	COBRA HA antigens	1204:1220	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	10	30	theme	H1N1	2144:2147	arg1	viruses					2159:2165	H1N1 influenza viruses	2144:2165	H1N1 influenza viruses	2144:2165	Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses have been developed.
31852790	6	31	dep	antigens	1171:1178	arg1	V1					1192:1193	designated V1	1181:1193	designated V1 to V12	1181:1200	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	32	theme	wild-type	1226:1234	arg1	antigens					1239:1246	wild-type HA antigens	1226:1246	wild-type HA antigens	1226:1246	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	8	33	theme	glycosylation	1437:1449	arg1	sites					1451:1455	glycosylation sites	1437:1455	glycosylation sites	1437:1455	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	6	34	theme	modified	1159:1166	arg1	antigens					1171:1178	the 12 modified HA antigens	1152:1178	the 12 modified HA antigens (designated V1 to V12)	1152:1201	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	9	35	theme	great	1949:1953	arg1	need					1955:1958	a great need	1947:1958	a great need to develop broadly reactive or universal vaccines against influenza viruses	1947:2034	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	2	36	theme	isolates	247:254	arg1	diversity					211:219	the diversity	207:219	the diversity of antigenically distinct isolates	207:254	However, the diversity of antigenically distinct isolates is a challenge for vaccine development.
31852790	2	36	theme	isolates	247:254	arg1	challenge					261:269	a challenge	259:269	a challenge for vaccine development	259:293	However, the diversity of antigenically distinct isolates is a challenge for vaccine development.
31852790	1	37	theme	effective	145:153	arg1	way					155:157	the most effective way	136:157	the most effective way to prevent influenza virus infections	136:195	Vaccination is the most effective way to prevent influenza virus infections.
31852790	1	37	theme	effective	145:153	arg1	Vaccination					121:131	Vaccination	121:131	Vaccination	121:131	Vaccination is the most effective way to prevent influenza virus infections.
31852790	12	38	theme	HA	2425:2426	arg1	molecule					2428:2435	the HA molecule	2421:2435	the HA molecule	2421:2435	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	5	39	theme	HA	758:759	arg1	antigens					761:768	these HA antigens	752:768	these HA antigens	752:768	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	40	theme	seasonal-like	861:873	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	3	41	theme	protective	359:368	arg1	efficacy					370:377	the protective efficacy	355:377	the protective efficacy of influenza vaccines	355:399	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	7	42	theme	inhibition	1305:1314	arg1	activity					1316:1323	hemagglutination inhibition activity	1288:1323	hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses	1288:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	0	43	theme	H1N1	88:91	arg1	Virus					103:107	H1N1 Influenza Virus	88:107	Broadly Reactive H1N1 Influenza Virus Antibodies	71:118	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	5	44	theme	antibody	1062:1069	arg1	profile					1071:1077	the elicited antibody profile	1049:1077	the elicited antibody profile	1049:1077	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	8	45	theme	Sa	1477:1478	arg1	region					1490:1495	the Sa antigenic region	1473:1495	the Sa antigenic region	1473:1495	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	11	46	theme	antibodies	2349:2358	arg1	elicitation					2311:2321	elicitation	2311:2321	elicitation of these broadly reactive antibodies	2311:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	0	47	theme	Virus	103:107	arg1	Antibodies					109:118	Broadly Reactive H1N1 Influenza Virus Antibodies	71:118	Broadly Reactive H1N1 Influenza Virus Antibodies	71:118	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	3	48	theme	vaccines	392:399	arg1	efficacy					370:377	the protective efficacy	355:377	the protective efficacy of influenza vaccines	355:399	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	0	49	from	Residue	26:32	arg1	Hemagglutinin					37:49	Hemagglutinin	37:49	Hemagglutinin	37:49	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	11	50	theme	amino	2237:2241	arg1	acids					2243:2247	the specific amino acids	2224:2247	the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies	2224:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	0	51	theme	N-Linked	0:7	arg1	Glycans					9:15	N-Linked Glycans	0:15	N-Linked Glycans	0:15	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	5	52	theme	HA	912:913	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	7	53	theme	elicited	1253:1260	arg1	antisera					1262:1269	The elicited antisera	1249:1269	The elicited antisera	1249:1269	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	9	54	theme	deleted	1742:1748	arg1	lysine					1750:1755	a deleted lysine	1740:1755	a deleted lysine at position 147 residue	1740:1779	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	4	55	theme	COBRA	552:556	arg1	X6					578:579	X6	578:579	X6	578:579	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	4	55	theme	COBRA	552:556	arg1	P1					571:572	P1	571:572	P1	571:572	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	4	55	theme	COBRA	552:556	arg1	vaccines					561:568	Two candidate COBRA HA vaccines	538:568	Two candidate COBRA HA vaccines	538:568	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	9	56	theme	influenza	2018:2026	arg1	viruses					2028:2034	influenza viruses	2018:2034	influenza viruses	2018:2034	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	9	57	from	residue	1724:1730	arg1	site					1716:1719	a glycosylation site	1700:1719	a glycosylation site at residue 144	1700:1734	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	8	58	theme	receptor	1509:1516	arg1	RBS					1532:1534	RBS	1532:1534	RBS	1532:1534	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	8	58	theme	receptor	1509:1516	arg1	site					1526:1529	the receptor binding site	1505:1529	the receptor binding site (RBS)	1505:1535	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	8	59	from	region	1490:1495	arg1	signatures					1548:1557	signatures	1548:1557	signatures for the elicitation of broadly reactive antibodies by these HA immunogens	1548:1631	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	8	59	from	region	1490:1495	arg1	pattern					1426:1432	the pattern	1422:1432	the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS),	1422:1536	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	5	60	theme	reactive	785:792	arg1	responses					801:809	broadly reactive immune responses	777:809	broadly reactive immune responses	777:809	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	61	dep	Cb	828:829	arg1	the					824:826	the	824:826	the	824:826	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	3	62	theme	antigens	497:504	arg1	development					439:449	the development	435:449	the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA)	435:535	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	3	63	dep	optimized	470:478	arg1	reactive					488:495	reactive	488:495	reactive	488:495	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	12	64	theme	glycan	2370:2375	arg1	sites					2377:2381	Specific glycan sites	2361:2381	Specific glycan sites	2361:2381	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	8	65	theme	antibodies	1599:1608	arg1	elicitation					1567:1577	the elicitation	1563:1577	the elicitation of broadly reactive antibodies by these HA immunogens	1563:1631	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	5	66	theme	HA	976:977	arg1	proteins					979:986	the COBRA HA proteins	966:986	the COBRA HA proteins	966:986	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	67	from	regions	955:961	arg1	proteins					979:986	the COBRA HA proteins	966:986	the COBRA HA proteins	966:986	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	6	68	theme	antigens	1213:1220	arg1	antigens					1239:1246	wild-type HA antigens	1226:1246	wild-type HA antigens	1226:1246	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	68	theme	antigens	1213:1220	arg1	one					1145:1147	one	1145:1147	one	1145:1147	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	68	theme	antigens	1213:1220	arg1	antigens					1171:1178	the 12 modified HA antigens	1152:1178	the 12 modified HA antigens (designated V1 to V12)	1152:1201	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	68	theme	antigens	1213:1220	arg1	antigens					1213:1220	COBRA HA antigens	1204:1220	COBRA HA antigens	1204:1220	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	11	69	from	elicitation	2311:2321	arg1	important					2298:2306	important	2298:2306	important	2298:2306	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	11	69	from	elicitation	2311:2321	arg1	site					2277:2280	the receptor binding site	2256:2280	the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies	2256:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	7	70	theme	viruses	1402:1408	arg1	panel					1335:1339	a panel	1333:1339	a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses	1333:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	11	71	theme	receptor	2260:2267	arg1	important					2298:2306	important	2298:2306	important	2298:2306	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	11	71	theme	receptor	2260:2267	arg1	RBS					2283:2285	RBS	2283:2285	RBS	2283:2285	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	11	71	theme	receptor	2260:2267	arg1	site					2277:2280	the receptor binding site	2256:2280	the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies	2256:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	6	72	theme	COBRA	1204:1208	arg1	antigens					1213:1220	COBRA HA antigens	1204:1220	COBRA HA antigens	1204:1220	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	2	73	theme	vaccine	275:281	arg1	development					283:293	vaccine development	275:293	vaccine development	275:293	However, the diversity of antigenically distinct isolates is a challenge for vaccine development.
31852790	7	74	theme	H1N1	1387:1390	arg1	viruses					1402:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	12	75	theme	reactive	2479:2486	arg1	antibodies					2488:2497	these broadly reactive antibodies	2465:2497	these broadly reactive antibodies	2465:2497	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	9	76	theme	glycosylation	1702:1714	arg1	site					1716:1719	a glycosylation site	1700:1719	a glycosylation site at residue 144	1700:1734	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	1	77	theme	virus	180:184	arg1	infections					186:195	influenza virus infections	170:195	influenza virus infections	170:195	Vaccination is the most effective way to prevent influenza virus infections.
31852790	9	78	theme	pandemic-like	1872:1884	arg1	viruses.IMPORTANCE					1919:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	11	79	from	important	2298:2306	arg1	elicitation					2311:2321	elicitation	2311:2321	elicitation of these broadly reactive antibodies	2311:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	7	80	theme	historical	1344:1353	arg1	viruses					1402:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	historical seasonal-like and pandemic-like H1N1 influenza viruses	1344:1408	The elicited antisera was assessed for hemagglutination inhibition activity against a panel of historical seasonal-like and pandemic-like H1N1 influenza viruses.
31852790	9	81	theme	seasonal-like	1890:1902	arg1	viruses.IMPORTANCE					1919:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	2	82	theme	distinct	238:245	arg1	isolates					247:254	antigenically distinct isolates	224:254	antigenically distinct isolates	224:254	However, the diversity of antigenically distinct isolates is a challenge for vaccine development.
31852790	8	83	gly	glycosylation	1437:1449	arg2	sites					1451:1455	glycosylation sites	1437:1455	glycosylation sites	1437:1455	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	9	84	theme	influenza	1909:1917	arg1	viruses.IMPORTANCE					1919:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	4	85	theme	hemagglutination	632:647	arg1	HAI					661:663	HAI	661:663	HAI	661:663	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	4	85	theme	hemagglutination	632:647	arg1	inhibition					649:658	hemagglutination inhibition	632:658	hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses	632:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	8	86	from	sites	1451:1455	arg1	region					1490:1495	the Sa antigenic region	1473:1495	the Sa antigenic region	1473:1495	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	5	87	theme	elicited	1053:1060	arg1	profile					1071:1077	the elicited antibody profile	1049:1077	the elicited antibody profile	1049:1077	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	4	88	with	antibodies	591:600	arg1	patterns					620:627	differential patterns	607:627	differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses	607:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	10	89	theme	influenza	2149:2157	arg1	viruses					2159:2165	H1N1 influenza viruses	2144:2165	H1N1 influenza viruses	2144:2165	Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses have been developed.
31852790	4	90	theme	H1N1	694:697	arg1	viruses					709:715	H1N1 influenza viruses	694:715	H1N1 influenza viruses	694:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	6	91	theme	HA	1236:1237	arg1	antigens					1239:1246	wild-type HA antigens	1226:1246	wild-type HA antigens	1226:1246	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	5	92	theme	wild-type	893:901	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	8	93	theme	sites	1451:1455	arg1	signatures					1548:1557	signatures	1548:1557	signatures for the elicitation of broadly reactive antibodies by these HA immunogens	1548:1631	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	8	93	theme	sites	1451:1455	arg1	pattern					1426:1432	the pattern	1422:1432	the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS),	1422:1536	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	6	94	theme	HA	1168:1169	arg1	antigens					1171:1178	the 12 modified HA antigens	1152:1178	the 12 modified HA antigens (designated V1 to V12)	1152:1201	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	4	95	theme	viruses	709:715	arg1	panel					685:689	a panel	683:689	a panel of H1N1 influenza viruses	683:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	5	96	theme	antigenic	842:850	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	96	theme	antigenic	842:850	arg1	sites					852:856	Sb antigenic sites	839:856	Sb antigenic sites	839:856	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	8	97	theme	residues	1461:1468	arg1	signatures					1548:1557	signatures	1548:1557	signatures for the elicitation of broadly reactive antibodies by these HA immunogens	1548:1631	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	8	97	theme	residues	1461:1468	arg1	pattern					1426:1432	the pattern	1422:1432	the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS),	1422:1536	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	0	98	theme	Reactive	79:86	arg1	Antibodies					109:118	Broadly Reactive H1N1 Influenza Virus Antibodies	71:118	Broadly Reactive H1N1 Influenza Virus Antibodies	71:118	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	3	99	theme	antigenic	321:329	arg1	variability					331:341	the antigenic variability	317:341	the antigenic variability	317:341	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	0	100	from	Glycans	9:15	arg1	Hemagglutinin					37:49	Hemagglutinin	37:49	Hemagglutinin	37:49	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	0	101	theme	Influenza	93:101	arg1	Virus					103:107	H1N1 Influenza Virus	88:107	Broadly Reactive H1N1 Influenza Virus Antibodies	71:118	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	11	102	theme	reactive	2340:2347	arg1	antibodies					2349:2358	these broadly reactive antibodies	2326:2358	these broadly reactive antibodies	2326:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	8	103	theme	antigenic	1480:1488	arg1	region					1490:1495	the Sa antigenic region	1473:1495	the Sa antigenic region	1473:1495	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	9	104	theme	reactive	1979:1986	arg1	vaccines					2001:2008	broadly reactive or universal vaccines	1971:2008	broadly reactive or universal vaccines against influenza viruses	1971:2034	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	10	105	theme	protective	2114:2123	arg1	antibodies					2125:2134	protective antibodies	2114:2134	protective antibodies against H1N1 influenza viruses	2114:2165	Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses have been developed.
31852790	5	106	from	epitopes	812:819	arg1	Cb					828:829	Cb	828:829	Cb	828:829	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	106	from	epitopes	812:819	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	106	from	epitopes	812:819	arg1	sites					852:856	Sb antigenic sites	839:856	Sb antigenic sites	839:856	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	106	from	epitopes	812:819	arg1	Sa					832:833	Sa	832:833	Sa	832:833	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	107	theme	homologous	944:953	arg1	regions					955:961	homologous regions	944:961	homologous regions in the COBRA HA proteins	944:986	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	11	108	theme	specific	2228:2235	arg1	acids					2243:2247	the specific amino acids	2224:2247	the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies	2224:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	8	109	from	pattern	1426:1432	arg1	region					1490:1495	the Sa antigenic region	1473:1495	the Sa antigenic region	1473:1495	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	9	110	theme	universal	1991:1999	arg1	vaccines					2001:2008	broadly reactive or universal vaccines	1971:2008	broadly reactive or universal vaccines against influenza viruses	1971:2034	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	5	111	theme	immune	794:799	arg1	responses					801:809	broadly reactive immune responses	777:809	broadly reactive immune responses	777:809	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	112	theme	COBRA	906:910	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	4	113	theme	HA	558:559	arg1	X6					578:579	X6	578:579	X6	578:579	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	4	113	theme	HA	558:559	arg1	P1					571:572	P1	571:572	P1	571:572	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	4	113	theme	HA	558:559	arg1	vaccines					561:568	Two candidate COBRA HA vaccines	538:568	Two candidate COBRA HA vaccines	538:568	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	0	114	theme	K147	21:24	arg1	Residue					26:32	K147 Residue	21:32	K147 Residue	21:32	N-Linked Glycans and K147 Residue on Hemagglutinin Synergize To Elicit Broadly Reactive H1N1 Influenza Virus Antibodies.
31852790	5	115	theme	antigens	915:922	arg1	Cb					828:829	Cb	828:829	Cb	828:829	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	115	theme	antigens	915:922	arg1	antigens					915:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	seasonal-like and pandemic-like wild-type or COBRA HA antigens	861:922	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	115	theme	antigens	915:922	arg1	sites					852:856	Sb antigenic sites	839:856	Sb antigenic sites	839:856	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	5	115	theme	antigens	915:922	arg1	Sa					832:833	Sa	832:833	Sa	832:833	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	3	116	theme	influenza	382:390	arg1	vaccines					392:399	influenza vaccines	382:399	influenza vaccines	382:399	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	8	117	theme	binding	1518:1524	arg1	RBS					1532:1534	RBS	1532:1534	RBS	1532:1534	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	8	117	theme	binding	1518:1524	arg1	site					1526:1529	the receptor binding site	1505:1529	the receptor binding site (RBS)	1505:1535	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	11	118	theme	binding	2269:2275	arg1	important					2298:2306	important	2298:2306	important	2298:2306	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	11	118	theme	binding	2269:2275	arg1	RBS					2283:2285	RBS	2283:2285	RBS	2283:2285	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	11	118	theme	binding	2269:2275	arg1	site					2277:2280	the receptor binding site	2256:2280	the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies	2256:2358	This study focused on understanding the specific amino acids around the receptor binding site (RBS) that were important in elicitation of these broadly reactive antibodies.
31852790	13	119	theme	structures	2533:2542	arg1	understanding					2509:2521	A better understanding	2500:2521	A better understanding of the HA structures around the RBS	2500:2557	A better understanding of the HA structures around the RBS will lead to more effective HA immunogens.
31852790	12	120	theme	located	2399:2405	arg1	sites					2377:2381	Specific glycan sites	2361:2381	Specific glycan sites	2361:2381	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	12	121	theme	amino	2387:2391	arg1	acids					2393:2397	amino acids	2387:2397	amino acids	2387:2397	Specific glycan sites and amino acids located at the tip of the HA molecule enhanced the elicitation of these broadly reactive antibodies.
31852790	3	122	theme	optimized	470:478	arg1	COBRA					507:511	COBRA	507:511	COBRA	507:511	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	3	122	theme	optimized	470:478	arg1	antigens					497:504	computationally optimized broadly reactive antigens	454:504	computationally optimized broadly reactive antigens (COBRA)	454:512	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	6	123	theme	virus-like	1106:1115	arg1	VLPs					1128:1131	VLPs	1128:1131	VLPs	1128:1131	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	6	123	theme	virus-like	1106:1115	arg1	particles					1117:1125	virus-like particles	1106:1125	virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens	1106:1246	Mice were vaccinated with virus-like particles (VLPs) expressing one of the 12 modified HA antigens (designated V1 to V12), COBRA HA antigens, or wild-type HA antigens.
31852790	3	124	theme	research	406:413	arg1	group					415:419	our research group	402:419	our research group	402:419	In order to overcome the antigenic variability and improve the protective efficacy of influenza vaccines, our research group has pioneered the development of computationally optimized broadly reactive antigens (COBRA) for hemagglutinin (HA).
31852790	4	125	theme	candidate	542:550	arg1	X6					578:579	X6	578:579	X6	578:579	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	4	125	theme	candidate	542:550	arg1	P1					571:572	P1	571:572	P1	571:572	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	4	125	theme	candidate	542:550	arg1	vaccines					561:568	Two candidate COBRA HA vaccines	538:568	Two candidate COBRA HA vaccines	538:568	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	9	126	with	infection	1857:1865	arg1	viruses.IMPORTANCE					1919:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE	1872:1936	Mice were vaccinated with VLPs expressing HA antigens that lacked a glycosylation site at residue 144 and a deleted lysine at position 147 residue were more effective at protecting against morbidity and mortality following infection with pandemic-like and seasonal-like H1N1 influenza viruses.IMPORTANCE There is a great need to develop broadly reactive or universal vaccines against influenza viruses.
31852790	8	127	theme	reactive	1590:1597	arg1	antibodies					1599:1608	broadly reactive antibodies	1582:1608	broadly reactive antibodies	1582:1608	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
31852790	10	128	theme	Advanced	2037:2044	arg1	vaccines					2093:2100	Advanced, next-generation hemagglutinin (HA) head-based vaccines	2037:2100	Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses	2037:2165	Advanced, next-generation hemagglutinin (HA) head-based vaccines that elicit protective antibodies against H1N1 influenza viruses have been developed.
31852790	5	129	theme	COBRA	970:974	arg1	proteins					979:986	the COBRA HA proteins	966:986	the COBRA HA proteins	966:986	In order to better understand how these HA antigens elicit broadly reactive immune responses, epitopes in the Cb, Sa, or Sb antigenic sites of seasonal-like and pandemic-like wild-type or COBRA HA antigens were exchanged with homologous regions in the COBRA HA proteins to determine which regions and residues were responsible for the elicited antibody profile.
31852790	4	130	theme	differential	607:618	arg1	patterns					620:627	differential patterns	607:627	differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses	607:715	Two candidate COBRA HA vaccines, P1 and X6, elicited antibodies with differential patterns of hemagglutination inhibition (HAI) activity against a panel of H1N1 influenza viruses.
31852790	8	131	theme	HA	1619:1620	arg1	immunogens					1622:1631	these HA immunogens	1613:1631	these HA immunogens	1613:1631	Primarily, the pattern of glycosylation sites and residues in the Sa antigenic region, around the receptor binding site (RBS), served as signatures for the elicitation of broadly reactive antibodies by these HA immunogens.
34855283	0	0	theme	cholangiocarcinoma	91:108	arg1	signature					65:73	a novel signature	57:73	a novel signature of intrahepatic cholangiocarcinoma	57:108	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	0	0	theme	cholangiocarcinoma	91:108	arg1	LacdiNAc					45:52	elevated LacdiNAc	36:52	elevated LacdiNAc	36:52	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	2	1	from	HCC	306:308	arg1	different					291:299	different	291:299	different	291:299	Although ICC is clinically different from HCC, their molecular differences are still largely unclear.
34855283	4	2	theme	novel	605:609	arg1	algorithm					611:619	novel algorithm	605:619	novel algorithm	605:619	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	0	3	theme	intrahepatic	78:89	arg1	cholangiocarcinoma					91:108	intrahepatic cholangiocarcinoma	78:108	intrahepatic cholangiocarcinoma	78:108	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	6	4	theme	bisecting	926:934	arg1	glycans					936:942	several bi-antennary and/or bisecting glycans	898:942	several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC	898:985	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	3	5	theme	aberrant	509:516	arg1	N-glycosylation					532:546	their aberrant site-specific N-glycosylation	503:546	their aberrant site-specific N-glycosylation	503:546	In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.
34855283	8	6	theme	diagnostic	1520:1529	arg1	biomarkers					1531:1540	ICC diagnostic biomarkers	1516:1540	ICC diagnostic biomarkers	1516:1540	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	8	7	theme	novel	1387:1391	arg1	alterations					1402:1412	The novel N-glycan alterations	1383:1412	The novel N-glycan alterations uniquely detected in ICC	1383:1437	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	6	8	theme	bi-antennary	906:917	arg1	glycans					936:942	several bi-antennary and/or bisecting glycans	898:942	several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC	898:985	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	7	9	theme	LacdiNAc-containing	1128:1146	arg1	N-glycopeptides					1148:1162	almost all LacdiNAc-containing N-glycopeptides	1117:1162	almost all LacdiNAc-containing N-glycopeptides	1117:1162	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	7	10	from	histochemistry	1265:1278	arg1	ICC					1335:1337	ICC	1335:1337	ICC	1335:1337	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	4	11	theme	894	724:726	arg1	glycoproteins					728:740	894 glycoproteins	724:740	894 glycoproteins in ICC and HCC tumors	724:762	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	6	12	theme	several	898:904	arg1	glycans					936:942	several bi-antennary and/or bisecting glycans	898:942	several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC	898:985	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	7	13	gly	N-glycopeptides	1148:1162	arg2	N-glycopeptides					1148:1162	almost all LacdiNAc-containing N-glycopeptides	1117:1162	almost all LacdiNAc-containing N-glycopeptides	1117:1162	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	5	14	with	glycans	774:780	arg1	structures					824:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	Notably, glycans with uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures were distinguished from their isomeric glycans.
34855283	8	15	theme	N-glycan	1393:1400	arg1	alterations					1402:1412	The novel N-glycan alterations	1383:1412	The novel N-glycan alterations uniquely detected in ICC	1383:1437	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	4	16	theme	N-glycan	655:662	arg1	structures					664:673	486 N-glycan structures	651:673	486 N-glycan structures attached on 1235 glycosites	651:701	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	6	17	dep	glycans	936:942	arg1	addition					886:893	addition	886:893	addition	886:893	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	6	18	theme	LacdiNAc-containing	1000:1018	arg1	glycans					1057:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	8	19	theme	therapeutic	1543:1553	arg1	targets					1555:1561	therapeutic targets	1543:1561	therapeutic targets	1543:1561	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	0	20	theme	Precision	0:8	arg1	N-glycoproteomics					10:26	Precision N-glycoproteomics	0:26	Precision N-glycoproteomics	0:26	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	1	21	theme	intrahepatic	186:197	arg1	cholangiocarcinoma					199:216	intrahepatic cholangiocarcinoma	186:216	intrahepatic cholangiocarcinoma (ICC)	186:222	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	1	21	theme	intrahepatic	186:197	arg1	ICC					219:221	ICC	219:221	ICC	219:221	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	3	22	theme	precision	381:389	arg1	analysis					408:415	precision N-glycoproteomic analysis	381:415	precision N-glycoproteomic analysis	381:415	In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.
34855283	8	23	theme	targets	1555:1561	arg1	discovery					1503:1511	the discovery	1499:1511	the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations	1499:1591	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	7	24	theme	β1-4	1307:1310	arg1	transferases					1319:1330	β1-4 GalNAc transferases	1307:1330	β1-4 GalNAc transferases in ICC	1307:1337	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	8	25	theme	mechanism	1568:1576	arg1	investigations					1578:1591	mechanism investigations	1568:1591	mechanism investigations	1568:1591	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	2	26	theme	molecular	317:325	arg1	differences					327:337	their molecular differences	311:337	their molecular differences	311:337	Although ICC is clinically different from HCC, their molecular differences are still largely unclear.
34855283	7	27	theme	high	1288:1291	arg1	expression					1293:1302	the high expression	1284:1302	the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels	1284:1380	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	3	28	theme	N-glycoproteomic	391:406	arg1	analysis					408:415	precision N-glycoproteomic analysis	381:415	precision N-glycoproteomic analysis	381:415	In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.
34855283	4	29	theme	developed	568:576	arg1	methods					593:599	our newly developed glycoproteomic methods	558:599	our newly developed glycoproteomic methods	558:599	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	8	30	located	detected	1423:1430	arg2	alterations					1402:1412	The novel N-glycan alterations	1383:1412	The novel N-glycan alterations uniquely detected in ICC	1383:1437	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	8	30	located	detected	1423:1430	arg1	ICC					1435:1437	ICC	1435:1437	ICC	1435:1437	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	7	31	from	expression	1293:1302	arg1	ICC					1335:1337	ICC	1335:1337	ICC	1335:1337	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	1	32	theme	Primary	111:117	arg1	cancer					125:130	Primary liver cancer	111:130	Primary liver cancer	111:130	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	3	33	theme	ICC	439:441	arg1	tumors					451:456	both ICC and HCC tumors	434:456	tumors	451:456	In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.
34855283	0	34	theme	elevated	36:43	arg1	signature					65:73	a novel signature	57:73	a novel signature of intrahepatic cholangiocarcinoma	57:108	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	0	34	theme	elevated	36:43	arg1	LacdiNAc					45:52	elevated LacdiNAc	36:52	elevated LacdiNAc	36:52	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	5	35	theme	GalNAcβ1-4GlcNAc	806:821	arg1	structures					824:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	Notably, glycans with uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures were distinguished from their isomeric glycans.
34855283	8	36	theme	future	1471:1476	arg1	studies					1478:1484	future studies	1471:1484	future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations	1471:1591	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	1	37	theme	liver	119:123	arg1	cancer					125:130	Primary liver cancer	111:130	Primary liver cancer	111:130	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	7	38	theme	transferases	1319:1330	arg1	histochemistry					1265:1278	lectin histochemistry	1258:1278	lectin histochemistry	1258:1278	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	7	38	theme	transferases	1319:1330	arg1	expression					1293:1302	the high expression	1284:1302	the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels	1284:1380	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	7	39	from	transferases	1319:1330	arg1	ICC					1335:1337	ICC	1335:1337	ICC	1335:1337	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	7	40	theme	lectin	1258:1263	arg1	histochemistry					1265:1278	lectin histochemistry	1258:1278	lectin histochemistry	1258:1278	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	4	41	theme	1235	687:690	arg1	glycosites					692:701	1235 glycosites	687:701	1235 glycosites	687:701	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	7	42	theme	ICC	1181:1183	arg1	tumor					1185:1189	ICC tumor	1181:1189	ICC tumor	1181:1189	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	4	43	theme	glycoproteomic	578:591	arg1	methods					593:599	our newly developed glycoproteomic methods	558:599	our newly developed glycoproteomic methods	558:599	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	6	44	gly	core-fucosylated	1040:1055	arg1	glycans					1057:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	7	45	theme	HCC	1202:1204	arg1	tumor					1206:1210	HCC tumor	1202:1210	HCC tumor	1202:1210	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	4	46	theme	structures	664:673	arg1	total					642:646	a total	640:646	a total of 486 N-glycan structures attached on 1235 glycosites	640:701	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	6	47	theme	glycans	1057:1063	arg1	number					990:995	a number	988:995	a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	988:1063	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	5	48	theme	isomeric	865:872	arg1	glycans					874:880	their isomeric glycans	859:880	their isomeric glycans	859:880	Notably, glycans with uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures were distinguished from their isomeric glycans.
34855283	4	49	gly	glycoproteins	728:740	arg1	glycoproteins					728:740	894 glycoproteins	724:740	894 glycoproteins in ICC and HCC tumors	724:762	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	6	50	theme	tri-antennary	1021:1033	arg1	glycans					1057:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	6	51	theme	core-fucosylated	1040:1055	arg1	glycans					1057:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	LacdiNAc-containing, tri-antennary, and core-fucosylated glycans	1000:1063	In addition to several bi-antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc-containing, tri-antennary, and core-fucosylated glycans were uniquely increased in ICC.
34855283	0	52	theme	novel	59:63	arg1	signature					65:73	a novel signature	57:73	a novel signature of intrahepatic cholangiocarcinoma	57:108	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	0	52	theme	novel	59:63	arg1	LacdiNAc					45:52	elevated LacdiNAc	36:52	elevated LacdiNAc	36:52	Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.
34855283	7	53	from	levels	1375:1380	arg1	histochemistry					1265:1278	lectin histochemistry	1258:1278	lectin histochemistry	1258:1278	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	7	53	from	levels	1375:1380	arg1	expression					1293:1302	the high expression	1284:1302	the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels	1284:1380	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	4	54	attach	attached	675:682	arg3	glycosites					692:701	1235 glycosites	687:701	1235 glycosites	687:701	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	4	54	attach	attached	675:682	arg2	structures					664:673	486 N-glycan structures	651:673	486 N-glycan structures attached on 1235 glycosites	651:701	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	5	55	theme	LacdiNAc	796:803	arg1	structures					824:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	Notably, glycans with uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures were distinguished from their isomeric glycans.
34855283	8	56	theme	investigations	1578:1591	arg1	discovery					1503:1511	the discovery	1499:1511	the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations	1499:1591	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	7	57	theme	mRNA	1347:1350	arg1	levels					1375:1380	both mRNA and protein expression levels	1342:1380	both mRNA and protein expression levels	1342:1380	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	4	58	from	glycoproteins	728:740	arg1	ICC					745:747	ICC	745:747	ICC	745:747	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	4	58	from	glycoproteins	728:740	arg1	tumors					757:762	HCC tumors	753:762	HCC tumors	753:762	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	4	59	gly	glycosites	692:701	arg2	glycosites					692:701	1235 glycosites	687:701	1235 glycosites	687:701	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	7	60	theme	expression	1364:1373	arg1	levels					1375:1380	both mRNA and protein expression levels	1342:1380	both mRNA and protein expression levels	1342:1380	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	3	61	theme	paracancer	469:478	arg1	tissues					480:486	paracancer tissues	469:486	both ICC and HCC tumors as well as paracancer tissues	434:486	In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.
34855283	4	62	theme	HCC	753:755	arg1	tumors					757:762	HCC tumors	753:762	HCC tumors	753:762	By using our newly developed glycoproteomic methods and novel algorithm, termed 'StrucGP', a total of 486 N-glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors.
34855283	7	63	from	ICC	1335:1337	arg1	histochemistry					1265:1278	lectin histochemistry	1258:1278	lectin histochemistry	1258:1278	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	7	63	from	ICC	1335:1337	arg1	expression					1293:1302	the high expression	1284:1302	the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels	1284:1380	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	1	64	theme	hepatocellular	151:164	arg1	HCC					177:179	HCC	177:179	HCC	177:179	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	1	64	theme	hepatocellular	151:164	arg1	carcinoma					166:174	hepatocellular carcinoma	151:174	hepatocellular carcinoma (HCC)	151:180	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	1	65	theme	major	235:239	arg1	problem					255:261	a major global health problem	233:261	a major global health problem	233:261	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	8	66	theme	biomarkers	1531:1540	arg1	discovery					1503:1511	the discovery	1499:1511	the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations	1499:1591	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	7	67	theme	GalNAc	1312:1317	arg1	transferases					1319:1330	β1-4 GalNAc transferases	1307:1330	β1-4 GalNAc transferases in ICC	1307:1337	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	8	68	theme	valuable	1449:1456	arg1	resource					1458:1465	a valuable resource	1447:1465	a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations	1447:1591	The novel N-glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.
34855283	3	69	theme	site-specific	518:530	arg1	N-glycosylation					532:546	their aberrant site-specific N-glycosylation	503:546	their aberrant site-specific N-glycosylation	503:546	In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.
34855283	3	70	theme	HCC	447:449	arg1	tumors					451:456	both ICC and HCC tumors	434:456	tumors	451:456	In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.
34855283	1	71	theme	global	241:246	arg1	problem					255:261	a major global health problem	233:261	a major global health problem	233:261	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
34855283	5	72	theme	uncommon	787:794	arg1	structures					824:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures	787:833	Notably, glycans with uncommon LacdiNAc (GalNAcβ1-4GlcNAc) structures were distinguished from their isomeric glycans.
34855283	7	73	theme	protein	1356:1362	arg1	levels					1375:1380	both mRNA and protein expression levels	1342:1380	both mRNA and protein expression levels	1342:1380	More interestingly, almost all LacdiNAc-containing N-glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1-4 GalNAc transferases in ICC at both mRNA and protein expression levels.
34855283	1	74	theme	health	248:253	arg1	problem					255:261	a major global health problem	233:261	a major global health problem	233:261	Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem.
32035902	2	0	theme	GlcNAc	347:352	arg1	residue					354:360	the proximal GlcNAc residue	334:360	the proximal GlcNAc residue mediating this effect through an unknown mechanism	334:411	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	8	1	theme	receptor	1270:1277	arg1	complexes					1279:1287	RAMP-CTR amylin receptor complexes	1254:1287	RAMP-CTR amylin receptor complexes	1254:1287	The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor.
32035902	2	2	theme	proximal	338:345	arg1	residue					354:360	the proximal GlcNAc residue	334:360	the proximal GlcNAc residue mediating this effect through an unknown mechanism	334:411	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	6	3	theme	mass	873:876	arg1	spectrometry					878:889	Hydrogen-deuterium exchange mass spectrometry	845:889	Hydrogen-deuterium exchange mass spectrometry	845:889	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	3	4	dep	calcitonin-bound	464:479	arg1	GlcNAc-bearing					482:495	GlcNAc-bearing	482:495	GlcNAc-bearing	482:495	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	5	5	theme	N-glycan-free	713:725	arg1	ECD					727:729	hormone-bound, N-glycan-free ECD	698:729	ECD	727:729	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	6	6	theme	dynamics	905:912	arg1	simulations					914:924	molecular dynamics simulations	895:924	molecular dynamics simulations	895:924	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	3	7	theme	ECD	501:503	arg1	structures					443:452	two crystal structures	431:452	two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD	431:503	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	2	8	theme	hormone	312:318	arg1	affinity					320:327	calcitonin hormone affinity	301:327	calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism	301:411	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	5	9	theme	ECD	727:729	arg1	structure					685:693	a structure	683:693	a structure of hormone-bound, N-glycan-free ECD	683:729	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	6	10	theme	molecular	895:903	arg1	simulations					914:924	molecular dynamics simulations	895:924	molecular dynamics simulations	895:924	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	5	11	theme	static	810:815	arg1	snapshots					834:842	the static crystallographic snapshots	806:842	the static crystallographic snapshots	806:842	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	5	12	located	observed	794:801	arg1	snapshots					834:842	the static crystallographic snapshots	806:842	the static crystallographic snapshots	806:842	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	5	12	located	observed	794:801	arg2	dynamics					781:788	CTR dynamics	777:788	CTR dynamics not observed in the static crystallographic snapshots	777:842	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	2	13	theme	extracellular	265:277	arg1	domain					279:284	its extracellular domain	261:284	its extracellular domain (ECD)	261:290	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	2	13	theme	extracellular	265:277	arg1	ECD					287:289	ECD	287:289	ECD	287:289	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	6	14	theme	loop	1124:1127	arg1	flexibility					1077:1087	the peptide-binding site while increasing flexibility	1035:1087	the peptide-binding site while increasing flexibility of the peptide-binding site turret loop	1035:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	5	15	theme	CTR	777:779	arg1	dynamics					781:788	CTR dynamics	777:788	CTR dynamics not observed in the static crystallographic snapshots	777:842	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	8	16	theme	amylin	1263:1268	arg1	complexes					1279:1287	RAMP-CTR amylin receptor complexes	1254:1287	RAMP-CTR amylin receptor complexes	1254:1287	The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor.
32035902	6	17	theme	peptide-binding	1039:1053	arg1	flexibility					1077:1087	the peptide-binding site while increasing flexibility	1035:1087	the peptide-binding site while increasing flexibility of the peptide-binding site turret loop	1035:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	2	18	from	N-glycosylation	224:238	arg1	domain					279:284	its extracellular domain	261:284	its extracellular domain (ECD)	261:290	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	2	18	from	N-glycosylation	224:238	arg1	ECD					287:289	ECD	287:289	ECD	287:289	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	6	19	theme	turret	1117:1122	arg1	loop					1124:1127	the peptide-binding site turret loop	1092:1127	the peptide-binding site turret loop	1092:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	0	20	theme	Receptor	11:18	arg1	N-Glycosylation					20:34	Calcitonin Receptor N-Glycosylation	0:34	Calcitonin Receptor N-Glycosylation	0:34	Calcitonin Receptor N-Glycosylation Enhances Peptide Hormone Affinity by Controlling Receptor Dynamics.
32035902	3	21	attach	present	423:429	arg1	resolutions					524:534	1.78 and 2.85 Å resolutions	508:534	1.78 and 2.85 Å resolutions	508:534	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	3	21	attach	present	423:429	arg2	we					420:421	we	420:421	we	420:421	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	2	22	theme	calcitonin	301:310	arg1	hormone					312:318	calcitonin hormone	301:318	calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism	301:411	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	6	23	theme	site	1112:1115	arg1	loop					1124:1127	the peptide-binding site turret loop	1092:1127	the peptide-binding site turret loop	1092:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	0	24	theme	Calcitonin	0:9	arg1	N-Glycosylation					20:34	Calcitonin Receptor N-Glycosylation	0:34	Calcitonin Receptor N-Glycosylation	0:34	Calcitonin Receptor N-Glycosylation Enhances Peptide Hormone Affinity by Controlling Receptor Dynamics.
32035902	6	25	theme	exchange	864:871	arg1	spectrometry					878:889	Hydrogen-deuterium exchange mass spectrometry	845:889	Hydrogen-deuterium exchange mass spectrometry	845:889	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	6	26	theme	N130	991:994	arg1	GlcNAc					996:1001	the N130 GlcNAc	987:1001	the N130 GlcNAc	987:1001	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	1	27	theme	drug	181:184	arg1	target					186:191	a drug target	179:191	a drug target for osteoporosis and diabetes	179:221	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	27	theme	drug	181:184	arg1	receptor					161:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor	104:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR)	104:174	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	3	28	theme	2.85 Å	517:522	arg1	resolutions					524:534	1.78 and 2.85 Å resolutions	508:534	1.78 and 2.85 Å resolutions	508:534	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	2	29	with	affinity	320:327	arg1	residue					354:360	the proximal GlcNAc residue	334:360	the proximal GlcNAc residue mediating this effect through an unknown mechanism	334:411	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	3	30	theme	salmon	457:462	arg1	ECD					501:503	salmon calcitonin-bound, GlcNAc-bearing CTR ECD	457:503	salmon calcitonin-bound, GlcNAc-bearing CTR ECD	457:503	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	0	31	theme	Hormone	53:59	arg1	Affinity					61:68	Peptide Hormone Affinity	45:68	Peptide Hormone Affinity	45:68	Calcitonin Receptor N-Glycosylation Enhances Peptide Hormone Affinity by Controlling Receptor Dynamics.
32035902	3	32	theme	CTR	497:499	arg1	ECD					501:503	salmon calcitonin-bound, GlcNAc-bearing CTR ECD	457:503	salmon calcitonin-bound, GlcNAc-bearing CTR ECD	457:503	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	5	33	theme	crystallographic	817:832	arg1	snapshots					834:842	the static crystallographic snapshots	806:842	the static crystallographic snapshots	806:842	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	6	34	theme	peptide-binding	1096:1110	arg1	loop					1124:1127	the peptide-binding site turret loop	1092:1127	the peptide-binding site turret loop	1092:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	3	35	theme	crystal	435:441	arg1	structures					443:452	two crystal structures	431:452	two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD	431:503	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	2	36	gly	N-glycosylation	224:238	arg1	domain					279:284	its extracellular domain	261:284	its extracellular domain (ECD)	261:290	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	2	36	gly	N-glycosylation	224:238	arg1	asparagine					243:252	asparagine 130	243:256	asparagine 130	243:256	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	2	36	gly	N-glycosylation	224:238	arg1	ECD					287:289	ECD	287:289	ECD	287:289	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	6	37	theme	adjacent	975:982	arg1	β-sheet					967:973	a β-sheet	965:973	a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop	965:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	0	38	theme	Peptide	45:51	arg1	Affinity					61:68	Peptide Hormone Affinity	45:68	Peptide Hormone Affinity	45:68	Calcitonin Receptor N-Glycosylation Enhances Peptide Hormone Affinity by Controlling Receptor Dynamics.
32035902	6	39	theme	Hydrogen-deuterium	845:862	arg1	spectrometry					878:889	Hydrogen-deuterium exchange mass spectrometry	845:889	Hydrogen-deuterium exchange mass spectrometry	845:889	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	2	40	theme	unknown	395:401	arg1	mechanism					403:411	an unknown mechanism	392:411	an unknown mechanism	392:411	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	7	41	theme	ligand	1181:1186	arg1	on-rate					1188:1194	the ligand on-rate	1177:1194	the ligand on-rate	1177:1194	These changes due to N-glycosylation increased the ligand on-rate and decreased its off-rate.
32035902	9	42	theme	receptor	1423:1430	arg1	dynamics					1432:1439	receptor dynamics	1423:1439	receptor dynamics	1423:1439	These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics.
32035902	8	43	theme	RAMP-CTR	1254:1261	arg1	complexes					1279:1287	RAMP-CTR amylin receptor complexes	1254:1287	RAMP-CTR amylin receptor complexes	1254:1287	The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor.
32035902	9	44	theme	GPCR	1397:1400	arg1	function					1402:1409	GPCR function	1397:1409	GPCR function	1397:1409	These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics.
32035902	3	45	theme	glycan	569:574	arg1	effect					576:581	the glycan effect	565:581	the glycan effect	565:581	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	1	46	theme	protein-coupled	118:132	arg1	target					186:191	a drug target	179:191	a drug target for osteoporosis and diabetes	179:221	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	46	theme	protein-coupled	118:132	arg1	CTR					171:173	CTR	171:173	CTR	171:173	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	46	theme	protein-coupled	118:132	arg1	receptor					161:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor	104:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR)	104:174	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	5	47	theme	hormone-bound	698:710	arg1	ECD					727:729	hormone-bound, N-glycan-free ECD	698:729	ECD	727:729	Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots.
32035902	3	48	theme	effect	576:581	arg1	mechanism					552:560	the mechanism	548:560	the mechanism of the glycan effect	548:581	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	1	49	theme	receptor	134:141	arg1	target					186:191	a drug target	179:191	a drug target for osteoporosis and diabetes	179:221	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	49	theme	receptor	134:141	arg1	CTR					171:173	CTR	171:173	CTR	171:173	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	49	theme	receptor	134:141	arg1	receptor					161:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor	104:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR)	104:174	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	8	50	theme	CGRP	1327:1330	arg1	receptor					1332:1339	the related CGRP receptor	1315:1339	the related CGRP receptor	1315:1339	The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor.
32035902	3	51	theme	calcitonin-bound	464:479	arg1	ECD					501:503	salmon calcitonin-bound, GlcNAc-bearing CTR ECD	457:503	salmon calcitonin-bound, GlcNAc-bearing CTR ECD	457:503	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	6	52	theme	site while	1055:1064	arg1	flexibility					1077:1087	the peptide-binding site while increasing flexibility	1035:1087	the peptide-binding site while increasing flexibility of the peptide-binding site turret loop	1035:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	8	53	theme	glycan	1228:1233	arg1	effect					1235:1240	The glycan effect	1224:1240	The glycan effect	1224:1240	The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor.
32035902	1	54	theme	GPCR	144:147	arg1	target					186:191	a drug target	179:191	a drug target for osteoporosis and diabetes	179:221	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	54	theme	GPCR	144:147	arg1	CTR					171:173	CTR	171:173	CTR	171:173	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	54	theme	GPCR	144:147	arg1	receptor					161:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor	104:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR)	104:174	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	4	55	theme	N130	588:591	arg1	GlcNAc					593:598	The N130 GlcNAc	584:598	The N130 GlcNAc	584:598	The N130 GlcNAc does not contact the hormone.
32035902	0	56	theme	Receptor	85:92	arg1	Dynamics					94:101	Receptor Dynamics	85:101	Receptor Dynamics	85:101	Calcitonin Receptor N-Glycosylation Enhances Peptide Hormone Affinity by Controlling Receptor Dynamics.
32035902	6	57	theme	increasing	1066:1075	arg1	flexibility					1077:1087	the peptide-binding site while increasing flexibility	1035:1087	the peptide-binding site while increasing flexibility of the peptide-binding site turret loop	1035:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	2	58	theme	asparagine	243:252	arg1	N-glycosylation					224:238	N-glycosylation	224:238	N-glycosylation of asparagine 130 in its extracellular domain (ECD)	224:290	N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism.
32035902	3	59	theme	1.78	508:511	arg1	resolutions					524:534	1.78 and 2.85 Å resolutions	508:534	1.78 and 2.85 Å resolutions	508:534	Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect.
32035902	6	60	theme	N-terminal	1011:1020	arg1	α-helix					1022:1028	the N-terminal α-helix	1007:1028	the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop	1007:1127	Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop.
32035902	8	61	theme	related	1319:1325	arg1	receptor					1332:1339	the related CGRP receptor	1315:1339	the related CGRP receptor	1315:1339	The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor.
32035902	1	62	theme	calcitonin	150:159	arg1	target					186:191	a drug target	179:191	a drug target for osteoporosis and diabetes	179:221	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	62	theme	calcitonin	150:159	arg1	CTR					171:173	CTR	171:173	CTR	171:173	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
32035902	1	62	theme	calcitonin	150:159	arg1	receptor					161:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor	104:168	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR)	104:174	The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes.
33666655	6	0	theme	binding	1283:1289	arg1	changes					1291:1297	glycan expression and plasma protein binding changes	1246:1297	changes	1291:1297	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	5	1	theme	heightened	1183:1192	arg1	response					1213:1220	a heightened anti-glycan immune response	1181:1220	a heightened anti-glycan immune response	1181:1220	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	4	2	theme	α2,6	897:900	arg1	sialylation					902:912	α2,6 sialylation	897:912	α2,6 sialylation	897:912	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	5	3	from	patients	1135:1142	arg1	plasma					1123:1128	plasma	1123:1128	plasma from patients with sickle cell disease	1123:1167	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	5	4	theme	immune	1206:1211	arg1	response					1213:1220	a heightened anti-glycan immune response	1181:1220	a heightened anti-glycan immune response	1181:1220	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	4	5	theme	mass	855:858	arg1	spectrometry					860:871	mass spectrometry	855:871	mass spectrometry	855:871	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	7	6	theme	sickle	1466:1471	arg1	disease					1478:1484	sickle cell disease	1466:1484	sickle cell disease	1466:1484	Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets.
33666655	7	7	theme	detailed	1412:1419	arg1	insights					1421:1428	detailed insights	1412:1428	detailed insights into glycan changes associated with sickle cell disease	1412:1484	Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets.
33666655	3	8	theme	individuals	764:774	arg1	plasma					746:751	the plasma	742:751	the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait	742:834	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	1	9	theme	organ	177:181	arg1	infarction					183:192	organ infarction	177:192	organ infarction	177:192	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	4	10	theme	α2,3	932:935	arg1	sialylation					937:947	α2,3 sialylation	932:947	α2,3 sialylation	932:947	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	2	11	theme	sialic	284:289	arg1	acid					291:294	sialic acid	284:294	sialic acid levels	284:301	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	2	12	from	structures	484:493	arg1	disease					537:543	sickle cell disease	525:543	sickle cell disease	525:543	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	3	13	theme	sickle	794:799	arg1	disease					806:812	sickle cell disease	794:812	sickle cell disease	794:812	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	3	14	theme	patients	780:787	arg1	plasma					746:751	the plasma	742:751	the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait	742:834	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	6	15	theme	cell	1309:1312	arg1	disease					1314:1320	sickle cell disease	1302:1320	sickle cell disease	1302:1320	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	4	16	from	decrease	920:927	arg1	antigens					965:972	blood group antigens	953:972	blood group antigens	953:972	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	4	16	from	decrease	920:927	arg1	sialylation					902:912	α2,6 sialylation	897:912	α2,6 sialylation	897:912	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	4	16	from	decrease	920:927	arg1	sialylation					937:947	α2,3 sialylation	932:947	α2,3 sialylation	932:947	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	1	17	theme	inherited	117:125	arg1	disorder					135:142	an inherited genetic disorder	114:142	an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide	114:239	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	1	17	theme	inherited	117:125	arg1	disease					103:109	Sickle cell disease	91:109	Sickle cell disease	91:109	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	3	18	theme	sickle	818:823	arg1	trait					830:834	sickle cell trait	818:834	sickle cell trait	818:834	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	2	19	theme	Previous	242:249	arg1	studies					251:257	Previous studies	242:257	Previous studies	242:257	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	4	20	theme	red	987:989	arg1	cells					997:1001	red blood cells	987:1001	red blood cells	987:1001	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	0	21	theme	sickle	70:75	arg1	disease					82:88	sickle cell disease	70:88	sickle cell disease	70:88	Characterization and statistical modeling of glycosylation changes in sickle cell disease.
33666655	3	22	theme	glycan	624:629	arg1	arrays					631:636	glycan arrays	624:636	glycan arrays	624:636	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	3	23	located	found	733:737	arg2	glycoproteins					691:703	red blood cell glycoproteins	676:703	red blood cell glycoproteins	676:703	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	3	23	located	found	733:737	arg1	plasma					746:751	the plasma	742:751	the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait	742:834	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	4	24	from	increase	885:892	arg1	antigens					965:972	blood group antigens	953:972	blood group antigens	953:972	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	4	24	from	increase	885:892	arg1	sialylation					902:912	α2,6 sialylation	897:912	α2,6 sialylation	897:912	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	4	24	from	increase	885:892	arg1	sialylation					937:947	α2,3 sialylation	932:947	α2,3 sialylation	932:947	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	3	25	with	patients	780:787	arg1	disease					806:812	sickle cell disease	794:812	sickle cell disease	794:812	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	3	25	with	patients	780:787	arg1	trait					830:834	sickle cell trait	818:834	sickle cell trait	818:834	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	6	26	theme	plasma	1268:1273	arg1	changes					1291:1297	glycan expression and plasma protein binding changes	1246:1297	changes	1291:1297	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	4	27	theme	group	959:963	arg1	antigens					965:972	blood group antigens	953:972	blood group antigens	953:972	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	6	28	theme	ABO	1367:1369	arg1	expression					1383:1392	ABO blood group expression	1367:1392	ABO blood group expression	1367:1392	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	2	29	theme	sickle	525:530	arg1	disease					537:543	sickle cell disease	525:543	sickle cell disease	525:543	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	6	30	from	expression	1253:1262	arg1	disease					1314:1320	sickle cell disease	1302:1320	sickle cell disease	1302:1320	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	5	31	theme	Y	1094:1094	arg1	structures					1096:1105	Lewis Y structures	1088:1105	Lewis Y structures	1088:1105	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	2	32	theme	red	368:370	arg1	cells					378:382	stressed red blood cells	359:382	stressed red blood cells	359:382	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	5	33	theme	cell	1156:1159	arg1	disease					1161:1167	sickle cell disease	1149:1167	sickle cell disease	1149:1167	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	3	34	with	individuals	764:774	arg1	disease					806:812	sickle cell disease	794:812	sickle cell disease	794:812	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	3	34	with	individuals	764:774	arg1	trait					830:834	sickle cell trait	818:834	sickle cell trait	818:834	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	1	35	theme	cell	98:101	arg1	disorder					135:142	an inherited genetic disorder	114:142	an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide	114:239	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	1	35	theme	cell	98:101	arg1	disease					103:109	Sickle cell disease	91:109	Sickle cell disease	91:109	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	2	36	theme	terminal	415:422	arg1	structures					432:441	surface-exposed clustered terminal mannose structures	389:441	surface-exposed clustered terminal mannose structures mediating hemolysis	389:461	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	0	37	theme	statistical	21:31	arg1	modeling					33:40	statistical modeling	21:40	statistical modeling	21:40	Characterization and statistical modeling of glycosylation changes in sickle cell disease.
33666655	2	38	theme	glycan	477:482	arg1	structures					484:493	detailed glycan structures	468:493	detailed glycan structures	468:493	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	2	39	theme	surface-exposed	389:403	arg1	structures					432:441	surface-exposed clustered terminal mannose structures	389:441	surface-exposed clustered terminal mannose structures mediating hemolysis	389:461	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	3	40	theme	mass	643:646	arg1	spectrometry					648:659	mass spectrometry	643:659	mass spectrometry	643:659	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	2	41	theme	cell	329:332	arg1	sickling					334:341	red blood cell sickling	319:341	red blood cell sickling	319:341	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	3	42	gly	glycoproteins	691:703	arg1	glycoproteins					691:703	red blood cell glycoproteins	676:703	red blood cell glycoproteins	676:703	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	3	43	theme	cell	686:689	arg1	glycoproteins					691:703	red blood cell glycoproteins	676:703	red blood cell glycoproteins	676:703	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	2	44	theme	red	319:321	arg1	cell					329:332	red blood cell	319:332	red blood cell sickling	319:341	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	7	45	theme	potential	1507:1515	arg1	targets					1529:1535	potential therapeutic targets	1507:1535	potential therapeutic targets	1507:1535	Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets.
33666655	5	46	theme	Increased	1004:1012	arg1	binding					1014:1020	Increased binding	1004:1020	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures	1004:1105	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	3	47	theme	red	676:678	arg1	glycoproteins					691:703	red blood cell glycoproteins	676:703	red blood cell glycoproteins	676:703	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	1	48	theme	million	216:222	arg1	worldwide					231:239	13 million people worldwide	213:239	13 million people worldwide	213:239	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	7	49	dep	potential	1507:1515	arg1	therapeutic					1517:1527	therapeutic	1517:1527	therapeutic	1517:1527	Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets.
33666655	6	50	theme	protein	1275:1281	arg1	changes					1291:1297	glycan expression and plasma protein binding changes	1246:1297	changes	1291:1297	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	5	51	theme	anti-glycan	1194:1204	arg1	response					1213:1220	a heightened anti-glycan immune response	1181:1220	a heightened anti-glycan immune response	1181:1220	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	7	52	theme	cell	1473:1476	arg1	disease					1478:1484	sickle cell disease	1466:1484	sickle cell disease	1466:1484	Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets.
33666655	5	53	with	patients	1135:1142	arg1	disease					1161:1167	sickle cell disease	1149:1167	sickle cell disease	1149:1167	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	1	54	theme	pain	164:167	arg1	crises					169:174	pain crises	164:174	pain crises	164:174	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	7	55	theme	glycan	1435:1440	arg1	changes					1442:1448	glycan changes	1435:1448	glycan changes associated with sickle cell disease	1435:1484	Our data provide detailed insights into glycan changes associated with sickle cell disease and refer glycans as potential therapeutic targets.
33666655	6	56	theme	group	1377:1381	arg1	expression					1383:1392	ABO blood group expression	1367:1392	ABO blood group expression	1367:1392	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	6	57	theme	glycan	1246:1251	arg1	expression					1253:1262	glycan expression and plasma protein binding changes	1246:1297	expression	1253:1262	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	6	58	theme	further	1348:1354	arg1	changes					1356:1362	further changes	1348:1362	further changes in ABO blood group expression	1348:1392	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	2	59	theme	acid	291:294	arg1	levels					296:301	sialic acid levels	284:301	sialic acid levels	284:301	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	3	60	theme	healthy	756:762	arg1	individuals					764:774	healthy individuals	756:774	healthy individuals	756:774	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	5	61	theme	Lewis	1075:1079	arg1	A					1081:1081	Lewis A	1075:1081	Lewis A	1075:1081	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	3	62	theme	lectin	609:614	arg1	arrays					616:621	lectin arrays	609:621	lectin arrays	609:621	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	2	63	from	antibodies	511:520	arg1	disease					537:543	sickle cell disease	525:543	sickle cell disease	525:543	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	6	64	theme	Data	1223:1226	arg1	modeling					1228:1235	Data modeling	1223:1235	Data modeling	1223:1235	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	3	65	theme	cell	801:804	arg1	disease					806:812	sickle cell disease	794:812	sickle cell disease	794:812	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	5	66	located	observed	1111:1118	arg2	binding					1014:1020	Increased binding	1004:1020	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures	1004:1105	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	5	66	located	observed	1111:1118	arg1	plasma					1123:1128	plasma	1123:1128	plasma from patients with sickle cell disease	1123:1167	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	6	67	theme	sickle	1302:1307	arg1	disease					1314:1320	sickle cell disease	1302:1320	sickle cell disease	1302:1320	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	5	68	theme	sialyl	1060:1065	arg1	core					1067:1070	sialyl core 1	1060:1072	sialyl core 1	1060:1072	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	1	69	theme	genetic	127:133	arg1	disorder					135:142	an inherited genetic disorder	114:142	an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide	114:239	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	1	69	theme	genetic	127:133	arg1	disease					103:109	Sickle cell disease	91:109	Sickle cell disease	91:109	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	3	70	theme	cell	825:828	arg1	trait					830:834	sickle cell trait	818:834	sickle cell trait	818:834	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	0	71	theme	cell	77:80	arg1	disease					82:88	sickle cell disease	70:88	sickle cell disease	70:88	Characterization and statistical modeling of glycosylation changes in sickle cell disease.
33666655	2	72	from	changes	273:279	arg1	levels					296:301	sialic acid levels	284:301	sialic acid levels	284:301	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	2	73	theme	anti-glycan	499:509	arg1	antibodies					511:520	anti-glycan antibodies	499:520	anti-glycan antibodies	499:520	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	4	74	theme	blood	953:957	arg1	antigens					965:972	blood group antigens	953:972	blood group antigens	953:972	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	4	75	theme	blood	991:995	arg1	cells					997:1001	red blood cells	987:1001	red blood cells	987:1001	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	2	76	dep	changes	273:279	arg1	showed					347:352	showed	347:352	showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis	347:461	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	2	76	dep	changes	273:279	arg1	associated					303:312	associated	303:312	associated with red blood cell sickling	303:341	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	6	77	theme	blood	1371:1375	arg1	expression					1383:1392	ABO blood group expression	1367:1392	ABO blood group expression	1367:1392	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	2	78	theme	cell	532:535	arg1	disease					537:543	sickle cell disease	525:543	sickle cell disease	525:543	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	5	79	theme	Lewis	1088:1092	arg1	structures					1096:1105	Lewis Y structures	1088:1105	Lewis Y structures	1088:1105	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	2	80	theme	blood	372:376	arg1	cells					378:382	stressed red blood cells	359:382	stressed red blood cells	359:382	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	1	81	theme	Sickle	91:96	arg1	disorder					135:142	an inherited genetic disorder	114:142	an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide	114:239	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	1	81	theme	Sickle	91:96	arg1	disease					103:109	Sickle cell disease	91:109	Sickle cell disease	91:109	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	6	82	from	changes	1356:1362	arg1	expression					1383:1392	ABO blood group expression	1367:1392	ABO blood group expression	1367:1392	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	2	83	theme	stressed	359:366	arg1	cells					378:382	stressed red blood cells	359:382	stressed red blood cells	359:382	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	2	84	theme	mannose	424:430	arg1	structures					432:441	surface-exposed clustered terminal mannose structures	389:441	surface-exposed clustered terminal mannose structures mediating hemolysis	389:461	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	2	85	theme	clustered	405:413	arg1	structures					432:441	surface-exposed clustered terminal mannose structures	389:441	surface-exposed clustered terminal mannose structures mediating hemolysis	389:461	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	0	86	theme	glycosylation	45:57	arg1	Characterization					0:15	Characterization	0:15	Characterization	0:15	Characterization and statistical modeling of glycosylation changes in sickle cell disease.
33666655	0	86	theme	glycosylation	45:57	arg1	modeling					33:40	statistical modeling	21:40	statistical modeling	21:40	Characterization and statistical modeling of glycosylation changes in sickle cell disease.
33666655	5	87	theme	proteins	1025:1032	arg1	binding					1014:1020	Increased binding	1004:1020	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures	1004:1105	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	2	88	theme	detailed	468:475	arg1	structures					484:493	detailed glycan structures	468:493	detailed glycan structures	468:493	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	6	89	from	changes	1291:1297	arg1	disease					1314:1320	sickle cell disease	1302:1320	sickle cell disease	1302:1320	Data modeling affirmed glycan expression and plasma protein binding changes in sickle cell disease but additionally revealed further changes in ABO blood group expression.
33666655	5	90	theme	immunogenic	1037:1047	arg1	asialo					1049:1054	immunogenic asialo	1037:1054	immunogenic asialo	1037:1054	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	3	91	theme	blood	680:684	arg1	glycoproteins					691:703	red blood cell glycoproteins	676:703	red blood cell glycoproteins	676:703	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	4	92	theme	Lectin	837:842	arg1	arrays					844:849	Lectin arrays	837:849	Lectin arrays	837:849	Lectin arrays and mass spectrometry revealed an increase in α2,6 sialylation and a decrease in α2,3 sialylation and blood group antigens displayed on red blood cells.
33666655	2	93	theme	blood	323:327	arg1	cell					329:332	red blood cell	319:332	red blood cell sickling	319:341	Previous studies have revealed changes in sialic acid levels associated with red blood cell sickling and showed that stressed red blood cells bare surface-exposed clustered terminal mannose structures mediating hemolysis, but detailed glycan structures and anti-glycan antibodies in sickle cell disease remain understudied.
33666655	5	94	theme	sickle	1149:1154	arg1	disease					1161:1167	sickle cell disease	1149:1167	sickle cell disease	1149:1167	Increased binding of proteins to immunogenic asialo and sialyl core 1, Lewis A, and Lewis Y structures was observed in plasma from patients with sickle cell disease, suggesting a heightened anti-glycan immune response.
33666655	1	95	theme	13	213:214	arg1	million					216:222	million	216:222	million	216:222	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33666655	3	96	theme	glycan-binding	709:722	arg1	proteins					724:731	glycan-binding proteins	709:731	glycan-binding proteins	709:731	Here, we compiled results obtained through lectin arrays, glycan arrays, and mass spectrometry to interrogate red blood cell glycoproteins and glycan-binding proteins found in the plasma of healthy individuals and patients with sickle cell disease and sickle cell trait.
33666655	1	97	theme	people	224:229	arg1	worldwide					231:239	13 million people worldwide	213:239	13 million people worldwide	213:239	Sickle cell disease is an inherited genetic disorder that causes anemia, pain crises, organ infarction, and infections in 13 million people worldwide.
33305950	9	0	theme	quality	1573:1579	arg1	attributes					1581:1590	these mAb quality attributes	1563:1590	these mAb quality attributes	1563:1590	The method was deemed fit-for-purpose for assessment of these mAb quality attributes and involved fewer chemical preparation steps than the classical approaches that cleave glycans prior to making measurements.
33305950	3	1	from	mAbs	672:675	arg1	cleavage					654:661	glycan cleavage	647:661	glycan cleavage from the mAbs	647:675	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	2	2	from	changes	315:321	arg1	abundance					339:347	the relative abundance	326:347	the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation	326:430	Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation are known to change mAb properties and functions.
33305950	1	3	theme	complement-dependent	261:280	arg1	CDC					296:298	CDC	296:298	CDC	296:298	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	1	3	theme	complement-dependent	261:280	arg1	cytotoxicity					282:293	complement-dependent cytotoxicity	261:293	complement-dependent cytotoxicity (CDC)	261:299	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	7	4	theme	galactosylation	1360:1374	arg1	level					1316:1320	significantly lower level	1296:1320	significantly lower level of high mannose	1296:1336	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	4	theme	galactosylation	1360:1374	arg1	level					1351:1355	a higher level	1342:1355	a higher level of galactosylation	1342:1374	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	9	5	theme	fewer	1605:1609	arg1	steps					1632:1636	fewer chemical preparation steps	1605:1636	fewer chemical preparation steps	1605:1636	The method was deemed fit-for-purpose for assessment of these mAb quality attributes and involved fewer chemical preparation steps than the classical approaches that cleave glycans prior to making measurements.
33305950	7	6	theme	high	1325:1328	arg1	mannose					1330:1336	high mannose	1325:1336	high mannose	1325:1336	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	3	7	theme	based	519:523	arg1	procedure					536:544	a middle-down NMR spectroscopy based analytical procedure	488:544	a middle-down NMR spectroscopy based analytical procedure	488:544	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	3	8	dep	composition	572:582	arg1	the					568:570	the	568:570	the	568:570	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	9	9	theme	preparation	1620:1630	arg1	steps					1632:1636	fewer chemical preparation steps	1605:1636	fewer chemical preparation steps	1605:1636	The method was deemed fit-for-purpose for assessment of these mAb quality attributes and involved fewer chemical preparation steps than the classical approaches that cleave glycans prior to making measurements.
33305950	1	10	theme	plasma	185:190	arg1	clearance					192:200	monoclonal antibody (mAb) drug plasma clearance	154:200	monoclonal antibody (mAb) drug plasma clearance	154:200	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	6	11	theme	high	1117:1120	arg1	mannose					1122:1128	high mannose	1117:1128	high mannose (HM%)	1117:1134	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	6	11	theme	high	1117:1120	arg1	%					1133:1133	HM%	1131:1133	HM%	1131:1133	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	5	12	theme	C1/H1	834:838	arg1	resonances					840:849	the anomeric C1/H1 resonances	821:849	the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4)	821:910	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	12	theme	C1/H1	834:838	arg1	peaks					946:950	characteristic peaks	931:950	characteristic peaks for key glycan anomeric linkages and branching states	931:1004	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	9	13	theme	classical	1647:1655	arg1	approaches					1657:1666	the classical approaches	1643:1666	the classical approaches that cleave glycans prior to making measurements	1643:1715	The method was deemed fit-for-purpose for assessment of these mAb quality attributes and involved fewer chemical preparation steps than the classical approaches that cleave glycans prior to making measurements.
33305950	1	14	theme	cell	222:225	arg1	ADCC					250:253	ADCC	250:253	ADCC	250:253	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	1	14	theme	cell	222:225	arg1	cytotoxicity					236:247	antibody-dependent cell mediated cytotoxicity	203:247	antibody-dependent cell mediated cytotoxicity (ADCC)	203:254	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	6	15	theme	galactosylation	1157:1171	arg1	glycans					1077:1083	minor glycans	1071:1083	minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%)	1071:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	4	16	theme	distinct	716:723	arg1	patterns					725:732	distinct patterns	716:732	distinct patterns that could be used to profile and differentiate mAb glycan compositions	716:804	The anomeric 2D 1H-13C spectra showed distinct patterns that could be used to profile and differentiate mAb glycan compositions.
33305950	6	17	dep	galactosylation	1157:1171	arg1	%					1180:1180	Gal1-3%	1174:1180	Gal1-3%	1174:1180	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	6	17	dep	galactosylation	1157:1171	arg1	%					1192:1192	Gal1-6%	1186:1192	Gal1-6%	1186:1192	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	6	18	theme	branch	1141:1146	arg1	galactosylation					1157:1171	branch specific galactosylation	1141:1171	branch specific galactosylation (Gal1-3% and Gal1-6%)	1141:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	0	19	theme	Middle-Down	65:75	arg1	Spectroscopy					81:92	Middle-Down NMR Spectroscopy	65:92	Middle-Down NMR Spectroscopy	65:92	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.
33305950	3	20	theme	glycans	601:607	arg1	structure					588:596	structure	588:596	structure	588:596	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	3	20	theme	glycans	601:607	arg1	composition					572:582	composition	572:582	composition	572:582	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	5	21	from	N-acetylglucosamine	856:874	arg1	resonances					840:849	the anomeric C1/H1 resonances	821:849	the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4)	821:910	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	21	from	N-acetylglucosamine	856:874	arg1	peaks					946:950	characteristic peaks	931:950	characteristic peaks for key glycan anomeric linkages and branching states	931:1004	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	1	22	theme	monoclonal	154:163	arg1	mAb					175:177	mAb	175:177	mAb	175:177	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	1	22	theme	monoclonal	154:163	arg1	antibody					165:172	monoclonal antibody	154:172	monoclonal antibody (mAb) drug plasma clearance	154:200	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	4	23	theme	2D	691:692	arg1	spectra					701:707	The anomeric 2D 1H-13C spectra	678:707	The anomeric 2D 1H-13C spectra	678:707	The anomeric 2D 1H-13C spectra showed distinct patterns that could be used to profile and differentiate mAb glycan compositions.
33305950	6	24	used	utilized	1022:1029	arg2	They					1007:1010	They	1007:1010	They	1007:1010	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	8	25	theme	2D-NMR	1406:1411	arg1	measurements					1413:1424	the 2D-NMR measurements	1402:1424	the 2D-NMR measurements	1402:1424	Overall, the 2D-NMR measurements provided functionally relevant mAb glycan composition and structure information.
33305950	5	26	theme	key	956:958	arg1	linkages					976:983	key glycan anomeric linkages	956:983	key glycan anomeric linkages	956:983	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	27	theme	anomeric	967:974	arg1	linkages					976:983	key glycan anomeric linkages	956:983	key glycan anomeric linkages	956:983	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	8	28	theme	relevant	1448:1455	arg1	composition					1468:1478	functionally relevant mAb glycan composition and structure information	1435:1504	composition	1468:1478	Overall, the 2D-NMR measurements provided functionally relevant mAb glycan composition and structure information.
33305950	0	29	theme	Minor	0:4	arg1	Mapping					15:21	Minor N-Glycan Mapping	0:21	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics	0:57	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.
33305950	1	30	theme	N-glycosylation	99:113	arg1	pattern					115:121	The N-glycosylation pattern	95:121	The N-glycosylation pattern of Asn-297	95:132	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	6	31	theme	relative	1049:1056	arg1	abundance					1058:1066	the relative abundance	1045:1066	the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%)	1045:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	8	32	theme	glycan	1461:1466	arg1	composition					1468:1478	functionally relevant mAb glycan composition and structure information	1435:1504	composition	1468:1478	Overall, the 2D-NMR measurements provided functionally relevant mAb glycan composition and structure information.
33305950	3	33	from	composition	572:582	arg1	trastuzumab					627:637	trastuzumab	627:637	trastuzumab	627:637	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	3	33	from	composition	572:582	arg1	adalimumab					612:621	adalimumab	612:621	adalimumab	612:621	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	3	34	theme	glycan	647:652	arg1	cleavage					654:661	glycan cleavage	647:661	glycan cleavage from the mAbs	647:675	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	3	35	from	structure	588:596	arg1	trastuzumab					627:637	trastuzumab	627:637	trastuzumab	627:637	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	3	35	from	structure	588:596	arg1	adalimumab					612:621	adalimumab	612:621	adalimumab	612:621	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	0	36	theme	Monoclonal	26:35	arg1	Therapeutics					46:57	Monoclonal Antibody Therapeutics	26:57	Monoclonal Antibody Therapeutics	26:57	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.
33305950	5	37	dep	N-acetylglucosamine	856:874	arg1	-5					889:890	-5	889:890	-5	889:890	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	37	dep	N-acetylglucosamine	856:874	arg1	GlcNAc2					877:883	GlcNAc2	877:883	GlcNAc2	877:883	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	2	38	theme	relative	330:337	arg1	abundance					339:347	the relative abundance	326:347	the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation	326:430	Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation are known to change mAb properties and functions.
33305950	0	39	theme	Therapeutics	46:57	arg1	Mapping					15:21	Minor N-Glycan Mapping	0:21	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics	0:57	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.
33305950	7	40	theme	aFuc	1215:1218	arg1	similar					1241:1247	similar	1241:1247	similar	1241:1247	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	40	theme	aFuc	1215:1218	arg1	value					1221:1225	The obtained total aFuc% value	1196:1225	The obtained total aFuc% value of 11-12%	1196:1235	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	4	41	theme	mAb	782:784	arg1	compositions					793:804	mAb glycan compositions	782:804	mAb glycan compositions	782:804	The anomeric 2D 1H-13C spectra showed distinct patterns that could be used to profile and differentiate mAb glycan compositions.
33305950	1	42	theme	mediated	227:234	arg1	ADCC					250:253	ADCC	250:253	ADCC	250:253	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	1	42	theme	mediated	227:234	arg1	cytotoxicity					236:247	antibody-dependent cell mediated cytotoxicity	203:247	antibody-dependent cell mediated cytotoxicity (ADCC)	203:254	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	6	43	theme	HM	1131:1132	arg1	mannose					1122:1128	high mannose	1117:1128	high mannose (HM%)	1117:1134	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	6	43	theme	HM	1131:1132	arg1	%					1133:1133	HM%	1131:1133	HM%	1131:1133	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	7	44	theme	obtained	1200:1207	arg1	similar					1241:1247	similar	1241:1247	similar	1241:1247	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	44	theme	obtained	1200:1207	arg1	value					1221:1225	The obtained total aFuc% value	1196:1225	The obtained total aFuc% value of 11-12%	1196:1235	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	3	45	theme	middle-down	490:500	arg1	spectroscopy					506:517	a middle-down NMR spectroscopy	488:517	a middle-down NMR spectroscopy based analytical procedure	488:544	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	9	46	theme	mAb	1569:1571	arg1	attributes					1581:1590	these mAb quality attributes	1563:1590	these mAb quality attributes	1563:1590	The method was deemed fit-for-purpose for assessment of these mAb quality attributes and involved fewer chemical preparation steps than the classical approaches that cleave glycans prior to making measurements.
33305950	6	47	theme	total	1088:1092	arg1	afucosylation					1094:1106	total afucosylation	1088:1106	total afucosylation (aFuc%)	1088:1114	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	6	47	theme	total	1088:1092	arg1	%					1113:1113	aFuc%	1109:1113	aFuc%	1109:1113	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	1	48	contain	have	138:141	arg2	impacts					143:149	impacts	143:149	impacts	143:149	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	1	48	contain	have	138:141	arg1	pattern					115:121	The N-glycosylation pattern	95:121	The N-glycosylation pattern of Asn-297	95:132	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	9	49	theme	attributes	1581:1590	arg1	assessment					1549:1558	assessment	1549:1558	assessment of these mAb quality attributes	1549:1590	The method was deemed fit-for-purpose for assessment of these mAb quality attributes and involved fewer chemical preparation steps than the classical approaches that cleave glycans prior to making measurements.
33305950	6	50	theme	glycans	1077:1083	arg1	abundance					1058:1066	the relative abundance	1045:1066	the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%)	1045:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	3	51	theme	analytical	525:534	arg1	procedure					536:544	a middle-down NMR spectroscopy based analytical procedure	488:544	a middle-down NMR spectroscopy based analytical procedure	488:544	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	7	52	contain	had	1292:1294	arg1	trastuzumab					1280:1290	trastuzumab	1280:1290	trastuzumab	1280:1290	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	52	contain	had	1292:1294	arg2	level					1351:1355	a higher level	1342:1355	a higher level of galactosylation	1342:1374	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	52	contain	had	1292:1294	arg2	level					1316:1320	significantly lower level	1296:1320	significantly lower level of high mannose	1296:1336	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	3	53	theme	spectroscopy	506:517	arg1	procedure					536:544	a middle-down NMR spectroscopy based analytical procedure	488:544	a middle-down NMR spectroscopy based analytical procedure	488:544	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33305950	7	54	theme	higher	1344:1349	arg1	level					1351:1355	a higher level	1342:1355	a higher level of galactosylation	1342:1374	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	9	55	theme	chemical	1611:1618	arg1	steps					1632:1636	fewer chemical preparation steps	1605:1636	fewer chemical preparation steps	1605:1636	The method was deemed fit-for-purpose for assessment of these mAb quality attributes and involved fewer chemical preparation steps than the classical approaches that cleave glycans prior to making measurements.
33305950	7	56	theme	mannose	1330:1336	arg1	level					1316:1320	significantly lower level	1296:1320	significantly lower level of high mannose	1296:1336	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	56	theme	mannose	1330:1336	arg1	level					1351:1355	a higher level	1342:1355	a higher level of galactosylation	1342:1374	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	1	57	theme	drug	180:183	arg1	clearance					192:200	monoclonal antibody (mAb) drug plasma clearance	154:200	monoclonal antibody (mAb) drug plasma clearance	154:200	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	6	58	theme	mannose	1122:1128	arg1	glycans					1077:1083	minor glycans	1071:1083	minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%)	1071:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	5	59	theme	anomeric	825:832	arg1	resonances					840:849	the anomeric C1/H1 resonances	821:849	the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4)	821:910	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	59	theme	anomeric	825:832	arg1	peaks					946:950	characteristic peaks	931:950	characteristic peaks for key glycan anomeric linkages and branching states	931:1004	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	7	60	theme	lower	1310:1314	arg1	level					1316:1320	significantly lower level	1296:1320	significantly lower level of high mannose	1296:1336	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	1	61	theme	antibody-dependent	203:220	arg1	ADCC					250:253	ADCC	250:253	ADCC	250:253	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	1	61	theme	antibody-dependent	203:220	arg1	cytotoxicity					236:247	antibody-dependent cell mediated cytotoxicity	203:247	antibody-dependent cell mediated cytotoxicity (ADCC)	203:254	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	1	62	theme	Asn-297	126:132	arg1	pattern					115:121	The N-glycosylation pattern	95:121	The N-glycosylation pattern of Asn-297	95:132	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	4	63	theme	1H-13C	694:699	arg1	spectra					701:707	The anomeric 2D 1H-13C spectra	678:707	The anomeric 2D 1H-13C spectra	678:707	The anomeric 2D 1H-13C spectra showed distinct patterns that could be used to profile and differentiate mAb glycan compositions.
33305950	6	64	theme	specific	1148:1155	arg1	galactosylation					1157:1171	branch specific galactosylation	1141:1171	branch specific galactosylation (Gal1-3% and Gal1-6%)	1141:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	0	65	theme	NMR	77:79	arg1	Spectroscopy					81:92	Middle-Down NMR Spectroscopy	65:92	Middle-Down NMR Spectroscopy	65:92	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.
33305950	1	66	theme	antibody	165:172	arg1	clearance					192:200	monoclonal antibody (mAb) drug plasma clearance	154:200	monoclonal antibody (mAb) drug plasma clearance	154:200	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	4	67	theme	anomeric	682:689	arg1	spectra					701:707	The anomeric 2D 1H-13C spectra	678:707	The anomeric 2D 1H-13C spectra	678:707	The anomeric 2D 1H-13C spectra showed distinct patterns that could be used to profile and differentiate mAb glycan compositions.
33305950	1	68	gly	N-glycosylation	99:113	arg1	Asn-297					126:132	Asn-297	126:132	Asn-297	126:132	The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
33305950	5	69	from	mannose	897:903	arg1	resonances					840:849	the anomeric C1/H1 resonances	821:849	the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4)	821:910	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	69	from	mannose	897:903	arg1	peaks					946:950	characteristic peaks	931:950	characteristic peaks for key glycan anomeric linkages and branching states	931:1004	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	70	theme	glycan	960:965	arg1	linkages					976:983	key glycan anomeric linkages	956:983	key glycan anomeric linkages	956:983	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	6	71	theme	minor	1071:1075	arg1	glycans					1077:1083	minor glycans	1071:1083	minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%)	1071:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	8	72	theme	mAb	1457:1459	arg1	composition					1468:1478	functionally relevant mAb glycan composition and structure information	1435:1504	composition	1468:1478	Overall, the 2D-NMR measurements provided functionally relevant mAb glycan composition and structure information.
33305950	0	73	theme	N-Glycan	6:13	arg1	Mapping					15:21	Minor N-Glycan Mapping	0:21	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics	0:57	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.
33305950	7	74	theme	%	1235:1235	arg1	similar					1241:1247	similar	1241:1247	similar	1241:1247	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	74	theme	%	1235:1235	arg1	value					1221:1225	The obtained total aFuc% value	1196:1225	The obtained total aFuc% value of 11-12%	1196:1235	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	2	75	theme	glycans	366:372	arg1	abundance					339:347	the relative abundance	326:347	the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation	326:430	Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation are known to change mAb properties and functions.
33305950	5	76	theme	characteristic	931:944	arg1	resonances					840:849	the anomeric C1/H1 resonances	821:849	the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4)	821:910	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	5	76	theme	characteristic	931:944	arg1	peaks					946:950	characteristic peaks	931:950	characteristic peaks for key glycan anomeric linkages and branching states	931:1004	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	8	77	theme	structure	1484:1492	arg1	information					1494:1504	functionally relevant mAb glycan composition and structure information	1435:1504	information	1494:1504	Overall, the 2D-NMR measurements provided functionally relevant mAb glycan composition and structure information.
33305950	2	78	theme	minor	360:364	arg1	glycans					366:372	certain minor glycans	352:372	certain minor glycans	352:372	Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation are known to change mAb properties and functions.
33305950	0	79	theme	Antibody	37:44	arg1	Therapeutics					46:57	Monoclonal Antibody Therapeutics	26:57	Monoclonal Antibody Therapeutics	26:57	Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.
33305950	7	80	theme	%	1219:1219	arg1	similar					1241:1247	similar	1241:1247	similar	1241:1247	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	80	theme	%	1219:1219	arg1	value					1221:1225	The obtained total aFuc% value	1196:1225	The obtained total aFuc% value of 11-12%	1196:1235	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	2	81	theme	mAb	452:454	arg1	properties					456:465	mAb properties	452:465	mAb properties	452:465	Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation are known to change mAb properties and functions.
33305950	2	82	dep	afucosylation	384:396	arg1	the					380:382	the	380:382	the	380:382	Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation are known to change mAb properties and functions.
33305950	7	83	theme	total	1209:1213	arg1	similar					1241:1247	similar	1241:1247	similar	1241:1247	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	7	83	theme	total	1209:1213	arg1	value					1221:1225	The obtained total aFuc% value	1196:1225	The obtained total aFuc% value of 11-12%	1196:1235	The obtained total aFuc% value of 11-12% was similar between the two mAbs; however, trastuzumab had significantly lower level of high mannose and a higher level of galactosylation than adalimumab.
33305950	2	84	theme	certain	352:358	arg1	glycans					366:372	certain minor glycans	352:372	certain minor glycans	352:372	Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, or galactosylation are known to change mAb properties and functions.
33305950	4	85	used	used	748:751	arg2	patterns					725:732	distinct patterns	716:732	distinct patterns that could be used to profile and differentiate mAb glycan compositions	716:804	The anomeric 2D 1H-13C spectra showed distinct patterns that could be used to profile and differentiate mAb glycan compositions.
33305950	5	86	theme	branching	989:997	arg1	states					999:1004	branching states	989:1004	branching states	989:1004	Specifically, the anomeric C1/H1 resonances from N-acetylglucosamine (GlcNAc2 and -5) and mannose (Man4) were identified as characteristic peaks for key glycan anomeric linkages and branching states.
33305950	6	87	theme	afucosylation	1094:1106	arg1	glycans					1077:1083	minor glycans	1071:1083	minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%)	1071:1193	They were also utilized for measuring the relative abundance of minor glycans of total afucosylation (aFuc%), high mannose (HM%), and branch specific galactosylation (Gal1-3% and Gal1-6%).
33305950	4	88	theme	glycan	786:791	arg1	compositions					793:804	mAb glycan compositions	782:804	mAb glycan compositions	782:804	The anomeric 2D 1H-13C spectra showed distinct patterns that could be used to profile and differentiate mAb glycan compositions.
33305950	3	89	theme	NMR	502:504	arg1	spectroscopy					506:517	a middle-down NMR spectroscopy	488:517	a middle-down NMR spectroscopy based analytical procedure	488:544	Here, a middle-down NMR spectroscopy based analytical procedure was applied to assess the composition and structure of glycans on adalimumab and trastuzumab without glycan cleavage from the mAbs.
33197804	3	0	attach	derived	439:445	arg2	mucins					432:437	METHODS SMG mucins	420:437	METHODS SMG mucins derived from mice of each age	420:467	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	3	0	attach	derived	439:445	arg1	mice					452:455	mice	452:455	mice of each age	452:467	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	5	1	theme	glycan	715:720	arg1	analysis					722:729	glycan analysis	715:729	glycan analysis	715:729	The SMME membranes stained with AB were subjected to densitometric analysis and glycan analysis.
33197804	9	2	theme	major	1206:1210	arg1	glycans					1212:1218	major glycans	1206:1218	major glycans	1206:1218	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	7	3	theme	age-specific	901:912	arg1	mucin					914:918	age-specific mucin	901:918	age-specific mucin	901:918	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	3	4	theme	age	465:467	arg1	mice					452:455	mice	452:455	mice of each age	452:467	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	9	5	contain	had	1185:1187	arg2	mass					1198:1201	the same mass	1189:1201	the same mass of major glycans but different structures	1189:1243	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	9	5	contain	had	1185:1187	arg1	mucin					1130:1134	A mucin	1128:1134	A mucin expressed throughout life and age-specific mucin	1128:1183	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	0	6	from	Alteration	0:9	arg1	gland					42:46	the submandibular gland	24:46	the submandibular gland during aging in mice	24:67	Alteration of mucins in the submandibular gland during aging in mice.
33197804	6	7	theme	O-glycan	759:766	arg1	structures					745:754	The detailed structures	732:754	The detailed structures of O-glycan	732:766	The detailed structures of O-glycan were investigated by tandem mass spectrometry (MS/MS).
33197804	3	8	theme	molecular	500:508	arg1	SMME					534:537	SMME	534:537	SMME	534:537	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	3	8	theme	molecular	500:508	arg1	electrophoresis					517:531	molecular matrix electrophoresis	500:531	supported molecular matrix electrophoresis (SMME)	490:538	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	7	9	theme	youth-specific	921:934	arg1	mucin					936:940	youth-specific mucin	921:940	youth-specific mucin	921:940	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	1	10	theme	salivary	149:156	arg1	glands					158:163	the salivary glands	145:163	the salivary glands	145:163	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	11	11	theme	process	1639:1645	arg1	period					1619:1624	the period	1615:1624	the period of the aging process	1615:1645	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	3	12	theme	matrix	510:515	arg1	SMME					534:537	SMME	534:537	SMME	534:537	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	3	12	theme	matrix	510:515	arg1	electrophoresis					517:531	molecular matrix electrophoresis	500:531	supported molecular matrix electrophoresis (SMME)	490:538	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	11	13	theme	secretory	1497:1505	arg1	mucins					1507:1512	three secretory mucins	1491:1512	three secretory mucins with different glycan profiles in the SMG of mice	1491:1562	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	0	14	from	gland	42:46	arg1	mice					64:67	mice	64:67	mice	64:67	Alteration of mucins in the submandibular gland during aging in mice.
33197804	12	15	theme	mucin	1684:1688	arg1	species					1673:1679	glycan species	1666:1679	glycan species of mucin expressed throughout life	1666:1714	The proportion of glycan species of mucin expressed throughout life also changes during the aging process.
33197804	2	16	theme	submandibular	368:380	arg1	SMG					389:391	SMG	389:391	SMG	389:391	This study aimed to characterize the changes in the mucins produced in submandibular gland (SMG) during the aging process.
33197804	2	16	theme	submandibular	368:380	arg1	gland					382:386	submandibular gland	368:386	submandibular gland (SMG)	368:392	This study aimed to characterize the changes in the mucins produced in submandibular gland (SMG) during the aging process.
33197804	9	17	theme	structures	1234:1243	arg1	mass					1198:1201	the same mass	1189:1201	the same mass of major glycans but different structures	1189:1243	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	2	18	from	changes	334:340	arg1	mucins					349:354	the mucins	345:354	the mucins produced in submandibular gland (SMG) during the aging process	345:417	This study aimed to characterize the changes in the mucins produced in submandibular gland (SMG) during the aging process.
33197804	3	19	theme	supported	490:498	arg1	SMME					534:537	SMME	534:537	SMME	534:537	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	3	19	theme	supported	490:498	arg1	electrophoresis					517:531	molecular matrix electrophoresis	500:531	supported molecular matrix electrophoresis (SMME)	490:538	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	10	20	theme	sialoglycans	1456:1467	arg1	proportion					1442:1451	the proportion	1438:1451	the proportion of sialoglycans	1438:1467	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	7	21	theme	glycan	884:889	arg1	profiles					891:898	different glycan profiles	874:898	different glycan profiles	874:898	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	1	22	theme	OBJECTIVE	70:78	arg1	Mucins					80:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	22	theme	OBJECTIVE	70:78	arg1	glycoproteins					110:122	large glycosylated glycoproteins	91:122	large glycosylated glycoproteins that are produced in the salivary glands	91:163	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	9	23	theme	different	1224:1232	arg1	structures					1234:1243	different structures	1224:1243	different structures	1224:1243	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	2	24	theme	aging	405:409	arg1	process					411:417	the aging process	401:417	the aging process	401:417	This study aimed to characterize the changes in the mucins produced in submandibular gland (SMG) during the aging process.
33197804	7	25	with	mucins	862:867	arg1	mucin					936:940	youth-specific mucin	921:940	youth-specific mucin	921:940	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	7	25	with	mucins	862:867	arg1	mucin					949:953	a mucin	947:953	a mucin expressed throughout life	947:979	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	7	25	with	mucins	862:867	arg1	profiles					891:898	different glycan profiles	874:898	different glycan profiles	874:898	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	7	25	with	mucins	862:867	arg1	mucin					914:918	age-specific mucin	901:918	age-specific mucin	901:918	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	7	26	theme	mucins	1019:1024	arg1	patterns					1001:1008	the expression patterns	986:1008	the expression patterns of these mucins	986:1024	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	12	27	theme	glycan	1666:1671	arg1	species					1673:1679	glycan species	1666:1679	glycan species of mucin expressed throughout life	1666:1714	The proportion of glycan species of mucin expressed throughout life also changes during the aging process.
33197804	8	28	located	detected	1092:1099	arg1	months					1113:1118	about 12 months	1104:1118	about 12 months of age	1104:1125	Additionally, age-specific mucin began to be detected at about 12 months of age.
33197804	8	28	located	detected	1092:1099	arg2	mucin					1074:1078	age-specific mucin	1061:1078	age-specific mucin	1061:1078	Additionally, age-specific mucin began to be detected at about 12 months of age.
33197804	11	29	theme	mice	1559:1562	arg1	SMG					1552:1554	the SMG	1548:1554	the SMG of mice	1548:1562	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	8	30	theme	age	1123:1125	arg1	months					1113:1118	about 12 months	1104:1118	about 12 months of age	1104:1125	Additionally, age-specific mucin began to be detected at about 12 months of age.
33197804	1	31	theme	accompanying	253:264	arg1	deterioration					266:278	the accompanying deterioration	249:278	the accompanying deterioration of oral hygiene	249:294	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	32	gly	glycoproteins	110:122	arg1	Mucins					80:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	32	gly	glycoproteins	110:122	arg1	glycoproteins					110:122	large glycosylated glycoproteins	91:122	large glycosylated glycoproteins that are produced in the salivary glands	91:163	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	7	33	dep	SMG	835:837	arg1	RESULTS					823:829	RESULTS	823:829	RESULTS	823:829	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	3	34	theme	SMG	428:430	arg1	mucins					432:437	METHODS SMG mucins	420:437	METHODS SMG mucins derived from mice of each age	420:467	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	0	35	theme	mucins	14:19	arg1	Alteration					0:9	Alteration	0:9	Alteration of mucins in the submandibular gland during aging in mice.	0:68	Alteration of mucins in the submandibular gland during aging in mice.
33197804	1	36	gly	glycosylated	97:108	arg1	Mucins					80:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	36	gly	glycosylated	97:108	arg1	glycoproteins					110:122	large glycosylated glycoproteins	91:122	large glycosylated glycoproteins that are produced in the salivary glands	91:163	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	37	theme	large	91:95	arg1	Mucins					80:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	37	theme	large	91:95	arg1	glycoproteins					110:122	large glycosylated glycoproteins	91:122	large glycosylated glycoproteins that are produced in the salivary glands	91:163	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	10	38	theme	aging	1343:1347	arg1	process					1349:1355	the aging process	1339:1355	the aging process	1339:1355	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	0	39	theme	submandibular	28:40	arg1	gland					42:46	the submandibular gland	24:46	the submandibular gland during aging in mice	24:67	Alteration of mucins in the submandibular gland during aging in mice.
33197804	11	40	with	mucins	1507:1512	arg1	profiles					1536:1543	different glycan profiles	1519:1543	different glycan profiles in the SMG of mice	1519:1562	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	10	41	theme	fucosylated	1405:1415	arg1	glycans					1417:1423	fucosylated glycans	1405:1423	fucosylated glycans	1405:1423	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	10	42	gly	fucosylated	1405:1415	arg1	glycans					1417:1423	fucosylated glycans	1405:1423	fucosylated glycans	1405:1423	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	1	43	theme	oral	283:286	arg1	hygiene					288:294	oral hygiene	283:294	oral hygiene	283:294	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	7	44	theme	expression	990:999	arg1	patterns					1001:1008	the expression patterns	986:1008	the expression patterns of these mucins	986:1024	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	12	45	theme	aging	1740:1744	arg1	process					1746:1752	the aging process	1736:1752	the aging process	1736:1752	The proportion of glycan species of mucin expressed throughout life also changes during the aging process.
33197804	11	46	theme	glycan	1529:1534	arg1	profiles					1536:1543	different glycan profiles	1519:1543	different glycan profiles in the SMG of mice	1519:1562	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	3	47	theme	METHODS	420:426	arg1	mucins					432:437	METHODS SMG mucins	420:437	METHODS SMG mucins derived from mice of each age	420:467	METHODS SMG mucins derived from mice of each age were separated using supported molecular matrix electrophoresis (SMME).
33197804	1	48	theme	hygiene	288:294	arg1	deterioration					266:278	the accompanying deterioration	249:278	the accompanying deterioration of oral hygiene	249:294	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	48	theme	hygiene	288:294	arg1	aging					239:243	aging	239:243	aging	239:243	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	9	49	theme	age-specific	1166:1177	arg1	mucin					1179:1183	age-specific mucin	1166:1183	age-specific mucin	1166:1183	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	11	50	theme	expression	1575:1584	arg1	patterns					1586:1593	their expression patterns	1569:1593	their expression patterns	1569:1593	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	1	51	theme	glycosylated	97:108	arg1	Mucins					80:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins	70:85	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	1	51	theme	glycosylated	97:108	arg1	glycoproteins					110:122	large glycosylated glycoproteins	91:122	large glycosylated glycoproteins that are produced in the salivary glands	91:163	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33197804	9	52	theme	glycans	1212:1218	arg1	mass					1198:1201	the same mass	1189:1201	the same mass of major glycans but different structures	1189:1243	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	5	53	theme	SMME	639:642	arg1	membranes					644:652	The SMME membranes	635:652	The SMME membranes stained with AB	635:668	The SMME membranes stained with AB were subjected to densitometric analysis and glycan analysis.
33197804	6	54	theme	mass	796:799	arg1	MS/MS					815:819	MS/MS	815:819	MS/MS	815:819	The detailed structures of O-glycan were investigated by tandem mass spectrometry (MS/MS).
33197804	6	54	theme	mass	796:799	arg1	spectrometry					801:812	tandem mass spectrometry	789:812	tandem mass spectrometry (MS/MS)	789:820	The detailed structures of O-glycan were investigated by tandem mass spectrometry (MS/MS).
33197804	7	55	theme	different	874:882	arg1	profiles					891:898	different glycan profiles	874:898	different glycan profiles	874:898	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	6	56	theme	tandem	789:794	arg1	MS/MS					815:819	MS/MS	815:819	MS/MS	815:819	The detailed structures of O-glycan were investigated by tandem mass spectrometry (MS/MS).
33197804	6	56	theme	tandem	789:794	arg1	spectrometry					801:812	tandem mass spectrometry	789:812	tandem mass spectrometry (MS/MS)	789:820	The detailed structures of O-glycan were investigated by tandem mass spectrometry (MS/MS).
33197804	11	57	theme	aging	1633:1637	arg1	process					1639:1645	the aging process	1629:1645	the aging process	1629:1645	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	6	58	theme	detailed	736:743	arg1	structures					745:754	The detailed structures	732:754	The detailed structures of O-glycan	732:766	The detailed structures of O-glycan were investigated by tandem mass spectrometry (MS/MS).
33197804	11	59	theme	different	1519:1527	arg1	profiles					1536:1543	different glycan profiles	1519:1543	different glycan profiles in the SMG of mice	1519:1562	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	10	60	theme	species	1290:1296	arg1	proportion					1263:1272	the proportion	1259:1272	the proportion of mucin glycan species expressed throughout life	1259:1322	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	11	61	dep	CONCLUSION	1470:1479	arg1	are					1487:1489	are	1487:1489	are three secretory mucins with different glycan profiles in the SMG of mice	1487:1562	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	5	62	theme	densitometric	688:700	arg1	analysis					702:709	densitometric analysis	688:709	densitometric analysis	688:709	The SMME membranes stained with AB were subjected to densitometric analysis and glycan analysis.
33197804	9	63	theme	same	1193:1196	arg1	mass					1198:1201	the same mass	1189:1201	the same mass of major glycans but different structures	1189:1243	A mucin expressed throughout life and age-specific mucin had the same mass of major glycans but different structures.
33197804	12	64	theme	species	1673:1679	arg1	proportion					1652:1661	The proportion	1648:1661	The proportion of glycan species of mucin expressed throughout life	1648:1714	The proportion of glycan species of mucin expressed throughout life also changes during the aging process.
33197804	10	65	theme	glycan	1283:1288	arg1	species					1290:1296	mucin glycan species	1277:1296	mucin glycan species expressed throughout life	1277:1322	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	7	66	theme	mice	842:845	arg1	SMG					835:837	The SMG	831:837	The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life	831:979	RESULTS The SMG of mice secreted three mucins with different glycan profiles: age-specific mucin, youth-specific mucin, and a mucin expressed throughout life, and the expression patterns of these mucins change during aging.
33197804	10	67	theme	glycans	1417:1423	arg1	proportion					1391:1400	the proportion	1387:1400	the proportion of fucosylated glycans	1387:1423	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	8	68	theme	age-specific	1061:1072	arg1	mucin					1074:1078	age-specific mucin	1061:1078	age-specific mucin	1061:1078	Additionally, age-specific mucin began to be detected at about 12 months of age.
33197804	10	69	theme	mucin	1277:1281	arg1	species					1290:1296	mucin glycan species	1277:1296	mucin glycan species expressed throughout life	1277:1322	Furthermore, the proportion of mucin glycan species expressed throughout life changed during the aging process, and aging tended to decrease the proportion of fucosylated glycans and increase the proportion of sialoglycans.
33197804	4	70	theme	MAL-II	620:625	arg1	lectin					627:632	MAL-II lectin	620:632	MAL-II lectin	620:632	Subsequently, the membranes were stained with Alcian blue (AB) or blotted with MAL-II lectin.
33197804	11	71	from	profiles	1536:1543	arg1	SMG					1552:1554	the SMG	1548:1554	the SMG of mice	1548:1562	CONCLUSION There are three secretory mucins with different glycan profiles in the SMG of mice, and their expression patterns change according to the period of the aging process.
33197804	1	72	theme	xerostomia	221:230	arg1	development					206:216	the development	202:216	the development of xerostomia due to aging and the accompanying deterioration of oral hygiene	202:294	OBJECTIVE Mucins are large glycosylated glycoproteins that are produced in the salivary glands, and their changes may contribute to the development of xerostomia due to aging and the accompanying deterioration of oral hygiene.
33730547	0	0	from	mapping	7:13	arg1	cells					58:62	human-derived cells	44:62	human-derived cells	44:62	Global mapping of glycosylation pathways in human-derived cells.
33730547	5	1	theme	global	589:594	arg1	pathways					613:620	global glycan metabolic pathways	589:620	global glycan metabolic pathways	589:620	Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses.
33730547	1	2	theme	broad	148:152	arg1	range					154:158	a broad range	146:158	a broad range of biological phenomena	146:182	Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena.
33730547	3	3	theme	glycosylation	337:349	arg1	tool					359:362	a comprehensive glycosylation mapping tool	321:362	a comprehensive glycosylation mapping tool	321:362	Here, we developed a comprehensive glycosylation mapping tool, termed GlycoMaple, to visualize and estimate glycan structures based on gene expression.
33730547	5	4	theme	glycan	596:601	arg1	pathways					613:620	global glycan metabolic pathways	589:620	global glycan metabolic pathways	589:620	Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses.
33730547	7	5	theme	glycan	869:874	arg1	structures					876:885	the glycan structures	865:885	the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues	865:947	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	3	6	theme	mapping	351:357	arg1	tool					359:362	a comprehensive glycosylation mapping tool	321:362	a comprehensive glycosylation mapping tool	321:362	Here, we developed a comprehensive glycosylation mapping tool, termed GlycoMaple, to visualize and estimate glycan structures based on gene expression.
33730547	8	7	theme	systematic	1017:1026	arg1	approach					1028:1035	Our systematic approach	1013:1035	Our systematic approach	1013:1035	Our systematic approach can accelerate glycan analyses and engineering in mammalian cells.
33730547	5	8	theme	metabolic	603:611	arg1	pathways					613:620	global glycan metabolic pathways	589:620	global glycan metabolic pathways	589:620	Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses.
33730547	2	9	theme	cell	264:267	arg1	types					269:273	tissue or cell types	254:273	types	269:273	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	6	10	from	effects	809:815	arg1	structures					844:853	glycan structures	837:853	glycan structures	837:853	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	7	11	theme	colon	929:933	arg1	tissues					941:947	primary colon tumor tissues	921:947	primary colon tumor tissues	921:947	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	3	12	theme	comprehensive	323:335	arg1	tool					359:362	a comprehensive glycosylation mapping tool	321:362	a comprehensive glycosylation mapping tool	321:362	Here, we developed a comprehensive glycosylation mapping tool, termed GlycoMaple, to visualize and estimate glycan structures based on gene expression.
33730547	7	13	theme	available	992:1000	arg1	databases					1002:1010	publicly available databases	983:1010	publicly available databases	983:1010	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	5	14	theme	genes	566:570	arg1	profiles					548:555	Expression profiles	537:555	Expression profiles of these genes	537:570	Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses.
33730547	2	15	theme	tissue	254:259	arg1	types					269:273	tissue or cell types	254:273	types	269:273	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	7	16	theme	primary	921:927	arg1	tissues					941:947	primary colon tumor tissues	921:947	primary colon tumor tissues	921:947	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	5	17	theme	glycan	633:638	arg1	structures					640:649	glycan structures	633:649	glycan structures	633:649	Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses.
33730547	0	18	link	human-derived	44:56	arg1	cells					58:62	human-derived cells	44:62	human-derived cells	44:62	Global mapping of glycosylation pathways in human-derived cells.
33730547	1	19	theme	biological	163:172	arg1	phenomena					174:182	biological phenomena	163:182	biological phenomena	163:182	Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena.
33730547	0	20	theme	Global	0:5	arg1	mapping					7:13	Global mapping	0:13	Global mapping of glycosylation pathways in human-derived cells	0:62	Global mapping of glycosylation pathways in human-derived cells.
33730547	8	21	theme	glycan	1052:1057	arg1	analyses					1059:1066	glycan analyses	1052:1066	glycan analyses	1052:1066	Our systematic approach can accelerate glycan analyses and engineering in mammalian cells.
33730547	6	22	theme	cell	781:784	arg1	lines					786:790	40 knockout HEK293 cell lines	762:790	40 knockout HEK293 cell lines	762:790	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	1	23	theme	phenomena	174:182	arg1	range					154:158	a broad range	146:158	a broad range of biological phenomena	146:182	Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena.
33730547	0	24	theme	glycosylation	18:30	arg1	pathways					32:39	glycosylation pathways	18:39	glycosylation pathways	18:39	Global mapping of glycosylation pathways in human-derived cells.
33730547	6	25	theme	HEK293	774:779	arg1	lines					786:790	40 knockout HEK293 cell lines	762:790	40 knockout HEK293 cell lines	762:790	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	2	26	theme	environmental	279:291	arg1	changes					293:299	environmental changes	279:299	environmental changes	279:299	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	7	27	theme	tumor	935:939	arg1	tissues					941:947	primary colon tumor tissues	921:947	primary colon tumor tissues	921:947	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	4	28	dep	informatically	457:470	arg1	selected					472:479	selected	472:479	informatically selected 950 genes involved in glycosylation and its regulation	457:534	We informatically selected 950 genes involved in glycosylation and its regulation.
33730547	1	29	theme	classes	100:106	arg1	one					77:79	one	77:79	one	77:79	Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena.
33730547	1	29	theme	classes	100:106	arg1	classes					100:106	the fundamental classes	84:106	the fundamental classes of macromolecules	84:124	Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena.
33730547	8	30	theme	mammalian	1087:1095	arg1	cells					1097:1101	mammalian cells	1087:1101	mammalian cells	1087:1101	Our systematic approach can accelerate glycan analyses and engineering in mammalian cells.
33730547	3	31	theme	glycan	410:415	arg1	structures					417:426	glycan structures	410:426	glycan structures based on gene expression	410:451	Here, we developed a comprehensive glycosylation mapping tool, termed GlycoMaple, to visualize and estimate glycan structures based on gene expression.
33730547	0	32	theme	pathways	32:39	arg1	mapping					7:13	Global mapping	0:13	Global mapping of glycosylation pathways in human-derived cells	0:62	Global mapping of glycosylation pathways in human-derived cells.
33730547	2	33	theme	structures	211:220	arg1	structures					211:220	glycan structures	204:220	glycan structures	204:220	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	2	33	theme	structures	211:220	arg1	variety					193:199	A large variety	185:199	A large variety of glycan structures	185:220	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	5	34	theme	Expression	537:546	arg1	profiles					548:555	Expression profiles	537:555	Expression profiles of these genes	537:570	Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses.
33730547	3	35	theme	gene	437:440	arg1	expression					442:451	gene expression	437:451	gene expression	437:451	Here, we developed a comprehensive glycosylation mapping tool, termed GlycoMaple, to visualize and estimate glycan structures based on gene expression.
33730547	2	36	theme	glycan	204:209	arg1	structures					211:220	glycan structures	204:220	glycan structures	204:220	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	0	37	theme	human-derived	44:56	arg1	cells					58:62	human-derived cells	44:62	human-derived cells	44:62	Global mapping of glycosylation pathways in human-derived cells.
33730547	5	38	theme	glycomic	679:686	arg1	analyses					688:695	glycomic analyses	679:695	glycomic analyses	679:695	Expression profiles of these genes were mapped onto global glycan metabolic pathways to predict glycan structures, which were confirmed using glycomic analyses.
33730547	6	39	theme	glycan	837:842	arg1	structures					844:853	glycan structures	837:853	glycan structures	837:853	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	1	40	theme	macromolecules	111:124	arg1	classes					100:106	the fundamental classes	84:106	the fundamental classes of macromolecules	84:124	Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena.
33730547	7	41	theme	lines	898:902	arg1	structures					876:885	the glycan structures	865:885	the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues	865:947	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	7	42	theme	tissues	908:914	arg1	structures					876:885	the glycan structures	865:885	the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues	865:947	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	2	43	theme	large	187:191	arg1	structures					211:220	glycan structures	204:220	glycan structures	204:220	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	2	43	theme	large	187:191	arg1	variety					193:199	A large variety	185:199	A large variety of glycan structures	185:220	A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes.
33730547	7	44	theme	tissues	941:947	arg1	structures					876:885	the glycan structures	865:885	the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues	865:947	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	1	45	theme	fundamental	88:98	arg1	classes					100:106	the fundamental classes	84:106	the fundamental classes of macromolecules	84:124	Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena.
33730547	6	46	theme	knockout	825:832	arg1	gene					820:823	gene knockout	820:832	gene knockout	820:832	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	6	47	theme	knockout	765:772	arg1	lines					786:790	40 knockout HEK293 cell lines	762:790	40 knockout HEK293 cell lines	762:790	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	6	48	theme	gene	820:823	arg1	effects					809:815	the effects	805:815	the effects of gene knockout on glycan structures	805:853	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	6	49	theme	processing	735:744	arg1	predictions					711:721	the predictions	707:721	the predictions of N-glycan processing	707:744	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
33730547	7	50	theme	cell	893:896	arg1	lines					898:902	64 cell lines	890:902	64 cell lines	890:902	Finally, the glycan structures of 64 cell lines, 37 tissues, and primary colon tumor tissues were estimated and compared using publicly available databases.
33730547	6	51	theme	N-glycan	726:733	arg1	processing					735:744	N-glycan processing	726:744	N-glycan processing	726:744	Based on the predictions of N-glycan processing, we constructed 40 knockout HEK293 cell lines and analyzed the effects of gene knockout on glycan structures.
34341581	2	0	theme	intact	349:354	arg1	glycopeptides					356:368	intact glycopeptides	349:368	intact glycopeptides using tandem mass spectrometry	349:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	5	1	theme	glycan	981:986	arg1	structures					988:997	rare/new glycan structures	972:997	rare/new glycan structures	972:997	Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures.
34341581	5	2	theme	mapping	907:913	arg1	strategy					915:922	the database-independent glycan mapping strategy	875:922	the database-independent glycan mapping strategy	875:922	Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures.
34341581	1	3	theme	site-specific	162:174	arg1	level					176:180	structural and site-specific level	147:180	structural and site-specific level	147:180	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	4	4	theme	distinct	589:596	arg1	patterns					598:605	distinct patterns	589:605	distinct patterns of Y ions	589:615	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	0	5	theme	modularization	90:103	arg1	strategy					105:112	a modularization strategy	88:112	a modularization strategy	88:112	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	2	6	from	interpretation	308:321	arg1	glycopeptides					356:368	intact glycopeptides	349:368	intact glycopeptides using tandem mass spectrometry	349:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	2	7	theme	modularization	272:285	arg1	strategy					287:294	a modularization strategy	270:294	a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry	270:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	5	8	theme	rare/new	972:979	arg1	structures					988:997	rare/new glycan structures	972:997	rare/new glycan structures	972:997	Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures.
34341581	4	9	theme	Y	610:610	arg1	ions					612:615	Y ions	610:615	Y ions	610:615	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	4	10	with	structures	827:836	arg1	subtypes					856:863	three glycan subtypes	843:863	three glycan subtypes	843:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	5	11	theme	structures	988:997	arg1	identification					954:967	the identification	950:967	the identification of rare/new glycan structures	950:997	Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures.
34341581	4	12	theme	glycan	708:713	arg1	structures					715:724	detailed glycan structures	699:724	detailed glycan structures	699:724	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	2	13	dep	de	300:301	arg1	novo					303:306	novo	303:306	novo	303:306	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	4	14	theme	detailed	699:706	arg1	structures					715:724	detailed glycan structures	699:724	detailed glycan structures	699:724	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	1	15	theme	Precision	115:123	arg1	mapping					125:131	Precision mapping	115:131	Precision mapping of glycans at structural and site-specific level	115:180	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	0	16	gly	glycoproteins	68:80	arg1	glycoproteins					68:80	glycoproteins	68:80	glycoproteins using a modularization strategy	68:112	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	6	17	theme	biomedical	1109:1118	arg1	research					1120:1127	the biomedical research	1105:1127	the biomedical research	1105:1127	The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.
34341581	4	18	with	types	789:793	arg1	subtypes					856:863	three glycan subtypes	843:863	three glycan subtypes	843:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	0	19	from	sequencing	28:37	arg1	glycoproteins					68:80	glycoproteins	68:80	glycoproteins using a modularization strategy	68:112	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	4	20	from	brain	762:766	arg1	thousands					729:737	thousands	729:737	thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes	729:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	6	21	theme	in-depth	1044:1051	arg1	study					1079:1083	in-depth structural and functional study	1044:1083	in-depth structural and functional study of glycoproteins in the biomedical research	1044:1127	The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.
34341581	2	22	theme	mass	383:386	arg1	spectrometry					388:399	tandem mass spectrometry	376:399	tandem mass spectrometry	376:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	6	23	theme	structural	1053:1062	arg1	study					1079:1083	in-depth structural and functional study	1044:1083	in-depth structural and functional study of glycoproteins in the biomedical research	1044:1127	The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.
34341581	4	24	theme	glycan	849:854	arg1	subtypes					856:863	three glycan subtypes	843:863	three glycan subtypes	843:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	2	25	theme	de	300:301	arg1	interpretation					308:321	de novo interpretation	300:321	de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry	300:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	2	26	theme	tandem	376:381	arg1	spectrometry					388:399	tandem mass spectrometry	376:399	tandem mass spectrometry	376:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	4	27	theme	glycosites	742:751	arg1	thousands					729:737	thousands	729:737	thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes	729:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	2	28	gly	glycopeptides	356:368	arg2	glycopeptides					356:368	intact glycopeptides	349:368	intact glycopeptides using tandem mass spectrometry	349:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	4	29	from	glycosites	742:751	arg1	brain					762:766	mouse brain	756:766	mouse brain	756:766	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	6	30	theme	functional	1068:1077	arg1	study					1079:1083	in-depth structural and functional study	1044:1083	in-depth structural and functional study of glycoproteins in the biomedical research	1044:1127	The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.
34341581	3	31	theme	interpretation	463:476	arg1	process					478:484	the interpretation process	459:484	the interpretation process	459:484	An algorithm named StrucGP is also developed to automate the interpretation process for large-scale analysis.
34341581	0	32	theme	de	9:10	arg1	sequencing					28:37	de novo structural sequencing	9:37	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.	0:113	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	4	33	theme	mouse	756:760	arg1	brain					762:766	mouse brain	756:766	mouse brain	756:766	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	5	34	theme	database-independent	879:898	arg1	strategy					915:922	the database-independent glycan mapping strategy	875:922	the database-independent glycan mapping strategy	875:922	Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures.
34341581	4	35	theme	structures	715:724	arg1	determination					682:694	determination	682:694	determination of detailed glycan structures	682:724	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	4	36	theme	ions	657:660	arg1	module					576:581	each module	571:581	each module using distinct patterns of Y ions	571:615	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	4	36	theme	ions	657:660	arg1	combination					622:632	a combination	620:632	a combination of distinguishable B/Y ions	620:660	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	6	37	theme	glycoproteins	1088:1100	arg1	study					1079:1083	in-depth structural and functional study	1044:1083	in-depth structural and functional study of glycoproteins in the biomedical research	1044:1127	The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.
34341581	1	38	theme	most	202:205	arg1	tasks					219:223	the most challenging tasks	198:223	the most challenging tasks in the glycobiology field	198:249	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	0	39	theme	structural	17:26	arg1	sequencing					28:37	de novo structural sequencing	9:37	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.	0:113	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	1	40	theme	challenging	207:217	arg1	tasks					219:223	the most challenging tasks	198:223	the most challenging tasks in the glycobiology field	198:249	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	0	41	theme	site-specific	42:54	arg1	N-glycan					56:63	site-specific N-glycan	42:63	site-specific N-glycan	42:63	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	4	42	gly	glycosites	742:751	arg2	glycosites					742:751	glycosites	742:751	glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes	742:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	6	43	from	study	1079:1083	arg1	research					1120:1127	the biomedical research	1105:1127	the biomedical research	1105:1127	The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.
34341581	6	44	gly	glycoproteins	1088:1100	arg1	glycoproteins					1088:1100	glycoproteins	1088:1100	glycoproteins	1088:1100	The approach will be greatly beneficial for in-depth structural and functional study of glycoproteins in the biomedical research.
34341581	2	45	theme	structures	335:344	arg1	interpretation					308:321	de novo interpretation	300:321	de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry	300:399	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	4	46	theme	branch	820:825	arg1	structures					827:836	17 branch structures	817:836	17 branch structures with three glycan subtypes	817:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	2	47	theme	N-glycan	326:333	arg1	structures					335:344	N-glycan structures	326:344	N-glycan structures	326:344	Here, we describe a modularization strategy for de novo interpretation of N-glycan structures on intact glycopeptides using tandem mass spectrometry.
34341581	4	48	theme	core	798:801	arg1	structure					803:811	core structure	798:811	core structure	798:811	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	1	49	from	tasks	219:223	arg1	field					245:249	the glycobiology field	228:249	the glycobiology field	228:249	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	4	50	from	thousands	729:737	arg1	brain					762:766	mouse brain	756:766	mouse brain	756:766	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	1	51	theme	tasks	219:223	arg1	tasks					219:223	the most challenging tasks	198:223	the most challenging tasks in the glycobiology field	198:249	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	1	51	theme	tasks	219:223	arg1	one					191:193	one	191:193	one	191:193	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	0	52	dep	de	9:10	arg1	novo					12:15	novo	12:15	novo	12:15	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	1	53	theme	glycans	136:142	arg1	mapping					125:131	Precision mapping	115:131	Precision mapping of glycans at structural and site-specific level	115:180	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	4	54	theme	ions	612:615	arg1	patterns					598:605	distinct patterns	589:605	distinct patterns of Y ions	589:615	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	4	55	theme	B/Y	653:655	arg1	ions					657:660	distinguishable B/Y ions	637:660	distinguishable B/Y ions	637:660	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	4	56	theme	structure	803:811	arg1	types					789:793	four types	784:793	four types of core structure	784:811	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	4	56	theme	structure	803:811	arg1	structures					827:836	17 branch structures	817:836	17 branch structures with three glycan subtypes	817:863	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	4	57	theme	distinguishable	637:651	arg1	ions					657:660	distinguishable B/Y ions	637:660	distinguishable B/Y ions	637:660	By dividing an N-glycan into three modules and identifying each module using distinct patterns of Y ions or a combination of distinguishable B/Y ions, the method enables determination of detailed glycan structures on thousands of glycosites in mouse brain, which comprise four types of core structure and 17 branch structures with three glycan subtypes.
34341581	5	58	theme	glycan	900:905	arg1	strategy					915:922	the database-independent glycan mapping strategy	875:922	the database-independent glycan mapping strategy	875:922	Owing to the database-independent glycan mapping strategy, StrucGP also facilitates the identification of rare/new glycan structures.
34341581	3	59	theme	large-scale	490:500	arg1	analysis					502:509	large-scale analysis	490:509	large-scale analysis	490:509	An algorithm named StrucGP is also developed to automate the interpretation process for large-scale analysis.
34341581	0	60	theme	N-glycan	56:63	arg1	sequencing					28:37	de novo structural sequencing	9:37	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.	0:113	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	0	61	dep	StrucGP	0:6	arg1	sequencing					28:37	de novo structural sequencing	9:37	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.	0:113	StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy.
34341581	1	62	from	level	176:180	arg1	mapping					125:131	Precision mapping	115:131	Precision mapping of glycans at structural and site-specific level	115:180	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	1	63	theme	structural	147:156	arg1	level					176:180	structural and site-specific level	147:180	structural and site-specific level	147:180	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
34341581	1	64	theme	glycobiology	232:243	arg1	field					245:249	the glycobiology field	228:249	the glycobiology field	228:249	Precision mapping of glycans at structural and site-specific level is still one of the most challenging tasks in the glycobiology field.
33610554	8	0	theme	N-cadherin	1261:1270	arg1	abundance					1248:1256	an increased abundance	1235:1256	an increased abundance of N-cadherin (N-Cdh)	1235:1278	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	10	1	theme	possible	1655:1662	arg1	mechanism					1674:1682	a possible molecular mechanism	1653:1682	a possible molecular mechanism underlying the observed phenotype	1653:1716	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	1	2	from	Defects	91:97	arg1	O-mannosylation					110:124	protein O-mannosylation	102:124	protein O-mannosylation	102:124	Defects in protein O-mannosylation lead to severe congenital muscular dystrophies collectively known as α-dystroglycanopathy.
33610554	5	3	theme	specific	739:746	arg1	consequences					758:769	specific molecular consequences	739:769	specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion	739:813	However, specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion are largely unknown.
33610554	10	4	theme	p38	1495:1497	arg1	pathways					1509:1516	ERK1/2 and p38 signaling pathways	1484:1516	ERK1/2 and p38 signaling pathways	1484:1516	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	9	5	from	structures	1332:1341	arg1	N-Cdh					1374:1378	N-Cdh	1374:1378	N-Cdh	1374:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	9	5	from	structures	1332:1341	arg1	domain					1364:1369	the extracellular domain	1346:1369	the extracellular domain of N-Cdh	1346:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	11	6	from	changes	1946:1952	arg1	O-mannosylation					1957:1971	O-mannosylation	1957:1971	O-mannosylation	1957:1971	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	9	7	located	detected	1385:1392	arg1	addition					1284:1291	addition	1284:1291	addition	1284:1291	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	9	7	located	detected	1385:1392	arg2	changes					1308:1314	site-specific changes	1294:1314	site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh	1294:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	10	8	theme	transcriptional	1536:1550	arg1	changes					1552:1558	transcriptional changes	1536:1558	transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT)	1536:1627	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	2	9	theme	cell	326:329	arg1	adhesion					331:338	cell adhesion	326:338	cell adhesion to the extracellular matrix	326:366	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	11	10	from	O-mannosylation	1957:1971	arg1	impact					1936:1941	the impact	1932:1941	the impact of changes in O-mannosylation on N-glycosylation	1932:1990	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	9	11	from	impact	1412:1417	arg1	interactions					1432:1443	homotypic interactions	1422:1443	homotypic interactions	1422:1443	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	11	12	theme	changes	1946:1952	arg1	impact					1936:1941	the impact	1932:1941	the impact of changes in O-mannosylation on N-glycosylation	1932:1990	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	2	13	theme	extracellular	347:359	arg1	matrix					361:366	the extracellular matrix	343:366	the extracellular matrix	343:366	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	4	14	from	defects	710:716	arg1	POMGNT1					721:727	POMGNT1	721:727	POMGNT1	721:727	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	11	15	from	impact	1936:1941	arg1	O-mannosylation					1957:1971	O-mannosylation	1957:1971	O-mannosylation	1957:1971	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	11	15	from	impact	1936:1941	arg1	N-glycosylation					1976:1990	N-glycosylation	1976:1990	N-glycosylation	1976:1990	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	2	16	theme	matriglycan	281:291	arg1	hallmark					219:226	A hallmark	217:226	A hallmark of these diseases	217:244	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	2	16	theme	matriglycan	281:291	arg1	loss					253:256	the loss	249:256	the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix	249:366	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	7	17	theme	POMGNT1	1113:1119	arg1	activity					1121:1128	POMGNT1 activity	1113:1128	POMGNT1 activity	1113:1128	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion.
33610554	6	18	theme	MEB	899:901	arg1	patient					903:909	an MEB patient	896:909	an MEB patient	896:909	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	9	19	from	changes	1308:1314	arg1	structures					1332:1341	the N-glycan structures	1319:1341	the N-glycan structures in the extracellular domain of N-Cdh	1319:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	7	20	theme	cell-cell	1142:1150	arg1	adhesion					1152:1159	cell-cell adhesion	1142:1159	cell-cell adhesion	1142:1159	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion.
33610554	9	21	theme	N-Cdh	1374:1378	arg1	N-Cdh					1374:1378	N-Cdh	1374:1378	N-Cdh	1374:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	9	21	theme	N-Cdh	1374:1378	arg1	domain					1364:1369	the extracellular domain	1346:1369	the extracellular domain of N-Cdh	1346:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	3	22	theme	O-mannose	390:398	arg1	β1,2-N-acetylglucosaminyltransferase					400:435	protein O-mannose β1,2-N-acetylglucosaminyltransferase 1	382:437	protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1)	382:447	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	3	22	theme	O-mannose	390:398	arg1	POMGNT1					440:446	POMGNT1	440:446	POMGNT1	440:446	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	6	23	used	used	839:842	arg2	We					836:837	We	836:837	We	836:837	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	5	24	theme	POMGNT1	774:780	arg1	deficiency					782:791	POMGNT1 deficiency	774:791	POMGNT1 deficiency	774:791	However, specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion are largely unknown.
33610554	2	25	theme	diseases	237:244	arg1	hallmark					219:226	A hallmark	217:226	A hallmark of these diseases	217:244	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	2	25	theme	diseases	237:244	arg1	loss					253:256	the loss	249:256	the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix	249:366	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	9	26	theme	homotypic	1422:1430	arg1	interactions					1432:1443	homotypic interactions	1422:1443	homotypic interactions	1422:1443	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	10	27	with	comparable	1569:1578	arg1	EMT					1624:1626	EMT	1624:1626	EMT	1624:1626	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	10	27	with	comparable	1569:1578	arg1	transition					1612:1621	the epithelial-mesenchymal transition	1585:1621	the epithelial-mesenchymal transition (EMT)	1585:1627	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	3	28	theme	O-mannosyl	489:498	arg1	glycans					500:506	O-mannosyl glycans	489:506	O-mannosyl glycans	489:506	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	0	29	theme	Glycosyltransferase	0:18	arg1	deficiency					28:37	Glycosyltransferase POMGNT1 deficiency	0:37	Glycosyltransferase POMGNT1 deficiency	0:37	Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion.
33610554	4	30	theme	matrix	619:624	arg1	adhesion					626:633	cell-extracellular matrix adhesion	600:633	cell-extracellular matrix adhesion	600:633	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	8	31	theme	altered	1186:1192	arg1	due					1228:1230	due	1228:1230	due	1228:1230	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	8	31	theme	altered	1186:1192	arg1	properties					1213:1222	the altered intrinsic adhesion properties	1182:1222	the altered intrinsic adhesion properties	1182:1222	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	1	32	theme	congenital	141:150	arg1	dystrophies					161:171	severe congenital muscular dystrophies	134:171	severe congenital muscular dystrophies collectively known as α-dystroglycanopathy	134:214	Defects in protein O-mannosylation lead to severe congenital muscular dystrophies collectively known as α-dystroglycanopathy.
33610554	0	33	theme	N-cadherin-mediated	51:69	arg1	adhesion					81:88	N-cadherin-mediated cell-cell adhesion	51:88	N-cadherin-mediated cell-cell adhesion	51:88	Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion.
33610554	8	34	theme	adhesion	1204:1211	arg1	due					1228:1230	due	1228:1230	due	1228:1230	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	8	34	theme	adhesion	1204:1211	arg1	properties					1213:1222	the altered intrinsic adhesion properties	1182:1222	the altered intrinsic adhesion properties	1182:1222	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	11	35	theme	complex	1846:1852	arg1	symptoms					1863:1870	the complex clinical symptoms	1842:1870	the complex clinical symptoms of MEB or α-dystroglycanopathy	1842:1901	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	6	36	theme	POMGNT1	844:850	arg1	cells					869:873	POMGNT1 knockout HEK293T cells	844:873	POMGNT1 knockout HEK293T cells	844:873	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	11	37	theme	α-dystroglycanopathy	1882:1901	arg1	symptoms					1863:1870	the complex clinical symptoms	1842:1870	the complex clinical symptoms of MEB or α-dystroglycanopathy	1842:1901	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	3	38	theme	muscle-eye-brain	542:557	arg1	MEB					560:562	MEB	560:562	MEB	560:562	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	3	38	theme	muscle-eye-brain	542:557	arg1	disease					565:571	muscle-eye-brain (MEB) disease	542:571	muscle-eye-brain (MEB) disease	542:571	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	7	39	theme	biological	1010:1019	arg1	techniques					1021:1030	Biochemical and molecular biological techniques	984:1030	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics	984:1087	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion.
33610554	11	40	theme	MEB	1875:1877	arg1	symptoms					1863:1870	the complex clinical symptoms	1842:1870	the complex clinical symptoms of MEB or α-dystroglycanopathy	1842:1901	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	11	41	theme	cell-cell	1773:1781	arg1	adhesion					1783:1790	cadherin-mediated cell-cell adhesion	1755:1790	cadherin-mediated cell-cell adhesion	1755:1790	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	8	42	theme	increased	1238:1246	arg1	abundance					1248:1256	an increased abundance	1235:1256	an increased abundance of N-cadherin (N-Cdh)	1235:1278	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	10	43	theme	molecular	1664:1672	arg1	mechanism					1674:1682	a possible molecular mechanism	1653:1682	a possible molecular mechanism underlying the observed phenotype	1653:1716	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	11	44	theme	EMT-related	1802:1812	arg1	processes					1814:1822	other EMT-related processes	1796:1822	other EMT-related processes	1796:1822	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	10	45	theme	POMGNT1-deficient	1459:1475	arg1	cells					1477:1481	POMGNT1-deficient cells	1459:1481	POMGNT1-deficient cells	1459:1481	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	4	46	theme	cell-cell	645:653	arg1	adhesion					655:662	aberrant cell-cell adhesion	636:662	aberrant cell-cell adhesion	636:662	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	10	47	theme	signaling	1499:1507	arg1	pathways					1509:1516	ERK1/2 and p38 signaling pathways	1484:1516	ERK1/2 and p38 signaling pathways	1484:1516	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	10	48	theme	observed	1699:1706	arg1	phenotype					1708:1716	the observed phenotype	1695:1716	the observed phenotype	1695:1716	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	9	49	theme	site-specific	1294:1306	arg1	changes					1308:1314	site-specific changes	1294:1314	site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh	1294:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	11	50	from	changes	1744:1750	arg1	adhesion					1783:1790	cadherin-mediated cell-cell adhesion	1755:1790	cadherin-mediated cell-cell adhesion	1755:1790	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	11	50	from	changes	1744:1750	arg1	processes					1814:1822	other EMT-related processes	1796:1822	other EMT-related processes	1796:1822	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	2	51	from	loss	253:256	arg1	α-dystroglycan					296:309	α-dystroglycan	296:309	α-dystroglycan	296:309	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	6	52	theme	POMGNT1	964:970	arg1	deficiency					972:981	POMGNT1 deficiency	964:981	POMGNT1 deficiency	964:981	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	6	53	from	changes	953:959	arg1	deficiency					972:981	POMGNT1 deficiency	964:981	POMGNT1 deficiency	964:981	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	5	54	theme	deficiency	782:791	arg1	consequences					758:769	specific molecular consequences	739:769	specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion	739:813	However, specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion are largely unknown.
33610554	9	55	theme	N-glycan	1323:1330	arg1	structures					1332:1341	the N-glycan structures	1319:1341	the N-glycan structures in the extracellular domain of N-Cdh	1319:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	5	56	theme	cell-cell	796:804	arg1	adhesion					806:813	cell-cell adhesion	796:813	cell-cell adhesion	796:813	However, specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion are largely unknown.
33610554	5	57	theme	molecular	748:756	arg1	consequences					758:769	specific molecular consequences	739:769	specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion	739:813	However, specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion are largely unknown.
33610554	9	58	theme	extracellular	1350:1362	arg1	N-Cdh					1374:1378	N-Cdh	1374:1378	N-Cdh	1374:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	9	58	theme	extracellular	1350:1362	arg1	domain					1364:1369	the extracellular domain	1346:1369	the extracellular domain of N-Cdh	1346:1378	In addition, site-specific changes in the N-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions.
33610554	2	59	theme	O-mannose-bound	265:279	arg1	matriglycan					281:291	the O-mannose-bound matriglycan	261:291	the O-mannose-bound matriglycan	261:291	A hallmark of these diseases is the loss of the O-mannose-bound matriglycan on α-dystroglycan, which reduces cell adhesion to the extracellular matrix.
33610554	7	60	theme	activity	1121:1128	arg1	lack					1105:1108	a lack	1103:1108	a lack of POMGNT1 activity	1103:1128	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion.
33610554	1	61	theme	muscular	152:159	arg1	dystrophies					161:171	severe congenital muscular dystrophies	134:171	severe congenital muscular dystrophies collectively known as α-dystroglycanopathy	134:214	Defects in protein O-mannosylation lead to severe congenital muscular dystrophies collectively known as α-dystroglycanopathy.
33610554	6	62	theme	HEK293T	861:867	arg1	cells					869:873	POMGNT1 knockout HEK293T cells	844:873	POMGNT1 knockout HEK293T cells	844:873	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	3	63	theme	protein	382:388	arg1	β1,2-N-acetylglucosaminyltransferase					400:435	protein O-mannose β1,2-N-acetylglucosaminyltransferase 1	382:437	protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1)	382:447	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	3	63	theme	protein	382:388	arg1	POMGNT1					440:446	POMGNT1	440:446	POMGNT1	440:446	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	10	64	theme	ERK1/2	1484:1489	arg1	pathways					1509:1516	ERK1/2 and p38 signaling pathways	1484:1516	ERK1/2 and p38 signaling pathways	1484:1516	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	1	65	theme	protein	102:108	arg1	O-mannosylation					110:124	protein O-mannosylation	102:124	protein O-mannosylation	102:124	Defects in protein O-mannosylation lead to severe congenital muscular dystrophies collectively known as α-dystroglycanopathy.
33610554	10	66	theme	epithelial-mesenchymal	1589:1610	arg1	EMT					1624:1626	EMT	1624:1626	EMT	1624:1626	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	10	66	theme	epithelial-mesenchymal	1589:1610	arg1	transition					1612:1621	the epithelial-mesenchymal transition	1585:1621	the epithelial-mesenchymal transition (EMT)	1585:1627	Moreover, in POMGNT1-deficient cells, ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable with the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype.
33610554	0	67	theme	POMGNT1	20:26	arg1	deficiency					28:37	Glycosyltransferase POMGNT1 deficiency	0:37	Glycosyltransferase POMGNT1 deficiency	0:37	Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion.
33610554	6	68	from	patient	903:909	arg1	fibroblasts					879:889	fibroblasts	879:889	fibroblasts	879:889	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	6	68	from	patient	903:909	arg1	cells					869:873	POMGNT1 knockout HEK293T cells	844:873	POMGNT1 knockout HEK293T cells	844:873	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	3	69	theme	glycans	500:506	arg1	elongation					475:484	the elongation	471:484	the elongation of O-mannosyl glycans	471:506	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	8	70	theme	intrinsic	1194:1202	arg1	due					1228:1230	due	1228:1230	due	1228:1230	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	8	70	theme	intrinsic	1194:1202	arg1	properties					1213:1222	the altered intrinsic adhesion properties	1182:1222	the altered intrinsic adhesion properties	1182:1222	We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh).
33610554	1	71	theme	severe	134:139	arg1	dystrophies					161:171	severe congenital muscular dystrophies	134:171	severe congenital muscular dystrophies collectively known as α-dystroglycanopathy	134:214	Defects in protein O-mannosylation lead to severe congenital muscular dystrophies collectively known as α-dystroglycanopathy.
33610554	4	72	theme	aberrant	636:643	arg1	adhesion					655:662	aberrant cell-cell adhesion	636:662	aberrant cell-cell adhesion	636:662	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	11	73	theme	clinical	1854:1861	arg1	symptoms					1863:1870	the complex clinical symptoms	1842:1870	the complex clinical symptoms of MEB or α-dystroglycanopathy	1842:1901	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	0	74	theme	cell-cell	71:79	arg1	adhesion					81:88	N-cadherin-mediated cell-cell adhesion	51:88	N-cadherin-mediated cell-cell adhesion	51:88	Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion.
33610554	6	75	theme	molecular	943:951	arg1	changes					953:959	the molecular changes	939:959	the molecular changes in POMGNT1 deficiency	939:981	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	4	76	located	observed	686:693	arg2	adhesion					655:662	aberrant cell-cell adhesion	636:662	aberrant cell-cell adhesion	636:662	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	4	76	located	observed	686:693	arg1	response					698:705	response	698:705	response to defects in POMGNT1	698:727	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	6	77	theme	knockout	852:859	arg1	cells					869:873	POMGNT1 knockout HEK293T cells	844:873	POMGNT1 knockout HEK293T cells	844:873	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	4	78	from	defects	589:595	arg1	adhesion					626:633	cell-extracellular matrix adhesion	600:633	cell-extracellular matrix adhesion	600:633	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	4	79	theme	cell-extracellular	600:617	arg1	adhesion					626:633	cell-extracellular matrix adhesion	600:633	cell-extracellular matrix adhesion	600:633	In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1.
33610554	7	80	theme	molecular	1000:1008	arg1	techniques					1021:1030	Biochemical and molecular biological techniques	984:1030	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics	984:1087	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion.
33610554	6	81	theme	deeper	919:924	arg1	insight					926:932	deeper insight	919:932	deeper insight into the molecular changes in POMGNT1 deficiency	919:981	We used POMGNT1 knockout HEK293T cells and fibroblasts from an MEB patient to gain deeper insight into the molecular changes in POMGNT1 deficiency.
33610554	11	82	theme	cadherin-mediated	1755:1771	arg1	adhesion					1783:1790	cadherin-mediated cell-cell adhesion	1755:1790	cadherin-mediated cell-cell adhesion	1755:1790	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	7	83	theme	Biochemical	984:994	arg1	techniques					1021:1030	Biochemical and molecular biological techniques	984:1030	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics	984:1087	Biochemical and molecular biological techniques combined with proteomics, glycoproteomics, and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion.
33610554	11	84	theme	other	1796:1800	arg1	processes					1814:1822	other EMT-related processes	1796:1822	other EMT-related processes	1796:1822	Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general and suggests that the impact of changes in O-mannosylation on N-glycosylation has been underestimated.
33610554	3	85	from	Mutations	369:377	arg1	β1,2-N-acetylglucosaminyltransferase					400:435	protein O-mannose β1,2-N-acetylglucosaminyltransferase 1	382:437	protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1)	382:447	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	3	85	from	Mutations	369:377	arg1	POMGNT1					440:446	POMGNT1	440:446	POMGNT1	440:446	Mutations in protein O-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation of O-mannosyl glycans, have mainly been associated with muscle-eye-brain (MEB) disease.
33610554	5	86	from	consequences	758:769	arg1	adhesion					806:813	cell-cell adhesion	796:813	cell-cell adhesion	796:813	However, specific molecular consequences of POMGNT1 deficiency on cell-cell adhesion are largely unknown.
34229070	4	0	theme	Targeted	541:548	arg1	approach					553:560	a Targeted MS approach	539:560	a Targeted MS approach	539:560	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	6	1	gly	glycopeptides	948:960	arg1	APP					965:967	APP	965:967	APP	965:967	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	6	1	gly	glycopeptides	948:960	arg2	glycopeptides					948:960	three glycopeptides	942:960	three glycopeptides of APP	942:967	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	3	2	theme	O-glycosylation	456:470	arg1	analysis					440:447	comprehensive analysis	426:447	comprehensive analysis of APP O-glycosylation	426:470	Therefore, comprehensive analysis of APP O-glycosylation is important for understanding its functions.
34229070	11	3	dep	processing	1869:1878	arg1	the					1865:1867	the	1865:1867	the	1865:1867	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	7	4	from	domain	1216:1221	arg1	region					1273:1278	the region	1269:1278	the region close to β-cleavage site	1269:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	5	theme	dense	1142:1146	arg1	cluster					1148:1154	a dense cluster	1140:1154	a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site	1140:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	1	6	theme	precursor	187:195	arg1	protein					197:203	amyloid precursor protein	179:203	amyloid precursor protein (APP) into amyloid β peptide (Aβ)	179:237	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	6	theme	precursor	187:195	arg1	APP					206:208	APP	206:208	APP	206:208	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	4	7	theme	O-glycosylation	646:660	arg1	profiling					662:670	O-glycosylation profiling	646:670	O-glycosylation profiling of APP695 expressed in HEK-293 T cells	646:709	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	11	8	from	structures	1774:1783	arg1	APP					1788:1790	APP	1788:1790	APP	1788:1790	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	6	9	theme	APP	965:967	arg1	glycopeptides					948:960	three glycopeptides	942:960	three glycopeptides of APP	942:967	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	1	10	theme	amyloid	216:222	arg1	Aβ					235:236	Aβ	235:236	Aβ	235:236	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	10	theme	amyloid	216:222	arg1	peptide					226:232	amyloid β peptide	216:232	amyloid β peptide (Aβ)	216:237	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	4	11	theme	HEK-293 T	695:703	arg1	cells					705:709	HEK-293 T cells	695:709	HEK-293 T cells	695:709	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	6	12	theme	Tn	1016:1017	arg1	GalNAc					1008:1013	GalNAc	1008:1013	GalNAc (Tn antigen)	1008:1026	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	6	12	theme	Tn	1016:1017	arg1	antigen					1019:1025	Tn antigen	1016:1025	Tn antigen	1016:1025	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	8	13	theme	HEK-293 T	1421:1429	arg1	cell					1431:1434	HEK-293 T cell	1421:1434	HEK-293 T cell	1421:1434	Moreover, we also observed that TNF-α could upregulate the expression of APP and the truncated O-glycans on APP in HEK-293 T cell.
34229070	11	14	theme	accurate	1739:1746	arg1	O-glycosites					1748:1759	accurate O-glycosites	1739:1759	accurate O-glycosites	1739:1759	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	7	15	theme	nearby	1193:1198	arg1	beginning					1200:1208	the region nearby beginning	1182:1208	the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site	1182:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	1	16	theme	proteolytic	153:163	arg1	step					262:265	a critical step	251:265	a critical step in the pathogenesis of Alzheimer's disease (AD)	251:313	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	16	theme	proteolytic	153:163	arg1	processing					165:174	The aberrant proteolytic processing	140:174	The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain	140:246	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	5	17	theme	relative	726:733	arg1	abundance					735:743	relative abundance	726:743	relative abundance of glycopeptides with various O-glycosites and O-glycans	726:800	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	5	18	theme	various	767:773	arg1	O-glycosites					775:786	various O-glycosites	767:786	various O-glycosites	767:786	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	1	19	from	processing	165:174	arg1	brain					242:246	brain	242:246	brain	242:246	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	9	20	theme	O-glycopeptide	1480:1493	arg1	strategy					1507:1514	an intact O-glycopeptide MS analysis strategy	1470:1514	an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1470:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	1	21	dep	BACKGROUND	129:138	arg1	step					262:265	a critical step	251:265	a critical step in the pathogenesis of Alzheimer's disease (AD)	251:313	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	21	dep	BACKGROUND	129:138	arg1	processing					165:174	The aberrant proteolytic processing	140:174	The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain	140:246	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	6	22	gly	O-glycosites	910:921	arg2	O-glycosites					910:921	14 O-glycosites	907:921	14 O-glycosites	907:921	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	0	23	theme	targeted	83:90	arg1	strategy					119:126	targeted and multi-fragmentation MS strategy	83:126	targeted and multi-fragmentation MS strategy	83:126	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	7	24	gly	sialylated	1245:1254	arg1	O-glycans					1256:1264	sialylated O-glycans	1245:1264	sialylated O-glycans on the region close to β-cleavage site	1245:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	9	25	theme	analysis	1498:1505	arg1	strategy					1507:1514	an intact O-glycopeptide MS analysis strategy	1470:1514	an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1470:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	10	26	theme	comprehensive	1644:1656	arg1	map					1674:1676	a comprehensive O-glycosylation map	1642:1676	a comprehensive O-glycosylation map of APP expressed in HEK-293 T cell	1642:1711	These results provide a comprehensive O-glycosylation map of APP expressed in HEK-293 T cell.
34229070	0	27	theme	multi-fragmentation	96:114	arg1	strategy					119:126	targeted and multi-fragmentation MS strategy	83:126	targeted and multi-fragmentation MS strategy	83:126	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	4	28	dep	METHODS	518:524	arg1	characterized					632:644	characterized	632:644	characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells	632:709	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	4	28	dep	METHODS	518:524	arg1	developed					529:537	developed	529:537	developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy)	529:612	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	6	29	theme	mono-/di-sialylated	1041:1059	arg1	glycans					1068:1074	mono-/di-sialylated core 1 glycans	1041:1074	mono-/di-sialylated core 1 glycans	1041:1074	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	2	30	gly	O-glycosylated	322:335	arg1	O-glycosylation					346:360	O-glycosylation	346:360	O-glycosylation of APP	346:367	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	2	30	gly	O-glycosylated	322:335	arg1	protein					337:343	an O-glycosylated protein	319:343	an O-glycosylated protein	319:343	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	11	31	theme	APP	1897:1899	arg1	functions					1884:1892	functions	1884:1892	functions	1884:1892	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	11	31	theme	APP	1897:1899	arg1	processing					1869:1878	processing	1869:1878	processing	1869:1878	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	0	32	theme	Comprehensive	0:12	arg1	analysis					14:21	Comprehensive analysis	0:21	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP)	0:75	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	9	33	theme	O-glycopeptide	1524:1537	arg1	identification					1539:1552	APP O-glycopeptide identification	1520:1552	APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1520:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	11	34	gly	O-glycosites	1748:1759	arg2	O-glycosites					1748:1759	accurate O-glycosites	1739:1759	accurate O-glycosites	1739:1759	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	10	35	theme	APP	1681:1683	arg1	map					1674:1676	a comprehensive O-glycosylation map	1642:1676	a comprehensive O-glycosylation map of APP expressed in HEK-293 T cell	1642:1711	These results provide a comprehensive O-glycosylation map of APP expressed in HEK-293 T cell.
34229070	2	36	theme	APP	365:367	arg1	O-glycosylation					346:360	O-glycosylation	346:360	O-glycosylation of APP	346:367	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	2	36	theme	APP	365:367	arg1	protein					337:343	an O-glycosylated protein	319:343	an O-glycosylated protein	319:343	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	9	37	theme	fragmentation	1568:1580	arg1	efficiency					1582:1591	enhanced fragmentation efficiency	1559:1591	enhanced fragmentation efficiency	1559:1591	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	7	38	theme	O-glycans	1256:1264	arg1	domain					1216:1221	E2 domain	1213:1221	E2 domain	1213:1221	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	38	theme	O-glycans	1256:1264	arg1	abundance					1232:1240	high abundance	1227:1240	high abundance	1227:1240	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	38	theme	O-glycans	1256:1264	arg1	O-glycans					1256:1264	sialylated O-glycans	1245:1264	sialylated O-glycans on the region close to β-cleavage site	1245:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	6	39	gly	mono-/di-sialylated	1041:1059	arg1	glycans					1068:1074	mono-/di-sialylated core 1 glycans	1041:1074	mono-/di-sialylated core 1 glycans	1041:1074	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	8	40	from	O-glycans	1401:1409	arg1	APP					1414:1416	APP	1414:1416	APP in HEK-293 T cell	1414:1434	Moreover, we also observed that TNF-α could upregulate the expression of APP and the truncated O-glycans on APP in HEK-293 T cell.
34229070	0	41	theme	precursor	53:61	arg1	APP					72:74	APP	72:74	APP	72:74	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	0	41	theme	precursor	53:61	arg1	protein					63:69	amyloid precursor protein	45:69	amyloid precursor protein (APP)	45:75	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	0	42	gly	O-glycosylation	26:40	arg1	APP					72:74	APP	72:74	APP	72:74	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	0	42	gly	O-glycosylation	26:40	arg1	protein					63:69	amyloid precursor protein	45:69	amyloid precursor protein (APP)	45:75	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	6	43	from	residues	1100:1107	arg1	determinant					1081:1091	determinant	1081:1091	determinant	1081:1091	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	1	44	theme	β	224:224	arg1	Aβ					235:236	Aβ	235:236	Aβ	235:236	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	44	theme	β	224:224	arg1	peptide					226:232	amyloid β peptide	216:232	amyloid β peptide (Aβ)	216:237	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	7	45	from	region	1273:1278	arg1	domain					1216:1221	E2 domain	1213:1221	E2 domain	1213:1221	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	45	from	region	1273:1278	arg1	abundance					1232:1240	high abundance	1227:1240	high abundance	1227:1240	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	45	from	region	1273:1278	arg1	O-glycans					1256:1264	sialylated O-glycans	1245:1264	sialylated O-glycans on the region close to β-cleavage site	1245:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	46	theme	high	1227:1230	arg1	abundance					1232:1240	high abundance	1227:1240	high abundance	1227:1240	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	6	47	dep	RESULTS	888:894	arg1	total					898:902	A total	896:902	RESULTS A total of 14 O-glycosites	888:921	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	10	48	theme	O-glycosylation	1658:1672	arg1	map					1674:1676	a comprehensive O-glycosylation map	1642:1676	a comprehensive O-glycosylation map of APP expressed in HEK-293 T cell	1642:1711	These results provide a comprehensive O-glycosylation map of APP expressed in HEK-293 T cell.
34229070	5	49	theme	TNF-α	871:875	arg1	treatment					877:885	TNF-α treatment	871:885	TNF-α treatment	871:885	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	11	50	theme	O-glycosites	1748:1759	arg1	structures					1774:1783	The accurate O-glycosites and O-glycan structures	1735:1783	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP	1714:1790	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	7	51	theme	domain	1216:1221	arg1	beginning					1200:1208	the region nearby beginning	1182:1208	the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site	1182:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	3	52	theme	APP	452:454	arg1	O-glycosylation					456:470	APP O-glycosylation	452:470	APP O-glycosylation	452:470	Therefore, comprehensive analysis of APP O-glycosylation is important for understanding its functions.
34229070	6	53	theme	O-glycosites	910:921	arg1	total					898:902	A total	896:902	RESULTS A total of 14 O-glycosites	888:921	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	11	54	dep	SIGNIFICANCE	1722:1733	arg1	structures					1774:1783	The accurate O-glycosites and O-glycan structures	1735:1783	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP	1714:1790	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	4	55	theme	MS	550:551	arg1	approach					553:560	a Targeted MS approach	539:560	a Targeted MS approach	539:560	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	1	56	from	step	262:265	arg1	pathogenesis					274:285	the pathogenesis	270:285	the pathogenesis of Alzheimer's disease (AD)	270:313	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	57	theme	amyloid	179:185	arg1	protein					197:203	amyloid precursor protein	179:203	amyloid precursor protein (APP) into amyloid β peptide (Aβ)	179:237	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	57	theme	amyloid	179:185	arg1	APP					206:208	APP	206:208	APP	206:208	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	9	58	with	identification	1539:1552	arg1	efficiency					1582:1591	enhanced fragmentation efficiency	1559:1591	enhanced fragmentation efficiency	1559:1591	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	9	58	with	identification	1539:1552	arg1	sensitivity					1607:1617	detection sensitivity	1597:1617	detection sensitivity	1597:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	1	59	theme	protein	197:203	arg1	step					262:265	a critical step	251:265	a critical step in the pathogenesis of Alzheimer's disease (AD)	251:313	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	59	theme	protein	197:203	arg1	processing					165:174	The aberrant proteolytic processing	140:174	The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain	140:246	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	7	60	from	abundance	1232:1240	arg1	region					1273:1278	the region	1269:1278	the region close to β-cleavage site	1269:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	6	61	theme	Thr577	1123:1128	arg1	Thr577					1123:1128	Thr577	1123:1128	Thr577	1123:1128	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	6	61	theme	Thr577	1123:1128	arg1	Thr576					1112:1117	Thr576	1112:1117	Thr576	1112:1117	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	6	61	theme	Thr577	1123:1128	arg1	residues					1100:1107	the residues	1096:1107	the residues of Thr576 and Thr577	1096:1128	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	11	62	theme	better	1806:1811	arg1	understanding					1813:1825	a better understanding	1804:1825	a better understanding of the roles O-glycosylation plays in the processing and functions of APP	1804:1899	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	8	63	theme	truncated	1391:1399	arg1	O-glycans					1401:1409	the truncated O-glycans	1387:1409	the truncated O-glycans on APP in HEK-293 T cell	1387:1434	Moreover, we also observed that TNF-α could upregulate the expression of APP and the truncated O-glycans on APP in HEK-293 T cell.
34229070	6	64	theme	Thr576	1112:1117	arg1	Thr577					1123:1128	Thr577	1123:1128	Thr577	1123:1128	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	6	64	theme	Thr576	1112:1117	arg1	Thr576					1112:1117	Thr576	1112:1117	Thr576	1112:1117	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	6	64	theme	Thr576	1112:1117	arg1	residues					1100:1107	the residues	1096:1107	the residues of Thr576 and Thr577	1096:1128	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	4	65	theme	TMMF	599:602	arg1	techniques					587:596	Multi-Fragmentation techniques	567:596	Multi-Fragmentation techniques (TMMF strategy)	567:612	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	4	65	theme	TMMF	599:602	arg1	strategy					604:611	TMMF strategy	599:611	TMMF strategy	599:611	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	8	66	from	expression	1365:1374	arg1	APP					1414:1416	APP	1414:1416	APP in HEK-293 T cell	1414:1434	Moreover, we also observed that TNF-α could upregulate the expression of APP and the truncated O-glycans on APP in HEK-293 T cell.
34229070	5	67	theme	APP	846:848	arg1	O-glycosylation					850:864	APP O-glycosylation	846:864	APP O-glycosylation	846:864	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	11	68	theme	roles	1834:1838	arg1	understanding					1813:1825	a better understanding	1804:1825	a better understanding of the roles O-glycosylation plays in the processing and functions of APP	1804:1899	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	5	69	gly	glycopeptides	748:760	arg2	glycopeptides					748:760	glycopeptides	748:760	glycopeptides with various O-glycosites and O-glycans	748:800	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	11	70	theme	O-glycan	1765:1772	arg1	structures					1774:1783	The accurate O-glycosites and O-glycan structures	1735:1783	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP	1714:1790	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	7	71	theme	region	1186:1191	arg1	beginning					1200:1208	the region nearby beginning	1182:1208	the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site	1182:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	1	72	theme	aberrant	144:151	arg1	step					262:265	a critical step	251:265	a critical step in the pathogenesis of Alzheimer's disease (AD)	251:313	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	72	theme	aberrant	144:151	arg1	processing					165:174	The aberrant proteolytic processing	140:174	The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain	140:246	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	5	73	with	glycopeptides	748:760	arg1	O-glycans					792:800	O-glycans	792:800	O-glycans	792:800	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	5	73	with	glycopeptides	748:760	arg1	O-glycosites					775:786	various O-glycosites	767:786	various O-glycosites	767:786	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	7	74	theme	O-glycans	1169:1177	arg1	cluster					1148:1154	a dense cluster	1140:1154	a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site	1140:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	9	75	theme	intact	1473:1478	arg1	strategy					1507:1514	an intact O-glycopeptide MS analysis strategy	1470:1514	an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1470:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	4	76	theme	APP695	675:680	arg1	profiling					662:670	O-glycosylation profiling	646:670	O-glycosylation profiling of APP695 expressed in HEK-293 T cells	646:709	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	7	77	from	cluster	1148:1154	arg1	beginning					1200:1208	the region nearby beginning	1182:1208	the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site	1182:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	78	theme	truncated	1159:1167	arg1	O-glycans					1169:1177	truncated O-glycans	1159:1177	truncated O-glycans	1159:1177	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	9	79	theme	MS	1495:1496	arg1	strategy					1507:1514	an intact O-glycopeptide MS analysis strategy	1470:1514	an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1470:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	0	80	theme	MS	116:117	arg1	strategy					119:126	targeted and multi-fragmentation MS strategy	83:126	targeted and multi-fragmentation MS strategy	83:126	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	6	81	theme	core	1061:1064	arg1	glycans					1068:1074	mono-/di-sialylated core 1 glycans	1041:1074	mono-/di-sialylated core 1 glycans	1041:1074	RESULTS A total of 14 O-glycosites were identified on three glycopeptides of APP, and at least four O-glycans including GalNAc (Tn antigen), core 1, and mono-/di-sialylated core 1 glycans were determinant at the residues of Thr576 and Thr577.
34229070	9	82	gly	O-glycopeptide	1480:1493	arg2	O-glycopeptide					1480:1493	O-glycopeptide	1480:1493	O-glycopeptide	1480:1493	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	2	83	gly	O-glycosylation	346:360	arg1	APP					365:367	APP	365:367	APP	365:367	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	9	84	dep	CONCLUSION	1437:1446	arg1	established					1458:1468	established	1458:1468	established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1458:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	5	85	theme	glycopeptides	748:760	arg1	abundance					735:743	relative abundance	726:743	relative abundance of glycopeptides with various O-glycosites and O-glycans	726:800	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	11	86	dep	roles	1834:1838	arg1	plays					1856:1860	plays	1856:1860	plays in the processing and functions of APP	1856:1899	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	9	87	theme	APP	1520:1522	arg1	identification					1539:1552	APP O-glycopeptide identification	1520:1552	APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1520:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	11	88	theme	GENERAL	1714:1720	arg1	SIGNIFICANCE					1722:1733	GENERAL SIGNIFICANCE	1714:1733	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP	1714:1790	GENERAL SIGNIFICANCE The accurate O-glycosites and O-glycan structures on APP may lead to a better understanding of the roles O-glycosylation plays in the processing and functions of APP.
34229070	2	89	theme	O-glycosylated	322:335	arg1	O-glycosylation					346:360	O-glycosylation	346:360	O-glycosylation of APP	346:367	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	2	89	theme	O-glycosylated	322:335	arg1	protein					337:343	an O-glycosylated protein	319:343	an O-glycosylated protein	319:343	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	0	90	theme	O-glycosylation	26:40	arg1	analysis					14:21	Comprehensive analysis	0:21	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP)	0:75	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	1	91	theme	critical	253:260	arg1	step					262:265	a critical step	251:265	a critical step in the pathogenesis of Alzheimer's disease (AD)	251:313	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	1	91	theme	critical	253:260	arg1	processing					165:174	The aberrant proteolytic processing	140:174	The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain	140:246	BACKGROUND The aberrant proteolytic processing of amyloid precursor protein (APP) into amyloid β peptide (Aβ) in brain is a critical step in the pathogenesis of Alzheimer's disease (AD).
34229070	0	92	theme	amyloid	45:51	arg1	APP					72:74	APP	72:74	APP	72:74	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	0	92	theme	amyloid	45:51	arg1	protein					63:69	amyloid precursor protein	45:69	amyloid precursor protein (APP)	45:75	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	9	93	theme	enhanced	1559:1566	arg1	efficiency					1582:1591	enhanced fragmentation efficiency	1559:1591	enhanced fragmentation efficiency	1559:1591	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	7	94	theme	sialylated	1245:1254	arg1	O-glycans					1256:1264	sialylated O-glycans	1245:1264	sialylated O-glycans on the region close to β-cleavage site	1245:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	9	95	gly	O-glycopeptide	1524:1537	arg2	O-glycopeptide					1524:1537	APP O-glycopeptide identification	1520:1552	APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity	1520:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	8	96	from	APP	1414:1416	arg1	cell					1431:1434	HEK-293 T cell	1421:1434	HEK-293 T cell	1421:1434	Moreover, we also observed that TNF-α could upregulate the expression of APP and the truncated O-glycans on APP in HEK-293 T cell.
34229070	0	97	theme	protein	63:69	arg1	O-glycosylation					26:40	O-glycosylation	26:40	O-glycosylation of amyloid precursor protein (APP)	26:75	Comprehensive analysis of O-glycosylation of amyloid precursor protein (APP) using targeted and multi-fragmentation MS strategy.
34229070	7	98	from	O-glycans	1256:1264	arg1	region					1273:1278	the region	1269:1278	the region close to β-cleavage site	1269:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	99	theme	abundance	1232:1240	arg1	beginning					1200:1208	the region nearby beginning	1182:1208	the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site	1182:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	2	100	theme	Aβ	400:401	arg1	generation					403:412	Aβ generation	400:412	Aβ generation	400:412	As an O-glycosylated protein, O-glycosylation of APP is considered to be related to Aβ generation.
34229070	10	101	theme	HEK-293 T	1698:1706	arg1	cell					1708:1711	HEK-293 T cell	1698:1711	HEK-293 T cell	1698:1711	These results provide a comprehensive O-glycosylation map of APP expressed in HEK-293 T cell.
34229070	9	102	theme	detection	1597:1605	arg1	sensitivity					1607:1617	detection sensitivity	1597:1617	detection sensitivity	1597:1617	CONCLUSION Our study established an intact O-glycopeptide MS analysis strategy for APP O-glycopeptide identification with enhanced fragmentation efficiency and detection sensitivity.
34229070	4	103	theme	Multi-Fragmentation	567:585	arg1	techniques					587:596	Multi-Fragmentation techniques	567:596	Multi-Fragmentation techniques (TMMF strategy)	567:612	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	4	103	theme	Multi-Fragmentation	567:585	arg1	strategy					604:611	TMMF strategy	599:611	TMMF strategy	599:611	METHODS We developed a Targeted MS approach with Multi-Fragmentation techniques (TMMF strategy), and successfully characterized O-glycosylation profiling of APP695 expressed in HEK-293 T cells.
34229070	5	104	gly	O-glycosites	775:786	arg2	O-glycosites					775:786	various O-glycosites	767:786	various O-glycosites	767:786	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	3	105	theme	comprehensive	426:438	arg1	analysis					440:447	comprehensive analysis	426:447	comprehensive analysis of APP O-glycosylation	426:470	Therefore, comprehensive analysis of APP O-glycosylation is important for understanding its functions.
34229070	5	106	theme	O-glycosylation	850:864	arg1	alteration					832:841	the alteration	828:841	the alteration of APP O-glycosylation upon TNF-α treatment	828:885	We calculated relative abundance of glycopeptides with various O-glycosites and O-glycans, and further investigated the alteration of APP O-glycosylation upon TNF-α treatment.
34229070	7	107	theme	E2	1213:1214	arg1	domain					1216:1221	E2 domain	1213:1221	E2 domain	1213:1221	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	107	theme	E2	1213:1214	arg1	O-glycans					1256:1264	sialylated O-glycans	1245:1264	sialylated O-glycans on the region close to β-cleavage site	1245:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	7	108	theme	β-cleavage	1289:1298	arg1	site					1300:1303	β-cleavage site	1289:1303	β-cleavage site	1289:1303	We found a dense cluster of truncated O-glycans on the region nearby beginning of E2 domain and high abundance of sialylated O-glycans on the region close to β-cleavage site.
34229070	8	109	theme	APP	1379:1381	arg1	O-glycans					1401:1409	the truncated O-glycans	1387:1409	the truncated O-glycans on APP in HEK-293 T cell	1387:1434	Moreover, we also observed that TNF-α could upregulate the expression of APP and the truncated O-glycans on APP in HEK-293 T cell.
34229070	8	109	theme	APP	1379:1381	arg1	expression					1365:1374	the expression	1361:1374	the expression of APP	1361:1381	Moreover, we also observed that TNF-α could upregulate the expression of APP and the truncated O-glycans on APP in HEK-293 T cell.
31913371	9	0	theme	mass	1654:1657	arg1	spectrometry					1659:1670	tandem mass spectrometry	1647:1670	tandem mass spectrometry	1647:1670	In parallel, the structure of the identified glycans was determined by ion mobility spectrometry coupled with tandem mass spectrometry.
31913371	6	1	from	concentrations	1008:1021	arg1	2.1					995:997	2.1	995:997	2.1	995:997	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	4	2	from	fluids	812:817	arg1	purification					783:794	immunoaffinity purification	768:794	immunoaffinity purification from biological fluids	768:817	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	7	3	dep	μg	1295:1296	arg1	3.1					1283:1285	3.1	1283:1285	3.1	1283:1285	The sensitivity and linearity of the method were suitable for serum analysis and the LOQ was calculated to be 3.1 and 4.4 μg mL-1 for transferrin (TFN) and trastuzumab (TRA), respectively.
31913371	7	3	dep	μg	1295:1296	arg1	4.4					1291:1293	4.4	1291:1293	4.4	1291:1293	The sensitivity and linearity of the method were suitable for serum analysis and the LOQ was calculated to be 3.1 and 4.4 μg mL-1 for transferrin (TFN) and trastuzumab (TRA), respectively.
31913371	8	4	theme	reference	1519:1527	arg1	levels					1529:1534	blood reference levels	1513:1534	blood reference levels	1513:1534	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	2	5	gly	glycoproteins	308:320	arg1	glycoproteins					308:320	glycoproteins	308:320	glycoproteins	308:320	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	8	6	theme	human	1411:1415	arg1	samples					1423:1429	five healthy human serum samples	1398:1429	five healthy human serum samples	1398:1429	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	11	7	theme	quality	1905:1911	arg1	control					1913:1919	the quality control	1901:1919	the quality control of large batches of biopharmaceuticals	1901:1958	This method should be useful for clinical laboratories and for the quality control of large batches of biopharmaceuticals.
31913371	6	8	from	concentrations	1040:1053	arg1	%					1030:1030	7.9%	1027:1030	7.9% (at low concentrations)	1027:1054	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	8	from	concentrations	1040:1053	arg1	precision					1082:1090	inter-day precision	1072:1090	inter-day precision	1072:1090	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	8	from	concentrations	1040:1053	arg1	intra-					1061:1066	intra-	1061:1066	intra-	1061:1066	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	8	9	theme	blood	1513:1517	arg1	levels					1529:1534	blood reference levels	1513:1534	blood reference levels	1513:1534	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	6	10	theme	method	937:942	arg1	%					1156:1156	3.2 and 8.2%	1145:1156	3.2 and 8.2%	1145:1156	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	10	theme	method	937:942	arg1	accuracy					921:928	The accuracy	917:928	The accuracy	917:928	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	1	11	gly	glycoproteins	200:212	arg1	glycoproteins					200:212	glycoproteins	200:212	glycoproteins	200:212	Glycosylation influences the structure and functionality of glycoproteins, and is regulated by genetic and environmental factors.
31913371	10	12	theme	samples	1819:1825	arg1	handling					1798:1805	the handling	1794:1805	the handling of up to 12 samples	1794:1825	No chromatographic separation was required and sample preparation was performed in a semi-automatic manner, facilitating the handling of up to 12 samples at a time.
31913371	2	13	theme	glycans	297:303	arg1	abundance					284:292	abundance	284:292	abundance	284:292	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	2	13	theme	glycans	297:303	arg1	types					274:278	types	274:278	types	274:278	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	11	14	theme	large	1924:1928	arg1	batches					1930:1936	large batches	1924:1936	large batches of biopharmaceuticals	1924:1958	This method should be useful for clinical laboratories and for the quality control of large batches of biopharmaceuticals.
31913371	4	15	theme	immunoaffinity	768:781	arg1	purification					783:794	immunoaffinity purification	768:794	immunoaffinity purification from biological fluids	768:817	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	3	16	theme	biomarkers	550:559	arg1	discovery					531:539	the discovery	527:539	the discovery of novel biomarkers	527:559	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	6	17	dep	expressed	945:953	arg1	expressed					1093:1101	expressed	1093:1101	expressed as relative standard deviation (RSD)	1093:1138	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	17	dep	expressed	945:953	arg1	ranged					983:988	ranged	983:988	ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision	983:1090	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	4	18	theme	glycoforms	722:731	arg1	quantification					704:717	quantification	704:717	quantification	704:717	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	4	18	theme	glycoforms	722:731	arg1	identification					685:698	identification	685:698	identification	685:698	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	5	19	theme	serum	860:864	arg1	transferrin					866:876	serum transferrin	860:876	serum transferrin	860:876	The method was validated and applied to serum transferrin and the biopharmaceutical trastuzumab.
31913371	4	20	theme	biological	801:810	arg1	fluids					812:817	biological fluids	801:817	biological fluids	801:817	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	7	21	dep	mL-1	1298:1301	arg1	μg					1295:1296	μg	1295:1296	μg	1295:1296	The sensitivity and linearity of the method were suitable for serum analysis and the LOQ was calculated to be 3.1 and 4.4 μg mL-1 for transferrin (TFN) and trastuzumab (TRA), respectively.
31913371	2	22	theme	neurodegenerative	392:408	arg1	disorders					410:418	neurodegenerative disorders	392:418	neurodegenerative disorders	392:418	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	0	23	theme	glycan	98:103	arg1	analysis					105:112	glycan analysis	98:112	glycan analysis using ion mobility-MS/MS	98:137	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	3	24	gly	glycoprotein	618:629	arg1	glycoprotein					618:629	glycoprotein biopharmaceuticals	618:648	glycoprotein biopharmaceuticals	618:648	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	10	25	theme	chromatographic	1676:1690	arg1	separation					1692:1701	No chromatographic separation	1673:1701	No chromatographic separation	1673:1701	No chromatographic separation was required and sample preparation was performed in a semi-automatic manner, facilitating the handling of up to 12 samples at a time.
31913371	7	26	dep	sensitivity	1177:1187	arg1	The					1173:1175	The	1173:1175	The	1173:1175	The sensitivity and linearity of the method were suitable for serum analysis and the LOQ was calculated to be 3.1 and 4.4 μg mL-1 for transferrin (TFN) and trastuzumab (TRA), respectively.
31913371	8	27	theme	serum	1417:1421	arg1	samples					1423:1429	five healthy human serum samples	1398:1429	five healthy human serum samples	1398:1429	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	2	28	dep	types	274:278	arg1	The					270:272	The	270:272	The	270:272	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	0	29	theme	N-Glycosylation	0:14	arg1	profiling					16:24	N-Glycosylation profiling	0:24	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.	0:138	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	9	30	theme	identified	1571:1580	arg1	glycans					1582:1588	the identified glycans	1567:1588	the identified glycans	1567:1588	In parallel, the structure of the identified glycans was determined by ion mobility spectrometry coupled with tandem mass spectrometry.
31913371	8	31	from	samples	1423:1429	arg1	application					1366:1376	Its application	1362:1376	Its application to transferrin from five healthy human serum samples	1362:1429	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	1	32	dep	structure	169:177	arg1	the					165:167	the	165:167	the	165:167	Glycosylation influences the structure and functionality of glycoproteins, and is regulated by genetic and environmental factors.
31913371	1	33	theme	glycoproteins	200:212	arg1	functionality					183:195	functionality	183:195	functionality	183:195	Glycosylation influences the structure and functionality of glycoproteins, and is regulated by genetic and environmental factors.
31913371	1	33	theme	glycoproteins	200:212	arg1	structure					169:177	structure	169:177	structure	169:177	Glycosylation influences the structure and functionality of glycoproteins, and is regulated by genetic and environmental factors.
31913371	0	34	theme	intact	29:34	arg1	proteins					43:50	intact target proteins	29:50	intact target proteins	29:50	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	4	35	theme	intact	745:750	arg1	proteins					752:759	intact proteins	745:759	intact proteins	745:759	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	0	36	theme	ion	120:122	arg1	mobility-MS/MS					124:137	ion mobility-MS/MS	120:137	ion mobility-MS/MS	120:137	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	6	37	theme	standard	1115:1122	arg1	deviation					1124:1132	relative standard deviation	1106:1132	relative standard deviation (RSD)	1106:1138	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	37	theme	standard	1115:1122	arg1	RSD					1135:1137	RSD	1135:1137	RSD	1135:1137	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	8	38	with	agreement	1498:1506	arg1	levels					1529:1534	blood reference levels	1513:1534	blood reference levels	1513:1534	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	3	39	theme	prime	571:575	arg1	importance					577:586	prime importance	571:586	prime importance	571:586	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	4	40	dep	identification	685:698	arg1	the					681:683	the	681:683	the	681:683	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	4	41	attach	present	660:666	arg2	we					657:658	we	657:658	we	657:658	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	4	41	attach	present	660:666	arg1	proteins					752:759	intact proteins	745:759	intact proteins	745:759	Here, we present a method for the identification and quantification of glycoforms directly on intact proteins, after immunoaffinity purification from biological fluids.
31913371	6	42	theme	relative	1106:1113	arg1	deviation					1124:1132	relative standard deviation	1106:1132	relative standard deviation (RSD)	1106:1138	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	42	theme	relative	1106:1113	arg1	RSD					1135:1137	RSD	1135:1137	RSD	1135:1137	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	2	43	from	types	274:278	arg1	glycoproteins					308:320	glycoproteins	308:320	glycoproteins	308:320	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	3	44	theme	protein	472:478	arg1	function					480:487	protein function	472:487	protein function	472:487	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	0	45	theme	proteins	43:50	arg1	profiling					16:24	N-Glycosylation profiling	0:24	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.	0:138	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	10	46	theme	sample	1720:1725	arg1	preparation					1727:1737	sample preparation	1720:1737	sample preparation	1720:1737	No chromatographic separation was required and sample preparation was performed in a semi-automatic manner, facilitating the handling of up to 12 samples at a time.
31913371	3	47	theme	crucial	432:438	arg1	role					440:443	the crucial role	428:443	the crucial role glycans play in modulating protein function	428:487	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	0	48	theme	target	36:41	arg1	proteins					43:50	intact target proteins	29:50	intact target proteins	29:50	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	11	49	theme	biopharmaceuticals	1941:1958	arg1	batches					1930:1936	large batches	1924:1936	large batches of biopharmaceuticals	1924:1958	This method should be useful for clinical laboratories and for the quality control of large batches of biopharmaceuticals.
31913371	10	50	theme	semi-automatic	1758:1771	arg1	manner					1773:1778	a semi-automatic manner	1756:1778	a semi-automatic manner	1756:1778	No chromatographic separation was required and sample preparation was performed in a semi-automatic manner, facilitating the handling of up to 12 samples at a time.
31913371	7	51	theme	serum	1235:1239	arg1	analysis					1241:1248	serum analysis	1235:1248	serum analysis	1235:1248	The sensitivity and linearity of the method were suitable for serum analysis and the LOQ was calculated to be 3.1 and 4.4 μg mL-1 for transferrin (TFN) and trastuzumab (TRA), respectively.
31913371	0	52	theme	high-resolution	55:69	arg1	MS					90:91	MS	90:91	MS	90:91	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	0	52	theme	high-resolution	55:69	arg1	spectrometry					76:87	high-resolution mass spectrometry	55:87	high-resolution mass spectrometry (MS)	55:92	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	8	53	theme	mg	1476:1477	arg1	mL-1					1479:1482	3.17 mg mL-1	1471:1482	3.17 mg mL-1	1471:1482	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	9	54	theme	ion	1608:1610	arg1	spectrometry					1621:1632	ion mobility spectrometry	1608:1632	ion mobility spectrometry coupled with tandem mass spectrometry	1608:1670	In parallel, the structure of the identified glycans was determined by ion mobility spectrometry coupled with tandem mass spectrometry.
31913371	9	55	theme	tandem	1647:1652	arg1	spectrometry					1659:1670	tandem mass spectrometry	1647:1670	tandem mass spectrometry	1647:1670	In parallel, the structure of the identified glycans was determined by ion mobility spectrometry coupled with tandem mass spectrometry.
31913371	3	56	dep	role	440:443	arg1	play					453:456	play	453:456	play in modulating protein function	453:487	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	3	57	theme	glycosylation	490:502	arg1	analysis					504:511	glycosylation analysis	490:511	glycosylation analysis	490:511	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	8	58	theme	healthy	1403:1409	arg1	samples					1423:1429	five healthy human serum samples	1398:1429	five healthy human serum samples	1398:1429	Its application to transferrin from five healthy human serum samples yielded concentrations between 1.61 and 3.17 mg mL-1, which are in agreement with blood reference levels.
31913371	6	59	theme	relative	962:969	arg1	error					971:975	the relative error	958:975	the relative error (RE)	958:980	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	59	theme	relative	962:969	arg1	RE					978:979	RE	978:979	RE	978:979	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	6	60	theme	low	1036:1038	arg1	concentrations					1040:1053	low concentrations	1036:1053	low concentrations	1036:1053	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	2	61	from	abundance	284:292	arg1	glycoproteins					308:320	glycoproteins	308:320	glycoproteins	308:320	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	9	62	theme	glycans	1582:1588	arg1	structure					1554:1562	the structure	1550:1562	the structure of the identified glycans	1550:1588	In parallel, the structure of the identified glycans was determined by ion mobility spectrometry coupled with tandem mass spectrometry.
31913371	9	63	theme	mobility	1612:1619	arg1	spectrometry					1621:1632	ion mobility spectrometry	1608:1632	ion mobility spectrometry coupled with tandem mass spectrometry	1608:1670	In parallel, the structure of the identified glycans was determined by ion mobility spectrometry coupled with tandem mass spectrometry.
31913371	11	64	theme	clinical	1871:1878	arg1	laboratories					1880:1891	clinical laboratories	1871:1891	clinical laboratories	1871:1891	This method should be useful for clinical laboratories and for the quality control of large batches of biopharmaceuticals.
31913371	3	65	theme	glycoprotein	618:629	arg1	biopharmaceuticals					631:648	glycoprotein biopharmaceuticals	618:648	glycoprotein biopharmaceuticals	618:648	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	10	66	dep	12	1816:1817	arg1	to					1813:1814	to	1813:1814	to	1813:1814	No chromatographic separation was required and sample preparation was performed in a semi-automatic manner, facilitating the handling of up to 12 samples at a time.
31913371	11	67	theme	batches	1930:1936	arg1	control					1913:1919	the quality control	1901:1919	the quality control of large batches of biopharmaceuticals	1901:1958	This method should be useful for clinical laboratories and for the quality control of large batches of biopharmaceuticals.
31913371	6	68	dep	accuracy	921:928	arg1	expressed					945:953	expressed	945:953	expressed as the relative error (RE)	945:980	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	3	69	theme	biopharmaceuticals	631:648	arg1	quality					607:613	the quality	603:613	the quality of glycoprotein biopharmaceuticals	603:648	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	7	70	theme	method	1210:1215	arg1	linearity					1193:1201	linearity	1193:1201	linearity	1193:1201	The sensitivity and linearity of the method were suitable for serum analysis and the LOQ was calculated to be 3.1 and 4.4 μg mL-1 for transferrin (TFN) and trastuzumab (TRA), respectively.
31913371	7	70	theme	method	1210:1215	arg1	sensitivity					1177:1187	sensitivity	1177:1187	sensitivity	1177:1187	The sensitivity and linearity of the method were suitable for serum analysis and the LOQ was calculated to be 3.1 and 4.4 μg mL-1 for transferrin (TFN) and trastuzumab (TRA), respectively.
31913371	2	71	from	glycans	297:303	arg1	glycoproteins					308:320	glycoproteins	308:320	glycoproteins	308:320	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	1	72	theme	genetic	235:241	arg1	factors					261:267	genetic and environmental factors	235:267	genetic and environmental factors	235:267	Glycosylation influences the structure and functionality of glycoproteins, and is regulated by genetic and environmental factors.
31913371	6	73	theme	inter-day	1072:1080	arg1	precision					1082:1090	inter-day precision	1072:1090	inter-day precision	1072:1090	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	5	74	theme	biopharmaceutical	886:902	arg1	trastuzumab					904:914	the biopharmaceutical trastuzumab	882:914	the biopharmaceutical trastuzumab	882:914	The method was validated and applied to serum transferrin and the biopharmaceutical trastuzumab.
31913371	0	75	theme	mass	71:74	arg1	MS					90:91	MS	90:91	MS	90:91	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	0	75	theme	mass	71:74	arg1	spectrometry					76:87	high-resolution mass spectrometry	55:87	high-resolution mass spectrometry (MS)	55:92	N-Glycosylation profiling of intact target proteins by high-resolution mass spectrometry (MS) and glycan analysis using ion mobility-MS/MS.
31913371	3	76	theme	novel	544:548	arg1	biomarkers					550:559	novel biomarkers	544:559	novel biomarkers	544:559	Due to the crucial role glycans play in modulating protein function, glycosylation analysis could lead to the discovery of novel biomarkers and is of prime importance in controlling the quality of glycoprotein biopharmaceuticals.
31913371	6	77	theme	high	1003:1006	arg1	concentrations					1008:1021	high concentrations	1003:1021	high concentrations	1003:1021	The accuracy of the method, expressed as the relative error (RE), ranged from 2.1 (at high concentrations) to 7.9% (at low concentrations), and intra- and inter-day precision, expressed as relative standard deviation (RSD), was 3.2 and 8.2%, respectively.
31913371	2	78	from	glycoproteins	308:320	arg1	abundance					284:292	abundance	284:292	abundance	284:292	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	2	78	from	glycoproteins	308:320	arg1	types					274:278	types	274:278	types	274:278	The types and abundance of glycans on glycoproteins can vary due to diseases such as cancer, inflammation, autoimmune and neurodegenerative disorders.
31913371	1	79	theme	environmental	247:259	arg1	factors					261:267	genetic and environmental factors	235:267	genetic and environmental factors	235:267	Glycosylation influences the structure and functionality of glycoproteins, and is regulated by genetic and environmental factors.
34213308	6	0	theme	recombinant	927:937	arg1	glycosylation					972:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
34213308	3	1	theme	infectious	515:524	arg1	virus					526:530	infectious virus	515:530	infectious virus	515:530	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	3	2	from	virus	526:530	arg1	protein					502:508	S protein	500:508	S protein from infectious virus, cultured in Vero cells	500:554	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	1	3	theme	vaccines	97:104	arg1	design					87:92	the design	83:92	the design of vaccines	83:104	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	4	4	theme	protein	733:739	arg1	structure					741:749	protein structure	733:749	protein structure	733:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	6	5	theme	glycosylation	1033:1045	arg1	signatures					1013:1022	signatures	1013:1022	signatures of viral glycosylation	1013:1045	These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
34213308	1	6	theme	central	66:72	arg1	tenet					74:78	A central tenet	64:78	A central tenet in the design of vaccines	64:104	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	1	6	theme	central	66:72	arg1	display					113:119	the display	109:119	the display of native-like antigens in the elicitation of protective immunity	109:185	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	3	7	theme	S	500:500	arg1	protein					502:508	S protein	500:508	S protein from infectious virus, cultured in Vero cells	500:554	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	3	8	gly	glycosylation	387:399	arg1	proteins					433:440	recombinant SARS-CoV-2 spike proteins	404:440	recombinant SARS-CoV-2 spike proteins from five different laboratories	404:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	2	9	theme	potential	263:271	arg1	source					273:278	a potential source	261:278	a potential source of heterogeneity	261:295	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	2	9	theme	potential	263:271	arg1	abundance					192:200	The abundance	188:200	The abundance of N-linked glycans across the SARS-CoV-2 spike protein	188:256	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	3	10	theme	proteins	433:440	arg1	glycosylation					387:399	the glycosylation	383:399	the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories	383:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	5	11	theme	enzymatic	863:871	arg1	processing					873:882	enzymatic processing	863:882	enzymatic processing of the glycans	863:897	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	3	12	theme	recombinant	404:414	arg1	proteins					433:440	recombinant SARS-CoV-2 spike proteins	404:440	recombinant SARS-CoV-2 spike proteins from five different laboratories	404:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	3	13	theme	SARS-CoV-2	416:425	arg1	proteins					433:440	recombinant SARS-CoV-2 spike proteins	404:440	recombinant SARS-CoV-2 spike proteins from five different laboratories	404:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	1	14	from	display	113:119	arg1	elicitation					152:162	the elicitation	148:162	the elicitation of protective immunity	148:185	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	3	15	theme	Vero	545:548	arg1	cells					550:554	Vero cells	545:554	Vero cells	545:554	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	3	16	theme	different	452:460	arg1	laboratories					462:473	five different laboratories	447:473	five different laboratories	447:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	0	17	theme	Steric	14:19	arg1	Control					21:27	Site-Specific Steric Control	0:27	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation	0:61	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
34213308	3	18	from	glycosylation	387:399	arg1	laboratories					462:473	five different laboratories	447:473	five different laboratories	447:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	2	19	theme	many	307:310	arg1	candidates					330:339	the many different vaccine candidates	303:339	the many different vaccine candidates under investigation	303:359	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	1	20	theme	protective	167:176	arg1	immunity					178:185	protective immunity	167:185	protective immunity	167:185	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	0	21	theme	Site-Specific	0:12	arg1	Control					21:27	Site-Specific Steric Control	0:27	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation	0:61	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
34213308	6	22	theme	viral	1027:1031	arg1	glycosylation					1033:1045	viral glycosylation	1027:1045	viral glycosylation	1027:1045	These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
34213308	4	23	theme	sensitive	711:719	arg1	stalling					659:666	site-specific stalling	645:666	site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure	645:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	4	23	theme	sensitive	711:719	arg1	reporter					721:728	a highly sensitive reporter	702:728	a highly sensitive reporter of protein structure	702:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	1	24	theme	immunity	178:185	arg1	elicitation					152:162	the elicitation	148:162	the elicitation of protective immunity	148:185	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	5	25	theme	steric	832:837	arg1	restrictions					839:850	steric restrictions	832:850	steric restrictions that shape enzymatic processing of the glycans	832:897	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	2	26	theme	heterogeneity	283:295	arg1	source					273:278	a potential source	261:278	a potential source of heterogeneity	261:295	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	2	26	theme	heterogeneity	283:295	arg1	abundance					192:200	The abundance	188:200	The abundance of N-linked glycans across the SARS-CoV-2 spike protein	188:256	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	5	27	theme	restrictions	839:850	arg1	model					823:827	a model	821:827	a model of steric restrictions that shape enzymatic processing of the glycans	821:897	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	0	28	theme	Spike	43:47	arg1	Glycosylation					49:61	SARS-CoV-2 Spike Glycosylation	32:61	SARS-CoV-2 Spike Glycosylation	32:61	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
34213308	4	29	theme	glycan	671:676	arg1	maturation					678:687	glycan maturation	671:687	glycan maturation	671:687	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	0	30	theme	SARS-CoV-2	32:41	arg1	Glycosylation					49:61	SARS-CoV-2 Spike Glycosylation	32:61	SARS-CoV-2 Spike Glycosylation	32:61	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
34213308	3	31	theme	spike	427:431	arg1	proteins					433:440	recombinant SARS-CoV-2 spike proteins	404:440	recombinant SARS-CoV-2 spike proteins from five different laboratories	404:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	3	32	from	laboratories	462:473	arg1	proteins					433:440	recombinant SARS-CoV-2 spike proteins	404:440	recombinant SARS-CoV-2 spike proteins from five different laboratories	404:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	3	32	from	laboratories	462:473	arg1	glycosylation					387:399	the glycosylation	383:399	the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories	383:473	Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells.
34213308	6	33	theme	SARS-CoV-2	951:960	arg1	glycosylation					972:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
34213308	5	34	theme	glycosylated	794:805	arg1	spike					807:811	a fully glycosylated spike	786:811	a fully glycosylated spike	786:811	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	5	35	theme	glycans	891:897	arg1	processing					873:882	enzymatic processing	863:882	enzymatic processing of the glycans	863:897	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	5	36	theme	spike	807:811	arg1	simulations					771:781	Molecular dynamics simulations	752:781	Molecular dynamics simulations of a fully glycosylated spike	752:811	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	2	37	theme	glycans	214:220	arg1	source					273:278	a potential source	261:278	a potential source of heterogeneity	261:295	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	2	37	theme	glycans	214:220	arg1	abundance					192:200	The abundance	188:200	The abundance of N-linked glycans across the SARS-CoV-2 spike protein	188:256	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	0	38	theme	Glycosylation	49:61	arg1	Control					21:27	Site-Specific Steric Control	0:27	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation	0:61	Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation.
34213308	6	39	theme	immunogen	962:970	arg1	glycosylation					972:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
34213308	2	40	theme	N-linked	205:212	arg1	glycans					214:220	N-linked glycans	205:220	N-linked glycans	205:220	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	5	41	gly	glycosylated	794:805	arg1	spike					807:811	a fully glycosylated spike	786:811	a fully glycosylated spike	786:811	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	4	42	theme	maturation	678:687	arg1	stalling					659:666	site-specific stalling	645:666	site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure	645:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	4	42	theme	maturation	678:687	arg1	reporter					721:728	a highly sensitive reporter	702:728	a highly sensitive reporter of protein structure	702:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	2	43	theme	vaccine	322:328	arg1	candidates					330:339	the many different vaccine candidates	303:339	the many different vaccine candidates under investigation	303:359	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	4	44	theme	structure	741:749	arg1	stalling					659:666	site-specific stalling	645:666	site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure	645:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	4	44	theme	structure	741:749	arg1	reporter					721:728	a highly sensitive reporter	702:728	a highly sensitive reporter of protein structure	702:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	2	45	theme	different	312:320	arg1	candidates					330:339	the many different vaccine candidates	303:339	the many different vaccine candidates under investigation	303:359	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	2	46	link	N-linked	205:212	arg1	glycans					214:220	N-linked glycans	205:220	N-linked glycans	205:220	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	5	47	theme	Molecular	752:760	arg1	simulations					771:781	Molecular dynamics simulations	752:781	Molecular dynamics simulations of a fully glycosylated spike	752:811	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	2	48	theme	spike	244:248	arg1	protein					250:256	the SARS-CoV-2 spike protein	229:256	the SARS-CoV-2 spike protein	229:256	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	1	49	theme	native-like	124:134	arg1	antigens					136:143	native-like antigens	124:143	native-like antigens	124:143	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	4	50	theme	site-specific	645:657	arg1	stalling					659:666	site-specific stalling	645:666	site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure	645:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	4	50	theme	site-specific	645:657	arg1	reporter					721:728	a highly sensitive reporter	702:728	a highly sensitive reporter of protein structure	702:749	We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure.
34213308	5	51	theme	dynamics	762:769	arg1	simulations					771:781	Molecular dynamics simulations	752:781	Molecular dynamics simulations of a fully glycosylated spike	752:811	Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans.
34213308	6	52	theme	spike-based	939:949	arg1	glycosylation					972:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	recombinant spike-based SARS-CoV-2 immunogen glycosylation	927:984	These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
34213308	2	53	theme	SARS-CoV-2	233:242	arg1	protein					250:256	the SARS-CoV-2 spike protein	229:256	the SARS-CoV-2 spike protein	229:256	The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation.
34213308	1	54	theme	antigens	136:143	arg1	display					113:119	the display	109:119	the display of native-like antigens in the elicitation of protective immunity	109:185	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	1	54	theme	antigens	136:143	arg1	tenet					74:78	A central tenet	64:78	A central tenet in the design of vaccines	64:104	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
34213308	1	55	from	tenet	74:78	arg1	design					87:92	the design	83:92	the design of vaccines	83:104	A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity.
32699088	7	0	theme	glycan	1310:1315	arg1	additions					1317:1325	glycan additions	1310:1325	glycan additions	1310:1325	It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions.
32699088	10	1	link	N-linked	1894:1901	arg1	sites					1917:1921	N-linked glycosylation sites	1894:1921	N-linked glycosylation sites on the NA enzymatic head domain	1894:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	2	theme	NA	1930:1931	arg1	domain					1948:1953	the NA enzymatic head domain	1926:1953	the NA enzymatic head domain	1926:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	11	3	link	N-linked	2117:2124	arg1	sites					2140:2144	the N-linked glycosylation sites	2113:2144	the N-linked glycosylation sites on the NA head domain	2113:2166	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	7	4	theme	domain	1260:1265	arg1	glycans					1267:1273	the head domain glycans	1251:1273	the head domain glycans	1251:1273	It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions.
32699088	9	5	theme	antigen	1755:1761	arg1	epitopes					1763:1770	surface antigen epitopes	1747:1770	surface antigen epitopes	1747:1770	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	8	6	theme	NA	1465:1466	arg1	amount					1468:1473	the NA amount	1461:1473	the NA amount in virions.IMPORTANCE N-linked glycans	1461:1512	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	10	7	theme	A	1808:1808	arg1	IAV					1817:1819	IAV	1817:1819	IAV	1817:1819	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	7	theme	A	1808:1808	arg1	virus					1810:1814	influenza A virus	1798:1814	the influenza A virus (IAV) surface antigen neuraminidase (NA or N)	1794:1860	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	2	8	theme	A	273:273	arg1	IAV					282:284	IAV	282:284	IAV	282:284	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	8	theme	A	273:273	arg1	virus					275:279	the influenza A virus	259:279	the influenza A virus (IAV)	259:285	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	11	9	theme	virion	2182:2187	arg1	incorporation					2189:2201	virion incorporation	2182:2201	virion incorporation	2182:2201	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	6	10	theme	NA	1098:1099	arg1	domain					1106:1111	the NA head domain	1094:1111	the NA head domain	1094:1111	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	0	11	theme	N-Linked	0:7	arg1	Sites					16:20	N-Linked Glycan Sites	0:20	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain	0:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	1	12	theme	secretory	177:185	arg1	folding					195:201	secretory protein folding	177:201	secretory protein folding	177:201	N-linked glycans commonly contribute to secretory protein folding, sorting, and signaling.
32699088	13	13	from	changes	2417:2423	arg1	sites					2451:2455	N-linked glycosylation sites	2428:2455	N-linked glycosylation sites	2428:2455	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	10	14	theme	head	1943:1946	arg1	domain					1948:1953	the NA enzymatic head domain	1926:1953	the NA enzymatic head domain	1926:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	3	15	gly	glycosylation	517:529	arg2	sites					531:535	three N-linked glycosylation sites	502:535	three N-linked glycosylation sites	502:535	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	3	15	gly	glycosylation	517:529	arg2	three					502:506	three	502:506	three	502:506	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	6	16	link	N-linked	1062:1069	arg1	sites					1085:1089	the N-linked glycosylation sites	1058:1089	the N-linked glycosylation sites on the NA head domain	1058:1111	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	13	17	theme	surface	2493:2499	arg1	antigens					2501:2508	viral surface antigens	2487:2508	viral surface antigens	2487:2508	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	11	18	from	sites	2140:2144	arg1	domain					2161:2166	the NA head domain	2149:2166	the NA head domain	2149:2166	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	8	19	link	N-linked	1395:1402	arg1	sites					1418:1422	N-linked glycosylation sites	1395:1422	N-linked glycosylation sites	1395:1422	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	3	20	theme	head	476:479	arg1	domain					481:486	the NA head domain	469:486	the NA head domain of H1N1 IAVs	469:499	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	3	20	theme	head	476:479	arg1	IAVs					496:499	H1N1 IAVs	491:499	H1N1 IAVs	491:499	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	8	21	theme	reticulum	1584:1592	arg1	lumen					1594:1598	the endoplasmic reticulum lumen	1568:1598	the endoplasmic reticulum lumen	1568:1598	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	4	22	theme	H1N1	810:813	arg1	IAV					815:817	the 2009 pandemic H1N1 IAV	792:817	the 2009 pandemic H1N1 IAV	792:817	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	7	23	theme	N1	1218:1219	arg1	stability					1221:1229	N1 stability	1218:1229	N1 stability	1218:1229	It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions.
32699088	5	24	gly	glycosylation	944:956	arg2	sites					958:962	head glycosylation sites	939:962	head glycosylation sites	939:962	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	12	25	dep	suggesting	2300:2309	arg1	accommodating					2322:2334	accommodating	2322:2334	accommodating	2322:2334	It also revealed that the head domain glycans affect N1 stability more than N2, suggesting N2 is more accommodating to glycan additions.
32699088	6	26	theme	N-linked	1062:1069	arg1	sites					1085:1089	the N-linked glycosylation sites	1058:1089	the N-linked glycosylation sites on the NA head domain	1058:1111	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	10	27	theme	antigen	1830:1836	arg1	neuraminidase					1838:1850	the influenza A virus (IAV) surface antigen neuraminidase	1794:1850	the influenza A virus (IAV) surface antigen neuraminidase (NA or N)	1794:1860	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	5	28	theme	human	895:899	arg1	origin					911:916	human and swine origin	895:916	human and swine origin	895:916	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	3	29	theme	IAVs	496:499	arg1	domain					481:486	the NA head domain	469:486	the NA head domain of H1N1 IAVs	469:499	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	3	29	theme	IAVs	496:499	arg1	IAVs					496:499	H1N1 IAVs	491:499	H1N1 IAVs	491:499	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	6	30	theme	efficient	1130:1138	arg1	incorporation					1147:1159	efficient virion incorporation	1130:1159	efficient virion incorporation	1130:1159	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	5	31	theme	swine	905:909	arg1	origin					911:916	human and swine origin	895:916	human and swine origin	895:916	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	10	32	theme	origin	2012:2017	arg1	subtype					1970:1976	IAV subtype	1966:1976	IAV subtype (H1N1 versus H3N2)	1966:1995	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	32	theme	origin	2012:2017	arg1	species					2001:2007	species	2001:2007	species of origin	2001:2017	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	0	33	theme	Neuraminidase	47:59	arg1	Domain					66:71	the Influenza A Virus Neuraminidase Head Domain	25:71	the Influenza A Virus Neuraminidase Head Domain	25:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	3	34	theme	glycosylation	517:529	arg1	sites					531:535	three N-linked glycosylation sites	502:535	three N-linked glycosylation sites	502:535	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	13	35	theme	N-linked	2428:2435	arg1	sites					2451:2455	N-linked glycosylation sites	2428:2455	N-linked glycosylation sites	2428:2455	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	0	36	from	Sites	16:20	arg1	Domain					66:71	the Influenza A Virus Neuraminidase Head Domain	25:71	the Influenza A Virus Neuraminidase Head Domain	25:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	9	37	dep	promoting	1616:1624	arg1	addition					1604:1611	addition	1604:1611	addition	1604:1611	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	13	38	theme	viral	2487:2491	arg1	antigens					2501:2508	viral surface antigens	2487:2508	viral surface antigens	2487:2508	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	11	39	gly	glycosylation	2126:2138	arg2	sites					2140:2144	the N-linked glycosylation sites	2113:2144	the N-linked glycosylation sites on the NA head domain	2113:2166	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	13	40	theme	virions	2514:2520	arg1	properties					2473:2482	other properties	2467:2482	other properties of viral surface antigens and virions	2467:2520	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	10	41	dep	neuraminidase	1838:1850	arg1	N					1859:1859	N	1859:1859	N	1859:1859	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	41	dep	neuraminidase	1838:1850	arg1	NA					1853:1854	NA	1853:1854	NA	1853:1854	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	4	42	theme	human	653:657	arg1	origin					659:664	human origin	653:664	human origin	653:664	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	4	43	theme	swine	831:835	arg1	origin					837:842	Eurasian swine origin	822:842	Eurasian swine origin	822:842	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	10	44	gly	glycosylation	1903:1915	arg2	sites					1917:1921	N-linked glycosylation sites	1894:1921	N-linked glycosylation sites on the NA enzymatic head domain	1894:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	45	from	sites	1917:1921	arg1	domain					1948:1953	the NA enzymatic head domain	1926:1953	the NA enzymatic head domain	1926:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	0	46	theme	Efficient	90:98	arg1	Incorporation					106:118	Efficient Viral Incorporation	90:118	Efficient Viral Incorporation	90:118	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	5	47	theme	glycosylation	944:956	arg1	sites					958:962	head glycosylation sites	939:962	head glycosylation sites	939:962	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	2	48	dep	hemagglutinin	383:395	arg1	HA					398:399	HA	398:399	HA	398:399	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	48	dep	hemagglutinin	383:395	arg1	H					404:404	H	404:404	H	404:404	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	11	49	theme	NA	2153:2154	arg1	domain					2161:2166	the NA head domain	2149:2166	the NA head domain	2149:2166	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	3	50	link	N-linked	508:515	arg1	sites					531:535	three N-linked glycosylation sites	502:535	three N-linked glycosylation sites	502:535	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	13	51	theme	other	2467:2471	arg1	properties					2473:2482	other properties	2467:2482	other properties of viral surface antigens and virions	2467:2520	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	4	52	gly	glycosylation	692:704	arg2	sites					706:710	head glycosylation sites	687:710	head glycosylation sites	687:710	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	9	53	theme	enveloped	1656:1664	arg1	viruses					1666:1672	enveloped viruses	1656:1672	enveloped viruses	1656:1672	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	10	54	from	domain	1948:1953	arg1	conservation					1878:1889	the conservation	1874:1889	the conservation of N-linked glycosylation sites on the NA enzymatic head domain	1874:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	13	55	gly	glycosylation	2437:2449	arg2	sites					2451:2455	N-linked glycosylation sites	2428:2455	N-linked glycosylation sites	2428:2455	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	1	56	link	N-linked	137:144	arg1	glycans					146:152	N-linked glycans	137:152	N-linked glycans	137:152	N-linked glycans commonly contribute to secretory protein folding, sorting, and signaling.
32699088	4	57	theme	glycosylation	692:704	arg1	sites					706:710	head glycosylation sites	687:710	head glycosylation sites	687:710	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	5	58	theme	H3N2	882:885	arg1	IAVs					887:890	H3N2 IAVs	882:890	H3N2 IAVs	882:890	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	10	59	dep	subtype	1970:1976	arg1	H3N2					1991:1994	H3N2	1991:1994	H3N2	1991:1994	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	59	dep	subtype	1970:1976	arg1	H1N1					1979:1982	H1N1	1979:1982	H1N1	1979:1982	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	12	60	theme	head	2246:2249	arg1	glycans					2258:2264	the head domain glycans	2242:2264	the head domain glycans	2242:2264	It also revealed that the head domain glycans affect N1 stability more than N2, suggesting N2 is more accommodating to glycan additions.
32699088	2	61	dep	antigens	374:381	arg1	hemagglutinin					383:395	hemagglutinin	383:395	hemagglutinin (HA or H)	383:405	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	61	dep	antigens	374:381	arg1	antigens					374:381	the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N)	362:433	the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N)	362:433	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	61	dep	antigens	374:381	arg1	neuraminidase					411:423	neuraminidase	411:423	neuraminidase (NA or N)	411:433	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	0	62	theme	A	39:39	arg1	Domain					66:71	the Influenza A Virus Neuraminidase Head Domain	25:71	the Influenza A Virus Neuraminidase Head Domain	25:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	2	63	from	epitopes	350:357	arg1	hemagglutinin					383:395	hemagglutinin	383:395	hemagglutinin (HA or H)	383:405	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	63	from	epitopes	350:357	arg1	neuraminidase					411:423	neuraminidase	411:423	neuraminidase (NA or N)	411:433	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	63	from	epitopes	350:357	arg1	antigens					374:381	the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N)	362:433	the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N)	362:433	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	9	64	theme	oligosaccharide	1699:1713	arg1	structures					1715:1724	these large oligosaccharide structures	1687:1724	these large oligosaccharide structures	1687:1724	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	8	65	theme	glycosylation	1404:1416	arg1	sites					1418:1422	N-linked glycosylation sites	1395:1422	N-linked glycosylation sites	1395:1422	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	2	66	theme	N-linked	294:301	arg1	glycans					303:309	large N-linked glycans	288:309	large N-linked glycans	288:309	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	7	67	theme	head	1255:1258	arg1	glycans					1267:1273	the head domain glycans	1251:1273	the head domain glycans	1251:1273	It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions.
32699088	5	68	theme	variable	858:865	arg1	sites					867:871	variable sites	858:871	variable sites	858:871	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	10	69	theme	N-linked	1894:1901	arg1	sites					1917:1921	N-linked glycosylation sites	1894:1921	N-linked glycosylation sites on the NA enzymatic head domain	1894:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	6	70	contain	carrying	1013:1020	arg2	mutants					1032:1038	N1 and N2 mutants	1022:1038	N1 and N2 mutants	1022:1038	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	6	70	contain	carrying	1013:1020	arg1	IAVs					1008:1011	IAVs	1008:1011	IAVs carrying N1 and N2 mutants	1008:1038	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	11	71	theme	N-linked	2117:2124	arg1	sites					2140:2144	the N-linked glycosylation sites	2113:2144	the N-linked glycosylation sites on the NA head domain	2113:2166	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	3	72	theme	Sequence	436:443	arg1	analysis					445:452	Sequence analysis	436:452	Sequence analysis	436:452	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	8	73	theme	virions.IMPORTANCE	1478:1495	arg1	glycans					1506:1512	virions.IMPORTANCE N-linked glycans	1478:1512	virions.IMPORTANCE N-linked glycans	1478:1512	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	10	74	theme	enzymatic	1933:1941	arg1	domain					1948:1953	the NA enzymatic head domain	1926:1953	the NA enzymatic head domain	1926:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	8	75	theme	NA	1434:1435	arg1	stability					1447:1455	NA enzymatic stability	1434:1455	NA enzymatic stability	1434:1455	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	10	76	theme	Sequence	1773:1780	arg1	analyses					1782:1789	Sequence analyses	1773:1789	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N)	1773:1860	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	9	77	theme	surface	1747:1753	arg1	epitopes					1763:1770	surface antigen epitopes	1747:1770	surface antigen epitopes	1747:1770	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	6	78	gly	glycosylation	1071:1083	arg2	sites					1085:1089	the N-linked glycosylation sites	1058:1089	the N-linked glycosylation sites on the NA head domain	1058:1111	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	3	79	theme	H3N2	590:593	arg1	IAVs					595:598	H3N2 IAVs	590:598	H3N2 IAVs	590:598	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	6	80	theme	N1	1022:1023	arg1	mutants					1032:1038	N1 and N2 mutants	1022:1038	N1 and N2 mutants	1022:1038	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	10	81	theme	influenza	1798:1806	arg1	IAV					1817:1819	IAV	1817:1819	IAV	1817:1819	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	81	theme	influenza	1798:1806	arg1	virus					1810:1814	influenza A virus	1798:1814	the influenza A virus (IAV) surface antigen neuraminidase (NA or N)	1794:1860	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	6	82	theme	head	1101:1104	arg1	domain					1106:1111	the NA head domain	1094:1111	the NA head domain	1094:1111	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	2	83	theme	influenza	263:271	arg1	IAV					282:284	IAV	282:284	IAV	282:284	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	83	theme	influenza	263:271	arg1	virus					275:279	the influenza A virus	259:279	the influenza A virus (IAV)	259:285	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	8	84	theme	secretory	1533:1541	arg1	proteins					1543:1550	secretory proteins	1533:1550	secretory proteins	1533:1550	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	10	85	theme	IAV	1966:1968	arg1	subtype					1970:1976	IAV subtype	1966:1976	IAV subtype (H1N1 versus H3N2)	1966:1995	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	6	86	theme	IAVs	1008:1011	arg1	Analysis					996:1003	Analysis	996:1003	Analysis of IAVs carrying N1 and N2 mutants	996:1038	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	11	87	theme	Experimental	2077:2088	arg1	analyses					2090:2097	Experimental analyses	2077:2097	Experimental analyses	2077:2097	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	1	88	theme	protein	187:193	arg1	folding					195:201	secretory protein folding	177:201	secretory protein folding	177:201	N-linked glycans commonly contribute to secretory protein folding, sorting, and signaling.
32699088	11	89	theme	glycosylation	2126:2138	arg1	sites					2140:2144	the N-linked glycosylation sites	2113:2144	the N-linked glycosylation sites on the NA head domain	2113:2166	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	3	90	theme	NA	473:474	arg1	domain					481:486	the NA head domain	469:486	the NA head domain of H1N1 IAVs	469:499	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	3	90	theme	NA	473:474	arg1	IAVs					496:499	H1N1 IAVs	491:499	H1N1 IAVs	491:499	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	13	91	theme	antigens	2501:2508	arg1	properties					2473:2482	other properties	2467:2482	other properties of viral surface antigens and virions	2467:2520	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	10	92	theme	virus	1810:1814	arg1	neuraminidase					1838:1850	the influenza A virus (IAV) surface antigen neuraminidase	1794:1850	the influenza A virus (IAV) surface antigen neuraminidase (NA or N)	1794:1860	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	2	93	theme	enveloped	232:240	arg1	virus					275:279	the influenza A virus	259:279	the influenza A virus (IAV)	259:285	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	93	theme	enveloped	232:240	arg1	viruses					242:248	enveloped viruses	232:248	enveloped viruses	232:248	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	8	94	theme	endoplasmic	1572:1582	arg1	reticulum					1584:1592	the endoplasmic reticulum	1568:1592	the endoplasmic reticulum lumen	1568:1598	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	10	95	theme	sites	1917:1921	arg1	conservation					1878:1889	the conservation	1874:1889	the conservation of N-linked glycosylation sites on the NA enzymatic head domain	1874:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	4	96	theme	pandemic	801:808	arg1	IAV					815:817	the 2009 pandemic H1N1 IAV	792:817	the 2009 pandemic H1N1 IAV	792:817	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	6	97	theme	glycosylation	1071:1083	arg1	sites					1085:1089	the N-linked glycosylation sites	1058:1089	the N-linked glycosylation sites on the NA head domain	1058:1111	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	12	98	theme	domain	2251:2256	arg1	glycans					2258:2264	the head domain glycans	2242:2264	the head domain glycans	2242:2264	It also revealed that the head domain glycans affect N1 stability more than N2, suggesting N2 is more accommodating to glycan additions.
32699088	10	99	theme	neuraminidase	1838:1850	arg1	analyses					1782:1789	Sequence analyses	1773:1789	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N)	1773:1860	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	3	100	theme	H1N1	491:494	arg1	IAVs					496:499	H1N1 IAVs	491:499	H1N1 IAVs	491:499	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	4	101	theme	Variable	601:608	arg1	sites					610:614	Variable sites	601:614	Variable sites	601:614	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	10	102	theme	surface	1822:1828	arg1	neuraminidase					1838:1850	the influenza A virus (IAV) surface antigen neuraminidase	1794:1850	the influenza A virus (IAV) surface antigen neuraminidase (NA or N)	1794:1860	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	6	103	theme	virion	1140:1145	arg1	incorporation					1147:1159	efficient virion incorporation	1130:1159	efficient virion incorporation	1130:1159	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	13	104	link	N-linked	2428:2435	arg1	sites					2451:2455	N-linked glycosylation sites	2428:2455	N-linked glycosylation sites	2428:2455	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	6	105	from	sites	1085:1089	arg1	domain					1106:1111	the NA head domain	1094:1111	the NA head domain	1094:1111	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	0	106	theme	Head	61:64	arg1	Domain					66:71	the Influenza A Virus Neuraminidase Head Domain	25:71	the Influenza A Virus Neuraminidase Head Domain	25:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	5	107	theme	origin	911:916	arg1	IAVs					887:890	H3N2 IAVs	882:890	H3N2 IAVs	882:890	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	3	108	theme	N-linked	508:515	arg1	sites					531:535	three N-linked glycosylation sites	502:535	three N-linked glycosylation sites	502:535	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	1	109	theme	N-linked	137:144	arg1	glycans					146:152	N-linked glycans	137:152	N-linked glycans	137:152	N-linked glycans commonly contribute to secretory protein folding, sorting, and signaling.
32699088	11	110	theme	head	2156:2159	arg1	domain					2161:2166	the NA head domain	2149:2166	the NA head domain	2149:2166	Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication.
32699088	4	111	theme	origin	837:842	arg1	introduction					776:787	the introduction	772:787	the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin	772:842	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	6	112	theme	N2	1029:1030	arg1	mutants					1032:1038	N1 and N2 mutants	1022:1038	N1 and N2 mutants	1022:1038	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	10	113	contain	possessing	2044:2053	arg1	IAVs					2039:2042	human-derived IAVs	2025:2042	human-derived IAVs possessing the most variability	2025:2074	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	113	contain	possessing	2044:2053	arg2	variability					2064:2074	the most variability	2055:2074	the most variability	2055:2074	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	8	114	link	N-linked	1497:1504	arg1	glycans					1506:1512	virions.IMPORTANCE N-linked glycans	1478:1512	virions.IMPORTANCE N-linked glycans	1478:1512	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	13	115	theme	glycosylation	2437:2449	arg1	sites					2451:2455	N-linked glycosylation sites	2428:2455	N-linked glycosylation sites	2428:2455	These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
32699088	2	116	dep	neuraminidase	411:423	arg1	N					432:432	N	432:432	N	432:432	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	116	dep	neuraminidase	411:423	arg1	NA					426:427	NA	426:427	NA	426:427	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	4	117	theme	IAV	815:817	arg1	introduction					776:787	the introduction	772:787	the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin	772:842	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	10	118	theme	human-derived	2025:2037	arg1	IAVs					2039:2042	human-derived IAVs	2025:2042	human-derived IAVs possessing the most variability	2025:2074	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	0	119	theme	Viral	100:104	arg1	Incorporation					106:118	Efficient Viral Incorporation	90:118	Efficient Viral Incorporation	90:118	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	5	120	theme	head	939:942	arg1	sites					958:962	head glycosylation sites	939:962	head glycosylation sites	939:962	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	4	121	theme	Eurasian	822:829	arg1	origin					837:842	Eurasian swine origin	822:842	Eurasian swine origin	822:842	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	4	122	theme	origin	659:664	arg1	IAVs					645:648	H1N1 IAVs	640:648	H1N1 IAVs	640:648	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	9	123	theme	secretory	1626:1634	arg1	maturation					1644:1653	secretory protein maturation	1626:1653	secretory protein maturation	1626:1653	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	0	124	theme	Glycan	9:14	arg1	Sites					16:20	N-Linked Glycan Sites	0:20	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain	0:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	5	125	theme	sites	958:962	arg1	number					929:934	the number	925:934	the number of head glycosylation sites	925:962	In contrast, variable sites exist in H3N2 IAVs of human and swine origin, where the number of head glycosylation sites has mainly increased over time.
32699088	12	126	theme	N1	2273:2274	arg1	stability					2276:2284	N1 stability	2273:2284	N1 stability	2273:2284	It also revealed that the head domain glycans affect N1 stability more than N2, suggesting N2 is more accommodating to glycan additions.
32699088	10	127	theme	most	2059:2062	arg1	variability					2064:2074	the most variability	2055:2074	the most variability	2055:2074	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	6	128	from	replication	1165:1175	arg1	eggs					1190:1193	eggs	1190:1193	eggs	1190:1193	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	6	128	from	replication	1165:1175	arg1	cells					1180:1184	cells	1180:1184	cells	1180:1184	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	8	129	gly	glycosylation	1404:1416	arg2	sites					1418:1422	N-linked glycosylation sites	1395:1422	N-linked glycosylation sites	1395:1422	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	4	130	theme	H1N1	640:643	arg1	IAVs					645:648	H1N1 IAVs	640:648	H1N1 IAVs	640:648	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	2	131	theme	surface	366:372	arg1	hemagglutinin					383:395	hemagglutinin	383:395	hemagglutinin (HA or H)	383:405	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	131	theme	surface	366:372	arg1	neuraminidase					411:423	neuraminidase	411:423	neuraminidase (NA or N)	411:433	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	2	131	theme	surface	366:372	arg1	antigens					374:381	the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N)	362:433	the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N)	362:433	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	0	132	theme	Influenza	29:37	arg1	Domain					66:71	the Influenza A Virus Neuraminidase Head Domain	25:71	the Influenza A Virus Neuraminidase Head Domain	25:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	8	133	theme	N-linked	1395:1402	arg1	sites					1418:1422	N-linked glycosylation sites	1395:1422	N-linked glycosylation sites	1395:1422	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	4	134	theme	head	687:690	arg1	sites					706:710	head glycosylation sites	687:710	head glycosylation sites	687:710	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	9	135	theme	protein	1636:1642	arg1	maturation					1644:1653	secretory protein maturation	1626:1653	secretory protein maturation	1626:1653	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	0	136	theme	Virus	41:45	arg1	Domain					66:71	the Influenza A Virus Neuraminidase Head Domain	25:71	the Influenza A Virus Neuraminidase Head Domain	25:71	N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication.
32699088	7	137	dep	suggesting	1276:1285	arg1	amenable					1298:1305	amenable	1298:1305	amenable	1298:1305	It also revealed that N1 stability is more affected by the head domain glycans, suggesting N2 is more amenable to glycan additions.
32699088	9	138	theme	large	1693:1697	arg1	structures					1715:1724	these large oligosaccharide structures	1687:1724	these large oligosaccharide structures	1687:1724	In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes.
32699088	4	139	theme	sites	706:710	arg1	number					677:682	the number	673:682	the number of head glycosylation sites	673:710	Variable sites are almost exclusive to H1N1 IAVs of human origin, where the number of head glycosylation sites first increased over time and then decreased with and after the introduction of the 2009 pandemic H1N1 IAV of Eurasian swine origin.
32699088	6	140	from	incorporation	1147:1159	arg1	eggs					1190:1193	eggs	1190:1193	eggs	1190:1193	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	6	140	from	incorporation	1147:1159	arg1	cells					1180:1184	cells	1180:1184	cells	1180:1184	Analysis of IAVs carrying N1 and N2 mutants demonstrated that the N-linked glycosylation sites on the NA head domain are required for efficient virion incorporation and replication in cells and eggs.
32699088	10	141	from	conservation	1878:1889	arg1	domain					1948:1953	the NA enzymatic head domain	1926:1953	the NA enzymatic head domain	1926:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	10	142	theme	glycosylation	1903:1915	arg1	sites					1917:1921	N-linked glycosylation sites	1894:1921	N-linked glycosylation sites on the NA enzymatic head domain	1894:1953	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
32699088	8	143	from	amount	1468:1473	arg1	glycans					1506:1512	virions.IMPORTANCE N-linked glycans	1478:1512	virions.IMPORTANCE N-linked glycans	1478:1512	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	3	144	theme	fourth	562:567	arg1	site					569:572	a fourth site	560:572	a fourth site	560:572	Sequence analysis showed that in the NA head domain of H1N1 IAVs, three N-linked glycosylation sites are conserved and that a fourth site is conserved in H3N2 IAVs.
32699088	2	145	theme	large	288:292	arg1	glycans					303:309	large N-linked glycans	288:309	large N-linked glycans	288:309	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	8	146	theme	N-linked	1497:1504	arg1	glycans					1506:1512	virions.IMPORTANCE N-linked glycans	1478:1512	virions.IMPORTANCE N-linked glycans	1478:1512	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	12	147	theme	glycan	2339:2344	arg1	additions					2346:2354	glycan additions	2339:2354	glycan additions	2339:2354	It also revealed that the head domain glycans affect N1 stability more than N2, suggesting N2 is more accommodating to glycan additions.
32699088	8	148	theme	enzymatic	1437:1445	arg1	stability					1447:1455	NA enzymatic stability	1434:1455	NA enzymatic stability	1434:1455	Together, these results indicate that in addition to antigenicity, N-linked glycosylation sites can alter NA enzymatic stability and the NA amount in virions.IMPORTANCE N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen.
32699088	2	149	link	N-linked	294:301	arg1	glycans					303:309	large N-linked glycans	288:309	large N-linked glycans	288:309	For enveloped viruses, such as the influenza A virus (IAV), large N-linked glycans can also be added to prevent access to epitopes on the surface antigens hemagglutinin (HA or H) and neuraminidase (NA or N).
32699088	10	150	link	human-derived	2025:2037	arg1	IAVs					2039:2042	human-derived IAVs	2025:2042	human-derived IAVs possessing the most variability	2025:2074	Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability.
34401920	0	0	link	N-linked	18:25	arg1	Glycoproteins					27:39	N-linked Glycoproteins	18:39	N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry	18:122	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	3	1	theme	high	530:533	arg1	abundance					535:543	high abundance	530:543	high abundance	530:543	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	7	2	theme	N-Linked	869:876	arg1	glycosylation					878:890	N-Linked glycosylation	869:890	N-Linked glycosylation	869:890	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	6	3	gly	glycosylation	833:845	arg2	one					829:831	one	829:831	one	829:831	82 N-linked glycoproteins with at least one glycosylation site were identified.
34401920	6	3	gly	glycosylation	833:845	arg2	site					847:850	at least one glycosylation site	820:850	at least one glycosylation site	820:850	82 N-linked glycoproteins with at least one glycosylation site were identified.
34401920	6	4	link	N-linked	792:799	arg1	glycoproteins					801:813	82 N-linked glycoproteins	789:813	82 N-linked glycoproteins with at least one glycosylation site	789:850	82 N-linked glycoproteins with at least one glycosylation site were identified.
34401920	8	5	located	found	1070:1074	arg2	structures					1059:1068	The N-glycan structures	1046:1068	The N-glycan structures found in serum glycoproteins	1046:1097	The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%).
34401920	8	5	located	found	1070:1074	arg1	glycoproteins					1085:1097	serum glycoproteins	1079:1097	serum glycoproteins	1079:1097	The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%).
34401920	8	5	located	found	1070:1074	arg2	Man2FucGlcNAc2					1111:1124	Man2FucGlcNAc2	1111:1124	Man2FucGlcNAc2 (67.9%)	1111:1132	The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%).
34401920	4	6	theme	A	645:645	arg1	fractions					663:671	the Con A lectin-enriched fractions	637:671	the Con A lectin-enriched fractions	637:671	LC-MS/MS identified 149 larval and 303 pupal serum proteins in the Con A lectin-enriched fractions.
34401920	6	7	theme	N-linked	792:799	arg1	glycoproteins					801:813	82 N-linked glycoproteins	789:813	82 N-linked glycoproteins with at least one glycosylation site	789:850	82 N-linked glycoproteins with at least one glycosylation site were identified.
34401920	1	8	theme	modifications	184:196	arg1	one					142:144	one	142:144	one	142:144	Glycosylation is one of the most common post-translational modifications to occur during protein biosynthesis, but remains poorly understood in insects.
34401920	1	8	theme	modifications	184:196	arg1	modifications					184:196	the most common post-translational modifications	149:196	the most common post-translational modifications	149:196	Glycosylation is one of the most common post-translational modifications to occur during protein biosynthesis, but remains poorly understood in insects.
34401920	7	9	from	position	995:1002	arg1	Thr					962:964	Thr	962:964	Thr	962:964	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	7	9	from	position	995:1002	arg1	Ser					954:956	Ser	954:956	Ser	954:956	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	7	9	from	position	995:1002	arg1	proportions					939:949	the proportions	935:949	the proportions of Ser and Thr glycosylation at the hydroxy position	935:1002	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	6	10	with	glycoproteins	801:813	arg1	site					847:850	at least one glycosylation site	820:850	at least one glycosylation site	820:850	82 N-linked glycoproteins with at least one glycosylation site were identified.
34401920	11	11	theme	glycosylation	1537:1549	arg1	function					1516:1523	the function	1512:1523	the function of N-linked glycosylation in metabolism, immunity, and metamorphosis	1512:1592	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	5	12	theme	many	700:703	arg1	proteins					711:718	many serum proteins	700:718	many serum proteins	700:718	GO analysis revealed that many serum proteins were involved in the proteolysis and carbohydrate metabolic process.
34401920	1	13	theme	protein	214:220	arg1	biosynthesis					222:233	protein biosynthesis	214:233	protein biosynthesis	214:233	Glycosylation is one of the most common post-translational modifications to occur during protein biosynthesis, but remains poorly understood in insects.
34401920	11	14	from	metamorphosis	1580:1592	arg1	understanding					1495:1507	the understanding	1491:1507	the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis	1491:1592	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	3	15	gly	glycoproteins	559:571	arg1	glycoproteins					559:571	putative glycoproteins	550:571	putative glycoproteins	550:571	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	9	16	gly	glycosylation	1279:1291	arg1	detail					1309:1314	detail	1309:1314	detail	1309:1314	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	0	17	theme	Con	65:67	arg1	Chromatography					87:100	Con A Lectin Affinity Chromatography	65:100	Con A Lectin Affinity Chromatography	65:100	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	9	18	theme	Con	1259:1261	arg1	lectin					1265:1270	Con A lectin	1259:1270	Con A lectin	1259:1270	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	11	19	from	function	1516:1523	arg1	immunity					1566:1573	immunity	1566:1573	immunity	1566:1573	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	11	19	from	function	1516:1523	arg1	metamorphosis					1580:1592	metamorphosis	1580:1592	metamorphosis	1580:1592	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	11	19	from	function	1516:1523	arg1	metabolism					1554:1563	metabolism	1554:1563	metabolism	1554:1563	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	0	20	theme	Lectin	71:76	arg1	Chromatography					87:100	Con A Lectin Affinity Chromatography	65:100	Con A Lectin Affinity Chromatography	65:100	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	1	21	theme	common	158:163	arg1	modifications					184:196	the most common post-translational modifications	149:196	the most common post-translational modifications	149:196	Glycosylation is one of the most common post-translational modifications to occur during protein biosynthesis, but remains poorly understood in insects.
34401920	5	22	dep	analysis	677:684	arg1	GO					674:675	GO	674:675	GO	674:675	GO analysis revealed that many serum proteins were involved in the proteolysis and carbohydrate metabolic process.
34401920	0	23	from	Identification	0:13	arg1	Serum					53:57	Silkworm Serum	44:57	Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry	44:122	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	7	24	dep	Ser	954:956	arg1	glycosylation					966:978	glycosylation	966:978	glycosylation	966:978	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	0	25	from	Serum	53:57	arg1	Identification					0:13	Identification	0:13	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.	0:123	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	2	26	theme	instar	387:392	arg1	stage					401:405	the fifth instar larval stage	377:405	the fifth instar larval stage	377:405	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	0	27	theme	Mass	106:109	arg1	Spectrometry					111:122	Mass Spectrometry	106:122	Mass Spectrometry	106:122	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	2	28	theme	pupal	424:428	arg1	stage					430:434	the pupal stage	420:434	the pupal stage	420:434	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	8	29	gly	glycoproteins	1085:1097	arg1	glycoproteins					1085:1097	serum glycoproteins	1079:1097	serum glycoproteins	1079:1097	The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%).
34401920	8	30	theme	N-glycan	1050:1057	arg1	Man2FucGlcNAc2					1111:1124	Man2FucGlcNAc2	1111:1124	Man2FucGlcNAc2 (67.9%)	1111:1132	The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%).
34401920	8	30	theme	N-glycan	1050:1057	arg1	structures					1059:1068	The N-glycan structures	1046:1068	The N-glycan structures found in serum glycoproteins	1046:1097	The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%).
34401920	0	31	theme	N-linked	18:25	arg1	Glycoproteins					27:39	N-linked Glycoproteins	18:39	N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry	18:122	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	2	32	theme	stage	401:405	arg1	stages					353:358	two silkworm developmental stages	326:358	two silkworm developmental stages	326:358	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	32	theme	stage	401:405	arg1	day					368:370	day 7	368:372	day 7 of the fifth instar larval stage	368:405	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	32	theme	stage	401:405	arg1	day					411:413	day 2	411:415	day 2 of the pupal stage	411:434	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	3	33	with	proteins	516:523	arg1	abundance					535:543	high abundance	530:543	high abundance	530:543	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	8	34	theme	serum	1079:1083	arg1	glycoproteins					1085:1097	serum glycoproteins	1079:1097	serum glycoproteins	1079:1097	The N-glycan structures found in serum glycoproteins were mainly Man2FucGlcNAc2 (67.9%).
34401920	3	35	theme	periodic	461:468	arg1	staining					482:489	periodic acid-Schiff staining	461:489	periodic acid-Schiff staining	461:489	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	10	36	theme	interacting	1391:1401	arg1	networks					1416:1423	three interacting glycoprotein networks	1385:1423	three interacting glycoprotein networks using the website STRING	1385:1448	Glycoside hydrases, serine proteases and serpins were found to form three interacting glycoprotein networks using the website STRING.
34401920	2	37	theme	silkworm	330:337	arg1	stages					353:358	two silkworm developmental stages	326:358	two silkworm developmental stages	326:358	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	37	theme	silkworm	330:337	arg1	day					368:370	day 7	368:372	day 7 of the fifth instar larval stage	368:405	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	37	theme	silkworm	330:337	arg1	day					411:413	day 2	411:415	day 2 of the pupal stage	411:434	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	6	38	theme	glycosylation	833:845	arg1	site					847:850	at least one glycosylation site	820:850	at least one glycosylation site	820:850	82 N-linked glycoproteins with at least one glycosylation site were identified.
34401920	4	39	theme	larval	598:603	arg1	proteins					625:632	149 larval and 303 pupal serum proteins	594:632	149 larval and 303 pupal serum proteins	594:632	LC-MS/MS identified 149 larval and 303 pupal serum proteins in the Con A lectin-enriched fractions.
34401920	10	40	theme	serine	1337:1342	arg1	proteases					1344:1352	serine proteases	1337:1352	serine proteases	1337:1352	Glycoside hydrases, serine proteases and serpins were found to form three interacting glycoprotein networks using the website STRING.
34401920	11	41	link	N-linked	1528:1535	arg1	glycosylation					1537:1549	N-linked glycosylation	1528:1549	N-linked glycosylation	1528:1549	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	5	42	theme	carbohydrate	757:768	arg1	process					780:786	the proteolysis and carbohydrate metabolic process	737:786	process	780:786	GO analysis revealed that many serum proteins were involved in the proteolysis and carbohydrate metabolic process.
34401920	3	43	theme	staining	482:489	arg1	Results					437:443	Results	437:443	Results of SDS-PAGE and periodic acid-Schiff staining	437:489	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	10	44	gly	glycoprotein	1403:1414	arg1	glycoprotein					1403:1414	three interacting glycoprotein networks	1385:1423	three interacting glycoprotein networks using the website STRING	1385:1448	Glycoside hydrases, serine proteases and serpins were found to form three interacting glycoprotein networks using the website STRING.
34401920	11	45	theme	N-linked	1528:1535	arg1	glycosylation					1537:1549	N-linked glycosylation	1528:1549	N-linked glycosylation	1528:1549	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	11	46	theme	function	1516:1523	arg1	understanding					1495:1507	the understanding	1491:1507	the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis	1491:1592	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	3	47	theme	serum	510:514	arg1	proteins					516:523	most serum proteins	505:523	most serum proteins with high abundance	505:543	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	1	48	theme	post-translational	165:182	arg1	modifications					184:196	the most common post-translational modifications	149:196	the most common post-translational modifications	149:196	Glycosylation is one of the most common post-translational modifications to occur during protein biosynthesis, but remains poorly understood in insects.
34401920	4	49	theme	Con	641:643	arg1	A					645:645	Con A	641:645	the Con A lectin-enriched fractions	637:671	LC-MS/MS identified 149 larval and 303 pupal serum proteins in the Con A lectin-enriched fractions.
34401920	5	50	theme	metabolic	770:778	arg1	process					780:786	the proteolysis and carbohydrate metabolic process	737:786	process	780:786	GO analysis revealed that many serum proteins were involved in the proteolysis and carbohydrate metabolic process.
34401920	9	51	theme	high	1192:1195	arg1	abundance					1197:1205	a relatively high abundance	1179:1205	a relatively high abundance	1179:1205	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	3	52	theme	putative	550:557	arg1	glycoproteins					559:571	putative glycoproteins	550:571	putative glycoproteins	550:571	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	4	53	theme	lectin-enriched	647:661	arg1	fractions					663:671	the Con A lectin-enriched fractions	637:671	the Con A lectin-enriched fractions	637:671	LC-MS/MS identified 149 larval and 303 pupal serum proteins in the Con A lectin-enriched fractions.
34401920	2	54	theme	serum	306:310	arg1	proteins					312:319	serum proteins	306:319	serum proteins	306:319	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	11	55	from	immunity	1566:1573	arg1	understanding					1495:1507	the understanding	1491:1507	the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis	1491:1592	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	4	56	theme	serum	619:623	arg1	proteins					625:632	149 larval and 303 pupal serum proteins	594:632	149 larval and 303 pupal serum proteins	594:632	LC-MS/MS identified 149 larval and 303 pupal serum proteins in the Con A lectin-enriched fractions.
34401920	2	57	theme	developmental	339:351	arg1	stages					353:358	two silkworm developmental stages	326:358	two silkworm developmental stages	326:358	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	57	theme	developmental	339:351	arg1	day					368:370	day 7	368:372	day 7 of the fifth instar larval stage	368:405	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	57	theme	developmental	339:351	arg1	day					411:413	day 2	411:415	day 2 of the pupal stage	411:434	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	5	58	theme	serum	705:709	arg1	proteins					711:718	many serum proteins	700:718	many serum proteins	700:718	GO analysis revealed that many serum proteins were involved in the proteolysis and carbohydrate metabolic process.
34401920	6	59	gly	glycoproteins	801:813	arg1	glycoproteins					801:813	82 N-linked glycoproteins	789:813	82 N-linked glycoproteins with at least one glycosylation site	789:850	82 N-linked glycoproteins with at least one glycosylation site were identified.
34401920	7	60	from	proportions	939:949	arg1	position					995:1002	the hydroxy position	983:1002	the hydroxy position	983:1002	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	11	61	theme	important	1471:1479	arg1	clues					1481:1485	important clues	1471:1485	important clues	1471:1485	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	11	62	from	metabolism	1554:1563	arg1	understanding					1495:1507	the understanding	1491:1507	the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis	1491:1592	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	3	63	theme	SDS-PAGE	448:455	arg1	Results					437:443	Results	437:443	Results of SDS-PAGE and periodic acid-Schiff staining	437:489	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	0	64	theme	A	69:69	arg1	Chromatography					87:100	Con A Lectin Affinity Chromatography	65:100	Con A Lectin Affinity Chromatography	65:100	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	0	65	from	Glycoproteins	27:39	arg1	Serum					53:57	Silkworm Serum	44:57	Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry	44:122	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	0	66	theme	Affinity	78:85	arg1	Chromatography					87:100	Con A Lectin Affinity Chromatography	65:100	Con A Lectin Affinity Chromatography	65:100	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	9	67	theme	A	1263:1263	arg1	lectin					1265:1270	Con A lectin	1259:1270	Con A lectin	1259:1270	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	7	68	theme	hydroxy	987:993	arg1	position					995:1002	the hydroxy position	983:1002	the hydroxy position	983:1002	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	7	69	gly	glycosylation	878:890	arg2	sequon					908:913	the sequon	904:913	the sequon	904:913	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	10	70	theme	glycoprotein	1403:1414	arg1	networks					1416:1423	three interacting glycoprotein networks	1385:1423	three interacting glycoprotein networks using the website STRING	1385:1448	Glycoside hydrases, serine proteases and serpins were found to form three interacting glycoprotein networks using the website STRING.
34401920	7	71	theme	Thr	962:964	arg1	proportions					939:949	the proportions	935:949	the proportions of Ser and Thr glycosylation at the hydroxy position	935:1002	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	11	72	from	understanding	1495:1507	arg1	immunity					1566:1573	immunity	1566:1573	immunity	1566:1573	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	11	72	from	understanding	1495:1507	arg1	metamorphosis					1580:1592	metamorphosis	1580:1592	metamorphosis	1580:1592	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	11	72	from	understanding	1495:1507	arg1	metabolism					1554:1563	metabolism	1554:1563	metabolism	1554:1563	This study provides important clues for the understanding of the function of N-linked glycosylation in metabolism, immunity, and metamorphosis.
34401920	2	73	theme	fifth	381:385	arg1	stage					401:405	the fifth instar larval stage	377:405	the fifth instar larval stage	377:405	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	7	74	theme	Ser	954:956	arg1	proportions					939:949	the proportions	935:949	the proportions of Ser and Thr glycosylation at the hydroxy position	935:1002	N-Linked glycosylation occurred at the sequon, Asn-X-Ser/Thr, and the proportions of Ser and Thr glycosylation at the hydroxy position were found 39.6% and 60.3%, respectively.
34401920	10	75	theme	website	1435:1441	arg1	STRING					1443:1448	the website STRING	1431:1448	the website STRING	1431:1448	Glycoside hydrases, serine proteases and serpins were found to form three interacting glycoprotein networks using the website STRING.
34401920	0	76	theme	Glycoproteins	27:39	arg1	Identification					0:13	Identification	0:13	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.	0:123	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	9	77	theme	storage	1141:1147	arg1	protein					1149:1155	storage protein 1	1141:1157	storage protein 1	1141:1157	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	0	78	theme	Silkworm	44:51	arg1	Serum					53:57	Silkworm Serum	44:57	Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry	44:122	Identification of N-linked Glycoproteins in Silkworm Serum Using Con A Lectin Affinity Chromatography and Mass Spectrometry.
34401920	10	79	theme	Glycoside	1317:1325	arg1	hydrases					1327:1334	Glycoside hydrases	1317:1334	Glycoside hydrases	1317:1334	Glycoside hydrases, serine proteases and serpins were found to form three interacting glycoprotein networks using the website STRING.
34401920	2	80	theme	larval	394:399	arg1	stage					401:405	the fifth instar larval stage	377:405	the fifth instar larval stage	377:405	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	81	theme	stage	430:434	arg1	stages					353:358	two silkworm developmental stages	326:358	two silkworm developmental stages	326:358	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	81	theme	stage	430:434	arg1	day					368:370	day 7	368:372	day 7 of the fifth instar larval stage	368:405	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	2	81	theme	stage	430:434	arg1	day					411:413	day 2	411:415	day 2 of the pupal stage	411:434	In this study, we collected serum proteins from two silkworm developmental stages, namely day 7 of the fifth instar larval stage and day 2 of the pupal stage.
34401920	3	82	theme	acid-Schiff	470:480	arg1	staining					482:489	periodic acid-Schiff staining	461:489	periodic acid-Schiff staining	461:489	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34401920	9	83	contain	had	1175:1177	arg2	abundance					1197:1205	a relatively high abundance	1179:1205	a relatively high abundance	1179:1205	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	9	83	contain	had	1175:1177	arg1	protein					1149:1155	storage protein 1	1141:1157	storage protein 1	1141:1157	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	9	83	contain	had	1175:1177	arg1	transferrin					1163:1173	transferrin	1163:1173	transferrin	1163:1173	Since storage protein 1 and transferrin had a relatively high abundance in the serum and could be significantly enriched by Con A lectin, their glycosylation was analyzed in detail.
34401920	4	84	theme	pupal	613:617	arg1	proteins					625:632	149 larval and 303 pupal serum proteins	594:632	149 larval and 303 pupal serum proteins	594:632	LC-MS/MS identified 149 larval and 303 pupal serum proteins in the Con A lectin-enriched fractions.
34401920	3	85	theme	most	505:508	arg1	proteins					516:523	most serum proteins	505:523	most serum proteins with high abundance	505:543	Results of SDS-PAGE and periodic acid-Schiff staining revealed that most serum proteins with high abundance were putative glycoproteins.
34343291	9	0	theme	allosteric	1303:1312	arg1	dynamics					1314:1321	long-range allosteric dynamics	1292:1321	long-range allosteric dynamics	1292:1321	These changes are accompanied by perturbations in glycan-protein interactions and perturbation of long-range allosteric dynamics.
34343291	0	1	from	changes	11:17	arg1	composition					29:39	glycan composition	22:39	glycan composition	22:39	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	7	2	theme	removal	1042:1048	arg1	result					1028:1033	a result	1026:1033	a result of the removal of sialic acid	1026:1063	We observed perturbations in L1 domain dynamics as a result of the removal of sialic acid.
34343291	7	2	theme	removal	1042:1048	arg1	perturbations					987:999	perturbations	987:999	perturbations in L1 domain dynamics	987:1021	We observed perturbations in L1 domain dynamics as a result of the removal of sialic acid.
34343291	1	3	theme	common	141:146	arg1	modifications					167:179	the most common post-translational modifications	132:179	the most common post-translational modifications in proteins	132:191	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	3	4	from	removal	496:502	arg1	N-glycans					533:541	N-glycans	533:541	N-glycans of insulin receptor (IR)	533:566	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	6	5	theme	L1	943:944	arg1	ectodomain					963:972	the IR ectodomain	956:972	the IR ectodomain	956:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	6	5	theme	L1	943:944	arg1	domain					946:951	leucine-rich repeat L1 domain	923:951	leucine-rich repeat L1 domain of the IR ectodomain	923:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	7	6	theme	domain	1007:1012	arg1	dynamics					1014:1021	L1 domain dynamics	1004:1021	L1 domain dynamics	1004:1021	We observed perturbations in L1 domain dynamics as a result of the removal of sialic acid.
34343291	6	7	theme	acid	873:876	arg1	removal					855:861	removal	855:861	removal of sialic acid	855:876	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	1	8	theme	post-translational	148:165	arg1	modifications					167:179	the most common post-translational modifications	132:179	the most common post-translational modifications in proteins	132:191	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	10	9	theme	glycan	1440:1445	arg1	composition					1447:1457	glycan composition	1440:1457	glycan composition	1440:1457	Our observations will further aid in understanding the role of sugars in maintaining homeostasis and how changes in glycan composition may lead to perturbations in homeostasis, ultimately leading to conditions such as insulin resistance.
34343291	6	10	theme	repeat	936:941	arg1	ectodomain					963:972	the IR ectodomain	956:972	the IR ectodomain	956:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	6	10	theme	repeat	936:941	arg1	domain					946:951	leucine-rich repeat L1 domain	923:951	leucine-rich repeat L1 domain of the IR ectodomain	923:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	0	11	from	Effects	0:6	arg1	composition					29:39	glycan composition	22:39	glycan composition	22:39	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	0	11	from	Effects	0:6	arg1	dynamics					57:64	glycoprotein dynamics	44:64	glycoprotein dynamics	44:64	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	10	12	theme	sugars	1387:1392	arg1	role					1379:1382	the role	1375:1382	the role of sugars	1375:1392	Our observations will further aid in understanding the role of sugars in maintaining homeostasis and how changes in glycan composition may lead to perturbations in homeostasis, ultimately leading to conditions such as insulin resistance.
34343291	3	13	theme	residues	519:526	arg1	removal					496:502	the removal	492:502	the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies	492:600	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	3	14	theme	sialic	507:512	arg1	residues					519:526	sialic acid residues	507:526	sialic acid residues from N-glycans of insulin receptor (IR)	507:566	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	0	15	theme	N-glycans	78:86	arg1	example					67:73	example	67:73	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.	0:107	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	5	16	from	simulations	779:789	arg1	environments					815:826	different environments	805:826	different environments	805:826	In this study, we performed molecular dynamics simulations of glycans in different environments.
34343291	1	17	from	bank	282:285	arg1	structures					255:264	all the protein structures	239:264	all the protein structures in protein data bank (PDB)	239:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	17	from	bank	282:285	arg1	%					234:234	only about 10%	221:234	only about 10% of all the protein structures in protein data bank (PDB)	221:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	6	18	from	effects	844:850	arg1	glycan					885:890	the glycan	881:890	the glycan	881:890	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	6	18	from	effects	844:850	arg1	dynamics					911:918	the dynamics	907:918	the dynamics of leucine-rich repeat L1 domain of the IR ectodomain	907:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	2	19	theme	composition	317:327	arg1	Modifications					294:306	Modifications	294:306	Modifications of sugar composition in glycoproteins	294:344	Modifications of sugar composition in glycoproteins profoundly impact the overall physiology of the organism.
34343291	6	20	theme	domain	946:951	arg1	dynamics					911:918	the dynamics	907:918	the dynamics of leucine-rich repeat L1 domain of the IR ectodomain	907:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	6	21	theme	removal	855:861	arg1	effects					844:850	the effects	840:850	the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain	840:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	2	22	from	Modifications	294:306	arg1	glycoproteins					332:344	glycoproteins	332:344	glycoproteins	332:344	Modifications of sugar composition in glycoproteins profoundly impact the overall physiology of the organism.
34343291	2	23	theme	overall	368:374	arg1	physiology					376:385	the overall physiology	364:385	the overall physiology of the organism	364:401	Modifications of sugar composition in glycoproteins profoundly impact the overall physiology of the organism.
34343291	0	24	theme	insulin	91:97	arg1	receptor					99:106	insulin receptor	91:106	insulin receptor	91:106	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	0	25	from	composition	29:39	arg1	Effects					0:6	Effects	0:6	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.	0:107	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	7	26	from	perturbations	987:999	arg1	dynamics					1014:1021	L1 domain dynamics	1004:1021	L1 domain dynamics	1004:1021	We observed perturbations in L1 domain dynamics as a result of the removal of sialic acid.
34343291	7	27	theme	sialic	1053:1058	arg1	acid					1060:1063	sialic acid	1053:1063	sialic acid	1053:1063	We observed perturbations in L1 domain dynamics as a result of the removal of sialic acid.
34343291	10	28	from	changes	1429:1435	arg1	composition					1447:1457	glycan composition	1440:1457	glycan composition	1440:1457	Our observations will further aid in understanding the role of sugars in maintaining homeostasis and how changes in glycan composition may lead to perturbations in homeostasis, ultimately leading to conditions such as insulin resistance.
34343291	4	29	theme	such	607:610	arg1	modifications					612:624	such modifications	607:624	such modifications	607:624	How such modifications affect the glycan-glycoprotein dynamics, and ultimately their function is not clearly understood to date.
34343291	5	30	theme	molecular	760:768	arg1	simulations					779:789	molecular dynamics simulations	760:789	molecular dynamics simulations of glycans in different environments	760:826	In this study, we performed molecular dynamics simulations of glycans in different environments.
34343291	9	31	theme	long-range	1292:1301	arg1	dynamics					1314:1321	long-range allosteric dynamics	1292:1321	long-range allosteric dynamics	1292:1321	These changes are accompanied by perturbations in glycan-protein interactions and perturbation of long-range allosteric dynamics.
34343291	5	32	theme	dynamics	770:777	arg1	simulations					779:789	molecular dynamics simulations	760:789	molecular dynamics simulations of glycans in different environments	760:826	In this study, we performed molecular dynamics simulations of glycans in different environments.
34343291	1	33	theme	protein	247:253	arg1	structures					255:264	all the protein structures	239:264	all the protein structures in protein data bank (PDB)	239:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	34	from	structures	255:264	arg1	bank					282:285	protein data bank	269:285	protein data bank (PDB)	269:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	34	from	structures	255:264	arg1	PDB					288:290	PDB	288:290	PDB	288:290	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	8	35	theme	insulin	1169:1175	arg1	binding					1177:1183	insulin binding	1169:1183	insulin binding with IR	1169:1191	The perturbations include an increase in the flexibility of insulin-binding residues, which may affect insulin binding with IR.
34343291	9	36	from	perturbations	1227:1239	arg1	interactions					1259:1270	glycan-protein interactions	1244:1270	glycan-protein interactions	1244:1270	These changes are accompanied by perturbations in glycan-protein interactions and perturbation of long-range allosteric dynamics.
34343291	1	37	theme	structures	255:264	arg1	structures					255:264	all the protein structures	239:264	all the protein structures in protein data bank (PDB)	239:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	37	theme	structures	255:264	arg1	%					234:234	only about 10%	221:234	only about 10% of all the protein structures in protein data bank (PDB)	221:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	7	38	theme	L1	1004:1005	arg1	dynamics					1014:1021	L1 domain dynamics	1004:1021	L1 domain dynamics	1004:1021	We observed perturbations in L1 domain dynamics as a result of the removal of sialic acid.
34343291	3	39	theme	acid	514:517	arg1	residues					519:526	sialic acid residues	507:526	sialic acid residues from N-glycans of insulin receptor (IR)	507:566	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	2	40	theme	organism	394:401	arg1	physiology					376:385	the overall physiology	364:385	the overall physiology of the organism	364:401	Modifications of sugar composition in glycoproteins profoundly impact the overall physiology of the organism.
34343291	0	41	theme	changes	11:17	arg1	Effects					0:6	Effects	0:6	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.	0:107	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	2	42	gly	glycoproteins	332:344	arg1	glycoproteins					332:344	glycoproteins	332:344	glycoproteins	332:344	Modifications of sugar composition in glycoproteins profoundly impact the overall physiology of the organism.
34343291	2	43	theme	sugar	311:315	arg1	composition					317:327	sugar composition	311:327	sugar composition	311:327	Modifications of sugar composition in glycoproteins profoundly impact the overall physiology of the organism.
34343291	8	44	theme	residues	1142:1149	arg1	flexibility					1111:1121	the flexibility	1107:1121	the flexibility of insulin-binding residues	1107:1149	The perturbations include an increase in the flexibility of insulin-binding residues, which may affect insulin binding with IR.
34343291	1	45	theme	protein	269:275	arg1	bank					282:285	protein data bank	269:285	protein data bank (PDB)	269:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	45	theme	protein	269:275	arg1	PDB					288:290	PDB	288:290	PDB	288:290	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	46	from	%	234:234	arg1	bank					282:285	protein data bank	269:285	protein data bank (PDB)	269:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	46	from	%	234:234	arg1	PDB					288:290	PDB	288:290	PDB	288:290	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	0	47	from	example	67:73	arg1	receptor					99:106	insulin receptor	91:106	insulin receptor	91:106	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	3	48	theme	receptor	554:561	arg1	N-glycans					533:541	N-glycans	533:541	N-glycans of insulin receptor (IR)	533:566	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	5	49	theme	different	805:813	arg1	environments					815:826	different environments	805:826	different environments	805:826	In this study, we performed molecular dynamics simulations of glycans in different environments.
34343291	0	50	theme	glycan	22:27	arg1	composition					29:39	glycan composition	22:39	glycan composition	22:39	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	1	51	theme	data	277:280	arg1	bank					282:285	protein data bank	269:285	protein data bank (PDB)	269:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	51	theme	data	277:280	arg1	PDB					288:290	PDB	288:290	PDB	288:290	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	8	52	theme	insulin-binding	1126:1140	arg1	residues					1142:1149	insulin-binding residues	1126:1149	insulin-binding residues	1126:1149	The perturbations include an increase in the flexibility of insulin-binding residues, which may affect insulin binding with IR.
34343291	3	53	theme	experimental	581:592	arg1	studies					594:600	various experimental studies	573:600	various experimental studies	573:600	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	9	54	from	perturbation	1276:1287	arg1	interactions					1259:1270	glycan-protein interactions	1244:1270	glycan-protein interactions	1244:1270	These changes are accompanied by perturbations in glycan-protein interactions and perturbation of long-range allosteric dynamics.
34343291	6	55	theme	ectodomain	963:972	arg1	ectodomain					963:972	the IR ectodomain	956:972	the IR ectodomain	956:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	6	55	theme	ectodomain	963:972	arg1	domain					946:951	leucine-rich repeat L1 domain	923:951	leucine-rich repeat L1 domain of the IR ectodomain	923:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	0	56	theme	glycoprotein	44:55	arg1	dynamics					57:64	glycoprotein dynamics	44:64	glycoprotein dynamics	44:64	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	9	57	theme	dynamics	1314:1321	arg1	perturbation					1276:1287	perturbation	1276:1287	perturbation of long-range allosteric dynamics	1276:1321	These changes are accompanied by perturbations in glycan-protein interactions and perturbation of long-range allosteric dynamics.
34343291	9	57	theme	dynamics	1314:1321	arg1	perturbations					1227:1239	perturbations	1227:1239	perturbations in glycan-protein interactions	1227:1270	These changes are accompanied by perturbations in glycan-protein interactions and perturbation of long-range allosteric dynamics.
34343291	4	58	gly	glycan-glycoprotein	637:655	arg1	glycan-glycoprotein					637:655	glycan-glycoprotein	637:655	glycan-glycoprotein	637:655	How such modifications affect the glycan-glycoprotein dynamics, and ultimately their function is not clearly understood to date.
34343291	3	59	theme	such	408:411	arg1	example					413:419	One such example	404:419	One such example	404:419	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	3	59	theme	such	408:411	arg1	development					428:438	the development	424:438	the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies	424:600	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	9	60	theme	glycan-protein	1244:1257	arg1	interactions					1259:1270	glycan-protein interactions	1244:1270	glycan-protein interactions	1244:1270	These changes are accompanied by perturbations in glycan-protein interactions and perturbation of long-range allosteric dynamics.
34343291	6	61	theme	sialic	866:871	arg1	acid					873:876	sialic acid	866:876	sialic acid	866:876	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	10	62	from	perturbations	1471:1483	arg1	homeostasis					1488:1498	homeostasis	1488:1498	homeostasis	1488:1498	Our observations will further aid in understanding the role of sugars in maintaining homeostasis and how changes in glycan composition may lead to perturbations in homeostasis, ultimately leading to conditions such as insulin resistance.
34343291	8	63	from	increase	1095:1102	arg1	flexibility					1111:1121	the flexibility	1107:1121	the flexibility of insulin-binding residues	1107:1149	The perturbations include an increase in the flexibility of insulin-binding residues, which may affect insulin binding with IR.
34343291	3	64	theme	insulin	546:552	arg1	receptor					554:561	insulin receptor	546:561	insulin receptor (IR)	546:566	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	3	64	theme	insulin	546:552	arg1	IR					564:565	IR	564:565	IR	564:565	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	10	65	dep	understanding	1361:1373	arg1	lead					1463:1466	lead	1463:1466	lead	1463:1466	Our observations will further aid in understanding the role of sugars in maintaining homeostasis and how changes in glycan composition may lead to perturbations in homeostasis, ultimately leading to conditions such as insulin resistance.
34343291	10	66	theme	insulin	1542:1548	arg1	resistance					1550:1559	insulin resistance	1542:1559	insulin resistance	1542:1559	Our observations will further aid in understanding the role of sugars in maintaining homeostasis and how changes in glycan composition may lead to perturbations in homeostasis, ultimately leading to conditions such as insulin resistance.
34343291	0	67	gly	glycoprotein	44:55	arg1	glycoprotein					44:55	glycoprotein dynamics	44:64	glycoprotein dynamics	44:64	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	7	68	theme	acid	1060:1063	arg1	removal					1042:1048	the removal	1038:1048	the removal of sialic acid	1038:1063	We observed perturbations in L1 domain dynamics as a result of the removal of sialic acid.
34343291	3	69	theme	insulin	443:449	arg1	resistance					451:460	insulin resistance	443:460	insulin resistance	443:460	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	6	70	theme	IR	960:961	arg1	ectodomain					963:972	the IR ectodomain	956:972	the IR ectodomain	956:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	1	71	located	observed	209:216	arg2	it					203:204	it	203:204	it	203:204	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	71	located	observed	209:216	arg1	structures					255:264	all the protein structures	239:264	all the protein structures in protein data bank (PDB)	239:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	1	71	located	observed	209:216	arg1	%					234:234	only about 10%	221:234	only about 10% of all the protein structures in protein data bank (PDB)	221:291	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	3	72	theme	various	573:579	arg1	studies					594:600	various experimental studies	573:600	various experimental studies	573:600	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	3	73	theme	resistance	451:460	arg1	example					413:419	One such example	404:419	One such example	404:419	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	3	73	theme	resistance	451:460	arg1	development					428:438	the development	424:438	the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies	424:600	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	5	74	theme	glycans	794:800	arg1	simulations					779:789	molecular dynamics simulations	760:789	molecular dynamics simulations of glycans in different environments	760:826	In this study, we performed molecular dynamics simulations of glycans in different environments.
34343291	3	75	from	N-glycans	533:541	arg1	residues					519:526	sialic acid residues	507:526	sialic acid residues from N-glycans of insulin receptor (IR)	507:566	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	3	75	from	N-glycans	533:541	arg1	removal					496:502	the removal	492:502	the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies	492:600	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
34343291	6	76	theme	leucine-rich	923:934	arg1	ectodomain					963:972	the IR ectodomain	956:972	the IR ectodomain	956:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	6	76	theme	leucine-rich	923:934	arg1	domain					946:951	leucine-rich repeat L1 domain	923:951	leucine-rich repeat L1 domain of the IR ectodomain	923:972	We studied the effects of removal of sialic acid on the glycan, as well as on the dynamics of leucine-rich repeat L1 domain of the IR ectodomain.
34343291	8	77	with	binding	1177:1183	arg1	IR					1190:1191	IR	1190:1191	IR	1190:1191	The perturbations include an increase in the flexibility of insulin-binding residues, which may affect insulin binding with IR.
34343291	0	78	dep	Effects	0:6	arg1	example					67:73	example	67:73	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.	0:107	Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.
34343291	1	79	from	modifications	167:179	arg1	proteins					184:191	proteins	184:191	proteins	184:191	Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB).
34343291	4	80	theme	glycan-glycoprotein	637:655	arg1	dynamics					657:664	the glycan-glycoprotein dynamics	633:664	the glycan-glycoprotein dynamics	633:664	How such modifications affect the glycan-glycoprotein dynamics, and ultimately their function is not clearly understood to date.
34343291	3	81	from	studies	594:600	arg1	removal					496:502	the removal	492:502	the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies	492:600	One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.
32776107	11	0	theme	N.	1408:1409	arg1	lactamica					1411:1419	N. lactamica	1408:1419	N. lactamica	1408:1419	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	6	1	theme	lactamica	855:863	arg1	strains					805:811	strains	805:811	strains of N. gonorrhoeae, N. meningitidis and N. lactamica	805:863	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	2	2	theme	glycosylation	362:374	arg1	systems					376:382	related protein glycosylation systems	346:382	related protein glycosylation systems	346:382	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	5	3	theme	di-N-acetyl	708:718	arg1	acid					731:734	di-N-acetyl glucuronic acid	708:734	di-N-acetyl glucuronic acid at the third position of a tetrasaccharide	708:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	2	4	theme	glycosylation	291:303	arg1	distribution					316:327	protein glycosylation (pgl) gene distribution	283:327	protein glycosylation (pgl) gene distribution	283:327	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	5	5	from	position	749:756	arg1	addition					696:703	the addition	692:703	the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide	692:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	5	5	from	position	749:756	arg1	acid					731:734	di-N-acetyl glucuronic acid	708:734	di-N-acetyl glucuronic acid at the third position of a tetrasaccharide	708:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	8	6	theme	UDP-glucuronic	1025:1038	arg1	GlcNAcA					1046:1052	GlcNAcA	1046:1052	GlcNAcA	1046:1052	glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis.
32776107	8	6	theme	UDP-glucuronic	1025:1038	arg1	acid					1040:1043	UDP-glucuronic acid	1025:1043	UDP-glucuronic acid (GlcNAcA)	1025:1053	glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis.
32776107	6	7	theme	N.	832:833	arg1	meningitidis					835:846	N. meningitidis	832:846	N. meningitidis	832:846	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	11	8	theme	pglG	1370:1373	arg1	alleles					1375:1381	select pglG alleles	1363:1381	select pglG alleles from N. meningitidis and N. lactamica	1363:1419	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	6	9	theme	gonorrhoeae	819:829	arg1	strains					805:811	strains	805:811	strains of N. gonorrhoeae, N. meningitidis and N. lactamica	805:863	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	2	10	theme	gene	311:314	arg1	distribution					316:327	protein glycosylation (pgl) gene distribution	283:327	protein glycosylation (pgl) gene distribution	283:327	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	13	11	theme	glycosyltransferase	1819:1837	arg1	function					1839:1846	bacterial glycosyltransferase function	1809:1846	bacterial glycosyltransferase function	1809:1846	Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.
32776107	0	12	theme	Neisseria	124:132	arg1	system					114:119	the O-linked protein glycosylation system	79:119	the O-linked protein glycosylation system of Neisseria	79:132	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	2	13	theme	pgl	306:308	arg1	distribution					316:327	protein glycosylation (pgl) gene distribution	283:327	protein glycosylation (pgl) gene distribution	283:327	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	1	14	gly	Glycosylation	135:147	arg1	species					216:222	bacterial species	206:222	bacterial species of Neisseria of import to human disease	206:262	Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease.
32776107	1	14	gly	Glycosylation	135:147	arg1	proteins					161:168	multiple proteins	152:168	multiple proteins	152:168	Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease.
32776107	9	15	theme	Neisseria	1259:1267	arg1	genus					1269:1273	the Neisseria genus	1255:1273	the Neisseria genus	1255:1273	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	1	16	theme	Neisseria	227:235	arg1	species					216:222	bacterial species	206:222	bacterial species of Neisseria of import to human disease	206:262	Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease.
32776107	12	17	theme	N.	1616:1617	arg1	gonorrhoeae					1619:1629	N. gonorrhoeae	1616:1629	N. gonorrhoeae	1616:1629	Similar experiments using pglG from N. gonorrhoeae failed to find any evidence of function suggesting that those alleles are missense pseudogenes.
32776107	5	18	theme	acid	731:734	arg1	addition					696:703	the addition	692:703	the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide	692:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	11	19	from	lactamica	1411:1419	arg1	alleles					1375:1381	select pglG alleles	1363:1381	select pglG alleles from N. meningitidis and N. lactamica	1363:1419	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	2	20	theme	Recent	265:270	arg1	studies					272:278	Recent studies	265:278	Recent studies of protein glycosylation (pgl) gene distribution	265:327	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	9	21	from	functionality	1203:1215	arg1	species					1238:1244	species	1238:1244	species spanning the Neisseria genus	1238:1273	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	9	22	theme	N.	1305:1306	arg1	subsp					1317:1321	N. elongata subsp	1305:1321	N. elongata subsp	1305:1321	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	1	23	theme	proteins	161:168	arg1	Glycosylation					135:147	Glycosylation	135:147	Glycosylation of multiple proteins via O-linkage	135:182	Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease.
32776107	4	24	theme	these	542:546	arg1	these					542:546	these	542:546	these	542:546	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	4	24	theme	these	542:546	arg1	One					535:537	One	535:537	One	535:537	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	11	25	theme	glycan	1544:1549	arg1	repertoire					1551:1560	an expanded glycan repertoire	1532:1560	an expanded glycan repertoire	1532:1560	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	0	26	theme	protein	92:98	arg1	glycosylation					100:112	O-linked protein glycosylation	83:112	the O-linked protein glycosylation system of Neisseria	79:132	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	8	27	theme	N.	1064:1065	arg1	gonorrhoeae					1067:1077	N. gonorrhoeae	1064:1077	N. gonorrhoeae	1064:1077	glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis.
32776107	7	28	theme	elongata	978:985	arg1	subsp					987:991	N. elongata subsp	975:991	N. elongata subsp	975:991	Moreover, PglG function in N. elongata subsp.
32776107	13	29	theme	distinct	1908:1915	arg1	lineages					1930:1937	distinct phylogenetic lineages	1908:1937	distinct phylogenetic lineages	1908:1937	Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.
32776107	2	30	theme	nonpathogenic	421:433	arg1	species					435:441	nonpathogenic species	421:441	nonpathogenic species	421:441	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	11	31	theme	N-acetyl-hexosamine	1461:1479	arg1	incorporation					1441:1453	incorporation	1441:1453	incorporation of an N-acetyl-hexosamine at the third position	1441:1501	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	0	32	theme	Allelic	0:6	arg1	polymorphisms					8:20	Allelic polymorphisms	0:20	Allelic polymorphisms in a glycosyltransferase gene	0:50	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	11	33	from	potential	1518:1526	arg1	species					1571:1577	those species	1565:1577	those species	1565:1577	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	8	34	theme	N.	1100:1101	arg1	lactamica					1103:1111	N. lactamica	1100:1111	N. lactamica	1100:1111	glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis.
32776107	13	35	theme	phylogenetic	1917:1928	arg1	lineages					1930:1937	distinct phylogenetic lineages	1908:1937	distinct phylogenetic lineages	1908:1937	Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.
32776107	3	36	theme	pgl	487:489	arg1	status					496:501	pgl gene status	487:501	pgl gene status	487:501	However, there are inconsistencies between pgl gene status and observed glycan structures.
32776107	0	37	theme	glycosyltransferase	27:45	arg1	gene					47:50	a glycosyltransferase gene	25:50	a glycosyltransferase gene	25:50	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	11	38	from	position	1494:1501	arg1	incorporation					1441:1453	incorporation	1441:1453	incorporation of an N-acetyl-hexosamine at the third position	1441:1501	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	0	39	link	O-linked	83:90	arg1	glycosylation					100:112	O-linked protein glycosylation	83:112	the O-linked protein glycosylation system of Neisseria	79:132	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	2	40	theme	protein	354:360	arg1	systems					376:382	related protein glycosylation systems	346:382	related protein glycosylation systems	346:382	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	4	41	theme	widespread	563:572	arg1	distribution					574:585	the widespread distribution	559:585	the widespread distribution of pglG	559:593	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	9	42	theme	pglG	1220:1223	arg1	alleles					1225:1231	pglG alleles	1220:1231	pglG alleles from species spanning the Neisseria genus	1220:1273	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	3	43	theme	observed	507:514	arg1	structures					523:532	observed glycan structures	507:532	observed glycan structures	507:532	However, there are inconsistencies between pgl gene status and observed glycan structures.
32776107	4	44	theme	Neisseria	635:643	arg1	subsp					654:658	Neisseria elongata subsp	635:658	Neisseria elongata subsp	635:658	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	13	45	theme	such	1869:1872	arg1	alterations					1874:1884	such alterations	1869:1884	such alterations	1869:1884	Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.
32776107	6	46	from	presence	917:924	arg1	backgrounds					935:945	these backgrounds	929:945	these backgrounds	929:945	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	6	47	theme	N.	852:853	arg1	lactamica					855:863	N. lactamica	852:863	N. lactamica	852:863	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	8	48	theme	UDP-GlcNAcA	1164:1174	arg1	synthesis					1176:1184	UDP-GlcNAcA synthesis	1164:1184	UDP-GlcNAcA synthesis	1164:1184	glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis.
32776107	6	49	theme	meningitidis	835:846	arg1	strains					805:811	strains	805:811	strains of N. gonorrhoeae, N. meningitidis and N. lactamica	805:863	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	2	50	theme	protein	283:289	arg1	distribution					316:327	protein glycosylation (pgl) gene distribution	283:327	protein glycosylation (pgl) gene distribution	283:327	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	11	51	theme	select	1363:1368	arg1	alleles					1375:1381	select pglG alleles	1363:1381	select pglG alleles from N. meningitidis and N. lactamica	1363:1419	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	9	52	theme	alleles	1225:1231	arg1	functionality					1203:1215	the functionality	1199:1215	the functionality of pglG alleles from species spanning the Neisseria genus	1199:1273	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	2	53	theme	distribution	316:327	arg1	studies					272:278	Recent studies	265:278	Recent studies of protein glycosylation (pgl) gene distribution	265:327	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	13	54	theme	bacterial	1809:1817	arg1	function					1839:1846	bacterial glycosyltransferase function	1809:1846	bacterial glycosyltransferase function	1809:1846	Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.
32776107	5	55	theme	third	743:747	arg1	position					749:756	the third position	739:756	the third position of a tetrasaccharide	739:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	6	56	theme	N.	816:817	arg1	gonorrhoeae					819:829	N. gonorrhoeae	816:829	N. gonorrhoeae	816:829	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	1	57	theme	bacterial	206:214	arg1	species					216:222	bacterial species	206:222	bacterial species of Neisseria of import to human disease	206:262	Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease.
32776107	11	58	theme	N.	1388:1389	arg1	meningitidis					1391:1402	N. meningitidis	1388:1402	N. meningitidis	1388:1402	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	2	59	theme	related	346:352	arg1	systems					376:382	related protein glycosylation systems	346:382	related protein glycosylation systems	346:382	Recent studies of protein glycosylation (pgl) gene distribution established that related protein glycosylation systems occur throughout the genus including nonpathogenic species.
32776107	13	60	theme	allelic	1777:1783	arg1	polymorphisms					1785:1797	allelic polymorphisms	1777:1797	allelic polymorphisms	1777:1797	Taken together, the results are emblematic of how allelic polymorphisms can shape bacterial glycosyltransferase function and demonstrate that such alterations may be constrained to distinct phylogenetic lineages.
32776107	5	61	theme	tetrasaccharide	763:777	arg1	position					749:756	the third position	739:756	the third position of a tetrasaccharide	739:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	5	62	theme	glucuronic	720:729	arg1	acid					731:734	di-N-acetyl glucuronic acid	708:734	di-N-acetyl glucuronic acid at the third position of a tetrasaccharide	708:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	9	63	from	species	1238:1244	arg1	functionality					1203:1215	the functionality	1199:1215	the functionality of pglG alleles from species spanning the Neisseria genus	1199:1273	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	9	63	from	species	1238:1244	arg1	alleles					1225:1231	pglG alleles	1220:1231	pglG alleles from species spanning the Neisseria genus	1220:1273	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	9	64	theme	genetic	1278:1284	arg1	complementation					1286:1300	genetic complementation	1278:1300	genetic complementation in N. elongata subsp	1278:1321	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	1	65	theme	multiple	152:159	arg1	proteins					161:168	multiple proteins	152:168	multiple proteins	152:168	Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease.
32776107	0	66	theme	O-linked	83:90	arg1	glycosylation					100:112	O-linked protein glycosylation	83:112	the O-linked protein glycosylation system of Neisseria	79:132	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	9	67	theme	elongata	1308:1315	arg1	subsp					1317:1321	N. elongata subsp	1305:1321	N. elongata subsp	1305:1321	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	0	68	from	polymorphisms	8:20	arg1	gene					47:50	a glycosyltransferase gene	25:50	a glycosyltransferase gene	25:50	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	11	69	theme	expanded	1535:1542	arg1	repertoire					1551:1560	an expanded glycan repertoire	1532:1560	an expanded glycan repertoire	1532:1560	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	0	70	theme	glycosylation	100:112	arg1	system					114:119	the O-linked protein glycosylation system	79:119	the O-linked protein glycosylation system of Neisseria	79:132	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	11	71	from	meningitidis	1391:1402	arg1	alleles					1375:1381	select pglG alleles	1363:1381	select pglG alleles from N. meningitidis and N. lactamica	1363:1419	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	12	72	theme	Similar	1580:1586	arg1	experiments					1588:1598	Similar experiments	1580:1598	Similar experiments using pglG from N. gonorrhoeae	1580:1629	Similar experiments using pglG from N. gonorrhoeae failed to find any evidence of function suggesting that those alleles are missense pseudogenes.
32776107	4	73	from	glycosyltransferase	607:625	arg1	subsp					654:658	Neisseria elongata subsp	635:658	Neisseria elongata subsp	635:658	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	8	74	theme	N.	1080:1081	arg1	meningitidis					1083:1094	N. meningitidis	1080:1094	N. meningitidis	1080:1094	glycolytica minimally requires UDP-glucuronic acid (GlcNAcA), and yet N. gonorrhoeae, N. meningitidis and N. lactamica lack pglJ, the gene whose product is essential for UDP-GlcNAcA synthesis.
32776107	7	75	theme	N.	975:976	arg1	subsp					987:991	N. elongata subsp	975:991	N. elongata subsp	975:991	Moreover, PglG function in N. elongata subsp.
32776107	12	76	theme	missense	1705:1712	arg1	alleles					1693:1699	those alleles	1687:1699	those alleles	1687:1699	Similar experiments using pglG from N. gonorrhoeae failed to find any evidence of function suggesting that those alleles are missense pseudogenes.
32776107	12	76	theme	missense	1705:1712	arg1	pseudogenes					1714:1724	missense pseudogenes	1705:1724	missense pseudogenes	1705:1724	Similar experiments using pglG from N. gonorrhoeae failed to find any evidence of function suggesting that those alleles are missense pseudogenes.
32776107	4	77	theme	pglG	590:593	arg1	distribution					574:585	the widespread distribution	559:585	the widespread distribution of pglG	559:593	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	12	78	theme	function	1662:1669	arg1	evidence					1650:1657	any evidence	1646:1657	any evidence of function suggesting that those alleles are missense pseudogenes	1646:1724	Similar experiments using pglG from N. gonorrhoeae failed to find any evidence of function suggesting that those alleles are missense pseudogenes.
32776107	11	79	theme	third	1488:1492	arg1	position					1494:1501	the third position	1484:1501	the third position	1484:1501	The results indicate that select pglG alleles from N. meningitidis and N. lactamica are associated with incorporation of an N-acetyl-hexosamine at the third position and reveal the potential for an expanded glycan repertoire in those species.
32776107	3	80	theme	gene	491:494	arg1	status					496:501	pgl gene status	487:501	pgl gene status	487:501	However, there are inconsistencies between pgl gene status and observed glycan structures.
32776107	0	81	theme	glycan	58:63	arg1	repertoire					65:74	glycan repertoire	58:74	glycan repertoire	58:74	Allelic polymorphisms in a glycosyltransferase gene shape glycan repertoire in the O-linked protein glycosylation system of Neisseria.
32776107	4	82	dep	glycosyltransferase	607:625	arg1	that					627:630	that	627:630	that	627:630	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	5	83	from	addition	696:703	arg1	position					749:756	the third position	739:756	the third position of a tetrasaccharide	739:777	glycolytica is responsible for the addition of di-N-acetyl glucuronic acid at the third position of a tetrasaccharide.
32776107	6	84	theme	glycan	869:874	arg1	structures					876:885	no glycan structures	866:885	no glycan structures	866:885	Despite pglG residing in strains of N. gonorrhoeae, N. meningitidis and N. lactamica, no glycan structures have been correlated with its presence in these backgrounds.
32776107	4	85	theme	elongata	645:652	arg1	subsp					654:658	Neisseria elongata subsp	635:658	Neisseria elongata subsp	635:658	One of these relates to the widespread distribution of pglG, encoding a glycosyltransferase that in Neisseria elongata subsp.
32776107	3	86	theme	glycan	516:521	arg1	structures					523:532	observed glycan structures	507:532	observed glycan structures	507:532	However, there are inconsistencies between pgl gene status and observed glycan structures.
32776107	9	87	from	complementation	1286:1300	arg1	subsp					1317:1321	N. elongata subsp	1305:1321	N. elongata subsp	1305:1321	We examined the functionality of pglG alleles from species spanning the Neisseria genus by genetic complementation in N. elongata subsp.
32776107	1	88	theme	human	250:254	arg1	disease					256:262	human disease	250:262	human disease	250:262	Glycosylation of multiple proteins via O-linkage is well documented in bacterial species of Neisseria of import to human disease.
32409993	7	0	theme	misfolded	1148:1156	arg1	bri1-GFPs					1158:1166	the misfolded bri1-GFPs	1144:1166	the misfolded bri1-GFPs exiting from the ER	1144:1186	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	9	1	theme	monitoring	1536:1545	arg1	role					1547:1550	a protective or monitoring role	1520:1550	a protective or monitoring role	1520:1550	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	1	2	theme	folding	149:155	arg1	state					157:161	the folding state	145:161	the folding state of associated protein or the distance from structural defects	145:223	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	3	3	from	N-glycans	528:536	arg1	protein					543:549	a protein	541:549	a protein	541:549	The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein.
32409993	8	4	theme	N-glycans	1429:1437	arg1	presence					1408:1415	the presence	1404:1415	the presence of multiple N-glycans distal to the local defects	1404:1465	We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects.
32409993	6	5	theme	obvious	790:796	arg1	effect					798:803	no obvious effect	787:803	no obvious effect	787:803	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	9	6	from	state	1577:1581	arg1	defects					1637:1643	structural defects	1626:1643	structural defects	1626:1643	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	8	7	theme	multiple	1420:1427	arg1	N-glycans					1429:1437	multiple N-glycans	1420:1437	multiple N-glycans distal to the local defects	1420:1465	We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects.
32409993	7	8	theme	local	1042:1046	arg1	defects					1059:1065	local structural defects	1042:1065	local structural defects	1042:1065	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	1	9	from	state	157:161	arg1	defects					217:223	structural defects	206:223	structural defects	206:223	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	1	10	theme	protective	102:111	arg1	role					127:130	a protective or monitoring role	100:130	a protective or monitoring role	100:130	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	7	11	theme	structural	1048:1057	arg1	defects					1059:1065	local structural defects	1042:1065	local structural defects	1042:1065	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	9	12	theme	or	1533:1534	arg1	role					1547:1550	a protective or monitoring role	1520:1550	a protective or monitoring role	1520:1550	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	9	13	from	defects	1637:1643	arg1	state					1577:1581	the folding state	1565:1581	the folding state of associated protein or the distance from structural defects	1565:1643	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	9	13	from	defects	1637:1643	arg1	protein					1597:1603	associated protein	1586:1603	associated protein	1586:1603	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	9	13	from	defects	1637:1643	arg1	distance					1612:1619	the distance	1608:1619	the distance from structural defects	1608:1643	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	7	14	theme	N-glycan	1124:1131	arg1	addition					1112:1119	the artificial addition	1097:1119	the artificial addition of N-glycan	1097:1131	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	2	15	theme	associated	338:347	arg1	N-glycans					349:357	the associated N-glycans	334:357	the associated N-glycans	334:357	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	3	16	from	redundancy	514:523	arg1	protein					543:549	a protein	541:549	a protein	541:549	The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein.
32409993	2	17	theme	protein	381:387	arg1	folding					389:395	protein folding	381:395	protein folding	381:395	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	7	18	theme	ER	1080:1081	arg1	retention					1083:1091	the ER retention	1076:1091	the ER retention	1076:1091	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	8	19	theme	local	1453:1457	arg1	defects					1459:1465	the local defects	1449:1465	the local defects	1449:1465	We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects.
32409993	9	20	theme	associated	1586:1595	arg1	protein					1597:1603	associated protein	1586:1603	associated protein	1586:1603	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	6	21	theme	single	767:772	arg1	N-glycan					774:781	single N-glycan	767:781	single N-glycan	767:781	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	3	22	theme	N-glycans	528:536	arg1	redundancy					514:523	the redundancy	510:523	the redundancy of N-glycans on a protein	510:549	The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein.
32409993	1	23	theme	associated	166:175	arg1	protein					177:183	associated protein	166:183	associated protein	166:183	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	9	24	theme	protein	1597:1603	arg1	state					1577:1581	the folding state	1565:1581	the folding state of associated protein or the distance from structural defects	1565:1643	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	4	25	theme	protein	618:624	arg1	secretion					626:634	protein secretion	618:634	protein secretion	618:634	In this study, we used BRI1 to decipher the roles of N-glycans on protein secretion and function.
32409993	2	26	theme	protein	308:314	arg1	modifications					316:328	the most prevalent and complex protein modifications	277:328	the most prevalent and complex protein modifications	277:328	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	7	27	theme	misfolded	993:1001	arg1	bri1					1003:1006	misfolded bri1	993:1006	misfolded bri1	993:1006	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	1	28	theme	protein	177:183	arg1	state					157:161	the folding state	145:161	the folding state of associated protein or the distance from structural defects	145:223	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	0	29	theme	Multiple	0:7	arg1	N-glycans					9:17	Multiple N-glycans	0:17	Multiple N-glycans	0:17	Multiple N-glycans cooperate in balancing misfolded BRI1 secretion and ER retention.
32409993	9	30	theme	structural	1626:1635	arg1	defects					1637:1643	structural defects	1626:1643	structural defects	1626:1643	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	5	31	used	occupied	716:723	arg2	sites					697:701	all 14 potential N-glycosylation sites	664:701	all 14 potential N-glycosylation sites on BRI1	664:709	We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides.
32409993	5	31	used	occupied	716:723	arg2	BRI1					706:709	BRI1	706:709	BRI1	706:709	We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides.
32409993	2	32	theme	complex	300:306	arg1	modifications					316:328	the most prevalent and complex protein modifications	277:328	the most prevalent and complex protein modifications	277:328	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	6	33	theme	N-glycan	774:781	arg1	elimination					752:762	The elimination	748:762	The elimination of single N-glycan	748:781	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	3	34	theme	multiple	464:471	arg1	N-glycans					473:481	multiple N-glycans	464:481	multiple N-glycans	464:481	The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein.
32409993	7	35	theme	artificial	1101:1110	arg1	addition					1112:1119	the artificial addition	1097:1119	the artificial addition of N-glycan	1097:1131	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	8	36	theme	distal	1439:1444	arg1	N-glycans					1429:1437	multiple N-glycans	1420:1437	multiple N-glycans distal to the local defects	1420:1465	We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects.
32409993	9	37	theme	distance	1612:1619	arg1	state					1577:1581	the folding state	1565:1581	the folding state of associated protein or the distance from structural defects	1565:1643	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	2	38	theme	prevalent	286:294	arg1	modifications					316:328	the most prevalent and complex protein modifications	277:328	the most prevalent and complex protein modifications	277:328	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	1	39	theme	distance	192:199	arg1	state					157:161	the folding state	145:161	the folding state of associated protein or the distance from structural defects	145:223	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	0	40	theme	misfolded	42:50	arg1	secretion					57:65	misfolded BRI1 secretion	42:65	misfolded BRI1 secretion	42:65	Multiple N-glycans cooperate in balancing misfolded BRI1 secretion and ER retention.
32409993	8	41	from	retention	1328:1336	arg1	ER					1391:1392	the ER	1387:1392	the ER	1387:1392	We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects.
32409993	5	42	theme	potential	671:679	arg1	sites					697:701	all 14 potential N-glycosylation sites	664:701	all 14 potential N-glycosylation sites on BRI1	664:709	We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides.
32409993	6	43	from	retention	877:885	arg1	ER					925:926	ER	925:926	ER	925:926	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	6	43	from	retention	877:885	arg1	reticulum					914:922	the endoplasmic reticulum	898:922	the endoplasmic reticulum (ER)	898:927	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	4	44	from	roles	596:600	arg1	secretion					626:634	protein secretion	618:634	protein secretion	618:634	In this study, we used BRI1 to decipher the roles of N-glycans on protein secretion and function.
32409993	4	44	from	roles	596:600	arg1	function					640:647	function	640:647	function	640:647	In this study, we used BRI1 to decipher the roles of N-glycans on protein secretion and function.
32409993	5	45	theme	N-glycosylation	681:695	arg1	sites					697:701	all 14 potential N-glycosylation sites	664:701	all 14 potential N-glycosylation sites on BRI1	664:709	We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides.
32409993	5	46	from	sites	697:701	arg1	BRI1					706:709	BRI1	706:709	BRI1	706:709	We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides.
32409993	2	47	theme	Asparagine-linked	226:242	arg1	glycosylation					253:265	Asparagine-linked (Asn/N-) glycosylation	226:265	Asparagine-linked (Asn/N-) glycosylation	226:265	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	1	48	theme	structural	206:215	arg1	defects					217:223	structural defects	206:223	structural defects	206:223	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	6	49	theme	endoplasmic	902:912	arg1	ER					925:926	ER	925:926	ER	925:926	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	6	49	theme	endoplasmic	902:912	arg1	reticulum					914:922	the endoplasmic reticulum	898:922	the endoplasmic reticulum (ER)	898:927	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	6	50	theme	N-glycans	979:987	arg1	loss					945:948	the loss	941:948	the loss of multiple highly conserved N-glycans	941:987	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	1	51	theme	or	113:114	arg1	role					127:130	a protective or monitoring role	100:130	a protective or monitoring role	100:130	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	0	52	theme	BRI1	52:55	arg1	secretion					57:65	misfolded BRI1 secretion	42:65	misfolded BRI1 secretion	42:65	Multiple N-glycans cooperate in balancing misfolded BRI1 secretion and ER retention.
32409993	4	53	used	used	570:573	arg2	we					567:568	we	567:568	we	567:568	In this study, we used BRI1 to decipher the roles of N-glycans on protein secretion and function.
32409993	3	54	gly	glycoproteins	445:457	arg1	glycoproteins					445:457	many glycoproteins	440:457	many glycoproteins	440:457	The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein.
32409993	7	55	theme	structure	1266:1274	arg1	defects					1276:1282	the structure defects	1262:1282	the structure defects	1262:1282	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	1	56	theme	monitoring	116:125	arg1	role					127:130	a protective or monitoring role	100:130	a protective or monitoring role	100:130	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	3	57	from	protein	543:549	arg1	redundancy					514:523	the redundancy	510:523	the redundancy of N-glycans on a protein	510:549	The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein.
32409993	8	58	theme	bri1-9	1351:1356	arg1	retention					1328:1336	the retention	1324:1336	the retention of misfolded bri1-9 by lectins and chaperones in the ER	1324:1392	We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects.
32409993	1	59	from	defects	217:223	arg1	protein					177:183	associated protein	166:183	associated protein	166:183	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	1	59	from	defects	217:223	arg1	distance					192:199	the distance	188:199	the distance from structural defects	188:223	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	1	59	from	defects	217:223	arg1	state					157:161	the folding state	145:161	the folding state of associated protein or the distance from structural defects	145:223	N-glycans play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	6	60	theme	BRI1	808:811	arg1	secretion					813:821	BRI1 secretion	808:821	BRI1 secretion	808:821	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	7	61	theme	ER	1289:1290	arg1	recognition					1292:1302	ER recognition	1289:1302	ER recognition	1289:1302	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	5	62	gly	N-glycosylation	681:695	arg2	sites					697:701	all 14 potential N-glycosylation sites	664:701	all 14 potential N-glycosylation sites on BRI1	664:709	We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides.
32409993	5	62	gly	N-glycosylation	681:695	arg2	14					668:669	14	668:669	14	668:669	We found that all 14 potential N-glycosylation sites on BRI1 were occupied with oligosaccharides.
32409993	6	63	theme	conserved	969:977	arg1	N-glycans					979:987	multiple highly conserved N-glycans	953:987	multiple highly conserved N-glycans	953:987	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	8	64	theme	misfolded	1341:1349	arg1	bri1-9					1351:1356	misfolded bri1-9	1341:1356	misfolded bri1-9 by lectins and chaperones	1341:1382	We also found that the retention of misfolded bri1-9 by lectins and chaperones in the ER relied on the presence of multiple N-glycans distal to the local defects.
32409993	2	65	theme	modifications	316:328	arg1	one					270:272	one	270:272	one	270:272	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	2	65	theme	modifications	316:328	arg1	modifications					316:328	the most prevalent and complex protein modifications	277:328	the most prevalent and complex protein modifications	277:328	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	9	66	theme	folding	1569:1575	arg1	state					1577:1581	the folding state	1565:1581	the folding state of associated protein or the distance from structural defects	1565:1643	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	7	67	theme	N-glycans	1024:1032	arg1	absence					1013:1019	the absence	1009:1019	the absence of N-glycans next to local structural defects	1009:1065	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	0	68	theme	ER	71:72	arg1	retention					74:82	ER retention	71:82	ER retention	71:82	Multiple N-glycans cooperate in balancing misfolded BRI1 secretion and ER retention.
32409993	4	69	theme	N-glycans	605:613	arg1	roles					596:600	the roles	592:600	the roles of N-glycans on protein secretion and function	592:647	In this study, we used BRI1 to decipher the roles of N-glycans on protein secretion and function.
32409993	7	70	theme	steric	1234:1239	arg1	hindrance					1241:1249	steric hindrance	1234:1249	steric hindrance	1234:1249	To misfolded bri1, the absence of N-glycans next to local structural defects enhanced the ER retention and the artificial addition of N-glycan could help the misfolded bri1-GFPs exiting from the ER, indicating that the N-glycans might serve as steric hindrance to protect the structure defects from ER recognition.
32409993	3	71	theme	many	440:443	arg1	glycoproteins					445:457	many glycoproteins	440:457	many glycoproteins	440:457	The studies have shown that many glycoproteins hold multiple N-glycans, yet little is known about the redundancy of N-glycans on a protein.
32409993	6	72	theme	multiple	953:960	arg1	N-glycans					979:987	multiple highly conserved N-glycans	953:987	multiple highly conserved N-glycans	953:987	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	6	73	contain	had	783:785	arg2	effect					798:803	no obvious effect	787:803	no obvious effect	787:803	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	6	73	contain	had	783:785	arg1	elimination					752:762	The elimination	748:762	The elimination of single N-glycan	748:781	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	6	74	theme	BRI1	890:893	arg1	retention					877:885	the retention	873:885	the retention of BRI1 in the endoplasmic reticulum (ER)	873:927	The elimination of single N-glycan had no obvious effect on BRI1 secretion or function except N154-glycan, which resulted in the retention of BRI1 in the endoplasmic reticulum (ER), similar to the loss of multiple highly conserved N-glycans.
32409993	2	75	theme	Asn/N-	245:250	arg1	glycosylation					253:265	Asparagine-linked (Asn/N-) glycosylation	226:265	Asparagine-linked (Asn/N-) glycosylation	226:265	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	2	76	theme	crucial	364:370	arg1	roles					372:376	crucial roles	364:376	crucial roles	364:376	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32409993	9	77	theme	protective	1522:1531	arg1	role					1547:1550	a protective or monitoring role	1520:1550	a protective or monitoring role	1520:1550	Our findings revealed that the N-glycans might play a protective or monitoring role according to the folding state of associated protein or the distance from structural defects.
32409993	2	78	link	Asparagine-linked	226:242	arg1	glycosylation					253:265	Asparagine-linked (Asn/N-) glycosylation	226:265	Asparagine-linked (Asn/N-) glycosylation	226:265	Asparagine-linked (Asn/N-) glycosylation is one of the most prevalent and complex protein modifications and the associated N-glycans play crucial roles on protein folding and secretion.
32719555	4	0	theme	cancer-associated	951:967	arg1	glycoforms					969:978	cancer-associated glycoforms	951:978	cancer-associated glycoforms of MUC1	951:986	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	2	1	theme	protein	353:359	arg1	glycosylation					361:373	eukaryotic O-linked protein glycosylation	333:373	eukaryotic O-linked protein glycosylation in Escherichia coli	333:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	2	theme	serine	486:491	arg1	residues					493:500	serine residues	486:500	serine residues in acceptor motifs derived from different human O-glycoproteins	486:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	5	3	theme	applications	1189:1200	arg1	range					1143:1147	a range	1141:1147	a range of important scientific and therapeutic applications	1141:1200	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	0	4	link	O-linked	29:36	arg1	biosynthesis					51:62	orthogonal human O-linked glycoprotein biosynthesis	12:62	orthogonal human O-linked glycoprotein biosynthesis in bacteria	12:74	Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria.
32719555	2	5	gly	O-glycoproteins	550:564	arg1	O-glycoproteins					550:564	different human O-glycoproteins	534:564	different human O-glycoproteins	534:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	1	6	theme	useful	259:264	arg1	purposes					266:273	new and useful purposes	251:273	new and useful purposes	251:273	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	2	7	theme	different	534:542	arg1	O-glycoproteins					550:564	different human O-glycoproteins	534:564	different human O-glycoproteins	534:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	4	8	theme	antibody	907:914	arg1	5E5					916:918	antibody 5E5	907:918	antibody 5E5	907:918	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	3	9	theme	glycoengineered	578:592	arg1	bacteria					594:601	These same glycoengineered bacteria	567:601	These same glycoengineered bacteria	567:601	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	5	10	theme	glycoprotein	1023:1034	arg1	pathways					1049:1056	the orthogonal glycoprotein biosynthesis pathways	1008:1056	the orthogonal glycoprotein biosynthesis pathways developed here	1008:1071	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	4	11	theme	Tn-MUC1	858:864	arg1	glycoform					866:874	an antigenically authentic Tn-MUC1 glycoform	831:874	an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1	831:986	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	2	12	theme	orthogonal	309:318	arg1	pathways					320:327	orthogonal pathways	309:327	orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli	309:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	13	link	O-linked	344:351	arg1	glycosylation					361:373	eukaryotic O-linked protein glycosylation	333:373	eukaryotic O-linked protein glycosylation in Escherichia coli	333:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	1	14	theme	major	79:83	arg1	objective					85:93	A major objective	77:93	A major objective of synthetic glycobiology	77:119	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	5	15	theme	orthogonal	1012:1021	arg1	pathways					1049:1056	the orthogonal glycoprotein biosynthesis pathways	1008:1056	the orthogonal glycoprotein biosynthesis pathways developed here	1008:1071	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	1	16	theme	top	189:191	arg1	down					193:196	the top down	185:196	the top down	185:196	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	0	17	from	biosynthesis	51:62	arg1	bacteria					67:74	bacteria	67:74	bacteria	67:74	Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria.
32719555	4	18	from	able	814:817	arg1	addition					764:771	addition	764:771	addition	764:771	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	0	19	theme	orthogonal	12:21	arg1	biosynthesis					51:62	orthogonal human O-linked glycoprotein biosynthesis	12:62	orthogonal human O-linked glycoprotein biosynthesis in bacteria	12:74	Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria.
32719555	5	20	theme	diverse	1116:1122	arg1	O-glycoforms					1124:1135	structurally diverse O-glycoforms	1103:1135	structurally diverse O-glycoforms	1103:1135	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	5	21	theme	biosynthesis	1036:1047	arg1	pathways					1049:1056	the orthogonal glycoprotein biosynthesis pathways	1008:1056	the orthogonal glycoprotein biosynthesis pathways developed here	1008:1071	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	4	22	gly	glycoforms	969:978	arg1	MUC1					983:986	MUC1	983:986	MUC1	983:986	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	5	23	theme	therapeutic	1177:1187	arg1	applications					1189:1200	important scientific and therapeutic applications	1152:1200	important scientific and therapeutic applications	1152:1200	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	1	24	theme	synthetic	98:106	arg1	glycobiology					108:119	synthetic glycobiology	98:119	synthetic glycobiology	98:119	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	0	25	theme	O-linked	29:36	arg1	biosynthesis					51:62	orthogonal human O-linked glycoprotein biosynthesis	12:62	orthogonal human O-linked glycoprotein biosynthesis in bacteria	12:74	Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria.
32719555	4	26	theme	O-glycosylation-competent	774:798	arg1	bacteria					800:807	O-glycosylation-competent bacteria	774:807	O-glycosylation-competent bacteria	774:807	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	2	27	gly	glycosylation	361:373	arg1	coli					390:393	Escherichia coli	378:393	Escherichia coli	378:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	28	from	glycosylation	361:373	arg1	coli					390:393	Escherichia coli	378:393	Escherichia coli	378:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	1	29	theme	glycobiology	108:119	arg1	objective					85:93	A major objective	77:93	A major objective of synthetic glycobiology	77:119	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	1	30	theme	non-natural	211:221	arg1	ones					223:226	non-natural ones	211:226	non-natural ones from the bottom up for new and useful purposes	211:273	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	0	31	theme	human	23:27	arg1	biosynthesis					51:62	orthogonal human O-linked glycoprotein biosynthesis	12:62	orthogonal human O-linked glycoprotein biosynthesis in bacteria	12:74	Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria.
32719555	4	32	theme	antigenically	834:846	arg1	glycoform					866:874	an antigenically authentic Tn-MUC1 glycoform	831:874	an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1	831:986	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	2	33	from	residues	493:500	arg1	motifs					514:519	acceptor motifs	505:519	acceptor motifs derived from different human O-glycoproteins	505:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	34	theme	O-linked	344:351	arg1	glycosylation					361:373	eukaryotic O-linked protein glycosylation	333:373	eukaryotic O-linked protein glycosylation in Escherichia coli	333:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	35	theme	mucin-type	432:441	arg1	T					455:455	T	455:455	T	455:455	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	35	theme	mucin-type	432:441	arg1	Tn					451:452	Tn	451:452	Tn	451:452	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	35	theme	mucin-type	432:441	arg1	sialyl-T					472:479	sialyl-T	472:479	sialyl-T	472:479	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	35	theme	mucin-type	432:441	arg1	sialyl-Tn					458:466	sialyl-Tn	458:466	sialyl-Tn	458:466	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	35	theme	mucin-type	432:441	arg1	glycans					443:449	the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T	410:479	the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T	410:479	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	5	36	gly	glycoprotein	1023:1034	arg1	glycoprotein					1023:1034	the orthogonal glycoprotein biosynthesis pathways	1008:1056	the orthogonal glycoprotein biosynthesis pathways developed here	1008:1071	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	5	37	theme	important	1152:1160	arg1	applications					1189:1200	important scientific and therapeutic applications	1152:1200	important scientific and therapeutic applications	1152:1200	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	2	38	theme	cancer-associated	414:430	arg1	T					455:455	T	455:455	T	455:455	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	38	theme	cancer-associated	414:430	arg1	Tn					451:452	Tn	451:452	Tn	451:452	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	38	theme	cancer-associated	414:430	arg1	sialyl-T					472:479	sialyl-T	472:479	sialyl-T	472:479	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	38	theme	cancer-associated	414:430	arg1	sialyl-Tn					458:466	sialyl-Tn	458:466	sialyl-Tn	458:466	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	38	theme	cancer-associated	414:430	arg1	glycans					443:449	the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T	410:479	the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T	410:479	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	0	39	theme	glycoprotein	38:49	arg1	biosynthesis					51:62	orthogonal human O-linked glycoprotein biosynthesis	12:62	orthogonal human O-linked glycoprotein biosynthesis in bacteria	12:74	Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria.
32719555	2	40	theme	human	544:548	arg1	O-glycoproteins					550:564	different human O-glycoproteins	534:564	different human O-glycoproteins	534:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	3	41	theme	glycosylation	657:669	arg1	machinery					671:679	glycosylation machinery	657:679	glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction	657:758	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	3	42	theme	crude	623:627	arg1	extracts					634:641	crude cell extracts	623:641	crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction	623:758	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	4	43	gly	glycoform	866:874	arg1	Tn-MUC1					858:864	an antigenically authentic Tn-MUC1 glycoform	831:874	an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1	831:986	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	2	44	dep	glycans	443:449	arg1	T					455:455	T	455:455	T	455:455	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	44	dep	glycans	443:449	arg1	Tn					451:452	Tn	451:452	Tn	451:452	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	44	dep	glycans	443:449	arg1	sialyl-T					472:479	sialyl-T	472:479	sialyl-T	472:479	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	44	dep	glycans	443:449	arg1	sialyl-Tn					458:466	sialyl-Tn	458:466	sialyl-Tn	458:466	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	44	dep	glycans	443:449	arg1	glycans					443:449	the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T	410:479	the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T	410:479	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	45	theme	eukaryotic	333:342	arg1	glycosylation					361:373	eukaryotic O-linked protein glycosylation	333:373	eukaryotic O-linked protein glycosylation in Escherichia coli	333:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	4	46	theme	MUC1	983:986	arg1	glycoforms					969:978	cancer-associated glycoforms	951:978	cancer-associated glycoforms of MUC1	951:986	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	1	47	dep	purposes	266:273	arg1	up					244:245	up	244:245	up	244:245	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	5	48	theme	scientific	1162:1171	arg1	applications					1189:1200	important scientific and therapeutic applications	1152:1200	important scientific and therapeutic applications	1152:1200	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	3	49	used	used	608:611	arg2	bacteria					594:601	These same glycoengineered bacteria	567:601	These same glycoengineered bacteria	567:601	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	1	50	from	bottom	237:242	arg1	ones					223:226	non-natural ones	211:226	non-natural ones from the bottom up for new and useful purposes	211:273	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	3	51	theme	O-glycoproteins	722:736	arg1	construction					706:717	cell-free construction	696:717	cell-free construction of O-glycoproteins	696:736	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	0	52	gly	glycoprotein	38:49	arg1	glycoprotein					38:49	orthogonal human O-linked glycoprotein biosynthesis	12:62	orthogonal human O-linked glycoprotein biosynthesis in bacteria	12:74	Engineering orthogonal human O-linked glycoprotein biosynthesis in bacteria.
32719555	2	53	attach	derived	521:527	arg2	motifs					514:519	acceptor motifs	505:519	acceptor motifs derived from different human O-glycoproteins	505:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	53	attach	derived	521:527	arg1	O-glycoproteins					550:564	different human O-glycoproteins	534:564	different human O-glycoproteins	534:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	1	54	theme	existing	139:146	arg1	pathways					171:178	existing cellular glycosylation pathways	139:178	existing cellular glycosylation pathways	139:178	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	3	55	theme	same	573:576	arg1	bacteria					594:601	These same glycoengineered bacteria	567:601	These same glycoengineered bacteria	567:601	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	3	56	gly	O-glycoproteins	722:736	arg1	O-glycoproteins					722:736	O-glycoproteins	722:736	O-glycoproteins	722:736	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	3	57	theme	cell-free	696:704	arg1	construction					706:717	cell-free construction	696:717	cell-free construction of O-glycoproteins	696:736	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	4	58	theme	authentic	848:856	arg1	glycoform					866:874	an antigenically authentic Tn-MUC1 glycoform	831:874	an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1	831:986	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	1	59	theme	cellular	148:155	arg1	pathways					171:178	existing cellular glycosylation pathways	139:178	existing cellular glycosylation pathways	139:178	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	2	60	theme	pathways	320:327	arg1	set					302:304	a set	300:304	a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins	300:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	60	theme	pathways	320:327	arg1	pathways					320:327	orthogonal pathways	309:327	orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli	309:393	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	2	61	theme	acceptor	505:512	arg1	motifs					514:519	acceptor motifs	505:519	acceptor motifs derived from different human O-glycoproteins	505:564	Here, we have developed a set of orthogonal pathways for eukaryotic O-linked protein glycosylation in Escherichia coli that installed the cancer-associated mucin-type glycans Tn, T, sialyl-Tn and sialyl-T onto serine residues in acceptor motifs derived from different human O-glycoproteins.
32719555	5	62	theme	facile	1086:1091	arg1	access					1093:1098	facile access	1086:1098	facile access to structurally diverse O-glycoforms	1086:1135	We anticipate that the orthogonal glycoprotein biosynthesis pathways developed here will provide facile access to structurally diverse O-glycoforms for a range of important scientific and therapeutic applications.
32719555	3	63	theme	cell	629:632	arg1	extracts					634:641	crude cell extracts	623:641	crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction	623:758	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	1	64	theme	glycosylation	157:169	arg1	pathways					171:178	existing cellular glycosylation pathways	139:178	existing cellular glycosylation pathways	139:178	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32719555	4	65	from	addition	764:771	arg1	able					814:817	able	814:817	able	814:817	In addition, O-glycosylation-competent bacteria were able to generate an antigenically authentic Tn-MUC1 glycoform that exhibited reactivity with antibody 5E5, which specifically recognizes cancer-associated glycoforms of MUC1.
32719555	3	66	theme	one-pot	743:749	arg1	reaction					751:758	a one-pot reaction	741:758	a one-pot reaction	741:758	These same glycoengineered bacteria were used to supply crude cell extracts enriched with glycosylation machinery that permitted cell-free construction of O-glycoproteins in a one-pot reaction.
32719555	1	67	theme	new	251:253	arg1	purposes					266:273	new and useful purposes	251:273	new and useful purposes	251:273	A major objective of synthetic glycobiology is to re-engineer existing cellular glycosylation pathways from the top down or construct non-natural ones from the bottom up for new and useful purposes.
32842538	0	0	theme	Life	76:79	arg1	Cycle					81:85	the Zika Virus Life Cycle	61:85	the Zika Virus Life Cycle	61:85	N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle.
32842538	5	1	theme	infectious	579:588	arg1	clone					590:594	a ZIKV infectious clone	572:594	a ZIKV infectious clone	572:594	Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant.
32842538	4	2	theme	prM	491:493	arg1	glycosylation					510:522	prM and E N-linked glycosylation	491:522	prM and E N-linked glycosylation	491:522	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	0	3	theme	Virus	70:74	arg1	Cycle					81:85	the Zika Virus Life Cycle	61:85	the Zika Virus Life Cycle	61:85	N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle.
32842538	3	4	contain	contains	342:349	arg1	protein					314:320	The prM protein	306:320	The prM protein of all ZIKV strains	306:340	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	3	4	contain	contains	342:349	arg2	site					383:386	a single N-linked glycosylation site	351:386	a single N-linked glycosylation site	351:386	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	1	5	theme	important	141:149	arg1	role					151:154	an important role	138:154	an important role	138:154	Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification.
32842538	9	6	theme	ER	1269:1270	arg1	protein					1250:1256	CCAAT-enhancer-binding protein homologous protein	1208:1256	CCAAT-enhancer-binding protein homologous protein (CHOP)	1208:1263	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	6	theme	ER	1269:1270	arg1	marker					1279:1284	an ER stress marker	1266:1284	an ER stress marker	1266:1284	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	5	7	theme	N-glycan	620:627	arg1	sites					629:633	the N-glycan sites	616:633	the N-glycan sites	616:633	Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant.
32842538	0	8	from	N-glycosylation	0:14	arg1	Protein					36:42	the Pre-Membrane Protein	19:42	the Pre-Membrane Protein	19:42	N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle.
32842538	4	9	theme	E	499:499	arg1	glycosylation					510:522	prM and E N-linked glycosylation	491:522	prM and E N-linked glycosylation	491:522	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	3	10	theme	prM	310:312	arg1	protein					314:320	The prM protein	306:320	The prM protein of all ZIKV strains	306:340	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	5	11	theme	ZIKV	574:577	arg1	clone					590:594	a ZIKV infectious clone	572:594	a ZIKV infectious clone	572:594	Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant.
32842538	1	12	theme	protein	110:116	arg1	glycosylation					118:130	Asparagine (N)-linked protein glycosylation	88:130	Asparagine (N)-linked protein glycosylation	88:130	Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification.
32842538	10	13	theme	important	1387:1395	arg1	role					1397:1400	an important role	1384:1400	an important role	1384:1400	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	3	14	contain	contain	411:417	arg2	site					431:434	an N-linked site	419:434	an N-linked site in the E protein	419:451	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	3	14	contain	contain	411:417	arg1	strains					403:409	not all strains	395:409	not all strains	395:409	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	3	15	link	N-linked	360:367	arg1	site					383:386	a single N-linked glycosylation site	351:386	a single N-linked glycosylation site	351:386	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	9	16	theme	N-glycan	1159:1166	arg1	lack					1147:1150	lack	1147:1150	lack of the N-glycan on prM	1147:1173	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	3	17	theme	N-linked	360:367	arg1	site					383:386	a single N-linked glycosylation site	351:386	a single N-linked glycosylation site	351:386	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	7	18	theme	reticulum	962:970	arg1	compartment					977:987	the rough endoplasmatic reticulum (ER) compartment	938:987	the rough endoplasmatic reticulum (ER) compartment	938:987	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	6	19	theme	virions	859:865	arg1	secretion					841:849	effective secretion	831:849	effective secretion of ZIKV virions	831:865	Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions.
32842538	6	20	theme	ZIKV	761:764	arg1	constructs					771:780	ZIKV prME constructs	761:780	ZIKV prME constructs	761:780	Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions.
32842538	10	21	theme	prM	1317:1319	arg1	essential					1333:1341	essential	1333:1341	essential	1333:1341	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	10	21	theme	prM	1317:1319	arg1	N-glycan					1321:1328	the prM N-glycan	1313:1328	the prM N-glycan	1313:1328	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	10	22	theme	virion	1453:1458	arg1	assembly					1460:1467	virion assembly	1453:1467	virion assembly	1453:1467	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	8	23	theme	intermediate	1087:1098	arg1	ERGIC					1113:1117	ERGIC	1113:1117	ERGIC	1113:1117	The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization.
32842538	8	23	theme	intermediate	1087:1098	arg1	compartment					1100:1110	ER-Golgi intermediate compartment	1078:1110	the ER-Golgi intermediate compartment (ERGIC) localization	1074:1131	The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization.
32842538	4	24	from	impact	481:486	arg1	infectivity					532:542	ZIKV infectivity	527:542	ZIKV infectivity	527:542	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	4	24	from	impact	481:486	arg1	trafficking					553:563	cell trafficking	548:563	cell trafficking	548:563	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	7	25	theme	rough	942:946	arg1	reticulum					962:970	the rough endoplasmatic reticulum	938:970	the rough endoplasmatic reticulum (ER) compartment	938:987	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	7	25	theme	rough	942:946	arg1	ER					973:974	ER	973:974	ER	973:974	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	6	26	theme	prME	766:769	arg1	constructs					771:780	ZIKV prME constructs	761:780	ZIKV prME constructs	761:780	Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions.
32842538	1	27	theme	protein	159:165	arg1	synthesis					167:175	protein synthesis	159:175	protein synthesis	159:175	Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification.
32842538	7	28	theme	protein	915:921	arg1	aggregation					923:933	protein aggregation	915:933	protein aggregation	915:933	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	6	29	theme	ZIKV	854:857	arg1	virions					859:865	ZIKV virions	854:865	ZIKV virions	854:865	Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions.
32842538	7	30	theme	endoplasmatic	948:960	arg1	reticulum					962:970	the rough endoplasmatic reticulum	938:970	the rough endoplasmatic reticulum (ER) compartment	938:987	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	7	30	theme	endoplasmatic	948:960	arg1	ER					973:974	ER	973:974	ER	973:974	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	9	31	theme	stress	1272:1277	arg1	protein					1250:1256	CCAAT-enhancer-binding protein homologous protein	1208:1256	CCAAT-enhancer-binding protein homologous protein (CHOP)	1208:1263	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	31	theme	stress	1272:1277	arg1	marker					1279:1284	an ER stress marker	1266:1284	an ER stress marker	1266:1284	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	2	32	theme	envelope	265:272	arg1	protein					278:284	envelope (E) protein	265:284	envelope (E) protein	265:284	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	32	theme	envelope	265:272	arg1	proteins					228:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	3	33	theme	glycosylation	369:381	arg1	site					383:386	a single N-linked glycosylation site	351:386	a single N-linked glycosylation site	351:386	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	0	34	theme	Pre-Membrane	23:34	arg1	Protein					36:42	the Pre-Membrane Protein	19:42	the Pre-Membrane Protein	19:42	N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle.
32842538	3	35	gly	glycosylation	369:381	arg2	site					383:386	a single N-linked glycosylation site	351:386	a single N-linked glycosylation site	351:386	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	3	36	from	site	431:434	arg1	protein					445:451	the E protein	439:451	the E protein	439:451	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	10	37	theme	protein	1411:1417	arg1	trafficking					1419:1429	viral protein trafficking	1405:1429	viral protein trafficking	1405:1429	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	2	38	theme	ZIKV	211:214	arg1	protein					278:284	envelope (E) protein	265:284	envelope (E) protein	265:284	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	38	theme	ZIKV	211:214	arg1	proteins					228:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	38	theme	ZIKV	211:214	arg1	pre-membrane					242:253	the pre-membrane	238:253	the pre-membrane (prM)	238:259	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	5	39	theme	infectious	706:715	arg1	virus					717:721	an infectious virus	703:721	an infectious virus	703:721	Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant.
32842538	10	40	theme	infectious	1356:1365	arg1	cycle					1367:1371	the ZIKV infectious cycle	1347:1371	the ZIKV infectious cycle	1347:1371	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	9	41	from	lack	1147:1150	arg1	prM					1171:1173	prM	1171:1173	prM	1171:1173	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	6	42	theme	effective	831:839	arg1	secretion					841:849	effective secretion	831:849	effective secretion of ZIKV virions	831:865	Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions.
32842538	2	43	gly	N-glycosylated	290:303	arg1	protein					278:284	envelope (E) protein	265:284	envelope (E) protein	265:284	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	43	gly	N-glycosylated	290:303	arg1	proteins					228:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	43	gly	N-glycosylated	290:303	arg1	pre-membrane					242:253	the pre-membrane	238:253	the pre-membrane (prM)	238:259	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	0	44	gly	N-glycosylation	0:14	arg1	Protein					36:42	the Pre-Membrane Protein	19:42	the Pre-Membrane Protein	19:42	N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle.
32842538	7	45	from	absence	872:878	arg1	E					906:906	E	906:906	E	906:906	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	7	45	from	absence	872:878	arg1	prM					899:901	prM	899:901	prM	899:901	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	9	46	theme	nuclear	1183:1189	arg1	translocation					1191:1203	nuclear translocation	1183:1203	nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker	1183:1284	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	3	47	theme	single	353:358	arg1	site					383:386	a single N-linked glycosylation site	351:386	a single N-linked glycosylation site	351:386	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	9	48	theme	CCAAT-enhancer-binding	1208:1229	arg1	marker					1279:1284	an ER stress marker	1266:1284	an ER stress marker	1266:1284	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	48	theme	CCAAT-enhancer-binding	1208:1229	arg1	CHOP					1259:1262	CHOP	1259:1262	CHOP	1259:1262	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	48	theme	CCAAT-enhancer-binding	1208:1229	arg1	protein					1250:1256	CCAAT-enhancer-binding protein homologous protein	1208:1256	CCAAT-enhancer-binding protein homologous protein (CHOP)	1208:1263	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	5	49	theme	prM/E-double	666:677	arg1	mutants					679:685	the prM/E-double mutants	662:685	the prM/E-double mutants	662:685	Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant.
32842538	8	50	theme	mutant	1056:1061	arg1	virus					1063:1067	the mutant virus	1052:1067	the mutant virus	1052:1067	The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization.
32842538	7	51	theme	N-glycan	887:894	arg1	absence					872:878	The absence	868:878	The absence of the N-glycan on prM or E	868:906	The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment.
32842538	4	52	theme	cell	548:551	arg1	trafficking					553:563	cell trafficking	548:563	cell trafficking	548:563	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	3	53	theme	strains	334:340	arg1	protein					314:320	The prM protein	306:320	The prM protein of all ZIKV strains	306:340	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	9	54	theme	protein	1231:1237	arg1	marker					1279:1284	an ER stress marker	1266:1284	an ER stress marker	1266:1284	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	54	theme	protein	1231:1237	arg1	CHOP					1259:1262	CHOP	1259:1262	CHOP	1259:1262	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	54	theme	protein	1231:1237	arg1	protein					1250:1256	CCAAT-enhancer-binding protein homologous protein	1208:1256	CCAAT-enhancer-binding protein homologous protein (CHOP)	1208:1263	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	1	55	link	-linked	102:108	arg1	glycosylation					118:130	Asparagine (N)-linked protein glycosylation	88:130	Asparagine (N)-linked protein glycosylation	88:130	Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification.
32842538	4	56	link	N-linked	501:508	arg1	glycosylation					510:522	prM and E N-linked glycosylation	491:522	prM and E N-linked glycosylation	491:522	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	2	57	theme	virus	204:208	arg1	protein					278:284	envelope (E) protein	265:284	envelope (E) protein	265:284	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	57	theme	virus	204:208	arg1	proteins					228:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	57	theme	virus	204:208	arg1	pre-membrane					242:253	the pre-membrane	238:253	the pre-membrane (prM)	238:259	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	3	58	theme	N-linked	422:429	arg1	site					431:434	an N-linked site	419:434	an N-linked site in the E protein	419:451	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	10	59	theme	protein	1432:1438	arg1	folding					1440:1446	protein folding	1432:1446	protein folding	1432:1446	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	9	60	theme	homologous	1239:1248	arg1	marker					1279:1284	an ER stress marker	1266:1284	an ER stress marker	1266:1284	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	60	theme	homologous	1239:1248	arg1	CHOP					1259:1262	CHOP	1259:1262	CHOP	1259:1262	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	9	60	theme	homologous	1239:1248	arg1	protein					1250:1256	CCAAT-enhancer-binding protein homologous protein	1208:1256	CCAAT-enhancer-binding protein homologous protein (CHOP)	1208:1263	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	10	61	theme	ZIKV	1351:1354	arg1	cycle					1367:1371	the ZIKV infectious cycle	1347:1371	the ZIKV infectious cycle	1347:1371	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	2	62	theme	Zika	199:202	arg1	protein					278:284	envelope (E) protein	265:284	envelope (E) protein	265:284	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	62	theme	Zika	199:202	arg1	proteins					228:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	62	theme	Zika	199:202	arg1	pre-membrane					242:253	the pre-membrane	238:253	the pre-membrane (prM)	238:259	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	9	63	theme	protein	1250:1256	arg1	translocation					1191:1203	nuclear translocation	1183:1203	nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker	1183:1284	In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker.
32842538	3	64	link	N-linked	422:429	arg1	site					431:434	an N-linked site	419:434	an N-linked site in the E protein	419:451	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	1	65	theme	-linked	102:108	arg1	glycosylation					118:130	Asparagine (N)-linked protein glycosylation	88:130	Asparagine (N)-linked protein glycosylation	88:130	Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification.
32842538	4	66	theme	glycosylation	510:522	arg1	impact					481:486	the impact	477:486	the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking	477:563	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	2	67	theme	E	275:275	arg1	protein					278:284	envelope (E) protein	265:284	envelope (E) protein	265:284	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	67	theme	E	275:275	arg1	proteins					228:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	4	68	theme	N-linked	501:508	arg1	glycosylation					510:522	prM and E N-linked glycosylation	491:522	prM and E N-linked glycosylation	491:522	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	0	69	theme	Zika	65:68	arg1	Cycle					81:85	the Zika Virus Life Cycle	61:85	the Zika Virus Life Cycle	61:85	N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle.
32842538	2	70	theme	structural	217:226	arg1	protein					278:284	envelope (E) protein	265:284	envelope (E) protein	265:284	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	70	theme	structural	217:226	arg1	proteins					228:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins	195:235	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	2	70	theme	structural	217:226	arg1	pre-membrane					242:253	the pre-membrane	238:253	the pre-membrane (prM)	238:259	Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated.
32842538	3	71	theme	E	443:443	arg1	protein					445:451	the E protein	439:451	the E protein	439:451	The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein.
32842538	4	72	theme	ZIKV	527:530	arg1	infectivity					532:542	ZIKV infectivity	527:542	ZIKV infectivity	527:542	Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking.
32842538	8	73	theme	ER-Golgi	1078:1085	arg1	ERGIC					1113:1117	ERGIC	1113:1117	ERGIC	1113:1117	The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization.
32842538	8	73	theme	ER-Golgi	1078:1085	arg1	compartment					1100:1110	ER-Golgi intermediate compartment	1078:1110	the ER-Golgi intermediate compartment (ERGIC) localization	1074:1131	The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization.
32842538	10	74	theme	viral	1405:1409	arg1	trafficking					1419:1429	viral protein trafficking	1405:1429	viral protein trafficking	1405:1429	To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
32842538	8	75	theme	compartment	1100:1110	arg1	localization					1120:1131	the ER-Golgi intermediate compartment (ERGIC) localization	1074:1131	the ER-Golgi intermediate compartment (ERGIC) localization	1074:1131	The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization.
34857845	0	0	from	structure	21:29	arg1	cirrhosis					67:75	liver cirrhosis	61:75	liver cirrhosis	61:75	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	6	1	theme	fucosylated	1222:1232	arg1	N-glycoforms					1234:1245	the core fucosylated N-glycoforms	1213:1245	the core fucosylated N-glycoforms	1213:1245	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	2	from	quantification	1195:1208	arg1	efficient					1163:1171	efficient	1163:1171	efficient	1163:1171	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	2	from	quantification	1195:1208	arg1	combination					1105:1115	a combination	1103:1115	a combination of soft fragmentation with exoglycosidases	1103:1158	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	5	3	attach	derived	1008:1014	arg2	glycoforms					997:1006	their nonfucosylated glycoforms	976:1006	their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	976:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	3	attach	derived	1008:1014	arg1	proteins					1030:1037	18 serum proteins	1021:1037	18 serum proteins in liver disease of different etiologies	1021:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	1	4	theme	macromolecules	191:204	arg1	groups					170:175	the major groups	160:175	the major groups of biological macromolecules in living organisms	160:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	1	4	theme	macromolecules	191:204	arg1	macromolecules					191:204	biological macromolecules	180:204	biological macromolecules in living organisms	180:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	5	5	gly	glycopeptides	959:971	arg2	glycopeptides					959:971	45 glycopeptides	956:971	45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	956:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	6	theme	core	742:745	arg1	fucosylation					747:758	the core fucosylation	738:758	the core fucosylation of proteins	738:770	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	6	7	from	assignment	1180:1189	arg1	efficient					1163:1171	efficient	1163:1171	efficient	1163:1171	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	7	from	assignment	1180:1189	arg1	combination					1105:1115	a combination	1103:1115	a combination of soft fragmentation with exoglycosidases	1103:1158	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	1	8	theme	living	209:214	arg1	organisms					216:224	living organisms	209:224	living organisms	209:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	5	9	theme	glycans	814:820	arg1	resolution					796:805	partial structural resolution	777:805	partial structural resolution of the glycans	777:820	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	0	10	from	cirrhosis	67:75	arg1	Analysis					0:7	Analysis	0:7	Analysis of site and structure specific core fucosylation in liver cirrhosis	0:75	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	2	11	theme	protein	263:269	arg1	folding					271:277	protein folding	263:277	protein folding	263:277	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	5	12	theme	glycopeptides	959:971	arg1	glycoforms					942:951	the core fucosylated glycoforms	921:951	the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	921:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	13	theme	structural	785:794	arg1	resolution					796:805	partial structural resolution	777:805	partial structural resolution of the glycans	777:820	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	1	14	from	organisms	216:224	arg1	groups					170:175	the major groups	160:175	the major groups of biological macromolecules in living organisms	160:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	1	14	from	organisms	216:224	arg1	macromolecules					191:204	biological macromolecules	180:204	biological macromolecules in living organisms	180:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	6	15	with	combination	1105:1115	arg1	exoglycosidases					1144:1158	exoglycosidases	1144:1158	exoglycosidases	1144:1158	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	8	16	theme	Further	1458:1464	arg1	studies					1466:1472	Further studies	1458:1472	Further studies	1458:1472	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	4	17	gly	N-glycopeptides	593:607	arg2	N-glycopeptides					593:607	core fucosylated N-glycopeptides	576:607	core fucosylated N-glycopeptides	576:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	5	18	theme	spectrometric	857:869	arg1	analysis					886:893	the mass spectrometric SWATH-type DIA analysis	848:893	the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	848:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	19	theme	fucosylated	930:940	arg1	glycoforms					942:951	the core fucosylated glycoforms	921:951	the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	921:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	1	20	theme	major	164:168	arg1	groups					170:175	the major groups	160:175	the major groups of biological macromolecules in living organisms	160:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	1	20	theme	major	164:168	arg1	macromolecules					191:204	biological macromolecules	180:204	biological macromolecules in living organisms	180:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	6	21	theme	fragmentation	1125:1137	arg1	efficient					1163:1171	efficient	1163:1171	efficient	1163:1171	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	21	theme	fragmentation	1125:1137	arg1	combination					1105:1115	a combination	1103:1115	a combination of soft fragmentation with exoglycosidases	1103:1158	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	0	22	from	site	12:15	arg1	cirrhosis					67:75	liver cirrhosis	61:75	liver cirrhosis	61:75	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	6	23	gly	N-glycoforms	1234:1245	arg1	core					1217:1220	the core fucosylated N-glycoforms	1213:1245	the core fucosylated N-glycoforms	1213:1245	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	5	24	theme	DIA	882:884	arg1	analysis					886:893	the mass spectrometric SWATH-type DIA analysis	848:893	the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	848:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	1	25	from	groups	170:175	arg1	organisms					216:224	living organisms	209:224	living organisms	209:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	5	26	theme	serum	1024:1028	arg1	proteins					1030:1037	18 serum proteins	1021:1037	18 serum proteins in liver disease of different etiologies	1021:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	3	27	theme	such	399:402	arg1	processes					404:412	such processes	399:412	such processes	399:412	Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer.
34857845	0	28	from	Analysis	0:7	arg1	cirrhosis					67:75	liver cirrhosis	61:75	liver cirrhosis	61:75	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	0	29	theme	exoglycosidase-assisted	83:105	arg1	LC-MS/MS					124:131	exoglycosidase-assisted data-independent LC-MS/MS	83:131	exoglycosidase-assisted data-independent LC-MS/MS	83:131	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	7	30	gly	fucosylated	1437:1447	arg1	glycans					1449:1455	the core fucosylated glycans	1428:1455	the core fucosylated glycans	1428:1455	In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans.
34857845	3	31	theme	proteins	380:387	arg1	Fucosylation					364:375	Fucosylation	364:375	Fucosylation of proteins	364:387	Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer.
34857845	6	32	dep	assignment	1180:1189	arg1	the					1176:1178	the	1176:1178	the	1176:1178	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	7	33	theme	disease-associated	1323:1340	arg1	changes					1342:1348	disease-associated changes	1323:1348	disease-associated changes in core fucosylation	1323:1369	In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans.
34857845	5	34	theme	analysis	886:893	arg1	results					837:843	results	837:843	results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	837:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	4	35	theme	glycans	556:562	arg1	glycans					556:562	fucosylated glycans	544:562	fucosylated glycans	544:562	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	4	35	theme	glycans	556:562	arg1	N-glycopeptides					593:607	core fucosylated N-glycopeptides	576:607	core fucosylated N-glycopeptides	576:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	4	35	theme	glycans	556:562	arg1	sites					567:571	sites	567:571	sites of core fucosylated N-glycopeptides	567:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	4	35	theme	glycans	556:562	arg1	structures					530:539	structures	530:539	structures of fucosylated glycans	530:562	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	0	36	theme	liver	61:65	arg1	cirrhosis					67:75	liver cirrhosis	61:75	liver cirrhosis	61:75	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	8	37	theme	core	1528:1531	arg1	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	37	theme	core	1528:1531	arg1	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	5	38	from	proteins	1030:1037	arg1	disease					1048:1054	liver disease	1042:1054	liver disease of different etiologies	1042:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	39	theme	different	1059:1067	arg1	etiologies					1069:1078	different etiologies	1059:1078	different etiologies	1059:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	0	40	theme	site	12:15	arg1	Analysis					0:7	Analysis	0:7	Analysis of site and structure specific core fucosylation in liver cirrhosis	0:75	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	0	41	theme	structure	21:29	arg1	Analysis					0:7	Analysis	0:7	Analysis of site and structure specific core fucosylation in liver cirrhosis	0:75	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	7	42	theme	glycans	1449:1455	arg1	branching					1415:1423	branching	1415:1423	branching of the core fucosylated glycans	1415:1455	In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans.
34857845	3	43	theme	various	437:443	arg1	diseases					445:452	various diseases	437:452	various diseases including autoimmunity and cancer	437:486	Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer.
34857845	3	43	theme	various	437:443	arg1	cancer					481:486	cancer	481:486	cancer	481:486	Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer.
34857845	3	43	theme	various	437:443	arg1	autoimmunity					464:475	autoimmunity	464:475	autoimmunity	464:475	Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer.
34857845	4	44	theme	N-glycopeptides	593:607	arg1	glycans					556:562	fucosylated glycans	544:562	fucosylated glycans	544:562	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	4	44	theme	N-glycopeptides	593:607	arg1	N-glycopeptides					593:607	core fucosylated N-glycopeptides	576:607	core fucosylated N-glycopeptides	576:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	4	44	theme	N-glycopeptides	593:607	arg1	sites					567:571	sites	567:571	sites of core fucosylated N-glycopeptides	567:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	4	44	theme	N-glycopeptides	593:607	arg1	structures					530:539	structures	530:539	structures of fucosylated glycans	530:562	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	5	45	gly	fucosylated	930:940	arg1	glycoforms					942:951	the core fucosylated glycoforms	921:951	the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	921:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	45	gly	fucosylated	930:940	arg1	glycopeptides					959:971	45 glycopeptides	956:971	45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	956:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	8	46	used	used	1568:1571	arg2	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	46	used	used	1568:1571	arg2	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	5	47	theme	abundances	907:916	arg1	analysis					886:893	the mass spectrometric SWATH-type DIA analysis	848:893	the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	848:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	8	48	gly	fucosylated	1533:1543	arg1	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	48	gly	fucosylated	1533:1543	arg1	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	3	49	gly	Fucosylation	364:375	arg1	proteins					380:387	proteins	380:387	proteins	380:387	Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer.
34857845	7	50	theme	core	1432:1435	arg1	glycans					1449:1455	the core fucosylated glycans	1428:1455	the core fucosylated glycans	1428:1455	In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans.
34857845	5	51	dep	facilitate	702:711	arg1	experiments					685:695	experiments	685:695	experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	685:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	2	52	theme	Many	227:230	arg1	stability					280:288	stability	280:288	stability	280:288	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	52	theme	Many	227:230	arg1	processes					243:251	Many biological processes	227:251	Many biological processes including protein folding, stability, immune response, and receptor activation	227:330	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	52	theme	Many	227:230	arg1	folding					271:277	protein folding	263:277	protein folding	263:277	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	52	theme	Many	227:230	arg1	response					298:305	immune response	291:305	immune response	291:305	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	52	theme	Many	227:230	arg1	activation					321:330	receptor activation	312:330	receptor activation	312:330	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	0	53	dep	site	12:15	arg1	fucosylation					45:56	specific core fucosylation	31:56	specific core fucosylation	31:56	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	6	54	theme	specific	1250:1257	arg1	sites					1259:1263	specific sites	1250:1263	specific sites of protein attachment	1250:1285	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	54	theme	specific	1250:1257	arg1	attachment					1276:1285	protein attachment	1268:1285	protein attachment	1268:1285	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	8	55	theme	disease	1593:1599	arg1	progression					1601:1611	liver disease progression	1587:1611	liver disease progression	1587:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	6	56	theme	N-glycoforms	1234:1245	arg1	quantification					1195:1208	quantification	1195:1208	quantification	1195:1208	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	56	theme	N-glycoforms	1234:1245	arg1	assignment					1180:1189	assignment	1180:1189	assignment	1180:1189	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	7	57	theme	core	1353:1356	arg1	fucosylation					1358:1369	core fucosylation	1353:1369	core fucosylation	1353:1369	In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans.
34857845	5	58	theme	fucosylation	747:758	arg1	analysis					726:733	quantitative analysis	713:733	quantitative analysis of the core fucosylation of proteins	713:770	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	6	59	theme	core	1217:1220	arg1	N-glycoforms					1234:1245	the core fucosylated N-glycoforms	1213:1245	the core fucosylated N-glycoforms	1213:1245	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	5	60	theme	proteins	763:770	arg1	fucosylation					747:758	the core fucosylation	738:758	the core fucosylation of proteins	738:770	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	2	61	theme	receptor	312:319	arg1	activation					321:330	receptor activation	312:330	receptor activation	312:330	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	5	62	gly	nonfucosylated	982:995	arg1	glycoforms					997:1006	their nonfucosylated glycoforms	976:1006	their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	976:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	1	63	theme	biological	180:189	arg1	macromolecules					191:204	biological macromolecules	180:204	biological macromolecules in living organisms	180:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	0	64	theme	core	40:43	arg1	fucosylation					45:56	specific core fucosylation	31:56	specific core fucosylation	31:56	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	5	65	gly	glycoforms	942:951	arg1	glycopeptides					959:971	45 glycopeptides	956:971	45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	956:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	65	gly	glycoforms	942:951	arg1	core					925:928	the core fucosylated glycoforms	921:951	the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	921:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	66	gly	fucosylation	747:758	arg1	proteins					763:770	proteins	763:770	proteins	763:770	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	4	67	gly	fucosylated	581:591	arg1	N-glycopeptides					593:607	core fucosylated N-glycopeptides	576:607	core fucosylated N-glycopeptides	576:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	5	68	theme	nonfucosylated	982:995	arg1	glycoforms					997:1006	their nonfucosylated glycoforms	976:1006	their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	976:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	4	69	gly	fucosylated	544:554	arg1	glycans					556:562	fucosylated glycans	544:562	fucosylated glycans	544:562	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	5	70	theme	glycoforms	942:951	arg1	abundances					907:916	relative abundances	898:916	relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	898:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	6	71	theme	attachment	1276:1285	arg1	sites					1259:1263	specific sites	1250:1263	specific sites of protein attachment	1250:1285	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	71	theme	attachment	1276:1285	arg1	attachment					1276:1285	protein attachment	1268:1285	protein attachment	1268:1285	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	7	72	from	changes	1342:1348	arg1	fucosylation					1358:1369	core fucosylation	1353:1369	core fucosylation	1353:1369	In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans.
34857845	5	73	theme	partial	777:783	arg1	resolution					796:805	partial structural resolution	777:805	partial structural resolution of the glycans	777:820	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	4	74	gly	glycopeptides	635:647	arg2	glycopeptides					635:647	the glycopeptides	631:647	the glycopeptides	631:647	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	4	75	theme	core	576:579	arg1	N-glycopeptides					593:607	core fucosylated N-glycopeptides	576:607	core fucosylated N-glycopeptides	576:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	2	76	theme	immune	291:296	arg1	response					298:305	immune response	291:305	immune response	291:305	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	5	77	theme	liver	1042:1046	arg1	disease					1048:1054	liver disease	1042:1054	liver disease of different etiologies	1042:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	4	78	theme	Mass	489:492	arg1	spectrometry					494:505	Mass spectrometry	489:505	Mass spectrometry	489:505	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	5	79	theme	mass	852:855	arg1	analysis					886:893	the mass spectrometric SWATH-type DIA analysis	848:893	the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	848:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	80	theme	SWATH-type	871:880	arg1	analysis					886:893	the mass spectrometric SWATH-type DIA analysis	848:893	the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	848:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	1	81	from	macromolecules	191:204	arg1	organisms					216:224	living organisms	209:224	living organisms	209:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	1	82	theme	groups	170:175	arg1	one					153:155	one	153:155	one	153:155	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	1	82	theme	groups	170:175	arg1	groups					170:175	the major groups	160:175	the major groups of biological macromolecules in living organisms	160:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	1	82	theme	groups	170:175	arg1	macromolecules					191:204	biological macromolecules	180:204	biological macromolecules in living organisms	180:224	Carbohydrates form one of the major groups of biological macromolecules in living organisms.
34857845	6	83	theme	soft	1120:1123	arg1	fragmentation					1125:1137	soft fragmentation	1120:1137	soft fragmentation	1120:1137	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	4	84	theme	fucosylated	581:591	arg1	N-glycopeptides					593:607	core fucosylated N-glycopeptides	576:607	core fucosylated N-glycopeptides	576:607	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	0	85	theme	data-independent	107:122	arg1	LC-MS/MS					124:131	exoglycosidase-assisted data-independent LC-MS/MS	83:131	exoglycosidase-assisted data-independent LC-MS/MS	83:131	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	4	86	theme	fucosylated	544:554	arg1	glycans					556:562	fucosylated glycans	544:562	fucosylated glycans	544:562	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	6	87	gly	fucosylated	1222:1232	arg1	N-glycoforms					1234:1245	the core fucosylated N-glycoforms	1213:1245	the core fucosylated N-glycoforms	1213:1245	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	5	88	theme	quantitative	713:724	arg1	analysis					726:733	quantitative analysis	713:733	quantitative analysis of the core fucosylation of proteins	713:770	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	8	89	theme	tri-	1503:1506	arg1	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	89	theme	tri-	1503:1506	arg1	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	4	90	theme	glycopeptides	635:647	arg1	quantification					613:626	quantification	613:626	quantification of the glycopeptides	613:647	Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored.
34857845	8	91	theme	tetra-antennary	1512:1526	arg1	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	91	theme	tetra-antennary	1512:1526	arg1	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	92	theme	progression	1601:1611	arg1	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	92	theme	progression	1601:1611	arg1	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	5	93	theme	core	925:928	arg1	glycoforms					942:951	the core fucosylated glycoforms	921:951	the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	921:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	5	94	theme	etiologies	1069:1078	arg1	disease					1048:1054	liver disease	1042:1054	liver disease of different etiologies	1042:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	8	95	theme	fucosylated	1533:1543	arg1	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	95	theme	fucosylated	1533:1543	arg1	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	0	96	theme	specific	31:38	arg1	fucosylation					45:56	specific core fucosylation	31:56	specific core fucosylation	31:56	Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS.
34857845	7	97	theme	fucosylated	1437:1447	arg1	glycans					1449:1455	the core fucosylated glycans	1428:1455	the core fucosylated glycans	1428:1455	In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans.
34857845	6	98	from	sites	1259:1263	arg1	quantification					1195:1208	quantification	1195:1208	quantification	1195:1208	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	6	98	from	sites	1259:1263	arg1	assignment					1180:1189	assignment	1180:1189	assignment	1180:1189	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	5	99	theme	relative	898:905	arg1	abundances					907:916	relative abundances	898:916	relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies	898:1078	We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies.
34857845	6	100	theme	protein	1268:1274	arg1	attachment					1276:1285	protein attachment	1268:1285	protein attachment	1268:1285	Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment.
34857845	2	101	theme	biological	232:241	arg1	stability					280:288	stability	280:288	stability	280:288	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	101	theme	biological	232:241	arg1	processes					243:251	Many biological processes	227:251	Many biological processes including protein folding, stability, immune response, and receptor activation	227:330	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	101	theme	biological	232:241	arg1	folding					271:277	protein folding	263:277	protein folding	263:277	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	101	theme	biological	232:241	arg1	response					298:305	immune response	291:305	immune response	291:305	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	2	101	theme	biological	232:241	arg1	activation					321:330	receptor activation	312:330	receptor activation	312:330	Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation.
34857845	8	102	gly	glycopeptides	1545:1557	arg2	glycopeptides					1545:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	tri- and tetra-antennary core fucosylated glycopeptides	1503:1557	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	102	gly	glycopeptides	1545:1557	arg2	markers					1576:1582	markers	1576:1582	markers of liver disease progression	1576:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
34857845	8	103	theme	liver	1587:1591	arg1	progression					1601:1611	liver disease progression	1587:1611	liver disease progression	1587:1611	Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
33577335	0	0	from	Functions	17:25	arg1	Glycoforms					96:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	0	0	from	Functions	17:25	arg1	Based					52:56	Human Interleukin-17A Based	30:56	Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms	30:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	3	1	gly	glycosylated	470:481	arg1	IL-17A					500:505	IL-17A	500:505	IL-17A	500:505	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	1	gly	glycosylated	470:481	arg1	interleukin-17A					483:497	homogeneously glycosylated interleukin-17A	456:497	homogeneously glycosylated interleukin-17A (IL-17A)	456:506	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	6	2	theme	exchange	1173:1180	arg1	spectroscopic					1187:1199	hydrogen/deuterium exchange mass spectroscopic	1154:1199	hydrogen/deuterium exchange mass spectroscopic	1154:1199	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	0	3	theme	Homogeneous	84:94	arg1	Glycoforms					96:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	3	4	from	synthesis	561:569	arg1	segments					629:636	segments	629:636	segments	629:636	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	4	5	theme	N-glycans	757:765	arg1	role					749:752	the stabilizing role	733:752	the stabilizing role of N-glycans during the folding step	733:789	The obtained homogeneous glycoproteins allow for the demonstration of the stabilizing role of N-glycans during the folding step.
33577335	5	6	with	glycoform	964:972	arg1	undecasaccharides					986:1002	sialyl undecasaccharides	979:1002	sialyl undecasaccharides	979:1002	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	5	7	theme	GlcNAc-modified	1084:1098	arg1	proteins					1100:1107	the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins	1057:1107	the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins	1057:1107	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	5	8	gly	glycoforms	821:830	arg1	IL-17A					814:819	three IL-17A glycoforms	808:830	three IL-17A glycoforms	808:830	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	6	9	theme	surface	1118:1124	arg1	SPR					1145:1147	SPR	1145:1147	SPR	1145:1147	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	6	9	theme	surface	1118:1124	arg1	resonance					1134:1142	surface plasmon resonance	1118:1142	surface plasmon resonance (SPR)	1118:1148	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	5	10	theme	weaker	1018:1023	arg1	effect					1037:1042	much weaker stimulatory effect	1013:1042	much weaker stimulatory effect	1013:1042	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	3	11	theme	chemoenzymatic	591:604	arg1	modification					613:624	chemoenzymatic glycan modification	591:624	chemoenzymatic glycan modification on segments	591:636	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	2	12	theme	methods	321:327	arg1	lack					286:289	the lack	282:289	the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans	282:406	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	1	13	theme	essential	138:146	arg1	type					148:151	an essential type	135:151	an essential type of posttranslational modification for proteins	135:198	N-Glycosylation represents an essential type of posttranslational modification for proteins.
33577335	4	14	gly	glycoproteins	688:700	arg1	glycoproteins					688:700	The obtained homogeneous glycoproteins	663:700	The obtained homogeneous glycoproteins	663:700	The obtained homogeneous glycoproteins allow for the demonstration of the stabilizing role of N-glycans during the folding step.
33577335	6	15	theme	plasmon	1126:1132	arg1	SPR					1145:1147	SPR	1145:1147	SPR	1145:1147	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	6	15	theme	plasmon	1126:1132	arg1	resonance					1134:1142	surface plasmon resonance	1118:1142	surface plasmon resonance (SPR)	1118:1148	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	2	16	theme	biochemical	309:319	arg1	methods					321:327	analytical and biochemical methods	294:327	analytical and biochemical methods	294:327	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	4	17	theme	stabilizing	737:747	arg1	role					749:752	the stabilizing role	733:752	the stabilizing role of N-glycans during the folding step	733:789	The obtained homogeneous glycoproteins allow for the demonstration of the stabilizing role of N-glycans during the folding step.
33577335	5	18	theme	human	844:848	arg1	assay					875:879	a normal human dermal fibroblast (NHDF) assay	835:879	a normal human dermal fibroblast (NHDF) assay	835:879	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	6	19	theme	mass	1182:1185	arg1	spectroscopic					1187:1199	hydrogen/deuterium exchange mass spectroscopic	1154:1199	hydrogen/deuterium exchange mass spectroscopic	1154:1199	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	5	20	theme	normal	837:842	arg1	assay					875:879	a normal human dermal fibroblast (NHDF) assay	835:879	a normal human dermal fibroblast (NHDF) assay	835:879	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	3	21	theme	peptides	581:588	arg1	modification					613:624	chemoenzymatic glycan modification	591:624	chemoenzymatic glycan modification on segments	591:636	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	21	theme	peptides	581:588	arg1	ligations					652:660	chemical ligations	643:660	chemical ligations	643:660	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	21	theme	peptides	581:588	arg1	synthesis					561:569	solid-phase synthesis	549:569	solid-phase synthesis of (glyco)peptides	549:588	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	6	22	theme	receptor	1305:1312	arg1	IL-17RA					1314:1320	its receptor IL-17RA	1301:1320	its receptor IL-17RA	1301:1320	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	0	23	theme	N-Glycan	8:15	arg1	Functions					17:25	N-Glycan Functions	8:25	N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms	8:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	5	24	theme	IL-17A	814:819	arg1	glycoforms					821:830	three IL-17A glycoforms	808:830	three IL-17A glycoforms	808:830	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	2	25	theme	protein	361:367	arg1	glycoforms					369:378	the protein glycoforms	357:378	the protein glycoforms with various intact glycans	357:406	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	0	26	from	Based	52:56	arg1	Glycoforms					96:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	3	27	theme	interleukin-17A	483:497	arg1	synthesis					428:436	our synthesis	424:436	our synthesis	424:436	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	27	theme	interleukin-17A	483:497	arg1	evaluation					442:451	evaluation	442:451	evaluation	442:451	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	5	28	theme	NHDF	869:872	arg1	assay					875:879	a normal human dermal fibroblast (NHDF) assay	835:879	a normal human dermal fibroblast (NHDF) assay	835:879	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	5	29	theme	stimulatory	1025:1035	arg1	effect					1037:1042	much weaker stimulatory effect	1013:1042	much weaker stimulatory effect	1013:1042	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	7	30	gly	glycoproteins	1369:1381	arg1	glycoproteins					1369:1381	glycoproteins	1369:1381	glycoproteins	1369:1381	This structure-activity relationship study on glycoproteins highlights the viability of applying the de novo approach to probe the roles of N-glycans.
33577335	4	31	theme	folding	778:784	arg1	step					786:789	the folding step	774:789	the folding step	774:789	The obtained homogeneous glycoproteins allow for the demonstration of the stabilizing role of N-glycans during the folding step.
33577335	3	32	theme	glycan	606:611	arg1	modification					613:624	chemoenzymatic glycan modification	591:624	chemoenzymatic glycan modification on segments	591:636	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	33	theme	chemical	643:650	arg1	ligations					652:660	chemical ligations	643:660	chemical ligations	643:660	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	6	34	theme	resonance	1134:1142	arg1	experiments					1201:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments	1110:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments	1110:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	6	35	theme	type	1248:1251	arg1	N-glycan					1253:1260	the evaluated complex type N-glycan	1226:1260	the evaluated complex type N-glycan	1226:1260	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	0	36	from	Glycoforms	96:105	arg1	Functions					17:25	N-Glycan Functions	8:25	N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms	8:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	6	37	theme	hydrogen/deuterium	1154:1171	arg1	spectroscopic					1187:1199	hydrogen/deuterium exchange mass spectroscopic	1154:1199	hydrogen/deuterium exchange mass spectroscopic	1154:1199	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	7	38	from	study	1360:1364	arg1	glycoproteins					1369:1381	glycoproteins	1369:1381	glycoproteins	1369:1381	This structure-activity relationship study on glycoproteins highlights the viability of applying the de novo approach to probe the roles of N-glycans.
33577335	5	39	theme	dose-dependent	889:902	arg1	wherein					952:958	wherein	952:958	wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins	952:1107	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	5	39	theme	dose-dependent	889:902	arg1	activities					927:936	dose-dependent interleukin-6-inducing activities	889:936	dose-dependent interleukin-6-inducing activities in all cases	889:949	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	0	40	theme	Interleukin-17A	36:50	arg1	Based					52:56	Human Interleukin-17A Based	30:56	Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms	30:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	3	41	theme	solid-phase	549:559	arg1	synthesis					561:569	solid-phase synthesis	549:569	solid-phase synthesis of (glyco)peptides	549:588	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	2	42	with	glycoforms	369:378	arg1	glycans					400:406	various intact glycans	385:406	various intact glycans	385:406	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	3	43	mod	modification	613:624	arg3	glycan					606:611	chemoenzymatic glycan modification	591:624	chemoenzymatic glycan modification on segments	591:636	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	43	mod	modification	613:624	arg1	peptides					581:588	(glyco)peptides	574:588	(glyco)peptides	574:588	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	44	from	ligations	652:660	arg1	segments					629:636	segments	629:636	segments	629:636	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	5	45	theme	interleukin-6-inducing	904:925	arg1	wherein					952:958	wherein	952:958	wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins	952:1107	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	5	45	theme	interleukin-6-inducing	904:925	arg1	activities					927:936	dose-dependent interleukin-6-inducing activities	889:936	dose-dependent interleukin-6-inducing activities in all cases	889:949	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	0	46	theme	Human	30:34	arg1	Based					52:56	Human Interleukin-17A Based	30:56	Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms	30:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	3	47	theme	glycosylated	470:481	arg1	IL-17A					500:505	IL-17A	500:505	IL-17A	500:505	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	47	theme	glycosylated	470:481	arg1	interleukin-17A					483:497	homogeneously glycosylated interleukin-17A	456:497	homogeneously glycosylated interleukin-17A (IL-17A)	456:506	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	2	48	theme	due	275:277	arg1	challenge					265:273	a challenge	263:273	a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans	263:406	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	6	49	theme	Further	1110:1116	arg1	experiments					1201:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments	1110:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments	1110:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	5	50	theme	dermal	850:855	arg1	assay					875:879	a normal human dermal fibroblast (NHDF) assay	835:879	a normal human dermal fibroblast (NHDF) assay	835:879	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	6	51	theme	spectroscopic	1187:1199	arg1	experiments					1201:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments	1110:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments	1110:1211	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	5	52	from	comparison	794:803	arg1	assay					875:879	a normal human dermal fibroblast (NHDF) assay	835:879	a normal human dermal fibroblast (NHDF) assay	835:879	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	5	53	from	activities	927:936	arg1	cases					945:949	all cases	941:949	all cases	941:949	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	2	54	theme	intact	393:398	arg1	glycans					400:406	various intact glycans	385:406	various intact glycans	385:406	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	5	55	theme	fibroblast	857:866	arg1	assay					875:879	a normal human dermal fibroblast (NHDF) assay	835:879	a normal human dermal fibroblast (NHDF) assay	835:879	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	6	56	theme	complex	1240:1246	arg1	N-glycan					1253:1260	the evaluated complex type N-glycan	1226:1260	the evaluated complex type N-glycan	1226:1260	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	2	57	theme	various	385:391	arg1	glycans					400:406	various intact glycans	385:406	various intact glycans	385:406	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	2	58	gly	glycoforms	369:378	arg1	protein					361:367	the protein glycoforms	357:378	the protein glycoforms with various intact glycans	357:406	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	2	59	theme	N-glycosylation	239:253	arg1	functions					226:234	the functions	222:234	the functions of N-glycosylation	222:253	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	2	60	theme	analytical	294:303	arg1	methods					321:327	analytical and biochemical methods	294:327	analytical and biochemical methods	294:327	However, deciphering the functions of N-glycosylation remains a challenge due to the lack of analytical and biochemical methods to accurately differentiate the protein glycoforms with various intact glycans.
33577335	4	61	theme	role	749:752	arg1	demonstration					716:728	the demonstration	712:728	the demonstration of the stabilizing role of N-glycans during the folding step	712:789	The obtained homogeneous glycoproteins allow for the demonstration of the stabilizing role of N-glycans during the folding step.
33577335	3	62	theme	synthetic	520:528	arg1	approach					530:537	a synthetic approach	518:537	a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations	518:660	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	3	63	from	modification	613:624	arg1	segments					629:636	segments	629:636	segments	629:636	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	5	64	theme	GlcNAc-	1061:1067	arg1	proteins					1100:1107	the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins	1057:1107	the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins	1057:1107	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	5	65	theme	sialyl	979:984	arg1	undecasaccharides					986:1002	sialyl undecasaccharides	979:1002	sialyl undecasaccharides	979:1002	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	7	66	theme	N-glycans	1463:1471	arg1	roles					1454:1458	the roles	1450:1458	the roles of N-glycans	1450:1471	This structure-activity relationship study on glycoproteins highlights the viability of applying the de novo approach to probe the roles of N-glycans.
33577335	1	67	theme	posttranslational	156:172	arg1	modification					174:185	posttranslational modification	156:185	posttranslational modification for proteins	156:198	N-Glycosylation represents an essential type of posttranslational modification for proteins.
33577335	0	68	theme	Synthesized	72:82	arg1	Glycoforms					96:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Chemically Synthesized Homogeneous Glycoforms	61:105	Probing N-Glycan Functions in Human Interleukin-17A Based on Chemically Synthesized Homogeneous Glycoforms.
33577335	5	69	dep	wherein	952:958	arg1	displays					1004:1011	displays	1004:1011	displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins	1004:1107	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	7	70	dep	de	1424:1425	arg1	novo					1427:1430	novo	1427:1430	novo	1427:1430	This structure-activity relationship study on glycoproteins highlights the viability of applying the de novo approach to probe the roles of N-glycans.
33577335	7	71	theme	de	1424:1425	arg1	approach					1432:1439	the de novo approach	1420:1439	the de novo approach to probe the roles of N-glycans	1420:1471	This structure-activity relationship study on glycoproteins highlights the viability of applying the de novo approach to probe the roles of N-glycans.
33577335	1	72	theme	modification	174:185	arg1	type					148:151	an essential type	135:151	an essential type of posttranslational modification for proteins	135:198	N-Glycosylation represents an essential type of posttranslational modification for proteins.
33577335	7	73	theme	structure-activity	1328:1345	arg1	relationship					1347:1358	This structure-activity relationship	1323:1358	This structure-activity relationship study on glycoproteins	1323:1381	This structure-activity relationship study on glycoproteins highlights the viability of applying the de novo approach to probe the roles of N-glycans.
33577335	4	74	theme	homogeneous	676:686	arg1	glycoproteins					688:700	The obtained homogeneous glycoproteins	663:700	The obtained homogeneous glycoproteins	663:700	The obtained homogeneous glycoproteins allow for the demonstration of the stabilizing role of N-glycans during the folding step.
33577335	5	75	theme	glycoforms	821:830	arg1	comparison					794:803	A comparison	792:803	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay	792:879	A comparison of three IL-17A glycoforms in a normal human dermal fibroblast (NHDF) assay reveals dose-dependent interleukin-6-inducing activities in all cases, wherein the glycoform with sialyl undecasaccharides displays much weaker stimulatory effect than that of the GlcNAc- or GlcNAc(β1→4)GlcNAc-modified proteins.
33577335	6	76	theme	evaluated	1230:1238	arg1	N-glycan					1253:1260	the evaluated complex type N-glycan	1226:1260	the evaluated complex type N-glycan	1226:1260	Further surface plasmon resonance (SPR) and hydrogen/deuterium exchange mass spectroscopic experiments confirm that the evaluated complex type N-glycan impedes the binding between IL-17A and its receptor IL-17RA.
33577335	3	77	theme	glyco	575:579	arg1	peptides					581:588	(glyco)peptides	574:588	(glyco)peptides	574:588	Here we report our synthesis and evaluation of homogeneously glycosylated interleukin-17A (IL-17A), based on a synthetic approach combining solid-phase synthesis of (glyco)peptides, chemoenzymatic glycan modification on segments, and chemical ligations.
33577335	7	78	theme	relationship	1347:1358	arg1	study					1360:1364	This structure-activity relationship study	1323:1364	This structure-activity relationship study on glycoproteins	1323:1381	This structure-activity relationship study on glycoproteins highlights the viability of applying the de novo approach to probe the roles of N-glycans.
33577335	4	79	theme	obtained	667:674	arg1	glycoproteins					688:700	The obtained homogeneous glycoproteins	663:700	The obtained homogeneous glycoproteins	663:700	The obtained homogeneous glycoproteins allow for the demonstration of the stabilizing role of N-glycans during the folding step.
33154157	7	0	theme	dengue	1379:1384	arg1	viruses					1386:1392	dengue viruses	1379:1392	dengue viruses in cellular models	1379:1411	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	5	1	with	MANEA	928:932	arg1	inhibitors					971:980	substrate-derived inhibitors	953:980	substrate-derived inhibitors	953:980	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	2	2	theme	Golgi	360:364	arg1	apparatus					366:374	Golgi apparatus	360:374	Golgi apparatus	360:374	N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases.
33154157	0	3	theme	host-glycosylation	64:81	arg1	Structure					0:8	Structure	0:8	Structure of human endo-α-1,2-mannosidase (MANEA)	0:48	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	0	3	theme	host-glycosylation	64:81	arg1	target					83:88	an antiviral host-glycosylation target	51:88	an antiviral host-glycosylation target	51:88	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	8	4	theme	glycosylation	1581:1593	arg1	biology					1560:1566	the biology	1556:1566	the biology of mammalian glycosylation	1556:1593	These results may contribute to efforts aimed at developing broad-spectrum antiviral agents and help provide a more in-depth understanding of the biology of mammalian glycosylation.
33154157	5	5	theme	MANEA	928:932	arg1	MANEA					928:932	human MANEA	922:932	human MANEA	922:932	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	5	5	theme	MANEA	928:932	arg1	complexes					938:946	complexes	938:946	complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding	938:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	5	5	theme	MANEA	928:932	arg1	domain					912:917	the catalytic domain	898:917	the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding	898:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	1	6	theme	quality	170:176	arg1	control					178:184	quality control	170:184	quality control	170:184	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	8	7	theme	mammalian	1571:1579	arg1	glycosylation					1581:1593	mammalian glycosylation	1571:1593	mammalian glycosylation	1571:1593	These results may contribute to efforts aimed at developing broad-spectrum antiviral agents and help provide a more in-depth understanding of the biology of mammalian glycosylation.
33154157	6	8	theme	substrate	1133:1141	arg1	preference					1143:1152	its substrate preference	1129:1152	its substrate preference	1129:1152	We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis.
33154157	3	9	theme	ER	672:673	arg1	glucosidases					675:686	ER glucosidases I and II	672:695	ER glucosidases I and II	672:695	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	9	theme	ER	672:673	arg1	II					694:695	II	694:695	II	694:695	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	9	theme	ER	672:673	arg1	I					688:688	I	688:688	I	688:688	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	5	10	theme	human	922:926	arg1	MANEA					928:932	human MANEA	922:932	human MANEA	922:932	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	3	11	theme	ER-escaped	580:589	arg1	glycoproteins					591:603	ER-escaped glycoproteins	580:603	ER-escaped glycoproteins	580:603	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	4	12	theme	N-linked	772:779	arg1	glycosylation					781:793	N-linked glycosylation	772:793	N-linked glycosylation	772:793	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	4	12	theme	N-linked	772:779	arg1	agents					810:815	therapeutic agents	798:815	therapeutic agents for diseases such as cancer and viral infection	798:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	4	13	theme	therapeutic	798:808	arg1	glycosylation					781:793	N-linked glycosylation	772:793	N-linked glycosylation	772:793	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	4	13	theme	therapeutic	798:808	arg1	agents					810:815	therapeutic agents	798:815	therapeutic agents for diseases such as cancer and viral infection	798:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	4	14	link	N-linked	772:779	arg1	glycosylation					781:793	N-linked glycosylation	772:793	N-linked glycosylation	772:793	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	4	14	link	N-linked	772:779	arg1	agents					810:815	therapeutic agents	798:815	therapeutic agents for diseases such as cancer and viral infection	798:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	4	15	theme	molecules	749:757	arg1	use					736:738	the use	732:738	the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection	732:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	7	16	from	infectivity	1338:1348	arg1	models					1406:1411	cellular models	1397:1411	cellular models	1397:1411	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	5	17	theme	complexes	938:946	arg1	MANEA					928:932	human MANEA	922:932	human MANEA	922:932	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	5	17	theme	complexes	938:946	arg1	complexes					938:946	complexes	938:946	complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding	938:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	5	17	theme	complexes	938:946	arg1	domain					912:917	the catalytic domain	898:917	the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding	898:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	7	18	theme	diarrhea	1366:1373	arg1	viruses					1386:1392	dengue viruses	1379:1392	dengue viruses in cellular models	1379:1411	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	7	18	theme	diarrhea	1366:1373	arg1	infectivity					1338:1348	the infectivity	1334:1348	the infectivity of bovine viral diarrhea	1334:1373	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	5	19	theme	loop	1018:1021	arg1	movements					1023:1031	dynamic loop movements	1010:1031	dynamic loop movements that occur on substrate binding	1010:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	5	20	theme	catalytic	902:910	arg1	MANEA					928:932	human MANEA	922:932	human MANEA	922:932	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	5	20	theme	catalytic	902:910	arg1	complexes					938:946	complexes	938:946	complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding	938:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	5	20	theme	catalytic	902:910	arg1	domain					912:917	the catalytic domain	898:917	the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding	898:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	6	21	theme	structural	1076:1085	arg1	features					1087:1094	structural features	1076:1094	structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis	1076:1192	We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis.
33154157	3	22	theme	sole	464:467	arg1	Endo-α-1,2-mannosidase					426:447	Endo-α-1,2-mannosidase	426:447	Endo-α-1,2-mannosidase (MANEA)	426:455	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	22	theme	sole	464:467	arg1	hydrolase					491:499	the sole endo-acting glycoside hydrolase	460:499	the sole endo-acting glycoside hydrolase involved in N-glycan trimming	460:529	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	7	23	theme	host	1273:1276	arg1	processing					1295:1304	host protein N-glycan processing	1273:1304	host protein N-glycan processing of viral glycans	1273:1321	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	5	24	with	complexes	938:946	arg1	inhibitors					971:980	substrate-derived inhibitors	953:980	substrate-derived inhibitors	953:980	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	7	25	theme	protein	1278:1284	arg1	processing					1295:1304	host protein N-glycan processing	1273:1304	host protein N-glycan processing of viral glycans	1273:1321	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	2	26	theme	endoplasmic	329:339	arg1	ER					352:353	ER	352:353	ER	352:353	N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases.
33154157	2	26	theme	endoplasmic	329:339	arg1	reticulum					341:349	the endoplasmic reticulum	325:349	the endoplasmic reticulum (ER)	325:354	N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases.
33154157	4	27	theme	considerable	707:718	arg1	interest					720:727	considerable interest	707:727	considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection	707:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	1	28	theme	Mammalian	91:99	arg1	glycosylation					118:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	8	29	theme	broad-spectrum	1474:1487	arg1	agents					1499:1504	broad-spectrum antiviral agents	1474:1504	broad-spectrum antiviral agents	1474:1504	These results may contribute to efforts aimed at developing broad-spectrum antiviral agents and help provide a more in-depth understanding of the biology of mammalian glycosylation.
33154157	2	30	theme	glycoside	379:387	arg1	hydrolases					389:398	glycoside hydrolases	379:398	glycoside hydrolases	379:398	N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases.
33154157	0	31	theme	endo-α-1,2-mannosidase	19:40	arg1	Structure					0:8	Structure	0:8	Structure of human endo-α-1,2-mannosidase (MANEA)	0:48	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	0	31	theme	endo-α-1,2-mannosidase	19:40	arg1	target					83:88	an antiviral host-glycosylation target	51:88	an antiviral host-glycosylation target	51:88	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	7	32	theme	cellular	1397:1404	arg1	models					1406:1411	cellular models	1397:1411	cellular models	1397:1411	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	7	33	theme	viral	1309:1313	arg1	glycans					1315:1321	viral glycans	1309:1321	viral glycans	1309:1321	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	1	34	theme	protein	101:107	arg1	glycosylation					118:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	7	35	theme	viral	1360:1364	arg1	diarrhea					1366:1373	bovine viral diarrhea	1353:1373	bovine viral diarrhea	1353:1373	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	0	36	theme	human	13:17	arg1	MANEA					43:47	MANEA	43:47	MANEA	43:47	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	0	36	theme	human	13:17	arg1	endo-α-1,2-mannosidase					19:40	human endo-α-1,2-mannosidase	13:40	human endo-α-1,2-mannosidase (MANEA)	13:48	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	1	37	gly	glycosylation	118:130	arg1	glycoprotein					148:159	glycoprotein folding	148:167	glycoprotein folding	148:167	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	1	37	gly	glycosylation	118:130	arg1	quality					170:176	quality control	170:184	quality control	170:184	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	1	38	theme	N-linked	109:116	arg1	glycosylation					118:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	5	39	theme	dynamic	1010:1016	arg1	movements					1023:1031	dynamic loop movements	1010:1031	dynamic loop movements that occur on substrate binding	1010:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	7	40	theme	bovine	1353:1358	arg1	diarrhea					1366:1373	bovine viral diarrhea	1353:1373	bovine viral diarrhea	1353:1373	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	7	41	theme	new	1245:1247	arg1	inhibitors					1249:1258	new inhibitors	1245:1258	new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models	1245:1411	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	3	42	theme	classical	619:627	arg1	pathway					654:660	the classical N-glycosylation trimming pathway	615:660	the classical N-glycosylation trimming pathway involving ER glucosidases I and II	615:695	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	5	43	theme	domain	912:917	arg1	structure					885:893	the structure	881:893	the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding	881:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	3	44	theme	endo-acting	469:479	arg1	Endo-α-1,2-mannosidase					426:447	Endo-α-1,2-mannosidase	426:447	Endo-α-1,2-mannosidase (MANEA)	426:455	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	44	theme	endo-acting	469:479	arg1	hydrolase					491:499	the sole endo-acting glycoside hydrolase	460:499	the sole endo-acting glycoside hydrolase involved in N-glycan trimming	460:529	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	6	45	theme	enzyme	1109:1114	arg1	features					1087:1094	structural features	1076:1094	structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis	1076:1192	We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis.
33154157	3	46	theme	N-glycosylation	629:643	arg1	pathway					654:660	the classical N-glycosylation trimming pathway	615:660	the classical N-glycosylation trimming pathway involving ER glucosidases I and II	615:695	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	47	theme	glycoside	481:489	arg1	Endo-α-1,2-mannosidase					426:447	Endo-α-1,2-mannosidase	426:447	Endo-α-1,2-mannosidase (MANEA)	426:455	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	47	theme	glycoside	481:489	arg1	hydrolase					491:499	the sole endo-acting glycoside hydrolase	460:499	the sole endo-acting glycoside hydrolase involved in N-glycan trimming	460:529	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	7	48	theme	inhibitors	1249:1258	arg1	development					1230:1240	the development	1226:1240	the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models	1226:1411	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	5	49	link	substrate-derived	953:969	arg1	inhibitors					971:980	substrate-derived inhibitors	953:980	substrate-derived inhibitors	953:980	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	7	50	theme	N-glycan	1286:1293	arg1	processing					1295:1304	host protein N-glycan processing	1273:1304	host protein N-glycan processing of viral glycans	1273:1321	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	2	51	theme	N-linked	227:234	arg1	glycans					236:242	N-linked glycans	227:242	N-linked glycans	227:242	N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases.
33154157	4	52	theme	small	743:747	arg1	molecules					749:757	small molecules	743:757	small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection	743:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	6	53	theme	human	1103:1107	arg1	enzyme					1109:1114	the human enzyme	1099:1114	the human enzyme	1099:1114	We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis.
33154157	1	54	gly	glycoprotein	148:159	arg1	glycoprotein					148:159	glycoprotein folding	148:167	glycoprotein folding	148:167	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	3	55	located	located	538:544	arg2	MANEA					450:454	MANEA	450:454	MANEA	450:454	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	55	located	located	538:544	arg1	Golgi					557:561	the Golgi	553:561	the Golgi	553:561	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	55	located	located	538:544	arg2	hydrolase					491:499	the sole endo-acting glycoside hydrolase	460:499	the sole endo-acting glycoside hydrolase involved in N-glycan trimming	460:529	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	55	located	located	538:544	arg2	Endo-α-1,2-mannosidase					426:447	Endo-α-1,2-mannosidase	426:447	Endo-α-1,2-mannosidase (MANEA)	426:455	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	56	gly	glycoproteins	591:603	arg1	glycoproteins					591:603	ER-escaped glycoproteins	580:603	ER-escaped glycoproteins	580:603	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	7	57	theme	glycans	1315:1321	arg1	processing					1295:1304	host protein N-glycan processing	1273:1304	host protein N-glycan processing of viral glycans	1273:1321	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	8	58	theme	in-depth	1530:1537	arg1	understanding					1539:1551	a more in-depth understanding	1523:1551	a more in-depth understanding of the biology of mammalian glycosylation	1523:1593	These results may contribute to efforts aimed at developing broad-spectrum antiviral agents and help provide a more in-depth understanding of the biology of mammalian glycosylation.
33154157	8	59	theme	antiviral	1489:1497	arg1	agents					1499:1504	broad-spectrum antiviral agents	1474:1504	broad-spectrum antiviral agents	1474:1504	These results may contribute to efforts aimed at developing broad-spectrum antiviral agents and help provide a more in-depth understanding of the biology of mammalian glycosylation.
33154157	4	60	theme	viral	849:853	arg1	infection					855:863	viral infection	849:863	viral infection	849:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	5	61	theme	substrate-derived	953:969	arg1	inhibitors					971:980	substrate-derived inhibitors	953:980	substrate-derived inhibitors	953:980	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	2	62	link	N-linked	227:234	arg1	glycans					236:242	N-linked glycans	227:242	N-linked glycans	227:242	N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases.
33154157	2	63	theme	Glc3Man9GlcNAc2	265:279	arg1	precursors					281:290	Glc3Man9GlcNAc2 precursors	265:290	Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases	265:423	N-linked glycans are synthesized from Glc3Man9GlcNAc2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases.
33154157	8	64	theme	biology	1560:1566	arg1	understanding					1539:1551	a more in-depth understanding	1523:1551	a more in-depth understanding of the biology of mammalian glycosylation	1523:1593	These results may contribute to efforts aimed at developing broad-spectrum antiviral agents and help provide a more in-depth understanding of the biology of mammalian glycosylation.
33154157	3	65	theme	N-glycan	513:520	arg1	trimming					522:529	N-glycan trimming	513:529	N-glycan trimming	513:529	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	6	66	theme	mechanistic	1162:1172	arg1	basis					1174:1178	the mechanistic basis	1158:1178	the mechanistic basis for catalysis	1158:1192	We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis.
33154157	0	67	theme	antiviral	54:62	arg1	Structure					0:8	Structure	0:8	Structure of human endo-α-1,2-mannosidase (MANEA)	0:48	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	0	67	theme	antiviral	54:62	arg1	target					83:88	an antiviral host-glycosylation target	51:88	an antiviral host-glycosylation target	51:88	Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.
33154157	4	68	from	interest	720:727	arg1	use					736:738	the use	732:738	the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection	732:863	There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection.
33154157	3	69	theme	trimming	645:652	arg1	pathway					654:660	the classical N-glycosylation trimming pathway	615:660	the classical N-glycosylation trimming pathway involving ER glucosidases I and II	615:695	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	1	70	theme	glycoprotein	148:159	arg1	folding					161:167	glycoprotein folding	148:167	glycoprotein folding	148:167	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	1	71	link	N-linked	109:116	arg1	glycosylation					118:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation	91:130	Mammalian protein N-linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition, and function.
33154157	5	72	theme	substrate	1047:1055	arg1	binding					1057:1063	substrate binding	1047:1063	substrate binding	1047:1063	Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur on substrate binding.
33154157	7	73	from	viruses	1386:1392	arg1	models					1406:1411	cellular models	1397:1411	cellular models	1397:1411	These structures have inspired the development of new inhibitors that disrupt host protein N-glycan processing of viral glycans and reduce the infectivity of bovine viral diarrhea and dengue viruses in cellular models.
33154157	3	74	dep	glucosidases	675:686	arg1	glucosidases					675:686	ER glucosidases I and II	672:695	ER glucosidases I and II	672:695	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	74	dep	glucosidases	675:686	arg1	II					694:695	II	694:695	II	694:695	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
33154157	3	74	dep	glucosidases	675:686	arg1	I					688:688	I	688:688	I	688:688	Endo-α-1,2-mannosidase (MANEA) is the sole endo-acting glycoside hydrolase involved in N-glycan trimming and is located within the Golgi, where it allows ER-escaped glycoproteins to bypass the classical N-glycosylation trimming pathway involving ER glucosidases I and II.
32553552	4	0	theme	Spodoptera	626:635	arg1	frugiperda					637:646	Spodoptera frugiperda	626:646	Spodoptera frugiperda	626:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	6	1	theme	N-glycans	900:908	arg1	compositions					875:886	the compositions	871:886	the compositions of released N-glycans	871:908	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	8	2	theme	observed	1258:1265	arg1	glycans					1267:1273	the observed glycans	1254:1273	the observed glycans	1254:1273	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	6	3	theme	sites	998:1002	arg1	occupancy					955:963	the occupancy	951:963	the occupancy of the potential N-glycosylation sites	951:1002	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	7	4	gly	glycopeptides	1035:1047	arg2	glycopeptides					1035:1047	160 glycopeptides	1031:1047	160 glycopeptides	1031:1047	We report here a total of 160 glycopeptides, representing 25 N-glycan compositions associated with 70 sites on 35 glycoproteins.
32553552	2	5	theme	different	303:311	arg1	organisms					313:321	different organisms	303:321	different organisms as well as plant lectins	303:346	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	6	6	theme	potential	972:980	arg1	sites					998:1002	the potential N-glycosylation sites	968:1002	the potential N-glycosylation sites	968:1002	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	5	7	theme	proteolytic	697:707	arg1	digestion					709:717	proteolytic digestion	697:717	proteolytic digestion	697:717	We subjected midgut cell microvilli proteins to proteolytic digestion and enriched the resulting glycopeptides prior to analysis.
32553552	9	8	theme	N-glycan	1310:1317	arg1	Hex3HexNAc4dHex4					1356:1371	the complex/hybrid Hex3HexNAc4dHex4	1337:1371	the complex/hybrid Hex3HexNAc4dHex4	1337:1371	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	9	8	theme	N-glycan	1310:1317	arg1	compositions					1319:1330	The two most common N-glycan compositions	1290:1330	The two most common N-glycan compositions	1290:1330	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	8	9	with	consistent	1154:1163	arg1	paucimannose					1184:1195	paucimannose	1184:1195	paucimannose	1184:1195	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	8	9	with	consistent	1154:1163	arg1	N-glycans					1216:1224	complex/hybrid N-glycans	1201:1224	complex/hybrid N-glycans	1201:1224	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	8	9	with	consistent	1154:1163	arg1	oligomannose					1170:1181	oligomannose	1170:1181	oligomannose	1170:1181	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	9	10	theme	complex/hybrid	1341:1354	arg1	Hex3HexNAc4dHex4					1356:1371	the complex/hybrid Hex3HexNAc4dHex4	1337:1371	the complex/hybrid Hex3HexNAc4dHex4	1337:1371	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	9	10	theme	complex/hybrid	1341:1354	arg1	compositions					1319:1330	The two most common N-glycan compositions	1290:1330	The two most common N-glycan compositions	1290:1330	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	2	11	theme	microvillar	236:246	arg1	membrane					248:255	the midgut microvillar membrane	225:255	the midgut microvillar membrane of insects	225:266	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	6	12	gly	N-glycosylation	982:996	arg2	sites					998:1002	the potential N-glycosylation sites	968:1002	the potential N-glycosylation sites	968:1002	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	9	13	theme	paucimannose	1381:1392	arg1	each					1491:1494	each	1491:1494	each	1491:1494	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	9	13	theme	paucimannose	1381:1392	arg1	structure					1394:1402	the paucimannose structure	1377:1402	the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1377:1488	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	1	14	theme	agricultural	149:160	arg1	frugiperda					114:123	Spodoptera frugiperda	103:123	Spodoptera frugiperda	103:123	Spodoptera frugiperda is a widely distributed agricultural pest.
32553552	1	14	theme	agricultural	149:160	arg1	pest					162:165	a widely distributed agricultural pest	128:165	a widely distributed agricultural pest	128:165	Spodoptera frugiperda is a widely distributed agricultural pest.
32553552	5	15	gly	glycopeptides	746:758	arg2	glycopeptides					746:758	the resulting glycopeptides	732:758	the resulting glycopeptides prior to analysis	732:776	We subjected midgut cell microvilli proteins to proteolytic digestion and enriched the resulting glycopeptides prior to analysis.
32553552	7	16	theme	25 N-glycan	1063:1073	arg1	compositions					1075:1086	25 N-glycan compositions	1063:1086	25 N-glycan compositions associated with 70 sites on 35 glycoproteins	1063:1131	We report here a total of 160 glycopeptides, representing 25 N-glycan compositions associated with 70 sites on 35 glycoproteins.
32553552	4	17	theme	spectrometry-based	519:536	arg1	approaches					538:547	mass spectrometry-based approaches	514:547	mass spectrometry-based approaches	514:547	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	0	18	theme	membrane-bound	73:86	arg1	glycoproteins					88:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	0	19	from	N-glycosylation	0:14	arg1	glycoproteins					88:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	9	20	theme	doubly-fucosylated	1427:1444	arg1	Hex3HexNAc2dHex2					1473:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	8	21	theme	Glycan	1134:1139	arg1	compositions					1141:1152	Glycan compositions	1134:1152	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans	1134:1224	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	5	22	theme	midgut	662:667	arg1	proteins					685:692	midgut cell microvilli proteins	662:692	midgut cell microvilli proteins	662:692	We subjected midgut cell microvilli proteins to proteolytic digestion and enriched the resulting glycopeptides prior to analysis.
32553552	4	23	theme	present	495:501	arg1	study					503:507	The present study	491:507	The present study	491:507	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	9	24	theme	core	1468:1471	arg1	Hex3HexNAc2dHex2					1473:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	8	25	theme	consistent	1154:1163	arg1	compositions					1141:1152	Glycan compositions	1134:1152	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans	1134:1224	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	0	26	gly	glycoproteins	88:100	arg1	glycoproteins					88:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	10	27	theme	midgut	1605:1610	arg1	microvilli					1612:1621	lepidopteran midgut microvilli	1592:1621	lepidopteran midgut microvilli	1592:1621	These findings enlighten aspects of the glycobiology of lepidopteran midgut microvilli.
32553552	1	28	theme	Spodoptera	103:112	arg1	frugiperda					114:123	Spodoptera frugiperda	103:123	Spodoptera frugiperda	103:123	Spodoptera frugiperda is a widely distributed agricultural pest.
32553552	1	28	theme	Spodoptera	103:112	arg1	pest					162:165	a widely distributed agricultural pest	128:165	a widely distributed agricultural pest	128:165	Spodoptera frugiperda is a widely distributed agricultural pest.
32553552	6	29	gly	occupancy	955:963	arg2	sites					998:1002	the potential N-glycosylation sites	968:1002	the potential N-glycosylation sites	968:1002	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	0	30	theme	Spodoptera	19:28	arg1	frugiperda					30:39	Spodoptera frugiperda	19:39	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	3	31	theme	midgut	430:435	arg1	glycoproteins					437:449	membrane-bound midgut glycoproteins	415:449	membrane-bound midgut glycoproteins in Lepidoptera and other insect groups	415:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	4	32	theme	cell	607:610	arg1	microvilli					612:621	the midgut cell microvilli	596:621	the midgut cell microvilli of Spodoptera frugiperda	596:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	3	33	theme	insect	476:481	arg1	groups					483:488	other insect groups	470:488	other insect groups	470:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	4	34	from	present	585:591	arg1	microvilli					612:621	the midgut cell microvilli	596:621	the midgut cell microvilli of Spodoptera frugiperda	596:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	8	35	theme	complex/hybrid	1201:1214	arg1	N-glycans					1216:1224	complex/hybrid N-glycans	1201:1224	complex/hybrid N-glycans	1201:1224	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	3	36	from	groups	483:488	arg1	N-glycome					402:410	the N-glycome	398:410	the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups	398:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	4	37	theme	present	585:591	arg1	N-glycoproteins					569:583	the N-glycoproteins	565:583	the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda	565:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	6	38	theme	N-glycans	824:832	arg1	release					813:819	endoglycosidase release	797:819	endoglycosidase release of N-glycans	797:832	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	6	39	theme	MALDI-TOF	913:921	arg1	analysis					926:933	MALDI-TOF MS analysis	913:933	MALDI-TOF MS analysis	913:933	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	3	40	from	Lepidoptera	454:464	arg1	N-glycome					402:410	the N-glycome	398:410	the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups	398:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	6	41	theme	released	891:898	arg1	N-glycans					900:908	released N-glycans	891:908	released N-glycans	891:908	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	2	42	from	glycoproteins	208:220	arg1	membrane					248:255	the midgut microvillar membrane	225:255	the midgut microvillar membrane of insects	225:266	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	6	43	theme	N-glycosylation	982:996	arg1	sites					998:1002	the potential N-glycosylation sites	968:1002	the potential N-glycosylation sites	968:1002	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	6	44	dep	H218O	853:857	arg1	the					837:839	the	837:839	the	837:839	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	6	44	dep	H218O	853:857	arg1	presence					841:848	presence	841:848	presence	841:848	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	4	45	theme	frugiperda	637:646	arg1	microvilli					612:621	the midgut cell microvilli	596:621	the midgut cell microvilli of Spodoptera frugiperda	596:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	5	46	theme	microvilli	674:683	arg1	proteins					685:692	midgut cell microvilli proteins	662:692	midgut cell microvilli proteins	662:692	We subjected midgut cell microvilli proteins to proteolytic digestion and enriched the resulting glycopeptides prior to analysis.
32553552	8	47	theme	glycans	1267:1273	arg1	%					1249:1249	35, 30 and 35%	1236:1249	35, 30 and 35% of the observed glycans	1236:1273	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	8	47	theme	glycans	1267:1273	arg1	glycans					1267:1273	the observed glycans	1254:1273	the observed glycans	1254:1273	Glycan compositions consistent with oligomannose, paucimannose and complex/hybrid N-glycans represent 35, 30 and 35% of the observed glycans, respectively.
32553552	9	48	theme	common	1303:1308	arg1	Hex3HexNAc4dHex4					1356:1371	the complex/hybrid Hex3HexNAc4dHex4	1337:1371	the complex/hybrid Hex3HexNAc4dHex4	1337:1371	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	9	48	theme	common	1303:1308	arg1	compositions					1319:1330	The two most common N-glycan compositions	1290:1330	The two most common N-glycan compositions	1290:1330	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	2	49	theme	plant	334:338	arg1	lectins					340:346	plant lectins	334:346	different organisms as well as plant lectins	303:346	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	4	50	attach	present	585:591	arg2	N-glycoproteins					569:583	the N-glycoproteins	565:583	the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda	565:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	4	50	attach	present	585:591	arg1	microvilli					612:621	the midgut cell microvilli	596:621	the midgut cell microvilli of Spodoptera frugiperda	596:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	7	51	from	sites	1107:1111	arg1	glycoproteins					1119:1131	35 glycoproteins	1116:1131	35 glycoproteins	1116:1131	We report here a total of 160 glycopeptides, representing 25 N-glycan compositions associated with 70 sites on 35 glycoproteins.
32553552	2	52	theme	insects	260:266	arg1	membrane					248:255	the midgut microvillar membrane	225:255	the midgut microvillar membrane of insects	225:266	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	5	53	theme	resulting	736:744	arg1	glycopeptides					746:758	the resulting glycopeptides	732:758	the resulting glycopeptides prior to analysis	732:776	We subjected midgut cell microvilli proteins to proteolytic digestion and enriched the resulting glycopeptides prior to analysis.
32553552	1	54	theme	distributed	137:147	arg1	frugiperda					114:123	Spodoptera frugiperda	103:123	Spodoptera frugiperda	103:123	Spodoptera frugiperda is a widely distributed agricultural pest.
32553552	1	54	theme	distributed	137:147	arg1	pest					162:165	a widely distributed agricultural pest	128:165	a widely distributed agricultural pest	128:165	Spodoptera frugiperda is a widely distributed agricultural pest.
32553552	7	55	gly	glycoproteins	1119:1131	arg1	glycoproteins					1119:1131	35 glycoproteins	1116:1131	35 glycoproteins	1116:1131	We report here a total of 160 glycopeptides, representing 25 N-glycan compositions associated with 70 sites on 35 glycoproteins.
32553552	2	56	gly	glycoproteins	208:220	arg1	targets					272:278	targets	272:278	targets for toxins produced by different organisms as well as plant lectins	272:346	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	2	56	gly	glycoproteins	208:220	arg1	glycoproteins					208:220	glycoproteins	208:220	glycoproteins in the midgut microvillar membrane of insects	208:266	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	0	57	theme	midgut	66:71	arg1	glycoproteins					88:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	4	58	gly	N-glycoproteins	569:583	arg1	N-glycoproteins					569:583	the N-glycoproteins	565:583	the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda	565:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	9	59	gly	doubly-fucosylated	1427:1444	arg1	Hex3HexNAc2dHex2					1473:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	3	60	gly	glycoproteins	437:449	arg1	glycoproteins					437:449	membrane-bound midgut glycoproteins	415:449	membrane-bound midgut glycoproteins in Lepidoptera and other insect groups	415:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	10	61	theme	glycobiology	1576:1587	arg1	aspects					1561:1567	aspects	1561:1567	aspects of the glycobiology of lepidopteran midgut microvilli	1561:1621	These findings enlighten aspects of the glycobiology of lepidopteran midgut microvilli.
32553552	3	62	from	glycoproteins	437:449	arg1	groups					483:488	other insect groups	470:488	other insect groups	470:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	3	62	from	glycoproteins	437:449	arg1	Lepidoptera					454:464	Lepidoptera	454:464	Lepidoptera	454:464	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	3	63	theme	little	373:378	arg1	information					380:390	little information	373:390	little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups	373:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	9	64	theme	trimannosylchitobiose	1446:1466	arg1	Hex3HexNAc2dHex2					1473:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	5	65	theme	cell	669:672	arg1	proteins					685:692	midgut cell microvilli proteins	662:692	midgut cell microvilli proteins	662:692	We subjected midgut cell microvilli proteins to proteolytic digestion and enriched the resulting glycopeptides prior to analysis.
32553552	4	66	theme	mass	514:517	arg1	approaches					538:547	mass spectrometry-based approaches	514:547	mass spectrometry-based approaches	514:547	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	10	67	theme	microvilli	1612:1621	arg1	glycobiology					1576:1587	the glycobiology	1572:1587	the glycobiology of lepidopteran midgut microvilli	1572:1621	These findings enlighten aspects of the glycobiology of lepidopteran midgut microvilli.
32553552	9	68	contain	contains	1409:1416	arg2	Hex3HexNAc2dHex2					1473:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1418:1488	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	9	68	contain	contains	1409:1416	arg1	each					1491:1494	each	1491:1494	each	1491:1494	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	9	68	contain	contains	1409:1416	arg1	structure					1394:1402	the paucimannose structure	1377:1402	the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2	1377:1488	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	3	69	theme	other	470:474	arg1	groups					483:488	other insect groups	470:488	other insect groups	470:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	4	70	from	microvilli	612:621	arg1	present					585:591	present	585:591	present	585:591	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	3	71	from	N-glycome	402:410	arg1	groups					483:488	other insect groups	470:488	other insect groups	470:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	3	71	from	N-glycome	402:410	arg1	Lepidoptera					454:464	Lepidoptera	454:464	Lepidoptera	454:464	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	4	72	theme	midgut	600:605	arg1	microvilli					612:621	the midgut cell microvilli	596:621	the midgut cell microvilli of Spodoptera frugiperda	596:646	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	10	73	theme	lepidopteran	1592:1603	arg1	microvilli					1612:1621	lepidopteran midgut microvilli	1592:1621	lepidopteran midgut microvilli	1592:1621	These findings enlighten aspects of the glycobiology of lepidopteran midgut microvilli.
32553552	0	74	theme	frugiperda	30:39	arg1	glycoproteins					88:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	7	75	theme	glycopeptides	1035:1047	arg1	total					1022:1026	a total	1020:1026	a total of 160 glycopeptides	1020:1047	We report here a total of 160 glycopeptides, representing 25 N-glycan compositions associated with 70 sites on 35 glycoproteins.
32553552	4	76	used	used	509:512	arg2	study					503:507	The present study	491:507	The present study	491:507	The present study used mass spectrometry-based approaches to characterize the N-glycoproteins present in the midgut cell microvilli of Spodoptera frugiperda.
32553552	0	77	gly	N-glycosylation	0:14	arg1	glycoproteins					88:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins	19:100	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	3	78	theme	glycoproteins	437:449	arg1	N-glycome					402:410	the N-glycome	398:410	the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups	398:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	9	79	theme	occupied	1512:1519	arg1	sites					1521:1525	22 occupied sites	1509:1525	22 occupied sites (13.8%)	1509:1533	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	9	79	theme	occupied	1512:1519	arg1	%					1532:1532	13.8%	1528:1532	13.8%	1528:1532	The two most common N-glycan compositions were the complex/hybrid Hex3HexNAc4dHex4 and the paucimannose structure that contains only the doubly-fucosylated trimannosylchitobiose core Hex3HexNAc2dHex2, each appearing in 22 occupied sites (13.8%).
32553552	0	80	dep	Lepidoptera	42:52	arg1	Noctuidae					55:63	Noctuidae	55:63	Noctuidae	55:63	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	3	81	theme	membrane-bound	415:428	arg1	glycoproteins					437:449	membrane-bound midgut glycoproteins	415:449	membrane-bound midgut glycoproteins in Lepidoptera and other insect groups	415:488	However, there is still little information about the N-glycome of membrane-bound midgut glycoproteins in Lepidoptera and other insect groups.
32553552	2	82	theme	midgut	229:234	arg1	membrane					248:255	the midgut microvillar membrane	225:255	the midgut microvillar membrane of insects	225:266	It has previously been established that glycoproteins in the midgut microvillar membrane of insects are targets for toxins produced by different organisms as well as plant lectins.
32553552	6	83	theme	MS	923:924	arg1	analysis					926:933	MALDI-TOF MS analysis	913:933	MALDI-TOF MS analysis	913:933	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32553552	0	84	dep	frugiperda	30:39	arg1	Lepidoptera					42:52	Lepidoptera	42:52	Lepidoptera	42:52	N-glycosylation in Spodoptera frugiperda (Lepidoptera: Noctuidae) midgut membrane-bound glycoproteins.
32553552	6	85	theme	endoglycosidase	797:811	arg1	release					813:819	endoglycosidase release	797:819	endoglycosidase release of N-glycans	797:832	We also performed endoglycosidase release of N-glycans in the presence of H218O determining the compositions of released N-glycans by MALDI-TOF MS analysis and established the occupancy of the potential N-glycosylation sites.
32693290	5	0	theme	near	951:954	arg1	Dichroism					968:976	near UV Circular Dichroism	951:976	near UV Circular Dichroism studies	951:984	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	3	1	theme	activation	649:658	arg1	peptide					660:666	the activation peptide	645:666	the activation peptide (Thr159, Thr163 and Thr169)	645:694	Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously.
32693290	1	2	theme	recombinant	155:165	arg1	rFIX					178:181	rFIX	178:181	rFIX	178:181	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	1	2	theme	recombinant	155:165	arg1	IX					174:175	recombinant factor IX	155:175	recombinant factor IX (rFIX)	155:182	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	1	3	theme	order	224:228	arg1	structure					230:238	the primary and higher order structure	201:238	the primary and higher order structure of activated factor IX	201:261	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	6	4	dep	1 °C	1159:1162	arg1	higher					1164:1169	higher	1164:1169	higher	1164:1169	The thermally induced unfolding of rFIX and N9-GP shows that the unfolding temperature is approximately 1 °C higher for N9-GP than that of the rFIX.
32693290	4	5	dep	ratio	902:906	arg1	to					895:896	to	895:896	to	895:896	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	1	6	theme	factor	167:172	arg1	rFIX					178:181	rFIX	178:181	rFIX	178:181	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	1	6	theme	factor	167:172	arg1	IX					174:175	recombinant factor IX	155:175	recombinant factor IX (rFIX)	155:182	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	8	7	dep	pegol	1378:1382	arg1	Rebinyn®					1385:1392	Rebinyn®	1385:1392	Rebinyn®	1385:1392	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	8	8	theme	Refixia®	1355:1362	arg1	manufacturing					1338:1350	the manufacturing	1334:1350	the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark)	1334:1431	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	5	9	theme	rFIX	1039:1042	arg1	structures					1025:1034	comparable secondary and tertiary structures	991:1034	comparable secondary and tertiary structures of rFIX and N9-GP	991:1052	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	2	10	theme	glycan	543:548	arg1	structures					550:559	N-linked glycan structures	534:559	N-linked glycan structures	534:559	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	4	11	from	peptide	878:884	arg1	ratio					902:906	a one to one ratio	889:906	a one to one ratio	889:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	4	11	from	peptide	878:884	arg1	present					831:837	present	831:837	present	831:837	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	2	12	theme	Characterisation	264:279	arg1	work					281:284	Characterisation work	264:284	Characterisation work	264:284	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	7	13	theme	rFIX	1288:1291	arg1	GlycoPEGylation					1269:1283	the GlycoPEGylation	1265:1283	the GlycoPEGylation of rFIX	1265:1291	Furthermore, the pH dependent degradation was reduced due to the GlycoPEGylation of rFIX.
32693290	4	14	link	N-linked	814:821	arg1	glycans					823:829	the two N-linked glycans	806:829	the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio	806:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	2	15	theme	N-linked	534:541	arg1	structures					550:559	N-linked glycan structures	534:559	N-linked glycan structures	534:559	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	16	theme	GlycoPEGylated	332:345	arg1	form					347:350	the GlycoPEGylated form	328:350	the GlycoPEGylated form of rFIX (N9-GP)	328:366	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	4	17	attach	present	831:837	arg1	Asn157					842:847	Asn157	842:847	Asn157	842:847	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	4	17	attach	present	831:837	arg1	Asn167					853:858	Asn167	853:858	Asn167	853:858	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	4	17	attach	present	831:837	arg2	glycans					823:829	the two N-linked glycans	806:829	the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio	806:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	4	17	attach	present	831:837	arg1	peptide					878:884	the activation peptide	863:884	the activation peptide in a one to one ratio	863:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	1	18	theme	activated	243:251	arg1	IX					260:261	activated factor IX	243:261	activated factor IX	243:261	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	2	19	theme	disulphide	460:469	arg1	bonds					471:475	disulphide bonds	460:475	disulphide bonds	460:475	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	5	20	theme	comparable	991:1000	arg1	structures					1025:1034	comparable secondary and tertiary structures	991:1034	comparable secondary and tertiary structures of rFIX and N9-GP	991:1052	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	4	21	theme	mono	759:762	arg1	GlycoPEGylation					764:778	the mono GlycoPEGylation	755:778	the mono GlycoPEGylation	755:778	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	6	22	theme	induced	1069:1075	arg1	unfolding					1077:1085	The thermally induced unfolding	1055:1085	The thermally induced unfolding of rFIX and N9-GP	1055:1103	The thermally induced unfolding of rFIX and N9-GP shows that the unfolding temperature is approximately 1 °C higher for N9-GP than that of the rFIX.
32693290	1	23	theme	IX	174:175	arg1	half-life					142:150	the half-life	138:150	the half-life of recombinant factor IX (rFIX)	138:182	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	4	24	from	Asn167	853:858	arg1	present					831:837	present	831:837	present	831:837	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	5	25	theme	secondary	1002:1010	arg1	structures					1025:1034	comparable secondary and tertiary structures	991:1034	comparable secondary and tertiary structures of rFIX and N9-GP	991:1052	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	4	26	theme	activation	867:876	arg1	peptide					878:884	the activation peptide	863:884	the activation peptide in a one to one ratio	863:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	2	27	theme	recombinant	299:309	arg1	IX					318:319	recombinant factor IX	299:319	recombinant factor IX	299:319	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	1	28	theme	factor	253:258	arg1	IX					260:261	activated factor IX	243:261	activated factor IX	243:261	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	3	29	theme	glycan	613:618	arg1	sites					620:624	Three O-linked glycan sites	598:624	Three O-linked glycan sites	598:624	Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously.
32693290	2	30	theme	rFIX	355:358	arg1	form					347:350	the GlycoPEGylated form	328:350	the GlycoPEGylated form of rFIX (N9-GP)	328:366	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	0	31	theme	factor	32:37	arg1	IX					39:40	recombinant factor IX	20:40	recombinant factor IX	20:40	Characterisation of recombinant factor IX before and after GlycoPEGylation.
32693290	1	32	theme	IX	260:261	arg1	structure					230:238	the primary and higher order structure	201:238	the primary and higher order structure of activated factor IX	201:261	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	1	33	theme	GlycoPEGylation	94:108	arg1	process					110:116	the GlycoPEGylation process	90:116	the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX)	90:182	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	8	34	theme	beta	1373:1376	arg1	pegol					1378:1382	nonacog beta pegol	1365:1382	nonacog beta pegol	1365:1382	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	2	35	theme	primary	386:392	arg1	comparable					567:576	comparable	567:576	comparable	567:576	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	35	theme	primary	386:392	arg1	structure					394:402	the primary structure	382:402	the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures)	382:560	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	4	36	theme	present	831:837	arg1	glycans					823:829	the two N-linked glycans	806:829	the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio	806:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	5	37	theme	UV	956:957	arg1	Dichroism					968:976	near UV Circular Dichroism	951:976	near UV Circular Dichroism studies	951:984	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	1	38	theme	process	110:116	arg1	effect					80:85	The effect	76:85	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX)	76:182	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	2	39	theme	translational	424:436	arg1	sulphation					512:521	sulphation	512:521	sulphation	512:521	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	39	theme	translational	424:436	arg1	modifications					438:450	the post translational modifications	415:450	the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures)	382:560	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	39	theme	translational	424:436	arg1	O-					527:528	O-	527:528	O-	527:528	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	39	theme	translational	424:436	arg1	PTMs					453:456	PTMs	453:456	PTMs	453:456	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	39	theme	translational	424:436	arg1	comparable					567:576	comparable	567:576	comparable	567:576	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	39	theme	translational	424:436	arg1	γ-carboxylation					478:492	γ-carboxylation	478:492	γ-carboxylation	478:492	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	39	theme	translational	424:436	arg1	β-hydroxylation					495:509	β-hydroxylation	495:509	β-hydroxylation	495:509	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	8	40	used	used	1325:1328	arg2	N9-GP					1315:1319	N9-GP	1315:1319	N9-GP	1315:1319	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	8	40	used	used	1325:1328	arg2	rFIX					1309:1312	GlycoPEGylated rFIX	1294:1312	GlycoPEGylated rFIX (N9-GP)	1294:1320	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	4	41	from	Asn157	842:847	arg1	present					831:837	present	831:837	present	831:837	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	5	42	theme	Spectroscopic	909:921	arg1	techniques					923:932	Spectroscopic techniques	909:932	Spectroscopic techniques	909:932	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	5	42	theme	Spectroscopic	909:921	arg1	far					943:945	far	943:945	far	943:945	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	0	43	theme	IX	39:40	arg1	Characterisation					0:15	Characterisation	0:15	Characterisation of recombinant factor IX before and after GlycoPEGylation	0:73	Characterisation of recombinant factor IX before and after GlycoPEGylation.
32693290	3	44	dep	peptide	660:666	arg1	Thr169					688:693	Thr169	688:693	Thr169	688:693	Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously.
32693290	3	44	dep	peptide	660:666	arg1	Thr163					677:682	Thr163	677:682	Thr163	677:682	Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously.
32693290	3	44	dep	peptide	660:666	arg1	Thr159					669:674	Thr159	669:674	Thr159	669:674	Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously.
32693290	2	45	theme	post	419:422	arg1	sulphation					512:521	sulphation	512:521	sulphation	512:521	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	45	theme	post	419:422	arg1	modifications					438:450	the post translational modifications	415:450	the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures)	382:560	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	45	theme	post	419:422	arg1	O-					527:528	O-	527:528	O-	527:528	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	45	theme	post	419:422	arg1	PTMs					453:456	PTMs	453:456	PTMs	453:456	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	45	theme	post	419:422	arg1	comparable					567:576	comparable	567:576	comparable	567:576	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	45	theme	post	419:422	arg1	γ-carboxylation					478:492	γ-carboxylation	478:492	γ-carboxylation	478:492	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	45	theme	post	419:422	arg1	β-hydroxylation					495:509	β-hydroxylation	495:509	β-hydroxylation	495:509	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	5	46	theme	Dichroism	968:976	arg1	far					943:945	far	943:945	far	943:945	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	5	46	theme	Dichroism	968:976	arg1	studies					978:984	near UV Circular Dichroism studies	951:984	near UV Circular Dichroism studies	951:984	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	6	47	theme	unfolding	1120:1128	arg1	1 °C					1159:1162	1 °C	1159:1162	1 °C	1159:1162	The thermally induced unfolding of rFIX and N9-GP shows that the unfolding temperature is approximately 1 °C higher for N9-GP than that of the rFIX.
32693290	6	47	theme	unfolding	1120:1128	arg1	temperature					1130:1140	the unfolding temperature	1116:1140	the unfolding temperature	1116:1140	The thermally induced unfolding of rFIX and N9-GP shows that the unfolding temperature is approximately 1 °C higher for N9-GP than that of the rFIX.
32693290	8	48	dep	Rebinyn®	1385:1392	arg1	Bagsvaerd					1413:1421	Bagsvaerd	1413:1421	Bagsvaerd	1413:1421	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	8	48	dep	Rebinyn®	1385:1392	arg1	Denmark					1424:1430	Denmark	1424:1430	Denmark	1424:1430	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	5	49	theme	N9-GP	1048:1052	arg1	structures					1025:1034	comparable secondary and tertiary structures	991:1034	comparable secondary and tertiary structures of rFIX and N9-GP	991:1052	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	4	50	from	present	831:837	arg1	peptide					878:884	the activation peptide	863:884	the activation peptide in a one to one ratio	863:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	8	51	theme	nonacog	1365:1371	arg1	pegol					1378:1382	nonacog beta pegol	1365:1382	nonacog beta pegol	1365:1382	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	8	52	theme	GlycoPEGylated	1294:1307	arg1	N9-GP					1315:1319	N9-GP	1315:1319	N9-GP	1315:1319	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	8	52	theme	GlycoPEGylated	1294:1307	arg1	rFIX					1309:1312	GlycoPEGylated rFIX	1294:1312	GlycoPEGylated rFIX (N9-GP)	1294:1320	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	2	53	dep	modifications	438:450	arg1	structures					550:559	N-linked glycan structures	534:559	N-linked glycan structures	534:559	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	53	dep	modifications	438:450	arg1	γ-carboxylation					478:492	γ-carboxylation	478:492	γ-carboxylation	478:492	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	53	dep	modifications	438:450	arg1	bonds					471:475	disulphide bonds	460:475	disulphide bonds	460:475	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	2	53	dep	modifications	438:450	arg1	modifications					438:450	the post translational modifications	415:450	the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures)	382:560	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	3	54	link	O-linked	604:611	arg1	sites					620:624	Three O-linked glycan sites	598:624	Three O-linked glycan sites	598:624	Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously.
32693290	6	55	theme	rFIX	1090:1093	arg1	unfolding					1077:1085	The thermally induced unfolding	1055:1085	The thermally induced unfolding of rFIX and N9-GP	1055:1103	The thermally induced unfolding of rFIX and N9-GP shows that the unfolding temperature is approximately 1 °C higher for N9-GP than that of the rFIX.
32693290	4	56	theme	glycans	823:829	arg1	glycans					823:829	the two N-linked glycans	806:829	the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio	806:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	4	56	theme	glycans	823:829	arg1	one					799:801	one	799:801	one	799:801	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	2	57	link	N-linked	534:541	arg1	structures					550:559	N-linked glycan structures	534:559	N-linked glycan structures	534:559	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	4	58	theme	N-linked	814:821	arg1	glycans					823:829	the two N-linked glycans	806:829	the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio	806:906	For N9-GP, the mono GlycoPEGylation is directed toward one of the two N-linked glycans present at Asn157 and Asn167 in the activation peptide in a one to one ratio.
32693290	3	59	theme	O-linked	604:611	arg1	sites					620:624	Three O-linked glycan sites	598:624	Three O-linked glycan sites	598:624	Three O-linked glycan sites were identified in the activation peptide (Thr159, Thr163 and Thr169), where Thr163 has not been reported previously.
32693290	6	60	theme	N9-GP	1099:1103	arg1	unfolding					1077:1085	The thermally induced unfolding	1055:1085	The thermally induced unfolding of rFIX and N9-GP	1055:1103	The thermally induced unfolding of rFIX and N9-GP shows that the unfolding temperature is approximately 1 °C higher for N9-GP than that of the rFIX.
32693290	5	61	theme	Circular	959:966	arg1	Dichroism					968:976	near UV Circular Dichroism	951:976	near UV Circular Dichroism studies	951:984	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	2	62	theme	factor	311:316	arg1	IX					318:319	recombinant factor IX	299:319	recombinant factor IX	299:319	Characterisation work performed on recombinant factor IX and on the GlycoPEGylated form of rFIX (N9-GP), confirm that the primary structure as well as the post translational modifications (PTMs) (disulphide bonds, γ-carboxylation, β-hydroxylation, sulphation and O- and N-linked glycan structures) were comparable for rFIX and N9-GP.
32693290	1	63	theme	primary	205:211	arg1	structure					230:238	the primary and higher order structure	201:238	the primary and higher order structure of activated factor IX	201:261	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	8	64	dep	Refixia®	1355:1362	arg1	pegol					1378:1382	nonacog beta pegol	1365:1382	nonacog beta pegol	1365:1382	GlycoPEGylated rFIX (N9-GP) is used for the manufacturing of Refixia® (nonacog beta pegol, Rebinyn®, Novo Nordisk A/S, Bagsvaerd, Denmark).
32693290	1	65	contain	has	184:186	arg2	impact					191:196	no impact	188:196	no impact	188:196	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	1	65	contain	has	184:186	arg1	effect					80:85	The effect	76:85	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX)	76:182	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32693290	7	66	theme	dependent	1224:1232	arg1	degradation					1234:1244	the pH dependent degradation	1217:1244	the pH dependent degradation	1217:1244	Furthermore, the pH dependent degradation was reduced due to the GlycoPEGylation of rFIX.
32693290	5	67	theme	tertiary	1016:1023	arg1	structures					1025:1034	comparable secondary and tertiary structures	991:1034	comparable secondary and tertiary structures of rFIX and N9-GP	991:1052	Spectroscopic techniques, such as far and near UV Circular Dichroism studies show comparable secondary and tertiary structures of rFIX and N9-GP.
32693290	0	68	theme	recombinant	20:30	arg1	IX					39:40	recombinant factor IX	20:40	recombinant factor IX	20:40	Characterisation of recombinant factor IX before and after GlycoPEGylation.
32693290	1	69	theme	higher	217:222	arg1	structure					230:238	the primary and higher order structure	201:238	the primary and higher order structure of activated factor IX	201:261	The effect of the GlycoPEGylation process used for prolonging the half-life of recombinant factor IX (rFIX) has no impact on the primary and higher order structure of activated factor IX.
32080177	5	0	theme	α-helix	752:758	arg1	series					729:734	a series	727:734	a series of loops and an α-helix which all contribute in forming the binding site	727:807	FUT8 follows an SN2 mechanism and deploys a series of loops and an α-helix which all contribute in forming the binding site.
32080177	1	1	link	N-linked	244:251	arg1	glycans					253:259	N-linked glycans	244:259	N-linked glycans	244:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	6	2	theme	loops	845:849	arg1	one					832:834	one	832:834	one	832:834	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	6	2	theme	loops	845:849	arg1	loops					845:849	these loops	839:849	these loops	839:849	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	6	2	theme	loops	845:849	arg1	domain					862:867	an SH3 domain	855:867	an SH3 domain	855:867	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	4	3	theme	complex	592:598	arg1	N-glycan					600:607	a biantennary complex N-glycan	578:607	a biantennary complex N-glycan (G0)	578:612	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	4	3	theme	complex	592:598	arg1	G0					610:611	G0	610:611	G0	610:611	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	4	4	theme	crystal	529:535	arg1	structure					537:545	the crystal structure	525:545	the crystal structure of FUT8 complexed with GDP	525:572	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	4	5	theme	biantennary	580:590	arg1	N-glycan					600:607	a biantennary complex N-glycan	578:607	a biantennary complex N-glycan (G0)	578:612	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	4	5	theme	biantennary	580:590	arg1	G0					610:611	G0	610:611	G0	610:611	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	6	6	theme	domain	862:867	arg1	one					832:834	one	832:834	one	832:834	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	6	6	theme	domain	862:867	arg1	loops					845:849	these loops	839:849	these loops	839:849	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	6	6	theme	domain	862:867	arg1	domain					862:867	an SH3 domain	855:867	an SH3 domain	855:867	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	2	7	theme	only	322:325	arg1	α1,6-fucosyltransferase					284:306	A single human enzyme α1,6-fucosyltransferase	262:306	A single human enzyme α1,6-fucosyltransferase (FUT8)	262:313	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	7	theme	only	322:325	arg1	enzyme					327:332	the only enzyme	318:332	the only enzyme responsible for this modification	318:366	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	6	8	theme	SH3	858:860	arg1	domain					862:867	an SH3 domain	855:867	an SH3 domain	855:867	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	7	9	theme	inhibitor	1055:1063	arg1	design					1065:1070	inhibitor design	1055:1070	inhibitor design	1055:1070	This information serves as a framework for inhibitor design, and helps to assess its potential as a therapeutic target.
32080177	7	10	theme	therapeutic	1112:1122	arg1	potential					1097:1105	its potential	1093:1105	its potential	1093:1105	This information serves as a framework for inhibitor design, and helps to assess its potential as a therapeutic target.
32080177	7	10	theme	therapeutic	1112:1122	arg1	target					1124:1129	a therapeutic target	1110:1129	a therapeutic target	1110:1129	This information serves as a framework for inhibitor design, and helps to assess its potential as a therapeutic target.
32080177	3	11	theme	recognition	459:469	arg1	details					438:444	the details	434:444	the details of substrate recognition and catalysis by FUT8	434:491	To date, the details of substrate recognition and catalysis by FUT8 remain unknown.
32080177	5	12	theme	loops	739:743	arg1	series					729:734	a series	727:734	a series of loops and an α-helix which all contribute in forming the binding site	727:807	FUT8 follows an SN2 mechanism and deploys a series of loops and an α-helix which all contribute in forming the binding site.
32080177	5	13	theme	binding	796:802	arg1	site					804:807	the binding site	792:807	the binding site	792:807	FUT8 follows an SN2 mechanism and deploys a series of loops and an α-helix which all contribute in forming the binding site.
32080177	4	14	theme	substrate	648:656	arg1	recognition					658:668	substrate recognition	648:668	substrate recognition	648:668	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	2	15	link	α-1,6-linked	391:402	arg1	fucose					404:409	an α-1,6-linked fucose	388:409	an α-1,6-linked fucose	388:409	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	1	16	theme	innermost	203:211	arg1	residue					233:239	the innermost N-acetylglucosamine residue	199:239	the innermost N-acetylglucosamine residue of N-linked glycans	199:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	1	16	theme	innermost	203:211	arg1	glycans					253:259	N-linked glycans	244:259	N-linked glycans	244:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	0	17	theme	Structural	0:9	arg1	basis					11:15	Structural basis	0:15	Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase	0:82	Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase.
32080177	1	18	theme	essential	109:117	arg1	Core-fucosylation					85:101	Core-fucosylation	85:101	Core-fucosylation	85:101	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	1	18	theme	essential	109:117	arg1	modification					130:141	an essential biological modification	106:141	an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans	106:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	3	19	theme	substrate	449:457	arg1	recognition					459:469	substrate recognition	449:469	substrate recognition	449:469	To date, the details of substrate recognition and catalysis by FUT8 remain unknown.
32080177	0	20	theme	substrate	21:29	arg1	specificity					31:41	specificity	31:41	specificity	31:41	Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase.
32080177	5	21	theme	SN2	701:703	arg1	mechanism					705:713	an SN2 mechanism	698:713	an SN2 mechanism	698:713	FUT8 follows an SN2 mechanism and deploys a series of loops and an α-helix which all contribute in forming the binding site.
32080177	2	22	theme	responsible	334:344	arg1	α1,6-fucosyltransferase					284:306	A single human enzyme α1,6-fucosyltransferase	262:306	A single human enzyme α1,6-fucosyltransferase (FUT8)	262:313	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	22	theme	responsible	334:344	arg1	enzyme					327:332	the only enzyme	318:332	the only enzyme responsible for this modification	318:366	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	6	23	theme	sugars	917:922	arg1	recognition					893:903	the recognition	889:903	the recognition of branched sugars	889:922	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	6	24	theme	branched	908:915	arg1	sugars					917:922	branched sugars	908:922	branched sugars	908:922	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	3	25	theme	catalysis	475:483	arg1	details					438:444	the details	434:444	the details of substrate recognition and catalysis by FUT8	434:491	To date, the details of substrate recognition and catalysis by FUT8 remain unknown.
32080177	2	26	theme	human	271:275	arg1	α1,6-fucosyltransferase					284:306	A single human enzyme α1,6-fucosyltransferase	262:306	A single human enzyme α1,6-fucosyltransferase (FUT8)	262:313	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	26	theme	human	271:275	arg1	enzyme					327:332	the only enzyme	318:332	the only enzyme responsible for this modification	318:366	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	26	theme	human	271:275	arg1	FUT8					309:312	FUT8	309:312	FUT8	309:312	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	1	27	theme	N-acetylglucosamine	213:231	arg1	residue					233:239	the innermost N-acetylglucosamine residue	199:239	the innermost N-acetylglucosamine residue of N-linked glycans	199:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	1	27	theme	N-acetylglucosamine	213:231	arg1	glycans					253:259	N-linked glycans	244:259	N-linked glycans	244:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	1	28	theme	N-linked	244:251	arg1	glycans					253:259	N-linked glycans	244:259	N-linked glycans	244:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	2	29	theme	single	264:269	arg1	α1,6-fucosyltransferase					284:306	A single human enzyme α1,6-fucosyltransferase	262:306	A single human enzyme α1,6-fucosyltransferase (FUT8)	262:313	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	29	theme	single	264:269	arg1	enzyme					327:332	the only enzyme	318:332	the only enzyme responsible for this modification	318:366	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	29	theme	single	264:269	arg1	FUT8					309:312	FUT8	309:312	FUT8	309:312	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	1	30	theme	glycans	253:259	arg1	residue					233:239	the innermost N-acetylglucosamine residue	199:239	the innermost N-acetylglucosamine residue of N-linked glycans	199:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	1	30	theme	glycans	253:259	arg1	glycans					253:259	N-linked glycans	244:259	N-linked glycans	244:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	4	31	theme	FUT8	550:553	arg1	N-glycan					600:607	a biantennary complex N-glycan	578:607	a biantennary complex N-glycan (G0)	578:612	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	4	31	theme	FUT8	550:553	arg1	structure					537:545	the crystal structure	525:545	the crystal structure of FUT8 complexed with GDP	525:572	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	4	31	theme	FUT8	550:553	arg1	G0					610:611	G0	610:611	G0	610:611	Here, we report the crystal structure of FUT8 complexed with GDP and a biantennary complex N-glycan (G0), which provides insight into both substrate recognition and catalysis.
32080177	1	32	theme	biological	119:128	arg1	Core-fucosylation					85:101	Core-fucosylation	85:101	Core-fucosylation	85:101	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	1	32	theme	biological	119:128	arg1	modification					130:141	an essential biological modification	106:141	an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans	106:259	Core-fucosylation is an essential biological modification by which a fucose is transferred from GDP-β-L-fucose to the innermost N-acetylglucosamine residue of N-linked glycans.
32080177	2	33	theme	fucose	404:409	arg1	addition					376:383	the addition	372:383	the addition of an α-1,6-linked fucose to N-glycans	372:422	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	6	34	theme	arm	966:968	arg1	GlcNAc					970:975	the α1,3 arm GlcNAc	957:975	the α1,3 arm GlcNAc	957:975	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	6	34	theme	arm	966:968	arg1	feature					980:986	a feature	978:986	a feature required for catalysis	978:1009	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	0	35	theme	α1,6-fucosyltransferase	60:82	arg1	catalysis					47:55	catalysis	47:55	catalysis	47:55	Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase.
32080177	0	35	theme	α1,6-fucosyltransferase	60:82	arg1	specificity					31:41	specificity	31:41	specificity	31:41	Structural basis for substrate specificity and catalysis of α1,6-fucosyltransferase.
32080177	2	36	theme	enzyme	277:282	arg1	α1,6-fucosyltransferase					284:306	A single human enzyme α1,6-fucosyltransferase	262:306	A single human enzyme α1,6-fucosyltransferase (FUT8)	262:313	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	36	theme	enzyme	277:282	arg1	enzyme					327:332	the only enzyme	318:332	the only enzyme responsible for this modification	318:366	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	36	theme	enzyme	277:282	arg1	FUT8					309:312	FUT8	309:312	FUT8	309:312	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	2	37	theme	α-1,6-linked	391:402	arg1	fucose					404:409	an α-1,6-linked fucose	388:409	an α-1,6-linked fucose	388:409	A single human enzyme α1,6-fucosyltransferase (FUT8) is the only enzyme responsible for this modification via the addition of an α-1,6-linked fucose to N-glycans.
32080177	6	38	theme	α1,3	961:964	arg1	GlcNAc					970:975	the α1,3 arm GlcNAc	957:975	the α1,3 arm GlcNAc	957:975	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
32080177	6	38	theme	α1,3	961:964	arg1	feature					980:986	a feature	978:986	a feature required for catalysis	978:1009	An exosite, formed by one of these loops and an SH3 domain, is responsible for the recognition of branched sugars, making contacts specifically to the α1,3 arm GlcNAc, a feature required for catalysis.
33673983	4	0	theme	spectrometry	815:826	arg1	combination					705:715	The combination	701:715	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry	701:826	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	0	1	from	Identification	0:13	arg1	tricornutum					78:88	the diatom Phaeodactylum tricornutum	53:88	the diatom Phaeodactylum tricornutum	53:88	Identification of N-glycan oligomannoside isomers in the diatom Phaeodactylum tricornutum.
33673983	4	2	theme	N-linked	965:972	arg1	oligomannosides					949:963	the oligomannosides	945:963	the oligomannosides N-linked to proteins	945:984	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	4	3	theme	isomers	895:901	arg1	structure					863:871	the detailed structure	850:871	the detailed structure of the oligomannoside isomers	850:901	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	6	4	theme	expression	1196:1205	arg1	system					1207:1212	an alternative ecofriendly expression system	1169:1212	an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy	1169:1265	This represent an advantage as an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy.
33673983	6	4	theme	expression	1196:1205	arg1	advantage					1156:1164	an advantage	1153:1164	an advantage	1153:1164	This represent an advantage as an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy.
33673983	5	5	theme	other	1112:1116	arg1	species					1129:1135	other microalgae species	1112:1135	other microalgae species	1112:1135	Therefore, P. tricornutum synthesizes human-like oligomannosides in contrast to other microalgae species.
33673983	4	6	theme	oligomannoside	880:893	arg1	isomers					895:901	the oligomannoside isomers	876:901	the oligomannoside isomers	876:901	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	5	7	dep	species	1129:1135	arg1	contrast					1100:1107	contrast	1100:1107	contrast	1100:1107	Therefore, P. tricornutum synthesizes human-like oligomannosides in contrast to other microalgae species.
33673983	3	8	theme	diatom	591:596	arg1	tricornutum					612:622	the diatom Phaeodactylum tricornutum	587:622	the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	587:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	4	9	theme	ionization-multistage	781:801	arg1	spectrometry					815:826	electrospray ionization-multistage tandem mass spectrometry	768:826	electrospray ionization-multistage tandem mass spectrometry	768:826	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	4	10	link	N-linked	965:972	arg1	oligomannosides					949:963	the oligomannosides	945:963	the oligomannosides N-linked to proteins	945:984	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	3	11	theme	Phaeodactylum	598:610	arg1	tricornutum					612:622	the diatom Phaeodactylum tricornutum	587:622	the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	587:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	6	12	theme	human	1253:1257	arg1	therapy					1259:1265	human therapy	1253:1265	human therapy	1253:1265	This represent an advantage as an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy.
33673983	4	13	theme	Spectrometry	751:762	arg1	combination					705:715	The combination	701:715	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry	701:826	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	5	14	theme	human-like	1070:1079	arg1	oligomannosides					1081:1095	human-like oligomannosides	1070:1095	human-like oligomannosides	1070:1095	Therefore, P. tricornutum synthesizes human-like oligomannosides in contrast to other microalgae species.
33673983	2	15	theme	N-glycans	439:447	arg1	profiling					422:430	the profiling	418:430	the profiling of the N-glycans	418:447	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	1	16	theme	emerging	106:113	arg1	Microalgae					91:100	Microalgae	91:100	Microalgae	91:100	Microalgae are emerging production systems for recombinant proteins like monoclonal antibodies.
33673983	1	16	theme	emerging	106:113	arg1	systems					126:132	emerging production systems	106:132	emerging production systems for recombinant proteins like monoclonal antibodies	106:184	Microalgae are emerging production systems for recombinant proteins like monoclonal antibodies.
33673983	4	17	theme	electrospray	768:779	arg1	spectrometry					815:826	electrospray ionization-multistage tandem mass spectrometry	768:826	electrospray ionization-multistage tandem mass spectrometry	768:826	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	0	18	theme	oligomannoside	27:40	arg1	isomers					42:48	N-glycan oligomannoside isomers	18:48	N-glycan oligomannoside isomers	18:48	Identification of N-glycan oligomannoside isomers in the diatom Phaeodactylum tricornutum.
33673983	4	19	theme	detailed	854:861	arg1	structure					863:871	the detailed structure	850:871	the detailed structure of the oligomannoside isomers	850:901	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	4	20	theme	oligomannosides	949:963	arg1	processing					931:940	the processing	927:940	the processing of the oligomannosides N-linked to proteins	927:984	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	1	21	theme	production	115:124	arg1	Microalgae					91:100	Microalgae	91:100	Microalgae	91:100	Microalgae are emerging production systems for recombinant proteins like monoclonal antibodies.
33673983	1	21	theme	production	115:124	arg1	systems					126:132	emerging production systems	106:132	emerging production systems for recombinant proteins like monoclonal antibodies	106:184	Microalgae are emerging production systems for recombinant proteins like monoclonal antibodies.
33673983	4	22	theme	ion	720:722	arg1	Spectrometry					751:762	ion mobility spectrometry-mass Spectrometry	720:762	ion mobility spectrometry-mass Spectrometry	720:762	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	0	23	theme	N-glycan	18:25	arg1	isomers					42:48	N-glycan oligomannoside isomers	18:48	N-glycan oligomannoside isomers	18:48	Identification of N-glycan oligomannoside isomers in the diatom Phaeodactylum tricornutum.
33673983	5	24	theme	microalgae	1118:1127	arg1	species					1129:1135	other microalgae species	1112:1135	other microalgae species	1112:1135	Therefore, P. tricornutum synthesizes human-like oligomannosides in contrast to other microalgae species.
33673983	2	25	theme	glycoprotein-based	332:349	arg1	products					351:358	mainly glycoprotein-based products	325:358	mainly glycoprotein-based products	325:358	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	2	25	theme	glycoprotein-based	332:349	arg1	characterization					208:223	the characterization	204:223	the characterization	204:223	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	4	26	theme	mass	810:813	arg1	spectrometry					815:826	electrospray ionization-multistage tandem mass spectrometry	768:826	electrospray ionization-multistage tandem mass spectrometry	768:826	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	3	27	theme	N-linked	547:554	arg1	oligosaccharides					556:571	the protein N-linked oligosaccharides	535:571	the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	535:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	4	28	theme	spectrometry-mass	733:749	arg1	Spectrometry					751:762	ion mobility spectrometry-mass Spectrometry	720:762	ion mobility spectrometry-mass Spectrometry	720:762	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	3	29	theme	functional	667:676	arg1	antibodies					689:698	functional monoclonal antibodies	667:698	functional monoclonal antibodies	667:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	3	30	theme	N-glycosylation	499:513	arg1	pathway					515:521	its N-glycosylation pathway	495:521	its N-glycosylation pathway	495:521	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	0	31	theme	isomers	42:48	arg1	Identification					0:13	Identification	0:13	Identification of N-glycan oligomannoside isomers in the diatom Phaeodactylum tricornutum.	0:89	Identification of N-glycan oligomannoside isomers in the diatom Phaeodactylum tricornutum.
33673983	2	32	theme	machinery	258:266	arg1	products					351:358	mainly glycoprotein-based products	325:358	mainly glycoprotein-based products	325:358	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	2	32	theme	machinery	258:266	arg1	characterization					208:223	the characterization	204:223	the characterization	204:223	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	3	33	used	used	638:641	arg2	tricornutum					612:622	the diatom Phaeodactylum tricornutum	587:622	the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	587:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	0	34	theme	diatom	57:62	arg1	tricornutum					78:88	the diatom Phaeodactylum tricornutum	53:88	the diatom Phaeodactylum tricornutum	53:88	Identification of N-glycan oligomannoside isomers in the diatom Phaeodactylum tricornutum.
33673983	6	35	theme	ecofriendly	1184:1194	arg1	system					1207:1212	an alternative ecofriendly expression system	1169:1212	an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy	1169:1265	This represent an advantage as an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy.
33673983	6	35	theme	ecofriendly	1184:1194	arg1	advantage					1156:1164	an advantage	1153:1164	an advantage	1153:1164	This represent an advantage as an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy.
33673983	2	36	theme	N-glycosylation	242:256	arg1	machinery					258:266	the host cell N-glycosylation machinery	228:266	the host cell N-glycosylation machinery	228:266	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	3	37	theme	protein	539:545	arg1	oligosaccharides					556:571	the protein N-linked oligosaccharides	535:571	the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	535:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	2	38	theme	host	232:235	arg1	machinery					258:266	the host cell N-glycosylation machinery	228:266	the host cell N-glycosylation machinery	228:266	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	2	39	theme	cell	237:240	arg1	machinery					258:266	the host cell N-glycosylation machinery	228:266	the host cell N-glycosylation machinery	228:266	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	3	40	attach	isolated	573:580	arg1	tricornutum					612:622	the diatom Phaeodactylum tricornutum	587:622	the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	587:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	3	40	attach	isolated	573:580	arg2	oligosaccharides					556:571	the protein N-linked oligosaccharides	535:571	the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	535:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	1	41	theme	recombinant	138:148	arg1	proteins					150:157	recombinant proteins	138:157	recombinant proteins like monoclonal antibodies	138:184	Microalgae are emerging production systems for recombinant proteins like monoclonal antibodies.
33673983	2	42	theme	biopharmaceuticals	295:312	arg1	products					351:358	mainly glycoprotein-based products	325:358	mainly glycoprotein-based products	325:358	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	2	42	theme	biopharmaceuticals	295:312	arg1	characterization					208:223	the characterization	204:223	the characterization	204:223	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	3	43	theme	monoclonal	678:687	arg1	antibodies					689:698	functional monoclonal antibodies	667:698	functional monoclonal antibodies	667:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	2	44	theme	analytical	380:389	arg1	methodologies					391:403	efficient analytical methodologies	370:403	efficient analytical methodologies dedicated to the profiling of the N-glycans	370:447	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	6	45	theme	alternative	1172:1182	arg1	system					1207:1212	an alternative ecofriendly expression system	1169:1212	an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy	1169:1265	This represent an advantage as an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy.
33673983	6	45	theme	alternative	1172:1182	arg1	advantage					1156:1164	an advantage	1153:1164	an advantage	1153:1164	This represent an advantage as an alternative ecofriendly expression system to produce biopharmaceuticals used for human therapy.
33673983	3	46	link	N-linked	547:554	arg1	oligosaccharides					556:571	the protein N-linked oligosaccharides	535:571	the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies	535:698	Herein, in order to gain knowledge regarding its N-glycosylation pathway, we profile the protein N-linked oligosaccharides isolated from the diatom Phaeodactylum tricornutum that has been used successfully to produce functional monoclonal antibodies.
33673983	2	47	theme	microalgae-made	279:293	arg1	biopharmaceuticals					295:312	the microalgae-made biopharmaceuticals	275:312	the microalgae-made biopharmaceuticals	275:312	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	2	48	theme	efficient	370:378	arg1	methodologies					391:403	efficient analytical methodologies	370:403	efficient analytical methodologies dedicated to the profiling of the N-glycans	370:447	In this context, the characterization of the host cell N-glycosylation machinery and of the microalgae-made biopharmaceuticals, which are mainly glycoprotein-based products, requires efficient analytical methodologies dedicated to the profiling of the N-glycans.
33673983	4	49	theme	mobility	724:731	arg1	Spectrometry					751:762	ion mobility spectrometry-mass Spectrometry	720:762	ion mobility spectrometry-mass Spectrometry	720:762	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33673983	1	50	theme	monoclonal	164:173	arg1	antibodies					175:184	monoclonal antibodies	164:184	monoclonal antibodies	164:184	Microalgae are emerging production systems for recombinant proteins like monoclonal antibodies.
33673983	0	51	theme	Phaeodactylum	64:76	arg1	tricornutum					78:88	the diatom Phaeodactylum tricornutum	53:88	the diatom Phaeodactylum tricornutum	53:88	Identification of N-glycan oligomannoside isomers in the diatom Phaeodactylum tricornutum.
33673983	4	52	theme	tandem	803:808	arg1	spectrometry					815:826	electrospray ionization-multistage tandem mass spectrometry	768:826	electrospray ionization-multistage tandem mass spectrometry	768:826	The combination of ion mobility spectrometry-mass Spectrometry and electrospray ionization-multistage tandem mass spectrometry allows us to decipher the detailed structure of the oligomannoside isomers and to demonstrate that the processing of the oligomannosides N-linked to proteins occurs in this diatom as reported in mammals.
33908014	4	0	theme	PNGase	644:649	arg1	F					651:651	Rapid™ PNGase F	637:651	Rapid™ PNGase F (NEB #P0710)	637:664	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	0	theme	PNGase	644:649	arg1	P0710					659:663	NEB #P0710	654:663	NEB #P0710	654:663	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	3	1	theme	dimeric	560:566	arg1	proteins					575:582	dimeric fusion proteins	560:582	dimeric fusion proteins	560:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	4	2	theme	Rapid™	637:642	arg1	F					651:651	Rapid™ PNGase F	637:651	Rapid™ PNGase F (NEB #P0710)	637:664	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	2	theme	Rapid™	637:642	arg1	P0710					659:663	NEB #P0710	654:663	NEB #P0710	654:663	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	3	with	F	651:651	arg1	exoglycosidases					816:830	exoglycosidases	816:830	exoglycosidases	816:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	2	4	theme	oligosaccharide	320:334	arg1	end					310:312	the nonreducing end	294:312	the nonreducing end of an oligosaccharide	294:334	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	5	5	theme	overnight	953:961	arg1	analysis					944:951	CE analysis overnight	941:961	CE analysis overnight	941:961	This protocol is designed for completion within an 8 h time frame to allow for subsequent LC-FLD, LC-MS, or CE analysis overnight.
33908014	4	6	with	digestion	801:809	arg1	exoglycosidases					816:830	exoglycosidases	816:830	exoglycosidases	816:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	7	theme	glycans	773:779	arg1	F					651:651	Rapid™ PNGase F	637:651	Rapid™ PNGase F (NEB #P0710)	637:664	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	7	theme	glycans	773:779	arg1	labeling					674:681	direct labeling	667:681	direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB)	667:751	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	7	theme	glycans	773:779	arg1	P0710					659:663	NEB #P0710	654:663	NEB #P0710	654:663	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	7	theme	glycans	773:779	arg1	digestion					801:809	a 3 h enzymatic digestion	785:809	a 3 h enzymatic digestion with exoglycosidases	785:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	7	theme	glycans	773:779	arg1	cleanup					754:760	cleanup	754:760	cleanup of labeled glycans	754:779	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	3	8	theme	Fc	520:521	arg1	domain					523:528	the Fc domain	516:528	the Fc domain of therapeutic antibodies and dimeric fusion proteins	516:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	8	theme	Fc	520:521	arg1	antibodies					545:554	therapeutic antibodies	533:554	therapeutic antibodies	533:554	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	8	theme	Fc	520:521	arg1	proteins					575:582	dimeric fusion proteins	560:582	dimeric fusion proteins	560:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	4	9	theme	3 h	787:789	arg1	digestion					801:809	a 3 h enzymatic digestion	785:809	a 3 h enzymatic digestion with exoglycosidases	785:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	3	10	theme	exoglycosidases	463:477	arg1	combinations					447:458	combinations	447:458	combinations of exoglycosidases	447:477	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	1	11	theme	CE	167:168	arg1	analysis					170:177	CE analysis	167:177	CE analysis	167:177	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	5	12	theme	subsequent	912:921	arg1	LC-FLD					923:928	subsequent LC-FLD	912:928	subsequent LC-FLD	912:928	This protocol is designed for completion within an 8 h time frame to allow for subsequent LC-FLD, LC-MS, or CE analysis overnight.
33908014	4	13	theme	released	686:693	arg1	glycans					695:701	released glycans	686:701	released glycans with procainamide (PCA) or 2-aminobenzamide (2AB)	686:751	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	2	14	dep	linkage	368:374	arg1	the					364:366	the	364:366	the	364:366	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	2	15	theme	carbon	427:432	arg1	configuration					397:409	configuration	397:409	configuration	397:409	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	2	15	theme	carbon	427:432	arg1	stereochemistry					377:391	stereochemistry	377:391	stereochemistry	377:391	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	2	15	theme	carbon	427:432	arg1	linkage					368:374	linkage	368:374	linkage	368:374	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	4	16	theme	glycan	617:622	arg1	release					624:630	glycan release	617:630	glycan release	617:630	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	1	17	theme	sequential	82:91	arg1	digestion					108:116	sequential exoglycosidase digestion	82:116	sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis	82:177	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	2	18	theme	anomeric	418:425	arg1	carbon					427:432	the anomeric carbon	414:432	the anomeric carbon	414:432	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	1	19	theme	exoglycosidase	93:106	arg1	digestion					108:116	sequential exoglycosidase digestion	82:116	sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis	82:177	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	1	20	theme	carbohydrate	197:208	arg1	information					221:231	detailed carbohydrate structural information	188:231	detailed carbohydrate structural information	188:231	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	0	21	theme	Exoglycosidases	7:21	arg1	Use					0:2	Use	0:2	Use of Exoglycosidases for the Structural Characterization of Glycans	0:68	Use of Exoglycosidases for the Structural Characterization of Glycans.
33908014	5	22	theme	CE	941:942	arg1	analysis					944:951	CE analysis overnight	941:961	CE analysis overnight	941:961	This protocol is designed for completion within an 8 h time frame to allow for subsequent LC-FLD, LC-MS, or CE analysis overnight.
33908014	1	23	theme	digestion	108:116	arg1	use					75:77	The use	71:77	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis	71:177	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	1	24	theme	structural	210:219	arg1	information					221:231	detailed carbohydrate structural information	188:231	detailed carbohydrate structural information	188:231	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	0	25	theme	Structural	31:40	arg1	Characterization					42:57	the Structural Characterization	27:57	the Structural Characterization of Glycans	27:68	Use of Exoglycosidases for the Structural Characterization of Glycans.
33908014	3	26	theme	antibodies	545:554	arg1	domain					523:528	the Fc domain	516:528	the Fc domain of therapeutic antibodies and dimeric fusion proteins	516:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	26	theme	antibodies	545:554	arg1	antibodies					545:554	therapeutic antibodies	533:554	therapeutic antibodies	533:554	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	26	theme	antibodies	545:554	arg1	proteins					575:582	dimeric fusion proteins	560:582	dimeric fusion proteins	560:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	1	27	theme	detailed	188:195	arg1	information					221:231	detailed carbohydrate structural information	188:231	detailed carbohydrate structural information	188:231	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	4	28	theme	glycans	695:701	arg1	F					651:651	Rapid™ PNGase F	637:651	Rapid™ PNGase F (NEB #P0710)	637:664	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	28	theme	glycans	695:701	arg1	labeling					674:681	direct labeling	667:681	direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB)	667:751	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	28	theme	glycans	695:701	arg1	P0710					659:663	NEB #P0710	654:663	NEB #P0710	654:663	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	28	theme	glycans	695:701	arg1	digestion					801:809	a 3 h enzymatic digestion	785:809	a 3 h enzymatic digestion with exoglycosidases	785:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	28	theme	glycans	695:701	arg1	cleanup					754:760	cleanup	754:760	cleanup of labeled glycans	754:779	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	5	29	theme	time	888:891	arg1	frame					893:897	an 8 h time frame	881:897	an 8 h time frame to allow for subsequent LC-FLD, LC-MS, or CE analysis overnight	881:961	This protocol is designed for completion within an 8 h time frame to allow for subsequent LC-FLD, LC-MS, or CE analysis overnight.
33908014	4	30	with	glycans	695:701	arg1	2AB					748:750	2AB	748:750	2AB	748:750	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	30	with	glycans	695:701	arg1	PCA					722:724	PCA	722:724	PCA	722:724	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	30	with	glycans	695:701	arg1	2-aminobenzamide					730:745	2-aminobenzamide	730:745	2-aminobenzamide (2AB)	730:751	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	30	with	glycans	695:701	arg1	procainamide					708:719	procainamide	708:719	procainamide (PCA)	708:725	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	3	31	from	glycans	505:511	arg1	domain					523:528	the Fc domain	516:528	the Fc domain of therapeutic antibodies and dimeric fusion proteins	516:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	31	from	glycans	505:511	arg1	antibodies					545:554	therapeutic antibodies	533:554	therapeutic antibodies	533:554	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	31	from	glycans	505:511	arg1	proteins					575:582	dimeric fusion proteins	560:582	dimeric fusion proteins	560:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	4	32	theme	labeled	765:771	arg1	glycans					773:779	labeled glycans	765:779	labeled glycans	765:779	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	2	33	theme	specific	241:248	arg1	exoglycosidases					250:264	Highly specific exoglycosidases	234:264	Highly specific exoglycosidases	234:264	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	3	34	theme	therapeutic	533:543	arg1	antibodies					545:554	therapeutic antibodies	533:554	therapeutic antibodies	533:554	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	4	35	with	cleanup	754:760	arg1	exoglycosidases					816:830	exoglycosidases	816:830	exoglycosidases	816:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	1	36	theme	oligosaccharides	121:136	arg1	digestion					108:116	sequential exoglycosidase digestion	82:116	sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis	82:177	The use of sequential exoglycosidase digestion of oligosaccharides followed by LC-FLD, LC-MS or CE analysis provides detailed carbohydrate structural information.
33908014	4	37	with	labeling	674:681	arg1	exoglycosidases					816:830	exoglycosidases	816:830	exoglycosidases	816:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	2	38	theme	nonreducing	298:308	arg1	end					310:312	the nonreducing end	294:312	the nonreducing end of an oligosaccharide	294:334	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	2	39	from	end	310:312	arg1	monosaccharides					273:287	monosaccharides	273:287	monosaccharides from the nonreducing end of an oligosaccharide	273:334	Highly specific exoglycosidases cleave monosaccharides from the nonreducing end of an oligosaccharide and yield information about the linkage, stereochemistry and configuration of the anomeric carbon.
33908014	4	40	theme	#	658:658	arg1	F					651:651	Rapid™ PNGase F	637:651	Rapid™ PNGase F (NEB #P0710)	637:664	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	40	theme	#	658:658	arg1	P0710					659:663	NEB #P0710	654:663	NEB #P0710	654:663	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	41	theme	enzymatic	791:799	arg1	digestion					801:809	a 3 h enzymatic digestion	785:809	a 3 h enzymatic digestion with exoglycosidases	785:830	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	42	theme	NEB	654:656	arg1	F					651:651	Rapid™ PNGase F	637:651	Rapid™ PNGase F (NEB #P0710)	637:664	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	42	theme	NEB	654:656	arg1	P0710					659:663	NEB #P0710	654:663	NEB #P0710	654:663	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	4	43	theme	direct	667:672	arg1	labeling					674:681	direct labeling	667:681	direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB)	667:751	The workflow described includes glycan release with Rapid™ PNGase F (NEB #P0710), direct labeling of released glycans with procainamide (PCA) or 2-aminobenzamide (2AB), cleanup of labeled glycans and a 3 h enzymatic digestion with exoglycosidases.
33908014	3	44	theme	fusion	568:573	arg1	proteins					575:582	dimeric fusion proteins	560:582	dimeric fusion proteins	560:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	5	45	theme	8 h	884:886	arg1	frame					893:897	an 8 h time frame	881:897	an 8 h time frame to allow for subsequent LC-FLD, LC-MS, or CE analysis overnight	881:961	This protocol is designed for completion within an 8 h time frame to allow for subsequent LC-FLD, LC-MS, or CE analysis overnight.
33908014	0	46	theme	Glycans	62:68	arg1	Characterization					42:57	the Structural Characterization	27:57	the Structural Characterization of Glycans	27:68	Use of Exoglycosidases for the Structural Characterization of Glycans.
33908014	3	47	theme	proteins	575:582	arg1	domain					523:528	the Fc domain	516:528	the Fc domain of therapeutic antibodies and dimeric fusion proteins	516:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	47	theme	proteins	575:582	arg1	antibodies					545:554	therapeutic antibodies	533:554	therapeutic antibodies	533:554	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
33908014	3	47	theme	proteins	575:582	arg1	proteins					575:582	dimeric fusion proteins	560:582	dimeric fusion proteins	560:582	Here we use combinations of exoglycosidases to precisely characterize glycans on the Fc domain of therapeutic antibodies and dimeric fusion proteins.
34687015	8	0	theme	Glycomic	1094:1101	arg1	alterations					1103:1113	Glycomic alterations	1094:1113	Glycomic alterations associated with inflammatory diseases	1094:1151	Glycomic alterations associated with inflammatory diseases often precede disease onset and follow remission.
34687015	3	1	attach	present	426:432	arg1	addition					398:405	addition	398:405	addition	398:405	In addition, the structure can present core-linked fucose and/or a bisecting GlcNAc.
34687015	3	1	attach	present	426:432	arg2	structure					412:420	the structure	408:420	the structure	408:420	In addition, the structure can present core-linked fucose and/or a bisecting GlcNAc.
34687015	10	2	theme	lectin	1431:1436	arg1	receptors					1438:1446	lectin receptors	1431:1446	lectin receptors	1431:1446	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	11	3	theme	glycomic	1541:1548	arg1	changes					1550:1556	the glycomic changes	1537:1556	the glycomic changes associated with inflammation and aging	1537:1595	The complex molecular bases of the glycomic changes associated with inflammation and aging are still poorly understood.
34687015	3	4	theme	bisecting	462:470	arg1	GlcNAc					472:477	a bisecting GlcNAc	460:477	a bisecting GlcNAc	460:477	In addition, the structure can present core-linked fucose and/or a bisecting GlcNAc.
34687015	10	5	theme	autoantibody	1481:1492	arg1	reactivity					1494:1503	autoantibody reactivity	1481:1503	autoantibody reactivity	1481:1503	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	7	6	theme	aging	1061:1065	arg1	case					1053:1056	the case	1049:1056	the case of aging	1049:1065	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	7	7	theme	above-mentioned	931:945	arg1	conditions					960:969	the above-mentioned pathological conditions	927:969	the above-mentioned pathological conditions	927:969	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	4	8	theme	glycans	719:725	arg1	expression					705:714	increased expression	695:714	increased expression of glycans terminating with GlcNAc	695:749	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	4	9	theme	increased	695:703	arg1	expression					705:714	increased expression	695:714	increased expression of glycans terminating with GlcNAc	695:749	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	1	10	theme	biological	164:173	arg1	interactions					175:186	biological interactions	164:186	biological interactions	164:186	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	10	11	theme	complement	1375:1384	arg1	activation					1386:1395	complement activation	1375:1395	complement activation	1375:1395	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	2	12	dep	galactose	323:331	arg1	residues					349:356	residues	349:356	residues	349:356	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	10	13	from	activation	1386:1395	arg1	cells					1470:1474	antigen-presenting cells	1451:1474	antigen-presenting cells	1451:1474	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	8	14	theme	inflammatory	1131:1142	arg1	diseases					1144:1151	inflammatory diseases	1131:1151	inflammatory diseases	1131:1151	Glycomic alterations associated with inflammatory diseases often precede disease onset and follow remission.
34687015	5	15	theme	core-fucose	796:806	arg1	presence					784:791	the presence	780:791	the presence of core-fucose and bisecting GlcNAc	780:827	These conditions alter also the presence of core-fucose and bisecting GlcNAc.
34687015	2	16	theme	chains	259:264	arg1	297					233:235	The asparagine 297	218:235	The asparagine 297 (Asn297) of IgG heavy chains	218:264	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	2	16	theme	chains	259:264	arg1	Asn297					238:243	Asn297	238:243	Asn297	238:243	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	9	17	gly	glycosylated	1218:1229	arg1	glycans					1235:1241	The aberrantly glycosylated IgG glycans	1203:1241	The aberrantly glycosylated IgG glycans associated with inflammation and aging	1203:1280	The aberrantly glycosylated IgG glycans associated with inflammation and aging can sustain inflammation through different mechanisms, fueling a vicious loop.
34687015	1	18	theme	interactions	175:186	arg1	one					191:193	one	191:193	one	191:193	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	1	18	theme	interactions	175:186	arg1	regulation					150:159	the fine regulation	141:159	the fine regulation of biological interactions	141:186	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	1	18	theme	interactions	175:186	arg1	the					198:200	the	198:200	the	198:200	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	6	19	theme	glycomic	851:858	arg1	alterations					860:870	similar glycomic alterations	843:870	similar glycomic alterations	843:870	Importantly, similar glycomic alterations are observed in aging.
34687015	2	20	dep	2	392:392	arg1	to					389:390	to	389:390	to	389:390	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	11	21	theme	complex	1510:1516	arg1	bases					1528:1532	The complex molecular bases	1506:1532	The complex molecular bases of the glycomic changes associated with inflammation and aging	1506:1595	The complex molecular bases of the glycomic changes associated with inflammation and aging are still poorly understood.
34687015	2	22	theme	heavy	253:257	arg1	chains					259:264	IgG heavy chains	249:264	IgG heavy chains	249:264	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	6	23	theme	similar	843:849	arg1	alterations					860:870	similar glycomic alterations	843:870	similar glycomic alterations	843:870	Importantly, similar glycomic alterations are observed in aging.
34687015	10	24	theme	antigen-presenting	1451:1468	arg1	cells					1470:1474	antigen-presenting cells	1451:1474	antigen-presenting cells	1451:1474	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	1	25	theme	multiple	93:100	arg1	roles					102:106	the multiple roles	89:106	the multiple roles played by protein glycosylation	89:138	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	7	26	dep	low-grade	987:995	arg1	asymptomatic					1007:1018	asymptomatic	1007:1018	asymptomatic	1007:1018	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	7	26	dep	low-grade	987:995	arg1	chronic					998:1004	chronic	998:1004	chronic	998:1004	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	4	27	theme	Asn297-linked	614:626	arg1	glycan					628:633	the IgG Asn297-linked glycan	606:633	the IgG Asn297-linked glycan	606:633	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	0	28	theme	Immunoglobulin	0:13	arg1	G					15:15	Immunoglobulin G	0:15	Immunoglobulin G	0:15	Immunoglobulin G Glycosylation Changes in Aging and Other Inflammatory Conditions.
34687015	10	29	theme	Fcγ	1398:1400	arg1	binding					1411:1417	Fcγ receptor binding	1398:1417	Fcγ receptor binding	1398:1417	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	9	30	theme	different	1315:1323	arg1	mechanisms					1325:1334	different mechanisms	1315:1334	different mechanisms	1315:1334	The aberrantly glycosylated IgG glycans associated with inflammation and aging can sustain inflammation through different mechanisms, fueling a vicious loop.
34687015	10	31	theme	receptor	1402:1409	arg1	binding					1411:1417	Fcγ receptor binding	1398:1417	Fcγ receptor binding	1398:1417	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	2	32	theme	diantennary	284:294	arg1	glycan					296:301	a diantennary glycan	282:301	a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2	282:392	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	4	33	theme	IgG	610:612	arg1	glycan					628:633	the IgG Asn297-linked glycan	606:633	the IgG Asn297-linked glycan	606:633	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	8	34	theme	disease	1167:1173	arg1	onset					1175:1179	disease onset	1167:1179	disease onset	1167:1179	Glycomic alterations associated with inflammatory diseases often precede disease onset and follow remission.
34687015	4	35	theme	autoimmune	505:514	arg1	conditions					516:525	many inflammatory and autoimmune conditions	483:525	many inflammatory and autoimmune conditions	483:525	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	7	36	theme	common	899:904	arg1	condition					906:914	The common condition	895:914	The common condition	895:914	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	7	36	theme	common	899:904	arg1	state					1033:1037	a low-grade, chronic, asymptomatic inflammatory state	985:1037	a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging	985:1091	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	1	37	theme	the	198:200	arg1	one					191:193	one	191:193	one	191:193	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	1	37	theme	the	198:200	arg1	regulation					150:159	the fine regulation	141:159	the fine regulation of biological interactions	141:186	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	1	37	theme	the	198:200	arg1	the					198:200	the	198:200	the	198:200	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	2	38	theme	galactose	323:331	arg1	number					313:318	a number	311:318	a number of galactose and sialic acid residues	311:356	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	1	39	theme	fine	145:148	arg1	one					191:193	one	191:193	one	191:193	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	1	39	theme	fine	145:148	arg1	regulation					150:159	the fine regulation	141:159	the fine regulation of biological interactions	141:186	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	1	39	theme	fine	145:148	arg1	the					198:200	the	198:200	the	198:200	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	7	40	theme	inflammatory	1020:1031	arg1	condition					906:914	The common condition	895:914	The common condition	895:914	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	7	40	theme	inflammatory	1020:1031	arg1	state					1033:1037	a low-grade, chronic, asymptomatic inflammatory state	985:1037	a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging	985:1091	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	7	40	theme	inflammatory	1020:1031	arg1	inflammaging					1080:1091	inflammaging	1080:1091	inflammaging	1080:1091	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	4	41	link	Asn297-linked	614:626	arg1	glycan					628:633	the IgG Asn297-linked glycan	606:633	the IgG Asn297-linked glycan	606:633	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	6	42	located	observed	876:883	arg1	aging					888:892	aging	888:892	aging	888:892	Importantly, similar glycomic alterations are observed in aging.
34687015	6	42	located	observed	876:883	arg2	alterations					860:870	similar glycomic alterations	843:870	similar glycomic alterations	843:870	Importantly, similar glycomic alterations are observed in aging.
34687015	5	43	theme	GlcNAc	822:827	arg1	presence					784:791	the presence	780:791	the presence of core-fucose and bisecting GlcNAc	780:827	These conditions alter also the presence of core-fucose and bisecting GlcNAc.
34687015	4	44	theme	many	483:486	arg1	conditions					516:525	many inflammatory and autoimmune conditions	483:525	many inflammatory and autoimmune conditions	483:525	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	4	45	theme	neoplastic	585:594	arg1	diseases					596:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	0	46	theme	Inflammatory	58:69	arg1	Conditions					71:80	Other Inflammatory Conditions	52:80	Other Inflammatory Conditions	52:80	Immunoglobulin G Glycosylation Changes in Aging and Other Inflammatory Conditions.
34687015	9	47	theme	vicious	1347:1353	arg1	loop					1355:1358	a vicious loop	1345:1358	a vicious loop	1345:1358	The aberrantly glycosylated IgG glycans associated with inflammation and aging can sustain inflammation through different mechanisms, fueling a vicious loop.
34687015	9	48	theme	glycosylated	1218:1229	arg1	glycans					1235:1241	The aberrantly glycosylated IgG glycans	1203:1241	The aberrantly glycosylated IgG glycans associated with inflammation and aging	1203:1280	The aberrantly glycosylated IgG glycans associated with inflammation and aging can sustain inflammation through different mechanisms, fueling a vicious loop.
34687015	2	49	theme	asparagine	222:231	arg1	297					233:235	The asparagine 297	218:235	The asparagine 297 (Asn297) of IgG heavy chains	218:264	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	2	49	theme	asparagine	222:231	arg1	Asn297					238:243	Asn297	238:243	Asn297	238:243	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	7	50	theme	low-grade	987:995	arg1	condition					906:914	The common condition	895:914	The common condition	895:914	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	7	50	theme	low-grade	987:995	arg1	state					1033:1037	a low-grade, chronic, asymptomatic inflammatory state	985:1037	a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging	985:1091	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	7	50	theme	low-grade	987:995	arg1	inflammaging					1080:1091	inflammaging	1080:1091	inflammaging	1080:1091	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	1	51	theme	protein	118:124	arg1	glycosylation					126:138	protein glycosylation	118:138	protein glycosylation	118:138	Among the multiple roles played by protein glycosylation, the fine regulation of biological interactions is one of the most important.
34687015	0	52	theme	Other	52:56	arg1	Conditions					71:80	Other Inflammatory Conditions	52:80	Other Inflammatory Conditions	52:80	Immunoglobulin G Glycosylation Changes in Aging and Other Inflammatory Conditions.
34687015	3	53	link	core-linked	434:444	arg1	fucose					446:451	core-linked fucose	434:451	core-linked fucose	434:451	In addition, the structure can present core-linked fucose and/or a bisecting GlcNAc.
34687015	9	54	theme	IgG	1231:1233	arg1	glycans					1235:1241	The aberrantly glycosylated IgG glycans	1203:1241	The aberrantly glycosylated IgG glycans associated with inflammation and aging	1203:1280	The aberrantly glycosylated IgG glycans associated with inflammation and aging can sustain inflammation through different mechanisms, fueling a vicious loop.
34687015	4	55	theme	inflammatory	488:499	arg1	conditions					516:525	many inflammatory and autoimmune conditions	483:525	many inflammatory and autoimmune conditions	483:525	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	11	56	theme	changes	1550:1556	arg1	bases					1528:1532	The complex molecular bases	1506:1532	The complex molecular bases of the glycomic changes associated with inflammation and aging	1506:1595	The complex molecular bases of the glycomic changes associated with inflammation and aging are still poorly understood.
34687015	10	57	from	binding	1420:1426	arg1	cells					1470:1474	antigen-presenting cells	1451:1474	antigen-presenting cells	1451:1474	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	4	58	theme	cardiovascular	553:566	arg1	diseases					596:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	3	59	theme	core-linked	434:444	arg1	fucose					446:451	core-linked fucose	434:451	core-linked fucose	434:451	In addition, the structure can present core-linked fucose and/or a bisecting GlcNAc.
34687015	5	60	theme	bisecting	812:820	arg1	GlcNAc					822:827	bisecting GlcNAc	812:827	bisecting GlcNAc	812:827	These conditions alter also the presence of core-fucose and bisecting GlcNAc.
34687015	10	61	from	binding	1411:1417	arg1	cells					1470:1474	antigen-presenting cells	1451:1474	antigen-presenting cells	1451:1474	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
34687015	2	62	theme	acid	344:347	arg1	number					313:318	a number	311:318	a number of galactose and sialic acid residues	311:356	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	4	63	theme	infectious	569:578	arg1	diseases					596:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	4	64	theme	metabolic	542:550	arg1	diseases					596:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	metabolic, cardiovascular, infectious, and neoplastic diseases	542:603	In many inflammatory and autoimmune conditions, as well as in metabolic, cardiovascular, infectious, and neoplastic diseases, the IgG Asn297-linked glycan becomes less sialylated and less galactosylated, leading to increased expression of glycans terminating with GlcNAc.
34687015	7	65	theme	pathological	947:958	arg1	conditions					960:969	the above-mentioned pathological conditions	927:969	the above-mentioned pathological conditions	927:969	The common condition, shared by the above-mentioned pathological conditions and aging, is a low-grade, chronic, asymptomatic inflammatory state which, in the case of aging, is known as inflammaging.
34687015	2	66	theme	sialic	337:342	arg1	acid					344:347	sialic acid	337:347	sialic acid	337:347	The asparagine 297 (Asn297) of IgG heavy chains is decorated by a diantennary glycan bearing a number of galactose and sialic acid residues on the branches ranging from 0 to 2.
34687015	11	67	theme	molecular	1518:1526	arg1	bases					1528:1532	The complex molecular bases	1506:1532	The complex molecular bases of the glycomic changes associated with inflammation and aging	1506:1595	The complex molecular bases of the glycomic changes associated with inflammation and aging are still poorly understood.
34687015	10	68	from	reactivity	1494:1503	arg1	cells					1470:1474	antigen-presenting cells	1451:1474	antigen-presenting cells	1451:1474	These include complement activation, Fcγ receptor binding, binding to lectin receptors on antigen-presenting cells, and autoantibody reactivity.
33177111	6	0	theme	Ser/Thr-rich	825:836	arg1	domain					838:843	a Ser/Thr-rich domain	823:843	a Ser/Thr-rich domain	823:843	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	6	0	theme	Ser/Thr-rich	825:836	arg1	O-glycosylated					879:892	O-glycosylated	879:892	O-glycosylated	879:892	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	10	1	theme	immune	1792:1797	arg1	evasion					1799:1805	CD55-mediated immune evasion	1778:1805	CD55-mediated immune evasion	1778:1805	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	1	2	theme	cells	257:261	arg1	behavior					239:246	the behavior	235:246	the behavior of tumor cells	235:261	Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells.
33177111	10	3	theme	immune	1647:1652	arg1	molecule					1665:1672	an immune checkpoint molecule	1644:1672	an immune checkpoint molecule for cancer cells	1644:1689	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	9	4	theme	breast	1464:1469	arg1	cells					1478:1482	breast cancer cells	1464:1482	breast cancer cells	1464:1482	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	8	5	theme	nonsialylated	1193:1205	arg1	core					1207:1210	nonsialylated core 1	1193:1212	nonsialylated core 1	1193:1212	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	4	6	theme	ST3GAL1	650:656	arg1	proteins					638:645	the potential target proteins	617:645	the potential target proteins of ST3GAL1	617:656	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	9	7	theme	complement-mediated	1435:1453	arg1	lysis					1455:1459	complement-mediated lysis	1435:1459	complement-mediated lysis	1435:1459	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	9	8	theme	cells	1478:1482	arg1	deposition					1420:1429	increased C3 deposition	1407:1429	increased C3 deposition	1407:1429	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	9	8	theme	cells	1478:1482	arg1	lysis					1455:1459	complement-mediated lysis	1435:1459	complement-mediated lysis	1435:1459	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	8	9	theme	disialylated	1262:1273	arg1	structure					1282:1290	the disialylated core 2 structure	1258:1290	the disialylated core 2 structure	1258:1290	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	10	10	theme	cancer	1678:1683	arg1	cells					1685:1689	cancer cells	1678:1689	cancer cells	1678:1689	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	1	11	gly	glycoproteins	210:222	arg1	glycoproteins					210:222	glycoproteins	210:222	glycoproteins	210:222	Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells.
33177111	6	12	theme	glycosylation	789:801	arg1	site					803:806	one N-linked glycosylation site	776:806	one N-linked glycosylation site	776:806	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	8	13	theme	monosialylated	1218:1231	arg1	core					1233:1236	monosialylated core 2	1218:1238	monosialylated core 2	1218:1238	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	4	14	theme	potential	621:629	arg1	proteins					638:645	the potential target proteins	617:645	the potential target proteins of ST3GAL1	617:656	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	6	15	gly	glycosylation	789:801	arg2	one					776:778	one	776:778	one	776:778	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	6	15	gly	glycosylation	789:801	arg2	site					803:806	one N-linked glycosylation site	776:806	one N-linked glycosylation site	776:806	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	4	16	theme	proteins	638:645	arg1	proteins					638:645	the potential target proteins	617:645	the potential target proteins of ST3GAL1	617:656	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	4	16	theme	proteins	638:645	arg1	one					610:612	one	610:612	one	610:612	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	10	17	theme	immune	1700:1705	arg1	attack					1707:1712	immune attack	1700:1712	immune attack	1700:1712	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	7	18	theme	mass	1035:1038	arg1	spectrometry					1040:1051	tandem mass spectrometry	1028:1051	tandem mass spectrometry	1028:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	9	19	theme	cell-mediated	1531:1543	arg1	cytotoxicity					1545:1556	antibody-dependent cell-mediated cytotoxicity	1512:1556	antibody-dependent cell-mediated cytotoxicity	1512:1556	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	7	20	theme	N-glycan	1071:1078	arg1	profile					1080:1086	the N-glycan profile	1067:1086	the N-glycan profile	1067:1086	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	5	21	theme	complement	680:689	arg1	protein					702:708	an important complement regulatory protein	667:708	an important complement regulatory protein	667:708	CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity.
33177111	5	21	theme	complement	680:689	arg1	CD55					659:662	CD55	659:662	CD55	659:662	CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity.
33177111	7	22	theme	cancer	1012:1017	arg1	cells					1019:1023	scramble or ST3GAL1 siRNA-treated breast cancer cells	971:1023	cells	1019:1023	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	10	23	theme	potential	1750:1758	arg1	inhibition					1723:1732	inhibition	1723:1732	inhibition of ST3GAL1	1723:1743	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	10	23	theme	potential	1750:1758	arg1	strategy					1760:1767	a potential strategy	1748:1767	a potential strategy to block CD55-mediated immune evasion	1748:1805	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	7	24	theme	siRNA-treated	991:1003	arg1	cells					1019:1023	scramble or ST3GAL1 siRNA-treated breast cancer cells	971:1023	cells	1019:1023	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	7	25	theme	CD55	952:955	arg1	N-					916:917	N-	916:917	N-	916:917	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	7	25	theme	CD55	952:955	arg1	oligosaccharides					932:947	O-linked oligosaccharides	923:947	O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry	923:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	1	26	theme	Altered	69:75	arg1	glycosylations					77:90	Altered glycosylations	69:90	Altered glycosylations	69:90	Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells.
33177111	7	27	attach	released	957:964	arg2	oligosaccharides					932:947	O-linked oligosaccharides	923:947	O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry	923:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	7	27	attach	released	957:964	arg1	cells					1019:1023	scramble or ST3GAL1 siRNA-treated breast cancer cells	971:1023	cells	1019:1023	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	3	28	theme	ST3GAL1	420:426	arg1	overexpression					402:415	overexpression	402:415	overexpression of ST3GAL1	402:426	In breast carcinomas, overexpression of ST3GAL1 promotes tumorigenesis and correlates with increased tumor grade.
33177111	7	29	theme	oligosaccharides	932:947	arg1	analyses					904:911	Detailed analyses	895:911	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry	895:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	6	30	contain	had	772:774	arg1	CD55					767:770	CD55	767:770	CD55	767:770	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	6	30	contain	had	772:774	arg2	site					803:806	one N-linked glycosylation site	776:806	one N-linked glycosylation site	776:806	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	6	31	dep	domain	838:843	arg1	addition					811:818	addition	811:818	addition	811:818	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	3	32	theme	increased	471:479	arg1	grade					487:491	increased tumor grade	471:491	increased tumor grade	471:491	In breast carcinomas, overexpression of ST3GAL1 promotes tumorigenesis and correlates with increased tumor grade.
33177111	0	33	theme	CD55	15:18	arg1	Sialylation					0:10	Sialylation	0:10	Sialylation of CD55 by ST3GAL1	0:29	Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer.
33177111	9	34	theme	CD55	1369:1372	arg1	desialylation					1352:1364	O-linked desialylation	1343:1364	O-linked desialylation of CD55 by ST3GAL1 silencing	1343:1393	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	8	35	from	shift	1171:1175	arg1	abundance					1180:1188	abundance	1180:1188	abundance	1180:1188	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	4	36	theme	knockdown	566:574	arg1	ST3GAL1					576:582	knockdown ST3GAL1	566:582	knockdown ST3GAL1	566:582	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	9	37	theme	ST3GAL1	1377:1383	arg1	silencing					1385:1393	ST3GAL1 silencing	1377:1393	ST3GAL1 silencing	1377:1393	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	10	38	theme	O-linked	1605:1612	arg1	sialylation					1614:1624	ST3GAL1-mediated O-linked sialylation	1588:1624	ST3GAL1-mediated O-linked sialylation of CD55	1588:1632	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	10	39	theme	CD55-mediated	1778:1790	arg1	evasion					1799:1805	CD55-mediated immune evasion	1778:1805	CD55-mediated immune evasion	1778:1805	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	0	40	theme	Immune	43:48	arg1	Evasion					50:56	Immune Evasion	43:56	Immune Evasion in Cancer	43:66	Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer.
33177111	7	41	theme	O-linked	923:930	arg1	oligosaccharides					932:947	O-linked oligosaccharides	923:947	O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry	923:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	9	42	theme	increased	1407:1415	arg1	deposition					1420:1429	increased C3 deposition	1407:1429	increased C3 deposition	1407:1429	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	7	43	link	O-linked	923:930	arg1	oligosaccharides					932:947	O-linked oligosaccharides	923:947	O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry	923:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	2	44	theme	chain	363:367	arg1	extension					369:377	glycan chain extension	356:377	glycan chain extension	356:377	ST3GAL1 is a sialyltransferase that adds sialic acid to core 1 glycans, thereby terminating glycan chain extension.
33177111	7	45	theme	N-	916:917	arg1	analyses					904:911	Detailed analyses	895:911	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry	895:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	8	46	theme	CD55	1151:1154	arg1	profile					1140:1146	The O-glycan profile	1127:1146	The O-glycan profile of CD55	1127:1154	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	8	47	gly	nonsialylated	1193:1205	arg1	core					1207:1210	nonsialylated core 1	1193:1212	nonsialylated core 1	1193:1212	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	1	48	theme	tumor	251:255	arg1	cells					257:261	tumor cells	251:261	tumor cells	251:261	Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells.
33177111	10	49	theme	checkpoint	1654:1663	arg1	molecule					1665:1672	an immune checkpoint molecule	1644:1672	an immune checkpoint molecule for cancer cells	1644:1689	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	4	50	from	role	510:513	arg1	cancer					536:541	breast cancer	529:541	breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1	529:582	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	6	51	link	N-linked	780:787	arg1	site					803:806	one N-linked glycosylation site	776:806	one N-linked glycosylation site	776:806	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	8	52	gly	monosialylated	1218:1231	arg1	core					1233:1236	monosialylated core 2	1218:1238	monosialylated core 2	1218:1238	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	9	53	theme	cancer	1471:1476	arg1	cells					1478:1482	breast cancer cells	1464:1482	breast cancer cells	1464:1482	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	7	54	theme	ST3GAL1	1108:1114	arg1	silencing					1116:1124	ST3GAL1 silencing	1108:1124	ST3GAL1 silencing	1108:1124	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	5	55	theme	regulatory	691:700	arg1	protein					702:708	an important complement regulatory protein	667:708	an important complement regulatory protein	667:708	CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity.
33177111	5	55	theme	regulatory	691:700	arg1	CD55					659:662	CD55	659:662	CD55	659:662	CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity.
33177111	6	56	theme	N-linked	780:787	arg1	site					803:806	one N-linked glycosylation site	776:806	one N-linked glycosylation site	776:806	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	2	57	theme	sialic	305:310	arg1	acid					312:315	sialic acid	305:315	sialic acid	305:315	ST3GAL1 is a sialyltransferase that adds sialic acid to core 1 glycans, thereby terminating glycan chain extension.
33177111	8	58	theme	core	1275:1278	arg1	structure					1282:1290	the disialylated core 2 structure	1258:1290	the disialylated core 2 structure	1258:1290	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	1	59	theme	glycoproteins	210:222	arg1	function					198:205	the function	194:205	the function of glycoproteins	194:222	Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells.
33177111	4	60	theme	target	631:636	arg1	proteins					638:645	the potential target proteins	617:645	the potential target proteins of ST3GAL1	617:656	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	8	61	gly	disialylated	1262:1273	arg1	structure					1282:1290	the disialylated core 2 structure	1258:1290	the disialylated core 2 structure	1258:1290	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	8	62	theme	ST3GAL1	1298:1304	arg1	silencing					1306:1314	ST3GAL1 silencing	1298:1314	ST3GAL1 silencing	1298:1314	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	5	63	theme	important	670:678	arg1	protein					702:708	an important complement regulatory protein	667:708	an important complement regulatory protein	667:708	CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity.
33177111	5	63	theme	important	670:678	arg1	CD55					659:662	CD55	659:662	CD55	659:662	CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity.
33177111	7	64	theme	tandem	1028:1033	arg1	spectrometry					1040:1051	tandem mass spectrometry	1028:1051	tandem mass spectrometry	1028:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	6	65	gly	O-glycosylated	879:892	arg1	domain					838:843	a Ser/Thr-rich domain	823:843	a Ser/Thr-rich domain	823:843	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	6	65	gly	O-glycosylated	879:892	arg1	O-glycosylated					879:892	O-glycosylated	879:892	O-glycosylated	879:892	CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated.
33177111	10	66	gly	sialylation	1614:1624	arg1	CD55					1629:1632	CD55	1629:1632	CD55	1629:1632	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	7	67	theme	breast	1005:1010	arg1	cells					1019:1023	scramble or ST3GAL1 siRNA-treated breast cancer cells	971:1023	cells	1019:1023	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	1	68	theme	glycosyltransferases	148:167	arg1	expression					119:128	expression	119:128	expression	119:128	Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells.
33177111	1	68	theme	glycosyltransferases	148:167	arg1	activities					134:143	activities	134:143	activities	134:143	Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells.
33177111	4	69	theme	ST3GAL1	518:524	arg1	role					510:513	the role	506:513	the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1	506:582	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	7	70	theme	ST3GAL1	983:989	arg1	cells					1019:1023	scramble or ST3GAL1 siRNA-treated breast cancer cells	971:1023	cells	1019:1023	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	0	71	from	Evasion	50:56	arg1	Cancer					61:66	Cancer	61:66	Cancer	61:66	Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer.
33177111	9	72	gly	desialylation	1352:1364	arg1	CD55					1369:1372	CD55	1369:1372	CD55	1369:1372	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	5	73	theme	complement-mediated	733:751	arg1	cytotoxicity					753:764	complement-mediated cytotoxicity	733:764	complement-mediated cytotoxicity	733:764	CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity.
33177111	7	74	theme	scramble	971:978	arg1	cells					1019:1023	scramble or ST3GAL1 siRNA-treated breast cancer cells	971:1023	cells	1019:1023	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
33177111	9	75	link	O-linked	1343:1350	arg1	desialylation					1352:1364	O-linked desialylation	1343:1364	O-linked desialylation of CD55 by ST3GAL1 silencing	1343:1393	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	9	76	theme	O-linked	1343:1350	arg1	desialylation					1352:1364	O-linked desialylation	1343:1364	O-linked desialylation of CD55 by ST3GAL1 silencing	1343:1393	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	3	77	theme	breast	383:388	arg1	carcinomas					390:399	breast carcinomas	383:399	breast carcinomas	383:399	In breast carcinomas, overexpression of ST3GAL1 promotes tumorigenesis and correlates with increased tumor grade.
33177111	10	78	link	O-linked	1605:1612	arg1	sialylation					1614:1624	ST3GAL1-mediated O-linked sialylation	1588:1624	ST3GAL1-mediated O-linked sialylation of CD55	1588:1632	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	3	79	theme	tumor	481:485	arg1	grade					487:491	increased tumor grade	471:491	increased tumor grade	471:491	In breast carcinomas, overexpression of ST3GAL1 promotes tumorigenesis and correlates with increased tumor grade.
33177111	9	80	theme	antibody-dependent	1512:1529	arg1	cytotoxicity					1545:1556	antibody-dependent cell-mediated cytotoxicity	1512:1556	antibody-dependent cell-mediated cytotoxicity	1512:1556	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	4	81	theme	breast	529:534	arg1	cancer					536:541	breast cancer	529:541	breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1	529:582	In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1.
33177111	10	82	theme	ST3GAL1	1737:1743	arg1	inhibition					1723:1732	inhibition	1723:1732	inhibition of ST3GAL1	1723:1743	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	10	82	theme	ST3GAL1	1737:1743	arg1	strategy					1760:1767	a potential strategy	1748:1767	a potential strategy to block CD55-mediated immune evasion	1748:1805	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	8	83	theme	O-glycan	1131:1138	arg1	profile					1140:1146	The O-glycan profile	1127:1146	The O-glycan profile of CD55	1127:1154	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	10	84	theme	ST3GAL1-mediated	1588:1603	arg1	sialylation					1614:1624	ST3GAL1-mediated O-linked sialylation	1588:1624	ST3GAL1-mediated O-linked sialylation of CD55	1588:1632	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	2	85	theme	core	320:323	arg1	glycans					327:333	core 1 glycans	320:333	core 1 glycans	320:333	ST3GAL1 is a sialyltransferase that adds sialic acid to core 1 glycans, thereby terminating glycan chain extension.
33177111	9	86	theme	C3	1417:1418	arg1	deposition					1420:1429	increased C3 deposition	1407:1429	increased C3 deposition	1407:1429	We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity.
33177111	8	87	theme	structure	1282:1290	arg1	expense					1247:1253	the expense	1243:1253	the expense of the disialylated core 2 structure	1243:1290	The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing.
33177111	10	88	theme	CD55	1629:1632	arg1	sialylation					1614:1624	ST3GAL1-mediated O-linked sialylation	1588:1624	ST3GAL1-mediated O-linked sialylation of CD55	1588:1632	These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.
33177111	2	89	theme	glycan	356:361	arg1	extension					369:377	glycan chain extension	356:377	glycan chain extension	356:377	ST3GAL1 is a sialyltransferase that adds sialic acid to core 1 glycans, thereby terminating glycan chain extension.
33177111	7	90	theme	Detailed	895:902	arg1	analyses					904:911	Detailed analyses	895:911	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry	895:1051	Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing.
32915358	4	0	theme	monoclonal	951:960	arg1	mAbs					974:977	mAbs	974:977	mAbs	974:977	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	4	0	theme	monoclonal	951:960	arg1	antibodies					962:971	monoclonal antibodies	951:971	monoclonal antibodies (mAbs)	951:978	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	5	1	theme	serum	1153:1157	arg1	glycoproteins					1159:1171	single serum glycoproteins	1146:1171	single serum glycoproteins	1146:1171	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	6	2	theme	individual	1533:1542	arg1	diseases					1558:1565	these individual glycosylation diseases	1527:1565	these individual glycosylation diseases	1527:1565	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	1	3	theme	disorders	293:301	arg1	diagnosis					272:280	diagnosis	272:280	diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG)	272:374	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	8	4	theme	sensitive	1809:1817	arg1	approach					1835:1842	a sensitive high throughput approach	1807:1842	a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species	1807:1963	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	1	5	theme	glycan	306:311	arg1	biosynthesis					313:324	glycan biosynthesis	306:324	glycan biosynthesis named congenital disorders of glycosylation (CDG)	306:374	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	4	6	theme	biological	923:932	arg1	interest					934:941	pharmaceutical and biological interest	904:941	interest	934:941	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	4	7	gly	glycoproteins	887:899	arg1	glycoproteins					887:899	glycoproteins	887:899	glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs)	887:978	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	4	7	gly	glycoproteins	887:899	arg1	antibodies					962:971	monoclonal antibodies	951:971	monoclonal antibodies (mAbs)	951:978	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	8	8	theme	throughput	1824:1833	arg1	approach					1835:1842	a sensitive high throughput approach	1807:1842	a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species	1807:1963	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	4	9	theme	most	716:719	arg1	techniques					736:745	most derivatization techniques	716:745	most derivatization techniques	716:745	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	5	10	gly	glycoproteins	1159:1171	arg1	glycoproteins					1159:1171	single serum glycoproteins	1146:1171	single serum glycoproteins	1146:1171	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	5	11	theme	serum	1136:1140	arg1	characterization					1110:1125	a detailed N-glycan characterization	1090:1125	a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1090:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	8	12	theme	N-glycome	1854:1862	arg1	analysis					1864:1871	serum N-glycome analysis	1848:1871	serum N-glycome analysis	1848:1871	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	6	13	theme	Chromatography	1308:1321	arg1	separation					1343:1352	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation	1284:1352	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans	1284:1386	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	5	14	theme	single	1146:1151	arg1	glycoproteins					1159:1171	single serum glycoproteins	1146:1171	single serum glycoproteins	1146:1171	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	1	15	theme	distinctive	241:251	arg1	changes					253:259	distinctive changes	241:259	distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG)	241:374	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	6	16	theme	Hydrophilic	1284:1294	arg1	HILIC					1324:1328	HILIC	1324:1328	HILIC	1324:1328	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	6	16	theme	Hydrophilic	1284:1294	arg1	Chromatography					1308:1321	Hydrophilic Interaction Chromatography	1284:1321	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans	1284:1386	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	5	17	theme	N-glycan	1101:1108	arg1	characterization					1110:1125	a detailed N-glycan characterization	1090:1125	a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1090:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	8	18	theme	valuable	1879:1886	arg1	option					1888:1893	a valuable option	1877:1893	a valuable option for glycan detection and separation particularly for isomeric species	1877:1963	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	4	19	theme	commercial	784:793	arg1	kits					806:809	some commercial analytical kits	779:809	some commercial analytical kits	779:809	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	5	20	with	patients	1187:1194	arg1	CDG					1201:1203	CDG	1201:1203	CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1201:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	6	21	theme	derivatized	1366:1376	arg1	N-glycans					1378:1386	the RFMS derivatized N-glycans	1357:1386	the RFMS derivatized N-glycans	1357:1386	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	6	22	from	knowledge	1495:1503	arg1	profiles					1515:1522	glycan profiles	1508:1522	glycan profiles in these individual glycosylation diseases	1508:1565	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	3	23	theme	functional	670:679	arg1	tag					681:683	a functional tag	668:683	a functional tag prior to LC-MS analysis	668:707	To enhance detection sensitivity, glycans are commonly labelled with a functional tag prior to LC-MS analysis.
32915358	1	24	theme	N-glycan	146:153	arg1	analyses					155:162	N-glycan analyses	146:162	N-glycan analyses	146:162	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	2	25	theme	powerful	521:528	arg1	methods					541:547	powerful analytical methods	521:547	powerful analytical methods for N-glycan identification and characterization	521:596	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	5	26	from	characterization	1110:1125	arg1	patients					1187:1194	specific patients	1178:1194	specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1178:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	1	27	theme	disease-associated	185:202	arg1	biomarkers					204:213	disease-associated biomarkers	185:213	disease-associated biomarkers	185:213	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	2	28	theme	N-glycan	553:560	arg1	identification					562:575	N-glycan identification	553:575	N-glycan identification	553:575	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	0	29	from	HILIC-UPLC-MS	0:12	arg1	Disorders					102:110	Congenital Disorders	91:110	Congenital Disorders	91:110	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	6	30	theme	patients	1433:1440	arg1	details					1422:1428	structural details	1411:1428	structural details of patients serum released N-glycans	1411:1465	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	5	31	theme	glycoproteins	1159:1171	arg1	characterization					1110:1125	a detailed N-glycan characterization	1090:1125	a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1090:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	6	32	dep	patients	1433:1440	arg1	serum					1442:1446	serum	1442:1446	serum	1442:1446	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	5	33	theme	specific	1178:1185	arg1	patients					1187:1194	specific patients	1178:1194	specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1178:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	0	34	theme	isomeric	38:45	arg1	separation					56:65	isomeric N-glycan separation	38:65	isomeric N-glycan separation	38:65	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	2	35	theme	mass	482:485	arg1	MS					501:502	MS	501:502	MS	501:502	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	2	35	theme	mass	482:485	arg1	spectrometry					487:498	electrospray ionization (ESI) - mass spectrometry	450:498	electrospray ionization (ESI) - mass spectrometry (MS)	450:503	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	5	36	from	patients	1187:1194	arg1	glycoproteins					1159:1171	single serum glycoproteins	1146:1171	single serum glycoproteins	1146:1171	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	5	36	from	patients	1187:1194	arg1	characterization					1110:1125	a detailed N-glycan characterization	1090:1125	a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1090:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	5	36	from	patients	1187:1194	arg1	serum					1136:1140	total serum	1130:1140	total serum	1130:1140	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	1	37	theme	biosynthesis	313:324	arg1	disorders					293:301	genetic disorders	285:301	genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG)	285:374	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	5	38	theme	RapiFluor-MS	1025:1036	arg1	capabilities					1009:1020	the analytical capabilities	994:1020	the analytical capabilities of RapiFluor-MS (RFMS)	994:1043	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	0	39	theme	high	18:21	arg1	throughput					23:32	high throughput	18:32	high throughput	18:32	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	1	40	theme	congenital	332:341	arg1	disorders					343:351	congenital disorders	332:351	congenital disorders of glycosylation (CDG)	332:374	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	5	41	dep	CDG	1201:1203	arg1	TMEM199-CDG					1239:1249	TMEM199-CDG	1239:1249	TMEM199-CDG	1239:1249	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	5	41	dep	CDG	1201:1203	arg1	MOGS-CDG					1229:1236	MOGS-CDG	1229:1236	MOGS-CDG	1229:1236	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	5	41	dep	CDG	1201:1203	arg1	ALG12-CDG					1218:1226	ALG12-CDG	1218:1226	ALG12-CDG	1218:1226	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	5	41	dep	CDG	1201:1203	arg1	MAN1B1-CDG					1206:1215	MAN1B1-CDG	1206:1215	MAN1B1-CDG	1206:1215	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	3	42	theme	LC-MS	694:698	arg1	analysis					700:707	LC-MS analysis	694:707	LC-MS analysis	694:707	To enhance detection sensitivity, glycans are commonly labelled with a functional tag prior to LC-MS analysis.
32915358	4	43	theme	glycoproteins	887:899	arg1	N-deglycosylation					843:859	N-deglycosylation	843:859	N-deglycosylation	843:859	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	4	43	theme	glycoproteins	887:899	arg1	labelling					874:882	N-glycan labelling	865:882	N-glycan labelling	865:882	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	2	44	theme	electrospray	450:461	arg1	MS					501:502	MS	501:502	MS	501:502	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	2	44	theme	electrospray	450:461	arg1	spectrometry					487:498	electrospray ionization (ESI) - mass spectrometry	450:498	electrospray ionization (ESI) - mass spectrometry (MS)	450:503	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	6	45	theme	current	1487:1493	arg1	knowledge					1495:1503	the current knowledge	1483:1503	the current knowledge on glycan profiles in these individual glycosylation diseases	1483:1565	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	3	46	theme	prior	685:689	arg1	tag					681:683	a functional tag	668:683	a functional tag prior to LC-MS analysis	668:707	To enhance detection sensitivity, glycans are commonly labelled with a functional tag prior to LC-MS analysis.
32915358	4	47	theme	pharmaceutical	904:917	arg1	interest					934:941	pharmaceutical and biological interest	904:941	interest	934:941	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	0	48	theme	N-glycan	47:54	arg1	separation					56:65	isomeric N-glycan separation	38:65	isomeric N-glycan separation	38:65	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	5	49	theme	detailed	1092:1099	arg1	characterization					1110:1125	a detailed N-glycan characterization	1090:1125	a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG)	1090:1250	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	8	50	theme	RFMS	1753:1756	arg1	method					1758:1763	RFMS method	1753:1763	RFMS method	1753:1763	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	7	51	theme	applied	1572:1578	arg1	methodology					1580:1590	The applied methodology	1568:1590	The applied methodology	1568:1590	The applied methodology enabled to differentiate in some cases either structural isomers and isomers differing in the linkage type.
32915358	5	52	theme	modified	1071:1078	arg1	protocol					1080:1087	a slightly modified protocol	1060:1087	a slightly modified protocol	1060:1087	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	6	53	theme	RFMS	1361:1364	arg1	N-glycans					1378:1386	the RFMS derivatized N-glycans	1357:1386	the RFMS derivatized N-glycans	1357:1386	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	2	54	theme	liquid	397:402	arg1	LC					420:421	LC	420:421	LC	420:421	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	2	54	theme	liquid	397:402	arg1	chromatography					404:417	liquid chromatography	397:417	liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS)	397:503	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	6	55	theme	glycosylation	1544:1556	arg1	diseases					1558:1565	these individual glycosylation diseases	1527:1565	these individual glycosylation diseases	1527:1565	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	1	56	theme	genetic	285:291	arg1	disorders					293:301	genetic disorders	285:301	genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG)	285:374	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	8	57	theme	reported	1713:1720	arg1	applications					1722:1733	All the here reported applications	1700:1733	All the here reported applications	1700:1733	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	6	58	theme	-UPLC-ESI-MS	1330:1341	arg1	separation					1343:1352	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation	1284:1352	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans	1284:1386	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	6	59	theme	released	1448:1455	arg1	N-glycans					1457:1465	released N-glycans	1448:1465	released N-glycans	1448:1465	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	3	60	theme	detection	610:618	arg1	sensitivity					620:630	detection sensitivity	610:630	detection sensitivity	610:630	To enhance detection sensitivity, glycans are commonly labelled with a functional tag prior to LC-MS analysis.
32915358	8	61	theme	high	1819:1822	arg1	approach					1835:1842	a sensitive high throughput approach	1807:1842	a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species	1807:1963	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	4	62	theme	interest	934:941	arg1	glycoproteins					887:899	glycoproteins	887:899	glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs)	887:978	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	4	62	theme	interest	934:941	arg1	antibodies					962:971	monoclonal antibodies	951:971	monoclonal antibodies (mAbs)	951:978	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	6	63	theme	structural	1411:1420	arg1	details					1422:1428	structural details	1411:1428	structural details of patients serum released N-glycans	1411:1465	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	8	64	theme	serum	1848:1852	arg1	analysis					1864:1871	serum N-glycome analysis	1848:1871	serum N-glycome analysis	1848:1871	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	6	65	theme	Interaction	1296:1306	arg1	HILIC					1324:1328	HILIC	1324:1328	HILIC	1324:1328	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	6	65	theme	Interaction	1296:1306	arg1	Chromatography					1308:1321	Hydrophilic Interaction Chromatography	1284:1321	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans	1284:1386	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	6	66	from	profiles	1515:1522	arg1	diseases					1558:1565	these individual glycosylation diseases	1527:1565	these individual glycosylation diseases	1527:1565	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	6	67	theme	N-glycans	1378:1386	arg1	separation					1343:1352	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation	1284:1352	Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans	1284:1386	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	5	68	theme	analytical	998:1007	arg1	capabilities					1009:1020	the analytical capabilities	994:1020	the analytical capabilities of RapiFluor-MS (RFMS)	994:1043	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	7	69	theme	linkage	1686:1692	arg1	type					1694:1697	the linkage type	1682:1697	the linkage type	1682:1697	The applied methodology enabled to differentiate in some cases either structural isomers and isomers differing in the linkage type.
32915358	5	70	theme	total	1130:1134	arg1	serum					1136:1140	total serum	1130:1140	total serum	1130:1140	We exploited the analytical capabilities of RapiFluor-MS (RFMS) to perform, by a slightly modified protocol, a detailed N-glycan characterization of total serum and single serum glycoproteins from specific patients with CDG (MAN1B1-CDG, ALG12-CDG, MOGS-CDG, TMEM199-CDG).
32915358	4	71	theme	derivatization	721:734	arg1	techniques					736:745	most derivatization techniques	716:745	most derivatization techniques	716:745	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	0	72	theme	Congenital	91:100	arg1	Disorders					102:110	Congenital Disorders	91:110	Congenital Disorders	91:110	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	8	73	theme	glycan	1899:1904	arg1	detection					1906:1914	glycan detection	1899:1914	glycan detection	1899:1914	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	0	74	theme	human	130:134	arg1	diseases					136:143	human diseases	130:143	human diseases	130:143	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	2	75	theme	analytical	530:539	arg1	methods					541:547	powerful analytical methods	521:547	powerful analytical methods for N-glycan identification and characterization	521:596	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	8	76	theme	isomeric	1948:1955	arg1	species					1957:1963	isomeric species	1948:1963	isomeric species	1948:1963	All the here reported applications demonstrated that RFMS method, coupled to HILIC-UPLC-ESI-MS, represents a sensitive high throughput approach for serum N-glycome analysis and a valuable option for glycan detection and separation particularly for isomeric species.
32915358	4	77	theme	analytical	795:804	arg1	kits					806:809	some commercial analytical kits	779:809	some commercial analytical kits	779:809	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	6	78	theme	glycan	1508:1513	arg1	profiles					1515:1522	glycan profiles	1508:1522	glycan profiles in these individual glycosylation diseases	1508:1565	This strategy, accomplished by Hydrophilic Interaction Chromatography (HILIC)-UPLC-ESI-MS separation of the RFMS derivatized N-glycans, allowed us to uncover structural details of patients serum released N-glycans, thus extending the current knowledge on glycan profiles in these individual glycosylation diseases.
32915358	2	79	theme	ESI	475:477	arg1	MS					501:502	MS	501:502	MS	501:502	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	2	79	theme	ESI	475:477	arg1	spectrometry					487:498	electrospray ionization (ESI) - mass spectrometry	450:498	electrospray ionization (ESI) - mass spectrometry (MS)	450:503	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	2	80	theme	ionization	463:472	arg1	MS					501:502	MS	501:502	MS	501:502	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	2	80	theme	ionization	463:472	arg1	spectrometry					487:498	electrospray ionization (ESI) - mass spectrometry	450:498	electrospray ionization (ESI) - mass spectrometry (MS)	450:503	Strategies based on liquid chromatography (LC) preferentially coupled to electrospray ionization (ESI) - mass spectrometry (MS) have emerged as powerful analytical methods for N-glycan identification and characterization.
32915358	4	81	gly	N-deglycosylation	843:859	arg1	glycoproteins					887:899	glycoproteins	887:899	glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs)	887:978	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	4	81	gly	N-deglycosylation	843:859	arg1	antibodies					962:971	monoclonal antibodies	951:971	monoclonal antibodies (mAbs)	951:978	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
32915358	7	82	theme	structural	1638:1647	arg1	isomers					1649:1655	structural isomers	1638:1655	structural isomers	1638:1655	The applied methodology enabled to differentiate in some cases either structural isomers and isomers differing in the linkage type.
32915358	1	83	theme	glycosylation	356:368	arg1	disorders					343:351	congenital disorders	332:351	congenital disorders of glycosylation (CDG)	332:374	N-glycan analyses may serve uncovering disease-associated biomarkers, as well as for profiling distinctive changes supporting diagnosis of genetic disorders of glycan biosynthesis named congenital disorders of glycosylation (CDG).
32915358	0	84	dep	HILIC-UPLC-MS	0:12	arg1	Glycosylation					112:124	Glycosylation	112:124	Glycosylation	112:124	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	0	84	dep	HILIC-UPLC-MS	0:12	arg1	diseases					136:143	human diseases	130:143	human diseases	130:143	HILIC-UPLC-MS for high throughput and isomeric N-glycan separation and characterization in Congenital Disorders Glycosylation and human diseases.
32915358	4	85	theme	N-glycan	865:872	arg1	labelling					874:882	N-glycan labelling	865:882	N-glycan labelling	865:882	Since most derivatization techniques are notoriously time-consuming, some commercial analytical kits have been developed to speed up N-deglycosylation and N-glycan labelling of glycoproteins of pharmaceutical and biological interest such as monoclonal antibodies (mAbs).
31837192	9	0	from	amounts	1598:1604	arg1	glycoproteins					1674:1686	several plant-produced glycoproteins	1651:1686	several plant-produced glycoproteins	1651:1686	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	3	1	with	hard	589:592	arg1	exception					502:510	exception	502:510	exception of monoclonal antibodies	502:535	However, with exception of monoclonal antibodies, homogenous human-like β1,4-galactosylation is very hard to achieve in recombinant glycoproteins.
31837192	10	2	theme	complex	1758:1764	arg1	N-glycans					1766:1774	galactosylated complex N-glycans	1743:1774	galactosylated complex N-glycans of plant-produced glycoproteins	1743:1806	Altogether, our data demonstrate that NbBGAL1 acts on galactosylated complex N-glycans of plant-produced glycoproteins.
31837192	7	3	theme	NbBGAL1	1239:1245	arg1	localization					1259:1270	the NbBGAL1 subcellular localization	1235:1270	the NbBGAL1 subcellular localization	1235:1270	Here, we determined the NbBGAL1 subcellular localization, substrate specificity and in planta biological activity.
31837192	1	4	theme	proteins	109:116	arg1	Glyco-design					93:104	Glyco-design	93:104	Glyco-design of proteins	93:116	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	1	4	theme	proteins	109:116	arg1	tool					132:135	a powerful tool	121:135	a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins	121:271	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	8	5	theme	β1,3-galactose	1372:1385	arg1	residues					1387:1394	β1,4- and β1,3-galactose residues	1362:1394	β1,4- and β1,3-galactose residues on both N- and O-glycans	1362:1419	We show that NbBGAL1 can remove β1,4- and β1,3-galactose residues on both N- and O-glycans.
31837192	3	6	theme	recombinant	608:618	arg1	glycoproteins					620:632	recombinant glycoproteins	608:632	recombinant glycoproteins	608:632	However, with exception of monoclonal antibodies, homogenous human-like β1,4-galactosylation is very hard to achieve in recombinant glycoproteins.
31837192	1	7	theme	structure-function	163:180	arg1	relationship					182:193	structure-function relationship	163:193	structure-function relationship	163:193	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	6	8	theme	uncharacterized	1019:1033	arg1	mechanisms					1035:1044	the so far uncharacterized mechanisms	1008:1044	the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins	1008:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	4	9	theme	heterogeneous	804:816	arg1	galactosylation					827:841	heterogeneous terminal galactosylation	804:841	heterogeneous terminal galactosylation	804:841	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	10	10	theme	glycoproteins	1794:1806	arg1	N-glycans					1766:1774	galactosylated complex N-glycans	1743:1774	galactosylated complex N-glycans of plant-produced glycoproteins	1743:1806	Altogether, our data demonstrate that NbBGAL1 acts on galactosylated complex N-glycans of plant-produced glycoproteins.
31837192	6	11	from	apoplast	1195:1202	arg1	active					1181:1186	active	1181:1186	active	1181:1186	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	6	12	theme	proteins	1126:1133	arg1	glycans					1106:1112	glycans	1106:1112	glycans of secreted proteins	1106:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	2	13	from	advances	388:395	arg1	glyco-engineering					400:416	glyco-engineering	400:416	glyco-engineering	400:416	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	5	14	theme	obvious	853:859	arg1	β-galactosidases					929:944	β-galactosidases	929:944	β-galactosidases (BGALs) from the glycosyl hydrolase family GH35	929:992	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	5	14	theme	obvious	853:859	arg1	suspects					861:868	The most obvious suspects	844:868	The most obvious suspects to be involved in trimming terminal galactose residues	844:923	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	1	15	theme	obtaining	202:210	arg1	profiles					212:219	obtaining profiles	202:219	obtaining profiles optimized for efficacy of therapeutic glycoproteins	202:271	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	4	16	theme	incomplete	768:777	arg1	N-glycans					789:797	incomplete processed N-glycans	768:797	incomplete processed N-glycans	768:797	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	8	17	theme	β1,4-	1362:1366	arg1	residues					1387:1394	β1,4- and β1,3-galactose residues	1362:1394	β1,4- and β1,3-galactose residues on both N- and O-glycans	1362:1419	We show that NbBGAL1 can remove β1,4- and β1,3-galactose residues on both N- and O-glycans.
31837192	5	18	from	family	982:987	arg1	BGALs					947:951	BGALs	947:951	BGALs	947:951	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	5	18	from	family	982:987	arg1	β-galactosidases					929:944	β-galactosidases	929:944	β-galactosidases (BGALs) from the glycosyl hydrolase family GH35	929:992	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	5	18	from	family	982:987	arg1	suspects					861:868	The most obvious suspects	844:868	The most obvious suspects to be involved in trimming terminal galactose residues	844:923	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	9	19	theme	plant-produced	1659:1672	arg1	glycoproteins					1674:1686	several plant-produced glycoproteins	1651:1686	several plant-produced glycoproteins	1651:1686	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	6	20	theme	galactose	1082:1090	arg1	residues					1092:1099	terminal galactose residues	1073:1099	terminal galactose residues from glycans of secreted proteins	1073:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	1	21	theme	powerful	123:130	arg1	Glyco-design					93:104	Glyco-design	93:104	Glyco-design of proteins	93:116	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	1	21	theme	powerful	123:130	arg1	tool					132:135	a powerful tool	121:135	a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins	121:271	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	5	22	dep	suspects	861:868	arg1	involved					876:883	involved	876:883	to be involved in trimming terminal galactose residues	870:923	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	5	23	theme	galactose	906:914	arg1	residues					916:923	trimming terminal galactose residues	888:923	trimming terminal galactose residues	888:923	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	2	24	gly	glycoproteins	473:485	arg1	glycoproteins					473:485	plant-derived glycoproteins	459:485	plant-derived glycoproteins	459:485	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	0	25	theme	O-glycans	64:72	arg1	β-galactosylation					36:52	β-galactosylation	36:52	β-galactosylation of N- and O-glycans	36:72	BGAL1 depletion boosts the level of β-galactosylation of N- and O-glycans in N. benthamiana.
31837192	9	26	theme	BGAL1	1432:1436	arg1	down-regulation					1438:1452	Transient BGAL1 down-regulation	1422:1452	Transient BGAL1 down-regulation by RNA interference (RNAi)	1422:1479	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	9	27	gly	glycoproteins	1674:1686	arg1	glycoproteins					1674:1686	several plant-produced glycoproteins	1651:1686	several plant-produced glycoproteins	1651:1686	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	1	28	from	tool	132:135	arg1	profiles					212:219	obtaining profiles	202:219	obtaining profiles optimized for efficacy of therapeutic glycoproteins	202:271	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	1	28	from	tool	132:135	arg1	studies					152:158	fundamental studies	140:158	fundamental studies of structure-function relationship	140:193	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	5	29	theme	trimming	888:895	arg1	residues					916:923	trimming terminal galactose residues	888:923	trimming terminal galactose residues	888:923	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	7	30	from	activity	1320:1327	arg1	planta					1302:1307	planta	1302:1307	planta	1302:1307	Here, we determined the NbBGAL1 subcellular localization, substrate specificity and in planta biological activity.
31837192	0	31	theme	BGAL1	0:4	arg1	depletion					6:14	BGAL1 depletion	0:14	BGAL1 depletion	0:14	BGAL1 depletion boosts the level of β-galactosylation of N- and O-glycans in N. benthamiana.
31837192	3	32	theme	antibodies	526:535	arg1	exception					502:510	exception	502:510	exception of monoclonal antibodies	502:535	However, with exception of monoclonal antibodies, homogenous human-like β1,4-galactosylation is very hard to achieve in recombinant glycoproteins.
31837192	5	33	theme	hydrolase	972:980	arg1	family					982:987	the glycosyl hydrolase family GH35	959:992	the glycosyl hydrolase family GH35	959:992	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	4	34	link	plant-derived	726:738	arg1	glycoproteins					740:752	many plant-derived glycoproteins	721:752	many plant-derived glycoproteins	721:752	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	2	35	theme	plant-derived	459:471	arg1	glycoproteins					473:485	plant-derived glycoproteins	459:485	plant-derived glycoproteins	459:485	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	2	36	gly	glycoproteins	362:374	arg1	glycoproteins					362:374	recombinant glycoproteins	350:374	recombinant glycoproteins	350:374	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	0	37	theme	N-	57:58	arg1	β-galactosylation					36:52	β-galactosylation	36:52	β-galactosylation of N- and O-glycans	36:72	BGAL1 depletion boosts the level of β-galactosylation of N- and O-glycans in N. benthamiana.
31837192	7	38	theme	substrate	1273:1281	arg1	specificity					1283:1293	substrate specificity	1273:1293	substrate specificity	1273:1293	Here, we determined the NbBGAL1 subcellular localization, substrate specificity and in planta biological activity.
31837192	9	39	theme	genome	1504:1509	arg1	editing					1511:1517	genome editing	1504:1517	genome editing	1504:1517	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	9	40	from	activity	1554:1561	arg1	N. benthamiana					1566:1579	N. benthamiana	1566:1579	N. benthamiana	1566:1579	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	7	41	from	localization	1259:1270	arg1	planta					1302:1307	planta	1302:1307	planta	1302:1307	Here, we determined the NbBGAL1 subcellular localization, substrate specificity and in planta biological activity.
31837192	6	42	from	glycans	1106:1112	arg1	trimming					1061:1068	the trimming	1057:1068	the trimming of terminal galactose residues from glycans of secreted proteins	1057:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	6	42	from	glycans	1106:1112	arg1	residues					1092:1099	terminal galactose residues	1073:1099	terminal galactose residues from glycans of secreted proteins	1073:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	2	43	theme	recombinant	350:360	arg1	glycoproteins					362:374	recombinant glycoproteins	350:374	recombinant glycoproteins	350:374	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	3	44	gly	glycoproteins	620:632	arg1	glycoproteins					620:632	recombinant glycoproteins	608:632	recombinant glycoproteins	608:632	However, with exception of monoclonal antibodies, homogenous human-like β1,4-galactosylation is very hard to achieve in recombinant glycoproteins.
31837192	4	45	theme	β1,4-galactosyltransferase	693:718	arg1	expression					679:688	the expression	675:688	the expression of β1,4-galactosyltransferase	675:718	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	6	46	from	trimming	1061:1068	arg1	glycans					1106:1112	glycans	1106:1112	glycans of secreted proteins	1106:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	9	47	theme	β-galactosidase	1538:1552	arg1	activity					1554:1561	β-galactosidase activity	1538:1561	β-galactosidase activity in N. benthamiana	1538:1579	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	6	48	theme	terminal	1073:1080	arg1	residues					1092:1099	terminal galactose residues	1073:1099	terminal galactose residues from glycans of secreted proteins	1073:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	4	49	theme	many	721:724	arg1	glycoproteins					740:752	many plant-derived glycoproteins	721:752	many plant-derived glycoproteins	721:752	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	7	50	theme	subcellular	1247:1257	arg1	localization					1259:1270	the NbBGAL1 subcellular localization	1235:1270	the NbBGAL1 subcellular localization	1235:1270	Here, we determined the NbBGAL1 subcellular localization, substrate specificity and in planta biological activity.
31837192	2	51	theme	recent	381:386	arg1	advances					388:395	recent advances	381:395	recent advances in glyco-engineering	381:416	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	1	52	theme	glycoproteins	259:271	arg1	efficacy					235:242	efficacy	235:242	efficacy of therapeutic glycoproteins	235:271	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	10	53	theme	galactosylated	1743:1756	arg1	N-glycans					1766:1774	galactosylated complex N-glycans	1743:1774	galactosylated complex N-glycans of plant-produced glycoproteins	1743:1806	Altogether, our data demonstrate that NbBGAL1 acts on galactosylated complex N-glycans of plant-produced glycoproteins.
31837192	4	54	gly	glycoproteins	740:752	arg1	glycoproteins					740:752	many plant-derived glycoproteins	721:752	many plant-derived glycoproteins	721:752	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	2	55	theme	Nicotiana	295:303	arg1	benthamiana					305:315	Nicotiana benthamiana	295:315	particularly Nicotiana benthamiana	282:315	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	2	55	theme	Nicotiana	295:303	arg1	Plants					274:279	Plants	274:279	Plants	274:279	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	0	56	theme	β-galactosylation	36:52	arg1	level					27:31	the level	23:31	the level of β-galactosylation of N- and O-glycans	23:72	BGAL1 depletion boosts the level of β-galactosylation of N- and O-glycans in N. benthamiana.
31837192	4	57	theme	processed	779:787	arg1	N-glycans					789:797	incomplete processed N-glycans	768:797	incomplete processed N-glycans	768:797	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	6	58	from	active	1181:1186	arg1	NbBGAL1					1205:1211	NbBGAL1	1205:1211	NbBGAL1	1205:1211	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	6	58	from	active	1181:1186	arg1	apoplast					1195:1202	the apoplast	1191:1202	the apoplast (NbBGAL1)	1191:1212	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	1	59	theme	relationship	182:193	arg1	studies					152:158	fundamental studies	140:158	fundamental studies of structure-function relationship	140:193	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	10	60	theme	plant-produced	1779:1792	arg1	glycoproteins					1794:1806	plant-produced glycoproteins	1779:1806	plant-produced glycoproteins	1779:1806	Altogether, our data demonstrate that NbBGAL1 acts on galactosylated complex N-glycans of plant-produced glycoproteins.
31837192	5	61	theme	most	848:851	arg1	β-galactosidases					929:944	β-galactosidases	929:944	β-galactosidases (BGALs) from the glycosyl hydrolase family GH35	929:992	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	5	61	theme	most	848:851	arg1	suspects					861:868	The most obvious suspects	844:868	The most obvious suspects to be involved in trimming terminal galactose residues	844:923	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	2	62	theme	attractive	322:331	arg1	Plants					274:279	Plants	274:279	Plants	274:279	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	2	62	theme	attractive	322:331	arg1	hosts					333:337	attractive hosts	322:337	attractive hosts	322:337	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	9	63	theme	galactosylated	1615:1628	arg1	N-glycans					1638:1646	fully galactosylated complex N-glycans	1609:1646	fully galactosylated complex N-glycans	1609:1646	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	6	64	theme	secreted	1117:1124	arg1	proteins					1126:1133	secreted proteins	1117:1133	secreted proteins	1117:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	9	65	theme	N-glycans	1638:1646	arg1	N-glycans					1638:1646	fully galactosylated complex N-glycans	1609:1646	fully galactosylated complex N-glycans	1609:1646	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	9	65	theme	N-glycans	1638:1646	arg1	amounts					1598:1604	the amounts	1594:1604	the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins	1594:1686	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	8	66	from	residues	1387:1394	arg1	N-					1404:1405	N-	1404:1405	N-	1404:1405	We show that NbBGAL1 can remove β1,4- and β1,3-galactose residues on both N- and O-glycans.
31837192	8	66	from	residues	1387:1394	arg1	O-glycans					1411:1419	O-glycans	1411:1419	O-glycans	1411:1419	We show that NbBGAL1 can remove β1,4- and β1,3-galactose residues on both N- and O-glycans.
31837192	9	67	theme	several	1651:1657	arg1	glycoproteins					1674:1686	several plant-produced glycoproteins	1651:1686	several plant-produced glycoproteins	1651:1686	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	6	68	theme	residues	1092:1099	arg1	trimming					1061:1068	the trimming	1057:1068	the trimming of terminal galactose residues from glycans of secreted proteins	1057:1133	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	3	69	theme	homogenous	538:547	arg1	β1,4-galactosylation					560:579	homogenous human-like β1,4-galactosylation	538:579	homogenous human-like β1,4-galactosylation	538:579	However, with exception of monoclonal antibodies, homogenous human-like β1,4-galactosylation is very hard to achieve in recombinant glycoproteins.
31837192	5	70	theme	terminal	897:904	arg1	residues					916:923	trimming terminal galactose residues	888:923	trimming terminal galactose residues	888:923	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	4	71	theme	terminal	818:825	arg1	galactosylation					827:841	heterogeneous terminal galactosylation	804:841	heterogeneous terminal galactosylation	804:841	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	9	72	theme	Transient	1422:1430	arg1	down-regulation					1438:1452	Transient BGAL1 down-regulation	1422:1452	Transient BGAL1 down-regulation by RNA interference (RNAi)	1422:1479	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	1	73	theme	fundamental	140:150	arg1	studies					152:158	fundamental studies	140:158	fundamental studies of structure-function relationship	140:193	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	6	74	theme	N. benthamiana	1149:1162	arg1	BGAL					1164:1167	a N. benthamiana BGAL	1147:1167	a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1)	1147:1212	To elucidate the so far uncharacterized mechanisms leading to the trimming of terminal galactose residues from glycans of secreted proteins, we studied a N. benthamiana BGAL known to be active in the apoplast (NbBGAL1).
31837192	7	75	from	specificity	1283:1293	arg1	planta					1302:1307	planta	1302:1307	planta	1302:1307	Here, we determined the NbBGAL1 subcellular localization, substrate specificity and in planta biological activity.
31837192	4	76	dep	efforts	655:661	arg1	optimize					666:673	optimize	666:673	to optimize the expression of β1,4-galactosyltransferase	663:718	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	9	77	theme	complex	1630:1636	arg1	N-glycans					1638:1646	fully galactosylated complex N-glycans	1609:1646	fully galactosylated complex N-glycans	1609:1646	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	2	78	gly	N-glycosylation	440:454	arg1	glycoproteins					473:485	plant-derived glycoproteins	459:485	plant-derived glycoproteins	459:485	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	10	79	gly	glycoproteins	1794:1806	arg1	glycoproteins					1794:1806	plant-produced glycoproteins	1779:1806	plant-produced glycoproteins	1779:1806	Altogether, our data demonstrate that NbBGAL1 acts on galactosylated complex N-glycans of plant-produced glycoproteins.
31837192	2	80	theme	customized	429:438	arg1	N-glycosylation					440:454	customized N-glycosylation	429:454	customized N-glycosylation of plant-derived glycoproteins	429:485	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	7	81	theme	biological	1309:1318	arg1	activity					1320:1327	biological activity	1309:1327	in planta biological activity	1299:1327	Here, we determined the NbBGAL1 subcellular localization, substrate specificity and in planta biological activity.
31837192	1	82	gly	glycoproteins	259:271	arg1	glycoproteins					259:271	therapeutic glycoproteins	247:271	therapeutic glycoproteins	247:271	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
31837192	9	83	theme	RNA	1457:1459	arg1	RNAi					1475:1478	RNAi	1475:1478	RNAi	1475:1478	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	9	83	theme	RNA	1457:1459	arg1	interference					1461:1472	RNA interference	1457:1472	RNA interference (RNAi)	1457:1479	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	4	84	theme	significant	643:653	arg1	efforts					655:661	significant efforts	643:661	significant efforts to optimize the expression of β1,4-galactosyltransferase	643:718	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	5	85	theme	glycosyl	963:970	arg1	family					982:987	the glycosyl hydrolase family GH35	959:992	the glycosyl hydrolase family GH35	959:992	The most obvious suspects to be involved in trimming terminal galactose residues are β-galactosidases (BGALs) from the glycosyl hydrolase family GH35.
31837192	2	86	theme	glycoproteins	473:485	arg1	N-glycosylation					440:454	customized N-glycosylation	429:454	customized N-glycosylation of plant-derived glycoproteins	429:485	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	9	87	theme	BGAL1	1485:1489	arg1	depletion					1491:1499	BGAL1 depletion	1485:1499	BGAL1 depletion by genome editing	1485:1517	Transient BGAL1 down-regulation by RNA interference (RNAi) and BGAL1 depletion by genome editing drastically reduce β-galactosidase activity in N. benthamiana and increase the amounts of fully galactosylated complex N-glycans on several plant-produced glycoproteins.
31837192	3	88	theme	monoclonal	515:524	arg1	antibodies					526:535	monoclonal antibodies	515:535	monoclonal antibodies	515:535	However, with exception of monoclonal antibodies, homogenous human-like β1,4-galactosylation is very hard to achieve in recombinant glycoproteins.
31837192	2	89	link	plant-derived	459:471	arg1	glycoproteins					473:485	plant-derived glycoproteins	459:485	plant-derived glycoproteins	459:485	Plants, particularly Nicotiana benthamiana, are attractive hosts to produce recombinant glycoproteins, and recent advances in glyco-engineering facilitate customized N-glycosylation of plant-derived glycoproteins.
31837192	3	90	theme	human-like	549:558	arg1	β1,4-galactosylation					560:579	homogenous human-like β1,4-galactosylation	538:579	homogenous human-like β1,4-galactosylation	538:579	However, with exception of monoclonal antibodies, homogenous human-like β1,4-galactosylation is very hard to achieve in recombinant glycoproteins.
31837192	4	91	theme	plant-derived	726:738	arg1	glycoproteins					740:752	many plant-derived glycoproteins	721:752	many plant-derived glycoproteins	721:752	Despite significant efforts to optimize the expression of β1,4-galactosyltransferase, many plant-derived glycoproteins still exhibit incomplete processed N-glycans with heterogeneous terminal galactosylation.
31837192	1	92	theme	therapeutic	247:257	arg1	glycoproteins					259:271	therapeutic glycoproteins	247:271	therapeutic glycoproteins	247:271	Glyco-design of proteins is a powerful tool in fundamental studies of structure-function relationship and in obtaining profiles optimized for efficacy of therapeutic glycoproteins.
32452486	3	0	theme	glycan	311:316	arg1	analysis					329:336	glycan structural analysis	311:336	glycan structural analysis	311:336	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	1	from	enrichment	398:407	arg1	glycans					372:378	glycans	372:378	glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	372:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	1	from	enrichment	398:407	arg1	isolation					359:367	the isolation	355:367	the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	355:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	2	gly	glycopeptides	412:424	arg2	glycopeptides					412:424	glycopeptides	412:424	glycopeptides	412:424	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	1	3	theme	disease	140:146	arg1	states					148:153	many disease states	135:153	many disease states in which glycans play an essential role	135:193	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	3	4	theme	structural	318:327	arg1	analysis					329:336	glycan structural analysis	311:336	glycan structural analysis	311:336	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	4	5	theme	germ	774:777	arg1	WGA					763:765	glycan-binding WGA	748:765	glycan-binding WGA (wheat germ agglutinin) lectin	748:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	5	theme	germ	774:777	arg1	agglutinin					779:788	wheat germ agglutinin	768:788	wheat germ agglutinin	768:788	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	6	theme	lectin-SERS	804:814	arg1	assay					816:820	a lectin-SERS assay	802:820	a lectin-SERS assay	802:820	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	6	7	from	profiles	1024:1031	arg1	lines					1069:1073	two human colorectal cancer cell lines	1036:1073	two human colorectal cancer cell lines	1036:1073	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	3	8	theme	sample	506:511	arg1	sample					506:511	sample	506:511	sample	506:511	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	8	theme	sample	506:511	arg1	amounts					495:501	relatively large amounts	478:501	relatively large amounts of sample	478:511	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	4	9	theme	surface-enhanced	696:711	arg1	SERS					731:734	SERS	731:734	SERS	731:734	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	9	theme	surface-enhanced	696:711	arg1	scattering					719:728	surface-enhanced Raman scattering	696:728	surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin	696:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	7	10	theme	in	1243:1244	arg1	monitoring					1251:1260	the real-time and in situ monitoring	1225:1260	the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids	1225:1323	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	6	11	theme	cell	1064:1067	arg1	lines					1069:1073	two human colorectal cancer cell lines	1036:1073	two human colorectal cancer cell lines	1036:1073	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	6	12	theme	unique	1101:1106	arg1	signatures					1115:1124	different and unique glycan signatures	1087:1124	signatures	1115:1124	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	4	13	theme	Raman	713:717	arg1	SERS					731:734	SERS	731:734	SERS	731:734	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	13	theme	Raman	713:717	arg1	scattering					719:728	surface-enhanced Raman scattering	696:728	surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin	696:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	3	14	theme	non-specialist	543:556	arg1	laboratories					558:569	non-specialist laboratories	543:569	non-specialist laboratories	543:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	7	15	theme	body	1313:1316	arg1	fluids					1318:1323	body fluids	1313:1323	body fluids	1313:1323	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	7	16	theme	tissue	1300:1305	arg1	surface					1280:1286	the surface	1276:1286	the surface of cells or tissue	1276:1305	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	7	17	theme	cells	1291:1295	arg1	surface					1280:1286	the surface	1276:1286	the surface of cells or tissue	1276:1305	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	6	18	theme	surface	1009:1015	arg1	profiles					1024:1031	the surface glycan profiles	1005:1031	the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines	1005:1158	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	3	19	theme	large	489:493	arg1	sample					506:511	sample	506:511	sample	506:511	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	19	theme	large	489:493	arg1	amounts					495:501	relatively large amounts	478:501	relatively large amounts of sample	478:511	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	20	used	used	535:538	arg2	spectrometry					449:460	mass spectrometry	444:460	mass spectrometry	444:460	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	7	21	used	used	1216:1219	arg2	method					1188:1193	this method	1183:1193	this method	1183:1193	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	7	22	dep	in	1243:1244	arg1	situ					1246:1249	situ	1246:1249	situ	1246:1249	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	3	23	from	proteins	385:392	arg1	glycans					372:378	glycans	372:378	glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	372:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	23	from	proteins	385:392	arg1	isolation					359:367	the isolation	355:367	the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	355:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	6	24	theme	cell	1149:1152	arg1	lines					1154:1158	the target cell lines	1138:1158	the target cell lines	1138:1158	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	5	25	theme	solution	860:867	arg1	drop					832:835	one drop	828:835	one drop (1 μL) of glycoprotein solution	828:867	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	5	25	theme	solution	860:867	arg1	μL					840:841	1 μL	838:841	1 μL	838:841	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	6	26	theme	cancer	1057:1062	arg1	lines					1069:1073	two human colorectal cancer cell lines	1036:1073	two human colorectal cancer cell lines	1036:1073	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	6	27	theme	target	1142:1147	arg1	lines					1154:1158	the target cell lines	1138:1158	the target cell lines	1138:1158	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	1	28	theme	important	79:87	arg1	part					89:92	an important part	76:92	an important part of cell signalling that is implicated in many disease states in which glycans play an essential role	76:193	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	1	28	theme	important	79:87	arg1	Glycosylation					59:71	Glycosylation	59:71	Glycosylation	59:71	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	4	29	from	glycans	634:640	arg1	protein					647:653	a protein	645:653	a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin	645:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	0	30	theme	Rapid	0:4	arg1	targeting					27:35	Rapid and sensitive glycan targeting	0:35	Rapid and sensitive glycan targeting	0:35	Rapid and sensitive glycan targeting by lectin-SERS assay.
32452486	6	31	theme	colorectal	1046:1055	arg1	lines					1069:1073	two human colorectal cancer cell lines	1036:1073	two human colorectal cancer cell lines	1036:1073	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	0	32	theme	glycan	20:25	arg1	targeting					27:35	Rapid and sensitive glycan targeting	0:35	Rapid and sensitive glycan targeting	0:35	Rapid and sensitive glycan targeting by lectin-SERS assay.
32452486	6	33	theme	glycan	1108:1113	arg1	signatures					1115:1124	different and unique glycan signatures	1087:1124	signatures	1115:1124	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	6	34	theme	human	1040:1044	arg1	lines					1069:1073	two human colorectal cancer cell lines	1036:1073	two human colorectal cancer cell lines	1036:1073	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	2	35	from	differentiation	226:240	arg1	proteins					256:263	proteins	256:263	proteins	256:263	Therefore rapid and sensitive differentiation of glycans on proteins is highly desirable.
32452486	0	36	theme	sensitive	10:18	arg1	targeting					27:35	Rapid and sensitive glycan targeting	0:35	Rapid and sensitive glycan targeting	0:35	Rapid and sensitive glycan targeting by lectin-SERS assay.
32452486	4	37	with	protein	647:653	arg1	IgG					661:663	IgG	661:663	IgG	661:663	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	1	38	theme	cell	97:100	arg1	signalling					102:111	cell signalling	97:111	cell signalling	97:111	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	7	39	from	monitoring	1251:1260	arg1	fluids					1318:1323	body fluids	1313:1323	body fluids	1313:1323	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	7	39	from	monitoring	1251:1260	arg1	surface					1280:1286	the surface	1276:1286	the surface of cells or tissue	1276:1305	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	1	40	theme	essential	180:188	arg1	role					190:193	an essential role	177:193	an essential role	177:193	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	5	41	theme	ng	916:917	arg1	IgG					919:921	as low as 10 ng IgG	903:921	as low as 10 ng IgG	903:921	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	4	42	gly	glycoprotein	676:687	arg1	glycoprotein					676:687	a model glycoprotein	668:687	a model glycoprotein	668:687	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	2	43	theme	sensitive	216:224	arg1	differentiation					226:240	rapid and sensitive differentiation	206:240	rapid and sensitive differentiation of glycans on proteins	206:263	Therefore rapid and sensitive differentiation of glycans on proteins is highly desirable.
32452486	2	44	from	glycans	245:251	arg1	proteins					256:263	proteins	256:263	proteins	256:263	Therefore rapid and sensitive differentiation of glycans on proteins is highly desirable.
32452486	3	45	theme	mass	444:447	arg1	spectrometry					449:460	mass spectrometry	444:460	mass spectrometry	444:460	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	46	theme	glycopeptides	412:424	arg1	proteins					385:392	proteins	385:392	proteins	385:392	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	46	theme	glycopeptides	412:424	arg1	enrichment					398:407	enrichment	398:407	enrichment of glycopeptides	398:424	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	46	theme	glycopeptides	412:424	arg1	detection					431:439	detection	431:439	detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	431:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	7	47	theme	glycans	1265:1271	arg1	monitoring					1251:1260	the real-time and in situ monitoring	1225:1260	the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids	1225:1323	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	3	48	from	isolation	359:367	arg1	detection					431:439	detection	431:439	detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	431:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	48	from	isolation	359:367	arg1	enrichment					398:407	enrichment	398:407	enrichment of glycopeptides	398:424	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	48	from	isolation	359:367	arg1	proteins					385:392	proteins	385:392	proteins	385:392	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	49	theme	glycans	372:378	arg1	isolation					359:367	the isolation	355:367	the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	355:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	5	50	gly	glycoprotein	847:858	arg1	glycoprotein					847:858	glycoprotein solution	847:867	glycoprotein solution	847:867	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	2	51	theme	rapid	206:210	arg1	differentiation					226:240	rapid and sensitive differentiation	206:240	rapid and sensitive differentiation of glycans on proteins	206:263	Therefore rapid and sensitive differentiation of glycans on proteins is highly desirable.
32452486	1	52	theme	signalling	102:111	arg1	part					89:92	an important part	76:92	an important part of cell signalling that is implicated in many disease states in which glycans play an essential role	76:193	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	1	52	theme	signalling	102:111	arg1	Glycosylation					59:71	Glycosylation	59:71	Glycosylation	59:71	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	0	53	theme	lectin-SERS	40:50	arg1	assay					52:56	lectin-SERS assay	40:56	lectin-SERS assay	40:56	Rapid and sensitive glycan targeting by lectin-SERS assay.
32452486	6	54	theme	specific	1126:1133	arg1	signatures					1115:1124	different and unique glycan signatures	1087:1124	signatures	1115:1124	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	0	55	dep	targeting	27:35	arg1	assay					52:56	lectin-SERS assay	40:56	lectin-SERS assay	40:56	Rapid and sensitive glycan targeting by lectin-SERS assay.
32452486	7	56	theme	glycomics	1358:1366	arg1	research					1368:1375	glycomics research	1358:1375	glycomics research	1358:1375	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	4	57	theme	WGA	763:765	arg1	lectin					791:796	glycan-binding WGA (wheat germ agglutinin) lectin	748:796	glycan-binding WGA (wheat germ agglutinin) lectin	748:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	58	theme	model	670:674	arg1	glycoprotein					676:687	a model glycoprotein	668:687	a model glycoprotein	668:687	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	5	59	theme	high	945:948	arg1	specificity					957:967	high glycan specificity	945:967	high glycan specificity	945:967	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	4	60	theme	glycan-binding	748:761	arg1	WGA					763:765	glycan-binding WGA	748:765	glycan-binding WGA (wheat germ agglutinin) lectin	748:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	60	theme	glycan-binding	748:761	arg1	agglutinin					779:788	wheat germ agglutinin	768:788	wheat germ agglutinin	768:788	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	61	theme	wheat	768:772	arg1	WGA					763:765	glycan-binding WGA	748:765	glycan-binding WGA (wheat germ agglutinin) lectin	748:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	61	theme	wheat	768:772	arg1	agglutinin					779:788	wheat germ agglutinin	768:788	wheat germ agglutinin	768:788	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	6	62	theme	glycan	1017:1022	arg1	profiles					1024:1031	the surface glycan profiles	1005:1031	the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines	1005:1158	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	2	63	from	proteins	256:263	arg1	differentiation					226:240	rapid and sensitive differentiation	206:240	rapid and sensitive differentiation of glycans on proteins	206:263	Therefore rapid and sensitive differentiation of glycans on proteins is highly desirable.
32452486	4	64	theme	simple	592:597	arg1	strategy					607:614	a simple and new strategy	590:614	a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin	590:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	3	65	theme	Current	286:292	arg1	technologies					294:305	Current technologies	286:305	Current technologies for glycan structural analysis	286:336	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	5	66	theme	glycan	950:955	arg1	specificity					957:967	high glycan specificity	945:967	high glycan specificity	945:967	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	2	67	theme	glycans	245:251	arg1	differentiation					226:240	rapid and sensitive differentiation	206:240	rapid and sensitive differentiation of glycans on proteins	206:263	Therefore rapid and sensitive differentiation of glycans on proteins is highly desirable.
32452486	5	68	theme	glycoprotein	847:858	arg1	solution					860:867	glycoprotein solution	847:867	glycoprotein solution	847:867	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	7	69	theme	powerful	1340:1347	arg1	tool					1349:1352	a powerful tool	1338:1352	a powerful tool for glycomics research	1338:1375	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	6	70	theme	different	1087:1095	arg1	signatures					1115:1124	different and unique glycan signatures	1087:1124	signatures	1115:1124	We extend our technique to examine the surface glycan profiles on two human colorectal cancer cell lines, which show different and unique glycan signatures specific to the target cell lines.
32452486	5	71	theme	lectin-SERS	874:884	arg1	assay					886:890	our lectin-SERS assay	870:890	our lectin-SERS assay	870:890	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
32452486	4	72	theme	new	603:605	arg1	strategy					607:614	a simple and new strategy	590:614	a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin	590:796	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	7	73	theme	real-time	1229:1237	arg1	monitoring					1251:1260	the real-time and in situ monitoring	1225:1260	the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids	1225:1323	Thus, we believe that this method could be potentially used for the real-time and in situ monitoring of glycans on the surface of cells or tissue or in body fluids, and is thus a powerful tool for glycomics research.
32452486	4	74	attach	present	582:588	arg1	assay					816:820	a lectin-SERS assay	802:820	a lectin-SERS assay	802:820	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	4	74	attach	present	582:588	arg2	we					579:580	we	579:580	we	579:580	Herein we present a simple and new strategy for targeting the glycans on a protein (with IgG as a model glycoprotein) using surface-enhanced Raman scattering (SERS) coupled to glycan-binding WGA (wheat germ agglutinin) lectin, in a lectin-SERS assay.
32452486	3	75	from	detection	431:439	arg1	glycans					372:378	glycans	372:378	glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	372:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	3	75	from	detection	431:439	arg1	isolation					359:367	the isolation	355:367	the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories	355:569	Current technologies for glycan structural analysis normally involve the isolation of glycans from proteins, or enrichment of glycopeptides, and detection by mass spectrometry, which requires relatively large amounts of sample and is not able to be used by non-specialist laboratories.
32452486	1	76	theme	many	135:138	arg1	states					148:153	many disease states	135:153	many disease states in which glycans play an essential role	135:193	Glycosylation is an important part of cell signalling that is implicated in many disease states in which glycans play an essential role.
32452486	5	77	with	hours	934:938	arg1	specificity					957:967	high glycan specificity	945:967	high glycan specificity	945:967	With one drop (1 μL) of glycoprotein solution, our lectin-SERS assay can detect as low as 10 ng IgG within two hours with high glycan specificity.
33121334	4	0	dep	altered	875:881	arg1	showed					962:967	showed	962:967	showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics	962:1063	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	5	1	theme	Fv	1113:1114	arg1	glycan					1116:1121	Fv glycan	1113:1121	Fv glycan	1113:1121	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	6	2	gly	Fv-glycosylated	1498:1512	arg1	counterparts					1514:1525	their wild-type Fv-glycosylated counterparts	1482:1525	their wild-type Fv-glycosylated counterparts	1482:1525	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	6	3	theme	neutralization	1388:1401	arg1	potency					1403:1409	neutralization potency	1388:1409	neutralization potency	1388:1409	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	5	4	theme	glycan	1116:1121	arg1	removal					1102:1108	removal	1102:1108	removal of Fv glycan	1102:1121	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	7	5	theme	liquid	1611:1616	arg1	spectrometry					1638:1649	liquid chromatography-mass spectrometry	1611:1649	liquid chromatography-mass spectrometry	1611:1649	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	5	6	theme	low	1258:1260	arg1	polyreactivity					1262:1275	low polyreactivity	1258:1275	low polyreactivity for N6 and VRC07-523	1258:1296	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	3	7	theme	Fv	629:630	arg1	glycans					632:638	Fv glycans	629:638	Fv glycans	629:638	Here we propose a general method to remove Fv glycans and use this method to develop engineered versions of these four antibodies with Fv glycans removed.
33121334	4	8	theme	germline	924:931	arg1	mutants					933:939	germline mutants	924:939	germline mutants for N6 and VRC07-523	924:960	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	4	9	dep	in	1040:1041	arg1	vivo					1043:1046	vivo	1043:1046	vivo	1043:1046	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	3	10	with	versions	682:689	arg1	glycans					724:730	Fv glycans	721:730	Fv glycans removed	721:738	Here we propose a general method to remove Fv glycans and use this method to develop engineered versions of these four antibodies with Fv glycans removed.
33121334	5	11	theme	removed	1196:1202	arg1	glycan					1204:1209	the removed glycan	1192:1209	the removed glycan	1192:1209	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	2	12	theme	chemical	500:507	arg1	heterogeneity					509:521	chemical heterogeneity	500:521	chemical heterogeneity	500:521	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	13	gly	glycosylation	391:403	arg2	sequons					405:411	more N-linked glycosylation sequons	377:411	more N-linked glycosylation sequons	377:411	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	8	14	theme	Fv-glycan-removed	1684:1700	arg1	variants					1702:1709	the Fv-glycan-removed variants	1680:1709	the Fv-glycan-removed variants developed here	1680:1724	With reduced heterogeneity, the Fv-glycan-removed variants developed here may have utility as products for treating or preventing infection by HIV-1.
33121334	2	15	theme	clinical	279:286	arg1	candidates					288:297	Some lead clinical candidates	269:297	Some lead clinical candidates	269:297	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	15	theme	clinical	279:286	arg1	antibodies					310:319	antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523	310:362	antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523	310:362	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	7	16	theme	heterogeneity	1579:1591	arg1	reduction					1557:1565	reduction	1557:1565	reduction of chemical heterogeneity	1557:1591	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	7	16	theme	heterogeneity	1579:1591	arg1	glycan					1546:1551	Fv glycan	1543:1551	Fv glycan	1543:1551	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	3	17	theme	antibodies	705:714	arg1	versions					682:689	engineered versions	671:689	engineered versions of these four antibodies with Fv glycans removed	671:738	Here we propose a general method to remove Fv glycans and use this method to develop engineered versions of these four antibodies with Fv glycans removed.
33121334	2	18	theme	lead	274:277	arg1	candidates					288:297	Some lead clinical candidates	269:297	Some lead clinical candidates	269:297	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	18	theme	lead	274:277	arg1	antibodies					310:319	antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523	310:362	antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523	310:362	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	8	19	theme	reduced	1657:1663	arg1	heterogeneity					1665:1677	reduced heterogeneity	1657:1677	reduced heterogeneity	1657:1677	With reduced heterogeneity, the Fv-glycan-removed variants developed here may have utility as products for treating or preventing infection by HIV-1.
33121334	0	20	theme	HIV-1	91:95	arg1	homogeneity					76:86	the homogeneity	72:86	the homogeneity of HIV-1	72:95	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	2	21	theme	somatic	450:456	arg1	hypermutation					458:470	somatic hypermutation	450:470	somatic hypermutation	450:470	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	4	22	theme	germline	746:753	arg1	residues					755:762	germline residues	746:762	germline residues	746:762	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	4	23	theme	in	1040:1041	arg1	pharmacokinetics					1048:1063	unfavorable in vivo pharmacokinetics	1028:1063	unfavorable in vivo pharmacokinetics	1028:1063	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	5	24	theme	proximal	1180:1187	arg1	residues					1144:1151	aromatic residues	1135:1151	aromatic residues	1135:1151	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	0	25	gly	homogeneity	76:86	arg1	HIV-1					91:95	HIV-1	91:95	HIV-1	91:95	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	6	26	theme	such	1303:1306	arg1	N6-N72LCQ-R18LCD					1318:1333	N6-N72LCQ-R18LCD	1318:1333	N6-N72LCQ-R18LCD	1318:1333	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	6	26	theme	such	1303:1306	arg1	variants					1308:1315	Two such variants	1299:1315	Two such variants	1299:1315	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	6	26	theme	such	1303:1306	arg1	VRC07-523-N72LCQ-R24LCD					1339:1361	VRC07-523-N72LCQ-R24LCD	1339:1361	VRC07-523-N72LCQ-R24LCD	1339:1361	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	5	27	with	variants	1244:1251	arg1	polyreactivity					1262:1275	low polyreactivity	1258:1275	low polyreactivity for N6 and VRC07-523	1258:1296	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	4	28	theme	wild	831:834	arg1	type					836:839	wild type	831:839	wild type	831:839	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	0	29	theme	domain	20:25	arg1	glycosylation					36:48	variable domain N-linked glycosylation	11:48	variable domain N-linked glycosylation	11:48	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	0	30	link	N-linked	27:34	arg1	glycosylation					36:48	variable domain N-linked glycosylation	11:48	variable domain N-linked glycosylation	11:48	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	0	31	theme	variable	11:18	arg1	glycosylation					36:48	variable domain N-linked glycosylation	11:48	variable domain N-linked glycosylation	11:48	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	0	32	theme	neutralizing	105:116	arg1	antibodies					118:127	neutralizing antibodies	105:127	neutralizing antibodies	105:127	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	2	33	contain	have	365:368	arg1	antibodies					310:319	antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523	310:362	antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523	310:362	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	33	contain	have	365:368	arg1	candidates					288:297	Some lead clinical candidates	269:297	Some lead clinical candidates	269:297	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	33	contain	have	365:368	arg2	sequons					405:411	more N-linked glycosylation sequons	377:411	more N-linked glycosylation sequons	377:411	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	33	contain	have	365:368	arg2	one					370:372	one	370:372	one	370:372	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	0	34	theme	glycosylation	36:48	arg1	Removal					0:6	Removal	0:6	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1	0:95	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	3	35	theme	Fv	721:722	arg1	glycans					724:730	Fv glycans	721:730	Fv glycans removed	721:738	Here we propose a general method to remove Fv glycans and use this method to develop engineered versions of these four antibodies with Fv glycans removed.
33121334	7	36	theme	reduction	1557:1565	arg1	removal					1532:1538	The removal	1528:1538	The removal of Fv glycan and reduction of chemical heterogeneity	1528:1591	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	2	37	from	hypermutation	458:470	arg1	domains					431:437	their variable domains	416:437	their variable domains (Fvs) from somatic hypermutation	416:470	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	37	from	hypermutation	458:470	arg1	Fvs					440:442	Fvs	440:442	Fvs	440:442	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	38	theme	glycosylation	391:403	arg1	sequons					405:411	more N-linked glycosylation sequons	377:411	more N-linked glycosylation sequons	377:411	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	0	39	theme	N-linked	27:34	arg1	glycosylation					36:48	variable domain N-linked glycosylation	11:48	variable domain N-linked glycosylation	11:48	Removal of variable domain N-linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies.
33121334	4	40	theme	increased	969:977	arg1	polyreactivity					979:992	increased polyreactivity	969:992	increased polyreactivity	969:992	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	7	41	theme	glycan	1546:1551	arg1	removal					1532:1538	The removal	1528:1538	The removal of Fv glycan and reduction of chemical heterogeneity	1528:1591	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	1	42	dep	treatment	189:197	arg1	the					185:187	the	185:187	the	185:187	Broadly neutralizing antibodies are showing promise in the treatment and prevention of HIV-1, with several now being evaluated clinically.
33121334	1	43	theme	HIV-1	217:221	arg1	prevention					203:212	prevention	203:212	prevention	203:212	Broadly neutralizing antibodies are showing promise in the treatment and prevention of HIV-1, with several now being evaluated clinically.
33121334	1	43	theme	HIV-1	217:221	arg1	treatment					189:197	treatment	189:197	treatment	189:197	Broadly neutralizing antibodies are showing promise in the treatment and prevention of HIV-1, with several now being evaluated clinically.
33121334	4	44	theme	antibody	803:810	arg1	properties					812:821	antibody properties	803:821	antibody properties between wild type and mutant	803:850	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	2	45	theme	variable	422:429	arg1	domains					431:437	their variable domains	416:437	their variable domains (Fvs) from somatic hypermutation	416:470	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	2	45	theme	variable	422:429	arg1	Fvs					440:442	Fvs	440:442	Fvs	440:442	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	5	46	theme	aromatic	1135:1142	arg1	residues					1144:1151	aromatic residues	1135:1151	aromatic residues	1135:1151	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	2	47	theme	antibodies	562:571	arg1	manufacture					541:551	the manufacture	537:551	the manufacture of these antibodies as products	537:583	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	7	48	theme	Fv	1543:1544	arg1	glycan					1546:1551	Fv glycan	1543:1551	Fv glycan	1543:1551	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	2	49	link	N-linked	382:389	arg1	sequons					405:411	more N-linked glycosylation sequons	377:411	more N-linked glycosylation sequons	377:411	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	3	50	theme	general	604:610	arg1	method					612:617	a general method	602:617	a general method to remove Fv glycans	602:638	Here we propose a general method to remove Fv glycans and use this method to develop engineered versions of these four antibodies with Fv glycans removed.
33121334	8	51	contain	have	1730:1733	arg2	products					1746:1753	products	1746:1753	products for treating or preventing infection by HIV-1	1746:1799	With reduced heterogeneity, the Fv-glycan-removed variants developed here may have utility as products for treating or preventing infection by HIV-1.
33121334	8	51	contain	have	1730:1733	arg2	utility					1735:1741	utility	1735:1741	utility	1735:1741	With reduced heterogeneity, the Fv-glycan-removed variants developed here may have utility as products for treating or preventing infection by HIV-1.
33121334	8	51	contain	have	1730:1733	arg1	variants					1702:1709	the Fv-glycan-removed variants	1680:1709	the Fv-glycan-removed variants developed here	1680:1724	With reduced heterogeneity, the Fv-glycan-removed variants developed here may have utility as products for treating or preventing infection by HIV-1.
33121334	6	52	theme	FcRn	1451:1454	arg1	mice					1456:1459	humanized FcRn mice	1441:1459	humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts	1441:1525	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	1	53	theme	Broadly	130:136	arg1	antibodies					151:160	Broadly neutralizing antibodies	130:160	Broadly neutralizing antibodies	130:160	Broadly neutralizing antibodies are showing promise in the treatment and prevention of HIV-1, with several now being evaluated clinically.
33121334	6	54	theme	Fv-glycosylated	1498:1512	arg1	counterparts					1514:1525	their wild-type Fv-glycosylated counterparts	1482:1525	their wild-type Fv-glycosylated counterparts	1482:1525	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	2	55	theme	N-linked	382:389	arg1	sequons					405:411	more N-linked glycosylation sequons	377:411	more N-linked glycosylation sequons	377:411	Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have one or more N-linked glycosylation sequons in their variable domains (Fvs) from somatic hypermutation, and these glycans increase chemical heterogeneity, complicating the manufacture of these antibodies as products.
33121334	1	56	theme	neutralizing	138:149	arg1	antibodies					151:160	Broadly neutralizing antibodies	130:160	Broadly neutralizing antibodies	130:160	Broadly neutralizing antibodies are showing promise in the treatment and prevention of HIV-1, with several now being evaluated clinically.
33121334	6	57	theme	wild-type	1488:1496	arg1	counterparts					1514:1525	their wild-type Fv-glycosylated counterparts	1482:1525	their wild-type Fv-glycosylated counterparts	1482:1525	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	5	58	theme	Fv	1226:1227	arg1	variants					1244:1251	Fv glycan-removed variants	1226:1251	Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523	1226:1296	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33121334	7	59	theme	chemical	1570:1577	arg1	heterogeneity					1579:1591	chemical heterogeneity	1570:1591	chemical heterogeneity	1570:1591	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	3	60	theme	engineered	671:680	arg1	versions					682:689	engineered versions	671:689	engineered versions of these four antibodies with Fv glycans removed	671:738	Here we propose a general method to remove Fv glycans and use this method to develop engineered versions of these four antibodies with Fv glycans removed.
33121334	6	61	theme	humanized	1441:1449	arg1	mice					1456:1459	humanized FcRn mice	1441:1459	humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts	1441:1525	Two such variants, N6-N72LCQ-R18LCD and VRC07-523-N72LCQ-R24LCD, showed thermostability, neutralization potency and breadth, and half-life in humanized FcRn mice that were similar to their wild-type Fv-glycosylated counterparts.
33121334	7	62	theme	chromatography-mass	1618:1636	arg1	spectrometry					1638:1649	liquid chromatography-mass spectrometry	1611:1649	liquid chromatography-mass spectrometry	1611:1649	The removal of Fv glycan and reduction of chemical heterogeneity were confirmed by liquid chromatography-mass spectrometry.
33121334	4	63	theme	unfavorable	1028:1038	arg1	pharmacokinetics					1048:1063	unfavorable in vivo pharmacokinetics	1028:1063	unfavorable in vivo pharmacokinetics	1028:1063	When germline residues were introduced to remove each glycan, antibody properties between wild type and mutant were not significantly altered for CAP256-VRC26.25 and PGT121; however, germline mutants for N6 and VRC07-523 showed increased polyreactivity, which is known to correlate with unfavorable in vivo pharmacokinetics.
33121334	5	64	theme	glycan-removed	1229:1242	arg1	variants					1244:1251	Fv glycan-removed variants	1226:1251	Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523	1226:1296	To reduce polyreactivity induced by removal of Fv glycan, we mutated aromatic residues and arginines structurally proximal to the removed glycan and identified Fv glycan-removed variants with low polyreactivity for N6 and VRC07-523.
33092920	1	0	theme	dairy	172:176	arg1	industry					178:185	the dairy industry	168:185	the dairy industry	168:185	Goat milk oligosaccharides represent an unexplored multi-functional ingredient for the dairy industry.
33092920	6	1	theme	trifucosylated	662:675	arg1	H5N5F3					695:700	H5N5F3	695:700	H5N5F3	695:700	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	6	1	theme	trifucosylated	662:675	arg1	N-glycan					685:692	The triantennary trifucosylated complex N-glycan	645:692	The triantennary trifucosylated complex N-glycan (H5N5F3)	645:701	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	10	2	theme	O-glycans	1186:1194	arg1	content					1196:1202	overall O-glycans content	1178:1202	overall O-glycans content	1178:1202	As lactation progressed, overall O-glycans content decreased by 1.26-fold.
33092920	3	3	theme	high	383:386	arg1	N-glycans					396:404	high mannose N-glycans	383:404	high mannose N-glycans	383:404	Complex N-glycans and high mannose N-glycans constituted 82.1% and 17.9% of the glycan pool, respectively.
33092920	9	4	link	O-linked	1098:1105	arg1	core					1107:1110	O-linked core 2	1098:1112	O-linked core 2	1098:1112	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	7	5	from	decrease	804:811	arg1	fucosylation					858:869	fucosylation	858:869	fucosylation with ongoing lactation	858:892	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	7	5	from	decrease	804:811	arg1	N-glycans					822:830	total N-glycans	816:830	total N-glycans	816:830	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	9	6	link	O-linked	1070:1077	arg1	core					1079:1082	O-linked core 1	1070:1084	O-linked core 1	1070:1084	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	6	7	theme	triantennary	649:660	arg1	H5N5F3					695:700	H5N5F3	695:700	H5N5F3	695:700	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	6	7	theme	triantennary	649:660	arg1	N-glycan					685:692	The triantennary trifucosylated complex N-glycan	645:692	The triantennary trifucosylated complex N-glycan (H5N5F3)	645:701	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	7	8	from	trend	907:911	arg1	milk					922:925	human milk	916:925	human milk	916:925	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	11	9	theme	Neu5Gc-modified	1259:1273	arg1	sialylation					1275:1285	Neu5Gc-modified sialylation	1259:1285	Neu5Gc-modified sialylation	1259:1285	Unlike human milk, Neu5Ac- and Neu5Gc-modified sialylation increased by 4.4 and 2 times, respectively.
33092920	2	10	theme	mass	342:345	arg1	spectrometry					347:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	Here, we qualitatively and quantitatively compared the N/O-glycome at different lactation stages via online hydrophilic interaction chromatography-tandem mass spectrometry.
33092920	12	11	theme	milk	1418:1421	arg1	oligosaccharides					1423:1438	goat milk oligosaccharides	1413:1438	goat milk oligosaccharides	1413:1438	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	2	12	theme	chromatography-tandem	320:340	arg1	spectrometry					347:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	Here, we qualitatively and quantitatively compared the N/O-glycome at different lactation stages via online hydrophilic interaction chromatography-tandem mass spectrometry.
33092920	12	13	theme	goat	1413:1416	arg1	oligosaccharides					1423:1438	goat milk oligosaccharides	1413:1438	goat milk oligosaccharides	1413:1438	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	4	14	with	N-glycans	468:476	arg1	isomers					483:489	isomers	483:489	isomers containing non-bisected antenna complex structures	483:540	N-glycans with isomers containing non-bisected antenna complex structures accounted for 30.8%.
33092920	9	15	theme	O-linked	1070:1077	arg1	core					1079:1082	O-linked core 1	1070:1084	O-linked core 1	1070:1084	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	2	16	theme	interaction	308:318	arg1	spectrometry					347:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	Here, we qualitatively and quantitatively compared the N/O-glycome at different lactation stages via online hydrophilic interaction chromatography-tandem mass spectrometry.
33092920	2	17	theme	hydrophilic	296:306	arg1	spectrometry					347:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	Here, we qualitatively and quantitatively compared the N/O-glycome at different lactation stages via online hydrophilic interaction chromatography-tandem mass spectrometry.
33092920	12	18	theme	oligosaccharides	1423:1438	arg1	development					1448:1458	the development	1444:1458	the development of formula food targeting different age groups	1444:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	12	18	theme	oligosaccharides	1423:1438	arg1	relationship					1397:1408	the structure-function relationship	1374:1408	the structure-function relationship of goat milk oligosaccharides	1374:1438	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	0	19	theme	lactation	67:75	arg1	stages					77:82	different lactation stages	57:82	different lactation stages	57:82	Alteration of the goat milk glycoproteins N/O-glycome at different lactation stages.
33092920	1	20	theme	Goat	85:88	arg1	oligosaccharides					95:110	Goat milk oligosaccharides	85:110	Goat milk oligosaccharides	85:110	Goat milk oligosaccharides represent an unexplored multi-functional ingredient for the dairy industry.
33092920	6	21	theme	first	724:728	arg1	time					730:733	the first time	720:733	the first time	720:733	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	11	22	theme	human	1235:1239	arg1	milk					1241:1244	human milk	1235:1244	human milk	1235:1244	Unlike human milk, Neu5Ac- and Neu5Gc-modified sialylation increased by 4.4 and 2 times, respectively.
33092920	12	23	theme	formula	1463:1469	arg1	groups					1500:1505	formula food targeting different age groups	1463:1505	formula food targeting different age groups	1463:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	7	24	theme	1.66-fold	836:844	arg1	decrease					846:853	1.66-fold decrease	836:853	1.66-fold decrease in fucosylation with ongoing lactation	836:892	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	7	25	from	decrease	846:853	arg1	fucosylation					858:869	fucosylation	858:869	fucosylation with ongoing lactation	858:892	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	7	25	from	decrease	846:853	arg1	N-glycans					822:830	total N-glycans	816:830	total N-glycans	816:830	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	1	26	theme	milk	90:93	arg1	oligosaccharides					95:110	Goat milk oligosaccharides	85:110	Goat milk oligosaccharides	85:110	Goat milk oligosaccharides represent an unexplored multi-functional ingredient for the dairy industry.
33092920	9	27	theme	O-linked	1098:1105	arg1	core					1107:1110	O-linked core 2	1098:1112	O-linked core 2	1098:1112	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	7	28	with	fucosylation	858:869	arg1	lactation					884:892	ongoing lactation	876:892	ongoing lactation	876:892	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	0	29	theme	goat	18:21	arg1	glycoproteins					28:40	the goat milk glycoproteins	14:40	the goat milk glycoproteins	14:40	Alteration of the goat milk glycoproteins N/O-glycome at different lactation stages.
33092920	7	30	theme	ongoing	876:882	arg1	lactation					884:892	ongoing lactation	876:892	ongoing lactation	876:892	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	4	31	theme	non-bisected	502:513	arg1	structures					531:540	non-bisected antenna complex structures	502:540	non-bisected antenna complex structures	502:540	N-glycans with isomers containing non-bisected antenna complex structures accounted for 30.8%.
33092920	0	32	theme	glycoproteins	28:40	arg1	Alteration					0:9	Alteration	0:9	Alteration of the goat milk glycoproteins	0:40	Alteration of the goat milk glycoproteins N/O-glycome at different lactation stages.
33092920	12	33	theme	different	1486:1494	arg1	groups					1500:1505	formula food targeting different age groups	1463:1505	formula food targeting different age groups	1463:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	0	34	from	stages	77:82	arg1	N/O-glycome					42:52	N/O-glycome	42:52	N/O-glycome	42:52	Alteration of the goat milk glycoproteins N/O-glycome at different lactation stages.
33092920	2	35	theme	different	258:266	arg1	stages					278:283	different lactation stages	258:283	different lactation stages	258:283	Here, we qualitatively and quantitatively compared the N/O-glycome at different lactation stages via online hydrophilic interaction chromatography-tandem mass spectrometry.
33092920	4	36	contain	containing	491:500	arg2	structures					531:540	non-bisected antenna complex structures	502:540	non-bisected antenna complex structures	502:540	N-glycans with isomers containing non-bisected antenna complex structures accounted for 30.8%.
33092920	4	36	contain	containing	491:500	arg1	isomers					483:489	isomers	483:489	isomers containing non-bisected antenna complex structures	483:540	N-glycans with isomers containing non-bisected antenna complex structures accounted for 30.8%.
33092920	0	37	theme	milk	23:26	arg1	glycoproteins					28:40	the goat milk glycoproteins	14:40	the goat milk glycoproteins	14:40	Alteration of the goat milk glycoproteins N/O-glycome at different lactation stages.
33092920	10	38	theme	overall	1178:1184	arg1	content					1196:1202	overall O-glycans content	1178:1202	overall O-glycans content	1178:1202	As lactation progressed, overall O-glycans content decreased by 1.26-fold.
33092920	4	39	theme	complex	523:529	arg1	structures					531:540	non-bisected antenna complex structures	502:540	non-bisected antenna complex structures	502:540	N-glycans with isomers containing non-bisected antenna complex structures accounted for 30.8%.
33092920	8	40	theme	Neu5Gc-modified	951:965	arg1	sialylation					967:977	Neu5Gc-modified sialylation	951:977	Neu5Gc-modified sialylation	951:977	Similarly, Neu5Ac- and Neu5Gc-modified sialylation decreased by 1.69 and 3.62 times, respectively.
33092920	3	41	theme	glycan	441:446	arg1	pool					448:451	the glycan pool	437:451	the glycan pool	437:451	Complex N-glycans and high mannose N-glycans constituted 82.1% and 17.9% of the glycan pool, respectively.
33092920	7	42	theme	total	816:820	arg1	N-glycans					822:830	total N-glycans	816:830	total N-glycans	816:830	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	3	43	theme	Complex	361:367	arg1	N-glycans					369:377	Complex N-glycans	361:377	Complex N-glycans	361:377	Complex N-glycans and high mannose N-glycans constituted 82.1% and 17.9% of the glycan pool, respectively.
33092920	4	44	theme	antenna	515:521	arg1	structures					531:540	non-bisected antenna complex structures	502:540	non-bisected antenna complex structures	502:540	N-glycans with isomers containing non-bisected antenna complex structures accounted for 30.8%.
33092920	3	45	theme	pool	448:451	arg1	pool					448:451	the glycan pool	437:451	the glycan pool	437:451	Complex N-glycans and high mannose N-glycans constituted 82.1% and 17.9% of the glycan pool, respectively.
33092920	3	45	theme	pool	448:451	arg1	%					422:422	82.1%	418:422	82.1%	418:422	Complex N-glycans and high mannose N-glycans constituted 82.1% and 17.9% of the glycan pool, respectively.
33092920	3	45	theme	pool	448:451	arg1	%					432:432	17.9%	428:432	17.9% of the glycan pool	428:451	Complex N-glycans and high mannose N-glycans constituted 82.1% and 17.9% of the glycan pool, respectively.
33092920	7	46	theme	1.20-fold	794:802	arg1	decrease					804:811	a 1.20-fold decrease	792:811	a 1.20-fold decrease in total N-glycans	792:830	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	12	47	theme	targeting	1476:1484	arg1	groups					1500:1505	formula food targeting different age groups	1463:1505	formula food targeting different age groups	1463:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	1	48	theme	unexplored	125:134	arg1	ingredient					153:162	an unexplored multi-functional ingredient	122:162	an unexplored multi-functional ingredient for the dairy industry	122:185	Goat milk oligosaccharides represent an unexplored multi-functional ingredient for the dairy industry.
33092920	12	49	theme	groups	1500:1505	arg1	development					1448:1458	the development	1444:1458	the development of formula food targeting different age groups	1444:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	12	49	theme	groups	1500:1505	arg1	relationship					1397:1408	the structure-function relationship	1374:1408	the structure-function relationship of goat milk oligosaccharides	1374:1438	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	12	50	theme	food	1471:1474	arg1	groups					1500:1505	formula food targeting different age groups	1463:1505	formula food targeting different age groups	1463:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	2	51	theme	online	289:294	arg1	spectrometry					347:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	online hydrophilic interaction chromatography-tandem mass spectrometry	289:358	Here, we qualitatively and quantitatively compared the N/O-glycome at different lactation stages via online hydrophilic interaction chromatography-tandem mass spectrometry.
33092920	9	52	theme	O-linked	1125:1132	arg1	core					1134:1137	O-linked core 3	1125:1139	O-linked core 3	1125:1139	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	1	53	theme	multi-functional	136:151	arg1	ingredient					153:162	an unexplored multi-functional ingredient	122:162	an unexplored multi-functional ingredient for the dairy industry	122:185	Goat milk oligosaccharides represent an unexplored multi-functional ingredient for the dairy industry.
33092920	12	54	theme	age	1496:1498	arg1	groups					1500:1505	formula food targeting different age groups	1463:1505	formula food targeting different age groups	1463:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	0	55	gly	glycoproteins	28:40	arg1	glycoproteins					28:40	the goat milk glycoproteins	14:40	the goat milk glycoproteins	14:40	Alteration of the goat milk glycoproteins N/O-glycome at different lactation stages.
33092920	12	56	from	research	1362:1369	arg1	development					1448:1458	the development	1444:1458	the development of formula food targeting different age groups	1444:1505	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	12	56	from	research	1362:1369	arg1	relationship					1397:1408	the structure-function relationship	1374:1408	the structure-function relationship of goat milk oligosaccharides	1374:1438	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	12	57	theme	structure-function	1378:1395	arg1	relationship					1397:1408	the structure-function relationship	1374:1408	the structure-function relationship of goat milk oligosaccharides	1374:1438	These findings will facilitate research on the structure-function relationship of goat milk oligosaccharides and the development of formula food targeting different age groups.
33092920	3	58	theme	mannose	388:394	arg1	N-glycans					396:404	high mannose N-glycans	383:404	high mannose N-glycans	383:404	Complex N-glycans and high mannose N-glycans constituted 82.1% and 17.9% of the glycan pool, respectively.
33092920	9	59	from	core	1079:1082	arg1	O-glycome					1034:1042	the O-glycome	1030:1042	the O-glycome	1030:1042	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	7	60	theme	human	916:920	arg1	milk					922:925	human milk	916:925	human milk	916:925	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	9	61	theme	structures	1054:1063	arg1	structures					1054:1063	structures	1054:1063	structures	1054:1063	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	9	61	theme	structures	1054:1063	arg1	%					1049:1049	46.2%	1045:1049	46.2% of structures	1045:1063	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
33092920	7	62	theme	mature	771:776	arg1	milk					778:781	mature milk	771:781	mature milk	771:781	A comparison between colostrum and mature milk revealed a 1.20-fold decrease in total N-glycans and 1.66-fold decrease in fucosylation with ongoing lactation, echoing the trend in human milk.
33092920	0	63	theme	different	57:65	arg1	stages					77:82	different lactation stages	57:82	different lactation stages	57:82	Alteration of the goat milk glycoproteins N/O-glycome at different lactation stages.
33092920	6	64	gly	trifucosylated	662:675	arg1	H5N5F3					695:700	H5N5F3	695:700	H5N5F3	695:700	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	6	64	gly	trifucosylated	662:675	arg1	N-glycan					685:692	The triantennary trifucosylated complex N-glycan	645:692	The triantennary trifucosylated complex N-glycan (H5N5F3)	645:701	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	2	65	theme	lactation	268:276	arg1	stages					278:283	different lactation stages	258:283	different lactation stages	258:283	Here, we qualitatively and quantitatively compared the N/O-glycome at different lactation stages via online hydrophilic interaction chromatography-tandem mass spectrometry.
33092920	6	66	theme	complex	677:683	arg1	H5N5F3					695:700	H5N5F3	695:700	H5N5F3	695:700	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	6	66	theme	complex	677:683	arg1	N-glycan					685:692	The triantennary trifucosylated complex N-glycan	645:692	The triantennary trifucosylated complex N-glycan (H5N5F3)	645:701	The triantennary trifucosylated complex N-glycan (H5N5F3) was reported for the first time.
33092920	9	67	link	O-linked	1125:1132	arg1	core					1134:1137	O-linked core 3	1125:1139	O-linked core 3	1125:1139	In the O-glycome, 46.2% of structures were O-linked core 1, 23.1% were O-linked core 2, 7.7% were O-linked core 3 and core 4.
34379416	11	0	from	studies	1797:1803	arg1	representation					1737:1750	a truthful representation	1726:1750	a truthful representation of the flexibility and function in in silico studies of glycoproteins	1726:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	10	1	theme	glycosylation	1517:1529	arg1	relevance					1504:1512	a possible functional relevance	1482:1512	a possible functional relevance of glycosylation	1482:1529	Hence, this might point to a possible functional relevance of glycosylation in yeast to act on substrates, while glycosylation seems redundant for the human homologous protein.
34379416	3	2	theme	disulfide	526:534	arg1	PDI					547:549	PDI	547:549	PDI	547:549	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	2	theme	disulfide	526:534	arg1	isomerase					536:544	the multidomain protein disulfide isomerase	502:544	the multidomain protein disulfide isomerase (PDI)	502:550	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	4	3	from	cerevisiae	656:665	arg1	yPDI					631:634	yPDI	631:634	yPDI	631:634	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	4	3	from	cerevisiae	656:665	arg1	PDI					626:628	Yeast PDI	620:628	Yeast PDI (yPDI) from Saccharomyces cerevisiae	620:665	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	11	4	from	function	1775:1782	arg1	studies					1797:1803	in silico studies	1787:1803	in silico studies of glycoproteins	1787:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	1	5	theme	branched	204:211	arg1	oligomers					226:234	branched carbohydrate oligomers	204:234	branched carbohydrate oligomers called glycans	204:249	Secreted proteins of eukaryotes are decorated with branched carbohydrate oligomers called glycans.
34379416	11	6	theme	in	1787:1788	arg1	studies					1797:1803	in silico studies	1787:1803	in silico studies of glycoproteins	1787:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	11	7	theme	function	1775:1782	arg1	representation					1737:1750	a truthful representation	1726:1750	a truthful representation of the flexibility and function in in silico studies of glycoproteins	1726:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	10	8	dep	act	1543:1545	arg1	yeast					1534:1538	yeast	1534:1538	yeast	1534:1538	Hence, this might point to a possible functional relevance of glycosylation in yeast to act on substrates, while glycosylation seems redundant for the human homologous protein.
34379416	2	9	theme	protein	328:334	arg1	dynamics					336:343	protein dynamics	328:343	protein dynamics	328:343	This fact is only starting to be considered for in silico investigations of protein dynamics.
34379416	11	10	from	flexibility	1759:1769	arg1	studies					1797:1803	in silico studies	1787:1803	in silico studies of glycoproteins	1787:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	10	11	theme	human	1606:1610	arg1	protein					1623:1629	the human homologous protein	1602:1629	the human homologous protein	1602:1629	Hence, this might point to a possible functional relevance of glycosylation in yeast to act on substrates, while glycosylation seems redundant for the human homologous protein.
34379416	11	12	theme	glycoproteins	1808:1820	arg1	studies					1797:1803	in silico studies	1787:1803	in silico studies of glycoproteins	1787:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	5	13	theme	yPDI	856:859	arg1	simulations					809:819	simulations	809:819	simulations of glycosylated and unglycosylated yPDI	809:859	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	4	14	gly	glycosylated	670:681	arg2	chains					702:707	asparagine side chains	686:707	asparagine side chains	686:707	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	4	14	gly	glycosylated	670:681	arg1	yPDI					631:634	yPDI	631:634	yPDI	631:634	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	4	14	gly	glycosylated	670:681	arg1	PDI					626:628	Yeast PDI	620:628	Yeast PDI (yPDI) from Saccharomyces cerevisiae	620:665	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	5	15	theme	interactions	924:935	arg1	presence					879:886	the presence	875:886	the presence of glycan-glycan and glycan-protein interactions	875:935	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	8	16	theme	surface	1310:1316	arg1	recess					1318:1323	a surface recess	1308:1323	a surface recess that is present in yPDI	1308:1347	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	8	16	theme	surface	1310:1316	arg1	present					1333:1339	present	1333:1339	present	1333:1339	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	11	17	theme	truthful	1728:1735	arg1	representation					1737:1750	a truthful representation	1726:1750	a truthful representation of the flexibility and function in in silico studies of glycoproteins	1726:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	8	18	attach	present	1333:1339	arg2	present					1333:1339	present	1333:1339	present	1333:1339	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	8	18	attach	present	1333:1339	arg2	recess					1318:1323	a surface recess	1308:1323	a surface recess that is present in yPDI	1308:1347	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	8	18	attach	present	1333:1339	arg1	yPDI					1344:1347	yPDI	1344:1347	yPDI	1344:1347	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	11	19	dep	flexibility	1759:1769	arg1	the					1755:1757	the	1755:1757	the	1755:1757	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	3	20	theme	dynamics	371:378	arg1	simulations					385:395	all-atom molecular dynamics (MD) simulations	352:395	all-atom molecular dynamics (MD) simulations	352:395	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	21	from	chaperone	575:583	arg1	ER					615:616	ER	615:616	ER	615:616	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	21	from	chaperone	575:583	arg1	reticulum					604:612	the endoplasmic reticulum	588:612	the endoplasmic reticulum (ER)	588:617	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	1	22	theme	eukaryotes	174:183	arg1	proteins					162:169	Secreted proteins	153:169	Secreted proteins of eukaryotes	153:183	Secreted proteins of eukaryotes are decorated with branched carbohydrate oligomers called glycans.
34379416	6	23	theme	interdomain	1025:1035	arg1	interactions					1037:1048	interdomain interactions	1025:1048	interdomain interactions	1025:1048	For example, glycosylation reduces interdomain interactions, shifting the conformational ensemble toward more open, extended structures.
34379416	3	24	theme	all-atom	352:359	arg1	simulations					385:395	all-atom molecular dynamics (MD) simulations	352:395	all-atom molecular dynamics (MD) simulations	352:395	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	4	25	theme	asparagine	686:695	arg1	chains					702:707	asparagine side chains	686:707	asparagine side chains	686:707	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	11	26	theme	flexibility	1759:1769	arg1	representation					1737:1750	a truthful representation	1726:1750	a truthful representation of the flexibility and function in in silico studies of glycoproteins	1726:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	0	27	theme	Microsecond	95:105	arg1	Dynamics					117:124	Microsecond Molecular Dynamics	95:124	Microsecond Molecular Dynamics	95:124	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	11	28	dep	in	1787:1788	arg1	silico					1790:1795	silico	1790:1795	silico	1790:1795	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	4	29	theme	sites	748:752	arg1	knowledge					717:725	the knowledge	713:725	the knowledge of its five modified sites	713:752	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	7	30	theme	human	1230:1234	arg1	hPDI					1241:1244	hPDI	1241:1244	hPDI	1241:1244	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	7	30	theme	human	1230:1234	arg1	PDI					1236:1238	human PDI	1230:1238	human PDI (hPDI)	1230:1245	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	3	31	theme	MD	381:382	arg1	simulations					385:395	all-atom molecular dynamics (MD) simulations	352:395	all-atom molecular dynamics (MD) simulations	352:395	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	0	32	theme	Markov	130:135	arg1	Modeling					143:150	Markov State Modeling	130:150	Markov State Modeling	130:150	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	8	33	from	present	1333:1339	arg1	yPDI					1344:1347	yPDI	1344:1347	yPDI	1344:1347	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	6	34	dep	open	1100:1103	arg1	extended					1106:1113	extended	1106:1113	extended	1106:1113	For example, glycosylation reduces interdomain interactions, shifting the conformational ensemble toward more open, extended structures.
34379416	7	35	theme	homologous	1202:1211	arg1	proteins					1213:1220	homologous proteins	1202:1220	homologous proteins such as human PDI (hPDI), which is natively unglycosylated	1202:1279	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	7	35	theme	homologous	1202:1211	arg1	PDI					1236:1238	human PDI	1230:1238	human PDI (hPDI)	1230:1245	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	3	36	theme	Markov	401:406	arg1	modeling					414:421	Markov state modeling	401:421	Markov state modeling (MSM)	401:427	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	36	theme	Markov	401:406	arg1	MSM					424:426	MSM	424:426	MSM	424:426	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	0	37	theme	Conformational	25:38	arg1	Flexibility					40:50	Conformational Flexibility	25:50	Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling	25:150	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	3	38	theme	glycans	457:463	arg1	influence					444:452	the influence	440:452	the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER)	440:617	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	11	39	theme	protein	1682:1688	arg1	dynamics					1690:1697	protein dynamics	1682:1697	protein dynamics	1682:1697	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	0	40	theme	Disulfide	63:71	arg1	Isomerase					73:81	Protein Disulfide Isomerase	55:81	Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling	55:150	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	10	41	theme	functional	1493:1502	arg1	relevance					1504:1512	a possible functional relevance	1482:1512	a possible functional relevance of glycosylation	1482:1529	Hence, this might point to a possible functional relevance of glycosylation in yeast to act on substrates, while glycosylation seems redundant for the human homologous protein.
34379416	4	42	theme	computational	774:786	arg1	modeling					788:795	a realistic computational modeling	762:795	a realistic computational modeling	762:795	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	9	43	theme	yPDI	1380:1383	arg1	glycosylation					1363:1375	glycosylation	1363:1375	glycosylation of yPDI	1363:1383	We find that glycosylation of yPDI facilitates its catalytic site to reach close to this surface recess.
34379416	8	44	located	present	1333:1339	arg2	present					1333:1339	present	1333:1339	present	1333:1339	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	8	44	located	present	1333:1339	arg1	yPDI					1344:1347	yPDI	1344:1347	yPDI	1344:1347	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	8	44	located	present	1333:1339	arg2	recess					1318:1323	a surface recess	1308:1323	a surface recess that is present in yPDI	1308:1347	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	3	45	theme	isomerase	536:544	arg1	flexibility					487:497	the conformational flexibility	468:497	the conformational flexibility	468:497	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	45	theme	isomerase	536:544	arg1	chaperone					575:583	a ubiquitous chaperone	562:583	a ubiquitous chaperone in the endoplasmic reticulum (ER)	562:617	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	46	theme	protein	518:524	arg1	PDI					547:549	PDI	547:549	PDI	547:549	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	46	theme	protein	518:524	arg1	isomerase					536:544	the multidomain protein disulfide isomerase	502:544	the multidomain protein disulfide isomerase (PDI)	502:550	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	2	47	theme	silico	303:308	arg1	investigations					310:323	silico investigations	303:323	silico investigations of protein dynamics	303:343	This fact is only starting to be considered for in silico investigations of protein dynamics.
34379416	9	48	theme	surface	1439:1445	arg1	recess					1447:1452	this surface recess	1434:1452	this surface recess	1434:1452	We find that glycosylation of yPDI facilitates its catalytic site to reach close to this surface recess.
34379416	5	49	gly	glycosylated	824:835	arg1	yPDI					856:859	glycosylated and unglycosylated yPDI	824:859	glycosylated and unglycosylated yPDI	824:859	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	3	50	theme	ubiquitous	564:573	arg1	flexibility					487:497	the conformational flexibility	468:497	the conformational flexibility	468:497	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	50	theme	ubiquitous	564:573	arg1	chaperone					575:583	a ubiquitous chaperone	562:583	a ubiquitous chaperone in the endoplasmic reticulum (ER)	562:617	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	1	51	theme	carbohydrate	213:224	arg1	oligomers					226:234	branched carbohydrate oligomers	204:234	branched carbohydrate oligomers called glycans	204:249	Secreted proteins of eukaryotes are decorated with branched carbohydrate oligomers called glycans.
34379416	5	52	gly	unglycosylated	841:854	arg1	yPDI					856:859	glycosylated and unglycosylated yPDI	824:859	glycosylated and unglycosylated yPDI	824:859	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	2	53	theme	dynamics	336:343	arg1	investigations					310:323	silico investigations	303:323	silico investigations of protein dynamics	303:343	This fact is only starting to be considered for in silico investigations of protein dynamics.
34379416	5	54	theme	glycosylated	824:835	arg1	yPDI					856:859	glycosylated and unglycosylated yPDI	824:859	glycosylated and unglycosylated yPDI	824:859	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	4	55	theme	Yeast	620:624	arg1	yPDI					631:634	yPDI	631:634	yPDI	631:634	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	4	55	theme	Yeast	620:624	arg1	PDI					626:628	Yeast PDI	620:628	Yeast PDI (yPDI) from Saccharomyces cerevisiae	620:665	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	10	56	theme	homologous	1612:1621	arg1	protein					1623:1629	the human homologous protein	1602:1629	the human homologous protein	1602:1629	Hence, this might point to a possible functional relevance of glycosylation in yeast to act on substrates, while glycosylation seems redundant for the human homologous protein.
34379416	3	57	theme	endoplasmic	592:602	arg1	ER					615:616	ER	615:616	ER	615:616	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	57	theme	endoplasmic	592:602	arg1	reticulum					604:612	the endoplasmic reticulum	588:612	the endoplasmic reticulum (ER)	588:617	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	5	58	theme	unglycosylated	841:854	arg1	yPDI					856:859	glycosylated and unglycosylated yPDI	824:859	glycosylated and unglycosylated yPDI	824:859	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	5	59	theme	glycan-protein	909:922	arg1	interactions					924:935	glycan-glycan and glycan-protein interactions	891:935	glycan-glycan and glycan-protein interactions	891:935	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	4	60	theme	side	697:700	arg1	chains					702:707	asparagine side chains	686:707	asparagine side chains	686:707	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	1	61	theme	Secreted	153:160	arg1	proteins					162:169	Secreted proteins	153:169	Secreted proteins of eukaryotes	153:183	Secreted proteins of eukaryotes are decorated with branched carbohydrate oligomers called glycans.
34379416	11	62	from	representation	1737:1750	arg1	studies					1797:1803	in silico studies	1787:1803	in silico studies of glycoproteins	1787:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	0	63	theme	Molecular	107:115	arg1	Dynamics					117:124	Microsecond Molecular Dynamics	95:124	Microsecond Molecular Dynamics	95:124	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	7	64	gly	unglycosylated	1266:1279	arg1	hPDI					1241:1244	hPDI	1241:1244	hPDI	1241:1244	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	7	64	gly	unglycosylated	1266:1279	arg1	PDI					1236:1238	human PDI	1230:1238	human PDI (hPDI)	1230:1245	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	5	65	theme	glycan-glycan	891:903	arg1	interactions					924:935	glycan-glycan and glycan-protein interactions	891:935	glycan-glycan and glycan-protein interactions	891:935	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	3	66	theme	molecular	361:369	arg1	simulations					385:395	all-atom molecular dynamics (MD) simulations	352:395	all-atom molecular dynamics (MD) simulations	352:395	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	5	67	theme	different	974:982	arg1	ways					984:987	different ways	974:987	different ways	974:987	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	4	68	theme	modified	739:746	arg1	sites					748:752	five modified sites	734:752	its five modified sites	730:752	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	0	69	theme	State	137:141	arg1	Modeling					143:150	Markov State Modeling	130:150	Markov State Modeling	130:150	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	5	70	from	flexibility	952:962	arg1	ways					984:987	different ways	974:987	different ways	974:987	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	7	71	theme	proteins	1213:1220	arg1	information					1187:1197	structural information	1176:1197	structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated	1176:1279	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	6	72	theme	open	1100:1103	arg1	structures					1115:1124	more open, extended structures	1095:1124	more open, extended structures	1095:1124	For example, glycosylation reduces interdomain interactions, shifting the conformational ensemble toward more open, extended structures.
34379416	7	73	theme	structural	1176:1185	arg1	information					1187:1197	structural information	1176:1197	structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated	1176:1279	In addition, we compare our results on yPDI with structural information of homologous proteins such as human PDI (hPDI), which is natively unglycosylated.
34379416	5	74	theme	PDI	967:969	arg1	flexibility					952:962	the flexibility	948:962	the flexibility of PDI in different ways	948:987	We compare simulations of glycosylated and unglycosylated yPDI and find that the presence of glycan-glycan and glycan-protein interactions influences the flexibility of PDI in different ways.
34379416	3	75	theme	state	408:412	arg1	modeling					414:421	Markov state modeling	401:421	Markov state modeling (MSM)	401:427	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	75	theme	state	408:412	arg1	MSM					424:426	MSM	424:426	MSM	424:426	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	9	76	gly	glycosylation	1363:1375	arg1	yPDI					1380:1383	yPDI	1380:1383	yPDI	1380:1383	We find that glycosylation of yPDI facilitates its catalytic site to reach close to this surface recess.
34379416	3	77	theme	conformational	472:485	arg1	flexibility					487:497	the conformational flexibility	468:497	the conformational flexibility	468:497	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	77	theme	conformational	472:485	arg1	chaperone					575:583	a ubiquitous chaperone	562:583	a ubiquitous chaperone in the endoplasmic reticulum (ER)	562:617	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	0	78	theme	Protein	55:61	arg1	Isomerase					73:81	Protein Disulfide Isomerase	55:81	Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling	55:150	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	6	79	theme	conformational	1064:1077	arg1	ensemble					1079:1086	the conformational ensemble	1060:1086	the conformational ensemble toward more open, extended structures	1060:1124	For example, glycosylation reduces interdomain interactions, shifting the conformational ensemble toward more open, extended structures.
34379416	11	80	gly	glycoproteins	1808:1820	arg1	glycoproteins					1808:1820	glycoproteins	1808:1820	glycoproteins	1808:1820	We conclude that glycosylation is fundamental for protein dynamics, making it a necessity for a truthful representation of the flexibility and function in in silico studies of glycoproteins.
34379416	0	81	theme	Isomerase	73:81	arg1	Flexibility					40:50	Conformational Flexibility	25:50	Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling	25:150	N-Glycosylation Enhances Conformational Flexibility of Protein Disulfide Isomerase Revealed by Microsecond Molecular Dynamics and Markov State Modeling.
34379416	3	82	theme	multidomain	506:516	arg1	PDI					547:549	PDI	547:549	PDI	547:549	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	82	theme	multidomain	506:516	arg1	isomerase					536:544	the multidomain protein disulfide isomerase	502:544	the multidomain protein disulfide isomerase (PDI)	502:550	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	10	83	theme	possible	1484:1491	arg1	relevance					1504:1512	a possible functional relevance	1482:1512	a possible functional relevance of glycosylation	1482:1529	Hence, this might point to a possible functional relevance of glycosylation in yeast to act on substrates, while glycosylation seems redundant for the human homologous protein.
34379416	4	84	theme	realistic	764:772	arg1	modeling					788:795	a realistic computational modeling	762:795	a realistic computational modeling	762:795	Yeast PDI (yPDI) from Saccharomyces cerevisiae is glycosylated at asparagine side chains and the knowledge of its five modified sites enables a realistic computational modeling.
34379416	8	85	from	yPDI	1344:1347	arg1	recess					1318:1323	a surface recess	1308:1323	a surface recess that is present in yPDI	1308:1347	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	8	85	from	yPDI	1344:1347	arg1	present					1333:1339	present	1333:1339	present	1333:1339	Interestingly, hPDI lacks a surface recess that is present in yPDI.
34379416	3	86	from	influence	444:452	arg1	flexibility					487:497	the conformational flexibility	468:497	the conformational flexibility	468:497	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	3	86	from	influence	444:452	arg1	chaperone					575:583	a ubiquitous chaperone	562:583	a ubiquitous chaperone in the endoplasmic reticulum (ER)	562:617	Using all-atom molecular dynamics (MD) simulations and Markov state modeling (MSM), we unveil the influence of glycans on the conformational flexibility of the multidomain protein disulfide isomerase (PDI), which is a ubiquitous chaperone in the endoplasmic reticulum (ER).
34379416	9	87	theme	catalytic	1401:1409	arg1	site					1411:1414	its catalytic site	1397:1414	its catalytic site to reach close to this surface recess	1397:1452	We find that glycosylation of yPDI facilitates its catalytic site to reach close to this surface recess.
34523671	2	0	from	site	538:541	arg1	sequences					521:529	isoform-specific amino acid sequences	493:529	isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins	493:676	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	6	1	theme	O-Glycosylation	1508:1522	arg1	Prediction					1524:1533	Isoform Specific O-Glycosylation Prediction	1491:1533	Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php)	1491:1578	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	5	2	theme	engineered	1248:1257	arg1	sequons					1259:1265	natural and engineered sequons	1236:1265	natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes	1236:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	2	3	theme	structures	625:634	arg1	production					597:606	production	597:606	production of Core 1 glycan structures in bacteria	597:646	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	4	4	theme	enzymes	1105:1111	arg1	orthologues					1081:1091	various orthologues	1073:1091	various orthologues of critical enzymes	1073:1111	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	7	5	theme	designed	1763:1770	arg1	sequons					1772:1778	our human growth hormone designed sequons	1738:1778	our human growth hormone designed sequons	1738:1778	We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.
34523671	3	6	theme	protein	744:750	arg1	glycoforms					752:761	intact protein glycoforms	737:761	intact protein glycoforms	737:761	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	6	7	theme	measurable	1594:1603	arg1	increase					1605:1612	a measurable increase	1592:1612	a measurable increase in kcat/KM	1592:1623	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	2	8	theme	human	651:655	arg1	proteins					669:676	human therapeutic proteins	651:676	human therapeutic proteins	651:676	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	3	9	theme	sequon	778:783	arg1	mutation					785:792	sequon mutation	778:792	sequon mutation	778:792	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	1	10	theme	human	214:218	arg1	O-glycosylation					231:245	human mucin-type O-glycosylation	214:245	human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases	214:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	3	11	with	RP-HPLC	685:691	arg1	phase					720:724	a novel phenyl bonded phase	698:724	a novel phenyl bonded phase	698:724	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	3	12	dep	in	845:846	arg1	vitro					848:852	vitro	848:852	vitro	848:852	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	3	13	dep	engineered	935:944	arg1	sequon					928:933	sequon	928:933	sequon	928:933	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	1	14	theme	therapeutic	250:260	arg1	proteins					262:269	therapeutic proteins	250:269	therapeutic proteins	250:269	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	7	15	theme	Drosophila	1686:1695	arg1	orthologue					1697:1706	the Drosophila orthologue	1682:1706	the Drosophila orthologue	1682:1706	We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.
34523671	1	16	theme	α-linked	310:317	arg1	GalNAc					319:324	α-linked GalNAc	310:324	α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases	310:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	7	17	dep	designed	1763:1770	arg1	hormone					1755:1761	growth hormone	1748:1761	growth hormone	1748:1761	We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.
34523671	3	18	theme	interferon	905:914	arg1	α-2b					916:919	the naturally O-glycosylated human interferon α-2b	870:919	the naturally O-glycosylated human interferon α-2b	870:919	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	3	19	theme	in	845:846	arg1	modification					854:865	in vitro modification	845:865	in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone	845:965	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	6	20	theme	glycosylation	1641:1653	arg1	efficiency					1655:1664	glycosylation efficiency	1641:1664	glycosylation efficiency	1641:1664	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	5	21	with	properties	1374:1383	arg1	changes					1405:1411	the amino acid changes	1390:1411	the amino acid changes	1390:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	3	22	theme	O-glycosylated	884:897	arg1	α-2b					916:919	the naturally O-glycosylated human interferon α-2b	870:919	the naturally O-glycosylated human interferon α-2b	870:919	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	4	23	theme	engineering	1009:1019	arg1	development					983:993	the development	979:993	the development of our glycan engineering in the bacterial expression system	979:1054	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	5	24	theme	in	1166:1167	arg1	profile					1190:1196	an in vitro enzyme kinetic profile	1163:1196	an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes	1163:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	2	25	theme	enzyme	469:474	arg1	isoforms					452:459	different isoforms	442:459	different isoforms of this enzyme	442:474	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	7	26	theme	human	1798:1802	arg1	enzyme					1804:1809	the human enzyme	1794:1809	the human enzyme	1794:1809	We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.
34523671	5	27	dep	in	1166:1167	arg1	vitro					1169:1173	vitro	1169:1173	vitro	1169:1173	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	5	28	theme	human	1307:1311	arg1	hormone					1320:1326	human growth hormone	1307:1326	human growth hormone	1307:1326	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	0	29	theme	polypeptide	78:88	arg1	isozyme					128:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	5	30	theme	enzyme	1175:1180	arg1	profile					1190:1196	an in vitro enzyme kinetic profile	1163:1196	an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes	1163:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	1	31	theme	bacterial	181:189	arg1	systems					202:208	bacterial expression systems	181:208	bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases	181:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	4	32	theme	development	983:993	arg1	part					971:974	part	971:974	part of the development of our glycan engineering in the bacterial expression system	971:1054	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	0	33	theme	transferase	113:123	arg1	isozyme					128:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	1	34	theme	GT-27	376:380	arg1	family					382:387	the GT-27 family	372:387	the GT-27 family of glycosyltransferases	372:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	3	35	theme	growth	952:957	arg1	hormone					959:965	a sequon engineered human growth hormone	926:965	a sequon engineered human growth hormone	926:965	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	3	36	from	effect	768:773	arg1	initiation					813:822	O-glycosylation initiation	797:822	O-glycosylation initiation	797:822	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	6	37	theme	amino	1465:1469	arg1	sequence					1476:1483	the protein substrate amino acid sequence	1443:1483	the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php)	1443:1578	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	6	38	from	increase	1605:1612	arg1	kcat/KM					1617:1623	kcat/KM	1617:1623	kcat/KM	1617:1623	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	3	39	theme	engineered	935:944	arg1	hormone					959:965	a sequon engineered human growth hormone	926:965	a sequon engineered human growth hormone	926:965	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	5	40	theme	amino	1394:1398	arg1	changes					1405:1411	the amino acid changes	1390:1411	the amino acid changes	1390:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	2	41	theme	Substrate	414:422	arg1	preference					424:433	Substrate preference	414:433	Substrate preference across different isoforms of this enzyme	414:474	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	5	42	theme	GT-27	1215:1219	arg1	orthologues					1221:1231	three related GT-27 orthologues	1201:1231	three related GT-27 orthologues	1201:1231	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	7	43	theme	human	1742:1746	arg1	sequons					1772:1778	our human growth hormone designed sequons	1738:1778	our human growth hormone designed sequons	1738:1778	We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.
34523671	3	44	gly	O-glycosylated	884:897	arg1	α-2b					916:919	the naturally O-glycosylated human interferon α-2b	870:919	the naturally O-glycosylated human interferon α-2b	870:919	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	0	45	theme	sequon	17:22	arg1	engineering					24:34	sequon engineering	17:34	sequon engineering	17:34	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	1	46	theme	GalNAc	319:324	arg1	addition					298:305	the addition	294:305	the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases	294:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	4	47	theme	expression	1038:1047	arg1	system					1049:1054	the bacterial expression system	1024:1054	the bacterial expression system	1024:1054	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	5	48	theme	kinetic	1366:1372	arg1	properties					1374:1383	kinetic properties	1366:1383	kinetic properties with the amino acid changes	1366:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	6	49	theme	substrate	1455:1463	arg1	sequence					1476:1483	the protein substrate amino acid sequence	1443:1483	the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php)	1443:1578	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	4	50	theme	bacterial	1028:1036	arg1	system					1049:1054	the bacterial expression system	1024:1054	the bacterial expression system	1024:1054	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	2	51	theme	amino	510:514	arg1	sequences					521:529	isoform-specific amino acid sequences	493:529	isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins	493:676	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	1	52	from	enzymes	361:367	arg1	family					382:387	the GT-27 family	372:387	the GT-27 family of glycosyltransferases	372:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	4	53	theme	complete	1123:1130	arg1	glycosylation					1132:1144	complete glycosylation	1123:1144	complete glycosylation	1123:1144	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	3	54	theme	bonded	713:718	arg1	phase					720:724	a novel phenyl bonded phase	698:724	a novel phenyl bonded phase	698:724	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	5	55	theme	recombinant	1270:1280	arg1	α2b					1299:1301	recombinant human interferon α2b	1270:1301	recombinant human interferon α2b	1270:1301	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	3	56	theme	novel	700:704	arg1	phenyl					706:711	a novel phenyl	698:711	a novel phenyl bonded phase	698:724	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	5	57	theme	interferon	1288:1297	arg1	α2b					1299:1301	recombinant human interferon α2b	1270:1301	recombinant human interferon α2b	1270:1301	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	4	58	theme	critical	1096:1103	arg1	enzymes					1105:1111	critical enzymes	1096:1111	critical enzymes	1096:1111	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	3	59	theme	intact	737:742	arg1	glycoforms					752:761	intact protein glycoforms	737:761	intact protein glycoforms	737:761	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	1	60	link	α-linked	310:317	arg1	GalNAc					319:324	α-linked GalNAc	310:324	α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases	310:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	2	61	from	production	597:606	arg1	bacteria					639:646	bacteria	639:646	bacteria	639:646	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	5	62	from	profile	1190:1196	arg1	sequons					1259:1265	natural and engineered sequons	1236:1265	natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes	1236:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	6	63	theme	Specific	1499:1506	arg1	Prediction					1524:1533	Isoform Specific O-Glycosylation Prediction	1491:1533	Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php)	1491:1578	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	4	64	from	development	983:993	arg1	system					1049:1054	the bacterial expression system	1024:1054	the bacterial expression system	1024:1054	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	2	65	theme	glycan	618:623	arg1	structures					625:634	Core 1 glycan structures	611:634	Core 1 glycan structures	611:634	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	1	66	gly	O-glycosylation	231:245	arg1	proteins					262:269	therapeutic proteins	250:269	therapeutic proteins	250:269	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	1	67	theme	expression	191:200	arg1	systems					202:208	bacterial expression systems	181:208	bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases	181:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	2	68	theme	therapeutic	657:667	arg1	proteins					669:676	human therapeutic proteins	651:676	human therapeutic proteins	651:676	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	7	69	theme	superior	1715:1722	arg1	activity					1724:1731	superior activity	1715:1731	superior activity	1715:1731	We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.
34523671	3	70	theme	mutation	785:792	arg1	effect					768:773	the effect	764:773	the effect of sequon mutation on O-glycosylation initiation	764:822	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	5	71	from	sequons	1259:1265	arg1	hormone					1320:1326	human growth hormone	1307:1326	human growth hormone	1307:1326	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	5	71	from	sequons	1259:1265	arg1	α2b					1299:1301	recombinant human interferon α2b	1270:1301	recombinant human interferon α2b	1270:1301	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	1	72	theme	mucin-type	220:229	arg1	O-glycosylation					231:245	human mucin-type O-glycosylation	214:245	human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases	214:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	4	73	from	part	971:974	arg1	system					1049:1054	the bacterial expression system	1024:1054	the bacterial expression system	1024:1054	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	2	74	theme	Core	611:614	arg1	structures					625:634	Core 1 glycan structures	611:634	Core 1 glycan structures	611:634	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	5	75	from	change	1356:1361	arg1	properties					1374:1383	kinetic properties	1366:1383	kinetic properties with the amino acid changes	1366:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	3	76	theme	O-glycosylation	797:811	arg1	initiation					813:822	O-glycosylation initiation	797:822	O-glycosylation initiation	797:822	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	1	77	from	O-glycosylation	231:245	arg1	proteins					262:269	therapeutic proteins	250:269	therapeutic proteins	250:269	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	3	78	theme	α-2b	916:919	arg1	modification					854:865	in vitro modification	845:865	in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone	845:965	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	0	79	theme	human	72:76	arg1	isozyme					128:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	3	80	theme	human	899:903	arg1	α-2b					916:919	the naturally O-glycosylated human interferon α-2b	870:919	the naturally O-glycosylated human interferon α-2b	870:919	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	4	81	theme	glycan	1002:1007	arg1	engineering					1009:1019	our glycan engineering	998:1019	our glycan engineering	998:1019	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	0	82	theme	N-acetylgalactosaminyl	90:111	arg1	isozyme					128:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	5	83	theme	growth	1313:1318	arg1	hormone					1320:1326	human growth hormone	1307:1326	human growth hormone	1307:1326	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	6	84	theme	acid	1471:1474	arg1	sequence					1476:1483	the protein substrate amino acid sequence	1443:1483	the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php)	1443:1578	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	0	85	theme	T2	125:126	arg1	isozyme					128:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme	68:134	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	5	86	theme	kinetic	1182:1188	arg1	profile					1190:1196	an in vitro enzyme kinetic profile	1163:1196	an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes	1163:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	2	87	gly	glycosylation	546:558	arg2	glycosylation					546:558	glycosylation	546:558	glycosylation	546:558	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	2	87	gly	glycosylation	546:558	arg2	site					538:541	the site	534:541	the site	534:541	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	3	88	theme	hormone	959:965	arg1	modification					854:865	in vitro modification	845:865	in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone	845:965	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	2	89	theme	glycosylation	546:558	arg1	site					538:541	the site	534:541	the site	534:541	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	2	89	theme	glycosylation	546:558	arg1	glycosylation					546:558	glycosylation	546:558	glycosylation	546:558	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	1	90	dep	serine	329:334	arg1	residues					349:356	residues	349:356	residues	349:356	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	6	91	theme	Isoform	1491:1497	arg1	Prediction					1524:1533	Isoform Specific O-Glycosylation Prediction	1491:1533	Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php)	1491:1578	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	1	92	theme	glycosyltransferases	392:411	arg1	family					382:387	the GT-27 family	372:387	the GT-27 family of glycosyltransferases	372:411	We have been developing bacterial expression systems for human mucin-type O-glycosylation on therapeutic proteins, which is initiated by the addition of α-linked GalNAc to serine or threonine residues by enzymes in the GT-27 family of glycosyltransferases.
34523671	3	93	theme	human	946:950	arg1	hormone					959:965	a sequon engineered human growth hormone	926:965	a sequon engineered human growth hormone	926:965	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	5	94	theme	significant	1344:1354	arg1	change					1356:1361	a significant change	1342:1361	a significant change in kinetic properties with the amino acid changes	1342:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	0	95	theme	engineering	24:34	arg1	Investigation					0:12	Investigation	0:12	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.	0:155	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	5	96	theme	orthologues	1221:1231	arg1	profile					1190:1196	an in vitro enzyme kinetic profile	1163:1196	an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes	1163:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	7	97	theme	growth	1748:1753	arg1	hormone					1755:1761	growth hormone	1748:1761	growth hormone	1748:1761	We showed that the Drosophila orthologue showed superior activity with our human growth hormone designed sequons compared with the human enzyme.
34523671	4	98	theme	various	1073:1079	arg1	orthologues					1081:1091	various orthologues	1073:1091	various orthologues of critical enzymes	1073:1111	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	3	99	gly	glycoforms	752:761	arg1	protein					744:750	intact protein glycoforms	737:761	intact protein glycoforms	737:761	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	0	100	theme	improved	40:47	arg1	O-glycosylation					49:63	improved O-glycosylation	40:63	improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues	40:154	Investigation of sequon engineering for improved O-glycosylation by the human polypeptide N-acetylgalactosaminyl transferase T2 isozyme and two orthologues.
34523671	5	101	theme	natural	1236:1242	arg1	sequons					1259:1265	natural and engineered sequons	1236:1265	natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes	1236:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	2	102	theme	acid	516:519	arg1	sequences					521:529	isoform-specific amino acid sequences	493:529	isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins	493:676	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	2	103	theme	different	442:450	arg1	isoforms					452:459	different isoforms	442:459	different isoforms of this enzyme	442:474	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	6	104	theme	protein	1447:1453	arg1	sequence					1476:1483	the protein substrate amino acid sequence	1443:1483	the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php)	1443:1578	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	4	105	from	system	1049:1054	arg1	part					971:974	part	971:974	part of the development of our glycan engineering in the bacterial expression system	971:1054	As part of the development of our glycan engineering in the bacterial expression system we are surveying various orthologues of critical enzymes to ensure complete glycosylation.
34523671	2	106	theme	isoform-specific	493:508	arg1	sequences					521:529	isoform-specific amino acid sequences	493:529	isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins	493:676	Substrate preference across different isoforms of this enzyme is influenced by isoform-specific amino acid sequences at the site of glycosylation, which we have exploited to engineer production of Core 1 glycan structures in bacteria on human therapeutic proteins.
34523671	3	107	theme	phenyl	706:711	arg1	phase					720:724	a novel phenyl bonded phase	698:724	a novel phenyl bonded phase	698:724	Using RP-HPLC with a novel phenyl bonded phase to resolve intact protein glycoforms, the effect of sequon mutation on O-glycosylation initiation was examined through in vitro modification of the naturally O-glycosylated human interferon α-2b, and a sequon engineered human growth hormone.
34523671	5	108	theme	related	1207:1213	arg1	orthologues					1221:1231	three related GT-27 orthologues	1201:1231	three related GT-27 orthologues	1201:1231	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	6	109	dep	Prediction	1524:1533	arg1	http					1545:1548	http	1545:1548	http	1545:1548	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	6	109	dep	Prediction	1524:1533	arg1	ISOGlyP					1536:1542	ISOGlyP	1536:1542	ISOGlyP	1536:1542	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34523671	5	110	theme	acid	1400:1403	arg1	changes					1405:1411	the amino acid changes	1390:1411	the amino acid changes	1390:1411	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	5	111	theme	human	1282:1286	arg1	α2b					1299:1301	recombinant human interferon α2b	1270:1301	recombinant human interferon α2b	1270:1301	Here we present an in vitro enzyme kinetic profile of three related GT-27 orthologues on natural and engineered sequons in recombinant human interferon α2b and human growth hormone where we show a significant change in kinetic properties with the amino acid changes.
34523671	6	112	dep	ISOGlyP	1536:1542	arg1	//isoglyp.utep.edu/index.php					1550:1577	//isoglyp.utep.edu/index.php	1550:1577	//isoglyp.utep.edu/index.php	1550:1577	It was found that optimizing the protein substrate amino acid sequence using Isoform Specific O-Glycosylation Prediction (ISOGlyP, http://isoglyp.utep.edu/index.php) resulted in a measurable increase in kcat/KM, thus improving glycosylation efficiency.
34647616	7	0	theme	cytotoxic	1552:1560	arg1	activity					1566:1573	higher cytotoxic CDC activity	1545:1573	higher cytotoxic CDC activity with more exposed Gal residues	1545:1604	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	4	1	theme	N-glycans	858:866	arg1	characterization					829:844	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization	752:844	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans	752:866	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	12	2	theme	antibody	2435:2442	arg1	functions					2453:2461	antibody effector functions	2435:2461	antibody effector functions	2435:2461	This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.
34647616	3	3	theme	glycoengineered	484:498	arg1	ovary					516:520	Multiple glycoengineered Chinese hamster ovary	475:520	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	10	4	theme	WT	2129:2130	arg1	antibodies					2132:2141	the defucosylated WT antibodies	2111:2141	the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution	2111:2226	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	8	5	theme	large	1690:1694	arg1	fraction					1696:1703	a large fraction	1688:1703	a large fraction of bi-GlcNAc structures (G0)	1688:1732	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	7	6	theme	antibody	1523:1530	arg1	samples					1532:1538	WT antibody samples	1520:1538	WT antibody samples	1520:1538	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	4	7	theme	spectrometry	816:827	arg1	ionization-time					785:799	Matrix-assisted laser desorption ionization-time	752:799	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans	752:866	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	10	8	theme	ADCC	2174:2177	arg1	activity					2179:2186	the highest overall ADCC activity	2154:2186	the highest overall ADCC activity	2154:2186	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	3	9	theme	anti-CD20	689:697	arg1	WT					704:705	a wild-type anti-CD20 IgG (WT)	677:706	a wild-type anti-CD20 IgG (WT)	677:706	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	3	10	theme	cell	522:525	arg1	lines					527:531	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	8	11	theme	CDC	1756:1758	arg1	activity					1760:1767	the lowest CDC activity	1745:1767	the lowest CDC activity of all WT antibody samples	1745:1794	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	10	12	theme	highest	2158:2164	arg1	activity					2179:2186	the highest overall ADCC activity	2154:2186	the highest overall ADCC activity	2154:2186	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	10	13	theme	F241A	2006:2010	arg1	mutants					2012:2018	the defucosylated WT and F241A mutants	1981:2018	the defucosylated WT and F241A mutants	1981:2018	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	4	14	theme	galactosylation	925:939	arg1	content					957:963	galactosylation and sialylation content	925:963	galactosylation and sialylation content	925:963	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	10	15	theme	WT	1999:2000	arg1	mutants					2012:2018	the defucosylated WT and F241A mutants	1981:2018	the defucosylated WT and F241A mutants	1981:2018	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	5	16	theme	α-2,3-sialylation	1120:1136	arg1	predominance					1074:1085	a predominance	1072:1085	a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans	1072:1196	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	8	17	theme	WT	1776:1777	arg1	samples					1788:1794	all WT antibody samples	1772:1794	all WT antibody samples	1772:1794	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	1	18	theme	conserved	187:195	arg1	site					197:200	a conserved site	185:200	a conserved site within the fragment crystallizable (Fc) region	185:247	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	4	19	theme	sialylation	945:955	arg1	content					957:963	galactosylation and sialylation content	925:963	galactosylation and sialylation content	925:963	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	0	20	from	glycosylation	80:92	arg1	functions					121:129	effector functions	112:129	effector functions	112:129	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	5	21	gly	sialylated	1162:1171	arg1	N-glycans					1188:1196	heavily sialylated F241A antibody N-glycans	1154:1196	heavily sialylated F241A antibody N-glycans	1154:1196	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	3	22	theme	F241A	737:741	arg1	mutant					744:749	alanine (F241A) mutant	728:749	alanine (F241A) mutant	728:749	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	6	23	theme	Man5	1384:1387	arg1	groups					1389:1394	Man5 groups	1384:1394	Man5 groups	1384:1394	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	8	24	theme	samples	1788:1794	arg1	activity					1760:1767	the lowest CDC activity	1745:1767	the lowest CDC activity of all WT antibody samples	1745:1794	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	4	25	theme	F241A	886:890	arg1	mutation					892:899	the F241A mutation	882:899	the F241A mutation	882:899	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	7	26	theme	cytotoxicity	1441:1452	arg1	analysis					1460:1467	Further complement-dependent cytotoxicity (CDC) analysis	1412:1467	Further complement-dependent cytotoxicity (CDC) analysis	1412:1467	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	3	27	theme	alanine	728:734	arg1	mutant					744:749	alanine (F241A) mutant	728:749	alanine (F241A) mutant	728:749	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	6	28	theme	GlcNAc	1373:1378	arg1	levels					1354:1359	levels	1354:1359	levels of terminal GlcNAc and Man5 groups	1354:1394	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	7	29	theme	Further	1412:1418	arg1	analysis					1460:1467	Further complement-dependent cytotoxicity (CDC) analysis	1412:1467	Further complement-dependent cytotoxicity (CDC) analysis	1412:1467	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	10	30	theme	acid	2210:2213	arg1	substitution					2215:2226	sialic acid substitution	2203:2226	sialic acid substitution	2203:2226	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	1	31	theme	N-glycan	136:143	arg1	attribute					281:289	a critical antibody quality attribute	253:289	a critical antibody quality attribute whose structural variability can also impact antibody function	253:352	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	1	31	theme	N-glycan	136:143	arg1	pattern					145:151	The N-glycan pattern	132:151	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region,	132:248	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	12	32	theme	protein	2386:2392	arg1	engineering					2394:2404	protein engineering	2386:2404	protein engineering	2386:2404	This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.
34647616	10	33	theme	ADCC	2045:2048	arg1	performance					2050:2060	enhanced in vitro ADCC performance	2027:2060	enhanced in vitro ADCC performance	2027:2060	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	0	34	theme	fine-tune	61:69	arg1	glycosylation					80:92	fine-tune antibody glycosylation	61:92	fine-tune antibody glycosylation	61:92	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	5	35	theme	antibody	1179:1186	arg1	N-glycans					1188:1196	heavily sialylated F241A antibody N-glycans	1154:1196	heavily sialylated F241A antibody N-glycans	1154:1196	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	1	36	theme	IgG	159:161	arg1	antibody					163:170	an IgG antibody	156:170	an IgG antibody	156:170	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	7	37	theme	F241A	1635:1639	arg1	mutants					1641:1647	their individual F241A mutants	1618:1647	their individual F241A mutants	1618:1647	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	7	38	theme	complement-dependent	1420:1439	arg1	CDC					1455:1457	CDC	1455:1457	CDC	1455:1457	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	7	38	theme	complement-dependent	1420:1439	arg1	cytotoxicity					1441:1452	complement-dependent cytotoxicity	1420:1452	Further complement-dependent cytotoxicity (CDC) analysis	1412:1467	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	1	39	theme	antibody	336:343	arg1	function					345:352	antibody function	336:352	antibody function	336:352	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	12	40	theme	effector	2444:2451	arg1	functions					2453:2461	antibody effector functions	2435:2461	antibody effector functions	2435:2461	This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.
34647616	5	41	theme	sialylated	1162:1171	arg1	N-glycans					1188:1196	heavily sialylated F241A antibody N-glycans	1154:1196	heavily sialylated F241A antibody N-glycans	1154:1196	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	11	42	theme	FcγRIIIA	2243:2250	arg1	binding					2261:2267	the FcγRIIIA receptor binding	2239:2267	the FcγRIIIA receptor binding by antibodies	2239:2281	Moreover, the FcγRIIIA receptor binding by antibodies did not always correspond directly with ADCC result.
34647616	2	43	theme	cell	410:413	arg1	lines					415:419	cell lines	410:419	cell lines as well as Fc amino acid mutations	410:454	For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied.
34647616	1	44	theme	critical	255:262	arg1	attribute					281:289	a critical antibody quality attribute	253:289	a critical antibody quality attribute whose structural variability can also impact antibody function	253:352	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	1	44	theme	critical	255:262	arg1	pattern					145:151	The N-glycan pattern	132:151	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region,	132:248	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	9	45	theme	CDC	1842:1844	arg1	activity					1846:1853	a higher CDC activity	1833:1853	a higher CDC activity	1833:1853	Furthermore, for the F241A mutants, a higher CDC activity was observed for α-2,6- compared to α-2,3-sialylation.
34647616	4	46	theme	ionization-time	785:799	arg1	characterization					829:844	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization	752:844	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans	752:866	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	1	47	theme	quality	273:279	arg1	attribute					281:289	a critical antibody quality attribute	253:289	a critical antibody quality attribute whose structural variability can also impact antibody function	253:352	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	1	47	theme	quality	273:279	arg1	pattern					145:151	The N-glycan pattern	132:151	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region,	132:248	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	11	48	theme	receptor	2252:2259	arg1	binding					2261:2267	the FcγRIIIA receptor binding	2239:2267	the FcγRIIIA receptor binding by antibodies	2239:2281	Moreover, the FcγRIIIA receptor binding by antibodies did not always correspond directly with ADCC result.
34647616	7	49	theme	exposed	1585:1591	arg1	residues					1597:1604	more exposed Gal residues	1580:1604	more exposed Gal residues	1580:1604	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	2	50	theme	amino	435:439	arg1	mutations					446:454	Fc amino acid mutations	432:454	cell lines as well as Fc amino acid mutations	410:454	For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied.
34647616	1	51	attach	attached	173:180	arg2	antibody					163:170	an IgG antibody	156:170	an IgG antibody	156:170	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	1	51	attach	attached	173:180	arg3	site					197:200	a conserved site	185:200	a conserved site within the fragment crystallizable (Fc) region	185:247	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	4	52	theme	flight	804:809	arg1	spectrometry					816:827	flight mass spectrometry	804:827	flight mass spectrometry	804:827	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	0	53	theme	glycoengineering	41:56	arg1	interplay					4:12	The interplay	0:12	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.	0:130	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	10	54	theme	defucosylated	2115:2127	arg1	antibodies					2132:2141	the defucosylated WT antibodies	2111:2141	the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution	2111:2226	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	12	55	theme	glycan	2510:2515	arg1	composition					2517:2527	glycan composition	2510:2527	glycan composition	2510:2527	This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.
34647616	10	56	theme	Antibody-dependent	1910:1927	arg1	ADCC					1952:1955	ADCC	1952:1955	ADCC	1952:1955	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	10	56	theme	Antibody-dependent	1910:1927	arg1	cytotoxicity					1938:1949	Antibody-dependent cellular cytotoxicity	1910:1949	Antibody-dependent cellular cytotoxicity (ADCC) analysis	1910:1965	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	7	57	theme	CDC	1562:1564	arg1	activity					1566:1573	higher cytotoxic CDC activity	1545:1573	higher cytotoxic CDC activity with more exposed Gal residues	1545:1604	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	5	58	theme	recombinant	1018:1028	arg1	α-2,6-sialyltransferase					1036:1058	recombinant human α-2,6-sialyltransferase	1018:1058	recombinant human α-2,6-sialyltransferase	1018:1058	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	2	59	from	glycoengineering	390:405	arg1	lines					415:419	cell lines	410:419	cell lines as well as Fc amino acid mutations	410:454	For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied.
34647616	2	59	from	glycoengineering	390:405	arg1	mutations					446:454	Fc amino acid mutations	432:454	cell lines as well as Fc amino acid mutations	410:454	For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied.
34647616	12	60	theme	practical	2477:2485	arg1	approaches					2487:2496	practical approaches	2477:2496	practical approaches for varying glycan composition and functionalities during antibody development	2477:2575	This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.
34647616	4	61	theme	laser	768:772	arg1	ionization-time					785:799	Matrix-assisted laser desorption ionization-time	752:799	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans	752:866	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	3	62	theme	Chinese	500:506	arg1	ovary					516:520	Multiple glycoengineered Chinese hamster ovary	475:520	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	8	63	theme	bi-GlcNAc	1708:1716	arg1	G0					1730:1731	G0	1730:1731	G0	1730:1731	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	8	63	theme	bi-GlcNAc	1708:1716	arg1	structures					1718:1727	bi-GlcNAc structures	1708:1727	bi-GlcNAc structures (G0)	1708:1732	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	1	64	theme	crystallizable	222:235	arg1	region					242:247	the fragment crystallizable (Fc) region	209:247	the fragment crystallizable (Fc) region	209:247	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	7	65	theme	higher	1545:1550	arg1	activity					1566:1573	higher cytotoxic CDC activity	1545:1573	higher cytotoxic CDC activity with more exposed Gal residues	1545:1604	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	5	66	theme	α-2,6-sialyltransferase	1036:1058	arg1	overexpression					1000:1013	overexpression	1000:1013	overexpression of recombinant human α-2,6-sialyltransferase	1000:1058	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	8	67	theme	WT	1670:1671	arg1	antibody					1673:1680	the FUT8KO WT antibody	1659:1680	the FUT8KO WT antibody	1659:1680	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	3	68	theme	wild-type	679:687	arg1	WT					704:705	a wild-type anti-CD20 IgG (WT)	677:706	a wild-type anti-CD20 IgG (WT)	677:706	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	3	69	theme	Multiple	475:482	arg1	ovary					516:520	Multiple glycoengineered Chinese hamster ovary	475:520	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	1	70	theme	Fc	238:239	arg1	region					242:247	the fragment crystallizable (Fc) region	209:247	the fragment crystallizable (Fc) region	209:247	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	4	71	theme	antibody	849:856	arg1	N-glycans					858:866	antibody N-glycans	849:866	antibody N-glycans	849:866	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	10	72	theme	cytotoxicity	1938:1949	arg1	analysis					1958:1965	Antibody-dependent cellular cytotoxicity (ADCC) analysis	1910:1965	Antibody-dependent cellular cytotoxicity (ADCC) analysis	1910:1965	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	8	73	with	antibody	1673:1680	arg1	fraction					1696:1703	a large fraction	1688:1703	a large fraction of bi-GlcNAc structures (G0)	1688:1732	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	7	74	theme	WT	1520:1521	arg1	samples					1532:1538	WT antibody samples	1520:1538	WT antibody samples	1520:1538	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	7	75	theme	production	1502:1511	arg1	cells					1513:1517	the production cells	1498:1517	the production cells	1498:1517	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	11	76	theme	ADCC	2323:2326	arg1	result					2328:2333	ADCC result	2323:2333	ADCC result	2323:2333	Moreover, the FcγRIIIA receptor binding by antibodies did not always correspond directly with ADCC result.
34647616	6	77	theme	terminal	1327:1334	arg1	Gal					1336:1338	terminal Gal	1327:1338	terminal Gal	1327:1338	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	3	78	theme	ovary	516:520	arg1	lines					527:531	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	7	79	with	activity	1566:1573	arg1	residues					1597:1604	more exposed Gal residues	1580:1604	more exposed Gal residues	1580:1604	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	1	80	theme	antibody	163:170	arg1	attribute					281:289	a critical antibody quality attribute	253:289	a critical antibody quality attribute whose structural variability can also impact antibody function	253:352	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	1	80	theme	antibody	163:170	arg1	pattern					145:151	The N-glycan pattern	132:151	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region,	132:248	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	4	81	theme	mass	811:814	arg1	spectrometry					816:827	flight mass spectrometry	804:827	flight mass spectrometry	804:827	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	10	82	theme	overall	2166:2172	arg1	activity					2179:2186	the highest overall ADCC activity	2154:2186	the highest overall ADCC activity	2154:2186	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	3	83	theme	IgG	699:701	arg1	WT					704:705	a wild-type anti-CD20 IgG (WT)	677:706	a wild-type anti-CD20 IgG (WT)	677:706	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34647616	6	84	theme	N-glycans	1312:1320	arg1	content					1301:1307	the content	1297:1307	the content of N-glycans	1297:1320	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	8	85	theme	lowest	1749:1754	arg1	activity					1760:1767	the lowest CDC activity	1745:1767	the lowest CDC activity of all WT antibody samples	1745:1794	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	10	86	theme	sialic	2203:2208	arg1	substitution					2215:2226	sialic acid substitution	2203:2226	sialic acid substitution	2203:2226	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	6	87	theme	WT	1399:1400	arg1	antibody					1402:1409	WT antibody	1399:1409	WT antibody	1399:1409	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	10	88	theme	defucosylated	1985:1997	arg1	mutants					2012:2018	the defucosylated WT and F241A mutants	1981:2018	the defucosylated WT and F241A mutants	1981:2018	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	6	89	theme	groups	1389:1394	arg1	levels					1354:1359	levels	1354:1359	levels of terminal GlcNAc and Man5 groups	1354:1394	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	10	90	theme	enhanced	2027:2034	arg1	performance					2050:2060	enhanced in vitro ADCC performance	2027:2060	enhanced in vitro ADCC performance	2027:2060	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	8	91	theme	antibody	1779:1786	arg1	samples					1788:1794	all WT antibody samples	1772:1794	all WT antibody samples	1772:1794	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	6	92	theme	terminal	1364:1371	arg1	GlcNAc					1373:1378	terminal GlcNAc	1364:1378	terminal GlcNAc	1364:1378	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	5	93	theme	α-2,6-sialylation	1090:1106	arg1	predominance					1074:1085	a predominance	1072:1085	a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans	1072:1196	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	0	94	from	impact	102:107	arg1	functions					121:129	effector functions	112:129	effector functions	112:129	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	6	95	theme	core	1276:1279	arg1	fucose					1281:1286	core fucose	1276:1286	core fucose	1276:1286	Interestingly, knocking out α-1,6-fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N-glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody.
34647616	0	96	theme	antibody	71:78	arg1	glycosylation					80:92	fine-tune antibody glycosylation	61:92	fine-tune antibody glycosylation	61:92	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	7	97	contain	have	1540:1543	arg2	activity					1566:1573	higher cytotoxic CDC activity	1545:1573	higher cytotoxic CDC activity with more exposed Gal residues	1545:1604	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	7	97	contain	have	1540:1543	arg1	samples					1532:1538	WT antibody samples	1520:1538	WT antibody samples	1520:1538	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	10	98	dep	showed	2020:2025	arg1	compared					2062:2069	compared	2062:2069	compared	2062:2069	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	7	99	theme	individual	1624:1633	arg1	mutants					1641:1647	their individual F241A mutants	1618:1647	their individual F241A mutants	1618:1647	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	10	100	dep	in	2036:2037	arg1	vitro					2039:2043	vitro	2039:2043	vitro	2039:2043	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	10	101	theme	fucosylated	2080:2090	arg1	counterparts					2092:2103	their fucosylated counterparts	2074:2103	their fucosylated counterparts	2074:2103	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	0	102	theme	effector	112:119	arg1	functions					121:129	effector functions	112:129	effector functions	112:129	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	0	103	gly	glycosylation	80:92	arg1	functions					121:129	effector functions	112:129	effector functions	112:129	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	4	104	theme	glycan	969:974	arg1	branching					976:984	glycan branching	969:984	glycan branching	969:984	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	10	105	gly	defucosylated	2115:2127	arg1	antibodies					2132:2141	the defucosylated WT antibodies	2111:2141	the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution	2111:2226	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	5	106	theme	F241A	1173:1177	arg1	N-glycans					1188:1196	heavily sialylated F241A antibody N-glycans	1154:1196	heavily sialylated F241A antibody N-glycans	1154:1196	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	0	107	theme	protein	17:23	arg1	interplay					4:12	The interplay	0:12	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.	0:130	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	10	108	gly	defucosylated	1985:1997	arg1	mutants					2012:2018	the defucosylated WT and F241A mutants	1981:2018	the defucosylated WT and F241A mutants	1981:2018	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	9	109	theme	higher	1835:1840	arg1	activity					1846:1853	a higher CDC activity	1833:1853	a higher CDC activity	1833:1853	Furthermore, for the F241A mutants, a higher CDC activity was observed for α-2,6- compared to α-2,3-sialylation.
34647616	12	110	theme	antibody	2556:2563	arg1	development					2565:2575	antibody development	2556:2575	antibody development	2556:2575	This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.
34647616	1	111	theme	antibody	264:271	arg1	attribute					281:289	a critical antibody quality attribute	253:289	a critical antibody quality attribute whose structural variability can also impact antibody function	253:352	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	1	111	theme	antibody	264:271	arg1	pattern					145:151	The N-glycan pattern	132:151	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region,	132:248	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	10	112	gly	fucosylated	2080:2090	arg1	counterparts					2092:2103	their fucosylated counterparts	2074:2103	their fucosylated counterparts	2074:2103	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	2	113	theme	acid	441:444	arg1	mutations					446:454	Fc amino acid mutations	432:454	cell lines as well as Fc amino acid mutations	410:454	For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied.
34647616	4	114	theme	desorption	774:783	arg1	ionization-time					785:799	Matrix-assisted laser desorption ionization-time	752:799	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans	752:866	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	9	115	theme	F241A	1818:1822	arg1	mutants					1824:1830	the F241A mutants	1814:1830	the F241A mutants	1814:1830	Furthermore, for the F241A mutants, a higher CDC activity was observed for α-2,6- compared to α-2,3-sialylation.
34647616	10	116	theme	in	2036:2037	arg1	performance					2050:2060	enhanced in vitro ADCC performance	2027:2060	enhanced in vitro ADCC performance	2027:2060	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	7	117	theme	Gal	1593:1595	arg1	residues					1597:1604	more exposed Gal residues	1580:1604	more exposed Gal residues	1580:1604	Further complement-dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants.
34647616	2	118	theme	Fc	432:433	arg1	mutations					446:454	Fc amino acid mutations	432:454	cell lines as well as Fc amino acid mutations	410:454	For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied.
34647616	10	119	theme	cellular	1929:1936	arg1	ADCC					1952:1955	ADCC	1952:1955	ADCC	1952:1955	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	10	119	theme	cellular	1929:1936	arg1	cytotoxicity					1938:1949	Antibody-dependent cellular cytotoxicity	1910:1949	Antibody-dependent cellular cytotoxicity (ADCC) analysis	1910:1965	Antibody-dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution.
34647616	1	120	theme	structural	297:306	arg1	variability					308:318	variability	308:318	variability	308:318	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	0	121	dep	protein	17:23	arg1	engineering					25:35	engineering	25:35	engineering	25:35	The interplay of protein engineering and glycoengineering to fine-tune antibody glycosylation and its impact on effector functions.
34647616	8	122	theme	FUT8KO	1663:1668	arg1	antibody					1673:1680	the FUT8KO WT antibody	1659:1680	the FUT8KO WT antibody	1659:1680	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	8	123	theme	structures	1718:1727	arg1	fraction					1696:1703	a large fraction	1688:1703	a large fraction of bi-GlcNAc structures (G0)	1688:1732	However, the FUT8KO WT antibody, with a large fraction of bi-GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples.
34647616	1	124	theme	fragment	213:220	arg1	region					242:247	the fragment crystallizable (Fc) region	209:247	the fragment crystallizable (Fc) region	209:247	The N-glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function.
34647616	5	125	theme	human	1030:1034	arg1	α-2,6-sialyltransferase					1036:1058	recombinant human α-2,6-sialyltransferase	1018:1058	recombinant human α-2,6-sialyltransferase	1018:1058	Furthermore, overexpression of recombinant human α-2,6-sialyltransferase resulted in a predominance of α-2,6-sialylation rather than α-2,3-sialylation for both WT and heavily sialylated F241A antibody N-glycans.
34647616	4	126	theme	Matrix-assisted	752:766	arg1	ionization-time					785:799	Matrix-assisted laser desorption ionization-time	752:799	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans	752:866	Matrix-assisted laser desorption ionization-time of flight mass spectrometry characterization of antibody N-glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching.
34647616	3	127	theme	hamster	508:514	arg1	ovary					516:520	Multiple glycoengineered Chinese hamster ovary	475:520	Multiple glycoengineered Chinese hamster ovary cell lines	475:531	Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α-2,6-sialylated (ST6KI), and defucosylated α-2,6-sialylated (FUT8KOST6KI), expressing either a wild-type anti-CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant.
34910238	6	0	theme	GlcNAc	1275:1280	arg1	transferases					1282:1293	human GlcNAc transferases I and II	1269:1302	human GlcNAc transferases I and II	1269:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	0	theme	GlcNAc	1275:1280	arg1	II					1301:1302	II	1301:1302	II	1301:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	0	theme	GlcNAc	1275:1280	arg1	I					1295:1295	I	1295:1295	I	1295:1295	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	10	1	theme	structure	1800:1808	arg1	formation					1771:1779	formation	1771:1779	formation of target N-glycan structure	1771:1808	• Growth medium supplementation increases formation of target N-glycan structure.
34910238	3	2	theme	disrupted	590:598	arg1	oligosaccharide					613:627	a disrupted lipid-linked oligosaccharide	588:627	a disrupted lipid-linked oligosaccharide synthesis pathway	588:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	9	3	theme	Genetic	1649:1655	arg1	constructs					1657:1666	• Genetic constructs	1647:1666	• Genetic constructs	1647:1666	• Genetic constructs impact the activities of the expressed glycosyltransferases.
34910238	2	4	theme	therapeutic	341:351	arg1	proteins					353:360	therapeutic proteins	341:360	therapeutic proteins	341:360	Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts.
34910238	4	5	theme	4-epimerase	809:819	arg1	domain					821:826	a UDP-glucose 4-epimerase domain	795:826	a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe	795:857	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	6	6	from	optimization	1235:1246	arg1	medium					1353:1358	the growth medium	1342:1358	the growth medium	1342:1358	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	7	theme	glucosamine	1327:1337	arg1	optimization					1235:1246	optimization	1235:1246	optimization of the expression of human GlcNAc transferases I and II	1235:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	7	theme	glucosamine	1327:1337	arg1	supplementation					1308:1322	supplementation	1308:1322	supplementation	1308:1322	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	1	8	theme	important	119:127	arg1	N-glycosylation					97:111	N-glycosylation	97:111	N-glycosylation	97:111	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	1	8	theme	important	119:127	arg1	modification					147:158	an important posttranslational modification	116:158	an important posttranslational modification affecting the properties and quality of therapeutic proteins	116:219	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	3	9	from	development	410:420	arg1	strain					517:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain	477:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway	477:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	9	10	theme	glycosyltransferases	1707:1726	arg1	activities					1679:1688	the activities	1675:1688	the activities of the expressed glycosyltransferases	1675:1726	• Genetic constructs impact the activities of the expressed glycosyltransferases.
34910238	3	11	link	lipid-linked	600:611	arg1	oligosaccharide					613:627	a disrupted lipid-linked oligosaccharide	588:627	a disrupted lipid-linked oligosaccharide synthesis pathway	588:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	3	12	from	characterization	426:441	arg1	strain					517:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain	477:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway	477:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	5	13	theme	digalactosylated	972:987	arg1	glycans					1002:1008	digalactosylated complex-type glycans	972:1008	digalactosylated complex-type glycans	972:1008	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	5	14	theme	extracellular	1020:1032	arg1	galactose					1034:1042	extracellular galactose	1020:1042	extracellular galactose	1020:1042	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	5	15	theme	UDP-glucose	1101:1111	arg1	domain					1125:1130	the UDP-glucose 4-epimerase domain	1097:1130	the UDP-glucose 4-epimerase domain	1097:1130	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	5	16	theme	UDP-glucose	904:914	arg1	domain					928:933	the UDP-glucose 4-epimerase domain	900:933	the UDP-glucose 4-epimerase domain	900:933	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	0	17	theme	galactosylated	14:27	arg1	N-glycans					42:50	galactosylated complex-type N-glycans	14:50	galactosylated complex-type N-glycans	14:50	Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae.
34910238	5	18	theme	domain	928:933	arg1	presence					888:895	the presence	884:895	the presence of the UDP-glucose 4-epimerase domain	884:933	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	5	18	theme	domain	928:933	arg1	beneficial					939:948	beneficial	939:948	beneficial	939:948	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	1	19	theme	proteins	212:219	arg1	properties					174:183	properties	174:183	properties	174:183	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	1	19	theme	proteins	212:219	arg1	quality					189:195	quality	189:195	quality	189:195	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	5	20	attach	linked	1170:1175	arg1	processes					1186:1194	other processes	1180:1194	other processes than its catalytic activity	1180:1222	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	5	20	attach	linked	1170:1175	arg2	impact					1087:1092	the positive impact	1074:1092	the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process	1074:1161	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	0	21	from	Production	0:9	arg1	cerevisiae					85:94	glycoengineered Saccharomyces cerevisiae	55:94	glycoengineered Saccharomyces cerevisiae	55:94	Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae.
34910238	1	22	dep	properties	174:183	arg1	the					170:172	the	170:172	the	170:172	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	10	23	theme	•	1729:1729	arg1	supplementation					1745:1759	• Growth medium supplementation	1729:1759	• Growth medium supplementation	1729:1759	• Growth medium supplementation increases formation of target N-glycan structure.
34910238	8	24	theme	•	1569:1569	arg1	cerevisiae					1601:1610	• Glycoengineered Saccharomyces cerevisiae	1569:1610	• Glycoengineered Saccharomyces cerevisiae	1569:1610	KEY POINTS: • Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.
34910238	6	25	theme	expression	1255:1264	arg1	optimization					1235:1246	optimization	1235:1246	optimization of the expression of human GlcNAc transferases I and II	1235:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	25	theme	expression	1255:1264	arg1	supplementation					1308:1322	supplementation	1308:1322	supplementation	1308:1322	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	3	26	theme	strategy	465:472	arg1	characterization					426:441	characterization	426:441	characterization	426:441	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	3	26	theme	strategy	465:472	arg1	development					410:420	development	410:420	development	410:420	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	8	27	theme	Saccharomyces	1587:1599	arg1	cerevisiae					1601:1610	• Glycoengineered Saccharomyces cerevisiae	1569:1610	• Glycoengineered Saccharomyces cerevisiae	1569:1610	KEY POINTS: • Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.
34910238	3	28	theme	Δalg11	510:515	arg1	strain					517:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain	477:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway	477:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	5	29	from	impact	1087:1092	arg1	process					1155:1161	the galactosylation process	1135:1161	the galactosylation process	1135:1161	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	5	30	theme	domain	1125:1130	arg1	impact					1087:1092	the positive impact	1074:1092	the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process	1074:1161	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	7	31	theme	yeast	1543:1547	arg1	strain					1549:1554	the glycoengineered yeast strain	1523:1554	the glycoengineered yeast strain	1523:1554	Additionally, we provide further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain.
34910238	3	32	theme	glycan	554:559	arg1	precursor					561:569	a truncated Man3GlcNAc2 glycan precursor	530:569	a truncated Man3GlcNAc2 glycan precursor	530:569	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	5	33	theme	complex-type	989:1000	arg1	glycans					1002:1008	digalactosylated complex-type glycans	972:1008	digalactosylated complex-type glycans	972:1008	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	3	34	theme	synthesis	629:637	arg1	pathway					639:645	a disrupted lipid-linked oligosaccharide synthesis pathway	588:645	a disrupted lipid-linked oligosaccharide synthesis pathway	588:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	4	35	theme	complex-type	675:686	arg1	N-glycans					704:712	galactosylated complex-type and hybrid-like N-glycans	660:712	galactosylated complex-type and hybrid-like N-glycans	660:712	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	10	36	theme	medium	1738:1743	arg1	supplementation					1745:1759	• Growth medium supplementation	1729:1759	• Growth medium supplementation	1729:1759	• Growth medium supplementation increases formation of target N-glycan structure.
34910238	8	37	theme	galactosylated	1621:1634	arg1	N-glycans					1636:1644	galactosylated N-glycans	1621:1644	galactosylated N-glycans	1621:1644	KEY POINTS: • Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.
34910238	3	38	theme	truncated	532:540	arg1	precursor					561:569	a truncated Man3GlcNAc2 glycan precursor	530:569	a truncated Man3GlcNAc2 glycan precursor	530:569	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	0	39	theme	N-glycans	42:50	arg1	Production					0:9	Production	0:9	Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae	0:94	Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae.
34910238	10	40	theme	N-glycan	1791:1798	arg1	structure					1800:1808	target N-glycan structure	1784:1808	target N-glycan structure	1784:1808	• Growth medium supplementation increases formation of target N-glycan structure.
34910238	0	41	theme	glycoengineered	55:69	arg1	cerevisiae					85:94	glycoengineered Saccharomyces cerevisiae	55:94	glycoengineered Saccharomyces cerevisiae	55:94	Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae.
34910238	7	42	theme	mannosylation	1493:1505	arg1	characterization					1457:1472	further characterization	1449:1472	further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain	1449:1554	Additionally, we provide further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain.
34910238	2	43	contain	carrying	273:280	arg2	glycosylation					299:311	human-compatible glycosylation	282:311	human-compatible glycosylation	282:311	Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts.
34910238	2	43	contain	carrying	273:280	arg1	proteins					264:271	proteins	264:271	proteins carrying human-compatible glycosylation	264:311	Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts.
34910238	3	44	theme	lipid-linked	600:611	arg1	oligosaccharide					613:627	a disrupted lipid-linked oligosaccharide	588:627	a disrupted lipid-linked oligosaccharide synthesis pathway	588:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	6	45	theme	transferases	1282:1293	arg1	expression					1255:1264	the expression	1251:1264	the expression of human GlcNAc transferases I and II	1251:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	4	46	theme	galactosyltransferase	736:756	arg1	protein					765:771	a human galactosyltransferase fusion protein	728:771	a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe	728:857	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	9	47	theme	•	1647:1647	arg1	constructs					1657:1666	• Genetic constructs	1647:1666	• Genetic constructs	1647:1666	• Genetic constructs impact the activities of the expressed glycosyltransferases.
34910238	6	48	theme	human	1269:1273	arg1	transferases					1282:1293	human GlcNAc transferases I and II	1269:1302	human GlcNAc transferases I and II	1269:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	48	theme	human	1269:1273	arg1	II					1301:1302	II	1301:1302	II	1301:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	48	theme	human	1269:1273	arg1	I					1295:1295	I	1295:1295	I	1295:1295	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	4	49	theme	hybrid-like	692:702	arg1	N-glycans					704:712	galactosylated complex-type and hybrid-like N-glycans	660:712	galactosylated complex-type and hybrid-like N-glycans	660:712	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	2	50	theme	proteins	353:360	arg1	production					327:336	the production	323:336	the production of therapeutic proteins in yeasts	323:370	Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts.
34910238	6	51	theme	growth	1346:1351	arg1	medium					1353:1358	the growth medium	1342:1358	the growth medium	1342:1358	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	4	52	theme	UDP-glucose	797:807	arg1	domain					821:826	a UDP-glucose 4-epimerase domain	795:826	a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe	795:857	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	9	53	theme	expressed	1697:1705	arg1	glycosyltransferases					1707:1726	the expressed glycosyltransferases	1693:1726	the expressed glycosyltransferases	1693:1726	• Genetic constructs impact the activities of the expressed glycosyltransferases.
34910238	5	54	theme	positive	1078:1085	arg1	impact					1087:1092	the positive impact	1074:1092	the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process	1074:1161	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	8	55	dep	POINTS	1561:1566	arg1	form					1616:1619	form	1616:1619	can form galactosylated N-glycans	1612:1644	KEY POINTS: • Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.
34910238	2	56	theme	human-compatible	282:297	arg1	glycosylation					299:311	human-compatible glycosylation	282:311	human-compatible glycosylation	282:311	Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts.
34910238	6	57	theme	glycans	1415:1421	arg1	formation					1374:1382	the formation	1370:1382	the formation of galactosylated complex-type glycans	1370:1421	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	58	theme	galactosylated	1387:1400	arg1	glycans					1415:1421	galactosylated complex-type glycans	1387:1421	galactosylated complex-type glycans	1387:1421	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	59	dep	galactosylated	1387:1400	arg1	complex-type					1402:1413	complex-type	1402:1413	complex-type	1402:1413	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	5	60	theme	glycans	1002:1008	arg1	production					958:967	the production	954:967	the production of digalactosylated complex-type glycans	954:1008	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	5	61	theme	4-epimerase	916:926	arg1	domain					928:933	the UDP-glucose 4-epimerase domain	900:933	the UDP-glucose 4-epimerase domain	900:933	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	1	62	theme	therapeutic	200:210	arg1	proteins					212:219	therapeutic proteins	200:219	therapeutic proteins	200:219	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	5	63	theme	galactosylation	1139:1153	arg1	process					1155:1161	the galactosylation process	1135:1161	the galactosylation process	1135:1161	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	8	64	theme	KEY	1557:1559	arg1	POINTS					1561:1566	KEY POINTS	1557:1566	KEY POINTS: • Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.	1557:1645	KEY POINTS: • Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.
34910238	3	65	dep	Saccharomyces	479:491	arg1	cerevisiae					493:502	cerevisiae	493:502	cerevisiae	493:502	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	5	66	theme	4-epimerase	1113:1123	arg1	domain					1125:1130	the UDP-glucose 4-epimerase domain	1097:1130	the UDP-glucose 4-epimerase domain	1097:1130	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	7	67	theme	glycoengineered	1527:1541	arg1	strain					1549:1554	the glycoengineered yeast strain	1523:1554	the glycoengineered yeast strain	1523:1554	Additionally, we provide further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain.
34910238	4	68	theme	galactosylated	660:673	arg1	N-glycans					704:712	galactosylated complex-type and hybrid-like N-glycans	660:712	galactosylated complex-type and hybrid-like N-glycans	660:712	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	8	69	theme	Glycoengineered	1571:1585	arg1	cerevisiae					1601:1610	• Glycoengineered Saccharomyces cerevisiae	1569:1610	• Glycoengineered Saccharomyces cerevisiae	1569:1610	KEY POINTS: • Glycoengineered Saccharomyces cerevisiae can form galactosylated N-glycans.
34910238	0	70	theme	complex-type	29:40	arg1	N-glycans					42:50	galactosylated complex-type N-glycans	14:50	galactosylated complex-type N-glycans	14:50	Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae.
34910238	1	71	theme	posttranslational	129:145	arg1	N-glycosylation					97:111	N-glycosylation	97:111	N-glycosylation	97:111	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	1	71	theme	posttranslational	129:145	arg1	modification					147:158	an important posttranslational modification	116:158	an important posttranslational modification affecting the properties and quality of therapeutic proteins	116:219	N-glycosylation is an important posttranslational modification affecting the properties and quality of therapeutic proteins.
34910238	3	72	theme	glycoengineering	448:463	arg1	strategy					465:472	a glycoengineering strategy	446:472	a glycoengineering strategy	446:472	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	2	73	from	production	327:336	arg1	yeasts					365:370	yeasts	365:370	yeasts	365:370	Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts.
34910238	3	74	theme	Δalg3	504:508	arg1	strain					517:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain	477:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway	477:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	10	75	theme	Growth	1731:1736	arg1	supplementation					1745:1759	• Growth medium supplementation	1729:1759	• Growth medium supplementation	1729:1759	• Growth medium supplementation increases formation of target N-glycan structure.
34910238	3	76	theme	Man3GlcNAc2	542:552	arg1	precursor					561:569	a truncated Man3GlcNAc2 glycan precursor	530:569	a truncated Man3GlcNAc2 glycan precursor	530:569	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	0	77	theme	Saccharomyces	71:83	arg1	cerevisiae					85:94	glycoengineered Saccharomyces cerevisiae	55:94	glycoengineered Saccharomyces cerevisiae	55:94	Production of galactosylated complex-type N-glycans in glycoengineered Saccharomyces cerevisiae.
34910238	5	78	theme	catalytic	1205:1213	arg1	activity					1215:1222	its catalytic activity	1201:1222	its catalytic activity	1201:1222	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	7	79	theme	interfering	1481:1491	arg1	mannosylation					1493:1505	the interfering mannosylation	1477:1505	the interfering mannosylation taking place in the glycoengineered yeast strain	1477:1554	Additionally, we provide further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain.
34910238	3	80	theme	Saccharomyces	479:491	arg1	strain					517:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain	477:522	a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway	477:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	10	81	theme	target	1784:1789	arg1	structure					1800:1808	target N-glycan structure	1784:1808	target N-glycan structure	1784:1808	• Growth medium supplementation increases formation of target N-glycan structure.
34910238	6	82	dep	transferases	1282:1293	arg1	transferases					1282:1293	human GlcNAc transferases I and II	1269:1302	human GlcNAc transferases I and II	1269:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	82	dep	transferases	1282:1293	arg1	II					1301:1302	II	1301:1302	II	1301:1302	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	82	dep	transferases	1282:1293	arg1	I					1295:1295	I	1295:1295	I	1295:1295	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	6	83	from	supplementation	1308:1322	arg1	medium					1353:1358	the growth medium	1342:1358	the growth medium	1342:1358	Moreover, optimization of the expression of human GlcNAc transferases I and II and supplementation of glucosamine in the growth medium increased the formation of galactosylated complex-type glycans.
34910238	4	84	theme	human	730:734	arg1	protein					765:771	a human galactosyltransferase fusion protein	728:771	a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe	728:857	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	2	85	from	Glycoengineering	222:237	arg1	yeast					242:246	yeast	242:246	yeast	242:246	Glycoengineering in yeast aims to produce proteins carrying human-compatible glycosylation, enabling the production of therapeutic proteins in yeasts.
34910238	5	86	theme	other	1180:1184	arg1	processes					1186:1194	other processes	1180:1194	other processes than its catalytic activity	1180:1222	Our results showed that the presence of the UDP-glucose 4-epimerase domain was beneficial for the production of digalactosylated complex-type glycans also when extracellular galactose was supplied, suggesting that the positive impact of the UDP-glucose 4-epimerase domain on the galactosylation process can be linked to other processes than its catalytic activity.
34910238	7	87	theme	further	1449:1455	arg1	characterization					1457:1472	further characterization	1449:1472	further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain	1449:1554	Additionally, we provide further characterization of the interfering mannosylation taking place in the glycoengineered yeast strain.
34910238	4	88	theme	fusion	758:763	arg1	protein					765:771	a human galactosyltransferase fusion protein	728:771	a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe	728:857	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
34910238	3	89	theme	oligosaccharide	613:627	arg1	pathway					639:645	a disrupted lipid-linked oligosaccharide synthesis pathway	588:645	a disrupted lipid-linked oligosaccharide synthesis pathway	588:645	In this work, we demonstrate further development and characterization of a glycoengineering strategy in a Saccharomyces cerevisiae Δalg3 Δalg11 strain where a truncated Man3GlcNAc2 glycan precursor is formed due to a disrupted lipid-linked oligosaccharide synthesis pathway.
34910238	4	90	from	pombe	853:857	arg1	domain					821:826	a UDP-glucose 4-epimerase domain	795:826	a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe	795:857	We produced galactosylated complex-type and hybrid-like N-glycans by expressing a human galactosyltransferase fusion protein both with and without a UDP-glucose 4-epimerase domain from Schizosaccharomyces pombe.
33135073	10	0	from	levels	1192:1197	arg1	patients					1209:1216	cancer patients	1202:1216	cancer patients	1202:1216	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	1	contain	containing	1485:1494	arg2	β1,6-branch					1511:1521	β1,6-branch	1511:1521	β1,6-branch	1511:1521	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	1	contain	containing	1485:1494	arg2	sialylation					1496:1506	sialylation	1496:1506	sialylation	1496:1506	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	1	contain	containing	1485:1494	arg1	free-N-glycans					1470:1483	free-N-glycans	1470:1483	α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)	1420:1576	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	2	dep	following	1231:1239	arg1	X					1295:1295	sialyl Lewis X	1282:1295	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	2	dep	following	1231:1239	arg1	glycans					1248:1254	small glycans	1242:1254	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	2	dep	following	1231:1239	arg1	glycans					1353:1359	lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans	1298:1359	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	11	3	theme	compounds	1703:1711	arg1	utility					1686:1692	the potential utility	1672:1692	the potential utility of these compounds as tumor markers	1672:1728	Our results provide further insight into urinary free-glycans and suggest the potential utility of these compounds as tumor markers.
33135073	10	4	dep	α1,3/4-fucose	1420:1432	arg1	+/-Fucα1-3					1566:1575	+/-Fucα1-3	1566:1575	+/-Fucα1-3	1566:1575	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	4	dep	α1,3/4-fucose	1420:1432	arg1	free-N-glycans					1470:1483	free-N-glycans	1470:1483	α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)	1420:1576	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	4	dep	α1,3/4-fucose	1420:1432	arg1	NeuAcα2-3Galβ1-4					1549:1564	novel NeuAcα2-3Galβ1-4	1543:1564	α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)	1420:1576	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	6	5	theme	high-performance	713:728	arg1	chromatography					737:750	high-performance liquid chromatography	713:750	high-performance liquid chromatography	713:750	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	8	6	attach	present	946:952	arg1	patients					983:990	cancer patients	976:990	cancer patients	976:990	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	6	attach	present	946:952	arg1	levels					966:971	elevated levels	957:971	elevated levels	957:971	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	6	attach	present	946:952	arg2	peaks					903:907	The chromatographic peaks	883:907	The chromatographic peaks suggested some of these glycans	883:939	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	6	attach	present	946:952	arg2	present					946:952	present	946:952	present	946:952	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	9	7	theme	cancer-associated	1003:1019	arg1	alterations					1021:1031	cancer-associated alterations	1003:1031	cancer-associated alterations	1003:1031	To verify cancer-associated alterations, we compared the glycan levels between cancer patients and normal controls by selected reaction monitoring.
33135073	4	8	with	controls	531:538	arg1	cancer					464:469	gastric cancer	456:469	gastric cancer	456:469	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	4	8	with	controls	531:538	arg1	cancer					483:488	pancreatic cancer	472:488	pancreatic cancer	472:488	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	4	8	with	controls	531:538	arg1	cholangiocarcinoma					494:511	cholangiocarcinoma	494:511	cholangiocarcinoma	494:511	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	11	9	theme	urinary	1639:1645	arg1	free-glycans					1647:1658	urinary free-glycans	1639:1658	urinary free-glycans	1639:1658	Our results provide further insight into urinary free-glycans and suggest the potential utility of these compounds as tumor markers.
33135073	10	10	dep	-extensions	1387:1397	arg1	II					1384:1385	II	1384:1385	II	1384:1385	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	11	with	glycans	1170:1176	arg1	levels					1192:1197	elevated levels	1183:1197	elevated levels in cancer patients	1183:1216	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	9	12	theme	glycan	1050:1055	arg1	levels					1057:1062	the glycan levels	1046:1062	the glycan levels between cancer patients and normal controls	1046:1106	To verify cancer-associated alterations, we compared the glycan levels between cancer patients and normal controls by selected reaction monitoring.
33135073	10	13	theme	sialyl	1282:1287	arg1	X					1295:1295	sialyl Lewis X	1282:1295	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	2	14	theme	protein	209:215	arg1	glycosylation					217:229	protein glycosylation	209:229	protein glycosylation	209:229	Most of these studies have focused on protein glycosylation but less attention has been paid to free-glycans.
33135073	0	15	from	alteration	56:65	arg1	cancer					70:75	cancer	70:75	cancer	70:75	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	0	15	from	alteration	56:65	arg1	urine					40:44	urine	40:44	urine	40:44	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	10	16	theme	lactose-	1298:1305	arg1	glycans					1353:1359	lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans	1298:1359	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	3	17	from	free-glycans	306:317	arg1	urine					326:330	the urine	322:330	the urine of cancer patients	322:349	Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates.
33135073	10	18	dep	glycans	1353:1359	arg1	type-I					1374:1379	type-I	1374:1379	type-I	1374:1379	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	18	dep	glycans	1353:1359	arg1	glycans					1589:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	4	19	theme	urine	408:412	arg1	samples					414:420	urine samples	408:420	urine samples	408:420	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	8	20	from	present	946:952	arg1	patients					983:990	cancer patients	976:990	cancer patients	976:990	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	9	21	theme	normal	1092:1097	arg1	controls					1099:1106	normal controls	1092:1106	normal controls	1092:1106	To verify cancer-associated alterations, we compared the glycan levels between cancer patients and normal controls by selected reaction monitoring.
33135073	8	22	theme	chromatographic	887:901	arg1	present					946:952	present	946:952	present	946:952	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	22	theme	chromatographic	887:901	arg1	peaks					903:907	The chromatographic peaks	883:907	The chromatographic peaks suggested some of these glycans	883:939	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	4	23	theme	pancreatic	472:481	arg1	cancer					483:488	pancreatic cancer	472:488	pancreatic cancer	472:488	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	10	24	theme	Lewis	1534:1538	arg1	X					1540:1540	6-sulfo Lewis X	1526:1540	6-sulfo Lewis X	1526:1540	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	1	25	theme	novel	147:151	arg1	biomarkers					159:168	novel tumor biomarkers	147:168	novel tumor biomarkers	147:168	Alterations to glycans in cancer patients have been used to identify novel tumor biomarkers.
33135073	0	26	from	Investigation	0:12	arg1	cancer					70:75	cancer	70:75	cancer	70:75	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	0	26	from	Investigation	0:12	arg1	urine					40:44	urine	40:44	urine	40:44	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	10	27	theme	N-acetyllactosamine	1311:1329	arg1	glycans					1353:1359	lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans	1298:1359	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	28	theme	elevated	1183:1190	arg1	levels					1192:1197	elevated levels	1183:1197	elevated levels in cancer patients	1183:1216	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	8	29	located	present	946:952	arg1	levels					966:971	elevated levels	957:971	elevated levels	957:971	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	29	located	present	946:952	arg1	patients					983:990	cancer patients	976:990	cancer patients	976:990	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	29	located	present	946:952	arg2	peaks					903:907	The chromatographic peaks	883:907	The chromatographic peaks suggested some of these glycans	883:939	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	29	located	present	946:952	arg2	present					946:952	present	946:952	present	946:952	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	6	30	theme	enzymatic	779:787	arg1	degradation					802:812	enzymatic and chemical degradation	779:812	enzymatic and chemical degradation	779:812	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	4	31	with	patients	442:449	arg1	cancer					464:469	gastric cancer	456:469	gastric cancer	456:469	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	4	31	with	patients	442:449	arg1	cancer					483:488	pancreatic cancer	472:488	pancreatic cancer	472:488	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	4	31	with	patients	442:449	arg1	cholangiocarcinoma					494:511	cholangiocarcinoma	494:511	cholangiocarcinoma	494:511	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	10	32	theme	glycans	1170:1176	arg1	structures					1156:1165	Representative structures	1141:1165	Representative structures of glycans with elevated levels in cancer patients	1141:1216	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	33	gly	sialylation	1496:1506	arg1	X					1540:1540	6-sulfo Lewis X	1526:1540	6-sulfo Lewis X	1526:1540	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	34	theme	type-II-core	1340:1351	arg1	glycans					1353:1359	lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans	1298:1359	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	7	35	theme	novel	848:852	arg1	structures					854:863	novel structures	848:863	novel structures	848:863	More than 100 glycans, including novel structures, were identified.
33135073	8	36	from	levels	966:971	arg1	present					946:952	present	946:952	present	946:952	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	36	from	levels	966:971	arg1	peaks					903:907	The chromatographic peaks	883:907	The chromatographic peaks suggested some of these glycans	883:939	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	3	37	theme	patients	342:349	arg1	urine					326:330	the urine	322:330	the urine of cancer patients	322:349	Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates.
33135073	10	38	theme	Xylα1-3Glc	1578:1587	arg1	glycans					1589:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	6	39	theme	free-glycans	697:708	arg1	profiling					676:684	profiling	676:684	profiling of urinary free-glycans	676:708	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	0	40	theme	acidic	17:22	arg1	free-glycans					24:35	acidic free-glycans	17:35	acidic free-glycans in urine	17:44	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	8	41	theme	elevated	957:964	arg1	levels					966:971	elevated levels	957:971	elevated levels	957:971	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	3	42	theme	tumor	369:373	arg1	candidates					382:391	novel tumor marker candidates	363:391	novel tumor marker candidates	363:391	Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates.
33135073	11	43	theme	potential	1676:1684	arg1	utility					1686:1692	the potential utility	1672:1692	the potential utility of these compounds as tumor markers	1672:1728	Our results provide further insight into urinary free-glycans and suggest the potential utility of these compounds as tumor markers.
33135073	10	44	from	Glc/GlcNAc	1458:1467	arg1	modifications					1403:1415	modifications	1403:1415	modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)	1403:1576	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	44	from	Glc/GlcNAc	1458:1467	arg1	-extensions					1387:1397	II)-extensions	1384:1397	II)-extensions	1384:1397	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	11	45	theme	tumor	1716:1720	arg1	markers					1722:1728	tumor markers	1716:1728	tumor markers	1716:1728	Our results provide further insight into urinary free-glycans and suggest the potential utility of these compounds as tumor markers.
33135073	6	46	theme	mass	756:759	arg1	spectrometry					761:772	mass spectrometry	756:772	mass spectrometry	756:772	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	10	47	theme	Lewis	1289:1293	arg1	X					1295:1295	sialyl Lewis X	1282:1295	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	6	48	with	spectrometry	761:772	arg1	degradation					802:812	enzymatic and chemical degradation	779:812	enzymatic and chemical degradation	779:812	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	11	49	theme	further	1618:1624	arg1	insight					1626:1632	further insight	1618:1632	further insight into urinary free-glycans	1618:1658	Our results provide further insight into urinary free-glycans and suggest the potential utility of these compounds as tumor markers.
33135073	1	50	theme	tumor	153:157	arg1	biomarkers					159:168	novel tumor biomarkers	147:168	novel tumor biomarkers	147:168	Alterations to glycans in cancer patients have been used to identify novel tumor biomarkers.
33135073	1	51	used	used	130:133	arg2	Alterations					78:88	Alterations	78:88	Alterations to glycans in cancer patients	78:118	Alterations to glycans in cancer patients have been used to identify novel tumor biomarkers.
33135073	6	52	theme	chemical	793:800	arg1	degradation					802:812	enzymatic and chemical degradation	779:812	enzymatic and chemical degradation	779:812	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	1	53	theme	cancer	104:109	arg1	patients					111:118	cancer patients	104:118	cancer patients	104:118	Alterations to glycans in cancer patients have been used to identify novel tumor biomarkers.
33135073	9	54	theme	cancer	1072:1077	arg1	patients					1079:1086	cancer patients	1072:1086	cancer patients	1072:1086	To verify cancer-associated alterations, we compared the glycan levels between cancer patients and normal controls by selected reaction monitoring.
33135073	9	55	theme	reaction	1120:1127	arg1	monitoring					1129:1138	selected reaction monitoring	1111:1138	selected reaction monitoring	1111:1138	To verify cancer-associated alterations, we compared the glycan levels between cancer patients and normal controls by selected reaction monitoring.
33135073	0	56	from	free-glycans	24:35	arg1	urine					40:44	urine	40:44	urine	40:44	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	10	57	theme	Representative	1141:1154	arg1	structures					1156:1165	Representative structures	1141:1165	Representative structures of glycans with elevated levels in cancer patients	1141:1216	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	58	with	glycans	1353:1359	arg1	LacNAc					1366:1371	LacNAc	1366:1371	LacNAc	1366:1371	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	3	59	theme	acidic	299:304	arg1	free-glycans					306:317	acidic free-glycans	299:317	acidic free-glycans in the urine of cancer patients	299:349	Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates.
33135073	10	60	theme	6-sulfo	1526:1532	arg1	X					1540:1540	6-sulfo Lewis X	1526:1540	6-sulfo Lewis X	1526:1540	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	9	61	theme	selected	1111:1118	arg1	monitoring					1129:1138	selected reaction monitoring	1111:1138	selected reaction monitoring	1111:1138	To verify cancer-associated alterations, we compared the glycan levels between cancer patients and normal controls by selected reaction monitoring.
33135073	3	62	theme	cancer	335:340	arg1	patients					342:349	cancer patients	335:349	cancer patients	335:349	Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates.
33135073	4	63	theme	gastric	456:462	arg1	cancer					464:469	gastric cancer	456:469	gastric cancer	456:469	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	8	64	from	patients	983:990	arg1	present					946:952	present	946:952	present	946:952	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	8	64	from	patients	983:990	arg1	peaks					903:907	The chromatographic peaks	883:907	The chromatographic peaks suggested some of these glycans	883:939	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	0	65	from	urine	40:44	arg1	Investigation					0:12	Investigation	0:12	Investigation of acidic free-glycans in urine	0:44	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	0	65	from	urine	40:44	arg1	alteration					56:65	their alteration	50:65	their alteration in cancer	50:75	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	10	66	theme	novel	1543:1547	arg1	+/-Fucα1-3					1566:1575	+/-Fucα1-3	1566:1575	+/-Fucα1-3	1566:1575	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	66	theme	novel	1543:1547	arg1	NeuAcα2-3Galβ1-4					1549:1564	novel NeuAcα2-3Galβ1-4	1543:1564	α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)	1420:1576	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	6	67	theme	liquid	730:735	arg1	chromatography					737:750	high-performance liquid chromatography	713:750	high-performance liquid chromatography	713:750	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	10	68	from	modifications	1403:1415	arg1	Glc/GlcNAc					1458:1467	the Glc/GlcNAc	1454:1467	the Glc/GlcNAc	1454:1467	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	3	69	theme	novel	363:367	arg1	candidates					382:391	novel tumor marker candidates	363:391	novel tumor marker candidates	363:391	Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates.
33135073	10	70	theme	X	1540:1540	arg1	β1,6-branch					1511:1521	β1,6-branch	1511:1521	β1,6-branch	1511:1521	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	70	theme	X	1540:1540	arg1	sialylation					1496:1506	sialylation	1496:1506	sialylation	1496:1506	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	0	71	theme	free-glycans	24:35	arg1	Investigation					0:12	Investigation	0:12	Investigation of acidic free-glycans in urine	0:44	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	0	71	theme	free-glycans	24:35	arg1	alteration					56:65	their alteration	50:65	their alteration in cancer	50:75	Investigation of acidic free-glycans in urine and their alteration in cancer.
33135073	10	72	theme	cancer	1202:1207	arg1	patients					1209:1216	cancer patients	1202:1216	cancer patients	1202:1216	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	5	73	theme	creatinine-adjusted	578:596	arg1	urine					598:602	creatinine-adjusted urine	578:602	creatinine-adjusted urine	578:602	The free-glycans were extracted from creatinine-adjusted urine and fluorescently labeled with 2-aminopyridine.
33135073	10	74	from	α1,3/4-fucose	1420:1432	arg1	Glc/GlcNAc					1458:1467	the Glc/GlcNAc	1454:1467	the Glc/GlcNAc	1454:1467	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	6	75	theme	urinary	689:695	arg1	free-glycans					697:708	urinary free-glycans	689:708	urinary free-glycans	689:708	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	10	76	from	-extensions	1387:1397	arg1	Glc/GlcNAc					1458:1467	the Glc/GlcNAc	1454:1467	the Glc/GlcNAc	1454:1467	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	6	77	with	chromatography	737:750	arg1	degradation					802:812	enzymatic and chemical degradation	779:812	enzymatic and chemical degradation	779:812	Initially, we performed profiling of urinary free-glycans by high-performance liquid chromatography and mass spectrometry with enzymatic and chemical degradation.
33135073	10	78	theme	modifications	1403:1415	arg1	glycans					1589:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	3	79	theme	marker	375:380	arg1	candidates					382:391	novel tumor marker candidates	363:391	novel tumor marker candidates	363:391	Here, we analyzed acidic free-glycans in the urine of cancer patients to identify novel tumor marker candidates.
33135073	4	80	theme	normal	524:529	arg1	controls					531:538	normal controls	524:538	patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls	442:538	Specifically, urine samples were collected from patients with gastric cancer, pancreatic cancer and cholangiocarcinoma as well as normal controls.
33135073	10	81	theme	-extensions	1387:1397	arg1	glycans					1589:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1384:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	1	82	from	glycans	93:99	arg1	patients					111:118	cancer patients	104:118	cancer patients	104:118	Alterations to glycans in cancer patients have been used to identify novel tumor biomarkers.
33135073	8	83	theme	cancer	976:981	arg1	patients					983:990	cancer patients	976:990	cancer patients	976:990	The chromatographic peaks suggested some of these glycans were present at elevated levels in cancer patients.
33135073	10	84	theme	6-sulfate	1441:1449	arg1	modifications					1403:1415	modifications	1403:1415	modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)	1403:1576	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	84	theme	6-sulfate	1441:1449	arg1	-extensions					1387:1397	II)-extensions	1384:1397	II)-extensions	1384:1397	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	85	theme	related	1256:1262	arg1	glycans					1248:1254	small glycans	1242:1254	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	86	theme	α1,3/4-fucose	1420:1432	arg1	modifications					1403:1415	modifications	1403:1415	modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)	1403:1576	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	86	theme	α1,3/4-fucose	1420:1432	arg1	-extensions					1387:1397	II)-extensions	1384:1397	II)-extensions	1384:1397	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
33135073	10	87	theme	small	1242:1246	arg1	glycans					1248:1254	small glycans	1242:1254	the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans	1227:1595	Representative structures of glycans with elevated levels in cancer patients included the following: small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3) Xylα1-3Glc glycans.
34200965	9	0	theme	N-glycosylation	1356:1370	arg1	modulator					1343:1351	2-deoxy-glucose-a modulator	1325:1351	2-deoxy-glucose-a modulator of N-glycosylation	1325:1370	The methodology was established using the colon cancer cell line CX1, which was treated with 2-deoxy-glucose-a modulator of N-glycosylation.
34200965	3	1	theme	membrane	399:406	arg1	proteins					408:415	membrane proteins	399:415	membrane proteins	399:415	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	4	2	theme	cellular	558:565	arg1	target					622:627	a therapeutic target	608:627	a therapeutic target	608:627	The cellular glycome is increasingly considered to be a therapeutic target.
34200965	4	2	theme	cellular	558:565	arg1	glycome					567:573	The cellular glycome	554:573	The cellular glycome	554:573	The cellular glycome is increasingly considered to be a therapeutic target.
34200965	8	3	theme	mass	1150:1153	arg1	spectrometry					1155:1166	nanoUPLC-coupled mass spectrometry	1133:1166	nanoUPLC-coupled mass spectrometry	1133:1166	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry identified the altered glycoproteins and respective glycosites.
34200965	5	4	theme	new	649:651	arg1	strategy					653:660	a new strategy	647:660	a new strategy to compare membrane glycoproteomes	647:695	Here we describe a new strategy to compare membrane glycoproteomes, thereby identifying proteins with altered glycan structures and the respective glycosites.
34200965	7	5	theme	glycan	959:964	arg1	part					966:969	the glycan part	955:969	the glycan part of a glycopeptide	955:987	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	2	6	theme	Protein	185:191	arg1	glycosylation					193:205	Protein glycosylation	185:205	Protein glycosylation	185:205	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	8	7	theme	nanoUPLC-coupled	1133:1148	arg1	spectrometry					1155:1166	nanoUPLC-coupled mass spectrometry	1133:1166	nanoUPLC-coupled mass spectrometry	1133:1166	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry identified the altered glycoproteins and respective glycosites.
34200965	7	8	theme	exclusion	1029:1037	arg1	chromatography					1039:1052	analytical size exclusion chromatography	1013:1052	analytical size exclusion chromatography	1013:1052	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	2	9	theme	receptor	325:332	arg1	activation					334:343	receptor activation	325:343	receptor activation	325:343	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	8	10	gly	glycoproteins	1191:1203	arg1	glycoproteins					1191:1203	the altered glycoproteins	1179:1203	the altered glycoproteins	1179:1203	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry identified the altered glycoproteins and respective glycosites.
34200965	3	11	theme	various	526:532	arg1	mechanisms					542:551	various disease mechanisms	526:551	various disease mechanisms	526:551	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	1	12	theme	varied	128:133	arg1	Glycosylation					88:100	Glycosylation	88:100	Glycosylation	88:100	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
34200965	1	12	theme	varied	128:133	arg1	form					135:138	the most prevalent and varied form	105:138	the most prevalent and varied form of post-translational protein modifications	105:182	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
34200965	3	13	gly	glycosylated	439:450	arg2	proteins					408:415	membrane proteins	399:415	membrane proteins	399:415	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	3	13	gly	glycosylated	439:450	arg1	particular					387:396	particular	387:396	particular	387:396	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	3	13	gly	glycosylated	439:450	arg1	proteins					408:415	membrane proteins	399:415	membrane proteins	399:415	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	6	14	theme	proteins	868:875	arg1	digestion					846:854	the digestion	842:854	the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides	842:931	The workflow started with an optimized procedure for the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides.
34200965	6	15	gly	glycopeptides	919:931	arg2	glycopeptides					919:931	glycopeptides	919:931	glycopeptides	919:931	The workflow started with an optimized procedure for the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides.
34200965	3	16	theme	physiological	477:489	arg1	processes					491:499	physiological processes	477:499	physiological processes	477:499	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	5	17	theme	membrane	673:680	arg1	glycoproteomes					682:695	membrane glycoproteomes	673:695	membrane glycoproteomes	673:695	Here we describe a new strategy to compare membrane glycoproteomes, thereby identifying proteins with altered glycan structures and the respective glycosites.
34200965	6	18	theme	membrane	859:866	arg1	proteins					868:875	membrane proteins	859:875	membrane proteins	859:875	The workflow started with an optimized procedure for the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides.
34200965	10	19	theme	cell	1420:1423	arg1	culture					1425:1431	cell culture	1420:1431	cell culture	1420:1431	The described methodology is not restricted to cell culture, as it can also be adapted to tissue samples or body fluids.
34200965	11	20	theme	various	1531:1537	arg1	settings					1552:1559	various experimental settings	1531:1559	various experimental settings	1531:1559	Altogether, it is a useful module in various experimental settings that target glycan functions.
34200965	0	21	theme	Glycosite	13:21	arg1	Method					45:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method to Compare Membrane Glycoproteomes.
34200965	8	22	theme	altered	1183:1189	arg1	glycoproteins					1191:1203	the altered glycoproteins	1179:1203	the altered glycoproteins	1179:1203	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry identified the altered glycoproteins and respective glycosites.
34200965	7	23	theme	size	1024:1027	arg1	chromatography					1039:1052	analytical size exclusion chromatography	1013:1052	analytical size exclusion chromatography	1013:1052	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	8	24	gly	glycosites	1220:1229	arg2	glycosites					1220:1229	respective glycosites	1209:1229	respective glycosites	1209:1229	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry identified the altered glycoproteins and respective glycosites.
34200965	0	25	theme	Differential	0:11	arg1	Method					45:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method to Compare Membrane Glycoproteomes.
34200965	3	26	dep	both	462:465	arg1	linked					467:472	linked	467:472	linked to physiological processes	467:499	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	10	27	theme	body	1481:1484	arg1	fluids					1486:1491	body fluids	1481:1491	body fluids	1481:1491	The described methodology is not restricted to cell culture, as it can also be adapted to tissue samples or body fluids.
34200965	6	28	theme	glycopeptides	919:931	arg1	isolation					906:914	the lectin-based isolation	889:914	the lectin-based isolation of glycopeptides	889:931	The workflow started with an optimized procedure for the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides.
34200965	11	29	theme	experimental	1539:1550	arg1	settings					1552:1559	various experimental settings	1531:1559	various experimental settings	1531:1559	Altogether, it is a useful module in various experimental settings that target glycan functions.
34200965	0	30	theme	Versatile	35:43	arg1	Method					45:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method to Compare Membrane Glycoproteomes.
34200965	7	31	from	alterations	940:950	arg1	part					966:969	the glycan part	955:969	the glycan part of a glycopeptide	955:987	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	8	32	theme	N-glycosidase	1095:1107	arg1	treatment					1109:1117	N-glycosidase treatment	1095:1117	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry	1095:1166	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry identified the altered glycoproteins and respective glycosites.
34200965	2	33	theme	signal	346:351	arg1	transduction					353:364	signal transduction	346:364	signal transduction	346:364	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	3	34	theme	high	508:511	arg1	relevance					513:521	high relevance	508:521	high relevance in various disease mechanisms	508:551	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	0	35	theme	Profiling-A	23:33	arg1	Method					45:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method	0:50	Differential Glycosite Profiling-A Versatile Method to Compare Membrane Glycoproteomes.
34200965	5	36	theme	respective	766:775	arg1	glycosites					777:786	the respective glycosites	762:786	the respective glycosites	762:786	Here we describe a new strategy to compare membrane glycoproteomes, thereby identifying proteins with altered glycan structures and the respective glycosites.
34200965	2	37	theme	cellular	226:233	arg1	folding					264:270	protein folding	256:270	protein folding	256:270	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	37	theme	cellular	226:233	arg1	transduction					353:364	signal transduction	346:364	signal transduction	346:364	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	37	theme	cellular	226:233	arg1	adhesion					278:285	cell adhesion	273:285	cell adhesion	273:285	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	37	theme	cellular	226:233	arg1	functions					235:243	multiple cellular functions	217:243	multiple cellular functions	217:243	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	37	theme	cellular	226:233	arg1	activation					334:343	receptor activation	325:343	receptor activation	325:343	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	37	theme	cellular	226:233	arg1	endocytosis					371:381	endocytosis	371:381	endocytosis	371:381	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	37	theme	cellular	226:233	arg1	trafficking					298:308	molecular trafficking	288:308	molecular trafficking	288:308	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	5	38	gly	glycosites	777:786	arg2	glycosites					777:786	the respective glycosites	762:786	the respective glycosites	762:786	Here we describe a new strategy to compare membrane glycoproteomes, thereby identifying proteins with altered glycan structures and the respective glycosites.
34200965	11	39	theme	glycan	1573:1578	arg1	functions					1580:1588	glycan functions	1573:1588	glycan functions	1573:1588	Altogether, it is a useful module in various experimental settings that target glycan functions.
34200965	4	40	theme	therapeutic	610:620	arg1	glycome					567:573	The cellular glycome	554:573	The cellular glycome	554:573	The cellular glycome is increasingly considered to be a therapeutic target.
34200965	4	40	theme	therapeutic	610:620	arg1	target					622:627	a therapeutic target	608:627	a therapeutic target	608:627	The cellular glycome is increasingly considered to be a therapeutic target.
34200965	2	41	theme	multiple	217:224	arg1	folding					264:270	protein folding	256:270	protein folding	256:270	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	41	theme	multiple	217:224	arg1	transduction					353:364	signal transduction	346:364	signal transduction	346:364	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	41	theme	multiple	217:224	arg1	adhesion					278:285	cell adhesion	273:285	cell adhesion	273:285	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	41	theme	multiple	217:224	arg1	functions					235:243	multiple cellular functions	217:243	multiple cellular functions	217:243	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	41	theme	multiple	217:224	arg1	activation					334:343	receptor activation	325:343	receptor activation	325:343	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	41	theme	multiple	217:224	arg1	endocytosis					371:381	endocytosis	371:381	endocytosis	371:381	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	2	41	theme	multiple	217:224	arg1	trafficking					298:308	molecular trafficking	288:308	molecular trafficking	288:308	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	7	42	theme	glycopeptide	976:987	arg1	part					966:969	the glycan part	955:969	the glycan part of a glycopeptide	955:987	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	8	43	theme	respective	1209:1218	arg1	glycosites					1220:1229	respective glycosites	1209:1229	respective glycosites	1209:1229	N-glycosidase treatment combined with nanoUPLC-coupled mass spectrometry identified the altered glycoproteins and respective glycosites.
34200965	2	44	theme	cell	273:276	arg1	adhesion					278:285	cell adhesion	273:285	cell adhesion	273:285	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	10	45	theme	tissue	1463:1468	arg1	samples					1470:1476	tissue samples	1463:1476	tissue samples	1463:1476	The described methodology is not restricted to cell culture, as it can also be adapted to tissue samples or body fluids.
34200965	9	46	theme	cell	1287:1290	arg1	line					1292:1295	the colon cancer cell line CX1	1270:1299	the colon cancer cell line CX1	1270:1299	The methodology was established using the colon cancer cell line CX1, which was treated with 2-deoxy-glucose-a modulator of N-glycosylation.
34200965	0	47	theme	Membrane	63:70	arg1	Glycoproteomes					72:85	Membrane Glycoproteomes	63:85	Membrane Glycoproteomes	63:85	Differential Glycosite Profiling-A Versatile Method to Compare Membrane Glycoproteomes.
34200965	11	48	theme	useful	1514:1519	arg1	it					1506:1507	it	1506:1507	it	1506:1507	Altogether, it is a useful module in various experimental settings that target glycan functions.
34200965	11	48	theme	useful	1514:1519	arg1	module					1521:1526	a useful module	1512:1526	a useful module in various experimental settings that target glycan functions	1512:1588	Altogether, it is a useful module in various experimental settings that target glycan functions.
34200965	5	49	theme	altered	732:738	arg1	structures					747:756	altered glycan structures	732:756	altered glycan structures	732:756	Here we describe a new strategy to compare membrane glycoproteomes, thereby identifying proteins with altered glycan structures and the respective glycosites.
34200965	11	50	from	module	1521:1526	arg1	settings					1552:1559	various experimental settings	1531:1559	various experimental settings	1531:1559	Altogether, it is a useful module in various experimental settings that target glycan functions.
34200965	3	51	theme	disease	534:540	arg1	mechanisms					542:551	various disease mechanisms	526:551	various disease mechanisms	526:551	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	5	52	theme	glycan	740:745	arg1	structures					747:756	altered glycan structures	732:756	altered glycan structures	732:756	Here we describe a new strategy to compare membrane glycoproteomes, thereby identifying proteins with altered glycan structures and the respective glycosites.
34200965	2	53	theme	protein	256:262	arg1	folding					264:270	protein folding	256:270	protein folding	256:270	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	6	54	theme	optimized	818:826	arg1	procedure					828:836	an optimized procedure	815:836	an optimized procedure for the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides	815:931	The workflow started with an optimized procedure for the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides.
34200965	10	55	theme	described	1377:1385	arg1	methodology					1387:1397	The described methodology	1373:1397	The described methodology	1373:1397	The described methodology is not restricted to cell culture, as it can also be adapted to tissue samples or body fluids.
34200965	10	55	theme	described	1377:1385	arg1	restricted					1406:1415	restricted	1406:1415	restricted	1406:1415	The described methodology is not restricted to cell culture, as it can also be adapted to tissue samples or body fluids.
34200965	7	56	theme	analytical	1013:1022	arg1	chromatography					1039:1052	analytical size exclusion chromatography	1013:1052	analytical size exclusion chromatography	1013:1052	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	3	57	from	relevance	513:521	arg1	mechanisms					542:551	various disease mechanisms	526:551	various disease mechanisms	526:551	In particular, membrane proteins are frequently highly glycosylated, which is both linked to physiological processes and of high relevance in various disease mechanisms.
34200965	1	58	theme	prevalent	114:122	arg1	Glycosylation					88:100	Glycosylation	88:100	Glycosylation	88:100	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
34200965	1	58	theme	prevalent	114:122	arg1	form					135:138	the most prevalent and varied form	105:138	the most prevalent and varied form of post-translational protein modifications	105:182	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
34200965	9	59	theme	colon	1274:1278	arg1	line					1292:1295	the colon cancer cell line CX1	1270:1299	the colon cancer cell line CX1	1270:1299	The methodology was established using the colon cancer cell line CX1, which was treated with 2-deoxy-glucose-a modulator of N-glycosylation.
34200965	7	60	gly	glycopeptide	976:987	arg2	glycopeptide					976:987	a glycopeptide	974:987	a glycopeptide	974:987	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	9	61	theme	cancer	1280:1285	arg1	line					1292:1295	the colon cancer cell line CX1	1270:1299	the colon cancer cell line CX1	1270:1299	The methodology was established using the colon cancer cell line CX1, which was treated with 2-deoxy-glucose-a modulator of N-glycosylation.
34200965	1	62	theme	post-translational	143:160	arg1	modifications					170:182	post-translational protein modifications	143:182	post-translational protein modifications	143:182	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
34200965	6	63	theme	lectin-based	893:904	arg1	isolation					906:914	the lectin-based isolation	889:914	the lectin-based isolation of glycopeptides	889:931	The workflow started with an optimized procedure for the digestion of membrane proteins followed by the lectin-based isolation of glycopeptides.
34200965	2	64	theme	molecular	288:296	arg1	trafficking					298:308	molecular trafficking	288:308	molecular trafficking	288:308	Protein glycosylation regulates multiple cellular functions, including protein folding, cell adhesion, molecular trafficking and clearance, receptor activation, signal transduction, and endocytosis.
34200965	7	65	theme	mass	1082:1085	arg1	shifts					1087:1092	these mass shifts	1076:1092	these mass shifts	1076:1092	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	1	66	theme	protein	162:168	arg1	modifications					170:182	post-translational protein modifications	143:182	post-translational protein modifications	143:182	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
34200965	7	67	theme	mass	995:998	arg1	alterations					1000:1010	mass alterations	995:1010	mass alterations	995:1010	Since alterations in the glycan part of a glycopeptide cause mass alterations, analytical size exclusion chromatography was applied to detect these mass shifts.
34200965	9	68	theme	2-deoxy-glucose-a	1325:1341	arg1	modulator					1343:1351	2-deoxy-glucose-a modulator	1325:1351	2-deoxy-glucose-a modulator of N-glycosylation	1325:1370	The methodology was established using the colon cancer cell line CX1, which was treated with 2-deoxy-glucose-a modulator of N-glycosylation.
34200965	1	69	theme	modifications	170:182	arg1	Glycosylation					88:100	Glycosylation	88:100	Glycosylation	88:100	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
34200965	1	69	theme	modifications	170:182	arg1	form					135:138	the most prevalent and varied form	105:138	the most prevalent and varied form of post-translational protein modifications	105:182	Glycosylation is the most prevalent and varied form of post-translational protein modifications.
33093196	7	0	theme	connected	1279:1287	arg1	clusters					1296:1303	highly connected glycan clusters	1272:1303	highly connected glycan clusters	1272:1303	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	2	1	theme	integrated	303:312	arg1	approach					314:321	an integrated approach	300:321	an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels	300:505	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	7	2	theme	glycan	1289:1294	arg1	clusters					1296:1303	highly connected glycan clusters	1272:1303	highly connected glycan clusters	1272:1303	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	6	3	from	changes	1060:1066	arg1	shield					1082:1087	shield	1082:1087	shield	1082:1087	Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production.
33093196	4	4	theme	protein	734:740	arg1	surface					742:748	buried and exposed protein surface	715:748	buried and exposed protein surface	715:748	This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env.
33093196	4	5	theme	buried	715:720	arg1	surface					742:748	buried and exposed protein surface	715:748	buried and exposed protein surface	715:748	This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env.
33093196	1	6	theme	immunogenicity	192:205	arg1	array					70:74	The dense array	60:74	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield,"	60:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	6	theme	immunogenicity	192:205	arg1	determinant					177:187	a key determinant	171:187	a key determinant of immunogenicity	171:205	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	6	7	theme	same	1128:1131	arg1	line					1138:1141	the same cell line	1124:1141	the same cell line used for vaccine production	1124:1169	Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production.
33093196	7	8	theme	immune	1422:1427	arg1	evasion					1429:1435	immune evasion	1422:1435	immune evasion	1422:1435	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	1	9	from	glycoprotein	118:129	arg1	determinant					177:187	a key determinant	171:187	a key determinant of immunogenicity	171:205	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	9	from	glycoprotein	118:129	arg1	array					70:74	The dense array	60:74	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield,"	60:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	4	10	theme	exposed	726:732	arg1	surface					742:748	buried and exposed protein surface	715:748	buried and exposed protein surface	715:748	This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env.
33093196	5	11	theme	subtle	895:900	arg1	changes					902:908	subtle changes	895:908	subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility	895:1017	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	5	12	from	changes	902:908	arg1	composition					931:941	composition	931:941	composition	931:941	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	5	12	from	changes	902:908	arg1	dynamics					948:955	dynamics	948:955	dynamics	948:955	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	5	12	from	changes	902:908	arg1	occupancy					920:928	glycan occupancy	913:928	glycan occupancy	913:928	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	5	13	theme	Env	825:827	arg1	Analysis					813:820	Analysis	813:820	Analysis of Env expressed in different cell lines	813:861	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	2	14	theme	shield	458:463	arg1	structure					465:473	glycan shield structure	451:473	glycan shield structure	451:473	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	6	15	theme	Env	1092:1094	arg1	shield					1082:1087	shield	1082:1087	shield	1082:1087	Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production.
33093196	1	16	theme	dense	64:68	arg1	determinant					177:187	a key determinant	171:187	a key determinant of immunogenicity	171:205	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	16	theme	dense	64:68	arg1	array					70:74	The dense array	60:74	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield,"	60:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	2	17	theme	cryomicroscopy	351:364	arg1	approach					314:321	an integrated approach	300:321	an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels	300:505	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	2	18	theme	site-specific	405:417	arg1	spectrometry					424:435	site-specific mass spectrometry	405:435	site-specific mass spectrometry (MS)	405:440	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	2	18	theme	site-specific	405:417	arg1	MS					438:439	MS	438:439	MS	438:439	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	1	19	link	N-linked	79:86	arg1	glycans					88:94	N-linked glycans	79:94	N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield,"	79:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	5	20	theme	glycan	913:918	arg1	occupancy					920:928	glycan occupancy	913:928	glycan occupancy	913:928	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	2	21	theme	electron	342:349	arg1	cryomicroscopy					351:364	single-particle electron cryomicroscopy	326:364	single-particle electron cryomicroscopy (cryo-EM)	326:374	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	2	21	theme	electron	342:349	arg1	cryo-EM					367:373	cryo-EM	367:373	cryo-EM	367:373	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	7	22	gly	deglycosylation	1208:1222	arg1	Env					1227:1229	Env	1227:1229	Env	1227:1229	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	7	22	gly	deglycosylation	1208:1222	arg1	manner					1250:1255	a time-resolved manner	1234:1255	a time-resolved manner	1234:1255	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	2	23	theme	single-particle	326:340	arg1	cryomicroscopy					351:364	single-particle electron cryomicroscopy	326:364	single-particle electron cryomicroscopy (cryo-EM)	326:374	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	2	23	theme	single-particle	326:340	arg1	cryo-EM					367:373	cryo-EM	367:373	cryo-EM	367:373	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	0	24	theme	HIV-1	21:25	arg1	glycan					31:36	the HIV-1 Env glycan	17:36	the HIV-1 Env glycan	17:36	Visualization of the HIV-1 Env glycan shield across scales.
33093196	1	25	theme	intrinsic	212:220	arg1	heterogeneity					222:234	intrinsic heterogeneity	212:234	intrinsic heterogeneity	212:234	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	5	26	theme	epitope	997:1003	arg1	accessibility					1005:1017	epitope accessibility	997:1017	epitope accessibility	997:1017	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	1	27	theme	N-linked	79:86	arg1	glycans					88:94	N-linked glycans	79:94	N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield,"	79:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	5	28	theme	shield	976:981	arg1	structure					983:991	impact glycan shield structure	962:991	impact glycan shield structure	962:991	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	2	29	theme	computational	377:389	arg1	modeling					391:398	computational modeling	377:398	computational modeling	377:398	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	2	30	theme	modeling	391:398	arg1	approach					314:321	an integrated approach	300:321	an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels	300:505	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	6	31	from	expression	1110:1119	arg1	line					1138:1141	the same cell line	1124:1141	the same cell line used for vaccine production	1124:1169	Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production.
33093196	1	32	theme	glycans	88:94	arg1	determinant					177:187	a key determinant	171:187	a key determinant of immunogenicity	171:205	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	32	theme	glycans	88:94	arg1	array					70:74	The dense array	60:74	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield,"	60:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	0	33	theme	glycan	31:36	arg1	Visualization					0:12	Visualization	0:12	Visualization of the HIV-1 Env glycan	0:36	Visualization of the HIV-1 Env glycan shield across scales.
33093196	2	34	theme	multiple	491:498	arg1	levels					500:505	multiple levels	491:505	multiple levels	491:505	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	4	35	theme	immunogenic	787:797	arg1	sites					799:803	potentially immunogenic sites	775:803	potentially immunogenic sites	775:803	This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env.
33093196	5	36	theme	different	842:850	arg1	lines					857:861	different cell lines	842:861	different cell lines	842:861	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	1	37	theme	shield	159:164	arg1	"					166:166	the "glycan shield,"	147:166	"	166:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	0	38	theme	Env	27:29	arg1	glycan					31:36	the HIV-1 Env glycan	17:36	the HIV-1 Env glycan	17:36	Visualization of the HIV-1 Env glycan shield across scales.
33093196	1	39	theme	typical	246:252	arg1	analysis					273:280	typical structure-function analysis	246:280	typical structure-function analysis	246:280	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	7	40	theme	prefusion	1355:1363	arg1	trimer					1365:1370	the prefusion trimer	1351:1370	the prefusion trimer	1351:1370	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	3	41	theme	extensive	542:550	arg1	network					552:558	an extensive network	539:558	an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield	539:662	We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield.
33093196	2	42	theme	spectrometry	424:435	arg1	approach					314:321	an integrated approach	300:321	an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels	300:505	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	1	43	theme	structure-function	254:271	arg1	analysis					273:280	typical structure-function analysis	246:280	typical structure-function analysis	246:280	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	3	44	dep	glycan	650:655	arg1	shield					657:662	shield	657:662	shield	657:662	We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield.
33093196	7	45	theme	time-resolved	1236:1248	arg1	manner					1250:1255	a time-resolved manner	1234:1255	a time-resolved manner	1234:1255	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	2	46	theme	mass	419:422	arg1	spectrometry					424:435	site-specific mass spectrometry	405:435	site-specific mass spectrometry (MS)	405:440	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	2	46	theme	mass	419:422	arg1	MS					438:439	MS	438:439	MS	438:439	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	1	47	gly	glycoprotein	118:129	arg1	Env					132:134	Env	132:134	Env	132:134	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	47	gly	glycoprotein	118:129	arg1	glycoprotein					118:129	the HIV-1 envelope glycoprotein	99:129	the HIV-1 envelope glycoprotein (Env)	99:135	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	3	48	theme	structure	629:637	arg1	formation					603:611	the formation	599:611	the formation of higher-order structure within the glycan shield	599:662	We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield.
33093196	4	49	theme	sites	799:803	arg1	mapping					764:770	a mapping	762:770	a mapping of potentially immunogenic sites on Env	762:810	This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env.
33093196	7	50	dep	glycan	1388:1393	arg1	shield					1395:1400	shield	1395:1400	shield	1395:1400	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	6	51	theme	vaccine	1152:1158	arg1	production					1160:1169	vaccine production	1152:1169	vaccine production	1152:1169	Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production.
33093196	3	52	theme	interglycan	563:573	arg1	interactions					575:586	interglycan interactions	563:586	interglycan interactions that drive the formation of higher-order structure within the glycan shield	563:662	We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield.
33093196	1	53	theme	HIV-1	103:107	arg1	Env					132:134	Env	132:134	Env	132:134	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	53	theme	HIV-1	103:107	arg1	glycoprotein					118:129	the HIV-1 envelope glycoprotein	99:129	the HIV-1 envelope glycoprotein (Env)	99:135	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	54	from	glycans	88:94	arg1	Env					132:134	Env	132:134	Env	132:134	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	54	from	glycans	88:94	arg1	glycoprotein					118:129	the HIV-1 envelope glycoprotein	99:129	the HIV-1 envelope glycoprotein (Env)	99:135	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	6	55	theme	cell	1133:1136	arg1	line					1138:1141	the same cell line	1124:1141	the same cell line used for vaccine production	1124:1169	Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production.
33093196	3	56	theme	interactions	575:586	arg1	network					552:558	an extensive network	539:558	an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield	539:662	We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield.
33093196	1	57	theme	envelope	109:116	arg1	Env					132:134	Env	132:134	Env	132:134	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	57	theme	envelope	109:116	arg1	glycoprotein					118:129	the HIV-1 envelope glycoprotein	99:129	the HIV-1 envelope glycoprotein (Env)	99:135	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	58	from	array	70:74	arg1	Env					132:134	Env	132:134	Env	132:134	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	58	from	array	70:74	arg1	glycoprotein					118:129	the HIV-1 envelope glycoprotein	99:129	the HIV-1 envelope glycoprotein (Env)	99:135	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	4	59	theme	diffuse	688:694	arg1	boundaries					696:705	diffuse boundaries	688:705	diffuse boundaries between buried and exposed protein surface	688:748	This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env.
33093196	2	60	theme	glycan	451:456	arg1	structure					465:473	glycan shield structure	451:473	glycan shield structure	451:473	Here, we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass spectrometry (MS) to probe glycan shield structure and behavior at multiple levels.
33093196	3	61	theme	higher-order	616:627	arg1	structure					629:637	higher-order structure	616:637	higher-order structure	616:637	We found that dynamics lead to an extensive network of interglycan interactions that drive the formation of higher-order structure within the glycan shield.
33093196	5	62	theme	impact	962:967	arg1	structure					983:991	impact glycan shield structure	962:991	impact glycan shield structure	962:991	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	4	63	from	mapping	764:770	arg1	Env					808:810	Env	808:810	Env	808:810	This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env.
33093196	5	64	theme	cell	852:855	arg1	lines					857:861	different cell lines	842:861	different cell lines	842:861	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	6	65	theme	unforeseen	1049:1058	arg1	changes					1060:1066	unforeseen changes	1049:1066	unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production	1049:1169	Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same cell line used for vaccine production.
33093196	5	66	theme	glycan	969:974	arg1	structure					983:991	impact glycan shield structure	962:991	impact glycan shield structure	962:991	Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility.
33093196	7	67	theme	Env	1227:1229	arg1	deglycosylation					1208:1222	the enzymatic deglycosylation	1194:1222	the enzymatic deglycosylation of Env	1194:1229	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	7	68	theme	enzymatic	1198:1206	arg1	deglycosylation					1208:1222	the enzymatic deglycosylation	1194:1222	the enzymatic deglycosylation of Env	1194:1229	Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner, we found that highly connected glycan clusters are resistant to digestion and help stabilize the prefusion trimer, suggesting the glycan shield may function beyond immune evasion.
33093196	1	69	theme	key	173:175	arg1	array					70:74	The dense array	60:74	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield,"	60:166	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33093196	1	69	theme	key	173:175	arg1	determinant					177:187	a key determinant	171:187	a key determinant of immunogenicity	171:205	The dense array of N-linked glycans on the HIV-1 envelope glycoprotein (Env), known as the "glycan shield," is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis.
33993882	6	0	theme	intrastriatal	968:980	arg1	METHODS					930:936	METHODS	930:936	METHODS With that aim	930:950	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	0	theme	intrastriatal	968:980	arg1	model					1057:1061	a model	1055:1061	a model of neuroinflammation	1055:1082	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	0	theme	intrastriatal	968:980	arg1	injection					982:990	the unilateral intrastriatal injection	953:990	the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain	953:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	7	1	theme	N-glycome	1182:1190	arg1	characterisation					1135:1150	In vivo and post-mortem, quantitative and spatial characterisation	1085:1150	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome	1085:1190	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS.
33993882	10	2	theme	high-resolution	1879:1893	arg1	distribution					1903:1914	a high-resolution spatial distribution	1877:1914	a high-resolution spatial distribution of N-glycans	1877:1927	This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres.
33993882	2	3	dep	addition	368:375	arg1	i.e.					343:346	i.e.	343:346	i.e.	343:346	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	6	4	used	used	1047:1050	arg2	METHODS					930:936	METHODS	930:936	METHODS With that aim	930:950	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	4	used	used	1047:1050	arg2	injection					982:990	the unilateral intrastriatal injection	953:990	the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain	953:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	4	used	used	1047:1050	arg2	model					1057:1061	a model	1055:1061	a model of neuroinflammation	1055:1082	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	3	5	theme	glycosylation	560:572	arg1	diseases					574:581	congenital glycosylation diseases	549:581	congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation	549:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	12	6	theme	pioneering	2187:2196	arg1	step					2198:2201	a pioneering step	2185:2201	a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases	2185:2296	These data represent a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases.
33993882	3	7	with	type	445:448	arg1	role					483:486	a cardinal role	472:486	a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation	472:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	11	8	from	profiling	2073:2081	arg1	model					2136:2140	a well-characterised animal model	2108:2140	a well-characterised animal model of neuroinflammation	2108:2161	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	9	9	theme	oligomannose	1768:1779	arg1	N-glycans					1781:1789	oligomannose N-glycans	1768:1789	oligomannose N-glycans	1768:1789	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	7	10	theme	LPS	1234:1236	arg1	post-injection					1216:1229	1-week post-injection	1209:1229	1-week post-injection of LPS	1209:1236	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS.
33993882	8	11	theme	emission	1321:1328	arg1	PET					1342:1344	PET	1342:1344	PET	1342:1344	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	8	11	theme	emission	1321:1328	arg1	tomography					1330:1339	positron emission tomography	1312:1339	positron emission tomography (PET)	1312:1345	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	11	12	theme	neuroinflammation	2145:2161	arg1	model					2136:2140	a well-characterised animal model	2108:2140	a well-characterised animal model of neuroinflammation	2108:2161	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	12	13	theme	critical	2215:2222	arg1	targets					2224:2230	critical targets	2215:2230	critical targets that may modulate neuroinflammation in neurodegenerative diseases	2215:2296	These data represent a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases.
33993882	1	14	theme	BACKGROUND	106:115	arg1	pathology					152:160	an underlying pathology	138:160	an underlying pathology	138:160	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	1	14	theme	BACKGROUND	106:115	arg1	Neuroinflammation					117:133	BACKGROUND Neuroinflammation	106:133	BACKGROUND Neuroinflammation	106:133	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	4	15	from	Changes	666:672	arg1	N-glycosylation					677:691	N-glycosylation	677:691	N-glycosylation	677:691	Changes in N-glycosylation can ultimately affect glycoproteins' functions, which will have an impact on cell machinery.
33993882	5	16	theme	potential	891:899	arg1	target					901:906	a potential target	889:906	a potential target for future therapies	889:927	Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies.
33993882	1	17	theme	underlying	141:150	arg1	pathology					152:160	an underlying pathology	138:160	an underlying pathology	138:160	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	1	17	theme	underlying	141:150	arg1	Neuroinflammation					117:133	BACKGROUND Neuroinflammation	106:133	BACKGROUND Neuroinflammation	106:133	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	7	18	theme	post-mortem	1097:1107	arg1	characterisation					1135:1150	In vivo and post-mortem, quantitative and spatial characterisation	1085:1150	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome	1085:1190	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS.
33993882	2	19	theme	specific	252:259	arg1	glycosylation					328:340	glycosylation	328:340	glycosylation (i.e., post-translational addition of glycans to the protein structure)	328:412	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	2	19	theme	specific	252:259	arg1	pathway					271:277	A specific molecular pathway	250:277	A specific molecular pathway that has been overlooked in neuroinflammation	250:323	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	8	20	theme	quantitative	1348:1359	arg1	histology					1361:1369	quantitative histology	1348:1369	quantitative histology	1348:1369	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	5	21	from	characterisation	797:812	arg1	scenario					868:875	a neuroinflammatory scenario	848:875	a neuroinflammatory scenario	848:875	Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies.
33993882	11	22	theme	first	2049:2053	arg1	time					2055:2058	the first time	2045:2058	the first time	2045:2058	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	9	23	theme	LPS-induced	1589:1599	arg1	neuroinflammation					1601:1617	LPS-induced neuroinflammation	1589:1617	LPS-induced neuroinflammation	1589:1617	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	11	24	theme	N-glycomic	2086:2095	arg1	changes					2097:2103	N-glycomic changes	2086:2103	N-glycomic changes	2086:2103	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	8	25	theme	transcription-quantitative	1380:1405	arg1	RT-qPCR					1434:1440	RT-qPCR	1434:1440	RT-qPCR	1434:1440	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	8	25	theme	transcription-quantitative	1380:1405	arg1	reaction					1424:1431	reverse transcription-quantitative polymerase chain reaction	1372:1431	reverse transcription-quantitative polymerase chain reaction (RT-qPCR)	1372:1441	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	9	26	theme	significant	1622:1632	arg1	decrease					1634:1641	a significant decrease	1620:1641	a significant decrease in the abundance of sialylated and core fucosylated structures	1620:1704	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	8	27	theme	chain	1418:1422	arg1	RT-qPCR					1434:1440	RT-qPCR	1434:1440	RT-qPCR	1434:1440	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	8	27	theme	chain	1418:1422	arg1	reaction					1424:1431	reverse transcription-quantitative polymerase chain reaction	1372:1431	reverse transcription-quantitative polymerase chain reaction (RT-qPCR)	1372:1441	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	0	28	theme	rodent	92:97	arg1	brain					99:103	the rodent brain	88:103	the rodent brain	88:103	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.
33993882	11	29	theme	complete	2064:2071	arg1	profiling					2073:2081	the complete profiling	2060:2081	the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation	2060:2161	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	4	30	gly	glycoproteins	715:727	arg1	glycoproteins					715:727	glycoproteins' functions	715:738	glycoproteins' functions	715:738	Changes in N-glycosylation can ultimately affect glycoproteins' functions, which will have an impact on cell machinery.
33993882	11	31	theme	well-characterised	2110:2127	arg1	model					2136:2140	a well-characterised animal model	2108:2140	a well-characterised animal model of neuroinflammation	2108:2161	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	6	32	theme	rat	1033:1035	arg1	brain					1037:1041	the adult rat brain	1023:1041	the adult rat brain	1023:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	9	33	dep	showing	1581:1587	arg1	whereas					1760:1766	whereas	1760:1766	whereas	1760:1766	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	9	34	theme	sialylated	1663:1672	arg1	abundance					1650:1658	the abundance	1646:1658	the abundance of sialylated and core fucosylated structures	1646:1704	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	4	35	theme	cell	770:773	arg1	machinery					775:783	cell machinery	770:783	cell machinery	770:783	Changes in N-glycosylation can ultimately affect glycoproteins' functions, which will have an impact on cell machinery.
33993882	3	36	theme	glycosylation	453:465	arg1	N-glycosylation					415:429	N-glycosylation	415:429	N-glycosylation	415:429	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	36	theme	glycosylation	453:465	arg1	type					445:448	a specific type	434:448	a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation	434:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	0	37	theme	Complete	0:7	arg1	characterisation					17:32	Complete spatial characterisation	0:32	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.	0:104	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.
33993882	9	38	theme	core	1678:1681	arg1	structures					1695:1704	core fucosylated structures	1678:1704	core fucosylated structures	1678:1704	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	2	39	theme	protein	395:401	arg1	structure					403:411	the protein structure	391:411	the protein structure	391:411	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	9	40	theme	structures	1695:1704	arg1	abundance					1650:1658	the abundance	1646:1658	the abundance of sialylated and core fucosylated structures	1646:1704	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	8	41	theme	laser	1486:1490	arg1	spectrometry					1519:1530	matrix-assisted laser desorption ionisation mass spectrometry	1470:1530	matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI)	1470:1550	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	0	42	theme	N-glycosylation	37:51	arg1	characterisation					17:32	Complete spatial characterisation	0:32	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.	0:104	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.
33993882	5	43	theme	alterations	833:843	arg1	characterisation					797:812	characterisation	797:812	characterisation of N-glycosylation alterations in a neuroinflammatory scenario	797:875	Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies.
33993882	11	44	dep	CONCLUSIONS	2005:2015	arg1	show					2036:2039	show	2036:2039	show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation	2036:2161	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	6	45	theme	neuroinflammation	1066:1082	arg1	injection					982:990	the unilateral intrastriatal injection	953:990	the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain	953:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	45	theme	neuroinflammation	1066:1082	arg1	model					1057:1061	a model	1055:1061	a model of neuroinflammation	1055:1082	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	45	theme	neuroinflammation	1066:1082	arg1	METHODS					930:936	METHODS	930:936	METHODS With that aim	930:950	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	10	46	theme	precise	1939:1945	arg1	comparison					1947:1956	precise comparison	1939:1956	precise comparison between normal and diseased brain hemispheres	1939:2002	This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres.
33993882	8	47	theme	ionisation	1503:1512	arg1	spectrometry					1519:1530	matrix-assisted laser desorption ionisation mass spectrometry	1470:1530	matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI)	1470:1550	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	2	48	theme	glycans	380:386	arg1	addition					368:375	post-translational addition	349:375	post-translational addition of glycans to the protein structure	349:411	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	0	49	theme	striatal	58:65	arg1	neuroinflammation					67:83	striatal neuroinflammation	58:83	striatal neuroinflammation in the rodent brain	58:103	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.
33993882	9	50	gly	fucosylated	1683:1693	arg1	structures					1695:1704	core fucosylated structures	1678:1704	core fucosylated structures	1678:1704	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	10	51	theme	brain	1986:1990	arg1	hemispheres					1992:2002	normal and diseased brain hemispheres	1966:2002	normal and diseased brain hemispheres	1966:2002	This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres.
33993882	8	52	theme	spectrometry	1519:1530	arg1	MALDI-MSI					1541:1549	MALDI-MSI	1541:1549	MALDI-MSI	1541:1549	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	8	52	theme	spectrometry	1519:1530	arg1	imaging					1532:1538	matrix-assisted laser desorption ionisation mass spectrometry imaging	1470:1538	matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI)	1470:1550	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	3	53	theme	nervous	503:509	arg1	CNS					519:521	CNS	519:521	CNS	519:521	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	53	theme	nervous	503:509	arg1	system					511:516	the central nervous system	491:516	the central nervous system (CNS)	491:522	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	1	54	theme	neurological	169:180	arg1	conditions					182:191	all neurological conditions	165:191	all neurological conditions	165:191	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	7	55	theme	1-week	1209:1214	arg1	post-injection					1216:1229	1-week post-injection	1209:1229	1-week post-injection of LPS	1209:1236	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS.
33993882	6	56	from	injection	982:990	arg1	brain					1037:1041	the adult rat brain	1023:1041	the adult rat brain	1023:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	57	theme	unilateral	957:966	arg1	METHODS					930:936	METHODS	930:936	METHODS With that aim	930:950	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	57	theme	unilateral	957:966	arg1	model					1057:1061	a model	1055:1061	a model of neuroinflammation	1055:1082	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	57	theme	unilateral	957:966	arg1	injection					982:990	the unilateral intrastriatal injection	953:990	the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain	953:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	9	58	from	decrease	1634:1641	arg1	abundance					1650:1658	the abundance	1646:1658	the abundance of sialylated and core fucosylated structures	1646:1704	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	3	59	theme	congenital	549:558	arg1	diseases					574:581	congenital glycosylation diseases	549:581	congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation	549:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	7	60	dep	In	1085:1086	arg1	vivo					1088:1091	vivo	1088:1091	vivo	1088:1091	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS.
33993882	11	61	theme	changes	2097:2103	arg1	profiling					2073:2081	the complete profiling	2060:2081	the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation	2060:2161	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	5	62	theme	future	912:917	arg1	therapies					919:927	future therapies	912:927	future therapies	912:927	Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies.
33993882	4	63	contain	have	752:755	arg2	impact					760:765	an impact	757:765	an impact on cell machinery	757:783	Changes in N-glycosylation can ultimately affect glycoproteins' functions, which will have an impact on cell machinery.
33993882	4	63	contain	have	752:755	arg1	functions					730:738	glycoproteins' functions	715:738	glycoproteins' functions	715:738	Changes in N-glycosylation can ultimately affect glycoproteins' functions, which will have an impact on cell machinery.
33993882	6	64	theme	adult	1027:1031	arg1	brain					1037:1041	the adult rat brain	1023:1041	the adult rat brain	1023:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	8	65	theme	positron	1312:1319	arg1	PET					1342:1344	PET	1342:1344	PET	1342:1344	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	8	65	theme	positron	1312:1319	arg1	tomography					1330:1339	positron emission tomography	1312:1339	positron emission tomography (PET)	1312:1345	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	11	66	theme	animal	2129:2134	arg1	model					2136:2140	a well-characterised animal model	2108:2140	a well-characterised animal model of neuroinflammation	2108:2161	CONCLUSIONS Together, our data show for the first time the complete profiling of N-glycomic changes in a well-characterised animal model of neuroinflammation.
33993882	2	67	theme	molecular	261:269	arg1	glycosylation					328:340	glycosylation	328:340	glycosylation (i.e., post-translational addition of glycans to the protein structure)	328:412	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	2	67	theme	molecular	261:269	arg1	pathway					271:277	A specific molecular pathway	250:277	A specific molecular pathway that has been overlooked in neuroinflammation	250:323	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	9	68	dep	seen	1710:1713	arg1	%					1733:1733	approximately 7.5%	1716:1733	approximately 7.5%	1716:1733	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	9	68	dep	seen	1710:1713	arg1	%					1742:1742	8.5%	1739:1742	8.5%	1739:1742	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	9	69	theme	brain	1568:1572	arg1	region					1574:1579	the brain region	1564:1579	the brain region	1564:1579	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	7	70	theme	In	1085:1086	arg1	characterisation					1135:1150	In vivo and post-mortem, quantitative and spatial characterisation	1085:1150	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome	1085:1190	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS.
33993882	3	71	theme	neuropathological	598:614	arg1	symptoms					616:623	neuropathological symptoms	598:623	neuropathological symptoms such as epilepsy and mental retardation	598:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	71	theme	neuropathological	598:614	arg1	epilepsy					633:640	epilepsy	633:640	epilepsy	633:640	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	71	theme	neuropathological	598:614	arg1	retardation					653:663	mental retardation	646:663	mental retardation	646:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	8	72	theme	multifaceted	1281:1292	arg1	approach					1294:1301	a multifaceted approach	1279:1301	a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI)	1279:1550	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	6	73	theme	lipopolysaccharide	995:1012	arg1	METHODS					930:936	METHODS	930:936	METHODS With that aim	930:950	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	73	theme	lipopolysaccharide	995:1012	arg1	model					1057:1061	a model	1055:1061	a model of neuroinflammation	1055:1082	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	6	73	theme	lipopolysaccharide	995:1012	arg1	injection					982:990	the unilateral intrastriatal injection	953:990	the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain	953:1041	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	3	74	theme	mental	646:651	arg1	retardation					653:663	mental retardation	646:663	mental retardation	646:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	1	75	theme	pathology	152:160	arg1	understanding					198:210	the understanding	194:210	the understanding	194:210	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	9	76	dep	increased	1810:1818	arg1	%					1825:1825	13.5%	1821:1825	13.5%	1821:1825	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	10	77	theme	N-glycans	1919:1927	arg1	distribution					1903:1914	a high-resolution spatial distribution	1877:1914	a high-resolution spatial distribution of N-glycans	1877:1927	This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres.
33993882	8	78	theme	reverse	1372:1378	arg1	RT-qPCR					1434:1440	RT-qPCR	1434:1440	RT-qPCR	1434:1440	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	8	78	theme	reverse	1372:1378	arg1	reaction					1424:1431	reverse transcription-quantitative polymerase chain reaction	1372:1431	reverse transcription-quantitative polymerase chain reaction (RT-qPCR)	1372:1441	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	1	79	theme	conditions	182:191	arg1	pathology					152:160	an underlying pathology	138:160	an underlying pathology	138:160	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	1	79	theme	conditions	182:191	arg1	Neuroinflammation					117:133	BACKGROUND Neuroinflammation	106:133	BACKGROUND Neuroinflammation	106:133	BACKGROUND Neuroinflammation is an underlying pathology of all neurological conditions, the understanding of which is still being comprehended.
33993882	7	80	theme	neuroinflammation	1160:1176	arg1	characterisation					1135:1150	In vivo and post-mortem, quantitative and spatial characterisation	1085:1150	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome	1085:1190	In vivo and post-mortem, quantitative and spatial characterisation of both neuroinflammation and N-glycome was performed at 1-week post-injection of LPS.
33993882	8	81	theme	polymerase	1407:1416	arg1	RT-qPCR					1434:1440	RT-qPCR	1434:1440	RT-qPCR	1434:1440	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	8	81	theme	polymerase	1407:1416	arg1	reaction					1424:1431	reverse transcription-quantitative polymerase chain reaction	1372:1431	reverse transcription-quantitative polymerase chain reaction (RT-qPCR)	1372:1441	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	12	82	theme	neurodegenerative	2271:2287	arg1	diseases					2289:2296	neurodegenerative diseases	2271:2296	neurodegenerative diseases	2271:2296	These data represent a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases.
33993882	12	83	from	neuroinflammation	2250:2266	arg1	diseases					2289:2296	neurodegenerative diseases	2271:2296	neurodegenerative diseases	2271:2296	These data represent a pioneering step to identify critical targets that may modulate neuroinflammation in neurodegenerative diseases.
33993882	0	84	from	neuroinflammation	67:83	arg1	brain					99:103	the rodent brain	88:103	the rodent brain	88:103	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.
33993882	3	85	theme	cardinal	474:481	arg1	role					483:486	a cardinal role	472:486	a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation	472:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	5	86	theme	neuroinflammatory	850:866	arg1	scenario					868:875	a neuroinflammatory scenario	848:875	a neuroinflammatory scenario	848:875	Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies.
33993882	6	87	with	METHODS	930:936	arg1	aim					948:950	that aim	943:950	that aim	943:950	METHODS With that aim, the unilateral intrastriatal injection of lipopolysaccharide (LPS) in the adult rat brain was used as a model of neuroinflammation.
33993882	9	88	theme	fucosylated	1683:1693	arg1	structures					1695:1704	core fucosylated structures	1678:1704	core fucosylated structures	1678:1704	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	8	89	theme	liquid	1444:1449	arg1	chromatography					1451:1464	liquid chromatography	1444:1464	liquid chromatography	1444:1464	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	10	90	theme	normal	1966:1971	arg1	hemispheres					1992:2002	normal and diseased brain hemispheres	1966:2002	normal and diseased brain hemispheres	1966:2002	This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres.
33993882	3	91	theme	central	495:501	arg1	CNS					519:521	CNS	519:521	CNS	519:521	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	91	theme	central	495:501	arg1	system					511:516	the central nervous system	491:516	the central nervous system (CNS)	491:522	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	5	92	theme	N-glycosylation	817:831	arg1	alterations					833:843	N-glycosylation alterations	817:843	N-glycosylation alterations	817:843	Therefore, characterisation of N-glycosylation alterations in a neuroinflammatory scenario can provide a potential target for future therapies.
33993882	8	93	theme	matrix-assisted	1470:1484	arg1	spectrometry					1519:1530	matrix-assisted laser desorption ionisation mass spectrometry	1470:1530	matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI)	1470:1550	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	3	94	from	role	483:486	arg1	CNS					519:521	CNS	519:521	CNS	519:521	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	94	from	role	483:486	arg1	system					511:516	the central nervous system	491:516	the central nervous system (CNS)	491:522	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	95	theme	specific	436:443	arg1	N-glycosylation					415:429	N-glycosylation	415:429	N-glycosylation	415:429	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	3	95	theme	specific	436:443	arg1	type					445:448	a specific type	434:448	a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation	434:663	N-glycosylation is a specific type of glycosylation with a cardinal role in the central nervous system (CNS), which is highlighted by congenital glycosylation diseases that result in neuropathological symptoms such as epilepsy and mental retardation.
33993882	8	96	theme	desorption	1492:1501	arg1	spectrometry					1519:1530	matrix-assisted laser desorption ionisation mass spectrometry	1470:1530	matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI)	1470:1550	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	4	97	from	impact	760:765	arg1	machinery					775:783	cell machinery	770:783	cell machinery	770:783	Changes in N-glycosylation can ultimately affect glycoproteins' functions, which will have an impact on cell machinery.
33993882	10	98	theme	spatial	1895:1901	arg1	distribution					1903:1914	a high-resolution spatial distribution	1877:1914	a high-resolution spatial distribution of N-glycans	1877:1927	This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres.
33993882	10	99	theme	diseased	1977:1984	arg1	hemispheres					1992:2002	normal and diseased brain hemispheres	1966:2002	normal and diseased brain hemispheres	1966:2002	This was confirmed by MALDI-MSI, which provided a high-resolution spatial distribution of N-glycans, allowing precise comparison between normal and diseased brain hemispheres.
33993882	8	100	theme	mass	1514:1517	arg1	spectrometry					1519:1530	matrix-assisted laser desorption ionisation mass spectrometry	1470:1530	matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI)	1470:1550	These aspects were investigated through a multifaceted approach based on positron emission tomography (PET), quantitative histology, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), liquid chromatography and matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI).
33993882	2	101	theme	post-translational	349:366	arg1	addition					368:375	post-translational addition	349:375	post-translational addition of glycans to the protein structure	349:411	A specific molecular pathway that has been overlooked in neuroinflammation is glycosylation (i.e., post-translational addition of glycans to the protein structure).
33993882	9	102	from	RESULTS	1553:1559	arg1	region					1574:1579	the brain region	1564:1579	the brain region	1564:1579	RESULTS In the brain region showing LPS-induced neuroinflammation, a significant decrease in the abundance of sialylated and core fucosylated structures was seen (approximately 7.5% and 8.5%, respectively), whereas oligomannose N-glycans were significantly increased (13.5%).
33993882	0	103	theme	spatial	9:15	arg1	characterisation					17:32	Complete spatial characterisation	0:32	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.	0:104	Complete spatial characterisation of N-glycosylation upon striatal neuroinflammation in the rodent brain.
32258897	9	0	theme	total	1379:1383	arg1	N-glycans					1385:1393	total N-glycans	1379:1393	total N-glycans	1379:1393	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	9	1	theme	N-glycans	1385:1393	arg1	N-glycans					1385:1393	total N-glycans	1379:1393	total N-glycans	1379:1393	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	9	1	theme	N-glycans	1385:1393	arg1	%					1374:1374	∼42%	1371:1374	∼42% of total N-glycans	1371:1393	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	3	2	from	differences	481:491	arg1	size					496:499	size	496:499	size	496:499	N-glycan site occupancy manifested as distinct differences in size and isoelectric point.
32258897	3	2	from	differences	481:491	arg1	point					517:521	isoelectric point	505:521	isoelectric point	505:521	N-glycan site occupancy manifested as distinct differences in size and isoelectric point.
32258897	4	3	theme	glycan	775:780	arg1	profiles					782:789	overall glycan profiles	767:789	overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	767:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	4	theme	moieties	561:568	arg1	analysis					528:535	The analysis	524:535	The analysis of complex carbohydrate moieties of R27T	524:576	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	7	5	theme	bi-	1083:1085	arg1	mixture					1072:1078	a mixture	1070:1078	a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions	1070:1162	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	4	6	theme	overall	767:773	arg1	profiles					782:789	overall glycan profiles	767:789	overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	767:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	9	7	gly	di-sialylated	1402:1414	arg1	structure					1447:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	4	8	theme	quality	639:645	arg1	composition					695:705	antennary composition	685:705	antennary composition	685:705	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	8	theme	quality	639:645	arg1	sialylation					708:718	sialylation	708:718	sialylation	708:718	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	8	theme	quality	639:645	arg1	fucosylation					671:682	core fucosylation	666:682	core fucosylation	666:682	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	8	theme	quality	639:645	arg1	extensions					741:750	N-acetyllactosamine extensions	721:750	N-acetyllactosamine extensions	721:750	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	8	theme	quality	639:645	arg1	attributes					647:656	the common biopharmaceutical glycosylation critical quality attributes	587:656	the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	587:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	8	theme	quality	639:645	arg1	profiles					782:789	overall glycan profiles	767:789	overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	767:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	8	theme	quality	639:645	arg1	linkages					753:760	linkages	753:760	linkages	753:760	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	9	theme	carbohydrate	548:559	arg1	moieties					561:568	complex carbohydrate moieties	540:568	complex carbohydrate moieties of R27T	540:576	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	10	theme	interaction	833:843	arg1	chromatography					869:882	weak anion-exchange and hydrophilic interaction high-performance liquid chromatography	797:882	chromatography	869:882	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	11	theme	hydrophilic	821:831	arg1	chromatography					869:882	weak anion-exchange and hydrophilic interaction high-performance liquid chromatography	797:882	chromatography	869:882	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	1	12	contain	possesses	158:166	arg1	version					127:133	a biobetter version	115:133	a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a	115:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	1	12	contain	possesses	158:166	arg2	site					196:199	an additional glycosylation site	168:199	an additional glycosylation site compared with rhIFN-β 1a	168:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	1	13	gly	glycosylation	182:194	arg2	site					196:199	an additional glycosylation site	168:199	an additional glycosylation site compared with rhIFN-β 1a	168:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	4	14	theme	liquid	862:867	arg1	chromatography					869:882	weak anion-exchange and hydrophilic interaction high-performance liquid chromatography	797:882	chromatography	869:882	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	8	15	from	Rebif	1329:1333	arg1	abundant					1304:1311	abundant	1304:1311	abundant	1304:1311	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	4	16	theme	2-aminobenzoic	889:902	arg1	N-glycans					917:925	2-aminobenzoic acid-labeled N-glycans	889:925	2-aminobenzoic acid-labeled N-glycans	889:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	3	17	theme	distinct	472:479	arg1	differences					481:491	distinct differences	472:491	distinct differences in size and isoelectric point	472:521	N-glycan site occupancy manifested as distinct differences in size and isoelectric point.
32258897	3	18	theme	N-glycan	434:441	arg1	occupancy					448:456	N-glycan site occupancy	434:456	N-glycan site occupancy	434:456	N-glycan site occupancy manifested as distinct differences in size and isoelectric point.
32258897	9	19	theme	di-sialylated	1402:1414	arg1	structure					1447:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	3	20	theme	site	443:446	arg1	occupancy					448:456	N-glycan site occupancy	434:456	N-glycan site occupancy	434:456	N-glycan site occupancy manifested as distinct differences in size and isoelectric point.
32258897	2	21	theme	R27T	285:288	arg1	heterogeneity					268:280	N-glycosylation heterogeneity	252:280	N-glycosylation heterogeneity	252:280	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	1	22	theme	additional	171:180	arg1	site					196:199	an additional glycosylation site	168:199	an additional glycosylation site compared with rhIFN-β 1a	168:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	2	23	gly	heterogeneity	268:280	arg1	R27T					285:288	R27T	285:288	R27T	285:288	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	6	24	theme	single-glycosylated	999:1017	arg1	form					1019:1022	the single-glycosylated form	995:1022	the single-glycosylated form	995:1022	94% R27T, while the single-glycosylated form accounted for 6% R27T.
32258897	2	25	theme	occupancy	325:333	arg1	macro-heterogeneity					350:368	macro-heterogeneity	350:368	macro-heterogeneity	350:368	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	25	theme	occupancy	325:333	arg1	heterogeneity					335:347	N-glycan site occupancy heterogeneity	311:347	N-glycan site occupancy heterogeneity (macro-heterogeneity)	311:369	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	1	26	theme	glycosylation	182:194	arg1	site					196:199	an additional glycosylation site	168:199	an additional glycosylation site compared with rhIFN-β 1a	168:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	0	27	theme	Glycosylation	0:12	arg1	Heterogeneity					14:26	Glycosylation Heterogeneity	0:26	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).	0:89	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	4	28	theme	biopharmaceutical	598:614	arg1	composition					695:705	antennary composition	685:705	antennary composition	685:705	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	28	theme	biopharmaceutical	598:614	arg1	sialylation					708:718	sialylation	708:718	sialylation	708:718	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	28	theme	biopharmaceutical	598:614	arg1	fucosylation					671:682	core fucosylation	666:682	core fucosylation	666:682	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	28	theme	biopharmaceutical	598:614	arg1	extensions					741:750	N-acetyllactosamine extensions	721:750	N-acetyllactosamine extensions	721:750	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	28	theme	biopharmaceutical	598:614	arg1	attributes					647:656	the common biopharmaceutical glycosylation critical quality attributes	587:656	the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	587:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	28	theme	biopharmaceutical	598:614	arg1	profiles					782:789	overall glycan profiles	767:789	overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	767:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	28	theme	biopharmaceutical	598:614	arg1	linkages					753:760	linkages	753:760	linkages	753:760	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	2	29	theme	site	320:323	arg1	macro-heterogeneity					350:368	macro-heterogeneity	350:368	macro-heterogeneity	350:368	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	29	theme	site	320:323	arg1	heterogeneity					335:347	N-glycan site occupancy heterogeneity	311:347	N-glycan site occupancy heterogeneity (macro-heterogeneity)	311:369	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	30	theme	moieties	402:409	arg1	macro-heterogeneity					350:368	macro-heterogeneity	350:368	macro-heterogeneity	350:368	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	30	theme	moieties	402:409	arg1	complexity					375:384	complexity	375:384	complexity of carbohydrate moieties (micro-heterogeneity)	375:431	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	30	theme	moieties	402:409	arg1	heterogeneity					335:347	N-glycan site occupancy heterogeneity	311:347	N-glycan site occupancy heterogeneity (macro-heterogeneity)	311:369	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	0	31	theme	Hyperglycosylated	31:47	arg1	rhIFN-β					81:87	rhIFN-β	81:87	rhIFN-β	81:87	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	0	31	theme	Hyperglycosylated	31:47	arg1	Interferon-β					67:78	Hyperglycosylated Recombinant Human Interferon-β	31:78	Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β)	31:88	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	4	32	theme	common	591:596	arg1	composition					695:705	antennary composition	685:705	antennary composition	685:705	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	32	theme	common	591:596	arg1	sialylation					708:718	sialylation	708:718	sialylation	708:718	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	32	theme	common	591:596	arg1	fucosylation					671:682	core fucosylation	666:682	core fucosylation	666:682	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	32	theme	common	591:596	arg1	extensions					741:750	N-acetyllactosamine extensions	721:750	N-acetyllactosamine extensions	721:750	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	32	theme	common	591:596	arg1	attributes					647:656	the common biopharmaceutical glycosylation critical quality attributes	587:656	the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	587:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	32	theme	common	591:596	arg1	profiles					782:789	overall glycan profiles	767:789	overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	767:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	32	theme	common	591:596	arg1	linkages					753:760	linkages	753:760	linkages	753:760	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	7	33	theme	arm	1183:1185	arg1	fucose					1187:1192	outer arm fucose	1177:1192	outer arm fucose	1177:1192	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	2	34	theme	N-glycan	311:318	arg1	macro-heterogeneity					350:368	macro-heterogeneity	350:368	macro-heterogeneity	350:368	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	34	theme	N-glycan	311:318	arg1	heterogeneity					335:347	N-glycan site occupancy heterogeneity	311:347	N-glycan site occupancy heterogeneity (macro-heterogeneity)	311:369	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	6	35	theme	6	1038:1038	arg1	%					1039:1039	%	1039:1039	%	1039:1039	94% R27T, while the single-glycosylated form accounted for 6% R27T.
32258897	2	36	gly	N-glycosylation	252:266	arg1	R27T					285:288	R27T	285:288	R27T	285:288	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	4	37	theme	critical	630:637	arg1	composition					695:705	antennary composition	685:705	antennary composition	685:705	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	37	theme	critical	630:637	arg1	sialylation					708:718	sialylation	708:718	sialylation	708:718	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	37	theme	critical	630:637	arg1	fucosylation					671:682	core fucosylation	666:682	core fucosylation	666:682	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	37	theme	critical	630:637	arg1	extensions					741:750	N-acetyllactosamine extensions	721:750	N-acetyllactosamine extensions	721:750	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	37	theme	critical	630:637	arg1	attributes					647:656	the common biopharmaceutical glycosylation critical quality attributes	587:656	the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	587:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	37	theme	critical	630:637	arg1	profiles					782:789	overall glycan profiles	767:789	overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	767:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	37	theme	critical	630:637	arg1	linkages					753:760	linkages	753:760	linkages	753:760	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	1	38	theme	biobetter	117:125	arg1	version					127:133	a biobetter version	115:133	a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a	115:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	3	39	theme	isoelectric	505:515	arg1	point					517:521	isoelectric point	505:521	isoelectric point	505:521	N-glycan site occupancy manifested as distinct differences in size and isoelectric point.
32258897	0	40	theme	Human	61:65	arg1	rhIFN-β					81:87	rhIFN-β	81:87	rhIFN-β	81:87	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	0	40	theme	Human	61:65	arg1	Interferon-β					67:78	Hyperglycosylated Recombinant Human Interferon-β	31:78	Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β)	31:88	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	4	41	theme	glycosylation	616:628	arg1	composition					695:705	antennary composition	685:705	antennary composition	685:705	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	41	theme	glycosylation	616:628	arg1	sialylation					708:718	sialylation	708:718	sialylation	708:718	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	41	theme	glycosylation	616:628	arg1	fucosylation					671:682	core fucosylation	666:682	core fucosylation	666:682	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	41	theme	glycosylation	616:628	arg1	extensions					741:750	N-acetyllactosamine extensions	721:750	N-acetyllactosamine extensions	721:750	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	41	theme	glycosylation	616:628	arg1	attributes					647:656	the common biopharmaceutical glycosylation critical quality attributes	587:656	the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	587:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	41	theme	glycosylation	616:628	arg1	profiles					782:789	overall glycan profiles	767:789	overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans	767:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	41	theme	glycosylation	616:628	arg1	linkages					753:760	linkages	753:760	linkages	753:760	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	9	42	theme	major	1340:1344	arg1	N-glycan					1346:1353	The major N-glycan	1336:1353	The major N-glycan	1336:1353	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	9	43	contain	had	1396:1398	arg1	N-glycan					1346:1353	The major N-glycan	1336:1353	The major N-glycan	1336:1353	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	9	43	contain	had	1396:1398	arg2	structure					1447:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	1	44	theme	rhIFN-β	215:221	arg1	1a					223:224	rhIFN-β 1a	215:224	rhIFN-β 1a	215:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	0	45	theme	Recombinant	49:59	arg1	rhIFN-β					81:87	rhIFN-β	81:87	rhIFN-β	81:87	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	0	45	theme	Recombinant	49:59	arg1	Interferon-β					67:78	Hyperglycosylated Recombinant Human Interferon-β	31:78	Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β)	31:88	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	4	46	theme	R27T	573:576	arg1	moieties					561:568	complex carbohydrate moieties	540:568	complex carbohydrate moieties of R27T	540:576	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	7	47	theme	outer	1177:1181	arg1	fucose					1187:1192	outer arm fucose	1177:1192	outer arm fucose	1177:1192	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	0	48	gly	Heterogeneity	14:26	arg1	rhIFN-β					81:87	rhIFN-β	81:87	rhIFN-β	81:87	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	0	48	gly	Heterogeneity	14:26	arg1	Interferon-β					67:78	Hyperglycosylated Recombinant Human Interferon-β	31:78	Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β)	31:88	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	9	49	dep	di-sialylated	1402:1414	arg1	core-fucosylated					1417:1432	core-fucosylated	1417:1432	core-fucosylated	1417:1432	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	6	50	dep	R27T	983:986	arg1	accounted					1024:1032	accounted	1024:1032	accounted for 6% R27T	1024:1044	94% R27T, while the single-glycosylated form accounted for 6% R27T.
32258897	6	50	dep	R27T	983:986	arg1	%					981:981	94%	979:981	94%	979:981	94% R27T, while the single-glycosylated form accounted for 6% R27T.
32258897	8	51	theme	Sialic	1224:1229	arg1	N-acetyl-					1252:1260	N-acetyl-	1252:1260	N-acetyl-	1252:1260	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	51	theme	Sialic	1224:1229	arg1	acid					1288:1291	N-glycolyl-neuraminic acid	1266:1291	N-glycolyl-neuraminic acid	1266:1291	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	51	theme	Sialic	1224:1229	arg1	variants					1242:1249	Sialic acid major variants	1224:1249	Sialic acid major variants	1224:1249	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	9	52	theme	bi-antennary	1434:1445	arg1	structure					1447:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	a di-sialylated, core-fucosylated bi-antennary structure	1400:1455	The major N-glycan, accounting for ∼42% of total N-glycans, had a di-sialylated, core-fucosylated bi-antennary structure.
32258897	7	53	theme	N-acetyllactosamine	1133:1151	arg1	extensions					1153:1162	N-acetyllactosamine extensions	1133:1162	N-acetyllactosamine extensions	1133:1162	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	0	54	theme	Interferon-β	67:78	arg1	Heterogeneity					14:26	Glycosylation Heterogeneity	0:26	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).	0:89	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	8	55	from	R27T	1316:1319	arg1	abundant					1304:1311	abundant	1304:1311	abundant	1304:1311	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	6	56	theme	%	1039:1039	arg1	R27T					1041:1044	6% R27T	1038:1044	6% R27T	1038:1044	94% R27T, while the single-glycosylated form accounted for 6% R27T.
32258897	0	57	gly	Hyperglycosylated	31:47	arg1	rhIFN-β					81:87	rhIFN-β	81:87	rhIFN-β	81:87	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	0	57	gly	Hyperglycosylated	31:47	arg1	Interferon-β					67:78	Hyperglycosylated Recombinant Human Interferon-β	31:78	Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β)	31:88	Glycosylation Heterogeneity of Hyperglycosylated Recombinant Human Interferon-β (rhIFN-β).
32258897	7	58	theme	glycans	1114:1120	arg1	mixture					1072:1078	a mixture	1070:1078	a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions	1070:1162	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	8	59	from	abundant	1304:1311	arg1	R27T					1316:1319	R27T	1316:1319	R27T	1316:1319	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	59	from	abundant	1304:1311	arg1	Rebif					1329:1333	Rebif	1329:1333	Rebif	1329:1333	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	2	60	gly	heterogeneity	335:347	arg1	micro-heterogeneity					412:430	micro-heterogeneity	412:430	micro-heterogeneity	412:430	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	60	gly	heterogeneity	335:347	arg1	moieties					402:409	carbohydrate moieties	389:409	carbohydrate moieties (micro-heterogeneity)	389:431	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	5	61	gly	double-glycosylated	932:950	arg1	form					952:955	The double-glycosylated form	928:955	The double-glycosylated form	928:955	The double-glycosylated form accounted for approx.
32258897	1	62	theme	rhIFN-β	138:144	arg1	version					127:133	a biobetter version	115:133	a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a	115:224	We previously developed a biobetter version of rhIFN-β (R27T) that possesses an additional glycosylation site compared with rhIFN-β 1a.
32258897	4	63	theme	high-performance	845:860	arg1	chromatography					869:882	weak anion-exchange and hydrophilic interaction high-performance liquid chromatography	797:882	chromatography	869:882	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	8	64	theme	acid	1231:1234	arg1	N-acetyl-					1252:1260	N-acetyl-	1252:1260	N-acetyl-	1252:1260	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	64	theme	acid	1231:1234	arg1	acid					1288:1291	N-glycolyl-neuraminic acid	1266:1291	N-glycolyl-neuraminic acid	1266:1291	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	64	theme	acid	1231:1234	arg1	variants					1242:1249	Sialic acid major variants	1224:1249	Sialic acid major variants	1224:1249	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	4	65	theme	acid-labeled	904:915	arg1	N-glycans					917:925	2-aminobenzoic acid-labeled N-glycans	889:925	2-aminobenzoic acid-labeled N-glycans	889:925	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	8	66	theme	major	1236:1240	arg1	N-acetyl-					1252:1260	N-acetyl-	1252:1260	N-acetyl-	1252:1260	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	66	theme	major	1236:1240	arg1	acid					1288:1291	N-glycolyl-neuraminic acid	1266:1291	N-glycolyl-neuraminic acid	1266:1291	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	66	theme	major	1236:1240	arg1	variants					1242:1249	Sialic acid major variants	1224:1249	Sialic acid major variants	1224:1249	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	6	67	gly	single-glycosylated	999:1017	arg1	form					1019:1022	the single-glycosylated form	995:1022	the single-glycosylated form	995:1022	94% R27T, while the single-glycosylated form accounted for 6% R27T.
32258897	4	68	theme	core	666:669	arg1	fucosylation					671:682	core fucosylation	666:682	core fucosylation	666:682	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	2	69	theme	N-glycosylation	252:266	arg1	heterogeneity					268:280	N-glycosylation heterogeneity	252:280	N-glycosylation heterogeneity	252:280	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	7	70	theme	tetra-antennary	1098:1112	arg1	some					1123:1126	some	1123:1126	some	1123:1126	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	7	70	theme	tetra-antennary	1098:1112	arg1	glycans					1114:1120	tetra-antennary glycans	1098:1120	tetra-antennary glycans	1098:1120	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	2	71	theme	carbohydrate	389:400	arg1	micro-heterogeneity					412:430	micro-heterogeneity	412:430	micro-heterogeneity	412:430	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	2	71	theme	carbohydrate	389:400	arg1	moieties					402:409	carbohydrate moieties	389:409	carbohydrate moieties (micro-heterogeneity)	389:431	Herein, we characterized N-glycosylation heterogeneity of R27T, which includes both N-glycan site occupancy heterogeneity (macro-heterogeneity) and complexity of carbohydrate moieties (micro-heterogeneity).
32258897	4	72	theme	N-acetyllactosamine	721:739	arg1	extensions					741:750	N-acetyllactosamine extensions	721:750	N-acetyllactosamine extensions	721:750	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	73	theme	antennary	685:693	arg1	composition					695:705	antennary composition	685:705	antennary composition	685:705	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	4	74	theme	complex	540:546	arg1	moieties					561:568	complex carbohydrate moieties	540:568	complex carbohydrate moieties of R27T	540:576	The analysis of complex carbohydrate moieties of R27T involved the common biopharmaceutical glycosylation critical quality attributes such as core fucosylation, antennary composition, sialylation, N-acetyllactosamine extensions, linkages, and overall glycan profiles using weak anion-exchange and hydrophilic interaction high-performance liquid chromatography with 2-aminobenzoic acid-labeled N-glycans.
32258897	7	75	theme	tri-	1088:1091	arg1	mixture					1072:1078	a mixture	1070:1078	a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions	1070:1162	N-glycans consisted of a mixture of bi-, tri-, and tetra-antennary glycans, some with N-acetyllactosamine extensions, but neither outer arm fucose nor α-galactose was detected.
32258897	5	76	theme	double-glycosylated	932:950	arg1	form					952:955	The double-glycosylated form	928:955	The double-glycosylated form	928:955	The double-glycosylated form accounted for approx.
32258897	8	77	theme	N-glycolyl-neuraminic	1266:1286	arg1	acid					1288:1291	N-glycolyl-neuraminic acid	1266:1291	N-glycolyl-neuraminic acid	1266:1291	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
32258897	8	77	theme	N-glycolyl-neuraminic	1266:1286	arg1	variants					1242:1249	Sialic acid major variants	1224:1249	Sialic acid major variants	1224:1249	Sialic acid major variants, N-acetyl- and N-glycolyl-neuraminic acid, were more abundant in R27T than in Rebif.
34192331	5	0	theme	complex-type	806:817	arg1	N-glycans					819:827	tri-antennary complex-type N-glycans	792:827	tri-antennary complex-type N-glycans	792:827	However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached.
34192331	1	1	contain	has	139:141	arg1	IgG					134:136	IgG	134:136	IgG	134:136	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	1	1	contain	has	139:141	arg2	site					171:174	a conserved N-glycosylation site	143:174	a conserved N-glycosylation site at Asn297	143:184	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	1	1	contain	has	139:141	arg1	G					131:131	Immunoglobulin G	116:131	Immunoglobulin G (IgG)	116:137	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	7	2	theme	N-glycan	1176:1183	arg1	technique					1196:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	8	3	theme	bisecting	1336:1344	arg1	N-acetylglucosamine					1346:1364	a bisecting N-acetylglucosamine	1334:1364	a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure	1334:1414	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	8	3	theme	bisecting	1336:1344	arg1	N-glycan					1312:1319	the largest N-glycan	1300:1319	the largest N-glycan attached	1300:1328	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	7	4	theme	Fc	1082:1083	arg1	region					1085:1090	the Fc region	1078:1090	the Fc region	1078:1090	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	7	5	with	IgGs	1041:1044	arg1	N-glycans					1065:1073	multibranched N-glycans	1051:1073	multibranched N-glycans on the Fc region	1051:1090	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	0	6	theme	complex-type	92:103	arg1	N-glycans					105:113	multibranched complex-type N-glycans	78:113	multibranched complex-type N-glycans	78:113	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	7	7	theme	remodeling	1185:1194	arg1	technique					1196:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	9	8	with	IgGs	1480:1483	arg1	N-glycans					1515:1523	tri- and tetra-antennary N-glycans	1490:1523	tri- and tetra-antennary N-glycans on their Fc region	1490:1542	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	2	9	theme	functions	342:350	arg1	mediator					306:313	a critical mediator	295:313	a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity	295:400	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	2	9	theme	functions	342:350	arg1	N-glycosylation					263:277	N-glycosylation	263:277	N-glycosylation of this site	263:290	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	8	10	theme	largest	1304:1310	arg1	N-acetylglucosamine					1346:1364	a bisecting N-acetylglucosamine	1334:1364	a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure	1334:1414	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	8	10	theme	largest	1304:1310	arg1	N-glycan					1312:1319	the largest N-glycan	1300:1319	the largest N-glycan attached	1300:1328	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	4	11	from	glycoforms	615:624	arg1	region					657:662	the IgG-Fc region	646:662	the IgG-Fc region	646:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	7	12	theme	glycosynthase/oxazoline	1136:1158	arg1	technique					1196:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	9	13	theme	Fc	1534:1535	arg1	region					1537:1542	their Fc region	1528:1542	their Fc region	1528:1542	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	7	14	theme	substrate-based	1160:1174	arg1	technique					1196:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1132:1204	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	7	15	theme	successive	1210:1219	arg1	reactions					1221:1229	successive reactions	1210:1229	successive reactions with glycosyltransferases	1210:1255	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	2	16	theme	site	287:290	arg1	mediator					306:313	a critical mediator	295:313	a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity	295:400	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	2	16	theme	site	287:290	arg1	N-glycosylation					263:277	N-glycosylation	263:277	N-glycosylation of this site	263:290	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	3	17	theme	antibodies	593:602	arg1	efficacy					581:588	the efficacy	577:588	the efficacy of antibodies	577:602	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	8	18	contain	containing	1366:1375	arg2	structure					1406:1414	a sialylated penta-antennary structure	1377:1414	a sialylated penta-antennary structure	1377:1414	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	8	18	contain	containing	1366:1375	arg1	N-acetylglucosamine					1346:1364	a bisecting N-acetylglucosamine	1334:1364	a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure	1334:1414	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	8	18	contain	containing	1366:1375	arg1	N-glycan					1312:1319	the largest N-glycan	1300:1319	the largest N-glycan attached	1300:1328	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	8	19	theme	sialylated	1379:1388	arg1	structure					1406:1414	a sialylated penta-antennary structure	1377:1414	a sialylated penta-antennary structure	1377:1414	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	3	20	theme	functional	544:553	arg1	N-glycans					555:563	functional N-glycans	544:563	functional N-glycans	544:563	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	9	21	theme	similar	1562:1568	arg1	properties					1551:1560	properties	1551:1560	properties similar to IgGs with ordinary bi-antennary N-glycans	1551:1613	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	4	22	theme	complex-type	681:692	arg1	glycoforms					615:624	The major glycoforms	605:624	The major glycoforms of the N-glycans on the IgG-Fc region	605:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	4	22	theme	complex-type	681:692	arg1	N-glycans					694:702	bi-antennary complex-type N-glycans	668:702	bi-antennary complex-type N-glycans	668:702	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	4	23	theme	major	609:613	arg1	glycoforms					615:624	The major glycoforms	605:624	The major glycoforms of the N-glycans on the IgG-Fc region	605:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	4	23	theme	major	609:613	arg1	N-glycans					694:702	bi-antennary complex-type N-glycans	668:702	bi-antennary complex-type N-glycans	668:702	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	3	24	theme	N-glycan	413:420	arg1	heterogenous					477:488	heterogenous	477:488	heterogenous	477:488	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	3	24	theme	N-glycan	413:420	arg1	structures					422:431	the N-glycan structures	409:431	the N-glycan structures attached to the IgG-Fc region	409:461	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	7	25	theme	technique	1196:1204	arg1	reactions					1221:1229	successive reactions	1210:1229	successive reactions with glycosyltransferases	1210:1255	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	7	25	theme	technique	1196:1204	arg1	combination					1117:1127	a combination	1115:1127	a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique	1115:1204	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	5	26	theme	N-glycan	859:866	arg1	technique					879:887	the N-glycan remodeling technique	855:887	the N-glycan remodeling technique	855:887	However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached.
34192331	3	27	theme	IgG-Fc	449:454	arg1	region					456:461	the IgG-Fc region	445:461	the IgG-Fc region	445:461	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	9	28	theme	Fc-mediated	1432:1442	arg1	functions					1453:1461	the Fc-mediated effector functions	1428:1461	the Fc-mediated effector functions	1428:1461	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	2	29	theme	cellular	380:387	arg1	cytotoxicity					389:400	antibody-dependent cellular cytotoxicity	361:400	antibody-dependent cellular cytotoxicity	361:400	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	2	30	gly	N-glycosylation	263:277	arg1	site					287:290	this site	282:290	this site	282:290	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	9	31	theme	effector	1444:1451	arg1	functions					1453:1461	the Fc-mediated effector functions	1428:1461	the Fc-mediated effector functions	1428:1461	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	1	32	theme	Immunoglobulin	116:129	arg1	IgG					134:136	IgG	134:136	IgG	134:136	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	1	32	theme	Immunoglobulin	116:129	arg1	G					131:131	Immunoglobulin G	116:131	Immunoglobulin G (IgG)	116:137	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	1	33	theme	fragment	193:200	arg1	region					222:227	the fragment crystallizable (Fc) region	189:227	the fragment crystallizable (Fc) region	189:227	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	5	34	theme	remodeling	868:877	arg1	technique					879:887	the N-glycan remodeling technique	855:887	the N-glycan remodeling technique	855:887	However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached.
34192331	6	35	theme	IgGs	1020:1023	arg1	properties					1000:1009	the properties	996:1009	the properties of these IgGs	996:1023	At present, little is known about the properties of these IgGs.
34192331	3	36	attach	attached	433:440	arg2	structures					422:431	the N-glycan structures	409:431	the N-glycan structures attached to the IgG-Fc region	409:461	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	3	36	attach	attached	433:440	arg2	heterogenous					477:488	heterogenous	477:488	heterogenous	477:488	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	3	36	attach	attached	433:440	arg1	region					456:461	the IgG-Fc region	445:461	the IgG-Fc region	445:461	While the N-glycan structures attached to the IgG-Fc region are generally heterogenous, IgGs engineered to be homogenously glycosylated with functional N-glycans may improve the efficacy of antibodies.
34192331	2	37	theme	critical	297:304	arg1	mediator					306:313	a critical mediator	295:313	a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity	295:400	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	2	37	theme	critical	297:304	arg1	N-glycosylation					263:277	N-glycosylation	263:277	N-glycosylation of this site	263:290	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	4	38	from	region	657:662	arg1	glycoforms					615:624	The major glycoforms	605:624	The major glycoforms of the N-glycans on the IgG-Fc region	605:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	4	38	from	region	657:662	arg1	N-glycans					694:702	bi-antennary complex-type N-glycans	668:702	bi-antennary complex-type N-glycans	668:702	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	1	39	theme	crystallizable	202:215	arg1	region					222:227	the fragment crystallizable (Fc) region	189:227	the fragment crystallizable (Fc) region	189:227	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	0	40	theme	biological	16:25	arg1	activities					27:36	biological activities	16:36	biological activities	16:36	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	4	41	theme	complex-type	725:736	arg1	N-glycans					738:746	multibranched complex-type N-glycans	711:746	multibranched complex-type N-glycans	711:746	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	4	42	theme	multibranched	711:723	arg1	N-glycans					738:746	multibranched complex-type N-glycans	711:746	multibranched complex-type N-glycans	711:746	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	0	43	theme	anti-HER2	41:49	arg1	antibodies					62:71	anti-HER2 monoclonal antibodies	41:71	anti-HER2 monoclonal antibodies	41:71	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	9	44	with	IgGs	1573:1576	arg1	N-glycans					1605:1613	ordinary bi-antennary N-glycans	1583:1613	ordinary bi-antennary N-glycans	1583:1613	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	9	45	theme	ordinary	1583:1590	arg1	N-glycans					1605:1613	ordinary bi-antennary N-glycans	1583:1613	ordinary bi-antennary N-glycans	1583:1613	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	2	46	theme	antibody-dependent	361:378	arg1	cytotoxicity					389:400	antibody-dependent cellular cytotoxicity	361:400	antibody-dependent cellular cytotoxicity	361:400	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	1	47	theme	Fc	218:219	arg1	region					222:227	the fragment crystallizable (Fc) region	189:227	the fragment crystallizable (Fc) region	189:227	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	5	48	theme	branched	911:918	arg1	N-glycans					920:928	more branched N-glycans	906:928	more branched N-glycans	906:928	However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached.
34192331	2	49	theme	Previous	230:237	arg1	studies					239:245	Previous studies	230:245	Previous studies	230:245	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	0	50	with	activities	27:36	arg1	N-glycans					105:113	multibranched complex-type N-glycans	78:113	multibranched complex-type N-glycans	78:113	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	7	51	from	N-glycans	1065:1073	arg1	region					1085:1090	the Fc region	1078:1090	the Fc region	1078:1090	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	0	52	theme	antibodies	62:71	arg1	Preparation					0:10	Preparation	0:10	Preparation	0:10	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	0	52	theme	antibodies	62:71	arg1	activities					27:36	biological activities	16:36	biological activities	16:36	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	1	53	gly	N-glycosylation	155:169	arg2	Asn297					179:184	Asn297	179:184	Asn297	179:184	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	1	53	gly	N-glycosylation	155:169	arg2	site					171:174	a conserved N-glycosylation site	143:174	a conserved N-glycosylation site at Asn297	143:184	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	5	54	theme	tri-antennary	792:804	arg1	N-glycans					819:827	tri-antennary complex-type N-glycans	792:827	tri-antennary complex-type N-glycans	792:827	However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached.
34192331	8	55	gly	sialylated	1379:1388	arg1	structure					1406:1414	a sialylated penta-antennary structure	1377:1414	a sialylated penta-antennary structure	1377:1414	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	2	56	theme	effector	333:340	arg1	cytotoxicity					389:400	antibody-dependent cellular cytotoxicity	361:400	antibody-dependent cellular cytotoxicity	361:400	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	2	56	theme	effector	333:340	arg1	functions					342:350	the antibody's effector functions	318:350	the antibody's effector functions	318:350	Previous studies have shown that N-glycosylation of this site is a critical mediator of the antibody's effector functions, such as antibody-dependent cellular cytotoxicity.
34192331	0	57	theme	monoclonal	51:60	arg1	antibodies					62:71	anti-HER2 monoclonal antibodies	41:71	anti-HER2 monoclonal antibodies	41:71	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	9	58	theme	IgGs	1480:1483	arg1	majority					1468:1475	the majority	1464:1475	the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region	1464:1542	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	9	59	from	N-glycans	1515:1523	arg1	region					1537:1542	their Fc region	1528:1542	their Fc region	1528:1542	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	7	60	with	combination	1117:1127	arg1	glycosyltransferases					1236:1255	glycosyltransferases	1236:1255	glycosyltransferases	1236:1255	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	4	61	gly	glycoforms	615:624	arg1	N-glycans					633:641	the N-glycans	629:641	the N-glycans on the IgG-Fc region	629:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	0	62	with	Preparation	0:10	arg1	N-glycans					105:113	multibranched complex-type N-glycans	78:113	multibranched complex-type N-glycans	78:113	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	9	63	theme	tri-	1490:1493	arg1	N-glycans					1515:1523	tri- and tetra-antennary N-glycans	1490:1523	tri- and tetra-antennary N-glycans on their Fc region	1490:1542	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	7	64	with	reactions	1221:1229	arg1	glycosyltransferases					1236:1255	glycosyltransferases	1236:1255	glycosyltransferases	1236:1255	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	7	65	theme	multibranched	1051:1063	arg1	N-glycans					1065:1073	multibranched N-glycans	1051:1073	multibranched N-glycans on the Fc region	1051:1090	In this study, IgGs with multibranched N-glycans on the Fc region were prepared by using a combination of the glycosynthase/oxazoline substrate-based N-glycan remodeling technique and successive reactions with glycosyltransferases.
34192331	5	66	with	IgGs	782:785	arg1	N-glycans					819:827	tri-antennary complex-type N-glycans	792:827	tri-antennary complex-type N-glycans	792:827	However, IgGs with tri-antennary complex-type N-glycans have been generated using the N-glycan remodeling technique, suggesting that more branched N-glycans might be artificially attached.
34192331	8	67	theme	penta-antennary	1390:1404	arg1	structure					1406:1414	a sialylated penta-antennary structure	1377:1414	a sialylated penta-antennary structure	1377:1414	Among the IgGs produced by these methods, the largest N-glycan attached was a bisecting N-acetylglucosamine containing a sialylated penta-antennary structure.
34192331	0	68	theme	multibranched	78:90	arg1	N-glycans					105:113	multibranched complex-type N-glycans	78:113	multibranched complex-type N-glycans	78:113	Preparation and biological activities of anti-HER2 monoclonal antibodies with multibranched complex-type N-glycans.
34192331	9	69	theme	bi-antennary	1592:1603	arg1	N-glycans					1605:1613	ordinary bi-antennary N-glycans	1583:1613	ordinary bi-antennary N-glycans	1583:1613	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	4	70	theme	IgG-Fc	650:655	arg1	region					657:662	the IgG-Fc region	646:662	the IgG-Fc region	646:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	1	71	theme	conserved	145:153	arg1	site					171:174	a conserved N-glycosylation site	143:174	a conserved N-glycosylation site at Asn297	143:184	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	4	72	theme	bi-antennary	668:679	arg1	glycoforms					615:624	The major glycoforms	605:624	The major glycoforms of the N-glycans on the IgG-Fc region	605:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	4	72	theme	bi-antennary	668:679	arg1	N-glycans					694:702	bi-antennary complex-type N-glycans	668:702	bi-antennary complex-type N-glycans	668:702	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	9	73	theme	tetra-antennary	1499:1513	arg1	N-glycans					1515:1523	tri- and tetra-antennary N-glycans	1490:1523	tri- and tetra-antennary N-glycans on their Fc region	1490:1542	Concerning the Fc-mediated effector functions, the majority of IgGs with tri- and tetra-antennary N-glycans on their Fc region showed properties similar to IgGs with ordinary bi-antennary N-glycans.
34192331	4	74	from	N-glycans	633:641	arg1	region					657:662	the IgG-Fc region	646:662	the IgG-Fc region	646:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	1	75	from	Asn297	179:184	arg1	site					171:174	a conserved N-glycosylation site	143:174	a conserved N-glycosylation site at Asn297	143:184	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	1	76	theme	N-glycosylation	155:169	arg1	site					171:174	a conserved N-glycosylation site	143:174	a conserved N-glycosylation site at Asn297	143:184	Immunoglobulin G (IgG) has a conserved N-glycosylation site at Asn297 in the fragment crystallizable (Fc) region.
34192331	4	77	theme	N-glycans	633:641	arg1	glycoforms					615:624	The major glycoforms	605:624	The major glycoforms of the N-glycans on the IgG-Fc region	605:662	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
34192331	4	77	theme	N-glycans	633:641	arg1	N-glycans					694:702	bi-antennary complex-type N-glycans	668:702	bi-antennary complex-type N-glycans	668:702	The major glycoforms of the N-glycans on the IgG-Fc region are bi-antennary complex-type N-glycans, while multibranched complex-type N-glycans are not typically found.
31931833	6	0	theme	Endo-T	1118:1123	arg1	location					1106:1113	the location	1102:1113	the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane,	1102:1219	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	5	1	theme	high-mannose	1049:1060	arg1	N-glycans					1067:1075	high-mannose type N-glycans	1049:1075	high-mannose type N-glycans	1049:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	4	2	theme	expression	671:680	arg1	systems					682:688	mammalian cell expression systems	656:688	mammalian cell expression systems	656:688	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	3	3	theme	homogeneous	392:402	arg1	N-glycoproteins					404:418	Thus homogeneous N-glycoproteins	387:418	Thus homogeneous N-glycoproteins with defined N-glycans	387:441	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	0	4	from	production	12:21	arg1	pastoris					86:93	Pichia pastoris	79:93	Pichia pastoris	79:93	Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris.
31931833	5	5	theme	type	1062:1065	arg1	N-glycans					1067:1075	high-mannose type N-glycans	1049:1075	high-mannose type N-glycans	1049:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	4	6	theme	cell	666:669	arg1	systems					682:688	mammalian cell expression systems	656:688	mammalian cell expression systems	656:688	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	1	7	gly	glycoproteins	119:131	arg1	glycoproteins					119:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals.
31931833	4	8	theme	high	594:597	arg1	costs					610:614	the high production costs	590:614	the high production costs induced by the universal utilization of mammalian cell expression systems	590:688	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	5	9	theme	recombinant	926:936	arg1	proteins					938:945	truncated N-GlcNAc-modified recombinant proteins	898:945	truncated N-GlcNAc-modified recombinant proteins	898:945	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	8	10	theme	yeast	1547:1551	arg1	system					1564:1569	a simple glycoengineered yeast expression system	1522:1569	a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures	1522:1673	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	8	11	theme	glycoengineered	1531:1545	arg1	system					1564:1569	a simple glycoengineered yeast expression system	1522:1569	a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures	1522:1673	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	9	12	theme	drugs	1778:1782	arg1	production					1734:1743	mass production	1729:1743	mass production of increasing novel glycoprotein drugs	1729:1782	This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
31931833	9	13	theme	mass	1729:1732	arg1	production					1734:1743	mass production	1729:1743	mass production of increasing novel glycoprotein drugs	1729:1782	This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
31931833	5	14	contain	possesses	1000:1008	arg1	Endo-T					986:991	Endo-T	986:991	Endo-T	986:991	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	5	14	contain	possesses	1000:1008	arg2	activities					1030:1039	powerful hydrolytic activities	1010:1039	powerful hydrolytic activities towards high-mannose type N-glycans	1010:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	5	14	contain	possesses	1000:1008	arg1	isoform					977:983	an ENGase isoform	967:983	an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans	967:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	2	15	theme	serum	341:345	arg1	half-lives					347:356	serum half-lives	341:356	serum half-lives	341:356	N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies.
31931833	4	16	theme	systems	682:688	arg1	utilization					641:651	the universal utilization	627:651	the universal utilization of mammalian cell expression systems	627:688	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	3	17	theme	defined	425:431	arg1	N-glycans					433:441	defined N-glycans	425:441	defined N-glycans	425:441	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	4	18	theme	homogeneous	559:569	arg1	N-glycans					571:579	homogeneous N-glycans	559:579	homogeneous N-glycans	559:579	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	8	19	theme	different	1645:1653	arg1	structures					1664:1673	different N-glycan structures	1645:1673	different N-glycan structures	1645:1673	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	6	20	theme	cell	1206:1209	arg1	membrane					1211:1218	cell membrane	1206:1218	cell membrane	1206:1218	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	1	21	theme	biopharmaceuticals	196:213	arg1	market					186:191	the market	182:191	the market of biopharmaceuticals	182:213	BACKGROUND Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals.
31931833	6	22	theme	subcellular	1138:1148	arg1	membrane					1211:1218	cell membrane	1206:1218	cell membrane	1206:1218	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	22	theme	subcellular	1138:1148	arg1	Golgi					1197:1201	Golgi	1197:1201	Golgi	1197:1201	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	22	theme	subcellular	1138:1148	arg1	reticulum					1181:1189	Endoplasmic reticulum	1169:1189	Endoplasmic reticulum (ER)	1169:1194	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	22	theme	subcellular	1138:1148	arg1	fractions					1150:1158	different subcellular fractions	1128:1158	different subcellular fractions	1128:1158	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	3	23	from	application	466:476	arg1	therapeutics					488:499	clinic therapeutics	481:499	clinic therapeutics	481:499	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	3	23	from	application	466:476	arg1	essential					447:455	essential	447:455	essential	447:455	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	5	24	theme	truncated	898:906	arg1	proteins					938:945	truncated N-GlcNAc-modified recombinant proteins	898:945	truncated N-GlcNAc-modified recombinant proteins	898:945	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	7	25	from	modification	1414:1425	arg1	Asn297					1444:1449	the glycosite Asn297	1430:1449	the glycosite Asn297	1430:1449	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	1	26	theme	BACKGROUND	96:105	arg1	glycoproteins					119:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals.
31931833	7	27	theme	IgG1-Fc	1314:1320	arg1	region					1322:1327	the secreted IgG1-Fc region	1301:1327	the secreted IgG1-Fc region	1301:1327	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	7	28	theme	secreted	1305:1312	arg1	region					1322:1327	the secreted IgG1-Fc region	1301:1327	the secreted IgG1-Fc region	1301:1327	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	1	29	from	position	170:177	arg1	market					186:191	the market	182:191	the market of biopharmaceuticals	182:213	BACKGROUND Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals.
31931833	1	30	theme	Therapeutic	107:117	arg1	glycoproteins					119:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals.
31931833	5	31	theme	powerful	1010:1017	arg1	activities					1030:1039	powerful hydrolytic activities	1010:1039	powerful hydrolytic activities towards high-mannose type N-glycans	1010:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	0	32	theme	Homogeneous	0:10	arg1	production					12:21	Homogeneous production	0:21	Homogeneous production	0:21	Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris.
31931833	6	33	theme	different	1128:1136	arg1	membrane					1211:1218	cell membrane	1206:1218	cell membrane	1206:1218	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	33	theme	different	1128:1136	arg1	Golgi					1197:1201	Golgi	1197:1201	Golgi	1197:1201	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	33	theme	different	1128:1136	arg1	reticulum					1181:1189	Endoplasmic reticulum	1169:1189	Endoplasmic reticulum (ER)	1169:1194	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	33	theme	different	1128:1136	arg1	fractions					1150:1158	different subcellular fractions	1128:1158	different subcellular fractions	1128:1158	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	8	34	theme	N-glycan	1655:1662	arg1	structures					1664:1673	different N-glycan structures	1645:1673	different N-glycan structures	1645:1673	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	8	35	theme	simple	1524:1529	arg1	system					1564:1569	a simple glycoengineered yeast expression system	1522:1569	a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures	1522:1673	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	9	36	theme	novel	1759:1763	arg1	drugs					1778:1782	increasing novel glycoprotein drugs	1748:1782	increasing novel glycoprotein drugs	1748:1782	This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
31931833	5	37	theme	hydrolytic	1019:1028	arg1	activities					1030:1039	powerful hydrolytic activities	1010:1039	powerful hydrolytic activities towards high-mannose type N-glycans	1010:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	4	38	theme	universal	631:639	arg1	utilization					641:651	the universal utilization	627:651	the universal utilization of mammalian cell expression systems	627:688	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	2	39	theme	biological	362:371	arg1	efficiencies					373:384	biological efficiencies	362:384	biological efficiencies	362:384	N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies.
31931833	5	40	theme	ENGase	970:975	arg1	Endo-T					986:991	Endo-T	986:991	Endo-T	986:991	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	5	40	theme	ENGase	970:975	arg1	isoform					977:983	an ENGase isoform	967:983	an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans	967:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	4	41	theme	mammalian	656:664	arg1	systems					682:688	mammalian cell expression systems	656:688	mammalian cell expression systems	656:688	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	7	42	theme	Mass	1469:1472	arg1	Spectrometry					1474:1485	Mass Spectrometry	1469:1485	Mass Spectrometry	1469:1485	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	0	43	theme	recombinant	47:57	arg1	N-GlcNAc-protein					59:74	recombinant N-GlcNAc-protein	47:74	recombinant N-GlcNAc-protein	47:74	Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris.
31931833	9	44	theme	increasing	1748:1757	arg1	drugs					1778:1782	increasing novel glycoprotein drugs	1748:1782	increasing novel glycoprotein drugs	1748:1782	This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
31931833	4	45	theme	several	530:536	arg1	obstacles					538:546	several obstacles	530:546	several obstacles	530:546	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	8	46	dep	CONCLUSION	1488:1497	arg1	develops					1513:1520	develops	1513:1520	develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures	1513:1673	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	9	47	theme	prospective	1704:1714	arg1	platform					1716:1723	a prospective platform	1702:1723	a prospective platform for mass production of increasing novel glycoprotein drugs	1702:1782	This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
31931833	5	48	theme	N-GlcNAc-modified	908:924	arg1	proteins					938:945	truncated N-GlcNAc-modified recombinant proteins	898:945	truncated N-GlcNAc-modified recombinant proteins	898:945	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	5	49	theme	Pichia	831:836	arg1	pastoris					838:845	Pichia pastoris	831:845	a Pichia pastoris (Komagataella phaffii) expression system	829:886	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	2	50	theme	optimal	278:284	arg1	conformations					286:298	optimal conformations	278:298	optimal conformations	278:298	N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies.
31931833	4	51	theme	production	599:608	arg1	costs					610:614	the high production costs	590:614	the high production costs induced by the universal utilization of mammalian cell expression systems	590:688	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	4	52	theme	N-glycosylation	737:751	arg1	microheterogeneities					753:772	the N-glycosylation microheterogeneities	733:772	the N-glycosylation microheterogeneities	733:772	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	3	53	theme	clinic	481:486	arg1	therapeutics					488:499	clinic therapeutics	481:499	clinic therapeutics	481:499	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	5	54	theme	pastoris	838:845	arg1	system					881:886	a Pichia pastoris (Komagataella phaffii) expression system	829:886	a Pichia pastoris (Komagataella phaffii) expression system	829:886	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	7	55	gly	glycosite	1434:1442	arg2	glycosite					1434:1442	the glycosite Asn297	1430:1449	the glycosite Asn297	1430:1449	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	3	56	from	essential	447:455	arg1	application					466:476	their application	460:476	their application in clinic therapeutics	460:499	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	8	57	theme	N-GlcNAc	1582:1589	arg1	proteins					1600:1607	N-GlcNAc modified proteins	1582:1607	N-GlcNAc modified proteins	1582:1607	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	6	58	from	location	1106:1113	arg1	membrane					1211:1218	cell membrane	1206:1218	cell membrane	1206:1218	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	58	from	location	1106:1113	arg1	Golgi					1197:1201	Golgi	1197:1201	Golgi	1197:1201	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	58	from	location	1106:1113	arg1	reticulum					1181:1189	Endoplasmic reticulum	1169:1189	Endoplasmic reticulum (ER)	1169:1194	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	58	from	location	1106:1113	arg1	fractions					1150:1158	different subcellular fractions	1128:1158	different subcellular fractions	1128:1158	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	1	59	used	occupied	138:145	arg2	glycoproteins					119:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins	96:131	BACKGROUND Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals.
31931833	0	60	theme	N-GlcNAc-protein	59:74	arg1	characterization					27:42	characterization	27:42	characterization	27:42	Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris.
31931833	0	60	theme	N-GlcNAc-protein	59:74	arg1	production					12:21	Homogeneous production	0:21	Homogeneous production	0:21	Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris.
31931833	3	61	gly	N-glycoproteins	404:418	arg1	N-glycoproteins					404:418	Thus homogeneous N-glycoproteins	387:418	Thus homogeneous N-glycoproteins with defined N-glycans	387:441	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	4	62	dep	structures	718:727	arg1	the					691:693	the	691:693	the	691:693	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	7	63	theme	glycosite	1434:1442	arg1	Asn297					1444:1449	the glycosite Asn297	1430:1449	the glycosite Asn297	1430:1449	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	9	64	gly	glycoprotein	1765:1776	arg1	glycoprotein					1765:1776	increasing novel glycoprotein drugs	1748:1782	increasing novel glycoprotein drugs	1748:1782	This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
31931833	5	65	dep	pastoris	838:845	arg1	phaffii					861:867	Komagataella phaffii	848:867	Komagataella phaffii	848:867	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	2	66	theme	structural	317:326	arg1	stabilities					328:338	their structural stabilities	311:338	their structural stabilities	311:338	N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies.
31931833	5	67	theme	expression	870:879	arg1	system					881:886	a Pichia pastoris (Komagataella phaffii) expression system	829:886	a Pichia pastoris (Komagataella phaffii) expression system	829:886	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	1	68	theme	important	160:168	arg1	position					170:177	an extremely important position	147:177	an extremely important position in the market of biopharmaceuticals	147:213	BACKGROUND Therapeutic glycoproteins have occupied an extremely important position in the market of biopharmaceuticals.
31931833	8	69	theme	expression	1553:1562	arg1	system					1564:1569	a simple glycoengineered yeast expression system	1522:1569	a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures	1522:1673	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	4	70	theme	non-humanized	695:707	arg1	structures					718:727	non-humanized N-glycan structures	695:727	non-humanized N-glycan structures	695:727	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
31931833	2	71	theme	drugs	243:247	arg1	N-Glycosylation					216:230	N-Glycosylation	216:230	N-Glycosylation of protein drugs	216:247	N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies.
31931833	8	72	theme	modified	1591:1598	arg1	proteins					1600:1607	N-GlcNAc modified proteins	1582:1607	N-GlcNAc modified proteins	1582:1607	CONCLUSION This strategy develops a simple glycoengineered yeast expression system to produce N-GlcNAc modified proteins, which could be further extended to different N-glycan structures.
31931833	7	73	theme	N-GlcNAc	1405:1412	arg1	modification					1414:1425	the N-GlcNAc modification	1401:1425	the N-GlcNAc modification on the glycosite Asn297	1401:1449	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	2	74	theme	protein	235:241	arg1	drugs					243:247	protein drugs	235:247	protein drugs	235:247	N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies.
31931833	3	75	with	N-glycoproteins	404:418	arg1	N-glycans					433:441	defined N-glycans	425:441	defined N-glycans	425:441	Thus homogeneous N-glycoproteins with defined N-glycans are essential in their application in clinic therapeutics.
31931833	5	76	dep	RESULTS	791:797	arg1	constructed					817:827	constructed	817:827	constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans	817:1075	RESULTS In this study, we constructed a Pichia pastoris (Komagataella phaffii) expression system producing truncated N-GlcNAc-modified recombinant proteins through introducing an ENGase isoform (Endo-T) which possesses powerful hydrolytic activities towards high-mannose type N-glycans.
31931833	7	77	theme	truncated	1377:1385	arg1	N-glycans					1387:1395	almost completely truncated N-glycans	1359:1395	almost completely truncated N-glycans	1359:1395	When the Endo-T was expressed in Golgi, the secreted IgG1-Fc region was efficiently produced with almost completely truncated N-glycans and the N-GlcNAc modification on the glycosite Asn297 was confirmed via Mass Spectrometry.
31931833	6	78	theme	Endoplasmic	1169:1179	arg1	ER					1192:1193	ER	1192:1193	ER	1192:1193	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	6	78	theme	Endoplasmic	1169:1179	arg1	reticulum					1181:1189	Endoplasmic reticulum	1169:1189	Endoplasmic reticulum (ER)	1169:1194	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	0	79	theme	Pichia	79:84	arg1	pastoris					86:93	Pichia pastoris	79:93	Pichia pastoris	79:93	Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris.
31931833	0	80	from	characterization	27:42	arg1	pastoris					86:93	Pichia pastoris	79:93	Pichia pastoris	79:93	Homogeneous production and characterization of recombinant N-GlcNAc-protein in Pichia pastoris.
31931833	9	81	theme	glycoprotein	1765:1776	arg1	drugs					1778:1782	increasing novel glycoprotein drugs	1748:1782	increasing novel glycoprotein drugs	1748:1782	This system would provide a prospective platform for mass production of increasing novel glycoprotein drugs.
31931833	6	82	theme	hydrolytic	1236:1245	arg1	efficiencies					1247:1258	their hydrolytic efficiencies	1230:1258	their hydrolytic efficiencies	1230:1258	The results showed that the location of Endo-T in different subcellular fractions, such as Endoplasmic reticulum (ER), Golgi or cell membrane, affected their hydrolytic efficiencies.
31931833	2	83	gly	N-Glycosylation	216:230	arg1	drugs					243:247	protein drugs	235:247	protein drugs	235:247	N-Glycosylation of protein drugs facilitates them to maintain optimal conformations and affect their structural stabilities, serum half-lives and biological efficiencies.
31931833	4	84	theme	N-glycan	709:716	arg1	structures					718:727	non-humanized N-glycan structures	695:727	non-humanized N-glycan structures	695:727	However, there still remain several obstacles to acquire homogeneous N-glycans, such as the high production costs induced by the universal utilization of mammalian cell expression systems, the non-humanized N-glycan structures and the N-glycosylation microheterogeneities between batches.
33383989	4	0	theme	differentiation	882:896	arg1	procedure					898:906	an optimized, large-scale differentiation procedure	856:906	procedure	898:906	For in vitro adipogenesis, ADSCs were adipogenically differentiated in cell culture using an optimized, large-scale differentiation procedure.
33383989	10	1	theme	rare	1885:1888	arg1	termini					1907:1913	rare β-linked Gal-Gal termini	1885:1913	rare β-linked Gal-Gal termini	1885:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33383989	6	2	dep	adipocytes	1290:1299	arg1	%					1306:1306	32.1%	1302:1306	32.1% of total glycans	1302:1323	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	2	dep	adipocytes	1290:1299	arg1	glycans					1317:1323	total glycans	1311:1323	total glycans	1311:1323	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	9	3	from	increase	1803:1810	arg1	transcript					1825:1834	Fut8 gene transcript	1815:1834	Fut8 gene transcript	1815:1834	Core fucosylation was also significantly increased during in vivo adipogenesis but did not correlate with an increase in Fut8 gene transcript.
33383989	11	4	theme	GlcNAc	2076:2081	arg1	feature					2115:2121	a characteristic feature	2098:2121	a characteristic feature of human adipocyte membrane protein N-glycosylation	2098:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	11	4	theme	GlcNAc	2076:2081	arg1	structures					2083:2092	bisecting GlcNAc structures	2066:2092	bisecting GlcNAc structures	2066:2092	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	8	5	located	found	1570:1574	arg2	structures					1554:1563	The bisecting GlcNAc structures	1533:1563	The bisecting GlcNAc structures	1533:1563	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	8	5	located	found	1570:1574	arg1	majority					1583:1590	the majority	1579:1590	the majority of human native adipocyte membrane proteins	1579:1634	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	8	6	theme	native	1601:1606	arg1	proteins					1627:1634	human native adipocyte membrane proteins	1595:1634	human native adipocyte membrane proteins	1595:1634	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	3	7	theme	same	713:716	arg1	individuals					718:728	the same individuals	709:728	the same individuals	709:728	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	6	8	theme	mature	1283:1288	arg1	adipocytes					1290:1299	mature adipocytes	1283:1299	mature adipocytes (32.1% of total glycans)	1283:1324	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	11	9	theme	progeny	1997:2003	arg1	profiles					1957:1964	the N-glycan profiles	1944:1964	the N-glycan profiles of the in vitro differentiated progeny	1944:2003	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	8	10	theme	human	1669:1673	arg1	biology					1685:1691	human adipocyte biology	1669:1691	human adipocyte biology	1669:1691	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	12	11	dep	GlycoPOST	2206:2214	arg1	ID					2217:2218	ID	2217:2218	ID: GPST000153 https://glycopost.glycosmos.org/	2217:2263	Raw MS files are available on GlycoPOST (ID: GPST000153 https://glycopost.glycosmos.org/).
33383989	1	12	contain	contains	103:110	arg2	source					120:125	a major source	112:125	a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types	112:226	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	12	contain	contains	103:110	arg1	tissue					96:101	Human adipose tissue	82:101	Human adipose tissue	82:101	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	11	13	theme	characteristic	2100:2113	arg1	feature					2115:2121	a characteristic feature	2098:2121	a characteristic feature of human adipocyte membrane protein N-glycosylation	2098:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	11	13	theme	characteristic	2100:2113	arg1	structures					2083:2092	bisecting GlcNAc structures	2066:2092	bisecting GlcNAc structures	2066:2092	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	6	14	theme	ionization	1161:1170	arg1	spectrometry					1177:1188	negative-ion electrospray ionization mass spectrometry	1135:1188	negative-ion electrospray ionization mass spectrometry (ESI-MS)	1135:1197	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	14	theme	ionization	1161:1170	arg1	ESI-MS					1191:1196	ESI-MS	1191:1196	ESI-MS	1191:1196	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	2	15	theme	human	558:562	arg1	differentiation					580:594	human ADSC adipogenic differentiation	558:594	human ADSC adipogenic differentiation	558:594	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	6	16	theme	N-glycans	1256:1264	arg1	levels					1224:1229	Significantly higher levels	1203:1229	Significantly higher levels of bisecting GlcNAc-type N-glycans	1203:1264	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	11	17	theme	native	2021:2026	arg1	adipocytes					2028:2037	native adipocytes	2021:2037	native adipocytes	2021:2037	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	2	18	theme	protein	529:535	arg1	glycosylation					537:549	protein glycosylation	529:549	protein glycosylation	529:549	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	6	19	theme	negative-ion	1135:1146	arg1	spectrometry					1177:1188	negative-ion electrospray ionization mass spectrometry	1135:1188	negative-ion electrospray ionization mass spectrometry (ESI-MS)	1135:1197	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	19	theme	negative-ion	1135:1146	arg1	ESI-MS					1191:1196	ESI-MS	1191:1196	ESI-MS	1191:1196	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	3	20	from	individuals	718:728	arg1	ADSCs					698:702	ADSCs	698:702	ADSCs from the same individuals	698:728	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	6	21	theme	GlcNAc-type	1244:1254	arg1	N-glycans					1256:1264	bisecting GlcNAc-type N-glycans	1234:1264	bisecting GlcNAc-type N-glycans	1234:1264	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	3	22	theme	adipogenesis	752:763	arg1	model					735:739	a model	733:739	a model of in vivo adipogenesis	733:763	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	3	22	theme	adipogenesis	752:763	arg1	glycosylation					647:659	the global membrane protein glycosylation	619:659	the global membrane protein glycosylation of native adipocytes	619:680	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	11	23	theme	adipocyte	2132:2140	arg1	N-glycosylation					2159:2173	human adipocyte membrane protein N-glycosylation	2126:2173	human adipocyte membrane protein N-glycosylation	2126:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	1	24	theme	various	209:215	arg1	types					222:226	various cell types	209:226	various cell types	209:226	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	6	25	dep	in	1333:1334	arg1	vitro					1336:1340	vitro	1336:1340	vitro	1336:1340	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	2	26	theme	ADSC	564:567	arg1	differentiation					580:594	human ADSC adipogenic differentiation	558:594	human ADSC adipogenic differentiation	558:594	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	3	27	theme	in	744:745	arg1	adipogenesis					752:763	in vivo adipogenesis	744:763	in vivo adipogenesis	744:763	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	6	28	theme	total	1311:1315	arg1	glycans					1317:1323	total glycans	1311:1323	total glycans	1311:1323	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	5	29	theme	membrane	913:920	arg1	glycome					922:928	The membrane glycome	909:928	The membrane glycome of the differentiated ADSCs (dADSCs)	909:965	The membrane glycome of the differentiated ADSCs (dADSCs) was compared with mature adipocytes and the progenitor ADSCs.
33383989	6	30	theme	higher	1217:1222	arg1	levels					1224:1229	Significantly higher levels	1203:1229	Significantly higher levels of bisecting GlcNAc-type N-glycans	1203:1264	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	1	31	theme	stem	146:149	arg1	ADSCs					158:162	ADSCs	158:162	ADSCs	158:162	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	31	theme	stem	146:149	arg1	cells					151:155	adipose-derived stem cells	130:155	adipose-derived stem cells (ADSCs)	130:163	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	11	32	theme	bisecting	2066:2074	arg1	feature					2115:2121	a characteristic feature	2098:2121	a characteristic feature of human adipocyte membrane protein N-glycosylation	2098:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	11	32	theme	bisecting	2066:2074	arg1	structures					2083:2092	bisecting GlcNAc structures	2066:2092	bisecting GlcNAc structures	2066:2092	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	0	33	theme	Adipogenesis	68:79	arg1	Characteristic					44:57	Characteristic	44:57	Characteristic of Human Adipogenesis	44:79	Bisecting GlcNAc Protein N-Glycosylation Is Characteristic of Human Adipogenesis.
33383989	3	34	theme	present	604:610	arg1	study					612:616	the present study	600:616	the present study	600:616	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	2	35	theme	adipogenic	569:578	arg1	differentiation					580:594	human ADSC adipogenic differentiation	558:594	human ADSC adipogenic differentiation	558:594	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	9	36	theme	in	1752:1753	arg1	adipogenesis					1760:1771	in vivo adipogenesis	1752:1771	in vivo adipogenesis	1752:1771	Core fucosylation was also significantly increased during in vivo adipogenesis but did not correlate with an increase in Fut8 gene transcript.
33383989	3	37	dep	in	744:745	arg1	vivo					747:750	vivo	747:750	vivo	747:750	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	6	38	dep	progeny	1348:1354	arg1	%					1360:1360	1.9%	1357:1360	1.9% of total glycans	1357:1377	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	38	dep	progeny	1348:1354	arg1	glycans					1371:1377	total glycans	1365:1377	total glycans	1365:1377	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	39	located	detected	1271:1278	arg1	adipocytes					1290:1299	mature adipocytes	1283:1299	mature adipocytes (32.1% of total glycans)	1283:1324	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	39	located	detected	1271:1278	arg2	levels					1224:1229	Significantly higher levels	1203:1229	Significantly higher levels of bisecting GlcNAc-type N-glycans	1203:1264	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	7	40	theme	structural	1516:1525	arg1	type					1527:1530	this structural type	1511:1530	this structural type	1511:1530	This was further correlated by the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type.
33383989	1	41	theme	adipose	88:94	arg1	tissue					96:101	Human adipose tissue	82:101	Human adipose tissue	82:101	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	11	42	theme	protein	2151:2157	arg1	N-glycosylation					2159:2173	human adipocyte membrane protein N-glycosylation	2126:2173	human adipocyte membrane protein N-glycosylation	2126:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	8	43	from	role	1661:1664	arg1	biology					1685:1691	human adipocyte biology	1669:1691	human adipocyte biology	1669:1691	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	0	44	theme	Bisecting	0:8	arg1	N-Glycosylation					25:39	Bisecting GlcNAc Protein N-Glycosylation	0:39	Bisecting GlcNAc Protein N-Glycosylation	0:39	Bisecting GlcNAc Protein N-Glycosylation Is Characteristic of Human Adipogenesis.
33383989	5	45	theme	differentiated	937:950	arg1	ADSCs					952:956	the differentiated ADSCs	933:956	the differentiated ADSCs (dADSCs)	933:965	The membrane glycome of the differentiated ADSCs (dADSCs) was compared with mature adipocytes and the progenitor ADSCs.
33383989	5	45	theme	differentiated	937:950	arg1	dADSCs					959:964	dADSCs	959:964	dADSCs	959:964	The membrane glycome of the differentiated ADSCs (dADSCs) was compared with mature adipocytes and the progenitor ADSCs.
33383989	6	46	theme	glycan	1044:1049	arg1	structures					1051:1060	137 glycan structures	1040:1060	137 glycan structures	1040:1060	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	2	47	theme	cell	413:416	arg1	differentiation					418:432	stem cell differentiation	408:432	stem cell differentiation	408:432	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	0	48	theme	Protein	17:23	arg1	N-Glycosylation					25:39	Bisecting GlcNAc Protein N-Glycosylation	0:39	Bisecting GlcNAc Protein N-Glycosylation	0:39	Bisecting GlcNAc Protein N-Glycosylation Is Characteristic of Human Adipogenesis.
33383989	1	49	theme	mesenchymal	268:278	arg1	adipocytes					299:308	adipocytes	299:308	adipocytes	299:308	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	49	theme	mesenchymal	268:278	arg1	lineages					280:287	mesenchymal lineages	268:287	mesenchymal lineages including adipocytes	268:308	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	50	theme	major	114:118	arg1	source					120:125	a major source	112:125	a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types	112:226	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	3	51	theme	protein	639:645	arg1	model					735:739	a model	733:739	a model of in vivo adipogenesis	733:763	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	3	51	theme	protein	639:645	arg1	glycosylation					647:659	the global membrane protein glycosylation	619:659	the global membrane protein glycosylation of native adipocytes	619:680	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	12	52	theme	Raw	2176:2178	arg1	files					2183:2187	Raw MS files	2176:2187	Raw MS files	2176:2187	Raw MS files are available on GlycoPOST (ID: GPST000153 https://glycopost.glycosmos.org/).
33383989	5	53	theme	progenitor	1011:1020	arg1	ADSCs					1022:1026	the progenitor ADSCs	1007:1026	the progenitor ADSCs	1007:1026	The membrane glycome of the differentiated ADSCs (dADSCs) was compared with mature adipocytes and the progenitor ADSCs.
33383989	1	54	link	adipose-derived	130:144	arg1	ADSCs					158:162	ADSCs	158:162	ADSCs	158:162	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	54	link	adipose-derived	130:144	arg1	cells					151:155	adipose-derived stem cells	130:155	adipose-derived stem cells (ADSCs)	130:163	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	3	55	theme	global	623:628	arg1	model					735:739	a model	733:739	a model of in vivo adipogenesis	733:763	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	3	55	theme	global	623:628	arg1	glycosylation					647:659	the global membrane protein glycosylation	619:659	the global membrane protein glycosylation of native adipocytes	619:680	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	6	56	theme	glycans	1371:1377	arg1	%					1360:1360	1.9%	1357:1360	1.9% of total glycans	1357:1377	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	56	theme	glycans	1371:1377	arg1	glycans					1371:1377	total glycans	1365:1377	total glycans	1365:1377	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	7	57	theme	responsible	1468:1478	arg1	gene					1463:1466	the MGAT3 gene	1453:1466	the MGAT3 gene responsible for the enzymatic synthesis of this structural type	1453:1530	This was further correlated by the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type.
33383989	9	58	theme	gene	1820:1823	arg1	transcript					1825:1834	Fut8 gene transcript	1815:1834	Fut8 gene transcript	1815:1834	Core fucosylation was also significantly increased during in vivo adipogenesis but did not correlate with an increase in Fut8 gene transcript.
33383989	8	59	theme	GlcNAc	1547:1552	arg1	structures					1554:1563	The bisecting GlcNAc structures	1533:1563	The bisecting GlcNAc structures	1533:1563	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	3	60	theme	adipocytes	671:680	arg1	model					735:739	a model	733:739	a model of in vivo adipogenesis	733:763	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	3	60	theme	adipocytes	671:680	arg1	glycosylation					647:659	the global membrane protein glycosylation	619:659	the global membrane protein glycosylation of native adipocytes	619:680	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	4	61	theme	in	770:771	arg1	adipogenesis					779:790	in vitro adipogenesis	770:790	in vitro adipogenesis	770:790	For in vitro adipogenesis, ADSCs were adipogenically differentiated in cell culture using an optimized, large-scale differentiation procedure.
33383989	8	62	theme	adipocyte	1608:1616	arg1	proteins					1627:1634	human native adipocyte membrane proteins	1595:1634	human native adipocyte membrane proteins	1595:1634	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	1	63	theme	cell	217:220	arg1	types					222:226	various cell types	209:226	various cell types	209:226	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	7	64	theme	MGAT3	1457:1461	arg1	gene					1463:1466	the MGAT3 gene	1453:1466	the MGAT3 gene responsible for the enzymatic synthesis of this structural type	1453:1530	This was further correlated by the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type.
33383989	5	65	theme	mature	985:990	arg1	adipocytes					992:1001	mature adipocytes	985:1001	mature adipocytes	985:1001	The membrane glycome of the differentiated ADSCs (dADSCs) was compared with mature adipocytes and the progenitor ADSCs.
33383989	8	66	theme	proteins	1627:1634	arg1	majority					1583:1590	the majority	1579:1590	the majority of human native adipocyte membrane proteins	1579:1634	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	3	67	gly	glycosylation	647:659	arg1	study					612:616	the present study	600:616	the present study	600:616	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	3	67	gly	glycosylation	647:659	arg1	adipocytes					671:680	native adipocytes	664:680	native adipocytes	664:680	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	10	68	theme	β-linked	1890:1897	arg1	termini					1907:1913	rare β-linked Gal-Gal termini	1885:1913	rare β-linked Gal-Gal termini	1885:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33383989	6	69	dep	detected	1271:1278	arg1	compared					1380:1387	compared	1380:1387	compared to ADSCs	1380:1396	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	7	70	theme	mRNA	1434:1437	arg1	expression					1439:1448	the mRNA expression	1430:1448	the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type	1430:1530	This was further correlated by the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type.
33383989	11	71	theme	differentiated	1982:1995	arg1	progeny					1997:2003	the in vitro differentiated progeny	1969:2003	the in vitro differentiated progeny	1969:2003	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	8	72	theme	important	1651:1659	arg1	role					1661:1664	an important role	1648:1664	an important role in human adipocyte biology	1648:1691	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	4	73	theme	optimized	859:867	arg1	procedure					898:906	an optimized, large-scale differentiation procedure	856:906	procedure	898:906	For in vitro adipogenesis, ADSCs were adipogenically differentiated in cell culture using an optimized, large-scale differentiation procedure.
33383989	10	74	contain	carrying	1876:1883	arg2	termini					1907:1913	rare β-linked Gal-Gal termini	1885:1913	rare β-linked Gal-Gal termini	1885:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33383989	10	74	contain	carrying	1876:1883	arg1	structures					1865:1874	low abundance structures	1851:1874	low abundance structures carrying rare β-linked Gal-Gal termini	1851:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33383989	8	75	theme	human	1595:1599	arg1	proteins					1627:1634	human native adipocyte membrane proteins	1595:1634	human native adipocyte membrane proteins	1595:1634	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	11	76	theme	in	1973:1974	arg1	progeny					1997:2003	the in vitro differentiated progeny	1969:2003	the in vitro differentiated progeny	1969:2003	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	11	77	theme	human	2126:2130	arg1	N-glycosylation					2159:2173	human adipocyte membrane protein N-glycosylation	2126:2173	human adipocyte membrane protein N-glycosylation	2126:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	6	78	theme	mass	1172:1175	arg1	spectrometry					1177:1188	negative-ion electrospray ionization mass spectrometry	1135:1188	negative-ion electrospray ionization mass spectrometry (ESI-MS)	1135:1197	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	78	theme	mass	1172:1175	arg1	ESI-MS					1191:1196	ESI-MS	1191:1196	ESI-MS	1191:1196	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	8	79	theme	adipocyte	1675:1683	arg1	biology					1685:1691	human adipocyte biology	1669:1691	human adipocyte biology	1669:1691	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	4	80	dep	in	770:771	arg1	vitro					773:777	vitro	773:777	vitro	773:777	For in vitro adipogenesis, ADSCs were adipogenically differentiated in cell culture using an optimized, large-scale differentiation procedure.
33383989	4	81	theme	cell	837:840	arg1	culture					842:848	cell culture	837:848	cell culture using an optimized, large-scale differentiation procedure	837:906	For in vitro adipogenesis, ADSCs were adipogenically differentiated in cell culture using an optimized, large-scale differentiation procedure.
33383989	6	82	theme	electrospray	1148:1159	arg1	spectrometry					1177:1188	negative-ion electrospray ionization mass spectrometry	1135:1188	negative-ion electrospray ionization mass spectrometry (ESI-MS)	1135:1197	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	82	theme	electrospray	1148:1159	arg1	ESI-MS					1191:1196	ESI-MS	1191:1196	ESI-MS	1191:1196	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	83	theme	in	1333:1334	arg1	progeny					1348:1354	in vitro dADSC progeny	1333:1354	in vitro dADSC progeny (1.9% of total glycans)	1333:1378	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	84	theme	bisecting	1234:1242	arg1	N-glycans					1256:1264	bisecting GlcNAc-type N-glycans	1234:1264	bisecting GlcNAc-type N-glycans	1234:1264	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	85	theme	glycans	1317:1323	arg1	%					1306:1306	32.1%	1302:1306	32.1% of total glycans	1302:1323	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	6	85	theme	glycans	1317:1323	arg1	glycans					1317:1323	total glycans	1311:1323	total glycans	1311:1323	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	11	86	dep	in	1973:1974	arg1	vitro					1976:1980	vitro	1976:1980	vitro	1976:1980	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	4	87	theme	large-scale	870:880	arg1	procedure					898:906	an optimized, large-scale differentiation procedure	856:906	procedure	898:906	For in vitro adipogenesis, ADSCs were adipogenically differentiated in cell culture using an optimized, large-scale differentiation procedure.
33383989	10	88	theme	abundance	1855:1863	arg1	structures					1865:1874	low abundance structures	1851:1874	low abundance structures carrying rare β-linked Gal-Gal termini	1851:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33383989	9	89	dep	in	1752:1753	arg1	vivo					1755:1758	vivo	1755:1758	vivo	1755:1758	Core fucosylation was also significantly increased during in vivo adipogenesis but did not correlate with an increase in Fut8 gene transcript.
33383989	1	90	theme	adipose-derived	130:144	arg1	ADSCs					158:162	ADSCs	158:162	ADSCs	158:162	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	90	theme	adipose-derived	130:144	arg1	cells					151:155	adipose-derived stem cells	130:155	adipose-derived stem cells (ADSCs)	130:163	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	6	91	theme	total	1365:1369	arg1	glycans					1371:1377	total glycans	1365:1377	total glycans	1365:1377	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	11	92	theme	N-glycan	1948:1955	arg1	profiles					1957:1964	the N-glycan profiles	1944:1964	the N-glycan profiles of the in vitro differentiated progeny	1944:2003	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	1	93	theme	cells	151:155	arg1	source					120:125	a major source	112:125	a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types	112:226	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	12	94	dep	ID	2217:2218	arg1	//glycopost.glycosmos.org/					2238:2263	//glycopost.glycosmos.org/	2238:2263	ID: GPST000153 https://glycopost.glycosmos.org/	2217:2263	Raw MS files are available on GlycoPOST (ID: GPST000153 https://glycopost.glycosmos.org/).
33383989	12	94	dep	ID	2217:2218	arg1	https					2232:2236	GPST000153 https	2221:2236	ID: GPST000153 https://glycopost.glycosmos.org/	2217:2263	Raw MS files are available on GlycoPOST (ID: GPST000153 https://glycopost.glycosmos.org/).
33383989	7	95	theme	type	1527:1530	arg1	synthesis					1498:1506	the enzymatic synthesis	1484:1506	the enzymatic synthesis of this structural type	1484:1530	This was further correlated by the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type.
33383989	6	96	theme	dADSC	1342:1346	arg1	progeny					1348:1354	in vitro dADSC progeny	1333:1354	in vitro dADSC progeny (1.9% of total glycans)	1333:1378	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	1	97	theme	mature	339:344	arg1	adipocytes					346:355	mature adipocytes	339:355	mature adipocytes	339:355	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	98	theme	Human	82:86	arg1	tissue					96:101	Human adipose tissue	82:101	Human adipose tissue	82:101	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	2	99	theme	therapeutic	484:494	arg1	potential					496:504	their therapeutic potential	478:504	their therapeutic potential	478:504	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	0	100	theme	GlcNAc	10:15	arg1	N-Glycosylation					25:39	Bisecting GlcNAc Protein N-Glycosylation	0:39	Bisecting GlcNAc Protein N-Glycosylation	0:39	Bisecting GlcNAc Protein N-Glycosylation Is Characteristic of Human Adipogenesis.
33383989	6	101	theme	structures	1051:1060	arg1	total					1031:1035	A total	1029:1035	A total of 137 glycan structures	1029:1060	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	11	102	theme	N-glycosylation	2159:2173	arg1	feature					2115:2121	a characteristic feature	2098:2121	a characteristic feature of human adipocyte membrane protein N-glycosylation	2098:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	11	102	theme	N-glycosylation	2159:2173	arg1	structures					2083:2092	bisecting GlcNAc structures	2066:2092	bisecting GlcNAc structures	2066:2092	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	2	103	theme	Protein	358:364	arg1	glycosylation					366:378	Protein glycosylation	358:378	Protein glycosylation	358:378	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	5	104	theme	ADSCs	952:956	arg1	glycome					922:928	The membrane glycome	909:928	The membrane glycome of the differentiated ADSCs (dADSCs)	909:965	The membrane glycome of the differentiated ADSCs (dADSCs) was compared with mature adipocytes and the progenitor ADSCs.
33383989	2	105	theme	stem	408:411	arg1	differentiation					418:432	stem cell differentiation	408:432	stem cell differentiation	408:432	Protein glycosylation has been shown to change in stem cell differentiation, and while ADSCs have been acknowledged for their therapeutic potential, little is known about protein glycosylation during human ADSC adipogenic differentiation.
33383989	3	106	theme	membrane	630:637	arg1	model					735:739	a model	733:739	a model of in vivo adipogenesis	733:763	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	3	106	theme	membrane	630:637	arg1	glycosylation					647:659	the global membrane protein glycosylation	619:659	the global membrane protein glycosylation of native adipocytes	619:680	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	11	107	theme	membrane	2142:2149	arg1	N-glycosylation					2159:2173	human adipocyte membrane protein N-glycosylation	2126:2173	human adipocyte membrane protein N-glycosylation	2126:2173	Overall, the N-glycan profiles of the in vitro differentiated progeny did not reflect native adipocytes, and the results show that bisecting GlcNAc structures are a characteristic feature of human adipocyte membrane protein N-glycosylation.
33383989	8	108	theme	bisecting	1537:1545	arg1	structures					1554:1563	The bisecting GlcNAc structures	1533:1563	The bisecting GlcNAc structures	1533:1563	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	1	109	contain	have	170:173	arg1	source					120:125	a major source	112:125	a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types	112:226	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	1	109	contain	have	170:173	arg2	ability					179:185	the ability to differentiate into various cell types	175:226	the ability to differentiate into various cell types	175:226	Human adipose tissue contains a major source of adipose-derived stem cells (ADSCs) that have the ability to differentiate into various cell types: in vitro, ADSCs can differentiate into mesenchymal lineages including adipocytes, while in vivo, ADSCs become mature adipocytes.
33383989	0	110	theme	Human	62:66	arg1	Adipogenesis					68:79	Human Adipogenesis	62:79	Human Adipogenesis	62:79	Bisecting GlcNAc Protein N-Glycosylation Is Characteristic of Human Adipogenesis.
33383989	7	111	theme	enzymatic	1488:1496	arg1	synthesis					1498:1506	the enzymatic synthesis	1484:1506	the enzymatic synthesis of this structural type	1484:1530	This was further correlated by the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type.
33383989	9	112	theme	Fut8	1815:1818	arg1	transcript					1825:1834	Fut8 gene transcript	1815:1834	Fut8 gene transcript	1815:1834	Core fucosylation was also significantly increased during in vivo adipogenesis but did not correlate with an increase in Fut8 gene transcript.
33383989	3	113	theme	native	664:669	arg1	adipocytes					671:680	native adipocytes	664:680	native adipocytes	664:680	In the present study, the global membrane protein glycosylation of native adipocytes was compared to ADSCs from the same individuals as a model of in vivo adipogenesis.
33383989	12	114	theme	MS	2180:2181	arg1	files					2183:2187	Raw MS files	2176:2187	Raw MS files	2176:2187	Raw MS files are available on GlycoPOST (ID: GPST000153 https://glycopost.glycosmos.org/).
33383989	8	115	theme	membrane	1618:1625	arg1	proteins					1627:1634	human native adipocyte membrane proteins	1595:1634	human native adipocyte membrane proteins	1595:1634	The bisecting GlcNAc structures were found on the majority of human native adipocyte membrane proteins, suggesting an important role in human adipocyte biology.
33383989	9	116	theme	Core	1694:1697	arg1	fucosylation					1699:1710	Core fucosylation	1694:1710	Core fucosylation	1694:1710	Core fucosylation was also significantly increased during in vivo adipogenesis but did not correlate with an increase in Fut8 gene transcript.
33383989	10	117	theme	low	1851:1853	arg1	structures					1865:1874	low abundance structures	1851:1874	low abundance structures carrying rare β-linked Gal-Gal termini	1851:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33383989	10	118	link	β-linked	1890:1897	arg1	termini					1907:1913	rare β-linked Gal-Gal termini	1885:1913	rare β-linked Gal-Gal termini	1885:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33383989	7	119	theme	gene	1463:1466	arg1	expression					1439:1448	the mRNA expression	1430:1448	the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type	1430:1530	This was further correlated by the mRNA expression of the MGAT3 gene responsible for the enzymatic synthesis of this structural type.
33383989	6	120	theme	cell	1098:1101	arg1	types					1103:1107	the three cell types	1088:1107	the three cell types	1088:1107	A total of 137 glycan structures were characterized across the three cell types using PGC-LC coupled with negative-ion electrospray ionization mass spectrometry (ESI-MS)/MS. Significantly higher levels of bisecting GlcNAc-type N-glycans were detected in mature adipocytes (32.1% of total glycans) and in in vitro dADSC progeny (1.9% of total glycans) compared to ADSCs.
33383989	10	121	theme	Gal-Gal	1899:1905	arg1	termini					1907:1913	rare β-linked Gal-Gal termini	1885:1913	rare β-linked Gal-Gal termini	1885:1913	Unexpectedly, low abundance structures carrying rare β-linked Gal-Gal termini were also detected.
33377107	5	0	theme	molecular	653:661	arg1	simulations					672:682	3D molecular dynamics simulations	650:682	3D molecular dynamics simulations of certain glycoproteins alone	650:713	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	1	1	theme	O-linked	186:193	arg1	glycosylation					195:207	O-linked glycosylation	186:207	O-linked glycosylation	186:207	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	4	2	link	O-linked	529:536	arg1	glycoproteins					538:550	N- and/or O-linked glycoproteins	519:550	N- and/or O-linked glycoproteins	519:550	This procedure can be modified and applied to a variety of N- and/or O-linked glycoproteins.
33377107	3	3	theme	glycan	421:426	arg1	assignments					428:438	any glycan assignments	417:438	any glycan assignments	417:438	Glycomics provides structural characterization on any glycan assignments by glycoproteomics.
33377107	6	4	theme	complete	752:759	arg1	details					761:767	complete details	752:767	complete details on the use and execution of this protocol	752:809	For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).
33377107	5	5	gly	glycoproteins	695:707	arg1	glycoproteins					695:707	certain glycoproteins	687:707	certain glycoproteins alone	687:713	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	2	6	theme	glycoproteins	352:364	arg1	microheterogeneity					330:347	site-specific microheterogeneity	316:347	site-specific microheterogeneity of glycoproteins	316:364	Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins.
33377107	2	7	gly	glycoproteins	352:364	arg1	glycoproteins					352:364	glycoproteins	352:364	glycoproteins	352:364	Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins.
33377107	5	8	theme	glycoproteins	695:707	arg1	simulations					672:682	3D molecular dynamics simulations	650:682	3D molecular dynamics simulations of certain glycoproteins alone	650:713	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	0	9	theme	Glycomics-informed	0:17	arg1	analysis					34:41	Glycomics-informed glycoproteomic analysis	0:41	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.	0:102	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.
33377107	1	10	theme	SARS-CoV-2	212:221	arg1	protein					229:235	SARS-CoV-2 spike protein	212:235	SARS-CoV-2 spike protein	212:235	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	0	11	theme	glycoproteomic	19:32	arg1	analysis					34:41	Glycomics-informed glycoproteomic analysis	0:41	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.	0:102	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.
33377107	1	12	theme	spike	223:227	arg1	protein					229:235	SARS-CoV-2 spike protein	212:235	SARS-CoV-2 spike protein	212:235	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	2	13	gly	microheterogeneity	330:347	arg1	glycoproteins					352:364	glycoproteins	352:364	glycoproteins	352:364	Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins.
33377107	1	14	theme	protein	229:235	arg1	N-					179:180	site-specific N-	165:180	site-specific N-	165:180	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	1	14	theme	protein	229:235	arg1	glycosylation					195:207	O-linked glycosylation	186:207	O-linked glycosylation	186:207	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	1	15	link	O-linked	186:193	arg1	glycosylation					195:207	O-linked glycosylation	186:207	O-linked glycosylation	186:207	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	6	16	theme	protocol	802:809	arg1	use					776:778	use	776:778	use	776:778	For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).
33377107	6	16	theme	protocol	802:809	arg1	execution					784:792	execution	784:792	execution	784:792	For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).
33377107	1	17	theme	integrated	131:140	arg1	approach					142:149	an integrated approach	128:149	an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry	128:256	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	1	18	theme	mass	240:243	arg1	spectrometry					245:256	mass spectrometry	240:256	mass spectrometry	240:256	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	0	19	theme	glycosylation	60:72	arg1	analysis					34:41	Glycomics-informed glycoproteomic analysis	0:41	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.	0:102	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.
33377107	4	20	theme	glycoproteins	538:550	arg1	glycoproteins					538:550	N- and/or O-linked glycoproteins	519:550	N- and/or O-linked glycoproteins	519:550	This procedure can be modified and applied to a variety of N- and/or O-linked glycoproteins.
33377107	4	20	theme	glycoproteins	538:550	arg1	variety					508:514	a variety	506:514	a variety of N- and/or O-linked glycoproteins	506:550	This procedure can be modified and applied to a variety of N- and/or O-linked glycoproteins.
33377107	5	21	theme	glycomics-informed	587:604	arg1	glycoproteomics					606:620	the glycomics-informed glycoproteomics	583:620	the glycomics-informed glycoproteomics	583:620	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	5	21	theme	glycomics-informed	587:604	arg1	useful					629:634	useful	629:634	useful	629:634	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	0	22	theme	site-specific	46:58	arg1	glycosylation					60:72	site-specific glycosylation	46:72	site-specific glycosylation	46:72	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.
33377107	2	23	gly	glycopeptides	291:303	arg2	glycopeptides					291:303	intact glycopeptides	284:303	intact glycopeptides	284:303	Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins.
33377107	2	24	theme	intact	284:289	arg1	glycopeptides					291:303	intact glycopeptides	284:303	intact glycopeptides	284:303	Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins.
33377107	5	25	theme	dynamics	663:670	arg1	simulations					672:682	3D molecular dynamics simulations	650:682	3D molecular dynamics simulations of certain glycoproteins alone	650:713	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	0	26	theme	SARS-CoV-2	78:87	arg1	protein					95:101	SARS-CoV-2 spike protein	78:101	SARS-CoV-2 spike protein	78:101	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.
33377107	4	27	theme	N-	519:520	arg1	glycoproteins					538:550	N- and/or O-linked glycoproteins	519:550	N- and/or O-linked glycoproteins	519:550	This procedure can be modified and applied to a variety of N- and/or O-linked glycoproteins.
33377107	4	28	gly	glycoproteins	538:550	arg1	glycoproteins					538:550	N- and/or O-linked glycoproteins	519:550	N- and/or O-linked glycoproteins	519:550	This procedure can be modified and applied to a variety of N- and/or O-linked glycoproteins.
33377107	1	29	gly	glycosylation	195:207	arg1	protein					229:235	SARS-CoV-2 spike protein	212:235	SARS-CoV-2 spike protein	212:235	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	5	30	theme	certain	687:693	arg1	glycoproteins					695:707	certain glycoproteins	687:707	certain glycoproteins alone	687:713	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	3	31	theme	structural	386:395	arg1	characterization					397:412	structural characterization	386:412	structural characterization on any glycan assignments by glycoproteomics	386:457	Glycomics provides structural characterization on any glycan assignments by glycoproteomics.
33377107	4	32	theme	O-linked	529:536	arg1	glycoproteins					538:550	N- and/or O-linked glycoproteins	519:550	N- and/or O-linked glycoproteins	519:550	This procedure can be modified and applied to a variety of N- and/or O-linked glycoproteins.
33377107	2	33	theme	site-specific	316:328	arg1	microheterogeneity					330:347	site-specific microheterogeneity	316:347	site-specific microheterogeneity of glycoproteins	316:364	Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins.
33377107	6	34	dep	use	776:778	arg1	the					772:774	the	772:774	the	772:774	For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).
33377107	1	35	theme	site-specific	165:177	arg1	N-					179:180	site-specific N-	165:180	site-specific N-	165:180	This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry.
33377107	5	36	dep	one	735:737	arg1	another					739:745	another	739:745	another	739:745	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
33377107	3	37	from	characterization	397:412	arg1	assignments					428:438	any glycan assignments	417:438	any glycan assignments	417:438	Glycomics provides structural characterization on any glycan assignments by glycoproteomics.
33377107	0	38	theme	spike	89:93	arg1	protein					95:101	SARS-CoV-2 spike protein	78:101	SARS-CoV-2 spike protein	78:101	Glycomics-informed glycoproteomic analysis of site-specific glycosylation for SARS-CoV-2 spike protein.
33377107	6	39	from	details	761:767	arg1	use					776:778	use	776:778	use	776:778	For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).
33377107	6	39	from	details	761:767	arg1	execution					784:792	execution	784:792	execution	784:792	For complete details on the use and execution of this protocol, please refer to Zhao et al. (2020).
33377107	5	40	theme	3D	650:651	arg1	simulations					672:682	3D molecular dynamics simulations	650:682	3D molecular dynamics simulations of certain glycoproteins alone	650:713	Combined with bioinformatics, the glycomics-informed glycoproteomics may be useful in generating 3D molecular dynamics simulations of certain glycoproteins alone or interacting with one another.
32326134	0	0	theme	O-Glycosylation	95:109	arg1	Sites					111:115	O-Glycosylation Sites	95:115	O-Glycosylation Sites in Bovine Submaxillary Mucin	95:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	4	1	theme	GlcNAc	1118:1123	arg1	GalNAc					1125:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	1	theme	GlcNAc	1118:1123	arg1	types					1056:1060	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	2	theme	BSM	705:707	arg1	μg					699:700	1 μg	697:700	1 μg of BSM	697:707	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	728TMTTRTSVVV					1300:1312	728TMTTRTSVVV	1300:1312	728TMTTRTSVVV	1300:1312	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	56SGETRTSVI					1231:1241	56SGETRTSVI	1231:1241	56SGETRTSVI	1231:1241	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	1080RPEDNTAVA					1319:1331	1080RPEDNTAVA	1319:1331	1080RPEDNTAVA	1319:1331	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	307RPSYGAL					1277:1286	307RPSYGAL	1277:1286	307RPSYGAL	1277:1286	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	625QTLGPL					1289:1297	625QTLGPL	1289:1297	625QTLGPL	1289:1297	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	O-glycopeptides					1197:1211	O-glycopeptides	1197:1211	O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM	1197:1362	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	bold					1214:1217	bold	1214:1217	bold underlined	1214:1228	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	259SHSSSGRSRTI					1244:1257	259SHSSSGRSRTI	1244:1257	259SHSSSGRSRTI	1244:1257	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	3	gly	O-glycopeptides	1197:1211	arg2	272GSPSSVSSAEQI					1260:1274	272GSPSSVSSAEQI	1260:1274	272GSPSSVSSAEQI	1260:1274	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	6	4	theme	mucin-type	1541:1550	arg1	O-glycans					1552:1560	mucin-type O-glycans	1541:1560	mucin-type O-glycans	1541:1560	The gel-forming mucins share common domain structures and glycosylation patterns; these results could provide useful information on mucin-type O-glycans.
32326134	1	5	link	Ser/Thr-linked	222:235	arg1	O-glycans					246:254	O-glycans	246:254	O-glycans	246:254	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	5	link	Ser/Thr-linked	222:235	arg1	glycans					237:243	Ser/Thr-linked glycans	222:243	Ser/Thr-linked glycans (O-glycans)	222:255	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	4	6	theme	core	1041:1044	arg1	[Gal-GalNAc					1062:1072	[Gal-GalNAc	1062:1072	[Gal-GalNAc	1062:1072	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	6	theme	core	1041:1044	arg1	GalNAc					1125:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	6	theme	core	1041:1044	arg1	GlcNAc-GalNAc					1095:1107	GlcNAc-GalNAc	1095:1107	GlcNAc-GalNAc	1095:1107	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	6	theme	core	1041:1044	arg1	GalNAc-GalNAc					1137:1149	GalNAc-GalNAc	1137:1149	GalNAc-GalNAc	1137:1149	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	6	theme	core	1041:1044	arg1	types					1056:1060	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	6	theme	core	1041:1044	arg1	GalNAc					1087:1092	Gal-(GlcNAc)GalNAc	1075:1092	Gal-(GlcNAc)GalNAc	1075:1092	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	7	dep	constituents	846:857	arg1	sialylation					860:870	sialylation	860:870	sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan)	860:935	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	6	8	from	information	1526:1536	arg1	O-glycans					1552:1560	mucin-type O-glycans	1541:1560	mucin-type O-glycans	1541:1560	The gel-forming mucins share common domain structures and glycosylation patterns; these results could provide useful information on mucin-type O-glycans.
32326134	1	9	gly	glycoprotein	196:207	arg1	glycoprotein					196:207	a gel-forming glycoprotein polymer	182:215	a gel-forming glycoprotein polymer	182:215	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	7	10	theme	first	1575:1579	arg1	study					1581:1585	the first study	1571:1585	the first study to characterize O-glycans and identify O-glycosylation sites in BSM	1571:1653	This is the first study to characterize O-glycans and identify O-glycosylation sites in BSM.
32326134	7	10	theme	first	1575:1579	arg1	This					1563:1566	This	1563:1566	This	1563:1566	This is the first study to characterize O-glycans and identify O-glycosylation sites in BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	259SHSSSGRSRTI					1244:1257	259SHSSSGRSRTI	1244:1257	259SHSSSGRSRTI	1244:1257	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	bold					1214:1217	bold	1214:1217	bold underlined	1214:1228	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	272GSPSSVSSAEQI					1260:1274	272GSPSSVSSAEQI	1260:1274	272GSPSSVSSAEQI	1260:1274	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	728TMTTRTSVVV					1300:1312	728TMTTRTSVVV	1300:1312	728TMTTRTSVVV	1300:1312	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	1080RPEDNTAVA					1319:1331	1080RPEDNTAVA	1319:1331	1080RPEDNTAVA	1319:1331	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	56SGETRTSVI					1231:1241	56SGETRTSVI	1231:1241	56SGETRTSVI	1231:1241	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	307RPSYGAL					1277:1286	307RPSYGAL	1277:1286	307RPSYGAL	1277:1286	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	625QTLGPL					1289:1297	625QTLGPL	1289:1297	625QTLGPL	1289:1297	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	11	dep	O-glycopeptides	1197:1211	arg1	O-glycopeptides					1197:1211	O-glycopeptides	1197:1211	O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM	1197:1362	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	0	12	theme	Sites	111:115	arg1	Characterization					28:43	Structural and Quantitative Characterization	0:43	Structural and Quantitative Characterization of Mucin-Type O-Glycans	0:67	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	0	12	theme	Sites	111:115	arg1	Identification					77:90	the Identification	73:90	the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin	73:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	6	13	theme	useful	1519:1524	arg1	information					1526:1536	useful information	1519:1536	useful information on mucin-type O-glycans	1519:1560	The gel-forming mucins share common domain structures and glycosylation patterns; these results could provide useful information on mucin-type O-glycans.
32326134	6	14	theme	gel-forming	1413:1423	arg1	mucins					1425:1430	The gel-forming mucins	1409:1430	The gel-forming mucins	1409:1430	The gel-forming mucins share common domain structures and glycosylation patterns; these results could provide useful information on mucin-type O-glycans.
32326134	3	15	theme	liquid	522:527	arg1	spectrometry					556:567	liquid chromatography-tandem mass spectrometry	522:567	liquid chromatography-tandem mass spectrometry	522:567	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	0	16	theme	Submaxillary	127:138	arg1	Mucin					140:144	Bovine Submaxillary Mucin	120:144	Bovine Submaxillary Mucin	120:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	4	17	theme	structure	1046:1054	arg1	[Gal-GalNAc					1062:1072	[Gal-GalNAc	1062:1072	[Gal-GalNAc	1062:1072	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	17	theme	structure	1046:1054	arg1	GalNAc					1125:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	17	theme	structure	1046:1054	arg1	GlcNAc-GalNAc					1095:1107	GlcNAc-GalNAc	1095:1107	GlcNAc-GalNAc	1095:1107	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	17	theme	structure	1046:1054	arg1	GalNAc-GalNAc					1137:1149	GalNAc-GalNAc	1137:1149	GalNAc-GalNAc	1137:1149	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	17	theme	structure	1046:1054	arg1	types					1056:1060	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	17	theme	structure	1046:1054	arg1	GalNAc					1087:1092	Gal-(GlcNAc)GalNAc	1075:1092	Gal-(GlcNAc)GalNAc	1075:1092	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	0	18	theme	Bovine	120:125	arg1	Mucin					140:144	Bovine Submaxillary Mucin	120:144	Bovine Submaxillary Mucin	120:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	3	19	theme	quantitative	430:441	arg1	characteristics					443:457	the structural and quantitative characteristics	411:457	the structural and quantitative characteristics of O-glycans	411:470	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	4	20	theme	quantities	910:919	arg1	sum					894:896	sum	894:896	sum of relative quantities of each glycan	894:934	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	21	theme	GlcNAc-	1110:1116	arg1	GalNAc					1125:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	21	theme	GlcNAc-	1110:1116	arg1	types					1056:1060	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	6	22	theme	common	1438:1443	arg1	structures					1452:1461	common domain structures	1438:1461	common domain structures	1438:1461	The gel-forming mucins share common domain structures and glycosylation patterns; these results could provide useful information on mucin-type O-glycans.
32326134	1	23	theme	gel-forming	184:194	arg1	mucin					167:171	Bovine submaxillary mucin	147:171	Bovine submaxillary mucin (BSM)	147:177	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	23	theme	gel-forming	184:194	arg1	polymer					209:215	a gel-forming glycoprotein polymer	182:215	a gel-forming glycoprotein polymer	182:215	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	0	24	theme	Structural	0:9	arg1	Characterization					28:43	Structural and Quantitative Characterization	0:43	Structural and Quantitative Characterization of Mucin-Type O-Glycans	0:67	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	7	25	gly	O-glycosylation	1626:1640	arg2	sites					1642:1646	O-glycosylation sites	1626:1646	O-glycosylation sites in BSM	1626:1653	This is the first study to characterize O-glycans and identify O-glycosylation sites in BSM.
32326134	4	26	theme	Gal-	1075:1078	arg1	GalNAc					1087:1092	Gal-(GlcNAc)GalNAc	1075:1092	Gal-(GlcNAc)GalNAc	1075:1092	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	26	theme	Gal-	1075:1078	arg1	types					1056:1060	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	1	27	theme	glycoprotein	196:207	arg1	mucin					167:171	Bovine submaxillary mucin	147:171	Bovine submaxillary mucin (BSM)	147:177	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	27	theme	glycoprotein	196:207	arg1	polymer					209:215	a gel-forming glycoprotein polymer	182:215	a gel-forming glycoprotein polymer	182:215	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	4	28	theme	glycan	929:934	arg1	sum					894:896	sum	894:896	sum of relative quantities of each glycan	894:934	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	5	29	gly	O-glycosylation	1153:1167	arg2	sites					1169:1173	O-glycosylation sites	1153:1173	O-glycosylation sites	1153:1173	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	4	30	dep	O-glycans	667:675	arg1	%					681:681	100%	678:681	100%	678:681	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	7	31	from	sites	1642:1646	arg1	BSM					1651:1653	BSM	1651:1653	BSM	1651:1653	This is the first study to characterize O-glycans and identify O-glycosylation sites in BSM.
32326134	0	32	theme	Quantitative	15:26	arg1	Characterization					28:43	Structural and Quantitative Characterization	0:43	Structural and Quantitative Characterization of Mucin-Type O-Glycans	0:67	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	0	33	theme	Mucin-Type	48:57	arg1	O-Glycans					59:67	Mucin-Type O-Glycans	48:67	Mucin-Type O-Glycans	48:67	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	3	34	theme	mass	551:554	arg1	spectrometry					556:567	liquid chromatography-tandem mass spectrometry	522:567	liquid chromatography-tandem mass spectrometry	522:567	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	4	35	dep	sialylation	860:870	arg1	O-glycans					876:884	14 O-glycans	873:884	14 O-glycans	873:884	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	35	dep	sialylation	860:870	arg1	%					989:989	20; 17.5%	981:989	20; 17.5%	981:989	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	35	dep	sialylation	860:870	arg1	non-sialylation					938:952	non-sialylation	938:952	non-sialylation (20; 18.1%)	938:964	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	35	dep	sialylation	860:870	arg1	fucosylation					967:978	fucosylation	967:978	fucosylation (20; 17.5%)	967:990	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	35	dep	sialylation	860:870	arg1	%					1029:1029	6; 3.6%	1023:1029	6; 3.6%	1023:1029	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	35	dep	sialylation	860:870	arg1	terminal-galactosylation					997:1020	terminal-galactosylation	997:1020	terminal-galactosylation	997:1020	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	35	dep	sialylation	860:870	arg1	%					963:963	20; 18.1%	955:963	20; 18.1%	955:963	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	36	theme	GlcNAc	1080:1085	arg1	GalNAc					1087:1092	Gal-(GlcNAc)GalNAc	1075:1092	Gal-(GlcNAc)GalNAc	1075:1092	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	36	theme	GlcNAc	1080:1085	arg1	types					1056:1060	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	37	dep	%	681:681	arg1	pmol					688:691	1.1 pmol	684:691	1.1 pmol per 1 μg of BSM	684:707	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	3	38	theme	O-glycans	462:470	arg1	characteristics					443:457	the structural and quantitative characteristics	411:457	the structural and quantitative characteristics of O-glycans	411:470	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	3	39	theme	O-glycosylation	487:501	arg1	sites					503:507	O-glycosylation sites	487:507	O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry	487:567	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	5	40	theme	proteolytic	1348:1358	arg1	BSM					1360:1362	proteolytic BSM	1348:1362	proteolytic BSM	1348:1362	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	0	41	from	Identification	77:90	arg1	Mucin					140:144	Bovine Submaxillary Mucin	120:144	Bovine Submaxillary Mucin	120:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	5	42	theme	O-glycosylation	1153:1167	arg1	sites					1169:1173	O-glycosylation sites	1153:1173	O-glycosylation sites	1153:1173	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	1	43	theme	Ser/Thr-linked	222:235	arg1	O-glycans					246:254	O-glycans	246:254	O-glycans	246:254	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	43	theme	Ser/Thr-linked	222:235	arg1	glycans					237:243	Ser/Thr-linked glycans	222:243	Ser/Thr-linked glycans (O-glycans)	222:255	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	3	44	theme	structural	415:424	arg1	characteristics					443:457	the structural and quantitative characteristics	411:457	the structural and quantitative characteristics of O-glycans	411:470	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	6	45	theme	glycosylation	1467:1479	arg1	patterns					1481:1488	glycosylation patterns	1467:1488	glycosylation patterns	1467:1488	The gel-forming mucins share common domain structures and glycosylation patterns; these results could provide useful information on mucin-type O-glycans.
32326134	5	46	theme	BSM	1404:1406	arg1	BSM					1404:1406	BSM	1404:1406	BSM	1404:1406	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	5	46	theme	BSM	1404:1406	arg1	domains					1393:1399	the four domains	1384:1399	the four domains of BSM	1384:1406	O-glycosylation sites were identified using O-glycopeptides (bold underlined; 56SGETRTSVI, 259SHSSSGRSRTI, 272GSPSSVSSAEQI, 307RPSYGAL, 625QTLGPL, 728TMTTRTSVVV, and 1080RPEDNTAVA) obtained from proteolytic BSM; these sites are in the four domains of BSM.
32326134	3	47	from	sites	503:507	arg1	BSM					512:514	BSM	512:514	BSM using liquid chromatography-tandem mass spectrometry	512:567	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	3	48	theme	chromatography-tandem	529:549	arg1	spectrometry					556:567	liquid chromatography-tandem mass spectrometry	522:567	liquid chromatography-tandem mass spectrometry	522:567	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	0	49	theme	O-Glycans	59:67	arg1	Characterization					28:43	Structural and Quantitative Characterization	0:43	Structural and Quantitative Characterization of Mucin-Type O-Glycans	0:67	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	0	49	theme	O-Glycans	59:67	arg1	Identification					77:90	the Identification	73:90	the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin	73:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	3	50	gly	O-glycosylation	487:501	arg2	sites					503:507	O-glycosylation sites	487:507	O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry	487:567	This study investigates the structural and quantitative characteristics of O-glycans and identifies O-glycosylation sites in BSM using liquid chromatography-tandem mass spectrometry.
32326134	2	51	theme	O-glycosylation	347:361	arg1	details					336:342	details	336:342	details of O-glycosylation	336:361	However, details of O-glycosylation have not been reported.
32326134	1	52	theme	Bovine	147:152	arg1	BSM					174:176	BSM	174:176	BSM	174:176	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	52	theme	Bovine	147:152	arg1	polymer					209:215	a gel-forming glycoprotein polymer	182:215	a gel-forming glycoprotein polymer	182:215	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	52	theme	Bovine	147:152	arg1	mucin					167:171	Bovine submaxillary mucin	147:171	Bovine submaxillary mucin (BSM)	147:177	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	4	53	theme	relative	649:656	arg1	%					646:646	%	646:646	%	646:646	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	53	theme	relative	649:656	arg1	quantities					634:643	their quantities	628:643	their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM)	628:708	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	54	dep	O-glycans	876:884	arg1	sum					894:896	sum	894:896	sum of relative quantities of each glycan	894:934	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	54	dep	O-glycans	876:884	arg1	%					891:891	81.9%	887:891	81.9%	887:891	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	6	55	theme	domain	1445:1450	arg1	structures					1452:1461	common domain structures	1438:1461	common domain structures	1438:1461	The gel-forming mucins share common domain structures and glycosylation patterns; these results could provide useful information on mucin-type O-glycans.
32326134	1	56	theme	submaxillary	154:165	arg1	BSM					174:176	BSM	174:176	BSM	174:176	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	56	theme	submaxillary	154:165	arg1	polymer					209:215	a gel-forming glycoprotein polymer	182:215	a gel-forming glycoprotein polymer	182:215	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	1	56	theme	submaxillary	154:165	arg1	mucin					167:171	Bovine submaxillary mucin	147:171	Bovine submaxillary mucin (BSM)	147:177	Bovine submaxillary mucin (BSM) is a gel-forming glycoprotein polymer, and Ser/Thr-linked glycans (O-glycans) are important in regulating BSM's viscoelasticity and polymerization.
32326134	4	57	dep	major	734:738	arg1	O-glycans					795:803	O-glycans	795:803	O-glycans	795:803	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	0	58	from	Sites	111:115	arg1	Mucin					140:144	Bovine Submaxillary Mucin	120:144	Bovine Submaxillary Mucin	120:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	4	59	theme	%	762:762	arg1	%					767:767	0.1%-1.0%	759:767	0.1%-1.0%	759:767	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	59	theme	%	762:762	arg1	minor					752:756	minor	752:756	minor	752:756	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	7	60	theme	O-glycosylation	1626:1640	arg1	sites					1642:1646	O-glycosylation sites	1626:1646	O-glycosylation sites in BSM	1626:1653	This is the first study to characterize O-glycans and identify O-glycosylation sites in BSM.
32326134	4	61	theme	total	661:665	arg1	O-glycans					667:675	total O-glycans	661:675	total O-glycans (100%; 1.1 pmol per 1 μg of BSM)	661:708	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	62	theme	relative	901:908	arg1	quantities					910:919	relative quantities	901:919	relative quantities	901:919	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	0	63	from	Characterization	28:43	arg1	Mucin					140:144	Bovine Submaxillary Mucin	120:144	Bovine Submaxillary Mucin	120:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	4	64	dep	types	1056:1060	arg1	[Gal-GalNAc					1062:1072	[Gal-GalNAc	1062:1072	[Gal-GalNAc	1062:1072	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	64	dep	types	1056:1060	arg1	GalNAc					1125:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	GlcNAc-(GlcNAc)GalNAc	1110:1130	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	64	dep	types	1056:1060	arg1	GlcNAc-GalNAc					1095:1107	GlcNAc-GalNAc	1095:1107	GlcNAc-GalNAc	1095:1107	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	64	dep	types	1056:1060	arg1	GalNAc-GalNAc					1137:1149	GalNAc-GalNAc	1137:1149	GalNAc-GalNAc	1137:1149	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	64	dep	types	1056:1060	arg1	types					1056:1060	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc]	1037:1150	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	4	64	dep	types	1056:1060	arg1	GalNAc					1087:1092	Gal-(GlcNAc)GalNAc	1075:1092	Gal-(GlcNAc)GalNAc	1075:1092	The O-glycans (consisting of di- to octa-saccharides) and their quantities (%) relative to total O-glycans (100%; 1.1 pmol per 1 μg of BSM) were identified with 14 major (>1.0%), 12 minor (0.1%-1.0%), and eight trace (<0.1%) O-glycans, which were characterized based on their constituents (sialylation (14 O-glycans; 81.9%, sum of relative quantities of each glycan), non-sialylation (20; 18.1%), fucosylation (20; 17.5%), and terminal-galactosylation (6; 3.6%)) and six core structure types [Gal-GalNAc, Gal-(GlcNAc)GalNAc, GlcNAc-GalNAc, GlcNAc-(GlcNAc)GalNAc, and GalNAc-GalNAc].
32326134	0	65	from	Mucin	140:144	arg1	Characterization					28:43	Structural and Quantitative Characterization	0:43	Structural and Quantitative Characterization of Mucin-Type O-Glycans	0:67	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
32326134	0	65	from	Mucin	140:144	arg1	Identification					77:90	the Identification	73:90	the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin	73:144	Structural and Quantitative Characterization of Mucin-Type O-Glycans and the Identification of O-Glycosylation Sites in Bovine Submaxillary Mucin.
34962767	12	0	theme	structures	1912:1921	arg1	range					1886:1890	the range	1882:1890	the range of complex O-glycan structures	1882:1921	In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.
34962767	12	0	theme	structures	1912:1921	arg1	identification					1847:1860	the identification	1843:1860	the identification of O-glycosites	1843:1876	In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.
34962767	10	1	gly	asialylated	1512:1522	arg1	O-glycans					1524:1532	sialylated and asialylated O-glycans	1497:1532	sialylated and asialylated O-glycans of varying complexity	1497:1554	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	11	2	theme	phosphatase	1746:1756	arg1	C					1758:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	2	theme	phosphatase	1746:1756	arg1	glycoproteins					1659:1671	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C	1646:1758	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1646:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	1	3	gly	glycoproteins	210:222	arg1	glycoproteins					210:222	glycoproteins	210:222	glycoproteins	210:222	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	8	4	gly	O-glycosites	1239:1250	arg2	O-glycosites					1239:1250	two adjacent O-glycosites	1226:1250	two adjacent O-glycosites	1226:1250	The enzyme does not cleave between two adjacent O-glycosites, indicating that O-glycosylated serine/threonine is not allowed at position P1.
34962767	1	5	theme	effective	278:286	arg1	tools					298:302	effective enzymatic tools	278:302	effective enzymatic tools that enable their analysis	278:329	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	10	6	gly	sialylated	1497:1506	arg1	O-glycans					1524:1532	sialylated and asialylated O-glycans	1497:1532	sialylated and asialylated O-glycans of varying complexity	1497:1554	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	3	7	gly	glycoproteins	711:723	arg1	glycoproteins					711:723	glycoproteins	711:723	glycoproteins	711:723	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	11	8	theme	glycopeptide	1781:1792	arg1	enrichment					1794:1803	glycopeptide enrichment	1781:1803	glycopeptide enrichment	1781:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	7	9	theme	aspartic	1176:1183	arg1	acid					1185:1188	aspartic acid	1176:1188	aspartic acid	1176:1188	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	3	10	theme	inefficient	605:615	arg1	cleavage					617:624	inefficient cleavage	605:624	inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias	605:749	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	1	11	theme	tools	298:302	arg1	lack					270:273	a lack	268:273	a lack of effective enzymatic tools that enable their analysis	268:329	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	8	12	theme	adjacent	1230:1237	arg1	O-glycosites					1239:1250	two adjacent O-glycosites	1226:1250	two adjacent O-glycosites	1226:1250	The enzyme does not cleave between two adjacent O-glycosites, indicating that O-glycosylated serine/threonine is not allowed at position P1.
34962767	11	13	dep	glycoproteins	1659:1671	arg1	C					1758:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	13	dep	glycoproteins	1659:1671	arg1	factor					1704:1709	granulocyte colony-stimulating factor	1673:1709	granulocyte colony-stimulating factor	1673:1709	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	13	dep	glycoproteins	1659:1671	arg1	glycoproteins					1659:1671	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C	1646:1758	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1646:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	8	14	gly	O-glycosylated	1269:1282	arg1	serine/threonine					1284:1299	O-glycosylated serine/threonine	1269:1299	O-glycosylated serine/threonine	1269:1299	The enzyme does not cleave between two adjacent O-glycosites, indicating that O-glycosylated serine/threonine is not allowed at position P1.
34962767	6	15	from	selectivity	938:948	arg1	activity					973:980	IMPa activity	968:980	IMPa activity	968:980	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	7	16	theme	P1	1156:1157	arg1	position					1159:1166	the P1 position	1152:1166	the P1 position	1152:1166	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	11	17	theme	O-glycoproteomic	1598:1613	arg1	workflow					1615:1622	a one-step O-glycoproteomic workflow	1587:1622	a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1587:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	4	18	theme	analytical	778:787	arg1	application					789:799	their analytical application	772:799	their analytical application	772:799	These factors limit their analytical application.
34962767	7	19	theme	amino	1137:1141	arg1	acids					1143:1147	most amino acids	1132:1147	most amino acids at the P1 position	1132:1166	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	3	20	theme	high	673:676	arg1	selectivity					678:688	high selectivity	673:688	high selectivity for certain types of glycoproteins	673:723	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	7	21	theme	P1	1093:1094	arg1	preference					1104:1113	no specific P1 residue preference	1081:1113	no specific P1 residue preference	1081:1113	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	6	22	theme	peptides	1028:1035	arg1	array					1009:1013	an array	1006:1013	an array of synthetic peptides and their glycoforms	1006:1056	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	12	23	gly	O-glycosites	1865:1876	arg2	O-glycosites					1865:1876	O-glycosites	1865:1876	O-glycosites	1865:1876	In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.
34962767	5	24	from	aeruginosa	909:918	arg1	capabilities					833:844	the capabilities	829:844	the capabilities of an immunomodulating metalloprotease (IMPa) from Pseudomonas aeruginosa	829:918	In this study, we examined the capabilities of an immunomodulating metalloprotease (IMPa) from Pseudomonas aeruginosa.
34962767	1	25	theme	O-glycans	170:178	arg1	Characterization					139:154	Characterization	139:154	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins	139:222	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	0	26	theme	Glycoproteins	70:82	arg1	Analysis					58:65	Improved Analysis	49:65	Improved Analysis of Glycoproteins and Glycopeptides	49:100	A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides Containing Intact Complex O-Glycans.
34962767	10	27	theme	asialylated	1512:1522	arg1	O-glycans					1524:1532	sialylated and asialylated O-glycans	1497:1532	sialylated and asialylated O-glycans of varying complexity	1497:1554	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	0	28	theme	Glycopeptides	88:100	arg1	Analysis					58:65	Improved Analysis	49:65	Improved Analysis of Glycoproteins and Glycopeptides	49:100	A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides Containing Intact Complex O-Glycans.
34962767	10	29	theme	sialylated	1497:1506	arg1	O-glycans					1524:1532	sialylated and asialylated O-glycans	1497:1532	sialylated and asialylated O-glycans of varying complexity	1497:1554	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	0	30	theme	Intact	113:118	arg1	O-Glycans					128:136	Intact Complex O-Glycans	113:136	Intact Complex O-Glycans	113:136	A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides Containing Intact Complex O-Glycans.
34962767	10	31	theme	complexity	1545:1554	arg1	O-glycans					1524:1532	sialylated and asialylated O-glycans	1497:1532	sialylated and asialylated O-glycans of varying complexity	1497:1554	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	9	32	with	Glycopeptides	1332:1344	arg1	acids					1371:1375	as few as two amino acids	1351:1375	as few as two amino acids	1351:1375	Glycopeptides with as few as two amino acids on either side of an O-glycosite were cleaved by IMPa.
34962767	9	33	theme	O-glycosite	1398:1408	arg1	side					1387:1390	either side	1380:1390	either side of an O-glycosite	1380:1408	Glycopeptides with as few as two amino acids on either side of an O-glycosite were cleaved by IMPa.
34962767	5	34	theme	immunomodulating	852:867	arg1	metalloprotease					869:883	an immunomodulating metalloprotease	849:883	an immunomodulating metalloprotease (IMPa)	849:890	In this study, we examined the capabilities of an immunomodulating metalloprotease (IMPa) from Pseudomonas aeruginosa.
34962767	5	34	theme	immunomodulating	852:867	arg1	IMPa					886:889	IMPa	886:889	IMPa	886:889	In this study, we examined the capabilities of an immunomodulating metalloprotease (IMPa) from Pseudomonas aeruginosa.
34962767	3	35	theme	glycoproteins	711:723	arg1	types					702:706	certain types	694:706	certain types of glycoproteins	694:723	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	11	36	theme	colony-stimulating	1685:1702	arg1	glycoproteins					1659:1671	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C	1646:1758	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1646:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	36	theme	colony-stimulating	1685:1702	arg1	factor					1704:1709	granulocyte colony-stimulating factor	1673:1709	granulocyte colony-stimulating factor	1673:1709	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	6	37	theme	sequence	929:936	arg1	selectivity					938:948	Peptide sequence selectivity	921:948	Peptide sequence selectivity	921:948	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	11	38	theme	glycoproteins	1659:1671	arg1	glycoprofiling					1628:1641	glycoprofiling	1628:1641	glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1628:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	10	39	contain	carrying	1488:1495	arg1	peptides					1466:1473	peptides	1466:1473	peptides	1466:1473	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	10	39	contain	carrying	1488:1495	arg2	O-glycans					1524:1532	sialylated and asialylated O-glycans	1497:1532	sialylated and asialylated O-glycans of varying complexity	1497:1554	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	12	40	theme	O-glycan	1903:1910	arg1	structures					1912:1921	complex O-glycan structures	1895:1921	complex O-glycan structures	1895:1921	In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.
34962767	3	41	theme	sequence	737:744	arg1	bias					746:749	protein sequence bias	729:749	protein sequence bias	729:749	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	11	42	theme	tyrosine-protein	1729:1744	arg1	phosphatase					1746:1756	receptor-type tyrosine-protein phosphatase	1715:1756	receptor-type tyrosine-protein phosphatase C	1715:1758	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	3	43	theme	specificity	572:582	arg1	cleavage					617:624	inefficient cleavage	605:624	inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias	605:749	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	3	43	theme	specificity	572:582	arg1	constraints					584:594	specificity constraints	572:594	specificity constraints	572:594	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	5	44	theme	metalloprotease	869:883	arg1	capabilities					833:844	the capabilities	829:844	the capabilities of an immunomodulating metalloprotease (IMPa) from Pseudomonas aeruginosa	829:918	In this study, we examined the capabilities of an immunomodulating metalloprotease (IMPa) from Pseudomonas aeruginosa.
34962767	7	45	contain	has	1077:1079	arg1	IMPa					1072:1075	IMPa	1072:1075	IMPa	1072:1075	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	7	45	contain	has	1077:1079	arg2	preference					1104:1113	no specific P1 residue preference	1081:1113	no specific P1 residue preference	1081:1113	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	9	46	from	Glycopeptides	1332:1344	arg1	side					1387:1390	either side	1380:1390	either side of an O-glycosite	1380:1408	Glycopeptides with as few as two amino acids on either side of an O-glycosite were cleaved by IMPa.
34962767	1	47	theme	enzymatic	288:296	arg1	tools					298:302	effective enzymatic tools	278:302	effective enzymatic tools that enable their analysis	278:329	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	3	48	theme	glycoproteins	629:641	arg1	cleavage					617:624	inefficient cleavage	605:624	inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias	605:749	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	1	49	attach	linked	180:185	arg1	serine/threonine					190:205	serine/threonine	190:205	serine/threonine of glycoproteins	190:222	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	1	49	attach	linked	180:185	arg2	O-glycans					170:178	mucin-type O-glycans	159:178	mucin-type O-glycans linked to serine/threonine of glycoproteins	159:222	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	11	50	theme	one-step	1589:1596	arg1	workflow					1615:1622	a one-step O-glycoproteomic workflow	1587:1622	a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1587:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	1	51	theme	glycoproteins	210:222	arg1	serine/threonine					190:205	serine/threonine	190:205	serine/threonine of glycoproteins	190:222	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	6	52	theme	IMPa	968:971	arg1	activity					973:980	IMPa activity	968:980	IMPa activity	968:980	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	11	53	gly	glycopeptide	1781:1792	arg2	glycopeptide					1781:1792	glycopeptide enrichment	1781:1803	glycopeptide enrichment	1781:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	2	54	theme	several	342:348	arg1	endoproteases					368:380	several O-glycan-specific endoproteases	342:380	several O-glycan-specific endoproteases that can cleave the protein adjacent to the appended glycan	342:440	Recently, several O-glycan-specific endoproteases that can cleave the protein adjacent to the appended glycan have been described.
34962767	12	55	theme	O-glycosites	1865:1876	arg1	range					1886:1890	the range	1882:1890	the range of complex O-glycan structures	1882:1921	In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.
34962767	12	55	theme	O-glycosites	1865:1876	arg1	identification					1847:1860	the identification	1843:1860	the identification of O-glycosites	1843:1876	In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.
34962767	8	56	theme	position	1319:1326	arg1	P1					1328:1329	position P1	1319:1329	position P1	1319:1329	The enzyme does not cleave between two adjacent O-glycosites, indicating that O-glycosylated serine/threonine is not allowed at position P1.
34962767	6	57	from	impact	958:963	arg1	activity					973:980	IMPa activity	968:980	IMPa activity	968:980	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	6	58	theme	glycoforms	1047:1056	arg1	array					1009:1013	an array	1006:1013	an array of synthetic peptides and their glycoforms	1006:1056	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	7	59	theme	most	1132:1135	arg1	acids					1143:1147	most amino acids	1132:1147	most amino acids at the P1 position	1132:1166	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	8	60	theme	O-glycosylated	1269:1282	arg1	serine/threonine					1284:1299	O-glycosylated serine/threonine	1269:1299	O-glycosylated serine/threonine	1269:1299	The enzyme does not cleave between two adjacent O-glycosites, indicating that O-glycosylated serine/threonine is not allowed at position P1.
34962767	3	61	gly	sialylated	651:660	arg1	O-glycans					662:670	sialylated O-glycans	651:670	sialylated O-glycans	651:670	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	3	62	theme	sialylated	651:660	arg1	O-glycans					662:670	sialylated O-glycans	651:670	sialylated O-glycans	651:670	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	7	63	theme	residue	1096:1102	arg1	preference					1104:1113	no specific P1 residue preference	1081:1113	no specific P1 residue preference	1081:1113	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	6	64	theme	synthetic	1018:1026	arg1	peptides					1028:1035	synthetic peptides	1018:1035	synthetic peptides	1018:1035	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	3	65	gly	glycoproteins	629:641	arg1	glycoproteins					629:641	glycoproteins	629:641	glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias	629:749	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	3	66	theme	certain	694:700	arg1	types					702:706	certain types	694:706	certain types of glycoproteins	694:723	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	7	67	theme	specific	1084:1091	arg1	preference					1104:1113	no specific P1 residue preference	1081:1113	no specific P1 residue preference	1081:1113	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	1	68	theme	mucin-type	159:168	arg1	O-glycans					170:178	mucin-type O-glycans	159:178	mucin-type O-glycans linked to serine/threonine of glycoproteins	159:222	Characterization of mucin-type O-glycans linked to serine/threonine of glycoproteins is technically challenging, in part, due to a lack of effective enzymatic tools that enable their analysis.
34962767	3	69	contain	have	567:570	arg2	constraints					584:594	specificity constraints	572:594	specificity constraints	572:594	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	3	69	contain	have	567:570	arg2	cleavage					617:624	inefficient cleavage	605:624	inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias	605:749	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	3	69	contain	have	567:570	arg1	O-glycoproteases					550:565	known O-glycoproteases	544:565	known O-glycoproteases	544:565	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	11	70	theme	IMPa	1579:1582	arg1	use					1572:1574	the use	1568:1574	the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1568:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	0	71	theme	Complex	120:126	arg1	O-Glycans					128:136	Intact Complex O-Glycans	113:136	Intact Complex O-Glycans	113:136	A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides Containing Intact Complex O-Glycans.
34962767	9	72	theme	amino	1365:1369	arg1	acids					1371:1375	as few as two amino acids	1351:1375	as few as two amino acids	1351:1375	Glycopeptides with as few as two amino acids on either side of an O-glycosite were cleaved by IMPa.
34962767	11	73	from	use	1572:1574	arg1	workflow					1615:1622	a one-step O-glycoproteomic workflow	1587:1622	a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1587:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	3	74	theme	enzymes	535:541	arg1	biochemistry					513:524	the biochemistry	509:524	the biochemistry of these enzymes	509:541	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	10	75	theme	varying	1537:1543	arg1	complexity					1545:1554	varying complexity	1537:1554	varying complexity	1537:1554	Finally, IMPa efficiently cleaved peptides and proteins carrying sialylated and asialylated O-glycans of varying complexity.
34962767	9	76	gly	O-glycosite	1398:1408	arg2	O-glycosite					1398:1408	an O-glycosite	1395:1408	an O-glycosite	1395:1408	Glycopeptides with as few as two amino acids on either side of an O-glycosite were cleaved by IMPa.
34962767	2	77	theme	appended	426:433	arg1	glycan					435:440	the appended glycan	422:440	the appended glycan	422:440	Recently, several O-glycan-specific endoproteases that can cleave the protein adjacent to the appended glycan have been described.
34962767	0	78	theme	Broad-Specificity	2:18	arg1	O-Glycoprotease					20:34	A Broad-Specificity O-Glycoprotease	0:34	A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides	0:100	A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides Containing Intact Complex O-Glycans.
34962767	3	79	theme	significant	471:481	arg1	progress					483:490	significant progress	471:490	significant progress in understanding the biochemistry of these enzymes	471:541	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	7	80	from	position	1159:1166	arg1	acids					1143:1147	most amino acids	1132:1147	most amino acids at the P1 position	1132:1166	We show that IMPa has no specific P1 residue preference and can tolerate most amino acids at the P1 position, except aspartic acid.
34962767	2	81	theme	adjacent	410:417	arg1	protein					402:408	the protein	398:408	the protein adjacent to the appended glycan	398:440	Recently, several O-glycan-specific endoproteases that can cleave the protein adjacent to the appended glycan have been described.
34962767	0	82	theme	Improved	49:56	arg1	Analysis					58:65	Improved Analysis	49:65	Improved Analysis of Glycoproteins and Glycopeptides	49:100	A Broad-Specificity O-Glycoprotease That Enables Improved Analysis of Glycoproteins and Glycopeptides Containing Intact Complex O-Glycans.
34962767	11	83	theme	granulocyte	1673:1683	arg1	glycoproteins					1659:1671	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C	1646:1758	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1646:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	83	theme	granulocyte	1673:1683	arg1	factor					1704:1709	granulocyte colony-stimulating factor	1673:1709	granulocyte colony-stimulating factor	1673:1709	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	84	gly	glycoproteins	1659:1671	arg1	glycoproteins					1659:1671	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C	1646:1758	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1646:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	84	gly	glycoproteins	1659:1671	arg1	factor					1704:1709	granulocyte colony-stimulating factor	1673:1709	granulocyte colony-stimulating factor	1673:1709	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	84	gly	glycoproteins	1659:1671	arg1	C					1758:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	85	theme	purified	1650:1657	arg1	glycoproteins					1659:1671	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C	1646:1758	the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment	1646:1803	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	85	theme	purified	1650:1657	arg1	factor					1704:1709	granulocyte colony-stimulating factor	1673:1709	granulocyte colony-stimulating factor	1673:1709	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	11	85	theme	purified	1650:1657	arg1	C					1758:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	receptor-type tyrosine-protein phosphatase C	1715:1758	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	3	86	theme	known	544:548	arg1	O-glycoproteases					550:565	known O-glycoproteases	544:565	known O-glycoproteases	544:565	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	6	87	theme	Peptide	921:927	arg1	selectivity					938:948	Peptide sequence selectivity	921:948	Peptide sequence selectivity	921:948	Peptide sequence selectivity and its impact on IMPa activity were interrogated using an array of synthetic peptides and their glycoforms.
34962767	3	88	theme	protein	729:735	arg1	bias					746:749	protein sequence bias	729:749	protein sequence bias	729:749	Despite significant progress in understanding the biochemistry of these enzymes, known O-glycoproteases have specificity constraints, such as inefficient cleavage of glycoproteins bearing sialylated O-glycans, high selectivity for certain types of glycoproteins, or protein sequence bias.
34962767	11	89	theme	receptor-type	1715:1727	arg1	phosphatase					1746:1756	receptor-type tyrosine-protein phosphatase	1715:1756	receptor-type tyrosine-protein phosphatase C	1715:1758	We present the use of IMPa in a one-step O-glycoproteomic workflow for glycoprofiling of the purified glycoproteins granulocyte colony-stimulating factor and receptor-type tyrosine-protein phosphatase C without the need for glycopeptide enrichment.
34962767	2	90	theme	O-glycan-specific	350:366	arg1	endoproteases					368:380	several O-glycan-specific endoproteases	342:380	several O-glycan-specific endoproteases that can cleave the protein adjacent to the appended glycan	342:440	Recently, several O-glycan-specific endoproteases that can cleave the protein adjacent to the appended glycan have been described.
34962767	12	91	theme	complex	1895:1901	arg1	structures					1912:1921	complex O-glycan structures	1895:1921	complex O-glycan structures	1895:1921	In these examples, IMPa enabled both the identification of O-glycosites and the range of complex O-glycan structures at each site.
34232571	6	0	theme	complex	978:984	arg1	samples					1009:1015	complex biological or clinical samples	978:1015	complex biological or clinical samples	978:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	4	1	theme	glycans	611:617	arg1	analyses					545:552	comprehensive analyses	531:552	comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins	531:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	9	2	theme	Glycan	1245:1250	arg1	analysis					1266:1273	Glycan and glycosite analysis	1245:1273	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	6	3	theme	glycopeptides	959:971	arg1	enrichment					913:922	a high-throughput enrichment	895:922	a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples	895:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	4	4	theme	N-linked	624:631	arg1	glycoproteins					633:645	N-linked glycoproteins	624:645	N-linked glycoproteins	624:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	9	5	theme	glycosite	1256:1264	arg1	analysis					1266:1273	Glycan and glycosite analysis	1245:1273	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	5	6	theme	handling	668:675	arg1	systems					677:683	liquid handling systems	661:683	liquid handling systems	661:683	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	1	7	theme	common	169:174	arg1	modifications					188:200	the most common and diverse modifications	160:200	the most common and diverse modifications	160:200	Protein glycosylation is one of the most common and diverse modifications.
34232571	6	8	theme	glycosites	936:945	arg1	enrichment					913:922	a high-throughput enrichment	895:922	a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples	895:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	4	9	from	detail	509:514	arg1	protocol					496:503	this protocol	491:503	this protocol	491:503	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	1	10	theme	diverse	180:186	arg1	modifications					188:200	the most common and diverse modifications	160:200	the most common and diverse modifications	160:200	Protein glycosylation is one of the most common and diverse modifications.
34232571	3	11	theme	High-throughput	288:302	arg1	characterization					322:337	High-throughput and comprehensive characterization	288:337	High-throughput and comprehensive characterization of glycoproteins	288:354	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	8	12	theme	Periodicals	1075:1085	arg1	LLC					1087:1089	Wiley Periodicals LLC	1069:1089	Wiley Periodicals LLC	1069:1089	Current Protocols published by Wiley Periodicals LLC.
34232571	9	13	dep	Protocol	1098:1105	arg1	digestion					1120:1128	Enzymatic digestion	1110:1128	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	5	14	theme	sample	760:765	arg1	time					778:781	sample processing time	760:781	sample processing time	760:781	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	3	15	from	studies	397:403	arg1	processes					477:485	biological, physiological, and pathological processes	433:485	biological, physiological, and pathological processes	433:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	3	16	theme	comprehensive	308:320	arg1	characterization					322:337	High-throughput and comprehensive characterization	288:337	High-throughput and comprehensive characterization of glycoproteins	288:354	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	9	17	theme	Basic	1092:1096	arg1	Protocol					1098:1105	Basic Protocol 1	1092:1107	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	5	18	theme	high-throughput	722:736	arg1	manner					738:743	a high-throughput manner	720:743	a high-throughput manner	720:743	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	4	19	gly	glycopeptides	564:576	arg2	glycopeptides					564:576	intact glycopeptides	557:576	intact glycopeptides (IGPs)	557:583	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	19	gly	glycopeptides	564:576	arg1	glycoproteins					633:645	N-linked glycoproteins	624:645	N-linked glycoproteins	624:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	19	gly	glycopeptides	564:576	arg2	IGPs					579:582	IGPs	579:582	IGPs	579:582	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	7	20	dep	Authors	1029:1035	arg1	2021					1020:1023	© 2021	1018:1023	© 2021	1018:1023	© 2021 The Authors.
34232571	0	21	theme	Intact	53:58	arg1	Glycopeptides					60:72	Intact Glycopeptides	53:72	Intact Glycopeptides	53:72	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	4	22	theme	comprehensive	531:543	arg1	analyses					545:552	comprehensive analyses	531:552	comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins	531:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	9	23	theme	Enzymatic	1110:1118	arg1	digestion					1120:1128	Enzymatic digestion	1110:1128	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	4	24	from	glycoproteins	633:645	arg1	IGPs					579:582	IGPs	579:582	IGPs	579:582	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	24	from	glycoproteins	633:645	arg1	analyses					545:552	comprehensive analyses	531:552	comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins	531:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	24	from	glycoproteins	633:645	arg1	glycopeptides					564:576	intact glycopeptides	557:576	intact glycopeptides (IGPs)	557:583	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	24	from	glycoproteins	633:645	arg1	sites					600:604	glycosylation sites	586:604	glycosylation sites	586:604	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	24	from	glycoproteins	633:645	arg1	glycans					611:617	glycans	611:617	glycans from N-linked glycoproteins	611:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	25	gly	glycoproteins	633:645	arg1	glycoproteins					633:645	N-linked glycoproteins	624:645	N-linked glycoproteins	624:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	7	26	theme	©	1018:1018	arg1	2021					1020:1023	© 2021	1018:1023	© 2021	1018:1023	© 2021 The Authors.
34232571	5	27	theme	human	787:791	arg1	error					793:797	human error	787:797	human error	787:797	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	0	28	theme	Glycosites	37:46	arg1	Analyses					16:23	High-Throughput Analyses	0:23	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides	0:72	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	9	29	theme	Basic	1161:1165	arg1	Protocol					1167:1174	C4-tips Basic Protocol 2	1153:1176	C4-tips Basic Protocol 2	1153:1176	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	3	30	theme	pathological	464:475	arg1	processes					477:485	biological, physiological, and pathological processes	433:485	biological, physiological, and pathological processes	433:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	0	31	theme	High-Throughput	0:14	arg1	Analyses					16:23	High-Throughput Analyses	0:23	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides	0:72	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	3	32	theme	altered	408:414	arg1	glycosylation					416:428	altered glycosylation	408:428	altered glycosylation in biological, physiological, and pathological processes	408:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	9	33	gly	glycoproteins	1133:1145	arg1	glycoproteins					1133:1145	glycoproteins	1133:1145	glycoproteins using C4-tips Basic Protocol 2	1133:1176	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	4	34	theme	sites	600:604	arg1	analyses					545:552	comprehensive analyses	531:552	comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins	531:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	9	35	theme	Intact	1179:1184	arg1	analysis					1199:1206	Intact glycopeptide analysis	1179:1206	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	5	36	theme	sample	834:839	arg1	techniques					852:861	traditional proteomics sample processing techniques	811:861	traditional proteomics sample processing techniques	811:861	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	4	37	theme	glycopeptides	564:576	arg1	analyses					545:552	comprehensive analyses	531:552	comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins	531:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	38	link	N-linked	624:631	arg1	glycoproteins					633:645	N-linked glycoproteins	624:645	N-linked glycoproteins	624:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	2	39	theme	Aberrant	203:210	arg1	glycosylation					220:232	Aberrant protein glycosylation	203:232	Aberrant protein glycosylation	203:232	Aberrant protein glycosylation has been reported to associate with various diseases.
34232571	9	40	theme	C18/MAX-tips	1214:1225	arg1	Protocol					1233:1240	C18/MAX-tips Basic Protocol 3	1214:1242	C18/MAX-tips Basic Protocol 3	1214:1242	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	9	41	dep	digestion	1120:1128	arg1	analysis					1266:1273	Glycan and glycosite analysis	1245:1273	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	9	41	dep	digestion	1120:1128	arg1	analysis					1199:1206	Intact glycopeptide analysis	1179:1206	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	3	42	from	processes	477:485	arg1	studies					397:403	structural and functional studies	371:403	structural and functional studies of altered glycosylation in biological, physiological, and pathological processes	371:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	9	43	gly	glycopeptide	1186:1197	arg2	glycopeptide					1186:1197	Intact glycopeptide analysis	1179:1206	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	6	44	theme	biological	986:995	arg1	samples					1009:1015	complex biological or clinical samples	978:1015	complex biological or clinical samples	978:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	8	45	theme	Current	1038:1044	arg1	Protocols					1046:1054	Current Protocols	1038:1054	Current Protocols	1038:1054	Current Protocols published by Wiley Periodicals LLC.
34232571	4	46	from	analyses	545:552	arg1	glycoproteins					633:645	N-linked glycoproteins	624:645	N-linked glycoproteins	624:645	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	6	47	theme	intact	952:957	arg1	glycopeptides					959:971	intact glycopeptides	952:971	intact glycopeptides	952:971	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	5	48	theme	liquid	661:666	arg1	systems					677:683	liquid handling systems	661:683	liquid handling systems	661:683	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	8	49	theme	Wiley	1069:1073	arg1	LLC					1087:1089	Wiley Periodicals LLC	1069:1089	Wiley Periodicals LLC	1069:1089	Current Protocols published by Wiley Periodicals LLC.
34232571	5	50	theme	traditional	811:821	arg1	techniques					852:861	traditional proteomics sample processing techniques	811:861	traditional proteomics sample processing techniques	811:861	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	6	51	theme	high-throughput	897:911	arg1	enrichment					913:922	a high-throughput enrichment	895:922	a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples	895:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	1	52	theme	modifications	188:200	arg1	one					153:155	one	153:155	one	153:155	Protein glycosylation is one of the most common and diverse modifications.
34232571	1	52	theme	modifications	188:200	arg1	modifications					188:200	the most common and diverse modifications	160:200	the most common and diverse modifications	160:200	Protein glycosylation is one of the most common and diverse modifications.
34232571	9	53	gly	glycosite	1256:1264	arg2	glycosite					1256:1264	glycosite	1256:1264	glycosite	1256:1264	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	4	54	gly	glycosylation	586:598	arg2	sites					600:604	glycosylation sites	586:604	glycosylation sites	586:604	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	6	55	theme	clinical	1000:1007	arg1	samples					1009:1015	complex biological or clinical samples	978:1015	complex biological or clinical samples	978:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	3	56	theme	glycoproteins	342:354	arg1	characterization					322:337	High-throughput and comprehensive characterization	288:337	High-throughput and comprehensive characterization of glycoproteins	288:354	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	2	57	theme	various	270:276	arg1	diseases					278:285	various diseases	270:285	various diseases	270:285	Aberrant protein glycosylation has been reported to associate with various diseases.
34232571	1	58	theme	Protein	128:134	arg1	glycosylation					136:148	Protein glycosylation	128:148	Protein glycosylation	128:148	Protein glycosylation is one of the most common and diverse modifications.
34232571	6	59	gly	glycosites	936:945	arg2	glycosites					936:945	glycosites	936:945	glycosites	936:945	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	0	60	theme	Glycopeptides	60:72	arg1	Analyses					16:23	High-Throughput Analyses	0:23	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides	0:72	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	3	61	theme	structural	371:380	arg1	studies					397:403	structural and functional studies	371:403	structural and functional studies of altered glycosylation in biological, physiological, and pathological processes	371:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	0	62	theme	C4-and	80:85	arg1	C18/MAX-Tips					87:98	C4-and C18/MAX-Tips and Liquid Handling System	80:125	C18/MAX-Tips	87:98	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	4	63	theme	intact	557:562	arg1	IGPs					579:582	IGPs	579:582	IGPs	579:582	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	4	63	theme	intact	557:562	arg1	glycopeptides					564:576	intact glycopeptides	557:576	intact glycopeptides (IGPs)	557:583	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	6	64	gly	glycopeptides	959:971	arg2	glycopeptides					959:971	intact glycopeptides	952:971	intact glycopeptides	952:971	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	5	65	theme	processing	767:776	arg1	time					778:781	sample processing time	760:781	sample processing time	760:781	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	9	66	theme	glycoproteins	1133:1145	arg1	digestion					1120:1128	Enzymatic digestion	1110:1128	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	0	67	theme	Handling	111:118	arg1	System					120:125	C4-and C18/MAX-Tips and Liquid Handling System	80:125	System	120:125	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	3	68	from	glycosylation	416:428	arg1	processes					477:485	biological, physiological, and pathological processes	433:485	biological, physiological, and pathological processes	433:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	3	69	theme	functional	386:395	arg1	studies					397:403	structural and functional studies	371:403	structural and functional studies of altered glycosylation in biological, physiological, and pathological processes	371:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	9	70	theme	C4-tips	1153:1159	arg1	Protocol					1167:1174	C4-tips Basic Protocol 2	1153:1176	C4-tips Basic Protocol 2	1153:1176	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	3	71	gly	glycosylation	416:428	arg1	processes					477:485	biological, physiological, and pathological processes	433:485	biological, physiological, and pathological processes	433:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	3	72	theme	biological	433:442	arg1	processes					477:485	biological, physiological, and pathological processes	433:485	biological, physiological, and pathological processes	433:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	4	73	theme	glycosylation	586:598	arg1	sites					600:604	glycosylation sites	586:604	glycosylation sites	586:604	In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins.
34232571	0	74	theme	Glycans	28:34	arg1	Analyses					16:23	High-Throughput Analyses	0:23	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides	0:72	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	3	75	theme	glycosylation	416:428	arg1	studies					397:403	structural and functional studies	371:403	structural and functional studies of altered glycosylation in biological, physiological, and pathological processes	371:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	5	76	theme	proteomics	823:832	arg1	techniques					852:861	traditional proteomics sample processing techniques	811:861	traditional proteomics sample processing techniques	811:861	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	6	77	theme	glycans	927:933	arg1	enrichment					913:922	a high-throughput enrichment	895:922	a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples	895:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	9	78	theme	glycopeptide	1186:1197	arg1	analysis					1199:1206	Intact glycopeptide analysis	1179:1206	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.	1092:1274	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	0	79	theme	Liquid	104:109	arg1	System					120:125	C4-and C18/MAX-Tips and Liquid Handling System	80:125	System	120:125	High-Throughput Analyses of Glycans, Glycosites, and Intact Glycopeptides Using C4-and C18/MAX-Tips and Liquid Handling System.
34232571	5	80	theme	processing	841:850	arg1	techniques					852:861	traditional proteomics sample processing techniques	811:861	traditional proteomics sample processing techniques	811:861	By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques.
34232571	3	81	theme	physiological	445:457	arg1	processes					477:485	biological, physiological, and pathological processes	433:485	biological, physiological, and pathological processes	433:485	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
34232571	2	82	theme	protein	212:218	arg1	glycosylation					220:232	Aberrant protein glycosylation	203:232	Aberrant protein glycosylation	203:232	Aberrant protein glycosylation has been reported to associate with various diseases.
34232571	6	83	from	samples	1009:1015	arg1	enrichment					913:922	a high-throughput enrichment	895:922	a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples	895:1015	Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples.
34232571	9	84	theme	Basic	1227:1231	arg1	Protocol					1233:1240	C18/MAX-tips Basic Protocol 3	1214:1242	C18/MAX-tips Basic Protocol 3	1214:1242	Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.
34232571	3	85	gly	glycoproteins	342:354	arg1	glycoproteins					342:354	glycoproteins	342:354	glycoproteins	342:354	High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes.
32707739	0	0	theme	Glutamate	87:95	arg1	Receptor					97:104	AMPA-Type Glutamate Receptor	77:104	AMPA-Type Glutamate Receptor	77:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	7	1	theme	expression	1211:1220	arg1	level					1222:1226	the cell surface expression level	1194:1226	the cell surface expression level of GluA1WT	1194:1237	Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT.
32707739	1	2	from	abundance	317:325	arg1	synapse					334:340	the synapse	330:340	the synapse	330:340	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	8	3	contain	have	1297:1300	arg1	N-glycans					1287:1295	these N-glycans	1281:1295	these N-glycans	1281:1295	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	8	3	contain	have	1297:1300	arg2	roles					1311:1315	distinct roles	1302:1315	distinct roles	1302:1315	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	0	4	theme	AMPA-Type	77:85	arg1	Receptor					97:104	AMPA-Type Glutamate Receptor	77:104	AMPA-Type Glutamate Receptor	77:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	3	5	theme	homo-oligomers	670:683	arg1	ER-exit					659:665	the ER-exit	655:665	the ER-exit of homo-oligomers	655:683	Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear.
32707739	4	6	from	GluA1N63/N363	758:770	arg1	N-glycans					745:753	N-glycans	745:753	N-glycans at GluA1N63/N363 and GluA2N370	745:784	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	4	6	from	GluA1N63/N363	758:770	arg1	role					737:740	the role	733:740	the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit	733:795	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	2	7	theme	cell	515:518	arg1	membrane					520:527	the cell membrane	511:527	the cell membrane	511:527	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	8	8	theme	GluA1	1335:1339	arg1	homo-oligomers					1351:1364	GluA1 and GluA2 homo-oligomers	1335:1364	GluA1 and GluA2 homo-oligomers	1335:1364	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	5	9	theme	GluA2N370Q	1019:1028	arg1	levels					994:999	the cell surface expression levels	966:999	the cell surface expression levels of GluA1N363Q and GluA2N370Q	966:1028	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	4	10	theme	N-glycans	745:753	arg1	role					737:740	the role	733:740	the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit	733:795	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	3	11	from	N-glycosylation	539:553	arg1	subunits					574:581	different AMPAR subunits	558:581	different AMPAR subunits	558:581	Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear.
32707739	0	12	theme	Receptor	97:104	arg1	Mutants					66:72	N-Glycosylation Site Mutants	45:72	N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	45:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	8	13	from	GluA1N63	1379:1386	arg1	prerequisite					1393:1404	a prerequisite	1391:1404	a prerequisite for GluA1 ER-exit	1391:1422	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	8	13	from	GluA1N63	1379:1386	arg1	N-glycan					1367:1374	N-glycan	1367:1374	N-glycan at GluA1N63	1367:1386	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	1	14	theme	subunits	289:296	arg1	combinations					268:279	various combinations	260:279	various combinations of four subunits (GluA1-4)	260:306	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	0	15	theme	Homo-Oligomeric	116:130	arg1	Conditions					143:152	the Homo-Oligomeric Expression Conditions	112:152	the Homo-Oligomeric Expression Conditions	112:152	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	8	16	theme	GluA2	1345:1349	arg1	homo-oligomers					1351:1364	GluA1 and GluA2 homo-oligomers	1335:1364	GluA1 and GluA2 homo-oligomers	1335:1364	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	3	17	from	role	647:650	arg1	ER-exit					659:665	the ER-exit	655:665	the ER-exit of homo-oligomers	655:683	Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear.
32707739	1	18	theme	synaptic	369:376	arg1	activity					378:385	synaptic activity	369:385	synaptic activity	369:385	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	4	19	from	role	737:740	arg1	ER-exit					789:795	ER-exit	789:795	ER-exit	789:795	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	4	19	from	role	737:740	arg1	GluA2N370					776:784	GluA2N370	776:784	GluA2N370	776:784	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	4	19	from	role	737:740	arg1	GluA1N63/N363					758:770	GluA1N63/N363	758:770	GluA1N63/N363	758:770	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	5	20	theme	cell	970:973	arg1	levels					994:999	the cell surface expression levels	966:999	the cell surface expression levels of GluA1N363Q and GluA2N370Q	966:1028	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	8	21	from	GluA2N370	1460:1468	arg1	N-glycans					1433:1441	N-glycans	1433:1441	N-glycans at GluA1N363 and GluA2N370	1433:1468	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	6	22	theme	wild-type	1075:1083	arg1	GluA1					1090:1094	wild-type (WT) GluA1	1075:1094	wild-type (WT) GluA1	1075:1094	Unlike wild-type (WT) GluA1, GluA2WT rescued surface GluA2N370Q expression.
32707739	0	23	theme	Cell	9:12	arg1	Patterns					33:40	Distinct Cell Surface Expression Patterns	0:40	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	0:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	1	24	theme	activity	378:385	arg1	strength					357:364	the strength	353:364	the strength of synaptic activity	353:385	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	3	25	theme	AMPAR	568:572	arg1	subunits					574:581	different AMPAR subunits	558:581	different AMPAR subunits	558:581	Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear.
32707739	4	26	theme	low	878:880	arg1	expressions					895:905	low cell surface expressions	878:905	low cell surface expressions	878:905	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	0	27	theme	Distinct	0:7	arg1	Patterns					33:40	Distinct Cell Surface Expression Patterns	0:40	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	0:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	5	28	theme	N-glycosylation	927:941	arg1	mutant					948:953	the N-glycosylation site mutant GluA1N63Q	923:963	the N-glycosylation site mutant GluA1N63Q	923:963	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	0	29	theme	Expression	22:31	arg1	Patterns					33:40	Distinct Cell Surface Expression Patterns	0:40	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	0:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	4	30	theme	homo-oligomeric	807:821	arg1	conditions					834:843	the homo-oligomeric expression conditions	803:843	the homo-oligomeric expression conditions	803:843	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	5	31	theme	site	943:946	arg1	mutant					948:953	the N-glycosylation site mutant GluA1N63Q	923:963	the N-glycosylation site mutant GluA1N63Q	923:963	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	1	32	theme	homotetrameric	201:214	arg1	channel					240:246	a homotetrameric or heterotetrameric ion channel	199:246	a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4)	199:306	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	32	theme	homotetrameric	201:214	arg1	receptor					179:186	The AMPA-type glutamate receptor	155:186	The AMPA-type glutamate receptor (AMPAR)	155:194	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	0	33	theme	Surface	14:20	arg1	Patterns					33:40	Distinct Cell Surface Expression Patterns	0:40	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	0:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	0	34	theme	Expression	132:141	arg1	Conditions					143:152	the Homo-Oligomeric Expression Conditions	112:152	the Homo-Oligomeric Expression Conditions	112:152	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	3	35	theme	different	558:566	arg1	subunits					574:581	different AMPAR subunits	558:581	different AMPAR subunits	558:581	Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear.
32707739	3	36	gly	N-glycosylation	539:553	arg1	subunits					574:581	different AMPAR subunits	558:581	different AMPAR subunits	558:581	Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear.
32707739	2	37	theme	AMPAR	466:470	arg1	ER-exit					482:488	ER-exit	482:488	ER-exit	482:488	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	37	theme	AMPAR	466:470	arg1	subunits					472:479	AMPAR subunits	466:479	AMPAR subunits' ER-exit and translocation to the cell membrane	466:527	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	37	theme	AMPAR	466:470	arg1	translocation					494:506	translocation	494:506	translocation to the cell membrane	494:527	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	7	38	theme	GluA1N63Q	1176:1184	arg1	expression					1162:1171	the expression	1158:1171	the expression of GluA1N63Q	1158:1184	Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT.
32707739	5	39	theme	GluA1N363Q	1004:1013	arg1	levels					994:999	the cell surface expression levels	966:999	the cell surface expression levels of GluA1N363Q and GluA2N370Q	966:1028	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	1	40	theme	heterotetrameric	219:234	arg1	channel					240:246	a homotetrameric or heterotetrameric ion channel	199:246	a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4)	199:306	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	40	theme	heterotetrameric	219:234	arg1	receptor					179:186	The AMPA-type glutamate receptor	155:186	The AMPA-type glutamate receptor (AMPAR)	155:194	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	3	41	theme	hetero-oligomers	625:640	arg1	ER-exit					614:620	the ER-exit	610:620	the ER-exit of hetero-oligomers	610:640	Although N-glycosylation on different AMPAR subunits has been shown to regulate the ER-exit of hetero-oligomers, its role in the ER-exit of homo-oligomers remains unclear.
32707739	1	42	theme	ion	236:238	arg1	channel					240:246	a homotetrameric or heterotetrameric ion channel	199:246	a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4)	199:306	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	42	theme	ion	236:238	arg1	receptor					179:186	The AMPA-type glutamate receptor	155:186	The AMPA-type glutamate receptor (AMPAR)	155:194	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	0	43	theme	Site	61:64	arg1	Mutants					66:72	N-Glycosylation Site Mutants	45:72	N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	45:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	5	44	gly	N-glycosylation	927:941	arg2	mutant					948:953	the N-glycosylation site mutant GluA1N63Q	923:963	the N-glycosylation site mutant GluA1N63Q	923:963	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	5	44	gly	N-glycosylation	927:941	arg2	site					943:946	the N-glycosylation site mutant GluA1N63Q	923:963	the N-glycosylation site mutant GluA1N63Q	923:963	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	4	45	theme	cell	882:885	arg1	expressions					895:905	low cell surface expressions	878:905	low cell surface expressions	878:905	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	7	46	theme	GluA1WT	1231:1237	arg1	level					1222:1226	the cell surface expression level	1194:1226	the cell surface expression level of GluA1WT	1194:1237	Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT.
32707739	4	47	theme	expression	823:832	arg1	conditions					834:843	the homo-oligomeric expression conditions	803:843	the homo-oligomeric expression conditions	803:843	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	8	48	theme	homo-oligomers	1351:1364	arg1	ER-exit					1324:1330	the ER-exit	1320:1330	the ER-exit of GluA1 and GluA2 homo-oligomers	1320:1364	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	6	49	theme	GluA2N370Q	1121:1130	arg1	expression					1132:1141	surface GluA2N370Q expression	1113:1141	surface GluA2N370Q expression	1113:1141	Unlike wild-type (WT) GluA1, GluA2WT rescued surface GluA2N370Q expression.
32707739	0	50	theme	N-Glycosylation	45:59	arg1	Mutants					66:72	N-Glycosylation Site Mutants	45:72	N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	45:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	2	51	dep	subunits	472:479	arg1	ER-exit					482:488	ER-exit	482:488	ER-exit	482:488	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	51	dep	subunits	472:479	arg1	subunits					472:479	AMPAR subunits	466:479	AMPAR subunits' ER-exit and translocation to the cell membrane	466:527	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	51	dep	subunits	472:479	arg1	translocation					494:506	translocation	494:506	translocation to the cell membrane	494:527	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	6	52	dep	wild-type	1075:1083	arg1	WT					1086:1087	WT	1086:1087	WT	1086:1087	Unlike wild-type (WT) GluA1, GluA2WT rescued surface GluA2N370Q expression.
32707739	0	53	dep	Patterns	33:40	arg1	Conditions					143:152	the Homo-Oligomeric Expression Conditions	112:152	the Homo-Oligomeric Expression Conditions	112:152	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	7	54	theme	surface	1203:1209	arg1	level					1222:1226	the cell surface expression level	1194:1226	the cell surface expression level of GluA1WT	1194:1237	Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT.
32707739	6	55	theme	surface	1113:1119	arg1	expression					1132:1141	surface GluA2N370Q expression	1113:1141	surface GluA2N370Q expression	1113:1141	Unlike wild-type (WT) GluA1, GluA2WT rescued surface GluA2N370Q expression.
32707739	8	56	theme	GluA1	1410:1414	arg1	ER-exit					1416:1422	GluA1 ER-exit	1410:1422	GluA1 ER-exit	1410:1422	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	5	57	theme	surface	975:981	arg1	levels					994:999	the cell surface expression levels	966:999	the cell surface expression levels of GluA1N363Q and GluA2N370Q	966:1028	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	2	58	from	formation	392:400	arg1	ER					447:448	ER	447:448	ER	447:448	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	58	from	formation	392:400	arg1	reticulum					436:444	the endoplasmatic reticulum	418:444	the endoplasmatic reticulum (ER)	418:449	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	8	59	theme	distinct	1302:1309	arg1	roles					1311:1315	distinct roles	1302:1315	distinct roles	1302:1315	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	7	60	theme	cell	1198:1201	arg1	level					1222:1226	the cell surface expression level	1194:1226	the cell surface expression level of GluA1WT	1194:1237	Additionally, the expression of GluA1N63Q reduced the cell surface expression level of GluA1WT.
32707739	4	61	theme	surface	887:893	arg1	expressions					895:905	low cell surface expressions	878:905	low cell surface expressions	878:905	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	5	62	theme	time-dependent	1045:1058	arg1	manner					1060:1065	a time-dependent manner	1043:1065	a time-dependent manner	1043:1065	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	5	63	theme	expression	983:992	arg1	levels					994:999	the cell surface expression levels	966:999	the cell surface expression levels of GluA1N363Q and GluA2N370Q	966:1028	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	8	64	theme	ER-exit	1482:1488	arg1	rate					1490:1493	the ER-exit rate	1478:1493	the ER-exit rate	1478:1493	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	5	65	dep	mutant	948:953	arg1	contrast					911:918	contrast	911:918	contrast	911:918	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	5	65	dep	mutant	948:953	arg1	GluA1N63Q					955:963	GluA1N63Q	955:963	GluA1N63Q	955:963	In contrast to the N-glycosylation site mutant GluA1N63Q, the cell surface expression levels of GluA1N363Q and GluA2N370Q increased in a time-dependent manner.
32707739	8	66	from	GluA1N363	1446:1454	arg1	N-glycans					1433:1441	N-glycans	1433:1441	N-glycans at GluA1N363 and GluA2N370	1433:1468	In conclusion, our findings suggest that these N-glycans have distinct roles in the ER-exit of GluA1 and GluA2 homo-oligomers; N-glycan at GluA1N63 is a prerequisite for GluA1 ER-exit, whereas N-glycans at GluA1N363 and GluA2N370 control the ER-exit rate.
32707739	2	67	theme	oligomers	405:413	arg1	formation					392:400	The formation	388:400	The formation of oligomers in the endoplasmatic reticulum (ER)	388:449	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	67	theme	oligomers	405:413	arg1	crucial					454:460	crucial	454:460	crucial	454:460	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	68	theme	endoplasmatic	422:434	arg1	ER					447:448	ER	447:448	ER	447:448	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	2	68	theme	endoplasmatic	422:434	arg1	reticulum					436:444	the endoplasmatic reticulum	418:444	the endoplasmatic reticulum (ER)	418:449	The formation of oligomers in the endoplasmatic reticulum (ER) is crucial for AMPAR subunits' ER-exit and translocation to the cell membrane.
32707739	1	69	theme	AMPA-type	159:167	arg1	AMPAR					189:193	AMPAR	189:193	AMPAR	189:193	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	69	theme	AMPA-type	159:167	arg1	receptor					179:186	The AMPA-type glutamate receptor	155:186	The AMPA-type glutamate receptor (AMPAR)	155:194	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	69	theme	AMPA-type	159:167	arg1	channel					240:246	a homotetrameric or heterotetrameric ion channel	199:246	a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4)	199:306	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	0	70	theme	Mutants	66:72	arg1	Patterns					33:40	Distinct Cell Surface Expression Patterns	0:40	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor	0:104	Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions.
32707739	4	71	from	GluA2N370	776:784	arg1	N-glycans					745:753	N-glycans	745:753	N-glycans at GluA1N63/N363 and GluA2N370	745:784	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	4	71	from	GluA2N370	776:784	arg1	role					737:740	the role	733:740	the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit	733:795	In this study, we investigated the role of N-glycans at GluA1N63/N363 and GluA2N370 in ER-exit under the homo-oligomeric expression conditions, whose mutants are known to show low cell surface expressions.
32707739	1	72	theme	glutamate	169:177	arg1	AMPAR					189:193	AMPAR	189:193	AMPAR	189:193	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	72	theme	glutamate	169:177	arg1	receptor					179:186	The AMPA-type glutamate receptor	155:186	The AMPA-type glutamate receptor (AMPAR)	155:194	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	72	theme	glutamate	169:177	arg1	channel					240:246	a homotetrameric or heterotetrameric ion channel	199:246	a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4)	199:306	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32707739	1	73	theme	various	260:266	arg1	combinations					268:279	various combinations	260:279	various combinations of four subunits (GluA1-4)	260:306	The AMPA-type glutamate receptor (AMPAR) is a homotetrameric or heterotetrameric ion channel composed of various combinations of four subunits (GluA1-4), and its abundance in the synapse determines the strength of synaptic activity.
32022078	5	0	theme	present	799:805	arg1	study					807:811	the present study	795:811	the present study	795:811	We are convinced that these data should be used in concert, as we demonstrate in the present study.
32022078	2	1	theme	different	382:390	arg1	techniques					398:407	different MS/MS techniques	382:407	different MS/MS techniques	382:407	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	6	2	theme	common	852:857	arg1	glycans					859:865	the most common glycans	843:865	the most common glycans	843:865	First, glycopeptides bearing the most common glycans can be identified from EThcD and/or HCD data.
32022078	2	3	gly	O-glycopeptides	207:221	arg2	O-glycopeptides					207:221	O-glycopeptides	207:221	O-glycopeptides	207:221	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	8	4	theme	tentative	1151:1159	arg1	assignments					1161:1171	the tentative assignments	1147:1171	the tentative assignments	1147:1171	Finally, these spectra and the corresponding EThcD data can be used to verify or discard the tentative assignments and to obtain further structural information about the glycans.
32022078	2	5	theme	certain	325:331	arg1	units					339:343	certain sugar units	325:343	certain sugar units	325:343	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	4	6	theme	different	652:660	arg1	data					668:671	the different MS/MS data	648:671	the different MS/MS data	648:671	However, the information content of the different MS/MS data is handled separately by search engines.
32022078	1	7	link	cross-linked	94:105	arg1	structures					107:116	cross-linked structures	94:116	cross-linked structures between chemically and physically different biomolecules	94:173	Glycopeptides represent cross-linked structures between chemically and physically different biomolecules.
32022078	0	8	link	O-linked	6:13	arg1	structures					27:36	Novel O-linked sialoglycan structures	0:36	Novel O-linked sialoglycan structures in human urinary glycoproteins	0:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	7	9	gly	deglycosylated	951:964	arg1	peptide					966:972	the gas-phase deglycosylated peptide	937:972	the gas-phase deglycosylated peptide	937:972	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	7	9	gly	deglycosylated	951:964	arg1	Y0					933:934	Y0	933:934	Y0 (the gas-phase deglycosylated peptide) in HCD spectra	933:988	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	3	10	theme	data	585:588	arg1	protocol					602:609	the most promising data acquisition protocol	566:609	the most promising data acquisition protocol	566:609	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	3	10	theme	data	585:588	arg1	analysis					481:488	HCD analysis	477:488	HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments	477:561	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	8	11	theme	further	1187:1193	arg1	information					1206:1216	further structural information	1187:1216	further structural information about the glycans	1187:1234	Finally, these spectra and the corresponding EThcD data can be used to verify or discard the tentative assignments and to obtain further structural information about the glycans.
32022078	2	12	theme	spectrometric	181:193	arg1	analysis					195:202	Mass spectrometric analysis	176:202	Mass spectrometric analysis of O-glycopeptides	176:221	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	7	13	theme	deglycosylated	951:964	arg1	peptide					966:972	the gas-phase deglycosylated peptide	937:972	the gas-phase deglycosylated peptide	937:972	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	7	13	theme	deglycosylated	951:964	arg1	Y0					933:934	Y0	933:934	Y0 (the gas-phase deglycosylated peptide) in HCD spectra	933:988	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	1	14	theme	cross-linked	94:105	arg1	structures					107:116	cross-linked structures	94:116	cross-linked structures between chemically and physically different biomolecules	94:173	Glycopeptides represent cross-linked structures between chemically and physically different biomolecules.
32022078	0	15	theme	O-linked	6:13	arg1	structures					27:36	Novel O-linked sialoglycan structures	0:36	Novel O-linked sialoglycan structures in human urinary glycoproteins	0:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	2	16	theme	Mass	176:179	arg1	analysis					195:202	Mass spectrometric analysis	176:202	Mass spectrometric analysis of O-glycopeptides	176:221	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	2	17	theme	sufficient	418:427	arg1	information					429:439	sufficient information	418:439	sufficient information for reliable assignment	418:463	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	0	18	theme	Novel	0:4	arg1	structures					27:36	Novel O-linked sialoglycan structures	0:36	Novel O-linked sialoglycan structures in human urinary glycoproteins	0:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	7	19	gly	glycoforms	1005:1014	arg1	glycopeptides					1025:1037	these glycopeptides	1019:1037	these glycopeptides	1019:1037	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	9	20	theme	sialoglycan	1271:1281	arg1	structures					1283:1292	18 novel human urinary sialoglycan structures	1248:1292	18 novel human urinary sialoglycan structures deciphered using this approach	1248:1323	We present 18 novel human urinary sialoglycan structures deciphered using this approach.
32022078	9	21	theme	novel	1251:1255	arg1	structures					1283:1292	18 novel human urinary sialoglycan structures	1248:1292	18 novel human urinary sialoglycan structures deciphered using this approach	1248:1323	We present 18 novel human urinary sialoglycan structures deciphered using this approach.
32022078	3	22	theme	HCD	477:479	arg1	analysis					481:488	HCD analysis	477:488	HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments	477:561	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	3	22	theme	HCD	477:479	arg1	protocol					602:609	the most promising data acquisition protocol	566:609	the most promising data acquisition protocol	566:609	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	8	23	theme	structural	1195:1204	arg1	information					1206:1216	further structural information	1187:1216	further structural information about the glycans	1187:1234	Finally, these spectra and the corresponding EThcD data can be used to verify or discard the tentative assignments and to obtain further structural information about the glycans.
32022078	6	24	gly	glycopeptides	821:833	arg2	glycopeptides					821:833	glycopeptides	821:833	glycopeptides bearing the most common glycans	821:865	First, glycopeptides bearing the most common glycans can be identified from EThcD and/or HCD data.
32022078	7	25	theme	gas-phase	941:949	arg1	peptide					966:972	the gas-phase deglycosylated peptide	937:972	the gas-phase deglycosylated peptide	937:972	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	7	25	theme	gas-phase	941:949	arg1	Y0					933:934	Y0	933:934	Y0 (the gas-phase deglycosylated peptide) in HCD spectra	933:988	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	7	26	from	Y0	933:934	arg1	spectra					982:988	HCD spectra	978:988	HCD spectra	978:988	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	7	27	theme	HCD	978:980	arg1	spectra					982:988	HCD spectra	978:988	HCD spectra	978:988	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	3	28	theme	sugar	513:517	arg1	ETD					538:540	diagnostic sugar fragment-triggered ETD	502:540	diagnostic sugar fragment-triggered ETD	502:540	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	0	29	theme	sialoglycan	15:25	arg1	structures					27:36	Novel O-linked sialoglycan structures	0:36	Novel O-linked sialoglycan structures in human urinary glycoproteins	0:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	4	30	theme	information	625:635	arg1	content					637:643	the information content	621:643	the information content of the different MS/MS data	621:671	However, the information content of the different MS/MS data is handled separately by search engines.
32022078	6	31	theme	HCD	903:905	arg1	data					907:910	HCD data	903:910	HCD data	903:910	First, glycopeptides bearing the most common glycans can be identified from EThcD and/or HCD data.
32022078	2	32	theme	sugar	333:337	arg1	units					339:343	certain sugar units	325:343	certain sugar units	325:343	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	3	33	theme	fragment-triggered	519:536	arg1	ETD					538:540	diagnostic sugar fragment-triggered ETD	502:540	diagnostic sugar fragment-triggered ETD	502:540	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	0	34	theme	human	41:45	arg1	glycoproteins					55:67	human urinary glycoproteins	41:67	human urinary glycoproteins	41:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	8	35	theme	EThcD	1103:1107	arg1	data					1109:1112	the corresponding EThcD data	1085:1112	the corresponding EThcD data	1085:1112	Finally, these spectra and the corresponding EThcD data can be used to verify or discard the tentative assignments and to obtain further structural information about the glycans.
32022078	4	36	theme	search	698:703	arg1	engines					705:711	search engines	698:711	search engines	698:711	However, the information content of the different MS/MS data is handled separately by search engines.
32022078	8	37	used	used	1121:1124	arg2	spectra					1073:1079	these spectra	1067:1079	these spectra	1067:1079	Finally, these spectra and the corresponding EThcD data can be used to verify or discard the tentative assignments and to obtain further structural information about the glycans.
32022078	8	37	used	used	1121:1124	arg2	data					1109:1112	the corresponding EThcD data	1085:1112	the corresponding EThcD data	1085:1112	Finally, these spectra and the corresponding EThcD data can be used to verify or discard the tentative assignments and to obtain further structural information about the glycans.
32022078	8	38	theme	corresponding	1089:1101	arg1	data					1109:1112	the corresponding EThcD data	1085:1112	the corresponding EThcD data	1085:1112	Finally, these spectra and the corresponding EThcD data can be used to verify or discard the tentative assignments and to obtain further structural information about the glycans.
32022078	7	39	theme	glycopeptides	1025:1037	arg1	glycoforms					1005:1014	the potential glycoforms	991:1014	the potential glycoforms of these glycopeptides	991:1037	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	2	40	theme	reliable	445:452	arg1	assignment					454:463	reliable assignment	445:463	reliable assignment	445:463	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	5	41	used	used	757:760	arg2	data					742:745	these data	736:745	these data	736:745	We are convinced that these data should be used in concert, as we demonstrate in the present study.
32022078	7	42	gly	glycopeptides	1025:1037	arg2	glycopeptides					1025:1037	these glycopeptides	1019:1037	these glycopeptides	1019:1037	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	2	43	theme	O-glycopeptides	207:221	arg1	analysis					195:202	Mass spectrometric analysis	176:202	Mass spectrometric analysis of O-glycopeptides	176:221	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	3	44	theme	EThcD	545:549	arg1	experiments					551:561	EThcD experiments	545:561	EThcD experiments	545:561	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	0	45	theme	urinary	47:53	arg1	glycoproteins					55:67	human urinary glycoproteins	41:67	human urinary glycoproteins	41:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	2	46	theme	peptide	254:260	arg1	composition					267:277	the composition	263:277	the composition of the glycan	263:291	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	2	46	theme	peptide	254:260	arg1	connection					306:315	even the connection	297:315	even the connection between certain sugar units	297:343	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	2	46	theme	peptide	254:260	arg1	identity					238:245	the identity	234:245	the identity of the peptide	234:260	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	1	47	theme	different	152:160	arg1	biomolecules					162:173	chemically and physically different biomolecules	126:173	chemically and physically different biomolecules	126:173	Glycopeptides represent cross-linked structures between chemically and physically different biomolecules.
32022078	9	48	theme	human	1257:1261	arg1	structures					1283:1292	18 novel human urinary sialoglycan structures	1248:1292	18 novel human urinary sialoglycan structures deciphered using this approach	1248:1323	We present 18 novel human urinary sialoglycan structures deciphered using this approach.
32022078	4	49	theme	data	668:671	arg1	content					637:643	the information content	621:643	the information content of the different MS/MS data	621:671	However, the information content of the different MS/MS data is handled separately by search engines.
32022078	3	50	theme	acquisition	590:600	arg1	protocol					602:609	the most promising data acquisition protocol	566:609	the most promising data acquisition protocol	566:609	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	3	50	theme	acquisition	590:600	arg1	analysis					481:488	HCD analysis	477:488	HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments	477:561	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	9	51	theme	urinary	1263:1269	arg1	structures					1283:1292	18 novel human urinary sialoglycan structures	1248:1292	18 novel human urinary sialoglycan structures deciphered using this approach	1248:1323	We present 18 novel human urinary sialoglycan structures deciphered using this approach.
32022078	10	52	theme	automated	1351:1359	arg1	fashion					1361:1367	an automated fashion	1348:1367	an automated fashion	1348:1367	To accomplish this in an automated fashion further software development is necessary.
32022078	7	53	theme	potential	995:1003	arg1	glycoforms					1005:1014	the potential glycoforms	991:1014	the potential glycoforms of these glycopeptides	991:1037	Then, searching for Y0 (the gas-phase deglycosylated peptide) in HCD spectra, the potential glycoforms of these glycopeptides could be lined up.
32022078	3	54	theme	promising	575:583	arg1	protocol					602:609	the most promising data acquisition protocol	566:609	the most promising data acquisition protocol	566:609	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	3	54	theme	promising	575:583	arg1	analysis					481:488	HCD analysis	477:488	HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments	477:561	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	4	55	theme	MS/MS	662:666	arg1	data					668:671	the different MS/MS data	648:671	the different MS/MS data	648:671	However, the information content of the different MS/MS data is handled separately by search engines.
32022078	3	56	theme	diagnostic	502:511	arg1	ETD					538:540	diagnostic sugar fragment-triggered ETD	502:540	diagnostic sugar fragment-triggered ETD	502:540	Currently, HCD analysis followed by diagnostic sugar fragment-triggered ETD or EThcD experiments is the most promising data acquisition protocol.
32022078	2	57	theme	glycan	286:291	arg1	composition					267:277	the composition	263:277	the composition of the glycan	263:291	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	2	57	theme	glycan	286:291	arg1	connection					306:315	even the connection	297:315	even the connection between certain sugar units	297:343	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	2	57	theme	glycan	286:291	arg1	identity					238:245	the identity	234:245	the identity of the peptide	234:260	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	10	58	theme	software	1377:1384	arg1	development					1386:1396	further software development	1369:1396	further software development	1369:1396	To accomplish this in an automated fashion further software development is necessary.
32022078	2	59	theme	techniques	398:407	arg1	combination					367:377	usually only the combination	350:377	usually only the combination of different MS/MS techniques	350:407	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	0	60	from	structures	27:36	arg1	glycoproteins					55:67	human urinary glycoproteins	41:67	human urinary glycoproteins	41:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	0	61	gly	glycoproteins	55:67	arg1	glycoproteins					55:67	human urinary glycoproteins	41:67	human urinary glycoproteins	41:67	Novel O-linked sialoglycan structures in human urinary glycoproteins.
32022078	10	62	theme	further	1369:1375	arg1	development					1386:1396	further software development	1369:1396	further software development	1369:1396	To accomplish this in an automated fashion further software development is necessary.
32022078	2	63	theme	MS/MS	392:396	arg1	techniques					398:407	different MS/MS techniques	382:407	different MS/MS techniques	382:407	Mass spectrometric analysis of O-glycopeptides may reveal the identity of the peptide, the composition of the glycan and even the connection between certain sugar units, but usually only the combination of different MS/MS techniques provides sufficient information for reliable assignment.
32022078	10	64	dep	necessary	1401:1409	arg1	accomplish					1329:1338	accomplish	1329:1338	To accomplish this in an automated fashion	1326:1367	To accomplish this in an automated fashion further software development is necessary.
33242084	1	0	link	Asparagine-linked	86:102	arg1	glycosylation					104:116	Asparagine-linked glycosylation	86:116	Asparagine-linked glycosylation (N-glycosylation)	86:134	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	0	link	Asparagine-linked	86:102	arg1	N-glycosylation					119:133	N-glycosylation	119:133	N-glycosylation	119:133	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	0	1	from	changes	25:31	arg1	composition					40:50	the composition	36:50	the composition of the rat neocortical N-glycome	36:83	Post-natal developmental changes in the composition of the rat neocortical N-glycome.
33242084	4	2	theme	neocortical	876:886	arg1	N-glycome					888:896	the adult neocortical N-glycome	866:896	the adult neocortical N-glycome	866:896	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	4	3	theme	24-	911:913	arg1	neonates					924:931	24- and 48-h neonates	911:931	24- and 48-h neonates	911:931	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	1	4	theme	many	156:159	arg1	adhesion					213:220	neural cell adhesion	201:220	neural cell adhesion	201:220	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	4	theme	many	156:159	arg1	processes					180:188	many neurodevelopmental processes	156:188	many neurodevelopmental processes	156:188	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	4	theme	many	156:159	arg1	targeting					250:258	axon targeting	245:258	axon targeting	245:258	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	4	theme	many	156:159	arg1	outgrowth					231:239	neurite outgrowth	223:239	neurite outgrowth	223:239	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	2	5	from	dynamics	296:303	arg1	particular					357:366	particular	357:366	particular	357:366	However, little is known about the dynamics of N-glycosylation during brain development and, in particular, how the N-glycome of the developing neocortex differs from that of the adult.
33242084	0	6	theme	N-glycome	75:83	arg1	composition					40:50	the composition	36:50	the composition of the rat neocortical N-glycome	36:83	Post-natal developmental changes in the composition of the rat neocortical N-glycome.
33242084	4	7	theme	adult	870:874	arg1	N-glycome					888:896	the adult neocortical N-glycome	866:896	the adult neocortical N-glycome	866:896	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	1	8	theme	neurodevelopmental	161:178	arg1	adhesion					213:220	neural cell adhesion	201:220	neural cell adhesion	201:220	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	8	theme	neurodevelopmental	161:178	arg1	processes					180:188	many neurodevelopmental processes	156:188	many neurodevelopmental processes	156:188	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	8	theme	neurodevelopmental	161:178	arg1	targeting					250:258	axon targeting	245:258	axon targeting	245:258	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	8	theme	neurodevelopmental	161:178	arg1	outgrowth					231:239	neurite outgrowth	223:239	neurite outgrowth	223:239	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	4	9	theme	mass	837:840	arg1	spectrometry					842:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	4	10	theme	interaction	725:735	arg1	chromatography					761:774	hydrophilic interaction ultraperformance liquid chromatography	713:774	hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry	713:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	9	11	dep	smaller	1732:1738	arg1	neutral					1741:1747	neutral	1741:1747	neutral	1741:1747	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	5	12	theme	complex	966:972	arg1	N-glycans					974:982	complex N-glycans	966:982	complex N-glycans	966:982	We report that the abundance of complex N-glycans is significantly lower in adults compared with neonates.
33242084	4	13	theme	hydrophilic	713:723	arg1	chromatography					761:774	hydrophilic interaction ultraperformance liquid chromatography	713:774	hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry	713:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	9	14	from	synthesis	1569:1577	arg1	neocortex					1590:1598	the rat neocortex	1582:1598	the rat neocortex	1582:1598	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	2	15	theme	brain	331:335	arg1	development					337:347	brain development	331:347	brain development	331:347	However, little is known about the dynamics of N-glycosylation during brain development and, in particular, how the N-glycome of the developing neocortex differs from that of the adult.
33242084	8	16	from	subtypes	1466:1473	arg1	neonates					1478:1485	neonates	1478:1485	neonates	1478:1485	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	9	17	from	different	1617:1625	arg1	neonates					1630:1637	neonates	1630:1637	neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures	1630:1861	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	4	18	used	used	708:711	arg2	we					705:706	we	705:706	we	705:706	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	4	19	theme	liquid	754:759	arg1	chromatography					761:774	hydrophilic interaction ultraperformance liquid chromatography	713:774	hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry	713:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	6	20	theme	N-glycans	1088:1096	arg1	proportion					1058:1067	the proportion	1054:1067	the proportion of charged complex N-glycans	1054:1096	Furthermore, the proportion of charged complex N-glycans is also greatly reduced.
33242084	7	21	theme	corresponding	1190:1202	arg1	increase					1204:1211	a corresponding increase	1188:1211	a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans	1188:1284	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	3	22	theme	thorough	498:505	arg1	characterization					507:522	a thorough characterization	496:522	a thorough characterization of N-glycosylation	496:541	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	9	23	from	neonates	1630:1637	arg1	different					1617:1625	different	1617:1625	different	1617:1625	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	6	24	theme	complex	1080:1086	arg1	N-glycans					1088:1096	charged complex N-glycans	1072:1096	charged complex N-glycans	1072:1096	Furthermore, the proportion of charged complex N-glycans is also greatly reduced.
33242084	0	25	theme	developmental	11:23	arg1	changes					25:31	Post-natal developmental changes	0:31	Post-natal developmental changes in the composition of the rat neocortical N-glycome.	0:84	Post-natal developmental changes in the composition of the rat neocortical N-glycome.
33242084	9	26	theme	general	1667:1673	arg1	shift					1675:1679	a general shift	1665:1679	a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures	1665:1861	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	9	27	dep	large	1696:1700	arg1	sialylated					1703:1712	sialylated	1703:1712	sialylated	1703:1712	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	1	28	theme	Asparagine-linked	86:102	arg1	glycosylation					104:116	Asparagine-linked glycosylation	86:116	Asparagine-linked glycosylation (N-glycosylation)	86:134	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	1	28	theme	Asparagine-linked	86:102	arg1	N-glycosylation					119:133	N-glycosylation	119:133	N-glycosylation	119:133	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	6	29	theme	charged	1072:1078	arg1	N-glycans					1088:1096	charged complex N-glycans	1072:1096	charged complex N-glycans	1072:1096	Furthermore, the proportion of charged complex N-glycans is also greatly reduced.
33242084	0	30	theme	Post-natal	0:9	arg1	changes					25:31	Post-natal developmental changes	0:31	Post-natal developmental changes in the composition of the rat neocortical N-glycome.	0:84	Post-natal developmental changes in the composition of the rat neocortical N-glycome.
33242084	2	31	theme	N-glycosylation	308:322	arg1	dynamics					296:303	the dynamics	292:303	the dynamics of N-glycosylation during brain development and, in particular	292:366	However, little is known about the dynamics of N-glycosylation during brain development and, in particular, how the N-glycome of the developing neocortex differs from that of the adult.
33242084	8	32	theme	oligomannose	1337:1348	arg1	N-glycans					1350:1358	oligomannose N-glycans	1337:1358	oligomannose N-glycans	1337:1358	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	1	33	theme	neural	201:206	arg1	adhesion					213:220	neural cell adhesion	201:220	neural cell adhesion	201:220	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	7	34	theme	N-glycans	1165:1173	arg1	abundance					1144:1152	the abundance	1140:1152	the abundance of complex N-glycans	1140:1173	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	8	35	theme	high-mannose	1412:1423	arg1	subtypes					1425:1432	high-mannose subtypes	1412:1432	high-mannose subtypes	1412:1432	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	3	36	theme	N-glycosylation	527:541	arg1	characterization					507:522	a thorough characterization	496:522	a thorough characterization of N-glycosylation	496:541	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	4	37	theme	quadrupole	811:820	arg1	spectrometry					842:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	1	38	theme	cell	208:211	arg1	adhesion					213:220	neural cell adhesion	201:220	neural cell adhesion	201:220	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	8	39	theme	N-glycans	1350:1358	arg1	proportion					1323:1332	the proportion	1319:1332	the proportion of oligomannose N-glycans	1319:1358	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	4	40	theme	48-h	919:922	arg1	neonates					924:931	24- and 48-h neonates	911:931	24- and 48-h neonates	911:931	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	9	41	dep	neonates	1763:1770	arg1	develop					1772:1778	develop	1772:1778	develop into adults	1772:1790	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	9	42	theme	parallel	1808:1815	arg1	shift					1817:1821	a parallel shift	1806:1821	a parallel shift towards smaller oligomannose structures	1806:1861	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	9	43	theme	large	1696:1700	arg1	N-glycans					1714:1722	large, sialylated N-glycans	1696:1722	large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures	1696:1861	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	8	44	theme	subtypes	1425:1432	arg1	distribution					1396:1407	the distribution	1392:1407	the distribution of high-mannose subtypes	1392:1432	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	3	45	theme	neonatal	565:572	arg1	neocortex					578:586	both the adult and neonatal rat neocortex	546:586	neocortex	578:586	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	2	46	theme	neocortex	405:413	arg1	N-glycome					377:385	the N-glycome	373:385	the N-glycome of the developing neocortex	373:413	However, little is known about the dynamics of N-glycosylation during brain development and, in particular, how the N-glycome of the developing neocortex differs from that of the adult.
33242084	7	47	theme	complex	1157:1163	arg1	N-glycans					1165:1173	complex N-glycans	1157:1173	complex N-glycans	1157:1173	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	7	48	from	increase	1204:1211	arg1	proportion					1220:1229	the proportion	1216:1229	the proportion of truncated and, to a lesser extent, hybrid N-glycans	1216:1284	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	3	49	theme	rat	574:576	arg1	neocortex					578:586	both the adult and neonatal rat neocortex	546:586	neocortex	578:586	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	2	50	theme	developing	394:403	arg1	neocortex					405:413	the developing neocortex	390:413	the developing neocortex	390:413	However, little is known about the dynamics of N-glycosylation during brain development and, in particular, how the N-glycome of the developing neocortex differs from that of the adult.
33242084	9	51	theme	smaller	1732:1738	arg1	structures					1749:1758	smaller, neutral structures	1732:1758	smaller, neutral structures	1732:1758	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	7	52	theme	truncated	1234:1242	arg1	proportion					1220:1229	the proportion	1216:1229	the proportion of truncated and, to a lesser extent, hybrid N-glycans	1216:1284	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	3	53	theme	adult	555:559	arg1	neocortex					578:586	both the adult and neonatal rat neocortex	546:586	neocortex	578:586	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	8	54	from	subtypes	1498:1505	arg1	adult					1514:1518	the adult	1510:1518	the adult	1510:1518	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	9	55	theme	smaller	1831:1837	arg1	structures					1852:1861	smaller oligomannose structures	1831:1861	smaller oligomannose structures	1831:1861	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	7	56	from	decrease	1128:1135	arg1	abundance					1144:1152	the abundance	1140:1152	the abundance of complex N-glycans	1140:1173	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	3	57	theme	changes	632:638	arg1	types					623:627	the types	619:627	the types of changes occurring in the N-glycome during neurodevelopment	619:689	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	4	58	theme	time-of-flight	822:835	arg1	spectrometry					842:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	7	59	theme	hybrid	1269:1274	arg1	N-glycans					1276:1284	hybrid N-glycans	1269:1284	hybrid N-glycans	1269:1284	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	9	60	theme	oligomannose	1839:1850	arg1	structures					1852:1861	smaller oligomannose structures	1831:1861	smaller oligomannose structures	1831:1861	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	9	61	theme	rat	1586:1588	arg1	neocortex					1590:1598	the rat neocortex	1582:1598	the rat neocortex	1582:1598	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	8	62	theme	large	1460:1464	arg1	subtypes					1466:1473	predominantly large subtypes	1446:1473	predominantly large subtypes in neonates	1446:1485	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	4	63	theme	ionization	800:809	arg1	spectrometry					842:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	7	64	theme	lesser	1254:1259	arg1	extent					1261:1266	a lesser extent	1252:1266	a lesser extent	1252:1266	This decrease in the abundance of complex N-glycans is offset by a corresponding increase in the proportion of truncated and, to a lesser extent, hybrid N-glycans.
33242084	9	65	theme	N-glycan	1560:1567	arg1	synthesis					1569:1577	N-glycan synthesis	1560:1577	N-glycan synthesis in the rat neocortex	1560:1598	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
33242084	4	66	theme	ultraperformance	737:752	arg1	chromatography					761:774	hydrophilic interaction ultraperformance liquid chromatography	713:774	hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry	713:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	5	67	theme	N-glycans	974:982	arg1	abundance					953:961	the abundance	949:961	the abundance of complex N-glycans	949:982	We report that the abundance of complex N-glycans is significantly lower in adults compared with neonates.
33242084	5	67	theme	N-glycans	974:982	arg1	lower					1001:1005	lower	1001:1005	lower	1001:1005	We report that the abundance of complex N-glycans is significantly lower in adults compared with neonates.
33242084	1	68	theme	key	144:146	arg1	role					148:151	a key role	142:151	a key role	142:151	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	0	69	theme	neocortical	63:73	arg1	N-glycome					75:83	the rat neocortical N-glycome	55:83	the rat neocortical N-glycome	55:83	Post-natal developmental changes in the composition of the rat neocortical N-glycome.
33242084	1	70	theme	neurite	223:229	arg1	outgrowth					231:239	neurite outgrowth	223:239	neurite outgrowth	223:239	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	4	71	theme	electrospray	787:798	arg1	spectrometry					842:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	electrospray ionization quadrupole time-of-flight mass spectrometry	787:853	To this end, we used hydrophilic interaction ultraperformance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry to compare the adult neocortical N-glycome with that of 24- and 48-h neonates.
33242084	3	72	dep	neocortex	578:586	arg1	both					546:549	both	546:549	both	546:549	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	3	73	theme	study	463:467	arg1	aim					451:453	The aim	447:453	The aim of this study	447:467	The aim of this study, therefore, was to perform a thorough characterization of N-glycosylation in both the adult and neonatal rat neocortex in order to gain insights into the types of changes occurring in the N-glycome during neurodevelopment.
33242084	1	74	theme	axon	245:248	arg1	targeting					250:258	axon targeting	245:258	axon targeting	245:258	Asparagine-linked glycosylation (N-glycosylation) plays a key role in many neurodevelopmental processes, including neural cell adhesion, neurite outgrowth and axon targeting.
33242084	0	75	theme	rat	59:61	arg1	N-glycome					75:83	the rat neocortical N-glycome	55:83	the rat neocortical N-glycome	55:83	Post-natal developmental changes in the composition of the rat neocortical N-glycome.
33242084	8	76	theme	smaller	1490:1496	arg1	subtypes					1498:1505	smaller subtypes	1490:1505	smaller subtypes in the adult	1490:1518	Lastly, we report that although the proportion of oligomannose N-glycans remains constant at around 24%, the distribution of high-mannose subtypes shifts from predominantly large subtypes in neonates to smaller subtypes in the adult.
33242084	9	77	with	adults	1653:1658	arg1	shift					1675:1679	a general shift	1665:1679	a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures	1665:1861	In summary, our findings indicate that N-glycan synthesis in the rat neocortex is fundamentally different in neonates compared with adults with a general shift occurring from large, sialylated N-glycans towards smaller, neutral structures as neonates develop into adults, coupled with a parallel shift towards smaller oligomannose structures.
31777161	6	0	theme	xylosyltransferase	740:757	arg1	candidate					759:767	another xylosyltransferase candidate	732:767	another xylosyltransferase candidate named XTB	732:777	Furthermore, another xylosyltransferase candidate named XTB was suggested to be involved in the xylosylation in C. reinhardtii.
31777161	8	1	theme	spectrometry	1094:1105	arg1	approaches					1107:1116	mass spectrometry approaches	1089:1116	mass spectrometry approaches	1089:1116	The combination of mass spectrometry approaches allowed us to identify the major N-glycan structures bearing one or two xylose residues.
31777161	12	2	theme	N-glycosylation	1827:1841	arg1	pathway					1843:1849	the C. reinhardtii N-glycosylation pathway	1808:1849	the C. reinhardtii N-glycosylation pathway	1808:1849	Altogether, these results pave the way for a better understanding of the C. reinhardtii N-glycosylation pathway.
31777161	11	3	theme	C. reinhardtii	1716:1729	arg1	genome					1731:1736	the C. reinhardtii genome	1712:1736	the C. reinhardtii genome	1712:1736	Additional putative candidates have been identified in the C. reinhardtii genome.
31777161	5	4	theme	-xylose	710:716	arg1	addition					683:690	the addition	679:690	the addition of the core β(1,2)-xylose	679:716	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	12	5	theme	better	1784:1789	arg1	understanding					1791:1803	a better understanding	1782:1803	a better understanding of the C. reinhardtii N-glycosylation pathway	1782:1849	Altogether, these results pave the way for a better understanding of the C. reinhardtii N-glycosylation pathway.
31777161	1	6	theme	green	198:202	arg1	reinhardtii					228:238	the green microalga Chlamydomonas reinhardtii	194:238	the green microalga Chlamydomonas reinhardtii	194:238	Nowadays, little information is available regarding the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii.
31777161	9	7	theme	core	1268:1271	arg1	-xylose					1279:1285	the core β(1,2)-xylose	1264:1285	the core β(1,2)-xylose	1264:1285	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	11	8	theme	Additional	1657:1666	arg1	candidates					1677:1686	Additional putative candidates	1657:1686	Additional putative candidates	1657:1686	Additional putative candidates have been identified in the C. reinhardtii genome.
31777161	7	9	theme	xylosylated	938:948	arg1	N-glycans					950:958	the xylosylated N-glycans	934:958	the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	934:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	10	10	theme	additional	1568:1577	arg1	xylosyltransferase					1579:1596	an additional xylosyltransferase	1565:1596	an additional xylosyltransferase	1565:1596	Analysis of the double-mutant suggests that an additional xylosyltransferase is involved in the xylosylation process in C. reinhardtii.
31777161	10	11	from	process	1630:1636	arg1	C. reinhardtii					1641:1654	C. reinhardtii	1641:1654	C. reinhardtii	1641:1654	Analysis of the double-mutant suggests that an additional xylosyltransferase is involved in the xylosylation process in C. reinhardtii.
31777161	8	12	theme	approaches	1107:1116	arg1	combination					1074:1084	The combination	1070:1084	The combination of mass spectrometry approaches	1070:1116	The combination of mass spectrometry approaches allowed us to identify the major N-glycan structures bearing one or two xylose residues.
31777161	1	13	from	pathway	183:189	arg1	reinhardtii					228:238	the green microalga Chlamydomonas reinhardtii	194:238	the green microalga Chlamydomonas reinhardtii	194:238	Nowadays, little information is available regarding the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii.
31777161	7	14	theme	structures	920:929	arg1	characterization					896:911	the characterization	892:911	the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	892:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	9	15	theme	core	1431:1434	arg1	-xylose					1442:1448	the core β(1,2)-xylose	1427:1448	the core β(1,2)-xylose	1427:1448	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	9	16	theme	xylose	1335:1340	arg1	residue					1342:1348	the xylose residue	1331:1348	the xylose residue onto the linear branch of the N-glycan	1331:1387	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	5	17	theme	core	699:702	arg1	-xylose					710:716	the core β(1,2)-xylose	695:716	the core β(1,2)-xylose	695:716	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	1	18	theme	microalga	204:212	arg1	reinhardtii					228:238	the green microalga Chlamydomonas reinhardtii	194:238	the green microalga Chlamydomonas reinhardtii	194:238	Nowadays, little information is available regarding the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii.
31777161	3	19	theme	xylose	439:444	arg1	residues					446:453	one or two xylose residues	428:453	one or two xylose residues	428:453	Maturation of these oligomannosides results in N-glycans that are partially methylated and carry one or two xylose residues.
31777161	9	20	theme	residue	1342:1348	arg1	addition					1319:1326	the addition	1315:1326	the addition of the xylose residue onto the linear branch of the N-glycan	1315:1387	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	5	21	theme	β	704:704	arg1	-xylose					710:716	the core β(1,2)-xylose	695:716	the core β(1,2)-xylose	695:716	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	4	22	theme	xylose	460:465	arg1	residue					467:473	One xylose residue	456:473	One xylose residue	456:473	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	4	22	theme	xylose	460:465	arg1	-xylose					511:517	a core β(1,2)-xylose	498:517	a core β(1,2)-xylose	498:517	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	1	23	theme	Nowadays	111:118	arg1	information					128:138	Nowadays, little information	111:138	information	128:138	Nowadays, little information is available regarding the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii.
31777161	1	24	theme	Chlamydomonas	214:226	arg1	reinhardtii					228:238	the green microalga Chlamydomonas reinhardtii	194:238	the green microalga Chlamydomonas reinhardtii	194:238	Nowadays, little information is available regarding the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii.
31777161	7	25	theme	XTA	1023:1025	arg1	mutants					1012:1018	insertional mutants	1000:1018	insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	1000:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	7	26	from	C. reinhardtii	965:978	arg1	N-glycans					950:958	the xylosylated N-glycans	934:958	the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	934:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	7	26	from	C. reinhardtii	965:978	arg1	structures					920:929	the structures	916:929	the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	916:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	9	27	theme	1,2	1438:1440	arg1	-xylose					1442:1448	the core β(1,2)-xylose	1427:1448	the core β(1,2)-xylose	1427:1448	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	0	28	theme	Multiple	0:7	arg1	xylosyltransferases					9:27	Multiple xylosyltransferases	0:27	Multiple xylosyltransferases	0:27	Multiple xylosyltransferases heterogeneously xylosylate protein N-linked glycans in Chlamydomonas reinhardtii.
31777161	10	29	theme	xylosylation	1617:1628	arg1	process					1630:1636	the xylosylation process	1613:1636	the xylosylation process in C. reinhardtii	1613:1654	Analysis of the double-mutant suggests that an additional xylosyltransferase is involved in the xylosylation process in C. reinhardtii.
31777161	5	30	theme	1,2	706:708	arg1	-xylose					710:716	the core β(1,2)-xylose	695:716	the core β(1,2)-xylose	695:716	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	0	31	link	N-linked	64:71	arg1	glycans					73:79	protein N-linked glycans	56:79	protein N-linked glycans	56:79	Multiple xylosyltransferases heterogeneously xylosylate protein N-linked glycans in Chlamydomonas reinhardtii.
31777161	1	32	theme	little	121:126	arg1	information					128:138	Nowadays, little information	111:138	information	128:138	Nowadays, little information is available regarding the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii.
31777161	8	33	theme	mass	1089:1092	arg1	approaches					1107:1116	mass spectrometry approaches	1089:1116	mass spectrometry approaches	1089:1116	The combination of mass spectrometry approaches allowed us to identify the major N-glycan structures bearing one or two xylose residues.
31777161	7	34	theme	insertional	1000:1010	arg1	mutants					1012:1018	insertional mutants	1000:1018	insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	1000:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	8	35	theme	N-glycan	1151:1158	arg1	structures					1160:1169	the major N-glycan structures	1141:1169	the major N-glycan structures bearing one or two xylose residues	1141:1204	The combination of mass spectrometry approaches allowed us to identify the major N-glycan structures bearing one or two xylose residues.
31777161	7	36	theme	mutants	1012:1018	arg1	advantage					987:995	advantage	987:995	advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	987:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	5	37	theme	N-glycoproteomic	530:545	arg1	analysis					547:554	N-glycoproteomic analysis	530:554	N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii	530:608	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	9	38	theme	-xylose	1442:1448	arg1	addition					1415:1422	the partial addition	1403:1422	the partial addition of the core β(1,2)-xylose	1403:1448	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	9	39	theme	β	1273:1273	arg1	-xylose					1279:1285	the core β(1,2)-xylose	1264:1285	the core β(1,2)-xylose	1264:1285	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	8	40	theme	major	1145:1149	arg1	structures					1160:1169	the major N-glycan structures	1141:1169	the major N-glycan structures bearing one or two xylose residues	1141:1204	The combination of mass spectrometry approaches allowed us to identify the major N-glycan structures bearing one or two xylose residues.
31777161	9	41	theme	1,2	1275:1277	arg1	-xylose					1279:1285	the core β(1,2)-xylose	1264:1285	the core β(1,2)-xylose	1264:1285	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	0	42	theme	N-linked	64:71	arg1	glycans					73:79	protein N-linked glycans	56:79	protein N-linked glycans	56:79	Multiple xylosyltransferases heterogeneously xylosylate protein N-linked glycans in Chlamydomonas reinhardtii.
31777161	3	43	theme	oligomannosides	351:365	arg1	Maturation					331:340	Maturation	331:340	Maturation of these oligomannosides	331:365	Maturation of these oligomannosides results in N-glycans that are partially methylated and carry one or two xylose residues.
31777161	0	44	theme	protein	56:62	arg1	glycans					73:79	protein N-linked glycans	56:79	protein N-linked glycans	56:79	Multiple xylosyltransferases heterogeneously xylosylate protein N-linked glycans in Chlamydomonas reinhardtii.
31777161	9	45	theme	-xylose	1279:1285	arg1	addition					1252:1259	the addition	1248:1259	the addition of the core β(1,2)-xylose	1248:1285	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	2	46	theme	linear	307:312	arg1	oligomannosides					314:328	linear oligomannosides	307:328	linear oligomannosides	307:328	Recent investigation demonstrated that C. reinhardtii synthesizes linear oligomannosides.
31777161	5	47	theme	xylosyltransferase	632:649	arg1	responsible					663:673	responsible	663:673	responsible	663:673	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	5	47	theme	xylosyltransferase	632:649	arg1	A					651:651	the xylosyltransferase A	628:651	the xylosyltransferase A (XTA)	628:657	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	5	47	theme	xylosyltransferase	632:649	arg1	XTA					654:656	XTA	654:656	XTA	654:656	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	7	48	theme	present	854:860	arg1	study					862:866	the present study	850:866	the present study	850:866	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	9	49	theme	linear	1359:1364	arg1	branch					1366:1371	the linear branch	1355:1371	the linear branch of the N-glycan	1355:1387	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	9	50	theme	β	1436:1436	arg1	-xylose					1442:1448	the core β(1,2)-xylose	1427:1448	the core β(1,2)-xylose	1427:1448	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	6	51	from	xylosylation	815:826	arg1	C. reinhardtii					831:844	C. reinhardtii	831:844	C. reinhardtii	831:844	Furthermore, another xylosyltransferase candidate named XTB was suggested to be involved in the xylosylation in C. reinhardtii.
31777161	9	52	theme	low	1494:1496	arg1	specificity					1508:1518	a low substrate specificity	1492:1518	a low substrate specificity	1492:1518	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	11	53	theme	putative	1668:1675	arg1	candidates					1677:1686	Additional putative candidates	1657:1686	Additional putative candidates	1657:1686	Additional putative candidates have been identified in the C. reinhardtii genome.
31777161	4	54	theme	β	505:505	arg1	residue					467:473	One xylose residue	456:473	One xylose residue	456:473	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	4	54	theme	β	505:505	arg1	-xylose					511:517	a core β(1,2)-xylose	498:517	a core β(1,2)-xylose	498:517	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	8	55	theme	xylose	1190:1195	arg1	residues					1197:1204	one or two xylose residues	1179:1204	one or two xylose residues	1179:1204	The combination of mass spectrometry approaches allowed us to identify the major N-glycan structures bearing one or two xylose residues.
31777161	4	56	theme	core	500:503	arg1	residue					467:473	One xylose residue	456:473	One xylose residue	456:473	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	4	56	theme	core	500:503	arg1	-xylose					511:517	a core β(1,2)-xylose	498:517	a core β(1,2)-xylose	498:517	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	9	57	dep	responsible	1232:1242	arg1	whereas					1288:1294	whereas	1288:1294	whereas	1288:1294	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	4	58	theme	1,2	507:509	arg1	residue					467:473	One xylose residue	456:473	One xylose residue	456:473	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	4	58	theme	1,2	507:509	arg1	-xylose					511:517	a core β(1,2)-xylose	498:517	a core β(1,2)-xylose	498:517	One xylose residue was demonstrated to be a core β(1,2)-xylose.
31777161	3	59	contain	carry	422:426	arg1	N-glycans					378:386	N-glycans	378:386	N-glycans that are partially methylated and carry one or two xylose residues	378:453	Maturation of these oligomannosides results in N-glycans that are partially methylated and carry one or two xylose residues.
31777161	3	59	contain	carry	422:426	arg2	residues					446:453	one or two xylose residues	428:453	one or two xylose residues	428:453	Maturation of these oligomannosides results in N-glycans that are partially methylated and carry one or two xylose residues.
31777161	1	60	theme	N-glycosylation	167:181	arg1	pathway					183:189	the N-glycosylation pathway	163:189	the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii	163:238	Nowadays, little information is available regarding the N-glycosylation pathway in the green microalga Chlamydomonas reinhardtii.
31777161	12	61	theme	C. reinhardtii	1812:1825	arg1	pathway					1843:1849	the C. reinhardtii N-glycosylation pathway	1808:1849	the C. reinhardtii N-glycosylation pathway	1808:1849	Altogether, these results pave the way for a better understanding of the C. reinhardtii N-glycosylation pathway.
31777161	2	62	theme	Recent	241:246	arg1	investigation					248:260	Recent investigation	241:260	Recent investigation	241:260	Recent investigation demonstrated that C. reinhardtii synthesizes linear oligomannosides.
31777161	7	63	from	structures	920:929	arg1	C. reinhardtii					965:978	C. reinhardtii	965:978	C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	965:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	7	64	theme	double-mutant	1055:1067	arg1	mutants					1012:1018	insertional mutants	1000:1018	insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	1000:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	9	65	theme	substrate	1498:1506	arg1	specificity					1508:1518	a low substrate specificity	1492:1518	a low substrate specificity	1492:1518	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	10	66	theme	double-mutant	1537:1549	arg1	Analysis					1521:1528	Analysis	1521:1528	Analysis of the double-mutant	1521:1549	Analysis of the double-mutant suggests that an additional xylosyltransferase is involved in the xylosylation process in C. reinhardtii.
31777161	5	67	gly	glycoproteins	569:581	arg1	glycoproteins					569:581	glycoproteins	569:581	glycoproteins secreted by C. reinhardtii	569:608	Recently, N-glycoproteomic analysis performed on glycoproteins secreted by C. reinhardtii demonstrated that the xylosyltransferase A (XTA) was responsible for the addition of the core β(1,2)-xylose.
31777161	9	68	theme	partial	1407:1413	arg1	addition					1415:1422	the partial addition	1403:1422	the partial addition of the core β(1,2)-xylose	1403:1448	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
31777161	12	69	theme	pathway	1843:1849	arg1	understanding					1791:1803	a better understanding	1782:1803	a better understanding of the C. reinhardtii N-glycosylation pathway	1782:1849	Altogether, these results pave the way for a better understanding of the C. reinhardtii N-glycosylation pathway.
31777161	7	70	theme	N-glycans	950:958	arg1	structures					920:929	the structures	916:929	the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant	916:1067	In the present study, we focus especially on the characterization of the structures of the xylosylated N-glycans from C. reinhardtii taking advantage of insertional mutants of XTA and XTB, and of the XTA/XTB double-mutant.
31777161	9	71	theme	N-glycan	1380:1387	arg1	branch					1366:1371	the linear branch	1355:1371	the linear branch of the N-glycan	1355:1387	They confirm that XTA is responsible for the addition of the core β(1,2)-xylose, whereas XTB is involved in the addition of the xylose residue onto the linear branch of the N-glycan as well as in the partial addition of the core β(1,2)-xylose suggesting that this transferase exhibits a low substrate specificity.
34341430	8	0	theme	serum	1487:1491	arg1	concentrations					1497:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	6	1	theme	seminal	1164:1170	arg1	plasma					1172:1177	seminal plasma	1164:1177	seminal plasma	1164:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	3	2	dep	fucose	614:619	arg1	UEA					627:629	UEA	627:629	UEA	627:629	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	3	2	dep	fucose	614:619	arg1	LCA					636:638	LCA	636:638	LCA	636:638	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	3	2	dep	fucose	614:619	arg1	LTA					622:624	LTA	622:624	LTA	622:624	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	7	3	theme	OAT	1367:1369	arg1	group					1371:1375	the OAT group	1363:1375	the OAT group	1363:1375	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	3	4	link	α1,6-linked	597:607	arg1	fucose					614:619	α1,6-linked core fucose	597:619	α1,6-linked core fucose (LTA, UEA, and LCA, respectively)	597:653	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	7	5	theme	plasma	1328:1333	arg1	CLU					1335:1337	seminal plasma CLU	1320:1337	seminal plasma CLU	1320:1337	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	6	6	from	parameters	1134:1143	arg1	serum					1154:1158	blood serum	1148:1158	blood serum	1148:1158	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	6	6	from	parameters	1134:1143	arg1	plasma					1172:1177	seminal plasma	1164:1177	seminal plasma	1164:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	3	7	theme	CLU	468:470	arg1	fucosylation					472:483	The CLU fucosylation	464:483	The CLU fucosylation	464:483	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	4	8	theme	ELISA	773:777	arg1	tests					779:783	ELISA tests	773:783	ELISA tests	773:783	The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests.
34341430	6	9	theme	examined	1125:1132	arg1	parameters					1134:1143	examined parameters	1125:1143	examined parameters in blood serum and seminal plasma	1125:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	2	10	theme	infertile	260:268	arg1	men					270:272	infertile men	260:272	infertile men	260:272	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	1	11	theme	fucosylation	161:172	arg1	FUTs					226:229	the fucosylation and the expression of selected fucosyltransferases (FUTs)	157:230	the fucosylation and the expression of selected fucosyltransferases (FUTs)	157:230	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	7	12	theme	observed	1278:1285	arg1	differences					1287:1297	the observed differences	1274:1297	the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups	1274:1395	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	3	13	link	α1,2-linked	563:573	arg1	fucose					585:590	α1,2-linked antennary fucose	563:590	α1,2-linked antennary fucose	563:590	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	8	14	theme	normozoospermic	1613:1627	arg1	men					1629:1631	normozoospermic men	1613:1631	normozoospermic men	1613:1631	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	5	15	theme	other	949:953	arg1	groups					955:960	other groups	949:960	other groups examined	949:969	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	3	16	theme	antennary	575:583	arg1	fucose					585:590	α1,2-linked antennary fucose	563:590	α1,2-linked antennary fucose	563:590	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	2	17	theme	oligoasthenoteratozoospermic	428:455	arg1	groups					292:297	groups	292:297	groups based on the results of the standard semen analysis	292:349	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	8	18	attach	α1,2-linked	1553:1563	arg3	CLU					1568:1570	CLU	1568:1570	CLU	1568:1570	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	6	19	from	levels	1115:1120	arg1	serum					1154:1158	blood serum	1148:1158	blood serum	1148:1158	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	6	19	from	levels	1115:1120	arg1	plasma					1172:1177	seminal plasma	1164:1177	seminal plasma	1164:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	0	20	theme	male	64:67	arg1	disorders					79:87	male fertility disorders	64:87	male fertility disorders	64:87	The possible association of clusterin fucosylation changes with male fertility disorders.
34341430	8	21	theme	sperm	1658:1662	arg1	parameters					1664:1673	abnormal sperm parameters	1649:1673	abnormal sperm parameters	1649:1673	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	5	22	theme	serum	805:809	arg1	CLU					811:813	serum CLU and FUT4 concentrations	805:837	CLU	811:813	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	2	23	from	men	270:272	arg1	Samples					247:253	Samples	247:253	Samples from infertile men	247:272	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	2	24	dep	asthenoteratozoospermic	395:417	arg1	AT					420:421	AT	420:421	AT	420:421	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	5	25	theme	fucose	870:875	arg1	expression					851:860	the expression	847:860	the expression of core fucose and antennary fucose α1,2-linked in CLU glycans	847:923	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	7	26	theme	decreased	1414:1422	arg1	count					1430:1434	decreased sperm count	1414:1434	decreased sperm count	1414:1434	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	6	27	theme	glycoproteins	1232:1244	arg1	glycosylation					1246:1258	glycoproteins glycosylation	1232:1258	glycoproteins glycosylation	1232:1258	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	5	28	theme	sperm	1004:1008	arg1	count					1010:1014	sperm count	1004:1014	sperm count	1004:1014	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	5	29	theme	antennary	881:889	arg1	fucose					891:896	antennary fucose	881:896	antennary fucose	881:896	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	2	30	dep	groups	292:297	arg1	N					369:369	N	369:369	N	369:369	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	2	30	dep	groups	292:297	arg1	normozoospermic					352:366	normozoospermic	352:366	normozoospermic	352:366	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	2	31	theme	semen	336:340	arg1	analysis					342:349	the standard semen analysis	323:349	the standard semen analysis	323:349	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	5	32	theme	only	1054:1057	arg1	cause					1059:1063	the only cause	1050:1063	the only cause of male infertility	1050:1083	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	5	32	theme	only	1054:1057	arg1	disturbances					988:999	the disturbances	984:999	the disturbances in sperm count, motility, and morphology	984:1040	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	8	33	theme	seminal	1703:1709	arg1	plasma					1711:1716	seminal plasma	1703:1716	seminal plasma	1703:1716	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	6	34	theme	blood	1148:1152	arg1	serum					1154:1158	blood serum	1148:1158	blood serum	1148:1158	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	2	35	theme	teratozoospermic	373:388	arg1	groups					292:297	groups	292:297	groups based on the results of the standard semen analysis	292:349	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	3	36	theme	α1,6-linked	597:607	arg1	fucose					614:619	α1,6-linked core fucose	597:619	α1,6-linked core fucose (LTA, UEA, and LCA, respectively)	597:653	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	4	37	theme	oligosaccharide	725:739	arg1	structures					741:750	Le oligosaccharide structures	722:750	Le oligosaccharide structures	722:750	The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests.
34341430	0	38	theme	clusterin	28:36	arg1	fucosylation					38:49	clusterin fucosylation	28:49	clusterin fucosylation	28:49	The possible association of clusterin fucosylation changes with male fertility disorders.
34341430	7	39	theme	AT	1387:1388	arg1	groups					1390:1395	AT groups	1387:1395	AT groups	1387:1395	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	7	39	theme	AT	1387:1388	arg1	N					1381:1381	N	1381:1381	N	1381:1381	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	6	40	from	differences	1195:1205	arg1	mechanisms					1210:1219	mechanisms	1210:1219	mechanisms leading to glycoproteins glycosylation	1210:1258	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	5	41	theme	N	937:937	arg1	group					939:943	the N group	933:943	the N group	933:943	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	1	42	theme	expression	182:191	arg1	FUTs					226:229	the fucosylation and the expression of selected fucosyltransferases (FUTs)	157:230	the fucosylation and the expression of selected fucosyltransferases (FUTs)	157:230	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	5	43	theme	α1,2-linked	898:908	arg1	glycans					917:923	α1,2-linked in CLU glycans	898:923	α1,2-linked in CLU glycans	898:923	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	6	44	from	plasma	1172:1177	arg1	levels					1115:1120	levels	1115:1120	levels of examined parameters in blood serum and seminal plasma	1115:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	8	45	theme	fucose	1535:1540	arg1	expression					1516:1525	expression	1516:1525	expression of core fucose and fucose	1516:1551	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	8	45	theme	fucose	1535:1540	arg1	concentrations					1497:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	5	46	theme	infertility	1073:1083	arg1	cause					1059:1063	the only cause	1050:1063	the only cause of male infertility	1050:1083	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	5	46	theme	infertility	1073:1083	arg1	disturbances					988:999	the disturbances	984:999	the disturbances in sperm count, motility, and morphology	984:1040	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	8	47	theme	fucose	1546:1551	arg1	expression					1516:1525	expression	1516:1525	expression of core fucose and fucose	1516:1551	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	8	47	theme	fucose	1546:1551	arg1	concentrations					1497:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	7	48	theme	FUT4	1350:1353	arg1	concentrations					1302:1315	concentrations	1302:1315	concentrations of seminal plasma CLU, FUT3, and FUT4	1302:1353	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	7	49	theme	FUT3	1340:1343	arg1	concentrations					1302:1315	concentrations	1302:1315	concentrations of seminal plasma CLU, FUT3, and FUT4	1302:1353	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	8	50	theme	CLU	1493:1495	arg1	concentrations					1497:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations	1483:1510	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	1	51	gly	fucosylation	161:172	arg1	fucosyltransferases					205:223	selected fucosyltransferases	196:223	selected fucosyltransferases	196:223	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	5	52	from	CLU	913:915	arg1	α1,2-linked					898:908	α1,2-linked	898:908	α1,2-linked	898:908	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	7	53	theme	sperm	1424:1428	arg1	count					1430:1434	decreased sperm count	1414:1434	decreased sperm count	1414:1434	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	7	54	theme	CLU	1335:1337	arg1	concentrations					1302:1315	concentrations	1302:1315	concentrations of seminal plasma CLU, FUT3, and FUT4	1302:1353	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	6	55	theme	parameters	1134:1143	arg1	levels					1115:1120	levels	1115:1120	levels of examined parameters in blood serum and seminal plasma	1115:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	5	56	from	α1,2-linked	898:908	arg1	CLU					913:915	CLU	913:915	CLU	913:915	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	7	57	theme	seminal	1320:1326	arg1	CLU					1335:1337	seminal plasma CLU	1320:1337	seminal plasma CLU	1320:1337	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	5	58	link	α1,2-linked	898:908	arg1	glycans					917:923	α1,2-linked in CLU glycans	898:923	α1,2-linked in CLU glycans	898:923	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	3	59	theme	specific	544:551	arg1	lectins					536:542	biotinylated lectins	523:542	biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively)	523:653	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	8	60	theme	good	1584:1587	arg1	markers					1589:1595	good markers	1584:1595	good markers	1584:1595	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	8	61	dep	α1,2-linked	1553:1563	arg1	seem					1573:1576	seem	1573:1576	seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma	1573:1716	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	3	62	theme	biotinylated	523:534	arg1	lectins					536:542	biotinylated lectins	523:542	biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively)	523:653	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	5	63	theme	FUT4	819:822	arg1	concentrations					824:837	serum CLU and FUT4 concentrations	805:837	concentrations	824:837	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	6	64	theme	similarities	1094:1105	arg1	Lack					1086:1089	Lack	1086:1089	Lack of similarities between levels of examined parameters in blood serum and seminal plasma	1086:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	3	65	theme	α1,2-linked	563:573	arg1	fucose					585:590	α1,2-linked antennary fucose	563:590	α1,2-linked antennary fucose	563:590	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	5	66	dep	fucose	870:875	arg1	glycans					917:923	α1,2-linked in CLU glycans	898:923	α1,2-linked in CLU glycans	898:923	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	0	67	theme	fertility	69:77	arg1	disorders					79:87	male fertility disorders	64:87	male fertility disorders	64:87	The possible association of clusterin fucosylation changes with male fertility disorders.
34341430	5	68	from	differences	790:800	arg1	CLU					811:813	serum CLU and FUT4 concentrations	805:837	CLU	811:813	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	5	68	from	differences	790:800	arg1	expression					851:860	the expression	847:860	the expression of core fucose and antennary fucose α1,2-linked in CLU glycans	847:923	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	1	69	theme	serum	126:130	arg1	CLU					152:154	CLU	152:154	CLU	152:154	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	1	69	theme	serum	126:130	arg1	clusterin					141:149	serum (n = 90) clusterin	126:149	serum (n = 90) clusterin (CLU)	126:155	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	8	70	theme	abnormal	1649:1656	arg1	parameters					1664:1673	abnormal sperm parameters	1649:1673	abnormal sperm parameters	1649:1673	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	5	71	attach	α1,2-linked	898:908	arg3	CLU					913:915	CLU	913:915	CLU	913:915	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	5	72	theme	core	865:868	arg1	fucose					870:875	core fucose	865:875	core fucose	865:875	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	4	73	theme	FUT3	678:681	arg1	concentrations					660:673	The concentrations	656:673	The concentrations	656:673	The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests.
34341430	7	74	dep	parameters	1460:1469	arg1	expression					1471:1480	expression	1471:1480	these parameters expression	1454:1480	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	2	75	dep	teratozoospermic	373:388	arg1	T					391:391	T	391:391	T	391:391	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	4	76	theme	FUT4	687:690	arg1	concentrations					660:673	The concentrations	656:673	The concentrations	656:673	The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests.
34341430	2	77	theme	analysis	342:349	arg1	results					312:318	the results	308:318	the results of the standard semen analysis	308:349	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	0	78	theme	possible	4:11	arg1	association					13:23	The possible association	0:23	The possible association of clusterin fucosylation	0:49	The possible association of clusterin fucosylation changes with male fertility disorders.
34341430	1	79	theme	selected	196:203	arg1	fucosyltransferases					205:223	selected fucosyltransferases	196:223	selected fucosyltransferases	196:223	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	2	80	theme	standard	327:334	arg1	analysis					342:349	the standard semen analysis	323:349	the standard semen analysis	323:349	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	3	81	with	lectin-ELISAs	504:516	arg1	lectins					536:542	biotinylated lectins	523:542	biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively)	523:653	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	1	82	theme	seminal	97:103	arg1	n = 118					113:119	n = 118	113:119	n = 118	113:119	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	1	82	theme	seminal	97:103	arg1	plasma					105:110	the seminal plasma	93:110	the seminal plasma (n = 118)	93:120	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	0	83	theme	fucosylation	38:49	arg1	association					13:23	The possible association	0:23	The possible association of clusterin fucosylation	0:49	The possible association of clusterin fucosylation changes with male fertility disorders.
34341430	5	84	theme	male	1068:1071	arg1	infertility					1073:1083	male infertility	1068:1083	male infertility	1068:1083	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	7	85	from	differences	1287:1297	arg1	concentrations					1302:1315	concentrations	1302:1315	concentrations of seminal plasma CLU, FUT3, and FUT4	1302:1353	It confirmed the observed differences in concentrations of seminal plasma CLU, FUT3, and FUT4 between the OAT group and N, T, AT groups, indicating that decreased sperm count may be related to these parameters expression.
34341430	2	86	theme	asthenoteratozoospermic	395:417	arg1	groups					292:297	groups	292:297	groups based on the results of the standard semen analysis	292:349	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	4	87	theme	Le	722:723	arg1	structures					741:750	Le oligosaccharide structures	722:750	Le oligosaccharide structures	722:750	The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests.
34341430	6	88	gly	glycoproteins	1232:1244	arg1	glycoproteins					1232:1244	glycoproteins glycosylation	1232:1258	glycoproteins glycosylation	1232:1258	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	4	89	theme	structures	741:750	arg1	expression					708:717	the expression	704:717	the expression of Le oligosaccharide structures	704:750	The concentrations of FUT3 and FUT4, reflecting the expression of Le oligosaccharide structures, were measured using ELISA tests.
34341430	2	90	dep	oligoasthenoteratozoospermic	428:455	arg1	OAT					458:460	OAT	458:460	OAT	458:460	Samples from infertile men were divided into groups based on the results of the standard semen analysis: normozoospermic (N), teratozoospermic (T), asthenoteratozoospermic (AT) and oligoasthenoteratozoospermic (OAT).
34341430	5	91	theme	fucose	891:896	arg1	expression					851:860	the expression	847:860	the expression of core fucose and antennary fucose α1,2-linked in CLU glycans	847:923	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	3	92	theme	core	609:612	arg1	fucose					614:619	α1,6-linked core fucose	597:619	α1,6-linked core fucose (LTA, UEA, and LCA, respectively)	597:653	The CLU fucosylation was analyzed using lectin-ELISAs with biotinylated lectins specific to α1,3-, α1,2-linked antennary fucose, and α1,6-linked core fucose (LTA, UEA, and LCA, respectively).
34341430	8	93	theme	core	1530:1533	arg1	fucose					1535:1540	core fucose	1530:1540	core fucose	1530:1540	The serum CLU concentrations and expression of core fucose and fucose α1,2-linked in CLU, seem to be good markers differentiating normozoospermic men from those with abnormal sperm parameters, which was not observed for seminal plasma.
34341430	6	94	from	serum	1154:1158	arg1	levels					1115:1120	levels	1115:1120	levels of examined parameters in blood serum and seminal plasma	1115:1177	Lack of similarities between levels of examined parameters in blood serum and seminal plasma may suggest the differences in mechanisms leading to glycoproteins glycosylation.
34341430	5	95	from	disturbances	988:999	arg1	motility					1017:1024	motility	1017:1024	motility	1017:1024	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	5	95	from	disturbances	988:999	arg1	morphology					1031:1040	morphology	1031:1040	morphology	1031:1040	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	5	95	from	disturbances	988:999	arg1	count					1010:1014	sperm count	1004:1014	sperm count	1004:1014	The differences in serum CLU and FUT4 concentrations, and in the expression of core fucose and antennary fucose α1,2-linked in CLU glycans between the N group and other groups examined suggest that the disturbances in sperm count, motility, and morphology are not the only cause of male infertility.
34341430	1	96	theme	fucosyltransferases	205:223	arg1	fucosylation					161:172	fucosylation	161:172	fucosylation	161:172	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
34341430	1	96	theme	fucosyltransferases	205:223	arg1	expression					182:191	the expression	178:191	the expression of selected fucosyltransferases	178:223	In the seminal plasma (n = 118) and serum (n = 90) clusterin (CLU) the fucosylation and the expression of selected fucosyltransferases (FUTs) were analyzed.
33107910	7	0	theme	glycosylated	1143:1154	arg1	Fabs					1156:1159	glycosylated Fabs	1143:1159	glycosylated Fabs in the rats	1143:1171	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	4	1	theme	Expressed	542:550	arg1	Fab					559:561	Expressed mutant Fab	542:561	Expressed mutant Fab	542:561	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	0	2	theme	Pichia	87:92	arg1	pastoris					94:101	Pichia pastoris	87:101	Pichia pastoris	87:101	Glycosylation decreases aggregation and immunogenicity of adalimumab Fab secreted from Pichia pastoris.
33107910	7	3	theme	behaviour	1060:1068	arg1	Analysis					1028:1035	Analysis	1028:1035	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab	1028:1108	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	4	from	rats	1168:1171	arg1	half-lives					1129:1138	the half-lives	1125:1138	the half-lives of glycosylated Fabs in the rats	1125:1171	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	4	from	rats	1168:1171	arg1	shorter					1178:1184	shorter	1178:1184	shorter	1178:1184	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	1	5	theme	clinical	177:184	arg1	efficacy					186:193	the clinical efficacy	173:193	the clinical efficacy of several therapeutics	173:217	Glycoengineering of therapeutic proteins has been applied to improve the clinical efficacy of several therapeutics.
33107910	5	6	theme	aggregation	670:680	arg1	condition					657:665	the condition	653:665	the condition of aggregation of Fab upon pH shift-induced stress	653:716	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	7	7	theme	shorter	1240:1246	arg1	half-life					1248:1256	a shorter half-life	1238:1256	a shorter half-life than S-glyco Fab	1238:1273	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	8	theme	pharmacokinetic	1044:1058	arg1	behaviour					1060:1068	the pharmacokinetic behaviour	1040:1068	the pharmacokinetic behaviour of the Fab	1040:1079	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	5	9	theme	L-glyco	727:733	arg1	Fab					735:737	L-glyco Fab	727:737	L-glyco Fab	727:737	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	7	10	gly	glycosylated	1143:1154	arg1	Fabs					1156:1159	glycosylated Fabs	1143:1159	glycosylated Fabs in the rats	1143:1171	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	6	11	theme	glycosylated	915:926	arg1	Fabs					942:945	glycosylated and wild-type Fabs	915:945	glycosylated and wild-type Fabs	915:945	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	3	12	dep	L178N	477:481	arg1	Fab					483:485	Fab	483:485	L178N Fab	477:485	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	7	13	theme	L-glyco	1082:1088	arg1	Fab					1090:1092	L-glyco Fab	1082:1092	L-glyco Fab	1082:1092	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	2	14	theme	Fab	291:293	arg1	properties					273:282	the properties	269:282	the properties of the Fab of the therapeutic antibody, adalimumab	269:333	Here, we examined the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab.
33107910	4	15	theme	mutant	552:557	arg1	Fab					559:561	Expressed mutant Fab	542:561	Expressed mutant Fab	542:561	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	5	16	theme	Fab	685:687	arg1	aggregation					670:680	aggregation	670:680	aggregation of Fab upon pH shift-induced stress	670:716	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	7	17	theme	wild-type	1199:1207	arg1	Fab					1209:1211	wild-type Fab	1199:1211	wild-type Fab	1199:1211	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	6	18	theme	antigenicity	1014:1025	arg1	suppression					999:1009	the suppression	995:1009	the suppression of antigenicity	995:1025	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	5	19	theme	L-glyco	792:798	arg1	Fab					800:802	L-glyco Fab	792:802	L-glyco Fab	792:802	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	3	20	theme	Fab	436:438	arg1	region					415:420	the H chain constant region	394:420	the H chain constant region of adalimumab Fab	394:438	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	0	21	theme	adalimumab	58:67	arg1	Fab					69:71	adalimumab Fab	58:71	adalimumab Fab secreted from Pichia pastoris	58:101	Glycosylation decreases aggregation and immunogenicity of adalimumab Fab secreted from Pichia pastoris.
33107910	6	22	theme	wild-type	932:940	arg1	Fabs					942:945	glycosylated and wild-type Fabs	915:945	glycosylated and wild-type Fabs	915:945	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	7	23	theme	Fab	1077:1079	arg1	behaviour					1060:1068	the pharmacokinetic behaviour	1040:1068	the pharmacokinetic behaviour of the Fab	1040:1079	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	23	theme	Fab	1077:1079	arg1	Fab					1090:1092	L-glyco Fab	1082:1092	L-glyco Fab	1082:1092	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	23	theme	Fab	1077:1079	arg1	Fab					1106:1108	S-glyco Fab	1098:1108	S-glyco Fab	1098:1108	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	3	24	theme	L178N	499:503	arg1	Fab					505:507	the H:L178N Fab	493:507	the H:L178N Fab	493:507	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	7	25	theme	Fab	1106:1108	arg1	Analysis					1028:1035	Analysis	1028:1035	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab	1028:1108	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	26	theme	Fabs	1156:1159	arg1	half-lives					1129:1138	the half-lives	1125:1138	the half-lives of glycosylated Fabs in the rats	1125:1171	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	26	theme	Fabs	1156:1159	arg1	shorter					1178:1184	shorter	1178:1184	shorter	1178:1184	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	3	27	theme	Pichia	525:530	arg1	pastoris					532:539	Pichia pastoris	525:539	Pichia pastoris	525:539	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	2	28	from	effect	242:247	arg1	properties					273:282	the properties	269:282	the properties of the Fab of the therapeutic antibody, adalimumab	269:333	Here, we examined the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab.
33107910	1	29	theme	several	198:204	arg1	therapeutics					206:217	several therapeutics	198:217	several therapeutics	198:217	Glycoengineering of therapeutic proteins has been applied to improve the clinical efficacy of several therapeutics.
33107910	5	30	theme	S-glyco	743:749	arg1	Fab					751:753	S-glyco Fab	743:753	S-glyco Fab	743:753	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	6	31	theme	antigenicity	899:910	arg1	comparison					881:890	the comparison	877:890	the comparison of the antigenicity of glycosylated and wild-type Fabs in mice	877:953	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	8	32	theme	elimination	1397:1407	arg1	half-life					1409:1417	the elimination half-life	1393:1417	the elimination half-life	1393:1417	Thus, we demonstrated that the glycan chain influences Fab aggregation and immunogenicity, and glycosylation reduces the elimination half-life in vivo.
33107910	2	33	theme	antibody	314:321	arg1	Fab					291:293	the Fab	287:293	the Fab of the therapeutic antibody, adalimumab	287:333	Here, we examined the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab.
33107910	3	34	theme	adalimumab	425:434	arg1	Fab					436:438	adalimumab Fab	425:438	adalimumab Fab	425:438	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	2	35	gly	glycosylation	252:264	arg1	Fab					291:293	the Fab	287:293	the Fab of the therapeutic antibody, adalimumab	287:333	Here, we examined the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab.
33107910	7	36	theme	S-glyco	1263:1269	arg1	Fab					1271:1273	S-glyco Fab	1263:1273	S-glyco Fab	1263:1273	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	2	37	theme	therapeutic	302:312	arg1	adalimumab					324:333	adalimumab	324:333	adalimumab	324:333	Here, we examined the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab.
33107910	2	37	theme	therapeutic	302:312	arg1	antibody					314:321	the therapeutic antibody	298:321	the therapeutic antibody	298:321	Here, we examined the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab.
33107910	7	38	theme	L-glyco	1219:1225	arg1	Fab					1227:1229	L-glyco Fab	1219:1229	L-glyco Fab having a shorter half-life than S-glyco Fab	1219:1273	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	39	theme	S-glyco	1098:1104	arg1	Fab					1106:1108	S-glyco Fab	1098:1108	S-glyco Fab	1098:1108	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	6	40	from	comparison	881:890	arg1	mice					950:953	mice	950:953	mice	950:953	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	1	41	theme	therapeutic	124:134	arg1	proteins					136:143	therapeutic proteins	124:143	therapeutic proteins	124:143	Glycoengineering of therapeutic proteins has been applied to improve the clinical efficacy of several therapeutics.
33107910	4	42	theme	glycan	588:593	arg1	chains					595:600	long and short glycan chains	573:600	long and short glycan chains	573:600	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	3	43	theme	constant	406:413	arg1	region					415:420	the H chain constant region	394:420	the H chain constant region of adalimumab Fab	394:438	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	6	44	from	antigenicity	899:910	arg1	mice					950:953	mice	950:953	mice	950:953	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	4	45	theme	L-glyco	603:609	arg1	Fab					611:613	L-glyco Fab	603:613	L-glyco Fab	603:613	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	1	46	theme	therapeutics	206:217	arg1	efficacy					186:193	the clinical efficacy	173:193	the clinical efficacy of several therapeutics	173:217	Glycoengineering of therapeutic proteins has been applied to improve the clinical efficacy of several therapeutics.
33107910	3	47	theme	site-directed	448:460	arg1	mutagenesis					462:472	site-directed mutagenesis	448:472	site-directed mutagenesis	448:472	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	3	48	theme	region	415:420	arg1	position					378:385	position 178	378:389	position 178 of the H chain constant region of adalimumab Fab	378:438	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	7	49	theme	Fab	1090:1092	arg1	Analysis					1028:1035	Analysis	1028:1035	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab	1028:1108	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	50	from	half-lives	1129:1138	arg1	rats					1168:1171	the rats	1164:1171	the rats	1164:1171	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	3	51	theme	H	398:398	arg1	region					415:420	the H chain constant region	394:420	the H chain constant region of adalimumab Fab	394:438	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	3	52	gly	N-glycosylation	339:353	arg2	site					355:358	An N-glycosylation site	336:358	An N-glycosylation site	336:358	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	3	53	theme	N-glycosylation	339:353	arg1	site					355:358	An N-glycosylation site	336:358	An N-glycosylation site	336:358	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	1	54	theme	proteins	136:143	arg1	Glycoengineering					104:119	Glycoengineering	104:119	Glycoengineering of therapeutic proteins	104:143	Glycoengineering of therapeutic proteins has been applied to improve the clinical efficacy of several therapeutics.
33107910	3	55	theme	chain	400:404	arg1	region					415:420	the H chain constant region	394:420	the H chain constant region of adalimumab Fab	394:438	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	7	56	from	Fabs	1156:1159	arg1	rats					1168:1171	the rats	1164:1171	the rats	1164:1171	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	6	57	from	mice	950:953	arg1	comparison					881:890	the comparison	877:890	the comparison of the antigenicity of glycosylated and wild-type Fabs in mice	877:953	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	4	58	theme	S-glyco	619:625	arg1	Fab					627:629	S-glyco Fab	619:629	S-glyco Fab	619:629	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	3	59	dep	H	475:475	arg1	L178N					477:481	L178N	477:481	L178N	477:481	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	3	60	dep	introduced	364:373	arg1	H					475:475	H	475:475	H	475:475	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	7	61	contain	having	1231:1236	arg2	half-life					1248:1256	a shorter half-life	1238:1256	a shorter half-life than S-glyco Fab	1238:1273	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	7	61	contain	having	1231:1236	arg1	Fab					1227:1229	L-glyco Fab	1219:1229	L-glyco Fab having a shorter half-life than S-glyco Fab	1219:1273	Analysis of the pharmacokinetic behaviour of the Fab, L-glyco Fab and S-glyco Fab indicated that the half-lives of glycosylated Fabs in the rats were shorter than that of wild-type Fab, with L-glyco Fab having a shorter half-life than S-glyco Fab.
33107910	8	62	theme	Fab	1331:1333	arg1	aggregation					1335:1345	Fab aggregation	1331:1345	Fab aggregation	1331:1345	Thus, we demonstrated that the glycan chain influences Fab aggregation and immunogenicity, and glycosylation reduces the elimination half-life in vivo.
33107910	5	63	theme	shift-induced	697:709	arg1	stress					711:716	pH shift-induced stress	694:716	pH shift-induced stress	694:716	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	5	64	theme	S-glyco	854:860	arg1	Fab					862:864	the S-glyco Fab	850:864	the S-glyco Fab	850:864	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	4	65	theme	long	573:576	arg1	chains					595:600	long and short glycan chains	573:600	long and short glycan chains	573:600	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	6	66	gly	glycosylated	915:926	arg1	Fabs					942:945	glycosylated and wild-type Fabs	915:945	glycosylated and wild-type Fabs	915:945	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
33107910	5	67	theme	pH	694:695	arg1	stress					711:716	pH shift-induced stress	694:716	pH shift-induced stress	694:716	Under the condition of aggregation of Fab upon pH shift-induced stress, both of L-glyco Fab and S-glyco Fab were less prone to aggregation, with L-glyco Fab suppressing aggregation more effectively than the S-glyco Fab.
33107910	4	68	dep	contained	563:571	arg1	Fab					611:613	L-glyco Fab	603:613	L-glyco Fab	603:613	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	4	68	dep	contained	563:571	arg1	Fab					627:629	S-glyco Fab	619:629	S-glyco Fab	619:629	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	4	69	contain	contained	563:571	arg1	Fab					559:561	Expressed mutant Fab	542:561	Expressed mutant Fab	542:561	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	4	69	contain	contained	563:571	arg2	chains					595:600	long and short glycan chains	573:600	long and short glycan chains	573:600	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	8	70	theme	glycan	1307:1312	arg1	chain					1314:1318	the glycan chain	1303:1318	the glycan chain	1303:1318	Thus, we demonstrated that the glycan chain influences Fab aggregation and immunogenicity, and glycosylation reduces the elimination half-life in vivo.
33107910	4	71	theme	short	582:586	arg1	chains					595:600	long and short glycan chains	573:600	long and short glycan chains	573:600	Expressed mutant Fab contained long and short glycan chains (L-glyco Fab and S-glyco Fab, respectively).
33107910	0	72	theme	Fab	69:71	arg1	aggregation					24:34	aggregation	24:34	aggregation	24:34	Glycosylation decreases aggregation and immunogenicity of adalimumab Fab secreted from Pichia pastoris.
33107910	0	72	theme	Fab	69:71	arg1	immunogenicity					40:53	immunogenicity	40:53	immunogenicity	40:53	Glycosylation decreases aggregation and immunogenicity of adalimumab Fab secreted from Pichia pastoris.
33107910	2	73	theme	glycosylation	252:264	arg1	effect					242:247	the effect	238:247	the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab	238:333	Here, we examined the effect of glycosylation on the properties of the Fab of the therapeutic antibody, adalimumab.
33107910	3	74	theme	H	497:497	arg1	Fab					505:507	the H:L178N Fab	493:507	the H:L178N Fab	493:507	An N-glycosylation site was introduced at position 178 of the H chain constant region of adalimumab Fab through site-directed mutagenesis (H:L178N Fab), and the H:L178N Fab was produced in Pichia pastoris.
33107910	6	75	theme	Fabs	942:945	arg1	antigenicity					899:910	the antigenicity	895:910	the antigenicity of glycosylated and wild-type Fabs in mice	895:953	Moreover, the comparison of the antigenicity of glycosylated and wild-type Fabs in mice revealed that glycosylation resulted in the suppression of antigenicity.
32767558	4	0	theme	1:1	715:717	arg1	1:4					722:724	1:1 to 1:4	715:724	1:1 to 1:4	715:724	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	4	0	theme	1:1	715:717	arg1	oligochitosan					700:712	oligochitosan	700:712	oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein)	700:772	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	1	1	theme	proteins	230:237	arg1	application					211:221	the application	207:221	the application of pea proteins in food and nutritional applications	207:274	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	7	2	theme	emulsifying	1229:1239	arg1	activity					1241:1248	the emulsifying activity	1225:1248	the emulsifying activity	1225:1248	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	3	3	theme	structural	509:518	arg1	properties					535:544	the structural and functional properties	505:544	the structural and functional properties of pea seed legumin	505:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	4	4	theme	Different	579:587	arg1	OLCs					631:634	OLCs	631:634	OLCs	631:634	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	4	4	theme	Different	579:587	arg1	complexes					620:628	Different oligochitosan-modified legumin complexes	579:628	Different oligochitosan-modified legumin complexes (OLCs)	579:635	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	7	5	dep	in	1314:1315	arg1	vitro					1317:1321	vitro	1317:1321	vitro	1317:1321	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	9	6	theme	protein-oligochitosan	1712:1732	arg1	complex					1734:1740	protein-oligochitosan complex	1712:1740	protein-oligochitosan complex	1712:1740	This study will facilitate the legumin functionalization by the glycosylation approach to fabricate protein-oligochitosan complex for potential food and nutritional applications.
32767558	7	7	theme	OLCs	1350:1353	arg1	stability					1280:1288	emulsification stability	1265:1288	emulsification stability	1265:1288	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	7	7	theme	OLCs	1350:1353	arg1	stability					1299:1307	thermal stability	1291:1307	thermal stability	1291:1307	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	7	7	theme	OLCs	1350:1353	arg1	stability					1333:1341	in vitro digestive stability	1314:1341	in vitro digestive stability	1314:1341	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	3	8	theme	pea	549:551	arg1	legumin					558:564	pea seed legumin	549:564	pea seed legumin	549:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	7	9	dep	stability	1280:1288	arg1	the					1261:1263	the	1261:1263	the	1261:1263	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	1	10	theme	food	242:245	arg1	applications					263:274	food and nutritional applications	242:274	food and nutritional applications	242:274	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	9	11	theme	potential	1746:1754	arg1	applications					1777:1788	potential food and nutritional applications	1746:1788	potential food and nutritional applications	1746:1788	This study will facilitate the legumin functionalization by the glycosylation approach to fabricate protein-oligochitosan complex for potential food and nutritional applications.
32767558	4	12	theme	U g-1	759:763	arg1	protein					765:771	10 U g-1 protein	756:771	10 U g-1 protein	756:771	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	4	12	theme	U g-1	759:763	arg1	transglutaminase					738:753	transglutaminase	738:753	transglutaminase (10 U g-1 protein)	738:772	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	3	13	theme	seed	553:556	arg1	legumin					558:564	pea seed legumin	549:564	pea seed legumin	549:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	3	14	theme	oligochitosan	474:486	arg1	glycosylation					488:500	transglutaminase-induced oligochitosan glycosylation	449:500	transglutaminase-induced oligochitosan glycosylation	449:500	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	3	15	theme	glycosylation	488:500	arg1	effect					439:444	the effect	435:444	the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin	435:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	7	16	theme	digestive	1323:1331	arg1	stability					1333:1341	in vitro digestive stability	1314:1341	in vitro digestive stability	1314:1341	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	5	17	theme	free	873:876	arg1	analysis					884:891	free amino analysis	873:891	free amino analysis	873:891	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	6	18	theme	microscopy	1089:1098	arg1	analysis					1100:1107	scanning electron microscopy analysis	1071:1107	scanning electron microscopy analysis	1071:1107	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	4	19	theme	legumin	612:618	arg1	OLCs					631:634	OLCs	631:634	OLCs	631:634	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	4	19	theme	legumin	612:618	arg1	complexes					620:628	Different oligochitosan-modified legumin complexes	579:628	Different oligochitosan-modified legumin complexes (OLCs)	579:635	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	4	20	theme	oligochitosan-modified	589:610	arg1	OLCs					631:634	OLCs	631:634	OLCs	631:634	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	4	20	theme	oligochitosan-modified	589:610	arg1	complexes					620:628	Different oligochitosan-modified legumin complexes	579:628	Different oligochitosan-modified legumin complexes (OLCs)	579:635	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	2	21	theme	functional	373:382	arg1	properties					384:393	the functional properties	369:393	the functional properties of pea proteins	369:409	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	5	22	theme	sulfate-polyacrylamide	801:822	arg1	SDS-PAGE					845:852	SDS-PAGE	845:852	SDS-PAGE	845:852	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	5	22	theme	sulfate-polyacrylamide	801:822	arg1	electrophoresis					828:842	sodium dodecyl sulfate-polyacrylamide gel electrophoresis	786:842	sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)	786:853	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	8	23	theme	Oligochitosan	1434:1446	arg1	glycosylation					1448:1460	CONCLUSION Oligochitosan glycosylation	1423:1460	CONCLUSION Oligochitosan glycosylation	1423:1460	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	2	24	dep	influence	318:326	arg1	change					362:367	change	362:367	change the functional properties of pea proteins	362:409	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	7	25	theme	thermal	1291:1297	arg1	stability					1299:1307	thermal stability	1291:1307	thermal stability	1291:1307	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	4	26	theme	legumin	689:695	arg1	ratios					679:684	different molar ratios	663:684	different molar ratios of legumin	663:695	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	5	27	theme	gel	824:826	arg1	SDS-PAGE					845:852	SDS-PAGE	845:852	SDS-PAGE	845:852	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	5	27	theme	gel	824:826	arg1	electrophoresis					828:842	sodium dodecyl sulfate-polyacrylamide gel electrophoresis	786:842	sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)	786:853	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	1	28	theme	nutritional	251:261	arg1	applications					263:274	food and nutritional applications	242:274	food and nutritional applications	242:274	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	8	29	dep	in	1582:1583	arg1	vitro					1585:1589	vitro	1585:1589	vitro	1585:1589	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	3	30	gly	glycosylation	488:500	arg1	legumin					558:564	pea seed legumin	549:564	pea seed legumin	549:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	1	31	theme	soybean	176:182	arg1	proteins					184:191	soybean proteins	176:191	soybean proteins	176:191	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	5	32	theme	electrophoresis	828:842	arg1	Results					775:781	Results	775:781	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis	775:891	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	6	33	theme	electron	1080:1087	arg1	microscopy					1089:1098	scanning electron microscopy	1071:1098	scanning electron microscopy analysis	1071:1107	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	9	34	theme	nutritional	1765:1775	arg1	applications					1777:1788	potential food and nutritional applications	1746:1788	potential food and nutritional applications	1746:1788	This study will facilitate the legumin functionalization by the glycosylation approach to fabricate protein-oligochitosan complex for potential food and nutritional applications.
32767558	7	35	theme	emulsification	1265:1278	arg1	stability					1280:1288	emulsification stability	1265:1288	emulsification stability	1265:1288	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	3	36	theme	legumin	558:564	arg1	properties					535:544	the structural and functional properties	505:544	the structural and functional properties of pea seed legumin	505:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	2	37	theme	promising	296:304	arg1	Glycosylation					277:289	Glycosylation	277:289	Glycosylation	277:289	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	2	37	theme	promising	296:304	arg1	approach					306:313	a promising approach	294:313	a promising approach to influence the protein structure and in turn change the functional properties of pea proteins	294:409	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	8	38	theme	thermal	1559:1565	arg1	stability					1567:1575	thermal stability	1559:1575	thermal stability	1559:1575	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	10	39	theme	Chemical	1809:1816	arg1	Industry					1818:1825	Chemical Industry	1809:1825	Chemical Industry	1809:1825	© 2020 Society of Chemical Industry.
32767558	6	40	theme	OLC	1155:1157	arg1	samples					1159:1165	the different OLC samples	1141:1165	the different OLC samples	1141:1165	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	2	41	theme	proteins	402:409	arg1	properties					384:393	the functional properties	369:393	the functional properties of pea proteins	369:409	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	8	42	theme	digestive	1591:1599	arg1	stability					1601:1609	in vitro digestive stability	1582:1609	in vitro digestive stability	1582:1609	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	4	43	theme	different	663:671	arg1	ratios					679:684	different molar ratios	663:684	different molar ratios of legumin	663:695	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	3	44	dep	RESULTS	412:418	arg1	study					428:432	this study	423:432	this study	423:432	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	5	45	theme	amino	878:882	arg1	analysis					884:891	free amino analysis	873:891	free amino analysis	873:891	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	2	46	theme	pea	398:400	arg1	proteins					402:409	pea proteins	398:409	pea proteins	398:409	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	6	47	theme	scanning	1071:1078	arg1	microscopy					1089:1098	scanning electron microscopy	1071:1098	scanning electron microscopy analysis	1071:1107	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	7	48	theme	untreated	1404:1412	arg1	legumin					1414:1420	the untreated legumin	1400:1420	the untreated legumin	1400:1420	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	5	49	theme	oligochitosan	1015:1027	arg1	dose					1003:1006	the applying dose	990:1006	the applying dose of the oligochitosan	990:1027	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	9	50	theme	glycosylation	1676:1688	arg1	approach					1690:1697	the glycosylation approach	1672:1697	the glycosylation approach to fabricate protein-oligochitosan complex for potential food and nutritional applications	1672:1788	This study will facilitate the legumin functionalization by the glycosylation approach to fabricate protein-oligochitosan complex for potential food and nutritional applications.
32767558	5	51	theme	glucosamine	856:866	arg1	Results					775:781	Results	775:781	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis	775:891	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	0	52	theme	pea	44:46	arg1	legumin					53:59	the pea seed legumin	40:59	the pea seed legumin	40:59	The structure and stability analysis of the pea seed legumin glycosylated by oligochitosan.
32767558	5	53	theme	analysis	884:891	arg1	Results					775:781	Results	775:781	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis	775:891	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	8	54	theme	in	1582:1583	arg1	stability					1601:1609	in vitro digestive stability	1582:1609	in vitro digestive stability	1582:1609	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	8	55	theme	CONCLUSION	1423:1432	arg1	glycosylation					1448:1460	CONCLUSION Oligochitosan glycosylation	1423:1460	CONCLUSION Oligochitosan glycosylation	1423:1460	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	2	56	theme	protein	332:338	arg1	structure					340:348	the protein structure	328:348	the protein structure	328:348	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	9	57	dep	potential	1746:1754	arg1	food					1756:1759	food	1756:1759	food	1756:1759	This study will facilitate the legumin functionalization by the glycosylation approach to fabricate protein-oligochitosan complex for potential food and nutritional applications.
32767558	6	58	theme	different	1187:1195	arg1	extents					1197:1203	different extents	1187:1203	different extents	1187:1203	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	3	59	theme	transglutaminase-induced	449:472	arg1	glycosylation					488:500	transglutaminase-induced oligochitosan glycosylation	449:500	transglutaminase-induced oligochitosan glycosylation	449:500	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	6	60	theme	samples	1159:1165	arg1	structure					1128:1136	the structure	1124:1136	the structure of the different OLC samples	1124:1165	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	3	61	from	effect	439:444	arg1	properties					535:544	the structural and functional properties	505:544	the structural and functional properties of pea seed legumin	505:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	9	62	theme	legumin	1643:1649	arg1	functionalization					1651:1667	the legumin functionalization	1639:1667	the legumin functionalization	1639:1667	This study will facilitate the legumin functionalization by the glycosylation approach to fabricate protein-oligochitosan complex for potential food and nutritional applications.
32767558	8	63	theme	legumin	1496:1502	arg1	structure					1479:1487	the structure	1475:1487	the structure of the legumin	1475:1502	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	1	64	theme	pea	124:126	arg1	proteins					128:135	pea proteins	124:135	pea proteins	124:135	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	4	65	dep	1:4	722:724	arg1	to					719:720	to	719:720	to	719:720	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	6	66	theme	Infrared	1030:1037	arg1	spectroscopy					1039:1050	Infrared spectroscopy	1030:1050	Infrared spectroscopy	1030:1050	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	1	67	from	application	211:221	arg1	applications					263:274	food and nutritional applications	242:274	food and nutritional applications	242:274	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	5	68	theme	applying	994:1001	arg1	dose					1003:1006	the applying dose	990:1006	the applying dose of the oligochitosan	990:1027	Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), glucosamine, and free amino analysis showed that the legumin could be covalently bonded with the oligochitosan and were influenced by the applying dose of the oligochitosan.
32767558	1	69	theme	proteins	128:135	arg1	functionality					107:119	The functionality	103:119	The functionality of pea proteins	103:135	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	1	69	theme	proteins	128:135	arg1	weak					151:154	weak	151:154	weak	151:154	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	6	70	theme	different	1145:1153	arg1	samples					1159:1165	the different OLC samples	1141:1165	the different OLC samples	1141:1165	Infrared spectroscopy, fluorescence, and scanning electron microscopy analysis indicated that the structure of the different OLC samples could be changed to different extents.
32767558	2	71	dep	approach	306:313	arg1	influence					318:326	influence	318:326	to influence the protein structure	315:348	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	2	71	dep	approach	306:313	arg1	turn					357:360	turn	357:360	turn	357:360	Glycosylation is a promising approach to influence the protein structure and in turn change the functional properties of pea proteins.
32767558	0	72	theme	legumin	53:59	arg1	stability					18:26	stability	18:26	stability	18:26	The structure and stability analysis of the pea seed legumin glycosylated by oligochitosan.
32767558	0	72	theme	legumin	53:59	arg1	structure					4:12	structure	4:12	structure	4:12	The structure and stability analysis of the pea seed legumin glycosylated by oligochitosan.
32767558	7	73	theme	in	1314:1315	arg1	stability					1333:1341	in vitro digestive stability	1314:1341	in vitro digestive stability	1314:1341	Moreover, although the emulsifying activity decreased, the emulsification stability, thermal stability, and in vitro digestive stability of the OLCs were remarkably improved relative to that of the untreated legumin.
32767558	0	74	dep	structure	4:12	arg1	The					0:2	The	0:2	The	0:2	The structure and stability analysis of the pea seed legumin glycosylated by oligochitosan.
32767558	0	74	dep	structure	4:12	arg1	analysis					28:35	analysis	28:35	analysis	28:35	The structure and stability analysis of the pea seed legumin glycosylated by oligochitosan.
32767558	1	75	dep	BACKGROUND	92:101	arg1	functionality					107:119	The functionality	103:119	The functionality of pea proteins	103:135	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	1	75	dep	BACKGROUND	92:101	arg1	weak					151:154	weak	151:154	weak	151:154	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
32767558	4	76	theme	molar	673:677	arg1	ratios					679:684	different molar ratios	663:684	different molar ratios of legumin	663:695	Different oligochitosan-modified legumin complexes (OLCs) were prepared by applying different molar ratios of legumin to oligochitosan (1:1 to 1:4) induced by transglutaminase (10 U g-1 protein).
32767558	0	77	theme	seed	48:51	arg1	legumin					53:59	the pea seed legumin	40:59	the pea seed legumin	40:59	The structure and stability analysis of the pea seed legumin glycosylated by oligochitosan.
32767558	8	78	theme	emulsification	1533:1546	arg1	stability					1548:1556	emulsification stability	1533:1556	emulsification stability	1533:1556	CONCLUSION Oligochitosan glycosylation could change the structure of the legumin and consequently improve its emulsification stability, thermal stability, and in vitro digestive stability.
32767558	3	79	theme	functional	524:533	arg1	properties					535:544	the structural and functional properties	505:544	the structural and functional properties of pea seed legumin	505:564	RESULTS In this study, the effect of transglutaminase-induced oligochitosan glycosylation on the structural and functional properties of pea seed legumin was studied.
32767558	1	80	theme	pea	226:228	arg1	proteins					230:237	pea proteins	226:237	pea proteins	226:237	BACKGROUND The functionality of pea proteins is relatively weak relative to that of soybean proteins, which limits the application of pea proteins in food and nutritional applications.
34869209	5	0	theme	RBD	638:640	arg1	patterns					597:604	the site-specific glycosylation patterns	565:604	the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	565:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	5	1	theme	HEK293	613:618	arg1	RBD					638:640	the HEK293 recombinant spike RBD and S1 domains	609:655	RBD	638:640	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	12	2	theme	recombinant	1687:1697	arg1	S1					1699:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported.
34869209	11	3	theme	cell	1534:1537	arg1	virus					1545:1549	the Vero E6 cell whole virus	1522:1549	the Vero E6 cell whole virus	1522:1549	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	5	4	theme	spike	632:636	arg1	RBD					638:640	the HEK293 recombinant spike RBD and S1 domains	609:655	RBD	638:640	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	11	5	theme	complex	1468:1474	arg1	glycan					1476:1481	complex glycan	1468:1481	complex glycan	1468:1481	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	5	6	theme	glycosylation	583:595	arg1	patterns					597:604	the site-specific glycosylation patterns	565:604	the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	565:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	8	7	link	HEK293-derived	1007:1020	arg1	S1					1022:1023	HEK293-derived S1	1007:1023	HEK293-derived S1	1007:1023	N-glycans identified in HEK293-derived S1 were structurally diverse.
34869209	12	8	theme	CHO-	1661:1664	arg1	S1					1699:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported.
34869209	1	9	gly	N-glycosylation	209:223	arg2	sites					225:229	22 predicted N-glycosylation sites	196:229	22 predicted N-glycosylation sites	196:229	The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer.
34869209	1	9	gly	N-glycosylation	209:223	arg2	22					196:197	22	196:197	22	196:197	The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer.
34869209	10	10	gly	N-glycosites	1244:1255	arg2	N-glycosites					1244:1255	N-glycosites	1244:1255	N-glycosites local to the mutation site	1244:1282	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	5	11	gly	glycosylation	583:595	arg1	RBD					638:640	the HEK293 recombinant spike RBD and S1 domains	609:655	RBD	638:640	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	5	11	gly	glycosylation	583:595	arg1	domains					649:655	the HEK293 recombinant spike RBD and S1 domains	609:655	domains	649:655	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	5	11	gly	glycosylation	583:595	arg1	spike					679:683	the intact spike	668:683	the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	609:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	14	12	theme	type	2055:2058	arg1	O-glycans					2060:2068	Core 1 and 2 type O-glycans	2042:2068	O-glycans	2060:2068	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	0	13	theme	D614G	120:124	arg1	Strains					126:132	Viral WA1 and D614G Strains	106:132	Viral WA1 and D614G Strains	106:132	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	2	14	theme	O-glycosites	294:305	arg1	number					284:289	the number	280:289	the number of O-glycosites	280:305	It is also O-glycosylated, although the number of O-glycosites is less defined.
34869209	1	15	theme	predicted	199:207	arg1	sites					225:229	22 predicted N-glycosylation sites	196:229	22 predicted N-glycosylation sites	196:229	The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer.
34869209	14	16	theme	Core	2042:2045	arg1	range					2033:2037	a similar range	2023:2037	a similar range of Core 1 and 2 type O-glycans	2023:2068	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	7	17	theme	mass	964:967	arg1	spectrometer					969:980	Tribrid mass spectrometer	956:980	Tribrid mass spectrometer	956:980	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	5	18	theme	domains	649:655	arg1	patterns					597:604	the site-specific glycosylation patterns	565:604	the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	565:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	15	19	theme	glycosylation	2213:2225	arg1	profile					2227:2233	the glycosylation profile	2209:2233	the glycosylation profile	2209:2233	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	4	20	theme	spike	425:429	arg1	monomer					431:437	The spike monomer	421:437	The spike monomer	421:437	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	11	21	theme	HEK293-derived	1414:1427	arg1	S1					1429:1430	recombinant HEK293-derived S1	1402:1430	recombinant HEK293-derived S1	1402:1430	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	5	22	theme	whole	702:706	arg1	virus					708:712	the whole virus	698:712	the whole virus produced in Vero cells	698:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	1	23	theme	spike	150:154	arg1	protein					156:162	The SARS-CoV-2 spike protein	135:162	The SARS-CoV-2 spike protein	135:162	The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer.
34869209	10	24	theme	glycosylation	1367:1379	arg1	machinery					1381:1389	glycosylation machinery	1367:1389	glycosylation machinery	1367:1389	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	10	25	theme	cell-derived	1188:1199	arg1	WA1					1201:1203	the whole cell-derived WA1	1178:1203	the whole cell-derived WA1	1178:1203	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	0	26	theme	Recombinant	82:92	arg1	Protein					94:100	Recombinant Protein	82:100	Recombinant Protein	82:100	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	14	27	used	occupied	2011:2018	arg2	O-glycosites					1930:1941	The O-glycosites	1926:1941	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523,	1926:2004	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	7	28	theme	hydrophilic	873:883	arg1	HILIC					913:917	HILIC	913:917	HILIC	913:917	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	7	28	theme	hydrophilic	873:883	arg1	chromatography					897:910	hydrophilic interaction chromatography	873:910	hydrophilic interaction chromatography (HILIC)	873:918	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	12	29	theme	glycosylation	1625:1637	arg1	patterns					1639:1646	glycosylation patterns	1625:1646	glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported	1625:1745	This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported.
34869209	3	30	theme	protein	355:361	arg1	glycans					363:369	spike protein glycans	349:369	spike protein glycans	349:369	Recent studies show that spike protein glycans play critical roles in viral entry and infection.
34869209	4	31	theme	receptor-binding	476:491	arg1	RBD					501:503	RBD	501:503	RBD	501:503	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	4	31	theme	receptor-binding	476:491	arg1	domain					493:498	a receptor-binding domain	474:498	a receptor-binding domain (RBD) within the S1 domain	474:525	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	14	32	theme	similar	2025:2031	arg1	range					2033:2037	a similar range	2023:2037	a similar range of Core 1 and 2 type O-glycans	2023:2068	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	16	33	theme	SARS-CoV-2	2236:2245	arg1	glycans					2253:2259	SARS-CoV-2 spike glycans	2236:2259	SARS-CoV-2 spike glycans	2236:2259	SARS-CoV-2 spike glycans are associated with host ACE2 receptor interaction efficiency.
34869209	5	34	theme	spike	679:683	arg1	patterns					597:604	the site-specific glycosylation patterns	565:604	the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	565:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	13	35	gly	O-glycosites	1852:1863	arg2	O-glycosites					1852:1863	O-glycosites	1852:1863	O-glycosites	1852:1863	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	13	36	contain	possessed	1831:1839	arg1	proteins					1822:1829	HEK293 recombinant proteins	1803:1829	HEK293 recombinant proteins	1803:1829	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	13	36	contain	possessed	1831:1839	arg2	range					1843:1847	a range	1841:1847	a range of O-glycosites	1841:1863	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	10	37	theme	spike	1215:1219	arg1	proteins					1221:1228	D614G spike proteins	1209:1228	D614G spike proteins	1209:1228	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	0	38	theme	WA1	112:114	arg1	Strains					126:132	Viral WA1 and D614G Strains	106:132	Viral WA1 and D614G Strains	106:132	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	17	39	theme	downstream	2481:2490	arg1	investigations					2492:2505	suite downstream investigations	2475:2505	suite downstream investigations	2475:2505	Therefore, understanding such differences will serve to better understand these host-pathogen interactions and inform the choice of cell substrates to suite downstream investigations.
34869209	13	40	theme	HEK293	1803:1808	arg1	proteins					1822:1829	HEK293 recombinant proteins	1803:1829	HEK293 recombinant proteins	1803:1829	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	0	41	theme	Site-Specific	0:12	arg1	Patterns					28:35	Site-Specific Glycosylation Patterns	0:35	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein	0:67	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	13	42	with	consistent	1883:1892	arg1	glycans					1917:1923	Core type 1 and 2 glycans	1899:1923	glycans	1917:1923	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	13	42	with	consistent	1883:1892	arg1	type					1904:1907	Core type 1 and 2 glycans	1899:1923	type	1904:1907	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	4	43	contain	has	439:441	arg2	S1					459:460	S1	459:460	S1	459:460	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	4	43	contain	has	439:441	arg2	subdomains					447:456	two subdomains	443:456	two subdomains	443:456	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	4	43	contain	has	439:441	arg2	RBD					501:503	RBD	501:503	RBD	501:503	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	4	43	contain	has	439:441	arg2	S2					466:467	S2	466:467	S2	466:467	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	4	43	contain	has	439:441	arg1	monomer					431:437	The spike monomer	421:437	The spike monomer	421:437	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	4	43	contain	has	439:441	arg2	domain					493:498	a receptor-binding domain	474:498	a receptor-binding domain (RBD) within the S1 domain	474:525	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	5	44	theme	Vero	726:729	arg1	cells					731:735	Vero cells	726:735	Vero cells	726:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	3	45	theme	viral	394:398	arg1	entry					400:404	viral entry	394:404	viral entry	394:404	Recent studies show that spike protein glycans play critical roles in viral entry and infection.
34869209	9	46	link	HEK293-derived	1071:1084	arg1	RBD					1086:1088	the HEK293-derived RBD	1067:1088	the HEK293-derived RBD	1067:1088	Those found in the HEK293-derived RBD were highly similar to those in HEK293 S1 where N-glycosites were shared.
34869209	10	47	theme	mutation	1270:1277	arg1	site					1279:1282	the mutation site	1266:1282	the mutation site	1266:1282	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	0	48	theme	Spike	55:59	arg1	Protein					61:67	the SARS-CoV-2 Spike Protein	40:67	the SARS-CoV-2 Spike Protein	40:67	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	16	49	theme	interaction	2300:2310	arg1	efficiency					2312:2321	host ACE2 receptor interaction efficiency	2281:2321	host ACE2 receptor interaction efficiency	2281:2321	SARS-CoV-2 spike glycans are associated with host ACE2 receptor interaction efficiency.
34869209	14	50	theme	RBD	1969:1971	arg1	constructs					1973:1982	the S1 and RBD constructs	1958:1982	the S1 and RBD constructs	1958:1982	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	14	50	theme	RBD	1969:1971	arg1	sites					1985:1989	sites T323 and T523	1985:2003	sites T323 and T523	1985:2003	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	9	51	theme	HEK293-derived	1071:1084	arg1	RBD					1086:1088	the HEK293-derived RBD	1067:1088	the HEK293-derived RBD	1067:1088	Those found in the HEK293-derived RBD were highly similar to those in HEK293 S1 where N-glycosites were shared.
34869209	17	52	theme	host-pathogen	2404:2416	arg1	interactions					2418:2429	these host-pathogen interactions	2398:2429	these host-pathogen interactions	2398:2429	Therefore, understanding such differences will serve to better understand these host-pathogen interactions and inform the choice of cell substrates to suite downstream investigations.
34869209	13	53	theme	recombinant	1810:1820	arg1	proteins					1822:1829	HEK293 recombinant proteins	1803:1829	HEK293 recombinant proteins	1803:1829	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	15	54	theme	dramatic	2190:2197	arg1	impact					2199:2204	a dramatic impact	2188:2204	a dramatic impact	2188:2204	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	12	55	theme	whole	1715:1719	arg1	spike					1721:1725	the whole spike	1711:1725	the whole spike	1711:1725	This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported.
34869209	2	56	gly	O-glycosites	294:305	arg2	O-glycosites					294:305	O-glycosites	294:305	O-glycosites	294:305	It is also O-glycosylated, although the number of O-glycosites is less defined.
34869209	1	57	gly	glycosylated	175:186	arg1	protein					156:162	The SARS-CoV-2 spike protein	135:162	The SARS-CoV-2 spike protein	135:162	The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer.
34869209	5	58	attach	derived	685:691	arg1	virus					708:712	the whole virus	698:712	the whole virus produced in Vero cells	698:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	5	58	attach	derived	685:691	arg2	spike					679:683	the intact spike	668:683	the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	609:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	6	59	link	cell-derived	747:758	arg1	spike					760:764	The Vero cell-derived spike	738:764	The Vero cell-derived spike from the WA1 strain and a D614G variant	738:804	The Vero cell-derived spike from the WA1 strain and a D614G variant was analyzed.
34869209	7	60	dep	Orbitrap	939:946	arg1	Eclipse					948:954	Eclipse	948:954	Eclipse Tribrid mass spectrometer	948:980	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	16	61	theme	spike	2247:2251	arg1	glycans					2253:2259	SARS-CoV-2 spike glycans	2236:2259	SARS-CoV-2 spike glycans	2236:2259	SARS-CoV-2 spike glycans are associated with host ACE2 receptor interaction efficiency.
34869209	5	62	theme	recombinant	620:630	arg1	RBD					638:640	the HEK293 recombinant spike RBD and S1 domains	609:655	RBD	638:640	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	6	63	theme	cell-derived	747:758	arg1	spike					760:764	The Vero cell-derived spike	738:764	The Vero cell-derived spike from the WA1 strain and a D614G variant	738:804	The Vero cell-derived spike from the WA1 strain and a D614G variant was analyzed.
34869209	15	64	theme	proteins	2170:2177	arg1	production					2150:2159	production	2150:2159	production of these proteins	2150:2177	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	11	65	theme	Vero	1526:1529	arg1	virus					1545:1549	the Vero E6 cell whole virus	1522:1549	the Vero E6 cell whole virus	1522:1549	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	11	66	attach	derived	1509:1515	arg2	WA1					1495:1497	WA1	1495:1497	WA1	1495:1497	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	11	66	attach	derived	1509:1515	arg1	virus					1545:1549	the Vero E6 cell whole virus	1522:1549	the Vero E6 cell whole virus	1522:1549	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	5	67	theme	site-specific	569:581	arg1	patterns					597:604	the site-specific glycosylation patterns	565:604	the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	565:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	9	68	theme	HEK293	1122:1127	arg1	S1					1129:1130	HEK293 S1	1122:1130	HEK293 S1	1122:1130	Those found in the HEK293-derived RBD were highly similar to those in HEK293 S1 where N-glycosites were shared.
34869209	15	69	dep	nature	2115:2120	arg1	the					2104:2106	the	2104:2106	the	2104:2106	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	17	70	theme	such	2349:2352	arg1	differences					2354:2364	such differences	2349:2364	such differences	2349:2364	Therefore, understanding such differences will serve to better understand these host-pathogen interactions and inform the choice of cell substrates to suite downstream investigations.
34869209	2	71	gly	O-glycosylated	255:268	arg1	It					244:245	It	244:245	It	244:245	It is also O-glycosylated, although the number of O-glycosites is less defined.
34869209	13	72	theme	consistent	1883:1892	arg1	compositions					1870:1881	compositions	1870:1881	compositions consistent with Core type 1 and 2 glycans	1870:1923	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	12	73	theme	cell-derived	1674:1685	arg1	S1					1699:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported.
34869209	11	74	used	occupied	1436:1443	arg2	S1					1429:1430	recombinant HEK293-derived S1	1402:1430	recombinant HEK293-derived S1	1402:1430	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	6	75	from	variant	798:804	arg1	spike					760:764	The Vero cell-derived spike	738:764	The Vero cell-derived spike from the WA1 strain and a D614G variant	738:804	The Vero cell-derived spike from the WA1 strain and a D614G variant was analyzed.
34869209	9	76	located	found	1058:1062	arg2	Those					1052:1056	Those	1052:1056	Those	1052:1056	Those found in the HEK293-derived RBD were highly similar to those in HEK293 S1 where N-glycosites were shared.
34869209	9	76	located	found	1058:1062	arg1	RBD					1086:1088	the HEK293-derived RBD	1067:1088	the HEK293-derived RBD	1067:1088	Those found in the HEK293-derived RBD were highly similar to those in HEK293 S1 where N-glycosites were shared.
34869209	13	77	theme	Core	1899:1902	arg1	type					1904:1907	Core type 1 and 2 glycans	1899:1923	type	1904:1907	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	1	78	theme	N-glycosylation	209:223	arg1	sites					225:229	22 predicted N-glycosylation sites	196:229	22 predicted N-glycosylation sites	196:229	The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer.
34869209	14	79	theme	O-glycans	2060:2068	arg1	range					2033:2037	a similar range	2023:2037	a similar range of Core 1 and 2 type O-glycans	2023:2068	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	6	80	from	strain	779:784	arg1	spike					760:764	The Vero cell-derived spike	738:764	The Vero cell-derived spike from the WA1 strain and a D614G variant	738:804	The Vero cell-derived spike from the WA1 strain and a D614G variant was analyzed.
34869209	5	81	theme	intact	672:677	arg1	spike					679:683	the intact spike	668:683	the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells	609:735	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	7	82	theme	Tribrid	956:962	arg1	spectrometer					969:980	Tribrid mass spectrometer	956:980	Tribrid mass spectrometer	956:980	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	15	83	theme	sample	2108:2113	arg1	nature					2115:2120	sample nature	2108:2120	sample nature	2108:2120	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	9	84	gly	N-glycosites	1138:1149	arg2	N-glycosites					1138:1149	N-glycosites	1138:1149	N-glycosites	1138:1149	Those found in the HEK293-derived RBD were highly similar to those in HEK293 S1 where N-glycosites were shared.
34869209	14	85	dep	sites	1985:1989	arg1	T323					1991:1994	T323	1991:1994	T323	1991:1994	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	14	85	dep	sites	1985:1989	arg1	sites					1985:1989	sites T323 and T523	1985:2003	sites T323 and T523	1985:2003	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	14	85	dep	sites	1985:1989	arg1	T523					2000:2003	T523	2000:2003	T523	2000:2003	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	15	86	contain	have	2183:2186	arg1	substrate					2131:2139	cell substrate	2126:2139	cell substrate	2126:2139	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	15	86	contain	have	2183:2186	arg2	impact					2199:2204	a dramatic impact	2188:2204	a dramatic impact	2188:2204	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	15	86	contain	have	2183:2186	arg1	nature					2115:2120	sample nature	2108:2120	sample nature	2108:2120	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	5	87	theme	S1	646:647	arg1	domains					649:655	the HEK293 recombinant spike RBD and S1 domains	609:655	domains	649:655	In this study, we have characterized the site-specific glycosylation patterns of the HEK293 recombinant spike RBD and S1 domains as well as the intact spike derived from the whole virus produced in Vero cells.
34869209	11	88	link	HEK293-derived	1414:1427	arg1	S1					1429:1430	recombinant HEK293-derived S1	1402:1430	recombinant HEK293-derived S1	1402:1430	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	17	89	theme	cell	2456:2459	arg1	substrates					2461:2470	cell substrates	2456:2470	cell substrates	2456:2470	Therefore, understanding such differences will serve to better understand these host-pathogen interactions and inform the choice of cell substrates to suite downstream investigations.
34869209	16	90	theme	ACE2	2286:2289	arg1	efficiency					2312:2321	host ACE2 receptor interaction efficiency	2281:2321	host ACE2 receptor interaction efficiency	2281:2321	SARS-CoV-2 spike glycans are associated with host ACE2 receptor interaction efficiency.
34869209	11	91	theme	recombinant	1402:1412	arg1	S1					1429:1430	recombinant HEK293-derived S1	1402:1430	recombinant HEK293-derived S1	1402:1430	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	1	92	theme	SARS-CoV-2	139:148	arg1	protein					156:162	The SARS-CoV-2 spike protein	135:162	The SARS-CoV-2 spike protein	135:162	The SARS-CoV-2 spike protein is heavily glycosylated, having 22 predicted N-glycosylation sites per monomer.
34869209	10	93	theme	WA1	1201:1203	arg1	Comparison					1164:1173	Comparison	1164:1173	Comparison of the whole cell-derived WA1 and D614G spike proteins	1164:1228	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	12	94	theme	stark	1607:1611	arg1	contrast					1613:1620	stark contrast	1607:1620	stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported	1607:1745	This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported.
34869209	3	95	theme	Recent	324:329	arg1	studies					331:337	Recent studies	324:337	Recent studies	324:337	Recent studies show that spike protein glycans play critical roles in viral entry and infection.
34869209	10	96	theme	whole	1182:1186	arg1	WA1					1201:1203	the whole cell-derived WA1	1178:1203	the whole cell-derived WA1	1178:1203	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	0	97	theme	Viral	106:110	arg1	Strains					126:132	Viral WA1 and D614G Strains	106:132	Viral WA1 and D614G Strains	106:132	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	7	98	theme	interaction	885:895	arg1	HILIC					913:917	HILIC	913:917	HILIC	913:917	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	7	98	theme	interaction	885:895	arg1	chromatography					897:910	hydrophilic interaction chromatography	873:910	hydrophilic interaction chromatography (HILIC)	873:918	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	14	99	theme	S1	1962:1963	arg1	constructs					1973:1982	the S1 and RBD constructs	1958:1982	the S1 and RBD constructs	1958:1982	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	14	99	theme	S1	1962:1963	arg1	sites					1985:1989	sites T323 and T523	1985:2003	sites T323 and T523	1985:2003	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	17	100	theme	substrates	2461:2470	arg1	choice					2446:2451	the choice	2442:2451	the choice of cell substrates to suite downstream investigations	2442:2505	Therefore, understanding such differences will serve to better understand these host-pathogen interactions and inform the choice of cell substrates to suite downstream investigations.
34869209	10	101	theme	proteins	1221:1228	arg1	Comparison					1164:1173	Comparison	1164:1173	Comparison of the whole cell-derived WA1 and D614G spike proteins	1164:1228	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	3	102	theme	spike	349:353	arg1	glycans					363:369	spike protein glycans	349:369	spike protein glycans	349:369	Recent studies show that spike protein glycans play critical roles in viral entry and infection.
34869209	17	103	theme	suite	2475:2479	arg1	investigations					2492:2505	suite downstream investigations	2475:2505	suite downstream investigations	2475:2505	Therefore, understanding such differences will serve to better understand these host-pathogen interactions and inform the choice of cell substrates to suite downstream investigations.
34869209	10	104	theme	D614G	1209:1213	arg1	proteins					1221:1228	D614G spike proteins	1209:1228	D614G spike proteins	1209:1228	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	0	105	theme	Glycosylation	14:26	arg1	Patterns					28:35	Site-Specific Glycosylation Patterns	0:35	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein	0:67	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	4	106	theme	S1	517:518	arg1	domain					520:525	the S1 domain	513:525	the S1 domain	513:525	The spike monomer has two subdomains, S1 and S2, and a receptor-binding domain (RBD) within the S1 domain.
34869209	10	107	link	cell-derived	1188:1199	arg1	WA1					1201:1203	the whole cell-derived WA1	1178:1203	the whole cell-derived WA1	1178:1203	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	10	108	theme	local	1257:1261	arg1	N-glycosites					1244:1255	N-glycosites	1244:1255	N-glycosites local to the mutation site	1244:1282	Comparison of the whole cell-derived WA1 and D614G spike proteins revealed that N-glycosites local to the mutation site appeared to be more readily detected, hinting that these sites are more exposed to glycosylation machinery.
34869209	8	109	theme	HEK293-derived	1007:1020	arg1	S1					1022:1023	HEK293-derived S1	1007:1023	HEK293-derived S1	1007:1023	N-glycans identified in HEK293-derived S1 were structurally diverse.
34869209	3	110	theme	critical	376:383	arg1	roles					385:389	critical roles	376:389	critical roles	376:389	Recent studies show that spike protein glycans play critical roles in viral entry and infection.
34869209	0	111	theme	SARS-CoV-2	44:53	arg1	Protein					61:67	the SARS-CoV-2 Spike Protein	40:67	the SARS-CoV-2 Spike Protein	40:67	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	6	112	theme	D614G	792:796	arg1	variant					798:804	a D614G variant	790:804	a D614G variant	790:804	The Vero cell-derived spike from the WA1 strain and a D614G variant was analyzed.
34869209	13	113	theme	O-glycosites	1852:1863	arg1	range					1843:1847	a range	1841:1847	a range of O-glycosites	1841:1863	Concerning O-glycosylation, our analyses revealed that HEK293 recombinant proteins possessed a range of O-glycosites with compositions consistent with Core type 1 and 2 glycans.
34869209	16	114	theme	host	2281:2284	arg1	efficiency					2312:2321	host ACE2 receptor interaction efficiency	2281:2321	host ACE2 receptor interaction efficiency	2281:2321	SARS-CoV-2 spike glycans are associated with host ACE2 receptor interaction efficiency.
34869209	0	115	theme	Protein	61:67	arg1	Patterns					28:35	Site-Specific Glycosylation Patterns	0:35	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein	0:67	Site-Specific Glycosylation Patterns of the SARS-CoV-2 Spike Protein Derived From Recombinant Protein and Viral WA1 and D614G Strains.
34869209	16	116	theme	receptor	2291:2298	arg1	efficiency					2312:2321	host ACE2 receptor interaction efficiency	2281:2321	host ACE2 receptor interaction efficiency	2281:2321	SARS-CoV-2 spike glycans are associated with host ACE2 receptor interaction efficiency.
34869209	15	117	theme	cell	2126:2129	arg1	substrate					2131:2139	cell substrate	2126:2139	cell substrate	2126:2139	Overall, this study reveals that the sample nature and cell substrate used for production of these proteins can have a dramatic impact on the glycosylation profile.
34869209	6	118	theme	WA1	775:777	arg1	strain					779:784	the WA1 strain	771:784	the WA1 strain	771:784	The Vero cell-derived spike from the WA1 strain and a D614G variant was analyzed.
34869209	12	119	link	cell-derived	1674:1685	arg1	S1					1699:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	both CHO- and HEK cell-derived recombinant S1	1656:1700	This stands in stark contrast to glycosylation patterns seen in both CHO- and HEK cell-derived recombinant S1, S2, and the whole spike previously reported.
34869209	11	120	theme	whole	1539:1543	arg1	virus					1545:1549	the Vero E6 cell whole virus	1522:1549	the Vero E6 cell whole virus	1522:1549	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	7	121	theme	spike	824:828	arg1	proteins					830:837	All spike proteins	820:837	All spike proteins	820:837	All spike proteins, S1, and RBDs were analyzed using hydrophilic interaction chromatography (HILIC) and LC-MS/MS on an Orbitrap Eclipse Tribrid mass spectrometer.
34869209	14	122	gly	O-glycosites	1930:1941	arg2	O-glycosites					1930:1941	The O-glycosites	1926:1941	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523,	1926:2004	The O-glycosites shared between the S1 and RBD constructs, sites T323 and T523, were occupied by a similar range of Core 1 and 2 type O-glycans.
34869209	11	123	theme	high-mannose	1570:1581	arg1	glycans					1583:1589	high-mannose glycans	1570:1589	high-mannose glycans	1570:1589	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
34869209	11	124	theme	E6	1531:1532	arg1	virus					1545:1549	the Vero E6 cell whole virus	1522:1549	the Vero E6 cell whole virus	1522:1549	Moreover, recombinant HEK293-derived S1 was occupied almost completely with complex glycan, while both WA1 and D614G derived from the Vero E6 cell whole virus were predominantly high-mannose glycans.
33908012	5	0	theme	fluorescence	812:823	arg1	profile					825:831	the fluorescence profile	808:831	the fluorescence profile	808:831	In the first method (AEX-HILIC/FLR), N-glycans are separated based on their charge and the average charge state can be determined from the fluorescence profile.
33908012	7	1	theme	optimized	1127:1135	arg1	protocol					1137:1144	an optimized protocol	1124:1144	an optimized protocol with fast and high-throughput sample preparation and purification	1124:1210	In addition, in this method, the N-glycans are also separated by type and identified with the hyphenated MS. For both methods, an optimized protocol with fast and high-throughput sample preparation and purification is presented.
33908012	1	2	theme	sialic	184:189	arg1	acids					191:195	sialic acids	184:195	sialic acids	184:195	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	0	3	theme	Relative	11:18	arg1	Quantification					20:33	Relative Quantification	11:33	Relative Quantification	11:33	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	0	4	theme	Oligosaccharides	78:93	arg1	Profiling					0:8	Profiling	0:8	Profiling	0:8	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	0	4	theme	Oligosaccharides	78:93	arg1	Quantification					20:33	Relative Quantification	11:33	Relative Quantification	11:33	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	0	4	theme	Oligosaccharides	78:93	arg1	Identification					40:53	Identification	40:53	Identification	40:53	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	2	5	dep	immunogenicity	323:336	arg1	properties					338:347	properties	338:347	properties	338:347	The presence of these charged monosaccharides is critical for the immunogenicity properties and structural properties of the proteins.
33908012	4	6	theme	different	644:652	arg1	levels					654:659	different levels	644:659	different levels of details	644:670	Two analytical methods developed on released N-glycans are described in this chapter, allowing for the determination of the sialoglycosylation with different levels of details.
33908012	3	7	theme	N-glycans	409:417	arg1	Profiling					392:400	Profiling	392:400	Profiling of the N-glycans and their charge state	392:440	Profiling of the N-glycans and their charge state is a requisite for complete protein characterization.
33908012	4	8	theme	details	664:670	arg1	levels					654:659	different levels	644:659	different levels of details	644:670	Two analytical methods developed on released N-glycans are described in this chapter, allowing for the determination of the sialoglycosylation with different levels of details.
33908012	6	9	theme	sialylation	931:941	arg1	level					943:947	the sialylation level	927:947	the sialylation level	927:947	In the second method (AEX-RP-FLR-MS), N-glycans are also separated based on their charge and the sialylation level is determined based on the fluorescence signal.
33908012	4	10	with	sialoglycosylation	620:637	arg1	levels					654:659	different levels	644:659	different levels of details	644:670	Two analytical methods developed on released N-glycans are described in this chapter, allowing for the determination of the sialoglycosylation with different levels of details.
33908012	4	11	theme	released	532:539	arg1	N-glycans					541:549	released N-glycans	532:549	released N-glycans	532:549	Two analytical methods developed on released N-glycans are described in this chapter, allowing for the determination of the sialoglycosylation with different levels of details.
33908012	5	12	theme	first	680:684	arg1	AEX-HILIC/FLR					694:706	AEX-HILIC/FLR	694:706	AEX-HILIC/FLR	694:706	In the first method (AEX-HILIC/FLR), N-glycans are separated based on their charge and the average charge state can be determined from the fluorescence profile.
33908012	5	12	theme	first	680:684	arg1	method					686:691	the first method	676:691	the first method (AEX-HILIC/FLR)	676:707	In the first method (AEX-HILIC/FLR), N-glycans are separated based on their charge and the average charge state can be determined from the fluorescence profile.
33908012	1	13	gly	glycosylated	222:233	arg1	proteins					247:254	glycosylated therapeutic proteins	222:254	glycosylated therapeutic proteins	222:254	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	6	14	theme	second	841:846	arg1	AEX-RP-FLR-MS					856:868	AEX-RP-FLR-MS	856:868	AEX-RP-FLR-MS	856:868	In the second method (AEX-RP-FLR-MS), N-glycans are also separated based on their charge and the sialylation level is determined based on the fluorescence signal.
33908012	6	14	theme	second	841:846	arg1	method					848:853	the second method	837:853	the second method (AEX-RP-FLR-MS)	837:869	In the second method (AEX-RP-FLR-MS), N-glycans are also separated based on their charge and the sialylation level is determined based on the fluorescence signal.
33908012	7	15	with	protocol	1137:1144	arg1	preparation					1183:1193	fast and high-throughput sample preparation	1151:1193	fast and high-throughput sample preparation	1151:1193	In addition, in this method, the N-glycans are also separated by type and identified with the hyphenated MS. For both methods, an optimized protocol with fast and high-throughput sample preparation and purification is presented.
33908012	7	15	with	protocol	1137:1144	arg1	purification					1199:1210	purification	1199:1210	purification	1199:1210	In addition, in this method, the N-glycans are also separated by type and identified with the hyphenated MS. For both methods, an optimized protocol with fast and high-throughput sample preparation and purification is presented.
33908012	3	16	theme	state	436:440	arg1	Profiling					392:400	Profiling	392:400	Profiling of the N-glycans and their charge state	392:440	Profiling of the N-glycans and their charge state is a requisite for complete protein characterization.
33908012	0	17	with	Derivatization	120:133	arg1	Anthranilamide					152:165	Fluorescent Anthranilamide	140:165	Fluorescent Anthranilamide	140:165	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	3	18	theme	protein	470:476	arg1	characterization					478:493	complete protein characterization	461:493	complete protein characterization	461:493	Profiling of the N-glycans and their charge state is a requisite for complete protein characterization.
33908012	7	19	theme	high-throughput	1160:1174	arg1	preparation					1183:1193	fast and high-throughput sample preparation	1151:1193	fast and high-throughput sample preparation	1151:1193	In addition, in this method, the N-glycans are also separated by type and identified with the hyphenated MS. For both methods, an optimized protocol with fast and high-throughput sample preparation and purification is presented.
33908012	7	20	theme	sample	1176:1181	arg1	preparation					1183:1193	fast and high-throughput sample preparation	1151:1193	fast and high-throughput sample preparation	1151:1193	In addition, in this method, the N-glycans are also separated by type and identified with the hyphenated MS. For both methods, an optimized protocol with fast and high-throughput sample preparation and purification is presented.
33908012	2	21	theme	structural	353:362	arg1	properties					364:373	structural properties	353:373	structural properties	353:373	The presence of these charged monosaccharides is critical for the immunogenicity properties and structural properties of the proteins.
33908012	1	22	theme	glycosylated	222:233	arg1	proteins					247:254	glycosylated therapeutic proteins	222:254	glycosylated therapeutic proteins	222:254	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	3	23	theme	charge	429:434	arg1	state					436:440	their charge state	423:440	their charge state	423:440	Profiling of the N-glycans and their charge state is a requisite for complete protein characterization.
33908012	0	24	theme	Fluorescent	140:150	arg1	Anthranilamide					152:165	Fluorescent Anthranilamide	140:165	Fluorescent Anthranilamide	140:165	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	1	25	theme	acids	191:195	arg1	characteristic					204:217	one characteristic	200:217	one characteristic of glycosylated therapeutic proteins	200:254	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	1	25	theme	acids	191:195	arg1	presence					172:179	The presence	168:179	The presence of sialic acids	168:195	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	1	26	theme	therapeutic	235:245	arg1	proteins					247:254	glycosylated therapeutic proteins	222:254	glycosylated therapeutic proteins	222:254	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	4	27	theme	sialoglycosylation	620:637	arg1	determination					599:611	the determination	595:611	the determination of the sialoglycosylation with different levels of details	595:670	Two analytical methods developed on released N-glycans are described in this chapter, allowing for the determination of the sialoglycosylation with different levels of details.
33908012	5	28	theme	average	764:770	arg1	state					779:783	the average charge state	760:783	the average charge state	760:783	In the first method (AEX-HILIC/FLR), N-glycans are separated based on their charge and the average charge state can be determined from the fluorescence profile.
33908012	4	29	theme	analytical	500:509	arg1	methods					511:517	Two analytical methods	496:517	Two analytical methods developed on released N-glycans	496:549	Two analytical methods developed on released N-glycans are described in this chapter, allowing for the determination of the sialoglycosylation with different levels of details.
33908012	1	30	theme	proteins	247:254	arg1	characteristic					204:217	one characteristic	200:217	one characteristic of glycosylated therapeutic proteins	200:254	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	1	30	theme	proteins	247:254	arg1	presence					172:179	The presence	168:179	The presence of sialic acids	168:195	The presence of sialic acids is one characteristic of glycosylated therapeutic proteins.
33908012	3	31	theme	complete	461:468	arg1	characterization					478:493	complete protein characterization	461:493	complete protein characterization	461:493	Profiling of the N-glycans and their charge state is a requisite for complete protein characterization.
33908012	5	32	theme	charge	772:777	arg1	state					779:783	the average charge state	760:783	the average charge state	760:783	In the first method (AEX-HILIC/FLR), N-glycans are separated based on their charge and the average charge state can be determined from the fluorescence profile.
33908012	6	33	theme	fluorescence	976:987	arg1	signal					989:994	the fluorescence signal	972:994	the fluorescence signal	972:994	In the second method (AEX-RP-FLR-MS), N-glycans are also separated based on their charge and the sialylation level is determined based on the fluorescence signal.
33908012	7	34	theme	fast	1151:1154	arg1	preparation					1183:1193	fast and high-throughput sample preparation	1151:1193	fast and high-throughput sample preparation	1151:1193	In addition, in this method, the N-glycans are also separated by type and identified with the hyphenated MS. For both methods, an optimized protocol with fast and high-throughput sample preparation and purification is presented.
33908012	3	35	dep	N-glycans	409:417	arg1	the					405:407	the	405:407	the	405:407	Profiling of the N-glycans and their charge state is a requisite for complete protein characterization.
33908012	2	36	theme	proteins	382:389	arg1	immunogenicity					323:336	the immunogenicity properties and structural properties	319:373	immunogenicity	323:336	The presence of these charged monosaccharides is critical for the immunogenicity properties and structural properties of the proteins.
33908012	2	36	theme	proteins	382:389	arg1	properties					364:373	structural properties	353:373	structural properties	353:373	The presence of these charged monosaccharides is critical for the immunogenicity properties and structural properties of the proteins.
33908012	7	37	theme	hyphenated	1091:1100	arg1	MS.					1102:1104	the hyphenated MS.	1087:1104	the hyphenated MS. For both methods	1087:1121	In addition, in this method, the N-glycans are also separated by type and identified with the hyphenated MS. For both methods, an optimized protocol with fast and high-throughput sample preparation and purification is presented.
33908012	0	38	theme	N-Linked	69:76	arg1	Oligosaccharides					78:93	Sialylated N-Linked Oligosaccharides	58:93	Sialylated N-Linked Oligosaccharides	58:93	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	2	39	theme	monosaccharides	287:301	arg1	presence					261:268	The presence	257:268	The presence of these charged monosaccharides	257:301	The presence of these charged monosaccharides is critical for the immunogenicity properties and structural properties of the proteins.
33908012	2	39	theme	monosaccharides	287:301	arg1	critical					306:313	critical	306:313	critical	306:313	The presence of these charged monosaccharides is critical for the immunogenicity properties and structural properties of the proteins.
33908012	0	40	theme	Sialylated	58:67	arg1	Oligosaccharides					78:93	Sialylated N-Linked Oligosaccharides	58:93	Sialylated N-Linked Oligosaccharides	58:93	Profiling, Relative Quantification, and Identification of Sialylated N-Linked Oligosaccharides by UPLC-FLR-ESI/MS After Derivatization with Fluorescent Anthranilamide.
33908012	2	41	theme	charged	279:285	arg1	monosaccharides					287:301	these charged monosaccharides	273:301	these charged monosaccharides	273:301	The presence of these charged monosaccharides is critical for the immunogenicity properties and structural properties of the proteins.
31932305	10	0	theme	E6	1465:1466	arg1	protein					1468:1474	E6 protein	1465:1474	E6 protein	1465:1474	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	1	1	theme	site-associated	267:281	arg1	gene					283:286	glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6	212:288	glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6)	212:302	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	6	2	from	N-glycans	1079:1087	arg1	synthesis					1038:1046	synthesis	1038:1046	synthesis of poly-LacNAc on paucimannose N-glycans	1038:1087	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	10	3	theme	GPI	1484:1486	arg1	aa					1496:1497	aa 4-7	1496:1501	aa 4-7	1496:1501	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	10	3	theme	GPI	1484:1486	arg1	ω-site					1488:1493	the GPI ω-site	1480:1493	the GPI ω-site (aa 4-7)	1480:1502	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	0	4	theme	Steric	0:5	arg1	constraints					7:17	Steric constraints	0:17	Steric constraints	0:17	Steric constraints control processing of glycosylphosphatidylinositol anchors in Trypanosoma brucei.
31932305	1	5	theme	Trypanosoma	165:175	arg1	brucei					177:182	Trypanosoma brucei	165:182	Trypanosoma brucei	165:182	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	10	6	theme	structures	1644:1653	arg1	addition					1625:1632	the addition	1621:1632	the addition of LacNAc structures	1621:1653	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	9	7	with	consistent	1387:1396	arg1	addition					1415:1422	α-galactose addition	1403:1422	α-galactose addition	1403:1422	Minor GPI processing was also observed, consistent with α-galactose addition.
31932305	5	8	theme	GPI	884:886	arg1	processing					888:897	GPI processing	884:897	GPI processing	884:897	Using pulse-chase radiolabeling, peptide-N-glycosidase F treatment, lectin pulldowns, and exoglycosidase treatment, we have now investigated TfR N-glycan and GPI processing.
31932305	8	9	theme	previous	1318:1325	arg1	studies					1338:1344	previous structural studies	1318:1344	previous structural studies	1318:1344	These results contradict previous structural studies.
31932305	11	10	theme	insect-stage	1850:1861	arg1	trypanosomes					1863:1874	insect-stage trypanosomes	1850:1874	insect-stage trypanosomes	1850:1874	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	11	11	from	present	1839:1845	arg1	trypanosomes					1863:1874	insect-stage trypanosomes	1850:1874	insect-stage trypanosomes	1850:1874	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	4	12	theme	transport-dependent	616:634	arg1	increases					636:644	transport-dependent increases	616:644	transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum	616:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	10	13	theme	identical	1669:1677	arg1	assays					1679:1684	identical assays	1669:1684	identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter	1669:1740	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	10	14	gly	non-N-glycosylated	1701:1718	arg1	reporter					1733:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	10	14	gly	non-N-glycosylated	1701:1718	arg1	BiPNHP					1691:1696	BiPNHP	1691:1696	BiPNHP	1691:1696	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	11	15	theme	steric	1885:1890	arg1	constraints					1892:1902	steric constraints	1885:1902	steric constraints	1885:1902	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	11	15	theme	steric	1885:1890	arg1	expression					1924:1933	not stage-specific expression	1905:1933	not stage-specific expression of glycosyltransferases	1905:1957	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	1	16	theme	bloodstream	139:149	arg1	BSF					157:159	BSF	157:159	BSF	157:159	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	1	16	theme	bloodstream	139:149	arg1	form					151:154	the bloodstream form	135:154	the bloodstream form (BSF) of Trypanosoma brucei	135:182	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	7	17	theme	secretory	1269:1277	arg1	polypeptides					1279:1290	nascent secretory polypeptides	1261:1290	nascent secretory polypeptides	1261:1290	This processing was lost after exoglycosidase treatment and after RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides.
31932305	11	18	theme	stage-specific	1909:1922	arg1	constraints					1892:1902	steric constraints	1885:1902	steric constraints	1885:1902	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	11	18	theme	stage-specific	1909:1922	arg1	expression					1924:1933	not stage-specific expression	1905:1933	not stage-specific expression of glycosyltransferases	1905:1957	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	9	19	theme	GPI	1353:1355	arg1	processing					1357:1366	Minor GPI processing	1347:1366	Minor GPI processing	1347:1366	Minor GPI processing was also observed, consistent with α-galactose addition.
31932305	7	20	theme	paucimannose	1234:1245	arg1	structures					1247:1256	paucimannose structures	1234:1256	paucimannose structures	1234:1256	This processing was lost after exoglycosidase treatment and after RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides.
31932305	6	21	theme	cristagalli	984:994	arg1	lectin					996:1001	Erythrina cristagalli lectin	974:1001	Erythrina cristagalli lectin (ECL, terminal LacNAc)	974:1024	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	10	22	theme	extensive	1516:1524	arg1	processing					1545:1554	extensive post-translational processing	1516:1554	extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures	1516:1653	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	3	23	theme	GPI	435:437	arg1	anchor					439:444	Its GPI anchor	431:444	Its GPI anchor	431:444	Its GPI anchor is modified by the addition of 4-6 α-galactose residues.
31932305	0	24	theme	glycosylphosphatidylinositol	41:68	arg1	anchors					70:76	glycosylphosphatidylinositol anchors	41:76	glycosylphosphatidylinositol anchors	41:76	Steric constraints control processing of glycosylphosphatidylinositol anchors in Trypanosoma brucei.
31932305	6	25	theme	paucimannose	1066:1077	arg1	N-glycans					1079:1087	paucimannose N-glycans	1066:1087	paucimannose N-glycans	1066:1087	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	5	26	theme	exoglycosidase	816:829	arg1	treatment					831:839	exoglycosidase treatment	816:839	exoglycosidase treatment	816:839	Using pulse-chase radiolabeling, peptide-N-glycosidase F treatment, lectin pulldowns, and exoglycosidase treatment, we have now investigated TfR N-glycan and GPI processing.
31932305	6	27	theme	poly-LacNAc	1051:1061	arg1	synthesis					1038:1046	synthesis	1038:1046	synthesis of poly-LacNAc on paucimannose N-glycans	1038:1087	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	7	28	theme	TbSTT3A	1180:1186	arg1	silencing					1167:1175	RNAi-based silencing	1156:1175	RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides	1156:1290	This processing was lost after exoglycosidase treatment and after RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides.
31932305	9	29	theme	α-galactose	1403:1413	arg1	addition					1415:1422	α-galactose addition	1403:1422	α-galactose addition	1403:1422	Minor GPI processing was also observed, consistent with α-galactose addition.
31932305	4	30	theme	specific	533:540	arg1	TL					528:529	TL	528:529	TL	528:529	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	4	30	theme	specific	533:540	arg1	lectin					520:525	tomato lectin	513:525	tomato lectin (TL)	513:530	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	11	31	theme	BSF	1760:1762	arg1	trypanosomes					1764:1775	BSF trypanosomes	1760:1775	BSF trypanosomes	1760:1775	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	10	32	theme	GPI-anchored	1720:1731	arg1	reporter					1733:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	10	32	theme	GPI-anchored	1720:1731	arg1	BiPNHP					1691:1696	BiPNHP	1691:1696	BiPNHP	1691:1696	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	5	33	theme	lectin	794:799	arg1	pulldowns					801:809	lectin pulldowns	794:809	lectin pulldowns	794:809	Using pulse-chase radiolabeling, peptide-N-glycosidase F treatment, lectin pulldowns, and exoglycosidase treatment, we have now investigated TfR N-glycan and GPI processing.
31932305	4	34	theme	tomato	513:518	arg1	TL					528:529	TL	528:529	TL	528:529	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	4	34	theme	tomato	513:518	arg1	lectin					520:525	tomato lectin	513:525	tomato lectin (TL)	513:530	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	5	35	theme	peptide-N-glycosidase	759:779	arg1	F					781:781	peptide-N-glycosidase F	759:781	peptide-N-glycosidase F treatment	759:791	Using pulse-chase radiolabeling, peptide-N-glycosidase F treatment, lectin pulldowns, and exoglycosidase treatment, we have now investigated TfR N-glycan and GPI processing.
31932305	0	36	theme	anchors	70:76	arg1	processing					27:36	processing	27:36	processing of glycosylphosphatidylinositol anchors in Trypanosoma brucei	27:98	Steric constraints control processing of glycosylphosphatidylinositol anchors in Trypanosoma brucei.
31932305	1	37	theme	soluble	308:314	arg1	ESAG7					316:320	soluble ESAG7	308:320	soluble ESAG7	308:320	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	0	38	from	processing	27:36	arg1	brucei					93:98	Trypanosoma brucei	81:98	Trypanosoma brucei	81:98	Steric constraints control processing of glycosylphosphatidylinositol anchors in Trypanosoma brucei.
31932305	10	39	theme	anchor	1567:1572	arg1	processing					1545:1554	extensive post-translational processing	1516:1554	extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures	1516:1653	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	2	40	theme	Mature	323:328	arg1	E6					330:331	Mature E6	323:331	Mature E6	323:331	Mature E6 has five N-glycans, consisting of three oligomannose and two unprocessed paucimannose structures.
31932305	11	41	theme	GPI	1969:1971	arg1	processing					1973:1982	GPI processing	1969:1982	GPI processing	1969:1982	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	10	42	with	assays	1679:1684	arg1	reporter					1733:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	10	42	with	assays	1679:1684	arg1	BiPNHP					1691:1696	BiPNHP	1691:1696	BiPNHP	1691:1696	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	7	43	theme	exoglycosidase	1121:1134	arg1	treatment					1136:1144	exoglycosidase treatment	1121:1144	exoglycosidase treatment	1121:1144	This processing was lost after exoglycosidase treatment and after RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides.
31932305	3	44	theme	residues	493:500	arg1	addition					465:472	the addition	461:472	the addition of 4-6 α-galactose residues	461:500	Its GPI anchor is modified by the addition of 4-6 α-galactose residues.
31932305	1	45	theme	expression	256:265	arg1	gene					283:286	glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6	212:288	glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6)	212:302	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	4	46	theme	N-acetyllactosamine	546:564	arg1	repeats					575:581	N-acetyllactosamine (LacNAc) repeats	546:581	N-acetyllactosamine (LacNAc) repeats	546:581	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	6	47	from	poly-LacNAc	1051:1061	arg1	N-glycans					1079:1087	paucimannose N-glycans	1066:1087	paucimannose N-glycans	1066:1087	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	4	48	theme	LacNAc	567:572	arg1	repeats					575:581	N-acetyllactosamine (LacNAc) repeats	546:581	N-acetyllactosamine (LacNAc) repeats	546:581	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	5	49	theme	TfR	867:869	arg1	N-glycan					871:878	TfR N-glycan	867:878	TfR N-glycan	867:878	Using pulse-chase radiolabeling, peptide-N-glycosidase F treatment, lectin pulldowns, and exoglycosidase treatment, we have now investigated TfR N-glycan and GPI processing.
31932305	11	50	from	trypanosomes	1863:1874	arg1	present					1839:1845	present	1839:1845	present	1839:1845	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	4	51	with	consistent	657:666	arg1	processing					685:694	post-glycan processing	673:694	post-glycan processing in the endoplasmic reticulum	673:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	4	52	from	increases	636:644	arg1	size					652:655	E6 size	649:655	E6 size consistent with post-glycan processing in the endoplasmic reticulum	649:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	1	53	theme	brucei	177:182	arg1	BSF					157:159	BSF	157:159	BSF	157:159	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	1	53	theme	brucei	177:182	arg1	form					151:154	the bloodstream form	135:154	the bloodstream form (BSF) of Trypanosoma brucei	135:182	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	6	54	theme	Erythrina	974:982	arg1	lectin					996:1001	Erythrina cristagalli lectin	974:1001	Erythrina cristagalli lectin (ECL, terminal LacNAc)	974:1024	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	4	55	theme	E6	649:650	arg1	size					652:655	E6 size	649:655	E6 size consistent with post-glycan processing in the endoplasmic reticulum	649:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	10	56	theme	LacNAc	1637:1642	arg1	structures					1644:1653	LacNAc structures	1637:1653	LacNAc structures	1637:1653	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	6	57	from	synthesis	1038:1046	arg1	N-glycans					1079:1087	paucimannose N-glycans	1066:1087	paucimannose N-glycans	1066:1087	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	11	58	theme	glycosyltransferases	1938:1957	arg1	constraints					1892:1902	steric constraints	1885:1902	steric constraints	1885:1902	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	11	58	theme	glycosyltransferases	1938:1957	arg1	expression					1924:1933	not stage-specific expression	1905:1933	not stage-specific expression of glycosyltransferases	1905:1957	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	8	59	theme	structural	1327:1336	arg1	studies					1338:1344	previous structural studies	1318:1344	previous structural studies	1318:1344	These results contradict previous structural studies.
31932305	11	60	attach	present	1839:1845	arg2	those					1833:1837	those	1833:1837	those	1833:1837	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	11	60	attach	present	1839:1845	arg1	trypanosomes					1863:1874	insect-stage trypanosomes	1850:1874	insect-stage trypanosomes	1850:1874	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	3	61	mod	modified	449:456	arg3	addition					465:472	the addition	461:472	the addition of 4-6 α-galactose residues	461:500	Its GPI anchor is modified by the addition of 4-6 α-galactose residues.
31932305	3	61	mod	modified	449:456	arg1	anchor					439:444	Its GPI anchor	431:444	Its GPI anchor	431:444	Its GPI anchor is modified by the addition of 4-6 α-galactose residues.
31932305	1	62	dep	gene	283:286	arg1	E6					300:301	E6	300:301	E6	300:301	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	1	62	dep	gene	283:286	arg1	ESAG6					291:295	ESAG6	291:295	ESAG6	291:295	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	4	63	theme	endoplasmic	703:713	arg1	reticulum					715:723	the endoplasmic reticulum	699:723	the endoplasmic reticulum	699:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	11	64	theme	reminiscent	1818:1828	arg1	structures					1807:1816	structures	1807:1816	structures reminiscent of those present in insect-stage trypanosomes	1807:1874	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	7	65	theme	nascent	1261:1267	arg1	polypeptides					1279:1290	nascent secretory polypeptides	1261:1290	nascent secretory polypeptides	1261:1290	This processing was lost after exoglycosidase treatment and after RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides.
31932305	1	66	theme	form	151:154	arg1	receptor					117:124	The transferrin receptor	101:124	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei	101:182	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	1	66	theme	form	151:154	arg1	TfR					127:129	TfR	127:129	TfR	127:129	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	1	66	theme	form	151:154	arg1	heterodimer					189:199	a heterodimer	187:199	a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7	187:320	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	6	67	theme	terminal	1009:1016	arg1	ECL					1004:1006	ECL	1004:1006	ECL	1004:1006	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	6	67	theme	terminal	1009:1016	arg1	LacNAc					1018:1023	terminal LacNAc	1009:1023	terminal LacNAc	1009:1023	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	6	68	dep	lectin	996:1001	arg1	ECL					1004:1006	ECL	1004:1006	ECL	1004:1006	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	6	68	dep	lectin	996:1001	arg1	LacNAc					1018:1023	terminal LacNAc	1009:1023	terminal LacNAc	1009:1023	E6 increased ∼5 kDa during maturation, becoming reactive with both TL and Erythrina cristagalli lectin (ECL, terminal LacNAc), indicating synthesis of poly-LacNAc on paucimannose N-glycans.
31932305	4	69	theme	consistent	657:666	arg1	size					652:655	E6 size	649:655	E6 size consistent with post-glycan processing in the endoplasmic reticulum	649:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	5	70	theme	F	781:781	arg1	treatment					783:791	peptide-N-glycosidase F treatment	759:791	peptide-N-glycosidase F treatment	759:791	Using pulse-chase radiolabeling, peptide-N-glycosidase F treatment, lectin pulldowns, and exoglycosidase treatment, we have now investigated TfR N-glycan and GPI processing.
31932305	9	71	theme	Minor	1347:1351	arg1	processing					1357:1366	Minor GPI processing	1347:1366	Minor GPI processing	1347:1366	Minor GPI processing was also observed, consistent with α-galactose addition.
31932305	4	72	theme	post-glycan	673:683	arg1	processing					685:694	post-glycan processing	673:694	post-glycan processing in the endoplasmic reticulum	673:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	2	73	contain	has	333:335	arg1	E6					330:331	Mature E6	323:331	Mature E6	323:331	Mature E6 has five N-glycans, consisting of three oligomannose and two unprocessed paucimannose structures.
31932305	2	73	contain	has	333:335	arg2	N-glycans					342:350	five N-glycans	337:350	five N-glycans	337:350	Mature E6 has five N-glycans, consisting of three oligomannose and two unprocessed paucimannose structures.
31932305	11	74	theme	those	1833:1837	arg1	reminiscent					1818:1828	reminiscent	1818:1828	reminiscent	1818:1828	We conclude that BSF trypanosomes can modify GPIs by generating structures reminiscent of those present in insect-stage trypanosomes and that steric constraints, not stage-specific expression of glycosyltransferases, regulate GPI processing.
31932305	5	75	theme	pulse-chase	732:742	arg1	radiolabeling					744:756	pulse-chase radiolabeling	732:756	pulse-chase radiolabeling	732:756	Using pulse-chase radiolabeling, peptide-N-glycosidase F treatment, lectin pulldowns, and exoglycosidase treatment, we have now investigated TfR N-glycan and GPI processing.
31932305	2	76	theme	unprocessed	394:404	arg1	structures					419:428	three oligomannose and two unprocessed paucimannose structures	367:428	structures	419:428	Mature E6 has five N-glycans, consisting of three oligomannose and two unprocessed paucimannose structures.
31932305	10	77	dep	resulted	1504:1511	arg1	confirmed					1656:1664	confirmed	1656:1664	confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter	1656:1740	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	1	78	theme	transferrin	105:115	arg1	receptor					117:124	The transferrin receptor	101:124	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei	101:182	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	1	78	theme	transferrin	105:115	arg1	TfR					127:129	TfR	127:129	TfR	127:129	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	1	78	theme	transferrin	105:115	arg1	heterodimer					189:199	a heterodimer	187:199	a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7	187:320	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
31932305	2	79	theme	paucimannose	406:417	arg1	structures					419:428	three oligomannose and two unprocessed paucimannose structures	367:428	structures	419:428	Mature E6 has five N-glycans, consisting of three oligomannose and two unprocessed paucimannose structures.
31932305	7	80	theme	RNAi-based	1156:1165	arg1	silencing					1167:1175	RNAi-based silencing	1156:1175	RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides	1156:1290	This processing was lost after exoglycosidase treatment and after RNAi-based silencing of TbSTT3A, the oligosaccharyltransferase that transfers paucimannose structures to nascent secretory polypeptides.
31932305	10	81	theme	post-translational	1526:1543	arg1	processing					1545:1554	extensive post-translational processing	1516:1554	extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures	1516:1653	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	10	82	theme	non-N-glycosylated	1701:1718	arg1	reporter					1733:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	a non-N-glycosylated GPI-anchored reporter	1699:1740	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	10	82	theme	non-N-glycosylated	1701:1718	arg1	BiPNHP					1691:1696	BiPNHP	1691:1696	BiPNHP	1691:1696	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	0	83	theme	Trypanosoma	81:91	arg1	brucei					93:98	Trypanosoma brucei	81:98	Trypanosoma brucei	81:98	Steric constraints control processing of glycosylphosphatidylinositol anchors in Trypanosoma brucei.
31932305	3	84	theme	α-galactose	481:491	arg1	residues					493:500	4-6 α-galactose residues	477:500	4-6 α-galactose residues	477:500	Its GPI anchor is modified by the addition of 4-6 α-galactose residues.
31932305	10	85	theme	GPI	1563:1565	arg1	anchor					1567:1572	the GPI anchor	1559:1572	the GPI anchor	1559:1572	However, increasing the spacing between E6 protein and the GPI ω-site (aa 4-7) resulted in extensive post-translational processing of the GPI anchor to a form that was TL/ECL-reactive, suggesting the addition of LacNAc structures, confirmed by identical assays with BiPNHP, a non-N-glycosylated GPI-anchored reporter.
31932305	4	86	theme	previous	588:595	arg1	studies					597:603	previous studies	588:603	previous studies	588:603	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	4	87	from	processing	685:694	arg1	reticulum					715:723	the endoplasmic reticulum	699:723	the endoplasmic reticulum	699:723	TfR binds tomato lectin (TL), specific for N-acetyllactosamine (LacNAc) repeats, and previous studies have shown transport-dependent increases in E6 size consistent with post-glycan processing in the endoplasmic reticulum.
31932305	1	88	theme	-anchored	246:254	arg1	gene					283:286	glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6	212:288	glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6)	212:302	The transferrin receptor (TfR) of the bloodstream form (BSF) of Trypanosoma brucei is a heterodimer comprising glycosylphosphatidylinositol (GPI)-anchored expression site-associated gene 6 (ESAG6 or E6) and soluble ESAG7.
32441515	4	0	theme	crucial	599:605	arg1	energy					582:587	Collision energy	572:587	Collision energy (CE)	572:592	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	4	0	theme	crucial	599:605	arg1	parameter					618:626	a crucial instrument parameter	597:626	a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation	597:779	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	7	1	theme	arm	1199:1201	arg1	motifs					1213:1218	outer arm structure motifs	1193:1218	outer arm structure motifs with recognized biological functions	1193:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	2	2	theme	3D	408:409	arg1	structure					411:419	the 3D structure	404:419	the 3D structure of proteins	404:431	The glycans attached to proteins represent an important determinant of the protein interaction-specificity and maintain the 3D structure of proteins.
32441515	4	3	theme	different	691:699	arg1	linkages					701:708	different linkages	691:708	different linkages of glycan units	691:724	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	9	4	theme	identification	1566:1579	arg1	confidence					1539:1548	confidence	1539:1548	confidence of glycopeptide identification and structural resolution	1539:1605	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	9	5	theme	structural	1585:1594	arg1	resolution					1596:1605	structural resolution	1585:1605	structural resolution	1585:1605	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	9	6	theme	glycopeptide	1553:1564	arg1	identification					1566:1579	glycopeptide identification	1553:1579	glycopeptide identification	1553:1579	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	3	7	theme	structure	541:549	arg1	studies					512:518	the current studies	500:518	the current studies of glycoproteins and structure of their glycoforms	500:569	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	5	8	theme	structure-specific	881:898	arg1	glycoforms					900:909	site- and structure-specific glycoforms	871:909	site- and structure-specific glycoforms of proteins	871:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	8	9	theme	optimized	1300:1308	arg1	conditions					1324:1333	optimized low CE (soft) conditions	1300:1333	optimized low CE (soft) conditions	1300:1333	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	6	10	theme	intact	1007:1012	arg1	glycopeptides					1014:1026	intact glycopeptides	1007:1026	intact glycopeptides	1007:1026	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	9	11	gly	glycopeptide	1553:1564	arg2	glycopeptide					1553:1564	glycopeptide	1553:1564	glycopeptide	1553:1564	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	8	12	theme	structural	1355:1364	arg1	information					1366:1376	additional structural information	1344:1376	additional structural information including features specific to the chitobiose core	1344:1427	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	7	13	theme	oxonium	1127:1133	arg1	ions					1135:1138	Structure- and CE-specific oxonium ions	1100:1138	Structure- and CE-specific oxonium ions	1100:1138	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	9	14	theme	additional	1620:1629	arg1	information					1631:1641	additional information	1620:1641	additional information	1620:1641	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	8	15	theme	CE	1314:1315	arg1	conditions					1324:1333	optimized low CE (soft) conditions	1300:1333	optimized low CE (soft) conditions	1300:1333	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	6	16	theme	specific	979:986	arg1	linkages					995:1002	specific glycan linkages	979:1002	specific glycan linkages on intact glycopeptides	979:1026	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	8	17	theme	specific	1397:1404	arg1	features					1388:1395	features	1388:1395	features specific to the chitobiose core	1388:1427	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	9	18	theme	established	1650:1660	arg1	algorithms					1682:1691	the established glycopeptide-search algorithms	1646:1691	the established glycopeptide-search algorithms	1646:1691	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	6	19	theme	mass	1072:1075	arg1	signals					1091:1097	structure-specific mass spectrometric signals	1053:1097	structure-specific mass spectrometric signals	1053:1097	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	4	20	theme	units	720:724	arg1	linkages					701:708	different linkages	691:708	different linkages of glycan units	691:724	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	2	21	attach	attached	296:303	arg2	glycans					288:294	The glycans	284:294	The glycans attached to proteins	284:315	The glycans attached to proteins represent an important determinant of the protein interaction-specificity and maintain the 3D structure of proteins.
32441515	2	21	attach	attached	296:303	arg1	proteins					308:315	proteins	308:315	proteins	308:315	The glycans attached to proteins represent an important determinant of the protein interaction-specificity and maintain the 3D structure of proteins.
32441515	4	22	theme	different	731:739	arg1	stabilities					741:751	different stabilities	731:751	different stabilities	731:751	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	5	23	theme	CE	812:813	arg1	modulation					815:824	CE modulation	812:824	CE modulation	812:824	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	1	24	theme	protein	203:209	arg1	folding					211:217	protein folding	203:217	protein folding	203:217	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	25	theme	many	167:170	arg1	responses					273:281	immune responses	266:281	immune responses	266:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	25	theme	many	167:170	arg1	processes					183:191	many biological processes	167:191	many biological processes including protein folding, structure stability, receptor activation, and immune responses	167:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	25	theme	many	167:170	arg1	folding					211:217	protein folding	203:217	protein folding	203:217	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	25	theme	many	167:170	arg1	stability					230:238	structure stability	220:238	structure stability	220:238	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	25	theme	many	167:170	arg1	activation					250:259	receptor activation	241:259	receptor activation	241:259	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	0	26	theme	Structure-Specific	38:55	arg1	Analysis					73:80	Structure-Specific Glycoproteomics Analysis	38:80	Structure-Specific Glycoproteomics Analysis	38:80	Low Collision Energy Fragmentation in Structure-Specific Glycoproteomics Analysis.
32441515	3	27	gly	glycoproteins	523:535	arg1	glycoproteins					523:535	glycoproteins	523:535	glycoproteins	523:535	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	0	28	theme	Low	0:2	arg1	Energy					14:19	Low Collision Energy	0:19	Low Collision Energy	0:19	Low Collision Energy Fragmentation in Structure-Specific Glycoproteomics Analysis.
32441515	1	29	theme	post-translational	108:125	arg1	modification					127:138	a major post-translational modification	100:138	a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses	100:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	29	theme	post-translational	108:125	arg1	Glycosylation					83:95	Glycosylation	83:95	Glycosylation	83:95	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	8	30	dep	CE	1314:1315	arg1	soft					1318:1321	soft	1318:1321	soft	1318:1321	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	5	31	theme	site-	871:875	arg1	glycoforms					900:909	site- and structure-specific glycoforms	871:909	site- and structure-specific glycoforms of proteins	871:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	6	32	theme	CE	930:931	arg1	modulation					933:942	CE modulation	930:942	CE modulation	930:942	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	9	33	theme	glycopeptide-search	1662:1680	arg1	algorithms					1682:1691	the established glycopeptide-search algorithms	1646:1691	the established glycopeptide-search algorithms	1646:1691	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	3	34	theme	tools	486:490	arg1	tools					486:490	the most efficient tools	467:490	the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms	467:569	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	3	34	theme	tools	486:490	arg1	one					460:462	one	460:462	one	460:462	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	7	35	theme	recognized	1225:1234	arg1	functions					1247:1255	recognized biological functions	1225:1255	recognized biological functions	1225:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	9	36	theme	multiple	1450:1457	arg1	fragmentation					1462:1474	multiple CE fragmentation	1450:1474	multiple CE fragmentation without merging spectral information	1450:1511	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	0	37	theme	Glycoproteomics	57:71	arg1	Analysis					73:80	Structure-Specific Glycoproteomics Analysis	38:80	Structure-Specific Glycoproteomics Analysis	38:80	Low Collision Energy Fragmentation in Structure-Specific Glycoproteomics Analysis.
32441515	9	38	theme	fragmentation	1462:1474	arg1	methodology					1435:1445	This methodology	1430:1445	This methodology of multiple CE fragmentation without merging spectral information	1430:1511	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	4	39	theme	Collision	572:580	arg1	parameter					618:626	a crucial instrument parameter	597:626	a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation	597:779	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	4	39	theme	Collision	572:580	arg1	CE					590:591	CE	590:591	CE	590:591	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	4	39	theme	Collision	572:580	arg1	energy					582:587	Collision energy	572:587	Collision energy (CE)	572:592	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	3	40	theme	current	504:510	arg1	studies					512:518	the current studies	500:518	the current studies of glycoproteins and structure of their glycoforms	500:569	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	9	41	theme	merging	1484:1490	arg1	information					1501:1511	merging spectral information	1484:1511	merging spectral information	1484:1511	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	2	42	theme	proteins	424:431	arg1	structure					411:419	the 3D structure	404:419	the 3D structure of proteins	404:431	The glycans attached to proteins represent an important determinant of the protein interaction-specificity and maintain the 3D structure of proteins.
32441515	7	43	theme	structure	1203:1211	arg1	motifs					1213:1218	outer arm structure motifs	1193:1218	outer arm structure motifs with recognized biological functions	1193:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	7	44	theme	outer	1193:1197	arg1	motifs					1213:1218	outer arm structure motifs	1193:1218	outer arm structure motifs with recognized biological functions	1193:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	2	45	theme	important	330:338	arg1	determinant					340:350	an important determinant	327:350	an important determinant of the protein interaction-specificity	327:389	The glycans attached to proteins represent an important determinant of the protein interaction-specificity and maintain the 3D structure of proteins.
32441515	7	46	with	motifs	1213:1218	arg1	functions					1247:1255	recognized biological functions	1225:1255	recognized biological functions	1225:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	4	47	theme	instrument	607:616	arg1	energy					582:587	Collision energy	572:587	Collision energy (CE)	572:592	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	4	47	theme	instrument	607:616	arg1	parameter					618:626	a crucial instrument parameter	597:626	a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation	597:779	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	3	48	theme	glycoforms	560:569	arg1	structure					541:549	structure	541:549	structure of their glycoforms	541:569	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	3	48	theme	glycoforms	560:569	arg1	glycoproteins					523:535	glycoproteins	523:535	glycoproteins	523:535	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	5	49	theme	proteins	914:921	arg1	glycoforms					900:909	site- and structure-specific glycoforms	871:909	site- and structure-specific glycoforms of proteins	871:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	7	50	theme	motifs	1213:1218	arg1	resolution					1179:1188	the resolution	1175:1188	the resolution of outer arm structure motifs with recognized biological functions	1175:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	7	51	theme	sufficient	1148:1157	arg1	information					1159:1169	sufficient information	1148:1169	sufficient information for the resolution of outer arm structure motifs with recognized biological functions	1148:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	2	52	theme	protein	359:365	arg1	interaction-specificity					367:389	the protein interaction-specificity	355:389	the protein interaction-specificity	355:389	The glycans attached to proteins represent an important determinant of the protein interaction-specificity and maintain the 3D structure of proteins.
32441515	1	53	theme	structure	220:228	arg1	stability					230:238	structure stability	220:238	structure stability	220:238	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	8	54	theme	complementary	1262:1274	arg1	Y-ions					1276:1281	The complementary Y-ions	1258:1281	The complementary Y-ions	1258:1281	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	5	55	gly	glycoforms	900:909	arg1	proteins					914:921	proteins	914:921	proteins	914:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	6	56	gly	glycopeptides	1014:1026	arg2	glycopeptides					1014:1026	intact glycopeptides	1007:1026	intact glycopeptides	1007:1026	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	9	57	theme	resolution	1596:1605	arg1	confidence					1539:1548	confidence	1539:1548	confidence of glycopeptide identification and structural resolution	1539:1605	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	7	58	theme	CE-specific	1115:1125	arg1	ions					1135:1138	Structure- and CE-specific oxonium ions	1100:1138	Structure- and CE-specific oxonium ions	1100:1138	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	5	59	theme	glycoforms	900:909	arg1	analysis					859:866	qualitative and quantitative analysis	830:866	qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins	830:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	4	60	theme	structural	661:670	arg1	resolution					672:681	structural resolution	661:681	structural resolution	661:681	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	7	61	theme	Structure-	1100:1109	arg1	ions					1135:1138	Structure- and CE-specific oxonium ions	1100:1138	Structure- and CE-specific oxonium ions	1100:1138	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	1	62	theme	proteins	143:150	arg1	modification					127:138	a major post-translational modification	100:138	a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses	100:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	62	theme	proteins	143:150	arg1	Glycosylation					83:95	Glycosylation	83:95	Glycosylation	83:95	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	8	63	theme	low	1310:1312	arg1	CE					1314:1315	low CE	1310:1315	optimized low CE (soft) conditions	1300:1333	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	6	64	theme	glycan	988:993	arg1	linkages					995:1002	specific glycan linkages	979:1002	specific glycan linkages on intact glycopeptides	979:1026	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	6	65	theme	spectrometric	1077:1089	arg1	signals					1091:1097	structure-specific mass spectrometric signals	1053:1097	structure-specific mass spectrometric signals	1053:1097	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	4	66	theme	CID/HCD	759:765	arg1	fragmentation					767:779	CID/HCD fragmentation	759:779	CID/HCD fragmentation	759:779	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	1	67	theme	biological	172:181	arg1	responses					273:281	immune responses	266:281	immune responses	266:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	67	theme	biological	172:181	arg1	processes					183:191	many biological processes	167:191	many biological processes including protein folding, structure stability, receptor activation, and immune responses	167:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	67	theme	biological	172:181	arg1	folding					211:217	protein folding	203:217	protein folding	203:217	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	67	theme	biological	172:181	arg1	stability					230:238	structure stability	220:238	structure stability	220:238	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	67	theme	biological	172:181	arg1	activation					250:259	receptor activation	241:259	receptor activation	241:259	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	6	68	theme	structure-specific	1053:1070	arg1	signals					1091:1097	structure-specific mass spectrometric signals	1053:1097	structure-specific mass spectrometric signals	1053:1097	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	0	69	from	Fragmentation	21:33	arg1	Analysis					73:80	Structure-Specific Glycoproteomics Analysis	38:80	Structure-Specific Glycoproteomics Analysis	38:80	Low Collision Energy Fragmentation in Structure-Specific Glycoproteomics Analysis.
32441515	4	70	theme	glycan	713:718	arg1	units					720:724	glycan units	713:724	glycan units	713:724	Collision energy (CE) is a crucial instrument parameter that can be exploited to improve structural resolution because different linkages of glycan units show different stabilities under CID/HCD fragmentation.
32441515	8	71	theme	chitobiose	1413:1422	arg1	core					1424:1427	the chitobiose core	1409:1427	the chitobiose core	1409:1427	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	1	72	theme	receptor	241:248	arg1	activation					250:259	receptor activation	241:259	receptor activation	241:259	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	9	73	theme	spectral	1492:1499	arg1	information					1501:1511	merging spectral information	1484:1511	merging spectral information	1484:1511	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	3	74	theme	efficient	476:484	arg1	tools					486:490	the most efficient tools	467:490	the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms	467:569	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	5	75	theme	quantitative	846:857	arg1	analysis					859:866	qualitative and quantitative analysis	830:866	qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins	830:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	1	76	theme	major	102:106	arg1	modification					127:138	a major post-translational modification	100:138	a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses	100:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	1	76	theme	major	102:106	arg1	Glycosylation					83:95	Glycosylation	83:95	Glycosylation	83:95	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	7	77	theme	biological	1236:1245	arg1	functions					1247:1255	recognized biological functions	1225:1255	recognized biological functions	1225:1255	Structure- and CE-specific oxonium ions provide sufficient information for the resolution of outer arm structure motifs with recognized biological functions.
32441515	3	78	theme	Mass	434:437	arg1	spectrometry					439:450	Mass spectrometry	434:450	Mass spectrometry (MS)	434:455	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	3	78	theme	Mass	434:437	arg1	MS					453:454	MS	453:454	MS	453:454	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	5	79	theme	modulation	815:824	arg1	utility					801:807	the utility	797:807	the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins	797:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	5	80	theme	qualitative	830:840	arg1	analysis					859:866	qualitative and quantitative analysis	830:866	qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins	830:921	Here we report the utility of CE modulation for qualitative and quantitative analysis of site- and structure-specific glycoforms of proteins.
32441515	9	81	theme	CE	1459:1460	arg1	fragmentation					1462:1474	multiple CE fragmentation	1450:1474	multiple CE fragmentation without merging spectral information	1450:1511	This methodology of multiple CE fragmentation without merging spectral information can significantly improve confidence of glycopeptide identification and structural resolution by providing additional information to the established glycopeptide-search algorithms and tools.
32441515	3	82	theme	glycoproteins	523:535	arg1	studies					512:518	the current studies	500:518	the current studies of glycoproteins and structure of their glycoforms	500:569	Mass spectrometry (MS) is one of the most efficient tools used in the current studies of glycoproteins and structure of their glycoforms.
32441515	6	83	from	linkages	995:1002	arg1	glycopeptides					1014:1026	intact glycopeptides	1007:1026	intact glycopeptides	1007:1026	Using CE modulation, we were able to break selectively specific glycan linkages on intact glycopeptides and get, to some degree, structure-specific mass spectrometric signals.
32441515	2	84	theme	interaction-specificity	367:389	arg1	determinant					340:350	an important determinant	327:350	an important determinant of the protein interaction-specificity	327:389	The glycans attached to proteins represent an important determinant of the protein interaction-specificity and maintain the 3D structure of proteins.
32441515	1	85	theme	immune	266:271	arg1	responses					273:281	immune responses	266:281	immune responses	266:281	Glycosylation is a major post-translational modification of proteins that regulates many biological processes including protein folding, structure stability, receptor activation, and immune responses.
32441515	8	86	theme	additional	1344:1353	arg1	information					1366:1376	additional structural information	1344:1376	additional structural information including features specific to the chitobiose core	1344:1427	The complementary Y-ions, generated under optimized low CE (soft) conditions, provide additional structural information including features specific to the chitobiose core.
32441515	0	87	theme	Collision	4:12	arg1	Energy					14:19	Low Collision Energy	0:19	Low Collision Energy	0:19	Low Collision Energy Fragmentation in Structure-Specific Glycoproteomics Analysis.
34578800	4	0	theme	fine	674:677	arg1	differences					679:689	fine differences	674:689	fine differences in carbohydrate linkage structure	674:723	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	4	1	from	variation	798:806	arg1	composition					828:838	glycosyl residue composition	811:838	glycosyl residue composition	811:838	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	4	2	from	differences	679:689	arg1	structure					715:723	carbohydrate linkage structure	694:723	carbohydrate linkage structure	694:723	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	5	3	theme	different	979:987	arg1	arrangements					1000:1011	different structural arrangements	979:1011	different structural arrangements	979:1011	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	9	4	theme	linkage	1686:1692	arg1	structure					1694:1702	linkage structure	1686:1702	linkage structure	1686:1702	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	3	5	theme	derived	511:517	arg1	fibers					519:524	naturally derived fibers	501:524	naturally derived fibers	501:524	However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables.
34578800	0	6	theme	Human	95:99	arg1	Microbiota					105:114	Human Gut Microbiota	95:114	Human Gut Microbiota	95:114	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	8	7	theme	certain	1545:1551	arg1	taxa					1553:1556	certain taxa	1545:1556	certain taxa	1545:1556	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	7	8	from	glucans	1273:1279	arg1	outputs					1250:1256	community metabolic outputs	1230:1256	community metabolic outputs from identical glucans	1230:1279	We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures.
34578800	3	9	theme	sugar	539:543	arg1	composition					545:555	sugar composition	539:555	sugar composition	539:555	However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables.
34578800	4	10	theme	community	748:756	arg1	structure					758:766	microbial community structure	738:766	microbial community structure	738:766	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	6	11	dep	outputs	1096:1102	arg1	outputs					1096:1102	metabolic outputs	1086:1102	metabolic outputs (pH, gas, and short-chain fatty acid production)	1086:1151	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	6	11	dep	outputs	1096:1102	arg1	production					1141:1150	short-chain fatty acid production	1118:1150	short-chain fatty acid production	1118:1150	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	6	11	dep	outputs	1096:1102	arg1	gas					1109:1111	gas	1109:1111	gas	1109:1111	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	6	11	dep	outputs	1096:1102	arg1	pH					1105:1106	pH	1105:1106	pH	1105:1106	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	8	12	theme	specific	1369:1376	arg1	OTUs					1407:1410	OTUs	1407:1410	OTUs	1407:1410	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	8	12	theme	specific	1369:1376	arg1	units					1400:1404	specific operational taxonomic units	1369:1404	specific operational taxonomic units (OTUs)	1369:1411	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	2	13	from	labor	337:341	arg1	consumption					346:356	consumption	346:356	consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation	346:486	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	6	14	theme	rRNA	1185:1188	arg1	sequencing					1199:1208	rRNA amplicon sequencing	1185:1208	rRNA amplicon sequencing	1185:1208	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	5	15	from	each	1047:1050	arg1	inocula					1034:1040	fecal inocula	1028:1040	fecal inocula from each of three individuals	1028:1071	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	6	16	theme	short-chain	1118:1128	arg1	acid					1136:1139	short-chain fatty acid	1118:1139	short-chain fatty acid production	1118:1150	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	0	17	theme	Microbiota	105:114	arg1	Function					83:90	Function	83:90	Function	83:90	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	0	17	theme	Microbiota	105:114	arg1	Structure					69:77	Structure	69:77	Structure	69:77	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	9	18	theme	independent	1705:1715	arg1	structure					1694:1702	linkage structure	1686:1702	linkage structure	1686:1702	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	7	19	theme	microbiome	1337:1346	arg1	structures					1348:1357	divergent initial microbiome structures	1319:1357	divergent initial microbiome structures	1319:1357	We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures.
34578800	2	20	theme	possible	270:277	arg1	explanation					279:289	One possible explanation	266:289	One possible explanation	266:289	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	5	21	theme	available	892:900	arg1	glucans					920:926	commercially available soluble resistant glucans	879:926	commercially available soluble resistant glucans	879:926	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	0	22	theme	Gut	101:103	arg1	Microbiota					105:114	Human Gut Microbiota	95:114	Human Gut Microbiota	95:114	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	9	23	from	variation	1673:1681	arg1	structure					1694:1702	linkage structure	1686:1702	linkage structure	1686:1702	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	8	24	theme	taxonomic	1390:1398	arg1	OTUs					1407:1410	OTUs	1407:1410	OTUs	1407:1410	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	8	24	theme	taxonomic	1390:1398	arg1	units					1400:1404	specific operational taxonomic units	1369:1404	specific operational taxonomic units (OTUs)	1369:1411	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	0	25	theme	Carbohydrate	5:16	arg1	Structure					18:26	Fine Carbohydrate Structure	0:26	Fine Carbohydrate Structure of Dietary Resistant Glucans	0:55	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	7	26	theme	community	1230:1238	arg1	outputs					1250:1256	community metabolic outputs	1230:1256	community metabolic outputs from identical glucans	1230:1279	We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures.
34578800	9	27	theme	sugar	1720:1724	arg1	composition					1726:1736	sugar composition	1720:1736	sugar composition	1720:1736	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	4	28	theme	microbial	738:746	arg1	structure					758:766	microbial community structure	738:766	microbial community structure	738:766	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	1	29	theme	human	180:184	arg1	diversity					200:208	human gut microbial diversity	180:208	human gut microbial diversity	180:208	Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear.
34578800	0	30	theme	Fine	0:3	arg1	Structure					18:26	Fine Carbohydrate Structure	0:26	Fine Carbohydrate Structure of Dietary Resistant Glucans	0:55	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	9	31	theme	composition	1726:1736	arg1	independent					1705:1715	independent	1705:1715	independent	1705:1715	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	6	32	theme	community	1157:1165	arg1	structure					1167:1175	community structure	1157:1175	community structure	1157:1175	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	2	33	theme	carbohydrates	369:381	arg1	consumption					346:356	consumption	346:356	consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation	346:486	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	5	34	theme	fecal	1028:1032	arg1	inocula					1034:1040	fecal inocula	1028:1040	fecal inocula from each of three individuals	1028:1071	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	0	35	dep	Structure	69:77	arg1	the					65:67	the	65:67	the	65:67	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	2	36	theme	glycosidic	414:423	arg1	linkages					425:432	diverse glycosidic linkages	406:432	diverse glycosidic linkages that require specific cognate enzymes for degradation	406:486	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	3	37	link	derived	511:517	arg1	fibers					519:524	naturally derived fibers	501:524	naturally derived fibers	501:524	However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables.
34578800	6	38	theme	amplicon	1190:1197	arg1	sequencing					1199:1208	rRNA amplicon sequencing	1185:1208	rRNA amplicon sequencing	1185:1208	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	3	39	theme	linkage	561:567	arg1	structure					569:577	linkage structure	561:577	linkage structure	561:577	However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables.
34578800	2	40	theme	diverse	406:412	arg1	linkages					425:432	diverse glycosidic linkages	406:432	diverse glycosidic linkages that require specific cognate enzymes for degradation	406:486	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	0	41	theme	Resistant	39:47	arg1	Glucans					49:55	Dietary Resistant Glucans	31:55	Dietary Resistant Glucans	31:55	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	2	42	theme	metabolic	327:335	arg1	labor					337:341	metabolic labor	327:341	metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation	327:486	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	9	43	theme	compositional	1747:1759	arg1	responses					1776:1784	compositional and functional responses	1747:1784	compositional and functional responses of microbiota	1747:1798	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	6	44	theme	acid	1136:1139	arg1	outputs					1096:1102	metabolic outputs	1086:1102	metabolic outputs (pH, gas, and short-chain fatty acid production)	1086:1151	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	6	44	theme	acid	1136:1139	arg1	production					1141:1150	short-chain fatty acid production	1118:1150	short-chain fatty acid production	1118:1150	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	1	45	theme	gut	186:188	arg1	diversity					200:208	human gut microbial diversity	180:208	human gut microbial diversity	180:208	Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear.
34578800	9	46	theme	functional	1765:1774	arg1	responses					1776:1784	compositional and functional responses	1747:1784	compositional and functional responses of microbiota	1747:1798	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	0	47	theme	Dietary	31:37	arg1	Glucans					49:55	Dietary Resistant Glucans	31:55	Dietary Resistant Glucans	31:55	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	5	48	attach	linked	969:974	arg2	glucose					961:967	glucose	961:967	glucose linked in different structural arrangements	961:1011	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	5	48	attach	linked	969:974	arg3	arrangements					1000:1011	different structural arrangements	979:1011	different structural arrangements	979:1011	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	8	49	theme	context-dependent	1495:1511	arg1	ways					1513:1516	context-dependent ways	1495:1516	context-dependent ways	1495:1516	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	7	50	theme	divergent	1319:1327	arg1	structures					1348:1357	divergent initial microbiome structures	1319:1357	divergent initial microbiome structures	1319:1357	We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures.
34578800	5	51	theme	resistant	910:918	arg1	glucans					920:926	commercially available soluble resistant glucans	879:926	commercially available soluble resistant glucans	879:926	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	8	52	theme	operational	1378:1388	arg1	OTUs					1407:1410	OTUs	1407:1410	OTUs	1407:1410	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	8	52	theme	operational	1378:1388	arg1	units					1400:1404	specific operational taxonomic units	1369:1404	specific operational taxonomic units (OTUs)	1369:1411	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	3	53	theme	each	628:631	arg1	impact					618:623	the impact	614:623	the impact of each of these variables	614:650	However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables.
34578800	7	54	theme	identical	1263:1271	arg1	glucans					1273:1279	identical glucans	1263:1279	identical glucans	1263:1279	We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures.
34578800	4	55	theme	linkage	707:713	arg1	structure					715:723	carbohydrate linkage structure	694:723	carbohydrate linkage structure	694:723	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	0	56	theme	Glucans	49:55	arg1	Structure					18:26	Fine Carbohydrate Structure	0:26	Fine Carbohydrate Structure of Dietary Resistant Glucans	0:55	Fine Carbohydrate Structure of Dietary Resistant Glucans Governs the Structure and Function of Human Gut Microbiota.
34578800	6	57	theme	metabolic	1086:1094	arg1	outputs					1096:1102	metabolic outputs	1086:1102	metabolic outputs (pH, gas, and short-chain fatty acid production)	1086:1151	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	6	57	theme	metabolic	1086:1094	arg1	production					1141:1150	short-chain fatty acid production	1118:1150	short-chain fatty acid production	1118:1150	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	6	57	theme	metabolic	1086:1094	arg1	gas					1109:1111	gas	1109:1111	gas	1109:1111	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	6	57	theme	metabolic	1086:1094	arg1	pH					1105:1106	pH	1105:1106	pH	1105:1106	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	2	58	theme	cognate	456:462	arg1	enzymes					464:470	specific cognate enzymes	447:470	specific cognate enzymes	447:470	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	8	59	theme	growth	1436:1441	arg1	responses					1443:1451	growth responses	1436:1451	growth responses across individuals' microbiota	1436:1482	However, specific operational taxonomic units (OTUs) responded similarly in growth responses across individuals' microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others.
34578800	1	60	theme	Increased	117:125	arg1	consumption					141:151	Increased dietary fiber consumption	117:151	Increased dietary fiber consumption	117:151	Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear.
34578800	1	61	theme	dietary	127:133	arg1	consumption					141:151	Increased dietary fiber consumption	117:151	Increased dietary fiber consumption	117:151	Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear.
34578800	5	62	theme	soluble	902:908	arg1	glucans					920:926	commercially available soluble resistant glucans	879:926	commercially available soluble resistant glucans	879:926	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	9	63	theme	microbiota	1789:1798	arg1	responses					1776:1784	compositional and functional responses	1747:1784	compositional and functional responses of microbiota	1747:1798	Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.
34578800	5	64	theme	structural	989:998	arg1	arrangements					1000:1011	different structural arrangements	979:1011	different structural arrangements	979:1011	To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements, in vitro with fecal inocula from each of three individuals.
34578800	1	65	theme	fiber	135:139	arg1	consumption					141:151	Increased dietary fiber consumption	117:151	Increased dietary fiber consumption	117:151	Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear.
34578800	6	66	theme	fatty	1130:1134	arg1	acid					1136:1139	short-chain fatty acid	1118:1139	short-chain fatty acid production	1118:1150	We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing.
34578800	7	67	theme	metabolic	1240:1248	arg1	outputs					1250:1256	community metabolic outputs	1230:1256	community metabolic outputs from identical glucans	1230:1279	We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures.
34578800	4	68	theme	residue	820:826	arg1	composition					828:838	glycosyl residue composition	811:838	glycosyl residue composition	811:838	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	1	69	theme	microbial	190:198	arg1	diversity					200:208	human gut microbial diversity	180:208	human gut microbial diversity	180:208	Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear.
34578800	2	70	theme	complex	361:367	arg1	carbohydrates					369:381	complex carbohydrates	361:381	complex carbohydrates	361:381	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	7	71	theme	initial	1329:1335	arg1	structures					1348:1357	divergent initial microbiome structures	1319:1357	divergent initial microbiome structures	1319:1357	We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures.
34578800	4	72	theme	glycosyl	811:818	arg1	composition					828:838	glycosyl residue composition	811:838	glycosyl residue composition	811:838	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
34578800	2	73	theme	specific	447:454	arg1	enzymes					464:470	specific cognate enzymes	447:470	specific cognate enzymes	447:470	One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation.
34578800	4	74	theme	carbohydrate	694:705	arg1	structure					715:723	carbohydrate linkage structure	694:723	carbohydrate linkage structure	694:723	We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition.
32569746	6	0	from	those	988:992	arg1	distinct					974:981	distinct	974:981	distinct	974:981	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	1	from	similar	1105:1111	arg1	composition					1122:1132	sugar composition	1116:1132	sugar composition	1116:1132	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	10	2	theme	tunnel	1641:1646	arg1	"					1647:1647	this "half tunnel"	1630:1647	this "half tunnel"	1630:1647	Conceivably, this "half tunnel" would be suitable for binding the dolichylphosphate-linked acceptor substrate.
32569746	1	3	theme	post-translational	196:213	arg1	modification					215:226	a critical post-translational modification	185:226	a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life	185:325	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	9	4	theme	six-transmembrane	1517:1533	arg1	tunnel					1559:1564	the six-transmembrane helix cellulose-binding tunnel	1513:1564	the six-transmembrane helix cellulose-binding tunnel	1513:1564	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	11	5	theme	gene	1779:1782	arg1	cluster					1784:1790	a large gene cluster	1771:1790	a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases	1771:1857	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	9	6	theme	cellulose	1592:1600	arg1	BcsA					1611:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	10	7	theme	dolichylphosphate-linked	1683:1706	arg1	substrate					1717:1725	the dolichylphosphate-linked acceptor substrate	1679:1725	the dolichylphosphate-linked acceptor substrate	1679:1725	Conceivably, this "half tunnel" would be suitable for binding the dolichylphosphate-linked acceptor substrate.
32569746	4	8	theme	Pyrobaculum	663:673	arg1	calidifontis					675:686	The crenarchaeote Pyrobaculum calidifontis	645:686	The crenarchaeote Pyrobaculum calidifontis	645:686	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	0	9	theme	Minimal	113:119	arg1	Fold					145:148	an Unexpected Minimal Cellulose-Synthase-like Fold	99:148	an Unexpected Minimal Cellulose-Synthase-like Fold	99:148	A Transmembrane Crenarchaeal Mannosyltransferase Is Involved in N-Glycan Biosynthesis and Displays an Unexpected Minimal Cellulose-Synthase-like Fold.
32569746	9	10	theme	membrane	1406:1413	arg1	PcManGT					1425:1431	PcManGT	1425:1431	PcManGT	1425:1431	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	9	10	theme	membrane	1406:1413	arg1	domain					1415:1420	The membrane domain	1402:1420	The membrane domain of PcManGT	1402:1431	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	2	11	theme	boundless	340:348	arg1	glycosyltransferases					369:388	glycosyltransferases	369:388	glycosyltransferases	369:388	A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans.
32569746	2	11	theme	boundless	340:348	arg1	number					350:355	A seemingly boundless number	328:355	A seemingly boundless number of enzymes	328:366	A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans.
32569746	9	12	theme	cellulose-binding	1541:1557	arg1	tunnel					1559:1564	the six-transmembrane helix cellulose-binding tunnel	1513:1564	the six-transmembrane helix cellulose-binding tunnel	1513:1564	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	0	13	theme	Unexpected	102:111	arg1	Fold					145:148	an Unexpected Minimal Cellulose-Synthase-like Fold	99:148	an Unexpected Minimal Cellulose-Synthase-like Fold	99:148	A Transmembrane Crenarchaeal Mannosyltransferase Is Involved in N-Glycan Biosynthesis and Displays an Unexpected Minimal Cellulose-Synthase-like Fold.
32569746	7	14	theme	crystal	1207:1213	arg1	structure					1215:1223	crystal structure	1207:1223	crystal structure	1207:1223	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	3	15	theme	acceptor	624:631	arg1	substrates					633:642	relevant acceptor substrates	615:642	relevant acceptor substrates	615:642	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	9	16	theme	synthase	1602:1609	arg1	BcsA					1611:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	1	17	theme	life	322:325	arg1	domains					311:317	all domains	307:317	all domains of life	307:325	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	1	17	theme	life	322:325	arg1	life					322:325	life	322:325	life	322:325	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	10	18	theme	acceptor	1708:1715	arg1	substrate					1717:1725	the dolichylphosphate-linked acceptor substrate	1679:1725	the dolichylphosphate-linked acceptor substrate	1679:1725	Conceivably, this "half tunnel" would be suitable for binding the dolichylphosphate-linked acceptor substrate.
32569746	11	19	from	cluster	1784:1790	arg1	gene					1740:1743	The PcManGT gene	1728:1743	The PcManGT gene (Pcal_0472)	1728:1755	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	11	19	from	cluster	1784:1790	arg1	located					1760:1766	located	1760:1766	located	1760:1766	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	5	20	theme	envelope	888:895	arg1	proteins					911:918	cell envelope surface-layer proteins	883:918	cell envelope surface-layer proteins	883:918	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	9	21	theme	tunnel	1559:1564	arg1	"					1508:1508	"half"	1503:1508	"half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA	1503:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	9	22	theme	spheroides	1581:1590	arg1	BcsA					1611:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	11	23	theme	crenarchaeal	1914:1925	arg1	cluster					1954:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	0	24	theme	Cellulose-Synthase-like	121:143	arg1	Fold					145:148	an Unexpected Minimal Cellulose-Synthase-like Fold	99:148	an Unexpected Minimal Cellulose-Synthase-like Fold	99:148	A Transmembrane Crenarchaeal Mannosyltransferase Is Involved in N-Glycan Biosynthesis and Displays an Unexpected Minimal Cellulose-Synthase-like Fold.
32569746	9	25	theme	PcManGT	1425:1431	arg1	PcManGT					1425:1431	PcManGT	1425:1431	PcManGT	1425:1431	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	9	25	theme	PcManGT	1425:1431	arg1	domain					1415:1420	The membrane domain	1402:1420	The membrane domain of PcManGT	1402:1431	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	7	26	theme	member	1238:1243	arg1	characterization					1186:1201	characterization	1186:1201	characterization	1186:1201	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	7	26	theme	member	1238:1243	arg1	structure					1215:1223	crystal structure	1207:1223	crystal structure	1207:1223	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	5	27	located	found	874:878	arg1	proteins					911:918	cell envelope surface-layer proteins	883:918	cell envelope surface-layer proteins	883:918	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	5	27	located	found	874:878	arg1	pili					945:948	pili	945:948	pili	945:948	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	5	27	located	found	874:878	arg2	N-glycans					853:861	N-glycans	853:861	N-glycans	853:861	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	5	27	located	found	874:878	arg1	flagellins					930:939	archaeal flagellins	921:939	archaeal flagellins	921:939	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	5	27	located	found	874:878	arg1	archaea					844:850	archaea	844:850	archaea	844:850	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	7	28	theme	glycosyltransferase	1272:1290	arg1	member					1238:1243	the first member	1228:1243	the first member of a crenarchaeal membrane glycosyltransferase, PcManGT	1228:1299	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	2	29	theme	glycans	448:454	arg1	biosynthesis					411:422	the biosynthesis	407:422	the biosynthesis of these protein-linked glycans	407:454	A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans.
32569746	0	30	theme	Transmembrane	2:14	arg1	Mannosyltransferase					29:47	A Transmembrane Crenarchaeal Mannosyltransferase	0:47	A Transmembrane Crenarchaeal Mannosyltransferase	0:47	A Transmembrane Crenarchaeal Mannosyltransferase Is Involved in N-Glycan Biosynthesis and Displays an Unexpected Minimal Cellulose-Synthase-like Fold.
32569746	6	31	theme	high-mannose	1045:1056	arg1	N-glycan					1058:1065	the high-mannose N-glycan	1041:1065	the high-mannose N-glycan	1041:1065	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	31	theme	high-mannose	1045:1056	arg1	exception					1028:1036	one noteworthy exception	1013:1036	one noteworthy exception	1013:1036	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	31	theme	high-mannose	1045:1056	arg1	similar					1105:1111	similar	1105:1111	similar	1105:1111	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	32	from	composition	1122:1132	arg1	similar					1105:1111	similar	1105:1111	similar	1105:1111	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	32	from	composition	1122:1132	arg1	exception					1028:1036	one noteworthy exception	1013:1036	one noteworthy exception	1013:1036	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	32	from	composition	1122:1132	arg1	N-glycan					1058:1065	the high-mannose N-glycan	1041:1065	the high-mannose N-glycan	1041:1065	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	7	33	theme	membrane	1263:1270	arg1	PcManGT					1293:1299	PcManGT	1293:1299	PcManGT	1293:1299	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	7	33	theme	membrane	1263:1270	arg1	glycosyltransferase					1272:1290	a crenarchaeal membrane glycosyltransferase	1248:1290	a crenarchaeal membrane glycosyltransferase	1248:1290	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	2	34	theme	protein-linked	433:446	arg1	glycans					448:454	these protein-linked glycans	427:454	these protein-linked glycans	427:454	A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans.
32569746	5	35	theme	surface-layer	897:909	arg1	proteins					911:918	cell envelope surface-layer proteins	883:918	cell envelope surface-layer proteins	883:918	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	11	36	theme	N-glycosylation	1927:1941	arg1	cluster					1954:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	2	37	theme	enzymes	360:366	arg1	glycosyltransferases					369:388	glycosyltransferases	369:388	glycosyltransferases	369:388	A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans.
32569746	2	37	theme	enzymes	360:366	arg1	number					350:355	A seemingly boundless number	328:355	A seemingly boundless number of enzymes	328:366	A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans.
32569746	8	38	theme	dolichylphosphate-	1337:1354	arg1	mannosyltransferase					1381:1399	a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase	1329:1399	a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase	1329:1399	We show that the enzyme is a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase.
32569746	8	38	theme	dolichylphosphate-	1337:1354	arg1	enzyme					1319:1324	the enzyme	1315:1324	the enzyme	1315:1324	We show that the enzyme is a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase.
32569746	1	39	theme	vast	244:247	arg1	number					249:254	a vast number	242:254	a vast number of biological functions	242:278	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	11	40	from	located	1760:1766	arg1	cluster					1784:1790	a large gene cluster	1771:1790	a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases	1771:1857	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	4	41	theme	eukaryotic	820:829	arg1	archaea					723:729	archaea	723:729	archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor	723:838	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	4	41	theme	eukaryotic	820:829	arg1	ancestor					831:838	an eukaryotic ancestor	817:838	an eukaryotic ancestor	817:838	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	10	42	theme	half	1636:1639	arg1	"					1647:1647	this "half tunnel"	1630:1647	this "half tunnel"	1630:1647	Conceivably, this "half tunnel" would be suitable for binding the dolichylphosphate-linked acceptor substrate.
32569746	3	43	theme	substrates	633:642	arg1	proteins					587:594	integral membrane proteins	569:594	integral membrane proteins	569:594	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	3	43	theme	substrates	633:642	arg1	paucity					604:610	the paucity	600:610	the paucity of relevant acceptor substrates	600:642	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	3	43	theme	substrates	633:642	arg1	majority					554:561	the majority	550:561	the majority	550:561	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	5	44	theme	archaeal	921:928	arg1	flagellins					930:939	archaeal flagellins	921:939	archaeal flagellins	921:939	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	0	45	theme	Crenarchaeal	16:27	arg1	Mannosyltransferase					29:47	A Transmembrane Crenarchaeal Mannosyltransferase	0:47	A Transmembrane Crenarchaeal Mannosyltransferase	0:47	A Transmembrane Crenarchaeal Mannosyltransferase Is Involved in N-Glycan Biosynthesis and Displays an Unexpected Minimal Cellulose-Synthase-like Fold.
32569746	4	46	theme	crenarchaeote	649:661	arg1	calidifontis					675:686	The crenarchaeote Pyrobaculum calidifontis	645:686	The crenarchaeote Pyrobaculum calidifontis	645:686	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	2	47	link	protein-linked	433:446	arg1	glycans					448:454	these protein-linked glycans	427:454	these protein-linked glycans	427:454	A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans.
32569746	4	48	theme	archaea	723:729	arg1	superphylum					708:718	the TACK superphylum	699:718	the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor	699:838	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	3	49	theme	membrane	578:585	arg1	proteins					587:594	integral membrane proteins	569:594	integral membrane proteins	569:594	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	3	49	theme	membrane	578:585	arg1	majority					554:561	the majority	550:561	the majority	550:561	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	3	50	theme	integral	569:576	arg1	proteins					587:594	integral membrane proteins	569:594	integral membrane proteins	569:594	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	3	50	theme	integral	569:576	arg1	majority					554:561	the majority	550:561	the majority	550:561	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	8	51	theme	manganese-dependent	1361:1379	arg1	mannosyltransferase					1381:1399	a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase	1329:1399	a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase	1329:1399	We show that the enzyme is a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase.
32569746	8	51	theme	manganese-dependent	1361:1379	arg1	enzyme					1319:1324	the enzyme	1315:1324	the enzyme	1315:1324	We show that the enzyme is a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase.
32569746	8	52	theme	GDP-	1331:1334	arg1	mannosyltransferase					1381:1399	a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase	1329:1399	a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase	1329:1399	We show that the enzyme is a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase.
32569746	8	52	theme	GDP-	1331:1334	arg1	enzyme					1319:1324	the enzyme	1315:1324	the enzyme	1315:1324	We show that the enzyme is a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase.
32569746	1	53	theme	biological	259:268	arg1	functions					270:278	biological functions	259:278	biological functions	259:278	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	6	54	theme	sugar	1116:1120	arg1	composition					1122:1132	sugar composition	1116:1132	sugar composition	1116:1132	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	11	55	theme	gene	1949:1952	arg1	cluster					1954:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	9	56	theme	helix	1535:1539	arg1	tunnel					1559:1564	the six-transmembrane helix cellulose-binding tunnel	1513:1564	the six-transmembrane helix cellulose-binding tunnel	1513:1564	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	6	57	theme	Archaeal	951:958	arg1	N-glycans					960:968	Archaeal N-glycans	951:968	Archaeal N-glycans	951:968	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	1	58	theme	functions	270:278	arg1	number					249:254	a vast number	242:254	a vast number of biological functions	242:278	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	0	59	theme	N-Glycan	64:71	arg1	Biosynthesis					73:84	N-Glycan Biosynthesis	64:84	N-Glycan Biosynthesis	64:84	A Transmembrane Crenarchaeal Mannosyltransferase Is Involved in N-Glycan Biosynthesis and Displays an Unexpected Minimal Cellulose-Synthase-like Fold.
32569746	9	60	theme	Rhodobacter	1569:1579	arg1	BcsA					1611:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	5	61	theme	cell	883:886	arg1	proteins					911:918	cell envelope surface-layer proteins	883:918	cell envelope surface-layer proteins	883:918	In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili.
32569746	9	62	theme	transmembrane	1448:1460	arg1	helices					1462:1468	three transmembrane helices	1442:1468	three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA	1442:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	10	63	link	dolichylphosphate-linked	1683:1706	arg1	substrate					1717:1725	the dolichylphosphate-linked acceptor substrate	1679:1725	the dolichylphosphate-linked acceptor substrate	1679:1725	Conceivably, this "half tunnel" would be suitable for binding the dolichylphosphate-linked acceptor substrate.
32569746	3	64	theme	glycan-biosynthetic	461:479	arg1	glycosyltransferases					481:500	Few glycan-biosynthetic glycosyltransferases	457:500	Few glycan-biosynthetic glycosyltransferases	457:500	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	11	65	theme	PNG	1944:1946	arg1	cluster					1954:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	a crenarchaeal N-glycosylation (PNG) gene cluster	1912:1960	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	4	66	dep	archaea	723:729	arg1	Korarchaeota					777:788	Korarchaeota	777:788	Korarchaeota	777:788	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	4	66	dep	archaea	723:729	arg1	Aigarchaeota					748:759	Aigarchaeota	748:759	Aigarchaeota	748:759	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	1	67	theme	Protein	151:157	arg1	glycosylation					159:171	Protein glycosylation	151:171	Protein glycosylation	151:171	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	6	68	theme	noteworthy	1017:1026	arg1	N-glycan					1058:1065	the high-mannose N-glycan	1041:1065	the high-mannose N-glycan	1041:1065	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	68	theme	noteworthy	1017:1026	arg1	exception					1028:1036	one noteworthy exception	1013:1036	one noteworthy exception	1013:1036	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	6	68	theme	noteworthy	1017:1026	arg1	similar					1105:1111	similar	1105:1111	similar	1105:1111	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	7	69	theme	first	1232:1236	arg1	member					1238:1243	the first member	1228:1243	the first member of a crenarchaeal membrane glycosyltransferase, PcManGT	1228:1299	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	11	70	theme	PcManGT	1732:1738	arg1	gene					1740:1743	The PcManGT gene	1728:1743	The PcManGT gene (Pcal_0472)	1728:1755	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	11	70	theme	PcManGT	1732:1738	arg1	Pcal_0472					1746:1754	Pcal_0472	1746:1754	Pcal_0472	1746:1754	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	11	70	theme	PcManGT	1732:1738	arg1	located					1760:1766	located	1760:1766	located	1760:1766	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	9	71	theme	half	1504:1507	arg1	"					1508:1508	"half"	1503:1508	"half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA	1503:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	4	72	theme	TACK	703:706	arg1	superphylum					708:718	the TACK superphylum	699:718	the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor	699:838	The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor.
32569746	9	73	from	"	1508:1508	arg1	BcsA					1611:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	Rhodobacter spheroides cellulose synthase BcsA	1569:1614	The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with "half" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA.
32569746	3	74	theme	relevant	615:622	arg1	substrates					633:642	relevant acceptor substrates	615:642	relevant acceptor substrates	615:642	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	1	75	theme	living	283:288	arg1	organisms					290:298	living organisms	283:298	living organisms	283:298	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
32569746	11	76	located	located	1760:1766	arg2	located					1760:1766	located	1760:1766	located	1760:1766	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	11	76	located	located	1760:1766	arg2	Pcal_0472					1746:1754	Pcal_0472	1746:1754	Pcal_0472	1746:1754	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	11	76	located	located	1760:1766	arg1	cluster					1784:1790	a large gene cluster	1771:1790	a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases	1771:1857	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	11	76	located	located	1760:1766	arg2	gene					1740:1743	The PcManGT gene	1728:1743	The PcManGT gene (Pcal_0472)	1728:1755	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	6	77	theme	eukaryotic	1141:1150	arg1	counterpart					1152:1162	the eukaryotic counterpart	1137:1162	the eukaryotic counterpart	1137:1162	Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart.
32569746	7	78	dep	characterization	1186:1201	arg1	the					1182:1184	the	1182:1184	the	1182:1184	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	3	79	theme	Few	457:459	arg1	glycosyltransferases					481:500	Few glycan-biosynthetic glycosyltransferases	457:500	Few glycan-biosynthetic glycosyltransferases	457:500	Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates.
32569746	11	80	theme	large	1773:1777	arg1	cluster					1784:1790	a large gene cluster	1771:1790	a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases	1771:1857	The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.
32569746	7	81	theme	crenarchaeal	1250:1261	arg1	PcManGT					1293:1299	PcManGT	1293:1299	PcManGT	1293:1299	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	7	81	theme	crenarchaeal	1250:1261	arg1	glycosyltransferase					1272:1290	a crenarchaeal membrane glycosyltransferase	1248:1290	a crenarchaeal membrane glycosyltransferase	1248:1290	Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT.
32569746	1	82	theme	critical	187:194	arg1	modification					215:226	a critical post-translational modification	185:226	a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life	185:325	Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life.
33654088	0	0	theme	cancer-associated	81:97	arg1	glycans					107:113	cancer-associated complex glycans	81:113	cancer-associated complex glycans	81:113	Glycan chip based on structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans.
33654088	4	1	theme	uniform	744:750	arg1	biosynthesis					752:763	uniform biosynthesis	744:763	uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface	744:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	4	2	theme	glycans	833:839	arg1	biosynthesis					752:763	uniform biosynthesis	744:763	uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface	744:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	5	3	theme	H-related	1044:1052	arg1	glycans					1054:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	4	theme	MCF-7	984:988	arg1	cells					1004:1008	MCF-7 breast cancer cells	984:1008	MCF-7 breast cancer cells	984:1008	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	5	theme	on-chip	1015:1021	arg1	glycans					1054:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	0	6	theme	glycans	107:113	arg1	biosynthesis					65:76	on-chip biosynthesis	57:76	on-chip biosynthesis of cancer-associated complex glycans	57:113	Glycan chip based on structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans.
33654088	4	7	theme	stepwise	849:856	arg1	analyses					871:878	stepwise quantitative analyses	849:878	stepwise quantitative analyses of isolated products from the surface	849:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	3	8	theme	i-motif	576:582	arg1	linker					588:593	a pH-responsive i-motif DNA linker	560:593	a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner	560:690	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	2	9	theme	biosynthesized	338:351	arg1	glycans					353:359	biosynthesized glycans	338:359	biosynthesized glycans	338:359	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	0	10	theme	complex	99:105	arg1	glycans					107:113	cancer-associated complex glycans	81:113	cancer-associated complex glycans	81:113	Glycan chip based on structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans.
33654088	4	11	theme	related	817:823	arg1	glycans					833:839	its related complex glycans	813:839	its related complex glycans	813:839	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	3	12	theme	DNA	584:586	arg1	linker					588:593	a pH-responsive i-motif DNA linker	560:593	a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner	560:690	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	2	13	contain	have	301:304	arg1	methods					293:299	current methods	285:299	current methods	285:299	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	2	13	contain	have	301:304	arg2	limitations					311:321	some limitations	306:321	some limitations	306:321	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	3	14	theme	glycan	520:525	arg1	chip					527:530	a glycan chip	518:530	a glycan chip	518:530	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	5	15	theme	breast	990:995	arg1	cells					1004:1008	MCF-7 breast cancer cells	984:1008	MCF-7 breast cancer cells	984:1008	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	1	16	theme	useful	183:188	arg1	sources					205:211	useful complex glycan sources	183:211	useful complex glycan sources	183:211	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	0	17	theme	Glycan	0:5	arg1	chip					7:10	Glycan chip	0:10	Glycan chip	0:10	Glycan chip based on structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans.
33654088	1	18	theme	complex	190:196	arg1	sources					205:211	useful complex glycan sources	183:211	useful complex glycan sources	183:211	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	4	19	from	surface	910:916	arg1	analyses					871:878	stepwise quantitative analyses	849:878	stepwise quantitative analyses of isolated products from the surface	849:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	4	19	from	surface	910:916	arg1	products					892:899	isolated products	883:899	isolated products from the surface	883:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	5	20	theme	structure-switchable	1097:1116	arg1	platform					1147:1154	the structure-switchable DNA linker-based glycan chip platform	1093:1154	the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications	1093:1227	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	4	21	theme	hexasaccharide	794:807	arg1	biosynthesis					752:763	uniform biosynthesis	744:763	uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface	744:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	1	22	theme	glycan	198:203	arg1	sources					205:211	useful complex glycan sources	183:211	useful complex glycan sources	183:211	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	2	23	theme	unreliable	484:493	arg1	results					495:501	unequal and unreliable results	472:501	unequal and unreliable results	472:501	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	4	24	theme	cancer-associated	768:784	arg1	H					792:792	cancer-associated Globo H	768:792	cancer-associated Globo H hexasaccharide	768:807	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	4	25	theme	On-chip	693:699	arg1	glycosylations					711:724	On-chip enzymatic glycosylations	693:724	On-chip enzymatic glycosylations	693:724	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	4	26	theme	H	792:792	arg1	hexasaccharide					794:807	cancer-associated Globo H hexasaccharide	768:807	cancer-associated Globo H hexasaccharide	768:807	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	3	27	from	immobilization	610:623	arg1	surfaces					658:665	chip surfaces	653:665	chip surfaces	653:665	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	2	28	theme	glycan	429:434	arg1	structures					436:445	undefined glycan structures	419:445	undefined glycan structures on a surface	419:458	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	3	29	theme	glycans	642:648	arg1	isolation					629:637	isolation	629:637	isolation	629:637	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	3	29	theme	glycans	642:648	arg1	immobilization					610:623	immobilization	610:623	immobilization	610:623	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	3	30	dep	immobilization	610:623	arg1	the					606:608	the	606:608	the	606:608	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	5	31	theme	Globo	1038:1042	arg1	glycans					1054:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	32	theme	linker-based	1122:1133	arg1	platform					1147:1154	the structure-switchable DNA linker-based glycan chip platform	1093:1154	the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications	1093:1227	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	33	theme	platform	1147:1154	arg1	feasibility					1078:1088	the feasibility	1074:1088	the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications	1074:1227	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	2	34	theme	unequal	472:478	arg1	results					495:501	unequal and unreliable results	472:501	unequal and unreliable results	472:501	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	5	35	theme	biosynthesized	1023:1036	arg1	glycans					1054:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	3	36	theme	pH-dependent	672:683	arg1	manner					685:690	a pH-dependent manner	670:690	a pH-dependent manner	670:690	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	1	37	theme	On-chip	116:122	arg1	strategy					160:167	an effective strategy	147:167	an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously	147:273	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	1	37	theme	On-chip	116:122	arg1	biosynthesis					131:142	On-chip glycan biosynthesis	116:142	On-chip glycan biosynthesis	116:142	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	3	38	from	isolation	629:637	arg1	surfaces					658:665	chip surfaces	653:665	chip surfaces	653:665	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	1	39	theme	effective	150:158	arg1	strategy					160:167	an effective strategy	147:167	an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously	147:273	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	1	39	theme	effective	150:158	arg1	biosynthesis					131:142	On-chip glycan biosynthesis	116:142	On-chip glycan biosynthesis	116:142	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	0	40	theme	DNA	42:44	arg1	linker					46:51	structure-switchable DNA linker	21:51	structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans	21:113	Glycan chip based on structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans.
33654088	5	41	theme	interaction	930:940	arg1	analyses					942:949	Successful interaction analyses	919:949	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans	919:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	4	42	theme	products	892:899	arg1	analyses					871:878	stepwise quantitative analyses	849:878	stepwise quantitative analyses of isolated products from the surface	849:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	4	43	theme	enzymatic	701:709	arg1	glycosylations					711:724	On-chip enzymatic glycosylations	693:724	On-chip enzymatic glycosylations	693:724	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	5	44	theme	Successful	919:928	arg1	analyses					942:949	Successful interaction analyses	919:949	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans	919:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	0	45	theme	structure-switchable	21:40	arg1	linker					46:51	structure-switchable DNA linker	21:51	structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans	21:113	Glycan chip based on structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans.
33654088	5	46	theme	glycan-involved	1200:1214	arg1	applications					1216:1227	glycan-involved applications	1200:1227	glycan-involved applications	1200:1227	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	4	47	theme	isolated	883:890	arg1	products					892:899	isolated products	883:899	isolated products from the surface	883:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	2	48	from	structures	436:445	arg1	surface					452:458	a surface	450:458	a surface	450:458	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	1	49	theme	glycan-involved	231:245	arg1	applications					247:258	glycan-involved applications	231:258	glycan-involved applications	231:258	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	5	50	theme	H	969:969	arg1	antibody					971:978	the anti-Globo H antibody	954:978	the anti-Globo H antibody	954:978	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	51	theme	chip	1142:1145	arg1	platform					1147:1154	the structure-switchable DNA linker-based glycan chip platform	1093:1154	the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications	1093:1227	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	1	52	theme	glycan	124:129	arg1	strategy					160:167	an effective strategy	147:167	an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously	147:273	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	1	52	theme	glycan	124:129	arg1	biosynthesis					131:142	On-chip glycan biosynthesis	116:142	On-chip glycan biosynthesis	116:142	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	1	53	dep	strategy	160:167	arg1	preparing					221:229	preparing	221:229	preparing glycan-involved applications simultaneously	221:273	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	1	53	dep	strategy	160:167	arg1	preparing					173:181	preparing	173:181	preparing useful complex glycan sources	173:211	On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously.
33654088	5	54	theme	on-chip	1160:1166	arg1	biosynthesis					1183:1194	on-chip complex glycan biosynthesis	1160:1194	on-chip complex glycan biosynthesis	1160:1194	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	55	theme	cancer	997:1002	arg1	cells					1004:1008	MCF-7 breast cancer cells	984:1008	MCF-7 breast cancer cells	984:1008	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	56	with	analyses	942:949	arg1	glycans					1054:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	on-chip biosynthesized Globo H-related glycans	1015:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	4	57	theme	quantitative	858:869	arg1	analyses					871:878	stepwise quantitative analyses	849:878	stepwise quantitative analyses of isolated products from the surface	849:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	3	58	theme	chip	653:656	arg1	surfaces					658:665	chip surfaces	653:665	chip surfaces	653:665	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	5	59	theme	glycan	1135:1140	arg1	platform					1147:1154	the structure-switchable DNA linker-based glycan chip platform	1093:1154	the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications	1093:1227	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	4	60	theme	Globo	786:790	arg1	H					792:792	cancer-associated Globo H	768:792	cancer-associated Globo H hexasaccharide	768:807	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	5	61	theme	anti-Globo	958:967	arg1	antibody					971:978	the anti-Globo H antibody	954:978	the anti-Globo H antibody	954:978	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	3	62	theme	pH-responsive	562:574	arg1	linker					588:593	a pH-responsive i-motif DNA linker	560:593	a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner	560:690	In this work, a glycan chip is developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner.
33654088	5	63	theme	complex	1168:1174	arg1	biosynthesis					1183:1194	on-chip complex glycan biosynthesis	1160:1194	on-chip complex glycan biosynthesis	1160:1194	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	4	64	theme	complex	825:831	arg1	glycans					833:839	its related complex glycans	813:839	its related complex glycans	813:839	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	2	65	theme	enzymatic	376:384	arg1	reactions					386:394	enzymatic reactions	376:394	enzymatic reactions	376:394	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	5	66	theme	cells	1004:1008	arg1	analyses					942:949	Successful interaction analyses	919:949	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans	919:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	67	theme	glycan	1176:1181	arg1	biosynthesis					1183:1194	on-chip complex glycan biosynthesis	1160:1194	on-chip complex glycan biosynthesis	1160:1194	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	2	68	theme	current	285:291	arg1	methods					293:299	current methods	285:299	current methods	285:299	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	4	69	from	analyses	871:878	arg1	surface					910:916	the surface	906:916	the surface	906:916	On-chip enzymatic glycosylations are optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface.
33654088	2	70	theme	undefined	419:427	arg1	structures					436:445	undefined glycan structures	419:445	undefined glycan structures on a surface	419:458	However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results.
33654088	0	71	theme	on-chip	57:63	arg1	biosynthesis					65:76	on-chip biosynthesis	57:76	on-chip biosynthesis of cancer-associated complex glycans	57:113	Glycan chip based on structure-switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans.
33654088	5	72	theme	DNA	1118:1120	arg1	platform					1147:1154	the structure-switchable DNA linker-based glycan chip platform	1093:1154	the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications	1093:1227	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
33654088	5	73	theme	antibody	971:978	arg1	analyses					942:949	Successful interaction analyses	919:949	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans	919:1060	Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrate the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.
32461612	5	0	theme	density	725:731	arg1	comparison					693:702	a comparison	691:702	a comparison	691:702	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	6	1	theme	viral	1018:1022	arg1	proteins					1031:1038	class I viral fusion proteins	1010:1038	class I viral fusion proteins	1010:1038	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	4	2	theme	HKU1	669:672	arg1	CoVs					674:677	SARS and HKU1 CoVs	660:677	SARS and HKU1 CoVs	660:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	1	3	theme	pandemic	237:244	arg1	potential					246:254	pandemic potential	237:254	pandemic potential	237:254	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	6	4	theme	fusion	1024:1029	arg1	proteins					1031:1038	class I viral fusion proteins	1010:1038	class I viral fusion proteins	1010:1038	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	5	5	theme	coronavirus	736:746	arg1	spikes					748:753	coronavirus spikes	736:753	coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin	736:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	6	gly	glycoprotein	819:830	arg1	glycoprotein					819:830	Lassa virus glycoprotein	807:830	Lassa virus glycoprotein complex	807:838	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	6	7	theme	individual	1059:1068	arg1	compositions					1077:1088	individual glycan compositions	1059:1088	not only individual glycan compositions but also the immunological pressure	1050:1124	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	2	8	theme	humoral	329:335	arg1	response					344:351	the neutralizing humoral immune response	312:351	the neutralizing humoral immune response	312:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	6	9	theme	glycan	1070:1075	arg1	compositions					1077:1088	individual glycan compositions	1059:1088	not only individual glycan compositions but also the immunological pressure	1050:1124	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	0	10	from	Vulnerabilities	0:14	arg1	glycan					31:36	coronavirus glycan	19:36	coronavirus glycan	19:36	Vulnerabilities in coronavirus glycan shields despite extensive glycosylation.
32461612	3	11	link	N-linked	457:464	arg1	sites					480:484	66-87 N-linked glycosylation sites	451:484	66-87 N-linked glycosylation sites per trimeric spike	451:503	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	5	12	theme	immunogenic	922:932	arg1	epitopes					934:941	immunogenic epitopes	922:941	immunogenic epitopes	922:941	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	4	13	from	S	569:569	arg1	area					533:536	a specific area	522:536	a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	522:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	1	14	theme	Severe	79:84	arg1	SARS					114:117	SARS	114:117	SARS	114:117	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	14	theme	Severe	79:84	arg1	syndrome					104:111	Severe acute respiratory syndrome	79:111	Severe acute respiratory syndrome (SARS)	79:118	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	2	15	theme	neutralizing	316:327	arg1	response					344:351	the neutralizing humoral immune response	312:351	the neutralizing humoral immune response	312:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	3	16	theme	trimeric	490:497	arg1	spike					499:503	trimeric spike	490:503	trimeric spike	490:503	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	2	17	gly	glycoprotein	368:379	arg1	glycoprotein					368:379	the spike (S) glycoprotein	354:379	the spike (S) glycoprotein	354:379	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	2	17	gly	glycoprotein	368:379	arg1	target					302:307	the principal target	288:307	the principal target of the neutralizing humoral immune response	288:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	3	18	theme	glycosylation	466:478	arg1	sites					480:484	66-87 N-linked glycosylation sites	451:484	66-87 N-linked glycosylation sites per trimeric spike	451:503	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	1	19	theme	acute	86:90	arg1	SARS					114:117	SARS	114:117	SARS	114:117	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	19	theme	acute	86:90	arg1	syndrome					104:111	Severe acute respiratory syndrome	79:111	Severe acute respiratory syndrome (SARS)	79:118	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	5	20	theme	glycoprotein	819:830	arg1	complex					832:838	Lassa virus glycoprotein complex	807:838	Lassa virus glycoprotein complex	807:838	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	3	21	theme	S	394:394	arg1	proteins					396:403	Coronavirus S proteins	382:403	Coronavirus S proteins	382:403	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	5	22	theme	viral	766:770	arg1	proteins					772:779	other viral proteins	760:779	other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin	760:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	22	theme	viral	766:770	arg1	envelope					797:804	HIV-1 envelope	791:804	HIV-1 envelope	791:804	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	22	theme	viral	766:770	arg1	hemagglutinin					855:867	influenza hemagglutinin	845:867	influenza hemagglutinin	845:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	22	theme	viral	766:770	arg1	complex					832:838	Lassa virus glycoprotein complex	807:838	Lassa virus glycoprotein complex	807:838	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	4	23	theme	MERS	564:567	arg1	S					569:569	MERS S	564:569	MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	564:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	1	24	theme	respiratory	92:102	arg1	SARS					114:117	SARS	114:117	SARS	114:117	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	24	theme	respiratory	92:102	arg1	syndrome					104:111	Severe acute respiratory syndrome	79:111	Severe acute respiratory syndrome (SARS)	79:118	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	4	25	from	density	553:559	arg1	S					569:569	MERS S	564:569	MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	564:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	4	26	theme	glycan	546:551	arg1	density					553:559	high glycan density	541:559	high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	541:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	1	27	theme	syndrome	104:111	arg1	CoVs					179:182	CoVs	179:182	CoVs	179:182	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	27	theme	syndrome	104:111	arg1	coronaviruses					164:176	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses	79:176	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs)	79:183	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	27	theme	syndrome	104:111	arg1	pathogens					198:206	zoonotic pathogens	189:206	zoonotic pathogens with high fatality rates and pandemic potential	189:254	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	6	28	theme	immunological	1103:1115	arg1	pressure					1117:1124	the immunological pressure	1099:1124	not only individual glycan compositions but also the immunological pressure	1050:1124	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	4	29	theme	high	541:544	arg1	density					553:559	high glycan density	541:559	high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	541:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	6	30	theme	protein	1137:1143	arg1	surface					1145:1151	the protein surface	1133:1151	the protein surface	1133:1151	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	2	31	theme	S	365:365	arg1	glycoprotein					368:379	the spike (S) glycoprotein	354:379	the spike (S) glycoprotein	354:379	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	2	31	theme	S	365:365	arg1	target					302:307	the principal target	288:307	the principal target of the neutralizing humoral immune response	288:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	1	32	with	pathogens	198:206	arg1	rates					227:231	high fatality rates	213:231	high fatality rates	213:231	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	32	with	pathogens	198:206	arg1	potential					246:254	pandemic potential	237:254	pandemic potential	237:254	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	5	33	theme	known	898:902	arg1	role					904:907	a known role	896:907	a known role	896:907	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	6	34	theme	I	1016:1016	arg1	proteins					1031:1038	class I viral fusion proteins	1010:1038	class I viral fusion proteins	1010:1038	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	3	35	theme	N-linked	457:464	arg1	sites					480:484	66-87 N-linked glycosylation sites	451:484	66-87 N-linked glycosylation sites per trimeric spike	451:503	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	0	36	theme	coronavirus	19:29	arg1	glycan					31:36	coronavirus glycan	19:36	coronavirus glycan	19:36	Vulnerabilities in coronavirus glycan shields despite extensive glycosylation.
32461612	4	37	theme	density	553:559	arg1	area					533:536	a specific area	522:536	a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	522:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	2	38	theme	principal	292:300	arg1	glycoprotein					368:379	the spike (S) glycoprotein	354:379	the spike (S) glycoprotein	354:379	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	2	38	theme	principal	292:300	arg1	target					302:307	the principal target	288:307	the principal target of the neutralizing humoral immune response	288:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	1	39	theme	zoonotic	189:196	arg1	coronaviruses					164:176	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses	79:176	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs)	79:183	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	39	theme	zoonotic	189:196	arg1	pathogens					198:206	zoonotic pathogens	189:206	zoonotic pathogens with high fatality rates and pandemic potential	189:254	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	4	40	from	area	533:536	arg1	S					569:569	MERS S	564:569	MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	564:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	2	41	theme	immune	337:342	arg1	response					344:351	the neutralizing humoral immune response	312:351	the neutralizing humoral immune response	312:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	5	42	theme	Lassa	807:811	arg1	glycoprotein					819:830	Lassa virus glycoprotein	807:830	Lassa virus glycoprotein complex	807:838	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	3	43	gly	glycosylation	466:478	arg2	sites					480:484	66-87 N-linked glycosylation sites	451:484	66-87 N-linked glycosylation sites per trimeric spike	451:503	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	3	43	gly	glycosylation	466:478	arg2	66-87					451:455	66-87	451:455	66-87	451:455	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	4	44	theme	clusters	629:636	arg1	absent					650:655	absent	650:655	absent	650:655	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	4	44	theme	clusters	629:636	arg1	formation					591:599	the formation	587:599	the formation	587:599	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	4	45	theme	SARS	660:663	arg1	CoVs					674:677	SARS and HKU1 CoVs	660:677	SARS and HKU1 CoVs	660:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	5	46	theme	spikes	748:753	arg1	density					725:731	the global glycan density	707:731	the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin	707:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	4	47	theme	glycan	622:627	arg1	clusters					629:636	oligomannose-type glycan clusters	604:636	oligomannose-type glycan clusters	604:636	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	3	48	theme	Coronavirus	382:392	arg1	proteins					396:403	Coronavirus S proteins	382:403	Coronavirus S proteins	382:403	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	5	49	theme	influenza	845:853	arg1	hemagglutinin					855:867	influenza hemagglutinin	845:867	influenza hemagglutinin	845:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	50	theme	other	760:764	arg1	proteins					772:779	other viral proteins	760:779	other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin	760:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	50	theme	other	760:764	arg1	envelope					797:804	HIV-1 envelope	791:804	HIV-1 envelope	791:804	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	50	theme	other	760:764	arg1	hemagglutinin					855:867	influenza hemagglutinin	845:867	influenza hemagglutinin	845:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	50	theme	other	760:764	arg1	complex					832:838	Lassa virus glycoprotein complex	807:838	Lassa virus glycoprotein complex	807:838	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	2	51	theme	response	344:351	arg1	glycoprotein					368:379	the spike (S) glycoprotein	354:379	the spike (S) glycoprotein	354:379	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	2	51	theme	response	344:351	arg1	target					302:307	the principal target	288:307	the principal target of the neutralizing humoral immune response	288:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	0	52	theme	extensive	54:62	arg1	glycosylation					64:76	extensive glycosylation	54:76	extensive glycosylation	54:76	Vulnerabilities in coronavirus glycan shields despite extensive glycosylation.
32461612	6	53	theme	class	1010:1014	arg1	proteins					1031:1038	class I viral fusion proteins	1010:1038	class I viral fusion proteins	1010:1038	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	1	54	theme	Middle	124:129	arg1	MERS					158:161	MERS	158:161	MERS	158:161	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	54	theme	Middle	124:129	arg1	syndrome					148:155	Middle East respiratory syndrome	124:155	Middle East respiratory syndrome (MERS)	124:162	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	4	55	theme	specific	524:531	arg1	area					533:536	a specific area	522:536	a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs	522:677	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	2	56	theme	Vaccine	257:263	arg1	development					265:275	Vaccine development	257:275	Vaccine development	257:275	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	6	57	theme	glycosylation	989:1001	arg1	organisation					973:984	organisation	973:984	organisation of glycosylation across class I viral fusion proteins	973:1038	Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
32461612	1	58	theme	East	131:134	arg1	MERS					158:161	MERS	158:161	MERS	158:161	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	58	theme	East	131:134	arg1	syndrome					148:155	Middle East respiratory syndrome	124:155	Middle East respiratory syndrome (MERS)	124:162	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	59	theme	high	213:216	arg1	rates					227:231	high fatality rates	213:231	high fatality rates	213:231	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	5	60	with	spikes	748:753	arg1	proteins					772:779	other viral proteins	760:779	other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin	760:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	60	with	spikes	748:753	arg1	envelope					797:804	HIV-1 envelope	791:804	HIV-1 envelope	791:804	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	60	with	spikes	748:753	arg1	hemagglutinin					855:867	influenza hemagglutinin	845:867	influenza hemagglutinin	845:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	60	with	spikes	748:753	arg1	complex					832:838	Lassa virus glycoprotein complex	807:838	Lassa virus glycoprotein complex	807:838	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	1	61	theme	respiratory	136:146	arg1	MERS					158:161	MERS	158:161	MERS	158:161	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	61	theme	respiratory	136:146	arg1	syndrome					148:155	Middle East respiratory syndrome	124:155	Middle East respiratory syndrome (MERS)	124:162	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	62	theme	fatality	218:225	arg1	rates					227:231	high fatality rates	213:231	high fatality rates	213:231	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	5	63	theme	global	711:716	arg1	density					725:731	the global glycan density	707:731	the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin	707:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	64	theme	virus	813:817	arg1	glycoprotein					819:830	Lassa virus glycoprotein	807:830	Lassa virus glycoprotein complex	807:838	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	3	65	gly	glycosylated	421:432	arg1	proteins					396:403	Coronavirus S proteins	382:403	Coronavirus S proteins	382:403	Coronavirus S proteins are extensively glycosylated, encoding around 66-87 N-linked glycosylation sites per trimeric spike.
32461612	4	66	theme	oligomannose-type	604:620	arg1	clusters					629:636	oligomannose-type glycan clusters	604:636	oligomannose-type glycan clusters	604:636	Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs.
32461612	1	67	theme	syndrome	148:155	arg1	CoVs					179:182	CoVs	179:182	CoVs	179:182	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	67	theme	syndrome	148:155	arg1	coronaviruses					164:176	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses	79:176	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs)	79:183	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	1	67	theme	syndrome	148:155	arg1	pathogens					198:206	zoonotic pathogens	189:206	zoonotic pathogens with high fatality rates and pandemic potential	189:254	Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential.
32461612	5	68	theme	glycan	718:723	arg1	density					725:731	the global glycan density	707:731	the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin	707:867	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	5	69	theme	HIV-1	791:795	arg1	envelope					797:804	HIV-1 envelope	791:804	HIV-1 envelope	791:804	We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes.
32461612	2	70	theme	spike	358:362	arg1	glycoprotein					368:379	the spike (S) glycoprotein	354:379	the spike (S) glycoprotein	354:379	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32461612	2	70	theme	spike	358:362	arg1	target					302:307	the principal target	288:307	the principal target of the neutralizing humoral immune response	288:351	Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein.
32432921	3	0	theme	protein	300:306	arg1	hSP-D					311:315	hSP-D	311:315	hSP-D	311:315	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	3	0	theme	protein	300:306	arg1	D					308:308	Human surfactant protein D	283:308	Human surfactant protein D (hSP-D)	283:316	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	8	1	theme	protein	1355:1361	arg1	mass					1363:1366	the protein mass	1351:1366	the protein mass	1351:1366	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	6	2	theme	human	826:830	arg1	protein					832:838	human protein	826:838	human protein obtained from a natural source	826:869	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	7	3	from	PAP	1113:1115	arg1	activity					1083:1090	the activity	1079:1090	the activity of hSP-D from AF and PAP	1079:1115	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	8	4	theme	oligomeric	1240:1249	arg1	form					1251:1254	the most abundant oligomeric form	1222:1254	the most abundant oligomeric form	1222:1254	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	8	4	theme	oligomeric	1240:1249	arg1	balls					1206:1210	fuzzy balls	1200:1210	fuzzy balls (40%)	1200:1216	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	0	5	theme	natural	68:74	arg1	sources					76:82	different natural sources	58:82	different natural sources	58:82	Structure and activity of human surfactant protein D from different natural sources.
32432921	6	6	theme	natural	856:862	arg1	source					864:869	a natural source	854:869	a natural source	854:869	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	6	7	theme	quantitative	757:768	arg1	distribution					770:781	the quantitative distribution	753:781	the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source	753:869	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	7	8	theme	protein	1057:1063	arg1	site					1045:1048	the N-glycosylation site	1025:1048	the N-glycosylation site of the protein	1025:1063	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	7	8	theme	protein	1057:1063	arg1	protein					1057:1063	the protein	1053:1063	the protein	1053:1063	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	6	9	theme	forms	817:821	arg1	distribution					770:781	the quantitative distribution	753:781	the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source	753:869	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	2	10	theme	calcium-dependent	257:273	arg1	manner					275:280	a calcium-dependent manner	255:280	a calcium-dependent manner	255:280	It binds pathogens through its carbohydrate recognition domain in a calcium-dependent manner.
32432921	5	11	theme	nonpathological	666:680	arg1	protein					688:694	nonpathological human protein	666:694	nonpathological human protein in terms of structure and biological activity	666:740	However, PAP-hSP-D has never been directly compared with nonpathological human protein in terms of structure and biological activity.
32432921	8	12	theme	abundant	1231:1238	arg1	form					1251:1254	the most abundant oligomeric form	1222:1254	the most abundant oligomeric form	1222:1254	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	8	12	theme	abundant	1231:1238	arg1	balls					1206:1210	fuzzy balls	1200:1210	fuzzy balls (40%)	1200:1216	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	5	13	theme	human	682:686	arg1	protein					688:694	nonpathological human protein	666:694	nonpathological human protein in terms of structure and biological activity	666:740	However, PAP-hSP-D has never been directly compared with nonpathological human protein in terms of structure and biological activity.
32432921	7	14	from	AF	1106:1107	arg1	activity					1083:1090	the activity	1079:1090	the activity of hSP-D from AF and PAP	1079:1115	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	6	15	from	distribution	770:781	arg1	protein					832:838	human protein	826:838	human protein obtained from a natural source	826:869	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	9	16	attach	attached	1380:1387	arg2	glycan					1373:1378	The glycan	1369:1378	The glycan attached to the N-glycosylation site	1369:1415	The glycan attached to the N-glycosylation site was found to be composed of fucose, galactose, sialic acid, and N-acetylglucosamine.
32432921	9	16	attach	attached	1380:1387	arg1	site					1412:1415	the N-glycosylation site	1392:1415	the N-glycosylation site	1392:1415	The glycan attached to the N-glycosylation site was found to be composed of fucose, galactose, sialic acid, and N-acetylglucosamine.
32432921	7	17	gly	N-glycosylation	1029:1043	arg1	protein					1057:1063	the protein	1053:1063	the protein	1053:1063	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	7	17	gly	N-glycosylation	1029:1043	arg2	site					1045:1048	the N-glycosylation site	1025:1048	the N-glycosylation site of the protein	1025:1063	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	7	17	gly	N-glycosylation	1029:1043	arg2	protein					1057:1063	the protein	1053:1063	the protein	1053:1063	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	4	18	theme	oligomeric	591:600	arg1	forms					602:606	higher order oligomeric forms	578:606	higher order oligomeric forms	578:606	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	0	19	theme	protein	43:49	arg1	D					51:51	human surfactant protein D	26:51	human surfactant protein D	26:51	Structure and activity of human surfactant protein D from different natural sources.
32432921	8	20	with	form	1251:1254	arg1	both					1317:1320	both	1317:1320	both	1317:1320	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	4	21	theme	order	585:589	arg1	forms					602:606	higher order oligomeric forms	578:606	higher order oligomeric forms	578:606	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	3	22	theme	bronchoalveolar	351:365	arg1	lavage					367:372	bronchoalveolar lavage	351:372	bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF)	351:465	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	5	23	theme	structure	708:716	arg1	terms					699:703	terms	699:703	terms of structure and biological activity	699:740	However, PAP-hSP-D has never been directly compared with nonpathological human protein in terms of structure and biological activity.
32432921	7	24	theme	N-glycosylation	1029:1043	arg1	site					1045:1048	the N-glycosylation site	1025:1048	the N-glycosylation site of the protein	1025:1063	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	7	24	theme	N-glycosylation	1029:1043	arg1	protein					1057:1063	the protein	1053:1063	the protein	1053:1063	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	10	25	from	AF	1689:1690	arg1	hSP-D					1678:1682	hSP-D	1678:1682	hSP-D from AF	1678:1690	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	5	26	dep	protein	688:694	arg1	been					638:641	been	638:641	has never been directly compared with nonpathological human protein in terms of structure and biological activity	628:740	However, PAP-hSP-D has never been directly compared with nonpathological human protein in terms of structure and biological activity.
32432921	3	27	theme	pulmonary	401:409	arg1	proteinosis					420:430	pulmonary alveolar proteinosis	401:430	pulmonary alveolar proteinosis (PAP)	401:436	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	3	27	theme	pulmonary	401:409	arg1	PAP					433:435	PAP	433:435	PAP	433:435	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	7	28	theme	hSP-D	1095:1099	arg1	activity					1083:1090	the activity	1079:1090	the activity of hSP-D from AF and PAP	1079:1115	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	1	29	theme	Surfactant	85:94	arg1	lectin					125:130	a C-type lectin	116:130	a C-type lectin that participates in the innate immune defense of lungs	116:186	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	1	29	theme	Surfactant	85:94	arg1	SP-D					107:110	SP-D	107:110	SP-D	107:110	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	1	29	theme	Surfactant	85:94	arg1	D					104:104	Surfactant protein D	85:104	Surfactant protein D (SP-D)	85:111	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	3	30	theme	alveolar	411:418	arg1	proteinosis					420:430	pulmonary alveolar proteinosis	401:430	pulmonary alveolar proteinosis (PAP)	401:436	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	3	30	theme	alveolar	411:418	arg1	PAP					433:435	PAP	433:435	PAP	433:435	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	9	31	gly	N-glycosylation	1396:1410	arg2	site					1412:1415	the N-glycosylation site	1392:1415	the N-glycosylation site	1392:1415	The glycan attached to the N-glycosylation site was found to be composed of fucose, galactose, sialic acid, and N-acetylglucosamine.
32432921	1	32	theme	protein	96:102	arg1	lectin					125:130	a C-type lectin	116:130	a C-type lectin that participates in the innate immune defense of lungs	116:186	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	1	32	theme	protein	96:102	arg1	SP-D					107:110	SP-D	107:110	SP-D	107:110	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	1	32	theme	protein	96:102	arg1	D					104:104	Surfactant protein D	85:104	Surfactant protein D (SP-D)	85:111	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	1	33	theme	immune	164:169	arg1	defense					171:177	the innate immune defense	153:177	the innate immune defense of lungs	153:186	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	0	34	from	sources	76:82	arg1	activity					14:21	activity	14:21	activity	14:21	Structure and activity of human surfactant protein D from different natural sources.
32432921	0	34	from	sources	76:82	arg1	Structure					0:8	Structure	0:8	Structure	0:8	Structure and activity of human surfactant protein D from different natural sources.
32432921	10	35	theme	functional	1518:1527	arg1	assays					1529:1534	the functional assays	1514:1534	the functional assays performed	1514:1544	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	0	36	theme	surfactant	32:41	arg1	D					51:51	human surfactant protein D	26:51	human surfactant protein D	26:51	Structure and activity of human surfactant protein D from different natural sources.
32432921	5	37	from	protein	688:694	arg1	terms					699:703	terms	699:703	terms of structure and biological activity	699:740	However, PAP-hSP-D has never been directly compared with nonpathological human protein in terms of structure and biological activity.
32432921	10	38	theme	large	1648:1652	arg1	oligomers					1654:1662	large oligomers	1648:1662	large oligomers	1648:1662	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	1	39	theme	innate	157:162	arg1	defense					171:177	the innate immune defense	153:177	the innate immune defense of lungs	153:186	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	4	40	theme	higher	578:583	arg1	forms					602:606	higher order oligomeric forms	578:606	higher order oligomeric forms	578:606	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	0	41	theme	human	26:30	arg1	D					51:51	human surfactant protein D	26:51	human surfactant protein D	26:51	Structure and activity of human surfactant protein D from different natural sources.
32432921	5	42	theme	biological	722:731	arg1	activity					733:740	biological activity	722:740	biological activity	722:740	However, PAP-hSP-D has never been directly compared with nonpathological human protein in terms of structure and biological activity.
32432921	6	43	theme	oligomeric	806:815	arg1	forms					817:821	the different hSP-D oligomeric forms	786:821	the different hSP-D oligomeric forms	786:821	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	1	44	theme	lungs	182:186	arg1	defense					171:177	the innate immune defense	153:177	the innate immune defense of lungs	153:186	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	0	45	theme	D	51:51	arg1	activity					14:21	activity	14:21	activity	14:21	Structure and activity of human surfactant protein D from different natural sources.
32432921	0	45	theme	D	51:51	arg1	Structure					0:8	Structure	0:8	Structure	0:8	Structure and activity of human surfactant protein D from different natural sources.
32432921	3	46	theme	Human	283:287	arg1	hSP-D					311:315	hSP-D	311:315	hSP-D	311:315	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	3	46	theme	Human	283:287	arg1	D					308:308	Human surfactant protein D	283:308	Human surfactant protein D (hSP-D)	283:316	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	6	47	theme	hSP-D	800:804	arg1	forms					817:821	the different hSP-D oligomeric forms	786:821	the different hSP-D oligomeric forms	786:821	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	10	48	theme	proportion	1634:1643	arg1	consequence					1608:1618	a consequence	1606:1618	a consequence of its higher proportion of large oligomers	1606:1662	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	10	48	theme	proportion	1634:1643	arg1	potency					1585:1591	higher potency	1578:1591	higher potency	1578:1591	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	7	49	theme	AF-hSP-D	963:970	arg1	oligomers					972:980	AF-hSP-D oligomers	963:980	AF-hSP-D oligomers	963:980	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	3	50	theme	patients	377:384	arg1	lavage					367:372	bronchoalveolar lavage	351:372	bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF)	351:465	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	4	51	theme	disease	492:498	arg1	hSP-D					501:505	hSP-D	501:505	hSP-D obtained from PAP	501:523	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	4	51	theme	disease	492:498	arg1	consequence					473:483	a consequence	471:483	a consequence of the disease	471:498	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	3	52	theme	surfactant	289:298	arg1	hSP-D					311:315	hSP-D	311:315	hSP-D	311:315	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	3	52	theme	surfactant	289:298	arg1	D					308:308	Human surfactant protein D	283:308	Human surfactant protein D (hSP-D)	283:316	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	6	53	theme	different	790:798	arg1	forms					817:821	the different hSP-D oligomeric forms	786:821	the different hSP-D oligomeric forms	786:821	Moreover, the quantitative distribution of the different hSP-D oligomeric forms in human protein obtained from a natural source has never been evaluated.
32432921	10	54	theme	higher	1627:1632	arg1	proportion					1634:1643	its higher proportion	1623:1643	its higher proportion of large oligomers	1623:1662	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	7	55	theme	quantitative	934:945	arg1	distribution					947:958	the quantitative distribution	930:958	the quantitative distribution of AF-hSP-D oligomers	930:980	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	10	56	theme	oligomers	1654:1662	arg1	proportion					1634:1643	its higher proportion	1623:1643	its higher proportion of large oligomers	1623:1662	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	7	57	theme	oligomers	972:980	arg1	distribution					947:958	the quantitative distribution	930:958	the quantitative distribution of AF-hSP-D oligomers	930:980	In this work, we have determined the quantitative distribution of AF-hSP-D oligomers, characterized the sugars attached through the N-glycosylation site of the protein, and compared the activity of hSP-D from AF and PAP with respect to their ability to bind and agglutinate bacteria.
32432921	9	58	theme	sialic	1464:1469	arg1	acid					1471:1474	sialic acid	1464:1474	sialic acid	1464:1474	The glycan attached to the N-glycosylation site was found to be composed of fucose, galactose, sialic acid, and N-acetylglucosamine.
32432921	2	59	theme	recognition	233:243	arg1	domain					245:250	its carbohydrate recognition domain	216:250	its carbohydrate recognition domain	216:250	It binds pathogens through its carbohydrate recognition domain in a calcium-dependent manner.
32432921	3	60	theme	amniotic	447:454	arg1	AF					463:464	AF	463:464	AF	463:464	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	3	60	theme	amniotic	447:454	arg1	fluid					456:460	amniotic fluid	447:460	amniotic fluid (AF)	447:465	Human surfactant protein D (hSP-D) has been routinely obtained from bronchoalveolar lavage of patients suffering from pulmonary alveolar proteinosis (PAP) and from amniotic fluid (AF).
32432921	8	61	from	form	1251:1254	arg1	AF-hSP-D					1259:1266	AF-hSP-D	1259:1266	AF-hSP-D	1259:1266	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	9	62	theme	N-glycosylation	1396:1410	arg1	site					1412:1415	the N-glycosylation site	1392:1415	the N-glycosylation site	1392:1415	The glycan attached to the N-glycosylation site was found to be composed of fucose, galactose, sialic acid, and N-acetylglucosamine.
32432921	2	63	theme	carbohydrate	220:231	arg1	domain					245:250	its carbohydrate recognition domain	216:250	its carbohydrate recognition domain	216:250	It binds pathogens through its carbohydrate recognition domain in a calcium-dependent manner.
32432921	4	64	theme	higher	537:542	arg1	amounts					544:550	higher amounts	537:550	higher amounts	537:550	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	0	65	theme	different	58:66	arg1	sources					76:82	different natural sources	58:82	different natural sources	58:82	Structure and activity of human surfactant protein D from different natural sources.
32432921	4	66	located	found	528:532	arg1	amounts					544:550	higher amounts	537:550	higher amounts	537:550	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	4	66	located	found	528:532	arg2	hSP-D					501:505	hSP-D	501:505	hSP-D obtained from PAP	501:523	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	4	66	located	found	528:532	arg2	consequence					473:483	a consequence	471:483	a consequence of the disease	471:498	As a consequence of the disease, hSP-D obtained from PAP is found in higher amounts and is mainly composed of higher order oligomeric forms.
32432921	10	67	theme	higher	1578:1583	arg1	consequence					1608:1618	a consequence	1606:1618	a consequence of its higher proportion of large oligomers	1606:1662	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	10	67	theme	higher	1578:1583	arg1	potency					1585:1591	higher potency	1578:1591	higher potency	1578:1591	Finally, in the functional assays performed, hSP-D obtained from PAP showed higher potency, probably as a consequence of its higher proportion of large oligomers compared with hSP-D from AF.
32432921	5	68	theme	activity	733:740	arg1	terms					699:703	terms	699:703	terms of structure and biological activity	699:740	However, PAP-hSP-D has never been directly compared with nonpathological human protein in terms of structure and biological activity.
32432921	8	69	theme	mass	1363:1366	arg1	%					1346:1346	73%	1344:1346	73% of the protein mass	1344:1366	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	8	69	theme	mass	1363:1366	arg1	mass					1363:1366	the protein mass	1351:1366	the protein mass	1351:1366	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	8	70	theme	fuzzy	1200:1204	arg1	form					1251:1254	the most abundant oligomeric form	1222:1254	the most abundant oligomeric form	1222:1254	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	8	70	theme	fuzzy	1200:1204	arg1	balls					1206:1210	fuzzy balls	1200:1210	fuzzy balls (40%)	1200:1216	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	8	70	theme	fuzzy	1200:1204	arg1	%					1215:1215	40%	1213:1215	40%	1213:1215	We have found that fuzzy balls (40%) are the most abundant oligomeric form in AF-hSP-D, very closely followed by dodecamers (33%), with both together constituting 73% of the protein mass.
32432921	1	71	theme	C-type	118:123	arg1	lectin					125:130	a C-type lectin	116:130	a C-type lectin that participates in the innate immune defense of lungs	116:186	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
32432921	1	71	theme	C-type	118:123	arg1	D					104:104	Surfactant protein D	85:104	Surfactant protein D (SP-D)	85:111	Surfactant protein D (SP-D) is a C-type lectin that participates in the innate immune defense of lungs.
31973075	7	0	theme	structures	1095:1104	arg1	importance					1062:1071	the utmost importance	1051:1071	the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting	1051:1159	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	1	1	theme	tumor	172:176	arg1	phenotypes					178:187	increased aggressive tumor phenotypes	151:187	increased aggressive tumor phenotypes	151:187	CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes.
31973075	7	2	dep	detection	975:983	arg1	the					971:973	the	971:973	the	971:973	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	5	3	theme	CD44v9	694:699	arg1	detection					681:689	the detection	677:689	the detection of CD44v9 by monoclonal antibodies	677:724	In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies.
31973075	7	4	theme	cancer-related	1007:1020	arg1	isoform					1029:1035	this cancer-related CD44v9 isoform	1002:1035	this cancer-related CD44v9 isoform	1002:1035	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	0	5	from	Impact	0:5	arg1	Detection					66:74	Gastric-Cancer-Associated CD44v9 Detection	33:74	Gastric-Cancer-Associated CD44v9 Detection	33:74	Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection.
31973075	5	6	theme	glycoengineered	636:650	arg1	models					667:672	glycoengineered gastric cancer models	636:672	glycoengineered gastric cancer models	636:672	In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies.
31973075	7	7	theme	significant	911:921	arg1	implications					923:934	significant implications	911:934	significant implications in clinical applications	911:959	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	5	8	theme	monoclonal	704:713	arg1	antibodies					715:724	monoclonal antibodies	704:724	monoclonal antibodies	704:724	In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies.
31973075	5	9	theme	gastric	652:658	arg1	models					667:672	glycoengineered gastric cancer models	636:672	glycoengineered gastric cancer models	636:672	In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies.
31973075	1	10	theme	CD44	77:80	arg1	isoforms					90:97	CD44 variant isoforms	77:97	CD44 variant isoforms	77:97	CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes.
31973075	6	11	theme	technical	760:768	arg1	approaches					770:779	different technical approaches	750:779	different technical approaches	750:779	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	3	12	from	Immunodetection	303:317	arg1	tissue					357:362	tumor tissue	351:362	tumor tissue	351:362	Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies.
31973075	5	13	theme	cancer	660:665	arg1	models					667:672	glycoengineered gastric cancer models	636:672	glycoengineered gastric cancer models	636:672	In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies.
31973075	1	14	theme	variant	82:88	arg1	isoforms					90:97	CD44 variant isoforms	77:97	CD44 variant isoforms	77:97	CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes.
31973075	6	15	theme	different	750:758	arg1	approaches					770:779	different technical approaches	750:779	different technical approaches	750:779	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	4	16	theme	protein	525:531	arg1	glycosylation					533:545	CD44 protein glycosylation	520:545	CD44 protein glycosylation	520:545	However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded.
31973075	2	17	theme	cancer	289:294	arg1	cells					296:300	human gastrointestinal cancer cells	266:300	human gastrointestinal cancer cells	266:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	3	18	theme	specific	405:412	arg1	antibodies					425:434	specific monoclonal antibodies	405:434	specific monoclonal antibodies	405:434	Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies.
31973075	4	19	theme	CD44	520:523	arg1	glycosylation					533:545	CD44 protein glycosylation	520:545	CD44 protein glycosylation	520:545	However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded.
31973075	7	20	theme	therapy	1143:1149	arg1	targeting					1151:1159	therapy targeting	1143:1159	therapy targeting	1143:1159	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	3	21	theme	monoclonal	414:423	arg1	antibodies					425:434	specific monoclonal antibodies	405:434	specific monoclonal antibodies	405:434	Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies.
31973075	4	22	theme	structural	450:459	arg1	variability					461:471	the structural variability	446:471	the structural variability conferred by both the alternative splicing and CD44 protein glycosylation	446:545	However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded.
31973075	7	23	contain	have	906:909	arg1	findings					893:900	These findings	887:900	These findings	887:900	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	7	23	contain	have	906:909	arg2	implications					923:934	significant implications	911:934	significant implications in clinical applications	911:959	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	0	24	theme	O-glycans	20:28	arg1	Impact					0:5	Impact	0:5	Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection.	0:75	Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection.
31973075	5	25	theme	O-glycosylation	614:628	arg1	role					606:609	the role	602:609	the role of O-glycosylation	602:628	In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies.
31973075	7	26	theme	considering	1076:1086	arg1	structures					1095:1104	considering glycan structures	1076:1104	considering glycan structures	1076:1104	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	0	27	theme	Truncated	10:18	arg1	O-glycans					20:28	Truncated O-glycans	10:28	Truncated O-glycans	10:28	Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection.
31973075	7	28	from	implications	923:934	arg1	applications					948:959	clinical applications	939:959	clinical applications	939:959	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	7	29	from	importance	1062:1071	arg1	detection					1126:1134	cancer biomarker detection	1109:1134	cancer biomarker detection	1109:1134	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	7	29	from	importance	1062:1071	arg1	targeting					1151:1159	therapy targeting	1143:1159	therapy targeting	1143:1159	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	0	30	theme	Gastric-Cancer-Associated	33:57	arg1	Detection					66:74	Gastric-Cancer-Associated CD44v9 Detection	33:74	Gastric-Cancer-Associated CD44v9 Detection	33:74	Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection.
31973075	7	31	theme	biomarker	1116:1124	arg1	detection					1126:1134	cancer biomarker detection	1109:1134	cancer biomarker detection	1109:1134	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	2	32	theme	isoforms	244:251	arg1	CD44v9					194:199	The CD44v9	190:199	The CD44v9	190:199	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	2	32	theme	isoforms	244:251	arg1	isoforms					244:251	the major protein splice variant isoforms	211:251	the major protein splice variant isoforms expressed in human gastrointestinal cancer cells	211:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	2	32	theme	isoforms	244:251	arg1	one					204:206	one	204:206	one	204:206	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	4	33	theme	alternative	495:505	arg1	splicing					507:514	the alternative splicing	491:514	the alternative splicing	491:514	However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded.
31973075	2	34	theme	variant	236:242	arg1	isoforms					244:251	the major protein splice variant isoforms	211:251	the major protein splice variant isoforms expressed in human gastrointestinal cancer cells	211:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	6	35	theme	O-glycan	812:819	arg1	structures					821:830	immature O-glycan structures	803:830	immature O-glycan structures	803:830	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	6	35	theme	O-glycan	812:819	arg1	STn					848:850	STn	848:850	STn	848:850	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	6	35	theme	O-glycan	812:819	arg1	Tn					841:842	Tn	841:842	Tn	841:842	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	3	36	theme	isoforms	327:334	arg1	Immunodetection					303:317	Immunodetection	303:317	Immunodetection of CD44 isoforms like CD44v9 in tumor tissue	303:362	Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies.
31973075	2	37	theme	splice	229:234	arg1	isoforms					244:251	the major protein splice variant isoforms	211:251	the major protein splice variant isoforms expressed in human gastrointestinal cancer cells	211:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	6	38	theme	immature	803:810	arg1	structures					821:830	immature O-glycan structures	803:830	immature O-glycan structures	803:830	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	6	38	theme	immature	803:810	arg1	STn					848:850	STn	848:850	STn	848:850	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	6	38	theme	immature	803:810	arg1	Tn					841:842	Tn	841:842	Tn	841:842	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	0	39	theme	CD44v9	59:64	arg1	Detection					66:74	Gastric-Cancer-Associated CD44v9 Detection	33:74	Gastric-Cancer-Associated CD44v9 Detection	33:74	Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection.
31973075	7	40	theme	cancer	1109:1114	arg1	detection					1126:1134	cancer biomarker detection	1109:1134	cancer biomarker detection	1109:1134	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	2	41	theme	major	215:219	arg1	isoforms					244:251	the major protein splice variant isoforms	211:251	the major protein splice variant isoforms expressed in human gastrointestinal cancer cells	211:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	2	42	theme	protein	221:227	arg1	isoforms					244:251	the major protein splice variant isoforms	211:251	the major protein splice variant isoforms expressed in human gastrointestinal cancer cells	211:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	7	43	theme	utmost	1055:1060	arg1	importance					1062:1071	the utmost importance	1051:1071	the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting	1051:1159	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	6	44	theme	structures	821:830	arg1	presence					791:798	the presence	787:798	the presence of immature O-glycan structures, such as Tn and STn,	787:851	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	7	45	theme	glycan	1088:1093	arg1	structures					1095:1104	considering glycan structures	1076:1104	considering glycan structures	1076:1104	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	6	46	theme	protein	868:874	arg1	detection					876:884	CD44v9 protein detection	861:884	CD44v9 protein detection	861:884	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	2	47	theme	gastrointestinal	272:287	arg1	cells					296:300	human gastrointestinal cancer cells	266:300	human gastrointestinal cancer cells	266:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	7	48	theme	CD44v9	1022:1027	arg1	isoform					1029:1035	this cancer-related CD44v9 isoform	1002:1035	this cancer-related CD44v9 isoform	1002:1035	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	7	49	theme	isoform	1029:1035	arg1	targeting					989:997	targeting	989:997	targeting	989:997	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	7	49	theme	isoform	1029:1035	arg1	detection					975:983	detection	975:983	detection	975:983	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	3	50	theme	CD44	322:325	arg1	isoforms					327:334	CD44 isoforms	322:334	CD44 isoforms like CD44v9	322:346	Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies.
31973075	6	51	theme	CD44v9	861:866	arg1	detection					876:884	CD44v9 protein detection	861:884	CD44v9 protein detection	861:884	We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection.
31973075	2	52	theme	human	266:270	arg1	cells					296:300	human gastrointestinal cancer cells	266:300	human gastrointestinal cancer cells	266:300	The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells.
31973075	7	53	theme	clinical	939:946	arg1	applications					948:959	clinical applications	939:959	clinical applications	939:959	These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.
31973075	3	54	theme	tumor	351:355	arg1	tissue					357:362	tumor tissue	351:362	tumor tissue	351:362	Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies.
31973075	1	55	theme	increased	151:159	arg1	phenotypes					178:187	increased aggressive tumor phenotypes	151:187	increased aggressive tumor phenotypes	151:187	CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes.
31973075	5	56	theme	present	570:576	arg1	work					578:581	the present work	566:581	the present work	566:581	In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies.
31973075	1	57	theme	aggressive	161:170	arg1	phenotypes					178:187	increased aggressive tumor phenotypes	151:187	increased aggressive tumor phenotypes	151:187	CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes.
34450331	8	0	theme	acute	1587:1591	arg1	diseases					1605:1612	acute and chronic diseases	1587:1612	acute and chronic diseases	1587:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	6	1	theme	3D	1101:1102	arg1	analysis					1114:1121	the LDA and 3D structure analysis	1089:1121	analysis	1114:1121	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	11	2	theme	X-ray	1956:1960	arg1	techniques					2055:2064	the major techniques	2045:2064	the major techniques applied to elucidate macromolecule structures	2045:2110	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	2	theme	X-ray	1956:1960	arg1	techniques					2030:2039	cryoEM techniques	2023:2039	cryoEM techniques	2023:2039	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	2	theme	X-ray	1956:1960	arg1	spectroscopy					2006:2017	nuclear magnetic resonance spectroscopy	1979:2017	nuclear magnetic resonance spectroscopy	1979:2017	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	2	theme	X-ray	1956:1960	arg1	crystallography					1962:1976	X-ray crystallography	1956:1976	X-ray crystallography	1956:1976	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	9	3	gly	glycoproteins	1735:1747	arg1	glycoproteins					1735:1747	glycoproteins	1735:1747	glycoproteins	1735:1747	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	1	4	theme	new	97:99	arg1	method					101:106	A new method	95:106	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA),	95:228	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	6	5	theme	BCAM	1289:1292	arg1	analysis					1249:1256	detailed analysis	1240:1256	detailed analysis of ephrin-A5, GALNT10, PVR and BCAM	1240:1292	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	6	6	from	LDA	1093:1095	arg1	Data					1079:1082	Data	1079:1082	Data from the LDA and 3D structure analysis	1079:1121	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	9	7	theme	conformational	1709:1722	arg1	changes					1724:1730	conformational changes	1709:1730	conformational changes of glycoproteins	1709:1747	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	11	8	theme	nuclear	1979:1985	arg1	resonance					1996:2004	nuclear magnetic resonance	1979:2004	nuclear magnetic resonance spectroscopy	1979:2017	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	6	9	theme	PVR	1281:1283	arg1	analysis					1249:1256	detailed analysis	1240:1256	detailed analysis of ephrin-A5, GALNT10, PVR and BCAM	1240:1292	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	3	10	dep	N-deglycosylation	576:592	arg1	1					559:559	1	559:559	1	559:559	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	6	11	theme	GALNT10	1272:1278	arg1	analysis					1249:1256	detailed analysis	1240:1256	detailed analysis of ephrin-A5, GALNT10, PVR and BCAM	1240:1292	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	13	12	theme	structural	2394:2403	arg1	changes					2405:2411	PTMs-mediated structural changes	2380:2411	PTMs-mediated structural changes in complex proteomes	2380:2432	The LDA method presented here, can be applied to a range of pathophysiological conditions and expanded to investigate PTMs-mediated structural changes in complex proteomes.
34450331	2	13	theme	N-glycans	308:316	arg1	deglycosylation					289:303	deglycosylation	289:303	deglycosylation of N-glycans	289:316	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	1	14	theme	limited	193:199	arg1	assay					217:221	limited deglycosylation assay	193:221	limited deglycosylation assay (LDA)	193:227	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	1	14	theme	limited	193:199	arg1	LDA					224:226	LDA	224:226	LDA	224:226	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	11	15	theme	major	2049:2053	arg1	techniques					2055:2064	the major techniques	2045:2064	the major techniques applied to elucidate macromolecule structures	2045:2110	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	15	theme	major	2049:2053	arg1	techniques					2030:2039	cryoEM techniques	2023:2039	cryoEM techniques	2023:2039	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	15	theme	major	2049:2053	arg1	spectroscopy					2006:2017	nuclear magnetic resonance spectroscopy	1979:2017	nuclear magnetic resonance spectroscopy	1979:2017	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	15	theme	major	2049:2053	arg1	crystallography					1962:1976	X-ray crystallography	1956:1976	X-ray crystallography	1956:1976	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	6	16	theme	structural	1171:1180	arg1	changes					1182:1188	structural changes	1171:1188	structural changes in loops/turns upon ER stress	1171:1218	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	3	17	theme	MS-based	724:731	arg1	analysis					733:740	quantitative MS-based analysis	711:740	5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs)	708:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	2	18	theme	deglycosylation	289:303	arg1	rate					281:284	the differential rate	264:284	the differential rate of deglycosylation of N-glycans	264:316	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	19	theme	glycoprotein	519:530	arg1	conformation					532:543	the glycoprotein conformation	515:543	the glycoprotein conformation	515:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	8	20	theme	glycoprotein	1475:1486	arg1	changes					1499:1505	glycoprotein structural changes	1475:1505	glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases	1475:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	7	21	theme	treatment	1423:1431	arg1	regimes					1433:1439	controlled treatment regimes	1412:1439	controlled treatment regimes	1412:1439	These results show that LDA accurately reports on systems-wide conformational changes of glycoproteins induced under controlled treatment regimes.
34450331	11	22	theme	magnetic	1987:1994	arg1	resonance					1996:2004	nuclear magnetic resonance	1979:2004	nuclear magnetic resonance spectroscopy	1979:2017	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	3	23	gly	N-deglycosylation	576:592	arg1	peptides					769:776	formerly N-glycosylated peptides	745:776	formerly N-glycosylated peptides (FNGPs)	745:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	23	gly	N-deglycosylation	576:592	arg1	FNGPs					779:783	FNGPs	779:783	FNGPs	779:783	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	5	24	with	treatment	978:986	arg1	dithiothreitol					993:1006	dithiothreitol	993:1006	dithiothreitol	993:1006	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	3	25	theme	native	600:605	arg1	conditions					607:616	native conditions	600:616	native conditions	600:616	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	26	theme	N-glycosylated	754:767	arg1	peptides					769:776	formerly N-glycosylated peptides	745:776	formerly N-glycosylated peptides (FNGPs)	745:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	26	theme	N-glycosylated	754:767	arg1	FNGPs					779:783	FNGPs	779:783	FNGPs	779:783	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	1	27	gly	glycoproteins	147:159	arg1	glycoproteins					147:159	glycoproteins	147:159	glycoproteins	147:159	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	10	28	theme	site	1853:1856	arg1	activity					1905:1912	site and conformational-specific PNGase F enzymatic activity	1853:1912	site and conformational-specific PNGase F enzymatic activity	1853:1912	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	1	29	theme	conformational	121:134	arg1	changes					136:142	the conformational changes	117:142	the conformational changes of glycoproteins	117:159	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	7	30	theme	glycoproteins	1384:1396	arg1	changes					1373:1379	systems-wide conformational changes	1345:1379	systems-wide conformational changes of glycoproteins induced under controlled treatment regimes	1345:1439	These results show that LDA accurately reports on systems-wide conformational changes of glycoproteins induced under controlled treatment regimes.
34450331	6	31	theme	detailed	1240:1247	arg1	analysis					1249:1256	detailed analysis	1240:1256	detailed analysis of ephrin-A5, GALNT10, PVR and BCAM	1240:1292	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	12	32	theme	oligosaccharide	2156:2170	arg1	chains					2172:2177	the oligosaccharide chains	2152:2177	the oligosaccharide chains	2152:2177	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	0	33	theme	deglycosylation	72:86	arg1	assay					88:92	limited deglycosylation assay	64:92	limited deglycosylation assay	64:92	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.
34450331	10	34	theme	F	1893:1893	arg1	activity					1905:1912	site and conformational-specific PNGase F enzymatic activity	1853:1912	site and conformational-specific PNGase F enzymatic activity	1853:1912	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	8	35	theme	physiological	1527:1539	arg1	conditions					1564:1573	other physiological and pathophysiological conditions	1521:1573	other physiological and pathophysiological conditions relevant to acute and chronic diseases	1521:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	1	36	theme	systems-wide	166:177	arg1	scale					179:183	a systems-wide scale	164:183	a systems-wide scale	164:183	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	3	37	gly	N-glycosylated	754:767	arg1	peptides					769:776	formerly N-glycosylated peptides	745:776	formerly N-glycosylated peptides (FNGPs)	745:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	37	gly	N-glycosylated	754:767	arg1	FNGPs					779:783	FNGPs	779:783	FNGPs	779:783	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	8	38	theme	relevant	1575:1582	arg1	conditions					1564:1573	other physiological and pathophysiological conditions	1521:1573	other physiological and pathophysiological conditions relevant to acute and chronic diseases	1521:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	6	39	gly	glycoproteins	1135:1147	arg1	glycoproteins					1135:1147	glycoproteins	1135:1147	glycoproteins	1135:1147	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	2	40	theme	PNGase	385:390	arg1	F					382:382	N-glycosidase F	368:382	the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation	349:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	40	theme	PNGase	385:390	arg1	F					392:392	PNGase F	385:392	PNGase F	385:392	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	7	41	theme	conformational	1358:1371	arg1	changes					1373:1379	systems-wide conformational changes	1345:1379	systems-wide conformational changes of glycoproteins induced under controlled treatment regimes	1345:1439	These results show that LDA accurately reports on systems-wide conformational changes of glycoproteins induced under controlled treatment regimes.
34450331	2	42	from	presentation	441:452	arg1	conformation					532:543	the glycoprotein conformation	515:543	the glycoprotein conformation	515:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	42	from	presentation	441:452	arg1	surface					490:496	the protein surface	478:496	the protein surface	478:496	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	43	theme	F	382:382	arg1	enzyme					395:400	N-glycosidase F (PNGase F) enzyme	368:400	the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation	349:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	0	44	theme	Systems-wide	0:11	arg1	analysis					13:20	Systems-wide analysis	0:20	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.	0:93	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.
34450331	13	45	theme	pathophysiological	2322:2339	arg1	conditions					2341:2350	pathophysiological conditions	2322:2350	pathophysiological conditions	2322:2350	The LDA method presented here, can be applied to a range of pathophysiological conditions and expanded to investigate PTMs-mediated structural changes in complex proteomes.
34450331	8	46	theme	chronic	1597:1603	arg1	diseases					1605:1612	acute and chronic diseases	1587:1612	acute and chronic diseases	1587:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	9	47	theme	novel	1643:1647	arg1	method					1649:1654	a novel method	1641:1654	a novel method termed limited deglycosylation assay (LDA)	1641:1697	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	10	48	theme	current	1799:1805	arg1	toolbox					1807:1813	the current toolbox	1795:1813	the current toolbox of structural proteomics	1795:1838	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	5	49	theme	LLC-MK2	948:954	arg1	cells					967:971	LLC-MK2 epithelial cells	948:971	LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding	948:1076	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	2	50	from	measures	255:262	arg1	proteins					337:344	natively folded proteins	321:344	natively folded proteins	321:344	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	10	51	theme	quantitative	1931:1942	arg1	proteomics					1944:1953	large scale quantitative proteomics	1919:1953	large scale quantitative proteomics	1919:1953	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	6	52	from	changes	1182:1188	arg1	loops/turns					1193:1203	loops/turns	1193:1203	loops/turns	1193:1203	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	0	53	theme	conformational	38:51	arg1	changes					53:59	glycoprotein conformational changes	25:59	glycoprotein conformational changes	25:59	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.
34450331	5	54	theme	reticulum	1030:1038	arg1	stress					1040:1045	endoplasmic reticulum stress	1018:1045	endoplasmic reticulum stress	1018:1045	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	2	55	theme	spatial	433:439	arg1	presentation					441:452	their spatial presentation	427:452	their spatial presentation	427:452	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	8	56	from	changes	1499:1505	arg1	range					1512:1516	a range	1510:1516	a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases	1510:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	0	57	gly	glycoprotein	25:36	arg1	glycoprotein					25:36	glycoprotein conformational changes	25:59	glycoprotein conformational changes	25:59	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.
34450331	10	58	theme	scale	1925:1929	arg1	proteomics					1944:1953	large scale quantitative proteomics	1919:1953	large scale quantitative proteomics	1919:1953	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	2	59	theme	folded	330:335	arg1	proteins					337:344	natively folded proteins	321:344	natively folded proteins	321:344	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	7	60	from	reports	1334:1340	arg1	changes					1373:1379	systems-wide conformational changes	1345:1379	systems-wide conformational changes of glycoproteins induced under controlled treatment regimes	1345:1439	These results show that LDA accurately reports on systems-wide conformational changes of glycoproteins induced under controlled treatment regimes.
34450331	3	61	theme	glycopeptide	644:655	arg1	enrichment					657:666	3) glycopeptide enrichment	641:666	3) glycopeptide enrichment	641:666	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	4	62	dep	RNase	870:874	arg1	fetuin					882:887	fetuin	882:887	fetuin	882:887	LDA was initially developed and the experimental conditions optimized using bovine RNase B and fetuin.
34450331	4	62	dep	RNase	870:874	arg1	B					876:876	B	876:876	B	876:876	LDA was initially developed and the experimental conditions optimized using bovine RNase B and fetuin.
34450331	12	63	theme	chains	2172:2177	arg1	heterogeneity					2135:2147	heterogeneity	2135:2147	heterogeneity	2135:2147	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	12	63	theme	chains	2172:2177	arg1	size					2126:2129	size	2126:2129	size	2126:2129	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	6	64	theme	structure	1104:1112	arg1	analysis					1114:1121	the LDA and 3D structure analysis	1089:1121	analysis	1114:1121	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	2	65	gly	deglycosylation	289:303	arg1	N-glycans					308:316	N-glycans	308:316	N-glycans	308:316	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	66	theme	common	353:358	arg1	peptide					360:366	the common peptide	349:366	the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation	349:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	13	67	theme	LDA	2266:2268	arg1	method					2270:2275	The LDA method	2262:2275	The LDA method	2262:2275	The LDA method presented here, can be applied to a range of pathophysiological conditions and expanded to investigate PTMs-mediated structural changes in complex proteomes.
34450331	4	68	theme	bovine	863:868	arg1	RNase					870:874	bovine RNase B and fetuin	863:887	bovine RNase B and fetuin	863:887	LDA was initially developed and the experimental conditions optimized using bovine RNase B and fetuin.
34450331	10	69	theme	large	1919:1923	arg1	proteomics					1944:1953	large scale quantitative proteomics	1919:1953	large scale quantitative proteomics	1919:1953	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	5	70	from	cells	967:971	arg1	extracts					934:941	glycoprotein extracts	921:941	glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding	921:1076	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	3	71	dep	enrichment	657:666	arg1	3					641:641	3	641:641	3	641:641	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	6	72	theme	ER	1210:1211	arg1	stress					1213:1218	ER stress	1210:1218	ER stress	1210:1218	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	3	73	theme	quantitative	711:722	arg1	analysis					733:740	quantitative MS-based analysis	711:740	5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs)	708:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	2	74	theme	differential	268:279	arg1	rate					281:284	the differential rate	264:284	the differential rate of deglycosylation of N-glycans	264:316	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	8	75	gly	glycoprotein	1475:1486	arg1	glycoprotein					1475:1486	glycoprotein structural changes	1475:1505	glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases	1475:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	4	76	theme	experimental	823:834	arg1	conditions					836:845	and the experimental conditions	815:845	conditions	836:845	LDA was initially developed and the experimental conditions optimized using bovine RNase B and fetuin.
34450331	7	77	gly	glycoproteins	1384:1396	arg1	glycoproteins					1384:1396	glycoproteins	1384:1396	glycoproteins	1384:1396	These results show that LDA accurately reports on systems-wide conformational changes of glycoproteins induced under controlled treatment regimes.
34450331	9	78	theme	glycoproteins	1735:1747	arg1	changes					1724:1730	conformational changes	1709:1730	conformational changes of glycoproteins	1709:1747	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	3	79	theme	formerly	745:752	arg1	peptides					769:776	formerly N-glycosylated peptides	745:776	formerly N-glycosylated peptides (FNGPs)	745:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	79	theme	formerly	745:752	arg1	FNGPs					779:783	FNGPs	779:783	FNGPs	779:783	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	9	80	theme	limited	1663:1669	arg1	assay					1687:1691	limited deglycosylation assay	1663:1691	limited deglycosylation assay (LDA)	1663:1697	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	9	80	theme	limited	1663:1669	arg1	LDA					1694:1696	LDA	1694:1696	LDA	1694:1696	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	10	81	theme	proteomics	1829:1838	arg1	toolbox					1807:1813	the current toolbox	1795:1813	the current toolbox of structural proteomics	1795:1838	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	1	82	theme	deglycosylation	201:215	arg1	assay					217:221	limited deglycosylation assay	193:221	limited deglycosylation assay (LDA)	193:227	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	1	82	theme	deglycosylation	201:215	arg1	LDA					224:226	LDA	224:226	LDA	224:226	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	2	83	from	exposure	466:473	arg1	conformation					532:543	the glycoprotein conformation	515:543	the glycoprotein conformation	515:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	83	from	exposure	466:473	arg1	surface					490:496	the protein surface	478:496	the protein surface	478:496	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	84	gly	glycoprotein	519:530	arg1	glycoprotein					519:530	the glycoprotein conformation	515:543	the glycoprotein conformation	515:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	12	85	gly	glycoproteins	2247:2259	arg1	glycoproteins					2247:2259	glycoproteins	2247:2259	glycoproteins	2247:2259	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	10	86	theme	PNGase	1886:1891	arg1	F					1893:1893	conformational-specific PNGase F	1862:1893	conformational-specific PNGase F	1862:1893	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	6	87	theme	ephrin-A5	1261:1269	arg1	analysis					1249:1256	detailed analysis	1240:1256	detailed analysis of ephrin-A5, GALNT10, PVR and BCAM	1240:1292	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34450331	3	88	theme	protein-level	562:574	arg1	N-deglycosylation					576:592	protein-level N-deglycosylation	562:592	1) protein-level N-deglycosylation under native conditions	559:616	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	8	89	theme	pathophysiological	1545:1562	arg1	conditions					1564:1573	other physiological and pathophysiological conditions	1521:1573	other physiological and pathophysiological conditions relevant to acute and chronic diseases	1521:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	7	90	theme	controlled	1412:1421	arg1	regimes					1433:1439	controlled treatment regimes	1412:1439	controlled treatment regimes	1412:1439	These results show that LDA accurately reports on systems-wide conformational changes of glycoproteins induced under controlled treatment regimes.
34450331	12	91	theme	several	2185:2191	arg1	challenges					2193:2202	several challenges	2185:2202	several challenges to the applications of these techniques to glycoproteins	2185:2259	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	3	92	theme	peptides	769:776	arg1	enrichment					657:666	3) glycopeptide enrichment	641:666	3) glycopeptide enrichment	641:666	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	92	theme	peptides	769:776	arg1	digestion					630:638	trypsin digestion	622:638	2) trypsin digestion	619:638	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	92	theme	peptides	769:776	arg1	N-deglycosylation					686:702	4) peptide-level N-deglycosylation	669:702	4) peptide-level N-deglycosylation	669:702	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	92	theme	peptides	769:776	arg1	N-deglycosylation					576:592	protein-level N-deglycosylation	562:592	1) protein-level N-deglycosylation under native conditions	559:616	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	92	theme	peptides	769:776	arg1	analysis					733:740	quantitative MS-based analysis	711:740	5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs)	708:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	5	93	theme	protein	1059:1065	arg1	misfolding					1067:1076	protein misfolding	1059:1076	protein misfolding	1059:1076	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	11	94	theme	macromolecule	2087:2099	arg1	structures					2101:2110	macromolecule structures	2087:2110	macromolecule structures	2087:2110	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	13	95	theme	complex	2416:2422	arg1	proteomes					2424:2432	complex proteomes	2416:2432	complex proteomes	2416:2432	The LDA method presented here, can be applied to a range of pathophysiological conditions and expanded to investigate PTMs-mediated structural changes in complex proteomes.
34450331	8	96	theme	other	1521:1525	arg1	conditions					1564:1573	other physiological and pathophysiological conditions	1521:1573	other physiological and pathophysiological conditions relevant to acute and chronic diseases	1521:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	10	97	theme	enzymatic	1895:1903	arg1	activity					1905:1912	site and conformational-specific PNGase F enzymatic activity	1853:1912	site and conformational-specific PNGase F enzymatic activity	1853:1912	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	1	98	theme	glycoproteins	147:159	arg1	changes					136:142	the conformational changes	117:142	the conformational changes of glycoproteins	117:159	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	3	99	dep	analysis	733:740	arg1	5					708:708	5	708:708	5	708:708	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	13	100	theme	PTMs-mediated	2380:2392	arg1	changes					2405:2411	PTMs-mediated structural changes	2380:2411	PTMs-mediated structural changes in complex proteomes	2380:2432	The LDA method presented here, can be applied to a range of pathophysiological conditions and expanded to investigate PTMs-mediated structural changes in complex proteomes.
34450331	2	101	theme	solvent	458:464	arg1	exposure					466:473	solvent exposure	458:473	solvent exposure	458:473	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	8	102	theme	conditions	1564:1573	arg1	range					1512:1516	a range	1510:1516	a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases	1510:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	1	103	dep	method	101:106	arg1	probe					111:115	probe	111:115	to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA),	108:228	A new method to probe the conformational changes of glycoproteins on a systems-wide scale, termed limited deglycosylation assay (LDA), is described.
34450331	8	104	theme	structural	1488:1497	arg1	changes					1499:1505	glycoprotein structural changes	1475:1505	glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases	1475:1612	Thus, LDA opens avenues to study glycoprotein structural changes in a range of other physiological and pathophysiological conditions relevant to acute and chronic diseases.
34450331	13	105	from	changes	2405:2411	arg1	proteomes					2424:2432	complex proteomes	2416:2432	complex proteomes	2416:2432	The LDA method presented here, can be applied to a range of pathophysiological conditions and expanded to investigate PTMs-mediated structural changes in complex proteomes.
34450331	5	106	theme	epithelial	956:965	arg1	cells					967:971	LLC-MK2 epithelial cells	948:971	LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding	948:1076	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	10	107	theme	structural	1818:1827	arg1	proteomics					1829:1838	structural proteomics	1818:1838	structural proteomics	1818:1838	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	5	108	gly	glycoprotein	921:932	arg1	glycoprotein					921:932	glycoprotein extracts	921:941	glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding	921:1076	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	7	109	theme	systems-wide	1345:1356	arg1	changes					1373:1379	systems-wide conformational changes	1345:1379	systems-wide conformational changes of glycoproteins induced under controlled treatment regimes	1345:1439	These results show that LDA accurately reports on systems-wide conformational changes of glycoproteins induced under controlled treatment regimes.
34450331	2	110	theme	protein	482:488	arg1	surface					490:496	the protein surface	478:496	the protein surface	478:496	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	111	dep	peptide	360:366	arg1	enzyme					395:400	N-glycosidase F (PNGase F) enzyme	368:400	the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation	349:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	5	112	theme	glycoprotein	921:932	arg1	extracts					934:941	glycoprotein extracts	921:941	glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding	921:1076	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	9	113	theme	systems-wide	1754:1765	arg1	scale					1767:1771	a systems-wide scale	1752:1771	a systems-wide scale	1752:1771	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	2	114	theme	N-glycosidase	368:380	arg1	F					382:382	N-glycosidase F	368:382	the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation	349:543	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	2	114	theme	N-glycosidase	368:380	arg1	F					392:392	PNGase F	385:392	PNGase F	385:392	The method measures the differential rate of deglycosylation of N-glycans on natively folded proteins by the common peptide:N-glycosidase F (PNGase F) enzyme which in turn informs on their spatial presentation and solvent exposure on the protein surface hence ultimately the glycoprotein conformation.
34450331	0	115	theme	glycoprotein	25:36	arg1	changes					53:59	glycoprotein conformational changes	25:59	glycoprotein conformational changes	25:59	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.
34450331	13	116	theme	conditions	2341:2350	arg1	range					2313:2317	a range	2311:2317	a range of pathophysiological conditions	2311:2350	The LDA method presented here, can be applied to a range of pathophysiological conditions and expanded to investigate PTMs-mediated structural changes in complex proteomes.
34450331	0	117	theme	changes	53:59	arg1	analysis					13:20	Systems-wide analysis	0:20	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.	0:93	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.
34450331	3	118	dep	N-deglycosylation	686:702	arg1	4					669:669	4	669:669	4	669:669	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	12	119	theme	techniques	2233:2242	arg1	applications					2211:2222	the applications	2207:2222	the applications of these techniques to glycoproteins	2207:2259	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	5	120	theme	endoplasmic	1018:1028	arg1	reticulum					1030:1038	endoplasmic reticulum	1018:1038	endoplasmic reticulum stress	1018:1045	The method was then applied to glycoprotein extracts from LLC-MK2 epithelial cells upon treatment with dithiothreitol to induce endoplasmic reticulum stress and promote protein misfolding.
34450331	11	121	theme	resonance	1996:2004	arg1	techniques					2055:2064	the major techniques	2045:2064	the major techniques applied to elucidate macromolecule structures	2045:2110	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	121	theme	resonance	1996:2004	arg1	techniques					2030:2039	cryoEM techniques	2023:2039	cryoEM techniques	2023:2039	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	121	theme	resonance	1996:2004	arg1	spectroscopy					2006:2017	nuclear magnetic resonance spectroscopy	1979:2017	nuclear magnetic resonance spectroscopy	1979:2017	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	121	theme	resonance	1996:2004	arg1	crystallography					1962:1976	X-ray crystallography	1956:1976	X-ray crystallography	1956:1976	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	3	122	gly	N-deglycosylation	686:702	arg1	peptides					769:776	formerly N-glycosylated peptides	745:776	formerly N-glycosylated peptides (FNGPs)	745:784	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	122	gly	N-deglycosylation	686:702	arg1	FNGPs					779:783	FNGPs	779:783	FNGPs	779:783	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	123	theme	trypsin	622:628	arg1	digestion					630:638	trypsin digestion	622:638	2) trypsin digestion	619:638	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	11	124	theme	cryoEM	2023:2028	arg1	techniques					2055:2064	the major techniques	2045:2064	the major techniques applied to elucidate macromolecule structures	2045:2110	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	124	theme	cryoEM	2023:2028	arg1	crystallography					1962:1976	X-ray crystallography	1956:1976	X-ray crystallography	1956:1976	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	124	theme	cryoEM	2023:2028	arg1	spectroscopy					2006:2017	nuclear magnetic resonance spectroscopy	1979:2017	nuclear magnetic resonance spectroscopy	1979:2017	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	11	124	theme	cryoEM	2023:2028	arg1	techniques					2030:2039	cryoEM techniques	2023:2039	cryoEM techniques	2023:2039	X-ray crystallography, nuclear magnetic resonance spectroscopy and cryoEM techniques are the major techniques applied to elucidate macromolecule structures.
34450331	0	125	theme	limited	64:70	arg1	assay					88:92	limited deglycosylation assay	64:92	limited deglycosylation assay	64:92	Systems-wide analysis of glycoprotein conformational changes by limited deglycosylation assay.
34450331	12	126	gly	heterogeneity	2135:2147	arg1	chains					2172:2177	the oligosaccharide chains	2152:2177	the oligosaccharide chains	2152:2177	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	9	127	theme	deglycosylation	1671:1685	arg1	assay					1687:1691	limited deglycosylation assay	1663:1691	limited deglycosylation assay (LDA)	1663:1697	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	9	127	theme	deglycosylation	1671:1685	arg1	LDA					1694:1696	LDA	1694:1696	LDA	1694:1696	SIGNIFICANCE: We describe a novel method termed limited deglycosylation assay (LDA), to probe conformational changes of glycoproteins on a systems-wide scale.
34450331	10	128	theme	conformational-specific	1862:1884	arg1	F					1893:1893	conformational-specific PNGase F	1862:1893	conformational-specific PNGase F	1862:1893	This method improves the current toolbox of structural proteomics by combining site and conformational-specific PNGase F enzymatic activity with large scale quantitative proteomics.
34450331	12	129	dep	size	2126:2129	arg1	the					2122:2124	the	2122:2124	the	2122:2124	However, the size and heterogeneity of the oligosaccharide chains poses several challenges to the applications of these techniques to glycoproteins.
34450331	3	130	dep	digestion	630:638	arg1	2					619:619	2	619:619	2	619:619	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	131	gly	glycopeptide	644:655	arg2	glycopeptide					644:655	3) glycopeptide enrichment	641:666	3) glycopeptide enrichment	641:666	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	3	132	theme	peptide-level	672:684	arg1	N-deglycosylation					686:702	4) peptide-level N-deglycosylation	669:702	4) peptide-level N-deglycosylation	669:702	LDA involves 1) protein-level N-deglycosylation under native conditions, 2) trypsin digestion, 3) glycopeptide enrichment, 4) peptide-level N-deglycosylation and 5) quantitative MS-based analysis of formerly N-glycosylated peptides (FNGPs).
34450331	6	133	from	analysis	1114:1121	arg1	Data					1079:1082	Data	1079:1082	Data from the LDA and 3D structure analysis	1079:1121	Data from the LDA and 3D structure analysis showed that glycoproteins predominantly undergo structural changes in loops/turns upon ER stress as exemplified with detailed analysis of ephrin-A5, GALNT10, PVR and BCAM.
34117223	6	0	theme	glycan-binding	945:958	arg1	antibodies					1025:1034	selected anti-glycan antibodies	1004:1034	selected anti-glycan antibodies towards these O-GalNAc glycans	1004:1065	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	6	0	theme	glycan-binding	945:958	arg1	lectins					992:998	plant lectins	986:998	plant lectins	986:998	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	6	0	theme	glycan-binding	945:958	arg1	GBPs					970:973	GBPs	970:973	GBPs	970:973	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	6	0	theme	glycan-binding	945:958	arg1	proteins					960:967	glycan-binding proteins	945:967	glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans	945:1065	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	7	1	theme	colorectal	1176:1185	arg1	patients					1194:1201	colorectal cancer patients	1176:1201	colorectal cancer patients	1176:1201	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	1	2	theme	biological	146:155	arg1	growth					201:206	tumor growth	195:206	tumor growth	195:206	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	2	theme	biological	146:155	arg1	processes					174:182	diverse biological and pathological processes	138:182	diverse biological and pathological processes	138:182	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	2	theme	biological	146:155	arg1	progression					212:222	progression	212:222	progression	212:222	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	6	3	theme	Binding	920:926	arg1	specificities					928:940	Binding specificities	920:940	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans	920:1065	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	5	4	theme	O-GalNAc	780:787	arg1	glycans					789:795	83 O-GalNAc glycans	777:795	83 O-GalNAc glycans presenting various natural glycan epitopes	777:838	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	7	5	theme	cancer	1187:1192	arg1	patients					1194:1201	colorectal cancer patients	1176:1201	colorectal cancer patients	1176:1201	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	3	6	theme	diverse	536:542	arg1	glycans					553:559	structurally diverse O-GalNAc glycans	523:559	structurally diverse O-GalNAc glycans	523:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	4	7	theme	convergent	594:603	arg1	key					566:568	key	566:568	key	566:568	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	4	7	theme	convergent	594:603	arg1	assembly					605:612	the convergent assembly	590:612	the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks	590:676	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	7	8	from	controls	1215:1222	arg1	samples					1163:1169	Serum samples	1157:1169	Serum samples from colorectal cancer patients and healthy controls are assayed using the array	1157:1250	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	2	9	theme	synthetic	304:312	arg1	challenges					314:323	synthetic challenges	304:323	synthetic challenges	304:323	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	4	10	theme	O-GalNAc	617:624	arg1	cores					626:630	O-GalNAc cores 1-4 and 6	617:640	cores	626:630	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	2	11	contain	have	380:383	arg2	access					393:398	limited access	385:398	limited access to these compounds	385:417	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	2	11	contain	have	380:383	arg1	diversity					355:363	their inherent structural diversity	329:363	their inherent structural diversity	329:363	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	2	11	contain	have	380:383	arg1	challenges					314:323	synthetic challenges	304:323	synthetic challenges	304:323	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	7	12	theme	healthy	1207:1213	arg1	controls					1215:1222	healthy controls	1207:1222	healthy controls	1207:1222	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	2	13	theme	limited	385:391	arg1	access					393:398	limited access	385:398	limited access to these compounds	385:417	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	6	14	theme	anti-glycan	1013:1023	arg1	antibodies					1025:1034	selected anti-glycan antibodies	1004:1034	selected anti-glycan antibodies towards these O-GalNAc glycans	1004:1065	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	4	15	from	assembly	605:612	arg1	blocks					671:676	three chemical building blocks	647:676	three chemical building blocks	647:676	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	5	16	theme	glycan	824:829	arg1	epitopes					831:838	various natural glycan epitopes	808:838	various natural glycan epitopes	808:838	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	1	17	theme	O-GalNAc	78:85	arg1	glycans					87:93	O-GalNAc glycans	78:93	O-GalNAc glycans (or mucin O-glycans)	78:114	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	17	theme	O-GalNAc	78:85	arg1	O-glycans					105:113	mucin O-glycans	99:113	mucin O-glycans	99:113	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	5	18	theme	synthetic	883:891	arg1	microarray					908:917	a unique synthetic mucin O-glycan microarray	874:917	a unique synthetic mucin O-glycan microarray	874:917	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	1	19	theme	pathological	161:172	arg1	growth					201:206	tumor growth	195:206	tumor growth	195:206	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	19	theme	pathological	161:172	arg1	processes					174:182	diverse biological and pathological processes	138:182	diverse biological and pathological processes	138:182	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	19	theme	pathological	161:172	arg1	progression					212:222	progression	212:222	progression	212:222	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	7	20	theme	higher	1259:1264	arg1	bindings					1266:1273	higher bindings	1259:1273	higher bindings towards less common cores 3, 4, and 6	1259:1311	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	5	21	theme	glycans	789:795	arg1	total					768:772	A total	766:772	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes	766:838	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	2	22	theme	functional	281:290	arg1	studies					292:298	functional studies	281:298	functional studies	281:298	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	3	23	theme	chemoenzymatic	462:475	arg1	strategy					501:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy	438:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans	438:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	0	24	theme	modular	15:21	arg1	assembly					23:30	Chemoenzymatic modular assembly	0:30	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics	0:75	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.
34117223	7	25	theme	common	1288:1293	arg1	cores					1295:1299	less common cores 3, 4, and 6	1283:1311	less common cores 3, 4, and 6	1283:1311	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	2	26	theme	inherent	335:342	arg1	diversity					355:363	their inherent structural diversity	329:363	their inherent structural diversity	329:363	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	4	27	from	blocks	671:676	arg1	key					566:568	key	566:568	key	566:568	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	4	27	from	blocks	671:676	arg1	assembly					605:612	the convergent assembly	590:612	the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks	590:676	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	4	27	from	blocks	671:676	arg1	cores					626:630	O-GalNAc cores 1-4 and 6	617:640	cores	626:630	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	3	28	theme	efficient	441:449	arg1	strategy					501:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy	438:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans	438:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	0	29	theme	Chemoenzymatic	0:13	arg1	assembly					23:30	Chemoenzymatic modular assembly	0:30	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics	0:75	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.
34117223	6	30	theme	selected	1004:1011	arg1	antibodies					1025:1034	selected anti-glycan antibodies	1004:1034	selected anti-glycan antibodies towards these O-GalNAc glycans	1004:1065	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	4	31	theme	enzyme	750:755	arg1	modules					757:763	13 well-tailored enzyme modules	733:763	13 well-tailored enzyme modules	733:763	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	5	32	theme	mucin	893:897	arg1	microarray					908:917	a unique synthetic mucin O-glycan microarray	874:917	a unique synthetic mucin O-glycan microarray	874:917	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	6	33	from	applicability	1116:1128	arg1	O-glycomics					1144:1154	functional O-glycomics	1133:1154	functional O-glycomics	1133:1154	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	1	34	theme	mucin	99:103	arg1	glycans					87:93	O-GalNAc glycans	78:93	O-GalNAc glycans (or mucin O-glycans)	78:114	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	34	theme	mucin	99:103	arg1	O-glycans					105:113	mucin O-glycans	99:113	mucin O-glycans	99:113	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	35	theme	tumor	195:199	arg1	growth					201:206	tumor growth	195:206	tumor growth	195:206	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	5	36	used	used	857:860	arg2	total					768:772	A total	766:772	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes	766:838	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	6	37	theme	functional	1133:1142	arg1	O-glycomics					1144:1154	functional O-glycomics	1133:1154	functional O-glycomics	1133:1154	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	3	38	theme	CEMA	495:498	arg1	strategy					501:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy	438:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans	438:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	0	39	theme	glycans	44:50	arg1	assembly					23:30	Chemoenzymatic modular assembly	0:30	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics	0:75	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.
34117223	6	40	theme	plant	986:990	arg1	lectins					992:998	plant lectins	986:998	plant lectins	986:998	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	4	41	theme	building	662:669	arg1	blocks					671:676	three chemical building blocks	647:676	three chemical building blocks	647:676	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	2	42	theme	O-GalNAc	246:253	arg1	glycans					255:261	Structurally defined O-GalNAc glycans	225:261	Structurally defined O-GalNAc glycans	225:261	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	3	43	theme	modular	477:483	arg1	strategy					501:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy	438:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans	438:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	0	44	theme	O-GalNAc	35:42	arg1	glycans					44:50	O-GalNAc glycans	35:50	O-GalNAc glycans	35:50	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.
34117223	2	45	theme	defined	238:244	arg1	glycans					255:261	Structurally defined O-GalNAc glycans	225:261	Structurally defined O-GalNAc glycans	225:261	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	3	46	theme	assembly	485:492	arg1	strategy					501:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy	438:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans	438:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	0	47	theme	functional	56:65	arg1	glycomics					67:75	functional glycomics	56:75	functional glycomics	56:75	Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.
34117223	5	48	theme	O-glycan	899:906	arg1	microarray					908:917	a unique synthetic mucin O-glycan microarray	874:917	a unique synthetic mucin O-glycan microarray	874:917	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	3	49	theme	robust	455:460	arg1	strategy					501:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy	438:508	an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans	438:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	7	50	theme	abundant	1318:1325	arg1	cores					1327:1331	abundant cores 1 and 2	1318:1339	abundant cores 1 and 2	1318:1339	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	5	51	theme	natural	816:822	arg1	epitopes					831:838	various natural glycan epitopes	808:838	various natural glycan epitopes	808:838	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	7	52	from	patients	1194:1201	arg1	samples					1163:1169	Serum samples	1157:1169	Serum samples from colorectal cancer patients and healthy controls are assayed using the array	1157:1250	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	7	53	theme	Serum	1157:1161	arg1	samples					1163:1169	Serum samples	1157:1169	Serum samples from colorectal cancer patients and healthy controls are assayed using the array	1157:1250	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	7	54	theme	O-GalNAc	1366:1373	arg1	relationships					1401:1413	O-GalNAc glycan structure-activity relationships	1366:1413	O-GalNAc glycan structure-activity relationships	1366:1413	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	4	55	theme	cores	724:728	arg1	diversification					701:715	enzymatic diversification	691:715	enzymatic diversification of the cores by 13 well-tailored enzyme modules	691:763	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	4	56	theme	enzymatic	691:699	arg1	diversification					701:715	enzymatic diversification	691:715	enzymatic diversification of the cores by 13 well-tailored enzyme modules	691:763	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	1	57	theme	pivotal	121:127	arg1	roles					129:133	pivotal roles	121:133	pivotal roles	121:133	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	4	58	theme	well-tailored	736:748	arg1	modules					757:763	13 well-tailored enzyme modules	733:763	13 well-tailored enzyme modules	733:763	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	2	59	theme	structural	344:353	arg1	diversity					355:363	their inherent structural diversity	329:363	their inherent structural diversity	329:363	Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds.
34117223	4	60	theme	cores	626:630	arg1	key					566:568	key	566:568	key	566:568	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	4	60	theme	cores	626:630	arg1	assembly					605:612	the convergent assembly	590:612	the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks	590:676	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	4	61	theme	chemical	653:660	arg1	blocks					671:676	three chemical building blocks	647:676	three chemical building blocks	647:676	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	7	62	theme	glycan	1375:1380	arg1	relationships					1401:1413	O-GalNAc glycan structure-activity relationships	1366:1413	O-GalNAc glycan structure-activity relationships	1366:1413	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	3	63	theme	O-GalNAc	544:551	arg1	glycans					553:559	structurally diverse O-GalNAc glycans	523:559	structurally diverse O-GalNAc glycans	523:559	Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans.
34117223	5	64	theme	unique	876:881	arg1	microarray					908:917	a unique synthetic mucin O-glycan microarray	874:917	a unique synthetic mucin O-glycan microarray	874:917	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	4	65	theme	6	640:640	arg1	key					566:568	key	566:568	key	566:568	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	4	65	theme	6	640:640	arg1	assembly					605:612	the convergent assembly	590:612	the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks	590:676	The key to this strategy is the convergent assembly of O-GalNAc cores 1-4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules.
34117223	5	66	theme	various	808:814	arg1	epitopes					831:838	various natural glycan epitopes	808:838	various natural glycan epitopes	808:838	A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray.
34117223	6	67	theme	proteins	960:967	arg1	specificities					928:940	Binding specificities	920:940	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans	920:1065	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
34117223	7	68	theme	structure-activity	1382:1399	arg1	relationships					1401:1413	O-GalNAc glycan structure-activity relationships	1366:1413	O-GalNAc glycan structure-activity relationships	1366:1413	Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.
34117223	1	69	theme	diverse	138:144	arg1	growth					201:206	tumor growth	195:206	tumor growth	195:206	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	69	theme	diverse	138:144	arg1	processes					174:182	diverse biological and pathological processes	138:182	diverse biological and pathological processes	138:182	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	1	69	theme	diverse	138:144	arg1	progression					212:222	progression	212:222	progression	212:222	O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression.
34117223	6	70	theme	O-GalNAc	1050:1057	arg1	glycans					1059:1065	these O-GalNAc glycans	1044:1065	these O-GalNAc glycans	1044:1065	Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics.
33273015	8	0	theme	proMPO-to-MPO	1352:1364	arg1	maturation					1366:1375	proMPO-to-MPO maturation	1352:1375	proMPO-to-MPO maturation	1352:1375	We also show that proMPO-to-MPO maturation occurs during early/mid-stage granulopoiesis.
33273015	6	1	theme	unreported	1055:1064	arg1	monoprotomer					1080:1091	a previously unreported low-abundance monoprotomer	1042:1091	a previously unreported low-abundance monoprotomer	1042:1091	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	12	2	theme	novel	2180:2184	arg1	roles					2197:2201	novel functional roles	2180:2201	novel functional roles of MPO glycans	2180:2216	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	5	3	theme	molecular	747:755	arg1	basis					757:761	a molecular basis	745:761	a molecular basis of the site-specific nMPO glycosylation	745:801	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	6	4	theme	diprotomeric	918:929	arg1	nMPO					931:934	diprotomeric nMPO	918:934	diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants	918:1036	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	8	5	theme	early/mid-stage	1391:1405	arg1	granulopoiesis					1407:1420	early/mid-stage granulopoiesis	1391:1420	early/mid-stage granulopoiesis	1391:1420	We also show that proMPO-to-MPO maturation occurs during early/mid-stage granulopoiesis.
33273015	4	6	theme	Mass	443:446	arg1	spectrometry					448:459	Mass spectrometry	443:459	Mass spectrometry	443:459	Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans.
33273015	10	7	theme	ceruloplasmin-mediated	1882:1903	arg1	potential					1916:1924	ceruloplasmin-mediated inhibition potential	1882:1924	ceruloplasmin-mediated inhibition potential	1882:1924	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	5	8	theme	glycan	708:713	arg1	processing					715:724	the local glycan processing	698:724	the local glycan processing	698:724	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	9	9	theme	global	1437:1442	arg1	glycosylation					1448:1460	similar global MPO glycosylation	1429:1460	similar global MPO glycosylation	1429:1460	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	2	10	theme	functional	295:304	arg1	relevance					306:314	their functional relevance	289:314	their functional relevance	289:314	Complex carbohydrates decorate MPO at discrete sites, but their functional relevance remains elusive.
33273015	5	11	theme	Asn355/Asn391-glycosylation	574:600	arg1	sites					602:606	Asn355/Asn391-glycosylation sites	574:606	Asn355/Asn391-glycosylation sites	574:606	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	6	12	theme	polypeptide	1006:1016	arg1	variants					1029:1036	polypeptide truncation variants	1006:1036	polypeptide truncation variants	1006:1036	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	6	13	theme	significant	882:892	arg1	complexity					904:913	significant molecular complexity	882:913	significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants	882:1036	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	1	14	theme	oxidation	211:219	arg1	products					221:228	reactive oxidation products	202:228	reactive oxidation products	202:228	Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products.
33273015	5	15	theme	glycosylation	789:801	arg1	basis					757:761	a molecular basis	745:761	a molecular basis of the site-specific nMPO glycosylation	745:801	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	5	16	theme	located	640:646	arg1	sites					602:606	Asn355/Asn391-glycosylation sites	574:606	Asn355/Asn391-glycosylation sites	574:606	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	4	17	theme	under-processed	512:526	arg1	glycans					548:554	both characteristic under-processed and hyper-truncated glycans	492:554	both characteristic under-processed and hyper-truncated glycans	492:554	Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans.
33273015	5	18	dep	sites	602:606	arg1	the					570:572	the	570:572	the	570:572	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	7	19	theme	neutrophils	1180:1190	arg1	profiling					1107:1115	Longitudinal profiling	1094:1115	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils	1094:1190	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation.
33273015	1	20	theme	essential	132:140	arg1	roles					142:146	essential roles	132:146	essential roles	132:146	Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products.
33273015	5	21	theme	site-specific	770:782	arg1	glycosylation					789:801	the site-specific nMPO glycosylation	766:801	the site-specific nMPO glycosylation	766:801	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	5	22	from	zone	672:675	arg1	located					640:646	located	640:646	located	640:646	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	0	23	theme	neutrophil	68:77	arg1	myeloperoxidase					87:101	neutrophil granule myeloperoxidase	68:101	neutrophil granule myeloperoxidase	68:101	Hyper-truncated Asn355- and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase.
33273015	9	24	theme	elevated	1539:1546	arg1	hyper-truncation					1555:1570	elevated glycan hyper-truncation	1539:1570	elevated glycan hyper-truncation	1539:1570	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	5	25	theme	Asn323-/Asn483-glycans	616:637	arg1	Occlusion					557:565	Occlusion	557:565	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone,	557:676	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	0	26	theme	myeloperoxidase	87:101	arg1	activity					56:63	the activity	52:63	the activity of neutrophil granule myeloperoxidase	52:101	Hyper-truncated Asn355- and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase.
33273015	9	27	from	populations	1647:1657	arg1	activities					1609:1618	higher enzyme activities	1595:1618	higher enzyme activities of MPO in distinct granule populations	1595:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	5	28	gly	Asn355/Asn391-glycosylation	574:600	arg2	sites					602:606	Asn355/Asn391-glycosylation sites	574:606	Asn355/Asn391-glycosylation sites	574:606	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	10	29	theme	Enzymatic	1660:1668	arg1	trimming					1670:1677	Enzymatic trimming	1660:1677	Enzymatic trimming of the Asn355-/Asn391-glycans	1660:1707	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	4	30	theme	hyper-truncated	532:546	arg1	glycans					548:554	both characteristic under-processed and hyper-truncated glycans	492:554	both characteristic under-processed and hyper-truncated glycans	492:554	Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans.
33273015	10	31	theme	hyper-truncated	1771:1785	arg1	glycans					1787:1793	hyper-truncated glycans	1771:1793	hyper-truncated glycans	1771:1793	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	9	32	from	MPO	1623:1625	arg1	populations					1647:1657	distinct granule populations	1630:1657	distinct granule populations	1630:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	5	33	theme	dimerisation	659:670	arg1	zone					672:675	the MPO dimerisation zone	651:675	the MPO dimerisation zone	651:675	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	0	34	theme	Hyper-truncated	0:14	arg1	Asn355-					16:22	Hyper-truncated Asn355-	0:22	Hyper-truncated Asn355-	0:22	Hyper-truncated Asn355- and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase.
33273015	9	35	theme	enzyme	1602:1607	arg1	activities					1609:1618	higher enzyme activities	1595:1618	higher enzyme activities of MPO in distinct granule populations	1595:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	9	36	from	activities	1609:1618	arg1	populations					1647:1657	distinct granule populations	1630:1657	distinct granule populations	1630:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	3	37	theme	neutrophil	420:429	arg1	nMPO					436:439	nMPO	436:439	nMPO	436:439	To this end, we have characterised the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO).
33273015	3	37	theme	neutrophil	420:429	arg1	MPO					431:433	neutrophil MPO	420:433	neutrophil MPO (nMPO)	420:440	To this end, we have characterised the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO).
33273015	6	38	theme	glycopeptide	850:861	arg1	profiling					863:871	glycopeptide profiling	850:871	glycopeptide profiling	850:871	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	9	39	theme	granule	1639:1645	arg1	populations					1647:1657	distinct granule populations	1630:1657	distinct granule populations	1630:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	12	40	theme	glycans	2210:2216	arg1	roles					2197:2201	novel functional roles	2180:2201	novel functional roles of MPO glycans	2180:2216	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	10	41	theme	increased	1823:1831	arg1	stability					1841:1849	increased thermal stability	1823:1849	increased thermal stability	1823:1849	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	2	42	theme	Complex	231:237	arg1	carbohydrates					239:251	Complex carbohydrates	231:251	Complex carbohydrates	231:251	Complex carbohydrates decorate MPO at discrete sites, but their functional relevance remains elusive.
33273015	12	43	theme	new	2229:2231	arg1	insight					2233:2239	new insight	2229:2239	new insight into neutrophil-mediated immunity	2229:2273	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	6	44	theme	heterogeneous	949:961	arg1	glycosylation					963:975	heterogeneous glycosylation	949:975	heterogeneous glycosylation	949:975	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	6	45	theme	low-abundance	1066:1078	arg1	monoprotomer					1080:1091	a previously unreported low-abundance monoprotomer	1042:1091	a previously unreported low-abundance monoprotomer	1042:1091	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	12	46	theme	functional	2186:2195	arg1	roles					2197:2201	novel functional roles	2180:2201	novel functional roles of MPO glycans	2180:2216	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	10	47	theme	polypeptide	1852:1862	arg1	accessibility					1864:1876	polypeptide accessibility	1852:1876	polypeptide accessibility	1852:1876	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	6	48	theme	mass	811:814	arg1	spectrometry					816:827	Native mass spectrometry	804:827	Native mass spectrometry	804:827	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	12	49	theme	comprehensive	2146:2158	arg1	approach					2160:2167	an innovative and comprehensive approach	2128:2167	an innovative and comprehensive approach	2128:2167	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	10	50	theme	relative	1926:1933	arg1	stability					1841:1849	increased thermal stability	1823:1849	increased thermal stability	1823:1849	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	9	51	theme	MPO	1444:1446	arg1	glycosylation					1448:1460	similar global MPO glycosylation	1429:1460	similar global MPO glycosylation	1429:1460	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	6	52	theme	nMPO	931:934	arg1	monoprotomer					1080:1091	a previously unreported low-abundance monoprotomer	1042:1091	a previously unreported low-abundance monoprotomer	1042:1091	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	6	52	theme	nMPO	931:934	arg1	complexity					904:913	significant molecular complexity	882:913	significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants	882:1036	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	10	53	theme	inhibition	1905:1914	arg1	potential					1916:1924	ceruloplasmin-mediated inhibition potential	1882:1924	ceruloplasmin-mediated inhibition potential	1882:1924	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	11	54	theme	MPO-ceruloplasmin	2043:2059	arg1	interface					2061:2069	the MPO-ceruloplasmin interface	2039:2069	the MPO-ceruloplasmin interface	2039:2069	Finally, molecular modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition.
33273015	5	55	theme	local	702:706	arg1	processing					715:724	the local glycan processing	698:724	the local glycan processing	698:724	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	9	56	theme	similar	1429:1435	arg1	glycosylation					1448:1460	similar global MPO glycosylation	1429:1460	similar global MPO glycosylation	1429:1460	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	6	57	theme	truncation	1018:1027	arg1	variants					1029:1036	polypeptide truncation variants	1006:1036	polypeptide truncation variants	1006:1036	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	6	58	theme	molecular	894:902	arg1	complexity					904:913	significant molecular complexity	882:913	significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants	882:1036	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	5	59	theme	sites	602:606	arg1	Occlusion					557:565	Occlusion	557:565	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone,	557:676	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	1	60	theme	reactive	202:209	arg1	products					221:228	reactive oxidation products	202:228	reactive oxidation products	202:228	Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products.
33273015	12	61	theme	innovative	2131:2140	arg1	approach					2160:2167	an innovative and comprehensive approach	2128:2167	an innovative and comprehensive approach	2128:2167	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	10	62	theme	native	1938:1943	arg1	nMPO					1945:1948	native nMPO	1938:1948	native nMPO	1938:1948	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	10	63	theme	Asn355-/Asn391-glycans	1686:1707	arg1	trimming					1670:1677	Enzymatic trimming	1660:1677	Enzymatic trimming of the Asn355-/Asn391-glycans	1660:1707	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	5	64	theme	nMPO	784:787	arg1	glycosylation					789:801	the site-specific nMPO glycosylation	766:801	the site-specific nMPO glycosylation	766:801	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	1	65	theme	products	221:228	arg1	generation					188:197	the generation	184:197	the generation of reactive oxidation products	184:228	Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products.
33273015	4	66	theme	characteristic	497:510	arg1	glycans					548:554	both characteristic under-processed and hyper-truncated glycans	492:554	both characteristic under-processed and hyper-truncated glycans	492:554	Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans.
33273015	2	67	theme	discrete	269:276	arg1	sites					278:282	discrete sites	269:282	discrete sites	269:282	Complex carbohydrates decorate MPO at discrete sites, but their functional relevance remains elusive.
33273015	10	68	contain	carrying	1762:1769	arg1	nMPO					1757:1760	nMPO	1757:1760	nMPO carrying hyper-truncated glycans at these positions	1757:1812	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	10	68	contain	carrying	1762:1769	arg2	glycans					1787:1793	hyper-truncated glycans	1771:1793	hyper-truncated glycans	1771:1793	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	9	69	theme	conserved	1498:1506	arg1	Asn355-/Asn391-sites					1508:1527	the conserved Asn355-/Asn391-sites	1494:1527	the conserved Asn355-/Asn391-sites	1494:1527	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	5	70	theme	MPO	655:657	arg1	zone					672:675	the MPO dimerisation zone	651:675	the MPO dimerisation zone	651:675	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	0	71	theme	granule	79:85	arg1	myeloperoxidase					87:101	neutrophil granule myeloperoxidase	68:101	neutrophil granule myeloperoxidase	68:101	Hyper-truncated Asn355- and Asn391-glycans modulate the activity of neutrophil granule myeloperoxidase.
33273015	7	72	theme	pathogen-stimulated	1160:1178	arg1	neutrophils					1180:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation.
33273015	1	73	theme	neutrophil-mediated	151:169	arg1	immunity					171:178	neutrophil-mediated immunity	151:178	neutrophil-mediated immunity	151:178	Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products.
33273015	9	74	theme	glycan	1548:1553	arg1	hyper-truncation					1555:1570	elevated glycan hyper-truncation	1539:1570	elevated glycan hyper-truncation	1539:1570	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	7	75	theme	granule-separated	1138:1154	arg1	neutrophils					1180:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation.
33273015	6	76	gly	glycopeptide	850:861	arg2	glycopeptide					850:861	glycopeptide profiling	850:871	glycopeptide profiling	850:871	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	7	77	theme	mature	1130:1135	arg1	neutrophils					1180:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation.
33273015	11	78	theme	molecular	1960:1968	arg1	modelling					1970:1978	molecular modelling	1960:1978	molecular modelling	1960:1978	Finally, molecular modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition.
33273015	10	79	theme	activity	1727:1734	arg1	gain					1736:1739	the activity gain	1723:1739	the activity gain	1723:1739	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	6	80	theme	Native	804:809	arg1	spectrometry					816:827	Native mass spectrometry	804:827	Native mass spectrometry	804:827	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	7	81	theme	maturing	1120:1127	arg1	neutrophils					1180:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	maturing, mature, granule-separated and pathogen-stimulated neutrophils	1120:1190	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation.
33273015	3	82	theme	structure-biosynthesis-activity	372:402	arg1	relationship					404:415	the structure-biosynthesis-activity relationship	368:415	the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO)	368:440	To this end, we have characterised the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO).
33273015	4	83	contain	carries	484:490	arg1	nMPO					479:482	nMPO	479:482	nMPO	479:482	Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans.
33273015	4	83	contain	carries	484:490	arg2	glycans					548:554	both characteristic under-processed and hyper-truncated glycans	492:554	both characteristic under-processed and hyper-truncated glycans	492:554	Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans.
33273015	9	84	theme	higher	1595:1600	arg1	activities					1609:1618	higher enzyme activities	1595:1618	higher enzyme activities of MPO in distinct granule populations	1595:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	12	85	theme	neutrophil-mediated	2246:2264	arg1	immunity					2266:2273	neutrophil-mediated immunity	2246:2273	neutrophil-mediated immunity	2246:2273	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	3	86	theme	MPO	431:433	arg1	relationship					404:415	the structure-biosynthesis-activity relationship	368:415	the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO)	368:440	To this end, we have characterised the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO).
33273015	9	87	theme	MPO	1623:1625	arg1	activities					1609:1618	higher enzyme activities	1595:1618	higher enzyme activities of MPO in distinct granule populations	1595:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	5	88	from	located	640:646	arg1	zone					672:675	the MPO dimerisation zone	651:675	the MPO dimerisation zone	651:675	Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation.
33273015	9	89	theme	distinct	1630:1637	arg1	populations					1647:1657	distinct granule populations	1630:1657	distinct granule populations	1630:1657	While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations.
33273015	10	90	theme	thermal	1833:1839	arg1	stability					1841:1849	increased thermal stability	1823:1849	increased thermal stability	1823:1849	Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility and ceruloplasmin-mediated inhibition potential relative to native nMPO.
33273015	7	91	theme	Longitudinal	1094:1105	arg1	profiling					1107:1115	Longitudinal profiling	1094:1115	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils	1094:1190	Longitudinal profiling of maturing, mature, granule-separated and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation.
33273015	12	92	theme	MPO	2206:2208	arg1	glycans					2210:2216	MPO glycans	2206:2216	MPO glycans	2206:2216	Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity.
33273015	11	93	theme	uninterrupted	2088:2100	arg1	inhibition					2102:2111	uninterrupted inhibition	2088:2111	uninterrupted inhibition	2088:2111	Finally, molecular modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition.
33273015	6	94	theme	mass	830:833	arg1	photometry					835:844	mass photometry	830:844	mass photometry	830:844	Native mass spectrometry, mass photometry and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants and a previously unreported low-abundance monoprotomer.
33273015	11	95	theme	hyper-truncated	1994:2008	arg1	Asn355-glycans					2010:2023	hyper-truncated Asn355-glycans	1994:2023	hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface	1994:2069	Finally, molecular modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition.
33606939	0	0	from	Shielding	15:23	arg1	Protein					70:76	Lassa Virus Envelop Protein	50:76	Lassa Virus Envelop Protein	50:76	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	7	1	theme	simulation	1144:1153	arg1	results					1155:1161	the simulation results	1140:1161	the simulation results	1140:1161	We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods.
33606939	5	2	theme	protein	916:922	arg1	dynamics					924:931	protein dynamics	916:931	protein dynamics	916:931	The results show that glycosylation nonuniformly shields the surface of the complex and only marginally affects protein dynamics.
33606939	8	3	theme	structural	1266:1275	arg1	environment					1277:1287	the rich structural environment	1257:1287	the rich structural environment of glycans	1257:1298	The results emphasize the rich structural environment of glycans and demonstrate that shielding is not merely envelopment by a uniform blanket of sugars.
33606939	2	4	theme	effects	352:358	arg1	investigation					330:342	the investigation	326:342	the investigation of such effects	326:358	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	8	5	theme	glycans	1292:1298	arg1	environment					1277:1287	the rich structural environment	1257:1287	the rich structural environment of glycans	1257:1298	The results emphasize the rich structural environment of glycans and demonstrate that shielding is not merely envelopment by a uniform blanket of sugars.
33606939	3	6	theme	antibody	691:698	arg1	response					700:707	the antibody response	687:707	the antibody response	687:707	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	3	7	theme	atomistic	509:517	arg1	model					519:523	an atomistic model	506:523	an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus	506:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	4	8	theme	interactions	771:782	arg1	interactions					771:782	interactions	771:782	interactions	771:782	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	4	8	theme	interactions	771:782	arg1	conformations					753:765	conformations	753:765	conformations	753:765	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	4	8	theme	interactions	771:782	arg1	variety					742:748	the variety	738:748	the variety of conformations and interactions of surface glycans	738:801	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	3	9	theme	protein	558:564	arg1	complex					566:572	a fully glycosylated envelope protein complex	528:572	a fully glycosylated envelope protein complex of the Lassa virus	528:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	9	10	theme	glycans	1485:1491	arg1	properties					1471:1480	otherwise elusive structural properties	1442:1480	otherwise elusive structural properties of glycans	1442:1491	This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.
33606939	6	11	with	interaction	982:992	arg1	residues					1007:1014	protein residues	999:1014	protein residues	999:1014	The glycans gather in distinct clusters through interaction with protein residues, and only a few regions are left accessible by an antibody.
33606939	3	12	theme	glycosylated	536:547	arg1	complex					566:572	a fully glycosylated envelope protein complex	528:572	a fully glycosylated envelope protein complex of the Lassa virus	528:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	7	13	theme	epitope	1207:1213	arg1	prediction					1215:1224	structure-based epitope prediction	1191:1224	structure-based epitope prediction	1191:1224	We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods.
33606939	4	14	theme	surface	787:793	arg1	glycans					795:801	surface glycans	787:801	surface glycans	787:801	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	9	15	theme	neutralizing	1510:1521	arg1	developments					1532:1543	neutralizing antibody developments	1510:1543	neutralizing antibody developments	1510:1543	This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.
33606939	8	16	theme	sugars	1381:1386	arg1	blanket					1370:1376	a uniform blanket	1360:1376	a uniform blanket of sugars	1360:1386	The results emphasize the rich structural environment of glycans and demonstrate that shielding is not merely envelopment by a uniform blanket of sugars.
33606939	3	17	from	impact	658:663	arg1	response					700:707	the antibody response	687:707	the antibody response	687:707	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	0	18	from	Epitopes	38:45	arg1	Protein					70:76	Lassa Virus Envelop Protein	50:76	Lassa Virus Envelop Protein	50:76	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	8	19	theme	rich	1261:1264	arg1	environment					1277:1287	the rich structural environment	1257:1287	the rich structural environment of glycans	1257:1298	The results emphasize the rich structural environment of glycans and demonstrate that shielding is not merely envelopment by a uniform blanket of sugars.
33606939	4	20	theme	glycans	795:801	arg1	interactions					771:782	interactions	771:782	interactions	771:782	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	4	20	theme	glycans	795:801	arg1	conformations					753:765	conformations	753:765	conformations	753:765	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	0	21	theme	Cluster	7:13	arg1	Shielding					15:23	Glycan Cluster Shielding and Antibody Epitopes	0:45	Shielding	15:23	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	7	22	theme	known	1102:1106	arg1	epitopes					1116:1123	known protein epitopes	1102:1123	known protein epitopes	1102:1123	We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods.
33606939	3	23	theme	complex	566:572	arg1	model					519:523	an atomistic model	506:523	an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus	506:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	2	24	theme	huge	379:382	arg1	range					384:388	the huge range	375:388	the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility	375:488	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	0	25	theme	Glycan	0:5	arg1	Shielding					15:23	Glycan Cluster Shielding and Antibody Epitopes	0:45	Shielding	15:23	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	7	26	theme	protein	1108:1114	arg1	epitopes					1116:1123	known protein epitopes	1102:1123	known protein epitopes	1102:1123	We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods.
33606939	9	27	theme	antibody	1523:1530	arg1	developments					1532:1543	neutralizing antibody developments	1510:1543	neutralizing antibody developments	1510:1543	This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.
33606939	2	28	gly	glycosylation	242:254	arg1	antibody					303:310	the antibody response	299:319	the antibody response	299:319	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	2	28	gly	glycosylation	242:254	arg1	proteins					265:272	viral proteins	259:272	viral proteins	259:272	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	6	29	theme	protein	999:1005	arg1	residues					1007:1014	protein residues	999:1014	protein residues	999:1014	The glycans gather in distinct clusters through interaction with protein residues, and only a few regions are left accessible by an antibody.
33606939	5	30	gly	glycosylation	826:838	arg1	protein					916:922	protein dynamics	916:931	protein dynamics	916:931	The results show that glycosylation nonuniformly shields the surface of the complex and only marginally affects protein dynamics.
33606939	3	31	theme	envelope	549:556	arg1	complex					566:572	a fully glycosylated envelope protein complex	528:572	a fully glycosylated envelope protein complex of the Lassa virus	528:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	3	32	theme	virus	587:591	arg1	complex					566:572	a fully glycosylated envelope protein complex	528:572	a fully glycosylated envelope protein complex of the Lassa virus	528:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	2	33	theme	surface	424:430	arg1	glycans					432:438	surface glycans	424:438	surface glycans through their inherent complexity and flexibility	424:488	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	2	34	theme	antibody	303:310	arg1	response					312:319	the antibody response	299:319	the antibody response	299:319	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	2	35	theme	interactions	408:419	arg1	range					384:388	the huge range	375:388	the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility	375:488	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	7	36	theme	sequence-	1177:1185	arg1	methods					1226:1232	sequence- and structure-based epitope prediction methods	1177:1232	sequence- and structure-based epitope prediction methods	1177:1232	We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods.
33606939	2	37	theme	extensive	232:240	arg1	glycosylation					242:254	The extensive glycosylation	228:254	The extensive glycosylation of viral proteins	228:272	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	0	38	theme	Antibody	29:36	arg1	Epitopes					38:45	Glycan Cluster Shielding and Antibody Epitopes	0:45	Epitopes	38:45	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	2	39	theme	glycans	432:438	arg1	interactions					408:419	interactions	408:419	interactions	408:419	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	2	39	theme	glycans	432:438	arg1	structures					393:402	structures	393:402	structures	393:402	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	2	40	theme	structures	393:402	arg1	range					384:388	the huge range	375:388	the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility	375:488	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	0	41	theme	Lassa	50:54	arg1	Protein					70:76	Lassa Virus Envelop Protein	50:76	Lassa Virus Envelop Protein	50:76	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	9	42	theme	molecular	1410:1418	arg1	basis					1420:1424	a molecular basis	1408:1424	a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments	1408:1543	This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.
33606939	2	43	theme	such	347:350	arg1	effects					352:358	such effects	347:358	such effects	347:358	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	2	44	theme	inherent	454:461	arg1	complexity					463:472	their inherent complexity	448:472	their inherent complexity	448:472	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	6	45	theme	distinct	956:963	arg1	clusters					965:972	distinct clusters	956:972	distinct clusters	956:972	The glycans gather in distinct clusters through interaction with protein residues, and only a few regions are left accessible by an antibody.
33606939	3	46	theme	glycans	676:682	arg1	impact					658:663	the impact	654:663	the impact of surface glycans on the antibody response	654:707	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	3	47	theme	Lassa	581:585	arg1	virus					587:591	the Lassa virus	577:591	the Lassa virus	577:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	1	48	theme	antiviral	106:114	arg1	antibody					127:134	an antiviral monoclonal antibody	103:134	an antiviral monoclonal antibody	103:134	An understanding of how an antiviral monoclonal antibody recognizes its target is vital for the development of neutralizing antibodies and vaccines.
33606939	7	49	theme	structure-based	1191:1205	arg1	prediction					1215:1224	structure-based epitope prediction	1191:1224	structure-based epitope prediction	1191:1224	We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods.
33606939	3	50	theme	dynamics	617:624	arg1	simulations					626:636	molecular dynamics simulations	607:636	molecular dynamics simulations	607:636	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	2	51	theme	proteins	265:272	arg1	glycosylation					242:254	The extensive glycosylation	228:254	The extensive glycosylation of viral proteins	228:272	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	1	52	theme	monoclonal	116:125	arg1	antibody					127:134	an antiviral monoclonal antibody	103:134	an antiviral monoclonal antibody	103:134	An understanding of how an antiviral monoclonal antibody recognizes its target is vital for the development of neutralizing antibodies and vaccines.
33606939	4	53	theme	conformations	753:765	arg1	interactions					771:782	interactions	771:782	interactions	771:782	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	4	53	theme	conformations	753:765	arg1	conformations					753:765	conformations	753:765	conformations	753:765	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	4	53	theme	conformations	753:765	arg1	variety					742:748	the variety	738:748	the variety of conformations and interactions of surface glycans	738:801	The simulations attested to the variety of conformations and interactions of surface glycans.
33606939	2	54	theme	viral	259:263	arg1	proteins					265:272	viral proteins	259:272	viral proteins	259:272	The extensive glycosylation of viral proteins almost certainly affects the antibody response, but the investigation of such effects is hampered by the huge range of structures and interactions of surface glycans through their inherent complexity and flexibility.
33606939	8	55	theme	uniform	1362:1368	arg1	blanket					1370:1376	a uniform blanket	1360:1376	a uniform blanket of sugars	1360:1386	The results emphasize the rich structural environment of glycans and demonstrate that shielding is not merely envelopment by a uniform blanket of sugars.
33606939	0	56	theme	Envelop	62:68	arg1	Protein					70:76	Lassa Virus Envelop Protein	50:76	Lassa Virus Envelop Protein	50:76	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	3	57	theme	surface	668:674	arg1	glycans					676:682	surface glycans	668:682	surface glycans	668:682	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	3	58	gly	glycosylated	536:547	arg1	complex					566:572	a fully glycosylated envelope protein complex	528:572	a fully glycosylated envelope protein complex of the Lassa virus	528:591	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	5	59	theme	complex	880:886	arg1	surface					865:871	the surface	861:871	the surface of the complex	861:886	The results show that glycosylation nonuniformly shields the surface of the complex and only marginally affects protein dynamics.
33606939	9	60	theme	elusive	1452:1458	arg1	properties					1471:1480	otherwise elusive structural properties	1442:1480	otherwise elusive structural properties of glycans	1442:1491	This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.
33606939	0	61	theme	Virus	56:60	arg1	Protein					70:76	Lassa Virus Envelop Protein	50:76	Lassa Virus Envelop Protein	50:76	Glycan Cluster Shielding and Antibody Epitopes on Lassa Virus Envelop Protein.
33606939	3	62	theme	molecular	607:615	arg1	simulations					626:636	molecular dynamics simulations	607:636	molecular dynamics simulations	607:636	Here, we built an atomistic model of a fully glycosylated envelope protein complex of the Lassa virus and performed molecular dynamics simulations to characterize the impact of surface glycans on the antibody response.
33606939	7	63	theme	prediction	1215:1224	arg1	methods					1226:1232	sequence- and structure-based epitope prediction methods	1177:1232	sequence- and structure-based epitope prediction methods	1177:1232	We successfully recovered known protein epitopes by integrating the simulation results with existing sequence- and structure-based epitope prediction methods.
33606939	9	64	theme	structural	1460:1469	arg1	properties					1471:1480	otherwise elusive structural properties	1442:1480	otherwise elusive structural properties of glycans	1442:1491	This work provides a molecular basis for integrating otherwise elusive structural properties of glycans into vaccine and neutralizing antibody developments.
33540792	6	0	theme	skin	844:847	arg1	function					857:864	skin barrier function	844:864	skin barrier function towards molecules	844:882	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	8	1	contain	had	1093:1095	arg1	Fish					1045:1048	Fish	1045:1048	Fish subjected to both chronic and acute stress	1045:1091	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	8	1	contain	had	1093:1095	arg2	proportion					1110:1119	an increased proportion	1097:1119	an increased proportion of large O-glycan structures	1097:1148	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	4	2	theme	acute	645:649	arg1	stress					651:656	acute stress	645:656	acute stress 24 h	645:661	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	6	3	theme	second	827:832	arg1	sampling					834:841	the second sampling	823:841	the second sampling	823:841	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	6	4	theme	LD	922:923	arg1	Papp					932:935	Papp	932:935	Papp	932:935	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	6	4	theme	LD	922:923	arg1	group					925:929	the LD group	918:929	the LD group (Papp mannitol; p < 0.01)	918:955	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	7	5	theme	chromatography-mass	965:983	arg1	spectrometry					985:996	Liquid chromatography-mass spectrometry	958:996	Liquid chromatography-mass spectrometry	958:996	Liquid chromatography-mass spectrometry revealed 81 O-glycan structures from the skin.
33540792	3	6	from	changes	506:512	arg1	response					517:524	response	517:524	response to acute and chronic stress	517:552	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	8	7	theme	chronic	1068:1074	arg1	stress					1086:1091	both chronic and acute stress	1063:1091	both chronic and acute stress	1063:1091	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	10	8	theme	glycosylation	1337:1349	arg1	changes					1351:1357	glycosylation changes	1337:1357	glycosylation changes	1337:1357	Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
33540792	2	9	theme	mucin	264:268	arg1	glycosylation					270:282	Host mucin glycosylation	259:282	Host mucin glycosylation	259:282	Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function.
33540792	0	10	theme	Core	89:92	arg1	O-Glycans					96:104	Core 1 O-Glycans	89:104	Core 1 O-Glycans	89:104	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	11	from	α2-3	49:52	arg1	Mucins					114:119	Skin Mucins	109:119	Skin Mucins	109:119	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	11	from	α2-3	49:52	arg1	Salmon					133:138	Atlantic Salmon	124:138	Atlantic Salmon	124:138	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	11	from	α2-3	49:52	arg1	salar					147:151	Salmo salar	141:151	Salmo salar	141:151	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	1	12	gly	glycosylated	218:229	arg1	mucins					231:236	highly glycosylated mucins	211:236	highly glycosylated mucins	211:236	The skin barrier consists of mucus, primarily comprising highly glycosylated mucins, and the epithelium.
33540792	2	13	theme	Host	259:262	arg1	glycosylation					270:282	Host mucin glycosylation	259:282	Host mucin glycosylation	259:282	Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function.
33540792	2	14	with	interactions	292:303	arg1	pathogens					310:318	pathogens	310:318	pathogens	310:318	Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function.
33540792	8	15	theme	acute	1080:1084	arg1	stress					1086:1091	both chronic and acute stress	1063:1091	both chronic and acute stress	1063:1091	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	4	16	theme	24	658:659	arg1	h					661:661	h	661:661	h	661:661	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	5	17	theme	secondary	768:776	arg1	responses					785:793	primary and secondary stress responses	756:793	primary and secondary stress responses	756:793	Blood parameters indicated primary and secondary stress responses at both sampling points.
33540792	3	18	theme	acute	529:533	arg1	stress					547:552	acute and chronic stress	529:552	acute and chronic stress	529:552	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	3	19	theme	barrier	426:432	arg1	function					434:441	Atlantic salmon skin barrier function	405:441	Atlantic salmon skin barrier function	405:441	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	8	20	theme	large	1124:1128	arg1	structures					1139:1148	large O-glycan structures	1124:1148	large O-glycan structures	1124:1148	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	9	21	theme	stress	1221:1226	arg1	potential					1194:1202	potential	1194:1202	potential	1194:1202	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	9	21	theme	stress	1221:1226	arg1	indicators					1207:1216	indicators	1207:1216	indicators	1207:1216	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	7	22	theme	O-glycan	1010:1017	arg1	structures					1019:1028	81 O-glycan structures	1007:1028	81 O-glycan structures from the skin	1007:1042	Liquid chromatography-mass spectrometry revealed 81 O-glycan structures from the skin.
33540792	9	23	contain	have	1189:1192	arg1	changes					1181:1187	the O-glycan changes	1168:1187	the O-glycan changes	1168:1187	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	9	23	contain	have	1189:1192	arg2	indicators					1207:1216	indicators	1207:1216	indicators	1207:1216	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	9	23	contain	have	1189:1192	arg1	four					1160:1163	four	1160:1163	four	1160:1163	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	9	23	contain	have	1189:1192	arg2	potential					1194:1202	potential	1194:1202	potential	1194:1202	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	3	24	theme	chronic	450:456	arg1	stress					458:463	chronic stress	450:463	chronic stress (high density)	450:478	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	3	24	theme	chronic	450:456	arg1	density					471:477	high density	466:477	high density	466:477	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	5	25	theme	Blood	729:733	arg1	parameters					735:744	Blood parameters	729:744	Blood parameters	729:744	Blood parameters indicated primary and secondary stress responses at both sampling points.
33540792	6	26	dep	Papp	932:935	arg1	<					949:949	p < 0.01	947:954	p < 0.01	947:954	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	6	26	dep	Papp	932:935	arg1	mannitol					937:944	mannitol	937:944	Papp mannitol	932:944	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	1	27	theme	skin	158:161	arg1	barrier					163:169	The skin barrier	154:169	The skin barrier	154:169	The skin barrier consists of mucus, primarily comprising highly glycosylated mucins, and the epithelium.
33540792	10	28	theme	barrier	1308:1314	arg1	function					1316:1323	skin barrier function	1303:1323	skin barrier function	1303:1323	Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
33540792	2	29	theme	barrier	370:376	arg1	function					378:385	impaired epithelial barrier function	350:385	impaired epithelial barrier function	350:385	Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function.
33540792	0	30	theme	Barrier	20:26	arg1	Function					28:35	Skin Barrier Function	15:35	Skin Barrier Function	15:35	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	7	31	theme	Liquid	958:963	arg1	spectrometry					985:996	Liquid chromatography-mass spectrometry	958:996	Liquid chromatography-mass spectrometry	958:996	Liquid chromatography-mass spectrometry revealed 81 O-glycan structures from the skin.
33540792	10	32	theme	skin	1303:1306	arg1	function					1316:1323	skin barrier function	1303:1323	skin barrier function	1303:1323	Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
33540792	6	33	theme	p	947:947	arg1	<					949:949	p < 0.01	947:954	p < 0.01	947:954	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	4	34	dep	HD	610:611	arg1	kg/m3					620:624	50-80 kg/m3	614:624	HD: 50-80 kg/m3	610:624	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	3	35	theme	high	466:469	arg1	stress					458:463	chronic stress	450:463	chronic stress (high density)	450:478	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	3	35	theme	high	466:469	arg1	density					471:477	high density	466:477	high density	466:477	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	0	36	theme	Skin	15:18	arg1	Function					28:35	Skin Barrier Function	15:35	Skin Barrier Function	15:35	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	37	theme	Skin	109:112	arg1	Mucins					114:119	Skin Mucins	109:119	Skin Mucins	109:119	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	4	38	theme	high	594:597	arg1	densities					599:607	high densities	594:607	high densities (HD: 50-80 kg/m3)	594:625	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	3	39	theme	salmon	414:419	arg1	function					434:441	Atlantic salmon skin barrier function	405:441	Atlantic salmon skin barrier function	405:441	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	9	40	theme	combined	1248:1255	arg1	stress					1275:1280	the combined chronic and acute stress	1244:1280	the combined chronic and acute stress	1244:1280	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	0	41	theme	Atlantic	124:131	arg1	Salmon					133:138	Atlantic Salmon	124:138	Atlantic Salmon	124:138	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	41	theme	Atlantic	124:131	arg1	salar					147:151	Salmo salar	141:151	Salmo salar	141:151	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	4	42	dep	LD	573:574	arg1	kg/m3					583:587	14-30 kg/m3	577:587	LD: 14-30 kg/m3	573:587	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	0	43	dep	α2-3	49:52	arg1	Acid					80:83	Linked N-Acetylneuraminic Acid	54:83	Linked N-Acetylneuraminic Acid	54:83	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	10	44	with	interactions	1396:1407	arg1	pathogens					1414:1422	pathogens	1414:1422	pathogens	1414:1422	Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
33540792	5	45	theme	stress	778:783	arg1	responses					785:793	primary and secondary stress responses	756:793	primary and secondary stress responses	756:793	Blood parameters indicated primary and secondary stress responses at both sampling points.
33540792	3	46	theme	skin	421:424	arg1	function					434:441	Atlantic salmon skin barrier function	405:441	Atlantic salmon skin barrier function	405:441	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	9	47	theme	chronic	1257:1263	arg1	stress					1275:1280	the combined chronic and acute stress	1244:1280	the combined chronic and acute stress	1244:1280	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	5	48	theme	sampling	803:810	arg1	points					812:817	both sampling points	798:817	both sampling points	798:817	Blood parameters indicated primary and secondary stress responses at both sampling points.
33540792	8	49	theme	increased	1100:1108	arg1	proportion					1110:1119	an increased proportion	1097:1119	an increased proportion of large O-glycan structures	1097:1148	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	3	50	from	stress	458:463	arg1	response					517:524	response	517:524	response to acute and chronic stress	517:552	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	8	51	theme	O-glycan	1130:1137	arg1	structures					1139:1148	large O-glycan structures	1124:1148	large O-glycan structures	1124:1148	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	5	52	theme	primary	756:762	arg1	responses					785:793	primary and secondary stress responses	756:793	primary and secondary stress responses	756:793	Blood parameters indicated primary and secondary stress responses at both sampling points.
33540792	4	53	dep	low	568:570	arg1	LD					573:574	LD	573:574	LD: 14-30 kg/m3	573:587	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	4	54	dep	densities	599:607	arg1	HD					610:611	HD	610:611	HD: 50-80 kg/m3	610:624	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	3	55	theme	mucin	484:488	arg1	changes					506:512	mucin O-glycosylation changes	484:512	mucin O-glycosylation changes in response to acute and chronic stress	484:552	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	3	56	theme	Atlantic	405:412	arg1	salmon					414:419	Atlantic salmon	405:419	Atlantic salmon skin barrier function	405:441	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	9	57	theme	acute	1269:1273	arg1	stress					1275:1280	the combined chronic and acute stress	1244:1280	the combined chronic and acute stress	1244:1280	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	9	58	theme	changes	1181:1187	arg1	changes					1181:1187	the O-glycan changes	1168:1187	the O-glycan changes	1168:1187	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	9	58	theme	changes	1181:1187	arg1	four					1160:1163	four	1160:1163	four	1160:1163	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	3	59	theme	O-glycosylation	490:504	arg1	changes					506:512	mucin O-glycosylation changes	484:512	mucin O-glycosylation changes in response to acute and chronic stress	484:552	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	7	60	from	skin	1039:1042	arg1	structures					1019:1028	81 O-glycan structures	1007:1028	81 O-glycan structures from the skin	1007:1042	Liquid chromatography-mass spectrometry revealed 81 O-glycan structures from the skin.
33540792	0	61	from	O-Glycans	96:104	arg1	Mucins					114:119	Skin Mucins	109:119	Skin Mucins	109:119	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	61	from	O-Glycans	96:104	arg1	Salmon					133:138	Atlantic Salmon	124:138	Atlantic Salmon	124:138	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	61	from	O-Glycans	96:104	arg1	salar					147:151	Salmo salar	141:151	Salmo salar	141:151	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	62	theme	Salmo	141:145	arg1	Salmon					133:138	Atlantic Salmon	124:138	Atlantic Salmon	124:138	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	0	62	theme	Salmo	141:145	arg1	salar					147:151	Salmo salar	141:151	Salmo salar	141:151	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	3	63	theme	chronic	539:545	arg1	stress					547:552	acute and chronic stress	529:552	acute and chronic stress	529:552	We characterized Atlantic salmon skin barrier function during chronic stress (high density) and mucin O-glycosylation changes in response to acute and chronic stress.
33540792	10	64	contain	have	1366:1369	arg1	changes					1351:1357	glycosylation changes	1337:1357	glycosylation changes	1337:1357	Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
33540792	10	64	contain	have	1366:1369	arg2	potential					1371:1379	potential	1371:1379	potential to both affect interactions with pathogens and serve as stress indicators	1371:1453	Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
33540792	4	65	theme	h	661:661	arg1	stress					651:656	acute stress	645:656	acute stress 24 h	645:661	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	0	66	theme	N-Acetylneuraminic	61:78	arg1	Acid					80:83	Linked N-Acetylneuraminic Acid	54:83	Linked N-Acetylneuraminic Acid	54:83	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	9	67	theme	O-glycan	1172:1179	arg1	changes					1181:1187	the O-glycan changes	1168:1187	the O-glycan changes	1168:1187	Overall, four of the O-glycan changes have potential as indicators of stress, especially for the combined chronic and acute stress.
33540792	2	68	theme	epithelial	359:368	arg1	function					378:385	impaired epithelial barrier function	350:385	impaired epithelial barrier function	350:385	Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function.
33540792	8	69	theme	structures	1139:1148	arg1	proportion					1110:1119	an increased proportion	1097:1119	an increased proportion of large O-glycan structures	1097:1148	Fish subjected to both chronic and acute stress had an increased proportion of large O-glycan structures.
33540792	10	70	theme	stress	1437:1442	arg1	indicators					1444:1453	stress indicators	1437:1453	stress indicators	1437:1453	Stress thus impairs skin barrier function and induces glycosylation changes, which have potential to both affect interactions with pathogens and serve as stress indicators.
33540792	0	71	theme	Linked	54:59	arg1	Acid					80:83	Linked N-Acetylneuraminic Acid	54:83	Linked N-Acetylneuraminic Acid	54:83	Stress Impairs Skin Barrier Function and Induces α2-3 Linked N-Acetylneuraminic Acid and Core 1 O-Glycans on Skin Mucins in Atlantic Salmon, Salmo salar.
33540792	6	72	theme	barrier	849:855	arg1	function					857:864	skin barrier function	844:864	skin barrier function towards molecules	844:882	At the second sampling, skin barrier function towards molecules was reduced in the HD compared to the LD group (Papp mannitol; p < 0.01).
33540792	4	73	theme	experiment	717:726	arg1	start					704:708	start	704:708	start of the experiment	704:726	Fish held at low (LD: 14-30 kg/m3) and high densities (HD: 50-80 kg/m3) were subjected to acute stress 24 h before sampling at 17 and 21 weeks after start of the experiment.
33540792	2	74	theme	impaired	350:357	arg1	function					378:385	impaired epithelial barrier function	350:385	impaired epithelial barrier function	350:385	Host mucin glycosylation governs interactions with pathogens and stress is associated with impaired epithelial barrier function.
33540792	1	75	theme	glycosylated	218:229	arg1	mucins					231:236	highly glycosylated mucins	211:236	highly glycosylated mucins	211:236	The skin barrier consists of mucus, primarily comprising highly glycosylated mucins, and the epithelium.
33578083	2	0	theme	distinct	616:623	arg1	mass					625:628	each distinct mass	611:628	each distinct mass	611:628	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	1	theme	single	365:370	arg1	experiment					390:399	a single mass spectrometry experiment	363:399	a single mass spectrometry experiment	363:399	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	1	2	theme	posttranslational	252:268	arg1	modifications					270:282	smaller posttranslational modifications	244:282	smaller posttranslational modifications	244:282	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	6	3	theme	glycan	1400:1405	arg1	"					1416:1416	glycan "wildcard"	1400:1416	glycan "wildcard"	1400:1416	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	5	4	theme	m/z	1135:1137	arg1	peaks					1139:1143	m/z peaks	1135:1143	m/z peaks	1135:1143	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	3	5	theme	labeling	929:936	arg1	peaks					949:953	labeling diagnostic peaks	929:953	labeling diagnostic peaks	929:953	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	4	6	theme	search	1045:1050	arg1	program					1052:1058	a glycoproteomics search program	1027:1058	a glycoproteomics search program	1027:1058	Here, we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues.
33578083	4	6	theme	search	1045:1050	arg1	Byonic					1019:1024	Byonic	1019:1024	Byonic	1019:1024	Here, we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues.
33578083	7	7	theme	user-specified	1635:1648	arg1	annotations					1655:1665	user-specified peak annotations	1635:1665	user-specified peak annotations from user-defined posttranslational modifications	1635:1715	Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications.
33578083	5	8	theme	filtering	1114:1122	arg1	spectra					1124:1130	filtering spectra	1114:1130	filtering spectra	1114:1130	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	9	theme	274.092	1272:1278	arg1	three					1243:1247	three	1243:1247	three	1243:1247	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	9	theme	274.092	1272:1278	arg1	366.139					1313:1319	366.139	1313:1319	366.139	1313:1319	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	9	theme	274.092	1272:1278	arg1	274.092					1272:1278	274.092	1272:1278	274.092	1272:1278	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	9	theme	274.092	1272:1278	arg1	all					1337:1339	all	1337:1339	all	1337:1339	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	9	theme	274.092	1272:1278	arg1	204.087					1252:1258	204.087	1252:1258	204.087	1252:1258	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	2	10	theme	Exact	285:289	arg1	elucidation					302:312	Exact structural elucidation	285:312	Exact structural elucidation of glycans	285:323	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	1	11	theme	bioinformatics	159:172	arg1	challenges					174:183	analytical and bioinformatics challenges	144:183	challenges	174:183	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	3	12	theme	tandem	958:963	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	2	13	theme	glycans	317:323	arg1	elucidation					302:312	Exact structural elucidation	285:312	Exact structural elucidation of glycans	285:323	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	14	theme	glycan	550:555	arg1	composition					557:567	glycan composition	550:567	glycan composition	550:567	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	8	15	gly	glycosylated	1863:1874	arg1	neuropeptides					1876:1888	glycosylated neuropeptides	1863:1888	glycosylated neuropeptides from rat brain	1863:1903	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	8	16	theme	glycosylated	1863:1874	arg1	neuropeptides					1876:1888	glycosylated neuropeptides	1863:1888	glycosylated neuropeptides from rat brain	1863:1903	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	1	17	theme	unmodified	207:216	arg1	peptides					218:225	unmodified peptides	207:225	unmodified peptides	207:225	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	6	18	theme	mass	1477:1480	arg1	range					1482:1486	a user-set mass range	1466:1486	a user-set mass range	1466:1486	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	1	19	theme	protein	111:117	arg1	samples					119:125	peptide or digested protein samples	91:125	samples	119:125	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	8	20	theme	software	1758:1765	arg1	features					1767:1774	these new software features	1748:1774	these new software features	1748:1774	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	8	21	from	glycopeptides	1811:1823	arg1	data					1847:1850	publicly available data	1828:1850	publicly available data	1828:1850	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	3	22	from	glycans	858:864	arg1	database					893:900	the initial glycan database	874:900	the initial glycan database	874:900	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	23	theme	total	806:810	arg1	spectra					812:818	the total spectra	802:818	the total spectra	802:818	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	24	theme	finding	740:746	arg1	spectra					761:767	finding glycopeptide spectra	740:767	finding glycopeptide spectra when they are a tiny fraction of the total spectra	740:818	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	25	with	spectra	761:767	arg1	glycans					858:864	unanticipated glycans	844:864	unanticipated glycans	844:864	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	26	theme	assigning	821:829	arg1	spectra					831:837	assigning spectra	821:837	assigning spectra with unanticipated glycans, not in the initial glycan database	821:900	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	6	27	theme	unspecified	1442:1452	arg1	mass					1454:1457	an unspecified mass	1439:1457	an unspecified mass within a user-set mass range	1439:1486	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	1	28	theme	analytical	144:153	arg1	challenges					174:183	analytical and bioinformatics challenges	144:183	challenges	174:183	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	3	29	theme	spectra	812:818	arg1	fraction					790:797	a tiny fraction	783:797	a tiny fraction of the total spectra	783:818	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	29	theme	spectra	812:818	arg1	they					774:777	they	774:777	they	774:777	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	7	30	from	modifications	1703:1715	arg1	annotations					1655:1665	user-specified peak annotations	1635:1665	user-specified peak annotations from user-defined posttranslational modifications	1635:1715	Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications.
33578083	6	31	theme	O-linked	1511:1518	arg1	glycans					1520:1526	O-linked glycans	1511:1526	O-linked glycans	1511:1526	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	3	32	from	challenges	728:737	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	5	33	with	spectra	1186:1192	arg1	peaks					1210:1214	diagnostic peaks	1199:1214	diagnostic peaks	1199:1214	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	3	34	with	challenges	728:737	arg1	glycans					858:864	unanticipated glycans	844:864	unanticipated glycans	844:864	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	6	35	dep	"	1416:1416	arg1	search					1418:1423	search	1418:1423	search	1418:1423	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	2	36	theme	HexNAc	637:642	arg1	Hex					646:648	HexNAc(2)Hex(5)	637:651	HexNAc(2)Hex(5)	637:651	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	37	theme	reasonable	407:416	arg1	that					521:524	that	521:524	that	521:524	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	37	theme	reasonable	407:416	arg1	level					418:422	a reasonable level	405:422	a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools,	405:516	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	7	38	theme	posttranslational	1685:1701	arg1	modifications					1703:1715	user-defined posttranslational modifications	1672:1715	user-defined posttranslational modifications	1672:1715	Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications.
33578083	5	39	theme	366.139	1313:1319	arg1	three					1243:1247	three	1243:1247	three	1243:1247	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	39	theme	366.139	1313:1319	arg1	366.139					1313:1319	366.139	1313:1319	366.139	1313:1319	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	39	theme	366.139	1313:1319	arg1	274.092					1272:1278	274.092	1272:1278	274.092	1272:1278	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	39	theme	366.139	1313:1319	arg1	all					1337:1339	all	1337:1339	all	1337:1339	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	39	theme	366.139	1313:1319	arg1	204.087					1252:1258	204.087	1252:1258	204.087	1252:1258	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	0	40	theme	Peak	0:3	arg1	Filtering					5:13	Peak Filtering	0:13	Peak Filtering	0:13	Peak Filtering, Peak Annotation, and Wildcard Search for Glycoproteomics.
33578083	5	41	with	NeuAc	1284:1288	arg1	loss					1302:1305	water loss	1296:1305	water loss	1296:1305	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	2	42	theme	mass	453:456	arg1	spectrometry					458:469	tandem mass spectrometry	446:469	tandem mass spectrometry	446:469	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	43	theme	glycopeptide	489:500	arg1	tools					511:515	several glycopeptide software tools	481:515	several glycopeptide software tools	481:515	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	6	44	theme	unanticipated	1567:1579	arg1	glycans					1581:1587	unanticipated glycans	1567:1587	unanticipated glycans	1567:1587	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	2	45	gly	glycopeptide	489:500	arg2	glycopeptide					489:500	glycopeptide	489:500	glycopeptide	489:500	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	6	46	theme	spectra	1554:1560	arg1	assignment					1540:1549	assignment	1540:1549	assignment of spectra with unanticipated glycans	1540:1587	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	8	47	theme	rat	1895:1897	arg1	brain					1899:1903	rat brain	1895:1903	rat brain	1895:1903	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	7	48	theme	user-defined	1672:1683	arg1	modifications					1703:1715	user-defined posttranslational modifications	1672:1715	user-defined posttranslational modifications	1672:1715	Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications.
33578083	3	49	theme	glycan	886:891	arg1	database					893:900	the initial glycan database	874:900	the initial glycan database	874:900	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	4	50	theme	recent	996:1001	arg1	improvements					1003:1014	recent improvements	996:1014	recent improvements to Byonic, a glycoproteomics search program, that address these three issues	996:1091	Here, we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues.
33578083	5	51	theme	mass	1354:1357	arg1	tolerance					1359:1367	a set mass tolerance	1348:1367	a set mass tolerance	1348:1367	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	3	52	with	finding	907:913	arg1	glycans					858:864	unanticipated glycans	844:864	unanticipated glycans	844:864	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	1	53	with	peptides	230:237	arg1	modifications					270:282	smaller posttranslational modifications	244:282	smaller posttranslational modifications	244:282	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	2	54	theme	experiment	390:399	arg1	capability					349:358	the capability	345:358	the capability of a single mass spectrometry experiment	345:399	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	6	55	link	O-linked	1511:1518	arg1	glycans					1520:1526	O-linked glycans	1511:1526	O-linked glycans	1511:1526	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	3	56	with	scoring	916:922	arg1	glycans					858:864	unanticipated glycans	844:864	unanticipated glycans	844:864	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	1	57	with	peptides	218:225	arg1	modifications					270:282	smaller posttranslational modifications	244:282	smaller posttranslational modifications	244:282	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	2	58	theme	mass	372:375	arg1	experiment					390:399	a single mass spectrometry experiment	363:399	a single mass spectrometry experiment	363:399	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	1	59	theme	smaller	244:250	arg1	modifications					270:282	smaller posttranslational modifications	244:282	smaller posttranslational modifications	244:282	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	3	60	theme	diagnostic	938:947	arg1	peaks					949:953	labeling diagnostic peaks	929:953	labeling diagnostic peaks	929:953	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	61	from	peaks	949:953	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	7	62	theme	peak	1650:1653	arg1	annotations					1655:1665	user-specified peak annotations	1635:1665	user-specified peak annotations from user-defined posttranslational modifications	1635:1715	Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications.
33578083	5	63	theme	water	1296:1300	arg1	loss					1302:1305	water loss	1296:1305	water loss	1296:1305	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	2	64	theme	monosaccharides	592:606	arg1	number					582:587	the number	578:587	the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5	578:668	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	65	theme	structural	291:300	arg1	elucidation					302:312	Exact structural elucidation	285:312	Exact structural elucidation of glycans	285:323	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	3	66	theme	mass	965:968	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	67	from	spectra	831:837	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	1	68	theme	challenges	174:183	arg1	number					134:139	a number	132:139	a number of analytical and bioinformatics challenges	132:183	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	2	69	theme	mass	625:628	arg1	monosaccharides					592:606	monosaccharides	592:606	monosaccharides	592:606	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	3	70	theme	glycopeptide	700:711	arg1	analysis					713:720	glycopeptide analysis	700:720	glycopeptide analysis	700:720	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	4	71	theme	glycoproteomics	1029:1043	arg1	program					1052:1058	a glycoproteomics search program	1027:1058	a glycoproteomics search program	1027:1058	Here, we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues.
33578083	4	71	theme	glycoproteomics	1029:1043	arg1	Byonic					1019:1024	Byonic	1019:1024	Byonic	1019:1024	Here, we discuss recent improvements to Byonic, a glycoproteomics search program, that address these three issues.
33578083	8	72	theme	new	1754:1756	arg1	features					1767:1774	these new software features	1748:1774	these new software features	1748:1774	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	3	73	from	spectra	761:767	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	1	74	theme	digested	102:109	arg1	samples					119:125	peptide or digested protein samples	91:125	samples	119:125	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	6	75	theme	user-set	1468:1475	arg1	range					1482:1486	a user-set mass range	1466:1486	a user-set mass range	1466:1486	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	8	76	theme	features	1767:1774	arg1	utility					1737:1743	the utility	1733:1743	the utility of these new software features	1733:1774	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	2	77	dep	Hex	646:648	arg1	2					644:644	2	644:644	2	644:644	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	77	dep	Hex	646:648	arg1	e.g.					631:634	e.g.	631:634	e.g.	631:634	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	3	78	gly	glycopeptide	748:759	arg2	glycopeptide					748:759	finding glycopeptide spectra	740:767	finding glycopeptide spectra when they are a tiny fraction of the total spectra	740:818	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	8	79	gly	glycopeptides	1811:1823	arg2	glycopeptides					1811:1823	previously unrecognized glycopeptides	1787:1823	previously unrecognized glycopeptides	1787:1823	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	8	79	gly	glycopeptides	1811:1823	arg2	neuropeptides					1876:1888	glycosylated neuropeptides	1863:1888	glycosylated neuropeptides from rat brain	1863:1903	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	3	80	theme	glycopeptide	748:759	arg1	spectra					761:767	finding glycopeptide spectra	740:767	finding glycopeptide spectra when they are a tiny fraction of the total spectra	740:818	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	8	81	theme	unrecognized	1798:1809	arg1	neuropeptides					1876:1888	glycosylated neuropeptides	1863:1888	glycosylated neuropeptides from rat brain	1863:1903	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	8	81	theme	unrecognized	1798:1809	arg1	glycopeptides					1811:1823	previously unrecognized glycopeptides	1787:1823	previously unrecognized glycopeptides	1787:1823	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	8	82	from	brain	1899:1903	arg1	neuropeptides					1876:1888	glycosylated neuropeptides	1863:1888	glycosylated neuropeptides from rat brain	1863:1903	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	2	83	theme	software	502:509	arg1	tools					511:515	several glycopeptide software tools	481:515	several glycopeptide software tools	481:515	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	3	84	theme	tiny	785:788	arg1	fraction					790:797	a tiny fraction	783:797	a tiny fraction of the total spectra	783:818	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	84	theme	tiny	785:788	arg1	they					774:777	they	774:777	they	774:777	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	85	with	spectra	831:837	arg1	glycans					858:864	unanticipated glycans	844:864	unanticipated glycans	844:864	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	2	86	theme	peptide	529:535	arg1	sequence					537:544	peptide sequence	529:544	peptide sequence	529:544	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	3	87	gly	glycopeptide	700:711	arg2	glycopeptide					700:711	glycopeptide analysis	700:720	glycopeptide analysis	700:720	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	8	88	theme	available	1837:1845	arg1	data					1847:1850	publicly available data	1828:1850	publicly available data	1828:1850	We demonstrate the utility of these new software features by finding previously unrecognized glycopeptides in publicly available data, including glycosylated neuropeptides from rat brain.
33578083	3	89	from	finding	907:913	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	90	theme	unanticipated	844:856	arg1	glycans					858:864	unanticipated glycans	844:864	unanticipated glycans	844:864	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	3	91	from	scoring	916:922	arg1	spectra					970:976	tandem mass spectra	958:976	tandem mass spectra	958:976	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	5	92	theme	diagnostic	1199:1208	arg1	peaks					1210:1214	diagnostic peaks	1199:1214	diagnostic peaks	1199:1214	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	0	93	theme	Peak	16:19	arg1	Annotation					21:30	Peak Annotation	16:30	Peak Annotation	16:30	Peak Filtering, Peak Annotation, and Wildcard Search for Glycoproteomics.
33578083	6	94	theme	wildcard	1408:1415	arg1	"					1416:1416	glycan "wildcard"	1400:1416	glycan "wildcard"	1400:1416	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	1	95	theme	peptide	91:97	arg1	samples					119:125	peptide or digested protein samples	91:125	samples	119:125	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	3	96	theme	initial	878:884	arg1	database					893:900	the initial glycan database	874:900	the initial glycan database	874:900	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	2	97	theme	tandem	446:451	arg1	spectrometry					458:469	tandem mass spectrometry	446:469	tandem mass spectrometry	446:469	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	6	98	with	spectra	1554:1560	arg1	glycans					1581:1587	unanticipated glycans	1567:1587	unanticipated glycans	1567:1587	Also, new is glycan "wildcard" search, which allows an unspecified mass within a user-set mass range to be applied to N- or O-linked glycans and enables assignment of spectra with unanticipated glycans.
33578083	2	99	theme	identification	427:440	arg1	that					521:524	that	521:524	that	521:524	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	99	theme	identification	427:440	arg1	level					418:422	a reasonable level	405:422	a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools,	405:516	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	100	dep	sequence	537:544	arg1	meaning					570:576	meaning	570:576	meaning	570:576	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	2	101	theme	several	481:487	arg1	tools					511:515	several glycopeptide software tools	481:515	several glycopeptide software tools	481:515	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33578083	5	102	theme	204.087	1252:1258	arg1	three					1243:1247	three	1243:1247	three	1243:1247	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	102	theme	204.087	1252:1258	arg1	366.139					1313:1319	366.139	1313:1319	366.139	1313:1319	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	102	theme	204.087	1252:1258	arg1	274.092					1272:1278	274.092	1272:1278	274.092	1272:1278	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	102	theme	204.087	1252:1258	arg1	all					1337:1339	all	1337:1339	all	1337:1339	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	102	theme	204.087	1252:1258	arg1	204.087					1252:1258	204.087	1252:1258	204.087	1252:1258	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	0	103	theme	Wildcard	37:44	arg1	Search					46:51	Wildcard Search	37:51	Wildcard Search for Glycoproteomics	37:71	Peak Filtering, Peak Annotation, and Wildcard Search for Glycoproteomics.
33578083	5	104	dep	two	1232:1234	arg1	e.g.					1217:1220	e.g.	1217:1220	e.g.	1217:1220	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	105	theme	set	1350:1352	arg1	tolerance					1359:1367	a set mass tolerance	1348:1367	a set mass tolerance	1348:1367	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	3	106	with	peaks	949:953	arg1	glycans					858:864	unanticipated glycans	844:864	unanticipated glycans	844:864	Even at this level, however, glycopeptide analysis poses challenges: finding glycopeptide spectra when they are a tiny fraction of the total spectra; assigning spectra with unanticipated glycans, not in the initial glycan database; and finding, scoring, and labeling diagnostic peaks in tandem mass spectra.
33578083	5	107	dep	0.01 Da	1378:1384	arg1	e.g.					1370:1373	e.g.	1370:1373	e.g.	1370:1373	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	5	107	dep	0.01 Da	1378:1384	arg1	out					1236:1238	out	1236:1238	out	1236:1238	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	7	108	theme	Byonic	1619:1624	arg1	release					1608:1614	the next release	1599:1614	the next release of Byonic	1599:1624	Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications.
33578083	1	109	from	Glycopeptides	74:86	arg1	samples					119:125	peptide or digested protein samples	91:125	samples	119:125	Glycopeptides in peptide or digested protein samples pose a number of analytical and bioinformatics challenges beyond those posed by unmodified peptides or peptides with smaller posttranslational modifications.
33578083	7	110	theme	next	1603:1606	arg1	release					1608:1614	the next release	1599:1614	the next release of Byonic	1599:1624	Finally, the next release of Byonic supports user-specified peak annotations from user-defined posttranslational modifications.
33578083	5	111	theme	three	1243:1247	arg1	0.01 Da					1378:1384	± 0.01 Da	1376:1384	± 0.01 Da	1376:1384	Byonic now supports filtering spectra by m/z peaks, so that the user can limit attention to spectra with diagnostic peaks, e.g., at least two out of three of 204.087 for HexNAc, 274.092 for NeuAc (with water loss), and 366.139 for HexNAc-Hex, all within a set mass tolerance, e.g., ± 0.01 Da.
33578083	2	112	theme	spectrometry	377:388	arg1	experiment					390:399	a single mass spectrometry experiment	363:399	a single mass spectrometry experiment	363:399	Exact structural elucidation of glycans is generally beyond the capability of a single mass spectrometry experiment, so a reasonable level of identification for tandem mass spectrometry, taken by several glycopeptide software tools, is that of peptide sequence and glycan composition, meaning the number of monosaccharides of each distinct mass, e.g., HexNAc(2)Hex(5) rather than man5.
33186014	7	0	theme	lipid	1219:1223	arg1	pathway					1242:1248	a lipid carrier-mediated pathway	1217:1248	a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis	1217:1299	Our findings provide the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis.
33186014	5	1	from	ease	757:760	arg1	absence					800:806	the absence	796:806	the absence of detailed structural information	796:841	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	3	2	theme	enzymes	534:540	arg1	inhibition					496:505	inhibition	496:505	inhibition	496:505	However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging.
33186014	3	2	theme	enzymes	534:540	arg1	study					486:490	systematic study	475:490	systematic study	475:490	However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging.
33186014	4	3	theme	glycan	637:642	arg1	analysis					644:651	traditional glycan analysis	625:651	traditional glycan analysis	625:651	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	5	4	theme	information	831:841	arg1	absence					800:806	the absence	796:806	the absence of detailed structural information	796:841	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	7	5	theme	carrier-mediated	1225:1240	arg1	pathway					1242:1248	a lipid carrier-mediated pathway	1217:1248	a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis	1217:1299	Our findings provide the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis.
33186014	1	6	from	role	167:170	arg1	colonization					175:186	colonization	175:186	colonization of the host	175:198	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	7	7	theme	first	1152:1156	arg1	evidence					1158:1165	the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis	1148:1299	the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis	1148:1299	Our findings provide the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis.
33186014	2	8	theme	higher	344:349	arg1	glycans					357:363	higher order glycans	344:363	higher order glycans	344:363	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	5	9	theme	glycans	785:791	arg1	study					766:770	the study	762:770	the study of bacterial glycans	762:791	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	8	10	theme	glycosylation	1310:1322	arg1	mutants					1324:1330	Protein glycosylation mutants	1302:1330	Protein glycosylation mutants	1302:1330	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	9	11	theme	functional	1568:1577	arg1	importance					1579:1588	functional importance	1568:1588	functional importance	1568:1588	Broadly, our results suggest a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information.
33186014	6	12	theme	genes	1059:1063	arg1	identification					1041:1054	the identification	1037:1054	the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis	1037:1124	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	6	13	theme	mutant	955:960	arg1	strains					962:968	wild-type versus mutant strains	938:968	wild-type versus mutant strains of the gastric pathogen Helicobacter pylori	938:1012	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	4	14	contain	containing	588:597	arg1	glycans					580:586	glycans	580:586	glycans containing rare sugars refractory to traditional glycan analysis	580:651	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	4	14	contain	containing	588:597	arg2	sugars					604:609	rare sugars	599:609	rare sugars refractory to traditional glycan analysis	599:651	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	2	15	theme	distinctive	284:294	arg1	monosaccharides					296:310	distinctive monosaccharides	284:310	distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis	284:459	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	8	16	theme	Protein	1302:1308	arg1	mutants					1324:1330	Protein glycosylation mutants	1302:1330	Protein glycosylation mutants	1302:1330	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	3	17	theme	bacterial	510:518	arg1	enzymes					534:540	bacterial glycosylation enzymes	510:540	bacterial glycosylation enzymes	510:540	However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging.
33186014	4	18	theme	bacterial	680:688	arg1	glycans					690:696	bacterial glycans	680:696	bacterial glycans	680:696	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	1	19	theme	Bacterial	82:90	arg1	glycans					105:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	1	19	theme	Bacterial	82:90	arg1	targets					137:143	quintessential drug targets	117:143	quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion	117:237	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	8	20	theme	molecule	1397:1404	arg1	inhibitors					1420:1429	small molecule glycosylation inhibitors	1391:1429	small molecule glycosylation inhibitors	1391:1429	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	5	21	theme	metabolic	852:860	arg1	labeling					869:876	metabolic glycan labeling	852:876	metabolic glycan labeling	852:876	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	6	22	theme	wild-type	938:946	arg1	strains					962:968	wild-type versus mutant strains	938:968	wild-type versus mutant strains of the gastric pathogen Helicobacter pylori	938:1012	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	5	23	theme	glycan	862:867	arg1	labeling					869:876	metabolic glycan labeling	852:876	metabolic glycan labeling	852:876	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	1	24	theme	cell	92:95	arg1	glycans					105:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	1	24	theme	cell	92:95	arg1	targets					137:143	quintessential drug targets	117:143	quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion	117:237	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	0	25	theme	Glycan	10:15	arg1	Screen					32:37	Metabolic Glycan Labeling-Based Screen	0:37	Metabolic Glycan Labeling-Based Screen	0:37	Metabolic Glycan Labeling-Based Screen to Identify Bacterial Glycosylation Genes.
33186014	4	26	theme	refractory	611:620	arg1	sugars					604:609	rare sugars	599:609	rare sugars refractory to traditional glycan analysis	599:651	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	7	27	theme	H. pylori	1172:1180	arg1	glycosylation					1190:1202	H. pylori protein glycosylation	1172:1202	H. pylori protein glycosylation	1172:1202	Our findings provide the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis.
33186014	1	28	theme	surface	97:103	arg1	glycans					105:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	1	28	theme	surface	97:103	arg1	targets					137:143	quintessential drug targets	117:143	quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion	117:237	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	9	29	theme	facile	1463:1468	arg1	approach					1470:1477	a facile approach	1461:1477	a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information	1461:1642	Broadly, our results suggest a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information.
33186014	4	30	theme	biosynthesis	730:741	arg1	machinery					743:751	their biosynthesis machinery	724:751	their biosynthesis machinery	724:751	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	0	31	theme	Metabolic	0:8	arg1	Screen					32:37	Metabolic Glycan Labeling-Based Screen	0:37	Metabolic Glycan Labeling-Based Screen	0:37	Metabolic Glycan Labeling-Based Screen to Identify Bacterial Glycosylation Genes.
33186014	7	32	theme	protein	1182:1188	arg1	glycosylation					1190:1202	H. pylori protein glycosylation	1172:1202	H. pylori protein glycosylation	1172:1202	Our findings provide the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis.
33186014	8	33	theme	glycosylation	1406:1418	arg1	inhibitors					1420:1429	small molecule glycosylation inhibitors	1391:1429	small molecule glycosylation inhibitors	1391:1429	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	1	34	theme	host	195:198	arg1	colonization					175:186	colonization	175:186	colonization of the host	175:198	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	7	35	theme	lipopolysaccharide	1269:1286	arg1	biosynthesis					1288:1299	lipopolysaccharide biosynthesis	1269:1299	lipopolysaccharide biosynthesis	1269:1299	Our findings provide the first evidence that H. pylori protein glycosylation proceeds via a lipid carrier-mediated pathway that overlaps with lipopolysaccharide biosynthesis.
33186014	2	36	contain	contains	275:282	arg1	glycocalyx					264:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	2	36	contain	contains	275:282	arg2	monosaccharides					296:310	distinctive monosaccharides	284:310	distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis	284:459	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	9	37	theme	structural	1621:1630	arg1	information					1632:1642	glycan structural information	1614:1642	glycan structural information	1614:1642	Broadly, our results suggest a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information.
33186014	4	38	theme	glycans	690:696	arg1	study					671:675	the study	667:675	the study of bacterial glycans	667:696	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	4	38	theme	glycans	690:696	arg1	identification					706:719	the identification	702:719	the identification of their biosynthesis machinery	702:751	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	0	39	theme	Labeling-Based	17:30	arg1	Screen					32:37	Metabolic Glycan Labeling-Based Screen	0:37	Metabolic Glycan Labeling-Based Screen	0:37	Metabolic Glycan Labeling-Based Screen to Identify Bacterial Glycosylation Genes.
33186014	9	40	theme	bacterial	1493:1501	arg1	genes					1517:1521	bacterial glycosylation genes	1493:1521	bacterial glycosylation genes	1493:1521	Broadly, our results suggest a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information.
33186014	5	41	used	used	847:850	arg2	we					844:845	we	844:845	we	844:845	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	1	42	theme	quintessential	117:130	arg1	glycans					105:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	1	42	theme	quintessential	117:130	arg1	targets					137:143	quintessential drug targets	117:143	quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion	117:237	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	1	43	theme	pathogen	201:208	arg1	survival					210:217	pathogen survival	201:217	pathogen survival	201:217	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	8	44	theme	consistent	1358:1367	arg1	defects					1350:1356	fitness defects	1342:1356	fitness defects consistent with those induced by small molecule glycosylation inhibitors	1342:1429	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	3	45	theme	glycosylation	520:532	arg1	enzymes					534:540	bacterial glycosylation enzymes	510:540	bacterial glycosylation enzymes	510:540	However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging.
33186014	5	46	theme	glycan	899:904	arg1	biosynthesis					906:917	glycan biosynthesis	899:917	glycan biosynthesis	899:917	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	5	47	theme	bacterial	775:783	arg1	glycans					785:791	bacterial glycans	775:791	bacterial glycans	775:791	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	8	48	theme	small	1391:1395	arg1	inhibitors					1420:1429	small molecule glycosylation inhibitors	1391:1429	small molecule glycosylation inhibitors	1391:1429	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	2	49	theme	strain	429:434	arg1	fitness					436:442	strain fitness	429:442	strain fitness	429:442	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	3	50	dep	study	486:490	arg1	the					471:473	the	471:473	the	471:473	However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging.
33186014	4	51	theme	traditional	625:635	arg1	analysis					644:651	traditional glycan analysis	625:651	traditional glycan analysis	625:651	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	8	52	theme	fitness	1342:1348	arg1	defects					1350:1356	fitness defects	1342:1356	fitness defects consistent with those induced by small molecule glycosylation inhibitors	1342:1429	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	1	53	from	survival	210:217	arg1	colonization					175:186	colonization	175:186	colonization of the host	175:198	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	3	54	theme	systematic	475:484	arg1	study					486:490	systematic study	475:490	systematic study	475:490	However, the systematic study and inhibition of bacterial glycosylation enzymes remains challenging.
33186014	0	55	theme	Glycosylation	61:73	arg1	Genes					75:79	Bacterial Glycosylation Genes	51:79	Bacterial Glycosylation Genes	51:79	Metabolic Glycan Labeling-Based Screen to Identify Bacterial Glycosylation Genes.
33186014	6	56	theme	pylori	1007:1012	arg1	strains					962:968	wild-type versus mutant strains	938:968	wild-type versus mutant strains of the gastric pathogen Helicobacter pylori	938:1012	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	1	57	from	evasion	231:237	arg1	colonization					175:186	colonization	175:186	colonization of the host	175:198	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	4	58	theme	rare	599:602	arg1	sugars					604:609	rare sugars	599:609	rare sugars refractory to traditional glycan analysis	599:651	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	9	59	theme	information	1632:1642	arg1	absence					1603:1609	the absence	1599:1609	the absence of glycan structural information	1599:1642	Broadly, our results suggest a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information.
33186014	1	60	theme	drug	132:135	arg1	glycans					105:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	1	60	theme	drug	132:135	arg1	targets					137:143	quintessential drug targets	117:143	quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion	117:237	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	0	61	theme	Bacterial	51:59	arg1	Genes					75:79	Bacterial Glycosylation Genes	51:79	Bacterial Glycosylation Genes	51:79	Metabolic Glycan Labeling-Based Screen to Identify Bacterial Glycosylation Genes.
33186014	6	62	theme	Helicobacter	994:1005	arg1	pylori					1007:1012	the gastric pathogen Helicobacter pylori	973:1012	the gastric pathogen Helicobacter pylori	973:1012	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	5	63	from	changes	888:894	arg1	biosynthesis					906:917	glycan biosynthesis	899:917	glycan biosynthesis	899:917	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	2	64	theme	order	351:355	arg1	glycans					357:363	higher order glycans	344:363	higher order glycans	344:363	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	5	65	dep	detailed	811:818	arg1	structural					820:829	structural	820:829	structural	820:829	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	6	66	theme	pathogen	985:992	arg1	pylori					1007:1012	the gastric pathogen Helicobacter pylori	973:1012	the gastric pathogen Helicobacter pylori	973:1012	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	2	67	theme	envelope	255:262	arg1	glycocalyx					264:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	6	68	theme	lipopolysaccharide	1094:1111	arg1	biosynthesis					1113:1124	lipopolysaccharide biosynthesis	1094:1124	lipopolysaccharide biosynthesis	1094:1124	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	1	69	theme	due	145:147	arg1	glycans					105:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans	82:111	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	1	69	theme	due	145:147	arg1	targets					137:143	quintessential drug targets	117:143	quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion	117:237	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	8	70	with	consistent	1358:1367	arg1	those					1374:1378	those	1374:1378	those	1374:1378	Protein glycosylation mutants displayed fitness defects consistent with those induced by small molecule glycosylation inhibitors.
33186014	2	71	theme	cell	250:253	arg1	glycocalyx					264:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	4	72	theme	machinery	743:751	arg1	study					671:675	the study	667:675	the study of bacterial glycans	667:696	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	4	72	theme	machinery	743:751	arg1	identification					706:719	the identification	702:719	the identification of their biosynthesis machinery	702:751	Bacteria produce glycans containing rare sugars refractory to traditional glycan analysis, complicating the study of bacterial glycans and the identification of their biosynthesis machinery.
33186014	1	73	theme	immune	224:229	arg1	evasion					231:237	immune evasion	224:237	immune evasion	224:237	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33186014	2	74	theme	dense	244:248	arg1	glycocalyx					264:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx	240:273	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	9	75	theme	glycan	1614:1619	arg1	information					1632:1642	glycan structural information	1614:1642	glycan structural information	1614:1642	Broadly, our results suggest a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information.
33186014	2	76	theme	bacterial	386:394	arg1	structures					396:405	bacterial structures	386:405	bacterial structures that are critical for strain fitness and pathogenesis	386:459	The dense cell envelope glycocalyx contains distinctive monosaccharides that are stitched together into higher order glycans to yield exclusively bacterial structures that are critical for strain fitness and pathogenesis.
33186014	9	77	theme	glycosylation	1503:1515	arg1	genes					1517:1521	bacterial glycosylation genes	1493:1521	bacterial glycosylation genes	1493:1521	Broadly, our results suggest a facile approach to screen for bacterial glycosylation genes and gain insight into their biosynthesis and functional importance, even in the absence of glycan structural information.
33186014	5	78	theme	detailed	811:818	arg1	information					831:841	detailed structural information	811:841	detailed structural information	811:841	To ease the study of bacterial glycans in the absence of detailed structural information, we used metabolic glycan labeling to detect changes in glycan biosynthesis.
33186014	6	79	theme	gastric	977:983	arg1	pylori					1007:1012	the gastric pathogen Helicobacter pylori	973:1012	the gastric pathogen Helicobacter pylori	973:1012	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	6	80	gly	glycoprotein	1077:1088	arg1	glycoprotein					1077:1088	glycoprotein	1077:1088	glycoprotein	1077:1088	Here, we screened wild-type versus mutant strains of the gastric pathogen Helicobacter pylori, ultimately permitting the identification of genes involved in glycoprotein and lipopolysaccharide biosynthesis.
33186014	1	81	theme	critical	158:165	arg1	role					167:170	their critical role	152:170	their critical role in colonization of the host	152:198	Bacterial cell surface glycans are quintessential drug targets due to their critical role in colonization of the host, pathogen survival, and immune evasion.
33374805	5	0	theme	glycosylation	755:767	arg1	compounds					712:720	Four compounds	707:720	Four compounds	707:720	Four compounds were screened as potential CD147 glycosylation inhibitors.
33374805	5	0	theme	glycosylation	755:767	arg1	inhibitors					769:778	potential CD147 glycosylation inhibitors	739:778	potential CD147 glycosylation inhibitors	739:778	Four compounds were screened as potential CD147 glycosylation inhibitors.
33374805	7	1	theme	Hela	971:974	arg1	line					981:984	the Hela cell line	967:984	the Hela cell line	967:984	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	2	2	theme	tumors	454:459	arg1	prognosis					431:439	the poor prognosis	422:439	the poor prognosis of malignant tumors	422:459	Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors.
33374805	7	3	theme	cells	958:962	arg1	metastasis					937:946	the metastasis	933:946	the metastasis of cancer cells	933:962	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	7	3	theme	cells	958:962	arg1	production					910:919	the production	906:919	the production of MMPs	906:927	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	1	4	theme	matrix	238:243	arg1	MMPs					265:268	MMPs	265:268	MMPs	265:268	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	4	theme	matrix	238:243	arg1	metalloproteinases					245:262	matrix metalloproteinases	238:262	matrix metalloproteinases (MMPs)	238:269	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	9	5	theme	potential	1164:1172	arg1	inhibitors					1196:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.
33374805	3	6	theme	little	495:500	arg1	development					502:512	little development	495:512	little development of target-specific inhibitors for CD147 glycosylation	495:566	However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation.
33374805	1	7	theme	metalloproteinases	245:262	arg1	secretion					225:233	secretion	225:233	secretion of matrix metalloproteinases (MMPs)	225:269	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	7	theme	metalloproteinases	245:262	arg1	promotion					276:284	promotion	276:284	promotion of tumor metastasis	276:304	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	7	theme	metalloproteinases	245:262	arg1	maturation					204:213	the maturation	200:213	the maturation of CD147	200:222	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	9	8	theme	CD147	1174:1178	arg1	inhibitors					1196:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.
33374805	7	9	theme	Further	849:855	arg1	experiments					857:867	Further experiments	849:867	Further experiments	849:867	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	7	10	theme	cancer	951:956	arg1	cells					958:962	cancer cells	951:962	cancer cells	951:962	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	4	11	theme	CD147	620:624	arg1	inhibitors					640:649	CD147 glycosylation inhibitors	620:649	CD147 glycosylation inhibitors	620:649	In this work, we report a strategy for discovering CD147 glycosylation inhibitors through computer-aided screening and inhibition assays.
33374805	2	12	theme	poor	426:429	arg1	prognosis					431:439	the poor prognosis	422:439	the poor prognosis of malignant tumors	422:459	Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors.
33374805	0	13	theme	CD147	39:43	arg1	Inhibitors					54:63	CD147 N-Glycan Inhibitors	39:63	CD147 N-Glycan Inhibitors	39:63	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	9	14	theme	inhibitors	1196:1205	arg1	structures					1140:1149	the structures	1136:1149	the structures of the other potential CD147 N-glycosylation inhibitors	1136:1205	Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.
33374805	0	15	theme	New	68:70	arg1	Direction					72:80	A New Direction	66:80	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.	0:118	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	3	16	theme	inhibitors	533:542	arg1	development					502:512	little development	495:512	little development of target-specific inhibitors for CD147 glycosylation	495:566	However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation.
33374805	1	17	theme	CD147	173:177	arg1	functions					179:187	CD147 functions	173:187	CD147 functions	173:187	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	17	theme	CD147	173:177	arg1	promotion					276:284	promotion	276:284	promotion of tumor metastasis	276:304	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	17	theme	CD147	173:177	arg1	secretion					225:233	secretion	225:233	secretion of matrix metalloproteinases (MMPs)	225:269	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	17	theme	CD147	173:177	arg1	maturation					204:213	the maturation	200:213	the maturation of CD147	200:222	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	7	18	theme	MMPs	924:927	arg1	metastasis					937:946	the metastasis	933:946	the metastasis of cancer cells	933:962	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	7	18	theme	MMPs	924:927	arg1	production					910:919	the production	906:919	the production of MMPs	906:927	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	2	19	theme	cancer	357:362	arg1	types					364:368	various cancer types	349:368	various cancer types	349:368	Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors.
33374805	0	20	theme	Metastasis	108:117	arg1	Treatment					89:97	the Treatment	85:97	the Treatment of Tumor Metastasis	85:117	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	9	21	theme	N-glycosylation	1180:1194	arg1	inhibitors					1196:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.
33374805	9	22	theme	other	1158:1162	arg1	inhibitors					1196:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	the other potential CD147 N-glycosylation inhibitors	1154:1205	Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.
33374805	0	23	theme	Biological	14:23	arg1	Evaluation					25:34	Biological Evaluation	14:34	Biological Evaluation	14:34	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	0	24	theme	Tumor	102:106	arg1	Metastasis					108:117	Tumor Metastasis	102:117	Tumor Metastasis	102:117	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	0	25	from	Direction	72:80	arg1	Treatment					89:97	the Treatment	85:97	the Treatment of Tumor Metastasis	85:117	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	3	26	theme	target-specific	517:531	arg1	inhibitors					533:542	target-specific inhibitors	517:542	target-specific inhibitors for CD147 glycosylation	517:566	However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation.
33374805	4	27	theme	computer-aided	659:672	arg1	screening					674:682	computer-aided screening	659:682	computer-aided screening	659:682	In this work, we report a strategy for discovering CD147 glycosylation inhibitors through computer-aided screening and inhibition assays.
33374805	2	28	theme	malignant	444:452	arg1	tumors					454:459	malignant tumors	444:459	malignant tumors	444:459	Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors.
33374805	4	29	theme	inhibition	688:697	arg1	assays					699:704	inhibition assays	688:704	inhibition assays	688:704	In this work, we report a strategy for discovering CD147 glycosylation inhibitors through computer-aided screening and inhibition assays.
33374805	8	30	theme	E-cadherin	1060:1069	arg1	expression					1046:1055	the expression	1042:1055	the expression of E-cadherin	1042:1069	Results further suggest that compound 72 could promote the expression of E-cadherin by targeting CD147, thereby inhibiting tumor migration.
33374805	1	31	theme	functions	179:187	arg1	regulation					159:168	the regulation	155:168	the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis	155:304	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	9	32	theme	future	1243:1248	arg1	optimization					1250:1261	future optimization	1243:1261	future optimization	1243:1261	Finally, the structures of the other potential CD147 N-glycosylation inhibitors may eventually provide guidance for future optimization.
33374805	0	33	theme	Inhibitors	54:63	arg1	Discovery					0:8	Discovery	0:8	Discovery	0:8	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	0	33	theme	Inhibitors	54:63	arg1	Evaluation					25:34	Biological Evaluation	14:34	Biological Evaluation	14:34	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	3	34	theme	CD147	548:552	arg1	glycosylation					554:566	CD147 glycosylation	548:566	CD147 glycosylation	548:566	However, to date, there has been little development of target-specific inhibitors for CD147 glycosylation.
33374805	0	35	theme	N-Glycan	45:52	arg1	Inhibitors					54:63	CD147 N-Glycan Inhibitors	39:63	CD147 N-Glycan Inhibitors	39:63	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33374805	1	36	theme	tumor	289:293	arg1	metastasis					295:304	tumor metastasis	289:304	tumor metastasis	289:304	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	6	37	theme	best	833:836	arg1	compound					791:798	compound 72	791:801	compound 72	791:801	Of these, compound 72 was finally identified as the best candidate.
33374805	6	37	theme	best	833:836	arg1	candidate					838:846	the best candidate	829:846	the best candidate	829:846	Of these, compound 72 was finally identified as the best candidate.
33374805	4	38	theme	glycosylation	626:638	arg1	inhibitors					640:649	CD147 glycosylation inhibitors	620:649	CD147 glycosylation inhibitors	620:649	In this work, we report a strategy for discovering CD147 glycosylation inhibitors through computer-aided screening and inhibition assays.
33374805	1	39	theme	metastasis	295:304	arg1	secretion					225:233	secretion	225:233	secretion of matrix metalloproteinases (MMPs)	225:269	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	39	theme	metastasis	295:304	arg1	promotion					276:284	promotion	276:284	promotion of tumor metastasis	276:304	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	39	theme	metastasis	295:304	arg1	maturation					204:213	the maturation	200:213	the maturation of CD147	200:222	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	8	40	theme	tumor	1110:1114	arg1	migration					1116:1124	tumor migration	1110:1124	tumor migration	1110:1124	Results further suggest that compound 72 could promote the expression of E-cadherin by targeting CD147, thereby inhibiting tumor migration.
33374805	2	41	theme	Glycosylated	307:318	arg1	CD147					320:324	Glycosylated CD147	307:324	Glycosylated CD147	307:324	Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors.
33374805	7	42	theme	cell	976:979	arg1	line					981:984	the Hela cell line	967:984	the Hela cell line	967:984	Further experiments confirmed that compound 72 inhibited the production of MMPs and the metastasis of cancer cells in the Hela cell line.
33374805	1	43	theme	CD147	218:222	arg1	secretion					225:233	secretion	225:233	secretion of matrix metalloproteinases (MMPs)	225:269	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	43	theme	CD147	218:222	arg1	promotion					276:284	promotion	276:284	promotion of tumor metastasis	276:304	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	1	43	theme	CD147	218:222	arg1	maturation					204:213	the maturation	200:213	the maturation of CD147	200:222	N-glycosylation is instrumental to the regulation of CD147 functions, including the maturation of CD147, secretion of matrix metalloproteinases (MMPs), and promotion of tumor metastasis.
33374805	5	44	theme	potential	739:747	arg1	compounds					712:720	Four compounds	707:720	Four compounds	707:720	Four compounds were screened as potential CD147 glycosylation inhibitors.
33374805	5	44	theme	potential	739:747	arg1	inhibitors					769:778	potential CD147 glycosylation inhibitors	739:778	potential CD147 glycosylation inhibitors	739:778	Four compounds were screened as potential CD147 glycosylation inhibitors.
33374805	2	45	theme	various	349:355	arg1	types					364:368	various cancer types	349:368	various cancer types	349:368	Glycosylated CD147 is highly expressed in various cancer types, participates in metastasis, and is associated with the poor prognosis of malignant tumors.
33374805	5	46	theme	CD147	749:753	arg1	compounds					712:720	Four compounds	707:720	Four compounds	707:720	Four compounds were screened as potential CD147 glycosylation inhibitors.
33374805	5	46	theme	CD147	749:753	arg1	inhibitors					769:778	potential CD147 glycosylation inhibitors	739:778	potential CD147 glycosylation inhibitors	739:778	Four compounds were screened as potential CD147 glycosylation inhibitors.
33374805	0	47	dep	Discovery	0:8	arg1	Direction					72:80	A New Direction	66:80	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.	0:118	Discovery and Biological Evaluation of CD147 N-Glycan Inhibitors: A New Direction in the Treatment of Tumor Metastasis.
33600485	5	0	theme	structures	761:770	arg1	Characterization					722:737	Characterization	722:737	Characterization of the exact N-glycan structures attached on either PrPC or PrPSc	722:803	Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking.
33600485	11	1	theme	major	1354:1358	arg1	differences					1360:1370	no major differences	1351:1370	no major differences in glycan composition	1351:1392	The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.
33600485	4	2	gly	occupancy	657:665	arg2	sites					688:692	two glycosylation sites	670:692	two glycosylation sites	670:692	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	4	3	theme	prion	701:705	arg1	PrP					716:718	PrP	716:718	PrP	716:718	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	4	3	theme	prion	701:705	arg1	protein					707:713	the prion protein	697:713	the prion protein (PrP)	697:719	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	6	4	from	strains	912:918	arg1	N-glycans					871:879	N-glycans	871:879	N-glycans from two different sheep prion strains	871:918	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	6	4	from	strains	912:918	arg1	comparison					857:866	comparison	857:866	comparison	857:866	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	6	4	from	strains	912:918	arg1	characterization					836:851	characterization	836:851	characterization	836:851	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	6	5	theme	prion	906:910	arg1	strains					912:918	two different sheep prion strains	886:918	two different sheep prion strains	886:918	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	9	6	theme	glycosylation	1179:1191	arg1	sites					1193:1197	both glycosylation sites	1174:1197	both glycosylation sites	1174:1197	A total of 100 structures were detected on both glycosylation sites.
33600485	1	7	theme	mammalian	155:163	arg1	species					165:171	mammalian species	155:171	mammalian species	155:171	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	11	8	theme	prion	1482:1486	arg1	strains					1488:1494	the two analyzed prion strains	1465:1494	the two analyzed prion strains	1465:1494	The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.
33600485	8	9	theme	liquid	1026:1031	arg1	chromatography					1033:1046	liquid chromatography	1026:1046	liquid chromatography coupled to electrospray mass spectrometry	1026:1088	By using liquid chromatography coupled to electrospray mass spectrometry, a site-specific analysis was performed.
33600485	6	10	theme	sheep	900:904	arg1	strains					912:918	two different sheep prion strains	886:918	two different sheep prion strains	886:918	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	7	11	theme	brain	963:967	arg1	tissue					969:974	brain tissue	963:974	brain tissue	963:974	PrPSc from both strains was isolated from brain tissue and enzymatically digested with trypsin.
33600485	3	12	theme	distinct	489:496	arg1	states					513:518	distinct conformational states	489:518	distinct conformational states called strains	489:533	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	4	13	theme	three-band	596:605	arg1	pattern					618:624	a characteristic three-band immunoblot pattern	579:624	a characteristic three-band immunoblot pattern	579:624	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	6	14	theme	different	890:898	arg1	strains					912:918	two different sheep prion strains	886:918	two different sheep prion strains	886:918	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	4	15	gly	glycosylation	674:686	arg2	sites					688:692	two glycosylation sites	670:692	two glycosylation sites	670:692	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	4	15	gly	glycosylation	674:686	arg2	two					670:672	two	670:672	two	670:672	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	10	16	theme	additional	1284:1293	arg1	structures					1298:1307	additional 40 structures	1284:1307	additional 40 structures reported	1284:1316	The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported.
33600485	4	17	theme	characteristic	581:594	arg1	pattern					618:624	a characteristic three-band immunoblot pattern	579:624	a characteristic three-band immunoblot pattern	579:624	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	1	18	theme	neurodegenerative	102:118	arg1	humans					184:189	humans	184:189	humans	184:189	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	1	18	theme	neurodegenerative	102:118	arg1	diseases					120:127	neurodegenerative diseases	102:127	neurodegenerative diseases	102:127	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	8	19	theme	electrospray	1059:1070	arg1	spectrometry					1077:1088	electrospray mass spectrometry	1059:1088	electrospray mass spectrometry	1059:1088	By using liquid chromatography coupled to electrospray mass spectrometry, a site-specific analysis was performed.
33600485	1	20	theme	Prion	72:76	arg1	diseases					78:85	Prion diseases	72:85	Prion diseases	72:85	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	1	20	theme	Prion	72:76	arg1	group					93:97	a group	91:97	a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans	91:189	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	1	20	theme	Prion	72:76	arg1	diseases					120:127	neurodegenerative diseases	102:127	neurodegenerative diseases	102:127	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	4	21	theme	glycosylation	674:686	arg1	sites					688:692	two glycosylation sites	670:692	two glycosylation sites	670:692	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	1	22	theme	species	165:171	arg1	range					146:150	a wide range	139:150	a wide range of mammalian species	139:171	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	3	23	theme	diverse	379:385	arg1	spectrum					387:394	the diverse spectrum	375:394	the diverse spectrum of illnesses	375:407	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	2	24	theme	prion	256:260	arg1	PrPSc					271:275	PrPSc	271:275	PrPSc	271:275	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	2	24	theme	prion	256:260	arg1	protein					262:268	the abnormally folded scrapie prion protein	226:268	the abnormally folded scrapie prion protein (PrPSc)	226:276	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	6	25	theme	N-glycans	871:879	arg1	comparison					857:866	comparison	857:866	comparison	857:866	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	6	25	theme	N-glycans	871:879	arg1	characterization					836:851	characterization	836:851	characterization	836:851	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	10	26	from	one	1252:1254	arg1	PrP					1265:1267	mouse PrP	1259:1267	mouse PrP	1259:1267	The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported.
33600485	4	27	from	occupancy	657:665	arg1	PrP					716:718	PrP	716:718	PrP	716:718	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	4	27	from	occupancy	657:665	arg1	protein					707:713	the prion protein	697:713	the prion protein (PrP)	697:719	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	3	28	theme	illnesses	399:407	arg1	spectrum					387:394	the diverse spectrum	375:394	the diverse spectrum of illnesses	375:407	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	0	29	theme	Site-specific	0:12	arg1	analysis					14:21	Site-specific analysis	0:21	Site-specific analysis of N-glycans from different sheep prion strains.	0:70	Site-specific analysis of N-glycans from different sheep prion strains.
33600485	8	30	theme	mass	1072:1075	arg1	spectrometry					1077:1088	electrospray mass spectrometry	1059:1088	electrospray mass spectrometry	1059:1088	By using liquid chromatography coupled to electrospray mass spectrometry, a site-specific analysis was performed.
33600485	6	31	from	characterization	836:851	arg1	strains					912:918	two different sheep prion strains	886:918	two different sheep prion strains	886:918	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	0	32	theme	N-glycans	26:34	arg1	analysis					14:21	Site-specific analysis	0:21	Site-specific analysis of N-glycans from different sheep prion strains.	0:70	Site-specific analysis of N-glycans from different sheep prion strains.
33600485	9	33	gly	glycosylation	1179:1191	arg2	sites					1193:1197	both glycosylation sites	1174:1197	both glycosylation sites	1174:1197	A total of 100 structures were detected on both glycosylation sites.
33600485	3	34	theme	prion	358:362	arg1	disorders					364:372	prion disorders	358:372	prion disorders	358:372	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	10	35	theme	N-glycan	1204:1211	arg1	similar					1237:1243	similar	1237:1243	similar	1237:1243	The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported.
33600485	10	35	theme	N-glycan	1204:1211	arg1	profile					1213:1219	The N-glycan profile	1200:1219	The N-glycan profile	1200:1219	The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported.
33600485	4	36	from	differences	638:648	arg1	PrP					716:718	PrP	716:718	PrP	716:718	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	4	36	from	differences	638:648	arg1	protein					707:713	the prion protein	697:713	the prion protein (PrP)	697:719	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	4	36	from	differences	638:648	arg1	occupancy					657:665	the occupancy	653:665	the occupancy of two glycosylation sites on the prion protein (PrP)	653:719	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	3	37	theme	different	443:451	arg1	isoforms					453:460	different isoforms	443:460	different isoforms of PrPSc	443:469	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	0	38	theme	different	41:49	arg1	strains					63:69	different sheep prion strains	41:69	different sheep prion strains	41:69	Site-specific analysis of N-glycans from different sheep prion strains.
33600485	11	39	theme	glycan	1375:1380	arg1	composition					1382:1392	glycan composition	1375:1392	glycan composition	1375:1392	The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.
33600485	9	40	located	detected	1162:1169	arg2	total					1133:1137	A total	1131:1137	A total of 100 structures	1131:1155	A total of 100 structures were detected on both glycosylation sites.
33600485	9	40	located	detected	1162:1169	arg1	sites					1193:1197	both glycosylation sites	1174:1197	both glycosylation sites	1174:1197	A total of 100 structures were detected on both glycosylation sites.
33600485	8	41	theme	site-specific	1093:1105	arg1	analysis					1107:1114	a site-specific analysis	1091:1114	a site-specific analysis	1091:1114	By using liquid chromatography coupled to electrospray mass spectrometry, a site-specific analysis was performed.
33600485	2	42	theme	disease	217:223	arg1	course					203:208	the course	199:208	the course of the disease	199:223	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	0	43	theme	prion	57:61	arg1	strains					63:69	different sheep prion strains	41:69	different sheep prion strains	41:69	Site-specific analysis of N-glycans from different sheep prion strains.
33600485	6	44	dep	characterization	836:851	arg1	the					832:834	the	832:834	the	832:834	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	0	45	from	strains	63:69	arg1	analysis					14:21	Site-specific analysis	0:21	Site-specific analysis of N-glycans from different sheep prion strains.	0:70	Site-specific analysis of N-glycans from different sheep prion strains.
33600485	3	46	theme	PrPSc	465:469	arg1	isoforms					453:460	different isoforms	443:460	different isoforms of PrPSc	443:469	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	0	47	theme	sheep	51:55	arg1	strains					63:69	different sheep prion strains	41:69	different sheep prion strains	41:69	Site-specific analysis of N-glycans from different sheep prion strains.
33600485	11	48	from	differences	1450:1460	arg1	strains					1488:1494	the two analyzed prion strains	1465:1494	the two analyzed prion strains	1465:1494	The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.
33600485	5	49	attach	attached	772:779	arg3	PrPC					791:794	PrPC	791:794	PrPC	791:794	Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking.
33600485	5	49	attach	attached	772:779	arg2	structures					761:770	the exact N-glycan structures	742:770	the exact N-glycan structures attached on either PrPC or PrPSc	742:803	Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking.
33600485	5	49	attach	attached	772:779	arg3	PrPSc					799:803	PrPSc	799:803	PrPSc	799:803	Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking.
33600485	1	50	theme	diseases	120:127	arg1	diseases					78:85	Prion diseases	72:85	Prion diseases	72:85	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	1	50	theme	diseases	120:127	arg1	group					93:97	a group	91:97	a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans	91:189	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	1	50	theme	diseases	120:127	arg1	diseases					120:127	neurodegenerative diseases	102:127	neurodegenerative diseases	102:127	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	1	50	theme	diseases	120:127	arg1	humans					184:189	humans	184:189	humans	184:189	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	7	51	from	strains	937:943	arg1	PrPSc					921:925	PrPSc	921:925	PrPSc from both strains	921:943	PrPSc from both strains was isolated from brain tissue and enzymatically digested with trypsin.
33600485	11	52	from	differences	1360:1370	arg1	composition					1382:1392	glycan composition	1375:1392	glycan composition	1375:1392	The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.
33600485	2	53	theme	scrapie	248:254	arg1	PrPSc					271:275	PrPSc	271:275	PrPSc	271:275	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	2	53	theme	scrapie	248:254	arg1	protein					262:268	the abnormally folded scrapie prion protein	226:268	the abnormally folded scrapie prion protein (PrPSc)	226:276	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	4	54	theme	sites	688:692	arg1	occupancy					657:665	the occupancy	653:665	the occupancy of two glycosylation sites on the prion protein (PrP)	653:719	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	2	55	theme	nervous	305:311	arg1	system					313:318	the central nervous system	293:318	the central nervous system where it causes neurodegeneration	293:352	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	11	56	theme	analyzed	1473:1480	arg1	strains					1488:1494	the two analyzed prion strains	1465:1494	the two analyzed prion strains	1465:1494	The results presented here show no major differences in glycan composition, suggesting that glycans may not be responsible for the differences in the two analyzed prion strains.
33600485	9	57	theme	structures	1146:1155	arg1	total					1133:1137	A total	1131:1137	A total of 100 structures	1131:1155	A total of 100 structures were detected on both glycosylation sites.
33600485	2	58	theme	folded	241:246	arg1	PrPSc					271:275	PrPSc	271:275	PrPSc	271:275	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	2	58	theme	folded	241:246	arg1	protein					262:268	the abnormally folded scrapie prion protein	226:268	the abnormally folded scrapie prion protein (PrPSc)	226:276	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	2	59	theme	central	297:303	arg1	system					313:318	the central nervous system	293:318	the central nervous system where it causes neurodegeneration	293:352	During the course of the disease, the abnormally folded scrapie prion protein (PrPSc) accumulates in the central nervous system where it causes neurodegeneration.
33600485	3	60	theme	isoforms	453:460	arg1	presence					431:438	the presence	427:438	the presence of different isoforms of PrPSc	427:469	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	5	61	theme	exact	746:750	arg1	structures					761:770	the exact N-glycan structures	742:770	the exact N-glycan structures attached on either PrPC or PrPSc	742:803	Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking.
33600485	7	62	attach	isolated	949:956	arg2	PrPSc					921:925	PrPSc	921:925	PrPSc from both strains	921:943	PrPSc from both strains was isolated from brain tissue and enzymatically digested with trypsin.
33600485	7	62	attach	isolated	949:956	arg1	tissue					969:974	brain tissue	963:974	brain tissue	963:974	PrPSc from both strains was isolated from brain tissue and enzymatically digested with trypsin.
33600485	1	63	theme	wide	141:144	arg1	range					146:150	a wide range	139:150	a wide range of mammalian species	139:171	Prion diseases are a group of neurodegenerative diseases affecting a wide range of mammalian species, including humans.
33600485	4	64	from	protein	707:713	arg1	differences					638:648	differences	638:648	differences in the occupancy of two glycosylation sites on the prion protein (PrP)	638:719	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	5	65	theme	N-glycan	752:759	arg1	structures					761:770	the exact N-glycan structures	742:770	the exact N-glycan structures attached on either PrPC or PrPSc	742:803	Characterization of the exact N-glycan structures attached on either PrPC or PrPSc is lacking.
33600485	6	66	from	comparison	857:866	arg1	strains					912:918	two different sheep prion strains	886:918	two different sheep prion strains	886:918	Here we report the characterization and comparison of N-glycans from two different sheep prion strains.
33600485	4	67	theme	immunoblot	607:616	arg1	pattern					618:624	a characteristic three-band immunoblot pattern	579:624	a characteristic three-band immunoblot pattern	579:624	Strains are biochemically distinguished by a characteristic three-band immunoblot pattern, defined by differences in the occupancy of two glycosylation sites on the prion protein (PrP).
33600485	3	68	theme	conformational	498:511	arg1	states					513:518	distinct conformational states	489:518	distinct conformational states called strains	489:533	In prion disorders, the diverse spectrum of illnesses exists because of the presence of different isoforms of PrPSc where they occupy distinct conformational states called strains.
33600485	10	69	theme	mouse	1259:1263	arg1	PrP					1265:1267	mouse PrP	1259:1267	mouse PrP	1259:1267	The N-glycan profile was shown to be similar to the one on mouse PrP, however, with additional 40 structures reported.
32364434	7	0	from	tube	1444:1447	arg1	microscale					1395:1404	microscale	1395:1404	microscale	1395:1404	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	9	1	theme	sialic	1804:1809	arg1	linkages					1816:1823	sialic acid linkages	1804:1823	sialic acid linkages	1804:1823	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	6	2	from	sources	1143:1149	arg1	glycans					1122:1128	glycans	1122:1128	glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1122:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	2	from	sources	1143:1149	arg1	analysis					1110:1117	micropermethylation-based high-throughput structural analysis	1057:1117	micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1057:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	3	3	theme	quantitative	559:570	arg1	characterization					572:587	characterization	572:587	characterization	572:587	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	5	4	theme	large	933:937	arg1	sets					946:949	large sample sets	933:949	large sample sets	933:949	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	9	5	theme	linkages	1816:1823	arg1	examples					1792:1799	the examples	1788:1799	the examples of sialic acid linkages	1788:1823	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	9	5	theme	linkages	1816:1823	arg1	N-acetylglucosamine					1847:1865	bisecting GlcNAc (N-acetylglucosamine)	1829:1866	bisecting GlcNAc (N-acetylglucosamine) on the glycans	1829:1881	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	6	6	theme	ionization-mass	1262:1276	arg1	ESI-MSn					1292:1298	ESI-MSn	1292:1298	ESI-MSn	1292:1298	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	6	theme	ionization-mass	1262:1276	arg1	spectrometry					1278:1289	an automated tandem electrospray ionization-mass spectrometry	1229:1289	an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform	1229:1308	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	4	7	theme	glycans	738:744	arg1	characterization					709:724	the structural characterization	694:724	the structural characterization of released glycans by mass spectrometry (MS)	694:770	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	10	8	theme	high-throughput	1915:1929	arg1	screening					1931:1939	the high-throughput screening	1911:1939	the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics	1911:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	5	9	theme	sets	946:949	arg1	processing					919:928	the processing	915:928	the processing of large sample sets in nanogram amounts	915:969	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	6	10	theme	wide	1039:1042	arg1	potential					1044:1052	the wide potential	1035:1052	the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1035:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	9	11	theme	bisecting	1829:1837	arg1	N-acetylglucosamine					1847:1865	bisecting GlcNAc (N-acetylglucosamine)	1829:1866	bisecting GlcNAc (N-acetylglucosamine) on the glycans	1829:1881	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	6	12	theme	tandem	1242:1247	arg1	ESI-MSn					1292:1298	ESI-MSn	1292:1298	ESI-MSn	1292:1298	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	12	theme	tandem	1242:1247	arg1	spectrometry					1278:1289	an automated tandem electrospray ionization-mass spectrometry	1229:1289	an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform	1229:1308	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	2	13	theme	serum	321:325	arg1	half-life					327:335	serum half-life	321:335	serum half-life	321:335	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	1	14	theme	cellular	139:146	arg1	functions					148:156	various molecular and cellular functions	117:156	various molecular and cellular functions	117:156	Glycoproteins play key roles in various molecular and cellular functions and are among the most difficult to analyze biomolecules on account of their microheterogeneity, non-template-driven synthesis, and low abundances.
32364434	4	15	theme	structural	698:707	arg1	characterization					709:724	the structural characterization	694:724	the structural characterization of released glycans by mass spectrometry (MS)	694:770	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	7	16	theme	C18	1467:1469	arg1	cleanup					1481:1487	a C18 tip-based cleanup	1465:1487	a C18 tip-based cleanup through a shorter and simple process	1465:1524	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	5	17	theme	sample	995:1000	arg1	handling					1002:1009	high-throughput sample handling	979:1009	high-throughput sample handling	979:1009	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	6	18	theme	glycans	1122:1128	arg1	analysis					1110:1117	micropermethylation-based high-throughput structural analysis	1057:1117	micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1057:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	8	19	theme	in-depth	1573:1580	arg1	characterization					1603:1618	in-depth automated structural characterization	1573:1618	an in-depth automated structural characterization MS program for permethylated N/O-glycans	1570:1659	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	4	20	theme	mass	749:752	arg1	spectrometry					754:765	mass spectrometry	749:765	mass spectrometry (MS)	749:770	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	4	20	theme	mass	749:752	arg1	MS					768:769	MS	768:769	MS	768:769	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	10	21	theme	sample	1967:1972	arg1	sets					1974:1977	large sample sets	1961:1977	large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics	1961:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	21	theme	sample	1967:1972	arg1	therapeutics					2051:2062	glycoprotein therapeutics	2038:2062	glycoprotein therapeutics	2038:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	21	theme	sample	1967:1972	arg1	biomarkers					2023:2032	clinical glycan biomarkers	2007:2032	clinical glycan biomarkers	2007:2032	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	21	theme	sample	1967:1972	arg1	glycoproteins					1982:1994	glycoproteins	1982:1994	glycoproteins	1982:1994	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	5	22	theme	nanogram	954:961	arg1	amounts					963:969	nanogram amounts	954:969	nanogram amounts	954:969	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	6	23	theme	analysis	1110:1117	arg1	potential					1044:1052	the wide potential	1035:1052	the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1035:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	8	24	theme	structural	1592:1601	arg1	characterization					1603:1618	in-depth automated structural characterization	1573:1618	an in-depth automated structural characterization MS program for permethylated N/O-glycans	1570:1659	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	7	25	attach	released	1323:1330	arg2	permethylated					1378:1390	permethylated	1378:1390	permethylated	1378:1390	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	7	25	attach	released	1323:1330	arg2	glycans					1315:1321	The glycans	1311:1321	The glycans released from the plasma, cells, and glycoproteins	1311:1372	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	7	25	attach	released	1323:1330	arg1	cells					1349:1353	cells	1349:1353	cells	1349:1353	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	7	25	attach	released	1323:1330	arg1	glycoproteins					1360:1372	glycoproteins	1360:1372	glycoproteins	1360:1372	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	7	25	attach	released	1323:1330	arg1	plasma					1341:1346	the plasma	1337:1346	the plasma	1337:1346	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	10	26	from	screening	1931:1939	arg1	sets					1974:1977	large sample sets	1961:1977	large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics	1961:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	26	from	screening	1931:1939	arg1	therapeutics					2051:2062	glycoprotein therapeutics	2038:2062	glycoprotein therapeutics	2038:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	26	from	screening	1931:1939	arg1	biomarkers					2023:2032	clinical glycan biomarkers	2007:2032	clinical glycan biomarkers	2007:2032	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	26	from	screening	1931:1939	arg1	glycoproteins					1982:1994	glycoproteins	1982:1994	glycoproteins	1982:1994	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	6	27	theme	high-throughput	1083:1097	arg1	analysis					1110:1117	micropermethylation-based high-throughput structural analysis	1057:1117	micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1057:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	8	28	theme	MS	1620:1621	arg1	program					1623:1629	an in-depth automated structural characterization MS program	1570:1629	an in-depth automated structural characterization MS program for permethylated N/O-glycans	1570:1659	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	1	29	theme	key	104:106	arg1	roles					108:112	key roles	104:112	key roles	104:112	Glycoproteins play key roles in various molecular and cellular functions and are among the most difficult to analyze biomolecules on account of their microheterogeneity, non-template-driven synthesis, and low abundances.
32364434	6	30	gly	glycoproteins	1206:1218	arg1	glycoproteins					1206:1218	purified glycoproteins	1197:1218	purified glycoproteins	1197:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	31	theme	human	1162:1166	arg1	plasma					1168:1173	human plasma	1162:1173	human plasma	1162:1173	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	2	32	theme	glycoproteins	393:405	arg1	stability					310:318	stability	310:318	stability	310:318	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	32	theme	glycoproteins	393:405	arg1	half-life					327:335	serum half-life	321:335	serum half-life	321:335	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	32	theme	glycoproteins	393:405	arg1	activity					369:376	biological activity	358:376	biological activity	358:376	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	32	theme	glycoproteins	393:405	arg1	immunogenicity					338:351	immunogenicity	338:351	immunogenicity	338:351	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	33	gly	glycoproteins	393:405	arg1	biomarkers					444:453	biomarkers	444:453	biomarkers	444:453	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	33	gly	glycoproteins	393:405	arg1	vaccines					430:437	vaccines	430:437	vaccines	430:437	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	33	gly	glycoproteins	393:405	arg1	glycoproteins					393:405	therapeutic glycoproteins	381:405	therapeutic glycoproteins	381:405	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	33	gly	glycoproteins	393:405	arg1	antibodies					418:427	antibodies	418:427	antibodies	418:427	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	5	34	theme	glycans	895:901	arg1	permethylation					877:890	facile permethylation	870:890	facile permethylation of glycans	870:901	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	1	35	theme	molecular	125:133	arg1	functions					148:156	various molecular and cellular functions	117:156	various molecular and cellular functions	117:156	Glycoproteins play key roles in various molecular and cellular functions and are among the most difficult to analyze biomolecules on account of their microheterogeneity, non-template-driven synthesis, and low abundances.
32364434	7	36	theme	96-well	1411:1417	arg1	plate					1419:1423	a 96-well plate	1409:1423	a 96-well plate	1409:1423	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	8	37	theme	high-throughput	1682:1696	arg1	acquisition					1719:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	10	38	theme	clinical	2007:2014	arg1	biomarkers					2023:2032	clinical glycan biomarkers	2007:2032	clinical glycan biomarkers	2007:2032	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	7	39	from	microscale	1395:1404	arg1	plate					1419:1423	a 96-well plate	1409:1423	a 96-well plate	1409:1423	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	7	39	from	microscale	1395:1404	arg1	tube					1444:1447	microcentrifuge tube	1428:1447	microcentrifuge tube	1428:1447	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	6	40	theme	various	1135:1141	arg1	plasma					1168:1173	human plasma	1162:1173	human plasma	1162:1173	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	40	theme	various	1135:1141	arg1	cells					1186:1190	mammalian cells	1176:1190	mammalian cells	1176:1190	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	40	theme	various	1135:1141	arg1	sources					1143:1149	various sources	1135:1149	various sources	1135:1149	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	40	theme	various	1135:1141	arg1	glycoproteins					1206:1218	purified glycoproteins	1197:1218	purified glycoproteins	1197:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	8	41	theme	tandem	1709:1714	arg1	acquisition					1719:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	0	42	theme	Micropermethylation	55:73	arg1	Strategy					75:82	a High-Throughput Micropermethylation Strategy	37:82	a High-Throughput Micropermethylation Strategy	37:82	Simplifying Glycan Profiling through a High-Throughput Micropermethylation Strategy.
32364434	10	43	theme	glycoprotein	2038:2049	arg1	therapeutics					2051:2062	glycoprotein therapeutics	2038:2062	glycoprotein therapeutics	2038:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	7	44	gly	glycoproteins	1360:1372	arg1	glycoproteins					1360:1372	glycoproteins	1360:1372	glycoproteins	1360:1372	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	7	45	from	plate	1419:1423	arg1	microscale					1395:1404	microscale	1395:1404	microscale	1395:1404	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	1	46	theme	non-template-driven	255:273	arg1	synthesis					275:283	non-template-driven synthesis	255:283	non-template-driven synthesis	255:283	Glycoproteins play key roles in various molecular and cellular functions and are among the most difficult to analyze biomolecules on account of their microheterogeneity, non-template-driven synthesis, and low abundances.
32364434	9	47	theme	workflow	1773:1780	arg1	utility					1757:1763	the utility	1753:1763	the utility of this workflow	1753:1780	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	4	48	theme	important	655:663	arg1	processes					680:688	the most important derivatization processes	646:688	the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS)	646:770	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	2	49	theme	therapeutic	381:391	arg1	biomarkers					444:453	biomarkers	444:453	biomarkers	444:453	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	49	theme	therapeutic	381:391	arg1	vaccines					430:437	vaccines	430:437	vaccines	430:437	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	49	theme	therapeutic	381:391	arg1	glycoproteins					393:405	therapeutic glycoproteins	381:405	therapeutic glycoproteins	381:405	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	2	49	theme	therapeutic	381:391	arg1	antibodies					418:427	antibodies	418:427	antibodies	418:427	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	1	50	theme	low	290:292	arg1	abundances					294:303	low abundances	290:303	low abundances	290:303	Glycoproteins play key roles in various molecular and cellular functions and are among the most difficult to analyze biomolecules on account of their microheterogeneity, non-template-driven synthesis, and low abundances.
32364434	10	51	gly	glycoprotein	2038:2049	arg1	glycoprotein					2038:2049	glycoprotein therapeutics	2038:2062	glycoprotein therapeutics	2038:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	9	52	theme	acid	1811:1814	arg1	linkages					1816:1823	sialic acid linkages	1804:1823	sialic acid linkages	1804:1823	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	6	53	theme	spectrometry	1278:1289	arg1	platform					1301:1308	an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform	1229:1308	an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform	1229:1308	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	3	54	theme	glycosylation	607:619	arg1	characterization					572:587	characterization	572:587	characterization	572:587	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	3	54	theme	glycosylation	607:619	arg1	validation					593:602	validation	593:602	validation	593:602	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	5	55	theme	sample	939:944	arg1	sets					946:949	large sample sets	933:949	large sample sets	933:949	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	6	56	theme	electrospray	1249:1260	arg1	ESI-MSn					1292:1298	ESI-MSn	1292:1298	ESI-MSn	1292:1298	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	56	theme	electrospray	1249:1260	arg1	spectrometry					1278:1289	an automated tandem electrospray ionization-mass spectrometry	1229:1289	an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform	1229:1308	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	4	57	theme	released	729:736	arg1	glycans					738:744	released glycans	729:744	released glycans	729:744	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	7	58	theme	simple	1511:1516	arg1	process					1518:1524	a shorter and simple process	1497:1524	a shorter and simple process	1497:1524	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	9	59	theme	GlcNAc	1839:1844	arg1	N-acetylglucosamine					1847:1865	bisecting GlcNAc (N-acetylglucosamine)	1829:1866	bisecting GlcNAc (N-acetylglucosamine) on the glycans	1829:1881	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	7	60	theme	shorter	1499:1505	arg1	process					1518:1524	a shorter and simple process	1497:1524	a shorter and simple process	1497:1524	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	4	61	theme	processes	680:688	arg1	One					639:641	One	639:641	One	639:641	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	4	61	theme	processes	680:688	arg1	processes					680:688	the most important derivatization processes	646:688	the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS)	646:770	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	2	62	theme	biological	358:367	arg1	activity					369:376	biological activity	358:376	biological activity	358:376	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	10	63	theme	large	1961:1965	arg1	sets					1974:1977	large sample sets	1961:1977	large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics	1961:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	63	theme	large	1961:1965	arg1	therapeutics					2051:2062	glycoprotein therapeutics	2038:2062	glycoprotein therapeutics	2038:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	63	theme	large	1961:1965	arg1	biomarkers					2023:2032	clinical glycan biomarkers	2007:2032	clinical glycan biomarkers	2007:2032	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	63	theme	large	1961:1965	arg1	glycoproteins					1982:1994	glycoproteins	1982:1994	glycoproteins	1982:1994	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	9	64	from	examples	1792:1799	arg1	glycans					1875:1881	the glycans	1871:1881	the glycans	1871:1881	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	9	65	from	N-acetylglucosamine	1847:1865	arg1	glycans					1875:1881	the glycans	1871:1881	the glycans	1871:1881	We have demonstrated the utility of this workflow using the examples of sialic acid linkages and bisecting GlcNAc (N-acetylglucosamine) on the glycans.
32364434	3	66	gly	glycoproteins	624:636	arg1	glycoproteins					624:636	glycoproteins	624:636	glycoproteins	624:636	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	10	67	theme	glycosylation	1944:1956	arg1	screening					1931:1939	the high-throughput screening	1911:1939	the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics	1911:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	5	68	from	processing	919:928	arg1	amounts					963:969	nanogram amounts	954:969	nanogram amounts	954:969	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	5	69	theme	high-throughput	979:993	arg1	handling					1002:1009	high-throughput sample handling	979:1009	high-throughput sample handling	979:1009	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	7	70	theme	tip-based	1471:1479	arg1	cleanup					1481:1487	a C18 tip-based cleanup	1465:1487	a C18 tip-based cleanup through a shorter and simple process	1465:1524	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	3	71	gly	glycosylation	607:619	arg1	glycoproteins					624:636	glycoproteins	624:636	glycoproteins	624:636	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	3	72	from	validation	593:602	arg1	glycoproteins					624:636	glycoproteins	624:636	glycoproteins	624:636	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	5	73	from	strategy	835:842	arg1	microscale					847:856	microscale	847:856	microscale	847:856	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	10	74	theme	glycoproteins	1982:1994	arg1	sets					1974:1977	large sample sets	1961:1977	large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics	1961:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	74	theme	glycoproteins	1982:1994	arg1	therapeutics					2051:2062	glycoprotein therapeutics	2038:2062	glycoprotein therapeutics	2038:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	74	theme	glycoproteins	1982:1994	arg1	biomarkers					2023:2032	clinical glycan biomarkers	2007:2032	clinical glycan biomarkers	2007:2032	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	74	theme	glycoproteins	1982:1994	arg1	glycoproteins					1982:1994	glycoproteins	1982:1994	glycoproteins	1982:1994	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	8	75	theme	automated	1582:1590	arg1	characterization					1603:1618	in-depth automated structural characterization	1573:1618	an in-depth automated structural characterization MS program for permethylated N/O-glycans	1570:1659	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	3	76	from	glycosylation	607:619	arg1	glycoproteins					624:636	glycoproteins	624:636	glycoproteins	624:636	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	8	77	theme	characterization	1603:1618	arg1	program					1623:1629	an in-depth automated structural characterization MS program	1570:1629	an in-depth automated structural characterization MS program for permethylated N/O-glycans	1570:1659	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	5	78	theme	permethylation	820:833	arg1	strategy					835:842	a permethylation strategy	818:842	a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling	818:1009	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	6	79	theme	structural	1099:1108	arg1	analysis					1110:1117	micropermethylation-based high-throughput structural analysis	1057:1117	micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1057:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	80	from	analysis	1110:1117	arg1	plasma					1168:1173	human plasma	1162:1173	human plasma	1162:1173	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	80	from	analysis	1110:1117	arg1	cells					1186:1190	mammalian cells	1176:1190	mammalian cells	1176:1190	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	80	from	analysis	1110:1117	arg1	sources					1143:1149	various sources	1135:1149	various sources	1135:1149	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	80	from	analysis	1110:1117	arg1	glycoproteins					1206:1218	purified glycoproteins	1197:1218	purified glycoproteins	1197:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	2	81	dep	stability	310:318	arg1	The					306:308	The	306:308	The	306:308	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	3	82	from	characterization	572:587	arg1	glycoproteins					624:636	glycoproteins	624:636	glycoproteins	624:636	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	6	83	theme	automated	1232:1240	arg1	ESI-MSn					1292:1298	ESI-MSn	1292:1298	ESI-MSn	1292:1298	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	83	theme	automated	1232:1240	arg1	spectrometry					1278:1289	an automated tandem electrospray ionization-mass spectrometry	1229:1289	an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform	1229:1308	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	6	84	theme	micropermethylation-based	1057:1081	arg1	analysis					1110:1117	micropermethylation-based high-throughput structural analysis	1057:1117	micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins	1057:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	8	85	theme	permethylated	1635:1647	arg1	N/O-glycans					1649:1659	permethylated N/O-glycans	1635:1659	permethylated N/O-glycans	1635:1659	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	6	86	theme	mammalian	1176:1184	arg1	cells					1186:1190	mammalian cells	1176:1190	mammalian cells	1176:1190	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	5	87	theme	facile	870:875	arg1	permethylation					877:890	facile permethylation	870:890	facile permethylation of glycans	870:901	We have recently developed a permethylation strategy in microscale that allows facile permethylation of glycans and permits the processing of large sample sets in nanogram amounts through high-throughput sample handling.
32364434	8	88	theme	automated	1672:1680	arg1	acquisition					1719:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	3	89	from	glycoproteins	624:636	arg1	characterization					572:587	characterization	572:587	characterization	572:587	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	3	89	from	glycoproteins	624:636	arg1	validation					593:602	validation	593:602	validation	593:602	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	1	90	theme	various	117:123	arg1	functions					148:156	various molecular and cellular functions	117:156	various molecular and cellular functions	117:156	Glycoproteins play key roles in various molecular and cellular functions and are among the most difficult to analyze biomolecules on account of their microheterogeneity, non-template-driven synthesis, and low abundances.
32364434	8	91	theme	multistage	1698:1707	arg1	acquisition					1719:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	10	92	theme	glycan	2016:2021	arg1	biomarkers					2023:2032	clinical glycan biomarkers	2007:2032	clinical glycan biomarkers	2007:2032	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	0	93	theme	High-Throughput	39:53	arg1	Strategy					75:82	a High-Throughput Micropermethylation Strategy	37:82	a High-Throughput Micropermethylation Strategy	37:82	Simplifying Glycan Profiling through a High-Throughput Micropermethylation Strategy.
32364434	7	94	theme	microcentrifuge	1428:1442	arg1	tube					1444:1447	microcentrifuge tube	1428:1447	microcentrifuge tube	1428:1447	The glycans released from the plasma, cells, and glycoproteins are permethylated in microscale in a 96-well plate or microcentrifuge tube and isolated by a C18 tip-based cleanup through a shorter and simple process.
32364434	8	95	theme	MS	1716:1717	arg1	acquisition					1719:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	an automated high-throughput multistage tandem MS acquisition	1669:1729	We have developed a workflow to accomplish an in-depth automated structural characterization MS program for permethylated N/O-glycans through an automated high-throughput multistage tandem MS acquisition.
32364434	2	96	theme	glycosylation	479:491	arg1	profile					493:499	their glycosylation profile	473:499	their glycosylation profile	473:499	The stability, serum half-life, immunogenicity, and biological activity of therapeutic glycoproteins, including antibodies, vaccines, and biomarkers, are regulated by their glycosylation profile.
32364434	3	97	theme	increasing	517:526	arg1	demand					528:533	increasing demand	517:533	increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins	517:636	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	3	98	theme	qualitative	543:553	arg1	characterization					572:587	characterization	572:587	characterization	572:587	Thus, there is increasing demand for the qualitative and quantitative characterization and validation of glycosylation on glycoproteins.
32364434	10	99	gly	glycoproteins	1982:1994	arg1	therapeutics					2051:2062	glycoprotein therapeutics	2038:2062	glycoprotein therapeutics	2038:2062	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	99	gly	glycoproteins	1982:1994	arg1	biomarkers					2023:2032	clinical glycan biomarkers	2007:2032	clinical glycan biomarkers	2007:2032	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	10	99	gly	glycoproteins	1982:1994	arg1	glycoproteins					1982:1994	glycoproteins	1982:1994	glycoproteins	1982:1994	This approach can automate the high-throughput screening of glycosylation on large sample sets of glycoproteins, including clinical glycan biomarkers and glycoprotein therapeutics.
32364434	6	100	theme	purified	1197:1204	arg1	glycoproteins					1206:1218	purified glycoproteins	1197:1218	purified glycoproteins	1197:1218	Here, we are reporting the wide potential of micropermethylation-based high-throughput structural analysis of glycans from various sources, including human plasma, mammalian cells, and purified glycoproteins, through an automated tandem electrospray ionization-mass spectrometry (ESI-MSn) platform.
32364434	4	101	theme	derivatization	665:678	arg1	processes					680:688	the most important derivatization processes	646:688	the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS)	646:770	One of the most important derivatization processes for the structural characterization of released glycans by mass spectrometry (MS) is permethylation.
32364434	0	102	theme	Glycan	12:17	arg1	Profiling					19:27	Glycan Profiling	12:27	Glycan Profiling	12:27	Simplifying Glycan Profiling through a High-Throughput Micropermethylation Strategy.
34944439	6	0	dep	transfer	973:980	arg1	O-glycans					1061:1069	O-glycans	1061:1069	O-glycans	1061:1069	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	3	1	theme	FucT	515:518	arg1	orthologs					520:528	the FucT orthologs	511:528	the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus	511:628	We studied the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus.
34944439	8	2	attach	links	1468:1472	arg2	FucT					1463:1466	the T. forsythia FucT	1446:1466	the T. forsythia FucT	1446:1466	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	8	2	attach	links	1468:1472	arg1	galactose					1491:1499	galactose	1491:1499	galactose	1491:1499	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	0	3	theme	Analyses	63:70	arg1	Combination					2:12	A Combination	0:12	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses	0:70	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	6	4	dep	ΔBF4306	1178:1184	arg1	transfer					973:980	the transfer	969:980	the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	969:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	4	dep	ΔBF4306	1178:1184	arg1	orthologs					1081:1089	the FucT orthologs	1072:1089	the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus	1072:1138	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	4	dep	ΔBF4306	1178:1184	arg1	the					1162:1164	the	1162:1164	the	1162:1164	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	4	dep	ΔBF4306	1178:1184	arg1	mutants					1220:1226	FucT mutants	1215:1226	FucT mutants	1215:1226	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	4	5	theme	full	709:712	arg1	structure					714:722	the full structure	705:722	the full structure of its nine-sugar O-glycan	705:749	To identify the linkage created by the FucT of B. fragilis, we elucidated the full structure of its nine-sugar O-glycan and found that l-fucose is linked β1,4 to glucose.
34944439	6	6	theme	l-fucose	985:992	arg1	transfer					973:980	the transfer	969:980	the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	969:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	6	theme	l-fucose	985:992	arg1	orthologs					1081:1089	the FucT orthologs	1072:1089	the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus	1072:1138	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	7	7	theme	enzymes	1306:1312	arg1	specificity					1281:1291	relaxed acceptor specificity	1264:1291	relaxed acceptor specificity of the three enzymes	1264:1312	In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses.
34944439	3	8	theme	forsythia	572:580	arg1	orthologs					520:528	the FucT orthologs	511:528	the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus	511:628	We studied the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus.
34944439	7	9	dep	In	1229:1230	arg1	vitro					1232:1236	vitro	1232:1236	vitro	1232:1236	In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses.
34944439	5	10	from	residues	820:827	arg1	forsythia&nbsp					839:852	the T. forsythia&nbsp	832:852	the T. forsythia&nbsp;O-glycan	832:861	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	6	11	from	sugars	1013:1018	arg1	fragilis					1030:1037	B. fragilis	1027:1037	B. fragilis	1027:1037	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	11	from	sugars	1013:1018	arg1	forsythia&nbsp					1046:1059	T. forsythia&nbsp	1043:1059	T. forsythia&nbsp	1043:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	9	12	theme	carbohydrates	1549:1561	arg1	importance					1523:1532	the biological importance	1508:1532	the biological importance of fucosylated carbohydrates	1508:1561	Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.
34944439	6	13	from	heparinus	1130:1138	arg1	transfer					973:980	the transfer	969:980	the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	969:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	13	from	heparinus	1130:1138	arg1	orthologs					1081:1089	the FucT orthologs	1072:1089	the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus	1072:1138	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	0	14	from	O-Glycosylation	140:154	arg1	Bacteroidetes					163:175	the Bacteroidetes	159:175	the Bacteroidetes	159:175	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	5	15	attach	linked	875:880	arg2	fucose					868:873	the fucose	864:873	the fucose linked to the reducing-end galactose	864:910	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	5	15	attach	linked	875:880	arg2	l-fucose					951:958	l-fucose	951:958	l-fucose	951:958	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	5	15	attach	linked	875:880	arg1	galactose					902:910	the reducing-end galactose	885:910	the reducing-end galactose	885:910	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	5	16	theme	T.	836:837	arg1	forsythia&nbsp					839:852	the T. forsythia&nbsp	832:852	the T. forsythia&nbsp;O-glycan	832:861	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	4	17	theme	fragilis	681:688	arg1	FucT					670:673	the FucT	666:673	the FucT of B. fragilis	666:688	To identify the linkage created by the FucT of B. fragilis, we elucidated the full structure of its nine-sugar O-glycan and found that l-fucose is linked β1,4 to glucose.
34944439	5	18	theme	reducing-end	889:900	arg1	galactose					902:910	the reducing-end galactose	885:910	the reducing-end galactose	885:910	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	6	19	dep	fragilis	1030:1037	arg1	the					1023:1025	the	1023:1025	the	1023:1025	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	1	20	theme	Diverse	178:184	arg1	members					186:192	Diverse members	178:192	Diverse members of the Bacteroidetes phylum	178:220	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	2	21	theme	Bacteroidetes	448:460	arg1	loci					494:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	5	22	theme	mutational	925:934	arg1	analysis					936:943	mutational analysis	925:943	mutational analysis	925:943	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	7	23	theme	enzymatic	1238:1246	arg1	analyses					1248:1255	In vitro enzymatic analyses	1229:1255	In vitro enzymatic analyses	1229:1255	In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses.
34944439	2	24	theme	fucosyltransferase	389:406	arg1	family					415:420	a putative fucosyltransferase (FucT) family	378:420	a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci	378:497	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	5	25	theme	fucose	813:818	arg1	residues					820:827	the two fucose residues	805:827	the two fucose residues in the T. forsythia&nbsp;O-glycan	805:861	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	6	26	theme	FucT	1215:1218	arg1	mutants					1220:1226	FucT mutants	1215:1226	FucT mutants	1215:1226	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	27	from	forsythia	1112:1120	arg1	transfer					973:980	the transfer	969:980	the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	969:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	27	from	forsythia	1112:1120	arg1	orthologs					1081:1089	the FucT orthologs	1072:1089	the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus	1072:1138	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	2	28	theme	putative	380:387	arg1	FucT					409:412	FucT	409:412	FucT	409:412	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	2	28	theme	putative	380:387	arg1	fucosyltransferase					389:406	putative fucosyltransferase	380:406	a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci	378:497	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	0	29	theme	Structural	17:26	arg1	Analyses					63:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	4	30	attach	linked	778:783	arg1	glucose					793:799	glucose	793:799	glucose	793:799	To identify the linkage created by the FucT of B. fragilis, we elucidated the full structure of its nine-sugar O-glycan and found that l-fucose is linked β1,4 to glucose.
34944439	4	30	attach	linked	778:783	arg2	l-fucose					766:773	l-fucose	766:773	l-fucose	766:773	To identify the linkage created by the FucT of B. fragilis, we elucidated the full structure of its nine-sugar O-glycan and found that l-fucose is linked β1,4 to glucose.
34944439	0	31	theme	Fucosyltransferase	110:127	arg1	Importance					84:93	the Importance	80:93	the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes	80:175	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	9	32	theme	promising	1580:1588	arg1	FucTs					1570:1574	these FucTs	1564:1574	these FucTs	1564:1574	Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.
34944439	9	32	theme	promising	1580:1588	arg1	candidates					1590:1599	promising candidates	1580:1599	promising candidates for synthetic glycobiology	1580:1626	Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.
34944439	9	33	gly	fucosylated	1537:1547	arg1	carbohydrates					1549:1561	fucosylated carbohydrates	1537:1561	fucosylated carbohydrates	1537:1561	Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.
34944439	0	34	theme	Predicted	100:108	arg1	Fucosyltransferase					110:127	a Predicted Fucosyltransferase	98:127	a Predicted Fucosyltransferase	98:127	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	8	35	theme	glycan	1372:1377	arg1	analysis					1390:1397	glycan structural analysis	1372:1397	glycan structural analysis together with fucosidase assays	1372:1429	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	3	36	theme	fragilis	595:602	arg1	orthologs					520:528	the FucT orthologs	511:528	the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus	511:628	We studied the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus.
34944439	1	37	theme	Bacteroidetes	201:213	arg1	members					186:192	Diverse members	178:192	Diverse members of the Bacteroidetes phylum	178:220	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	0	38	theme	Genetic	29:35	arg1	Analyses					63:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	1	39	theme	host	308:311	arg1	colonization					313:324	host colonization	308:324	host colonization	308:324	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	0	40	theme	Protein	132:138	arg1	O-Glycosylation					140:154	Protein O-Glycosylation	132:154	Protein O-Glycosylation in the Bacteroidetes	132:175	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	7	41	theme	relaxed	1264:1270	arg1	specificity					1281:1291	relaxed acceptor specificity	1264:1291	relaxed acceptor specificity of the three enzymes	1264:1312	In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses.
34944439	8	42	theme	structural	1379:1388	arg1	analysis					1390:1397	glycan structural analysis	1372:1397	glycan structural analysis together with fucosidase assays	1372:1429	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	6	43	theme	T.	1043:1044	arg1	forsythia&nbsp					1046:1059	T. forsythia&nbsp	1043:1059	T. forsythia&nbsp	1043:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	2	44	theme	family	415:420	arg1	function					366:373	the function	362:373	the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci	362:497	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	2	45	theme	genetic	486:492	arg1	loci					494:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	8	46	theme	forsythia	1453:1461	arg1	FucT					1463:1466	the T. forsythia FucT	1446:1466	the T. forsythia FucT	1446:1466	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	6	47	theme	hexose	1006:1011	arg1	sugars					1013:1018	distinct hexose sugars	997:1018	distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	997:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	7	48	theme	acceptor	1272:1279	arg1	specificity					1281:1291	relaxed acceptor specificity	1264:1291	relaxed acceptor specificity of the three enzymes	1264:1312	In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses.
34944439	0	49	theme	Phenotypic	38:47	arg1	Analyses					63:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	9	50	theme	synthetic	1605:1613	arg1	glycobiology					1615:1626	synthetic glycobiology	1605:1626	synthetic glycobiology	1605:1626	Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.
34944439	8	51	theme	T.	1450:1451	arg1	FucT					1463:1466	the T. forsythia FucT	1446:1466	the T. forsythia FucT	1446:1466	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	9	52	theme	biological	1512:1521	arg1	importance					1523:1532	the biological importance	1508:1532	the biological importance of fucosylated carbohydrates	1508:1561	Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.
34944439	6	53	dep	B.	1166:1167	arg1	fragilis					1169:1176	fragilis	1169:1176	fragilis	1169:1176	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	2	54	theme	protein	462:468	arg1	loci					494:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	1	55	contain	have	222:225	arg1	members					186:192	Diverse members	178:192	Diverse members of the Bacteroidetes phylum	178:220	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	1	55	contain	have	222:225	arg2	systems					259:265	general protein O-glycosylation systems	227:265	general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis	227:341	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	3	56	theme	heparinus	620:628	arg1	orthologs					520:528	the FucT orthologs	511:528	the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus	511:628	We studied the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus.
34944439	7	57	theme	In	1229:1230	arg1	analyses					1248:1255	In vitro enzymatic analyses	1229:1255	In vitro enzymatic analyses	1229:1255	In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses.
34944439	8	58	theme	fucosidase	1413:1422	arg1	assays					1424:1429	fucosidase assays	1413:1429	glycan structural analysis together with fucosidase assays	1372:1429	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	5	59	dep	forsythia&nbsp	839:852	arg1	O-glycan					854:861	O-glycan	854:861	the T. forsythia&nbsp;O-glycan	832:861	Of the two fucose residues in the T. forsythia&nbsp;O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose.
34944439	6	60	from	fragilis	1099:1106	arg1	transfer					973:980	the transfer	969:980	the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	969:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	60	from	fragilis	1099:1106	arg1	orthologs					1081:1089	the FucT orthologs	1072:1089	the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus	1072:1138	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	4	61	theme	O-glycan	742:749	arg1	structure					714:722	the full structure	705:722	the full structure of its nine-sugar O-glycan	705:749	To identify the linkage created by the FucT of B. fragilis, we elucidated the full structure of its nine-sugar O-glycan and found that l-fucose is linked β1,4 to glucose.
34944439	1	62	theme	general	227:233	arg1	systems					259:265	general protein O-glycosylation systems	227:265	general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis	227:341	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	9	63	theme	fucosylated	1537:1547	arg1	carbohydrates					1549:1561	fucosylated carbohydrates	1537:1561	fucosylated carbohydrates	1537:1561	Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.
34944439	6	64	theme	cross-complement	1145:1160	arg1	ΔBF4306					1178:1184	B. fragilis ΔBF4306	1166:1184	B. fragilis ΔBF4306	1166:1184	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	4	65	theme	nine-sugar	731:740	arg1	O-glycan					742:749	its nine-sugar O-glycan	727:749	its nine-sugar O-glycan	727:749	To identify the linkage created by the FucT of B. fragilis, we elucidated the full structure of its nine-sugar O-glycan and found that l-fucose is linked β1,4 to glucose.
34944439	1	66	theme	protein	235:241	arg1	systems					259:265	general protein O-glycosylation systems	227:265	general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis	227:341	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	0	67	theme	Enzymatic	53:61	arg1	Analyses					63:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	Structural, Genetic, Phenotypic and Enzymatic Analyses	17:70	A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.
34944439	8	68	theme	l-fucose	1474:1481	arg1	α1,6					1483:1486	l-fucose α1,6	1474:1486	l-fucose α1,6	1474:1486	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	6	69	theme	B.	1166:1167	arg1	ΔBF4306					1178:1184	B. fragilis ΔBF4306	1166:1184	B. fragilis ΔBF4306	1166:1184	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	8	70	dep	together	1399:1406	arg1	with					1408:1411	with	1408:1411	with	1408:1411	Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose.
34944439	1	71	theme	O-glycosylation	243:257	arg1	systems					259:265	general protein O-glycosylation systems	227:265	general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis	227:341	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	2	72	theme	O-glycosylation	470:484	arg1	loci					494:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Bacteroidetes protein O-glycosylation genetic loci	448:497	Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci.
34944439	7	73	theme	various	1340:1346	arg1	pNP-α-hexoses					1348:1360	various pNP-α-hexoses	1340:1360	various pNP-α-hexoses	1340:1360	In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses.
34944439	1	74	dep	Bacteroidetes	201:213	arg1	phylum					215:220	phylum	215:220	phylum	215:220	Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis.
34944439	6	75	theme	FucT	1076:1079	arg1	transfer					973:980	the transfer	969:980	the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	969:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	75	theme	FucT	1076:1079	arg1	orthologs					1081:1089	the FucT orthologs	1072:1089	the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus	1072:1138	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
34944439	6	76	theme	distinct	997:1004	arg1	sugars					1013:1018	distinct hexose sugars	997:1018	distinct hexose sugars in the B. fragilis and T. forsythia&nbsp	997:1059	Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia&nbsp;O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants.
32220931	1	0	gly	Fucosylation	81:92	arg1	GlcNAc					111:116	the innermost GlcNAc	97:116	the innermost GlcNAc of N-glycans	97:129	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	2	1	theme	glycosylation	474:486	arg1	disorder					488:495	a congenital glycosylation disorder	461:495	a congenital glycosylation disorder	461:495	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	4	2	from	structures	796:805	arg1	state					842:846	the apo state	834:846	the apo state	834:846	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	4	2	from	structures	796:805	arg1	complex					855:861	complex	855:861	complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	855:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	2	3	theme	congenital	463:472	arg1	disorder					488:495	a congenital glycosylation disorder	461:495	a congenital glycosylation disorder	461:495	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	3	4	theme	preferences	689:699	arg1	mechanism					709:717	the mechanism	705:717	the mechanism through which catalysis is achieved	705:753	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	3	4	theme	preferences	689:699	arg1	basis					664:668	the structural basis	649:668	the structural basis of these substrate preferences	649:699	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	3	5	theme	acceptor	502:509	arg1	well-characterized					545:562	well-characterized	545:562	well-characterized	545:562	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	3	5	theme	acceptor	502:509	arg1	preferences					521:531	The acceptor substrate preferences	498:531	The acceptor substrate preferences of FUT8	498:539	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	7	6	theme	fucosylation	1508:1519	arg1	process					1521:1527	the core fucosylation process	1499:1527	the core fucosylation process	1499:1527	Collectively, this information significantly builds on our understanding of the core fucosylation process.
32220931	6	7	theme	dynamics	1277:1284	arg1	simulations					1286:1296	molecular dynamics simulations	1267:1296	molecular dynamics simulations	1267:1296	Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site.
32220931	5	8	theme	likely	1214:1219	arg1	mechanism					1221:1229	a likely mechanism	1212:1229	a likely mechanism for enzyme catalysis	1212:1250	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	4	9	theme	acceptor	929:936	arg1	substrate					938:946	a glycopeptide acceptor substrate	914:946	a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	914:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	5	10	theme	common	1086:1091	arg1	strategies					1093:1102	common strategies	1086:1102	common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis	1086:1250	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	5	10	theme	common	1086:1091	arg1	binding					1077:1083	donor substrate binding	1061:1083	donor substrate binding	1061:1083	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	6	11	theme	molecular	1267:1275	arg1	simulations					1286:1296	molecular dynamics simulations	1267:1296	molecular dynamics simulations	1267:1296	Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site.
32220931	4	12	theme	several	788:794	arg1	structures					796:805	several structures	788:805	several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	788:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	6	13	theme	acceptor	1390:1397	arg1	site					1417:1420	the acceptor substrate-binding site	1386:1420	the acceptor substrate-binding site	1386:1420	Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site.
32220931	4	14	theme	glycopeptide	916:927	arg1	substrate					938:946	a glycopeptide acceptor substrate	914:946	a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	914:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	4	15	theme	apo	838:840	arg1	state					842:846	the apo state	834:846	the apo state	834:846	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	3	16	theme	FUT8	536:539	arg1	well-characterized					545:562	well-characterized	545:562	well-characterized	545:562	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	3	16	theme	FUT8	536:539	arg1	preferences					521:531	The acceptor substrate preferences	498:531	The acceptor substrate preferences of FUT8	498:539	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	4	17	dep	a	873:873	arg1	mimic					875:879	mimic	875:879	mimic	875:879	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	1	18	theme	important	168:176	arg1	step					178:181	an important step	165:181	an important step in the maturation of complex and hybrid N-glycans	165:231	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	1	18	theme	important	168:176	arg1	Fucosylation					81:92	Fucosylation	81:92	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8)	81:160	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	0	19	theme	Structural	0:9	arg1	basis					11:15	Structural basis	0:15	Structural basis of substrate recognition and catalysis by fucosyltransferase 8.	0:79	Structural basis of substrate recognition and catalysis by fucosyltransferase 8.
32220931	5	20	theme	donor	1061:1065	arg1	strategies					1093:1102	common strategies	1086:1102	common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis	1086:1250	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	5	20	theme	donor	1061:1065	arg1	binding					1077:1083	donor substrate binding	1061:1083	donor substrate binding	1061:1083	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	0	21	theme	substrate	20:28	arg1	recognition					30:40	substrate recognition	20:40	substrate recognition	20:40	Structural basis of substrate recognition and catalysis by fucosyltransferase 8.
32220931	5	22	theme	acceptor	1176:1183	arg1	preferences					1195:1205	acceptor substrate preferences	1176:1205	acceptor substrate preferences	1176:1205	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	6	23	theme	important	1359:1367	arg1	role					1369:1372	an important role	1356:1372	an important role	1356:1372	Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site.
32220931	1	24	theme	innermost	101:109	arg1	GlcNAc					111:116	the innermost GlcNAc	97:116	the innermost GlcNAc of N-glycans	97:129	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	4	25	theme	FUT8	826:829	arg1	structures					796:805	several structures	788:805	several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	788:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	2	26	theme	mAb	423:425	arg1	therapeutics					427:438	mAb therapeutics	423:438	mAb therapeutics	423:438	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	5	27	theme	substrate	1185:1193	arg1	preferences					1195:1205	acceptor substrate preferences	1176:1205	acceptor substrate preferences	1176:1205	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	4	28	theme	donor	888:892	arg1	substrate					894:902	the donor substrate	884:902	the donor substrate	884:902	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	1	29	theme	GlcNAc	111:116	arg1	Fucosylation					81:92	Fucosylation	81:92	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8)	81:160	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	1	29	theme	GlcNAc	111:116	arg1	step					178:181	an important step	165:181	an important step in the maturation of complex and hybrid N-glycans	165:231	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	2	30	dep	activities	287:296	arg1	the					283:285	the	283:285	the	283:285	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	3	31	theme	structural	653:662	arg1	basis					664:668	the structural basis	649:668	the structural basis of these substrate preferences	649:699	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	3	32	theme	N-glycan	606:613	arg1	maturation					615:624	N-glycan maturation	606:624	N-glycan maturation	606:624	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	0	33	theme	recognition	30:40	arg1	basis					11:15	Structural basis	0:15	Structural basis of substrate recognition and catalysis by fucosyltransferase 8.	0:79	Structural basis of substrate recognition and catalysis by fucosyltransferase 8.
32220931	7	34	theme	core	1503:1506	arg1	process					1521:1527	the core fucosylation process	1499:1527	the core fucosylation process	1499:1527	Collectively, this information significantly builds on our understanding of the core fucosylation process.
32220931	6	35	theme	FUT8	1332:1335	arg1	dimerization					1337:1348	FUT8 dimerization	1332:1348	FUT8 dimerization	1332:1348	Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site.
32220931	5	36	theme	substrate	1067:1075	arg1	strategies					1093:1102	common strategies	1086:1102	common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis	1086:1250	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	5	36	theme	substrate	1067:1075	arg1	binding					1077:1083	donor substrate binding	1061:1083	donor substrate binding	1061:1083	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	2	37	theme	therapeutics	427:438	arg1	etiology					449:456	the etiology	445:456	the etiology of a congenital glycosylation disorder	445:495	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	37	theme	therapeutics	427:438	arg1	development					408:418	development	408:418	development of mAb therapeutics	408:438	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	37	theme	therapeutics	427:438	arg1	invasiveness					378:389	the invasiveness	374:389	the invasiveness of some cancers	374:405	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	38	theme	cancers	399:405	arg1	etiology					449:456	the etiology	445:456	the etiology of a congenital glycosylation disorder	445:495	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	38	theme	cancers	399:405	arg1	development					408:418	development	408:418	development of mAb therapeutics	408:438	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	38	theme	cancers	399:405	arg1	invasiveness					378:389	the invasiveness	374:389	the invasiveness of some cancers	374:405	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	6	39	theme	substrate-binding	1399:1415	arg1	site					1417:1420	the acceptor substrate-binding site	1386:1420	the acceptor substrate-binding site	1386:1420	Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site.
32220931	0	40	theme	catalysis	46:54	arg1	basis					11:15	Structural basis	0:15	Structural basis of substrate recognition and catalysis by fucosyltransferase 8.	0:79	Structural basis of substrate recognition and catalysis by fucosyltransferase 8.
32220931	7	41	theme	process	1521:1527	arg1	understanding					1482:1494	our understanding	1478:1494	our understanding of the core fucosylation process	1478:1527	Collectively, this information significantly builds on our understanding of the core fucosylation process.
32220931	5	42	theme	unique	1016:1021	arg1	change					1038:1043	a unique conformational change	1014:1043	a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis	1014:1250	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	5	43	theme	conformational	1023:1036	arg1	change					1038:1043	a unique conformational change	1014:1043	a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis	1014:1250	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	1	44	theme	N-glycans	121:129	arg1	GlcNAc					111:116	the innermost GlcNAc	97:116	the innermost GlcNAc of N-glycans	97:129	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	4	45	from	resolution	963:972	arg1	substrate					938:946	a glycopeptide acceptor substrate	914:946	a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	914:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	2	46	gly	glycoproteins	316:328	arg1	glycoproteins					316:328	glycoproteins	316:328	glycoproteins	316:328	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	3	47	theme	substrate	679:687	arg1	preferences					689:699	these substrate preferences	673:699	these substrate preferences	673:699	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	4	48	theme	human	820:824	arg1	FUT8					826:829	human FUT8	820:829	human FUT8	820:829	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	4	49	gly	glycopeptide	916:927	arg2	glycopeptide					916:927	glycopeptide	916:927	glycopeptide	916:927	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	1	50	theme	complex	204:210	arg1	maturation					190:199	the maturation	186:199	the maturation of complex and hybrid N-glycans	186:231	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	2	51	theme	simple	239:244	arg1	modification					246:257	This simple modification	234:257	This simple modification	234:257	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	52	theme	glycoproteins	316:328	arg1	effects					331:337	effects	331:337	effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder	331:495	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	52	theme	glycoproteins	316:328	arg1	half-lives					302:311	half-lives	302:311	half-lives	302:311	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	52	theme	glycoproteins	316:328	arg1	activities					287:296	activities	287:296	activities	287:296	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	1	53	from	step	178:181	arg1	maturation					190:199	the maturation	186:199	the maturation of complex and hybrid N-glycans	186:231	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	3	54	theme	substrate	511:519	arg1	well-characterized					545:562	well-characterized	545:562	well-characterized	545:562	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	3	54	theme	substrate	511:519	arg1	preferences					521:531	The acceptor substrate preferences	498:531	The acceptor substrate preferences of FUT8	498:539	The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown.
32220931	4	55	with	complex	855:861	arg1	a					873:873	a	873:873	a	873:873	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	4	55	with	complex	855:861	arg1	GDP					868:870	GDP	868:870	GDP	868:870	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	4	55	with	complex	855:861	arg1	substrate					938:946	a glycopeptide acceptor substrate	914:946	a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	914:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	1	56	theme	hybrid	216:221	arg1	N-glycans					223:231	hybrid N-glycans	216:231	hybrid N-glycans	216:231	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
32220931	2	57	theme	disorder	488:495	arg1	etiology					449:456	the etiology	445:456	the etiology of a congenital glycosylation disorder	445:495	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	57	theme	disorder	488:495	arg1	development					408:418	development	408:418	development of mAb therapeutics	408:438	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	2	57	theme	disorder	488:495	arg1	invasiveness					378:389	the invasiveness	374:389	the invasiveness of some cancers	374:405	This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder.
32220931	4	58	theme	Å	961:961	arg1	resolution					963:972	1.80-2.50 Å resolution	951:972	1.80-2.50 Å resolution	951:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	4	59	theme	mouse	810:814	arg1	structures					796:805	several structures	788:805	several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution	788:972	Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 Å resolution.
32220931	5	60	theme	enzyme	1235:1240	arg1	catalysis					1242:1250	enzyme catalysis	1235:1250	enzyme catalysis	1235:1250	These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis.
32220931	1	61	theme	N-glycans	223:231	arg1	maturation					190:199	the maturation	186:199	the maturation of complex and hybrid N-glycans	186:231	Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans.
33167210	7	0	theme	high	1235:1238	arg1	structures					1253:1262	hybrid-type and high mannose-type structures	1219:1262	hybrid-type and high mannose-type structures	1219:1262	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	7	0	theme	high	1235:1238	arg1	motives					1189:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	0	1	from	profiling	29:37	arg1	plasma					81:86	seminal plasma	73:86	seminal plasma	73:86	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	7	2	theme	N	1154:1154	arg1	structures					1253:1262	hybrid-type and high mannose-type structures	1219:1262	hybrid-type and high mannose-type structures	1219:1262	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	7	2	theme	N	1154:1154	arg1	motives					1189:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	1	3	theme	male	172:175	arg1	infertility					177:187	male infertility	172:187	male infertility	172:187	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	7	4	theme	mannose-type	1240:1251	arg1	structures					1253:1262	hybrid-type and high mannose-type structures	1219:1262	hybrid-type and high mannose-type structures	1219:1262	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	7	4	theme	mannose-type	1240:1251	arg1	motives					1189:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	3	5	from	involvement	411:421	arg1	process					465:471	the fertilization process	447:471	the fertilization process	447:471	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	8	6	theme	intra-	1290:1295	arg1	repeatability					1310:1322	a high intra- and interday repeatability	1283:1322	a high intra- and interday repeatability	1283:1322	Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men.
33167210	4	7	theme	glycopeptide	684:695	arg1	workflow					697:704	a novel, high-throughput PSA glycopeptide workflow	655:704	a novel, high-throughput PSA glycopeptide workflow	655:704	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	4	8	theme	desorption/ionization-mass	738:763	arg1	spectrometry					765:776	matrix-assisted laser desorption/ionization-mass spectrometry	716:776	matrix-assisted laser desorption/ionization-mass spectrometry	716:776	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	6	9	theme	sialylation	1128:1138	arg1	levels					1101:1106	high levels	1096:1106	high levels of fucosylation and sialylation	1096:1138	Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation.
33167210	4	10	dep	novel	657:661	arg1	high-throughput					664:678	high-throughput	664:678	high-throughput	664:678	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	3	11	with	glycosylation	519:531	arg1	resolution					582:591	a high glycoform resolution	565:591	a high glycoform resolution	565:591	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	2	12	from	role	335:338	arg1	fertility					369:377	male fertility	364:377	male fertility	364:377	However, the exact role of PSA glycosylation in male fertility is not clear.
33167210	3	13	theme	seminal	545:551	arg1	plasma					553:558	seminal plasma	545:558	seminal plasma	545:558	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	14	from	plasma	553:558	arg1	PSA					536:538	PSA	536:538	PSA from seminal plasma	536:558	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	14	from	plasma	553:558	arg1	glycosylation					519:531	the glycosylation	515:531	the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner	515:624	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	15	theme	high	567:570	arg1	resolution					582:591	a high glycoform resolution	565:591	a high glycoform resolution	565:591	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	16	gly	glycosylation	519:531	arg1	manner					619:624	a protein-specific manner	600:624	a protein-specific manner	600:624	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	16	gly	glycosylation	519:531	arg1	PSA					536:538	PSA	536:538	PSA from seminal plasma	536:558	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	17	from	glycosylation	519:531	arg1	manner					619:624	a protein-specific manner	600:624	a protein-specific manner	600:624	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	17	from	glycosylation	519:531	arg1	plasma					553:558	seminal plasma	545:558	seminal plasma	545:558	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	2	18	theme	male	364:367	arg1	fertility					369:377	male fertility	364:377	male fertility	364:377	However, the exact role of PSA glycosylation in male fertility is not clear.
33167210	1	19	theme	important	283:291	arg1	role					293:296	an important role	280:296	an important role	280:296	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	1	20	theme	plasma	126:131	arg1	glycosylation					133:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	3	21	theme	analytical	474:483	arg1	methods					485:491	analytical methods	474:491	analytical methods	474:491	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	3	22	theme	PSA	536:538	arg1	glycosylation					519:531	the glycosylation	515:531	the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner	515:624	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	6	23	theme	fucosylation	1111:1122	arg1	levels					1101:1106	high levels	1096:1106	high levels of fucosylation and sialylation	1096:1138	Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation.
33167210	4	24	theme	isomers	830:836	arg1	discrimination					792:805	the discrimination	788:805	the discrimination of sialic acid linkage isomers	788:836	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	0	25	theme	glycopeptide	16:27	arg1	profiling					29:37	High-throughput glycopeptide profiling	0:37	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS	0:98	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	1	26	gly	glycoprotein	229:240	arg1	glycoprotein					229:240	the highly abundant seminal plasma glycoprotein prostate-specific antigen	194:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA)	194:272	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	7	27	located	found	1202:1206	arg2	structures					1253:1262	hybrid-type and high mannose-type structures	1219:1262	hybrid-type and high mannose-type structures	1219:1262	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	7	27	located	found	1202:1206	arg2	motives					1189:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	7	27	located	found	1202:1206	arg1	addition					1144:1151	addition	1144:1151	addition	1144:1151	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	2	28	theme	exact	329:333	arg1	role					335:338	the exact role	325:338	the exact role of PSA glycosylation in male fertility	325:377	However, the exact role of PSA glycosylation in male fertility is not clear.
33167210	2	28	theme	exact	329:333	arg1	clear					386:390	clear	386:390	clear	386:390	However, the exact role of PSA glycosylation in male fertility is not clear.
33167210	3	29	theme	PSA	426:428	arg1	glycosylation					430:442	PSA glycosylation	426:442	PSA glycosylation	426:442	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	0	30	theme	High-throughput	0:14	arg1	profiling					29:37	High-throughput glycopeptide profiling	0:37	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS	0:98	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	6	31	theme	Forty-four	998:1007	arg1	glycopeptides					1009:1021	Forty-four glycopeptides	998:1021	Forty-four glycopeptides	998:1021	Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation.
33167210	1	32	theme	altered	104:110	arg1	glycosylation					133:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	8	33	theme	infertile	1392:1400	arg1	men					1402:1404	fertile and infertile men	1380:1404	fertile and infertile men	1380:1404	Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men.
33167210	3	34	theme	glycosylation	430:442	arg1	involvement					411:421	the involvement	407:421	the involvement of PSA glycosylation in the fertilization process	407:471	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	4	35	theme	laser	732:736	arg1	spectrometry					765:776	matrix-assisted laser desorption/ionization-mass spectrometry	716:776	matrix-assisted laser desorption/ionization-mass spectrometry	716:776	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	8	36	from	difference	1340:1349	arg1	glycosylation					1358:1370	PSA glycosylation	1354:1370	PSA glycosylation	1354:1370	Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men.
33167210	1	37	theme	total	112:116	arg1	glycosylation					133:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	1	38	theme	abundant	205:212	arg1	PSA					269:271	PSA	269:271	PSA	269:271	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	1	38	theme	abundant	205:212	arg1	antigen					260:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen	194:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA)	194:272	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	3	39	theme	glycoform	572:580	arg1	resolution					582:591	a high glycoform resolution	565:591	a high glycoform resolution	565:591	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	5	40	theme	fertile	975:981	arg1	men					983:985	men	983:985	infertile and fertile men (N = 102)	961:995	The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102).
33167210	5	40	theme	fertile	975:981	arg1	N = 102					988:994	N = 102	988:994	N = 102	988:994	The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102).
33167210	1	41	theme	seminal	118:124	arg1	glycosylation					133:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation	101:145	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	9	42	theme	disease	1548:1554	arg1	contexts					1556:1563	other disease contexts	1542:1563	other disease contexts	1542:1563	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	1	43	theme	seminal	214:220	arg1	PSA					269:271	PSA	269:271	PSA	269:271	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	1	43	theme	seminal	214:220	arg1	antigen					260:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen	194:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA)	194:272	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	0	44	theme	antigen	60:66	arg1	profiling					29:37	High-throughput glycopeptide profiling	0:37	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS	0:98	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	8	45	theme	PSA	1354:1356	arg1	glycosylation					1358:1370	PSA glycosylation	1354:1370	PSA glycosylation	1354:1370	Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men.
33167210	3	46	theme	fertilization	451:463	arg1	process					465:471	the fertilization process	447:471	the fertilization process	447:471	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	8	47	theme	high	1285:1288	arg1	repeatability					1310:1322	a high intra- and interday repeatability	1283:1322	a high intra- and interday repeatability	1283:1322	Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men.
33167210	4	48	theme	novel	657:661	arg1	workflow					697:704	a novel, high-throughput PSA glycopeptide workflow	655:704	a novel, high-throughput PSA glycopeptide workflow	655:704	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	1	49	theme	plasma	222:227	arg1	PSA					269:271	PSA	269:271	PSA	269:271	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	1	49	theme	plasma	222:227	arg1	antigen					260:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen	194:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA)	194:272	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	0	50	theme	prostate-specific	42:58	arg1	antigen					60:66	prostate-specific antigen	42:66	prostate-specific antigen from seminal plasma	42:86	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	8	51	theme	interday	1301:1308	arg1	repeatability					1310:1322	a high intra- and interday repeatability	1283:1322	a high intra- and interday repeatability	1283:1322	Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men.
33167210	0	52	gly	glycopeptide	16:27	arg2	glycopeptide					16:27	High-throughput glycopeptide profiling	0:37	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS	0:98	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	9	53	attach	derived	1503:1509	arg2	glycopeptides					1489:1501	PSA glycopeptides	1485:1501	PSA glycopeptides derived from other biofluids and/or in other disease contexts	1485:1563	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	9	53	attach	derived	1503:1509	arg1	biofluids					1522:1530	other biofluids	1516:1530	other biofluids	1516:1530	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	1	54	theme	glycoprotein	229:240	arg1	PSA					269:271	PSA	269:271	PSA	269:271	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	1	54	theme	glycoprotein	229:240	arg1	antigen					260:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen	194:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA)	194:272	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	0	55	theme	seminal	73:79	arg1	plasma					81:86	seminal plasma	73:86	seminal plasma	73:86	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	7	56	theme	hybrid-type	1219:1229	arg1	structures					1253:1262	hybrid-type and high mannose-type structures	1219:1262	hybrid-type and high mannose-type structures	1219:1262	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	7	56	theme	hybrid-type	1219:1229	arg1	motives					1189:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	N,N-diacetyllactosamine (LacdiNAc) motives	1154:1195	In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures.
33167210	8	57	theme	fertile	1380:1386	arg1	men					1402:1404	fertile and infertile men	1380:1404	fertile and infertile men	1380:1404	Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men.
33167210	0	58	from	plasma	81:86	arg1	profiling					29:37	High-throughput glycopeptide profiling	0:37	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS	0:98	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	0	58	from	plasma	81:86	arg1	antigen					60:66	prostate-specific antigen	42:66	prostate-specific antigen from seminal plasma	42:86	High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.
33167210	9	59	theme	PSA	1485:1487	arg1	glycopeptides					1489:1501	PSA glycopeptides	1485:1501	PSA glycopeptides derived from other biofluids and/or in other disease contexts	1485:1563	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	9	60	gly	glycopeptides	1489:1501	arg2	glycopeptides					1489:1501	PSA glycopeptides	1485:1501	PSA glycopeptides derived from other biofluids and/or in other disease contexts	1485:1563	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	2	61	theme	glycosylation	347:359	arg1	role					335:338	the exact role	325:338	the exact role of PSA glycosylation in male fertility	325:377	However, the exact role of PSA glycosylation in male fertility is not clear.
33167210	2	61	theme	glycosylation	347:359	arg1	clear					386:390	clear	386:390	clear	386:390	However, the exact role of PSA glycosylation in male fertility is not clear.
33167210	6	62	theme	high	1096:1099	arg1	levels					1101:1106	high levels	1096:1106	high levels of fucosylation and sialylation	1096:1138	Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation.
33167210	4	63	theme	glycopeptides	864:876	arg1	derivatization					846:859	the derivatization	842:859	the derivatization of glycopeptides	842:876	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	6	64	gly	glycopeptides	1009:1021	arg2	glycopeptides					1009:1021	Forty-four glycopeptides	998:1021	Forty-four glycopeptides	998:1021	Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation.
33167210	2	65	theme	PSA	343:345	arg1	glycosylation					347:359	PSA glycosylation	343:359	PSA glycosylation	343:359	However, the exact role of PSA glycosylation in male fertility is not clear.
33167210	5	66	from	men	983:985	arg1	plasma					949:954	seminal plasma	941:954	seminal plasma from infertile and fertile men (N = 102)	941:995	The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102).
33167210	4	67	gly	glycopeptide	684:695	arg2	glycopeptide					684:695	a novel, high-throughput PSA glycopeptide workflow	655:704	a novel, high-throughput PSA glycopeptide workflow	655:704	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	4	68	theme	acid	817:820	arg1	isomers					830:836	sialic acid linkage isomers	810:836	sialic acid linkage isomers	810:836	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	4	69	theme	matrix-assisted	716:730	arg1	spectrometry					765:776	matrix-assisted laser desorption/ionization-mass spectrometry	716:776	matrix-assisted laser desorption/ionization-mass spectrometry	716:776	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	1	70	theme	prostate-specific	242:258	arg1	PSA					269:271	PSA	269:271	PSA	269:271	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	1	70	theme	prostate-specific	242:258	arg1	antigen					260:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen	194:266	the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA)	194:272	An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization.
33167210	5	71	theme	seminal	941:947	arg1	plasma					949:954	seminal plasma	941:954	seminal plasma from infertile and fertile men (N = 102)	941:995	The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102).
33167210	4	72	theme	sialic	810:815	arg1	isomers					830:836	sialic acid linkage isomers	810:836	sialic acid linkage isomers	810:836	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	5	73	theme	infertile	961:969	arg1	men					983:985	men	983:985	infertile and fertile men (N = 102)	961:995	The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102).
33167210	5	73	theme	infertile	961:969	arg1	N = 102					988:994	N = 102	988:994	N = 102	988:994	The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102).
33167210	9	74	theme	other	1516:1520	arg1	biofluids					1522:1530	other biofluids	1516:1530	other biofluids	1516:1530	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	3	75	theme	protein-specific	602:617	arg1	manner					619:624	a protein-specific manner	600:624	a protein-specific manner	600:624	To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner.
33167210	4	76	gly	glycopeptides	864:876	arg2	glycopeptides					864:876	glycopeptides	864:876	glycopeptides	864:876	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	4	77	theme	PSA	680:682	arg1	workflow					697:704	a novel, high-throughput PSA glycopeptide workflow	655:704	a novel, high-throughput PSA glycopeptide workflow	655:704	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	9	78	theme	other	1542:1546	arg1	contexts					1556:1563	other disease contexts	1542:1563	other disease contexts	1542:1563	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	4	79	theme	linkage	822:828	arg1	isomers					830:836	sialic acid linkage isomers	810:836	sialic acid linkage isomers	810:836	In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides.
33167210	9	80	theme	seminal	1415:1421	arg1	plasma					1423:1428	seminal plasma	1415:1428	seminal plasma	1415:1428	Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
33167210	6	81	theme	complex-type	1070:1081	arg1	glycans					1083:1089	mainly complex-type glycans	1063:1089	mainly complex-type glycans	1063:1089	Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation.
34809984	0	0	theme	labeling	83:90	arg1	dyes					92:95	three labeling dyes	77:95	three labeling dyes	77:95	Cross-identification of N-Glycans by CE-LIF using two capillary coatings and three labeling dyes.
34809984	7	1	theme	glycans	1250:1256	arg1	identification					1232:1245	the identification	1228:1245	the identification of glycans	1228:1256	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	5	2	theme	separation	670:679	arg1	capabilities					681:692	complementary separation capabilities	656:692	complementary separation capabilities	656:692	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	8	3	theme	internal	1359:1366	arg1	standards					1368:1376	internal standards	1359:1376	the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer	1355:1453	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	4	4	theme	CE-LIF	534:539	arg1	method					541:546	CE-LIF method	534:546	CE-LIF method using two capillary coatings and three labeling dyes	534:599	To overcome this challenge in achieving accurate glycan identification, cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes was developed in this work.
34809984	6	5	theme	separation	837:846	arg1	profiles					848:855	Similar separation profiles	829:855	Similar separation profiles	829:855	Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary.
34809984	1	6	theme	current	175:181	arg1	landscape					200:208	the current drug development landscape	171:208	the current drug development landscape	171:208	Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape.
34809984	7	7	with	labeling	1043:1050	arg1	dyes					1075:1078	three fluorescent dyes	1057:1078	three fluorescent dyes	1057:1078	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	6	8	theme	N-glycan	919:926	arg1	databases					931:939	the N-glycan GU databases	915:939	the N-glycan GU databases generated by these coatings	915:967	Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary.
34809984	6	8	theme	N-glycan	919:926	arg1	comparable					974:983	comparable	974:983	comparable	974:983	Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary.
34809984	6	9	theme	Similar	829:835	arg1	profiles					848:855	Similar separation profiles	829:855	Similar separation profiles	829:855	Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary.
34809984	8	10	theme	maltodextrin	1396:1407	arg1	additives					1420:1428	additives	1420:1428	additives in the separation buffer	1420:1453	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	8	10	theme	maltodextrin	1396:1407	arg1	ladders					1409:1415	maltodextrin ladders	1396:1415	maltodextrin ladders	1396:1415	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	8	11	theme	standards	1368:1376	arg1	method					1383:1388	the internal standards (IS) method	1355:1388	the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer	1355:1453	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	5	12	theme	commercial	761:770	arg1	Guarant					782:788	Guarant	782:788	Guarant	782:788	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	5	12	theme	commercial	761:770	arg1	Guarant™					772:779	commercial Guarant™	761:779	commercial Guarant™ (Guarant)	761:789	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	4	13	theme	glycan	474:479	arg1	identification					481:494	accurate glycan identification	465:494	accurate glycan identification	465:494	To overcome this challenge in achieving accurate glycan identification, cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes was developed in this work.
34809984	7	14	theme	labeling	1133:1140	arg1	covariance					1099:1108	low covariance	1095:1108	low covariance of APTS and Turquoise™ labeling	1095:1140	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	9	15	theme	analysis	1477:1484	arg1	method					1486:1491	The developed CE-LIF analysis method	1456:1491	The developed CE-LIF analysis method	1456:1491	The developed CE-LIF analysis method was applied to the identification of N-glycans in IgG samples.
34809984	1	16	theme	drug	183:186	arg1	landscape					200:208	the current drug development landscape	171:208	the current drug development landscape	171:208	Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape.
34809984	3	17	theme	glycan	347:352	arg1	analysis					354:361	glycan analysis	347:361	glycan analysis	347:361	However, glycan analysis is challenging because of the complexity of their structures.
34809984	8	18	from	additives	1420:1428	arg1	buffer					1448:1453	the separation buffer	1433:1453	the separation buffer	1433:1453	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	1	19	theme	development	188:198	arg1	landscape					200:208	the current drug development landscape	171:208	the current drug development landscape	171:208	Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape.
34809984	5	20	theme	N-glycans	818:826	arg1	analysis					806:813	the analysis	802:813	the analysis of N-glycans	802:826	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	1	21	theme	landscape	200:208	arg1	portion					160:166	a significant portion	146:166	a significant portion of the current drug development landscape	146:208	Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape.
34809984	6	22	theme	GU	928:929	arg1	databases					931:939	the N-glycan GU databases	915:939	the N-glycan GU databases generated by these coatings	915:967	Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary.
34809984	6	22	theme	GU	928:929	arg1	comparable					974:983	comparable	974:983	comparable	974:983	Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary.
34809984	5	23	theme	complementary	656:668	arg1	capabilities					681:692	complementary separation capabilities	656:692	complementary separation capabilities	656:692	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	9	24	from	identification	1512:1525	arg1	samples					1547:1553	IgG samples	1543:1553	IgG samples	1543:1553	The developed CE-LIF analysis method was applied to the identification of N-glycans in IgG samples.
34809984	2	25	dep	parameter	272:280	arg1	affect					292:297	affect	292:297	can affect their safety, efficacy, and stability	288:335	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	5	26	theme	alcohol	735:741	arg1	coating					749:755	homemade polyvinyl alcohol (PVA) coating	716:755	homemade polyvinyl alcohol (PVA) coating	716:755	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	9	27	theme	developed	1460:1468	arg1	method					1486:1491	The developed CE-LIF analysis method	1456:1491	The developed CE-LIF analysis method	1456:1491	The developed CE-LIF analysis method was applied to the identification of N-glycans in IgG samples.
34809984	1	28	theme	Recombinant	98:108	arg1	biopharmaceuticals					118:135	Recombinant protein biopharmaceuticals	98:135	Recombinant protein biopharmaceuticals	98:135	Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape.
34809984	0	29	theme	N-Glycans	24:32	arg1	Cross-identification					0:19	Cross-identification	0:19	Cross-identification of N-Glycans by CE-LIF using two capillary coatings and three labeling dyes.	0:96	Cross-identification of N-Glycans by CE-LIF using two capillary coatings and three labeling dyes.
34809984	4	30	theme	labeling	587:594	arg1	dyes					596:599	three labeling dyes	581:599	three labeling dyes	581:599	To overcome this challenge in achieving accurate glycan identification, cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes was developed in this work.
34809984	7	31	theme	APTS	1113:1116	arg1	covariance					1099:1108	low covariance	1095:1108	low covariance of APTS and Turquoise™ labeling	1095:1140	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	1	32	theme	protein	110:116	arg1	biopharmaceuticals					118:135	Recombinant protein biopharmaceuticals	98:135	Recombinant protein biopharmaceuticals	98:135	Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape.
34809984	7	33	theme	low	1095:1097	arg1	covariance					1099:1108	low covariance	1095:1108	low covariance of APTS and Turquoise™ labeling	1095:1140	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	6	34	theme	capillary	885:893	arg1	coatings					895:902	the two capillary coatings	877:902	the two capillary coatings	877:902	Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary.
34809984	3	35	theme	structures	413:422	arg1	complexity					393:402	the complexity	389:402	the complexity of their structures	389:422	However, glycan analysis is challenging because of the complexity of their structures.
34809984	7	36	theme	labeling	1179:1186	arg1	mechanisms					1188:1197	hence these two labeling mechanisms	1163:1197	hence these two labeling mechanisms	1163:1197	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	4	37	theme	accurate	465:472	arg1	identification					481:494	accurate glycan identification	465:494	accurate glycan identification	465:494	To overcome this challenge in achieving accurate glycan identification, cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes was developed in this work.
34809984	8	38	dep	standards	1368:1376	arg1	IS					1379:1380	IS	1379:1380	IS	1379:1380	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	0	39	theme	capillary	54:62	arg1	coatings					64:71	two capillary coatings	50:71	two capillary coatings	50:71	Cross-identification of N-Glycans by CE-LIF using two capillary coatings and three labeling dyes.
34809984	9	40	theme	CE-LIF	1470:1475	arg1	method					1486:1491	The developed CE-LIF analysis method	1456:1491	The developed CE-LIF analysis method	1456:1491	The developed CE-LIF analysis method was applied to the identification of N-glycans in IgG samples.
34809984	2	41	theme	proteins	246:253	arg1	parameter					272:280	a key quality parameter	258:280	a key quality parameter as it can affect their safety, efficacy, and stability	258:335	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	2	41	theme	proteins	246:253	arg1	profile					229:235	The glycosylation profile	211:235	The glycosylation profile of these proteins	211:253	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	7	42	theme	fluorescent	1063:1073	arg1	dyes					1075:1078	three fluorescent dyes	1057:1078	three fluorescent dyes	1057:1078	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	8	43	theme	glycan	1322:1327	arg1	standards					1329:1337	all target glycan standards	1311:1337	all target glycan standards	1311:1337	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	8	44	theme	Superior	1259:1266	arg1	reproducibility					1268:1282	Superior reproducibility	1259:1282	Superior reproducibility with RSDs less than 1% for all target glycan standards	1259:1337	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	4	45	theme	capillary	558:566	arg1	coatings					568:575	two capillary coatings	554:575	two capillary coatings	554:575	To overcome this challenge in achieving accurate glycan identification, cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes was developed in this work.
34809984	8	46	theme	target	1315:1320	arg1	standards					1329:1337	all target glycan standards	1311:1337	all target glycan standards	1311:1337	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	5	47	theme	homemade	716:723	arg1	PVA					744:746	PVA	744:746	PVA	744:746	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	5	47	theme	homemade	716:723	arg1	alcohol					735:741	homemade polyvinyl alcohol	716:741	homemade polyvinyl alcohol (PVA) coating	716:755	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	9	48	theme	N-glycans	1530:1538	arg1	identification					1512:1525	the identification	1508:1525	the identification of N-glycans in IgG samples	1508:1553	The developed CE-LIF analysis method was applied to the identification of N-glycans in IgG samples.
34809984	5	49	theme	polyvinyl	725:733	arg1	PVA					744:746	PVA	744:746	PVA	744:746	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	5	49	theme	polyvinyl	725:733	arg1	alcohol					735:741	homemade polyvinyl alcohol	716:741	homemade polyvinyl alcohol (PVA) coating	716:755	This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans.
34809984	2	50	theme	glycosylation	215:227	arg1	parameter					272:280	a key quality parameter	258:280	a key quality parameter as it can affect their safety, efficacy, and stability	258:335	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	2	50	theme	glycosylation	215:227	arg1	profile					229:235	The glycosylation profile	211:235	The glycosylation profile of these proteins	211:253	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	8	51	theme	separation	1437:1446	arg1	buffer					1448:1453	the separation buffer	1433:1453	the separation buffer	1433:1453	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	8	52	with	reproducibility	1268:1282	arg1	%					1305:1305	RSDs less than 1%	1289:1305	RSDs less than 1%	1289:1305	Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer.
34809984	1	53	theme	significant	148:158	arg1	portion					160:166	a significant portion	146:166	a significant portion of the current drug development landscape	146:208	Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape.
34809984	7	54	theme	Turquoise™	1122:1131	arg1	labeling					1133:1140	Turquoise™ labeling	1122:1140	Turquoise™ labeling	1122:1140	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	2	55	theme	quality	264:270	arg1	profile					229:235	The glycosylation profile	211:235	The glycosylation profile of these proteins	211:253	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	2	55	theme	quality	264:270	arg1	parameter					272:280	a key quality parameter	258:280	a key quality parameter as it can affect their safety, efficacy, and stability	258:335	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	7	56	theme	cross-validation	1023:1038	arg1	performance					1008:1018	The performance	1004:1018	The performance of cross-validation by labeling with three fluorescent dyes	1004:1078	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
34809984	9	57	theme	IgG	1543:1545	arg1	samples					1547:1553	IgG samples	1543:1553	IgG samples	1543:1553	The developed CE-LIF analysis method was applied to the identification of N-glycans in IgG samples.
34809984	2	58	gly	glycosylation	215:227	arg1	proteins					246:253	these proteins	240:253	these proteins	240:253	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	4	59	theme	N-Glycans	521:529	arg1	cross-identification					497:516	cross-identification	497:516	cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes	497:599	To overcome this challenge in achieving accurate glycan identification, cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes was developed in this work.
34809984	2	60	theme	key	260:262	arg1	profile					229:235	The glycosylation profile	211:235	The glycosylation profile of these proteins	211:253	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	2	60	theme	key	260:262	arg1	parameter					272:280	a key quality parameter	258:280	a key quality parameter as it can affect their safety, efficacy, and stability	258:335	The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability.
34809984	7	61	theme	better	1208:1213	arg1	accuracy					1215:1222	better accuracy	1208:1222	better accuracy for the identification of glycans	1208:1256	The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans.
33270232	0	0	from	moieties	7:14	arg1	ubiquitin					41:49	Entamoeba histolytica ubiquitin	19:49	Entamoeba histolytica ubiquitin	19:49	Glycan moieties in Entamoeba histolytica ubiquitin are immunodominant.
33270232	4	1	theme	purified	441:448	arg1	rUb					462:464	purified recombinant rUb	441:464	purified recombinant rUb expressed by E. coli	441:485	Rabbits were immunized with purified EhUbiquitin or purified recombinant rUb expressed by E. coli.
33270232	2	2	from	characterization	216:231	arg1	histolytica					273:283	E. histolytica ubiquitin (EhUb)	270:300	E. histolytica ubiquitin (EhUb)	270:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	9	3	with	infection	1028:1036	arg1	histolytica					1053:1063	Entamoeba histolytica	1043:1063	Entamoeba histolytica	1043:1063	In humans, infection with Entamoeba histolytica induces strong IgG anti-Ub response.
33270232	10	4	theme	protein	1143:1149	arg1	moieties					1151:1158	the protein moieties	1139:1158	the protein moieties	1139:1158	The human antibodies recognize both, the protein moieties and the glycosylated structure.
33270232	2	5	from	profile	259:265	arg1	histolytica					273:283	E. histolytica ubiquitin (EhUb)	270:300	E. histolytica ubiquitin (EhUb)	270:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	8	6	theme	anti-Ub	949:955	arg1	antibodies					970:979	anti-Ub glycoprotein antibodies	949:979	anti-Ub glycoprotein antibodies	949:979	Conversely, anti-Ub glycoprotein antibodies are well maintained in circulation.
33270232	3	7	dep	immunogenicity	324:337	arg1	the					320:322	the	320:322	the	320:322	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	4	8	theme	recombinant	450:460	arg1	rUb					462:464	purified recombinant rUb	441:464	purified recombinant rUb expressed by E. coli	441:485	Rabbits were immunized with purified EhUbiquitin or purified recombinant rUb expressed by E. coli.
33270232	1	9	theme	ubiquitin-proteasome	75:94	arg1	system					96:101	The ubiquitin-proteasome system	71:101	The ubiquitin-proteasome system	71:101	The ubiquitin-proteasome system plays a central role performing several functions to maintain parasite homeostasis.
33270232	6	10	theme	protein	775:781	arg1	moiety					783:788	the protein moiety	771:788	the protein moiety of EhUbiquitin	771:803	Interestingly, immunized rabbits produced antibodies to both Ub glycoprotein and rUb; but antibodies against carbohydrates were immunodominant, rather than antibodies to the protein moiety of EhUbiquitin.
33270232	8	11	theme	glycoprotein	957:968	arg1	antibodies					970:979	anti-Ub glycoprotein antibodies	949:979	anti-Ub glycoprotein antibodies	949:979	Conversely, anti-Ub glycoprotein antibodies are well maintained in circulation.
33270232	2	12	dep	histolytica	273:283	arg1	ubiquitin					285:293	ubiquitin	285:293	E. histolytica ubiquitin (EhUb)	270:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	2	12	dep	histolytica	273:283	arg1	EhUb					296:299	EhUb	296:299	EhUb	296:299	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	9	13	theme	Entamoeba	1043:1051	arg1	histolytica					1053:1063	Entamoeba histolytica	1043:1063	Entamoeba histolytica	1043:1063	In humans, infection with Entamoeba histolytica induces strong IgG anti-Ub response.
33270232	6	14	theme	immunized	616:624	arg1	rabbits					626:632	immunized rabbits	616:632	immunized rabbits	616:632	Interestingly, immunized rabbits produced antibodies to both Ub glycoprotein and rUb; but antibodies against carbohydrates were immunodominant, rather than antibodies to the protein moiety of EhUbiquitin.
33270232	6	15	gly	glycoprotein	665:676	arg1	glycoprotein					665:676	Ub glycoprotein	662:676	Ub glycoprotein	662:676	Interestingly, immunized rabbits produced antibodies to both Ub glycoprotein and rUb; but antibodies against carbohydrates were immunodominant, rather than antibodies to the protein moiety of EhUbiquitin.
33270232	5	16	theme	protein	559:565	arg1	antigenicity					543:554	antigenicity	543:554	antigenicity	543:554	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	5	16	theme	protein	559:565	arg1	immunogenicity					524:537	immunogenicity	524:537	immunogenicity	524:537	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	13	17	theme	potential	1359:1367	arg1	targets					1369:1375	potential targets	1359:1375	potential targets for diagnose tests, drugs and vaccine	1359:1413	These data open the door to use carbohydrates as potential targets for diagnose tests, drugs and vaccine to prevent this parasitic disease.
33270232	0	18	theme	Glycan	0:5	arg1	moieties					7:14	Glycan moieties	0:14	Glycan moieties in Entamoeba histolytica ubiquitin	0:49	Glycan moieties in Entamoeba histolytica ubiquitin are immunodominant.
33270232	13	19	theme	diagnose	1381:1388	arg1	tests					1390:1394	diagnose tests	1381:1394	diagnose tests	1381:1394	These data open the door to use carbohydrates as potential targets for diagnose tests, drugs and vaccine to prevent this parasitic disease.
33270232	3	20	from	antigenicity	343:354	arg1	EhUbiquitin					376:386	EhUbiquitin	376:386	EhUbiquitin	376:386	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	0	21	theme	Entamoeba	19:27	arg1	ubiquitin					41:49	Entamoeba histolytica ubiquitin	19:49	Entamoeba histolytica ubiquitin	19:49	Glycan moieties in Entamoeba histolytica ubiquitin are immunodominant.
33270232	4	22	theme	purified	417:424	arg1	EhUbiquitin					426:436	purified EhUbiquitin	417:436	purified EhUbiquitin	417:436	Rabbits were immunized with purified EhUbiquitin or purified recombinant rUb expressed by E. coli.
33270232	1	23	theme	central	111:117	arg1	role					119:122	a central role	109:122	a central role performing several functions	109:151	The ubiquitin-proteasome system plays a central role performing several functions to maintain parasite homeostasis.
33270232	2	24	from	histolytica	273:283	arg1	characterization					216:231	the partial characterization	204:231	the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb)	204:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	11	25	theme	Entamoeba	1192:1200	arg1	ubiquitin					1214:1222	Entamoeba histolytica ubiquitin	1192:1222	Entamoeba histolytica ubiquitin	1192:1222	Entamoeba histolytica ubiquitin is immunogenic and antigenic.
33270232	9	26	theme	strong	1073:1078	arg1	response					1092:1099	strong IgG anti-Ub response	1073:1099	strong IgG anti-Ub response	1073:1099	In humans, infection with Entamoeba histolytica induces strong IgG anti-Ub response.
33270232	3	27	from	EhUbiquitin	376:386	arg1	antigenicity					343:354	antigenicity	343:354	antigenicity	343:354	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	3	27	from	EhUbiquitin	376:386	arg1	immunogenicity					324:337	immunogenicity	324:337	immunogenicity	324:337	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	11	28	theme	histolytica	1202:1212	arg1	ubiquitin					1214:1222	Entamoeba histolytica ubiquitin	1192:1222	Entamoeba histolytica ubiquitin	1192:1222	Entamoeba histolytica ubiquitin is immunogenic and antigenic.
33270232	9	29	theme	IgG	1080:1082	arg1	response					1092:1099	strong IgG anti-Ub response	1073:1099	strong IgG anti-Ub response	1073:1099	In humans, infection with Entamoeba histolytica induces strong IgG anti-Ub response.
33270232	2	30	theme	E.	270:271	arg1	histolytica					273:283	E. histolytica ubiquitin (EhUb)	270:300	E. histolytica ubiquitin (EhUb)	270:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	2	31	link	N-linked	236:243	arg1	glycosylation					245:257	N-linked glycosylation	236:257	N-linked glycosylation profile in E. histolytica ubiquitin (EhUb)	236:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	0	32	theme	histolytica	29:39	arg1	ubiquitin					41:49	Entamoeba histolytica ubiquitin	19:49	Entamoeba histolytica ubiquitin	19:49	Glycan moieties in Entamoeba histolytica ubiquitin are immunodominant.
33270232	8	33	gly	glycoprotein	957:968	arg1	glycoprotein					957:968	anti-Ub glycoprotein antibodies	949:979	anti-Ub glycoprotein antibodies	949:979	Conversely, anti-Ub glycoprotein antibodies are well maintained in circulation.
33270232	10	34	theme	human	1106:1110	arg1	antibodies					1112:1121	The human antibodies	1102:1121	The human antibodies	1102:1121	The human antibodies recognize both, the protein moieties and the glycosylated structure.
33270232	6	35	theme	Ub	662:663	arg1	glycoprotein					665:676	Ub glycoprotein	662:676	Ub glycoprotein	662:676	Interestingly, immunized rabbits produced antibodies to both Ub glycoprotein and rUb; but antibodies against carbohydrates were immunodominant, rather than antibodies to the protein moiety of EhUbiquitin.
33270232	7	36	theme	protein	850:856	arg1	moiety					858:863	protein moiety	850:863	protein moiety	850:863	In addition, we observed that antibodies to protein moiety are not conserved in serum unless antigen is continually administrated.
33270232	2	37	theme	profile	259:265	arg1	characterization					216:231	the partial characterization	204:231	the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb)	204:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	5	38	dep	protein	559:565	arg1	portion					567:573	portion	567:573	portion	567:573	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	5	38	dep	protein	559:565	arg1	moiety					593:598	moiety	593:598	moiety	593:598	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	2	39	theme	N-linked	236:243	arg1	glycosylation					245:257	N-linked glycosylation	236:257	N-linked glycosylation profile in E. histolytica ubiquitin (EhUb)	236:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	2	40	theme	glycosylation	245:257	arg1	profile					259:265	N-linked glycosylation profile	236:265	N-linked glycosylation profile in E. histolytica ubiquitin (EhUb)	236:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	1	41	theme	several	135:141	arg1	functions					143:151	several functions	135:151	several functions	135:151	The ubiquitin-proteasome system plays a central role performing several functions to maintain parasite homeostasis.
33270232	12	42	theme	glycan	1258:1263	arg1	immunodominant					1278:1291	immunodominant	1278:1291	immunodominant	1278:1291	The glycan moieties are immunodominant and induces IgG.
33270232	12	42	theme	glycan	1258:1263	arg1	moieties					1265:1272	The glycan moieties	1254:1272	The glycan moieties	1254:1272	The glycan moieties are immunodominant and induces IgG.
33270232	5	43	theme	Western	494:500	arg1	Blot					502:505	Western Blot	494:505	Western Blot	494:505	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	13	44	theme	parasitic	1431:1439	arg1	disease					1441:1447	this parasitic disease	1426:1447	this parasitic disease	1426:1447	These data open the door to use carbohydrates as potential targets for diagnose tests, drugs and vaccine to prevent this parasitic disease.
33270232	3	45	from	carbohydrates	359:371	arg1	EhUbiquitin					376:386	EhUbiquitin	376:386	EhUbiquitin	376:386	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	6	46	theme	EhUbiquitin	793:803	arg1	moiety					783:788	the protein moiety	771:788	the protein moiety of EhUbiquitin	771:803	Interestingly, immunized rabbits produced antibodies to both Ub glycoprotein and rUb; but antibodies against carbohydrates were immunodominant, rather than antibodies to the protein moiety of EhUbiquitin.
33270232	10	47	gly	glycosylated	1168:1179	arg1	structure					1181:1189	the glycosylated structure	1164:1189	the glycosylated structure	1164:1189	The human antibodies recognize both, the protein moieties and the glycosylated structure.
33270232	9	48	theme	anti-Ub	1084:1090	arg1	response					1092:1099	strong IgG anti-Ub response	1073:1099	strong IgG anti-Ub response	1073:1099	In humans, infection with Entamoeba histolytica induces strong IgG anti-Ub response.
33270232	3	49	theme	carbohydrates	359:371	arg1	antigenicity					343:354	antigenicity	343:354	antigenicity	343:354	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	3	49	theme	carbohydrates	359:371	arg1	immunogenicity					324:337	immunogenicity	324:337	immunogenicity	324:337	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	2	50	theme	partial	208:214	arg1	characterization					216:231	the partial characterization	204:231	the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb)	204:300	We have reported the partial characterization of N-linked glycosylation profile in E. histolytica ubiquitin (EhUb).
33270232	5	51	dep	immunogenicity	524:537	arg1	the					520:522	the	520:522	the	520:522	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	3	52	from	immunogenicity	324:337	arg1	EhUbiquitin					376:386	EhUbiquitin	376:386	EhUbiquitin	376:386	Here we examined the immunogenicity and antigenicity of carbohydrates in EhUbiquitin.
33270232	10	53	theme	glycosylated	1168:1179	arg1	structure					1181:1189	the glycosylated structure	1164:1189	the glycosylated structure	1164:1189	The human antibodies recognize both, the protein moieties and the glycosylated structure.
33270232	5	54	theme	carbohydrates	579:591	arg1	antigenicity					543:554	antigenicity	543:554	antigenicity	543:554	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	5	54	theme	carbohydrates	579:591	arg1	immunogenicity					524:537	immunogenicity	524:537	immunogenicity	524:537	Using Western Blot, we explored the immunogenicity and antigenicity of protein portion and carbohydrates moiety.
33270232	1	55	theme	parasite	165:172	arg1	homeostasis					174:184	parasite homeostasis	165:184	parasite homeostasis	165:184	The ubiquitin-proteasome system plays a central role performing several functions to maintain parasite homeostasis.
34644263	10	0	theme	tumor	1423:1427	arg1	cells					1429:1433	Tn+ tumor cells	1419:1433	Tn+ tumor cells	1419:1433	Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn+ tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.
34644263	5	1	theme	LS174T-Tn-	817:826	arg1	cells					828:832	LS174T-Tn- cells	817:832	LS174T-Tn- cells	817:832	Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn- cells.
34644263	8	2	theme	LS174T-Tn+	1111:1120	arg1	cells					1122:1126	Jurkat T and LS174T-Tn+ cells	1098:1126	cells	1122:1126	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	7	3	theme	T	1010:1010	arg1	cells					1012:1016	Jurkat T cells	1003:1016	Jurkat T cells	1003:1016	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	2	4	with	proliferation	298:310	arg1	Cosmc					383:387	mutant Cosmc	376:387	mutant Cosmc	376:387	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	5	5	theme	structural	764:773	arg1	types					775:779	their structural types	758:779	their structural types	758:779	Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn- cells.
34644263	10	6	theme	Tn+	1419:1421	arg1	cells					1429:1433	Tn+ tumor cells	1419:1433	Tn+ tumor cells	1419:1433	Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn+ tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.
34644263	2	7	theme	Jurkat	340:345	arg1	T					347:347	Jurkat T and LS174T-Tn+ cells	340:368	T	347:347	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	9	8	dep	composition	1163:1173	arg1	the					1159:1161	the	1159:1161	the	1159:1161	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	10	9	theme	Cosmc	1349:1353	arg1	transfection					1355:1366	Cosmc transfection	1349:1366	Cosmc transfection	1349:1366	Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn+ tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.
34644263	3	10	theme	3-derived	510:518	arg1	O-glycans					520:528	3-derived O-glycans	510:528	3-derived O-glycans	510:528	Core 1-, 2-, and 3-derived O-glycans were absent in Tn+ cells.
34644263	2	11	dep	cells	333:337	arg1	T					347:347	Jurkat T and LS174T-Tn+ cells	340:368	T	347:347	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	2	11	dep	cells	333:337	arg1	cells					364:368	Jurkat T and LS174T-Tn+ cells	340:368	cells	364:368	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	2	12	with	migration	316:324	arg1	Cosmc					383:387	mutant Cosmc	376:387	mutant Cosmc	376:387	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	5	13	theme	transfected	724:734	arg1	cells					747:751	transfected LS174T-Tn+ cells	724:751	transfected LS174T-Tn+ cells	724:751	Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn- cells.
34644263	9	14	theme	cell	1266:1269	arg1	behavior					1281:1288	cell malignant behavior	1266:1288	cell malignant behavior	1266:1288	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	8	15	theme	core	1070:1073	arg1	O-glycans					1085:1093	core 3-derived O-glycans	1070:1093	core 3-derived O-glycans	1070:1093	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	3	16	link	3-derived	510:518	arg1	O-glycans					520:528	3-derived O-glycans	510:528	3-derived O-glycans	510:528	Core 1-, 2-, and 3-derived O-glycans were absent in Tn+ cells.
34644263	6	17	theme	LS174T-Tn-	881:890	arg1	cells					892:896	LS174T-Tn- cells	881:896	LS174T-Tn- cells	881:896	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	8	18	theme	Cosmc	1019:1023	arg1	transfection					1025:1036	Cosmc transfection	1019:1036	Cosmc transfection	1019:1036	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	4	19	theme	core	598:601	arg1	O-glycans					613:621	normal extended core 1-derived O-glycans	582:621	normal extended core 1-derived O-glycans	582:621	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
34644263	10	20	theme	O-glycans	1530:1538	arg1	modification					1514:1525	modification	1514:1525	modification of O-glycans	1514:1538	Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn+ tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.
34644263	2	21	theme	mutant	376:381	arg1	Cosmc					383:387	mutant Cosmc	376:387	mutant Cosmc	376:387	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	8	22	from	O-glycans	1085:1093	arg1	T					1105:1105	Jurkat T and LS174T-Tn+ cells	1098:1126	T	1105:1105	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	8	22	from	O-glycans	1085:1093	arg1	cells					1122:1126	Jurkat T and LS174T-Tn+ cells	1098:1126	cells	1122:1126	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	6	23	theme	3-derived	840:848	arg1	O-glycans					850:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	5	24	theme	LS174T-Tn+	736:745	arg1	cells					747:751	transfected LS174T-Tn+ cells	724:751	transfected LS174T-Tn+ cells	724:751	Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn- cells.
34644263	10	25	theme	malignant	1397:1405	arg1	behavior					1407:1414	the malignant behavior	1393:1414	the malignant behavior of Tn+ tumor cells	1393:1433	Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn+ tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.
34644263	9	26	theme	malignant	1271:1279	arg1	behavior					1281:1288	cell malignant behavior	1266:1288	cell malignant behavior	1266:1288	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	0	27	theme	Cosmc	0:4	arg1	transfection					6:17	Cosmc transfection	0:17	Cosmc transfection	0:17	Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.
34644263	10	28	theme	cells	1429:1433	arg1	behavior					1407:1414	the malignant behavior	1393:1414	the malignant behavior of Tn+ tumor cells	1393:1433	Thus, Cosmc transfection may effectively decrease the malignant behavior of Tn+ tumor cells and enhance their sensitivity to apoptosis when induced by Apo2L/TRAIL through modification of O-glycans.
34644263	7	29	theme	C3GnT	915:919	arg1	lower					945:949	lower	945:949	lower	945:949	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	7	29	theme	C3GnT	915:919	arg1	activity					903:910	The activity	899:910	The activity of C3GnT in LS174T-Tn+ cells	899:939	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	3	30	theme	Tn+	545:547	arg1	cells					549:553	Tn+ cells	545:553	Tn+ cells	545:553	Core 1-, 2-, and 3-derived O-glycans were absent in Tn+ cells.
34644263	3	31	from	cells	549:553	arg1	absent					535:540	absent	535:540	absent	535:540	Core 1-, 2-, and 3-derived O-glycans were absent in Tn+ cells.
34644263	1	32	theme	abnormal	191:198	arg1	O-glycosylation					200:214	abnormal O-glycosylation	191:214	abnormal O-glycosylation	191:214	Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression.
34644263	0	33	theme	malignant	29:37	arg1	behavior					39:46	malignant behavior	29:46	malignant behavior of Tn+ cells	29:59	Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.
34644263	5	34	theme	Core	687:690	arg1	O-glycans					702:710	Core 2-derived O-glycans	687:710	Core 2-derived O-glycans	687:710	Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn- cells.
34644263	7	35	from	activity	903:910	arg1	cells					935:939	LS174T-Tn+ cells	924:939	LS174T-Tn+ cells	924:939	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	8	36	link	3-derived	1075:1083	arg1	O-glycans					1085:1093	core 3-derived O-glycans	1070:1093	core 3-derived O-glycans	1070:1093	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	2	37	theme	transfected	405:415	arg1	Cosmc					417:421	transfected Cosmc	405:421	transfected Cosmc	405:421	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	9	38	theme	various	1223:1229	arg1	cells					1235:1239	various Tn+ cells	1223:1239	various Tn+ cells	1223:1239	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	5	39	link	2-derived	692:700	arg1	O-glycans					702:710	Core 2-derived O-glycans	687:710	Core 2-derived O-glycans	687:710	Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn- cells.
34644263	5	40	theme	2-derived	692:700	arg1	O-glycans					702:710	Core 2-derived O-glycans	687:710	Core 2-derived O-glycans	687:710	Core 2-derived O-glycans appeared in transfected LS174T-Tn+ cells, and their structural types and levels were lower than those in LS174T-Tn- cells.
34644263	9	41	theme	O-glycans	1192:1200	arg1	structure					1179:1187	structure	1179:1187	structure	1179:1187	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	9	41	theme	O-glycans	1192:1200	arg1	composition					1163:1173	composition	1163:1173	composition	1163:1173	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	1	42	theme	Cosmc	165:169	arg1	mutations					171:179	Cosmc mutations	165:179	Cosmc mutations	165:179	Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression.
34644263	4	43	theme	T-synthase	666:675	arg1	activity					677:684	increased T-synthase activity	656:684	increased T-synthase activity	656:684	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
34644263	6	44	link	3-derived	840:848	arg1	O-glycans					850:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	8	45	from	activity	1058:1065	arg1	T					1105:1105	Jurkat T and LS174T-Tn+ cells	1098:1126	T	1105:1105	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	8	45	from	activity	1058:1065	arg1	cells					1122:1126	Jurkat T and LS174T-Tn+ cells	1098:1126	cells	1122:1126	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	9	46	theme	apoptotic	1324:1332	arg1	stimuli					1334:1340	apoptotic stimuli	1324:1340	apoptotic stimuli	1324:1340	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	8	47	theme	C3GnT	1052:1056	arg1	activity					1058:1065	C3GnT activity	1052:1065	C3GnT activity	1052:1065	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	6	48	from	present	865:871	arg1	cells					892:896	LS174T-Tn- cells	881:896	LS174T-Tn- cells	881:896	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	7	49	from	absent	993:998	arg1	cells					1012:1016	Jurkat T cells	1003:1016	Jurkat T cells	1003:1016	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	0	50	theme	cells	55:59	arg1	behavior					39:46	malignant behavior	29:46	malignant behavior of Tn+ cells	29:59	Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.
34644263	0	51	theme	structure	154:162	arg1	alteration					131:140	alteration	131:140	alteration of O-glycan structure	131:162	Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.
34644263	6	52	located	present	865:871	arg2	O-glycans					850:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	6	52	located	present	865:871	arg1	cells					892:896	LS174T-Tn- cells	881:896	LS174T-Tn- cells	881:896	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	0	53	theme	Tn+	51:53	arg1	cells					55:59	Tn+ cells	51:59	Tn+ cells	51:59	Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.
34644263	7	54	theme	LS174T-Tn-	964:973	arg1	cells					975:979	LS174T-Tn- cells	964:979	LS174T-Tn- cells	964:979	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	0	55	theme	O-glycan	145:152	arg1	structure					154:162	O-glycan structure	145:162	O-glycan structure	145:162	Cosmc transfection decreases malignant behavior of Tn+ cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure.
34644263	6	56	theme	Core	835:838	arg1	O-glycans					850:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	9	57	theme	Tn+	1231:1233	arg1	cells					1235:1239	various Tn+ cells	1223:1239	various Tn+ cells	1223:1239	The results demonstrated that the composition and structure of O-glycans were different among various Tn+ cells, which not only affected cell malignant behavior but also modulated sensitivity to apoptotic stimuli.
34644263	2	58	theme	cells	333:337	arg1	proliferation					298:310	proliferation	298:310	proliferation	298:310	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	2	58	theme	cells	333:337	arg1	migration					316:324	migration	316:324	migration	316:324	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	7	59	theme	LS174T-Tn+	924:933	arg1	cells					935:939	LS174T-Tn+ cells	924:939	LS174T-Tn+ cells	924:939	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	6	60	from	cells	892:896	arg1	present					865:871	present	865:871	present	865:871	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	8	61	theme	3-derived	1075:1083	arg1	O-glycans					1085:1093	core 3-derived O-glycans	1070:1093	core 3-derived O-glycans	1070:1093	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	2	62	theme	Tn+	329:331	arg1	cells					333:337	Tn+ cells	329:337	Tn+ cells (Jurkat T and LS174T-Tn+ cells)	329:369	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	3	63	from	absent	535:540	arg1	cells					549:553	Tn+ cells	545:553	Tn+ cells	545:553	Core 1-, 2-, and 3-derived O-glycans were absent in Tn+ cells.
34644263	1	64	theme	Tn	230:231	arg1	expression					241:250	Tn antigen expression	230:250	Tn antigen expression	230:250	Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression.
34644263	7	65	theme	Jurkat	1003:1008	arg1	cells					1012:1016	Jurkat T cells	1003:1016	Jurkat T cells	1003:1016	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	2	66	theme	current	260:266	arg1	study					268:272	the current study	256:272	the current study	256:272	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	6	67	attach	present	865:871	arg2	O-glycans					850:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans	835:858	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	6	67	attach	present	865:871	arg1	cells					892:896	LS174T-Tn- cells	881:896	LS174T-Tn- cells	881:896	Core 3-derived O-glycans were present only in LS174T-Tn- cells.
34644263	1	68	theme	antigen	233:239	arg1	expression					241:250	Tn antigen expression	230:250	Tn antigen expression	230:250	Cosmc mutations may cause abnormal O-glycosylation and result in Tn antigen expression.
34644263	8	69	theme	Jurkat	1098:1103	arg1	T					1105:1105	Jurkat T and LS174T-Tn+ cells	1098:1126	T	1105:1105	Cosmc transfection did not alter C3GnT activity or core 3-derived O-glycans in Jurkat T and LS174T-Tn+ cells.
34644263	4	70	link	1-derived	603:611	arg1	O-glycans					613:621	normal extended core 1-derived O-glycans	582:621	normal extended core 1-derived O-glycans	582:621	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
34644263	4	71	theme	1-derived	603:611	arg1	O-glycans					613:621	normal extended core 1-derived O-glycans	582:621	normal extended core 1-derived O-glycans	582:621	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
34644263	2	72	theme	LS174T-Tn+	353:362	arg1	cells					364:368	Jurkat T and LS174T-Tn+ cells	340:368	cells	364:368	In the current study, it was discovered that proliferation and migration of Tn+ cells (Jurkat T and LS174T-Tn+ cells) with mutant Cosmc decreased after transfected Cosmc, and their sensitivity to apoptosis induced by Apo2L/TRAIL increased.
34644263	4	73	theme	extended	589:596	arg1	O-glycans					613:621	normal extended core 1-derived O-glycans	582:621	normal extended core 1-derived O-glycans	582:621	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
34644263	4	74	theme	Cosmc	562:566	arg1	transfection					568:579	Cosmc transfection	562:579	Cosmc transfection	562:579	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
34644263	7	75	from	cells	1012:1016	arg1	absent					993:998	absent	993:998	absent	993:998	The activity of C3GnT in LS174T-Tn+ cells was lower than that in LS174T-Tn- cells, and it was absent in Jurkat T cells.
34644263	4	76	theme	increased	656:664	arg1	activity					677:684	increased T-synthase activity	656:684	increased T-synthase activity	656:684	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
34644263	4	77	theme	normal	582:587	arg1	O-glycans					613:621	normal extended core 1-derived O-glycans	582:621	normal extended core 1-derived O-glycans	582:621	After Cosmc transfection, normal extended core 1-derived O-glycans appeared and were accompanied by increased T-synthase activity.
32298669	10	0	theme	glycans	1599:1605	arg1	increase					1569:1576	increase	1569:1576	increase of high mannose type glycans what was confirmed also by MALDI-MS	1569:1641	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	11	1	theme	lectin-based	1699:1710	arg1	microarray					1720:1729	lectin-based protein microarray	1699:1729	lectin-based protein microarray	1699:1729	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	10	2	theme	lectin-based	1451:1462	arg1	analysis					1475:1482	lectin-based microarray analysis	1451:1482	lectin-based microarray analysis	1451:1482	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	5	3	from	evaluation	784:793	arg1	glycosylation					809:821	glycosylation	809:821	glycosylation	809:821	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	12	4	theme	glycosylation	2128:2140	arg1	screening					2100:2108	screening	2100:2108	screening	2100:2108	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	12	4	theme	glycosylation	2128:2140	arg1	determination					2085:2097	determination	2085:2097	determination	2085:2097	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	12	4	theme	glycosylation	2128:2140	arg1	evaluation					2114:2123	evaluation	2114:2123	evaluation	2114:2123	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	5	5	from	specificity	768:778	arg1	glycosylation					809:821	glycosylation	809:821	glycosylation	809:821	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	12	6	theme	therapeutic	2145:2155	arg1	proteins					2157:2164	therapeutic proteins	2145:2164	therapeutic proteins	2145:2164	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	8	7	theme	different	1235:1243	arg1	conditions					1245:1254	different conditions	1235:1254	different conditions	1235:1254	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	8	8	theme	IgA1	1056:1059	arg1	antibodies					1061:1070	Dimeric IgA1 antibodies	1048:1070	Dimeric IgA1 antibodies	1048:1070	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	4	9	from	structures	536:545	arg1	investigation					501:513	the investigation	497:513	the investigation of changes in glycan structures	497:545	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	2	10	theme	glycan	287:292	arg1	composition					294:304	glycan composition	287:304	glycan composition	287:304	The determination of glycan composition is highly important regarding their development and production.
32298669	4	11	from	investigation	501:513	arg1	structures					536:545	glycan structures	529:545	glycan structures	529:545	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	1	12	gly	glycoproteins	163:175	arg1	glycoproteins					163:175	therapeutic glycoproteins	151:175	therapeutic glycoproteins	151:175	Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity.
32298669	5	13	theme	lectin-based	630:641	arg1	analysis					654:661	lectin-based microarray analysis	630:661	lectin-based microarray analysis	630:661	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	8	14	from	IgA1/2G9	1106:1113	arg1	medium					1128:1133	the basal medium	1118:1133	the basal medium	1118:1133	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	11	15	with	supplementation	1874:1888	arg1	mannose					1922:1928	mannose	1922:1928	mannose	1922:1928	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	11	15	with	supplementation	1874:1888	arg1	feeding					1909:1915	feeding	1909:1915	feeding	1909:1915	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	11	15	with	supplementation	1874:1888	arg1	glutamine					1895:1903	glutamine	1895:1903	glutamine	1895:1903	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	1	16	theme	therapeutic	151:161	arg1	glycoproteins					163:175	therapeutic glycoproteins	151:175	therapeutic glycoproteins	151:175	Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity.
32298669	9	17	theme	levels	1339:1344	arg1	Decrease					1319:1326	Decrease	1319:1326	Decrease of lactate levels	1319:1344	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	12	18	theme	described	2022:2030	arg1	approach					2043:2050	the described analytical approach	2018:2050	the described analytical approach	2018:2050	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	0	19	from	Influence	0:8	arg1	glycosylation					62:74	recombinant monoclonal IgA1 glycosylation	34:74	recombinant monoclonal IgA1 glycosylation	34:74	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	5	20	theme	changes	798:804	arg1	specificity					768:778	specificity	768:778	specificity	768:778	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	5	20	theme	changes	798:804	arg1	evaluation					784:793	evaluation	784:793	evaluation	784:793	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	8	21	theme	cell	1096:1099	arg1	IgA1/2G9					1106:1113	stable cell line IgA1/2G9	1089:1113	stable cell line IgA1/2G9 on the basal medium	1089:1133	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	10	22	with	shift	1503:1507	arg1	glucose					1554:1560	glucose	1554:1560	glucose	1554:1560	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	3	23	theme	analytical	403:412	arg1	techniques					414:423	analytical techniques	403:423	analytical techniques enabling rapid and reliable glycoprofiling of therapeutic proteins	403:490	Therefore, there is a demand for analytical techniques enabling rapid and reliable glycoprofiling of therapeutic proteins.
32298669	9	24	theme	succinic	1387:1394	arg1	asparagine					1402:1411	asparagine	1402:1411	asparagine	1402:1411	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	9	24	theme	succinic	1387:1394	arg1	acid					1396:1399	succinic acid	1387:1399	succinic acid	1387:1399	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	6	25	used	used	900:903	arg2	MALDI-MS					887:894	MALDI-MS	887:894	MALDI-MS	887:894	MALDI-MS was used for N-glycan analysis of IgA1 samples.
32298669	7	26	from	agents	978:983	arg1	defense					988:994	defense	988:994	defense against viruses that use sialic acid as a receptor	988:1045	IgAs are effective as therapeutic agents in defense against viruses that use sialic acid as a receptor.
32298669	0	27	theme	media	13:17	arg1	composition					19:29	media composition	13:29	media composition	13:29	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	12	28	theme	determined	1963:1972	arg1	changes					1974:1980	determined changes	1963:1980	determined changes	1963:1980	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	6	29	theme	samples	935:941	arg1	analysis					918:925	N-glycan analysis	909:925	N-glycan analysis of IgA1 samples	909:941	MALDI-MS was used for N-glycan analysis of IgA1 samples.
32298669	8	30	theme	different	1138:1146	arg1	feeding					1190:1196	feeding	1190:1196	feeding	1190:1196	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	8	30	theme	different	1138:1146	arg1	conditions					1148:1157	different conditions	1138:1157	different conditions (different supplementation and feeding)	1138:1197	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	8	30	theme	different	1138:1146	arg1	supplementation					1170:1184	different supplementation	1160:1184	different supplementation	1160:1184	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	3	31	theme	therapeutic	471:481	arg1	proteins					483:490	therapeutic proteins	471:490	therapeutic proteins	471:490	Therefore, there is a demand for analytical techniques enabling rapid and reliable glycoprofiling of therapeutic proteins.
32298669	10	32	theme	type	1594:1597	arg1	glycans					1599:1605	high mannose type glycans	1581:1605	high mannose type glycans what was confirmed also by MALDI-MS	1581:1641	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	0	33	theme	monoclonal	46:55	arg1	glycosylation					62:74	recombinant monoclonal IgA1 glycosylation	34:74	recombinant monoclonal IgA1 glycosylation	34:74	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	8	34	from	effect	1225:1230	arg1	production					1267:1276	lactate production	1259:1276	lactate production	1259:1276	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	10	35	theme	high	1581:1584	arg1	glycans					1599:1605	high mannose type glycans	1581:1605	high mannose type glycans what was confirmed also by MALDI-MS	1581:1641	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	11	36	theme	other	1650:1654	arg1	changes					1656:1662	other changes	1650:1662	other changes in IgA glycosylation determined by lectin-based protein microarray	1650:1729	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	12	37	theme	mechanism	1950:1958	arg1	elucidation					1935:1945	The elucidation	1931:1945	The elucidation of mechanism of determined changes	1931:1980	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	11	38	theme	succinic	1801:1808	arg1	acid					1810:1813	succinic acid	1801:1813	succinic acid	1801:1813	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	12	39	gly	glycosylation	2128:2140	arg1	proteins					2157:2164	therapeutic proteins	2145:2164	therapeutic proteins	2145:2164	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	7	40	theme	therapeutic	966:976	arg1	agents					978:983	therapeutic agents	966:983	therapeutic agents in defense against viruses that use sialic acid as a receptor	966:1045	IgAs are effective as therapeutic agents in defense against viruses that use sialic acid as a receptor.
32298669	12	41	theme	proteins	2157:2164	arg1	glycosylation					2128:2140	glycosylation	2128:2140	glycosylation of therapeutic proteins	2128:2164	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	12	42	theme	analytical	2032:2041	arg1	approach					2043:2050	the described analytical approach	2018:2050	the described analytical approach	2018:2050	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	11	43	theme	protein	1712:1718	arg1	microarray					1720:1729	lectin-based protein microarray	1699:1729	lectin-based protein microarray	1699:1729	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	8	44	theme	Dimeric	1048:1054	arg1	antibodies					1061:1070	Dimeric IgA1 antibodies	1048:1070	Dimeric IgA1 antibodies	1048:1070	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	5	45	with	samples	865:871	arg1	lectins					878:884	lectins	878:884	lectins	878:884	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	1	46	theme	physico-chemical	205:220	arg1	immunogenicity					250:263	immunogenicity	250:263	immunogenicity	250:263	Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity.
32298669	1	46	theme	physico-chemical	205:220	arg1	bioactivity					234:244	bioactivity	234:244	bioactivity	234:244	Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity.
32298669	1	46	theme	physico-chemical	205:220	arg1	properties					222:231	their physico-chemical properties	199:231	their physico-chemical properties	199:231	Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity.
32298669	5	47	theme	samples	865:871	arg1	reactivity					851:860	reactivity	851:860	reactivity of samples with lectins	851:884	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	5	48	theme	microarray	703:712	arg1	slide					714:718	the microarray slide	699:718	the microarray slide	699:718	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	6	49	theme	N-glycan	909:916	arg1	analysis					918:925	N-glycan analysis	909:925	N-glycan analysis of IgA1 samples	909:941	MALDI-MS was used for N-glycan analysis of IgA1 samples.
32298669	8	50	theme	IgA	1301:1303	arg1	productivity					1305:1316	IgA productivity	1301:1316	IgA productivity	1301:1316	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	5	51	theme	various	760:766	arg1	specificity					768:778	specificity	768:778	specificity	768:778	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	10	52	theme	microarray	1464:1473	arg1	analysis					1475:1482	lectin-based microarray analysis	1451:1482	lectin-based microarray analysis	1451:1482	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	8	53	theme	conditions	1245:1254	arg1	effect					1225:1230	the effect	1221:1230	the effect of different conditions on lactate production, which correlates with IgA productivity	1221:1316	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	10	54	from	glutamine	1514:1522	arg1	shift					1503:1507	the metabolic shift	1489:1507	the metabolic shift from glutamine to asparagine or feeding with glucose	1489:1560	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	4	55	theme	glycan	529:534	arg1	structures					536:545	glycan structures	529:545	glycan structures	529:545	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	8	56	dep	conditions	1148:1157	arg1	feeding					1190:1196	feeding	1190:1196	feeding	1190:1196	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	8	56	dep	conditions	1148:1157	arg1	conditions					1148:1157	different conditions	1138:1157	different conditions (different supplementation and feeding)	1138:1197	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	8	56	dep	conditions	1148:1157	arg1	supplementation					1170:1184	different supplementation	1160:1184	different supplementation	1160:1184	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	5	57	from	glycosylation	809:821	arg1	specificity					768:778	specificity	768:778	specificity	768:778	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	5	57	from	glycosylation	809:821	arg1	evaluation					784:793	evaluation	784:793	evaluation	784:793	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	2	58	theme	composition	294:304	arg1	determination					270:282	The determination	266:282	The determination of glycan composition	266:304	The determination of glycan composition is highly important regarding their development and production.
32298669	2	58	theme	composition	294:304	arg1	important					316:324	important	316:324	important	316:324	The determination of glycan composition is highly important regarding their development and production.
32298669	11	59	with	supplementation	1780:1794	arg1	increase					1819:1826	increase	1819:1826	increase of both sialylation and galactosylation	1819:1866	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	11	59	with	supplementation	1780:1794	arg1	acid					1810:1813	succinic acid	1801:1813	succinic acid	1801:1813	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	11	60	from	changes	1656:1662	arg1	glycosylation					1671:1683	IgA glycosylation	1667:1683	IgA glycosylation determined by lectin-based protein microarray	1667:1729	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	8	61	theme	lactate	1259:1265	arg1	production					1267:1276	lactate production	1259:1276	lactate production	1259:1276	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	4	62	from	changes	518:524	arg1	structures					536:545	glycan structures	529:545	glycan structures	529:545	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	5	63	from	changes	798:804	arg1	glycosylation					809:821	glycosylation	809:821	glycosylation	809:821	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	4	64	theme	lectin-based	580:591	arg1	microarray					601:610	lectin-based protein microarray	580:610	lectin-based protein microarray	580:610	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	4	64	theme	lectin-based	580:591	arg1	platforms					569:577	two platforms	565:577	two platforms: lectin-based protein microarray, and MALDI-MS	565:624	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	1	65	gly	Glycosylation	134:146	arg1	glycoproteins					163:175	therapeutic glycoproteins	151:175	therapeutic glycoproteins	151:175	Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity.
32298669	5	66	theme	lectins	747:753	arg1	lectins					747:753	lectins	747:753	lectins with various specificity and evaluation of changes in glycosylation	747:821	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	5	66	theme	lectins	747:753	arg1	set					740:742	the set	736:742	the set of lectins with various specificity and evaluation of changes in glycosylation	736:821	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	5	67	from	differences	836:846	arg1	reactivity					851:860	reactivity	851:860	reactivity of samples with lectins	851:884	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	5	68	theme	microarray	643:652	arg1	analysis					654:661	lectin-based microarray analysis	630:661	lectin-based microarray analysis	630:661	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	4	69	theme	changes	518:524	arg1	investigation					501:513	the investigation	497:513	the investigation of changes in glycan structures	497:545	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	9	70	with	supplementation	1366:1380	arg1	feeding					1430:1436	mannose feeding	1422:1436	mannose feeding	1422:1436	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	9	70	with	supplementation	1366:1380	arg1	asparagine					1402:1411	asparagine	1402:1411	asparagine	1402:1411	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	9	70	with	supplementation	1366:1380	arg1	acid					1396:1399	succinic acid	1387:1399	succinic acid	1387:1399	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	11	71	theme	sialylation	1836:1846	arg1	increase					1819:1826	increase	1819:1826	increase of both sialylation and galactosylation	1819:1866	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	11	71	theme	sialylation	1836:1846	arg1	acid					1810:1813	succinic acid	1801:1813	succinic acid	1801:1813	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	9	72	theme	lactate	1331:1337	arg1	levels					1339:1344	lactate levels	1331:1344	lactate levels	1331:1344	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	1	73	theme	glycoproteins	163:175	arg1	Glycosylation					134:146	Glycosylation	134:146	Glycosylation of therapeutic glycoproteins	134:175	Glycosylation of therapeutic glycoproteins significantly affects their physico-chemical properties, bioactivity and immunogenicity.
32298669	0	74	theme	protein	101:107	arg1	microarray					109:118	lectin-based protein microarray	88:118	lectin-based protein microarray	88:118	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	0	75	theme	lectin-based	88:99	arg1	microarray					109:118	lectin-based protein microarray	88:118	lectin-based protein microarray	88:118	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	8	76	theme	stable	1089:1094	arg1	IgA1/2G9					1106:1113	stable cell line IgA1/2G9	1089:1113	stable cell line IgA1/2G9 on the basal medium	1089:1133	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	4	77	theme	protein	593:599	arg1	microarray					601:610	lectin-based protein microarray	580:610	lectin-based protein microarray	580:610	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	4	77	theme	protein	593:599	arg1	platforms					569:577	two platforms	565:577	two platforms: lectin-based protein microarray, and MALDI-MS	565:624	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	8	78	theme	line	1101:1104	arg1	IgA1/2G9					1106:1113	stable cell line IgA1/2G9	1089:1113	stable cell line IgA1/2G9 on the basal medium	1089:1133	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	5	79	theme	IgA	679:681	arg1	samples					668:674	the samples	664:674	the samples of IgA	664:681	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	3	80	theme	rapid	434:438	arg1	glycoprofiling					453:466	rapid and reliable glycoprofiling	434:466	rapid and reliable glycoprofiling of therapeutic proteins	434:490	Therefore, there is a demand for analytical techniques enabling rapid and reliable glycoprofiling of therapeutic proteins.
32298669	10	81	theme	metabolic	1493:1501	arg1	shift					1503:1507	the metabolic shift	1489:1507	the metabolic shift from glutamine to asparagine or feeding with glucose	1489:1560	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	11	82	theme	galactosylation	1852:1866	arg1	increase					1819:1826	increase	1819:1826	increase of both sialylation and galactosylation	1819:1866	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	11	82	theme	galactosylation	1852:1866	arg1	acid					1810:1813	succinic acid	1801:1813	succinic acid	1801:1813	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32298669	7	83	theme	sialic	1021:1026	arg1	acid					1028:1031	sialic acid	1021:1031	sialic acid	1021:1031	IgAs are effective as therapeutic agents in defense against viruses that use sialic acid as a receptor.
32298669	7	83	theme	sialic	1021:1026	arg1	receptor					1038:1045	a receptor	1036:1045	a receptor	1036:1045	IgAs are effective as therapeutic agents in defense against viruses that use sialic acid as a receptor.
32298669	5	84	with	lectins	747:753	arg1	specificity					768:778	specificity	768:778	specificity	768:778	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	5	84	with	lectins	747:753	arg1	evaluation					784:793	evaluation	784:793	evaluation	784:793	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	8	85	theme	basal	1122:1126	arg1	medium					1128:1133	the basal medium	1118:1133	the basal medium	1118:1133	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	0	86	theme	composition	19:29	arg1	Influence					0:8	Influence	0:8	Influence of media composition on recombinant monoclonal IgA1 glycosylation	0:74	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	12	87	theme	changes	1974:1980	arg1	mechanism					1950:1958	mechanism	1950:1958	mechanism of determined changes	1950:1980	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	3	88	theme	reliable	444:451	arg1	glycoprofiling					453:466	rapid and reliable glycoprofiling	434:466	rapid and reliable glycoprofiling of therapeutic proteins	434:490	Therefore, there is a demand for analytical techniques enabling rapid and reliable glycoprofiling of therapeutic proteins.
32298669	0	89	theme	recombinant	34:44	arg1	glycosylation					62:74	recombinant monoclonal IgA1 glycosylation	34:74	recombinant monoclonal IgA1 glycosylation	34:74	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	12	90	theme	further	1991:1997	arg1	investigation					1999:2011	further investigation	1991:2011	further investigation	1991:2011	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	6	91	theme	IgA1	930:933	arg1	samples					935:941	IgA1 samples	930:941	IgA1 samples	930:941	MALDI-MS was used for N-glycan analysis of IgA1 samples.
32298669	12	92	theme	effective	2062:2070	arg1	platform					2072:2079	effective platform	2062:2079	effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins	2062:2164	The elucidation of mechanism of determined changes requires further investigation, but the described analytical approach represent effective platform for determination, screening and evaluation of glycosylation of therapeutic proteins.
32298669	0	93	theme	IgA1	57:60	arg1	glycosylation					62:74	recombinant monoclonal IgA1 glycosylation	34:74	recombinant monoclonal IgA1 glycosylation	34:74	Influence of media composition on recombinant monoclonal IgA1 glycosylation analysed by lectin-based protein microarray and MALDI-MS.
32298669	9	94	theme	mannose	1422:1428	arg1	feeding					1430:1436	mannose feeding	1422:1436	mannose feeding	1422:1436	Decrease of lactate levels was observed during supplementation with succinic acid, asparagine, or with mannose feeding.
32298669	8	95	theme	different	1160:1168	arg1	conditions					1148:1157	different conditions	1138:1157	different conditions (different supplementation and feeding)	1138:1197	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	8	95	theme	different	1160:1168	arg1	supplementation					1170:1184	different supplementation	1160:1184	different supplementation	1160:1184	Dimeric IgA1 antibodies were produced by stable cell line IgA1/2G9 on the basal medium at different conditions (different supplementation and feeding) and we also evaluated the effect of different conditions on lactate production, which correlates with IgA productivity.
32298669	3	96	theme	proteins	483:490	arg1	glycoprofiling					453:466	rapid and reliable glycoprofiling	434:466	rapid and reliable glycoprofiling of therapeutic proteins	434:490	Therefore, there is a demand for analytical techniques enabling rapid and reliable glycoprofiling of therapeutic proteins.
32298669	10	97	theme	mannose	1586:1592	arg1	glycans					1599:1605	high mannose type glycans	1581:1605	high mannose type glycans what was confirmed also by MALDI-MS	1581:1641	We found by lectin-based microarray analysis that the metabolic shift from glutamine to asparagine or feeding with glucose caused increase of high mannose type glycans what was confirmed also by MALDI-MS.
32298669	4	98	dep	platforms	569:577	arg1	microarray					601:610	lectin-based protein microarray	580:610	lectin-based protein microarray	580:610	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	4	98	dep	platforms	569:577	arg1	MALDI-MS					617:624	MALDI-MS	617:624	MALDI-MS	617:624	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	4	98	dep	platforms	569:577	arg1	platforms					569:577	two platforms	565:577	two platforms: lectin-based protein microarray, and MALDI-MS	565:624	For the investigation of changes in glycan structures, we have employed two platforms: lectin-based protein microarray, and MALDI-MS.
32298669	5	99	dep	printed	688:694	arg1	incubated					721:729	incubated	721:729	incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins	721:884	In lectin-based microarray analysis, the samples of IgA were printed on the microarray slide, incubated with the set of lectins with various specificity and evaluation of changes in glycosylation was based on differences in reactivity of samples with lectins.
32298669	11	100	theme	IgA	1667:1669	arg1	glycosylation					1671:1683	IgA glycosylation	1667:1683	IgA glycosylation determined by lectin-based protein microarray	1667:1729	Among other changes in IgA glycosylation determined by lectin-based protein microarray were, for example, reduced galactosylation after supplementation with succinic acid and increase of both sialylation and galactosylation after supplementation with glutamine and feeding with mannose.
32991816	7	0	theme	fucose	1594:1599	arg1	residues					1601:1608	two terminal fucose residues	1581:1608	two terminal fucose residues	1581:1608	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	2	1	theme	mice	598:601	arg1	O-glycosylation					532:546	colonic mucin O-glycosylation	518:546	colonic mucin O-glycosylation	518:546	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	2	1	theme	mice	598:601	arg1	physiology					557:566	host physiology	552:566	host physiology	552:566	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	2	1	theme	mice	598:601	arg1	microbiota					506:515	the gut microbiota	498:515	the gut microbiota	498:515	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	3	2	theme	liver	685:689	arg1	proteome					691:698	liver proteome	685:698	liver proteome	685:698	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	2	3	theme	diet-fed	580:587	arg1	mice					598:601	high-fat diet-fed C57BL/6J mice	571:601	high-fat diet-fed C57BL/6J mice	571:601	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	7	4	theme	Parabacteroides	1428:1442	arg1	distasonis					1444:1453	the bacterium Parabacteroides distasonis	1414:1453	the bacterium Parabacteroides distasonis	1414:1453	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	8	5	theme	fiber	1737:1741	arg1	associations					1784:1795	associations	1784:1795	associations of these mucosal glycans with specific gut bacteria	1784:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	5	theme	fiber	1737:1741	arg1	impact					1719:1724	the impact	1715:1724	the impact of dietary fiber on the colonic mucin O-glycosylation	1715:1778	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	1	6	gly	O-glycosylated	170:183	arg1	mucins					185:190	highly O-glycosylated mucins	163:190	highly O-glycosylated mucins	163:190	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	8	7	theme	mucosal	1806:1812	arg1	glycans					1814:1820	these mucosal glycans	1800:1820	these mucosal glycans	1800:1820	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	3	8	theme	microbiota	705:714	arg1	composition					716:726	gut microbiota composition	701:726	gut microbiota composition	701:726	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	4	9	theme	high	853:856	arg1	modifications					870:882	all high fat-induced modifications	849:882	all high fat-induced modifications	849:882	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	3	10	theme	acid	751:754	arg1	production					756:765	short-chain fatty acid production	733:765	short-chain fatty acid production	733:765	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	8	11	theme	gut	1836:1838	arg1	bacteria					1840:1847	specific gut bacteria	1827:1847	specific gut bacteria	1827:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	4	12	theme	fat-induced	858:868	arg1	modifications					870:882	all high fat-induced modifications	849:882	all high fat-induced modifications	849:882	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	7	13	theme	distasonis	1444:1453	arg1	abundance					1401:1409	the relative abundance	1388:1409	the relative abundance of the bacterium Parabacteroides distasonis	1388:1453	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	3	14	contain	had	628:630	arg1	group					622:626	The high-fat diet group	604:626	The high-fat diet group	604:626	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	3	14	contain	had	628:630	arg2	tolerance					663:671	impaired glucose tolerance	646:671	impaired glucose tolerance	646:671	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	3	15	theme	short-chain	733:743	arg1	acid					751:754	short-chain fatty acid	733:754	short-chain fatty acid production	733:765	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	1	16	from	impact	257:262	arg1	O-glycosylation					300:314	colonic mucin O-glycosylation	286:314	colonic mucin O-glycosylation	286:314	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	1	16	from	impact	257:262	arg1	associations					324:335	its associations	320:335	its associations with the gut microbiota	320:359	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	4	17	from	increase	931:938	arg1	abundance					956:964	the relative abundance	943:964	the relative abundance of bacterial families with known fiber digesters	943:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	8	18	with	impact	1719:1724	arg1	bacteria					1840:1847	specific gut bacteria	1827:1847	specific gut bacteria	1827:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	2	19	theme	colonic	518:524	arg1	O-glycosylation					532:546	colonic mucin O-glycosylation	518:546	colonic mucin O-glycosylation	518:546	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	3	20	theme	normal	779:784	arg1	diet					791:794	normal chow diet	779:794	normal chow diet group	779:800	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	5	21	theme	mucin	1074:1078	arg1	O-glycosylation					1080:1094	colonic mucin O-glycosylation	1066:1094	colonic mucin O-glycosylation	1066:1094	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	6	22	theme	network	1258:1264	arg1	analysis					1266:1273	Correlation network analysis	1246:1273	Correlation network analysis	1246:1273	Correlation network analysis revealed previously undescribed associations between specific bacteria and mucin glycan structures.
32991816	2	23	theme	host	552:555	arg1	physiology					557:566	host physiology	552:566	host physiology	552:566	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	6	24	theme	glycan	1356:1361	arg1	structures					1363:1372	mucin glycan structures	1350:1372	mucin glycan structures	1350:1372	Correlation network analysis revealed previously undescribed associations between specific bacteria and mucin glycan structures.
32991816	3	25	theme	diet	617:620	arg1	group					622:626	The high-fat diet group	604:626	The high-fat diet group	604:626	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	1	26	theme	colonic	129:135	arg1	layer					143:147	The colonic mucus layer	125:147	The colonic mucus layer	125:147	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	1	26	theme	colonic	129:135	arg1	vital					196:200	vital	196:200	vital	196:200	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	4	27	theme	bacterial	969:977	arg1	families					979:986	bacterial families	969:986	bacterial families with known fiber digesters	969:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	2	28	theme	omics	407:411	arg1	glycomics					434:442	glycomics	434:442	glycomics	434:442	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	2	28	theme	omics	407:411	arg1	techniques					413:422	omics techniques	407:422	omics techniques including glycomics	407:442	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	7	29	contain	containing	1570:1579	arg2	residues					1601:1608	two terminal fucose residues	1581:1608	two terminal fucose residues	1581:1608	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	7	29	contain	containing	1570:1579	arg1	glycans					1562:1568	glycans	1562:1568	glycans containing two terminal fucose residues	1562:1608	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	2	30	theme	dietary	469:475	arg1	consumption					483:493	dietary fiber consumption	469:493	dietary fiber consumption	469:493	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	7	31	contain	containing	1500:1509	arg1	structures					1489:1498	glycan structures	1482:1498	glycan structures containing one terminal fucose	1482:1529	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	7	31	contain	containing	1500:1509	arg2	fucose					1524:1529	one terminal fucose	1511:1529	one terminal fucose	1511:1529	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	8	32	from	impact	1719:1724	arg1	O-glycosylation					1764:1778	the colonic mucin O-glycosylation	1746:1778	the colonic mucin O-glycosylation	1746:1778	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	0	33	theme	colonic	68:74	arg1	O-glycosylation					82:96	colonic mucin O-glycosylation and specific gut bacteria	68:122	O-glycosylation	82:96	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	5	34	theme	diet	1150:1153	arg1	groups					1155:1160	the normal chow and high-fat diet groups	1121:1160	the normal chow and high-fat diet groups	1121:1160	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	6	35	theme	specific	1328:1335	arg1	bacteria					1337:1344	specific bacteria	1328:1344	specific bacteria	1328:1344	Correlation network analysis revealed previously undescribed associations between specific bacteria and mucin glycan structures.
32991816	0	36	from	Changes	0:6	arg1	mice					35:38	mice	35:38	mice	35:38	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	0	36	from	Changes	0:6	arg1	intake					25:30	dietary fiber intake	11:30	dietary fiber intake	11:30	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	1	37	theme	gut	346:348	arg1	microbiota					350:359	the gut microbiota	342:359	the gut microbiota	342:359	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	7	38	theme	sulfate	1656:1662	arg1	residue					1664:1670	a sulfate residue	1654:1670	a sulfate residue	1654:1670	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	0	39	theme	specific	102:109	arg1	bacteria					115:122	colonic mucin O-glycosylation and specific gut bacteria	68:122	bacteria	115:122	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	5	40	theme	normal	1125:1130	arg1	chow					1132:1135	normal chow	1125:1135	normal chow	1125:1135	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	7	41	theme	relative	1392:1399	arg1	abundance					1401:1409	the relative abundance	1388:1409	the relative abundance of the bacterium Parabacteroides distasonis	1388:1453	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	4	42	theme	higher	1021:1026	arg1	concentration					1039:1051	a higher propionate concentration	1019:1051	a higher propionate concentration	1019:1051	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	2	43	theme	consumption	483:493	arg1	effect					459:464	the effect	455:464	the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice	455:601	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	4	44	from	concentration	1039:1051	arg1	abundance					956:964	the relative abundance	943:964	the relative abundance of bacterial families with known fiber digesters	943:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	2	45	theme	techniques	413:422	arg1	array					398:402	an array	395:402	an array of omics techniques including glycomics	395:442	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	0	46	theme	dietary	11:17	arg1	intake					25:30	dietary fiber intake	11:30	dietary fiber intake	11:30	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	1	47	theme	changes	275:281	arg1	impact					257:262	the impact	253:262	the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota	253:359	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	4	48	theme	fiber	999:1003	arg1	digesters					1005:1013	known fiber digesters	993:1013	known fiber digesters	993:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	3	49	theme	impaired	646:653	arg1	tolerance					663:671	impaired glucose tolerance	646:671	impaired glucose tolerance	646:671	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	4	50	theme	fiber	817:821	arg1	inclusion					823:831	dietary fiber inclusion	809:831	dietary fiber inclusion	809:831	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	1	51	theme	colonic	286:292	arg1	O-glycosylation					300:314	colonic mucin O-glycosylation	286:314	colonic mucin O-glycosylation	286:314	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	5	52	dep	chow	1132:1135	arg1	the					1121:1123	the	1121:1123	the	1121:1123	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	5	53	theme	dietary	1169:1175	arg1	intervention					1183:1194	dietary fiber intervention	1169:1194	dietary fiber intervention	1169:1194	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	2	54	gly	O-glycosylation	532:546	arg1	mice					598:601	high-fat diet-fed C57BL/6J mice	571:601	high-fat diet-fed C57BL/6J mice	571:601	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	8	55	theme	comprehensive	1691:1703	arg1	report					1705:1710	the first comprehensive report	1681:1710	the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria	1681:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	55	theme	comprehensive	1691:1703	arg1	This					1673:1676	This	1673:1676	This	1673:1676	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	56	theme	colonic	1750:1756	arg1	O-glycosylation					1764:1778	the colonic mucin O-glycosylation	1746:1778	the colonic mucin O-glycosylation	1746:1778	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	1	57	theme	microbiota	224:233	arg1	interactions					235:246	host-gut microbiota interactions	215:246	host-gut microbiota interactions	215:246	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	7	58	theme	terminal	1585:1592	arg1	residues					1601:1608	two terminal fucose residues	1581:1608	two terminal fucose residues	1581:1608	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	3	59	theme	gut	701:703	arg1	composition					716:726	gut microbiota composition	701:726	gut microbiota composition	701:726	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	6	60	theme	mucin	1350:1354	arg1	structures					1363:1372	mucin glycan structures	1350:1372	mucin glycan structures	1350:1372	Correlation network analysis revealed previously undescribed associations between specific bacteria and mucin glycan structures.
32991816	2	61	theme	C57BL/6J	589:596	arg1	mice					598:601	high-fat diet-fed C57BL/6J mice	571:601	high-fat diet-fed C57BL/6J mice	571:601	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	1	62	with	O-glycosylation	300:314	arg1	microbiota					350:359	the gut microbiota	342:359	the gut microbiota	342:359	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	8	63	theme	impact	1719:1724	arg1	report					1705:1710	the first comprehensive report	1681:1710	the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria	1681:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	63	theme	impact	1719:1724	arg1	This					1673:1676	This	1673:1676	This	1673:1676	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	64	theme	associations	1784:1795	arg1	report					1705:1710	the first comprehensive report	1681:1710	the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria	1681:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	64	theme	associations	1784:1795	arg1	This					1673:1676	This	1673:1676	This	1673:1676	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	2	65	theme	high-fat	571:578	arg1	mice					598:601	high-fat diet-fed C57BL/6J mice	571:601	high-fat diet-fed C57BL/6J mice	571:601	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	8	66	theme	dietary	1729:1735	arg1	fiber					1737:1741	dietary fiber	1729:1741	dietary fiber	1729:1741	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	7	67	theme	terminal	1515:1522	arg1	fucose					1524:1529	one terminal fucose	1511:1529	one terminal fucose	1511:1529	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	6	68	theme	undescribed	1295:1305	arg1	associations					1307:1318	previously undescribed associations	1284:1318	previously undescribed associations between specific bacteria and mucin glycan structures	1284:1372	Correlation network analysis revealed previously undescribed associations between specific bacteria and mucin glycan structures.
32991816	8	69	theme	glycans	1814:1820	arg1	associations					1784:1795	associations	1784:1795	associations of these mucosal glycans with specific gut bacteria	1784:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	69	theme	glycans	1814:1820	arg1	impact					1719:1724	the impact	1715:1724	the impact of dietary fiber on the colonic mucin O-glycosylation	1715:1778	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	1	70	theme	O-glycosylated	170:183	arg1	mucins					185:190	highly O-glycosylated mucins	163:190	highly O-glycosylated mucins	163:190	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	8	71	theme	specific	1827:1834	arg1	bacteria					1840:1847	specific gut bacteria	1827:1847	specific gut bacteria	1827:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	2	72	theme	mucin	526:530	arg1	O-glycosylation					532:546	colonic mucin O-glycosylation	518:546	colonic mucin O-glycosylation	518:546	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	7	73	theme	glycan	1482:1487	arg1	structures					1489:1498	glycan structures	1482:1498	glycan structures containing one terminal fucose	1482:1529	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	3	74	theme	fatty	745:749	arg1	acid					751:754	short-chain fatty acid	733:754	short-chain fatty acid production	733:765	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	5	75	from	alterations	1214:1224	arg1	O-glycosylation					1229:1243	O-glycosylation	1229:1243	O-glycosylation	1229:1243	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	2	76	used	used	390:393	arg2	we					387:388	we	387:388	we	387:388	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	3	77	theme	chow	786:789	arg1	diet					791:794	normal chow diet	779:794	normal chow diet group	779:800	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	6	78	theme	Correlation	1246:1256	arg1	analysis					1266:1273	Correlation network analysis	1246:1273	Correlation network analysis	1246:1273	Correlation network analysis revealed previously undescribed associations between specific bacteria and mucin glycan structures.
32991816	3	79	theme	high-fat	608:615	arg1	group					622:626	The high-fat diet group	604:626	The high-fat diet group	604:626	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	4	80	theme	specific	900:907	arg1	changes					909:915	specific changes	900:915	specific changes	900:915	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	7	81	theme	bacterium	1418:1426	arg1	distasonis					1444:1453	the bacterium Parabacteroides distasonis	1414:1453	the bacterium Parabacteroides distasonis	1414:1453	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	4	82	dep	changes	909:915	arg1	including					918:926	including	918:926	including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration	918:1051	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	5	83	theme	colonic	1066:1072	arg1	O-glycosylation					1080:1094	colonic mucin O-glycosylation	1066:1094	colonic mucin O-glycosylation	1066:1094	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	1	84	theme	mucus	137:141	arg1	layer					143:147	The colonic mucus layer	125:147	The colonic mucus layer	125:147	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	1	84	theme	mucus	137:141	arg1	vital					196:200	vital	196:200	vital	196:200	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	2	85	theme	fiber	477:481	arg1	consumption					483:493	dietary fiber consumption	469:493	dietary fiber consumption	469:493	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	0	86	theme	mucin	76:80	arg1	O-glycosylation					82:96	colonic mucin O-glycosylation and specific gut bacteria	68:122	O-glycosylation	82:96	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	5	87	theme	high-fat	1141:1148	arg1	diet					1150:1153	high-fat diet	1141:1153	high-fat diet	1141:1153	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	4	88	theme	families	979:986	arg1	abundance					956:964	the relative abundance	943:964	the relative abundance of bacterial families with known fiber digesters	943:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	3	89	dep	diet	791:794	arg1	group					796:800	group	796:800	normal chow diet group	779:800	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	1	90	with	associations	324:335	arg1	microbiota					350:359	the gut microbiota	342:359	the gut microbiota	342:359	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	2	91	theme	gut	502:504	arg1	microbiota					506:515	the gut microbiota	498:515	the gut microbiota	498:515	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	0	92	theme	gut	111:113	arg1	bacteria					115:122	colonic mucin O-glycosylation and specific gut bacteria	68:122	bacteria	115:122	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	4	93	theme	relative	947:954	arg1	abundance					956:964	the relative abundance	943:964	the relative abundance of bacterial families with known fiber digesters	943:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	2	94	from	effect	459:464	arg1	O-glycosylation					532:546	colonic mucin O-glycosylation	518:546	colonic mucin O-glycosylation	518:546	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	2	94	from	effect	459:464	arg1	physiology					557:566	host physiology	552:566	host physiology	552:566	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	2	94	from	effect	459:464	arg1	microbiota					506:515	the gut microbiota	498:515	the gut microbiota	498:515	Here, we used an array of omics techniques including glycomics to examine the effect of dietary fiber consumption on the gut microbiota, colonic mucin O-glycosylation and host physiology of high-fat diet-fed C57BL/6J mice.
32991816	5	95	theme	chow	1132:1135	arg1	groups					1155:1160	the normal chow and high-fat diet groups	1121:1160	the normal chow and high-fat diet groups	1121:1160	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	8	96	from	report	1705:1710	arg1	O-glycosylation					1764:1778	the colonic mucin O-glycosylation	1746:1778	the colonic mucin O-glycosylation	1746:1778	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	97	from	associations	1784:1795	arg1	O-glycosylation					1764:1778	the colonic mucin O-glycosylation	1746:1778	the colonic mucin O-glycosylation	1746:1778	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	0	98	theme	fiber	19:23	arg1	intake					25:30	dietary fiber intake	11:30	dietary fiber intake	11:30	Changes in dietary fiber intake in mice reveal associations between colonic mucin O-glycosylation and specific gut bacteria.
32991816	1	99	theme	dietary	267:273	arg1	changes					275:281	dietary changes	267:281	dietary changes	267:281	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	4	100	theme	propionate	1028:1037	arg1	concentration					1039:1051	a higher propionate concentration	1019:1051	a higher propionate concentration	1019:1051	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	8	101	from	O-glycosylation	1764:1778	arg1	report					1705:1710	the first comprehensive report	1681:1710	the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria	1681:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	101	from	O-glycosylation	1764:1778	arg1	This					1673:1676	This	1673:1676	This	1673:1676	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	5	102	theme	major	1208:1212	arg1	alterations					1214:1224	major alterations	1208:1224	major alterations in O-glycosylation	1208:1243	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	4	103	theme	known	993:997	arg1	digesters					1005:1013	known fiber digesters	993:1013	known fiber digesters	993:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	4	104	theme	dietary	809:815	arg1	inclusion					823:831	dietary fiber inclusion	809:831	dietary fiber inclusion	809:831	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	1	105	theme	mucin	294:298	arg1	O-glycosylation					300:314	colonic mucin O-glycosylation	286:314	colonic mucin O-glycosylation	286:314	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
32991816	7	106	theme	N-acetylneuraminic	1626:1643	arg1	acid					1645:1648	an N-acetylneuraminic acid	1623:1648	an N-acetylneuraminic acid	1623:1648	For example, the relative abundance of the bacterium Parabacteroides distasonis positively correlated with glycan structures containing one terminal fucose and correlated negatively with glycans containing two terminal fucose residues or with both an N-acetylneuraminic acid and a sulfate residue.
32991816	4	107	with	families	979:986	arg1	digesters					1005:1013	known fiber digesters	993:1013	known fiber digesters	993:1013	While dietary fiber inclusion did not reverse all high fat-induced modifications, it resulted in specific changes, including an increase in the relative abundance of bacterial families with known fiber digesters and a higher propionate concentration.
32991816	8	108	theme	first	1685:1689	arg1	report					1705:1710	the first comprehensive report	1681:1710	the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria	1681:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	108	theme	first	1685:1689	arg1	This					1673:1676	This	1673:1676	This	1673:1676	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	8	109	with	associations	1784:1795	arg1	bacteria					1840:1847	specific gut bacteria	1827:1847	specific gut bacteria	1827:1847	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	5	110	theme	fiber	1177:1181	arg1	intervention					1183:1194	dietary fiber intervention	1169:1194	dietary fiber intervention	1169:1194	Conversely, colonic mucin O-glycosylation remained similar between the normal chow and high-fat diet groups, while dietary fiber intervention resulted in major alterations in O-glycosylation.
32991816	3	111	theme	glucose	655:661	arg1	tolerance					663:671	impaired glucose tolerance	646:671	impaired glucose tolerance	646:671	The high-fat diet group had significantly impaired glucose tolerance and altered liver proteome, gut microbiota composition, and short-chain fatty acid production compared to normal chow diet group.
32991816	8	112	theme	mucin	1758:1762	arg1	O-glycosylation					1764:1778	the colonic mucin O-glycosylation	1746:1778	the colonic mucin O-glycosylation	1746:1778	This is the first comprehensive report of the impact of dietary fiber on the colonic mucin O-glycosylation and associations of these mucosal glycans with specific gut bacteria.
32991816	1	113	theme	host-gut	215:222	arg1	interactions					235:246	host-gut microbiota interactions	215:246	host-gut microbiota interactions	215:246	The colonic mucus layer, comprised of highly O-glycosylated mucins, is vital to mediating host-gut microbiota interactions, yet the impact of dietary changes on colonic mucin O-glycosylation and its associations with the gut microbiota remains unexplored.
34826451	1	0	theme	nutritious	152:161	arg1	Ovalbumin					126:134	Ovalbumin	126:134	Ovalbumin (OVA)	126:140	Ovalbumin (OVA) is a high nutritious protein, but the poor emulsibility limited its application.
34826451	1	0	theme	nutritious	152:161	arg1	protein					163:169	a high nutritious protein	145:169	a high nutritious protein	145:169	Ovalbumin (OVA) is a high nutritious protein, but the poor emulsibility limited its application.
34826451	6	1	theme	slower	995:1000	arg1	profiles					1015:1022	slower transmission profiles	995:1022	slower transmission profiles	995:1022	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	6	1	theme	slower	995:1000	arg1	well					1074:1077	well	1074:1077	well	1074:1077	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	7	2	theme	OVA	1232:1234	arg1	properties					1218:1227	the emulsifying properties	1202:1227	the emulsifying properties of OVA	1202:1234	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	4	3	theme	fluorescence	540:551	arg1	spectroscopy					553:564	fluorescence spectroscopy	540:564	fluorescence spectroscopy	540:564	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	7	4	theme	emulsifying	1206:1216	arg1	properties					1218:1227	the emulsifying properties	1202:1227	the emulsifying properties of OVA	1202:1234	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	6	5	theme	scanning	893:900	arg1	results					902:908	confocal laser scanning results	878:908	confocal laser scanning results	878:908	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	4	6	theme	UV	570:571	arg1	spectroscopy					573:584	UV spectroscopy	570:584	UV spectroscopy	570:584	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	0	7	theme	emulsibility	100:111	arg1	improvement					113:123	its emulsibility improvement	96:123	its emulsibility improvement	96:123	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	6	8	theme	laser	887:891	arg1	results					902:908	confocal laser scanning results	878:908	confocal laser scanning results	878:908	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	3	9	dep	degree	376:381	arg1	DG					384:385	DG	384:385	DG	384:385	Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction.
34826451	3	9	dep	degree	376:381	arg1	browning					391:398	browning	391:398	browning	391:398	Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction.
34826451	6	10	theme	emulsibility	1095:1106	arg1	improvement					1108:1118	the emulsibility improvement	1091:1118	the emulsibility improvement of OVA	1091:1125	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	6	11	theme	OVA	1123:1125	arg1	improvement					1108:1118	the emulsibility improvement	1091:1118	the emulsibility improvement of OVA	1091:1125	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	5	12	theme	emulsion	715:722	arg1	ESI					741:743	ESI	741:743	ESI	741:743	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	5	12	theme	emulsion	715:722	arg1	index					734:738	emulsion stability index	715:738	emulsion stability index (ESI)	715:744	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	6	13	theme	confocal	878:885	arg1	results					902:908	confocal laser scanning results	878:908	confocal laser scanning results	878:908	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	4	14	from	Variations	466:475	arg1	structure					490:498	molecular structure	480:498	molecular structure of OVA	480:505	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	5	15	theme	OVA-Dex	766:772	arg1	glycoconjugates					774:788	OVA-Dex glycoconjugates	766:788	OVA-Dex glycoconjugates	766:788	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	4	16	theme	glycoconjugate	633:646	arg1	generation					619:628	the generation	615:628	the generation of glycoconjugate	615:646	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	5	17	theme	stability	724:732	arg1	ESI					741:743	ESI	741:743	ESI	741:743	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	5	17	theme	stability	724:732	arg1	index					734:738	emulsion stability index	715:738	emulsion stability index (ESI)	715:744	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	3	18	dep	DG	384:385	arg1	intensity					400:408	intensity	400:408	intensity	400:408	Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction.
34826451	5	19	theme	glycoconjugates	774:788	arg1	emulsion					754:761	the emulsion	750:761	the emulsion of OVA-Dex glycoconjugates	750:788	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	5	20	theme	glycosylation	841:853	arg1	temperature					855:865	glycosylation temperature	841:865	glycosylation temperature	841:865	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	3	21	theme	glycosylation	362:374	arg1	degree					376:381	glycosylation degree	362:381	glycosylation degree (DG and browning intensity)	362:409	Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction.
34826451	0	22	theme	Molecular	0:8	arg1	modification					20:31	Molecular structure modification	0:31	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.	0:124	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	6	23	theme	uniform	969:975	arg1	distribution					977:988	more uniform distribution	964:988	more uniform distribution	964:988	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	2	24	with	OVA	254:256	arg1	Dex					272:274	Dex	272:274	Dex	272:274	The present study glycosylated OVA with dextran (Dex) by controlled wetheating (60-90 °C for 3 h).
34826451	2	24	with	OVA	254:256	arg1	dextran					263:269	dextran	263:269	dextran (Dex)	263:275	The present study glycosylated OVA with dextran (Dex) by controlled wetheating (60-90 °C for 3 h).
34826451	1	25	theme	poor	180:183	arg1	emulsibility					185:196	the poor emulsibility	176:196	the poor emulsibility	176:196	Ovalbumin (OVA) is a high nutritious protein, but the poor emulsibility limited its application.
34826451	5	26	theme	activity	690:697	arg1	index					699:703	Emulsifying activity index	678:703	Emulsifying activity index (EAI)	678:709	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	5	26	theme	activity	690:697	arg1	EAI					706:708	EAI	706:708	EAI	706:708	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	7	27	theme	available	1174:1182	arg1	reaction					1159:1166	controlled glycosylation reaction	1134:1166	controlled glycosylation reaction	1134:1166	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	7	27	theme	available	1174:1182	arg1	method					1184:1189	an available method	1171:1189	an available method to improve the emulsifying properties of OVA	1171:1234	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	2	28	theme	controlled	280:289	arg1	wetheating					291:300	controlled wetheating	280:300	controlled wetheating (60-90 °C for 3 h)	280:319	The present study glycosylated OVA with dextran (Dex) by controlled wetheating (60-90 °C for 3 h).
34826451	6	29	theme	centrifugal	1050:1060	arg1	analysis					1062:1069	LUMiSizer centrifugal analysis	1040:1069	LUMiSizer centrifugal analysis	1040:1069	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	6	30	theme	LUMiSizer	1040:1048	arg1	analysis					1062:1069	LUMiSizer centrifugal analysis	1040:1069	LUMiSizer centrifugal analysis	1040:1069	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	4	31	from	successes	602:610	arg1	generation					619:628	the generation	615:628	the generation of glycoconjugate	615:646	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	3	32	theme	higher	416:421	arg1	temperature					423:433	higher temperature	416:433	higher temperature	416:433	Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction.
34826451	0	33	theme	ovalbumin	36:44	arg1	modification					20:31	Molecular structure modification	0:31	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.	0:124	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	0	34	mod	modification	20:31	arg3	structure					10:18	Molecular structure modification	0:31	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.	0:124	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	0	34	mod	modification	20:31	arg1	ovalbumin					36:44	ovalbumin	36:44	ovalbumin	36:44	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	2	35	theme	present	227:233	arg1	study					235:239	The present study	223:239	The present study	223:239	The present study glycosylated OVA with dextran (Dex) by controlled wetheating (60-90 °C for 3 h).
34826451	7	36	theme	controlled	1134:1143	arg1	reaction					1159:1166	controlled glycosylation reaction	1134:1166	controlled glycosylation reaction	1134:1166	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	7	36	theme	controlled	1134:1143	arg1	method					1184:1189	an available method	1171:1189	an available method to improve the emulsifying properties of OVA	1171:1234	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	4	37	theme	OVA	503:505	arg1	structure					490:498	molecular structure	480:498	molecular structure of OVA	480:505	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	2	38	dep	wetheating	291:300	arg1	60-90 °C					303:310	60-90 °C	303:310	60-90 °C for 3 h	303:318	The present study glycosylated OVA with dextran (Dex) by controlled wetheating (60-90 °C for 3 h).
34826451	0	39	theme	controlled	54:63	arg1	glycosylation					65:77	controlled glycosylation	54:77	controlled glycosylation with dextran for its emulsibility improvement	54:123	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	6	40	theme	smaller	947:953	arg1	size					955:958	smaller size	947:958	smaller size	947:958	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	7	41	theme	glycosylation	1145:1157	arg1	reaction					1159:1166	controlled glycosylation reaction	1134:1166	controlled glycosylation reaction	1134:1166	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	7	41	theme	glycosylation	1145:1157	arg1	method					1184:1189	an available method	1171:1189	an available method to improve the emulsifying properties of OVA	1171:1234	Thus, controlled glycosylation reaction is an available method to improve the emulsifying properties of OVA.
34826451	4	42	theme	flexible	658:665	arg1	structure					667:675	more flexible structure	653:675	more flexible structure	653:675	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	5	43	theme	Emulsifying	678:688	arg1	index					699:703	Emulsifying activity index	678:703	Emulsifying activity index (EAI)	678:709	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	5	43	theme	Emulsifying	678:688	arg1	EAI					706:708	EAI	706:708	EAI	706:708	Emulsifying activity index (EAI) and emulsion stability index (ESI) for the emulsion of OVA-Dex glycoconjugates were significantly enhanced with the increasing of glycosylation temperature.
34826451	0	44	with	glycosylation	65:77	arg1	dextran					84:90	dextran	84:90	dextran	84:90	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	1	45	theme	high	147:150	arg1	Ovalbumin					126:134	Ovalbumin	126:134	Ovalbumin (OVA)	126:140	Ovalbumin (OVA) is a high nutritious protein, but the poor emulsibility limited its application.
34826451	1	45	theme	high	147:150	arg1	protein					163:169	a high nutritious protein	145:169	a high nutritious protein	145:169	Ovalbumin (OVA) is a high nutritious protein, but the poor emulsibility limited its application.
34826451	4	46	theme	molecular	480:488	arg1	structure					490:498	molecular structure	480:498	molecular structure of OVA	480:505	Variations in molecular structure of OVA were analyzed by SDS-PAGE, FTIR, fluorescence spectroscopy and UV spectroscopy, which verified successes in the generation of glycoconjugate with more flexible structure.
34826451	6	47	theme	transmission	1002:1013	arg1	profiles					1015:1022	slower transmission profiles	995:1022	slower transmission profiles	995:1022	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	6	47	theme	transmission	1002:1013	arg1	well					1074:1077	well	1074:1077	well	1074:1077	Moreover, confocal laser scanning results revealed that the emulsion exhibited smaller size and more uniform distribution, and slower transmission profiles were checked by LUMiSizer centrifugal analysis as well, confirming the emulsibility improvement of OVA.
34826451	0	48	theme	structure	10:18	arg1	modification					20:31	Molecular structure modification	0:31	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.	0:124	Molecular structure modification of ovalbumin through controlled glycosylation with dextran for its emulsibility improvement.
34826451	3	49	theme	inductive	341:349	arg1	factor					351:356	an inductive factor	338:356	an inductive factor for glycosylation degree (DG and browning intensity)	338:409	Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction.
34826451	3	49	theme	inductive	341:349	arg1	Temperature					322:332	Temperature	322:332	Temperature	322:332	Temperature was an inductive factor for glycosylation degree (DG and browning intensity), and higher temperature could accelerate the reaction.
32617953	4	0	theme	technology	547:556	arg1	use					535:537	use	535:537	use of this technology to prepare a collection of plant cell wall glycans for cell wall research	535:630	We recently made use of this technology to prepare a collection of plant cell wall glycans for cell wall research.
32617953	3	1	dep	assembly	412:419	arg1	emerged					424:430	emerged	424:430	emerged	424:430	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	2	2	dep	possibility	299:309	arg1	introduce					314:322	introduce	314:322	to introduce chemical handles	311:339	Their well-defined structure and high purity prevents misinterpretations of experimental data, and the possibility to introduce chemical handles provides means for easier localization and detection.
32617953	4	3	theme	glycans	601:607	arg1	collection					571:580	a collection	569:580	a collection of plant cell wall glycans for cell wall research	569:630	We recently made use of this technology to prepare a collection of plant cell wall glycans for cell wall research.
32617953	3	4	contain	has	432:434	arg2	method					451:456	a powerful new method	436:456	a powerful new method for the efficient preparation of oligosaccharide libraries	436:515	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	3	4	contain	has	432:434	arg1	assembly					412:419	Automated glycan assembly	395:419	Automated glycan assembly as emerged	395:430	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	4	5	theme	wall	618:621	arg1	research					623:630	cell wall research	613:630	cell wall research	613:630	We recently made use of this technology to prepare a collection of plant cell wall glycans for cell wall research.
32617953	3	6	theme	Automated	395:403	arg1	assembly					412:419	Automated glycan assembly	395:419	Automated glycan assembly as emerged	395:430	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	5	7	theme	automated	691:699	arg1	synthesis					701:709	the automated synthesis	687:709	the automated synthesis of oligosaccharides	687:729	In this chapter, detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays are described.
32617953	1	8	theme	Synthetic	63:71	arg1	tools					124:128	promising molecular tools	104:128	promising molecular tools for investigating the structure and function of plant cell walls	104:193	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	8	theme	Synthetic	63:71	arg1	oligosaccharides					83:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	4	9	theme	cell	613:616	arg1	research					623:630	cell wall research	613:630	cell wall research	613:630	We recently made use of this technology to prepare a collection of plant cell wall glycans for cell wall research.
32617953	1	10	theme	cell	73:76	arg1	tools					124:128	promising molecular tools	104:128	promising molecular tools for investigating the structure and function of plant cell walls	104:193	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	10	theme	cell	73:76	arg1	oligosaccharides					83:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	11	theme	plant	178:182	arg1	walls					189:193	plant cell walls	178:193	plant cell walls	178:193	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	3	12	theme	powerful	438:445	arg1	method					451:456	a powerful new method	436:456	a powerful new method for the efficient preparation of oligosaccharide libraries	436:515	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	1	13	theme	wall	78:81	arg1	tools					124:128	promising molecular tools	104:128	promising molecular tools for investigating the structure and function of plant cell walls	104:193	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	13	theme	wall	78:81	arg1	oligosaccharides					83:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	14	theme	cell	184:187	arg1	walls					189:193	plant cell walls	178:193	plant cell walls	178:193	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	0	15	theme	Glycan	10:15	arg1	Assembly					17:24	Automated Glycan Assembly	0:24	Automated Glycan Assembly of Plant Cell Wall	0:43	Automated Glycan Assembly of Plant Cell Wall Oligosaccharides.
32617953	5	16	theme	detailed	650:657	arg1	procedures					672:681	detailed experimental procedures	650:681	detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays	650:773	In this chapter, detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays are described.
32617953	5	17	from	use	750:752	arg1	assays					768:773	biological assays	757:773	biological assays	757:773	In this chapter, detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays are described.
32617953	1	18	theme	walls	189:193	arg1	function					166:173	function	166:173	function	166:173	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	18	theme	walls	189:193	arg1	structure					152:160	structure	152:160	structure	152:160	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	0	19	theme	Automated	0:8	arg1	Assembly					17:24	Automated Glycan Assembly	0:24	Automated Glycan Assembly of Plant Cell Wall	0:43	Automated Glycan Assembly of Plant Cell Wall Oligosaccharides.
32617953	4	20	theme	plant	585:589	arg1	glycans					601:607	plant cell wall glycans	585:607	plant cell wall glycans	585:607	We recently made use of this technology to prepare a collection of plant cell wall glycans for cell wall research.
32617953	5	21	theme	experimental	659:670	arg1	procedures					672:681	detailed experimental procedures	650:681	detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays	650:773	In this chapter, detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays are described.
32617953	3	22	theme	glycan	405:410	arg1	assembly					412:419	Automated glycan assembly	395:419	Automated glycan assembly as emerged	395:430	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	1	23	theme	promising	104:112	arg1	tools					124:128	promising molecular tools	104:128	promising molecular tools for investigating the structure and function of plant cell walls	104:193	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	23	theme	promising	104:112	arg1	oligosaccharides					83:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	3	24	theme	oligosaccharide	491:505	arg1	libraries					507:515	oligosaccharide libraries	491:515	oligosaccharide libraries	491:515	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	4	25	theme	wall	596:599	arg1	glycans					601:607	plant cell wall glycans	585:607	plant cell wall glycans	585:607	We recently made use of this technology to prepare a collection of plant cell wall glycans for cell wall research.
32617953	1	26	theme	molecular	114:122	arg1	tools					124:128	promising molecular tools	104:128	promising molecular tools for investigating the structure and function of plant cell walls	104:193	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	1	26	theme	molecular	114:122	arg1	oligosaccharides					83:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides	63:98	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	3	27	theme	libraries	507:515	arg1	preparation					476:486	the efficient preparation	462:486	the efficient preparation of oligosaccharide libraries	462:515	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	0	28	theme	Cell	35:38	arg1	Wall					40:43	Plant Cell Wall	29:43	Plant Cell Wall	29:43	Automated Glycan Assembly of Plant Cell Wall Oligosaccharides.
32617953	4	29	theme	cell	591:594	arg1	glycans					601:607	plant cell wall glycans	585:607	plant cell wall glycans	585:607	We recently made use of this technology to prepare a collection of plant cell wall glycans for cell wall research.
32617953	0	30	theme	Plant	29:33	arg1	Wall					40:43	Plant Cell Wall	29:43	Plant Cell Wall	29:43	Automated Glycan Assembly of Plant Cell Wall Oligosaccharides.
32617953	3	31	theme	new	447:449	arg1	method					451:456	a powerful new method	436:456	a powerful new method for the efficient preparation of oligosaccharide libraries	436:515	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	2	32	dep	chemical	324:331	arg1	handles					333:339	handles	333:339	handles	333:339	Their well-defined structure and high purity prevents misinterpretations of experimental data, and the possibility to introduce chemical handles provides means for easier localization and detection.
32617953	0	33	theme	Wall	40:43	arg1	Assembly					17:24	Automated Glycan Assembly	0:24	Automated Glycan Assembly of Plant Cell Wall	0:43	Automated Glycan Assembly of Plant Cell Wall Oligosaccharides.
32617953	2	34	theme	high	229:232	arg1	purity					234:239	high purity	229:239	high purity	229:239	Their well-defined structure and high purity prevents misinterpretations of experimental data, and the possibility to introduce chemical handles provides means for easier localization and detection.
32617953	2	35	theme	easier	360:365	arg1	localization					367:378	easier localization	360:378	easier localization	360:378	Their well-defined structure and high purity prevents misinterpretations of experimental data, and the possibility to introduce chemical handles provides means for easier localization and detection.
32617953	5	36	theme	oligosaccharides	714:729	arg1	synthesis					701:709	the automated synthesis	687:709	the automated synthesis of oligosaccharides	687:729	In this chapter, detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays are described.
32617953	1	37	dep	structure	152:160	arg1	the					148:150	the	148:150	the	148:150	Synthetic cell wall oligosaccharides are promising molecular tools for investigating the structure and function of plant cell walls.
32617953	2	38	theme	well-defined	202:213	arg1	structure					215:223	well-defined structure	202:223	well-defined structure	202:223	Their well-defined structure and high purity prevents misinterpretations of experimental data, and the possibility to introduce chemical handles provides means for easier localization and detection.
32617953	2	39	theme	data	285:288	arg1	misinterpretations					250:267	misinterpretations	250:267	misinterpretations of experimental data	250:288	Their well-defined structure and high purity prevents misinterpretations of experimental data, and the possibility to introduce chemical handles provides means for easier localization and detection.
32617953	2	40	theme	experimental	272:283	arg1	data					285:288	experimental data	272:288	experimental data	272:288	Their well-defined structure and high purity prevents misinterpretations of experimental data, and the possibility to introduce chemical handles provides means for easier localization and detection.
32617953	3	41	theme	efficient	466:474	arg1	preparation					476:486	the efficient preparation	462:486	the efficient preparation of oligosaccharide libraries	462:515	Automated glycan assembly as emerged has a powerful new method for the efficient preparation of oligosaccharide libraries.
32617953	5	42	theme	biological	757:766	arg1	assays					768:773	biological assays	757:773	biological assays	757:773	In this chapter, detailed experimental procedures for the automated synthesis of oligosaccharides that are ready for use in biological assays are described.
34331854	5	0	theme	diazirine-modified	720:737	arg1	GlcNAc					739:744	diazirine-modified GlcNAc	720:744	diazirine-modified GlcNAc	720:744	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	0	1	theme	partners	94:101	arg1	capture					53:59	covalent capture	44:59	covalent capture of N-linked glycoprotein-binding partners on the cell surface	44:121	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	6	2	theme	cross-linking	901:913	arg1	extent					891:896	The extent	887:896	The extent of cross-linking	887:913	The extent of cross-linking correlates with display of the preferred glycan ligands for the GBPs.
34331854	2	3	theme	binding	395:401	arg1	affinities					403:412	low binding affinities	391:412	low binding affinities	391:412	Biochemical identification and characterization of glycan-mediated interactions is often made difficult by low binding affinities.
34331854	0	4	theme	cell	110:113	arg1	surface					115:121	the cell surface	106:121	the cell surface	106:121	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	7	5	theme	protein	1055:1061	arg1	components					1063:1072	protein components	1055:1072	protein components of cross-linked N-linked glycoproteins	1055:1111	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	4	6	theme	modest	665:670	arg1	perturbations					672:684	modest perturbations	665:684	modest perturbations to glycan structure	665:704	We characterize sites at which diazirine-modified GlcNAc is incorporated, as well as modest perturbations to glycan structure.
34331854	8	7	from	characterization	1200:1215	arg1	useful					1172:1177	useful	1172:1177	useful	1172:1177	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	5	8	theme	cholera	822:828	arg1	B					844:844	cholera toxin subunit B	822:844	cholera toxin subunit B	822:844	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	5	8	theme	cholera	822:828	arg1	GBPs					801:804	two extracellular GBPs	783:804	two extracellular GBPs	783:804	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	0	9	from	capture	53:59	arg1	surface					115:121	the cell surface	106:121	the cell surface	106:121	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	3	10	theme	photo-cross-linker	474:491	arg1	introduction					446:457	the metabolic introduction	432:457	the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces	432:577	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	3	11	theme	N-acetylglucosamine	498:516	arg1	residues					527:534	N-acetylglucosamine (GlcNAc) residues	498:534	N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces	498:577	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	3	11	theme	N-acetylglucosamine	498:516	arg1	glycoproteins					548:560	N-linked glycoproteins	539:560	N-linked glycoproteins	539:560	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	5	12	theme	toxin	830:834	arg1	B					844:844	cholera toxin subunit B	822:844	cholera toxin subunit B	822:844	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	5	12	theme	toxin	830:834	arg1	GBPs					801:804	two extracellular GBPs	783:804	two extracellular GBPs	783:804	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	5	13	theme	cell-surface	850:861	arg1	glycoproteins					872:884	cell-surface N-linked glycoproteins	850:884	cell-surface N-linked glycoproteins	850:884	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	8	14	from	discovery	1186:1194	arg1	useful					1172:1177	useful	1172:1177	useful	1172:1177	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	0	15	theme	photo-cross-linking	2:20	arg1	analog					29:34	A photo-cross-linking GlcNAc analog	0:34	A photo-cross-linking GlcNAc analog	0:34	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	5	16	theme	subunit	836:842	arg1	B					844:844	cholera toxin subunit B	822:844	cholera toxin subunit B	822:844	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	5	16	theme	subunit	836:842	arg1	GBPs					801:804	two extracellular GBPs	783:804	two extracellular GBPs	783:804	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	1	17	theme	direct	191:196	arg1	interactions					206:217	direct binding interactions	191:217	direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs)	191:281	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	3	18	theme	metabolic	436:444	arg1	introduction					446:457	the metabolic introduction	432:457	the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces	432:577	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	7	19	theme	cross-linked	1009:1020	arg1	complexes					1022:1030	covalently cross-linked complexes	998:1030	covalently cross-linked complexes	998:1030	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	1	20	theme	binding	198:204	arg1	interactions					206:217	direct binding interactions	191:217	direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs)	191:281	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	2	21	theme	interactions	351:362	arg1	characterization					315:330	characterization	315:330	characterization	315:330	Biochemical identification and characterization of glycan-mediated interactions is often made difficult by low binding affinities.
34331854	2	21	theme	interactions	351:362	arg1	identification					296:309	identification	296:309	identification	296:309	Biochemical identification and characterization of glycan-mediated interactions is often made difficult by low binding affinities.
34331854	8	22	dep	discovery	1186:1194	arg1	the					1182:1184	the	1182:1184	the	1182:1184	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	0	23	theme	GlcNAc	22:27	arg1	analog					29:34	A photo-cross-linking GlcNAc analog	0:34	A photo-cross-linking GlcNAc analog	0:34	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	7	24	link	cross-linked	1077:1088	arg1	glycoproteins					1099:1111	cross-linked N-linked glycoproteins	1077:1111	cross-linked N-linked glycoproteins	1077:1111	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	5	25	theme	extracellular	787:799	arg1	B					844:844	cholera toxin subunit B	822:844	cholera toxin subunit B	822:844	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	5	25	theme	extracellular	787:799	arg1	galectin-1					807:816	galectin-1	807:816	galectin-1	807:816	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	5	25	theme	extracellular	787:799	arg1	GBPs					801:804	two extracellular GBPs	783:804	two extracellular GBPs	783:804	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	6	26	theme	ligands	963:969	arg1	display					931:937	display	931:937	display of the preferred glycan ligands for the GBPs	931:982	The extent of cross-linking correlates with display of the preferred glycan ligands for the GBPs.
34331854	2	27	theme	glycan-mediated	335:349	arg1	interactions					351:362	glycan-mediated interactions	335:362	glycan-mediated interactions	335:362	Biochemical identification and characterization of glycan-mediated interactions is often made difficult by low binding affinities.
34331854	0	28	theme	covalent	44:51	arg1	capture					53:59	covalent capture	44:59	covalent capture of N-linked glycoprotein-binding partners on the cell surface	44:121	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	7	29	link	N-linked	1090:1097	arg1	glycoproteins					1099:1111	cross-linked N-linked glycoproteins	1077:1111	cross-linked N-linked glycoproteins	1077:1111	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	1	30	with	interactions	206:217	arg1	proteins					267:274	glycan-binding proteins	252:274	membrane-bound and secreted glycan-binding proteins (GBPs)	224:281	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	1	30	with	interactions	206:217	arg1	GBPs					277:280	GBPs	277:280	GBPs	277:280	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	6	31	theme	glycan	956:961	arg1	ligands					963:969	the preferred glycan ligands	942:969	the preferred glycan ligands for the GBPs	942:982	The extent of cross-linking correlates with display of the preferred glycan ligands for the GBPs.
34331854	1	32	theme	membrane-bound	224:237	arg1	proteins					267:274	glycan-binding proteins	252:274	membrane-bound and secreted glycan-binding proteins (GBPs)	224:281	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	1	32	theme	membrane-bound	224:237	arg1	GBPs					277:280	GBPs	277:280	GBPs	277:280	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	3	33	theme	diazirine	464:472	arg1	photo-cross-linker					474:491	a diazirine photo-cross-linker	462:491	a diazirine photo-cross-linker	462:491	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	8	34	from	useful	1172:1177	arg1	discovery					1186:1194	discovery	1186:1194	discovery	1186:1194	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	8	34	from	useful	1172:1177	arg1	characterization					1200:1215	characterization	1200:1215	characterization	1200:1215	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	5	35	theme	N-linked	863:870	arg1	glycoproteins					872:884	cell-surface N-linked glycoproteins	850:884	cell-surface N-linked glycoproteins	850:884	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	6	36	theme	preferred	946:954	arg1	ligands					963:969	the preferred glycan ligands	942:969	the preferred glycan ligands for the GBPs	942:982	The extent of cross-linking correlates with display of the preferred glycan ligands for the GBPs.
34331854	7	37	gly	glycoproteins	1099:1111	arg1	glycoproteins					1099:1111	cross-linked N-linked glycoproteins	1077:1111	cross-linked N-linked glycoproteins	1077:1111	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	3	38	link	N-linked	539:546	arg1	glycoproteins					548:560	N-linked glycoproteins	539:560	N-linked glycoproteins	539:560	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	7	39	theme	glycoproteins	1099:1111	arg1	components					1063:1072	protein components	1055:1072	protein components of cross-linked N-linked glycoproteins	1055:1111	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	2	40	theme	low	391:393	arg1	affinities					403:412	low binding affinities	391:412	low binding affinities	391:412	Biochemical identification and characterization of glycan-mediated interactions is often made difficult by low binding affinities.
34331854	4	41	theme	diazirine-modified	611:628	arg1	GlcNAc					630:635	diazirine-modified GlcNAc	611:635	diazirine-modified GlcNAc	611:635	We characterize sites at which diazirine-modified GlcNAc is incorporated, as well as modest perturbations to glycan structure.
34331854	5	42	link	N-linked	863:870	arg1	glycoproteins					872:884	cell-surface N-linked glycoproteins	850:884	cell-surface N-linked glycoproteins	850:884	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	3	43	from	residues	527:534	arg1	surfaces					570:577	cell surfaces	565:577	cell surfaces	565:577	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	3	44	theme	cell	565:568	arg1	surfaces					570:577	cell surfaces	565:577	cell surfaces	565:577	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	5	45	gly	glycoproteins	872:884	arg1	glycoproteins					872:884	cell-surface N-linked glycoproteins	850:884	cell-surface N-linked glycoproteins	850:884	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	7	46	theme	proteomics	1132:1141	arg1	analysis					1143:1150	proteomics analysis	1132:1150	proteomics analysis	1132:1150	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	2	47	theme	Biochemical	284:294	arg1	identification					296:309	identification	296:309	identification	296:309	Biochemical identification and characterization of glycan-mediated interactions is often made difficult by low binding affinities.
34331854	0	48	link	N-linked	64:71	arg1	partners					94:101	N-linked glycoprotein-binding partners	64:101	N-linked glycoprotein-binding partners	64:101	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	3	49	theme	N-linked	539:546	arg1	glycoproteins					548:560	N-linked glycoproteins	539:560	N-linked glycoproteins	539:560	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	3	50	gly	glycoproteins	548:560	arg1	glycoproteins					548:560	N-linked glycoproteins	539:560	N-linked glycoproteins	539:560	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	1	51	theme	secreted	243:250	arg1	proteins					267:274	glycan-binding proteins	252:274	membrane-bound and secreted glycan-binding proteins (GBPs)	224:281	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	1	51	theme	secreted	243:250	arg1	GBPs					277:280	GBPs	277:280	GBPs	277:280	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	8	52	theme	binding	1220:1226	arg1	interactions					1228:1239	binding interactions	1220:1239	binding interactions that depend on N-glycans	1220:1264	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	7	53	theme	cross-linked	1077:1088	arg1	glycoproteins					1099:1111	cross-linked N-linked glycoproteins	1077:1111	cross-linked N-linked glycoproteins	1077:1111	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	3	54	theme	glycoproteins	548:560	arg1	residues					527:534	N-acetylglucosamine (GlcNAc) residues	498:534	N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces	498:577	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	3	54	theme	glycoproteins	548:560	arg1	glycoproteins					548:560	N-linked glycoproteins	539:560	N-linked glycoproteins	539:560	Here we describe the metabolic introduction of a diazirine photo-cross-linker onto N-acetylglucosamine (GlcNAc) residues of N-linked glycoproteins on cell surfaces.
34331854	1	55	theme	glycan-binding	252:265	arg1	proteins					267:274	glycan-binding proteins	252:274	membrane-bound and secreted glycan-binding proteins (GBPs)	224:281	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	1	55	theme	glycan-binding	252:265	arg1	GBPs					277:280	GBPs	277:280	GBPs	277:280	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	0	56	theme	glycoprotein-binding	73:92	arg1	partners					94:101	N-linked glycoprotein-binding partners	64:101	N-linked glycoprotein-binding partners	64:101	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	8	57	theme	interactions	1228:1239	arg1	discovery					1186:1194	discovery	1186:1194	discovery	1186:1194	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	8	57	theme	interactions	1228:1239	arg1	characterization					1200:1215	characterization	1200:1215	characterization	1200:1215	This method may be useful in the discovery and characterization of binding interactions that depend on N-glycans.
34331854	7	58	theme	N-linked	1090:1097	arg1	glycoproteins					1099:1111	cross-linked N-linked glycoproteins	1077:1111	cross-linked N-linked glycoproteins	1077:1111	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	1	59	theme	cell-surface	151:162	arg1	proteins					164:171	cell-surface proteins	151:171	cell-surface proteins	151:171	N-glycans are displayed on cell-surface proteins and can engage in direct binding interactions with membrane-bound and secreted glycan-binding proteins (GBPs).
34331854	0	60	theme	N-linked	64:71	arg1	partners					94:101	N-linked glycoprotein-binding partners	64:101	N-linked glycoprotein-binding partners	64:101	A photo-cross-linking GlcNAc analog enables covalent capture of N-linked glycoprotein-binding partners on the cell surface.
34331854	5	61	used	used	753:756	arg2	GlcNAc					739:744	diazirine-modified GlcNAc	720:744	diazirine-modified GlcNAc	720:744	We show that diazirine-modified GlcNAc can be used to covalently cross-link two extracellular GBPs, galectin-1 and cholera toxin subunit B, to cell-surface N-linked glycoproteins.
34331854	7	62	link	cross-linked	1009:1020	arg1	complexes					1022:1030	covalently cross-linked complexes	998:1030	covalently cross-linked complexes	998:1030	In addition, covalently cross-linked complexes could be isolated, and protein components of cross-linked N-linked glycoproteins were identified by proteomics analysis.
34331854	4	63	theme	glycan	689:694	arg1	structure					696:704	glycan structure	689:704	glycan structure	689:704	We characterize sites at which diazirine-modified GlcNAc is incorporated, as well as modest perturbations to glycan structure.
34404781	5	0	theme	glycoprofiles	774:786	arg1	comparison					750:759	direct comparison	743:759	direct comparison of different glycoprofiles	743:786	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	0	1	from	sparsity	15:22	arg1	glycomics					47:55	glycomics	47:55	glycomics	47:55	Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis.
34404781	8	2	theme	oligosaccharide	1115:1129	arg1	profiles					1131:1138	human milk oligosaccharide profiles	1104:1138	human milk oligosaccharide profiles	1104:1138	We further analyze human milk oligosaccharide profiles and find mother's fucosyltransferase-dependent secretor-status indirectly impact the sialylation.
34404781	7	3	theme	tetra-antennary	1057:1071	arg1	structures					1073:1082	tetra-antennary structures	1057:1082	tetra-antennary structures	1057:1082	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	1	4	theme	many	158:161	arg1	functions					174:182	many organismal functions	158:182	many organismal functions	158:182	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	7	5	theme	meaningful	934:943	arg1	clustering					945:954	biologically meaningful clustering	921:954	biologically meaningful clustering of mutant cell glycoprofiles	921:983	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	2	6	from	Advances	185:192	arg1	glycomics					197:205	glycomics	197:205	glycomics	197:205	Advances in glycomics are elucidating the essential roles of glycans.
34404781	5	7	theme	measured	653:660	arg1	glycans					662:668	all measured glycans	649:668	all measured glycans	649:668	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	7	8	theme	fucosyltransferase	1027:1044	arg1	mutants					1046:1052	fucosyltransferase mutants	1027:1052	fucosyltransferase mutants	1027:1052	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	1	9	theme	organismal	163:172	arg1	functions					174:182	many organismal functions	158:182	many organismal functions	158:182	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	4	10	dep	the	463:465	arg1	overlap					467:473	overlap	467:473	overlap	467:473	Furthermore, the overlap of measured glycans can be low across samples.
34404781	3	11	theme	glycan	359:364	arg1	dependent					369:377	dependent	369:377	dependent	369:377	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	3	11	theme	glycan	359:364	arg1	abundance					341:349	the abundance	337:349	the abundance of each glycan	337:364	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	7	12	theme	knockout-specific	998:1014	arg1	effects					1016:1022	knockout-specific effects	998:1022	knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures	998:1082	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	10	13	theme	glycomics	1533:1541	arg1	data					1543:1546	glycomics data	1533:1546	glycomics data	1533:1546	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	7	14	theme	mutants	1046:1052	arg1	effects					1016:1022	knockout-specific effects	998:1022	knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures	998:1082	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	10	15	theme	power	1515:1519	arg1	advantage					1490:1498	full advantage	1485:1498	full advantage of the growing power and size of glycomics data	1485:1546	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	5	16	from	non-independence	698:713	arg1	glycomics					718:726	glycomics	718:726	glycomics	718:726	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	4	17	theme	measured	478:485	arg1	glycans					487:493	measured glycans	478:493	measured glycans	478:493	Furthermore, the overlap of measured glycans can be low across samples.
34404781	10	18	theme	data	1543:1546	arg1	size					1525:1528	size	1525:1528	size	1525:1528	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	10	18	theme	data	1543:1546	arg1	power					1515:1519	the growing power	1503:1519	the growing power	1503:1519	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	5	19	with	challenges	539:548	arg1	GlyCompare					555:564	GlyCompare	555:564	GlyCompare	555:564	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	5	19	with	challenges	539:548	arg1	approach					592:599	a glycomic data analysis approach	567:599	a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics	567:726	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	5	20	theme	direct	743:748	arg1	comparison					750:759	direct comparison	743:759	direct comparison of different glycoprofiles	743:786	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	5	21	theme	shared	619:624	arg1	steps					639:643	shared biosynthetic steps	619:643	shared biosynthetic steps for all measured glycans	619:668	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	9	22	theme	site-specific	1310:1322	arg1	data					1352:1355	site-specific compositional glycosylation data	1310:1355	site-specific compositional glycosylation data	1310:1355	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	5	23	theme	biosynthetic	626:637	arg1	steps					639:643	shared biosynthetic steps	619:643	shared biosynthetic steps for all measured glycans	619:668	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	9	24	theme	compositional	1324:1336	arg1	data					1352:1355	site-specific compositional glycosylation data	1310:1355	site-specific compositional glycosylation data	1310:1355	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	3	25	theme	many	382:385	arg1	glycans					393:399	many other glycans	382:399	many other glycans that share many intermediate biosynthetic steps	382:447	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	0	26	from	interdependence	28:42	arg1	glycomics					47:55	glycomics	47:55	glycomics	47:55	Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis.
34404781	8	27	theme	fucosyltransferase-dependent	1158:1185	arg1	secretor-status					1187:1201	mother's fucosyltransferase-dependent secretor-status	1149:1201	mother's fucosyltransferase-dependent secretor-status indirectly impact the sialylation	1149:1235	We further analyze human milk oligosaccharide profiles and find mother's fucosyltransferase-dependent secretor-status indirectly impact the sialylation.
34404781	5	28	theme	glycomic	569:576	arg1	GlyCompare					555:564	GlyCompare	555:564	GlyCompare	555:564	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	5	28	theme	glycomic	569:576	arg1	approach					592:599	a glycomic data analysis approach	567:599	a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics	567:726	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	10	29	theme	substructure-oriented	1422:1442	arg1	approach					1444:1451	Our substructure-oriented approach	1418:1451	Our substructure-oriented approach	1418:1451	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	3	30	theme	intermediate	417:428	arg1	steps					443:447	many intermediate biosynthetic steps	412:447	many intermediate biosynthetic steps	412:447	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	3	31	theme	other	387:391	arg1	glycans					393:399	many other glycans	382:399	many other glycans that share many intermediate biosynthetic steps	382:447	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	5	32	theme	data	578:581	arg1	GlyCompare					555:564	GlyCompare	555:564	GlyCompare	555:564	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	5	32	theme	data	578:581	arg1	approach					592:599	a glycomic data analysis approach	567:599	a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics	567:726	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	9	33	theme	glycosylation	1338:1350	arg1	data					1352:1355	site-specific compositional glycosylation data	1310:1355	site-specific compositional glycosylation data	1310:1355	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	3	34	theme	biosynthetic	430:441	arg1	steps					443:447	many intermediate biosynthetic steps	412:447	many intermediate biosynthetic steps	412:447	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	7	35	theme	glycoprofiles	971:983	arg1	clustering					945:954	biologically meaningful clustering	921:954	biologically meaningful clustering of mutant cell glycoprofiles	921:983	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	5	36	theme	analysis	583:590	arg1	GlyCompare					555:564	GlyCompare	555:564	GlyCompare	555:564	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	5	36	theme	analysis	583:590	arg1	approach					592:599	a glycomic data analysis approach	567:599	a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics	567:726	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	6	37	from	erythropoietin	895:908	arg1	profiles					865:872	diverse N-glycan profiles	848:872	diverse N-glycan profiles from glycoengineered erythropoietin	848:908	Using GlyCompare, we study diverse N-glycan profiles from glycoengineered erythropoietin.
34404781	1	38	theme	fundamental	108:118	arg1	blocks					138:143	fundamental cellular building blocks	108:143	fundamental cellular building blocks	108:143	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	1	38	theme	fundamental	108:118	arg1	Glycans					96:102	Glycans	96:102	Glycans	96:102	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	9	39	from	method	1260:1265	arg1	O-glycans					1281:1289	mucin-type O-glycans	1270:1289	mucin-type O-glycans	1270:1289	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	9	39	from	method	1260:1265	arg1	gangliosides					1292:1303	gangliosides	1292:1303	gangliosides	1292:1303	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	9	39	from	method	1260:1265	arg1	data					1352:1355	site-specific compositional glycosylation data	1310:1355	site-specific compositional glycosylation data	1310:1355	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	2	40	theme	glycans	246:252	arg1	roles					237:241	the essential roles	223:241	the essential roles of glycans	223:252	Advances in glycomics are elucidating the essential roles of glycans.
34404781	3	41	theme	many	412:415	arg1	steps					443:447	many intermediate biosynthetic steps	412:447	many intermediate biosynthetic steps	412:447	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	5	42	theme	statistical	802:812	arg1	power					814:818	statistical power	802:818	statistical power	802:818	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	6	43	theme	glycoengineered	879:893	arg1	erythropoietin					895:908	glycoengineered erythropoietin	879:908	glycoengineered erythropoietin	879:908	Using GlyCompare, we study diverse N-glycan profiles from glycoengineered erythropoietin.
34404781	10	44	theme	growing	1507:1513	arg1	power					1515:1519	the growing power	1503:1519	the growing power	1503:1519	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	3	45	theme	glycomics	311:319	arg1	datasets					321:328	large glycomics datasets	305:328	large glycomics datasets	305:328	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	9	46	theme	disease-specific	1379:1394	arg1	presentations					1403:1415	disease-specific glycan presentations	1379:1415	disease-specific glycan presentations	1379:1415	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	1	47	theme	cellular	120:127	arg1	blocks					138:143	fundamental cellular building blocks	108:143	fundamental cellular building blocks	108:143	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	1	47	theme	cellular	120:127	arg1	Glycans					96:102	Glycans	96:102	Glycans	96:102	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	8	48	dep	secretor-status	1187:1201	arg1	impact					1214:1219	impact	1214:1219	impact	1214:1219	We further analyze human milk oligosaccharide profiles and find mother's fucosyltransferase-dependent secretor-status indirectly impact the sialylation.
34404781	9	49	theme	glycan	1396:1401	arg1	presentations					1403:1415	disease-specific glycan presentations	1379:1415	disease-specific glycan presentations	1379:1415	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	2	50	theme	essential	227:235	arg1	roles					237:241	the essential roles	223:241	the essential roles of glycans	223:252	Advances in glycomics are elucidating the essential roles of glycans.
34404781	1	51	theme	building	129:136	arg1	blocks					138:143	fundamental cellular building blocks	108:143	fundamental cellular building blocks	108:143	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	1	51	theme	building	129:136	arg1	Glycans					96:102	Glycans	96:102	Glycans	96:102	Glycans are fundamental cellular building blocks, involved in many organismal functions.
34404781	7	52	theme	mutant	959:964	arg1	glycoprofiles					971:983	mutant cell glycoprofiles	959:983	mutant cell glycoprofiles	959:983	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	6	53	theme	N-glycan	856:863	arg1	profiles					865:872	diverse N-glycan profiles	848:872	diverse N-glycan profiles from glycoengineered erythropoietin	848:908	Using GlyCompare, we study diverse N-glycan profiles from glycoengineered erythropoietin.
34404781	10	54	theme	full	1485:1488	arg1	advantage					1490:1498	full advantage	1485:1498	full advantage of the growing power and size of glycomics data	1485:1546	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	7	55	theme	cell	966:969	arg1	glycoprofiles					971:983	mutant cell glycoprofiles	959:983	mutant cell glycoprofiles	959:983	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	5	56	from	sparsity	685:692	arg1	glycomics					718:726	glycomics	718:726	glycomics	718:726	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	3	57	theme	large	305:309	arg1	datasets					321:328	large glycomics datasets	305:328	large glycomics datasets	305:328	Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.
34404781	6	58	theme	diverse	848:854	arg1	profiles					865:872	diverse N-glycan profiles	848:872	diverse N-glycan profiles from glycoengineered erythropoietin	848:908	Using GlyCompare, we study diverse N-glycan profiles from glycoengineered erythropoietin.
34404781	8	59	theme	human	1104:1108	arg1	profiles					1131:1138	human milk oligosaccharide profiles	1104:1138	human milk oligosaccharide profiles	1104:1138	We further analyze human milk oligosaccharide profiles and find mother's fucosyltransferase-dependent secretor-status indirectly impact the sialylation.
34404781	10	60	theme	size	1525:1528	arg1	advantage					1490:1498	full advantage	1485:1498	full advantage of the growing power and size of glycomics data	1485:1546	Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
34404781	9	61	theme	mucin-type	1270:1279	arg1	O-glycans					1281:1289	mucin-type O-glycans	1270:1289	mucin-type O-glycans	1270:1289	Finally, we apply our method on mucin-type O-glycans, gangliosides, and site-specific compositional glycosylation data to reveal tissues and disease-specific glycan presentations.
34404781	7	62	from	effects	1016:1022	arg1	structures					1073:1082	tetra-antennary structures	1057:1082	tetra-antennary structures	1057:1082	We obtain biologically meaningful clustering of mutant cell glycoprofiles and identify knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures.
34404781	8	63	theme	milk	1110:1113	arg1	profiles					1131:1138	human milk oligosaccharide profiles	1104:1138	human milk oligosaccharide profiles	1104:1138	We further analyze human milk oligosaccharide profiles and find mother's fucosyltransferase-dependent secretor-status indirectly impact the sialylation.
34404781	5	64	theme	different	764:772	arg1	glycoprofiles					774:786	different glycoprofiles	764:786	different glycoprofiles	764:786	We address these challenges with GlyCompare, a glycomic data analysis approach that accounts for shared biosynthetic steps for all measured glycans to correct for sparsity and non-independence in glycomics, which enables direct comparison of different glycoprofiles and increases statistical power.
34404781	0	65	theme	glycan	75:80	arg1	biosynthesis					82:93	glycan biosynthesis	75:93	glycan biosynthesis	75:93	Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis.
33045166	1	0	theme	chemical	192:199	arg1	synthesis					201:209	an efficient chemical synthesis	179:209	an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	179:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	0	1	theme	Convergent	91:100	arg1	Glycosylation					102:114	Stereoselective Convergent Glycosylation	75:114	Stereoselective Convergent Glycosylation	75:114	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	3	2	theme	function	840:847	arg1	examination					808:818	the examination	804:818	the examination of their biological function	804:847	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	0	3	theme	Chemoselective	120:133	arg1	Aspartylation					147:159	Chemoselective Solid-Phase Aspartylation	120:159	Chemoselective Solid-Phase Aspartylation	120:159	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	1	4	link	N-linked	243:250	arg1	glycopeptides					252:264	homogeneous human E-cadherin N-linked glycopeptides	214:264	homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	214:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	5	theme	Asn-633	320:326	arg1	site					344:347	the Asn-633 N-glycosylation site	316:347	the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	316:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	6	theme	core-fucosylated	429:444	arg1	tetrasaccharide					446:460	a core-fucosylated tetrasaccharide	427:460	a core-fucosylated tetrasaccharide	427:460	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	7	theme	N-glycosylation	328:342	arg1	site					344:347	the Asn-633 N-glycosylation site	316:347	the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	316:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	2	8	theme	glycosyl	649:656	arg1	fluororide					658:667	glycosyl fluororide	649:667	glycosyl fluororide	649:667	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	2	8	theme	glycosyl	649:656	arg1	donor					674:678	a donor	672:678	a donor	672:678	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	1	9	gly	glycopeptides	252:264	arg2	glycopeptides					252:264	homogeneous human E-cadherin N-linked glycopeptides	214:264	homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	214:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	2	10	theme	key	514:516	arg1	aspartylation					554:566	a chemoselective on-resin aspartylation	528:566	a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor	528:678	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	2	10	theme	key	514:516	arg1	steps					518:522	The key steps	510:522	The key steps	510:522	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	0	11	theme	Solid-Phase	135:145	arg1	Aspartylation					147:159	Chemoselective Solid-Phase Aspartylation	120:159	Chemoselective Solid-Phase Aspartylation	120:159	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	2	12	theme	pseudoproline-containing	576:599	arg1	peptide					601:607	a pseudoproline-containing peptide	574:607	a pseudoproline-containing peptide	574:607	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	2	13	theme	chemoselective	530:543	arg1	aspartylation					554:566	a chemoselective on-resin aspartylation	528:566	a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor	528:678	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	2	13	theme	chemoselective	530:543	arg1	steps					518:522	The key steps	510:522	The key steps	510:522	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	1	14	theme	homogeneous	214:224	arg1	glycopeptides					252:264	homogeneous human E-cadherin N-linked glycopeptides	214:264	homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	214:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	2	15	theme	on-resin	545:552	arg1	aspartylation					554:566	a chemoselective on-resin aspartylation	528:566	a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor	528:678	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	2	15	theme	on-resin	545:552	arg1	steps					518:522	The key steps	510:522	The key steps	510:522	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	3	16	gly	glycopeptides	786:798	arg2	glycopeptides					786:798	homogeneous N-linked glycopeptides	765:798	homogeneous N-linked glycopeptides	765:798	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	1	17	theme	human	226:230	arg1	glycopeptides					252:264	homogeneous human E-cadherin N-linked glycopeptides	214:264	homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	214:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	0	18	theme	Chemical	0:7	arg1	Synthesis					9:17	Chemical Synthesis	0:17	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.	0:160	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	1	19	gly	N-glycosylation	328:342	arg2	site					344:347	the Asn-633 N-glycosylation site	316:347	the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	316:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	3	20	theme	potential	718:726	arg1	utility					728:734	potential utility	718:734	potential utility	718:734	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	0	21	theme	Homogeneous	22:32	arg1	Glycopeptides					60:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	1	22	with	site	344:347	arg1	tetrasaccharide					446:460	a core-fucosylated tetrasaccharide	427:460	a core-fucosylated tetrasaccharide	427:460	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	22	with	site	344:347	arg1	octasaccharide					494:507	a complex-type biantennary octasaccharide	467:507	a complex-type biantennary octasaccharide	467:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	22	with	site	344:347	arg1	trisaccharide					412:424	a conserved trisaccharide	400:424	a conserved trisaccharide	400:424	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	22	with	site	344:347	arg1	structures					378:387	representative N-glycan structures	354:387	representative N-glycan structures	354:387	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	3	23	theme	synthetic	686:694	arg1	strategy					696:703	This synthetic strategy	681:703	This synthetic strategy	681:703	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	1	24	gly	core-fucosylated	429:444	arg1	tetrasaccharide					446:460	a core-fucosylated tetrasaccharide	427:460	a core-fucosylated tetrasaccharide	427:460	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	25	theme	N-linked	243:250	arg1	glycopeptides					252:264	homogeneous human E-cadherin N-linked glycopeptides	214:264	homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	214:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	26	theme	representative	354:367	arg1	tetrasaccharide					446:460	a core-fucosylated tetrasaccharide	427:460	a core-fucosylated tetrasaccharide	427:460	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	26	theme	representative	354:367	arg1	octasaccharide					494:507	a complex-type biantennary octasaccharide	467:507	a complex-type biantennary octasaccharide	467:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	26	theme	representative	354:367	arg1	trisaccharide					412:424	a conserved trisaccharide	400:424	a conserved trisaccharide	400:424	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	26	theme	representative	354:367	arg1	structures					378:387	representative N-glycan structures	354:387	representative N-glycan structures	354:387	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	27	theme	glycopeptides	252:264	arg1	synthesis					201:209	an efficient chemical synthesis	179:209	an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	179:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	0	28	theme	E-Cadherin	40:49	arg1	Glycopeptides					60:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	1	29	theme	N-glycan	369:376	arg1	tetrasaccharide					446:460	a core-fucosylated tetrasaccharide	427:460	a core-fucosylated tetrasaccharide	427:460	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	29	theme	N-glycan	369:376	arg1	octasaccharide					494:507	a complex-type biantennary octasaccharide	467:507	a complex-type biantennary octasaccharide	467:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	29	theme	N-glycan	369:376	arg1	trisaccharide					412:424	a conserved trisaccharide	400:424	a conserved trisaccharide	400:424	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	29	theme	N-glycan	369:376	arg1	structures					378:387	representative N-glycan structures	354:387	representative N-glycan structures	354:387	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	30	theme	complex-type	469:480	arg1	octasaccharide					494:507	a complex-type biantennary octasaccharide	467:507	a complex-type biantennary octasaccharide	467:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	0	31	theme	Human	34:38	arg1	Glycopeptides					60:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	1	32	theme	biantennary	482:492	arg1	octasaccharide					494:507	a complex-type biantennary octasaccharide	467:507	a complex-type biantennary octasaccharide	467:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	0	33	theme	Glycopeptides	60:72	arg1	Synthesis					9:17	Chemical Synthesis	0:17	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.	0:160	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	3	34	theme	glycopeptides	786:798	arg1	range					756:760	a wide range	749:760	a wide range of homogeneous N-linked glycopeptides	749:798	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	0	35	theme	N-Linked	51:58	arg1	Glycopeptides					60:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Homogeneous Human E-Cadherin N-Linked Glycopeptides	22:72	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	3	36	theme	N-linked	777:784	arg1	glycopeptides					786:798	homogeneous N-linked glycopeptides	765:798	homogeneous N-linked glycopeptides	765:798	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	3	37	theme	biological	829:838	arg1	function					840:847	their biological function	823:847	their biological function	823:847	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	3	38	theme	wide	751:754	arg1	range					756:760	a wide range	749:760	a wide range of homogeneous N-linked glycopeptides	749:798	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	3	39	theme	homogeneous	765:775	arg1	glycopeptides					786:798	homogeneous N-linked glycopeptides	765:798	homogeneous N-linked glycopeptides	765:798	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	1	40	theme	heptapeptide	282:293	arg1	sequence					295:302	a heptapeptide sequence	280:302	a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	280:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	0	41	theme	Stereoselective	75:89	arg1	Glycosylation					102:114	Stereoselective Convergent Glycosylation	75:114	Stereoselective Convergent Glycosylation	75:114	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	0	42	dep	Synthesis	9:17	arg1	Glycosylation					102:114	Stereoselective Convergent Glycosylation	75:114	Stereoselective Convergent Glycosylation	75:114	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	0	42	dep	Synthesis	9:17	arg1	Aspartylation					147:159	Chemoselective Solid-Phase Aspartylation	120:159	Chemoselective Solid-Phase Aspartylation	120:159	Chemical Synthesis of Homogeneous Human E-Cadherin N-Linked Glycopeptides: Stereoselective Convergent Glycosylation and Chemoselective Solid-Phase Aspartylation.
33045166	2	43	theme	stereoselective	613:627	arg1	glycosylation					629:641	stereoselective glycosylation	613:641	stereoselective glycosylation	613:641	The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor.
33045166	1	44	theme	conserved	402:410	arg1	trisaccharide					412:424	a conserved trisaccharide	400:424	a conserved trisaccharide	400:424	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	1	45	theme	efficient	182:190	arg1	synthesis					201:209	an efficient chemical synthesis	179:209	an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	179:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
33045166	3	46	link	N-linked	777:784	arg1	glycopeptides					786:798	homogeneous N-linked glycopeptides	765:798	homogeneous N-linked glycopeptides	765:798	This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.
33045166	1	47	theme	adjacent	304:311	arg1	sequence					295:302	a heptapeptide sequence	280:302	a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide	280:507	We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide.
31972267	2	0	theme	present	626:632	arg1	glycans					618:624	the glycans	614:624	the glycans present in the normal human heart	614:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	9	1	theme	medicine	2149:2156	arg1	efforts					2158:2164	future regenerative medicine efforts	2129:2164	future regenerative medicine efforts	2129:2164	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	4	2	theme	cardiac	1058:1064	arg1	glycome					1066:1072	the cardiac glycome	1054:1072	the cardiac glycome containing 265 N- and O-glycans	1054:1104	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	9	3	theme	future	2129:2134	arg1	efforts					2158:2164	future regenerative medicine efforts	2129:2164	future regenerative medicine efforts	2129:2164	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	1	4	attach	attached	318:325	arg2	glycan-moiety					304:316	the glycan-moiety	300:316	the glycan-moiety attached to the protein	300:340	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	1	4	attach	attached	318:325	arg2	critical					345:352	critical	345:352	critical	345:352	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	1	4	attach	attached	318:325	arg1	protein					334:340	the protein	330:340	the protein	330:340	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	5	5	theme	same	1212:1215	arg1	pool					1217:1220	the same pool	1208:1220	the same pool of N-glycan structures	1208:1243	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	2	6	theme	human	648:652	arg1	heart					654:658	the normal human heart	637:658	the normal human heart	637:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	3	7	theme	liquid	717:722	arg1	chromatography					724:737	porous graphitized carbon liquid chromatography	691:737	porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS)	691:783	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	8	8	theme	current	1887:1893	arg1	profiling					1934:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	4	9	theme	first	1015:1019	arg1	libraries					1041:1049	the first reference structure libraries	1011:1049	the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans	1011:1104	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	1	10	theme	critical	213:220	arg1	roles					222:226	critical roles	213:226	critical roles	213:226	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	7	11	theme	N-glycan	1772:1779	arg1	structures					1781:1790	the N-glycan structures	1768:1790	the N-glycan structures	1768:1790	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	3	12	theme	mass	755:758	arg1	PGC-LC-MS					774:782	PGC-LC-MS	774:782	PGC-LC-MS	774:782	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	3	12	theme	mass	755:758	arg1	spectrometry					760:771	mass spectrometry	755:771	mass spectrometry (PGC-LC-MS)	755:783	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	2	13	contain	have	585:588	arg2	view					606:609	a comprehensive view	590:609	a comprehensive view of the glycans present in the normal human heart	590:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	2	13	contain	have	585:588	arg1	we					565:566	we	565:566	we	565:566	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	0	14	theme	glycan	162:167	arg1	phenotypes					169:178	cell-type and culture stage-specific glycan phenotypes	125:178	cell-type and culture stage-specific glycan phenotypes	125:178	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	1	15	from	structure	251:259	arg1	health					277:282	health	277:282	health	277:282	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	1	15	from	structure	251:259	arg1	disease					288:294	disease	288:294	disease	288:294	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	1	16	gly	glycoproteins	194:206	arg1	glycoproteins					194:206	Cell surface glycoproteins	181:206	Cell surface glycoproteins	181:206	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	9	17	theme	immunogenic	2206:2216	arg1	potential					2218:2226	the immunogenic potential	2202:2226	the immunogenic potential of hiPSC-CM	2202:2238	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	6	18	dep	in	1557:1558	arg1	vitro					1560:1564	vitro	1560:1564	vitro	1560:1564	Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughout in vitro differentiation were observed and differences between primary and hiPSC-CM were revealed.
31972267	8	19	theme	new	1955:1957	arg1	considerations					1959:1972	new considerations	1955:1972	new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing	1955:2082	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	7	20	theme	differentiation	1736:1750	arg1	time-points					1721:1731	these time-points	1715:1731	these time-points of differentiation	1715:1750	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	9	21	theme	primary	2318:2324	arg1	CM					2326:2327	adult primary CM	2312:2327	adult primary CM	2312:2327	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	3	22	theme	structure	804:812	arg1	libraries					814:822	glycan structure libraries	797:822	glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM)	797:981	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	1	23	theme	protein	365:371	arg1	folding					373:379	proper protein folding	358:379	proper protein folding	358:379	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	6	24	theme	in	1557:1558	arg1	differentiation					1566:1580	in vitro differentiation	1557:1580	in vitro differentiation	1557:1580	Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughout in vitro differentiation were observed and differences between primary and hiPSC-CM were revealed.
31972267	1	25	theme	Cell	181:184	arg1	glycoproteins					194:206	Cell surface glycoproteins	181:206	Cell surface glycoproteins	181:206	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	3	26	theme	tissue	848:853	arg1	homogenate					855:864	primary human heart tissue homogenate	828:864	primary human heart tissue homogenate	828:864	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	0	27	theme	stem	85:88	arg1	cardiomyocytes					103:116	pluripotent stem cell-derived cardiomyocytes	73:116	pluripotent stem cell-derived cardiomyocytes	73:116	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	3	28	theme	human	836:840	arg1	homogenate					855:864	primary human heart tissue homogenate	828:864	primary human heart tissue homogenate	828:864	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	2	29	theme	cardiac	545:551	arg1	biomarkers					553:562	cardiac biomarkers	545:562	cardiac biomarkers	545:562	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	5	30	located	detected	1249:1256	arg1	type					1273:1276	each sample type	1261:1276	each sample type	1261:1276	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	5	30	located	detected	1249:1256	arg2	pool					1217:1220	the same pool	1208:1220	the same pool of N-glycan structures	1208:1243	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	0	31	theme	cell-type	125:133	arg1	phenotypes					169:178	cell-type and culture stage-specific glycan phenotypes	125:178	cell-type and culture stage-specific glycan phenotypes	125:178	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	9	32	theme	hiPSC-CM	2231:2238	arg1	potential					2218:2226	the immunogenic potential	2202:2226	the immunogenic potential of hiPSC-CM	2202:2238	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	3	33	theme	heart	907:911	arg1	tissue					913:918	human heart tissue	901:918	human heart tissue	901:918	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	4	34	theme	reference	1021:1029	arg1	libraries					1041:1049	the first reference structure libraries	1011:1049	the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans	1011:1104	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	0	35	theme	Reference	0:8	arg1	libraries					27:35	Reference glycan structure libraries	0:35	Reference glycan structure libraries of primary human cardiomyocytes	0:67	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	3	36	theme	pluripotent	939:949	arg1	cell					956:959	human induced pluripotent stem cell	925:959	human induced pluripotent stem cell derived CM (hiPSC-CM)	925:981	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	8	37	theme	testing	2076:2082	arg1	studies					2028:2034	studies	2028:2034	studies of human development, disease, and drug testing	2028:2082	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	2	38	theme	glycan	451:456	arg1	structures					458:467	glycan structures	451:467	glycan structures	451:467	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	2	38	theme	glycan	451:456	arg1	modulators					477:486	key modulators	473:486	key modulators of heart function	473:504	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	0	39	theme	structure	17:25	arg1	libraries					27:35	Reference glycan structure libraries	0:35	Reference glycan structure libraries of primary human cardiomyocytes	0:67	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	5	40	theme	heart	1183:1187	arg1	homogenate					1196:1205	heart tissue homogenate	1183:1205	heart tissue homogenate	1183:1205	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	3	41	theme	human	925:929	arg1	cell					956:959	human induced pluripotent stem cell	925:959	human induced pluripotent stem cell derived CM (hiPSC-CM)	925:981	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	8	42	theme	development	2045:2055	arg1	studies					2028:2034	studies	2028:2034	studies of human development, disease, and drug testing	2028:2082	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	5	43	theme	primary	1151:1157	arg1	tissue					1165:1170	primary heart tissue	1151:1170	primary heart tissue	1151:1170	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	0	44	link	cell-derived	90:101	arg1	cardiomyocytes					103:116	pluripotent stem cell-derived cardiomyocytes	73:116	pluripotent stem cell-derived cardiomyocytes	73:116	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	2	45	theme	heart	491:495	arg1	function					497:504	heart function	491:504	heart function	491:504	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	8	46	theme	hiPSC-CM	2008:2015	arg1	models					2017:2022	hiPSC-CM models	2008:2022	hiPSC-CM models for studies of human development, disease, and drug testing	2008:2082	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	5	47	theme	mannose	1373:1379	arg1	class					1381:1385	the high mannose class	1364:1385	the high mannose class increased in enriched CM	1364:1410	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	0	48	theme	human	48:52	arg1	cardiomyocytes					54:67	primary human cardiomyocytes	40:67	primary human cardiomyocytes	40:67	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	9	49	dep	immature	2275:2282	arg1	proliferative					2285:2297	proliferative	2285:2297	proliferative	2285:2297	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	8	50	dep	use	1982:1984	arg1	the					1978:1980	the	1978:1980	the	1978:1980	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	7	51	theme	primary	1825:1831	arg1	CM					1833:1834	primary CM	1825:1834	primary CM	1825:1834	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	3	52	used	used	686:689	arg2	we					683:684	we	683:684	we	683:684	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	5	53	theme	N-glycan	1225:1232	arg1	structures					1234:1243	N-glycan structures	1225:1243	N-glycan structures	1225:1243	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	3	54	theme	carbon	710:715	arg1	chromatography					724:737	porous graphitized carbon liquid chromatography	691:737	porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS)	691:783	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	8	55	theme	important	1863:1871	arg1	complement					1873:1882	an important complement	1860:1882	an important complement to current genomic, transcriptomic, and proteomic profiling	1860:1942	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	8	55	theme	important	1863:1871	arg1	observations					1843:1854	These observations	1837:1854	These observations	1837:1854	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	2	56	attach	present	626:632	arg1	heart					654:658	the normal human heart	637:658	the normal human heart	637:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	2	56	attach	present	626:632	arg2	glycans					618:624	the glycans	614:624	the glycans present in the normal human heart	614:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	2	57	theme	glycans	618:624	arg1	view					606:609	a comprehensive view	590:609	a comprehensive view of the glycans present in the normal human heart	590:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	4	58	theme	glycome	1066:1072	arg1	libraries					1041:1049	the first reference structure libraries	1011:1049	the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans	1011:1104	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	3	59	theme	porous	691:696	arg1	chromatography					724:737	porous graphitized carbon liquid chromatography	691:737	porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS)	691:783	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	6	60	theme	primary	1436:1442	arg1	CM					1444:1445	primary CM	1436:1445	primary CM	1436:1445	Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughout in vitro differentiation were observed and differences between primary and hiPSC-CM were revealed.
31972267	7	61	theme	structures	1781:1790	arg1	%					1667:1667	>30%	1664:1667	>30% of the N-glycome significantly changed across these time-points of differentiation	1664:1750	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	7	61	theme	structures	1781:1790	arg1	N-glycome					1676:1684	the N-glycome	1672:1684	the N-glycome significantly changed across these time-points of differentiation	1672:1750	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	7	61	theme	structures	1781:1790	arg1	%					1763:1763	only 23%	1756:1763	only 23% of the N-glycan structures	1756:1790	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	7	61	theme	structures	1781:1790	arg1	structures					1781:1790	the N-glycan structures	1768:1790	the N-glycan structures	1768:1790	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	9	62	theme	regenerative	2136:2147	arg1	efforts					2158:2164	future regenerative medicine efforts	2129:2164	future regenerative medicine efforts	2129:2164	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	8	63	theme	genomic	1895:1901	arg1	profiling					1934:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	6	64	theme	glycan	1531:1536	arg1	profile					1538:1544	the glycan profile	1527:1544	the glycan profile throughout in vitro differentiation	1527:1580	Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughout in vitro differentiation were observed and differences between primary and hiPSC-CM were revealed.
31972267	8	65	theme	disease	2058:2064	arg1	studies					2028:2034	studies	2028:2034	studies of human development, disease, and drug testing	2028:2082	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	2	66	theme	normal	641:646	arg1	heart					654:658	the normal human heart	637:658	the normal human heart	637:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	8	67	theme	transcriptomic	1904:1917	arg1	profiling					1934:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	5	68	theme	enriched	1400:1407	arg1	CM					1409:1410	enriched CM	1400:1410	enriched CM	1400:1410	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	0	69	theme	stage-specific	147:160	arg1	phenotypes					169:178	cell-type and culture stage-specific glycan phenotypes	125:178	cell-type and culture stage-specific glycan phenotypes	125:178	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	6	70	theme	dynamic	1508:1514	arg1	changes					1516:1522	dynamic changes	1508:1522	dynamic changes in the glycan profile throughout in vitro differentiation	1508:1580	Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughout in vitro differentiation were observed and differences between primary and hiPSC-CM were revealed.
31972267	6	71	theme	differentiation	1491:1505	arg1	20-100 days					1476:1486	20-100 days	1476:1486	20-100 days of differentiation	1476:1505	Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughout in vitro differentiation were observed and differences between primary and hiPSC-CM were revealed.
31972267	3	72	theme	glycan	797:802	arg1	libraries					814:822	glycan structure libraries	797:822	glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM)	797:981	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	2	73	theme	comprehensive	592:604	arg1	view					606:609	a comprehensive view	590:609	a comprehensive view of the glycans present in the normal human heart	590:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	2	74	from	heart	654:658	arg1	present					626:632	present	626:632	present	626:632	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	5	75	theme	sample	1266:1271	arg1	type					1273:1276	each sample type	1261:1276	each sample type	1261:1276	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	1	76	from	function	265:272	arg1	health					277:282	health	277:282	health	277:282	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	1	76	from	function	265:272	arg1	disease					288:294	disease	288:294	disease	288:294	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	3	77	theme	primary	828:834	arg1	homogenate					855:864	primary human heart tissue homogenate	828:864	primary human heart tissue homogenate	828:864	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	0	78	theme	pluripotent	73:83	arg1	cardiomyocytes					103:116	pluripotent stem cell-derived cardiomyocytes	73:116	pluripotent stem cell-derived cardiomyocytes	73:116	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	9	79	theme	immature	2275:2282	arg1	hiPSC-CM					2299:2306	immature, proliferative hiPSC-CM	2275:2306	immature, proliferative hiPSC-CM	2275:2306	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	0	80	theme	cell-derived	90:101	arg1	cardiomyocytes					103:116	pluripotent stem cell-derived cardiomyocytes	73:116	pluripotent stem cell-derived cardiomyocytes	73:116	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	5	81	theme	CM	1134:1135	arg1	N-glycome					1121:1129	the N-glycome	1117:1129	the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate	1117:1205	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	1	82	theme	surface	186:192	arg1	glycoproteins					194:206	Cell surface glycoproteins	181:206	Cell surface glycoproteins	181:206	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	3	83	theme	human	901:905	arg1	tissue					913:918	human heart tissue	901:918	human heart tissue	901:918	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	5	84	theme	structures	1308:1317	arg1	signal					1295:1300	the relative signal	1282:1300	the relative signal of 21 structures	1282:1317	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	3	85	theme	heart	842:846	arg1	homogenate					855:864	primary human heart tissue homogenate	828:864	primary human heart tissue homogenate	828:864	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	8	86	theme	models	2017:2022	arg1	use					1982:1984	use	1982:1984	use	1982:1984	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	8	86	theme	models	2017:2022	arg1	interpretation					1990:2003	interpretation	1990:2003	interpretation	1990:2003	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	1	87	theme	signaling	396:404	arg1	[1					406:407	signaling [1]	396:408	signaling [1]	396:408	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	1	88	theme	cardiac	243:249	arg1	structure					251:259	cardiac structure	243:259	cardiac structure	243:259	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	8	89	theme	drug	2071:2074	arg1	testing					2076:2082	drug testing	2071:2082	drug testing	2071:2082	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	0	90	theme	glycan	10:15	arg1	libraries					27:35	Reference glycan structure libraries	0:35	Reference glycan structure libraries of primary human cardiomyocytes	0:67	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	4	91	contain	containing	1074:1083	arg2	O-glycans					1096:1104	O-glycans	1096:1104	O-glycans	1096:1104	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	4	91	contain	containing	1074:1083	arg2	265 N-					1085:1090	265 N-	1085:1090	265 N-	1085:1090	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	4	91	contain	containing	1074:1083	arg1	glycome					1066:1072	the cardiac glycome	1054:1072	the cardiac glycome containing 265 N- and O-glycans	1054:1104	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	7	92	theme	N-glycome	1676:1684	arg1	%					1667:1667	>30%	1664:1667	>30% of the N-glycome significantly changed across these time-points of differentiation	1664:1750	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	7	92	theme	N-glycome	1676:1684	arg1	N-glycome					1676:1684	the N-glycome	1672:1684	the N-glycome significantly changed across these time-points of differentiation	1672:1750	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	7	92	theme	N-glycome	1676:1684	arg1	%					1763:1763	only 23%	1756:1763	only 23% of the N-glycan structures	1756:1790	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	7	92	theme	N-glycome	1676:1684	arg1	structures					1781:1790	the N-glycan structures	1768:1790	the N-glycan structures	1768:1790	Namely, >30% of the N-glycome significantly changed across these time-points of differentiation and only 23% of the N-glycan structures were shared between hiPSC-CM and primary CM.
31972267	2	93	theme	key	473:475	arg1	structures					458:467	glycan structures	451:467	glycan structures	451:467	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	2	93	theme	key	473:475	arg1	modulators					477:486	key modulators	473:486	key modulators of heart function	473:504	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	5	94	theme	relative	1286:1293	arg1	signal					1295:1300	the relative signal	1282:1300	the relative signal of 21 structures	1282:1317	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	9	95	theme	adult	2312:2316	arg1	CM					2326:2327	adult primary CM	2312:2327	adult primary CM	2312:2327	Finally, these data are expected to support future regenerative medicine efforts by informing targets for evaluating the immunogenic potential of hiPSC-CM and harnessing differences between immature, proliferative hiPSC-CM and adult primary CM.
31972267	8	96	theme	human	2039:2043	arg1	development					2045:2055	human development	2039:2055	human development	2039:2055	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	6	97	from	changes	1516:1522	arg1	profile					1538:1544	the glycan profile	1527:1544	the glycan profile throughout in vitro differentiation	1527:1580	Moreover, by comparing primary CM to hiPSC-CM collected during 20-100 days of differentiation, dynamic changes in the glycan profile throughout in vitro differentiation were observed and differences between primary and hiPSC-CM were revealed.
31972267	3	98	theme	stem	951:954	arg1	cell					956:959	human induced pluripotent stem cell	925:959	human induced pluripotent stem cell derived CM (hiPSC-CM)	925:981	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	4	99	theme	structure	1031:1039	arg1	libraries					1041:1049	the first reference structure libraries	1011:1049	the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans	1011:1104	Altogether, we established the first reference structure libraries of the cardiac glycome containing 265 N- and O-glycans.
31972267	2	100	from	present	626:632	arg1	heart					654:658	the normal human heart	637:658	the normal human heart	637:658	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	0	101	theme	primary	40:46	arg1	cardiomyocytes					54:67	primary human cardiomyocytes	40:67	primary human cardiomyocytes	40:67	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	5	102	theme	tissue	1189:1194	arg1	homogenate					1196:1205	heart tissue homogenate	1183:1205	heart tissue homogenate	1183:1205	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	3	103	theme	induced	931:937	arg1	cell					956:959	human induced pluripotent stem cell	925:959	human induced pluripotent stem cell derived CM (hiPSC-CM)	925:981	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	2	104	theme	function	497:504	arg1	structures					458:467	glycan structures	451:467	glycan structures	451:467	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	2	104	theme	function	497:504	arg1	modulators					477:486	key modulators	473:486	key modulators of heart function	473:504	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	5	105	theme	high	1368:1371	arg1	class					1381:1385	the high mannose class	1364:1385	the high mannose class increased in enriched CM	1364:1410	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	2	106	theme	mounting	428:435	arg1	evidence					437:444	mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers	428:562	mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers	428:562	However, despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart.
31972267	0	107	theme	cardiomyocytes	54:67	arg1	libraries					27:35	Reference glycan structure libraries	0:35	Reference glycan structure libraries of primary human cardiomyocytes	0:67	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	0	107	theme	cardiomyocytes	54:67	arg1	cardiomyocytes					103:116	pluripotent stem cell-derived cardiomyocytes	73:116	pluripotent stem cell-derived cardiomyocytes	73:116	Reference glycan structure libraries of primary human cardiomyocytes and pluripotent stem cell-derived cardiomyocytes reveal cell-type and culture stage-specific glycan phenotypes.
31972267	5	108	theme	heart	1159:1163	arg1	tissue					1165:1170	primary heart tissue	1151:1170	primary heart tissue	1151:1170	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
31972267	8	109	theme	proteomic	1924:1932	arg1	profiling					1934:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	current genomic, transcriptomic, and proteomic profiling	1887:1942	These observations are an important complement to current genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing.
31972267	1	110	theme	proper	358:363	arg1	folding					373:379	proper protein folding	358:379	proper protein folding	358:379	Cell surface glycoproteins play critical roles in maintaining cardiac structure and function in health and disease and the glycan-moiety attached to the protein is critical for proper protein folding, stability and signaling [1].
31972267	3	111	theme	current	668:674	arg1	study					676:680	the current study	664:680	the current study	664:680	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	3	112	theme	graphitized	698:708	arg1	chromatography					724:737	porous graphitized carbon liquid chromatography	691:737	porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS)	691:783	In the current study, we used porous graphitized carbon liquid chromatography interfaced with mass spectrometry (PGC-LC-MS) to generate glycan structure libraries for primary human heart tissue homogenate, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM).
31972267	5	113	theme	structures	1234:1243	arg1	pool					1217:1220	the same pool	1208:1220	the same pool of N-glycan structures	1208:1243	Comparing the N-glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, the same pool of N-glycan structures was detected in each sample type but the relative signal of 21 structures significantly differed between samples, with the high mannose class increased in enriched CM.
33263330	7	0	theme	structural	1424:1433	arg1	studies					1435:1441	structural studies	1424:1441	structural studies	1424:1441	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	4	1	theme	proteins	694:701	arg1	crystals					677:684	diffraction-quality crystals	657:684	diffraction-quality crystals of such proteins and their complexes	657:721	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	2	2	theme	binding	411:417	arg1	kinetics					419:426	the binding kinetics	407:426	the binding kinetics underlying protein interactions	407:458	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	0	3	attach	derived	38:44	arg1	line					79:82	the GlycoDelete HEK293 cell line	51:82	the GlycoDelete HEK293 cell line	51:82	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	0	3	attach	derived	38:44	arg2	proteins					29:36	Homogeneously N-glycosylated proteins	0:36	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line	0:82	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	4	4	theme	glycosylation	771:783	arg1	patterns					785:792	glycosylation patterns	771:792	glycosylation patterns	771:792	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	2	5	theme	key	315:317	arg1	modification					336:347	a key post-translation modification	313:347	a key post-translation modification that critically affects protein folding and stability	313:401	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	7	6	dep	extent	1264:1269	arg1	the					1260:1262	the	1260:1262	the	1260:1262	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	7	7	theme	ensuing	1239:1245	arg1	reduction					1247:1255	The ensuing reduction	1235:1255	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches	1235:1383	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	2	8	theme	protein	373:379	arg1	folding					381:387	protein folding	373:387	protein folding	373:387	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	5	9	theme	glycan	991:996	arg1	stumps					998:1003	short glycan stumps	985:1003	short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid	985:1061	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	5	9	theme	glycan	991:996	arg1	N-glycans					972:980	N-glycans	972:980	N-glycans	972:980	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	6	10	theme	syndrome	1096:1103	arg1	molecule					1119:1126	human Down syndrome cell-adhesion molecule	1085:1126	human Down syndrome cell-adhesion molecule	1085:1126	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	8	11	from	glycan	1630:1635	arg1	crystals					1660:1667	diffraction-quality crystals	1640:1667	diffraction-quality crystals	1640:1667	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	6	12	theme	human	1085:1089	arg1	syndrome					1096:1103	human Down syndrome	1085:1103	human Down syndrome cell-adhesion molecule	1085:1126	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	4	13	theme	type	763:766	arg1	modification					738:749	modification	738:749	modification of both the type of glycosylation patterns and their extent	738:809	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	9	14	theme	GlycoDelete	1694:1704	arg1	option					1748:1753	a valuable go-to option	1731:1753	a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy	1731:1898	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	9	14	theme	GlycoDelete	1694:1704	arg1	line					1711:1714	the GlycoDelete cell line	1690:1714	the GlycoDelete cell line	1690:1714	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	8	15	theme	third	1484:1488	arg1	implementation					1501:1514	a third successful implementation	1482:1514	a third successful implementation of the GlycoDelete technology focusing on murine IL-12B	1482:1570	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	1	16	theme	glycoproteins	151:163	arg1	studies					140:146	Structural studies	129:146	Structural studies of glycoproteins and their complexes	129:183	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	9	17	theme	glycoproteins	1789:1801	arg1	production					1763:1772	the production	1759:1772	the production of homogeneous glycoproteins and their complexes	1759:1821	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	5	18	from	glycoproteins	866:878	arg1	line					931:934	the GlycoDelete human embryonic kidney 293 cell line	883:934	the GlycoDelete human embryonic kidney 293 cell line	883:934	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	1	19	from	roles	222:226	arg1	physiology					238:247	normal physiology	231:247	normal physiology	231:247	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	1	19	from	roles	222:226	arg1	disease					253:259	disease	253:259	disease	253:259	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	4	20	theme	extent	804:809	arg1	modification					738:749	modification	738:749	modification of both the type of glycosylation patterns and their extent	738:809	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	0	21	theme	cell	74:77	arg1	line					79:82	the GlycoDelete HEK293 cell line	51:82	the GlycoDelete HEK293 cell line	51:82	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	2	22	theme	N-linked	289:296	arg1	glycosylation					298:310	N-linked glycosylation	289:310	N-linked glycosylation	289:310	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	8	23	theme	technology	1535:1544	arg1	implementation					1501:1514	a third successful implementation	1482:1514	a third successful implementation of the GlycoDelete technology focusing on murine IL-12B	1482:1570	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	5	24	theme	GlycoDelete	887:897	arg1	kidney					915:920	GlycoDelete human embryonic kidney 293	887:924	the GlycoDelete human embryonic kidney 293 cell line	883:934	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	9	25	theme	go-to	1742:1746	arg1	option					1748:1753	a valuable go-to option	1731:1753	a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy	1731:1898	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	9	25	theme	go-to	1742:1746	arg1	line					1711:1714	the GlycoDelete cell line	1690:1714	the GlycoDelete cell line	1690:1714	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	6	26	theme	colony-stimulating	1132:1149	arg1	receptor					1160:1167	colony-stimulating factor 1 receptor	1132:1167	colony-stimulating factor 1 receptor	1132:1167	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	6	27	theme	molecule	1119:1126	arg1	fragments					1072:1080	Protein fragments	1064:1080	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor	1064:1167	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	7	28	theme	glycoengineering	1357:1372	arg1	approaches					1374:1383	alternative glycoengineering approaches	1345:1383	alternative glycoengineering approaches	1345:1383	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	9	29	theme	homogeneous	1777:1787	arg1	glycoproteins					1789:1801	homogeneous glycoproteins	1777:1801	homogeneous glycoproteins	1777:1801	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	6	30	theme	GlycoDelete	1192:1202	arg1	line					1209:1212	the GlycoDelete cell line	1188:1212	the GlycoDelete cell line	1188:1212	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	3	31	theme	homogeneous	528:538	arg1	preparations					548:559	yielding homogeneous protein preparations	519:559	yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods	519:629	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	5	32	theme	embryonic	905:913	arg1	kidney					915:920	GlycoDelete human embryonic kidney 293	887:924	the GlycoDelete human embryonic kidney 293 cell line	883:934	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	0	33	gly	N-glycosylated	14:27	arg1	proteins					29:36	Homogeneously N-glycosylated proteins	0:36	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line	0:82	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	3	34	theme	N-linked	470:477	arg1	glycosylation					479:491	N-linked glycosylation	470:491	N-linked glycosylation	470:491	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	3	34	theme	N-linked	470:477	arg1	impediment					505:514	an impediment	502:514	an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods	502:629	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	0	35	theme	GlycoDelete	55:65	arg1	line					79:82	the GlycoDelete HEK293 cell line	51:82	the GlycoDelete HEK293 cell line	51:82	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	9	36	theme	structural	1827:1836	arg1	studies					1838:1844	structural studies	1827:1844	structural studies by X-ray crystallography and cryo-electron microscopy	1827:1898	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	9	37	gly	glycoproteins	1789:1801	arg1	glycoproteins					1789:1801	homogeneous glycoproteins	1777:1801	homogeneous glycoproteins	1777:1801	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	9	38	theme	complexes	1813:1821	arg1	production					1763:1772	the production	1759:1772	the production of homogeneous glycoproteins and their complexes	1759:1821	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	3	39	theme	structure	565:573	arg1	determination					575:587	structure determination	565:587	structure determination by X-ray crystallography or other methods	565:629	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	4	40	theme	complexes	713:721	arg1	crystals					677:684	diffraction-quality crystals	657:684	diffraction-quality crystals of such proteins and their complexes	657:721	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	3	41	theme	protein	540:546	arg1	preparations					548:559	yielding homogeneous protein preparations	519:559	yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods	519:629	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	8	42	theme	diffraction-quality	1640:1658	arg1	crystals					1660:1667	diffraction-quality crystals	1640:1667	diffraction-quality crystals	1640:1667	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	3	43	theme	other	617:621	arg1	methods					623:629	other methods	617:629	other methods	617:629	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	0	44	theme	HEK293	67:72	arg1	line					79:82	the GlycoDelete HEK293 cell line	51:82	the GlycoDelete HEK293 cell line	51:82	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	7	45	theme	X-ray	1446:1450	arg1	crystallography					1452:1466	X-ray crystallography	1446:1466	X-ray crystallography	1446:1466	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	9	46	theme	cryo-electron	1875:1887	arg1	microscopy					1889:1898	cryo-electron microscopy	1875:1898	cryo-electron microscopy	1875:1898	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	4	47	theme	such	689:692	arg1	proteins					694:701	such proteins	689:701	such proteins	689:701	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	9	48	theme	valuable	1733:1740	arg1	option					1748:1753	a valuable go-to option	1731:1753	a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy	1731:1898	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	9	48	theme	valuable	1733:1740	arg1	line					1711:1714	the GlycoDelete cell line	1690:1714	the GlycoDelete cell line	1690:1714	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	2	49	theme	post-translation	319:334	arg1	modification					336:347	a key post-translation modification	313:347	a key post-translation modification that critically affects protein folding and stability	313:401	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	7	50	theme	N-glycosylation	1289:1303	arg1	extent					1264:1269	extent	1264:1269	extent	1264:1269	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	7	50	theme	N-glycosylation	1289:1303	arg1	complexity					1275:1284	complexity	1275:1284	complexity	1275:1284	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	7	51	theme	productive	1399:1408	arg1	deployment					1410:1419	their productive deployment	1393:1419	their productive deployment	1393:1419	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	5	52	theme	short	985:989	arg1	stumps					998:1003	short glycan stumps	985:1003	short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid	985:1061	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	5	52	theme	short	985:989	arg1	N-glycans					972:980	N-glycans	972:980	N-glycans	972:980	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	6	53	theme	cell-adhesion	1105:1117	arg1	molecule					1119:1126	human Down syndrome cell-adhesion molecule	1085:1126	human Down syndrome cell-adhesion molecule	1085:1126	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	4	54	theme	patterns	785:792	arg1	type					763:766	the type	759:766	the type of glycosylation patterns	759:792	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	4	54	theme	patterns	785:792	arg1	extent					804:809	their extent	798:809	their extent	798:809	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	1	55	gly	glycoproteins	151:163	arg1	glycoproteins					151:163	glycoproteins	151:163	glycoproteins	151:163	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	1	56	theme	normal	231:236	arg1	physiology					238:247	normal physiology	231:247	normal physiology	231:247	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	6	57	theme	Down	1091:1094	arg1	syndrome					1096:1103	human Down syndrome	1085:1103	human Down syndrome cell-adhesion molecule	1085:1126	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	2	58	gly	glycoproteins	267:279	arg1	glycoproteins					267:279	Most glycoproteins	262:279	Most glycoproteins	262:279	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	3	59	link	N-linked	470:477	arg1	glycosylation					479:491	N-linked glycosylation	470:491	N-linked glycosylation	470:491	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	3	59	link	N-linked	470:477	arg1	impediment					505:514	an impediment	502:514	an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods	502:629	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	2	60	theme	Most	262:265	arg1	glycoproteins					267:279	Most glycoproteins	262:279	Most glycoproteins	262:279	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	9	61	theme	cell	1706:1709	arg1	option					1748:1753	a valuable go-to option	1731:1753	a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy	1731:1898	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	9	61	theme	cell	1706:1709	arg1	line					1711:1714	the GlycoDelete cell line	1690:1714	the GlycoDelete cell line	1690:1714	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	6	62	theme	Protein	1064:1070	arg1	fragments					1072:1080	Protein fragments	1064:1080	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor	1064:1167	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	5	63	theme	sialic	1051:1056	arg1	acid					1058:1061	sialic acid	1051:1061	sialic acid	1051:1061	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	8	64	theme	successful	1490:1499	arg1	implementation					1501:1514	a third successful implementation	1482:1514	a third successful implementation of the GlycoDelete technology focusing on murine IL-12B	1482:1570	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	1	65	theme	complexes	175:183	arg1	studies					140:146	Structural studies	129:146	Structural studies of glycoproteins and their complexes	129:183	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	6	66	theme	receptor	1160:1167	arg1	fragments					1072:1080	Protein fragments	1064:1080	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor	1064:1167	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	0	67	theme	diffraction-quality	91:109	arg1	crystallogenesis					111:126	diffraction-quality crystallogenesis	91:126	diffraction-quality crystallogenesis	91:126	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	1	68	theme	critical	193:200	arg1	insights					202:209	critical insights	193:209	critical insights into their roles in normal physiology and disease	193:259	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	6	69	theme	factor	1151:1156	arg1	receptor					1160:1167	colony-stimulating factor 1 receptor	1132:1167	colony-stimulating factor 1 receptor	1132:1167	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	8	70	theme	GlycoDelete	1523:1533	arg1	technology					1535:1544	the GlycoDelete technology	1519:1544	the GlycoDelete technology focusing on murine IL-12B	1519:1570	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	2	71	link	N-linked	289:296	arg1	glycosylation					298:310	N-linked glycosylation	289:310	N-linked glycosylation	289:310	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	5	72	gly	glycoproteins	866:878	arg1	glycoproteins					866:878	target glycoproteins	859:878	target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid	859:1061	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	7	73	theme	alternative	1345:1355	arg1	approaches					1374:1383	alternative glycoengineering approaches	1345:1383	alternative glycoengineering approaches	1345:1383	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	8	74	theme	murine	1558:1563	arg1	IL-12B					1565:1570	murine IL-12B	1558:1570	murine IL-12B	1558:1570	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	3	75	theme	yielding	519:526	arg1	preparations					548:559	yielding homogeneous protein preparations	519:559	yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods	519:629	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	0	76	theme	N-glycosylated	14:27	arg1	proteins					29:36	Homogeneously N-glycosylated proteins	0:36	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line	0:82	Homogeneously N-glycosylated proteins derived from the GlycoDelete HEK293 cell line enable diffraction-quality crystallogenesis.
33263330	4	77	theme	diffraction-quality	657:675	arg1	crystals					677:684	diffraction-quality crystals	657:684	diffraction-quality crystals of such proteins and their complexes	657:721	In particular, obtaining diffraction-quality crystals of such proteins and their complexes often requires modification of both the type of glycosylation patterns and their extent.
33263330	7	78	theme	protein	1313:1319	arg1	molecules					1321:1329	both protein molecules	1308:1329	both protein molecules compared with alternative glycoengineering approaches	1308:1383	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	1	79	theme	Structural	129:138	arg1	studies					140:146	Structural studies	129:146	Structural studies of glycoproteins and their complexes	129:183	Structural studies of glycoproteins and their complexes provide critical insights into their roles in normal physiology and disease.
33263330	6	80	theme	cell	1204:1207	arg1	line					1209:1212	the GlycoDelete cell line	1188:1212	the GlycoDelete cell line	1188:1212	Protein fragments of human Down syndrome cell-adhesion molecule and colony-stimulating factor 1 receptor were obtained from the GlycoDelete cell line for crystallization.
33263330	7	81	from	reduction	1247:1255	arg1	extent					1264:1269	extent	1264:1269	extent	1264:1269	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	7	81	from	reduction	1247:1255	arg1	molecules					1321:1329	both protein molecules	1308:1329	both protein molecules compared with alternative glycoengineering approaches	1308:1383	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	7	81	from	reduction	1247:1255	arg1	complexity					1275:1284	complexity	1275:1284	complexity	1275:1284	The ensuing reduction in the extent and complexity of N-glycosylation in both protein molecules compared with alternative glycoengineering approaches enabled their productive deployment in structural studies by X-ray crystallography.
33263330	2	82	theme	protein	439:445	arg1	interactions					447:458	protein interactions	439:458	protein interactions	439:458	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	5	83	theme	human	899:903	arg1	kidney					915:920	GlycoDelete human embryonic kidney 293	887:924	the GlycoDelete human embryonic kidney 293 cell line	883:934	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	5	84	theme	target	859:864	arg1	glycoproteins					866:878	target glycoproteins	859:878	target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid	859:1061	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	5	85	theme	kidney	915:920	arg1	line					931:934	the GlycoDelete human embryonic kidney 293 cell line	883:934	the GlycoDelete human embryonic kidney 293 cell line	883:934	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	3	86	theme	X-ray	592:596	arg1	crystallography					598:612	X-ray crystallography	592:612	X-ray crystallography	592:612	However, N-linked glycosylation is often an impediment to yielding homogeneous protein preparations for structure determination by X-ray crystallography or other methods.
33263330	8	87	theme	immature	1621:1628	arg1	glycan					1630:1635	an immature glycan	1618:1635	an immature glycan in diffraction-quality crystals	1618:1667	Furthermore, a third successful implementation of the GlycoDelete technology focusing on murine IL-12B is shown to lead to N-glycosylation featuring an immature glycan in diffraction-quality crystals.
33263330	9	88	theme	X-ray	1849:1853	arg1	crystallography					1855:1869	X-ray crystallography	1849:1869	X-ray crystallography	1849:1869	It is proposed that the GlycoDelete cell line could serve as a valuable go-to option for the production of homogeneous glycoproteins and their complexes for structural studies by X-ray crystallography and cryo-electron microscopy.
33263330	5	89	theme	cell	926:929	arg1	line					931:934	the GlycoDelete human embryonic kidney 293 cell line	883:934	the GlycoDelete human embryonic kidney 293 cell line	883:934	Here, we demonstrate the benefits of producing target glycoproteins in the GlycoDelete human embryonic kidney 293 cell line that has been engineered to produce N-glycans as short glycan stumps comprising N-acetylglucosamine, galactose and sialic acid.
33263330	2	90	contain	contain	281:287	arg1	glycoproteins					267:279	Most glycoproteins	262:279	Most glycoproteins	262:279	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	2	90	contain	contain	281:287	arg2	glycosylation					298:310	N-linked glycosylation	289:310	N-linked glycosylation	289:310	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	2	90	contain	contain	281:287	arg2	kinetics					419:426	the binding kinetics	407:426	the binding kinetics underlying protein interactions	407:458	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
33263330	2	90	contain	contain	281:287	arg2	modification					336:347	a key post-translation modification	313:347	a key post-translation modification that critically affects protein folding and stability	313:401	Most glycoproteins contain N-linked glycosylation, a key post-translation modification that critically affects protein folding and stability and the binding kinetics underlying protein interactions.
34551980	4	0	theme	available	958:966	arg1	assays					984:989	available high-throughput assays	958:989	available high-throughput assays	958:989	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	3	1	theme	protein	734:740	arg1	variants					714:721	all possible glycosylation site variants	682:721	all possible glycosylation site variants of a given protein	682:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	2	2	theme	glycosylation	319:331	arg1	use					312:314	the routine use	300:314	the routine use of glycosylation as a strategy for engineering proteins with advantageous properties	300:399	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	7	3	theme	protein-protein	1765:1779	arg1	interface					1781:1789	a protein-protein interface	1763:1789	a protein-protein interface	1763:1789	Structural models suggested that affinity was improved by creating novel interfacial contacts with a glycan at the periphery of a protein-protein interface.
34551980	3	4	theme	combinatorial	586:598	arg1	strategy					600:607	a combinatorial strategy	584:607	a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria	584:819	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	6	5	theme	modification	1621:1632	arg1	location					1605:1612	the precise location	1593:1612	the precise location of the modification	1593:1632	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	5	6	theme	acceptor	1199:1206	arg1	A					1288:1288	bovine pancreatic ribonuclease A	1257:1288	bovine pancreatic ribonuclease A	1257:1288	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	6	theme	acceptor	1199:1206	arg1	Im7					1252:1254	bacterial immunity protein Im7	1225:1254	bacterial immunity protein Im7	1225:1254	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	6	theme	acceptor	1199:1206	arg1	antibody					1327:1334	human anti-HER2 single-chain Fv antibody	1295:1334	human anti-HER2 single-chain Fv antibody	1295:1334	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	6	theme	acceptor	1199:1206	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	8	7	theme	glycoprotein	1901:1912	arg1	space					1925:1929	glycoprotein structural space	1901:1929	glycoprotein structural space	1901:1929	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	3	8	theme	rapid	839:843	arg1	determination					845:857	rapid determination	839:857	rapid determination of glycosylatable sites in the protein	839:896	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	5	9	theme	approach	1152:1159	arg1	utility					1136:1142	The utility	1132:1142	The utility of this approach	1132:1159	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	3	10	theme	scanning	624:631	arg1	glycomutagenesis					633:648	shotgun scanning glycomutagenesis	616:648	shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria	616:819	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	8	11	theme	space	1925:1929	arg1	regions					1890:1896	unexplored regions	1879:1896	unexplored regions of glycoprotein structural space	1879:1929	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	1	12	theme	common	126:131	arg1	modification					141:152	a common protein modification	124:152	a common protein modification	124:152	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	1	12	theme	common	126:131	arg1	capacity					206:213	the capacity to greatly influence the biological and biophysical properties of proteins	202:288	the capacity to greatly influence the biological and biophysical properties of proteins	202:288	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	2	13	theme	glycan	524:529	arg1	installation					531:542	glycan installation	524:542	glycan installation	524:542	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	4	14	theme	glycan	1087:1092	arg1	conjugation					1094:1104	glycan conjugation	1087:1104	glycan conjugation	1087:1104	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	3	15	theme	sites	877:881	arg1	determination					845:857	rapid determination	839:857	rapid determination of glycosylatable sites in the protein	839:896	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	6	16	theme	glycovariants	1496:1508	arg1	activity					1479:1486	activity	1479:1486	activity	1479:1486	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	6	16	theme	glycovariants	1496:1508	arg1	stability					1465:1473	stability	1465:1473	stability	1465:1473	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	5	17	theme	protein	1244:1250	arg1	Im7					1252:1254	bacterial immunity protein Im7	1225:1254	bacterial immunity protein Im7	1225:1254	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	17	theme	protein	1244:1250	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	3	18	theme	DNA	659:661	arg1	libraries					663:671	DNA libraries	659:671	DNA libraries encoding all possible glycosylation site variants of a given protein	659:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	1	19	theme	asparagine-linked	155:171	arg1	glycosylation					184:196	asparagine-linked (N-linked) glycosylation	155:196	asparagine-linked (N-linked) glycosylation	155:196	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	7	20	theme	interfacial	1708:1718	arg1	contacts					1720:1727	novel interfacial contacts	1702:1727	novel interfacial contacts	1702:1727	Structural models suggested that affinity was improved by creating novel interfacial contacts with a glycan at the periphery of a protein-protein interface.
34551980	8	21	theme	desirable	1972:1980	arg1	properties					1982:1991	desirable properties	1972:1991	desirable properties	1972:1991	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	1	22	theme	N-linked	174:181	arg1	glycosylation					184:196	asparagine-linked (N-linked) glycosylation	155:196	asparagine-linked (N-linked) glycosylation	155:196	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	5	23	theme	high	1444:1447	arg1	efficiency					1449:1458	relatively high efficiency	1433:1458	relatively high efficiency	1433:1458	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	24	theme	bacterial	1225:1233	arg1	Im7					1252:1254	bacterial immunity protein Im7	1225:1254	bacterial immunity protein Im7	1225:1254	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	24	theme	bacterial	1225:1233	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	0	25	theme	simple	37:42	arg1	strategy					58:65	A simple and efficient strategy	35:65	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.	0:119	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.
34551980	2	26	theme	installation	531:542	arg1	consequences					508:519	the consequences	504:519	the consequences of glycan installation	504:542	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	0	27	theme	Shotgun	0:6	arg1	glycomutagenesis					17:32	Shotgun scanning glycomutagenesis	0:32	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.	0:119	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.
34551980	0	28	gly	neoglycoproteins	103:118	arg1	neoglycoproteins					103:118	neoglycoproteins	103:118	neoglycoproteins	103:118	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.
34551980	1	29	contain	has	198:200	arg2	modification					141:152	a common protein modification	124:152	a common protein modification	124:152	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	1	29	contain	has	198:200	arg1	glycosylation					184:196	asparagine-linked (N-linked) glycosylation	155:196	asparagine-linked (N-linked) glycosylation	155:196	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	1	29	contain	has	198:200	arg2	capacity					206:213	the capacity to greatly influence the biological and biophysical properties of proteins	202:288	the capacity to greatly influence the biological and biophysical properties of proteins	202:288	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	2	30	theme	large	453:457	arg1	collections					459:469	large collections	453:469	large collections of glycoproteins	453:486	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	5	31	theme	positions	1414:1422	arg1	number					1404:1409	a large number	1396:1409	a large number of positions	1396:1422	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	4	32	gly	neoglycoproteins	913:928	arg1	neoglycoproteins					913:928	The resulting neoglycoproteins	899:928	The resulting neoglycoproteins	899:928	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	5	33	theme	anti-HER2	1301:1309	arg1	antibody					1327:1334	human anti-HER2 single-chain Fv antibody	1295:1334	human anti-HER2 single-chain Fv antibody	1295:1334	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	33	theme	anti-HER2	1301:1309	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	7	34	theme	interface	1781:1789	arg1	periphery					1750:1758	the periphery	1746:1758	the periphery of a protein-protein interface	1746:1789	Structural models suggested that affinity was improved by creating novel interfacial contacts with a glycan at the periphery of a protein-protein interface.
34551980	4	35	theme	protein	1114:1120	arg1	backbone					1122:1129	a protein backbone	1112:1129	a protein backbone	1112:1129	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	3	36	theme	site	709:712	arg1	variants					714:721	all possible glycosylation site variants	682:721	all possible glycosylation site variants of a given protein	682:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	5	37	theme	pancreatic	1264:1273	arg1	ribonuclease					1275:1286	bovine pancreatic ribonuclease	1257:1286	bovine pancreatic ribonuclease A	1257:1288	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	3	38	from	sites	877:881	arg1	protein					890:896	the protein	886:896	the protein	886:896	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	3	39	theme	possible	686:693	arg1	variants					714:721	all possible glycosylation site variants	682:721	all possible glycosylation site variants of a given protein	682:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	2	40	theme	engineering	351:361	arg1	proteins					363:370	engineering proteins	351:370	engineering proteins with advantageous properties	351:399	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	3	41	theme	given	728:732	arg1	protein					734:740	a given protein	726:740	a given protein	726:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	0	42	dep	glycomutagenesis	17:32	arg1	strategy					58:65	A simple and efficient strategy	35:65	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.	0:119	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.
34551980	5	43	dep	proteins	1208:1215	arg1	A					1288:1288	bovine pancreatic ribonuclease A	1257:1288	bovine pancreatic ribonuclease A	1257:1288	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	43	dep	proteins	1208:1215	arg1	Im7					1252:1254	bacterial immunity protein Im7	1225:1254	bacterial immunity protein Im7	1225:1254	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	43	dep	proteins	1208:1215	arg1	antibody					1327:1334	human anti-HER2 single-chain Fv antibody	1295:1334	human anti-HER2 single-chain Fv antibody	1295:1334	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	43	dep	proteins	1208:1215	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	44	theme	Fv	1324:1325	arg1	antibody					1327:1334	human anti-HER2 single-chain Fv antibody	1295:1334	human anti-HER2 single-chain Fv antibody	1295:1334	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	44	theme	Fv	1324:1325	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	3	45	gly	glycosylation	695:707	arg2	site					709:712	all possible glycosylation site variants	682:721	all possible glycosylation site variants of a given protein	682:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	3	45	gly	glycosylation	695:707	arg2	variants					714:721	all possible glycosylation site variants	682:721	all possible glycosylation site variants of a given protein	682:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	2	46	theme	routine	304:310	arg1	use					312:314	the routine use	300:314	the routine use of glycosylation as a strategy for engineering proteins with advantageous properties	300:399	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	1	47	theme	proteins	281:288	arg1	properties					267:276	the biological and biophysical properties	236:276	the biological and biophysical properties of proteins	236:288	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	4	48	theme	high-throughput	968:982	arg1	assays					984:989	available high-throughput assays	958:989	available high-throughput assays	958:989	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	3	49	theme	glycosylation-competent	788:810	arg1	bacteria					812:819	glycosylation-competent bacteria	788:819	glycosylation-competent bacteria	788:819	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	8	50	theme	glycomutagenesis	1828:1843	arg1	workflow					1845:1852	our glycomutagenesis workflow	1824:1852	our glycomutagenesis workflow	1824:1852	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	8	51	with	neoglycoproteins	1950:1965	arg1	properties					1982:1991	desirable properties	1972:1991	desirable properties	1972:1991	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	5	52	theme	different	1189:1197	arg1	A					1288:1288	bovine pancreatic ribonuclease A	1257:1288	bovine pancreatic ribonuclease A	1257:1288	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	52	theme	different	1189:1197	arg1	Im7					1252:1254	bacterial immunity protein Im7	1225:1254	bacterial immunity protein Im7	1225:1254	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	52	theme	different	1189:1197	arg1	antibody					1327:1334	human anti-HER2 single-chain Fv antibody	1295:1334	human anti-HER2 single-chain Fv antibody	1295:1334	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	52	theme	different	1189:1197	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	8	53	theme	unexplored	1879:1888	arg1	regions					1890:1896	unexplored regions	1879:1896	unexplored regions of glycoprotein structural space	1879:1929	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	3	54	theme	glycosylatable	862:875	arg1	sites					877:881	glycosylatable sites	862:881	glycosylatable sites in the protein	862:896	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	3	55	theme	shotgun	616:622	arg1	glycomutagenesis					633:648	shotgun scanning glycomutagenesis	616:648	shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria	616:819	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	2	56	with	proteins	363:370	arg1	properties					390:399	advantageous properties	377:399	advantageous properties	377:399	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	8	57	theme	structural	1914:1923	arg1	space					1925:1929	glycoprotein structural space	1901:1929	glycoprotein structural space	1901:1929	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	1	58	theme	protein	133:139	arg1	modification					141:152	a common protein modification	124:152	a common protein modification	124:152	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	1	58	theme	protein	133:139	arg1	capacity					206:213	the capacity to greatly influence the biological and biophysical properties of proteins	202:288	the capacity to greatly influence the biological and biophysical properties of proteins	202:288	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	5	59	theme	large	1398:1402	arg1	number					1404:1409	a large number	1396:1409	a large number of positions	1396:1422	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	7	60	theme	novel	1702:1706	arg1	contacts					1720:1727	novel interfacial contacts	1702:1727	novel interfacial contacts	1702:1727	Structural models suggested that affinity was improved by creating novel interfacial contacts with a glycan at the periphery of a protein-protein interface.
34551980	8	61	gly	glycoprotein	1901:1912	arg1	glycoprotein					1901:1912	glycoprotein structural space	1901:1929	glycoprotein structural space	1901:1929	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	6	62	link	N-linked	1536:1543	arg1	glycans					1545:1551	N-linked glycans	1536:1551	N-linked glycans	1536:1551	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	6	63	theme	many	1491:1494	arg1	glycovariants					1496:1508	many glycovariants	1491:1508	many glycovariants	1491:1508	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	6	64	dep	stability	1465:1473	arg1	The					1461:1463	The	1461:1463	The	1461:1463	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	8	65	theme	custom-made	1938:1948	arg1	neoglycoproteins					1950:1965	custom-made neoglycoproteins	1938:1965	custom-made neoglycoproteins with desirable properties	1938:1991	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	4	66	theme	conjugation	1094:1104	arg1	consequences					1071:1082	the structural and functional consequences	1041:1082	the structural and functional consequences of glycan conjugation along a protein backbone	1041:1129	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	3	67	from	determination	845:857	arg1	protein					890:896	the protein	886:896	the protein	886:896	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	5	68	theme	N-glycan	1373:1380	arg1	attachment					1382:1391	N-glycan attachment	1373:1391	N-glycan attachment	1373:1391	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	69	theme	bovine	1257:1262	arg1	ribonuclease					1275:1286	bovine pancreatic ribonuclease	1257:1286	bovine pancreatic ribonuclease A	1257:1288	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	4	70	theme	structural	1045:1054	arg1	consequences					1071:1082	the structural and functional consequences	1041:1082	the structural and functional consequences of glycan conjugation along a protein backbone	1041:1129	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	7	71	from	periphery	1750:1758	arg1	glycan					1736:1741	a glycan	1734:1741	a glycan at the periphery of a protein-protein interface	1734:1789	Structural models suggested that affinity was improved by creating novel interfacial contacts with a glycan at the periphery of a protein-protein interface.
34551980	4	72	theme	functional	1060:1069	arg1	consequences					1071:1082	the structural and functional consequences	1041:1082	the structural and functional consequences of glycan conjugation along a protein backbone	1041:1129	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	0	73	theme	scanning	8:15	arg1	glycomutagenesis					17:32	Shotgun scanning glycomutagenesis	0:32	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.	0:119	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.
34551980	5	74	theme	immunity	1235:1242	arg1	Im7					1252:1254	bacterial immunity protein Im7	1225:1254	bacterial immunity protein Im7	1225:1254	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	74	theme	immunity	1235:1242	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	75	theme	human	1295:1299	arg1	antibody					1327:1334	human anti-HER2 single-chain Fv antibody	1295:1334	human anti-HER2 single-chain Fv antibody	1295:1334	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	75	theme	human	1295:1299	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	1	76	link	N-linked	174:181	arg1	glycosylation					184:196	asparagine-linked (N-linked) glycosylation	155:196	asparagine-linked (N-linked) glycosylation	155:196	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	3	77	theme	glycosylation	695:707	arg1	variants					714:721	all possible glycosylation site variants	682:721	all possible glycosylation site variants of a given protein	682:740	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	6	78	theme	N-linked	1536:1543	arg1	glycans					1545:1551	N-linked glycans	1536:1551	N-linked glycans	1536:1551	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	5	79	theme	single-chain	1311:1322	arg1	antibody					1327:1334	human anti-HER2 single-chain Fv antibody	1295:1334	human anti-HER2 single-chain Fv antibody	1295:1334	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	79	theme	single-chain	1311:1322	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	1	80	link	asparagine-linked	155:171	arg1	glycosylation					184:196	asparagine-linked (N-linked) glycosylation	155:196	asparagine-linked (N-linked) glycosylation	155:196	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	8	81	gly	neoglycoproteins	1950:1965	arg1	neoglycoproteins					1950:1965	custom-made neoglycoproteins	1938:1965	custom-made neoglycoproteins with desirable properties	1938:1991	Importantly, we anticipate that our glycomutagenesis workflow should provide access to unexplored regions of glycoprotein structural space and to custom-made neoglycoproteins with desirable properties.
34551980	0	82	theme	efficient	48:56	arg1	strategy					58:65	A simple and efficient strategy	35:65	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.	0:119	Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.
34551980	5	83	theme	ribonuclease	1275:1286	arg1	A					1288:1288	bovine pancreatic ribonuclease A	1257:1288	bovine pancreatic ribonuclease A	1257:1288	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	5	83	theme	ribonuclease	1275:1286	arg1	proteins					1208:1215	three different acceptor proteins	1183:1215	three different acceptor proteins	1183:1215	The utility of this approach was demonstrated with three different acceptor proteins, namely bacterial immunity protein Im7, bovine pancreatic ribonuclease A, and human anti-HER2 single-chain Fv antibody, all of which were found to tolerate N-glycan attachment at a large number of positions and with relatively high efficiency.
34551980	2	84	gly	glycoproteins	474:486	arg1	glycoproteins					474:486	glycoproteins	474:486	glycoproteins	474:486	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	2	85	theme	glycoproteins	474:486	arg1	collections					459:469	large collections	453:469	large collections of glycoproteins	453:486	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	4	86	theme	resulting	903:911	arg1	neoglycoproteins					913:928	The resulting neoglycoproteins	899:928	The resulting neoglycoproteins	899:928	The resulting neoglycoproteins can be readily subjected to available high-throughput assays, making it possible to systematically investigate the structural and functional consequences of glycan conjugation along a protein backbone.
34551980	7	87	theme	Structural	1635:1644	arg1	models					1646:1651	Structural models	1635:1651	Structural models	1635:1651	Structural models suggested that affinity was improved by creating novel interfacial contacts with a glycan at the periphery of a protein-protein interface.
34551980	3	88	from	protein	890:896	arg1	determination					845:857	rapid determination	839:857	rapid determination of glycosylatable sites in the protein	839:896	To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein.
34551980	6	89	theme	precise	1597:1603	arg1	location					1605:1612	the precise location	1593:1612	the precise location of the modification	1593:1632	The stability and activity of many glycovariants was measurably altered by N-linked glycans in a manner that critically depended on the precise location of the modification.
34551980	1	90	theme	biological	240:249	arg1	properties					267:276	the biological and biophysical properties	236:276	the biological and biophysical properties of proteins	236:288	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34551980	2	91	theme	advantageous	377:388	arg1	properties					390:399	advantageous properties	377:399	advantageous properties	377:399	However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation.
34551980	1	92	theme	biophysical	255:265	arg1	properties					267:276	the biological and biophysical properties	236:276	the biological and biophysical properties of proteins	236:288	As a common protein modification, asparagine-linked (N-linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins.
34770808	3	0	from	samples	561:567	arg1	determination					508:520	a high-resolution determination	490:520	a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D)	490:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	3	1	theme	bioanalytical	461:473	arg1	technique					475:483	the applied capillary electrophoresis bioanalytical technique	423:483	the applied capillary electrophoresis bioanalytical technique	423:483	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	3	2	theme	capillary	435:443	arg1	technique					475:483	the applied capillary electrophoresis bioanalytical technique	423:483	the applied capillary electrophoresis bioanalytical technique	423:483	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	4	3	theme	samples	747:753	arg1	glycoproteins					726:738	the glycoproteins	722:738	the glycoproteins of the samples	722:753	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	7	4	theme	significant	1354:1364	arg1	changes					1366:1372	significant changes	1354:1372	significant changes between the untreated/treated type 2 diabetic and control samples	1354:1438	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	6	5	theme	whole	1081:1085	arg1	samples					1093:1099	whole blood samples	1081:1099	whole blood samples from the diabetic patients	1081:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	4	6	attach	linked	679:684	arg1	hIgG					703:706	hIgG	703:706	hIgG in the blood	703:719	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	4	6	attach	linked	679:684	arg2	oligosaccharides					661:676	these complex oligosaccharides	647:676	these complex oligosaccharides	647:676	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	2	7	theme	reliable	226:233	arg1	methods					246:252	rapid, simple, and reliable analytical methods	207:252	rapid, simple, and reliable analytical methods that can detect the disease at an early stage	207:298	Thus, there is a need to find rapid, simple, and reliable analytical methods that can detect the disease at an early stage.
34770808	9	8	theme	specific	1729:1736	arg1	profiles					1758:1765	specific IgG N-glycosylation profiles	1729:1765	specific IgG N-glycosylation profiles in T2D	1729:1772	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	4	9	theme	profile	624:630	arg1	information					632:642	the profile information	620:642	the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood	620:719	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	3	10	theme	human	549:553	arg1	samples					561:567	human blood samples	549:567	human blood samples of patients with type 2 diabetes (T2D)	549:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	1	11	theme	diagnosing	122:131	arg1	challenge					166:174	a great challenge	158:174	a great challenge	158:174	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	1	11	theme	diagnosing	122:131	arg1	T2D					150:152	T2D	150:152	T2D	150:152	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	1	11	theme	diagnosing	122:131	arg1	diabetes					140:147	diagnosing type 2 diabetes	122:147	diagnosing type 2 diabetes (T2D)	122:153	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	9	12	theme	N-glycosylation	1742:1756	arg1	profiles					1758:1765	specific IgG N-glycosylation profiles	1729:1765	specific IgG N-glycosylation profiles in T2D	1729:1772	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	1	13	theme	great	160:164	arg1	challenge					166:174	a great challenge	158:174	a great challenge	158:174	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	1	13	theme	great	160:164	arg1	diabetes					140:147	diagnosing type 2 diabetes	122:147	diagnosing type 2 diabetes (T2D)	122:153	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	7	14	theme	N-glycan	1271:1278	arg1	glycobiomarkers					1320:1334	potential glycobiomarkers	1310:1334	potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples	1310:1438	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	7	14	theme	N-glycan	1271:1278	arg1	structures					1280:1289	two N-glycan structures	1267:1289	two N-glycan structures	1267:1289	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	7	15	theme	subtle	1166:1171	arg1	differences					1173:1183	subtle differences	1166:1183	subtle differences between the N-glycan profiles of the diabetic and control samples	1166:1249	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	3	16	theme	profile	538:544	arg1	determination					508:520	a high-resolution determination	490:520	a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D)	490:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	0	17	theme	Capillary	63:71	arg1	Electrophoresis					73:87	Capillary Electrophoresis	63:87	Capillary Electrophoresis	63:87	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	8	18	theme	oligosaccharide	1468:1482	arg1	profiles					1484:1491	the resulting oligosaccharide profiles	1454:1491	the resulting oligosaccharide profiles	1454:1491	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	8	19	from	profile	1673:1679	arg1	blood					1688:1692	the blood	1684:1692	the blood	1684:1692	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	3	20	from	profile	538:544	arg1	samples					561:567	human blood samples	549:567	human blood samples of patients with type 2 diabetes (T2D)	549:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	0	21	theme	Preliminary	92:102	arg1	Study					104:108	A Preliminary Study	90:108	A Preliminary Study	90:108	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	7	22	dep	diabetic	1222:1229	arg1	samples					1243:1249	samples	1243:1249	samples	1243:1249	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	8	23	theme	relevant	1505:1512	arg1	information					1514:1524	clinically relevant information	1494:1524	clinically relevant information	1494:1524	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	0	24	theme	N-Glycosylation	0:14	arg1	Profiling					16:24	N-Glycosylation Profiling	0:24	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis	0:87	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	9	25	theme	pathophysiological	1818:1835	arg1	processes					1837:1845	inflammatory pathophysiological processes	1805:1845	inflammatory pathophysiological processes	1805:1845	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	4	26	theme	complex	653:659	arg1	oligosaccharides					661:676	these complex oligosaccharides	647:676	these complex oligosaccharides	647:676	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	3	27	from	determination	508:520	arg1	samples					561:567	human blood samples	549:567	human blood samples of patients with type 2 diabetes (T2D)	549:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	3	28	theme	sample	361:366	arg1	options					379:385	sample collection options	361:385	sample collection options	361:385	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	3	29	theme	applied	427:433	arg1	technique					475:483	the applied capillary electrophoresis bioanalytical technique	423:483	the applied capillary electrophoresis bioanalytical technique	423:483	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	6	30	theme	separation	954:963	arg1	optimization					975:986	separation parameter optimization	954:986	separation parameter optimization	954:986	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	3	31	theme	patients	572:579	arg1	samples					561:567	human blood samples	549:567	human blood samples of patients with type 2 diabetes (T2D)	549:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	0	32	theme	Blood	35:39	arg1	Profiling					16:24	N-Glycosylation Profiling	0:24	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis	0:87	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	5	33	theme	laser-induced	910:922	arg1	detection					937:945	laser-induced fluorescence detection	910:945	laser-induced fluorescence detection	910:945	The resulting samples were analyzed by capillary electrophoresis, with laser-induced fluorescence detection.
34770808	7	34	theme	control	1235:1241	arg1	profiles					1206:1213	the N-glycan profiles	1193:1213	the N-glycan profiles of the diabetic and control samples	1193:1249	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	3	35	theme	sample	388:393	arg1	conditions					407:416	sample preparation conditions	388:416	sample preparation conditions	388:416	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	0	36	theme	Type	44:47	arg1	Diabetes					51:58	Type 2 Diabetes	44:58	Type 2 Diabetes	44:58	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	6	37	theme	N-glycan	1059:1066	arg1	profiling					1068:1076	efficient N-glycan profiling	1049:1076	efficient N-glycan profiling of whole blood samples from the diabetic patients	1049:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	3	38	theme	options	379:385	arg1	importance					347:356	the importance	343:356	the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D)	343:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	5	39	theme	capillary	878:886	arg1	electrophoresis					888:902	capillary electrophoresis	878:902	capillary electrophoresis	878:902	The resulting samples were analyzed by capillary electrophoresis, with laser-induced fluorescence detection.
34770808	8	40	theme	untreated	1578:1586	arg1	patients					1637:1644	the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients	1574:1644	the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood	1574:1692	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	3	41	theme	type	586:589	arg1	T2D					603:605	T2D	603:605	T2D	603:605	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	3	41	theme	type	586:589	arg1	diabetes					593:600	type 2 diabetes	586:600	type 2 diabetes (T2D)	586:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	8	42	theme	N-glycan	1664:1671	arg1	profile					1673:1679	the N-glycan profile	1660:1679	the N-glycan profile in the blood	1660:1692	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	7	43	theme	N-glycan	1197:1204	arg1	profiles					1206:1213	the N-glycan profiles	1193:1213	the N-glycan profiles of the diabetic and control samples	1193:1249	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	3	44	theme	conditions	407:416	arg1	importance					347:356	the importance	343:356	the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D)	343:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	6	45	theme	electrophoresis	1003:1017	arg1	technique					1019:1027	the capillary electrophoresis technique	989:1027	the capillary electrophoresis technique	989:1027	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	8	46	theme	diabetic	1628:1635	arg1	patients					1637:1644	the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients	1574:1644	the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood	1574:1692	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	3	47	theme	electrophoresis	445:459	arg1	technique					475:483	the applied capillary electrophoresis bioanalytical technique	423:483	the applied capillary electrophoresis bioanalytical technique	423:483	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	6	48	theme	samples	1093:1099	arg1	profiling					1068:1076	efficient N-glycan profiling	1049:1076	efficient N-glycan profiling of whole blood samples from the diabetic patients	1049:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	6	49	theme	diabetic	1110:1117	arg1	patients					1119:1126	the diabetic patients	1106:1126	the diabetic patients	1106:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	2	50	theme	simple	214:219	arg1	methods					246:252	rapid, simple, and reliable analytical methods	207:252	rapid, simple, and reliable analytical methods that can detect the disease at an early stage	207:298	Thus, there is a need to find rapid, simple, and reliable analytical methods that can detect the disease at an early stage.
34770808	9	51	theme	drug	1859:1862	arg1	targets					1864:1870	drug targets	1859:1870	drug targets	1859:1870	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	6	52	theme	blood	1087:1091	arg1	samples					1093:1099	whole blood samples	1081:1099	whole blood samples from the diabetic patients	1081:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	2	53	theme	analytical	235:244	arg1	methods					246:252	rapid, simple, and reliable analytical methods	207:252	rapid, simple, and reliable analytical methods that can detect the disease at an early stage	207:298	Thus, there is a need to find rapid, simple, and reliable analytical methods that can detect the disease at an early stage.
34770808	4	54	gly	glycoproteins	726:738	arg1	glycoproteins					726:738	the glycoproteins	722:738	the glycoproteins of the samples	722:753	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	7	55	theme	diabetic	1222:1229	arg1	profiles					1206:1213	the N-glycan profiles	1193:1213	the N-glycan profiles of the diabetic and control samples	1193:1249	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	3	56	with	patients	572:579	arg1	T2D					603:605	T2D	603:605	T2D	603:605	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	3	56	with	patients	572:579	arg1	diabetes					593:600	type 2 diabetes	586:600	type 2 diabetes (T2D)	586:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	4	57	theme	sufficient	805:814	arg1	yield					816:820	sufficient yield	805:820	sufficient yield	805:820	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	8	58	from	changes	1649:1655	arg1	profile					1673:1679	the N-glycan profile	1660:1679	the N-glycan profile in the blood	1660:1692	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	3	59	theme	high-resolution	492:506	arg1	determination					508:520	a high-resolution determination	490:520	a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D)	490:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	7	60	theme	potential	1310:1318	arg1	glycobiomarkers					1320:1334	potential glycobiomarkers	1310:1334	potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples	1310:1438	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	7	60	theme	potential	1310:1318	arg1	structures					1280:1289	two N-glycan structures	1267:1289	two N-glycan structures	1267:1289	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	8	61	from	patients	1637:1644	arg1	changes					1649:1655	changes	1649:1655	changes in the N-glycan profile in the blood	1649:1692	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	2	62	theme	rapid	207:211	arg1	methods					246:252	rapid, simple, and reliable analytical methods	207:252	rapid, simple, and reliable analytical methods that can detect the disease at an early stage	207:298	Thus, there is a need to find rapid, simple, and reliable analytical methods that can detect the disease at an early stage.
34770808	3	63	theme	technique	475:483	arg1	importance					347:356	the importance	343:356	the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D)	343:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	9	64	theme	IgG	1738:1740	arg1	profiles					1758:1765	specific IgG N-glycosylation profiles	1729:1765	specific IgG N-glycosylation profiles in T2D	1729:1772	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	5	65	theme	resulting	843:851	arg1	samples					853:859	The resulting samples	839:859	The resulting samples	839:859	The resulting samples were analyzed by capillary electrophoresis, with laser-induced fluorescence detection.
34770808	3	66	theme	N-glycan	529:536	arg1	profile					538:544	the N-glycan profile	525:544	the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D)	525:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	4	67	from	hIgG	703:706	arg1	blood					715:719	the blood	711:719	the blood	711:719	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	1	68	theme	type	133:136	arg1	challenge					166:174	a great challenge	158:174	a great challenge	158:174	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	1	68	theme	type	133:136	arg1	T2D					150:152	T2D	150:152	T2D	150:152	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	1	68	theme	type	133:136	arg1	diabetes					140:147	diagnosing type 2 diabetes	122:147	diagnosing type 2 diabetes (T2D)	122:153	Currently, diagnosing type 2 diabetes (T2D) is a great challenge.
34770808	8	69	theme	resulting	1458:1466	arg1	profiles					1484:1491	the resulting oligosaccharide profiles	1454:1491	the resulting oligosaccharide profiles	1454:1491	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	0	70	from	Profiling	16:24	arg1	Diabetes					51:58	Type 2 Diabetes	44:58	Type 2 Diabetes	44:58	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	0	71	dep	Study	104:108	arg1	Profiling					16:24	N-Glycosylation Profiling	0:24	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis	0:87	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	4	72	theme	oligosaccharides	661:676	arg1	information					632:642	the profile information	620:642	the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood	620:719	To achieve the profile information of these complex oligosaccharides, linked by asparagine to hIgG in the blood, the glycoproteins of the samples needed to be cleaved, labelled, and purified with sufficient yield and selectivity.
34770808	6	73	theme	capillary	993:1001	arg1	technique					1019:1027	the capillary electrophoresis technique	989:1027	the capillary electrophoresis technique	989:1027	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	6	74	from	patients	1119:1126	arg1	samples					1093:1099	whole blood samples	1081:1099	whole blood samples from the diabetic patients	1081:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	6	74	from	patients	1119:1126	arg1	profiling					1068:1076	efficient N-glycan profiling	1049:1076	efficient N-glycan profiling of whole blood samples from the diabetic patients	1049:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	9	75	theme	inflammatory	1805:1816	arg1	processes					1837:1845	inflammatory pathophysiological processes	1805:1845	inflammatory pathophysiological processes	1805:1845	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	0	76	theme	Human	29:33	arg1	Blood					35:39	Human Blood	29:39	Human Blood	29:39	N-Glycosylation Profiling of Human Blood in Type 2 Diabetes by Capillary Electrophoresis: A Preliminary Study.
34770808	6	77	theme	parameter	965:973	arg1	optimization					975:986	separation parameter optimization	954:986	separation parameter optimization	954:986	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	3	78	theme	collection	368:377	arg1	options					379:385	sample collection options	361:385	sample collection options	361:385	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	3	79	theme	blood	555:559	arg1	samples					561:567	human blood samples	549:567	human blood samples of patients with type 2 diabetes (T2D)	549:606	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	7	80	dep	diabetic	1411:1418	arg1	samples					1432:1438	samples	1432:1438	samples	1432:1438	Our results revealed that there were subtle differences between the N-glycan profiles of the diabetic and control samples; in particular, two N-glycan structures were identified as potential glycobiomarkers that could reveal significant changes between the untreated/treated type 2 diabetic and control samples.
34770808	5	81	theme	fluorescence	924:935	arg1	detection					937:945	laser-induced fluorescence detection	910:945	laser-induced fluorescence detection	910:945	The resulting samples were analyzed by capillary electrophoresis, with laser-induced fluorescence detection.
34770808	3	82	theme	work	317:320	arg1	aim					305:307	The aim	301:307	The aim of this work	301:320	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	6	83	from	profiling	1068:1076	arg1	patients					1119:1126	the diabetic patients	1106:1126	the diabetic patients	1106:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	3	84	theme	preparation	395:405	arg1	conditions					407:416	sample preparation conditions	388:416	sample preparation conditions	388:416	The aim of this work was to shed light on the importance of sample collection options, sample preparation conditions, and the applied capillary electrophoresis bioanalytical technique, for a high-resolution determination of the N-glycan profile in human blood samples of patients with type 2 diabetes (T2D).
34770808	6	85	theme	efficient	1049:1057	arg1	profiling					1068:1076	efficient N-glycan profiling	1049:1076	efficient N-glycan profiling of whole blood samples from the diabetic patients	1049:1126	After separation parameter optimization, the capillary electrophoresis technique was implemented for efficient N-glycan profiling of whole blood samples from the diabetic patients.
34770808	9	86	from	profiles	1758:1765	arg1	T2D					1770:1772	T2D	1770:1772	T2D	1770:1772	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	9	86	from	profiles	1758:1765	arg1	information					1712:1722	the information	1708:1722	the information from specific IgG N-glycosylation profiles in T2D	1708:1772	In addition, the information from specific IgG N-glycosylation profiles in T2D could shed light on underlying inflammatory pathophysiological processes and lead to drug targets.
34770808	8	87	theme	reductase-inhibitor-treated	1600:1626	arg1	patients					1637:1644	the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients	1574:1644	the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood	1574:1692	By analyzing the resulting oligosaccharide profiles, clinically relevant information was obtained, revealing the differences between the untreated and HMG-CoA reductase-inhibitor-treated diabetic patients on changes in the N-glycan profile in the blood.
34770808	2	88	theme	early	288:292	arg1	stage					294:298	an early stage	285:298	an early stage	285:298	Thus, there is a need to find rapid, simple, and reliable analytical methods that can detect the disease at an early stage.
33347638	10	0	theme	biotin-MPA	2152:2161	arg1	pair					2144:2147	the pair	2140:2147	the pair of biotin-MPA and streptavidin-phycoerythrin	2140:2192	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	12	1	dep	CONCLUSION	2442:2451	arg1	indicator					2565:2573	a complementary indicator	2549:2573	a complementary indicator for the malignancy of prostate cancer	2549:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	12	1	dep	CONCLUSION	2442:2451	arg1	level					2536:2540	the serum O-glycosylated clusterin level	2501:2540	the serum O-glycosylated clusterin level	2501:2540	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	4	2	theme	serum	557:561	arg1	proteins					563:570	patients' serum proteins	547:570	patients' serum proteins	547:570	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	7	3	theme	microarray	1116:1125	arg1	analyses					1127:1134	RESULTS Lectin microarray analyses	1101:1134	RESULTS Lectin microarray analyses	1101:1134	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	11	4	theme	MPA-recognized	2275:2288	arg1	clusterin					2290:2298	MPA-recognized clusterin	2275:2298	MPA-recognized clusterin	2275:2298	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	12	5	gly	O-glycosylated	2511:2524	arg1	indicator					2565:2573	a complementary indicator	2549:2573	a complementary indicator for the malignancy of prostate cancer	2549:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	12	5	gly	O-glycosylated	2511:2524	arg1	level					2536:2540	the serum O-glycosylated clusterin level	2501:2540	the serum O-glycosylated clusterin level	2501:2540	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	7	6	theme	O-glycosylated	1395:1408	arg1	proteins					1410:1417	O-glycosylated proteins	1395:1417	O-glycosylated proteins	1395:1417	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	7	7	theme	RESULTS	1101:1107	arg1	analyses					1127:1134	RESULTS Lectin microarray analyses	1101:1134	RESULTS Lectin microarray analyses	1101:1134	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	5	8	theme	mass	872:875	arg1	spectrometry					877:888	quantitative mass spectrometry	859:888	quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling	859:990	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	7	9	from	abundant	1428:1435	arg1	sera					1440:1443	sera	1440:1443	sera from patients with prostate cancer	1440:1478	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	10	10	theme	streptavidin-phycoerythrin	2167:2192	arg1	pair					2144:2147	the pair	2140:2147	the pair of biotin-MPA and streptavidin-phycoerythrin	2140:2192	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	7	11	contain	had	1190:1192	arg1	sera					1150:1153	sera	1150:1153	sera from patients with prostate cancer	1150:1188	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	7	11	contain	had	1190:1192	arg2	affinity					1203:1210	a higher affinity	1194:1210	a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin,	1194:1292	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	2	12	theme	prostate	292:299	arg1	cancer					301:306	highly suspicious prostate cancer	274:306	highly suspicious prostate cancer	274:306	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	7	13	from	sera	1440:1443	arg1	abundant					1428:1435	abundant	1428:1435	abundant	1428:1435	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	12	14	theme	complementary	2551:2563	arg1	indicator					2565:2573	a complementary indicator	2549:2573	a complementary indicator for the malignancy of prostate cancer	2549:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	12	14	theme	complementary	2551:2563	arg1	level					2536:2540	the serum O-glycosylated clusterin level	2501:2540	the serum O-glycosylated clusterin level	2501:2540	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	4	15	theme	microarray	607:616	arg1	analyses					618:625	comprehensive lectin microarray analyses	586:625	comprehensive lectin microarray analyses	586:625	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	10	16	theme	total	1994:1998	arg1	clusterin					2006:2014	total serum clusterin	1994:2014	total serum clusterin	1994:2014	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	2	17	theme	highly	274:279	arg1	cancer					301:306	highly suspicious prostate cancer	274:306	highly suspicious prostate cancer	274:306	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	7	18	from	patients	1450:1457	arg1	sera					1440:1443	sera	1440:1443	sera from patients with prostate cancer	1440:1478	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	4	19	from	cancer	685:690	arg1	sera					666:669	sera	666:669	sera from prostate cancer and benign prostatic diseases	666:720	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	7	20	theme	prostatic	1339:1347	arg1	diseases					1349:1356	benign prostatic diseases	1332:1356	benign prostatic diseases	1332:1356	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	2	21	theme	frequent	207:214	arg1	occurrence					216:225	The frequent occurrence	203:225	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer	203:306	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	5	22	theme	isobaric	923:930	arg1	tag					932:934	isobaric tag	923:934	isobaric tag for relative and absolute quantitation (iTRAQ) labeling	923:990	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	4	23	theme	prostatic	703:711	arg1	diseases					713:720	benign prostatic diseases	696:720	benign prostatic diseases	696:720	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	5	24	theme	absolute	953:960	arg1	 labeling					982:990	relative and absolute quantitation (iTRAQ) labeling	940:990	relative and absolute quantitation (iTRAQ) labeling	940:990	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	6	25	theme	new	1019:1021	arg1	assay					1023:1027	a new assay	1017:1027	a new assay to quantify a candidate glycoprotein with the newly identified glycans	1017:1098	Finally, we constructed a new assay to quantify a candidate glycoprotein with the newly identified glycans.
33347638	10	26	theme	antibody-immobilized	2053:2072	arg1	beads					2074:2078	anti-clusterin antibody-immobilized beads	2038:2078	anti-clusterin antibody-immobilized beads	2038:2078	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	7	27	with	patients	1318:1325	arg1	diseases					1349:1356	benign prostatic diseases	1332:1356	benign prostatic diseases	1332:1356	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	2	28	theme	PSA	234:236	arg1	values					238:243	low PSA values	230:243	low PSA values (<10 ng/ml)	230:255	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	2	28	theme	PSA	234:236	arg1	<10 ng/ml					246:254	<10 ng/ml	246:254	<10 ng/ml	246:254	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	2	29	with	patients	260:267	arg1	cancer					301:306	highly suspicious prostate cancer	274:306	highly suspicious prostate cancer	274:306	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	11	30	theme	clusterin	2290:2298	arg1	level					2266:2270	the corresponding serum level	2242:2270	the corresponding serum level of MPA-recognized clusterin determined by this assay	2242:2323	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	11	30	theme	clusterin	2290:2298	arg1	beneficial					2329:2338	beneficial	2329:2338	beneficial	2329:2338	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	4	31	theme	prostate	676:683	arg1	cancer					685:690	prostate cancer	676:690	prostate cancer	676:690	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	5	32	theme	serum	752:756	arg1	proteins					758:765	candidate serum proteins	742:765	candidate serum proteins	742:765	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	4	33	dep	METHODS	497:503	arg1	focused					508:514	focused	508:514	focused on the glycosylation status of patients' serum proteins	508:570	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	4	33	dep	METHODS	497:503	arg1	conducted					576:584	conducted	576:584	conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases	576:720	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	9	34	theme	benign	1857:1862	arg1	diseases					1874:1881	benign prostatic diseases	1857:1881	benign prostatic diseases	1857:1881	It was found that the ACA- and MPA-recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases.
33347638	7	35	from	patients	1160:1167	arg1	sera					1150:1153	sera	1150:1153	sera from patients with prostate cancer	1150:1188	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	5	36	theme	quantitation	962:973	arg1	 labeling					982:990	relative and absolute quantitation (iTRAQ) labeling	940:990	relative and absolute quantitation (iTRAQ) labeling	940:990	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	0	37	theme	cancer	87:92	arg1	stages					68:73	early stages	62:73	early stages of prostate cancer	62:92	O-glycosylated clusterin as a sensitive marker for diagnosing early stages of prostate cancer.
33347638	5	38	theme	iTRAQ	976:980	arg1	 labeling					982:990	relative and absolute quantitation (iTRAQ) labeling	940:990	relative and absolute quantitation (iTRAQ) labeling	940:990	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	2	39	from	occurrence	216:225	arg1	patients					260:267	patients	260:267	patients with highly suspicious prostate cancer	260:306	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	7	40	theme	higher	1196:1201	arg1	affinity					1203:1210	a higher affinity	1194:1210	a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin,	1194:1292	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	2	41	theme	examinations	358:369	arg1	accuracy					337:344	the accuracy	333:344	the accuracy of clinical examinations	333:369	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	12	42	theme	serum	2505:2509	arg1	indicator					2565:2573	a complementary indicator	2549:2573	a complementary indicator for the malignancy of prostate cancer	2549:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	12	42	theme	serum	2505:2509	arg1	level					2536:2540	the serum O-glycosylated clusterin level	2501:2540	the serum O-glycosylated clusterin level	2501:2540	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	7	43	theme	prostate	1174:1181	arg1	cancer					1183:1188	prostate cancer	1174:1188	prostate cancer	1174:1188	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	1	44	theme	Prostate-specific	106:122	arg1	PSA					133:135	PSA	133:135	PSA	133:135	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	1	44	theme	Prostate-specific	106:122	arg1	marker					175:180	the most popular diagnostic marker	147:180	the most popular diagnostic marker for prostate cancer	147:200	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	1	44	theme	Prostate-specific	106:122	arg1	antigen					124:130	BACKGROUND Prostate-specific antigen	95:130	BACKGROUND Prostate-specific antigen (PSA)	95:136	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	4	45	theme	glycosylation	523:535	arg1	status					537:542	the glycosylation status	519:542	the glycosylation status of patients' serum proteins	519:570	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	3	46	theme	better	411:416	arg1	resolution					418:427	a better resolution	409:427	a better resolution for diagnosing prostate cancer to overcome the disadvantage of PSA	409:494	The aim of this study was to develop a better resolution for diagnosing prostate cancer to overcome the disadvantage of PSA.
33347638	1	47	theme	popular	156:162	arg1	marker					175:180	the most popular diagnostic marker	147:180	the most popular diagnostic marker for prostate cancer	147:200	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	1	47	theme	popular	156:162	arg1	antigen					124:130	BACKGROUND Prostate-specific antigen	95:130	BACKGROUND Prostate-specific antigen (PSA)	95:136	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	0	48	theme	sensitive	30:38	arg1	marker					40:45	a sensitive marker	28:45	a sensitive marker for diagnosing early stages of prostate cancer	28:92	O-glycosylated clusterin as a sensitive marker for diagnosing early stages of prostate cancer.
33347638	7	49	theme	MPA	1281:1283	arg1	lectin					1286:1291	Maclura pomifera (MPA) lectin	1263:1291	Maclura pomifera (MPA) lectin	1263:1291	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	7	49	theme	MPA	1281:1283	arg1	Jacalin					1216:1222	Jacalin	1216:1222	Jacalin	1216:1222	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	9	50	theme	prostatic	1864:1872	arg1	diseases					1874:1881	benign prostatic diseases	1857:1881	benign prostatic diseases	1857:1881	It was found that the ACA- and MPA-recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases.
33347638	8	51	theme	biotin-ACA/and	1563:1576	arg1	beads					1623:1627	biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1563:1627	serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1487:1627	Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry.
33347638	7	52	theme	caudatus	1236:1243	arg1	lectin					1251:1256	Amaranthus caudatus (ACA) lectin	1225:1256	Amaranthus caudatus (ACA) lectin	1225:1256	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	7	52	theme	caudatus	1236:1243	arg1	Jacalin					1216:1222	Jacalin	1216:1222	Jacalin	1216:1222	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	5	53	theme	glycan	787:792	arg1	structures					794:803	characteristic glycan structures	772:803	characteristic glycan structures using lectin-immobilized beads	772:834	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	7	54	theme	pomifera	1271:1278	arg1	lectin					1286:1291	Maclura pomifera (MPA) lectin	1263:1291	Maclura pomifera (MPA) lectin	1263:1291	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	7	54	theme	pomifera	1271:1278	arg1	Jacalin					1216:1222	Jacalin	1216:1222	Jacalin	1216:1222	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	11	55	theme	benign	2416:2421	arg1	disease					2433:2439	benign prostatic disease	2416:2439	benign prostatic disease	2416:2439	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	8	56	theme	magnetic	1614:1621	arg1	beads					1623:1627	biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1563:1627	serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1487:1627	Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry.
33347638	6	57	gly	glycoprotein	1053:1064	arg1	glycoprotein					1053:1064	a candidate glycoprotein	1041:1064	a candidate glycoprotein with the newly identified glycans	1041:1098	Finally, we constructed a new assay to quantify a candidate glycoprotein with the newly identified glycans.
33347638	3	58	theme	prostate	444:451	arg1	cancer					453:458	prostate cancer	444:458	prostate cancer	444:458	The aim of this study was to develop a better resolution for diagnosing prostate cancer to overcome the disadvantage of PSA.
33347638	11	59	with	patients	2363:2370	arg1	cancer					2386:2391	prostate cancer	2377:2391	prostate cancer	2377:2391	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	1	60	theme	diagnostic	164:173	arg1	marker					175:180	the most popular diagnostic marker	147:180	the most popular diagnostic marker for prostate cancer	147:200	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	1	60	theme	diagnostic	164:173	arg1	antigen					124:130	BACKGROUND Prostate-specific antigen	95:130	BACKGROUND Prostate-specific antigen (PSA)	95:136	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	11	61	theme	serum	2260:2264	arg1	level					2266:2270	the corresponding serum level	2242:2270	the corresponding serum level of MPA-recognized clusterin determined by this assay	2242:2323	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	11	61	theme	serum	2260:2264	arg1	beneficial					2329:2338	beneficial	2329:2338	beneficial	2329:2338	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	7	62	theme	prostate	1464:1471	arg1	cancer					1473:1478	prostate cancer	1464:1478	prostate cancer	1464:1478	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	5	63	theme	candidate	742:750	arg1	proteins					758:765	candidate serum proteins	742:765	candidate serum proteins	742:765	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	11	64	theme	PSA	2200:2202	arg1	values					2204:2209	PSA values	2200:2209	PSA values	2200:2209	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	6	65	theme	identified	1081:1090	arg1	glycans					1092:1098	the newly identified glycans	1071:1098	the newly identified glycans	1071:1098	Finally, we constructed a new assay to quantify a candidate glycoprotein with the newly identified glycans.
33347638	12	66	theme	PSA	2457:2459	arg1	values					2461:2466	PSA values	2457:2466	PSA values that measure less than 10 ng/ml	2457:2498	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	10	67	theme	Luminex-based	1927:1939	arg1	assay					1941:1945	a Luminex-based assay	1925:1945	a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin	1925:2192	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	7	68	theme	Lectin	1109:1114	arg1	analyses					1127:1134	RESULTS Lectin microarray analyses	1101:1134	RESULTS Lectin microarray analyses	1101:1134	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	11	69	with	patients	2402:2409	arg1	disease					2433:2439	benign prostatic disease	2416:2439	benign prostatic disease	2416:2439	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	12	70	theme	prostate	2597:2604	arg1	cancer					2606:2611	prostate cancer	2597:2611	prostate cancer	2597:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	5	71	theme	quantitative	859:870	arg1	spectrometry					877:888	quantitative mass spectrometry	859:888	quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling	859:990	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	7	72	gly	O-glycosylated	1395:1408	arg1	proteins					1410:1417	O-glycosylated proteins	1395:1417	O-glycosylated proteins	1395:1417	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	9	73	from	cancer	1825:1830	arg1	sera					1806:1809	patients' sera	1796:1809	patients' sera from prostate cancer	1796:1830	It was found that the ACA- and MPA-recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases.
33347638	7	74	with	patients	1160:1167	arg1	cancer					1183:1188	prostate cancer	1174:1188	prostate cancer	1174:1188	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	12	75	theme	cancer	2606:2611	arg1	malignancy					2583:2592	the malignancy	2579:2592	the malignancy of prostate cancer	2579:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	10	76	theme	O-glycosylated	1959:1972	arg1	clusterin					1974:1982	O-glycosylated clusterin	1959:1982	O-glycosylated clusterin	1959:1982	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	10	77	theme	serum	2000:2004	arg1	clusterin					2006:2014	total serum clusterin	1994:2014	total serum clusterin	1994:2014	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	1	78	theme	prostate	186:193	arg1	cancer					195:200	prostate cancer	186:200	prostate cancer	186:200	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	11	79	theme	prostate	2377:2384	arg1	cancer					2386:2391	prostate cancer	2377:2391	prostate cancer	2377:2391	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	4	80	theme	lectin	600:605	arg1	analyses					618:625	comprehensive lectin microarray analyses	586:625	comprehensive lectin microarray analyses	586:625	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	2	81	theme	low	230:232	arg1	values					238:243	low PSA values	230:243	low PSA values (<10 ng/ml)	230:255	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	2	81	theme	low	230:232	arg1	<10 ng/ml					246:254	<10 ng/ml	246:254	<10 ng/ml	246:254	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	9	82	theme	ACA-	1739:1742	arg1	clusterin					1765:1773	the ACA- and MPA-recognizable clusterin	1735:1773	the ACA- and MPA-recognizable clusterin	1735:1773	It was found that the ACA- and MPA-recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases.
33347638	7	83	theme	normal	1362:1367	arg1	subjects					1369:1376	normal subjects	1362:1376	normal subjects	1362:1376	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	12	84	theme	O-glycosylated	2511:2524	arg1	indicator					2565:2573	a complementary indicator	2549:2573	a complementary indicator for the malignancy of prostate cancer	2549:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	12	84	theme	O-glycosylated	2511:2524	arg1	level					2536:2540	the serum O-glycosylated clusterin level	2501:2540	the serum O-glycosylated clusterin level	2501:2540	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	9	85	theme	MPA-recognizable	1748:1763	arg1	clusterin					1765:1773	the ACA- and MPA-recognizable clusterin	1735:1773	the ACA- and MPA-recognizable clusterin	1735:1773	It was found that the ACA- and MPA-recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases.
33347638	2	86	dep	highly	274:279	arg1	suspicious					281:290	suspicious	281:290	suspicious	281:290	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	10	87	gly	O-glycosylated	1959:1972	arg1	clusterin					1974:1982	O-glycosylated clusterin	1959:1982	O-glycosylated clusterin	1959:1982	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	7	88	theme	benign	1332:1337	arg1	diseases					1349:1356	benign prostatic diseases	1332:1356	benign prostatic diseases	1332:1356	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	4	89	theme	benign	696:701	arg1	diseases					713:720	benign prostatic diseases	696:720	benign prostatic diseases	696:720	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	7	90	theme	Amaranthus	1225:1234	arg1	ACA					1246:1248	ACA	1246:1248	ACA	1246:1248	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	7	90	theme	Amaranthus	1225:1234	arg1	caudatus					1236:1243	Amaranthus caudatus	1225:1243	Amaranthus caudatus (ACA) lectin	1225:1256	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	2	91	theme	values	238:243	arg1	occurrence					216:225	The frequent occurrence	203:225	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer	203:306	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	8	92	gly	glycoproteins	1493:1505	arg1	glycoproteins					1493:1505	serum glycoproteins	1487:1505	serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1487:1627	Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry.
33347638	10	93	theme	anti-clusterin	2038:2051	arg1	beads					2074:2078	anti-clusterin antibody-immobilized beads	2038:2078	anti-clusterin antibody-immobilized beads	2038:2078	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	0	94	theme	prostate	78:85	arg1	cancer					87:92	prostate cancer	78:92	prostate cancer	78:92	O-glycosylated clusterin as a sensitive marker for diagnosing early stages of prostate cancer.
33347638	8	95	theme	serum	1487:1491	arg1	glycoproteins					1493:1505	serum glycoproteins	1487:1505	serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1487:1627	Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry.
33347638	10	96	theme	clusterin-associated	2090:2109	arg1	O-glycans					2111:2119	then clusterin-associated O-glycans	2085:2119	then clusterin-associated O-glycans	2085:2119	Following this discovery, we constructed a Luminex-based assay to quantify O-glycosylated clusterin, in which total serum clusterin was first captured on anti-clusterin antibody-immobilized beads, and then clusterin-associated O-glycans were determined by the pair of biotin-MPA and streptavidin-phycoerythrin.
33347638	9	97	theme	prostate	1816:1823	arg1	cancer					1825:1830	prostate cancer	1816:1830	prostate cancer	1816:1830	It was found that the ACA- and MPA-recognizable clusterin was more enriched in patients' sera from prostate cancer compared with those from benign prostatic diseases.
33347638	7	98	with	subjects	1369:1376	arg1	diseases					1349:1356	benign prostatic diseases	1332:1356	benign prostatic diseases	1332:1356	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	5	99	theme	relative	940:947	arg1	 labeling					982:990	relative and absolute quantitation (iTRAQ) labeling	940:990	relative and absolute quantitation (iTRAQ) labeling	940:990	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	11	100	theme	corresponding	2246:2258	arg1	level					2266:2270	the corresponding serum level	2242:2270	the corresponding serum level of MPA-recognized clusterin determined by this assay	2242:2323	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	11	100	theme	corresponding	2246:2258	arg1	beneficial					2329:2338	beneficial	2329:2338	beneficial	2329:2338	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	2	101	theme	clinical	349:356	arg1	examinations					358:369	clinical examinations	349:369	clinical examinations	349:369	The frequent occurrence of low PSA values (<10 ng/ml) in patients with highly suspicious prostate cancer, however, has undermined the accuracy of clinical examinations.
33347638	5	102	theme	lectin-immobilized	811:828	arg1	beads					830:834	lectin-immobilized beads	811:834	lectin-immobilized beads	811:834	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	4	103	from	diseases	713:720	arg1	sera					666:669	sera	666:669	sera from prostate cancer and benign prostatic diseases	666:720	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	1	104	theme	BACKGROUND	95:104	arg1	PSA					133:135	PSA	133:135	PSA	133:135	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	1	104	theme	BACKGROUND	95:104	arg1	marker					175:180	the most popular diagnostic marker	147:180	the most popular diagnostic marker for prostate cancer	147:200	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	1	104	theme	BACKGROUND	95:104	arg1	antigen					124:130	BACKGROUND Prostate-specific antigen	95:130	BACKGROUND Prostate-specific antigen (PSA)	95:136	BACKGROUND Prostate-specific antigen (PSA) has been the most popular diagnostic marker for prostate cancer.
33347638	6	105	theme	candidate	1043:1051	arg1	glycoprotein					1053:1064	a candidate glycoprotein	1041:1064	a candidate glycoprotein with the newly identified glycans	1041:1098	Finally, we constructed a new assay to quantify a candidate glycoprotein with the newly identified glycans.
33347638	6	106	with	glycoprotein	1053:1064	arg1	glycans					1092:1098	the newly identified glycans	1071:1098	the newly identified glycans	1071:1098	Finally, we constructed a new assay to quantify a candidate glycoprotein with the newly identified glycans.
33347638	8	107	theme	quantitative	1685:1696	arg1	spectrometry					1703:1714	quantitative mass spectrometry	1685:1714	quantitative mass spectrometry	1685:1714	Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry.
33347638	3	108	theme	study	388:392	arg1	aim					376:378	The aim	372:378	The aim of this study	372:392	The aim of this study was to develop a better resolution for diagnosing prostate cancer to overcome the disadvantage of PSA.
33347638	8	109	theme	biotin-MPA/streptavidin-immobilized	1578:1612	arg1	beads					1623:1627	biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1563:1627	serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads	1487:1627	Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry.
33347638	5	110	theme	characteristic	772:785	arg1	structures					794:803	characteristic glycan structures	772:803	characteristic glycan structures using lectin-immobilized beads	772:834	Next, we retrieved candidate serum proteins with characteristic glycan structures using lectin-immobilized beads and identified them by quantitative mass spectrometry using a technique referred to as isobaric tag for relative and absolute quantitation (iTRAQ) labeling.
33347638	0	111	theme	early	62:66	arg1	stages					68:73	early stages	62:73	early stages of prostate cancer	62:92	O-glycosylated clusterin as a sensitive marker for diagnosing early stages of prostate cancer.
33347638	7	112	theme	Maclura	1263:1269	arg1	lectin					1286:1291	Maclura pomifera (MPA) lectin	1263:1291	Maclura pomifera (MPA) lectin	1263:1291	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	7	112	theme	Maclura	1263:1269	arg1	Jacalin					1216:1222	Jacalin	1216:1222	Jacalin	1216:1222	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
33347638	12	113	theme	clusterin	2526:2534	arg1	indicator					2565:2573	a complementary indicator	2549:2573	a complementary indicator for the malignancy of prostate cancer	2549:2611	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	12	113	theme	clusterin	2526:2534	arg1	level					2536:2540	the serum O-glycosylated clusterin level	2501:2540	the serum O-glycosylated clusterin level	2501:2540	CONCLUSION For PSA values that measure less than 10 ng/ml, the serum O-glycosylated clusterin level can be a complementary indicator for the malignancy of prostate cancer.
33347638	11	114	theme	prostatic	2423:2431	arg1	disease					2433:2439	benign prostatic disease	2416:2439	benign prostatic disease	2416:2439	When PSA values registered less than 10 ng/ml, the corresponding serum level of MPA-recognized clusterin determined by this assay was beneficial for distinguishing the patients with prostate cancer from the patients with benign prostatic disease.
33347638	8	115	theme	mass	1698:1701	arg1	spectrometry					1703:1714	quantitative mass spectrometry	1685:1714	quantitative mass spectrometry	1685:1714	Then, serum glycoproteins preferentially adsorbed onto Jacalin-Agarose as well as biotin-ACA/and biotin-MPA/streptavidin-immobilized magnetic beads were isolated, labeled with iTRAQ, and identified using quantitative mass spectrometry.
33347638	4	116	theme	comprehensive	586:598	arg1	analyses					618:625	comprehensive lectin microarray analyses	586:625	comprehensive lectin microarray analyses	586:625	METHODS We focused on the glycosylation status of patients' serum proteins and conducted comprehensive lectin microarray analyses to characterize N- and O-glycans using sera from prostate cancer and benign prostatic diseases.
33347638	3	117	theme	PSA	492:494	arg1	disadvantage					476:487	the disadvantage	472:487	the disadvantage of PSA	472:494	The aim of this study was to develop a better resolution for diagnosing prostate cancer to overcome the disadvantage of PSA.
33347638	7	118	with	patients	1450:1457	arg1	cancer					1473:1478	prostate cancer	1464:1478	prostate cancer	1464:1478	RESULTS Lectin microarray analyses revealed that sera from patients with prostate cancer had a higher affinity for Jacalin, Amaranthus caudatus (ACA) lectin, and Maclura pomifera (MPA) lectin, compared with that from patients with benign prostatic diseases and normal subjects, suggesting that O-glycosylated proteins are more abundant in sera from patients with prostate cancer.
32535395	7	0	theme	many	1066:1069	arg1	granules					1098:1105	accumulated many highly glycosylated apical granules	1054:1105	accumulated many highly glycosylated apical granules	1054:1105	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	3	1	theme	glycoproteins	487:499	arg1	composition					464:474	glycan composition	457:474	glycan composition	457:474	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	3	1	theme	glycoproteins	487:499	arg1	distribution					440:451	distribution	440:451	distribution	440:451	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	9	2	theme	non-ciliated	1328:1339	arg1	cells					1341:1345	non-ciliated cells	1328:1345	non-ciliated cells	1328:1345	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	10	3	theme	fewer	1489:1493	arg1	termini					1507:1513	fewer fucosylated termini	1489:1513	fewer fucosylated termini	1489:1513	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	1	4	theme	direct	227:232	arg1	interaction					248:258	direct intercellular interaction	227:258	direct intercellular interaction between the trophectoderm and uterine epithelium	227:307	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
32535395	4	5	theme	lectin	753:758	arg1	histochemistry					760:773	lectin histochemistry	753:773	lectin histochemistry	753:773	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	2	6	theme	glycoprotein-rich	344:360	arg1	secretions					362:371	glycoprotein-rich secretions	344:371	glycoprotein-rich secretions	344:371	The embryo is, however, bathed in glycoprotein-rich secretions.
32535395	9	7	contain	had	1347:1349	arg1	cells					1341:1345	non-ciliated cells	1328:1345	non-ciliated cells	1328:1345	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	9	7	contain	had	1347:1349	arg2	few					1358:1360	few	1358:1360	few	1358:1360	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	12	8	theme	conceptus	1886:1894	arg1	presence					1872:1879	the presence	1868:1879	the presence of a conceptus	1868:1894	The data strongly suggests that glycoprotein production by luminal epithelial cells is influenced by the presence of a conceptus.
32535395	8	9	theme	fewer	1188:1192	arg1	granules					1204:1211	fewer secretory granules	1188:1211	fewer secretory granules	1188:1211	By Days 12 and 15 post-ovulation these cells were more cuboidal and some showed fewer secretory granules.
32535395	10	10	theme	more	1516:1519	arg1	residues					1544:1551	more N-acetyl galactosamine residues	1516:1551	more N-acetyl galactosamine residues	1516:1551	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	11	11	theme	striking	1712:1719	arg1	similarity					1721:1730	a striking similarity	1710:1730	a striking similarity to that of the blastocyst capsule	1710:1764	Glycosylation in ciliated cells on Days 12 and 15 of pregnancy showed a striking similarity to that of the blastocyst capsule.
32535395	5	12	theme	lumenal	791:797	arg1	cells					810:814	lumenal epithelial cells	791:814	lumenal epithelial cells	791:814	During estrus, lumenal epithelial cells were as truncated pyramids and mainly non-ciliated with glycosylated granules in the cytoplasm.
32535395	4	13	theme	Endometrial	609:619	arg1	biopsies					621:628	Endometrial biopsies	609:628	Endometrial biopsies	609:628	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	7	14	theme	lumenal	1014:1020	arg1	epithelium					1022:1031	the lumenal epithelium	1010:1031	the lumenal epithelium	1010:1031	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	1	15	theme	equine	165:170	arg1	embryo					172:177	the equine embryo	161:177	the equine embryo	161:177	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
32535395	10	16	gly	fucosylated	1495:1505	arg1	termini					1507:1513	fewer fucosylated termini	1489:1513	fewer fucosylated termini	1489:1513	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	10	17	theme	galactosamine	1530:1542	arg1	residues					1544:1551	more N-acetyl galactosamine residues	1516:1551	more N-acetyl galactosamine residues	1516:1551	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	7	18	theme	non-ciliated	988:999	arg1	days					967:970	Five days	962:970	Five days post-ovulation	962:985	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	7	18	theme	non-ciliated	988:999	arg1	cells					1001:1005	non-ciliated cells	988:1005	non-ciliated cells of the lumenal epithelium	988:1031	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	13	19	gly	glycoproteins	1997:2009	arg1	glycoproteins					1997:2009	epithelial secretory glycoproteins	1976:2009	epithelial secretory glycoproteins	1976:2009	We speculate that, as well as providing nourishment for the developing embryo, epithelial secretory glycoproteins may contribute components to the capsule, which develops only partially in embryos cultured in vitro.
32535395	7	20	theme	post-ovulation	972:985	arg1	days					967:970	Five days	962:970	Five days post-ovulation	962:985	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	7	20	theme	post-ovulation	972:985	arg1	cells					1001:1005	non-ciliated cells	988:1005	non-ciliated cells of the lumenal epithelium	988:1031	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	3	21	from	effect	552:557	arg1	glycosylation					575:587	glycosylation	575:587	glycosylation in the endometrium	575:606	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	0	22	theme	cell	49:52	arg1	glycosylation					54:66	cell glycosylation	49:66	cell glycosylation in the endometrium of the mare	49:97	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.
32535395	9	23	theme	marked	1217:1222	arg1	contrast					1224:1231	marked contrast	1217:1231	marked contrast	1217:1231	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	6	24	theme	few	948:950	arg1	granules					952:959	few granules	948:959	few granules	948:959	Occasional ciliated cells contained few granules.
32535395	13	25	theme	secretory	1987:1995	arg1	glycoproteins					1997:2009	epithelial secretory glycoproteins	1976:2009	epithelial secretory glycoproteins	1976:2009	We speculate that, as well as providing nourishment for the developing embryo, epithelial secretory glycoproteins may contribute components to the capsule, which develops only partially in embryos cultured in vitro.
32535395	12	26	theme	epithelial	1834:1843	arg1	cells					1845:1849	luminal epithelial cells	1826:1849	luminal epithelial cells	1826:1849	The data strongly suggests that glycoprotein production by luminal epithelial cells is influenced by the presence of a conceptus.
32535395	10	27	from	pregnancy	1425:1433	arg1	epithelium					1472:1481	the luminal and superficial gland epithelium	1438:1481	the luminal and superficial gland epithelium	1438:1481	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	0	28	gly	glycosylation	54:66	arg1	endometrium					75:85	the endometrium	71:85	the endometrium of the mare	71:97	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.
32535395	6	29	theme	Occasional	912:921	arg1	cells					932:936	Occasional ciliated cells	912:936	Occasional ciliated cells	912:936	Occasional ciliated cells contained few granules.
32535395	3	30	used	used	415:418	arg2	histochemistry					396:409	lectin histochemistry	389:409	lectin histochemistry	389:409	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	13	31	theme	developing	1957:1966	arg1	embryo					1968:1973	the developing embryo	1953:1973	the developing embryo	1953:1973	We speculate that, as well as providing nourishment for the developing embryo, epithelial secretory glycoproteins may contribute components to the capsule, which develops only partially in embryos cultured in vitro.
32535395	12	32	theme	glycoprotein	1799:1810	arg1	production					1812:1821	glycoprotein production	1799:1821	glycoprotein production by luminal epithelial cells	1799:1849	The data strongly suggests that glycoprotein production by luminal epithelial cells is influenced by the presence of a conceptus.
32535395	3	33	theme	lectin	389:394	arg1	histochemistry					396:409	lectin histochemistry	389:409	lectin histochemistry	389:409	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	1	34	theme	intercellular	234:246	arg1	interaction					248:258	direct intercellular interaction	227:258	direct intercellular interaction between the trophectoderm and uterine epithelium	227:307	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
32535395	1	35	theme	post-conception	115:129	arg1	6.5-7					109:113	Day 6.5-7	105:113	Day 6.5-7 post-conception until its loss around Day 22	105:158	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
32535395	4	36	theme	pregnancy	725:733	arg1	Days					707:710	Days 12 and 15	707:720	Days	707:710	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	10	37	theme	sialic	1592:1597	arg1	acid					1599:1602	sialic acid	1592:1602	sialic acid	1592:1602	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	0	38	theme	stage	24:28	arg1	influences					4:13	The influences	0:13	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.	0:98	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.
32535395	9	39	theme	ciliated	1270:1277	arg1	cells					1279:1283	the ciliated cells	1266:1283	the ciliated cells	1266:1283	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	9	40	from	cytoplasm	1376:1384	arg1	few					1358:1360	few	1358:1360	few	1358:1360	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	1	41	theme	trophectoderm	272:284	arg1	epithelium					298:307	the trophectoderm and uterine epithelium	268:307	epithelium	298:307	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
32535395	10	42	theme	luminal	1442:1448	arg1	epithelium					1472:1481	the luminal and superficial gland epithelium	1438:1481	the luminal and superficial gland epithelium	1438:1481	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	7	43	gly	glycosylated	1078:1089	arg1	granules					1098:1105	accumulated many highly glycosylated apical granules	1054:1105	accumulated many highly glycosylated apical granules	1054:1105	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	0	44	theme	pregnancy	34:42	arg1	influences					4:13	The influences	0:13	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.	0:98	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.
32535395	1	45	theme	uterine	290:296	arg1	epithelium					298:307	the trophectoderm and uterine epithelium	268:307	epithelium	298:307	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
32535395	10	46	from	reduction	1579:1587	arg1	structures					1628:1637	several other sugar structures	1608:1637	several other sugar structures	1608:1637	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	10	46	from	reduction	1579:1587	arg1	acid					1599:1602	sialic acid	1592:1602	sialic acid	1592:1602	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	11	47	theme	ciliated	1657:1664	arg1	cells					1666:1670	ciliated cells	1657:1670	ciliated cells	1657:1670	Glycosylation in ciliated cells on Days 12 and 15 of pregnancy showed a striking similarity to that of the blastocyst capsule.
32535395	10	48	theme	other	1616:1620	arg1	structures					1628:1637	several other sugar structures	1608:1637	several other sugar structures	1608:1637	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	5	49	from	granules	885:892	arg1	cytoplasm					901:909	the cytoplasm	897:909	the cytoplasm	897:909	During estrus, lumenal epithelial cells were as truncated pyramids and mainly non-ciliated with glycosylated granules in the cytoplasm.
32535395	9	50	from	few	1358:1360	arg1	cytoplasm					1376:1384	the apical cytoplasm	1365:1384	the apical cytoplasm	1365:1384	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	12	51	gly	glycoprotein	1799:1810	arg1	glycoprotein					1799:1810	glycoprotein production	1799:1821	glycoprotein production by luminal epithelial cells	1799:1849	The data strongly suggests that glycoprotein production by luminal epithelial cells is influenced by the presence of a conceptus.
32535395	9	52	theme	numerous	1306:1313	arg1	granules					1315:1322	numerous granules	1306:1322	numerous granules	1306:1322	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	3	53	dep	distribution	440:451	arg1	the					436:438	the	436:438	the	436:438	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	10	54	theme	superficial	1454:1464	arg1	epithelium					1472:1481	the luminal and superficial gland epithelium	1438:1481	the luminal and superficial gland epithelium	1438:1481	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	7	55	theme	accumulated	1054:1064	arg1	granules					1098:1105	accumulated many highly glycosylated apical granules	1054:1105	accumulated many highly glycosylated apical granules	1054:1105	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	3	56	theme	uterine	479:485	arg1	glycoproteins					487:499	uterine glycoproteins	479:499	uterine glycoproteins destined for secretion	479:522	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	10	57	theme	fucosylated	1495:1505	arg1	termini					1507:1513	fewer fucosylated termini	1489:1513	fewer fucosylated termini	1489:1513	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	4	58	from	mares	646:650	arg1	estrus					655:660	estrus	655:660	estrus	655:660	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	4	58	from	mares	646:650	arg1	15					719:720	15	719:720	15	719:720	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	4	58	from	mares	646:650	arg1	Days					666:669	Days 5, 8, 12 and 15	666:685	Days 5, 8, 12 and 15 of diestrus	666:697	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	4	58	from	mares	646:650	arg1	Days					707:710	Days 12 and 15	707:720	Days	707:710	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	7	59	theme	glycosylated	1078:1089	arg1	granules					1098:1105	accumulated many highly glycosylated apical granules	1054:1105	accumulated many highly glycosylated apical granules	1054:1105	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	10	60	theme	N-acetyl	1521:1528	arg1	residues					1544:1551	more N-acetyl galactosamine residues	1516:1551	more N-acetyl galactosamine residues	1516:1551	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	7	61	theme	epithelium	1022:1031	arg1	days					967:970	Five days	962:970	Five days post-ovulation	962:985	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	7	61	theme	epithelium	1022:1031	arg1	cells					1001:1005	non-ciliated cells	988:1005	non-ciliated cells of the lumenal epithelium	988:1031	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	3	62	theme	local	546:550	arg1	effect					552:557	the local effect	542:557	the local effect of an embryo on glycosylation in the endometrium	542:606	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	3	63	gly	glycosylation	575:587	arg1	endometrium					596:606	the endometrium	592:606	the endometrium	592:606	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	5	64	with	non-ciliated	854:865	arg1	granules					885:892	glycosylated granules	872:892	glycosylated granules in the cytoplasm	872:909	During estrus, lumenal epithelial cells were as truncated pyramids and mainly non-ciliated with glycosylated granules in the cytoplasm.
32535395	8	65	theme	secretory	1194:1202	arg1	granules					1204:1211	fewer secretory granules	1188:1211	fewer secretory granules	1188:1211	By Days 12 and 15 post-ovulation these cells were more cuboidal and some showed fewer secretory granules.
32535395	3	66	theme	embryo	565:570	arg1	effect					552:557	the local effect	542:557	the local effect of an embryo on glycosylation in the endometrium	542:606	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	0	67	from	glycosylation	54:66	arg1	endometrium					75:85	the endometrium	71:85	the endometrium of the mare	71:97	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.
32535395	5	68	theme	truncated	824:832	arg1	pyramids					834:841	truncated pyramids	824:841	truncated pyramids	824:841	During estrus, lumenal epithelial cells were as truncated pyramids and mainly non-ciliated with glycosylated granules in the cytoplasm.
32535395	1	69	theme	Day	105:107	arg1	6.5-7					109:113	Day 6.5-7	105:113	Day 6.5-7 post-conception until its loss around Day 22	105:158	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
32535395	11	70	theme	blastocyst	1747:1756	arg1	capsule					1758:1764	the blastocyst capsule	1743:1764	the blastocyst capsule	1743:1764	Glycosylation in ciliated cells on Days 12 and 15 of pregnancy showed a striking similarity to that of the blastocyst capsule.
32535395	5	71	theme	epithelial	799:808	arg1	cells					810:814	lumenal epithelial cells	791:814	lumenal epithelial cells	791:814	During estrus, lumenal epithelial cells were as truncated pyramids and mainly non-ciliated with glycosylated granules in the cytoplasm.
32535395	11	72	from	Glycosylation	1640:1652	arg1	Days					1675:1678	Days 12 and 15	1675:1688	Days	1675:1678	Glycosylation in ciliated cells on Days 12 and 15 of pregnancy showed a striking similarity to that of the blastocyst capsule.
32535395	11	72	from	Glycosylation	1640:1652	arg1	15					1687:1688	15	1687:1688	15	1687:1688	Glycosylation in ciliated cells on Days 12 and 15 of pregnancy showed a striking similarity to that of the blastocyst capsule.
32535395	11	72	from	Glycosylation	1640:1652	arg1	cells					1666:1670	ciliated cells	1657:1670	ciliated cells	1657:1670	Glycosylation in ciliated cells on Days 12 and 15 of pregnancy showed a striking similarity to that of the blastocyst capsule.
32535395	7	73	contain	had	1050:1052	arg1	days					967:970	Five days	962:970	Five days post-ovulation	962:985	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	7	73	contain	had	1050:1052	arg2	granules					1098:1105	accumulated many highly glycosylated apical granules	1054:1105	accumulated many highly glycosylated apical granules	1054:1105	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	7	73	contain	had	1050:1052	arg1	cells					1001:1005	non-ciliated cells	988:1005	non-ciliated cells of the lumenal epithelium	988:1031	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	13	74	theme	epithelial	1976:1985	arg1	glycoproteins					1997:2009	epithelial secretory glycoproteins	1976:2009	epithelial secretory glycoproteins	1976:2009	We speculate that, as well as providing nourishment for the developing embryo, epithelial secretory glycoproteins may contribute components to the capsule, which develops only partially in embryos cultured in vitro.
32535395	8	75	dep	Days	1111:1114	arg1	post-ovulation					1126:1139	15 post-ovulation	1123:1139	15 post-ovulation	1123:1139	By Days 12 and 15 post-ovulation these cells were more cuboidal and some showed fewer secretory granules.
32535395	8	75	dep	Days	1111:1114	arg1	12					1116:1117	12	1116:1117	12	1116:1117	By Days 12 and 15 post-ovulation these cells were more cuboidal and some showed fewer secretory granules.
32535395	11	76	theme	pregnancy	1693:1701	arg1	Days					1675:1678	Days 12 and 15	1675:1688	Days	1675:1678	Glycosylation in ciliated cells on Days 12 and 15 of pregnancy showed a striking similarity to that of the blastocyst capsule.
32535395	6	77	theme	ciliated	923:930	arg1	cells					932:936	Occasional ciliated cells	912:936	Occasional ciliated cells	912:936	Occasional ciliated cells contained few granules.
32535395	4	78	theme	diestrus	690:697	arg1	Days					666:669	Days 5, 8, 12 and 15	666:685	Days 5, 8, 12 and 15 of diestrus	666:697	Endometrial biopsies were taken from mares in estrus, on Days 5, 8, 12 and 15 of diestrus, and on Days 12 and 15 of pregnancy and processed for lectin histochemistry.
32535395	3	79	from	glycosylation	575:587	arg1	endometrium					596:606	the endometrium	592:606	the endometrium	592:606	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	3	80	theme	glycan	457:462	arg1	composition					464:474	glycan composition	457:474	glycan composition	457:474	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	0	81	theme	mare	94:97	arg1	endometrium					75:85	the endometrium	71:85	the endometrium of the mare	71:97	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.
32535395	9	82	theme	apical	1369:1374	arg1	cytoplasm					1376:1384	the apical cytoplasm	1365:1384	the apical cytoplasm	1365:1384	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	5	83	gly	glycosylated	872:883	arg1	granules					885:892	glycosylated granules	872:892	glycosylated granules in the cytoplasm	872:909	During estrus, lumenal epithelial cells were as truncated pyramids and mainly non-ciliated with glycosylated granules in the cytoplasm.
32535395	10	84	theme	overall	1571:1577	arg1	reduction					1579:1587	an overall reduction	1568:1587	an overall reduction in sialic acid and several other sugar structures	1568:1637	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	12	85	theme	luminal	1826:1832	arg1	cells					1845:1849	luminal epithelial cells	1826:1849	luminal epithelial cells	1826:1849	The data strongly suggests that glycoprotein production by luminal epithelial cells is influenced by the presence of a conceptus.
32535395	0	86	theme	cycle	18:22	arg1	stage					24:28	cycle stage	18:28	cycle stage	18:28	The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.
32535395	9	87	theme	pregnancy	1255:1263	arg1	Days					1237:1240	Days 12 and 15	1237:1250	Days	1237:1240	In marked contrast, by Days 12 and 15 of pregnancy, the ciliated cells were distended, with numerous granules but non-ciliated cells had only a few in the apical cytoplasm.
32535395	5	88	theme	glycosylated	872:883	arg1	granules					885:892	glycosylated granules	872:892	glycosylated granules in the cytoplasm	872:909	During estrus, lumenal epithelial cells were as truncated pyramids and mainly non-ciliated with glycosylated granules in the cytoplasm.
32535395	3	89	gly	glycoproteins	487:499	arg1	glycoproteins					487:499	uterine glycoproteins	479:499	uterine glycoproteins destined for secretion	479:522	In this study, lectin histochemistry was used to characterise the distribution and glycan composition of uterine glycoproteins destined for secretion, and to ascertain the local effect of an embryo on glycosylation in the endometrium.
32535395	6	90	contain	contained	938:946	arg1	cells					932:936	Occasional ciliated cells	912:936	Occasional ciliated cells	912:936	Occasional ciliated cells contained few granules.
32535395	6	90	contain	contained	938:946	arg2	granules					952:959	few granules	948:959	few granules	948:959	Occasional ciliated cells contained few granules.
32535395	7	91	theme	apical	1091:1096	arg1	granules					1098:1105	accumulated many highly glycosylated apical granules	1054:1105	accumulated many highly glycosylated apical granules	1054:1105	Five days post-ovulation, non-ciliated cells of the lumenal epithelium were taller, and had accumulated many highly glycosylated apical granules.
32535395	10	92	theme	sugar	1622:1626	arg1	structures					1628:1637	several other sugar structures	1608:1637	several other sugar structures	1608:1637	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	10	93	theme	several	1608:1614	arg1	structures					1628:1637	several other sugar structures	1608:1637	several other sugar structures	1608:1637	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	10	94	theme	gland	1466:1470	arg1	epithelium					1472:1481	the luminal and superficial gland epithelium	1438:1481	the luminal and superficial gland epithelium	1438:1481	Glycosylation changed dramatically in pregnancy in the luminal and superficial gland epithelium, with fewer fucosylated termini, more N-acetyl galactosamine residues, together with an overall reduction in sialic acid and several other sugar structures.
32535395	1	95	theme	mucinous	196:203	arg1	capsule					205:211	a mucinous capsule	194:211	a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium	194:307	From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium.
33030205	6	0	theme	CH-π	1396:1399	arg1	interactions					1401:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	5	1	gly	O-glycopeptide	912:925	arg2	O-glycopeptide					912:925	an O-glycopeptide	909:925	an O-glycopeptide	909:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	3	2	from	aeruginosa	481:490	arg1	IMPa					459:462	IMPa	459:462	IMPa from Pseudomonas aeruginosa	459:490	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	3	2	from	aeruginosa	481:490	arg1	O-glycopeptidase					503:518	such an O-glycopeptidase	495:518	such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction	495:691	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	6	3	theme	aromatic	1369:1376	arg1	interactions					1401:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	5	4	from	structure	875:883	arg1	complex					896:902	complex	896:902	complex with an O-glycopeptide	896:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	7	5	theme	mucin-like	1627:1636	arg1	molecules					1638:1646	mucin-like molecules	1627:1646	mucin-like molecules	1627:1646	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	6	6	theme	ring-carbohydrate	1378:1394	arg1	interactions					1401:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	7	7	theme	glycoprotein-specific	1505:1525	arg1	peptidases					1527:1536	glycoprotein-specific peptidases	1505:1536	glycoprotein-specific peptidases	1505:1536	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	5	8	theme	N-terminal	947:956	arg1	IMPa					968:971	IMPa	968:971	IMPa	968:971	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	8	theme	N-terminal	947:956	arg1	IMPa_N_2					1005:1012	IMPa_N_2	1005:1012	IMPa_N_2	1005:1012	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	8	theme	N-terminal	947:956	arg1	domain					1040:1045	a proline recognition domain	1018:1045	a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline	1018:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	8	theme	N-terminal	947:956	arg1	domain					958:963	the N-terminal domain	943:963	the N-terminal domain	943:963	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	1	9	gly	glycosylation	103:115	arg1	proteins					120:127	proteins	120:127	proteins	120:127	The glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis.
33030205	6	10	theme	glycan	1292:1297	arg1	wraps					1299:1303	the glycan wraps	1288:1303	the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1288:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	2	11	theme	protective	312:321	arg1	effect					323:328	the protective effect	308:328	the protective effect of glycans against proteolysis	308:359	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	5	12	link	O-linked	1096:1103	arg1	glycan					1105:1110	an O-linked glycan	1093:1110	an O-linked glycan on the serine/threonine residue following the proline	1093:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	6	13	theme	classic	1361:1367	arg1	interactions					1401:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	classic aromatic ring-carbohydrate CH-π interactions	1361:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	0	14	from	domain	68:73	arg1	O-glycopeptidase					81:96	an O-glycopeptidase	78:96	an O-glycopeptidase	78:96	Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase.
33030205	7	15	from	domains	1494:1500	arg1	peptidases					1527:1536	glycoprotein-specific peptidases	1505:1536	glycoprotein-specific peptidases	1505:1536	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	3	16	dep	cleaves	525:531	arg1	contributes					648:658	contributes	648:658	contributes to the host-pathogen interaction	648:691	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	7	17	from	common	1607:1612	arg1	mucin					1617:1621	mucin	1617:1621	mucin	1617:1621	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	7	17	from	common	1607:1612	arg1	molecules					1638:1646	mucin-like molecules	1627:1646	mucin-like molecules	1627:1646	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	5	18	theme	serine/threonine	1119:1134	arg1	residue					1136:1142	the serine/threonine residue	1115:1142	the serine/threonine residue following the proline	1115:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	7	19	theme	unprecedented	1449:1461	arg1	insight					1463:1469	unprecedented insight	1449:1469	unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules	1449:1646	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	5	20	theme	crystal	867:873	arg1	structure					875:883	a crystal structure	865:883	a crystal structure of IMPa in complex with an O-glycopeptide	865:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	2	21	theme	specific	415:422	arg1	features					424:431	specific features	415:431	specific features of substrate recognition	415:456	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	2	21	theme	specific	415:422	arg1	glycans					382:388	the glycans	378:388	the glycans in their active sites	378:410	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	7	22	theme	ancillary	1484:1492	arg1	domains					1494:1500	the ancillary domains	1480:1500	the ancillary domains in glycoprotein-specific peptidases	1480:1536	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	6	23	theme	side	1270:1273	arg1	chains					1275:1280	four functionally conserved aromatic amino acid side chains	1222:1280	four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1222:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	2	24	from	glycans	382:388	arg1	sites					406:410	their active sites	393:410	their active sites	393:410	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	4	25	theme	multidomain	731:741	arg1	protein					743:749	a relatively large multidomain protein	712:749	a relatively large multidomain protein	712:749	IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown.
33030205	4	25	theme	multidomain	731:741	arg1	IMPa					694:697	IMPa	694:697	IMPa	694:697	IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown.
33030205	0	26	theme	Structural	0:9	arg1	evidence					11:18	Structural evidence	0:18	Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase.	0:97	Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase.
33030205	6	27	theme	acid	1265:1268	arg1	chains					1275:1280	four functionally conserved aromatic amino acid side chains	1222:1280	four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1222:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	3	28	theme	glycoprotein-degrading	616:637	arg1	function					639:646	this glycoprotein-degrading function	611:646	this glycoprotein-degrading function	611:646	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	4	29	theme	large	725:729	arg1	protein					743:749	a relatively large multidomain protein	712:749	a relatively large multidomain protein	712:749	IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown.
33030205	4	29	theme	large	725:729	arg1	IMPa					694:697	IMPa	694:697	IMPa	694:697	IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown.
33030205	5	30	theme	structure	875:883	arg1	determination					848:860	the determination	844:860	the determination of a crystal structure of IMPa in complex with an O-glycopeptide	844:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	31	theme	proline	1020:1026	arg1	IMPa					968:971	IMPa	968:971	IMPa	968:971	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	31	theme	proline	1020:1026	arg1	domain					958:963	the N-terminal domain	943:963	the N-terminal domain	943:963	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	31	theme	proline	1020:1026	arg1	domain					1040:1045	a proline recognition domain	1018:1045	a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline	1018:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	32	with	complex	896:902	arg1	O-glycopeptide					912:925	an O-glycopeptide	909:925	an O-glycopeptide	909:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	33	theme	IMPa	888:891	arg1	structure					875:883	a crystal structure	865:883	a crystal structure of IMPa in complex with an O-glycopeptide	865:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	2	34	theme	glycans	333:339	arg1	effect					323:328	the protective effect	308:328	the protective effect of glycans against proteolysis	308:359	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	7	35	from	molecules	1638:1646	arg1	common					1607:1612	common	1607:1612	common	1607:1612	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	1	36	theme	proteins	120:127	arg1	glycosylation					103:115	The glycosylation	99:115	The glycosylation of proteins	99:127	The glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis.
33030205	1	36	theme	proteins	120:127	arg1	modification					170:181	a stabilizing modification	156:181	a stabilizing modification	156:181	The glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis.
33030205	2	37	theme	recognition	446:456	arg1	features					424:431	specific features	415:431	specific features of substrate recognition	415:456	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	2	37	theme	recognition	446:456	arg1	glycans					382:388	the glycans	378:388	the glycans in their active sites	378:410	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	0	38	theme	glycopeptide	43:54	arg1	domain					68:73	a proline-specific glycopeptide recognition domain	24:73	a proline-specific glycopeptide recognition domain in an O-glycopeptidase	24:96	Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase.
33030205	4	39	theme	additional	763:772	arg1	domains					774:780	its additional domains	759:780	its additional domains	759:780	IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown.
33030205	5	40	theme	O-linked	1096:1103	arg1	glycan					1105:1110	an O-linked glycan	1093:1110	an O-linked glycan on the serine/threonine residue following the proline	1093:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	6	41	theme	amino	1259:1263	arg1	chains					1275:1280	four functionally conserved aromatic amino acid side chains	1222:1280	four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1222:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	2	42	theme	substrate	436:444	arg1	recognition					446:456	substrate recognition	436:456	substrate recognition	436:456	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	0	43	theme	proline-specific	26:41	arg1	domain					68:73	a proline-specific glycopeptide recognition domain	24:73	a proline-specific glycopeptide recognition domain in an O-glycopeptidase	24:96	Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase.
33030205	6	44	theme	residues	1332:1339	arg1	one					1312:1314	one	1312:1314	one	1312:1314	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	6	44	theme	residues	1332:1339	arg1	residues					1332:1339	the tyrosine residues	1319:1339	the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1319:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	6	45	theme	aromatic	1250:1257	arg1	chains					1275:1280	four functionally conserved aromatic amino acid side chains	1222:1280	four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1222:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	5	46	from	complex	896:902	arg1	determination					848:860	the determination	844:860	the determination of a crystal structure of IMPa in complex with an O-glycopeptide	844:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	47	from	glycan	1105:1110	arg1	residue					1136:1142	the serine/threonine residue	1115:1142	the serine/threonine residue following the proline	1115:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	6	48	theme	tyrosine	1323:1330	arg1	residues					1332:1339	the tyrosine residues	1319:1339	the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1319:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	6	49	from	residues	1332:1339	arg1	bowl					1348:1351	the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1344:1412	the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1344:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	6	50	theme	conserved	1240:1248	arg1	chains					1275:1280	four functionally conserved aromatic amino acid side chains	1222:1280	four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1222:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	0	51	theme	recognition	56:66	arg1	domain					68:73	a proline-specific glycopeptide recognition domain	24:73	a proline-specific glycopeptide recognition domain in an O-glycopeptidase	24:96	Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase.
33030205	5	52	from	determination	848:860	arg1	complex					896:902	complex	896:902	complex with an O-glycopeptide	896:925	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	7	53	theme	glycosylated	1578:1589	arg1	motifs					1591:1596	specific glycosylated motifs	1569:1596	specific glycosylated motifs that are common in mucin and mucin-like molecules	1569:1646	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	2	54	theme	peptidases	232:241	arg1	class					223:227	A class	221:227	A class	221:227	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	3	55	theme	peptide	537:543	arg1	bond					545:548	the peptide bond	533:548	the peptide bond immediately preceding a site of O-glycosylation	533:596	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	6	56	theme	bowl	1207:1210	arg1	center					1195:1200	the center	1191:1200	the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions	1191:1412	The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions.
33030205	5	57	theme	IMPa	968:971	arg1	IMPa					968:971	IMPa	968:971	IMPa	968:971	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	57	theme	IMPa	968:971	arg1	IMPa_N_2					1005:1012	IMPa_N_2	1005:1012	IMPa_N_2	1005:1012	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	57	theme	IMPa	968:971	arg1	domain					1040:1045	a proline recognition domain	1018:1045	a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline	1018:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	57	theme	IMPa	968:971	arg1	domain					958:963	the N-terminal domain	943:963	the N-terminal domain	943:963	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	7	58	gly	glycosylated	1578:1589	arg1	motifs					1591:1596	specific glycosylated motifs	1569:1596	specific glycosylated motifs that are common in mucin and mucin-like molecules	1569:1646	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	7	59	theme	structural	1420:1429	arg1	evidence					1431:1438	This structural evidence	1415:1438	This structural evidence	1415:1438	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	0	60	gly	glycopeptide	43:54	arg2	glycopeptide					43:54	a proline-specific glycopeptide recognition domain	24:73	a proline-specific glycopeptide recognition domain in an O-glycopeptidase	24:96	Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase.
33030205	1	61	theme	stabilizing	158:168	arg1	glycosylation					103:115	The glycosylation	99:115	The glycosylation of proteins	99:127	The glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis.
33030205	1	61	theme	stabilizing	158:168	arg1	modification					170:181	a stabilizing modification	156:181	a stabilizing modification	156:181	The glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis.
33030205	7	62	theme	specific	1569:1576	arg1	motifs					1591:1596	specific glycosylated motifs	1569:1596	specific glycosylated motifs that are common in mucin and mucin-like molecules	1569:1646	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	3	63	theme	host-pathogen	667:679	arg1	interaction					681:691	the host-pathogen interaction	663:691	the host-pathogen interaction	663:691	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	2	64	theme	active	399:404	arg1	sites					406:410	their active sites	393:410	their active sites	393:410	A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition.
33030205	7	65	from	mucin	1617:1621	arg1	common					1607:1612	common	1607:1612	common	1607:1612	This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.
33030205	3	66	theme	O-glycosylation	582:596	arg1	O-glycosylation					582:596	O-glycosylation	582:596	O-glycosylation	582:596	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	3	66	theme	O-glycosylation	582:596	arg1	site					574:577	a site	572:577	a site of O-glycosylation	572:596	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	5	67	theme	recognition	1028:1038	arg1	IMPa					968:971	IMPa	968:971	IMPa	968:971	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	67	theme	recognition	1028:1038	arg1	domain					958:963	the N-terminal domain	943:963	the N-terminal domain	943:963	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	5	67	theme	recognition	1028:1038	arg1	domain					1040:1045	a proline recognition domain	1018:1045	a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline	1018:1164	Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline.
33030205	3	68	gly	O-glycosylation	582:596	arg2	site					574:577	a site	572:577	a site of O-glycosylation	572:596	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
33030205	3	68	gly	O-glycosylation	582:596	arg2	O-glycosylation					582:596	O-glycosylation	582:596	O-glycosylation	582:596	IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction.
32445493	0	0	theme	Lectin	86:91	arg1	Targeting					93:101	Improved Lectin Targeting	77:101	Improved Lectin Targeting	77:101	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	2	1	theme	increased	493:501	arg1	affinity					503:510	increased affinity	493:510	increased affinity	493:510	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	2	2	theme	disaccharide	609:620	arg1	mimetics					622:629	mono and disaccharide mimetics	600:629	mimetics	622:629	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	3	3	theme	structures	1001:1010	arg1	panel					972:976	a panel	970:976	a panel of complex glycan core structures	970:1010	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	3	4	theme	subsequent	1124:1133	arg1	cycloaddition					1135:1147	subsequent cycloaddition	1124:1147	subsequent cycloaddition with a collection of alkynes	1124:1176	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	3	5	theme	N-glycan	913:920	arg1	mimetics					922:929	N-glycan mimetics	913:929	N-glycan mimetics	913:929	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	0	6	theme	Improved	77:84	arg1	Targeting					93:101	Improved Lectin Targeting	77:101	Improved Lectin Targeting	77:101	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	5	7	theme	lead	1471:1474	arg1	structures					1476:1485	lead structures	1471:1485	lead structures for more selective lectin targeting probes	1471:1528	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	5	7	theme	lead	1471:1474	arg1	number					1436:1441	a number	1434:1441	a number of high affinity binders	1434:1466	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	0	8	from	Scaffolds	63:71	arg1	Synthesis					14:22	Rapid On-Chip Synthesis	0:22	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.	0:102	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	5	9	theme	374	1320:1322	arg1	N-glycomimetics					1324:1338	374 N-glycomimetics	1320:1338	374 N-glycomimetics	1320:1338	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	3	10	theme	nonnatural	1103:1112	arg1	donor					1114:1118	a nonnatural donor	1101:1118	a nonnatural donor	1101:1118	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	2	11	theme	natural	537:543	arg1	binders					552:558	the natural glycan binders	533:558	the natural glycan binders	533:558	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	5	12	theme	lectin	1358:1363	arg1	WFA					1365:1367	the plant lectin WFA	1348:1367	the plant lectin WFA	1348:1367	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	2	13	theme	mono	600:603	arg1	mimetics					622:629	mono and disaccharide mimetics	600:629	mimetics	622:629	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	3	14	theme	diverse	1030:1036	arg1	glycomimetics					1038:1050	structurally diverse glycomimetics	1017:1050	structurally diverse glycomimetics	1017:1050	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	5	15	theme	N-glycomimetics	1324:1338	arg1	collection					1306:1315	the collection	1302:1315	the collection of 374 N-glycomimetics	1302:1338	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	1	16	theme	immune	356:361	arg1	therapy					363:369	the immune therapy	352:369	the immune therapy of cancer autoimmune diseases and inflammation	352:416	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	3	17	theme	glycan	989:994	arg1	structures					1001:1010	complex glycan core structures	981:1010	complex glycan core structures	981:1010	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	1	18	theme	vaccines	449:456	arg1	efficacy					437:444	the efficacy	433:444	the efficacy of vaccines	433:456	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	2	19	theme	additional	786:795	arg1	interactions					807:818	additional favorable interactions	786:818	additional favorable interactions beyond the primary binding site	786:850	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	5	20	theme	MGL	1400:1402	arg1	ECD					1404:1406	the 2 human immune lectins MGL ECD and Langerin ECD	1373:1423	ECD	1404:1406	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	5	21	theme	human	1379:1383	arg1	lectins					1392:1398	human immune lectins	1379:1398	human immune lectins	1379:1398	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	2	22	theme	array	642:646	arg1	experiments					656:666	glycan array binding experiments	635:666	glycan array binding experiments	635:666	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	2	23	theme	binding	648:654	arg1	experiments					656:666	glycan array binding experiments	635:666	glycan array binding experiments	635:666	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	5	24	theme	plant	1352:1356	arg1	WFA					1365:1367	the plant lectin WFA	1348:1367	the plant lectin WFA	1348:1367	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	1	25	located	found	163:167	arg1	cells					179:183	immune cells	172:183	immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	172:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	1	25	located	found	163:167	arg2	proteins					154:161	C-type lectin receptor (CLR) carbohydrate binding proteins	104:161	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	104:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	2	26	theme	glycan	635:640	arg1	experiments					656:666	glycan array binding experiments	635:666	glycan array binding experiments	635:666	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	3	27	theme	enzymatic	1072:1080	arg1	glycosylation					1082:1094	enzymatic glycosylation	1072:1094	enzymatic glycosylation with a nonnatural donor	1072:1118	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	3	28	theme	mimetics	922:929	arg1	screening					900:908	screening	900:908	screening	900:908	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	3	28	theme	mimetics	922:929	arg1	preparation					884:894	rapid preparation	878:894	rapid preparation	878:894	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	1	29	theme	immune	172:177	arg1	cells					179:183	immune cells	172:183	immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	172:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	0	30	theme	On-Chip	6:12	arg1	Synthesis					14:22	Rapid On-Chip Synthesis	0:22	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.	0:102	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	1	31	theme	cancer	374:379	arg1	therapy					363:369	the immune therapy	352:369	the immune therapy of cancer autoimmune diseases and inflammation	352:416	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	4	32	theme	MALDI-TOF	1225:1233	arg1	MS					1235:1236	MALDI-TOF MS	1225:1236	MALDI-TOF MS	1225:1236	All surface-based reactions were monitored by MALDI-TOF MS to assess conversion and purity of spot compositions.
32445493	3	33	theme	glycosylation	1082:1094	arg1	cycloaddition					1135:1147	subsequent cycloaddition	1124:1147	subsequent cycloaddition with a collection of alkynes	1124:1176	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	3	33	theme	glycosylation	1082:1094	arg1	combination					1057:1067	a combination	1055:1067	a combination of enzymatic glycosylation with a nonnatural donor	1055:1118	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	4	34	theme	surface-based	1183:1195	arg1	reactions					1197:1205	All surface-based reactions	1179:1205	All surface-based reactions	1179:1205	All surface-based reactions were monitored by MALDI-TOF MS to assess conversion and purity of spot compositions.
32445493	0	35	theme	Rapid	0:4	arg1	Synthesis					14:22	Rapid On-Chip Synthesis	0:22	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.	0:102	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	3	36	with	combination	1057:1067	arg1	collection					1156:1165	a collection	1154:1165	a collection of alkynes	1154:1176	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	2	37	theme	mimetics	622:629	arg1	synthesis					587:595	the synthesis	583:595	the synthesis of mono and disaccharide mimetics	583:629	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	2	38	theme	binding	689:695	arg1	selectivity					697:707	increased binding selectivity	679:707	increased binding selectivity	679:707	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	5	39	theme	selective	1496:1504	arg1	lectin					1506:1511	more selective lectin	1491:1511	more selective lectin targeting probes	1491:1528	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	4	40	theme	spot	1273:1276	arg1	compositions					1278:1289	spot compositions	1273:1289	spot compositions	1273:1289	All surface-based reactions were monitored by MALDI-TOF MS to assess conversion and purity of spot compositions.
32445493	2	41	theme	increased	679:687	arg1	selectivity					697:707	increased binding selectivity	679:707	increased binding selectivity	679:707	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	1	42	theme	C-type	104:109	arg1	CLR					128:130	CLR	128:130	CLR	128:130	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	1	42	theme	C-type	104:109	arg1	receptor					118:125	C-type lectin receptor	104:125	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	104:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	1	43	theme	important	190:198	arg1	functions					200:208	important functions	190:208	important functions in pathogen recognition as well as self and non-self-differentiation	190:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	2	44	theme	molecules	478:486	arg1	development					463:473	The development	459:473	The development of molecules with increased affinity and selectivity over the natural glycan binders	459:558	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	3	45	theme	alkynes	1170:1176	arg1	collection					1156:1165	a collection	1154:1165	a collection of alkynes	1154:1176	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	1	46	theme	autoimmune	381:390	arg1	diseases					392:399	autoimmune diseases	381:399	autoimmune diseases	381:399	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	1	47	theme	lectin	111:116	arg1	CLR					128:130	CLR	128:130	CLR	128:130	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	1	47	theme	lectin	111:116	arg1	receptor					118:125	C-type lectin receptor	104:125	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	104:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	0	48	theme	Glycomimetics	35:47	arg1	Synthesis					14:22	Rapid On-Chip Synthesis	0:22	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.	0:102	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	3	49	with	glycosylation	1082:1094	arg1	donor					1114:1118	a nonnatural donor	1101:1118	a nonnatural donor	1101:1118	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	2	50	theme	favorable	797:805	arg1	interactions					807:818	additional favorable interactions	786:818	additional favorable interactions beyond the primary binding site	786:850	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	0	51	theme	Complex	27:33	arg1	Glycomimetics					35:47	Complex Glycomimetics	27:47	Complex Glycomimetics	27:47	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	2	52	theme	glycan	545:550	arg1	binders					552:558	the natural glycan binders	533:558	the natural glycan binders	533:558	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	2	53	theme	larger	735:740	arg1	oligosaccharides					742:757	selected larger oligosaccharides	726:757	selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site	726:850	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	1	54	theme	pathogen	213:220	arg1	recognition					222:232	pathogen recognition	213:232	pathogen recognition	213:232	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	0	55	theme	N-Glycan	54:61	arg1	Scaffolds					63:71	N-Glycan Scaffolds	54:71	N-Glycan Scaffolds for Improved Lectin Targeting	54:101	Rapid On-Chip Synthesis of Complex Glycomimetics from N-Glycan Scaffolds for Improved Lectin Targeting.
32445493	1	56	dep	cancer	374:379	arg1	diseases					392:399	autoimmune diseases	381:399	autoimmune diseases	381:399	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	1	57	with	cells	179:183	arg1	functions					200:208	important functions	190:208	important functions in pathogen recognition as well as self and non-self-differentiation	190:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	1	58	theme	inflammation	405:416	arg1	therapy					363:369	the immune therapy	352:369	the immune therapy of cancer autoimmune diseases and inflammation	352:416	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	2	59	theme	selected	726:733	arg1	oligosaccharides					742:757	selected larger oligosaccharides	726:757	selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site	726:850	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	1	60	theme	receptor	118:125	arg1	proteins					154:161	C-type lectin receptor (CLR) carbohydrate binding proteins	104:161	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	104:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	3	61	from	platform	861:868	arg1	microarrays					934:944	microarrays	934:944	microarrays	934:944	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	1	62	theme	drug	321:324	arg1	developers					326:335	drug developers	321:335	drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation	321:416	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	3	63	theme	rapid	878:882	arg1	preparation					884:894	rapid preparation	878:894	rapid preparation	878:894	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	1	64	theme	developers	326:335	arg1	focus					312:316	the focus	308:316	the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation	308:416	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	5	65	theme	binders	1460:1466	arg1	structures					1476:1485	lead structures	1471:1485	lead structures for more selective lectin targeting probes	1471:1528	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	5	65	theme	binders	1460:1466	arg1	number					1436:1441	a number	1434:1441	a number of high affinity binders	1434:1466	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	5	66	theme	affinity	1451:1458	arg1	binders					1460:1466	high affinity binders	1446:1466	high affinity binders	1446:1466	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	1	67	from	functions	200:208	arg1	recognition					222:232	pathogen recognition	213:232	pathogen recognition	213:232	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	3	68	with	cycloaddition	1135:1147	arg1	collection					1156:1165	a collection	1154:1165	a collection of alkynes	1154:1176	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	3	69	theme	core	996:999	arg1	structures					1001:1010	complex glycan core structures	981:1010	complex glycan core structures	981:1010	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	5	70	theme	high	1446:1449	arg1	binders					1460:1466	high affinity binders	1446:1466	high affinity binders	1446:1466	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	3	71	theme	complex	981:987	arg1	structures					1001:1010	complex glycan core structures	981:1010	complex glycan core structures	981:1010	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	2	72	theme	binding	839:845	arg1	site					847:850	the primary binding site	827:850	the primary binding site	827:850	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	5	73	theme	lectins	1392:1398	arg1	ECD					1404:1406	the 2 human immune lectins MGL ECD and Langerin ECD	1373:1423	ECD	1404:1406	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	5	74	theme	Langerin	1412:1419	arg1	ECD					1421:1423	the 2 human immune lectins MGL ECD and Langerin ECD	1373:1423	ECD	1421:1423	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	1	75	theme	carbohydrate	133:144	arg1	proteins					154:161	C-type lectin receptor (CLR) carbohydrate binding proteins	104:161	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	104:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32445493	2	76	theme	primary	831:837	arg1	site					847:850	the primary binding site	827:850	the primary binding site	827:850	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	4	77	theme	compositions	1278:1289	arg1	purity					1263:1268	purity	1263:1268	purity	1263:1268	All surface-based reactions were monitored by MALDI-TOF MS to assess conversion and purity of spot compositions.
32445493	4	77	theme	compositions	1278:1289	arg1	conversion					1248:1257	conversion	1248:1257	conversion	1248:1257	All surface-based reactions were monitored by MALDI-TOF MS to assess conversion and purity of spot compositions.
32445493	5	78	theme	immune	1385:1390	arg1	lectins					1392:1398	human immune lectins	1379:1398	human immune lectins	1379:1398	Screening the collection of 374 N-glycomimetics against the plant lectin WFA and the 2 human immune lectins MGL ECD and Langerin ECD produced a number of high affinity binders as lead structures for more selective lectin targeting probes.
32445493	3	79	dep	preparation	884:894	arg1	the					874:876	the	874:876	the	874:876	Here, a platform for the rapid preparation and screening of N-glycan mimetics on microarrays is presented that turns a panel of complex glycan core structures into structurally diverse glycomimetics by a combination of enzymatic glycosylation with a nonnatural donor and subsequent cycloaddition with a collection of alkynes.
32445493	2	80	with	molecules	478:486	arg1	affinity					503:510	increased affinity	493:510	increased affinity	493:510	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	2	80	with	molecules	478:486	arg1	selectivity					516:526	selectivity	516:526	selectivity over the natural glycan binders	516:558	The development of molecules with increased affinity and selectivity over the natural glycan binders has largely focused on the synthesis of mono and disaccharide mimetics but glycan array binding experiments have shown increased binding selectivity and affinity for selected larger oligosaccharides that are able to engage in additional favorable interactions beyond the primary binding site.
32445493	1	81	theme	binding	146:152	arg1	proteins					154:161	C-type lectin receptor (CLR) carbohydrate binding proteins	104:161	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation	104:277	C-type lectin receptor (CLR) carbohydrate binding proteins found on immune cells with important functions in pathogen recognition as well as self and non-self-differentiation are increasingly moving into the focus of drug developers as targets for the immune therapy of cancer autoimmune diseases and inflammation and to improve the efficacy of vaccines.
32039451	0	0	contain	contain	60:66	arg1	N-glycans					4:12	The N-glycans	0:12	The N-glycans of Chlorella sorokiniana and a related strain	0:58	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	0	0	contain	contain	60:66	arg2	arabinose					68:76	arabinose	68:76	arabinose	68:76	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	1	1	theme	microalgae	154:163	arg1	Chlorella					173:181	Chlorella	173:181	Chlorella	173:181	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	1	1	theme	microalgae	154:163	arg1	applications					138:149	The many emerging applications	120:149	The many emerging applications of microalgae such as Chlorella	120:181	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	4	2	theme	type	643:646	arg1	strains					667:673	type culture collection strains	643:673	type culture collection strains of C. sorokiniana	643:691	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	4	3	theme	mass	564:567	arg1	spectrometry					569:580	mass spectrometry	564:580	mass spectrometry	564:580	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	7	4	theme	considerable	1015:1026	arg1	homology					1028:1035	considerable homology	1015:1035	considerable homology in their ITS1-5.8S-ITS2 rDNA sequences	1015:1074	Despite these differences, the two algae lines exhibited considerable homology in their ITS1-5.8S-ITS2 rDNA sequences.
32039451	2	5	theme	O-methylated	359:370	arg1	N-glycans					388:396	highly O-methylated oligomannosidic N-glycans	352:396	highly O-methylated oligomannosidic N-glycans	352:396	Chlorella vulgaris has recently been shown to equip its proteins with highly O-methylated oligomannosidic N-glycans.
32039451	8	6	theme	unicellular	1228:1238	arg1	organism					1240:1247	a unicellular organism	1226:1247	a unicellular organism	1226:1247	These drastic differences of N-glycan structures between species belonging to the very same genus provoke questions as to the biological function on a unicellular organism.
32039451	7	7	theme	algae	993:997	arg1	lines					999:1003	the two algae lines	985:1003	the two algae lines	985:1003	Despite these differences, the two algae lines exhibited considerable homology in their ITS1-5.8S-ITS2 rDNA sequences.
32039451	8	8	theme	structures	1115:1124	arg1	differences					1091:1101	These drastic differences	1077:1101	These drastic differences of N-glycan structures between species belonging to the very same genus	1077:1173	These drastic differences of N-glycan structures between species belonging to the very same genus provoke questions as to the biological function on a unicellular organism.
32039451	4	9	theme	collection	656:665	arg1	strains					667:673	type culture collection strains	643:673	type culture collection strains of C. sorokiniana	643:691	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	6	10	theme	plants	950:955	arg1	N-glycans					932:940	N-glycans	932:940	N-glycans of land plants	932:955	Apart from this only commonality, the structures differed fundamentally from each other and from that of N-glycans of land plants.
32039451	3	11	dep	ill	536:538	arg1	defined					540:546	defined	540:546	is taxonomically ill defined	519:546	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	2	12	theme	oligomannosidic	372:386	arg1	N-glycans					388:396	highly O-methylated oligomannosidic N-glycans	352:396	highly O-methylated oligomannosidic N-glycans	352:396	Chlorella vulgaris has recently been shown to equip its proteins with highly O-methylated oligomannosidic N-glycans.
32039451	4	13	theme	culture	648:654	arg1	strains					667:673	type culture collection strains	643:673	type culture collection strains of C. sorokiniana	643:691	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	6	14	theme	land	945:948	arg1	plants					950:955	land plants	945:955	land plants	945:955	Apart from this only commonality, the structures differed fundamentally from each other and from that of N-glycans of land plants.
32039451	3	15	theme	Chlorella	474:482	arg1	pyrenoidosa-even					484:499	Chlorella pyrenoidosa-even	474:499	Chlorella pyrenoidosa-even	474:499	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	0	16	theme	different	98:106	arg1	structures					108:117	strikingly different structures	87:117	strikingly different structures	87:117	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	2	17	theme	Chlorella	282:290	arg1	vulgaris					292:299	Chlorella vulgaris	282:299	Chlorella vulgaris	282:299	Chlorella vulgaris has recently been shown to equip its proteins with highly O-methylated oligomannosidic N-glycans.
32039451	4	18	theme	product	713:719	arg1	N-glycans					630:638	the N-glycans	626:638	the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa	626:742	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	8	19	theme	N-glycan	1106:1113	arg1	structures					1115:1124	N-glycan structures	1106:1124	N-glycan structures	1106:1124	These drastic differences of N-glycan structures between species belonging to the very same genus provoke questions as to the biological function on a unicellular organism.
32039451	6	20	theme	only	843:846	arg1	commonality					848:858	this only commonality	838:858	this only commonality	838:858	Apart from this only commonality, the structures differed fundamentally from each other and from that of N-glycans of land plants.
32039451	3	21	theme	occurring	420:428	arg1	species					430:436	Two other frequently occurring species	399:436	Two other frequently occurring species names	399:442	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	8	22	theme	drastic	1083:1089	arg1	differences					1091:1101	These drastic differences	1077:1101	These drastic differences of N-glycan structures between species belonging to the very same genus	1077:1173	These drastic differences of N-glycan structures between species belonging to the very same genus provoke questions as to the biological function on a unicellular organism.
32039451	0	23	theme	Chlorella	17:25	arg1	sorokiniana					27:37	Chlorella sorokiniana	17:37	Chlorella sorokiniana	17:37	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	4	24	theme	resonance	603:611	arg1	spectroscopy					613:624	nuclear magnetic resonance spectroscopy	586:624	nuclear magnetic resonance spectroscopy	586:624	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	3	25	theme	other	403:407	arg1	species					430:436	Two other frequently occurring species	399:436	Two other frequently occurring species names	399:442	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	7	26	from	homology	1028:1035	arg1	sequences					1066:1074	their ITS1-5.8S-ITS2 rDNA sequences	1040:1074	their ITS1-5.8S-ITS2 rDNA sequences	1040:1074	Despite these differences, the two algae lines exhibited considerable homology in their ITS1-5.8S-ITS2 rDNA sequences.
32039451	8	27	from	function	1214:1221	arg1	organism					1240:1247	a unicellular organism	1226:1247	a unicellular organism	1226:1247	These drastic differences of N-glycan structures between species belonging to the very same genus provoke questions as to the biological function on a unicellular organism.
32039451	4	28	theme	commercial	702:711	arg1	product					713:719	a commercial product	700:719	a commercial product labeled C. pyrenoidosa	700:742	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	0	29	theme	sorokiniana	27:37	arg1	N-glycans					4:12	The N-glycans	0:12	The N-glycans of Chlorella sorokiniana and a related strain	0:58	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	5	30	contain	contained	758:766	arg1	samples					750:756	Both samples	745:756	Both samples	745:756	Both samples contained arabinose, which has hitherto not been found in N-glycans.
32039451	5	30	contain	contained	758:766	arg2	arabinose					768:776	arabinose	768:776	arabinose	768:776	Both samples contained arabinose, which has hitherto not been found in N-glycans.
32039451	3	31	theme	Chlorella	448:456	arg1	names					438:442	Two other frequently occurring species names	399:442	Two other frequently occurring species names	399:442	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	3	31	theme	Chlorella	448:456	arg1	sorokiniana					458:468	Chlorella sorokiniana	448:468	Chlorella sorokiniana	448:468	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	4	32	theme	sorokiniana	681:691	arg1	strains					667:673	type culture collection strains	643:673	type culture collection strains of C. sorokiniana	643:691	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	3	33	theme	species	430:436	arg1	names					438:442	Two other frequently occurring species names	399:442	Two other frequently occurring species names	399:442	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	3	33	theme	species	430:436	arg1	sorokiniana					458:468	Chlorella sorokiniana	448:468	Chlorella sorokiniana	448:468	Two other frequently occurring species names are Chlorella sorokiniana and Chlorella pyrenoidosa-even though the latter is taxonomically ill defined.
32039451	0	34	theme	strain	53:58	arg1	N-glycans					4:12	The N-glycans	0:12	The N-glycans of Chlorella sorokiniana and a related strain	0:58	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	8	35	theme	same	1164:1167	arg1	genus					1169:1173	the very same genus	1155:1173	the very same genus	1155:1173	These drastic differences of N-glycan structures between species belonging to the very same genus provoke questions as to the biological function on a unicellular organism.
32039451	4	36	theme	magnetic	594:601	arg1	resonance					603:611	nuclear magnetic resonance	586:611	nuclear magnetic resonance spectroscopy	586:624	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	0	37	contain	have	82:85	arg2	structures					108:117	strikingly different structures	87:117	strikingly different structures	87:117	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	0	37	contain	have	82:85	arg1	N-glycans					4:12	The N-glycans	0:12	The N-glycans of Chlorella sorokiniana and a related strain	0:58	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	4	38	theme	nuclear	586:592	arg1	resonance					603:611	nuclear magnetic resonance	586:611	nuclear magnetic resonance spectroscopy	586:624	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	1	39	theme	many	124:127	arg1	Chlorella					173:181	Chlorella	173:181	Chlorella	173:181	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	1	39	theme	many	124:127	arg1	applications					138:149	The many emerging applications	120:149	The many emerging applications of microalgae such as Chlorella	120:181	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	7	40	theme	ITS1-5.8S-ITS2	1046:1059	arg1	sequences					1066:1074	their ITS1-5.8S-ITS2 rDNA sequences	1040:1074	their ITS1-5.8S-ITS2 rDNA sequences	1040:1074	Despite these differences, the two algae lines exhibited considerable homology in their ITS1-5.8S-ITS2 rDNA sequences.
32039451	1	41	theme	emerging	129:136	arg1	Chlorella					173:181	Chlorella	173:181	Chlorella	173:181	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	1	41	theme	emerging	129:136	arg1	applications					138:149	The many emerging applications	120:149	The many emerging applications of microalgae such as Chlorella	120:181	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	4	42	theme	strains	667:673	arg1	N-glycans					630:638	the N-glycans	626:638	the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa	626:742	We analyzed by mass spectrometry and nuclear magnetic resonance spectroscopy the N-glycans of type culture collection strains of C. sorokiniana and of a commercial product labeled C. pyrenoidosa.
32039451	8	43	theme	biological	1203:1212	arg1	function					1214:1221	the biological function	1199:1221	the biological function on a unicellular organism	1199:1247	These drastic differences of N-glycan structures between species belonging to the very same genus provoke questions as to the biological function on a unicellular organism.
32039451	7	44	theme	rDNA	1061:1064	arg1	sequences					1066:1074	their ITS1-5.8S-ITS2 rDNA sequences	1040:1074	their ITS1-5.8S-ITS2 rDNA sequences	1040:1074	Despite these differences, the two algae lines exhibited considerable homology in their ITS1-5.8S-ITS2 rDNA sequences.
32039451	1	45	theme	protein	235:241	arg1	modifications					243:255	protein modifications	235:255	protein modifications such as N-glycosylation	235:279	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	1	45	theme	protein	235:241	arg1	N-glycosylation					265:279	N-glycosylation	265:279	N-glycosylation	265:279	The many emerging applications of microalgae such as Chlorella also instigate interest in their ability to conduct protein modifications such as N-glycosylation.
32039451	0	46	theme	related	45:51	arg1	strain					53:58	a related strain	43:58	a related strain	43:58	The N-glycans of Chlorella sorokiniana and a related strain contain arabinose but have strikingly different structures.
32039451	5	47	located	found	807:811	arg1	N-glycans					816:824	N-glycans	816:824	N-glycans	816:824	Both samples contained arabinose, which has hitherto not been found in N-glycans.
32039451	5	47	located	found	807:811	arg2	arabinose					768:776	arabinose	768:776	arabinose	768:776	Both samples contained arabinose, which has hitherto not been found in N-glycans.
32030495	0	0	theme	stem	98:101	arg1	cells					103:107	MCF-7/ADR cancer stem cells	81:107	MCF-7/ADR cancer stem cells	81:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	2	1	theme	linkages	647:654	arg1	combination					577:587	the combination	573:587	the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions)	573:687	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	2	theme	unique	596:601	arg1	backbones					611:619	301 unique peptide backbones	592:619	301 unique peptide backbones	592:619	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	2	theme	unique	596:601	arg1	compositions					675:686	52 monosaccharide compositions	657:686	52 monosaccharide compositions	657:686	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	3	theme	N-glycosylation	217:231	arg1	characterization					159:174	Isotopic-labeling quantitative N-glycoproteomics characterization	110:174	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	110:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	4	4	theme	≥ 1.5-fold	1135:1144	arg1	change					1146:1151	≥ 1.5-fold change	1135:1151	≥ 1.5-fold change	1135:1151	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	0	5	theme	cancer	91:96	arg1	cells					103:107	MCF-7/ADR cancer stem cells	81:107	MCF-7/ADR cancer stem cells	81:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	1	6	theme	isotopic	396:403	arg1	labeling					413:420	isotopic diethyl labeling	396:420	isotopic diethyl labeling	396:420	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	7	theme	N-glycan	638:645	arg1	linkages					647:654	169 putative N-glycan linkages	625:654	169 putative N-glycan linkages	625:654	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	8	from	N-glycosylation	217:231	arg1	CSCs					265:268	CSCs	265:268	CSCs	265:268	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	8	from	N-glycosylation	217:231	arg1	cells					258:262	MCF-7/ADR cancer stem cells	236:262	MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	236:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	3	9	theme	intact	933:938	arg1	IDs					955:957	546 intact N-glycopeptide IDs	929:957	546 intact N-glycopeptide IDs	929:957	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	4	10	theme	relative	1274:1281	arg1	CSCs					1269:1272	MCF-7/ADR CSCs	1259:1272	MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively	1259:1365	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	1	11	theme	diethyl	405:411	arg1	labeling					413:420	isotopic diethyl labeling	396:420	isotopic diethyl labeling	396:420	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	12	theme	putative	629:636	arg1	linkages					647:654	169 putative N-glycan linkages	625:654	169 putative N-glycan linkages	625:654	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	13	gly	N-glycopeptides	552:566	arg2	N-glycopeptides					552:566	1,336 intact N-glycopeptides	539:566	1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions)	539:687	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	13	gly	N-glycopeptides	552:566	arg1	combination					577:587	the combination	573:587	the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions)	573:687	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	14	theme	ion	893:895	arg1	pairs					897:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	0	15	theme	cells	103:107	arg1	markers					70:76	cell-surface N-glycoprotein markers	42:76	cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells	42:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	3	16	gly	N-glycopeptide	940:953	arg2	N-glycopeptide					940:953	546 intact N-glycopeptide IDs	929:957	546 intact N-glycopeptide IDs	929:957	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	2	17	dep	289	769:771	arg1	confirmed					830:838	confirmed	830:838	were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs	825:901	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	5	18	dep	abstract	1378:1385	arg1	Graphical					1368:1376	Graphical	1368:1376	Graphical	1368:1376	Graphical abstract.
32030495	2	19	theme	intact	545:550	arg1	N-glycopeptides					552:566	1,336 intact N-glycopeptides	539:566	1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions)	539:687	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	3	20	theme	monosaccharide	1085:1098	arg1	compositions					1100:1111	the monosaccharide compositions	1081:1111	the monosaccharide compositions	1081:1111	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	3	21	theme	N-glycan	908:915	arg1	moieties					917:924	The N-glycan moieties	904:924	The N-glycan moieties in 546 intact N-glycopeptide IDs	904:957	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	1	22	theme	MCF-7/ADR	236:244	arg1	CSCs					265:268	CSCs	265:268	CSCs	265:268	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	22	theme	MCF-7/ADR	236:244	arg1	cells					258:262	MCF-7/ADR cancer stem cells	236:262	MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	236:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	23	theme	spectrum-level	494:507	arg1	rate					525:528	a spectrum-level false discovery rate	492:528	a spectrum-level false discovery rate of ≤ 1%	492:536	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	24	theme	RPLC-MS/MS	423:432	arg1	analysis					434:441	RPLC-MS/MS analysis	423:441	RPLC-MS/MS analysis of the 1:1 mixture	423:460	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	25	theme	monosaccharide	660:673	arg1	backbones					611:619	301 unique peptide backbones	592:619	301 unique peptide backbones	592:619	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	25	theme	monosaccharide	660:673	arg1	compositions					675:686	52 monosaccharide compositions	657:686	52 monosaccharide compositions	657:686	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	26	gly	N-glycoproteins	731:745	arg1	289					769:771	289	769:771	289	769:771	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	26	gly	N-glycoproteins	731:745	arg1	N-glycoproteins					731:745	the corresponding intact N-glycoproteins	706:745	the corresponding intact N-glycoproteins	706:745	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	27	theme	cancer	246:251	arg1	CSCs					265:268	CSCs	265:268	CSCs	265:268	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	27	theme	cancer	246:251	arg1	cells					258:262	MCF-7/ADR cancer stem cells	236:262	MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	236:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	0	28	theme	quantitative	2:13	arg1	study					33:37	A quantitative N-glycoproteomics study	0:37	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells	0:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	2	29	theme	intact	724:729	arg1	289					769:771	289	769:771	289	769:771	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	29	theme	intact	724:729	arg1	N-glycoproteins					731:745	the corresponding intact N-glycoproteins	706:745	the corresponding intact N-glycoproteins	706:745	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	3	30	theme	N-glycopeptide	940:953	arg1	IDs					955:957	546 intact N-glycopeptide IDs	929:957	546 intact N-glycopeptide IDs	929:957	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	1	31	theme	stem	253:256	arg1	CSCs					265:268	CSCs	265:268	CSCs	265:268	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	31	theme	stem	253:256	arg1	cells					258:262	MCF-7/ADR cancer stem cells	236:262	MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	236:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	32	gly	N-glycosites	812:823	arg2	N-glycosites					812:823	176 N-glycosites	808:823	176 N-glycosites	808:823	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	33	theme	intact	322:327	arg1	level					344:348	the intact N-glycopeptide level	318:348	the intact N-glycopeptide level	318:348	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	34	theme	corresponding	710:722	arg1	289					769:771	289	769:771	289	769:771	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	34	theme	corresponding	710:722	arg1	N-glycoproteins					731:745	the corresponding intact N-glycoproteins	706:745	the corresponding intact N-glycoproteins	706:745	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	3	35	from	moieties	917:924	arg1	IDs					955:957	546 intact N-glycopeptide IDs	929:957	546 intact N-glycopeptide IDs	929:957	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	3	36	theme	fragment	1015:1022	arg1	ions					1024:1027	more than one structure-diagnostic fragment ions	980:1027	more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions	980:1111	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	1	37	theme	N-glycopeptide	329:342	arg1	level					344:348	the intact N-glycopeptide level	318:348	the intact N-glycopeptide level	318:348	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	38	from	characterization	159:174	arg1	CSCs					265:268	CSCs	265:268	CSCs	265:268	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	38	from	characterization	159:174	arg1	cells					258:262	MCF-7/ADR cancer stem cells	236:262	MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	236:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	39	theme	Isotopic-labeling	110:126	arg1	characterization					159:174	Isotopic-labeling quantitative N-glycoproteomics characterization	110:174	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	110:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	4	40	theme	cell-surface	1176:1187	arg1	DEGPs					1238:1242	DEGPs	1238:1242	DEGPs	1238:1242	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	40	theme	cell-surface	1176:1187	arg1	N-glycopeptides					1221:1235	72 cell-surface differentially expressed intact N-glycopeptides	1173:1235	72 cell-surface differentially expressed intact N-glycopeptides (DEGPs)	1173:1243	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	0	41	theme	N-glycoproteomics	15:31	arg1	study					33:37	A quantitative N-glycoproteomics study	0:37	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells	0:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	4	42	theme	value	1159:1163	arg1	criteria					1123:1130	the criteria	1119:1130	the criteria of ≥ 1.5-fold change and p value < 0.05	1119:1170	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	1	43	theme	quantitative	128:139	arg1	characterization					159:174	Isotopic-labeling quantitative N-glycoproteomics characterization	110:174	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	110:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	44	theme	false	509:513	arg1	rate					525:528	a spectrum-level false discovery rate	492:528	a spectrum-level false discovery rate of ≤ 1%	492:536	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	0	45	theme	cell-surface	42:53	arg1	markers					70:76	cell-surface N-glycoprotein markers	42:76	cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells	42:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	4	46	theme	p	1157:1157	arg1	value					1159:1163	p value < 0.05	1157:1170	p value < 0.05	1157:1170	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	3	47	theme	structure-diagnostic	994:1013	arg1	ions					1024:1027	more than one structure-diagnostic fragment ions	980:1027	more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions	980:1111	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	2	48	theme	discovery	515:523	arg1	rate					525:528	a spectrum-level false discovery rate	492:528	a spectrum-level false discovery rate of ≤ 1%	492:536	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	49	theme	trypsin	355:361	arg1	digestion					363:371	trypsin digestion	355:371	trypsin digestion	355:371	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	50	theme	1:1	450:452	arg1	mixture					454:460	the 1:1 mixture	446:460	the 1:1 mixture	446:460	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	51	gly	N-glycopeptide	329:342	arg2	N-glycopeptide					329:342	the intact N-glycopeptide level	318:348	the intact N-glycopeptide level	318:348	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	52	theme	relative	271:278	arg1	CSCs					265:268	CSCs	265:268	CSCs	265:268	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	52	theme	relative	271:278	arg1	cells					258:262	MCF-7/ADR cancer stem cells	236:262	MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	236:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	0	53	theme	markers	70:76	arg1	study					33:37	A quantitative N-glycoproteomics study	0:37	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells	0:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	1	54	theme	mixture	454:460	arg1	digestion					363:371	trypsin digestion	355:371	trypsin digestion	355:371	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	54	theme	mixture	454:460	arg1	search					479:484	GPSeeker DB search	467:484	GPSeeker DB search	467:484	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	54	theme	mixture	454:460	arg1	enrichment					384:393	ZIC-HILIC enrichment	374:393	ZIC-HILIC enrichment	374:393	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	54	theme	mixture	454:460	arg1	labeling					413:420	isotopic diethyl labeling	396:420	isotopic diethyl labeling	396:420	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	54	theme	mixture	454:460	arg1	analysis					434:441	RPLC-MS/MS analysis	423:441	RPLC-MS/MS analysis of the 1:1 mixture	423:460	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	4	55	theme	intact	1214:1219	arg1	DEGPs					1238:1242	DEGPs	1238:1242	DEGPs	1238:1242	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	55	theme	intact	1214:1219	arg1	N-glycopeptides					1221:1235	72 cell-surface differentially expressed intact N-glycopeptides	1173:1235	72 cell-surface differentially expressed intact N-glycopeptides (DEGPs)	1173:1243	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	56	theme	expressed	1204:1212	arg1	DEGPs					1238:1242	DEGPs	1238:1242	DEGPs	1238:1242	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	56	theme	expressed	1204:1212	arg1	N-glycopeptides					1221:1235	72 cell-surface differentially expressed intact N-glycopeptides	1173:1235	72 cell-surface differentially expressed intact N-glycopeptides (DEGPs)	1173:1243	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	1	57	theme	N-glycoproteomics	141:157	arg1	characterization					159:174	Isotopic-labeling quantitative N-glycoproteomics characterization	110:174	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	110:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	0	58	theme	N-glycoprotein	55:68	arg1	markers					70:76	cell-surface N-glycoprotein markers	42:76	cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells	42:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	2	59	gly	N-glycosites	751:762	arg2	N-glycosites					751:762	N-glycosites	751:762	N-glycosites	751:762	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	60	theme	backbones	611:619	arg1	combination					577:587	the combination	573:587	the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions)	573:687	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	4	61	theme	MCF-7/ADR	1286:1294	arg1	cells					1296:1300	MCF-7/ADR cells	1286:1300	MCF-7/ADR cells	1286:1300	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	2	62	theme	fragment	884:891	arg1	pairs					897:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	63	theme	ZIC-HILIC	374:382	arg1	enrichment					384:393	ZIC-HILIC enrichment	374:393	ZIC-HILIC enrichment	374:393	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	64	theme	peptide	603:609	arg1	backbones					611:619	301 unique peptide backbones	592:619	301 unique peptide backbones	592:619	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	64	theme	peptide	603:609	arg1	compositions					675:686	52 monosaccharide compositions	657:686	52 monosaccharide compositions	657:686	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	3	65	theme	multiple	1035:1042	arg1	structures					1052:1061	multiple linkage structures	1035:1061	multiple linkage structures	1035:1061	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	2	66	theme	b/y	880:882	arg1	pairs					897:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	67	from	combination	577:587	arg1	N-glycopeptides					552:566	1,336 intact N-glycopeptides	539:566	1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions)	539:687	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	68	gly	N-glycosylation	217:231	arg1	CSCs					265:268	CSCs	265:268	CSCs	265:268	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	68	gly	N-glycosylation	217:231	arg1	cells					258:262	MCF-7/ADR cancer stem cells	236:262	MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	236:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	1	69	theme	GPSeeker	467:474	arg1	search					479:484	GPSeeker DB search	467:484	GPSeeker DB search	467:484	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	3	70	theme	linkage	1044:1050	arg1	structures					1052:1061	multiple linkage structures	1035:1061	multiple linkage structures	1035:1061	The N-glycan moieties in 546 intact N-glycopeptide IDs were identified with more than one structure-diagnostic fragment ions where multiple linkage structures exist for each of the monosaccharide compositions.
32030495	1	71	theme	cell-surface	179:190	arg1	N-glycosylation					217:231	cell-surface differentially expressed N-glycosylation	179:231	cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	179:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	72	theme	site-determining	863:878	arg1	pairs					897:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	1	73	theme	MCF-7/ADR	283:291	arg1	cells					293:297	MCF-7/ADR cells	283:297	MCF-7/ADR cells	283:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	0	74	theme	MCF-7/ADR	81:89	arg1	cells					103:107	MCF-7/ADR cancer stem cells	81:107	MCF-7/ADR cancer stem cells	81:107	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	1	75	theme	DB	476:477	arg1	search					479:484	GPSeeker DB search	467:484	GPSeeker DB search	467:484	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	0	76	gly	N-glycoprotein	55:68	arg1	N-glycoprotein					55:68	N-glycoprotein	55:68	N-glycoprotein	55:68	A quantitative N-glycoproteomics study of cell-surface N-glycoprotein markers of MCF-7/ADR cancer stem cells.
32030495	1	77	from	cells	258:262	arg1	characterization					159:174	Isotopic-labeling quantitative N-glycoproteomics characterization	110:174	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	110:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	2	78	theme	GlcNAc-containing	845:861	arg1	pairs					897:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	GlcNAc-containing site-determining b/y fragment ion pairs	845:901	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	2	79	theme	%	536:536	arg1	rate					525:528	a spectrum-level false discovery rate	492:528	a spectrum-level false discovery rate of ≤ 1%	492:536	With a spectrum-level false discovery rate of ≤ 1%, 1,336 intact N-glycopeptides from the combination of 301 unique peptide backbones and 169 putative N-glycan linkages (52 monosaccharide compositions) were identified; the corresponding intact N-glycoproteins and N-glycosites were 289 and 305, respectively, among which 176 N-glycosites were confirmed with GlcNAc-containing site-determining b/y fragment ion pairs.
32030495	4	80	gly	N-glycopeptides	1221:1235	arg2	DEGPs					1238:1242	DEGPs	1238:1242	DEGPs	1238:1242	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	80	gly	N-glycopeptides	1221:1235	arg2	N-glycopeptides					1221:1235	72 cell-surface differentially expressed intact N-glycopeptides	1173:1235	72 cell-surface differentially expressed intact N-glycopeptides (DEGPs)	1173:1243	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	81	theme	MCF-7/ADR	1259:1267	arg1	CSCs					1269:1272	MCF-7/ADR CSCs	1259:1272	MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively	1259:1365	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	1	82	theme	expressed	207:215	arg1	N-glycosylation					217:231	cell-surface differentially expressed N-glycosylation	179:231	cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells	179:297	Isotopic-labeling quantitative N-glycoproteomics characterization of cell-surface differentially expressed N-glycosylation in MCF-7/ADR cancer stem cells (CSCs) relative to MCF-7/ADR cells was carried out at the intact N-glycopeptide level with trypsin digestion, ZIC-HILIC enrichment, isotopic diethyl labeling, RPLC-MS/MS analysis of the 1:1 mixture, and GPSeeker DB search.
32030495	4	83	theme	change	1146:1151	arg1	criteria					1123:1130	the criteria	1119:1130	the criteria of ≥ 1.5-fold change and p value < 0.05	1119:1170	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	84	located	found	1250:1254	arg2	DEGPs					1238:1242	DEGPs	1238:1242	DEGPs	1238:1242	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	84	located	found	1250:1254	arg2	N-glycopeptides					1221:1235	72 cell-surface differentially expressed intact N-glycopeptides	1173:1235	72 cell-surface differentially expressed intact N-glycopeptides (DEGPs)	1173:1243	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32030495	4	84	located	found	1250:1254	arg1	CSCs					1269:1272	MCF-7/ADR CSCs	1259:1272	MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively	1259:1365	With the criteria of ≥ 1.5-fold change and p value < 0.05, 72 cell-surface differentially expressed intact N-glycopeptides (DEGPs) were found in MCF-7/ADR CSCs relative to MCF-7/ADR cells, where 8 and 64 were downregulated and upregulated, respectively.
32304323	9	0	theme	acceptor	1766:1773	arg1	group					1782:1786	the Thr acceptor methyl group	1758:1786	the Thr acceptor methyl group binding to the active site pocket	1758:1820	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	8	1	theme	sequence	1494:1501	arg1	substrates					1503:1512	fixed sequence substrates	1488:1512	fixed sequence substrates of different relative activities	1488:1545	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	3	2	gly	glycosylation	433:445	arg2	glycosylation					433:445	glycosylation	433:445	glycosylation	433:445	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	3	2	gly	glycosylation	433:445	arg2	sites					424:428	their sites	418:428	their sites of glycosylation	418:445	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	5	3	theme	Thr	858:860	arg1	glycosylation					870:882	Thr vs. Ser glycosylation	858:882	glycosylation	870:882	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	3	4	theme	substrate	516:524	arg1	glycosylation					535:547	prior substrate O-GalNAc glycosylation	510:547	prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor	510:624	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	1	5	theme	Thr	258:260	arg1	residues					262:269	Ser and Thr residues	250:269	Ser and Thr residues of target substrates	250:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	5	theme	Thr	258:260	arg1	substrates					281:290	target substrates	274:290	target substrates	274:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	6	6	theme	rate	1062:1065	arg1	differences					1041:1051	the rate differences	1032:1051	the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies)	1032:1172	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	6	theme	rate	1062:1065	arg1	ratio					1067:1071	Thr/Ser rate ratio	1054:1071	Thr/Ser rate ratio	1054:1071	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	8	7	theme	different	1517:1525	arg1	activities					1536:1545	different relative activities	1517:1545	different relative activities	1517:1545	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	9	8	theme	Thr/Ser	1691:1697	arg1	ratios					1704:1709	the different Thr/Ser rate ratios	1677:1709	the different Thr/Ser rate ratios	1677:1709	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	6	9	theme	substrate	1094:1102	arg1	glycosylation					1104:1116	Thr and Ser substrate glycosylation	1082:1116	glycosylation	1104:1116	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	3	10	theme	O-GalNAc	526:533	arg1	glycosylation					535:547	prior substrate O-GalNAc glycosylation	510:547	prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor	510:624	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	1	11	theme	residues	262:269	arg1	residues					262:269	Ser and Thr residues	250:269	Ser and Thr residues of target substrates	250:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	11	theme	residues	262:269	arg1	groups					240:245	hydroxyl groups	231:245	hydroxyl groups of Ser and Thr residues of target substrates	231:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	11	theme	residues	262:269	arg1	substrates					281:290	target substrates	274:290	target substrates	274:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	0	12	theme	mucin-type	84:93	arg1	O-glycosylation					95:109	mucin-type O-glycosylation	84:109	mucin-type O-glycosylation	84:109	Ser and Thr acceptor preferences of the GalNAc-Ts vary among isoenzymes to modulate mucin-type O-glycosylation.
32304323	7	13	theme	identical	1330:1338	arg1	ratios					1353:1358	nearly identical Thr/Ser rate ratios	1323:1358	nearly identical Thr/Ser rate ratios	1323:1358	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	6	14	with	substrates	967:976	arg1	Ser					998:1000	Ser	998:1000	Ser	998:1000	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	14	with	substrates	967:976	arg1	Thr					991:993	single Thr	984:993	single Thr	984:993	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	15	theme	acceptor	1002:1009	arg1	sites					1011:1015	acceptor sites	1002:1015	acceptor sites	1002:1015	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	7	16	theme	Thr/Ser	1181:1187	arg1	ratios					1194:1199	These Thr/Ser rate ratios	1175:1199	These Thr/Ser rate ratios	1175:1199	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	8	17	theme	activities	1536:1545	arg1	substrates					1503:1512	fixed sequence substrates	1488:1512	fixed sequence substrates of different relative activities	1488:1545	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	3	18	gly	glycosylation	535:547	arg2	sites					552:556	sites	552:556	sites	552:556	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	3	18	gly	glycosylation	535:547	arg1	sites					552:556	sites	552:556	sites	552:556	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	1	19	theme	target	274:279	arg1	substrates					281:290	target substrates	274:290	target substrates	274:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	4	20	theme	own	710:712	arg1	specificity					721:731	its own unique specificity	706:731	its own unique specificity	706:731	Together, these preferences vary among GalNAc-Ts imparting each isoenzyme with its own unique specificity.
32304323	8	21	theme	relative	1527:1534	arg1	activities					1536:1545	different relative activities	1517:1545	different relative activities	1517:1545	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	6	22	theme	Ser	1090:1092	arg1	glycosylation					1104:1116	Thr and Ser substrate glycosylation	1082:1116	glycosylation	1104:1116	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	23	theme	Thr/Ser	1054:1060	arg1	differences					1041:1051	the rate differences	1032:1051	the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies)	1032:1172	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	23	theme	Thr/Ser	1054:1060	arg1	ratio					1067:1071	Thr/Ser rate ratio	1054:1071	Thr/Ser rate ratio	1054:1071	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	9	24	theme	site	1810:1813	arg1	pocket					1815:1820	the active site pocket	1799:1820	the active site pocket	1799:1820	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	3	25	theme	weak	456:459	arg1	motifs					494:499	weak and overlapping peptide sequence motifs	456:499	weak and overlapping peptide sequence motifs	456:499	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	5	26	from	Studies	734:740	arg1	GalNAc-Ts					766:774	the first identified GalNAc-Ts	745:774	the first identified GalNAc-Ts	745:774	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	4	27	theme	unique	714:719	arg1	specificity					721:731	its own unique specificity	706:731	its own unique specificity	706:731	Together, these preferences vary among GalNAc-Ts imparting each isoenzyme with its own unique specificity.
32304323	1	28	theme	mucin-type	178:187	arg1	O-glycosylation					189:203	mucin-type O-glycosylation	178:203	mucin-type O-glycosylation	178:203	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	9	29	theme	group	1782:1786	arg1	strengths					1745:1753	the strengths	1741:1753	the strengths of the Thr acceptor methyl group binding to the active site pocket	1741:1820	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	9	30	theme	methyl	1775:1780	arg1	group					1782:1786	the Thr acceptor methyl group	1758:1786	the Thr acceptor methyl group binding to the active site pocket	1758:1820	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	6	31	theme	Thr	1082:1084	arg1	glycosylation					1104:1116	Thr and Ser substrate glycosylation	1082:1116	glycosylation	1104:1116	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	5	32	theme	GalNAc-T	895:902	arg1	family					904:909	the GalNAc-T family	891:909	the GalNAc-T family	891:909	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	0	33	theme	Ser	0:2	arg1	preferences					21:31	Ser and Thr acceptor preferences	0:31	Ser and Thr acceptor preferences of the GalNAc-Ts	0:48	Ser and Thr acceptor preferences of the GalNAc-Ts vary among isoenzymes to modulate mucin-type O-glycosylation.
32304323	1	34	theme	substrates	281:290	arg1	residues					262:269	Ser and Thr residues	250:269	Ser and Thr residues of target substrates	250:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	34	theme	substrates	281:290	arg1	substrates					281:290	target substrates	274:290	target substrates	274:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	6	35	dep	Thr	991:993	arg1	sites					1011:1015	acceptor sites	1002:1015	acceptor sites	1002:1015	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	36	theme	GalNAc-T	1152:1159	arg1	subfamilies					1161:1171	7 GalNAc-T subfamilies	1150:1171	7 GalNAc-T subfamilies	1150:1171	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	10	37	theme	substrate	1884:1892	arg1	specificity					1894:1904	substrate specificity	1884:1904	substrate specificity	1884:1904	With this work, another activity that further differentiates substrate specificity among the GalNAc-Ts has been identified.
32304323	9	38	theme	GalNAc-T	1656:1663	arg1	structures					1665:1674	GalNAc-T structures	1656:1674	GalNAc-T structures	1656:1674	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	0	39	theme	acceptor	12:19	arg1	preferences					21:31	Ser and Thr acceptor preferences	0:31	Ser and Thr acceptor preferences of the GalNAc-Ts	0:48	Ser and Thr acceptor preferences of the GalNAc-Ts vary among isoenzymes to modulate mucin-type O-glycosylation.
32304323	9	40	theme	rate	1699:1702	arg1	ratios					1704:1709	the different Thr/Ser rate ratios	1677:1709	the different Thr/Ser rate ratios	1677:1709	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	7	41	dep	~18	1247:1249	arg1	to					1244:1245	to	1244:1245	to	1244:1245	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	3	42	theme	sequence	485:492	arg1	motifs					494:499	weak and overlapping peptide sequence motifs	456:499	weak and overlapping peptide sequence motifs	456:499	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	0	43	theme	Thr	8:10	arg1	preferences					21:31	Ser and Thr acceptor preferences	0:31	Ser and Thr acceptor preferences of the GalNAc-Ts	0:48	Ser and Thr acceptor preferences of the GalNAc-Ts vary among isoenzymes to modulate mucin-type O-glycosylation.
32304323	6	44	theme	single	984:989	arg1	Thr					991:993	single Thr	984:993	single Thr	984:993	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	4	45	with	isoenzyme	691:699	arg1	specificity					721:731	its own unique specificity	706:731	its own unique specificity	706:731	Together, these preferences vary among GalNAc-Ts imparting each isoenzyme with its own unique specificity.
32304323	2	46	theme	GalNAc-T	300:307	arg1	isoenzymes					309:318	The 20 GalNAc-T isoenzymes	293:318	The 20 GalNAc-T isoenzymes in humans	293:328	The 20 GalNAc-T isoenzymes in humans are classified into nine subfamilies according to sequence similarity.
32304323	3	47	dep	neighboring	587:597	arg1	short-range					600:610	short-range	600:610	short-range	600:610	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	1	48	theme	GalNAc-transferases	136:154	arg1	family					114:119	A family	112:119	A family of polypeptide GalNAc-transferases (GalNAc-Ts)	112:166	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	5	49	dep	showed	776:781	arg1	preferred					802:810	preferred	802:810	showed Thr acceptors were preferred over Ser acceptors	776:829	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	5	50	theme	Ser	866:868	arg1	glycosylation					870:882	Thr vs. Ser glycosylation	858:882	glycosylation	870:882	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	3	51	theme	overlapping	465:475	arg1	motifs					494:499	weak and overlapping peptide sequence motifs	456:499	weak and overlapping peptide sequence motifs	456:499	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	3	52	theme	glycosylation	433:445	arg1	sites					424:428	their sites	418:428	their sites of glycosylation	418:445	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	3	52	theme	glycosylation	433:445	arg1	glycosylation					433:445	glycosylation	433:445	glycosylation	433:445	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	9	53	theme	Thr	1762:1764	arg1	group					1782:1786	the Thr acceptor methyl group	1758:1786	the Thr acceptor methyl group binding to the active site pocket	1758:1820	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	3	54	theme	peptide	477:483	arg1	motifs					494:499	weak and overlapping peptide sequence motifs	456:499	weak and overlapping peptide sequence motifs	456:499	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	0	55	theme	GalNAc-Ts	40:48	arg1	preferences					21:31	Ser and Thr acceptor preferences	0:31	Ser and Thr acceptor preferences of the GalNAc-Ts	0:48	Ser and Thr acceptor preferences of the GalNAc-Ts vary among isoenzymes to modulate mucin-type O-glycosylation.
32304323	6	56	theme	substrates	967:976	arg1	series					932:937	a series	930:937	a series of identical random peptide substrates, with single Thr or Ser acceptor sites	930:1015	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	5	57	theme	Thr	783:785	arg1	acceptors					787:795	Thr acceptors	783:795	Thr acceptors	783:795	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	6	58	theme	peptide	959:965	arg1	substrates					967:976	identical random peptide substrates	942:976	identical random peptide substrates	942:976	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	8	59	theme	substrates	1503:1512	arg1	series					1478:1483	a series	1476:1483	a series of fixed sequence substrates of different relative activities	1476:1545	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	9	60	theme	different	1681:1689	arg1	ratios					1704:1709	the different Thr/Ser rate ratios	1677:1709	the different Thr/Ser rate ratios	1677:1709	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	9	61	from	differences	1726:1736	arg1	strengths					1745:1753	the strengths	1741:1753	the strengths of the Thr acceptor methyl group binding to the active site pocket	1741:1820	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	3	62	theme	prior	510:514	arg1	glycosylation					535:547	prior substrate O-GalNAc glycosylation	510:547	prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor	510:624	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	6	63	theme	random	952:957	arg1	substrates					967:976	identical random peptide substrates	942:976	identical random peptide substrates	942:976	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	7	64	dep	varied	1201:1206	arg1	GalNAc-T4/GalNAc-T12					1256:1275	GalNAc-T4/GalNAc-T12	1256:1275	GalNAc-T4/GalNAc-T12	1256:1275	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	7	64	dep	varied	1201:1206	arg1	GalNAc-T3/GalNAc-T6					1281:1299	GalNAc-T3/GalNAc-T6	1281:1299	GalNAc-T3/GalNAc-T6	1281:1299	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	8	65	theme	rate	1434:1437	arg1	ratios					1439:1444	the Thr/Ser rate ratios	1422:1444	the Thr/Ser rate ratios	1422:1444	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	3	66	dep	remote	563:568	arg1	long-range					571:580	long-range	571:580	long-range	571:580	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	3	66	dep	remote	563:568	arg1	acceptor					617:624	acceptor	617:624	acceptor	617:624	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	5	67	theme	identified	755:764	arg1	GalNAc-Ts					766:774	the first identified GalNAc-Ts	745:774	the first identified GalNAc-Ts	745:774	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	8	68	theme	fixed	1488:1492	arg1	substrates					1503:1512	fixed sequence substrates	1488:1512	fixed sequence substrates of different relative activities	1488:1545	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	8	69	theme	Thr/Ser	1426:1432	arg1	ratios					1439:1444	the Thr/Ser rate ratios	1422:1444	the Thr/Ser rate ratios	1422:1444	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	7	70	theme	rate	1189:1192	arg1	ratios					1194:1199	These Thr/Ser rate ratios	1175:1199	These Thr/Ser rate ratios	1175:1199	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	1	71	theme	polypeptide	124:134	arg1	GalNAc-Ts					157:165	GalNAc-Ts	157:165	GalNAc-Ts	157:165	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	71	theme	polypeptide	124:134	arg1	GalNAc-transferases					136:154	polypeptide GalNAc-transferases	124:154	polypeptide GalNAc-transferases (GalNAc-Ts)	124:166	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	9	72	theme	active	1803:1808	arg1	pocket					1815:1820	the active site pocket	1799:1820	the active site pocket	1799:1820	Finally, based on GalNAc-T structures, the different Thr/Ser rate ratios likely reflect differences in the strengths of the Thr acceptor methyl group binding to the active site pocket.
32304323	8	73	theme	single	1610:1615	arg1	substrates					1626:1635	single acceptor substrates	1610:1635	single acceptor substrates	1610:1635	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
32304323	1	74	theme	hydroxyl	231:238	arg1	residues					262:269	Ser and Thr residues	250:269	Ser and Thr residues of target substrates	250:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	74	theme	hydroxyl	231:238	arg1	groups					240:245	hydroxyl groups	231:245	hydroxyl groups of Ser and Thr residues of target substrates	231:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	74	theme	hydroxyl	231:238	arg1	substrates					281:290	target substrates	274:290	target substrates	274:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	7	75	theme	rate	1348:1351	arg1	ratios					1353:1358	nearly identical Thr/Ser rate ratios	1323:1358	nearly identical Thr/Ser rate ratios	1323:1358	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	3	76	from	sites	552:556	arg1	glycosylation					535:547	prior substrate O-GalNAc glycosylation	510:547	prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor	510:624	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	3	76	from	sites	552:556	arg1	motifs					494:499	weak and overlapping peptide sequence motifs	456:499	weak and overlapping peptide sequence motifs	456:499	GalNAc-Ts select their sites of glycosylation based on weak and overlapping peptide sequence motifs, as well prior substrate O-GalNAc glycosylation at sites both remote (long-range) and neighboring (short-range) the acceptor.
32304323	2	77	theme	sequence	380:387	arg1	similarity					389:398	sequence similarity	380:398	sequence similarity	380:398	The 20 GalNAc-T isoenzymes in humans are classified into nine subfamilies according to sequence similarity.
32304323	7	78	theme	Thr/Ser	1340:1346	arg1	ratios					1353:1358	nearly identical Thr/Ser rate ratios	1323:1358	nearly identical Thr/Ser rate ratios	1323:1358	These Thr/Ser rate ratios varied across subfamilies, ranging from ~2 to ~18 (for GalNAc-T4/GalNAc-T12 and GalNAc-T3/GalNAc-T6, respectively), while nearly identical Thr/Ser rate ratios were observed for isoenzymes within subfamilies.
32304323	1	79	theme	Ser	250:252	arg1	residues					262:269	Ser and Thr residues	250:269	Ser and Thr residues of target substrates	250:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	1	79	theme	Ser	250:252	arg1	substrates					281:290	target substrates	274:290	target substrates	274:290	A family of polypeptide GalNAc-transferases (GalNAc-Ts) initiates mucin-type O-glycosylation, transferring GalNAc onto hydroxyl groups of Ser and Thr residues of target substrates.
32304323	5	80	theme	Ser	817:819	arg1	acceptors					821:829	Ser acceptors	817:829	Ser acceptors	817:829	Studies on the first identified GalNAc-Ts showed Thr acceptors were preferred over Ser acceptors; however studies comparing Thr vs. Ser glycosylation across the GalNAc-T family are lacking.
32304323	6	81	theme	identical	942:950	arg1	substrates					967:976	identical random peptide substrates	942:976	identical random peptide substrates	942:976	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	82	theme	rate	1036:1039	arg1	differences					1041:1051	the rate differences	1032:1051	the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies)	1032:1172	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	6	82	theme	rate	1036:1039	arg1	ratio					1067:1071	Thr/Ser rate ratio	1054:1071	Thr/Ser rate ratio	1054:1071	Using a series of identical random peptide substrates, with single Thr or Ser acceptor sites, we determined the rate differences (Thr/Ser rate ratio) between Thr and Ser substrate glycosylation for 12 isoenzymes (representing 7 GalNAc-T subfamilies).
32304323	2	83	from	isoenzymes	309:318	arg1	humans					323:328	humans	323:328	humans	323:328	The 20 GalNAc-T isoenzymes in humans are classified into nine subfamilies according to sequence similarity.
32304323	8	84	theme	acceptor	1617:1624	arg1	substrates					1626:1635	single acceptor substrates	1610:1635	single acceptor substrates	1610:1635	Furthermore, the Thr/Ser rate ratios did not appreciably vary over a series of fixed sequence substrates of different relative activities, suggesting the ratio is a constant for each isoenzyme against single acceptor substrates.
34358619	4	0	theme	cell	924:927	arg1	glycoproteins					937:949	cell surface glycoproteins	924:949	cell surface glycoproteins obtained from specific functional brain areas	924:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	6	1	theme	Region-specific	1164:1178	arg1	maps					1187:1190	Region-specific glycan maps	1164:1190	Region-specific glycan maps	1164:1190	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	11	2	from	areas	2349:2353	arg1	disease					2369:2375	disease	2369:2375	disease	2369:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	11	2	from	areas	2349:2353	arg1	health					2358:2363	health	2358:2363	health	2358:2363	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	10	3	theme	discrete	2026:2033	arg1	areas					2067:2071	five discrete anatomical and functional brain areas	2021:2071	five discrete anatomical and functional brain areas	2021:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	4	4	used	used	759:762	arg2	we					756:757	we	756:757	we	756:757	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	11	5	theme	critical	2267:2274	arg1	roles					2287:2291	the critical biological roles	2263:2291	the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease	2263:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	9	6	theme	cortex	1748:1753	arg1	differentiation					1716:1730	the differentiation	1712:1730	the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation	1712:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	6	7	theme	significant	1264:1274	arg1	differences					1276:1286	significant differences	1264:1286	significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species	1264:1386	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	3	8	theme	surface	571:577	arg1	glycoproteins					579:591	numerous cell surface glycoproteins	557:591	numerous cell surface glycoproteins	557:591	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	11	9	theme	specialized	2320:2330	arg1	areas					2349:2353	the specialized functional brain areas	2316:2353	the specialized functional brain areas in health and disease	2316:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	4	10	theme	membrane	893:900	arg1	fractions					902:910	membrane fractions	893:910	membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas	893:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	7	11	theme	cerebral	1495:1502	arg1	cortex					1504:1509	the cerebral cortex	1491:1509	the cerebral cortex	1491:1509	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	11	theme	cerebral	1495:1502	arg1	regions					1451:1457	three functional regions	1434:1457	three functional regions of the forebrain and hindbrain	1434:1488	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	10	12	theme	brain	2061:2065	arg1	areas					2067:2071	five discrete anatomical and functional brain areas	2021:2071	five discrete anatomical and functional brain areas	2021:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	3	13	theme	numerous	557:564	arg1	glycoproteins					579:591	numerous cell surface glycoproteins	557:591	numerous cell surface glycoproteins	557:591	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	11	14	theme	roles	2287:2291	arg1	understanding					2246:2258	a better understanding	2237:2258	a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease	2237:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	6	15	theme	mannose	1327:1333	arg1	bisecting					1336:1344	high mannose, bisecting, and core and antenna fucosylated species	1322:1386	bisecting	1336:1344	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	3	16	theme	current	598:604	arg1	understanding					606:618	our current understanding	594:618	our current understanding of brain glycosylation	594:641	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	4	17	gly	glycoproteins	937:949	arg1	glycoproteins					937:949	cell surface glycoproteins	924:949	cell surface glycoproteins obtained from specific functional brain areas	924:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	11	18	theme	region-specific	2164:2178	arg1	fingerprints					2196:2207	The region-specific molecular glyco fingerprints	2160:2207	The region-specific molecular glyco fingerprints identified here	2160:2223	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	6	19	theme	high	1322:1325	arg1	bisecting					1336:1344	high mannose, bisecting, and core and antenna fucosylated species	1322:1386	bisecting	1336:1344	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	3	20	theme	glycosylation	629:641	arg1	understanding					606:618	our current understanding	594:618	our current understanding of brain glycosylation	594:641	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	1	21	theme	central	235:241	arg1	system					251:256	the central nervous system	231:256	the central nervous system	231:256	N-glycosylation is a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system.
34358619	11	22	theme	better	2239:2244	arg1	understanding					2246:2258	a better understanding	2237:2258	a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease	2237:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	7	23	theme	regions	1451:1457	arg1	N-glycome					1421:1429	the cell membrane N-glycome	1403:1429	the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum,	1403:1539	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	5	24	theme	distinctive	1105:1115	arg1	forebrain					1139:1147	the forebrain	1135:1147	the forebrain	1135:1147	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	5	24	theme	distinctive	1105:1115	arg1	functions					1117:1125	specific and distinctive functions	1092:1125	specific and distinctive functions	1092:1125	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	5	24	theme	distinctive	1105:1115	arg1	hindbrain					1153:1161	hindbrain	1153:1161	hindbrain	1153:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	1	25	theme	ubiquitous	125:134	arg1	modification					154:165	a ubiquitous posttranslational modification	123:165	a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system	123:256	N-glycosylation is a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system.
34358619	1	25	theme	ubiquitous	125:134	arg1	N-glycosylation					104:118	N-glycosylation	104:118	N-glycosylation	104:118	N-glycosylation is a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system.
34358619	4	26	theme	functional	974:983	arg1	areas					991:995	specific functional brain areas	965:995	specific functional brain areas	965:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	10	27	theme	spatial	1943:1949	arg1	distribution					1951:1962	a comprehensive spatial distribution	1927:1962	a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas	1927:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	6	28	theme	brain-type	1292:1301	arg1	glycans					1304:1310	"brain-type" glycans	1291:1310	"brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species	1291:1386	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	6	29	theme	fucosylated	1368:1378	arg1	species					1380:1386	high mannose, bisecting, and core and antenna fucosylated species	1322:1386	species	1380:1386	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	2	30	theme	cell	281:284	arg1	proteins					295:302	cell membrane proteins	281:302	cell membrane proteins	281:302	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	9	31	theme	varying	1841:1847	arg1	degrees					1849:1855	varying degrees	1841:1855	varying degrees of core and antenna fucosylation and sialylation	1841:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	10	32	theme	brain	2134:2138	arg1	glyco-architecture					2140:2157	a previously unknown brain glyco-architecture	2113:2157	a previously unknown brain glyco-architecture	2113:2157	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	0	33	theme	Areas	66:70	arg1	N-Glycome					30:38	Region-Specific Cell Membrane N-Glycome	0:38	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas	0:70	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	6	34	from	differences	1276:1286	arg1	glycans					1304:1310	"brain-type" glycans	1291:1310	"brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species	1291:1386	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	10	35	theme	comprehensive	1929:1941	arg1	distribution					1951:1962	a comprehensive spatial distribution	1927:1962	a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas	1927:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	4	36	theme	glycomic	796:803	arg1	platform					823:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform	764:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory	764:858	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	2	37	theme	crucial	309:315	arg1	roles					317:321	crucial roles	309:321	crucial roles	309:321	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	9	38	theme	fucosylation	1877:1888	arg1	degrees					1849:1855	varying degrees	1841:1855	varying degrees of core and antenna fucosylation and sialylation	1841:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	9	39	with	glycans	1828:1834	arg1	degrees					1849:1855	varying degrees	1841:1855	varying degrees of core and antenna fucosylation and sialylation	1841:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	5	40	theme	major	1043:1047	arg1	divisions					1063:1071	two major developmental divisions	1039:1071	two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain	1039:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	7	41	theme	membrane	1412:1419	arg1	N-glycome					1421:1429	the cell membrane N-glycome	1403:1429	the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum,	1403:1539	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	9	42	theme	sialylation	1894:1904	arg1	degrees					1849:1855	varying degrees	1841:1855	varying degrees of core and antenna fucosylation and sialylation	1841:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	0	43	theme	Region-Specific	0:14	arg1	N-Glycome					30:38	Region-Specific Cell Membrane N-Glycome	0:38	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas	0:70	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	9	44	theme	hippocampus	1756:1766	arg1	differentiation					1716:1730	the differentiation	1712:1730	the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation	1712:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	4	45	theme	cell	783:786	arg1	platform					823:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform	764:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory	764:858	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	0	46	theme	Membrane	21:28	arg1	N-Glycome					30:38	Region-Specific Cell Membrane N-Glycome	0:38	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas	0:70	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	5	47	theme	membrane	1017:1024	arg1	N-glycome					1026:1034	the cell membrane N-glycome	1008:1034	the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain	1008:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	8	48	theme	region-specific	1623:1637	arg1	profiles					1650:1657	their region-specific expression profiles	1617:1657	their region-specific expression profiles	1617:1657	In total, 125 N-glycan compositions were identified, and their region-specific expression profiles were characterized.
34358619	2	49	theme	cell	428:431	arg1	signaling					433:441	cell signaling	428:441	cell signaling	428:441	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	11	50	theme	brain	2343:2347	arg1	areas					2349:2353	the specialized functional brain areas	2316:2353	the specialized functional brain areas in health and disease	2316:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	0	51	theme	Mouse	54:58	arg1	Areas					66:70	Functional Mouse Brain Areas	43:70	Functional Mouse Brain Areas	43:70	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	1	52	theme	nervous	243:249	arg1	system					251:256	the central nervous system	231:256	the central nervous system	231:256	N-glycosylation is a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system.
34358619	5	53	theme	divisions	1063:1071	arg1	N-glycome					1026:1034	the cell membrane N-glycome	1008:1034	the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain	1008:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	3	54	theme	brain	704:708	arg1	regions					710:716	functional brain regions	693:716	functional brain regions	693:716	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	3	55	theme	N-glycosylation	532:546	arg1	state					548:552	the N-glycosylation state	528:552	the N-glycosylation state of numerous cell surface glycoproteins	528:591	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	5	56	theme	mice	1076:1079	arg1	divisions					1063:1071	two major developmental divisions	1039:1071	two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain	1039:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	6	57	theme	glycan	1180:1185	arg1	maps					1187:1190	Region-specific glycan maps	1164:1190	Region-specific glycan maps	1164:1190	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	10	58	theme	anatomical	2035:2044	arg1	areas					2067:2071	five discrete anatomical and functional brain areas	2021:2071	five discrete anatomical and functional brain areas	2021:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	6	59	theme	antenna	1360:1366	arg1	species					1380:1386	high mannose, bisecting, and core and antenna fucosylated species	1322:1386	species	1380:1386	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	9	60	theme	cerebral	1739:1746	arg1	cortex					1748:1753	the cerebral cortex	1735:1753	the cerebral cortex	1735:1753	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	11	61	theme	biological	2276:2285	arg1	roles					2287:2291	the critical biological roles	2263:2291	the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease	2263:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	3	62	theme	cell	566:569	arg1	glycoproteins					579:591	numerous cell surface glycoproteins	557:591	numerous cell surface glycoproteins	557:591	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	4	63	theme	surface	929:935	arg1	glycoproteins					937:949	cell surface glycoproteins	924:949	cell surface glycoproteins obtained from specific functional brain areas	924:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	5	64	with	brain	1081:1085	arg1	forebrain					1139:1147	the forebrain	1135:1147	the forebrain	1135:1147	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	5	64	with	brain	1081:1085	arg1	functions					1117:1125	specific and distinctive functions	1092:1125	specific and distinctive functions	1092:1125	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	5	64	with	brain	1081:1085	arg1	hindbrain					1153:1161	hindbrain	1153:1161	hindbrain	1153:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	10	65	theme	functional	2050:2059	arg1	areas					2067:2071	five discrete anatomical and functional brain areas	2021:2071	five discrete anatomical and functional brain areas	2021:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	11	66	theme	molecular	2180:2188	arg1	fingerprints					2196:2207	The region-specific molecular glyco fingerprints	2160:2207	The region-specific molecular glyco fingerprints identified here	2160:2223	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	6	67	gly	fucosylated	1368:1378	arg1	species					1380:1386	high mannose, bisecting, and core and antenna fucosylated species	1322:1386	species	1380:1386	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	4	68	theme	fractions	902:910	arg1	N-glycome					880:888	the N-glycome	876:888	the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas	876:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	3	69	theme	glycoproteins	579:591	arg1	state					548:552	the N-glycosylation state	528:552	the N-glycosylation state of numerous cell surface glycoproteins	528:591	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	11	70	theme	glyco	2190:2194	arg1	fingerprints					2196:2207	The region-specific molecular glyco fingerprints	2160:2207	The region-specific molecular glyco fingerprints identified here	2160:2223	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	4	71	theme	brain	985:989	arg1	areas					991:995	specific functional brain areas	965:995	specific functional brain areas	965:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	6	72	theme	N-glycan	1216:1223	arg1	compositions					1225:1236	∼120 N-glycan compositions	1211:1236	∼120 N-glycan compositions in each region	1211:1251	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	5	73	dep	mice	1076:1079	arg1	brain					1081:1085	brain	1081:1085	brain	1081:1085	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	9	74	theme	cerebellum	1773:1782	arg1	differentiation					1716:1730	the differentiation	1712:1730	the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation	1712:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	3	75	theme	brain	623:627	arg1	glycosylation					629:641	brain glycosylation	623:641	brain glycosylation	623:641	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	7	76	dep	forebrain	1466:1474	arg1	the					1462:1464	the	1462:1464	the	1462:1464	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	9	77	theme	bisecting	1805:1813	arg1	glycans					1828:1834	bisecting and branched glycans	1805:1834	bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation	1805:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	7	78	theme	forebrain	1466:1474	arg1	cerebellum					1529:1538	cerebellum	1529:1538	cerebellum	1529:1538	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	78	theme	forebrain	1466:1474	arg1	cortex					1504:1509	the cerebral cortex	1491:1509	the cerebral cortex	1491:1509	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	78	theme	forebrain	1466:1474	arg1	regions					1451:1457	three functional regions	1434:1457	three functional regions of the forebrain and hindbrain	1434:1488	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	78	theme	forebrain	1466:1474	arg1	hippocampus					1512:1522	hippocampus	1512:1522	hippocampus	1512:1522	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	9	79	theme	branched	1819:1826	arg1	glycans					1828:1834	bisecting and branched glycans	1805:1834	bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation	1805:1904	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	6	80	theme	"	1302:1302	arg1	glycans					1304:1310	"brain-type" glycans	1291:1310	"brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species	1291:1386	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	2	81	theme	membrane	286:293	arg1	proteins					295:302	cell membrane proteins	281:302	cell membrane proteins	281:302	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	1	82	theme	posttranslational	136:152	arg1	modification					154:165	a ubiquitous posttranslational modification	123:165	a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system	123:256	N-glycosylation is a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system.
34358619	1	82	theme	posttranslational	136:152	arg1	N-glycosylation					104:118	N-glycosylation	104:118	N-glycosylation	104:118	N-glycosylation is a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system.
34358619	4	83	theme	specific	965:972	arg1	areas					991:995	specific functional brain areas	965:995	specific functional brain areas	965:995	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	7	84	theme	functional	1440:1449	arg1	cerebellum					1529:1538	cerebellum	1529:1538	cerebellum	1529:1538	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	84	theme	functional	1440:1449	arg1	cortex					1504:1509	the cerebral cortex	1491:1509	the cerebral cortex	1491:1509	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	84	theme	functional	1440:1449	arg1	regions					1451:1457	three functional regions	1434:1457	three functional regions of the forebrain and hindbrain	1434:1488	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	84	theme	functional	1440:1449	arg1	hippocampus					1512:1522	hippocampus	1512:1522	hippocampus	1512:1522	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	3	85	gly	glycoproteins	579:591	arg1	glycoproteins					579:591	numerous cell surface glycoproteins	557:591	numerous cell surface glycoproteins	557:591	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	10	86	theme	glyco-architecture	2140:2157	arg1	presence					2101:2108	the presence	2097:2108	the presence of a previously unknown brain glyco-architecture	2097:2157	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	2	87	attach	attached	269:276	arg1	proteins					295:302	cell membrane proteins	281:302	cell membrane proteins	281:302	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	2	87	attach	attached	269:276	arg2	N-glycans					259:267	N-glycans	259:267	N-glycans attached to cell membrane proteins	259:302	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	10	88	theme	unknown	2126:2132	arg1	glyco-architecture					2140:2157	a previously unknown brain glyco-architecture	2113:2157	a previously unknown brain glyco-architecture	2113:2157	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	0	89	theme	nanoLC-MS	84:92	arg1	Analysis					94:101	nanoLC-MS Analysis	84:101	nanoLC-MS Analysis	84:101	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	1	90	theme	protein	180:186	arg1	structure					188:196	protein structure	180:196	protein structure	180:196	N-glycosylation is a ubiquitous posttranslational modification that affects protein structure and function, including those of the central nervous system.
34358619	9	91	theme	core	1860:1863	arg1	fucosylation					1877:1888	core and antenna fucosylation	1860:1888	fucosylation	1877:1888	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	8	92	theme	N-glycan	1574:1581	arg1	compositions					1583:1594	125 N-glycan compositions	1570:1594	125 N-glycan compositions	1570:1594	In total, 125 N-glycan compositions were identified, and their region-specific expression profiles were characterized.
34358619	10	93	theme	N-glycomes	1994:2003	arg1	distribution					1951:1962	a comprehensive spatial distribution	1927:1962	a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas	1927:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	7	94	theme	hindbrain	1480:1488	arg1	cerebellum					1529:1538	cerebellum	1529:1538	cerebellum	1529:1538	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	94	theme	hindbrain	1480:1488	arg1	cortex					1504:1509	the cerebral cortex	1491:1509	the cerebral cortex	1491:1509	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	94	theme	hindbrain	1480:1488	arg1	regions					1451:1457	three functional regions	1434:1457	three functional regions of the forebrain and hindbrain	1434:1488	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	7	94	theme	hindbrain	1480:1488	arg1	hippocampus					1512:1522	hippocampus	1512:1522	hippocampus	1512:1522	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	9	95	theme	antenna	1869:1875	arg1	fucosylation					1877:1888	core and antenna fucosylation	1860:1888	fucosylation	1877:1888	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
34358619	4	96	theme	surface	788:794	arg1	platform					823:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform	764:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory	764:858	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	3	97	gly	N-glycosylation	532:546	arg1	glycoproteins					579:591	numerous cell surface glycoproteins	557:591	numerous cell surface glycoproteins	557:591	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	7	98	theme	cell	1407:1410	arg1	N-glycome					1421:1429	the cell membrane N-glycome	1403:1429	the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum,	1403:1539	Additionally, the cell membrane N-glycome of three functional regions of the forebrain and hindbrain, the cerebral cortex, hippocampus, and cerebellum, was characterized.
34358619	4	99	theme	nanoLC-Chip-Q-TOF	805:821	arg1	platform					823:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform	764:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory	764:858	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	3	100	theme	brain	471:475	arg1	function					477:484	brain function	471:484	brain function	471:484	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	0	101	theme	Cell	16:19	arg1	N-Glycome					30:38	Region-Specific Cell Membrane N-Glycome	0:38	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas	0:70	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	11	102	theme	functional	2332:2341	arg1	areas					2349:2353	the specialized functional brain areas	2316:2353	the specialized functional brain areas in health and disease	2316:2375	The region-specific molecular glyco fingerprints identified here will enable a better understanding of the critical biological roles that N-glycans play in the specialized functional brain areas in health and disease.
34358619	10	103	theme	enriched	1985:1992	arg1	N-glycomes					1994:2003	the cell-membrane enriched N-glycomes	1967:2003	the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas	1967:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	6	104	from	compositions	1225:1236	arg1	region					1246:1251	each region	1241:1251	each region	1241:1251	Region-specific glycan maps were obtained with ∼120 N-glycan compositions in each region, revealing significant differences in "brain-type" glycans involving high mannose, bisecting, and core and antenna fucosylated species.
34358619	5	105	theme	cell	1012:1015	arg1	N-glycome					1026:1034	the cell membrane N-glycome	1008:1034	the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain	1008:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	8	106	theme	expression	1639:1648	arg1	profiles					1650:1657	their region-specific expression profiles	1617:1657	their region-specific expression profiles	1617:1657	In total, 125 N-glycan compositions were identified, and their region-specific expression profiles were characterized.
34358619	10	107	theme	cell-membrane	1971:1983	arg1	N-glycomes					1994:2003	the cell-membrane enriched N-glycomes	1967:2003	the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas	1967:2071	This study presents a comprehensive spatial distribution of the cell-membrane enriched N-glycomes associated with five discrete anatomical and functional brain areas, providing evidence for the presence of a previously unknown brain glyco-architecture.
34358619	4	108	theme	well-established	766:781	arg1	platform					823:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform	764:830	a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory	764:858	In this work, we used a well-established cell surface glycomic nanoLC-Chip-Q-TOF platform developed in our laboratory to characterize the N-glycome of membrane fractions enriched in cell surface glycoproteins obtained from specific functional brain areas.
34358619	2	109	theme	cell-cell	388:396	arg1	recognition					398:408	cell-cell recognition	388:408	cell-cell recognition	388:408	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	0	110	theme	Functional	43:52	arg1	Areas					66:70	Functional Mouse Brain Areas	43:70	Functional Mouse Brain Areas	43:70	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	3	111	theme	glycan	659:664	arg1	variations					666:675	glycan variations	659:675	glycan variations associated with functional brain regions	659:716	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	0	112	theme	Brain	60:64	arg1	Areas					66:70	Functional Mouse Brain Areas	43:70	Functional Mouse Brain Areas	43:70	Region-Specific Cell Membrane N-Glycome of Functional Mouse Brain Areas Revealed by nanoLC-MS Analysis.
34358619	5	113	theme	specific	1092:1099	arg1	forebrain					1139:1147	the forebrain	1135:1147	the forebrain	1135:1147	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	5	113	theme	specific	1092:1099	arg1	functions					1117:1125	specific and distinctive functions	1092:1125	specific and distinctive functions	1092:1125	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	5	113	theme	specific	1092:1099	arg1	hindbrain					1153:1161	hindbrain	1153:1161	hindbrain	1153:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	5	114	theme	developmental	1049:1061	arg1	divisions					1063:1071	two major developmental divisions	1039:1071	two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain	1039:1161	We report the cell membrane N-glycome of two major developmental divisions of mice brain with specific and distinctive functions, namely the forebrain and hindbrain.
34358619	3	115	theme	functional	693:702	arg1	regions					710:716	functional brain regions	693:716	functional brain regions	693:716	Although brain function and behavior are known to be regulated by the N-glycosylation state of numerous cell surface glycoproteins, our current understanding of brain glycosylation is limited, and glycan variations associated with functional brain regions remain largely unknown.
34358619	2	116	theme	biology	341:347	arg1	development					375:385	development	375:385	development	375:385	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	2	116	theme	biology	341:347	arg1	recognition					398:408	cell-cell recognition	388:408	cell-cell recognition	388:408	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	2	116	theme	biology	341:347	arg1	embryogenesis					360:372	embryogenesis	360:372	embryogenesis	360:372	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	2	116	theme	biology	341:347	arg1	aspects					330:336	all aspects	326:336	all aspects	326:336	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	2	116	theme	biology	341:347	arg1	signaling					433:441	cell signaling	428:441	cell signaling	428:441	N-glycans attached to cell membrane proteins play crucial roles in all aspects of biology, including embryogenesis, development, cell-cell recognition and adhesion, and cell signaling and communication.
34358619	9	117	dep	cortex	1748:1753	arg1	N-glycome					1784:1792	N-glycome	1784:1792	N-glycome	1784:1792	Over 70 N-glycans contributed to the differentiation of the cerebral cortex, hippocampus, and cerebellum N-glycome, including bisecting and branched glycans with varying degrees of core and antenna fucosylation and sialylation.
32282299	1	0	from	structures	238:247	arg1	controls					286:293	healthy controls	278:293	healthy controls	278:293	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	0	from	structures	238:247	arg1	patients					299:306	patients	299:306	patients with malignant hematological diseases having cytostatic treatment	299:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	8	1	theme	other	1592:1596	arg1	hand					1598:1601	the other hand	1588:1601	the other hand	1588:1601	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	6	2	theme	hematological	1275:1287	arg1	diseases					1289:1296	malignant hematological diseases	1265:1296	malignant hematological diseases having cytostatic treatment	1265:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	3	with	patients	1251:1258	arg1	diseases					1289:1296	malignant hematological diseases	1265:1296	malignant hematological diseases having cytostatic treatment	1265:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	2	4	gly	glycoproteins	458:470	arg1	glycoproteins					458:470	body fluid glycoproteins	447:470	body fluid glycoproteins	447:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	8	5	theme	present	1655:1661	arg1	samples					1643:1649	the serum samples	1633:1649	the serum samples not present in the saliva	1633:1675	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	1	6	theme	IgA	269:271	arg1	structures					238:247	the N-glycosylation structures	218:247	the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	218:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	7	theme	glycosylation	1857:1869	arg1	alterations					1871:1881	IgA glycosylation alterations	1853:1881	IgA glycosylation alterations in serum and saliva	1853:1901	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	9	8	theme	resolution	1737:1746	arg1	methods					1778:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	1	9	theme	fluorescence	174:185	arg1	detection					187:195	laser induced fluorescence detection	160:195	laser induced fluorescence detection (CE-LIF)	160:204	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	9	theme	fluorescence	174:185	arg1	CE-LIF					198:203	CE-LIF	198:203	CE-LIF	198:203	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	10	theme	subjects	1236:1243	arg1	serum					1205:1209	pooled serum	1198:1209	pooled serum	1198:1209	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	10	theme	subjects	1236:1243	arg1	saliva					1215:1220	saliva	1215:1220	saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment	1215:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	11	theme	Z	1158:1158	arg1	profiles					1146:1153	the N-glycosylation profiles	1126:1153	the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	1126:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	12	theme	mucosal	1344:1350	arg1	lesions					1352:1358	induced mild oral mucosal lesions	1326:1358	induced mild oral mucosal lesions	1326:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	13	theme	control	1228:1234	arg1	subjects					1236:1243	10 control subjects	1225:1243	10 control subjects	1225:1243	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	14	theme	mild	1334:1337	arg1	lesions					1352:1358	induced mild oral mucosal lesions	1326:1358	induced mild oral mucosal lesions	1326:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	7	15	theme	31	1378:1379	arg1	RESULTS					1361:1367	RESULTS Eight	1361:1373	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva	1361:1424	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	3	16	theme	major	613:617	arg1	role					619:622	a major role	611:622	a major role in the immune-defense against potential pathogen attacks	611:679	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	6	17	used	used	1110:1113	arg2	electrophoresis					1040:1054	METHODS Capillary electrophoresis	1022:1054	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF)	1022:1104	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	18	theme	malignant	1265:1273	arg1	diseases					1289:1296	malignant hematological diseases	1265:1296	malignant hematological diseases having cytostatic treatment	1265:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	19	from	alterations	1871:1881	arg1	saliva					1896:1901	saliva	1896:1901	saliva	1896:1901	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	9	19	from	alterations	1871:1881	arg1	serum					1886:1890	serum	1886:1890	serum	1886:1890	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	9	20	theme	widespread	1922:1931	arg1	use					1953:1955	widespread molecular medicinal use	1922:1955	widespread molecular medicinal use	1922:1955	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	3	21	theme	potential	654:662	arg1	attacks					673:679	potential pathogen attacks	654:679	potential pathogen attacks	654:679	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	6	22	theme	METHODS	1022:1028	arg1	electrophoresis					1040:1054	METHODS Capillary electrophoresis	1022:1054	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF)	1022:1104	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	23	theme	developed	1693:1701	arg1	partitioning					1711:1722	The developed Z(IgA1) partitioning	1689:1722	The developed Z(IgA1) partitioning	1689:1722	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	8	24	theme	serum	1637:1641	arg1	samples					1643:1649	the serum samples	1633:1649	the serum samples not present in the saliva	1633:1675	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	6	25	theme	pooled	1198:1203	arg1	serum					1205:1209	pooled serum	1198:1209	pooled serum	1198:1209	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	26	theme	medicinal	1943:1951	arg1	use					1953:1955	widespread molecular medicinal use	1922:1955	widespread molecular medicinal use	1922:1955	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	9	27	theme	based	1755:1759	arg1	methods					1778:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	5	28	theme	IgA	878:880	arg1	glycosylation					882:894	IgA glycosylation	878:894	IgA glycosylation	878:894	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	6	29	contain	having	1298:1303	arg2	treatment					1316:1324	cytostatic treatment	1305:1324	cytostatic treatment	1305:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	29	contain	having	1298:1303	arg1	diseases					1289:1296	malignant hematological diseases	1265:1296	malignant hematological diseases having cytostatic treatment	1265:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	2	30	theme	processes	523:531	arg1	indicator					492:500	an effective indicator	479:500	an effective indicator of most inflammatory processes	479:531	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	2	30	theme	processes	523:531	arg1	N-glycosylation					428:442	BACKGROUND Altered N-glycosylation	409:442	BACKGROUND Altered N-glycosylation of body fluid glycoproteins	409:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	8	31	attach	present	1655:1661	arg2	samples					1643:1649	the serum samples	1633:1649	the serum samples not present in the saliva	1633:1675	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	31	attach	present	1655:1661	arg1	saliva					1670:1675	the saliva	1666:1675	the saliva	1666:1675	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	4	32	theme	immunoglobulin	724:737	arg1	sIgA					742:745	sIgA	742:745	sIgA	742:745	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	4	32	theme	immunoglobulin	724:737	arg1	A					739:739	secretory immunoglobulin A	714:739	secretory immunoglobulin A (sIgA)	714:746	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	0	33	theme	Salivary	53:60	arg1	A					77:77	Salivary Immunoglobulin A	53:77	Salivary Immunoglobulin A	53:77	N-glycomic Analysis of Z(IgA1) Partitioned Serum and Salivary Immunoglobulin A by Capillary Electrophoresis.
32282299	1	34	theme	cytostatic	353:362	arg1	treatment					364:372	cytostatic treatment	353:372	cytostatic treatment	353:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	2	35	gly	N-glycosylation	428:442	arg1	glycoproteins					458:470	body fluid glycoproteins	447:470	body fluid glycoproteins	447:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	4	36	theme	prevalent	767:775	arg1	saliva					818:823	saliva	818:823	saliva	818:823	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	4	36	theme	prevalent	767:775	arg1	proteins					777:784	the most prevalent proteins	758:784	the most prevalent proteins	758:784	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	1	37	theme	induced	374:380	arg1	lesions					400:406	induced mild oral mucosal lesions	374:406	induced mild oral mucosal lesions	374:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	5	38	theme	cytostatic	949:958	arg1	treatment					960:968	an administered cytostatic treatment	933:968	an administered cytostatic treatment in patients with malignant hematological disorders	933:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	6	39	gly	N-glycosylation	1130:1144	arg1	IgA1					1160:1163	IgA1	1160:1163	IgA1	1160:1163	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	39	gly	N-glycosylation	1130:1144	arg1	Z					1158:1158	Z	1158:1158	Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	1158:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	2	40	theme	Altered	420:426	arg1	indicator					492:500	an effective indicator	479:500	an effective indicator of most inflammatory processes	479:531	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	2	40	theme	Altered	420:426	arg1	N-glycosylation					428:442	BACKGROUND Altered N-glycosylation	409:442	BACKGROUND Altered N-glycosylation of body fluid glycoproteins	409:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	0	41	theme	Capillary	82:90	arg1	Electrophoresis					92:106	Capillary Electrophoresis	82:106	Capillary Electrophoresis	82:106	N-glycomic Analysis of Z(IgA1) Partitioned Serum and Salivary Immunoglobulin A by Capillary Electrophoresis.
32282299	1	42	theme	oral	387:390	arg1	lesions					400:406	induced mild oral mucosal lesions	374:406	induced mild oral mucosal lesions	374:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	43	theme	glyocoanalytical	1761:1776	arg1	methods					1778:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	9	44	theme	high	1732:1735	arg1	methods					1778:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	0	45	theme	N-glycomic	0:9	arg1	Analysis					11:18	N-glycomic Analysis	0:18	N-glycomic Analysis of Z(IgA1)	0:29	N-glycomic Analysis of Z(IgA1) Partitioned Serum and Salivary Immunoglobulin A by Capillary Electrophoresis.
32282299	6	46	theme	patients	1251:1258	arg1	serum					1205:1209	pooled serum	1198:1209	pooled serum	1198:1209	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	46	theme	patients	1251:1258	arg1	saliva					1215:1220	saliva	1215:1220	saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment	1215:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	7	47	from	31	1378:1379	arg1	saliva					1419:1424	saliva	1419:1424	saliva	1419:1424	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	7	47	from	31	1378:1379	arg1	serum					1409:1413	serum	1409:1413	serum	1409:1413	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	6	48	theme	fluorescent	1075:1085	arg1	detection					1087:1095	laser induced fluorescent detection	1061:1095	laser induced fluorescent detection (CE-LIF)	1061:1104	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	48	theme	fluorescent	1075:1085	arg1	CE-LIF					1098:1103	CE-LIF	1098:1103	CE-LIF	1098:1103	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	49	theme	CE-LIF	1748:1753	arg1	methods					1778:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	the high resolution CE-LIF based glyocoanalytical methods	1728:1784	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	2	50	theme	fluid	452:456	arg1	glycoproteins					458:470	body fluid glycoproteins	447:470	body fluid glycoproteins	447:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	1	51	theme	capillary	129:137	arg1	electrophoresis					139:153	capillary electrophoresis	129:153	capillary electrophoresis	129:153	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	2	52	theme	most	505:508	arg1	processes					523:531	most inflammatory processes	505:531	most inflammatory processes	505:531	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	8	53	from	present	1655:1661	arg1	saliva					1670:1675	the saliva	1666:1675	the saliva	1666:1675	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	1	54	theme	malignant	313:321	arg1	diseases					337:344	malignant hematological diseases	313:344	malignant hematological diseases having cytostatic treatment	313:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	55	theme	N-glycosylation	1130:1144	arg1	profiles					1146:1153	the N-glycosylation profiles	1126:1153	the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	1126:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	56	theme	efficient	1798:1806	arg1	workflow					1822:1829	an efficient and sensitive workflow	1795:1829	an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use	1795:1955	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	1	57	contain	having	346:351	arg1	diseases					337:344	malignant hematological diseases	313:344	malignant hematological diseases having cytostatic treatment	313:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	57	contain	having	346:351	arg2	treatment					364:372	cytostatic treatment	353:372	cytostatic treatment	353:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	58	theme	electrophoresis	139:153	arg1	Application					114:124	Application	114:124	Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF)	114:204	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	59	theme	sensitive	1812:1820	arg1	workflow					1822:1829	an efficient and sensitive workflow	1795:1829	an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use	1795:1955	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	5	60	dep	OBJECTIVE	826:834	arg1	was					844:846	was	844:846	was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders	844:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	5	61	theme	hematological	997:1009	arg1	disorders					1011:1019	malignant hematological disorders	987:1019	malignant hematological disorders	987:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	8	62	from	present	1541:1547	arg1	serum					1578:1582	the serum	1574:1582	the serum	1574:1582	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	62	from	present	1541:1547	arg1	saliva					1556:1561	the saliva	1552:1561	the saliva	1552:1561	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	5	63	with	patients	973:980	arg1	disorders					1011:1019	malignant hematological disorders	987:1019	malignant hematological disorders	987:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	6	64	with	subjects	1236:1243	arg1	diseases					1289:1296	malignant hematological diseases	1265:1296	malignant hematological diseases having cytostatic treatment	1265:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	65	theme	serum	252:256	arg1	IgA					269:271	serum and saliva IgA	252:271	IgA	269:271	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	66	from	patients	299:306	arg1	structures					238:247	the N-glycosylation structures	218:247	the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	218:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	66	from	patients	299:306	arg1	IgA					269:271	serum and saliva IgA	252:271	IgA	269:271	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	3	67	theme	second	564:569	arg1	immunoglobulin					588:601	the second highest abundant immunoglobulin	560:601	the second highest abundant immunoglobulin	560:601	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	67	theme	second	564:569	arg1	A					549:549	Immunoglobulin A	534:549	Immunoglobulin A (IgA)	534:555	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	4	68	from	serum	707:711	arg1	abundant					695:702	abundant	695:702	abundant	695:702	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	1	69	theme	saliva	262:267	arg1	IgA					269:271	serum and saliva IgA	252:271	IgA	269:271	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	7	70	theme	significant	1448:1458	arg1	differences					1469:1479	significant (p<0.05) differences	1448:1479	significant (p<0.05) differences	1448:1479	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	1	71	with	patients	299:306	arg1	diseases					337:344	malignant hematological diseases	313:344	malignant hematological diseases having cytostatic treatment	313:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	72	theme	immunoglobulin	1178:1191	arg1	A					1193:1193	immunoglobulin A	1178:1193	immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	1178:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	73	theme	IgA	1853:1855	arg1	alterations					1871:1881	IgA glycosylation alterations	1853:1881	IgA glycosylation alterations in serum and saliva	1853:1901	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	1	74	from	controls	286:293	arg1	structures					238:247	the N-glycosylation structures	218:247	the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	218:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	74	from	controls	286:293	arg1	IgA					269:271	serum and saliva IgA	252:271	IgA	269:271	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	4	75	from	abundant	695:702	arg1	serum					707:711	serum	707:711	serum	707:711	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	1	76	theme	induced	166:172	arg1	detection					187:195	laser induced fluorescence detection	160:195	laser induced fluorescence detection (CE-LIF)	160:204	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	76	theme	induced	166:172	arg1	CE-LIF					198:203	CE-LIF	198:203	CE-LIF	198:203	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	77	with	controls	286:293	arg1	diseases					337:344	malignant hematological diseases	313:344	malignant hematological diseases having cytostatic treatment	313:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	7	78	dep	significant	1448:1458	arg1	p<0.05					1461:1466	p<0.05	1461:1466	p<0.05	1461:1466	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	9	79	theme	IgA1	1705:1708	arg1	partitioning					1711:1722	The developed Z(IgA1) partitioning	1689:1722	The developed Z(IgA1) partitioning	1689:1722	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	8	80	from	saliva	1556:1561	arg1	present					1541:1547	present	1541:1547	present	1541:1547	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	3	81	theme	abundant	579:586	arg1	immunoglobulin					588:601	the second highest abundant immunoglobulin	560:601	the second highest abundant immunoglobulin	560:601	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	81	theme	abundant	579:586	arg1	A					549:549	Immunoglobulin A	534:549	Immunoglobulin A (IgA)	534:555	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	7	82	theme	N-glycans	1396:1404	arg1	N-glycans					1396:1404	38 N-glycans	1393:1404	38 N-glycans	1393:1404	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	7	82	theme	N-glycans	1396:1404	arg1	31					1378:1379	31	1378:1379	31	1378:1379	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	6	83	theme	oral	1339:1342	arg1	lesions					1352:1358	induced mild oral mucosal lesions	1326:1358	induced mild oral mucosal lesions	1326:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	84	theme	induced	1326:1332	arg1	lesions					1352:1358	induced mild oral mucosal lesions	1326:1358	induced mild oral mucosal lesions	1326:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	8	85	attach	present	1541:1547	arg2	glycans					1528:1534	Thirteen glycans	1519:1534	Thirteen glycans	1519:1534	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	85	attach	present	1541:1547	arg1	serum					1578:1582	the serum	1574:1582	the serum	1574:1582	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	85	attach	present	1541:1547	arg1	saliva					1556:1561	the saliva	1552:1561	the saliva	1552:1561	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	7	86	theme	control	1504:1510	arg1	group					1512:1516	the control group	1500:1516	the control group	1500:1516	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	6	87	theme	cytostatic	1305:1314	arg1	treatment					1316:1324	cytostatic treatment	1305:1324	cytostatic treatment	1305:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	88	theme	Capillary	1030:1038	arg1	electrophoresis					1040:1054	METHODS Capillary electrophoresis	1022:1054	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF)	1022:1104	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	9	89	theme	molecular	1933:1941	arg1	use					1953:1955	widespread molecular medicinal use	1922:1955	widespread molecular medicinal use	1922:1955	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	6	90	dep	serum	1205:1209	arg1	lesions					1352:1358	induced mild oral mucosal lesions	1326:1358	induced mild oral mucosal lesions	1326:1358	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	5	91	from	changes	867:873	arg1	saliva					909:914	saliva	909:914	saliva	909:914	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	5	91	from	changes	867:873	arg1	serum					899:903	serum	899:903	serum	899:903	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	3	92	dep	abundant	579:586	arg1	highest					571:577	highest	571:577	highest	571:577	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	7	93	from	serum	1409:1413	arg1	RESULTS					1361:1367	RESULTS Eight	1361:1373	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva	1361:1424	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	9	94	theme	Z	1703:1703	arg1	partitioning					1711:1722	The developed Z(IgA1) partitioning	1689:1722	The developed Z(IgA1) partitioning	1689:1722	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	1	95	dep	controls	286:293	arg1	lesions					400:406	induced mild oral mucosal lesions	374:406	induced mild oral mucosal lesions	374:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	0	96	theme	Immunoglobulin	62:75	arg1	A					77:77	Salivary Immunoglobulin A	53:77	Salivary Immunoglobulin A	53:77	N-glycomic Analysis of Z(IgA1) Partitioned Serum and Salivary Immunoglobulin A by Capillary Electrophoresis.
32282299	5	97	theme	glycosylation	882:894	arg1	response					921:928	a response	919:928	a response to an administered cytostatic treatment in patients with malignant hematological disorders	919:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	5	97	theme	glycosylation	882:894	arg1	changes					867:873	the changes	863:873	the changes of IgA glycosylation in serum and saliva	863:914	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	7	98	from	saliva	1419:1424	arg1	RESULTS					1361:1367	RESULTS Eight	1361:1373	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva	1361:1424	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	2	99	theme	inflammatory	510:521	arg1	processes					523:531	most inflammatory processes	505:531	most inflammatory processes	505:531	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	4	100	theme	secretory	714:722	arg1	sIgA					742:745	sIgA	742:745	sIgA	742:745	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	4	100	theme	secretory	714:722	arg1	A					739:739	secretory immunoglobulin A	714:739	secretory immunoglobulin A (sIgA)	714:746	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	9	101	dep	CONCLUSION	1678:1687	arg1	provided					1786:1793	provided	1786:1793	provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use	1786:1955	CONCLUSION The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
32282299	4	102	from	proteins	777:784	arg1	surfaces					797:804	mucosal surfaces	789:804	mucosal surfaces	789:804	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	5	103	theme	administered	936:947	arg1	treatment					960:968	an administered cytostatic treatment	933:968	an administered cytostatic treatment in patients with malignant hematological disorders	933:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	1	104	theme	mild	382:385	arg1	lesions					400:406	induced mild oral mucosal lesions	374:406	induced mild oral mucosal lesions	374:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	105	with	Application	114:124	arg1	detection					187:195	laser induced fluorescence detection	160:195	laser induced fluorescence detection (CE-LIF)	160:204	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	1	105	with	Application	114:124	arg1	CE-LIF					198:203	CE-LIF	198:203	CE-LIF	198:203	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	7	106	from	RESULTS	1361:1367	arg1	saliva					1419:1424	saliva	1419:1424	saliva	1419:1424	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	7	106	from	RESULTS	1361:1367	arg1	serum					1409:1413	serum	1409:1413	serum	1409:1413	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	4	107	theme	proteins	777:784	arg1	saliva					818:823	saliva	818:823	saliva	818:823	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	4	107	theme	proteins	777:784	arg1	proteins					777:784	the most prevalent proteins	758:784	the most prevalent proteins	758:784	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	4	107	theme	proteins	777:784	arg1	one					751:753	one	751:753	one	751:753	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	6	108	from	A	1193:1193	arg1	serum					1205:1209	pooled serum	1198:1209	pooled serum	1198:1209	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	108	from	A	1193:1193	arg1	saliva					1215:1220	saliva	1215:1220	saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment	1215:1324	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	2	109	theme	BACKGROUND	409:418	arg1	indicator					492:500	an effective indicator	479:500	an effective indicator of most inflammatory processes	479:531	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	2	109	theme	BACKGROUND	409:418	arg1	N-glycosylation					428:442	BACKGROUND Altered N-glycosylation	409:442	BACKGROUND Altered N-glycosylation of body fluid glycoproteins	409:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	1	110	theme	mucosal	392:398	arg1	lesions					400:406	induced mild oral mucosal lesions	374:406	induced mild oral mucosal lesions	374:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	8	111	from	serum	1578:1582	arg1	present					1541:1547	present	1541:1547	present	1541:1547	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	0	112	theme	Z	23:23	arg1	Analysis					11:18	N-glycomic Analysis	0:18	N-glycomic Analysis of Z(IgA1)	0:29	N-glycomic Analysis of Z(IgA1) Partitioned Serum and Salivary Immunoglobulin A by Capillary Electrophoresis.
32282299	1	113	theme	healthy	278:284	arg1	controls					286:293	healthy controls	278:293	healthy controls	278:293	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	7	114	theme	four	1385:1388	arg1	RESULTS					1361:1367	RESULTS Eight	1361:1373	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva	1361:1424	RESULTS Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group.
32282299	6	115	theme	induced	1067:1073	arg1	detection					1087:1095	laser induced fluorescent detection	1061:1095	laser induced fluorescent detection (CE-LIF)	1061:1104	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	115	theme	induced	1067:1073	arg1	CE-LIF					1098:1103	CE-LIF	1098:1103	CE-LIF	1098:1103	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	2	116	theme	glycoproteins	458:470	arg1	indicator					492:500	an effective indicator	479:500	an effective indicator of most inflammatory processes	479:531	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	2	116	theme	glycoproteins	458:470	arg1	N-glycosylation					428:442	BACKGROUND Altered N-glycosylation	409:442	BACKGROUND Altered N-glycosylation of body fluid glycoproteins	409:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	3	117	contain	has	607:609	arg1	immunoglobulin					588:601	the second highest abundant immunoglobulin	560:601	the second highest abundant immunoglobulin	560:601	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	117	contain	has	607:609	arg1	IgA					552:554	IgA	552:554	IgA	552:554	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	117	contain	has	607:609	arg1	A					549:549	Immunoglobulin A	534:549	Immunoglobulin A (IgA)	534:555	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	117	contain	has	607:609	arg2	role					619:622	a major role	611:622	a major role in the immune-defense against potential pathogen attacks	611:679	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	118	from	role	619:622	arg1	immune-defense					631:644	the immune-defense	627:644	the immune-defense	627:644	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	2	119	theme	body	447:450	arg1	glycoproteins					458:470	body fluid glycoproteins	447:470	body fluid glycoproteins	447:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	3	120	theme	pathogen	664:671	arg1	attacks					673:679	potential pathogen attacks	654:679	potential pathogen attacks	654:679	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	8	121	located	found	1624:1628	arg1	hand					1598:1601	the other hand	1588:1601	the other hand	1588:1601	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	121	located	found	1624:1628	arg2	structures					1608:1617	six structures	1604:1617	six structures	1604:1617	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	121	located	found	1624:1628	arg1	samples					1643:1649	the serum samples	1633:1649	the serum samples not present in the saliva	1633:1675	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	122	located	present	1541:1547	arg2	glycans					1528:1534	Thirteen glycans	1519:1534	Thirteen glycans	1519:1534	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	8	122	located	present	1541:1547	arg1	saliva					1556:1561	the saliva	1552:1561	the saliva	1552:1561	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	2	123	theme	effective	482:490	arg1	indicator					492:500	an effective indicator	479:500	an effective indicator of most inflammatory processes	479:531	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	2	123	theme	effective	482:490	arg1	N-glycosylation					428:442	BACKGROUND Altered N-glycosylation	409:442	BACKGROUND Altered N-glycosylation of body fluid glycoproteins	409:470	BACKGROUND Altered N-glycosylation of body fluid glycoproteins can be an effective indicator of most inflammatory processes.
32282299	3	124	theme	Immunoglobulin	534:547	arg1	immunoglobulin					588:601	the second highest abundant immunoglobulin	560:601	the second highest abundant immunoglobulin	560:601	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	124	theme	Immunoglobulin	534:547	arg1	IgA					552:554	IgA	552:554	IgA	552:554	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	3	124	theme	Immunoglobulin	534:547	arg1	A					549:549	Immunoglobulin A	534:549	Immunoglobulin A (IgA)	534:555	Immunoglobulin A (IgA) is the second highest abundant immunoglobulin and has a major role in the immune-defense against potential pathogen attacks.
32282299	1	125	theme	hematological	323:335	arg1	diseases					337:344	malignant hematological diseases	313:344	malignant hematological diseases having cytostatic treatment	313:372	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	126	with	electrophoresis	1040:1054	arg1	detection					1087:1095	laser induced fluorescent detection	1061:1095	laser induced fluorescent detection (CE-LIF)	1061:1104	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	6	126	with	electrophoresis	1040:1054	arg1	CE-LIF					1098:1103	CE-LIF	1098:1103	CE-LIF	1098:1103	METHODS Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	4	127	theme	mucosal	789:795	arg1	surfaces					797:804	mucosal surfaces	789:804	mucosal surfaces	789:804	While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces, such as in saliva.
32282299	1	128	theme	N-glycosylation	222:236	arg1	structures					238:247	the N-glycosylation structures	218:247	the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions	218:406	AIMS Application of capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions.
32282299	5	129	theme	malignant	987:995	arg1	disorders					1011:1019	malignant hematological disorders	987:1019	malignant hematological disorders	987:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32282299	8	130	from	saliva	1670:1675	arg1	present					1655:1661	present	1655:1661	present	1655:1661	Thirteen glycans were present in the saliva but not in the serum, on the other hand, six structures were found in the serum samples not present in the saliva.
32282299	5	131	from	treatment	960:968	arg1	patients					973:980	patients	973:980	patients with malignant hematological disorders	973:1019	OBJECTIVE Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders.
32782472	5	0	dep	RESULTS	841:847	arg1	hosts					864:868	Two expression hosts	849:868	Two expression hosts	849:868	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	0	dep	RESULTS	841:847	arg1	oryzae					883:888	Aspergillus oryzae	871:888	Aspergillus oryzae	871:888	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	0	dep	RESULTS	841:847	arg1	reesei					906:911	Trichoderma reesei	894:911	Trichoderma reesei	894:911	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	7	1	theme	steady-state	1223:1234	arg1	kinetics					1236:1243	steady-state kinetics	1223:1243	steady-state kinetics	1223:1243	The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates.
32782472	1	2	theme	biomass	287:293	arg1	degradation					295:305	lignocellulosic biomass degradation	271:305	lignocellulosic biomass degradation	271:305	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	9	3	theme	cellulose	1625:1633	arg1	surface					1635:1641	the cellulose surface	1621:1641	the cellulose surface	1621:1641	The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates.
32782472	0	4	link	N-linked	11:18	arg1	glycans					20:26	N-linked glycans	11:26	N-linked glycans in cellobiohydrolase Cel7A	11:53	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	4	5	theme	expression	654:663	arg1	host					665:668	the fungal expression host	643:668	the fungal expression host	643:668	Depending on the fungal expression host, glycosylation can vary not only in glycoforms, but also in site occupancy, leading to a complex pattern of glycans, which can affect the enzyme's stability and kinetics.
32782472	11	6	theme	higher	1952:1957	arg1	number					1959:1964	higher number	1952:1964	higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384	1952:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	14	7	from	enzyme	2534:2539	arg1	substrates					2579:2588	the insoluble substrates	2565:2588	the insoluble substrates	2565:2588	This knowledge could be applied to modify enzyme glycosylation to engineer enzyme with higher activity on the insoluble substrates.
32782472	10	8	theme	triple	1857:1862	arg1	enzyme					1874:1879	the triple deficient enzyme	1853:1879	the triple deficient enzyme	1853:1879	Thus, site density (number of sites per gram cellulose) was 30-60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme.
32782472	9	9	theme	similar	1654:1660	arg1	pattern					1662:1668	a similar pattern	1652:1668	a similar pattern on all tested substrates	1652:1693	The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates.
32782472	12	10	theme	kinetic	2077:2083	arg1	changes					2085:2091	The kinetic changes	2073:2091	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans	2061:2141	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	8	11	with	variants	1412:1419	arg1	content					1450:1456	reduced N-glycosylation content	1426:1456	reduced N-glycosylation content	1426:1456	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	8	12	from	substrates	1545:1554	arg1	half					1514:1517	half	1514:1517	half of the WTs' value on some substrates	1514:1554	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	0	13	from	affinity	115:122	arg1	cellulose					139:147	crystalline cellulose	127:147	crystalline cellulose	127:147	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	9	14	from	pattern	1662:1668	arg1	substrates					1684:1693	all tested substrates	1673:1693	all tested substrates	1673:1693	The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates.
32782472	11	15	theme	crystal	2003:2009	arg1	cellulose					1993:2001	cellulose	1993:2001	cellulose crystal upon removal of glycans at position N45 and N384	1993:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	10	16	theme	sites	1726:1730	arg1	number					1716:1721	number	1716:1721	number of sites per gram cellulose	1716:1749	Thus, site density (number of sites per gram cellulose) was 30-60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme.
32782472	1	17	theme	major	218:222	arg1	Cellobiohydrolase					161:177	BACKGROUND Cellobiohydrolase	150:177	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7	150:211	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	1	17	theme	major	218:222	arg1	component					224:232	a major component	216:232	a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation	216:305	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	9	18	theme	tested	1677:1682	arg1	substrates					1684:1693	all tested substrates	1673:1693	all tested substrates	1673:1693	The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates.
32782472	11	19	from	position	2038:2045	arg1	glycans					2027:2033	glycans	2027:2033	glycans at position N45 and N384	2027:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	11	19	from	position	2038:2045	arg1	removal					2016:2022	removal	2016:2022	removal of glycans at position N45 and N384	2016:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	5	20	used	utilized	919:926	arg2	RESULTS					841:847	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei,	841:912	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei,	841:912	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	11	21	theme	contacts	1969:1976	arg1	number					1959:1964	higher number	1952:1964	higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384	1952:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	13	22	theme	site	2279:2282	arg1	density					2284:2290	attack site density	2272:2290	attack site density of TrCel7A	2272:2301	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	11	23	theme	glycans	2027:2033	arg1	removal					2016:2022	removal	2016:2022	removal of glycans at position N45 and N384	2016:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	2	24	dep	reesei	336:341	arg1	TrCel7A					350:356	TrCel7A	350:356	TrCel7A	350:356	For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases.
32782472	11	25	theme	Molecular	1882:1890	arg1	simulation					1900:1909	Molecular dynamic simulation	1882:1909	Molecular dynamic simulation of the N-glycan mutants TrCel7A	1882:1941	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	14	26	theme	insoluble	2569:2577	arg1	substrates					2579:2588	the insoluble substrates	2565:2588	the insoluble substrates	2565:2588	This knowledge could be applied to modify enzyme glycosylation to engineer enzyme with higher activity on the insoluble substrates.
32782472	8	27	theme	triple	1471:1476	arg1	mutants					1488:1494	the triple deficient mutants	1467:1494	the triple deficient mutants	1467:1494	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	4	28	theme	complex	759:765	arg1	pattern					767:773	a complex pattern	757:773	a complex pattern	757:773	Depending on the fungal expression host, glycosylation can vary not only in glycoforms, but also in site occupancy, leading to a complex pattern of glycans, which can affect the enzyme's stability and kinetics.
32782472	11	29	from	removal	2016:2022	arg1	position					2038:2045	position N45 and N384	2038:2058	position	2038:2045	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	11	29	from	removal	2016:2022	arg1	N384					2055:2058	N384	2055:2058	N384	2055:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	11	30	theme	mutants	1927:1933	arg1	simulation					1900:1909	Molecular dynamic simulation	1882:1909	Molecular dynamic simulation of the N-glycan mutants TrCel7A	1882:1941	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	3	31	dep	flexible	597:604	arg1	O-glycosylated					607:620	O-glycosylated	607:620	O-glycosylated	607:620	The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker.
32782472	0	32	from	activity	94:101	arg1	cellulose					139:147	crystalline cellulose	127:147	crystalline cellulose	127:147	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	4	33	theme	site	730:733	arg1	occupancy					735:743	site occupancy	730:743	site occupancy	730:743	Depending on the fungal expression host, glycosylation can vary not only in glycoforms, but also in site occupancy, leading to a complex pattern of glycans, which can affect the enzyme's stability and kinetics.
32782472	0	34	theme	Trichoderma	60:70	arg1	reesei					72:77	Trichoderma reesei	60:77	Trichoderma reesei	60:77	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	14	35	theme	higher	2546:2551	arg1	activity					2553:2560	higher activity	2546:2560	higher activity	2546:2560	This knowledge could be applied to modify enzyme glycosylation to engineer enzyme with higher activity on the insoluble substrates.
32782472	1	36	theme	glycoside	184:192	arg1	family					204:209	glycoside hydrolase family 7	184:211	glycoside hydrolase family 7	184:211	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	0	37	from	Removal	0:6	arg1	Cel7A					49:53	cellobiohydrolase Cel7A	31:53	cellobiohydrolase Cel7A	31:53	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	12	38	theme	accessibility	2180:2192	arg1	modifications					2153:2165	modifications	2153:2165	modifications of substrate accessibility	2153:2192	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	7	39	theme	TrCel7A	1191:1197	arg1	enzymes					1199:1205	The TrCel7A enzymes	1187:1205	The TrCel7A enzymes	1187:1205	The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates.
32782472	0	40	from	Cel7A	49:53	arg1	Removal					0:6	Removal	0:6	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei	0:77	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	3	41	theme	TrCel7A	482:488	arg1	architecture					466:477	The architecture	462:477	The architecture of TrCel7A	462:488	The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker.
32782472	0	42	theme	binding	107:113	arg1	affinity					115:122	binding affinity	107:122	binding affinity	107:122	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	5	43	theme	triple	992:997	arg1	ΔN-glyc					1078:1084	ΔN-glyc	1078:1084	ΔN-glyc	1078:1084	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	43	theme	triple	992:997	arg1	mutants					1030:1036	the triple N-glycosylation site deficient mutants	988:1036	the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc )	988:1086	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	43	theme	triple	992:997	arg1	ΔN-glyc					1066:1072	ΔN-glyc	1066:1072	ΔN-glyc	1066:1072	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	2	44	theme	structure-function	395:412	arg1	relationships					414:426	structure-function relationships	395:426	structure-function relationships of processive cellobiohydrolases	395:459	For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases.
32782472	3	45	theme	catalytic	517:525	arg1	domain					527:532	an N-glycosylated catalytic domain	499:532	an N-glycosylated catalytic domain	499:532	The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker.
32782472	0	46	theme	N-linked	11:18	arg1	glycans					20:26	N-linked glycans	11:26	N-linked glycans in cellobiohydrolase Cel7A	11:53	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	2	47	theme	cellobiohydrolases	442:459	arg1	relationships					414:426	structure-function relationships	395:426	structure-function relationships of processive cellobiohydrolases	395:459	For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases.
32782472	7	48	theme	different	1306:1314	arg1	substrates					1327:1336	different cellulosic substrates	1306:1336	different cellulosic substrates	1306:1336	The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates.
32782472	10	49	theme	deficient	1785:1793	arg1	variants					1795:1802	the single deficient variants	1774:1802	the single deficient variants compared to the WT	1774:1821	Thus, site density (number of sites per gram cellulose) was 30-60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme.
32782472	3	50	gly	N-glycosylated	502:515	arg1	domain					527:532	an N-glycosylated catalytic domain	499:532	an N-glycosylated catalytic domain	499:532	The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker.
32782472	8	51	from	half	1514:1517	arg1	substrates					1545:1554	some substrates	1540:1554	some substrates	1540:1554	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	8	52	theme	reduced	1426:1432	arg1	content					1450:1456	reduced N-glycosylation content	1426:1456	reduced N-glycosylation content	1426:1456	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	1	53	theme	commercial	237:246	arg1	mixtures					258:265	commercial enzymatic mixtures	237:265	commercial enzymatic mixtures	237:265	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	5	54	theme	site	1015:1018	arg1	ΔN-glyc					1078:1084	ΔN-glyc	1078:1084	ΔN-glyc	1078:1084	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	54	theme	site	1015:1018	arg1	mutants					1030:1036	the triple N-glycosylation site deficient mutants	988:1036	the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc )	988:1086	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	54	theme	site	1015:1018	arg1	ΔN-glyc					1066:1072	ΔN-glyc	1066:1072	ΔN-glyc	1066:1072	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	6	55	theme	single	1108:1113	arg1	mutants					1146:1152	single N-glycosylation site deficient mutants	1108:1152	single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q )	1108:1184	Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q ).
32782472	2	56	theme	processive	431:440	arg1	cellobiohydrolases					442:459	processive cellobiohydrolases	431:459	processive cellobiohydrolases	431:459	For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases.
32782472	3	57	theme	carbohydrate-binding	559:578	arg1	module					580:585	a carbohydrate-binding module	557:585	a carbohydrate-binding module	557:585	The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker.
32782472	1	58	theme	mixtures	258:265	arg1	Cellobiohydrolase					161:177	BACKGROUND Cellobiohydrolase	150:177	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7	150:211	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	1	58	theme	mixtures	258:265	arg1	component					224:232	a major component	216:232	a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation	216:305	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	1	59	theme	lignocellulosic	271:285	arg1	degradation					295:305	lignocellulosic biomass degradation	271:305	lignocellulosic biomass degradation	271:305	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	14	60	with	enzyme	2534:2539	arg1	activity					2553:2560	higher activity	2546:2560	higher activity	2546:2560	This knowledge could be applied to modify enzyme glycosylation to engineer enzyme with higher activity on the insoluble substrates.
32782472	8	61	from	value	1531:1535	arg1	substrates					1545:1554	some substrates	1540:1554	some substrates	1540:1554	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	12	62	theme	N-linked	2126:2133	arg1	glycans					2135:2141	N-linked glycans	2126:2141	N-linked glycans	2126:2141	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	3	63	theme	flexible	597:604	arg1	linker					622:627	a flexible, O-glycosylated linker	595:627	a flexible, O-glycosylated linker	595:627	The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker.
32782472	4	64	theme	fungal	647:652	arg1	host					665:668	the fungal expression host	643:668	the fungal expression host	643:668	Depending on the fungal expression host, glycosylation can vary not only in glycoforms, but also in site occupancy, leading to a complex pattern of glycans, which can affect the enzyme's stability and kinetics.
32782472	10	65	theme	deficient	1864:1872	arg1	enzyme					1874:1879	the triple deficient enzyme	1853:1879	the triple deficient enzyme	1853:1879	Thus, site density (number of sites per gram cellulose) was 30-60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme.
32782472	2	66	theme	many	312:315	arg1	years					317:321	many years	312:321	many years	312:321	For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases.
32782472	1	67	theme	hydrolase	194:202	arg1	family					204:209	glycoside hydrolase family 7	184:211	glycoside hydrolase family 7	184:211	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	6	68	dep	mutants	1146:1152	arg1	TrCel7A					1154:1160	TrCel7A	1154:1160	TrCel7A	1154:1160	Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q ).
32782472	6	68	dep	mutants	1146:1152	arg1	N384Q					1178:1182	N384Q	1178:1182	N384Q	1178:1182	Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q ).
32782472	13	69	theme	TrCel7A	2295:2301	arg1	density					2284:2290	attack site density	2272:2290	attack site density of TrCel7A	2272:2301	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	12	70	link	N-linked	2126:2133	arg1	glycans					2135:2141	N-linked glycans	2126:2141	N-linked glycans	2126:2141	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	0	71	theme	crystalline	127:137	arg1	cellulose					139:147	crystalline cellulose	127:147	crystalline cellulose	127:147	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	13	72	theme	steric	2317:2322	arg1	hindrance					2324:2332	steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation	2317:2456	hindrance	2324:2332	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	5	73	theme	expression	853:862	arg1	hosts					864:868	Two expression hosts	849:868	Two expression hosts	849:868	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	73	theme	expression	853:862	arg1	oryzae					883:888	Aspergillus oryzae	871:888	Aspergillus oryzae	871:888	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	73	theme	expression	853:862	arg1	reesei					906:911	Trichoderma reesei	894:911	Trichoderma reesei	894:911	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	13	74	dep	enzyme	2366:2371	arg1	the					2362:2364	the	2362:2364	the	2362:2364	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	5	75	dep	mutants	1030:1036	arg1	ΔN-glyc					1078:1084	ΔN-glyc	1078:1084	ΔN-glyc	1078:1084	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	75	dep	mutants	1030:1036	arg1	ΔN-glyc					1066:1072	ΔN-glyc	1066:1072	ΔN-glyc	1066:1072	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	75	dep	mutants	1030:1036	arg1	mutants					1030:1036	the triple N-glycosylation site deficient mutants	988:1036	the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc )	988:1086	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	75	dep	mutants	1030:1036	arg1	N384Q					1059:1063	N384Q	1059:1063	N384Q	1059:1063	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	75	dep	mutants	1030:1036	arg1	N270Q					1052:1056	N270Q	1052:1056	N270Q	1052:1056	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	11	76	theme	dynamic	1892:1898	arg1	simulation					1900:1909	Molecular dynamic simulation	1882:1909	Molecular dynamic simulation of the N-glycan mutants TrCel7A	1882:1941	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	13	77	theme	attack	2272:2277	arg1	density					2284:2290	attack site density	2272:2290	attack site density of TrCel7A	2272:2301	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	0	78	from	reesei	72:77	arg1	Removal					0:6	Removal	0:6	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei	0:77	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	11	79	theme	N-glycan	1918:1925	arg1	TrCel7A					1935:1941	TrCel7A	1935:1941	TrCel7A	1935:1941	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	11	79	theme	N-glycan	1918:1925	arg1	mutants					1927:1933	the N-glycan mutants	1914:1933	the N-glycan mutants TrCel7A	1914:1941	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	13	80	theme	extended	2226:2233	arg1	structures					2235:2244	extended structures	2226:2244	extended structures	2226:2244	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	13	81	theme	optimal	2437:2443	arg1	conformation					2445:2456	optimal conformation	2437:2456	optimal conformation	2437:2456	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	8	82	theme	deficient	1478:1486	arg1	mutants					1488:1494	the triple deficient mutants	1467:1494	the triple deficient mutants	1467:1494	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	11	83	from	N384	2055:2058	arg1	glycans					2027:2033	glycans	2027:2033	glycans at position N45 and N384	2027:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	11	83	from	N384	2055:2058	arg1	removal					2016:2022	removal	2016:2022	removal of glycans at position N45 and N384	2016:2058	Molecular dynamic simulation of the N-glycan mutants TrCel7A revealed higher number of contacts between CD and cellulose crystal upon removal of glycans at position N45 and N384.
32782472	10	84	theme	single	1778:1783	arg1	variants					1795:1802	the single deficient variants	1774:1802	the single deficient variants compared to the WT	1774:1821	Thus, site density (number of sites per gram cellulose) was 30-60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme.
32782472	5	85	theme	wild-types	952:961	arg1	TrCel7A					963:969	wild-types TrCel7A	952:969	wild-types TrCel7A (WT and WT )	952:982	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	7	86	theme	substrate-	1256:1265	arg1	conditions					1289:1298	both substrate- and enzyme-saturating conditions	1251:1298	both substrate- and enzyme-saturating conditions using different cellulosic substrates	1251:1336	The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates.
32782472	1	87	theme	BACKGROUND	150:159	arg1	Cellobiohydrolase					161:177	BACKGROUND Cellobiohydrolase	150:177	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7	150:211	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	1	87	theme	BACKGROUND	150:159	arg1	component					224:232	a major component	216:232	a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation	216:305	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	0	88	from	glycans	20:26	arg1	Cel7A					49:53	cellobiohydrolase Cel7A	31:53	cellobiohydrolase Cel7A	31:53	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	10	89	dep	density	1707:1713	arg1	number					1716:1721	number	1716:1721	number of sites per gram cellulose	1716:1749	Thus, site density (number of sites per gram cellulose) was 30-60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme.
32782472	0	90	theme	higher	87:92	arg1	activity					94:101	higher activity	87:101	higher activity	87:101	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	1	91	from	family	204:209	arg1	Cellobiohydrolase					161:177	BACKGROUND Cellobiohydrolase	150:177	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7	150:211	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	1	91	from	family	204:209	arg1	component					224:232	a major component	216:232	a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation	216:305	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	13	92	theme	N-glycans	2211:2219	arg1	presence					2199:2206	The presence	2195:2206	The presence of N-glycans with extended structures	2195:2244	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	8	93	theme	Michaelis	1343:1351	arg1	lowered					1396:1402	lowered	1396:1402	lowered	1396:1402	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	8	93	theme	Michaelis	1343:1351	arg1	K					1363:1363	K	1363:1363	K	1363:1363	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	8	93	theme	Michaelis	1343:1351	arg1	constant					1353:1360	The Michaelis constant	1339:1360	The Michaelis constant (K )	1339:1365	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	13	94	with	presence	2199:2206	arg1	structures					2235:2244	extended structures	2226:2244	extended structures	2226:2244	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	13	95	theme	cellulose	2381:2389	arg1	surface					2391:2397	the cellulose surface	2377:2397	the cellulose surface	2377:2397	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	2	96	theme	Trichoderma	324:334	arg1	reesei					336:341	Trichoderma reesei Cel7A (TrCel7A)	324:357	Trichoderma reesei Cel7A (TrCel7A)	324:357	For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases.
32782472	2	96	theme	Trichoderma	324:334	arg1	model					375:379	a model	373:379	a model to understand structure-function relationships of processive cellobiohydrolases	373:459	For many years, Trichoderma reesei Cel7A (TrCel7A) has served as a model to understand structure-function relationships of processive cellobiohydrolases.
32782472	12	97	theme	substrate	2170:2178	arg1	accessibility					2180:2192	substrate accessibility	2170:2192	substrate accessibility	2170:2192	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	5	98	dep	TrCel7A	963:969	arg1	WT					979:980	WT	979:980	WT	979:980	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	98	dep	TrCel7A	963:969	arg1	WT					972:973	WT	972:973	WT	972:973	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	13	99	dep	hindrance	2324:2332	arg1	effect					2334:2339	effect	2334:2339	effect	2334:2339	The presence of N-glycans with extended structures increased K and decreased attack site density of TrCel7A likely due to steric hindrance effect and distance between the enzyme and the cellulose surface, preventing the enzyme from achieving optimal conformation.
32782472	9	100	from	sites	1612:1616	arg1	surface					1635:1641	the cellulose surface	1621:1641	the cellulose surface	1621:1641	The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates.
32782472	8	101	theme	value	1531:1535	arg1	half					1514:1517	half	1514:1517	half of the WTs' value on some substrates	1514:1554	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
32782472	6	102	gly	N-glycosylation	1115:1129	arg2	site					1131:1134	N-glycosylation site	1115:1134	N-glycosylation site	1115:1134	Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q ).
32782472	12	103	theme	glycans	2135:2141	arg1	removal					2115:2121	removal	2115:2121	removal of N-linked glycans	2115:2141	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	0	104	theme	glycans	20:26	arg1	Removal					0:6	Removal	0:6	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei	0:77	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	12	105	dep	CONCLUSIONS	2061:2071	arg1	changes					2085:2091	The kinetic changes	2073:2091	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans	2061:2141	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	7	106	theme	cellulosic	1316:1325	arg1	substrates					1327:1336	different cellulosic substrates	1306:1336	different cellulosic substrates	1306:1336	The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates.
32782472	4	107	theme	glycans	778:784	arg1	pattern					767:773	a complex pattern	757:773	a complex pattern	757:773	Depending on the fungal expression host, glycosylation can vary not only in glycoforms, but also in site occupancy, leading to a complex pattern of glycans, which can affect the enzyme's stability and kinetics.
32782472	10	108	theme	site	1702:1705	arg1	density					1707:1713	site density	1702:1713	site density (number of sites per gram cellulose)	1702:1750	Thus, site density (number of sites per gram cellulose) was 30-60% higher for the single deficient variants compared to the WT, and about twofold larger for the triple deficient enzyme.
32782472	0	109	theme	cellobiohydrolase	31:47	arg1	Cel7A					49:53	cellobiohydrolase Cel7A	31:53	cellobiohydrolase Cel7A	31:53	Removal of N-linked glycans in cellobiohydrolase Cel7A from Trichoderma reesei reveals higher activity and binding affinity on crystalline cellulose.
32782472	14	110	theme	enzyme	2501:2506	arg1	glycosylation					2508:2520	enzyme glycosylation	2501:2520	enzyme glycosylation	2501:2520	This knowledge could be applied to modify enzyme glycosylation to engineer enzyme with higher activity on the insoluble substrates.
32782472	5	111	gly	N-glycosylation	999:1013	arg2	ΔN-glyc					1066:1072	ΔN-glyc	1066:1072	ΔN-glyc	1066:1072	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	111	gly	N-glycosylation	999:1013	arg2	ΔN-glyc					1078:1084	ΔN-glyc	1078:1084	ΔN-glyc	1078:1084	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	111	gly	N-glycosylation	999:1013	arg2	mutants					1030:1036	the triple N-glycosylation site deficient mutants	988:1036	the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc )	988:1086	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	111	gly	N-glycosylation	999:1013	arg2	site					1015:1018	the triple N-glycosylation site deficient mutants	988:1036	the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc )	988:1086	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	3	112	theme	N-glycosylated	502:515	arg1	domain					527:532	an N-glycosylated catalytic domain	499:532	an N-glycosylated catalytic domain	499:532	The architecture of TrCel7A includes an N-glycosylated catalytic domain, which is connected to a carbohydrate-binding module through a flexible, O-glycosylated linker.
32782472	9	113	theme	enzyme	1576:1581	arg1	ability					1561:1567	The ability	1557:1567	The ability of the enzyme to combine productively with sites on the cellulose surface	1557:1641	The ability of the enzyme to combine productively with sites on the cellulose surface followed a similar pattern on all tested substrates.
32782472	7	114	theme	enzyme-saturating	1271:1287	arg1	conditions					1289:1298	both substrate- and enzyme-saturating conditions	1251:1298	both substrate- and enzyme-saturating conditions using different cellulosic substrates	1251:1336	The TrCel7A enzymes were studied by steady-state kinetics under both substrate- and enzyme-saturating conditions using different cellulosic substrates.
32782472	12	115	theme	TrCel7A	2096:2102	arg1	changes					2085:2091	The kinetic changes	2073:2091	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans	2061:2141	CONCLUSIONS The kinetic changes of TrCel7A imposed by removal of N-linked glycans reflected modifications of substrate accessibility.
32782472	5	116	theme	N-glycosylation	999:1013	arg1	ΔN-glyc					1078:1084	ΔN-glyc	1078:1084	ΔN-glyc	1078:1084	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	116	theme	N-glycosylation	999:1013	arg1	mutants					1030:1036	the triple N-glycosylation site deficient mutants	988:1036	the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc )	988:1086	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	116	theme	N-glycosylation	999:1013	arg1	ΔN-glyc					1066:1072	ΔN-glyc	1066:1072	ΔN-glyc	1066:1072	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	6	117	theme	N-glycosylation	1115:1129	arg1	site					1131:1134	N-glycosylation site	1115:1134	N-glycosylation site	1115:1134	Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q ).
32782472	6	118	theme	deficient	1136:1144	arg1	mutants					1146:1152	single N-glycosylation site deficient mutants	1108:1152	single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q )	1108:1184	Also, we expressed single N-glycosylation site deficient mutants TrCel7A (N45Q , N270Q , N384Q ).
32782472	1	119	theme	enzymatic	248:256	arg1	mixtures					258:265	commercial enzymatic mixtures	237:265	commercial enzymatic mixtures	237:265	BACKGROUND Cellobiohydrolase from glycoside hydrolase family 7 is a major component of commercial enzymatic mixtures for lignocellulosic biomass degradation.
32782472	5	120	theme	deficient	1020:1028	arg1	ΔN-glyc					1078:1084	ΔN-glyc	1078:1084	ΔN-glyc	1078:1084	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	120	theme	deficient	1020:1028	arg1	mutants					1030:1036	the triple N-glycosylation site deficient mutants	988:1036	the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc )	988:1086	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	5	120	theme	deficient	1020:1028	arg1	ΔN-glyc					1066:1072	ΔN-glyc	1066:1072	ΔN-glyc	1066:1072	RESULTS Two expression hosts, Aspergillus oryzae and Trichoderma reesei, were utilized to successfully express wild-types TrCel7A (WT and WT ) and the triple N-glycosylation site deficient mutants TrCel7A N45Q, N270Q, N384Q (ΔN-glyc and ΔN-glyc ).
32782472	8	121	theme	N-glycosylation	1434:1448	arg1	content					1450:1456	reduced N-glycosylation content	1426:1456	reduced N-glycosylation content	1426:1456	The Michaelis constant (K ) was consistently found to be lowered for the variants with reduced N-glycosylation content, and for the triple deficient mutants, it was less than half of the WTs' value on some substrates.
34893213	0	0	theme	part	101:104	arg1	Impact					70:75	Impact	70:75	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.	0:105	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.
34893213	5	1	theme	highest	747:753	arg1	ratio					771:775	the highest mannose/glucose ratio	743:775	the highest mannose/glucose ratio	743:775	MP-Com had the highest mannose/glucose ratio followed by MP-WT/MP-Mnn4, and MP-Mnn2 (13.5 > 5.6 ≈ 5.2 > 2.2).
34893213	6	2	theme	Rg	873:874	arg1	dependencies					857:868	The molar mass dependencies	842:868	The molar mass dependencies	842:868	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	0	3	theme	polysaccharide	86:99	arg1	part					101:104	their polysaccharide part	80:104	their polysaccharide part	80:104	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.
34893213	6	4	theme	[η	885:886	arg1	dependencies					857:868	The molar mass dependencies	842:868	The molar mass dependencies	842:868	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	2	5	theme	yeast	361:365	arg1	strain					367:372	a laboratory yeast strain	348:372	a laboratory yeast strain (WT)	348:377	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	5	theme	yeast	361:365	arg1	WT					375:376	WT	375:376	WT	375:376	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	6	6	theme	mass	852:855	arg1	dependencies					857:868	The molar mass dependencies	842:868	The molar mass dependencies	842:868	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	6	7	theme	related	1001:1007	arg1	mannoproteins					987:999	mannoproteins	987:999	mannoproteins related to their nature of highly branched copolymers with two branching levels	987:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	5	8	contain	had	739:741	arg2	ratio					771:775	the highest mannose/glucose ratio	743:775	the highest mannose/glucose ratio	743:775	MP-Com had the highest mannose/glucose ratio followed by MP-WT/MP-Mnn4, and MP-Mnn2 (13.5 > 5.6 ≈ 5.2 > 2.2).
34893213	5	8	contain	had	739:741	arg1	MP-Com					732:737	MP-Com	732:737	MP-Com	732:737	MP-Com had the highest mannose/glucose ratio followed by MP-WT/MP-Mnn4, and MP-Mnn2 (13.5 > 5.6 ≈ 5.2 > 2.2).
34893213	4	9	theme	Glycosyl-linkage	634:649	arg1	analyses					666:673	Glycosyl-linkage and net charge analyses	634:673	Glycosyl-linkage and net charge analyses	634:673	Glycosyl-linkage and net charge analyses confirmed the expected differences in mutant strain MPs.
34893213	6	10	theme	mannoproteins	987:999	arg1	properties					973:982	specific conformational properties	949:982	specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels	949:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	2	11	theme	laboratory	350:359	arg1	strain					367:372	a laboratory yeast strain	348:372	a laboratory yeast strain (WT)	348:377	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	11	theme	laboratory	350:359	arg1	WT					375:376	WT	375:376	WT	375:376	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	1	12	theme	structure-function	167:184	arg1	relationships					186:198	the structure-function relationships	163:198	the structure-function relationships of mannoproteins	163:215	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	2	13	theme	enological	494:503	arg1	strain					505:510	an enological strain	491:510	an enological strain (Com)	491:516	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	13	theme	enological	494:503	arg1	Com					513:515	Com	513:515	Com	513:515	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	7	14	theme	structural	1105:1114	arg1	differences					1116:1126	structural differences	1105:1126	structural differences between MP-Com, MP-WT/Mnn4, and MP Mnn2	1105:1166	It also clearly showed structural differences between MP-Com, MP-WT/Mnn4, and MP Mnn2, and differences between two populations within the four mannoproteins.
34893213	6	15	theme	molar	846:850	arg1	dependencies					857:868	The molar mass dependencies	842:868	The molar mass dependencies	842:868	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	0	16	theme	Structural	0:9	arg1	characteristics					11:25	Structural characteristics	0:25	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.	0:105	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.
34893213	5	17	theme	mannose/glucose	755:769	arg1	ratio					771:775	the highest mannose/glucose ratio	743:775	the highest mannose/glucose ratio	743:775	MP-Com had the highest mannose/glucose ratio followed by MP-WT/MP-Mnn4, and MP-Mnn2 (13.5 > 5.6 ≈ 5.2 > 2.2).
34893213	6	18	theme	Rh	877:878	arg1	dependencies					857:868	The molar mass dependencies	842:868	The molar mass dependencies	842:868	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	4	19	theme	net	655:657	arg1	charge					659:664	net charge	655:664	net charge	655:664	Glycosyl-linkage and net charge analyses confirmed the expected differences in mutant strain MPs.
34893213	2	20	theme	N-glycosylated	421:434	arg1	chains					436:441	unbranched N-glycosylated chains	410:441	unbranched N-glycosylated chains	410:441	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	4	21	theme	strain	720:725	arg1	MPs					727:729	mutant strain MPs	713:729	mutant strain MPs	713:729	Glycosyl-linkage and net charge analyses confirmed the expected differences in mutant strain MPs.
34893213	1	22	theme	mannoproteins	203:215	arg1	part					225:228	the part	221:228	the part played by their polysaccharide moiety	221:266	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	1	22	theme	mannoproteins	203:215	arg1	relationships					186:198	the structure-function relationships	163:198	the structure-function relationships of mannoproteins	163:215	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	0	23	theme	Saccharomyces	30:42	arg1	mannoproteins					55:67	Saccharomyces cerevisiae mannoproteins	30:67	Saccharomyces cerevisiae mannoproteins	30:67	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.
34893213	6	24	theme	conformational	958:971	arg1	properties					973:982	specific conformational properties	949:982	specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels	949:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	6	25	theme	specific	949:956	arg1	properties					973:982	specific conformational properties	949:982	specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels	949:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	3	26	theme	acid	616:619	arg1	composition					621:631	the same amino acid composition	601:631	the same amino acid composition	601:631	The protein moiety of the four MPs had the same amino acid composition.
34893213	0	27	theme	mannoproteins	55:67	arg1	characteristics					11:25	Structural characteristics	0:25	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.	0:105	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.
34893213	5	28	dep	had	739:741	arg1	followed					777:784	followed	777:784	followed by MP-WT/MP-Mnn4, and MP-Mnn2 (13.5 > 5.6 ≈ 5.2 > 2.2)	777:839	MP-Com had the highest mannose/glucose ratio followed by MP-WT/MP-Mnn4, and MP-Mnn2 (13.5 > 5.6 ≈ 5.2 > 2.2).
34893213	6	29	theme	copolymers	1044:1053	arg1	nature					1018:1023	their nature	1012:1023	their nature of highly branched copolymers with two branching levels	1012:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	2	30	dep	mutants	391:397	arg1	Mnn4					447:450	Mnn4	447:450	Mnn4	447:450	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	30	dep	mutants	391:397	arg1	mutants					391:397	its mutants	387:397	its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation)	387:484	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	30	dep	mutants	391:397	arg1	Mnn2					400:403	Mnn2	400:403	Mnn2	400:403	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	6	31	theme	branching	1064:1072	arg1	levels					1074:1079	two branching levels	1060:1079	two branching levels	1060:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	2	32	theme	mutants	391:397	arg1	two					380:382	two	380:382	two	380:382	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	32	theme	mutants	391:397	arg1	mutants					391:397	its mutants	387:397	its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation)	387:484	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	32	theme	mutants	391:397	arg1	Mnn4					447:450	Mnn4	447:450	Mnn4	447:450	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	2	32	theme	mutants	391:397	arg1	Mnn2					400:403	Mnn2	400:403	Mnn2	400:403	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	0	33	theme	cerevisiae	44:53	arg1	mannoproteins					55:67	Saccharomyces cerevisiae mannoproteins	30:67	Saccharomyces cerevisiae mannoproteins	30:67	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.
34893213	1	34	contain	have	118:121	arg1	they					113:116	they	113:116	they	113:116	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	1	34	contain	have	118:121	arg2	properties					128:137	many properties	123:137	many properties of interest	123:149	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	7	35	theme	MP	1160:1161	arg1	Mnn2					1163:1166	MP Mnn2	1160:1166	MP Mnn2	1160:1166	It also clearly showed structural differences between MP-Com, MP-WT/Mnn4, and MP Mnn2, and differences between two populations within the four mannoproteins.
34893213	3	36	theme	same	605:608	arg1	composition					621:631	the same amino acid composition	601:631	the same amino acid composition	601:631	The protein moiety of the four MPs had the same amino acid composition.
34893213	2	37	theme	unbranched	410:419	arg1	chains					436:441	unbranched N-glycosylated chains	410:441	unbranched N-glycosylated chains	410:441	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	6	38	theme	branched	1035:1042	arg1	copolymers					1044:1053	highly branched copolymers	1028:1053	highly branched copolymers with two branching levels	1028:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	3	39	theme	amino	610:614	arg1	composition					621:631	the same amino acid composition	601:631	the same amino acid composition	601:631	The protein moiety of the four MPs had the same amino acid composition.
34893213	3	40	theme	protein	566:572	arg1	moiety					574:579	The protein moiety	562:579	The protein moiety of the four MPs	562:595	The protein moiety of the four MPs had the same amino acid composition.
34893213	1	41	theme	many	123:126	arg1	properties					128:137	many properties	123:137	many properties of interest	123:149	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	6	42	with	copolymers	1044:1053	arg1	levels					1074:1079	two branching levels	1060:1079	two branching levels	1060:1079	The molar mass dependencies of Rg, Rh, and [η], determined through HPSEC-MALLS-QELS-Viscosimetry, revealed specific conformational properties of mannoproteins related to their nature of highly branched copolymers with two branching levels.
34893213	4	43	theme	expected	689:696	arg1	differences					698:708	the expected differences	685:708	the expected differences in mutant strain MPs	685:729	Glycosyl-linkage and net charge analyses confirmed the expected differences in mutant strain MPs.
34893213	2	44	gly	N-glycosylated	421:434	arg1	chains					436:441	unbranched N-glycosylated chains	410:441	unbranched N-glycosylated chains	410:441	Mannoproteins (MP) extracted with β-glucanase from a laboratory yeast strain (WT), two of its mutants (Mnn2 with unbranched N-glycosylated chains and Mnn4 without mannosyl-phosphorylation), and an enological strain (Com) were purified and thoroughly characterized.
34893213	4	45	theme	mutant	713:718	arg1	MPs					727:729	mutant strain MPs	713:729	mutant strain MPs	713:729	Glycosyl-linkage and net charge analyses confirmed the expected differences in mutant strain MPs.
34893213	1	46	theme	interest	142:149	arg1	properties					128:137	many properties	123:137	many properties of interest	123:149	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	4	47	from	differences	698:708	arg1	MPs					727:729	mutant strain MPs	713:729	mutant strain MPs	713:729	Glycosyl-linkage and net charge analyses confirmed the expected differences in mutant strain MPs.
34893213	0	48	dep	characteristics	11:25	arg1	Impact					70:75	Impact	70:75	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.	0:105	Structural characteristics of Saccharomyces cerevisiae mannoproteins: Impact of their polysaccharide part.
34893213	1	49	theme	polysaccharide	246:259	arg1	moiety					261:266	their polysaccharide moiety	240:266	their polysaccharide moiety	240:266	While they have many properties of interest in enology, the structure-function relationships of mannoproteins and the part played by their polysaccharide moiety are not yet well understood.
34893213	3	50	theme	MPs	593:595	arg1	moiety					574:579	The protein moiety	562:579	The protein moiety of the four MPs	562:595	The protein moiety of the four MPs had the same amino acid composition.
34893213	4	51	theme	charge	659:664	arg1	analyses					666:673	Glycosyl-linkage and net charge analyses	634:673	Glycosyl-linkage and net charge analyses	634:673	Glycosyl-linkage and net charge analyses confirmed the expected differences in mutant strain MPs.
34893213	3	52	contain	had	597:599	arg2	composition					621:631	the same amino acid composition	601:631	the same amino acid composition	601:631	The protein moiety of the four MPs had the same amino acid composition.
34893213	3	52	contain	had	597:599	arg1	moiety					574:579	The protein moiety	562:579	The protein moiety of the four MPs	562:595	The protein moiety of the four MPs had the same amino acid composition.
32898699	2	0	from	expands	204:210	arg1	topic					220:224	this topic	215:224	this topic	215:224	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	10	1	dep	cohort	1440:1445	arg1	either					1409:1414	either	1409:1414	either	1409:1414	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	11	2	theme	biochemical	1457:1467	arg1	point					1469:1473	the biochemical point	1453:1473	the biochemical point of view	1453:1481	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	6	3	theme	desorption/ionization	853:873	arg1	MALDI-MS					894:901	MALDI-MS	894:901	MALDI-MS	894:901	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	6	3	theme	desorption/ionization	853:873	arg1	spectrometry					880:891	matrix-assisted laser desorption/ionization mass spectrometry	831:891	matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:902	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	16	4	gly	N-glycosylation	2308:2322	arg1	proteins					2327:2334	proteins	2327:2334	proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2327:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	6	5	theme	matrix-assisted	831:845	arg1	MALDI-MS					894:901	MALDI-MS	894:901	MALDI-MS	894:901	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	6	5	theme	matrix-assisted	831:845	arg1	spectrometry					880:891	matrix-assisted laser desorption/ionization mass spectrometry	831:891	matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:902	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	14	6	theme	major	2000:2004	arg1	impediment					2006:2015	a major impediment	1998:2015	a major impediment to a successful treatment of patients with advanced ovarian cancer	1998:2082	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	12	7	theme	cancer	1796:1801	arg1	patients					1803:1810	ovarian cancer patients	1788:1810	ovarian cancer patients	1788:1810	Among them, six tissue N-glycans could be considered potential markers connected with a resistance to chemotherapy in ovarian cancer patients.
32898699	9	8	theme	validation	1238:1247	arg1	cohort					1249:1254	the validation cohort	1234:1254	the validation cohort	1234:1254	One of these glycans was detected as differentially abundant in sera of the validation cohort.
32898699	2	9	theme	stage	322:326	arg1	cancer					361:366	advanced stage, high-grade non-mucinous ovarian cancer	313:366	cancer	361:366	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	13	10	theme	resistance	1839:1848	arg1	prediction					1817:1826	The prediction	1813:1826	The prediction of primary resistance to standard chemotherapy	1813:1873	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	13	11	theme	patients	1901:1908	arg1	patients					1901:1908	patients	1901:1908	patients suitable for alternative treatment strategies	1901:1954	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	13	11	theme	patients	1901:1908	arg1	group					1892:1896	the group	1888:1896	the group of patients suitable for alternative treatment strategies	1888:1954	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	1	12	gly	glycosylation	133:145	arg1	connection					150:159	connection	150:159	connection with malignancy	150:175	A number of studies have reported aberrant glycosylation in connection with malignancy.
32898699	5	13	theme	preoperative	708:719	arg1	samples					727:733	preoperative serum samples	708:733	preoperative serum samples	708:733	In the validation cohort, preoperative serum samples were also available.
32898699	1	14	theme	aberrant	124:131	arg1	glycosylation					133:145	aberrant glycosylation	124:145	aberrant glycosylation	124:145	A number of studies have reported aberrant glycosylation in connection with malignancy.
32898699	12	15	from	resistance	1758:1767	arg1	patients					1803:1810	ovarian cancer patients	1788:1810	ovarian cancer patients	1788:1810	Among them, six tissue N-glycans could be considered potential markers connected with a resistance to chemotherapy in ovarian cancer patients.
32898699	10	16	theme	validation	1429:1438	arg1	cohort					1440:1445	either the basic or validation cohort	1409:1445	cohort	1440:1445	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	12	17	theme	ovarian	1788:1794	arg1	patients					1803:1810	ovarian cancer patients	1788:1810	ovarian cancer patients	1788:1810	Among them, six tissue N-glycans could be considered potential markers connected with a resistance to chemotherapy in ovarian cancer patients.
32898699	16	18	theme	platinum/taxane-based	2422:2442	arg1	chemotherapy					2444:2455	platinum/taxane-based chemotherapy	2422:2455	platinum/taxane-based chemotherapy	2422:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	0	19	theme	ovarian	74:80	arg1	cancer					82:87	ovarian cancer	74:87	ovarian cancer	74:87	N-Glycome changes reflecting resistance to platinum-based chemotherapy in ovarian cancer.
32898699	14	20	with	patients	2046:2053	arg1	cancer					2077:2082	advanced ovarian cancer	2060:2082	advanced ovarian cancer	2060:2082	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	13	21	theme	standard	1853:1860	arg1	chemotherapy					1862:1873	standard chemotherapy	1853:1873	standard chemotherapy	1853:1873	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	11	22	theme	terminal	1573:1580	arg1	residue					1590:1596	bisecting (terminal) GlcNAc residue	1562:1596	bisecting (terminal) GlcNAc residue	1562:1596	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	7	23	theme	spectral	992:999	arg1	signals					1001:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	10	24	located	found	1344:1348	arg1	cases					1357:1361	the cases	1353:1361	the cases without postoperative macroscopic residues in either the basic or validation cohort	1353:1445	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	10	24	located	found	1344:1348	arg2	differences					1286:1296	No statistically significant differences	1257:1296	No statistically significant differences in intensities due to the same N-glycans	1257:1337	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	11	25	theme	bisecting	1562:1570	arg1	residue					1590:1596	bisecting (terminal) GlcNAc residue	1562:1596	bisecting (terminal) GlcNAc residue	1562:1596	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	0	26	from	chemotherapy	58:69	arg1	cancer					82:87	ovarian cancer	74:87	ovarian cancer	74:87	N-Glycome changes reflecting resistance to platinum-based chemotherapy in ovarian cancer.
32898699	10	27	theme	same	1324:1327	arg1	N-glycans					1329:1337	the same N-glycans	1320:1337	the same N-glycans	1320:1337	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	3	28	theme	cancer	444:449	arg1	patients					451:458	83 ovarian cancer patients	433:458	83 ovarian cancer patients	433:458	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	0	29	theme	N-Glycome	0:8	arg1	changes					10:16	N-Glycome changes	0:16	N-Glycome changes	0:16	N-Glycome changes reflecting resistance to platinum-based chemotherapy in ovarian cancer.
32898699	8	30	theme	independent	1085:1095	arg1	cohorts					1097:1103	both independent cohorts	1080:1103	both independent cohorts	1080:1103	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	16	31	from	samples	2356:2362	arg1	N-glycosylation					2308:2322	N-glycosylation	2308:2322	N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2308:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	12	32	theme	tissue	1686:1691	arg1	N-glycans					1693:1701	six tissue N-glycans	1682:1701	six tissue N-glycans	1682:1701	Among them, six tissue N-glycans could be considered potential markers connected with a resistance to chemotherapy in ovarian cancer patients.
32898699	15	33	theme	related	2111:2117	arg1	measurements					2098:2109	The glycomic measurements	2085:2109	The glycomic measurements related to cancer	2085:2127	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	10	34	theme	basic	1420:1424	arg1	cohort					1440:1445	either the basic or validation cohort	1409:1445	cohort	1440:1445	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	13	35	theme	suitable	1910:1917	arg1	patients					1901:1908	patients	1901:1908	patients suitable for alternative treatment strategies	1901:1954	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	14	36	theme	ovarian	2069:2075	arg1	cancer					2077:2082	advanced ovarian cancer	2060:2082	advanced ovarian cancer	2060:2082	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	15	37	theme	potential	2205:2213	arg1	indicators					2241:2250	potential diagnostic and prognostic indicators	2205:2250	potential diagnostic and prognostic indicators	2205:2250	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	10	38	from	residues	1397:1404	arg1	cohort					1440:1445	either the basic or validation cohort	1409:1445	cohort	1440:1445	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	4	39	theme	tumor	592:596	arg1	residue					598:604	postoperative tumor residue	578:604	postoperative tumor residue	578:604	Both groups involved either cases with/without postoperative tumor residue or the cases determined either resistant or sensitive to this chemotherapy.
32898699	15	40	theme	glycomic	2089:2096	arg1	measurements					2098:2109	The glycomic measurements	2085:2109	The glycomic measurements related to cancer	2085:2127	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	13	41	theme	alternative	1923:1933	arg1	strategies					1945:1954	alternative treatment strategies	1923:1954	alternative treatment strategies	1923:1954	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	3	42	used	used	410:413	arg2	We					407:408	We	407:408	We	407:408	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	15	43	theme	prognostic	2230:2239	arg1	indicators					2241:2250	potential diagnostic and prognostic indicators	2205:2250	potential diagnostic and prognostic indicators	2205:2250	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	10	44	theme	postoperative	1371:1383	arg1	residues					1397:1404	postoperative macroscopic residues	1371:1404	postoperative macroscopic residues in either the basic or validation cohort	1371:1445	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	2	45	theme	cancer	361:366	arg1	resistance					299:308	the resistance	295:308	the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy	295:404	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	15	46	theme	diagnostic	2215:2224	arg1	indicators					2241:2250	potential diagnostic and prognostic indicators	2205:2250	potential diagnostic and prognostic indicators	2205:2250	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	2	47	theme	non-mucinous	340:351	arg1	cancer					361:366	advanced stage, high-grade non-mucinous ovarian cancer	313:366	cancer	361:366	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	8	48	theme	cancer	1146:1151	arg1	residue					1153:1159	a postoperative cancer residue	1130:1159	a postoperative cancer residue	1130:1159	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	11	49	theme	fucose	1653:1658	arg1	residues					1660:1667	fucose residues	1653:1667	fucose residues	1653:1667	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	15	50	theme	key	2188:2190	arg1	molecules					2192:2200	the key molecules	2184:2200	the key molecules as potential diagnostic and prognostic indicators	2184:2250	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	15	51	from	popular	2155:2161	arg1	identification					2166:2179	identification	2166:2179	identification of the key molecules as potential diagnostic and prognostic indicators	2166:2250	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	2	52	theme	platinum/taxane	371:385	arg1	chemotherapy					393:404	platinum/taxane based chemotherapy	371:404	platinum/taxane based chemotherapy	371:404	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	5	53	from	available	745:753	arg1	cohort					700:705	the validation cohort	685:705	the validation cohort	685:705	In the validation cohort, preoperative serum samples were also available.
32898699	15	54	from	identification	2166:2179	arg1	popular					2155:2161	popular	2155:2161	popular	2155:2161	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	5	55	theme	validation	689:698	arg1	cohort					700:705	the validation cohort	685:705	the validation cohort	685:705	In the validation cohort, preoperative serum samples were also available.
32898699	6	56	theme	mass	875:878	arg1	MALDI-MS					894:901	MALDI-MS	894:901	MALDI-MS	894:901	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	6	56	theme	mass	875:878	arg1	spectrometry					880:891	matrix-assisted laser desorption/ionization mass spectrometry	831:891	matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:902	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	7	57	theme	consecutive	931:941	arg1	detection					943:951	a consecutive detection	929:951	a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals	929:1007	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	8	58	theme	these	1019:1023	arg1	these					1019:1023	these	1019:1023	these	1019:1023	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	8	58	theme	these	1019:1023	arg1	Eight					1010:1014	Eight	1010:1014	Eight	1010:1014	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	6	59	theme	laser	847:851	arg1	MALDI-MS					894:901	MALDI-MS	894:901	MALDI-MS	894:901	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	6	59	theme	laser	847:851	arg1	spectrometry					880:891	matrix-assisted laser desorption/ionization mass spectrometry	831:891	matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)	831:902	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	11	60	theme	sialic	1634:1639	arg1	acid					1641:1644	sialic acid	1634:1644	sialic acid	1634:1644	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	7	61	theme	MS	909:910	arg1	analysis					912:919	The MS analysis	905:919	The MS analysis	905:919	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	8	62	from	tissues	1069:1075	arg1	abundant					1057:1064	abundant	1057:1064	abundant	1057:1064	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	10	63	from	differences	1286:1296	arg1	intensities					1301:1311	intensities	1301:1311	intensities due to the same N-glycans	1301:1337	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	13	64	theme	primary	1831:1837	arg1	resistance					1839:1848	primary resistance	1831:1848	primary resistance to standard chemotherapy	1831:1873	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	11	65	theme	tetra-antennary	1602:1616	arg1	structures					1618:1627	tetra-antennary structures	1602:1627	tetra-antennary structures	1602:1627	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	9	66	theme	cohort	1249:1254	arg1	sera					1226:1229	sera	1226:1229	sera of the validation cohort	1226:1254	One of these glycans was detected as differentially abundant in sera of the validation cohort.
32898699	2	67	theme	advanced	313:320	arg1	cancer					361:366	advanced stage, high-grade non-mucinous ovarian cancer	313:366	cancer	361:366	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	6	68	attach	released	766:773	arg2	N-glycans					756:764	N-glycans	756:764	N-glycans released from tumors and sera	756:794	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	6	68	attach	released	766:773	arg1	tumors					780:785	tumors	780:785	tumors	780:785	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	6	68	attach	released	766:773	arg1	sera					791:794	sera	791:794	sera	791:794	N-glycans released from tumors and sera were permethylated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
32898699	8	69	from	abundant	1057:1064	arg1	cases					1119:1123	the cases	1115:1123	the cases with a postoperative cancer residue	1115:1159	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	8	69	from	abundant	1057:1064	arg1	tissues					1069:1075	tissues	1069:1075	tissues of both independent cohorts including the cases with a postoperative cancer residue	1069:1159	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	16	70	from	N-glycosylation	2308:2322	arg1	tissue					2339:2344	tissue	2339:2344	tissue	2339:2344	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	16	70	from	N-glycosylation	2308:2322	arg1	identification					2275:2288	identification	2275:2288	identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2275:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	16	70	from	N-glycosylation	2308:2322	arg1	samples					2356:2362	serum samples	2350:2362	serum samples	2350:2362	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	2	71	theme	N-glycans	253:261	arg1	examination					238:248	the examination	234:248	the examination	234:248	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	14	72	theme	Drug	1971:1974	arg1	resistance					1976:1985	SIGNIFICANCE: Drug resistance	1957:1985	SIGNIFICANCE: Drug resistance	1957:1985	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	16	73	from	differences	2293:2303	arg1	N-glycosylation					2308:2322	N-glycosylation	2308:2322	N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2308:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	14	74	theme	SIGNIFICANCE	1957:1968	arg1	resistance					1976:1985	SIGNIFICANCE: Drug resistance	1957:1985	SIGNIFICANCE: Drug resistance	1957:1985	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	10	75	theme	significant	1274:1284	arg1	differences					1286:1296	No statistically significant differences	1257:1296	No statistically significant differences in intensities due to the same N-glycans	1257:1337	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	5	76	theme	serum	721:725	arg1	samples					727:733	preoperative serum samples	708:733	preoperative serum samples	708:733	In the validation cohort, preoperative serum samples were also available.
32898699	16	77	from	tissue	2339:2344	arg1	N-glycosylation					2308:2322	N-glycosylation	2308:2322	N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2308:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	17	78	theme	detection	2462:2470	arg1	important					2511:2519	important	2511:2519	important	2511:2519	The detection sensitivity to chemotherapy is vitally important for these patients.
32898699	17	78	theme	detection	2462:2470	arg1	sensitivity					2472:2482	The detection sensitivity	2458:2482	The detection sensitivity to chemotherapy	2458:2498	The detection sensitivity to chemotherapy is vitally important for these patients.
32898699	16	79	from	proteins	2327:2334	arg1	tissue					2339:2344	tissue	2339:2344	tissue	2339:2344	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	16	79	from	proteins	2327:2334	arg1	samples					2356:2362	serum samples	2350:2362	serum samples	2350:2362	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	16	79	from	proteins	2327:2334	arg1	individuals					2373:2383	the individuals	2369:2383	the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2369:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	9	80	from	sera	1226:1229	arg1	abundant					1214:1221	abundant	1214:1221	abundant	1214:1221	One of these glycans was detected as differentially abundant in sera of the validation cohort.
32898699	11	81	theme	GlcNAc	1583:1588	arg1	residue					1590:1596	bisecting (terminal) GlcNAc residue	1562:1596	bisecting (terminal) GlcNAc residue	1562:1596	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	9	82	from	abundant	1214:1221	arg1	sera					1226:1229	sera	1226:1229	sera of the validation cohort	1226:1254	One of these glycans was detected as differentially abundant in sera of the validation cohort.
32898699	14	83	theme	successful	2022:2031	arg1	treatment					2033:2041	a successful treatment	2020:2041	a successful treatment of patients with advanced ovarian cancer	2020:2082	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	1	84	with	connection	150:159	arg1	malignancy					166:175	malignancy	166:175	malignancy	166:175	A number of studies have reported aberrant glycosylation in connection with malignancy.
32898699	7	85	theme	signals	1001:1007	arg1	detection					943:951	a consecutive detection	929:951	a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals	929:1007	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	3	86	dep	cohorts	499:505	arg1	basic					508:512	basic	508:512	basic	508:512	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	3	86	dep	cohorts	499:505	arg1	validation					518:527	validation	518:527	validation	518:527	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	16	87	from	identification	2275:2288	arg1	N-glycosylation					2308:2322	N-glycosylation	2308:2322	N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2308:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	11	88	theme	view	1478:1481	arg1	point					1469:1473	the biochemical point	1453:1473	the biochemical point of view	1453:1481	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	16	89	theme	proteins	2327:2334	arg1	N-glycosylation					2308:2322	N-glycosylation	2308:2322	N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2308:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	13	90	theme	treatment	1935:1943	arg1	strategies					1945:1954	alternative treatment strategies	1923:1954	alternative treatment strategies	1923:1954	The prediction of primary resistance to standard chemotherapy may identify the group of patients suitable for alternative treatment strategies.
32898699	7	91	theme	N-glycan	983:990	arg1	signals					1001:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	8	92	theme	cohorts	1097:1103	arg1	cases					1119:1123	the cases	1115:1123	the cases with a postoperative cancer residue	1115:1159	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	8	92	theme	cohorts	1097:1103	arg1	tissues					1069:1075	tissues	1069:1075	tissues of both independent cohorts including the cases with a postoperative cancer residue	1069:1159	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	7	93	theme	serum	976:980	arg1	signals					1001:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	12	94	theme	potential	1723:1731	arg1	markers					1733:1739	potential markers	1723:1739	potential markers connected with a resistance to chemotherapy in ovarian cancer patients	1723:1810	Among them, six tissue N-glycans could be considered potential markers connected with a resistance to chemotherapy in ovarian cancer patients.
32898699	3	95	theme	tissue	415:420	arg1	samples					422:428	tissue samples	415:428	tissue samples	415:428	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	4	96	theme	postoperative	578:590	arg1	residue					598:604	postoperative tumor residue	578:604	postoperative tumor residue	578:604	Both groups involved either cases with/without postoperative tumor residue or the cases determined either resistant or sensitive to this chemotherapy.
32898699	11	97	theme	significant	1502:1512	arg1	N-glycans					1514:1522	the statistically significant N-glycans	1484:1522	the statistically significant N-glycans	1484:1522	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	3	98	theme	patients	451:458	arg1	samples					422:428	tissue samples	415:428	tissue samples	415:428	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	7	99	theme	63	972:973	arg1	signals					1001:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	1	100	theme	studies	102:108	arg1	number					92:97	A number	90:97	A number of studies	90:108	A number of studies have reported aberrant glycosylation in connection with malignancy.
32898699	3	101	theme	independent	487:497	arg1	cohorts					499:505	two independent cohorts	483:505	two independent cohorts (basic and validation)	483:528	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	0	102	theme	platinum-based	43:56	arg1	chemotherapy					58:69	platinum-based chemotherapy	43:69	platinum-based chemotherapy in ovarian cancer	43:87	N-Glycome changes reflecting resistance to platinum-based chemotherapy in ovarian cancer.
32898699	16	103	theme	serum	2350:2354	arg1	samples					2356:2362	serum samples	2350:2362	serum samples	2350:2362	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	11	104	contain	carrying	1553:1560	arg2	structures					1618:1627	tetra-antennary structures	1602:1627	tetra-antennary structures	1602:1627	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	11	104	contain	carrying	1553:1560	arg1	structures					1542:1551	the structures	1538:1551	the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues	1538:1667	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	11	104	contain	carrying	1553:1560	arg2	residue					1590:1596	bisecting (terminal) GlcNAc residue	1562:1596	bisecting (terminal) GlcNAc residue	1562:1596	From the biochemical point of view, the statistically significant N-glycans correspond to the structures carrying bisecting (terminal) GlcNAc residue and tetra-antennary structures with sialic acid and/or fucose residues.
32898699	14	105	theme	advanced	2060:2067	arg1	cancer					2077:2082	advanced ovarian cancer	2060:2082	advanced ovarian cancer	2060:2082	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	3	106	theme	ovarian	436:442	arg1	patients					451:458	83 ovarian cancer patients	433:458	83 ovarian cancer patients	433:458	We used tissue samples of 83 ovarian cancer patients, randomly divided into two independent cohorts (basic and validation).
32898699	10	107	theme	macroscopic	1385:1395	arg1	residues					1397:1404	postoperative macroscopic residues	1371:1404	postoperative macroscopic residues in either the basic or validation cohort	1371:1445	No statistically significant differences in intensities due to the same N-glycans were found in the cases without postoperative macroscopic residues in either the basic or validation cohort.
32898699	5	108	from	cohort	700:705	arg1	available					745:753	available	745:753	available	745:753	In the validation cohort, preoperative serum samples were also available.
32898699	8	109	theme	postoperative	1132:1144	arg1	residue					1153:1159	a postoperative cancer residue	1130:1159	a postoperative cancer residue	1130:1159	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	14	110	theme	patients	2046:2053	arg1	treatment					2033:2041	a successful treatment	2020:2041	a successful treatment of patients with advanced ovarian cancer	2020:2082	SIGNIFICANCE: Drug resistance has become a major impediment to a successful treatment of patients with advanced ovarian cancer.
32898699	2	111	theme	ovarian	353:359	arg1	cancer					361:366	advanced stage, high-grade non-mucinous ovarian cancer	313:366	cancer	361:366	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	16	112	from	individuals	2373:2383	arg1	tissue					2339:2344	tissue	2339:2344	tissue	2339:2344	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	16	112	from	individuals	2373:2383	arg1	samples					2356:2362	serum samples	2350:2362	serum samples	2350:2362	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	16	112	from	individuals	2373:2383	arg1	proteins					2327:2334	proteins	2327:2334	proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2327:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	15	113	theme	molecules	2192:2200	arg1	identification					2166:2179	identification	2166:2179	identification of the key molecules as potential diagnostic and prognostic indicators	2166:2250	The glycomic measurements related to cancer are becoming increasingly popular in identification of the key molecules as potential diagnostic and prognostic indicators.
32898699	8	114	with	cases	1119:1123	arg1	residue					1153:1159	a postoperative cancer residue	1130:1159	a postoperative cancer residue	1130:1159	Eight of these were found to be differentially abundant in tissues of both independent cohorts including the cases with a postoperative cancer residue.
32898699	9	115	theme	glycans	1175:1181	arg1	One					1162:1164	One	1162:1164	One	1162:1164	One of these glycans was detected as differentially abundant in sera of the validation cohort.
32898699	9	115	theme	glycans	1175:1181	arg1	glycans					1175:1181	these glycans	1169:1181	these glycans	1169:1181	One of these glycans was detected as differentially abundant in sera of the validation cohort.
32898699	2	116	theme	high-grade	329:338	arg1	cancer					361:366	advanced stage, high-grade non-mucinous ovarian cancer	313:366	cancer	361:366	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32898699	7	117	theme	68	956:957	arg1	signals					1001:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	68 (tissue) and 63 (serum) N-glycan spectral signals	956:1007	The MS analysis yielded a consecutive detection of 68 (tissue) and 63 (serum) N-glycan spectral signals.
32898699	16	118	theme	differences	2293:2303	arg1	identification					2275:2288	identification	2275:2288	identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy	2275:2455	Our report deals with identification of differences in N-glycosylation of proteins in tissue and serum samples from the individuals showing sensitivity or resistance to platinum/taxane-based chemotherapy.
32898699	2	119	theme	based	387:391	arg1	chemotherapy					393:404	platinum/taxane based chemotherapy	371:404	platinum/taxane based chemotherapy	371:404	Our investigation further expands on this topic through the examination of N-glycans, which could be associated with the resistance of advanced stage, high-grade non-mucinous ovarian cancer to platinum/taxane based chemotherapy.
32143591	0	0	theme	microarray-based	94:109	arg1	study					111:115	a lectin microarray-based study	85:115	a lectin microarray-based study	85:115	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.
32143591	6	1	theme	well-differentiated	1251:1269	arg1	components					1271:1280	well-differentiated components	1251:1280	well-differentiated components	1251:1280	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	2	dep	Narcissus	1039:1047	arg1	pseudonarcissus					1049:1063	pseudonarcissus	1049:1063	pseudonarcissus	1049:1063	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	0	3	theme	lectin	87:92	arg1	study					111:115	a lectin microarray-based study	85:115	a lectin microarray-based study	85:115	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.
32143591	6	4	theme	Narcissus	1039:1047	arg1	lectins					1026:1032	Four lectins	1021:1032	Four lectins	1021:1032	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	4	theme	Narcissus	1039:1047	arg1	NPA					1077:1079	NPA	1077:1079	NPA	1077:1079	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	4	theme	Narcissus	1039:1047	arg1	agglutinin					1065:1074	Narcissus pseudonarcissus agglutinin	1039:1074	Narcissus pseudonarcissus agglutinin (NPA)	1039:1080	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	7	5	theme	moderately-differentiated	1419:1443	arg1	components					1445:1454	moderately-differentiated components	1419:1454	moderately-differentiated components than in well-differentiated ones	1419:1487	Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones.
32143591	4	6	dep	METHODS	513:519	arg1	analyzed					524:531	analyzed	524:531	analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule	524:763	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	5	7	theme	mannosyl	821:828	arg1	β-1,2-N-acetylglucosaminyltransferase					851:887	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	821:887	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	821:895	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	5	7	theme	mannosyl	821:828	arg1	MGAT1					890:894	MGAT1	890:894	MGAT1	890:894	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	8	8	from	expression	1556:1565	arg1	components					1627:1636	moderately-differentiated components	1601:1636	moderately-differentiated components	1601:1636	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	8	9	theme	MGAT1	1581:1585	arg1	expression					1587:1596	decreased MGAT1 expression	1571:1596	decreased MGAT1 expression in moderately-differentiated components	1571:1636	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	6	10	theme	binding	1306:1312	arg1	specificity					1314:1324	binding specificity	1306:1324	binding specificity to high-mannose glycans	1306:1348	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	9	11	theme	tumors	1703:1708	arg1	components					1689:1698	moderately-differentiated components	1663:1698	moderately-differentiated components of tumors	1663:1708	Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
32143591	10	12	theme	high-mannose	1881:1892	arg1	glycans					1894:1900	high-mannose glycans	1881:1900	high-mannose glycans	1881:1900	CONCLUSION Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans.
32143591	4	13	theme	resected	533:540	arg1	n = 50					557:562	n = 50	557:562	n = 50	557:562	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	4	13	theme	resected	533:540	arg1	specimens					546:554	resected HCC specimens	533:554	resected HCC specimens (n = 50)	533:563	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	5	14	gly	-glycoprotein	837:849	arg1	-glycoprotein					837:849	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	821:887	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	821:895	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	7	15	from	components	1445:1454	arg1	ones					1484:1487	well-differentiated ones	1464:1487	well-differentiated ones	1464:1487	Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones.
32143591	0	16	theme	Altered	0:6	arg1	glycosylation					8:20	Altered glycosylation	0:20	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma	0:82	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.
32143591	6	17	theme	nivalis	1109:1115	arg1	lectins					1026:1032	Four lectins	1021:1032	Four lectins	1021:1032	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	17	theme	nivalis	1109:1115	arg1	agglutinin					1117:1126	Galanthus nivalis agglutinin	1099:1126	Galanthus nivalis agglutinin	1099:1126	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	5	18	theme	α-1,3-	830:835	arg1	β-1,2-N-acetylglucosaminyltransferase					851:887	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	821:887	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	821:895	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	5	18	theme	α-1,3-	830:835	arg1	MGAT1					890:894	MGAT1	890:894	MGAT1	890:894	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	5	19	theme	high-mannose	954:965	arg1	glycans					967:973	high-mannose glycans	954:973	high-mannose glycans	954:973	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	9	20	theme	intrahepatic	1730:1741	arg1	metastasis					1743:1752	intrahepatic metastasis	1730:1752	intrahepatic metastasis	1730:1752	Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
32143591	0	21	dep	study	111:115	arg1	glycosylation					8:20	Altered glycosylation	0:20	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma	0:82	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.
32143591	6	22	theme	HCC	1233:1235	arg1	components					1219:1228	moderately-differentiated components	1193:1228	moderately-differentiated components of HCC	1193:1235	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	4	23	theme	HCC	542:544	arg1	n = 50					557:562	n = 50	557:562	n = 50	557:562	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	4	23	theme	HCC	542:544	arg1	specimens					546:554	resected HCC specimens	533:554	resected HCC specimens (n = 50)	533:563	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	7	24	theme	greater	1401:1407	arg1	extent					1409:1414	a greater extent	1399:1414	a greater extent	1399:1414	Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones.
32143591	6	25	theme	high-mannose	1329:1340	arg1	glycans					1342:1348	high-mannose glycans	1329:1348	high-mannose glycans	1329:1348	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	7	26	theme	well-differentiated	1464:1482	arg1	ones					1484:1487	well-differentiated ones	1464:1487	well-differentiated ones	1464:1487	Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones.
32143591	5	27	theme	hybrid-type	990:1000	arg1	N-glycans					1002:1010	hybrid-type N-glycans	990:1010	hybrid-type N-glycans	990:1010	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	3	28	theme	same	432:435	arg1	nodule					437:442	the same nodule	428:442	the same nodule	428:442	Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation.
32143591	6	29	theme	Galanthus	1099:1107	arg1	lectins					1026:1032	Four lectins	1021:1032	Four lectins	1021:1032	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	29	theme	Galanthus	1099:1107	arg1	agglutinin					1117:1126	Galanthus nivalis agglutinin	1099:1126	Galanthus nivalis agglutinin	1099:1126	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	8	30	theme	moderately-differentiated	1601:1625	arg1	components					1627:1636	moderately-differentiated components	1601:1636	moderately-differentiated components	1601:1636	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	3	31	theme	related	483:489	arg1	glycosyltransferase					463:481	glycosyltransferase	463:481	glycosyltransferase related to the glycosylation	463:510	Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation.
32143591	3	32	theme	HCC	417:419	arg1	dedifferentiation					396:412	dedifferentiation	396:412	dedifferentiation of HCC within the same nodule	396:442	Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation.
32143591	5	33	theme	essential	910:918	arg1	staining					809:816	immunohistochemical staining	789:816	immunohistochemical staining	789:816	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	5	33	theme	essential	910:918	arg1	glycosyltransferase					920:938	an essential glycosyltransferase	907:938	an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans	907:1010	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	10	34	theme	CONCLUSION	1791:1800	arg1	Dedifferentiation					1802:1818	CONCLUSION Dedifferentiation	1791:1818	CONCLUSION Dedifferentiation of well-differentiated HCC	1791:1845	CONCLUSION Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans.
32143591	1	35	theme	BACKGROUND	118:127	arg1	glycosylation					137:149	BACKGROUND Altered glycosylation	118:149	BACKGROUND Altered glycosylation associated with hepatocellular carcinoma (HCC)	118:196	BACKGROUND Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented.
32143591	6	36	theme	moderately-differentiated	1193:1217	arg1	components					1219:1228	moderately-differentiated components	1193:1228	moderately-differentiated components of HCC	1193:1235	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	4	37	theme	glycan	632:637	arg1	profiles					639:646	glycan profiles	632:646	glycan profiles	632:646	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	5	38	theme	immunohistochemical	789:807	arg1	glycosyltransferase					920:938	an essential glycosyltransferase	907:938	an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans	907:1010	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	5	38	theme	immunohistochemical	789:807	arg1	staining					809:816	immunohistochemical staining	789:816	immunohistochemical staining	789:816	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	1	39	theme	Altered	129:135	arg1	glycosylation					137:149	BACKGROUND Altered glycosylation	118:149	BACKGROUND Altered glycosylation associated with hepatocellular carcinoma (HCC)	118:196	BACKGROUND Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented.
32143591	4	40	theme	well-	695:699	arg1	components					731:740	well- and moderately-differentiated components	695:740	well- and moderately-differentiated components within the same nodule	695:763	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	6	41	theme	Concanavalin	1083:1094	arg1	A					1096:1096	Concanavalin A	1083:1096	Concanavalin A	1083:1096	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	41	theme	Concanavalin	1083:1094	arg1	lectins					1026:1032	Four lectins	1021:1032	Four lectins	1021:1032	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	4	42	theme	same	753:756	arg1	nodule					758:763	the same nodule	749:763	the same nodule	749:763	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	6	43	dep	lectins	1026:1032	arg1	agglutinin					1065:1074	Narcissus pseudonarcissus agglutinin	1039:1074	Narcissus pseudonarcissus agglutinin (NPA)	1039:1080	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	43	dep	lectins	1026:1032	arg1	A					1096:1096	Concanavalin A	1083:1096	Concanavalin A	1083:1096	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	43	dep	lectins	1026:1032	arg1	lectins					1026:1032	Four lectins	1021:1032	Four lectins	1021:1032	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	43	dep	lectins	1026:1032	arg1	agglutinin					1151:1160	Calystegia sepium agglutinin	1133:1160	Calystegia sepium agglutinin	1133:1160	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	43	dep	lectins	1026:1032	arg1	NPA					1077:1079	NPA	1077:1079	NPA	1077:1079	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	43	dep	lectins	1026:1032	arg1	agglutinin					1117:1126	Galanthus nivalis agglutinin	1099:1126	Galanthus nivalis agglutinin	1099:1126	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	4	44	theme	moderately-differentiated	705:729	arg1	components					731:740	well- and moderately-differentiated components	695:740	well- and moderately-differentiated components within the same nodule	695:763	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	0	45	theme	carcinoma	74:82	arg1	dedifferentiation					38:54	dedifferentiation	38:54	dedifferentiation of hepatocellular carcinoma	38:82	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.
32143591	4	46	theme	lectin	571:576	arg1	microarray					578:587	lectin microarray	571:587	lectin microarray	571:587	METHODS We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule.
32143591	10	47	theme	HCC	1843:1845	arg1	Dedifferentiation					1802:1818	CONCLUSION Dedifferentiation	1791:1818	CONCLUSION Dedifferentiation of well-differentiated HCC	1791:1845	CONCLUSION Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans.
32143591	9	48	theme	poor	1775:1778	arg1	prognosis					1780:1788	poor prognosis	1775:1788	poor prognosis	1775:1788	Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
32143591	0	49	theme	hepatocellular	59:72	arg1	carcinoma					74:82	hepatocellular carcinoma	59:82	hepatocellular carcinoma	59:82	Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study.
32143591	3	50	theme	study	345:349	arg1	aim					333:335	the aim	329:335	the aim of this study	329:349	Therefore, the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation.
32143591	10	51	from	increase	1869:1876	arg1	glycans					1894:1900	high-mannose glycans	1881:1900	high-mannose glycans	1881:1900	CONCLUSION Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans.
32143591	8	52	theme	Immunohistochemical	1490:1508	arg1	staining					1510:1517	Immunohistochemical staining	1490:1517	Immunohistochemical staining	1490:1517	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	9	53	theme	Low	1639:1641	arg1	expression					1649:1658	Low MGAT1 expression	1639:1658	Low MGAT1 expression in moderately-differentiated components of tumors	1639:1708	Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
32143591	2	54	theme	few	227:229	arg1	reports					231:237	few reports	227:237	few reports	227:237	However, few reports have investigated the association between dedifferentiation and glycosylation.
32143591	6	55	from	lectins	1026:1032	arg1	RESULTS					1013:1019	RESULTS	1013:1019	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin	1013:1160	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	8	56	from	expression	1587:1596	arg1	components					1627:1636	moderately-differentiated components	1601:1636	moderately-differentiated components	1601:1636	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	9	57	theme	MGAT1	1643:1647	arg1	expression					1649:1658	Low MGAT1 expression	1639:1658	Low MGAT1 expression in moderately-differentiated components of tumors	1639:1708	Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
32143591	9	58	from	expression	1649:1658	arg1	components					1689:1698	moderately-differentiated components	1663:1698	moderately-differentiated components of tumors	1663:1708	Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
32143591	1	59	theme	hepatocellular	167:180	arg1	HCC					193:195	HCC	193:195	HCC	193:195	BACKGROUND Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented.
32143591	1	59	theme	hepatocellular	167:180	arg1	carcinoma					182:190	hepatocellular carcinoma	167:190	hepatocellular carcinoma (HCC)	167:196	BACKGROUND Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented.
32143591	8	60	theme	decreased	1571:1579	arg1	expression					1587:1596	decreased MGAT1 expression	1571:1596	decreased MGAT1 expression in moderately-differentiated components	1571:1636	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	5	61	theme	-glycoprotein	837:849	arg1	β-1,2-N-acetylglucosaminyltransferase					851:887	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase	821:887	mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1)	821:895	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	5	61	theme	-glycoprotein	837:849	arg1	MGAT1					890:894	MGAT1	890:894	MGAT1	890:894	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	8	62	theme	NPA	1552:1554	arg1	expression					1556:1565	significantly increased NPA expression	1528:1565	significantly increased NPA expression	1528:1565	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	10	63	theme	well-differentiated	1823:1841	arg1	HCC					1843:1845	well-differentiated HCC	1823:1845	well-differentiated HCC	1823:1845	CONCLUSION Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans.
32143591	6	64	theme	sepium	1144:1149	arg1	lectins					1026:1032	Four lectins	1021:1032	Four lectins	1021:1032	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	64	theme	sepium	1144:1149	arg1	agglutinin					1151:1160	Calystegia sepium agglutinin	1133:1160	Calystegia sepium agglutinin	1133:1160	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	5	65	theme	β-1,2-N-acetylglucosaminyltransferase	851:887	arg1	glycosyltransferase					920:938	an essential glycosyltransferase	907:938	an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans	907:1010	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	5	65	theme	β-1,2-N-acetylglucosaminyltransferase	851:887	arg1	staining					809:816	immunohistochemical staining	789:816	immunohistochemical staining	789:816	Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
32143591	11	66	theme	HCC	1953:1955	arg1	dedifferentiation					1932:1948	the dedifferentiation	1928:1948	the dedifferentiation of HCC	1928:1955	MGAT1 may play a role in the dedifferentiation of HCC.
32143591	9	67	theme	moderately-differentiated	1663:1687	arg1	components					1689:1698	moderately-differentiated components	1663:1698	moderately-differentiated components of tumors	1663:1708	Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
32143591	8	68	theme	increased	1542:1550	arg1	expression					1556:1565	significantly increased NPA expression	1528:1565	significantly increased NPA expression	1528:1565	Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components.
32143591	6	69	theme	Calystegia	1133:1142	arg1	lectins					1026:1032	Four lectins	1021:1032	Four lectins	1021:1032	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
32143591	6	69	theme	Calystegia	1133:1142	arg1	agglutinin					1151:1160	Calystegia sepium agglutinin	1133:1160	Calystegia sepium agglutinin	1133:1160	RESULTS Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans.
31875397	0	0	theme	Neuropeptides	101:113	arg1	Discovery					59:67	Discovery	59:67	Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System	59:146	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	7	1	theme	collected	1308:1316	arg1	scans					1322:1326	the collected HCD scans	1304:1326	the collected HCD scans	1304:1326	In addition, 91 novel putative neuropeptides have been discovered based on the collected HCD scans.
31875397	4	2	theme	HCD	770:772	arg1	spectra					781:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	1	3	theme	model	179:183	arg1	organisms					185:193	model organisms	179:193	model organisms	179:193	Crustaceans are commonly used model organisms to study neuromodulation.
31875397	4	4	theme	neuropeptides	629:641	arg1	discovery					603:611	the discovery	599:611	the discovery of glycosylated neuropeptides with an enrichment-free approach	599:674	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	0	5	theme	Glycosylated	88:99	arg1	Neuropeptides					101:113	N- and O-Linked Glycosylated Neuropeptides	72:113	N- and O-Linked Glycosylated Neuropeptides	72:113	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	9	6	gly	glycosylated	1619:1630	arg1	neuropeptides					1632:1644	novel glycosylated neuropeptides	1613:1644	novel glycosylated neuropeptides	1613:1644	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	5	7	from	detection	794:802	arg1	scans					835:839	the HCD scans	827:839	the HCD scans	827:839	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	8	8	from	report	1480:1485	arg1	discovery					1540:1548	the discovery	1536:1548	the discovery of additional neuropeptides	1536:1576	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	8	8	from	report	1480:1485	arg1	neuropeptides					1503:1515	glycosylated neuropeptides	1490:1515	glycosylated neuropeptides in crustaceans	1490:1530	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	4	9	theme	glycosylated	616:627	arg1	neuropeptides					629:641	glycosylated neuropeptides	616:641	glycosylated neuropeptides with an enrichment-free approach	616:674	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	9	10	theme	crustacean	1665:1674	arg1	peptidome					1676:1684	the crustacean peptidome	1661:1684	the crustacean peptidome	1661:1684	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	8	11	dep	approach	1341:1348	arg1	coupling					1351:1358	coupling	1351:1358	coupling	1351:1358	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	5	12	gly	glycosylated	1020:1031	arg1	neuropeptides					1033:1045	glycosylated neuropeptides	1020:1045	glycosylated neuropeptides that are buried in nonglycosylated peptides	1020:1089	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	9	13	theme	novel	1697:1701	arg1	insights					1703:1710	novel insights	1697:1710	novel insights into future neuropeptide functional studies	1697:1754	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	3	14	theme	important	546:554	arg1	role					556:559	an important role	543:559	an important role	543:559	This is in part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification, even though glycosylation has been shown to play an important role in neuromodulation.
31875397	0	15	theme	Nervous	133:139	arg1	System					141:146	the Crustacean Nervous System	118:146	the Crustacean Nervous System	118:146	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	6	16	dep	N-linked	1103:1110	arg1	neuropeptides					1141:1153	glycosylated neuropeptides	1128:1153	glycosylated neuropeptides	1128:1153	Overall, 4 N-linked and 14 O-linked glycosylated neuropeptides have been identified for the first time in the crustacean nervous system.
31875397	1	17	used	used	174:177	arg2	Crustaceans					149:159	Crustaceans	149:159	Crustaceans	149:159	Crustaceans are commonly used model organisms to study neuromodulation.
31875397	4	18	theme	higher-energy	732:744	arg1	spectra					781:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	6	19	theme	first	1184:1188	arg1	time					1190:1193	the first time	1180:1193	the first time in the crustacean nervous system	1180:1226	Overall, 4 N-linked and 14 O-linked glycosylated neuropeptides have been identified for the first time in the crustacean nervous system.
31875397	0	20	theme	Crustacean	122:131	arg1	System					141:146	the Crustacean Nervous System	118:146	the Crustacean Nervous System	118:146	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	0	21	from	Discovery	59:67	arg1	System					141:146	the Crustacean Nervous System	118:146	the Crustacean Nervous System	118:146	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	5	22	theme	HCD	831:833	arg1	scans					835:839	the HCD scans	827:839	the HCD scans	827:839	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	4	23	gly	glycosylated	616:627	arg1	neuropeptides					629:641	glycosylated neuropeptides	616:641	glycosylated neuropeptides with an enrichment-free approach	616:674	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	4	24	theme	ions	715:718	arg1	advantage					684:692	advantage	684:692	advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra	684:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	0	25	theme	Mass	24:27	arg1	Approach					42:49	Signature-Ion-Triggered Mass Spectrometry Approach	0:49	Signature-Ion-Triggered Mass Spectrometry Approach	0:49	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	5	26	gly	nonglycosylated	1066:1080	arg1	peptides					1082:1089	nonglycosylated peptides	1066:1089	nonglycosylated peptides	1066:1089	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	7	27	theme	HCD	1318:1320	arg1	scans					1322:1326	the collected HCD scans	1304:1326	the collected HCD scans	1304:1326	In addition, 91 novel putative neuropeptides have been discovered based on the collected HCD scans.
31875397	5	28	theme	oxonium	811:817	arg1	ions					819:822	the oxonium ions	807:822	the oxonium ions	807:822	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	5	29	theme	glycosylated	1020:1031	arg1	neuropeptides					1033:1045	glycosylated neuropeptides	1020:1045	glycosylated neuropeptides that are buried in nonglycosylated peptides	1020:1089	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	8	30	from	neuropeptides	1503:1515	arg1	crustaceans					1520:1530	crustaceans	1520:1530	crustaceans	1520:1530	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	3	31	theme	post-translational	461:478	arg1	modification					480:491	this intricate low-abundance post-translational modification	432:491	this intricate low-abundance post-translational modification	432:491	This is in part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification, even though glycosylation has been shown to play an important role in neuromodulation.
31875397	0	32	theme	Signature-Ion-Triggered	0:22	arg1	Approach					42:49	Signature-Ion-Triggered Mass Spectrometry Approach	0:49	Signature-Ion-Triggered Mass Spectrometry Approach	0:49	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	8	33	theme	hybrid	1334:1339	arg1	approach					1341:1348	This hybrid approach	1329:1348	This hybrid approach	1329:1348	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	5	34	theme	neuropeptides	1033:1045	arg1	information					1005:1015	structural information	994:1015	structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides	994:1089	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	8	35	theme	neuropeptides	1564:1576	arg1	discovery					1540:1548	the discovery	1536:1548	the discovery of additional neuropeptides	1536:1576	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	8	35	theme	neuropeptides	1564:1576	arg1	neuropeptides					1503:1515	glycosylated neuropeptides	1490:1515	glycosylated neuropeptides in crustaceans	1490:1530	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	3	36	theme	sensitive	390:398	arg1	methods					400:406	sensitive methods	390:406	sensitive methods that enable deciphering this intricate low-abundance post-translational modification	390:491	This is in part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification, even though glycosylation has been shown to play an important role in neuromodulation.
31875397	8	37	theme	additional	1553:1562	arg1	neuropeptides					1564:1576	additional neuropeptides	1553:1576	additional neuropeptides	1553:1576	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	8	38	theme	neuropeptide	1381:1392	arg1	discovery					1394:1402	neuropeptide discovery	1381:1402	neuropeptide discovery	1381:1402	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	8	39	theme	glycosylated	1490:1501	arg1	neuropeptides					1503:1515	glycosylated neuropeptides	1490:1515	glycosylated neuropeptides in crustaceans	1490:1530	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	3	40	theme	methods	400:406	arg1	lack					382:385	a lack	380:385	a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification	380:491	This is in part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification, even though glycosylation has been shown to play an important role in neuromodulation.
31875397	5	41	theme	nonglycosylated	1066:1080	arg1	peptides					1082:1089	nonglycosylated peptides	1066:1089	nonglycosylated peptides	1066:1089	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	9	42	theme	glycosylated	1619:1630	arg1	neuropeptides					1632:1644	novel glycosylated neuropeptides	1613:1644	novel glycosylated neuropeptides	1613:1644	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	2	43	theme	neuropeptide	329:340	arg1	glycosylation					342:354	neuropeptide glycosylation	329:354	neuropeptide glycosylation	329:354	Despite numerous reported crustacean neuropeptide families and their functions, there has been no report on neuropeptide glycosylation.
31875397	8	44	from	discovery	1540:1548	arg1	crustaceans					1520:1530	crustaceans	1520:1530	crustaceans	1520:1530	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	5	45	theme	electron-transfer/higher-energy	890:920	arg1	EThcD					946:950	EThcD	946:950	EThcD	946:950	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	5	45	theme	electron-transfer/higher-energy	890:920	arg1	dissociation					932:943	electron-transfer/higher-energy collision dissociation	890:943	electron-transfer/higher-energy collision dissociation (EThcD)	890:951	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	3	46	theme	intricate	437:445	arg1	modification					480:491	this intricate low-abundance post-translational modification	432:491	this intricate low-abundance post-translational modification	432:491	This is in part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification, even though glycosylation has been shown to play an important role in neuromodulation.
31875397	9	47	theme	future	1717:1722	arg1	studies					1748:1754	future neuropeptide functional studies	1717:1754	future neuropeptide functional studies	1717:1754	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	6	48	gly	glycosylated	1128:1139	arg1	neuropeptides					1141:1153	glycosylated neuropeptides	1128:1153	glycosylated neuropeptides	1128:1153	Overall, 4 N-linked and 14 O-linked glycosylated neuropeptides have been identified for the first time in the crustacean nervous system.
31875397	5	49	theme	collision	922:930	arg1	EThcD					946:950	EThcD	946:950	EThcD	946:950	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	5	49	theme	collision	922:930	arg1	dissociation					932:943	electron-transfer/higher-energy collision dissociation	890:943	electron-transfer/higher-energy collision dissociation (EThcD)	890:951	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	4	50	theme	oxonium	707:713	arg1	ions					715:718	signature oxonium ions	697:718	signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra	697:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	3	51	theme	low-abundance	447:459	arg1	modification					480:491	this intricate low-abundance post-translational modification	432:491	this intricate low-abundance post-translational modification	432:491	This is in part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification, even though glycosylation has been shown to play an important role in neuromodulation.
31875397	7	52	theme	novel	1245:1249	arg1	neuropeptides					1260:1272	91 novel putative neuropeptides	1242:1272	91 novel putative neuropeptides	1242:1272	In addition, 91 novel putative neuropeptides have been discovered based on the collected HCD scans.
31875397	8	53	theme	targeted	1408:1415	arg1	strategy					1417:1424	targeted strategy	1408:1424	targeted strategy for glycosylation characterization	1408:1459	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	7	54	theme	putative	1251:1258	arg1	neuropeptides					1260:1272	91 novel putative neuropeptides	1242:1272	91 novel putative neuropeptides	1242:1272	In addition, 91 novel putative neuropeptides have been discovered based on the collected HCD scans.
31875397	4	55	theme	signature	697:705	arg1	ions					715:718	signature oxonium ions	697:718	signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra	697:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	0	56	theme	N-	72:73	arg1	Neuropeptides					101:113	N- and O-Linked Glycosylated Neuropeptides	72:113	N- and O-Linked Glycosylated Neuropeptides	72:113	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	5	57	theme	ions	819:822	arg1	detection					794:802	The detection	790:802	The detection of the oxonium ions in the HCD scans	790:839	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	9	58	theme	novel	1613:1617	arg1	neuropeptides					1632:1644	novel glycosylated neuropeptides	1613:1644	novel glycosylated neuropeptides	1613:1644	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	6	59	theme	crustacean	1202:1211	arg1	system					1221:1226	the crustacean nervous system	1198:1226	the crustacean nervous system	1198:1226	Overall, 4 N-linked and 14 O-linked glycosylated neuropeptides have been identified for the first time in the crustacean nervous system.
31875397	4	60	theme	MS/MS	775:779	arg1	spectra					781:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	5	61	theme	glycan	850:855	arg1	attachment					857:866	glycan attachment	850:866	glycan attachment to peptides	850:878	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	2	62	theme	crustacean	247:256	arg1	families					271:278	numerous reported crustacean neuropeptide families	229:278	numerous reported crustacean neuropeptide families	229:278	Despite numerous reported crustacean neuropeptide families and their functions, there has been no report on neuropeptide glycosylation.
31875397	2	63	theme	neuropeptide	258:269	arg1	families					271:278	numerous reported crustacean neuropeptide families	229:278	numerous reported crustacean neuropeptide families	229:278	Despite numerous reported crustacean neuropeptide families and their functions, there has been no report on neuropeptide glycosylation.
31875397	9	64	theme	neuropeptides	1632:1644	arg1	elucidation					1598:1608	The elucidation	1594:1608	The elucidation of novel glycosylated neuropeptides	1594:1644	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	5	65	theme	structural	994:1003	arg1	information					1005:1015	structural information	994:1015	structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides	994:1089	The detection of the oxonium ions in the HCD scans suggests glycan attachment to peptides, allowing electron-transfer/higher-energy collision dissociation (EThcD) to be performed to selectively elucidate structural information of glycosylated neuropeptides that are buried in nonglycosylated peptides.
31875397	8	66	gly	glycosylated	1490:1501	arg1	neuropeptides					1503:1515	glycosylated neuropeptides	1490:1515	glycosylated neuropeptides in crustaceans	1490:1530	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	2	67	theme	reported	238:245	arg1	families					271:278	numerous reported crustacean neuropeptide families	229:278	numerous reported crustacean neuropeptide families	229:278	Despite numerous reported crustacean neuropeptide families and their functions, there has been no report on neuropeptide glycosylation.
31875397	8	68	theme	first	1474:1478	arg1	report					1480:1485	the first report	1470:1485	the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides	1470:1576	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	9	69	theme	neuropeptide	1724:1735	arg1	studies					1748:1754	future neuropeptide functional studies	1717:1754	future neuropeptide functional studies	1717:1754	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	9	70	theme	functional	1737:1746	arg1	studies					1748:1754	future neuropeptide functional studies	1717:1754	future neuropeptide functional studies	1717:1754	The elucidation of novel glycosylated neuropeptides sheds light on the crustacean peptidome and offers novel insights into future neuropeptide functional studies.
31875397	8	71	theme	shotgun	1362:1368	arg1	method					1370:1375	a shotgun method	1360:1375	a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization	1360:1459	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	2	72	theme	numerous	229:236	arg1	families					271:278	numerous reported crustacean neuropeptide families	229:278	numerous reported crustacean neuropeptide families	229:278	Despite numerous reported crustacean neuropeptide families and their functions, there has been no report on neuropeptide glycosylation.
31875397	6	73	theme	nervous	1213:1219	arg1	system					1221:1226	the crustacean nervous system	1198:1226	the crustacean nervous system	1198:1226	Overall, 4 N-linked and 14 O-linked glycosylated neuropeptides have been identified for the first time in the crustacean nervous system.
31875397	8	74	theme	glycosylation	1430:1442	arg1	characterization					1444:1459	glycosylation characterization	1430:1459	glycosylation characterization	1430:1459	This hybrid approach, coupling a shotgun method for neuropeptide discovery and targeted strategy for glycosylation characterization, enables the first report on glycosylated neuropeptides in crustaceans and the discovery of additional neuropeptides simultaneously.
31875397	4	75	theme	enrichment-free	651:665	arg1	approach					667:674	an enrichment-free approach	648:674	an enrichment-free approach	648:674	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	0	76	theme	O-Linked	79:86	arg1	Neuropeptides					101:113	N- and O-Linked Glycosylated Neuropeptides	72:113	N- and O-Linked Glycosylated Neuropeptides	72:113	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	6	77	theme	glycosylated	1128:1139	arg1	neuropeptides					1141:1153	glycosylated neuropeptides	1128:1153	glycosylated neuropeptides	1128:1153	Overall, 4 N-linked and 14 O-linked glycosylated neuropeptides have been identified for the first time in the crustacean nervous system.
31875397	4	78	with	neuropeptides	629:641	arg1	approach					667:674	an enrichment-free approach	648:674	an enrichment-free approach	648:674	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	6	79	from	time	1190:1193	arg1	system					1221:1226	the crustacean nervous system	1198:1226	the crustacean nervous system	1198:1226	Overall, 4 N-linked and 14 O-linked glycosylated neuropeptides have been identified for the first time in the crustacean nervous system.
31875397	4	80	theme	dissociation	756:767	arg1	spectra					781:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
31875397	2	81	from	report	319:324	arg1	glycosylation					342:354	neuropeptide glycosylation	329:354	neuropeptide glycosylation	329:354	Despite numerous reported crustacean neuropeptide families and their functions, there has been no report on neuropeptide glycosylation.
31875397	3	82	theme	due	373:375	arg1	part					368:371	part	368:371	part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification	368:491	This is in part due to a lack of sensitive methods that enable deciphering this intricate low-abundance post-translational modification, even though glycosylation has been shown to play an important role in neuromodulation.
31875397	0	83	theme	Spectrometry	29:40	arg1	Approach					42:49	Signature-Ion-Triggered Mass Spectrometry Approach	0:49	Signature-Ion-Triggered Mass Spectrometry Approach	0:49	Signature-Ion-Triggered Mass Spectrometry Approach Enabled Discovery of N- and O-Linked Glycosylated Neuropeptides in the Crustacean Nervous System.
31875397	4	84	theme	collision	746:754	arg1	spectra					781:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	higher-energy collision dissociation (HCD) MS/MS spectra	732:787	Here, we describe the discovery of glycosylated neuropeptides with an enrichment-free approach, taking advantage of signature oxonium ions produced in higher-energy collision dissociation (HCD) MS/MS spectra.
32663509	7	0	theme	CMP-Neu5Ac	1614:1623	arg1	content					1625:1631	CMP-Neu5Ac content	1614:1631	CMP-Neu5Ac content	1614:1631	Furthermore, B3GNT2 overexpression enhanced intracellular UDP-GlcNAc and CMP-Neu5Ac content while slightly lowering UDP-Gal content.
32663509	10	1	theme	transmembrane	2253:2265	arg1	domains					2283:2289	transmembrane and cytoplasmic domains	2253:2289	transmembrane and cytoplasmic domains	2253:2289	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	10	2	theme	initial	2041:2047	arg1	expression					2049:2058	initial expression	2041:2058	initial expression of B4GALT1	2041:2069	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	8	3	theme	nucleotide	1810:1819	arg1	product					1847:1853	its downstream product	1832:1853	its downstream product	1832:1853	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	8	3	theme	nucleotide	1810:1819	arg1	levels					1795:1800	the intracellular levels	1777:1800	the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac	1777:1865	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	8	3	theme	nucleotide	1810:1819	arg1	CMP-Neu5Ac					1856:1865	CMP-Neu5Ac	1856:1865	CMP-Neu5Ac	1856:1865	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	1	4	theme	therapeutic	255:265	arg1	proteins					279:286	therapeutic recombinant proteins	255:286	therapeutic recombinant proteins	255:286	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	10	5	theme	domain	2240:2245	arg1	section					2200:2206	a section	2198:2206	a section of the B3GNT2 trans-Golgi lumen domain	2198:2245	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	8	6	with	B3GNT2	1727:1732	arg1	disposition					1742:1752	no disposition	1739:1752	no disposition	1739:1752	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	1	7	theme	proteins	279:286	arg1	properties					241:250	properties	241:250	properties	241:250	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	1	7	theme	proteins	279:286	arg1	functions					227:235	various cellular functions	210:235	various cellular functions	210:235	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	5	8	theme	B4GALT1	813:819	arg1	overexpression					795:808	overexpression	795:808	overexpression of B4GALT1	795:819	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	9	9	dep	levels	1966:1971	arg1	either					1922:1927	either	1922:1927	either	1922:1927	Furthermore, we were unable to overexpress B4GALT1 at either the transcriptional or translational levels following initial B3GNT2 expression.
32663509	7	10	theme	B3GNT2	1554:1559	arg1	overexpression					1561:1574	B3GNT2 overexpression	1554:1574	B3GNT2 overexpression	1554:1574	Furthermore, B3GNT2 overexpression enhanced intracellular UDP-GlcNAc and CMP-Neu5Ac content while slightly lowering UDP-Gal content.
32663509	10	11	theme	cytoplasmic	2271:2281	arg1	domains					2283:2289	transmembrane and cytoplasmic domains	2253:2289	transmembrane and cytoplasmic domains	2253:2289	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	5	12	theme	B3GNT2	905:910	arg1	overexpression					887:900	overexpression	887:900	overexpression of B3GNT2 in EPO-expressing CHO cells	887:938	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	6	13	theme	exposed	1435:1441	arg1	residues					1450:1457	exposed GlcNAc residues	1435:1457	exposed GlcNAc residues on the N-glycans	1435:1474	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	6	14	from	GlcNAc	1533:1538	arg1	termination					1500:1510	premature termination	1490:1510	premature termination of many N-glycans at GlcNAc	1490:1538	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	3	15	theme	per	600:602	arg1	glycan					604:609	≥4 repeats per glycan	589:609	≥4 repeats per glycan	589:609	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	3	15	theme	per	600:602	arg1	content					580:586	the LacNAc content	569:586	the LacNAc content (≥4 repeats per glycan)	569:610	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	1	16	theme	various	210:216	arg1	functions					227:235	various cellular functions	210:235	various cellular functions	210:235	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	11	17	theme	N-glycan	2623:2630	arg1	patterns					2632:2639	the resulting N-glycan patterns	2609:2639	the resulting N-glycan patterns	2609:2639	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	4	18	theme	EPO-expressing	739:752	arg1	cells					782:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	3	19	theme	recombinant	615:625	arg1	protein					631:637	recombinant EPO protein	615:637	recombinant EPO protein	615:637	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	6	20	theme	present	1274:1280	arg1	motifs					1267:1272	the binding domain motifs	1248:1272	the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases	1248:1338	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	4	21	theme	hamster	762:768	arg1	cells					782:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	10	22	theme	B3GNT2	2183:2188	arg1	accumulation					2157:2168	the accumulation	2153:2168	the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain	2153:2245	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	5	23	theme	recombinant	968:978	arg1	EPO					980:982	the recombinant EPO	964:982	the recombinant EPO LacNAc content	964:997	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	6	24	theme	domain	1260:1265	arg1	motifs					1267:1272	the binding domain motifs	1248:1272	the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases	1248:1338	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	0	25	theme	Chinese	67:73	arg1	cells					89:93	Chinese hamster ovary cells	67:93	Chinese hamster ovary cells	67:93	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	11	26	from	influence	2455:2463	arg1	activities					2487:2496	activities	2487:2496	activities	2487:2496	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	26	from	influence	2455:2463	arg1	expression					2472:2481	expression	2472:2481	expression	2472:2481	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	5	27	theme	EPO-expressing	915:928	arg1	cells					934:938	EPO-expressing CHO cells	915:938	EPO-expressing CHO cells	915:938	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	0	28	from	challenges	22:31	arg1	cells					89:93	Chinese hamster ovary cells	67:93	Chinese hamster ovary cells	67:93	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	0	29	theme	ovary	83:87	arg1	cells					89:93	Chinese hamster ovary cells	67:93	Chinese hamster ovary cells	67:93	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	5	30	theme	knock-out-B3GNT2	1178:1193	arg1	lines					1215:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	1	31	theme	poly-LacNAc	168:178	arg1	units					181:185	multiple N-acetyllactosamine (poly-LacNAc) units	138:185	multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins	138:286	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	11	32	theme	glycosyltransferases	2411:2430	arg1	addition					2375:2382	the addition	2371:2382	the addition of one or more recombinant glycosyltransferases	2371:2430	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	33	contain	have	2436:2439	arg1	addition					2375:2382	the addition	2371:2382	the addition of one or more recombinant glycosyltransferases	2371:2430	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	33	contain	have	2436:2439	arg2	influence					2455:2463	an unexpected influence	2441:2463	an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns	2441:2639	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	34	theme	sugar	2556:2560	arg1	levels					2562:2567	the nucleotide sugar levels	2541:2567	the nucleotide sugar levels	2541:2567	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	0	35	theme	N-glycan	46:53	arg1	pathways					55:62	extending N-glycan pathways	36:62	extending N-glycan pathways	36:62	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	0	36	theme	hamster	75:81	arg1	cells					89:93	Chinese hamster ovary cells	67:93	Chinese hamster ovary cells	67:93	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	0	37	theme	Metabolic	0:8	arg1	challenges					22:31	Metabolic engineering challenges	0:31	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.	0:94	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	5	38	theme	LacNAc	984:989	arg1	content					991:997	the recombinant EPO LacNAc content	964:997	the recombinant EPO LacNAc content	964:997	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	2	39	theme	LacNAc	478:483	arg1	units					485:489	LacNAc units	478:489	LacNAc units	478:489	Previous studies indicated that β-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β-1,4-galactotransferase 1 (B4GALT1) are two of the primary glycosyltransferases involved in generating LacNAc units.
32663509	3	40	theme	current	499:505	arg1	study					507:511	the current study	495:511	the current study	495:511	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	5	41	theme	large	853:857	arg1	glycans					859:865	large glycans	853:865	large glycans	853:865	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	3	42	theme	LacNAc	573:578	arg1	glycan					604:609	≥4 repeats per glycan	589:609	≥4 repeats per glycan	589:609	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	3	42	theme	LacNAc	573:578	arg1	content					580:586	the LacNAc content	569:586	the LacNAc content (≥4 repeats per glycan)	569:610	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	9	43	theme	transcriptional	1933:1947	arg1	levels					1966:1971	either the transcriptional or translational levels	1922:1971	levels	1966:1971	Furthermore, we were unable to overexpress B4GALT1 at either the transcriptional or translational levels following initial B3GNT2 expression.
32663509	2	44	theme	glycosyltransferases	434:453	arg1	glycosyltransferases					434:453	the primary glycosyltransferases	422:453	the primary glycosyltransferases involved in generating LacNAc units	422:489	Previous studies indicated that β-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β-1,4-galactotransferase 1 (B4GALT1) are two of the primary glycosyltransferases involved in generating LacNAc units.
32663509	2	44	theme	glycosyltransferases	434:453	arg1	two					415:417	two	415:417	two	415:417	Previous studies indicated that β-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β-1,4-galactotransferase 1 (B4GALT1) are two of the primary glycosyltransferases involved in generating LacNAc units.
32663509	6	45	theme	many	1515:1518	arg1	N-glycans					1520:1528	many N-glycans	1515:1528	many N-glycans	1515:1528	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	5	46	theme	cell	1210:1213	arg1	lines					1215:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	0	47	theme	extending	36:44	arg1	pathways					55:62	extending N-glycan pathways	36:62	extending N-glycan pathways	36:62	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	7	48	theme	UDP-Gal	1657:1663	arg1	content					1665:1671	UDP-Gal content	1657:1671	UDP-Gal content	1657:1671	Furthermore, B3GNT2 overexpression enhanced intracellular UDP-GlcNAc and CMP-Neu5Ac content while slightly lowering UDP-Gal content.
32663509	9	49	theme	translational	1952:1964	arg1	levels					1966:1971	either the transcriptional or translational levels	1922:1971	levels	1966:1971	Furthermore, we were unable to overexpress B4GALT1 at either the transcriptional or translational levels following initial B3GNT2 expression.
32663509	0	50	theme	pathways	55:62	arg1	challenges					22:31	Metabolic engineering challenges	0:31	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.	0:94	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	10	51	theme	lumen	2234:2238	arg1	domain					2240:2245	the B3GNT2 trans-Golgi lumen domain	2211:2245	the B3GNT2 trans-Golgi lumen domain	2211:2245	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	1	52	theme	cellular	218:225	arg1	functions					227:235	various cellular functions	210:235	various cellular functions	210:235	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	1	53	theme	N-acetyllactosamine	147:165	arg1	units					181:185	multiple N-acetyllactosamine (poly-LacNAc) units	138:185	multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins	138:286	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	9	54	theme	B3GNT2	1991:1996	arg1	expression					1998:2007	initial B3GNT2 expression	1983:2007	initial B3GNT2 expression	1983:2007	Furthermore, we were unable to overexpress B4GALT1 at either the transcriptional or translational levels following initial B3GNT2 expression.
32663509	11	55	theme	intra-network	2348:2360	arg1	process					2362:2368	a very complex intra-network process	2333:2368	a very complex intra-network process	2333:2368	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	55	theme	intra-network	2348:2360	arg1	glycosylation					2316:2328	glycosylation	2316:2328	glycosylation	2316:2328	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	8	56	theme	B3GNT2	1727:1732	arg1	form					1719:1722	the form	1715:1722	the form of B3GNT2 with no disposition	1715:1752	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	7	57	theme	intracellular	1585:1597	arg1	UDP-GlcNAc					1599:1608	intracellular UDP-GlcNAc	1585:1608	intracellular UDP-GlcNAc	1585:1608	Furthermore, B3GNT2 overexpression enhanced intracellular UDP-GlcNAc and CMP-Neu5Ac content while slightly lowering UDP-Gal content.
32663509	8	58	theme	no	1739:1740	arg1	disposition					1742:1752	no disposition	1739:1752	no disposition	1739:1752	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	1	59	theme	recombinant	267:277	arg1	proteins					279:286	therapeutic recombinant proteins	255:286	therapeutic recombinant proteins	255:286	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	5	60	theme	CHO	930:932	arg1	cells					934:938	EPO-expressing CHO cells	915:938	EPO-expressing CHO cells	915:938	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	11	61	theme	unexpected	2444:2453	arg1	influence					2455:2463	an unexpected influence	2441:2463	an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns	2441:2639	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	2	62	theme	Previous	289:296	arg1	studies					298:304	Previous studies	289:304	Previous studies	289:304	Previous studies indicated that β-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β-1,4-galactotransferase 1 (B4GALT1) are two of the primary glycosyltransferases involved in generating LacNAc units.
32663509	4	63	theme	dual-overexpression	669:687	arg1	role					650:653	the role	646:653	the role of single and dual-overexpression of B3GNT2 and B4GALT1	646:709	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	10	64	theme	B4GALT1	2063:2069	arg1	expression					2049:2058	initial expression	2041:2058	initial expression of B4GALT1	2041:2069	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	8	65	from	UDP-GlcNAc	1701:1710	arg1	form					1719:1722	the form	1715:1722	the form of B3GNT2 with no disposition	1715:1752	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	4	66	theme	B3GNT2	692:697	arg1	single					658:663	single	658:663	single	658:663	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	6	67	attach	present	1274:1280	arg1	B3GNT2					1285:1290	B3GNT2	1285:1290	B3GNT2	1285:1290	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	6	67	attach	present	1274:1280	arg2	motifs					1267:1272	the binding domain motifs	1248:1272	the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases	1248:1338	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	6	68	theme	GlcNAc	1443:1448	arg1	residues					1450:1457	exposed GlcNAc residues	1435:1457	exposed GlcNAc residues on the N-glycans	1435:1474	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	3	69	theme	repeats	592:598	arg1	glycan					604:609	≥4 repeats per glycan	589:609	≥4 repeats per glycan	589:609	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	3	69	theme	repeats	592:598	arg1	content					580:586	the LacNAc content	569:586	the LacNAc content (≥4 repeats per glycan)	569:610	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	8	70	theme	downstream	1836:1845	arg1	product					1847:1853	its downstream product	1832:1853	its downstream product	1832:1853	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	8	70	theme	downstream	1836:1845	arg1	CMP-Neu5Ac					1856:1865	CMP-Neu5Ac	1856:1865	CMP-Neu5Ac	1856:1865	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	5	71	theme	glycans	859:865	arg1	levels					843:848	the levels	839:848	the levels of large glycans	839:865	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	72	theme	undetectable	1106:1117	arg1	sialylation					1119:1129	nearly undetectable sialylation	1099:1129	nearly undetectable sialylation	1099:1129	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	3	73	theme	EPO	627:629	arg1	protein					631:637	recombinant EPO protein	615:637	recombinant EPO protein	615:637	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	5	74	theme	recombinant	870:880	arg1	EPO					882:884	recombinant EPO	870:884	recombinant EPO	870:884	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	11	75	theme	glycosyltransferases	2501:2520	arg1	activities					2487:2496	activities	2487:2496	activities	2487:2496	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	75	theme	glycosyltransferases	2501:2520	arg1	expression					2472:2481	expression	2472:2481	expression	2472:2481	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	76	theme	resulting	2613:2621	arg1	patterns					2632:2639	the resulting N-glycan patterns	2609:2639	the resulting N-glycan patterns	2609:2639	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	4	77	theme	single	658:663	arg1	role					650:653	the role	646:653	the role of single and dual-overexpression of B3GNT2 and B4GALT1	646:709	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	6	78	theme	endogenous	1392:1401	arg1	β1,4-galactosyltransferases					1403:1429	endogenous β1,4-galactosyltransferases	1392:1429	endogenous β1,4-galactosyltransferases	1392:1429	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	10	79	theme	transcriptional	2100:2114	arg1	analysis					2134:2141	transcriptional and translational analysis	2100:2141	transcriptional and translational analysis	2100:2141	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	4	80	theme	recombinant	727:737	arg1	cells					782:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	10	81	theme	translational	2120:2132	arg1	analysis					2134:2141	transcriptional and translational analysis	2100:2141	transcriptional and translational analysis	2100:2141	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	5	82	theme	Gals	1089:1092	arg1	structures					1057:1066	GlcNAc structures	1050:1066	GlcNAc structures	1050:1066	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	82	theme	Gals	1089:1092	arg1	sialylation					1119:1129	nearly undetectable sialylation	1099:1129	nearly undetectable sialylation	1099:1129	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	82	theme	Gals	1089:1092	arg1	number					1079:1084	a limited number	1069:1084	a limited number of Gals	1069:1092	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	6	83	theme	motifs	1267:1272	arg1	nature					1238:1243	the nature	1234:1243	the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases	1234:1338	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	4	84	theme	Chinese	754:760	arg1	cells					782:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	10	85	theme	truncated	2173:2181	arg1	B3GNT2					2183:2188	truncated B3GNT2	2173:2188	truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain	2173:2245	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	6	86	theme	premature	1490:1498	arg1	termination					1500:1510	premature termination	1490:1510	premature termination of many N-glycans at GlcNAc	1490:1538	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	1	87	theme	multiple	138:145	arg1	units					181:185	multiple N-acetyllactosamine (poly-LacNAc) units	138:185	multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins	138:286	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	10	88	theme	trans-Golgi	2222:2232	arg1	domain					2240:2245	the B3GNT2 trans-Golgi lumen domain	2211:2245	the B3GNT2 trans-Golgi lumen domain	2211:2245	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	6	89	theme	binding	1252:1258	arg1	motifs					1267:1272	the binding domain motifs	1248:1272	the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases	1248:1338	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	11	90	theme	patterns	2632:2639	arg1	modifications					2592:2604	unexpected modifications	2581:2604	unexpected modifications of the resulting N-glycan patterns	2581:2639	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	4	91	theme	B4GALT1	703:709	arg1	single					658:663	single	658:663	single	658:663	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	5	92	theme	sialyltransferases	1159:1176	arg1	lines					1215:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	93	from	overexpression	887:900	arg1	cells					934:938	EPO-expressing CHO cells	915:938	EPO-expressing CHO cells	915:938	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	94	located	observed	1147:1154	arg2	sialylation					1119:1129	nearly undetectable sialylation	1099:1129	nearly undetectable sialylation	1099:1129	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	94	located	observed	1147:1154	arg1	lines					1215:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	95	theme	overexpression	1195:1208	arg1	lines					1215:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	11	96	theme	nucleotide	2545:2554	arg1	levels					2562:2567	the nucleotide sugar levels	2541:2567	the nucleotide sugar levels	2541:2567	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	6	97	from	residues	1450:1457	arg1	N-glycans					1466:1474	the N-glycans	1462:1474	the N-glycans	1462:1474	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	10	98	theme	B3GNT2	2215:2220	arg1	domain					2240:2245	the B3GNT2 trans-Golgi lumen domain	2211:2245	the B3GNT2 trans-Golgi lumen domain	2211:2245	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	11	99	theme	recombinant	2399:2409	arg1	glycosyltransferases					2411:2430	one or more recombinant glycosyltransferases	2387:2430	one or more recombinant glycosyltransferases	2387:2430	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	100	theme	unexpected	2581:2590	arg1	modifications					2592:2604	unexpected modifications	2581:2604	unexpected modifications of the resulting N-glycan patterns	2581:2639	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	0	101	theme	engineering	10:20	arg1	challenges					22:31	Metabolic engineering challenges	0:31	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.	0:94	Metabolic engineering challenges of extending N-glycan pathways in Chinese hamster ovary cells.
32663509	5	102	theme	EPO	980:982	arg1	content					991:997	the recombinant EPO LacNAc content	964:997	the recombinant EPO LacNAc content	964:997	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	11	103	theme	complex	2340:2346	arg1	process					2362:2368	a very complex intra-network process	2333:2368	a very complex intra-network process	2333:2368	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	11	103	theme	complex	2340:2346	arg1	glycosylation					2316:2328	glycosylation	2316:2328	glycosylation	2316:2328	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
32663509	4	104	theme	ovary	770:774	arg1	cells					782:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	1	105	theme	mammalian	99:107	arg1	cells					109:113	mammalian cells	99:113	mammalian cells	99:113	In mammalian cells, N-glycans may include multiple N-acetyllactosamine (poly-LacNAc) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins.
32663509	8	106	theme	sink	1692:1695	arg1	presence					1678:1685	The presence	1674:1685	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition	1674:1752	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	4	107	theme	CHO	777:779	arg1	cells					782:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	recombinant EPO-expressing Chinese hamster ovary (CHO) cells	727:786	Next, the role of single and dual-overexpression of B3GNT2 and B4GALT1 was explored in recombinant EPO-expressing Chinese hamster ovary (CHO) cells.
32663509	6	108	theme	N-glycans	1520:1528	arg1	termination					1500:1510	premature termination	1490:1510	premature termination of many N-glycans at GlcNAc	1490:1538	Considering the nature of the binding domain motifs present on B3GNT2, which evolved from β1,3-galactosyltransferases, its overexpression may have competed and inhibited endogenous β1,4-galactosyltransferases for exposed GlcNAc residues on the N-glycans, resulting in premature termination of many N-glycans at GlcNAc.
32663509	2	109	theme	primary	426:432	arg1	glycosyltransferases					434:453	the primary glycosyltransferases	422:453	the primary glycosyltransferases involved in generating LacNAc units	422:489	Previous studies indicated that β-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2) and β-1,4-galactotransferase 1 (B4GALT1) are two of the primary glycosyltransferases involved in generating LacNAc units.
32663509	5	110	theme	limited	1071:1077	arg1	number					1079:1084	a limited number	1069:1084	a limited number of Gals	1069:1092	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	10	111	theme	B3GNT2	2024:2029	arg1	Expression					2010:2019	Expression	2010:2019	Expression of B3GNT2 following initial expression of B4GALT1	2010:2069	Expression of B3GNT2 following initial expression of B4GALT1 was also problematic in that transcriptional and translational analysis indicated the accumulation of truncated B3GNT2 missing a section of the B3GNT2 trans-Golgi lumen domain while transmembrane and cytoplasmic domains were present.
32663509	3	112	theme	sialyltransferase	527:543	arg1	genes					545:549	sialyltransferase genes	527:549	sialyltransferase genes	527:549	In the current study, knocking out sialyltransferase genes slightly enhanced the LacNAc content (≥4 repeats per glycan) on recombinant EPO protein.
32663509	9	113	theme	initial	1983:1989	arg1	expression					1998:2007	initial B3GNT2 expression	1983:2007	initial B3GNT2 expression	1983:2007	Furthermore, we were unable to overexpress B4GALT1 at either the transcriptional or translational levels following initial B3GNT2 expression.
32663509	8	114	theme	intracellular	1781:1793	arg1	levels					1795:1800	the intracellular levels	1777:1800	the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac	1777:1865	The presence of a sink for UDP-GlcNAc in the form of B3GNT2 with no disposition may have also elevated the intracellular levels of this nucleotide as well as its downstream product, CMP-Neu5Ac.
32663509	5	115	theme	GlcNAc	1050:1055	arg1	structures					1057:1066	GlcNAc structures	1050:1066	GlcNAc structures	1050:1066	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	116	gly	sialylation	1119:1129	arg1	lines					1215:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	sialyltransferases knock-out-B3GNT2 overexpression cell lines	1159:1219	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	5	116	gly	sialylation	1119:1129	arg1	Gals					1089:1092	Gals	1089:1092	Gals	1089:1092	While overexpression of B4GALT1 slightly enhanced the levels of large glycans on recombinant EPO, overexpression of B3GNT2 in EPO-expressing CHO cells significantly decreased the recombinant EPO LacNAc content, resulting in N-glycans terminating primarily with GlcNAc structures, a limited number of Gals, and nearly undetectable sialylation, which was also observed in sialyltransferases knock-out-B3GNT2 overexpression cell lines.
32663509	11	117	dep	expression	2472:2481	arg1	the					2468:2470	the	2468:2470	the	2468:2470	Given that glycosylation is a very complex intra-network process, the addition of one or more recombinant glycosyltransferases may have an unexpected influence on the expression and activities of glycosyltransferases, which can disrupt the nucleotide sugar levels and lead to unexpected modifications of the resulting N-glycan patterns.
33340519	5	0	theme	glycoforms	730:739	arg1	panel					705:709	a panel	703:709	a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications	703:829	We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications.
33340519	8	1	theme	spike	1154:1158	arg1	binding					1160:1166	viral spike binding	1148:1166	viral spike binding	1148:1166	Overall, ACE2 glycosylation does not significantly influence viral spike binding.
33340519	4	2	theme	SARS-CoV-2	666:675	arg1	spike					683:687	SARS-CoV-2 viral spike	666:687	SARS-CoV-2 viral spike	666:687	We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike.
33340519	9	3	theme	virus	1311:1315	arg1	binding					1317:1323	virus binding	1311:1323	virus binding	1311:1323	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	8	4	theme	viral	1148:1152	arg1	binding					1160:1166	viral spike binding	1148:1166	viral spike binding	1148:1166	Overall, ACE2 glycosylation does not significantly influence viral spike binding.
33340519	0	5	from	Influence	7:15	arg1	Recognition					57:67	SARS-CoV-2 Recognition	46:67	SARS-CoV-2 Recognition	46:67	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.
33340519	3	6	theme	human	467:471	arg1	enzyme					515:520	angiotensin-converting enzyme 2	492:522	angiotensin-converting enzyme 2 (ACE2)	492:529	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	6	theme	human	467:471	arg1	receptor					482:489	the human cellular receptor	463:489	the human cellular receptor	463:489	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	9	7	theme	SARS-CoV-2	1234:1243	arg1	pathobiology					1218:1229	the pathobiology	1214:1229	the pathobiology of SARS-CoV-2	1214:1243	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	3	8	theme	cellular	473:480	arg1	enzyme					515:520	angiotensin-converting enzyme 2	492:522	angiotensin-converting enzyme 2 (ACE2)	492:529	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	8	theme	cellular	473:480	arg1	receptor					482:489	the human cellular receptor	463:489	the human cellular receptor	463:489	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	5	9	gly	glycoforms	730:739	arg1	ACE2					725:728	engineered ACE2 glycoforms	714:739	engineered ACE2 glycoforms	714:739	We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications.
33340519	6	10	theme	glycosylation	866:878	arg1	impact					851:856	the impact	847:856	the impact of ACE2 glycosylation on S binding	847:891	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	6	11	from	impact	851:856	arg1	binding					885:891	S binding	883:891	S binding	883:891	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	2	12	from	differences	218:228	arg1	glycosylation					237:249	the glycosylation	233:249	the glycosylation of target human cells	233:271	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	4	13	theme	glycosylation	609:621	arg1	state					623:627	the glycosylation state	605:627	the glycosylation state of ACE2	605:635	We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike.
33340519	6	14	theme	ACE2	861:864	arg1	glycosylation					866:878	ACE2 glycosylation	861:878	ACE2 glycosylation	861:878	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	5	15	theme	glycan	810:815	arg1	modifications					817:829	the site-specific glycan modifications	792:829	the site-specific glycan modifications	792:829	We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications.
33340519	2	16	theme	variable	368:375	arg1	acid					333:336	sialic acid	326:336	sialic acid which is a common, and highly variable, terminal modification of glycans	326:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	16	theme	variable	368:375	arg1	modification					387:398	a common, and highly variable, terminal modification	347:398	a common, and highly variable, terminal modification of glycans	347:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	4	17	with	interaction	649:659	arg1	spike					683:687	SARS-CoV-2 viral spike	666:687	SARS-CoV-2 viral spike	666:687	We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike.
33340519	9	18	theme	glycosylation	1197:1209	arg1	role					1189:1192	any role	1185:1192	any role of glycosylation in the pathobiology of SARS-CoV-2	1185:1243	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	2	19	theme	cells	267:271	arg1	glycosylation					237:249	the glycosylation	233:249	the glycosylation of target human cells	233:271	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	3	20	theme	viral	416:420	arg1	glycoprotein					428:439	viral spike glycoprotein	416:439	The viral spike glycoprotein (S) of SARS-CoV-2	412:457	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	9	21	from	role	1189:1192	arg1	pathobiology					1218:1229	the pathobiology	1214:1229	the pathobiology of SARS-CoV-2	1214:1243	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	8	22	theme	ACE2	1096:1099	arg1	glycosylation					1101:1113	ACE2 glycosylation	1096:1113	ACE2 glycosylation	1096:1113	Overall, ACE2 glycosylation does not significantly influence viral spike binding.
33340519	3	23	dep	glycosylated	548:559	arg1	both					535:538	both	535:538	both	535:538	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	0	24	theme	Subtle	0:5	arg1	Influence					7:15	Subtle Influence	0:15	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.	0:68	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.
33340519	6	25	theme	oligomannose-type	951:967	arg1	glycans					969:975	hypersialylated or oligomannose-type glycans	932:975	hypersialylated or oligomannose-type glycans slightly impeding the interaction	932:1009	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	4	26	gly	glycosylation	609:621	arg1	ACE2					632:635	ACE2	632:635	ACE2	632:635	We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike.
33340519	1	27	theme	SARS-CoV-2	86:95	arg1	infection					97:105	SARS-CoV-2 infection	86:105	SARS-CoV-2 infection	86:105	The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive.
33340519	4	28	theme	ACE2	632:635	arg1	state					623:627	the glycosylation state	605:627	the glycosylation state of ACE2	605:635	We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike.
33340519	2	29	gly	glycosylation	237:249	arg1	cells					267:271	target human cells	254:271	target human cells	254:271	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	6	30	gly	hypersialylated	932:946	arg1	glycans					969:975	hypersialylated or oligomannose-type glycans	932:975	hypersialylated or oligomannose-type glycans slightly impeding the interaction	932:1009	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	1	31	theme	infection	97:105	arg1	severity					74:81	The severity	70:81	The severity of SARS-CoV-2 infection	70:105	The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive.
33340519	1	31	theme	infection	97:105	arg1	variable					117:124	variable	117:124	variable	117:124	The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive.
33340519	5	32	theme	site-specific	796:808	arg1	modifications					817:829	the site-specific glycan modifications	792:829	the site-specific glycan modifications	792:829	We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications.
33340519	2	33	theme	glycans	403:409	arg1	acid					333:336	sialic acid	326:336	sialic acid which is a common, and highly variable, terminal modification of glycans	326:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	33	theme	glycans	403:409	arg1	modification					387:398	a common, and highly variable, terminal modification	347:398	a common, and highly variable, terminal modification of glycans	347:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	6	34	theme	hypersialylated	932:946	arg1	glycans					969:975	hypersialylated or oligomannose-type glycans	932:975	hypersialylated or oligomannose-type glycans slightly impeding the interaction	932:1009	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	7	35	theme	SARS-CoV-2	1067:1076	arg1	binding					1078:1084	SARS-CoV-2 binding	1067:1084	SARS-CoV-2 binding	1067:1084	In contrast, deglycosylation of ACE2 did not influence SARS-CoV-2 binding.
33340519	3	36	gly	glycosylated	548:559	arg1	enzyme					515:520	angiotensin-converting enzyme 2	492:522	angiotensin-converting enzyme 2 (ACE2)	492:529	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	36	gly	glycosylated	548:559	arg1	receptor					482:489	the human cellular receptor	463:489	the human cellular receptor	463:489	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	36	gly	glycosylated	548:559	arg1	S					442:442	The viral spike glycoprotein (S)	412:443	The viral spike glycoprotein (S) of SARS-CoV-2	412:457	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	0	37	theme	Processing	32:41	arg1	Influence					7:15	Subtle Influence	0:15	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.	0:68	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.
33340519	4	38	theme	viral	677:681	arg1	spike					683:687	SARS-CoV-2 viral spike	666:687	SARS-CoV-2 viral spike	666:687	We therefore sought to investigate whether the glycosylation state of ACE2 impacts the interaction with SARS-CoV-2 viral spike.
33340519	3	39	theme	spike	422:426	arg1	glycoprotein					428:439	viral spike glycoprotein	416:439	The viral spike glycoprotein (S) of SARS-CoV-2	412:457	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	2	40	theme	terminal	378:385	arg1	acid					333:336	sialic acid	326:336	sialic acid which is a common, and highly variable, terminal modification of glycans	326:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	40	theme	terminal	378:385	arg1	modification					387:398	a common, and highly variable, terminal modification	347:398	a common, and highly variable, terminal modification of glycans	347:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	0	41	theme	Glycan	25:30	arg1	Processing					32:41	ACE2 Glycan Processing	20:41	ACE2 Glycan Processing	20:41	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.
33340519	9	42	gly	glycosylation	1197:1209	arg1	SARS-CoV-2					1234:1243	SARS-CoV-2	1234:1243	SARS-CoV-2	1234:1243	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	0	43	theme	ACE2	20:23	arg1	Processing					32:41	ACE2 Glycan Processing	20:41	ACE2 Glycan Processing	20:41	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.
33340519	3	44	theme	glycoprotein	428:439	arg1	S					442:442	The viral spike glycoprotein (S)	412:443	The viral spike glycoprotein (S) of SARS-CoV-2	412:457	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	0	45	theme	SARS-CoV-2	46:55	arg1	Recognition					57:67	SARS-CoV-2 Recognition	46:67	SARS-CoV-2 Recognition	46:67	Subtle Influence of ACE2 Glycan Processing on SARS-CoV-2 Recognition.
33340519	2	46	contain	has	301:303	arg2	capacity					309:316	the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans	305:409	the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans	305:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	46	contain	has	301:303	arg1	SARS-CoV-2					290:299	SARS-CoV-2	290:299	SARS-CoV-2	290:299	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	9	47	from	impact	1275:1280	arg1	binding					1317:1323	virus binding	1311:1323	virus binding	1311:1323	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	3	48	gly	glycoprotein	428:439	arg1	glycoprotein					428:439	viral spike glycoprotein	416:439	The viral spike glycoprotein (S) of SARS-CoV-2	412:457	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	49	theme	SARS-CoV-2	448:457	arg1	enzyme					515:520	angiotensin-converting enzyme 2	492:522	angiotensin-converting enzyme 2 (ACE2)	492:529	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	49	theme	SARS-CoV-2	448:457	arg1	receptor					482:489	the human cellular receptor	463:489	the human cellular receptor	463:489	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	49	theme	SARS-CoV-2	448:457	arg1	S					442:442	The viral spike glycoprotein (S)	412:443	The viral spike glycoprotein (S) of SARS-CoV-2	412:457	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	5	50	theme	mass	764:767	arg1	spectrometry					769:780	mass spectrometry	764:780	mass spectrometry	764:780	We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications.
33340519	7	51	theme	ACE2	1044:1047	arg1	deglycosylation					1025:1039	deglycosylation	1025:1039	deglycosylation of ACE2	1025:1047	In contrast, deglycosylation of ACE2 did not influence SARS-CoV-2 binding.
33340519	6	52	theme	S	883:883	arg1	binding					885:891	S binding	883:891	S binding	883:891	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	9	53	theme	receptor	1285:1292	arg1	glycosylation					1294:1306	receptor glycosylation	1285:1306	receptor glycosylation	1285:1306	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	2	54	theme	sialic	326:331	arg1	acid					333:336	sialic acid	326:336	sialic acid which is a common, and highly variable, terminal modification of glycans	326:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	54	theme	sialic	326:331	arg1	modification					387:398	a common, and highly variable, terminal modification	347:398	a common, and highly variable, terminal modification of glycans	347:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	55	theme	potential	191:199	arg1	differences					218:228	differences	218:228	differences in the glycosylation of target human cells	218:271	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	55	theme	potential	191:199	arg1	contribution					201:212	One potential contribution	187:212	One potential contribution	187:212	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	56	theme	human	261:265	arg1	cells					267:271	target human cells	254:271	target human cells	254:271	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	7	57	gly	deglycosylation	1025:1039	arg1	ACE2					1044:1047	ACE2	1044:1047	ACE2	1044:1047	In contrast, deglycosylation of ACE2 did not influence SARS-CoV-2 binding.
33340519	6	58	with	sensitivity	915:925	arg1	glycans					969:975	hypersialylated or oligomannose-type glycans	932:975	hypersialylated or oligomannose-type glycans slightly impeding the interaction	932:1009	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
33340519	3	59	theme	angiotensin-converting	492:513	arg1	enzyme					515:520	angiotensin-converting enzyme 2	492:522	angiotensin-converting enzyme 2 (ACE2)	492:529	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	59	theme	angiotensin-converting	492:513	arg1	ACE2					525:528	ACE2	525:528	ACE2	525:528	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	3	59	theme	angiotensin-converting	492:513	arg1	receptor					482:489	the human cellular receptor	463:489	the human cellular receptor	463:489	The viral spike glycoprotein (S) of SARS-CoV-2 and the human cellular receptor, angiotensin-converting enzyme 2 (ACE2) are both densely glycosylated.
33340519	9	60	theme	immediate	1265:1273	arg1	impact					1275:1280	its immediate impact	1261:1280	its immediate impact of receptor glycosylation on virus binding	1261:1323	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	2	61	theme	target	254:259	arg1	cells					267:271	target human cells	254:271	target human cells	254:271	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	5	62	theme	engineered	714:723	arg1	glycoforms					730:739	engineered ACE2 glycoforms	714:739	engineered ACE2 glycoforms	714:739	We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications.
33340519	2	63	theme	common	349:354	arg1	acid					333:336	sialic acid	326:336	sialic acid which is a common, and highly variable, terminal modification of glycans	326:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	2	63	theme	common	349:354	arg1	modification					387:398	a common, and highly variable, terminal modification	347:398	a common, and highly variable, terminal modification of glycans	347:409	One potential contribution are differences in the glycosylation of target human cells, particularly as SARS-CoV-2 has the capacity to bind sialic acid which is a common, and highly variable, terminal modification of glycans.
33340519	5	64	theme	ACE2	725:728	arg1	glycoforms					730:739	engineered ACE2 glycoforms	714:739	engineered ACE2 glycoforms	714:739	We generated a panel of engineered ACE2 glycoforms which were analyzed by mass spectrometry to reveal the site-specific glycan modifications.
33340519	9	65	theme	glycosylation	1294:1306	arg1	impact					1275:1280	its immediate impact	1261:1280	its immediate impact of receptor glycosylation on virus binding	1261:1323	We suggest that any role of glycosylation in the pathobiology of SARS-CoV-2 will lie beyond its immediate impact of receptor glycosylation on virus binding.
33340519	1	66	theme	molecular	138:146	arg1	basis					148:152	the molecular basis	134:152	the molecular basis for this effect	134:168	The severity of SARS-CoV-2 infection is highly variable and yet the molecular basis for this effect remains elusive.
33340519	6	67	theme	subtle	908:913	arg1	sensitivity					915:925	a subtle sensitivity	906:925	a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction	906:1009	We then probed the impact of ACE2 glycosylation on S binding and revealed a subtle sensitivity with hypersialylated or oligomannose-type glycans slightly impeding the interaction.
32039582	11	0	from	study	1877:1881	arg1	lines					1863:1867	different cell lines	1848:1867	different cell lines	1848:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	4	1	theme	O-glycans	580:588	arg1	analysis					551:558	in-depth structural analysis	531:558	in-depth structural analysis	531:558	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	4	1	theme	O-glycans	580:588	arg1	quantitation					564:575	quantitation	564:575	quantitation	564:575	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	5	2	theme	isolated	664:671	arg1	glycoproteins					687:699	isolated cell membrane glycoproteins	664:699	isolated cell membrane glycoproteins	664:699	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	8	3	theme	monosaccharide	1215:1228	arg1	compositions					1230:1241	The monosaccharide compositions	1211:1241	The monosaccharide compositions	1211:1241	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	6	4	from	proteins	925:932	arg1	interference					878:889	interference	878:889	interference from small molecules and degraded proteins	878:932	Released O-glycans were purified by an optimized protocol to eliminate interference from small molecules and degraded proteins.
32039582	5	5	theme	membrane	678:685	arg1	glycoproteins					687:699	isolated cell membrane glycoproteins	664:699	isolated cell membrane glycoproteins	664:699	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	7	6	theme	membrane	1131:1138	arg1	fractions					1140:1148	the same cell membrane fractions	1117:1148	the same cell membrane fractions	1117:1148	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	8	7	theme	detected	1263:1270	arg1	O-glycans					1272:1280	the detected O-glycans	1259:1280	the detected O-glycans	1259:1280	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	8	8	theme	mass	1350:1353	arg1	MS/MS					1369:1373	MS/MS	1369:1373	MS/MS	1369:1373	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	8	8	theme	mass	1350:1353	arg1	spectrometry					1355:1366	tandem mass spectrometry	1343:1366	tandem mass spectrometry (MS/MS)	1343:1374	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	11	9	theme	cell	1858:1861	arg1	lines					1863:1867	different cell lines	1848:1867	different cell lines	1848:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	7	10	theme	same	1121:1124	arg1	fractions					1140:1148	the same cell membrane fractions	1117:1148	the same cell membrane fractions	1117:1148	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	2	11	theme	advanced	302:309	arg1	separation					311:320	advanced separation and mass spectrometry techniques	302:353	separation	311:320	N-Glycans have been extensively characterized using advanced separation and mass spectrometry techniques.
32039582	1	12	theme	cell	202:205	arg1	membrane					207:214	cell membrane	202:214	cell membrane	202:214	Proteins on cell membrane are modified by N- and O-glycans.
32039582	1	13	mod	modified	220:227	arg3	N-					232:233	N-	232:233	N-	232:233	Proteins on cell membrane are modified by N- and O-glycans.
32039582	1	13	mod	modified	220:227	arg1	Proteins					190:197	Proteins	190:197	Proteins on cell membrane	190:214	Proteins on cell membrane are modified by N- and O-glycans.
32039582	1	13	mod	modified	220:227	arg3	O-glycans					239:247	O-glycans	239:247	O-glycans	239:247	Proteins on cell membrane are modified by N- and O-glycans.
32039582	0	14	from	Membrane	70:77	arg1	Analysis					16:23	Deep Structural Analysis	0:23	Deep Structural Analysis	0:23	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	0	14	from	Membrane	70:77	arg1	Quantitation					29:40	Quantitation	29:40	Quantitation	29:40	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	7	15	attach	isolated	1103:1110	arg1	fractions					1140:1148	the same cell membrane fractions	1117:1148	the same cell membrane fractions	1117:1148	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	7	15	attach	isolated	1103:1110	arg2	N-glycans					1077:1085	the N-glycans	1073:1085	the N-glycans	1073:1085	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	11	16	theme	specific	1886:1893	arg1	changes					1904:1910	specific O-glycan changes	1886:1910	specific O-glycan changes during cell differentiation	1886:1938	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	5	17	theme	PNGase	752:757	arg1	digestion					761:769	PNGase F digestion	752:769	PNGase F digestion	752:769	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	11	18	from	quantification	1795:1808	arg1	lines					1863:1867	different cell lines	1848:1867	different cell lines	1848:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	0	19	theme	Cell	149:152	arg1	Type					154:157	Cell Type	149:157	Cell Type	149:157	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	11	20	theme	unique	1813:1818	arg1	O-glycans					1833:1841	unique cell surface O-glycans	1813:1841	unique cell surface O-glycans from different cell lines	1813:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	7	21	theme	graphitized	1034:1044	arg1	column					1059:1064	a porous graphitized carbon (PGC) column	1025:1064	a porous graphitized carbon (PGC) column	1025:1064	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	9	22	theme	complete	1588:1595	arg1	structures					1597:1606	their complete structures	1582:1606	their complete structures	1582:1606	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	11	23	from	identification	1776:1789	arg1	lines					1863:1867	different cell lines	1848:1867	different cell lines	1848:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	0	24	from	Analysis	16:23	arg1	Membrane					70:77	Cell Membrane	65:77	Cell Membrane	65:77	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	11	25	theme	surface	1825:1831	arg1	O-glycans					1833:1841	unique cell surface O-glycans	1813:1841	unique cell surface O-glycans from different cell lines	1813:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	0	26	theme	High	86:89	arg1	Abundances					91:100	High Abundances	86:100	High Abundances	86:100	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	9	27	with	library	1569:1575	arg1	times					1640:1644	retention times	1630:1644	retention times	1630:1644	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	9	27	with	library	1569:1575	arg1	structures					1597:1606	their complete structures	1582:1606	their complete structures	1582:1606	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	9	27	with	library	1569:1575	arg1	masses					1618:1623	accurate masses	1609:1623	accurate masses	1609:1623	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	5	28	theme	Folch	775:779	arg1	extraction					781:790	Folch extraction	775:790	Folch extraction	775:790	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	7	29	theme	nanoLC-chip-QTOF	985:1000	arg1	spectrometer					1007:1018	a nanoLC-chip-QTOF mass spectrometer	983:1018	a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column	983:1064	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	0	30	from	Quantitation	29:40	arg1	Membrane					70:77	Cell Membrane	65:77	Cell Membrane	65:77	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	3	31	theme	enzymes	428:434	arg1	lack					410:413	the lack	406:413	the lack of universal enzymes to release them	406:450	However, O-glycans remain a challenge, because of the lack of universal enzymes to release them and the large background abundances of N-glycans.
32039582	3	31	theme	enzymes	428:434	arg1	abundances					477:486	the large background abundances	456:486	the large background abundances of N-glycans	456:499	However, O-glycans remain a challenge, because of the lack of universal enzymes to release them and the large background abundances of N-glycans.
32039582	0	32	theme	Deep	0:3	arg1	Analysis					16:23	Deep Structural Analysis	0:23	Deep Structural Analysis	0:23	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	4	33	theme	structural	540:549	arg1	analysis					551:558	in-depth structural analysis	531:558	in-depth structural analysis	531:558	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	3	34	theme	large	460:464	arg1	abundances					477:486	the large background abundances	456:486	the large background abundances of N-glycans	456:499	However, O-glycans remain a challenge, because of the lack of universal enzymes to release them and the large background abundances of N-glycans.
32039582	1	35	from	Proteins	190:197	arg1	membrane					207:214	cell membrane	202:214	cell membrane	202:214	Proteins on cell membrane are modified by N- and O-glycans.
32039582	9	36	theme	cell	1413:1416	arg1	isomers					1436:1442	44 cell membrane O-glycan isomers	1410:1442	44 cell membrane O-glycan isomers with MS/MS	1410:1453	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	6	37	theme	degraded	916:923	arg1	proteins					925:932	degraded proteins	916:932	degraded proteins	916:932	Released O-glycans were purified by an optimized protocol to eliminate interference from small molecules and degraded proteins.
32039582	9	38	theme	O-glycan	1427:1434	arg1	isomers					1436:1442	44 cell membrane O-glycan isomers	1410:1442	44 cell membrane O-glycan isomers with MS/MS	1410:1453	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	11	39	theme	cell	1919:1922	arg1	differentiation					1924:1938	cell differentiation	1919:1938	cell differentiation	1919:1938	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	0	40	theme	O-Linked	45:52	arg1	Glycans					54:60	O-Linked Glycans	45:60	O-Linked Glycans on Cell Membrane	45:77	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	11	41	theme	changes	1904:1910	arg1	quantification					1795:1808	quantification	1795:1808	quantification	1795:1808	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	11	41	theme	changes	1904:1910	arg1	identification					1776:1789	identification	1776:1789	identification	1776:1789	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	11	41	theme	changes	1904:1910	arg1	study					1877:1881	the study	1873:1881	the study of specific O-glycan changes during cell differentiation	1873:1938	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	4	42	theme	human	603:607	arg1	membrane					614:621	human cell membrane	603:621	human cell membrane	603:621	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	0	43	theme	Differentiation	173:187	arg1	Type					154:157	Cell Type	149:157	Cell Type	149:157	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	0	43	theme	Differentiation	173:187	arg1	Stages					163:168	Stages	163:168	Stages of Differentiation	163:187	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	7	44	theme	surface	940:946	arg1	O-glycans					948:956	Cell surface O-glycans	935:956	Cell surface O-glycans	935:956	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	5	45	theme	cell	673:676	arg1	glycoproteins					687:699	isolated cell membrane glycoproteins	664:699	isolated cell membrane glycoproteins	664:699	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	6	46	theme	optimized	846:854	arg1	protocol					856:863	an optimized protocol to eliminate interference from small molecules and degraded proteins	843:932	an optimized protocol to eliminate interference from small molecules and degraded proteins	843:932	Released O-glycans were purified by an optimized protocol to eliminate interference from small molecules and degraded proteins.
32039582	11	47	dep	identification	1776:1789	arg1	the					1772:1774	the	1772:1774	the	1772:1774	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	3	48	theme	N-glycans	491:499	arg1	lack					410:413	the lack	406:413	the lack of universal enzymes to release them	406:450	However, O-glycans remain a challenge, because of the lack of universal enzymes to release them and the large background abundances of N-glycans.
32039582	3	48	theme	N-glycans	491:499	arg1	abundances					477:486	the large background abundances	456:486	the large background abundances of N-glycans	456:499	However, O-glycans remain a challenge, because of the lack of universal enzymes to release them and the large background abundances of N-glycans.
32039582	9	49	with	isomers	1436:1442	arg1	MS/MS					1449:1453	MS/MS	1449:1453	MS/MS	1449:1453	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	7	50	theme	reported	1193:1200	arg1	methods					1202:1208	previously reported methods	1182:1208	previously reported methods	1182:1208	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	11	51	from	lines	1863:1867	arg1	O-glycans					1833:1841	unique cell surface O-glycans	1813:1841	unique cell surface O-glycans from different cell lines	1813:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	11	51	from	lines	1863:1867	arg1	quantification					1795:1808	quantification	1795:1808	quantification	1795:1808	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	11	51	from	lines	1863:1867	arg1	identification					1776:1789	identification	1776:1789	identification	1776:1789	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	11	51	from	lines	1863:1867	arg1	study					1877:1881	the study	1873:1881	the study of specific O-glycan changes during cell differentiation	1873:1938	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	8	52	theme	exoglycosidase	1301:1314	arg1	digestion					1316:1324	exoglycosidase digestion	1301:1324	exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS)	1301:1374	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	6	53	from	molecules	902:910	arg1	interference					878:889	interference	878:889	interference from small molecules and degraded proteins	878:932	Released O-glycans were purified by an optimized protocol to eliminate interference from small molecules and degraded proteins.
32039582	7	54	theme	cell	1126:1129	arg1	fractions					1140:1148	the same cell membrane fractions	1117:1148	the same cell membrane fractions	1117:1148	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	2	55	theme	mass	326:329	arg1	techniques					344:353	advanced separation and mass spectrometry techniques	302:353	techniques	344:353	N-Glycans have been extensively characterized using advanced separation and mass spectrometry techniques.
32039582	9	56	theme	O-glycan	1507:1514	arg1	structures					1516:1525	25 O-glycan structures	1504:1525	25 O-glycan structures with exoglycosidase digestion	1504:1555	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	5	57	theme	lipid/glycolipid	724:739	arg1	removal					741:747	N-glycan and lipid/glycolipid removal	711:747	removal	741:747	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	6	58	theme	Released	807:814	arg1	O-glycans					816:824	Released O-glycans	807:824	Released O-glycans	807:824	Released O-glycans were purified by an optimized protocol to eliminate interference from small molecules and degraded proteins.
32039582	8	59	theme	tandem	1343:1348	arg1	MS/MS					1369:1373	MS/MS	1369:1373	MS/MS	1369:1373	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	8	59	theme	tandem	1343:1348	arg1	spectrometry					1355:1366	tandem mass spectrometry	1343:1366	tandem mass spectrometry (MS/MS)	1343:1374	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	10	60	theme	unexpected	1696:1705	arg1	oligomers					1715:1723	unexpected mannose oligomers	1696:1723	unexpected mannose oligomers that are α(1-2/3) linked	1696:1748	In this process, we identified and characterized unexpected mannose oligomers that are α(1-2/3) linked.
32039582	8	61	theme	O-glycans	1272:1280	arg1	linkages					1247:1254	linkages	1247:1254	linkages	1247:1254	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	8	61	theme	O-glycans	1272:1280	arg1	compositions					1230:1241	The monosaccharide compositions	1211:1241	The monosaccharide compositions	1211:1241	The monosaccharide compositions and linkages of the detected O-glycans were identified by exoglycosidase digestion facilitated with tandem mass spectrometry (MS/MS).
32039582	7	62	with	spectrometer	1007:1018	arg1	column					1059:1064	a porous graphitized carbon (PGC) column	1025:1064	a porous graphitized carbon (PGC) column	1025:1064	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	11	63	theme	O-glycan	1895:1902	arg1	changes					1904:1910	specific O-glycan changes	1886:1910	specific O-glycan changes during cell differentiation	1886:1938	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	5	64	theme	N-glycan	711:718	arg1	removal					741:747	N-glycan and lipid/glycolipid removal	711:747	removal	741:747	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	11	65	theme	cell	1820:1823	arg1	O-glycans					1833:1841	unique cell surface O-glycans	1813:1841	unique cell surface O-glycans from different cell lines	1813:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	0	66	theme	Cell	65:68	arg1	Membrane					70:77	Cell Membrane	65:77	Cell Membrane	65:77	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	4	67	attach	derived	590:596	arg1	membrane					614:621	human cell membrane	603:621	human cell membrane	603:621	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	4	67	attach	derived	590:596	arg2	O-glycans					580:588	O-glycans	580:588	O-glycans derived from human cell membrane	580:621	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	7	68	theme	PGC	1054:1056	arg1	column					1059:1064	a porous graphitized carbon (PGC) column	1025:1064	a porous graphitized carbon (PGC) column	1025:1064	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	5	69	gly	glycoproteins	687:699	arg1	glycoproteins					687:699	isolated cell membrane glycoproteins	664:699	isolated cell membrane glycoproteins	664:699	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	7	70	theme	carbon	1046:1051	arg1	column					1059:1064	a porous graphitized carbon (PGC) column	1025:1064	a porous graphitized carbon (PGC) column	1025:1064	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	0	71	theme	Glycomic	115:122	arg1	Profiles					124:131	Distinct Glycomic Profiles	106:131	Distinct Glycomic Profiles	106:131	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	5	72	attach	released	650:657	arg2	O-Glycans					624:632	O-Glycans	624:632	O-Glycans	624:632	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	5	72	attach	released	650:657	arg1	glycoproteins					687:699	isolated cell membrane glycoproteins	664:699	isolated cell membrane glycoproteins	664:699	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	11	73	theme	different	1848:1856	arg1	lines					1863:1867	different cell lines	1848:1867	different cell lines	1848:1867	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	5	74	theme	F	759:759	arg1	digestion					761:769	PNGase F digestion	752:769	PNGase F digestion	752:769	O-Glycans were chemically released from isolated cell membrane glycoproteins following N-glycan and lipid/glycolipid removal by PNGase F digestion and Folch extraction, respectively.
32039582	7	75	theme	porous	1027:1032	arg1	column					1059:1064	a porous graphitized carbon (PGC) column	1025:1064	a porous graphitized carbon (PGC) column	1025:1064	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	9	76	theme	accurate	1609:1616	arg1	masses					1618:1623	accurate masses	1609:1623	accurate masses	1609:1623	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	0	77	from	Glycans	54:60	arg1	Membrane					70:77	Cell Membrane	65:77	Cell Membrane	65:77	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	11	78	theme	O-glycans	1833:1841	arg1	quantification					1795:1808	quantification	1795:1808	quantification	1795:1808	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	11	78	theme	O-glycans	1833:1841	arg1	identification					1776:1789	identification	1776:1789	identification	1776:1789	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	11	78	theme	O-glycans	1833:1841	arg1	study					1877:1881	the study	1873:1881	the study of specific O-glycan changes during cell differentiation	1873:1938	This library enabled the identification and quantification of unique cell surface O-glycans from different cell lines and the study of specific O-glycan changes during cell differentiation.
32039582	0	79	theme	Distinct	106:113	arg1	Profiles					124:131	Distinct Glycomic Profiles	106:131	Distinct Glycomic Profiles	106:131	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	9	80	theme	exoglycosidase	1532:1545	arg1	digestion					1547:1555	exoglycosidase digestion	1532:1555	exoglycosidase digestion	1532:1555	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	0	81	theme	Structural	5:14	arg1	Analysis					16:23	Deep Structural Analysis	0:23	Deep Structural Analysis	0:23	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	7	82	theme	mass	1002:1005	arg1	spectrometer					1007:1018	a nanoLC-chip-QTOF mass spectrometer	983:1018	a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column	983:1064	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
32039582	9	83	theme	retention	1630:1638	arg1	times					1640:1644	retention times	1630:1644	retention times	1630:1644	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	10	84	theme	mannose	1707:1713	arg1	oligomers					1715:1723	unexpected mannose oligomers	1696:1723	unexpected mannose oligomers that are α(1-2/3) linked	1696:1748	In this process, we identified and characterized unexpected mannose oligomers that are α(1-2/3) linked.
32039582	3	85	theme	background	466:475	arg1	abundances					477:486	the large background abundances	456:486	the large background abundances of N-glycans	456:499	However, O-glycans remain a challenge, because of the lack of universal enzymes to release them and the large background abundances of N-glycans.
32039582	9	86	theme	membrane	1418:1425	arg1	isomers					1436:1442	44 cell membrane O-glycan isomers	1410:1442	44 cell membrane O-glycan isomers with MS/MS	1410:1453	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	3	87	theme	universal	418:426	arg1	enzymes					428:434	universal enzymes	418:434	universal enzymes	418:434	However, O-glycans remain a challenge, because of the lack of universal enzymes to release them and the large background abundances of N-glycans.
32039582	0	88	theme	Glycans	54:60	arg1	Analysis					16:23	Deep Structural Analysis	0:23	Deep Structural Analysis	0:23	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	0	88	theme	Glycans	54:60	arg1	Quantitation					29:40	Quantitation	29:40	Quantitation	29:40	Deep Structural Analysis and Quantitation of O-Linked Glycans on Cell Membrane Reveal High Abundances and Distinct Glycomic Profiles Associated with Cell Type and Stages of Differentiation.
32039582	6	89	theme	small	896:900	arg1	molecules					902:910	small molecules	896:910	small molecules	896:910	Released O-glycans were purified by an optimized protocol to eliminate interference from small molecules and degraded proteins.
32039582	4	90	theme	in-depth	531:538	arg1	analysis					551:558	in-depth structural analysis	531:558	in-depth structural analysis	531:558	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	9	91	with	structures	1516:1525	arg1	digestion					1547:1555	exoglycosidase digestion	1532:1555	exoglycosidase digestion	1532:1555	Using this method, we identified 44 cell membrane O-glycan isomers with MS/MS, and, among them, we unambiguously characterized 25 O-glycan structures with exoglycosidase digestion to create a library with their complete structures, accurate masses, and retention times.
32039582	4	92	theme	cell	609:612	arg1	membrane					614:621	human cell membrane	603:621	human cell membrane	603:621	Here, we report a method for in-depth structural analysis and quantitation of O-glycans derived from human cell membrane.
32039582	2	93	theme	spectrometry	331:342	arg1	techniques					344:353	advanced separation and mass spectrometry techniques	302:353	techniques	344:353	N-Glycans have been extensively characterized using advanced separation and mass spectrometry techniques.
32039582	7	94	theme	Cell	935:938	arg1	O-glycans					948:956	Cell surface O-glycans	935:956	Cell surface O-glycans	935:956	Cell surface O-glycans were then analyzed using a nanoLC-chip-QTOF mass spectrometer with a porous graphitized carbon (PGC) column, while the N-glycans and glycolipids isolated from the same cell membrane fractions were analyzed in parallel using previously reported methods.
34115468	1	0	theme	energy	162:167	arg1	storage					169:175	energy storage	162:175	energy storage	162:175	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	5	1	theme	solvent	915:921	arg1	control					923:929	solvent control	915:929	solvent control	915:929	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	1	2	dep	abundant	93:100	arg1	's					85:86	's	85:86	's	85:86	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	5	3	theme	linear	992:997	arg1	polymers					1021:1028	linear and branched α-glucan polymers	992:1028	linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	992:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	4	4	link	trans-linked	620:631	arg1	analogues					641:649	trans-linked glycans analogues	620:649	trans-linked glycans analogues of cellulose	620:662	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	2	5	theme	glucose	285:291	arg1	cellulose					257:265	cellulose	257:265	cellulose	257:265	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	5	theme	glucose	285:291	arg1	polymer					293:299	a β (1-4) linked glucose polymer	268:299	a β (1-4) linked glucose polymer	268:299	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	5	6	theme	branched	1003:1010	arg1	polymers					1021:1028	linear and branched α-glucan polymers	992:1028	linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	992:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	4	7	theme	Automated	569:577	arg1	Assembly					586:593	Automated Glycan Assembly	569:593	Automated Glycan Assembly	569:593	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	5	8	with	concert	886:892	arg1	temperature					899:909	temperature	899:909	temperature	899:909	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	5	8	with	concert	886:892	arg1	control					923:929	solvent control	915:929	solvent control	915:929	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	2	9	theme	linked	278:283	arg1	cellulose					257:265	cellulose	257:265	cellulose	257:265	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	9	theme	linked	278:283	arg1	polymer					293:299	a β (1-4) linked glucose polymer	268:299	a β (1-4) linked glucose polymer	268:299	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	4	10	theme	cis-glycosidic	714:727	arg1	linkages					729:736	multiple cis-glycosidic linkages	705:736	multiple cis-glycosidic linkages present in amylose	705:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	4	11	theme	stereoselective	673:687	arg1	installation					689:700	the stereoselective installation	669:700	the stereoselective installation of multiple cis-glycosidic linkages present in amylose	669:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	4	11	theme	stereoselective	673:687	arg1	possible					770:777	possible	770:777	possible	770:777	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	4	12	theme	multiple	705:712	arg1	linkages					729:736	multiple cis-glycosidic linkages	705:736	multiple cis-glycosidic linkages present in amylose	705:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	3	13	attach	isolated	538:545	arg1	sources					560:566	natural sources	552:566	natural sources	552:566	A detailed understanding of polysaccharide structures requires pure materials that cannot be isolated from natural sources.
34115468	3	13	attach	isolated	538:545	arg2	materials					513:521	pure materials	508:521	pure materials that cannot be isolated from natural sources	508:566	A detailed understanding of polysaccharide structures requires pure materials that cannot be isolated from natural sources.
34115468	5	14	theme	group	862:866	arg1	patterns					868:875	different protecting group patterns	841:875	different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	841:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	2	15	theme	energy	429:434	arg1	storage					436:442	energy storage	429:442	energy storage	429:442	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	16	theme	soft	401:404	arg1	fibers					413:418	soft hollow fibers	401:418	soft hollow fibers used for energy storage	401:442	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	6	17	theme	new	1101:1103	arg1	method					1105:1110	the new method	1097:1110	the new method	1097:1110	The molecules prepared with the new method will serve as probes to understand the biosynthesis and the structure of α-glucans.
34115468	2	18	theme	α	364:364	arg1	polymer					387:393	an α (1-4) linked glucose polymer	361:393	an α (1-4) linked glucose polymer	361:393	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	18	theme	α	364:364	arg1	amylose					352:358	amylose	352:358	amylose	352:358	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	19	theme	hollow	406:411	arg1	fibers					413:418	soft hollow fibers	401:418	soft hollow fibers used for energy storage	401:442	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	4	20	from	amylose	749:755	arg1	present					738:744	present	738:744	present	738:744	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	0	21	theme	Automated	0:8	arg1	Assembly					10:17	Automated Assembly	0:17	Automated Assembly of Starch and Glycogen Polysaccharides.	0:57	Automated Assembly of Starch and Glycogen Polysaccharides.
34115468	1	22	theme	abundant	93:100	arg1	Polysaccharides					59:73	Polysaccharides	59:73	Polysaccharides	59:73	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	1	22	theme	abundant	93:100	arg1	biomaterials					102:113	Nature's most abundant biomaterials	79:113	Nature's most abundant biomaterials essential for plant cell wall construction and energy storage	79:175	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	4	23	theme	cellulose	654:662	arg1	analogues					641:649	trans-linked glycans analogues	620:649	trans-linked glycans analogues of cellulose	620:662	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	0	24	theme	Starch	22:27	arg1	Assembly					10:17	Automated Assembly	0:17	Automated Assembly of Starch and Glycogen Polysaccharides.	0:57	Automated Assembly of Starch and Glycogen Polysaccharides.
34115468	5	25	theme	different	841:849	arg1	patterns					868:875	different protecting group patterns	841:875	different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	841:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	4	26	from	present	738:744	arg1	amylose					749:755	amylose	749:755	amylose	749:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	2	27	theme	glucose	379:385	arg1	polymer					387:393	an α (1-4) linked glucose polymer	361:393	an α (1-4) linked glucose polymer	361:393	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	27	theme	glucose	379:385	arg1	amylose					352:358	amylose	352:358	amylose	352:358	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	4	28	theme	present	738:744	arg1	linkages					729:736	multiple cis-glycosidic linkages	705:736	multiple cis-glycosidic linkages present in amylose	705:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	5	29	theme	excellent	940:948	arg1	stereoselectivity					950:966	excellent stereoselectivity	940:966	excellent stereoselectivity	940:966	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	2	30	theme	structural	194:203	arg1	differences					205:215	Seemingly minor structural differences	178:215	Seemingly minor structural differences	178:215	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	1	31	theme	essential	115:123	arg1	Polysaccharides					59:73	Polysaccharides	59:73	Polysaccharides	59:73	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	1	31	theme	essential	115:123	arg1	biomaterials					102:113	Nature's most abundant biomaterials	79:113	Nature's most abundant biomaterials essential for plant cell wall construction and energy storage	79:175	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	2	32	theme	linked	372:377	arg1	polymer					387:393	an α (1-4) linked glucose polymer	361:393	an α (1-4) linked glucose polymer	361:393	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	32	theme	linked	372:377	arg1	amylose					352:358	amylose	352:358	amylose	352:358	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	0	33	theme	Glycogen	33:40	arg1	Assembly					10:17	Automated Assembly	0:17	Automated Assembly of Starch and Glycogen Polysaccharides.	0:57	Automated Assembly of Starch and Glycogen Polysaccharides.
34115468	2	34	link	linked	278:283	arg1	cellulose					257:265	cellulose	257:265	cellulose	257:265	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	34	link	linked	278:283	arg1	polymer					293:299	a β (1-4) linked glucose polymer	268:299	a β (1-4) linked glucose polymer	268:299	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	5	35	with	blocks	829:834	arg1	patterns					868:875	different protecting group patterns	841:875	different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	841:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	2	36	theme	minor	188:192	arg1	differences					205:215	Seemingly minor structural differences	178:215	Seemingly minor structural differences	178:215	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	4	37	theme	glycans	633:639	arg1	analogues					641:649	trans-linked glycans analogues	620:649	trans-linked glycans analogues of cellulose	620:662	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	4	38	attach	present	738:744	arg2	linkages					729:736	multiple cis-glycosidic linkages	705:736	multiple cis-glycosidic linkages present in amylose	705:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	4	38	attach	present	738:744	arg1	amylose					749:755	amylose	749:755	amylose	749:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	5	39	theme	thioglycoside	806:818	arg1	blocks					829:834	thioglycoside building blocks	806:834	thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	806:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	5	40	theme	protecting	851:860	arg1	patterns					868:875	different protecting group patterns	841:875	different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	841:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	4	41	theme	trans-linked	620:631	arg1	analogues					641:649	trans-linked glycans analogues	620:649	trans-linked glycans analogues of cellulose	620:662	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	3	42	theme	natural	552:558	arg1	sources					560:566	natural sources	552:566	natural sources	552:566	A detailed understanding of polysaccharide structures requires pure materials that cannot be isolated from natural sources.
34115468	2	43	theme	large	333:337	arg1	trees					339:343	large trees	333:343	large trees	333:343	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	6	44	theme	α-glucans	1185:1193	arg1	biosynthesis					1151:1162	the biosynthesis	1147:1162	the biosynthesis	1147:1162	The molecules prepared with the new method will serve as probes to understand the biosynthesis and the structure of α-glucans.
34115468	6	44	theme	α-glucans	1185:1193	arg1	structure					1172:1180	the structure	1168:1180	the structure	1168:1180	The molecules prepared with the new method will serve as probes to understand the biosynthesis and the structure of α-glucans.
34115468	5	45	theme	cis-glycosidic	1044:1057	arg1	linkages					1059:1066	up to 20 cis-glycosidic linkages	1035:1066	up to 20 cis-glycosidic linkages	1035:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	2	46	theme	different	236:244	arg1	functions					246:254	entirely different functions	227:254	entirely different functions	227:254	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	1	47	theme	plant	129:133	arg1	construction					145:156	plant cell wall construction	129:156	plant cell wall construction	129:156	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	4	48	theme	linkages	729:736	arg1	installation					689:700	the stereoselective installation	669:700	the stereoselective installation of multiple cis-glycosidic linkages present in amylose	669:755	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	4	48	theme	linkages	729:736	arg1	possible					770:777	possible	770:777	possible	770:777	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	5	49	theme	polymers	1021:1028	arg1	synthesis					979:987	the synthesis	975:987	the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	975:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	0	50	dep	Starch	22:27	arg1	Polysaccharides					42:56	Polysaccharides	42:56	Polysaccharides	42:56	Automated Assembly of Starch and Glycogen Polysaccharides.
34115468	1	51	theme	cell	135:138	arg1	construction					145:156	plant cell wall construction	129:156	plant cell wall construction	129:156	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	3	52	theme	pure	508:511	arg1	materials					513:521	pure materials	508:521	pure materials that cannot be isolated from natural sources	508:566	A detailed understanding of polysaccharide structures requires pure materials that cannot be isolated from natural sources.
34115468	2	53	theme	β	270:270	arg1	cellulose					257:265	cellulose	257:265	cellulose	257:265	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	53	theme	β	270:270	arg1	polymer					293:299	a β (1-4) linked glucose polymer	268:299	a β (1-4) linked glucose polymer	268:299	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	1	54	theme	wall	140:143	arg1	construction					145:156	plant cell wall construction	129:156	plant cell wall construction	129:156	Polysaccharides are Nature's most abundant biomaterials essential for plant cell wall construction and energy storage.
34115468	4	55	theme	Glycan	579:584	arg1	Assembly					586:593	Automated Glycan Assembly	569:593	Automated Glycan Assembly	569:593	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	2	56	link	linked	372:377	arg1	polymer					387:393	an α (1-4) linked glucose polymer	361:393	an α (1-4) linked glucose polymer	361:393	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	2	56	link	linked	372:377	arg1	amylose					352:358	amylose	352:358	amylose	352:358	Seemingly minor structural differences result in entirely different functions: cellulose, a β (1-4) linked glucose polymer, forms fibrils that can support large trees, while amylose, an α (1-4) linked glucose polymer forms soft hollow fibers used for energy storage.
34115468	5	57	theme	α-glucan	1012:1019	arg1	polymers					1021:1028	linear and branched α-glucan polymers	992:1028	linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	992:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	3	58	theme	polysaccharide	473:486	arg1	structures					488:497	polysaccharide structures	473:497	polysaccharide structures	473:497	A detailed understanding of polysaccharide structures requires pure materials that cannot be isolated from natural sources.
34115468	5	59	dep	20	1041:1042	arg1	to					1038:1039	to	1038:1039	to	1038:1039	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	4	60	theme	quick	604:608	arg1	access					610:615	quick access	604:615	quick access to trans-linked glycans analogues of cellulose	604:662	Automated Glycan Assembly provides quick access to trans-linked glycans analogues of cellulose, but the stereoselective installation of multiple cis-glycosidic linkages present in amylose has not been possible to date.
34115468	5	61	with	polymers	1021:1028	arg1	linkages					1059:1066	up to 20 cis-glycosidic linkages	1035:1066	up to 20 cis-glycosidic linkages	1035:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	5	62	theme	building	820:827	arg1	blocks					829:834	thioglycoside building blocks	806:834	thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages	806:1066	Here, we identify thioglycoside building blocks with different protecting group patterns that, in concert with temperature and solvent control, achieve excellent stereoselectivity during the synthesis of linear and branched α-glucan polymers with up to 20 cis-glycosidic linkages.
34115468	3	63	theme	structures	488:497	arg1	understanding					456:468	A detailed understanding	445:468	A detailed understanding of polysaccharide structures	445:497	A detailed understanding of polysaccharide structures requires pure materials that cannot be isolated from natural sources.
34115468	3	64	theme	detailed	447:454	arg1	understanding					456:468	A detailed understanding	445:468	A detailed understanding of polysaccharide structures	445:497	A detailed understanding of polysaccharide structures requires pure materials that cannot be isolated from natural sources.
34023000	8	0	theme	charge	1279:1284	arg1	heterogeneity					1286:1298	the charge heterogeneity	1275:1298	the charge heterogeneity of the test compounds	1275:1320	Finally, capillary isoelectric focusing shed light on the charge heterogeneity of the test compounds, providing important complementary information.
34023000	5	1	theme	F	745:745	arg1	antibodies					756:765	PNGase F digested antibodies	738:765	PNGase F digested antibodies	738:765	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	1	2	theme	new	197:199	arg1	antibodies					221:230	two development phase new modality monoclonal antibodies	175:230	two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound	175:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	2	theme	new	197:199	arg1	glycoengineered					244:258	glycoengineered	244:258	glycoengineered	244:258	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	2	theme	new	197:199	arg1	compound					282:289	a bispecific test compound	264:289	a bispecific test compound	264:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	2	3	from	intact	357:362	arg1	characterization					333:348	multilevel characterization	322:348	multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels	322:453	The samples were subjected to multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels.
34023000	5	4	theme	antibodies	756:765	arg1	Separation					724:733	Separation	724:733	Separation of PNGase F digested antibodies	724:765	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	7	5	theme	gel	1079:1081	arg1	electrophoresis					1083:1097	capillary gel electrophoresis	1069:1097	capillary gel electrophoresis	1069:1097	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	6	6	theme	efficient	884:892	arg1	removal					901:907	efficient glycan removal	884:907	efficient glycan removal	884:907	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	1	7	theme	modality	201:208	arg1	antibodies					221:230	two development phase new modality monoclonal antibodies	175:230	two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound	175:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	7	theme	modality	201:208	arg1	glycoengineered					244:258	glycoengineered	244:258	glycoengineered	244:258	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	7	theme	modality	201:208	arg1	compound					282:289	a bispecific test compound	264:289	a bispecific test compound	264:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	4	8	theme	temperature	617:627	arg1	gradient					629:636	a special temperature gradient denaturation process and a	607:663	gradient	629:636	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	5	9	theme	time	786:789	arg1	shifts					791:796	migration time shifts	776:796	migration time shifts	776:796	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	6	10	theme	glycan	894:899	arg1	removal					901:907	efficient glycan removal	884:907	efficient glycan removal	884:907	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	8	11	theme	compounds	1312:1320	arg1	heterogeneity					1286:1298	the charge heterogeneity	1275:1298	the charge heterogeneity of the test compounds	1275:1320	Finally, capillary isoelectric focusing shed light on the charge heterogeneity of the test compounds, providing important complementary information.
34023000	4	12	theme	chain	707:711	arg1	fragments					713:721	two light chain fragments	697:721	its two light chain fragments	693:721	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	3	13	theme	heavy	544:548	arg1	chains					550:555	the light and heavy chains	530:555	chains	550:555	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	4	14	theme	denaturation	638:649	arg1	process					651:657	denaturation process	638:657	denaturation process	638:657	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	8	15	theme	test	1307:1310	arg1	compounds					1312:1320	the test compounds	1303:1320	the test compounds	1303:1320	Finally, capillary isoelectric focusing shed light on the charge heterogeneity of the test compounds, providing important complementary information.
34023000	1	16	theme	Capillary	86:94	arg1	methods					122:128	Capillary gel electrophoresis-based methods	86:128	Capillary gel electrophoresis-based methods	86:128	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	17	theme	monoclonal	210:219	arg1	antibodies					221:230	two development phase new modality monoclonal antibodies	175:230	two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound	175:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	17	theme	monoclonal	210:219	arg1	glycoengineered					244:258	glycoengineered	244:258	glycoengineered	244:258	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	17	theme	monoclonal	210:219	arg1	compound					282:289	a bispecific test compound	264:289	a bispecific test compound	264:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	5	18	theme	corresponding	856:868	arg1	subunits					870:877	the corresponding subunits	852:877	the corresponding subunits	852:877	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	7	19	theme	carbohydrate	1196:1207	arg1	sequencing					1209:1218	exoglycosidase based carbohydrate sequencing	1175:1218	exoglycosidase based carbohydrate sequencing	1175:1218	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	2	20	theme	multilevel	322:331	arg1	characterization					333:348	multilevel characterization	322:348	multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels	322:453	The samples were subjected to multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels.
34023000	3	21	theme	electrophoresis	474:488	arg1	analysis					490:497	SDS capillary gel electrophoresis analysis	456:497	SDS capillary gel electrophoresis analysis	456:497	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	0	22	theme	capillary	11:19	arg1	electrophoresis					25:39	Multilevel capillary gel electrophoresis	0:39	Multilevel capillary gel electrophoresis characterization of new antibody modalities.	0:84	Multilevel capillary gel electrophoresis characterization of new antibody modalities.
34023000	5	23	theme	N-linked	826:833	arg1	glycosylation					835:847	N-linked glycosylation	826:847	N-linked glycosylation	826:847	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	7	24	theme	released	1035:1042	arg1	glycans					1044:1050	The released glycans	1031:1050	The released glycans	1031:1050	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	1	25	theme	electrophoresis-based	100:120	arg1	methods					122:128	Capillary gel electrophoresis-based methods	86:128	Capillary gel electrophoresis-based methods	86:128	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	3	26	theme	SDS	456:458	arg1	electrophoresis					474:488	SDS capillary gel electrophoresis	456:488	SDS capillary gel electrophoresis analysis	456:497	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	0	27	theme	Multilevel	0:9	arg1	electrophoresis					25:39	Multilevel capillary gel electrophoresis	0:39	Multilevel capillary gel electrophoresis characterization of new antibody modalities.	0:84	Multilevel capillary gel electrophoresis characterization of new antibody modalities.
34023000	5	28	from	presence	814:821	arg1	subunits					870:877	the corresponding subunits	852:877	the corresponding subunits	852:877	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	7	29	theme	exoglycosidase	1175:1188	arg1	sequencing					1209:1218	exoglycosidase based carbohydrate sequencing	1175:1218	exoglycosidase based carbohydrate sequencing	1175:1218	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	2	30	dep	SDS-SGE	373:379	arg1	both					365:368	both	365:368	both	365:368	The samples were subjected to multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels.
34023000	2	31	theme	reduced	406:412	arg1	protein					414:420	the reduced protein	402:420	the reduced protein	402:420	The samples were subjected to multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels.
34023000	0	32	theme	electrophoresis	25:39	arg1	characterization					41:56	Multilevel capillary gel electrophoresis characterization	0:56	Multilevel capillary gel electrophoresis characterization of new antibody modalities.	0:84	Multilevel capillary gel electrophoresis characterization of new antibody modalities.
34023000	5	33	theme	digested	747:754	arg1	antibodies					756:765	PNGase F digested antibodies	738:765	PNGase F digested antibodies	738:765	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	3	34	theme	excellent	506:514	arg1	separation					516:525	excellent separation	506:525	excellent separation of the light and heavy chains of both samples	506:571	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	0	35	theme	gel	21:23	arg1	electrophoresis					25:39	Multilevel capillary gel electrophoresis	0:39	Multilevel capillary gel electrophoresis characterization of new antibody modalities.	0:84	Multilevel capillary gel electrophoresis characterization of new antibody modalities.
34023000	4	36	theme	special	609:615	arg1	gradient					629:636	a special temperature gradient denaturation process and a	607:663	gradient	629:636	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	3	37	theme	samples	565:571	arg1	chains					550:555	the light and heavy chains	530:555	chains	550:555	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	6	38	theme	monoclonal	950:959	arg1	antibody					961:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	6	38	theme	monoclonal	950:959	arg1	digested					982:989	digested	982:989	digested	982:989	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	3	39	theme	chains	550:555	arg1	separation					516:525	excellent separation	506:525	excellent separation of the light and heavy chains of both samples	506:571	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	5	40	theme	glycosylation	835:847	arg1	presence					814:821	the presence	810:821	the presence of N-linked glycosylation on the corresponding subunits	810:877	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	6	41	theme	glycoengineered	934:948	arg1	antibody					961:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	6	41	theme	glycoengineered	934:948	arg1	digested					982:989	digested	982:989	digested	982:989	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	3	42	theme	capillary	460:468	arg1	electrophoresis					474:488	SDS capillary gel electrophoresis	456:488	SDS capillary gel electrophoresis analysis	456:497	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	2	43	theme	N-glycan	439:446	arg1	levels					448:453	the released N-glycan levels	426:453	the released N-glycan levels	426:453	The samples were subjected to multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels.
34023000	3	44	theme	gel	470:472	arg1	electrophoresis					474:488	SDS capillary gel electrophoresis	456:488	SDS capillary gel electrophoresis analysis	456:497	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	6	45	gly	glycosylated	921:932	arg1	antibody					961:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	6	45	gly	glycosylated	921:932	arg1	digested					982:989	digested	982:989	digested	982:989	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	5	46	theme	migration	776:784	arg1	shifts					791:796	migration time shifts	776:796	migration time shifts	776:796	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	4	47	dep	gradient	629:636	arg1	process					651:657	denaturation process	638:657	denaturation process	638:657	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	8	48	theme	important	1333:1341	arg1	information					1357:1367	important complementary information	1333:1367	important complementary information	1333:1367	Finally, capillary isoelectric focusing shed light on the charge heterogeneity of the test compounds, providing important complementary information.
34023000	2	49	from	protein	414:420	arg1	characterization					333:348	multilevel characterization	322:348	multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels	322:453	The samples were subjected to multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels.
34023000	1	50	theme	bispecific	266:275	arg1	compound					282:289	a bispecific test compound	264:289	a bispecific test compound	264:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	0	51	theme	antibody	65:72	arg1	modalities					74:83	new antibody modalities	61:83	new antibody modalities	61:83	Multilevel capillary gel electrophoresis characterization of new antibody modalities.
34023000	7	52	theme	based	1190:1194	arg1	sequencing					1209:1218	exoglycosidase based carbohydrate sequencing	1175:1218	exoglycosidase based carbohydrate sequencing	1175:1218	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	8	53	theme	complementary	1343:1355	arg1	information					1357:1367	important complementary information	1333:1367	important complementary information	1333:1367	Finally, capillary isoelectric focusing shed light on the charge heterogeneity of the test compounds, providing important complementary information.
34023000	7	54	theme	oligosaccharide	1129:1143	arg1	structures					1145:1154	their oligosaccharide structures	1123:1154	their oligosaccharide structures	1123:1154	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	3	55	theme	light	534:538	arg1	chains					550:555	the light and heavy chains	530:555	chains	550:555	SDS capillary gel electrophoresis analysis showed excellent separation of the light and heavy chains of both samples.
34023000	0	56	theme	new	61:63	arg1	modalities					74:83	new antibody modalities	61:83	new antibody modalities	61:83	Multilevel capillary gel electrophoresis characterization of new antibody modalities.
34023000	4	57	theme	bispecific	578:587	arg1	antibody					589:596	The bispecific antibody	574:596	The bispecific antibody	574:596	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	5	58	link	N-linked	826:833	arg1	glycosylation					835:847	N-linked glycosylation	826:847	N-linked glycosylation	826:847	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	9	59	theme	workflow	1402:1409	arg1	optimization					1411:1422	workflow optimization	1402:1422	workflow optimization	1402:1422	A flowchart was established for workflow optimization.
34023000	7	60	theme	APTS	1105:1108	arg1	labeling					1110:1117	APTS labeling	1105:1117	APTS labeling	1105:1117	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	6	61	theme	glycosylated	921:932	arg1	antibody					961:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	the highly glycosylated glycoengineered monoclonal antibody	910:968	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	6	61	theme	glycosylated	921:932	arg1	digested					982:989	digested	982:989	digested	982:989	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	5	62	theme	PNGase	738:743	arg1	antibodies					756:765	PNGase F digested antibodies	738:765	PNGase F digested antibodies	738:765	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	1	63	theme	test	277:280	arg1	compound					282:289	a bispecific test compound	264:289	a bispecific test compound	264:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	64	theme	gel	96:98	arg1	methods					122:128	Capillary gel electrophoresis-based methods	86:128	Capillary gel electrophoresis-based methods	86:128	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	5	65	attach	presence	814:821	arg2	glycosylation					835:847	N-linked glycosylation	826:847	N-linked glycosylation	826:847	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	5	65	attach	presence	814:821	arg1	subunits					870:877	the corresponding subunits	852:877	the corresponding subunits	852:877	Separation of PNGase F digested antibodies revealed migration time shifts, suggesting the presence of N-linked glycosylation on the corresponding subunits.
34023000	8	66	gly	heterogeneity	1286:1298	arg1	compounds					1312:1320	the test compounds	1303:1320	the test compounds	1303:1320	Finally, capillary isoelectric focusing shed light on the charge heterogeneity of the test compounds, providing important complementary information.
34023000	2	67	theme	released	430:437	arg1	levels					448:453	the released N-glycan levels	426:453	the released N-glycan levels	426:453	The samples were subjected to multilevel characterization at the intact (both by SDS-SGE and cIEF) as well as the reduced protein and the released N-glycan levels.
34023000	1	68	theme	development	179:189	arg1	antibodies					221:230	two development phase new modality monoclonal antibodies	175:230	two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound	175:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	68	theme	development	179:189	arg1	glycoengineered					244:258	glycoengineered	244:258	glycoengineered	244:258	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	68	theme	development	179:189	arg1	compound					282:289	a bispecific test compound	264:289	a bispecific test compound	264:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	4	69	theme	light	701:705	arg1	fragments					713:721	two light chain fragments	697:721	its two light chain fragments	693:721	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	4	70	theme	capillary	672:680	arg1	gradient					629:636	a special temperature gradient denaturation process and a	607:663	gradient	629:636	The bispecific antibody required a special temperature gradient denaturation process and a longer capillary to resolve its two light chain fragments.
34023000	0	71	theme	modalities	74:83	arg1	characterization					41:56	Multilevel capillary gel electrophoresis characterization	0:56	Multilevel capillary gel electrophoresis characterization of new antibody modalities.	0:84	Multilevel capillary gel electrophoresis characterization of new antibody modalities.
34023000	6	72	theme	endoglycosidase	1004:1018	arg1	treatment					1020:1028	the endoglycosidase treatment	1000:1028	the endoglycosidase treatment	1000:1028	For efficient glycan removal, the highly glycosylated glycoengineered monoclonal antibody was trypsin digested prior to the endoglycosidase treatment.
34023000	7	73	theme	capillary	1069:1077	arg1	electrophoresis					1083:1097	capillary gel electrophoresis	1069:1097	capillary gel electrophoresis	1069:1097	The released glycans were profiled by capillary gel electrophoresis after APTS labeling and their oligosaccharide structures were identified by exoglycosidase based carbohydrate sequencing.
34023000	1	74	theme	phase	191:195	arg1	antibodies					221:230	two development phase new modality monoclonal antibodies	175:230	two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound	175:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	74	theme	phase	191:195	arg1	glycoengineered					244:258	glycoengineered	244:258	glycoengineered	244:258	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
34023000	1	74	theme	phase	191:195	arg1	compound					282:289	a bispecific test compound	264:289	a bispecific test compound	264:289	Capillary gel electrophoresis-based methods were applied to comprehensively characterize two development phase new modality monoclonal antibodies including a glycoengineered and a bispecific test compound.
31826991	12	0	theme	glycan	1658:1663	arg1	subtype					1665:1671	glycan subtype	1658:1671	glycan subtype	1658:1671	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	15	1	theme	strains	2561:2567	arg1	hemagglutinins					2537:2550	the hemagglutinins	2533:2550	the hemagglutinins of LPAIV strains	2533:2567	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	4	2	theme	region	527:532	arg1	glycosites					547:556	head region high-mannose glycosites	522:556	head region high-mannose glycosites	522:556	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	11	3	theme	glycan	1506:1511	arg1	presence					1481:1488	the presence	1477:1488	the presence of high-mannose glycan on the head region	1477:1530	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	4	4	gly	glycosite	611:619	arg2	glycosite					611:619	these glycosite glycan subtypes	605:635	these glycosite glycan subtypes	605:635	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	9	5	theme	H3	1334:1335	arg1	HA					1337:1338	H3 HA	1334:1338	H3 HA	1334:1338	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	12	6	theme	pandemic	1897:1904	arg1	viruses					1906:1912	pandemic viruses	1897:1912	pandemic viruses	1897:1912	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	0	7	from	Subtypes	111:118	arg1	Interactions					137:148	Host-Pathogen Interactions	123:148	Host-Pathogen Interactions	123:148	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	1	8	attach	removed	241:247	arg2	sites					228:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	8	attach	removed	241:247	arg1	lung					258:261	the lung	254:261	the lung	254:261	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	13	9	with	interaction	2203:2213	arg1	hemagglutinin					2220:2232	hemagglutinin	2220:2232	hemagglutinin	2220:2232	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	4	10	theme	glycosite	611:619	arg1	subtypes					628:635	these glycosite glycan subtypes	605:635	these glycosite glycan subtypes	605:635	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	3	11	theme	human	481:485	arg1	populations					487:497	human populations	481:497	human populations	481:497	These can pose a pandemic threat through reassortment and emergence in human populations.
31826991	9	12	theme	complex	1347:1353	arg1	glycans					1355:1361	complex glycans	1347:1361	complex glycans in all LPAIV HAs	1347:1378	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	12	13	theme	circulating	1867:1877	arg1	strains					1885:1891	circulating human strains	1867:1891	circulating human strains	1867:1891	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	11	14	contain	containing	1594:1603	arg2	subtypes					1614:1621	these HA subtypes	1605:1621	these HA subtypes	1605:1621	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	11	14	contain	containing	1594:1603	arg1	virus					1588:1592	virus	1588:1592	virus containing these HA subtypes	1588:1621	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	0	15	theme	N-Glycan	102:109	arg1	Subtypes					111:118	N-Glycan Subtypes	102:118	N-Glycan Subtypes in Host-Pathogen Interactions	102:148	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	8	16	theme	glycosite	1179:1187	arg1	glycan					1189:1194	glycosite glycan	1179:1194	glycosite glycan	1179:1194	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	13	17	theme	type	2176:2179	arg1	HA					2235:2236	HA	2235:2236	HA	2235:2236	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	17	theme	type	2176:2179	arg1	IAV					2190:2192	IAV	2190:2192	IAV	2190:2192	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	17	theme	type	2176:2179	arg1	virus					2183:2187	influenza type A virus	2166:2187	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	18	from	factor	2112:2117	arg1	defense					2149:2155	first-line innate immunity defense	2122:2155	first-line innate immunity defense	2122:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	1	19	theme	influenza	160:168	arg1	HA					198:199	HA	198:199	HA	198:199	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	19	theme	influenza	160:168	arg1	hemagglutinin					183:195	Seasonal influenza carrying key hemagglutinin	151:195	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	15	20	theme	high-mannose	2594:2605	arg1	glycans					2607:2613	the required high-mannose glycans	2581:2613	the required high-mannose glycans	2581:2613	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	7	21	theme	structure	996:1004	arg1	analysis					1006:1013	molecular structure analysis	986:1013	molecular structure analysis	986:1013	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	1	22	theme	key	179:181	arg1	HA					198:199	HA	198:199	HA	198:199	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	22	theme	key	179:181	arg1	hemagglutinin					183:195	Seasonal influenza carrying key hemagglutinin	151:195	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	14	23	theme	similar	2404:2410	arg1	glycosylation					2412:2424	similar glycosylation	2404:2424	similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks	2404:2504	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	8	24	theme	available	1205:1213	arg1	data					1243:1246	available three-dimensional structure data	1205:1246	available three-dimensional structure data	1205:1246	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	0	25	theme	D	99:99	arg1	Targets					59:65	Targets	59:65	Targets of Pulmonary Surfactant Protein D	59:99	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	7	26	theme	LPAIV	1045:1049	arg1	strains					1051:1057	LPAIV strains	1045:1057	LPAIV strains	1045:1057	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	14	27	dep	H3	2310:2311	arg1	HAs					2313:2315	HAs	2313:2315	HAs	2313:2315	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	8	28	theme	structure	1233:1241	arg1	data					1243:1246	available three-dimensional structure data	1205:1246	available three-dimensional structure data	1205:1246	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	7	29	theme	Sequence	963:970	arg1	alignment					972:980	Sequence alignment	963:980	Sequence alignment	963:980	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	5	30	theme	human	820:824	arg1	subtype					840:846	a human seasonal H3N2 subtype	818:846	a human seasonal H3N2 subtype	818:846	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	13	31	theme	head	2239:2242	arg1	s					2271:2271	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	11	32	theme	HA	1611:1612	arg1	subtypes					1614:1621	these HA subtypes	1605:1621	these HA subtypes	1605:1621	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	15	33	theme	LPAIV	2555:2559	arg1	strains					2561:2567	LPAIV strains	2555:2567	LPAIV strains	2555:2567	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	5	34	theme	H3N2	835:838	arg1	subtype					840:846	a human seasonal H3N2 subtype	818:846	a human seasonal H3N2 subtype	818:846	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	13	35	theme	first-line	2122:2131	arg1	defense					2149:2155	first-line innate immunity defense	2122:2155	first-line innate immunity defense	2122:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	5	36	theme	recombinant	697:707	arg1	forms					720:724	two recombinant human SP-D forms	693:724	two recombinant human SP-D forms	693:724	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	9	37	gly	glycosite	1263:1271	arg2	glycosite					1263:1271	glycosite	1263:1271	glycosite	1263:1271	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	5	38	theme	SP-D	715:718	arg1	forms					720:724	two recombinant human SP-D forms	693:724	two recombinant human SP-D forms	693:724	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	12	39	theme	influenza	1816:1824	arg1	virus					1826:1830	structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus	1761:1830	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	12	39	theme	influenza	1816:1824	arg1	LPAIV					1833:1837	LPAIV	1833:1837	LPAIV	1833:1837	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	13	40	theme	key	2108:2110	arg1	D					2096:2096	Lung surfactant protein D	2072:2096	Lung surfactant protein D (SP-D)	2072:2103	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	40	theme	key	2108:2110	arg1	factor					2112:2117	a key factor	2106:2117	a key factor in first-line innate immunity defense	2106:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	12	41	theme	H2	1993:1994	arg1	virus					1996:2000	an H2 virus	1990:2000	an H2 virus reassorted with the circulating H1N1	1990:2037	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	13	42	theme	glycan	2264:2269	arg1	s					2271:2271	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	43	theme	innate	2133:2138	arg1	defense					2149:2155	first-line innate immunity defense	2122:2155	first-line innate immunity defense	2122:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	12	44	theme	structural	1761:1770	arg1	virus					1826:1830	structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus	1761:1830	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	12	44	theme	structural	1761:1770	arg1	LPAIV					1833:1837	LPAIV	1833:1837	LPAIV	1833:1837	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	14	45	theme	health	2493:2498	arg1	risks					2500:2504	future health risks	2486:2504	future health risks	2486:2504	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	2	46	theme	HA	327:328	arg1	glycosylation					335:347	HA head glycosylation	327:347	HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes	327:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	0	47	theme	Influenza	0:8	arg1	Hemagglutinins					16:29	Influenza Virus Hemagglutinins H2, H5, H6, and H11	0:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11	0:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	47	theme	Influenza	0:8	arg1	H5					35:36	H5	35:36	H5	35:36	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	47	theme	Influenza	0:8	arg1	H2					31:32	H2	31:32	H2	31:32	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	47	theme	Influenza	0:8	arg1	H11					47:49	H11	47:49	H11	47:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	47	theme	Influenza	0:8	arg1	H6					39:40	H6	39:40	H6	39:40	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	13	48	theme	protein	2088:2094	arg1	D					2096:2096	Lung surfactant protein D	2072:2096	Lung surfactant protein D (SP-D)	2072:2103	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	48	theme	protein	2088:2094	arg1	factor					2112:2117	a key factor	2106:2117	a key factor in first-line innate immunity defense	2106:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	48	theme	protein	2088:2094	arg1	SP-D					2099:2102	SP-D	2099:2102	SP-D	2099:2102	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	12	49	theme	Low-pathogenicity	1792:1808	arg1	virus					1826:1830	structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus	1761:1830	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	12	49	theme	Low-pathogenicity	1792:1808	arg1	LPAIV					1833:1837	LPAIV	1833:1837	LPAIV	1833:1837	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	12	50	gly	glycosites	1698:1707	arg2	glycosites					1698:1707	some glycosites	1693:1707	some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1693:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	2	51	theme	influenza	376:384	arg1	LPAIV					393:397	LPAIV	393:397	LPAIV	393:397	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	2	51	theme	influenza	376:384	arg1	virus					386:390	avian influenza virus	370:390	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	12	52	theme	sequence	1718:1725	arg1	comparisons					1727:1737	sequence comparisons	1718:1737	sequence comparisons	1718:1737	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	13	53	theme	region	2244:2249	arg1	s					2271:2271	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	6	54	gly	glycosylation	943:955	arg2	site					957:960	each head glycosylation site	933:960	each head glycosylation site	933:960	Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site.
31826991	7	55	theme	avian	1094:1098	arg1	H3N8					1100:1103	avian H3N8	1094:1103	avian H3N8	1094:1103	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	14	56	contain	have	2317:2320	arg1	H3					2310:2311	H3 HAs	2310:2315	H3 HAs	2310:2315	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	56	contain	have	2317:2320	arg1	H1					2303:2304	H1	2303:2304	H1	2303:2304	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	56	contain	have	2317:2320	arg2	glycosites					2351:2360	one or more key high-mannose glycosites	2322:2360	one or more key high-mannose glycosites	2322:2360	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	57	gly	glycosylation	2412:2424	arg1	H6N1					2455:2458	H6N1	2455:2458	H6N1	2455:2458	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	57	gly	glycosylation	2412:2424	arg1	strains					2435:2441	LPAIV strains	2429:2441	LPAIV strains	2429:2441	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	57	gly	glycosylation	2412:2424	arg1	H5N1					2449:2452	H5N1	2449:2452	H5N1	2449:2452	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	57	gly	glycosylation	2412:2424	arg1	H2N1					2443:2446	H2N1	2443:2446	H2N1	2443:2446	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	57	gly	glycosylation	2412:2424	arg1	H11N9					2464:2468	H11N9	2464:2468	H11N9	2464:2468	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	2	58	theme	low-pathogenicity	352:368	arg1	subtypes					400:407	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	9	59	theme	H3	1281:1282	arg1	"					1278:1278	glycosite "N165"	1263:1278	glycosite "N165" (H3 numbering)	1263:1293	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	9	59	theme	H3	1281:1282	arg1	numbering					1284:1292	H3 numbering	1281:1292	H3 numbering	1281:1292	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	15	60	dep	presence	2721:2728	arg1	the					2717:2719	the	2717:2719	the	2717:2719	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	6	61	theme	glycosylation	943:955	arg1	site					957:960	each head glycosylation site	933:960	each head glycosylation site	933:960	Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site.
31826991	12	62	theme	H2N2	2057:2060	arg1	genotype					2062:2069	a novel H2N2 genotype	2049:2069	a novel H2N2 genotype	2049:2069	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	3	63	theme	pandemic	427:434	arg1	threat					436:441	a pandemic threat	425:441	a pandemic threat	425:441	These can pose a pandemic threat through reassortment and emergence in human populations.
31826991	5	64	theme	LPAIV	749:753	arg1	H5N1					780:783	H5N1	780:783	H5N1	780:783	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	64	theme	LPAIV	749:753	arg1	H6N1					786:789	H6N1	786:789	H6N1	786:789	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	64	theme	LPAIV	749:753	arg1	H3N8					808:811	an avian H3N8	799:811	an avian H3N8	799:811	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	64	theme	LPAIV	749:753	arg1	strains					755:761	representative LPAIV strains	734:761	representative LPAIV strains	734:761	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	64	theme	LPAIV	749:753	arg1	subtype					840:846	a human seasonal H3N2 subtype	818:846	a human seasonal H3N2 subtype	818:846	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	64	theme	LPAIV	749:753	arg1	H2N1					774:777	H2N1	774:777	H2N1	774:777	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	64	theme	LPAIV	749:753	arg1	H11N9					792:796	H11N9	792:796	H11N9	792:796	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	1	65	theme	surfactant	276:285	arg1	SP-D					298:301	SP-D	298:301	SP-D	298:301	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	65	theme	surfactant	276:285	arg1	D					295:295	pulmonary surfactant protein D	266:295	pulmonary surfactant protein D (SP-D)	266:302	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	9	66	from	glycans	1323:1329	arg1	HA					1337:1338	H3 HA	1334:1338	H3 HA	1334:1338	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	12	67	theme	circulating	2022:2032	arg1	H1N1					2034:2037	the circulating H1N1	2018:2037	the circulating H1N1	2018:2037	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	0	68	dep	Hemagglutinins	16:29	arg1	H11					47:49	H11	47:49	H11	47:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	68	dep	Hemagglutinins	16:29	arg1	H5					35:36	H5	35:36	H5	35:36	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	68	dep	Hemagglutinins	16:29	arg1	H2					31:32	H2	31:32	H2	31:32	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	68	dep	Hemagglutinins	16:29	arg1	Hemagglutinins					16:29	Influenza Virus Hemagglutinins H2, H5, H6, and H11	0:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11	0:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	68	dep	Hemagglutinins	16:29	arg1	H6					39:40	H6	39:40	H6	39:40	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	9	69	from	glycans	1355:1361	arg1	LPAIV					1370:1374	all LPAIV	1366:1374	all LPAIV HAs	1366:1378	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	11	70	theme	high-mannose	1493:1504	arg1	glycan					1506:1511	high-mannose glycan	1493:1511	high-mannose glycan	1493:1511	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	11	71	from	presence	1481:1488	arg1	region					1525:1530	the head region	1516:1530	the head region	1516:1530	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	9	72	theme	high-mannose	1310:1321	arg1	glycans					1323:1329	high-mannose glycans	1310:1329	high-mannose glycans in H3 HA	1310:1338	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	15	73	theme	marker	2759:2764	arg1	presence					2721:2728	presence	2721:2728	presence	2721:2728	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	15	73	theme	marker	2759:2764	arg1	absence					2733:2739	absence	2733:2739	absence	2733:2739	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	11	74	theme	head	1520:1523	arg1	region					1525:1530	the head region	1516:1530	the head region	1516:1530	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	1	75	theme	glycosylation	214:226	arg1	sites					228:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	12	76	theme	human	1928:1932	arg1	populations					1934:1944	human populations	1928:1944	human populations	1928:1944	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	14	77	theme	strains	2435:2441	arg1	glycosylation					2412:2424	similar glycosylation	2404:2424	similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks	2404:2504	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	4	78	theme	head	522:525	arg1	glycosites					547:556	head region high-mannose glycosites	522:556	head region high-mannose glycosites	522:556	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	4	79	theme	high-mannose	534:545	arg1	glycosites					547:556	head region high-mannose glycosites	522:556	head region high-mannose glycosites	522:556	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	7	80	theme	the	1018:1020	arg1	analysis					1006:1013	molecular structure analysis	986:1013	molecular structure analysis	986:1013	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	7	80	theme	the	1018:1020	arg1	alignment					972:980	Sequence alignment	963:980	Sequence alignment	963:980	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	13	81	theme	A	2181:2181	arg1	HA					2235:2236	HA	2235:2236	HA	2235:2236	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	81	theme	A	2181:2181	arg1	IAV					2190:2192	IAV	2190:2192	IAV	2190:2192	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	81	theme	A	2181:2181	arg1	virus					2183:2187	influenza type A virus	2166:2187	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	82	theme	influenza	2166:2174	arg1	HA					2235:2236	HA	2235:2236	HA	2235:2236	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	82	theme	influenza	2166:2174	arg1	IAV					2190:2192	IAV	2190:2192	IAV	2190:2192	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	82	theme	influenza	2166:2174	arg1	virus					2183:2187	influenza type A virus	2166:2187	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	9	83	used	occupied	1298:1305	arg2	numbering					1284:1292	H3 numbering	1281:1292	H3 numbering	1281:1292	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	9	83	used	occupied	1298:1305	arg2	"					1278:1278	glycosite "N165"	1263:1278	glycosite "N165" (H3 numbering)	1263:1293	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	13	84	theme	Lung	2072:2075	arg1	D					2096:2096	Lung surfactant protein D	2072:2096	Lung surfactant protein D (SP-D)	2072:2103	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	84	theme	Lung	2072:2075	arg1	factor					2112:2117	a key factor	2106:2117	a key factor in first-line innate immunity defense	2106:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	84	theme	Lung	2072:2075	arg1	SP-D					2099:2102	SP-D	2099:2102	SP-D	2099:2102	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	8	85	theme	protein	1158:1164	arg1	backbone					1166:1173	protein backbone	1158:1173	protein backbone	1158:1173	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	1	86	theme	Seasonal	151:158	arg1	HA					198:199	HA	198:199	HA	198:199	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	86	theme	Seasonal	151:158	arg1	hemagglutinin					183:195	Seasonal influenza carrying key hemagglutinin	151:195	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	14	87	theme	LPAIV	2429:2433	arg1	H6N1					2455:2458	H6N1	2455:2458	H6N1	2455:2458	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	87	theme	LPAIV	2429:2433	arg1	strains					2435:2441	LPAIV strains	2429:2441	LPAIV strains	2429:2441	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	87	theme	LPAIV	2429:2433	arg1	H5N1					2449:2452	H5N1	2449:2452	H5N1	2449:2452	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	87	theme	LPAIV	2429:2433	arg1	H2N1					2443:2446	H2N1	2443:2446	H2N1	2443:2446	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	87	theme	LPAIV	2429:2433	arg1	H11N9					2464:2468	H11N9	2464:2468	H11N9	2464:2468	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	4	88	theme	glycan	621:626	arg1	subtypes					628:635	these glycosite glycan subtypes	605:635	these glycosite glycan subtypes	605:635	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	7	89	theme	molecular	986:994	arg1	analysis					1006:1013	molecular structure analysis	986:1013	molecular structure analysis	986:1013	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	11	90	theme	SP-D	1435:1438	arg1	affinity					1440:1447	SP-D affinity	1435:1447	SP-D affinity for influenza HA	1435:1464	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	1	91	theme	carrying	170:177	arg1	HA					198:199	HA	198:199	HA	198:199	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	91	theme	carrying	170:177	arg1	hemagglutinin					183:195	Seasonal influenza carrying key hemagglutinin	151:195	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	8	92	theme	Intramolecular	1106:1119	arg1	contacts					1121:1128	Intramolecular contacts	1106:1128	Intramolecular contacts	1106:1128	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	13	93	theme	virus	2183:2187	arg1	s					2271:2271	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	1	94	theme	hemagglutinin	183:195	arg1	sites					228:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	6	95	theme	mass	855:858	arg1	spectrometry					860:871	mass spectrometry	855:871	mass spectrometry	855:871	Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site.
31826991	15	96	theme	glycan	2685:2690	arg1	subtype					2692:2698	glycan subtype	2685:2698	glycan subtype	2685:2698	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	13	97	theme	surfactant	2077:2086	arg1	D					2096:2096	Lung surfactant protein D	2072:2096	Lung surfactant protein D (SP-D)	2072:2103	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	97	theme	surfactant	2077:2086	arg1	factor					2112:2117	a key factor	2106:2117	a key factor in first-line innate immunity defense	2106:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	13	97	theme	surfactant	2077:2086	arg1	SP-D					2099:2102	SP-D	2099:2102	SP-D	2099:2102	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	7	98	dep	the	1018:1020	arg1	HAs					1022:1024	HAs	1022:1024	HAs	1022:1024	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	10	99	dep	H3	1421:1422	arg1	HAs					1424:1426	HAs	1424:1426	HAs	1424:1426	SP-D was not active on LPAIV but was on H3 HAs.
31826991	8	100	gly	glycosite	1179:1187	arg2	glycosite					1179:1187	glycosite glycan	1179:1194	glycosite glycan	1179:1194	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	0	101	theme	Protein	91:97	arg1	D					99:99	Pulmonary Surfactant Protein D	70:99	Pulmonary Surfactant Protein D	70:99	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	4	102	theme	glycosites	547:556	arg1	presence					510:517	the presence	506:517	the presence of head region high-mannose glycosites	506:556	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	8	103	theme	three-dimensional	1215:1231	arg1	data					1243:1246	available three-dimensional structure data	1205:1246	available three-dimensional structure data	1205:1246	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	14	104	gly	glycosites	2351:2360	arg2	glycosites					2351:2360	one or more key high-mannose glycosites	2322:2360	one or more key high-mannose glycosites	2322:2360	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	0	105	theme	Host-Pathogen	123:135	arg1	Interactions					137:148	Host-Pathogen Interactions	123:148	Host-Pathogen Interactions	123:148	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	5	106	theme	seasonal	826:833	arg1	subtype					840:846	a human seasonal H3N2 subtype	818:846	a human seasonal H3N2 subtype	818:846	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	6	107	theme	head	938:941	arg1	site					957:960	each head glycosylation site	933:960	each head glycosylation site	933:960	Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site.
31826991	15	108	theme	sequence	2655:2662	arg1	analysis					2664:2671	sequence analysis	2655:2671	sequence analysis	2655:2671	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	12	109	theme	1957	1966:1969	arg1	pandemic					1971:1978	the 1957 pandemic	1962:1978	the 1957 pandemic	1962:1978	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	13	110	theme	immunity	2140:2147	arg1	defense					2149:2155	first-line innate immunity defense	2122:2155	first-line innate immunity defense	2122:2155	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	5	111	theme	avian	802:806	arg1	H3N8					808:811	an avian H3N8	799:811	an avian H3N8	799:811	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	14	112	theme	head	2369:2372	arg1	region					2374:2379	the head region	2365:2379	the head region	2365:2379	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	113	theme	high-mannose	2338:2349	arg1	glycosites					2351:2360	one or more key high-mannose glycosites	2322:2360	one or more key high-mannose glycosites	2322:2360	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	12	114	theme	human	1879:1883	arg1	strains					1885:1891	circulating human strains	1867:1891	circulating human strains	1867:1891	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	5	115	theme	human	709:713	arg1	forms					720:724	two recombinant human SP-D forms	693:724	two recombinant human SP-D forms	693:724	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	12	116	theme	virus	1826:1830	arg1	subtypes					1840:1847	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	0	117	theme	Surfactant	80:89	arg1	D					99:99	Pulmonary Surfactant Protein D	70:99	Pulmonary Surfactant Protein D	70:99	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	13	118	theme	high-mannose	2251:2262	arg1	s					2271:2271	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s)	2166:2272	Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s).
31826991	6	119	theme	glycan	892:897	arg1	subclasses					899:908	subclasses	899:908	subclasses	899:908	Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site.
31826991	15	120	theme	required	2585:2592	arg1	glycans					2607:2613	the required high-mannose glycans	2581:2613	the required high-mannose glycans	2581:2613	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	0	121	theme	Pulmonary	70:78	arg1	D					99:99	Pulmonary Surfactant Protein D	70:99	Pulmonary Surfactant Protein D	70:99	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	12	122	theme	analysis.IMPORTANCE	1772:1790	arg1	virus					1826:1830	structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus	1761:1830	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	12	122	theme	analysis.IMPORTANCE	1772:1790	arg1	LPAIV					1833:1837	LPAIV	1833:1837	LPAIV	1833:1837	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	0	123	dep	Targets	59:65	arg1	Subtypes					111:118	N-Glycan Subtypes	102:118	N-Glycan Subtypes in Host-Pathogen Interactions	102:148	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	14	124	theme	key	2334:2336	arg1	glycosites					2351:2360	one or more key high-mannose glycosites	2322:2360	one or more key high-mannose glycosites	2322:2360	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	2	125	gly	glycosylation	335:347	arg1	subtypes					400:407	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	2	126	theme	head	330:333	arg1	glycosylation					335:347	HA head glycosylation	327:347	HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes	327:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	0	127	theme	Virus	10:14	arg1	Hemagglutinins					16:29	Influenza Virus Hemagglutinins H2, H5, H6, and H11	0:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11	0:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	127	theme	Virus	10:14	arg1	H5					35:36	H5	35:36	H5	35:36	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	127	theme	Virus	10:14	arg1	H2					31:32	H2	31:32	H2	31:32	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	127	theme	Virus	10:14	arg1	H11					47:49	H11	47:49	H11	47:49	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	0	127	theme	Virus	10:14	arg1	H6					39:40	H6	39:40	H6	39:40	Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions.
31826991	9	128	theme	glycosite	1263:1271	arg1	"					1278:1278	glycosite "N165"	1263:1278	glycosite "N165" (H3 numbering)	1263:1293	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	9	128	theme	glycosite	1263:1271	arg1	numbering					1284:1292	H3 numbering	1281:1292	H3 numbering	1281:1292	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	12	129	theme	avian	1810:1814	arg1	virus					1826:1830	structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus	1761:1830	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	12	129	theme	avian	1810:1814	arg1	LPAIV					1833:1837	LPAIV	1833:1837	LPAIV	1833:1837	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	1	130	gly	glycosylation	214:226	arg2	sites					228:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	14	131	dep	strains	2435:2441	arg1	strains					2435:2441	LPAIV strains	2429:2441	LPAIV strains	2429:2441	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	131	dep	strains	2435:2441	arg1	H6N1					2455:2458	H6N1	2455:2458	H6N1	2455:2458	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	131	dep	strains	2435:2441	arg1	H11N9					2464:2468	H11N9	2464:2468	H11N9	2464:2468	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	131	dep	strains	2435:2441	arg1	H5N1					2449:2452	H5N1	2449:2452	H5N1	2449:2452	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	131	dep	strains	2435:2441	arg1	H2N1					2443:2446	H2N1	2443:2446	H2N1	2443:2446	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	14	132	theme	future	2486:2491	arg1	risks					2500:2504	future health risks	2486:2504	future health risks	2486:2504	While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks.
31826991	15	133	contain	have	2576:2579	arg2	glycans					2607:2613	the required high-mannose glycans	2581:2613	the required high-mannose glycans	2581:2613	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	15	133	contain	have	2576:2579	arg1	hemagglutinins					2537:2550	the hemagglutinins	2533:2550	the hemagglutinins of LPAIV strains	2533:2567	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	7	134	theme	seasonal	1076:1083	arg1	H3N2					1085:1088	seasonal H3N2	1076:1088	seasonal H3N2	1076:1088	Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8.
31826991	9	135	theme	N165	1274:1277	arg1	"					1278:1278	glycosite "N165"	1263:1278	glycosite "N165" (H3 numbering)	1263:1293	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	9	135	theme	N165	1274:1277	arg1	numbering					1284:1292	H3 numbering	1281:1292	H3 numbering	1281:1292	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	4	136	gly	glycosites	547:556	arg2	glycosites					547:556	head region high-mannose glycosites	522:556	head region high-mannose glycosites	522:556	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	8	137	dep	backbone	1166:1173	arg1	the					1154:1156	the	1154:1156	the	1154:1156	Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data.
31826991	2	138	theme	virus	386:390	arg1	subtypes					400:407	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	2	139	theme	avian	370:374	arg1	LPAIV					393:397	LPAIV	393:397	LPAIV	393:397	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	2	139	theme	avian	370:374	arg1	virus					386:390	avian influenza virus	370:390	low-pathogenicity avian influenza virus (LPAIV) subtypes	352:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	5	140	theme	forms	720:724	arg1	activities					679:688	the activities	675:688	the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype	675:846	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	12	141	theme	three-dimensional	1743:1759	arg1	subtypes					1840:1847	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes	1743:1847	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	1	142	theme	head	202:205	arg1	sites					228:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	5	143	theme	representative	734:747	arg1	H5N1					780:783	H5N1	780:783	H5N1	780:783	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	143	theme	representative	734:747	arg1	H6N1					786:789	H6N1	786:789	H6N1	786:789	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	143	theme	representative	734:747	arg1	H3N8					808:811	an avian H3N8	799:811	an avian H3N8	799:811	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	143	theme	representative	734:747	arg1	strains					755:761	representative LPAIV strains	734:761	representative LPAIV strains	734:761	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	143	theme	representative	734:747	arg1	subtype					840:846	a human seasonal H3N2 subtype	818:846	a human seasonal H3N2 subtype	818:846	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	143	theme	representative	734:747	arg1	H2N1					774:777	H2N1	774:777	H2N1	774:777	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	5	143	theme	representative	734:747	arg1	H11N9					792:796	H11N9	792:796	H11N9	792:796	Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype.
31826991	1	144	theme	pulmonary	266:274	arg1	SP-D					298:301	SP-D	298:301	SP-D	298:301	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	144	theme	pulmonary	266:274	arg1	D					295:295	pulmonary surfactant protein D	266:295	pulmonary surfactant protein D (SP-D)	266:302	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	2	145	theme	subtypes	400:407	arg1	glycosylation					335:347	HA head glycosylation	327:347	HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes	327:407	Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes.
31826991	12	146	theme	novel	2051:2055	arg1	genotype					2062:2069	a novel H2N2 genotype	2049:2069	a novel H2N2 genotype	2049:2069	Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis.IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype.
31826991	11	147	theme	influenza	1453:1461	arg1	HA					1463:1464	influenza HA	1453:1464	influenza HA	1453:1464	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	1	148	theme	protein	287:293	arg1	SP-D					298:301	SP-D	298:301	SP-D	298:301	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	1	148	theme	protein	287:293	arg1	D					295:295	pulmonary surfactant protein D	266:295	pulmonary surfactant protein D (SP-D)	266:302	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
31826991	4	149	theme	SP-D	567:570	arg1	activity					572:579	SP-D activity	567:579	SP-D activity	567:579	Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value.
31826991	15	150	theme	virulence	2749:2757	arg1	marker					2759:2764	this virulence marker	2744:2764	this virulence marker	2744:2764	Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.
31826991	11	151	attach	presence	1481:1488	arg2	glycan					1506:1511	high-mannose glycan	1493:1511	high-mannose glycan	1493:1511	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	11	151	attach	presence	1481:1488	arg1	region					1525:1530	the head region	1516:1530	the head region	1516:1530	Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes.
31826991	9	152	dep	LPAIV	1370:1374	arg1	HAs					1376:1378	HAs	1376:1378	HAs	1376:1378	We found that glycosite "N165" (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs.
31826991	1	153	theme	region	207:212	arg1	sites					228:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites	151:232	Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D).
33516683	6	0	theme	mass	1107:1110	arg1	spectrometry					1134:1145	High mass accuracy imaging mass spectrometry	1102:1145	High mass accuracy imaging mass spectrometry (IMS)	1102:1151	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	6	0	theme	mass	1107:1110	arg1	IMS					1148:1150	IMS	1148:1150	IMS	1148:1150	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	1	1	theme	matrix	250:255	arg1	production					263:272	deregulated extracellular matrix (ECM) production	224:272	deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets	224:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	9	2	theme	diagnosed	1418:1426	arg1	tissue					1428:1433	AVI diagnosed tissue	1414:1433	AVI diagnosed tissue	1414:1433	In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures.
33516683	4	3	theme	congenital	849:858	arg1	stenosis					873:880	pediatric congenital aortic valve stenosis	839:880	pediatric congenital aortic valve stenosis	839:880	Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis.
33516683	12	4	theme	valve	1792:1796	arg1	sialylation					1805:1815	aortic valve tissue sialylation	1785:1815	aortic valve tissue sialylation	1785:1815	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	6	5	theme	N-glycan	1174:1181	arg1	profiles					1183:1190	N-glycan profiles	1174:1190	N-glycan profiles	1174:1190	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	11	6	theme	common	1669:1674	arg1	elevation					1676:1684	common elevation	1669:1684	common elevation in AS independent of age	1669:1709	Three sialylated N-glycans showed common elevation in AS independent of age.
33516683	13	7	theme	normal	1978:1983	arg1	fibrosa					1985:1991	the normal fibrosa	1974:1991	the normal fibrosa	1974:1991	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	6	8	used	used	1157:1160	arg2	IMS					1148:1150	IMS	1148:1150	IMS	1148:1150	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	6	8	used	used	1157:1160	arg2	spectrometry					1134:1145	High mass accuracy imaging mass spectrometry	1102:1145	High mass accuracy imaging mass spectrometry (IMS)	1102:1151	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	10	9	from	group	1628:1632	arg1	types					1541:1545	all valve types	1531:1545	all valve types	1531:1545	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	4	10	theme	valve	867:871	arg1	stenosis					873:880	pediatric congenital aortic valve stenosis	839:880	pediatric congenital aortic valve stenosis	839:880	Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis.
33516683	1	11	theme	obstructive	173:183	arg1	narrowing					185:193	an obstructive narrowing	170:193	an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets	170:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	14	12	theme	disease	2212:2218	arg1	treatment					2180:2188	the treatment	2176:2188	the treatment of human aortic valve disease	2176:2218	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	3	13	theme	valve	740:744	arg1	structure					746:754	the valve structure	736:754	the valve structure in disease	736:765	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	5	14	theme	pediatric	1079:1087	arg1	endstage					1089:1096	pediatric endstage	1079:1096	pediatric endstage	1079:1096	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	3	15	theme	all	541:543	arg1	glycoproteins					545:557	almost all glycoproteins	534:557	almost all glycoproteins clinically linked to stenotic valvular modeling	534:605	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	9	16	theme	hypertrophic	1459:1470	arg1	commissures					1472:1482	hypertrophic commissures	1459:1482	hypertrophic commissures	1459:1482	In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures.
33516683	11	17	gly	sialylated	1641:1650	arg1	N-glycans					1652:1660	Three sialylated N-glycans	1635:1660	Three sialylated N-glycans	1635:1660	Three sialylated N-glycans showed common elevation in AS independent of age.
33516683	14	18	theme	aortic	2199:2204	arg1	disease					2212:2218	human aortic valve disease	2193:2218	human aortic valve disease	2193:2218	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	3	19	theme	valvular	589:596	arg1	modeling					598:605	stenotic valvular modeling	580:605	stenotic valvular modeling	580:605	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	1	20	theme	aortic	202:207	arg1	orifice					209:215	the aortic orifice	198:215	the aortic orifice	198:215	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	10	21	theme	abundant	1610:1617	arg1	N-glycans					1586:1594	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	10	21	theme	abundant	1610:1617	arg1	group					1628:1632	the most abundant N-glycan group	1601:1632	the most abundant N-glycan group	1601:1632	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	1	22	theme	Congenital	118:127	arg1	stenosis					142:149	Congenital aortic valve stenosis	118:149	Congenital aortic valve stenosis (AS)	118:154	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	12	23	theme	chemical	1722:1729	arg1	methods					1731:1737	On-tissue chemical methods	1712:1737	On-tissue chemical methods optimized for valvular tissue	1712:1767	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	5	24	theme	age	936:938	arg1	0-17 years					922:931	0-17 years	922:931	valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS	905:1099	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	1	25	theme	aortic	129:134	arg1	stenosis					142:149	Congenital aortic valve stenosis	118:149	Congenital aortic valve stenosis (AS)	118:154	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	6	26	theme	AV	1199:1200	arg1	structure					1202:1210	the AV structure	1195:1210	the AV structure	1195:1210	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	2	27	theme	carbohydrate	449:460	arg1	content					462:468	valvular carbohydrate content	440:468	valvular carbohydrate content	440:468	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	13	28	theme	primary	1928:1934	arg1	configuration					1943:1955	the primary fucose configuration	1924:1955	the primary fucose configuration	1924:1955	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	13	28	theme	primary	1928:1934	arg1	fucosylation					1908:1919	core fucosylation	1903:1919	core fucosylation	1903:1919	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	0	29	theme	pediatric	65:73	arg1	stenosis					108:115	pediatric endstage congenital aortic valve stenosis	65:115	pediatric endstage congenital aortic valve stenosis	65:115	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	5	30	theme	valvular	905:912	arg1	tissues					914:920	valvular tissues	905:920	valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS	905:1099	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	8	31	theme	normal	1339:1344	arg1	valve					1353:1357	the normal aortic valve	1335:1357	the normal aortic valve	1335:1357	The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis.
33516683	0	32	theme	congenital	84:93	arg1	stenosis					108:115	pediatric endstage congenital aortic valve stenosis	65:115	pediatric endstage congenital aortic valve stenosis	65:115	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	1	33	theme	heart	317:321	arg1	failure					323:329	heart failure	317:329	heart failure with no effective therapies	317:357	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	7	34	used	used	1225:1228	arg2	RNA-Seq					1213:1219	RNA-Seq	1213:1219	RNA-Seq	1213:1219	RNA-Seq was used to identify regulation of N-glycan related enzymes.
33516683	5	35	theme	pre-operative	983:995	arg1	function					1003:1010	pre-operative valve function	983:1010	pre-operative valve function spanning normal development	983:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	1	36	theme	valve	136:140	arg1	stenosis					142:149	Congenital aortic valve stenosis	118:149	Congenital aortic valve stenosis (AS)	118:154	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	14	37	theme	research	2152:2159	arg1	directions					2161:2170	new research directions	2148:2170	new research directions for the treatment of human aortic valve disease	2148:2218	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	5	38	dep	tissues	914:920	arg1	0-17 years					922:931	0-17 years	922:931	valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS	905:1099	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	13	39	theme	core	1903:1906	arg1	configuration					1943:1955	the primary fucose configuration	1924:1955	the primary fucose configuration	1924:1955	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	13	39	theme	core	1903:1906	arg1	fucosylation					1908:1919	core fucosylation	1903:1919	core fucosylation	1903:1919	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	0	40	theme	valve	102:106	arg1	stenosis					108:115	pediatric endstage congenital aortic valve stenosis	65:115	pediatric endstage congenital aortic valve stenosis	65:115	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	14	41	theme	aortic	2063:2068	arg1	valve					2070:2074	human aortic valve	2057:2074	the human aortic valve structure	2053:2084	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	0	42	theme	Spatial	0:6	arg1	N-glycomics					8:18	Spatial N-glycomics	0:18	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.	0:116	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	5	43	theme	de-identified	945:957	arg1	data					968:971	de-identified clinical data	945:971	de-identified clinical data reporting pre-operative valve function spanning normal development	945:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	1	44	dep	stenosis	142:149	arg1	AS					152:153	AS	152:153	AS	152:153	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	13	45	theme	enzymatic	1864:1872	arg1	strategies					1874:1883	Specialized enzymatic strategies	1852:1883	Specialized enzymatic strategies	1852:1883	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	2	46	theme	proteoglycan	388:399	arg1	distribution					401:412	proteoglycan distribution	388:412	proteoglycan distribution	388:412	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	14	47	theme	N-glycomic	2110:2119	arg1	signaling					2121:2129	N-glycomic signaling	2110:2129	N-glycomic signaling	2110:2129	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	4	48	theme	N-glycan	812:819	arg1	structures					821:830	N-glycan structures	812:830	N-glycan structures	812:830	Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis.
33516683	5	49	with	endstage	1089:1096	arg1	data					968:971	de-identified clinical data	945:971	de-identified clinical data reporting pre-operative valve function spanning normal development	945:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	0	50	theme	human	27:31	arg1	valve					40:44	the human aortic valve	23:44	the human aortic valve	23:44	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	1	51	theme	valve	284:288	arg1	leaflets					295:302	aortic valve (AV) leaflets	277:302	aortic valve (AV) leaflets	277:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	5	52	theme	valve	1048:1052	arg1	AVI					1069:1071	AVI	1069:1071	AVI	1069:1071	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	5	52	theme	valve	1048:1052	arg1	insufficiency					1054:1066	aortic valve insufficiency	1041:1066	aortic valve insufficiency (AVI)	1041:1072	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	12	53	theme	α2,3	1837:1840	arg1	linkages					1842:1849	both α2,6 and α2,3 linkages	1823:1849	both α2,6 and α2,3 linkages	1823:1849	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	2	54	theme	AS	432:433	arg1	hallmark					420:427	a hallmark	418:427	a hallmark of AS	418:433	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	2	54	theme	AS	432:433	arg1	Changes					360:366	Changes	360:366	Changes in glycoprotein and proteoglycan distribution	360:412	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	10	55	theme	valve	1535:1539	arg1	types					1541:1545	all valve types	1531:1545	all valve types	1531:1545	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	0	56	theme	valve	40:44	arg1	N-glycomics					8:18	Spatial N-glycomics	0:18	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.	0:116	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	1	57	theme	AV	291:292	arg1	leaflets					295:302	aortic valve (AV) leaflets	277:302	aortic valve (AV) leaflets	277:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	2	58	from	Changes	360:366	arg1	glycoprotein					371:382	glycoprotein	371:382	glycoprotein	371:382	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	2	58	from	Changes	360:366	arg1	distribution					401:412	proteoglycan distribution	388:412	proteoglycan distribution	388:412	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	1	59	theme	orifice	209:215	arg1	narrowing					185:193	an obstructive narrowing	170:193	an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets	170:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	5	60	theme	normal	1021:1026	arg1	development					1028:1038	normal development	1021:1038	normal development	1021:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	7	61	theme	enzymes	1273:1279	arg1	regulation					1242:1251	regulation	1242:1251	regulation of N-glycan related enzymes	1242:1279	RNA-Seq was used to identify regulation of N-glycan related enzymes.
33516683	10	62	theme	acid	1555:1558	arg1	N-glycans					1586:1594	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	10	62	theme	acid	1555:1558	arg1	group					1628:1632	the most abundant N-glycan group	1601:1632	the most abundant N-glycan group	1601:1632	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	12	63	theme	α2,6	1828:1831	arg1	linkages					1842:1849	both α2,6 and α2,3 linkages	1823:1849	both α2,6 and α2,3 linkages	1823:1849	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	7	64	theme	N-glycan	1256:1263	arg1	enzymes					1273:1279	N-glycan related enzymes	1256:1279	N-glycan related enzymes	1256:1279	RNA-Seq was used to identify regulation of N-glycan related enzymes.
33516683	1	65	theme	extracellular	236:248	arg1	matrix					250:255	extracellular matrix	236:255	deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets	224:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	1	65	theme	extracellular	236:248	arg1	ECM					258:260	ECM	258:260	ECM	258:260	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	12	66	theme	aortic	1785:1790	arg1	sialylation					1805:1815	aortic valve tissue sialylation	1785:1815	aortic valve tissue sialylation	1785:1815	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	6	67	theme	High	1102:1105	arg1	spectrometry					1134:1145	High mass accuracy imaging mass spectrometry	1102:1145	High mass accuracy imaging mass spectrometry (IMS)	1102:1151	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	6	67	theme	High	1102:1105	arg1	IMS					1148:1150	IMS	1148:1150	IMS	1148:1150	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	5	68	with	insufficiency	1054:1066	arg1	data					968:971	de-identified clinical data	945:971	de-identified clinical data reporting pre-operative valve function spanning normal development	945:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	11	69	theme	sialylated	1641:1650	arg1	N-glycans					1652:1660	Three sialylated N-glycans	1635:1660	Three sialylated N-glycans	1635:1660	Three sialylated N-glycans showed common elevation in AS independent of age.
33516683	12	70	theme	tissue	1798:1803	arg1	sialylation					1805:1815	aortic valve tissue sialylation	1785:1815	aortic valve tissue sialylation	1785:1815	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	10	71	theme	N-acetylneuraminic	1561:1578	arg1	acid					1555:1558	sialic acid	1548:1558	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	10	71	theme	N-acetylneuraminic	1561:1578	arg1	acid					1580:1583	N-acetylneuraminic acid	1561:1583	N-acetylneuraminic acid	1561:1583	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	4	72	theme	pediatric	839:847	arg1	stenosis					873:880	pediatric congenital aortic valve stenosis	839:880	pediatric congenital aortic valve stenosis	839:880	Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis.
33516683	12	73	theme	valvular	1753:1760	arg1	tissue					1762:1767	valvular tissue	1753:1767	valvular tissue	1753:1767	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	4	74	theme	aortic	860:865	arg1	stenosis					873:880	pediatric congenital aortic valve stenosis	839:880	pediatric congenital aortic valve stenosis	839:880	Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis.
33516683	9	75	from	increases	1489:1497	arg1	structures					1516:1525	pauci-mannose structures	1502:1525	pauci-mannose structures	1502:1525	In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures.
33516683	4	76	theme	structures	821:830	arg1	localization					796:807	spatial localization	788:807	spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis	788:880	Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis.
33516683	14	77	theme	valve	2206:2210	arg1	disease					2212:2218	human aortic valve disease	2193:2218	human aortic valve disease	2193:2218	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	5	78	theme	endstage	1089:1096	arg1	0-17 years					922:931	0-17 years	922:931	valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS	905:1099	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	3	79	theme	stenotic	580:587	arg1	modeling					598:605	stenotic valvular modeling	580:605	stenotic valvular modeling	580:605	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	2	80	theme	molecular	511:519	arg1	level					521:525	the molecular level	507:525	the molecular level	507:525	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	10	81	theme	N-glycan	1619:1626	arg1	N-glycans					1586:1594	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	10	81	theme	N-glycan	1619:1626	arg1	group					1628:1632	the most abundant N-glycan group	1601:1632	the most abundant N-glycan group	1601:1632	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	3	82	gly	glycoproteins	545:557	arg1	glycoproteins					545:557	almost all glycoproteins	534:557	almost all glycoproteins clinically linked to stenotic valvular modeling	534:605	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	13	83	theme	disparate	1998:2006	arg1	patterning					2008:2017	disparate patterning	1998:2017	disparate patterning in AS	1998:2023	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	3	84	theme	multiple	615:622	arg1	sites					624:628	multiple sites	615:628	multiple sites for N-glycosylation	615:648	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	9	85	theme	pauci-mannose	1502:1514	arg1	structures					1516:1525	pauci-mannose structures	1502:1525	pauci-mannose structures	1502:1525	In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures.
33516683	12	86	theme	On-tissue	1712:1720	arg1	methods					1731:1737	On-tissue chemical methods	1712:1737	On-tissue chemical methods optimized for valvular tissue	1712:1767	On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages.
33516683	1	87	with	failure	323:329	arg1	therapies					349:357	no effective therapies	336:357	no effective therapies	336:357	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	2	88	from	level	521:525	arg1	uncharacterized					488:502	uncharacterized	488:502	uncharacterized	488:502	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	0	89	theme	endstage	75:82	arg1	stenosis					108:115	pediatric endstage congenital aortic valve stenosis	65:115	pediatric endstage congenital aortic valve stenosis	65:115	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	13	90	from	patterning	2008:2017	arg1	AS					2022:2023	AS	2022:2023	AS	2022:2023	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	2	91	theme	valvular	440:447	arg1	content					462:468	valvular carbohydrate content	440:468	valvular carbohydrate content	440:468	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	0	92	from	N-glycomics	8:18	arg1	development					49:59	development	49:59	development	49:59	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	0	92	from	N-glycomics	8:18	arg1	stenosis					108:115	pediatric endstage congenital aortic valve stenosis	65:115	pediatric endstage congenital aortic valve stenosis	65:115	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	13	93	theme	fucose	1936:1941	arg1	configuration					1943:1955	the primary fucose configuration	1924:1955	the primary fucose configuration	1924:1955	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	13	93	theme	fucose	1936:1941	arg1	fucosylation					1908:1919	core fucosylation	1903:1919	core fucosylation	1903:1919	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	1	94	theme	effective	339:347	arg1	therapies					349:357	no effective therapies	336:357	no effective therapies	336:357	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	0	95	theme	aortic	95:100	arg1	stenosis					108:115	pediatric endstage congenital aortic valve stenosis	65:115	pediatric endstage congenital aortic valve stenosis	65:115	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	14	96	theme	valve	2070:2074	arg1	structure					2076:2084	the human aortic valve structure	2053:2084	the human aortic valve structure	2053:2084	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	3	97	attach	linked	570:575	arg2	glycoproteins					545:557	almost all glycoproteins	534:557	almost all glycoproteins clinically linked to stenotic valvular modeling	534:605	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	3	97	attach	linked	570:575	arg1	modeling					598:605	stenotic valvular modeling	580:605	stenotic valvular modeling	580:605	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	2	98	gly	glycoprotein	371:382	arg1	glycoprotein					371:382	glycoprotein	371:382	glycoprotein	371:382	Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level.
33516683	14	99	theme	new	2148:2150	arg1	directions					2161:2170	new research directions	2148:2170	new research directions for the treatment of human aortic valve disease	2148:2218	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	6	100	theme	mass	1129:1132	arg1	spectrometry					1134:1145	High mass accuracy imaging mass spectrometry	1102:1145	High mass accuracy imaging mass spectrometry (IMS)	1102:1151	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	6	100	theme	mass	1129:1132	arg1	IMS					1148:1150	IMS	1148:1150	IMS	1148:1150	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	14	101	theme	human	2193:2197	arg1	disease					2212:2218	human aortic valve disease	2193:2218	human aortic valve disease	2193:2218	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	5	102	theme	valve	997:1001	arg1	function					1003:1010	pre-operative valve function	983:1010	pre-operative valve function spanning normal development	983:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	3	103	from	structure	746:754	arg1	disease					759:765	disease	759:765	disease	759:765	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	8	104	theme	aortic	1346:1351	arg1	valve					1353:1357	the normal aortic valve	1335:1357	the normal aortic valve	1335:1357	The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis.
33516683	11	105	from	elevation	1676:1684	arg1	independent					1692:1702	independent	1692:1702	independent	1692:1702	Three sialylated N-glycans showed common elevation in AS independent of age.
33516683	13	106	theme	Specialized	1852:1862	arg1	strategies					1874:1883	Specialized enzymatic strategies	1852:1883	Specialized enzymatic strategies	1852:1883	Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS.
33516683	5	107	theme	clinical	959:966	arg1	data					968:971	de-identified clinical data	945:971	de-identified clinical data reporting pre-operative valve function spanning normal development	945:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	14	108	theme	human	2057:2061	arg1	valve					2070:2074	human aortic valve	2057:2074	the human aortic valve structure	2053:2084	This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
33516683	11	109	theme	age	1707:1709	arg1	independent					1692:1702	independent	1692:1702	independent	1692:1702	Three sialylated N-glycans showed common elevation in AS independent of age.
33516683	0	110	theme	aortic	33:38	arg1	valve					40:44	the human aortic valve	23:44	the human aortic valve	23:44	Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
33516683	1	111	theme	aortic	277:282	arg1	leaflets					295:302	aortic valve (AV) leaflets	277:302	aortic valve (AV) leaflets	277:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
33516683	5	112	theme	aortic	1041:1046	arg1	AVI					1069:1071	AVI	1069:1071	AVI	1069:1071	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	5	112	theme	aortic	1041:1046	arg1	insufficiency					1054:1066	aortic valve insufficiency	1041:1066	aortic valve insufficiency (AVI)	1041:1072	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	5	113	theme	insufficiency	1054:1066	arg1	0-17 years					922:931	0-17 years	922:931	valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS	905:1099	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	3	114	theme	few	666:668	arg1	reports					670:676	very few reports	661:676	very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease	661:765	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	5	115	with	age	936:938	arg1	data					968:971	de-identified clinical data	945:971	de-identified clinical data reporting pre-operative valve function spanning normal development	945:1038	The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS.
33516683	8	116	located	localized	1322:1330	arg2	N-glycome					1286:1294	The N-glycome	1282:1294	The N-glycome	1282:1294	The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis.
33516683	8	116	located	localized	1322:1330	arg1	valve					1353:1357	the normal aortic valve	1335:1357	the normal aortic valve	1335:1357	The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis.
33516683	7	117	theme	related	1265:1271	arg1	enzymes					1273:1279	N-glycan related enzymes	1256:1279	N-glycan related enzymes	1256:1279	RNA-Seq was used to identify regulation of N-glycan related enzymes.
33516683	3	118	contain	contain	607:613	arg2	sites					624:628	multiple sites	615:628	multiple sites for N-glycosylation	615:648	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	3	118	contain	contain	607:613	arg1	glycoproteins					545:557	almost all glycoproteins	534:557	almost all glycoproteins clinically linked to stenotic valvular modeling	534:605	While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease.
33516683	6	119	theme	accuracy	1112:1119	arg1	spectrometry					1134:1145	High mass accuracy imaging mass spectrometry	1102:1145	High mass accuracy imaging mass spectrometry (IMS)	1102:1151	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	6	119	theme	accuracy	1112:1119	arg1	IMS					1148:1150	IMS	1148:1150	IMS	1148:1150	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	6	120	theme	imaging	1121:1127	arg1	spectrometry					1134:1145	High mass accuracy imaging mass spectrometry	1102:1145	High mass accuracy imaging mass spectrometry (IMS)	1102:1151	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	6	120	theme	imaging	1121:1127	arg1	IMS					1148:1150	IMS	1148:1150	IMS	1148:1150	High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure.
33516683	10	121	theme	sialic	1548:1553	arg1	acid					1555:1558	sialic acid	1548:1558	sialic acid (N-acetylneuraminic acid) N-glycans	1548:1594	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	10	121	theme	sialic	1548:1553	arg1	acid					1580:1583	N-acetylneuraminic acid	1561:1583	N-acetylneuraminic acid	1561:1583	In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group.
33516683	4	122	theme	spatial	788:794	arg1	localization					796:807	spatial localization	788:807	spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis	788:880	Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis.
33516683	1	123	theme	deregulated	224:234	arg1	production					263:272	deregulated extracellular matrix (ECM) production	224:272	deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets	224:302	Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies.
31829588	0	0	from	Variations	17:26	arg1	Structures					57:66	Bovine Lactoferrin Glycan Structures	31:66	Bovine Lactoferrin Glycan Structures	31:66	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures.
31829588	7	1	theme	sialic	852:857	arg1	acid					859:862	(α2,3)-linked sialic acid	838:862	(α2,3)-linked sialic acid	838:862	In some cows, we observed (α2,3)-linked sialic acid in the earliest colostrum samples.
31829588	10	2	from	glycosylation	1126:1138	arg1	period					1154:1159	the predry period	1143:1159	the predry period	1143:1159	Lactoferrin glycosylation in the predry period resembles colostrum lactoferrin.
31829588	11	3	theme	other	1280:1284	arg1	parameters					1291:1300	other milk parameters	1280:1300	other milk parameters	1280:1300	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	2	4	theme	detailed	163:170	arg1	overview					183:190	A detailed structural overview	161:190	A detailed structural overview	161:190	A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking.
31829588	10	5	theme	colostrum	1171:1179	arg1	lactoferrin					1181:1191	colostrum lactoferrin	1171:1191	colostrum lactoferrin	1171:1191	Lactoferrin glycosylation in the predry period resembles colostrum lactoferrin.
31829588	11	6	theme	glycosylation	1427:1439	arg1	functions					1374:1382	functions	1374:1382	functions	1374:1382	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	11	6	theme	glycosylation	1427:1439	arg1	regulation					1401:1410	biosynthesis regulation	1388:1410	biosynthesis regulation	1388:1410	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	5	7	theme	first	637:641	arg1	h					646:646	the first 72 h	633:646	the first 72 h	633:646	During the first 72 h, dynamic changes in lactoferrin glycosylation occurred.
31829588	3	8	theme	genetic	527:533	arg1	backgrounds					535:545	diverse genetic backgrounds	519:545	diverse genetic backgrounds	519:545	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	11	9	from	variations	1198:1207	arg1	parameters					1291:1300	other milk parameters	1280:1300	other milk parameters	1280:1300	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	11	9	from	variations	1198:1207	arg1	profiles					1238:1245	lactoferrin glycosylation profiles	1212:1245	lactoferrin glycosylation profiles	1212:1245	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	11	9	from	variations	1198:1207	arg1	concentrations					1260:1273	lactoferrin concentrations	1248:1273	lactoferrin concentrations	1248:1273	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	11	10	theme	biosynthesis	1388:1399	arg1	regulation					1401:1410	biosynthesis regulation	1388:1410	biosynthesis regulation	1388:1410	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	6	11	theme	glycans	789:795	arg1	number					752:757	the number	748:757	the number of sialylated and fucosylated glycans	748:795	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	6	11	theme	glycans	789:795	arg1	Shifts					704:709	Shifts	704:709	Shifts in the oligomannose distribution	704:742	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	6	12	from	Shifts	704:709	arg1	distribution					731:742	the oligomannose distribution	714:742	the oligomannose distribution	714:742	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	1	13	gly	glycosylation	106:118	arg1	lactoferrin					130:140	bovine lactoferrin	123:140	bovine lactoferrin	123:140	It has been reported previously that glycosylation of bovine lactoferrin changes over time.
31829588	9	14	attach	isolated	1054:1061	arg1	milk					1082:1085	pooled mature milk	1068:1085	pooled mature milk	1068:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	9	14	attach	isolated	1054:1061	arg2	lactoferrins					1041:1052	commercial lactoferrins	1030:1052	commercial lactoferrins isolated from pooled mature milk	1030:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	6	15	theme	fucosylated	777:787	arg1	glycans					789:795	fucosylated glycans	777:795	fucosylated glycans	777:795	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	9	16	from	addition	990:997	arg1	stable					1092:1097	stable	1092:1097	stable	1092:1097	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	9	16	from	addition	990:997	arg1	profiles					1018:1025	the glycosylation profiles	1000:1025	the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk	1000:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	11	17	theme	lactoferrin	1415:1425	arg1	glycosylation					1427:1439	lactoferrin glycosylation	1415:1439	lactoferrin glycosylation	1415:1439	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	11	18	theme	lactoferrin	1248:1258	arg1	concentrations					1260:1273	lactoferrin concentrations	1248:1273	lactoferrin concentrations	1248:1273	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	3	19	theme	lactoferrin	371:381	arg1	glycoprofile					355:366	glycoprofile	355:366	glycoprofile	355:366	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	9	20	theme	commercial	1030:1039	arg1	lactoferrins					1041:1052	commercial lactoferrins	1030:1052	commercial lactoferrins isolated from pooled mature milk	1030:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	3	21	theme	predry	420:425	arg1	milk					441:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	0	22	theme	Temporal	8:15	arg1	Variations					17:26	Dynamic Temporal Variations	0:26	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures	0:66	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures.
31829588	9	23	gly	glycosylation	1004:1016	arg1	lactoferrins					1041:1052	commercial lactoferrins	1030:1052	commercial lactoferrins isolated from pooled mature milk	1030:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	6	24	theme	sialylated	762:771	arg1	number					752:757	the number	748:757	the number of sialylated and fucosylated glycans	748:795	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	6	24	theme	sialylated	762:771	arg1	Shifts					704:709	Shifts	704:709	Shifts in the oligomannose distribution	704:742	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	9	25	theme	lactoferrins	1041:1052	arg1	stable					1092:1097	stable	1092:1097	stable	1092:1097	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	9	25	theme	lactoferrins	1041:1052	arg1	profiles					1018:1025	the glycosylation profiles	1000:1025	the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk	1000:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	3	26	theme	mature	408:413	arg1	milk					441:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	0	27	theme	Dynamic	0:6	arg1	Variations					17:26	Dynamic Temporal Variations	0:26	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures	0:66	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures.
31829588	11	28	theme	milk	1286:1289	arg1	parameters					1291:1300	other milk parameters	1280:1300	other milk parameters	1280:1300	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	7	29	link	-linked	844:850	arg1	acid					859:862	(α2,3)-linked sialic acid	838:862	(α2,3)-linked sialic acid	838:862	In some cows, we observed (α2,3)-linked sialic acid in the earliest colostrum samples.
31829588	11	30	theme	detailed	1310:1317	arg1	information					1319:1329	detailed information	1310:1329	detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation	1310:1439	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	7	31	theme	colostrum	880:888	arg1	samples					890:896	the earliest colostrum samples	867:896	the earliest colostrum samples	867:896	In some cows, we observed (α2,3)-linked sialic acid in the earliest colostrum samples.
31829588	11	32	dep	functions	1374:1382	arg1	the					1370:1372	the	1370:1372	the	1370:1372	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	3	33	theme	diverse	519:525	arg1	backgrounds					535:545	diverse genetic backgrounds	519:545	diverse genetic backgrounds	519:545	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	4	34	theme	lactoferrin	605:615	arg1	samples					617:623	commercial bovine lactoferrin samples	587:623	commercial bovine lactoferrin samples	587:623	In addition, comparisons are made with commercial bovine lactoferrin samples.
31829588	3	35	theme	glycoprofile	355:366	arg1	milk					441:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	5	36	theme	lactoferrin	668:678	arg1	glycosylation					680:692	lactoferrin glycosylation	668:692	lactoferrin glycosylation	668:692	During the first 72 h, dynamic changes in lactoferrin glycosylation occurred.
31829588	3	37	theme	subsequent	475:484	arg1	cycles					496:501	two subsequent lactation cycles	471:501	two subsequent lactation cycles	471:501	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	9	38	theme	pooled	1068:1073	arg1	milk					1082:1085	pooled mature milk	1068:1085	pooled mature milk	1068:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	4	39	theme	bovine	598:603	arg1	samples					617:623	commercial bovine lactoferrin samples	587:623	commercial bovine lactoferrin samples	587:623	In addition, comparisons are made with commercial bovine lactoferrin samples.
31829588	0	40	theme	Lactoferrin	38:48	arg1	Structures					57:66	Bovine Lactoferrin Glycan Structures	31:66	Bovine Lactoferrin Glycan Structures	31:66	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures.
31829588	2	41	theme	lactation	234:242	arg1	course					224:229	the whole course	214:229	the whole course of lactation	214:242	A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking.
31829588	9	42	theme	mature	1075:1080	arg1	milk					1082:1085	pooled mature milk	1068:1085	pooled mature milk	1068:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	3	43	theme	period	427:432	arg1	milk					441:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	0	44	theme	Bovine	31:36	arg1	Structures					57:66	Bovine Lactoferrin Glycan Structures	31:66	Bovine Lactoferrin Glycan Structures	31:66	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures.
31829588	10	45	theme	Lactoferrin	1114:1124	arg1	glycosylation					1126:1138	Lactoferrin glycosylation	1114:1138	Lactoferrin glycosylation in the predry period	1114:1159	Lactoferrin glycosylation in the predry period resembles colostrum lactoferrin.
31829588	2	46	theme	structural	172:181	arg1	overview					183:190	A detailed structural overview	161:190	A detailed structural overview	161:190	A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking.
31829588	3	47	theme	mature	434:439	arg1	milk					441:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk	351:444	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	3	48	attach	isolated	383:390	arg1	colostrum					397:405	colostrum	397:405	colostrum	397:405	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	3	48	attach	isolated	383:390	arg2	lactoferrin					371:381	lactoferrin	371:381	lactoferrin isolated from colostrum	371:405	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	11	49	theme	lactoferrin	1212:1222	arg1	profiles					1238:1245	lactoferrin glycosylation profiles	1212:1245	lactoferrin glycosylation profiles	1212:1245	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	0	50	theme	Glycan	50:55	arg1	Structures					57:66	Bovine Lactoferrin Glycan Structures	31:66	Bovine Lactoferrin Glycan Structures	31:66	Dynamic Temporal Variations in Bovine Lactoferrin Glycan Structures.
31829588	6	51	gly	fucosylated	777:787	arg1	glycans					789:795	fucosylated glycans	777:795	fucosylated glycans	777:795	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	2	52	theme	whole	218:222	arg1	course					224:229	the whole course	214:229	the whole course of lactation	214:242	A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking.
31829588	1	53	theme	bovine	123:128	arg1	lactoferrin					130:140	bovine lactoferrin	123:140	bovine lactoferrin	123:140	It has been reported previously that glycosylation of bovine lactoferrin changes over time.
31829588	6	54	from	number	752:757	arg1	distribution					731:742	the oligomannose distribution	714:742	the oligomannose distribution	714:742	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	5	55	theme	dynamic	649:655	arg1	changes					657:663	dynamic changes	649:663	dynamic changes in lactoferrin glycosylation	649:692	During the first 72 h, dynamic changes in lactoferrin glycosylation occurred.
31829588	2	56	theme	period	262:267	arg1	milk					269:272	predry period milk	255:272	predry period milk	255:272	A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking.
31829588	6	57	theme	oligomannose	718:729	arg1	distribution					731:742	the oligomannose distribution	714:742	the oligomannose distribution	714:742	Shifts in the oligomannose distribution and the number of sialylated and fucosylated glycans were observed.
31829588	1	58	theme	lactoferrin	130:140	arg1	glycosylation					106:118	glycosylation	106:118	glycosylation of bovine lactoferrin	106:140	It has been reported previously that glycosylation of bovine lactoferrin changes over time.
31829588	7	59	theme	earliest	871:878	arg1	samples					890:896	the earliest colostrum samples	867:896	the earliest colostrum samples	867:896	In some cows, we observed (α2,3)-linked sialic acid in the earliest colostrum samples.
31829588	10	60	theme	predry	1147:1152	arg1	period					1154:1159	the predry period	1143:1159	the predry period	1143:1159	Lactoferrin glycosylation in the predry period resembles colostrum lactoferrin.
31829588	11	61	theme	glycosylation	1224:1236	arg1	profiles					1238:1245	lactoferrin glycosylation profiles	1212:1245	lactoferrin glycosylation profiles	1212:1245	The variations in lactoferrin glycosylation profiles, lactoferrin concentrations, and other milk parameters provide detailed information that potentially assists in unraveling the functions and biosynthesis regulation of lactoferrin glycosylation.
31829588	2	62	theme	changes	201:207	arg1	overview					183:190	A detailed structural overview	161:190	A detailed structural overview	161:190	A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking.
31829588	2	63	theme	predry	255:260	arg1	milk					269:272	predry period milk	255:272	predry period milk	255:272	A detailed structural overview of these changes over the whole course of lactation, including predry period milk, is lacking.
31829588	3	64	from	backgrounds	535:545	arg1	cows					509:512	8 cows	507:512	8 cows from diverse genetic backgrounds	507:545	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	5	65	from	changes	657:663	arg1	glycosylation					680:692	lactoferrin glycosylation	668:692	lactoferrin glycosylation	668:692	During the first 72 h, dynamic changes in lactoferrin glycosylation occurred.
31829588	3	66	theme	high-throughput	304:318	arg1	method					329:334	a high-throughput analysis method	302:334	a high-throughput analysis method	302:334	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	9	67	theme	glycosylation	1004:1016	arg1	stable					1092:1097	stable	1092:1097	stable	1092:1097	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	9	67	theme	glycosylation	1004:1016	arg1	profiles					1018:1025	the glycosylation profiles	1000:1025	the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk	1000:1085	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	10	68	gly	glycosylation	1126:1138	arg1	period					1154:1159	the predry period	1143:1159	the predry period	1143:1159	Lactoferrin glycosylation in the predry period resembles colostrum lactoferrin.
31829588	9	69	from	stable	1092:1097	arg1	addition					990:997	addition	990:997	addition	990:997	In addition, the glycosylation profiles of commercial lactoferrins isolated from pooled mature milk were stable over the year.
31829588	3	70	theme	lactation	486:494	arg1	cycles					496:501	two subsequent lactation cycles	471:501	two subsequent lactation cycles	471:501	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	4	71	theme	commercial	587:596	arg1	samples					617:623	commercial bovine lactoferrin samples	587:623	commercial bovine lactoferrin samples	587:623	In addition, comparisons are made with commercial bovine lactoferrin samples.
31829588	3	72	theme	analysis	320:327	arg1	method					329:334	a high-throughput analysis method	302:334	a high-throughput analysis method	302:334	In this study, a high-throughput analysis method was applied to the glycoprofile of lactoferrin isolated from colostrum, mature, and predry period mature milk, which was analyzed over two subsequent lactation cycles for 8 cows from diverse genetic backgrounds.
31829588	7	73	theme	-linked	844:850	arg1	acid					859:862	(α2,3)-linked sialic acid	838:862	(α2,3)-linked sialic acid	838:862	In some cows, we observed (α2,3)-linked sialic acid in the earliest colostrum samples.
32475665	7	0	link	3-linked	1289:1296	arg1	mannopyranosyl					1298:1311	3-linked mannopyranosyl	1289:1311	3-linked mannopyranosyl	1289:1311	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	4	1	theme	Glycosyl	517:524	arg1	analysis					538:545	Glycosyl composition analysis	517:545	Glycosyl composition analysis	517:545	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	7	2	theme	2,6-linked	1332:1341	arg1	mannopyranosyl					1343:1356	2,6-linked mannopyranosyl	1332:1356	2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%)	1332:1382	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	2	theme	2,6-linked	1332:1341	arg1	2,6-Man					1359:1365	2,6-Man	1359:1365	2,6-Man	1359:1365	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	4	3	theme	resonance	625:633	arg1	spectroscopy					635:646	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	4	4	dep	along	565:569	arg1	with					571:574	with	571:574	with	571:574	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	4	5	theme	magnetic	616:623	arg1	resonance					625:633	nuclear magnetic resonance	608:633	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	8	6	theme	magnetic	1429:1436	arg1	resonance					1438:1446	2-dimensional nuclear magnetic resonance	1407:1446	2-dimensional nuclear magnetic resonance spectroscopy	1407:1459	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	9	7	theme	possible	1730:1737	arg1	structure					1739:1747	A possible structure	1728:1747	A possible structure of EPS in F2 and F3	1728:1767	A possible structure of EPS in F2 and F3 was proposed.
32475665	5	8	with	F1	771:772	arg1	weights					832:838	average molecular weights	814:838	average molecular weights of approximately 511, 40, and 5 kDa	814:874	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	8	9	theme	α-d-glucopyranosyl	1558:1575	arg1	chains					1548:1553	linear chains	1541:1553	linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages	1541:1682	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	6	10	theme	glucose	953:959	arg1	dominance					940:948	the dominance	936:948	the dominance of glucose, galactose, and mannose in all 3 fractions	936:1002	Monosaccharide composition analysis revealed the dominance of glucose, galactose, and mannose in all 3 fractions.
32475665	3	11	theme	exopolysaccharide	393:409	arg1	fractionation					376:388	fractionation	376:388	fractionation of exopolysaccharide	376:409	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	3	11	theme	exopolysaccharide	393:409	arg1	purification					359:370	Further purification	351:370	Further purification	351:370	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	0	12	from	ASCC	81:84	arg1	characterization					11:26	Structural characterization	0:26	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.	0:90	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.
32475665	2	13	theme	ASCC	302:305	arg1	1275					307:310	S. thermophilus ASCC 1275	286:310	S. thermophilus ASCC 1275	286:310	Crude EPS was extracted from S. thermophilus ASCC 1275 and partially purified using dialysis.
32475665	7	14	theme	present	1203:1209	arg1	t-Gal					1067:1071	t-Gal	1067:1071	t-Gal	1067:1071	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	14	theme	present	1203:1209	arg1	galactopyranosyl					1049:1064	terminal galactopyranosyl	1040:1064	terminal galactopyranosyl (t-Gal)	1040:1072	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	15	theme	terminal	1040:1047	arg1	t-Gal					1067:1071	t-Gal	1067:1071	t-Gal	1067:1071	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	15	theme	terminal	1040:1047	arg1	galactopyranosyl					1049:1064	terminal galactopyranosyl	1040:1064	terminal galactopyranosyl (t-Gal)	1040:1072	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	2	16	theme	thermophilus	289:300	arg1	1275					307:310	S. thermophilus ASCC 1275	286:310	S. thermophilus ASCC 1275	286:310	Crude EPS was extracted from S. thermophilus ASCC 1275 and partially purified using dialysis.
32475665	7	17	link	2,6-linked	1332:1341	arg1	mannopyranosyl					1343:1356	2,6-linked mannopyranosyl	1332:1356	2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%)	1332:1382	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	17	link	2,6-linked	1332:1341	arg1	2,6-Man					1359:1365	2,6-Man	1359:1365	2,6-Man	1359:1365	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	5	18	theme	molecular	822:830	arg1	weights					832:838	average molecular weights	814:838	average molecular weights of approximately 511, 40, and 5 kDa	814:874	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	7	19	attach	present	1203:1209	arg2	t-Gal					1067:1071	t-Gal	1067:1071	t-Gal	1067:1071	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	19	attach	present	1203:1209	arg2	galactopyranosyl					1049:1064	terminal galactopyranosyl	1040:1064	terminal galactopyranosyl (t-Gal)	1040:1072	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	19	attach	present	1203:1209	arg1	F2					1214:1215	F2	1214:1215	F2	1214:1215	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	3	20	theme	Superose	441:448	arg1	column					452:457	a Superose 6 column	439:457	a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA)	439:514	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	2	21	theme	S.	286:287	arg1	1275					307:310	S. thermophilus ASCC 1275	286:310	S. thermophilus ASCC 1275	286:310	Crude EPS was extracted from S. thermophilus ASCC 1275 and partially purified using dialysis.
32475665	8	22	theme	β-d-glucopyranosyl	1589:1606	arg1	chains					1548:1553	linear chains	1541:1553	linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages	1541:1682	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	1	23	theme	high-EPS-producing	175:192	arg1	1275					251:254	Streptococcus thermophilus ASCC 1275	219:254	Streptococcus thermophilus ASCC 1275	219:254	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	1	23	theme	high-EPS-producing	175:192	arg1	bacterium					208:216	a high-EPS-producing dairy starter bacterium	173:216	a high-EPS-producing dairy starter bacterium	173:216	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	7	24	theme	3-linked	1108:1115	arg1	3-Galf					1135:1140	3-Galf	1135:1140	3-Galf	1135:1140	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	24	theme	3-linked	1108:1115	arg1	galactofuranosyl					1117:1132	3-linked galactofuranosyl	1108:1132	3-linked galactofuranosyl (3-Galf)	1108:1141	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	25	theme	3,6-linked	1148:1157	arg1	3,6-Glc					1175:1181	3,6-Glc	1175:1181	3,6-Glc	1175:1181	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	25	theme	3,6-linked	1148:1157	arg1	glucopyranosyl					1159:1172	3,6-linked glucopyranosyl	1148:1172	3,6-linked glucopyranosyl (3,6-Glc)	1148:1182	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	26	from	present	1203:1209	arg1	F2					1214:1215	F2	1214:1215	F2	1214:1215	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	27	theme	3-linked	1289:1296	arg1	mannopyranosyl					1298:1311	3-linked mannopyranosyl	1289:1311	3-linked mannopyranosyl	1289:1311	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	1	28	theme	dairy	194:198	arg1	1275					251:254	Streptococcus thermophilus ASCC 1275	219:254	Streptococcus thermophilus ASCC 1275	219:254	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	1	28	theme	dairy	194:198	arg1	bacterium					208:216	a high-EPS-producing dairy starter bacterium	173:216	a high-EPS-producing dairy starter bacterium	173:216	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	0	29	theme	Structural	0:9	arg1	characterization					11:26	Structural characterization	0:26	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.	0:90	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.
32475665	7	30	dep	2,6-Man	1359:1365	arg1	%					1381:1381	total ∼28 mol%	1368:1381	total ∼28 mol%	1368:1381	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	31	theme	∼28	1374:1376	arg1	%					1381:1381	total ∼28 mol%	1368:1381	total ∼28 mol%	1368:1381	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	32	link	3,6-linked	1148:1157	arg1	3,6-Glc					1175:1181	3,6-Glc	1175:1181	3,6-Glc	1175:1181	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	32	link	3,6-linked	1148:1157	arg1	glucopyranosyl					1159:1172	3,6-linked glucopyranosyl	1148:1172	3,6-linked glucopyranosyl (3,6-Glc)	1148:1182	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	6	33	theme	galactose	962:970	arg1	dominance					940:948	the dominance	936:948	the dominance of glucose, galactose, and mannose in all 3 fractions	936:1002	Monosaccharide composition analysis revealed the dominance of glucose, galactose, and mannose in all 3 fractions.
32475665	1	34	theme	starter	200:206	arg1	1275					251:254	Streptococcus thermophilus ASCC 1275	219:254	Streptococcus thermophilus ASCC 1275	219:254	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	1	34	theme	starter	200:206	arg1	bacterium					208:216	a high-EPS-producing dairy starter bacterium	173:216	a high-EPS-producing dairy starter bacterium	173:216	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	0	35	theme	exopolysaccharide	31:47	arg1	characterization					11:26	Structural characterization	0:26	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.	0:90	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.
32475665	4	36	theme	1-dimensional	576:588	arg1	spectroscopy					635:646	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	5	37	theme	permeation	733:742	arg1	chromatography					744:757	gel permeation chromatography	729:757	gel permeation chromatography	729:757	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	7	38	from	F2	1214:1215	arg1	present					1203:1209	present	1203:1209	present	1203:1209	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	39	link	3-linked	1075:1082	arg1	3-Glc					1100:1104	3-Glc	1100:1104	3-Glc	1100:1104	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	39	link	3-linked	1075:1082	arg1	glucopyranosyl					1084:1097	3-linked glucopyranosyl	1075:1097	3-linked glucopyranosyl (3-Glc)	1075:1105	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	3	40	dep	column	452:457	arg1	Cytiva/Global					460:472	Cytiva/Global	460:472	Cytiva/Global	460:472	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	3	40	dep	column	452:457	arg1	MA					512:513	MA	512:513	MA	512:513	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	4	41	theme	nuclear	608:614	arg1	resonance					625:633	nuclear magnetic resonance	608:633	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	9	42	from	structure	1739:1747	arg1	F3					1766:1767	F3	1766:1767	F3	1766:1767	A possible structure of EPS in F2 and F3 was proposed.
32475665	9	42	from	structure	1739:1747	arg1	F2					1759:1760	F2	1759:1760	F2	1759:1760	A possible structure of EPS in F2 and F3 was proposed.
32475665	5	43	with	F3	798:799	arg1	weights					832:838	average molecular weights	814:838	average molecular weights of approximately 511, 40, and 5 kDa	814:874	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	0	44	theme	Streptococcus	54:66	arg1	ASCC					81:84	Streptococcus thermophilus ASCC 1275	54:89	Streptococcus thermophilus ASCC 1275	54:89	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.
32475665	4	45	theme	2-dimensional	594:606	arg1	spectroscopy					635:646	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy	576:646	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	6	46	from	dominance	940:948	arg1	fractions					994:1002	all 3 fractions	988:1002	all 3 fractions	988:1002	Monosaccharide composition analysis revealed the dominance of glucose, galactose, and mannose in all 3 fractions.
32475665	3	47	theme	Sciences	479:486	arg1	Solutions					488:496	Life Sciences Solutions	474:496	Cytiva/Global Life Sciences Solutions	460:496	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	2	48	theme	Crude	257:261	arg1	EPS					263:265	Crude EPS	257:265	Crude EPS	257:265	Crude EPS was extracted from S. thermophilus ASCC 1275 and partially purified using dialysis.
32475665	1	49	theme	Streptococcus	219:231	arg1	1275					251:254	Streptococcus thermophilus ASCC 1275	219:254	Streptococcus thermophilus ASCC 1275	219:254	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	1	49	theme	Streptococcus	219:231	arg1	bacterium					208:216	a high-EPS-producing dairy starter bacterium	173:216	a high-EPS-producing dairy starter bacterium	173:216	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	6	50	theme	composition	906:916	arg1	analysis					918:925	Monosaccharide composition analysis	891:925	Monosaccharide composition analysis	891:925	Monosaccharide composition analysis revealed the dominance of glucose, galactose, and mannose in all 3 fractions.
32475665	5	51	theme	termed	764:769	arg1	F1					771:772	termed F1	764:772	termed F1 (2.6%)	764:779	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	5	51	theme	termed	764:769	arg1	%					778:778	2.6%	775:778	2.6%	775:778	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	8	52	theme	β-d-galactofuranosyl	1624:1643	arg1	chains					1548:1553	linear chains	1541:1553	linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages	1541:1682	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	4	53	theme	EPS	690:692	arg1	structure					677:685	the structure	673:685	the structure of EPS	673:692	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	7	54	theme	3-linked	1075:1082	arg1	3-Glc					1100:1104	3-Glc	1100:1104	3-Glc	1100:1104	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	54	theme	3-linked	1075:1082	arg1	glucopyranosyl					1084:1097	3-linked glucopyranosyl	1075:1097	3-linked glucopyranosyl (3-Glc)	1075:1105	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	4	55	theme	linkage	548:554	arg1	analysis					556:563	linkage analysis	548:563	linkage analysis	548:563	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	8	56	theme	nuclear	1421:1427	arg1	resonance					1438:1446	2-dimensional nuclear magnetic resonance	1407:1446	2-dimensional nuclear magnetic resonance spectroscopy	1407:1459	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	3	57	dep	Cytiva/Global	460:472	arg1	Solutions					488:496	Life Sciences Solutions	474:496	Cytiva/Global Life Sciences Solutions	460:496	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	8	58	theme	2-dimensional	1407:1419	arg1	resonance					1438:1446	2-dimensional nuclear magnetic resonance	1407:1446	2-dimensional nuclear magnetic resonance spectroscopy	1407:1459	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	0	59	theme	thermophilus	68:79	arg1	ASCC					81:84	Streptococcus thermophilus ASCC 1275	54:89	Streptococcus thermophilus ASCC 1275	54:89	Structural characterization of exopolysaccharide from Streptococcus thermophilus ASCC 1275.
32475665	7	60	theme	total	1368:1372	arg1	%					1381:1381	total ∼28 mol%	1368:1381	total ∼28 mol%	1368:1381	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	8	61	theme	resonance	1438:1446	arg1	spectroscopy					1448:1459	2-dimensional nuclear magnetic resonance spectroscopy	1407:1459	2-dimensional nuclear magnetic resonance spectroscopy	1407:1459	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	9	62	theme	EPS	1752:1754	arg1	structure					1739:1747	A possible structure	1728:1747	A possible structure of EPS in F2 and F3	1728:1767	A possible structure of EPS in F2 and F3 was proposed.
32475665	8	63	theme	1→2	1507:1509	arg1	linkages					1512:1519	(1→2) linkages	1506:1519	(1→2) linkages	1506:1519	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	5	64	with	F2	782:783	arg1	weights					832:838	average molecular weights	814:838	average molecular weights of approximately 511, 40, and 5 kDa	814:874	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	1	65	dep	Streptococcus	219:231	arg1	thermophilus					233:244	thermophilus	233:244	thermophilus	233:244	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	8	66	theme	1→3	1670:1672	arg1	linkages					1675:1682	(1→3) linkages	1669:1682	(1→3) linkages	1669:1682	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	5	67	theme	kDa	872:874	arg1	weights					832:838	average molecular weights	814:838	average molecular weights of approximately 511, 40, and 5 kDa	814:874	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	1	68	theme	ASCC	246:249	arg1	1275					251:254	Streptococcus thermophilus ASCC 1275	219:254	Streptococcus thermophilus ASCC 1275	219:254	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	1	68	theme	ASCC	246:249	arg1	bacterium					208:216	a high-EPS-producing dairy starter bacterium	173:216	a high-EPS-producing dairy starter bacterium	173:216	In this study, we purified and characterized exopolysaccharide (EPS) produced by a high-EPS-producing dairy starter bacterium, Streptococcus thermophilus ASCC 1275.
32475665	5	69	theme	gel	729:731	arg1	chromatography					744:757	gel permeation chromatography	729:757	gel permeation chromatography	729:757	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	7	70	theme	mol	1378:1380	arg1	%					1381:1381	total ∼28 mol%	1368:1381	total ∼28 mol%	1368:1381	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	71	theme	terminal	1251:1258	arg1	t-Man					1276:1280	t-Man	1276:1280	t-Man	1276:1280	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	71	theme	terminal	1251:1258	arg1	mannopyranosyl					1260:1273	terminal mannopyranosyl	1251:1273	terminal mannopyranosyl (t-Man)	1251:1281	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	71	theme	terminal	1251:1258	arg1	2-Man+3-Man					1314:1324	2-Man+3-Man	1314:1324	2-Man+3-Man	1314:1324	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	72	located	observed	1020:1027	arg1	F3					1032:1033	F3	1032:1033	F3	1032:1033	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	72	located	observed	1020:1027	arg2	linkages					1011:1018	Major linkages	1005:1018	Major linkages observed in F3	1005:1033	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	73	theme	mol	1232:1234	arg1	%					1235:1235	48 mol%	1229:1235	48 mol%	1229:1235	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	73	theme	mol	1232:1234	arg1	4-Glc					1222:1226	4-Glc	1222:1226	4-Glc (48 mol%)	1222:1236	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	6	74	theme	mannose	977:983	arg1	dominance					940:948	the dominance	936:948	the dominance of glucose, galactose, and mannose in all 3 fractions	936:1002	Monosaccharide composition analysis revealed the dominance of glucose, galactose, and mannose in all 3 fractions.
32475665	3	75	theme	Further	351:357	arg1	purification					359:370	Further purification	351:370	Further purification	351:370	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	5	76	theme	average	814:820	arg1	weights					832:838	average molecular weights	814:838	average molecular weights of approximately 511, 40, and 5 kDa	814:874	Three fractions (F) obtained from gel permeation chromatography were termed F1 (2.6%), F2 (45.8%), and F3 (51.6%) with average molecular weights of approximately 511, 40, and 5 kDa, respectively.
32475665	7	77	link	3-linked	1108:1115	arg1	3-Galf					1135:1140	3-Galf	1135:1140	3-Galf	1135:1140	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	77	link	3-linked	1108:1115	arg1	galactofuranosyl					1117:1132	3-linked galactofuranosyl	1108:1132	3-linked galactofuranosyl (3-Galf)	1108:1141	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	8	78	theme	linear	1541:1546	arg1	chains					1548:1553	linear chains	1541:1553	linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages	1541:1682	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	3	79	theme	Life	474:477	arg1	Solutions					488:496	Life Sciences Solutions	474:496	Cytiva/Global Life Sciences Solutions	460:496	Further purification and fractionation of exopolysaccharide was conducted using HPLC on a Superose 6 column (Cytiva/Global Life Sciences Solutions, Marlborough, MA).
32475665	8	80	from	linkage	1713:1719	arg1	F3					1724:1725	F3	1724:1725	F3	1724:1725	The 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy revealed that F2 comprised mannans linked by (1→2) linkages and F3 consisted of linear chains of α-d-glucopyranosyl (α-d-Glcp), β-d-glucopyranosyl (β-d-Glcp), and β-d-galactofuranosyl (β-d-Galf) connected by (1→3) linkages; branching was through (1→6) linkage in F3.
32475665	4	81	theme	composition	526:536	arg1	analysis					538:545	Glycosyl composition analysis	517:545	Glycosyl composition analysis	517:545	Glycosyl composition analysis, linkage analysis along with 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy were performed to deduce the structure of EPS.
32475665	7	82	theme	Major	1005:1009	arg1	linkages					1011:1018	Major linkages	1005:1018	Major linkages observed in F3	1005:1033	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	7	83	theme	major	1188:1192	arg1	linkages					1194:1201	major linkages	1188:1201	major linkages	1188:1201	Major linkages observed in F3 were terminal galactopyranosyl (t-Gal), 3-linked glucopyranosyl (3-Glc), 3-linked galactofuranosyl (3-Galf), and 3,6-linked glucopyranosyl (3,6-Glc) and major linkages present in F2 were 4-Glc (48 mol%), followed by terminal mannopyranosyl (t-Man), 2- + 3-linked mannopyranosyl (2-Man+3-Man), and 2,6-linked mannopyranosyl (2,6-Man; total ∼28 mol%).
32475665	6	84	theme	Monosaccharide	891:904	arg1	analysis					918:925	Monosaccharide composition analysis	891:925	Monosaccharide composition analysis	891:925	Monosaccharide composition analysis revealed the dominance of glucose, galactose, and mannose in all 3 fractions.
32001617	2	0	theme	species-specific	489:504	arg1	glycoconjugates					506:520	species-specific glycoconjugates	489:520	species-specific glycoconjugates	489:520	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	2	0	theme	species-specific	489:504	arg1	ones					533:536	ones	533:536	ones heavily modified by fucose, sulfate, and sialic acid residues	533:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	3	1	theme	in-depth	708:715	arg1	member					794:799	an example member	783:799	an example member of the class Ophiuroidea	783:824	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	1	theme	in-depth	708:715	arg1	analysis					717:724	an in-depth analysis	705:724	an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi)	705:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	6	2	theme	phosphate	1253:1261	arg1	residues					1263:1270	phosphate residues	1253:1270	phosphate residues	1253:1270	70% of these N-glycans were anionic, carrying either sialic acid, sulfate, or phosphate residues.
32001617	7	3	theme	lower	1427:1431	arg1	organisms					1433:1441	lower organisms	1427:1441	lower organisms	1427:1441	In terms of glycophylogeny, our data position the brittle star between invertebrates and vertebrates and confirm the high diversity of N-glycosylation in lower organisms.
32001617	2	4	theme	no	367:368	arg1	data					370:373	almost no data	360:373	almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues	360:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	5	5	theme	reminiscent	1074:1084	arg1	structures					1063:1072	hybrid and complex oligosaccharide structures	1028:1072	structures	1063:1072	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	3	6	theme	Ophiuroidea	814:824	arg1	member					794:799	an example member	783:799	an example member of the class Ophiuroidea	783:824	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	6	theme	Ophiuroidea	814:824	arg1	analysis					717:724	an in-depth analysis	705:724	an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi)	705:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	7	theme	example	786:792	arg1	member					794:799	an example member	783:799	an example member of the class Ophiuroidea	783:824	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	7	theme	example	786:792	arg1	analysis					717:724	an in-depth analysis	705:724	an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi)	705:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	6	8	theme	sialic	1228:1233	arg1	acid					1235:1238	sialic acid	1228:1238	sialic acid	1228:1238	70% of these N-glycans were anionic, carrying either sialic acid, sulfate, or phosphate residues.
32001617	3	9	theme	carbohydrate	643:654	arg1	structures					656:665	carbohydrate structures	643:665	carbohydrate structures	643:665	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	0	10	theme	vertebrate	91:100	arg1	features					130:137	both vertebrate and invertebrate N-glycomic features	86:137	both vertebrate and invertebrate N-glycomic features	86:137	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	7	11	theme	brittle	1323:1329	arg1	star					1331:1334	the brittle star	1319:1334	the brittle star	1319:1334	In terms of glycophylogeny, our data position the brittle star between invertebrates and vertebrates and confirm the high diversity of N-glycosylation in lower organisms.
32001617	4	12	theme	multi-step	855:864	arg1	analysis					875:882	a multi-step N-glycan analysis	853:882	a multi-step N-glycan analysis	853:882	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	5	13	theme	structures	1163:1172	arg1	wealth					1018:1023	a wealth	1016:1023	a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures	1016:1172	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	5	14	theme	structures	1063:1072	arg1	wealth					1018:1023	a wealth	1016:1023	a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures	1016:1172	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	4	15	theme	chemical	922:929	arg1	treatments					931:940	various exoglyosidase and chemical treatments	896:940	various exoglyosidase and chemical treatments	896:940	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	3	16	theme	N-glycans	729:737	arg1	member					794:799	an example member	783:799	an example member of the class Ophiuroidea	783:824	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	16	theme	N-glycans	729:737	arg1	analysis					717:724	an in-depth analysis	705:724	an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi)	705:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	7	17	theme	N-glycosylation	1408:1422	arg1	diversity					1395:1403	the high diversity	1386:1403	the high diversity of N-glycosylation in lower organisms	1386:1441	In terms of glycophylogeny, our data position the brittle star between invertebrates and vertebrates and confirm the high diversity of N-glycosylation in lower organisms.
32001617	3	18	theme	class	808:812	arg1	Ophiuroidea					814:824	the class Ophiuroidea	804:824	the class Ophiuroidea	804:824	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	0	19	theme	invertebrate	106:117	arg1	features					130:137	both vertebrate and invertebrate N-glycomic features	86:137	both vertebrate and invertebrate N-glycomic features	86:137	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	7	20	from	diversity	1395:1403	arg1	organisms					1433:1441	lower organisms	1427:1441	lower organisms	1427:1441	In terms of glycophylogeny, our data position the brittle star between invertebrates and vertebrates and confirm the high diversity of N-glycosylation in lower organisms.
32001617	7	21	theme	high	1390:1393	arg1	diversity					1395:1403	the high diversity	1386:1403	the high diversity of N-glycosylation in lower organisms	1386:1441	In terms of glycophylogeny, our data position the brittle star between invertebrates and vertebrates and confirm the high diversity of N-glycosylation in lower organisms.
32001617	7	22	from	position	1310:1317	arg1	terms					1276:1280	terms	1276:1280	terms of glycophylogeny	1276:1298	In terms of glycophylogeny, our data position the brittle star between invertebrates and vertebrates and confirm the high diversity of N-glycosylation in lower organisms.
32001617	1	23	theme	primitive	171:179	arg1	deuterostomes					181:193	the most primitive deuterostomes	162:193	the most primitive deuterostomes	162:193	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	5	24	theme	those	1089:1093	arg1	reminiscent					1074:1084	reminiscent	1074:1084	reminiscent	1074:1084	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	2	25	theme	N-glycomic	399:408	arg1	capacity					410:417	the N-glycomic capacity	395:417	the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues	395:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	3	26	from	analysis	717:724	arg1	star					754:757	a brittle star	744:757	a brittle star (Ophiactis savignyi)	744:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	26	from	analysis	717:724	arg1	Ophiactis					760:768	Ophiactis	760:768	Ophiactis	760:768	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	0	27	from	nexus	33:37	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi	0:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	3	28	from	star	754:757	arg1	member					794:799	an example member	783:799	an example member of the class Ophiuroidea	783:824	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	28	from	star	754:757	arg1	N-glycans					729:737	N-glycans	729:737	N-glycans from a brittle star (Ophiactis savignyi)	729:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	28	from	star	754:757	arg1	analysis					717:724	an in-depth analysis	705:724	an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi)	705:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	4	29	theme	MALDI-TOF	962:970	arg1	MS					972:973	MALDI-TOF MS	962:973	MALDI-TOF MS	962:973	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	4	30	theme	N-glycan	866:873	arg1	analysis					875:882	a multi-step N-glycan analysis	853:882	a multi-step N-glycan analysis	853:882	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	1	31	theme	close	281:285	arg1	relationship					300:311	their close evolutionary relationship	275:311	their close evolutionary relationship to this phylogenetic group	275:338	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	5	32	theme	hybrid	1028:1033	arg1	structures					1063:1072	hybrid and complex oligosaccharide structures	1028:1072	structures	1063:1072	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	7	33	theme	glycophylogeny	1285:1298	arg1	terms					1276:1280	terms	1276:1280	terms of glycophylogeny	1276:1298	In terms of glycophylogeny, our data position the brittle star between invertebrates and vertebrates and confirm the high diversity of N-glycosylation in lower organisms.
32001617	0	34	theme	evolutionary	20:31	arg1	nexus					33:37	an evolutionary nexus	17:37	an evolutionary nexus	17:37	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	1	35	theme	evolutionary	287:298	arg1	relationship					300:311	their close evolutionary relationship	275:311	their close evolutionary relationship to this phylogenetic group	275:338	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	2	36	theme	sulfate	566:572	arg1	residues					591:598	fucose, sulfate, and sialic acid residues	558:598	fucose, sulfate, and sialic acid residues	558:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	0	37	theme	N-glycomic	119:128	arg1	features					130:137	both vertebrate and invertebrate N-glycomic features	86:137	both vertebrate and invertebrate N-glycomic features	86:137	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	3	38	theme	structures	656:665	arg1	diversity					630:638	diversity	630:638	diversity of carbohydrate structures within this phylum	630:684	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	39	theme	brittle	746:752	arg1	star					754:757	a brittle star	744:757	a brittle star (Ophiactis savignyi)	744:778	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	3	39	theme	brittle	746:752	arg1	Ophiactis					760:768	Ophiactis	760:768	Ophiactis	760:768	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	2	40	theme	fucose	558:563	arg1	residues					591:598	fucose, sulfate, and sialic acid residues	558:598	fucose, sulfate, and sialic acid residues	558:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	5	41	theme	complex	1039:1045	arg1	structures					1063:1072	hybrid and complex oligosaccharide structures	1028:1072	structures	1063:1072	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	0	42	gly	Glycosylation	0:12	arg2	nexus					33:37	an evolutionary nexus	17:37	an evolutionary nexus	17:37	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	2	43	theme	echinoderms	422:432	arg1	capacity					410:417	the N-glycomic capacity	395:417	the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues	395:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	2	44	theme	diverse	474:480	arg1	glycoconjugates					506:520	species-specific glycoconjugates	489:520	species-specific glycoconjugates	489:520	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	2	44	theme	diverse	474:480	arg1	ones					533:536	ones	533:536	ones heavily modified by fucose, sulfate, and sialic acid residues	533:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	2	44	theme	diverse	474:480	arg1	set					482:484	a diverse set	472:484	a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues	472:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	4	45	theme	exoglyosidase	904:916	arg1	treatments					931:940	various exoglyosidase and chemical treatments	896:940	various exoglyosidase and chemical treatments	896:940	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	5	46	theme	oligosaccharide	1047:1061	arg1	structures					1063:1072	hybrid and complex oligosaccharide structures	1028:1072	structures	1063:1072	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	1	47	theme	model	217:221	arg1	organisms					223:231	model organisms	217:231	model organisms	217:231	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	1	47	theme	model	217:221	arg1	Echinoderms					140:150	Echinoderms	140:150	Echinoderms	140:150	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	0	48	theme	brittle	44:50	arg1	savignyi					67:74	the brittle star Ophiactis savignyi	40:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi	0:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	1	49	theme	phylogenetic	321:332	arg1	group					334:338	this phylogenetic group	316:338	this phylogenetic group	316:338	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	2	50	theme	acid	586:589	arg1	residues					591:598	fucose, sulfate, and sialic acid residues	558:598	fucose, sulfate, and sialic acid residues	558:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	0	51	theme	star	52:55	arg1	savignyi					67:74	the brittle star Ophiactis savignyi	40:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi	0:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	1	52	used	used	209:212	arg2	organisms					223:231	model organisms	217:231	model organisms	217:231	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	1	52	used	used	209:212	arg2	Echinoderms					140:150	Echinoderms	140:150	Echinoderms	140:150	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32001617	5	53	theme	classical	1133:1141	arg1	structures					1163:1172	some classical invertebrate glycan structures	1128:1172	hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures	1028:1172	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	2	54	theme	sialic	579:584	arg1	acid					586:589	sialic acid	579:589	sialic acid	579:589	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	5	55	theme	invertebrate	1143:1154	arg1	structures					1163:1172	some classical invertebrate glycan structures	1128:1172	hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures	1028:1172	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	6	56	theme	N-glycans	1188:1196	arg1	%					1177:1177	70%	1175:1177	70% of these N-glycans	1175:1196	70% of these N-glycans were anionic, carrying either sialic acid, sulfate, or phosphate residues.
32001617	6	56	theme	N-glycans	1188:1196	arg1	N-glycans					1188:1196	these N-glycans	1182:1196	these N-glycans	1182:1196	70% of these N-glycans were anionic, carrying either sialic acid, sulfate, or phosphate residues.
32001617	3	57	theme	diversity	630:638	arg1	knowledge					617:625	the knowledge	613:625	the knowledge of diversity of carbohydrate structures within this phylum	613:684	To increase the knowledge of diversity of carbohydrate structures within this phylum, here we conducted an in-depth analysis of N-glycans from a brittle star (Ophiactis savignyi) as an example member of the class Ophiuroidea.
32001617	4	58	with	combination	945:955	arg1	MS/MS					979:983	MS/MS	979:983	MS/MS	979:983	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	4	58	with	combination	945:955	arg1	MS					972:973	MALDI-TOF MS	962:973	MALDI-TOF MS	962:973	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	0	59	theme	Ophiactis	57:65	arg1	savignyi					67:74	the brittle star Ophiactis savignyi	40:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi	0:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	4	60	theme	various	896:902	arg1	treatments					931:940	various exoglyosidase and chemical treatments	896:940	various exoglyosidase and chemical treatments	896:940	To this end, we performed a multi-step N-glycan analysis by HPLC and various exoglyosidase and chemical treatments in combination with MALDI-TOF MS and MS/MS.
32001617	2	61	theme	available	375:383	arg1	data					370:373	almost no data	360:373	almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues	360:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	5	62	theme	glycan	1156:1161	arg1	structures					1163:1172	some classical invertebrate glycan structures	1128:1172	hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures	1028:1172	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	2	63	theme	glycoconjugates	506:520	arg1	glycoconjugates					506:520	species-specific glycoconjugates	489:520	species-specific glycoconjugates	489:520	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	2	63	theme	glycoconjugates	506:520	arg1	ones					533:536	ones	533:536	ones heavily modified by fucose, sulfate, and sialic acid residues	533:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	2	63	theme	glycoconjugates	506:520	arg1	set					482:484	a diverse set	472:484	a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues	472:598	However, there are almost no data available regarding the N-glycomic capacity of echinoderms, which are otherwise known to produce a diverse set of species-specific glycoconjugates, including ones heavily modified by fucose, sulfate, and sialic acid residues.
32001617	5	64	theme	higher	1098:1103	arg1	vertebrates					1105:1115	higher vertebrates	1098:1115	higher vertebrates	1098:1115	Using this approach, we found a wealth of hybrid and complex oligosaccharide structures reminiscent of those in higher vertebrates as well as some classical invertebrate glycan structures.
32001617	0	65	dep	Glycosylation	0:12	arg1	savignyi					67:74	the brittle star Ophiactis savignyi	40:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi	0:74	Glycosylation at an evolutionary nexus: the brittle star Ophiactis savignyi expresses both vertebrate and invertebrate N-glycomic features.
32001617	1	66	theme	chordate	247:254	arg1	biology					256:262	chordate biology	247:262	chordate biology	247:262	Echinoderms are among the most primitive deuterostomes and have been used as model organisms to understand chordate biology because of their close evolutionary relationship to this phylogenetic group.
32888259	0	0	theme	N-linked	76:83	arg1	glycosylation					85:97	high mannose N-linked glycosylation	63:97	high mannose N-linked glycosylation	63:97	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	5	1	from	cells	1112:1116	arg1	inhibition					1079:1088	inhibition	1079:1088	inhibition	1079:1088	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	5	1	from	cells	1112:1116	arg1	binding					1067:1073	binding	1067:1073	binding	1067:1073	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	3	2	theme	culture	711:717	arg1	performance					719:729	cell culture performance	706:729	cell culture performance	706:729	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	1	3	theme	drug	272:275	arg1	safety					277:282	drug safety	272:282	drug safety	272:282	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	0	4	theme	mannose	68:74	arg1	glycosylation					85:97	high mannose N-linked glycosylation	63:97	high mannose N-linked glycosylation	63:97	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	1	5	gly	glycosylation	175:187	arg1	antibodies					215:224	therapeutic monoclonal antibodies	192:224	therapeutic monoclonal antibodies	192:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	1	6	theme	N-linked	166:173	arg1	attribute					258:266	an important product quality attribute	229:266	an important product quality attribute for drug safety and efficacy	229:295	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	1	6	theme	N-linked	166:173	arg1	glycosylation					175:187	N-linked glycosylation	166:187	N-linked glycosylation of therapeutic monoclonal antibodies	166:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	6	7	from	temperature	1230:1240	arg1	stable					1215:1220	stable	1215:1220	stable	1215:1220	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	4	8	dep	structure	942:950	arg1	2-amino-1,3-propanediol					953:975	2-amino-1,3-propanediol	953:975	2-amino-1,3-propanediol	953:975	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	6	9	theme	cost-effective	1195:1208	arg1	35x					1188:1190	35x	1188:1190	35x as cost-effective	1188:1208	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	6	9	theme	cost-effective	1195:1208	arg1	kifunensine					1175:1185	kifunensine	1175:1185	kifunensine	1175:1185	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	3	10	theme	chemical	537:544	arg1	additives					546:554	several chemical additives	529:554	several chemical additives	529:554	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	4	11	dep	inhibitors	845:854	arg1	bis-tris					863:870	bis-tris	863:870	bis-tris	863:870	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	11	dep	inhibitors	845:854	arg1	1-amino-1-methyl-1,3-propanediol					877:908	1-amino-1-methyl-1,3-propanediol	877:908	1-amino-1-methyl-1,3-propanediol	877:908	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	11	dep	inhibitors	845:854	arg1	tris					857:860	tris	857:860	tris	857:860	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	11	dep	inhibitors	845:854	arg1	inhibitors					845:854	novel inhibitors	839:854	known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol)	761:909	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	3	12	theme	cell	561:564	arg1	process					574:580	a cell culture process	559:580	a cell culture process	559:580	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	2	13	gly	glycosylation	414:426	arg1	drug					453:456	the innovator drug	439:456	the innovator drug	439:456	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	5	14	dep	binding	1067:1073	arg1	the					1063:1065	the	1063:1065	the	1063:1065	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	3	15	theme	additives	546:554	arg1	addition					517:524	the addition	513:524	the addition of several chemical additives to a cell culture process	513:580	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	7	16	from	glycosylation	1345:1357	arg1	production					1382:1391	monoclonal antibody production	1362:1391	monoclonal antibody production in a cell culture process	1362:1417	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	5	17	from	mannosidase	1093:1103	arg1	cells					1112:1116	CHO cells	1108:1116	CHO cells	1108:1116	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	0	18	theme	antibody	114:121	arg1	production					123:132	monoclonal antibody production	103:132	monoclonal antibody production in Chinese hamster ovary cells	103:163	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	7	19	theme	cell	1398:1401	arg1	process					1411:1417	a cell culture process	1396:1417	a cell culture process	1396:1417	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	7	20	theme	minimal	1424:1430	arg1	impact					1432:1437	minimal impact	1424:1437	minimal impact to productivity or cell health	1424:1468	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	3	21	from	N-glycans	607:615	arg1	antibodies					631:640	monoclonal antibodies	620:640	monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance	620:729	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	6	22	theme	inhibitors	1136:1145	arg1	One					1119:1121	One	1119:1121	One	1119:1121	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	6	22	theme	inhibitors	1136:1145	arg1	tris					1148:1151	tris	1148:1151	tris	1148:1151	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	6	22	theme	inhibitors	1136:1145	arg1	inhibitors					1136:1145	the novel inhibitors	1126:1145	the novel inhibitors	1126:1145	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	0	23	theme	monoclonal	103:112	arg1	production					123:132	monoclonal antibody production	103:132	monoclonal antibody production in Chinese hamster ovary cells	103:163	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	3	24	theme	cell	706:709	arg1	performance					719:729	cell culture performance	706:729	cell culture performance	706:729	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	4	25	theme	novel	839:843	arg1	bis-tris					863:870	bis-tris	863:870	bis-tris	863:870	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	25	theme	novel	839:843	arg1	1-amino-1-methyl-1,3-propanediol					877:908	1-amino-1-methyl-1,3-propanediol	877:908	1-amino-1-methyl-1,3-propanediol	877:908	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	25	theme	novel	839:843	arg1	tris					857:860	tris	857:860	tris	857:860	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	25	theme	novel	839:843	arg1	inhibitors					845:854	novel inhibitors	839:854	known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol)	761:909	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	3	26	theme	several	529:535	arg1	additives					546:554	several chemical additives	529:554	several chemical additives	529:554	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	7	27	theme	antibody	1373:1380	arg1	production					1382:1391	monoclonal antibody production	1362:1391	monoclonal antibody production in a cell culture process	1362:1417	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	2	28	theme	biosimilar	486:495	arg1	development					469:479	the development	465:479	the development of a biosimilar	465:495	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	2	29	theme	high	328:331	arg1	glycosylation					350:362	high mannose N-linked glycosylation	328:362	high mannose N-linked glycosylation	328:362	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	1	30	theme	therapeutic	192:202	arg1	antibodies					215:224	therapeutic monoclonal antibodies	192:224	therapeutic monoclonal antibodies	192:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	2	31	theme	drug	453:456	arg1	profile					428:434	the glycosylation profile	410:434	the glycosylation profile of the innovator drug	410:456	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	3	32	theme	culture	566:572	arg1	process					574:580	a cell culture process	559:580	a cell culture process	559:580	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	4	33	theme	known	761:765	arg1	deoxymannojirimycin					807:825	deoxymannojirimycin	807:825	deoxymannojirimycin	807:825	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	33	theme	known	761:765	arg1	kifunensine					791:801	kifunensine	791:801	kifunensine	791:801	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	33	theme	known	761:765	arg1	inhibitors					779:788	known mannosidase inhibitors	761:788	known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol)	761:909	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	1	34	theme	monoclonal	204:213	arg1	antibodies					215:224	therapeutic monoclonal antibodies	192:224	therapeutic monoclonal antibodies	192:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	0	35	theme	low-cost	11:18	arg1	alternatives					20:31	low-cost alternatives	11:31	low-cost alternatives to kifunensine	11:46	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	5	36	theme	shared	1015:1020	arg1	structure					1031:1039	The shared chemical structure	1011:1039	The shared chemical structure	1011:1039	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	4	37	theme	similar	924:930	arg1	structure					942:950	one similar molecular structure	920:950	one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol	920:1008	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	5	38	from	binding	1067:1073	arg1	cells					1112:1116	CHO cells	1108:1116	CHO cells	1108:1116	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	7	39	from	production	1382:1391	arg1	process					1411:1417	a cell culture process	1396:1417	a cell culture process	1396:1417	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	1	40	theme	antibodies	215:224	arg1	attribute					258:266	an important product quality attribute	229:266	an important product quality attribute for drug safety and efficacy	229:295	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	1	40	theme	antibodies	215:224	arg1	glycosylation					175:187	N-linked glycosylation	166:187	N-linked glycosylation of therapeutic monoclonal antibodies	166:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	7	41	gly	glycosylation	1345:1357	arg1	production					1382:1391	monoclonal antibody production	1362:1391	monoclonal antibody production in a cell culture process	1362:1417	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	1	42	link	N-linked	166:173	arg1	attribute					258:266	an important product quality attribute	229:266	an important product quality attribute for drug safety and efficacy	229:295	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	1	42	link	N-linked	166:173	arg1	glycosylation					175:187	N-linked glycosylation	166:187	N-linked glycosylation of therapeutic monoclonal antibodies	166:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	4	43	dep	inhibitors	779:788	arg1	deoxymannojirimycin					807:825	deoxymannojirimycin	807:825	deoxymannojirimycin	807:825	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	43	dep	inhibitors	779:788	arg1	kifunensine					791:801	kifunensine	791:801	kifunensine	791:801	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	43	dep	inhibitors	779:788	arg1	inhibitors					779:788	known mannosidase inhibitors	761:788	known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol)	761:909	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	7	44	theme	multiple	1282:1289	arg1	alternatives					1300:1311	multiple low-cost alternatives	1282:1311	multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health	1282:1468	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	4	45	contain	contain	912:918	arg2	structure					942:950	one similar molecular structure	920:950	one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol	920:1008	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	45	contain	contain	912:918	arg1	additives					736:744	The additives	732:744	The additives	732:744	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	0	46	theme	hamster	145:151	arg1	cells					159:163	Chinese hamster ovary cells	137:163	Chinese hamster ovary cells	137:163	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	3	47	theme	Chinese	654:660	arg1	cells					682:686	Chinese hamster ovary (CHO) cells	654:686	Chinese hamster ovary (CHO) cells	654:686	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	6	48	theme	room	1225:1228	arg1	temperature					1230:1240	room temperature	1225:1240	room temperature	1225:1240	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	2	49	theme	glycosylation	414:426	arg1	profile					428:434	the glycosylation profile	410:434	the glycosylation profile of the innovator drug	410:456	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	0	50	theme	alternatives	20:31	arg1	class					2:6	A class	0:6	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.	0:164	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	0	51	theme	Chinese	137:143	arg1	cells					159:163	Chinese hamster ovary cells	137:163	Chinese hamster ovary cells	137:163	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	2	52	theme	innovator	443:451	arg1	drug					453:456	the innovator drug	439:456	the innovator drug	439:456	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	0	53	link	N-linked	76:83	arg1	glycosylation					85:97	high mannose N-linked glycosylation	63:97	high mannose N-linked glycosylation	63:97	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	1	54	theme	important	232:240	arg1	attribute					258:266	an important product quality attribute	229:266	an important product quality attribute for drug safety and efficacy	229:295	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	1	54	theme	important	232:240	arg1	glycosylation					175:187	N-linked glycosylation	166:187	N-linked glycosylation of therapeutic monoclonal antibodies	166:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	5	55	theme	CHO	1108:1110	arg1	cells					1112:1116	CHO cells	1108:1116	CHO cells	1108:1116	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	7	56	theme	cell	1458:1461	arg1	health					1463:1468	cell health	1458:1468	cell health	1458:1468	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	6	57	theme	novel	1130:1134	arg1	inhibitors					1136:1145	the novel inhibitors	1126:1145	the novel inhibitors	1126:1145	One of the novel inhibitors, tris, is safer compared to kifunensine, 35x as cost-effective, and stable at room temperature.
32888259	4	58	theme	molecular	932:940	arg1	structure					942:950	one similar molecular structure	920:950	one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol	920:1008	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	0	59	theme	ovary	153:157	arg1	cells					159:163	Chinese hamster ovary cells	137:163	Chinese hamster ovary cells	137:163	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	2	60	theme	glycosylation	350:362	arg1	percent					317:323	the percent	313:323	the percent of high mannose N-linked glycosylation	313:362	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	3	61	theme	CHO	677:679	arg1	cells					682:686	Chinese hamster ovary (CHO) cells	654:686	Chinese hamster ovary (CHO) cells	654:686	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	7	62	theme	monoclonal	1362:1371	arg1	production					1382:1391	monoclonal antibody production	1362:1391	monoclonal antibody production in a cell culture process	1362:1417	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	3	63	theme	high	594:597	arg1	N-glycans					607:615	high mannose N-glycans	594:615	high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance	594:729	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	2	64	theme	N-linked	341:348	arg1	glycosylation					350:362	high mannose N-linked glycosylation	328:362	high mannose N-linked glycosylation	328:362	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	7	65	theme	culture	1403:1409	arg1	process					1411:1417	a cell culture process	1396:1417	a cell culture process	1396:1417	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	1	66	theme	product	242:248	arg1	attribute					258:266	an important product quality attribute	229:266	an important product quality attribute for drug safety and efficacy	229:295	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	1	66	theme	product	242:248	arg1	glycosylation					175:187	N-linked glycosylation	166:187	N-linked glycosylation of therapeutic monoclonal antibodies	166:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	4	67	theme	mannosidase	767:777	arg1	deoxymannojirimycin					807:825	deoxymannojirimycin	807:825	deoxymannojirimycin	807:825	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	67	theme	mannosidase	767:777	arg1	kifunensine					791:801	kifunensine	791:801	kifunensine	791:801	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	4	67	theme	mannosidase	767:777	arg1	inhibitors					779:788	known mannosidase inhibitors	761:788	known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol)	761:909	The additives, which include known mannosidase inhibitors (kifunensine and deoxymannojirimycin) as well as novel inhibitors (tris, bis-tris, and 1-amino-1-methyl-1,3-propanediol), contain one similar molecular structure: 2-amino-1,3-propanediol, commonly referred to as serinol.
32888259	3	68	theme	hamster	662:668	arg1	cells					682:686	Chinese hamster ovary (CHO) cells	654:686	Chinese hamster ovary (CHO) cells	654:686	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	3	69	theme	monoclonal	620:629	arg1	antibodies					631:640	monoclonal antibodies	620:640	monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance	620:729	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	5	70	theme	mannosidase	1093:1103	arg1	inhibition					1079:1088	inhibition	1079:1088	inhibition	1079:1088	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	5	70	theme	mannosidase	1093:1103	arg1	binding					1067:1073	binding	1067:1073	binding	1067:1073	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	2	71	theme	mannose	333:339	arg1	glycosylation					350:362	high mannose N-linked glycosylation	328:362	high mannose N-linked glycosylation	328:362	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	1	72	theme	quality	250:256	arg1	attribute					258:266	an important product quality attribute	229:266	an important product quality attribute for drug safety and efficacy	229:295	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	1	72	theme	quality	250:256	arg1	glycosylation					175:187	N-linked glycosylation	166:187	N-linked glycosylation of therapeutic monoclonal antibodies	166:224	N-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy.
32888259	0	73	theme	high	63:66	arg1	glycosylation					85:97	high mannose N-linked glycosylation	63:97	high mannose N-linked glycosylation	63:97	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
32888259	3	74	theme	ovary	670:674	arg1	cells					682:686	Chinese hamster ovary (CHO) cells	654:686	Chinese hamster ovary (CHO) cells	654:686	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	3	75	theme	mannose	599:605	arg1	N-glycans					607:615	high mannose N-glycans	594:615	high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance	594:729	In this study, the addition of several chemical additives to a cell culture process resulted in high mannose N-glycans on monoclonal antibodies produced by Chinese hamster ovary (CHO) cells without impacting cell culture performance.
32888259	7	76	theme	low-cost	1291:1298	arg1	alternatives					1300:1311	multiple low-cost alternatives	1282:1311	multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health	1282:1468	In addition, tris and bis-tris provide multiple low-cost alternatives to kifunensine for manipulating glycosylation in monoclonal antibody production in a cell culture process with minimal impact to productivity or cell health.
32888259	2	77	theme	drug	384:387	arg1	efficacy					389:396	drug efficacy	384:396	drug efficacy	384:396	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	2	78	from	increase	301:308	arg1	percent					317:323	the percent	313:323	the percent of high mannose N-linked glycosylation	313:362	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	5	79	from	inhibition	1079:1088	arg1	cells					1112:1116	CHO cells	1108:1116	CHO cells	1108:1116	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	2	80	link	N-linked	341:348	arg1	glycosylation					350:362	high mannose N-linked glycosylation	328:362	high mannose N-linked glycosylation	328:362	An increase in the percent of high mannose N-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar.
32888259	5	81	theme	chemical	1022:1029	arg1	structure					1031:1039	The shared chemical structure	1011:1039	The shared chemical structure	1011:1039	The shared chemical structure provides insight into the binding and inhibition of mannosidase in CHO cells.
32888259	0	82	from	production	123:132	arg1	cells					159:163	Chinese hamster ovary cells	137:163	Chinese hamster ovary cells	137:163	A class of low-cost alternatives to kifunensine for increasing high mannose N-linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells.
34089345	1	0	theme	glycoprotein	295:306	arg1	ligands					308:314	the endogenous glycan and glycoprotein ligands	269:314	ligands	308:314	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	9	1	contain	contained	1411:1419	arg2	N-glycans					1444:1452	oligomannose N-glycans	1431:1452	oligomannose N-glycans	1431:1452	All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results.
34089345	9	1	contain	contained	1411:1419	arg1	glycoproteins					1367:1379	All enriched glycoproteins	1354:1379	All enriched glycoproteins	1354:1379	All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results.
34089345	9	1	contain	contained	1411:1419	arg2	pauci-					1421:1426	pauci-	1421:1426	pauci-	1421:1426	All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results.
34089345	5	2	from	presence	805:812	arg1	surface					832:838	the surface	828:838	the surface of cancer cells	828:854	We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry.
34089345	8	3	theme	cell	1190:1193	arg1	A549					1200:1203	the lung cancer cell line A549	1174:1203	the lung cancer cell line A549	1174:1203	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	10	4	theme	oligomannosidic	1568:1582	arg1	structures					1595:1604	structures	1595:1604	structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology	1595:1701	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	10	4	theme	oligomannosidic	1568:1582	arg1	N-glycans					1584:1592	oligomannosidic N-glycans	1568:1592	oligomannosidic N-glycans	1568:1592	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	7	5	theme	MR	1035:1036	arg1	selective					1048:1056	selective	1048:1056	selective	1048:1056	Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested.
34089345	7	5	theme	MR	1035:1036	arg1	CTLD4-7					1020:1026	the CTLD4-7	1016:1026	the CTLD4-7 of the MR	1016:1036	Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested.
34089345	8	6	theme	MR-Fc	1220:1224	arg1	binding					1226:1232	intense MR-Fc binding	1212:1232	intense MR-Fc binding	1212:1232	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	5	7	attach	presence	805:812	arg2	ligands					817:823	ligands	817:823	ligands	817:823	We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry.
34089345	5	7	attach	presence	805:812	arg1	surface					832:838	the surface	828:838	the surface of cancer cells	828:854	We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry.
34089345	2	8	theme	IgG	461:463	arg1	Fc-portion					441:450	the Fc-portion	437:450	the Fc-portion of human IgG (MR-Fc)	437:471	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	2	9	theme	glycoprotein	506:517	arg1	recognition					519:529	the MR glycan and glycoprotein recognition	488:529	recognition	519:529	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	4	10	theme	surface-located	763:777	arg1	ligands					733:739	MR-Fc ligands	727:739	MR-Fc ligands	727:739	All cancer tissues and several control tissues exhibited MR-Fc ligands, intracellular and/or surface-located.
34089345	0	11	gly	glycoproteins	60:72	arg1	glycoproteins					60:72	glycoproteins	60:72	glycoproteins recognized by the mannose receptor (CD206)	60:115	Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206).
34089345	6	12	theme	MR	919:920	arg1	specificity					900:910	the fine specificity	891:910	the fine specificity of the MR for glycans	891:932	To characterize the fine specificity of the MR for glycans, we screened a panel of glycan microarrays.
34089345	0	13	theme	mannose	92:98	arg1	receptor					100:107	mannose receptor	92:107	the mannose receptor (CD206)	88:115	Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206).
34089345	0	13	theme	mannose	92:98	arg1	CD206					110:114	CD206	110:114	CD206	110:114	Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206).
34089345	10	14	theme	potential	1660:1668	arg1	role					1670:1673	a potential role	1658:1673	a potential role for the MR in tumor biology	1658:1701	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	8	15	theme	cancer	1183:1188	arg1	A549					1200:1203	the lung cancer cell line A549	1174:1203	the lung cancer cell line A549	1174:1203	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	1	16	gly	glycoprotein	295:306	arg1	glycoprotein					295:306	the endogenous glycan and glycoprotein ligands	269:314	glycoprotein	295:306	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	5	17	theme	flow	859:862	arg1	cytometry					864:872	flow cytometry	859:872	flow cytometry	859:872	We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry.
34089345	0	18	from	N-glycans	47:55	arg1	glycoproteins					60:72	glycoproteins	60:72	glycoproteins recognized by the mannose receptor (CD206)	60:115	Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206).
34089345	6	19	theme	glycan	958:963	arg1	microarrays					965:975	glycan microarrays	958:975	glycan microarrays	958:975	To characterize the fine specificity of the MR for glycans, we screened a panel of glycan microarrays.
34089345	4	20	theme	control	701:707	arg1	tissues					709:715	several control tissues	693:715	several control tissues	693:715	All cancer tissues and several control tissues exhibited MR-Fc ligands, intracellular and/or surface-located.
34089345	9	21	theme	enriched	1358:1365	arg1	glycoproteins					1367:1379	All enriched glycoproteins	1354:1379	All enriched glycoproteins	1354:1379	All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results.
34089345	10	22	theme	tumor	1633:1637	arg1	cells					1639:1643	tumor cells	1633:1643	tumor cells	1633:1643	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	7	23	theme	oligomannose	1091:1102	arg1	N-glycans					1104:1112	oligomannose N-glycans	1091:1112	oligomannose N-glycans	1091:1112	Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested.
34089345	1	24	theme	C-type	334:339	arg1	domains					348:354	its C-type lectin domains	330:354	its C-type lectin domains (CTLD)	330:361	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	2	25	theme	MR	415:416	arg1	CTLD4-7					418:424	the murine MR CTLD4-7	404:424	the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc)	404:471	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	4	26	theme	several	693:699	arg1	tissues					709:715	several control tissues	693:715	several control tissues	693:715	All cancer tissues and several control tissues exhibited MR-Fc ligands, intracellular and/or surface-located.
34089345	8	27	theme	intense	1212:1218	arg1	binding					1226:1232	intense MR-Fc binding	1212:1232	intense MR-Fc binding	1212:1232	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	8	28	gly	glycoprotein	1266:1277	arg1	glycoprotein					1266:1277	the MR glycoprotein ligands	1259:1285	the MR glycoprotein ligands	1259:1285	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	9	29	theme	oligomannose	1431:1442	arg1	N-glycans					1444:1452	oligomannose N-glycans	1431:1452	oligomannose N-glycans	1431:1452	All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results.
34089345	1	30	theme	lectin	341:346	arg1	domains					348:354	its C-type lectin domains	330:354	its C-type lectin domains (CTLD)	330:361	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	8	31	theme	MR	1263:1264	arg1	ligands					1279:1285	the MR glycoprotein ligands	1259:1285	the MR glycoprotein ligands	1259:1285	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	2	32	theme	MR	492:493	arg1	glycan					495:500	the MR glycan and glycoprotein recognition	488:529	glycan	495:500	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	8	33	theme	cancer	1156:1161	arg1	tissue					1163:1168	lung cancer tissue	1151:1168	lung cancer tissue	1151:1168	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	0	34	theme	Tumor	0:4	arg1	cells					6:10	Tumor cells	0:10	Tumor cells	0:10	Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206).
34089345	1	35	theme	innate	243:248	arg1	immunity					250:257	innate immunity	243:257	innate immunity	243:257	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	36	dep	CD206	151:155	arg1	MR					158:159	MR	158:159	MR	158:159	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	5	37	theme	ligands	817:823	arg1	presence					805:812	the presence	801:812	the presence of ligands on the surface of cancer cells	801:854	We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry.
34089345	7	38	theme	specific	1062:1069	arg1	types					1071:1075	specific types	1062:1075	specific types of pauci- and oligomannose N-glycans	1062:1112	Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested.
34089345	10	39	from	role	1670:1673	arg1	biology					1695:1701	tumor biology	1689:1701	tumor biology	1689:1701	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	8	40	theme	line	1195:1198	arg1	A549					1200:1203	the lung cancer cell line A549	1174:1203	the lung cancer cell line A549	1174:1203	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	4	41	theme	cancer	674:679	arg1	tissues					681:687	All cancer tissues	670:687	All cancer tissues	670:687	All cancer tissues and several control tissues exhibited MR-Fc ligands, intracellular and/or surface-located.
34089345	6	42	theme	microarrays	965:975	arg1	panel					949:953	a panel	947:953	a panel of glycan microarrays	947:975	To characterize the fine specificity of the MR for glycans, we screened a panel of glycan microarrays.
34089345	6	43	theme	fine	895:898	arg1	specificity					900:910	the fine specificity	891:910	the fine specificity of the MR for glycans	891:932	To characterize the fine specificity of the MR for glycans, we screened a panel of glycan microarrays.
34089345	3	44	theme	control	566:572	arg1	tissues					574:580	16 different cancer and control tissues	542:580	tissues	574:580	We probed 16 different cancer and control tissues using the MR-Fc, and observed cell- and tissue-specific binding with varying intensity.
34089345	8	45	theme	glycoprotein	1266:1277	arg1	ligands					1279:1285	the MR glycoprotein ligands	1259:1285	the MR glycoprotein ligands	1259:1285	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	1	46	theme	endocytic	168:176	arg1	receptor					141:148	The macrophage mannose receptor	118:148	The macrophage mannose receptor (CD206, MR)	118:160	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	46	theme	endocytic	168:176	arg1	receptor					185:192	an endocytic lectin receptor	165:192	an endocytic lectin receptor which plays an important role in homeostasis and innate immunity	165:257	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	0	47	theme	oligomannosidic	31:45	arg1	N-glycans					47:55	oligomannosidic N-glycans	31:55	oligomannosidic N-glycans	31:55	Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206).
34089345	5	48	theme	cells	850:854	arg1	surface					832:838	the surface	828:838	the surface of cancer cells	828:854	We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry.
34089345	7	49	theme	pauci-	1080:1085	arg1	types					1071:1075	specific types	1062:1075	specific types of pauci- and oligomannose N-glycans	1062:1112	Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested.
34089345	4	50	theme	intracellular	742:754	arg1	ligands					733:739	MR-Fc ligands	727:739	MR-Fc ligands	727:739	All cancer tissues and several control tissues exhibited MR-Fc ligands, intracellular and/or surface-located.
34089345	8	51	theme	lung	1151:1154	arg1	tissue					1163:1168	lung cancer tissue	1151:1168	lung cancer tissue	1151:1168	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	1	52	theme	lectin	178:183	arg1	receptor					141:148	The macrophage mannose receptor	118:148	The macrophage mannose receptor (CD206, MR)	118:160	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	52	theme	lectin	178:183	arg1	receptor					185:192	an endocytic lectin receptor	165:192	an endocytic lectin receptor which plays an important role in homeostasis and innate immunity	165:257	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	2	53	theme	murine	408:413	arg1	CTLD4-7					418:424	the murine MR CTLD4-7	404:424	the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc)	404:471	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	8	54	theme	lung	1178:1181	arg1	A549					1200:1203	the lung cancer cell line A549	1174:1203	the lung cancer cell line A549	1174:1203	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	2	55	gly	glycoprotein	506:517	arg1	glycoprotein					506:517	the MR glycan and glycoprotein recognition	488:529	glycoprotein	506:517	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	7	56	theme	N-glycans	1104:1112	arg1	types					1071:1075	specific types	1062:1075	specific types of pauci- and oligomannose N-glycans	1062:1112	Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested.
34089345	2	57	theme	human	455:459	arg1	MR-Fc					466:470	MR-Fc	466:470	MR-Fc	466:470	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	2	57	theme	human	455:459	arg1	IgG					461:463	human IgG	455:463	human IgG (MR-Fc)	455:471	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	3	58	theme	tissue-specific	622:636	arg1	binding					638:644	cell- and tissue-specific binding	612:644	cell- and tissue-specific binding	612:644	We probed 16 different cancer and control tissues using the MR-Fc, and observed cell- and tissue-specific binding with varying intensity.
34089345	5	59	theme	cancer	843:848	arg1	cells					850:854	cancer cells	843:854	cancer cells	843:854	We further confirmed the presence of ligands on the surface of cancer cells by flow cytometry.
34089345	1	60	theme	endogenous	273:282	arg1	glycan					284:289	the endogenous glycan and glycoprotein ligands	269:314	glycan	284:289	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	0	61	from	pauci-	20:25	arg1	glycoproteins					60:72	glycoproteins	60:72	glycoproteins recognized by the mannose receptor (CD206)	60:115	Tumor cells express pauci- and oligomannosidic N-glycans in glycoproteins recognized by the mannose receptor (CD206).
34089345	10	62	theme	tumor	1689:1693	arg1	biology					1695:1701	tumor biology	1689:1701	tumor biology	1689:1701	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	3	63	theme	cell-	612:616	arg1	binding					638:644	cell- and tissue-specific binding	612:644	cell- and tissue-specific binding	612:644	We probed 16 different cancer and control tissues using the MR-Fc, and observed cell- and tissue-specific binding with varying intensity.
34089345	8	64	theme	glycoproteomic	1329:1342	arg1	analysis					1344:1351	glycoproteomic analysis	1329:1351	glycoproteomic analysis	1329:1351	As lung cancer tissue and the lung cancer cell line A549 showed intense MR-Fc binding, we further investigated the MR glycoprotein ligands in those cells by immunoprecipitation and glycoproteomic analysis.
34089345	9	65	theme	microarray	1470:1479	arg1	results					1481:1487	the microarray results	1466:1487	the microarray results	1466:1487	All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results.
34089345	3	66	theme	different	545:553	arg1	cancer					555:560	16 different cancer and control tissues	542:580	cancer	555:560	We probed 16 different cancer and control tissues using the MR-Fc, and observed cell- and tissue-specific binding with varying intensity.
34089345	1	67	theme	macrophage	122:131	arg1	receptor					141:148	The macrophage mannose receptor	118:148	The macrophage mannose receptor (CD206, MR)	118:160	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	67	theme	macrophage	122:131	arg1	receptor					185:192	an endocytic lectin receptor	165:192	an endocytic lectin receptor which plays an important role in homeostasis and innate immunity	165:257	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	67	theme	macrophage	122:131	arg1	CD206					151:155	CD206	151:155	CD206	151:155	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	9	68	gly	glycoproteins	1367:1379	arg1	glycoproteins					1367:1379	All enriched glycoproteins	1354:1379	All enriched glycoproteins	1354:1379	All enriched glycoproteins, of which 42 were identified, contained pauci- or oligomannose N-glycans, confirming the microarray results.
34089345	7	69	theme	glycans	1132:1138	arg1	hundreds					1120:1127	hundreds	1120:1127	hundreds of glycans tested	1120:1145	Remarkably, the results indicate that the CTLD4-7 of the MR is highly selective for specific types of pauci- and oligomannose N-glycans among hundreds of glycans tested.
34089345	1	70	theme	mannose	133:139	arg1	receptor					141:148	The macrophage mannose receptor	118:148	The macrophage mannose receptor (CD206, MR)	118:160	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	70	theme	mannose	133:139	arg1	receptor					185:192	an endocytic lectin receptor	165:192	an endocytic lectin receptor which plays an important role in homeostasis and innate immunity	165:257	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	70	theme	mannose	133:139	arg1	CD206					151:155	CD206	151:155	CD206	151:155	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	1	71	dep	domains	348:354	arg1	CTLD					357:360	CTLD	357:360	CTLD	357:360	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34089345	2	72	used	used	399:402	arg2	we					396:397	we	396:397	we	396:397	Here we used the murine MR CTLD4-7 coupled to the Fc-portion of human IgG (MR-Fc) to investigate the MR glycan and glycoprotein recognition.
34089345	4	73	theme	MR-Fc	727:731	arg1	ligands					733:739	MR-Fc ligands	727:739	MR-Fc ligands	727:739	All cancer tissues and several control tissues exhibited MR-Fc ligands, intracellular and/or surface-located.
34089345	10	74	theme	MR	1522:1523	arg1	CTLD4-7					1525:1531	the MR CTLD4-7	1518:1531	the MR CTLD4-7	1518:1531	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	10	74	theme	MR	1522:1523	arg1	selective					1543:1551	selective	1543:1551	selective	1543:1551	Our study demonstrates that the MR CTLD4-7 is highly selective for pauci- and oligomannosidic N-glycans, structures that are often elevated in tumor cells, and suggest a potential role for the MR in tumor biology.
34089345	1	75	theme	important	209:217	arg1	role					219:222	an important role	206:222	an important role	206:222	The macrophage mannose receptor (CD206, MR) is an endocytic lectin receptor which plays an important role in homeostasis and innate immunity, however, the endogenous glycan and glycoprotein ligands recognized by its C-type lectin domains (CTLD) have not been well studied.
34210959	4	0	theme	glycoside	977:985	arg1	hydrolases					987:996	glycoside hydrolases	977:996	glycoside hydrolases	977:996	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	1	with	interface	834:842	arg1	microorganisms					860:873	pathogenic microorganisms	849:873	pathogenic microorganisms	849:873	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	2	2	theme	mucins	454:459	arg1	content					443:449	the informational content	425:449	the informational content of mucins	425:459	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	4	3	theme	pathogenic	849:858	arg1	microorganisms					860:873	pathogenic microorganisms	849:873	pathogenic microorganisms	849:873	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	4	with	interactions	1034:1045	arg1	TRs					1058:1060	mucin TRs	1052:1060	mucin TRs	1052:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	5	theme	experimental	772:783	arg1	studies					785:791	experimental studies	772:791	experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome	772:892	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	3	6	theme	secreted	653:660	arg1	reporters					662:670	membrane-bound and secreted reporters	634:670	membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells	634:712	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	4	7	theme	mucins	820:825	arg1	role					812:815	the versatile role	798:815	the versatile role of mucins at the interface with pathogenic microorganisms	798:873	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	7	theme	mucins	820:825	arg1	microbiome					883:892	the microbiome	879:892	the microbiome	879:892	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	2	8	theme	variable	271:278	arg1	domains					299:305	their variable tandem repeat (TR) domains	265:305	their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns	265:388	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	3	9	theme	HEK293	701:706	arg1	cells					708:712	glycoengineered HEK293 cells	685:712	glycoengineered HEK293 cells	685:712	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	4	10	theme	viruses	1016:1022	arg1	roles					958:962	specific roles	949:962	specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	949:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	11	theme	mucin	739:743	arg1	advances					763:770	defined mucin TR O-glycodomains advances	731:770	defined mucin TR O-glycodomains advances	731:770	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	12	theme	hydrolases	987:996	arg1	roles					958:962	specific roles	949:962	specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	949:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	3	13	dep	display	509:515	arg1	the					505:507	the	505:507	the	505:507	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	4	14	theme	roles	958:962	arg1	dissection					935:944	molecular dissection	925:944	molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	925:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	15	from	interface	834:842	arg1	role					812:815	the versatile role	798:815	the versatile role of mucins at the interface with pathogenic microorganisms	798:873	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	15	from	interface	834:842	arg1	microbiome					883:892	the microbiome	879:892	the microbiome	879:892	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	16	with	viruses	1016:1022	arg1	TRs					1058:1060	mucin TRs	1052:1060	mucin TRs	1052:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	17	theme	advances	763:770	arg1	Availability					715:726	Availability	715:726	Availability of defined mucin TR O-glycodomains advances	715:770	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	2	18	theme	distinct	372:379	arg1	patterns					381:388	distinct patterns	372:388	distinct patterns	372:388	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	3	19	with	display	509:515	arg1	patterns					606:613	patterns	606:613	patterns	606:613	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	19	with	display	509:515	arg1	structures					591:600	tunable structures	583:600	tunable structures	583:600	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	4	20	theme	O-glycodomains	748:761	arg1	advances					763:770	defined mucin TR O-glycodomains advances	731:770	defined mucin TR O-glycodomains advances	731:770	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	1	21	theme	mucosal	155:161	arg1	surfaces					163:170	all mucosal surfaces	151:170	all mucosal surfaces	151:170	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	3	22	theme	glycoengineered	685:699	arg1	cells					708:712	glycoengineered HEK293 cells	685:712	glycoengineered HEK293 cells	685:712	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	4	23	with	glycopeptidases	999:1013	arg1	TRs					1058:1060	mucin TRs	1052:1060	mucin TRs	1052:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	24	dep	studies	785:791	arg1	Availability					715:726	Availability	715:726	Availability of defined mucin TR O-glycodomains advances	715:770	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	3	25	with	production	521:530	arg1	patterns					606:613	patterns	606:613	patterns	606:613	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	25	with	production	521:530	arg1	structures					591:600	tunable structures	583:600	tunable structures	583:600	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	26	theme	human	535:539	arg1	acids					571:575	~200 amino acids	560:575	~200 amino acids	560:575	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	26	theme	human	535:539	arg1	O-glycodomains					544:557	human TR O-glycodomains	535:557	human TR O-glycodomains (~200 amino acids)	535:576	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	2	27	theme	O-glycan	349:356	arg1	structures					358:367	different O-glycan structures	339:367	different O-glycan structures in distinct patterns	339:388	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	0	28	theme	human	15:19	arg1	mucinome					21:28	the human mucinome	11:28	the human mucinome	11:28	Display of the human mucinome with defined O-glycans by gene engineered cells.
34210959	4	29	with	hydrolases	987:996	arg1	TRs					1058:1060	mucin TRs	1052:1060	mucin TRs	1052:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	2	30	theme	repeat	287:292	arg1	domains					299:305	their variable tandem repeat (TR) domains	265:305	their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns	265:388	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	4	31	theme	other	1028:1032	arg1	interactions					1034:1045	other interactions	1028:1045	other interactions with mucin TRs	1028:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	32	theme	new	906:908	arg1	strategies					910:919	new strategies	906:919	new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	906:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	2	33	theme	tandem	280:285	arg1	repeat					287:292	tandem repeat	280:292	their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns	265:388	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	2	33	theme	tandem	280:285	arg1	TR					295:296	TR	295:296	TR	295:296	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	1	34	theme	O-glycosylated	116:129	arg1	proteins					131:138	heavily O-glycosylated proteins	108:138	heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids	108:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	4	35	theme	molecular	925:933	arg1	dissection					935:944	molecular dissection	925:944	molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	925:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	1	36	theme	major	191:195	arg1	macromolecules					197:210	the major macromolecules	187:210	the major macromolecules in most body fluids	187:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	2	37	theme	content	443:449	arg1	much					417:420	much	417:420	much	417:420	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	4	38	theme	glycopeptidases	999:1013	arg1	roles					958:962	specific roles	949:962	specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	949:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	0	39	theme	mucinome	21:28	arg1	Display					0:6	Display	0:6	Display of the human mucinome with defined O-glycans by gene	0:59	Display of the human mucinome with defined O-glycans by gene engineered cells.
34210959	3	40	theme	tunable	583:589	arg1	structures					591:600	tunable structures	583:600	tunable structures	583:600	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	4	41	theme	interactions	1034:1045	arg1	roles					958:962	specific roles	949:962	specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	949:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	2	42	from	structures	358:367	arg1	patterns					381:388	distinct patterns	372:388	distinct patterns	372:388	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	4	43	theme	specific	949:956	arg1	roles					958:962	specific roles	949:962	specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	949:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	2	44	theme	informational	429:441	arg1	content					443:449	the informational content	425:449	the informational content of mucins	425:459	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	3	45	theme	TR	541:542	arg1	acids					571:575	~200 amino acids	560:575	~200 amino acids	560:575	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	45	theme	TR	541:542	arg1	O-glycodomains					544:557	human TR O-glycodomains	535:557	human TR O-glycodomains (~200 amino acids)	535:576	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	1	46	from	macromolecules	197:210	arg1	fluids					225:230	most body fluids	215:230	most body fluids	215:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	1	47	theme	large	92:96	arg1	Mucins					79:84	Mucins	79:84	Mucins	79:84	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	1	47	theme	large	92:96	arg1	family					98:103	a large family	90:103	a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids	90:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	0	48	theme	defined	35:41	arg1	O-glycans					43:51	defined O-glycans	35:51	defined O-glycans	35:51	Display of the human mucinome with defined O-glycans by gene engineered cells.
34210959	1	49	gly	O-glycosylated	116:129	arg1	proteins					131:138	heavily O-glycosylated proteins	108:138	heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids	108:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	3	50	theme	O-glycodomains	544:557	arg1	production					521:530	production	521:530	production	521:530	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	50	theme	O-glycodomains	544:557	arg1	display					509:515	display	509:515	display	509:515	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	4	51	with	adhesins	967:974	arg1	TRs					1058:1060	mucin TRs	1052:1060	mucin TRs	1052:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	52	theme	versatile	802:810	arg1	role					812:815	the versatile role	798:815	the versatile role of mucins at the interface with pathogenic microorganisms	798:873	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	3	53	theme	membrane-bound	634:647	arg1	reporters					662:670	membrane-bound and secreted reporters	634:670	membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells	634:712	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	0	54	with	Display	0:6	arg1	O-glycans					43:51	defined O-glycans	35:51	defined O-glycans	35:51	Display of the human mucinome with defined O-glycans by gene engineered cells.
34210959	4	55	theme	defined	731:737	arg1	advances					763:770	defined mucin TR O-glycodomains advances	731:770	defined mucin TR O-glycodomains advances	731:770	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	4	56	theme	TR	745:746	arg1	advances					763:770	defined mucin TR O-glycodomains advances	731:770	defined mucin TR O-glycodomains advances	731:770	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	3	57	theme	cell-based	481:490	arg1	platform					492:499	a cell-based platform	479:499	a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells	479:712	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	1	58	theme	most	215:218	arg1	fluids					225:230	most body fluids	215:230	most body fluids	215:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	4	59	theme	adhesins	967:974	arg1	roles					958:962	specific roles	949:962	specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs	949:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
34210959	3	60	theme	O-glycans	618:626	arg1	patterns					606:613	patterns	606:613	patterns	606:613	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	60	theme	O-glycans	618:626	arg1	structures					591:600	tunable structures	583:600	tunable structures	583:600	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	61	theme	amino	565:569	arg1	acids					571:575	~200 amino acids	560:575	~200 amino acids	560:575	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	3	61	theme	amino	565:569	arg1	O-glycodomains					544:557	human TR O-glycodomains	535:557	human TR O-glycodomains (~200 amino acids)	535:576	Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.
34210959	2	62	theme	different	339:347	arg1	structures					358:367	different O-glycan structures	339:367	different O-glycan structures in distinct patterns	339:388	Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins.
34210959	1	63	theme	body	220:223	arg1	fluids					225:230	most body fluids	215:230	most body fluids	215:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	1	64	theme	proteins	131:138	arg1	Mucins					79:84	Mucins	79:84	Mucins	79:84	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	1	64	theme	proteins	131:138	arg1	family					98:103	a large family	90:103	a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids	90:230	Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids.
34210959	4	65	theme	mucin	1052:1056	arg1	TRs					1058:1060	mucin TRs	1052:1060	mucin TRs	1052:1060	Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.
32334683	0	0	theme	monoclonal	80:89	arg1	antibodies					91:100	therapeutic monoclonal antibodies	68:100	therapeutic monoclonal antibodies	68:100	FTIR spectroscopy as an analytical tool to compare glycosylation in therapeutic monoclonal antibodies.
32334683	8	1	gly	glycoproteins	1319:1331	arg1	glycoproteins					1319:1331	glycoproteins	1319:1331	glycoproteins	1319:1331	We show that FTIR spectra of glycoproteins provide a global but accurate fingerprint of the glycosylation profile.
32334683	8	2	theme	glycoproteins	1319:1331	arg1	spectra					1308:1314	FTIR spectra	1303:1314	FTIR spectra of glycoproteins	1303:1331	We show that FTIR spectra of glycoproteins provide a global but accurate fingerprint of the glycosylation profile.
32334683	0	3	theme	therapeutic	68:78	arg1	antibodies					91:100	therapeutic monoclonal antibodies	68:100	therapeutic monoclonal antibodies	68:100	FTIR spectroscopy as an analytical tool to compare glycosylation in therapeutic monoclonal antibodies.
32334683	6	4	theme	profile	829:835	arg1	terms					788:792	terms	788:792	terms of glycosylation or monosaccharide profile	788:835	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	4	5	theme	direct	572:577	arg1	method					590:595	orthogonal, direct and simple method	560:595	orthogonal, direct and simple method	560:595	The development of orthogonal, direct and simple method is therefore desirable.
32334683	7	6	theme	FTIR	1173:1176	arg1	spectra					1178:1184	FTIR spectra	1173:1184	FTIR spectra of glycoproteins	1173:1201	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	9	7	dep	presence	1477:1484	arg1	the					1473:1475	the	1473:1475	the	1473:1475	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	0	8	gly	glycosylation	51:63	arg1	antibodies					91:100	therapeutic monoclonal antibodies	68:100	therapeutic monoclonal antibodies	68:100	FTIR spectroscopy as an analytical tool to compare glycosylation in therapeutic monoclonal antibodies.
32334683	6	9	gly	glycosylation	883:895	arg1	biosimilar					902:911	a biosimilar	900:911	a biosimilar	900:911	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	4	10	theme	method	590:595	arg1	desirable					610:618	desirable	610:618	desirable	610:618	The development of orthogonal, direct and simple method is therefore desirable.
32334683	4	10	theme	method	590:595	arg1	development					545:555	The development	541:555	The development of orthogonal, direct and simple method	541:595	The development of orthogonal, direct and simple method is therefore desirable.
32334683	9	11	theme	several	1500:1506	arg1	monosaccharides					1508:1522	several monosaccharides	1500:1522	several monosaccharides	1500:1522	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	7	12	theme	Fc-fusion	1081:1089	arg1	protein					1091:1097	one Fc-fusion protein	1077:1097	one Fc-fusion protein	1077:1097	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	4	13	theme	simple	583:588	arg1	method					590:595	orthogonal, direct and simple method	560:595	orthogonal, direct and simple method	560:595	The development of orthogonal, direct and simple method is therefore desirable.
32334683	1	14	from	modification	163:174	arg1	biopharmaceuticals					197:214	biopharmaceuticals	197:214	biopharmaceuticals	197:214	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	9	15	theme	large	1447:1451	arg1	differences					1453:1463	large differences	1447:1463	large differences such as the presence or absence of several monosaccharides	1447:1522	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	9	15	theme	large	1447:1451	arg1	absence					1489:1495	absence	1489:1495	absence	1489:1495	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	9	15	theme	large	1447:1451	arg1	presence					1477:1484	presence	1477:1484	presence	1477:1484	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	7	16	theme	other	1111:1115	arg1	glycoproteins					1124:1136	several other common glycoproteins	1103:1136	several other common glycoproteins	1103:1136	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	9	17	theme	monosaccharides	1508:1522	arg1	absence					1489:1495	absence	1489:1495	absence	1489:1495	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	9	17	theme	monosaccharides	1508:1522	arg1	presence					1477:1484	presence	1477:1484	presence	1477:1484	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	3	18	theme	analyses	531:538	arg1	robustness					513:522	the robustness	509:522	the robustness of the analyses	509:538	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	6	19	theme	potential	848:856	arg1	applications					858:869	three potential applications	842:869	three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control	842:1023	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	7	20	theme	glycoproteins	1189:1201	arg1	spectra					1178:1184	FTIR spectra	1173:1184	FTIR spectra of glycoproteins	1173:1201	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	9	21	theme	glycan	1565:1570	arg1	content					1591:1597	the glycan and monosaccharide content	1561:1597	content	1591:1597	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	3	22	theme	glycan	414:419	arg1	methods					430:436	current glycan analysis methods	406:436	current glycan analysis methods	406:436	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	0	23	theme	FTIR	0:3	arg1	spectroscopy					5:16	FTIR spectroscopy	0:16	FTIR spectroscopy as an analytical tool	0:38	FTIR spectroscopy as an analytical tool to compare glycosylation in therapeutic monoclonal antibodies.
32334683	7	24	theme	therapeutic	1035:1045	arg1	mAbs					1070:1073	mAbs	1070:1073	mAbs	1070:1073	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	7	24	theme	therapeutic	1035:1045	arg1	antibodies					1058:1067	Fourteen therapeutic monoclonal antibodies	1026:1067	Fourteen therapeutic monoclonal antibodies (mAbs)	1026:1074	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	8	25	theme	accurate	1354:1361	arg1	fingerprint					1363:1373	a global but accurate fingerprint	1341:1373	a global but accurate fingerprint of the glycosylation profile	1341:1402	We show that FTIR spectra of glycoproteins provide a global but accurate fingerprint of the glycosylation profile.
32334683	3	26	theme	analysis	421:428	arg1	methods					430:436	current glycan analysis methods	406:436	current glycan analysis methods	406:436	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	6	27	contain	has	838:840	arg2	applications					858:869	three potential applications	842:869	three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control	842:1023	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	6	27	contain	has	838:840	arg1	Use					699:701	Use	699:701	Use	699:701	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	7	28	theme	monoclonal	1047:1056	arg1	mAbs					1070:1073	mAbs	1070:1073	mAbs	1070:1073	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	7	28	theme	monoclonal	1047:1056	arg1	antibodies					1058:1067	Fourteen therapeutic monoclonal antibodies	1026:1067	Fourteen therapeutic monoclonal antibodies (mAbs)	1026:1074	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	6	29	theme	in-process	1006:1015	arg1	control					1017:1023	in-process control	1006:1023	in-process control	1006:1023	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	8	30	theme	profile	1396:1402	arg1	fingerprint					1363:1373	a global but accurate fingerprint	1341:1373	a global but accurate fingerprint of the glycosylation profile	1341:1402	We show that FTIR spectra of glycoproteins provide a global but accurate fingerprint of the glycosylation profile.
32334683	3	31	theme	lengthy	459:465	arg1	steps					486:490	multiple and lengthy sample preparation steps	446:490	multiple and lengthy sample preparation steps which can affect the robustness of the analyses	446:538	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	9	32	theme	content	1591:1597	arg1	modifications					1544:1556	smaller modifications	1536:1556	smaller modifications of the glycan and monosaccharide content	1536:1597	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	3	33	theme	sample	467:472	arg1	steps					486:490	multiple and lengthy sample preparation steps	446:490	multiple and lengthy sample preparation steps which can affect the robustness of the analyses	446:538	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	7	34	theme	common	1117:1122	arg1	glycoproteins					1124:1136	several other common glycoproteins	1103:1136	several other common glycoproteins	1103:1136	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	4	35	theme	orthogonal	560:569	arg1	method					590:595	orthogonal, direct and simple method	560:595	orthogonal, direct and simple method	560:595	The development of orthogonal, direct and simple method is therefore desirable.
32334683	3	36	theme	multiple	446:453	arg1	steps					486:490	multiple and lengthy sample preparation steps	446:490	multiple and lengthy sample preparation steps which can affect the robustness of the analyses	446:538	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	7	37	gly	glycoproteins	1124:1136	arg1	glycoproteins					1124:1136	several other common glycoproteins	1103:1136	several other common glycoproteins	1103:1136	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	2	38	dep	attribute	242:250	arg1	impacts					258:264	impacts	258:264	impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity)	258:398	It is a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity).
32334683	3	39	theme	current	406:412	arg1	methods					430:436	current glycan analysis methods	406:436	current glycan analysis methods	406:436	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	6	40	theme	original	921:928	arg1	innovator					931:939	innovator	931:939	innovator	931:939	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	6	40	theme	original	921:928	arg1	molecule					942:949	the original (innovator) molecule	917:949	the original (innovator) molecule	917:949	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	0	41	theme	analytical	24:33	arg1	tool					35:38	an analytical tool	21:38	an analytical tool	21:38	FTIR spectroscopy as an analytical tool to compare glycosylation in therapeutic monoclonal antibodies.
32334683	2	42	theme	quality	234:240	arg1	attribute					242:250	a critical quality attribute	223:250	a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity)	223:398	It is a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity).
32334683	2	42	theme	quality	234:240	arg1	It					217:218	It	217:218	It	217:218	It is a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity).
32334683	9	43	theme	monosaccharide	1576:1589	arg1	content					1591:1597	the glycan and monosaccharide content	1561:1597	content	1591:1597	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	7	44	theme	several	1103:1109	arg1	glycoproteins					1124:1136	several other common glycoproteins	1103:1136	several other common glycoproteins	1103:1136	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	5	45	theme	FTIR	654:657	arg1	spectroscopy					659:670	FTIR spectroscopy	654:670	FTIR spectroscopy	654:670	In this study, we suggest use of FTIR spectroscopy to address this challenge.
32334683	0	46	from	glycosylation	51:63	arg1	antibodies					91:100	therapeutic monoclonal antibodies	68:100	therapeutic monoclonal antibodies	68:100	FTIR spectroscopy as an analytical tool to compare glycosylation in therapeutic monoclonal antibodies.
32334683	2	47	theme	critical	225:232	arg1	attribute					242:250	a critical quality attribute	223:250	a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity)	223:398	It is a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity).
32334683	2	47	theme	critical	225:232	arg1	It					217:218	It	217:218	It	217:218	It is a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity).
32334683	6	48	theme	statistical	736:746	arg1	tools					748:752	statistical tools	736:752	statistical tools	736:752	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	7	49	theme	monosaccharide	1261:1274	arg1	compositions					1276:1287	their glycan and monosaccharide compositions	1244:1287	compositions	1276:1287	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	7	50	used	used	1148:1151	arg2	antibodies					1058:1067	Fourteen therapeutic monoclonal antibodies	1026:1067	Fourteen therapeutic monoclonal antibodies (mAbs)	1026:1074	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	7	50	used	used	1148:1151	arg2	protein					1091:1097	one Fc-fusion protein	1077:1097	one Fc-fusion protein	1077:1097	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	7	50	used	used	1148:1151	arg2	glycoproteins					1124:1136	several other common glycoproteins	1103:1136	several other common glycoproteins	1103:1136	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	7	50	used	used	1148:1151	arg2	mAbs					1070:1073	mAbs	1070:1073	mAbs	1070:1073	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	5	51	theme	spectroscopy	659:670	arg1	use					647:649	use	647:649	use of FTIR spectroscopy to address this challenge	647:696	In this study, we suggest use of FTIR spectroscopy to address this challenge.
32334683	6	52	theme	monosaccharide	814:827	arg1	profile					829:835	monosaccharide profile	814:835	monosaccharide profile	814:835	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	6	53	theme	biosimilar	902:911	arg1	glycosylation					883:895	glycosylation	883:895	glycosylation of a biosimilar	883:911	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	6	53	theme	biosimilar	902:911	arg1	innovator					931:939	innovator	931:939	innovator	931:939	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	6	53	theme	biosimilar	902:911	arg1	molecule					942:949	the original (innovator) molecule	917:949	the original (innovator) molecule	917:949	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	2	54	theme	product	266:272	arg1	solubility					274:283	product solubility	266:283	product solubility	266:283	It is a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity).
32334683	8	55	theme	glycosylation	1382:1394	arg1	profile					1396:1402	the glycosylation profile	1378:1402	the glycosylation profile	1378:1402	We show that FTIR spectra of glycoproteins provide a global but accurate fingerprint of the glycosylation profile.
32334683	1	56	theme	common	129:134	arg1	modification					163:174	the most common protein post-translational modification	120:174	the most common protein post-translational modification (PTM)	120:180	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	1	56	theme	common	129:134	arg1	Glycosylation					103:115	Glycosylation	103:115	Glycosylation	103:115	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	1	56	theme	common	129:134	arg1	PTM					177:179	PTM	177:179	PTM	177:179	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	7	57	gly	glycoproteins	1189:1201	arg1	glycoproteins					1189:1201	glycoproteins	1189:1201	glycoproteins	1189:1201	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	8	58	theme	global	1343:1348	arg1	fingerprint					1363:1373	a global but accurate fingerprint	1341:1373	a global but accurate fingerprint of the glycosylation profile	1341:1402	We show that FTIR spectra of glycoproteins provide a global but accurate fingerprint of the glycosylation profile.
32334683	6	59	theme	glycosylation	797:809	arg1	terms					788:792	terms	788:792	terms of glycosylation or monosaccharide profile	788:835	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	9	60	theme	smaller	1536:1542	arg1	modifications					1544:1556	smaller modifications	1536:1556	smaller modifications of the glycan and monosaccharide content	1536:1597	This fingerprint is not only sensitive to large differences such as the presence or absence of several monosaccharides but also to smaller modifications of the glycan and monosaccharide content.
32334683	1	61	theme	protein	136:142	arg1	modification					163:174	the most common protein post-translational modification	120:174	the most common protein post-translational modification (PTM)	120:180	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	1	61	theme	protein	136:142	arg1	Glycosylation					103:115	Glycosylation	103:115	Glycosylation	103:115	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	1	61	theme	protein	136:142	arg1	PTM					177:179	PTM	177:179	PTM	177:179	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	3	62	theme	preparation	474:484	arg1	steps					486:490	multiple and lengthy sample preparation steps	446:490	multiple and lengthy sample preparation steps which can affect the robustness of the analyses	446:538	Yet, current glycan analysis methods involve multiple and lengthy sample preparation steps which can affect the robustness of the analyses.
32334683	6	63	theme	technique	711:719	arg1	Use					699:701	Use	699:701	Use	699:701	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	1	64	theme	post-translational	144:161	arg1	modification					163:174	the most common protein post-translational modification	120:174	the most common protein post-translational modification (PTM)	120:180	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	1	64	theme	post-translational	144:161	arg1	Glycosylation					103:115	Glycosylation	103:115	Glycosylation	103:115	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	1	64	theme	post-translational	144:161	arg1	PTM					177:179	PTM	177:179	PTM	177:179	Glycosylation is the most common protein post-translational modification (PTM), especially in biopharmaceuticals.
32334683	6	65	theme	consistency	985:995	arg1	monitoring					956:965	monitoring	956:965	monitoring of batch-to-batch consistency	956:995	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
32334683	7	66	theme	spectral	1211:1218	arg1	variations					1220:1229	spectral variations	1211:1229	spectral variations according to their glycan and monosaccharide compositions	1211:1287	Fourteen therapeutic monoclonal antibodies (mAbs), one Fc-fusion protein and several other common glycoproteins have been used to demonstrate that FTIR spectra of glycoproteins display spectral variations according to their glycan and monosaccharide compositions.
32334683	2	67	dep	immunogenicity	384:397	arg1	e.g.					379:382	e.g.	379:382	e.g.	379:382	It is a critical quality attribute as it impacts product solubility, stability, half-life, pharmacokinetics and pharmacodynamics (PK/PD), bioactivity and safety (e.g. immunogenicity).
32334683	8	68	theme	FTIR	1303:1306	arg1	spectra					1308:1314	FTIR spectra	1303:1314	FTIR spectra of glycoproteins	1303:1331	We show that FTIR spectra of glycoproteins provide a global but accurate fingerprint of the glycosylation profile.
32334683	6	69	theme	batch-to-batch	970:983	arg1	consistency					985:995	batch-to-batch consistency	970:995	batch-to-batch consistency	970:995	Use of this technique, combined with statistical tools, to compare samples or batches in terms of glycosylation or monosaccharide profile, has three potential applications: to compare glycosylation of a biosimilar and the original (innovator) molecule, for monitoring of batch-to-batch consistency, and for in-process control.
33556394	3	0	contain	carries	442:448	arg1	N-terminus					431:440	the β1AR N-terminus	422:440	the β1AR N-terminus	422:440	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	3	0	contain	carries	442:448	arg2	modifications					459:471	O-glycan modifications	450:471	O-glycan modifications at Ser37/Ser41	450:486	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	6	1	theme	O-glycan	1227:1234	arg1	modification					1236:1247	this O-glycan modification	1222:1247	this O-glycan modification	1222:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	9	2	theme	cleavage	1779:1786	arg1	mutant					1803:1808	a cleavage resistant β1AR mutant	1777:1808	a cleavage resistant β1AR mutant	1777:1808	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	3	3	theme	downstream	605:614	arg1	effectors					616:624	downstream effectors	605:624	downstream effectors	605:624	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	9	4	theme	β1AR	1798:1801	arg1	mutant					1803:1808	a cleavage resistant β1AR mutant	1777:1808	a cleavage resistant β1AR mutant	1777:1808	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	1	5	theme	catecholamine	208:220	arg1	action					222:227	catecholamine action	208:227	catecholamine action in cardiomyocytes	208:245	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	6	6	theme	major	1007:1011	arg1	site					1029:1032	the major O-glycosylation site	1003:1032	the major O-glycosylation site on the β1AR N-terminus	1003:1055	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	6	theme	major	1007:1011	arg1	Ser41					994:998	Ser41	994:998	Ser41	994:998	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	7	theme	N-terminal	1185:1194	arg1	S41↓L42					1167:1173	S41↓L42	1167:1173	S41↓L42	1167:1173	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	7	theme	N-terminal	1185:1194	arg1	site					1205:1208	a second N-terminal cleavage site	1176:1208	a second N-terminal cleavage site adjacent to this O-glycan modification	1176:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	2	8	theme	post-translational	324:341	arg1	modifications					343:355	post-translational modifications	324:355	post-translational modifications that impact on signaling responses	324:390	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	1	9	from	cardiomyocytes	232:245	arg1	receptors					159:167	β1-adrenergic receptors	145:167	β1-adrenergic receptors (β1ARs)	145:175	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	1	9	from	cardiomyocytes	232:245	arg1	mediators					195:203	the principle mediators	181:203	the principle mediators of catecholamine action in cardiomyocytes	181:245	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	6	10	theme	β1-AR	1268:1272	arg1	cleavage					1285:1292	β1-AR N-terminal cleavage	1268:1292	β1-AR N-terminal cleavage at R31↓L32	1268:1303	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	10	11	theme	responses	1934:1942	arg1	determinant					1914:1924	a structural determinant	1901:1924	a structural determinant of β1AR responses that can be targeted for therapeutic advantage	1901:1989	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	10	11	theme	responses	1934:1942	arg1	N-terminus					1887:1896	the β1AR N-terminus	1878:1896	the β1AR N-terminus	1878:1896	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	1	12	from	action	222:227	arg1	cardiomyocytes					232:245	cardiomyocytes	232:245	cardiomyocytes	232:245	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	1	13	theme	β1-adrenergic	145:157	arg1	receptors					159:167	β1-adrenergic receptors	145:167	β1-adrenergic receptors (β1ARs)	145:175	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	1	13	theme	β1-adrenergic	145:157	arg1	mediators					195:203	the principle mediators	181:203	the principle mediators of catecholamine action in cardiomyocytes	181:245	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	1	13	theme	β1-adrenergic	145:157	arg1	β1ARs					170:174	β1ARs	170:174	β1ARs	170:174	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	8	14	theme	N-terminal	1536:1545	arg1	truncation					1547:1556	N-terminal truncation	1536:1556	N-terminal truncation at R31↓L32 by ADAM17	1536:1577	This study shows that redox-inactivation of cardiomyocyte β1ARs is via a mechanism involving N-terminal truncation at R31↓L32 by ADAM17.
33556394	7	15	theme	catecholamine	1395:1407	arg1	responsiveness					1409:1422	catecholamine responsiveness	1395:1422	catecholamine responsiveness	1395:1422	We previously reported that oxidative stress leads to a decrease in β1AR expression and catecholamine responsiveness in cardiomyocytes.
33556394	2	16	dep	impact	362:367	arg1	modifications					343:355	post-translational modifications	324:355	post-translational modifications that impact on signaling responses	324:390	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	2	17	theme	extracellular	283:295	arg1	target					313:318	a target	311:318	a target for post-translational modifications that impact on signaling responses	311:390	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	2	17	theme	extracellular	283:295	arg1	N-terminus					297:306	the β1AR extracellular N-terminus	274:306	the β1AR extracellular N-terminus	274:306	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	5	18	theme	β1AR	880:883	arg1	result					908:913	a result	906:913	a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	906:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	18	theme	β1AR	880:883	arg1	species					885:891	the truncated β1AR species	866:891	the truncated β1AR species	866:891	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	19	theme	regulated	930:938	arg1	cleavage					951:958	an O-glycan regulated N-terminal cleavage	918:958	an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	918:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	0	20	theme	redox-dependent	72:86	arg1	downregulation					88:101	redox-dependent downregulation	72:101	redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors	72:142	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	5	21	theme	cleavage	951:958	arg1	result					908:913	a result	906:913	a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	906:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	21	theme	cleavage	951:958	arg1	species					885:891	the truncated β1AR species	866:891	the truncated β1AR species	866:891	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	2	22	from	impact	362:367	arg1	responses					382:390	signaling responses	372:390	signaling responses	372:390	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	10	23	theme	therapeutic	1969:1979	arg1	advantage					1981:1989	therapeutic advantage	1969:1989	therapeutic advantage	1969:1989	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	5	24	theme	other	784:788	arg1	types					796:800	other cells types	784:800	other cells types	784:800	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	7	25	from	expression	1380:1389	arg1	cardiomyocytes					1427:1440	cardiomyocytes	1427:1440	cardiomyocytes	1427:1440	We previously reported that oxidative stress leads to a decrease in β1AR expression and catecholamine responsiveness in cardiomyocytes.
33556394	0	26	theme	β1-adrenergic	120:132	arg1	receptors					134:142	cardiomyocyte β1-adrenergic receptors	106:142	cardiomyocyte β1-adrenergic receptors	106:142	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	9	27	theme	truncated	1639:1647	arg1	β1ARs					1649:1653	N-terminally truncated β1ARs	1626:1653	N-terminally truncated β1ARs	1626:1653	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	7	28	theme	β1AR	1375:1378	arg1	expression					1380:1389	β1AR expression	1375:1389	β1AR expression	1375:1389	We previously reported that oxidative stress leads to a decrease in β1AR expression and catecholamine responsiveness in cardiomyocytes.
33556394	3	29	theme	β1AR	426:429	arg1	N-terminus					431:440	the β1AR N-terminus	422:440	the β1AR N-terminus	422:440	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	0	30	theme	β1-adrenergic	0:12	arg1	cleavage					34:41	β1-adrenergic receptor N-terminal cleavage	0:41	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.	0:143	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	3	31	theme	N-terminal	524:533	arg1	cleavage					535:542	β1AR N-terminal cleavage	519:542	β1AR N-terminal cleavage	519:542	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	0	32	theme	N-terminal	23:32	arg1	cleavage					34:41	β1-adrenergic receptor N-terminal cleavage	0:41	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.	0:143	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	6	33	theme	O-glycan	1074:1081	arg1	modification					1083:1094	an O-glycan modification	1071:1094	an O-glycan modification at Ser41	1071:1103	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	5	34	theme	truncated	839:847	arg1	species					849:855	both full-length and N-terminally truncated species	805:855	both full-length and N-terminally truncated species	805:855	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	34	theme	truncated	839:847	arg1	β1ARs					742:746	β1ARs	742:746	β1ARs	742:746	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	8	35	theme	cardiomyocyte	1487:1499	arg1	β1ARs					1501:1505	cardiomyocyte β1ARs	1487:1505	cardiomyocyte β1ARs	1487:1505	This study shows that redox-inactivation of cardiomyocyte β1ARs is via a mechanism involving N-terminal truncation at R31↓L32 by ADAM17.
33556394	2	36	theme	signaling	372:380	arg1	responses					382:390	signaling responses	372:390	signaling responses	372:390	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	10	37	theme	β1AR	1882:1885	arg1	determinant					1914:1924	a structural determinant	1901:1924	a structural determinant of β1AR responses that can be targeted for therapeutic advantage	1901:1989	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	10	37	theme	β1AR	1882:1885	arg1	N-terminus					1887:1896	the β1AR N-terminus	1878:1896	the β1AR N-terminus	1878:1896	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	3	38	theme	β1AR	587:590	arg1	signaling					592:600	β1AR signaling	587:600	β1AR signaling to downstream effectors	587:624	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	6	39	theme	β1-AR	1147:1151	arg1	N-terminus					1153:1162	the β1-AR N-terminus	1143:1162	the β1-AR N-terminus	1143:1162	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	4	40	theme	β1AR	666:669	arg1	cleavage					682:689	β1AR N-terminal cleavage	666:689	β1AR N-terminal cleavage in cells	666:698	However, the site(s) and mechanism for β1AR N-terminal cleavage in cells was not identified.
33556394	6	41	from	R31↓L32	1297:1303	arg1	cleavage					1285:1292	β1-AR N-terminal cleavage	1268:1292	β1-AR N-terminal cleavage at R31↓L32	1268:1303	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	42	from	Ser41	1099:1103	arg1	modification					1083:1094	an O-glycan modification	1071:1094	an O-glycan modification at Ser41	1071:1103	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	5	43	from	result	908:913	arg1	R31↓L32					973:979	R31↓L32	973:979	R31↓L32	973:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	1	44	theme	principle	185:193	arg1	receptors					159:167	β1-adrenergic receptors	145:167	β1-adrenergic receptors (β1ARs)	145:175	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	1	44	theme	principle	185:193	arg1	mediators					195:203	the principle mediators	181:203	the principle mediators of catecholamine action in cardiomyocytes	181:245	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	9	45	theme	resistant	1788:1796	arg1	mutant					1803:1808	a cleavage resistant β1AR mutant	1777:1808	a cleavage resistant β1AR mutant	1777:1808	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	6	46	theme	adjacent	1210:1217	arg1	S41↓L42					1167:1173	S41↓L42	1167:1173	S41↓L42	1167:1173	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	46	theme	adjacent	1210:1217	arg1	site					1205:1208	a second N-terminal cleavage site	1176:1208	a second N-terminal cleavage site adjacent to this O-glycan modification	1176:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	47	gly	O-glycosylation	1013:1027	arg2	site					1029:1032	the major O-glycosylation site	1003:1032	the major O-glycosylation site on the β1AR N-terminus	1003:1055	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	47	gly	O-glycosylation	1013:1027	arg2	Ser41					994:998	Ser41	994:998	Ser41	994:998	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	10	48	theme	β1AR	1929:1932	arg1	responses					1934:1942	β1AR responses	1929:1942	β1AR responses that can be targeted for therapeutic advantage	1929:1989	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	6	49	theme	O-glycosylation	1013:1027	arg1	site					1029:1032	the major O-glycosylation site	1003:1032	the major O-glycosylation site on the β1AR N-terminus	1003:1055	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	49	theme	O-glycosylation	1013:1027	arg1	Ser41					994:998	Ser41	994:998	Ser41	994:998	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	9	50	theme	mutant	1803:1808	arg1	overexpression					1759:1772	overexpression	1759:1772	overexpression of a cleavage resistant β1AR mutant	1759:1808	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	6	51	theme	cleavage	1196:1203	arg1	S41↓L42					1167:1173	S41↓L42	1167:1173	S41↓L42	1167:1173	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	51	theme	cleavage	1196:1203	arg1	site					1205:1208	a second N-terminal cleavage site	1176:1208	a second N-terminal cleavage site adjacent to this O-glycan modification	1176:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	1	52	theme	action	222:227	arg1	receptors					159:167	β1-adrenergic receptors	145:167	β1-adrenergic receptors (β1ARs)	145:175	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	1	52	theme	action	222:227	arg1	mediators					195:203	the principle mediators	181:203	the principle mediators of catecholamine action in cardiomyocytes	181:245	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	9	53	theme	doxorubicin-dependent	1822:1842	arg1	apoptosis					1844:1852	doxorubicin-dependent apoptosis	1822:1852	doxorubicin-dependent apoptosis	1822:1852	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	9	54	theme	previous	1600:1607	arg1	observation					1609:1619	the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis	1596:1756	the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis	1596:1756	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	4	55	from	cleavage	682:689	arg1	cells					694:698	cells	694:698	cells	694:698	However, the site(s) and mechanism for β1AR N-terminal cleavage in cells was not identified.
33556394	6	56	theme	N-terminal	1274:1283	arg1	cleavage					1285:1292	β1-AR N-terminal cleavage	1268:1292	β1-AR N-terminal cleavage at R31↓L32	1268:1303	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	8	57	from	R31↓L32	1561:1567	arg1	truncation					1547:1556	N-terminal truncation	1536:1556	N-terminal truncation at R31↓L32 by ADAM17	1536:1577	This study shows that redox-inactivation of cardiomyocyte β1ARs is via a mechanism involving N-terminal truncation at R31↓L32 by ADAM17.
33556394	10	58	theme	structural	1903:1912	arg1	determinant					1914:1924	a structural determinant	1901:1924	a structural determinant of β1AR responses that can be targeted for therapeutic advantage	1901:1989	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	10	58	theme	structural	1903:1912	arg1	N-terminus					1887:1896	the β1AR N-terminus	1878:1896	the β1AR N-terminus	1878:1896	These studies identify the β1AR N-terminus as a structural determinant of β1AR responses that can be targeted for therapeutic advantage.
33556394	2	59	theme	β1AR	278:281	arg1	target					313:318	a target	311:318	a target for post-translational modifications that impact on signaling responses	311:390	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	2	59	theme	β1AR	278:281	arg1	N-terminus					297:306	the β1AR extracellular N-terminus	274:306	the β1AR extracellular N-terminus	274:306	We previously showed that the β1AR extracellular N-terminus is a target for post-translational modifications that impact on signaling responses.
33556394	5	60	theme	O-glycan	921:928	arg1	cleavage					951:958	an O-glycan regulated N-terminal cleavage	918:958	an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	918:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	61	theme	full-length	810:820	arg1	species					849:855	both full-length and N-terminally truncated species	805:855	both full-length and N-terminally truncated species	805:855	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	61	theme	full-length	810:820	arg1	β1ARs					742:746	β1ARs	742:746	β1ARs	742:746	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	1	62	from	mediators	195:203	arg1	cardiomyocytes					232:245	cardiomyocytes	232:245	cardiomyocytes	232:245	β1-adrenergic receptors (β1ARs) are the principle mediators of catecholamine action in cardiomyocytes.
33556394	5	63	theme	N-terminal	940:949	arg1	cleavage					951:958	an O-glycan regulated N-terminal cleavage	918:958	an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	918:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	6	64	theme	β1AR	1041:1044	arg1	N-terminus					1046:1055	the β1AR N-terminus	1037:1055	the β1AR N-terminus	1037:1055	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	0	65	theme	cardiomyocyte	106:118	arg1	receptors					134:142	cardiomyocyte β1-adrenergic receptors	106:142	cardiomyocyte β1-adrenergic receptors	106:142	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	6	66	theme	second	1178:1183	arg1	S41↓L42					1167:1173	S41↓L42	1167:1173	S41↓L42	1167:1173	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	66	theme	second	1178:1183	arg1	site					1205:1208	a second N-terminal cleavage site	1176:1208	a second N-terminal cleavage site adjacent to this O-glycan modification	1176:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	0	67	theme	receptors	134:142	arg1	downregulation					88:101	redox-dependent downregulation	72:101	redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors	72:142	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	6	68	from	site	1029:1032	arg1	N-terminus					1046:1055	the β1AR N-terminus	1037:1055	the β1AR N-terminus	1037:1055	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	5	69	theme	cells	790:794	arg1	types					796:800	other cells types	784:800	other cells types	784:800	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	0	70	theme	receptor	14:21	arg1	cleavage					34:41	β1-adrenergic receptor N-terminal cleavage	0:41	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.	0:143	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	5	71	from	R31↓L32	973:979	arg1	result					908:913	a result	906:913	a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	906:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	71	from	R31↓L32	973:979	arg1	species					885:891	the truncated β1AR species	866:891	the truncated β1AR species	866:891	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	71	from	R31↓L32	973:979	arg1	cleavage					951:958	an O-glycan regulated N-terminal cleavage	918:958	an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	918:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	7	72	from	responsiveness	1409:1422	arg1	cardiomyocytes					1427:1440	cardiomyocytes	1427:1440	cardiomyocytes	1427:1440	We previously reported that oxidative stress leads to a decrease in β1AR expression and catecholamine responsiveness in cardiomyocytes.
33556394	5	73	theme	truncated	870:878	arg1	result					908:913	a result	906:913	a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32	906:979	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	5	73	theme	truncated	870:878	arg1	species					885:891	the truncated β1AR species	866:891	the truncated β1AR species	866:891	This study shows that β1ARs are expressed in cardiomyocytes and other cells types as both full-length and N-terminally truncated species and that the truncated β1AR species is formed as a result of an O-glycan regulated N-terminal cleavage by ADAM17 at R31↓L32.
33556394	4	74	theme	site	640:643	arg1	s					645:645	the site(s)	636:646	the site(s)	636:646	However, the site(s) and mechanism for β1AR N-terminal cleavage in cells was not identified.
33556394	9	75	theme	AKT	1682:1684	arg1	pathway					1686:1692	an AKT pathway	1679:1692	an AKT pathway that affords protection against doxorubicin-dependent apoptosis	1679:1756	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	7	76	theme	oxidative	1335:1343	arg1	stress					1345:1350	oxidative stress	1335:1350	oxidative stress	1335:1350	We previously reported that oxidative stress leads to a decrease in β1AR expression and catecholamine responsiveness in cardiomyocytes.
33556394	6	77	from	S41↓L42	1167:1173	arg1	cleavage					1131:1138	ADAM17-dependent cleavage	1114:1138	ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification	1114:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	3	78	theme	β1AR	519:522	arg1	cleavage					535:542	β1AR N-terminal cleavage	519:542	β1AR N-terminal cleavage	519:542	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	3	79	theme	O-glycan	450:457	arg1	modifications					459:471	O-glycan modifications	450:471	O-glycan modifications at Ser37/Ser41	450:486	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	3	80	theme	N-terminal	554:563	arg1	truncation					565:574	N-terminal truncation	554:574	N-terminal truncation	554:574	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	0	81	dep	cleavage	34:41	arg1	mechanism					58:66	the mechanism	54:66	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.	0:143	β1-adrenergic receptor N-terminal cleavage by ADAM17; the mechanism for redox-dependent downregulation of cardiomyocyte β1-adrenergic receptors.
33556394	3	82	from	Ser37/Ser41	476:486	arg1	modifications					459:471	O-glycan modifications	450:471	O-glycan modifications at Ser37/Ser41	450:486	Specifically, we showed that the β1AR N-terminus carries O-glycan modifications at Ser37/Ser41, that O-glycosylation prevents β1AR N-terminal cleavage, and that N-terminal truncation influences β1AR signaling to downstream effectors.
33556394	9	83	theme	doxorubicin-dependent	1726:1746	arg1	apoptosis					1748:1756	doxorubicin-dependent apoptosis	1726:1756	doxorubicin-dependent apoptosis	1726:1756	In keeping with the previous observation that N-terminally truncated β1ARs constitutively activate an AKT pathway that affords protection against doxorubicin-dependent apoptosis, overexpression of a cleavage resistant β1AR mutant exacerbates doxorubicin-dependent apoptosis.
33556394	7	84	from	decrease	1363:1370	arg1	expression					1380:1389	β1AR expression	1375:1389	β1AR expression	1375:1389	We previously reported that oxidative stress leads to a decrease in β1AR expression and catecholamine responsiveness in cardiomyocytes.
33556394	7	84	from	decrease	1363:1370	arg1	responsiveness					1409:1422	catecholamine responsiveness	1395:1422	catecholamine responsiveness	1395:1422	We previously reported that oxidative stress leads to a decrease in β1AR expression and catecholamine responsiveness in cardiomyocytes.
33556394	6	85	theme	N-terminus	1153:1162	arg1	cleavage					1131:1138	ADAM17-dependent cleavage	1114:1138	ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification	1114:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	6	86	theme	ADAM17-dependent	1114:1129	arg1	cleavage					1131:1138	ADAM17-dependent cleavage	1114:1138	ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification	1114:1247	We identify Ser41 as the major O-glycosylation site on the β1AR N-terminus and show that an O-glycan modification at Ser41 prevents ADAM17-dependent cleavage of the β1-AR N-terminus at S41↓L42, a second N-terminal cleavage site adjacent to this O-glycan modification (and it attenuates β1-AR N-terminal cleavage at R31↓L32).
33556394	4	87	theme	N-terminal	671:680	arg1	cleavage					682:689	β1AR N-terminal cleavage	666:689	β1AR N-terminal cleavage in cells	666:698	However, the site(s) and mechanism for β1AR N-terminal cleavage in cells was not identified.
33556394	8	88	theme	β1ARs	1501:1505	arg1	redox-inactivation					1465:1482	redox-inactivation	1465:1482	redox-inactivation of cardiomyocyte β1ARs	1465:1505	This study shows that redox-inactivation of cardiomyocyte β1ARs is via a mechanism involving N-terminal truncation at R31↓L32 by ADAM17.
32338884	5	0	theme	material	817:824	arg1	applications					834:845	future material science applications	810:845	future material science applications of carbohydrates	810:862	Quick access to polysaccharides provides the basis for future material science applications of carbohydrates.
32338884	1	1	theme	modulatory	158:167	arg1	functions					169:177	various structural and modulatory functions	135:177	various structural and modulatory functions	135:177	Polysaccharides are the most abundant biopolymers on earth that serve various structural and modulatory functions.
32338884	2	2	dep	Pure	180:183	arg1	defined					197:203	defined	197:203	defined	197:203	Pure, completely defined linear and branched polysaccharides are essential to understand carbohydrate structure and function.
32338884	3	3	theme	heroic	370:375	arg1	efforts					377:383	heroic efforts	370:383	heroic efforts	370:383	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	4	4	theme	151-mer	732:738	arg1	polymannoside					740:752	a multiple-branched 151-mer polymannoside	712:752	a multiple-branched 151-mer polymannoside	712:752	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	4	5	dep	h.	613:614	arg1	yielded					704:710	yielded	704:710	yielded a multiple-branched 151-mer polymannoside	704:752	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	3	6	theme	chemical	411:418	arg1	syntheses					437:445	chemical and/or enzymatic syntheses	411:445	chemical and/or enzymatic syntheses of polysaccharides	411:464	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	3	6	theme	chemical	411:418	arg1	92-mers					474:480	long 92-mers	469:480	long 92-mers	469:480	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	4	7	theme	block	627:631	arg1	coupling					633:640	Convergent block coupling	616:640	Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA,	616:702	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	0	8	theme	Automated	38:46	arg1	Assembly					55:62	Automated Glycan Assembly	38:62	Automated Glycan Assembly	38:62	Total Synthesis of Polysaccharides by Automated Glycan Assembly.
32338884	4	9	theme	Convergent	616:625	arg1	coupling					633:640	Convergent block coupling	616:640	Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA,	616:702	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	5	10	theme	science	826:832	arg1	applications					834:845	future material science applications	810:845	future material science applications of carbohydrates	810:862	Quick access to polysaccharides provides the basis for future material science applications of carbohydrates.
32338884	0	11	theme	Total	0:4	arg1	Synthesis					6:14	Total Synthesis	0:14	Total Synthesis of Polysaccharides by Automated Glycan Assembly	0:62	Total Synthesis of Polysaccharides by Automated Glycan Assembly.
32338884	1	12	theme	abundant	94:101	arg1	biopolymers					103:113	the most abundant biopolymers	85:113	the most abundant biopolymers on earth that serve various structural and modulatory functions	85:177	Polysaccharides are the most abundant biopolymers on earth that serve various structural and modulatory functions.
32338884	1	12	theme	abundant	94:101	arg1	Polysaccharides					65:79	Polysaccharides	65:79	Polysaccharides	65:79	Polysaccharides are the most abundant biopolymers on earth that serve various structural and modulatory functions.
32338884	0	13	theme	Polysaccharides	19:33	arg1	Synthesis					6:14	Total Synthesis	0:14	Total Synthesis of Polysaccharides by Automated Glycan Assembly	0:62	Total Synthesis of Polysaccharides by Automated Glycan Assembly.
32338884	4	14	theme	201-step	583:590	arg1	synthesis					592:600	a 201-step synthesis	581:600	a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside	581:752	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	3	15	theme	Polysaccharide	306:319	arg1	isolation					321:329	Polysaccharide isolation	306:329	Polysaccharide isolation	306:329	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	4	16	theme	fragments	676:684	arg1	coupling					633:640	Convergent block coupling	616:640	Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA,	616:702	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	3	17	theme	enzymatic	427:435	arg1	syntheses					437:445	chemical and/or enzymatic syntheses	411:445	chemical and/or enzymatic syntheses of polysaccharides	411:464	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	3	17	theme	enzymatic	427:435	arg1	92-mers					474:480	long 92-mers	469:480	long 92-mers	469:480	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	5	18	theme	Quick	755:759	arg1	access					761:766	Quick access	755:766	Quick access to polysaccharides	755:785	Quick access to polysaccharides provides the basis for future material science applications of carbohydrates.
32338884	4	19	theme	oligosaccharide	660:674	arg1	fragments					676:684	30- and 31-mer oligosaccharide fragments	645:684	30- and 31-mer oligosaccharide fragments	645:684	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	3	20	theme	long	469:472	arg1	syntheses					437:445	chemical and/or enzymatic syntheses	411:445	chemical and/or enzymatic syntheses of polysaccharides	411:464	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	3	20	theme	long	469:472	arg1	92-mers					474:480	long 92-mers	469:480	long 92-mers	469:480	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	4	21	theme	multiple-branched	714:730	arg1	polymannoside					740:752	a multiple-branched 151-mer polymannoside	712:752	a multiple-branched 151-mer polymannoside	712:752	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	4	22	theme	glycan	512:517	arg1	AGA					529:531	AGA	529:531	AGA	529:531	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	4	22	theme	glycan	512:517	arg1	assembly					519:526	automated glycan assembly	502:526	automated glycan assembly (AGA)	502:532	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	3	23	theme	polysaccharides	450:464	arg1	syntheses					437:445	chemical and/or enzymatic syntheses	411:445	chemical and/or enzymatic syntheses of polysaccharides	411:464	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	3	23	theme	polysaccharides	450:464	arg1	92-mers					474:480	long 92-mers	469:480	long 92-mers	469:480	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	4	24	theme	100-mer	554:560	arg1	polysaccharide					562:575	a 100-mer polysaccharide	552:575	a 100-mer polysaccharide	552:575	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	4	25	theme	automated	502:510	arg1	AGA					529:531	AGA	529:531	AGA	529:531	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	4	25	theme	automated	502:510	arg1	assembly					519:526	automated glycan assembly	502:526	automated glycan assembly (AGA)	502:532	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	0	26	theme	Glycan	48:53	arg1	Assembly					55:62	Automated Glycan Assembly	38:62	Automated Glycan Assembly	38:62	Total Synthesis of Polysaccharides by Automated Glycan Assembly.
32338884	2	27	theme	branched	216:223	arg1	polysaccharides					225:239	Pure, completely defined linear and branched polysaccharides	180:239	Pure, completely defined linear and branched polysaccharides	180:239	Pure, completely defined linear and branched polysaccharides are essential to understand carbohydrate structure and function.
32338884	2	28	theme	Pure	180:183	arg1	polysaccharides					225:239	Pure, completely defined linear and branched polysaccharides	180:239	Pure, completely defined linear and branched polysaccharides	180:239	Pure, completely defined linear and branched polysaccharides are essential to understand carbohydrate structure and function.
32338884	1	29	from	biopolymers	103:113	arg1	earth					118:122	earth	118:122	earth that serve various structural and modulatory functions	118:177	Polysaccharides are the most abundant biopolymers on earth that serve various structural and modulatory functions.
32338884	5	30	theme	future	810:815	arg1	applications					834:845	future material science applications	810:845	future material science applications of carbohydrates	810:862	Quick access to polysaccharides provides the basis for future material science applications of carbohydrates.
32338884	4	31	theme	30-	645:647	arg1	fragments					676:684	30- and 31-mer oligosaccharide fragments	645:684	30- and 31-mer oligosaccharide fragments	645:684	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	3	32	theme	heterogeneous	340:352	arg1	mixtures					354:361	heterogeneous mixtures	340:361	heterogeneous mixtures	340:361	Polysaccharide isolation provides heterogeneous mixtures, while heroic efforts were required to complete chemical and/or enzymatic syntheses of polysaccharides as long 92-mers.
32338884	2	33	theme	linear	205:210	arg1	polysaccharides					225:239	Pure, completely defined linear and branched polysaccharides	180:239	Pure, completely defined linear and branched polysaccharides	180:239	Pure, completely defined linear and branched polysaccharides are essential to understand carbohydrate structure and function.
32338884	1	34	theme	various	135:141	arg1	functions					169:177	various structural and modulatory functions	135:177	various structural and modulatory functions	135:177	Polysaccharides are the most abundant biopolymers on earth that serve various structural and modulatory functions.
32338884	2	35	theme	carbohydrate	269:280	arg1	structure					282:290	carbohydrate structure	269:290	carbohydrate structure	269:290	Pure, completely defined linear and branched polysaccharides are essential to understand carbohydrate structure and function.
32338884	1	36	theme	structural	143:152	arg1	functions					169:177	various structural and modulatory functions	135:177	various structural and modulatory functions	135:177	Polysaccharides are the most abundant biopolymers on earth that serve various structural and modulatory functions.
32338884	4	37	theme	31-mer	653:658	arg1	fragments					676:684	30- and 31-mer oligosaccharide fragments	645:684	30- and 31-mer oligosaccharide fragments	645:684	Here, we show that automated glycan assembly (AGA) enables access to a 100-mer polysaccharide via a 201-step synthesis within 188 h. Convergent block coupling of 30- and 31-mer oligosaccharide fragments, prepared by AGA, yielded a multiple-branched 151-mer polymannoside.
32338884	5	38	theme	carbohydrates	850:862	arg1	applications					834:845	future material science applications	810:845	future material science applications of carbohydrates	810:862	Quick access to polysaccharides provides the basis for future material science applications of carbohydrates.
32579622	2	0	theme	glycan	402:407	arg1	GBPs					427:430	GBPs	427:430	GBPs	427:430	These glycans were printed as a microarray to investigate their interactions with a panel of glycan binding proteins (GBPs).
32579622	2	0	theme	glycan	402:407	arg1	proteins					417:424	glycan binding proteins	402:424	glycan binding proteins (GBPs)	402:431	These glycans were printed as a microarray to investigate their interactions with a panel of glycan binding proteins (GBPs).
32579622	1	1	theme	poly-LacNAc	200:210	arg1	glycans					213:219	poly-N-acetyllactosamine (poly-LacNAc) glycans	174:219	poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	174:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	3	2	theme	Binding	434:440	arg1	affinities					442:451	Binding affinities	434:451	Binding affinities	434:451	Binding affinities revealed that the avidity of GBPs could be largely affected by the length and the patterns of sialylation and fucosylation.
32579622	1	3	theme	facile	92:97	arg1	strategy					126:133	A facile enzymatic modular assembly strategy	90:133	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	90:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	1	4	theme	glycans	213:219	arg1	synthesis					161:169	the preparative-scale synthesis	139:169	the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	139:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	0	5	theme	modular	10:16	arg1	synthesis					18:26	Enzymatic modular synthesis and microarray assay	0:47	synthesis	18:26	Enzymatic modular synthesis and microarray assay of poly-N-acetyllactosamine derivatives.
32579622	3	6	theme	sialylation	547:557	arg1	length					520:525	the length	516:525	the length	516:525	Binding affinities revealed that the avidity of GBPs could be largely affected by the length and the patterns of sialylation and fucosylation.
32579622	3	6	theme	sialylation	547:557	arg1	patterns					535:542	the patterns	531:542	the patterns of sialylation and fucosylation	531:574	Binding affinities revealed that the avidity of GBPs could be largely affected by the length and the patterns of sialylation and fucosylation.
32579622	1	7	theme	enzymatic	99:107	arg1	strategy					126:133	A facile enzymatic modular assembly strategy	90:133	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	90:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	0	8	theme	Enzymatic	0:8	arg1	synthesis					18:26	Enzymatic modular synthesis and microarray assay	0:47	synthesis	18:26	Enzymatic modular synthesis and microarray assay of poly-N-acetyllactosamine derivatives.
32579622	1	9	theme	modular	109:115	arg1	strategy					126:133	A facile enzymatic modular assembly strategy	90:133	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	90:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	1	10	theme	varied	226:231	arg1	lengths					233:239	varied lengths	226:239	varied lengths	226:239	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	1	11	theme	assembly	117:124	arg1	strategy					126:133	A facile enzymatic modular assembly strategy	90:133	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	90:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	3	12	theme	fucosylation	563:574	arg1	length					520:525	the length	516:525	the length	516:525	Binding affinities revealed that the avidity of GBPs could be largely affected by the length and the patterns of sialylation and fucosylation.
32579622	3	12	theme	fucosylation	563:574	arg1	patterns					535:542	the patterns	531:542	the patterns of sialylation and fucosylation	531:574	Binding affinities revealed that the avidity of GBPs could be largely affected by the length and the patterns of sialylation and fucosylation.
32579622	2	13	with	interactions	373:384	arg1	panel					393:397	a panel	391:397	a panel of glycan binding proteins (GBPs)	391:431	These glycans were printed as a microarray to investigate their interactions with a panel of glycan binding proteins (GBPs).
32579622	1	14	theme	designed	245:252	arg1	patterns					286:293	designed sialylation and/or fucosylation patterns	245:293	designed sialylation and/or fucosylation patterns	245:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	0	15	theme	microarray	32:41	arg1	assay					43:47	Enzymatic modular synthesis and microarray assay	0:47	assay	43:47	Enzymatic modular synthesis and microarray assay of poly-N-acetyllactosamine derivatives.
32579622	1	16	theme	sialylation	254:264	arg1	patterns					286:293	designed sialylation and/or fucosylation patterns	245:293	designed sialylation and/or fucosylation patterns	245:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	0	17	theme	poly-N-acetyllactosamine	52:75	arg1	derivatives					77:87	poly-N-acetyllactosamine derivatives	52:87	poly-N-acetyllactosamine derivatives	52:87	Enzymatic modular synthesis and microarray assay of poly-N-acetyllactosamine derivatives.
32579622	1	18	theme	preparative-scale	143:159	arg1	synthesis					161:169	the preparative-scale synthesis	139:169	the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	139:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	1	19	with	glycans	213:219	arg1	patterns					286:293	designed sialylation and/or fucosylation patterns	245:293	designed sialylation and/or fucosylation patterns	245:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	1	19	with	glycans	213:219	arg1	lengths					233:239	varied lengths	226:239	varied lengths	226:239	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	1	20	theme	poly-N-acetyllactosamine	174:197	arg1	glycans					213:219	poly-N-acetyllactosamine (poly-LacNAc) glycans	174:219	poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns	174:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	1	21	theme	fucosylation	273:284	arg1	patterns					286:293	designed sialylation and/or fucosylation patterns	245:293	designed sialylation and/or fucosylation patterns	245:293	A facile enzymatic modular assembly strategy for the preparative-scale synthesis of poly-N-acetyllactosamine (poly-LacNAc) glycans with varied lengths and designed sialylation and/or fucosylation patterns is described.
32579622	2	22	theme	proteins	417:424	arg1	panel					393:397	a panel	391:397	a panel of glycan binding proteins (GBPs)	391:431	These glycans were printed as a microarray to investigate their interactions with a panel of glycan binding proteins (GBPs).
32579622	3	23	theme	GBPs	482:485	arg1	avidity					471:477	the avidity	467:477	the avidity of GBPs	467:485	Binding affinities revealed that the avidity of GBPs could be largely affected by the length and the patterns of sialylation and fucosylation.
32579622	0	24	theme	derivatives	77:87	arg1	synthesis					18:26	Enzymatic modular synthesis and microarray assay	0:47	synthesis	18:26	Enzymatic modular synthesis and microarray assay of poly-N-acetyllactosamine derivatives.
32579622	0	24	theme	derivatives	77:87	arg1	assay					43:47	Enzymatic modular synthesis and microarray assay	0:47	assay	43:47	Enzymatic modular synthesis and microarray assay of poly-N-acetyllactosamine derivatives.
32579622	2	25	theme	binding	409:415	arg1	GBPs					427:430	GBPs	427:430	GBPs	427:430	These glycans were printed as a microarray to investigate their interactions with a panel of glycan binding proteins (GBPs).
32579622	2	25	theme	binding	409:415	arg1	proteins					417:424	glycan binding proteins	402:424	glycan binding proteins (GBPs)	402:431	These glycans were printed as a microarray to investigate their interactions with a panel of glycan binding proteins (GBPs).
32281997	5	0	theme	additional	825:834	arg1	staining					836:843	additional staining	825:843	additional staining	825:843	Released glycans are reduced, desalted, purified, and reconstituted, all in 96-well format plates, without additional staining or derivatization.
32281997	4	1	theme	sequential	596:605	arg1	release					607:613	sequential release	596:613	sequential release of N-glycans and O-glycans	596:640	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
32281997	2	2	theme	O-glycomics	383:393	arg1	analysis					355:362	comprehensive analysis	341:362	comprehensive analysis of N-glycomics and O-glycomics	341:393	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	2	3	attach	derived	395:401	arg2	protocols					327:335	The current protocols	315:335	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues	315:424	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	2	3	attach	derived	395:401	arg1	tissues					418:424	tissues	418:424	tissues	418:424	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	2	3	attach	derived	395:401	arg1	cells					408:412	cells	408:412	cells	408:412	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	7	4	theme	glycoprotein	1188:1199	arg1	standards					1201:1209	glycoprotein standards	1188:1209	glycoprotein standards	1188:1209	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	9	5	theme	fetuin	1504:1509	arg1	analysis					1520:1527	the fetuin N-glycan analysis	1500:1527	the fetuin N-glycan analysis	1500:1527	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	6	6	theme	porous	895:900	arg1	chromatography					933:946	porous graphitized carbon nano-liquid chromatography	895:946	porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization	895:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	4	7	theme	96-well	683:689	arg1	format					691:696	96-well format	683:696	96-well format	683:696	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
32281997	10	8	theme	Median	1641:1646	arg1	%					1658:1658	Median CVs of 7.9%	1641:1658	Median CVs of 7.9%	1641:1658	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	10	9	theme	cell	1732:1735	arg1	line					1737:1740	the NMuMG cell line	1722:1740	the NMuMG cell line	1722:1740	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	9	10	theme	analysis	1520:1527	arg1	intraday					1474:1481	intraday	1474:1481	intraday	1474:1481	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	9	10	theme	analysis	1520:1527	arg1	Inter-					1463:1468	Inter-	1463:1468	Inter-	1463:1468	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	1	11	from	diseases	305:312	arg1	cancer					261:266	cancer	261:266	cancer	261:266	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	4	12	from	immobilization	665:678	arg1	format					691:696	96-well format	683:696	96-well format	683:696	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
32281997	6	13	theme	electrospray	1004:1015	arg1	ionization					1017:1026	negative-mode electrospray ionization	990:1026	negative-mode electrospray ionization	990:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	4	14	theme	PVDF	651:654	arg1	immobilization					665:678	PVDF membrane immobilization	651:678	PVDF membrane immobilization in 96-well format from 5 × 105 cells	651:715	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
32281997	5	15	theme	Released	718:725	arg1	glycans					727:733	Released glycans	718:733	Released glycans	718:733	Released glycans are reduced, desalted, purified, and reconstituted, all in 96-well format plates, without additional staining or derivatization.
32281997	2	16	theme	current	319:325	arg1	protocols					327:335	The current protocols	315:335	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues	315:424	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	9	17	theme	intraday	1547:1554	arg1	coefficients					1556:1567	two median intraday coefficients	1536:1567	two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%	1536:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	7	18	gly	glycoprotein	1188:1199	arg1	glycoprotein					1188:1199	glycoprotein standards	1188:1209	glycoprotein standards	1188:1209	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	10	19	theme	of	1652:1653	arg1	%					1658:1658	Median CVs of 7.9%	1641:1658	Median CVs of 7.9%	1641:1658	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	0	20	theme	chromatography-mass	130:148	arg1	spectrometry					150:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	1	21	theme	pathological	235:246	arg1	processes					248:256	pathological processes	235:256	pathological processes in cancer as well as infectious and autoimmune diseases	235:312	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	6	22	theme	mass	966:969	arg1	spectrometry					971:982	tandem mass spectrometry	959:982	tandem mass spectrometry using negative-mode electrospray ionization	959:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	9	23	dep	Inter-	1463:1468	arg1	repeatability					1483:1495	repeatability	1483:1495	repeatability	1483:1495	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	6	24	theme	carbon	914:919	arg1	chromatography					933:946	porous graphitized carbon nano-liquid chromatography	895:946	porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization	895:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	5	25	dep	reduced	739:745	arg1	all					787:789	all	787:789	all	787:789	Released glycans are reduced, desalted, purified, and reconstituted, all in 96-well format plates, without additional staining or derivatization.
32281997	8	26	theme	large	1384:1388	arg1	numbers					1390:1396	relatively large numbers	1373:1396	relatively large numbers of samples	1373:1407	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	6	27	theme	structural	1073:1082	arg1	elucidation					1084:1094	structural elucidation	1073:1094	structural elucidation of glycan species including many compositional isomers	1073:1149	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	7	28	theme	line	1299:1302	arg1	glycosylation					1246:1258	the glycosylation	1242:1258	the glycosylation of the murine mammary gland NMuMG cell line	1242:1302	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	1	29	theme	glycosylation	175:187	arg1	signatures					189:198	glycosylation signatures	175:198	glycosylation signatures of cells	175:207	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	7	30	theme	NMuMG	1288:1292	arg1	line					1299:1302	the murine mammary gland NMuMG cell line	1263:1302	the murine mammary gland NMuMG cell line	1263:1302	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	9	31	theme	%	1604:1604	arg1	CVs					1584:1586	CVs	1584:1586	CVs	1584:1586	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	9	31	theme	%	1604:1604	arg1	variations					1572:1581	variations	1572:1581	variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%	1572:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	10	32	theme	main	1677:1680	arg1	peaks					1682:1686	the main peaks	1673:1686	the main peaks of N- and O-glycans released from the NMuMG cell line	1673:1740	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	8	33	theme	consuming	1424:1432	arg1	way					1434:1436	a less time consuming way	1412:1436	a less time consuming way with high repeatability	1412:1460	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	0	34	theme	porous	97:102	arg1	spectrometry					150:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	1	35	theme	autoimmune	294:303	arg1	diseases					305:312	infectious and autoimmune diseases	279:312	pathological processes in cancer as well as infectious and autoimmune diseases	235:312	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	9	36	theme	median	1613:1618	arg1	CV					1629:1630	a median interday CV	1611:1630	a median interday CV of 9.8%	1611:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	6	37	theme	many	1124:1127	arg1	isomers					1143:1149	many compositional isomers	1124:1149	many compositional isomers	1124:1149	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	2	38	theme	material	469:476	arg1	amount					448:453	a large amount	440:453	a large amount of biological material	440:476	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	2	38	theme	material	469:476	arg1	material					469:476	biological material	458:476	biological material	458:476	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	9	39	theme	CV	1629:1630	arg1	CVs					1584:1586	CVs	1584:1586	CVs	1584:1586	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	9	39	theme	CV	1629:1630	arg1	variations					1572:1581	variations	1572:1581	variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%	1572:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	6	40	theme	species	1106:1112	arg1	resolution					1058:1067	the chromatographic resolution	1038:1067	the chromatographic resolution	1038:1067	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	6	40	theme	species	1106:1112	arg1	elucidation					1084:1094	structural elucidation	1073:1094	structural elucidation of glycan species including many compositional isomers	1073:1149	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	10	41	attach	released	1708:1715	arg1	line					1737:1740	the NMuMG cell line	1722:1740	the NMuMG cell line	1722:1740	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	10	41	attach	released	1708:1715	arg2	N-					1691:1692	N-	1691:1692	N-	1691:1692	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	2	42	theme	large	442:446	arg1	amount					448:453	a large amount	440:453	a large amount of biological material	440:476	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	2	42	theme	large	442:446	arg1	material					469:476	biological material	458:476	biological material	458:476	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	0	43	theme	plate	25:29	arg1	method					50:55	a 96-well plate sample preparation method	15:55	a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry	15:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	10	44	theme	O-glycans	1698:1706	arg1	peaks					1682:1686	the main peaks	1673:1686	the main peaks of N- and O-glycans released from the NMuMG cell line	1673:1740	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	5	45	theme	96-well	794:800	arg1	plates					809:814	96-well format plates	794:814	96-well format plates	794:814	Released glycans are reduced, desalted, purified, and reconstituted, all in 96-well format plates, without additional staining or derivatization.
32281997	10	46	theme	N-	1691:1692	arg1	peaks					1682:1686	the main peaks	1673:1686	the main peaks of N- and O-glycans released from the NMuMG cell line	1673:1740	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	4	47	theme	N-glycans	618:626	arg1	release					607:613	sequential release	596:613	sequential release of N-glycans and O-glycans	596:640	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
32281997	7	48	gly	glycosylation	1246:1258	arg1	line					1299:1302	the murine mammary gland NMuMG cell line	1263:1302	the murine mammary gland NMuMG cell line	1263:1302	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	3	49	theme	samples	542:548	arg1	numbers					531:537	very limited numbers	518:537	very limited numbers of samples	518:548	They also only allow the processing of very limited numbers of samples at a time.
32281997	4	50	theme	O-glycans	632:640	arg1	release					607:613	sequential release	596:613	sequential release of N-glycans and O-glycans	596:640	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
32281997	3	51	theme	numbers	531:537	arg1	processing					504:513	the processing	500:513	the processing of very limited numbers of samples	500:548	They also only allow the processing of very limited numbers of samples at a time.
32281997	6	52	theme	nano-liquid	921:931	arg1	chromatography					933:946	porous graphitized carbon nano-liquid chromatography	895:946	porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization	895:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	1	53	theme	infectious	279:288	arg1	diseases					305:312	infectious and autoimmune diseases	279:312	pathological processes in cancer as well as infectious and autoimmune diseases	235:312	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	6	54	theme	graphitized	902:912	arg1	chromatography					933:946	porous graphitized carbon nano-liquid chromatography	895:946	porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization	895:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	9	55	theme	N-glycan	1511:1518	arg1	analysis					1520:1527	the fetuin N-glycan analysis	1500:1527	the fetuin N-glycan analysis	1500:1527	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	0	56	theme	preparation	38:48	arg1	method					50:55	a 96-well plate sample preparation method	15:55	a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry	15:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	8	57	theme	developed	1309:1317	arg1	protocol					1319:1326	The developed protocol	1305:1326	The developed protocol	1305:1326	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	2	58	theme	comprehensive	341:353	arg1	analysis					355:362	comprehensive analysis	341:362	comprehensive analysis of N-glycomics and O-glycomics	341:393	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	1	59	theme	cells	203:207	arg1	signatures					189:198	glycosylation signatures	175:198	glycosylation signatures of cells	175:207	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	0	60	theme	liquid	123:128	arg1	spectrometry					150:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	10	61	theme	good	1758:1761	arg1	repeatability					1763:1775	a very good repeatability	1751:1775	a very good repeatability	1751:1775	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	8	62	dep	consuming	1424:1432	arg1	time					1419:1422	time	1419:1422	time	1419:1422	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	6	63	theme	negative-mode	990:1002	arg1	ionization					1017:1026	negative-mode electrospray ionization	990:1026	negative-mode electrospray ionization	990:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	2	64	theme	N-glycomics	367:377	arg1	analysis					355:362	comprehensive analysis	341:362	comprehensive analysis of N-glycomics and O-glycomics	341:393	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	8	65	theme	N-	1351:1352	arg1	analysis					1339:1346	the analysis	1335:1346	the analysis of N- and O-glycans from relatively large numbers of samples	1335:1407	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	10	66	theme	CVs	1648:1650	arg1	%					1658:1658	Median CVs of 7.9%	1641:1658	Median CVs of 7.9%	1641:1658	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	9	67	theme	variations	1572:1581	arg1	coefficients					1556:1567	two median intraday coefficients	1536:1567	two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%	1536:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	6	68	theme	tandem	959:964	arg1	spectrometry					971:982	tandem mass spectrometry	959:982	tandem mass spectrometry using negative-mode electrospray ionization	959:1026	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	8	69	theme	O-glycans	1358:1366	arg1	analysis					1339:1346	the analysis	1335:1346	the analysis of N- and O-glycans from relatively large numbers of samples	1335:1407	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	11	70	theme	purified	1806:1813	arg1	glycoproteins					1815:1827	purified glycoproteins	1806:1827	purified glycoproteins	1806:1827	The method is applicable to purified glycoproteins as well as to biofluids and cell- or tissue-based samples.
32281997	1	71	from	processes	248:256	arg1	cancer					261:266	cancer	261:266	cancer	261:266	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	0	72	theme	integrated	61:70	arg1	N-					72:73	N-	72:73	N-	72:73	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	9	73	theme	median	1540:1545	arg1	coefficients					1556:1567	two median intraday coefficients	1536:1567	two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%	1536:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	7	74	theme	cell	1294:1297	arg1	line					1299:1302	the murine mammary gland NMuMG cell line	1263:1302	the murine mammary gland NMuMG cell line	1263:1302	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	11	75	theme	cell-	1857:1861	arg1	samples					1879:1885	cell- or tissue-based samples	1857:1885	cell- or tissue-based samples	1857:1885	The method is applicable to purified glycoproteins as well as to biofluids and cell- or tissue-based samples.
32281997	8	76	from	analysis	1339:1346	arg1	numbers					1390:1396	relatively large numbers	1373:1396	relatively large numbers of samples	1373:1407	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	9	77	theme	%	1595:1595	arg1	CVs					1584:1586	CVs	1584:1586	CVs	1584:1586	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	9	77	theme	%	1595:1595	arg1	variations					1572:1581	variations	1572:1581	variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%	1572:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	6	78	theme	chromatographic	1042:1056	arg1	resolution					1058:1067	the chromatographic resolution	1038:1067	the chromatographic resolution	1038:1067	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	0	79	theme	carbon	116:121	arg1	spectrometry					150:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	8	80	theme	samples	1401:1407	arg1	numbers					1390:1396	relatively large numbers	1373:1396	relatively large numbers of samples	1373:1407	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	7	81	theme	gland	1282:1286	arg1	line					1299:1302	the murine mammary gland NMuMG cell line	1263:1302	the murine mammary gland NMuMG cell line	1263:1302	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	8	82	with	way	1434:1436	arg1	repeatability					1448:1460	high repeatability	1443:1460	high repeatability	1443:1460	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	0	83	theme	graphitized	104:114	arg1	spectrometry					150:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	porous graphitized carbon liquid chromatography-mass spectrometry	97:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	1	84	from	Changes	164:170	arg1	signatures					189:198	glycosylation signatures	175:198	glycosylation signatures of cells	175:207	Changes in glycosylation signatures of cells have been associated with pathological processes in cancer as well as infectious and autoimmune diseases.
32281997	7	85	theme	murine	1267:1272	arg1	line					1299:1302	the murine mammary gland NMuMG cell line	1263:1302	the murine mammary gland NMuMG cell line	1263:1302	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	5	86	theme	format	802:807	arg1	plates					809:814	96-well format plates	794:814	96-well format plates	794:814	Released glycans are reduced, desalted, purified, and reconstituted, all in 96-well format plates, without additional staining or derivatization.
32281997	6	87	theme	compositional	1129:1141	arg1	isomers					1143:1149	many compositional isomers	1124:1149	many compositional isomers	1124:1149	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	0	88	theme	96-well	17:23	arg1	method					50:55	a 96-well plate sample preparation method	15:55	a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry	15:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	8	89	from	numbers	1390:1396	arg1	O-glycans					1358:1366	O-glycans	1358:1366	O-glycans	1358:1366	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	8	89	from	numbers	1390:1396	arg1	N-					1351:1352	N-	1351:1352	N-	1351:1352	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	8	89	from	numbers	1390:1396	arg1	analysis					1339:1346	the analysis	1335:1346	the analysis of N- and O-glycans from relatively large numbers of samples	1335:1407	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	9	90	theme	interday	1620:1627	arg1	CV					1629:1630	a median interday CV	1611:1630	a median interday CV of 9.8%	1611:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	2	91	theme	biological	458:467	arg1	material					469:476	biological material	458:476	biological material	458:476	The current protocols for comprehensive analysis of N-glycomics and O-glycomics derived from cells and tissues often require a large amount of biological material.
32281997	8	92	theme	high	1443:1446	arg1	repeatability					1448:1460	high repeatability	1443:1460	high repeatability	1443:1460	The developed protocol allows the analysis of N- and O-glycans from relatively large numbers of samples in a less time consuming way with high repeatability.
32281997	10	93	theme	NMuMG	1726:1730	arg1	line					1737:1740	the NMuMG cell line	1722:1740	the NMuMG cell line	1722:1740	Median CVs of 7.9% and 8.7% for the main peaks of N- and O-glycans released from the NMuMG cell line indicate a very good repeatability.
32281997	0	94	theme	sample	31:36	arg1	method					50:55	a 96-well plate sample preparation method	15:55	a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry	15:161	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	6	95	theme	glycan	1099:1104	arg1	species					1106:1112	glycan species	1099:1112	glycan species including many compositional isomers	1099:1149	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	6	95	theme	glycan	1099:1104	arg1	isomers					1143:1149	many compositional isomers	1124:1149	many compositional isomers	1124:1149	Glycans are then analyzed with porous graphitized carbon nano-liquid chromatography coupled to tandem mass spectrometry using negative-mode electrospray ionization, enabling the chromatographic resolution and structural elucidation of glycan species including many compositional isomers.
32281997	11	96	gly	glycoproteins	1815:1827	arg1	glycoproteins					1815:1827	purified glycoproteins	1806:1827	purified glycoproteins	1806:1827	The method is applicable to purified glycoproteins as well as to biofluids and cell- or tissue-based samples.
32281997	7	97	theme	mammary	1274:1280	arg1	line					1299:1302	the murine mammary gland NMuMG cell line	1263:1302	the murine mammary gland NMuMG cell line	1263:1302	The approach was demonstrated using glycoprotein standards and further applied to analyze the glycosylation of the murine mammary gland NMuMG cell line.
32281997	0	98	theme	method	50:55	arg1	Development					0:10	Development	0:10	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.	0:162	Development of a 96-well plate sample preparation method for integrated N- and O-glycomics using porous graphitized carbon liquid chromatography-mass spectrometry.
32281997	9	99	theme	%	1638:1638	arg1	%					1638:1638	9.8%	1635:1638	9.8%	1635:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	9	99	theme	%	1638:1638	arg1	%					1595:1595	7.6%	1592:1595	7.6%	1592:1595	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	9	99	theme	%	1638:1638	arg1	%					1604:1604	8.0%	1601:1604	8.0%	1601:1604	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	9	99	theme	%	1638:1638	arg1	CV					1629:1630	a median interday CV	1611:1630	a median interday CV of 9.8%	1611:1638	Inter- and intraday repeatability of the fetuin N-glycan analysis showed two median intraday coefficients of variations (CVs) of 7.6% and 8.0%, and a median interday CV of 9.8%.
32281997	3	100	theme	limited	523:529	arg1	numbers					531:537	very limited numbers	518:537	very limited numbers of samples	518:548	They also only allow the processing of very limited numbers of samples at a time.
32281997	4	101	theme	membrane	656:663	arg1	immobilization					665:678	PVDF membrane immobilization	651:678	PVDF membrane immobilization in 96-well format from 5 × 105 cells	651:715	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
32281997	11	102	theme	tissue-based	1866:1877	arg1	samples					1879:1885	cell- or tissue-based samples	1857:1885	cell- or tissue-based samples	1857:1885	The method is applicable to purified glycoproteins as well as to biofluids and cell- or tissue-based samples.
32281997	4	103	from	cells	711:715	arg1	immobilization					665:678	PVDF membrane immobilization	651:678	PVDF membrane immobilization in 96-well format from 5 × 105 cells	651:715	Here we established a workflow for sequential release of N-glycans and O-glycans based on PVDF membrane immobilization in 96-well format from 5 × 105 cells.
31860772	7	0	theme	fluid	1359:1363	arg1	regions					1365:1371	the cyst fluid regions	1350:1371	the cyst fluid regions	1350:1371	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	7	1	theme	disease	1237:1243	arg1	tissue					1245:1250	A polycystic kidney disease tissue	1217:1250	A polycystic kidney disease tissue	1217:1250	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	1	2	theme	frequent	246:253	arg1	recurrence					263:272	frequent disease recurrence	246:272	frequent disease recurrence	246:272	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	7	3	theme	polycystic	1219:1228	arg1	disease					1237:1243	A polycystic kidney disease	1217:1243	A polycystic kidney disease tissue	1217:1250	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	10	4	theme	new	1957:1959	arg1	interventions					1973:1985	new therapeutic interventions	1957:1985	new therapeutic interventions	1957:1985	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	4	5	theme	kidney	719:724	arg1	samples					733:739	normal kidney tissue samples	712:739	normal kidney tissue samples	712:739	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	2	6	theme	well-described	302:315	arg1	effect					325:330	a well-described Warburg effect	300:330	a well-described Warburg effect	300:330	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	5	7	theme	multiantennary	936:949	arg1	N-glycans					951:959	abundant multiantennary N-glycans	927:959	abundant multiantennary N-glycans	927:959	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	6	8	theme	ccRCC	1055:1059	arg1	tissues					1061:1067	ccRCC tissues	1055:1067	ccRCC tissues	1055:1067	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	5	9	theme	proximal	888:895	arg1	tubule					897:902	the proximal tubule	884:902	the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues	884:1024	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	1	10	theme	renal	115:119	arg1	ccRCC					137:141	ccRCC	137:141	ccRCC	137:141	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	1	10	theme	renal	115:119	arg1	carcinoma					126:134	Clear-cell renal cell carcinoma	104:134	Clear-cell renal cell carcinoma (ccRCC)	104:142	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	8	11	theme	mass	1403:1406	arg1	spectrometry					1408:1419	the imaging mass spectrometry	1391:1419	the imaging mass spectrometry	1391:1419	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	10	12	theme	striking	1774:1781	arg1	differences					1783:1793	These striking differences	1768:1793	These striking differences in glycosylation associated with ccRCC	1768:1832	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	10	13	theme	diagnostic	1991:2000	arg1	markers					2002:2008	diagnostic markers	1991:2008	diagnostic markers	1991:2008	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	3	14	theme	nontumor	617:624	arg1	regions					626:632	tumor and nontumor regions	607:632	tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays	607:698	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	5	15	theme	multziple	1000:1008	arg1	residues					1017:1024	multziple fucose residues	1000:1024	multziple fucose residues	1000:1024	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	4	16	theme	glycan-based	774:785	arg1	distinctions					787:798	N-linked glycan-based distinctions	765:798	N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features	765:864	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	3	17	theme	specimens	667:675	arg1	regions					626:632	tumor and nontumor regions	607:632	tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays	607:698	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	5	18	theme	fucose	1010:1015	arg1	residues					1017:1024	multziple fucose residues	1000:1024	multziple fucose residues	1000:1024	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	4	19	theme	samples	733:739	arg1	Regions					701:707	Regions	701:707	Regions of normal kidney tissue samples	701:739	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	9	20	theme	transcript	1569:1578	arg1	levels					1580:1585	The transcript levels	1565:1585	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae	1565:1677	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	9	21	theme	FUT3	1594:1597	arg1	genes					1608:1612	the FUT3 and FUT6 genes	1590:1612	the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae	1590:1677	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	0	22	theme	human	13:17	arg1	N-glycome					26:34	the human kidney N-glycome	9:34	the human kidney N-glycome in normal and cancer tissues	9:63	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	8	23	theme	gene	1466:1469	arg1	data					1477:1480	transcriptomic gene array data	1451:1480	transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes	1451:1562	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	6	24	theme	multiple	1076:1083	arg1	N-glycans					1100:1108	multiple tumor-specific N-glycans	1076:1108	multiple tumor-specific N-glycans	1076:1108	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	8	25	theme	data	1477:1480	arg1	analyses					1421:1428	Complementary to the imaging mass spectrometry analyses	1374:1428	Complementary to the imaging mass spectrometry analyses	1374:1428	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	8	25	theme	data	1477:1480	arg1	assessment					1437:1446	an assessment	1434:1446	an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes	1434:1562	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	0	26	theme	imaging	77:83	arg1	spectrometry					90:101	MALDI imaging mass spectrometry	71:101	MALDI imaging mass spectrometry	71:101	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	7	27	theme	specific	1306:1313	arg1	glycans					1330:1336	specific nonfucosylated glycans	1306:1336	specific nonfucosylated glycans detected in the cyst fluid regions	1306:1371	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	9	28	theme	N-glycan	1661:1668	arg1	antennae					1670:1677	N-glycan antennae	1661:1677	N-glycan antennae	1661:1677	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	0	29	from	N-glycome	26:34	arg1	cancer					50:55	cancer	50:55	cancer	50:55	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	0	29	from	N-glycome	26:34	arg1	normal					39:44	normal	39:44	normal	39:44	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	8	30	theme	fucosyltransferase	1497:1514	arg1	family					1521:1526	the fucosyltransferase gene family	1493:1526	the fucosyltransferase gene family	1493:1526	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	2	31	theme	complex	377:383	arg1	synthesis					398:406	complex carbohydrate synthesis	377:406	complex carbohydrate synthesis	377:406	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	9	32	theme	ccRCC	1715:1719	arg1	tissues					1721:1727	all ccRCC tissues	1711:1727	all ccRCC tissues relative to matching nontumor tissues	1711:1765	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	2	33	theme	cell	439:442	arg1	glycosylation					452:464	cell surface glycosylation	439:464	cell surface glycosylation	439:464	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	7	34	theme	N-glycan	1279:1286	arg1	composition					1288:1298	N-glycan composition	1279:1298	N-glycan composition	1279:1298	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	9	35	theme	relative	1729:1736	arg1	tissues					1721:1727	all ccRCC tissues	1711:1727	all ccRCC tissues relative to matching nontumor tissues	1711:1765	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	6	36	theme	tetra-antennary	1138:1152	arg1	structures					1154:1163	tri- and tetra-antennary structures	1129:1163	tri- and tetra-antennary structures	1129:1163	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	6	37	from	tissues	1061:1067	arg1	absent					1045:1050	absent	1045:1050	absent	1045:1050	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	8	38	theme	other	1532:1536	arg1	genes					1558:1562	other glycosyltransferase genes	1532:1562	other glycosyltransferase genes	1532:1562	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	2	39	contain	has	296:298	arg1	ccRCC					290:294	ccRCC	290:294	ccRCC	290:294	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	2	39	contain	has	296:298	arg2	utilization					332:342	utilization	332:342	utilization of glucose	332:353	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	0	40	dep	normal	39:44	arg1	tissues					57:63	tissues	57:63	tissues	57:63	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	6	41	theme	tri-	1129:1132	arg1	structures					1154:1163	tri- and tetra-antennary structures	1129:1163	tri- and tetra-antennary structures	1129:1163	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	3	42	theme	tissue	681:686	arg1	microarrays					688:698	tissue microarrays	681:698	tissue microarrays	681:698	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	2	43	theme	glucose	347:353	arg1	utilization					332:342	utilization	332:342	utilization of glucose	332:353	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	5	44	with	detection	914:922	arg1	N-acetylglucosamine					976:994	bisecting N-acetylglucosamine	966:994	bisecting N-acetylglucosamine	966:994	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	5	44	with	detection	914:922	arg1	residues					1017:1024	multziple fucose residues	1000:1024	multziple fucose residues	1000:1024	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	5	45	dep	tubule	897:902	arg1	notable					872:878	notable	872:878	notable	872:878	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	8	46	theme	Complementary	1374:1386	arg1	analyses					1421:1428	Complementary to the imaging mass spectrometry analyses	1374:1428	Complementary to the imaging mass spectrometry analyses	1374:1428	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	8	46	theme	Complementary	1374:1386	arg1	assessment					1437:1446	an assessment	1434:1446	an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes	1434:1562	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	10	47	theme	mechanistic	1852:1862	arg1	insight					1864:1870	new mechanistic insight	1848:1870	new mechanistic insight into the glycobiology underpinning kidney malignancies	1848:1925	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	10	48	theme	kidney	1907:1912	arg1	malignancies					1914:1925	kidney malignancies	1907:1925	kidney malignancies	1907:1925	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	6	49	theme	sialylation	1204:1214	arg1	structures					1154:1163	tri- and tetra-antennary structures	1129:1163	tri- and tetra-antennary structures	1129:1163	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	6	49	theme	sialylation	1204:1214	arg1	levels					1177:1182	varying levels	1169:1182	varying levels of fucosylation and sialylation	1169:1214	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	7	50	theme	kidney	1230:1235	arg1	disease					1237:1243	A polycystic kidney disease	1217:1243	A polycystic kidney disease tissue	1217:1250	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	7	51	located	detected	1338:1345	arg2	glycans					1330:1336	specific nonfucosylated glycans	1306:1336	specific nonfucosylated glycans detected in the cyst fluid regions	1306:1371	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	7	51	located	detected	1338:1345	arg1	regions					1365:1371	the cyst fluid regions	1350:1371	the cyst fluid regions	1350:1371	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	3	52	theme	spectrometry	507:518	arg1	approach					520:527	an imaging mass spectrometry approach	491:527	an imaging mass spectrometry approach	491:527	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	6	53	theme	fucosylation	1187:1198	arg1	structures					1154:1163	tri- and tetra-antennary structures	1129:1163	tri- and tetra-antennary structures	1129:1163	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	6	53	theme	fucosylation	1187:1198	arg1	levels					1177:1182	varying levels	1169:1182	varying levels of fucosylation and sialylation	1169:1214	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	3	54	theme	compositional	559:571	arg1	differences					573:583	compositional differences	559:583	compositional differences	559:583	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	1	55	theme	disease	255:261	arg1	recurrence					263:272	frequent disease recurrence	246:272	frequent disease recurrence	246:272	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	10	56	theme	therapeutic	1961:1971	arg1	interventions					1973:1985	new therapeutic interventions	1957:1985	new therapeutic interventions	1957:1985	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	4	57	link	N-linked	765:772	arg1	distinctions					787:798	N-linked glycan-based distinctions	765:798	N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features	765:864	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	3	58	theme	imaging	494:500	arg1	approach					520:527	an imaging mass spectrometry approach	491:527	an imaging mass spectrometry approach	491:527	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	5	59	theme	abundant	927:934	arg1	N-glycans					951:959	abundant multiantennary N-glycans	927:959	abundant multiantennary N-glycans	927:959	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	10	60	from	differences	1783:1793	arg1	glycosylation					1798:1810	glycosylation	1798:1810	glycosylation associated with ccRCC	1798:1832	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	2	61	theme	Warburg	317:323	arg1	effect					325:330	a well-described Warburg effect	300:330	a well-described Warburg effect	300:330	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	1	62	theme	clinical	167:174	arg1	management					176:185	clinical management	167:185	clinical management	167:185	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	4	63	theme	normal	712:717	arg1	samples					733:739	normal kidney tissue samples	712:739	normal kidney tissue samples	712:739	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	3	64	dep	formalin-fixed	637:650	arg1	clinical					652:659	clinical	652:659	clinical	652:659	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	3	65	theme	tumor	607:611	arg1	regions					626:632	tumor and nontumor regions	607:632	tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays	607:698	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	9	66	theme	matching	1741:1748	arg1	tissues					1759:1765	matching nontumor tissues	1741:1765	matching nontumor tissues	1741:1765	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	1	67	theme	late-stage	198:207	arg1	detection					209:217	late-stage detection	198:217	late-stage detection	198:217	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	8	68	theme	imaging	1395:1401	arg1	spectrometry					1408:1419	the imaging mass spectrometry	1391:1419	the imaging mass spectrometry	1391:1419	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	7	69	theme	nonfucosylated	1315:1328	arg1	glycans					1330:1336	specific nonfucosylated glycans	1306:1336	specific nonfucosylated glycans detected in the cyst fluid regions	1306:1371	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	1	70	theme	Clear-cell	104:113	arg1	ccRCC					137:141	ccRCC	137:141	ccRCC	137:141	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	1	70	theme	Clear-cell	104:113	arg1	carcinoma					126:134	Clear-cell renal cell carcinoma	104:134	Clear-cell renal cell carcinoma (ccRCC)	104:142	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	4	71	theme	proximal	841:848	arg1	features					857:864	proximal tubule features	841:864	proximal tubule features	841:864	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	3	72	theme	ccRCC	661:665	arg1	specimens					667:675	formalin-fixed clinical ccRCC specimens	637:675	formalin-fixed clinical ccRCC specimens	637:675	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	1	73	theme	cell	121:124	arg1	ccRCC					137:141	ccRCC	137:141	ccRCC	137:141	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	1	73	theme	cell	121:124	arg1	carcinoma					126:134	Clear-cell renal cell carcinoma	104:134	Clear-cell renal cell carcinoma (ccRCC)	104:142	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	4	74	theme	N-linked	765:772	arg1	distinctions					787:798	N-linked glycan-based distinctions	765:798	N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features	765:864	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	3	75	theme	formalin-fixed	637:650	arg1	specimens					667:675	formalin-fixed clinical ccRCC specimens	637:675	formalin-fixed clinical ccRCC specimens	637:675	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	9	76	theme	FUT6	1603:1606	arg1	genes					1608:1612	the FUT3 and FUT6 genes	1590:1612	the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae	1590:1677	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	5	77	theme	N-glycans	951:959	arg1	detection					914:922	detection	914:922	detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues	914:1024	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	4	78	theme	tissue	726:731	arg1	samples					733:739	normal kidney tissue samples	712:739	normal kidney tissue samples	712:739	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	0	79	theme	MALDI	71:75	arg1	spectrometry					90:101	MALDI imaging mass spectrometry	71:101	MALDI imaging mass spectrometry	71:101	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	5	80	theme	bisecting	966:974	arg1	N-acetylglucosamine					976:994	bisecting N-acetylglucosamine	966:994	bisecting N-acetylglucosamine	966:994	Most notable was the proximal tubule localized detection of abundant multiantennary N-glycans with bisecting N-acetylglucosamine and multziple fucose residues.
31860772	6	81	theme	tumor-specific	1085:1098	arg1	N-glycans					1100:1108	multiple tumor-specific N-glycans	1076:1108	multiple tumor-specific N-glycans	1076:1108	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	8	82	theme	transcriptomic	1451:1464	arg1	data					1477:1480	transcriptomic gene array data	1451:1480	transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes	1451:1562	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	0	83	theme	mass	85:88	arg1	spectrometry					90:101	MALDI imaging mass spectrometry	71:101	MALDI imaging mass spectrometry	71:101	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	8	84	theme	array	1471:1475	arg1	data					1477:1480	transcriptomic gene array data	1451:1480	transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes	1451:1562	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	7	85	gly	nonfucosylated	1315:1328	arg1	glycans					1330:1336	specific nonfucosylated glycans	1306:1336	specific nonfucosylated glycans detected in the cyst fluid regions	1306:1371	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	9	86	theme	genes	1608:1612	arg1	levels					1580:1585	The transcript levels	1565:1585	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae	1565:1677	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	2	87	theme	carbohydrate	385:396	arg1	synthesis					398:406	complex carbohydrate synthesis	377:406	complex carbohydrate synthesis	377:406	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	6	88	theme	varying	1169:1175	arg1	levels					1177:1182	varying levels	1169:1182	varying levels of fucosylation and sialylation	1169:1214	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	2	89	theme	surface	444:450	arg1	glycosylation					452:464	cell surface glycosylation	439:464	cell surface glycosylation	439:464	Metabolically, ccRCC has a well-described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined.
31860772	0	90	theme	kidney	19:24	arg1	N-glycome					26:34	the human kidney N-glycome	9:34	the human kidney N-glycome in normal and cancer tissues	9:63	Defining the human kidney N-glycome in normal and cancer tissues using MALDI imaging mass spectrometry.
31860772	6	91	from	absent	1045:1050	arg1	tissues					1061:1067	ccRCC tissues	1055:1067	ccRCC tissues	1055:1067	These glycans are absent in ccRCC tissues, while multiple tumor-specific N-glycans were detected with tri- and tetra-antennary structures and varying levels of fucosylation and sialylation.
31860772	3	92	theme	microarrays	688:698	arg1	regions					626:632	tumor and nontumor regions	607:632	tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays	607:698	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	8	93	theme	gene	1516:1519	arg1	family					1521:1526	the fucosyltransferase gene family	1493:1526	the fucosyltransferase gene family	1493:1526	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	9	94	theme	responsible	1614:1624	arg1	genes					1608:1612	the FUT3 and FUT6 genes	1590:1612	the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae	1590:1677	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	9	95	theme	nontumor	1750:1757	arg1	tissues					1759:1765	matching nontumor tissues	1741:1765	matching nontumor tissues	1741:1765	The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N-glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues.
31860772	8	96	theme	glycosyltransferase	1538:1556	arg1	genes					1558:1562	other glycosyltransferase genes	1532:1562	other glycosyltransferase genes	1532:1562	Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes.
31860772	3	97	theme	mass	502:505	arg1	approach					520:527	an imaging mass spectrometry approach	491:527	an imaging mass spectrometry approach	491:527	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
31860772	10	98	theme	new	1848:1850	arg1	insight					1864:1870	new mechanistic insight	1848:1870	new mechanistic insight into the glycobiology underpinning kidney malignancies	1848:1925	These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers.
31860772	1	99	theme	treatment	220:228	arg1	resistance					230:239	treatment resistance	220:239	treatment resistance	220:239	Clear-cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late-stage detection, treatment resistance, and frequent disease recurrence.
31860772	7	100	theme	cyst	1354:1357	arg1	regions					1365:1371	the cyst fluid regions	1350:1371	the cyst fluid regions	1350:1371	A polycystic kidney disease tissue was also characterized for N-glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions.
31860772	4	101	theme	tubule	850:855	arg1	features					857:864	proximal tubule features	841:864	proximal tubule features	841:864	Regions of normal kidney tissue samples were also evaluated for N-linked glycan-based distinctions between cortex, medullar, glomeruli, and proximal tubule features.
31860772	3	102	theme	N-glycosylation	530:544	arg1	patterns					546:553	N-glycosylation patterns	530:553	N-glycosylation patterns	530:553	Using an imaging mass spectrometry approach, N-glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin-fixed clinical ccRCC specimens and tissue microarrays.
33677548	0	0	theme	glycoconjugate	75:88	arg1	data					90:93	glycoconjugate data	75:93	glycoconjugate data	75:93	The glycoconjugate ontology (GlycoCoO) for standardizing the annotation of glycoconjugate data and its application.
33677548	6	1	theme	data	1195:1198	arg1	formats					1209:1215	data exchange formats	1195:1215	data exchange formats	1195:1215	GlycoCoO can be used to represent glycoproteomics data in triplestores and can serve as a basis for data exchange formats.
33677548	7	2	dep	https	1302:1306	arg1	//github.com/glycoinfo/GlycoCoO					1308:1338	//github.com/glycoinfo/GlycoCoO	1308:1338	//github.com/glycoinfo/GlycoCoO	1308:1338	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	6	3	from	data	1145:1148	arg1	triplestores					1153:1164	triplestores	1153:1164	triplestores	1153:1164	GlycoCoO can be used to represent glycoproteomics data in triplestores and can serve as a basis for data exchange formats.
33677548	4	4	theme	experimental	567:578	arg1	method					580:585	the experimental method	563:585	the experimental method	563:585	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	5	5	theme	glycoproteomics	1073:1087	arg1	data					1089:1092	glycoproteomics data	1073:1092	glycoproteomics data	1073:1092	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	1	6	from	advances	145:152	arg1	development					161:171	the development	157:171	the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites	157:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	3	7	with	glycoproteins	490:502	arg1	glycans					541:547	glycans	541:547	glycans	541:547	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	6	8	theme	glycoproteomics	1129:1143	arg1	data					1145:1148	glycoproteomics data	1129:1148	glycoproteomics data in triplestores	1129:1164	GlycoCoO can be used to represent glycoproteomics data in triplestores and can serve as a basis for data exchange formats.
33677548	1	9	theme	reporting	257:265	arg1	proteins					267:274	the reporting proteins	253:274	the reporting proteins	253:274	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	0	10	theme	data	90:93	arg1	annotation					61:70	the annotation	57:70	the annotation of glycoconjugate data and its application	57:113	The glycoconjugate ontology (GlycoCoO) for standardizing the annotation of glycoconjugate data and its application.
33677548	5	11	theme	semantic	1028:1035	arg1	framework					1037:1045	a standard semantic framework	1017:1045	a standard semantic framework to describe and represent glycoproteomics data	1017:1092	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	5	11	theme	semantic	1028:1035	arg1	Ontology					994:1001	the GlycoConjugate Ontology	975:1001	the GlycoConjugate Ontology (GlycoCoO)	975:1012	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	3	12	gly	glycoproteins	490:502	arg1	glycoproteins					490:502	glycoproteins	490:502	glycoproteins	490:502	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	0	13	theme	application	103:113	arg1	annotation					61:70	the annotation	57:70	the annotation of glycoconjugate data and its application	57:113	The glycoconjugate ontology (GlycoCoO) for standardizing the annotation of glycoconjugate data and its application.
33677548	6	14	theme	exchange	1200:1207	arg1	formats					1209:1215	data exchange formats	1195:1215	data exchange formats	1195:1215	GlycoCoO can be used to represent glycoproteomics data in triplestores and can serve as a basis for data exchange formats.
33677548	4	15	from	glycoforms	730:739	arg1	deal					775:778	deal	775:778	deal with partially missing site information if no site mapping was performed	775:851	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	15	from	glycoforms	730:739	arg1	side					769:772	a specific glycosylation side	744:772	a specific glycosylation side	744:772	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	16	theme	specific	746:753	arg1	deal					775:778	deal	775:778	deal with partially missing site information if no site mapping was performed	775:851	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	16	theme	specific	746:753	arg1	side					769:772	a specific glycosylation side	744:772	a specific glycosylation side	744:772	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	17	dep	deal	775:778	arg1	performed					843:851	performed	843:851	was performed	839:851	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	18	with	deal	775:778	arg1	information					808:818	partially missing site information	785:818	partially missing site information	785:818	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	3	19	theme	challenging	512:522	arg1	annotations					524:534	the challenging annotations	508:534	the challenging annotations	508:534	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	0	20	theme	glycoconjugate	4:17	arg1	ontology					19:26	The glycoconjugate ontology	0:26	The glycoconjugate ontology (GlycoCoO) for standardizing the annotation of glycoconjugate data and its application.	0:114	The glycoconjugate ontology (GlycoCoO) for standardizing the annotation of glycoconjugate data and its application.
33677548	0	20	theme	glycoconjugate	4:17	arg1	GlycoCoO					29:36	GlycoCoO	29:36	GlycoCoO	29:36	The glycoconjugate ontology (GlycoCoO) for standardizing the annotation of glycoconjugate data and its application.
33677548	4	21	theme	site	826:829	arg1	mapping					831:837	no site mapping	823:837	no site mapping	823:837	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	22	theme	site	929:932	arg1	glycoform					905:913	a glycoform	903:913	a glycoform of a specific site	903:932	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	7	23	theme	supporting	1255:1264	arg1	providers					1241:1249	database providers	1232:1249	database providers	1232:1249	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	23	theme	supporting	1255:1264	arg1	documentation					1266:1278	supporting documentation	1255:1278	supporting documentation	1255:1278	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	23	theme	supporting	1255:1264	arg1	online					1294:1299	online	1294:1299	online	1294:1299	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	23	theme	supporting	1255:1264	arg1	ontology					1222:1229	The ontology	1218:1229	The ontology	1218:1229	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	4	24	gly	glycoform	905:913	arg1	site					929:932	a specific site	918:932	a specific site	918:932	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	6	25	used	used	1111:1114	arg2	basis					1185:1189	a basis	1183:1189	a basis for data exchange formats	1183:1215	GlycoCoO can be used to represent glycoproteomics data in triplestores and can serve as a basis for data exchange formats.
33677548	6	25	used	used	1111:1114	arg2	GlycoCoO					1095:1102	GlycoCoO	1095:1102	GlycoCoO	1095:1102	GlycoCoO can be used to represent glycoproteomics data in triplestores and can serve as a basis for data exchange formats.
33677548	1	26	theme	glycoproteomics	176:190	arg1	protocols					192:200	glycoproteomics protocols	176:200	glycoproteomics protocols	176:200	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	1	27	theme	protocols	192:200	arg1	development					161:171	the development	157:171	the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites	157:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	1	28	theme	attached	283:290	arg1	glycans					292:298	their attached glycans	277:298	their attached glycans	277:298	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	4	29	dep	store	681:685	arg1	just					691:694	just	691:694	just	691:694	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	2	30	theme	data	398:401	arg1	repositories					403:414	data repositories	398:414	data repositories	398:414	However, only very few of these reports find their way into databases or data repositories.
33677548	1	31	theme	Recent	116:121	arg1	years					123:127	Recent years	116:127	Recent years	116:127	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	3	32	theme	major	428:432	arg1	reasons					434:440	the major reasons	424:440	the major reasons	424:440	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	4	33	theme	complete	641:648	arg1	structures					650:659	complete structures	641:659	complete structures	641:659	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	1	34	theme	methods	206:212	arg1	development					161:171	the development	157:171	the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites	157:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	4	35	theme	as	664:665	arg1	compositions					667:678	as compositions	664:678	as compositions	664:678	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	36	theme	glycans	888:894	arg1	abundances					864:873	abundances	864:873	abundances	864:873	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	36	theme	glycans	888:894	arg1	ratios					878:883	ratios	878:883	ratios	878:883	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	3	37	theme	reasons	434:440	arg1	reasons					434:440	the major reasons	424:440	the major reasons	424:440	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	3	37	theme	reasons	434:440	arg1	absence					449:455	the absence	445:455	the absence of digital standard to represent glycoproteins and the challenging annotations with glycans	445:547	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	3	37	theme	reasons	434:440	arg1	One					417:419	One	417:419	One	417:419	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	3	38	with	annotations	524:534	arg1	glycans					541:547	glycans	541:547	glycans	541:547	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	1	39	theme	glycosylation	304:316	arg1	sites					318:322	glycosylation sites	304:322	glycosylation sites	304:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	5	40	theme	standard	1019:1026	arg1	framework					1037:1045	a standard semantic framework	1017:1045	a standard semantic framework to describe and represent glycoproteomics data	1017:1092	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	5	40	theme	standard	1019:1026	arg1	Ontology					994:1001	the GlycoConjugate Ontology	975:1001	the GlycoConjugate Ontology (GlycoCoO)	975:1012	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	4	41	theme	site	803:806	arg1	information					808:818	partially missing site information	785:818	partially missing site information	785:818	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	1	42	from	increase	241:248	arg1	glycans					292:298	their attached glycans	277:298	their attached glycans	277:298	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	1	42	from	increase	241:248	arg1	sites					318:322	glycosylation sites	304:322	glycosylation sites	304:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	1	42	from	increase	241:248	arg1	proteins					267:274	the reporting proteins	253:274	the reporting proteins	253:274	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	5	43	theme	GlycoConjugate	979:992	arg1	GlycoCoO					1004:1011	GlycoCoO	1004:1011	GlycoCoO	1004:1011	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	5	43	theme	GlycoConjugate	979:992	arg1	Ontology					994:1001	the GlycoConjugate Ontology	975:1001	the GlycoConjugate Ontology (GlycoCoO)	975:1012	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	5	43	theme	GlycoConjugate	979:992	arg1	framework					1037:1045	a standard semantic framework	1017:1045	a standard semantic framework to describe and represent glycoproteomics data	1017:1092	To support the above, we have developed the GlycoConjugate Ontology (GlycoCoO) as a standard semantic framework to describe and represent glycoproteomics data.
33677548	4	44	theme	missing	795:801	arg1	information					808:818	partially missing site information	785:818	partially missing site information	785:818	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	3	45	theme	standard	468:475	arg1	reasons					434:440	the major reasons	424:440	the major reasons	424:440	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	3	45	theme	standard	468:475	arg1	absence					449:455	the absence	445:455	the absence of digital standard to represent glycoproteins and the challenging annotations with glycans	445:547	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	3	45	theme	standard	468:475	arg1	One					417:419	One	417:419	One	417:419	One of the major reasons is the absence of digital standard to represent glycoproteins and the challenging annotations with glycans.
33677548	4	46	theme	single	696:701	arg1	glycans					703:709	single glycans	696:709	single glycans	696:709	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	47	theme	glycosylation	755:767	arg1	deal					775:778	deal	775:778	deal with partially missing site information if no site mapping was performed	775:851	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	47	theme	glycosylation	755:767	arg1	side					769:772	a specific glycosylation side	744:772	a specific glycosylation side	744:772	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	1	48	gly	glycosylation	304:316	arg2	sites					318:322	glycosylation sites	304:322	glycosylation sites	304:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	4	49	gly	glycoforms	730:739	arg2	deal					775:778	deal	775:778	deal with partially missing site information if no site mapping was performed	775:851	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	4	49	gly	glycoforms	730:739	arg2	side					769:772	a specific glycosylation side	744:772	a specific glycosylation side	744:772	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	7	50	theme	database	1232:1239	arg1	providers					1241:1249	database providers	1232:1249	database providers	1232:1249	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	50	theme	database	1232:1239	arg1	documentation					1266:1278	supporting documentation	1255:1278	supporting documentation	1255:1278	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	50	theme	database	1232:1239	arg1	online					1294:1299	online	1294:1299	online	1294:1299	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	50	theme	database	1232:1239	arg1	ontology					1222:1229	The ontology	1218:1229	The ontology	1218:1229	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	51	dep	online	1294:1299	arg1	https					1302:1306	https	1302:1306	https://github.com/glycoinfo/GlycoCoO	1302:1338	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	7	51	dep	online	1294:1299	arg1	available					1284:1292	available	1284:1292	available	1284:1292	The ontology, database providers and supporting documentation are available online (https://github.com/glycoinfo/GlycoCoO).
33677548	2	52	theme	reports	357:363	arg1	few					344:346	few	344:346	few	344:346	However, only very few of these reports find their way into databases or data repositories.
33677548	1	53	theme	sustainable	229:239	arg1	increase					241:248	a sustainable increase	227:248	a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites	227:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33677548	4	54	theme	specific	920:927	arg1	site					929:932	a specific site	918:932	a specific site	918:932	Depending on the experimental method, such a standard must be able to represent glycans as complete structures or as compositions, store not just single glycans but also represent glycoforms on a specific glycosylation side, deal with partially missing site information if no site mapping was performed, and store abundances or ratios of glycans within a glycoform of a specific site.
33677548	1	55	theme	great	139:143	arg1	advances					145:152	great advances	139:152	great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites	139:322	Recent years have seen great advances in the development of glycoproteomics protocols and methods resulting in a sustainable increase in the reporting proteins, their attached glycans and glycosylation sites.
33554253	7	0	theme	3	1214:1214	arg1	structures					1235:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	10	1	theme	Fab	1733:1735	arg1	cleavage					1746:1753	an almost complete Fab fragment cleavage	1714:1753	an almost complete Fab fragment cleavage	1714:1753	Substitution of this threonine allowed an almost complete Fab fragment cleavage.
33554253	4	2	theme	SrtA	602:605	arg1	cleavage					607:614	SrtA cleavage	602:614	SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells	602:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	2	3	theme	non-natural	327:337	arg1	motif					368:372	the Sortase motif	356:372	the Sortase motif for site-directed labeling	356:399	Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling.
33554253	2	3	theme	non-natural	327:337	arg1	features					339:346	non-natural features	327:346	non-natural features such as the Sortase motif for site-directed labeling	327:399	Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling.
33554253	3	4	theme	cleavage	552:559	arg1	site					561:564	the cleavage site	548:564	the cleavage site close to the hinge region	548:590	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	4	5	theme	embryonic	672:680	arg1	HEK					690:692	HEK	690:692	HEK	690:692	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	4	5	theme	embryonic	672:680	arg1	kidney					682:687	human embryonic kidney	666:687	human embryonic kidney (HEK) 293 cells	666:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	1	6	theme	therapeutic	223:233	arg1	agents					235:240	therapeutic agents	223:240	therapeutic agents	223:240	Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years.
33554253	5	7	theme	O-glycans	845:853	arg1	presence					833:840	the presence	829:840	the presence of O-glycans close to the hinge region of the rRb-IgGs	829:895	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	8	8	theme	host	1443:1446	arg1	cell					1448:1451	the host cell	1439:1451	the host cell	1439:1451	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	8	9	theme	different	1271:1279	arg1	glycoforms					1290:1299	the different detected glycoforms	1267:1299	the different detected glycoforms	1267:1299	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	11	10	theme	SrtA	1829:1832	arg1	activity					1834:1841	the SrtA activity	1825:1841	the SrtA activity	1825:1841	Therefore, we could confirm the hypothesis that the O-glycans affect the SrtA activity, probably due to steric hindrance.
33554253	1	11	from	agents	235:240	arg1	years					273:277	recent years	266:277	recent years	266:277	Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years.
33554253	1	12	theme	Recombinant	149:159	arg1	immunoglobulins					161:175	Recombinant immunoglobulins	149:175	Recombinant immunoglobulins (rIgGs)	149:183	Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years.
33554253	1	12	theme	Recombinant	149:159	arg1	rIgGs					178:182	rIgGs	178:182	rIgGs	178:182	Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years.
33554253	5	13	contain	have	802:805	arg2	O-glycans					814:822	O-glycans	814:822	O-glycans	814:822	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	5	13	contain	have	802:805	arg2	N-					807:808	N-	807:808	N-	807:808	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	5	13	contain	have	802:805	arg1	Rb-IgGs					794:800	Nonrecombinant Rb-IgGs	779:800	Nonrecombinant Rb-IgGs	779:800	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	8	14	theme	glycoforms	1290:1299	arg1	distribution					1251:1262	The distribution	1247:1262	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis	1247:1332	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	8	15	with	agreement	1340:1348	arg1	studies					1364:1370	previous studies	1355:1370	previous studies on recombinant human IgG N-glycans	1355:1405	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	6	16	theme	rIgGs	1009:1013	arg1	pattern					998:1004	the glycosylation pattern	980:1004	the glycosylation pattern of rIgGs	980:1013	In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression.
33554253	2	17	theme	Genetic	280:286	arg1	engineering					288:298	Genetic engineering	280:298	Genetic engineering	280:298	Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling.
33554253	8	18	theme	N-glycan	1316:1323	arg1	analysis					1325:1332	our rRb-IgG N-glycan analysis	1304:1332	our rRb-IgG N-glycan analysis	1304:1332	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	7	19	theme	different	1191:1199	arg1	structures					1235:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	5	20	theme	rRb-IgGs	888:895	arg1	region					874:879	the hinge region	864:879	the hinge region of the rRb-IgGs	864:895	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	8	21	theme	produced	1498:1505	arg1	IgGs					1507:1510	the recombinant produced IgGs	1482:1510	the recombinant produced IgGs	1482:1510	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	4	22	theme	mouse	759:763	arg1	counterparts					765:776	their mouse counterparts	753:776	their mouse counterparts	753:776	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	0	23	theme	mass	113:116	arg1	analysis					139:146	comprehensive mass spectrometric glycan analysis	99:146	comprehensive mass spectrometric glycan analysis	99:146	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	0	24	theme	glycan	132:137	arg1	analysis					139:146	comprehensive mass spectrometric glycan analysis	99:146	comprehensive mass spectrometric glycan analysis	99:146	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	5	25	theme	Nonrecombinant	779:792	arg1	Rb-IgGs					794:800	Nonrecombinant Rb-IgGs	779:800	Nonrecombinant Rb-IgGs	779:800	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	9	26	theme	threonine	1554:1562	arg1	residue					1564:1570	the threonine residue	1550:1570	the threonine residue within the hinge region sequence XPTCPPPX	1550:1612	O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs.
33554253	3	27	theme	enzyme	421:426	arg1	SrtA					439:442	SrtA	439:442	SrtA	439:442	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	3	27	theme	enzyme	421:426	arg1	A					436:436	the enzyme Sortase A	417:436	the enzyme Sortase A (SrtA)	417:443	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	8	28	theme	previous	1355:1362	arg1	studies					1364:1370	previous studies	1355:1370	previous studies on recombinant human IgG N-glycans	1355:1405	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	10	29	theme	threonine	1696:1704	arg1	Substitution					1675:1686	Substitution	1675:1686	Substitution of this threonine	1675:1704	Substitution of this threonine allowed an almost complete Fab fragment cleavage.
33554253	0	30	theme	recombinant	17:27	arg1	immunoglobulins					36:50	recombinant rabbit immunoglobulins	17:50	recombinant rabbit immunoglobulins	17:50	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	9	31	theme	hinge	1583:1587	arg1	region					1589:1594	the hinge region sequence XPTCPPPX	1579:1612	the hinge region sequence XPTCPPPX	1579:1612	O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs.
33554253	7	32	theme	O-glycan	1226:1233	arg1	structures					1235:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	8	33	theme	human	1387:1391	arg1	N-glycans					1397:1405	recombinant human IgG N-glycans	1375:1405	recombinant human IgG N-glycans	1375:1405	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	3	34	theme	proteolytic	462:472	arg1	cleavage					474:481	the proteolytic cleavage	458:481	the proteolytic cleavage of rIgGs	458:490	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	0	35	theme	immunoglobulins	36:50	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation of recombinant rabbit immunoglobulins	0:50	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	7	36	theme	rRb-IgGs	1126:1133	arg1	O-glycans					1105:1113	O-glycans	1105:1113	O-glycans	1105:1113	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	7	36	theme	rRb-IgGs	1126:1133	arg1	N-					1098:1099	N-	1098:1099	N-	1098:1099	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	9	37	theme	sequence	1596:1603	arg1	XPTCPPPX					1605:1612	sequence XPTCPPPX	1596:1612	the hinge region sequence XPTCPPPX	1579:1612	O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs.
33554253	6	38	gly	glycosylation	984:996	arg1	rIgGs					1009:1013	rIgGs	1009:1013	rIgGs	1009:1013	In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression.
33554253	10	39	theme	complete	1724:1731	arg1	cleavage					1746:1753	an almost complete Fab fragment cleavage	1714:1753	an almost complete Fab fragment cleavage	1714:1753	Substitution of this threonine allowed an almost complete Fab fragment cleavage.
33554253	0	40	theme	protease	63:70	arg1	susceptibility					72:85	protease susceptibility	63:85	protease susceptibility	63:85	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	4	41	theme	engineered	619:628	arg1	rRb-IgGs					643:650	rRb-IgGs	643:650	rRb-IgGs	643:650	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	4	41	theme	engineered	619:628	arg1	IgGs					637:640	engineered rabbit IgGs	619:640	engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells	619:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	3	42	theme	Fab	522:524	arg1	fragments					526:534	their biotinylated Fab fragments	503:534	their biotinylated Fab fragments	503:534	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	8	43	from	studies	1364:1370	arg1	N-glycans					1397:1405	recombinant human IgG N-glycans	1375:1405	recombinant human IgG N-glycans	1375:1405	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	9	44	theme	nonrecombinant	1651:1664	arg1	Rb-IgGs					1666:1672	nonrecombinant Rb-IgGs	1651:1672	nonrecombinant Rb-IgGs	1651:1672	O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs.
33554253	7	45	theme	different	1216:1224	arg1	structures					1235:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	2	46	theme	features	339:346	arg1	introduction					311:322	the introduction	307:322	the introduction of non-natural features such as the Sortase motif for site-directed labeling	307:399	Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling.
33554253	3	47	theme	hinge	579:583	arg1	region					585:590	the hinge region	575:590	the hinge region	575:590	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	11	48	theme	steric	1860:1865	arg1	hindrance					1867:1875	steric hindrance	1860:1875	steric hindrance	1860:1875	Therefore, we could confirm the hypothesis that the O-glycans affect the SrtA activity, probably due to steric hindrance.
33554253	9	49	dep	region	1589:1594	arg1	XPTCPPPX					1605:1612	sequence XPTCPPPX	1596:1612	the hinge region sequence XPTCPPPX	1579:1612	O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs.
33554253	7	50	dep	analyzed	1085:1092	arg1	quantifying					1176:1186	quantifying	1176:1186	quantifying 13 different N-glycan and 3 different O-glycan structures	1176:1244	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	7	50	dep	analyzed	1085:1092	arg1	detecting					1162:1170	detecting	1162:1170	detecting	1162:1170	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	2	51	theme	Sortase	360:366	arg1	motif					368:372	the Sortase motif	356:372	the Sortase motif for site-directed labeling	356:399	Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling.
33554253	4	52	theme	human	666:670	arg1	HEK					690:692	HEK	690:692	HEK	690:692	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	4	52	theme	human	666:670	arg1	kidney					682:687	human embryonic kidney	666:687	human embryonic kidney (HEK) 293 cells	666:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	7	53	dep	N-	1098:1099	arg1	the					1094:1096	the	1094:1096	the	1094:1096	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	4	54	theme	IgGs	637:640	arg1	cleavage					607:614	SrtA cleavage	602:614	SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells	602:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	2	55	theme	site-directed	378:390	arg1	labeling					392:399	site-directed labeling	378:399	site-directed labeling	378:399	Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling.
33554253	5	56	theme	hinge	868:872	arg1	region					874:879	the hinge region	864:879	the hinge region of the rRb-IgGs	864:895	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	8	57	gly	glycosylation	1465:1477	arg1	IgGs					1507:1510	the recombinant produced IgGs	1482:1510	the recombinant produced IgGs	1482:1510	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	1	58	from	tools	257:261	arg1	years					273:277	recent years	266:277	recent years	266:277	Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years.
33554253	3	59	used	used	449:452	arg2	SrtA					439:442	SrtA	439:442	SrtA	439:442	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	3	59	used	used	449:452	arg2	A					436:436	the enzyme Sortase A	417:436	the enzyme Sortase A (SrtA)	417:443	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	8	60	theme	detected	1281:1288	arg1	glycoforms					1290:1299	the different detected glycoforms	1267:1299	the different detected glycoforms	1267:1299	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	7	61	theme	N-glycan	1201:1208	arg1	structures					1235:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	13 different N-glycan and 3 different O-glycan structures	1188:1244	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	8	62	from	distribution	1251:1262	arg1	analysis					1325:1332	our rRb-IgG N-glycan analysis	1304:1332	our rRb-IgG N-glycan analysis	1304:1332	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	8	63	theme	recombinant	1486:1496	arg1	IgGs					1507:1510	the recombinant produced IgGs	1482:1510	the recombinant produced IgGs	1482:1510	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	4	64	theme	kidney	682:687	arg1	cells					699:703	human embryonic kidney (HEK) 293 cells	666:703	human embryonic kidney (HEK) 293 cells	666:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	0	65	theme	comprehensive	99:111	arg1	analysis					139:146	comprehensive mass spectrometric glycan analysis	99:146	comprehensive mass spectrometric glycan analysis	99:146	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	6	66	theme	glycosylation	984:996	arg1	pattern					998:1004	the glycosylation pattern	980:1004	the glycosylation pattern of rIgGs	980:1013	In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression.
33554253	8	67	theme	IgGs	1507:1510	arg1	glycosylation					1465:1477	the glycosylation	1461:1477	the glycosylation of the recombinant produced IgGs	1461:1510	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	8	68	theme	rRb-IgG	1308:1314	arg1	analysis					1325:1332	our rRb-IgG N-glycan analysis	1304:1332	our rRb-IgG N-glycan analysis	1304:1332	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	0	69	theme	spectrometric	118:130	arg1	analysis					139:146	comprehensive mass spectrometric glycan analysis	99:146	comprehensive mass spectrometric glycan analysis	99:146	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	5	70	theme	SrtA	952:955	arg1	cleavage					957:964	SrtA cleavage	952:964	SrtA cleavage	952:964	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	7	71	theme	HEK293	1148:1153	arg1	cells					1155:1159	HEK293 cells	1148:1159	HEK293 cells	1148:1159	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	3	72	theme	Sortase	428:434	arg1	SrtA					439:442	SrtA	439:442	SrtA	439:442	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	3	72	theme	Sortase	428:434	arg1	A					436:436	the enzyme Sortase A	417:436	the enzyme Sortase A (SrtA)	417:443	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	4	73	theme	lower	726:730	arg1	yields					732:737	significantly lower yields	712:737	significantly lower yields	712:737	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	0	74	theme	rabbit	29:34	arg1	immunoglobulins					36:50	recombinant rabbit immunoglobulins	17:50	recombinant rabbit immunoglobulins	17:50	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	5	75	theme	antibodies	938:947	arg1	susceptibility					914:927	the susceptibility	910:927	the susceptibility of these antibodies to SrtA cleavage	910:964	Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage.
33554253	6	76	theme	host	1040:1043	arg1	cell					1045:1048	the host cell	1036:1048	the host cell used for expression	1036:1068	In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression.
33554253	4	77	attach	derived	653:659	arg2	IgGs					637:640	engineered rabbit IgGs	619:640	engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells	619:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	4	77	attach	derived	653:659	arg2	rRb-IgGs					643:650	rRb-IgGs	643:650	rRb-IgGs	643:650	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	4	77	attach	derived	653:659	arg1	cells					699:703	human embryonic kidney (HEK) 293 cells	666:703	human embryonic kidney (HEK) 293 cells	666:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	3	78	theme	rIgGs	486:490	arg1	cleavage					474:481	the proteolytic cleavage	458:481	the proteolytic cleavage of rIgGs	458:490	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	7	79	theme	various	1118:1124	arg1	rRb-IgGs					1126:1133	various rRb-IgGs	1118:1133	various rRb-IgGs expressed in HEK293 cells	1118:1159	Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures.
33554253	1	80	theme	diagnostic	246:255	arg1	tools					257:261	diagnostic tools	246:261	diagnostic tools	246:261	Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years.
33554253	0	81	gly	Glycosylation	0:12	arg1	immunoglobulins					36:50	recombinant rabbit immunoglobulins	17:50	recombinant rabbit immunoglobulins	17:50	Glycosylation of recombinant rabbit immunoglobulins influences protease susceptibility as shown by comprehensive mass spectrometric glycan analysis.
33554253	8	82	theme	recombinant	1375:1385	arg1	N-glycans					1397:1405	recombinant human IgG N-glycans	1375:1405	recombinant human IgG N-glycans	1375:1405	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	8	83	theme	IgG	1393:1395	arg1	N-glycans					1397:1405	recombinant human IgG N-glycans	1375:1405	recombinant human IgG N-glycans	1375:1405	The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs.
33554253	3	84	theme	biotinylated	509:520	arg1	fragments					526:534	their biotinylated Fab fragments	503:534	their biotinylated Fab fragments	503:534	In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region.
33554253	1	85	theme	recent	266:271	arg1	years					273:277	recent years	266:277	recent years	266:277	Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years.
33554253	10	86	theme	fragment	1737:1744	arg1	cleavage					1746:1753	an almost complete Fab fragment cleavage	1714:1753	an almost complete Fab fragment cleavage	1714:1753	Substitution of this threonine allowed an almost complete Fab fragment cleavage.
33554253	4	87	theme	rabbit	630:635	arg1	rRb-IgGs					643:650	rRb-IgGs	643:650	rRb-IgGs	643:650	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
33554253	4	87	theme	rabbit	630:635	arg1	IgGs					637:640	engineered rabbit IgGs	619:640	engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells	619:703	However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts.
34662441	7	0	theme	membrane-proximal	1473:1489	arg1	sites					1491:1495	membrane-proximal sites	1473:1495	membrane-proximal sites	1473:1495	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	8	1	theme	descriptive	1619:1629	arg1	analysis					1631:1638	initial descriptive analysis	1611:1638	initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue	1611:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	6	2	theme	glycoforms	1264:1273	arg1	presence					1239:1246	The presence	1235:1246	The presence of high mannose glycoforms at the former sequons	1235:1295	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	3	3	theme	site-specific	556:568	arg1	glycoforms					570:579	the site-specific glycoforms	552:579	the site-specific glycoforms of PSMA	552:587	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	5	4	theme	PSMA	1187:1190	arg1	domain					1192:1197	the exposed apical PSMA domain	1168:1197	the exposed apical PSMA domain	1168:1197	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	9	5	theme	glycoforms	1872:1881	arg1	glycoforms					1768:1777	PSMA glycoforms	1763:1777	PSMA glycoforms in the context of tumor staging	1763:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	5	theme	glycoforms	1872:1881	arg1	detection					1824:1832	noninvasive detection	1812:1832	noninvasive detection of prostate tumors	1812:1851	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	5	theme	glycoforms	1872:1881	arg1	impact					1862:1867	the impact	1858:1867	the impact of glycoforms	1858:1881	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	6	6	theme	high	1251:1254	arg1	glycoforms					1264:1273	high mannose glycoforms	1251:1273	high mannose glycoforms	1251:1273	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	1	7	theme	pathways	311:318	arg1	dysregulation					280:292	the dysregulation	276:292	the dysregulation of glycosylation pathways	276:318	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	1	8	theme	INTRODUCTION	98:109	arg1	modification					174:185	a ubiquitous and variable posttranslational modification	130:185	a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins	130:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	1	8	theme	INTRODUCTION	98:109	arg1	N-glycosylation					111:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	9	9	theme	physicochemical	1886:1900	arg1	characteristics					1916:1930	physicochemical and enzymatic characteristics	1886:1930	physicochemical and enzymatic characteristics of PSMA	1886:1938	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	10	theme	enzymatic	1906:1914	arg1	characteristics					1916:1930	physicochemical and enzymatic characteristics	1886:1930	physicochemical and enzymatic characteristics of PSMA	1886:1938	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	4	11	theme	recombinant	720:730	arg1	PSMA					732:735	recombinant PSMA	720:735	recombinant PSMA expressed in insect cells	720:761	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	3	12	from	distribution	536:547	arg1	insect					592:597	insect	592:597	insect	592:597	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	3	12	from	distribution	536:547	arg1	tissue					667:672	prostate tissue	658:672	prostate tissue	658:672	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	1	13	theme	physiological	202:214	arg1	functions					216:224	physiological functions	202:224	physiological functions of secretory and membrane-associated proteins	202:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	3	14	theme	embryonic	606:614	arg1	kidney					616:621	human embryonic kidney	600:621	human embryonic kidney	600:621	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	6	15	theme	complex	1411:1417	arg1	structures					1419:1428	the complex structures	1407:1428	the complex structures	1407:1428	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	9	16	theme	tissue-specific	1945:1959	arg1	manner					1961:1966	a tissue-specific manner	1943:1966	a tissue-specific manner	1943:1966	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	3	17	theme	prostate	628:635	arg1	cells					644:648	prostate cancer cells	628:648	prostate cancer cells	628:648	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	5	18	theme	spatial	946:952	arg1	distribution					954:965	an interesting spatial distribution	931:965	an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans	931:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	7	19	gly	glycosylation	1501:1513	arg1	line					1434:1437	line	1434:1437	line with the limited accessibility of membrane-proximal sites	1434:1495	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	7	19	gly	glycosylation	1501:1513	arg1	site					1539:1542	the N51 site	1531:1542	the N51 site positioned closest to the membrane	1531:1577	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	3	20	theme	prostate	658:665	arg1	tissue					667:672	prostate tissue	658:672	prostate tissue	658:672	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	9	21	gly	glycoforms	1768:1777	arg2	context					1786:1792	the context	1782:1792	the context of tumor staging	1782:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	21	gly	glycoforms	1768:1777	arg1	tumors					1846:1851	prostate tumors	1837:1851	prostate tumors	1837:1851	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	21	gly	glycoforms	1768:1777	arg1	PSMA					1763:1766	PSMA glycoforms	1763:1777	PSMA glycoforms in the context of tumor staging	1763:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	21	gly	glycoforms	1768:1777	arg1	glycoforms					1872:1881	glycoforms	1872:1881	glycoforms	1872:1881	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	6	22	theme	pathway	1369:1375	arg1	enzymes					1339:1345	enzymes	1339:1345	enzymes of the glycosynthetic pathway required for the synthesis of the complex structures	1339:1428	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	4	23	from	tissue	914:919	arg1	samples					885:891	samples	885:891	samples from human cells and tissue	885:919	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	4	24	theme	insect	750:755	arg1	cells					757:761	insect cells	750:761	insect cells	750:761	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	0	25	theme	human	65:69	arg1	cells					71:75	human cells	65:75	human cells	65:75	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	4	26	from	cells	904:908	arg1	samples					885:891	samples	885:891	samples from human cells and tissue	885:919	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	1	27	theme	posttranslational	156:172	arg1	modification					174:185	a ubiquitous and variable posttranslational modification	130:185	a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins	130:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	1	27	theme	posttranslational	156:172	arg1	N-glycosylation					111:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	9	28	theme	PSMA	1763:1766	arg1	glycoforms					1768:1777	PSMA glycoforms	1763:1777	PSMA glycoforms in the context of tumor staging	1763:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	0	29	from	Glycoforms	0:9	arg1	cells					71:75	human cells	65:75	human cells	65:75	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	0	29	from	Glycoforms	0:9	arg1	tissue					90:95	prostate tissue	81:95	prostate tissue	81:95	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	6	30	theme	enzymes	1339:1345	arg1	access					1329:1334	the limited access	1317:1334	the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures	1317:1428	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	5	31	theme	surface-high	997:1008	arg1	glycans					1018:1024	the PSMA surface-high mannose glycans	988:1024	the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans	988:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	3	32	theme	METHODS	486:492	arg1	spectrometry					499:510	METHODS Mass spectrometry	486:510	METHODS Mass spectrometry	486:510	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	5	33	from	distribution	954:965	arg1	glycans					1018:1024	the PSMA surface-high mannose glycans	988:1024	the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans	988:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	2	34	theme	established	423:433	arg1	biomarker					435:443	an established biomarker	420:443	an established biomarker for prostate cancer imaging and therapy	420:483	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	2	34	theme	established	423:433	arg1	antigen					402:408	Prostate-specific membrane antigen	375:408	Prostate-specific membrane antigen (PSMA)	375:415	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	6	35	theme	structures	1419:1428	arg1	synthesis					1394:1402	the synthesis	1390:1402	the synthesis of the complex structures	1390:1428	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	5	36	theme	located	1157:1163	arg1	sites					1150:1154	the N121, N195, and N336 sites	1125:1154	the N121, N195, and N336 sites	1125:1154	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	5	37	theme	glycoforms	974:983	arg1	distribution					954:965	an interesting spatial distribution	931:965	an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans	931:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	9	38	theme	tumor	1797:1801	arg1	staging					1803:1809	tumor staging	1797:1809	tumor staging	1797:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	4	39	theme	high	804:807	arg1	glycans					817:823	high mannose glycans	804:823	high mannose glycans	804:823	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	2	40	dep	cancer	458:463	arg1	imaging					465:471	imaging	465:471	imaging	465:471	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	0	41	theme	human	14:18	arg1	antigen					47:53	human prostate-specific membrane antigen	14:53	human prostate-specific membrane antigen (PSMA)	14:60	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	0	41	theme	human	14:18	arg1	PSMA					56:59	PSMA	56:59	PSMA	56:59	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	1	42	theme	ubiquitous	132:141	arg1	modification					174:185	a ubiquitous and variable posttranslational modification	130:185	a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins	130:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	1	42	theme	ubiquitous	132:141	arg1	N-glycosylation					111:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	4	43	theme	mannose	852:858	arg1	glycans					860:866	high mannose glycans	847:866	high mannose glycans	847:866	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	0	44	theme	membrane	38:45	arg1	antigen					47:53	human prostate-specific membrane antigen	14:53	human prostate-specific membrane antigen (PSMA)	14:60	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	0	44	theme	membrane	38:45	arg1	PSMA					56:59	PSMA	56:59	PSMA	56:59	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	1	45	theme	cancer	345:350	arg1	growth					352:357	cancer growth	345:357	cancer growth	345:357	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	5	46	gly	glycoforms	1044:1053	arg2	sequons					1083:1089	the N459, N476, and N638 sequons	1058:1089	the N459, N476, and N638 sequons facing the plasma membrane	1058:1116	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	8	47	located	observed	1666:1673	arg1	tissue					1705:1710	prostate tissue	1696:1710	prostate tissue	1696:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	8	47	located	observed	1666:1673	arg2	PSMA					1661:1664	PSMA	1661:1664	PSMA observed in cell lines and in prostate tissue	1661:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	8	47	located	observed	1666:1673	arg1	lines					1683:1687	cell lines	1678:1687	cell lines	1678:1687	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	9	48	theme	prostate	1837:1844	arg1	tumors					1846:1851	prostate tumors	1837:1851	prostate tumors	1837:1851	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	2	49	theme	Prostate-specific	375:391	arg1	biomarker					435:443	an established biomarker	420:443	an established biomarker for prostate cancer imaging and therapy	420:483	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	2	49	theme	Prostate-specific	375:391	arg1	PSMA					411:414	PSMA	411:414	PSMA	411:414	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	2	49	theme	Prostate-specific	375:391	arg1	antigen					402:408	Prostate-specific membrane antigen	375:408	Prostate-specific membrane antigen (PSMA)	375:415	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	7	50	with	line	1434:1437	arg1	accessibility					1456:1468	the limited accessibility	1444:1468	the limited accessibility of membrane-proximal sites	1444:1495	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	1	51	theme	membrane-associated	243:261	arg1	proteins					263:270	secretory and membrane-associated proteins	229:270	secretory and membrane-associated proteins	229:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	7	52	theme	sites	1491:1495	arg1	accessibility					1456:1468	the limited accessibility	1444:1468	the limited accessibility of membrane-proximal sites	1444:1495	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	3	53	theme	glycoforms	570:579	arg1	distribution					536:547	the distribution	532:547	the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue	532:672	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	5	54	theme	complex	1218:1224	arg1	glycans					1226:1232	complex glycans	1218:1232	complex glycans	1218:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	9	55	from	detection	1824:1832	arg1	context					1786:1792	the context	1782:1792	the context of tumor staging	1782:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	4	56	located	detected	873:880	arg1	samples					885:891	samples	885:891	samples from human cells and tissue	885:919	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	4	56	located	detected	873:880	arg2	complex					826:832	complex	826:832	complex	826:832	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	4	56	located	detected	873:880	arg2	RESULTS					706:712	RESULTS	706:712	RESULTS	706:712	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	4	56	located	detected	873:880	arg2	glycans					860:866	high mannose glycans	847:866	high mannose glycans	847:866	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	4	56	located	detected	873:880	arg2	hybrid					835:840	hybrid	835:840	hybrid	835:840	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	5	57	theme	apical	1180:1185	arg1	domain					1192:1197	the exposed apical PSMA domain	1168:1197	the exposed apical PSMA domain	1168:1197	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	7	58	theme	limited	1448:1454	arg1	accessibility					1456:1468	the limited accessibility	1444:1468	the limited accessibility of membrane-proximal sites	1444:1495	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	4	59	theme	human	898:902	arg1	cells					904:908	human cells	898:908	human cells	898:908	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	8	60	theme	initial	1611:1617	arg1	analysis					1631:1638	initial descriptive analysis	1611:1638	initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue	1611:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	6	61	theme	mannose	1256:1262	arg1	glycoforms					1264:1273	high mannose glycoforms	1251:1273	high mannose glycoforms	1251:1273	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	8	62	theme	cell	1678:1681	arg1	lines					1683:1687	cell lines	1678:1687	cell lines	1678:1687	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	1	63	theme	glycosylation	297:309	arg1	pathways					311:318	glycosylation pathways	297:318	glycosylation pathways	297:318	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	5	64	contain	carried	1200:1206	arg1	sites					1150:1154	the N121, N195, and N336 sites	1125:1154	the N121, N195, and N336 sites	1125:1154	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	5	64	contain	carried	1200:1206	arg2	glycans					1226:1232	complex glycans	1218:1232	complex glycans	1218:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	6	65	attach	presence	1239:1246	arg1	sequons					1289:1295	the former sequons	1278:1295	the former sequons	1278:1295	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	6	65	attach	presence	1239:1246	arg2	glycoforms					1264:1273	high mannose glycoforms	1251:1273	high mannose glycoforms	1251:1273	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	3	66	theme	PSMA	584:587	arg1	glycoforms					570:579	the site-specific glycoforms	552:579	the site-specific glycoforms of PSMA	552:587	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	9	67	from	impact	1862:1867	arg1	context					1786:1792	the context	1782:1792	the context of tumor staging	1782:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	8	68	theme	prostate	1696:1703	arg1	tissue					1705:1710	prostate tissue	1696:1710	prostate tissue	1696:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	9	69	from	research	1749:1756	arg1	characteristics					1916:1930	physicochemical and enzymatic characteristics	1886:1930	physicochemical and enzymatic characteristics of PSMA	1886:1938	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	5	70	from	domain	1192:1197	arg1	located					1157:1163	located	1157:1163	located	1157:1163	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	3	71	theme	human	600:604	arg1	kidney					616:621	human embryonic kidney	600:621	human embryonic kidney	600:621	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	9	72	theme	PSMA	1935:1938	arg1	characteristics					1916:1930	physicochemical and enzymatic characteristics	1886:1930	physicochemical and enzymatic characteristics of PSMA	1886:1938	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	3	73	theme	cancer	637:642	arg1	cells					644:648	prostate cancer cells	628:648	prostate cancer cells	628:648	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	7	74	located	observed	1519:1526	arg2	glycosylation					1501:1513	no glycosylation	1498:1513	no glycosylation	1498:1513	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	7	74	located	observed	1519:1526	arg1	line					1434:1437	line	1434:1437	line with the limited accessibility of membrane-proximal sites	1434:1495	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	7	74	located	observed	1519:1526	arg1	site					1539:1542	the N51 site	1531:1542	the N51 site positioned closest to the membrane	1531:1577	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	5	75	theme	plasma	1102:1107	arg1	membrane					1109:1116	the plasma membrane	1098:1116	the plasma membrane	1098:1116	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	5	76	theme	interesting	934:944	arg1	distribution					954:965	an interesting spatial distribution	931:965	an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans	931:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	8	77	gly	glycoforms	1647:1656	arg1	PSMA					1661:1664	PSMA	1661:1664	PSMA observed in cell lines and in prostate tissue	1661:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	6	78	theme	limited	1321:1327	arg1	access					1329:1334	the limited access	1317:1334	the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures	1317:1428	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	6	79	theme	former	1282:1287	arg1	sequons					1289:1295	the former sequons	1278:1295	the former sequons	1278:1295	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	6	80	gly	glycoforms	1264:1273	arg1	mannose					1256:1262	high mannose glycoforms	1251:1273	high mannose glycoforms	1251:1273	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	9	81	theme	further	1741:1747	arg1	research					1749:1756	further research	1741:1756	further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA	1741:1938	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	6	82	theme	glycosynthetic	1354:1367	arg1	pathway					1369:1375	the glycosynthetic pathway	1350:1375	the glycosynthetic pathway required for the synthesis of the complex structures	1350:1428	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	1	83	theme	variable	147:154	arg1	modification					174:185	a ubiquitous and variable posttranslational modification	130:185	a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins	130:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	1	83	theme	variable	147:154	arg1	N-glycosylation					111:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation	98:125	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	0	84	theme	prostate	81:88	arg1	tissue					90:95	prostate tissue	81:95	prostate tissue	81:95	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	5	85	theme	PSMA	992:995	arg1	glycans					1018:1024	the PSMA surface-high mannose glycans	988:1024	the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans	988:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	7	86	theme	N51	1535:1537	arg1	site					1539:1542	the N51 site	1531:1542	the N51 site positioned closest to the membrane	1531:1577	In line with the limited accessibility of membrane-proximal sites, no glycosylation was observed at the N51 site positioned closest to the membrane.
34662441	3	87	gly	glycoforms	570:579	arg1	PSMA					584:587	PSMA	584:587	PSMA	584:587	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	4	88	theme	mannose	809:815	arg1	glycans					817:823	high mannose glycans	804:823	high mannose glycans	804:823	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	5	89	from	sequons	1083:1089	arg1	glycoforms					1044:1053	the dominant glycoforms	1031:1053	the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane	1031:1116	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	5	90	theme	mannose	1010:1016	arg1	glycans					1018:1024	the PSMA surface-high mannose glycans	988:1024	the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans	988:1232	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	3	91	theme	Mass	494:497	arg1	spectrometry					499:510	METHODS Mass spectrometry	486:510	METHODS Mass spectrometry	486:510	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	8	92	dep	CONCLUSIONS	1580:1590	arg1	presents					1602:1609	presents	1602:1609	presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue	1602:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	0	93	theme	prostate-specific	20:36	arg1	antigen					47:53	human prostate-specific membrane antigen	14:53	human prostate-specific membrane antigen (PSMA)	14:60	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	0	93	theme	prostate-specific	20:36	arg1	PSMA					56:59	PSMA	56:59	PSMA	56:59	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	9	94	theme	staging	1803:1809	arg1	context					1786:1792	the context	1782:1792	the context of tumor staging	1782:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	3	95	theme	immunoaffinity	679:692	arg1	enrichment					694:703	immunoaffinity enrichment	679:703	immunoaffinity enrichment	679:703	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	3	96	used	used	516:519	arg2	spectrometry					499:510	METHODS Mass spectrometry	486:510	METHODS Mass spectrometry	486:510	METHODS Mass spectrometry was used to analyze the distribution of the site-specific glycoforms of PSMA in insect, human embryonic kidney, and prostate cancer cells, and in prostate tissue upon immunoaffinity enrichment.
34662441	0	97	theme	antigen	47:53	arg1	Glycoforms					0:9	Glycoforms	0:9	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue	0:95	Glycoforms of human prostate-specific membrane antigen (PSMA) in human cells and prostate tissue.
34662441	5	98	theme	exposed	1172:1178	arg1	domain					1192:1197	the exposed apical PSMA domain	1168:1197	the exposed apical PSMA domain	1168:1197	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34662441	1	99	theme	secretory	229:237	arg1	proteins					263:270	secretory and membrane-associated proteins	229:270	secretory and membrane-associated proteins	229:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	9	100	theme	noninvasive	1812:1822	arg1	detection					1824:1832	noninvasive detection	1812:1832	noninvasive detection of prostate tumors	1812:1851	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	4	101	theme	high	847:850	arg1	glycans					860:866	high mannose glycans	847:866	high mannose glycans	847:866	RESULTS While recombinant PSMA expressed in insect cells was decorated mainly by paucimannose and high mannose glycans, complex, hybrid, and high mannose glycans were detected in samples from human cells and tissue.
34662441	2	102	theme	prostate	449:456	arg1	cancer					458:463	prostate cancer imaging and therapy	449:483	cancer	458:463	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	9	103	from	glycoforms	1768:1777	arg1	context					1786:1792	the context	1782:1792	the context of tumor staging	1782:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	2	104	theme	membrane	393:400	arg1	biomarker					435:443	an established biomarker	420:443	an established biomarker for prostate cancer imaging and therapy	420:483	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	2	104	theme	membrane	393:400	arg1	PSMA					411:414	PSMA	411:414	PSMA	411:414	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	2	104	theme	membrane	393:400	arg1	antigen					402:408	Prostate-specific membrane antigen	375:408	Prostate-specific membrane antigen (PSMA)	375:415	Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer imaging and therapy.
34662441	8	105	theme	glycoforms	1647:1656	arg1	analysis					1631:1638	initial descriptive analysis	1611:1638	initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue	1611:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	6	106	from	sequons	1289:1295	arg1	presence					1239:1246	The presence	1235:1246	The presence of high mannose glycoforms at the former sequons	1235:1295	The presence of high mannose glycoforms at the former sequons likely results from the limited access of enzymes of the glycosynthetic pathway required for the synthesis of the complex structures.
34662441	9	107	theme	tumors	1846:1851	arg1	glycoforms					1768:1777	PSMA glycoforms	1763:1777	PSMA glycoforms in the context of tumor staging	1763:1809	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	107	theme	tumors	1846:1851	arg1	detection					1824:1832	noninvasive detection	1812:1832	noninvasive detection of prostate tumors	1812:1851	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	9	107	theme	tumors	1846:1851	arg1	impact					1862:1867	the impact	1858:1867	the impact of glycoforms	1858:1881	It will hopefully stimulate further research into PSMA glycoforms in the context of tumor staging, noninvasive detection of prostate tumors, and the impact of glycoforms on physicochemical and enzymatic characteristics of PSMA in a tissue-specific manner.
34662441	8	108	theme	PSMA	1661:1664	arg1	glycoforms					1647:1656	the glycoforms	1643:1656	the glycoforms of PSMA observed in cell lines and in prostate tissue	1643:1710	CONCLUSIONS Our study presents initial descriptive analysis of the glycoforms of PSMA observed in cell lines and in prostate tissue.
34662441	1	109	theme	proteins	263:270	arg1	functions					216:224	physiological functions	202:224	physiological functions of secretory and membrane-associated proteins	202:270	INTRODUCTION N-glycosylation is a ubiquitous and variable posttranslational modification that regulates physiological functions of secretory and membrane-associated proteins and the dysregulation of glycosylation pathways is often associated with cancer growth and metastasis.
34662441	5	110	theme	dominant	1035:1042	arg1	glycoforms					1044:1053	the dominant glycoforms	1031:1053	the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane	1031:1116	We noted an interesting spatial distribution of the glycoforms on the PSMA surface-high mannose glycans were the dominant glycoforms at the N459, N476, and N638 sequons facing the plasma membrane, while the N121, N195, and N336 sites, located at the exposed apical PSMA domain, carried primarily complex glycans.
34723506	8	0	theme	approach	1166:1173	arg1	Application					1146:1156	Application	1146:1156	Application of this approach to animal and human brain N-glycans	1146:1209	Application of this approach to animal and human brain N-glycans immediately identified the majority of structures as being of the bisected type.
34723506	10	1	theme	missing	1554:1560	arg1	pieces					1562:1567	the still missing pieces	1544:1567	the still missing pieces of the N-glycome in our most noble organ	1544:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	3	2	theme	spectrometric	668:680	arg1	detection					682:690	mass spectrometric detection	663:690	mass spectrometric detection	663:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	2	3	theme	unambiguous	339:349	arg1	identification					351:364	unambiguous identification	339:364	unambiguous identification of isomeric structures	339:387	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	8	4	theme	animal	1178:1183	arg1	N-glycans					1201:1209	animal and human brain N-glycans	1178:1209	animal and human brain N-glycans	1178:1209	Application of this approach to animal and human brain N-glycans immediately identified the majority of structures as being of the bisected type.
34723506	7	5	theme	standard	1123:1130	arg1	chromatogram					1132:1143	a standard chromatogram	1121:1143	a standard chromatogram	1121:1143	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	10	6	theme	glycomics	1764:1772	arg1	development					1717:1727	the overdue development	1705:1727	the overdue development of isomer-specific deep structural glycomics	1705:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	8	7	theme	human	1189:1193	arg1	N-glycans					1201:1209	animal and human brain N-glycans	1178:1209	animal and human brain N-glycans	1178:1209	Application of this approach to animal and human brain N-glycans immediately identified the majority of structures as being of the bisected type.
34723506	2	8	from	art	332:334	arg1	mixtures					400:407	complex mixtures	392:407	complex mixtures	392:407	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	10	9	theme	N-glycome	1576:1584	arg1	pieces					1562:1567	the still missing pieces	1544:1567	the still missing pieces of the N-glycome in our most noble organ	1544:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	5	10	theme	biosynthetized	852:865	arg1	isomers					867:873	the 40 biosynthetized isomers	845:873	the 40 biosynthetized isomers	845:873	Nearly all of the 40 biosynthetized isomers occupied unique elution positions.
34723506	6	11	theme	carbon	985:990	arg1	selectivity					953:963	the unique isomer selectivity	935:963	the unique isomer selectivity of porous graphitic carbon	935:990	This result demonstrates the unique isomer selectivity of porous graphitic carbon.
34723506	10	12	theme	noble	1598:1602	arg1	organ					1604:1608	our most noble organ	1589:1608	our most noble organ	1589:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	7	13	theme	retention	1086:1094	arg1	times					1096:1100	standard retention times	1077:1100	standard retention times	1077:1100	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	10	14	theme	structural	1753:1762	arg1	glycomics					1764:1772	isomer-specific deep structural glycomics	1732:1772	isomer-specific deep structural glycomics	1732:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	6	15	theme	porous	968:973	arg1	carbon					985:990	porous graphitic carbon	968:990	porous graphitic carbon	968:990	This result demonstrates the unique isomer selectivity of porous graphitic carbon.
34723506	8	16	theme	structures	1250:1259	arg1	majority					1238:1245	the majority	1234:1245	the majority of structures	1234:1259	Application of this approach to animal and human brain N-glycans immediately identified the majority of structures as being of the bisected type.
34723506	10	17	theme	itself─in	1623:1631	arg1	conjunction					1633:1643	itself─in conjunction	1623:1643	itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics	1623:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	7	18	theme	internal	1058:1065	arg1	N-glycan					1067:1074	isotope-labeled internal N-glycan	1042:1074	isotope-labeled internal N-glycan	1042:1074	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	6	19	theme	unique	939:944	arg1	selectivity					953:963	the unique isomer selectivity	935:963	the unique isomer selectivity of porous graphitic carbon	935:990	This result demonstrates the unique isomer selectivity of porous graphitic carbon.
34723506	3	20	theme	time	602:605	arg1	library					607:613	a deci-minute accurate retention time library	569:613	a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection	569:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	1	21	theme	glycosylation	123:135	arg1	importance					101:110	The importance	97:110	The importance of protein glycosylation in the biomedical field	97:159	The importance of protein glycosylation in the biomedical field requires methods that not only quantitate structures by their monosaccharide composition, but also resolve and identify the many isomers expressed by mammalian cells.
34723506	2	22	theme	high-throughput	473:487	arg1	glycomics					489:497	high-throughput glycomics	473:497	high-throughput glycomics	473:497	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	0	23	theme	Brain	52:56	arg1	N-Glycans					33:41	Hybrid-Type N-Glycans	21:41	Hybrid-Type N-Glycans of Human Brain	21:56	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	3	24	theme	accurate	583:590	arg1	library					607:613	a deci-minute accurate retention time library	569:613	a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection	569:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	5	25	theme	elution	891:897	arg1	positions					899:907	unique elution positions	884:907	unique elution positions	884:907	Nearly all of the 40 biosynthetized isomers occupied unique elution positions.
34723506	2	26	theme	advance	462:468	arg1	pace					454:457	the fast pace	445:457	the fast pace of advance of high-throughput glycomics	445:497	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	0	27	from	X	16:16	arg1	N-Glycans					33:41	Hybrid-Type N-Glycans	21:41	Hybrid-Type N-Glycans of Human Brain	21:56	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	0	28	theme	Structural	75:84	arg1	Glycomics					86:94	Deep Structural Glycomics	70:94	Deep Structural Glycomics	70:94	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	9	29	theme	hybrid-type	1317:1327	arg1	glycans					1329:1335	hybrid-type glycans	1317:1335	hybrid-type glycans	1317:1335	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	10	30	theme	grid	1486:1489	arg1	approach					1491:1498	the time grid approach	1477:1498	the time grid approach implemented herein	1477:1517	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	10	31	theme	starting	1686:1693	arg1	point					1695:1699	a starting point	1684:1699	a starting point for the overdue development of isomer-specific deep structural glycomics	1684:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	4	32	theme	fundamental	728:738	arg1	type					749:752	the fundamental N-glycan type	724:752	the fundamental N-glycan type consisting of five hexoses, four N-acetylhexosamines and one fucose residue	724:828	We implemented the concept for the fundamental N-glycan type consisting of five hexoses, four N-acetylhexosamines and one fucose residue.
34723506	0	33	theme	Bisecting	0:8	arg1	X					16:16	Bisecting Lewis X	0:16	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain	0:56	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	1	34	from	importance	101:110	arg1	field					155:159	the biomedical field	140:159	the biomedical field	140:159	The importance of protein glycosylation in the biomedical field requires methods that not only quantitate structures by their monosaccharide composition, but also resolve and identify the many isomers expressed by mammalian cells.
34723506	7	35	dep	the	998:1000	arg1	help					1002:1005	help	1002:1005	help	1002:1005	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	10	36	theme	overdue	1709:1715	arg1	development					1717:1727	the overdue development	1705:1727	the overdue development of isomer-specific deep structural glycomics	1705:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	1	37	theme	many	285:288	arg1	isomers					290:296	the many isomers	281:296	the many isomers expressed by mammalian cells	281:325	The importance of protein glycosylation in the biomedical field requires methods that not only quantitate structures by their monosaccharide composition, but also resolve and identify the many isomers expressed by mammalian cells.
34723506	10	38	from	pieces	1562:1567	arg1	organ					1604:1608	our most noble organ	1589:1608	our most noble organ	1589:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	3	39	theme	graphitic	626:634	arg1	chromatography					643:656	porous graphitic carbon chromatography	619:656	porous graphitic carbon chromatography with mass spectrometric detection	619:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	4	40	theme	fucose	815:820	arg1	residue					822:828	one fucose residue	811:828	one fucose residue	811:828	We implemented the concept for the fundamental N-glycan type consisting of five hexoses, four N-acetylhexosamines and one fucose residue.
34723506	9	41	theme	natural	1455:1461	arg1	source					1463:1468	a natural source	1453:1468	a natural source	1453:1468	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	0	42	theme	Hybrid-Type	21:31	arg1	N-Glycans					33:41	Hybrid-Type N-Glycans	21:41	Hybrid-Type N-Glycans of Human Brain	21:56	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	10	43	theme	deep	1748:1751	arg1	glycomics					1764:1772	isomer-specific deep structural glycomics	1732:1772	isomer-specific deep structural glycomics	1732:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	1	44	theme	mammalian	311:319	arg1	cells					321:325	mammalian cells	311:325	mammalian cells	311:325	The importance of protein glycosylation in the biomedical field requires methods that not only quantitate structures by their monosaccharide composition, but also resolve and identify the many isomers expressed by mammalian cells.
34723506	3	45	theme	mass	663:666	arg1	detection					682:690	mass spectrometric detection	663:690	mass spectrometric detection	663:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	10	46	with	conjunction	1633:1643	arg1	collision					1650:1658	collision	1650:1658	collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics	1650:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	2	47	theme	isomeric	369:376	arg1	structures					378:387	isomeric structures	369:387	isomeric structures	369:387	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	10	48	from	organ	1604:1608	arg1	pieces					1562:1567	the still missing pieces	1544:1567	the still missing pieces of the N-glycome in our most noble organ	1544:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	10	49	theme	pieces	1562:1567	arg1	discovery					1531:1539	discovery	1531:1539	discovery of the still missing pieces of the N-glycome in our most noble organ	1531:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	9	50	contain	containing	1374:1383	arg2	N-acetylglucosamine					1394:1412	bisected N-acetylglucosamine	1385:1412	bisected N-acetylglucosamine	1385:1412	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	9	50	contain	containing	1374:1383	arg1	X					1372:1372	galactosylated and even Lewis X	1342:1372	galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source	1342:1468	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	2	51	theme	identification	351:364	arg1	art					332:334	The art	328:334	The art of unambiguous identification of isomeric structures in complex mixtures	328:407	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	10	52	theme	most	1593:1596	arg1	organ					1604:1608	our most noble organ	1589:1608	our most noble organ	1589:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	3	53	with	chromatography	643:656	arg1	detection					682:690	mass spectrometric detection	663:690	mass spectrometric detection	663:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	3	54	dep	the	557:559	arg1	help					561:564	help	561:564	help	561:564	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	5	55	used	occupied	875:882	arg2	isomers					867:873	the 40 biosynthetized isomers	845:873	the 40 biosynthetized isomers	845:873	Nearly all of the 40 biosynthetized isomers occupied unique elution positions.
34723506	5	55	used	occupied	875:882	arg2	all					838:840	all	838:840	all	838:840	Nearly all of the 40 biosynthetized isomers occupied unique elution positions.
34723506	8	56	theme	brain	1195:1199	arg1	N-glycans					1201:1209	animal and human brain N-glycans	1178:1209	animal and human brain N-glycans	1178:1209	Application of this approach to animal and human brain N-glycans immediately identified the majority of structures as being of the bisected type.
34723506	7	57	theme	standard	1077:1084	arg1	times					1096:1100	standard retention times	1077:1100	standard retention times	1077:1100	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	6	58	theme	graphitic	975:983	arg1	carbon					985:990	porous graphitic carbon	968:990	porous graphitic carbon	968:990	This result demonstrates the unique isomer selectivity of porous graphitic carbon.
34723506	8	59	theme	bisected	1277:1284	arg1	type					1286:1289	the bisected type	1273:1289	the bisected type	1273:1289	Application of this approach to animal and human brain N-glycans immediately identified the majority of structures as being of the bisected type.
34723506	7	60	theme	N-glycan	1067:1074	arg1	grid					1034:1037	a rather tightly spaced grid	1010:1037	a rather tightly spaced grid of isotope-labeled internal N-glycan	1010:1074	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	7	61	theme	isotope-labeled	1042:1056	arg1	N-glycan					1067:1074	isotope-labeled internal N-glycan	1042:1074	isotope-labeled internal N-glycan	1042:1074	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	7	62	theme	spaced	1027:1032	arg1	grid					1034:1037	a rather tightly spaced grid	1010:1037	a rather tightly spaced grid of isotope-labeled internal N-glycan	1010:1074	With the help of a rather tightly spaced grid of isotope-labeled internal N-glycan, standard retention times were transposed to a standard chromatogram.
34723506	6	63	theme	isomer	946:951	arg1	selectivity					953:963	the unique isomer selectivity	935:963	the unique isomer selectivity of porous graphitic carbon	935:990	This result demonstrates the unique isomer selectivity of porous graphitic carbon.
34723506	3	64	theme	retention	592:600	arg1	library					607:613	a deci-minute accurate retention time library	569:613	a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection	569:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	1	65	theme	protein	115:121	arg1	glycosylation					123:135	protein glycosylation	115:135	protein glycosylation	115:135	The importance of protein glycosylation in the biomedical field requires methods that not only quantitate structures by their monosaccharide composition, but also resolve and identify the many isomers expressed by mammalian cells.
34723506	3	66	theme	deci-minute	571:581	arg1	library					607:613	a deci-minute accurate retention time library	569:613	a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection	569:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	5	67	theme	unique	884:889	arg1	positions					899:907	unique elution positions	884:907	unique elution positions	884:907	Nearly all of the 40 biosynthetized isomers occupied unique elution positions.
34723506	0	68	theme	Deep	70:73	arg1	Glycomics					86:94	Deep Structural Glycomics	70:94	Deep Structural Glycomics	70:94	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	1	69	theme	biomedical	144:153	arg1	field					155:159	the biomedical field	140:159	the biomedical field	140:159	The importance of protein glycosylation in the biomedical field requires methods that not only quantitate structures by their monosaccharide composition, but also resolve and identify the many isomers expressed by mammalian cells.
34723506	10	70	theme	time	1481:1484	arg1	approach					1491:1498	the time grid approach	1477:1498	the time grid approach implemented herein	1477:1517	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	2	71	theme	complex	392:398	arg1	mixtures					400:407	complex mixtures	392:407	complex mixtures	392:407	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	0	72	theme	Lewis	10:14	arg1	X					16:16	Bisecting Lewis X	0:16	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain	0:56	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	9	73	theme	galactosylated	1342:1355	arg1	X					1372:1372	galactosylated and even Lewis X	1342:1372	galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source	1342:1468	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	2	74	theme	structures	378:387	arg1	identification					351:364	unambiguous identification	339:364	unambiguous identification of isomeric structures	339:387	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	3	75	with	structures	541:550	arg1	the					557:559	the	557:559	the	557:559	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	9	76	theme	even	1361:1364	arg1	X					1372:1372	galactosylated and even Lewis X	1342:1372	galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source	1342:1468	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	3	77	theme	porous	619:624	arg1	chromatography					643:656	porous graphitic carbon chromatography	619:656	porous graphitic carbon chromatography with mass spectrometric detection	619:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	4	78	theme	N-glycan	740:747	arg1	type					749:752	the fundamental N-glycan type	724:752	the fundamental N-glycan type consisting of five hexoses, four N-acetylhexosamines and one fucose residue	724:828	We implemented the concept for the fundamental N-glycan type consisting of five hexoses, four N-acetylhexosamines and one fucose residue.
34723506	9	79	theme	Lewis	1366:1370	arg1	X					1372:1372	galactosylated and even Lewis X	1342:1372	galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source	1342:1468	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	2	80	theme	fast	449:452	arg1	pace					454:457	the fast pace	445:457	the fast pace of advance of high-throughput glycomics	445:497	The art of unambiguous identification of isomeric structures in complex mixtures, however, did not yet catch up with the fast pace of advance of high-throughput glycomics.
34723506	0	81	theme	Human	46:50	arg1	Brain					52:56	Human Brain	46:56	Human Brain	46:56	Bisecting Lewis X in Hybrid-Type N-Glycans of Human Brain Revealed by Deep Structural Glycomics.
34723506	9	82	theme	bisected	1385:1392	arg1	N-acetylglucosamine					1394:1412	bisected N-acetylglucosamine	1385:1412	bisected N-acetylglucosamine	1385:1412	Most notably, it exposed hybrid-type glycans with galactosylated and even Lewis X containing bisected N-acetylglucosamine, which have not yet been discovered in a natural source.
34723506	10	83	theme	isomer-specific	1732:1746	arg1	glycomics					1764:1772	isomer-specific deep structural glycomics	1732:1772	isomer-specific deep structural glycomics	1732:1772	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	10	84	from	N-glycome	1576:1584	arg1	organ					1604:1608	our most noble organ	1589:1608	our most noble organ	1589:1608	Thus, the time grid approach implemented herein facilitated discovery of the still missing pieces of the N-glycome in our most noble organ and suggests itself─in conjunction with collision induced dissociation─as a starting point for the overdue development of isomer-specific deep structural glycomics.
34723506	3	85	theme	carbon	636:641	arg1	chromatography					643:656	porous graphitic carbon chromatography	619:656	porous graphitic carbon chromatography with mass spectrometric detection	619:690	Here, we present a strategy for deducing structures with the help of a deci-minute accurate retention time library for porous graphitic carbon chromatography with mass spectrometric detection.
34723506	1	86	theme	monosaccharide	223:236	arg1	composition					238:248	their monosaccharide composition	217:248	their monosaccharide composition	217:248	The importance of protein glycosylation in the biomedical field requires methods that not only quantitate structures by their monosaccharide composition, but also resolve and identify the many isomers expressed by mammalian cells.
32325029	1	0	theme	complex	207:213	arg1	machineries					228:238	the complex biosynthetic machineries	203:238	the complex biosynthetic machineries of living cells	203:254	Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells.
32325029	6	1	theme	gain-of-chemical-functionality	997:1026	arg1	modification					1028:1039	a gain-of-chemical-functionality modification	995:1039	a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes	995:1218	This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
32325029	3	2	theme	fine	611:614	arg1	structure					616:624	glycan fine structure	604:624	glycan fine structure	604:624	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	2	3	theme	biosynthetic	401:412	arg1	regulation					414:423	disease-relevant biosynthetic regulation	384:423	disease-relevant biosynthetic regulation	384:423	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	6	4	theme	glycosyltransferases	1084:1103	arg1	products					1061:1068	the products	1057:1068	the products of individual glycosyltransferases	1057:1103	This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
32325029	2	5	theme	underlying	360:369	arg1	protein					371:377	underlying protein	360:377	underlying protein	360:377	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	3	6	theme	glycan	604:609	arg1	structure					616:624	glycan fine structure	604:624	glycan fine structure	604:624	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	6	7	theme	physiological	1196:1208	arg1	processes					1210:1218	major physiological processes	1190:1218	major physiological processes	1190:1218	This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
32325029	6	8	theme	individual	1073:1082	arg1	glycosyltransferases					1084:1103	individual glycosyltransferases	1073:1103	individual glycosyltransferases	1073:1103	This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
32325029	3	9	theme	chemical	507:514	arg1	functionalities					516:530	editable chemical functionalities	498:530	editable chemical functionalities	498:530	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	5	10	theme	disease-relevant	869:884	arg1	transferases					959:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	5	10	theme	disease-relevant	869:884	arg1	family					912:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	6	11	theme	glycan	1167:1172	arg1	contribution					1174:1185	glycan contribution	1167:1185	glycan contribution to major physiological processes	1167:1218	This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
32325029	6	12	from	modification	1028:1039	arg1	cells					1044:1048	cells	1044:1048	cells	1044:1048	This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
32325029	6	13	theme	major	1190:1194	arg1	processes					1210:1218	major physiological processes	1190:1218	major physiological processes	1190:1218	This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.
32325029	1	14	theme	posttranslational	107:123	arg1	modifications					125:137	posttranslational modifications	107:137	posttranslational modifications	107:137	Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells.
32325029	1	15	theme	living	243:248	arg1	cells					250:254	living cells	243:254	living cells	243:254	Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells.
32325029	0	16	theme	Bump-and-Hole	0:12	arg1	Engineering					14:24	Bump-and-Hole Engineering	0:24	Bump-and-Hole Engineering	0:24	Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells.
32325029	4	17	theme	biosynthetic	664:675	arg1	pathway					677:683	a non-natural substrate biosynthetic pathway	640:683	a non-natural substrate biosynthetic pathway	640:683	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	2	18	theme	disease-relevant	384:399	arg1	regulation					414:423	disease-relevant biosynthetic regulation	384:423	disease-relevant biosynthetic regulation	384:423	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	1	19	theme	cells	250:254	arg1	machineries					228:238	the complex biosynthetic machineries	203:238	the complex biosynthetic machineries of living cells	203:254	Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells.
32325029	0	20	theme	Specific	37:44	arg1	Substrates					46:55	Specific Substrates	37:55	Specific Substrates of Glycosyltransferases	37:79	Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells.
32325029	4	21	theme	substrate	654:662	arg1	pathway					677:683	a non-natural substrate biosynthetic pathway	640:683	a non-natural substrate biosynthetic pathway	640:683	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	5	22	theme	N-acetylgalactosaminyl	936:957	arg1	transferases					959:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	5	22	theme	N-acetylgalactosaminyl	936:957	arg1	family					912:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	3	23	theme	living	465:470	arg1	cells					472:476	living cells	465:476	living cells	465:476	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	1	24	theme	biosynthetic	215:226	arg1	machineries					228:238	the complex biosynthetic machineries	203:238	the complex biosynthetic machineries of living cells	203:254	Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells.
32325029	4	25	theme	living	802:807	arg1	cell					809:812	the living cell	798:812	the living cell	798:812	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	4	26	theme	surface	779:785	arg1	glycome					787:793	the cell surface glycome	770:793	the cell surface glycome of the living cell	770:812	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	3	27	with	glycans	485:491	arg1	functionalities					516:530	editable chemical functionalities	498:530	editable chemical functionalities	498:530	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	3	28	theme	editable	498:505	arg1	functionalities					516:530	editable chemical functionalities	498:530	editable chemical functionalities	498:530	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	5	29	theme	polypeptide	924:934	arg1	transferases					959:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	5	29	theme	polypeptide	924:934	arg1	family					912:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	5	30	theme	redundant	855:863	arg1	transferases					959:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	5	30	theme	redundant	855:863	arg1	family					912:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	2	31	theme	biological	304:313	arg1	processes					315:323	essential biological processes	294:323	essential biological processes	294:323	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	3	32	from	information	548:558	arg1	structure					616:624	glycan fine structure	604:624	glycan fine structure	604:624	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	3	32	from	information	548:558	arg1	biosynthesis					563:574	biosynthesis	563:574	biosynthesis	563:574	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	3	32	from	information	548:558	arg1	context					591:597	physiological context	577:597	physiological context	577:597	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	4	33	theme	cell	774:777	arg1	glycome					787:793	the cell surface glycome	770:793	the cell surface glycome of the living cell	770:812	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	3	34	theme	tag	481:483	arg1	glycans					485:491	tag glycans	481:491	tag glycans with editable chemical functionalities	481:530	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	4	35	dep	use	689:691	arg1	engineered					693:702	engineered	693:702	use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell	689:812	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	2	36	theme	essential	294:302	arg1	processes					315:323	essential biological processes	294:323	essential biological processes	294:323	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	0	37	theme	Glycosyltransferases	60:79	arg1	Substrates					46:55	Specific Substrates	37:55	Specific Substrates of Glycosyltransferases	37:79	Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells.
32325029	4	38	theme	non-natural	642:652	arg1	pathway					677:683	a non-natural substrate biosynthetic pathway	640:683	a non-natural substrate biosynthetic pathway	640:683	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	1	39	theme	experimental	161:172	arg1	strategies					174:183	experimental strategies	161:183	experimental strategies that oversimplify the complex biosynthetic machineries of living cells	161:254	Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells.
32325029	2	40	theme	glycan	342:347	arg1	structure					349:357	glycan structure	342:357	glycan structure	342:357	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	5	41	theme	glycosyltransferase	892:910	arg1	transferases					959:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	5	41	theme	glycosyltransferase	892:910	arg1	family					912:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	3	42	theme	physiological	577:589	arg1	context					591:597	physiological context	577:597	physiological context	577:597	Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure.
32325029	2	43	theme	Protein	257:263	arg1	glycosylation					265:277	Protein glycosylation	257:277	Protein glycosylation	257:277	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	2	44	theme	correlating	330:340	arg1	structure					349:357	glycan structure	342:357	glycan structure	342:357	Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive.
32325029	5	45	theme	human	886:890	arg1	transferases					959:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	the polypeptide N-acetylgalactosaminyl transferases	920:970	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	5	45	theme	human	886:890	arg1	family					912:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	a particularly redundant yet disease-relevant human glycosyltransferase family	840:917	We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases.
32325029	0	46	theme	Living	84:89	arg1	Cells					91:95	Living Cells	84:95	Living Cells	84:95	Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells.
32325029	4	47	theme	cell	809:812	arg1	glycome					787:793	the cell surface glycome	770:793	the cell surface glycome of the living cell	770:812	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32325029	4	48	theme	tagged	751:756	arg1	sugars					758:763	chemically tagged sugars	740:763	chemically tagged sugars	740:763	We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell.
32985651	10	0	theme	binding	1527:1533	arg1	site					1535:1538	the predicted heparin binding site 568RFKRKLPK575	1505:1553	the predicted heparin binding site 568RFKRKLPK575	1505:1553	A docked heparin hexasaccharide interacted well with the predicted heparin binding site 568RFKRKLPK575.
32985651	4	1	from	structures	753:762	arg1	visible					729:735	visible	729:735	visible	729:735	Human DAO did not only bind to various endothelial and epithelial cell lines in vitro, but was also unexpectedly internalized and visible in granule-like structures.
32985651	11	2	theme	clearance	1702:1710	arg1	ASGP-R					1722:1727	ASGP-R	1722:1727	ASGP-R	1722:1727	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	2	theme	clearance	1702:1710	arg1	receptors					1712:1720	the classical clearance receptors	1688:1720	the classical clearance receptors ASGP-R and MR	1688:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	2	theme	clearance	1702:1710	arg1	MR					1733:1734	MR	1733:1734	MR	1733:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	10	3	theme	predicted	1509:1517	arg1	site					1535:1538	the predicted heparin binding site 568RFKRKLPK575	1505:1553	the predicted heparin binding site 568RFKRKLPK575	1505:1553	A docked heparin hexasaccharide interacted well with the predicted heparin binding site 568RFKRKLPK575.
32985651	9	4	theme	heparan	1374:1380	arg1	lines					1409:1413	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	4	theme	heparan	1374:1380	arg1	pgsD-677					1428:1435	pgsD-677	1428:1435	pgsD-677	1428:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	4	theme	heparan	1374:1380	arg1	pgsA-745					1415:1422	pgsA-745	1415:1422	pgsA-745	1415:1422	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	0	5	theme	rapid	72:76	arg1	clearance					78:86	rapid clearance	72:86	rapid clearance in vivo	72:94	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	7	6	theme	involvement	1088:1098	arg1	lack					1080:1083	The lack	1076:1083	The lack of involvement of N-glycans	1076:1111	The lack of involvement of N-glycans was confirmed by testing various glycosylation mutants.
32985651	4	7	theme	cell	665:668	arg1	lines					670:674	epithelial cell lines	654:674	epithelial cell lines	654:674	Human DAO did not only bind to various endothelial and epithelial cell lines in vitro, but was also unexpectedly internalized and visible in granule-like structures.
32985651	9	8	theme	sulfate-deficient	1382:1398	arg1	lines					1409:1413	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	8	theme	sulfate-deficient	1382:1398	arg1	pgsD-677					1428:1435	pgsD-677	1428:1435	pgsD-677	1428:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	8	theme	sulfate-deficient	1382:1398	arg1	pgsA-745					1415:1422	pgsA-745	1415:1422	pgsA-745	1415:1422	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	5	9	theme	mannose	926:932	arg1	residues					934:941	mannose residues	926:941	mannose residues	926:941	The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively.
32985651	8	10	from	internalization	1232:1246	arg1	HUVECs					1276:1281	HUVECs	1276:1281	HUVECs	1276:1281	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	8	10	from	internalization	1232:1246	arg1	cells					1266:1270	HepG2 cells	1260:1270	HepG2 cells	1260:1270	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	6	11	theme	Competition	958:968	arg1	experiments					970:980	Competition experiments	958:980	Competition experiments with ASGP-R and MR ligands	958:1007	Competition experiments with ASGP-R and MR ligands did not block internalization in vitro or rapid clearance in vivo.
32985651	11	12	theme	N-glycan	1661:1668	arg1	interactions					1670:1681	N-glycan interactions	1661:1681	N-glycan interactions with the classical clearance receptors ASGP-R and MR	1661:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	4	13	from	visible	729:735	arg1	structures					753:762	granule-like structures	740:762	granule-like structures	740:762	Human DAO did not only bind to various endothelial and epithelial cell lines in vitro, but was also unexpectedly internalized and visible in granule-like structures.
32985651	9	14	theme	cell	1404:1407	arg1	lines					1409:1413	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	14	theme	cell	1404:1407	arg1	pgsD-677					1428:1435	pgsD-677	1428:1435	pgsD-677	1428:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	14	theme	cell	1404:1407	arg1	pgsA-745					1415:1422	pgsA-745	1415:1422	pgsA-745	1415:1422	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	11	15	theme	classical	1692:1700	arg1	ASGP-R					1722:1727	ASGP-R	1722:1727	ASGP-R	1722:1727	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	15	theme	classical	1692:1700	arg1	receptors					1712:1720	the classical clearance receptors	1688:1720	the classical clearance receptors ASGP-R and MR	1688:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	15	theme	classical	1692:1700	arg1	MR					1733:1734	MR	1733:1734	MR	1733:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	2	16	theme	therapeutic	333:343	arg1	modality					345:352	a new therapeutic modality	327:352	a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis	327:451	No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis.
32985651	11	17	theme	interactions	1670:1681	arg1	independent					1646:1656	independent	1646:1656	independent	1646:1656	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	4	18	theme	granule-like	740:751	arg1	structures					753:762	granule-like structures	740:762	granule-like structures	740:762	Human DAO did not only bind to various endothelial and epithelial cell lines in vitro, but was also unexpectedly internalized and visible in granule-like structures.
32985651	2	19	theme	local	379:383	arg1	histamine					398:406	excess local and systemic histamine	372:406	excess local and systemic histamine	372:406	No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis.
32985651	2	20	theme	systemic	389:396	arg1	histamine					398:406	excess local and systemic histamine	372:406	excess local and systemic histamine	372:406	No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis.
32985651	8	21	theme	molecular	1186:1194	arg1	heparin					1203:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	11	22	dep	receptors	1712:1720	arg1	ASGP-R					1722:1727	ASGP-R	1722:1727	ASGP-R	1722:1727	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	22	dep	receptors	1712:1720	arg1	receptors					1712:1720	the classical clearance receptors	1688:1720	the classical clearance receptors ASGP-R and MR	1688:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	22	dep	receptors	1712:1720	arg1	MR					1733:1734	MR	1733:1734	MR	1733:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	5	23	theme	rhDAO	779:783	arg1	uptake					769:774	The uptake	765:774	The uptake of rhDAO into cells	765:794	The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively.
32985651	5	23	theme	rhDAO	779:783	arg1	dependent					800:808	dependent	800:808	dependent	800:808	The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively.
32985651	11	24	theme	heparan	1767:1773	arg1	proteoglycans					1783:1795	heparan sulfate proteoglycans	1767:1795	heparan sulfate proteoglycans followed by internalization via an unknown receptor	1767:1847	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	0	25	theme	diamine	6:12	arg1	oxidase					14:20	Human diamine oxidase	0:20	Human diamine oxidase cellular binding	0:37	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	9	26	theme	CHO-K1	1322:1327	arg1	cells					1329:1333	CHO-K1 cells	1322:1333	CHO-K1 cells	1322:1333	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	3	27	theme	dose	546:549	arg1	%					537:537	more than 90%	525:537	more than 90% of the dose	525:549	After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min.
32985651	3	27	theme	dose	546:549	arg1	dose					546:549	the dose	542:549	the dose	542:549	After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min.
32985651	6	28	dep	ASGP-R	987:992	arg1	ligands					1001:1007	ligands	1001:1007	ligands	1001:1007	Competition experiments with ASGP-R and MR ligands did not block internalization in vitro or rapid clearance in vivo.
32985651	1	29	theme	Human	176:180	arg1	hDAO					199:202	hDAO	199:202	hDAO	199:202	Human diamine oxidase (hDAO) rapidly inactivates histamine by deamination.
32985651	1	29	theme	Human	176:180	arg1	oxidase					190:196	Human diamine oxidase	176:196	Human diamine oxidase (hDAO)	176:203	Human diamine oxidase (hDAO) rapidly inactivates histamine by deamination.
32985651	0	30	theme	Human	0:4	arg1	oxidase					14:20	Human diamine oxidase	0:20	Human diamine oxidase cellular binding	0:37	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	5	31	theme	terminal	904:911	arg1	galactose					913:921	terminal galactose	904:921	terminal galactose	904:921	The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively.
32985651	2	32	theme	excess	372:377	arg1	histamine					398:406	excess local and systemic histamine	372:406	excess local and systemic histamine	372:406	No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis.
32985651	0	33	theme	cellular	22:29	arg1	binding					31:37	Human diamine oxidase cellular binding	0:37	Human diamine oxidase cellular binding	0:37	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	3	34	theme	intravenous	460:470	arg1	administration					472:485	intravenous administration	460:485	intravenous administration of recombinant hDAO to rats and mice	460:522	After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min.
32985651	0	35	theme	oxidase	14:20	arg1	binding					31:37	Human diamine oxidase cellular binding	0:37	Human diamine oxidase cellular binding	0:37	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	11	36	theme	sulfate	1775:1781	arg1	proteoglycans					1783:1795	heparan sulfate proteoglycans	1767:1795	heparan sulfate proteoglycans followed by internalization via an unknown receptor	1767:1847	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	9	37	dep	glycosaminoglycan-	1351:1368	arg1	the					1347:1349	the	1347:1349	the	1347:1349	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	5	38	theme	mannose	870:876	arg1	MR					888:889	MR	888:889	MR	888:889	The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively.
32985651	5	38	theme	mannose	870:876	arg1	receptor					878:885	the mannose receptor	866:885	the mannose receptor (MR)	866:890	The uptake of rhDAO into cells was dependent on neither the asialoglycoprotein-receptor (ASGP-R) nor the mannose receptor (MR) recognizing terminal galactose or mannose residues, respectively.
32985651	8	39	theme	low	1182:1184	arg1	heparin					1203:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	8	40	theme	HepG2	1260:1264	arg1	cells					1266:1270	HepG2 cells	1260:1270	HepG2 cells	1260:1270	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	10	41	theme	heparin	1461:1467	arg1	hexasaccharide					1469:1482	A docked heparin hexasaccharide	1452:1482	A docked heparin hexasaccharide	1452:1482	A docked heparin hexasaccharide interacted well with the predicted heparin binding site 568RFKRKLPK575.
32985651	7	42	theme	glycosylation	1146:1158	arg1	mutants					1160:1166	various glycosylation mutants	1138:1166	various glycosylation mutants	1138:1166	The lack of involvement of N-glycans was confirmed by testing various glycosylation mutants.
32985651	3	43	theme	plasma	572:577	arg1	pool					579:582	the plasma pool	568:582	the plasma pool	568:582	After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min.
32985651	1	44	theme	diamine	182:188	arg1	hDAO					199:202	hDAO	199:202	hDAO	199:202	Human diamine oxidase (hDAO) rapidly inactivates histamine by deamination.
32985651	1	44	theme	diamine	182:188	arg1	oxidase					190:196	Human diamine oxidase	176:196	Human diamine oxidase (hDAO)	176:203	Human diamine oxidase (hDAO) rapidly inactivates histamine by deamination.
32985651	6	45	theme	rapid	1051:1055	arg1	clearance					1057:1065	rapid clearance	1051:1065	rapid clearance	1051:1065	Competition experiments with ASGP-R and MR ligands did not block internalization in vitro or rapid clearance in vivo.
32985651	10	46	theme	docked	1454:1459	arg1	hexasaccharide					1469:1482	A docked heparin hexasaccharide	1452:1482	A docked heparin hexasaccharide	1452:1482	A docked heparin hexasaccharide interacted well with the predicted heparin binding site 568RFKRKLPK575.
32985651	11	47	theme	rhDAO	1590:1594	arg1	clearance					1596:1604	rhDAO clearance	1590:1604	rhDAO clearance	1590:1604	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	8	48	theme	rhDAO	1251:1255	arg1	internalization					1232:1246	the internalization	1228:1246	the internalization of rhDAO in HepG2 cells and HUVECs	1228:1281	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	8	49	theme	weight	1196:1201	arg1	heparin					1203:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	11	50	theme	unknown	1832:1838	arg1	receptor					1840:1847	an unknown receptor	1829:1847	an unknown receptor	1829:1847	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	0	51	theme	heparan	133:139	arg1	proteoglycan					149:160	heparan sulfate proteoglycan	133:160	heparan sulfate proteoglycan interactions	133:173	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	9	52	dep	lines	1409:1413	arg1	lines					1409:1413	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	52	dep	lines	1409:1413	arg1	pgsD-677					1428:1435	pgsD-677	1428:1435	pgsD-677	1428:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	52	dep	lines	1409:1413	arg1	pgsA-745					1415:1422	pgsA-745	1415:1422	pgsA-745	1415:1422	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	3	53	theme	hDAO	502:505	arg1	administration					472:485	intravenous administration	460:485	intravenous administration of recombinant hDAO to rats and mice	460:522	After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min.
32985651	7	54	theme	N-glycans	1103:1111	arg1	involvement					1088:1098	involvement	1088:1098	involvement of N-glycans	1088:1111	The lack of involvement of N-glycans was confirmed by testing various glycosylation mutants.
32985651	2	55	theme	new	329:331	arg1	modality					345:352	a new therapeutic modality	327:352	a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis	327:451	No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis.
32985651	0	56	theme	proteoglycan	149:160	arg1	interactions					162:173	heparan sulfate proteoglycan interactions	133:173	heparan sulfate proteoglycan interactions	133:173	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	2	57	theme	pharmacokinetic	254:268	arg1	data					270:273	No pharmacokinetic data	251:273	No pharmacokinetic data	251:273	No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis.
32985651	8	58	theme	High	1169:1172	arg1	heparin					1203:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin	1169:1209	High but not low molecular weight heparin strongly reduced the internalization of rhDAO in HepG2 cells and HUVECs.
32985651	0	59	theme	sulfate	141:147	arg1	proteoglycan					149:160	heparan sulfate proteoglycan	133:160	heparan sulfate proteoglycan interactions	133:173	Human diamine oxidase cellular binding and internalization in vitro and rapid clearance in vivo are not mediated by N-glycans but by heparan sulfate proteoglycan interactions.
32985651	3	60	theme	recombinant	490:500	arg1	hDAO					502:505	recombinant hDAO	490:505	recombinant hDAO	490:505	After intravenous administration of recombinant hDAO to rats and mice, more than 90% of the dose disappeared from the plasma pool within 10 min.
32985651	2	61	with	diseases	358:365	arg1	histamine					398:406	excess local and systemic histamine	372:406	excess local and systemic histamine	372:406	No pharmacokinetic data are available to better understand its potential as a new therapeutic modality for diseases with excess local and systemic histamine, like anaphylaxis, urticaria or mastocytosis.
32985651	11	62	theme	cellular	1618:1625	arg1	uptake					1627:1632	cellular uptake	1618:1632	cellular uptake	1618:1632	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	4	63	theme	epithelial	654:663	arg1	lines					670:674	epithelial cell lines	654:674	epithelial cell lines	654:674	Human DAO did not only bind to various endothelial and epithelial cell lines in vitro, but was also unexpectedly internalized and visible in granule-like structures.
32985651	11	64	with	interactions	1670:1681	arg1	ASGP-R					1722:1727	ASGP-R	1722:1727	ASGP-R	1722:1727	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	64	with	interactions	1670:1681	arg1	receptors					1712:1720	the classical clearance receptors	1688:1720	the classical clearance receptors ASGP-R and MR	1688:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	11	64	with	interactions	1670:1681	arg1	MR					1733:1734	MR	1733:1734	MR	1733:1734	These results strongly imply that rhDAO clearance in vivo and cellular uptake in vitro is independent of N-glycan interactions with the classical clearance receptors ASGP-R and MR, but is mediated by binding to heparan sulfate proteoglycans followed by internalization via an unknown receptor.
32985651	10	65	theme	heparin	1519:1525	arg1	site					1535:1538	the predicted heparin binding site 568RFKRKLPK575	1505:1553	the predicted heparin binding site 568RFKRKLPK575	1505:1553	A docked heparin hexasaccharide interacted well with the predicted heparin binding site 568RFKRKLPK575.
32985651	9	66	theme	CHO	1400:1402	arg1	lines					1409:1413	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677	1374:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	66	theme	CHO	1400:1402	arg1	pgsD-677					1428:1435	pgsD-677	1428:1435	pgsD-677	1428:1435	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	9	66	theme	CHO	1400:1402	arg1	pgsA-745					1415:1422	pgsA-745	1415:1422	pgsA-745	1415:1422	Human DAO was readily internalized by CHO-K1 cells, but not by the glycosaminoglycan- and heparan sulfate-deficient CHO cell lines pgsA-745 and pgsD-677, respectively.
32985651	6	67	with	experiments	970:980	arg1	MR					998:999	MR	998:999	MR	998:999	Competition experiments with ASGP-R and MR ligands did not block internalization in vitro or rapid clearance in vivo.
32985651	6	67	with	experiments	970:980	arg1	ASGP-R					987:992	ASGP-R	987:992	ASGP-R	987:992	Competition experiments with ASGP-R and MR ligands did not block internalization in vitro or rapid clearance in vivo.
32985651	7	68	theme	various	1138:1144	arg1	mutants					1160:1166	various glycosylation mutants	1138:1166	various glycosylation mutants	1138:1166	The lack of involvement of N-glycans was confirmed by testing various glycosylation mutants.
34571967	0	0	theme	Inhibitors	79:88	arg1	Effects					47:53	Specific Effects	38:53	Specific Effects of Glycosyl Transferase Inhibitors	38:88	N-Glycomic Analysis of the Cell Shows Specific Effects of Glycosyl Transferase Inhibitors.
34571967	3	1	theme	glycans	319:325	arg1	analysis					294:301	structural analysis	283:301	structural analysis of the released glycans	283:325	However, structural analysis of the released glycans has been limited.
34571967	10	2	theme	viral	1490:1494	arg1	infection					1510:1518	viral and bacterial infection	1490:1518	viral and bacterial infection	1490:1518	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	10	3	theme	cellular	1387:1394	arg1	behavior					1396:1403	the cellular behavior	1383:1403	the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions	1383:1560	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	0	4	theme	Transferase	67:77	arg1	Inhibitors					79:88	Glycosyl Transferase Inhibitors	58:88	Glycosyl Transferase Inhibitors	58:88	N-Glycomic Analysis of the Cell Shows Specific Effects of Glycosyl Transferase Inhibitors.
34571967	6	5	theme	fucosylated	948:958	arg1	glycans					960:966	fucosylated glycans	948:966	fucosylated glycans	948:966	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	6	6	theme	2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic	799:855	arg1	ester					869:873	2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester	799:873	2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans	799:896	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	1	7	theme	metabolic	155:163	arg1	inhibitors					165:174	metabolic inhibitors	155:174	metabolic inhibitors	155:174	Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production.
34571967	10	8	theme	biological	1464:1473	arg1	systems					1475:1481	various biological systems	1456:1481	various biological systems	1456:1481	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	8	9	theme	6-alkynyl	1074:1082	arg1	fucose					1084:1089	The compound 6-alkynyl fucose	1061:1089	The compound 6-alkynyl fucose	1061:1089	The compound 6-alkynyl fucose inhibited some fucosylation but also incorporated into the glycan structure.
34571967	6	10	gly	fucosylated	948:958	arg1	glycans					960:966	fucosylated glycans	948:966	fucosylated glycans	948:966	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	9	11	from	changes	1299:1305	arg1	N-glycome					1314:1322	the N-glycome	1310:1322	the N-glycome for Caco-2	1310:1333	Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2.
34571967	4	12	theme	glycocalyx	457:466	arg1	N-glycans					440:448	the N-glycans	436:448	the N-glycans of the glycocalyx	436:466	In this research, the cell membranes were enriched and the glycans were released to obtain the N-glycans of the glycocalyx.
34571967	8	13	theme	compound	1065:1072	arg1	fucose					1084:1089	The compound 6-alkynyl fucose	1061:1089	The compound 6-alkynyl fucose	1061:1089	The compound 6-alkynyl fucose inhibited some fucosylation but also incorporated into the glycan structure.
34571967	6	14	theme	structures	787:796	arg1	formation					749:757	the formation	745:757	the formation of complex- and hybrid-type structures	745:796	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	10	15	theme	Future	1336:1341	arg1	works					1343:1347	Future works	1336:1347	Future works	1336:1347	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	6	16	theme	6-alkynyl	927:935	arg1	fucose					937:942	6-alkynyl fucose	927:942	6-alkynyl fucose for fucosylated glycans	927:966	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	1	17	from	effect	145:150	arg1	production					186:195	glycan production	179:195	glycan production	179:195	Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production.
34571967	5	18	used	used	568:571	arg2	analysis					478:485	Glycomic analysis	469:485	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column	469:562	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	1	19	theme	inhibitors	165:174	arg1	effect					145:150	the effect	141:150	the effect of metabolic inhibitors on glycan production	141:195	Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production.
34571967	5	20	theme	cell	606:609	arg1	membrane					611:618	the cell membrane	602:618	the cell membrane	602:618	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	9	21	theme	small	1248:1252	arg1	changes					1254:1260	only small changes	1243:1260	only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2	1243:1333	Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2.
34571967	5	22	theme	liquid	493:498	arg1	LC-MS					534:538	LC-MS	534:538	LC-MS	534:538	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	5	22	theme	liquid	493:498	arg1	spectrometry					520:531	liquid chromatography-mass spectrometry	493:531	liquid chromatography-mass spectrometry (LC-MS)	493:539	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	10	23	theme	bacterial	1500:1508	arg1	infection					1510:1518	viral and bacterial infection	1490:1518	viral and bacterial infection	1490:1518	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	6	24	theme	complex-	762:769	arg1	structures					787:796	complex- and hybrid-type structures	762:796	complex- and hybrid-type structures	762:796	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	5	25	theme	chromatography-mass	500:518	arg1	LC-MS					534:538	LC-MS	534:538	LC-MS	534:538	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	5	25	theme	chromatography-mass	500:518	arg1	spectrometry					520:531	liquid chromatography-mass spectrometry	493:531	liquid chromatography-mass spectrometry (LC-MS)	493:539	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	1	26	theme	glycan	179:184	arg1	production					186:195	glycan production	179:195	glycan production	179:195	Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production.
34571967	0	27	theme	N-Glycomic	0:9	arg1	Analysis					11:18	N-Glycomic Analysis	0:18	N-Glycomic Analysis of the Cell	0:30	N-Glycomic Analysis of the Cell Shows Specific Effects of Glycosyl Transferase Inhibitors.
34571967	10	28	theme	various	1456:1462	arg1	systems					1475:1481	various biological systems	1456:1481	various biological systems	1456:1481	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	1	29	theme	Glycomic	91:98	arg1	methods					110:116	Glycomic profiling methods	91:116	Glycomic profiling methods	91:116	Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production.
34571967	4	30	theme	cell	367:370	arg1	membranes					372:380	the cell membranes	363:380	the cell membranes	363:380	In this research, the cell membranes were enriched and the glycans were released to obtain the N-glycans of the glycocalyx.
34571967	1	31	theme	profiling	100:108	arg1	methods					110:116	Glycomic profiling methods	91:116	Glycomic profiling methods	91:116	Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production.
34571967	2	32	used	used	228:231	arg2	inhibitors					204:213	These inhibitors	198:213	These inhibitors	198:213	These inhibitors are commonly used to alter the cell surface glycosylation.
34571967	9	33	theme	membrane	1203:1210	arg1	analysis					1178:1185	Proteomic analysis	1168:1185	Proteomic analysis of the enriched membrane for the four inhibitors	1168:1234	Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2.
34571967	3	34	theme	structural	283:292	arg1	analysis					294:301	structural analysis	283:301	structural analysis of the released glycans	283:325	However, structural analysis of the released glycans has been limited.
34571967	9	35	theme	large	1293:1297	arg1	changes					1299:1305	large changes	1293:1305	large changes in the N-glycome for Caco-2	1293:1333	Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2.
34571967	6	36	gly	sialylated	879:888	arg1	glycans					890:896	sialylated glycans	879:896	sialylated glycans	879:896	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	10	37	theme	glycosylation	1439:1451	arg1	alteration					1425:1434	the alteration	1421:1434	the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions	1421:1560	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	5	38	theme	Glycomic	469:476	arg1	analysis					478:485	Glycomic analysis	469:485	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column	469:562	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	0	39	theme	Cell	27:30	arg1	Analysis					11:18	N-Glycomic Analysis	0:18	N-Glycomic Analysis of the Cell	0:30	N-Glycomic Analysis of the Cell Shows Specific Effects of Glycosyl Transferase Inhibitors.
34571967	10	40	theme	drug	1521:1524	arg1	binding					1526:1532	drug binding	1521:1532	drug binding	1521:1532	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	9	41	theme	Proteomic	1168:1176	arg1	analysis					1178:1185	Proteomic analysis	1168:1185	Proteomic analysis of the enriched membrane for the four inhibitors	1168:1234	Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2.
34571967	7	42	theme	mannose	1046:1052	arg1	types					1054:1058	high mannose types	1041:1058	high mannose types	1041:1058	Kifunensine was the most effective, converting nearly 95% of glycans to high mannose types.
34571967	8	43	theme	glycan	1150:1155	arg1	structure					1157:1165	the glycan structure	1146:1165	the glycan structure	1146:1165	The compound 6-alkynyl fucose inhibited some fucosylation but also incorporated into the glycan structure.
34571967	6	44	theme	sialylated	879:888	arg1	glycans					890:896	sialylated glycans	879:896	sialylated glycans	879:896	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	10	45	from	alteration	1425:1434	arg1	systems					1475:1481	various biological systems	1456:1481	various biological systems	1456:1481	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	0	46	theme	Specific	38:45	arg1	Effects					47:53	Specific Effects	38:53	Specific Effects of Glycosyl Transferase Inhibitors	38:88	N-Glycomic Analysis of the Cell Shows Specific Effects of Glycosyl Transferase Inhibitors.
34571967	3	47	theme	released	310:317	arg1	glycans					319:325	the released glycans	306:325	the released glycans	306:325	However, structural analysis of the released glycans has been limited.
34571967	5	48	theme	PGC	548:550	arg1	column					557:562	a PGC chip column	546:562	a PGC chip column	546:562	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	6	49	theme	cells	642:646	arg1	Glycans					621:627	Glycans	621:627	Glycans of untreated cells	621:646	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	5	50	theme	chip	552:555	arg1	column					557:562	a PGC chip column	546:562	a PGC chip column	546:562	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	1	51	used	used	123:126	arg2	methods					110:116	Glycomic profiling methods	91:116	Glycomic profiling methods	91:116	Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production.
34571967	7	52	theme	high	1041:1044	arg1	types					1054:1058	high mannose types	1041:1058	high mannose types	1041:1058	Kifunensine was the most effective, converting nearly 95% of glycans to high mannose types.
34571967	6	53	theme	methyl	862:867	arg1	ester					869:873	2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester	799:873	2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans	799:896	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	2	54	theme	surface	251:257	arg1	glycosylation					259:271	the cell surface glycosylation	242:271	the cell surface glycosylation	242:271	These inhibitors are commonly used to alter the cell surface glycosylation.
34571967	9	55	theme	enriched	1194:1201	arg1	membrane					1203:1210	the enriched membrane	1190:1210	the enriched membrane for the four inhibitors	1190:1234	Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2.
34571967	9	56	from	changes	1254:1260	arg1	proteome					1269:1276	the proteome	1265:1276	the proteome accompanied by large changes in the N-glycome for Caco-2	1265:1333	Proteomic analysis of the enriched membrane for the four inhibitors showed only small changes in the proteome accompanied by large changes in the N-glycome for Caco-2.
34571967	6	57	theme	hybrid-type	775:785	arg1	structures					787:796	complex- and hybrid-type structures	762:796	complex- and hybrid-type structures	762:796	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	6	58	theme	cells	676:680	arg1	glycans					665:671	glycans	665:671	glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans	665:966	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	0	59	theme	Glycosyl	58:65	arg1	Inhibitors					79:88	Glycosyl Transferase Inhibitors	58:88	Glycosyl Transferase Inhibitors	58:88	N-Glycomic Analysis of the Cell Shows Specific Effects of Glycosyl Transferase Inhibitors.
34571967	6	60	theme	acid	857:860	arg1	ester					869:873	2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester	799:873	2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans	799:896	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	2	61	theme	cell	246:249	arg1	glycosylation					259:271	the cell surface glycosylation	242:271	the cell surface glycosylation	242:271	These inhibitors are commonly used to alter the cell surface glycosylation.
34571967	7	62	theme	glycans	1030:1036	arg1	glycans					1030:1036	glycans	1030:1036	glycans	1030:1036	Kifunensine was the most effective, converting nearly 95% of glycans to high mannose types.
34571967	7	62	theme	glycans	1030:1036	arg1	%					1025:1025	nearly 95%	1016:1025	nearly 95% of glycans	1016:1036	Kifunensine was the most effective, converting nearly 95% of glycans to high mannose types.
34571967	5	63	from	structures	588:597	arg1	membrane					611:618	the cell membrane	602:618	the cell membrane	602:618	Glycomic analysis using liquid chromatography-mass spectrometry (LC-MS) with a PGC chip column was used to profile the structures in the cell membrane.
34571967	6	64	theme	untreated	632:640	arg1	cells					642:646	untreated cells	632:646	untreated cells	632:646	Glycans of untreated cells were compared to glycans of cells treated with inhibitors, including kifunensine, which inhibits the formation of complex- and hybrid-type structures, 2,4,7,8,9-Penta-O-acetyl-N-acetyl-3-fluoro-b-d-neuraminic acid methyl ester for sialylated glycans, 2-deoxy-2-fluorofucose, and 6-alkynyl fucose for fucosylated glycans.
34571967	10	65	dep	infection	1510:1518	arg1	e.g.					1484:1487	e.g.	1484:1487	e.g.	1484:1487	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34571967	10	66	theme	cell-cell	1539:1547	arg1	interactions					1549:1560	cell-cell interactions	1539:1560	cell-cell interactions	1539:1560	Future works may use these inhibitors to study the cellular behavior associated with the alteration of glycosylation in various biological systems, e.g., viral and bacterial infection, drug binding, and cell-cell interactions.
34545811	8	0	theme	potential	1591:1599	arg1	significance					1601:1612	potential significance	1591:1612	potential significance for synaptic plasticity, addiction, and disease	1591:1660	This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.
34545811	3	1	theme	alterations	524:534	arg1	basis					493:497	the basis	489:497	the basis of these N-glycosylation alterations	489:534	In exploring the basis of these N-glycosylation alterations, we discovered that they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite.
34545811	8	2	theme	synaptic	1618:1625	arg1	plasticity					1627:1636	synaptic plasticity	1618:1636	synaptic plasticity	1618:1636	This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.
34545811	2	3	theme	dendrites	361:369	arg1	glycoproteins					344:356	surface glycoproteins	336:356	surface glycoproteins of dendrites	336:369	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	2	4	from	N-glycans	323:331	arg1	glycoproteins					344:356	surface glycoproteins	336:356	surface glycoproteins of dendrites	336:369	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	7	5	theme	system	1441:1446	arg1	activity					1388:1395	the activity	1384:1395	the activity of the dendrite's satellite micro-secretory system	1384:1446	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	7	6	theme	Golgi	1529:1533	arg1	satellites					1535:1544	peripheral Golgi satellites	1518:1544	peripheral Golgi satellites	1518:1544	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	6	7	from	changes	1151:1157	arg1	surface					1176:1182	the dendritic surface	1162:1182	the dendritic surface of excited neurons	1162:1201	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	6	8	theme	neurotransmitter	1286:1301	arg1	receptors					1345:1353	nicotinic acetylcholine receptors	1321:1353	nicotinic acetylcholine receptors	1321:1353	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	6	8	theme	neurotransmitter	1286:1301	arg1	receptors					1303:1311	neurotransmitter receptors	1286:1311	neurotransmitter receptors such as nicotinic acetylcholine receptors	1286:1353	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	4	9	theme	exit	771:774	arg1	sites					776:780	endoplasmic reticulum (ER) exit sites	744:780	endoplasmic reticulum (ER) exit sites	744:780	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	6	10	theme	acetylcholine	1331:1343	arg1	receptors					1345:1353	nicotinic acetylcholine receptors	1321:1353	nicotinic acetylcholine receptors	1321:1353	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	4	11	theme	early	786:790	arg1	endosomes					792:800	early endosomes	786:800	early endosomes	786:800	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	7	12	theme	glycan	1492:1497	arg1	modifications					1499:1511	glycan modifications	1492:1511	glycan modifications into peripheral Golgi satellites	1492:1544	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	4	13	theme	reticulum	756:764	arg1	sites					776:780	endoplasmic reticulum (ER) exit sites	744:780	endoplasmic reticulum (ER) exit sites	744:780	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	6	14	theme	nicotinic	1321:1329	arg1	receptors					1345:1353	nicotinic acetylcholine receptors	1321:1353	nicotinic acetylcholine receptors	1321:1353	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	8	15	theme	neuronal	1570:1577	arg1	surface					1579:1585	the neuronal surface	1566:1585	the neuronal surface	1566:1585	This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.
34545811	5	16	theme	secretory	1038:1046	arg1	pathway					1048:1054	the secretory pathway	1034:1054	the secretory pathway	1034:1054	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	5	17	theme	glycosylation	911:923	arg1	They					885:888	They	885:888	They	885:888	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	5	17	theme	glycosylation	911:923	arg1	stations					925:932	distal glycosylation stations	904:932	distal glycosylation stations in dendrites	904:945	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	4	18	theme	neuronal	693:700	arg1	excitation					702:711	neuronal excitation	693:711	neuronal excitation	693:711	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	5	19	gly	glycoproteins	1004:1016	arg1	glycoproteins					1004:1016	newly synthesized glycoproteins	986:1016	newly synthesized glycoproteins passing through the secretory pathway	986:1054	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	0	20	theme	Activity-dependent	0:17	arg1	formation					35:43	Activity-dependent Golgi satellite formation	0:43	Activity-dependent Golgi satellite formation in dendrites	0:56	Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
34545811	5	21	theme	distal	904:909	arg1	They					885:888	They	885:888	They	885:888	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	5	21	theme	distal	904:909	arg1	stations					925:932	distal glycosylation stations	904:932	distal glycosylation stations in dendrites	904:945	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	0	22	theme	Golgi	19:23	arg1	formation					35:43	Activity-dependent Golgi satellite formation	0:43	Activity-dependent Golgi satellite formation in dendrites	0:56	Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
34545811	2	23	dep	activation	464:473	arg1	response					433:440	response	433:440	response	433:440	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	1	24	theme	Activity-driven	103:117	arg1	changes					119:125	Activity-driven changes	103:125	Activity-driven changes in the neuronal surface glycoproteome	103:163	Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear.
34545811	4	25	with	association	727:737	arg1	sites					776:780	endoplasmic reticulum (ER) exit sites	744:780	endoplasmic reticulum (ER) exit sites	744:780	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	4	25	with	association	727:737	arg1	endosomes					792:800	early endosomes	786:800	early endosomes	786:800	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	2	26	theme	mature	394:399	arg1	forms					401:405	mature forms	394:405	mature forms containing sialic acid in response to increased neuronal activation	394:473	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	2	27	theme	neuronal	455:462	arg1	activation					464:473	increased neuronal activation	445:473	increased neuronal activation	445:473	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	5	28	theme	synthesized	992:1002	arg1	glycoproteins					1004:1016	newly synthesized glycoproteins	986:1016	newly synthesized glycoproteins passing through the secretory pathway	986:1054	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	2	29	theme	increased	445:453	arg1	activation					464:473	increased neuronal activation	445:473	increased neuronal activation	445:473	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	5	30	from	sugars	969:974	arg1	glycoproteins					1004:1016	newly synthesized glycoproteins	986:1016	newly synthesized glycoproteins passing through the secretory pathway	986:1054	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	5	30	from	sugars	969:974	arg1	glycoproteins					1070:1082	surface glycoproteins	1062:1082	surface glycoproteins taken up from the endocytic pathway	1062:1118	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	4	31	theme	structural	858:867	arg1	GM130					878:882	GM130	878:882	GM130	878:882	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	4	31	theme	structural	858:867	arg1	protein					869:875	the Golgi structural protein	848:875	the Golgi structural protein	848:875	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	0	32	theme	satellite	25:33	arg1	formation					35:43	Activity-dependent Golgi satellite formation	0:43	Activity-dependent Golgi satellite formation in dendrites	0:56	Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
34545811	6	33	from	changes	1275:1281	arg1	receptors					1345:1353	nicotinic acetylcholine receptors	1321:1353	nicotinic acetylcholine receptors	1321:1353	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	6	33	from	changes	1275:1281	arg1	receptors					1303:1311	neurotransmitter receptors	1286:1311	neurotransmitter receptors such as nicotinic acetylcholine receptors	1286:1353	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	4	34	theme	Golgi	657:661	arg1	satellites					663:672	Golgi satellites	657:672	Golgi satellites that formed during neuronal excitation	657:711	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	3	35	theme	N-glycosylation	508:522	arg1	alterations					524:534	these N-glycosylation alterations	502:534	these N-glycosylation alterations	502:534	In exploring the basis of these N-glycosylation alterations, we discovered that they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite.
34545811	6	36	theme	excited	1187:1193	arg1	neurons					1195:1201	excited neurons	1187:1201	excited neurons	1187:1201	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	3	37	theme	satellites	611:620	arg1	growth					577:582	growth	577:582	growth	577:582	In exploring the basis of these N-glycosylation alterations, we discovered that they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite.
34545811	3	37	theme	satellites	611:620	arg1	proliferation					588:600	proliferation	588:600	proliferation	588:600	In exploring the basis of these N-glycosylation alterations, we discovered that they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite.
34545811	1	38	theme	related	224:230	arg1	diseases					232:239	related diseases	224:239	related diseases	224:239	Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear.
34545811	6	39	theme	major	1145:1149	arg1	changes					1151:1157	major changes	1145:1157	major changes in the dendritic surface of excited neurons	1145:1201	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	4	40	theme	endoplasmic	744:754	arg1	reticulum					756:764	endoplasmic reticulum	744:764	endoplasmic reticulum (ER) exit sites	744:780	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	4	40	theme	endoplasmic	744:754	arg1	ER					767:768	ER	767:768	ER	767:768	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	4	41	theme	Golgi	852:856	arg1	GM130					878:882	GM130	878:882	GM130	878:882	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	4	41	theme	Golgi	852:856	arg1	protein					869:875	the Golgi structural protein	848:875	the Golgi structural protein	848:875	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	2	42	theme	sialic	418:423	arg1	acid					425:428	sialic acid	418:428	sialic acid	418:428	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	5	43	gly	glycoproteins	1070:1082	arg1	glycoproteins					1070:1082	surface glycoproteins	1062:1082	surface glycoproteins taken up from the endocytic pathway	1062:1118	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	4	44	contain	contained	806:814	arg1	satellites					663:672	Golgi satellites	657:672	Golgi satellites that formed during neuronal excitation	657:711	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	4	44	contain	contained	806:814	arg2	machinery					830:838	glycosylation machinery	816:838	glycosylation machinery	816:838	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	2	45	gly	glycoproteins	344:356	arg1	glycoproteins					344:356	surface glycoproteins	336:356	surface glycoproteins of dendrites	336:369	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	2	46	contain	containing	407:416	arg1	forms					401:405	mature forms	394:405	mature forms containing sialic acid in response to increased neuronal activation	394:473	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	2	46	contain	containing	407:416	arg2	acid					425:428	sialic acid	418:428	sialic acid	418:428	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	1	47	dep	synapse	189:195	arg1	formation					197:205	formation	197:205	formation	197:205	Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear.
34545811	6	48	theme	dendritic	1166:1174	arg1	surface					1176:1182	the dendritic surface	1162:1182	the dendritic surface of excited neurons	1162:1201	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	1	49	theme	neuronal	134:141	arg1	glycoproteome					151:163	the neuronal surface glycoproteome	130:163	the neuronal surface glycoproteome	130:163	Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear.
34545811	6	50	theme	lectins	1236:1242	arg1	binding					1214:1220	binding	1214:1220	binding	1214:1220	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	6	50	theme	lectins	1236:1242	arg1	uptake					1226:1231	uptake	1226:1231	uptake	1226:1231	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	5	51	theme	endocytic	1102:1110	arg1	pathway					1112:1118	the endocytic pathway	1098:1118	the endocytic pathway	1098:1118	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	3	52	theme	Golgi	605:609	arg1	satellites					611:620	Golgi satellites	605:620	Golgi satellites scattered throughout the dendrite	605:654	In exploring the basis of these N-glycosylation alterations, we discovered that they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite.
34545811	1	53	theme	surface	143:149	arg1	glycoproteome					151:163	the neuronal surface glycoproteome	130:163	the neuronal surface glycoproteome	130:163	Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear.
34545811	6	54	theme	functional	1264:1273	arg1	changes					1275:1281	functional changes	1264:1281	functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors	1264:1353	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	7	55	theme	micro-secretory	1425:1439	arg1	system					1441:1446	the dendrite's satellite micro-secretory system	1400:1446	the dendrite's satellite micro-secretory system	1400:1446	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	2	56	theme	surface	336:342	arg1	glycoproteins					344:356	surface glycoproteins	336:356	surface glycoproteins of dendrites	336:369	Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation.
34545811	8	57	contain	has	1587:1589	arg1	remodeling					1552:1561	This remodeling	1547:1561	This remodeling of the neuronal surface	1547:1585	This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.
34545811	8	57	contain	has	1587:1589	arg2	significance					1601:1612	potential significance	1591:1612	potential significance for synaptic plasticity, addiction, and disease	1591:1660	This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.
34545811	7	58	theme	peripheral	1518:1527	arg1	satellites					1535:1544	peripheral Golgi satellites	1518:1544	peripheral Golgi satellites	1518:1544	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	7	59	theme	Neural	1356:1361	arg1	activity					1363:1370	Neural activity	1356:1370	Neural activity	1356:1370	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	4	60	theme	glycosylation	816:828	arg1	machinery					830:838	glycosylation machinery	816:838	glycosylation machinery	816:838	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	7	61	theme	Golgi	1466:1470	arg1	enzymes					1472:1478	Golgi enzymes	1466:1478	Golgi enzymes involved in glycan modifications into peripheral Golgi satellites	1466:1544	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	6	62	theme	neurons	1195:1201	arg1	surface					1176:1182	the dendritic surface	1162:1182	the dendritic surface of excited neurons	1162:1201	These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors.
34545811	0	63	theme	surface	80:86	arg1	glycoproteome					88:100	the neuronal surface glycoproteome	67:100	the neuronal surface glycoproteome	67:100	Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
34545811	8	64	theme	surface	1579:1585	arg1	remodeling					1552:1561	This remodeling	1547:1561	This remodeling of the neuronal surface	1547:1585	This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.
34545811	5	65	theme	surface	1062:1068	arg1	glycoproteins					1070:1082	surface glycoproteins	1062:1082	surface glycoproteins taken up from the endocytic pathway	1062:1118	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	5	66	from	stations	925:932	arg1	dendrites					937:945	dendrites	937:945	dendrites	937:945	They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway.
34545811	4	67	theme	close	721:725	arg1	association					727:737	close association	721:737	close association with endoplasmic reticulum (ER) exit sites and early endosomes	721:800	Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130.
34545811	1	68	from	changes	119:125	arg1	glycoproteome					151:163	the neuronal surface glycoproteome	130:163	the neuronal surface glycoproteome	130:163	Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear.
34545811	0	69	theme	neuronal	71:78	arg1	glycoproteome					88:100	the neuronal surface glycoproteome	67:100	the neuronal surface glycoproteome	67:100	Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
34545811	0	70	from	formation	35:43	arg1	dendrites					48:56	dendrites	48:56	dendrites	48:56	Activity-dependent Golgi satellite formation in dendrites reshapes the neuronal surface glycoproteome.
34545811	7	71	theme	satellite	1415:1423	arg1	system					1441:1446	the dendrite's satellite micro-secretory system	1400:1446	the dendrite's satellite micro-secretory system	1400:1446	Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites.
34545811	1	72	theme	mechanistic	252:262	arg1	basis					264:268	their mechanistic basis	246:268	their mechanistic basis	246:268	Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear.
32028604	4	0	theme	pyrophosphorylases-galactose	882:909	arg1	pyrophosphorylase					1003:1019	UDP-N-acetylglucosamine pyrophosphorylase	979:1019	UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1)	979:1031	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	0	theme	pyrophosphorylases-galactose	882:909	arg1	GALT					931:934	GALT	931:934	GALT	931:934	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	0	theme	pyrophosphorylases-galactose	882:909	arg1	pyro-phosphorylase					911:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase	871:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT)	871:935	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	0	theme	pyrophosphorylases-galactose	882:909	arg1	pyrophosphorylase					950:966	UDP-glucose pyrophosphorylase	938:966	UDP-glucose pyrophosphorylase (UGP2)	938:973	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	2	1	from	processes	424:432	arg1	cells					447:451	cancerous cells	437:451	cancerous cells	437:451	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	3	2	theme	therapeutic	692:702	arg1	targets					704:710	therapeutic targets	692:710	therapeutic targets for cancers	692:722	We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers.
32028604	3	2	theme	therapeutic	692:702	arg1	enzymes					585:591	the enzymes	581:591	the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis,	581:675	We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers.
32028604	5	3	from	Gly116	1186:1191	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	3	from	Gly116	1186:1191	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	3	from	Gly116	1186:1191	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	3	from	Gly116	1186:1191	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	6	4	theme	GAL-012-2	1282:1290	arg1	One					1255:1257	One	1255:1257	One	1255:1257	One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2.
32028604	6	4	theme	GAL-012-2	1282:1290	arg1	GAL-012-2					1282:1290	GAL-012 derivatives GAL-012-2	1262:1290	GAL-012 derivatives GAL-012-2	1262:1290	One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2.
32028604	7	5	from	µM	1524:1525	arg1	effects					1482:1488	no effects	1479:1488	no effects on normal skin fibroblasts at 200 µM	1479:1525	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	4	6	theme	small	855:859	arg1	family					861:866	a small family	853:866	a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1)	853:1031	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	10	7	from	relationships	1863:1875	arg1	killing					1941:1947	killing	1941:1947	killing	1941:1947	Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively.
32028604	7	8	theme	cells	1419:1423	arg1	growth					1405:1410	the growth	1401:1410	the growth of PC3 cells	1401:1423	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	5	9	from	Lys127	1197:1202	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	9	from	Lys127	1197:1202	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	9	from	Lys127	1197:1202	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	9	from	Lys127	1197:1202	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	11	10	theme	unique	2009:2014	arg1	scaffold					2016:2023	its unique scaffold	2005:2023	its unique scaffold	2005:2023	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	9	11	from	roles	1807:1811	arg1	inhibition					1830:1839	cancer growth inhibition	1816:1839	cancer growth inhibition	1816:1839	siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition.
32028604	11	12	theme	small	2040:2044	arg1	size					2046:2049	relatively small size	2029:2049	relatively small size	2029:2049	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	1	13	theme	anti-cancer	139:149	arg1	efforts					160:166	recent anti-cancer research efforts	132:166	recent anti-cancer research efforts	132:166	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	4	14	theme	UDP-glucose	938:948	arg1	pyro-phosphorylase					911:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase	871:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT)	871:935	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	14	theme	UDP-glucose	938:948	arg1	UGP2					969:972	UGP2	969:972	UGP2	969:972	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	14	theme	UDP-glucose	938:948	arg1	pyrophosphorylase					950:966	UDP-glucose pyrophosphorylase	938:966	UDP-glucose pyrophosphorylase (UGP2)	938:973	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	15	theme	virtual	749:755	arg1	screening					757:765	structure-based virtual screening	733:765	structure-based virtual screening	733:765	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	6	16	theme	inhibitory	1314:1323	arg1	activity					1325:1332	the inhibitory activity	1310:1332	the inhibitory activity against GALT and UGP2	1310:1354	One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2.
32028604	3	17	theme	glycosyl	639:646	arg1	UDP-hexoses					626:636	UDP-hexoses	626:636	UDP-hexoses	626:636	We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers.
32028604	3	17	theme	glycosyl	639:646	arg1	donors					648:653	glycosyl donors	639:653	glycosyl donors for glycan synthesis	639:674	We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers.
32028604	2	18	theme	cancer	507:512	arg1	tumorigenesis					514:526	cancer tumorigenesis	507:526	cancer tumorigenesis	507:526	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	10	19	theme	cancer	1958:1963	arg1	cells					1965:1969	cultured cancer cells	1949:1969	cultured cancer cells	1949:1969	Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively.
32028604	0	20	theme	Anticancer	79:88	arg1	Pyrophosphorylases					57:74	Multi-UDP-hexose Pyrophosphorylases	40:74	Multi-UDP-hexose Pyrophosphorylases	40:74	Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.
32028604	0	20	theme	Anticancer	79:88	arg1	Agents					90:95	Anticancer Agents	79:95	Anticancer Agents	79:95	Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.
32028604	0	21	theme	Novel	13:17	arg1	Inhibitors					19:28	Novel Inhibitors	13:28	Novel Inhibitors	13:28	Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.
32028604	1	22	theme	broad-based	187:197	arg1	chemotherapy					199:210	broad-based chemotherapy	187:210	broad-based chemotherapy to targeted therapy	187:230	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	4	23	theme	UDP-N-acetylglucosamine	979:1001	arg1	pyrophosphorylase					1003:1019	UDP-N-acetylglucosamine pyrophosphorylase	979:1019	UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1)	979:1031	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	23	theme	UDP-N-acetylglucosamine	979:1001	arg1	pyro-phosphorylase					911:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase	871:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT)	871:935	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	23	theme	UDP-N-acetylglucosamine	979:1001	arg1	AGX1/UAP1					1022:1030	AGX1/UAP1	1022:1030	AGX1/UAP1	1022:1030	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	5	24	theme	binding	1134:1140	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	24	theme	binding	1134:1140	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	24	theme	binding	1134:1140	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	24	theme	binding	1134:1140	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	10	25	from	bortezomib	1921:1930	arg1	killing					1941:1947	killing	1941:1947	killing	1941:1947	Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively.
32028604	2	26	theme	altered	454:460	arg1	glycosylation					462:474	altered glycosylation	454:474	altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance	454:558	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	11	27	theme	anti-cancer	2157:2167	arg1	drug					2169:2172	a safe, effective, multi-target anti-cancer drug	2125:2172	a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics	2125:2250	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	1	28	theme	treatment	110:118	arg1	toxicities					120:129	treatment toxicities	110:129	treatment toxicities	110:129	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	8	29	theme	Western	1528:1534	arg1	analysis					1541:1548	Western blot analysis	1528:1548	Western blot analysis	1528:1548	Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells.
32028604	5	30	from	sites	1142:1146	arg1	Trp190					1159:1164	Trp190	1159:1164	Trp190	1159:1164	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	30	from	sites	1142:1146	arg1	Lys127					1197:1202	Lys127	1197:1202	Lys127	1197:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	30	from	sites	1142:1146	arg1	Gly116					1186:1191	Gly116	1186:1191	Gly116	1186:1191	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	30	from	sites	1142:1146	arg1	Ser192					1170:1175	Ser192	1170:1175	Ser192	1170:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	11	31	with	combination	2216:2226	arg1	therapeutics					2239:2250	known therapeutics	2233:2250	known therapeutics	2233:2250	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	2	32	theme	metabolic	414:422	arg1	processes					424:432	the altered metabolic processes	402:432	the altered metabolic processes in cancerous cells	402:451	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	5	33	from	Ser192	1170:1175	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	33	from	Ser192	1170:1175	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	33	from	Ser192	1170:1175	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	33	from	Ser192	1170:1175	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	1	34	theme	new	328:330	arg1	venues					332:337	new venues	328:337	new venues for targeted intervention	328:363	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	1	34	theme	new	328:330	arg1	metabolism					278:287	altered cellular metabolism	261:287	altered cellular metabolism in cancerous cells	261:306	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	4	35	theme	µM	1052:1053	arg1	IC50					1041:1044	an IC50	1038:1044	an IC50 of 30 µM	1038:1053	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	8	36	theme	reduced	1559:1565	arg1	expression					1567:1576	reduced expression	1559:1576	reduced expression of pAKT (Ser473), pAKT (Thr308)	1559:1608	Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells.
32028604	9	37	theme	respective	1691:1700	arg1	genes					1702:1706	the respective genes	1687:1706	the respective genes encoding the pyrophosphorylases	1687:1738	siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition.
32028604	5	38	from	Trp190	1159:1164	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	38	from	Trp190	1159:1164	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	38	from	Trp190	1159:1164	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	38	from	Trp190	1159:1164	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	7	39	theme	skin	1500:1503	arg1	fibroblasts					1505:1515	normal skin fibroblasts	1493:1515	normal skin fibroblasts	1493:1515	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	5	40	theme	docking	1074:1080	arg1	studies					1082:1088	The computational docking studies	1056:1088	The computational docking studies	1056:1088	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	3	41	theme	UDP-hexoses	626:636	arg1	biosynthesis					610:621	the biosynthesis	606:621	the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis,	606:675	We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers.
32028604	4	42	theme	chemical	812:819	arg1	fragment					821:828	a drug-like chemical fragment	800:828	a drug-like chemical fragment	800:828	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	42	theme	chemical	812:819	arg1	GAL-012					831:837	GAL-012	831:837	GAL-012	831:837	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	7	43	with	EC50	1460:1463	arg1	effects					1482:1488	no effects	1479:1488	no effects on normal skin fibroblasts at 200 µM	1479:1525	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	9	44	theme	cancer	1816:1821	arg1	inhibition					1830:1839	cancer growth inhibition	1816:1839	cancer growth inhibition	1816:1839	siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition.
32028604	1	45	theme	altered	261:267	arg1	venues					332:337	new venues	328:337	new venues for targeted intervention	328:363	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	1	45	theme	altered	261:267	arg1	metabolism					278:287	altered cellular metabolism	261:287	altered cellular metabolism in cancerous cells	261:306	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	2	46	theme	due	476:478	arg1	glycosylation					462:474	altered glycosylation	454:474	altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance	454:558	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	5	47	theme	AGX1/UAP1	1209:1217	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	47	theme	AGX1/UAP1	1209:1217	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	47	theme	AGX1/UAP1	1209:1217	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	47	theme	AGX1/UAP1	1209:1217	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	7	48	theme	µM	1471:1472	arg1	EC50					1460:1463	an EC50	1457:1463	an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM	1457:1525	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	4	49	theme	UDP-hexose	871:880	arg1	pyrophosphorylase					1003:1019	UDP-N-acetylglucosamine pyrophosphorylase	979:1019	UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1)	979:1031	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	49	theme	UDP-hexose	871:880	arg1	GALT					931:934	GALT	931:934	GALT	931:934	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	49	theme	UDP-hexose	871:880	arg1	pyro-phosphorylase					911:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase	871:928	UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT)	871:935	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	49	theme	UDP-hexose	871:880	arg1	pyrophosphorylase					950:966	UDP-glucose pyrophosphorylase	938:966	UDP-glucose pyrophosphorylase (UGP2)	938:973	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	11	50	theme	early	2082:2086	arg1	GAL-012					2052:2058	GAL-012	2052:2058	GAL-012	2052:2058	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	11	50	theme	early	2082:2086	arg1	chemotype					2088:2096	a promising early chemotype	2070:2096	a promising early chemotype for optimization	2070:2113	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	10	51	theme	synergistic	1851:1861	arg1	relationships					1863:1875	synergistic relationships	1851:1875	synergistic relationships between GAL-012 and tunicamycin	1851:1907	Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively.
32028604	1	52	theme	cancerous	292:300	arg1	cells					302:306	cancerous cells	292:306	cancerous cells	292:306	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	4	53	theme	pyro-phosphorylase	911:928	arg1	family					861:866	a small family	853:866	a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1)	853:1031	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	6	54	theme	derivatives	1270:1280	arg1	GAL-012-2					1282:1290	GAL-012 derivatives GAL-012-2	1262:1290	GAL-012 derivatives GAL-012-2	1262:1290	One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2.
32028604	11	55	theme	safe	2127:2130	arg1	drug					2169:2172	a safe, effective, multi-target anti-cancer drug	2125:2172	a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics	2125:2250	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	7	56	theme	dose-dependent	1430:1443	arg1	manner					1445:1450	a dose-dependent manner	1428:1450	a dose-dependent manner	1428:1450	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	8	57	theme	treated	1646:1652	arg1	cells					1654:1658	the treated cells	1642:1658	the treated cells	1642:1658	Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells.
32028604	1	58	theme	targeted	215:222	arg1	therapy					224:230	targeted therapy	215:230	targeted therapy	215:230	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	11	59	theme	promising	2072:2080	arg1	GAL-012					2052:2058	GAL-012	2052:2058	GAL-012	2052:2058	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	11	59	theme	promising	2072:2080	arg1	chemotype					2088:2096	a promising early chemotype	2070:2096	a promising early chemotype for optimization	2070:2113	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	11	60	theme	known	2233:2237	arg1	therapeutics					2239:2250	known therapeutics	2233:2250	known therapeutics	2233:2250	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	2	61	from	roles	498:502	arg1	metastasis					529:538	metastasis	529:538	metastasis	529:538	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	2	61	from	roles	498:502	arg1	resistance					549:558	drug resistance	544:558	drug resistance	544:558	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	2	61	from	roles	498:502	arg1	tumorigenesis					514:526	cancer tumorigenesis	507:526	cancer tumorigenesis	507:526	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	7	62	theme	PC3	1415:1417	arg1	cells					1419:1423	PC3 cells	1415:1423	PC3 cells	1415:1423	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	1	63	from	metabolism	278:287	arg1	cells					302:306	cancerous cells	292:306	cancerous cells	292:306	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	5	64	theme	GAL-012	1119:1125	arg1	interaction					1104:1114	the interaction	1100:1114	the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1100:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	1	65	theme	emerging	237:244	arg1	data					246:249	emerging data	237:249	emerging data	237:249	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	2	66	theme	drug	544:547	arg1	resistance					549:558	drug resistance	544:558	drug resistance	544:558	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	1	67	theme	recent	132:137	arg1	efforts					160:166	recent anti-cancer research efforts	132:166	recent anti-cancer research efforts	132:166	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	7	68	from	effects	1482:1488	arg1	fibroblasts					1505:1515	normal skin fibroblasts	1493:1515	normal skin fibroblasts	1493:1515	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	9	69	theme	siRNA	1661:1665	arg1	experiments					1667:1677	siRNA experiments	1661:1677	siRNA experiments against the respective genes encoding the pyrophosphorylases	1661:1738	siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition.
32028604	1	70	theme	research	151:158	arg1	efforts					160:166	recent anti-cancer research efforts	132:166	recent anti-cancer research efforts	132:166	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	4	71	theme	structure-based	733:747	arg1	screening					757:765	structure-based virtual screening	733:765	structure-based virtual screening	733:765	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	11	72	theme	drug	2169:2172	arg1	candidate					2174:2182	a safe, effective, multi-target anti-cancer drug candidate	2125:2182	a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics	2125:2250	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	10	73	theme	cultured	1949:1956	arg1	cells					1965:1969	cultured cancer cells	1949:1969	cultured cancer cells	1949:1969	Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively.
32028604	2	74	theme	documented	487:496	arg1	roles					498:502	its documented roles	483:502	its documented roles in cancer tumorigenesis, metastasis and drug resistance	483:558	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	11	75	dep	safe	2127:2130	arg1	multi-target					2144:2155	multi-target	2144:2155	multi-target	2144:2155	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	11	75	dep	safe	2127:2130	arg1	effective					2133:2141	effective	2133:2141	effective	2133:2141	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	5	76	theme	GALT	1151:1154	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	76	theme	GALT	1151:1154	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	76	theme	GALT	1151:1154	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	76	theme	GALT	1151:1154	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	8	77	theme	blot	1536:1539	arg1	analysis					1541:1548	Western blot analysis	1528:1548	Western blot analysis	1528:1548	Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells.
32028604	0	78	theme	Inhibitors	19:28	arg1	Discovery					0:8	Discovery	0:8	Discovery of Novel Inhibitors	0:28	Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.
32028604	2	79	theme	cancerous	437:445	arg1	cells					447:451	cancerous cells	437:451	cancerous cells	437:451	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	3	80	theme	glycan	659:664	arg1	synthesis					666:674	glycan synthesis	659:674	glycan synthesis	659:674	We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers.
32028604	4	81	theme	kinetic	771:777	arg1	assay					779:783	kinetic assay	771:783	kinetic assay	771:783	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	0	82	theme	Multi-UDP-hexose	40:55	arg1	Pyrophosphorylases					57:74	Multi-UDP-hexose Pyrophosphorylases	40:74	Multi-UDP-hexose Pyrophosphorylases	40:74	Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.
32028604	0	82	theme	Multi-UDP-hexose	40:55	arg1	Agents					90:95	Anticancer Agents	79:95	Anticancer Agents	79:95	Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.
32028604	10	83	dep	relationships	1863:1875	arg1	cells					1965:1969	cultured cancer cells	1949:1969	cultured cancer cells	1949:1969	Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively.
32028604	11	84	used	used	2199:2202	arg2	candidate					2174:2182	a safe, effective, multi-target anti-cancer drug candidate	2125:2182	a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics	2125:2250	With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.
32028604	2	85	theme	altered	406:412	arg1	processes					424:432	the altered metabolic processes	402:432	the altered metabolic processes in cancerous cells	402:451	In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance.
32028604	5	86	theme	UGP2	1178:1181	arg1	AGX1/UAP1					1209:1217	AGX1/UAP1	1209:1217	AGX1/UAP1	1209:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	86	theme	UGP2	1178:1181	arg1	GALT					1151:1154	GALT	1151:1154	GALT at Trp190 and Ser192	1151:1175	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	86	theme	UGP2	1178:1181	arg1	sites					1142:1146	the binding sites	1130:1146	the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1	1130:1217	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	86	theme	UGP2	1178:1181	arg1	UGP2					1178:1181	UGP2	1178:1181	UGP2 at Gly116 and Lys127	1178:1202	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	5	87	theme	computational	1060:1072	arg1	studies					1082:1088	The computational docking studies	1056:1088	The computational docking studies	1056:1088	The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively.
32028604	9	88	theme	proposed	1798:1805	arg1	roles					1807:1811	the proposed roles	1794:1811	the proposed roles in cancer growth inhibition	1794:1839	siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition.
32028604	8	89	theme	pAKT	1581:1584	arg1	expression					1567:1576	reduced expression	1559:1576	reduced expression of pAKT (Ser473), pAKT (Thr308)	1559:1608	Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells.
32028604	1	90	theme	targeted	343:350	arg1	intervention					352:363	targeted intervention	343:363	targeted intervention	343:363	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	4	91	theme	drug-like	802:810	arg1	fragment					821:828	a drug-like chemical fragment	800:828	a drug-like chemical fragment	800:828	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	4	91	theme	drug-like	802:810	arg1	GAL-012					831:837	GAL-012	831:837	GAL-012	831:837	Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM.
32028604	7	92	theme	normal	1493:1498	arg1	fibroblasts					1505:1515	normal skin fibroblasts	1493:1515	normal skin fibroblasts	1493:1515	Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM.
32028604	9	93	theme	growth	1823:1828	arg1	inhibition					1830:1839	cancer growth inhibition	1816:1839	cancer growth inhibition	1816:1839	siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition.
32028604	1	94	theme	cellular	269:276	arg1	venues					332:337	new venues	328:337	new venues for targeted intervention	328:363	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
32028604	1	94	theme	cellular	269:276	arg1	metabolism					278:287	altered cellular metabolism	261:287	altered cellular metabolism in cancerous cells	261:306	To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention.
34927585	4	0	theme	molecular	492:500	arg1	simulations					511:521	molecular dynamics simulations	492:521	molecular dynamics simulations	492:521	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
34927585	6	1	theme	human	962:966	arg1	ACE2					968:971	recombinant soluble human ACE2	942:971	recombinant soluble human ACE2	942:971	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	0	2	theme	decoy	86:90	arg1	receptor					92:99	soluble SARS-CoV-2 decoy receptor	67:99	soluble SARS-CoV-2 decoy receptor	67:99	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
34927585	6	3	theme	SARS-CoV-2	991:1000	arg1	receptor					1008:1015	a superior SARS-CoV-2 decoy receptor	980:1015	a superior SARS-CoV-2 decoy receptor with promise	980:1028	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	6	4	theme	simultaneous	888:899	arg1	removal					901:907	simultaneous removal	888:907	simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2	888:971	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	5	5	from	effects	800:806	arg1	stability					826:834	structural stability	815:834	structural stability	815:834	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	5	5	from	effects	800:806	arg1	activity					850:857	catalytic activity	840:857	catalytic activity	840:857	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	4	6	theme	complex	589:595	arg1	formation					597:605	Spike-ACE2 complex formation	578:605	Spike-ACE2 complex formation	578:605	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
34927585	5	7	theme	deleterious	788:798	arg1	effects					800:806	notable deleterious effects	780:806	notable deleterious effects on the structural stability and catalytic activity of the protein	780:872	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	6	8	theme	superior	982:989	arg1	receptor					1008:1015	a superior SARS-CoV-2 decoy receptor	980:1015	a superior SARS-CoV-2 decoy receptor with promise	980:1028	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	5	9	theme	ACE2	623:626	arg1	N-glycosylation					628:642	ACE2 N-glycosylation	623:642	ACE2 N-glycosylation	623:642	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	1	10	theme	viral	116:120	arg1	entry					122:126	viral entry	116:126	viral entry	116:126	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	1	11	theme	host	251:254	arg1	cells					256:260	host cells	251:260	host cells	251:260	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	4	12	theme	structural	470:479	arg1	models					481:486	3D structural models	467:486	3D structural models	467:486	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
34927585	5	13	theme	enhanced	710:717	arg1	affinities					727:736	enhanced binding affinities	710:736	enhanced binding affinities	710:736	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	5	14	theme	N-glycosylation	628:642	arg1	Engineering					608:618	Engineering	608:618	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment	608:696	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	3	15	theme	soluble	340:346	arg1	ACE2					354:357	Recombinant soluble human ACE2	328:357	Recombinant soluble human ACE2	328:357	Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19.
34927585	4	16	theme	3D	467:468	arg1	models					481:486	3D structural models	467:486	3D structural models	467:486	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
34927585	5	17	theme	site-directed	647:659	arg1	mutagenesis					661:671	site-directed mutagenesis	647:671	site-directed mutagenesis	647:671	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	2	18	gly	Glycosylation	263:275	arg1	proteins					285:292	both proteins	280:292	both proteins	280:292	Glycosylation of both proteins is critical for this interaction.
34927585	0	19	theme	improved	47:54	arg1	potency					56:62	improved potency	47:62	improved potency as soluble SARS-CoV-2 decoy receptor	47:99	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
34927585	6	20	theme	N-glycans	927:935	arg1	removal					901:907	simultaneous removal	888:907	simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2	888:971	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	5	21	theme	catalytic	840:848	arg1	activity					850:857	catalytic activity	840:857	catalytic activity	840:857	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	5	22	theme	structural	815:824	arg1	stability					826:834	structural stability	815:834	structural stability	815:834	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	1	23	theme	Spike	182:186	arg1	protein					188:194	its Spike protein	178:194	its Spike protein	178:194	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	0	24	theme	Structure-guided	0:15	arg1	glyco-engineering					17:33	Structure-guided glyco-engineering	0:33	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor	0:99	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
34927585	5	25	theme	glycosidase	676:686	arg1	treatment					688:696	glycosidase treatment	676:696	glycosidase treatment	676:696	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	1	26	theme	protein	188:194	arg1	binding					167:173	the binding	163:173	the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells	163:260	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	0	27	theme	ACE2	38:41	arg1	glyco-engineering					17:33	Structure-guided glyco-engineering	0:33	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor	0:99	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
34927585	6	28	theme	COVID-19	1057:1064	arg1	patients					1066:1073	COVID-19 patients	1057:1073	COVID-19 patients	1057:1073	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	5	29	theme	virus	751:755	arg1	neutralization					757:770	virus neutralization	751:770	virus neutralization	751:770	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	3	30	theme	Recombinant	328:338	arg1	ACE2					354:357	Recombinant soluble human ACE2	328:357	Recombinant soluble human ACE2	328:357	Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19.
34927585	4	31	theme	Spike-ACE2	578:587	arg1	formation					597:605	Spike-ACE2 complex formation	578:605	Spike-ACE2 complex formation	578:605	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
34927585	6	32	theme	recombinant	942:952	arg1	ACE2					968:971	recombinant soluble human ACE2	942:971	recombinant soluble human ACE2	942:971	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	6	33	theme	soluble	954:960	arg1	ACE2					968:971	recombinant soluble human ACE2	942:971	recombinant soluble human ACE2	942:971	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	2	34	theme	proteins	285:292	arg1	Glycosylation					263:275	Glycosylation	263:275	Glycosylation of both proteins	263:292	Glycosylation of both proteins is critical for this interaction.
34927585	6	35	theme	decoy	1002:1006	arg1	receptor					1008:1015	a superior SARS-CoV-2 decoy receptor	980:1015	a superior SARS-CoV-2 decoy receptor with promise	980:1028	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	1	36	theme	angiotensin	199:209	arg1	ACE2					232:235	ACE2	232:235	ACE2	232:235	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	1	36	theme	angiotensin	199:209	arg1	enzyme					222:227	angiotensin converting enzyme 2	199:229	angiotensin converting enzyme 2 (ACE2) presented on host cells	199:260	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	3	37	theme	clinical	413:420	arg1	tests					422:426	clinical tests	413:426	clinical tests for the treatment of COVID-19	413:456	Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19.
34927585	1	38	theme	converting	211:220	arg1	ACE2					232:235	ACE2	232:235	ACE2	232:235	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	1	38	theme	converting	211:220	arg1	enzyme					222:227	angiotensin converting enzyme 2	199:229	angiotensin converting enzyme 2 (ACE2) presented on host cells	199:260	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	3	39	theme	COVID-19	449:456	arg1	treatment					436:444	the treatment	432:444	the treatment of COVID-19	432:456	Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19.
34927585	6	40	theme	effective	1033:1041	arg1	treatment					1043:1051	effective treatment	1033:1051	effective treatment for COVID-19 patients	1033:1073	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	5	41	theme	notable	780:786	arg1	effects					800:806	notable deleterious effects	780:806	notable deleterious effects on the structural stability and catalytic activity of the protein	780:872	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	3	42	theme	human	348:352	arg1	ACE2					354:357	Recombinant soluble human ACE2	328:357	Recombinant soluble human ACE2	328:357	Recombinant soluble human ACE2 can neutralize SARS-CoV-2 and is currently undergoing clinical tests for the treatment of COVID-19.
34927585	6	43	from	ACE2	968:971	arg1	removal					901:907	simultaneous removal	888:907	simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2	888:971	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	5	44	theme	binding	719:725	arg1	affinities					727:736	enhanced binding affinities	710:736	enhanced binding affinities	710:736	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	0	45	theme	soluble	67:73	arg1	receptor					92:99	soluble SARS-CoV-2 decoy receptor	67:99	soluble SARS-CoV-2 decoy receptor	67:99	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
34927585	5	46	theme	protein	866:872	arg1	stability					826:834	structural stability	815:834	structural stability	815:834	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	5	46	theme	protein	866:872	arg1	activity					850:857	catalytic activity	840:857	catalytic activity	840:857	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	6	47	theme	accessible	916:925	arg1	N-glycans					927:935	all accessible N-glycans	912:935	all accessible N-glycans	912:935	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	5	48	dep	stability	826:834	arg1	the					811:813	the	811:813	the	811:813	Engineering of ACE2 N-glycosylation by site-directed mutagenesis or glycosidase treatment resulted in enhanced binding affinities and improved virus neutralization without notable deleterious effects on the structural stability and catalytic activity of the protein.
34927585	4	49	theme	ACE2	537:540	arg1	N-glycans					542:550	the ACE2 N-glycans	533:550	the ACE2 N-glycans that critically influence Spike-ACE2 complex formation	533:605	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
34927585	1	50	theme	SARS-CoV-2	131:140	arg1	Infection					102:110	Infection	102:110	Infection	102:110	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	1	50	theme	SARS-CoV-2	131:140	arg1	entry					122:126	viral entry	116:126	viral entry	116:126	Infection and viral entry of SARS-CoV-2 crucially depends on the binding of its Spike protein to angiotensin converting enzyme 2 (ACE2) presented on host cells.
34927585	6	51	with	receptor	1008:1015	arg1	promise					1022:1028	promise	1022:1028	promise	1022:1028	Importantly, simultaneous removal of all accessible N-glycans from recombinant soluble human ACE2 yields a superior SARS-CoV-2 decoy receptor with promise as effective treatment for COVID-19 patients.
34927585	0	52	theme	SARS-CoV-2	75:84	arg1	receptor					92:99	soluble SARS-CoV-2 decoy receptor	67:99	soluble SARS-CoV-2 decoy receptor	67:99	Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor.
34927585	4	53	used	used	462:465	arg2	We					459:460	We	459:460	We	459:460	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
34927585	4	54	theme	dynamics	502:509	arg1	simulations					511:521	molecular dynamics simulations	492:521	molecular dynamics simulations	492:521	We used 3D structural models and molecular dynamics simulations to define the ACE2 N-glycans that critically influence Spike-ACE2 complex formation.
33277506	0	0	theme	efficient	72:80	arg1	transfucosylation					86:102	highly efficient IgG transfucosylation	65:102	highly efficient IgG transfucosylation	65:102	Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation.
33277506	6	1	theme	transfucosylation	916:932	arg1	experiments					934:944	transfucosylation experiments	916:944	transfucosylation experiments	916:944	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	1	2	theme	many	151:154	arg1	proteins					156:163	many proteins	151:163	many proteins with biotechnical and medical applications	151:206	Fucosylation is important for the function of many proteins with biotechnical and medical applications.
33277506	7	3	theme	transfucosidase	1502:1516	arg1	mutants					1518:1524	AlfC transfucosidase mutants	1497:1524	AlfC transfucosidase mutants	1497:1524	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	1	4	with	proteins	156:163	arg1	applications					195:206	biotechnical and medical applications	170:206	biotechnical and medical applications	170:206	Fucosylation is important for the function of many proteins with biotechnical and medical applications.
33277506	6	5	theme	mutational	801:810	arg1	analyses					824:831	mutational and kinetic analyses	801:831	mutational and kinetic analyses	801:831	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	1	6	theme	proteins	156:163	arg1	function					139:146	the function	135:146	the function of many proteins with biotechnical and medical applications	135:206	Fucosylation is important for the function of many proteins with biotechnical and medical applications.
33277506	7	7	theme	enzymatic	1198:1206	arg1	activity					1208:1215	enzymatic activity	1198:1215	enzymatic activity	1198:1215	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	4	8	theme	point	516:520	arg1	mutants					522:528	certain point mutants	508:528	certain point mutants thereof	508:536	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	4	9	theme	antibody	594:601	arg1	N-glycans					603:611	monoclonal antibody N-glycans	583:611	monoclonal antibody N-glycans	583:611	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	0	10	theme	IgG	82:84	arg1	transfucosylation					86:102	highly efficient IgG transfucosylation	65:102	highly efficient IgG transfucosylation	65:102	Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation.
33277506	7	11	theme	open	1243:1246	arg1	conformations					1259:1271	distinct open and closed conformations	1234:1271	distinct open and closed conformations of an active-site loop	1234:1294	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	4	12	theme	monoclonal	583:592	arg1	N-glycans					603:611	monoclonal antibody N-glycans	583:611	monoclonal antibody N-glycans	583:611	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	5	13	dep	potential	680:688	arg1	uses					690:693	uses	690:693	uses	690:693	Despite the potential uses for AlfC, little is known about its mechanism.
33277506	6	14	theme	dynamic	891:897	arg1	simulations					899:909	molecular dynamic simulations	881:909	molecular dynamic simulations	881:909	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	3	15	located	found	456:460	arg2	-fucose					430:436	α(1,6)-fucose	424:436	α(1,6)-fucose	424:436	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	3	15	located	found	456:460	arg2	linkage					448:454	the only linkage	439:454	the only linkage found in human N-glycan core fucosylation	439:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	3	15	located	found	456:460	arg1	fucosylation					485:496	human N-glycan core fucosylation	465:496	human N-glycan core fucosylation	465:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	2	16	theme	diverse	302:308	arg1	α-linkages					310:319	diverse α-linkages	302:319	diverse α-linkages on these proteins	302:337	Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.
33277506	3	17	theme	only	443:446	arg1	linkage					448:454	the only linkage	439:454	the only linkage found in human N-glycan core fucosylation	439:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	3	17	theme	only	443:446	arg1	-fucose					430:436	α(1,6)-fucose	424:436	α(1,6)-fucose	424:436	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	6	18	theme	molecular	881:889	arg1	simulations					899:909	molecular dynamic simulations	881:909	molecular dynamic simulations	881:909	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	4	19	used	used	548:551	arg2	mutants					522:528	certain point mutants	508:528	certain point mutants thereof	508:536	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	4	19	used	used	548:551	arg2	AlfC					499:502	AlfC	499:502	AlfC	499:502	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	6	20	theme	AlfC	781:784	arg1	structures					767:776	crystal structures	759:776	crystal structures	759:776	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	1	21	theme	biotechnical	170:181	arg1	applications					195:206	biotechnical and medical applications	170:206	biotechnical and medical applications	170:206	Fucosylation is important for the function of many proteins with biotechnical and medical applications.
33277506	2	22	gly	fucosylated	274:284	arg1	substrates					286:295	fucosylated substrates	274:295	fucosylated substrates	274:295	Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.
33277506	7	23	theme	adjacent	1099:1106	arg1	subsite					1091:1097	an aromatic subsite	1079:1097	an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages	1079:1182	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	24	theme	AlfC	1497:1500	arg1	mutants					1518:1524	AlfC transfucosidase mutants	1497:1524	AlfC transfucosidase mutants	1497:1524	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	3	25	theme	α	424:424	arg1	linkage					448:454	the only linkage	439:454	the only linkage found in human N-glycan core fucosylation	439:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	3	25	theme	α	424:424	arg1	-fucose					430:436	α(1,6)-fucose	424:436	α(1,6)-fucose	424:436	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	6	26	theme	activities	988:997	arg1	mechanisms					970:979	the molecular mechanisms	956:979	the molecular mechanisms of the activities of AlfC and its transfucosidase mutants	956:1037	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	1	27	theme	medical	187:193	arg1	applications					195:206	biotechnical and medical applications	170:206	biotechnical and medical applications	170:206	Fucosylation is important for the function of many proteins with biotechnical and medical applications.
33277506	7	28	theme	aromatic	1082:1089	arg1	subsite					1091:1097	an aromatic subsite	1079:1097	an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages	1079:1182	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	6	29	theme	crystal	759:765	arg1	structures					767:776	crystal structures	759:776	crystal structures	759:776	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	7	30	theme	active	1115:1120	arg1	site					1122:1125	the active site	1111:1125	the active site that specifically accommodates GlcNAc in α(1,6)-linkages	1111:1182	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	3	31	theme	human	465:469	arg1	fucosylation					485:496	human N-glycan core fucosylation	465:496	human N-glycan core fucosylation	465:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	6	32	theme	mutants	1031:1037	arg1	activities					988:997	the activities	984:997	the activities of AlfC and its transfucosidase mutants	984:1037	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	3	33	theme	N-glycan	471:478	arg1	fucosylation					485:496	human N-glycan core fucosylation	465:496	human N-glycan core fucosylation	465:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	0	34	theme	α-fucosidase	29:40	arg1	dynamics					14:21	dynamics	14:21	dynamics	14:21	Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation.
33277506	0	34	theme	α-fucosidase	29:40	arg1	Structure					0:8	Structure	0:8	Structure	0:8	Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation.
33277506	6	35	theme	mass	862:865	arg1	spectrometry					867:878	hydrogen-deuterium exchange mass spectrometry	834:878	hydrogen-deuterium exchange mass spectrometry	834:878	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	4	36	from	impacts	631:637	arg1	functions					657:665	their effector functions	642:665	their effector functions	642:665	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	4	37	theme	effector	648:655	arg1	functions					657:665	their effector functions	642:665	their effector functions	642:665	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	6	38	theme	molecular	960:968	arg1	mechanisms					970:979	the molecular mechanisms	956:979	the molecular mechanisms of the activities of AlfC and its transfucosidase mutants	956:1037	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	6	39	theme	exchange	853:860	arg1	spectrometry					867:878	hydrogen-deuterium exchange mass spectrometry	834:878	hydrogen-deuterium exchange mass spectrometry	834:878	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	2	40	theme	enzyme	244:249	arg1	family					251:256	a large enzyme family	236:256	a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins	236:337	Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.
33277506	6	41	theme	hydrogen-deuterium	834:851	arg1	spectrometry					867:878	hydrogen-deuterium exchange mass spectrometry	834:878	hydrogen-deuterium exchange mass spectrometry	834:878	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	2	42	theme	large	238:242	arg1	family					251:256	a large enzyme family	236:256	a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins	236:337	Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.
33277506	7	43	theme	rational	1476:1483	arg1	creation					1485:1492	the rational creation	1472:1492	the rational creation of AlfC transfucosidase mutants	1472:1524	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	44	theme	active-site	1279:1289	arg1	loop					1291:1294	an active-site loop	1276:1294	an active-site loop	1276:1294	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	3	45	theme	1,6	426:428	arg1	linkage					448:454	the only linkage	439:454	the only linkage found in human N-glycan core fucosylation	439:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	3	45	theme	1,6	426:428	arg1	-fucose					430:436	α(1,6)-fucose	424:436	α(1,6)-fucose	424:436	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	4	46	with	N-glycans	603:611	arg1	impacts					631:637	significant impacts	619:637	significant impacts on their effector functions	619:665	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	7	47	theme	loop	1291:1294	arg1	conformations					1259:1271	distinct open and closed conformations	1234:1271	distinct open and closed conformations of an active-site loop	1234:1294	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	48	theme	mutants	1518:1524	arg1	creation					1485:1492	the rational creation	1472:1492	the rational creation of AlfC transfucosidase mutants	1472:1524	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	49	theme	generalizable	1444:1456	arg1	framework					1458:1466	a potentially generalizable framework	1430:1466	a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants	1430:1524	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	3	50	theme	core	480:483	arg1	fucosylation					485:496	human N-glycan core fucosylation	465:496	human N-glycan core fucosylation	465:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	6	51	theme	kinetic	816:822	arg1	analyses					824:831	mutational and kinetic analyses	801:831	mutational and kinetic analyses	801:831	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	2	52	theme	fucosylated	274:284	arg1	substrates					286:295	fucosylated substrates	274:295	fucosylated substrates	274:295	Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.
33277506	7	53	dep	conformations	1358:1370	arg1	promote					1375:1381	promote	1375:1381	to promote transfucosylation over hydrolysis	1372:1415	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	54	theme	distinct	1234:1241	arg1	conformations					1259:1271	distinct open and closed conformations	1234:1271	distinct open and closed conformations of an active-site loop	1234:1294	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	55	theme	open	1353:1356	arg1	conformations					1358:1370	open conformations	1353:1370	open conformations to promote transfucosylation over hydrolysis	1353:1415	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	56	theme	certain	1302:1308	arg1	mutations					1310:1318	certain mutations	1302:1318	certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis	1302:1415	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	7	57	theme	closed	1252:1257	arg1	conformations					1259:1271	distinct open and closed conformations	1234:1271	distinct open and closed conformations of an active-site loop	1234:1294	Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
33277506	2	58	from	α-linkages	310:319	arg1	proteins					330:337	these proteins	324:337	these proteins	324:337	Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.
33277506	4	59	theme	significant	619:629	arg1	impacts					631:637	significant impacts	619:637	significant impacts on their effector functions	619:665	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	6	60	theme	AlfC	1002:1005	arg1	activities					988:997	the activities	984:997	the activities of AlfC and its transfucosidase mutants	984:1037	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
33277506	4	61	theme	certain	508:514	arg1	mutants					522:528	certain point mutants	508:528	certain point mutants thereof	508:536	AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibody N-glycans, with significant impacts on their effector functions.
33277506	3	62	with	α-fucosidase	372:383	arg1	specificity					404:414	specificity	404:414	specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation	404:496	Lactobacillus casei produces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in human N-glycan core fucosylation.
33277506	6	63	theme	transfucosidase	1015:1029	arg1	mutants					1031:1037	its transfucosidase mutants	1011:1037	its transfucosidase mutants	1011:1037	Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen-deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants.
34241943	1	0	theme	host	198:201	arg1	machinery					203:211	the host machinery	194:211	the host machinery	194:211	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34241943	0	1	theme	Mimivirus	76:84	arg1	Case					68:71	The Case	64:71	The Case of Mimivirus	64:84	Expanding the Occurrence of Polysaccharides to the Viral World: The Case of Mimivirus.
34241943	5	2	theme	viral	1067:1071	arg1	glycobiology					1073:1084	viral glycobiology	1067:1084	viral glycobiology	1067:1084	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	3	3	theme	autonomous	484:493	arg1	machinery					509:517	an autonomous glycosylation machinery	481:517	an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts	481:669	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	5	4	theme	opening	1031:1037	arg1	avenues					1043:1049	the cellular world and opening new avenues	1008:1049	avenues	1043:1049	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	5	5	from	absent	939:944	arg1	viruses					949:955	viruses	949:955	viruses	949:955	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	3	6	theme	viral	652:656	arg1	counterparts					658:669	the viral counterparts	648:669	the viral counterparts	648:669	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	5	7	theme	such	915:918	arg1	macromolecules					920:933	such macromolecules	915:933	such macromolecules	915:933	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	3	8	from	size	561:564	arg1	similar					550:556	similar	550:556	similar	550:556	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	5	9	from	avenues	1043:1049	arg1	field					1058:1062	the field	1054:1062	the field of viral glycobiology	1054:1084	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	3	10	theme	glycosylation	495:507	arg1	machinery					509:517	an autonomous glycosylation machinery	481:517	an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts	481:669	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	5	11	theme	new	1039:1041	arg1	avenues					1043:1049	the cellular world and opening new avenues	1008:1049	avenues	1043:1049	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	3	12	dep	similar	550:556	arg1	albeit					606:611	albeit	606:611	albeit	606:611	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	3	12	dep	similar	550:556	arg1	different					613:621	different	613:621	different	613:621	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	4	13	theme	discrete	855:862	arg1	size					864:867	discrete size	855:867	discrete size	855:867	We report herein that Mimivirus possesses a glycocalyx made of two different polysaccharides, now challenging the concept that all viruses coat their capsids with oligosaccharides of discrete size.
34241943	1	14	theme	size	156:159	arg1	terms					147:151	terms	147:151	terms of size and genome	147:170	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34241943	2	15	theme	Giant	242:246	arg1	viruses					248:254	Giant viruses	242:254	Giant viruses	242:254	Giant viruses subvert all these concepts: their particles are not small, and their genome is more complex than that of some bacteria.
34241943	5	16	from	viruses	949:955	arg1	absent					939:944	absent	939:944	absent	939:944	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	5	17	theme	cellular	1012:1019	arg1	world					1021:1025	the cellular world and opening new avenues	1008:1049	world	1021:1025	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	4	18	theme	different	739:747	arg1	polysaccharides					749:763	two different polysaccharides	735:763	two different polysaccharides	735:763	We report herein that Mimivirus possesses a glycocalyx made of two different polysaccharides, now challenging the concept that all viruses coat their capsids with oligosaccharides of discrete size.
34241943	3	19	from	similar	550:556	arg1	size					561:564	size	561:564	size	561:564	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	3	19	from	similar	550:556	arg1	structure					626:634	structure	626:634	structure	626:634	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	1	20	theme	genome	165:170	arg1	terms					147:151	terms	147:151	terms of size and genome	147:170	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34241943	0	21	theme	Polysaccharides	28:42	arg1	Occurrence					14:23	the Occurrence	10:23	the Occurrence of Polysaccharides to the Viral World	10:61	Expanding the Occurrence of Polysaccharides to the Viral World: The Case of Mimivirus.
34241943	5	22	theme	glycobiology	1073:1084	arg1	field					1058:1062	the field	1054:1062	the field of viral glycobiology	1054:1084	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	4	23	theme	size	864:867	arg1	oligosaccharides					835:850	oligosaccharides	835:850	oligosaccharides of discrete size	835:867	We report herein that Mimivirus possesses a glycocalyx made of two different polysaccharides, now challenging the concept that all viruses coat their capsids with oligosaccharides of discrete size.
34241943	3	24	theme	similar	550:556	arg1	oligosaccharides					533:548	oligosaccharides	533:548	oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts	533:669	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	0	25	theme	Viral	51:55	arg1	World					57:61	the Viral World	47:61	the Viral World	47:61	Expanding the Occurrence of Polysaccharides to the Viral World: The Case of Mimivirus.
34241943	4	26	contain	possesses	704:712	arg1	Mimivirus					694:702	Mimivirus	694:702	Mimivirus	694:702	We report herein that Mimivirus possesses a glycocalyx made of two different polysaccharides, now challenging the concept that all viruses coat their capsids with oligosaccharides of discrete size.
34241943	4	26	contain	possesses	704:712	arg2	glycocalyx					716:725	a glycocalyx	714:725	a glycocalyx made of two different polysaccharides	714:763	We report herein that Mimivirus possesses a glycocalyx made of two different polysaccharides, now challenging the concept that all viruses coat their capsids with oligosaccharides of discrete size.
34241943	5	27	from	world	1021:1025	arg1	field					1058:1062	the field	1054:1062	the field of viral glycobiology	1054:1084	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	3	28	theme	small	578:582	arg1	viruses					584:590	small viruses	578:590	small viruses (6-12 units)	578:603	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	3	28	theme	small	578:582	arg1	units					598:602	6-12 units	593:602	6-12 units	593:602	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	1	29	gly	glycosylate	216:226	arg1	capsid					234:239	their capsid	228:239	their capsid	228:239	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34241943	1	30	theme	general	91:97	arg1	perception					99:108	The general perception	87:108	The general perception of viruses	87:119	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34241943	3	31	from	structure	626:634	arg1	similar					550:556	similar	550:556	similar	550:556	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	3	32	contain	have	476:479	arg1	Chloroviruses					462:474	Chloroviruses	462:474	Chloroviruses	462:474	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	3	32	contain	have	476:479	arg2	machinery					509:517	an autonomous glycosylation machinery	481:517	an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts	481:669	Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts.
34241943	4	33	with	coat	811:814	arg1	oligosaccharides					835:850	oligosaccharides	835:850	oligosaccharides of discrete size	835:867	We report herein that Mimivirus possesses a glycocalyx made of two different polysaccharides, now challenging the concept that all viruses coat their capsids with oligosaccharides of discrete size.
34241943	5	34	theme	giant	990:994	arg1	viruses					996:1002	giant viruses	990:1002	giant viruses	990:1002	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	5	35	dep	paradigm	901:908	arg1	absent					939:944	absent	939:944	absent	939:944	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	1	36	from	terms	147:151	arg1	small					138:142	small	138:142	small	138:142	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34241943	1	37	theme	viruses	113:119	arg1	perception					99:108	The general perception	87:108	The general perception of viruses	87:119	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34241943	5	38	from	viruses	996:1002	arg1	field					1058:1062	the field	1054:1062	the field of viral glycobiology	1054:1084	This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.
34241943	0	39	dep	Expanding	0:8	arg1	Case					68:71	The Case	64:71	The Case of Mimivirus	64:84	Expanding the Occurrence of Polysaccharides to the Viral World: The Case of Mimivirus.
34241943	1	40	from	small	138:142	arg1	terms					147:151	terms	147:151	terms of size and genome	147:170	The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid.
34010560	4	0	from	interpretation	840:853	arg1	data					898:901	glycoproteomic data	883:901	glycoproteomic data	883:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	3	1	theme	backbone	769:776	arg1	cleavages					724:732	the cleavages	720:732	the cleavages of both the glycan and the peptide backbone	720:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	2	2	gly	glycosylation	448:460	arg1	throughput					470:479	high throughput	465:479	high throughput in complex glycoproteomic samples	465:513	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	1	3	theme	common	168:173	arg1	PTM					209:211	PTM	209:211	PTM	209:211	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	3	theme	common	168:173	arg1	modifications					194:206	the most common post-translational modifications	159:206	the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms	159:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	4	theme	important	260:268	arg1	functions					281:289	important biological functions	260:289	important biological functions in human and other higher organisms	260:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	0	5	theme	Collision	103:111	arg1	EThcD					127:131	EThcD	127:131	EThcD	127:131	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	0	5	theme	Collision	103:111	arg1	Dissociation					113:124	Electron Transfer/High-Energy Collision Dissociation	73:124	Electron Transfer/High-Energy Collision Dissociation (EThcD)	73:132	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	1	6	theme	post-translational	175:192	arg1	PTM					209:211	PTM	209:211	PTM	209:211	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	6	theme	post-translational	175:192	arg1	modifications					194:206	the most common post-translational modifications	159:206	the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms	159:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	7	theme	biological	270:279	arg1	functions					281:289	important biological functions	260:289	important biological functions in human and other higher organisms	260:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	6	8	theme	better	1224:1229	arg1	performance					1231:1241	comparable or better performance	1210:1241	comparable or better performance	1210:1241	The results showed that it achieved comparable or better performance than that of Byonic and MSFragger.
34010560	4	9	theme	EThcD-MS/MS	858:868	arg1	spectra					870:876	EThcD-MS/MS spectra	858:876	EThcD-MS/MS spectra from glycoproteomic data	858:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	7	10	used	used	1351:1354	arg2	software					1323:1330	an open source software	1308:1330	an open source software	1308:1330	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	7	10	used	used	1351:1354	arg2	GlycoHybridSeq					1278:1291	GlycoHybridSeq	1278:1291	GlycoHybridSeq	1278:1291	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	4	11	theme	customized	911:920	arg1	function					930:937	a customized scoring function	909:937	a customized scoring function	909:937	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	4	12	theme	automated	830:838	arg1	interpretation					840:853	automated interpretation	830:853	automated interpretation of EThcD-MS/MS spectra from glycoproteomic data	830:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	5	13	theme	glycoproteomic	1112:1125	arg1	data					1127:1130	glycoproteomic data	1112:1130	glycoproteomic data collected for cancer biomarker discovery	1112:1171	We evaluate GlycoHybridSeq on glycoproteomic data collected for cancer biomarker discovery.
34010560	4	14	theme	isomeric	1064:1071	arg1	glycans					1073:1079	some isomeric glycans	1059:1079	some isomeric glycans	1059:1079	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	7	15	theme	large-scale	1359:1369	arg1	analyses					1391:1398	large-scale glycoproteomic data analyses	1359:1398	large-scale glycoproteomic data analyses	1359:1398	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	3	16	theme	glycopeptide	606:617	arg1	identification					619:632	glycopeptide identification	606:632	glycopeptide identification	606:632	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	3	17	theme	electron	526:533	arg1	EThcD					580:584	EThcD	580:584	EThcD	580:584	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	3	17	theme	electron	526:533	arg1	dissociation					566:577	electron transfer/high-energy collision dissociation	526:577	electron transfer/high-energy collision dissociation (EThcD)	526:585	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	7	18	theme	source	1316:1321	arg1	GlycoHybridSeq					1278:1291	GlycoHybridSeq	1278:1291	GlycoHybridSeq	1278:1291	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	7	18	theme	source	1316:1321	arg1	software					1323:1330	an open source software	1308:1330	an open source software	1308:1330	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	4	19	gly	glycosylation	1019:1031	arg2	sites					1033:1037	glycosylation sites	1019:1037	glycosylation sites	1019:1037	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	1	20	theme	modifications	194:206	arg1	one					152:154	one	152:154	one	152:154	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	20	theme	modifications	194:206	arg1	PTM					209:211	PTM	209:211	PTM	209:211	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	20	theme	modifications	194:206	arg1	modifications					194:206	the most common post-translational modifications	159:206	the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms	159:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	2	21	theme	glycoproteomic	492:505	arg1	samples					507:513	complex glycoproteomic samples	484:513	complex glycoproteomic samples	484:513	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	4	22	theme	scoring	922:928	arg1	function					930:937	a customized scoring function	909:937	a customized scoring function	909:937	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	7	23	theme	open	1311:1314	arg1	GlycoHybridSeq					1278:1291	GlycoHybridSeq	1278:1291	GlycoHybridSeq	1278:1291	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	7	23	theme	open	1311:1314	arg1	software					1323:1330	an open source software	1308:1330	an open source software	1308:1330	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	2	24	theme	complex	484:490	arg1	samples					507:513	complex glycoproteomic samples	484:513	complex glycoproteomic samples	484:513	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	3	25	with	glycopepides	679:690	arg1	ions					710:713	the fragment ions	697:713	the fragment ions from the cleavages of both the glycan and the peptide backbone	697:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	2	26	theme	chromatography	335:348	arg1	spectrometry					362:373	Liquid chromatography tandem mass spectrometry	328:373	Liquid chromatography tandem mass spectrometry (LC-MS/MS)	328:384	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	2	26	theme	chromatography	335:348	arg1	LC-MS/MS					376:383	LC-MS/MS	376:383	LC-MS/MS	376:383	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	3	27	from	cleavages	724:732	arg1	ions					710:713	the fragment ions	697:713	the fragment ions from the cleavages of both the glycan and the peptide backbone	697:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	2	28	theme	Liquid	328:333	arg1	spectrometry					362:373	Liquid chromatography tandem mass spectrometry	328:373	Liquid chromatography tandem mass spectrometry (LC-MS/MS)	328:384	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	2	28	theme	Liquid	328:333	arg1	LC-MS/MS					376:383	LC-MS/MS	376:383	LC-MS/MS	376:383	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	1	29	from	functions	281:289	arg1	human					294:298	human	294:298	human	294:298	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	29	from	functions	281:289	arg1	organisms					317:325	other higher organisms	304:325	other higher organisms	304:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	0	30	theme	Automated	16:24	arg1	Identification					26:39	Automated Identification	16:39	Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD)	16:132	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	1	31	theme	other	304:308	arg1	organisms					317:325	other higher organisms	304:325	other higher organisms	304:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	4	32	theme	glycosylation	1019:1031	arg1	sites					1033:1037	glycosylation sites	1019:1037	glycosylation sites	1019:1037	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	4	33	theme	software	802:809	arg1	GlycoHybridSeq					811:824	the software GlycoHybridSeq	798:824	the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data	798:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	3	34	from	information	664:674	arg1	glycopepides					679:690	glycopepides	679:690	glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone	679:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	7	35	theme	glycoproteomic	1371:1384	arg1	analyses					1391:1398	large-scale glycoproteomic data analyses	1359:1398	large-scale glycoproteomic data analyses	1359:1398	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	0	36	theme	N-Linked	44:51	arg1	Glycopeptides					53:65	N-Linked Glycopeptides	44:65	N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD)	44:132	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	1	37	theme	higher	310:315	arg1	organisms					317:325	other higher organisms	304:325	other higher organisms	304:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	2	38	theme	protein	440:446	arg1	glycosylation					448:460	site-specific protein glycosylation	426:460	site-specific protein glycosylation	426:460	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	6	39	theme	comparable	1210:1219	arg1	performance					1231:1241	comparable or better performance	1210:1241	comparable or better performance	1210:1241	The results showed that it achieved comparable or better performance than that of Byonic and MSFragger.
34010560	5	40	theme	cancer	1146:1151	arg1	discovery					1163:1171	cancer biomarker discovery	1146:1171	cancer biomarker discovery	1146:1171	We evaluate GlycoHybridSeq on glycoproteomic data collected for cancer biomarker discovery.
34010560	1	41	theme	large	229:233	arg1	proteins					246:253	proteins	246:253	proteins with important biological functions in human and other higher organisms	246:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	41	theme	large	229:233	arg1	variety					235:241	a large variety	227:241	a large variety of proteins with important biological functions in human and other higher organisms	227:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	3	42	theme	rich	648:651	arg1	information					664:674	rich structural information	648:674	rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone	648:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	3	43	theme	transfer/high-energy	535:554	arg1	EThcD					580:584	EThcD	580:584	EThcD	580:584	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	3	43	theme	transfer/high-energy	535:554	arg1	dissociation					566:577	electron transfer/high-energy collision dissociation	526:577	electron transfer/high-energy collision dissociation (EThcD)	526:585	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	0	44	theme	Glycopeptides	53:65	arg1	Identification					26:39	Automated Identification	16:39	Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD)	16:132	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	3	45	theme	peptide	761:767	arg1	backbone					769:776	the peptide backbone	757:776	the peptide backbone	757:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	3	46	theme	structural	653:662	arg1	information					664:674	rich structural information	648:674	rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone	648:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	3	47	theme	collision	556:564	arg1	EThcD					580:584	EThcD	580:584	EThcD	580:584	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	3	47	theme	collision	556:564	arg1	dissociation					566:577	electron transfer/high-energy collision dissociation	526:577	electron transfer/high-energy collision dissociation (EThcD)	526:585	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	7	48	theme	data	1386:1389	arg1	analyses					1391:1398	large-scale glycoproteomic data analyses	1359:1398	large-scale glycoproteomic data analyses	1359:1398	GlycoHybridSeq is released as an open source software and is ready to be used in large-scale glycoproteomic data analyses.
34010560	3	49	theme	glycan	746:751	arg1	cleavages					724:732	the cleavages	720:732	the cleavages of both the glycan and the peptide backbone	720:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	0	50	dep	Identification	26:39	arg1	GlycoHybridSeq					0:13	GlycoHybridSeq	0:13	GlycoHybridSeq	0:13	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	4	51	from	data	898:901	arg1	interpretation					840:853	automated interpretation	830:853	automated interpretation of EThcD-MS/MS spectra from glycoproteomic data	830:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	4	51	from	data	898:901	arg1	spectra					870:876	EThcD-MS/MS spectra	858:876	EThcD-MS/MS spectra from glycoproteomic data	858:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	2	52	theme	mass	357:360	arg1	spectrometry					362:373	Liquid chromatography tandem mass spectrometry	328:373	Liquid chromatography tandem mass spectrometry (LC-MS/MS)	328:384	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	2	52	theme	mass	357:360	arg1	LC-MS/MS					376:383	LC-MS/MS	376:383	LC-MS/MS	376:383	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	5	53	theme	biomarker	1153:1161	arg1	discovery					1163:1171	cancer biomarker discovery	1146:1171	cancer biomarker discovery	1146:1171	We evaluate GlycoHybridSeq on glycoproteomic data collected for cancer biomarker discovery.
34010560	3	54	theme	fragment	701:708	arg1	ions					710:713	the fragment ions	697:713	the fragment ions from the cleavages of both the glycan and the peptide backbone	697:776	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	1	55	with	proteins	246:253	arg1	functions					281:289	important biological functions	260:289	important biological functions in human and other higher organisms	260:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	2	56	theme	tandem	350:355	arg1	spectrometry					362:373	Liquid chromatography tandem mass spectrometry	328:373	Liquid chromatography tandem mass spectrometry (LC-MS/MS)	328:384	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	2	56	theme	tandem	350:355	arg1	LC-MS/MS					376:383	LC-MS/MS	376:383	LC-MS/MS	376:383	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	4	57	theme	spectra	870:876	arg1	interpretation					840:853	automated interpretation	830:853	automated interpretation of EThcD-MS/MS spectra from glycoproteomic data	830:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	0	58	theme	Transfer/High-Energy	82:101	arg1	EThcD					127:131	EThcD	127:131	EThcD	127:131	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	0	58	theme	Transfer/High-Energy	82:101	arg1	Dissociation					113:124	Electron Transfer/High-Energy Collision Dissociation	73:124	Electron Transfer/High-Energy Collision Dissociation (EThcD)	73:132	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	2	59	theme	site-specific	426:438	arg1	glycosylation					448:460	site-specific protein glycosylation	426:460	site-specific protein glycosylation	426:460	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	4	60	theme	glycoproteomic	883:896	arg1	data					898:901	glycoproteomic data	883:901	glycoproteomic data	883:901	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
34010560	2	61	used	used	405:408	arg2	LC-MS/MS					376:383	LC-MS/MS	376:383	LC-MS/MS	376:383	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	2	61	used	used	405:408	arg2	spectrometry					362:373	Liquid chromatography tandem mass spectrometry	328:373	Liquid chromatography tandem mass spectrometry (LC-MS/MS)	328:384	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	3	62	gly	glycopeptide	606:617	arg2	glycopeptide					606:617	glycopeptide identification	606:632	glycopeptide identification	606:632	Recently, electron transfer/high-energy collision dissociation (EThcD) was introduced for glycopeptide identification, which offers rich structural information on glycopepides with the fragment ions from the cleavages of both the glycan and the peptide backbone.
34010560	1	63	theme	proteins	246:253	arg1	proteins					246:253	proteins	246:253	proteins with important biological functions in human and other higher organisms	246:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	1	63	theme	proteins	246:253	arg1	variety					235:241	a large variety	227:241	a large variety of proteins with important biological functions in human and other higher organisms	227:325	Glycosylation is one of the most common post-translational modifications (PTM) occurring in a large variety of proteins with important biological functions in human and other higher organisms.
34010560	0	64	theme	Electron	73:80	arg1	EThcD					127:131	EThcD	127:131	EThcD	127:131	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	0	64	theme	Electron	73:80	arg1	Dissociation					113:124	Electron Transfer/High-Energy Collision Dissociation	73:124	Electron Transfer/High-Energy Collision Dissociation (EThcD)	73:132	GlycoHybridSeq: Automated Identification of N-Linked Glycopeptides Using Electron Transfer/High-Energy Collision Dissociation (EThcD).
34010560	2	65	from	throughput	470:479	arg1	samples					507:513	complex glycoproteomic samples	484:513	complex glycoproteomic samples	484:513	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	2	66	theme	high	465:468	arg1	throughput					470:479	high throughput	465:479	high throughput in complex glycoproteomic samples	465:513	Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been routinely used to characterize site-specific protein glycosylation at high throughput in complex glycoproteomic samples.
34010560	4	67	gly	glycopeptides	989:1001	arg2	glycopeptides					989:1001	glycopeptides	989:1001	glycopeptides	989:1001	Herein, we present the software GlycoHybridSeq for automated interpretation of EThcD-MS/MS spectra from glycoproteomic data using a customized scoring function, which enables the functionalities of identifying glycopeptides, characterizing glycosylation sites, and distinguishing some isomeric glycans.
33908016	3	0	used	used	691:694	arg2	derivatization					669:682	Sialic acid chemical derivatization	648:682	Sialic acid chemical derivatization	648:682	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	0	1	dep	Formalin-Fixed	137:150	arg1	Paraffin-Embedded					153:169	Paraffin-Embedded	153:169	Paraffin-Embedded	153:169	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	1	2	theme	matrix-assisted	274:288	arg1	IMS					353:355	IMS	353:355	IMS	353:355	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	2	theme	matrix-assisted	274:288	arg1	spectrometry					339:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry	274:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	274:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	0	3	theme	Isomer	88:93	arg1	Detection					95:103	N-Glycan Isomer Detection	79:103	N-Glycan Isomer Detection	79:103	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	1	4	theme	effective	364:372	arg1	approach					374:381	an effective approach	361:381	an effective approach for characterization of many disease states	361:425	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	4	theme	effective	364:372	arg1	analysis					184:191	The analysis	180:191	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	180:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	3	5	theme	core	886:889	arg1	glycans					903:909	α1,6-linked core fucosylated glycans	874:909	α1,6-linked core fucosylated glycans	874:909	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	1	6	theme	laser	290:294	arg1	IMS					353:355	IMS	353:355	IMS	353:355	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	6	theme	laser	290:294	arg1	spectrometry					339:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry	274:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	274:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	0	7	theme	Mass	108:111	arg1	Spectrometry					113:124	Mass Spectrometry	108:124	Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues	108:177	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	2	8	theme	localization	620:631	arg1	specificity					599:609	the specificity	595:609	the specificity of their localization within tissue	595:645	As the workflow has matured and new technology emerged, approaches are needed to more efficiently characterize the isomeric structures of these N-glycans to expand on the specificity of their localization within tissue.
33908016	1	9	from	analysis	184:191	arg1	tissues					263:269	formalin-fixed, paraffin-embedded (FFPE) tissues	222:269	formalin-fixed, paraffin-embedded (FFPE) tissues	222:269	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	3	10	theme	fucosylated	891:901	arg1	glycans					903:909	α1,6-linked core fucosylated glycans	874:909	α1,6-linked core fucosylated glycans	874:909	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	1	11	theme	desorption/ionization	296:316	arg1	IMS					353:355	IMS	353:355	IMS	353:355	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	11	theme	desorption/ionization	296:316	arg1	spectrometry					339:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry	274:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	274:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	3	12	gly	fucosylated	891:901	arg1	glycans					903:909	α1,6-linked core fucosylated glycans	874:909	α1,6-linked core fucosylated glycans	874:909	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	2	13	theme	isomeric	543:550	arg1	structures					552:561	the isomeric structures	539:561	the isomeric structures of these N-glycans	539:580	As the workflow has matured and new technology emerged, approaches are needed to more efficiently characterize the isomeric structures of these N-glycans to expand on the specificity of their localization within tissue.
33908016	3	14	theme	sialic	748:753	arg1	acids					755:759	sialic acids	748:759	sialic acids attached to N-glycans	748:781	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	4	15	theme	fucosylation	1174:1185	arg1	isomers					1187:1193	fucosylation isomers	1174:1193	fucosylation isomers	1174:1193	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	1	16	theme	N-glycan	196:203	arg1	distributions					205:217	N-glycan distributions	196:217	N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues	196:269	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	4	17	theme	acid	1054:1057	arg1	linkages					1068:1075	sialic acid isomeric linkages	1047:1075	sialic acid isomeric linkages	1047:1075	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	1	18	theme	many	407:410	arg1	states					420:425	many disease states	407:425	many disease states	407:425	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	3	19	dep	linkage	722:728	arg1	α2,3					731:734	α2,3	731:734	α2,3	731:734	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	19	dep	linkage	722:728	arg1	α2,6					739:742	α2,6	739:742	α2,6	739:742	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	1	20	theme	distributions	205:217	arg1	approach					374:381	an effective approach	361:381	an effective approach for characterization of many disease states	361:425	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	20	theme	distributions	205:217	arg1	analysis					184:191	The analysis	180:191	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	180:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	4	21	theme	sialic	1047:1052	arg1	linkages					1068:1075	sialic acid isomeric linkages	1047:1075	sialic acid isomeric linkages	1047:1075	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	1	22	theme	MALDI	319:323	arg1	IMS					353:355	IMS	353:355	IMS	353:355	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	22	theme	MALDI	319:323	arg1	spectrometry					339:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry	274:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	274:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	0	23	theme	Glycosidase	25:35	arg1	Strategies					64:73	Multiple Glycosidase and Chemical Stabilization Strategies	16:73	Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection	16:103	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	0	24	theme	Formalin-Fixed	137:150	arg1	Tissues					171:177	Formalin-Fixed, Paraffin-Embedded Tissues	137:177	Formalin-Fixed, Paraffin-Embedded Tissues	137:177	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	4	25	theme	F3	1137:1138	arg1	approach					1109:1116	a dual-enzymatic approach	1092:1116	a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section	1092:1220	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	1	26	theme	formalin-fixed	222:235	arg1	tissues					263:269	formalin-fixed, paraffin-embedded (FFPE) tissues	222:269	formalin-fixed, paraffin-embedded (FFPE) tissues	222:269	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	0	27	theme	Multiple	16:23	arg1	Strategies					64:73	Multiple Glycosidase and Chemical Stabilization Strategies	16:73	Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection	16:103	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	1	28	theme	imaging	326:332	arg1	IMS					353:355	IMS	353:355	IMS	353:355	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	28	theme	imaging	326:332	arg1	spectrometry					339:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry	274:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	274:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	29	theme	disease	412:418	arg1	states					420:425	many disease states	407:425	many disease states	407:425	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	4	30	theme	PNGase	1144:1149	arg1	F					1151:1151	endoglycosidase F3 and PNGase F	1121:1151	F	1151:1151	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	4	31	theme	F	1151:1151	arg1	approach					1109:1116	a dual-enzymatic approach	1092:1116	a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section	1092:1220	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	0	32	theme	Chemical	41:48	arg1	Stabilization					50:62	Chemical Stabilization	41:62	Chemical Stabilization	41:62	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	1	33	theme	mass	334:337	arg1	IMS					353:355	IMS	353:355	IMS	353:355	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	33	theme	mass	334:337	arg1	spectrometry					339:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry	274:350	matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	274:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	2	34	theme	N-glycans	572:580	arg1	structures					552:561	the isomeric structures	539:561	the isomeric structures of these N-glycans	539:580	As the workflow has matured and new technology emerged, approaches are needed to more efficiently characterize the isomeric structures of these N-glycans to expand on the specificity of their localization within tissue.
33908016	1	35	theme	states	420:425	arg1	characterization					387:402	characterization	387:402	characterization of many disease states	387:425	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	3	36	theme	fucose	946:951	arg1	linkage					935:941	the linkage	931:941	the linkage of fucose on N-glycans	931:964	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	37	theme	endoglycosidase	790:804	arg1	F3					815:816	F3	815:816	F3	815:816	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	37	theme	endoglycosidase	790:804	arg1	F3					806:807	endoglycosidase F3	790:807	endoglycosidase F3 (Endo F3)	790:817	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	2	38	theme	new	460:462	arg1	technology					464:473	new technology	460:473	new technology	460:473	As the workflow has matured and new technology emerged, approaches are needed to more efficiently characterize the isomeric structures of these N-glycans to expand on the specificity of their localization within tissue.
33908016	0	39	theme	Strategies	64:73	arg1	Optimization					0:11	Optimization	0:11	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.	0:178	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	4	40	theme	isomeric	1059:1066	arg1	linkages					1068:1075	sialic acid isomeric linkages	1047:1075	sialic acid isomeric linkages	1047:1075	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	1	41	from	tissues	263:269	arg1	approach					374:381	an effective approach	361:381	an effective approach for characterization of many disease states	361:425	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	41	from	tissues	263:269	arg1	analysis					184:191	The analysis	180:191	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS)	180:356	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	4	42	theme	tissue	1207:1212	arg1	section					1214:1220	the same tissue section	1198:1220	the same tissue section	1198:1220	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	0	43	theme	Stabilization	50:62	arg1	Strategies					64:73	Multiple Glycosidase and Chemical Stabilization Strategies	16:73	Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection	16:103	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	3	44	from	linkage	935:941	arg1	N-glycans					956:964	N-glycans	956:964	N-glycans	956:964	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	45	attach	attached	761:768	arg2	acids					755:759	sialic acids	748:759	sialic acids attached to N-glycans	748:781	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	45	attach	attached	761:768	arg1	N-glycans					773:781	N-glycans	773:781	N-glycans	773:781	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	46	theme	isomeric	713:720	arg1	linkage					722:728	the isomeric linkage	709:728	the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans	709:781	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	47	theme	acid	655:658	arg1	derivatization					669:682	Sialic acid chemical derivatization	648:682	Sialic acid chemical derivatization	648:682	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	48	theme	acids	755:759	arg1	linkage					722:728	the isomeric linkage	709:728	the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans	709:781	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	49	theme	α1,6-linked	874:884	arg1	glycans					903:909	α1,6-linked core fucosylated glycans	874:909	α1,6-linked core fucosylated glycans	874:909	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	3	50	theme	chemical	660:667	arg1	derivatization					669:682	Sialic acid chemical derivatization	648:682	Sialic acid chemical derivatization	648:682	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	1	51	from	distributions	205:217	arg1	tissues					263:269	formalin-fixed, paraffin-embedded (FFPE) tissues	222:269	formalin-fixed, paraffin-embedded (FFPE) tissues	222:269	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	4	52	theme	endoglycosidase	1121:1135	arg1	F3					1137:1138	endoglycosidase F3 and PNGase F	1121:1151	F3	1137:1138	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	0	53	theme	N-Glycan	79:86	arg1	Detection					95:103	N-Glycan Isomer Detection	79:103	N-Glycan Isomer Detection	79:103	Optimization of Multiple Glycosidase and Chemical Stabilization Strategies for N-Glycan Isomer Detection by Mass Spectrometry Imaging in Formalin-Fixed, Paraffin-Embedded Tissues.
33908016	3	54	link	α1,6-linked	874:884	arg1	glycans					903:909	α1,6-linked core fucosylated glycans	874:909	α1,6-linked core fucosylated glycans	874:909	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	1	55	dep	formalin-fixed	222:235	arg1	FFPE					257:260	FFPE	257:260	FFPE	257:260	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	1	55	dep	formalin-fixed	222:235	arg1	paraffin-embedded					238:254	paraffin-embedded	238:254	paraffin-embedded	238:254	The analysis of N-glycan distributions in formalin-fixed, paraffin-embedded (FFPE) tissues by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is an effective approach for characterization of many disease states.
33908016	4	56	theme	dual-enzymatic	1094:1107	arg1	approach					1109:1116	a dual-enzymatic approach	1092:1116	a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section	1092:1220	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33908016	3	57	theme	Sialic	648:653	arg1	acid					655:658	Sialic acid	648:658	Sialic acid chemical derivatization	648:682	Sialic acid chemical derivatization can be used to determine the isomeric linkage (α2,3 or α2,6) of sialic acids attached to N-glycans, while endoglycosidase F3 (Endo F3) can be enzymatically applied to preferentially release α1,6-linked core fucosylated glycans, further describing the linkage of fucose on N-glycans.
33908016	4	58	theme	same	1202:1205	arg1	section					1214:1220	the same tissue section	1198:1220	the same tissue section	1198:1220	Here we describe workflows where N-glycans are chemically derivatized to reveal sialic acid isomeric linkages, combined with a dual-enzymatic approach of endoglycosidase F3 and PNGase F to further elucidate fucosylation isomers on the same tissue section.
33826885	0	0	theme	native	74:79	arg1	spike					87:91	the native viral spike	70:91	the native viral spike	70:91	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	6	1	from	PNGS	788:791	arg1	proximity					802:810	close proximity	796:810	close proximity	796:810	Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy.
33826885	6	1	from	PNGS	788:791	arg1	pairs					852:856	the N133-N137 and N156-N160 pairs	824:856	pairs	852:856	Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy.
33826885	8	2	theme	immune	1023:1028	arg1	responses					1030:1038	off-target immune responses	1012:1038	off-target immune responses to vaccine antigens	1012:1058	Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.
33826885	2	3	contain	contain	324:330	arg2	candidates					312:321	clinical candidates	303:321	clinical candidates	303:321	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	3	contain	contain	324:330	arg2	trimers					284:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	3	contain	contain	324:330	arg1	candidates					312:321	clinical candidates	303:321	clinical candidates	303:321	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	3	contain	contain	324:330	arg2	holes					337:341	such holes	332:341	such holes	332:341	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	3	contain	contain	324:330	arg1	shield					357:362	shield	357:362	shield	357:362	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	3	contain	contain	324:330	arg1	trimers					284:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	3	4	theme	native	493:498	arg1	Env					506:508	native BG505 Env	493:508	native BG505 Env	493:508	To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT.
33826885	8	5	theme	vaccine	1043:1049	arg1	antigens					1051:1058	vaccine antigens	1043:1058	vaccine antigens	1043:1058	Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.
33826885	6	6	theme	close	796:800	arg1	proximity					802:810	close proximity	796:810	close proximity	796:810	Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy.
33826885	1	7	gly	glycosylation	184:196	arg2	PNGS					204:207	PNGS	204:207	PNGS	204:207	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	7	gly	glycosylation	184:196	arg2	site					198:201	a potential N-linked glycosylation site	163:201	a potential N-linked glycosylation site (PNGS)	163:208	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	7	gly	glycosylation	184:196	arg2	under-occupied					213:226	under-occupied	213:226	under-occupied	213:226	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	2	8	theme	SOSIP	278:282	arg1	candidates					312:321	clinical candidates	303:321	clinical candidates	303:321	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	8	theme	SOSIP	278:282	arg1	trimers					284:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	3	9	theme	NxS	529:531	arg1	sequons					533:539	all 12 NxS sequons	522:539	all 12 NxS sequons on BG505 SOSIP	522:554	To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT.
33826885	6	10	dep	such	813:816	arg1	as					818:819	as	818:819	as	818:819	Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy.
33826885	0	11	theme	viral	81:85	arg1	spike					87:91	the native viral spike	70:91	the native viral spike	70:91	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	2	12	theme	Native-like	266:276	arg1	candidates					312:321	clinical candidates	303:321	clinical candidates	303:321	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	12	theme	Native-like	266:276	arg1	trimers					284:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers	266:290	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	1	13	theme	viral	246:250	arg1	counterparts					252:263	their viral counterparts	240:263	their viral counterparts	240:263	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	2	14	theme	such	332:335	arg1	holes					337:341	such holes	332:341	such holes	332:341	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	1	15	link	N-linked	175:182	arg1	PNGS					204:207	PNGS	204:207	PNGS	204:207	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	15	link	N-linked	175:182	arg1	under-occupied					213:226	under-occupied	213:226	under-occupied	213:226	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	15	link	N-linked	175:182	arg1	site					198:201	a potential N-linked glycosylation site	163:201	a potential N-linked glycosylation site (PNGS)	163:208	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	5	16	theme	site	720:723	arg1	occupancy					698:706	occupancy	698:706	occupancy of the N160 site	698:723	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	2	17	theme	strain-specific	376:390	arg1	antibodies					405:414	strain-specific neutralizing antibodies	376:414	strain-specific neutralizing antibodies (NAbs)	376:421	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	17	theme	strain-specific	376:390	arg1	NAbs					417:420	NAbs	417:420	NAbs	417:420	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	5	18	theme	N160	715:718	arg1	site					720:723	the N160 site	711:723	the N160 site	711:723	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	7	19	gly	occupancy	936:944	arg2	strains					961:967	several Env strains	949:967	several Env strains	949:967	We further apply this approach to improve the occupancy of several Env strains.
33826885	1	20	theme	potential	165:173	arg1	PNGS					204:207	PNGS	204:207	PNGS	204:207	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	20	theme	potential	165:173	arg1	under-occupied					213:226	under-occupied	213:226	under-occupied	213:226	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	20	theme	potential	165:173	arg1	site					198:201	a potential N-linked glycosylation site	163:201	a potential N-linked glycosylation site (PNGS)	163:208	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	0	21	theme	glycan	10:15	arg1	occupancy					17:25	glycan occupancy	10:25	glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike	10:91	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	7	22	theme	several	949:955	arg1	strains					961:967	several Env strains	949:967	several Env strains	949:967	We further apply this approach to improve the occupancy of several Env strains.
33826885	2	23	theme	clinical	303:310	arg1	candidates					312:321	clinical candidates	303:321	clinical candidates	303:321	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	1	24	theme	N-linked	175:182	arg1	PNGS					204:207	PNGS	204:207	PNGS	204:207	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	24	theme	N-linked	175:182	arg1	under-occupied					213:226	under-occupied	213:226	under-occupied	213:226	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	24	theme	N-linked	175:182	arg1	site					198:201	a potential N-linked glycosylation site	163:201	a potential N-linked glycosylation site (PNGS)	163:208	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	7	25	theme	Env	957:959	arg1	strains					961:967	several Env strains	949:967	several Env strains	949:967	We further apply this approach to improve the occupancy of several Env strains.
33826885	4	26	used	occupied	615:622	arg2	PNGS					570:573	All PNGS	566:573	All PNGS	566:573	All PNGS, except N133 and N160, are nearly fully occupied.
33826885	7	27	theme	strains	961:967	arg1	occupancy					936:944	the occupancy	932:944	the occupancy of several Env strains	932:967	We further apply this approach to improve the occupancy of several Env strains.
33826885	1	28	theme	glycosylation	184:196	arg1	PNGS					204:207	PNGS	204:207	PNGS	204:207	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	28	theme	glycosylation	184:196	arg1	under-occupied					213:226	under-occupied	213:226	under-occupied	213:226	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	28	theme	glycosylation	184:196	arg1	site					198:201	a potential N-linked glycosylation site	163:201	a potential N-linked glycosylation site (PNGS)	163:208	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	1	29	from	holes	112:116	arg1	vaccines					143:150	recombinant Env-based vaccines	121:150	recombinant Env-based vaccines	121:150	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	3	30	theme	glycan	449:454	arg1	holes					456:460	glycan holes	449:460	glycan holes	449:460	To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT.
33826885	6	31	theme	N156-N160	842:850	arg1	pairs					852:856	the N133-N137 and N156-N160 pairs	824:856	pairs	852:856	Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy.
33826885	5	32	theme	N133	642:645	arg1	site					647:650	the N133 site	638:650	the N133 site	638:650	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	1	33	theme	Artificial	94:103	arg1	holes					112:116	Artificial glycan holes	94:116	Artificial glycan holes on recombinant Env-based vaccines	94:150	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	3	34	theme	BG505	500:504	arg1	Env					506:508	native BG505 Env	493:508	native BG505 Env	493:508	To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT.
33826885	0	35	theme	HIV-1	38:42	arg1	trimers					53:59	soluble HIV-1 envelope trimers	30:59	soluble HIV-1 envelope trimers	30:59	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	5	36	theme	site	647:650	arg1	Occupancy					625:633	Occupancy	625:633	Occupancy of the N133 site	625:650	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	5	37	theme	nearby	754:759	arg1	sequon					766:771	the nearby N156 sequon	750:771	the nearby N156 sequon to NxS	750:778	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	0	38	theme	soluble	30:36	arg1	trimers					53:59	soluble HIV-1 envelope trimers	30:59	soluble HIV-1 envelope trimers	30:59	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	6	39	theme	N133-N137	828:836	arg1	pairs					852:856	the N133-N137 and N156-N160 pairs	824:856	pairs	852:856	Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy.
33826885	2	40	theme	neutralizing	392:403	arg1	antibodies					405:414	strain-specific neutralizing antibodies	376:414	strain-specific neutralizing antibodies (NAbs)	376:421	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	2	40	theme	neutralizing	392:403	arg1	NAbs					417:420	NAbs	417:420	NAbs	417:420	Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs.
33826885	0	41	theme	trimers	53:59	arg1	occupancy					17:25	glycan occupancy	10:25	glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike	10:91	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	8	42	theme	glycan	981:986	arg1	occupancy					988:996	Increasing glycan occupancy	970:996	Increasing glycan occupancy	970:996	Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.
33826885	0	43	gly	occupancy	17:25	arg2	trimers					53:59	soluble HIV-1 envelope trimers	30:59	soluble HIV-1 envelope trimers	30:59	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	1	44	theme	glycan	105:110	arg1	holes					112:116	Artificial glycan holes	94:116	Artificial glycan holes on recombinant Env-based vaccines	94:150	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	0	45	theme	envelope	44:51	arg1	trimers					53:59	soluble HIV-1 envelope trimers	30:59	soluble HIV-1 envelope trimers	30:59	Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.
33826885	8	46	theme	Increasing	970:979	arg1	occupancy					988:996	Increasing glycan occupancy	970:996	Increasing glycan occupancy	970:996	Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.
33826885	5	47	dep	increased	655:663	arg1	whereas					690:696	whereas	690:696	whereas	690:696	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	5	48	gly	occupancy	698:706	arg2	site					720:723	the N160 site	711:723	the N160 site	711:723	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	1	49	theme	recombinant	121:131	arg1	vaccines					143:150	recombinant Env-based vaccines	121:150	recombinant Env-based vaccines	121:150	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	3	50	from	sequons	533:539	arg1	SOSIP					550:554	BG505 SOSIP	544:554	BG505 SOSIP	544:554	To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT.
33826885	8	51	theme	off-target	1012:1021	arg1	responses					1030:1038	off-target immune responses	1012:1038	off-target immune responses to vaccine antigens	1012:1058	Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.
33826885	5	52	theme	N156	761:764	arg1	sequon					766:771	the nearby N156 sequon	750:771	the nearby N156 sequon to NxS	750:778	Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS.
33826885	1	53	theme	Env-based	133:141	arg1	vaccines					143:150	recombinant Env-based vaccines	121:150	recombinant Env-based vaccines	121:150	Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts.
33826885	3	54	gly	glycosylation	476:488	arg1	Env					506:508	native BG505 Env	493:508	native BG505 Env	493:508	To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT.
33826885	3	55	theme	Env	506:508	arg1	glycosylation					476:488	the glycosylation	472:488	the glycosylation of native BG505 Env	472:508	To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT.
33676668	4	0	theme	greater	907:913	arg1	ability					915:921	a greater ability	905:921	not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides	844:953	The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides.
33676668	3	1	theme	new	540:542	arg1	effective					639:647	effective	639:647	effective	639:647	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	3	1	theme	new	540:542	arg1	type					544:547	a new type	538:547	a new type	538:547	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	3	2	dep	carriers	711:718	arg1	expressed					721:729	expressed	721:729	expressed as GO-DA-JR	721:741	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	3	3	theme	specific	756:763	arg1	enrichment					765:774	highly specific enrichment	749:774	highly specific enrichment of N-glycopeptides	749:793	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	6	4	theme	better	1331:1336	arg1	capacity					1349:1356	better enrichment capacity	1331:1356	better enrichment capacity (up to 150 mg/g)	1331:1373	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	3	5	from	type	544:547	arg1	interactions					597:608	electrostatic interactions	583:608	electrostatic interactions	583:608	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	7	6	theme	egood	1479:1483	arg1	selectivity					1496:1506	egood enrichment selectivity	1479:1506	egood enrichment selectivity from real biological samples	1479:1535	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	5	7	gly	glycopeptides	1173:1185	arg2	glycopeptides					1173:1185	glycopeptides	1173:1185	glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests	1173:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	7	gly	glycopeptides	1173:1185	arg1	samples					1200:1206	complex samples	1192:1206	complex samples containing 100-fold bovine serum albumin tryptic digests	1192:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	8	8	from	applications	1654:1665	arg1	proteomics					1730:1739	post-translational modification proteomics	1698:1739	post-translational modification proteomics	1698:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	3	9	theme	composite	564:572	arg1	based					574:578	hydrophilic composite based	552:578	hydrophilic composite based on electrostatic interactions	552:608	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	7	10	theme	biological	1518:1527	arg1	samples					1529:1535	real biological samples	1513:1535	real biological samples	1513:1535	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	1	11	theme	important	222:230	arg1	role					232:235	an important role	219:235	an important role	219:235	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	7	12	from	samples	1529:1535	arg1	selectivity					1496:1506	egood enrichment selectivity	1479:1506	egood enrichment selectivity from real biological samples	1479:1535	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	5	13	gly	glycopeptides	967:979	arg2	glycopeptides					967:979	Thirty-two glycopeptides	956:979	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests	956:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	13	gly	glycopeptides	967:979	arg1	digests					1029:1035	human serum immunoglobulin G (IgG) tryptic digests	986:1035	human serum immunoglobulin G (IgG) tryptic digests	986:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	7	14	theme	human	1457:1461	arg1	serum					1463:1467	human serum	1457:1467	human serum	1457:1467	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	2	15	theme	glycopeptide	313:324	arg1	forms					326:330	glycopeptide forms	313:330	glycopeptide forms	313:330	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	7	16	theme	analysis	1443:1450	arg1	results					1390:1396	the results	1386:1396	the results of glycopeptide enrichment and glycosylation analysis from human serum	1386:1467	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	5	17	theme	high	1122:1125	arg1	performance					1127:1137	high performance	1122:1137	high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests	1122:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	4	18	theme	glycosylated	933:944	arg1	peptides					946:953	glycosylated peptides	933:953	glycosylated peptides	933:953	The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides.
33676668	6	19	theme	higher	1292:1297	arg1	sensitivity					1299:1309	higher sensitivity	1292:1309	higher sensitivity (1 fmol/μL IgG)	1292:1325	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	6	19	theme	higher	1292:1297	arg1	IgG					1322:1324	1 fmol/μL IgG	1312:1324	1 fmol/μL IgG	1312:1324	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	7	20	theme	glycopeptide	1401:1412	arg1	enrichment					1414:1423	glycopeptide enrichment	1401:1423	glycopeptide enrichment	1401:1423	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	3	21	from	interactions	597:608	arg1	effective					639:647	effective	639:647	effective	639:647	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	3	21	from	interactions	597:608	arg1	type					544:547	a new type	538:547	a new type	538:547	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	5	22	theme	human	986:990	arg1	G					1013:1013	human serum immunoglobulin G	986:1013	human serum immunoglobulin G (IgG) tryptic digests	986:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	22	theme	human	986:990	arg1	IgG					1016:1018	IgG	1016:1018	IgG	1016:1018	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	7	23	from	serum	1463:1467	arg1	results					1390:1396	the results	1386:1396	the results of glycopeptide enrichment and glycosylation analysis from human serum	1386:1467	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	5	24	theme	glycopeptides	1173:1185	arg1	enrichment					1159:1168	anti-interfering enrichment	1142:1168	anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests	1142:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	4	25	gly	glycosylated	933:944	arg1	peptides					946:953	glycosylated peptides	933:953	glycosylated peptides	933:953	The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides.
33676668	5	26	theme	complex	1192:1198	arg1	samples					1200:1206	complex samples	1192:1206	complex samples containing 100-fold bovine serum albumin tryptic digests	1192:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	2	27	from	samples	475:481	arg1	glycopeptides					415:427	capture and separate glycopeptides	394:427	capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis	394:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	5	28	from	performance	1127:1137	arg1	enrichment					1159:1168	anti-interfering enrichment	1142:1168	anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests	1142:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	1	29	theme	post-translational	163:180	arg1	modifications					182:194	the most important post-translational modifications	144:194	the most important post-translational modifications of proteins	144:206	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	4	30	theme	cellulose	825:833	arg1	introduction					800:811	The introduction	796:811	The introduction of cationic cellulose	796:833	The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides.
33676668	0	31	from	composites	55:64	arg1	enrichment					108:117	N-Glycopeptides enrichment	92:117	N-Glycopeptides enrichment	92:117	Hydrophilic graphene oxide-dopamine-cationic cellulose composites and their applications in N-Glycopeptides enrichment.
33676668	0	32	theme	Hydrophilic	0:10	arg1	composites					55:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites and their applications in N-Glycopeptides enrichment.
33676668	5	33	theme	immunoglobulin	998:1011	arg1	G					1013:1013	human serum immunoglobulin G	986:1013	human serum immunoglobulin G (IgG) tryptic digests	986:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	33	theme	immunoglobulin	998:1011	arg1	IgG					1016:1018	IgG	1016:1018	IgG	1016:1018	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	2	34	theme	biological	464:473	arg1	samples					475:481	complex biological samples	456:481	complex biological samples with mass spectrometric analysis	456:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	0	35	theme	oxide-dopamine-cationic	21:43	arg1	composites					55:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites and their applications in N-Glycopeptides enrichment.
33676668	3	36	theme	graphene	687:694	arg1	carriers					711:718	graphene oxide-dopamine carriers	687:718	graphene oxide-dopamine carriers (expressed as GO-DA-JR)	687:742	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	4	37	theme	surface	863:869	arg1	charge					871:876	a perfect surface charge	853:876	not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides	844:953	The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides.
33676668	2	38	theme	high	434:437	arg1	selectivity					439:449	high selectivity	434:449	high selectivity	434:449	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	5	39	from	samples	1200:1206	arg1	enrichment					1159:1168	anti-interfering enrichment	1142:1168	anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests	1142:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	39	from	samples	1200:1206	arg1	glycopeptides					1173:1185	glycopeptides	1173:1185	glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests	1173:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	40	theme	improved	1066:1073	arg1	S/N					1098:1100	S/N	1098:1100	S/N	1098:1100	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	40	theme	improved	1066:1073	arg1	ratio					1091:1095	a greatly improved signal-to-noise ratio	1056:1095	a greatly improved signal-to-noise ratio (S/N)	1056:1101	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	2	41	theme	spectrometric	493:505	arg1	analysis					507:514	mass spectrometric analysis	488:514	mass spectrometric analysis	488:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	5	42	theme	bovine	1228:1233	arg1	albumin					1241:1247	100-fold bovine serum albumin tryptic digests	1219:1263	100-fold bovine serum albumin tryptic digests	1219:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	2	43	theme	abundance	346:354	arg1	diversity					300:308	the diversity	296:308	the diversity of glycopeptide forms and their low abundance	296:354	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	8	44	theme	glycopeptides	1670:1682	arg1	enrichment					1684:1693	glycopeptides enrichment	1670:1693	glycopeptides enrichment in post-translational modification proteomics	1670:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	2	45	gly	glycopeptide	313:324	arg2	glycopeptide					313:324	glycopeptide	313:324	glycopeptide	313:324	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	5	46	from	digests	1029:1035	arg1	glycopeptides					967:979	Thirty-two glycopeptides	956:979	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests	956:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	2	47	with	glycopeptides	415:427	arg1	selectivity					439:449	high selectivity	434:449	high selectivity	434:449	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	8	48	theme	modification	1717:1728	arg1	proteomics					1730:1739	post-translational modification proteomics	1698:1739	post-translational modification proteomics	1698:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	6	49	theme	enrichment	1338:1347	arg1	capacity					1349:1356	better enrichment capacity	1331:1356	better enrichment capacity (up to 150 mg/g)	1331:1373	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	3	50	theme	based	574:578	arg1	effective					639:647	effective	639:647	effective	639:647	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	3	50	theme	based	574:578	arg1	type					544:547	a new type	538:547	a new type	538:547	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	3	51	theme	hydrophilic	552:562	arg1	based					574:578	hydrophilic composite based	552:578	hydrophilic composite based on electrostatic interactions	552:608	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	7	52	theme	real	1513:1516	arg1	samples					1529:1535	real biological samples	1513:1535	real biological samples	1513:1535	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	7	53	theme	enrichment	1485:1494	arg1	selectivity					1496:1506	egood enrichment selectivity	1479:1506	egood enrichment selectivity from real biological samples	1479:1535	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	7	54	gly	glycopeptide	1401:1412	arg2	glycopeptide					1401:1412	glycopeptide enrichment	1401:1423	glycopeptide enrichment	1401:1423	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	2	55	theme	forms	326:330	arg1	diversity					300:308	the diversity	296:308	the diversity of glycopeptide forms and their low abundance	296:354	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	3	56	theme	N-glycopeptides	779:793	arg1	enrichment					765:774	highly specific enrichment	749:774	highly specific enrichment of N-glycopeptides	749:793	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	8	57	from	enrichment	1684:1693	arg1	proteomics					1730:1739	post-translational modification proteomics	1698:1739	post-translational modification proteomics	1698:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	8	58	theme	high	1575:1578	arg1	selectivity					1562:1572	high selectivity	1557:1572	high selectivity	1557:1572	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	8	58	theme	high	1575:1578	arg1	sensitivity					1580:1590	high sensitivity	1575:1590	high sensitivity	1575:1590	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	7	59	theme	glycosylation	1429:1441	arg1	analysis					1443:1450	glycosylation analysis	1429:1450	glycosylation analysis	1429:1450	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	8	60	from	proteomics	1730:1739	arg1	applications					1654:1665	applications	1654:1665	applications of glycopeptides enrichment in post-translational modification proteomics	1654:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	2	61	with	samples	475:481	arg1	analysis					507:514	mass spectrometric analysis	488:514	mass spectrometric analysis	488:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	1	62	theme	important	153:161	arg1	modifications					182:194	the most important post-translational modifications	144:194	the most important post-translational modifications of proteins	144:206	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	3	63	theme	electrostatic	583:595	arg1	interactions					597:608	electrostatic interactions	583:608	electrostatic interactions	583:608	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	5	64	contain	containing	1208:1217	arg2	albumin					1241:1247	100-fold bovine serum albumin tryptic digests	1219:1263	100-fold bovine serum albumin tryptic digests	1219:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	64	contain	containing	1208:1217	arg1	samples					1200:1206	complex samples	1192:1206	complex samples containing 100-fold bovine serum albumin tryptic digests	1192:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	8	65	theme	high	1557:1560	arg1	selectivity					1562:1572	high selectivity	1557:1572	high selectivity	1557:1572	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	8	65	theme	high	1557:1560	arg1	sensitivity					1580:1590	high sensitivity	1575:1590	high sensitivity	1575:1590	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	8	65	theme	high	1557:1560	arg1	stability					1598:1606	good stability	1593:1606	good stability	1593:1606	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	8	65	theme	high	1557:1560	arg1	operability					1612:1622	operability	1612:1622	operability	1612:1622	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	7	66	theme	enrichment	1414:1423	arg1	results					1390:1396	the results	1386:1396	the results of glycopeptide enrichment and glycosylation analysis from human serum	1386:1467	Moreover, the results of glycopeptide enrichment and glycosylation analysis from human serum also show egood enrichment selectivity from real biological samples.
33676668	0	67	theme	N-Glycopeptides	92:106	arg1	enrichment					108:117	N-Glycopeptides enrichment	92:117	N-Glycopeptides enrichment	92:117	Hydrophilic graphene oxide-dopamine-cationic cellulose composites and their applications in N-Glycopeptides enrichment.
33676668	1	68	theme	modifications	182:194	arg1	one					137:139	one	137:139	one	137:139	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	1	68	theme	modifications	182:194	arg1	modifications					182:194	the most important post-translational modifications	144:194	the most important post-translational modifications of proteins	144:206	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	1	69	theme	proteins	199:206	arg1	modifications					182:194	the most important post-translational modifications	144:194	the most important post-translational modifications of proteins	144:206	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	8	70	theme	good	1593:1596	arg1	selectivity					1562:1572	high selectivity	1557:1572	high selectivity	1557:1572	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	8	70	theme	good	1593:1596	arg1	stability					1598:1606	good stability	1593:1606	good stability	1593:1606	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	5	71	dep	albumin	1241:1247	arg1	digests					1257:1263	tryptic digests	1249:1263	100-fold bovine serum albumin tryptic digests	1219:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	3	72	from	based	574:578	arg1	interactions					597:608	electrostatic interactions	583:608	electrostatic interactions	583:608	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	0	73	from	applications	76:87	arg1	enrichment					108:117	N-Glycopeptides enrichment	92:117	N-Glycopeptides enrichment	92:117	Hydrophilic graphene oxide-dopamine-cationic cellulose composites and their applications in N-Glycopeptides enrichment.
33676668	5	74	theme	anti-interfering	1142:1157	arg1	enrichment					1159:1168	anti-interfering enrichment	1142:1168	anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests	1142:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	75	theme	tryptic	1021:1027	arg1	digests					1029:1035	human serum immunoglobulin G (IgG) tryptic digests	986:1035	human serum immunoglobulin G (IgG) tryptic digests	986:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	3	76	gly	N-glycopeptides	779:793	arg2	N-glycopeptides					779:793	N-glycopeptides	779:793	N-glycopeptides	779:793	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	2	77	gly	glycopeptides	415:427	arg1	samples					475:481	complex biological samples	456:481	complex biological samples with mass spectrometric analysis	456:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	2	77	gly	glycopeptides	415:427	arg2	glycopeptides					415:427	capture and separate glycopeptides	394:427	capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis	394:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	4	78	theme	cationic	816:823	arg1	cellulose					825:833	cationic cellulose	816:833	cationic cellulose	816:833	The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides.
33676668	2	79	theme	separate	406:413	arg1	glycopeptides					415:427	capture and separate glycopeptides	394:427	capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis	394:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	0	80	theme	graphene	12:19	arg1	composites					55:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites and their applications in N-Glycopeptides enrichment.
33676668	5	81	theme	serum	992:996	arg1	G					1013:1013	human serum immunoglobulin G	986:1013	human serum immunoglobulin G (IgG) tryptic digests	986:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	81	theme	serum	992:996	arg1	IgG					1016:1018	IgG	1016:1018	IgG	1016:1018	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	6	82	contain	has	1288:1290	arg2	sensitivity					1299:1309	higher sensitivity	1292:1309	higher sensitivity (1 fmol/μL IgG)	1292:1325	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	6	82	contain	has	1288:1290	arg1	GO-DA-JR					1279:1286	GO-DA-JR	1279:1286	GO-DA-JR	1279:1286	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	6	82	contain	has	1288:1290	arg2	IgG					1322:1324	1 fmol/μL IgG	1312:1324	1 fmol/μL IgG	1312:1324	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	6	82	contain	has	1288:1290	arg2	capacity					1349:1356	better enrichment capacity	1331:1356	better enrichment capacity (up to 150 mg/g)	1331:1373	In addition, GO-DA-JR has higher sensitivity (1 fmol/μL IgG) and better enrichment capacity (up to 150 mg/g).
33676668	2	83	theme	capture	394:400	arg1	glycopeptides					415:427	capture and separate glycopeptides	394:427	capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis	394:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	0	84	theme	cellulose	45:53	arg1	composites					55:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites	0:64	Hydrophilic graphene oxide-dopamine-cationic cellulose composites and their applications in N-Glycopeptides enrichment.
33676668	5	85	theme	tryptic	1249:1255	arg1	digests					1257:1263	tryptic digests	1249:1263	100-fold bovine serum albumin tryptic digests	1219:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	86	theme	G	1013:1013	arg1	digests					1029:1035	human serum immunoglobulin G (IgG) tryptic digests	986:1035	human serum immunoglobulin G (IgG) tryptic digests	986:1035	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	2	87	theme	complex	456:462	arg1	samples					475:481	complex biological samples	456:481	complex biological samples with mass spectrometric analysis	456:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	8	88	gly	glycopeptides	1670:1682	arg2	glycopeptides					1670:1682	glycopeptides enrichment	1670:1693	glycopeptides enrichment in post-translational modification proteomics	1670:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	3	89	theme	cationic	665:672	arg1	cellulose					674:682	cationic cellulose	665:682	cationic cellulose	665:682	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	4	90	theme	perfect	855:861	arg1	charge					871:876	a perfect surface charge	853:876	not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides	844:953	The introduction of cationic cellulose provides not only a perfect surface charge for the composite but also a greater ability to enrich glycosylated peptides.
33676668	5	91	theme	signal-to-noise	1075:1089	arg1	S/N					1098:1100	S/N	1098:1100	S/N	1098:1100	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	5	91	theme	signal-to-noise	1075:1089	arg1	ratio					1091:1095	a greatly improved signal-to-noise ratio	1056:1095	a greatly improved signal-to-noise ratio (S/N)	1056:1101	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	2	92	theme	mass	488:491	arg1	analysis					507:514	mass spectrometric analysis	488:514	mass spectrometric analysis	488:514	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	5	93	theme	serum	1235:1239	arg1	albumin					1241:1247	100-fold bovine serum albumin tryptic digests	1219:1263	100-fold bovine serum albumin tryptic digests	1219:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	8	94	theme	enrichment	1684:1693	arg1	applications					1654:1665	applications	1654:1665	applications of glycopeptides enrichment in post-translational modification proteomics	1654:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	3	95	theme	oxide-dopamine	696:709	arg1	carriers					711:718	graphene oxide-dopamine carriers	687:718	graphene oxide-dopamine carriers (expressed as GO-DA-JR)	687:742	Here, we synthesized a new type of hydrophilic composite based on electrostatic interactions, which has been proven to be effective in immobilizing cationic cellulose on graphene oxide-dopamine carriers (expressed as GO-DA-JR), for highly specific enrichment of N-glycopeptides.
33676668	1	96	dep	structure	244:252	arg1	the					240:242	the	240:242	the	240:242	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	2	97	theme	low	342:344	arg1	abundance					346:354	their low abundance	336:354	their low abundance	336:354	However, due to the diversity of glycopeptide forms and their low abundance, it is extraordinarily challenging to capture and separate glycopeptides with high selectivity from complex biological samples with mass spectrometric analysis.
33676668	8	98	theme	post-translational	1698:1715	arg1	modification					1717:1728	post-translational modification	1698:1728	post-translational modification proteomics	1698:1739	This work exhibits high selectivity, high sensitivity, good stability and operability, indicating its potential for applications of glycopeptides enrichment in post-translational modification proteomics.
33676668	5	99	from	enrichment	1159:1168	arg1	samples					1200:1206	complex samples	1192:1206	complex samples containing 100-fold bovine serum albumin tryptic digests	1192:1263	Thirty-two glycopeptides from human serum immunoglobulin G (IgG) tryptic digests were observed with a greatly improved signal-to-noise ratio (S/N) and also presented high performance in anti-interfering enrichment of glycopeptides from complex samples containing 100-fold bovine serum albumin tryptic digests.
33676668	1	100	theme	proteins	270:277	arg1	function					258:265	function	258:265	function	258:265	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
33676668	1	100	theme	proteins	270:277	arg1	structure					244:252	structure	244:252	structure	244:252	Glycosylation is one of the most important post-translational modifications of proteins, and plays an important role in the structure and function of proteins.
32134190	0	0	theme	strategies	88:97	arg1	evaluation					53:62	swift evaluation	47:62	swift evaluation of N-glycan engineering strategies	47:97	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	8	1	theme	key	1202:1204	arg1	glycosyltransferases					1221:1240	key Golgi-resident glycosyltransferases	1202:1240	key Golgi-resident glycosyltransferases	1202:1240	The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions.
32134190	7	2	theme	approaches	1067:1076	arg1	assessment					1041:1050	a quick assessment	1033:1050	a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity	1033:1138	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	3	3	theme	high	505:508	arg1	degrees					510:516	high degrees	505:516	high degrees of branching	505:529	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	5	4	theme	capable	769:775	arg1	system					762:767	an mRNA transfection system	741:767	an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load	741:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	4	5	theme	many	592:595	arg1	factors					615:621	many other influential factors	592:621	many other influential factors	592:621	Among many other influential factors, the level of productivity can steer N-glycosylation towards less mature N-glycan structures.
32134190	0	6	theme	engineering	76:86	arg1	strategies					88:97	N-glycan engineering strategies	67:97	N-glycan engineering strategies	67:97	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	6	7	theme	engineering	934:944	arg1	strategies					946:955	engineering strategies	934:955	engineering strategies for enhanced N-glycan processing	934:988	Here, this system was applied to evaluate engineering strategies for enhanced N-glycan processing.
32134190	5	8	theme	mRNA	744:747	arg1	system					762:767	an mRNA transfection system	741:767	an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load	741:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	4	9	theme	influential	603:613	arg1	factors					615:621	many other influential factors	592:621	many other influential factors	592:621	Among many other influential factors, the level of productivity can steer N-glycosylation towards less mature N-glycan structures.
32134190	5	10	theme	transfection	749:760	arg1	system					762:767	an mRNA transfection system	741:767	an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load	741:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	4	11	theme	other	597:601	arg1	factors					615:621	many other influential factors	592:621	many other influential factors	592:621	Among many other influential factors, the level of productivity can steer N-glycosylation towards less mature N-glycan structures.
32134190	9	12	from	Changes	1291:1297	arg1	sialylation					1319:1329	sialylation	1319:1329	sialylation	1319:1329	Changes in galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation were evaluated.
32134190	9	12	from	Changes	1291:1297	arg1	galactosylation					1302:1316	galactosylation	1302:1316	galactosylation	1302:1316	Changes in galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation were evaluated.
32134190	9	12	from	Changes	1291:1297	arg1	formation					1387:1395	N-acetyllactosamine formation	1367:1395	galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation	1302:1395	Changes in galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation were evaluated.
32134190	9	12	from	Changes	1291:1297	arg1	potential					1346:1354	branching potential	1336:1354	branching potential	1336:1354	Changes in galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation were evaluated.
32134190	3	13	theme	homogenous	427:436	arg1	structures					438:447	homogenous structures	427:447	homogenous structures with a more demanding level of processing	427:489	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	3	14	theme	Stable	406:411	arg1	production					413:422	Stable production	406:422	Stable production	406:422	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	2	15	theme	N-glycan	281:288	arg1	profiles					290:297	desired N-glycan profiles	273:297	desired N-glycan profiles that may vary for different proteins in a reproducible manner	273:359	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	1	16	theme	complex	174:180	arg1	therapeutics					193:204	complex biological therapeutics	174:204	complex biological therapeutics	174:204	N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics.
32134190	5	17	theme	stepwise	832:839	arg1	increase					841:848	stepwise increase	832:848	stepwise increase of intracellular model protein mRNA load	832:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	7	18	theme	high	1122:1125	arg1	productivity					1127:1138	high productivity	1122:1138	high productivity	1122:1138	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	3	19	dep	instance	496:503	arg1	degrees					510:516	high degrees	505:516	high degrees of branching	505:529	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	8	20	theme	gene	1145:1148	arg1	approaches					1158:1167	The gene editing approaches	1141:1167	The gene editing approaches tested	1141:1174	The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions.
32134190	1	21	theme	biological	182:191	arg1	therapeutics					193:204	complex biological therapeutics	174:204	complex biological therapeutics	174:204	N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics.
32134190	9	22	theme	N-acetyllactosamine	1367:1385	arg1	formation					1387:1395	N-acetyllactosamine formation	1367:1395	galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation	1302:1395	Changes in galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation were evaluated.
32134190	2	23	theme	different	317:325	arg1	proteins					327:334	different proteins	317:334	different proteins	317:334	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	1	24	theme	therapeutics	193:204	arg1	majority					162:169	the majority	158:169	the majority of complex biological therapeutics	158:204	N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics.
32134190	0	25	theme	encoding	29:36	arg1	mRNA					38:41	glycoprotein encoding mRNA	16:41	glycoprotein encoding mRNA	16:41	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	7	26	from	productivity	1127:1138	arg1	capacity					1110:1117	the cellular N-glycosylation capacity	1081:1117	the cellular N-glycosylation capacity at high productivity	1081:1138	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	2	27	dep	demand	254:259	arg1	generate					264:271	generate	264:271	to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner	261:359	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	4	28	theme	productivity	637:648	arg1	level					628:632	the level	624:632	the level of productivity	624:648	Among many other influential factors, the level of productivity can steer N-glycosylation towards less mature N-glycan structures.
32134190	0	29	theme	glycoprotein	16:27	arg1	mRNA					38:41	glycoprotein encoding mRNA	16:41	glycoprotein encoding mRNA	16:41	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	7	30	theme	quick	1035:1039	arg1	assessment					1041:1050	a quick assessment	1033:1050	a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity	1033:1138	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	5	31	theme	protein	873:879	arg1	load					886:889	intracellular model protein mRNA load	853:889	intracellular model protein mRNA load	853:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	4	32	theme	mature	689:694	arg1	structures					705:714	less mature N-glycan structures	684:714	less mature N-glycan structures	684:714	Among many other influential factors, the level of productivity can steer N-glycosylation towards less mature N-glycan structures.
32134190	7	33	theme	cellular	1085:1092	arg1	capacity					1110:1117	the cellular N-glycosylation capacity	1081:1117	the cellular N-glycosylation capacity at high productivity	1081:1138	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	7	34	from	assessment	1041:1050	arg1	capacity					1110:1117	the cellular N-glycosylation capacity	1081:1117	the cellular N-glycosylation capacity at high productivity	1081:1138	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	3	35	theme	structures	438:447	arg1	production					413:422	Stable production	406:422	Stable production	406:422	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	5	36	theme	mRNA	881:884	arg1	load					886:889	intracellular model protein mRNA load	853:889	intracellular model protein mRNA load	853:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	0	37	theme	mRNA	38:41	arg1	Transfection					0:11	Transfection	0:11	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.	0:98	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	5	38	theme	secretory	811:819	arg1	pathway					821:827	the secretory pathway	807:827	the secretory pathway	807:827	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	8	39	theme	gene	1275:1278	arg1	deletions					1280:1288	multiple gene deletions	1266:1288	multiple gene deletions	1266:1288	The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions.
32134190	3	40	theme	demanding	461:469	arg1	level					471:475	a more demanding level	454:475	a more demanding level of processing	454:489	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	8	41	theme	glycosyltransferases	1221:1240	arg1	overexpression					1184:1197	overexpression	1184:1197	overexpression	1184:1197	The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions.
32134190	8	42	theme	editing	1150:1156	arg1	approaches					1158:1167	The gene editing approaches	1141:1167	The gene editing approaches tested	1141:1174	The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions.
32134190	0	43	gly	glycoprotein	16:27	arg1	glycoprotein					16:27	glycoprotein encoding mRNA	16:41	glycoprotein encoding mRNA	16:41	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	7	44	theme	N-glycosylation	1094:1108	arg1	capacity					1110:1117	the cellular N-glycosylation capacity	1081:1117	the cellular N-glycosylation capacity at high productivity	1081:1138	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	0	45	theme	swift	47:51	arg1	evaluation					53:62	swift evaluation	47:62	swift evaluation of N-glycan engineering strategies	47:97	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	6	46	theme	N-glycan	970:977	arg1	processing					979:988	enhanced N-glycan processing	961:988	enhanced N-glycan processing	961:988	Here, this system was applied to evaluate engineering strategies for enhanced N-glycan processing.
32134190	3	47	with	structures	438:447	arg1	level					471:475	a more demanding level	454:475	a more demanding level of processing	454:489	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	2	48	theme	N-glycan	220:227	arg1	efforts					241:247	many N-glycan engineering efforts	215:247	many N-glycan engineering efforts	215:247	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	2	49	theme	engineering	229:239	arg1	efforts					241:247	many N-glycan engineering efforts	215:247	many N-glycan engineering efforts	215:247	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	2	50	theme	reproducible	341:352	arg1	manner					354:359	a reproducible manner	339:359	a reproducible manner	339:359	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	6	51	theme	enhanced	961:968	arg1	processing					979:988	enhanced N-glycan processing	961:988	enhanced N-glycan processing	961:988	Here, this system was applied to evaluate engineering strategies for enhanced N-glycan processing.
32134190	7	52	theme	engineering	1055:1065	arg1	approaches					1067:1076	engineering approaches	1055:1076	engineering approaches	1055:1076	The tool proves to indeed be valuable for a quick assessment of engineering approaches on the cellular N-glycosylation capacity at high productivity.
32134190	2	53	theme	many	215:218	arg1	efforts					241:247	many N-glycan engineering efforts	215:247	many N-glycan engineering efforts	215:247	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	2	54	theme	desired	273:279	arg1	profiles					290:297	desired N-glycan profiles	273:297	desired N-glycan profiles that may vary for different proteins in a reproducible manner	273:359	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	4	55	theme	N-glycan	696:703	arg1	structures					705:714	less mature N-glycan structures	684:714	less mature N-glycan structures	684:714	Among many other influential factors, the level of productivity can steer N-glycosylation towards less mature N-glycan structures.
32134190	1	56	theme	key	132:134	arg1	N-glycosylation					100:114	N-glycosylation	100:114	N-glycosylation	100:114	N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics.
32134190	1	56	theme	key	132:134	arg1	attribute					144:152	a key quality attribute	130:152	a key quality attribute for the majority of complex biological therapeutics	130:204	N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics.
32134190	8	57	theme	multiple	1266:1273	arg1	deletions					1280:1288	multiple gene deletions	1266:1288	multiple gene deletions	1266:1288	The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions.
32134190	3	58	theme	terminal	535:542	arg1	sialylation					544:554	terminal sialylation	535:554	terminal sialylation	535:554	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	1	59	theme	quality	136:142	arg1	N-glycosylation					100:114	N-glycosylation	100:114	N-glycosylation	100:114	N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics.
32134190	1	59	theme	quality	136:142	arg1	attribute					144:152	a key quality attribute	130:152	a key quality attribute for the majority of complex biological therapeutics	130:204	N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics.
32134190	3	60	theme	processing	480:489	arg1	level					471:475	a more demanding level	454:475	a more demanding level of processing	454:489	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	0	61	theme	N-glycan	67:74	arg1	strategies					88:97	N-glycan engineering strategies	67:97	N-glycan engineering strategies	67:97	Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.
32134190	5	62	theme	load	886:889	arg1	increase					841:848	stepwise increase	832:848	stepwise increase of intracellular model protein mRNA load	832:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	5	63	theme	model	867:871	arg1	load					886:889	intracellular model protein mRNA load	853:889	intracellular model protein mRNA load	853:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	9	64	theme	branching	1336:1344	arg1	potential					1346:1354	branching potential	1336:1354	branching potential	1336:1354	Changes in galactosylation, sialylation, and branching potential as well as N-acetyllactosamine formation were evaluated.
32134190	2	65	theme	many	394:397	arg1	cases					399:403	many cases	394:403	many cases	394:403	Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases.
32134190	5	66	theme	intracellular	853:865	arg1	load					886:889	intracellular model protein mRNA load	853:889	intracellular model protein mRNA load	853:889	Recently, we introduced an mRNA transfection system capable of elucidating bottlenecks in the secretory pathway by stepwise increase of intracellular model protein mRNA load.
32134190	3	67	theme	branching	521:529	arg1	degrees					510:516	high degrees	505:516	high degrees of branching	505:529	Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.
32134190	8	68	theme	Golgi-resident	1206:1219	arg1	glycosyltransferases					1221:1240	key Golgi-resident glycosyltransferases	1202:1240	key Golgi-resident glycosyltransferases	1202:1240	The gene editing approaches tested include overexpression of key Golgi-resident glycosyltransferases, partially coupled with multiple gene deletions.
32031706	0	0	theme	Chlorella	69:77	arg1	microalgae					79:88	Chlorella microalgae	69:88	Chlorella microalgae	69:88	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.
32031706	0	1	from	view	8:11	arg1	diversity					43:51	the unsuspected intragenus diversity	16:51	the unsuspected intragenus diversity of N-glycans in Chlorella microalgae	16:88	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.
32031706	5	2	theme	different	702:710	arg1	types					721:725	different and rare types	702:725	different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine)	702:793	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	8	3	from	light	1230:1234	arg1	astonishing					1370:1380	astonishing	1370:1380	astonishing	1370:1380	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	8	3	from	light	1230:1234	arg1	diversity					1357:1365	the herein discovered diversity	1335:1365	the herein discovered diversity	1335:1365	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	5	4	dep	4-O-methyl-N-acetylglucosamine	763:792	arg1	e.g.					758:761	e.g.	758:761	e.g.	758:761	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	6	5	theme	phylogenetic	912:923	arg1	tree					925:928	a phylogenetic tree	910:928	a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns	910:1009	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns.
32031706	2	6	theme	products	365:372	arg1	structures					295:304	N-glycan structures	286:304	N-glycan structures of strain collection specimens and 80 commercial Chlorella products	286:372	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	8	7	theme	N-glycan	1260:1267	arg1	features					1280:1287	the almost identical N-glycan structural features	1239:1287	the almost identical N-glycan structural features that exist within vertebrates or land plants	1239:1332	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	6	8	theme	ITS1-5.8S-ITS2	868:881	arg1	sequences					888:896	barcode ITS1-5.8S-ITS2 rDNA sequences	860:896	barcode ITS1-5.8S-ITS2 rDNA sequences	860:896	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns.
32031706	5	9	theme	rare	716:719	arg1	types					721:725	different and rare types	702:725	different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine)	702:793	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	7	10	theme	fabulous	1066:1073	arg1	wealth					1075:1080	a fabulous wealth	1064:1080	a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes	1064:1224	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	2	11	theme	structures	295:304	arg1	survey					276:281	A mass spectrometry-based survey	250:281	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products	250:372	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	7	12	from	poor	1193:1196	arg1	attributes					1215:1224	morphological attributes	1201:1224	morphological attributes	1201:1224	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	6	13	theme	glycan	995:1000	arg1	patterns					1002:1009	glycan patterns	995:1009	glycan patterns	995:1009	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns.
32031706	0	14	from	diversity	43:51	arg1	microalgae					79:88	Chlorella microalgae	69:88	Chlorella microalgae	69:88	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.
32031706	5	15	theme	types	721:725	arg1	arabinose					688:696	arabinose	688:696	arabinose	688:696	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	2	16	theme	N-glycan	286:293	arg1	structures					295:304	N-glycan structures	286:304	N-glycan structures of strain collection specimens and 80 commercial Chlorella products	286:372	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	8	17	theme	identical	1250:1258	arg1	features					1280:1287	the almost identical N-glycan structural features	1239:1287	the almost identical N-glycan structural features that exist within vertebrates or land plants	1239:1332	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	8	18	theme	explicable	1423:1432	arg1	pressure					1409:1416	a selection pressure	1397:1416	a selection pressure only explicable	1397:1432	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	6	19	theme	sequences	888:896	arg1	Analysis					848:855	Analysis	848:855	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences	848:896	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns.
32031706	3	20	theme	glycan	561:566	arg1	masses					568:573	c. 100 different glycan masses	544:573	c. 100 different glycan masses	544:573	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	1	21	theme	fatty	163:167	arg1	production					174:183	fatty acid production	163:183	fatty acid production	163:183	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	8	22	theme	discovered	1346:1355	arg1	astonishing					1370:1380	astonishing	1370:1380	astonishing	1370:1380	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	8	22	theme	discovered	1346:1355	arg1	diversity					1357:1365	the herein discovered diversity	1335:1365	the herein discovered diversity	1335:1365	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	5	23	theme	arabinose	688:696	arg1	substitution					800:811	substitution	800:811	substitution of the second N-acetylglucosamine	800:845	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	5	23	theme	arabinose	688:696	arg1	occurrence					674:683	the occurrence	670:683	the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine)	670:793	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	6	24	theme	rDNA	883:886	arg1	sequences					888:896	barcode ITS1-5.8S-ITS2 rDNA sequences	860:896	barcode ITS1-5.8S-ITS2 rDNA sequences	860:896	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns.
32031706	1	25	theme	acid	169:172	arg1	production					174:183	fatty acid production	163:183	fatty acid production	163:183	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	0	26	theme	first	2:6	arg1	view					8:11	A first view	0:11	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.	0:89	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.
32031706	8	27	theme	structural	1269:1278	arg1	features					1280:1287	the almost identical N-glycan structural features	1239:1287	the almost identical N-glycan structural features that exist within vertebrates or land plants	1239:1332	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	7	28	theme	morphological	1201:1213	arg1	attributes					1215:1224	morphological attributes	1201:1224	morphological attributes	1201:1224	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	5	29	theme	second	820:825	arg1	N-acetylglucosamine					827:845	the second N-acetylglucosamine	816:845	the second N-acetylglucosamine	816:845	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	2	30	theme	specimens	327:335	arg1	structures					295:304	N-glycan structures	286:304	N-glycan structures of strain collection specimens and 80 commercial Chlorella products	286:372	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	2	31	theme	intragenus	401:410	arg1	diversity					412:420	a hitherto unseen intragenus diversity	383:420	a hitherto unseen intragenus diversity of N-glycan structures	383:443	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	6	32	from	hand	952:955	arg1	hand					960:963	hand	960:963	hand	960:963	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns.
32031706	4	33	theme	discernible	593:603	arg1	groups					617:622	Thirteen clearly discernible glycan-type groups	576:622	Thirteen clearly discernible glycan-type groups	576:622	Thirteen clearly discernible glycan-type groups were identified.
32031706	6	34	theme	barcode	860:866	arg1	sequences					888:896	barcode ITS1-5.8S-ITS2 rDNA sequences	860:896	barcode ITS1-5.8S-ITS2 rDNA sequences	860:896	Analysis of barcode ITS1-5.8S-ITS2 rDNA sequences established a phylogenetic tree that essentially went hand in hand with the grouping obtained by glycan patterns.
32031706	1	35	used	used	129:132	arg2	microalgae					101:110	Chlorella microalgae	91:110	Chlorella microalgae	91:110	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	8	36	theme	features	1280:1287	arg1	light					1230:1234	light	1230:1234	light of the almost identical N-glycan structural features that exist within vertebrates or land plants	1230:1332	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	2	37	theme	unseen	394:399	arg1	diversity					412:420	a hitherto unseen intragenus diversity	383:420	a hitherto unseen intragenus diversity of N-glycan structures	383:443	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	7	38	theme	brief	1017:1021	arg1	prelude					1023:1029	This brief prelude	1012:1029	This brief prelude to microalgal N-glycans	1012:1053	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	5	39	theme	Unexpected	641:650	arg1	features					652:659	Unexpected features	641:659	Unexpected features	641:659	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	2	40	theme	strain	309:314	arg1	specimens					327:335	strain collection specimens	309:335	strain collection specimens	309:335	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	1	41	theme	wastewater	186:195	arg1	processing					197:206	wastewater processing	186:206	wastewater processing	186:206	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	2	42	theme	collection	316:325	arg1	specimens					327:335	strain collection specimens	309:335	strain collection specimens	309:335	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	8	43	from	astonishing	1370:1380	arg1	light					1230:1234	light	1230:1234	light of the almost identical N-glycan structural features that exist within vertebrates or land plants	1230:1332	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	3	44	theme	c.	544:545	arg1	masses					568:573	c. 100 different glycan masses	544:573	c. 100 different glycan masses	544:573	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	8	45	theme	functional	1451:1460	arg1	role					1462:1465	a fundamental functional role	1437:1465	a fundamental functional role of these glycans	1437:1482	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	0	46	theme	unsuspected	20:30	arg1	diversity					43:51	the unsuspected intragenus diversity	16:51	the unsuspected intragenus diversity of N-glycans in Chlorella microalgae	16:88	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.
32031706	4	47	theme	glycan-type	605:615	arg1	groups					617:622	Thirteen clearly discernible glycan-type groups	576:622	Thirteen clearly discernible glycan-type groups	576:622	Thirteen clearly discernible glycan-type groups were identified.
32031706	1	48	dep	production	174:183	arg1	supplements					237:247	health-promoting food supplements	215:247	health-promoting food supplements	215:247	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	2	49	theme	structures	434:443	arg1	diversity					412:420	a hitherto unseen intragenus diversity	383:420	a hitherto unseen intragenus diversity of N-glycan structures	383:443	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	3	50	theme	methyl	467:472	arg1	N-acetylglucosamine					510:528	N-acetylglucosamine	510:528	N-acetylglucosamine	510:528	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	3	50	theme	methyl	467:472	arg1	pentoses					482:489	pentoses	482:489	pentoses	482:489	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	3	50	theme	methyl	467:472	arg1	groups					474:479	methyl groups	467:479	methyl groups	467:479	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	3	50	theme	methyl	467:472	arg1	deoxyhexoses					492:503	deoxyhexoses	492:503	deoxyhexoses	492:503	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	3	51	theme	Differing	446:454	arg1	numbers					456:462	Differing numbers	446:462	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine	446:528	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	8	52	theme	fundamental	1439:1449	arg1	role					1462:1465	a fundamental functional role	1437:1465	a fundamental functional role of these glycans	1437:1482	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	2	53	theme	N-glycan	425:432	arg1	structures					434:443	N-glycan structures	425:443	N-glycan structures	425:443	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	7	54	from	attributes	1215:1224	arg1	poor					1193:1196	poor	1193:1196	poor	1193:1196	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	7	55	theme	Chlorella-like	1144:1157	arg1	microalgae					1159:1168	Chlorella-like microalgae	1144:1168	Chlorella-like microalgae	1144:1168	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	2	56	theme	Chlorella	355:363	arg1	products					365:372	80 commercial Chlorella products	341:372	80 commercial Chlorella products	341:372	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	0	57	theme	intragenus	32:41	arg1	diversity					43:51	the unsuspected intragenus diversity	16:51	the unsuspected intragenus diversity of N-glycans in Chlorella microalgae	16:88	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.
32031706	5	58	theme	monosaccharide	730:743	arg1	methylation					745:755	monosaccharide methylation	730:755	monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine)	730:793	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	5	58	theme	monosaccharide	730:743	arg1	4-O-methyl-N-acetylglucosamine					763:792	4-O-methyl-N-acetylglucosamine	763:792	4-O-methyl-N-acetylglucosamine	763:792	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	7	59	theme	features	1108:1115	arg1	wealth					1075:1080	a fabulous wealth	1064:1080	a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes	1064:1224	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	2	60	theme	commercial	344:353	arg1	products					365:372	80 commercial Chlorella products	341:372	80 commercial Chlorella products	341:372	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	8	61	theme	land	1322:1325	arg1	plants					1327:1332	land plants	1322:1332	land plants	1322:1332	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	5	62	theme	methylation	745:755	arg1	types					721:725	different and rare types	702:725	different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine)	702:793	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	2	63	theme	spectrometry-based	257:274	arg1	survey					276:281	A mass spectrometry-based survey	250:281	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products	250:372	A mass spectrometry-based survey of N-glycan structures of strain collection specimens and 80 commercial Chlorella products revealed a hitherto unseen intragenus diversity of N-glycan structures.
32031706	8	64	theme	glycans	1476:1482	arg1	role					1462:1465	a fundamental functional role	1437:1465	a fundamental functional role of these glycans	1437:1482	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	7	65	theme	undescribed	1085:1095	arg1	features					1108:1115	undescribed structural features	1085:1115	undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes	1085:1224	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	7	66	theme	microalgal	1034:1043	arg1	N-glycans					1045:1053	microalgal N-glycans	1034:1053	microalgal N-glycans	1034:1053	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	1	67	theme	health-promoting	215:230	arg1	supplements					237:247	health-promoting food supplements	215:247	health-promoting food supplements	215:247	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	0	68	theme	N-glycans	56:64	arg1	diversity					43:51	the unsuspected intragenus diversity	16:51	the unsuspected intragenus diversity of N-glycans in Chlorella microalgae	16:88	A first view on the unsuspected intragenus diversity of N-glycans in Chlorella microalgae.
32031706	8	69	theme	selection	1399:1407	arg1	pressure					1409:1416	a selection pressure	1397:1416	a selection pressure only explicable	1397:1432	In light of the almost identical N-glycan structural features that exist within vertebrates or land plants, the herein discovered diversity is astonishing and argues for a selection pressure only explicable by a fundamental functional role of these glycans.
32031706	7	70	theme	structural	1097:1106	arg1	features					1108:1115	undescribed structural features	1085:1115	undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes	1085:1224	This brief prelude to microalgal N-glycans revealed a fabulous wealth of undescribed structural features that finely differentiated Chlorella-like microalgae, which are notoriously poor in morphological attributes.
32031706	1	71	theme	various	138:144	arg1	production					174:183	fatty acid production	163:183	fatty acid production	163:183	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	1	71	theme	various	138:144	arg1	purposes					146:153	various purposes	138:153	various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements	138:247	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	1	71	theme	various	138:144	arg1	processing					197:206	wastewater processing	186:206	wastewater processing	186:206	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	3	72	theme	groups	474:479	arg1	numbers					456:462	Differing numbers	446:462	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine	446:528	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32031706	1	73	theme	food	232:235	arg1	supplements					237:247	health-promoting food supplements	215:247	health-promoting food supplements	215:247	Chlorella microalgae are increasingly used for various purposes such as fatty acid production, wastewater processing, or as health-promoting food supplements.
32031706	5	74	theme	N-acetylglucosamine	827:845	arg1	substitution					800:811	substitution	800:811	substitution of the second N-acetylglucosamine	800:845	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	5	74	theme	N-acetylglucosamine	827:845	arg1	occurrence					674:683	the occurrence	670:683	the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine)	670:793	Unexpected features included the occurrence of arabinose, of different and rare types of monosaccharide methylation (e.g. 4-O-methyl-N-acetylglucosamine), and substitution of the second N-acetylglucosamine.
32031706	3	75	theme	different	551:559	arg1	masses					568:573	c. 100 different glycan masses	544:573	c. 100 different glycan masses	544:573	Differing numbers of methyl groups, pentoses, deoxyhexoses, and N-acetylglucosamine culminated in c. 100 different glycan masses.
32384234	3	0	theme	intact	770:775	arg1	glycopeptides					777:789	intact glycopeptides	770:789	intact glycopeptides largely performed in positive mode	770:824	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	6	1	theme	peptide	1408:1414	arg1	ion					1421:1423	the characteristic peptide core ion	1389:1423	the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1389:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	4	2	theme	fragmentation	937:949	arg1	pattern					951:957	the MS2 fragmentation pattern	929:957	the MS2 fragmentation pattern of glycopeptides in negative mode	929:991	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	5	3	theme	O-glycans	1164:1172	arg1	elimination					1137:1147	direct elimination	1130:1147	direct elimination of one or more O-glycans under negative-mode MS2	1130:1196	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	1	4	theme	glycoproteomic	229:242	arg1	undertakings					244:255	meaningful glycoproteomic undertakings	218:255	meaningful glycoproteomic undertakings	218:255	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	6	5	theme	cleavage	1441:1448	arg1	remnant					1450:1456	a ring cleavage remnant	1434:1456	a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1434:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	5	6	theme	negative-mode	1180:1192	arg1	MS2					1194:1196	negative-mode MS2	1180:1196	negative-mode MS2	1180:1196	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	7	7	theme	peptide	1764:1770	arg1	backbones					1772:1780	the same peptide backbones	1755:1780	the same peptide backbones	1755:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	3	8	theme	fragmentation	684:696	arg1	use					655:657	the use	651:657	the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode	651:824	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	7	9	theme	glycosylation	1738:1750	arg1	identification					1687:1700	definitive identification	1676:1700	definitive identification of single to multiple site-specific glycosylation on the same peptide backbones	1676:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	5	10	theme	dehydration	1322:1332	arg1	scars					1334:1338	the dehydration scars	1318:1338	the dehydration scars imprinted on the O-glycosylated sites	1318:1376	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	3	11	theme	negative-mode	662:674	arg1	fragmentation					684:696	negative-mode MS2/MS3 fragmentation	662:696	negative-mode MS2/MS3 fragmentation	662:696	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	1	12	theme	mass	182:185	arg1	MS					201:202	MS	201:202	MS	201:202	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	1	12	theme	mass	182:185	arg1	spectrometry					187:198	mass spectrometry	182:198	mass spectrometry (MS)	182:203	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	7	13	theme	biological	1857:1866	arg1	insights					1868:1875	structural and biological insights	1842:1875	structural and biological insights	1842:1875	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	2	14	gly	glycopeptides	460:472	arg2	glycopeptides					460:472	single glycopeptides	453:472	single glycopeptides	453:472	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	0	15	theme	Spectrometry-Based	85:102	arg1	Identification					104:117	Confident Mass Spectrometry-Based Identification	70:117	Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides	70:151	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	6	16	gly	N-glycopeptides	1555:1569	arg2	N-glycopeptides					1555:1569	all related N-glycopeptides	1543:1569	all related N-glycopeptides carrying additional O-glycans defined by specific mass increments	1543:1635	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	17	theme	amino	1475:1479	arg1	residue					1487:1493	the innermost amino sugar residue	1461:1493	the innermost amino sugar residue of an N-glycan	1461:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	17	theme	amino	1475:1479	arg1	N-glycan					1501:1508	an N-glycan	1498:1508	an N-glycan	1498:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	7	18	theme	structural	1842:1851	arg1	insights					1868:1875	structural and biological insights	1842:1875	structural and biological insights	1842:1875	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	7	19	theme	single	1705:1710	arg1	glycosylation					1738:1750	single to multiple site-specific glycosylation	1705:1750	single to multiple site-specific glycosylation on the same peptide backbones	1705:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	2	20	dep	de	376:377	arg1	novo					379:382	novo	379:382	novo	379:382	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	6	21	theme	sugar	1481:1485	arg1	residue					1487:1493	the innermost amino sugar residue	1461:1493	the innermost amino sugar residue of an N-glycan	1461:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	21	theme	sugar	1481:1485	arg1	N-glycan					1501:1508	an N-glycan	1498:1508	an N-glycan	1498:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	2	22	theme	practical	580:588	arg1	problems					590:597	practical problems	580:597	practical problems	580:597	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	2	23	gly	O-glycosylation	428:442	arg2	sites					444:448	multiple N- and O-glycosylation sites	412:448	multiple N- and O-glycosylation sites on single glycopeptides	412:472	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	0	24	theme	Glycosylated	131:142	arg1	Peptides					144:151	Multiple Glycosylated Peptides	122:151	Multiple Glycosylated Peptides	122:151	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	5	25	theme	easy	1209:1212	arg1	way					1214:1216	an easy way	1206:1216	an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites	1206:1376	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	2	26	theme	glycan	493:498	arg1	information					510:520	more glycan structure information	488:520	more glycan structure information	488:520	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	0	27	theme	Strategic	0:8	arg1	Applications					10:21	Strategic Applications	0:21	Strategic Applications of Negative-Mode LC-MS/MS Analyses	0:56	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	7	28	theme	significant	1807:1817	arg1	impact					1819:1824	a significant impact	1805:1824	a significant impact	1805:1824	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	7	29	from	identification	1687:1700	arg1	backbones					1772:1780	the same peptide backbones	1755:1780	the same peptide backbones	1755:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	0	30	theme	Confident	70:78	arg1	Identification					104:117	Confident Mass Spectrometry-Based Identification	70:117	Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides	70:151	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	3	31	theme	nanoLC-MS2-based	720:735	arg1	sequencing					737:746	current nanoLC-MS2-based sequencing	712:746	current nanoLC-MS2-based sequencing	712:746	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	2	32	theme	single	453:458	arg1	glycopeptides					460:472	single glycopeptides	453:472	single glycopeptides	453:472	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	0	33	theme	LC-MS/MS	40:47	arg1	Analyses					49:56	Negative-Mode LC-MS/MS Analyses	26:56	Negative-Mode LC-MS/MS Analyses	26:56	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	6	34	theme	N-glycan	1501:1508	arg1	residue					1487:1493	the innermost amino sugar residue	1461:1493	the innermost amino sugar residue of an N-glycan	1461:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	34	theme	N-glycan	1501:1508	arg1	N-glycan					1501:1508	an N-glycan	1498:1508	an N-glycan	1498:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	35	dep	filter	1532:1537	arg1	out					1539:1541	out	1539:1541	out	1539:1541	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	7	36	theme	Such	1638:1641	arg1	ability					1652:1658	Such enhanced ability	1638:1658	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones	1638:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	2	37	from	sites	444:448	arg1	glycopeptides					460:472	single glycopeptides	453:472	single glycopeptides	453:472	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	6	38	theme	specific	1612:1619	arg1	increments					1626:1635	specific mass increments	1612:1635	specific mass increments	1612:1635	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	1	39	theme	many	258:261	arg1	limitations					273:283	many technical limitations	258:283	many technical limitations	258:283	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	7	40	from	glycosylation	1738:1750	arg1	backbones					1772:1780	the same peptide backbones	1755:1780	the same peptide backbones	1755:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	2	41	theme	multiple	412:419	arg1	sites					444:448	multiple N- and O-glycosylation sites	412:448	multiple N- and O-glycosylation sites on single glycopeptides	412:472	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	6	42	theme	core	1416:1419	arg1	ion					1421:1423	the characteristic peptide core ion	1389:1423	the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1389:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	43	theme	additional	1580:1589	arg1	O-glycans					1591:1599	additional O-glycans	1580:1599	additional O-glycans defined by specific mass increments	1580:1635	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	4	44	theme	glycopeptides	962:974	arg1	pattern					951:957	the MS2 fragmentation pattern	929:957	the MS2 fragmentation pattern of glycopeptides in negative mode	929:991	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	3	45	theme	glycopeptides	777:789	arg1	identification					752:765	identification	752:765	identification	752:765	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	3	45	theme	glycopeptides	777:789	arg1	sequencing					737:746	current nanoLC-MS2-based sequencing	712:746	current nanoLC-MS2-based sequencing	712:746	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	6	46	theme	characteristic	1393:1406	arg1	ion					1421:1423	the characteristic peptide core ion	1389:1423	the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1389:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	4	47	from	program	1055:1061	arg1	moiety					1102:1107	the glycan moiety	1091:1107	the glycan moiety itself	1091:1114	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	4	48	theme	negative	979:986	arg1	mode					988:991	negative mode	979:991	negative mode	979:991	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	1	49	theme	technical	263:271	arg1	limitations					273:283	many technical limitations	258:283	many technical limitations	258:283	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	7	50	theme	insights	1868:1875	arg1	level					1833:1837	the level	1829:1837	the level of structural and biological insights	1829:1875	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	4	51	gly	glycopeptides	962:974	arg2	glycopeptides					962:974	glycopeptides	962:974	glycopeptides	962:974	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	4	52	theme	MS2	933:935	arg1	pattern					951:957	the MS2 fragmentation pattern	929:957	the MS2 fragmentation pattern of glycopeptides in negative mode	929:991	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	7	53	gly	glycosylation	1738:1750	arg1	backbones					1772:1780	the same peptide backbones	1755:1780	the same peptide backbones	1755:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	3	54	theme	positive	812:819	arg1	mode					821:824	positive mode	812:824	positive mode	812:824	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	2	55	theme	peptide	355:361	arg1	backbone					363:370	the peptide backbone	351:370	the peptide backbone	351:370	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	6	56	contain	carrying	1571:1578	arg1	N-glycopeptides					1555:1569	all related N-glycopeptides	1543:1569	all related N-glycopeptides carrying additional O-glycans defined by specific mass increments	1543:1635	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	56	contain	carrying	1571:1578	arg2	O-glycans					1591:1599	additional O-glycans	1580:1599	additional O-glycans defined by specific mass increments	1580:1635	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	7	57	theme	glycoproteomic	1893:1906	arg1	applications					1908:1919	glycoproteomic applications	1893:1919	glycoproteomic applications	1893:1919	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	1	58	theme	meaningful	218:227	arg1	undertakings					244:255	meaningful glycoproteomic undertakings	218:255	meaningful glycoproteomic undertakings	218:255	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	7	59	contain	have	1800:1803	arg2	impact					1819:1824	a significant impact	1805:1824	a significant impact	1805:1824	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	7	59	contain	have	1800:1803	arg1	ability					1652:1658	Such enhanced ability	1638:1658	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones	1638:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	7	60	theme	same	1759:1762	arg1	backbones					1772:1780	the same peptide backbones	1755:1780	the same peptide backbones	1755:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	6	61	theme	residue	1487:1493	arg1	remnant					1450:1456	a ring cleavage remnant	1434:1456	a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1434:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	62	theme	ring	1436:1439	arg1	remnant					1450:1456	a ring cleavage remnant	1434:1456	a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1434:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	4	63	with	Consistent	827:836	arg1	reports					852:858	previous reports	843:858	previous reports by others	843:868	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	3	64	theme	MS2/MS3	676:682	arg1	fragmentation					684:696	negative-mode MS2/MS3 fragmentation	662:696	negative-mode MS2/MS3 fragmentation	662:696	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	1	65	theme	recent	163:168	arg1	advances					170:177	recent advances	163:177	recent advances in mass spectrometry (MS)	163:203	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	7	66	theme	site-specific	1724:1736	arg1	glycosylation					1738:1750	single to multiple site-specific glycosylation	1705:1750	single to multiple site-specific glycosylation on the same peptide backbones	1705:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	4	67	theme	characteristic	1001:1014	arg1	features					1016:1023	the characteristic features	997:1023	the characteristic features identified	997:1034	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	0	68	theme	Mass	80:83	arg1	Identification					104:117	Confident Mass Spectrometry-Based Identification	70:117	Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides	70:151	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	7	69	dep	single	1705:1710	arg1	multiple					1715:1722	multiple	1715:1722	multiple	1715:1722	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	7	69	dep	single	1705:1710	arg1	to					1712:1713	to	1712:1713	to	1712:1713	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	4	70	theme	informative	1072:1082	arg1	MS3					1084:1086	the most informative MS3	1063:1086	the most informative MS3	1063:1086	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	5	71	gly	glycosylated	1272:1283	arg1	peptide					1285:1291	a multiply glycosylated peptide	1261:1291	a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites	1261:1376	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	7	72	dep	ability	1652:1658	arg1	advance					1663:1669	advance	1663:1669	to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones	1660:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	6	73	contain	carrying	1425:1432	arg1	ion					1421:1423	the characteristic peptide core ion	1389:1423	the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1389:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	73	contain	carrying	1425:1432	arg2	remnant					1450:1456	a ring cleavage remnant	1434:1456	a ring cleavage remnant of the innermost amino sugar residue of an N-glycan	1434:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	2	74	theme	isomeric	538:545	arg1	glycoforms					547:556	isomeric glycoforms	538:556	isomeric glycoforms	538:556	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	0	75	theme	Multiple	122:129	arg1	Peptides					144:151	Multiple Glycosylated Peptides	122:151	Multiple Glycosylated Peptides	122:151	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	7	76	theme	definitive	1676:1685	arg1	identification					1687:1700	definitive identification	1676:1700	definitive identification of single to multiple site-specific glycosylation on the same peptide backbones	1676:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	5	77	gly	O-glycosylated	1357:1370	arg1	sites					1372:1376	the O-glycosylated sites	1353:1376	the O-glycosylated sites	1353:1376	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	0	78	theme	Peptides	144:151	arg1	Identification					104:117	Confident Mass Spectrometry-Based Identification	70:117	Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides	70:151	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	4	79	from	pattern	951:957	arg1	mode					988:991	negative mode	979:991	negative mode	979:991	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	7	80	from	backbones	1772:1780	arg1	identification					1687:1700	definitive identification	1676:1700	definitive identification of single to multiple site-specific glycosylation on the same peptide backbones	1676:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	2	81	dep	delineating	400:410	arg1	sequence					342:349	sequence	342:349	sequence	342:349	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	2	82	theme	O-glycosylation	428:442	arg1	sites					444:448	multiple N- and O-glycosylation sites	412:448	multiple N- and O-glycosylation sites on single glycopeptides	412:472	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	6	83	theme	related	1547:1553	arg1	N-glycopeptides					1555:1569	all related N-glycopeptides	1543:1569	all related N-glycopeptides carrying additional O-glycans defined by specific mass increments	1543:1635	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	1	84	from	advances	170:177	arg1	MS					201:202	MS	201:202	MS	201:202	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	1	84	from	advances	170:177	arg1	spectrometry					187:198	mass spectrometry	182:198	mass spectrometry (MS)	182:203	Although recent advances in mass spectrometry (MS) have enabled meaningful glycoproteomic undertakings, many technical limitations remain unsolved.
32384234	2	85	theme	N-	421:422	arg1	sites					444:448	multiple N- and O-glycosylation sites	412:448	multiple N- and O-glycosylation sites on single glycopeptides	412:472	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	0	86	theme	Negative-Mode	26:38	arg1	Analyses					49:56	Negative-Mode LC-MS/MS Analyses	26:56	Negative-Mode LC-MS/MS Analyses	26:56	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	3	87	theme	current	712:718	arg1	sequencing					737:746	current nanoLC-MS2-based sequencing	712:746	current nanoLC-MS2-based sequencing	712:746	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	4	88	theme	previous	843:850	arg1	reports					852:858	previous reports	843:858	previous reports by others	843:868	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	0	89	theme	Analyses	49:56	arg1	Applications					10:21	Strategic Applications	0:21	Strategic Applications of Negative-Mode LC-MS/MS Analyses	0:56	Strategic Applications of Negative-Mode LC-MS/MS Analyses to Expedite Confident Mass Spectrometry-Based Identification of Multiple Glycosylated Peptides.
32384234	4	90	theme	glycan	1095:1100	arg1	moiety					1102:1107	the glycan moiety	1091:1107	the glycan moiety itself	1091:1114	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	6	91	theme	innermost	1465:1473	arg1	residue					1487:1493	the innermost amino sugar residue	1461:1493	the innermost amino sugar residue of an N-glycan	1461:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	6	91	theme	innermost	1465:1473	arg1	N-glycan					1501:1508	an N-glycan	1498:1508	an N-glycan	1498:1508	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	5	92	theme	direct	1130:1135	arg1	elimination					1137:1147	direct elimination	1130:1147	direct elimination of one or more O-glycans under negative-mode MS2	1130:1196	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	2	93	theme	structure	500:508	arg1	information					510:520	more glycan structure information	488:520	more glycan structure information	488:520	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	3	94	gly	glycopeptides	777:789	arg2	glycopeptides					777:789	intact glycopeptides	770:789	intact glycopeptides largely performed in positive mode	770:824	To address these issues, we explored the use of negative-mode MS2/MS3 fragmentation to supplement current nanoLC-MS2-based sequencing and identification of intact glycopeptides largely performed in positive mode.
32384234	2	95	theme	de	376:377	arg1	identification					384:397	de novo identification	376:397	de novo identification	376:397	Among these, the ability to efficiently sequence the peptide backbone for de novo identification, delineating multiple N- and O-glycosylation sites on single glycopeptides, and deriving more glycan structure information to discriminate isomeric glycoforms are well acknowledged practical problems to be tackled.
32384234	6	96	theme	mass	1621:1624	arg1	increments					1626:1635	specific mass increments	1612:1635	specific mass increments	1612:1635	Moreover, the characteristic peptide core ion carrying a ring cleavage remnant of the innermost amino sugar residue of an N-glycan can be relied upon to filter out all related N-glycopeptides carrying additional O-glycans defined by specific mass increments.
32384234	5	97	theme	glycosylated	1272:1283	arg1	peptide					1285:1291	a multiply glycosylated peptide	1261:1291	a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites	1261:1376	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
32384234	7	98	theme	enhanced	1643:1650	arg1	ability					1652:1658	Such enhanced ability	1638:1658	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones	1638:1780	Such enhanced ability to advance from definitive identification of single to multiple site-specific glycosylation on the same peptide backbones is anticipated to have a significant impact on the level of structural and biological insights one can gain in glycoproteomic applications.
32384234	4	99	used	utilized	1043:1050	arg2	features					1016:1023	the characteristic features	997:1023	the characteristic features identified	997:1034	Consistent with previous reports by others, we found that sulfation and sialylation drastically alter the MS2 fragmentation pattern of glycopeptides in negative mode and the characteristic features identified can be utilized to program the most informative MS3 on the glycan moiety itself.
32384234	5	100	theme	O-glycosylated	1357:1370	arg1	sites					1372:1376	the O-glycosylated sites	1353:1376	the O-glycosylated sites	1353:1376	Importantly, direct elimination of one or more O-glycans under negative-mode MS2 affords an easy way to discover additional O-glycosylations on a multiply glycosylated peptide by virtue of enumerating the dehydration scars imprinted on the O-glycosylated sites.
34254798	1	0	theme	core	185:188	arg1	glycans					201:207	sulfated core 2 O-GalNAc glycans	176:207	sulfated core 2 O-GalNAc glycans	176:207	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	0	1	theme	Glycans	88:94	arg1	Synthesis					34:42	Diversity-Oriented Chemoenzymatic Synthesis	0:42	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	0:94	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans.
34254798	3	2	with	branches	606:613	arg1	sequences					656:664	specifically designed glycosylation sequences	620:664	specifically designed glycosylation sequences	620:664	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	3	3	theme	divergent	439:447	arg1	extension					459:467	The divergent enzymatic extension	435:467	The divergent enzymatic extension	435:467	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	3	4	theme	designed	633:640	arg1	sequences					656:664	specifically designed glycosylation sequences	620:664	specifically designed glycosylation sequences	620:664	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	1	5	theme	O-GalNAc	192:199	arg1	glycans					201:207	sulfated core 2 O-GalNAc glycans	176:207	sulfated core 2 O-GalNAc glycans	176:207	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	3	6	theme	trisaccharides	482:495	arg1	extension					459:467	The divergent enzymatic extension	435:467	The divergent enzymatic extension	435:467	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	3	7	theme	glycosylation	642:654	arg1	sequences					656:664	specifically designed glycosylation sequences	620:664	specifically designed glycosylation sequences	620:664	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	1	8	theme	glycans	201:207	arg1	preparation					161:171	the collective preparation	146:171	the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts	146:242	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	0	9	theme	Chemoenzymatic	19:32	arg1	Synthesis					34:42	Diversity-Oriented Chemoenzymatic Synthesis	0:42	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	0:94	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans.
34254798	2	10	theme	group	376:380	arg1	manipulations					382:394	flexible protected group manipulations	357:394	flexible protected group manipulations	357:394	A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations.
34254798	0	11	theme	Diversity-Oriented	0:17	arg1	Synthesis					34:42	Diversity-Oriented Chemoenzymatic Synthesis	0:42	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	0:94	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans.
34254798	1	12	theme	diversity-oriented	99:116	arg1	approach					133:140	A diversity-oriented chemoenzymatic approach	97:140	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts	97:242	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	3	13	dep	extension	459:467	arg1	differentiating					586:600	differentiating	586:600	differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation	586:702	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	3	13	dep	extension	459:467	arg1	using					498:502	using	498:502	using a panel of robust glycosyltransferases that can recognize sulfated substrates	498:580	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	3	14	theme	enzymatic	449:457	arg1	extension					459:467	The divergent enzymatic extension	435:467	The divergent enzymatic extension	435:467	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	2	15	theme	flexible	357:364	arg1	manipulations					382:394	flexible protected group manipulations	357:394	flexible protected group manipulations	357:394	A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations.
34254798	1	16	theme	nonsulfated	219:229	arg1	counterparts					231:242	their nonsulfated counterparts	213:242	their nonsulfated counterparts	213:242	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	2	17	theme	protected	366:374	arg1	manipulations					382:394	flexible protected group manipulations	357:394	flexible protected group manipulations	357:394	A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations.
34254798	3	18	theme	regioselective	677:690	arg1	sialylation					692:702	regioselective sialylation	677:702	regioselective sialylation	677:702	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	1	19	theme	counterparts	231:242	arg1	preparation					161:171	the collective preparation	146:171	the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts	146:242	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	3	20	theme	glycosyltransferases	522:541	arg1	panel					506:510	a panel	504:510	a panel of robust glycosyltransferases that can recognize sulfated substrates	504:580	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	0	21	theme	Sulfated	47:54	arg1	Glycans					88:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans.
34254798	2	22	theme	sulfated	261:268	arg1	trisaccharide					270:282	A sulfated trisaccharide	259:282	A sulfated trisaccharide	259:282	A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations.
34254798	0	23	theme	Core	72:75	arg1	Glycans					88:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans.
34254798	2	24	theme	one-pot	411:417	arg1	glycosylations					419:432	sequential one-pot glycosylations	400:432	sequential one-pot glycosylations	400:432	A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations.
34254798	0	25	theme	Nonsulfated	60:70	arg1	Glycans					88:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans.
34254798	2	26	theme	sequential	400:409	arg1	glycosylations					419:432	sequential one-pot glycosylations	400:432	sequential one-pot glycosylations	400:432	A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations.
34254798	3	27	theme	well-defined	730:741	arg1	glycans					752:758	36 structurally well-defined O-GalNAc glycans	714:758	36 structurally well-defined O-GalNAc glycans	714:758	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	1	28	theme	collective	150:159	arg1	preparation					161:171	the collective preparation	146:171	the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts	146:242	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	1	29	theme	chemoenzymatic	118:131	arg1	approach					133:140	A diversity-oriented chemoenzymatic approach	97:140	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts	97:242	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
34254798	2	30	theme	nonsulfated	290:300	arg1	trisaccharide					302:314	a nonsulfated trisaccharide	288:314	a nonsulfated trisaccharide	288:314	A sulfated trisaccharide and a nonsulfated trisaccharide were chemically synthesized by combining flexible protected group manipulations and sequential one-pot glycosylations.
34254798	3	31	theme	sulfated	562:569	arg1	substrates					571:580	sulfated substrates	562:580	sulfated substrates	562:580	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	0	32	theme	O-GalNAc	79:86	arg1	Glycans					88:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Sulfated and Nonsulfated Core 2 O-GalNAc Glycans	47:94	Diversity-Oriented Chemoenzymatic Synthesis of Sulfated and Nonsulfated Core 2 O-GalNAc Glycans.
34254798	3	33	theme	O-GalNAc	743:750	arg1	glycans					752:758	36 structurally well-defined O-GalNAc glycans	714:758	36 structurally well-defined O-GalNAc glycans	714:758	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	3	34	theme	robust	515:520	arg1	glycosyltransferases					522:541	robust glycosyltransferases	515:541	robust glycosyltransferases that can recognize sulfated substrates	515:580	The divergent enzymatic extension of these two trisaccharides, using a panel of robust glycosyltransferases that can recognize sulfated substrates and differentiating the branches with specifically designed glycosylation sequences to achieve regioselective sialylation, provided 36 structurally well-defined O-GalNAc glycans.
34254798	1	35	theme	sulfated	176:183	arg1	glycans					201:207	sulfated core 2 O-GalNAc glycans	176:207	sulfated core 2 O-GalNAc glycans	176:207	A diversity-oriented chemoenzymatic approach for the collective preparation of sulfated core 2 O-GalNAc glycans and their nonsulfated counterparts was described.
32960038	7	0	theme	glycoforms	1717:1726	arg1	separation					1637:1646	high-resolution separation	1621:1646	high-resolution separation	1621:1646	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	0	theme	glycoforms	1717:1726	arg1	characterization					1663:1678	structural characterization	1652:1678	structural characterization	1652:1678	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	4	1	theme	diverse	986:992	arg1	range					994:998	a diverse range	984:998	a diverse range of hybrid and complex-type sialoglycoforms of fetuin	984:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	6	2	theme	sequencing	1214:1223	arg1	strategy					1225:1232	A glycan sequencing strategy	1205:1232	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues	1205:1317	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	3	3	theme	glycans	821:827	arg1	analyses					802:809	nanoflow LC-MS/MS analyses	784:809	nanoflow LC-MS/MS analyses of native glycans released from glycoproteins	784:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	7	4	theme	underivatized	1683:1695	arg1	regioisomers					1803:1814	regioisomers	1803:1814	regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1803:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	4	theme	underivatized	1683:1695	arg1	anomers					1761:1767	oligomannosidic glycan anomers	1738:1767	oligomannosidic glycan anomers	1738:1767	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	4	theme	underivatized	1683:1695	arg1	isomers					1790:1796	sialoglycan linkage isomers	1770:1796	sialoglycan linkage isomers	1770:1796	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	4	theme	underivatized	1683:1695	arg1	glycoforms					1717:1726	underivatized neutral and anionic glycoforms	1683:1726	underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1683:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	4	5	theme	ribonuclease	965:976	arg1	B					978:978	ribonuclease B	965:978	ribonuclease B	965:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	7	6	gly	fucosylated	1836:1846	arg1	sulfoglycans					1848:1859	afucosylated and fucosylated sulfoglycans	1819:1859	afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1819:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	6	7	theme	branching	1300:1308	arg1	residues					1310:1317	branching residues	1300:1317	branching residues	1300:1317	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	6	8	theme	isomeric	1396:1403	arg1	structures					1405:1414	closely related isomeric structures	1380:1414	closely related isomeric structures	1380:1414	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	4	9	theme	fetuin	1046:1051	arg1	hybrid					1003:1008	hybrid	1003:1008	hybrid	1003:1008	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	4	9	theme	fetuin	1046:1051	arg1	sialoglycoforms					1027:1041	complex-type sialoglycoforms	1014:1041	complex-type sialoglycoforms of fetuin	1014:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	7	10	gly	afucosylated	1819:1830	arg1	sulfoglycans					1848:1859	afucosylated and fucosylated sulfoglycans	1819:1859	afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1819:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	6	11	theme	specific	1288:1295	arg1	ions					1255:1258	diagnostic ions	1244:1258	diagnostic ions	1244:1258	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	5	12	theme	fragment	1190:1197	arg1	ions					1199:1202	the characteristic MS/MS fragment ions	1165:1202	the characteristic MS/MS fragment ions	1165:1202	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	6	13	theme	related	1388:1394	arg1	structures					1405:1414	closely related isomeric structures	1380:1414	closely related isomeric structures	1380:1414	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	1	14	theme	interpretation	457:470	arg1	lability					381:388	lability	381:388	lability of post-translational glycan modifications	381:431	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	14	theme	interpretation	457:470	arg1	composition					348:358	heterogeneous composition	334:358	heterogeneous composition	334:358	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	14	theme	interpretation	457:470	arg1	isomers					372:378	ubiquitous isomers	361:378	ubiquitous isomers	361:378	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	14	theme	interpretation	457:470	arg1	complexity					438:447	complexity	438:447	complexity of data interpretation	438:470	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	4	15	from	isomers	954:960	arg1	B					978:978	ribonuclease B	965:978	ribonuclease B	965:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	1	16	theme	analytical	248:257	arg1	challenge					259:267	an analytical challenge	245:267	an analytical challenge in large-scale glycomics applications	245:305	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	17	theme	sulfated-4-GalNAc	1894:1910	arg1	residues					1912:1919	sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1872:1919	sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1872:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	1	18	theme	structural	144:153	arg1	diversity					155:163	the structural diversity	140:163	the structural diversity of glycans	140:174	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	19	theme	sulfated-6-GlcNAc	1872:1888	arg1	residues					1912:1919	sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1872:1919	sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1872:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	4	20	theme	sialoglycoforms	1027:1041	arg1	range					994:998	a diverse range	984:998	a diverse range of hybrid and complex-type sialoglycoforms of fetuin	984:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	4	20	theme	sialoglycoforms	1027:1041	arg1	separation					912:921	highly resolved chromatographic separation	880:921	highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B	880:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	6	21	theme	data	1357:1360	arg1	interpretation					1362:1375	the MS/MS data interpretation	1347:1375	the MS/MS data interpretation of closely related isomeric structures	1347:1414	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	5	22	theme	characteristic	1169:1182	arg1	ions					1199:1202	the characteristic MS/MS fragment ions	1165:1202	the characteristic MS/MS fragment ions	1165:1202	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	3	23	theme	self-packed	720:730	arg1	columns					772:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	7	24	theme	sulfoglycans	1848:1859	arg1	regioisomers					1803:1814	regioisomers	1803:1814	regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1803:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	24	theme	sulfoglycans	1848:1859	arg1	anomers					1761:1767	oligomannosidic glycan anomers	1738:1767	oligomannosidic glycan anomers	1738:1767	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	24	theme	sulfoglycans	1848:1859	arg1	isomers					1790:1796	sialoglycan linkage isomers	1770:1796	sialoglycan linkage isomers	1770:1796	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	25	theme	native	1513:1518	arg1	sulfoglycans					1520:1531	native sulfoglycans	1513:1531	native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines	1513:1599	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	26	from	vaccines	1592:1599	arg1	sulfoglycans					1520:1531	native sulfoglycans	1513:1531	native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines	1513:1599	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	0	27	theme	Porous	60:65	arg1	Spectrometry					106:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	1	28	theme	lability	381:388	arg1	presence					322:329	the presence	318:329	the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation	318:470	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	4	29	from	separation	912:921	arg1	B					978:978	ribonuclease B	965:978	ribonuclease B	965:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	2	30	theme	glycan	647:652	arg1	identification					654:667	the comprehensive glycan identification	629:667	the comprehensive glycan identification	629:667	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	0	31	theme	Carbon	79:84	arg1	Spectrometry					106:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	1	32	theme	post-translational	393:410	arg1	modifications					419:431	post-translational glycan modifications	393:431	post-translational glycan modifications	393:431	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	33	theme	chromatography-tandem	186:206	arg1	LC-MS/MS					227:234	LC-MS/MS	227:234	LC-MS/MS	227:234	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	33	theme	chromatography-tandem	186:206	arg1	spectrometry					213:224	liquid chromatography-tandem mass spectrometry	179:224	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	179:235	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	34	theme	modifications	419:431	arg1	lability					381:388	lability	381:388	lability of post-translational glycan modifications	381:431	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	34	theme	modifications	419:431	arg1	composition					348:358	heterogeneous composition	334:358	heterogeneous composition	334:358	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	34	theme	modifications	419:431	arg1	isomers					372:378	ubiquitous isomers	361:378	ubiquitous isomers	361:378	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	34	theme	modifications	419:431	arg1	complexity					438:447	complexity	438:447	complexity of data interpretation	438:470	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	35	contain	containing	1861:1870	arg2	residues					1912:1919	sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1872:1919	sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1872:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	35	contain	containing	1861:1870	arg1	sulfoglycans					1848:1859	afucosylated and fucosylated sulfoglycans	1819:1859	afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1819:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	4	36	theme	resolved	887:894	arg1	separation					912:921	highly resolved chromatographic separation	880:921	highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B	880:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	5	37	theme	sialoglycan	1110:1120	arg1	isomers					1122:1128	linkage sialoglycan isomers	1102:1128	linkage sialoglycan isomers	1102:1128	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	7	38	from	egg-propagated	1542:1555	arg1	sulfoglycans					1520:1531	native sulfoglycans	1513:1531	native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines	1513:1599	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	2	39	theme	glycan	503:508	arg1	isomers					510:516	glycan isomers	503:516	glycan isomers differentiating from positional, linkage, branching, and anomeric structures	503:593	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	1	40	theme	heterogeneous	334:346	arg1	composition					348:358	heterogeneous composition	334:358	heterogeneous composition	334:358	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	41	theme	linkage	1782:1788	arg1	isomers					1790:1796	sialoglycan linkage isomers	1770:1796	sialoglycan linkage isomers	1770:1796	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	5	42	theme	anomeric	1081:1088	arg1	glycans					1090:1096	anomeric glycans	1081:1096	anomeric glycans	1081:1096	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	3	43	theme	carbon	759:764	arg1	columns					772:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	4	44	theme	high-mannose	934:945	arg1	isomers					954:960	over 20 high-mannose glycan isomers	926:960	over 20 high-mannose glycan isomers in ribonuclease B	926:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	0	45	theme	Native	33:38	arg1	Glycans					40:46	Native Glycans	33:46	Native Glycans	33:46	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	7	46	theme	glycome-wide	1462:1473	arg1	applications					1475:1486	glycome-wide applications	1462:1486	glycome-wide applications	1462:1486	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	3	47	theme	porous	742:747	arg1	columns					772:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	4	48	theme	isomers	954:960	arg1	range					994:998	a diverse range	984:998	a diverse range of hybrid and complex-type sialoglycoforms of fetuin	984:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	4	48	theme	isomers	954:960	arg1	separation					912:921	highly resolved chromatographic separation	880:921	highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B	880:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	1	49	theme	isomers	372:378	arg1	presence					322:329	the presence	318:329	the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation	318:470	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	50	theme	glycan	1754:1759	arg1	anomers					1761:1767	oligomannosidic glycan anomers	1738:1767	oligomannosidic glycan anomers	1738:1767	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	6	51	theme	diagnostic	1244:1253	arg1	ions					1255:1258	diagnostic ions	1244:1258	diagnostic ions	1244:1258	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	3	52	theme	PGC	767:769	arg1	columns					772:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	1	53	theme	large-scale	272:282	arg1	applications					294:305	large-scale glycomics applications	272:305	large-scale glycomics applications	272:305	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	54	theme	anionic	1709:1715	arg1	regioisomers					1803:1814	regioisomers	1803:1814	regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1803:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	54	theme	anionic	1709:1715	arg1	anomers					1761:1767	oligomannosidic glycan anomers	1738:1767	oligomannosidic glycan anomers	1738:1767	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	54	theme	anionic	1709:1715	arg1	isomers					1790:1796	sialoglycan linkage isomers	1770:1796	sialoglycan linkage isomers	1770:1796	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	54	theme	anionic	1709:1715	arg1	glycoforms					1717:1726	underivatized neutral and anionic glycoforms	1683:1726	underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1683:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	2	55	theme	comprehensive	633:645	arg1	identification					654:667	the comprehensive glycan identification	629:667	the comprehensive glycan identification	629:667	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	7	56	theme	neutral	1697:1703	arg1	regioisomers					1803:1814	regioisomers	1803:1814	regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1803:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	56	theme	neutral	1697:1703	arg1	anomers					1761:1767	oligomannosidic glycan anomers	1738:1767	oligomannosidic glycan anomers	1738:1767	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	56	theme	neutral	1697:1703	arg1	isomers					1790:1796	sialoglycan linkage isomers	1770:1796	sialoglycan linkage isomers	1770:1796	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	56	theme	neutral	1697:1703	arg1	glycoforms					1717:1726	underivatized neutral and anionic glycoforms	1683:1726	underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1683:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	6	57	theme	glycan	1207:1212	arg1	strategy					1225:1232	A glycan sequencing strategy	1205:1232	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues	1205:1317	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	3	58	theme	nanoflow	784:791	arg1	analyses					802:809	nanoflow LC-MS/MS analyses	784:809	nanoflow LC-MS/MS analyses of native glycans released from glycoproteins	784:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	7	59	theme	PGC-LC-MS/MS-based	1432:1449	arg1	method					1451:1456	the PGC-LC-MS/MS-based method	1428:1456	the PGC-LC-MS/MS-based method for glycome-wide applications	1428:1486	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	1	60	theme	mass	208:211	arg1	LC-MS/MS					227:234	LC-MS/MS	227:234	LC-MS/MS	227:234	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	60	theme	mass	208:211	arg1	spectrometry					213:224	liquid chromatography-tandem mass spectrometry	179:224	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	179:235	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	61	theme	structural	1652:1661	arg1	characterization					1663:1678	structural characterization	1652:1678	structural characterization	1652:1678	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	62	theme	high-resolution	1621:1635	arg1	separation					1637:1646	high-resolution separation	1621:1646	high-resolution separation	1621:1646	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	3	63	theme	native	814:819	arg1	glycans					821:827	native glycans	814:827	native glycans released from glycoproteins	814:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	6	64	theme	structures	1405:1414	arg1	interpretation					1362:1375	the MS/MS data interpretation	1347:1375	the MS/MS data interpretation of closely related isomeric structures	1347:1414	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	4	65	gly	sialoglycoforms	1027:1041	arg1	fetuin					1046:1051	fetuin	1046:1051	fetuin	1046:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	1	66	theme	data	452:455	arg1	interpretation					457:470	data interpretation	452:470	data interpretation	452:470	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	67	theme	culture-derived	1566:1580	arg1	vaccines					1592:1599	cell culture-derived influenza vaccines	1561:1599	cell culture-derived influenza vaccines	1561:1599	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	4	68	theme	hybrid	1003:1008	arg1	range					994:998	a diverse range	984:998	a diverse range of hybrid and complex-type sialoglycoforms of fetuin	984:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	4	68	theme	hybrid	1003:1008	arg1	separation					912:921	highly resolved chromatographic separation	880:921	highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B	880:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	1	69	from	challenge	259:267	arg1	applications					294:305	large-scale glycomics applications	272:305	large-scale glycomics applications	272:305	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	70	theme	diversity	155:163	arg1	Characterization					120:135	Characterization	120:135	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS)	120:235	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	71	theme	influenza	1582:1590	arg1	vaccines					1592:1599	cell culture-derived influenza vaccines	1561:1599	cell culture-derived influenza vaccines	1561:1599	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	7	72	theme	fucosylated	1836:1846	arg1	sulfoglycans					1848:1859	afucosylated and fucosylated sulfoglycans	1819:1859	afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1819:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	4	73	theme	complex-type	1014:1025	arg1	sialoglycoforms					1027:1041	complex-type sialoglycoforms	1014:1041	complex-type sialoglycoforms of fetuin	1014:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	6	74	theme	MS/MS	1351:1355	arg1	interpretation					1362:1375	the MS/MS data interpretation	1347:1375	the MS/MS data interpretation of closely related isomeric structures	1347:1414	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	7	75	dep	separation	1637:1646	arg1	the					1617:1619	the	1617:1619	the	1617:1619	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	0	76	theme	Graphitized	67:77	arg1	Spectrometry					106:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	5	77	theme	MS/MS	1184:1188	arg1	ions					1199:1202	the characteristic MS/MS fragment ions	1165:1202	the characteristic MS/MS fragment ions	1165:1202	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	3	78	theme	straightforward	691:705	arg1	method					707:712	a straightforward method	689:712	a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins	689:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	1	79	theme	glycans	168:174	arg1	diversity					155:163	the structural diversity	140:163	the structural diversity of glycans	140:174	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	80	theme	afucosylated	1819:1830	arg1	sulfoglycans					1848:1859	afucosylated and fucosylated sulfoglycans	1819:1859	afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues	1819:1919	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	2	81	theme	anomeric	575:582	arg1	structures					584:593	anomeric structures	575:593	anomeric structures	575:593	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	0	82	theme	Chromatography-Mass	86:104	arg1	Spectrometry					106:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	4	83	from	range	994:998	arg1	B					978:978	ribonuclease B	965:978	ribonuclease B	965:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	1	84	theme	liquid	179:184	arg1	LC-MS/MS					227:234	LC-MS/MS	227:234	LC-MS/MS	227:234	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	84	theme	liquid	179:184	arg1	spectrometry					213:224	liquid chromatography-tandem mass spectrometry	179:224	liquid chromatography-tandem mass spectrometry (LC-MS/MS)	179:235	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	1	85	theme	glycan	412:417	arg1	modifications					419:431	post-translational glycan modifications	393:431	post-translational glycan modifications	393:431	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	5	86	theme	glycans	1090:1096	arg1	α2,3					1131:1134	α2,3	1131:1134	α2,3	1131:1134	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	5	86	theme	glycans	1090:1096	arg1	structures					1067:1076	The distinct structures	1054:1076	The distinct structures of anomeric glycans and linkage sialoglycan isomers	1054:1128	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	5	86	theme	glycans	1090:1096	arg1	α2,6					1140:1143	α2,6	1140:1143	α2,6	1140:1143	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	4	87	from	B	978:978	arg1	range					994:998	a diverse range	984:998	a diverse range of hybrid and complex-type sialoglycoforms of fetuin	984:1051	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	4	87	from	B	978:978	arg1	separation					912:921	highly resolved chromatographic separation	880:921	highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B	880:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	5	88	theme	linkage	1102:1108	arg1	isomers					1122:1128	linkage sialoglycan isomers	1102:1128	linkage sialoglycan isomers	1102:1128	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	3	89	gly	glycoproteins	843:855	arg1	glycoproteins					843:855	glycoproteins	843:855	glycoproteins	843:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	0	90	theme	Isomeric	10:17	arg1	Structures					19:28	Isomeric Structures	10:28	Isomeric Structures of Native Glycans	10:46	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	1	91	theme	complexity	438:447	arg1	presence					322:329	the presence	318:329	the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation	318:470	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	5	92	theme	distinct	1058:1065	arg1	α2,3					1131:1134	α2,3	1131:1134	α2,3	1131:1134	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	5	92	theme	distinct	1058:1065	arg1	structures					1067:1076	The distinct structures	1054:1076	The distinct structures of anomeric glycans and linkage sialoglycan isomers	1054:1128	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	5	92	theme	distinct	1058:1065	arg1	α2,6					1140:1143	α2,6	1140:1143	α2,6	1140:1143	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	7	93	theme	cell	1561:1564	arg1	vaccines					1592:1599	cell culture-derived influenza vaccines	1561:1599	cell culture-derived influenza vaccines	1561:1599	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	2	94	theme	isomers	510:516	arg1	separation					489:498	High-resolution separation	473:498	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures	473:593	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	2	94	theme	isomers	510:516	arg1	prerequisite					606:617	a prerequisite	604:617	a prerequisite to ensure the comprehensive glycan identification	604:667	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	3	95	theme	graphitic	749:757	arg1	columns					772:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	0	96	theme	Glycans	40:46	arg1	Structures					19:28	Isomeric Structures	10:28	Isomeric Structures of Native Glycans	10:46	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	1	97	theme	composition	348:358	arg1	presence					322:329	the presence	318:329	the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation	318:470	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	3	98	theme	capillary	732:740	arg1	columns					772:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	self-packed capillary porous graphitic carbon (PGC) columns	720:778	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	2	99	theme	High-resolution	473:487	arg1	separation					489:498	High-resolution separation	473:498	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures	473:593	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	2	99	theme	High-resolution	473:487	arg1	prerequisite					606:617	a prerequisite	604:617	a prerequisite to ensure the comprehensive glycan identification	604:667	High-resolution separation of glycan isomers differentiating from positional, linkage, branching, and anomeric structures is often a prerequisite to ensure the comprehensive glycan identification.
32960038	0	100	theme	Nanoflow	51:58	arg1	Spectrometry					106:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry	51:117	Resolving Isomeric Structures of Native Glycans by Nanoflow Porous Graphitized Carbon Chromatography-Mass Spectrometry.
32960038	1	101	theme	ubiquitous	361:370	arg1	isomers					372:378	ubiquitous isomers	361:378	ubiquitous isomers	361:378	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32960038	7	102	theme	sialoglycan	1770:1780	arg1	isomers					1790:1796	sialoglycan linkage isomers	1770:1796	sialoglycan linkage isomers	1770:1796	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	6	103	theme	complementary	1264:1276	arg1	fragments					1278:1286	complementary fragments	1264:1286	complementary fragments	1264:1286	A glycan sequencing strategy utilizing diagnostic ions and complementary fragments specific to branching residues was established to simplify the MS/MS data interpretation of closely related isomeric structures.
32960038	7	104	link	culture-derived	1566:1580	arg1	vaccines					1592:1599	cell culture-derived influenza vaccines	1561:1599	cell culture-derived influenza vaccines	1561:1599	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	4	105	theme	glycan	947:952	arg1	isomers					954:960	over 20 high-mannose glycan isomers	926:960	over 20 high-mannose glycan isomers in ribonuclease B	926:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	5	106	theme	isomers	1122:1128	arg1	α2,3					1131:1134	α2,3	1131:1134	α2,3	1131:1134	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	5	106	theme	isomers	1122:1128	arg1	structures					1067:1076	The distinct structures	1054:1076	The distinct structures of anomeric glycans and linkage sialoglycan isomers	1054:1128	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	5	106	theme	isomers	1122:1128	arg1	α2,6					1140:1143	α2,6	1140:1143	α2,6	1140:1143	The distinct structures of anomeric glycans and linkage sialoglycan isomers, α2,3 and α2,6, were identified by the characteristic MS/MS fragment ions.
32960038	4	107	theme	chromatographic	896:910	arg1	separation					912:921	highly resolved chromatographic separation	880:921	highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B	880:978	The technique enables highly resolved chromatographic separation of over 20 high-mannose glycan isomers in ribonuclease B and a diverse range of hybrid and complex-type sialoglycoforms of fetuin.
32960038	3	108	attach	released	829:836	arg2	glycans					821:827	native glycans	814:827	native glycans released from glycoproteins	814:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	3	108	attach	released	829:836	arg1	glycoproteins					843:855	glycoproteins	843:855	glycoproteins	843:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	7	109	theme	oligomannosidic	1738:1752	arg1	anomers					1761:1767	oligomannosidic glycan anomers	1738:1767	oligomannosidic glycan anomers	1738:1767	To promote the PGC-LC-MS/MS-based method for glycome-wide applications, we extended analyses to native sulfoglycans from the egg-propagated and cell culture-derived influenza vaccines and demonstrate the high-resolution separation and structural characterization of underivatized neutral and anionic glycoforms including oligomannosidic glycan anomers, sialoglycan linkage isomers, and regioisomers of afucosylated and fucosylated sulfoglycans containing sulfated-6-GlcNAc and sulfated-4-GalNAc residues.
32960038	3	110	theme	LC-MS/MS	793:800	arg1	analyses					802:809	nanoflow LC-MS/MS analyses	784:809	nanoflow LC-MS/MS analyses of native glycans released from glycoproteins	784:855	Here, we developed a straightforward method using self-packed capillary porous graphitic carbon (PGC) columns for nanoflow LC-MS/MS analyses of native glycans released from glycoproteins.
32960038	1	111	theme	glycomics	284:292	arg1	applications					294:305	large-scale glycomics applications	272:305	large-scale glycomics applications	272:305	Characterization of the structural diversity of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an analytical challenge in large-scale glycomics applications because of the presence of heterogeneous composition, ubiquitous isomers, lability of post-translational glycan modifications, and complexity of data interpretation.
32887075	6	0	theme	signal	1069:1074	arg1	strength					1076:1083	the signal strength	1065:1083	the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry	1065:1152	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	6	0	theme	signal	1069:1074	arg1	higher					1172:1177	higher	1172:1177	higher	1172:1177	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	10	1	theme	oligomannose	1864:1875	arg1	understanding					1839:1851	the evolutionary understanding	1822:1851	the evolutionary understanding of the IgM oligomannose modification and function	1822:1901	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	8	2	with	complex-type	1427:1438	arg1	content					1451:1457	a low content	1445:1457	a low content of fucosylation	1445:1473	N-glycans in other sites were mainly complex-type with a low content of fucosylation and sialylated.
32887075	5	3	from	sites	948:952	arg1	domain					912:917	the CH3 domain	904:917	the CH3 domain	904:917	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	3	from	sites	948:952	arg1	domain					965:970	the CH4 domain	957:970	the CH4 domain	957:970	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	3	from	sites	948:952	arg1	chain					833:837	O.niloticus IgM heavy chain	811:837	O.niloticus IgM heavy chain	811:837	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	3	from	sites	948:952	arg1	domain					876:881	the CH2 domain	868:881	the CH2 domain	868:881	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	9	4	from	oligomannose	1495:1506	arg1	IgM					1524:1526	TNP-specific IgM	1511:1526	TNP-specific IgM	1511:1526	The oligomannose in TNP-specific IgM was further verified to be essential for the binding of IgM and MBL.
32887075	7	5	theme	site	1384:1387	arg1	IgM					1372:1374	the PBS-immunized IgM	1354:1374	the PBS-immunized IgM of this site	1354:1387	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	4	6	used	used	570:573	arg2	methods					551:557	These methods	545:557	These methods	545:557	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	10	7	theme	chain	1722:1726	arg1	modification					1684:1695	the site-specific oligomannose modification	1653:1695	the site-specific oligomannose modification of O.niloticus IgM heavy chain	1653:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	6	8	theme	mass	1136:1139	arg1	spectrometry					1141:1152	primary mass spectrometry	1128:1152	primary mass spectrometry	1128:1152	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	7	9	theme	PBS-immunized	1358:1370	arg1	IgM					1372:1374	the PBS-immunized IgM	1354:1374	the PBS-immunized IgM of this site	1354:1387	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	2	10	theme	immunoglobulin	293:306	arg1	glycosylation					308:320	teleost immunoglobulin glycosylation	285:320	teleost immunoglobulin glycosylation	285:320	While, the study on teleost immunoglobulin glycosylation is still limitted.
32887075	8	11	theme	other	1403:1407	arg1	sites					1409:1413	other sites	1403:1413	other sites	1403:1413	N-glycans in other sites were mainly complex-type with a low content of fucosylation and sialylated.
32887075	1	12	from	structure	211:219	arg1	mammals					256:262	mammals	256:262	mammals	256:262	N-glycan modification is reported to be important in regulating the structure and function of immunoglobulins in mammals.
32887075	5	13	from	sites	802:806	arg1	domain					912:917	the CH3 domain	904:917	the CH3 domain	904:917	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	13	from	sites	802:806	arg1	domain					965:970	the CH4 domain	957:970	the CH4 domain	957:970	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	13	from	sites	802:806	arg1	chain					833:837	O.niloticus IgM heavy chain	811:837	O.niloticus IgM heavy chain	811:837	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	13	from	sites	802:806	arg1	domain					876:881	the CH2 domain	868:881	the CH2 domain	868:881	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	2	14	from	study	276:280	arg1	glycosylation					308:320	teleost immunoglobulin glycosylation	285:320	teleost immunoglobulin glycosylation	285:320	While, the study on teleost immunoglobulin glycosylation is still limitted.
32887075	7	15	theme	small	1312:1316	arg1	oligomannose					1328:1339	oligomannose	1328:1339	oligomannose	1328:1339	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	7	15	theme	small	1312:1316	arg1	amount					1318:1323	only a small amount	1305:1323	only a small amount of oligomannose	1305:1339	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	5	16	theme	N-glycosylation	786:800	arg1	sites					802:806	four N-glycosylation sites	781:806	four N-glycosylation sites	781:806	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	4	17	theme	specific	727:734	arg1	antigen					736:742	specific antigen	727:742	specific antigen	727:742	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	8	18	theme	fucosylation	1462:1473	arg1	content					1451:1457	a low content	1445:1457	a low content of fucosylation	1445:1473	N-glycans in other sites were mainly complex-type with a low content of fucosylation and sialylated.
32887075	3	19	dep	driven	385:390	arg1	TNP-antigen					373:383	TNP-antigen	373:383	TNP-antigen	373:383	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	5	20	gly	N-glycosylation	786:800	arg2	sites					802:806	four N-glycosylation sites	781:806	four N-glycosylation sites	781:806	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	20	gly	N-glycosylation	786:800	arg2	four					781:784	four	781:784	four	781:784	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	9	21	theme	TNP-specific	1511:1522	arg1	IgM					1524:1526	TNP-specific IgM	1511:1526	TNP-specific IgM	1511:1526	The oligomannose in TNP-specific IgM was further verified to be essential for the binding of IgM and MBL.
32887075	0	22	theme	modification	43:54	arg1	detection					17:25	Relative content detection	0:25	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.	0:141	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	5	23	theme	CH4	961:963	arg1	domain					965:970	the CH4 domain	957:970	the CH4 domain	957:970	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	3	24	theme	driven	385:390	arg1	model					392:396	a TNP-antigen driven model	371:396	a TNP-antigen driven model	371:396	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	3	25	theme	site-specific	416:428	arg1	N-glycans					430:438	the site-specific N-glycans	412:438	the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS	412:542	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	0	26	theme	Relative	0:7	arg1	detection					17:25	Relative content detection	0:25	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.	0:141	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	5	27	theme	Asn-509	928:934	arg1	sites					948:952	the Asn-509 and Asn-551 sites	924:952	sites	948:952	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	6	28	from	IgM	1121:1123	arg1	spectrometry					1141:1152	primary mass spectrometry	1128:1152	primary mass spectrometry	1128:1152	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	3	29	theme	Oreochromis	474:484	arg1	niloticus					486:494	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	5	30	theme	Asn-551	940:946	arg1	sites					948:952	the Asn-509 and Asn-551 sites	924:952	sites	948:952	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	31	theme	Asn-338	888:894	arg1	site					896:899	the Asn-338 site	884:899	the Asn-338 site in the CH3 domain	884:917	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	0	32	theme	oligomannose	30:41	arg1	modification					43:54	oligomannose modification	30:54	oligomannose modification	30:54	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	5	33	theme	IgM	823:825	arg1	chain					833:837	O.niloticus IgM heavy chain	811:837	O.niloticus IgM heavy chain	811:837	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	0	34	theme	heavy	63:67	arg1	chain					69:73	IgM heavy chain	59:73	IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS	59:140	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	1	35	dep	structure	211:219	arg1	the					207:209	the	207:209	the	207:209	N-glycan modification is reported to be important in regulating the structure and function of immunoglobulins in mammals.
32887075	3	36	theme	serum	496:500	arg1	IgM					502:504	serum IgM	496:504	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	9	37	theme	IgM	1584:1586	arg1	binding					1573:1579	the binding	1569:1579	the binding of IgM and MBL	1569:1594	The oligomannose in TNP-specific IgM was further verified to be essential for the binding of IgM and MBL.
32887075	6	38	theme	oligomannose	1088:1099	arg1	strength					1076:1083	the signal strength	1065:1083	the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry	1065:1152	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	6	38	theme	oligomannose	1088:1099	arg1	higher					1172:1177	higher	1172:1177	higher	1172:1177	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	10	39	theme	evolutionary	1826:1837	arg1	understanding					1839:1851	the evolutionary understanding	1822:1851	the evolutionary understanding of the IgM oligomannose modification and function	1822:1901	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	10	40	theme	heavy	1716:1720	arg1	chain					1722:1726	O.niloticus IgM heavy chain	1700:1726	O.niloticus IgM heavy chain	1700:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	1	41	theme	immunoglobulins	237:251	arg1	function					225:232	function	225:232	function	225:232	N-glycan modification is reported to be important in regulating the structure and function of immunoglobulins in mammals.
32887075	1	41	theme	immunoglobulins	237:251	arg1	structure					211:219	structure	211:219	structure	211:219	N-glycan modification is reported to be important in regulating the structure and function of immunoglobulins in mammals.
32887075	0	42	theme	IgM	59:61	arg1	chain					69:73	IgM heavy chain	59:73	IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS	59:140	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	9	43	theme	MBL	1592:1594	arg1	binding					1573:1579	the binding	1569:1579	the binding of IgM and MBL	1569:1594	The oligomannose in TNP-specific IgM was further verified to be essential for the binding of IgM and MBL.
32887075	5	44	gly	N-glycosylated	1015:1028	arg1	All					973:975	All	973:975	All	973:975	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	44	gly	N-glycosylated	1015:1028	arg1	residues					989:996	the four residues	980:996	the four residues	980:996	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	6	45	from	strength	1076:1083	arg1	IgM					1121:1123	the TNP-specific IgM	1104:1123	the TNP-specific IgM in primary mass spectrometry	1104:1152	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	10	46	theme	O.niloticus	1700:1710	arg1	chain					1722:1726	O.niloticus IgM heavy chain	1700:1726	O.niloticus IgM heavy chain	1700:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	4	47	theme	protein	602:608	arg1	modification					610:621	protein modification	602:621	protein modification	602:621	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	10	48	theme	IgM	1860:1862	arg1	oligomannose					1864:1875	the IgM oligomannose modification and function	1856:1901	the IgM oligomannose modification and function	1856:1901	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	2	49	theme	teleost	285:291	arg1	glycosylation					308:320	teleost immunoglobulin glycosylation	285:320	teleost immunoglobulin glycosylation	285:320	While, the study on teleost immunoglobulin glycosylation is still limitted.
32887075	7	50	located	found	1345:1349	arg2	oligomannose					1328:1339	oligomannose	1328:1339	oligomannose	1328:1339	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	7	50	located	found	1345:1349	arg1	IgM					1372:1374	the PBS-immunized IgM	1354:1374	the PBS-immunized IgM of this site	1354:1387	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	7	50	located	found	1345:1349	arg2	amount					1318:1323	only a small amount	1305:1323	only a small amount of oligomannose	1305:1339	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	6	51	theme	TNP-specific	1108:1119	arg1	IgM					1121:1123	the TNP-specific IgM	1104:1123	the TNP-specific IgM in primary mass spectrometry	1104:1152	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	5	52	theme	CH2	872:874	arg1	domain					876:881	the CH2 domain	868:881	the CH2 domain	868:881	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	4	53	theme	N-glycosylation	681:695	arg1	level					672:676	the level	668:676	the level of N-glycosylation	668:695	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	6	54	theme	primary	1128:1134	arg1	spectrometry					1141:1152	primary mass spectrometry	1128:1152	primary mass spectrometry	1128:1152	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	4	55	theme	teleost	700:706	arg1	Igs					708:710	teleost Igs	700:710	teleost Igs that driven by specific antigen	700:742	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	4	56	used	used	650:653	arg2	methods					551:557	These methods	545:557	These methods	545:557	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	10	57	theme	important	1743:1751	arg1	role					1753:1756	an important role	1740:1756	an important role	1740:1756	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	8	58	from	N-glycans	1390:1398	arg1	sites					1409:1413	other sites	1403:1413	other sites	1403:1413	N-glycans in other sites were mainly complex-type with a low content of fucosylation and sialylated.
32887075	5	59	theme	Asn-315	852:858	arg1	site					860:863	the Asn-315 site	848:863	the Asn-315 site in the CH2 domain	848:881	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	1	60	theme	N-glycan	143:150	arg1	modification					152:163	N-glycan modification	143:163	N-glycan modification	143:163	N-glycan modification is reported to be important in regulating the structure and function of immunoglobulins in mammals.
32887075	10	61	theme	IgM	1780:1782	arg1	interaction					1765:1775	the interaction	1761:1775	the interaction	1761:1775	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	10	62	mod	modification	1684:1695	arg1	chain					1722:1726	O.niloticus IgM heavy chain	1700:1726	O.niloticus IgM heavy chain	1700:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	10	62	mod	modification	1684:1695	arg3	oligomannose					1671:1682	the site-specific oligomannose modification	1653:1695	the site-specific oligomannose modification of O.niloticus IgM heavy chain	1653:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	5	63	theme	CH3	908:910	arg1	domain					912:917	the CH3 domain	904:917	the CH3 domain	904:917	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	6	64	theme	PBS-immunized	1196:1208	arg1	IgM					1210:1212	the PBS-immunized IgM	1192:1212	the PBS-immunized IgM	1192:1212	After immunized with TNP-antigen, the signal strength of oligomannose in the TNP-specific IgM in primary mass spectrometry was significantly higher than that in the PBS-immunized IgM.
32887075	1	65	from	function	225:232	arg1	mammals					256:262	mammals	256:262	mammals	256:262	N-glycan modification is reported to be important in regulating the structure and function of immunoglobulins in mammals.
32887075	5	66	from	site	860:863	arg1	domain					912:917	the CH3 domain	904:917	the CH3 domain	904:917	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	66	from	site	860:863	arg1	domain					965:970	the CH4 domain	957:970	the CH4 domain	957:970	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	66	from	site	860:863	arg1	chain					833:837	O.niloticus IgM heavy chain	811:837	O.niloticus IgM heavy chain	811:837	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	66	from	site	860:863	arg1	domain					876:881	the CH2 domain	868:881	the CH2 domain	868:881	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	8	67	theme	low	1447:1449	arg1	content					1451:1457	a low content	1445:1457	a low content of fucosylation	1445:1473	N-glycans in other sites were mainly complex-type with a low content of fucosylation and sialylated.
32887075	7	68	theme	oligomannose	1328:1339	arg1	oligomannose					1328:1339	oligomannose	1328:1339	oligomannose	1328:1339	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	7	68	theme	oligomannose	1328:1339	arg1	amount					1318:1323	only a small amount	1305:1323	only a small amount of oligomannose	1305:1339	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	10	69	theme	site-specific	1657:1669	arg1	modification					1684:1695	the site-specific oligomannose modification	1653:1695	the site-specific oligomannose modification of O.niloticus IgM heavy chain	1653:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	0	70	theme	chain	69:73	arg1	detection					17:25	Relative content detection	0:25	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.	0:141	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	10	71	theme	MBL	1788:1790	arg1	interaction					1765:1775	the interaction	1761:1775	the interaction	1761:1775	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	8	72	gly	sialylated	1479:1488	arg1	N-glycans					1390:1398	N-glycans	1390:1398	N-glycans in other sites	1390:1413	N-glycans in other sites were mainly complex-type with a low content of fucosylation and sialylated.
32887075	0	73	theme	early	104:108	arg1	vertebrate					110:119	an early vertebrate	101:119	an early vertebrate through nanoLC-MS/MS	101:140	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	4	74	dep	enrichment	587:596	arg1	identification					623:636	identification	623:636	identification	623:636	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	5	75	from	site	896:899	arg1	domain					912:917	the CH3 domain	904:917	the CH3 domain	904:917	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	75	from	site	896:899	arg1	domain					965:970	the CH4 domain	957:970	the CH4 domain	957:970	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	75	from	site	896:899	arg1	chain					833:837	O.niloticus IgM heavy chain	811:837	O.niloticus IgM heavy chain	811:837	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	5	75	from	site	896:899	arg1	domain					876:881	the CH2 domain	868:881	the CH2 domain	868:881	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	3	76	theme	PBS-immunized	443:455	arg1	niloticus					486:494	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	0	77	theme	content	9:15	arg1	detection					17:25	Relative content detection	0:25	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.	0:141	Relative content detection of oligomannose modification of IgM heavy chain induced by TNP-antigen in an early vertebrate through nanoLC-MS/MS.
32887075	7	78	contain	had	1245:1247	arg2	site					1260:1263	an Asn-509 site	1249:1263	an Asn-509 site fully occupied with oligomannose	1249:1296	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	7	78	contain	had	1245:1247	arg1	IgM					1241:1243	the TNP-specific IgM	1224:1243	the TNP-specific IgM	1224:1243	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	4	79	theme	peptide	579:585	arg1	enrichment					587:596	peptide enrichment	579:596	peptide enrichment	579:596	These methods are widely used for peptide enrichment and protein modification identification, but rarely used in detecting the level of N-glycosylation in teleost Igs that driven by specific antigen.
32887075	3	80	theme	niloticus	486:494	arg1	N-glycans					430:438	the site-specific N-glycans	412:438	the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS	412:542	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	5	81	theme	O.niloticus	811:821	arg1	chain					833:837	O.niloticus IgM heavy chain	811:837	O.niloticus IgM heavy chain	811:837	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	10	82	dep	oligomannose	1864:1875	arg1	modification					1877:1888	modification	1877:1888	modification	1877:1888	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	10	82	dep	oligomannose	1864:1875	arg1	function					1894:1901	function	1894:1901	function	1894:1901	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	3	83	theme	TNP-specific	461:472	arg1	niloticus					486:494	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	5	84	theme	heavy	827:831	arg1	chain					833:837	O.niloticus IgM heavy chain	811:837	O.niloticus IgM heavy chain	811:837	The results revealed that there are four N-glycosylation sites in O.niloticus IgM heavy chain, namely, the Asn-315 site in the CH2 domain, the Asn-338 site in the CH3 domain, and the Asn-509 and Asn-551 sites in the CH4 domain, All of the four residues were efficiently N-glycosylated.
32887075	7	85	theme	Asn-509	1252:1258	arg1	site					1260:1263	an Asn-509 site	1249:1263	an Asn-509 site fully occupied with oligomannose	1249:1296	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	10	86	theme	oligomannose	1671:1682	arg1	modification					1684:1695	the site-specific oligomannose modification	1653:1695	the site-specific oligomannose modification of O.niloticus IgM heavy chain	1653:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32887075	3	87	dep	niloticus	486:494	arg1	IgM					502:504	serum IgM	496:504	PBS-immunized and TNP-specific Oreochromis niloticus serum IgM	443:504	In this study, we constructed a TNP-antigen driven model, and detected the site-specific N-glycans of PBS-immunized and TNP-specific Oreochromis niloticus serum IgM through 18O-labeling and nanoLC-MS/MS.
32887075	7	88	theme	TNP-specific	1228:1239	arg1	IgM					1241:1243	the TNP-specific IgM	1224:1243	the TNP-specific IgM	1224:1243	Notably, the TNP-specific IgM had an Asn-509 site fully occupied with oligomannose, while only a small amount of oligomannose was found in the PBS-immunized IgM of this site.
32887075	10	89	theme	IgM	1712:1714	arg1	chain					1722:1726	O.niloticus IgM heavy chain	1700:1726	O.niloticus IgM heavy chain	1700:1726	These results demonstrated that the TNP-antigen induced the site-specific oligomannose modification of O.niloticus IgM heavy chain, and played an important role in the interaction of IgM and MBL, which provided insights into the evolutionary understanding of the IgM oligomannose modification and function.
32627435	6	0	theme	fucosylated	1246:1256	arg1	structures					1258:1267	fucosylated structures	1246:1267	fucosylated structures with impact coefficient in the range of 0.1-0.2	1246:1315	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	1	theme	/Gal	1179:1182	arg1	%					1183:1183	ADCC%/Gal%	1174:1183	ADCC%/Gal%	1174:1183	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	1	theme	/Gal	1179:1182	arg1	coefficients					1160:1171	impact coefficients	1153:1171	impact coefficients (ADCC%/Gal%) more than 20	1153:1197	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	3	2	theme	terminal	570:577	arg1	galactosylation					579:593	terminal galactosylation	570:593	terminal galactosylation of an IgG1	570:604	However, whether terminal galactosylation of an IgG1 impacts its ADCC activity is less understood.
32627435	1	3	theme	therapeutic	304:314	arg1	IgG1					333:336	IgG1	333:336	IgG1	333:336	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	3	theme	therapeutic	304:314	arg1	G1					329:330	therapeutic immunoglobin G1	304:330	some therapeutic immunoglobin G1 (IgG1) antibodies	299:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	7	4	theme	effector	1447:1454	arg1	function					1456:1463	effector function	1447:1463	effector function for efficacy	1447:1476	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	6	5	theme	ADCC	1174:1177	arg1	%					1183:1183	ADCC%/Gal%	1174:1183	ADCC%/Gal%	1174:1183	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	5	theme	ADCC	1174:1177	arg1	coefficients					1160:1171	impact coefficients	1153:1171	impact coefficients (ADCC%/Gal%) more than 20	1153:1197	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	4	6	theme	new	668:670	arg1	strategy					672:679	a new strategy	666:679	a new strategy for glycan enrichment and remodeling	666:716	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	6	7	theme	minimal	1208:1214	arg1	influence					1216:1224	minimal influence	1208:1224	minimal influence on ADCC activity	1208:1241	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	3	8	theme	IgG1	601:604	arg1	galactosylation					579:593	terminal galactosylation	570:593	terminal galactosylation of an IgG1	570:604	However, whether terminal galactosylation of an IgG1 impacts its ADCC activity is less understood.
32627435	2	9	from	levels	392:397	arg1	region					452:457	the Fc region	445:457	the Fc region	445:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	5	10	theme	structure	1055:1063	arg1	residue					1013:1019	the first N-acetyl glucosamine residue	982:1019	the first N-acetyl glucosamine residue of an N-linked glycosylation core structure	982:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	10	theme	structure	1055:1063	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	11	theme	influence	840:848	arg1	degree					830:835	the degree	826:835	the degree of influence of terminal galactose on in vitro ADCC activity	826:896	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	12	theme	terminal	853:860	arg1	galactose					862:870	terminal galactose	853:870	terminal galactose	853:870	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	1	13	theme	cell-mediated	155:167	arg1	cytotoxicity					169:180	Antibody-dependent cell-mediated cytotoxicity	136:180	Antibody-dependent cell-mediated cytotoxicity (ADCC)	136:187	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	13	theme	cell-mediated	155:167	arg1	one					212:214	one	212:214	one	212:214	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	13	theme	cell-mediated	155:167	arg1	functions					253:261	the potentially critical effector functions	219:261	the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies	219:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	13	theme	cell-mediated	155:167	arg1	ADCC					183:186	ADCC	183:186	ADCC	183:186	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	5	14	theme	glycosylation	1036:1048	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	0	15	theme	fucose	79:84	arg1	effects					40:46	interrelated effects	27:46	interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity	27:133	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	5	16	attach	linked	972:977	arg2	absence					925:931	absence	925:931	absence	925:931	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	16	attach	linked	972:977	arg2	presence					913:920	presence	913:920	presence	913:920	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	16	attach	linked	972:977	arg1	residue					1013:1019	the first N-acetyl glucosamine residue	982:1019	the first N-acetyl glucosamine residue of an N-linked glycosylation core structure	982:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	16	attach	linked	972:977	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	0	17	theme	antibody-dependent	89:106	arg1	cytotoxicity					122:133	antibody-dependent cell-mediated cytotoxicity	89:133	antibody-dependent cell-mediated cytotoxicity	89:133	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	7	18	theme	biotherapeutic	1408:1421	arg1	antibodies					1423:1432	biotherapeutic antibodies	1408:1432	biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies	1408:1590	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	2	19	theme	ADCC	538:541	arg1	activity					543:550	increased ADCC activity	528:550	increased ADCC activity	528:550	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	7	20	link	N-linked	1555:1562	arg1	glycosylation					1564:1576	N-linked glycosylation	1555:1576	N-linked glycosylation of antibodies	1555:1590	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	4	21	theme	therapeutic	781:791	arg1	IgG1s					793:797	therapeutic IgG1s	781:797	therapeutic IgG1s	781:797	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	2	22	theme	structures	431:440	arg1	levels					392:397	higher levels	385:397	higher levels of afucosylated N-linked glycan structures on the Fc region	385:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	2	23	theme	binding	475:481	arg1	affinity					483:490	the IgG binding affinity	467:490	the IgG binding affinity to the FcγIIIa receptor	467:514	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	0	24	from	effects	40:46	arg1	cytotoxicity					122:133	antibody-dependent cell-mediated cytotoxicity	89:133	antibody-dependent cell-mediated cytotoxicity	89:133	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	2	25	gly	afucosylated	402:413	arg1	structures					431:440	afucosylated N-linked glycan structures	402:440	afucosylated N-linked glycan structures on the Fc region	402:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	4	26	theme	terminal	741:748	arg1	galactose					750:758	terminal galactose	741:758	terminal galactose	741:758	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	2	27	theme	N-linked	415:422	arg1	structures					431:440	afucosylated N-linked glycan structures	402:440	afucosylated N-linked glycan structures on the Fc region	402:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	0	28	theme	Glycan	0:5	arg1	engineering					7:17	Glycan engineering	0:17	Glycan engineering	0:17	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	1	29	theme	immunoglobin	316:327	arg1	IgG1					333:336	IgG1	333:336	IgG1	333:336	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	29	theme	immunoglobin	316:327	arg1	G1					329:330	therapeutic immunoglobin G1	304:330	some therapeutic immunoglobin G1 (IgG1) antibodies	299:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	7	30	theme	development	1381:1391	arg1	activities					1393:1402	development activities	1381:1402	development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies	1381:1590	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	5	31	theme	fucose	945:950	arg1	presence					913:920	presence	913:920	presence	913:920	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	31	theme	fucose	945:950	arg1	absence					925:931	absence	925:931	absence	925:931	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	32	theme	ADCC	884:887	arg1	activity					889:896	in vitro ADCC activity	875:896	in vitro ADCC activity	875:896	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	2	33	theme	FcγIIIa	499:505	arg1	receptor					507:514	the FcγIIIa receptor	495:514	the FcγIIIa receptor	495:514	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	6	34	contain	had	1204:1206	arg1	galactose					1089:1097	terminal galactose	1080:1097	terminal galactose on afucosylated IgG1 mAbs	1080:1123	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	34	contain	had	1204:1206	arg2	influence					1216:1224	minimal influence	1208:1224	minimal influence on ADCC activity	1208:1241	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	5	35	dep	in	875:876	arg1	vitro					878:882	vitro	878:882	vitro	878:882	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	36	theme	glucosamine	1001:1011	arg1	residue					1013:1019	the first N-acetyl glucosamine residue	982:1019	the first N-acetyl glucosamine residue of an N-linked glycosylation core structure	982:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	36	theme	glucosamine	1001:1011	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	0	37	theme	terminal	51:58	arg1	galactose					60:68	terminal galactose and core fucose	51:84	galactose	60:68	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	2	38	from	structures	431:440	arg1	region					452:457	the Fc region	445:457	the Fc region	445:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	1	39	theme	functions	253:261	arg1	one					212:214	one	212:214	one	212:214	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	39	theme	functions	253:261	arg1	cytotoxicity					169:180	Antibody-dependent cell-mediated cytotoxicity	136:180	Antibody-dependent cell-mediated cytotoxicity (ADCC)	136:187	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	39	theme	functions	253:261	arg1	functions					253:261	the potentially critical effector functions	219:261	the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies	219:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	6	40	theme	IgG1	1115:1118	arg1	mAbs					1120:1123	afucosylated IgG1 mAbs	1102:1123	afucosylated IgG1 mAbs	1102:1123	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	5	41	theme	first	986:990	arg1	residue					1013:1019	the first N-acetyl glucosamine residue	982:1019	the first N-acetyl glucosamine residue of an N-linked glycosylation core structure	982:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	41	theme	first	986:990	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	2	42	from	region	452:457	arg1	levels					392:397	higher levels	385:397	higher levels of afucosylated N-linked glycan structures on the Fc region	385:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	2	43	theme	higher	385:390	arg1	levels					392:397	higher levels	385:397	higher levels of afucosylated N-linked glycan structures on the Fc region	385:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	6	44	from	influence	1216:1224	arg1	activity					1234:1241	ADCC activity	1229:1241	ADCC activity	1229:1241	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	45	theme	terminal	1080:1087	arg1	galactose					1089:1097	terminal galactose	1080:1097	terminal galactose on afucosylated IgG1 mAbs	1080:1123	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	46	theme	%	1178:1178	arg1	%					1183:1183	ADCC%/Gal%	1174:1183	ADCC%/Gal%	1174:1183	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	46	theme	%	1178:1178	arg1	coefficients					1160:1171	impact coefficients	1153:1171	impact coefficients (ADCC%/Gal%) more than 20	1153:1197	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	47	theme	ADCC	1229:1232	arg1	activity					1234:1241	ADCC activity	1229:1241	ADCC activity	1229:1241	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	5	48	theme	galactose	862:870	arg1	influence					840:848	influence	840:848	influence of terminal galactose on in vitro ADCC activity	840:896	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	49	theme	in	875:876	arg1	activity					889:896	in vitro ADCC activity	875:896	in vitro ADCC activity	875:896	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	6	50	theme	impact	1153:1158	arg1	%					1183:1183	ADCC%/Gal%	1174:1183	ADCC%/Gal%	1174:1183	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	50	theme	impact	1153:1158	arg1	coefficients					1160:1171	impact coefficients	1153:1171	impact coefficients (ADCC%/Gal%) more than 20	1153:1197	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	51	theme	0.1-0.2	1309:1315	arg1	range					1300:1304	the range	1296:1304	the range of 0.1-0.2	1296:1315	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	3	52	theme	ADCC	618:621	arg1	activity					623:630	its ADCC activity	614:630	its ADCC activity	614:630	However, whether terminal galactosylation of an IgG1 impacts its ADCC activity is less understood.
32627435	1	53	theme	critical	235:242	arg1	functions					253:261	the potentially critical effector functions	219:261	the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies	219:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	7	54	theme	N-linked	1555:1562	arg1	glycosylation					1564:1576	N-linked glycosylation	1555:1576	N-linked glycosylation of antibodies	1555:1590	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	1	55	theme	Antibody-dependent	136:153	arg1	cytotoxicity					169:180	Antibody-dependent cell-mediated cytotoxicity	136:180	Antibody-dependent cell-mediated cytotoxicity (ADCC)	136:187	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	55	theme	Antibody-dependent	136:153	arg1	one					212:214	one	212:214	one	212:214	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	55	theme	Antibody-dependent	136:153	arg1	functions					253:261	the potentially critical effector functions	219:261	the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies	219:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	1	55	theme	Antibody-dependent	136:153	arg1	ADCC					183:186	ADCC	183:186	ADCC	183:186	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	7	56	gly	glycosylation	1564:1576	arg1	antibodies					1581:1590	antibodies	1581:1590	antibodies	1581:1590	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	6	57	theme	impact	1274:1279	arg1	coefficient					1281:1291	impact coefficient	1274:1291	impact coefficient in the range of 0.1-0.2	1274:1315	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	5	58	theme	N-linked	1027:1034	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	59	from	influence	840:848	arg1	activity					889:896	in vitro ADCC activity	875:896	in vitro ADCC activity	875:896	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	7	60	theme	antibodies	1581:1590	arg1	glycosylation					1564:1576	N-linked glycosylation	1555:1576	N-linked glycosylation of antibodies	1555:1590	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	7	61	used	used	1347:1350	arg2	Knowledge					1318:1326	Knowledge	1318:1326	Knowledge gained here	1318:1338	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	0	62	theme	core	74:77	arg1	fucose					79:84	terminal galactose and core fucose	51:84	fucose	79:84	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	5	63	theme	core	1050:1053	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	4	64	used	used	661:664	arg2	we					658:659	we	658:659	we	658:659	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	6	65	gly	fucosylated	1246:1256	arg1	structures					1258:1267	fucosylated structures	1246:1267	fucosylated structures with impact coefficient in the range of 0.1-0.2	1246:1315	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	5	66	link	N-linked	1027:1034	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	4	67	theme	glycan	685:690	arg1	enrichment					692:701	glycan enrichment	685:701	glycan enrichment	685:701	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	6	68	gly	afucosylated	1102:1113	arg1	mAbs					1120:1123	afucosylated IgG1 mAbs	1102:1123	afucosylated IgG1 mAbs	1102:1123	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	0	69	theme	cell-mediated	108:120	arg1	cytotoxicity					122:133	antibody-dependent cell-mediated cytotoxicity	89:133	antibody-dependent cell-mediated cytotoxicity	89:133	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	7	70	theme	immune	1531:1536	arg1	response					1538:1545	the immune response	1527:1545	the immune response	1527:1545	Knowledge gained here can be used to guide product and process development activities for biotherapeutic antibodies that require effector function for efficacy, and also highlight the complexity in modulating the immune response through N-linked glycosylation of antibodies.
32627435	4	71	theme	ADCC	763:766	arg1	activity					768:775	ADCC activity	763:775	ADCC activity for therapeutic IgG1s	763:797	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	5	72	from	degree	830:835	arg1	activity					889:896	in vitro ADCC activity	875:896	in vitro ADCC activity	875:896	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	73	from	activity	889:896	arg1	degree					830:835	the degree	826:835	the degree of influence of terminal galactose on in vitro ADCC activity	826:896	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	2	74	theme	increased	528:536	arg1	activity					543:550	increased ADCC activity	528:550	increased ADCC activity	528:550	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	5	75	dep	presence	913:920	arg1	the					909:911	the	909:911	the	909:911	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	2	76	theme	glycan	424:429	arg1	structures					431:440	afucosylated N-linked glycan structures	402:440	afucosylated N-linked glycan structures on the Fc region	402:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	2	77	theme	IgG	471:473	arg1	affinity					483:490	the IgG binding affinity	467:490	the IgG binding affinity to the FcγIIIa receptor	467:514	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	2	78	theme	afucosylated	402:413	arg1	structures					431:440	afucosylated N-linked glycan structures	402:440	afucosylated N-linked glycan structures on the Fc region	402:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	0	79	theme	interrelated	27:38	arg1	effects					40:46	interrelated effects	27:46	interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity	27:133	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	1	80	theme	G1	329:330	arg1	antibodies					339:348	some therapeutic immunoglobin G1 (IgG1) antibodies	299:348	some therapeutic immunoglobin G1 (IgG1) antibodies	299:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	5	81	theme	core	940:943	arg1	fucose					945:950	the core fucose	936:950	the core fucose	936:950	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	2	82	link	N-linked	415:422	arg1	structures					431:440	afucosylated N-linked glycan structures	402:440	afucosylated N-linked glycan structures on the Fc region	402:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	4	83	theme	galactose	750:758	arg1	impact					731:736	the impact	727:736	the impact of terminal galactose on ADCC activity for therapeutic IgG1s	727:797	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	2	84	theme	Fc	449:450	arg1	region					452:457	the Fc region	445:457	the Fc region	445:457	It has been well established that higher levels of afucosylated N-linked glycan structures on the Fc region enhance the IgG binding affinity to the FcγIIIa receptor and lead to increased ADCC activity.
32627435	5	85	theme	N-acetyl	992:999	arg1	residue					1013:1019	the first N-acetyl glucosamine residue	982:1019	the first N-acetyl glucosamine residue of an N-linked glycosylation core structure	982:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	5	85	theme	N-acetyl	992:999	arg1	structure					1055:1063	an N-linked glycosylation core structure	1024:1063	an N-linked glycosylation core structure	1024:1063	Our results indicate that the degree of influence of terminal galactose on in vitro ADCC activity depends on the presence or absence of the core fucose, which is typically linked to the first N-acetyl glucosamine residue of an N-linked glycosylation core structure.
32627435	0	86	theme	galactose	60:68	arg1	effects					40:46	interrelated effects	27:46	interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity	27:133	Glycan engineering reveals interrelated effects of terminal galactose and core fucose on antibody-dependent cell-mediated cytotoxicity.
32627435	1	87	theme	antibodies	339:348	arg1	efficacy					287:294	the clinical efficacy	274:294	the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies	274:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	6	88	theme	ADCC	1134:1137	arg1	activity					1139:1146	ADCC activity	1134:1146	ADCC activity	1134:1146	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	4	89	from	impact	731:736	arg1	activity					768:775	ADCC activity	763:775	ADCC activity for therapeutic IgG1s	763:797	Here, we used a new strategy for glycan enrichment and remodeling to study the impact of terminal galactose on ADCC activity for therapeutic IgG1s.
32627435	6	90	from	coefficient	1281:1291	arg1	range					1300:1304	the range	1296:1304	the range of 0.1-0.2	1296:1315	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	91	from	galactose	1089:1097	arg1	mAbs					1120:1123	afucosylated IgG1 mAbs	1102:1123	afucosylated IgG1 mAbs	1102:1123	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	6	92	with	structures	1258:1267	arg1	coefficient					1281:1291	impact coefficient	1274:1291	impact coefficient in the range of 0.1-0.2	1274:1315	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	1	93	theme	effector	244:251	arg1	functions					253:261	the potentially critical effector functions	219:261	the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies	219:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
32627435	6	94	theme	afucosylated	1102:1113	arg1	mAbs					1120:1123	afucosylated IgG1 mAbs	1102:1123	afucosylated IgG1 mAbs	1102:1123	Specifically, terminal galactose on afucosylated IgG1 mAbs enhanced ADCC activity with impact coefficients (ADCC%/Gal%) more than 20, but had minimal influence on ADCC activity on fucosylated structures with impact coefficient in the range of 0.1-0.2.
32627435	1	95	theme	clinical	278:285	arg1	efficacy					287:294	the clinical efficacy	274:294	the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies	274:348	Antibody-dependent cell-mediated cytotoxicity (ADCC) has been identified as one of the potentially critical effector functions underlying the clinical efficacy of some therapeutic immunoglobin G1 (IgG1) antibodies.
33983715	8	0	theme	autophagy	1557:1565	arg1	observation					1523:1533	the observation	1519:1533	the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics	1519:1599	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	2	1	theme	stress	321:326	arg1	degree					311:316	the degree	307:316	the degree of stress	307:326	Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress.
33983715	7	2	theme	ER	1389:1390	arg1	stress					1392:1397	ER stress	1389:1397	ER stress	1389:1397	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	8	3	theme	ER-phagy	1570:1577	arg1	observation					1523:1533	the observation	1519:1533	the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics	1519:1599	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	7	4	theme	ER	1337:1338	arg1	stress					1340:1345	ER stress	1337:1345	ER stress	1337:1345	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	5	5	theme	changes	835:841	arg1	determination					814:826	quantitative determination	801:826	quantitative determination of the changes in the structures of N-glycans	801:872	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	9	6	theme	N-glycoforms	1627:1638	arg1	analysis					1615:1622	Quantitative analysis	1602:1622	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs	1602:1669	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	7	7	theme	N-glycans	1312:1320	arg1	ratio					1292:1296	the ratio	1288:1296	the ratio of sialylated N-glycans in response to ER stress	1288:1345	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	5	8	theme	line	788:791	arg1	analysis					762:769	Glycoblotting-assisted mass spectrometric analysis	720:769	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line	720:791	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	7	9	gly	sialylated	1301:1310	arg1	N-glycans					1312:1320	sialylated N-glycans	1301:1320	sialylated N-glycans	1301:1320	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	5	10	theme	quantitative	801:812	arg1	determination					814:826	quantitative determination	801:826	quantitative determination of the changes in the structures of N-glycans	801:872	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	2	11	dep	difficult	270:278	arg1	evaluate					298:305	evaluate	298:305	to quantitatively evaluate the degree of stress	280:326	Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress.
33983715	2	11	dep	difficult	270:278	arg1	identify					335:342	identify	335:342	to identify the cause of the stress	332:366	Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress.
33983715	1	12	theme	Endoplasmic	121:131	arg1	reticulum					133:141	Endoplasmic reticulum	121:141	Endoplasmic reticulum (ER) stress	121:153	Endoplasmic reticulum (ER) stress has been reported in a variety of diseases.
33983715	1	12	theme	Endoplasmic	121:131	arg1	ER					144:145	ER	144:145	ER	144:145	Endoplasmic reticulum (ER) stress has been reported in a variety of diseases.
33983715	5	13	theme	free	887:890	arg1	fOSs					910:913	fOSs	910:913	fOSs	910:913	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	5	13	theme	free	887:890	arg1	oligosaccharides					892:907	free oligosaccharides	887:907	free oligosaccharides (fOSs)	887:914	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	6	14	theme	integrated	983:992	arg1	analysis					994:1001	The integrated analysis	979:1001	The integrated analysis of neutral and sialylated N-glycans and fOSs	979:1046	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	9	15	theme	dynamic	1684:1690	arg1	indicators					1692:1701	the dynamic indicators	1680:1701	the dynamic indicators reflecting the ER status	1680:1726	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	7	16	theme	type	1239:1242	arg1	N-glycans					1244:1252	high-mannose type N-glycans	1226:1252	high-mannose type N-glycans	1226:1252	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	17	theme	total	1176:1180	arg1	glycans					1192:1198	glycans	1192:1198	glycans	1192:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	17	theme	total	1176:1180	arg1	amount					1182:1187	the total amount	1172:1187	the total amount of glycans	1172:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	5	18	from	determination	814:826	arg1	structures					850:859	the structures	846:859	the structures of N-glycans	846:872	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	5	19	from	structures	850:859	arg1	determination					814:826	quantitative determination	801:826	quantitative determination of the changes in the structures of N-glycans	801:872	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	9	20	theme	ER	1718:1719	arg1	status					1721:1726	the ER status	1714:1726	the ER status	1714:1726	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	8	21	theme	drastic	1414:1420	arg1	clearance					1422:1430	drastic clearance	1414:1430	drastic clearance of accumulated N-glycans	1414:1455	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	4	22	theme	stress	712:717	arg1	descriptor					695:704	a quantitative descriptor	680:704	a quantitative descriptor of ER stress	680:717	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	3	23	theme	primary	383:389	arg1	site					391:394	the primary site	379:394	the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated	379:498	The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated.
33983715	3	23	theme	primary	383:389	arg1	ER					373:374	The ER	369:374	The ER	369:374	The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated.
33983715	0	24	theme	ER	110:111	arg1	Stress					113:118	ER Stress	110:118	ER Stress	110:118	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	5	25	theme	tunicamycin-	931:942	arg1	stress					971:976	tunicamycin- or thapsigargin-induced ER stress	931:976	tunicamycin- or thapsigargin-induced ER stress	931:976	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	7	26	from	changes	1277:1283	arg1	glycans					1192:1198	glycans	1192:1198	glycans	1192:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	26	from	changes	1277:1283	arg1	ratio					1292:1296	the ratio	1288:1296	the ratio of sialylated N-glycans in response to ER stress	1288:1345	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	26	from	changes	1277:1283	arg1	amount					1182:1187	the total amount	1172:1187	the total amount of glycans	1172:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	26	from	changes	1277:1283	arg1	ratio					1217:1221	the ratio	1213:1221	the ratio of high-mannose type N-glycans	1213:1252	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	26	from	changes	1277:1283	arg1	fOSs					1267:1270	fOSs	1267:1270	fOSs	1267:1270	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	6	27	theme	fOSs	1043:1046	arg1	analysis					994:1001	The integrated analysis	979:1001	The integrated analysis of neutral and sialylated N-glycans and fOSs	979:1046	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	9	28	theme	promising	1736:1744	arg1	strategies					1746:1755	the promising strategies	1732:1755	the promising strategies for quantitative evaluation of ER stress	1732:1796	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	8	29	theme	N-glycans	1447:1455	arg1	clearance					1422:1430	drastic clearance	1414:1430	drastic clearance of accumulated N-glycans	1414:1455	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	0	30	theme	Integrated	0:9	arg1	Analysis					22:29	Integrated Structural Analysis	0:29	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides	0:68	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	6	31	theme	N-glycans	1029:1037	arg1	analysis					994:1001	The integrated analysis	979:1001	The integrated analysis of neutral and sialylated N-glycans and fOSs	979:1046	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	4	32	theme	quantitative	682:693	arg1	descriptor					695:704	a quantitative descriptor	680:704	a quantitative descriptor of ER stress	680:717	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	5	33	theme	HeLa	778:781	arg1	line					788:791	the HeLa cell line	774:791	the HeLa cell line	774:791	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	4	34	link	asparagine-linked	574:590	arg1	N-glycans					601:609	N-glycans	601:609	N-glycans	601:609	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	4	34	link	asparagine-linked	574:590	arg1	glycans					592:598	asparagine-linked glycans	574:598	asparagine-linked glycans (N-glycans)	574:610	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	7	35	theme	N-glycans	1244:1252	arg1	ratio					1217:1221	the ratio	1213:1221	the ratio of high-mannose type N-glycans	1213:1252	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	8	36	theme	thapsigargin-treated	1473:1492	arg1	cells					1494:1498	thapsigargin-treated cells	1473:1498	thapsigargin-treated cells	1473:1498	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	0	37	theme	N-Glycans	34:42	arg1	Oligosaccharides					53:68	N-Glycans and Free Oligosaccharides	34:68	N-Glycans and Free Oligosaccharides	34:68	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	5	38	theme	Glycoblotting-assisted	720:741	arg1	analysis					762:769	Glycoblotting-assisted mass spectrometric analysis	720:769	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line	720:791	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	8	39	located	observed	1461:1468	arg1	cells					1494:1498	thapsigargin-treated cells	1473:1498	thapsigargin-treated cells	1473:1498	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	8	39	located	observed	1461:1468	arg2	clearance					1422:1430	drastic clearance	1414:1430	drastic clearance of accumulated N-glycans	1414:1455	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	7	40	theme	high-mannose	1226:1237	arg1	N-glycans					1244:1252	high-mannose type N-glycans	1226:1252	high-mannose type N-glycans	1226:1252	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	9	41	theme	ER	1788:1789	arg1	stress					1791:1796	ER stress	1788:1796	ER stress	1788:1796	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	3	42	theme	proteins	438:445	arg1	folding					400:406	folding	400:406	folding of secretory or transmembrane proteins	400:445	The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated.
33983715	5	43	theme	spectrometric	748:760	arg1	analysis					762:769	Glycoblotting-assisted mass spectrometric analysis	720:769	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line	720:791	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	5	44	theme	thapsigargin-induced	947:966	arg1	stress					971:976	tunicamycin- or thapsigargin-induced ER stress	931:976	tunicamycin- or thapsigargin-induced ER stress	931:976	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	4	45	theme	biosynthetic	550:561	arg1	pathway					563:569	the biosynthetic pathway	546:569	the biosynthetic pathway of asparagine-linked glycans (N-glycans)	546:610	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	5	46	theme	mass	743:746	arg1	analysis					762:769	Glycoblotting-assisted mass spectrometric analysis	720:769	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line	720:791	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	7	47	theme	stress	1392:1397	arg1	descriptors					1374:1384	potential descriptors	1364:1384	potential descriptors of ER stress	1364:1397	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	8	48	theme	stress-mediated	1541:1555	arg1	autophagy					1557:1565	ER stress-mediated autophagy	1538:1565	ER stress-mediated autophagy	1538:1565	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	7	49	theme	potential	1364:1372	arg1	descriptors					1374:1384	potential descriptors	1364:1384	potential descriptors of ER stress	1364:1397	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	0	50	theme	Free	48:51	arg1	Oligosaccharides					53:68	N-Glycans and Free Oligosaccharides	34:68	N-Glycans and Free Oligosaccharides	34:68	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	9	51	theme	Quantitative	1602:1613	arg1	analysis					1615:1622	Quantitative analysis	1602:1622	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs	1602:1669	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	7	52	from	increase	1201:1208	arg1	glycans					1192:1198	glycans	1192:1198	glycans	1192:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	52	from	increase	1201:1208	arg1	ratio					1292:1296	the ratio	1288:1296	the ratio of sialylated N-glycans in response to ER stress	1288:1345	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	52	from	increase	1201:1208	arg1	amount					1182:1187	the total amount	1172:1187	the total amount of glycans	1172:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	52	from	increase	1201:1208	arg1	ratio					1217:1221	the ratio	1213:1221	the ratio of high-mannose type N-glycans	1213:1252	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	52	from	increase	1201:1208	arg1	fOSs					1267:1270	fOSs	1267:1270	fOSs	1267:1270	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	5	53	theme	cell	783:786	arg1	line					788:791	the HeLa cell line	774:791	the HeLa cell line	774:791	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	6	54	theme	stress	1098:1103	arg1	cause					1086:1090	the cause	1082:1090	the cause of ER stress, which cannot be readily done by protein markers alone	1082:1158	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	4	55	theme	glycans	592:598	arg1	pathway					563:569	the biosynthetic pathway	546:569	the biosynthetic pathway of asparagine-linked glycans (N-glycans)	546:610	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	8	56	from	observation	1523:1533	arg1	terms					1582:1586	terms	1582:1586	terms of glycomics	1582:1599	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	1	57	theme	diseases	189:196	arg1	diseases					189:196	diseases	189:196	diseases	189:196	Endoplasmic reticulum (ER) stress has been reported in a variety of diseases.
33983715	1	57	theme	diseases	189:196	arg1	variety					178:184	a variety	176:184	a variety of diseases	176:196	Endoplasmic reticulum (ER) stress has been reported in a variety of diseases.
33983715	7	58	theme	sialylated	1301:1310	arg1	N-glycans					1312:1320	sialylated N-glycans	1301:1320	sialylated N-glycans	1301:1320	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	2	59	theme	ER	208:209	arg1	stress					211:216	ER stress	208:216	ER stress	208:216	Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress.
33983715	5	60	theme	N-glycans	864:872	arg1	structures					850:859	the structures	846:859	the structures of N-glycans	846:872	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	7	61	from	Changes	1161:1167	arg1	glycans					1192:1198	glycans	1192:1198	glycans	1192:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	61	from	Changes	1161:1167	arg1	ratio					1292:1296	the ratio	1288:1296	the ratio of sialylated N-glycans in response to ER stress	1288:1345	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	61	from	Changes	1161:1167	arg1	amount					1182:1187	the total amount	1172:1187	the total amount of glycans	1172:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	61	from	Changes	1161:1167	arg1	ratio					1217:1221	the ratio	1213:1221	the ratio of high-mannose type N-glycans	1213:1252	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	61	from	Changes	1161:1167	arg1	fOSs					1267:1270	fOSs	1267:1270	fOSs	1267:1270	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	2	62	theme	specific	240:247	arg1	markers					249:255	specific markers	240:255	specific markers	240:255	Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress.
33983715	1	63	theme	reticulum	133:141	arg1	stress					148:153	Endoplasmic reticulum (ER) stress	121:153	Endoplasmic reticulum (ER) stress	121:153	Endoplasmic reticulum (ER) stress has been reported in a variety of diseases.
33983715	4	64	theme	ER	664:665	arg1	state					651:655	the state	647:655	the state of the ER	647:665	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	5	65	from	changes	835:841	arg1	structures					850:859	the structures	846:859	the structures of N-glycans	846:872	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	6	66	theme	protein	1138:1144	arg1	markers					1146:1152	protein markers	1138:1152	protein markers alone	1138:1158	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	0	67	theme	Quantitative	83:94	arg1	Evaluation					96:105	a Quantitative Evaluation	81:105	a Quantitative Evaluation of ER Stress	81:118	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	8	68	theme	accumulated	1435:1445	arg1	N-glycans					1447:1455	accumulated N-glycans	1435:1455	accumulated N-glycans	1435:1455	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	0	69	theme	Stress	113:118	arg1	Evaluation					96:105	a Quantitative Evaluation	81:105	a Quantitative Evaluation of ER Stress	81:118	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	4	70	theme	ER	709:710	arg1	stress					712:717	ER stress	709:717	ER stress	709:717	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	0	71	theme	Structural	11:20	arg1	Analysis					22:29	Integrated Structural Analysis	0:29	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides	0:68	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	7	72	from	ratio	1292:1296	arg1	response					1325:1332	response	1325:1332	response to ER stress	1325:1345	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	6	73	theme	sialylated	1018:1027	arg1	N-glycans					1029:1037	neutral and sialylated N-glycans	1006:1037	neutral and sialylated N-glycans	1006:1037	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	9	74	theme	quantitative	1761:1772	arg1	evaluation					1774:1783	quantitative evaluation	1761:1783	quantitative evaluation of ER stress	1761:1796	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	6	75	gly	sialylated	1018:1027	arg1	N-glycans					1029:1037	neutral and sialylated N-glycans	1006:1037	neutral and sialylated N-glycans	1006:1037	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	3	76	theme	secretory	411:419	arg1	proteins					438:445	secretory or transmembrane proteins	411:445	secretory or transmembrane proteins	411:445	The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated.
33983715	6	77	theme	neutral	1006:1012	arg1	N-glycans					1029:1037	neutral and sialylated N-glycans	1006:1037	neutral and sialylated N-glycans	1006:1037	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	4	78	theme	asparagine-linked	574:590	arg1	N-glycans					601:609	N-glycans	601:609	N-glycans	601:609	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	4	78	theme	asparagine-linked	574:590	arg1	glycans					592:598	asparagine-linked glycans	574:598	asparagine-linked glycans (N-glycans)	574:610	This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (N-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress.
33983715	2	79	theme	stress	361:366	arg1	cause					348:352	the cause	344:352	the cause of the stress	344:366	Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress.
33983715	0	80	theme	Oligosaccharides	53:68	arg1	Analysis					22:29	Integrated Structural Analysis	0:29	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides	0:68	Integrated Structural Analysis of N-Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.
33983715	6	81	theme	ER	1095:1096	arg1	stress					1098:1103	ER stress	1095:1103	ER stress	1095:1103	The integrated analysis of neutral and sialylated N-glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone.
33983715	9	82	theme	stress	1791:1796	arg1	evaluation					1774:1783	quantitative evaluation	1761:1783	quantitative evaluation of ER stress	1761:1796	Quantitative analysis of N-glycoforms composed of N-glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
33983715	3	83	theme	transmembrane	424:436	arg1	proteins					438:445	secretory or transmembrane proteins	411:445	secretory or transmembrane proteins	411:445	The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated.
33983715	8	84	theme	glycomics	1591:1599	arg1	terms					1582:1586	terms	1582:1586	terms of glycomics	1582:1599	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
33983715	5	85	theme	ER	968:969	arg1	stress					971:976	tunicamycin- or thapsigargin-induced ER stress	931:976	tunicamycin- or thapsigargin-induced ER stress	931:976	Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of N-glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress.
33983715	7	86	from	increase	1255:1262	arg1	glycans					1192:1198	glycans	1192:1198	glycans	1192:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	86	from	increase	1255:1262	arg1	ratio					1292:1296	the ratio	1288:1296	the ratio of sialylated N-glycans in response to ER stress	1288:1345	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	86	from	increase	1255:1262	arg1	amount					1182:1187	the total amount	1172:1187	the total amount of glycans	1172:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	86	from	increase	1255:1262	arg1	ratio					1217:1221	the ratio	1213:1221	the ratio of high-mannose type N-glycans	1213:1252	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	86	from	increase	1255:1262	arg1	fOSs					1267:1270	fOSs	1267:1270	fOSs	1267:1270	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	87	theme	glycans	1192:1198	arg1	glycans					1192:1198	glycans	1192:1198	glycans	1192:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	7	87	theme	glycans	1192:1198	arg1	amount					1182:1187	the total amount	1172:1187	the total amount of glycans	1172:1198	Changes in the total amount of glycans, increase in the ratio of high-mannose type N-glycans, increase in fOSs, and changes in the ratio of sialylated N-glycans in response to ER stress were shown to be potential descriptors of ER stress.
33983715	8	88	theme	ER	1538:1539	arg1	autophagy					1557:1565	ER stress-mediated autophagy	1538:1565	ER stress-mediated autophagy	1538:1565	Additionally, drastic clearance of accumulated N-glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics.
32681150	9	0	theme	time	1338:1341	arg1	spent					1343:1347	the time spent	1334:1347	the time spent on instrumental and data analyses	1334:1381	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	9	1	dep	5	1404:1404	arg1	to					1401:1402	to	1401:1402	to	1401:1402	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	1	2	theme	outermost	166:174	arg1	layer					176:180	the outermost layer	162:180	the outermost layer of cells	162:189	The glycocalyx comprises glycosylated proteins and lipids and fcorms the outermost layer of cells.
32681150	12	3	theme	broad	1737:1741	arg1	therapeutics					1841:1852	therapeutics	1841:1852	therapeutics	1841:1852	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	3	theme	broad	1737:1741	arg1	range					1743:1747	a broad range	1735:1747	a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics	1735:1852	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	3	theme	broad	1737:1741	arg1	discovery					1827:1835	glycan-based biomarker discovery	1804:1835	glycan-based biomarker discovery	1804:1835	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	0	4	theme	tissues	84:90	arg1	glycocalyxes					58:69	the glycocalyxes	54:69	the glycocalyxes of cells and tissues	54:90	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.
32681150	6	5	theme	LC-tandem	886:894	arg1	analysis					910:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	Sample preparation, quantitative LC-tandem MS (LC-MS/MS) analysis, and data processing methods are provided.
32681150	12	6	theme	fundamental	1752:1762	arg1	therapeutics					1841:1852	therapeutics	1841:1852	therapeutics	1841:1852	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	6	theme	fundamental	1752:1762	arg1	discovery					1827:1835	glycan-based biomarker discovery	1804:1835	glycan-based biomarker discovery	1804:1835	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	6	theme	fundamental	1752:1762	arg1	studies					1785:1791	fundamental and applied clinical studies	1752:1791	fundamental and applied clinical studies	1752:1791	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	4	7	theme	glycoproteins	626:638	arg1	O-glycans					613:621	the glycocalyx N-glycans and O-glycans	584:621	O-glycans	613:621	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	4	7	theme	glycoproteins	626:638	arg1	N-glycans					599:607	the glycocalyx N-glycans and O-glycans	584:621	N-glycans	599:607	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	8	8	theme	glycoproteomic	1212:1225	arg1	analysis					1227:1234	glycoproteomic analysis	1212:1234	glycoproteomic analysis	1212:1234	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	12	9	dep	clinical	1776:1783	arg1	applied					1768:1774	applied	1768:1774	applied	1768:1774	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	7	10	theme	site-specific	1026:1038	arg1	glycosylation					1040:1052	the site-specific glycosylation	1022:1052	the site-specific glycosylation of membrane proteins	1022:1073	In addition, we discuss glycoproteomic analysis that yields the site-specific glycosylation of membrane proteins.
32681150	6	11	theme	quantitative	873:884	arg1	analysis					910:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	Sample preparation, quantitative LC-tandem MS (LC-MS/MS) analysis, and data processing methods are provided.
32681150	2	12	theme	cell	309:312	arg1	signaling					314:322	cell signaling	309:322	cell signaling	309:322	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	9	13	dep	instrumental	1352:1363	arg1	analyses					1374:1381	analyses	1374:1381	analyses	1374:1381	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	8	14	theme	sample	1100:1105	arg1	sample					1100:1105	sample	1100:1105	sample	1100:1105	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	8	14	theme	sample	1100:1105	arg1	amount					1090:1095	the amount	1086:1095	the amount of sample needed	1086:1112	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	8	15	theme	same	1180:1183	arg1	fraction					1194:1201	the same enriched fraction	1176:1201	the same enriched fraction	1176:1201	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	1	16	gly	glycosylated	118:129	arg1	proteins					131:138	glycosylated proteins	118:138	glycosylated proteins	118:138	The glycocalyx comprises glycosylated proteins and lipids and fcorms the outermost layer of cells.
32681150	8	17	theme	N-glycan	1115:1122	arg1	analyses					1150:1157	N-glycan, O-glycan, and glycolipid analyses	1115:1157	N-glycan, O-glycan, and glycolipid analyses	1115:1157	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	8	18	dep	performed	1163:1171	arg1	whereas					1204:1210	whereas	1204:1210	whereas	1204:1210	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	4	19	theme	enriched	699:706	arg1	fraction					717:724	the same enriched membrane fraction	690:724	the same enriched membrane fraction	690:724	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	4	20	from	glycoproteins	626:638	arg1	parallel					674:681	parallel	674:681	parallel	674:681	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	11	21	theme	specific	1550:1557	arg1	glycoforms					1559:1568	specific glycoforms	1550:1568	specific glycoforms	1550:1568	Systematic changes in the glycocalyx associated with specific glycoforms and glycoconjugates can be monitored with quantitation using this protocol.
32681150	4	22	gly	glycoproteins	626:638	arg1	glycoproteins					626:638	glycoproteins	626:638	glycoproteins	626:638	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	2	23	theme	self-cell	286:294	arg1	recognition					296:306	self-cell recognition	286:306	self-cell recognition	286:306	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	1	24	theme	cells	185:189	arg1	layer					176:180	the outermost layer	162:180	the outermost layer of cells	162:189	The glycocalyx comprises glycosylated proteins and lipids and fcorms the outermost layer of cells.
32681150	0	25	theme	structural	14:23	arg1	characterization					34:49	Comprehensive structural glycomic characterization	0:49	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.	0:91	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.
32681150	6	26	theme	processing	929:938	arg1	methods					940:946	data processing methods	924:946	data processing methods	924:946	Sample preparation, quantitative LC-tandem MS (LC-MS/MS) analysis, and data processing methods are provided.
32681150	8	27	theme	O-glycan	1125:1132	arg1	analyses					1150:1157	N-glycan, O-glycan, and glycolipid analyses	1115:1157	N-glycan, O-glycan, and glycolipid analyses	1115:1157	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	8	28	theme	enriched	1185:1192	arg1	fraction					1194:1201	the same enriched fraction	1176:1201	the same enriched fraction	1176:1201	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	2	29	theme	structure	334:342	arg1	maintenance					344:354	cellular structure maintenance	325:354	cellular structure maintenance	325:354	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	7	30	theme	glycoproteomic	986:999	arg1	analysis					1001:1008	glycoproteomic analysis	986:1008	glycoproteomic analysis that yields the site-specific glycosylation of membrane proteins	986:1073	In addition, we discuss glycoproteomic analysis that yields the site-specific glycosylation of membrane proteins.
32681150	0	31	theme	Comprehensive	0:12	arg1	characterization					34:49	Comprehensive structural glycomic characterization	0:49	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.	0:91	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.
32681150	10	32	theme	tissue	1481:1486	arg1	samples					1488:1494	tissue samples	1481:1494	tissue samples	1481:1494	This workflow is applicable to both cell and tissue samples.
32681150	12	33	theme	biomarker	1817:1825	arg1	discovery					1827:1835	glycan-based biomarker discovery	1804:1835	glycan-based biomarker discovery	1804:1835	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	2	34	theme	cellular	325:332	arg1	maintenance					344:354	cellular structure maintenance	325:354	cellular structure maintenance	325:354	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	12	35	theme	clinical	1776:1783	arg1	therapeutics					1841:1852	therapeutics	1841:1852	therapeutics	1841:1852	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	35	theme	clinical	1776:1783	arg1	discovery					1827:1835	glycan-based biomarker discovery	1804:1835	glycan-based biomarker discovery	1804:1835	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	35	theme	clinical	1776:1783	arg1	studies					1785:1791	fundamental and applied clinical studies	1752:1791	fundamental and applied clinical studies	1752:1791	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	4	36	theme	membrane	708:715	arg1	fraction					717:724	the same enriched membrane fraction	690:724	the same enriched membrane fraction	690:724	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	8	37	theme	separate	1254:1261	arg1	fraction					1272:1279	a separate enriched fraction	1252:1279	a separate enriched fraction	1252:1279	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	4	38	from	O-glycans	613:621	arg1	parallel					674:681	parallel	674:681	parallel	674:681	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	5	39	theme	glycans	744:750	arg1	Profiling					727:735	Profiling	727:735	Profiling of the glycans and the glycolipids	727:770	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	12	40	theme	glycan-based	1804:1815	arg1	discovery					1827:1835	glycan-based biomarker discovery	1804:1835	glycan-based biomarker discovery	1804:1835	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	11	41	theme	Systematic	1497:1506	arg1	changes					1508:1514	Systematic changes	1497:1514	Systematic changes in the glycocalyx associated with specific glycoforms and glycoconjugates	1497:1588	Systematic changes in the glycocalyx associated with specific glycoforms and glycoconjugates can be monitored with quantitation using this protocol.
32681150	3	42	theme	glycocalyx	404:413	arg1	Characterization					380:395	Characterization	380:395	Characterization of the glycocalyx	380:413	Characterization of the glycocalyx is thus essential to understanding cell physiology and elucidating its role in promoting health and disease.
32681150	12	43	theme	individual	1672:1681	arg1	glycoforms					1683:1692	individual glycoforms	1672:1692	individual glycoforms	1672:1692	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	6	44	theme	data	924:927	arg1	methods					940:946	data processing methods	924:946	data processing methods	924:946	Sample preparation, quantitative LC-tandem MS (LC-MS/MS) analysis, and data processing methods are provided.
32681150	1	45	theme	glycosylated	118:129	arg1	proteins					131:138	glycosylated proteins	118:138	glycosylated proteins	118:138	The glycocalyx comprises glycosylated proteins and lipids and fcorms the outermost layer of cells.
32681150	9	46	from	spent	1343:1347	arg1	data					1369:1372	data	1369:1372	data	1369:1372	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	9	46	from	spent	1343:1347	arg1	instrumental					1352:1363	instrumental	1352:1363	instrumental	1352:1363	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	7	47	gly	glycosylation	1040:1052	arg1	proteins					1066:1073	membrane proteins	1057:1073	membrane proteins	1057:1073	In addition, we discuss glycoproteomic analysis that yields the site-specific glycosylation of membrane proteins.
32681150	9	48	theme	preparation	1293:1303	arg1	process					1305:1311	The sample preparation process	1282:1311	The sample preparation process	1282:1311	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	4	49	from	parallel	674:681	arg1	O-glycans					613:621	the glycocalyx N-glycans and O-glycans	584:621	O-glycans	613:621	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	4	49	from	parallel	674:681	arg1	N-glycans					599:607	the glycocalyx N-glycans and O-glycans	584:621	N-glycans	599:607	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	3	50	theme	cell	450:453	arg1	physiology					455:464	cell physiology	450:464	cell physiology	450:464	Characterization of the glycocalyx is thus essential to understanding cell physiology and elucidating its role in promoting health and disease.
32681150	5	51	theme	glycolipids	760:770	arg1	Profiling					727:735	Profiling	727:735	Profiling of the glycans and the glycolipids	727:770	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	2	52	theme	intracellular	233:245	arg1	protection					368:377	immune protection	361:377	immune protection	361:377	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	52	theme	intracellular	233:245	arg1	processes					247:255	fundamental inter- and intracellular processes	210:255	fundamental inter- and intracellular processes	210:255	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	52	theme	intracellular	233:245	arg1	recognition					296:306	self-cell recognition	286:306	self-cell recognition	286:306	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	52	theme	intracellular	233:245	arg1	maintenance					344:354	cellular structure maintenance	325:354	cellular structure maintenance	325:354	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	52	theme	intracellular	233:245	arg1	non-self-cell					268:280	non-self-cell	268:280	non-self-cell	268:280	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	52	theme	intracellular	233:245	arg1	signaling					314:322	cell signaling	309:322	cell signaling	309:322	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	5	53	theme	nanoflow	791:798	arg1	nanoLC-MS					841:849	nanoLC-MS	841:849	nanoLC-MS	841:849	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	5	53	theme	nanoflow	791:798	arg1	spectrometry					827:838	nanoflow liquid chromatography-mass spectrometry	791:838	nanoflow liquid chromatography-mass spectrometry (nanoLC-MS)	791:850	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	8	54	theme	enriched	1263:1270	arg1	fraction					1272:1279	a separate enriched fraction	1252:1279	a separate enriched fraction	1252:1279	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	4	55	from	glycolipids	659:669	arg1	parallel					674:681	parallel	674:681	parallel	674:681	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	2	56	theme	immune	361:366	arg1	protection					368:377	immune protection	361:377	immune protection	361:377	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	0	57	theme	glycocalyxes	58:69	arg1	characterization					34:49	Comprehensive structural glycomic characterization	0:49	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.	0:91	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.
32681150	4	58	theme	glycocalyx	588:597	arg1	N-glycans					599:607	the glycocalyx N-glycans and O-glycans	584:621	N-glycans	599:607	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	2	59	theme	fundamental	210:220	arg1	protection					368:377	immune protection	361:377	immune protection	361:377	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	59	theme	fundamental	210:220	arg1	processes					247:255	fundamental inter- and intracellular processes	210:255	fundamental inter- and intracellular processes	210:255	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	59	theme	fundamental	210:220	arg1	recognition					296:306	self-cell recognition	286:306	self-cell recognition	286:306	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	59	theme	fundamental	210:220	arg1	maintenance					344:354	cellular structure maintenance	325:354	cellular structure maintenance	325:354	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	59	theme	fundamental	210:220	arg1	non-self-cell					268:280	non-self-cell	268:280	non-self-cell	268:280	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	59	theme	fundamental	210:220	arg1	signaling					314:322	cell signaling	309:322	cell signaling	309:322	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	60	theme	inter-	222:227	arg1	protection					368:377	immune protection	361:377	immune protection	361:377	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	60	theme	inter-	222:227	arg1	processes					247:255	fundamental inter- and intracellular processes	210:255	fundamental inter- and intracellular processes	210:255	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	60	theme	inter-	222:227	arg1	recognition					296:306	self-cell recognition	286:306	self-cell recognition	286:306	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	60	theme	inter-	222:227	arg1	maintenance					344:354	cellular structure maintenance	325:354	cellular structure maintenance	325:354	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	60	theme	inter-	222:227	arg1	non-self-cell					268:280	non-self-cell	268:280	non-self-cell	268:280	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	2	60	theme	inter-	222:227	arg1	signaling					314:322	cell signaling	309:322	cell signaling	309:322	It is involved in fundamental inter- and intracellular processes, including non-self-cell and self-cell recognition, cell signaling, cellular structure maintenance, and immune protection.
32681150	11	61	from	changes	1508:1514	arg1	glycocalyx					1523:1532	the glycocalyx	1519:1532	the glycocalyx associated with specific glycoforms and glycoconjugates	1519:1588	Systematic changes in the glycocalyx associated with specific glycoforms and glycoconjugates can be monitored with quantitation using this protocol.
32681150	6	62	theme	Sample	853:858	arg1	preparation					860:870	Sample preparation	853:870	Sample preparation	853:870	Sample preparation, quantitative LC-tandem MS (LC-MS/MS) analysis, and data processing methods are provided.
32681150	5	63	theme	chromatography-mass	807:825	arg1	nanoLC-MS					841:849	nanoLC-MS	841:849	nanoLC-MS	841:849	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	5	63	theme	chromatography-mass	807:825	arg1	spectrometry					827:838	nanoflow liquid chromatography-mass spectrometry	791:838	nanoflow liquid chromatography-mass spectrometry (nanoLC-MS)	791:850	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	6	64	theme	LC-MS/MS	900:907	arg1	analysis					910:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	Sample preparation, quantitative LC-tandem MS (LC-MS/MS) analysis, and data processing methods are provided.
32681150	4	65	theme	intact	652:657	arg1	glycolipids					659:669	intact glycolipids	652:669	intact glycolipids in parallel	652:681	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	4	66	from	N-glycans	599:607	arg1	parallel					674:681	parallel	674:681	parallel	674:681	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	7	67	theme	membrane	1057:1064	arg1	proteins					1066:1073	membrane proteins	1057:1073	membrane proteins	1057:1073	In addition, we discuss glycoproteomic analysis that yields the site-specific glycosylation of membrane proteins.
32681150	9	68	theme	2-3	1319:1321	arg1	d					1323:1323	2-3 d	1319:1323	2-3 d	1319:1323	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	12	69	theme	studies	1785:1791	arg1	therapeutics					1841:1852	therapeutics	1841:1852	therapeutics	1841:1852	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	69	theme	studies	1785:1791	arg1	range					1743:1747	a broad range	1735:1747	a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics	1735:1852	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	12	69	theme	studies	1785:1791	arg1	discovery					1827:1835	glycan-based biomarker discovery	1804:1835	glycan-based biomarker discovery	1804:1835	The ability to quantitate individual glycoforms and glycoconjugates will find utility in a broad range of fundamental and applied clinical studies, including glycan-based biomarker discovery and therapeutics.
32681150	9	70	theme	sample	1422:1427	arg1	sizes					1429:1433	different sample sizes	1412:1433	different sample sizes	1412:1433	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	5	71	theme	liquid	800:805	arg1	nanoLC-MS					841:849	nanoLC-MS	841:849	nanoLC-MS	841:849	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	5	71	theme	liquid	800:805	arg1	spectrometry					827:838	nanoflow liquid chromatography-mass spectrometry	791:838	nanoflow liquid chromatography-mass spectrometry (nanoLC-MS)	791:850	Profiling of the glycans and the glycolipids is performed using nanoflow liquid chromatography-mass spectrometry (nanoLC-MS).
32681150	6	72	theme	MS	896:897	arg1	analysis					910:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	quantitative LC-tandem MS (LC-MS/MS) analysis	873:917	Sample preparation, quantitative LC-tandem MS (LC-MS/MS) analysis, and data processing methods are provided.
32681150	9	73	theme	sample	1286:1291	arg1	preparation					1293:1303	The sample preparation	1282:1303	The sample preparation process	1282:1311	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	7	74	theme	proteins	1066:1073	arg1	glycosylation					1040:1052	the site-specific glycosylation	1022:1052	the site-specific glycosylation of membrane proteins	1022:1073	In addition, we discuss glycoproteomic analysis that yields the site-specific glycosylation of membrane proteins.
32681150	4	75	theme	same	694:697	arg1	fraction					717:724	the same enriched membrane fraction	690:724	the same enriched membrane fraction	690:724	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	0	76	theme	cells	74:78	arg1	glycocalyxes					58:69	the glycocalyxes	54:69	the glycocalyxes of cells and tissues	54:90	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.
32681150	0	77	theme	glycomic	25:32	arg1	characterization					34:49	Comprehensive structural glycomic characterization	0:49	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.	0:91	Comprehensive structural glycomic characterization of the glycocalyxes of cells and tissues.
32681150	9	78	theme	different	1412:1420	arg1	sizes					1429:1433	different sample sizes	1412:1433	different sample sizes	1412:1433	The sample preparation process takes 2-3 d, whereas the time spent on instrumental and data analyses could vary from 1 to 5 d for different sample sizes.
32681150	8	79	theme	glycolipid	1139:1148	arg1	analyses					1150:1157	N-glycan, O-glycan, and glycolipid analyses	1115:1157	N-glycan, O-glycan, and glycolipid analyses	1115:1157	To reduce the amount of sample needed, N-glycan, O-glycan, and glycolipid analyses are performed on the same enriched fraction, whereas glycoproteomic analysis is performed on a separate enriched fraction.
32681150	4	80	theme	glycolipids	659:669	arg1	O-glycans					613:621	the glycocalyx N-glycans and O-glycans	584:621	O-glycans	613:621	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
32681150	4	80	theme	glycolipids	659:669	arg1	N-glycans					599:607	the glycocalyx N-glycans and O-glycans	584:621	N-glycans	599:607	This protocol describes how to comprehensively characterize the glycocalyx N-glycans and O-glycans of glycoproteins, as well as intact glycolipids in parallel, using the same enriched membrane fraction.
34174425	14	0	theme	complex	2558:2564	arg1	structures					2586:2595	more complex human-like N-glycan structures	2553:2595	more complex human-like N-glycan structures	2553:2595	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	10	1	theme	glycan	1840:1845	arg1	structure					1847:1855	the growing ER glycan structure	1825:1855	the growing ER glycan structure	1825:1855	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	3	2	theme	undesirable	522:532	arg1	reactions					541:549	undesirable immune reactions	522:549	undesirable immune reactions	522:549	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	9	3	theme	glycan	1609:1614	arg1	structures					1616:1625	glycan structures	1609:1625	glycan structures	1609:1625	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	9	4	theme	N-glycan	1400:1407	arg1	structures					1409:1418	the N-glycan structures	1396:1418	the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases,	1396:1520	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	12	5	theme	new	2079:2081	arg1	structures					2105:2114	large N-glycan structures	2090:2114	large N-glycan structures	2090:2114	Without the glucose caps, a new set of large N-glycan structures was formed.
34174425	12	5	theme	new	2079:2081	arg1	set					2083:2085	a new set	2077:2085	a new set of large N-glycan structures	2077:2114	Without the glucose caps, a new set of large N-glycan structures was formed.
34174425	8	6	with	combination	1222:1232	arg1	treatments					1269:1278	chemical glycan treatments	1253:1278	chemical glycan treatments	1253:1278	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	8	6	with	combination	1222:1232	arg1	enzymatic					1239:1247	enzymatic	1239:1247	enzymatic	1239:1247	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	8	7	used	used	1199:1202	arg2	we					1191:1192	we	1191:1192	we	1191:1192	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	10	8	theme	homolog	1718:1724	arg1	glucosyltransferase					1766:1784	the putative α-1,3- glucosyltransferase	1746:1784	the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure	1746:1855	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	10	8	theme	homolog	1718:1724	arg1	algF					1726:1729	the ALG6 homolog algF	1709:1729	the ALG6 homolog algF	1709:1729	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	11	9	theme	heterodimeric	2011:2023	arg1	complex					2042:2048	the heterodimeric α-glucosidase II complex	2007:2048	the heterodimeric α-glucosidase II complex	2007:2048	Similarly, these structures are also sensitive to overexpression of the genes encoding the heterodimeric α-glucosidase II complex.
34174425	12	10	theme	glucose	2063:2069	arg1	caps					2071:2074	the glucose caps	2059:2074	the glucose caps	2059:2074	Without the glucose caps, a new set of large N-glycan structures was formed.
34174425	10	11	theme	Hex6-7HexNAc2	1894:1906	arg1	structures					1908:1917	Hex6-7HexNAc2 structures	1894:1917	Hex6-7HexNAc2 structures	1894:1917	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	5	12	theme	structures	826:835	arg1	accumulation					791:802	the accumulation	787:802	the accumulation of Man5GlcNAc2 glycan structures that can act as a precursor for remodeling	787:878	In yeast, deletion of ALG3 leads to the accumulation of Man5GlcNAc2 glycan structures that can act as a precursor for remodeling.
34174425	6	13	theme	homolog	926:932	arg1	algC					934:937	the ALG3 homolog algC	917:937	the ALG3 homolog algC	917:937	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	8	14	from	deletions	1209:1217	arg1	combination					1222:1232	combination	1222:1232	combination with enzymatic and chemical glycan treatments	1222:1278	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	1	15	theme	therapeutic	223:233	arg1	proteins					235:242	therapeutic proteins	223:242	therapeutic proteins	223:242	Filamentous fungi secrete protein with a very high efficiency, and this potential can be exploited advantageously to produce therapeutic proteins at low costs.
34174425	14	16	theme	further	2514:2520	arg1	engineering					2522:2532	further engineering	2514:2532	further engineering	2514:2532	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	8	17	theme	chemical	1253:1260	arg1	treatments					1269:1278	chemical glycan treatments	1253:1278	chemical glycan treatments	1253:1278	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	14	18	from	processing	2331:2340	arg1	nidulans					2348:2355	A. nidulans	2345:2355	A. nidulans	2345:2355	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	2	19	theme	significant	260:270	arg1	barrier					272:278	A significant barrier	258:278	A significant barrier to this goal	258:291	A significant barrier to this goal is posed by the fact that fungal N-glycosylation varies substantially from that of humans.
34174425	1	20	theme	high	144:147	arg1	efficiency					149:158	a very high efficiency	137:158	a very high efficiency	137:158	Filamentous fungi secrete protein with a very high efficiency, and this potential can be exploited advantageously to produce therapeutic proteins at low costs.
34174425	0	21	theme	humanized	67:75	arg1	structures					86:95	humanized N-glycan structures	67:95	humanized N-glycan structures	67:95	Glycoengineering of Aspergillus nidulans to produce precursors for humanized N-glycan structures.
34174425	10	22	theme	putative	1750:1757	arg1	glucosyltransferase					1766:1784	the putative α-1,3- glucosyltransferase	1746:1784	the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure	1746:1855	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	10	22	theme	putative	1750:1757	arg1	algF					1726:1729	the ALG6 homolog algF	1709:1729	the ALG6 homolog algF	1709:1729	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	9	23	theme	any	1480:1482	arg1	devoid					1470:1475	devoid	1470:1475	devoid	1470:1475	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	9	23	theme	any	1480:1482	arg1	strain					1453:1458	a mutant A. nidulans strain	1432:1458	a mutant A. nidulans strain	1432:1458	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	8	24	theme	model	1318:1322	arg1	nidulans					1343:1350	the model fungus Aspergillus nidulans	1314:1350	the model fungus Aspergillus nidulans	1314:1350	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	9	25	theme	ER	1497:1498	arg1	transferases					1508:1519	the known ER mannose transferases	1487:1519	the known ER mannose transferases	1487:1519	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	6	26	contain	contain	1002:1008	arg1	majority					975:982	the majority	971:982	the majority of the structures	971:1000	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	6	26	contain	contain	1002:1008	arg2	residues					1022:1029	more hexose residues	1010:1029	more hexose residues	1010:1029	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	8	27	theme	Aspergillus	1331:1341	arg1	nidulans					1343:1350	the model fungus Aspergillus nidulans	1314:1350	the model fungus Aspergillus nidulans	1314:1350	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	8	28	gly	N-glycosylation	1295:1309	arg1	nidulans					1343:1350	the model fungus Aspergillus nidulans	1314:1350	the model fungus Aspergillus nidulans	1314:1350	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	3	29	theme	Inappropriate	384:396	arg1	N-glycosylation					398:412	Inappropriate N-glycosylation	384:412	Inappropriate N-glycosylation of therapeutics	384:428	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	3	30	theme	reduced	441:447	arg1	quality					457:463	reduced product quality	441:463	reduced product quality	441:463	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	7	31	theme	additional	1131:1140	arg1	optimization					1149:1160	additional strain optimization	1131:1160	additional strain optimization	1131:1160	Hence, additional strain optimization is required.
34174425	6	32	theme	more	1010:1013	arg1	residues					1022:1029	more hexose residues	1010:1029	more hexose residues	1010:1029	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	10	33	theme	first	1800:1804	arg1	residue					1814:1820	the first glucose residue	1796:1820	the first glucose residue	1796:1820	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	0	34	theme	Aspergillus	20:30	arg1	nidulans					32:39	Aspergillus nidulans	20:39	Aspergillus nidulans	20:39	Glycoengineering of Aspergillus nidulans to produce precursors for humanized N-glycan structures.
34174425	5	35	theme	ALG3	773:776	arg1	deletion					761:768	deletion	761:768	deletion of ALG3	761:776	In yeast, deletion of ALG3 leads to the accumulation of Man5GlcNAc2 glycan structures that can act as a precursor for remodeling.
34174425	14	36	theme	glycoforms	2433:2442	arg1	%					2424:2424	more than 70%	2412:2424	more than 70% of the glycoforms	2412:2442	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	14	36	theme	glycoforms	2433:2442	arg1	glycoforms					2433:2442	the glycoforms	2429:2442	the glycoforms	2429:2442	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	9	37	theme	desirable	1542:1550	arg1	structures					1571:1580	desirable Man3GlcNAc2 glycan structures	1542:1580	desirable Man3GlcNAc2 glycan structures	1542:1580	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	6	38	theme	structures	991:1000	arg1	majority					975:982	the majority	971:982	the majority of the structures	971:1000	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	9	39	theme	In	1353:1354	arg1	analyses					1362:1369	In vitro analyses	1353:1369	In vitro analyses	1353:1369	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	10	40	with	agreement	1671:1679	arg1	view					1691:1694	this view	1686:1694	this view	1686:1694	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	9	41	theme	glycan	1564:1569	arg1	structures					1571:1580	desirable Man3GlcNAc2 glycan structures	1542:1580	desirable Man3GlcNAc2 glycan structures	1542:1580	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	12	42	theme	N-glycan	2096:2103	arg1	structures					2105:2114	large N-glycan structures	2090:2114	large N-glycan structures	2090:2114	Without the glucose caps, a new set of large N-glycan structures was formed.
34174425	2	43	theme	fungal	319:324	arg1	N-glycosylation					326:340	fungal N-glycosylation	319:340	fungal N-glycosylation	319:340	A significant barrier to this goal is posed by the fact that fungal N-glycosylation varies substantially from that of humans.
34174425	5	44	theme	Man5GlcNAc2	807:817	arg1	structures					826:835	Man5GlcNAc2 glycan structures	807:835	Man5GlcNAc2 glycan structures that can act as a precursor for remodeling	807:878	In yeast, deletion of ALG3 leads to the accumulation of Man5GlcNAc2 glycan structures that can act as a precursor for remodeling.
34174425	5	44	theme	Man5GlcNAc2	807:817	arg1	precursor					855:863	a precursor	853:863	a precursor for remodeling	853:878	In yeast, deletion of ALG3 leads to the accumulation of Man5GlcNAc2 glycan structures that can act as a precursor for remodeling.
34174425	3	45	theme	immune	534:539	arg1	reactions					541:549	undesirable immune reactions	522:549	undesirable immune reactions	522:549	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	1	46	theme	low	247:249	arg1	costs					251:255	low costs	247:255	low costs	247:255	Filamentous fungi secrete protein with a very high efficiency, and this potential can be exploited advantageously to produce therapeutic proteins at low costs.
34174425	9	47	theme	substantial	1586:1596	arg1	amounts					1598:1604	substantial amounts	1586:1604	substantial amounts of glycan structures	1586:1625	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	9	47	theme	substantial	1586:1596	arg1	structures					1616:1625	glycan structures	1609:1625	glycan structures	1609:1625	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	14	48	theme	human-like	2566:2575	arg1	structures					2586:2595	more complex human-like N-glycan structures	2553:2595	more complex human-like N-glycan structures	2553:2595	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	4	49	theme	fungi	638:642	arg1	pathway					615:621	the glycosylation pathway	597:621	the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans	597:748	One solution to this problem is to reprogram the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans.
34174425	14	50	theme	N-glycan	2322:2329	arg1	processing					2331:2340	the N-glycan processing	2318:2340	the N-glycan processing in A. nidulans	2318:2355	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	10	51	theme	ER	1837:1838	arg1	structure					1847:1855	the growing ER glycan structure	1825:1855	the growing ER glycan structure	1825:1855	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	9	52	theme	structures	1616:1625	arg1	amounts					1598:1604	substantial amounts	1586:1604	substantial amounts of glycan structures	1586:1625	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	9	52	theme	structures	1616:1625	arg1	structures					1616:1625	glycan structures	1609:1625	glycan structures	1609:1625	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	4	53	theme	glycosylation	601:613	arg1	pathway					615:621	the glycosylation pathway	597:621	the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans	597:748	One solution to this problem is to reprogram the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans.
34174425	14	54	theme	new	2300:2302	arg1	insights					2304:2311	our new insights	2296:2311	our new insights into the N-glycan processing in A. nidulans	2296:2355	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	14	55	theme	mutant	2373:2378	arg1	strain					2380:2385	an A. nidulans mutant strain	2358:2385	an A. nidulans mutant strain	2358:2385	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	10	56	theme	algF	1726:1729	arg1	deletion					1697:1704	deletion	1697:1704	deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure,	1697:1856	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	8	57	theme	gene	1204:1207	arg1	deletions					1209:1217	gene deletions	1204:1217	gene deletions in combination with enzymatic and chemical glycan treatments	1204:1278	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	10	58	theme	structures	1908:1917	arg1	structures					1908:1917	Hex6-7HexNAc2 structures	1894:1917	Hex6-7HexNAc2 structures	1894:1917	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	10	58	theme	structures	1908:1917	arg1	amounts					1883:1889	the amounts	1879:1889	the amounts of Hex6-7HexNAc2 structures	1879:1917	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	10	59	theme	ALG6	1713:1716	arg1	glucosyltransferase					1766:1784	the putative α-1,3- glucosyltransferase	1746:1784	the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure	1746:1855	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	10	59	theme	ALG6	1713:1716	arg1	algF					1726:1729	the ALG6 homolog algF	1709:1729	the ALG6 homolog algF	1709:1729	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	9	60	theme	mutant	1434:1439	arg1	devoid					1470:1475	devoid	1470:1475	devoid	1470:1475	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	9	60	theme	mutant	1434:1439	arg1	strain					1453:1458	a mutant A. nidulans strain	1432:1458	a mutant A. nidulans strain	1432:1458	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	11	61	theme	genes	1992:1996	arg1	overexpression					1970:1983	overexpression	1970:1983	overexpression of the genes encoding the heterodimeric α-glucosidase II complex	1970:2048	Similarly, these structures are also sensitive to overexpression of the genes encoding the heterodimeric α-glucosidase II complex.
34174425	6	62	theme	algC	934:937	arg1	deletion					905:912	deletion	905:912	deletion of the ALG3 homolog algC	905:937	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	9	63	theme	glucose	1650:1656	arg1	residues					1658:1665	glucose residues	1650:1665	glucose residues	1650:1665	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	6	64	theme	glycan	1105:1110	arg1	structures					1112:1121	humanized glycan structures	1095:1121	humanized glycan structures	1095:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	13	65	theme	mannosidase	2240:2250	arg1	activity					2252:2259	mannosidase activity	2240:2259	mannosidase activity	2240:2259	Formation of this set is mostly, perhaps entirely, due to mannosylation, as overexpression of the gene encoding mannosidase activity led to their elimination.
34174425	6	66	theme	ALG3	921:924	arg1	algC					934:937	the ALG3 homolog algC	917:937	the ALG3 homolog algC	917:937	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	8	67	theme	glycan	1262:1267	arg1	treatments					1269:1278	chemical glycan treatments	1253:1278	chemical glycan treatments	1253:1278	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	3	68	theme	decreased	491:499	arg1	half-life					507:515	decreased serum half-life	491:515	decreased serum half-life	491:515	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	0	69	theme	N-glycan	77:84	arg1	structures					86:95	humanized N-glycan structures	67:95	humanized N-glycan structures	67:95	Glycoengineering of Aspergillus nidulans to produce precursors for humanized N-glycan structures.
34174425	10	70	theme	α-1,3-	1759:1764	arg1	glucosyltransferase					1766:1784	the putative α-1,3- glucosyltransferase	1746:1784	the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure	1746:1855	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	10	70	theme	α-1,3-	1759:1764	arg1	algF					1726:1729	the ALG6 homolog algF	1709:1729	the ALG6 homolog algF	1709:1729	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	5	71	theme	glycan	819:824	arg1	structures					826:835	Man5GlcNAc2 glycan structures	807:835	Man5GlcNAc2 glycan structures that can act as a precursor for remodeling	807:878	In yeast, deletion of ALG3 leads to the accumulation of Man5GlcNAc2 glycan structures that can act as a precursor for remodeling.
34174425	5	71	theme	glycan	819:824	arg1	precursor					855:863	a precursor	853:863	a precursor for remodeling	853:878	In yeast, deletion of ALG3 leads to the accumulation of Man5GlcNAc2 glycan structures that can act as a precursor for remodeling.
34174425	14	72	theme	Man3-5GlcNAc2	2457:2469	arg1	species					2471:2477	Man3-5GlcNAc2 species	2457:2477	Man3-5GlcNAc2 species	2457:2477	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	14	73	dep	A.	2361:2362	arg1	nidulans					2364:2371	nidulans	2364:2371	nidulans	2364:2371	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	11	74	theme	α-glucosidase	2025:2037	arg1	complex					2042:2048	the heterodimeric α-glucosidase II complex	2007:2048	the heterodimeric α-glucosidase II complex	2007:2048	Similarly, these structures are also sensitive to overexpression of the genes encoding the heterodimeric α-glucosidase II complex.
34174425	9	75	theme	known	1491:1495	arg1	transferases					1508:1519	the known ER mannose transferases	1487:1519	the known ER mannose transferases	1487:1519	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	13	76	theme	gene	2226:2229	arg1	overexpression					2204:2217	overexpression	2204:2217	overexpression of the gene encoding mannosidase activity	2204:2259	Formation of this set is mostly, perhaps entirely, due to mannosylation, as overexpression of the gene encoding mannosidase activity led to their elimination.
34174425	6	77	theme	N-glycan	951:958	arg1	pool					960:963	an N-glycan pool	948:963	an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures	948:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	6	77	theme	N-glycan	951:958	arg1	substrates					1080:1089	substrates	1080:1089	substrates for humanized glycan structures	1080:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	6	77	theme	N-glycan	951:958	arg1	species					1054:1060	the Man3-5GlcNAc2 species	1036:1060	the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures	1036:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	9	78	dep	In	1353:1354	arg1	vitro					1356:1360	vitro	1356:1360	vitro	1356:1360	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	3	79	gly	N-glycosylation	398:412	arg1	therapeutics					417:428	therapeutics	417:428	therapeutics	417:428	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	9	80	theme	A.	1441:1442	arg1	devoid					1470:1475	devoid	1470:1475	devoid	1470:1475	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	9	80	theme	A.	1441:1442	arg1	strain					1453:1458	a mutant A. nidulans strain	1432:1458	a mutant A. nidulans strain	1432:1458	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	9	81	theme	mannose	1500:1506	arg1	transferases					1508:1519	the known ER mannose transferases	1487:1519	the known ER mannose transferases	1487:1519	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	6	82	theme	Man3-5GlcNAc2	1040:1052	arg1	pool					960:963	an N-glycan pool	948:963	an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures	948:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	6	82	theme	Man3-5GlcNAc2	1040:1052	arg1	substrates					1080:1089	substrates	1080:1089	substrates for humanized glycan structures	1080:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	6	82	theme	Man3-5GlcNAc2	1040:1052	arg1	species					1054:1060	the Man3-5GlcNAc2 species	1036:1060	the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures	1036:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	8	83	theme	fungus	1324:1329	arg1	nidulans					1343:1350	the model fungus Aspergillus nidulans	1314:1350	the model fungus Aspergillus nidulans	1314:1350	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	7	84	theme	strain	1142:1147	arg1	optimization					1149:1160	additional strain optimization	1131:1160	additional strain optimization	1131:1160	Hence, additional strain optimization is required.
34174425	8	85	from	N-glycosylation	1295:1309	arg1	nidulans					1343:1350	the model fungus Aspergillus nidulans	1314:1350	the model fungus Aspergillus nidulans	1314:1350	In this report, we have used gene deletions in combination with enzymatic and chemical glycan treatments to investigate N-glycosylation in the model fungus Aspergillus nidulans.
34174425	1	86	theme	Filamentous	98:108	arg1	fungi					110:114	Filamentous fungi	98:114	Filamentous fungi	98:114	Filamentous fungi secrete protein with a very high efficiency, and this potential can be exploited advantageously to produce therapeutic proteins at low costs.
34174425	3	87	theme	product	449:455	arg1	quality					457:463	reduced product quality	441:463	reduced product quality	441:463	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	0	88	theme	nidulans	32:39	arg1	Glycoengineering					0:15	Glycoengineering	0:15	Glycoengineering of Aspergillus nidulans	0:39	Glycoengineering of Aspergillus nidulans to produce precursors for humanized N-glycan structures.
34174425	6	89	theme	hexose	1015:1020	arg1	residues					1022:1029	more hexose residues	1010:1029	more hexose residues	1010:1029	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	10	90	theme	glucose	1806:1812	arg1	residue					1814:1820	the first glucose residue	1796:1820	the first glucose residue	1796:1820	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	14	91	theme	A.	2361:2362	arg1	strain					2380:2385	an A. nidulans mutant strain	2358:2385	an A. nidulans mutant strain	2358:2385	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	3	92	theme	poor	476:479	arg1	efficacy					481:488	poor efficacy	476:488	poor efficacy	476:488	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	13	93	theme	set	2146:2148	arg1	Formation					2128:2136	Formation	2128:2136	Formation of this set	2128:2148	Formation of this set is mostly, perhaps entirely, due to mannosylation, as overexpression of the gene encoding mannosidase activity led to their elimination.
34174425	9	94	theme	Man3GlcNAc2	1552:1562	arg1	structures					1571:1580	desirable Man3GlcNAc2 glycan structures	1542:1580	desirable Man3GlcNAc2 glycan structures	1542:1580	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
34174425	6	95	theme	humanized	1095:1103	arg1	structures					1112:1121	humanized glycan structures	1095:1121	humanized glycan structures	1095:1121	However, in Aspergilli, deletion of the ALG3 homolog algC leads to an N-glycan pool where the majority of the structures contain more hexose residues than the Man3-5GlcNAc2 species that can serve as substrates for humanized glycan structures.
34174425	3	96	theme	therapeutics	417:428	arg1	N-glycosylation					398:412	Inappropriate N-glycosylation	384:412	Inappropriate N-glycosylation of therapeutics	384:428	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	10	97	theme	growing	1829:1835	arg1	structure					1847:1855	the growing ER glycan structure	1825:1855	the growing ER glycan structure	1825:1855	In agreement with this view, deletion of the ALG6 homolog algF, which encodes the putative α-1,3- glucosyltransferase that adds the first glucose residue to the growing ER glycan structure, dramatically reduces the amounts of Hex6-7HexNAc2 structures.
34174425	12	98	theme	structures	2105:2114	arg1	structures					2105:2114	large N-glycan structures	2090:2114	large N-glycan structures	2090:2114	Without the glucose caps, a new set of large N-glycan structures was formed.
34174425	12	98	theme	structures	2105:2114	arg1	set					2083:2085	a new set	2077:2085	a new set of large N-glycan structures	2077:2114	Without the glucose caps, a new set of large N-glycan structures was formed.
34174425	4	99	theme	filamentous	626:636	arg1	fungi					638:642	filamentous fungi	626:642	filamentous fungi	626:642	One solution to this problem is to reprogram the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans.
34174425	4	100	with	proteins	656:663	arg1	those					716:720	those	716:720	those	716:720	One solution to this problem is to reprogram the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans.
34174425	4	100	with	proteins	656:663	arg1	glycans					670:676	glycans	670:676	glycans that match, or can be remodeled into	670:713	One solution to this problem is to reprogram the glycosylation pathway of filamentous fungi to decorate proteins with glycans that match, or can be remodeled into, those that are accepted by humans.
34174425	12	101	theme	large	2090:2094	arg1	structures					2105:2114	large N-glycan structures	2090:2114	large N-glycan structures	2090:2114	Without the glucose caps, a new set of large N-glycan structures was formed.
34174425	3	102	theme	serum	501:505	arg1	half-life					507:515	decreased serum half-life	491:515	decreased serum half-life	491:515	Inappropriate N-glycosylation of therapeutics results in reduced product quality, including poor efficacy, decreased serum half-life, and undesirable immune reactions.
34174425	14	103	theme	N-glycan	2577:2584	arg1	structures					2586:2595	more complex human-like N-glycan structures	2553:2595	more complex human-like N-glycan structures	2553:2595	Based on our new insights into the N-glycan processing in A. nidulans, an A. nidulans mutant strain was constructed in which more than 70% of the glycoforms appear to be Man3-5GlcNAc2 species, which may serve as precursors for further engineering in order to create more complex human-like N-glycan structures.
34174425	9	104	dep	A.	1441:1442	arg1	nidulans					1444:1451	nidulans	1444:1451	nidulans	1444:1451	In vitro analyses showed that only some of the N-glycan structures produced by a mutant A. nidulans strain, which is devoid of any of the known ER mannose transferases, can be trimmed into desirable Man3GlcNAc2 glycan structures, as substantial amounts of glycan structures appear to be capped by glucose residues.
35026558	8	0	theme	saccharide	1477:1486	arg1	useful					1529:1534	useful	1529:1534	useful	1529:1534	The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
35026558	8	0	theme	saccharide	1477:1486	arg1	primers					1488:1494	The saccharide primers	1473:1494	The saccharide primers developed in this study	1473:1518	The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
35026558	6	1	theme	glycosylated	1137:1148	arg1	products					1150:1157	the glycosylated products	1133:1157	the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis	1133:1242	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	3	2	theme	human	580:584	arg1	MKN45 cells					601:611	human gastric cancer MKN45 cells	580:611	human gastric cancer MKN45 cells	580:611	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	4	3	theme	saccharide	871:880	arg1	primers					882:888	the saccharide primers	867:888	the saccharide primers	867:888	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	0	4	theme	GalNAc-Ser	79:88	arg1	residues					105:112	GalNAc-Ser and GalNAc-Thr residues	79:112	GalNAc-Ser and GalNAc-Thr residues	79:112	In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
35026558	3	5	theme	gastric	586:592	arg1	MKN45 cells					601:611	human gastric cancer MKN45 cells	580:611	human gastric cancer MKN45 cells	580:611	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	5	6	dep	in	904:905	arg1	vitro					907:911	vitro	907:911	vitro	907:911	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	1	7	dep	serine	145:150	arg1	residue					165:171	residue	165:171	residue	165:171	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	4	8	theme	acid	850:853	arg1	residues					855:862	the amino acid residues	840:862	the amino acid residues in the saccharide primers	840:888	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	0	9	theme	GalNAc-Thr	94:103	arg1	residues					105:112	GalNAc-Ser and GalNAc-Thr residues	79:112	GalNAc-Ser and GalNAc-Thr residues	79:112	In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
35026558	6	10	theme	cell	1299:1302	arg1	experiments					1304:1314	the cell experiments	1295:1314	the cell experiments	1295:1314	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	4	11	theme	glycosylated	800:811	arg1	products					813:820	glycosylated products	800:820	glycosylated products	800:820	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	6	12	theme	amino	1260:1264	arg1	selectivity					1271:1281	the same amino acid selectivity	1251:1281	the same amino acid selectivity	1251:1281	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	5	13	theme	antigen	928:934	arg1	synthesis					913:921	in vitro synthesis	904:921	in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc)	904:1023	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	4	14	theme	amino	844:848	arg1	residues					855:862	the amino acid residues	840:862	the amino acid residues in the saccharide primers	840:888	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	2	15	theme	alkyl	276:280	arg1	glycosides					282:291	two novel alkyl glycosides	266:291	two novel alkyl glycosides	266:291	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	15	theme	alkyl	276:280	arg1	-l-serineamide					348:361	-l-serineamide	348:361	-l-serineamide	348:361	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	15	theme	alkyl	276:280	arg1	-l-threonineamide					438:454	-l-threonineamide	438:454	-l-threonineamide	438:454	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	15	theme	alkyl	276:280	arg1	primers					504:510	saccharide primers	493:510	saccharide primers to prime mucin-type O-glycan biosynthesis in cells	493:561	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	8	16	from	oligosaccharides	1561:1576	arg1	cells					1581:1585	cells	1581:1585	cells	1581:1585	The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
35026558	5	17	dep	preferred	1025:1033	arg1	whereas					1053:1059	whereas	1053:1059	whereas	1053:1059	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	6	18	attach	derived	1159:1165	arg1	GalNAc-Ser/Thr-C12					1172:1189	GalNAc-Ser/Thr-C12	1172:1189	GalNAc-Ser/Thr-C12	1172:1189	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	6	18	attach	derived	1159:1165	arg1	Gal-GalNAc-Ser/Thr-C12					1195:1216	Gal-GalNAc-Ser/Thr-C12	1195:1216	Gal-GalNAc-Ser/Thr-C12	1195:1216	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	6	18	attach	derived	1159:1165	arg2	products					1150:1157	the glycosylated products	1133:1157	the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis	1133:1242	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	4	19	from	residues	855:862	arg1	primers					882:888	the saccharide primers	867:888	the saccharide primers	867:888	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	2	20	theme	novel	270:274	arg1	glycosides					282:291	two novel alkyl glycosides	266:291	two novel alkyl glycosides	266:291	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	20	theme	novel	270:274	arg1	-l-serineamide					348:361	-l-serineamide	348:361	-l-serineamide	348:361	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	20	theme	novel	270:274	arg1	-l-threonineamide					438:454	-l-threonineamide	438:454	-l-threonineamide	438:454	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	20	theme	novel	270:274	arg1	primers					504:510	saccharide primers	493:510	saccharide primers to prime mucin-type O-glycan biosynthesis in cells	493:561	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	21	theme	prime	515:519	arg1	biosynthesis					541:552	prime mucin-type O-glycan biosynthesis	515:552	prime mucin-type O-glycan biosynthesis in cells	515:561	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	22	from	biosynthesis	541:552	arg1	cells					557:561	cells	557:561	cells	557:561	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	3	23	theme	glycosylated	645:656	arg1	products					658:665	22 glycosylated products	642:665	22 glycosylated products	642:665	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	5	24	theme	fucosyl-T	953:961	arg1	synthesis					913:921	in vitro synthesis	904:921	in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc)	904:1023	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	0	25	theme	In	0:1	arg1	synthesis					9:17	In vitro synthesis	0:17	In vitro synthesis of mucin-type O-glycans	0:41	In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
35026558	1	26	from	O-glycosylation	126:140	arg1	proteins					176:183	proteins	176:183	proteins	176:183	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	2	27	dep	-l-serineamide	348:361	arg1	GalNAc-Ser-C12					364:377	GalNAc-Ser-C12	364:377	GalNAc-Ser-C12	364:377	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	6	28	gly	glycosylated	1137:1148	arg1	products					1150:1157	the glycosylated products	1133:1157	the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis	1133:1242	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	5	29	theme	serine	1037:1042	arg1	residue					1044:1050	a serine residue	1035:1050	a serine residue	1035:1050	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	8	30	theme	mucin-type	1550:1559	arg1	oligosaccharides					1561:1576	mucin-type oligosaccharides	1550:1576	mucin-type oligosaccharides in cells	1550:1585	The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
35026558	5	31	theme	T	926:926	arg1	Galβ1-3GalNAc					937:949	Galβ1-3GalNAc	937:949	Galβ1-3GalNAc	937:949	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	5	31	theme	T	926:926	arg1	antigen					928:934	T antigen	926:934	T antigen (Galβ1-3GalNAc)	926:950	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	2	32	theme	saccharide	493:502	arg1	glycosides					282:291	two novel alkyl glycosides	266:291	two novel alkyl glycosides	266:291	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	2	32	theme	saccharide	493:502	arg1	primers					504:510	saccharide primers	493:510	saccharide primers to prime mucin-type O-glycan biosynthesis in cells	493:561	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	1	33	gly	O-glycosylation	126:140	arg1	serine					145:150	serine	145:150	serine	145:150	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	1	33	gly	O-glycosylation	126:140	arg1	threonine					155:163	threonine	155:163	threonine	155:163	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	1	33	gly	O-glycosylation	126:140	arg1	proteins					176:183	proteins	176:183	proteins	176:183	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	3	34	theme	chromatography-mass	730:748	arg1	spectrometry					750:761	liquid chromatography-mass spectrometry	723:761	liquid chromatography-mass spectrometry	723:761	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	1	35	theme	Mucin-type	115:124	arg1	O-glycosylation					126:140	Mucin-type O-glycosylation	115:140	Mucin-type O-glycosylation of serine or threonine residue in proteins	115:183	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	3	36	theme	cancer	594:599	arg1	MKN45 cells					601:611	human gastric cancer MKN45 cells	580:611	human gastric cancer MKN45 cells	580:611	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	0	37	theme	O-glycans	33:41	arg1	synthesis					9:17	In vitro synthesis	0:17	In vitro synthesis of mucin-type O-glycans	0:41	In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
35026558	4	38	theme	products	813:820	arg1	dependent					827:835	dependent	827:835	dependent	827:835	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	4	38	theme	products	813:820	arg1	amounts					789:795	The amounts	785:795	The amounts of glycosylated products	785:820	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	4	38	theme	products	813:820	arg1	products					813:820	glycosylated products	800:820	glycosylated products	800:820	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	6	39	theme	same	1255:1258	arg1	selectivity					1271:1281	the same amino acid selectivity	1251:1281	the same amino acid selectivity	1251:1281	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	5	40	theme	threonine	1101:1109	arg1	residue					1111:1117	a threonine residue	1099:1117	a threonine residue	1099:1117	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	0	41	theme	mucin-type	22:31	arg1	O-glycans					33:41	mucin-type O-glycans	22:41	mucin-type O-glycans	22:41	In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
35026558	8	42	theme	cell	1639:1642	arg1	function					1644:1651	cell function	1639:1651	cell function	1639:1651	The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
35026558	1	43	theme	major	211:215	arg1	modifications					236:248	the major post-translational modifications	207:248	the major post-translational modifications	207:248	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	2	44	theme	O-glycan	532:539	arg1	biosynthesis					541:552	prime mucin-type O-glycan biosynthesis	515:552	prime mucin-type O-glycan biosynthesis in cells	515:561	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	3	45	theme	liquid	723:728	arg1	spectrometry					750:761	liquid chromatography-mass spectrometry	723:761	liquid chromatography-mass spectrometry	723:761	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	5	46	theme	sialyl-T	991:998	arg1	synthesis					913:921	in vitro synthesis	904:921	in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc)	904:1023	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
35026558	2	47	theme	mucin-type	521:530	arg1	biosynthesis					541:552	prime mucin-type O-glycan biosynthesis	515:552	prime mucin-type O-glycan biosynthesis in cells	515:561	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	7	48	theme	amino	1431:1435	arg1	residues					1442:1449	amino acid residues	1431:1449	amino acid residues conjugated to GalNAc	1431:1470	These results indicate that glycosyltransferases involved in the biosynthesis of mucin-type O-glycans distinguish amino acid residues conjugated to GalNAc.
35026558	3	49	gly	glycosylated	645:656	arg1	products					658:665	22 glycosylated products	642:665	22 glycosylated products	642:665	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	7	50	theme	mucin-type	1398:1407	arg1	O-glycans					1409:1417	mucin-type O-glycans	1398:1417	mucin-type O-glycans	1398:1417	These results indicate that glycosyltransferases involved in the biosynthesis of mucin-type O-glycans distinguish amino acid residues conjugated to GalNAc.
35026558	2	51	dep	-l-threonineamide	438:454	arg1	GalNAc-Thr-C12					457:470	GalNAc-Thr-C12	457:470	GalNAc-Thr-C12	457:470	In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-d-galactopyranosyl)-l-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells.
35026558	1	52	theme	serine	145:150	arg1	O-glycosylation					126:140	Mucin-type O-glycosylation	115:140	Mucin-type O-glycosylation of serine or threonine residue in proteins	115:183	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	1	53	theme	post-translational	217:234	arg1	modifications					236:248	the major post-translational modifications	207:248	the major post-translational modifications	207:248	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	4	54	gly	glycosylated	800:811	arg1	products					813:820	glycosylated products	800:820	glycosylated products	800:820	The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers.
35026558	7	55	theme	acid	1437:1440	arg1	residues					1442:1449	amino acid residues	1431:1449	amino acid residues conjugated to GalNAc	1431:1470	These results indicate that glycosyltransferases involved in the biosynthesis of mucin-type O-glycans distinguish amino acid residues conjugated to GalNAc.
35026558	3	56	theme	saccharide	622:631	arg1	primers					633:639	the saccharide primers	618:639	the saccharide primers	618:639	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	6	57	theme	cell-free	1224:1232	arg1	synthesis					1234:1242	cell-free synthesis	1224:1242	cell-free synthesis	1224:1242	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	1	58	theme	modifications	236:248	arg1	modifications					236:248	the major post-translational modifications	207:248	the major post-translational modifications	207:248	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	1	58	theme	modifications	236:248	arg1	one					200:202	one	200:202	one	200:202	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	3	59	theme	enzyme	767:772	arg1	digestion					774:782	enzyme digestion	767:782	enzyme digestion	767:782	Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion.
35026558	8	60	theme	oligosaccharide	1604:1618	arg1	libraries					1620:1628	oligosaccharide libraries	1604:1628	oligosaccharide libraries	1604:1628	The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.
35026558	1	61	theme	threonine	155:163	arg1	O-glycosylation					126:140	Mucin-type O-glycosylation	115:140	Mucin-type O-glycosylation of serine or threonine residue in proteins	115:183	Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications.
35026558	0	62	theme	saccharide	49:58	arg1	primers					60:66	saccharide primers	49:66	saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues	49:112	In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
35026558	6	63	theme	acid	1266:1269	arg1	selectivity					1271:1281	the same amino acid selectivity	1251:1281	the same amino acid selectivity	1251:1281	Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments.
35026558	0	64	dep	In	0:1	arg1	vitro					3:7	vitro	3:7	vitro	3:7	In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues.
35026558	7	65	theme	O-glycans	1409:1417	arg1	biosynthesis					1382:1393	the biosynthesis	1378:1393	the biosynthesis of mucin-type O-glycans	1378:1417	These results indicate that glycosyltransferases involved in the biosynthesis of mucin-type O-glycans distinguish amino acid residues conjugated to GalNAc.
35026558	5	66	theme	in	904:905	arg1	synthesis					913:921	in vitro synthesis	904:921	in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc)	904:1023	For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue.
34631661	7	0	gly	N-glycosites	1390:1401	arg2	proteins					1423:1430	the SARS-CoV-2 S proteins	1406:1430	the SARS-CoV-2 S proteins produced in CHO and HEK	1406:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	7	0	gly	N-glycosites	1390:1401	arg1	proteins					1423:1430	the SARS-CoV-2 S proteins	1406:1430	the SARS-CoV-2 S proteins produced in CHO and HEK	1406:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	7	0	gly	N-glycosites	1390:1401	arg2	N-glycosites					1390:1401	the 22 predicted N-glycosites	1373:1401	the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK	1373:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	11	1	from	sites	2032:2036	arg1	HEK-Spike					2094:2102	HEK-Spike	2094:2102	HEK-Spike	2094:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	8	2	theme	CHO	1612:1614	arg1	cells					1624:1628	CHO and HEK cells	1612:1628	cells	1624:1628	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	1	3	theme	glycosylated	269:280	arg1	protein					292:298	the extensively glycosylated spike (S) protein	253:298	the extensively glycosylated spike (S) protein protruding from the viral envelope	253:333	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	4	4	theme	two-step	857:864	arg1	process					876:882	a two-step amidation process	855:882	a two-step amidation process	855:882	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	7	5	theme	proteins	1423:1430	arg1	proteins					1423:1430	the SARS-CoV-2 S proteins	1406:1430	the SARS-CoV-2 S proteins produced in CHO and HEK	1406:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	7	5	theme	proteins	1423:1430	arg1	N-glycosites					1390:1401	the 22 predicted N-glycosites	1373:1401	the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK	1373:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	3	6	theme	trimerization	707:719	arg1	motif					721:725	a C-terminal trimerization motif	694:725	a C-terminal trimerization motif	694:725	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	8	7	theme	HEK	1620:1622	arg1	cells					1624:1628	CHO and HEK cells	1612:1628	cells	1624:1628	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	7	8	theme	SARS-CoV-2	1410:1419	arg1	proteins					1423:1430	the SARS-CoV-2 S proteins	1406:1430	the SARS-CoV-2 S proteins produced in CHO and HEK	1406:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	9	9	dep	complex	1748:1754	arg1	α2,3-linked					1780:1790	α2,3-linked	1780:1790	α2,3-linked	1780:1790	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	13	10	theme	spike	2416:2420	arg1	proteins					2422:2429	recombinant human spike proteins	2398:2429	recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2398:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	1	11	theme	acute	184:188	arg1	virus					238:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	4	12	theme	S	844:844	arg1	protein					846:852	S protein	844:852	S protein	844:852	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	0	13	theme	Cell	156:159	arg1	Substrates					161:170	CHO and HEK Cell Substrates	144:170	Substrates	161:170	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	11	14	dep	sites	2032:2036	arg1	N1134					2084:2088	N1134	2084:2088	N1134	2084:2088	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	11	14	dep	sites	2032:2036	arg1	N709					2062:2065	N709	2062:2065	N709	2062:2065	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	11	14	dep	sites	2032:2036	arg1	N343					2050:2053	N343	2050:2053	N343	2050:2053	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	11	14	dep	sites	2032:2036	arg1	N17					2039:2041	N17	2039:2041	N17	2039:2041	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	11	14	dep	sites	2032:2036	arg1	N801					2074:2077	N801	2074:2077	N801	2074:2077	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	6	15	theme	collision	1226:1234	arg1	fragmentation					1257:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	1	16	theme	syndrome	202:209	arg1	virus					238:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	2	17	theme	human	555:559	arg1	kidney					571:576	human embryonic kidney	555:576	human embryonic kidney (HEK) cells	555:588	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	17	theme	human	555:559	arg1	HEK					579:581	HEK	579:581	HEK	579:581	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	7	18	theme	predicted	1380:1388	arg1	proteins					1423:1430	the SARS-CoV-2 S proteins	1406:1430	the SARS-CoV-2 S proteins produced in CHO and HEK	1406:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	7	18	theme	predicted	1380:1388	arg1	N-glycosites					1390:1401	the 22 predicted N-glycosites	1373:1401	the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK	1373:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	8	19	from	positions	1557:1565	arg1	absent					1595:1600	absent	1595:1600	absent	1595:1600	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	19	from	positions	1557:1565	arg1	N-glycosite					1493:1503	the N-glycosite	1489:1503	the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158)	1489:1588	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	4	20	gly	glycopeptides	1052:1064	arg1	protein					1077:1083	the S protein	1071:1083	the S protein	1071:1083	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	4	20	gly	glycopeptides	1052:1064	arg2	glycopeptides					1052:1064	glycopeptides	1052:1064	glycopeptides	1052:1064	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	4	21	theme	hydroxide	922:930	arg1	reactions					932:940	dimethylamine and ammonium hydroxide reactions	895:940	dimethylamine and ammonium hydroxide reactions	895:940	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	12	22	theme	different	2199:2207	arg1	profiles					2240:2247	different host immune system interaction profiles	2199:2247	different host immune system interaction profiles based on known immune system active lectins	2199:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	6	23	theme	electron-transfer/higher-energy	1194:1224	arg1	fragmentation					1257:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	9	24	theme	α2,3-	1866:1870	arg1	acids					1895:1899	α2,3- and α2,6-linked sialic acids	1866:1899	α2,3- and α2,6-linked sialic acids	1866:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	3	25	theme	HEK	763:765	arg1	suspensions					772:782	CHO and HEK cell suspensions	755:782	suspensions	772:782	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	6	26	theme	glycosylation	1318:1330	arg1	patterns					1332:1339	global and site-specific N-linked glycosylation patterns	1284:1339	global and site-specific N-linked glycosylation patterns	1284:1339	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	9	27	theme	S	1700:1700	arg1	proteins					1702:1709	recombinant human S proteins	1682:1709	recombinant human S proteins	1682:1709	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	4	28	from	protein	1077:1083	arg1	glycans					1040:1046	glycans	1040:1046	glycans	1040:1046	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	4	28	from	protein	1077:1083	arg1	glycopeptides					1052:1064	glycopeptides	1052:1064	glycopeptides	1052:1064	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	13	29	from	cells	2448:2452	arg1	proteins					2422:2429	recombinant human spike proteins	2398:2429	recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2398:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	13	29	from	cells	2448:2452	arg1	glycosylation					2381:2393	the site-specific glycosylation	2363:2393	the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2363:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	12	30	theme	immune	2214:2219	arg1	system					2221:2226	host immune system	2209:2226	different host immune system interaction profiles based on known immune system active lectins	2199:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	9	31	theme	α2,6-linked	1876:1886	arg1	acids					1895:1899	α2,3- and α2,6-linked sialic acids	1866:1899	α2,3- and α2,6-linked sialic acids	1866:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	3	32	theme	CHO	755:757	arg1	suspensions					772:782	CHO and HEK cell suspensions	755:782	suspensions	772:782	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	6	33	theme	site-specific	1295:1307	arg1	patterns					1332:1339	global and site-specific N-linked glycosylation patterns	1284:1339	global and site-specific N-linked glycosylation patterns	1284:1339	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	11	34	theme	abundant	2023:2030	arg1	sites					2032:2036	high-mannose abundant sites	2010:2036	high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	2010:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	9	35	link	α2,6-linked	1876:1886	arg1	acids					1895:1899	α2,3- and α2,6-linked sialic acids	1866:1899	α2,3- and α2,6-linked sialic acids	1866:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	2	36	theme	kidney	571:576	arg1	cells					584:588	human embryonic kidney (HEK) cells	555:588	human embryonic kidney (HEK) cells	555:588	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	9	37	theme	acids	1895:1899	arg1	amount					1856:1861	a small amount	1848:1861	a small amount of α2,3- and α2,6-linked sialic acids	1848:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	9	37	theme	acids	1895:1899	arg1	acids					1895:1899	α2,3- and α2,6-linked sialic acids	1866:1899	α2,3- and α2,6-linked sialic acids	1866:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	10	38	theme	abundant	1935:1942	arg1	glycosite					1944:1952	the most abundant glycosite	1926:1952	the most abundant glycosite on both spike proteins	1926:1975	The N74 site represents the most abundant glycosite on both spike proteins.
34631661	6	39	theme	global	1284:1289	arg1	patterns					1332:1339	global and site-specific N-linked glycosylation patterns	1284:1339	global and site-specific N-linked glycosylation patterns	1284:1339	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	11	40	theme	high-mannose	2010:2021	arg1	sites					2032:2036	high-mannose abundant sites	2010:2036	high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	2010:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	13	41	theme	complex	2526:2532	arg1	protein					2548:2554	this complex and important protein	2521:2554	this complex and important protein used in research, diagnostics and vaccines	2521:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	0	42	theme	Site-specific	67:79	arg1	Patterns					95:102	Different Site-specific Glycosylation Patterns	57:102	Different Site-specific Glycosylation Patterns	57:102	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	2	43	theme	production	502:511	arg1	hosts					513:517	the main recombinant S protein production hosts	471:517	the main recombinant S protein production hosts	471:517	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	43	theme	production	502:511	arg1	ovary					539:543	Chinese hamster ovary	523:543	Chinese hamster ovary (CHO)	523:549	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	9	44	theme	structural	1649:1658	arg1	mapping					1660:1666	The structural mapping	1645:1666	The structural mapping of glycans of recombinant human S proteins	1645:1709	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	10	45	theme	spike	1962:1966	arg1	proteins					1968:1975	both spike proteins	1957:1975	both spike proteins	1957:1975	The N74 site represents the most abundant glycosite on both spike proteins.
34631661	13	46	theme	important	2538:2546	arg1	protein					2548:2554	this complex and important protein	2521:2554	this complex and important protein used in research, diagnostics and vaccines	2521:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	9	47	theme	recombinant	1682:1692	arg1	proteins					1702:1709	recombinant human S proteins	1682:1709	recombinant human S proteins	1682:1709	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	0	48	theme	SARS-CoV-2	107:116	arg1	Protein					124:130	SARS-CoV-2 Spike Protein	107:130	SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates	107:170	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	1	49	theme	enzyme-related	369:382	arg1	carboxypeptidase					384:399	angiotensin-converting enzyme-related carboxypeptidase	346:399	angiotensin-converting enzyme-related carboxypeptidase (ACE2)	346:406	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	1	49	theme	enzyme-related	369:382	arg1	ACE2					402:405	ACE2	402:405	ACE2	402:405	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	13	50	from	glycosylation	2381:2393	arg1	cells					2448:2452	HEK and CHO cells	2436:2452	cells	2448:2452	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	2	51	theme	hamster	531:537	arg1	hosts					513:517	the main recombinant S protein production hosts	471:517	the main recombinant S protein production hosts	471:517	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	51	theme	hamster	531:537	arg1	CHO					546:548	CHO	546:548	CHO	546:548	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	51	theme	hamster	531:537	arg1	ovary					539:543	Chinese hamster ovary	523:543	Chinese hamster ovary (CHO)	523:549	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	13	52	dep	understand	2473:2482	arg1	to					2463:2464	to	2463:2464	to	2463:2464	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	1	53	gly	glycosylated	269:280	arg1	protein					292:298	the extensively glycosylated spike (S) protein	253:298	the extensively glycosylated spike (S) protein protruding from the viral envelope	253:333	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	4	54	theme	sialic	1012:1017	arg1	linkages					1024:1031	the sialic acid linkages	1008:1031	the sialic acid linkages on the glycans and glycopeptides from the S protein	1008:1083	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	4	55	from	linkages	1024:1031	arg1	glycans					1040:1046	glycans	1040:1046	glycans	1040:1046	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	4	55	from	linkages	1024:1031	arg1	glycopeptides					1052:1064	glycopeptides	1052:1064	glycopeptides	1052:1064	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	13	56	theme	human	2410:2414	arg1	proteins					2422:2429	recombinant human spike proteins	2398:2429	recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2398:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	0	57	theme	Sialic	19:24	arg1	Strategy					40:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	2	58	theme	S	492:492	arg1	production					502:511	recombinant S protein production	480:511	the main recombinant S protein production hosts	471:517	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	11	59	from	HEK-Spike	2094:2102	arg1	amount					2000:2005	The relatively higher amount	1978:2005	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	1978:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	11	59	from	HEK-Spike	2094:2102	arg1	sites					2032:2036	high-mannose abundant sites	2010:2036	high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	2010:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	0	60	theme	Labeling	31:38	arg1	Strategy					40:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	9	61	theme	complex	1748:1754	arg1	content					1793:1799	more complex and higher sialylation (α2,3-linked) content	1743:1799	more complex and higher sialylation (α2,3-linked) content	1743:1799	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	2	62	theme	main	475:478	arg1	hosts					513:517	the main recombinant S protein production hosts	471:517	the main recombinant S protein production hosts	471:517	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	62	theme	main	475:478	arg1	ovary					539:543	Chinese hamster ovary	523:543	Chinese hamster ovary (CHO)	523:549	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	3	63	theme	S	620:620	arg1	protein					622:628	a recombinant S protein	606:628	a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif	606:725	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	4	64	theme	acid	816:819	arg1	linkages					821:828	the sialic acid linkages	805:828	the sialic acid linkages presenting on S protein	805:852	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	13	65	theme	recombinant	2398:2408	arg1	proteins					2422:2429	recombinant human spike proteins	2398:2429	recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2398:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	1	66	theme	viral	320:324	arg1	envelope					326:333	the viral envelope	316:333	the viral envelope	316:333	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	10	67	from	glycosite	1944:1952	arg1	proteins					1968:1975	both spike proteins	1957:1975	both spike proteins	1957:1975	The N74 site represents the most abundant glycosite on both spike proteins.
34631661	9	68	theme	sialylation	1767:1777	arg1	content					1793:1799	more complex and higher sialylation (α2,3-linked) content	1743:1799	more complex and higher sialylation (α2,3-linked) content	1743:1799	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	4	69	theme	S	1075:1075	arg1	protein					1077:1083	the S protein	1071:1083	the S protein	1071:1083	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	12	70	theme	known	2258:2262	arg1	lectins					2285:2291	known immune system active lectins	2258:2291	known immune system active lectins	2258:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	3	71	dep	protein	622:628	arg1	truncated					630:638	truncated	630:638	truncated at the transmembrane domain	630:666	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	3	71	dep	protein	622:628	arg1	engineered					672:681	engineered	672:681	engineered to express a C-terminal trimerization motif	672:725	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	12	72	theme	system	2271:2276	arg1	lectins					2285:2291	known immune system active lectins	2258:2291	known immune system active lectins	2258:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	9	73	theme	glycans	1671:1677	arg1	mapping					1660:1666	The structural mapping	1645:1666	The structural mapping of glycans of recombinant human S proteins	1645:1709	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	13	74	theme	HEK	2436:2438	arg1	cells					2448:2452	HEK and CHO cells	2436:2452	cells	2448:2452	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	13	75	theme	proteins	2422:2429	arg1	glycosylation					2381:2393	the site-specific glycosylation	2363:2393	the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2363:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	13	76	theme	site-specific	2367:2379	arg1	glycosylation					2381:2393	the site-specific glycosylation	2363:2393	the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2363:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	6	77	link	N-linked	1309:1316	arg1	patterns					1332:1339	global and site-specific N-linked glycosylation patterns	1284:1339	global and site-specific N-linked glycosylation patterns	1284:1339	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	12	78	theme	interaction	2228:2238	arg1	profiles					2240:2247	different host immune system interaction profiles	2199:2247	different host immune system interaction profiles based on known immune system active lectins	2199:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	13	79	theme	CHO	2444:2446	arg1	cells					2448:2452	HEK and CHO cells	2436:2452	cells	2448:2452	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	11	80	theme	higher	1993:1998	arg1	amount					2000:2005	The relatively higher amount	1978:2005	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	1978:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	11	80	theme	higher	1993:1998	arg1	sites					2032:2036	high-mannose abundant sites	2010:2036	high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	2010:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	1	81	theme	spike	282:286	arg1	protein					292:298	the extensively glycosylated spike (S) protein	253:298	the extensively glycosylated spike (S) protein protruding from the viral envelope	253:333	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	13	82	from	impact	2488:2493	arg1	protein					2548:2554	this complex and important protein	2521:2554	this complex and important protein used in research, diagnostics and vaccines	2521:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	11	83	theme	sites	2032:2036	arg1	amount					2000:2005	The relatively higher amount	1978:2005	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	1978:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	11	83	theme	sites	2032:2036	arg1	sites					2032:2036	high-mannose abundant sites	2010:2036	high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike	2010:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	13	84	gly	glycosylation	2381:2393	arg1	proteins					2422:2429	recombinant human spike proteins	2398:2429	recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2398:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	6	85	theme	EThcD	1250:1254	arg1	fragmentation					1257:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	1	86	theme	severe	177:182	arg1	virus					238:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	7	87	theme	S	1421:1421	arg1	proteins					1423:1430	the SARS-CoV-2 S proteins	1406:1430	the SARS-CoV-2 S proteins produced in CHO and HEK	1406:1454	We identified 21 and 19 out of the 22 predicted N-glycosites of the SARS-CoV-2 S proteins produced in CHO and HEK, respectively.
34631661	3	88	theme	C-terminal	696:705	arg1	motif					721:725	a C-terminal trimerization motif	694:725	a C-terminal trimerization motif	694:725	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	6	89	theme	dissociation	1236:1247	arg1	fragmentation					1257:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	electron-transfer/higher-energy collision dissociation (EThcD) fragmentation	1194:1269	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	1	90	theme	respiratory	190:200	arg1	virus					238:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	5	91	from	aids	1138:1141	arg1	ionization					1146:1155	ionization	1146:1155	ionization	1146:1155	The process also adds a charge to Asp and Glu which aids in ionization.
34631661	9	92	theme	small	1850:1854	arg1	amount					1856:1861	a small amount	1848:1861	a small amount of α2,3- and α2,6-linked sialic acids	1848:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	9	92	theme	small	1850:1854	arg1	acids					1895:1899	α2,3- and α2,6-linked sialic acids	1866:1899	α2,3- and α2,6-linked sialic acids	1866:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	0	93	theme	CHO	144:146	arg1	Substrates					161:170	CHO and HEK Cell Substrates	144:170	Substrates	161:170	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	1	94	theme	coronavirus	211:221	arg1	virus					238:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	4	95	theme	dimethylamine	895:907	arg1	reactions					932:940	dimethylamine and ammonium hydroxide reactions	895:940	dimethylamine and ammonium hydroxide reactions	895:940	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	12	96	theme	host	2209:2212	arg1	system					2221:2226	host immune system	2209:2226	different host immune system interaction profiles based on known immune system active lectins	2199:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	0	97	theme	HEK	152:154	arg1	Substrates					161:170	CHO and HEK Cell Substrates	144:170	Substrates	161:170	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	4	98	theme	ammonium	913:920	arg1	hydroxide					922:930	ammonium hydroxide	913:930	ammonium hydroxide	913:930	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	12	99	theme	system	2221:2226	arg1	profiles					2240:2247	different host immune system interaction profiles	2199:2247	different host immune system interaction profiles based on known immune system active lectins	2199:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	3	100	theme	cell	767:770	arg1	suspensions					772:782	CHO and HEK cell suspensions	755:782	suspensions	772:782	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	6	101	theme	N-linked	1309:1316	arg1	patterns					1332:1339	global and site-specific N-linked glycosylation patterns	1284:1339	global and site-specific N-linked glycosylation patterns	1284:1339	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	1	102	theme	primary	415:421	arg1	receptor					423:430	its primary receptor to mediate host-cell entry	411:457	its primary receptor to mediate host-cell entry	411:457	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	4	103	theme	amidation	866:874	arg1	process					876:882	a two-step amidation process	855:882	a two-step amidation process	855:882	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	1	104	dep	spike	282:286	arg1	S					289:289	S	289:289	S	289:289	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	9	105	theme	sialic	1888:1893	arg1	acids					1895:1899	α2,3- and α2,6-linked sialic acids	1866:1899	α2,3- and α2,6-linked sialic acids	1866:1899	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	2	106	theme	embryonic	561:569	arg1	kidney					571:576	human embryonic kidney	555:576	human embryonic kidney (HEK) cells	555:588	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	106	theme	embryonic	561:569	arg1	HEK					579:581	HEK	579:581	HEK	579:581	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	11	107	from	amount	2000:2005	arg1	HEK-Spike					2094:2102	HEK-Spike	2094:2102	HEK-Spike	2094:2102	The relatively higher amount of high-mannose abundant sites (N17, N234, N343, N616, N709, N717, N801, and N1134) on HEK-Spike suggests that glycan-shielding may differ among the two constructs.
34631661	0	108	theme	Glycosylation	81:93	arg1	Patterns					95:102	Different Site-specific Glycosylation Patterns	57:102	Different Site-specific Glycosylation Patterns	57:102	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	1	109	theme	host-cell	443:451	arg1	entry					453:457	host-cell entry	443:457	host-cell entry	443:457	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	N282					1574:1577	N282	1574:1577	N282	1574:1577	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	N1158					1524:1528	N1158	1524:1528	N1158	1524:1528	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	N-glycosite					1493:1503	the N-glycosite	1489:1503	the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158)	1489:1588	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	position					1514:1521	1,158 position	1508:1521	1,158 position (N1158)	1508:1529	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	positions					1557:1565	122, 282 and 1,158 positions	1538:1565	positions	1557:1565	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	N1158					1583:1587	N1158	1583:1587	N1158	1583:1587	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	absent					1595:1600	absent	1595:1600	absent	1595:1600	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	110	gly	N-glycosite	1493:1503	arg2	N122					1568:1571	N122	1568:1571	N122	1568:1571	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	4	111	theme	support	953:959	arg1	system					961:966	a solid support system	945:966	a solid support system	945:966	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	12	112	theme	immune	2264:2269	arg1	lectins					2285:2291	known immune system active lectins	2258:2291	known immune system active lectins	2258:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	13	113	theme	production	2502:2511	arg1	host					2513:2516	the production host	2498:2516	the production host	2498:2516	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	2	114	theme	protein	494:500	arg1	production					502:511	recombinant S protein production	480:511	the main recombinant S protein production hosts	471:517	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	0	115	theme	Spike	118:122	arg1	Protein					124:130	SARS-CoV-2 Spike Protein	107:130	SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates	107:170	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	1	116	theme	angiotensin-converting	346:367	arg1	carboxypeptidase					384:399	angiotensin-converting enzyme-related carboxypeptidase	346:399	angiotensin-converting enzyme-related carboxypeptidase (ACE2)	346:406	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	1	116	theme	angiotensin-converting	346:367	arg1	ACE2					402:405	ACE2	402:405	ACE2	402:405	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	4	117	dep	glycans	1040:1046	arg1	the					1036:1038	the	1036:1038	the	1036:1038	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	9	118	theme	human	1694:1698	arg1	proteins					1702:1709	recombinant human S proteins	1682:1709	recombinant human S proteins	1682:1709	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	13	119	theme	host	2513:2516	arg1	impact					2488:2493	the impact	2484:2493	the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2484:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	8	120	dep	positions	1557:1565	arg1	positions					1557:1565	122, 282 and 1,158 positions	1538:1565	positions	1557:1565	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	120	dep	positions	1557:1565	arg1	N1158					1583:1587	N1158	1583:1587	N1158	1583:1587	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	120	dep	positions	1557:1565	arg1	N282					1574:1577	N282	1574:1577	N282	1574:1577	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	120	dep	positions	1557:1565	arg1	N122					1568:1571	N122	1568:1571	N122	1568:1571	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	2	121	theme	Chinese	523:529	arg1	hosts					513:517	the main recombinant S protein production hosts	471:517	the main recombinant S protein production hosts	471:517	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	121	theme	Chinese	523:529	arg1	CHO					546:548	CHO	546:548	CHO	546:548	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	2	121	theme	Chinese	523:529	arg1	ovary					539:543	Chinese hamster ovary	523:543	Chinese hamster ovary (CHO)	523:549	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	4	122	theme	solid	947:951	arg1	system					961:966	a solid support system	945:966	a solid support system	945:966	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	0	123	theme	Linkage-specific	2:17	arg1	Strategy					40:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	13	124	dep	cells	2448:2452	arg1	understand					2473:2482	understand	2473:2482	understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines	2473:2597	Collectively, these data underscore the importance of characterizing the site-specific glycosylation of recombinant human spike proteins from HEK and CHO cells in order to better understand the impact of the production host on this complex and important protein used in research, diagnostics and vaccines.
34631661	0	125	theme	Acid	26:29	arg1	Strategy					40:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy	0:47	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	4	126	theme	acid	1019:1022	arg1	linkages					1024:1031	the sialic acid linkages	1008:1031	the sialic acid linkages on the glycans and glycopeptides from the S protein	1008:1083	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	8	127	from	position	1514:1521	arg1	absent					1595:1600	absent	1595:1600	absent	1595:1600	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	127	from	position	1514:1521	arg1	N-glycosite					1493:1503	the N-glycosite	1489:1503	the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158)	1489:1588	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	2	128	theme	recombinant	480:490	arg1	production					502:511	recombinant S protein production	480:511	the main recombinant S protein production hosts	471:517	Currently, the main recombinant S protein production hosts are Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells.
34631661	8	129	theme	122	1538:1540	arg1	positions					1557:1565	122, 282 and 1,158 positions	1538:1565	positions	1557:1565	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	129	theme	122	1538:1540	arg1	N1158					1583:1587	N1158	1583:1587	N1158	1583:1587	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	129	theme	122	1538:1540	arg1	N282					1574:1577	N282	1574:1577	N282	1574:1577	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	129	theme	122	1538:1540	arg1	N122					1568:1571	N122	1568:1571	N122	1568:1571	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	3	130	theme	recombinant	608:618	arg1	protein					622:628	a recombinant S protein	606:628	a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif	606:725	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	8	131	from	cells	1624:1628	arg1	S					1605:1605	S	1605:1605	S from CHO and HEK cells	1605:1628	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	9	132	theme	proteins	1702:1709	arg1	mapping					1660:1666	The structural mapping	1645:1666	The structural mapping of glycans of recombinant human S proteins	1645:1709	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	0	133	theme	Different	57:65	arg1	Patterns					95:102	Different Site-specific Glycosylation Patterns	57:102	Different Site-specific Glycosylation Patterns	57:102	A Linkage-specific Sialic Acid Labeling Strategy Reveals Different Site-specific Glycosylation Patterns in SARS-CoV-2 Spike Protein Produced in CHO and HEK Cell Substrates.
34631661	10	134	gly	glycosite	1944:1952	arg2	glycosite					1944:1952	the most abundant glycosite	1926:1952	the most abundant glycosite on both spike proteins	1926:1975	The N74 site represents the most abundant glycosite on both spike proteins.
34631661	9	135	theme	higher	1760:1765	arg1	sialylation					1767:1777	higher sialylation	1760:1777	higher sialylation	1760:1777	The structural mapping of glycans of recombinant human S proteins reveals that CHO-Spike exhibits more complex and higher sialylation (α2,3-linked) content while HEK-Spike exhibits more high-mannose and a small amount of α2,3- and α2,6-linked sialic acids.
34631661	3	136	theme	transmembrane	647:659	arg1	domain					661:666	the transmembrane domain	643:666	the transmembrane domain	643:666	In this study, a recombinant S protein truncated at the transmembrane domain and engineered to express a C-terminal trimerization motif was transiently produced in CHO and HEK cell suspensions.
34631661	4	137	theme	sialic	809:814	arg1	linkages					821:828	the sialic acid linkages	805:828	the sialic acid linkages presenting on S protein	805:852	To further evaluate the sialic acid linkages presenting on S protein, a two-step amidation process, employing dimethylamine and ammonium hydroxide reactions in a solid support system, was developed to differentially modify the sialic acid linkages on the glycans and glycopeptides from the S protein.
34631661	8	138	theme	1,158	1551:1555	arg1	positions					1557:1565	122, 282 and 1,158 positions	1538:1565	positions	1557:1565	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	138	theme	1,158	1551:1555	arg1	N1158					1583:1587	N1158	1583:1587	N1158	1583:1587	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	138	theme	1,158	1551:1555	arg1	N282					1574:1577	N282	1574:1577	N282	1574:1577	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	8	138	theme	1,158	1551:1555	arg1	N122					1568:1571	N122	1568:1571	N122	1568:1571	It was found that the N-glycosite at 1,158 position (N1158) and at 122, 282 and 1,158 positions (N122, N282 and N1158) were absent on S from CHO and HEK cells, respectively.
34631661	6	139	used	used	1161:1164	arg2	We					1158:1159	We	1158:1159	We	1158:1159	We used MALDI-TOF and LC-MS/MS with electron-transfer/higher-energy collision dissociation (EThcD) fragmentation to determine global and site-specific N-linked glycosylation patterns.
34631661	1	140	theme	SARS-CoV-2	226:235	arg1	virus					238:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus	173:242	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus utilizes the extensively glycosylated spike (S) protein protruding from the viral envelope to bind to angiotensin-converting enzyme-related carboxypeptidase (ACE2) as its primary receptor to mediate host-cell entry.
34631661	12	141	theme	active	2278:2283	arg1	lectins					2285:2291	known immune system active lectins	2258:2291	known immune system active lectins	2258:2291	HEK-Spike can also provide different host immune system interaction profiles based on known immune system active lectins.
34631661	10	142	theme	N74	1906:1908	arg1	site					1910:1913	The N74 site	1902:1913	The N74 site	1902:1913	The N74 site represents the most abundant glycosite on both spike proteins.
32398313	9	0	dep	albicans	2262:2269	arg1	present					2280:2286	present	2280:2286	present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2280:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	6	1	theme	cell	1157:1160	arg1	death					1162:1166	macrophage cell death	1146:1166	macrophage cell death	1146:1166	However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity.
32398313	8	2	theme	mutant	1728:1733	arg1	strain					1735:1740	the alg3Δ mutant strain	1718:1740	the alg3Δ mutant strain	1718:1740	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	12	3	theme	glycosylation	2970:2982	arg1	roles					2953:2957	the roles	2949:2957	the roles of protein glycosylation in fungal pathogenesis	2949:3005	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	8	4	theme	main	1790:1793	arg1	pathway					1811:1817	a main host cell death pathway	1788:1817	a main host cell death pathway dependent on intact core N-glycans	1788:1852	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	8	4	theme	main	1790:1793	arg1	pyroptosis					1774:1783	pyroptosis	1774:1783	pyroptosis	1774:1783	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	6	5	theme	remodeling	1232:1241	arg1	capacity					1243:1250	cell wall remodeling capacity	1222:1250	cell wall remodeling capacity	1222:1250	However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity.
32398313	2	6	theme	N-glycan	291:298	arg1	structure					305:313	N-glycan core structure	291:313	N-glycan core structure	291:313	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	8	7	theme	cell	1800:1803	arg1	pathway					1811:1817	a main host cell death pathway	1788:1817	a main host cell death pathway dependent on intact core N-glycans	1788:1852	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	8	7	theme	cell	1800:1803	arg1	pyroptosis					1774:1783	pyroptosis	1774:1783	pyroptosis	1774:1783	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	9	8	theme	lipid-linked	2462:2473	arg1	assembly					2484:2491	lipid-linked N-glycan assembly	2462:2491	lipid-linked N-glycan assembly	2462:2491	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	6	9	theme	cell	1222:1225	arg1	capacity					1243:1250	cell wall remodeling capacity	1222:1250	cell wall remodeling capacity	1222:1250	However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity.
32398313	11	10	theme	critical	2816:2823	arg1	features					2825:2832	the critical features	2812:2832	the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection	2812:2927	The results clearly demonstrated the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection.
32398313	11	11	with	interaction	2877:2887	arg1	cells					2899:2903	host cells	2894:2903	host cells	2894:2903	The results clearly demonstrated the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection.
32398313	9	12	theme	other	2224:2228	arg1	yeast					2247:2251	the other human-pathogenic yeast	2220:2251	the other human-pathogenic yeast	2220:2251	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	12	theme	other	2224:2228	arg1	albicans					2262:2269	Candida albicans	2254:2269	Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2254:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	13	theme	critical	1905:1912	arg1	feature					1914:1920	a critical feature	1903:1920	a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	1903:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	2	14	from	defects	398:404	arg1	assembly					413:420	the assembly	409:420	the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER)	409:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	7	15	theme	cell	1514:1517	arg1	death					1519:1523	remarkably reduced macrophage cell death	1484:1523	remarkably reduced macrophage cell death	1484:1523	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	9	16	theme	cell	2002:2005	arg1	escape					2007:2012	host cell escape	1997:2012	host cell escape	1997:2012	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	10	17	theme	truncated	2550:2558	arg1	N-glycans					2565:2573	truncated core N-glycans	2550:2573	truncated core N-glycans	2550:2573	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	2	18	theme	mutant	361:366	arg1	strains					368:374	mutant strains	361:374	mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER)	361:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	7	19	theme	reduced	1495:1501	arg1	death					1519:1523	remarkably reduced macrophage cell death	1484:1523	remarkably reduced macrophage cell death	1484:1523	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	11	20	theme	N-glycan	2841:2848	arg1	structure					2850:2858	the N-glycan structure	2837:2858	the N-glycan structure	2837:2858	The results clearly demonstrated the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection.
32398313	9	21	theme	Candida	2254:2260	arg1	yeast					2247:2251	the other human-pathogenic yeast	2220:2251	the other human-pathogenic yeast	2220:2251	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	21	theme	Candida	2254:2260	arg1	albicans					2262:2269	Candida albicans	2254:2269	Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2254:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	12	22	theme	agents	3139:3144	arg1	development					3107:3117	the development	3103:3117	the development of novel antifungal agents	3103:3144	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	8	23	theme	core	1839:1842	arg1	N-glycans					1844:1852	intact core N-glycans	1832:1852	intact core N-glycans	1832:1852	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	1	24	theme	immunocompromised	232:248	arg1	individuals					250:260	immunocompromised individuals	232:260	immunocompromised individuals	232:260	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	1	25	theme	Cryptococcus	118:129	arg1	neoformans					131:140	Cryptococcus neoformans	118:140	Cryptococcus neoformans	118:140	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	1	25	theme	Cryptococcus	118:129	arg1	pathogen					171:178	a human-pathogenic fungal pathogen	145:178	a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals	145:260	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	10	26	theme	fatal	2762:2766	arg1	infection					2768:2776	fatal infection	2762:2776	fatal infection	2762:2776	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	12	27	theme	infection	3062:3070	arg1	mechanism					3072:3080	the glycan-based fungal infection mechanism	3038:3080	the glycan-based fungal infection mechanism	3038:3080	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	9	28	theme	neoformansIMPORTANCE	2038:2057	arg1	dissemination					2018:2030	dissemination	2018:2030	dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2018:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	5	29	theme	acidification	1101:1113	arg1	phagocytosis					1057:1068	opsonic/nonopsonic phagocytosis	1038:1068	opsonic/nonopsonic phagocytosis	1038:1068	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	5	29	theme	acidification	1101:1113	arg1	manipulation					1075:1086	manipulation	1075:1086	manipulation of phagosome acidification	1075:1113	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	5	29	theme	acidification	1101:1113	arg1	attachment					1001:1010	attachment	1001:1010	attachment to lung epithelial cells	1001:1035	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	5	30	theme	cell	956:959	arg1	interaction					961:971	host cell interaction	951:971	host cell interaction	951:971	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	2	31	theme	structure	305:313	arg1	roles					282:286	the roles	278:286	the roles of N-glycan core structure in cryptococcal pathogenicity	278:343	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	10	32	theme	cell	2607:2610	arg1	death					2612:2616	host cell death	2602:2616	host cell death	2602:2616	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	2	33	theme	core	300:303	arg1	structure					305:313	N-glycan core structure	291:313	N-glycan core structure	291:313	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	4	34	from	model	857:861	arg1	mutant					825:830	the alg3Δ mutant	815:830	the alg3Δ mutant	815:830	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	4	34	from	model	857:861	arg1	avirulent					836:844	avirulent	836:844	avirulent	836:844	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	8	35	theme	interleukin-1β	1577:1590	arg1	levels					1567:1572	secretion levels	1557:1572	secretion levels of interleukin-1β (IL-1β)	1557:1598	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	7	36	theme	mannose	1437:1443	arg1	residues					1445:1452	six and seven mannose residues	1423:1452	six and seven mannose residues	1423:1452	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	4	37	theme	moderate	736:743	arg1	defects					762:768	moderate or nondetectable defects	736:768	moderate or nondetectable defects in virulence-associated phenotypes in vitro	736:812	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	12	38	from	roles	2953:2957	arg1	pathogenesis					2994:3005	fungal pathogenesis	2987:3005	fungal pathogenesis	2987:3005	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	3	39	theme	neutral	659:665	arg1	N-glycans					667:675	truncated neutral N-glycans	649:675	truncated neutral N-glycans carrying five mannose residues as a major species	649:725	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	5	40	theme	early	935:939	arg1	stages					941:946	early stages	935:946	early stages of host cell interaction	935:971	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	12	41	theme	roles	2953:2957	arg1	delineation					2934:2944	The delineation	2930:2944	The delineation of the roles of protein glycosylation in fungal pathogenesis	2930:3005	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	9	42	theme	outer	2091:2095	arg1	dispensable					2129:2139	dispensable	2129:2139	dispensable	2129:2139	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	42	theme	outer	2091:2095	arg1	chains					2105:2110	the outer mannose chains	2087:2110	the outer mannose chains of N-glycans	2087:2123	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	4	43	theme	nondetectable	748:760	arg1	defects					762:768	moderate or nondetectable defects	736:768	moderate or nondetectable defects in virulence-associated phenotypes in vitro	736:812	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	9	44	theme	core	2312:2315	arg1	structure					2326:2334	an intact core N-glycan structure	2302:2334	an intact core N-glycan structure	2302:2334	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	0	45	theme	neoformans	76:85	arg1	Pathogenicity					46:58	the Pathogenicity	42:58	the Pathogenicity of Cryptococcus neoformans	42:85	Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.
32398313	4	46	from	avirulent	836:844	arg1	model					857:861	a mouse model	849:861	a mouse model of systemic cryptococcosis	849:888	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	9	47	link	lipid-linked	2462:2473	arg1	assembly					2484:2491	lipid-linked N-glycan assembly	2462:2491	lipid-linked N-glycan assembly	2462:2491	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	5	48	theme	lung	1015:1018	arg1	cells					1031:1035	lung epithelial cells	1015:1035	lung epithelial cells	1015:1035	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	10	49	theme	host	2602:2605	arg1	death					2612:2616	host cell death	2602:2616	host cell death	2602:2616	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	9	50	theme	N-glycans	2115:2123	arg1	dispensable					2129:2139	dispensable	2129:2139	dispensable	2129:2139	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	50	theme	N-glycans	2115:2123	arg1	chains					2105:2110	the outer mannose chains	2087:2110	the outer mannose chains of N-glycans	2087:2123	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	11	51	theme	fungal	2912:2917	arg1	infection					2919:2927	fungal infection	2912:2927	fungal infection	2912:2927	The results clearly demonstrated the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection.
32398313	12	52	theme	fungal	3055:3060	arg1	mechanism					3072:3080	the glycan-based fungal infection mechanism	3038:3080	the glycan-based fungal infection mechanism	3038:3080	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	0	53	theme	Cell	106:109	arg1	Death					111:115	Host Cell Death	101:115	Host Cell Death	101:115	Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.
32398313	2	54	from	roles	282:286	arg1	pathogenicity					331:343	cryptococcal pathogenicity	318:343	cryptococcal pathogenicity	318:343	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	0	55	theme	Cryptococcus	63:74	arg1	neoformans					76:85	Cryptococcus neoformans	63:85	Cryptococcus neoformans	63:85	Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.
32398313	2	56	theme	lipid-linked	425:436	arg1	N-glycans					438:446	lipid-linked N-glycans	425:446	lipid-linked N-glycans	425:446	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	0	57	theme	Core	0:3	arg1	Structures					14:23	Core N-Glycan Structures	0:23	Core N-Glycan Structures	0:23	Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.
32398313	2	58	theme	endoplasmic	475:485	arg1	reticulum					487:495	the endoplasmic reticulum	471:495	the endoplasmic reticulum (ER)	471:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	2	58	theme	endoplasmic	475:485	arg1	ER					498:499	ER	498:499	ER	498:499	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	8	59	theme	marrow-derived	1629:1642	arg1	cells					1654:1658	the bone marrow-derived dendritic cells	1620:1658	the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain	1620:1740	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	10	60	theme	pulmonary	2675:2683	arg1	escape					2685:2690	pulmonary escape and dissemination	2675:2708	escape	2685:2690	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	10	61	theme	neoformans	2716:2725	arg1	dissemination					2696:2708	pulmonary escape and dissemination	2675:2708	dissemination	2696:2708	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	10	61	theme	neoformans	2716:2725	arg1	escape					2685:2690	pulmonary escape and dissemination	2675:2708	escape	2685:2690	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	4	62	theme	systemic	866:873	arg1	cryptococcosis					875:888	systemic cryptococcosis	866:888	systemic cryptococcosis	866:888	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	2	63	theme	luminal	455:461	arg1	side					463:466	the luminal side	451:466	the luminal side of the endoplasmic reticulum (ER)	451:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	7	64	theme	truncated	1393:1401	arg1	N-glycans					1408:1416	truncated core N-glycans	1393:1416	truncated core N-glycans	1393:1416	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	10	65	theme	alg	2523:2525	arg1	defective					2580:2588	defective	2580:2588	defective	2580:2588	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	10	65	theme	alg	2523:2525	arg1	mutants					2532:2538	The alg null mutants	2519:2538	The alg null mutants producing truncated core N-glycans	2519:2573	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	3	66	theme	mannose	691:697	arg1	residues					699:706	five mannose residues	686:706	five mannose residues	686:706	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	3	66	theme	mannose	691:697	arg1	species					719:725	a major species	711:725	a major species	711:725	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	5	67	theme	phagosome	1091:1099	arg1	acidification					1101:1113	phagosome acidification	1091:1113	phagosome acidification	1091:1113	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	9	68	theme	cells	1950:1954	arg1	death					1936:1940	death	1936:1940	death	1936:1940	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	68	theme	cells	1950:1954	arg1	strategy					1984:1991	a strategy	1982:1991	a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	1982:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	8	69	link	marrow-derived	1629:1642	arg1	cells					1654:1658	the bone marrow-derived dendritic cells	1620:1658	the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain	1620:1740	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	5	70	theme	opsonic/nonopsonic	1038:1055	arg1	phagocytosis					1057:1068	opsonic/nonopsonic phagocytosis	1038:1068	opsonic/nonopsonic phagocytosis	1038:1068	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	1	71	theme	human-pathogenic	147:162	arg1	neoformans					131:140	Cryptococcus neoformans	118:140	Cryptococcus neoformans	118:140	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	1	71	theme	human-pathogenic	147:162	arg1	pathogen					171:178	a human-pathogenic fungal pathogen	145:178	a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals	145:260	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	3	72	theme	major	713:717	arg1	residues					699:706	five mannose residues	686:706	five mannose residues	686:706	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	3	72	theme	major	713:717	arg1	species					719:725	a major species	711:725	a major species	711:725	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	12	73	theme	protein	2962:2968	arg1	glycosylation					2970:2982	protein glycosylation	2962:2982	protein glycosylation	2962:2982	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	4	74	from	defects	762:768	arg1	phenotypes					794:803	virulence-associated phenotypes	773:803	virulence-associated phenotypes in vitro	773:812	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	9	75	theme	intact	2305:2310	arg1	structure					2326:2334	an intact core N-glycan structure	2302:2334	an intact core N-glycan structure	2302:2334	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	7	76	theme	Dol-P-Man-dependent	1303:1321	arg1	α-1,2-mannosyltransferases					1323:1348	Dol-P-Man-dependent α-1,2-mannosyltransferases	1303:1348	Dol-P-Man-dependent α-1,2-mannosyltransferases	1303:1348	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	6	77	theme	macrophage	1146:1155	arg1	death					1162:1166	macrophage cell death	1146:1166	macrophage cell death	1146:1166	However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity.
32398313	8	78	theme	alg3Δ	1722:1726	arg1	strain					1735:1740	the alg3Δ mutant strain	1718:1740	the alg3Δ mutant strain	1718:1740	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	9	79	from	defects	2451:2457	arg1	virulence					2508:2516	in vivo virulence	2500:2516	in vivo virulence	2500:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	79	from	defects	2451:2457	arg1	assembly					2484:2491	lipid-linked N-glycan assembly	2462:2491	lipid-linked N-glycan assembly	2462:2491	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	12	80	theme	antifungal	3128:3137	arg1	agents					3139:3144	novel antifungal agents	3122:3144	novel antifungal agents	3122:3144	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	6	81	theme	wall	1227:1230	arg1	capacity					1243:1250	cell wall remodeling capacity	1222:1250	cell wall remodeling capacity	1222:1250	However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity.
32398313	9	82	dep	neoformansIMPORTANCE	2038:2057	arg1	reported					2073:2080	reported	2073:2080	reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2073:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	2	83	theme	cryptococcal	318:329	arg1	pathogenicity					331:343	cryptococcal pathogenicity	318:343	cryptococcal pathogenicity	318:343	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	8	84	theme	host	1795:1798	arg1	pathway					1811:1817	a main host cell death pathway	1788:1817	a main host cell death pathway dependent on intact core N-glycans	1788:1852	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	8	84	theme	host	1795:1798	arg1	pyroptosis					1774:1783	pyroptosis	1774:1783	pyroptosis	1774:1783	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	7	85	theme	in	1529:1530	arg1	virulence					1537:1545	in vivo virulence	1529:1545	in vivo virulence	1529:1545	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	9	86	theme	host	1997:2000	arg1	escape					2007:2012	host cell escape	1997:2012	host cell escape	1997:2012	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	10	87	theme	core	2560:2563	arg1	N-glycans					2565:2573	truncated core N-glycans	2550:2573	truncated core N-glycans	2550:2573	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	9	88	theme	human-pathogenic	2230:2245	arg1	yeast					2247:2251	the other human-pathogenic yeast	2220:2251	the other human-pathogenic yeast	2220:2251	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	88	theme	human-pathogenic	2230:2245	arg1	albicans					2262:2269	Candida albicans	2254:2269	Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2254:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	89	theme	N-glycan	2475:2482	arg1	assembly					2484:2491	lipid-linked N-glycan assembly	2462:2491	lipid-linked N-glycan assembly	2462:2491	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	8	90	theme	death	1805:1809	arg1	pathway					1811:1817	a main host cell death pathway	1788:1817	a main host cell death pathway dependent on intact core N-glycans	1788:1852	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	8	90	theme	death	1805:1809	arg1	pyroptosis					1774:1783	pyroptosis	1774:1783	pyroptosis	1774:1783	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	1	91	theme	life-threatening	192:207	arg1	meningoencephalitis					209:227	life-threatening meningoencephalitis	192:227	life-threatening meningoencephalitis	192:227	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	2	92	from	assembly	413:420	arg1	side					463:466	the luminal side	451:466	the luminal side of the endoplasmic reticulum (ER)	451:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	10	93	theme	dissemination	2696:2708	arg1	mechanism					2662:2670	a mechanism	2660:2670	a mechanism of pulmonary escape and dissemination of C. neoformans	2660:2725	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	10	93	theme	dissemination	2696:2708	arg1	phagocytosis					2624:2635	phagocytosis	2624:2635	phagocytosis	2624:2635	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	3	94	theme	-dependent	581:590	arg1	α-1,3-mannosyltransferase					592:616	dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase	543:616	dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase	543:616	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	3	94	theme	-dependent	581:590	arg1	Deletion					503:510	Deletion	503:510	Deletion	503:510	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	8	95	theme	dependent	1819:1827	arg1	pathway					1811:1817	a main host cell death pathway	1788:1817	a main host cell death pathway dependent on intact core N-glycans	1788:1852	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	8	95	theme	dependent	1819:1827	arg1	pyroptosis					1774:1783	pyroptosis	1774:1783	pyroptosis	1774:1783	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	12	96	theme	novel	3122:3126	arg1	agents					3139:3144	novel antifungal agents	3122:3144	novel antifungal agents	3122:3144	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	7	97	theme	macrophage	1503:1512	arg1	death					1519:1523	remarkably reduced macrophage cell death	1484:1523	remarkably reduced macrophage cell death	1484:1523	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	11	98	theme	structure	2850:2858	arg1	features					2825:2832	the critical features	2812:2832	the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection	2812:2927	The results clearly demonstrated the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection.
32398313	12	99	theme	fungal	2987:2992	arg1	pathogenesis					2994:3005	fungal pathogenesis	2987:3005	fungal pathogenesis	2987:3005	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	9	100	theme	in	2500:2501	arg1	virulence					2508:2516	in vivo virulence	2500:2516	in vivo virulence	2500:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	8	101	theme	intact	1832:1837	arg1	N-glycans					1844:1852	intact core N-glycans	1832:1852	intact core N-glycans	1832:1852	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	8	102	theme	secretion	1557:1565	arg1	levels					1567:1572	secretion levels	1557:1572	secretion levels of interleukin-1β (IL-1β)	1557:1598	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	5	103	theme	host	951:954	arg1	interaction					961:971	host cell interaction	951:971	host cell interaction	951:971	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	5	104	attach	attachment	1001:1010	arg2	acidification					1101:1113	phagosome acidification	1091:1113	phagosome acidification	1091:1113	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	5	104	attach	attachment	1001:1010	arg1	cells					1031:1035	lung epithelial cells	1015:1035	lung epithelial cells	1015:1035	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	3	105	theme	N-glycans	667:675	arg1	production					635:644	the production	631:644	the production of truncated neutral N-glycans carrying five mannose residues as a major species	631:725	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	5	106	theme	interaction	961:971	arg1	stages					941:946	early stages	935:946	early stages of host cell interaction	935:971	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	9	107	theme	neoformans	2165:2174	arg1	virulence					2149:2157	the virulence	2145:2157	the virulence	2145:2157	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	4	108	theme	virulence-associated	773:792	arg1	phenotypes					794:803	virulence-associated phenotypes	773:803	virulence-associated phenotypes in vitro	773:812	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	7	109	theme	ALG9	1278:1281	arg1	deletion					1266:1273	deletion	1266:1273	deletion	1266:1273	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	3	110	theme	truncated	649:657	arg1	N-glycans					667:675	truncated neutral N-glycans	649:675	truncated neutral N-glycans carrying five mannose residues as a major species	649:725	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	5	111	from	defects	924:930	arg1	stages					941:946	early stages	935:946	early stages of host cell interaction	935:971	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	6	112	theme	capacity	1243:1250	arg1	loss					1214:1217	loss	1214:1217	loss of cell wall remodeling capacity	1214:1250	However, the ability to drive macrophage cell death was greatly decreased in this mutant, without loss of cell wall remodeling capacity.
32398313	7	113	dep	in	1529:1530	arg1	vivo					1532:1535	vivo	1532:1535	vivo	1532:1535	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	1	114	theme	fungal	164:169	arg1	neoformans					131:140	Cryptococcus neoformans	118:140	Cryptococcus neoformans	118:140	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	1	114	theme	fungal	164:169	arg1	pathogen					171:178	a human-pathogenic fungal pathogen	145:178	a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals	145:260	Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals.
32398313	9	115	contain	have	2446:2449	arg1	strains					2433:2439	alg3Δ, alg9Δ, and alg12Δ strains	2408:2439	alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2408:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	115	contain	have	2446:2449	arg2	defects					2451:2457	defects	2451:2457	defects in lipid-linked N-glycan assembly and in in vivo virulence	2451:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	116	theme	mannose	2097:2103	arg1	dispensable					2129:2139	dispensable	2129:2139	dispensable	2129:2139	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	116	theme	mannose	2097:2103	arg1	chains					2105:2110	the outer mannose chains	2087:2110	the outer mannose chains of N-glycans	2087:2123	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	9	117	theme	N-glycan	2317:2324	arg1	structure					2326:2334	an intact core N-glycan structure	2302:2334	an intact core N-glycan structure	2302:2334	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	0	118	theme	Host	101:104	arg1	Death					111:115	Host Cell Death	101:115	Host Cell Death	101:115	Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.
32398313	12	119	from	delineation	2934:2944	arg1	pathogenesis					2994:3005	fungal pathogenesis	2987:3005	fungal pathogenesis	2987:3005	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	7	120	dep	α-1,2-mannosyltransferases	1323:1348	arg1	generating					1382:1391	generating	1382:1391	generating	1382:1391	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	2	121	with	strains	368:374	arg1	defects					398:404	defects	398:404	defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER)	398:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	9	122	theme	N-glycan	1880:1887	arg1	structures					1889:1898	N-glycan structures	1880:1898	N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	1880:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	4	123	theme	alg3Δ	819:823	arg1	mutant					825:830	the alg3Δ mutant	815:830	the alg3Δ mutant	815:830	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	4	123	theme	alg3Δ	819:823	arg1	avirulent					836:844	avirulent	836:844	avirulent	836:844	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	5	124	theme	epithelial	1020:1029	arg1	cells					1031:1035	lung epithelial cells	1015:1035	lung epithelial cells	1015:1035	Notably, the mutant did not show defects in early stages of host cell interaction during infection, including attachment to lung epithelial cells, opsonic/nonopsonic phagocytosis, and manipulation of phagosome acidification.
32398313	2	125	theme	N-glycans	438:446	arg1	assembly					413:420	the assembly	409:420	the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER)	409:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	0	126	theme	N-Glycan	5:12	arg1	Structures					14:23	Core N-Glycan Structures	0:23	Core N-Glycan Structures	0:23	Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.
32398313	9	127	dep	in	2500:2501	arg1	vivo					2503:2506	vivo	2503:2506	vivo	2503:2506	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	2	128	theme	reticulum	487:495	arg1	side					463:466	the luminal side	451:466	the luminal side of the endoplasmic reticulum (ER)	451:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	8	129	theme	dendritic	1644:1652	arg1	cells					1654:1658	the bone marrow-derived dendritic cells	1620:1658	the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain	1620:1740	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	10	130	theme	escape	2685:2690	arg1	mechanism					2662:2670	a mechanism	2660:2670	a mechanism of pulmonary escape and dissemination of C. neoformans	2660:2725	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	10	130	theme	escape	2685:2690	arg1	phagocytosis					2624:2635	phagocytosis	2624:2635	phagocytosis	2624:2635	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	9	131	theme	neoformans	2355:2364	arg1	pathogenicity					2366:2378	C. neoformans pathogenicity	2352:2378	C. neoformans pathogenicity	2352:2378	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	7	132	theme	core	1403:1406	arg1	N-glycans					1408:1416	truncated core N-glycans	1393:1416	truncated core N-glycans	1393:1416	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32398313	2	133	link	lipid-linked	425:436	arg1	N-glycans					438:446	lipid-linked N-glycans	425:446	lipid-linked N-glycans	425:446	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	10	134	theme	null	2527:2530	arg1	defective					2580:2588	defective	2580:2588	defective	2580:2588	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	10	134	theme	null	2527:2530	arg1	mutants					2532:2538	The alg null mutants	2519:2538	The alg null mutants producing truncated core N-glycans	2519:2573	The alg null mutants producing truncated core N-glycans were defective in inducing host cell death after phagocytosis, which is triggered as a mechanism of pulmonary escape and dissemination of C. neoformans, thus becoming inactive in causing fatal infection.
32398313	8	135	theme	Asc-	1674:1677	arg1	mice					1699:1702	Asc- and Gsdmd-deficient mice	1674:1702	Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain	1674:1740	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	9	136	theme	host	1945:1948	arg1	cells					1950:1954	host cells	1945:1954	host cells	1945:1954	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	8	137	theme	Gsdmd-deficient	1683:1697	arg1	mice					1699:1702	Asc- and Gsdmd-deficient mice	1674:1702	Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain	1674:1740	However, secretion levels of interleukin-1β (IL-1β) were not reduced in the bone marrow-derived dendritic cells obtained from Asc- and Gsdmd-deficient mice infected with the alg3Δ mutant strain, excluding the possibility that pyroptosis is a main host cell death pathway dependent on intact core N-glycans.
32398313	4	138	theme	cryptococcosis	875:888	arg1	model					857:861	a mouse model	849:861	a mouse model of systemic cryptococcosis	849:888	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	12	139	from	pathogenesis	2994:3005	arg1	delineation					2934:2944	The delineation	2930:2944	The delineation of the roles of protein glycosylation in fungal pathogenesis	2930:3005	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	2	140	theme	neoformans	382:391	arg1	strains					368:374	mutant strains	361:374	mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER)	361:500	To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strains of C. neoformans with defects in the assembly of lipid-linked N-glycans in the luminal side of the endoplasmic reticulum (ER).
32398313	11	141	theme	host	2894:2897	arg1	cells					2899:2903	host cells	2894:2903	host cells	2894:2903	The results clearly demonstrated the critical features of the N-glycan structure in mediating the interaction with host cells during fungal infection.
32398313	3	142	theme	ALG3	515:518	arg1	α-1,3-mannosyltransferase					592:616	dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase	543:616	dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase	543:616	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	3	142	theme	ALG3	515:518	arg1	Deletion					503:510	Deletion	503:510	Deletion	503:510	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	12	143	theme	glycan-based	3042:3053	arg1	mechanism					3072:3080	the glycan-based fungal infection mechanism	3038:3080	the glycan-based fungal infection mechanism	3038:3080	The delineation of the roles of protein glycosylation in fungal pathogenesis not only provides insight into the glycan-based fungal infection mechanism but also will aid in the development of novel antifungal agents.
32398313	3	144	contain	carrying	677:684	arg2	species					719:725	a major species	711:725	a major species	711:725	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	3	144	contain	carrying	677:684	arg1	N-glycans					667:675	truncated neutral N-glycans	649:675	truncated neutral N-glycans carrying five mannose residues as a major species	649:725	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	3	144	contain	carrying	677:684	arg2	residues					699:706	five mannose residues	686:706	five mannose residues	686:706	Deletion of ALG3 (alg3Δ), which encodes dolichyl-phosphate-mannose (Dol-P-Man)-dependent α-1,3-mannosyltransferase, resulted in the production of truncated neutral N-glycans carrying five mannose residues as a major species.
32398313	9	145	theme	stark	2189:2193	arg1	contrast					2195:2202	stark contrast	2189:2202	stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence	2189:2516	Our results demonstrated N-glycan structures as a critical feature in modulating death of host cells, which is exploited by as a strategy for host cell escape for dissemination of C. neoformansIMPORTANCE We previously reported that the outer mannose chains of N-glycans are dispensable for the virulence of C. neoformans, which is in stark contrast to findings for the other human-pathogenic yeast, Candida albicans Here, we present evidence that an intact core N-glycan structure is required for C. neoformans pathogenicity by systematically analyzing alg3Δ, alg9Δ, and alg12Δ strains that have defects in lipid-linked N-glycan assembly and in in vivo virulence.
32398313	4	146	theme	mouse	851:855	arg1	model					857:861	a mouse model	849:861	a mouse model of systemic cryptococcosis	849:888	Despite moderate or nondetectable defects in virulence-associated phenotypes in vitro, the alg3Δ mutant was avirulent in a mouse model of systemic cryptococcosis.
32398313	7	147	theme	ALG12	1287:1291	arg1	deletion					1266:1273	deletion	1266:1273	deletion	1266:1273	Furthermore, deletion of ALG9 and ALG12, encoding Dol-P-Man-dependent α-1,2-mannosyltransferases and α-1,6-mannosyltransferases, generating truncated core N-glycans with six and seven mannose residues, respectively, also displayed remarkably reduced macrophage cell death and in vivo virulence.
32915505	0	0	from	Characterization	11:26	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	0	from	Characterization	11:26	arg1	Domain					72:77	the Receptor Binding Domain	51:77	the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	51:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	1	1	theme	glycan	158:163	arg1	structures					165:174	The glycan structures	154:174	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	154:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	1	2	theme	human	256:260	arg1	cells					270:274	human HEK293F cells	256:274	human HEK293F cells	256:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	0	3	theme	Spike	97:101	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	5	4	theme	view	959:962	arg1	point					950:954	the lectin's point	937:954	the lectin's point of view	937:962	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	6	5	theme	3D	1067:1068	arg1	models					1070:1075	3D models	1067:1075	3D models of the interacting complexes	1067:1104	Based on these findings, 3D models of the interacting complexes have been proposed.
32915505	1	6	theme	HEK293F	262:268	arg1	cells					270:274	human HEK293F cells	256:274	human HEK293F cells	256:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	0	7	theme	SARS-CoV-2	86:95	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	4	8	theme	C-type	819:824	arg1	lectins					826:832	C-type lectins	819:832	C-type lectins (DC-SIGN, MGL)	819:847	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	2	9	located	found	457:461	arg1	analyses					484:491	previous MS-based analyses	466:491	previous MS-based analyses	466:491	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	2	9	located	found	457:461	arg2	structures					442:451	glycan structures	435:451	glycan structures not found in previous MS-based analyses	435:491	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	3	10	theme	different	548:556	arg1	lectins					564:570	different human lectins	548:570	different human lectins	548:570	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	6	11	theme	interacting	1084:1094	arg1	complexes					1096:1104	the interacting complexes	1080:1104	the interacting complexes	1080:1104	Based on these findings, 3D models of the interacting complexes have been proposed.
32915505	1	12	gly	glycoprotein	230:241	arg1	glycoprotein					230:241	the SARS-CoV2 spike glycoprotein	210:241	the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	210:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	3	13	theme	C-labelled	524:533	arg1	glycans					535:541	the RBD 13 C-labelled glycans	513:541	the RBD 13 C-labelled glycans	513:541	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	0	14	theme	Protein	103:109	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	14	theme	Protein	103:109	arg1	Domain					72:77	the Receptor Binding Domain	51:77	the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	51:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	4	15	dep	lectins	826:832	arg1	MGL					844:846	MGL	844:846	MGL	844:846	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	4	15	dep	lectins	826:832	arg1	DC-SIGN					835:841	DC-SIGN	835:841	DC-SIGN	835:841	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	2	16	theme	structures	442:451	arg1	presence					423:430	the presence	419:430	the presence of glycan structures not found in previous MS-based analyses	419:491	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	0	17	from	Glycans	40:46	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	17	from	Glycans	40:46	arg1	Domain					72:77	the Receptor Binding Domain	51:77	the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	51:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	18	theme	Structural	0:9	arg1	Characterization					11:26	Structural Characterization	0:26	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	0:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	3	19	with	interaction	498:508	arg1	lectins					564:570	different human lectins	548:570	different human lectins	548:570	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	5	20	theme	Complementary	869:881	arg1	experiments					883:893	Complementary experiments	869:893	Complementary experiments from the glycoprotein perspective or from the lectin's point of view	869:962	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	1	21	theme	receptor	183:190	arg1	glycoprotein					230:241	the SARS-CoV2 spike glycoprotein	210:241	the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	210:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	1	21	theme	receptor	183:190	arg1	domain					200:205	the receptor binding domain	179:205	the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	179:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	0	22	theme	N-Linked	31:38	arg1	Glycans					40:46	N-Linked Glycans	31:46	N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	31:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	3	23	theme	human	558:562	arg1	lectins					564:570	different human lectins	548:570	different human lectins	548:570	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	1	24	theme	binding	192:198	arg1	glycoprotein					230:241	the SARS-CoV2 spike glycoprotein	210:241	the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	210:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	1	24	theme	binding	192:198	arg1	domain					200:205	the receptor binding domain	179:205	the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	179:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	6	25	theme	complexes	1096:1104	arg1	models					1070:1075	3D models	1067:1075	3D models of the interacting complexes	1067:1104	Based on these findings, 3D models of the interacting complexes have been proposed.
32915505	5	26	theme	specific	998:1005	arg1	epitopes					1019:1026	the specific interacting epitopes	994:1026	the specific interacting epitopes in each case	994:1039	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	4	27	dep	galectins	737:745	arg1	-7					761:762	-7	761:762	-7	761:762	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	4	27	dep	galectins	737:745	arg1	N-terminal					771:780	N-terminal	771:780	N-terminal	771:780	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	4	27	dep	galectins	737:745	arg1	galectins-3					748:758	galectins-3	748:758	galectins-3	748:758	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	5	28	from	point	950:954	arg1	experiments					883:893	Complementary experiments	869:893	Complementary experiments from the glycoprotein perspective or from the lectin's point of view	869:962	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	1	29	theme	domain	200:205	arg1	structures					165:174	The glycan structures	154:174	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	154:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	2	30	theme	MS-based	475:482	arg1	analyses					484:491	previous MS-based analyses	466:491	previous MS-based analyses	466:491	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	0	31	theme	Human	139:143	arg1	Lectins					145:151	Human Lectins	139:151	Human Lectins	139:151	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	5	32	theme	interacting	1007:1017	arg1	epitopes					1019:1026	the specific interacting epitopes	994:1026	the specific interacting epitopes in each case	994:1039	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	0	33	theme	Glycans	40:46	arg1	Characterization					11:26	Structural Characterization	0:26	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	0:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	33	theme	Glycans	40:46	arg1	Interactions					121:132	their Interactions	115:132	their Interactions with Human Lectins	115:151	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	2	34	theme	previous	466:473	arg1	analyses					484:491	previous MS-based analyses	466:491	previous MS-based analyses	466:491	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	0	35	from	Domain	72:77	arg1	Characterization					11:26	Structural Characterization	0:26	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	0:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	35	from	Domain	72:77	arg1	Interactions					121:132	their Interactions	115:132	their Interactions with Human Lectins	115:151	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	1	36	theme	glycoprotein	230:241	arg1	glycoprotein					230:241	the SARS-CoV2 spike glycoprotein	210:241	the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	210:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	1	36	theme	glycoprotein	230:241	arg1	domain					200:205	the receptor binding domain	179:205	the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	179:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	0	37	theme	Receptor	55:62	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	37	theme	Receptor	55:62	arg1	Domain					72:77	the Receptor Binding Domain	51:77	the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	51:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	5	38	from	epitopes	1019:1026	arg1	case					1036:1039	each case	1031:1039	each case	1031:1039	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	5	39	theme	glycoprotein	904:915	arg1	perspective					917:927	the glycoprotein perspective	900:927	the glycoprotein perspective	900:927	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	2	40	theme	glycan	435:440	arg1	structures					442:451	glycan structures	435:451	glycan structures not found in previous MS-based analyses	435:491	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	4	41	dep	Siglecs	784:790	arg1	Siglec-10					803:811	Siglec-10	803:811	Siglec-10	803:811	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	4	41	dep	Siglecs	784:790	arg1	Siglec-8					793:800	Siglec-8	793:800	Siglec-8	793:800	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	0	42	with	Characterization	11:26	arg1	Lectins					145:151	Human Lectins	139:151	Human Lectins	139:151	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	2	43	theme	interacting	331:341	arg1	epitopes					343:350	The different possible interacting epitopes	308:350	The different possible interacting epitopes	308:350	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	3	44	theme	different	596:604	arg1	organs					606:611	different organs	596:611	different organs	596:611	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	2	45	theme	possible	322:329	arg1	epitopes					343:350	The different possible interacting epitopes	308:350	The different possible interacting epitopes	308:350	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	4	46	theme	N-labelled	726:735	arg1	galectins					737:745	15 N-labelled galectins	723:745	15 N-labelled galectins (galectins-3, -7 and -8 N-terminal)	723:781	In particular, 15 N-labelled galectins (galectins-3, -7 and -8 N-terminal), Siglecs (Siglec-8, Siglec-10), and C-type lectins (DC-SIGN, MGL) have been employed.
32915505	1	47	theme	SARS-CoV2	214:222	arg1	glycoprotein					230:241	the SARS-CoV2 spike glycoprotein	210:241	the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	210:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	3	48	theme	glycans	535:541	arg1	interaction					498:508	The interaction	494:508	The interaction	494:508	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	2	49	theme	different	312:320	arg1	epitopes					343:350	The different possible interacting epitopes	308:350	The different possible interacting epitopes	308:350	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	0	50	with	Interactions	121:132	arg1	Lectins					145:151	Human Lectins	139:151	Human Lectins	139:151	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	1	51	theme	spike	224:228	arg1	glycoprotein					230:241	the SARS-CoV2 spike glycoprotein	210:241	the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells	210:274	The glycan structures of the receptor binding domain of the SARS-CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR.
32915505	5	52	gly	glycoprotein	904:915	arg1	glycoprotein					904:915	the glycoprotein perspective	900:927	the glycoprotein perspective	900:927	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
32915505	3	53	theme	infection	657:665	arg1	process					667:673	the infection process	653:673	the infection process	653:673	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	2	54	theme	presence	423:430	arg1	evidence					407:414	evidence	407:414	evidence of the presence of glycan structures not found in previous MS-based analyses	407:491	The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS-based analyses.
32915505	3	55	theme	RBD	517:519	arg1	glycans					535:541	the RBD 13 C-labelled glycans	513:541	the RBD 13 C-labelled glycans	513:541	The interaction of the RBD 13 C-labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR.
32915505	0	56	from	Interactions	121:132	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	56	from	Interactions	121:132	arg1	Domain					72:77	the Receptor Binding Domain	51:77	the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	51:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	57	theme	Binding	64:70	arg1	Protein					103:109	the SARS-CoV-2 Spike Protein	82:109	the SARS-CoV-2 Spike Protein	82:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	0	57	theme	Binding	64:70	arg1	Domain					72:77	the Receptor Binding Domain	51:77	the Receptor Binding Domain of the SARS-CoV-2 Spike Protein	51:109	Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
32915505	5	58	from	perspective	917:927	arg1	experiments					883:893	Complementary experiments	869:893	Complementary experiments from the glycoprotein perspective or from the lectin's point of view	869:962	Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case.
34128680	7	0	theme	fibrillization	1504:1517	arg1	rate					1519:1522	the fibrillization rate	1500:1522	the fibrillization rate of either peptide	1500:1540	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	8	1	theme	located	1698:1704	arg1	moiety					1691:1696	a glycan moiety	1682:1696	a glycan moiety located external to the β-sheet fibrillizing domain	1682:1748	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	5	2	theme	nonfibrillar	1215:1226	arg1	aggregates					1228:1237	nonfibrillar aggregates	1215:1237	nonfibrillar aggregates	1215:1237	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	4	3	theme	peptide	920:926	arg1	pathway					884:890	the self-assembly pathway	866:890	the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11)	866:951	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	6	4	theme	Acidic	1281:1286	arg1	buffer					1298:1303	Acidic phosphate buffer	1281:1303	Acidic phosphate buffer	1281:1303	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	8	5	theme	β-sheet	1722:1728	arg1	domain					1743:1748	the β-sheet fibrillizing domain	1718:1748	the β-sheet fibrillizing domain	1718:1748	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	1	6	used	used	289:292	arg2	peptides					193:200	short synthetic peptides	177:200	short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers)	177:276	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	4	7	theme	electron	704:711	arg1	microscopy					713:722	transmission electron microscopy	691:722	transmission electron microscopy	691:722	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	1	8	theme	elongated	226:234	arg1	nanofibers					266:275	peptide nanofibers	258:275	peptide nanofibers	258:275	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	1	8	theme	elongated	226:234	arg1	fibers					244:249	elongated β-sheet fibers	226:249	elongated β-sheet fibers (i.e., peptide nanofibers)	226:276	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	9	9	from	self-assembly	2000:2012	arg1	understanding					1944:1956	the understanding	1940:1956	the understanding of the effect of glycosylation on peptide self-assembly	1940:2012	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	4	10	gly	glycosylation	794:806	arg1	site					813:816	a site	811:816	a site external to the fibrillization domain	811:854	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	4	10	gly	glycosylation	794:806	arg2	site					813:816	a site	811:816	a site external to the fibrillization domain	811:854	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	3	11	theme	peptides	669:676	arg1	fibrillization					627:640	the fibrillization	623:640	the fibrillization of natural amyloid-forming peptides	623:676	Recent reports have shown that glycosylation can disrupt the fibrillization of natural amyloid-forming peptides.
34128680	8	12	theme	pH-dependent	1764:1775	arg1	pathway					1791:1797	the pH-dependent self-assembly pathway	1760:1797	the pH-dependent self-assembly pathway of a synthetic peptide	1760:1820	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	6	13	theme	fibrillization	1329:1342	arg1	rate					1316:1319	the rate	1312:1319	the rate of GQ11 fibrillization	1312:1342	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	3	14	theme	natural	645:651	arg1	peptides					669:676	natural amyloid-forming peptides	645:676	natural amyloid-forming peptides	645:676	Recent reports have shown that glycosylation can disrupt the fibrillization of natural amyloid-forming peptides.
34128680	7	15	theme	fibrillization	1607:1620	arg1	rate					1599:1602	the rate	1595:1602	the rate of fibrillization of both peptides	1595:1637	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	7	16	contain	had	1483:1485	arg1	strength					1474:1481	The buffer ionic strength	1457:1481	The buffer ionic strength	1457:1481	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	7	16	contain	had	1483:1485	arg2	effect					1490:1495	no effect	1487:1495	no effect	1487:1495	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	2	17	theme	carbohydrate-modified	534:554	arg1	proteins					556:563	natural carbohydrate-modified proteins	526:563	natural carbohydrate-modified proteins	526:563	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	4	18	theme	T	765:765	arg1	spectroscopy					767:778	thioflavin T spectroscopy	754:778	thioflavin T spectroscopy	754:778	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	1	19	theme	biotechnology	341:353	arg1	applications					355:366	diverse medical and biotechnology applications	321:366	diverse medical and biotechnology applications	321:366	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	8	20	theme	peptide	1814:1820	arg1	pathway					1791:1797	the pH-dependent self-assembly pathway	1760:1797	the pH-dependent self-assembly pathway of a synthetic peptide	1760:1820	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	9	21	gly	glycosylation	1975:1987	arg1	peptide					1992:1998	peptide self-assembly	1992:2012	peptide self-assembly	1992:2012	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	1	22	theme	short	177:181	arg1	peptides					193:200	short synthetic peptides	177:200	short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers)	177:276	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	7	23	theme	similar	1577:1583	arg1	effect					1585:1590	a similar effect	1575:1590	a similar effect	1575:1590	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	9	24	theme	future	2031:2036	arg1	efforts					2038:2044	future efforts	2031:2044	future efforts	2031:2044	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	0	25	theme	β-Sheet	93:99	arg1	Peptide					114:120	a Synthetic β-Sheet Fibrillizing Peptide	81:120	a Synthetic β-Sheet Fibrillizing Peptide	81:120	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	8	26	theme	significant	1834:1844	arg1	changes					1846:1852	significant changes	1834:1852	significant changes in the fibril mass and morphology of the structures formed	1834:1911	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	5	27	theme	N-linked	998:1005	arg1	N-acetylglucosamine					1007:1025	N-linked N-acetylglucosamine	998:1025	N-linked N-acetylglucosamine	998:1025	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	0	28	theme	Peptide	114:120	arg1	Pathway					70:76	the Self-Assembly Pathway	52:76	the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide	52:120	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	2	29	theme	protein	402:408	arg1	modification					429:440	a common protein post-translational modification	393:440	a common protein post-translational modification	393:440	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	2	29	theme	protein	402:408	arg1	Glycosylation					369:381	Glycosylation	369:381	Glycosylation	369:381	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	8	30	theme	fibril	1861:1866	arg1	mass					1868:1871	fibril mass	1861:1871	fibril mass	1861:1871	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	8	31	theme	structures	1895:1904	arg1	morphology					1877:1886	morphology	1877:1886	morphology	1877:1886	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	8	31	theme	structures	1895:1904	arg1	mass					1868:1871	fibril mass	1861:1871	fibril mass	1861:1871	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	9	32	gly	glycopeptides	2106:2118	arg2	glycopeptides					2106:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	9	33	theme	synthetic	2075:2083	arg1	glycopeptides					2106:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	4	34	theme	external	818:825	arg1	site					813:816	a site	811:816	a site external to the fibrillization domain	811:854	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	0	35	gly	Glycosylation	0:12	arg1	Appendage					35:43	a Nonfibrillizing Appendage	17:43	a Nonfibrillizing Appendage	17:43	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	5	36	theme	short	1197:1201	arg1	fibrils					1203:1209	short fibrils	1197:1209	short fibrils	1197:1209	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	9	37	theme	fibrillizing	2093:2104	arg1	glycopeptides					2106:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	0	38	theme	Appendage	35:43	arg1	Glycosylation					0:12	Glycosylation	0:12	Glycosylation of a Nonfibrillizing Appendage	0:43	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	5	39	theme	GQ11	1167:1170	arg1	tendency					1155:1162	the tendency	1151:1162	the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers	1151:1278	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	4	40	theme	synthetic	897:905	arg1	NSGSGQQKFQFQFEQQ					929:944	NSGSGQQKFQFQFEQQ	929:944	NSGSGQQKFQFQFEQQ (NQ11)	929:951	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	4	40	theme	synthetic	897:905	arg1	peptide					920:926	a synthetic fibrillizing peptide	895:926	a synthetic fibrillizing peptide	895:926	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	6	41	theme	NQ11	1417:1420	arg1	rate					1437:1440	NQ11 fibrillization rate	1417:1440	NQ11 fibrillization rate	1417:1440	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	1	42	theme	medical	329:335	arg1	applications					355:366	diverse medical and biotechnology applications	321:366	diverse medical and biotechnology applications	321:366	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	5	43	link	N-linked	998:1005	arg1	N-acetylglucosamine					1007:1025	N-linked N-acetylglucosamine	998:1025	N-linked N-acetylglucosamine	998:1025	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	4	44	theme	self-assembly	870:882	arg1	pathway					884:890	the self-assembly pathway	866:890	the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11)	866:951	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	3	45	theme	Recent	566:571	arg1	reports					573:579	Recent reports	566:579	Recent reports	566:579	Recent reports have shown that glycosylation can disrupt the fibrillization of natural amyloid-forming peptides.
34128680	0	46	theme	Self-Assembly	56:68	arg1	Pathway					70:76	the Self-Assembly Pathway	52:76	the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide	52:120	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	5	47	theme	aggregates	1228:1237	arg1	combination					1182:1192	a combination	1180:1192	a combination of short fibrils and nonfibrillar aggregates	1180:1237	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	7	48	theme	buffer	1461:1466	arg1	strength					1474:1481	The buffer ionic strength	1457:1481	The buffer ionic strength	1457:1481	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	6	49	theme	phosphate	1288:1296	arg1	buffer					1298:1303	Acidic phosphate buffer	1281:1303	Acidic phosphate buffer	1281:1303	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	1	50	theme	synthetic	183:191	arg1	peptides					193:200	short synthetic peptides	177:200	short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers)	177:276	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	7	51	theme	ionic	1468:1472	arg1	strength					1474:1481	The buffer ionic strength	1457:1481	The buffer ionic strength	1457:1481	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	4	52	theme	fibrillizing	907:918	arg1	NSGSGQQKFQFQFEQQ					929:944	NSGSGQQKFQFQFEQQ	929:944	NSGSGQQKFQFQFEQQ (NQ11)	929:951	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	4	52	theme	fibrillizing	907:918	arg1	peptide					920:926	a synthetic fibrillizing peptide	895:926	a synthetic fibrillizing peptide	895:926	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	4	53	theme	fluorescence	725:736	arg1	microscopy					738:747	fluorescence microscopy	725:747	fluorescence microscopy	725:747	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	8	54	theme	fibrillizing	1730:1741	arg1	domain					1743:1748	the β-sheet fibrillizing domain	1718:1748	the β-sheet fibrillizing domain	1718:1748	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	7	55	theme	peptides	1630:1637	arg1	fibrillization					1607:1620	fibrillization	1607:1620	fibrillization of both peptides	1607:1637	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	5	56	theme	NQ11	971:974	arg1	GlcNAc					1030:1035	N(GlcNAc)SGSG-Q11	1028:1044	N(GlcNAc)SGSG-Q11 (GQ11)	1028:1051	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	5	56	theme	NQ11	971:974	arg1	variant					976:982	an NQ11 variant	968:982	an NQ11 variant modified with N-linked N-acetylglucosamine	968:1025	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	4	57	theme	transmission	691:702	arg1	microscopy					713:722	transmission electron microscopy	691:722	transmission electron microscopy	691:722	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	3	58	theme	amyloid-forming	653:667	arg1	peptides					669:676	natural amyloid-forming peptides	645:676	natural amyloid-forming peptides	645:676	Recent reports have shown that glycosylation can disrupt the fibrillization of natural amyloid-forming peptides.
34128680	1	59	theme	β-sheet	236:242	arg1	nanofibers					266:275	peptide nanofibers	258:275	peptide nanofibers	258:275	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	1	59	theme	β-sheet	236:242	arg1	fibers					244:249	elongated β-sheet fibers	226:249	elongated β-sheet fibers (i.e., peptide nanofibers)	226:276	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	9	60	theme	effect	1965:1970	arg1	understanding					1944:1956	the understanding	1940:1956	the understanding of the effect of glycosylation on peptide self-assembly	1940:2012	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	9	61	from	glycopeptides	2106:2118	arg1	biomaterials					2057:2068	biomaterials	2057:2068	biomaterials from synthetic β-sheet fibrillizing glycopeptides	2057:2118	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	9	62	from	understanding	1944:1956	arg1	self-assembly					2000:2012	peptide self-assembly	1992:2012	peptide self-assembly	1992:2012	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	9	63	theme	glycosylation	1975:1987	arg1	effect					1965:1970	the effect	1961:1970	the effect of glycosylation on peptide self-assembly	1961:2012	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	8	64	theme	self-assembly	1777:1789	arg1	pathway					1791:1797	the pH-dependent self-assembly pathway	1760:1797	the pH-dependent self-assembly pathway of a synthetic peptide	1760:1820	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	1	65	dep	nanofibers	266:275	arg1	i.e.					252:255	i.e.	252:255	i.e.	252:255	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	9	66	theme	peptide	1992:1998	arg1	self-assembly					2000:2012	peptide self-assembly	1992:2012	peptide self-assembly	1992:2012	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	5	67	theme	deionized	1105:1113	arg1	pH					1122:1123	pH 5.8	1122:1127	pH 5.8	1122:1127	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	5	67	theme	deionized	1105:1113	arg1	water					1115:1119	deionized water	1105:1119	deionized water (pH 5.8)	1105:1128	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	2	68	theme	natural	526:532	arg1	proteins					556:563	natural carbohydrate-modified proteins	526:563	natural carbohydrate-modified proteins	526:563	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	4	69	theme	thioflavin	754:763	arg1	spectroscopy					767:778	thioflavin T spectroscopy	754:778	thioflavin T spectroscopy	754:778	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	0	70	theme	Synthetic	83:91	arg1	Peptide					114:120	a Synthetic β-Sheet Fibrillizing Peptide	81:120	a Synthetic β-Sheet Fibrillizing Peptide	81:120	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	6	71	dep	structures	1378:1387	arg1	formed					1389:1394	formed	1389:1394	formed	1389:1394	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	6	71	dep	structures	1378:1387	arg1	had					1400:1402	had	1400:1402	had no effect on NQ11 fibrillization rate or morphology	1400:1454	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	8	72	theme	synthetic	1804:1812	arg1	peptide					1814:1820	a synthetic peptide	1802:1820	a synthetic peptide	1802:1820	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	8	73	from	changes	1846:1852	arg1	morphology					1877:1886	morphology	1877:1886	morphology	1877:1886	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	8	73	from	changes	1846:1852	arg1	mass					1868:1871	fibril mass	1861:1871	fibril mass	1861:1871	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	0	74	theme	Fibrillizing	101:112	arg1	Peptide					114:120	a Synthetic β-Sheet Fibrillizing Peptide	81:120	a Synthetic β-Sheet Fibrillizing Peptide	81:120	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	6	75	theme	structures	1378:1387	arg1	morphology					1360:1369	the morphology	1356:1369	the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology	1356:1454	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	2	76	theme	proteins	556:563	arg1	function					514:521	the function	510:521	the function of natural carbohydrate-modified proteins	510:563	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	4	77	theme	fibrillization	834:847	arg1	domain					849:854	the fibrillization domain	830:854	the fibrillization domain	830:854	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	2	78	theme	post-translational	410:427	arg1	modification					429:440	a common protein post-translational modification	393:440	a common protein post-translational modification	393:440	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	2	78	theme	post-translational	410:427	arg1	Glycosylation					369:381	Glycosylation	369:381	Glycosylation	369:381	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	4	79	from	site	813:816	arg1	glycosylation					794:806	glycosylation	794:806	glycosylation at a site external to the fibrillization domain	794:854	Here, using transmission electron microscopy, fluorescence microscopy, and thioflavin T spectroscopy, we show that glycosylation at a site external to the fibrillization domain can alter the self-assembly pathway of a synthetic fibrillizing peptide, NSGSGQQKFQFQFEQQ (NQ11).
34128680	2	80	theme	peptide	476:482	arg1	nanofibers					484:493	peptide nanofibers	476:493	peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins	476:563	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	2	81	theme	common	395:400	arg1	modification					429:440	a common protein post-translational modification	393:440	a common protein post-translational modification	393:440	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	2	81	theme	common	395:400	arg1	Glycosylation					369:381	Glycosylation	369:381	Glycosylation	369:381	Glycosylation, which is a common protein post-translational modification, is gaining interest for creating peptide nanofibers that can mimic the function of natural carbohydrate-modified proteins.
34128680	0	82	theme	Nonfibrillizing	19:33	arg1	Appendage					35:43	a Nonfibrillizing Appendage	17:43	a Nonfibrillizing Appendage	17:43	Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide.
34128680	5	83	theme	N	1028:1028	arg1	GQ11					1047:1050	GQ11	1047:1050	GQ11	1047:1050	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	5	83	theme	N	1028:1028	arg1	variant					976:982	an NQ11 variant	968:982	an NQ11 variant modified with N-linked N-acetylglucosamine	968:1025	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	5	83	theme	N	1028:1028	arg1	GlcNAc					1030:1035	N(GlcNAc)SGSG-Q11	1028:1044	N(GlcNAc)SGSG-Q11 (GQ11)	1028:1051	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	9	84	theme	β-sheet	2085:2091	arg1	glycopeptides					2106:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	synthetic β-sheet fibrillizing glycopeptides	2075:2118	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	5	85	theme	fibrils	1203:1209	arg1	combination					1182:1192	a combination	1180:1192	a combination of short fibrils and nonfibrillar aggregates	1180:1237	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	7	86	theme	diphosphate	1553:1563	arg1	anion					1565:1569	the diphosphate anion	1549:1569	the diphosphate anion	1549:1569	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	5	87	theme	β-sheet	1061:1067	arg1	nanofibers					1069:1078	β-sheet nanofibers	1061:1078	β-sheet nanofibers	1061:1078	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34128680	9	88	from	effect	1965:1970	arg1	self-assembly					2000:2012	peptide self-assembly	1992:2012	peptide self-assembly	1992:2012	These observations add to the understanding of the effect of glycosylation on peptide self-assembly and should guide future efforts to develop biomaterials from synthetic β-sheet fibrillizing glycopeptides.
34128680	6	89	theme	fibrillization	1422:1435	arg1	rate					1437:1440	NQ11 fibrillization rate	1417:1440	NQ11 fibrillization rate	1417:1440	Acidic phosphate buffer slowed the rate of GQ11 fibrillization and altered the morphology of the structures formed yet had no effect on NQ11 fibrillization rate or morphology.
34128680	1	90	theme	diverse	321:327	arg1	applications					355:366	diverse medical and biotechnology applications	321:366	diverse medical and biotechnology applications	321:366	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	7	91	contain	had	1571:1573	arg1	anion					1565:1569	the diphosphate anion	1549:1569	the diphosphate anion	1549:1569	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	7	91	contain	had	1571:1573	arg2	effect					1585:1590	a similar effect	1575:1590	a similar effect	1575:1590	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	7	92	theme	peptide	1534:1540	arg1	rate					1519:1522	the fibrillization rate	1500:1522	the fibrillization rate of either peptide	1500:1540	The buffer ionic strength had no effect on the fibrillization rate of either peptide, while the diphosphate anion had a similar effect on the rate of fibrillization of both peptides.
34128680	1	93	theme	peptide	258:264	arg1	nanofibers					266:275	peptide nanofibers	258:275	peptide nanofibers	258:275	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	1	93	theme	peptide	258:264	arg1	fibers					244:249	elongated β-sheet fibers	226:249	elongated β-sheet fibers (i.e., peptide nanofibers)	226:276	Owing to their biocompatibility and biodegradability, short synthetic peptides that self-assemble into elongated β-sheet fibers (i.e., peptide nanofibers) are widely used to create biomaterials for diverse medical and biotechnology applications.
34128680	8	94	theme	glycan	1684:1689	arg1	moiety					1691:1696	a glycan moiety	1682:1696	a glycan moiety located external to the β-sheet fibrillizing domain	1682:1748	Collectively, these data demonstrate that a glycan moiety located external to the β-sheet fibrillizing domain can alter the pH-dependent self-assembly pathway of a synthetic peptide, leading to significant changes in the fibril mass and morphology of the structures formed.
34128680	5	95	theme	extended	1260:1267	arg1	nanofibers					1269:1278	extended nanofibers	1260:1278	extended nanofibers	1260:1278	Specifically, an NQ11 variant modified with N-linked N-acetylglucosamine, N(GlcNAc)SGSG-Q11 (GQ11), formed β-sheet nanofibers more slowly than NQ11 in deionized water (pH 5.8), which correlated to the tendency of GQ11 to form a combination of short fibrils and nonfibrillar aggregates, whereas NQ11 formed extended nanofibers.
34192302	6	0	theme	sample	810:815	arg1	types					817:821	five sample types	805:821	five sample types	805:821	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	3	1	theme	M2BP	497:500	arg1	marker					465:470	a novel diagnostic marker	446:470	a novel diagnostic marker	446:470	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	3	1	theme	M2BP	497:500	arg1	isomer					487:492	glycosylation isomer	473:492	glycosylation isomer of M2BP (M2BPGi)	473:509	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	12	2	theme	M2BP	1735:1738	arg1	WFA					1701:1703	WFA	1701:1703	WFA of both serum and recombinant M2BP	1701:1738	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	5	3	theme	N-glycan	634:641	arg1	structures					643:652	site-specific N-glycan structures	620:652	site-specific N-glycan structures of serum M2BP	620:666	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	6	4	theme	normal	857:862	arg1	sera					872:875	normal healthy sera	857:875	normal healthy sera (NHS-IP(+))	857:887	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	4	theme	normal	857:862	arg1	NHS-IP					878:883	NHS-IP(+)	878:886	NHS-IP	878:883	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	7	5	theme	NHS-IP	1175:1180	arg1	M2BP					1185:1188	NHS-IP(+) M2BP	1175:1188	NHS-IP(+) M2BP	1175:1188	In NHS-IP(+) M2BP, bi-antennary N-glycan was the main structure, and LacNAc extended to its branches.
34192302	0	6	with	patients	100:107	arg1	fibrosis†					120:128	liver fibrosis†	114:128	liver fibrosis†	114:128	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	2	7	theme	protein	318:324	arg1	levels					295:300	serum levels	289:300	serum levels of Mac2 binding protein (M2BP)	289:331	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	9	8	theme	remarkable	1404:1413	arg1	increase					1415:1422	a remarkable increase	1402:1422	a remarkable increase in branched structures relative to the quantity before enrichment	1402:1488	F4-WFA(+) showed a remarkable increase in branched structures relative to the quantity before enrichment.
34192302	6	9	dep	cirrhosis	1043:1051	arg1	stage					1054:1058	stage 4	1054:1060	stage 4	1054:1060	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	5	10	theme	Glyco-RIDGE	674:684	arg1	method					784:789	Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method	674:789	Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method	674:789	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	5	11	from	IDentification	725:738	arg1	profile					775:781	Elution profile	767:781	Elution profile	767:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	2	12	theme	Mac2	305:308	arg1	M2BP					327:330	M2BP	327:330	M2BP	327:330	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	2	12	theme	Mac2	305:308	arg1	protein					318:324	Mac2 binding protein	305:324	Mac2 binding protein (M2BP)	305:331	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	6	13	dep	stage	1054:1058	arg1	F4-WFA					1063:1068	F4-WFA	1063:1068	F4-WFA	1063:1068	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	8	14	theme	tetra-antennary	1346:1360	arg1	N-glycans					1362:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	13	15	theme	branched	1854:1861	arg1	cluster					1886:1892	dense cluster	1880:1892	dense cluster of LacNAc	1880:1902	On M2BPGi, the highly branched LacNAc, probably dense cluster of LacNAc, would be recognized by WFA.
34192302	13	15	theme	branched	1854:1861	arg1	LacNAc					1863:1868	the highly branched LacNAc	1843:1868	the highly branched LacNAc	1843:1868	On M2BPGi, the highly branched LacNAc, probably dense cluster of LacNAc, would be recognized by WFA.
34192302	0	16	from	protein	76:82	arg1	serum					91:95	the serum	87:95	the serum of patients with liver fibrosis†	87:128	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	6	17	with	patients	1023:1030	arg1	cirrhosis					1043:1051	liver cirrhosis	1037:1051	liver cirrhosis (stage 4; F4-WFA(+))	1037:1072	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	17	with	patients	1023:1030	arg1	M2BP					1091:1094	(4) recombinant M2BP	1075:1094	(4) recombinant M2BP	1075:1094	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	5	18	theme	M2BP	663:666	arg1	structures					643:652	site-specific N-glycan structures	620:652	site-specific N-glycan structures of serum M2BP	620:666	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	2	19	theme	fibrosis	267:274	arg1	progression					276:286	the fibrosis progression	263:286	the fibrosis progression	263:286	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	5	20	theme	signals	756:762	arg1	IDentification					725:738	Glycan heterogeneity-based Relational IDentification	687:738	Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile	687:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	1	21	theme	liver	145:149	arg1	fibrosis					151:158	liver fibrosis	145:158	liver fibrosis	145:158	The extent of liver fibrosis predicts prognosis and is important for determining treatment strategies for chronic hepatitis.
34192302	6	22	theme	liver	945:949	arg1	cirrhosis					951:959	liver cirrhosis	945:959	liver cirrhosis (stage 4; F4-IP(+))	945:979	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	11	23	located	found	1617:1621	arg1	M2BP					1632:1635	serum M2BP	1626:1635	serum M2BP	1626:1635	The LacdiNAc structure was not found in serum M2BP.
34192302	11	23	located	found	1617:1621	arg2	structure					1599:1607	The LacdiNAc structure	1586:1607	The LacdiNAc structure	1586:1607	The LacdiNAc structure was not found in serum M2BP.
34192302	5	24	theme	Elution	767:773	arg1	profile					775:781	Elution profile	767:781	Elution profile	767:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	5	25	from	profile	775:781	arg1	IDentification					725:738	Glycan heterogeneity-based Relational IDentification	687:738	Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile	687:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	12	26	theme	Glycosidase-assisted	1638:1657	arg1	assays					1665:1670	Glycosidase-assisted HISCL assays	1638:1670	Glycosidase-assisted HISCL assays	1638:1670	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	6	27	theme	patients	931:938	arg1	sera					923:926	sera	923:926	sera of patients with liver cirrhosis (stage 4; F4-IP(+))	923:979	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	5	28	theme	Relational	714:723	arg1	IDentification					725:738	Glycan heterogeneity-based Relational IDentification	687:738	Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile	687:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	9	29	from	increase	1415:1422	arg1	structures					1436:1445	branched structures	1427:1445	branched structures relative to the quantity before enrichment	1427:1488	F4-WFA(+) showed a remarkable increase in branched structures relative to the quantity before enrichment.
34192302	2	30	theme	agglutinin	418:427	arg1	lectin					435:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	6	31	theme	WFA-captured	1137:1148	arg1	rM2BP-WFA					1157:1165	rM2BP-WFA(+)	1157:1168	rM2BP-WFA	1157:1165	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	31	theme	WFA-captured	1137:1148	arg1	rM2BP					1150:1154	(5) WFA-captured rM2BP	1133:1154	(5) WFA-captured rM2BP (rM2BP-WFA(+))	1133:1169	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	12	32	with	reactivity	1685:1694	arg1	WFA					1701:1703	WFA	1701:1703	WFA of both serum and recombinant M2BP	1701:1738	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	0	33	theme	N-glycan	0:7	arg1	structures					9:18	N-glycan structures	0:18	N-glycan structures of Wisteria floribunda	0:41	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	3	34	theme	novel	448:452	arg1	marker					465:470	a novel diagnostic marker	446:470	a novel diagnostic marker	446:470	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	3	34	theme	novel	448:452	arg1	isomer					487:492	glycosylation isomer	473:492	glycosylation isomer of M2BP (M2BPGi)	473:509	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	8	35	located	found	1378:1382	arg2	structures					1306:1315	many branched structures	1292:1315	many branched structures	1292:1315	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	8	35	located	found	1378:1382	arg2	N-glycans					1362:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	8	35	located	found	1378:1382	arg1	M2BP					1286:1289	M2BP	1286:1289	M2BP	1286:1289	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	8	35	located	found	1378:1382	arg1	F4-IP					1277:1281	F4-IP	1277:1281	F4-IP	1277:1281	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	12	36	theme	recombinant	1723:1733	arg1	M2BP					1735:1738	recombinant M2BP	1723:1738	recombinant M2BP	1723:1738	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	2	37	theme	floribunda	407:416	arg1	lectin					435:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	0	38	theme	floribunda	32:41	arg1	structures					9:18	N-glycan structures	0:18	N-glycan structures of Wisteria floribunda	0:41	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	8	39	theme	many	1292:1295	arg1	N-glycans					1362:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	8	39	theme	many	1292:1295	arg1	structures					1306:1315	many branched structures	1292:1315	many branched structures	1292:1315	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	6	40	dep	M2BP	986:989	arg1	M2BP					828:831	(1) M2BP	824:831	(1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+))	824:887	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	40	dep	M2BP	986:989	arg1	3					983:983	3	983:983	3	983:983	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	40	dep	M2BP	986:989	arg1	captured					991:998	captured	991:998	captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+))	991:1169	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	40	dep	M2BP	986:989	arg1	M2BP					894:897	(2) M2BP	890:897	(2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+))	890:979	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	7	41	theme	bi-antennary	1191:1202	arg1	structure					1226:1234	the main structure	1217:1234	the main structure	1217:1234	In NHS-IP(+) M2BP, bi-antennary N-glycan was the main structure, and LacNAc extended to its branches.
34192302	7	41	theme	bi-antennary	1191:1202	arg1	N-glycan					1204:1211	bi-antennary N-glycan	1191:1211	bi-antennary N-glycan	1191:1211	In NHS-IP(+) M2BP, bi-antennary N-glycan was the main structure, and LacNAc extended to its branches.
34192302	3	42	theme	glycosylation	473:485	arg1	marker					465:470	a novel diagnostic marker	446:470	a novel diagnostic marker	446:470	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	3	42	theme	glycosylation	473:485	arg1	isomer					487:492	glycosylation isomer	473:492	glycosylation isomer of M2BP (M2BPGi)	473:509	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	0	43	theme	Mac2	63:66	arg1	protein					76:82	Mac2 binding protein	63:82	Mac2 binding protein in the serum of patients with liver fibrosis†	63:128	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	8	44	theme	branched	1297:1304	arg1	N-glycans					1362:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	8	44	theme	branched	1297:1304	arg1	structures					1306:1315	many branched structures	1292:1315	many branched structures	1292:1315	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	12	45	theme	unsialylated	1751:1762	arg1	LacNAc					1777:1782	unsialylated and branched LacNAc	1751:1782	unsialylated and branched LacNAc	1751:1782	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	8	46	theme	tri-antennary	1328:1340	arg1	N-glycans					1362:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	tri-antennary and tetra-antennary N-glycans	1328:1370	In F4-IP(+) M2BP, many branched structures, including tri-antennary and tetra-antennary N-glycans, were found.
34192302	6	47	theme	HEK293	1108:1113	arg1	rM2BP					1122:1126	rM2BP	1122:1126	rM2BP	1122:1126	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	47	theme	HEK293	1108:1113	arg1	cells					1115:1119	HEK293 cells	1108:1119	HEK293 cells (rM2BP)	1108:1127	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	2	48	theme	N-glycan	350:357	arg1	structure					359:367	the N-glycan structure	346:367	the N-glycan structure	346:367	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	12	49	theme	branched	1768:1775	arg1	LacNAc					1777:1782	unsialylated and branched LacNAc	1751:1782	unsialylated and branched LacNAc	1751:1782	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	7	50	theme	main	1221:1224	arg1	structure					1226:1234	the main structure	1217:1234	the main structure	1217:1234	In NHS-IP(+) M2BP, bi-antennary N-glycan was the main structure, and LacNAc extended to its branches.
34192302	7	50	theme	main	1221:1224	arg1	N-glycan					1204:1211	bi-antennary N-glycan	1191:1211	bi-antennary N-glycan	1191:1211	In NHS-IP(+) M2BP, bi-antennary N-glycan was the main structure, and LacNAc extended to its branches.
34192302	4	51	theme	glycan	544:549	arg1	structures					551:560	its glycan structures	540:560	its glycan structures recognized by WFA	540:578	However, its glycan structures recognized by WFA are unclear.
34192302	5	52	theme	site-specific	620:632	arg1	structures					643:652	site-specific N-glycan structures	620:652	site-specific N-glycan structures of serum M2BP	620:666	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	13	53	theme	dense	1880:1884	arg1	cluster					1886:1892	dense cluster	1880:1892	dense cluster of LacNAc	1880:1902	On M2BPGi, the highly branched LacNAc, probably dense cluster of LacNAc, would be recognized by WFA.
34192302	13	53	theme	dense	1880:1884	arg1	LacNAc					1863:1868	the highly branched LacNAc	1843:1868	the highly branched LacNAc	1843:1868	On M2BPGi, the highly branched LacNAc, probably dense cluster of LacNAc, would be recognized by WFA.
34192302	6	54	dep	M2BP	1091:1094	arg1	4					1076:1076	4	1076:1076	4	1076:1076	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	55	theme	recombinant	1079:1089	arg1	cirrhosis					1043:1051	liver cirrhosis	1037:1051	liver cirrhosis (stage 4; F4-WFA(+))	1037:1072	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	55	theme	recombinant	1079:1089	arg1	M2BP					1091:1094	(4) recombinant M2BP	1075:1094	(4) recombinant M2BP	1075:1094	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	2	56	theme	serum	289:293	arg1	levels					295:300	serum levels	289:300	serum levels of Mac2 binding protein (M2BP)	289:331	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	6	57	theme	healthy	864:870	arg1	sera					872:875	normal healthy sera	857:875	normal healthy sera (NHS-IP(+))	857:887	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	57	theme	healthy	864:870	arg1	NHS-IP					878:883	NHS-IP(+)	878:886	NHS-IP	878:883	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	58	theme	liver	1037:1041	arg1	cirrhosis					1043:1051	liver cirrhosis	1037:1051	liver cirrhosis (stage 4; F4-WFA(+))	1037:1072	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	58	theme	liver	1037:1041	arg1	M2BP					1091:1094	(4) recombinant M2BP	1075:1094	(4) recombinant M2BP	1075:1094	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	59	theme	patients	1023:1030	arg1	serum					1014:1018	serum	1014:1018	serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+))	1014:1169	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	10	60	dep	structures	1561:1570	arg1	both					1512:1515	both	1512:1515	both	1512:1515	In recombinant M2BP, both no sialylated-LacdiNAc and -branched LacNAc structures were emerged.
34192302	10	60	dep	structures	1561:1570	arg1	-branched					1544:1552	-branched	1544:1552	-branched	1544:1552	In recombinant M2BP, both no sialylated-LacdiNAc and -branched LacNAc structures were emerged.
34192302	2	61	theme	binding	310:316	arg1	M2BP					327:330	M2BP	327:330	M2BP	327:330	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	2	61	theme	binding	310:316	arg1	protein					318:324	Mac2 binding protein	305:324	Mac2 binding protein (M2BP)	305:331	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	12	62	theme	serum	1713:1717	arg1	WFA					1701:1703	WFA	1701:1703	WFA of both serum and recombinant M2BP	1701:1738	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	10	63	dep	both	1512:1515	arg1	sialylated-LacdiNAc					1520:1538	no sialylated-LacdiNAc	1517:1538	no sialylated-LacdiNAc	1517:1538	In recombinant M2BP, both no sialylated-LacdiNAc and -branched LacNAc structures were emerged.
34192302	1	64	theme	treatment	212:220	arg1	strategies					222:231	treatment strategies	212:231	treatment strategies for chronic hepatitis	212:253	The extent of liver fibrosis predicts prognosis and is important for determining treatment strategies for chronic hepatitis.
34192302	7	65	from	structure	1226:1234	arg1	M2BP					1185:1188	NHS-IP(+) M2BP	1175:1188	NHS-IP(+) M2BP	1175:1188	In NHS-IP(+) M2BP, bi-antennary N-glycan was the main structure, and LacNAc extended to its branches.
34192302	9	66	theme	branched	1427:1434	arg1	structures					1436:1445	branched structures	1427:1445	branched structures relative to the quantity before enrichment	1427:1488	F4-WFA(+) showed a remarkable increase in branched structures relative to the quantity before enrichment.
34192302	5	67	theme	heterogeneity-based	694:712	arg1	IDentification					725:738	Glycan heterogeneity-based Relational IDentification	687:738	Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile	687:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	9	68	theme	relative	1447:1454	arg1	structures					1436:1445	branched structures	1427:1445	branched structures relative to the quantity before enrichment	1427:1488	F4-WFA(+) showed a remarkable increase in branched structures relative to the quantity before enrichment.
34192302	6	69	dep	M2BP	894:897	arg1	2					891:891	2	891:891	2	891:891	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	12	70	theme	recombinant	1799:1809	arg1	part					1791:1794	part	1791:1794	part of recombinant	1791:1809	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	5	71	theme	serum	657:661	arg1	M2BP					663:666	serum M2BP	657:666	serum M2BP	657:666	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	10	72	theme	recombinant	1494:1504	arg1	M2BP					1506:1509	recombinant M2BP	1494:1509	recombinant M2BP	1494:1509	In recombinant M2BP, both no sialylated-LacdiNAc and -branched LacNAc structures were emerged.
34192302	5	73	theme	Glycopeptide	743:754	arg1	signals					756:762	Glycopeptide signals	743:762	Glycopeptide signals on Elution profile	743:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	5	74	from	signals	756:762	arg1	profile					775:781	Elution profile	767:781	Elution profile	767:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	10	75	theme	LacNAc	1554:1559	arg1	structures					1561:1570	both no sialylated-LacdiNAc and -branched LacNAc structures	1512:1570	both no sialylated-LacdiNAc and -branched LacNAc structures	1512:1570	In recombinant M2BP, both no sialylated-LacdiNAc and -branched LacNAc structures were emerged.
34192302	6	76	with	patients	931:938	arg1	cirrhosis					951:959	liver cirrhosis	945:959	liver cirrhosis (stage 4; F4-IP(+))	945:979	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	12	77	theme	HISCL	1659:1663	arg1	assays					1665:1670	Glycosidase-assisted HISCL assays	1638:1670	Glycosidase-assisted HISCL assays	1638:1670	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	1	78	theme	fibrosis	151:158	arg1	extent					135:140	The extent	131:140	The extent of liver fibrosis	131:158	The extent of liver fibrosis predicts prognosis and is important for determining treatment strategies for chronic hepatitis.
34192302	1	78	theme	fibrosis	151:158	arg1	important					186:194	important	186:194	important	186:194	The extent of liver fibrosis predicts prognosis and is important for determining treatment strategies for chronic hepatitis.
34192302	5	79	dep	Glyco-RIDGE	674:684	arg1	IDentification					725:738	Glycan heterogeneity-based Relational IDentification	687:738	Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile	687:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	0	80	theme	patients	100:107	arg1	serum					91:95	the serum	87:95	the serum of patients with liver fibrosis†	87:128	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	6	81	dep	cirrhosis	951:959	arg1	stage					962:966	stage 4	962:968	stage 4	962:968	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	0	82	theme	liver	114:118	arg1	fibrosis†					120:128	liver fibrosis†	114:128	liver fibrosis†	114:128	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	6	83	dep	stage	962:966	arg1	F4-IP					971:975	F4-IP	971:975	F4-IP	971:975	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	13	84	theme	LacNAc	1897:1902	arg1	cluster					1886:1892	dense cluster	1880:1892	dense cluster of LacNAc	1880:1902	On M2BPGi, the highly branched LacNAc, probably dense cluster of LacNAc, would be recognized by WFA.
34192302	13	84	theme	LacNAc	1897:1902	arg1	LacNAc					1863:1868	the highly branched LacNAc	1843:1868	the highly branched LacNAc	1843:1868	On M2BPGi, the highly branched LacNAc, probably dense cluster of LacNAc, would be recognized by WFA.
34192302	9	85	dep	F4-WFA	1385:1390	arg1	+					1392:1392	+	1392:1392	+	1392:1392	F4-WFA(+) showed a remarkable increase in branched structures relative to the quantity before enrichment.
34192302	11	86	theme	serum	1626:1630	arg1	M2BP					1632:1635	serum M2BP	1626:1635	serum M2BP	1626:1635	The LacdiNAc structure was not found in serum M2BP.
34192302	2	87	theme	WFA	430:432	arg1	lectin					435:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	3	88	theme	diagnostic	454:463	arg1	marker					465:470	a novel diagnostic marker	446:470	a novel diagnostic marker	446:470	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	3	88	theme	diagnostic	454:463	arg1	isomer					487:492	glycosylation isomer	473:492	glycosylation isomer of M2BP (M2BPGi)	473:509	As a novel diagnostic marker, glycosylation isomer of M2BP (M2BPGi) has been developed.
34192302	6	89	dep	M2BP	828:831	arg1	types					817:821	five sample types	805:821	five sample types	805:821	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	6	89	dep	M2BP	828:831	arg1	1					825:825	1	825:825	1	825:825	We evaluated five sample types: (1) M2BP immunoprecipitated from normal healthy sera (NHS-IP(+)), (2) M2BP immunoprecipitated from sera of patients with liver cirrhosis (stage 4; F4-IP(+)), (3) M2BP captured with WFA from serum of patients with liver cirrhosis (stage 4; F4-WFA(+)), (4) recombinant M2BP produced by HEK293 cells (rM2BP) and (5) WFA-captured rM2BP (rM2BP-WFA(+)).
34192302	12	90	gly	unsialylated	1751:1762	arg1	LacNAc					1777:1782	unsialylated and branched LacNAc	1751:1782	unsialylated and branched LacNAc	1751:1782	Glycosidase-assisted HISCL assays suggest that reactivity with WFA of both serum and recombinant M2BP depends on unsialylated and branched LacNAc and in part of recombinant depends on LacdiNAc.
34192302	2	91	theme	Wisteria	398:405	arg1	lectin					435:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	Wisteria floribunda agglutinin (WFA) lectin	398:440	During the fibrosis progression, serum levels of Mac2 binding protein (M2BP) increase and the N-glycan structure changes to enable binding to Wisteria floribunda agglutinin (WFA) lectin.
34192302	0	92	theme	binding	68:74	arg1	protein					76:82	Mac2 binding protein	63:82	Mac2 binding protein in the serum of patients with liver fibrosis†	63:128	N-glycan structures of Wisteria floribunda agglutinin-positive Mac2 binding protein in the serum of patients with liver fibrosis†.
34192302	5	93	theme	Glycan	687:692	arg1	IDentification					725:738	Glycan heterogeneity-based Relational IDentification	687:738	Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile	687:781	In this study, we analyzed site-specific N-glycan structures of serum M2BP using Glyco-RIDGE (Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile) method.
34192302	11	94	theme	LacdiNAc	1590:1597	arg1	structure					1599:1607	The LacdiNAc structure	1586:1607	The LacdiNAc structure	1586:1607	The LacdiNAc structure was not found in serum M2BP.
34192302	1	95	theme	chronic	237:243	arg1	hepatitis					245:253	chronic hepatitis	237:253	chronic hepatitis	237:253	The extent of liver fibrosis predicts prognosis and is important for determining treatment strategies for chronic hepatitis.
31880395	2	0	dep	enolate	300:306	arg1	results					308:314	results	308:314	results in the stereospecific construction of β-linked C-glycosides	308:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	2	1	link	β-linked	354:361	arg1	C-glycosides					363:374	β-linked C-glycosides	354:374	β-linked C-glycosides	354:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	0	2	theme	Versatile	0:8	arg1	Glycosyl					10:17	Versatile Glycosyl	0:17	Versatile Glycosyl	0:17	Versatile Glycosyl Sulfonates in β-Selective C-Glycosylation.
31880395	2	3	theme	C-glycosides	363:374	arg1	construction					338:349	the stereospecific construction	319:349	the stereospecific construction of β-linked C-glycosides	319:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	1	4	from	mimetics	158:165	arg1	products					125:132	many bioactive natural products	102:132	many bioactive natural products	102:132	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	1	5	theme	common	86:91	arg1	motif					93:97	a common motif	84:97	a common motif in many bioactive natural products	84:132	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	1	5	theme	common	86:91	arg1	C-Glycosides					62:73	C-Glycosides	62:73	C-Glycosides	62:73	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	4	6	theme	C-glycoside	514:524	arg1	analogues					526:534	C-glycoside analogues	514:534	C-glycoside analogues	514:534	The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
31880395	4	6	theme	C-glycoside	514:524	arg1	mimetics					583:590	C-disaccharide mimetics	568:590	C-disaccharide mimetics	568:590	The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
31880395	2	7	theme	stereospecific	323:336	arg1	construction					338:349	the stereospecific construction	319:349	the stereospecific construction of β-linked C-glycosides	319:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	3	8	theme	acceptors	412:420	arg1	disaccharides					444:456	disaccharides	444:456	disaccharides	444:456	This reaction tolerates a range of acceptors and donors, including disaccharides.
31880395	3	8	theme	acceptors	412:420	arg1	range					403:407	a range	401:407	a range	401:407	This reaction tolerates a range of acceptors and donors, including disaccharides.
31880395	1	9	theme	many	102:105	arg1	products					125:132	many bioactive natural products	102:132	many bioactive natural products	102:132	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	1	10	theme	bioactive	107:115	arg1	products					125:132	many bioactive natural products	102:132	many bioactive natural products	102:132	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	0	11	theme	β-Selective	33:43	arg1	C-Glycosylation					45:59	β-Selective C-Glycosylation	33:59	β-Selective C-Glycosylation	33:59	Versatile Glycosyl Sulfonates in β-Selective C-Glycosylation.
31880395	4	12	theme	C-disaccharide	568:581	arg1	mimetics					583:590	C-disaccharide mimetics	568:590	C-disaccharide mimetics	568:590	The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
31880395	1	13	theme	natural	117:123	arg1	products					125:132	many bioactive natural products	102:132	many bioactive natural products	102:132	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	3	14	theme	donors	426:431	arg1	disaccharides					444:456	disaccharides	444:456	disaccharides	444:456	This reaction tolerates a range of acceptors and donors, including disaccharides.
31880395	3	14	theme	donors	426:431	arg1	range					403:407	a range	401:407	a range	401:407	This reaction tolerates a range of acceptors and donors, including disaccharides.
31880395	2	15	theme	sulfonyl	219:226	arg1	chloride					228:235	a sulfonyl chloride	217:235	a sulfonyl chloride	217:235	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	2	16	theme	β-linked	354:361	arg1	C-glycosides					363:374	β-linked C-glycosides	354:374	β-linked C-glycosides	354:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	2	17	theme	glycosyl	273:280	arg1	sulfonate					282:290	the resultant glycosyl sulfonate	259:290	the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides	259:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	4	18	theme	resulting	463:471	arg1	products					473:480	The resulting products	459:480	The resulting products	459:480	The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
31880395	2	19	theme	resultant	263:271	arg1	sulfonate					282:290	the resultant glycosyl sulfonate	259:290	the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides	259:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	1	20	theme	important	138:146	arg1	mimetics					158:165	important glycoside mimetics	138:165	important glycoside mimetics	138:165	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	1	21	from	motif	93:97	arg1	products					125:132	many bioactive natural products	102:132	many bioactive natural products	102:132	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	2	22	with	sulfonate	282:290	arg1	enolate					300:306	an enolate	297:306	an enolate results in the stereospecific construction of β-linked C-glycosides	297:374	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
31880395	1	23	theme	glycoside	148:156	arg1	mimetics					158:165	important glycoside mimetics	138:165	important glycoside mimetics	138:165	C-Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics.
31880395	4	24	theme	β-glycoconjugates	539:555	arg1	analogues					526:534	C-glycoside analogues	514:534	C-glycoside analogues	514:534	The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
31880395	4	24	theme	β-glycoconjugates	539:555	arg1	mimetics					583:590	C-disaccharide mimetics	568:590	C-disaccharide mimetics	568:590	The resulting products can be readily derivatized into C-glycoside analogues of β-glycoconjugates, including C-disaccharide mimetics.
31880395	2	25	with	hemiacetal	201:210	arg1	chloride					228:235	a sulfonyl chloride	217:235	a sulfonyl chloride	217:235	We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β-linked C-glycosides.
33300777	4	0	theme	identical	883:891	arg1	sequence					901:908	an identical peptide sequence	880:908	an identical peptide sequence	880:908	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	6	1	theme	disialylated	1137:1148	arg1	target					1251:1256	the target	1247:1256	the target	1247:1256	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	1	theme	disialylated	1137:1148	arg1	A2G2S2					1159:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	1	theme	disialylated	1137:1148	arg1	proof					1080:1084	proof	1080:1084	proof of the principle	1080:1101	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	8	2	theme	selected	1684:1691	arg1	aptamers					1693:1700	the selected aptamers	1680:1700	the selected aptamers	1680:1700	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	3	3	with	aptamers	531:538	arg1	structure					579:587	a complex structure	569:587	a complex structure	569:587	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	2	4	theme	glycans	302:308	arg1	homology					266:273	the structural homology	251:273	the structural homology	251:273	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	2	4	theme	glycans	302:308	arg1	immunogenicity					284:297	weak immunogenicity	279:297	weak immunogenicity of glycans	279:308	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	4	5	theme	nonglycosylated	850:864	arg1	analogue					866:873	a nonglycosylated analogue	848:873	a nonglycosylated analogue with an identical peptide sequence	848:908	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	4	6	theme	peptide-imprinted	656:672	arg1	platform					719:726	a versatile platform	707:726	a versatile platform	707:726	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	4	6	theme	peptide-imprinted	656:672	arg1	MNPs					698:701	MNPs	698:701	MNPs	698:701	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	4	6	theme	peptide-imprinted	656:672	arg1	nanoparticles					683:695	peptide-imprinted magnetic nanoparticles	656:695	peptide-imprinted magnetic nanoparticles (MNPs)	656:702	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	3	7	theme	specific	547:554	arg1	glycans					556:562	specific glycans	547:562	specific glycans	547:562	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	6	8	theme	digalactosylated	1120:1135	arg1	target					1251:1256	the target	1247:1256	the target	1247:1256	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	8	theme	digalactosylated	1120:1135	arg1	A2G2S2					1159:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	8	theme	digalactosylated	1120:1135	arg1	proof					1080:1084	proof	1080:1084	proof of the principle	1080:1101	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	9	9	theme	tedious	1728:1734	arg1	process					1755:1761	a tedious glycan preparation process	1726:1761	a tedious glycan preparation process	1726:1761	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	1	10	theme	binders	198:204	arg1	development					167:177	the development	163:177	the development of glycan-specific binders	163:204	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	1	10	theme	binders	198:204	arg1	important					231:239	important	231:239	important	231:239	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	9	11	theme	preparation	1743:1753	arg1	process					1755:1761	a tedious glycan preparation process	1726:1761	a tedious glycan preparation process	1726:1761	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	5	12	theme	negative	975:982	arg1	steps					994:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps were carried out to guide the directed evolution of glycan-binding aptamers.
33300777	3	13	theme	complex	571:577	arg1	structure					579:587	a complex structure	569:587	a complex structure	569:587	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	4	14	gly	nonglycosylated	850:864	arg1	analogue					866:873	a nonglycosylated analogue	848:873	a nonglycosylated analogue with an identical peptide sequence	848:908	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	4	15	theme	versatile	709:717	arg1	platform					719:726	a versatile platform	707:726	a versatile platform	707:726	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	4	15	theme	versatile	709:717	arg1	nanoparticles					683:695	peptide-imprinted magnetic nanoparticles	656:695	peptide-imprinted magnetic nanoparticles (MNPs)	656:702	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	1	16	theme	valuable	123:130	arg1	biomarkers					132:141	valuable biomarkers	123:141	valuable biomarkers for disease states	123:160	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	1	16	theme	valuable	123:130	arg1	structures					108:117	Abnormal glycan structures	92:117	Abnormal glycan structures	92:117	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	4	17	theme	negative	930:937	arg1	selection					939:947	negative selection	930:947	negative selection	930:947	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	2	18	theme	weak	279:282	arg1	immunogenicity					284:297	weak immunogenicity	279:297	weak immunogenicity of glycans	279:308	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	5	19	theme	selection	984:992	arg1	steps					994:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps were carried out to guide the directed evolution of glycan-binding aptamers.
33300777	5	20	theme	positive	962:969	arg1	steps					994:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps were carried out to guide the directed evolution of glycan-binding aptamers.
33300777	9	21	theme	intrinsic	1799:1807	arg1	conformation					1818:1829	the intrinsic flexible conformation	1795:1829	the intrinsic flexible conformation of natural glycans	1795:1848	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	8	22	theme	fluorescent	1506:1516	arg1	aptamers					1480:1487	carboxyfluorescein (FAM)-labeled aptamers	1447:1487	carboxyfluorescein (FAM)-labeled aptamers	1447:1487	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	8	22	theme	fluorescent	1506:1516	arg1	reagents					1526:1533	fluorescent imaging reagents	1506:1533	fluorescent imaging reagents	1506:1533	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	2	23	theme	structural	255:264	arg1	homology					266:273	the structural homology	251:273	the structural homology	251:273	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	2	24	from	hurdles	321:327	arg1	evolution					336:344	the evolution	332:344	the evolution of antibodies	332:358	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	9	25	theme	conformation	1818:1829	arg1	favorable					1775:1783	favorable	1775:1783	favorable	1775:1783	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	4	26	gly	glycoprotein	779:790	arg1	glycoprotein					779:790	a native glycoprotein	770:790	a native glycoprotein	770:790	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	9	27	theme	natural	1834:1840	arg1	glycans					1842:1848	natural glycans	1834:1848	natural glycans	1834:1848	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	4	28	gly	glycopeptide	731:742	arg2	glycopeptide					731:742	a glycopeptide	729:742	a glycopeptide tryptically digested from a native glycoprotein	729:790	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	2	29	theme	aptamers	465:472	arg1	selection					440:448	the selection	436:448	the selection of anti-glycan aptamers	436:472	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	8	30	theme	cancerous	1570:1578	arg1	cells					1586:1590	cancerous liver cells	1570:1590	cancerous liver cells	1570:1590	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	2	31	theme	complex	392:398	arg1	glycans					400:406	complex glycans	392:406	complex glycans	392:406	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	0	32	theme	Efficient	0:8	arg1	Screening					10:18	Efficient Screening	0:18	Efficient Screening of Glycan-Specific Aptamers	0:46	Efficient Screening of Glycan-Specific Aptamers Using a Glycosylated Peptide as a Scaffold.
33300777	1	33	theme	Abnormal	92:99	arg1	biomarkers					132:141	valuable biomarkers	123:141	valuable biomarkers for disease states	123:160	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	1	33	theme	Abnormal	92:99	arg1	structures					108:117	Abnormal glycan structures	92:117	Abnormal glycan structures	92:117	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	6	34	theme	principle	1093:1101	arg1	A2G2S2					1159:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	34	theme	principle	1093:1101	arg1	proof					1080:1084	proof	1080:1084	proof of the principle	1080:1101	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	8	35	theme	cells	1586:1590	arg1	differentiation					1551:1565	successful differentiation	1540:1565	successful differentiation of cancerous liver cells over normal liver cells	1540:1614	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	7	36	theme	satisfied	1327:1335	arg1	aptamers					1349:1356	two satisfied anti-A2G2S2 aptamers	1323:1356	two satisfied anti-A2G2S2 aptamers	1323:1356	With the glycoprotein transferrin as a source of target glycan, two satisfied anti-A2G2S2 aptamers were selected within seven rounds.
33300777	8	37	theme	normal	1597:1602	arg1	cells					1610:1614	normal liver cells	1597:1614	normal liver cells	1597:1614	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	10	38	theme	challenging	1929:1939	arg1	applications					1941:1952	challenging applications	1929:1952	challenging applications such as cancer targeting	1929:1977	Therefore, it holds great promise for developing glycan-specific aptamers for challenging applications such as cancer targeting.
33300777	10	38	theme	challenging	1929:1939	arg1	targeting					1969:1977	cancer targeting	1962:1977	cancer targeting	1962:1977	Therefore, it holds great promise for developing glycan-specific aptamers for challenging applications such as cancer targeting.
33300777	8	39	theme	cancerous	1424:1432	arg1	cells					1440:1444	cancerous liver cells	1424:1444	cancerous liver cells	1424:1444	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	0	40	theme	Aptamers	39:46	arg1	Screening					10:18	Efficient Screening	0:18	Efficient Screening of Glycan-Specific Aptamers	0:46	Efficient Screening of Glycan-Specific Aptamers Using a Glycosylated Peptide as a Scaffold.
33300777	5	41	theme	glycan-binding	1052:1065	arg1	aptamers					1067:1074	glycan-binding aptamers	1052:1074	glycan-binding aptamers	1052:1074	Alternating positive and negative selection steps were carried out to guide the directed evolution of glycan-binding aptamers.
33300777	3	42	theme	new	496:498	arg1	approach					500:507	a new approach	494:507	a new approach to efficiently screen aptamers toward specific glycans with a complex structure	494:587	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	7	43	theme	target	1308:1313	arg1	glycan					1315:1320	target glycan	1308:1320	target glycan	1308:1320	With the glycoprotein transferrin as a source of target glycan, two satisfied anti-A2G2S2 aptamers were selected within seven rounds.
33300777	10	44	theme	cancer	1962:1967	arg1	targeting					1969:1977	cancer targeting	1962:1977	cancer targeting	1962:1977	Therefore, it holds great promise for developing glycan-specific aptamers for challenging applications such as cancer targeting.
33300777	8	45	theme	aptamers	1693:1700	arg1	feasibility					1665:1675	the application feasibility	1649:1675	the application feasibility of the selected aptamers	1649:1700	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	6	46	theme	N-glycan	1150:1157	arg1	target					1251:1256	the target	1247:1256	the target	1247:1256	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	46	theme	N-glycan	1150:1157	arg1	A2G2S2					1159:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	46	theme	N-glycan	1150:1157	arg1	proof					1080:1084	proof	1080:1084	proof of the principle	1080:1101	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	7	47	theme	glycoprotein	1268:1279	arg1	transferrin					1281:1291	the glycoprotein transferrin	1264:1291	the glycoprotein transferrin as a source of target glycan	1264:1320	With the glycoprotein transferrin as a source of target glycan, two satisfied anti-A2G2S2 aptamers were selected within seven rounds.
33300777	4	48	theme	peptide	893:899	arg1	sequence					901:908	an identical peptide sequence	880:908	an identical peptide sequence	880:908	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	1	49	theme	glycan-specific	182:196	arg1	binders					198:204	glycan-specific binders	182:204	glycan-specific binders	182:204	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	9	50	theme	glycan	1736:1741	arg1	process					1755:1761	a tedious glycan preparation process	1726:1761	a tedious glycan preparation process	1726:1761	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	4	51	theme	magnetic	674:681	arg1	platform					719:726	a versatile platform	707:726	a versatile platform	707:726	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	4	51	theme	magnetic	674:681	arg1	MNPs					698:701	MNPs	698:701	MNPs	698:701	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	4	51	theme	magnetic	674:681	arg1	nanoparticles					683:695	peptide-imprinted magnetic nanoparticles	656:695	peptide-imprinted magnetic nanoparticles (MNPs)	656:702	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	8	52	theme	-labeled	1471:1478	arg1	aptamers					1480:1487	carboxyfluorescein (FAM)-labeled aptamers	1447:1487	carboxyfluorescein (FAM)-labeled aptamers	1447:1487	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	8	52	theme	-labeled	1471:1478	arg1	reagents					1526:1533	fluorescent imaging reagents	1506:1533	fluorescent imaging reagents	1506:1533	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	3	53	gly	glycosylated	598:609	arg1	peptide					611:617	a glycosylated peptide	596:617	a glycosylated peptide	596:617	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	3	53	gly	glycosylated	598:609	arg1	scaffold					624:631	a scaffold	622:631	a scaffold	622:631	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	3	54	theme	glycosylated	598:609	arg1	peptide					611:617	a glycosylated peptide	596:617	a glycosylated peptide	596:617	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	3	54	theme	glycosylated	598:609	arg1	scaffold					624:631	a scaffold	622:631	a scaffold	622:631	Herein, we present a new approach to efficiently screen aptamers toward specific glycans with a complex structure, using a glycosylated peptide as a scaffold.
33300777	10	55	theme	glycan-specific	1900:1914	arg1	aptamers					1916:1923	glycan-specific aptamers	1900:1923	glycan-specific aptamers for challenging applications such as cancer targeting	1900:1977	Therefore, it holds great promise for developing glycan-specific aptamers for challenging applications such as cancer targeting.
33300777	5	56	theme	Alternating	950:960	arg1	steps					994:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps	950:998	Alternating positive and negative selection steps were carried out to guide the directed evolution of glycan-binding aptamers.
33300777	8	57	theme	imaging	1518:1524	arg1	aptamers					1480:1487	carboxyfluorescein (FAM)-labeled aptamers	1447:1487	carboxyfluorescein (FAM)-labeled aptamers	1447:1487	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	8	57	theme	imaging	1518:1524	arg1	reagents					1526:1533	fluorescent imaging reagents	1506:1533	fluorescent imaging reagents	1506:1533	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	1	58	theme	disease	147:153	arg1	states					155:160	disease states	147:160	disease states	147:160	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	9	59	theme	flexible	1809:1816	arg1	conformation					1818:1829	the intrinsic flexible conformation	1795:1829	the intrinsic flexible conformation of natural glycans	1795:1848	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	4	60	with	analogue	866:873	arg1	sequence					901:908	an identical peptide sequence	880:908	an identical peptide sequence	880:908	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	8	61	theme	successful	1540:1549	arg1	differentiation					1551:1565	successful differentiation	1540:1565	successful differentiation of cancerous liver cells over normal liver cells	1540:1614	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	2	62	theme	major	315:319	arg1	hurdles					321:327	major hurdles	315:327	major hurdles in the evolution of antibodies	315:358	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	9	63	theme	glycans	1842:1848	arg1	conformation					1818:1829	the intrinsic flexible conformation	1795:1829	the intrinsic flexible conformation of natural glycans	1795:1848	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	6	64	gly	disialylated	1137:1148	arg1	target					1251:1256	the target	1247:1256	the target	1247:1256	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	64	gly	disialylated	1137:1148	arg1	A2G2S2					1159:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	64	gly	disialylated	1137:1148	arg1	proof					1080:1084	proof	1080:1084	proof of the principle	1080:1101	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	9	65	dep	favorable	1775:1783	arg1	expose					1785:1790	expose	1785:1790	expose	1785:1790	This approach obviated a tedious glycan preparation process and allowed favorable expose of the intrinsic flexible conformation of natural glycans.
33300777	6	66	theme	biantennary	1108:1118	arg1	target					1251:1256	the target	1247:1256	the target	1247:1256	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	66	theme	biantennary	1108:1118	arg1	A2G2S2					1159:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	the biantennary digalactosylated disialylated N-glycan A2G2S2	1104:1164	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	6	66	theme	biantennary	1108:1118	arg1	proof					1080:1084	proof	1080:1084	proof of the principle	1080:1101	As proof of the principle, the biantennary digalactosylated disialylated N-glycan A2G2S2, against which there have been no antibodies and lectins so far, was employed as the target.
33300777	8	67	theme	liver	1580:1584	arg1	cells					1586:1590	cancerous liver cells	1570:1590	cancerous liver cells	1570:1590	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	4	68	theme	native	772:777	arg1	glycoprotein					779:790	a native glycoprotein	770:790	a native glycoprotein	770:790	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	2	69	theme	glycans	400:406	arg1	availability					376:387	the poor availability	367:387	the poor availability of complex glycans	367:406	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	7	70	theme	anti-A2G2S2	1337:1347	arg1	aptamers					1349:1356	two satisfied anti-A2G2S2 aptamers	1323:1356	two satisfied anti-A2G2S2 aptamers	1323:1356	With the glycoprotein transferrin as a source of target glycan, two satisfied anti-A2G2S2 aptamers were selected within seven rounds.
33300777	2	71	theme	anti-glycan	453:463	arg1	aptamers					465:472	anti-glycan aptamers	453:472	anti-glycan aptamers	453:472	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	0	72	theme	Glycan-Specific	23:37	arg1	Aptamers					39:46	Glycan-Specific Aptamers	23:46	Glycan-Specific Aptamers	23:46	Efficient Screening of Glycan-Specific Aptamers Using a Glycosylated Peptide as a Scaffold.
33300777	1	73	theme	glycan	101:106	arg1	biomarkers					132:141	valuable biomarkers	123:141	valuable biomarkers for disease states	123:160	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	1	73	theme	glycan	101:106	arg1	structures					108:117	Abnormal glycan structures	92:117	Abnormal glycan structures	92:117	Abnormal glycan structures are valuable biomarkers for disease states; the development of glycan-specific binders is thereby significantly important.
33300777	10	74	theme	great	1871:1875	arg1	promise					1877:1883	great promise	1871:1883	great promise for developing glycan-specific aptamers for challenging applications such as cancer targeting	1871:1977	Therefore, it holds great promise for developing glycan-specific aptamers for challenging applications such as cancer targeting.
33300777	8	75	theme	liver	1604:1608	arg1	cells					1610:1614	normal liver cells	1597:1614	normal liver cells	1597:1614	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	7	76	gly	glycoprotein	1268:1279	arg1	glycoprotein					1268:1279	the glycoprotein transferrin	1264:1291	the glycoprotein transferrin as a source of target glycan	1264:1320	With the glycoprotein transferrin as a source of target glycan, two satisfied anti-A2G2S2 aptamers were selected within seven rounds.
33300777	7	77	theme	glycan	1315:1320	arg1	source					1298:1303	a source	1296:1303	a source of target glycan	1296:1320	With the glycoprotein transferrin as a source of target glycan, two satisfied anti-A2G2S2 aptamers were selected within seven rounds.
33300777	4	78	theme	positive	822:829	arg1	selection					831:839	positive selection	822:839	positive selection	822:839	In this method, using peptide-imprinted magnetic nanoparticles (MNPs) as a versatile platform, a glycopeptide tryptically digested from a native glycoprotein was selectively entrapped for positive selection, while a nonglycosylated analogue with an identical peptide sequence was synthesized for negative selection.
33300777	0	79	theme	Glycosylated	56:67	arg1	Peptide					69:75	a Glycosylated Peptide	54:75	a Glycosylated Peptide	54:75	Efficient Screening of Glycan-Specific Aptamers Using a Glycosylated Peptide as a Scaffold.
33300777	0	79	theme	Glycosylated	56:67	arg1	Scaffold					82:89	a Scaffold	80:89	a Scaffold	80:89	Efficient Screening of Glycan-Specific Aptamers Using a Glycosylated Peptide as a Scaffold.
33300777	5	80	theme	aptamers	1067:1074	arg1	evolution					1039:1047	the directed evolution	1026:1047	the directed evolution of glycan-binding aptamers	1026:1074	Alternating positive and negative selection steps were carried out to guide the directed evolution of glycan-binding aptamers.
33300777	8	81	theme	liver	1434:1438	arg1	cells					1440:1444	cancerous liver cells	1424:1444	cancerous liver cells	1424:1444	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	2	82	theme	antibodies	349:358	arg1	evolution					336:344	the evolution	332:344	the evolution of antibodies	332:358	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
33300777	5	83	theme	directed	1030:1037	arg1	evolution					1039:1047	the directed evolution	1026:1047	the directed evolution of glycan-binding aptamers	1026:1074	Alternating positive and negative selection steps were carried out to guide the directed evolution of glycan-binding aptamers.
33300777	8	84	theme	application	1653:1663	arg1	feasibility					1665:1675	the application feasibility	1649:1675	the application feasibility of the selected aptamers	1649:1700	Since A2G2S2 is upregulated in cancerous liver cells, carboxyfluorescein (FAM)-labeled aptamers were prepared as fluorescent imaging reagents, and successful differentiation of cancerous liver cells over normal liver cells was achieved, which demonstrated the application feasibility of the selected aptamers.
33300777	2	85	theme	poor	371:374	arg1	availability					376:387	the poor availability	367:387	the poor availability of complex glycans	367:406	However, the structural homology and weak immunogenicity of glycans pose major hurdles in the evolution of antibodies, while the poor availability of complex glycans also has extremely hindered the selection of anti-glycan aptamers.
34888356	6	0	theme	donors	1054:1059	arg1	sera					1035:1038	the sera	1031:1038	the sera of 47 healthy donors and 47 BD patients	1031:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	10	1	contain	containing	2110:2119	arg2	epitopes					2133:2140	sialic acid epitopes	2121:2140	sialic acid epitopes	2121:2140	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	10	1	contain	containing	2110:2119	arg1	structures					2099:2108	isomeric structures	2090:2108	isomeric structures containing sialic acid epitopes	2090:2140	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	8	2	theme	high	1719:1722	arg1	sensitivity					1724:1734	high sensitivity	1719:1734	high sensitivity	1719:1734	Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers.
34888356	6	3	theme	BD	1206:1207	arg1	glycans					1216:1222	BD target glycans	1206:1222	BD target glycans	1206:1222	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	6	4	theme	MALDI-TOF	1164:1172	arg1	spectrometry					1150:1161	flight mass spectrometry	1138:1161	flight mass spectrometry (MALDI-TOF MS)	1138:1176	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	6	4	theme	MALDI-TOF	1164:1172	arg1	MS					1174:1175	MALDI-TOF MS	1164:1175	MALDI-TOF MS	1164:1175	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	7	5	with	isomers	1492:1498	arg1	epitopes					1517:1524	sialic acid epitopes	1505:1524	sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2	1505:1637	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	6	theme	monitoring	1430:1439	arg1	-MS.					1446:1449	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	11	7	theme	other	2288:2292	arg1	diseases					2301:2308	other immune diseases	2288:2308	other immune diseases	2288:2308	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	10	8	attach	present	1994:2000	arg2	we					1991:1992	we	1991:1992	we	1991:1992	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	10	8	attach	present	1994:2000	arg1	study					1984:1988	this study	1979:1988	this study	1979:1988	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	1	9	theme	immune	157:162	arg1	disease					164:170	an immune disease	154:170	an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death	154:293	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34888356	1	9	theme	immune	157:162	arg1	disease					138:144	Behcet's disease	129:144	Behcet's disease (BD)	129:149	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34888356	6	10	theme	flight	1138:1143	arg1	spectrometry					1150:1161	flight mass spectrometry	1138:1161	flight mass spectrometry (MALDI-TOF MS)	1138:1176	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	6	10	theme	flight	1138:1143	arg1	MS					1174:1175	MALDI-TOF MS	1164:1175	MALDI-TOF MS	1164:1175	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	10	11	theme	isomeric	2090:2097	arg1	structures					2099:2108	isomeric structures	2090:2108	isomeric structures containing sialic acid epitopes	2090:2140	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	5	12	theme	human	854:858	arg1	body					860:863	the human body	850:863	the human body	850:863	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	7	13	theme	PGC-LC	1404:1409	arg1	MRM					1442:1444	MRM	1442:1444	MRM	1442:1444	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	13	theme	PGC-LC	1404:1409	arg1	monitoring					1430:1439	graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring	1362:1439	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	9	14	theme	N-glycan	1931:1938	arg1	terminus					1907:1914	the terminus	1903:1914	the terminus of biantennary N-glycan	1903:1938	In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD.
34888356	1	15	theme	chronic	189:195	arg1	vasculitis					220:229	chronic and relapsing systemic vasculitis	189:229	vasculitis	220:229	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34888356	7	16	theme	chromatography	1388:1401	arg1	MRM					1442:1444	MRM	1442:1444	MRM	1442:1444	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	16	theme	chromatography	1388:1401	arg1	monitoring					1430:1439	graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring	1362:1439	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	10	17	theme	acid	2128:2131	arg1	epitopes					2133:2140	sialic acid epitopes	2121:2140	sialic acid epitopes	2121:2140	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	1	18	theme	relapsing	201:209	arg1	vasculitis					220:229	chronic and relapsing systemic vasculitis	189:229	vasculitis	220:229	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34888356	7	19	theme	graphitized	1362:1372	arg1	MRM					1442:1444	MRM	1442:1444	MRM	1442:1444	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	19	theme	graphitized	1362:1372	arg1	monitoring					1430:1439	graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring	1362:1439	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	5	20	from	changes	816:822	arg1	epitope					839:845	sialic acid epitope	827:845	sialic acid epitope in the human body	827:863	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	5	21	theme	new	886:888	arg1	changes					816:822	changes	816:822	changes in sialic acid epitope in the human body	816:863	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	5	21	theme	new	886:888	arg1	indicator					890:898	a new indicator	884:898	a new indicator to monitor the onset and progression of immune diseases	884:954	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	9	22	from	terminus	1907:1914	arg1	epitope					1948:1954	the epitope	1944:1954	the epitope associated with BD	1944:1973	In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD.
34888356	9	22	from	terminus	1907:1914	arg1	acid					1895:1898	α2,3-sialic acid	1883:1898	α2,3-sialic acid at the terminus of biantennary N-glycan	1883:1938	In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD.
34888356	4	23	theme	glycoconjugates	688:702	arg1	terminus					676:683	the terminus	672:683	the terminus of glycoconjugates	672:702	In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell-cell/pathogen interactions, and tumor progression.
34888356	8	24	theme	0.945	1790:1794	arg1	AUC					1782:1784	AUC	1782:1784	AUC	1782:1784	Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers.
34888356	8	24	theme	0.945	1790:1794	arg1	curve					1775:1779	the curve	1771:1779	the curve (AUC) of 0.945	1771:1794	Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers.
34888356	5	25	dep	onset	915:919	arg1	the					911:913	the	911:913	the	911:913	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	0	26	theme	α2,3-Linked	74:84	arg1	Acid					93:96	α2,3-Linked Sialic Acid	74:96	α2,3-Linked Sialic Acid Epitope	74:104	Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.
34888356	3	27	theme	immunological	578:590	arg1	function					592:599	the immunological function	574:599	the immunological function of glycans	574:610	As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted.
34888356	5	28	from	epitope	839:845	arg1	body					860:863	the human body	850:863	the human body	850:863	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	11	29	theme	clinical	2210:2217	arg1	cohorts					2219:2225	large clinical cohorts	2204:2225	large clinical cohorts	2204:2225	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	0	30	theme	Acid	93:96	arg1	Epitope					98:104	α2,3-Linked Sialic Acid Epitope	74:104	α2,3-Linked Sialic Acid Epitope	74:104	Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.
34888356	2	31	with	marker	436:441	arg1	sensitivity					453:463	high sensitivity	448:463	high sensitivity	448:463	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	2	31	with	marker	436:441	arg1	specificity					474:484	high specificity	469:484	high specificity	469:484	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	8	32	theme	novel	1825:1829	arg1	biomarkers					1834:1843	novel BD biomarkers	1825:1843	novel BD biomarkers	1825:1843	Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers.
34888356	4	33	theme	cell-cell/pathogen	749:766	arg1	interactions					768:779	cell-cell/pathogen interactions	749:779	cell-cell/pathogen interactions	749:779	In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell-cell/pathogen interactions, and tumor progression.
34888356	2	34	theme	optimal	383:389	arg1	treatment					391:399	optimal treatment	383:399	optimal treatment of BD	383:405	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	5	35	theme	diseases	947:954	arg1	onset					915:919	onset	915:919	onset	915:919	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	5	35	theme	diseases	947:954	arg1	progression					925:935	progression	925:935	progression	925:935	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	7	36	theme	isomers	1322:1328	arg1	quantification					1334:1347	quantification	1334:1347	quantification	1334:1347	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	36	theme	isomers	1322:1328	arg1	separation					1300:1309	the separation	1296:1309	the separation of linkage isomers	1296:1328	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	2	37	dep	efforts	315:321	arg1	discover					326:333	discover	326:333	to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD	323:405	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	0	38	theme	Isomer-Specific	0:14	arg1	Monitoring					16:25	Isomer-Specific Monitoring	0:25	Isomer-Specific Monitoring of Sialylated N-Glycans	0:49	Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.
34888356	11	39	theme	glycan	2159:2164	arg1	profiling					2166:2174	Isomer-specific glycan profiling	2143:2174	Isomer-specific glycan profiling	2143:2174	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	7	40	from	compositions	1548:1559	arg1	epitopes					1517:1524	sialic acid epitopes	1505:1524	sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2	1505:1637	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	4	41	theme	sialic	656:661	arg1	acids					663:667	sialic acids	656:667	sialic acids at the terminus of glycoconjugates	656:702	In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell-cell/pathogen interactions, and tumor progression.
34888356	2	42	theme	high	448:451	arg1	sensitivity					453:463	high sensitivity	448:463	high sensitivity	448:463	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	0	43	theme	N-Glycans	41:49	arg1	Monitoring					16:25	Isomer-Specific Monitoring	0:25	Isomer-Specific Monitoring of Sialylated N-Glycans	0:49	Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.
34888356	1	44	theme	even	284:287	arg1	death					289:293	even death	284:293	even death	284:293	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34888356	6	45	theme	N-glycan	996:1003	arg1	compositions					1005:1016	N-glycan compositions	996:1016	N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients	996:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	7	46	theme	sialic	1505:1510	arg1	epitopes					1517:1524	sialic acid epitopes	1505:1524	sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2	1505:1637	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	8	47	with	control	1706:1712	arg1	specificity					1740:1750	specificity	1740:1750	specificity	1740:1750	Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers.
34888356	8	47	with	control	1706:1712	arg1	sensitivity					1724:1734	high sensitivity	1719:1734	high sensitivity	1719:1734	Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers.
34888356	1	48	theme	systemic	211:218	arg1	vasculitis					220:229	chronic and relapsing systemic vasculitis	189:229	vasculitis	220:229	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34888356	7	49	gly	sialylated	1237:1246	arg1	N-glycans					1260:1268	three sialylated biantennary N-glycans	1231:1268	three sialylated biantennary N-glycans	1231:1268	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	6	50	theme	BD	1068:1069	arg1	patients					1071:1078	47 BD patients	1065:1078	47 BD patients	1065:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	4	51	theme	tumor	786:790	arg1	progression					792:802	tumor progression	786:802	tumor progression	786:802	In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell-cell/pathogen interactions, and tumor progression.
34888356	1	52	theme	etiology	242:249	arg1	vasculitis					220:229	chronic and relapsing systemic vasculitis	189:229	vasculitis	220:229	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34888356	6	53	theme	healthy	1046:1052	arg1	donors					1054:1059	47 healthy donors	1043:1059	47 healthy donors	1043:1059	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	9	54	theme	α2,3-sialic	1883:1893	arg1	epitope					1948:1954	the epitope	1944:1954	the epitope associated with BD	1944:1973	In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD.
34888356	9	54	theme	α2,3-sialic	1883:1893	arg1	acid					1895:1898	α2,3-sialic acid	1883:1898	α2,3-sialic acid at the terminus of biantennary N-glycan	1883:1938	In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD.
34888356	7	55	theme	/multiple	1411:1419	arg1	MRM					1442:1444	MRM	1442:1444	MRM	1442:1444	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	55	theme	/multiple	1411:1419	arg1	monitoring					1430:1439	graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring	1362:1439	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	10	56	theme	sialic	2121:2126	arg1	epitopes					2133:2140	sialic acid epitopes	2121:2140	sialic acid epitopes	2121:2140	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	11	57	theme	assays	2277:2282	arg1	introduction					2250:2261	the introduction	2246:2261	the introduction of diagnostic assays for other immune diseases	2246:2308	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	11	58	theme	Isomer-specific	2143:2157	arg1	profiling					2166:2174	Isomer-specific glycan profiling	2143:2174	Isomer-specific glycan profiling	2143:2174	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	6	59	theme	mass	1145:1148	arg1	spectrometry					1150:1161	flight mass spectrometry	1138:1161	flight mass spectrometry (MALDI-TOF MS)	1138:1176	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	6	59	theme	mass	1145:1148	arg1	MS					1174:1175	MALDI-TOF MS	1164:1175	MALDI-TOF MS	1164:1175	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	11	60	theme	diagnostic	2266:2275	arg1	assays					2277:2282	diagnostic assays	2266:2282	diagnostic assays	2266:2282	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	7	61	theme	reaction	1421:1428	arg1	MRM					1442:1444	MRM	1442:1444	MRM	1442:1444	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	61	theme	reaction	1421:1428	arg1	monitoring					1430:1439	graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring	1362:1439	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	9	62	theme	biantennary	1919:1929	arg1	N-glycan					1931:1938	biantennary N-glycan	1919:1938	biantennary N-glycan	1919:1938	In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD.
34888356	3	63	theme	immune	529:534	arg1	system					536:541	the immune system	525:541	the immune system	525:541	As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted.
34888356	6	64	theme	laser	1102:1106	arg1	desorption/ionization-time					1108:1133	matrix-assisted laser desorption/ionization-time	1086:1133	matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS)	1086:1176	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	11	65	theme	immune	2294:2299	arg1	diseases					2301:2308	other immune diseases	2288:2308	other immune diseases	2288:2308	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	5	66	theme	sialic	827:832	arg1	acid					834:837	sialic acid	827:837	sialic acid epitope in the human body	827:863	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	6	67	theme	target	1209:1214	arg1	glycans					1216:1222	BD target glycans	1206:1222	BD target glycans	1206:1222	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	7	68	theme	carbon-liquid	1374:1386	arg1	MRM					1442:1444	MRM	1442:1444	MRM	1442:1444	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	68	theme	carbon-liquid	1374:1386	arg1	monitoring					1430:1439	graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring	1362:1439	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	69	theme	porous	1355:1360	arg1	-MS.					1446:1449	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS.	1355:1449	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	6	70	theme	patients	1071:1078	arg1	sera					1035:1038	the sera	1031:1038	the sera of 47 healthy donors and 47 BD patients	1031:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	0	71	theme	Sialic	86:91	arg1	Acid					93:96	α2,3-Linked Sialic Acid	74:96	α2,3-Linked Sialic Acid Epitope	74:104	Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.
34888356	6	72	theme	global	976:981	arg1	profiling					983:991	global profiling	976:991	global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients	976:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	2	73	theme	high	469:472	arg1	specificity					474:484	high specificity	469:484	high specificity	469:484	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	0	74	theme	Epitope	98:104	arg1	Association					59:69	Association	59:69	Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease	59:126	Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.
34888356	11	75	theme	cohorts	2219:2225	arg1	analysis					2192:2199	analysis	2192:2199	analysis of large clinical cohorts	2192:2225	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	7	76	theme	glycan	1541:1546	arg1	compositions					1548:1559	the three glycan compositions	1531:1559	the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2	1531:1637	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	4	77	theme	immune	731:736	arg1	responses					738:746	immune responses	731:746	immune responses	731:746	In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell-cell/pathogen interactions, and tumor progression.
34888356	7	78	theme	biantennary	1248:1258	arg1	N-glycans					1260:1268	three sialylated biantennary N-glycans	1231:1268	three sialylated biantennary N-glycans	1231:1268	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	5	79	theme	immune	940:945	arg1	diseases					947:954	immune diseases	940:954	immune diseases	940:954	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	7	80	theme	linkage	1314:1320	arg1	isomers					1322:1328	linkage isomers	1314:1328	linkage isomers	1314:1328	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	10	81	theme	novel	2004:2008	arg1	approach					2010:2017	a novel approach	2002:2017	a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes	2002:2140	In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes.
34888356	8	82	theme	BD	1831:1832	arg1	biomarkers					1834:1843	novel BD biomarkers	1825:1843	novel BD biomarkers	1825:1843	Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers.
34888356	2	83	theme	rapid	363:367	arg1	diagnosis					369:377	accurate and rapid diagnosis	350:377	accurate and rapid diagnosis	350:377	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	0	84	theme	Sialylated	30:39	arg1	N-Glycans					41:49	Sialylated N-Glycans	30:49	Sialylated N-Glycans	30:49	Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.
34888356	3	85	from	research	562:569	arg1	function					592:599	the immunological function	574:599	the immunological function of glycans	574:610	As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted.
34888356	2	86	theme	BD	404:405	arg1	diagnosis					369:377	accurate and rapid diagnosis	350:377	accurate and rapid diagnosis	350:377	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	2	86	theme	BD	404:405	arg1	treatment					391:399	optimal treatment	383:399	optimal treatment of BD	383:405	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	6	87	theme	compositions	1005:1016	arg1	profiling					983:991	global profiling	976:991	global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients	976:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	11	88	theme	large	2204:2208	arg1	cohorts					2219:2225	large clinical cohorts	2204:2225	large clinical cohorts	2204:2225	Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.
34888356	3	89	theme	glycans	604:610	arg1	function					592:599	the immunological function	574:599	the immunological function of glycans	574:610	As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted.
34888356	6	90	theme	matrix-assisted	1086:1100	arg1	desorption/ionization-time					1108:1133	matrix-assisted laser desorption/ionization-time	1086:1133	matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS)	1086:1176	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	2	91	theme	signature	426:434	arg1	marker					436:441	no signature marker	423:441	no signature marker with high sensitivity and high specificity	423:484	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	7	92	theme	acid	1512:1515	arg1	epitopes					1517:1524	sialic acid epitopes	1505:1524	sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2	1505:1637	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	7	93	theme	sialylated	1237:1246	arg1	N-glycans					1260:1268	three sialylated biantennary N-glycans	1231:1268	three sialylated biantennary N-glycans	1231:1268	Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2.
34888356	2	94	theme	continuous	304:313	arg1	efforts					315:321	continuous efforts	304:321	continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD	304:405	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	4	95	from	terminus	676:683	arg1	acids					663:667	sialic acids	656:667	sialic acids at the terminus of glycoconjugates	656:702	In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell-cell/pathogen interactions, and tumor progression.
34888356	5	96	theme	acid	834:837	arg1	epitope					839:845	sialic acid epitope	827:845	sialic acid epitope in the human body	827:863	Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases.
34888356	6	97	theme	spectrometry	1150:1161	arg1	desorption/ionization-time					1108:1133	matrix-assisted laser desorption/ionization-time	1086:1133	matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS)	1086:1176	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	6	98	attach	derived	1018:1024	arg1	sera					1035:1038	the sera	1031:1038	the sera of 47 healthy donors and 47 BD patients	1031:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	6	98	attach	derived	1018:1024	arg2	compositions					1005:1016	N-glycan compositions	996:1016	N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients	996:1078	Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans.
34888356	2	99	theme	accurate	350:357	arg1	diagnosis					369:377	accurate and rapid diagnosis	350:377	accurate and rapid diagnosis	350:377	Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity.
34888356	1	100	theme	unknown	234:240	arg1	etiology					242:249	unknown etiology	234:249	unknown etiology	234:249	Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death.
34019851	7	0	theme	substrate	1283:1291	arg1	complexes					1293:1301	similar acceptor substrate complexes	1266:1301	similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite	1266:1357	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	7	1	with	complexes	1293:1301	arg1	residue					1333:1339	the nonreducing glucosyl residue	1308:1339	the nonreducing glucosyl residue in the +1 subsite	1308:1357	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	6	2	theme	E441A	966:970	arg1	mutant					972:977	the TxGH116 E441A mutant	954:977	the TxGH116 E441A mutant with α-GlcF	954:989	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	4	3	theme	highest	645:651	arg1	activity					667:674	highest glycosynthase activity	645:674	highest glycosynthase activity	645:674	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	2	4	theme	hydrolase	325:333	arg1	families					340:347	glycoside hydrolase (GH) families	315:347	glycoside hydrolase (GH) families	315:347	Although glycosynthases have been characterized from a variety of glycoside hydrolase (GH) families, family GH116 glycosynthases have yet to be reported.
34019851	6	5	with	soaking	1035:1041	arg1	α-GlcF					1076:1081	α-GlcF	1076:1081	α-GlcF	1076:1081	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	4	6	contain	had	764:766	arg2	activity					788:795	low but significant activity	768:795	low but significant activity	768:795	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	4	6	contain	had	764:766	arg1	E441D					758:762	E441D	758:762	E441D	758:762	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	3	7	theme	E441A	585:589	arg1	mutant					591:596	the previously generated E441A mutant	560:596	the previously generated E441A mutant	560:596	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	7	8	with	Soaking	1204:1210	arg1	cellobiose					1235:1244	cellobiose	1235:1244	cellobiose	1235:1244	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	7	8	with	Soaking	1204:1210	arg1	cellotriose					1249:1259	cellotriose	1249:1259	cellotriose	1249:1259	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	4	9	theme	cellobiose	731:740	arg1	acceptor					742:749	cellobiose acceptor	731:749	cellobiose acceptor	731:749	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	2	10	theme	families	340:347	arg1	families					340:347	glycoside hydrolase (GH) families	315:347	glycoside hydrolase (GH) families	315:347	Although glycosynthases have been characterized from a variety of glycoside hydrolase (GH) families, family GH116 glycosynthases have yet to be reported.
34019851	2	10	theme	families	340:347	arg1	variety					304:310	a variety	302:310	a variety of glycoside hydrolase (GH) families	302:347	Although glycosynthases have been characterized from a variety of glycoside hydrolase (GH) families, family GH116 glycosynthases have yet to be reported.
34019851	2	11	theme	GH	336:337	arg1	families					340:347	glycoside hydrolase (GH) families	315:347	glycoside hydrolase (GH) families	315:347	Although glycosynthases have been characterized from a variety of glycoside hydrolase (GH) families, family GH116 glycosynthases have yet to be reported.
34019851	8	12	theme	apparent	1665:1672	arg1	preference					1674:1683	its apparent preference	1661:1683	its apparent preference for production of β-1,4-linked oligosaccharides	1661:1731	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	5	13	theme	p-nitrophenyl	902:914	arg1	acceptors					926:934	p-nitrophenyl glycoside acceptors	902:934	p-nitrophenyl glycoside acceptors	902:934	The E441G, E441S and E441A variants showed broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors.
34019851	6	14	theme	donor	1004:1008	arg1	complex					1020:1026	the donor substrate complex	1000:1026	the donor substrate complex	1000:1026	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	8	15	theme	plausible	1497:1505	arg1	structure					1507:1515	a plausible structure	1495:1515	a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides	1495:1731	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	4	16	theme	low	768:770	arg1	activity					788:795	low but significant activity	768:795	low but significant activity	768:795	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	4	17	theme	significant	776:786	arg1	activity					788:795	low but significant activity	768:795	low but significant activity	768:795	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	9	18	theme	glycosynthases	1831:1844	arg1	development					1810:1820	development	1810:1820	development of GH116 glycosynthases	1810:1844	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	8	19	theme	catalytic	1524:1532	arg1	complex					1542:1548	the catalytic ternary complex	1520:1548	the catalytic ternary complex	1520:1548	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	7	20	theme	acceptor	1274:1281	arg1	complexes					1293:1301	similar acceptor substrate complexes	1266:1301	similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite	1266:1357	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	6	21	theme	mutant	1064:1069	arg1	soaking					1035:1041	soaking	1035:1041	soaking of the TxGH116 E441G mutant with α-GlcF	1035:1081	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	8	22	theme	complex	1542:1548	arg1	structure					1507:1515	a plausible structure	1495:1515	a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides	1495:1731	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	6	23	theme	TxGH116	1050:1056	arg1	mutant					1064:1069	the TxGH116 E441G mutant	1046:1069	the TxGH116 E441G mutant	1046:1069	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	9	24	theme	oligosaccharides	1863:1878	arg1	synthesis					1850:1858	synthesis	1850:1858	synthesis of oligosaccharides and glycosides of interest	1850:1905	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	9	25	theme	glycosides	1884:1893	arg1	synthesis					1850:1858	synthesis	1850:1858	synthesis of oligosaccharides and glycosides of interest	1850:1905	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	3	26	dep	Thermoanaerobacterium	419:439	arg1	xylanolyticum					441:453	xylanolyticum	441:453	xylanolyticum	441:453	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	9	27	theme	interest	1898:1905	arg1	glycosides					1884:1893	glycosides	1884:1893	glycosides	1884:1893	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	9	27	theme	interest	1898:1905	arg1	oligosaccharides					1863:1878	oligosaccharides	1863:1878	oligosaccharides	1863:1878	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	8	28	theme	glucosyl	1580:1587	arg1	2.5 Å					1600:1604	the nonreducing glucosyl residue O4 2.5 Å	1564:1604	the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF	1564:1639	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	0	29	theme	Structural	0:9	arg1	basis					11:15	Structural basis	0:15	Structural basis for transglycosylation in glycoside hydrolase family GH116	0:74	Structural basis for transglycosylation in glycoside hydrolase family GH116 glycosynthases.
34019851	1	30	theme	glycoside	111:119	arg1	Glycosynthases					92:105	Glycosynthases	92:105	Glycosynthases	92:105	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	1	30	theme	glycoside	111:119	arg1	mutants					131:137	glycoside hydrolase mutants	111:137	glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products	111:246	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	8	31	theme	O4	1597:1598	arg1	2.5 Å					1600:1604	the nonreducing glucosyl residue O4 2.5 Å	1564:1604	the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF	1564:1639	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	5	32	theme	α-glycosyl	871:880	arg1	donors					891:896	α-glycosyl fluoride donors	871:896	α-glycosyl fluoride donors	871:896	The E441G, E441S and E441A variants showed broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors.
34019851	3	33	theme	generated	575:583	arg1	mutant					591:596	the previously generated E441A mutant	560:596	the previously generated E441A mutant	560:596	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	34	theme	TxGH116	455:461	arg1	E441Q					497:501	E441Q	497:501	E441Q	497:501	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	34	theme	TxGH116	455:461	arg1	mutants					475:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants	415:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S	415:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	34	theme	TxGH116	455:461	arg1	E441G					490:494	E441G	490:494	E441G	490:494	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	34	theme	TxGH116	455:461	arg1	E441S					507:511	E441S	507:511	E441S	507:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	4	35	theme	E441G	611:615	arg1	mutants					627:633	The TxGH116 E441G and E441S mutants	599:633	The TxGH116 E441G and E441S mutants	599:633	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	1	36	theme	inverted	198:205	arg1	donor					207:211	an inverted donor	195:211	an inverted donor	195:211	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	3	37	theme	Thermoanaerobacterium	419:439	arg1	E441Q					497:501	E441Q	497:501	E441Q	497:501	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	37	theme	Thermoanaerobacterium	419:439	arg1	mutants					475:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants	415:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S	415:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	37	theme	Thermoanaerobacterium	419:439	arg1	E441G					490:494	E441G	490:494	E441G	490:494	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	37	theme	Thermoanaerobacterium	419:439	arg1	E441S					507:511	E441S	507:511	E441S	507:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	8	38	theme	anomeric	1615:1622	arg1	carbon					1624:1629	the anomeric carbon	1611:1629	the anomeric carbon of α-GlcF	1611:1639	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	0	39	theme	hydrolase	53:61	arg1	family					63:68	glycoside hydrolase family GH116	43:74	glycoside hydrolase family GH116	43:74	Structural basis for transglycosylation in glycoside hydrolase family GH116 glycosynthases.
34019851	6	40	from	glycerol	1176:1183	arg1	subsite					1195:1201	the -1 subsite	1188:1201	the -1 subsite	1188:1201	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	2	41	theme	GH116	357:361	arg1	glycosynthases					363:376	family GH116 glycosynthases	350:376	family GH116 glycosynthases	350:376	Although glycosynthases have been characterized from a variety of glycoside hydrolase (GH) families, family GH116 glycosynthases have yet to be reported.
34019851	7	42	theme	glucosyl	1324:1331	arg1	residue					1333:1339	the nonreducing glucosyl residue	1308:1339	the nonreducing glucosyl residue in the +1 subsite	1308:1357	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	4	43	theme	glycosynthase	653:665	arg1	activity					667:674	highest glycosynthase activity	645:674	highest glycosynthase activity	645:674	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	8	44	theme	oligosaccharides	1716:1731	arg1	production					1689:1698	production	1689:1698	production of β-1,4-linked oligosaccharides	1689:1731	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	6	45	theme	active	1158:1163	arg1	site					1165:1168	the active site	1154:1168	the active site	1154:1168	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	6	46	theme	mutant	972:977	arg1	structure					941:949	The structure	937:949	The structure of the TxGH116 E441A mutant with α-GlcF	937:989	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	4	47	theme	E441S	621:625	arg1	mutants					627:633	The TxGH116 E441G and E441S mutants	599:633	The TxGH116 E441G and E441S mutants	599:633	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	8	48	from	E441A	1415:1419	arg1	ligands					1390:1396	the ligands	1386:1396	the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose	1386:1484	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	6	49	theme	TxGH116	958:964	arg1	mutant					972:977	the TxGH116 E441A mutant	954:977	the TxGH116 E441A mutant with α-GlcF	954:989	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	2	50	theme	glycoside	315:323	arg1	families					340:347	glycoside hydrolase (GH) families	315:347	glycoside hydrolase (GH) families	315:347	Although glycosynthases have been characterized from a variety of glycoside hydrolase (GH) families, family GH116 glycosynthases have yet to be reported.
34019851	5	51	theme	glycoside	916:924	arg1	acceptors					926:934	p-nitrophenyl glycoside acceptors	902:934	p-nitrophenyl glycoside acceptors	902:934	The E441G, E441S and E441A variants showed broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors.
34019851	9	52	theme	functional	1739:1748	arg1	characterization					1765:1780	This functional and structural characterization	1734:1780	This functional and structural characterization	1734:1780	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	8	53	from	carbon	1624:1629	arg1	2.5 Å					1600:1604	the nonreducing glucosyl residue O4 2.5 Å	1564:1604	the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF	1564:1639	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	9	54	theme	structural	1754:1763	arg1	characterization					1765:1780	This functional and structural characterization	1734:1780	This functional and structural characterization	1734:1780	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	7	55	from	residue	1333:1339	arg1	subsite					1351:1357	the +1 subsite	1344:1357	the +1 subsite	1344:1357	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	4	56	from	α-fluoroglucoside	701:717	arg1	glucose					688:694	transfer glucose	679:694	transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor	679:749	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	5	57	theme	fluoride	882:889	arg1	donors					891:896	α-glycosyl fluoride donors	871:896	α-glycosyl fluoride donors	871:896	The E441G, E441S and E441A variants showed broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors.
34019851	5	58	dep	E441S	817:821	arg1	variants					833:840	variants	833:840	variants	833:840	The E441G, E441S and E441A variants showed broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors.
34019851	5	58	dep	E441S	817:821	arg1	The					806:808	The	806:808	The	806:808	The E441G, E441S and E441A variants showed broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors.
34019851	1	59	theme	products	239:246	arg1	hydrolysis					221:230	hydrolysis	221:230	hydrolysis of the products	221:246	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	6	60	theme	substrate	1010:1018	arg1	complex					1020:1026	the donor substrate complex	1000:1026	the donor substrate complex	1000:1026	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	9	61	theme	GH116	1825:1829	arg1	glycosynthases					1831:1844	GH116 glycosynthases	1825:1844	GH116 glycosynthases	1825:1844	This functional and structural characterization provides the background for development of GH116 glycosynthases for synthesis of oligosaccharides and glycosides of interest.
34019851	8	62	theme	ternary	1534:1540	arg1	complex					1542:1548	the catalytic ternary complex	1520:1548	the catalytic ternary complex	1520:1548	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	7	63	theme	similar	1266:1272	arg1	complexes					1293:1301	similar acceptor substrate complexes	1266:1301	similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite	1266:1357	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	1	64	from	donor	207:211	arg1	glycosides					179:188	glycosides	179:188	glycosides	179:188	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	1	64	from	donor	207:211	arg1	oligosaccharides					159:174	oligosaccharides	159:174	oligosaccharides	159:174	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	6	65	theme	E441G	1058:1062	arg1	mutant					1064:1069	the TxGH116 E441G mutant	1046:1069	the TxGH116 E441G mutant	1046:1069	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	0	66	from	basis	11:15	arg1	family					63:68	glycoside hydrolase family GH116	43:74	glycoside hydrolase family GH116	43:74	Structural basis for transglycosylation in glycoside hydrolase family GH116 glycosynthases.
34019851	8	67	link	β-1,4-linked	1703:1714	arg1	oligosaccharides					1716:1731	β-1,4-linked oligosaccharides	1703:1731	β-1,4-linked oligosaccharides	1703:1731	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	8	68	theme	nonreducing	1568:1578	arg1	2.5 Å					1600:1604	the nonreducing glucosyl residue O4 2.5 Å	1564:1604	the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF	1564:1639	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	7	69	theme	E441G	1224:1228	arg1	Soaking					1204:1210	Soaking	1204:1210	Soaking of E441A or E441G with cellobiose or cellotriose	1204:1259	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	8	70	theme	residue	1589:1595	arg1	2.5 Å					1600:1604	the nonreducing glucosyl residue O4 2.5 Å	1564:1604	the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF	1564:1639	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	5	71	theme	broad	849:853	arg1	specificity					855:865	broad specificity	849:865	broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors	849:934	The E441G, E441S and E441A variants showed broad specificity for α-glycosyl fluoride donors and p-nitrophenyl glycoside acceptors.
34019851	6	72	theme	+1	1136:1137	arg1	subsite					1139:1145	the +1 subsite	1132:1145	the +1 subsite out of the active site	1132:1168	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	1	73	theme	hydrolase	121:129	arg1	Glycosynthases					92:105	Glycosynthases	92:105	Glycosynthases	92:105	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	1	73	theme	hydrolase	121:129	arg1	mutants					131:137	glycoside hydrolase mutants	111:137	glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products	111:246	Glycosynthases are glycoside hydrolase mutants that can synthesize oligosaccharides or glycosides from an inverted donor without hydrolysis of the products.
34019851	8	74	theme	α-GlcF	1426:1431	arg1	crystals					1433:1440	α-GlcF crystals	1426:1440	α-GlcF crystals	1426:1440	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	0	75	theme	glycoside	43:51	arg1	family					63:68	glycoside hydrolase family GH116	43:74	glycoside hydrolase family GH116	43:74	Structural basis for transglycosylation in glycoside hydrolase family GH116 glycosynthases.
34019851	3	76	dep	mutants	475:481	arg1	E441Q					497:501	E441Q	497:501	E441Q	497:501	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	76	dep	mutants	475:481	arg1	mutants					475:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants	415:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S	415:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	76	dep	mutants	475:481	arg1	E441G					490:494	E441G	490:494	E441G	490:494	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	76	dep	mutants	475:481	arg1	E441S					507:511	E441S	507:511	E441S	507:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	77	theme	nucleophile	463:473	arg1	E441Q					497:501	E441Q	497:501	E441Q	497:501	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	77	theme	nucleophile	463:473	arg1	mutants					475:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants	415:481	the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S	415:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	77	theme	nucleophile	463:473	arg1	E441G					490:494	E441G	490:494	E441G	490:494	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	3	77	theme	nucleophile	463:473	arg1	E441S					507:511	E441S	507:511	E441S	507:511	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	6	78	with	mutant	972:977	arg1	α-GlcF					984:989	α-GlcF	984:989	α-GlcF	984:989	The structure of the TxGH116 E441A mutant with α-GlcF provided the donor substrate complex, while soaking of the TxGH116 E441G mutant with α-GlcF resulted in cellooligosaccharides extending from the +1 subsite out of the active site, with glycerol in the -1 subsite.
34019851	8	79	theme	α-GlcF	1634:1639	arg1	carbon					1624:1629	the anomeric carbon	1611:1629	the anomeric carbon of α-GlcF	1611:1639	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	3	80	theme	glycosynthase	532:544	arg1	activities					546:555	their glycosynthase activities	526:555	their glycosynthase activities	526:555	We produced the Thermoanaerobacterium xylanolyticum TxGH116 nucleophile mutants E441D, E441G, E441Q and E441S and compared their glycosynthase activities to the previously generated E441A mutant.
34019851	8	81	theme	β-1,4-linked	1703:1714	arg1	oligosaccharides					1716:1731	β-1,4-linked oligosaccharides	1703:1731	β-1,4-linked oligosaccharides	1703:1731	Combining structures with the ligands from the TxGH116 E441A with α-GlcF crystals with that of E441A or E441G with cellobiose provides a plausible structure of the catalytic ternary complex, which places the nonreducing glucosyl residue O4 2.5 Å from the anomeric carbon of α-GlcF, thereby explaining its apparent preference for production of β-1,4-linked oligosaccharides.
34019851	7	82	theme	nonreducing	1312:1322	arg1	residue					1333:1339	the nonreducing glucosyl residue	1308:1339	the nonreducing glucosyl residue in the +1 subsite	1308:1357	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34019851	2	83	theme	family	350:355	arg1	glycosynthases					363:376	family GH116 glycosynthases	350:376	family GH116 glycosynthases	350:376	Although glycosynthases have been characterized from a variety of glycoside hydrolase (GH) families, family GH116 glycosynthases have yet to be reported.
34019851	4	84	theme	transfer	679:686	arg1	glucose					688:694	transfer glucose	679:694	transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor	679:749	The TxGH116 E441G and E441S mutants exhibited highest glycosynthase activity to transfer glucose from α-fluoroglucoside (α-GlcF) to cellobiose acceptor, while E441D had low but significant activity as well.
34019851	7	85	theme	E441A	1215:1219	arg1	Soaking					1204:1210	Soaking	1204:1210	Soaking of E441A or E441G with cellobiose or cellotriose	1204:1259	Soaking of E441A or E441G with cellobiose or cellotriose gave similar acceptor substrate complexes with the nonreducing glucosyl residue in the +1 subsite.
34768939	5	0	theme	receptor	646:653	arg1	glycosylation					620:632	glycosylation	620:632	glycosylation of the ACE2 receptor	620:653	We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity.
34768939	1	1	theme	severe	151:156	arg1	infection					158:166	severe infection	151:166	severe infection by the SARS-CoV-2 virus	151:190	Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females.
34768939	4	2	theme	ACE2	582:585	arg1	receptor					587:594	the human ACE2 receptor	572:594	the human ACE2 receptor	572:594	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	0	3	theme	Cell	77:80	arg1	Entry					82:86	SARS-CoV-2 Cell Entry	66:86	SARS-CoV-2 Cell Entry	66:86	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.
34768939	8	4	theme	sex	1055:1057	arg1	hormones					1059:1066	female sex hormones	1048:1066	female sex hormones	1048:1066	These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
34768939	7	5	gly	glycosylation	916:928	arg1	model					874:878	a mouse model	866:878	a mouse model of COVID-19	866:890	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
34768939	4	6	theme	human	576:580	arg1	receptor					587:594	the human ACE2 receptor	572:594	the human ACE2 receptor	572:594	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	3	7	theme	female	363:368	arg1	hormones					374:381	female sex hormones	363:381	female sex hormones	363:381	However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown.
34768939	7	8	theme	spike	976:980	arg1	protein					982:988	the SARS-CoV-2 spike protein	961:988	the SARS-CoV-2 spike protein	961:988	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
34768939	5	9	theme	SARS-CoV-2	664:673	arg1	infectivity					675:685	SARS-CoV-2 infectivity	664:685	SARS-CoV-2 infectivity	664:685	We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity.
34768939	3	10	theme	sex	370:372	arg1	hormones					374:381	female sex hormones	363:381	female sex hormones	363:381	However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown.
34768939	4	11	theme	molecular	491:499	arg1	basis					501:505	the molecular basis	487:505	the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor	487:594	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	7	12	theme	protein	982:988	arg1	uptake					951:956	alveolar uptake	942:956	alveolar uptake of the SARS-CoV-2 spike protein	942:988	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
34768939	7	13	theme	COVID-19	883:890	arg1	model					874:878	a mouse model	866:878	a mouse model of COVID-19	866:890	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
34768939	8	14	theme	putative	1021:1028	arg1	mechanism					1030:1038	a putative mechanism	1019:1038	a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19	1019:1192	These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
34768939	6	15	theme	glycan-glycan	723:735	arg1	interactions					737:748	glycan-glycan interactions	723:748	glycan-glycan interactions	723:748	Importantly, estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells.
34768939	0	16	theme	Sex	45:47	arg1	Hormones					49:56	Female Sex Hormones	38:56	Female Sex Hormones against SARS-CoV-2 Cell Entry	38:86	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.
34768939	7	17	theme	SARS-CoV-2	965:974	arg1	protein					982:988	the SARS-CoV-2 spike protein	961:988	the SARS-CoV-2 spike protein	961:988	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
34768939	8	18	theme	severe	1107:1112	arg1	infection					1114:1122	severe infection	1107:1122	severe infection	1107:1122	These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
34768939	0	19	theme	SARS-CoV-2	66:75	arg1	Entry					82:86	SARS-CoV-2 Cell Entry	66:86	SARS-CoV-2 Cell Entry	66:86	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.
34768939	1	20	theme	SARS-CoV-2	175:184	arg1	virus					186:190	the SARS-CoV-2 virus	171:190	the SARS-CoV-2 virus	171:190	Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females.
34768939	0	21	theme	Structural	0:9	arg1	Analysis					26:33	Structural and Functional Analysis	0:33	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.	0:87	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.
34768939	5	22	theme	ACE2	641:644	arg1	receptor					646:653	the ACE2 receptor	637:653	the ACE2 receptor	637:653	We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity.
34768939	8	23	theme	female	1048:1053	arg1	hormones					1059:1066	female sex hormones	1048:1066	female sex hormones	1048:1066	These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
34768939	1	24	theme	Emerging	89:96	arg1	evidence					98:105	Emerging evidence	89:105	Emerging evidence	89:105	Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females.
34768939	7	25	theme	mouse	868:872	arg1	model					874:878	a mouse model	866:878	a mouse model of COVID-19	866:890	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
34768939	0	26	theme	Functional	15:24	arg1	Analysis					26:33	Structural and Functional Analysis	0:33	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.	0:87	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.
34768939	4	27	theme	new	469:471	arg1	insights					473:480	new insights	469:480	new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor	469:594	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	2	28	theme	sex	308:310	arg1	hormones					312:319	sex hormones	308:319	sex hormones	308:319	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	5	29	gly	glycosylation	620:632	arg1	receptor					646:653	the ACE2 receptor	637:653	the ACE2 receptor	637:653	We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity.
34768939	0	30	theme	Female	38:43	arg1	Hormones					49:56	Female Sex Hormones	38:56	Female Sex Hormones against SARS-CoV-2 Cell Entry	38:86	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.
34768939	4	31	theme	spike	550:554	arg1	protein					560:566	the SARS-CoV-2 spike (S) protein	535:566	the SARS-CoV-2 spike (S) protein	535:566	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	2	32	theme	mechanisms	219:228	arg1	mechanisms					219:228	mechanisms	219:228	mechanisms	219:228	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	2	32	theme	mechanisms	219:228	arg1	variety					208:214	A variety	206:214	A variety of mechanisms	206:228	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	0	33	theme	Hormones	49:56	arg1	Analysis					26:33	Structural and Functional Analysis	0:33	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.	0:87	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry.
34768939	4	34	theme	SARS-CoV-2	539:548	arg1	protein					560:566	the SARS-CoV-2 spike (S) protein	535:566	the SARS-CoV-2 spike (S) protein	535:566	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	3	35	theme	SARS-CoV-2	414:423	arg1	infectivity					425:435	SARS-CoV-2 infectivity	414:435	SARS-CoV-2 infectivity	414:435	However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown.
34768939	4	36	theme	S	557:557	arg1	protein					560:566	the SARS-CoV-2 spike (S) protein	535:566	the SARS-CoV-2 spike (S) protein	535:566	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	6	37	theme	human	794:798	arg1	ACE2					800:803	the human ACE2	790:803	the human ACE2	790:803	Importantly, estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells.
34768939	7	38	theme	alveolar	942:949	arg1	uptake					951:956	alveolar uptake	942:956	alveolar uptake of the SARS-CoV-2 spike protein	942:988	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
34768939	8	39	theme	future	1160:1165	arg1	therapies					1167:1175	future therapies	1160:1175	future therapies against COVID-19	1160:1192	These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
34768939	2	40	theme	gender-related	256:269	arg1	differences					293:303	differences	293:303	differences in sex hormones	293:319	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	2	40	theme	gender-related	256:269	arg1	disparities					271:281	the observed gender-related disparities	243:281	the observed gender-related disparities including differences in sex hormones	243:319	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	2	41	theme	observed	247:254	arg1	differences					293:303	differences	293:303	differences in sex hormones	293:319	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	2	41	theme	observed	247:254	arg1	disparities					271:281	the observed gender-related disparities	243:281	the observed gender-related disparities including differences in sex hormones	243:319	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	3	42	theme	precise	335:341	arg1	mechanisms					343:352	the precise mechanisms	331:352	the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity	331:435	However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown.
34768939	2	43	from	differences	293:303	arg1	hormones					312:319	sex hormones	308:319	sex hormones	308:319	A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones.
34768939	8	44	theme	therapies	1167:1175	arg1	development					1145:1155	the development	1141:1155	the development of future therapies against COVID-19	1141:1192	These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
34768939	4	45	theme	interactions	514:525	arg1	basis					501:505	the molecular basis	487:505	the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor	487:594	Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor.
34768939	6	46	theme	glycan-protein	754:767	arg1	interactions					769:780	glycan-protein interactions	754:780	glycan-protein interactions	754:780	Importantly, estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells.
34768939	7	47	theme	ACE2	911:914	arg1	glycosylation					916:928	ACE2 glycosylation	911:928	ACE2 glycosylation	911:928	In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein.
33004438	7	0	theme	site	1274:1277	arg1	mutants					1279:1285	FUT8 active site mutants	1262:1285	FUT8 active site mutants	1262:1285	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	5	1	dep	structures	856:865	arg1	identify					961:968	identify	961:968	identify the molecular basis for FUT8 specificity and activity	961:1022	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	2	2	theme	glycan	333:338	arg1	core					340:343	the glycan core	329:343	the glycan core	329:343	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	9	3	theme	fold	1735:1738	arg1	glycosyltransferases					1740:1759	GT-B fold glycosyltransferases	1730:1759	GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems	1730:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	3	4	theme	mice	574:577	arg1	phenotypes					550:559	the complex pathological phenotypes	525:559	the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality	525:670	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	1	5	theme	secretory	212:220	arg1	pathway					222:228	the secretory pathway	208:228	the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins	208:299	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33004438	0	6	theme	structural	79:88	arg1	similarities					90:101	structural similarities	79:101	structural similarities with related fucosyltransferases	79:134	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	4	7	gly	fucosylation	687:698	arg1	cancers					742:748	several human cancers	728:748	several human cancers	728:748	Elevated core fucosylation has also been identified in several human cancers.
33004438	3	8	theme	cellular	605:612	arg1	signaling					614:622	cellular signaling	605:622	cellular signaling	605:622	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	4	9	theme	Elevated	673:680	arg1	fucosylation					687:698	Elevated core fucosylation	673:698	Elevated core fucosylation	673:698	Elevated core fucosylation has also been identified in several human cancers.
33004438	1	10	theme	diverse	242:248	arg1	glycans					250:256	diverse glycans	242:256	diverse glycans	242:256	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33004438	9	11	from	glycosyltransferases	1740:1759	arg1	synthesis					1768:1776	the synthesis	1764:1776	the synthesis of diverse glycan structures in biological systems	1764:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	9	12	theme	diverse	1781:1787	arg1	structures					1796:1805	diverse glycan structures	1781:1805	diverse glycan structures	1781:1805	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	5	13	theme	donor	893:897	arg1	analog					909:914	a donor substrate analog	891:914	a donor substrate analog	891:914	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	9	14	theme	structures	1796:1805	arg1	synthesis					1768:1776	the synthesis	1764:1776	the synthesis of diverse glycan structures in biological systems	1764:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	8	15	theme	known	1489:1493	arg1	fucosyltransferases					1495:1513	other known fucosyltransferases	1483:1513	other known fucosyltransferases	1483:1513	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	9	16	theme	biological	1810:1819	arg1	systems					1821:1827	biological systems	1810:1827	biological systems	1810:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	3	17	from	defects	594:600	arg1	development					625:635	development	625:635	development	625:635	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	3	17	from	defects	594:600	arg1	signaling					614:622	cellular signaling	605:622	cellular signaling	605:622	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	3	17	from	defects	594:600	arg1	lethality					662:670	subsequent neonatal lethality	642:670	subsequent neonatal lethality	642:670	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	2	18	theme	Additional	302:311	arg1	modification					313:324	Additional modification	302:324	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation)	302:420	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	6	19	theme	site	1054:1057	arg1	loops					1059:1063	three active site loops	1041:1063	three active site loops	1041:1063	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	8	20	theme	conserved	1527:1535	arg1	features					1562:1569	conserved and divergent structural features	1527:1569	conserved and divergent structural features for donor and acceptor recognition and catalysis	1527:1618	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	7	21	theme	site	1370:1373	arg1	complementarity					1375:1389	binding site complementarity	1362:1389	binding site complementarity	1362:1389	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	6	22	theme	increased	1083:1091	arg1	occupancy					1093:1101	an increased occupancy	1080:1101	an increased occupancy for bound GDP	1080:1115	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	4	23	theme	several	728:734	arg1	cancers					742:748	several human cancers	728:748	several human cancers	728:748	Elevated core fucosylation has also been identified in several human cancers.
33004438	7	24	theme	active	1267:1272	arg1	mutants					1279:1285	FUT8 active site mutants	1262:1285	FUT8 active site mutants	1262:1285	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	0	25	theme	α-1,6-fucosyltransferase	21:44	arg1	specificity					63:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	8	26	theme	divergent	1541:1549	arg1	features					1562:1569	conserved and divergent structural features	1527:1569	conserved and divergent structural features for donor and acceptor recognition and catalysis	1527:1618	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	5	27	theme	glycan	940:945	arg1	acceptors					947:955	four distinct glycan acceptors	926:955	four distinct glycan acceptors	926:955	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	0	28	theme	related	108:114	arg1	fucosyltransferases					116:134	related fucosyltransferases	108:134	related fucosyltransferases	108:134	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	8	29	theme	donor	1575:1579	arg1	recognition					1594:1604	donor and acceptor recognition	1575:1604	donor and acceptor recognition	1575:1604	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	5	30	theme	FUT8	785:788	arg1	specificity					800:810	FUT8 substrate specificity	785:810	FUT8 substrate specificity	785:810	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	7	31	theme	binding	1362:1368	arg1	complementarity					1375:1389	binding site complementarity	1362:1389	binding site complementarity	1362:1389	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	8	32	theme	acceptor	1585:1592	arg1	recognition					1594:1604	donor and acceptor recognition	1575:1604	donor and acceptor recognition	1575:1604	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	7	33	theme	FUT8	1262:1265	arg1	mutants					1279:1285	FUT8 active site mutants	1262:1285	FUT8 active site mutants	1262:1285	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	7	34	theme	complexes	1217:1225	arg1	Structures					1182:1191	Structures	1182:1191	Structures of the various acceptor complexes	1182:1225	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	5	35	theme	molecular	974:982	arg1	basis					984:988	the molecular basis	970:988	the molecular basis for FUT8 specificity and activity	970:1022	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	7	36	theme	various	1200:1206	arg1	complexes					1217:1225	the various acceptor complexes	1196:1225	the various acceptor complexes	1196:1225	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	1	37	theme	Mammalian	137:145	arg1	glycans					158:164	Mammalian Asn-linked glycans	137:164	Mammalian Asn-linked glycans	137:164	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33004438	7	38	theme	acceptors	1338:1346	arg1	library					1320:1326	a library	1318:1326	a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity	1318:1438	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	5	39	with	complex	878:884	arg1	analog					909:914	a donor substrate analog	891:914	a donor substrate analog	891:914	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	5	39	with	complex	878:884	arg1	acceptors					947:955	four distinct glycan acceptors	926:955	four distinct glycan acceptors	926:955	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	3	40	theme	core	492:495	arg1	fucosylation					497:508	core fucosylation	492:508	core fucosylation	492:508	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	0	41	theme	FUT8	47:50	arg1	specificity					63:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	7	42	from	library	1320:1326	arg1	data					1308:1311	specificity data	1296:1311	specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity	1296:1438	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	8	43	theme	FUT8	1445:1448	arg1	structure					1450:1458	The FUT8 structure	1441:1458	The FUT8 structure	1441:1458	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	5	44	theme	crystal	848:854	arg1	structures					856:865	various crystal structures	840:865	various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity	840:1022	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	9	45	theme	modular	1671:1677	arg1	templates					1679:1687	modular templates	1671:1687	modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems	1671:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	3	46	theme	subsequent	642:651	arg1	lethality					662:670	subsequent neonatal lethality	642:670	subsequent neonatal lethality	642:670	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	1	47	link	Asn-linked	147:156	arg1	glycans					158:164	Mammalian Asn-linked glycans	137:164	Mammalian Asn-linked glycans	137:164	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33004438	2	48	theme	innermost	377:385	arg1	residue					394:400	the innermost GlcNAc residue	373:400	the innermost GlcNAc residue (core fucosylation)	373:420	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	2	48	theme	innermost	377:385	arg1	fucosylation					408:419	core fucosylation	403:419	core fucosylation	403:419	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	1	49	theme	cell	261:264	arg1	surface					266:272	cell surface	261:272	cell surface	261:272	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33004438	2	50	theme	core	403:406	arg1	residue					394:400	the innermost GlcNAc residue	373:400	the innermost GlcNAc residue (core fucosylation)	373:420	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	2	50	theme	core	403:406	arg1	fucosylation					408:419	core fucosylation	403:419	core fucosylation	403:419	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	0	51	with	similarities	90:101	arg1	fucosyltransferases					116:134	related fucosyltransferases	108:134	related fucosyltransferases	108:134	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	2	52	theme	core	340:343	arg1	modification					313:324	Additional modification	302:324	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation)	302:420	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	9	53	theme	GT-B	1730:1733	arg1	glycosyltransferases					1740:1759	GT-B fold glycosyltransferases	1730:1759	GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems	1730:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	3	54	theme	null	569:572	arg1	mice					574:577	FUT8 null mice	564:577	FUT8 null mice	564:577	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	5	55	theme	substrate	899:907	arg1	analog					909:914	a donor substrate analog	891:914	a donor substrate analog	891:914	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	0	56	theme	substrate	53:61	arg1	specificity					63:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	2	57	theme	α-1,6-fucose	348:359	arg1	addition					361:368	α-1,6-fucose addition	348:368	α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation)	348:420	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	8	58	theme	other	1483:1487	arg1	fucosyltransferases					1495:1513	other known fucosyltransferases	1483:1513	other known fucosyltransferases	1483:1513	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	6	59	theme	subsite	1173:1179	arg1	folding					1144:1150	an induced-fit folding	1129:1150	an induced-fit folding of the donor-binding subsite	1129:1179	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	3	60	theme	pathological	537:548	arg1	phenotypes					550:559	the complex pathological phenotypes	525:559	the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality	525:670	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	2	61	theme	GlcNAc	387:392	arg1	residue					394:400	the innermost GlcNAc residue	373:400	the innermost GlcNAc residue (core fucosylation)	373:420	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	2	61	theme	GlcNAc	387:392	arg1	fucosylation					408:419	core fucosylation	403:419	core fucosylation	403:419	Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8).
33004438	9	62	theme	glycan	1789:1794	arg1	structures					1796:1805	diverse glycan structures	1781:1805	diverse glycan structures	1781:1805	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	7	63	theme	substrate	1421:1429	arg1	affinity					1431:1438	substrate affinity	1421:1438	substrate affinity	1421:1438	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	4	64	theme	core	682:685	arg1	fucosylation					687:698	Elevated core fucosylation	673:698	Elevated core fucosylation	673:698	Elevated core fucosylation has also been identified in several human cancers.
33004438	1	65	theme	Asn-linked	147:156	arg1	glycans					158:164	Mammalian Asn-linked glycans	137:164	Mammalian Asn-linked glycans	137:164	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33004438	7	66	from	data	1254:1257	arg1	mutants					1279:1285	FUT8 active site mutants	1262:1285	FUT8 active site mutants	1262:1285	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	3	67	theme	neonatal	653:660	arg1	lethality					662:670	subsequent neonatal lethality	642:670	subsequent neonatal lethality	642:670	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	6	68	theme	loops	1059:1063	arg1	ordering					1029:1036	The ordering	1025:1036	The ordering of three active site loops	1025:1063	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	7	69	theme	steric	1395:1400	arg1	hindrance					1402:1410	steric hindrance	1395:1410	steric hindrance	1395:1410	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	5	70	theme	substrate	790:798	arg1	specificity					800:810	FUT8 substrate specificity	785:810	FUT8 substrate specificity	785:810	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	9	71	dep	donor	1693:1697	arg1	recognition					1712:1722	recognition	1712:1722	recognition	1712:1722	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	6	72	theme	active	1047:1052	arg1	loops					1059:1063	three active site loops	1041:1063	three active site loops	1041:1063	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	8	73	theme	structural	1551:1560	arg1	features					1562:1569	conserved and divergent structural features	1527:1569	conserved and divergent structural features for donor and acceptor recognition and catalysis	1527:1618	The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis.
33004438	7	74	theme	kinetic	1246:1252	arg1	data					1254:1257	kinetic data	1246:1257	kinetic data on FUT8 active site mutants	1246:1285	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	5	75	theme	distinct	931:938	arg1	acceptors					947:955	four distinct glycan acceptors	926:955	four distinct glycan acceptors	926:955	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	4	76	theme	human	736:740	arg1	cancers					742:748	several human cancers	728:748	several human cancers	728:748	Elevated core fucosylation has also been identified in several human cancers.
33004438	5	77	theme	structural	764:773	arg1	basis					775:779	the structural basis	760:779	the structural basis for FUT8 substrate specificity	760:810	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	5	78	theme	FUT8	994:997	arg1	specificity					999:1009	FUT8 specificity	994:1009	FUT8 specificity	994:1009	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	9	79	from	synthesis	1768:1776	arg1	systems					1821:1827	biological systems	1810:1827	biological systems	1810:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	0	80	theme	human	15:19	arg1	specificity					63:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	human α-1,6-fucosyltransferase (FUT8) substrate specificity	15:73	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	1	81	gly	glycoproteins	287:299	arg1	glycoproteins					287:299	secreted glycoproteins	278:299	secreted glycoproteins	278:299	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33004438	5	82	theme	FUT8	870:873	arg1	structures					856:865	various crystal structures	840:865	various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity	840:1022	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	7	83	theme	glycan	1331:1336	arg1	acceptors					1338:1346	glycan acceptors	1331:1346	glycan acceptors	1331:1346	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	3	84	theme	fucosylation	497:508	arg1	importance					478:487	The importance	474:487	The importance of core fucosylation	474:508	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	5	85	theme	various	840:846	arg1	structures					856:865	various crystal structures	840:865	various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity	840:1022	However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity.
33004438	6	86	theme	donor-binding	1159:1171	arg1	subsite					1173:1179	the donor-binding subsite	1155:1179	the donor-binding subsite	1155:1179	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	3	87	theme	complex	529:535	arg1	phenotypes					550:559	the complex pathological phenotypes	525:559	the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality	525:670	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	9	88	theme	templates	1679:1687	arg1	evolution					1658:1666	the evolution	1654:1666	the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems	1654:1827	These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
33004438	7	89	theme	specificity	1296:1306	arg1	data					1308:1311	specificity data	1296:1311	specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity	1296:1438	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	0	90	with	specificity	63:73	arg1	fucosyltransferases					116:134	related fucosyltransferases	108:134	related fucosyltransferases	108:134	Characterizing human α-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.
33004438	3	91	theme	FUT8	564:567	arg1	mice					574:577	FUT8 null mice	564:577	FUT8 null mice	564:577	The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality.
33004438	6	92	theme	induced-fit	1132:1142	arg1	folding					1144:1150	an induced-fit folding	1129:1150	an induced-fit folding of the donor-binding subsite	1129:1179	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	6	93	theme	bound	1107:1111	arg1	GDP					1113:1115	bound GDP	1107:1115	bound GDP	1107:1115	The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite.
33004438	7	94	theme	acceptor	1208:1215	arg1	complexes					1217:1225	the various acceptor complexes	1196:1225	the various acceptor complexes	1196:1225	Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity.
33004438	1	95	theme	secreted	278:285	arg1	glycoproteins					287:299	secreted glycoproteins	278:299	secreted glycoproteins	278:299	Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins.
33139572	4	0	theme	prefrontal	901:910	arg1	PFC					920:922	PFC	920:922	PFC	920:922	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	4	0	theme	prefrontal	901:910	arg1	cortex					912:917	the prefrontal cortex	897:917	the prefrontal cortex (PFC)	897:923	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	2	1	theme	brain	591:595	arg1	functions					597:605	brain functions	591:605	brain functions	591:605	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	2	2	theme	spatial	335:341	arg1	analysis					356:363	spatial and temporal analysis	335:363	spatial and temporal analysis of glycome expression patterns in the mammalian brain	335:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	1	3	theme	inherent	236:243	arg1	complexity					245:254	the inherent complexity	232:254	the inherent complexity	232:254	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	6	4	theme	unique	1191:1196	arg1	glycans					1183:1189	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans	1086:1189	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain	1086:1209	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified.
33139572	3	5	theme	brain	749:753	arg1	regions					755:761	nine different brain regions	734:761	nine different brain regions in mouse	734:770	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	6	6	theme	Novel	1177:1181	arg1	glycans					1183:1189	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans	1086:1189	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain	1086:1209	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified.
33139572	9	7	theme	new	1708:1710	arg1	studies					1712:1718	new studies	1708:1718	new studies exploring the role of glycans in spatiotemporally diverse brain functions	1708:1792	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	3	8	from	regions	755:761	arg1	mouse					766:770	mouse	766:770	mouse	766:770	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	2	9	theme	valuable	539:546	arg1	implications					548:559	valuable implications	539:559	valuable implications	539:559	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	9	10	theme	glycans	1742:1748	arg1	role					1734:1737	the role	1730:1737	the role of glycans in spatiotemporally diverse brain functions	1730:1792	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	4	11	theme	different	928:936	arg1	point					943:947	different time point	928:947	different time point across six postnatal stages in mouse	928:984	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	3	12	theme	apparent	639:646	arg1	diversity					648:656	an apparent diversity	636:656	an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse	636:770	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	9	13	theme	brain	1778:1782	arg1	functions					1784:1792	spatiotemporally diverse brain functions	1753:1792	spatiotemporally diverse brain functions	1753:1792	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	0	14	theme	mammalian	56:64	arg1	brain					66:70	mammalian brain	56:70	mammalian brain	56:70	Spatial and temporal diversity of glycome expression in mammalian brain.
33139572	8	15	theme	glycan	1519:1524	arg1	diversity					1526:1534	the glycan diversity	1515:1534	the glycan diversity during the PFC development	1515:1561	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	2	16	theme	molecular	564:572	arg1	events					574:579	molecular events	564:579	molecular events regarding brain functions and development	564:621	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	1	17	theme	large-scale	159:169	arg1	studies					179:185	other large-scale "omics" studies	153:185	other large-scale "omics" studies	153:185	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	1	17	theme	large-scale	159:169	arg1	transcriptomics					209:223	transcriptomics	209:223	transcriptomics	209:223	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	1	17	theme	large-scale	159:169	arg1	genomics					196:203	genomics	196:203	genomics	196:203	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	2	18	theme	ultimate	517:524	arg1	aim					526:528	the ultimate aim	513:528	the ultimate aim	513:528	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	8	19	theme	PFC	1547:1549	arg1	development					1551:1561	the PFC development	1543:1561	the PFC development	1543:1561	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	2	20	theme	patterns	387:394	arg1	analysis					356:363	spatial and temporal analysis	335:363	spatial and temporal analysis of glycome expression patterns in the mammalian brain	335:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	1	21	theme	Mammalian	73:81	arg1	glycome					89:95	Mammalian brain glycome	73:95	Mammalian brain glycome	73:95	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	2	22	theme	experimental	440:451	arg1	tool					453:456	a cutting-edge experimental tool	425:456	a cutting-edge experimental tool	425:456	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	8	23	theme	vast	1387:1390	arg1	heterogeneity					1392:1404	the vast heterogeneity	1383:1404	the vast heterogeneity of glycans	1383:1415	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	2	24	theme	glycome	368:374	arg1	patterns					387:394	glycome expression patterns	368:394	glycome expression patterns in the mammalian brain	368:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	0	25	theme	Spatial	0:6	arg1	diversity					21:29	Spatial and temporal diversity	0:29	Spatial and temporal diversity of glycome expression in mammalian brain	0:70	Spatial and temporal diversity of glycome expression in mammalian brain.
33139572	9	26	theme	diversity	1599:1607	arg1	levels					1589:1594	high levels	1584:1594	high levels of diversity in a glycosylation program underlying brain region specificity and age dependency	1584:1689	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	7	27	theme	PFC	1348:1350	arg1	development					1352:1362	PFC development	1348:1362	PFC development	1348:1362	Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development.
33139572	0	28	theme	temporal	12:19	arg1	diversity					21:29	Spatial and temporal diversity	0:29	Spatial and temporal diversity of glycome expression in mammalian brain	0:70	Spatial and temporal diversity of glycome expression in mammalian brain.
33139572	1	29	theme	glycan	277:282	arg1	structure					284:292	glycan structure	277:292	glycan structure	277:292	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	2	30	theme	liquid	467:472	arg1	spectrometry					494:505	liquid chromatography-mass spectrometry	467:505	liquid chromatography-mass spectrometry	467:505	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	3	31	theme	glycome	665:671	arg1	well-preserved					713:726	well-preserved	713:726	well-preserved	713:726	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	3	31	theme	glycome	665:671	arg1	patterns					684:691	the glycome expression patterns	661:691	the glycome expression patterns	661:691	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	4	32	theme	postnatal	856:864	arg1	development					872:882	postnatal brain development	856:882	postnatal brain development	856:882	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	0	33	theme	expression	42:51	arg1	diversity					21:29	Spatial and temporal diversity	0:29	Spatial and temporal diversity of glycome expression in mammalian brain	0:70	Spatial and temporal diversity of glycome expression in mammalian brain.
33139572	8	34	gly	heterogeneity	1392:1404	arg1	glycans					1409:1415	glycans	1409:1415	glycans	1409:1415	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	5	35	theme	postnatal	1062:1070	arg1	developments					1072:1083	postnatal developments	1062:1083	postnatal developments	1062:1083	We found that glycan expression profiles were dynamically regulated during postnatal developments.
33139572	2	36	from	patterns	387:394	arg1	brain					413:417	the mammalian brain	399:417	the mammalian brain	399:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	7	37	theme	fucosylated	1295:1305	arg1	glycans					1307:1313	fucosylated glycans	1295:1313	fucosylated glycans	1295:1313	Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development.
33139572	8	38	theme	core	1435:1438	arg1	map					1456:1458	a core glyco-synthesis map	1433:1458	a core glyco-synthesis map	1433:1458	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	5	39	theme	expression	1008:1017	arg1	profiles					1019:1026	glycan expression profiles	1001:1026	glycan expression profiles	1001:1026	We found that glycan expression profiles were dynamically regulated during postnatal developments.
33139572	1	40	theme	due	225:227	arg1	genomics					196:203	genomics	196:203	genomics	196:203	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	9	41	theme	age	1676:1678	arg1	dependency					1680:1689	age dependency	1676:1689	age dependency	1676:1689	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	2	42	from	brain	413:417	arg1	analysis					356:363	spatial and temporal analysis	335:363	spatial and temporal analysis of glycome expression patterns in the mammalian brain	335:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	6	43	theme	PFC	1119:1121	arg1	samples					1123:1129	PFC samples	1119:1129	PFC samples from humans ranging in age from 39 d to 49 y.	1119:1175	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified.
33139572	3	44	from	diversity	648:656	arg1	well-preserved					713:726	well-preserved	713:726	well-preserved	713:726	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	3	44	from	diversity	648:656	arg1	patterns					684:691	the glycome expression patterns	661:691	the glycome expression patterns	661:691	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	4	45	from	stages	970:975	arg1	mouse					980:984	mouse	980:984	mouse	980:984	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	4	46	theme	brain	866:870	arg1	development					872:882	postnatal brain development	856:882	postnatal brain development	856:882	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	3	47	theme	different	739:747	arg1	regions					755:761	nine different brain regions	734:761	nine different brain regions in mouse	734:770	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	2	48	from	analysis	356:363	arg1	brain					413:417	the mammalian brain	399:417	the mammalian brain	399:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	9	49	theme	brain	1647:1651	arg1	specificity					1660:1670	brain region specificity	1647:1670	brain region specificity	1647:1670	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	4	50	theme	time	938:941	arg1	point					943:947	different time point	928:947	different time point across six postnatal stages in mouse	928:984	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	6	51	dep	y.	1174:1175	arg1	to					1168:1169	to	1168:1169	to	1168:1169	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified.
33139572	8	52	theme	glycosylation	1477:1489	arg1	pathway					1491:1497	the glycosylation pathway	1473:1497	the glycosylation pathway responsible for the glycan diversity during the PFC development	1473:1561	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	6	53	dep	glycans	1183:1189	arg1	obtained					1107:1114	obtained	1107:1114	was obtained in PFC samples from humans ranging in age from 39 d to 49 y.	1103:1175	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified.
33139572	1	54	gly	heterogeneity	260:272	arg1	properties					298:307	properties	298:307	properties	298:307	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	1	54	gly	heterogeneity	260:272	arg1	structure					284:292	glycan structure	277:292	glycan structure	277:292	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	8	55	theme	responsible	1499:1509	arg1	pathway					1491:1497	the glycosylation pathway	1473:1497	the glycosylation pathway responsible for the glycan diversity during the PFC development	1473:1561	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	5	56	theme	glycan	1001:1006	arg1	profiles					1019:1026	glycan expression profiles	1001:1026	glycan expression profiles	1001:1026	We found that glycan expression profiles were dynamically regulated during postnatal developments.
33139572	1	57	theme	understood	125:134	arg1	area					136:139	a relatively poorly understood area	105:139	a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties	105:307	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	9	58	theme	diverse	1770:1776	arg1	functions					1784:1792	spatiotemporally diverse brain functions	1753:1792	spatiotemporally diverse brain functions	1753:1792	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	4	59	theme	glycome	803:809	arg1	pattern					822:828	the glycome expression pattern	799:828	the glycome expression pattern	799:828	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	9	60	from	diversity	1599:1607	arg1	program					1628:1634	a glycosylation program	1612:1634	a glycosylation program underlying brain region specificity and age dependency	1612:1689	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	0	61	from	diversity	21:29	arg1	brain					66:70	mammalian brain	56:70	mammalian brain	56:70	Spatial and temporal diversity of glycome expression in mammalian brain.
33139572	1	62	theme	other	153:157	arg1	studies					179:185	other large-scale "omics" studies	153:185	other large-scale "omics" studies	153:185	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	1	62	theme	other	153:157	arg1	transcriptomics					209:223	transcriptomics	209:223	transcriptomics	209:223	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	1	62	theme	other	153:157	arg1	genomics					196:203	genomics	196:203	genomics	196:203	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	9	63	from	levels	1589:1594	arg1	program					1628:1634	a glycosylation program	1612:1634	a glycosylation program underlying brain region specificity and age dependency	1612:1689	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	9	64	from	role	1734:1737	arg1	functions					1784:1792	spatiotemporally diverse brain functions	1753:1792	spatiotemporally diverse brain functions	1753:1792	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	2	65	theme	chromatography-mass	474:492	arg1	spectrometry					494:505	liquid chromatography-mass spectrometry	467:505	liquid chromatography-mass spectrometry	467:505	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	4	66	theme	postnatal	960:968	arg1	stages					970:975	six postnatal stages	956:975	six postnatal stages in mouse	956:984	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	9	67	theme	high	1584:1587	arg1	levels					1589:1594	high levels	1584:1594	high levels of diversity in a glycosylation program underlying brain region specificity and age dependency	1584:1689	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	2	68	theme	expression	376:385	arg1	patterns					387:394	glycome expression patterns	368:394	glycome expression patterns in the mammalian brain	368:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	1	69	theme	brain	83:87	arg1	glycome					89:95	Mammalian brain glycome	73:95	Mammalian brain glycome	73:95	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	2	70	theme	cutting-edge	427:438	arg1	tool					453:456	a cutting-edge experimental tool	425:456	a cutting-edge experimental tool	425:456	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	1	71	dep	large-scale	159:169	arg1	"					177:177	"	177:177	"	177:177	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	6	72	theme	similar	1088:1094	arg1	result					1096:1101	A similar result	1086:1101	A similar result	1086:1101	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified.
33139572	2	73	theme	mammalian	403:411	arg1	brain					413:417	the mammalian brain	399:417	the mammalian brain	399:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
33139572	0	74	theme	glycome	34:40	arg1	expression					42:51	glycome expression	34:51	glycome expression	34:51	Spatial and temporal diversity of glycome expression in mammalian brain.
33139572	1	75	theme	structure	284:292	arg1	heterogeneity					260:272	heterogeneity	260:272	heterogeneity	260:272	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	1	75	theme	structure	284:292	arg1	complexity					245:254	the inherent complexity	232:254	the inherent complexity	232:254	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	9	76	theme	glycosylation	1614:1626	arg1	program					1628:1634	a glycosylation program	1612:1634	a glycosylation program underlying brain region specificity and age dependency	1612:1689	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	9	77	from	program	1628:1634	arg1	levels					1589:1594	high levels	1584:1594	high levels of diversity in a glycosylation program underlying brain region specificity and age dependency	1584:1689	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	8	78	theme	glycans	1409:1415	arg1	heterogeneity					1392:1404	the vast heterogeneity	1383:1404	the vast heterogeneity of glycans	1383:1415	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	1	79	theme	properties	298:307	arg1	heterogeneity					260:272	heterogeneity	260:272	heterogeneity	260:272	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	1	79	theme	properties	298:307	arg1	complexity					245:254	the inherent complexity	232:254	the inherent complexity	232:254	Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties.
33139572	7	80	gly	fucosylated	1295:1305	arg1	glycans					1307:1313	fucosylated glycans	1295:1313	fucosylated glycans	1295:1313	Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development.
33139572	4	81	theme	expression	811:820	arg1	pattern					822:828	the glycome expression pattern	799:828	the glycome expression pattern	799:828	Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse.
33139572	9	82	theme	region	1653:1658	arg1	specificity					1660:1670	brain region specificity	1647:1670	brain region specificity	1647:1670	Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
33139572	3	83	theme	expression	673:682	arg1	well-preserved					713:726	well-preserved	713:726	well-preserved	713:726	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	3	83	theme	expression	673:682	arg1	patterns					684:691	the glycome expression patterns	661:691	the glycome expression patterns	661:691	We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse.
33139572	8	84	theme	glyco-synthesis	1440:1454	arg1	map					1456:1458	a core glyco-synthesis map	1433:1458	a core glyco-synthesis map	1433:1458	Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development.
33139572	6	85	from	humans	1136:1141	arg1	samples					1123:1129	PFC samples	1119:1129	PFC samples from humans ranging in age from 39 d to 49 y.	1119:1175	A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified.
33139572	2	86	theme	temporal	347:354	arg1	analysis					356:363	spatial and temporal analysis	335:363	spatial and temporal analysis of glycome expression patterns in the mammalian brain	335:417	Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development.
35140700	8	0	theme	carbohydrate	1111:1122	arg1	structures					1124:1133	The fine carbohydrate structures	1102:1133	The fine carbohydrate structures of IgG	1102:1140	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	4	1	theme	regulatory	588:597	arg1	effects					599:605	the regulatory effects	584:605	the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells	584:685	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	11	2	theme	IFN-γ	1674:1678	arg1	p<0.05					1693:1698	p<0.05	1693:1698	p<0.05	1693:1698	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	11	2	theme	IFN-γ	1674:1678	arg1	stimulation					1680:1690	IFN-γ stimulation	1674:1690	IFN-γ stimulation (p<0.05)	1674:1699	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	3	3	from	cytokines	508:516	arg1	effects					473:479	the effects	469:479	the effects of disturbances in various cytokines on IgG glycosylation	469:537	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	6	4	theme	enzyme-linked	904:916	arg1	immunoassay					918:928	enzyme-linked immunoassay	904:928	enzyme-linked immunoassay (ELISA)	904:936	Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation.
35140700	6	4	theme	enzyme-linked	904:916	arg1	ELISA					931:935	ELISA	931:935	ELISA	931:935	Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation.
35140700	11	5	dep	increased	1733:1741	arg1	p<0.05					1764:1769	p<0.05	1764:1769	p<0.05	1764:1769	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	13	6	gly	mono-sialylated	2045:2059	arg1	N-glycans					2078:2086	mono-sialylated and disialylated N-glycans	2045:2086	mono-sialylated and disialylated N-glycans	2045:2086	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	8	7	theme	spectrometry	1244:1255	arg1	trap-time					1219:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time	1160:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS)	1160:1270	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	13	8	theme	α-2,6-sialyltransferase	2201:2223	arg1	expression					2173:2182	the expression	2169:2182	the expression of β-galactoside α-2,6-sialyltransferase 1	2169:2225	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	9	9	with	stimulation	1355:1365	arg1	cytokines					1380:1388	several cytokines	1372:1388	several cytokines	1372:1388	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	12	10	theme	β-1,4-galactosyltransferase	1994:2020	arg1	upregulation					1978:1989	upregulation	1978:1989	upregulation of β-1,4-galactosyltransferase 1	1978:2022	The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of β-1,4-galactosyltransferase 1.
35140700	10	11	theme	glycan	1559:1564	arg1	patterns					1566:1573	considerably different IgG glycan patterns	1532:1573	considerably different IgG glycan patterns	1532:1573	Results We found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns.
35140700	8	12	theme	laser	1176:1180	arg1	trap-time					1219:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time	1160:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS)	1160:1270	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	4	13	theme	intracellular	640:652	arg1	glycosylation					658:670	intracellular IgG glycosylation	640:670	intracellular IgG glycosylation within B cells	640:685	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	2	14	theme	critical	290:297	arg1	role					299:302	a critical role	288:302	a critical role	288:302	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	8	15	theme	ion	1215:1217	arg1	trap-time					1219:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time	1160:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS)	1160:1270	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	5	16	theme	primary	731:737	arg1	system					747:752	a controlled primary culture system	718:752	a controlled primary culture system	718:752	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	1	17	theme	autoimmune	221:230	arg1	AIDs					242:245	AIDs	242:245	AIDs	242:245	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	1	17	theme	autoimmune	221:230	arg1	diseases					232:239	various autoimmune diseases	213:239	various autoimmune diseases (AIDs)	213:246	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	6	18	dep	IFN-γ	944:948	arg1	stimulation					988:998	stimulation	988:998	stimulation	988:998	Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation.
35140700	7	19	theme	glycosylation	1011:1023	arg1	levels					1025:1030	the glycosylation levels	1007:1030	the glycosylation levels of IgG under different stimuli	1007:1061	Next, the glycosylation levels of IgG under different stimuli were compared via a lectin microarray.
35140700	13	20	theme	asialylation	2151:2162	arg1	frequency					2138:2146	decreased frequency	2128:2146	decreased frequency of asialylation	2128:2162	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	2	21	theme	glycosylation	253:265	arg1	patterns					267:274	The glycosylation patterns	249:274	The glycosylation patterns of IgG	249:281	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	14	22	dep	Conclusion	2264:2273	arg1	cytokines					2295:2303	Abnormally elevated cytokines	2275:2303	Conclusion Abnormally elevated cytokines in the microenvironment	2264:2327	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	11	23	gly	sialylation	1710:1720	arg1	IgG					1725:1727	IgG	1725:1727	IgG	1725:1727	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	14	24	theme	B	2417:2417	arg1	cells					2419:2423	human B cells	2411:2423	human B cells	2411:2423	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	5	25	theme	CD19+	786:790	arg1	cells					794:798	human CD19+ B cells	780:798	human CD19+ B cells	780:798	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	13	26	theme	decreased	2128:2136	arg1	frequency					2138:2146	decreased frequency	2128:2146	decreased frequency of asialylation	2128:2162	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	1	27	theme	novel	169:173	arg1	feature					188:194	a novel pathological feature	167:194	a novel pathological feature	167:194	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	0	28	from	Cytokines	0:8	arg1	Microenvironment					24:39	the Immune Microenvironment	13:39	the Immune Microenvironment	13:39	Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases.
35140700	0	29	theme	Intracellular	87:99	arg1	Glycosyltransferases					101:120	Intracellular Glycosyltransferases	87:120	Intracellular Glycosyltransferases	87:120	Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases.
35140700	14	30	theme	intracellular	2373:2385	arg1	glycosyltransferases					2387:2406	intracellular glycosyltransferases	2373:2406	intracellular glycosyltransferases	2373:2406	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	3	31	theme	intracellular	422:434	arg1	mechanisms					447:456	the intracellular regulatory mechanisms	418:456	the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation	418:537	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	0	32	theme	IgG	69:71	arg1	Glycosylation					52:64	the Glycosylation	48:64	the Glycosylation of IgG	48:71	Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases.
35140700	12	33	theme	mono-galactosylation	1896:1915	arg1	frequency					1883:1891	the increased frequency	1869:1891	the increased frequency of mono-galactosylation	1869:1915	The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of β-1,4-galactosyltransferase 1.
35140700	1	34	from	Changes	134:140	arg1	glycosylation					149:161	IgG glycosylation	145:161	IgG glycosylation	145:161	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	14	35	theme	glycan	2343:2348	arg1	patterns					2350:2357	IgG glycan patterns	2339:2357	IgG glycan patterns	2339:2357	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	1	36	theme	Background	123:132	arg1	Changes					134:140	Background Changes	123:140	Background Changes	123:140	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	2	37	theme	AIDs	403:406	arg1	pathophysiology					379:393	the pathophysiology	375:393	the pathophysiology of many AIDs	375:406	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	4	38	theme	B	679:679	arg1	cells					681:685	B cells	679:685	B cells	679:685	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	9	39	theme	several	1372:1378	arg1	cytokines					1380:1388	several cytokines	1372:1388	several cytokines	1372:1388	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	10	40	theme	IgG	1555:1557	arg1	patterns					1566:1573	considerably different IgG glycan patterns	1532:1573	considerably different IgG glycan patterns	1532:1573	Results We found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns.
35140700	13	41	theme	disialylated	2065:2076	arg1	N-glycans					2078:2086	mono-sialylated and disialylated N-glycans	2045:2086	mono-sialylated and disialylated N-glycans	2045:2086	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	5	42	theme	antibody-secreting	805:822	arg1	ASCs					831:834	ASCs	831:834	ASCs	831:834	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	5	42	theme	antibody-secreting	805:822	arg1	cells					824:828	antibody-secreting cells	805:828	antibody-secreting cells (ASCs)	805:835	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	12	43	theme	agalactosylation	1824:1839	arg1	frequency					1811:1819	the frequency	1807:1819	the frequency of agalactosylation	1807:1839	The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of β-1,4-galactosyltransferase 1.
35140700	3	44	from	effects	473:479	arg1	cytokines					508:516	various cytokines	500:516	various cytokines	500:516	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	3	44	from	effects	473:479	arg1	glycosylation					525:537	IgG glycosylation	521:537	IgG glycosylation	521:537	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	2	45	theme	biological	322:331	arg1	function					333:340	biological function	322:340	biological function	322:340	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	12	46	theme	MALDI-TOF-MS	1777:1788	arg1	data					1790:1793	The MALDI-TOF-MS data	1773:1793	The MALDI-TOF-MS data	1773:1793	The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of β-1,4-galactosyltransferase 1.
35140700	4	47	theme	elevated	610:617	arg1	cytokines					619:627	elevated cytokines	610:627	elevated cytokines in AIDs	610:635	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	11	48	theme	IgG	1725:1727	arg1	sialylation					1710:1720	the sialylation	1706:1720	the sialylation of IgG	1706:1727	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	11	49	theme	IgG	1653:1655	arg1	level					1644:1648	the galactose level	1630:1648	the galactose level of IgG	1630:1655	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	3	50	theme	IgG	521:523	arg1	glycosylation					525:537	IgG glycosylation	521:537	IgG glycosylation	521:537	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	0	51	gly	Glycosylation	52:64	arg1	IgG					69:71	IgG	69:71	IgG	69:71	Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases.
35140700	2	52	gly	glycosylation	253:265	arg1	IgG					279:281	IgG	279:281	IgG	279:281	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	5	53	theme	human	780:784	arg1	cells					794:798	human CD19+ B cells	780:798	human CD19+ B cells	780:798	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	7	54	theme	lectin	1083:1088	arg1	microarray					1090:1099	a lectin microarray	1081:1099	a lectin microarray	1081:1099	Next, the glycosylation levels of IgG under different stimuli were compared via a lectin microarray.
35140700	13	55	theme	mono-sialylated	2045:2059	arg1	N-glycans					2078:2086	mono-sialylated and disialylated N-glycans	2045:2086	mono-sialylated and disialylated N-glycans	2045:2086	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	9	56	theme	western	1424:1430	arg1	blotting					1432:1439	western blotting	1424:1439	western blotting	1424:1439	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	8	57	theme	fine	1106:1109	arg1	structures					1124:1133	The fine carbohydrate structures	1102:1133	The fine carbohydrate structures of IgG	1102:1140	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	14	58	theme	elevated	2286:2293	arg1	cytokines					2295:2303	Abnormally elevated cytokines	2275:2303	Conclusion Abnormally elevated cytokines in the microenvironment	2264:2327	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	2	59	theme	IgG	279:281	arg1	patterns					267:274	The glycosylation patterns	249:274	The glycosylation patterns of IgG	249:281	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	1	60	theme	pathological	175:186	arg1	feature					188:194	a novel pathological feature	167:194	a novel pathological feature	167:194	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	8	61	theme	IgG	1138:1140	arg1	structures					1124:1133	The fine carbohydrate structures	1102:1133	The fine carbohydrate structures of IgG	1102:1140	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	11	62	dep	showed	1623:1628	arg1	increased					1661:1669	increased	1661:1669	showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05)	1623:1699	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	8	63	theme	flight-mass	1232:1242	arg1	MALDI-TOF-MS					1258:1269	MALDI-TOF-MS	1258:1269	MALDI-TOF-MS	1258:1269	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	8	63	theme	flight-mass	1232:1242	arg1	spectrometry					1244:1255	flight-mass spectrometry	1232:1255	flight-mass spectrometry (MALDI-TOF-MS)	1232:1270	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	6	64	from	concentrations	852:865	arg1	supernatants					874:885	the supernatants	870:885	the supernatants	870:885	Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation.
35140700	7	65	theme	different	1045:1053	arg1	stimuli					1055:1061	different stimuli	1045:1061	different stimuli	1045:1061	Next, the glycosylation levels of IgG under different stimuli were compared via a lectin microarray.
35140700	3	66	from	disturbances	484:495	arg1	cytokines					508:516	various cytokines	500:516	various cytokines	500:516	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	7	67	theme	IgG	1035:1037	arg1	levels					1025:1030	the glycosylation levels	1007:1030	the glycosylation levels of IgG under different stimuli	1007:1061	Next, the glycosylation levels of IgG under different stimuli were compared via a lectin microarray.
35140700	8	68	theme	matrix-assisted	1160:1174	arg1	trap-time					1219:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time	1160:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS)	1160:1270	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	13	69	theme	N-glycans	2078:2086	arg1	frequencies					2030:2040	Both frequencies	2025:2040	Both frequencies of mono-sialylated and disialylated N-glycans	2025:2086	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	5	70	theme	controlled	720:729	arg1	system					747:752	a controlled primary culture system	718:752	a controlled primary culture system	718:752	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	1	71	theme	various	213:219	arg1	AIDs					242:245	AIDs	242:245	AIDs	242:245	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	1	71	theme	various	213:219	arg1	diseases					232:239	various autoimmune diseases	213:239	various autoimmune diseases (AIDs)	213:246	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	8	72	theme	desorption/ionization-quadrupole	1182:1213	arg1	trap-time					1219:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time	1160:1227	matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS)	1160:1270	The fine carbohydrate structures of IgG were confirmed by matrix-assisted laser desorption/ionization-quadrupole ion trap-time of flight-mass spectrometry (MALDI-TOF-MS).
35140700	4	73	theme	IgG	654:656	arg1	glycosylation					658:670	intracellular IgG glycosylation	640:670	intracellular IgG glycosylation within B cells	640:685	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	13	74	theme	β-galactoside	2187:2199	arg1	α-2,6-sialyltransferase					2201:2223	β-galactoside α-2,6-sialyltransferase 1	2187:2225	β-galactoside α-2,6-sialyltransferase 1	2187:2225	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	9	75	from	expression	1286:1295	arg1	cells					1343:1347	B cells	1341:1347	B cells under stimulation with several cytokines	1341:1388	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	1	76	located	observed	201:208	arg1	AIDs					242:245	AIDs	242:245	AIDs	242:245	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	1	76	located	observed	201:208	arg2	Changes					134:140	Background Changes	123:140	Background Changes	123:140	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	1	76	located	observed	201:208	arg1	diseases					232:239	various autoimmune diseases	213:239	various autoimmune diseases (AIDs)	213:246	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	1	77	theme	IgG	145:147	arg1	glycosylation					149:161	IgG glycosylation	145:161	IgG glycosylation	145:161	Background Changes in IgG glycosylation, as a novel pathological feature, are observed in various autoimmune diseases (AIDs).
35140700	11	78	theme	microarray	1612:1621	arg1	results					1594:1600	the results	1590:1600	the results of lectin microarray	1590:1621	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	4	79	from	AIDs	632:635	arg1	effects					599:605	the regulatory effects	584:605	the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells	584:685	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	4	80	from	effects	599:605	arg1	glycosylation					658:670	intracellular IgG glycosylation	640:670	intracellular IgG glycosylation within B cells	640:685	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	4	80	from	effects	599:605	arg1	AIDs					632:635	AIDs	632:635	AIDs	632:635	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	4	81	from	cytokines	619:627	arg1	AIDs					632:635	AIDs	632:635	AIDs	632:635	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	14	82	from	Conclusion	2264:2273	arg1	microenvironment					2312:2327	the microenvironment	2308:2327	the microenvironment	2308:2327	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	14	83	theme	human	2411:2415	arg1	cells					2419:2423	human B cells	2411:2423	human B cells	2411:2423	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	5	84	theme	culture	739:745	arg1	system					747:752	a controlled primary culture system	718:752	a controlled primary culture system	718:752	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	9	85	theme	glycosyltransferases	1300:1319	arg1	expression					1286:1295	the expression	1282:1295	the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines	1282:1388	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	12	86	theme	digalactosylation	1944:1960	arg1	frequency					1931:1939	frequency	1931:1939	frequency of digalactosylation	1931:1960	The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of β-1,4-galactosyltransferase 1.
35140700	9	87	theme	glycosidases	1325:1336	arg1	expression					1286:1295	the expression	1282:1295	the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines	1282:1388	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	10	88	theme	IgG	1497:1499	arg1	production					1501:1510	IgG production	1497:1510	IgG production	1497:1510	Results We found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns.
35140700	3	89	theme	regulatory	436:445	arg1	mechanisms					447:456	the intracellular regulatory mechanisms	418:456	the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation	418:537	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	9	90	theme	B	1341:1341	arg1	cells					1343:1347	B cells	1341:1347	B cells under stimulation with several cytokines	1341:1388	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	0	91	theme	Immune	17:22	arg1	Microenvironment					24:39	the Immune Microenvironment	13:39	the Immune Microenvironment	13:39	Cytokines in the Immune Microenvironment Change the Glycosylation of IgG by Regulating Intracellular Glycosyltransferases.
35140700	2	92	dep	function	333:340	arg1	the					318:320	the	318:320	the	318:320	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	14	93	theme	IgG	2339:2341	arg1	patterns					2350:2357	IgG glycan patterns	2339:2357	IgG glycan patterns	2339:2357	Conclusion Abnormally elevated cytokines in the microenvironment regulates IgG glycan patterns by regulating intracellular glycosyltransferases in human B cells.
35140700	5	94	theme	B	792:792	arg1	cells					794:798	human CD19+ B cells	780:798	human CD19+ B cells	780:798	Methods First, we established a controlled primary culture system in vitro to differentiate human CD19+ B cells into antibody-secreting cells (ASCs).
35140700	12	95	theme	increased	1873:1881	arg1	frequency					1883:1891	the increased frequency	1869:1891	the increased frequency of mono-galactosylation	1869:1915	The MALDI-TOF-MS data showed that the frequency of agalactosylation was decreased by IFN-γ with the increased frequency of mono-galactosylation and decreased frequency of digalactosylation, accompanied by upregulation of β-1,4-galactosyltransferase 1.
35140700	2	96	theme	many	398:401	arg1	AIDs					403:406	many AIDs	398:406	many AIDs	398:406	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	6	97	theme	IgG	848:850	arg1	concentrations					852:865	the IgG concentrations	844:865	the IgG concentrations in the supernatants	844:885	Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation.
35140700	10	98	theme	different	1545:1553	arg1	patterns					1566:1573	considerably different IgG glycan patterns	1532:1573	considerably different IgG glycan patterns	1532:1573	Results We found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns.
35140700	11	99	theme	lectin	1605:1610	arg1	microarray					1612:1621	lectin microarray	1605:1621	lectin microarray	1605:1621	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	3	100	theme	various	500:506	arg1	cytokines					508:516	various cytokines	500:516	various cytokines	500:516	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	4	101	theme	cytokines	619:627	arg1	effects					599:605	the regulatory effects	584:605	the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells	584:685	Thus, we investigated the regulatory effects of elevated cytokines in AIDs on intracellular IgG glycosylation within B cells.
35140700	3	102	theme	disturbances	484:495	arg1	effects					473:479	the effects	469:479	the effects of disturbances in various cytokines on IgG glycosylation	469:537	However, the intracellular regulatory mechanisms underlying the effects of disturbances in various cytokines on IgG glycosylation are poorly understood.
35140700	10	103	dep	Results	1442:1448	arg1	found					1453:1457	found	1453:1457	found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns	1453:1573	Results We found that cytokines significantly promoted IgG production in vitro and led to considerably different IgG glycan patterns.
35140700	9	104	theme	real-time	1406:1414	arg1	PCR					1416:1418	real-time PCR	1406:1418	real-time PCR	1406:1418	Finally, the expression of glycosyltransferases and glycosidases in B cells under stimulation with several cytokines was detected by real-time PCR and western blotting.
35140700	13	105	gly	disialylated	2065:2076	arg1	N-glycans					2078:2086	mono-sialylated and disialylated N-glycans	2045:2086	mono-sialylated and disialylated N-glycans	2045:2086	Both frequencies of mono-sialylated and disialylated N-glycans were increased by IL-21 and IL-17A with decreased frequency of asialylation, and the expression of β-galactoside α-2,6-sialyltransferase 1 was upregulated by IL-21 and IL-17A.
35140700	6	106	link	enzyme-linked	904:916	arg1	immunoassay					918:928	enzyme-linked immunoassay	904:928	enzyme-linked immunoassay (ELISA)	904:936	Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation.
35140700	6	106	link	enzyme-linked	904:916	arg1	ELISA					931:935	ELISA	931:935	ELISA	931:935	Then, the IgG concentrations in the supernatants were measured by enzyme-linked immunoassay (ELISA) under IFN-γ, TNF-α, IL-21, IL-17A, BAFF, or APRIL stimulation.
35140700	11	107	theme	galactose	1634:1642	arg1	level					1644:1648	the galactose level	1630:1648	the galactose level of IgG	1630:1655	Specifically, the results of lectin microarray showed the galactose level of IgG was increased by IFN-γ stimulation (p<0.05), and the sialylation of IgG was increased by IL-21 and IL-17A (p<0.05).
35140700	2	108	theme	IgG	359:361	arg1	function					333:340	biological function	322:340	biological function	322:340	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
35140700	2	108	theme	IgG	359:361	arg1	stability					346:354	stability	346:354	stability	346:354	The glycosylation patterns of IgG play a critical role in regulating the biological function and stability of IgG involved in the pathophysiology of many AIDs.
33116178	4	0	theme	genome	595:600	arg1	databases					602:610	genome databases	595:610	genome databases	595:610	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	4	1	theme	mansoni	537:543	arg1	SmFucT					565:570	SmFucT	565:570	SmFucT	565:570	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	4	1	theme	mansoni	537:543	arg1	fucosyltransferase					545:562	S. mansoni fucosyltransferase	534:562	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	9	2	theme	glycoproteins	1473:1485	arg1	development					1449:1459	the development	1445:1459	the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines	1445:1549	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
33116178	4	3	theme	S.	534:535	arg1	SmFucT					565:570	SmFucT	565:570	SmFucT	565:570	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	4	3	theme	S.	534:535	arg1	fucosyltransferase					545:562	S. mansoni fucosyltransferase	534:562	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	3	4	theme	human	397:401	arg1	fluke					409:413	the human blood fluke	393:413	the human blood fluke Schistosoma mansoni	393:433	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	6	5	theme	glycan	1045:1050	arg1	motifs					1052:1057	complex antennary glycan motifs	1027:1057	complex antennary glycan motifs	1027:1057	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	3	6	theme	blood	403:407	arg1	fluke					409:413	the human blood fluke	393:413	the human blood fluke Schistosoma mansoni	393:433	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	7	7	theme	glycan	1158:1163	arg1	motifs					1165:1170	specific fucosylated glycan motifs	1137:1170	specific fucosylated glycan motifs of schistosomes	1137:1186	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	9	8	theme	pharmaceutical	1491:1504	arg1	applications					1506:1517	pharmaceutical applications	1491:1517	pharmaceutical applications	1491:1517	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
33116178	5	9	gly	fucosylated	714:724	arg1	N-glycans					726:734	highly fucosylated N-glycans	707:734	highly fucosylated N-glycans	707:734	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	7	10	theme	schistosomes	1175:1186	arg1	motifs					1165:1170	specific fucosylated glycan motifs	1137:1170	specific fucosylated glycan motifs of schistosomes	1137:1186	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	8	11	theme	complex	1292:1298	arg1	structures					1309:1318	complex N-glycan structures	1292:1318	complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation	1292:1390	The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation.
33116178	6	12	theme	complex	1027:1033	arg1	motifs					1052:1057	complex antennary glycan motifs	1027:1057	complex antennary glycan motifs	1027:1057	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	1	13	theme	host	196:199	arg1	responses					208:216	host immune responses	196:216	host immune responses	196:216	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	7	14	theme	specific	1137:1144	arg1	motifs					1165:1170	specific fucosylated glycan motifs	1137:1170	specific fucosylated glycan motifs of schistosomes	1137:1186	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	3	15	dep	fluke	409:413	arg1	mansoni					427:433	Schistosoma mansoni	415:433	the human blood fluke Schistosoma mansoni	393:433	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	9	16	theme	helminth	1464:1471	arg1	glycoproteins					1473:1485	helminth glycoproteins	1464:1485	helminth glycoproteins	1464:1485	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
33116178	1	17	theme	Helminth	104:111	arg1	parasites					113:121	Helminth parasites	104:121	Helminth parasites	104:121	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	1	18	theme	immune	201:206	arg1	responses					208:216	host immune responses	196:216	host immune responses	196:216	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	7	19	theme	starting	1086:1093	arg1	point					1095:1099	a starting point	1084:1099	a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions	1084:1216	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	2	20	theme	important	331:339	arg1	role					341:344	an important role	328:344	an important role	328:344	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	9	21	theme	novel	1522:1526	arg1	vaccines					1542:1549	novel anti-helminth vaccines	1522:1549	novel anti-helminth vaccines	1522:1549	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
33116178	0	22	theme	Functional	0:9	arg1	characterization					11:26	Functional characterization	0:26	Functional characterization of Schistosoma mansoni	0:49	Functional characterization of Schistosoma mansoni fucosyltransferases in Nicotiana benthamiana plants.
33116178	7	23	theme	motifs	1165:1170	arg1	role					1129:1132	the role	1125:1132	the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions	1125:1216	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	6	24	theme	Golgi	918:922	arg1	apparatus					924:932	the plant Golgi apparatus	908:932	the plant Golgi apparatus	908:932	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	6	25	located	localized	895:903	arg2	enzymes					882:888	All enzymes	878:888	All enzymes	878:888	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	6	25	located	localized	895:903	arg1	apparatus					924:932	the plant Golgi apparatus	908:932	the plant Golgi apparatus	908:932	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	0	26	theme	Schistosoma	31:41	arg1	mansoni					43:49	Schistosoma mansoni	31:49	Schistosoma mansoni	31:49	Functional characterization of Schistosoma mansoni fucosyltransferases in Nicotiana benthamiana plants.
33116178	5	27	theme	SmFucTs	791:797	arg1	ability					767:773	the ability	763:773	the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants	763:875	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	8	28	theme	N-glycan	1300:1307	arg1	structures					1309:1318	complex N-glycan structures	1292:1318	complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation	1292:1390	The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation.
33116178	5	29	theme	transient	824:832	arg1	expression					834:843	transient expression	824:843	transient expression in Nicotiana benthamiana plants	824:875	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	5	30	theme	fucosylated	714:724	arg1	N-glycans					726:734	highly fucosylated N-glycans	707:734	highly fucosylated N-glycans	707:734	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	1	31	theme	wide	133:136	arg1	lipids					179:184	lipids	179:184	lipids	179:184	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	1	31	theme	wide	133:136	arg1	variety					138:144	a wide variety	131:144	a wide variety of immunomodulatory proteins and lipids to dampen host immune responses	131:216	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	1	31	theme	wide	133:136	arg1	proteins					166:173	immunomodulatory proteins	149:173	immunomodulatory proteins	149:173	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	6	32	theme	motifs	1052:1057	arg1	fucosylation					993:1004	core fucosylation	988:1004	core fucosylation	988:1004	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	6	32	theme	motifs	1052:1057	arg1	synthesis					1014:1022	the synthesis	1010:1022	the synthesis of complex antennary glycan motifs	1010:1057	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	3	33	theme	Schistosoma	415:425	arg1	mansoni					427:433	Schistosoma mansoni	415:433	the human blood fluke Schistosoma mansoni	393:433	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	5	34	theme	N-glycans	726:734	arg1	synthesis					694:702	the synthesis	690:702	the synthesis of highly fucosylated N-glycans by S. mansoni	690:748	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	6	35	gly	fucosylation	993:1004	arg1	motifs					1052:1057	complex antennary glycan motifs	1027:1057	complex antennary glycan motifs	1027:1057	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	9	36	theme	anti-helminth	1528:1540	arg1	vaccines					1542:1549	novel anti-helminth vaccines	1522:1549	novel anti-helminth vaccines	1522:1549	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
33116178	5	37	theme	Nicotiana	848:856	arg1	plants					870:875	Nicotiana benthamiana plants	848:875	Nicotiana benthamiana plants	848:875	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	0	38	theme	mansoni	43:49	arg1	characterization					11:26	Functional characterization	0:26	Functional characterization of Schistosoma mansoni	0:49	Functional characterization of Schistosoma mansoni fucosyltransferases in Nicotiana benthamiana plants.
33116178	9	39	theme	plant	1411:1415	arg1	system					1428:1433	this plant expression system	1406:1433	this plant expression system	1406:1433	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
33116178	5	40	theme	selected	782:789	arg1	SmFucTs					791:797	ten selected SmFucTs	778:797	ten selected SmFucTs	778:797	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	3	41	gly	glycoproteins	484:496	arg1	glycoproteins					484:496	glycoproteins	484:496	glycoproteins	484:496	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	3	42	from	structures	470:479	arg1	glycolipids					502:512	glycolipids	502:512	glycolipids	502:512	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	3	42	from	structures	470:479	arg1	glycoproteins					484:496	glycoproteins	484:496	glycoproteins	484:496	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	5	43	theme	benthamiana	858:868	arg1	plants					870:875	Nicotiana benthamiana plants	848:875	Nicotiana benthamiana plants	848:875	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	0	44	theme	Nicotiana	74:82	arg1	plants					96:101	Nicotiana benthamiana plants	74:101	Nicotiana benthamiana plants	74:101	Functional characterization of Schistosoma mansoni fucosyltransferases in Nicotiana benthamiana plants.
33116178	4	45	theme	fucosyltransferase	545:562	arg1	genes					573:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	8	46	theme	characterized	1236:1248	arg1	SmFucTs					1250:1256	The functionally characterized SmFucTs	1219:1256	The functionally characterized SmFucTs	1219:1256	The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation.
33116178	3	47	theme	fucosylated	451:461	arg1	example					384:390	an example	381:390	an example	381:390	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	3	47	theme	fucosylated	451:461	arg1	structures					470:479	highly fucosylated glycan structures	444:479	highly fucosylated glycan structures on glycoproteins and glycolipids	444:512	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	7	48	gly	fucosylated	1146:1156	arg1	motifs					1165:1170	specific fucosylated glycan motifs	1137:1170	specific fucosylated glycan motifs of schistosomes	1137:1186	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	2	49	theme	host-parasite	353:365	arg1	interface					367:375	the host-parasite interface	349:375	the host-parasite interface	349:375	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	6	50	theme	plant	912:916	arg1	apparatus					924:932	the plant Golgi apparatus	908:932	the plant Golgi apparatus	908:932	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	7	51	from	role	1129:1132	arg1	interactions					1205:1216	parasite-host interactions	1191:1216	parasite-host interactions	1191:1216	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	2	52	theme	immunomodulatory	233:248	arg1	compounds					250:258	these immunomodulatory compounds	227:258	these immunomodulatory compounds	227:258	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	53	theme	compounds	250:258	arg1	compounds					250:258	these immunomodulatory compounds	227:258	these immunomodulatory compounds	227:258	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	53	theme	compounds	250:258	arg1	Many					219:222	Many	219:222	Many	219:222	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	54	mod	modified	264:271	arg1	compounds					250:258	these immunomodulatory compounds	227:258	these immunomodulatory compounds	227:258	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	54	mod	modified	264:271	arg3	glycans					307:313	glycans	307:313	glycans	307:313	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	54	mod	modified	264:271	arg3	structures					292:301	complex sugar structures	278:301	complex sugar structures (or glycans)	278:314	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	54	mod	modified	264:271	arg1	Many					219:222	Many	219:222	Many	219:222	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	8	55	theme	recombinant	1323:1333	arg1	proteins					1335:1342	recombinant proteins	1323:1342	recombinant proteins	1323:1342	The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation.
33116178	4	56	dep	20	521:522	arg1	to					518:519	to	518:519	to	518:519	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	9	57	gly	glycoproteins	1473:1485	arg1	glycoproteins					1473:1485	helminth glycoproteins	1464:1485	helminth glycoproteins	1464:1485	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
33116178	7	58	theme	fucosylated	1146:1156	arg1	motifs					1165:1170	specific fucosylated glycan motifs	1137:1170	specific fucosylated glycan motifs of schistosomes	1137:1186	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	1	59	theme	immunomodulatory	149:164	arg1	proteins					166:173	immunomodulatory proteins	149:173	immunomodulatory proteins	149:173	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	5	60	from	expression	834:843	arg1	plants					870:875	Nicotiana benthamiana plants	848:875	Nicotiana benthamiana plants	848:875	To unravel the synthesis of highly fucosylated N-glycans by S. mansoni, we examined the ability of ten selected SmFucTs to modify N-glycans upon transient expression in Nicotiana benthamiana plants.
33116178	6	61	theme	core	988:991	arg1	fucosylation					993:1004	core fucosylation	988:1004	core fucosylation	988:1004	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	4	62	located	found	586:590	arg1	databases					602:610	genome databases	595:610	genome databases	595:610	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	4	62	located	found	586:590	arg2	genes					573:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	3	63	gly	fucosylated	451:461	arg1	example					384:390	an example	381:390	an example	381:390	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	3	63	gly	fucosylated	451:461	arg1	structures					470:479	highly fucosylated glycan structures	444:479	highly fucosylated glycan structures on glycoproteins and glycolipids	444:512	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	1	64	theme	proteins	166:173	arg1	lipids					179:184	lipids	179:184	lipids	179:184	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	1	64	theme	proteins	166:173	arg1	variety					138:144	a wide variety	131:144	a wide variety of immunomodulatory proteins and lipids to dampen host immune responses	131:216	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	1	64	theme	proteins	166:173	arg1	proteins					166:173	immunomodulatory proteins	149:173	immunomodulatory proteins	149:173	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	6	65	theme	antennary	1035:1043	arg1	motifs					1052:1057	complex antennary glycan motifs	1027:1057	complex antennary glycan motifs	1027:1057	All enzymes were localized in the plant Golgi apparatus, which allowed us to identify the SmFucTs involved in core fucosylation and the synthesis of complex antennary glycan motifs.
33116178	2	66	theme	sugar	286:290	arg1	structures					292:301	complex sugar structures	278:301	complex sugar structures (or glycans)	278:314	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	66	theme	sugar	286:290	arg1	glycans					307:313	glycans	307:313	glycans	307:313	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	8	67	from	structures	1309:1318	arg1	proteins					1335:1342	recombinant proteins	1323:1342	recombinant proteins	1323:1342	The functionally characterized SmFucTs can also be applied to synthesize complex N-glycan structures on recombinant proteins to study their contribution to immunomodulation.
33116178	3	68	theme	glycan	463:468	arg1	example					384:390	an example	381:390	an example	381:390	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	3	68	theme	glycan	463:468	arg1	structures					470:479	highly fucosylated glycan structures	444:479	highly fucosylated glycan structures on glycoproteins and glycolipids	444:512	As an example, the human blood fluke Schistosoma mansoni produces highly fucosylated glycan structures on glycoproteins and glycolipids.
33116178	0	69	theme	benthamiana	84:94	arg1	plants					96:101	Nicotiana benthamiana plants	74:101	Nicotiana benthamiana plants	74:101	Functional characterization of Schistosoma mansoni fucosyltransferases in Nicotiana benthamiana plants.
33116178	4	70	theme	different	524:532	arg1	genes					573:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes	515:577	Up to 20 different S. mansoni fucosyltransferase (SmFucT) genes can be found in genome databases, but thus far only one enzyme has been functionally characterized.
33116178	2	71	theme	complex	278:284	arg1	structures					292:301	complex sugar structures	278:301	complex sugar structures (or glycans)	278:314	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	2	71	theme	complex	278:284	arg1	glycans					307:313	glycans	307:313	glycans	307:313	Many of these immunomodulatory compounds are modified with complex sugar structures (or glycans), which play an important role at the host-parasite interface.
33116178	1	72	theme	lipids	179:184	arg1	lipids					179:184	lipids	179:184	lipids	179:184	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	1	72	theme	lipids	179:184	arg1	variety					138:144	a wide variety	131:144	a wide variety of immunomodulatory proteins and lipids to dampen host immune responses	131:216	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	1	72	theme	lipids	179:184	arg1	proteins					166:173	immunomodulatory proteins	149:173	immunomodulatory proteins	149:173	Helminth parasites secrete a wide variety of immunomodulatory proteins and lipids to dampen host immune responses.
33116178	7	73	theme	parasite-host	1191:1203	arg1	interactions					1205:1216	parasite-host interactions	1191:1216	parasite-host interactions	1191:1216	This knowledge provides a starting point for investigations into the role of specific fucosylated glycan motifs of schistosomes in parasite-host interactions.
33116178	9	74	theme	expression	1417:1426	arg1	system					1428:1433	this plant expression system	1406:1433	this plant expression system	1406:1433	Furthermore, this plant expression system will fuel the development of helminth glycoproteins for pharmaceutical applications or novel anti-helminth vaccines.
32946227	5	0	theme	other	910:914	arg1	results					916:922	other results	910:922	other results from spectroscopic, microscopic, and rheological experiments	910:983	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	1	1	theme	self-assembling	197:211	arg1	glycopeptides					213:225	self-assembling glycopeptides	197:225	self-assembling glycopeptides	197:225	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	6	2	theme	mechanistic	1089:1099	arg1	findings					1101:1108	These mechanistic findings	1083:1108	These mechanistic findings	1083:1108	These mechanistic findings, particularly evidence obtained at the angstrom scale, illuminate an unconventional role that carbohydrates can play in building supramolecules.
32946227	6	2	theme	mechanistic	1089:1099	arg1	evidence					1124:1131	evidence	1124:1131	evidence obtained at the angstrom scale	1124:1162	These mechanistic findings, particularly evidence obtained at the angstrom scale, illuminate an unconventional role that carbohydrates can play in building supramolecules.
32946227	7	3	theme	enzyme-resistant	1345:1360	arg1	hydrogel					1362:1369	an enzyme-resistant hydrogel	1342:1369	an enzyme-resistant hydrogel	1342:1369	Potential biomaterials exploiting the CH-π bond-based stabilization, as exemplified by an enzyme-resistant hydrogel, may thus be developed.
32946227	6	4	theme	unconventional	1179:1192	arg1	role					1194:1197	an unconventional role that carbohydrates can play in building supramolecules	1176:1252	an unconventional role that carbohydrates can play in building supramolecules	1176:1252	These mechanistic findings, particularly evidence obtained at the angstrom scale, illuminate an unconventional role that carbohydrates can play in building supramolecules.
32946227	3	5	theme	tyrosine-rich	438:450	arg1	system					465:470	a dimeric tyrosine-rich glycopeptide system	428:470	a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations	428:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	7	6	dep	developed	1384:1392	arg1	exemplified					1327:1337	exemplified	1327:1337	exemplified by an enzyme-resistant hydrogel	1327:1369	Potential biomaterials exploiting the CH-π bond-based stabilization, as exemplified by an enzyme-resistant hydrogel, may thus be developed.
32946227	2	7	theme	self-assembly	364:376	arg1	process					378:384	the self-assembly process	360:384	the self-assembly process	360:384	However, how stereochemistry of carbohydrates impacts the self-assembly process remains unclear.
32946227	3	8	theme	glycopeptide	452:463	arg1	system					465:470	a dimeric tyrosine-rich glycopeptide system	428:470	a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations	428:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	1	9	from	bonds	188:192	arg1	glycopeptides					213:225	self-assembling glycopeptides	197:225	self-assembling glycopeptides	197:225	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	4	10	with	glycopeptides	674:686	arg1	β-anomers					706:714	β-anomers	706:714	β-anomers	706:714	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	4	10	with	glycopeptides	674:686	arg1	α-					700:701	α-	700:701	α-	700:701	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	5	11	theme	gelator	890:896	arg1	structure					850:858	A high-resolution X-ray crystallographic structure	809:858	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator	809:896	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	5	12	from	experiments	973:983	arg1	results					916:922	other results	910:922	other results from spectroscopic, microscopic, and rheological experiments	910:983	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	4	13	theme	hydroxyl	792:799	arg1	groups					801:806	axial hydroxyl groups	786:806	axial hydroxyl groups	786:806	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	5	14	theme	carbohydrate-aromatic	1006:1026	arg1	bonding					1033:1039	an unusual carbohydrate-aromatic CH-π bonding	995:1039	an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly	995:1080	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	3	15	theme	dimeric	430:436	arg1	system					465:470	a dimeric tyrosine-rich glycopeptide system	428:470	a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations	428:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	4	16	theme	glycoforms	606:615	arg1	Comparison					589:598	Comparison	589:598	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4'	589:657	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	2	17	theme	carbohydrates	338:350	arg1	stereochemistry					319:333	stereochemistry	319:333	stereochemistry of carbohydrates	319:350	However, how stereochemistry of carbohydrates impacts the self-assembly process remains unclear.
32946227	3	18	theme	site-	548:552	arg1	glycosylations					573:586	site- and stereospecific glycosylations	548:586	site- and stereospecific glycosylations	548:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	5	19	theme	unusual	998:1004	arg1	bonding					1033:1039	an unusual carbohydrate-aromatic CH-π bonding	995:1039	an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly	995:1080	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	7	20	theme	CH-π	1293:1296	arg1	stabilization					1309:1321	the CH-π bond-based stabilization	1289:1321	the CH-π bond-based stabilization	1289:1321	Potential biomaterials exploiting the CH-π bond-based stabilization, as exemplified by an enzyme-resistant hydrogel, may thus be developed.
32946227	1	21	theme	versatile	238:246	arg1	scaffolds					248:256	versatile scaffolds	238:256	versatile scaffolds	238:256	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	0	22	theme	Glycopeptide	0:11	arg1	Self-Assembly					13:25	Glycopeptide Self-Assembly	0:25	Glycopeptide Self-Assembly	0:25	Glycopeptide Self-Assembly Modulated by Glycan Stereochemistry through Glycan-Aromatic Interactions.
32946227	7	23	theme	bond-based	1298:1307	arg1	stabilization					1309:1321	the CH-π bond-based stabilization	1289:1321	the CH-π bond-based stabilization	1289:1321	Potential biomaterials exploiting the CH-π bond-based stabilization, as exemplified by an enzyme-resistant hydrogel, may thus be developed.
32946227	1	24	from	hydrophilicity	145:158	arg1	glycopeptides					213:225	self-assembling glycopeptides	197:225	self-assembling glycopeptides	197:225	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	4	25	theme	axial	786:790	arg1	groups					801:806	axial hydroxyl groups	786:806	axial hydroxyl groups	786:806	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	5	26	theme	rheological	961:971	arg1	experiments					973:983	spectroscopic, microscopic, and rheological experiments	929:983	spectroscopic, microscopic, and rheological experiments	929:983	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	3	27	gly	glycopeptide	452:463	arg2	glycopeptide					452:463	a dimeric tyrosine-rich glycopeptide system	428:470	a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations	428:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	3	28	theme	glycosylations	573:586	arg1	influence					535:543	the influence	531:543	the influence of site- and stereospecific glycosylations	531:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	6	29	theme	angstrom	1149:1156	arg1	scale					1158:1162	the angstrom scale	1145:1162	the angstrom scale	1145:1162	These mechanistic findings, particularly evidence obtained at the angstrom scale, illuminate an unconventional role that carbohydrates can play in building supramolecules.
32946227	5	30	theme	crystallographic	833:848	arg1	structure					850:858	A high-resolution X-ray crystallographic structure	809:858	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator	809:896	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	5	31	theme	microscopic	944:954	arg1	experiments					973:983	spectroscopic, microscopic, and rheological experiments	929:983	spectroscopic, microscopic, and rheological experiments	929:983	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	1	32	theme	wide	263:266	arg1	applicability					268:280	wide applicability	263:280	wide applicability in biomedical research	263:303	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	7	33	theme	Potential	1255:1263	arg1	biomaterials					1265:1276	Potential biomaterials	1255:1276	Potential biomaterials exploiting the CH-π bond-based stabilization	1255:1321	Potential biomaterials exploiting the CH-π bond-based stabilization, as exemplified by an enzyme-resistant hydrogel, may thus be developed.
32946227	6	34	theme	building	1230:1237	arg1	supramolecules					1239:1252	building supramolecules	1230:1252	building supramolecules	1230:1252	These mechanistic findings, particularly evidence obtained at the angstrom scale, illuminate an unconventional role that carbohydrates can play in building supramolecules.
32946227	4	35	theme	glycan	762:767	arg1	moieties					769:776	the glycan moieties	758:776	the glycan moieties	758:776	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	0	36	theme	Glycan	40:45	arg1	Stereochemistry					47:61	Glycan Stereochemistry	40:61	Glycan Stereochemistry	40:61	Glycopeptide Self-Assembly Modulated by Glycan Stereochemistry through Glycan-Aromatic Interactions.
32946227	5	37	theme	spectroscopic	929:941	arg1	experiments					973:983	spectroscopic, microscopic, and rheological experiments	929:983	spectroscopic, microscopic, and rheological experiments	929:983	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	5	38	theme	β-galactose-containing	867:888	arg1	gelator					890:896	the β-galactose-containing gelator	863:896	the β-galactose-containing gelator	863:896	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	1	39	from	applicability	268:280	arg1	research					296:303	biomedical research	285:303	biomedical research	285:303	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	3	40	theme	stereospecific	558:571	arg1	glycosylations					573:586	site- and stereospecific glycosylations	548:586	site- and stereospecific glycosylations	548:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	3	41	theme	corresponding	488:500	arg1	behavior					516:523	the corresponding hydrogelating behavior	484:523	the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations	484:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	5	42	gly	glycopeptide	1055:1066	arg2	glycopeptide					1055:1066	glycopeptide self-assembly	1055:1080	glycopeptide self-assembly	1055:1080	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	3	43	theme	hydrogelating	502:514	arg1	behavior					516:523	the corresponding hydrogelating behavior	484:523	the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations	484:586	Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations.
32946227	5	44	theme	X-ray	827:831	arg1	structure					850:858	A high-resolution X-ray crystallographic structure	809:858	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator	809:896	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	4	45	gly	glycopeptides	674:686	arg2	glycopeptides					674:686	the glycopeptides	670:686	the glycopeptides with either α- or β-anomers	670:714	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	1	46	gly	glycopeptides	213:225	arg2	glycopeptides					213:225	self-assembling glycopeptides	197:225	self-assembling glycopeptides	197:225	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	1	47	used	utilized	125:132	arg2	Carbohydrates					101:113	Carbohydrates	101:113	Carbohydrates	101:113	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	1	48	theme	biomedical	285:294	arg1	research					296:303	biomedical research	285:303	biomedical research	285:303	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	5	49	theme	high-resolution	811:825	arg1	structure					850:858	A high-resolution X-ray crystallographic structure	809:858	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator	809:896	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	1	50	theme	hydrogen	179:186	arg1	bonds					188:192	hydroxyl-based hydrogen bonds	164:192	hydroxyl-based hydrogen bonds in self-assembling glycopeptides	164:225	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	1	51	theme	hydroxyl-based	164:177	arg1	bonds					188:192	hydroxyl-based hydrogen bonds	164:192	hydroxyl-based hydrogen bonds in self-assembling glycopeptides	164:225	Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research.
32946227	4	52	contain	contain	778:784	arg2	groups					801:806	axial hydroxyl groups	786:806	axial hydroxyl groups	786:806	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	4	52	contain	contain	778:784	arg1	moieties					769:776	the glycan moieties	758:776	the glycan moieties	758:776	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	5	53	theme	glycopeptide	1055:1066	arg1	self-assembly					1068:1080	glycopeptide self-assembly	1055:1080	glycopeptide self-assembly	1055:1080	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	5	54	theme	CH-π	1028:1031	arg1	bonding					1033:1039	an unusual carbohydrate-aromatic CH-π bonding	995:1039	an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly	995:1080	A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly.
32946227	0	55	theme	Glycan-Aromatic	71:85	arg1	Interactions					87:98	Glycan-Aromatic Interactions	71:98	Glycan-Aromatic Interactions	71:98	Glycopeptide Self-Assembly Modulated by Glycan Stereochemistry through Glycan-Aromatic Interactions.
32946227	4	56	theme	contrary	724:731	arg1	abilities					742:750	contrary gelating abilities	724:750	contrary gelating abilities	724:750	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
32946227	4	57	theme	gelating	733:740	arg1	abilities					742:750	contrary gelating abilities	724:750	contrary gelating abilities	724:750	Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups.
34864058	4	0	theme	IL-22	622:626	arg1	signaling					628:636	IL-22 signaling	622:636	IL-22 signaling	622:636	Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice.
34864058	3	1	theme	junction	532:539	arg1	fortification					541:553	tight junction fortification	526:553	tight junction fortification	526:553	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	6	2	theme	IL-22	957:961	arg1	signaling					963:971	IL-22 signaling	957:971	IL-22 signaling	957:971	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	2	3	theme	IL-22	295:299	arg1	receptor					301:308	the heterodimeric IL-22 receptor	277:308	the heterodimeric IL-22 receptor	277:308	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	9	4	from	intermediary	1645:1656	arg1	induction					1677:1685	IL-22-dependent induction	1661:1685	IL-22-dependent induction of fucosylation of glycoproteins	1661:1718	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	7	5	theme	IL-22	1187:1191	arg1	signaling					1193:1201	IL-22 signaling	1187:1201	IL-22 signaling	1187:1201	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	3	6	theme	antimicrobial	560:572	arg1	production					574:583	antimicrobial production	560:583	antimicrobial production	560:583	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	1	7	theme	critical	162:169	arg1	role					171:174	a critical role	160:174	a critical role	160:174	Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis.
34864058	8	8	gly	glycoproteins	1587:1599	arg1	glycoproteins					1587:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	4	9	theme	fucosylation	681:692	arg1	regulation					645:654	the regulation	641:654	the regulation of intestinal epithelial fucosylation in mice	641:700	Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice.
34864058	5	10	theme	human	763:767	arg1	cells					791:795	human intestinal epithelial cells	763:795	human intestinal epithelial cells	763:795	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	1	11	theme	epithelial	190:199	arg1	homeostasis					201:211	intestinal epithelial homeostasis	179:211	intestinal epithelial homeostasis	179:211	Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis.
34864058	8	12	theme	O-glycosylated	1550:1563	arg1	glycoproteins					1587:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	5	13	theme	epithelial	780:789	arg1	cells					791:795	human intestinal epithelial cells	763:795	human intestinal epithelial cells	763:795	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	6	14	theme	B3GNT7	1001:1006	arg1	transcript					1008:1017	the B3GNT7 transcript	997:1017	the B3GNT7 transcript	997:1017	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	8	15	theme	epithelial	1576:1585	arg1	glycoproteins					1587:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	2	16	with	interaction	260:270	arg1	receptor					301:308	the heterodimeric IL-22 receptor	277:308	the heterodimeric IL-22 receptor	277:308	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	0	17	theme	glycoproteins	69:81	arg1	fucosylation					53:64	fucosylation	53:64	fucosylation of glycoproteins	53:81	Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells.
34864058	7	18	theme	Lex	1253:1255	arg1	antigen					1270:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	5	19	gly	fucosylation	747:758	arg1	cells					791:795	human intestinal epithelial cells	763:795	human intestinal epithelial cells	763:795	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	0	20	theme	intestinal	86:95	arg1	cells					108:112	intestinal epithelial cells	86:112	intestinal epithelial cells	86:112	Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells.
34864058	9	21	theme	IL-22-dependent	1661:1675	arg1	induction					1677:1685	IL-22-dependent induction	1661:1685	IL-22-dependent induction of fucosylation of glycoproteins	1661:1718	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	9	22	from	induction	1677:1685	arg1	B3GNT7					1632:1637	B3GNT7	1632:1637	B3GNT7	1632:1637	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	9	22	from	induction	1677:1685	arg1	intermediary					1645:1656	intermediary	1645:1656	intermediary	1645:1656	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	8	23	theme	B3GNT7	1433:1438	arg1	expression					1419:1428	increased expression	1409:1428	increased expression of B3GNT7	1409:1438	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	2	24	with	activation	325:334	arg1	receptor					301:308	the heterodimeric IL-22 receptor	277:308	the heterodimeric IL-22 receptor	277:308	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	3	25	theme	necessary	449:457	arg1	genes					443:447	genes	443:447	genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production	443:583	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	7	26	theme	antigen	1270:1276	arg1	levels					1213:1218	levels	1213:1218	levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen	1213:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	7	27	theme	blood	1258:1262	arg1	antigen					1270:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	6	28	theme	chains	1152:1157	arg1	synthesis					1101:1109	the synthesis	1097:1109	the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains	1097:1157	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	4	29	theme	Recent	586:591	arg1	studies					593:599	Recent studies	586:599	Recent studies	586:599	Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice.
34864058	8	30	theme	increased	1471:1479	arg1	display					1481:1487	increased display	1471:1487	increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins	1471:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	3	31	theme	cell	485:488	arg1	proliferation					490:502	intestinal epithelial cell proliferation	463:502	intestinal epithelial cell proliferation	463:502	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	0	32	theme	B3GNT7	25:30	arg1	expression					32:41	B3GNT7 expression	25:41	B3GNT7 expression	25:41	Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells.
34864058	6	33	theme	polyLacNAc	1140:1149	arg1	chains					1152:1157	poly-N-acetyllactosamine (polyLacNAc) chains	1114:1157	poly-N-acetyllactosamine (polyLacNAc) chains	1114:1157	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	9	34	gly	fucosylation	1690:1701	arg1	glycoproteins					1706:1718	glycoproteins	1706:1718	glycoproteins	1706:1718	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	3	35	theme	intestinal	463:472	arg1	proliferation					490:502	intestinal epithelial cell proliferation	463:502	intestinal epithelial cell proliferation	463:502	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	7	36	theme	X	1250:1250	arg1	antigen					1270:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	6	37	theme	poly-N-acetyllactosamine	1114:1137	arg1	chains					1152:1157	poly-N-acetyllactosamine (polyLacNAc) chains	1114:1157	poly-N-acetyllactosamine (polyLacNAc) chains	1114:1157	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	9	38	gly	glycoproteins	1706:1718	arg1	glycoproteins					1706:1718	glycoproteins	1706:1718	glycoproteins	1706:1718	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	7	39	gly	α1-3-fucosylated	1227:1242	arg1	antigen					1270:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	2	40	theme	activator	361:369	arg1	activation					325:334	subsequent activation	314:334	subsequent activation of signal transducer and activator of transcription 3 (STAT3)	314:396	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	2	40	theme	activator	361:369	arg1	interaction					260:270	interaction	260:270	interaction with the heterodimeric IL-22 receptor	260:308	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	7	41	theme	α1-3-fucosylated	1227:1242	arg1	antigen					1270:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	6	42	theme	cell	904:907	arg1	lines					909:913	human cell lines	898:913	human cell lines	898:913	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	8	43	theme	structures	1526:1535	arg1	display					1481:1487	increased display	1471:1487	increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins	1471:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	2	44	theme	transducer	346:355	arg1	activation					325:334	subsequent activation	314:334	subsequent activation of signal transducer and activator of transcription 3 (STAT3)	314:396	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	2	44	theme	transducer	346:355	arg1	interaction					260:270	interaction	260:270	interaction with the heterodimeric IL-22 receptor	260:308	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	7	45	gly	O-glycosylated	1334:1347	arg1	glycoproteins					1371:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	0	46	gly	induce	46:51	arg1	cells					108:112	intestinal epithelial cells	86:112	intestinal epithelial cells	86:112	Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells.
34864058	7	47	theme	intestinal	1349:1358	arg1	glycoproteins					1371:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	3	48	theme	epithelial	474:483	arg1	proliferation					490:502	intestinal epithelial cell proliferation	463:502	intestinal epithelial cell proliferation	463:502	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	4	49	from	regulation	645:654	arg1	mice					697:700	mice	697:700	mice	697:700	Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice.
34864058	2	50	theme	transcription	374:386	arg1	STAT3					391:395	STAT3	391:395	STAT3	391:395	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	2	50	theme	transcription	374:386	arg1	activator					361:369	activator	361:369	activator of transcription 3	361:388	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	2	50	theme	transcription	374:386	arg1	transducer					346:355	signal transducer	339:355	signal transducer	339:355	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	8	51	theme	carbohydrate	1506:1517	arg1	structures					1526:1535	Lex-decorated carbohydrate glycan structures	1492:1535	Lex-decorated carbohydrate glycan structures	1492:1535	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	2	52	theme	heterodimeric	281:293	arg1	receptor					301:308	the heterodimeric IL-22 receptor	277:308	the heterodimeric IL-22 receptor	277:308	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	8	53	gly	O-glycosylated	1550:1563	arg1	glycoproteins					1587:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	8	54	from	display	1481:1487	arg1	glycoproteins					1587:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	2	55	theme	subsequent	314:323	arg1	activation					325:334	subsequent activation	314:334	subsequent activation of signal transducer and activator of transcription 3 (STAT3)	314:396	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	1	56	theme	intestinal	179:188	arg1	homeostasis					201:211	intestinal epithelial homeostasis	179:211	intestinal epithelial homeostasis	179:211	Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis.
34864058	8	57	theme	intestinal	1565:1574	arg1	glycoproteins					1587:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	O-glycosylated intestinal epithelial glycoproteins	1550:1599	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	4	58	theme	epithelial	670:679	arg1	fucosylation					681:692	intestinal epithelial fucosylation	659:692	intestinal epithelial fucosylation	659:692	Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice.
34864058	3	59	theme	tight	526:530	arg1	fortification					541:553	tight junction fortification	526:553	tight junction fortification	526:553	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	5	60	theme	intestinal	769:778	arg1	cells					791:795	human intestinal epithelial cells	763:795	human intestinal epithelial cells	763:795	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	6	61	theme	transcript	1008:1017	arg1	β1-3-N-acetylglucosaminyltransferase					1036:1071	a β1-3-N-acetylglucosaminyltransferase	1034:1071	a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains	1034:1157	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	6	61	theme	transcript	1008:1017	arg1	expression					983:992	expression	983:992	expression	983:992	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	2	62	theme	downstream	218:227	arg1	functions					229:237	Its downstream functions	214:237	Its downstream functions	214:237	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	5	63	theme	intestinal	736:745	arg1	fucosylation					747:758	intestinal fucosylation	736:758	intestinal fucosylation in human intestinal epithelial cells	736:795	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	7	64	theme	glycan	1293:1298	arg1	epitope					1300:1306	this glycan epitope	1288:1306	this glycan epitope	1288:1306	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	3	65	theme	tissue	505:510	arg1	regeneration					512:523	tissue regeneration	505:523	tissue regeneration	505:523	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	0	66	theme	epithelial	97:106	arg1	cells					108:112	intestinal epithelial cells	86:112	intestinal epithelial cells	86:112	Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells.
34864058	8	67	theme	increased	1409:1417	arg1	expression					1419:1428	increased expression	1409:1428	increased expression of B3GNT7	1409:1438	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	9	68	theme	intestinal	1759:1768	arg1	glycosylation					1770:1782	intestinal glycosylation	1759:1782	intestinal glycosylation	1759:1782	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	0	69	gly	glycoproteins	69:81	arg1	glycoproteins					69:81	glycoproteins	69:81	glycoproteins	69:81	Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells.
34864058	2	70	theme	signal	339:344	arg1	STAT3					391:395	STAT3	391:395	STAT3	391:395	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	2	70	theme	signal	339:344	arg1	transducer					346:355	signal transducer	339:355	signal transducer	339:355	Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3).
34864058	7	71	theme	group	1264:1268	arg1	antigen					1270:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	9	72	theme	fucosylation	1690:1701	arg1	induction					1677:1685	IL-22-dependent induction	1661:1685	IL-22-dependent induction of fucosylation of glycoproteins	1661:1718	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	9	73	theme	glycoproteins	1706:1718	arg1	fucosylation					1690:1701	fucosylation	1690:1701	fucosylation of glycoproteins	1690:1718	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	3	74	theme	IL-22	399:403	arg1	signaling					405:413	IL-22 signaling	399:413	IL-22 signaling	399:413	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	3	75	theme	genes	443:447	arg1	transcription					426:438	transcription	426:438	transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production	426:583	IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production.
34864058	1	76	theme	Interleukin	115:125	arg1	cytokine					140:147	a cytokine	138:147	a cytokine that plays a critical role in intestinal epithelial homeostasis	138:211	Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis.
34864058	1	76	theme	Interleukin	115:125	arg1	IL					128:129	Interleukin (IL)-22	115:133	Interleukin (IL)-22	115:133	Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis.
34864058	7	77	theme	Lewis	1244:1248	arg1	antigen					1270:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	the α1-3-fucosylated Lewis X (Lex) blood group antigen	1223:1276	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	6	78	theme	human-derived	919:931	arg1	enteroids					933:941	human-derived enteroids	919:941	human-derived enteroids	919:941	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	9	79	theme	novel	1734:1738	arg1	role					1740:1743	a novel role	1732:1743	a novel role for B3GNT7 in intestinal glycosylation	1732:1782	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	9	80	from	role	1740:1743	arg1	glycosylation					1770:1782	intestinal glycosylation	1759:1782	intestinal glycosylation	1759:1782	Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
34864058	5	81	theme	molecular	805:813	arg1	unknown					855:861	unknown	855:861	unknown	855:861	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	5	81	theme	molecular	805:813	arg1	mechanisms					815:824	the molecular mechanisms	801:824	the molecular mechanisms that govern this process	801:849	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	7	82	gly	glycoproteins	1371:1383	arg1	glycoproteins					1371:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	7	83	theme	epithelial	1360:1369	arg1	glycoproteins					1371:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	8	84	theme	Lex-decorated	1492:1504	arg1	structures					1526:1535	Lex-decorated carbohydrate glycan structures	1492:1535	Lex-decorated carbohydrate glycan structures	1492:1535	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	6	85	theme	human	898:902	arg1	lines					909:913	human cell lines	898:913	human cell lines	898:913	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	7	86	theme	O-glycosylated	1334:1347	arg1	glycoproteins					1371:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	O-glycosylated intestinal epithelial glycoproteins	1334:1383	Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins.
34864058	8	87	theme	glycan	1519:1524	arg1	structures					1526:1535	Lex-decorated carbohydrate glycan structures	1492:1535	Lex-decorated carbohydrate glycan structures	1492:1535	Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins.
34864058	6	88	link	human-derived	919:931	arg1	enteroids					933:941	human-derived enteroids	919:941	human-derived enteroids	919:941	Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains.
34864058	5	89	from	fucosylation	747:758	arg1	cells					791:795	human intestinal epithelial cells	763:795	human intestinal epithelial cells	763:795	However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown.
34864058	0	90	gly	fucosylation	53:64	arg1	glycoproteins					69:81	glycoproteins	69:81	glycoproteins	69:81	Interleukin-22 regulates B3GNT7 expression to induce fucosylation of glycoproteins in intestinal epithelial cells.
34864058	4	91	theme	intestinal	659:668	arg1	fucosylation					681:692	intestinal epithelial fucosylation	659:692	intestinal epithelial fucosylation	659:692	Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice.
33947960	4	0	theme	α2,6-	881:885	arg1	structures					914:923	both α2,6- and α2,3-sialylated glycan structures	876:923	both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens	876:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	6	1	theme	ErbB2	1375:1379	arg1	receptor					1381:1388	the ErbB2 receptor	1371:1388	the ErbB2 receptor	1371:1388	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	4	2	theme	α2,3-sialylated	891:905	arg1	structures					914:923	both α2,6- and α2,3-sialylated glycan structures	876:923	both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens	876:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	6	3	theme	ST6Gal1	1266:1272	arg1	expression					1274:1283	ST6Gal1 expression	1266:1283	ST6Gal1 expression	1266:1283	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	3	4	theme	GC	748:749	arg1	cells					751:755	ErbB2-addicted GC cells	733:755	ErbB2-addicted GC cells	733:755	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	6	5	theme	cellular	1349:1356	arg1	half-life					1358:1366	the cellular half-life	1345:1366	the cellular half-life of the ErbB2 receptor	1345:1388	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	1	6	theme	monoclonal	172:181	arg1	trastuzumab					192:202	the therapeutic monoclonal antibody trastuzumab	156:202	the therapeutic monoclonal antibody trastuzumab	156:202	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	1	7	theme	trastuzumab	192:202	arg1	performance					141:151	The clinical performance	128:151	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC)	128:270	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	3	8	theme	glycan	564:569	arg1	ErbB2					585:589	ErbB2	585:589	ErbB2	585:589	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	8	theme	glycan	564:569	arg1	repertoire					571:580	the site-specific glycan repertoire	546:580	the site-specific glycan repertoire of ErbB2	546:589	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	9	theme	resistance	799:808	arg1	acquisition					772:782	the acquisition	768:782	the acquisition of trastuzumab resistance	768:808	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	6	10	theme	GC	1422:1423	arg1	cells					1425:1429	ErbB2-dependent GC cells	1406:1429	ErbB2-dependent GC cells	1406:1429	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	5	11	theme	ST6Gal1	1117:1123	arg1	sialyltransferase					1125:1141	the ST6Gal1 sialyltransferase	1113:1141	the ST6Gal1 sialyltransferase	1113:1141	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	6	12	theme	ErbB2-specific	1311:1324	arg1	glycomes					1326:1333	the cellular and ErbB2-specific glycomes	1294:1333	the cellular and ErbB2-specific glycomes	1294:1333	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	5	13	theme	GC	1094:1095	arg1	cells					1097:1101	GC cells	1094:1101	GC cells	1094:1101	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	4	14	theme	GC	928:929	arg1	specimens					940:948	GC clinical specimens	928:948	GC clinical specimens	928:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	6	15	theme	cellular	1298:1305	arg1	glycomes					1326:1333	the cellular and ErbB2-specific glycomes	1294:1333	the cellular and ErbB2-specific glycomes	1294:1333	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	4	16	from	structures	914:923	arg1	specimens					940:948	GC clinical specimens	928:948	GC clinical specimens	928:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	3	17	theme	molecular	616:624	arg1	mechanisms					626:635	the detailed molecular mechanisms	603:635	the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance	603:808	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	5	18	theme	In-depth	951:958	arg1	analysis					1012:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis	951:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain	951:1041	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	7	19	theme	cells	1716:1720	arg1	resistance					1686:1695	the resistance	1682:1695	the resistance of ErbB2-driven GC cells to trastuzumab	1682:1735	Overall, our data demonstrates that ST6Gal1-mediated aberrant α2,6-sialylation actively tunes the resistance of ErbB2-driven GC cells to trastuzumab.
33947960	6	20	theme	dimers	1501:1506	arg1	stabilization					1479:1491	the stabilization	1475:1491	the stabilization of ErbB dimers at the cell membrane	1475:1527	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	6	20	theme	dimers	1501:1506	arg1	activation					1548:1557	the decreased activation	1534:1557	the decreased activation of both ErbB2 and EGFR RTKs	1534:1585	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	4	21	mod	modified	862:869	arg1	ErbB2					853:857	ErbB2	853:857	ErbB2	853:857	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	4	21	mod	modified	862:869	arg3	structures					914:923	both α2,6- and α2,3-sialylated glycan structures	876:923	both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens	876:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	7	22	theme	ErbB2-driven	1700:1711	arg1	cells					1716:1720	ErbB2-driven GC cells	1700:1720	ErbB2-driven GC cells	1700:1720	Overall, our data demonstrates that ST6Gal1-mediated aberrant α2,6-sialylation actively tunes the resistance of ErbB2-driven GC cells to trastuzumab.
33947960	2	23	link	N-linked	513:520	arg1	glycosylation					522:534	extensive N-linked glycosylation	503:534	extensive N-linked glycosylation	503:534	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	0	24	theme	gastric	80:86	arg1	sensitivity					100:110	gastric cancer cell sensitivity	80:110	gastric cancer cell sensitivity	80:110	ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab.
33947960	2	25	gly	glycosylation	522:534	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	2	26	theme	extensive	503:511	arg1	glycosylation					522:534	extensive N-linked glycosylation	503:534	extensive N-linked glycosylation	503:534	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	0	27	theme	cell	95:98	arg1	sensitivity					100:110	gastric cancer cell sensitivity	80:110	gastric cancer cell sensitivity	80:110	ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab.
33947960	5	28	theme	ErbB2	1164:1168	arg1	sites					1186:1190	ErbB2 N-glycosylation sites	1164:1190	ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain	1164:1249	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	2	29	theme	extracellular	388:400	arg1	domain					402:407	the extracellular domain	384:407	the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation	384:534	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	2	29	theme	extracellular	388:400	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	6	30	theme	decreased	1538:1546	arg1	activation					1548:1557	the decreased activation	1534:1557	the decreased activation of both ErbB2 and EGFR RTKs	1534:1585	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	5	31	theme	spectrometry-based	965:982	arg1	analysis					1012:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis	951:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain	951:1041	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	2	32	theme	tyrosine	448:455	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	2	33	theme	surface	431:437	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	7	34	theme	aberrant	1641:1648	arg1	α2,6-sialylation					1650:1665	ST6Gal1-mediated aberrant α2,6-sialylation	1624:1665	ST6Gal1-mediated aberrant α2,6-sialylation	1624:1665	Overall, our data demonstrates that ST6Gal1-mediated aberrant α2,6-sialylation actively tunes the resistance of ErbB2-driven GC cells to trastuzumab.
33947960	3	35	theme	specific	651:658	arg1	signatures					676:685	specific aberrant glycan signatures	651:685	specific aberrant glycan signatures	651:685	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	2	36	theme	oncogenic	416:424	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	5	37	theme	glycosylation	1069:1081	arg1	profile					1083:1089	a site-specific glycosylation profile	1053:1089	a site-specific glycosylation profile	1053:1089	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	0	38	theme	site-specific	45:57	arg1	manner					59:64	a site-specific manner	43:64	a site-specific manner	43:64	ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab.
33947960	2	39	theme	target	349:354	arg1	epitope					356:362	Trastuzumab's target epitope	335:362	Trastuzumab's target epitope	335:362	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	5	40	theme	trastuzumab-binding	1224:1242	arg1	domain					1244:1249	the receptor's trastuzumab-binding domain	1209:1249	the receptor's trastuzumab-binding domain	1209:1249	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	1	41	theme	ErbB2-positive	224:237	arg1	GC					268:269	GC	268:269	GC	268:269	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	1	41	theme	ErbB2-positive	224:237	arg1	cancer					260:265	ErbB2-positive unresectable gastric cancer	224:265	ErbB2-positive unresectable gastric cancer (GC)	224:270	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	5	42	theme	ectodomain	1032:1041	arg1	analysis					1012:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis	951:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain	951:1041	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	3	43	theme	glycan	669:674	arg1	signatures					676:685	specific aberrant glycan signatures	651:685	specific aberrant glycan signatures	651:685	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	6	44	theme	EGFR	1577:1580	arg1	RTKs					1582:1585	both ErbB2 and EGFR RTKs	1562:1585	RTKs	1582:1585	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	1	45	theme	gastric	252:258	arg1	GC					268:269	GC	268:269	GC	268:269	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	1	45	theme	gastric	252:258	arg1	cancer					260:265	ErbB2-positive unresectable gastric cancer	224:265	ErbB2-positive unresectable gastric cancer (GC)	224:270	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	6	46	theme	receptor	1381:1388	arg1	half-life					1358:1366	the cellular half-life	1345:1366	the cellular half-life of the ErbB2 receptor	1345:1388	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	6	47	theme	ErbB2	1567:1571	arg1	RTKs					1582:1585	both ErbB2 and EGFR RTKs	1562:1585	RTKs	1582:1585	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	3	48	theme	cells	751:755	arg1	features					721:728	the malignant features	707:728	the malignant features	707:728	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	48	theme	cells	751:755	arg1	acquisition					772:782	the acquisition	768:782	the acquisition of trastuzumab resistance	768:808	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	1	49	theme	therapeutic	160:170	arg1	trastuzumab					192:202	the therapeutic monoclonal antibody trastuzumab	156:202	the therapeutic monoclonal antibody trastuzumab	156:202	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	1	50	theme	molecular	313:321	arg1	resistance					323:332	molecular resistance	313:332	molecular resistance	313:332	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	3	51	theme	ErbB2-addicted	733:746	arg1	cells					751:755	ErbB2-addicted GC cells	733:755	ErbB2-addicted GC cells	733:755	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	1	52	theme	antibody	183:190	arg1	trastuzumab					192:202	the therapeutic monoclonal antibody trastuzumab	156:202	the therapeutic monoclonal antibody trastuzumab	156:202	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	6	53	theme	trastuzumab-induced	1434:1452	arg1	cytotoxicity					1454:1465	trastuzumab-induced cytotoxicity	1434:1465	trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs	1434:1585	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	3	54	theme	site-specific	550:562	arg1	ErbB2					585:589	ErbB2	585:589	ErbB2	585:589	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	54	theme	site-specific	550:562	arg1	repertoire					571:580	the site-specific glycan repertoire	546:580	the site-specific glycan repertoire of ErbB2	546:589	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	4	55	theme	clinical	931:938	arg1	specimens					940:948	GC clinical specimens	928:948	GC clinical specimens	928:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	5	56	gly	N-glycosylation	1170:1184	arg2	sites					1186:1190	ErbB2 N-glycosylation sites	1164:1190	ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain	1164:1249	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	4	57	gly	α2,3-sialylated	891:905	arg1	structures					914:923	both α2,6- and α2,3-sialylated glycan structures	876:923	both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens	876:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	6	58	theme	ErbB2-dependent	1406:1420	arg1	cells					1425:1429	ErbB2-dependent GC cells	1406:1429	ErbB2-dependent GC cells	1406:1429	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	3	59	theme	ErbB2	585:589	arg1	mechanisms					626:635	the detailed molecular mechanisms	603:635	the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance	603:808	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	59	theme	ErbB2	585:589	arg1	repertoire					571:580	the site-specific glycan repertoire	546:580	the site-specific glycan repertoire of ErbB2	546:589	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	59	theme	ErbB2	585:589	arg1	ErbB2					585:589	ErbB2	585:589	ErbB2	585:589	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	4	60	theme	glycan	907:912	arg1	structures					914:923	both α2,6- and α2,3-sialylated glycan structures	876:923	both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens	876:948	Here, we demonstrate that ErbB2 is modified with both α2,6- and α2,3-sialylated glycan structures in GC clinical specimens.
33947960	3	61	theme	trastuzumab	787:797	arg1	resistance					799:808	trastuzumab resistance	787:808	trastuzumab resistance	787:808	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	62	theme	detailed	607:614	arg1	mechanisms					626:635	the detailed molecular mechanisms	603:635	the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance	603:808	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	7	63	theme	GC	1713:1714	arg1	cells					1716:1720	ErbB2-driven GC cells	1700:1720	ErbB2-driven GC cells	1700:1720	Overall, our data demonstrates that ST6Gal1-mediated aberrant α2,6-sialylation actively tunes the resistance of ErbB2-driven GC cells to trastuzumab.
33947960	6	64	from	membrane	1520:1527	arg1	stabilization					1479:1491	the stabilization	1475:1491	the stabilization of ErbB dimers at the cell membrane	1475:1527	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	6	64	from	membrane	1520:1527	arg1	activation					1548:1557	the decreased activation	1534:1557	the decreased activation of both ErbB2 and EGFR RTKs	1534:1585	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	1	65	theme	clinical	132:139	arg1	performance					141:151	The clinical performance	128:151	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC)	128:270	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	2	66	located	localized	367:375	arg1	domain					402:407	the extracellular domain	384:407	the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation	384:534	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	2	66	located	localized	367:375	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	2	66	located	localized	367:375	arg2	epitope					356:362	Trastuzumab's target epitope	335:362	Trastuzumab's target epitope	335:362	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	6	67	theme	expression	1274:1283	arg1	Abrogation					1252:1261	Abrogation	1252:1261	Abrogation of ST6Gal1 expression	1252:1283	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	6	68	theme	ErbB	1496:1499	arg1	dimers					1501:1506	ErbB dimers	1496:1506	ErbB dimers	1496:1506	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	0	69	theme	cancer	88:93	arg1	sensitivity					100:110	gastric cancer cell sensitivity	80:110	gastric cancer cell sensitivity	80:110	ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab.
33947960	5	70	theme	glycoproteomic	997:1010	arg1	analysis					1012:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis	951:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain	951:1041	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	2	71	theme	N-linked	513:520	arg1	glycosylation					522:534	extensive N-linked glycosylation	503:534	extensive N-linked glycosylation	503:534	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	1	72	from	performance	141:151	arg1	treatment					211:219	the treatment	207:219	the treatment of ErbB2-positive unresectable gastric cancer (GC)	207:270	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	5	73	theme	N-glycosylation	1170:1184	arg1	sites					1186:1190	ErbB2 N-glycosylation sites	1164:1190	ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain	1164:1249	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	5	74	theme	mass	960:963	arg1	analysis					1012:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis	951:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain	951:1041	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	2	75	theme	kinase	457:462	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	5	76	theme	glycomic	984:991	arg1	analysis					1012:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis	951:1019	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain	951:1041	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	2	77	theme	receptor	439:446	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	2	78	theme	cell	426:429	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	0	79	theme	ErbB2	34:38	arg1	ErbB2					34:38	ErbB2	34:38	ErbB2	34:38	ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab.
33947960	0	79	theme	ErbB2	34:38	arg1	ectodomain					20:29	the ectodomain	16:29	the ectodomain of ErbB2	16:38	ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab.
33947960	5	80	theme	site-specific	1055:1067	arg1	profile					1083:1089	a site-specific glycosylation profile	1053:1089	a site-specific glycosylation profile	1053:1089	In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain.
33947960	2	81	theme	ErbB2	470:474	arg1	domain					402:407	the extracellular domain	384:407	the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation	384:534	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	2	81	theme	ErbB2	470:474	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	6	82	theme	cell	1515:1518	arg1	membrane					1520:1527	the cell membrane	1511:1527	the cell membrane	1511:1527	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	7	83	theme	ST6Gal1-mediated	1624:1639	arg1	α2,6-sialylation					1650:1665	ST6Gal1-mediated aberrant α2,6-sialylation	1624:1665	ST6Gal1-mediated aberrant α2,6-sialylation	1624:1665	Overall, our data demonstrates that ST6Gal1-mediated aberrant α2,6-sialylation actively tunes the resistance of ErbB2-driven GC cells to trastuzumab.
33947960	2	84	theme	RTK	465:467	arg1	ErbB2					470:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2	412:474	Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation.
33947960	1	85	theme	resistance	323:332	arg1	emergence					300:308	the emergence	296:308	the emergence of molecular resistance	296:332	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	3	86	theme	aberrant	660:667	arg1	signatures					676:685	specific aberrant glycan signatures	651:685	specific aberrant glycan signatures	651:685	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	6	87	theme	RTKs	1582:1585	arg1	stabilization					1479:1491	the stabilization	1475:1491	the stabilization of ErbB dimers at the cell membrane	1475:1527	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	6	87	theme	RTKs	1582:1585	arg1	activation					1548:1557	the decreased activation	1534:1557	the decreased activation of both ErbB2 and EGFR RTKs	1534:1585	Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs.
33947960	1	88	theme	unresectable	239:250	arg1	GC					268:269	GC	268:269	GC	268:269	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	1	88	theme	unresectable	239:250	arg1	cancer					260:265	ErbB2-positive unresectable gastric cancer	224:265	ErbB2-positive unresectable gastric cancer (GC)	224:270	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
33947960	3	89	theme	malignant	711:719	arg1	features					721:728	the malignant features	707:728	the malignant features	707:728	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	3	89	theme	malignant	711:719	arg1	acquisition					772:782	the acquisition	768:782	the acquisition of trastuzumab resistance	768:808	However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive.
33947960	1	90	theme	cancer	260:265	arg1	treatment					211:219	the treatment	207:219	the treatment of ErbB2-positive unresectable gastric cancer (GC)	207:270	The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance.
32559081	0	0	theme	Viral	80:84	arg1	Membrane					86:93	a Viral Membrane	78:93	a Viral Membrane	78:93	Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane.
32559081	1	1	gly	glycosylated	171:182	arg1	protein					217:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	5	2	theme	viral	873:877	arg1	membrane					879:886	a viral membrane	871:886	a viral membrane	871:886	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	2	3	dep	PDB	267:269	arg1	PDB					267:269	PDB	267:269	PDB: 6VSB and 6VXX	267:284	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	2	3	dep	PDB	267:269	arg1	6VXX					281:284	6VXX	281:284	6VXX	281:284	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	2	3	dep	PDB	267:269	arg1	6VSB					272:275	6VSB	272:275	6VSB	272:275	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	4	4	gly	glycosylated	633:644	arg1	structures					674:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	6	5	theme	COVID-19	1196:1203	arg1	treatment					1183:1191	treatment	1183:1191	treatment	1183:1191	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	6	5	theme	COVID-19	1196:1203	arg1	prevention					1168:1177	prevention	1168:1177	prevention	1168:1177	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	6	6	theme	COVID-19	986:993	arg1	Archive					995:1001	CHARMM-GUI COVID-19 Archive	975:1001	CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19	975:1203	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	6	6	theme	COVID-19	986:993	arg1	http					1004:1007	http://www.charmm-gui.org/docs/archive/covid19	1004:1049	http://www.charmm-gui.org/docs/archive/covid19	1004:1049	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	6	7	theme	CHARMM-GUI	975:984	arg1	Archive					995:1001	CHARMM-GUI COVID-19 Archive	975:1001	CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19	975:1203	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	6	7	theme	CHARMM-GUI	975:984	arg1	http					1004:1007	http://www.charmm-gui.org/docs/archive/covid19	1004:1049	http://www.charmm-gui.org/docs/archive/covid19	1004:1049	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	5	8	theme	molecular	911:919	arg1	simulations					930:940	all-atom molecular dynamics simulations	902:940	all-atom molecular dynamics simulations	902:940	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	4	9	theme	model	668:672	arg1	structures					674:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	5	10	theme	Membrane	827:834	arg1	Builder					836:842	CHARMM-GUI Membrane Builder	816:842	CHARMM-GUI Membrane Builder	816:842	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	4	11	from	data	746:749	arg1	maps					784:787	their respective experimental maps	754:787	their respective experimental maps using ISOLDE	754:800	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	4	12	theme	respective	760:769	arg1	maps					784:787	their respective experimental maps	754:787	their respective experimental maps using ISOLDE	754:800	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	4	13	theme	full-length	646:656	arg1	structures					674:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	2	14	theme	protein	372:378	arg1	prediction					390:399	de-novo protein structure prediction	364:399	de-novo protein structure prediction	364:399	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	2	15	theme	GALAXY	434:439	arg1	suite					450:454	GALAXY modeling suite	434:454	GALAXY modeling suite	434:454	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	6	16	theme	modeling	1127:1134	arg1	research					1151:1158	innovative and novel modeling and simulation research	1106:1158	innovative and novel modeling and simulation research for the prevention and treatment of COVID-19	1106:1203	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	1	17	theme	glycosylated	171:182	arg1	protein					217:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	5	18	theme	dynamics	921:928	arg1	simulations					930:940	all-atom molecular dynamics simulations	902:940	all-atom molecular dynamics simulations	902:940	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	1	19	theme	full-length	184:194	arg1	protein					217:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	6	20	from	Archive	995:1001	arg1	available					962:970	available	962:970	available	962:970	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	1	21	theme	SARS-CoV-2	196:205	arg1	protein					217:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	2	22	theme	modeling	411:418	arg1	techniques					420:429	loop modeling techniques	406:429	loop modeling techniques	406:429	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	4	23	theme	low-resolution	731:744	arg1	data					746:749	the low-resolution data	727:749	the low-resolution data in their respective experimental maps using ISOLDE	727:800	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	1	24	theme	spike	207:211	arg1	protein					217:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	2	25	theme	loop	406:409	arg1	techniques					420:429	loop modeling techniques	406:429	loop modeling techniques	406:429	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	1	26	theme	technical	101:109	arg1	study					111:115	This technical study	96:115	This technical study	96:115	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	4	27	theme	protein	660:666	arg1	structures					674:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	0	28	theme	SARS-CoV-2	44:53	arg1	Model					69:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane.
32559081	6	29	dep	prevention	1168:1177	arg1	the					1164:1166	the	1164:1166	the	1164:1166	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	4	30	theme	glycosylated	633:644	arg1	structures					674:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	1	31	theme	S	214:214	arg1	protein					217:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	a fully glycosylated full-length SARS-CoV-2 spike (S) protein	163:223	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	0	32	theme	Full-Length	32:42	arg1	Model					69:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane.
32559081	5	33	theme	S	857:857	arg1	proteins					859:866	the S proteins	853:866	the S proteins	853:866	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	0	34	theme	Glycosylated	19:30	arg1	Model					69:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane.
32559081	6	35	from	available	962:970	arg1	Archive					995:1001	CHARMM-GUI COVID-19 Archive	975:1001	CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19	975:1203	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	6	35	from	available	962:970	arg1	http					1004:1007	http://www.charmm-gui.org/docs/archive/covid19	1004:1049	http://www.charmm-gui.org/docs/archive/covid19	1004:1049	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	2	36	theme	structure	380:388	arg1	prediction					390:399	de-novo protein structure prediction	364:399	de-novo protein structure prediction	364:399	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	0	37	theme	Protein	61:67	arg1	Model					69:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane.
32559081	5	38	used	used	811:814	arg2	We					803:804	We	803:804	We	803:804	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	6	39	theme	simulation	1140:1149	arg1	research					1151:1158	innovative and novel modeling and simulation research	1106:1158	innovative and novel modeling and simulation research for the prevention and treatment of COVID-19	1106:1203	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	0	40	theme	Spike	55:59	arg1	Model					69:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model	11:73	Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane.
32559081	3	41	theme	monomer	555:561	arg1	N-glycans					522:530	22 N-glycans	519:530	22 N-glycans	519:530	Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI.
32559081	3	41	theme	monomer	555:561	arg1	O-glycan					538:545	1 O-glycan	536:545	1 O-glycan	536:545	Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI.
32559081	3	42	theme	determined	482:491	arg1	glycoforms					507:516	the recently determined most occupied glycoforms	469:516	the recently determined most occupied glycoforms	469:516	Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI.
32559081	2	43	theme	protein	301:307	arg1	structures					309:318	full-length S protein structures	287:318	full-length S protein structures	287:318	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	4	44	theme	S	658:658	arg1	structures					674:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures	621:683	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	1	45	theme	all-atom	127:134	arg1	modeling					136:143	all-atom modeling and simulation	127:158	modeling	136:143	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	6	46	theme	novel	1121:1125	arg1	modeling					1127:1134	novel modeling	1121:1134	novel modeling	1121:1134	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	1	47	theme	protein	217:223	arg1	simulation					149:158	all-atom modeling and simulation	127:158	simulation	149:158	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	1	47	theme	protein	217:223	arg1	modeling					136:143	all-atom modeling and simulation	127:158	modeling	136:143	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
32559081	5	48	theme	all-atom	902:909	arg1	simulations					930:940	all-atom molecular dynamics simulations	902:940	all-atom molecular dynamics simulations	902:940	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	4	49	theme	experimental	771:782	arg1	maps					784:787	their respective experimental maps	754:787	their respective experimental maps using ISOLDE	754:800	These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE.
32559081	2	50	theme	full-length	287:297	arg1	structures					309:318	full-length S protein structures	287:318	full-length S protein structures	287:318	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	2	51	theme	S	299:299	arg1	structures					309:318	full-length S protein structures	287:318	full-length S protein structures	287:318	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	6	52	theme	innovative	1106:1115	arg1	research					1151:1158	innovative and novel modeling and simulation research	1106:1158	innovative and novel modeling and simulation research for the prevention and treatment of COVID-19	1106:1203	All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
32559081	5	53	theme	CHARMM-GUI	816:825	arg1	Builder					836:842	CHARMM-GUI Membrane Builder	816:842	CHARMM-GUI Membrane Builder	816:842	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	2	54	theme	template-based	339:352	arg1	modeling					354:361	template-based modeling	339:361	template-based modeling	339:361	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	2	55	theme	de-novo	364:370	arg1	prediction					390:399	de-novo protein structure prediction	364:399	de-novo protein structure prediction	364:399	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	2	56	theme	modeling	441:448	arg1	suite					450:454	GALAXY modeling suite	434:454	GALAXY modeling suite	434:454	First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite.
32559081	5	57	from	place	847:851	arg1	membrane					879:886	a viral membrane	871:886	a viral membrane	871:886	We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations.
32559081	3	58	theme	occupied	498:505	arg1	glycoforms					507:516	the recently determined most occupied glycoforms	469:516	the recently determined most occupied glycoforms	469:516	Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI.
32559081	1	59	theme	viral	230:234	arg1	membrane					236:243	a viral membrane	228:243	a viral membrane	228:243	This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane.
31967800	2	0	theme	value	511:515	arg1	plus					517:520	a central value plus	501:520	a central value plus	501:520	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	1	1	theme	peptide	364:370	arg1	backbones					372:380	peptide backbones	364:380	peptide backbones	364:380	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	2	theme	spectrum-level	925:938	arg1	FDR					940:942	spectrum-level FDR	925:942	spectrum-level FDR ≤ 1%	925:947	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	3	theme	%	792:792	arg1	combination					767:777	the combination	763:777	the combination of 20%/30%/30%	763:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	3	theme	%	792:792	arg1	%					819:819	better than 20%/30%/40%	797:819	better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively	797:1162	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	0	4	theme	Collisional	90:100	arg1	Dissociation					102:113	Higher-Energy Collisional Dissociation	76:113	Higher-Energy Collisional Dissociation	76:113	New Energy Setup Strategy for Intact N-Glycopeptides Characterization Using Higher-Energy Collisional Dissociation.
31967800	3	5	theme	1771	1137:1140	arg1	%					1134:1134	97%	1132:1134	97% (1771 → 3495)	1132:1148	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	5	theme	1771	1137:1140	arg1	→					1142:1142	1771 → 3495	1137:1147	1771 → 3495	1137:1147	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	2	6	dep	energies	626:633	arg1	%					645:645	20%/30%/40%	635:645	the energies 20%/30%/40%	622:645	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	3	7	theme	total	910:914	arg1	IDs					916:918	total IDs	910:918	total IDs with spectrum-level FDR ≤ 1%	910:947	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	8	theme	gastric	886:892	arg1	tissues					901:907	gastric cancer tissues	886:907	gastric cancer tissues	886:907	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	9	gly	N-glycopeptides	856:870	arg2	N-glycopeptides					856:870	complex intact N-glycopeptides	841:870	complex intact N-glycopeptides enriched from gastric cancer tissues	841:907	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	4	10	theme	N-glycoproteomics	1206:1222	arg1	studies					1224:1230	all the coming N-glycoproteomics studies	1191:1230	all the coming N-glycoproteomics studies using HCD as the dissociation method	1191:1267	This finding will benefit all the coming N-glycoproteomics studies using HCD as the dissociation method.
31967800	3	11	theme	complex	841:847	arg1	N-glycopeptides					856:870	complex intact N-glycopeptides	841:870	complex intact N-glycopeptides enriched from gastric cancer tissues	841:907	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	12	theme	N-glycan	386:393	arg1	moieties					395:402	N-glycan moieties	386:402	N-glycan moieties	386:402	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	13	theme	N-glycopeptides	856:870	arg1	analysis					829:836	the analysis	825:836	the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues	825:907	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	14	dep	%	819:819	arg1	increased					1077:1085	increased	1077:1085	were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively	1072:1162	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	4	15	theme	coming	1199:1204	arg1	studies					1224:1230	all the coming N-glycoproteomics studies	1191:1230	all the coming N-glycoproteomics studies using HCD as the dissociation method	1191:1267	This finding will benefit all the coming N-glycoproteomics studies using HCD as the dissociation method.
31967800	2	16	theme	variation	530:538	arg1	setting					490:496	a dependent setting	478:496	a dependent setting of a central value plus minus a variation	478:538	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	2	16	theme	variation	530:538	arg1	available					543:551	available	543:551	available	543:551	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	2	17	theme	%	612:612	arg1	combination					590:600	the combination	586:600	the combination of 30 ± 10% to give the energies 20%/30%/40%	586:645	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	3	18	with	IDs	964:966	arg1	ions					1067:1070	structure-diagnostic fragment ions	1037:1070	structure-diagnostic fragment ions	1037:1070	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	18	with	IDs	964:966	arg1	FDR					940:942	spectrum-level FDR	925:942	spectrum-level FDR ≤ 1%	925:947	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	18	with	IDs	964:966	arg1	ions					999:1002	site-determining fragment ions	973:1002	site-determining fragment ions	973:1002	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	2	19	theme	dependent	480:488	arg1	setting					490:496	a dependent setting	478:496	a dependent setting of a central value plus minus a variation	478:538	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	2	19	theme	dependent	480:488	arg1	available					543:551	available	543:551	available	543:551	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	2	20	theme	central	503:509	arg1	plus					517:520	a central value plus	501:520	a central value plus	501:520	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	1	21	with	method	306:311	arg1	setting					134:140	the optional setting	121:140	the optional setting of multiple stepped collisional energies (NCEs)	121:188	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	22	theme	fragment	1058:1065	arg1	ions					1067:1070	structure-diagnostic fragment ions	1037:1070	structure-diagnostic fragment ions	1037:1070	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	0	23	theme	Energy	4:9	arg1	Strategy					17:24	New Energy Setup Strategy	0:24	New Energy Setup Strategy for Intact N-Glycopeptides Characterization	0:68	New Energy Setup Strategy for Intact N-Glycopeptides Characterization Using Higher-Energy Collisional Dissociation.
31967800	1	24	from	NCEs	447:450	arg1	fragmented					420:429	fragmented	420:429	fragmented	420:429	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	2	25	theme	±	608:608	arg1	%					612:612	30 ± 10%	605:612	30 ± 10% to give the energies 20%/30%/40%	605:645	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	2	26	theme	/30	638:640	arg1	%					645:645	20%/30%/40%	635:645	the energies 20%/30%/40%	622:645	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	1	27	theme	higher-energy	191:203	arg1	method					306:311	a widely adopted dissociation method	276:311	a widely adopted dissociation method	276:311	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	27	theme	higher-energy	191:203	arg1	HCD					231:233	HCD	231:233	HCD	231:233	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	27	theme	higher-energy	191:203	arg1	dissociation					217:228	higher-energy collisional dissociation	191:228	higher-energy collisional dissociation (HCD) as available on Orbitrap instruments	191:271	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	0	28	theme	New	0:2	arg1	Strategy					17:24	New Energy Setup Strategy	0:24	New Energy Setup Strategy for Intact N-Glycopeptides Characterization	0:68	New Energy Setup Strategy for Intact N-Glycopeptides Characterization Using Higher-Energy Collisional Dissociation.
31967800	1	29	theme	adopted	285:291	arg1	method					306:311	a widely adopted dissociation method	276:311	a widely adopted dissociation method	276:311	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	29	theme	adopted	285:291	arg1	dissociation					217:228	higher-energy collisional dissociation	191:228	higher-energy collisional dissociation (HCD) as available on Orbitrap instruments	191:271	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	2	30	theme	%	637:637	arg1	%					645:645	20%/30%/40%	635:645	the energies 20%/30%/40%	622:645	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	3	31	theme	%	815:815	arg1	%					819:819	better than 20%/30%/40%	797:819	better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively	797:1162	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	31	theme	%	815:815	arg1	combination					767:777	the combination	763:777	the combination of 20%/30%/30%	763:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	32	theme	collisional	205:215	arg1	method					306:311	a widely adopted dissociation method	276:311	a widely adopted dissociation method	276:311	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	32	theme	collisional	205:215	arg1	HCD					231:233	HCD	231:233	HCD	231:233	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	32	theme	collisional	205:215	arg1	dissociation					217:228	higher-energy collisional dissociation	191:228	higher-energy collisional dissociation (HCD) as available on Orbitrap instruments	191:271	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	2	33	dep	%	612:612	arg1	give					617:620	give	617:620	to give the energies 20%/30%/40%	614:645	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	1	34	theme	dissociation	293:304	arg1	method					306:311	a widely adopted dissociation method	276:311	a widely adopted dissociation method	276:311	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	34	theme	dissociation	293:304	arg1	dissociation					217:228	higher-energy collisional dissociation	191:228	higher-energy collisional dissociation (HCD) as available on Orbitrap instruments	191:271	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	4	35	theme	dissociation	1249:1260	arg1	method					1262:1267	the dissociation method	1245:1267	the dissociation method	1245:1267	This finding will benefit all the coming N-glycoproteomics studies using HCD as the dissociation method.
31967800	4	35	theme	dissociation	1249:1260	arg1	HCD					1238:1240	HCD	1238:1240	HCD	1238:1240	This finding will benefit all the coming N-glycoproteomics studies using HCD as the dissociation method.
31967800	0	36	theme	Setup	11:15	arg1	Strategy					17:24	New Energy Setup Strategy	0:24	New Energy Setup Strategy for Intact N-Glycopeptides Characterization	0:68	New Energy Setup Strategy for Intact N-Glycopeptides Characterization Using Higher-Energy Collisional Dissociation.
31967800	3	37	theme	site-determining	973:988	arg1	ions					999:1002	site-determining fragment ions	973:1002	site-determining fragment ions	973:1002	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	38	theme	optional	125:132	arg1	setting					134:140	the optional setting	121:140	the optional setting of multiple stepped collisional energies (NCEs)	121:188	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	39	theme	%	811:811	arg1	%					819:819	better than 20%/30%/40%	797:819	better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively	797:1162	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	39	theme	%	811:811	arg1	combination					767:777	the combination	763:777	the combination of 20%/30%/30%	763:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	40	with	IDs	916:918	arg1	ions					1067:1070	structure-diagnostic fragment ions	1037:1070	structure-diagnostic fragment ions	1037:1070	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	40	with	IDs	916:918	arg1	FDR					940:942	spectrum-level FDR	925:942	spectrum-level FDR ≤ 1%	925:947	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	40	with	IDs	916:918	arg1	ions					999:1002	site-determining fragment ions	973:1002	site-determining fragment ions	973:1002	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	0	41	theme	Intact	30:35	arg1	Characterization					53:68	Intact N-Glycopeptides Characterization	30:68	Intact N-Glycopeptides Characterization	30:68	New Energy Setup Strategy for Intact N-Glycopeptides Characterization Using Higher-Energy Collisional Dissociation.
31967800	3	42	theme	site-specific	950:962	arg1	IDs					964:966	site-specific IDs	950:966	site-specific IDs with site-determining fragment ions	950:1002	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	43	theme	/30	785:787	arg1	%					792:792	20%/30%/30%	782:792	20%/30%/30%	782:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	44	theme	/30	812:814	arg1	%					819:819	better than 20%/30%/40%	797:819	better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively	797:1162	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	44	theme	/30	812:814	arg1	combination					767:777	the combination	763:777	the combination of 20%/30%/30%	763:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	45	theme	intact	317:322	arg1	characterization					340:355	intact N-glycopeptides characterization	317:355	intact N-glycopeptides characterization	317:355	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	46	theme	high	434:437	arg1	NCEs					447:450	high and low NCEs	434:450	high and low NCEs	434:450	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	47	theme	N-glycopeptides	324:338	arg1	characterization					340:355	intact N-glycopeptides characterization	317:355	intact N-glycopeptides characterization	317:355	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	48	theme	structure-diagnostic	1037:1056	arg1	ions					1067:1070	structure-diagnostic fragment ions	1037:1070	structure-diagnostic fragment ions	1037:1070	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	0	49	theme	N-Glycopeptides	37:51	arg1	Characterization					53:68	Intact N-Glycopeptides Characterization	30:68	Intact N-Glycopeptides Characterization	30:68	New Energy Setup Strategy for Intact N-Glycopeptides Characterization Using Higher-Energy Collisional Dissociation.
31967800	3	50	theme	structure-specific	1009:1026	arg1	IDs					1028:1030	structure-specific IDs	1009:1030	structure-specific IDs with structure-diagnostic fragment ions	1009:1070	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	51	theme	low	443:445	arg1	NCEs					447:450	high and low NCEs	434:450	high and low NCEs	434:450	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	52	theme	recent	699:704	arg1	availability					706:717	the recent availability	695:717	the recent availability of an independent NCEs setup	695:746	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	53	theme	fragment	990:997	arg1	ions					999:1002	site-determining fragment ions	973:1002	site-determining fragment ions	973:1002	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	2	54	theme	%	641:641	arg1	%					645:645	20%/30%/40%	635:645	the energies 20%/30%/40%	622:645	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	1	55	theme	multiple	145:152	arg1	energies					174:181	multiple stepped collisional energies	145:181	multiple stepped collisional energies (NCEs)	145:188	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	55	theme	multiple	145:152	arg1	NCEs					184:187	NCEs	184:187	NCEs	184:187	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	56	theme	%	784:784	arg1	%					792:792	20%/30%/30%	782:792	20%/30%/30%	782:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	57	theme	setup	742:746	arg1	availability					706:717	the recent availability	695:717	the recent availability of an independent NCEs setup	695:746	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	58	with	IDs	1028:1030	arg1	ions					1067:1070	structure-diagnostic fragment ions	1037:1070	structure-diagnostic fragment ions	1037:1070	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	58	with	IDs	1028:1030	arg1	FDR					940:942	spectrum-level FDR	925:942	spectrum-level FDR ≤ 1%	925:947	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	58	with	IDs	1028:1030	arg1	ions					999:1002	site-determining fragment ions	973:1002	site-determining fragment ions	973:1002	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	59	gly	N-glycopeptides	324:338	arg2	N-glycopeptides					324:338	intact N-glycopeptides characterization	317:355	intact N-glycopeptides characterization	317:355	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	60	theme	stepped	154:160	arg1	energies					174:181	multiple stepped collisional energies	145:181	multiple stepped collisional energies (NCEs)	145:188	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	60	theme	stepped	154:160	arg1	NCEs					184:187	NCEs	184:187	NCEs	184:187	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	61	theme	available	239:247	arg1	method					306:311	a widely adopted dissociation method	276:311	a widely adopted dissociation method	276:311	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	61	theme	available	239:247	arg1	HCD					231:233	HCD	231:233	HCD	231:233	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	61	theme	available	239:247	arg1	dissociation					217:228	higher-energy collisional dissociation	191:228	higher-energy collisional dissociation (HCD) as available on Orbitrap instruments	191:271	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	0	62	theme	Higher-Energy	76:88	arg1	Dissociation					102:113	Higher-Energy Collisional Dissociation	76:113	Higher-Energy Collisional Dissociation	76:113	New Energy Setup Strategy for Intact N-Glycopeptides Characterization Using Higher-Energy Collisional Dissociation.
31967800	3	63	theme	%	788:788	arg1	%					792:792	20%/30%/30%	782:792	20%/30%/30%	782:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	64	theme	intact	849:854	arg1	N-glycopeptides					856:870	complex intact N-glycopeptides	841:870	complex intact N-glycopeptides enriched from gastric cancer tissues	841:907	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	65	theme	collisional	162:172	arg1	energies					174:181	multiple stepped collisional energies	145:181	multiple stepped collisional energies (NCEs)	145:188	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	1	65	theme	collisional	162:172	arg1	NCEs					184:187	NCEs	184:187	NCEs	184:187	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	66	theme	cancer	894:899	arg1	tissues					901:907	gastric cancer tissues	886:907	gastric cancer tissues	886:907	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	3	67	theme	independent	725:735	arg1	setup					742:746	an independent NCEs setup	722:746	an independent NCEs setup	722:746	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	2	68	theme	plus	517:520	arg1	setting					490:496	a dependent setting	478:496	a dependent setting of a central value plus minus a variation	478:538	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	2	68	theme	plus	517:520	arg1	available					543:551	available	543:551	available	543:551	Initially, a dependent setting of a central value plus minus a variation is available to the users to set up NCEs, and the combination of 30 ± 10% to give the energies 20%/30%/40% has been mostly adopted in the literature.
31967800	3	69	theme	NCEs	737:740	arg1	setup					742:746	an independent NCEs setup	722:746	an independent NCEs setup	722:746	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	70	theme	energies	174:181	arg1	setting					134:140	the optional setting	121:140	the optional setting of multiple stepped collisional energies (NCEs)	121:188	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
31967800	3	71	theme	/30	789:791	arg1	%					792:792	20%/30%/30%	782:792	20%/30%/30%	782:792	With the recent availability of an independent NCEs setup, we found that the combination of 20%/30%/30% is better than 20%/30%/40%; in the analysis of complex intact N-glycopeptides enriched from gastric cancer tissues, total IDs with spectrum-level FDR ≤ 1%, site-specific IDs with site-determining fragment ions, and structure-specific IDs with structure-diagnostic fragment ions were increased by 42% (4,767 → 6,746), 57% (599 → 942), and 97% (1771 → 3495), respectively.
31967800	1	72	theme	Orbitrap	252:259	arg1	instruments					261:271	Orbitrap instruments	252:271	Orbitrap instruments	252:271	With the optional setting of multiple stepped collisional energies (NCEs), higher-energy collisional dissociation (HCD) as available on Orbitrap instruments is a widely adopted dissociation method for intact N-glycopeptides characterization, where peptide backbones and N-glycan moieties are selectively fragmented at high and low NCEs, respectively.
32938717	8	0	theme	substrates	1568:1577	arg1	toolbox					1548:1554	This toolbox	1543:1554	This toolbox of mutants, substrates, and methods	1543:1590	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	7	1	theme	enzymatic	1376:1384	arg1	properties					1386:1395	different enzymatic properties	1366:1395	different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit	1366:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	3	2	theme	mutated	553:559	arg1	OSTs					561:564	mutated OSTs	553:564	mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3	553:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	8	3	theme	basis	1643:1647	arg1	investigations					1611:1624	investigations	1611:1624	investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms	1611:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	8	4	theme	physiological	1653:1665	arg1	roles					1667:1671	physiological roles	1653:1671	physiological roles of the OST enzymes in yeast and other organisms	1653:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	7	5	theme	OST	1400:1402	arg1	complexes					1404:1412	OST complexes	1400:1412	OST complexes containing either the Ost3 or Ost6 subunit	1400:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	6	6	theme	opposite	1187:1194	arg1	effect					1196:1201	the opposite effect	1183:1201	the opposite effect	1183:1201	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	3	7	theme	high-affinity	574:586	arg1	tag					596:598	a high-affinity epitope tag	572:598	a high-affinity epitope tag attached to the catalytic subunit Stt3	572:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	0	8	link	lipid-linked	29:40	arg1	oligosaccharide					42:56	lipid-linked oligosaccharide	29:56	lipid-linked oligosaccharide from the oligosaccharyl transfer reaction	29:98	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	8	9	theme	OST	1680:1682	arg1	enzymes					1684:1690	the OST enzymes	1676:1690	the OST enzymes	1676:1690	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	5	10	theme	Stt3	837:840	arg1	subunit					842:848	the Stt3 subunit	833:848	the Stt3 subunit	833:848	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	0	11	from	reaction	91:98	arg1	hydrolysis					15:24	the hydrolysis	11:24	the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase	11:152	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	0	11	from	reaction	91:98	arg1	oligosaccharide					42:56	lipid-linked oligosaccharide	29:56	lipid-linked oligosaccharide from the oligosaccharyl transfer reaction	29:98	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	7	12	theme	mutated	1325:1331	arg1	OSTs					1333:1336	the mutated OSTs	1321:1336	the mutated OSTs	1321:1336	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	8	13	from	organisms	1711:1719	arg1	investigations					1611:1624	investigations	1611:1624	investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms	1611:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	5	14	from	subunit	842:848	arg1	effects					809:815	the effects	805:815	the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro	805:889	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	14	from	subunit	842:848	arg1	effects					909:915	their effects	903:915	their effects on the N-glycan attachment and FNG content levels in yeast cells	903:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	4	15	theme	purified	705:712	arg1	useful					744:749	useful	744:749	useful	744:749	The purified OST protein with mutations is useful for wide-ranging biochemical experiments.
32938717	4	15	theme	purified	705:712	arg1	protein					718:724	The purified OST protein	701:724	The purified OST protein with mutations	701:739	The purified OST protein with mutations is useful for wide-ranging biochemical experiments.
32938717	6	16	theme	activities	1230:1239	arg1	decoupling					1208:1217	the decoupling	1204:1217	the decoupling of the two activities	1204:1239	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	0	17	theme	oligosaccharyl	67:80	arg1	reaction					91:98	the oligosaccharyl transfer reaction	63:98	the oligosaccharyl transfer reaction	63:98	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	3	18	theme	catalytic	616:624	arg1	Stt3					634:637	the catalytic subunit Stt3	612:637	the catalytic subunit Stt3	612:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	7	19	theme	shorter	1525:1531	arg1	peptides					1533:1540	shorter peptides	1525:1540	shorter peptides	1525:1540	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	0	20	from	hydrolysis	15:24	arg1	reaction					91:98	the oligosaccharyl transfer reaction	63:98	the oligosaccharyl transfer reaction	63:98	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	1	21	link	N-linked	228:235	arg1	glycosylation					237:249	the N-linked glycosylation	224:249	the N-linked glycosylation	224:249	Oligosaccharyltransferase (OST) is responsible for the first step in the N-linked glycosylation, transferring an oligosaccharide chain onto asparagine residues to create glycoproteins.
32938717	6	22	from	mutations	997:1005	arg1	motif					1024:1028	the first DXD motif	1010:1028	the first DXD motif	1010:1028	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	4	23	theme	wide-ranging	755:766	arg1	experiments					780:790	wide-ranging biochemical experiments	755:790	wide-ranging biochemical experiments	755:790	The purified OST protein with mutations is useful for wide-ranging biochemical experiments.
32938717	0	24	theme	point	103:107	arg1	mutations					109:117	point mutations	103:117	point mutations in yeast oligosaccharyltransferase	103:152	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	5	25	from	mutations	820:828	arg1	subunit					842:848	the Stt3 subunit	833:848	the Stt3 subunit	833:848	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	26	theme	FNG	948:950	arg1	content					952:958	FNG content	948:958	FNG content	948:958	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	2	27	theme	free	434:437	arg1	FNGs					450:453	FNGs	450:453	FNGs	450:453	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	2	27	theme	free	434:437	arg1	N-glycans					439:447	free N-glycans	434:447	free N-glycans (FNGs)	434:454	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	6	28	theme	mechanism	1293:1301	arg1	deconvolution					1263:1275	future deconvolution	1256:1275	future deconvolution of the reaction mechanism	1256:1301	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	5	29	from	effects	809:815	arg1	subunit					842:848	the Stt3 subunit	833:848	the Stt3 subunit	833:848	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	29	from	effects	809:815	arg1	levels					960:965	the N-glycan attachment and FNG content levels	920:965	the N-glycan attachment and FNG content levels in yeast cells	920:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	29	from	effects	809:815	arg1	activities					871:880	the two enzymatic activities	853:880	the two enzymatic activities	853:880	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	8	30	from	investigations	1611:1624	arg1	yeast					1695:1699	yeast	1695:1699	yeast	1695:1699	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	8	30	from	investigations	1611:1624	arg1	organisms					1711:1719	other organisms	1705:1719	other organisms	1705:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	8	31	theme	other	1705:1709	arg1	organisms					1711:1719	other organisms	1705:1719	other organisms	1705:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	7	32	dep	Ost3	1436:1439	arg1	the					1432:1434	the	1432:1434	the	1432:1434	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	7	33	theme	15-residue	1471:1480	arg1	substrate					1510:1518	a better-quality substrate	1493:1518	a better-quality substrate than shorter peptides	1493:1540	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	7	33	theme	15-residue	1471:1480	arg1	peptide					1482:1488	a 15-residue peptide	1469:1488	a 15-residue peptide	1469:1488	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	5	34	theme	attachment	933:942	arg1	levels					960:965	the N-glycan attachment and FNG content levels	920:965	the N-glycan attachment and FNG content levels in yeast cells	920:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	6	35	theme	first	1014:1018	arg1	motif					1024:1028	the first DXD motif	1010:1028	the first DXD motif	1010:1028	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	8	36	theme	molecular	1633:1641	arg1	basis					1643:1647	the molecular basis	1629:1647	the molecular basis	1629:1647	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	0	37	theme	lipid-linked	29:40	arg1	oligosaccharide					42:56	lipid-linked oligosaccharide	29:56	lipid-linked oligosaccharide from the oligosaccharyl transfer reaction	29:98	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	2	38	theme	endoplasmic	478:488	arg1	ER					501:502	ER	501:502	ER	501:502	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	2	38	theme	endoplasmic	478:488	arg1	reticulum					490:498	the endoplasmic reticulum	474:498	the endoplasmic reticulum (ER)	474:503	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	8	39	from	basis	1643:1647	arg1	yeast					1695:1699	yeast	1695:1699	yeast	1695:1699	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	8	39	from	basis	1643:1647	arg1	organisms					1711:1719	other organisms	1705:1719	other organisms	1705:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	6	40	theme	transfer	1099:1106	arg1	activity					1108:1115	the oligosaccharyl transfer activity	1080:1115	the oligosaccharyl transfer activity	1080:1115	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	2	41	theme	acceptor	361:368	arg1	asparagine					370:379	an acceptor asparagine	358:379	an acceptor asparagine	358:379	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	8	42	theme	methods	1584:1590	arg1	toolbox					1548:1554	This toolbox	1543:1554	This toolbox of mutants, substrates, and methods	1543:1590	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	7	43	theme	Ost6	1444:1447	arg1	subunit					1449:1455	either the Ost3 or Ost6 subunit	1425:1455	either the Ost3 or Ost6 subunit	1425:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	5	44	theme	yeast	970:974	arg1	cells					976:980	yeast cells	970:980	yeast cells	970:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	2	45	theme	oligosaccharide	401:415	arg1	donor					417:421	the oligosaccharide donor	397:421	the oligosaccharide donor	397:421	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	7	46	theme	Ost3	1436:1439	arg1	subunit					1449:1455	either the Ost3 or Ost6 subunit	1425:1455	either the Ost3 or Ost6 subunit	1425:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	6	47	theme	relative	1068:1075	arg1	activity					1059:1066	the FNG generation activity	1040:1066	the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo	1040:1142	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	5	48	from	levels	960:965	arg1	cells					976:980	yeast cells	970:980	yeast cells	970:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	6	49	theme	generation	1048:1057	arg1	activity					1059:1066	the FNG generation activity	1040:1066	the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo	1040:1142	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	1	50	theme	asparagine	295:304	arg1	residues					306:313	asparagine residues	295:313	asparagine residues	295:313	Oligosaccharyltransferase (OST) is responsible for the first step in the N-linked glycosylation, transferring an oligosaccharide chain onto asparagine residues to create glycoproteins.
32938717	3	51	theme	purification	529:540	arg1	method					542:547	a purification method	527:547	a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3	527:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	1	52	theme	first	210:214	arg1	step					216:219	the first step	206:219	the first step in the N-linked glycosylation	206:249	Oligosaccharyltransferase (OST) is responsible for the first step in the N-linked glycosylation, transferring an oligosaccharide chain onto asparagine residues to create glycoproteins.
32938717	7	53	theme	different	1366:1374	arg1	properties					1386:1395	different enzymatic properties	1366:1395	different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit	1366:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	8	54	from	yeast	1695:1699	arg1	investigations					1611:1624	investigations	1611:1624	investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms	1611:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	5	55	theme	enzymatic	861:869	arg1	activities					871:880	the two enzymatic activities	853:880	the two enzymatic activities	853:880	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	6	56	theme	reaction	1284:1291	arg1	mechanism					1293:1301	the reaction mechanism	1280:1301	the reaction mechanism	1280:1301	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	8	57	theme	roles	1667:1671	arg1	investigations					1611:1624	investigations	1611:1624	investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms	1611:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	1	58	theme	N-linked	228:235	arg1	glycosylation					237:249	the N-linked glycosylation	224:249	the N-linked glycosylation	224:249	Oligosaccharyltransferase (OST) is responsible for the first step in the N-linked glycosylation, transferring an oligosaccharide chain onto asparagine residues to create glycoproteins.
32938717	7	59	theme	OSTs	1333:1336	arg1	isolation					1308:1316	The isolation	1304:1316	The isolation of the mutated OSTs	1304:1336	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	6	60	theme	future	1256:1261	arg1	deconvolution					1263:1275	future deconvolution	1256:1275	future deconvolution of the reaction mechanism	1256:1301	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	3	61	theme	epitope	588:594	arg1	tag					596:598	a high-affinity epitope tag	572:598	a high-affinity epitope tag attached to the catalytic subunit Stt3	572:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	8	62	theme	enzymes	1684:1690	arg1	basis					1643:1647	the molecular basis	1629:1647	the molecular basis	1629:1647	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	8	62	theme	enzymes	1684:1690	arg1	roles					1667:1671	physiological roles	1653:1671	physiological roles of the OST enzymes in yeast and other organisms	1653:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	6	63	theme	DK	1170:1171	arg1	motif					1173:1177	the DK motif	1166:1177	the DK motif	1166:1177	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	3	64	theme	subunit	626:632	arg1	Stt3					634:637	the catalytic subunit Stt3	612:637	the catalytic subunit Stt3	612:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	1	65	gly	glycoproteins	325:337	arg1	glycoproteins					325:337	glycoproteins	325:337	glycoproteins	325:337	Oligosaccharyltransferase (OST) is responsible for the first step in the N-linked glycosylation, transferring an oligosaccharide chain onto asparagine residues to create glycoproteins.
32938717	7	66	contain	containing	1414:1423	arg1	complexes					1404:1412	OST complexes	1400:1412	OST complexes containing either the Ost3 or Ost6 subunit	1400:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	7	66	contain	containing	1414:1423	arg2	subunit					1449:1455	either the Ost3 or Ost6 subunit	1425:1455	either the Ost3 or Ost6 subunit	1425:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	0	67	from	mutations	109:117	arg1	oligosaccharyltransferase					128:152	yeast oligosaccharyltransferase	122:152	yeast oligosaccharyltransferase	122:152	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	4	68	theme	OST	714:716	arg1	useful					744:749	useful	744:749	useful	744:749	The purified OST protein with mutations is useful for wide-ranging biochemical experiments.
32938717	4	68	theme	OST	714:716	arg1	protein					718:724	The purified OST protein	701:724	The purified OST protein with mutations	701:739	The purified OST protein with mutations is useful for wide-ranging biochemical experiments.
32938717	0	69	theme	transfer	82:89	arg1	reaction					91:98	the oligosaccharyl transfer reaction	63:98	the oligosaccharyl transfer reaction	63:98	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	1	70	from	step	216:219	arg1	glycosylation					237:249	the N-linked glycosylation	224:249	the N-linked glycosylation	224:249	Oligosaccharyltransferase (OST) is responsible for the first step in the N-linked glycosylation, transferring an oligosaccharide chain onto asparagine residues to create glycoproteins.
32938717	5	71	dep	attachment	933:942	arg1	the					920:922	the	920:922	the	920:922	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	6	72	from	mutations	1153:1161	arg1	motif					1173:1177	the DK motif	1166:1177	the DK motif	1166:1177	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	3	73	attach	attached	600:607	arg2	tag					596:598	a high-affinity epitope tag	572:598	a high-affinity epitope tag attached to the catalytic subunit Stt3	572:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	3	73	attach	attached	600:607	arg1	Stt3					634:637	the catalytic subunit Stt3	612:637	the catalytic subunit Stt3	612:637	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	7	74	theme	better-quality	1495:1508	arg1	substrate					1510:1518	a better-quality substrate	1493:1518	a better-quality substrate than shorter peptides	1493:1540	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	7	74	theme	better-quality	1495:1508	arg1	peptide					1482:1488	a 15-residue peptide	1469:1488	a 15-residue peptide	1469:1488	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	7	75	from	properties	1386:1395	arg1	complexes					1404:1412	OST complexes	1400:1412	OST complexes containing either the Ost3 or Ost6 subunit	1400:1455	The isolation of the mutated OSTs also enabled us to identify different enzymatic properties in OST complexes containing either the Ost3 or Ost6 subunit and to find a 15-residue peptide as a better-quality substrate than shorter peptides.
32938717	0	76	theme	yeast	122:126	arg1	oligosaccharyltransferase					128:152	yeast oligosaccharyltransferase	122:152	yeast oligosaccharyltransferase	122:152	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	5	77	theme	content	952:958	arg1	levels					960:965	the N-glycan attachment and FNG content levels	920:965	the N-glycan attachment and FNG content levels in yeast cells	920:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	6	78	theme	FNG	1044:1046	arg1	activity					1059:1066	the FNG generation activity	1040:1066	the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo	1040:1142	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	4	79	theme	biochemical	768:778	arg1	experiments					780:790	wide-ranging biochemical experiments	755:790	wide-ranging biochemical experiments	755:790	The purified OST protein with mutations is useful for wide-ranging biochemical experiments.
32938717	5	80	from	effects	909:915	arg1	subunit					842:848	the Stt3 subunit	833:848	the Stt3 subunit	833:848	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	80	from	effects	909:915	arg1	activities					871:880	the two enzymatic activities	853:880	the two enzymatic activities	853:880	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	80	from	effects	909:915	arg1	levels					960:965	the N-glycan attachment and FNG content levels	920:965	the N-glycan attachment and FNG content levels in yeast cells	920:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	81	theme	mutations	820:828	arg1	effects					809:815	the effects	805:815	the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro	805:889	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	81	theme	mutations	820:828	arg1	effects					909:915	their effects	903:915	their effects on the N-glycan attachment and FNG content levels in yeast cells	903:980	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	5	82	theme	N-glycan	924:931	arg1	attachment					933:942	N-glycan attachment	924:942	N-glycan attachment	924:942	We assessed the effects of mutations in the Stt3 subunit on the two enzymatic activities in vitro, as well as their effects on the N-glycan attachment and FNG content levels in yeast cells.
32938717	6	83	theme	DXD	1020:1022	arg1	motif					1024:1028	the first DXD motif	1010:1028	the first DXD motif	1010:1028	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	6	84	contain	had	1179:1181	arg1	mutations					1153:1161	mutations	1153:1161	mutations in the DK motif	1153:1177	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	6	84	contain	had	1179:1181	arg2	effect					1196:1201	the opposite effect	1183:1201	the opposite effect	1183:1201	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	3	85	theme	yeast	645:649	arg1	cells					651:655	yeast cells	645:655	yeast cells co-expressing the WT OST to support growth	645:698	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	2	86	dep	asparagine	370:379	arg1	the					343:345	the	343:345	the	343:345	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	2	86	dep	asparagine	370:379	arg1	absence					347:353	absence	347:353	absence	347:353	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	0	87	theme	oligosaccharide	42:56	arg1	hydrolysis					15:24	the hydrolysis	11:24	the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase	11:152	Uncoupling the hydrolysis of lipid-linked oligosaccharide from the oligosaccharyl transfer reaction by point mutations in yeast oligosaccharyltransferase.
32938717	2	88	theme	reticulum	490:498	arg1	lumen					465:469	the lumen	461:469	the lumen of the endoplasmic reticulum (ER)	461:503	In the absence of an acceptor asparagine, OST hydrolyzes the oligosaccharide donor, releasing free N-glycans (FNGs) into the lumen of the endoplasmic reticulum (ER).
32938717	3	89	theme	WT	675:676	arg1	OST					678:680	the WT OST	671:680	the WT OST to support growth	671:698	Here, we established a purification method for mutated OSTs using a high-affinity epitope tag attached to the catalytic subunit Stt3, from yeast cells co-expressing the WT OST to support growth.
32938717	6	90	theme	oligosaccharyl	1084:1097	arg1	activity					1108:1115	the oligosaccharyl transfer activity	1080:1115	the oligosaccharyl transfer activity	1080:1115	We found that mutations in the first DXD motif increased the FNG generation activity relative to the oligosaccharyl transfer activity, both in vitro and in vivo, whereas mutations in the DK motif had the opposite effect; the decoupling of the two activities may facilitate future deconvolution of the reaction mechanism.
32938717	8	91	theme	mutants	1559:1565	arg1	toolbox					1548:1554	This toolbox	1543:1554	This toolbox of mutants, substrates, and methods	1543:1590	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	4	92	with	protein	718:724	arg1	mutations					731:739	mutations	731:739	mutations	731:739	The purified OST protein with mutations is useful for wide-ranging biochemical experiments.
32938717	8	93	from	roles	1667:1671	arg1	yeast					1695:1699	yeast	1695:1699	yeast	1695:1699	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	8	93	from	roles	1667:1671	arg1	organisms					1711:1719	other organisms	1705:1719	other organisms	1705:1719	This toolbox of mutants, substrates, and methods will be useful for investigations of the molecular basis and physiological roles of the OST enzymes in yeast and other organisms.
32938717	1	94	theme	oligosaccharide	268:282	arg1	chain					284:288	an oligosaccharide chain	265:288	an oligosaccharide chain onto asparagine residues to create glycoproteins	265:337	Oligosaccharyltransferase (OST) is responsible for the first step in the N-linked glycosylation, transferring an oligosaccharide chain onto asparagine residues to create glycoproteins.
33908015	3	0	theme	native	336:341	arg1	glycans					343:349	native glycans	336:349	native glycans	336:349	Analysis of native glycans is not very sensitive due to the low ionization efficiency of glycans.
33908015	4	1	theme	sensitive	519:527	arg1	techniques					542:551	sensitive and reliable techniques	519:551	sensitive and reliable techniques	519:551	These facts necessitate their comprehensive structural studies and establishes a high demand for sensitive and reliable techniques.
33908015	8	2	theme	graphitized	1098:1108	arg1	carbon					1110:1115	porous graphitized carbon	1091:1115	porous graphitized carbon	1091:1115	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	8	2	theme	graphitized	1098:1108	arg1	PGC					1086:1088	PGC	1086:1088	PGC (porous graphitized carbon) column	1086:1123	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	3	3	theme	glycans	343:349	arg1	Analysis					324:331	Analysis	324:331	Analysis of native glycans	324:349	Analysis of native glycans is not very sensitive due to the low ionization efficiency of glycans.
33908015	6	4	gly	glycoproteins	744:756	arg1	glycoproteins					744:756	model glycoproteins	738:756	model glycoproteins	738:756	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	7	5	theme	sialic	1024:1029	arg1	residues					1036:1043	sialic acid residues	1024:1043	sialic acid residues	1024:1043	We introduce protein extraction and release of glycans, followed by strategies to purify the released glycans, which are reduced and permethylated to improve ionization efficiency and stabilize sialic acid residues.
33908015	8	6	from	separation	1072:1081	arg1	column					1118:1123	PGC (porous graphitized carbon) column	1086:1123	PGC (porous graphitized carbon) column	1086:1123	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	7	7	theme	released	923:930	arg1	glycans					932:938	the released glycans	919:938	the released glycans	919:938	We introduce protein extraction and release of glycans, followed by strategies to purify the released glycans, which are reduced and permethylated to improve ionization efficiency and stabilize sialic acid residues.
33908015	4	8	theme	reliable	533:540	arg1	techniques					542:551	sensitive and reliable techniques	519:551	sensitive and reliable techniques	519:551	These facts necessitate their comprehensive structural studies and establishes a high demand for sensitive and reliable techniques.
33908015	7	9	theme	acid	1031:1034	arg1	residues					1036:1043	sialic acid residues	1024:1043	sialic acid residues	1024:1043	We introduce protein extraction and release of glycans, followed by strategies to purify the released glycans, which are reduced and permethylated to improve ionization efficiency and stabilize sialic acid residues.
33908015	4	10	theme	high	503:506	arg1	demand					508:513	a high demand	501:513	a high demand for sensitive and reliable techniques	501:551	These facts necessitate their comprehensive structural studies and establishes a high demand for sensitive and reliable techniques.
33908015	6	11	attach	derived	725:731	arg2	glycans					717:723	permethylated glycans	703:723	permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS,	703:813	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	6	11	attach	derived	725:731	arg1	samples					781:787	complex biological samples	762:787	complex biological samples	762:787	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	6	11	attach	derived	725:731	arg1	glycoproteins					744:756	model glycoproteins	738:756	model glycoproteins	738:756	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	8	12	theme	LC-based	1063:1070	arg1	separation					1072:1081	High-temperature LC-based separation	1046:1081	High-temperature LC-based separation on PGC (porous graphitized carbon) column	1046:1123	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	6	13	theme	biological	770:779	arg1	samples					781:787	complex biological samples	762:787	complex biological samples	762:787	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	5	14	theme	isomeric	658:665	arg1	glycans					667:673	permethylated isomeric glycans	644:673	permethylated isomeric glycans	644:673	In this chapter, we discuss the strategies for effective separation and identification of permethylated isomeric glycans.
33908015	5	15	theme	permethylated	644:656	arg1	glycans					667:673	permethylated isomeric glycans	644:673	permethylated isomeric glycans	644:673	In this chapter, we discuss the strategies for effective separation and identification of permethylated isomeric glycans.
33908015	2	16	theme	various	294:300	arg1	diseases					302:309	various diseases	294:309	various diseases	294:309	Their altered expression has been associated with various diseases and cancers.
33908015	6	17	theme	complex	762:768	arg1	samples					781:787	complex biological samples	762:787	complex biological samples	762:787	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	5	18	theme	glycans	667:673	arg1	identification					626:639	identification	626:639	identification	626:639	In this chapter, we discuss the strategies for effective separation and identification of permethylated isomeric glycans.
33908015	5	18	theme	glycans	667:673	arg1	separation					611:620	effective separation	601:620	effective separation	601:620	In this chapter, we discuss the strategies for effective separation and identification of permethylated isomeric glycans.
33908015	7	19	theme	ionization	988:997	arg1	efficiency					999:1008	ionization efficiency	988:1008	ionization efficiency	988:1008	We introduce protein extraction and release of glycans, followed by strategies to purify the released glycans, which are reduced and permethylated to improve ionization efficiency and stabilize sialic acid residues.
33908015	3	20	theme	ionization	388:397	arg1	efficiency					399:408	the low ionization efficiency	380:408	the low ionization efficiency of glycans	380:419	Analysis of native glycans is not very sensitive due to the low ionization efficiency of glycans.
33908015	1	21	from	existence	119:127	arg1	forms					152:156	isomeric forms	143:156	isomeric forms	143:156	The existence of glycans in isomeric forms is responsible for the multifariousness of their properties and biological functions.
33908015	6	22	theme	model	738:742	arg1	glycoproteins					744:756	model glycoproteins	738:756	model glycoproteins	738:756	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	8	23	theme	porous	1091:1096	arg1	carbon					1110:1115	porous graphitized carbon	1091:1115	porous graphitized carbon	1091:1115	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	8	23	theme	porous	1091:1096	arg1	PGC					1086:1088	PGC	1086:1088	PGC (porous graphitized carbon) column	1086:1123	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	0	24	theme	Glycan	26:31	arg1	Structures					33:42	Isomeric Glycan Structures	17:42	Isomeric Glycan Structures	17:42	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).
33908015	5	25	theme	effective	601:609	arg1	separation					611:620	effective separation	601:620	effective separation	601:620	In this chapter, we discuss the strategies for effective separation and identification of permethylated isomeric glycans.
33908015	8	26	theme	High-temperature	1046:1061	arg1	separation					1072:1081	High-temperature LC-based separation	1046:1081	High-temperature LC-based separation on PGC (porous graphitized carbon) column	1046:1123	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	3	27	theme	low	384:386	arg1	efficiency					399:408	the low ionization efficiency	380:408	the low ionization efficiency of glycans	380:419	Analysis of native glycans is not very sensitive due to the low ionization efficiency of glycans.
33908015	8	28	theme	isomeric	1141:1148	arg1	separation					1150:1159	isomeric separation	1141:1159	isomeric separation of glycans	1141:1170	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	7	29	theme	glycans	877:883	arg1	release					866:872	release	866:872	release of glycans	866:883	We introduce protein extraction and release of glycans, followed by strategies to purify the released glycans, which are reduced and permethylated to improve ionization efficiency and stabilize sialic acid residues.
33908015	7	29	theme	glycans	877:883	arg1	extraction					851:860	protein extraction	843:860	protein extraction	843:860	We introduce protein extraction and release of glycans, followed by strategies to purify the released glycans, which are reduced and permethylated to improve ionization efficiency and stabilize sialic acid residues.
33908015	1	30	theme	properties	207:216	arg1	multifariousness					181:196	the multifariousness	177:196	the multifariousness of their properties and biological functions	177:241	The existence of glycans in isomeric forms is responsible for the multifariousness of their properties and biological functions.
33908015	8	31	theme	glycans	1164:1170	arg1	separation					1150:1159	isomeric separation	1141:1159	isomeric separation of glycans	1141:1170	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	4	32	theme	structural	466:475	arg1	studies					477:483	their comprehensive structural studies	446:483	their comprehensive structural studies	446:483	These facts necessitate their comprehensive structural studies and establishes a high demand for sensitive and reliable techniques.
33908015	2	33	theme	altered	250:256	arg1	expression					258:267	Their altered expression	244:267	Their altered expression	244:267	Their altered expression has been associated with various diseases and cancers.
33908015	0	34	theme	Structures	33:42	arg1	Determination					0:12	Determination	0:12	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).	0:113	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).
33908015	1	35	theme	biological	222:231	arg1	functions					233:241	biological functions	222:241	biological functions	222:241	The existence of glycans in isomeric forms is responsible for the multifariousness of their properties and biological functions.
33908015	7	36	theme	protein	843:849	arg1	extraction					851:860	protein extraction	843:860	protein extraction	843:860	We introduce protein extraction and release of glycans, followed by strategies to purify the released glycans, which are reduced and permethylated to improve ionization efficiency and stabilize sialic acid residues.
33908015	3	37	theme	glycans	413:419	arg1	efficiency					399:408	the low ionization efficiency	380:408	the low ionization efficiency of glycans	380:419	Analysis of native glycans is not very sensitive due to the low ionization efficiency of glycans.
33908015	6	38	theme	permethylated	703:715	arg1	glycans					717:723	permethylated glycans	703:723	permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS,	703:813	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	8	39	theme	PGC	1086:1088	arg1	column					1118:1123	PGC (porous graphitized carbon) column	1086:1123	PGC (porous graphitized carbon) column	1086:1123	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	8	40	theme	sensitive	1189:1197	arg1	identification					1199:1212	their sensitive identification	1183:1212	their sensitive identification	1183:1212	High-temperature LC-based separation on PGC (porous graphitized carbon) column is conducive to isomeric separation of glycans and allows their sensitive identification and quantification using MS/MS.
33908015	1	41	theme	glycans	132:138	arg1	existence					119:127	The existence	115:127	The existence of glycans in isomeric forms	115:156	The existence of glycans in isomeric forms is responsible for the multifariousness of their properties and biological functions.
33908015	1	41	theme	glycans	132:138	arg1	responsible					161:171	responsible	161:171	responsible	161:171	The existence of glycans in isomeric forms is responsible for the multifariousness of their properties and biological functions.
33908015	1	42	theme	functions	233:241	arg1	multifariousness					181:196	the multifariousness	177:196	the multifariousness of their properties and biological functions	177:241	The existence of glycans in isomeric forms is responsible for the multifariousness of their properties and biological functions.
33908015	4	43	theme	comprehensive	452:464	arg1	studies					477:483	their comprehensive structural studies	446:483	their comprehensive structural studies	446:483	These facts necessitate their comprehensive structural studies and establishes a high demand for sensitive and reliable techniques.
33908015	0	44	theme	Chromatography-Mass	73:91	arg1	Spectrometry					93:104	Liquid Chromatography-Mass Spectrometry	66:104	Liquid Chromatography-Mass Spectrometry (LC-MS)	66:112	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).
33908015	0	44	theme	Chromatography-Mass	73:91	arg1	LC-MS					107:111	LC-MS	107:111	LC-MS	107:111	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).
33908015	1	45	theme	isomeric	143:150	arg1	forms					152:156	isomeric forms	143:156	isomeric forms	143:156	The existence of glycans in isomeric forms is responsible for the multifariousness of their properties and biological functions.
33908015	6	46	theme	sample	680:685	arg1	preparation					687:697	The sample preparation	676:697	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS,	676:813	The sample preparation for permethylated glycans derived from model glycoproteins and complex biological samples, analyzed using LC-MS/MS, is delineated.
33908015	0	47	theme	Liquid	66:71	arg1	Spectrometry					93:104	Liquid Chromatography-Mass Spectrometry	66:104	Liquid Chromatography-Mass Spectrometry (LC-MS)	66:112	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).
33908015	0	47	theme	Liquid	66:71	arg1	LC-MS					107:111	LC-MS	107:111	LC-MS	107:111	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).
33908015	0	48	theme	Isomeric	17:24	arg1	Structures					33:42	Isomeric Glycan Structures	17:42	Isomeric Glycan Structures	17:42	Determination of Isomeric Glycan Structures by Permethylation and Liquid Chromatography-Mass Spectrometry (LC-MS).
32298658	5	0	theme	oligomannose	767:778	arg1	levels					780:785	oligomannose levels	767:785	oligomannose levels	767:785	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	3	1	theme	significant	538:548	arg1	proportions					550:560	significant proportions	538:560	significant proportions of high-mannose type N-linked glycans	538:598	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	8	2	theme	HA	1202:1203	arg1	glycosylation					1205:1217	HA glycosylation	1202:1217	HA glycosylation	1202:1217	These findings reveal the biological significance of HA glycosylation and therapeutic potential of targeting these structures.
32298658	0	3	theme	Potent	94:99	arg1	Neutralization					101:114	Potent Neutralization	94:114	Potent Neutralization by Lectins	94:125	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	6	4	theme	H1N1	976:979	arg1	strains					990:996	human H1N1 and H3N2 strains	970:996	human H1N1 and H3N2 strains	970:996	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	1	5	from	viruses	170:176	arg1	Hemagglutinins					128:141	Hemagglutinins	128:141	Hemagglutinins (HAs) from human influenza viruses	128:176	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	1	6	theme	α2-3	280:283	arg1	specificity					285:295	the α2-3 specificity	276:295	the α2-3 specificity of avian virus progenitors	276:322	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	6	7	theme	human	970:974	arg1	strains					990:996	human H1N1 and H3N2 strains	970:996	human H1N1 and H3N2 strains	970:996	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	7	8	theme	broad	1066:1070	arg1	capacity					1072:1079	a broad capacity	1064:1079	a broad capacity to neutralize and prevent infection with contemporary H3N2 strains	1064:1146	Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains.
32298658	6	9	gly	glycosites	946:955	arg2	glycosites					946:955	high-mannose glycosites	933:955	high-mannose glycosites	933:955	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	3	10	theme	glycans	592:598	arg1	proportions					550:560	significant proportions	538:560	significant proportions of high-mannose type N-linked glycans	538:598	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	3	11	link	N-linked	583:590	arg1	glycans					592:598	high-mannose type N-linked glycans	565:598	high-mannose type N-linked glycans	565:598	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	0	12	contain	Contain	37:43	arg2	Glycans					77:83	Conserved Oligomannose N-Linked Glycans	45:83	Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins	45:125	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	0	12	contain	Contain	37:43	arg1	Hemagglutinins					22:35	Human Influenza Virus Hemagglutinins	0:35	Human Influenza Virus Hemagglutinins	0:35	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	7	13	theme	high-mannose-binding	1027:1046	arg1	lectins					1048:1054	high-mannose-binding lectins	1027:1054	high-mannose-binding lectins	1027:1054	Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains.
32298658	2	14	theme	gain	357:360	arg1	sites					376:380	gain glycosylation sites	357:380	gain glycosylation sites	357:380	Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined.
32298658	1	15	link	α2-6-linked	192:202	arg1	sialosides					204:213	α2-6-linked sialosides	192:213	α2-6-linked sialosides	192:213	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	8	16	theme	therapeutic	1223:1233	arg1	potential					1235:1243	therapeutic potential	1223:1243	therapeutic potential	1223:1243	These findings reveal the biological significance of HA glycosylation and therapeutic potential of targeting these structures.
32298658	3	17	theme	type	578:581	arg1	glycans					592:598	high-mannose type N-linked glycans	565:598	high-mannose type N-linked glycans	565:598	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	3	18	theme	glycomic	466:473	arg1	analysis					475:482	quantitative glycomic analysis	453:482	quantitative glycomic analysis	453:482	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	7	19	with	infection	1107:1115	arg1	strains					1140:1146	contemporary H3N2 strains	1122:1146	contemporary H3N2 strains	1122:1146	Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains.
32298658	3	20	theme	N-linked	583:590	arg1	glycans					592:598	high-mannose type N-linked glycans	565:598	high-mannose type N-linked glycans	565:598	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	0	21	theme	Influenza	6:14	arg1	Virus					16:20	Human Influenza Virus	0:20	Human Influenza Virus Hemagglutinins	0:35	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	3	22	theme	high-mannose	565:576	arg1	glycans					592:598	high-mannose type N-linked glycans	565:598	high-mannose type N-linked glycans	565:598	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	8	23	theme	potential	1235:1243	arg1	significance					1186:1197	the biological significance	1171:1197	the biological significance of HA glycosylation and therapeutic potential of targeting these structures	1171:1273	These findings reveal the biological significance of HA glycosylation and therapeutic potential of targeting these structures.
32298658	1	24	theme	α2-6-linked	192:202	arg1	sialosides					204:213	α2-6-linked sialosides	192:213	α2-6-linked sialosides	192:213	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	0	25	theme	Human	0:4	arg1	Virus					16:20	Human Influenza Virus	0:20	Human Influenza Virus Hemagglutinins	0:35	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	1	26	theme	avian	300:304	arg1	progenitors					312:322	avian virus progenitors	300:322	avian virus progenitors	300:322	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	6	27	theme	strains	990:996	arg1	HA					964:965	the HA	960:965	the HA of human H1N1 and H3N2 strains	960:996	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	6	28	from	positions	920:928	arg1	HA					964:965	the HA	960:965	the HA of human H1N1 and H3N2 strains	960:996	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	2	29	theme	biological	408:417	arg1	function					419:426	their biological function	402:426	their biological function	402:426	Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined.
32298658	1	30	theme	virus	306:310	arg1	progenitors					312:322	avian virus progenitors	300:322	avian virus progenitors	300:322	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	1	31	from	specificity	285:295	arg1	distinct					262:269	distinct	262:269	distinct	262:269	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	5	32	located	present	802:808	arg2	they					793:796	they	793:796	they	793:796	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	5	32	located	present	802:808	arg1	all					813:815	all	813:815	all	813:815	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	4	33	theme	complex-type	695:706	arg1	glycans					708:714	predominately complex-type glycans	681:714	predominately complex-type glycans	681:714	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	0	34	theme	Virus	16:20	arg1	Hemagglutinins					22:35	Human Influenza Virus Hemagglutinins	0:35	Human Influenza Virus Hemagglutinins	0:35	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	1	35	theme	progenitors	312:322	arg1	specificity					285:295	the α2-3 specificity	276:295	the α2-3 specificity of avian virus progenitors	276:322	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	6	36	theme	glycosites	946:955	arg1	positions					920:928	The positions	916:928	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains	916:996	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	3	37	theme	head	615:618	arg1	domain					620:625	the head domain	611:625	the head domain	611:625	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	0	38	theme	Conserved	45:53	arg1	Glycans					77:83	Conserved Oligomannose N-Linked Glycans	45:83	Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins	45:125	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	4	39	theme	structural	736:745	arg1	diversity					747:755	greater structural diversity	728:755	greater structural diversity	728:755	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	5	40	from	all	813:815	arg1	present					802:808	present	802:808	present	802:808	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	4	41	theme	greater	728:734	arg1	diversity					747:755	greater structural diversity	728:755	greater structural diversity	728:755	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	3	42	theme	quantitative	453:464	arg1	analysis					475:482	quantitative glycomic analysis	453:482	quantitative glycomic analysis	453:482	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	5	43	dep	recombinant	824:834	arg1	HAs					836:838	HAs	836:838	HAs	836:838	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	5	43	dep	recombinant	824:834	arg1	viruses					850:856	viruses	850:856	viruses	850:856	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	1	44	theme	receptor-defined	229:244	arg1	barrier					254:260	a receptor-defined species barrier	227:260	a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors	227:322	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	0	45	theme	N-Linked	68:75	arg1	Glycans					77:83	Conserved Oligomannose N-Linked Glycans	45:83	Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins	45:125	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	7	46	theme	contemporary	1122:1133	arg1	strains					1140:1146	contemporary H3N2 strains	1122:1146	contemporary H3N2 strains	1122:1146	Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains.
32298658	5	47	from	present	802:808	arg1	all					813:815	all	813:815	all	813:815	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	0	48	theme	Oligomannose	55:66	arg1	Glycans					77:83	Conserved Oligomannose N-Linked Glycans	45:83	Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins	45:125	Human Influenza Virus Hemagglutinins Contain Conserved Oligomannose N-Linked Glycans Allowing Potent Neutralization by Lectins.
32298658	7	49	theme	H3N2	1135:1138	arg1	strains					1140:1146	contemporary H3N2 strains	1122:1146	contemporary H3N2 strains	1122:1146	Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains.
32298658	2	50	contain	HAs	353:355	arg1	human-adapted					339:351	human-adapted	339:351	human-adapted	339:351	Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined.
32298658	2	50	contain	HAs	353:355	arg2	sites					376:380	gain glycosylation sites	357:380	gain glycosylation sites	357:380	Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined.
32298658	8	51	theme	glycosylation	1205:1217	arg1	significance					1186:1197	the biological significance	1171:1197	the biological significance of HA glycosylation and therapeutic potential of targeting these structures	1171:1273	These findings reveal the biological significance of HA glycosylation and therapeutic potential of targeting these structures.
32298658	2	52	theme	glycosylation	362:374	arg1	sites					376:380	gain glycosylation sites	357:380	gain glycosylation sites	357:380	Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined.
32298658	1	53	theme	species	246:252	arg1	barrier					254:260	a receptor-defined species barrier	227:260	a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors	227:322	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	2	54	gly	glycosylation	362:374	arg2	sites					376:380	gain glycosylation sites	357:380	gain glycosylation sites	357:380	Additionally, human-adapted HAs gain glycosylation sites over time, although their biological function is poorly defined.
32298658	4	55	dep	avian-origin	656:667	arg1	HAs					669:671	HAs	669:671	HAs	669:671	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	4	56	contain	contain	673:679	arg1	avian-origin					656:667	avian-origin	656:667	avian-origin	656:667	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	4	56	contain	contain	673:679	arg2	glycans					708:714	predominately complex-type glycans	681:714	predominately complex-type glycans	681:714	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	5	57	attach	present	802:808	arg2	they					793:796	they	793:796	they	793:796	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	5	57	attach	present	802:808	arg1	all					813:815	all	813:815	all	813:815	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	1	58	dep	Hemagglutinins	128:141	arg1	HAs					144:146	HAs	144:146	HAs	144:146	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	3	59	theme	human	507:511	arg1	viruses					522:528	human pandemic viruses	507:528	human pandemic viruses	507:528	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	6	60	theme	high-mannose	933:944	arg1	glycosites					946:955	high-mannose glycosites	933:955	high-mannose glycosites	933:955	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	4	61	contain	have	723:726	arg1	glycans					708:714	predominately complex-type glycans	681:714	predominately complex-type glycans	681:714	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	4	61	contain	have	723:726	arg2	diversity					747:755	greater structural diversity	728:755	greater structural diversity	728:755	By contrast, poorly adapted avian-origin HAs contain predominately complex-type glycans, which have greater structural diversity.
32298658	5	62	theme	universal	895:903	arg1	detection					905:913	universal detection	895:913	universal detection	895:913	Although oligomannose levels vary, they are present in all tested recombinant HAs and whole viruses and can be specifically targeted for universal detection.
32298658	1	63	theme	human	154:158	arg1	viruses					170:176	human influenza viruses	154:176	human influenza viruses	154:176	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	3	64	theme	pandemic	513:520	arg1	viruses					522:528	human pandemic viruses	507:528	human pandemic viruses	507:528	Using quantitative glycomic analysis, we show that HAs from human pandemic viruses exhibit significant proportions of high-mannose type N-linked glycans throughout the head domain.
32298658	1	65	theme	distinct	262:269	arg1	barrier					254:260	a receptor-defined species barrier	227:260	a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors	227:322	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	7	66	contain	possess	1056:1062	arg2	capacity					1072:1079	a broad capacity	1064:1079	a broad capacity to neutralize and prevent infection with contemporary H3N2 strains	1064:1146	Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains.
32298658	7	66	contain	possess	1056:1062	arg1	lectins					1048:1054	high-mannose-binding lectins	1027:1054	high-mannose-binding lectins	1027:1054	Additionally, high-mannose-binding lectins possess a broad capacity to neutralize and prevent infection with contemporary H3N2 strains.
32298658	6	67	theme	H3N2	985:988	arg1	strains					990:996	human H1N1 and H3N2 strains	970:996	human H1N1 and H3N2 strains	970:996	The positions of high-mannose glycosites on the HA of human H1N1 and H3N2 strains are conserved.
32298658	1	68	theme	influenza	160:168	arg1	viruses					170:176	human influenza viruses	154:176	human influenza viruses	154:176	Hemagglutinins (HAs) from human influenza viruses adapt to bind α2-6-linked sialosides, overcoming a receptor-defined species barrier distinct from the α2-3 specificity of avian virus progenitors.
32298658	8	69	theme	biological	1175:1184	arg1	significance					1186:1197	the biological significance	1171:1197	the biological significance of HA glycosylation and therapeutic potential of targeting these structures	1171:1273	These findings reveal the biological significance of HA glycosylation and therapeutic potential of targeting these structures.
33462887	0	0	theme	Digestion	82:90	arg1	Combination					57:67	a Combination	55:67	a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry	55:125	Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry.
33462887	5	1	theme	ion	785:787	arg1	spectrometry					803:814	ion mobility mass spectrometry	785:814	ion mobility mass spectrometry	785:814	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	1	2	gly	glycosylated	180:191	arg1	proteins					193:200	glycosylated proteins	180:200	glycosylated proteins	180:200	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	2	3	theme	glycosylation	354:366	arg1	effects					343:349	the effects	339:349	the effects of glycosylation on the folding and stability of DC-SIGN	339:406	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	0	4	theme	Enzymatic	72:80	arg1	Digestion					82:90	Enzymatic Digestion	72:90	Enzymatic Digestion	72:90	Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry.
33462887	5	5	theme	collision	916:924	arg1	section					932:938	the overall collision cross section	904:938	the overall collision cross section	904:938	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	3	6	theme	approach	511:518	arg1	application					470:480	application	470:480	application	470:480	Herein, we report the development and application of a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN.
33462887	3	6	theme	approach	511:518	arg1	development					454:464	development	454:464	development	454:464	Herein, we report the development and application of a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN.
33462887	0	7	theme	Ion	96:98	arg1	Spectrometry					114:125	Ion Mobility Mass Spectrometry	96:125	Ion Mobility Mass Spectrometry	96:125	Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry.
33462887	5	8	theme	isoforms	983:990	arg1	stability					958:966	the gas-phase stability	944:966	the gas-phase stability of the DC-SIGN isoforms	944:990	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	5	8	theme	isoforms	983:990	arg1	section					932:938	the overall collision cross section	904:938	the overall collision cross section	904:938	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	4	9	theme	exoglycosidase	752:765	arg1	sequencing					767:776	sequential exoglycosidase sequencing	741:776	sequential exoglycosidase sequencing	741:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	10	theme	sequential	741:750	arg1	sequencing					767:776	sequential exoglycosidase sequencing	741:776	sequential exoglycosidase sequencing	741:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	2	11	from	effects	343:349	arg1	stability					387:395	stability	387:395	stability	387:395	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	2	11	from	effects	343:349	arg1	folding					375:381	folding	375:381	folding	375:381	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	3	12	theme	mass-spectrometry-based	487:509	arg1	approach					511:518	a mass-spectrometry-based approach	485:518	a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN	485:604	Herein, we report the development and application of a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN.
33462887	5	13	theme	gas-phase	948:956	arg1	stability					958:966	the gas-phase stability	944:966	the gas-phase stability of the DC-SIGN isoforms	944:990	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	0	14	theme	Mass	109:112	arg1	Spectrometry					114:125	Ion Mobility Mass Spectrometry	96:125	Ion Mobility Mass Spectrometry	96:125	Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry.
33462887	6	15	dep	mass	1022:1025	arg1	the					1018:1020	the	1018:1020	the	1018:1020	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	6	16	gly	glycosylation	1133:1145	arg2	sites					1147:1151	glycosylation sites	1133:1151	glycosylation sites	1133:1151	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	4	17	dep	recognition	682:692	arg1	the					665:667	the	665:667	the	665:667	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	0	18	theme	Mobility	100:107	arg1	Spectrometry					114:125	Ion Mobility Mass Spectrometry	96:125	Ion Mobility Mass Spectrometry	96:125	Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry.
33462887	5	19	theme	cross	926:930	arg1	section					932:938	the overall collision cross section	904:938	the overall collision cross section	904:938	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	4	20	theme	extracellular	698:710	arg1	domains					712:718	extracellular domains	698:718	extracellular domains	698:718	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	20	theme	extracellular	698:710	arg1	protein					727:733	the protein	723:733	the protein using sequential exoglycosidase sequencing	723:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	21	from	structures	651:660	arg1	recognition					682:692	carbohydrate recognition	669:692	carbohydrate recognition	669:692	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	21	from	structures	651:660	arg1	domains					712:718	extracellular domains	698:718	extracellular domains	698:718	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	21	from	structures	651:660	arg1	protein					727:733	the protein	723:733	the protein using sequential exoglycosidase sequencing	723:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	1	22	theme	glycosylated	180:191	arg1	proteins					193:200	glycosylated proteins	180:200	glycosylated proteins	180:200	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	5	23	theme	mobility	789:796	arg1	spectrometry					803:814	ion mobility mass spectrometry	785:814	ion mobility mass spectrometry	785:814	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	3	24	theme	O-glycans	568:576	arg1	effects					557:563	the effects	553:563	the effects of O-glycans on the stability of DC-SIGN	553:604	Herein, we report the development and application of a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN.
33462887	5	25	theme	overall	908:914	arg1	section					932:938	the overall collision cross section	904:938	the overall collision cross section	904:938	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	0	26	theme	DC-SIGN	26:32	arg1	Glycoforms					12:21	Glycoforms	12:21	Glycoforms of DC-SIGN	12:32	Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry.
33462887	5	27	theme	single	856:861	arg1	substitutions					878:890	single monosaccharide substitutions	856:890	single monosaccharide substitutions	856:890	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	6	28	theme	modifications	1053:1065	arg1	length					1030:1035	length	1030:1035	length	1030:1035	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	6	28	theme	modifications	1053:1065	arg1	mass					1022:1025	mass	1022:1025	mass	1022:1025	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	5	29	theme	DC-SIGN	975:981	arg1	isoforms					983:990	the DC-SIGN isoforms	971:990	the DC-SIGN isoforms	971:990	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	4	30	theme	Core 1	629:634	arg1	structures					651:660	the Core 1 and 2 O-glycan structures	625:660	the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing	625:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	0	31	theme	Spectrometry	114:125	arg1	Combination					57:67	a Combination	55:67	a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry	55:125	Correlating Glycoforms of DC-SIGN with Stability Using a Combination of Enzymatic Digestion and Ion Mobility Mass Spectrometry.
33462887	2	32	theme	different	304:312	arg1	viruses					314:320	different viruses	304:320	different viruses	304:320	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	5	33	theme	specific	829:836	arg1	O-glycans					838:846	specific O-glycans	829:846	specific O-glycans	829:846	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	5	34	theme	mass	798:801	arg1	spectrometry					803:814	ion mobility mass spectrometry	785:814	ion mobility mass spectrometry	785:814	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	6	35	gly	glycoprotein	1040:1051	arg1	glycoprotein					1040:1051	glycoprotein modifications	1040:1065	glycoprotein modifications	1040:1065	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	4	36	theme	2	640:640	arg1	structures					651:660	the Core 1 and 2 O-glycan structures	625:660	the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing	625:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	1	37	theme	putative	212:219	arg1	role					221:224	a putative role	210:224	a putative role	210:224	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	2	38	gly	glycosylation	354:366	arg1	DC-SIGN					400:406	DC-SIGN	400:406	DC-SIGN	400:406	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	3	39	theme	DC-SIGN	598:604	arg1	stability					585:593	the stability	581:593	the stability of DC-SIGN	581:604	Herein, we report the development and application of a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN.
33462887	5	40	theme	monosaccharide	863:876	arg1	substitutions					878:890	single monosaccharide substitutions	856:890	single monosaccharide substitutions	856:890	Using ion mobility mass spectrometry, we show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the DC-SIGN isoforms.
33462887	2	41	theme	DC-SIGN	400:406	arg1	stability					387:395	stability	387:395	stability	387:395	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	2	41	theme	DC-SIGN	400:406	arg1	folding					375:381	folding	375:381	folding	375:381	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	6	42	theme	glycoprotein	1040:1051	arg1	modifications					1053:1065	glycoprotein modifications	1040:1065	glycoprotein modifications	1040:1065	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	6	43	theme	sites	1147:1151	arg1	number					1123:1128	the number	1119:1128	the number of glycosylation sites	1119:1151	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	6	44	theme	glycosylation	1133:1145	arg1	sites					1147:1151	glycosylation sites	1133:1151	glycosylation sites	1133:1151	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	3	45	from	effects	557:563	arg1	stability					585:593	the stability	581:593	the stability of DC-SIGN	581:604	Herein, we report the development and application of a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN.
33462887	2	46	theme	recognition	269:279	arg1	events					281:286	these recognition events	263:286	these recognition events	263:286	How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported.
33462887	4	47	theme	carbohydrate	669:680	arg1	recognition					682:692	carbohydrate recognition	669:692	carbohydrate recognition	669:692	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	48	theme	protein	727:733	arg1	recognition					682:692	carbohydrate recognition	669:692	carbohydrate recognition	669:692	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	48	theme	protein	727:733	arg1	domains					712:718	extracellular domains	698:718	extracellular domains	698:718	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	4	48	theme	protein	727:733	arg1	protein					727:733	the protein	723:733	the protein using sequential exoglycosidase sequencing	723:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	1	49	theme	immune	132:137	arg1	DC-SIGN					157:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	1	50	contain	has	206:208	arg2	role					221:224	a putative role	210:224	a putative role	210:224	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	1	50	contain	has	206:208	arg1	DC-SIGN					157:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	1	51	theme	scavenger	139:147	arg1	DC-SIGN					157:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	4	52	theme	O-glycan	642:649	arg1	structures					651:660	the Core 1 and 2 O-glycan structures	625:660	the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing	625:776	We first quantify the Core 1 and 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein using sequential exoglycosidase sequencing.
33462887	1	53	theme	viral	242:246	arg1	infection					248:256	viral infection	242:256	viral infection	242:256	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
33462887	6	54	theme	DC-SIGN	1085:1091	arg1	stability					1072:1080	the stability	1068:1080	the stability of DC-SIGN	1068:1091	We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites.
33462887	3	55	dep	development	454:464	arg1	the					450:452	the	450:452	the	450:452	Herein, we report the development and application of a mass-spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN.
33462887	1	56	theme	protein	149:155	arg1	DC-SIGN					157:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN	128:163	The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection.
34279906	2	0	theme	composition	531:541	arg1	measure					505:511	an overall measure	494:511	an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein	494:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	6	1	theme	new	1363:1365	arg1	routes					1367:1372	new routes	1363:1372	new routes	1363:1372	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	2	2	with	potential	455:463	arg1	data					470:473	data	470:473	data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein	470:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	5	3	theme	terminal	959:966	arg1	fucosylation					968:979	terminal fucosylation	959:979	terminal fucosylation	959:979	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	2	4	theme	monosaccharide	516:529	arg1	composition					531:541	monosaccharide composition	516:541	monosaccharide composition	516:541	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	5	5	theme	sample	1130:1135	arg1	preparation					1137:1147	minimal sample preparation	1122:1147	minimal sample preparation	1122:1147	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	2	6	from	advances	354:361	arg1	instrumentation					382:396	high-resolution instrumentation	366:396	high-resolution instrumentation	366:396	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	1	7	theme	resolving	177:185	arg1	structures					187:196	inherently heterogeneous and therefore resolving structures	138:196	inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology	138:262	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	1	7	theme	resolving	177:185	arg1	Glycoproteins					120:132	Glycoproteins	120:132	Glycoproteins	120:132	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	5	8	gly	glycoproteins	1103:1115	arg1	glycoproteins					1103:1115	intact glycoproteins	1096:1115	intact glycoproteins with minimal sample preparation	1096:1147	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	6	9	from	need	1319:1322	arg1	biology					1338:1344	structural biology	1327:1344	structural biology	1327:1344	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	6	10	theme	protein	1271:1277	arg1	glycosylation					1279:1291	protein glycosylation	1271:1291	protein glycosylation	1271:1291	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	2	11	gly	glycosylation	566:578	arg2	sites					580:584	glycosylation sites	566:584	glycosylation sites for a given protein	566:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	5	12	theme	O-glycan	1012:1019	arg1	occupancy					1021:1029	N- and O-glycan occupancy	1005:1029	N- and O-glycan occupancy (i.e., total number of glycans)	1005:1061	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	2	13	theme	glycosylation	566:578	arg1	sites					580:584	glycosylation sites	566:584	glycosylation sites for a given protein	566:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	6	14	theme	native	1166:1171	arg1	NES-MS					1218:1223	NES-MS	1218:1223	NES-MS	1218:1223	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	6	14	theme	native	1166:1171	arg1	spectrometry					1204:1215	native exoglycosidase sequencing mass spectrometry	1166:1215	native exoglycosidase sequencing mass spectrometry (NES-MS)	1166:1224	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	6	15	theme	mass	1199:1202	arg1	NES-MS					1218:1223	NES-MS	1218:1223	NES-MS	1218:1223	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	6	15	theme	mass	1199:1202	arg1	spectrometry					1204:1215	native exoglycosidase sequencing mass spectrometry	1166:1215	native exoglycosidase sequencing mass spectrometry (NES-MS)	1166:1224	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	4	16	theme	structural	907:916	arg1	details					918:924	remarkable glycoprotein structural details	883:924	remarkable glycoprotein structural details	883:924	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	4	17	theme	exoglycosidase	822:835	arg1	sequencing					837:846	glycan exoglycosidase sequencing	815:846	glycan exoglycosidase sequencing	815:846	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	5	18	with	glycoproteins	1103:1115	arg1	preparation					1137:1147	minimal sample preparation	1122:1147	minimal sample preparation	1122:1147	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	0	19	theme	Intact	98:103	arg1	Glycoproteins					105:117	Intact Glycoproteins	98:117	Intact Glycoproteins	98:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	4	20	theme	glycoprotein	894:905	arg1	details					918:924	remarkable glycoprotein structural details	883:924	remarkable glycoprotein structural details	883:924	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	2	21	theme	limited	483:489	arg1	data					470:473	data	470:473	data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein	470:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	2	22	theme	few	425:427	arg1	studies					429:435	comparatively a few studies	409:435	comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein	409:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	0	23	theme	Mass	7:10	arg1	Spectrometry					12:23	Native Mass Spectrometry	0:23	Native Mass Spectrometry	0:23	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	2	24	gly	glycoproteins	327:339	arg1	glycoproteins					327:339	glycoproteins	327:339	glycoproteins	327:339	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	0	25	theme	Native	0:5	arg1	Spectrometry					12:23	Native Mass Spectrometry	0:23	Native Mass Spectrometry	0:23	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	5	26	theme	N-	1005:1006	arg1	occupancy					1021:1029	N- and O-glycan occupancy	1005:1029	N- and O-glycan occupancy (i.e., total number of glycans)	1005:1061	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	3	27	theme	glycan	700:705	arg1	branching					707:715	glycan branching	700:715	glycan branching	700:715	Clearly, these readouts lack glycan topology information, namely, monosaccharide linkage and glycan branching.
34279906	4	28	theme	mass	792:795	arg1	spectrometry					797:808	native mass spectrometry	785:808	native mass spectrometry	785:808	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	6	29	theme	significant	1307:1317	arg1	need					1319:1322	a significant need	1305:1322	a significant need in structural biology that will enable new routes to understand glycoprotein function	1305:1408	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	4	30	gly	glycoprotein	894:905	arg1	glycoprotein					894:905	remarkable glycoprotein structural details	883:924	remarkable glycoprotein structural details	883:924	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	2	31	theme	given	592:596	arg1	protein					598:604	a given protein	590:604	a given protein	590:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	4	32	theme	native	785:790	arg1	spectrometry					797:808	native mass spectrometry	785:808	native mass spectrometry	785:808	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	6	33	theme	sequencing	1188:1197	arg1	NES-MS					1218:1223	NES-MS	1218:1223	NES-MS	1218:1223	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	6	33	theme	sequencing	1188:1197	arg1	spectrometry					1204:1215	native exoglycosidase sequencing mass spectrometry	1166:1215	native exoglycosidase sequencing mass spectrometry (NES-MS)	1166:1224	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	0	34	from	Occupancy	74:82	arg1	Glycoproteins					105:117	Intact Glycoproteins	98:117	Intact Glycoproteins	98:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	3	35	theme	glycan	636:641	arg1	information					652:662	glycan topology information	636:662	glycan topology information	636:662	Clearly, these readouts lack glycan topology information, namely, monosaccharide linkage and glycan branching.
34279906	5	36	theme	N-glycan	939:946	arg1	branching					948:956	N-glycan branching	939:956	N-glycan branching	939:956	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	1	37	theme	major	226:230	arg1	challenge					232:240	a major challenge	224:240	a major challenge in structural biology	224:262	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	6	38	theme	structural	1327:1336	arg1	biology					1338:1344	structural biology	1327:1344	structural biology	1327:1344	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	3	39	theme	monosaccharide	673:686	arg1	linkage					688:694	monosaccharide linkage	673:694	monosaccharide linkage	673:694	Clearly, these readouts lack glycan topology information, namely, monosaccharide linkage and glycan branching.
34279906	1	40	dep	entirety	207:214	arg1	remains					216:222	remains	216:222	remains a major challenge in structural biology	216:262	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	5	41	dep	number	1044:1049	arg1	i.e.					1032:1035	i.e.	1032:1035	i.e.	1032:1035	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	0	42	theme	Structural	52:61	arg1	Detail					63:68	Resolving Structural Detail	42:68	Resolving Structural Detail	42:68	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	42	theme	Structural	52:61	arg1	Glycomics					31:39	Glycomics	31:39	Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins	31:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	6	43	theme	glycoprotein	1388:1399	arg1	function					1401:1408	glycoprotein function	1388:1408	glycoprotein function	1388:1408	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	0	44	from	Detail	63:68	arg1	Glycoproteins					105:117	Intact Glycoproteins	98:117	Intact Glycoproteins	98:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	4	45	theme	remarkable	883:892	arg1	details					918:924	remarkable glycoprotein structural details	883:924	remarkable glycoprotein structural details	883:924	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	1	46	from	challenge	232:240	arg1	biology					256:262	structural biology	245:262	structural biology	245:262	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	2	47	theme	high-resolution	366:380	arg1	instrumentation					382:396	high-resolution instrumentation	366:396	high-resolution instrumentation	366:396	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	0	48	theme	Resolving	42:50	arg1	Detail					63:68	Resolving Structural Detail	42:68	Resolving Structural Detail	42:68	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	48	theme	Resolving	42:50	arg1	Glycomics					31:39	Glycomics	31:39	Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins	31:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	49	from	Glycoproteins	105:117	arg1	Occupancy					74:82	Occupancy	74:82	Occupancy of Glycans on Intact Glycoproteins	74:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	49	from	Glycoproteins	105:117	arg1	Detail					63:68	Resolving Structural Detail	42:68	Resolving Structural Detail	42:68	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	49	from	Glycoproteins	105:117	arg1	Glycomics					31:39	Glycomics	31:39	Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins	31:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	50	dep	Glycomics	31:39	arg1	Occupancy					74:82	Occupancy	74:82	Occupancy of Glycans on Intact Glycoproteins	74:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	50	dep	Glycomics	31:39	arg1	Detail					63:68	Resolving Structural Detail	42:68	Resolving Structural Detail	42:68	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	50	dep	Glycomics	31:39	arg1	Glycomics					31:39	Glycomics	31:39	Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins	31:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	5	51	theme	LacNAc	982:987	arg1	extensions					989:998	LacNAc extensions	982:998	LacNAc extensions	982:998	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	5	52	theme	glycans	1054:1060	arg1	number					1044:1049	total number	1038:1049	total number of glycans	1038:1060	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	5	53	gly	fucosylation	968:979	arg1	glycoproteins					1103:1115	intact glycoproteins	1096:1115	intact glycoproteins with minimal sample preparation	1096:1147	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	5	54	theme	total	1038:1042	arg1	number					1044:1049	total number	1038:1049	total number of glycans	1038:1060	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	3	55	theme	topology	643:650	arg1	information					652:662	glycan topology information	636:662	glycan topology information	636:662	Clearly, these readouts lack glycan topology information, namely, monosaccharide linkage and glycan branching.
34279906	6	56	theme	exoglycosidase	1173:1186	arg1	NES-MS					1218:1223	NES-MS	1218:1223	NES-MS	1218:1223	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	6	56	theme	exoglycosidase	1173:1186	arg1	spectrometry					1204:1215	native exoglycosidase sequencing mass spectrometry	1166:1215	native exoglycosidase sequencing mass spectrometry (NES-MS)	1166:1224	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	4	57	theme	glycan	815:820	arg1	sequencing					837:846	glycan exoglycosidase sequencing	815:846	glycan exoglycosidase sequencing	815:846	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	5	58	theme	intact	1096:1101	arg1	glycoproteins					1103:1115	intact glycoproteins	1096:1115	intact glycoproteins with minimal sample preparation	1096:1147	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	4	59	theme	sequencing	837:846	arg1	combination					853:863	the combination	849:863	the combination	849:863	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	5	60	theme	minimal	1122:1128	arg1	preparation					1137:1147	minimal sample preparation	1122:1147	minimal sample preparation	1122:1147	We show how N-glycan branching, terminal fucosylation, LacNAc extensions, and N- and O-glycan occupancy (i.e., total number of glycans) can be directly characterized on intact glycoproteins with minimal sample preparation.
34279906	4	61	theme	new	761:763	arg1	approach					765:772	a new approach	759:772	a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details	759:924	To address this deficiency, we developed a new approach that joins native mass spectrometry with glycan exoglycosidase sequencing, the combination of which provides remarkable glycoprotein structural details.
34279906	1	62	theme	structural	245:254	arg1	biology					256:262	structural biology	245:262	structural biology	245:262	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	0	63	from	Glycans	87:93	arg1	Glycoproteins					105:117	Intact Glycoproteins	98:117	Intact Glycoproteins	98:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	2	64	theme	mass	272:275	arg1	spectrometry					277:288	Native mass spectrometry	265:288	Native mass spectrometry	265:288	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	1	65	theme	heterogeneous	149:161	arg1	structures					187:196	inherently heterogeneous and therefore resolving structures	138:196	inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology	138:262	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	1	65	theme	heterogeneous	149:161	arg1	Glycoproteins					120:132	Glycoproteins	120:132	Glycoproteins	120:132	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	6	66	gly	glycoprotein	1388:1399	arg1	glycoprotein					1388:1399	glycoprotein function	1388:1408	glycoprotein function	1388:1408	Taken together, native exoglycosidase sequencing mass spectrometry (NES-MS) notably improves our ability to characterize protein glycosylation, addressing a significant need in structural biology that will enable new routes to understand glycoprotein function.
34279906	2	67	theme	overall	497:503	arg1	measure					505:511	an overall measure	494:511	an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein	494:604	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	2	68	theme	Native	265:270	arg1	spectrometry					277:288	Native mass spectrometry	265:288	Native mass spectrometry	265:288	Native mass spectrometry has transformed our ability to study glycoproteins, and despite advances in high-resolution instrumentation, there are comparatively a few studies demonstrating its potential with data largely limited to an overall measure of monosaccharide composition for all glycans across glycosylation sites for a given protein.
34279906	1	69	from	structures	187:196	arg1	entirety					207:214	their entirety remains a major challenge in structural biology	201:262	their entirety remains a major challenge in structural biology	201:262	Glycoproteins are inherently heterogeneous and therefore resolving structures in their entirety remains a major challenge in structural biology.
34279906	0	70	theme	Glycans	87:93	arg1	Occupancy					74:82	Occupancy	74:82	Occupancy of Glycans on Intact Glycoproteins	74:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	70	theme	Glycans	87:93	arg1	Detail					63:68	Resolving Structural Detail	42:68	Resolving Structural Detail	42:68	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34279906	0	70	theme	Glycans	87:93	arg1	Glycomics					31:39	Glycomics	31:39	Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins	31:117	Native Mass Spectrometry Meets Glycomics: Resolving Structural Detail and Occupancy of Glycans on Intact Glycoproteins.
34257876	12	0	theme	line	1852:1855	arg1	network					1827:1833	the GPX network	1819:1833	the GPX network of the PNT2 cell line	1819:1855	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	11	1	theme	cell	1739:1742	arg1	surface					1744:1750	the PNT2 cell surface	1730:1750	the PNT2 cell surface	1730:1750	Glycoprotein-protein interactions involving unique glycoforms on the PNT2 cell surface were identified using the optimized and validated method.
34257876	8	2	theme	polypeptide	1308:1318	arg1	backbones					1320:1328	polypeptide backbones	1308:1328	polypeptide backbones	1308:1328	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	7	3	from	interactions	917:928	arg1	membrane					942:949	the cell membrane	933:949	the cell membrane using liquid chromatography-mass spectrometry (LC-MS)	933:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	6	4	theme	interactions	762:773	arg1	elucidation					732:742	Mechanistic elucidation	720:742	Mechanistic elucidation of glycan-protein interactions	720:773	Mechanistic elucidation of glycan-protein interactions has thus far remained elusive.
34257876	9	5	theme	peptide-glycan-peptide	1343:1364	arg1	pairs					1366:1370	The coupled peptide-glycan-peptide pairs	1331:1370	The coupled peptide-glycan-peptide pairs after cross-linking	1331:1390	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	14	6	from	roles	2127:2131	arg1	complexes					2155:2163	protein complexes	2147:2163	protein complexes	2147:2163	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	7	7	theme	spectrometry	851:862	arg1	workflow					872:879	a cross-linking mass spectrometry (XL-MS) workflow	830:879	a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS)	830:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	8	8	theme	cultures	1139:1146	arg1	treatment					1121:1129	treatment	1121:1129	treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones	1121:1328	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	2	9	theme	cell	326:329	arg1	membranes					331:339	cell membranes	326:339	cell membranes	326:339	The method provides information on previously unknown extensive glycomic interactions on cell membranes.
34257876	12	10	theme	structures	1923:1932	arg1	roles					1897:1901	the biological roles	1882:1901	the biological roles of different glycan structures within protein complexes	1882:1957	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	10	11	theme	protein	1593:1599	arg1	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	11	theme	protein	1593:1599	arg1	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	11	theme	protein	1593:1599	arg1	glycosylation					1552:1564	glycosylation	1552:1564	glycosylation	1552:1564	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	11	theme	protein	1593:1599	arg1	glycoform					1571:1579	the glycoform	1567:1579	the glycoform	1567:1579	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	11	theme	protein	1593:1599	arg1	site					1544:1547	the site	1540:1547	the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair	1540:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	5	12	theme	significant	558:568	arg1	advances					570:577	significant advances	558:577	significant advances	558:577	Although significant advances have been made to identify protein-protein interactions in living cells, only modest advances have been made on glycan-protein interactions.
34257876	12	13	theme	protein	1941:1947	arg1	complexes					1949:1957	protein complexes	1941:1957	protein complexes	1941:1957	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	8	14	theme	cell	1134:1137	arg1	cultures					1139:1146	cell cultures	1134:1146	cell cultures	1134:1146	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	7	15	theme	liquid	957:962	arg1	spectrometry					984:995	liquid chromatography-mass spectrometry	957:995	liquid chromatography-mass spectrometry (LC-MS)	957:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	7	15	theme	liquid	957:962	arg1	LC-MS					998:1002	LC-MS	998:1002	LC-MS	998:1002	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	4	16	theme	cellular	532:539	arg1	events					541:546	many cellular events	527:546	many cellular events	527:546	Glycan-protein interactions are fundamental elements in many cellular events.
34257876	9	17	theme	latest	1418:1423	arg1	techniques					1425:1434	the latest techniques	1414:1434	the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software	1414:1502	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	5	18	theme	modest	657:662	arg1	advances					664:671	only modest advances	652:671	only modest advances	652:671	Although significant advances have been made to identify protein-protein interactions in living cells, only modest advances have been made on glycan-protein interactions.
34257876	3	19	theme	vast	346:349	arg1	majority					351:358	The vast majority	342:358	The vast majority of membrane proteins	342:379	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	4	20	theme	fundamental	503:513	arg1	interactions					486:497	Glycan-protein interactions	471:497	Glycan-protein interactions	471:497	Glycan-protein interactions are fundamental elements in many cellular events.
34257876	4	20	theme	fundamental	503:513	arg1	elements					515:522	fundamental elements	503:522	fundamental elements in many cellular events	503:546	Glycan-protein interactions are fundamental elements in many cellular events.
34257876	12	21	theme	glycan	1916:1921	arg1	structures					1923:1932	different glycan structures	1906:1932	different glycan structures	1906:1932	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	10	22	gly	glycosylation	1552:1564	arg2	glycoform					1571:1579	the glycoform	1567:1579	the glycoform	1567:1579	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	22	gly	glycosylation	1552:1564	arg2	site					1544:1547	the site	1540:1547	the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair	1540:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	22	gly	glycosylation	1552:1564	arg2	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	22	gly	glycosylation	1552:1564	arg2	glycosylation					1552:1564	glycosylation	1552:1564	glycosylation	1552:1564	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	22	gly	glycosylation	1552:1564	arg1	pair					1645:1648	the cross-linked pair	1628:1648	the cross-linked pair	1628:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	22	gly	glycosylation	1552:1564	arg2	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	2	23	theme	extensive	291:299	arg1	interactions					310:321	previously unknown extensive glycomic interactions	272:321	previously unknown extensive glycomic interactions	272:321	The method provides information on previously unknown extensive glycomic interactions on cell membranes.
34257876	5	24	theme	living	638:643	arg1	cells					645:649	living cells	638:649	living cells	638:649	Although significant advances have been made to identify protein-protein interactions in living cells, only modest advances have been made on glycan-protein interactions.
34257876	3	25	theme	proteins	372:379	arg1	majority					351:358	The vast majority	342:358	The vast majority of membrane proteins	342:379	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	6	26	theme	glycan-protein	747:760	arg1	interactions					762:773	glycan-protein interactions	747:773	glycan-protein interactions	747:773	Mechanistic elucidation of glycan-protein interactions has thus far remained elusive.
34257876	0	27	theme	cell	96:99	arg1	surfaces					101:108	cell surfaces	96:108	cell surfaces	96:108	Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces.
34257876	9	28	theme	bioinformatics	1480:1493	arg1	software					1495:1502	bioinformatics software	1480:1502	bioinformatics software	1480:1502	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	5	29	theme	glycan-protein	691:704	arg1	interactions					706:717	glycan-protein interactions	691:717	glycan-protein interactions	691:717	Although significant advances have been made to identify protein-protein interactions in living cells, only modest advances have been made on glycan-protein interactions.
34257876	1	30	theme	membrane	197:204	arg1	proteins					206:213	membrane proteins	197:213	membrane proteins through sialic acids	197:234	A cross-linking method is developed to elucidate glycan-mediated interactions between membrane proteins through sialic acids.
34257876	12	31	theme	biological	1886:1895	arg1	roles					1897:1901	the biological roles	1882:1901	the biological roles of different glycan structures within protein complexes	1882:1957	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	10	32	theme	target	1610:1615	arg1	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	33	theme	glycoform	1571:1579	arg1	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	33	theme	glycoform	1571:1579	arg1	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	33	theme	glycoform	1571:1579	arg1	glycosylation					1552:1564	glycosylation	1552:1564	glycosylation	1552:1564	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	33	theme	glycoform	1571:1579	arg1	glycoform					1571:1579	the glycoform	1567:1579	the glycoform	1567:1579	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	33	theme	glycoform	1571:1579	arg1	site					1544:1547	the site	1540:1547	the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair	1540:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	11	34	theme	unique	1709:1714	arg1	glycoforms					1716:1725	unique glycoforms	1709:1725	unique glycoforms	1709:1725	Glycoprotein-protein interactions involving unique glycoforms on the PNT2 cell surface were identified using the optimized and validated method.
34257876	12	35	theme	cell	1847:1850	arg1	line					1852:1855	the PNT2 cell line	1838:1855	the PNT2 cell line	1838:1855	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	3	36	theme	complicated	403:413	arg1	structures					422:431	complicated glycan structures	403:431	complicated glycan structures attached to the polypeptide backbone	403:468	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	8	37	with	glycans	1277:1283	arg1	amines					1298:1303	primary amines	1290:1303	primary amines	1290:1303	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	8	38	theme	-cyclooctyne	1202:1213	arg1	reagent					1167:1173	a synthesized reagent	1153:1173	a synthesized reagent	1153:1173	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	8	39	theme	azido	1041:1045	arg1	groups					1047:1052	incorporating azido groups	1027:1052	incorporating azido groups on cell surface glycans	1027:1076	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	3	40	theme	polypeptide	449:459	arg1	backbone					461:468	the polypeptide backbone	445:468	the polypeptide backbone	445:468	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	10	41	theme	cross-linked	1632:1643	arg1	pair					1645:1648	the cross-linked pair	1628:1648	the cross-linked pair	1628:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	0	42	theme	Glycan-protein	0:13	arg1	spectrometry					34:45	Glycan-protein cross-linking mass spectrometry	0:45	Glycan-protein cross-linking mass spectrometry	0:45	Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces.
34257876	13	43	theme	unexplored	2046:2055	arg1	interactions					2057:2068	previously unexplored interactions	2035:2068	previously unexplored interactions	2035:2068	Furthermore, we were able to build glycoprotein-protein complex models for previously unexplored interactions.
34257876	0	44	theme	mass	29:32	arg1	spectrometry					34:45	Glycan-protein cross-linking mass spectrometry	0:45	Glycan-protein cross-linking mass spectrometry	0:45	Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces.
34257876	8	45	theme	surface	1062:1068	arg1	glycans					1070:1076	cell surface glycans	1057:1076	cell surface glycans	1057:1076	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	8	46	with	treatment	1121:1129	arg1	reagent					1167:1173	a synthesized reagent	1153:1173	a synthesized reagent	1153:1173	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	12	47	theme	PNT2	1842:1845	arg1	line					1852:1855	the PNT2 cell line	1838:1855	the PNT2 cell line	1838:1855	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	0	48	theme	acid-mediated	62:74	arg1	networks					84:91	sialic acid-mediated protein networks	55:91	sialic acid-mediated protein networks	55:91	Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces.
34257876	8	49	theme	sialic	1255:1260	arg1	azides					1267:1272	the sialic acid azides	1251:1272	the sialic acid azides	1251:1272	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	3	50	gly	glycosylated	385:396	arg1	majority					351:358	The vast majority	342:358	The vast majority of membrane proteins	342:379	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	8	51	theme	azides	1267:1272	arg1	cross-linking					1234:1246	the cross-linking	1230:1246	the cross-linking of the sialic acid azides on glycans with primary amines	1230:1303	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	13	52	theme	glycoprotein-protein	1995:2014	arg1	models					2024:2029	glycoprotein-protein complex models	1995:2029	glycoprotein-protein complex models for previously unexplored interactions	1995:2068	Furthermore, we were able to build glycoprotein-protein complex models for previously unexplored interactions.
34257876	10	53	theme	glycosylation	1552:1564	arg1	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	53	theme	glycosylation	1552:1564	arg1	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	53	theme	glycosylation	1552:1564	arg1	glycosylation					1552:1564	glycosylation	1552:1564	glycosylation	1552:1564	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	53	theme	glycosylation	1552:1564	arg1	glycoform					1571:1579	the glycoform	1567:1579	the glycoform	1567:1579	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	53	theme	glycosylation	1552:1564	arg1	site					1544:1547	the site	1540:1547	the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair	1540:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	8	54	theme	primary	1290:1296	arg1	amines					1298:1303	primary amines	1290:1303	primary amines	1290:1303	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	4	55	theme	Glycan-protein	471:484	arg1	interactions					486:497	Glycan-protein interactions	471:497	Glycan-protein interactions	471:497	Glycan-protein interactions are fundamental elements in many cellular events.
34257876	4	55	theme	Glycan-protein	471:484	arg1	elements					515:522	fundamental elements	503:522	fundamental elements in many cellular events	503:546	Glycan-protein interactions are fundamental elements in many cellular events.
34257876	9	56	theme	coupled	1335:1341	arg1	pairs					1366:1370	The coupled peptide-glycan-peptide pairs	1331:1370	The coupled peptide-glycan-peptide pairs after cross-linking	1331:1390	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	7	57	theme	mass	846:849	arg1	XL-MS					865:869	XL-MS	865:869	XL-MS	865:869	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	7	57	theme	mass	846:849	arg1	spectrometry					851:862	mass spectrometry	846:862	a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS)	830:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	9	58	from	techniques	1425:1434	arg1	analyses					1467:1474	glycoproteomic and glycomic analyses	1439:1474	glycoproteomic and glycomic analyses	1439:1474	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	9	58	from	techniques	1425:1434	arg1	software					1495:1502	bioinformatics software	1480:1502	bioinformatics software	1480:1502	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	11	59	dep	optimized	1778:1786	arg1	the					1774:1776	the	1774:1776	the	1774:1776	Glycoprotein-protein interactions involving unique glycoforms on the PNT2 cell surface were identified using the optimized and validated method.
34257876	11	60	theme	PNT2	1734:1737	arg1	surface					1744:1750	the PNT2 cell surface	1730:1750	the PNT2 cell surface	1730:1750	Glycoprotein-protein interactions involving unique glycoforms on the PNT2 cell surface were identified using the optimized and validated method.
34257876	5	61	from	interactions	622:633	arg1	cells					645:649	living cells	638:649	living cells	638:649	Although significant advances have been made to identify protein-protein interactions in living cells, only modest advances have been made on glycan-protein interactions.
34257876	14	62	theme	glycans	2136:2142	arg1	roles					2127:2131	the roles	2123:2131	the roles of glycans in protein complexes	2123:2163	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	8	63	theme	synthesized	1155:1165	arg1	reagent					1167:1173	a synthesized reagent	1153:1173	a synthesized reagent	1153:1173	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	6	64	theme	Mechanistic	720:730	arg1	elucidation					732:742	Mechanistic elucidation	720:742	Mechanistic elucidation of glycan-protein interactions	720:773	Mechanistic elucidation of glycan-protein interactions has thus far remained elusive.
34257876	5	65	theme	protein-protein	606:620	arg1	interactions					622:633	protein-protein interactions	606:633	protein-protein interactions in living cells	606:649	Although significant advances have been made to identify protein-protein interactions in living cells, only modest advances have been made on glycan-protein interactions.
34257876	1	66	theme	sialic	223:228	arg1	acids					230:234	sialic acids	223:234	sialic acids	223:234	A cross-linking method is developed to elucidate glycan-mediated interactions between membrane proteins through sialic acids.
34257876	10	67	theme	source	1586:1591	arg1	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	7	68	theme	cross-linking	832:844	arg1	workflow					872:879	a cross-linking mass spectrometry (XL-MS) workflow	830:879	a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS)	830:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	2	69	theme	unknown	283:289	arg1	interactions					310:321	previously unknown extensive glycomic interactions	272:321	previously unknown extensive glycomic interactions	272:321	The method provides information on previously unknown extensive glycomic interactions on cell membranes.
34257876	7	70	theme	chromatography-mass	964:982	arg1	spectrometry					984:995	liquid chromatography-mass spectrometry	957:995	liquid chromatography-mass spectrometry (LC-MS)	957:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	7	70	theme	chromatography-mass	964:982	arg1	LC-MS					998:1002	LC-MS	998:1002	LC-MS	998:1002	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	14	71	theme	future	2099:2104	arg1	understanding					2106:2118	our future understanding	2095:2118	our future understanding of the roles of glycans in protein complexes	2095:2163	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	3	72	theme	membrane	363:370	arg1	proteins					372:379	membrane proteins	363:379	membrane proteins	363:379	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	11	73	theme	Glycoprotein-protein	1665:1684	arg1	interactions					1686:1697	Glycoprotein-protein interactions	1665:1697	Glycoprotein-protein interactions involving unique glycoforms on the PNT2 cell surface	1665:1750	Glycoprotein-protein interactions involving unique glycoforms on the PNT2 cell surface were identified using the optimized and validated method.
34257876	4	74	from	elements	515:522	arg1	events					541:546	many cellular events	527:546	many cellular events	527:546	Glycan-protein interactions are fundamental elements in many cellular events.
34257876	9	75	theme	glycoproteomic	1439:1452	arg1	analyses					1467:1474	glycoproteomic and glycomic analyses	1439:1474	glycoproteomic and glycomic analyses	1439:1474	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	4	76	theme	many	527:530	arg1	events					541:546	many cellular events	527:546	many cellular events	527:546	Glycan-protein interactions are fundamental elements in many cellular events.
34257876	9	77	theme	glycomic	1458:1465	arg1	analyses					1467:1474	glycoproteomic and glycomic analyses	1439:1474	glycoproteomic and glycomic analyses	1439:1474	The coupled peptide-glycan-peptide pairs after cross-linking were identified using the latest techniques in glycoproteomic and glycomic analyses and bioinformatics software.
34257876	2	78	theme	glycomic	301:308	arg1	interactions					310:321	previously unknown extensive glycomic interactions	272:321	previously unknown extensive glycomic interactions	272:321	The method provides information on previously unknown extensive glycomic interactions on cell membranes.
34257876	1	79	theme	glycan-mediated	160:174	arg1	interactions					176:187	glycan-mediated interactions	160:187	glycan-mediated interactions between membrane proteins through sialic acids	160:234	A cross-linking method is developed to elucidate glycan-mediated interactions between membrane proteins through sialic acids.
34257876	12	80	theme	different	1906:1914	arg1	structures					1923:1932	different glycan structures	1906:1932	different glycan structures	1906:1932	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	8	81	from	cross-linking	1234:1246	arg1	glycans					1277:1283	glycans	1277:1283	glycans with primary amines	1277:1303	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	3	82	attach	attached	433:440	arg2	structures					422:431	complicated glycan structures	403:431	complicated glycan structures attached to the polypeptide backbone	403:468	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	3	82	attach	attached	433:440	arg1	backbone					461:468	the polypeptide backbone	445:468	the polypeptide backbone	445:468	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	8	83	from	groups	1047:1052	arg1	glycans					1070:1076	cell surface glycans	1057:1076	cell surface glycans	1057:1076	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	10	84	link	cross-linked	1632:1643	arg1	pair					1645:1648	the cross-linked pair	1628:1648	the cross-linked pair	1628:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	14	85	from	complexes	2155:2163	arg1	understanding					2106:2118	our future understanding	2095:2118	our future understanding of the roles of glycans in protein complexes	2095:2163	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	10	86	theme	protein	1617:1623	arg1	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	86	theme	protein	1617:1623	arg1	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	86	theme	protein	1617:1623	arg1	glycosylation					1552:1564	glycosylation	1552:1564	glycosylation	1552:1564	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	86	theme	protein	1617:1623	arg1	glycoform					1571:1579	the glycoform	1567:1579	the glycoform	1567:1579	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	86	theme	protein	1617:1623	arg1	site					1544:1547	the site	1540:1547	the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair	1540:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	14	87	theme	roles	2127:2131	arg1	understanding					2106:2118	our future understanding	2095:2118	our future understanding of the roles of glycans in protein complexes	2095:2163	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	2	88	from	information	257:267	arg1	interactions					310:321	previously unknown extensive glycomic interactions	272:321	previously unknown extensive glycomic interactions	272:321	The method provides information on previously unknown extensive glycomic interactions on cell membranes.
34257876	2	88	from	information	257:267	arg1	membranes					331:339	cell membranes	326:339	cell membranes	326:339	The method provides information on previously unknown extensive glycomic interactions on cell membranes.
34257876	10	89	from	information	1525:1535	arg1	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	89	from	information	1525:1535	arg1	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	89	from	information	1525:1535	arg1	glycosylation					1552:1564	glycosylation	1552:1564	glycosylation	1552:1564	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	89	from	information	1525:1535	arg1	glycoform					1571:1579	the glycoform	1567:1579	the glycoform	1567:1579	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	89	from	information	1525:1535	arg1	site					1544:1547	the site	1540:1547	the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair	1540:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	3	90	theme	glycan	415:420	arg1	structures					422:431	complicated glycan structures	403:431	complicated glycan structures attached to the polypeptide backbone	403:468	The vast majority of membrane proteins are glycosylated with complicated glycan structures attached to the polypeptide backbone.
34257876	10	91	theme	pair	1645:1648	arg1	protein					1617:1623	the target protein	1606:1623	the target protein	1606:1623	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	91	theme	pair	1645:1648	arg1	protein					1593:1599	the source protein	1582:1599	the source protein	1582:1599	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	91	theme	pair	1645:1648	arg1	glycosylation					1552:1564	glycosylation	1552:1564	glycosylation	1552:1564	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	10	91	theme	pair	1645:1648	arg1	glycoform					1571:1579	the glycoform	1567:1579	the glycoform	1567:1579	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	0	92	theme	cross-linking	15:27	arg1	spectrometry					34:45	Glycan-protein cross-linking mass spectrometry	0:45	Glycan-protein cross-linking mass spectrometry	0:45	Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces.
34257876	8	93	theme	incorporating	1027:1039	arg1	groups					1047:1052	incorporating azido groups	1027:1052	incorporating azido groups on cell surface glycans	1027:1076	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	1	94	theme	cross-linking	113:125	arg1	method					127:132	A cross-linking method	111:132	A cross-linking method	111:132	A cross-linking method is developed to elucidate glycan-mediated interactions between membrane proteins through sialic acids.
34257876	12	95	theme	GPX	1823:1825	arg1	network					1827:1833	the GPX network	1819:1833	the GPX network of the PNT2 cell line	1819:1855	We built the GPX network of the PNT2 cell line and further investigated the biological roles of different glycan structures within protein complexes.
34257876	14	96	from	understanding	2106:2118	arg1	complexes					2155:2163	protein complexes	2147:2163	protein complexes	2147:2163	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	0	97	theme	sialic	55:60	arg1	networks					84:91	sialic acid-mediated protein networks	55:91	sialic acid-mediated protein networks	55:91	Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces.
34257876	7	98	theme	cell	937:940	arg1	membrane					942:949	the cell membrane	933:949	the cell membrane using liquid chromatography-mass spectrometry (LC-MS)	933:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	8	99	theme	cell	1057:1060	arg1	glycans					1070:1076	cell surface glycans	1057:1076	cell surface glycans	1057:1076	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	11	100	theme	validated	1792:1800	arg1	method					1802:1807	validated method	1792:1807	validated method	1792:1807	Glycoprotein-protein interactions involving unique glycoforms on the PNT2 cell surface were identified using the optimized and validated method.
34257876	0	101	theme	protein	76:82	arg1	networks					84:91	sialic acid-mediated protein networks	55:91	sialic acid-mediated protein networks	55:91	Glycan-protein cross-linking mass spectrometry reveals sialic acid-mediated protein networks on cell surfaces.
34257876	8	102	theme	acid	1262:1265	arg1	azides					1267:1272	the sialic acid azides	1251:1272	the sialic acid azides	1251:1272	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	14	103	theme	cell	2172:2175	arg1	surface					2177:2183	the cell surface	2168:2183	the cell surface	2168:2183	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	10	104	gly	glycoform	1571:1579	arg1	pair					1645:1648	the cross-linked pair	1628:1648	the cross-linked pair	1628:1648	With this approach, information on the site of glycosylation, the glycoform, the source protein, and the target protein of the cross-linked pair were obtained.
34257876	7	105	theme	glycan-protein	902:915	arg1	interactions					917:928	glycan-protein interactions	902:928	glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS)	902:1003	Therefore, we developed a cross-linking mass spectrometry (XL-MS) workflow to directly identify glycan-protein interactions on the cell membrane using liquid chromatography-mass spectrometry (LC-MS).
34257876	8	106	theme	biosynthetic	1086:1097	arg1	pathways					1099:1106	biosynthetic pathways	1086:1106	biosynthetic pathways	1086:1106	This method involved incorporating azido groups on cell surface glycans through biosynthetic pathways, followed by treatment of cell cultures with a synthesized reagent, N-hydroxysuccinimide (NHS)-cyclooctyne, which allowed the cross-linking of the sialic acid azides on glycans with primary amines on polypeptide backbones.
34257876	14	107	theme	protein	2147:2153	arg1	complexes					2155:2163	protein complexes	2147:2163	protein complexes	2147:2163	The method will advance our future understanding of the roles of glycans in protein complexes on the cell surface.
34257876	13	108	theme	complex	2016:2022	arg1	models					2024:2029	glycoprotein-protein complex models	1995:2029	glycoprotein-protein complex models for previously unexplored interactions	1995:2068	Furthermore, we were able to build glycoprotein-protein complex models for previously unexplored interactions.
32710848	0	0	theme	Human	88:92	arg1	Model					111:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	2	1	from	interrogation	451:463	arg1	formation					513:521	tissue formation	506:521	tissue formation	506:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	3	2	theme	CRISPR-Cas9	532:542	arg1	targeting					549:557	CRISPR-Cas9 gene targeting	532:557	CRISPR-Cas9 gene targeting	532:557	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	0	3	theme	CRISPR-Cas9-Engineered	65:86	arg1	Model					111:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	0	4	from	Functions	10:18	arg1	Epithelia					40:48	Human Epithelia	34:48	Human Epithelia	34:48	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	6	5	theme	tissue	1161:1166	arg1	models					1168:1173	other organotypic tissue models	1143:1173	other organotypic tissue models	1143:1173	The strategy is also applicable to other organotypic tissue models.
32710848	3	6	theme	gene	544:547	arg1	targeting					549:557	CRISPR-Cas9 gene targeting	532:557	CRISPR-Cas9 gene targeting	532:557	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	1	7	theme	tissue	274:279	arg1	formation					281:289	tissue formation	274:289	tissue formation	274:289	The glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete.
32710848	0	8	theme	Skin	106:109	arg1	Model					111:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	3	9	theme	O-linked	711:718	arg1	glycoproteins					720:732	glycoproteins	720:732	glycoproteins	720:732	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	4	10	theme	tested	858:863	arg1	glycoconjugates					865:879	all tested glycoconjugates	854:879	all tested glycoconjugates	854:879	This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates.
32710848	4	11	theme	skin	800:803	arg1	formation					805:813	skin formation	800:813	skin formation	800:813	This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates.
32710848	4	12	theme	distinct	780:787	arg1	changes					789:795	distinct changes	780:795	distinct changes in skin formation associated with a loss of features for all tested glycoconjugates	780:879	This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates.
32710848	0	13	theme	Organotypic	94:104	arg1	Model					111:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	a CRISPR-Cas9-Engineered Human Organotypic Skin Model	63:115	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	4	14	theme	tissue	756:761	arg1	library					763:769	This tissue library	751:769	This tissue library	751:769	This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates.
32710848	6	15	theme	organotypic	1149:1159	arg1	models					1168:1173	other organotypic tissue models	1143:1173	other organotypic tissue models	1143:1173	The strategy is also applicable to other organotypic tissue models.
32710848	5	16	theme	further	1016:1022	arg1	dissection					1032:1041	further genetic dissection	1016:1041	further genetic dissection	1016:1041	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	5	17	theme	glycoconjugates	964:978	arg1	functions					951:959	the distinct functions	938:959	the distinct functions of glycoconjugates	938:978	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	2	18	theme	capacities	425:434	arg1	dissection					388:397	genetic dissection	380:397	genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation	380:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	5	19	theme	distinct	942:949	arg1	functions					951:959	the distinct functions	938:959	the distinct functions of glycoconjugates	938:978	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	0	20	theme	Human	34:38	arg1	Epithelia					40:48	Human Epithelia	34:48	Human Epithelia	34:48	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	4	21	from	changes	789:795	arg1	formation					805:813	skin formation	800:813	skin formation	800:813	This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates.
32710848	5	22	theme	genetic	1024:1030	arg1	dissection					1032:1041	further genetic dissection	1016:1041	further genetic dissection	1016:1041	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	6	23	theme	other	1143:1147	arg1	models					1168:1173	other organotypic tissue models	1143:1173	other organotypic tissue models	1143:1173	The strategy is also applicable to other organotypic tissue models.
32710848	2	24	theme	glycosylation	411:423	arg1	capacities					425:434	cellular glycosylation capacities	402:434	cellular glycosylation capacities	402:434	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	25	theme	distinct	481:488	arg1	types					497:501	distinct glycan types	481:501	distinct glycan types	481:501	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	3	26	theme	skin	599:602	arg1	tissues					604:610	3D organotypic skin tissues	584:610	3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids	584:748	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	2	27	theme	cellular	402:409	arg1	capacities					425:434	cellular glycosylation capacities	402:434	cellular glycosylation capacities	402:434	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	0	28	theme	Essential	0:8	arg1	Functions					10:18	Essential Functions	0:18	Essential Functions of Glycans in Human Epithelia	0:48	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	3	29	theme	tissues	604:610	arg1	library					573:579	a library	571:579	a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids	571:748	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	5	30	theme	phenotypic	918:927	arg1	cues					929:932	phenotypic cues	918:932	phenotypic cues for the distinct functions of glycoconjugates	918:978	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	0	31	theme	Glycans	23:29	arg1	Functions					10:18	Essential Functions	0:18	Essential Functions of Glycans in Human Epithelia	0:48	Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
32710848	3	32	theme	3D	584:585	arg1	tissues					604:610	3D organotypic skin tissues	584:610	3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids	584:748	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	3	33	link	O-linked	711:718	arg1	glycoproteins					720:732	glycoproteins	720:732	glycoproteins	720:732	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	3	34	theme	organotypic	587:597	arg1	tissues					604:610	3D organotypic skin tissues	584:610	3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids	584:748	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	5	35	theme	structural	1078:1087	arg1	features					1089:1096	the specific structural features	1065:1096	the specific structural features involved	1065:1105	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	2	36	theme	interrogation	451:463	arg1	dissection					388:397	genetic dissection	380:397	genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation	380:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	37	theme	tissue	506:511	arg1	formation					513:521	tissue formation	506:521	tissue formation	506:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	38	from	formation	513:521	arg1	capacities					425:434	cellular glycosylation capacities	402:434	cellular glycosylation capacities	402:434	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	38	from	formation	513:521	arg1	interrogation					451:463	systematic interrogation	440:463	systematic interrogation	440:463	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	39	theme	systematic	440:449	arg1	interrogation					451:463	systematic interrogation	440:463	systematic interrogation	440:463	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	5	40	theme	skin	898:901	arg1	model					903:907	The organotypic skin model	882:907	The organotypic skin model	882:907	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	5	40	theme	skin	898:901	arg1	resource					1003:1010	a unique resource	994:1010	a unique resource for further genetic dissection and identification of the specific structural features involved	994:1105	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	3	41	theme	glycan	665:670	arg1	structures					672:681	glycan structures	665:681	glycan structures	665:681	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	2	42	theme	roles	472:476	arg1	capacities					425:434	cellular glycosylation capacities	402:434	cellular glycosylation capacities	402:434	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	42	theme	roles	472:476	arg1	interrogation					451:463	systematic interrogation	440:463	systematic interrogation	440:463	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	1	43	theme	importance	231:240	arg1	understanding					210:222	our understanding	206:222	our understanding of the importance of select glycan structures for tissue formation and homeostasis	206:305	The glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete.
32710848	2	44	theme	types	497:501	arg1	roles					472:476	the roles	468:476	the roles of distinct glycan types in tissue formation	468:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	3	45	gly	glycoproteins	720:732	arg1	glycoproteins					720:732	glycoproteins	720:732	glycoproteins	720:732	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	3	46	used	used	527:530	arg2	We					524:525	We	524:525	We	524:525	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	2	47	theme	glycan	490:495	arg1	types					497:501	distinct glycan types	481:501	distinct glycan types	481:501	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	3	48	theme	glycoproteins	720:732	arg1	types					695:699	the main types	686:699	the main types of N- and O-linked glycoproteins and glycolipids	686:748	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	5	49	theme	features	1089:1096	arg1	identification					1047:1060	identification	1047:1060	identification	1047:1060	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	5	49	theme	features	1089:1096	arg1	dissection					1032:1041	further genetic dissection	1016:1041	further genetic dissection	1016:1041	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	2	50	from	capacities	425:434	arg1	formation					513:521	tissue formation	506:521	tissue formation	506:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	51	theme	organotypic	347:357	arg1	platform					359:366	a human organotypic platform	339:366	a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation	339:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	5	52	theme	specific	1069:1076	arg1	features					1089:1096	the specific structural features	1065:1096	the specific structural features involved	1065:1105	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	3	53	theme	N-	704:705	arg1	types					695:699	the main types	686:699	the main types of N- and O-linked glycoproteins and glycolipids	686:748	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	4	54	theme	features	841:848	arg1	loss					833:836	a loss	831:836	a loss of features for all tested glycoconjugates	831:879	This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates.
32710848	2	55	theme	human	341:345	arg1	platform					359:366	a human organotypic platform	339:366	a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation	339:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	3	56	theme	main	690:693	arg1	types					695:699	the main types	686:699	the main types of N- and O-linked glycoproteins and glycolipids	686:748	We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids.
32710848	1	57	theme	characteristic	140:153	arg1	changes					155:161	characteristic changes	140:161	characteristic changes	140:161	The glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete.
32710848	1	58	theme	select	245:250	arg1	structures					259:268	select glycan structures	245:268	select glycan structures	245:268	The glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete.
32710848	5	59	theme	organotypic	886:896	arg1	model					903:907	The organotypic skin model	882:907	The organotypic skin model	882:907	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	5	59	theme	organotypic	886:896	arg1	resource					1003:1010	a unique resource	994:1010	a unique resource for further genetic dissection and identification of the specific structural features involved	994:1105	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	5	60	theme	unique	996:1001	arg1	model					903:907	The organotypic skin model	882:907	The organotypic skin model	882:907	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	5	60	theme	unique	996:1001	arg1	resource					1003:1010	a unique resource	994:1010	a unique resource for further genetic dissection and identification of the specific structural features involved	994:1105	The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved.
32710848	1	61	theme	glycan	252:257	arg1	structures					259:268	select glycan structures	245:268	select glycan structures	245:268	The glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete.
32710848	2	62	from	roles	472:476	arg1	formation					513:521	tissue formation	506:521	tissue formation	506:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	2	63	theme	genetic	380:386	arg1	dissection					388:397	genetic dissection	380:397	genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation	380:521	Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation.
32710848	1	64	theme	structures	259:268	arg1	importance					231:240	the importance	227:240	the importance of select glycan structures for tissue formation and homeostasis	227:305	The glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete.
33797266	3	0	theme	SPhosAuNTf2	473:483	arg1	counterion					444:453	The counterion	440:453	The counterion	440:453	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	3	0	theme	SPhosAuNTf2	473:483	arg1	ligand					463:468	the ligand	459:468	the ligand	459:468	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	4	1	theme	oligosaccharides	702:717	arg1	synthesis					653:661	the stereocontrolled synthesis	632:661	the stereocontrolled synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei	632:779	This approach was effectively applied to the stereocontrolled synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei.
33797266	3	2	theme	dramatic	506:513	arg1	effect					515:520	a dramatic effect	504:520	a dramatic effect	504:520	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	2	3	theme	SphosAuNTf2-promoted	245:264	arg1	glycosidation					266:278	SphosAuNTf2-promoted glycosidation	245:278	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols	245:351	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent β-selectivities.
33797266	3	4	theme	1,2-cis-β-linked	546:561	arg1	6-deoxy-d-manno-heptosides					563:588	the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides	542:588	the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides	542:588	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	4	5	theme	6-deoxy-β-d-manno-heptopyranose	670:700	arg1	oligosaccharides					702:717	the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	666:717	the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei	666:779	This approach was effectively applied to the stereocontrolled synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei.
33797266	3	6	theme	6-deoxy-d-manno-heptosides	563:588	arg1	formation					529:537	the formation	525:537	the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides	525:588	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	1	7	theme	promoter-assisted	113:129	arg1	approach					145:152	a promoter-assisted glycosidation approach	111:152	a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	111:242	We report a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides.
33797266	0	8	theme	Stereoselective	18:32	arg1	Synthesis					34:42	Promoter-Assisted Stereoselective Synthesis	0:42	Promoter-Assisted Stereoselective Synthesis of the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides	0:98	Promoter-Assisted Stereoselective Synthesis of the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides.
33797266	1	9	theme	glycosidation	131:143	arg1	approach					145:152	a promoter-assisted glycosidation approach	111:152	a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	111:242	We report a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides.
33797266	0	10	theme	Promoter-Assisted	0:16	arg1	Synthesis					34:42	Promoter-Assisted Stereoselective Synthesis	0:42	Promoter-Assisted Stereoselective Synthesis of the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides	0:98	Promoter-Assisted Stereoselective Synthesis of the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides.
33797266	2	11	theme	o-hexynylbenzoate	314:330	arg1	glycosidation					266:278	SphosAuNTf2-promoted glycosidation	245:278	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols	245:351	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent β-selectivities.
33797266	0	12	theme	6-Deoxy-β-d-manno-heptopyranose	51:81	arg1	Oligosaccharides					83:98	the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides	47:98	the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides	47:98	Promoter-Assisted Stereoselective Synthesis of the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides.
33797266	2	13	theme	6-deoxy-d-manno-heptopyranosyl	283:312	arg1	o-hexynylbenzoate					314:330	6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate	283:330	6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate	283:330	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent β-selectivities.
33797266	2	14	theme	6-deoxy-d-manno-heptosides	373:398	arg1	range					364:368	a range	362:368	a range of 6-deoxy-d-manno-heptosides	362:398	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent β-selectivities.
33797266	4	15	theme	stereocontrolled	636:651	arg1	synthesis					653:661	the stereocontrolled synthesis	632:661	the stereocontrolled synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei	632:779	This approach was effectively applied to the stereocontrolled synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei.
33797266	3	16	link	1,2-cis-β-linked	546:561	arg1	6-deoxy-d-manno-heptosides					563:588	the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides	542:588	the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides	542:588	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	3	17	contain	have	499:502	arg2	effect					515:520	a dramatic effect	504:520	a dramatic effect	504:520	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	3	17	contain	have	499:502	arg1	counterion					444:453	The counterion	440:453	The counterion	440:453	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	3	17	contain	have	499:502	arg1	ligand					463:468	the ligand	459:468	the ligand	459:468	The counterion and the ligand of SPhosAuNTf2 were found to have a dramatic effect on the formation of the 1,2-cis-β-linked 6-deoxy-d-manno-heptosides.
33797266	1	18	theme	stereoselective	162:176	arg1	synthesis					178:186	the stereoselective synthesis	158:186	the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	158:242	We report a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides.
33797266	0	19	theme	Oligosaccharides	83:98	arg1	Synthesis					34:42	Promoter-Assisted Stereoselective Synthesis	0:42	Promoter-Assisted Stereoselective Synthesis of the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides	0:98	Promoter-Assisted Stereoselective Synthesis of the 6-Deoxy-β-d-manno-heptopyranose Oligosaccharides.
33797266	2	20	with	glycosidation	266:278	arg1	alcohols					344:351	common alcohols	337:351	common alcohols	337:351	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent β-selectivities.
33797266	2	21	theme	excellent	413:421	arg1	β-selectivities					423:437	excellent β-selectivities	413:437	excellent β-selectivities	413:437	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent β-selectivities.
33797266	2	22	theme	common	337:342	arg1	alcohols					344:351	common alcohols	337:351	common alcohols	337:351	SphosAuNTf2-promoted glycosidation of 6-deoxy-d-manno-heptopyranosyl o-hexynylbenzoate with common alcohols afforded a range of 6-deoxy-d-manno-heptosides with good to excellent β-selectivities.
33797266	1	23	theme	6-deoxy-β-d-manno-heptopyranose	195:225	arg1	oligosaccharides					227:242	the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	191:242	the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	191:242	We report a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides.
33797266	4	24	theme	relevant	719:726	arg1	oligosaccharides					702:717	the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	666:717	the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei	666:779	This approach was effectively applied to the stereocontrolled synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides relevant to Burkholderia pseudomallei and Burkholderia mallei.
33797266	1	25	theme	oligosaccharides	227:242	arg1	synthesis					178:186	the stereoselective synthesis	158:186	the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides	158:242	We report a promoter-assisted glycosidation approach for the stereoselective synthesis of the 6-deoxy-β-d-manno-heptopyranose oligosaccharides.
33026663	9	0	theme	enzyme	1412:1417	arg1	stability					1419:1427	enzyme stability	1412:1427	enzyme stability	1412:1427	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	9	1	theme	analysis	1287:1294	arg1	importance					1273:1282	the importance	1269:1282	the importance of analysis of glycan structures attached to glycoproteins	1269:1341	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	1	2	theme	alkyl	167:171	arg1	surfactants					217:227	important and effective surfactants	193:227	important and effective surfactants	193:227	Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants.
33026663	1	2	theme	alkyl	167:171	arg1	glycosides					173:182	alkyl glycosides	167:182	alkyl glycosides that are important and effective surfactants	167:227	Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants.
33026663	9	3	theme	enzymatic	1537:1545	arg1	synthesis					1547:1555	industrial enzymatic synthesis	1526:1555	industrial enzymatic synthesis	1526:1555	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	0	4	theme	N-glycoforms	81:92	arg1	selection					58:66	chromatographic selection	42:66	chromatographic selection of different N-glycoforms of yeast invertase	42:111	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	5	5	gly	glycoforms	567:576	arg1	invertase					557:565	invertase glycoforms	557:576	invertase glycoforms (EINV)	557:583	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	8	6	theme	lowest	1180:1185	arg1	amount					1187:1192	the lowest amount	1176:1192	the lowest amount of phosphorylated N-glycans	1176:1220	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	8	6	theme	lowest	1180:1185	arg1	N-glycans					1212:1220	phosphorylated N-glycans	1197:1220	phosphorylated N-glycans	1197:1220	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	8	7	theme	synthesis	1098:1106	arg1	yield					1086:1090	yield	1086:1090	yield	1086:1090	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	8	7	theme	synthesis	1098:1106	arg1	efficiency					1071:1080	efficiency	1071:1080	efficiency	1071:1080	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	1	8	theme	glycosides	173:182	arg1	synthesis					154:162	synthesis	154:162	synthesis of alkyl glycosides that are important and effective surfactants	154:227	Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants.
33026663	9	9	theme	synthesis	1547:1555	arg1	yield					1517:1521	yield	1517:1521	yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports	1517:1621	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	0	10	theme	invertase	103:111	arg1	N-glycoforms					81:92	different N-glycoforms	71:92	different N-glycoforms of yeast invertase	71:111	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	8	11	theme	stabile	1150:1156	arg1	glycoform					1158:1166	the most stabile glycoform	1141:1166	the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans	1141:1220	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	7	12	used	used	991:994	arg2	differences					927:937	Observed differences	918:937	Observed differences in stability of different invertase glycoforms	918:984	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	0	13	theme	yeast	97:101	arg1	invertase					103:111	yeast invertase	97:111	yeast invertase	97:111	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	4	14	theme	N-glycosylation	451:465	arg1	pathways					467:474	yeast N-glycosylation pathways	445:474	yeast N-glycosylation pathways	445:474	However, yeast N-glycosylation pathways may synthesize plethora of N-glycan structures.
33026663	2	15	theme	solvent	307:313	arg1	content					288:294	increased content	278:294	increased content of organic solvent	278:313	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	7	16	theme	glycoforms	975:984	arg1	stability					942:950	stability	942:950	stability of different invertase glycoforms	942:984	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	2	17	from	Stability	230:238	arg1	environment					261:271	the environment	257:271	the environment with increased content of organic solvent	257:313	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	7	18	theme	different	955:963	arg1	glycoforms					975:984	different invertase glycoforms	955:984	different invertase glycoforms	955:984	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	4	19	theme	yeast	445:449	arg1	pathways					467:474	yeast N-glycosylation pathways	445:474	yeast N-glycosylation pathways	445:474	However, yeast N-glycosylation pathways may synthesize plethora of N-glycan structures.
33026663	0	20	gly	N-glycoforms	81:92	arg1	invertase					103:111	yeast invertase	97:111	yeast invertase	97:111	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	6	21	theme	water-alcohol	814:826	arg1	solutions					828:836	water-alcohol solutions	814:836	water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans	814:915	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	9	22	theme	chromatographic	1560:1574	arg1	selection					1576:1584	chromatographic selection	1560:1584	chromatographic selection of glycoforms on monolithic supports	1560:1621	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	7	23	gly	glycoforms	975:984	arg1	invertase					965:973	different invertase glycoforms	955:984	different invertase glycoforms	955:984	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	9	24	from	stability	1419:1427	arg1	regard					1432:1437	regard	1432:1437	regard to particular reaction environment	1432:1472	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	9	25	theme	yield	1517:1521	arg1	improvement					1502:1512	improvement	1502:1512	improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports	1502:1621	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	5	26	theme	invertase	557:565	arg1	EINV					579:582	EINV	579:582	EINV	579:582	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	5	26	theme	invertase	557:565	arg1	glycoforms					567:576	invertase glycoforms	557:576	invertase glycoforms (EINV)	557:583	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	9	27	theme	reaction	1453:1460	arg1	environment					1462:1472	particular reaction environment	1442:1472	particular reaction environment	1442:1472	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	5	28	theme	different	722:730	arg1	EINV1-EINV3					744:754	EINV1-EINV3	744:754	EINV1-EINV3	744:754	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	5	28	theme	different	722:730	arg1	glycoforms					732:741	different glycoforms	722:741	different glycoforms (EINV1-EINV3)	722:755	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	5	29	theme	glycoforms	567:576	arg1	mixture					546:552	A total natural crude mixture	524:552	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae	524:623	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	1	30	theme	important	193:201	arg1	surfactants					217:227	important and effective surfactants	193:227	important and effective surfactants	193:227	Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants.
33026663	1	30	theme	important	193:201	arg1	glycosides					173:182	alkyl glycosides	167:182	alkyl glycosides that are important and effective surfactants	167:227	Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants.
33026663	7	31	theme	Observed	918:925	arg1	differences					927:937	Observed differences	918:937	Observed differences in stability of different invertase glycoforms	918:984	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	7	32	from	differences	927:937	arg1	stability					942:950	stability	942:950	stability of different invertase glycoforms	942:984	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	5	33	theme	anion-exchange	648:661	arg1	chromatography					663:676	anion-exchange chromatography	648:676	anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3)	648:755	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	9	34	dep	monolithic	1603:1612	arg1	supports					1614:1621	supports	1614:1621	supports	1614:1621	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	6	35	theme	different	789:797	arg1	stabilities					799:809	different stabilities	789:809	different stabilities	789:809	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	0	36	theme	enzymatic	19:27	arg1	synthesis					29:37	enzymatic synthesis	19:37	enzymatic synthesis	19:37	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	6	37	theme	phosphate	888:896	arg1	phosphate					888:896	phosphate	888:896	phosphate	888:896	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	6	37	theme	phosphate	888:896	arg1	amount					878:883	the amount	874:883	the amount of phosphate bound to N-glycans	874:915	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	7	38	theme	synthesis	1056:1064	arg1	productivity					1007:1018	productivity	1007:1018	productivity of methyl β-d-fructofuranoside (MF) synthesis	1007:1064	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	9	39	theme	glycan	1299:1304	arg1	structures					1306:1315	glycan structures	1299:1315	glycan structures attached to glycoproteins	1299:1341	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	5	40	theme	total	526:530	arg1	mixture					546:552	A total natural crude mixture	524:552	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae	524:623	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	1	41	theme	effective	207:215	arg1	surfactants					217:227	important and effective surfactants	193:227	important and effective surfactants	193:227	Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants.
33026663	1	41	theme	effective	207:215	arg1	glycosides					173:182	alkyl glycosides	167:182	alkyl glycosides that are important and effective surfactants	167:227	Invertases are glycosidases applied for synthesis of alkyl glycosides that are important and effective surfactants.
33026663	2	42	theme	organic	299:305	arg1	solvent					307:313	organic solvent	299:313	organic solvent	299:313	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	4	43	theme	N-glycan	503:510	arg1	structures					512:521	N-glycan structures	503:521	N-glycan structures	503:521	However, yeast N-glycosylation pathways may synthesize plethora of N-glycan structures.
33026663	6	44	theme	Separated	758:766	arg1	glycoforms					768:777	Separated glycoforms	758:777	Separated glycoforms	758:777	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	5	45	theme	natural	532:538	arg1	mixture					546:552	A total natural crude mixture	524:552	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae	524:623	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	9	46	gly	glycoproteins	1329:1341	arg1	glycoproteins					1329:1341	glycoproteins	1329:1341	glycoproteins	1329:1341	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	5	47	from	chromatography	663:676	arg1	monolithic					692:701	monolithic	692:701	monolithic	692:701	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	8	48	theme	N-glycans	1212:1220	arg1	amount					1187:1192	the lowest amount	1176:1192	the lowest amount of phosphorylated N-glycans	1176:1220	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	8	48	theme	N-glycans	1212:1220	arg1	N-glycans					1212:1220	phosphorylated N-glycans	1197:1220	phosphorylated N-glycans	1197:1220	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	5	49	theme	crude	540:544	arg1	mixture					546:552	A total natural crude mixture	524:552	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae	524:623	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	9	50	dep	charge	1401:1406	arg1	the					1389:1391	the	1389:1391	the	1389:1391	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	0	51	theme	synthesis	29:37	arg1	yield					10:14	yield	10:14	yield of enzymatic synthesis	10:37	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	8	52	used	utilized	1238:1245	arg2	glycoform					1158:1166	the most stabile glycoform	1141:1166	the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans	1141:1220	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	9	53	from	impact	1366:1371	arg1	stability					1419:1427	enzyme stability	1412:1427	enzyme stability	1412:1427	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	9	53	from	impact	1366:1371	arg1	charge					1401:1406	surface charge	1393:1406	surface charge	1393:1406	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	8	54	dep	efficiency	1071:1080	arg1	The					1067:1069	The	1067:1069	The	1067:1069	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	2	55	with	environment	261:271	arg1	content					288:294	increased content	278:294	increased content of organic solvent	278:313	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	9	56	theme	structures	1306:1315	arg1	analysis					1287:1294	analysis	1287:1294	analysis of glycan structures attached to glycoproteins	1287:1341	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	4	57	theme	structures	512:521	arg1	plethora					491:498	plethora	491:498	plethora of N-glycan structures	491:521	However, yeast N-glycosylation pathways may synthesize plethora of N-glycan structures.
33026663	2	58	theme	invertases	243:252	arg1	Stability					230:238	Stability	230:238	Stability of invertases in the environment with increased content of organic solvent	230:313	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	9	59	theme	particular	1442:1451	arg1	environment					1462:1472	particular reaction environment	1442:1472	particular reaction environment	1442:1472	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	0	60	theme	chromatographic	42:56	arg1	selection					58:66	chromatographic selection	42:66	chromatographic selection of different N-glycoforms of yeast invertase	42:111	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	9	61	theme	N-glycans	1376:1384	arg1	impact					1366:1371	different impact	1356:1371	different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment	1356:1472	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	2	62	theme	glycosidases	358:369	arg1	productivity					342:353	productivity	342:353	productivity of glycosidases	342:369	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	5	63	dep	monolithic	692:701	arg1	supports					703:710	supports	703:710	supports to obtain different glycoforms (EINV1-EINV3)	703:755	A total natural crude mixture of invertase glycoforms (EINV) extracted from Saccharomyces cerevisiae was subfractionated by anion-exchange chromatography on industrial monolithic supports to obtain different glycoforms (EINV1-EINV3).
33026663	8	64	theme	MF	1095:1096	arg1	synthesis					1098:1106	MF synthesis	1095:1106	MF synthesis	1095:1106	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	9	65	theme	surface	1393:1399	arg1	charge					1401:1406	surface charge	1393:1406	surface charge	1393:1406	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	2	66	theme	increased	278:286	arg1	content					288:294	increased content	278:294	increased content of organic solvent	278:313	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	6	67	theme	direct	850:855	arg1	correlation					857:867	direct correlation	850:867	direct correlation with the amount of phosphate bound to N-glycans	850:915	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	2	68	theme	productivity	342:353	arg1	increase					330:337	increase	330:337	increase of productivity of glycosidases	330:369	Stability of invertases in the environment with increased content of organic solvent is crucial for increase of productivity of glycosidases.
33026663	7	69	theme	methyl	1023:1028	arg1	β-d-fructofuranoside					1030:1049	methyl β-d-fructofuranoside	1023:1049	methyl β-d-fructofuranoside (MF) synthesis	1023:1064	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	7	69	theme	methyl	1023:1028	arg1	MF					1052:1053	MF	1052:1053	MF	1052:1053	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	7	70	theme	invertase	965:973	arg1	glycoforms					975:984	different invertase glycoforms	955:984	different invertase glycoforms	955:984	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	0	71	theme	different	71:79	arg1	N-glycoforms					81:92	different N-glycoforms	71:92	different N-glycoforms of yeast invertase	71:111	Increased yield of enzymatic synthesis by chromatographic selection of different N-glycoforms of yeast invertase.
33026663	9	72	theme	different	1356:1364	arg1	impact					1366:1371	different impact	1356:1371	different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment	1356:1472	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	7	73	theme	β-d-fructofuranoside	1030:1049	arg1	synthesis					1056:1064	methyl β-d-fructofuranoside (MF) synthesis	1023:1064	methyl β-d-fructofuranoside (MF) synthesis	1023:1064	Observed differences in stability of different invertase glycoforms were used to improve productivity of methyl β-d-fructofuranoside (MF) synthesis.
33026663	9	74	attach	attached	1317:1324	arg1	glycoproteins					1329:1341	glycoproteins	1329:1341	glycoproteins	1329:1341	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	9	74	attach	attached	1317:1324	arg2	structures					1306:1315	glycan structures	1299:1315	glycan structures attached to glycoproteins	1299:1341	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	6	75	with	correlation	857:867	arg1	phosphate					888:896	phosphate	888:896	phosphate	888:896	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	6	75	with	correlation	857:867	arg1	amount					878:883	the amount	874:883	the amount of phosphate bound to N-glycans	874:915	Separated glycoforms exhibited different stabilities in water-alcohol solutions that are in direct correlation with the amount of phosphate bound to N-glycans.
33026663	9	76	theme	glycoforms	1589:1598	arg1	selection					1576:1584	chromatographic selection	1560:1584	chromatographic selection of glycoforms on monolithic supports	1560:1621	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	9	77	from	charge	1401:1406	arg1	regard					1432:1437	regard	1432:1437	regard to particular reaction environment	1432:1472	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	9	78	from	selection	1576:1584	arg1	monolithic					1603:1612	monolithic	1603:1612	monolithic	1603:1612	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
33026663	8	79	theme	phosphorylated	1197:1210	arg1	N-glycans					1212:1220	phosphorylated N-glycans	1197:1220	phosphorylated N-glycans	1197:1220	The efficiency and yield of MF synthesis were improved more than 50% when the most stabile glycoform bearing the lowest amount of phosphorylated N-glycans is selected and utilized.
33026663	9	80	theme	industrial	1526:1535	arg1	synthesis					1547:1555	industrial enzymatic synthesis	1526:1555	industrial enzymatic synthesis	1526:1555	These data underline the importance of analysis of glycan structures attached to glycoproteins, demonstrate different impact of N-glycans on the surface charge and enzyme stability in regard to particular reaction environment, and provide a platform for improvement of yield of industrial enzymatic synthesis by chromatographic selection of glycoforms on monolithic supports.
32817316	4	0	theme	antigen-presenting	832:849	arg1	cells					851:855	antigen-presenting cells	832:855	antigen-presenting cells	832:855	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	8	1	theme	C-type	1664:1669	arg1	lectin					1671:1676	C-type lectin	1664:1676	C-type lectin receptor-deficient mice	1664:1700	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	2	2	theme	CIDCA	379:383	arg1	8348					385:388	probiotic Lactobacillus kefiri CIDCA 8348	348:388	probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348)	348:399	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	2	2	theme	CIDCA	379:383	arg1	SLP-8348					391:398	SLP-8348	391:398	SLP-8348	391:398	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	8	3	theme	SLP-8321	1750:1757	arg1	activity					1738:1745	the immunostimulatory activity	1716:1745	the immunostimulatory activity of SLP-8321	1716:1757	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	7	4	theme	LPS-induced	1376:1386	arg1	activation					1388:1397	LPS-induced activation	1376:1397	LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells	1376:1473	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	7	5	theme	dendritic	1459:1467	arg1	cells					1469:1473	murine bone marrow-derived dendritic cells	1432:1473	murine bone marrow-derived dendritic cells	1432:1473	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	9	6	theme	potential	1943:1951	arg1	application					1953:1963	the potential application	1939:1963	the potential application of these SLPs as new adjuvants	1939:1994	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	8	7	theme	receptor-deficient	1678:1695	arg1	mice					1697:1700	C-type lectin receptor-deficient mice	1664:1700	C-type lectin receptor-deficient mice	1664:1700	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	4	8	theme	L.	814:815	arg1	SLPs					824:827	the L. kefiri SLPs	810:827	the L. kefiri SLPs	810:827	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	7	9	theme	bone	1439:1442	arg1	cells					1469:1473	murine bone marrow-derived dendritic cells	1432:1473	murine bone marrow-derived dendritic cells	1432:1473	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	1	10	theme	nanostructured	171:184	arg1	envelope					186:193	a nanostructured envelope	169:193	a nanostructured envelope that covers the surface of different prokaryotes	169:242	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	4	11	theme	SLPs	824:827	arg1	effect					800:805	the immunomodulatory effect	779:805	the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells	779:855	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	4	11	theme	SLPs	824:827	arg1	recognition					736:746	their recognition	730:746	their recognition by C-type lectin receptors	730:773	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	9	12	theme	SLPs	1974:1977	arg1	application					1953:1963	the potential application	1939:1963	the potential application of these SLPs as new adjuvants	1939:1994	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	9	12	theme	SLPs	1974:1977	arg1	mechanisms					2026:2035	the protein glycosylation mechanisms	2000:2035	the protein glycosylation mechanisms in these bacteria	2000:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	2	13	theme	S-layer	322:328	arg1	glycoprotein					330:341	the S-layer glycoprotein	318:341	the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348)	318:399	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	7	14	theme	RAW264.7	1407:1414	arg1	macrophages					1416:1426	RAW264.7 macrophages	1407:1426	RAW264.7 macrophages	1407:1426	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	9	15	theme	new	1982:1984	arg1	adjuvants					1986:1994	new adjuvants	1982:1994	new adjuvants	1982:1994	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	6	16	theme	glycans	1326:1332	arg1	workflow					1296:1303	a glycomic workflow	1285:1303	a glycomic workflow of the permethylated glycans	1285:1332	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	6	16	theme	glycans	1326:1332	arg1	analysis					1272:1279	a site-specific analysis	1256:1279	a site-specific analysis	1256:1279	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	5	17	theme	hexose	1080:1085	arg1	chains					1087:1092	hexose chains	1080:1092	hexose chains	1080:1092	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	0	18	theme	kefiri	35:40	arg1	proteins					50:57	Lactobacillus kefiri S-layer proteins	21:57	Lactobacillus kefiri S-layer proteins	21:57	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	8	19	link	marrow-derived	1628:1641	arg1	cells					1653:1657	bone marrow-derived dendritic cells	1623:1657	bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice	1623:1700	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	9	20	theme	protein	2004:2010	arg1	mechanisms					2026:2035	the protein glycosylation mechanisms	2000:2035	the protein glycosylation mechanisms in these bacteria	2000:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	1	21	theme	glyco	141:145	arg1	SLPs					158:161	SLPs	158:161	SLPs	158:161	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	1	21	theme	glyco	141:145	arg1	-proteins					147:155	S-layer (glyco)-proteins	132:155	S-layer (glyco)-proteins (SLPs)	132:162	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	6	22	located	detected	1141:1148	arg2	signals					1128:1134	No N-glycosylation signals	1109:1134	No N-glycosylation signals	1109:1134	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	6	22	located	detected	1141:1148	arg1	SLP-8321					1166:1173	SLP-8321	1166:1173	SLP-8321	1166:1173	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	6	22	located	detected	1141:1148	arg1	SLP-8348					1153:1160	SLP-8348	1153:1160	SLP-8348	1153:1160	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	9	23	theme	mechanisms	2026:2035	arg1	investigation					1917:1929	further investigation	1909:1929	further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria	1909:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	9	24	from	application	1953:1963	arg1	bacteria					2046:2053	these bacteria	2040:2053	these bacteria	2040:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	0	25	theme	glycosylation	73:85	arg1	patterns					87:94	distinct glycosylation patterns	64:94	distinct glycosylation patterns	64:94	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	5	26	theme	anion-exchange	875:888	arg1	detector					924:931	High-performance anion-exchange chromatography-pulse amperometric detector	858:931	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination	858:961	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	5	27	from	differences	1051:1061	arg1	length					1070:1075	the length	1066:1075	the length of hexose chains	1066:1092	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	5	28	theme	amperometric	911:922	arg1	detector					924:931	High-performance anion-exchange chromatography-pulse amperometric detector	858:931	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination	858:961	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	0	29	theme	lectin	115:120	arg1	partners					122:129	different lectin partners	105:129	different lectin partners	105:129	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	8	30	theme	human	1868:1872	arg1	DC-SIGN					1874:1880	human DC-SIGN	1868:1880	human DC-SIGN	1868:1880	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	2	31	theme	lectin	454:459	arg1	receptor					461:468	macrophage inducible C-type lectin receptor	426:468	macrophage inducible C-type lectin receptor	426:468	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	2	31	theme	lectin	454:459	arg1	Mincle					418:423	Mincle	418:423	Mincle (macrophage inducible C-type lectin receptor)	418:469	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	6	32	contain	carrying	1220:1227	arg2	N-glycans					1237:1245	complex N-glycans	1229:1245	complex N-glycans	1229:1245	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	6	32	contain	carrying	1220:1227	arg1	sites					1214:1218	two sites	1210:1218	two sites carrying complex N-glycans	1210:1245	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	2	33	theme	inducible	437:445	arg1	lectin					454:459	macrophage inducible C-type lectin	426:459	macrophage inducible C-type lectin receptor	426:468	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	0	34	theme	Lactobacillus	21:33	arg1	proteins					50:57	Lactobacillus kefiri S-layer proteins	21:57	Lactobacillus kefiri S-layer proteins	21:57	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	1	35	theme	S-layer	132:138	arg1	SLPs					158:161	SLPs	158:161	SLPs	158:161	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	1	35	theme	S-layer	132:138	arg1	-proteins					147:155	S-layer (glyco)-proteins	132:155	S-layer (glyco)-proteins (SLPs)	132:162	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	9	36	from	mechanisms	2026:2035	arg1	bacteria					2046:2053	these bacteria	2040:2053	these bacteria	2040:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	4	37	theme	immunomodulatory	783:798	arg1	effect					800:805	the immunomodulatory effect	779:805	the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells	779:855	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	0	38	theme	S-layer	42:48	arg1	proteins					50:57	Lactobacillus kefiri S-layer proteins	21:57	Lactobacillus kefiri S-layer proteins	21:57	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	2	39	theme	kefiri	372:377	arg1	8348					385:388	probiotic Lactobacillus kefiri CIDCA 8348	348:388	probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348)	348:399	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	2	39	theme	kefiri	372:377	arg1	SLP-8348					391:398	SLP-8348	391:398	SLP-8348	391:398	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	7	40	theme	similar	1522:1528	arg1	effect					1530:1535	a similar effect	1520:1535	a similar effect	1520:1535	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	4	41	theme	lectin	758:763	arg1	receptors					765:773	C-type lectin receptors	751:773	C-type lectin receptors	751:773	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	0	42	with	Immunostimulation	0:16	arg1	patterns					87:94	distinct glycosylation patterns	64:94	distinct glycosylation patterns	64:94	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	2	43	theme	probiotic	348:356	arg1	8348					385:388	probiotic Lactobacillus kefiri CIDCA 8348	348:388	probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348)	348:399	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	2	43	theme	probiotic	348:356	arg1	SLP-8348					391:398	SLP-8348	391:398	SLP-8348	391:398	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	1	44	theme	different	222:230	arg1	prokaryotes					232:242	different prokaryotes	222:242	different prokaryotes	222:242	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	6	45	theme	N-glycosylation	1112:1126	arg1	signals					1128:1134	No N-glycosylation signals	1109:1134	No N-glycosylation signals	1109:1134	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	9	46	theme	further	1909:1915	arg1	investigation					1917:1929	further investigation	1909:1929	further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria	1909:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	7	47	contain	have	1515:1518	arg1	SLP-8321					1493:1500	SLP-8321	1493:1500	SLP-8321	1493:1500	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	7	47	contain	have	1515:1518	arg2	effect					1530:1535	a similar effect	1520:1535	a similar effect	1520:1535	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	7	47	contain	have	1515:1518	arg1	SLP-5818					1506:1513	SLP-5818	1506:1513	SLP-5818	1506:1513	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	8	48	theme	dendritic	1643:1651	arg1	cells					1653:1657	bone marrow-derived dendritic cells	1623:1657	bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice	1623:1700	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	6	49	theme	glycomic	1287:1294	arg1	workflow					1296:1303	a glycomic workflow	1285:1303	a glycomic workflow of the permethylated glycans	1285:1332	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	8	50	theme	immunostimulatory	1720:1736	arg1	activity					1738:1745	the immunostimulatory activity	1716:1745	the immunostimulatory activity of SLP-8321	1716:1757	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	1	51	theme	immunomodulatory	253:268	arg1	activity					270:277	immunomodulatory activity	253:277	immunomodulatory activity	253:277	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	5	52	from	component	991:999	arg1	O-glycans					1008:1016	the O-glycans	1004:1016	the O-glycans of the three SLPs	1004:1034	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	9	53	theme	application	1953:1963	arg1	investigation					1917:1929	further investigation	1909:1929	further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria	1909:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	8	54	theme	lectin	1671:1676	arg1	mice					1697:1700	C-type lectin receptor-deficient mice	1664:1700	C-type lectin receptor-deficient mice	1664:1700	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	6	55	theme	site-specific	1258:1270	arg1	analysis					1272:1279	a site-specific analysis	1256:1279	a site-specific analysis	1256:1279	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	7	56	from	differences	1555:1565	arg1	patterns					1590:1597	their glycosylation patterns	1570:1597	their glycosylation patterns	1570:1597	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	2	57	from	8348	385:388	arg1	glycoprotein					330:341	the S-layer glycoprotein	318:341	the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348)	318:399	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	7	58	theme	marrow-derived	1444:1457	arg1	cells					1469:1473	murine bone marrow-derived dendritic cells	1432:1473	murine bone marrow-derived dendritic cells	1432:1473	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	4	59	gly	glycosylation	621:633	arg1	SLP-8321					668:675	SLP-8321	668:675	SLP-8321	668:675	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	4	59	gly	glycosylation	621:633	arg1	SLP-5818					682:689	SLP-5818	682:689	SLP-5818	682:689	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	4	59	gly	glycosylation	621:633	arg1	SLP-8348					658:665	SLP-8348	658:665	SLP-8348	658:665	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	4	59	gly	glycosylation	621:633	arg1	SLPs					652:655	three SLPs	646:655	three SLPs	646:655	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	7	60	theme	murine	1432:1437	arg1	cells					1469:1473	murine bone marrow-derived dendritic cells	1432:1473	murine bone marrow-derived dendritic cells	1432:1473	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	4	61	theme	SLPs	652:655	arg1	pattern					635:641	the glycosylation pattern	617:641	the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818,	617:690	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	9	62	from	investigation	1917:1929	arg1	bacteria					2046:2053	these bacteria	2040:2053	these bacteria	2040:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	6	63	theme	complex	1229:1235	arg1	N-glycans					1237:1245	complex N-glycans	1229:1245	complex N-glycans	1229:1245	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	4	64	theme	glycosylation	621:633	arg1	pattern					635:641	the glycosylation pattern	617:641	the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818,	617:690	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	6	65	theme	permethylated	1312:1324	arg1	glycans					1326:1332	the permethylated glycans	1308:1332	the permethylated glycans	1308:1332	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	5	66	theme	chains	1087:1092	arg1	length					1070:1075	the length	1066:1075	the length of hexose chains	1066:1092	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	4	67	from	effect	800:805	arg1	cells					851:855	antigen-presenting cells	832:855	antigen-presenting cells	832:855	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	9	68	theme	glycosylation	2012:2024	arg1	mechanisms					2026:2035	the protein glycosylation mechanisms	2000:2035	the protein glycosylation mechanisms in these bacteria	2000:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	4	69	from	recognition	736:746	arg1	cells					851:855	antigen-presenting cells	832:855	antigen-presenting cells	832:855	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	5	70	theme	High-performance	858:873	arg1	detector					924:931	High-performance anion-exchange chromatography-pulse amperometric detector	858:931	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination	858:961	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	7	71	link	marrow-derived	1444:1457	arg1	cells					1469:1473	murine bone marrow-derived dendritic cells	1432:1473	murine bone marrow-derived dendritic cells	1432:1473	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	0	72	theme	different	105:113	arg1	partners					122:129	different lectin partners	105:129	different lectin partners	105:129	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	5	73	theme	chromatography-pulse	890:909	arg1	detector					924:931	High-performance anion-exchange chromatography-pulse amperometric detector	858:931	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination	858:961	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	7	74	theme	glycosylation	1576:1588	arg1	patterns					1590:1597	their glycosylation patterns	1570:1597	their glycosylation patterns	1570:1597	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	8	75	theme	murine	1849:1854	arg1	ortholog					1856:1863	murine ortholog	1849:1863	murine ortholog of human DC-SIGN	1849:1880	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	5	76	theme	major	985:989	arg1	component					991:999	the major component	981:999	the major component in the O-glycans of the three SLPs	981:1034	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	5	76	theme	major	985:989	arg1	glucose					970:976	glucose	970:976	glucose	970:976	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	2	77	theme	glycans	526:532	arg1	integrity					509:517	the integrity	505:517	the integrity of its glycans	505:532	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	9	78	from	bacteria	2046:2053	arg1	investigation					1917:1929	further investigation	1909:1929	further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria	1909:2053	These findings encourage further investigation of both the potential application of these SLPs as new adjuvants and the protein glycosylation mechanisms in these bacteria.
32817316	8	79	from	mice	1697:1700	arg1	cells					1653:1657	bone marrow-derived dendritic cells	1623:1657	bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice	1623:1700	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	8	80	theme	DC-SIGN	1874:1880	arg1	ortholog					1856:1863	murine ortholog	1849:1863	murine ortholog of human DC-SIGN	1849:1880	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	4	81	dep	L.	814:815	arg1	kefiri					817:822	kefiri	817:822	kefiri	817:822	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	7	82	from	activation	1388:1397	arg1	macrophages					1416:1426	RAW264.7 macrophages	1407:1426	RAW264.7 macrophages	1407:1426	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	7	82	from	activation	1388:1397	arg1	cells					1469:1473	murine bone marrow-derived dendritic cells	1432:1473	murine bone marrow-derived dendritic cells	1432:1473	SLP-8348 was previously shown to enhance LPS-induced activation on both RAW264.7 macrophages and murine bone marrow-derived dendritic cells; we now show that SLP-8321 and SLP-5818 have a similar effect regardless of the differences in their glycosylation patterns.
32817316	2	83	theme	C-type	447:452	arg1	lectin					454:459	macrophage inducible C-type lectin	426:459	macrophage inducible C-type lectin receptor	426:468	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	2	84	theme	macrophage	426:435	arg1	lectin					454:459	macrophage inducible C-type lectin	426:459	macrophage inducible C-type lectin receptor	426:468	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	5	85	theme	SLPs	1031:1034	arg1	O-glycans					1008:1016	the O-glycans	1004:1016	the O-glycans of the three SLPs	1004:1034	High-performance anion-exchange chromatography-pulse amperometric detector performed after β-elimination showed glucose as the major component in the O-glycans of the three SLPs; however, some differences in the length of hexose chains were observed.
32817316	0	86	theme	distinct	64:71	arg1	patterns					87:94	distinct glycosylation patterns	64:94	distinct glycosylation patterns	64:94	Immunostimulation by Lactobacillus kefiri S-layer proteins with distinct glycosylation patterns requires different lectin partners.
32817316	6	87	contain	have	1205:1208	arg1	SLP-5818					1180:1187	SLP-5818	1180:1187	SLP-5818	1180:1187	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	6	87	contain	have	1205:1208	arg2	sites					1214:1218	two sites	1210:1218	two sites carrying complex N-glycans	1210:1245	No N-glycosylation signals were detected in SLP-8348 and SLP-8321, but SLP-5818 was observed to have two sites carrying complex N-glycans based on a site-specific analysis and a glycomic workflow of the permethylated glycans.
32817316	2	88	theme	Lactobacillus	358:370	arg1	8348					385:388	probiotic Lactobacillus kefiri CIDCA 8348	348:388	probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348)	348:399	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	2	88	theme	Lactobacillus	358:370	arg1	SLP-8348					391:398	SLP-8348	391:398	SLP-8348	391:398	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32817316	8	89	dep	SignR3	1841:1846	arg1	ortholog					1856:1863	murine ortholog	1849:1863	murine ortholog of human DC-SIGN	1849:1880	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	8	90	theme	marrow-derived	1628:1641	arg1	cells					1653:1657	bone marrow-derived dendritic cells	1623:1657	bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice	1623:1700	Studies performed with bone marrow-derived dendritic cells from C-type lectin receptor-deficient mice revealed that the immunostimulatory activity of SLP-8321 depends on its recognition by Mincle, whereas SLP-5818's effects are dependent on SignR3 (murine ortholog of human DC-SIGN).
32817316	4	91	theme	C-type	751:756	arg1	receptors					765:773	C-type lectin receptors	751:773	C-type lectin receptors	751:773	Herein, we analyze the glycosylation pattern of three SLPs, SLP-8348, SLP-8321, and SLP-5818, and explore how these patterns impact their recognition by C-type lectin receptors and the immunomodulatory effect of the L. kefiri SLPs on antigen-presenting cells.
32817316	1	92	theme	prokaryotes	232:242	arg1	surface					211:217	the surface	207:217	the surface of different prokaryotes	207:242	S-layer (glyco)-proteins (SLPs) form a nanostructured envelope that covers the surface of different prokaryotes and show immunomodulatory activity.
32817316	2	93	gly	glycoprotein	330:341	arg1	glycoprotein					330:341	the S-layer glycoprotein	318:341	the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348)	318:399	Previously, we have demonstrated that the S-layer glycoprotein from probiotic Lactobacillus kefiri CIDCA 8348 (SLP-8348) is recognized by Mincle (macrophage inducible C-type lectin receptor), and its adjuvanticity depends on the integrity of its glycans.
32236654	8	0	theme	sialyl	1287:1292	arg1	epitope					1304:1310	I-branched and sialyl Lewis x/a epitope	1272:1310	I-branched and sialyl Lewis x/a epitope carrying glycans	1272:1327	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	2	1	theme	cell	348:351	arg1	types					353:357	different cell types	338:357	different cell types	338:357	However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types.
32236654	8	2	theme	x/a	1300:1302	arg1	epitope					1304:1310	I-branched and sialyl Lewis x/a epitope	1272:1310	I-branched and sialyl Lewis x/a epitope carrying glycans	1272:1327	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	6	3	theme	Striking	999:1006	arg1	differences					1008:1018	Striking differences	999:1018	Striking differences	999:1018	Striking differences are observed between the O-glycomes of 26 CRC cell lines.
32236654	10	4	theme	cell	1751:1754	arg1	O-glycomes					1761:1770	cell line O-glycomes	1751:1770	cell line O-glycomes	1751:1770	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	3	5	theme	lines	556:560	arg1	analysis					522:529	an in-depth O-glycosylation analysis	494:529	an in-depth O-glycosylation analysis of 26 different CRC cell lines	494:560	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	5	6	with	Associations	838:849	arg1	signatures					939:948	previously reported cell line transcriptome signatures	895:948	previously reported cell line transcriptome signatures	895:948	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	3	7	theme	CRC	547:549	arg1	lines					556:560	26 different CRC cell lines	534:560	26 different CRC cell lines	534:560	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	8	8	theme	epitope	1391:1397	arg1	expression					1399:1408	Lewis epitope expression	1385:1408	Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans	1385:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	8	9	theme	most	1336:1339	arg1	lines					1363:1367	most undifferentiated cell lines	1336:1367	most undifferentiated cell lines	1336:1367	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	6	10	theme	cell	1066:1069	arg1	lines					1071:1075	26 CRC cell lines	1059:1075	26 CRC cell lines	1059:1075	Striking differences are observed between the O-glycomes of 26 CRC cell lines.
32236654	4	11	theme	chromatography	655:668	arg1	system					670:675	porous graphitized carbon nano-liquid chromatography system	617:675	porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization	617:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	10	12	theme	O-glycomes	1761:1770	arg1	screening					1738:1746	This untargeted in-depth screening	1713:1746	This untargeted in-depth screening of cell line O-glycomes	1713:1770	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	9	13	theme	glycan	1668:1673	arg1	biosynthesis					1675:1686	glycan biosynthesis	1668:1686	glycan biosynthesis	1668:1686	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	10	14	theme	anti-cancer	1939:1949	arg1	antibodies					1951:1960	anti-cancer antibodies	1939:1960	anti-cancer antibodies	1939:1960	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	5	15	theme	cell	915:918	arg1	signatures					939:948	previously reported cell line transcriptome signatures	895:948	previously reported cell line transcriptome signatures	895:948	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	8	16	theme	cell	1358:1361	arg1	lines					1363:1367	most undifferentiated cell lines	1336:1367	most undifferentiated cell lines	1336:1367	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	7	17	theme	cell	1201:1204	arg1	lines					1206:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines.
32236654	5	18	theme	transcriptome	925:937	arg1	signatures					939:948	previously reported cell line transcriptome signatures	895:948	previously reported cell line transcriptome signatures	895:948	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	8	19	theme	truncated	1436:1444	arg1	glycans					1467:1473	truncated α2,6-core sialylated glycans	1436:1473	truncated α2,6-core sialylated glycans	1436:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	8	20	theme	sialylated	1456:1465	arg1	glycans					1467:1473	truncated α2,6-core sialylated glycans	1436:1473	truncated α2,6-core sialylated glycans	1436:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	7	21	theme	well-differentiated	1149:1167	arg1	lines					1206:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines.
32236654	7	22	theme	principal	1091:1099	arg1	analysis					1111:1118	Unsupervized principal component analysis	1078:1118	Unsupervized principal component analysis	1078:1118	Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines.
32236654	9	23	theme	biosynthesis	1675:1686	arg1	regulation					1654:1663	the regulation	1650:1663	the regulation of glycan biosynthesis in different cell types	1650:1710	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	2	24	from	O-glycome	282:290	arg1	types					353:357	different cell types	338:357	different cell types	338:357	However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types.
32236654	2	24	from	O-glycome	282:290	arg1	biosynthesis					322:333	glycan biosynthesis	315:333	glycan biosynthesis	315:333	However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types.
32236654	4	25	theme	isomeric	769:776	arg1	separation					778:787	isomeric separation	769:787	isomeric separation as well as in-depth structural characterization	769:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	4	26	theme	electrospray	712:723	arg1	ionization					725:734	electrospray ionization	712:734	electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization	712:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	4	26	theme	electrospray	712:723	arg1	PGC-nano-LC-ESI-MS/MS					737:757	PGC-nano-LC-ESI-MS/MS	737:757	PGC-nano-LC-ESI-MS/MS	737:757	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	5	27	theme	correlation	977:987	arg1	analysis					989:996	canonical correlation analysis	967:996	canonical correlation analysis	967:996	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	3	28	from	variation	401:409	arg1	phenotypes					430:439	O-glycosylation phenotypes	414:439	O-glycosylation phenotypes	414:439	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	4	29	theme	structural	809:818	arg1	characterization					820:835	in-depth structural characterization	800:835	isomeric separation as well as in-depth structural characterization	769:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	0	30	theme	cellular	87:94	arg1	phenotype					112:120	the cellular differentiation phenotype	83:120	the cellular differentiation phenotype	83:120	Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
32236654	8	31	contain	carrying	1312:1319	arg2	glycans					1321:1327	glycans	1321:1327	glycans	1321:1327	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	8	31	contain	carrying	1312:1319	arg1	epitope					1304:1310	I-branched and sialyl Lewis x/a epitope	1272:1310	I-branched and sialyl Lewis x/a epitope carrying glycans	1272:1327	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	10	32	theme	glycosylation	1827:1839	arg1	role					1819:1822	the role	1815:1822	the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies	1815:1960	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	9	33	theme	deeper	1630:1635	arg1	insight					1637:1643	a deeper insight	1628:1643	a deeper insight into the regulation of glycan biosynthesis in different cell types	1628:1710	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	3	34	theme	better	373:378	arg1	understanding					380:392	a better understanding	371:392	a better understanding of the variation in O-glycosylation phenotypes	371:439	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	3	35	theme	O-glycosylation	414:428	arg1	phenotypes					430:439	O-glycosylation phenotypes	414:439	O-glycosylation phenotypes	414:439	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	0	36	theme	Colorectal	0:9	arg1	lines					23:27	Colorectal cancer cell lines	0:27	Colorectal cancer cell lines	0:27	Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
32236654	1	37	from	Alterations	123:133	arg1	glycosylation					146:158	protein glycosylation	138:158	protein glycosylation in colorectal cancer (CRC)	138:185	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	9	38	theme	different	1691:1699	arg1	types					1706:1710	different cell types	1691:1710	different cell types	1691:1710	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	3	39	theme	other	468:472	arg1	features					484:491	other molecular features	468:491	other molecular features	468:491	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	0	40	theme	cell	18:21	arg1	lines					23:27	Colorectal cancer cell lines	0:27	Colorectal cancer cell lines	0:27	Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
32236654	8	41	theme	Colon-like	1213:1222	arg1	lines					1229:1233	Colon-like cell lines	1213:1233	Colon-like cell lines	1213:1233	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	3	42	theme	variation	401:409	arg1	understanding					380:392	a better understanding	371:392	a better understanding of the variation in O-glycosylation phenotypes	371:439	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	3	42	theme	variation	401:409	arg1	association					451:461	their association	445:461	their association with other molecular features	445:491	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	10	43	theme	CRC	1844:1846	arg1	development					1848:1858	CRC development	1844:1858	CRC development	1844:1858	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	9	44	theme	signatures	1511:1520	arg1	expression					1490:1499	the expression	1486:1499	the expression of glycan signatures	1486:1520	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	10	45	from	role	1819:1822	arg1	development					1848:1858	CRC development	1844:1858	CRC development	1844:1858	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	10	45	from	role	1819:1822	arg1	response					1869:1876	drug response	1864:1876	drug response	1864:1876	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	2	46	theme	different	338:346	arg1	types					353:357	different cell types	338:357	different cell types	338:357	However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types.
32236654	5	47	theme	observed	863:870	arg1	phenotypes					879:888	the observed glycan phenotypes	859:888	the observed glycan phenotypes	859:888	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	1	48	theme	colorectal	163:172	arg1	CRC					182:184	CRC	182:184	CRC	182:184	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	1	48	theme	colorectal	163:172	arg1	cancer					174:179	colorectal cancer	163:179	colorectal cancer (CRC)	163:185	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	10	49	theme	in-depth	1729:1736	arg1	screening					1738:1746	This untargeted in-depth screening	1713:1746	This untargeted in-depth screening of cell line O-glycomes	1713:1770	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	3	50	from	phenotypes	430:439	arg1	understanding					380:392	a better understanding	371:392	a better understanding of the variation in O-glycosylation phenotypes	371:439	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	3	50	from	phenotypes	430:439	arg1	association					451:461	their association	445:461	their association with other molecular features	445:491	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	10	51	theme	targets	1908:1914	arg1	discovery					1889:1897	discovery	1889:1897	discovery of novel targets for the development of anti-cancer antibodies	1889:1960	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	9	52	theme	glycosyltransferases	1556:1575	arg1	expression					1542:1551	the expression	1538:1551	the expression of glycosyltransferases that are involved in their biosynthesis	1538:1615	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	4	53	theme	graphitized	624:634	arg1	chromatography					655:668	porous graphitized carbon nano-liquid chromatography	617:668	porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization	617:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	3	54	theme	O-glycosylation	506:520	arg1	analysis					522:529	an in-depth O-glycosylation analysis	494:529	an in-depth O-glycosylation analysis of 26 different CRC cell lines	494:560	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	4	55	theme	released	581:588	arg1	O-glycans					590:598	The released O-glycans	577:598	The released O-glycans	577:598	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	10	56	theme	line	1756:1759	arg1	O-glycomes					1761:1770	cell line O-glycomes	1751:1770	cell line O-glycomes	1751:1770	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	3	57	theme	cell	551:554	arg1	lines					556:560	26 different CRC cell lines	534:560	26 different CRC cell lines	534:560	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	8	58	theme	Lewis	1294:1298	arg1	epitope					1304:1310	I-branched and sialyl Lewis x/a epitope	1272:1310	I-branched and sialyl Lewis x/a epitope carrying glycans	1272:1327	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	3	59	theme	different	537:545	arg1	lines					556:560	26 different CRC cell lines	534:560	26 different CRC cell lines	534:560	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	8	60	theme	epitope	1304:1310	arg1	prevalence					1258:1267	a prevalence	1256:1267	a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans	1256:1327	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	6	61	theme	lines	1071:1075	arg1	O-glycomes					1045:1054	the O-glycomes	1041:1054	the O-glycomes of 26 CRC cell lines	1041:1075	Striking differences are observed between the O-glycomes of 26 CRC cell lines.
32236654	9	62	from	regulation	1654:1663	arg1	types					1706:1710	different cell types	1691:1710	different cell types	1691:1710	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	4	63	theme	mass	690:693	arg1	spectrometer					695:706	a mass spectrometer	688:706	a mass spectrometer	688:706	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	3	64	with	association	451:461	arg1	features					484:491	other molecular features	468:491	other molecular features	468:491	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	10	65	theme	antibodies	1951:1960	arg1	development					1924:1934	the development	1920:1934	the development of anti-cancer antibodies	1920:1960	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	5	66	theme	reported	906:913	arg1	signatures					939:948	previously reported cell line transcriptome signatures	895:948	previously reported cell line transcriptome signatures	895:948	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	6	67	theme	CRC	1062:1064	arg1	lines					1071:1075	26 CRC cell lines	1059:1075	26 CRC cell lines	1059:1075	Striking differences are observed between the O-glycomes of 26 CRC cell lines.
32236654	3	68	with	understanding	380:392	arg1	features					484:491	other molecular features	468:491	other molecular features	468:491	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	4	69	theme	nano-liquid	643:653	arg1	chromatography					655:668	porous graphitized carbon nano-liquid chromatography	617:668	porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization	617:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	1	70	gly	glycosylation	146:158	arg1	CRC					182:184	CRC	182:184	CRC	182:184	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	1	70	gly	glycosylation	146:158	arg1	cancer					174:179	colorectal cancer	163:179	colorectal cancer (CRC)	163:185	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	8	71	theme	Lewis	1385:1389	arg1	expression					1399:1408	Lewis epitope expression	1385:1408	Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans	1385:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	5	72	theme	line	920:923	arg1	signatures					939:948	previously reported cell line transcriptome signatures	895:948	previously reported cell line transcriptome signatures	895:948	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	8	73	theme	undifferentiated	1341:1356	arg1	lines					1363:1367	most undifferentiated cell lines	1336:1367	most undifferentiated cell lines	1336:1367	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	10	74	theme	future	1790:1795	arg1	studies					1797:1803	future studies	1790:1803	future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies	1790:1960	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	7	75	theme	colon-like	1169:1178	arg1	lines					1206:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines.
32236654	10	76	theme	novel	1902:1906	arg1	targets					1908:1914	novel targets	1902:1914	novel targets for the development of anti-cancer antibodies	1902:1960	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	10	77	gly	glycosylation	1827:1839	arg1	CRC					1844:1846	CRC development	1844:1858	CRC development	1844:1858	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	10	77	gly	glycosylation	1827:1839	arg1	drug					1864:1867	drug response	1864:1876	drug response	1864:1876	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	1	78	theme	protein	138:144	arg1	glycosylation					146:158	protein glycosylation	138:158	protein glycosylation in colorectal cancer (CRC)	138:185	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	8	79	theme	α2,6-core	1446:1454	arg1	glycans					1467:1473	truncated α2,6-core sialylated glycans	1436:1473	truncated α2,6-core sialylated glycans	1436:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	0	80	theme	O-glycome	62:70	arg1	diversity					43:51	striking diversity	34:51	striking diversity of their O-glycome reflecting the cellular differentiation phenotype	34:120	Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
32236654	7	81	theme	component	1101:1109	arg1	analysis					1111:1118	Unsupervized principal component analysis	1078:1118	Unsupervized principal component analysis	1078:1118	Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines.
32236654	5	82	theme	canonical	967:975	arg1	analysis					989:996	canonical correlation analysis	967:996	canonical correlation analysis	967:996	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	8	83	theme	glycans	1467:1473	arg1	dominance					1423:1431	dominance	1423:1431	dominance of truncated α2,6-core sialylated glycans	1423:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	7	84	theme	Unsupervized	1078:1089	arg1	analysis					1111:1118	Unsupervized principal component analysis	1078:1118	Unsupervized principal component analysis	1078:1118	Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines.
32236654	9	85	theme	cell	1701:1704	arg1	types					1706:1710	different cell types	1691:1710	different cell types	1691:1710	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	0	86	theme	differentiation	96:110	arg1	phenotype					112:120	the cellular differentiation phenotype	83:120	the cellular differentiation phenotype	83:120	Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
32236654	8	87	gly	sialylated	1456:1465	arg1	glycans					1467:1473	truncated α2,6-core sialylated glycans	1436:1473	truncated α2,6-core sialylated glycans	1436:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	2	88	from	differences	300:310	arg1	types					353:357	different cell types	338:357	different cell types	338:357	However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types.
32236654	2	88	from	differences	300:310	arg1	biosynthesis					322:333	glycan biosynthesis	315:333	glycan biosynthesis	315:333	However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types.
32236654	4	89	theme	in-depth	800:807	arg1	characterization					820:835	in-depth structural characterization	800:835	isomeric separation as well as in-depth structural characterization	769:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	10	90	theme	drug	1864:1867	arg1	response					1869:1876	drug response	1864:1876	drug response	1864:1876	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	8	91	theme	expression	1399:1408	arg1	absence					1374:1380	absence	1374:1380	absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans	1374:1473	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	3	92	gly	O-glycosylation	506:520	arg1	lines					556:560	26 different CRC cell lines	534:560	26 different CRC cell lines	534:560	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	5	93	theme	glycan	872:877	arg1	phenotypes					879:888	the observed glycan phenotypes	859:888	the observed glycan phenotypes	859:888	Associations between the observed glycan phenotypes with previously reported cell line transcriptome signatures were examined by canonical correlation analysis.
32236654	3	94	from	understanding	380:392	arg1	phenotypes					430:439	O-glycosylation phenotypes	414:439	O-glycosylation phenotypes	414:439	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	1	95	from	glycosylation	146:158	arg1	CRC					182:184	CRC	182:184	CRC	182:184	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	1	95	from	glycosylation	146:158	arg1	cancer					174:179	colorectal cancer	163:179	colorectal cancer (CRC)	163:185	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	7	96	theme	undifferentiated	1184:1199	arg1	lines					1206:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	well-differentiated colon-like and undifferentiated cell lines	1149:1210	Unsupervized principal component analysis reveals a separation between well-differentiated colon-like and undifferentiated cell lines.
32236654	8	97	theme	cell	1224:1227	arg1	lines					1229:1233	Colon-like cell lines	1213:1233	Colon-like cell lines	1213:1233	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	3	98	theme	molecular	474:482	arg1	features					484:491	other molecular features	468:491	other molecular features	468:491	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	0	99	theme	striking	34:41	arg1	diversity					43:51	striking diversity	34:51	striking diversity of their O-glycome reflecting the cellular differentiation phenotype	34:120	Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
32236654	9	100	theme	glycan	1504:1509	arg1	signatures					1511:1520	glycan signatures	1504:1520	glycan signatures	1504:1520	Moreover, the expression of glycan signatures associates with the expression of glycosyltransferases that are involved in their biosynthesis, providing a deeper insight into the regulation of glycan biosynthesis in different cell types.
32236654	3	101	from	association	451:461	arg1	phenotypes					430:439	O-glycosylation phenotypes	414:439	O-glycosylation phenotypes	414:439	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	3	102	theme	in-depth	497:504	arg1	analysis					522:529	an in-depth O-glycosylation analysis	494:529	an in-depth O-glycosylation analysis of 26 different CRC cell lines	494:560	To provide a better understanding of the variation in O-glycosylation phenotypes and their association with other molecular features, an in-depth O-glycosylation analysis of 26 different CRC cell lines was performed.
32236654	4	103	theme	porous	617:622	arg1	chromatography					655:668	porous graphitized carbon nano-liquid chromatography	617:668	porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization	617:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	2	104	theme	glycan	315:320	arg1	biosynthesis					322:333	glycan biosynthesis	315:333	glycan biosynthesis	315:333	However, little is known about their O-glycome and the differences in glycan biosynthesis in different cell types.
32236654	8	105	theme	I-branched	1272:1281	arg1	epitope					1304:1310	I-branched and sialyl Lewis x/a epitope	1272:1310	I-branched and sialyl Lewis x/a epitope carrying glycans	1272:1327	Colon-like cell lines are characterized by a prevalence of I-branched and sialyl Lewis x/a epitope carrying glycans, while most undifferentiated cell lines show absence of Lewis epitope expression resulting in dominance of truncated α2,6-core sialylated glycans.
32236654	1	106	theme	cell	223:226	arg1	models					237:242	models	237:242	models	237:242	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	1	106	theme	cell	223:226	arg1	lines					228:232	cell lines	223:232	cell lines	223:232	Alterations in protein glycosylation in colorectal cancer (CRC) have been extensively studied using cell lines as models.
32236654	4	107	theme	carbon	636:641	arg1	chromatography					655:668	porous graphitized carbon nano-liquid chromatography	617:668	porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization	617:835	The released O-glycans were analysed on porous graphitized carbon nano-liquid chromatography system coupled to a mass spectrometer via electrospray ionization (PGC-nano-LC-ESI-MS/MS) allowing isomeric separation as well as in-depth structural characterization.
32236654	10	108	theme	untargeted	1718:1727	arg1	screening					1738:1746	This untargeted in-depth screening	1713:1746	This untargeted in-depth screening of cell line O-glycomes	1713:1770	This untargeted in-depth screening of cell line O-glycomes paves the way for future studies exploring the role of glycosylation in CRC development and drug response leading to discovery of novel targets for the development of anti-cancer antibodies.
32236654	0	109	theme	cancer	11:16	arg1	lines					23:27	Colorectal cancer cell lines	0:27	Colorectal cancer cell lines	0:27	Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype.
33171078	6	0	theme	human	1449:1453	arg1	glycans					1455:1461	the human glycans	1445:1461	the human glycans	1445:1461	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	7	1	theme	relative	1468:1475	arg1	proportions					1477:1487	The relative proportions	1464:1487	The relative proportions of the glycans	1464:1502	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
33171078	4	2	theme	study	830:834	arg1	participants					836:847	clinical study participants	821:847	clinical study participants	821:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	6	3	theme	same	1267:1270	arg1	day					1272:1274	the same day	1263:1274	the same day	1263:1274	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	4	4	from	impact	647:652	arg1	clearance					694:702	in vivo clearance	686:702	in vivo clearance	686:702	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	1	5	theme	agents	234:239	arg1	safety					205:210	safety	205:210	safety	205:210	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	1	5	theme	agents	234:239	arg1	efficacy					216:223	efficacy	216:223	efficacy	216:223	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	4	6	theme	human	786:790	arg1	samples					798:804	human serum samples	786:804	human serum samples collected from clinical study participants	786:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	3	7	theme	glycan	486:491	arg1	structures					493:502	Immunogenic glycan structures	474:502	Immunogenic glycan structures	474:502	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	1	8	theme	therapeutic	149:159	arg1	mAbs					184:187	mAbs	184:187	mAbs	184:187	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	1	8	theme	therapeutic	149:159	arg1	antibodies					172:181	therapeutic monoclonal antibodies	149:181	therapeutic monoclonal antibodies (mAbs)	149:188	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	6	9	theme	human	1248:1252	arg1	serum					1254:1258	human serum	1248:1258	human serum	1248:1258	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	2	10	theme	nonhuman	268:275	arg1	origin					277:282	nonhuman origin	268:282	nonhuman origin	268:282	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	5	11	theme	separation	899:908	arg1	process					910:916	a three-step chromatographic separation process	870:916	a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography)	870:1010	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	0	12	theme	NS0	96:98	arg1	line					105:108	NS0 cell line	96:108	NS0 cell line	96:108	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	3	13	theme	immune-mediated	513:527	arg1	clearance					529:537	immune-mediated clearance	513:537	immune-mediated clearance	513:537	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	3	14	dep	in	575:576	arg1	vivo					578:581	vivo	578:581	vivo	578:581	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	7	15	theme	year	1608:1611	arg1	course					1596:1601	the course	1592:1601	the course of a year	1592:1611	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
33171078	6	16	theme	significant	1313:1323	arg1	differences					1325:1335	no significant differences	1310:1335	no significant differences	1310:1335	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	6	17	theme	mAb1	1228:1231	arg1	profile					1217:1223	the glycan profile	1206:1223	the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing	1206:1299	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	6	18	theme	profile	1217:1223	arg1	comparison					1192:1201	A comparison	1190:1201	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing	1190:1299	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	5	19	theme	three-step	872:881	arg1	process					910:916	a three-step chromatographic separation process	870:916	a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography)	870:1010	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	7	20	theme	immune	1699:1704	arg1	response					1706:1713	an immune response	1696:1713	an immune response	1696:1713	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
33171078	7	21	theme	mAb1	1582:1585	arg1	doses					1573:1577	multiple doses	1564:1577	multiple doses of mAb1	1564:1585	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
33171078	5	22	dep	process	910:916	arg1	affinity					961:968	immobilized anti-mAb1 antibody affinity	930:968	immobilized anti-mAb1 antibody affinity	930:968	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	22	dep	process	910:916	arg1	A					927:927	protein A	919:927	protein A	919:927	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	22	dep	process	910:916	arg1	chromatography					996:1009	weak cation exchange chromatography	975:1009	weak cation exchange chromatography	975:1009	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	3	23	theme	in	575:576	arg1	circulation					583:593	in vivo circulation	575:593	in vivo circulation than non-immunogenic structures	575:625	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	6	24	with	mAb1	1370:1373	arg1	NGNA					1402:1405	NGNA	1402:1405	NGNA	1402:1405	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	6	24	with	mAb1	1370:1373	arg1	gal-α-gal					1389:1397	gal-α-gal	1389:1397	gal-α-gal	1389:1397	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	4	25	theme	nonhuman	666:673	arg1	glycans					675:681	these Fc nonhuman glycans	657:681	these Fc nonhuman glycans	657:681	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	1	26	theme	glycosylation	132:144	arg1	heterogeneity					115:127	The heterogeneity	111:127	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs)	111:188	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	0	27	from	Impact	0:5	arg1	clearance					41:49	in vivo clearance	33:49	in vivo clearance of an immunoglobulin G1 antibody	33:82	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	0	28	theme	G1	72:73	arg1	antibody					75:82	an immunoglobulin G1 antibody	54:82	an immunoglobulin G1 antibody	54:82	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	4	29	from	samples	798:804	arg1	profile					741:747	the glycan profile	730:747	the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants	730:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	4	29	from	samples	798:804	arg1	mAb1					775:778	mAb1	775:778	mAb1	775:778	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	4	29	from	samples	798:804	arg1	antibody					765:772	a monoclonal antibody	752:772	a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants	752:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	8	30	theme	low	1792:1794	arg1	risk					1796:1799	a low risk	1790:1799	a low risk of conferring immunogenicity	1790:1828	Therefore, we concluded that mAb1 gal-α-gal and NGNA glycoforms represent a low risk of conferring immunogenicity.
33171078	4	31	theme	glycan	734:739	arg1	profile					741:747	the glycan profile	730:747	the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants	730:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	6	32	theme	similar	1349:1355	arg1	clearance					1357:1365	similar clearance	1349:1365	similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region	1349:1429	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	5	33	theme	immobilized	930:940	arg1	affinity					961:968	immobilized anti-mAb1 antibody affinity	930:968	immobilized anti-mAb1 antibody affinity	930:968	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	2	34	theme	therapeutic	393:403	arg1	mAbs					405:408	therapeutic mAbs	393:408	therapeutic mAbs produced from murine cell lines	393:440	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	3	35	from	circulation	583:593	arg1	clearance					560:568	faster clearance	553:568	faster clearance from in vivo circulation than non-immunogenic structures	553:625	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	6	36	dep	gal-α-gal	1389:1397	arg1	glycan					1407:1412	glycan	1407:1412	glycan	1407:1412	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	5	37	from	mAb1	862:865	arg1	process					910:916	a three-step chromatographic separation process	870:916	a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography)	870:1010	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	4	38	dep	in	686:687	arg1	vivo					689:692	vivo	689:692	vivo	689:692	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	3	39	contain	have	508:511	arg1	structures					493:502	Immunogenic glycan structures	474:502	Immunogenic glycan structures	474:502	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	3	39	contain	have	508:511	arg2	clearance					529:537	immune-mediated clearance	513:537	immune-mediated clearance	513:537	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	6	40	theme	Fc	1421:1422	arg1	region					1424:1429	the Fc region	1417:1429	the Fc region	1417:1429	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	2	41	theme	murine	424:429	arg1	lines					436:440	murine cell lines	424:440	murine cell lines	424:440	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	0	42	theme	glycans	22:28	arg1	Impact					0:5	Impact	0:5	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody	0:82	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	5	43	theme	ultrahigh-performance	1121:1141	arg1	chromatography					1174:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	0	44	dep	in	33:34	arg1	vivo					36:39	vivo	36:39	vivo	36:39	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	0	45	theme	Fc	10:11	arg1	glycans					22:28	Fc N-linked glycans	10:28	Fc N-linked glycans	10:28	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	3	46	theme	non-immunogenic	600:614	arg1	structures					616:625	non-immunogenic structures	600:625	non-immunogenic structures	600:625	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	0	47	theme	in	33:34	arg1	clearance					41:49	in vivo clearance	33:49	in vivo clearance of an immunoglobulin G1 antibody	33:82	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	5	48	theme	interaction	1155:1165	arg1	chromatography					1174:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	49	theme	exchange	987:994	arg1	chromatography					996:1009	weak cation exchange chromatography	975:1009	weak cation exchange chromatography	975:1009	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	50	theme	weak	975:978	arg1	chromatography					996:1009	weak cation exchange chromatography	975:1009	weak cation exchange chromatography	975:1009	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	51	theme	antibody	952:959	arg1	affinity					961:968	immobilized anti-mAb1 antibody affinity	930:968	immobilized anti-mAb1 antibody affinity	930:968	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	8	52	dep	gal-α-gal	1750:1758	arg1	glycoforms					1769:1778	glycoforms	1769:1778	glycoforms	1769:1778	Therefore, we concluded that mAb1 gal-α-gal and NGNA glycoforms represent a low risk of conferring immunogenicity.
33171078	4	53	theme	monoclonal	754:763	arg1	mAb1					775:778	mAb1	775:778	mAb1	775:778	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	4	53	theme	monoclonal	754:763	arg1	antibody					765:772	a monoclonal antibody	752:772	a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants	752:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	0	54	link	N-linked	13:20	arg1	glycans					22:28	Fc N-linked glycans	10:28	Fc N-linked glycans	10:28	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	4	55	theme	clinical	821:828	arg1	participants					836:847	clinical study participants	821:847	clinical study participants	821:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	5	56	link	N-linked	1042:1049	arg1	structures					1067:1076	its N-linked oligosaccharide structures	1038:1076	its N-linked oligosaccharide structures	1038:1076	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	3	57	theme	Immunogenic	474:484	arg1	structures					493:502	Immunogenic glycan structures	474:502	Immunogenic glycan structures	474:502	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	2	58	theme	origin	277:282	arg1	galactose-alpha-1,3-galactose					293:321	galactose-alpha-1,3-galactose	293:321	galactose-alpha-1,3-galactose (gal-α-gal)	293:333	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	58	theme	origin	277:282	arg1	acid					360:363	N-glycolylneuraminic acid	339:363	N-glycolylneuraminic acid (NGNA)	339:370	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	58	theme	origin	277:282	arg1	glycans					257:263	glycans	257:263	glycans	257:263	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	1	59	theme	monoclonal	161:170	arg1	mAbs					184:187	mAbs	184:187	mAbs	184:187	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	1	59	theme	monoclonal	161:170	arg1	antibodies					172:181	therapeutic monoclonal antibodies	149:181	therapeutic monoclonal antibodies (mAbs)	149:188	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	4	60	theme	serum	792:796	arg1	samples					798:804	human serum samples	786:804	human serum samples collected from clinical study participants	786:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	0	61	theme	cell	100:103	arg1	line					105:108	NS0 cell line	96:108	NS0 cell line	96:108	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	3	62	theme	faster	553:558	arg1	clearance					560:568	faster clearance	553:568	faster clearance from in vivo circulation than non-immunogenic structures	553:625	Immunogenic glycan structures can have immune-mediated clearance, resulting in faster clearance from in vivo circulation than non-immunogenic structures.
33171078	6	63	theme	mAb1	1370:1373	arg1	clearance					1357:1365	similar clearance	1349:1365	similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region	1349:1429	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	1	64	gly	heterogeneity	115:127	arg1	glycosylation					132:144	glycosylation	132:144	glycosylation	132:144	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	5	65	theme	N-linked	1042:1049	arg1	structures					1067:1076	its N-linked oligosaccharide structures	1038:1076	its N-linked oligosaccharide structures	1038:1076	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	4	66	theme	glycans	675:681	arg1	impact					647:652	the impact	643:652	the impact of these Fc nonhuman glycans on in vivo clearance	643:702	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	6	67	theme	glycan	1210:1215	arg1	profile					1217:1223	the glycan profile	1206:1223	the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing	1206:1299	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	4	68	theme	in	686:687	arg1	clearance					694:702	in vivo clearance	686:702	in vivo clearance	686:702	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	7	69	theme	multiple	1564:1571	arg1	doses					1573:1577	multiple doses	1564:1577	multiple doses of mAb1	1564:1585	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
33171078	0	70	theme	immunoglobulin	57:70	arg1	antibody					75:82	an immunoglobulin G1 antibody	54:82	an immunoglobulin G1 antibody	54:82	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	4	71	from	profile	741:747	arg1	samples					798:804	human serum samples	786:804	human serum samples collected from clinical study participants	786:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	2	72	from	glycans	257:263	arg1	region					383:388	the Fc region	376:388	the Fc region of therapeutic mAbs produced from murine cell lines	376:440	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	73	theme	cell	431:434	arg1	lines					436:440	murine cell lines	424:440	murine cell lines	424:440	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	4	74	theme	Fc	663:664	arg1	glycans					675:681	these Fc nonhuman glycans	657:681	these Fc nonhuman glycans	657:681	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	0	75	theme	antibody	75:82	arg1	clearance					41:49	in vivo clearance	33:49	in vivo clearance of an immunoglobulin G1 antibody	33:82	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	5	76	theme	protein	919:925	arg1	A					927:927	protein A	919:927	protein A	919:927	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	7	77	theme	glycans	1680:1686	arg1	none					1668:1671	none	1668:1671	none of the glycans	1668:1686	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
33171078	2	78	theme	immunogenicity	458:471	arg1	risk					450:453	a risk	448:453	a risk of immunogenicity	448:471	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	1	79	from	heterogeneity	115:127	arg1	mAbs					184:187	mAbs	184:187	mAbs	184:187	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	1	79	from	heterogeneity	115:127	arg1	antibodies					172:181	therapeutic monoclonal antibodies	149:181	therapeutic monoclonal antibodies (mAbs)	149:188	The heterogeneity of glycosylation on therapeutic monoclonal antibodies (mAbs) may affect the safety and efficacy of these agents.
33171078	5	80	theme	2-aminobenzamide	1083:1098	arg1	acid					1100:1103	2-aminobenzamide acid	1083:1103	2-aminobenzamide acid	1083:1103	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	81	theme	chromatographic	883:897	arg1	process					910:916	a three-step chromatographic separation process	870:916	a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography)	870:1010	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	2	82	theme	N-glycolylneuraminic	339:358	arg1	NGNA					366:369	NGNA	366:369	NGNA	366:369	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	82	theme	N-glycolylneuraminic	339:358	arg1	acid					360:363	N-glycolylneuraminic acid	339:363	N-glycolylneuraminic acid (NGNA)	339:370	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	0	83	theme	N-linked	13:20	arg1	glycans					22:28	Fc N-linked glycans	10:28	Fc N-linked glycans	10:28	Impact of Fc N-linked glycans on in vivo clearance of an immunoglobulin G1 antibody produced by NS0 cell line.
33171078	2	84	theme	Fc	380:381	arg1	region					383:388	the Fc region	376:388	the Fc region of therapeutic mAbs produced from murine cell lines	376:440	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	5	85	from	analysis	1109:1116	arg1	chromatography					1174:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	7	86	theme	antidrug	1631:1638	arg1	antibodies					1640:1649	antidrug antibodies	1631:1649	antidrug antibodies	1631:1649	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
33171078	4	87	theme	antibody	765:772	arg1	profile					741:747	the glycan profile	730:747	the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants	730:847	To demonstrate the impact of these Fc nonhuman glycans on in vivo clearance, we purified and analyzed the glycan profile of a monoclonal antibody (mAb1) from human serum samples collected from clinical study participants.
33171078	5	88	theme	hydrophilic	1143:1153	arg1	chromatography					1174:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	89	theme	oligosaccharide	1051:1065	arg1	structures					1067:1076	its N-linked oligosaccharide structures	1038:1076	its N-linked oligosaccharide structures	1038:1076	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	90	theme	cation	980:985	arg1	chromatography					996:1009	weak cation exchange chromatography	975:1009	weak cation exchange chromatography	975:1009	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	2	91	theme	mAbs	405:408	arg1	region					383:388	the Fc region	376:388	the Fc region of therapeutic mAbs produced from murine cell lines	376:440	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	92	contain	carry	442:446	arg3	particular					245:254	particular	245:254	particular	245:254	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	92	contain	carry	442:446	arg1	galactose-alpha-1,3-galactose					293:321	galactose-alpha-1,3-galactose	293:321	galactose-alpha-1,3-galactose (gal-α-gal)	293:333	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	92	contain	carry	442:446	arg2	risk					450:453	a risk	448:453	a risk of immunogenicity	448:471	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	92	contain	carry	442:446	arg1	glycans					257:263	glycans	257:263	glycans	257:263	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	2	92	contain	carry	442:446	arg1	acid					360:363	N-glycolylneuraminic acid	339:363	N-glycolylneuraminic acid (NGNA)	339:370	In particular, glycans of nonhuman origin, such as galactose-alpha-1,3-galactose (gal-α-gal) and N-glycolylneuraminic acid (NGNA), in the Fc region of therapeutic mAbs produced from murine cell lines carry a risk of immunogenicity.
33171078	5	93	theme	liquid	1167:1172	arg1	chromatography					1174:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	ultrahigh-performance hydrophilic interaction liquid chromatography	1121:1187	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	5	94	theme	anti-mAb1	942:950	arg1	affinity					961:968	immobilized anti-mAb1 antibody affinity	930:968	immobilized anti-mAb1 antibody affinity	930:968	We purified mAb1 in a three-step chromatographic separation process (protein A, immobilized anti-mAb1 antibody affinity, and weak cation exchange chromatography) and extracted and labeled its N-linked oligosaccharide structures with 2-aminobenzamide acid for analysis on ultrahigh-performance hydrophilic interaction liquid chromatography.
33171078	6	95	from	clearance	1357:1365	arg1	region					1424:1429	the Fc region	1417:1429	the Fc region	1417:1429	A comparison of the glycan profile of mAb1 recovered from human serum on the same day and 4 weeks after dosing revealed no significant differences, indicating similar clearance of mAb1 with nonhuman gal-α-gal or NGNA glycan in the Fc region compared with the human glycans.
33171078	7	96	theme	glycans	1496:1502	arg1	proportions					1477:1487	The relative proportions	1464:1487	The relative proportions of the glycans	1464:1502	The relative proportions of the glycans remained similar, and all patients who had already received multiple doses of mAb1 over the course of a year were negative for antidrug antibodies, suggesting that none of the glycans induced an immune response.
34132263	8	0	theme	μPAC	1033:1036	arg1	use					1019:1021	The use	1015:1021	The use of 200 cm μPAC	1015:1036	The use of 200 cm μPAC was also investigated for the permethylated glycan analysis.
34132263	4	1	theme	μPAC	674:677	arg1	viability					657:665	the viability	653:665	the viability of the μPAC for the analysis of permethylated glycans	653:719	Owing to its advantages such as low back pressure, reproducibility, and durability, we have investigated the viability of the μPAC for the analysis of permethylated glycans.
34132263	6	2	theme	cm	874:875	arg1	μPAC					877:880	the 50 cm μPAC	867:880	the 50 cm μPAC	867:880	We also found that the 50 cm μPAC can be used for the analysis of both permethylated N- and O-glycans.
34132263	9	3	theme	200	1099:1101	arg1	cm					1103:1104	cm	1103:1104	cm	1103:1104	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	6	4	theme	O-glycans	940:948	arg1	analysis					902:909	the analysis	898:909	the analysis of both permethylated N- and O-glycans	898:948	We also found that the 50 cm μPAC can be used for the analysis of both permethylated N- and O-glycans.
34132263	0	5	theme	glycans	74:80	arg1	analysis					48:55	the analysis	44:55	the analysis of permethylated glycans	44:80	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	9	6	theme	cm	1103:1104	arg1	μPAC					1106:1109	200 cm μPAC	1099:1109	200 cm μPAC	1099:1109	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	4	7	theme	low	580:582	arg1	pressure					589:596	low back pressure	580:596	low back pressure	580:596	Owing to its advantages such as low back pressure, reproducibility, and durability, we have investigated the viability of the μPAC for the analysis of permethylated glycans.
34132263	0	8	theme	permethylated	60:72	arg1	glycans					74:80	permethylated glycans	60:80	permethylated glycans	60:80	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	6	9	theme	N-	933:934	arg1	analysis					902:909	the analysis	898:909	the analysis of both permethylated N- and O-glycans	898:948	We also found that the 50 cm μPAC can be used for the analysis of both permethylated N- and O-glycans.
34132263	5	10	theme	trapping	831:838	arg1	column					840:845	PepMap trapping column	824:845	PepMap trapping column	824:845	In this work, we demonstrate the online purification ability of μPAC trapping column compared against PepMap trapping column.
34132263	3	11	theme	packed	338:343	arg1	columns					359:365	bed packed reverse phase columns	334:365	bed packed reverse phase columns	334:365	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	4	12	theme	glycans	713:719	arg1	analysis					687:694	the analysis	683:694	the analysis of permethylated glycans	683:719	Owing to its advantages such as low back pressure, reproducibility, and durability, we have investigated the viability of the μPAC for the analysis of permethylated glycans.
34132263	1	13	theme	proteins	156:163	arg1	modification					140:151	a complex and common post-translational modification	100:151	a complex and common post-translational modification of proteins	100:163	Glycosylation is a complex and common post-translational modification of proteins.
34132263	1	13	theme	proteins	156:163	arg1	Glycosylation					83:95	Glycosylation	83:95	Glycosylation	83:95	Glycosylation is a complex and common post-translational modification of proteins.
34132263	3	14	theme	reverse	345:351	arg1	columns					359:365	bed packed reverse phase columns	334:365	bed packed reverse phase columns	334:365	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	9	15	theme	efficient	1124:1132	arg1	separation					1134:1143	efficient separation	1124:1143	efficient separation of oligomannose glycan isomers as well as other complex glycans	1124:1207	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	2	16	used	used	247:250	arg2	spectrometry					217:228	liquid chromatography-mass spectrometry	190:228	liquid chromatography-mass spectrometry (LC-MS)	190:236	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	2	16	used	used	247:250	arg2	LC-MS					231:235	LC-MS	231:235	LC-MS	231:235	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	0	17	theme	micro	6:10	arg1	μPAC					34:37	μPAC	34:37	μPAC	34:37	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	0	17	theme	micro	6:10	arg1	columns					25:31	micro pillar array columns	6:31	micro pillar array columns (μPAC)	6:38	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	2	18	theme	biological	308:317	arg1	systems					319:325	biological systems	308:325	biological systems	308:325	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	3	19	theme	glycans	427:433	arg1	separation					399:408	the separation	395:408	the separation of permethylated glycans	395:433	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	6	20	theme	permethylated	919:931	arg1	N-					933:934	permethylated N-	919:934	permethylated N-	919:934	We also found that the 50 cm μPAC can be used for the analysis of both permethylated N- and O-glycans.
34132263	4	21	theme	permethylated	699:711	arg1	glycans					713:719	permethylated glycans	699:719	permethylated glycans	699:719	Owing to its advantages such as low back pressure, reproducibility, and durability, we have investigated the viability of the μPAC for the analysis of permethylated glycans.
34132263	0	22	theme	array	19:23	arg1	μPAC					34:37	μPAC	34:37	μPAC	34:37	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	0	22	theme	array	19:23	arg1	columns					25:31	micro pillar array columns	6:31	micro pillar array columns (μPAC)	6:38	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	7	23	theme	previous	998:1005	arg1	method					1007:1012	the previous method	994:1012	the previous method	994:1012	The use of 50 cm μPAC was compared against the previous method.
34132263	9	24	theme	oligomannose	1148:1159	arg1	isomers					1168:1174	oligomannose glycan isomers	1148:1174	oligomannose glycan isomers as well as other complex glycans	1148:1207	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	3	25	theme	commercialized	453:466	arg1	μPAC					503:506	μPAC	503:506	μPAC	503:506	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	3	25	theme	commercialized	453:466	arg1	columns					494:500	newly commercialized micro array pillar nanoLC columns	447:500	newly commercialized micro array pillar nanoLC columns (μPAC)	447:507	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	0	26	theme	pillar	12:17	arg1	μPAC					34:37	μPAC	34:37	μPAC	34:37	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	0	26	theme	pillar	12:17	arg1	columns					25:31	micro pillar array columns	6:31	micro pillar array columns (μPAC)	6:38	Using micro pillar array columns (μPAC) for the analysis of permethylated glycans.
34132263	6	27	used	used	889:892	arg2	μPAC					877:880	the 50 cm μPAC	867:880	the 50 cm μPAC	867:880	We also found that the 50 cm μPAC can be used for the analysis of both permethylated N- and O-glycans.
34132263	9	28	theme	glycan	1161:1166	arg1	isomers					1168:1174	oligomannose glycan isomers	1148:1174	oligomannose glycan isomers as well as other complex glycans	1148:1207	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	3	29	theme	micro	468:472	arg1	μPAC					503:506	μPAC	503:506	μPAC	503:506	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	3	29	theme	micro	468:472	arg1	columns					494:500	newly commercialized micro array pillar nanoLC columns	447:500	newly commercialized micro array pillar nanoLC columns (μPAC)	447:507	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	9	30	theme	isomers	1168:1174	arg1	separation					1134:1143	efficient separation	1124:1143	efficient separation of oligomannose glycan isomers as well as other complex glycans	1124:1207	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	3	31	theme	permethylated	413:425	arg1	glycans					427:433	permethylated glycans	413:433	permethylated glycans	413:433	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	3	32	used	utilized	382:389	arg2	columns					359:365	bed packed reverse phase columns	334:365	bed packed reverse phase columns	334:365	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	5	33	theme	μPAC	786:789	arg1	column					800:805	μPAC trapping column	786:805	μPAC trapping column	786:805	In this work, we demonstrate the online purification ability of μPAC trapping column compared against PepMap trapping column.
34132263	5	34	theme	PepMap	824:829	arg1	column					840:845	PepMap trapping column	824:845	PepMap trapping column	824:845	In this work, we demonstrate the online purification ability of μPAC trapping column compared against PepMap trapping column.
34132263	5	35	theme	online	755:760	arg1	ability					775:781	the online purification ability	751:781	the online purification ability of μPAC trapping column compared against PepMap trapping column	751:845	In this work, we demonstrate the online purification ability of μPAC trapping column compared against PepMap trapping column.
34132263	3	36	theme	phase	353:357	arg1	columns					359:365	bed packed reverse phase columns	334:365	bed packed reverse phase columns	334:365	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	8	37	theme	cm	1030:1031	arg1	μPAC					1033:1036	200 cm μPAC	1026:1036	200 cm μPAC	1026:1036	The use of 200 cm μPAC was also investigated for the permethylated glycan analysis.
34132263	7	38	theme	50	962:963	arg1	cm					965:966	cm	965:966	cm	965:966	The use of 50 cm μPAC was compared against the previous method.
34132263	3	39	theme	nanoLC	487:492	arg1	μPAC					503:506	μPAC	503:506	μPAC	503:506	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	3	39	theme	nanoLC	487:492	arg1	columns					494:500	newly commercialized micro array pillar nanoLC columns	447:500	newly commercialized micro array pillar nanoLC columns (μPAC)	447:507	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	5	40	theme	purification	762:773	arg1	ability					775:781	the online purification ability	751:781	the online purification ability of μPAC trapping column compared against PepMap trapping column	751:845	In this work, we demonstrate the online purification ability of μPAC trapping column compared against PepMap trapping column.
34132263	8	41	theme	200	1026:1028	arg1	cm					1030:1031	cm	1030:1031	cm	1030:1031	The use of 200 cm μPAC was also investigated for the permethylated glycan analysis.
34132263	2	42	theme	chromatography-mass	197:215	arg1	LC-MS					231:235	LC-MS	231:235	LC-MS	231:235	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	2	42	theme	chromatography-mass	197:215	arg1	spectrometry					217:228	liquid chromatography-mass spectrometry	190:228	liquid chromatography-mass spectrometry (LC-MS)	190:236	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	9	43	theme	other	1187:1191	arg1	glycans					1201:1207	other complex glycans	1187:1207	oligomannose glycan isomers as well as other complex glycans	1148:1207	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	3	44	theme	columns	494:500	arg1	use					440:442	the use	436:442	the use of newly commercialized micro array pillar nanoLC columns (μPAC)	436:507	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	7	45	theme	cm	965:966	arg1	μPAC					968:971	50 cm μPAC	962:971	50 cm μPAC	962:971	The use of 50 cm μPAC was compared against the previous method.
34132263	2	46	theme	liquid	190:195	arg1	LC-MS					231:235	LC-MS	231:235	LC-MS	231:235	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	2	46	theme	liquid	190:195	arg1	spectrometry					217:228	liquid chromatography-mass spectrometry	190:228	liquid chromatography-mass spectrometry (LC-MS)	190:236	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	1	47	theme	complex	102:108	arg1	modification					140:151	a complex and common post-translational modification	100:151	a complex and common post-translational modification of proteins	100:163	Glycosylation is a complex and common post-translational modification of proteins.
34132263	1	47	theme	complex	102:108	arg1	Glycosylation					83:95	Glycosylation	83:95	Glycosylation	83:95	Glycosylation is a complex and common post-translational modification of proteins.
34132263	8	48	theme	glycan	1082:1087	arg1	analysis					1089:1096	the permethylated glycan analysis	1064:1096	the permethylated glycan analysis	1064:1096	The use of 200 cm μPAC was also investigated for the permethylated glycan analysis.
34132263	7	49	theme	μPAC	968:971	arg1	use					955:957	The use	951:957	The use of 50 cm μPAC	951:971	The use of 50 cm μPAC was compared against the previous method.
34132263	9	50	theme	complex	1193:1199	arg1	glycans					1201:1207	other complex glycans	1187:1207	oligomannose glycan isomers as well as other complex glycans	1148:1207	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	3	51	theme	pillar	480:485	arg1	μPAC					503:506	μPAC	503:506	μPAC	503:506	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	3	51	theme	pillar	480:485	arg1	columns					494:500	newly commercialized micro array pillar nanoLC columns	447:500	newly commercialized micro array pillar nanoLC columns (μPAC)	447:507	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	3	52	theme	array	474:478	arg1	μPAC					503:506	μPAC	503:506	μPAC	503:506	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	3	52	theme	array	474:478	arg1	columns					494:500	newly commercialized micro array pillar nanoLC columns	447:500	newly commercialized micro array pillar nanoLC columns (μPAC)	447:507	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	9	53	theme	glycans	1201:1207	arg1	separation					1134:1143	efficient separation	1124:1143	efficient separation of oligomannose glycan isomers as well as other complex glycans	1124:1207	200 cm μPAC demonstrated efficient separation of oligomannose glycan isomers as well as other complex glycans.
34132263	5	54	theme	column	800:805	arg1	ability					775:781	the online purification ability	751:781	the online purification ability of μPAC trapping column compared against PepMap trapping column	751:845	In this work, we demonstrate the online purification ability of μPAC trapping column compared against PepMap trapping column.
34132263	1	55	theme	common	114:119	arg1	modification					140:151	a complex and common post-translational modification	100:151	a complex and common post-translational modification of proteins	100:163	Glycosylation is a complex and common post-translational modification of proteins.
34132263	1	55	theme	common	114:119	arg1	Glycosylation					83:95	Glycosylation	83:95	Glycosylation	83:95	Glycosylation is a complex and common post-translational modification of proteins.
34132263	3	56	theme	bed	334:336	arg1	columns					359:365	bed packed reverse phase columns	334:365	bed packed reverse phase columns	334:365	While bed packed reverse phase columns are frequently utilized for the separation of permethylated glycans, the use of newly commercialized micro array pillar nanoLC columns (μPAC) have not been demonstrated previously.
34132263	5	57	theme	trapping	791:798	arg1	column					800:805	μPAC trapping column	786:805	μPAC trapping column	786:805	In this work, we demonstrate the online purification ability of μPAC trapping column compared against PepMap trapping column.
34132263	1	58	theme	post-translational	121:138	arg1	modification					140:151	a complex and common post-translational modification	100:151	a complex and common post-translational modification of proteins	100:163	Glycosylation is a complex and common post-translational modification of proteins.
34132263	1	58	theme	post-translational	121:138	arg1	Glycosylation					83:95	Glycosylation	83:95	Glycosylation	83:95	Glycosylation is a complex and common post-translational modification of proteins.
34132263	2	59	from	glycans	297:303	arg1	systems					319:325	biological systems	308:325	biological systems	308:325	To study glycosylation, liquid chromatography-mass spectrometry (LC-MS) is often used to profile and structurally characterize the glycans in biological systems.
34132263	8	60	theme	permethylated	1068:1080	arg1	analysis					1089:1096	the permethylated glycan analysis	1064:1096	the permethylated glycan analysis	1064:1096	The use of 200 cm μPAC was also investigated for the permethylated glycan analysis.
32553689	9	0	from	expression	1454:1463	arg1	lymphocytes					1508:1518	mouse splenic B lymphocytes	1492:1518	mouse splenic B lymphocytes	1492:1518	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	6	1	theme	induction	1090:1098	arg1	stage					1074:1078	the first stage	1064:1078	the first stage of cancer induction	1064:1098	The abundance of some glycans was altered during the first stage of cancer induction.
32553689	2	2	theme	background	321:330	arg1	influence					300:308	the influence	296:308	the influence of genetic background, environment and other interfering factors during cancer development	296:399	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	9	3	theme	first	1432:1436	arg1	this					1420:1423	this	1420:1423	this	1420:1423	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	9	3	theme	first	1432:1436	arg1	report					1438:1443	the first report	1428:1443	the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific	1428:1636	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	5	4	dep	RESULTS	836:842	arg1	abundance					857:865	The relative abundance	844:865	The relative abundance of seven IgG glycans, which can be classified as monoantennary	844:928	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	3	5	theme	development	558:568	arg1	stages					544:549	four stages	539:549	four stages of CRC development	539:568	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	9	6	theme	glycosyltransferases	1468:1487	arg1	consistent					1523:1532	consistent	1523:1532	consistent	1523:1532	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	9	6	theme	glycosyltransferases	1468:1487	arg1	expression					1454:1463	the expression	1450:1463	the expression of glycosyltransferases in mouse splenic B lymphocytes	1450:1518	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	10	7	theme	glycans	1815:1821	arg1	function					1803:1810	function	1803:1810	function	1803:1810	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	10	7	theme	glycans	1815:1821	arg1	structure					1789:1797	structure	1789:1797	structure	1789:1797	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	3	8	theme	Serum	497:501	arg1	N-glycans					507:515	METHODS Serum IgG N-glycans	489:515	METHODS Serum IgG N-glycans	489:515	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	9	9	theme	mouse	1492:1496	arg1	lymphocytes					1508:1518	mouse splenic B lymphocytes	1492:1518	mouse splenic B lymphocytes	1492:1518	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	10	10	theme	novel	1672:1676	arg1	approach					1678:1685	a novel approach	1670:1685	a novel approach to identify the IgG glycans related to the development of CRC	1670:1747	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	5	11	theme	relative	848:855	arg1	abundance					857:865	The relative abundance	844:865	The relative abundance of seven IgG glycans, which can be classified as monoantennary	844:928	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	5	12	theme	glycans	880:886	arg1	abundance					857:865	The relative abundance	844:865	The relative abundance of seven IgG glycans, which can be classified as monoantennary	844:928	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	8	13	theme	comprehensive	1308:1320	arg1	analysis					1322:1329	the comprehensive analysis	1304:1329	the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC	1304:1399	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	10	14	theme	GENERAL	1639:1645	arg1	SIGNIFICANCE					1647:1658	GENERAL SIGNIFICANCE	1639:1658	GENERAL SIGNIFICANCE	1639:1658	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	1	15	gly	glycosylation	144:156	arg1	IgG					167:169	serum IgG	161:169	serum IgG	161:169	BACKGROUND Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC).
32553689	3	16	theme	ultra-performance	573:589	arg1	chromatography					598:611	ultra-performance liquid chromatography	573:611	ultra-performance liquid chromatography	573:611	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	4	17	theme	glycosyltransferases	745:764	arg1	expression					723:732	the expression	719:732	the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time	719:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	3	18	theme	colitis-related	626:640	arg1	model					652:656	a typical colitis-related CRC mouse model	616:656	a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate	616:703	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	5	19	theme	sialic	944:949	arg1	acid					951:954	sialic acid	944:954	sialic acid	944:954	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	5	19	theme	sialic	944:949	arg1	RESULTS					836:842	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting,	836:980	RESULTS	836:842	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	8	20	theme	glycosylation	1338:1350	arg1	analysis					1322:1329	the comprehensive analysis	1304:1329	the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC	1304:1399	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	4	21	from	time	812:815	arg1	lymphocytes					779:789	splenic B lymphocytes	769:789	splenic B lymphocytes at the corresponding time	769:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	4	21	from	time	812:815	arg1	expression					723:732	the expression	719:732	the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time	719:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	1	22	theme	IgG	167:169	arg1	glycosylation					144:156	BACKGROUND Alternative glycosylation	121:156	BACKGROUND Alternative glycosylation of serum IgG	121:169	BACKGROUND Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC).
32553689	10	23	theme	CRC	1745:1747	arg1	development					1730:1740	the development	1726:1740	the development of CRC	1726:1747	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	0	24	theme	colon	92:96	arg1	Cancer					98:103	colitis-associated colon Cancer	73:103	colitis-associated colon Cancer	73:103	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	9	25	theme	IgG	1574:1576	arg1	N-glycans					1578:1586	IgG N-glycans	1574:1586	IgG N-glycans	1574:1586	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	1	26	theme	Alternative	132:142	arg1	glycosylation					144:156	BACKGROUND Alternative glycosylation	121:156	BACKGROUND Alternative glycosylation of serum IgG	121:169	BACKGROUND Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC).
32553689	0	27	from	profiles	42:49	arg1	development					58:68	the development	54:68	the development of colitis-associated colon Cancer in mouse model	54:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	9	28	with	consistent	1523:1532	arg1	alterations					1559:1569	the alterations	1555:1569	the alterations of IgG N-glycans	1555:1586	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	8	29	theme	colitis-associated	1378:1395	arg1	CRC					1397:1399	colitis-associated CRC	1378:1399	colitis-associated CRC	1378:1399	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	7	30	theme	cancer	1207:1212	arg1	groups					1214:1219	cancer groups	1207:1219	cancer groups	1207:1219	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	0	31	theme	N-glycan	33:40	arg1	profiles					42:49	serum IgG N-glycan profiles	23:49	serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model	23:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	8	32	dep	CONCLUSIONS	1270:1280	arg1	represents					1293:1302	represents	1293:1302	represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC	1293:1399	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	7	33	from	tissues	1196:1202	arg1	groups					1214:1219	cancer groups	1207:1219	cancer groups	1207:1219	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	4	34	theme	splenic	769:775	arg1	lymphocytes					779:789	splenic B lymphocytes	769:789	splenic B lymphocytes at the corresponding time	769:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	2	35	theme	interfering	355:365	arg1	factors					367:373	other interfering factors	349:373	other interfering factors	349:373	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	0	36	theme	Dynamic	0:6	arg1	alterations					8:18	Dynamic alterations	0:18	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.	0:119	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	10	37	theme	related	1715:1721	arg1	glycans					1707:1713	the IgG glycans	1699:1713	the IgG glycans related to the development of CRC	1699:1747	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	2	38	theme	IgG	466:468	arg1	glycan					470:475	IgG glycan	466:475	IgG glycan	466:475	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	10	39	theme	IgG	1703:1705	arg1	glycans					1707:1713	the IgG glycans	1699:1713	the IgG glycans related to the development of CRC	1699:1747	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	0	40	theme	IgG	29:31	arg1	profiles					42:49	serum IgG N-glycan profiles	23:49	serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model	23:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	7	41	theme	B	1168:1168	arg1	lymphocytes					1170:1180	splenic B lymphocytes	1160:1180	splenic B lymphocytes	1160:1180	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	6	42	theme	glycans	1037:1043	arg1	abundance					1019:1027	The abundance	1015:1027	The abundance of some glycans	1015:1043	The abundance of some glycans was altered during the first stage of cancer induction.
32553689	3	43	theme	mouse	646:650	arg1	model					652:656	a typical colitis-related CRC mouse model	616:656	a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate	616:703	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	2	44	theme	genetic	313:319	arg1	background					321:330	genetic background	313:330	genetic background	313:330	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	1	45	theme	colorectal	216:225	arg1	CRC					235:237	CRC	235:237	CRC	235:237	BACKGROUND Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC).
32553689	1	45	theme	colorectal	216:225	arg1	cancer					227:232	colorectal cancer	216:232	colorectal cancer (CRC)	216:238	BACKGROUND Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC).
32553689	5	46	theme	tumor	1001:1005	arg1	growth					1007:1012	tumor growth	1001:1012	tumor growth	1001:1012	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	3	47	theme	azoxymethane-dextran	669:688	arg1	sulfate					697:703	azoxymethane-dextran sodium sulfate	669:703	azoxymethane-dextran sodium sulfate	669:703	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	3	48	theme	IgG	503:505	arg1	N-glycans					507:515	METHODS Serum IgG N-glycans	489:515	METHODS Serum IgG N-glycans	489:515	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	4	49	from	expression	723:732	arg1	lymphocytes					779:789	splenic B lymphocytes	769:789	splenic B lymphocytes at the corresponding time	769:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	4	49	from	expression	723:732	arg1	time					812:815	the corresponding time	794:815	the corresponding time	794:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	3	50	theme	METHODS	489:495	arg1	N-glycans					507:515	METHODS Serum IgG N-glycans	489:515	METHODS Serum IgG N-glycans	489:515	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	6	51	theme	cancer	1083:1088	arg1	induction					1090:1098	cancer induction	1083:1098	cancer induction	1083:1098	The abundance of some glycans was altered during the first stage of cancer induction.
32553689	2	52	theme	dynamic	254:260	arg1	study					262:266	a dynamic study	252:266	a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan	252:475	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	3	53	theme	CRC	554:556	arg1	development					558:568	CRC development	554:568	CRC development	554:568	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	3	54	theme	liquid	591:596	arg1	chromatography					598:611	ultra-performance liquid chromatography	573:611	ultra-performance liquid chromatography	573:611	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	9	55	theme	splenic	1498:1504	arg1	lymphocytes					1508:1518	mouse splenic B lymphocytes	1492:1518	mouse splenic B lymphocytes	1492:1518	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	0	56	from	development	58:68	arg1	model					114:118	mouse model	108:118	mouse model	108:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	5	57	theme	core	931:934	arg1	fucose					936:941	core fucose	931:941	core fucose	931:941	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	5	57	theme	core	931:934	arg1	RESULTS					836:842	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting,	836:980	RESULTS	836:842	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	9	58	dep	report	1438:1443	arg1	consistent					1523:1532	consistent	1523:1532	consistent	1523:1532	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	9	58	dep	report	1438:1443	arg1	nonspecific					1626:1636	nonspecific	1626:1636	nonspecific	1626:1636	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	9	58	dep	report	1438:1443	arg1	expression					1454:1463	the expression	1450:1463	the expression of glycosyltransferases in mouse splenic B lymphocytes	1450:1518	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	9	58	dep	report	1438:1443	arg1	inconsistent					1537:1548	inconsistent	1537:1548	inconsistent	1537:1548	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	9	58	dep	report	1438:1443	arg1	tendency					1607:1614	the variation tendency	1593:1614	the variation tendency	1593:1614	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	3	59	theme	typical	618:624	arg1	model					652:656	a typical colitis-related CRC mouse model	616:656	a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate	616:703	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	1	60	theme	BACKGROUND	121:130	arg1	glycosylation					144:156	BACKGROUND Alternative glycosylation	121:156	BACKGROUND Alternative glycosylation of serum IgG	121:169	BACKGROUND Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC).
32553689	4	61	theme	related	737:743	arg1	glycosyltransferases					745:764	related glycosyltransferases	737:764	related glycosyltransferases	737:764	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	10	62	from	research	1777:1784	arg1	function					1803:1810	function	1803:1810	function	1803:1810	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	10	62	from	research	1777:1784	arg1	structure					1789:1797	structure	1789:1797	structure	1789:1797	GENERAL SIGNIFICANCE Providing a novel approach to identify the IgG glycans related to the development of CRC and laying a foundation for research on structure and function of glycans using mouse.
32553689	8	63	theme	IgG	1334:1336	arg1	glycosylation					1338:1350	IgG glycosylation	1334:1350	IgG glycosylation	1334:1350	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	0	64	theme	colitis-associated	73:90	arg1	Cancer					98:103	colitis-associated colon Cancer	73:103	colitis-associated colon Cancer	73:103	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	1	65	theme	serum	161:165	arg1	IgG					167:169	serum IgG	161:169	serum IgG	161:169	BACKGROUND Alternative glycosylation of serum IgG has been shown to be closely associated with colorectal cancer (CRC).
32553689	2	66	theme	glycan	470:475	arg1	characteristics					447:461	carcinogenic characteristics	434:461	carcinogenic characteristics of IgG glycan	434:475	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	0	67	from	alterations	8:18	arg1	profiles					42:49	serum IgG N-glycan profiles	23:49	serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model	23:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	0	68	theme	Cancer	98:103	arg1	development					58:68	the development	54:68	the development of colitis-associated colon Cancer in mouse model	54:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	8	69	from	analysis	1322:1329	arg1	process					1367:1373	the dynamic process	1355:1373	the dynamic process of colitis-associated CRC	1355:1399	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	7	70	from	lymphocytes	1170:1180	arg1	groups					1214:1219	cancer groups	1207:1219	cancer groups	1207:1219	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	8	71	theme	dynamic	1359:1365	arg1	process					1367:1373	the dynamic process	1355:1373	the dynamic process of colitis-associated CRC	1355:1399	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	0	72	theme	mouse	108:112	arg1	model					114:118	mouse model	108:118	mouse model	108:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	9	73	theme	N-glycans	1578:1586	arg1	alterations					1559:1569	the alterations	1555:1569	the alterations of IgG N-glycans	1555:1586	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	4	74	theme	corresponding	798:810	arg1	time					812:815	the corresponding time	794:815	the corresponding time	794:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	2	75	theme	factors	367:373	arg1	influence					300:308	the influence	296:308	the influence of genetic background, environment and other interfering factors during cancer development	296:399	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	7	76	theme	different	1186:1194	arg1	tissues					1196:1202	different tissues	1186:1202	different tissues	1186:1202	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	6	77	theme	first	1068:1072	arg1	stage					1074:1078	the first stage	1064:1078	the first stage of cancer induction	1064:1098	The abundance of some glycans was altered during the first stage of cancer induction.
32553689	8	78	theme	CRC	1397:1399	arg1	process					1367:1373	the dynamic process	1355:1373	the dynamic process of colitis-associated CRC	1355:1399	CONCLUSIONS This study represents the comprehensive analysis of IgG glycosylation in the dynamic process of colitis-associated CRC.
32553689	2	79	theme	other	349:353	arg1	factors					367:373	other interfering factors	349:373	other interfering factors	349:373	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	0	80	theme	serum	23:27	arg1	profiles					42:49	serum IgG N-glycan profiles	23:49	serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model	23:118	Dynamic alterations in serum IgG N-glycan profiles in the development of colitis-associated colon Cancer in mouse model.
32553689	9	81	theme	variation	1597:1605	arg1	nonspecific					1626:1636	nonspecific	1626:1636	nonspecific	1626:1636	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	9	81	theme	variation	1597:1605	arg1	tendency					1607:1614	the variation tendency	1593:1614	the variation tendency	1593:1614	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	4	82	theme	B	777:777	arg1	lymphocytes					779:789	splenic B lymphocytes	769:789	splenic B lymphocytes at the corresponding time	769:815	Furthermore, the expression of related glycosyltransferases in splenic B lymphocytes at the corresponding time was also assessed.
32553689	7	83	theme	splenic	1160:1166	arg1	lymphocytes					1170:1180	splenic B lymphocytes	1160:1180	splenic B lymphocytes	1160:1180	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	5	84	theme	IgG	876:878	arg1	monoantennary					916:928	monoantennary	916:928	monoantennary	916:928	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	5	84	theme	IgG	876:878	arg1	glycans					880:886	seven IgG glycans	870:886	seven IgG glycans	870:886	RESULTS The relative abundance of seven IgG glycans, which can be classified as monoantennary, core fucose, sialic acid, galactose and bisecting, was changed during tumor growth.
32553689	3	85	theme	CRC	642:644	arg1	model					652:656	a typical colitis-related CRC mouse model	616:656	a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate	616:703	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	2	86	theme	cancer	382:387	arg1	development					389:399	cancer development	382:399	cancer development	382:399	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	7	87	theme	glycosyltransferases	1136:1155	arg1	expression					1122:1131	the expression	1118:1131	the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups	1118:1219	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	2	88	theme	carcinogenic	434:445	arg1	characteristics					447:461	carcinogenic characteristics	434:461	carcinogenic characteristics of IgG glycan	434:475	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
32553689	7	89	from	expression	1122:1131	arg1	lymphocytes					1170:1180	splenic B lymphocytes	1160:1180	splenic B lymphocytes	1160:1180	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	7	89	from	expression	1122:1131	arg1	tissues					1196:1202	different tissues	1186:1202	different tissues	1186:1202	Correspondingly, the expression of glycosyltransferases in splenic B lymphocytes and different tissues in cancer groups was also decreased compared to that in controls.
32553689	3	90	theme	sodium	690:695	arg1	sulfate					697:703	azoxymethane-dextran sodium sulfate	669:703	azoxymethane-dextran sodium sulfate	669:703	METHODS Serum IgG N-glycans were characterized at four stages of CRC development by ultra-performance liquid chromatography in a typical colitis-related CRC mouse model induced by azoxymethane-dextran sodium sulfate.
32553689	9	91	theme	B	1506:1506	arg1	lymphocytes					1508:1518	mouse splenic B lymphocytes	1492:1518	mouse splenic B lymphocytes	1492:1518	To our knowledge, this is the first report that the expression of glycosyltransferases in mouse splenic B lymphocytes is consistent or inconsistent with the alterations of IgG N-glycans, and the variation tendency is tissue nonspecific.
32553689	2	92	theme	environment	333:343	arg1	influence					300:308	the influence	296:308	the influence of genetic background, environment and other interfering factors during cancer development	296:399	Currently, a dynamic study which can not only minimize the influence of genetic background, environment and other interfering factors during cancer development, but also focus on investigating carcinogenic characteristics of IgG glycan is lacking.
33295603	7	0	from	activity	1443:1450	arg1	additions					1576:1584	successive additions	1565:1584	successive additions	1565:1584	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	9	1	theme	mucin-type	2026:2035	arg1	O-glycosylation					2054:2068	mucin-type core 1 clustered O-glycosylation	2026:2068	mucin-type core 1 clustered O-glycosylation	2026:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	8	2	theme	IgA1	1830:1833	arg1	O-glycosylation					1835:1849	aberrant IgA1 O-glycosylation	1821:1849	aberrant IgA1 O-glycosylation	1821:1849	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	7	3	theme	clustered	1609:1617	arg1	O-glycans					1619:1627	clustered O-glycans	1609:1627	clustered O-glycans	1609:1627	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	8	4	theme	nephropathy	1770:1780	arg1	pathogenesis					1750:1761	the pathogenesis	1746:1761	the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation	1746:1849	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	2	5	theme	cellular	307:314	arg1	differentiation					354:368	differentiation	354:368	differentiation	354:368	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	2	5	theme	cellular	307:314	arg1	signaling					340:348	signaling	340:348	signaling	340:348	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	2	5	theme	cellular	307:314	arg1	processes					329:337	cellular biosynthetic processes	307:337	cellular biosynthetic processes	307:337	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	5	6	theme	nano-liquid	840:850	arg1	LC					868:869	LC	868:869	LC	868:869	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	5	6	theme	nano-liquid	840:850	arg1	chromatography					852:865	nano-liquid chromatography	840:865	nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	840:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	5	7	from	IgA1	1030:1033	arg1	biosynthesis					991:1002	the biosynthesis	987:1002	the biosynthesis of clustered O-glycans on IgA1	987:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	1	8	theme	Golgi	201:205	arg1	apparatus					207:215	the Golgi apparatus	197:215	the Golgi apparatus	197:215	Mucin-type O-glycosylation occurs on many proteins that transit the Golgi apparatus.
33295603	5	9	theme	analyses	895:902	arg1	series					830:835	a series	828:835	a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	828:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	7	10	theme	polypeptide	1313:1323	arg1	N-acetylgalactosaminyltrasnfersase					1325:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase	1279:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1279:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	10	theme	polypeptide	1313:1323	arg1	2.4.1.41					1373:1380	GalNAc-T EC 2.4.1.41	1361:1380	GalNAc-T EC 2.4.1.41	1361:1380	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	4	11	theme	dense	716:720	arg1	clusters					722:729	dense clusters	716:729	dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1)	716:807	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	5	12	theme	chromatography	852:865	arg1	MS					891:892	MS	891:892	MS	891:892	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	5	12	theme	chromatography	852:865	arg1	spectrometry					877:888	nano-liquid chromatography (LC)-mass spectrometry	840:888	nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	840:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	5	13	theme	spectrometry	877:888	arg1	analyses					895:902	nano-liquid chromatography (LC)-mass spectrometry (MS) analyses	840:902	nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	840:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	9	14	theme	broader	1857:1863	arg1	sense					1865:1869	a broader sense	1855:1869	a broader sense	1855:1869	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	5	15	theme	glycosyltransferase	934:952	arg1	activities					964:973	glycosyltransferase enzymatic activities	934:973	glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	934:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	5	16	theme	activities	964:973	arg1	range					925:929	the range	921:929	the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	921:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	4	17	theme	proteins	752:759	arg1	regions					741:747	repeat regions	734:747	repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1)	734:807	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	4	18	theme	mucin-type	655:664	arg1	O-glycosylation					666:680	mucin-type O-glycosylation	655:680	mucin-type O-glycosylation	655:680	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	2	19	theme	proteins	270:277	arg1	function					253:260	function	253:260	function	253:260	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	2	19	theme	proteins	270:277	arg1	structure					239:247	structure	239:247	structure	239:247	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	6	20	theme	nano-LC-MS	1049:1058	arg1	quantitation					1069:1080	nano-LC-MS relative quantitation	1049:1080	nano-LC-MS relative quantitation of in vitro reaction products	1049:1110	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	7	21	dep	developed	1208:1216	arg1	determine					1232:1240	determine	1232:1240	to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1229:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	21	dep	developed	1208:1216	arg1	demonstrated					1387:1398	demonstrated	1387:1398	demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans	1387:1627	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	3	22	gly	glycoproteins	464:476	arg1	glycoproteins					464:476	glycoproteins	464:476	glycoproteins	464:476	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	0	23	theme	IgA1	103:106	arg1	sites					94:98	the clustered O-glycosylation sites	64:98	the clustered O-glycosylation sites of IgA1	64:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	0	23	theme	IgA1	103:106	arg1	IgA1					103:106	IgA1	103:106	IgA1	103:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	3	24	gly	glycosylation	447:459	arg1	glycoproteins					464:476	glycoproteins	464:476	glycoproteins	464:476	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	5	25	theme	clustered	1007:1015	arg1	O-glycans					1017:1025	clustered O-glycans	1007:1025	clustered O-glycans on IgA1	1007:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	3	26	theme	technological	387:399	arg1	advances					401:408	recent technological advances	380:408	recent technological advances	380:408	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	8	27	theme	IgA1	1648:1651	arg1	context					1637:1643	the context	1633:1643	the context of IgA1	1633:1651	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	7	28	theme	pre-existing	1404:1415	arg1	glycans					1417:1423	pre-existing glycans	1404:1423	pre-existing glycans	1404:1423	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	29	theme	glycoform-specific	1242:1259	arg1	rates					1270:1274	glycoform-specific apparent rates	1242:1274	glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1242:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	9	30	theme	competing	1951:1959	arg1	functions					1961:1969	the concerted and competing functions	1933:1969	the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation	1933:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	0	31	theme	O-glycosylation	78:92	arg1	sites					94:98	the clustered O-glycosylation sites	64:98	the clustered O-glycosylation sites of IgA1	64:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	0	31	theme	O-glycosylation	78:92	arg1	IgA1					103:106	IgA1	103:106	IgA1	103:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	0	32	theme	Quantitative	0:11	arg1	assessment					13:22	Quantitative assessment	0:22	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.	0:131	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	9	33	theme	concerted	1937:1945	arg1	functions					1961:1969	the concerted and competing functions	1933:1969	the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation	1933:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	3	34	theme	biosynthesis	519:530	arg1	understanding					498:510	the understanding	494:510	the understanding of the biosynthesis of these glycan structures	494:557	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	6	35	theme	reaction	1094:1101	arg1	products					1103:1110	in vitro reaction products	1085:1110	in vitro reaction products	1085:1110	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	3	36	theme	glycoproteins	464:476	arg1	glycosylation					447:459	profile glycosylation	439:459	profile glycosylation of glycoproteins	439:476	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	0	37	theme	clustered	68:76	arg1	sites					94:98	the clustered O-glycosylation sites	64:98	the clustered O-glycosylation sites of IgA1	64:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	0	37	theme	clustered	68:76	arg1	IgA1					103:106	IgA1	103:106	IgA1	103:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	0	38	theme	carbohydrate	38:49	arg1	additions					51:59	successive carbohydrate additions	27:59	successive carbohydrate additions to the clustered O-glycosylation sites of IgA1	27:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	9	39	from	applicable	1904:1913	arg1	sense					1865:1869	a broader sense	1855:1869	a broader sense	1855:1869	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	6	40	theme	in	1085:1086	arg1	products					1103:1110	in vitro reaction products	1085:1110	in vitro reaction products	1085:1110	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	7	41	theme	UDP-N-acetylgalactosamine	1287:1311	arg1	N-acetylgalactosaminyltrasnfersase					1325:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase	1279:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1279:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	41	theme	UDP-N-acetylgalactosamine	1287:1311	arg1	2.4.1.41					1373:1380	GalNAc-T EC 2.4.1.41	1361:1380	GalNAc-T EC 2.4.1.41	1361:1380	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	3	42	theme	structures	548:557	arg1	biosynthesis					519:530	the biosynthesis	515:530	the biosynthesis of these glycan structures	515:557	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	6	43	theme	clustered	1174:1182	arg1	O-glycans					1189:1197	clustered IgA1 O-glycans	1174:1197	clustered IgA1 O-glycans	1174:1197	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	9	44	theme	glycosyltransferases	1980:1999	arg1	functions					1961:1969	the concerted and competing functions	1933:1969	the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation	1933:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	5	45	from	biosynthesis	991:1002	arg1	IgA1					1030:1033	IgA1	1030:1033	IgA1	1030:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	7	46	theme	EC	1370:1371	arg1	N-acetylgalactosaminyltrasnfersase					1325:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase	1279:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1279:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	46	theme	EC	1370:1371	arg1	2.4.1.41					1373:1380	GalNAc-T EC 2.4.1.41	1361:1380	GalNAc-T EC 2.4.1.41	1361:1380	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	4	47	theme	O-glycosylation	666:680	arg1	process					644:650	the biosynthetic process	627:650	the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1)	627:807	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	8	48	theme	autoimmune	1786:1795	arg1	disease					1803:1809	an autoimmune renal disease	1783:1809	an autoimmune renal disease involving aberrant IgA1 O-glycosylation	1783:1849	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	8	48	theme	autoimmune	1786:1795	arg1	nephropathy					1770:1780	IgA nephropathy	1766:1780	IgA nephropathy	1766:1780	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	7	49	theme	O-glycans	1619:1627	arg1	biosynthesis					1593:1604	the biosynthesis	1589:1604	the biosynthesis of clustered O-glycans	1589:1627	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	9	50	from	sense	1865:1869	arg1	applicable					1904:1913	applicable	1904:1913	applicable	1904:1913	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	6	51	theme	unique	1133:1138	arg1	insights					1140:1147	unique insights	1133:1147	unique insights into the biosynthesis of clustered IgA1 O-glycans	1133:1197	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	9	52	theme	core	2037:2040	arg1	O-glycosylation					2054:2068	mucin-type core 1 clustered O-glycosylation	2026:2068	mucin-type core 1 clustered O-glycosylation	2026:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	4	53	theme	biosynthetic	631:642	arg1	process					644:650	the biosynthetic process	627:650	the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1)	627:807	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	2	54	theme	biosynthetic	316:327	arg1	differentiation					354:368	differentiation	354:368	differentiation	354:368	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	2	54	theme	biosynthetic	316:327	arg1	signaling					340:348	signaling	340:348	signaling	340:348	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	2	54	theme	biosynthetic	316:327	arg1	processes					329:337	cellular biosynthetic processes	307:337	cellular biosynthetic processes	307:337	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	8	55	theme	aberrant	1821:1828	arg1	O-glycosylation					1835:1849	aberrant IgA1 O-glycosylation	1821:1849	aberrant IgA1 O-glycosylation	1821:1849	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	2	56	contain	have	283:286	arg1	glycans					224:230	These glycans	218:230	These glycans	218:230	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	2	56	contain	have	283:286	arg2	roles					298:302	important roles	288:302	important roles	288:302	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	7	57	theme	successive	1565:1574	arg1	additions					1576:1584	successive additions	1565:1584	successive additions	1565:1584	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	9	58	theme	clustered	2044:2052	arg1	O-glycosylation					2054:2068	mucin-type core 1 clustered O-glycosylation	2026:2068	mucin-type core 1 clustered O-glycosylation	2026:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	8	59	theme	IgA	1766:1768	arg1	disease					1803:1809	an autoimmune renal disease	1783:1809	an autoimmune renal disease involving aberrant IgA1 O-glycosylation	1783:1849	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	8	59	theme	IgA	1766:1768	arg1	nephropathy					1770:1780	IgA nephropathy	1766:1780	IgA nephropathy	1766:1780	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	4	60	from	clusters	722:729	arg1	regions					741:747	repeat regions	734:747	repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1)	734:807	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	7	61	theme	α2,6-specific	1528:1540	arg1	sialyltransferases					1542:1559	α2,3- and α2,6-specific sialyltransferases	1518:1559	α2,3- and α2,6-specific sialyltransferases	1518:1559	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	4	62	theme	repeat	734:739	arg1	regions					741:747	repeat regions	734:747	repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1)	734:807	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	1	63	gly	O-glycosylation	144:158	arg2	proteins					175:182	many proteins	170:182	many proteins that transit the Golgi apparatus	170:215	Mucin-type O-glycosylation occurs on many proteins that transit the Golgi apparatus.
33295603	6	64	theme	O-glycans	1189:1197	arg1	biosynthesis					1158:1169	the biosynthesis	1154:1169	the biosynthesis of clustered IgA1 O-glycans	1154:1197	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	2	65	theme	many	265:268	arg1	proteins					270:277	many proteins	265:277	many proteins	265:277	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	5	66	theme	-mass	871:875	arg1	MS					891:892	MS	891:892	MS	891:892	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	5	66	theme	-mass	871:875	arg1	spectrometry					877:888	nano-liquid chromatography (LC)-mass spectrometry	840:888	nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	840:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	1	67	theme	Mucin-type	133:142	arg1	O-glycosylation					144:158	Mucin-type O-glycosylation	133:158	Mucin-type O-glycosylation	133:158	Mucin-type O-glycosylation occurs on many proteins that transit the Golgi apparatus.
33295603	7	68	theme	core	1485:1488	arg1	galactosyltransferase					1492:1512	core 1 galactosyltransferase	1485:1512	core 1 galactosyltransferase	1485:1512	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	2	69	theme	important	288:296	arg1	roles					298:302	important roles	288:302	important roles	288:302	These glycans impact structure and function of many proteins and have important roles in cellular biosynthetic processes, signaling and differentiation.
33295603	5	70	theme	enzymatic	954:962	arg1	activities					964:973	glycosyltransferase enzymatic activities	934:973	glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1	934:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	4	71	theme	mucins	774:779	arg1	IgA1					803:806	IgA1	803:806	IgA1	803:806	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	4	71	theme	mucins	774:779	arg1	A1					799:800	the mucins or immunoglobulin A1	770:800	A1	799:800	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	7	72	theme	human	1281:1285	arg1	N-acetylgalactosaminyltrasnfersase					1325:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase	1279:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1279:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	72	theme	human	1281:1285	arg1	2.4.1.41					1373:1380	GalNAc-T EC 2.4.1.41	1361:1380	GalNAc-T EC 2.4.1.41	1361:1380	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	1	73	theme	many	170:173	arg1	proteins					175:182	many proteins	170:182	many proteins that transit the Golgi apparatus	170:215	Mucin-type O-glycosylation occurs on many proteins that transit the Golgi apparatus.
33295603	6	74	theme	relative	1060:1067	arg1	quantitation					1069:1080	nano-LC-MS relative quantitation	1049:1080	nano-LC-MS relative quantitation of in vitro reaction products	1049:1110	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	3	75	theme	recent	380:385	arg1	advances					401:408	recent technological advances	380:408	recent technological advances	380:408	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	7	76	theme	glycosyltransferases	1455:1474	arg1	activity					1443:1450	subsequent activity	1432:1450	subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions	1432:1584	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	8	77	contain	have	1668:1671	arg2	potential					1673:1681	potential	1673:1681	potential	1673:1681	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	8	77	contain	have	1668:1671	arg1	results					1660:1666	these results	1654:1666	these results	1654:1666	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	7	78	theme	apparent	1261:1268	arg1	rates					1270:1274	glycoform-specific apparent rates	1242:1274	glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1242:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	79	theme	α2,3-	1518:1522	arg1	sialyltransferases					1542:1559	α2,3- and α2,6-specific sialyltransferases	1518:1559	α2,3- and α2,6-specific sialyltransferases	1518:1559	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	3	80	theme	enhanced	415:422	arg1	ability					428:434	enhanced our ability	415:434	enhanced our ability	415:434	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	0	81	gly	O-glycosylation	78:92	arg2	IgA1					103:106	IgA1	103:106	IgA1	103:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	0	81	gly	O-glycosylation	78:92	arg1	IgA1					103:106	IgA1	103:106	IgA1	103:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	0	81	gly	O-glycosylation	78:92	arg2	sites					94:98	the clustered O-glycosylation sites	64:98	the clustered O-glycosylation sites of IgA1	64:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	6	82	dep	in	1085:1086	arg1	vitro					1088:1092	vitro	1088:1092	vitro	1088:1092	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	5	83	theme	O-glycans	1017:1025	arg1	biosynthesis					991:1002	the biosynthesis	987:1002	the biosynthesis of clustered O-glycans on IgA1	987:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
33295603	7	84	theme	subsequent	1432:1441	arg1	activity					1443:1450	subsequent activity	1432:1450	subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions	1432:1584	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	3	85	theme	profile	439:445	arg1	glycosylation					447:459	profile glycosylation	439:459	profile glycosylation of glycoproteins	439:476	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	4	86	theme	immunoglobulin	784:797	arg1	IgA1					803:806	IgA1	803:806	IgA1	803:806	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	4	86	theme	immunoglobulin	784:797	arg1	A1					799:800	the mucins or immunoglobulin A1	770:800	A1	799:800	Some of these limitations stem from the difficulty to track the biosynthetic process of mucin-type O-glycosylation, especially when glycans occur in dense clusters in repeat regions of proteins, such as the mucins or immunoglobulin A1 (IgA1).
33295603	0	87	theme	successive	27:36	arg1	additions					51:59	successive carbohydrate additions	27:59	successive carbohydrate additions to the clustered O-glycosylation sites of IgA1	27:106	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	6	88	theme	products	1103:1110	arg1	quantitation					1069:1080	nano-LC-MS relative quantitation	1049:1080	nano-LC-MS relative quantitation of in vitro reaction products	1049:1110	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	0	89	theme	additions	51:59	arg1	assessment					13:22	Quantitative assessment	0:22	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.	0:131	Quantitative assessment of successive carbohydrate additions to the clustered O-glycosylation sites of IgA1 by glycosyltransferases.
33295603	9	90	theme	functions	1961:1969	arg1	studies					1922:1928	the studies	1918:1928	the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation	1918:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	6	91	theme	IgA1	1184:1187	arg1	O-glycans					1189:1197	clustered IgA1 O-glycans	1174:1197	clustered IgA1 O-glycans	1174:1197	By utilizing nano-LC-MS relative quantitation of in vitro reaction products, our results provide unique insights into the biosynthesis of clustered IgA1 O-glycans.
33295603	9	92	theme	other	1974:1978	arg1	glycosyltransferases					1980:1999	other glycosyltransferases	1974:1999	other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation	1974:2068	In a broader sense, these methods and workflows are applicable to the studies of the concerted and competing functions of other glycosyltransferases that initiate and extend mucin-type core 1 clustered O-glycosylation.
33295603	8	93	theme	molecular	1711:1719	arg1	mechanisms					1721:1730	the molecular mechanisms	1707:1730	the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation	1707:1849	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	3	94	contain	have	410:413	arg1	advances					401:408	recent technological advances	380:408	recent technological advances	380:408	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	3	94	contain	have	410:413	arg2	ability					428:434	enhanced our ability	415:434	enhanced our ability	415:434	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	7	95	theme	GalNAc-T	1361:1368	arg1	N-acetylgalactosaminyltrasnfersase					1325:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase	1279:1358	a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1279:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	7	95	theme	GalNAc-T	1361:1368	arg1	2.4.1.41					1373:1380	GalNAc-T EC 2.4.1.41	1361:1380	GalNAc-T EC 2.4.1.41	1361:1380	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	3	96	from	limitations	479:489	arg1	understanding					498:510	the understanding	494:510	the understanding of the biosynthesis of these glycan structures	494:557	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	3	97	theme	glycan	541:546	arg1	structures					548:557	these glycan structures	535:557	these glycan structures	535:557	Although recent technological advances have enhanced our ability to profile glycosylation of glycoproteins, limitations in the understanding of the biosynthesis of these glycan structures remain.
33295603	8	98	theme	renal	1797:1801	arg1	disease					1803:1809	an autoimmune renal disease	1783:1809	an autoimmune renal disease involving aberrant IgA1 O-glycosylation	1783:1849	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	8	98	theme	renal	1797:1801	arg1	nephropathy					1770:1780	IgA nephropathy	1766:1780	IgA nephropathy	1766:1780	In the context of IgA1, these results have potential to provide insight into the molecular mechanisms implicated in the pathogenesis of IgA nephropathy, an autoimmune renal disease involving aberrant IgA1 O-glycosylation.
33295603	7	99	theme	N-acetylgalactosaminyltrasnfersase	1325:1358	arg1	rates					1270:1274	glycoform-specific apparent rates	1242:1274	glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41)	1242:1381	We have developed a workflow to determine glycoform-specific apparent rates of a human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltrasnfersase (GalNAc-T EC 2.4.1.41) and demonstrated how pre-existing glycans affect subsequent activity of glycosyltransferases, such as core 1 galactosyltransferase and α2,3- and α2,6-specific sialyltransferases, in successive additions in the biosynthesis of clustered O-glycans.
33295603	5	100	from	O-glycans	1017:1025	arg1	IgA1					1030:1033	IgA1	1030:1033	IgA1	1030:1033	Here, we describe a series of nano-liquid chromatography (LC)-mass spectrometry (MS) analyses that demonstrate the range of glycosyltransferase enzymatic activities involved in the biosynthesis of clustered O-glycans on IgA1.
34780171	9	0	theme	efficient	2021:2029	arg1	ZIC-cHILIC					2004:2013	stepwise ZIC-cHILIC	1995:2013	stepwise ZIC-cHILIC	1995:2013	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	9	0	theme	efficient	2021:2029	arg1	method					2031:2036	an efficient method	2018:2036	an efficient method to explore the under-represented sialoglycoproteome	2018:2088	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	2	1	gly	glycopeptides	374:386	arg2	glycopeptides					374:386	enrich glycopeptides	367:386	enrich glycopeptides	367:386	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	3	2	with	chromatography	616:629	arg1	group					656:660	the exposed choline group	636:660	the exposed choline group (ZIC-cHILIC)	636:673	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	3	2	with	chromatography	616:629	arg1	ZIC-cHILIC					663:672	ZIC-cHILIC	663:672	ZIC-cHILIC	663:672	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	2	3	theme	labile	427:432	arg1	tools					358:362	high-performance tools	341:362	high-performance tools to enrich glycopeptides	341:386	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	3	theme	labile	427:432	arg1	sialoglycopeptides					434:451	the negatively charged and labile sialoglycopeptides	400:451	especially the negatively charged and labile sialoglycopeptides	389:451	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	7	4	theme	Byonic	1620:1625	arg1	glycoproteins					1605:1617	1118 glycoproteins	1600:1617	1118 glycoproteins (Byonic score > 100)	1600:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	4	theme	Byonic	1620:1625	arg1	>					1633:1633	Byonic score > 100	1620:1637	Byonic score > 100	1620:1637	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	6	5	theme	4.6-	1315:1318	arg1	coverage					1303:1310	superior coverage	1294:1310	good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides	1232:1395	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	6	5	theme	4.6-	1315:1318	arg1	reproducibility					1237:1251	good reproducibility	1232:1251	good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides	1232:1395	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	6	6	gly	glycopeptides	1360:1372	arg2	glycopeptides					1360:1372	glycopeptides	1360:1372	glycopeptides	1360:1372	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	6	7	theme	conventional	1409:1420	arg1	TiO2					1422:1425	conventional TiO2	1409:1425	conventional TiO2	1409:1425	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	7	8	theme	glycoproteins	1605:1617	arg1	N-glycosites					1584:1595	2434 N-glycosites	1579:1595	2434 N-glycosites of 1118 glycoproteins (Byonic score > 100)	1579:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	3	9	gly	glycopeptides	743:755	arg2	glycopeptides					743:755	intact glycopeptides	736:755	intact glycopeptides	736:755	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	3	10	from	implementation	561:574	arg1	StageTip					678:685	StageTip	678:685	StageTip for simultaneous enrichment and fractionation of intact glycopeptides	678:755	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	3	11	theme	choline	648:654	arg1	group					656:660	the exposed choline group	636:660	the exposed choline group (ZIC-cHILIC)	636:673	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	3	11	theme	choline	648:654	arg1	ZIC-cHILIC					663:672	ZIC-cHILIC	663:672	ZIC-cHILIC	663:672	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	7	12	from	N-glycosites	1584:1595	arg1	glycopeptides					1544:1556	7367 unique glycopeptides	1532:1556	7367 unique glycopeptides	1532:1556	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	12	from	N-glycosites	1584:1595	arg1	glycans					1566:1572	166 glycans	1562:1572	166 glycans	1562:1572	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	4	13	theme	cancer	786:791	arg1	cells					793:797	lung cancer cells	781:797	lung cancer cells	781:797	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	2	14	gly	glycopeptides	326:338	arg2	glycopeptides					326:338	glycopeptides	326:338	glycopeptides	326:338	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	15	theme	enrich	367:372	arg1	glycopeptides					374:386	enrich glycopeptides	367:386	enrich glycopeptides	367:386	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	4	16	gly	sialoglycopeptides	964:981	arg2	%					989:989	77-89%	984:989	77-89%	984:989	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	4	16	gly	sialoglycopeptides	964:981	arg2	sialoglycopeptides					964:981	sialoglycopeptides	964:981	sialoglycopeptides (77-89%)	964:990	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	4	17	theme	model	763:767	arg1	study					769:773	a model study	761:773	a model study using lung cancer cells	761:797	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	4	18	theme	hydrophilic	1010:1020	arg1	fractions					1022:1030	the subsequent hydrophilic fractions	995:1030	the subsequent hydrophilic fractions	995:1030	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	3	19	theme	simultaneous	691:702	arg1	enrichment					704:713	simultaneous enrichment	691:713	simultaneous enrichment	691:713	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	5	20	theme	stepwise	1037:1044	arg1	elution					1046:1052	The stepwise elution	1033:1052	The stepwise elution	1033:1052	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	2	21	theme	glycopeptides	326:338	arg1	microheterogeneity					254:271	microheterogeneity	254:271	microheterogeneity	254:271	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	21	theme	glycopeptides	326:338	arg1	stoichiometry					278:290	low stoichiometry	274:290	low stoichiometry	274:290	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	21	theme	glycopeptides	326:338	arg1	macro-					243:248	the structural macro-	228:248	the structural macro-	228:248	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	21	theme	glycopeptides	326:338	arg1	efficiency					312:321	low ionization efficiency	297:321	low ionization efficiency	297:321	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	5	22	theme	glycopeptide	1067:1078	arg1	efficiency					1094:1103	a high glycopeptide fractionation efficiency	1060:1103	a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions	1060:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	3	23	theme	glycopeptides	743:755	arg1	enrichment					704:713	simultaneous enrichment	691:713	simultaneous enrichment	691:713	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	3	23	theme	glycopeptides	743:755	arg1	fractionation					719:731	fractionation	719:731	fractionation	719:731	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	6	24	gly	sialoglycopeptides	1378:1395	arg2	sialoglycopeptides					1378:1395	sialoglycopeptides	1378:1395	sialoglycopeptides	1378:1395	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	2	25	gly	microheterogeneity	254:271	arg1	glycopeptides					326:338	glycopeptides	326:338	glycopeptides	326:338	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	26	theme	ionization	301:310	arg1	efficiency					312:321	low ionization efficiency	297:321	low ionization efficiency	297:321	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	7	27	with	result	1490:1495	arg1	sialoglycopeptides					1507:1524	2742 sialoglycopeptides	1502:1524	2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100)	1502:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	1	28	theme	glycosylation	151:163	arg1	Alterations					128:138	Alterations	128:138	Alterations of protein glycosylation	128:163	Alterations of protein glycosylation are closely related with pathophysiological regulation.
34780171	7	29	gly	glycoproteins	1605:1617	arg1	glycoproteins					1605:1617	1118 glycoproteins	1600:1617	1118 glycoproteins (Byonic score > 100)	1600:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	29	gly	glycoproteins	1605:1617	arg1	>					1633:1633	Byonic score > 100	1620:1637	Byonic score > 100	1620:1637	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	4	30	theme	high	905:908	arg1	specificity					921:931	high enrichment specificity	905:931	high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%)	905:990	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	9	31	theme	demonstrated	1919:1930	arg1	specificity					1948:1958	The demonstrated high enrichment specificity	1915:1958	The demonstrated high enrichment specificity	1915:1958	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	0	32	theme	Large-Scale	92:102	arg1	N-Sialoglycoproteomics					104:125	Large-Scale N-Sialoglycoproteomics	92:125	Large-Scale N-Sialoglycoproteomics	92:125	ZIC-cHILIC-Based StageTip for Simultaneous Glycopeptide Enrichment and Fractionation toward Large-Scale N-Sialoglycoproteomics.
34780171	4	33	theme	acetonitrile	838:849	arg1	percentage					824:833	a high percentage	817:833	a high percentage of acetonitrile	817:849	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	0	34	theme	ZIC-cHILIC-Based	0:15	arg1	StageTip					17:24	ZIC-cHILIC-Based StageTip	0:24	ZIC-cHILIC-Based StageTip for Simultaneous Glycopeptide Enrichment	0:65	ZIC-cHILIC-Based StageTip for Simultaneous Glycopeptide Enrichment and Fractionation toward Large-Scale N-Sialoglycoproteomics.
34780171	5	35	theme	high	1062:1065	arg1	efficiency					1094:1103	a high glycopeptide fractionation efficiency	1060:1103	a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions	1060:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	6	36	theme	ZIC-cHILIC	1190:1199	arg1	strategy					1210:1217	the ZIC-cHILIC stepwise strategy	1186:1217	the ZIC-cHILIC stepwise strategy	1186:1217	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	9	37	theme	enrichment	1937:1946	arg1	specificity					1948:1958	The demonstrated high enrichment specificity	1915:1958	The demonstrated high enrichment specificity	1915:1958	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	2	38	theme	underexplored	505:517	arg1	glycoproteome					519:531	the underexplored glycoproteome	501:531	the underexplored glycoproteome	501:531	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	3	39	theme	exposed	640:646	arg1	group					656:660	the exposed choline group	636:660	the exposed choline group (ZIC-cHILIC)	636:673	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	3	39	theme	exposed	640:646	arg1	ZIC-cHILIC					663:672	ZIC-cHILIC	663:672	ZIC-cHILIC	663:672	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	7	40	theme	deepest	1660:1666	arg1	profiles					1683:1690	the deepest glycoproteomic profiles	1656:1690	the deepest glycoproteomic profiles in single-cell type	1656:1710	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	5	41	theme	fractionation	1080:1092	arg1	efficiency					1094:1103	a high glycopeptide fractionation efficiency	1060:1103	a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions	1060:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	2	42	theme	structural	232:241	arg1	macro-					243:248	the structural macro-	228:248	the structural macro-	228:248	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	6	43	dep	reproducibility	1237:1251	arg1	%					1257:1257	>80%	1254:1257	>80%	1254:1257	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	0	44	theme	Glycopeptide	43:54	arg1	Enrichment					56:65	Simultaneous Glycopeptide Enrichment	30:65	Simultaneous Glycopeptide Enrichment	30:65	ZIC-cHILIC-Based StageTip for Simultaneous Glycopeptide Enrichment and Fractionation toward Large-Scale N-Sialoglycoproteomics.
34780171	5	45	theme	adjacent	1148:1155	arg1	fractions					1157:1165	adjacent fractions	1148:1165	adjacent fractions	1148:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	5	46	gly	glycopeptides	1126:1138	arg2	glycopeptides					1126:1138	glycopeptides	1126:1138	glycopeptides between adjacent fractions	1126:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	6	47	from	%	1257:1257	arg1	analysis					1273:1280	triplicate analysis	1262:1280	triplicate analysis	1262:1280	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	3	48	theme	zwitterionic	579:590	arg1	chromatography					616:629	zwitterionic hydrophilic interaction chromatography	579:629	zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC)	579:673	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	4	49	gly	glycopeptides	937:949	arg2	%					957:957	92-96%	952:957	92-96%	952:957	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	4	49	gly	glycopeptides	937:949	arg2	glycopeptides					937:949	glycopeptides	937:949	glycopeptides (92-96%)	937:958	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	6	50	theme	triplicate	1262:1271	arg1	analysis					1273:1280	triplicate analysis	1262:1280	triplicate analysis	1262:1280	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	7	51	theme	glycoproteomic	1668:1681	arg1	profiles					1683:1690	the deepest glycoproteomic profiles	1656:1690	the deepest glycoproteomic profiles in single-cell type	1656:1710	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	8	52	theme	site-specific	1801:1813	arg1	glycosylation					1815:1827	site-specific glycosylation	1801:1827	site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R	1801:1912	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	7	53	gly	glycopeptides	1544:1556	arg1	N-glycosites					1584:1595	2434 N-glycosites	1579:1595	2434 N-glycosites of 1118 glycoproteins (Byonic score > 100)	1579:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	53	gly	glycopeptides	1544:1556	arg2	glycopeptides					1544:1556	7367 unique glycopeptides	1532:1556	7367 unique glycopeptides	1532:1556	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	54	theme	score	1627:1631	arg1	glycoproteins					1605:1617	1118 glycoproteins	1600:1617	1118 glycoproteins (Byonic score > 100)	1600:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	54	theme	score	1627:1631	arg1	>					1633:1633	Byonic score > 100	1620:1637	Byonic score > 100	1620:1637	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	5	55	theme	glycopeptides	1126:1138	arg1	%					1113:1113	a <10% overlap	1108:1121	a <10% overlap of glycopeptides between adjacent fractions	1108:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	5	55	theme	glycopeptides	1126:1138	arg1	glycopeptides					1126:1138	glycopeptides	1126:1138	glycopeptides between adjacent fractions	1126:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	3	56	theme	interaction	604:614	arg1	chromatography					616:629	zwitterionic hydrophilic interaction chromatography	579:629	zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC)	579:673	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	8	57	theme	druggable	1837:1845	arg1	ERBB2					1885:1889	ERBB2	1885:1889	ERBB2	1885:1889	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	57	theme	druggable	1837:1845	arg1	IGF1R					1908:1912	IGF1R	1908:1912	IGF1R	1908:1912	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	57	theme	druggable	1837:1845	arg1	EGFR					1874:1877	EGFR	1874:1877	EGFR	1874:1877	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	57	theme	druggable	1837:1845	arg1	ERBB3					1892:1896	ERBB3	1892:1896	ERBB3	1892:1896	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	57	theme	druggable	1837:1845	arg1	AXL					1899:1901	AXL	1899:1901	AXL	1899:1901	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	57	theme	druggable	1837:1845	arg1	proteins					1856:1863	many druggable receptor proteins	1832:1863	many druggable receptor proteins	1832:1863	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	57	theme	druggable	1837:1845	arg1	MET					1880:1882	MET	1880:1882	MET	1880:1882	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	58	gly	glycosylation	1815:1827	arg1	ERBB2					1885:1889	ERBB2	1885:1889	ERBB2	1885:1889	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	58	gly	glycosylation	1815:1827	arg1	IGF1R					1908:1912	IGF1R	1908:1912	IGF1R	1908:1912	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	58	gly	glycosylation	1815:1827	arg1	EGFR					1874:1877	EGFR	1874:1877	EGFR	1874:1877	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	58	gly	glycosylation	1815:1827	arg1	ERBB3					1892:1896	ERBB3	1892:1896	ERBB3	1892:1896	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	58	gly	glycosylation	1815:1827	arg1	AXL					1899:1901	AXL	1899:1901	AXL	1899:1901	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	58	gly	glycosylation	1815:1827	arg1	proteins					1856:1863	many druggable receptor proteins	1832:1863	many druggable receptor proteins	1832:1863	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	58	gly	glycosylation	1815:1827	arg1	MET					1880:1882	MET	1880:1882	MET	1880:1882	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	6	59	theme	good	1232:1235	arg1	reproducibility					1237:1251	good reproducibility	1232:1251	good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides	1232:1395	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	8	60	theme	glycoproteomic	1767:1780	arg1	atlas					1782:1786	the large-scale glycoproteomic atlas	1751:1786	the large-scale glycoproteomic atlas	1751:1786	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	61	theme	proteins	1856:1863	arg1	glycosylation					1815:1827	site-specific glycosylation	1801:1827	site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R	1801:1912	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	7	62	theme	1118	1600:1603	arg1	glycoproteins					1605:1617	1118 glycoproteins	1600:1617	1118 glycoproteins (Byonic score > 100)	1600:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	62	theme	1118	1600:1603	arg1	>					1633:1633	Byonic score > 100	1620:1637	Byonic score > 100	1620:1637	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	2	63	theme	high-performance	341:356	arg1	tools					358:362	high-performance tools	341:362	high-performance tools to enrich glycopeptides	341:386	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	63	theme	high-performance	341:356	arg1	sialoglycopeptides					434:451	the negatively charged and labile sialoglycopeptides	400:451	especially the negatively charged and labile sialoglycopeptides	389:451	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	6	64	theme	superior	1294:1301	arg1	coverage					1303:1310	superior coverage	1294:1310	good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides	1232:1395	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	9	65	theme	under-represented	2053:2069	arg1	sialoglycoproteome					2071:2088	the under-represented sialoglycoproteome	2049:2088	the under-represented sialoglycoproteome	2049:2088	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	4	66	theme	lung	781:784	arg1	cells					793:797	lung cancer cells	781:797	lung cancer cells	781:797	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	7	67	theme	unique	1537:1542	arg1	glycopeptides					1544:1556	7367 unique glycopeptides	1532:1556	7367 unique glycopeptides	1532:1556	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	2	68	theme	charged	415:421	arg1	tools					358:362	high-performance tools	341:362	high-performance tools to enrich glycopeptides	341:386	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	68	theme	charged	415:421	arg1	sialoglycopeptides					434:451	the negatively charged and labile sialoglycopeptides	400:451	especially the negatively charged and labile sialoglycopeptides	389:451	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	69	theme	low	297:299	arg1	efficiency					312:321	low ionization efficiency	297:321	low ionization efficiency	297:321	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	7	70	gly	sialoglycopeptides	1507:1524	arg2	sialoglycopeptides					1507:1524	2742 sialoglycopeptides	1502:1524	2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100)	1502:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	6	71	theme	more	1355:1358	arg1	glycopeptides					1360:1372	glycopeptides	1360:1372	glycopeptides	1360:1372	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	4	72	theme	subsequent	999:1008	arg1	fractions					1022:1030	the subsequent hydrophilic fractions	995:1030	the subsequent hydrophilic fractions	995:1030	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	3	73	theme	intact	736:741	arg1	glycopeptides					743:755	intact glycopeptides	736:755	intact glycopeptides	736:755	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	4	74	theme	high	819:822	arg1	percentage					824:833	a high percentage	817:833	a high percentage of acetonitrile	817:849	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	4	75	gly	nonglycopeptides	874:889	arg2	nonglycopeptides					874:889	nonglycopeptides	874:889	nonglycopeptides	874:889	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	1	76	theme	pathophysiological	190:207	arg1	regulation					209:218	pathophysiological regulation	190:218	pathophysiological regulation	190:218	Alterations of protein glycosylation are closely related with pathophysiological regulation.
34780171	7	77	theme	single-cell	1695:1705	arg1	type					1707:1710	single-cell type	1695:1710	single-cell type	1695:1710	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	4	78	theme	early	800:804	arg1	elution					806:812	early elution	800:812	early elution by a high percentage of acetonitrile	800:849	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	7	79	theme	profiles	1683:1690	arg1	profiles					1683:1690	the deepest glycoproteomic profiles	1656:1690	the deepest glycoproteomic profiles in single-cell type	1656:1710	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	79	theme	profiles	1683:1690	arg1	one					1649:1651	one	1649:1651	one	1649:1651	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	5	80	gly	glycopeptide	1067:1078	arg2	glycopeptide					1067:1078	a high glycopeptide fractionation efficiency	1060:1103	a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions	1060:1165	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	7	81	gly	N-glycosites	1584:1595	arg2	N-glycosites					1584:1595	2434 N-glycosites	1579:1595	2434 N-glycosites of 1118 glycoproteins (Byonic score > 100)	1579:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	81	gly	N-glycosites	1584:1595	arg1	glycoproteins					1605:1617	1118 glycoproteins	1600:1617	1118 glycoproteins (Byonic score > 100)	1600:1638	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	7	81	gly	N-glycosites	1584:1595	arg1	>					1633:1633	Byonic score > 100	1620:1637	Byonic score > 100	1620:1637	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	6	82	theme	stepwise	1201:1208	arg1	strategy					1210:1217	the ZIC-cHILIC stepwise strategy	1186:1217	the ZIC-cHILIC stepwise strategy	1186:1217	Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively.
34780171	9	83	theme	high	1932:1935	arg1	specificity					1948:1958	The demonstrated high enrichment specificity	1915:1958	The demonstrated high enrichment specificity	1915:1958	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	0	84	theme	Simultaneous	30:41	arg1	Enrichment					56:65	Simultaneous Glycopeptide Enrichment	30:65	Simultaneous Glycopeptide Enrichment	30:65	ZIC-cHILIC-Based StageTip for Simultaneous Glycopeptide Enrichment and Fractionation toward Large-Scale N-Sialoglycoproteomics.
34780171	7	85	from	profiles	1683:1690	arg1	type					1707:1710	single-cell type	1695:1710	single-cell type	1695:1710	To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type.
34780171	1	86	theme	protein	143:149	arg1	glycosylation					151:163	protein glycosylation	143:163	protein glycosylation	143:163	Alterations of protein glycosylation are closely related with pathophysiological regulation.
34780171	2	87	theme	glycoproteome	519:531	arg1	identification					483:496	the identification	479:496	the identification of the underexplored glycoproteome	479:531	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	3	88	theme	first	555:559	arg1	implementation					561:574	the first implementation	551:574	the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides	551:755	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	5	89	dep	%	1113:1113	arg1	overlap					1115:1121	overlap	1115:1121	overlap	1115:1121	The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions.
34780171	9	90	theme	identification	1964:1977	arg1	depth					1979:1983	identification depth	1964:1983	identification depth	1964:1983	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	2	91	gly	sialoglycopeptides	434:451	arg2	sialoglycopeptides					434:451	the negatively charged and labile sialoglycopeptides	400:451	especially the negatively charged and labile sialoglycopeptides	389:451	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	2	91	gly	sialoglycopeptides	434:451	arg2	tools					358:362	high-performance tools	341:362	high-performance tools to enrich glycopeptides	341:386	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	8	92	theme	immunoprecipitation	1725:1743	arg1	step					1745:1748	the immunoprecipitation step	1721:1748	the immunoprecipitation step	1721:1748	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	2	93	theme	low	274:276	arg1	stoichiometry					278:290	low stoichiometry	274:290	low stoichiometry	274:290	Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome.
34780171	3	94	theme	chromatography	616:629	arg1	implementation					561:574	the first implementation	551:574	the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides	551:755	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	3	95	theme	hydrophilic	592:602	arg1	chromatography					616:629	zwitterionic hydrophilic interaction chromatography	579:629	zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC)	579:673	Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides.
34780171	9	96	theme	stepwise	1995:2002	arg1	ZIC-cHILIC					2004:2013	stepwise ZIC-cHILIC	1995:2013	stepwise ZIC-cHILIC	1995:2013	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	9	96	theme	stepwise	1995:2002	arg1	method					2031:2036	an efficient method	2018:2036	an efficient method to explore the under-represented sialoglycoproteome	2018:2088	The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.
34780171	4	97	theme	enrichment	910:919	arg1	specificity					921:931	high enrichment specificity	905:931	high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%)	905:990	In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions.
34780171	8	98	theme	many	1832:1835	arg1	ERBB2					1885:1889	ERBB2	1885:1889	ERBB2	1885:1889	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	98	theme	many	1832:1835	arg1	IGF1R					1908:1912	IGF1R	1908:1912	IGF1R	1908:1912	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	98	theme	many	1832:1835	arg1	EGFR					1874:1877	EGFR	1874:1877	EGFR	1874:1877	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	98	theme	many	1832:1835	arg1	ERBB3					1892:1896	ERBB3	1892:1896	ERBB3	1892:1896	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	98	theme	many	1832:1835	arg1	AXL					1899:1901	AXL	1899:1901	AXL	1899:1901	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	98	theme	many	1832:1835	arg1	proteins					1856:1863	many druggable receptor proteins	1832:1863	many druggable receptor proteins	1832:1863	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	98	theme	many	1832:1835	arg1	MET					1880:1882	MET	1880:1882	MET	1880:1882	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	99	theme	large-scale	1755:1765	arg1	atlas					1782:1786	the large-scale glycoproteomic atlas	1751:1786	the large-scale glycoproteomic atlas	1751:1786	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	100	theme	receptor	1847:1854	arg1	ERBB2					1885:1889	ERBB2	1885:1889	ERBB2	1885:1889	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	100	theme	receptor	1847:1854	arg1	IGF1R					1908:1912	IGF1R	1908:1912	IGF1R	1908:1912	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	100	theme	receptor	1847:1854	arg1	EGFR					1874:1877	EGFR	1874:1877	EGFR	1874:1877	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	100	theme	receptor	1847:1854	arg1	ERBB3					1892:1896	ERBB3	1892:1896	ERBB3	1892:1896	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	100	theme	receptor	1847:1854	arg1	AXL					1899:1901	AXL	1899:1901	AXL	1899:1901	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	100	theme	receptor	1847:1854	arg1	proteins					1856:1863	many druggable receptor proteins	1832:1863	many druggable receptor proteins	1832:1863	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
34780171	8	100	theme	receptor	1847:1854	arg1	MET					1880:1882	MET	1880:1882	MET	1880:1882	Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R.
32097449	7	0	theme	glycosylation	1238:1250	arg1	pathways					1252:1259	divergent glycosylation pathways	1228:1259	divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors	1228:1322	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	7	1	theme	glycan	1134:1139	arg1	studies					1149:1155	glycan binding studies	1134:1155	glycan binding studies	1134:1155	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	6	2	theme	standard	979:986	arg1	chemotherapeutics					988:1004	standard chemotherapeutics	979:1004	standard chemotherapeutics	979:1004	Remarkably, ML6 displays antitumor activity that is >105 times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells.
32097449	5	3	theme	root	767:770	arg1	transcriptome					772:784	a tropical rainforest tree root transcriptome	740:784	a tropical rainforest tree root transcriptome	740:784	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	4	4	theme	lectin	542:547	arg1	discovery					505:513	the discovery	501:513	the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death	501:679	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	7	5	theme	binding	1141:1147	arg1	studies					1149:1155	glycan binding studies	1134:1155	glycan binding studies	1134:1155	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	0	6	from	transcriptomes	57:70	arg1	Discovery					0:8	Discovery	0:8	Discovery of antitumor lectins from rainforest tree root transcriptomes.	0:71	Discovery of antitumor lectins from rainforest tree root transcriptomes.
32097449	9	7	from	resistance	1757:1766	arg1	cancer					1771:1776	cancer	1771:1776	cancer	1771:1776	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	5	8	theme	tropical	742:749	arg1	transcriptome					772:784	a tropical rainforest tree root transcriptome	740:784	a tropical rainforest tree root transcriptome	740:784	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	4	9	theme	mannose-binding	526:540	arg1	ML6					550:552	ML6	550:552	ML6	550:552	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	4	9	theme	mannose-binding	526:540	arg1	lectin					542:547	a novel mannose-binding lectin	518:547	a novel mannose-binding lectin	518:547	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	9	10	theme	competing	1629:1637	arg1	microorganisms					1639:1652	competing microorganisms	1629:1652	competing microorganisms	1629:1652	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	6	11	dep	non-transformed	1054:1068	arg1	healthy					1071:1077	healthy	1071:1077	healthy	1071:1077	Remarkably, ML6 displays antitumor activity that is >105 times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells.
32097449	9	12	theme	changing	1608:1615	arg1	defenses					1617:1624	the changing defenses	1604:1624	the changing defenses of competing microorganisms	1604:1652	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	4	13	theme	tumor-specific	613:626	arg1	glycans					628:634	these irregular tumor-specific glycans	597:634	these irregular tumor-specific glycans	597:634	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	5	14	theme	rainforest	751:760	arg1	transcriptome					772:784	a tropical rainforest tree root transcriptome	740:784	a tropical rainforest tree root transcriptome	740:784	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	15	from	domains	838:844	arg1	unusual					793:799	unusual	793:799	unusual	793:799	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	9	16	dep	understanding	1541:1553	arg1	evolves					1566:1572	evolves	1566:1572	evolves	1566:1572	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	7	17	theme	naïve	1272:1276	arg1	glycans					1306:1312	naïve and incomplete cell surface glycans	1272:1312	naïve and incomplete cell surface glycans	1272:1312	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	4	18	theme	irregular	603:611	arg1	glycans					628:634	these irregular tumor-specific glycans	597:634	these irregular tumor-specific glycans	597:634	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	3	19	theme	synthesis	367:375	arg1	disruption					346:355	disruption	346:355	disruption of glycan synthesis	346:375	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	7	20	theme	healthy	1186:1192	arg1	cells					1208:1212	healthy and malignant cells	1186:1212	healthy and malignant cells	1186:1212	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	8	21	theme	novel	1379:1383	arg1	tools					1397:1401	novel biochemical tools	1379:1401	novel biochemical tools	1379:1401	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	21	theme	novel	1379:1383	arg1	ML6					1331:1333	ML6	1331:1333	ML6	1331:1333	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	21	theme	novel	1379:1383	arg1	lectins					1358:1364	other high-valence lectins	1339:1364	other high-valence lectins	1339:1364	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	5	22	theme	unique	871:876	arg1	sequence					889:896	a unique amino acid sequence	869:896	a unique amino acid sequence	869:896	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	3	23	dep	surprisingly	332:343	arg1	Not					328:330	Not	328:330	Not	328:330	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	8	24	theme	other	1339:1343	arg1	tools					1397:1401	novel biochemical tools	1379:1401	novel biochemical tools	1379:1401	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	24	theme	other	1339:1343	arg1	ML6					1331:1333	ML6	1331:1333	ML6	1331:1333	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	24	theme	other	1339:1343	arg1	lectins					1358:1364	other high-valence lectins	1339:1364	other high-valence lectins	1339:1364	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	7	25	theme	malignant	1198:1206	arg1	cells					1208:1212	healthy and malignant cells	1186:1212	healthy and malignant cells	1186:1212	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	5	26	theme	tree	762:765	arg1	transcriptome					772:784	a tropical rainforest tree root transcriptome	740:784	a tropical rainforest tree root transcriptome	740:784	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	27	theme	mannose	822:828	arg1	QxDxNxVxY					847:855	QxDxNxVxY	847:855	QxDxNxVxY	847:855	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	27	theme	mannose	822:828	arg1	each					859:862	each	859:862	each	859:862	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	27	theme	mannose	822:828	arg1	domains					838:844	six canonical mannose binding domains	808:844	six canonical mannose binding domains (QxDxNxVxY)	808:856	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	9	28	theme	combinatorial	1712:1724	arg1	therapies					1726:1734	combinatorial therapies	1712:1734	combinatorial therapies	1712:1734	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	1	29	theme	multi-branched	85:98	arg1	Glycans					73:79	Glycans	73:79	Glycans	73:79	Glycans are multi-branched sugars that are displayed from lipids and proteins.
32097449	1	29	theme	multi-branched	85:98	arg1	sugars					100:105	multi-branched sugars	85:105	multi-branched sugars that are displayed from lipids and proteins	85:149	Glycans are multi-branched sugars that are displayed from lipids and proteins.
32097449	3	30	theme	aberrant	443:450	arg1	glycosylation					452:464	aberrant glycosylation	443:464	aberrant glycosylation	443:464	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	5	31	theme	binding	830:836	arg1	QxDxNxVxY					847:855	QxDxNxVxY	847:855	QxDxNxVxY	847:855	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	31	theme	binding	830:836	arg1	each					859:862	each	859:862	each	859:862	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	31	theme	binding	830:836	arg1	domains					838:844	six canonical mannose binding domains	808:844	six canonical mannose binding domains (QxDxNxVxY)	808:856	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	0	32	theme	lectins	23:29	arg1	Discovery					0:8	Discovery	0:8	Discovery of antitumor lectins from rainforest tree root transcriptomes.	0:71	Discovery of antitumor lectins from rainforest tree root transcriptomes.
32097449	8	33	theme	biochemical	1385:1395	arg1	tools					1397:1401	novel biochemical tools	1379:1401	novel biochemical tools	1379:1401	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	33	theme	biochemical	1385:1395	arg1	ML6					1331:1333	ML6	1331:1333	ML6	1331:1333	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	33	theme	biochemical	1385:1395	arg1	lectins					1358:1364	other high-valence lectins	1339:1364	other high-valence lectins	1339:1364	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	5	34	theme	amino	878:882	arg1	sequence					889:896	a unique amino acid sequence	869:896	a unique amino acid sequence	869:896	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	3	35	theme	various	395:401	arg1	diseases					409:416	various human diseases	395:416	various human diseases; including cancer, where aberrant glycosylation drives malignancy	395:482	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	3	35	theme	various	395:401	arg1	cancer					429:434	cancer	429:434	cancer	429:434	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	6	36	theme	potent	967:972	arg1	times					956:960	>105 times	951:960	>105 times more potent than standard chemotherapeutics	951:1004	Remarkably, ML6 displays antitumor activity that is >105 times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells.
32097449	8	37	theme	glycomic	1420:1427	arg1	signature					1429:1437	the glycomic signature	1416:1437	the glycomic signature of different human tumors	1416:1463	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	4	38	theme	rapid	657:661	arg1	death					675:679	potent and rapid cancer cell death	646:679	potent and rapid cancer cell death	646:679	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	3	39	theme	human	403:407	arg1	diseases					409:416	various human diseases	395:416	various human diseases; including cancer, where aberrant glycosylation drives malignancy	395:482	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	3	39	theme	human	403:407	arg1	cancer					429:434	cancer	429:434	cancer	429:434	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	9	40	theme	fight	1739:1743	arg1	resistance					1757:1766	fight therapeutic resistance	1739:1766	fight therapeutic resistance in cancer	1739:1776	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	8	41	theme	high-valence	1345:1356	arg1	tools					1397:1401	novel biochemical tools	1379:1401	novel biochemical tools	1379:1401	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	41	theme	high-valence	1345:1356	arg1	ML6					1331:1333	ML6	1331:1333	ML6	1331:1333	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	41	theme	high-valence	1345:1356	arg1	lectins					1358:1364	other high-valence lectins	1339:1364	other high-valence lectins	1339:1364	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	7	42	theme	incomplete	1282:1291	arg1	glycans					1306:1312	naïve and incomplete cell surface glycans	1272:1312	naïve and incomplete cell surface glycans	1272:1312	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	0	43	theme	rainforest	36:45	arg1	transcriptomes					57:70	rainforest tree root transcriptomes	36:70	rainforest tree root transcriptomes	36:70	Discovery of antitumor lectins from rainforest tree root transcriptomes.
32097449	9	44	theme	therapeutic	1745:1755	arg1	resistance					1757:1766	fight therapeutic resistance	1739:1766	fight therapeutic resistance in cancer	1739:1776	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	6	45	theme	non-transformed	1054:1068	arg1	cells					1079:1083	non-transformed, healthy cells	1054:1083	non-transformed, healthy cells	1054:1083	Remarkably, ML6 displays antitumor activity that is >105 times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells.
32097449	2	46	theme	pathways	251:258	arg1	myriad					222:227	a myriad	220:227	a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival	220:325	Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival.
32097449	4	47	theme	cell	670:673	arg1	death					675:679	potent and rapid cancer cell death	646:679	potent and rapid cancer cell death	646:679	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	7	48	from	studies	1149:1155	arg1	results					1121:1127	results	1121:1127	results from glycan binding studies	1121:1155	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	2	49	theme	polysaccharide	174:187	arg1	structures					189:198	their diverse polysaccharide structures	160:198	their diverse polysaccharide structures	160:198	Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival.
32097449	2	50	theme	signaling	241:249	arg1	pathways					251:258	cellular signaling pathways	232:258	cellular signaling pathways involved in development, growth, immuno-communication and survival	232:325	Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival.
32097449	4	51	theme	cancer	663:668	arg1	death					675:679	potent and rapid cancer cell death	646:679	potent and rapid cancer cell death	646:679	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	0	52	theme	root	52:55	arg1	transcriptomes					57:70	rainforest tree root transcriptomes	36:70	rainforest tree root transcriptomes	36:70	Discovery of antitumor lectins from rainforest tree root transcriptomes.
32097449	5	53	theme	canonical	812:820	arg1	QxDxNxVxY					847:855	QxDxNxVxY	847:855	QxDxNxVxY	847:855	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	53	theme	canonical	812:820	arg1	each					859:862	each	859:862	each	859:862	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	53	theme	canonical	812:820	arg1	domains					838:844	six canonical mannose binding domains	808:844	six canonical mannose binding domains (QxDxNxVxY)	808:856	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	2	54	theme	diverse	166:172	arg1	structures					189:198	their diverse polysaccharide structures	160:198	their diverse polysaccharide structures	160:198	Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival.
32097449	2	55	theme	cellular	232:239	arg1	pathways					251:258	cellular signaling pathways	232:258	cellular signaling pathways involved in development, growth, immuno-communication and survival	232:325	Through their diverse polysaccharide structures they can potentiate a myriad of cellular signaling pathways involved in development, growth, immuno-communication and survival.
32097449	0	56	theme	tree	47:50	arg1	transcriptomes					57:70	rainforest tree root transcriptomes	36:70	rainforest tree root transcriptomes	36:70	Discovery of antitumor lectins from rainforest tree root transcriptomes.
32097449	9	57	from	advances	1680:1687	arg1	way					1696:1698	the way we approach combinatorial therapies to fight therapeutic resistance in cancer	1692:1776	the way we approach combinatorial therapies to fight therapeutic resistance in cancer	1692:1776	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	6	58	theme	antitumor	924:932	arg1	activity					934:941	antitumor activity	924:941	antitumor activity that is >105 times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells	924:1083	Remarkably, ML6 displays antitumor activity that is >105 times more potent than standard chemotherapeutics, while being almost completely inactive towards non-transformed, healthy cells.
32097449	9	59	theme	microorganisms	1639:1652	arg1	defenses					1617:1624	the changing defenses	1604:1624	the changing defenses of competing microorganisms	1604:1652	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	8	60	theme	rational	1480:1487	arg1	design					1489:1494	the rational design	1476:1494	the rational design of carbohydrate-directed therapies	1476:1529	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	61	theme	tumors	1458:1463	arg1	signature					1429:1437	the glycomic signature	1416:1437	the glycomic signature of different human tumors	1416:1463	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	5	62	from	unusual	793:799	arg1	QxDxNxVxY					847:855	QxDxNxVxY	847:855	QxDxNxVxY	847:855	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	62	from	unusual	793:799	arg1	each					859:862	each	859:862	each	859:862	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	5	62	from	unusual	793:799	arg1	domains					838:844	six canonical mannose binding domains	808:844	six canonical mannose binding domains (QxDxNxVxY)	808:856	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	8	63	theme	human	1452:1456	arg1	tumors					1458:1463	different human tumors	1442:1463	different human tumors	1442:1463	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	9	64	theme	fundamental	1668:1678	arg1	advances					1680:1687	fundamental advances	1668:1687	fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer	1668:1776	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	7	65	theme	surface	1298:1304	arg1	glycans					1306:1312	naïve and incomplete cell surface glycans	1272:1312	naïve and incomplete cell surface glycans	1272:1312	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	5	66	theme	gene	714:717	arg1	models					719:724	gene models	714:724	gene models identified in a tropical rainforest tree root transcriptome	714:784	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	8	67	theme	therapies	1521:1529	arg1	design					1489:1494	the rational design	1476:1494	the rational design of carbohydrate-directed therapies	1476:1529	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	8	68	theme	different	1442:1450	arg1	tumors					1458:1463	different human tumors	1442:1463	different human tumors	1442:1463	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	7	69	with	combination	1104:1114	arg1	results					1121:1127	results	1121:1127	results from glycan binding studies	1121:1155	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	9	70	dep	way	1696:1698	arg1	approach					1703:1710	approach	1703:1710	approach combinatorial therapies to fight therapeutic resistance in cancer	1703:1776	Further, understanding how nature evolves proteins, like ML6, to combat the changing defenses of competing microorganisms may allow for fundamental advances in the way we approach combinatorial therapies to fight therapeutic resistance in cancer.
32097449	8	71	theme	carbohydrate-directed	1499:1519	arg1	therapies					1521:1529	carbohydrate-directed therapies	1499:1529	carbohydrate-directed therapies	1499:1529	Thus, ML6 and other high-valence lectins may serve as novel biochemical tools to elucidate the glycomic signature of different human tumors and aid in the rational design of carbohydrate-directed therapies.
32097449	5	72	theme	acid	884:887	arg1	sequence					889:896	a unique amino acid sequence	869:896	a unique amino acid sequence	869:896	This lectin was engineered from gene models identified in a tropical rainforest tree root transcriptome and is unusual in its six canonical mannose binding domains (QxDxNxVxY), each with a unique amino acid sequence.
32097449	4	73	theme	potent	646:651	arg1	death					675:679	potent and rapid cancer cell death	646:679	potent and rapid cancer cell death	646:679	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	3	74	theme	glycan	360:365	arg1	synthesis					367:375	glycan synthesis	360:375	glycan synthesis	360:375	Not surprisingly, disruption of glycan synthesis is fundamental to various human diseases; including cancer, where aberrant glycosylation drives malignancy.
32097449	4	75	theme	novel	520:524	arg1	ML6					550:552	ML6	550:552	ML6	550:552	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	4	75	theme	novel	520:524	arg1	lectin					542:547	a novel mannose-binding lectin	518:547	a novel mannose-binding lectin	518:547	Here, we report the discovery of a novel mannose-binding lectin, ML6, which selectively recognizes and binds to these irregular tumor-specific glycans to elicit potent and rapid cancer cell death.
32097449	0	76	theme	antitumor	13:21	arg1	lectins					23:29	antitumor lectins	13:29	antitumor lectins	13:29	Discovery of antitumor lectins from rainforest tree root transcriptomes.
32097449	7	77	theme	cell	1293:1296	arg1	glycans					1306:1312	naïve and incomplete cell surface glycans	1272:1312	naïve and incomplete cell surface glycans	1272:1312	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32097449	7	78	theme	divergent	1228:1236	arg1	pathways					1252:1259	divergent glycosylation pathways	1228:1259	divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors	1228:1322	This activity, in combination with results from glycan binding studies, suggests ML6 differentiates healthy and malignant cells by exploiting divergent glycosylation pathways that yield naïve and incomplete cell surface glycans in tumors.
32692906	3	0	theme	extended	692:699	arg1	biosynthesis					710:721	Normal extended O-glycan biosynthesis	685:721	Normal extended O-glycan biosynthesis	685:721	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	1	1	theme	apoptosis-inducing	166:183	arg1	TRAIL					193:197	TRAIL	193:197	TRAIL	193:197	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	1	theme	apoptosis-inducing	166:183	arg1	ligand					185:190	The TNF-related apoptosis-inducing ligand	150:190	The TNF-related apoptosis-inducing ligand (TRAIL)	150:198	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	2	theme	death	268:272	arg1	receptors					274:282	the O-glycosylated death receptors	249:282	the O-glycosylated death receptors (DR4 and DR5)	249:296	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	2	theme	death	268:272	arg1	DR5					293:295	DR5	293:295	DR5	293:295	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	2	theme	death	268:272	arg1	DR4					285:287	DR4	285:287	DR4	285:287	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	0	3	theme	TRAIL-induced	68:80	arg1	apoptosis					82:90	TRAIL-induced apoptosis	68:90	TRAIL-induced apoptosis	68:90	O-glycans on death receptors in cells modulate their sensitivity to TRAIL-induced apoptosis through affecting on their stability and oligomerization.
32692906	5	4	theme	TRAIL	1102:1106	arg1	treatment					1108:1116	TRAIL treatment	1102:1116	TRAIL treatment	1102:1116	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	7	5	theme	DR4	1590:1592	arg1	activity					1605:1612	DR4 and/or DR5 activity	1590:1612	DR4 and/or DR5 activity	1590:1612	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	7	6	from	structures	1424:1433	arg1	surface					1443:1449	cell surface	1438:1449	cell surface	1438:1449	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	3	7	theme	β3	827:828	arg1	T-synthase					853:862	T-synthase	853:862	T-synthase	853:862	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	3	7	theme	β3	827:828	arg1	Galactosyltransferase					830:850	Core 1 β3 Galactosyltransferase	820:850	Core 1 β3 Galactosyltransferase (T-synthase)	820:863	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	0	8	from	O-glycans	0:8	arg1	receptors					19:27	death receptors	13:27	death receptors in cells	13:36	O-glycans on death receptors in cells modulate their sensitivity to TRAIL-induced apoptosis through affecting on their stability and oligomerization.
32692906	2	9	theme	molecular	575:583	arg1	mechanisms					585:594	molecular mechanisms	575:594	molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans	575:667	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	7	10	theme	cell	1548:1551	arg1	advantages					1562:1571	tumor cell survival advantages	1542:1571	tumor cell survival advantages	1542:1571	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	6	11	theme	DR5	1347:1349	arg1	stability					1326:1334	stability	1326:1334	stability	1326:1334	Mechanistically, Tn/STn antigens impair homo-oligomerization and stability of DR4 and DR5.
32692906	6	11	theme	DR5	1347:1349	arg1	homo-oligomerization					1301:1320	homo-oligomerization	1301:1320	homo-oligomerization	1301:1320	Mechanistically, Tn/STn antigens impair homo-oligomerization and stability of DR4 and DR5.
32692906	5	12	theme	tumor	1058:1062	arg1	cells					1064:1068	tumor cells	1058:1068	tumor cells	1058:1068	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	1	13	gly	O-glycosylated	253:266	arg1	receptors					274:282	the O-glycosylated death receptors	249:282	the O-glycosylated death receptors (DR4 and DR5)	249:296	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	13	gly	O-glycosylated	253:266	arg1	DR5					293:295	DR5	293:295	DR5	293:295	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	13	gly	O-glycosylated	253:266	arg1	DR4					285:287	DR4	285:287	DR4	285:287	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	7	14	theme	apoptotic	1481:1489	arg1	stimuli					1491:1497	apoptotic stimuli	1481:1497	apoptotic stimuli	1481:1497	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	3	15	theme	Core	820:823	arg1	T-synthase					853:862	T-synthase	853:862	T-synthase	853:862	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	3	15	theme	Core	820:823	arg1	Galactosyltransferase					830:850	Core 1 β3 Galactosyltransferase	820:850	Core 1 β3 Galactosyltransferase (T-synthase)	820:863	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	2	16	theme	tumor	623:627	arg1	cells					629:633	tumor cells	623:633	tumor cells	623:633	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	2	17	theme	truncated	450:458	arg1	O-glycans					460:468	truncated O-glycans	450:468	truncated O-glycans	450:468	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	3	18	theme	O-glycan	701:708	arg1	biosynthesis					710:721	Normal extended O-glycan biosynthesis	685:721	Normal extended O-glycan biosynthesis	685:721	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	2	19	theme	advantages	608:617	arg1	terms					599:603	terms	599:603	terms of advantages	599:617	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	7	20	theme	O-glycan	1415:1422	arg1	structures					1424:1433	O-glycan structures	1415:1433	O-glycan structures on cell surface	1415:1449	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	4	21	theme	O-glycans	992:1000	arg1	role					984:987	the role	980:987	the role of O-glycans in TRAIL-induced apoptosis	980:1027	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	4	22	theme	STn	958:960	arg1	antigens					962:969	Tn and STn antigens	951:969	Tn and STn antigens	951:969	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	5	23	theme	wild-type	1141:1149	arg1	Cosmc					1151:1155	wild-type Cosmc	1141:1155	wild-type Cosmc	1141:1155	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	3	24	theme	specific	741:748	arg1	chaperone					760:768	a specific molecular chaperone	739:768	a specific molecular chaperone Cosmc	739:774	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	2	25	theme	truncated	649:657	arg1	O-glycans					659:667	these truncated O-glycans	643:667	these truncated O-glycans	643:667	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	7	26	theme	tumor	1542:1546	arg1	advantages					1562:1571	tumor cell survival advantages	1542:1571	tumor cell survival advantages	1542:1571	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	7	27	theme	cell	1438:1441	arg1	surface					1443:1449	cell surface	1438:1449	cell surface	1438:1449	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	4	28	theme	TRAIL-induced	1005:1017	arg1	apoptosis					1019:1027	TRAIL-induced apoptosis	1005:1027	TRAIL-induced apoptosis	1005:1027	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	3	29	theme	molecular	750:758	arg1	chaperone					760:768	a specific molecular chaperone	739:768	a specific molecular chaperone Cosmc	739:774	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	2	30	dep	Sialyl-Tn	498:506	arg1	STn					534:536	STn	534:536	STn	534:536	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	2	30	dep	Sialyl-Tn	498:506	arg1	Siaα2-6GalNAcα1-Ser/Thr					509:531	Siaα2-6GalNAcα1-Ser/Thr	509:531	Siaα2-6GalNAcα1-Ser/Thr	509:531	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	7	31	theme	first	1380:1384	arg1	insight					1398:1404	the first mechanistic insight	1376:1404	the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity	1376:1612	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	2	32	theme	Human	414:418	arg1	cells					430:434	Human carcinoma cells	414:434	Human carcinoma cells	414:434	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	2	33	contain	have	638:641	arg2	O-glycans					659:667	these truncated O-glycans	643:667	these truncated O-glycans	643:667	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	2	33	contain	have	638:641	arg1	cells					629:633	tumor cells	623:633	tumor cells	623:633	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	5	34	theme	Tn	1044:1045	arg1	Expression					1030:1039	Expression	1030:1039	Expression of Tn and STn in tumor cells	1030:1068	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	7	35	theme	mechanistic	1386:1396	arg1	insight					1398:1404	the first mechanistic insight	1376:1404	the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity	1376:1612	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	2	36	from	mechanisms	585:594	arg1	terms					599:603	terms	599:603	terms of advantages	599:617	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	5	37	theme	normal	1189:1194	arg1	O-glycans					1205:1213	normal extended O-glycans	1189:1213	normal extended O-glycans	1189:1213	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	0	38	theme	death	13:17	arg1	receptors					19:27	death receptors	13:27	death receptors in cells	13:36	O-glycans on death receptors in cells modulate their sensitivity to TRAIL-induced apoptosis through affecting on their stability and oligomerization.
32692906	4	39	from	role	984:987	arg1	apoptosis					1019:1027	TRAIL-induced apoptosis	1005:1027	TRAIL-induced apoptosis	1005:1027	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	4	40	from	mutations	906:914	arg1	Cosmc					919:923	Cosmc	919:923	Cosmc	919:923	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	6	41	theme	DR4	1339:1341	arg1	stability					1326:1334	stability	1326:1334	stability	1326:1334	Mechanistically, Tn/STn antigens impair homo-oligomerization and stability of DR4 and DR5.
32692906	6	41	theme	DR4	1339:1341	arg1	homo-oligomerization					1301:1320	homo-oligomerization	1301:1320	homo-oligomerization	1301:1320	Mechanistically, Tn/STn antigens impair homo-oligomerization and stability of DR4 and DR5.
32692906	7	42	theme	DR5	1601:1603	arg1	activity					1605:1612	DR4 and/or DR5 activity	1590:1612	DR4 and/or DR5 activity	1590:1612	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	4	43	theme	tumor	879:883	arg1	lines					890:894	tumor cell lines	879:894	tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens	879:969	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	1	44	theme	phenomenon	390:399	arg1	complex					405:411	complex	405:411	complex	405:411	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	44	theme	phenomenon	390:399	arg1	attributes					371:380	the attributes	367:380	the attributes of this phenomenon	367:399	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	6	45	theme	Tn/STn	1278:1283	arg1	antigens					1285:1292	Tn/STn antigens	1278:1292	Tn/STn antigens	1278:1292	Mechanistically, Tn/STn antigens impair homo-oligomerization and stability of DR4 and DR5.
32692906	2	46	gly	glycoproteins	556:568	arg1	glycoproteins					556:568	their surface glycoproteins	542:568	their surface glycoproteins	542:568	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	1	47	theme	cells	349:353	arg1	apoptosis					336:344	TRAIL-induced apoptosis	322:344	TRAIL-induced apoptosis of cells	322:353	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	3	48	theme	chaperone	760:768	arg1	Cosmc					770:774	a specific molecular chaperone Cosmc	739:774	a specific molecular chaperone Cosmc	739:774	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	1	49	theme	TRAIL-induced	322:334	arg1	apoptosis					336:344	TRAIL-induced apoptosis	322:344	TRAIL-induced apoptosis of cells	322:353	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	50	from	apoptosis	209:217	arg1	cells					222:226	cells	222:226	cells	222:226	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	3	51	theme	Normal	685:690	arg1	biosynthesis					710:721	Normal extended O-glycan biosynthesis	685:721	Normal extended O-glycan biosynthesis	685:721	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	5	52	theme	TRAIL	1244:1248	arg1	treatment					1250:1258	TRAIL treatment	1244:1258	TRAIL treatment	1244:1258	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	2	53	theme	surface	548:554	arg1	glycoproteins					556:568	their surface glycoproteins	542:568	their surface glycoproteins	542:568	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	5	54	theme	STn	1051:1053	arg1	Expression					1030:1039	Expression	1030:1039	Expression of Tn and STn in tumor cells	1030:1068	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	3	55	theme	correct	801:807	arg1	folding					809:815	the correct folding	797:815	the correct folding of Core 1 β3 Galactosyltransferase (T-synthase)	797:863	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	4	56	theme	cell	885:888	arg1	lines					890:894	tumor cell lines	879:894	tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens	879:969	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	5	57	from	Expression	1030:1039	arg1	cells					1064:1068	tumor cells	1058:1068	tumor cells	1058:1068	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	5	58	theme	tumor	1164:1168	arg1	cells					1170:1174	these tumor cells	1158:1174	these tumor cells	1158:1174	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	3	59	theme	Galactosyltransferase	830:850	arg1	folding					809:815	the correct folding	797:815	the correct folding of Core 1 β3 Galactosyltransferase (T-synthase)	797:863	Normal extended O-glycan biosynthesis is regulated by a specific molecular chaperone Cosmc through assisting of the correct folding of Core 1 β3 Galactosyltransferase (T-synthase).
32692906	5	60	theme	extended	1196:1203	arg1	O-glycans					1205:1213	normal extended O-glycans	1189:1213	normal extended O-glycans	1189:1213	Expression of Tn and STn in tumor cells attenuates their sensitivity to TRAIL treatment; when transfected with wild-type Cosmc, these tumor cells thus express normal extended O-glycans and become more sensitive to TRAIL treatment.
32692906	4	61	dep	lines	890:894	arg1	expressing					940:949	expressing	940:949	therefore expressing Tn and STn antigens	930:969	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	4	61	dep	lines	890:894	arg1	harboring					896:904	harboring	896:904	harboring mutations in Cosmc	896:923	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	1	62	dep	receptors	274:282	arg1	receptors					274:282	the O-glycosylated death receptors	249:282	the O-glycosylated death receptors (DR4 and DR5)	249:296	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	62	dep	receptors	274:282	arg1	DR5					293:295	DR5	293:295	DR5	293:295	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	62	dep	receptors	274:282	arg1	DR4					285:287	DR4	285:287	DR4	285:287	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	7	63	theme	survival	1553:1560	arg1	advantages					1562:1571	tumor cell survival advantages	1542:1571	tumor cell survival advantages	1542:1571	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	4	64	theme	Tn	951:952	arg1	antigens					962:969	Tn and STn antigens	951:969	Tn and STn antigens	951:969	Here, we use tumor cell lines harboring mutations in Cosmc, and therefore expressing Tn and STn antigens to study the role of O-glycans in TRAIL-induced apoptosis.
32692906	0	65	from	receptors	19:27	arg1	cells					32:36	cells	32:36	cells	32:36	O-glycans on death receptors in cells modulate their sensitivity to TRAIL-induced apoptosis through affecting on their stability and oligomerization.
32692906	2	66	theme	carcinoma	420:428	arg1	cells					430:434	Human carcinoma cells	414:434	Human carcinoma cells	414:434	Human carcinoma cells often express truncated O-glycans, Tn (GalNAcα1-Ser/Thr), and Sialyl-Tn (Siaα2-6GalNAcα1-Ser/Thr, STn) on their surface glycoproteins, yet molecular mechanisms in terms of advantages for tumor cells to have these truncated O-glycans remain elusive.
32692906	7	67	theme	Tn/STn	1525:1530	arg1	expression					1511:1520	expression	1511:1520	expression of Tn/STn	1511:1530	These results represent the first mechanistic insight into how O-glycan structures on cell surface modulate their sensitivity to apoptotic stimuli, suggesting expression of Tn/STn may offer tumor cell survival advantages through altering DR4 and/or DR5 activity.
32692906	1	68	theme	TNF-related	154:164	arg1	TRAIL					193:197	TRAIL	193:197	TRAIL	193:197	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	68	theme	TNF-related	154:164	arg1	ligand					185:190	The TNF-related apoptosis-inducing ligand	150:190	The TNF-related apoptosis-inducing ligand (TRAIL)	150:198	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	69	theme	O-glycosylated	253:266	arg1	receptors					274:282	the O-glycosylated death receptors	249:282	the O-glycosylated death receptors (DR4 and DR5)	249:296	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	69	theme	O-glycosylated	253:266	arg1	DR5					293:295	DR5	293:295	DR5	293:295	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32692906	1	69	theme	O-glycosylated	253:266	arg1	DR4					285:287	DR4	285:287	DR4	285:287	The TNF-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in cells by signaling through the O-glycosylated death receptors (DR4 and DR5), but the sensitivity to TRAIL-induced apoptosis of cells varies, and the attributes of this phenomenon are complex.
32433992	3	0	theme	glycan	484:489	arg1	network					491:497	the glycan network	480:497	the glycan network surrounding an epitope impact the fine glycan processing of antibody targets	480:574	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	5	1	from	apex	887:890	arg1	epitopes					864:871	the PG9 and PG16 glycan-based epitopes	834:871	epitopes	864:871	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	5	1	from	apex	887:890	arg1	dependent					896:904	dependent	896:904	dependent	896:904	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	5	1	from	apex	887:890	arg1	PG9					838:840	the PG9 and PG16 glycan-based epitopes	834:871	PG9	838:840	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	5	2	theme	glycan-based	851:862	arg1	epitopes					864:871	the PG9 and PG16 glycan-based epitopes	834:871	epitopes	864:871	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	0	3	theme	Additions	84:92	arg1	Face					69:72	the Face	65:72	the Face of Glycan Additions and Deletions	65:106	Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
32433992	5	4	theme	surrounding	946:956	arg1	glycans					958:964	the highly conserved surrounding glycans	925:964	the highly conserved surrounding glycans	925:964	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	2	5	theme	glycan	277:282	arg1	processing					284:293	glycan processing	277:293	glycan processing	277:293	Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans.
32433992	6	6	from	parameter	1047:1055	arg1	design					1070:1075	immunogen design	1060:1075	immunogen design	1060:1075	Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
32433992	4	7	theme	cryo-electron	583:595	arg1	microscopy					597:606	cryo-electron microscopy	583:606	cryo-electron microscopy	583:606	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	0	8	theme	Glycan	77:82	arg1	Additions					84:92	Glycan Additions	77:92	Glycan Additions	77:92	Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
32433992	3	9	theme	fine	533:536	arg1	processing					545:554	the fine glycan processing	529:554	the fine glycan processing of antibody targets	529:574	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	4	10	theme	bnAb	708:711	arg1	epitope					713:719	the 2G12 bnAb epitope	699:719	the 2G12 bnAb epitope	699:719	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	0	11	theme	Deletions	98:106	arg1	Face					69:72	the Face	65:72	the Face of Glycan Additions and Deletions	65:106	Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
32433992	4	12	theme	2G12	703:706	arg1	epitope					713:719	the 2G12 bnAb epitope	699:719	the 2G12 bnAb epitope	699:719	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	4	13	theme	glycans	671:677	arg1	importance					657:666	the importance	653:666	the importance of glycans in the formation of the 2G12 bnAb epitope	653:719	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	6	14	theme	important	1037:1045	arg1	parameter					1047:1055	an important parameter	1034:1055	an important parameter in immunogen design	1034:1075	Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
32433992	4	15	from	importance	657:666	arg1	formation					686:694	the formation	682:694	the formation of the 2G12 bnAb epitope	682:719	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	3	16	from	mutations	467:475	arg1	network					491:497	the glycan network	480:497	the glycan network surrounding an epitope impact the fine glycan processing of antibody targets	480:574	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	3	17	theme	envelope	415:422	arg1	trimer					424:429	a stabilized recombinant envelope trimer	390:429	a stabilized recombinant envelope trimer	390:429	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	3	18	theme	antibody	559:566	arg1	targets					568:574	antibody targets	559:574	antibody targets	559:574	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	2	19	theme	glycans	369:375	arg1	absence					346:352	absence	346:352	absence	346:352	Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans.
32433992	2	19	theme	glycans	369:375	arg1	presence					334:341	presence	334:341	presence	334:341	Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans.
32433992	0	20	theme	Envelope	18:25	arg1	Glycans					27:33	HIV-1 Envelope Glycans	12:33	HIV-1 Envelope Glycans	12:33	Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
32433992	5	21	theme	glycans	958:964	arg1	presence					913:920	the presence	909:920	the presence of the highly conserved surrounding glycans	909:964	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	2	22	dep	presence	334:341	arg1	the					330:332	the	330:332	the	330:332	Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans.
32433992	6	23	theme	epitopes	1017:1024	arg1	conservation					996:1007	the conservation	992:1007	the conservation of bnAb epitopes	992:1024	Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
32433992	0	24	theme	HIV-1	12:16	arg1	Glycans					27:33	HIV-1 Envelope Glycans	12:33	HIV-1 Envelope Glycans	12:33	Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
32433992	6	25	theme	Glycan	967:972	arg1	networks					974:981	Glycan networks	967:981	Glycan networks	967:981	Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
32433992	6	26	theme	bnAb	1012:1015	arg1	epitopes					1017:1024	bnAb epitopes	1012:1024	bnAb epitopes	1012:1024	Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
32433992	3	27	theme	stabilized	392:401	arg1	trimer					424:429	a stabilized recombinant envelope trimer	390:429	a stabilized recombinant envelope trimer	390:429	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	4	28	theme	glycan	792:797	arg1	network					799:805	the glycan network	788:805	the glycan network	788:805	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	0	29	theme	Glycans	27:33	arg1	Networks					0:7	Networks	0:7	Networks of HIV-1 Envelope Glycans	0:33	Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
32433992	3	30	theme	recombinant	403:413	arg1	trimer					424:429	a stabilized recombinant envelope trimer	390:429	a stabilized recombinant envelope trimer	390:429	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	4	31	theme	glycan	626:631	arg1	analysis					633:640	site-specific glycan analysis	612:640	site-specific glycan analysis	612:640	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	3	32	theme	targets	568:574	arg1	processing					545:554	the fine glycan processing	529:554	the fine glycan processing of antibody targets	529:574	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	3	33	dep	epitope	514:520	arg1	impact					522:527	impact	522:527	impact	522:527	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	0	34	theme	Antibody	44:51	arg1	Epitopes					53:60	Antibody Epitopes	44:60	Antibody Epitopes	44:60	Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
32433992	1	35	theme	Numerous	109:116	arg1	bnAbs					151:155	bnAbs	151:155	bnAbs	151:155	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	1	35	theme	Numerous	109:116	arg1	antibodies					139:148	Numerous broadly neutralizing antibodies	109:148	Numerous broadly neutralizing antibodies (bnAbs)	109:156	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	5	36	theme	conserved	936:944	arg1	glycans					958:964	the highly conserved surrounding glycans	925:964	the highly conserved surrounding glycans	925:964	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	1	37	theme	broadly	118:124	arg1	bnAbs					151:155	bnAbs	151:155	bnAbs	151:155	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	1	37	theme	broadly	118:124	arg1	antibodies					139:148	Numerous broadly neutralizing antibodies	109:148	Numerous broadly neutralizing antibodies (bnAbs)	109:156	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	3	38	theme	glycan	538:543	arg1	processing					545:554	the fine glycan processing	529:554	the fine glycan processing of antibody targets	529:574	Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets.
32433992	5	39	theme	trimer	880:885	arg1	apex					887:890	the trimer apex	876:890	the trimer apex	876:890	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	4	40	theme	epitope	713:719	arg1	formation					686:694	the formation	682:694	the formation of the 2G12 bnAb epitope	682:719	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	1	41	theme	neutralizing	126:137	arg1	bnAbs					151:155	bnAbs	151:155	bnAbs	151:155	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	1	41	theme	neutralizing	126:137	arg1	antibodies					139:148	Numerous broadly neutralizing antibodies	109:148	Numerous broadly neutralizing antibodies (bnAbs)	109:156	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	1	42	theme	HIV-1	210:214	arg1	spike					225:229	the HIV-1 envelope spike	206:229	the HIV-1 envelope spike	206:229	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	5	43	theme	PG16	846:849	arg1	epitopes					864:871	the PG9 and PG16 glycan-based epitopes	834:871	epitopes	864:871	In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans.
32433992	2	44	theme	Neutralization	232:245	arg1	breadth					247:253	Neutralization breadth	232:253	Neutralization breadth	232:253	Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans.
32433992	4	45	from	variations	774:783	arg1	network					799:805	the glycan network	788:805	the glycan network	788:805	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	2	46	theme	neighboring	357:367	arg1	glycans					369:375	neighboring glycans	357:375	neighboring glycans	357:375	Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans.
32433992	1	47	theme	envelope	216:223	arg1	spike					225:229	the HIV-1 envelope spike	206:229	the HIV-1 envelope spike	206:229	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32433992	4	48	theme	site-specific	612:624	arg1	analysis					633:640	site-specific glycan analysis	612:640	site-specific glycan analysis	612:640	Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network.
32433992	2	49	dep	notable	258:264	arg1	given					266:270	given	266:270	given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans	266:375	Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans.
32433992	1	50	theme	spike	225:229	arg1	glycans					195:201	the glycans	191:201	the glycans of the HIV-1 envelope spike	191:229	Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike.
32825463	4	0	theme	glycans	512:518	arg1	pathway					489:495	the biosynthetic pathway	472:495	the biosynthetic pathway of fucosylated glycans	472:518	However, little is known about how efficiently each unnatural Fuc analog is utilized by enzymes in the biosynthetic pathway of fucosylated glycans.
32825463	5	1	theme	clickable	545:553	arg1	analogs					559:565	three clickable Fuc analogs	539:565	three clickable Fuc analogs with similar but distinct structures	539:602	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	10	2	theme	functions	1529:1537	arg1	detection					1478:1486	specific detection	1469:1486	specific detection of target glycans	1469:1504	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	2	theme	functions	1529:1537	arg1	inhibition					1509:1518	inhibition	1509:1518	inhibition of their functions	1509:1537	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	5	3	theme	protein	659:665	arg1	specificity					667:677	protein specificity	659:677	protein specificity	659:677	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	5	4	theme	cellular	612:619	arg1	glycans					621:627	cellular glycans	612:627	cellular glycans	612:627	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	9	5	theme	POFUT	1102:1106	arg1	structures					1108:1117	POFUT structures	1102:1117	POFUT structures	1102:1117	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	9	6	contain	have	1119:1122	arg2	space					1133:1137	a larger space	1124:1137	a larger space around their Fuc binding sites	1124:1168	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	9	6	contain	have	1119:1122	arg1	structures					1108:1117	POFUT structures	1102:1117	POFUT structures	1102:1117	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	10	7	theme	specific	1469:1476	arg1	detection					1478:1486	specific detection	1469:1486	specific detection of target glycans	1469:1504	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	2	8	gly	fucosylated	184:194	arg1	glycans					196:202	fucosylated glycans	184:202	fucosylated glycans	184:202	Alterations in levels of fucosylated glycans are associated with various diseases.
32825463	10	9	theme	Fuc	1254:1256	arg1	analogs					1258:1264	Fuc analogs	1254:1264	Fuc analogs	1254:1264	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	4	10	used	utilized	449:456	arg2	analog					439:444	each unnatural Fuc analog	420:444	each unnatural Fuc analog	420:444	However, little is known about how efficiently each unnatural Fuc analog is utilized by enzymes in the biosynthetic pathway of fucosylated glycans.
32825463	10	11	with	detection	1216:1224	arg1	analogs					1258:1264	Fuc analogs	1254:1264	Fuc analogs	1254:1264	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	4	12	theme	unnatural	425:433	arg1	analog					439:444	each unnatural Fuc analog	420:444	each unnatural Fuc analog	420:444	However, little is known about how efficiently each unnatural Fuc analog is utilized by enzymes in the biosynthetic pathway of fucosylated glycans.
32825463	1	13	theme	Fucosylated	68:78	arg1	glycans					80:86	Fucosylated glycans	68:86	Fucosylated glycans	68:86	Fucosylated glycans critically regulate the physiological functions of proteins and cells.
32825463	5	14	with	analogs	559:565	arg1	structures					593:602	similar but distinct structures	572:602	similar but distinct structures	572:602	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	4	15	theme	biosynthetic	476:487	arg1	pathway					489:495	the biosynthetic pathway	472:495	the biosynthetic pathway of fucosylated glycans	472:518	However, little is known about how efficiently each unnatural Fuc analog is utilized by enzymes in the biosynthetic pathway of fucosylated glycans.
32825463	5	16	theme	different	634:642	arg1	efficiency					644:653	different efficiency	634:653	different efficiency	634:653	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	6	17	theme	O-Fuc	723:727	arg1	glycans					729:735	O-Fuc glycans	723:735	O-Fuc glycans	723:735	For instance, 6-alkynyl (Alk)-Fuc modified O-Fuc glycans much more efficiently than 7-Alk-Fuc.
32825463	9	18	theme	Fuc	1065:1067	arg1	analogs					1069:1075	all Fuc analogs	1061:1075	all Fuc analogs	1061:1075	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	4	19	theme	fucosylated	500:510	arg1	glycans					512:518	fucosylated glycans	500:518	fucosylated glycans	500:518	However, little is known about how efficiently each unnatural Fuc analog is utilized by enzymes in the biosynthetic pathway of fucosylated glycans.
32825463	2	20	from	Alterations	159:169	arg1	levels					174:179	levels	174:179	levels of fucosylated glycans	174:202	Alterations in levels of fucosylated glycans are associated with various diseases.
32825463	10	21	theme	analogs	1457:1463	arg1	design					1435:1440	design	1435:1440	design of novel sugar analogs	1435:1463	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	9	22	theme	larger	1126:1131	arg1	space					1133:1137	a larger space	1124:1137	a larger space around their Fuc binding sites	1124:1168	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	3	23	gly	fucosylated	285:295	arg1	glycans					297:303	fucosylated glycans	285:303	fucosylated glycans	285:303	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	3	24	theme	functional	260:269	arg1	modulation					271:280	functional modulation	260:280	functional modulation	260:280	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	5	25	theme	distinct	584:591	arg1	structures					593:602	similar but distinct structures	572:602	similar but distinct structures	572:602	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	10	26	theme	GDP	1325:1327	arg1	form					1329:1332	GDP form	1325:1332	GDP form	1325:1332	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	0	27	theme	Differential	0:11	arg1	Labeling					13:20	Differential Labeling	0:20	Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs	0:65	Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs.
32825463	10	28	theme	target	1491:1496	arg1	glycans					1498:1504	target glycans	1491:1504	target glycans	1491:1504	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	29	theme	novel	1445:1449	arg1	analogs					1457:1463	novel sugar analogs	1445:1463	novel sugar analogs	1445:1463	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	9	30	theme	binding	1156:1162	arg1	sites					1164:1168	their Fuc binding sites	1146:1168	their Fuc binding sites	1146:1168	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	0	31	theme	Glycoproteins	25:37	arg1	Labeling					13:20	Differential Labeling	0:20	Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs	0:65	Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs.
32825463	3	32	theme	chemical	306:313	arg1	approaches					323:332	chemical biology approaches	306:332	chemical biology approaches using fucose (Fuc) analogs	306:359	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	1	33	theme	physiological	112:124	arg1	functions					126:134	the physiological functions	108:134	the physiological functions of proteins and cells	108:156	Fucosylated glycans critically regulate the physiological functions of proteins and cells.
32825463	6	34	theme	Alk	705:707	arg1	-Fuc					709:712	6-alkynyl (Alk)-Fuc	694:712	6-alkynyl (Alk)-Fuc	694:712	For instance, 6-alkynyl (Alk)-Fuc modified O-Fuc glycans much more efficiently than 7-Alk-Fuc.
32825463	3	35	theme	biology	315:321	arg1	approaches					323:332	chemical biology approaches	306:332	chemical biology approaches using fucose (Fuc) analogs	306:359	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	6	36	theme	6-alkynyl	694:702	arg1	-Fuc					709:712	6-alkynyl (Alk)-Fuc	694:712	6-alkynyl (Alk)-Fuc	694:712	For instance, 6-alkynyl (Alk)-Fuc modified O-Fuc glycans much more efficiently than 7-Alk-Fuc.
32825463	9	37	theme	Fuc	1152:1154	arg1	sites					1164:1168	their Fuc binding sites	1146:1168	their Fuc binding sites	1146:1168	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	10	38	theme	sugar	1451:1455	arg1	analogs					1457:1463	novel sugar analogs	1445:1463	novel sugar analogs	1445:1463	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	0	39	theme	Alkynyl	44:50	arg1	Analogs					59:65	Alkynyl Fucose Analogs	44:65	Alkynyl Fucose Analogs	44:65	Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs.
32825463	8	40	theme	fucosyltransferase	887:904	arg1	assays					906:911	Comprehensive in vitro fucosyltransferase assays	864:911	Comprehensive in vitro fucosyltransferase assays	864:911	Comprehensive in vitro fucosyltransferase assays revealed that 7-Alk-Fuc is commonly tolerated by most fucosyltransferases.
32825463	3	41	theme	glycans	297:303	arg1	detection					246:254	detection	246:254	detection	246:254	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	3	41	theme	glycans	297:303	arg1	modulation					271:280	functional modulation	260:280	functional modulation	260:280	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	2	42	theme	glycans	196:202	arg1	levels					174:179	levels	174:179	levels of fucosylated glycans	174:202	Alterations in levels of fucosylated glycans are associated with various diseases.
32825463	4	43	gly	fucosylated	500:510	arg1	glycans					512:518	fucosylated glycans	500:518	fucosylated glycans	500:518	However, little is known about how efficiently each unnatural Fuc analog is utilized by enzymes in the biosynthetic pathway of fucosylated glycans.
32825463	4	44	theme	Fuc	435:437	arg1	analog					439:444	each unnatural Fuc analog	420:444	each unnatural Fuc analog	420:444	However, little is known about how efficiently each unnatural Fuc analog is utilized by enzymes in the biosynthetic pathway of fucosylated glycans.
32825463	2	45	theme	fucosylated	184:194	arg1	glycans					196:202	fucosylated glycans	184:202	fucosylated glycans	184:202	Alterations in levels of fucosylated glycans are associated with various diseases.
32825463	5	46	theme	Fuc	555:557	arg1	analogs					559:565	three clickable Fuc analogs	539:565	three clickable Fuc analogs with similar but distinct structures	539:602	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	9	47	theme	protein	1007:1013	arg1	POFUTs					1038:1043	both protein O-fucosyltransferases (POFUTs)	1002:1044	both protein O-fucosyltransferases (POFUTs)	1002:1044	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	10	48	theme	glycans	1498:1504	arg1	detection					1478:1486	specific detection	1469:1486	specific detection of target glycans	1469:1504	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	48	theme	glycans	1498:1504	arg1	inhibition					1509:1518	inhibition	1509:1518	inhibition of their functions	1509:1537	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	3	49	theme	fucose	340:345	arg1	analogs					353:359	fucose (Fuc) analogs	340:359	fucose (Fuc) analogs	340:359	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	8	50	dep	in	878:879	arg1	vitro					881:885	vitro	881:885	vitro	881:885	Comprehensive in vitro fucosyltransferase assays revealed that 7-Alk-Fuc is commonly tolerated by most fucosyltransferases.
32825463	0	51	theme	Fucose	52:57	arg1	Analogs					59:65	Alkynyl Fucose Analogs	44:65	Alkynyl Fucose Analogs	44:65	Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs.
32825463	3	52	theme	fucosylated	285:295	arg1	glycans					297:303	fucosylated glycans	285:303	fucosylated glycans	285:303	For detection and functional modulation of fucosylated glycans, chemical biology approaches using fucose (Fuc) analogs are useful.
32825463	0	53	with	Labeling	13:20	arg1	Analogs					59:65	Alkynyl Fucose Analogs	44:65	Alkynyl Fucose Analogs	44:65	Differential Labeling of Glycoproteins with Alkynyl Fucose Analogs.
32825463	1	54	theme	proteins	139:146	arg1	functions					126:134	the physiological functions	108:134	the physiological functions of proteins and cells	108:156	Fucosylated glycans critically regulate the physiological functions of proteins and cells.
32825463	7	55	theme	GDP-6-Alk-Fuc	788:800	arg1	higher					829:834	higher	829:834	higher	829:834	The level of GDP-6-Alk-Fuc produced in cells was also higher than that of GDP-7-Alk-Fuc.
32825463	7	55	theme	GDP-6-Alk-Fuc	788:800	arg1	level					779:783	The level	775:783	The level of GDP-6-Alk-Fuc produced in cells	775:818	The level of GDP-6-Alk-Fuc produced in cells was also higher than that of GDP-7-Alk-Fuc.
32825463	2	56	theme	various	224:230	arg1	diseases					232:239	various diseases	224:239	various diseases	224:239	Alterations in levels of fucosylated glycans are associated with various diseases.
32825463	10	57	gly	fucosylated	1229:1239	arg1	glycans					1241:1247	fucosylated glycans	1229:1247	fucosylated glycans	1229:1247	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	5	58	theme	similar	572:578	arg1	structures					593:602	similar but distinct structures	572:602	similar but distinct structures	572:602	We show here that three clickable Fuc analogs with similar but distinct structures labeled cellular glycans with different efficiency and protein specificity.
32825463	10	59	theme	cellular	1285:1292	arg1	transport					1335:1343	transport	1335:1343	transport into the ER or Golgi	1335:1364	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	59	theme	cellular	1285:1292	arg1	steps					1294:1298	multiple cellular steps	1276:1298	multiple cellular steps	1276:1298	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	59	theme	cellular	1285:1292	arg1	conversion					1311:1320	conversion	1311:1320	conversion to GDP form	1311:1332	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	59	theme	cellular	1285:1292	arg1	utilization					1371:1381	utilization	1371:1381	utilization by each fucosyltransferase	1371:1408	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	60	theme	glycans	1241:1247	arg1	detection					1216:1224	detection	1216:1224	detection	1216:1224	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	60	theme	glycans	1241:1247	arg1	labeling					1203:1210	labeling	1203:1210	labeling	1203:1210	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	61	dep	ER	1354:1355	arg1	the					1350:1352	the	1350:1352	the	1350:1352	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	8	62	theme	most	962:965	arg1	fucosyltransferases					967:985	most fucosyltransferases	962:985	most fucosyltransferases	962:985	Comprehensive in vitro fucosyltransferase assays revealed that 7-Alk-Fuc is commonly tolerated by most fucosyltransferases.
32825463	1	63	theme	cells	152:156	arg1	functions					126:134	the physiological functions	108:134	the physiological functions of proteins and cells	108:156	Fucosylated glycans critically regulate the physiological functions of proteins and cells.
32825463	10	64	theme	multiple	1276:1283	arg1	transport					1335:1343	transport	1335:1343	transport into the ER or Golgi	1335:1364	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	64	theme	multiple	1276:1283	arg1	steps					1294:1298	multiple cellular steps	1276:1298	multiple cellular steps	1276:1298	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	64	theme	multiple	1276:1283	arg1	conversion					1311:1320	conversion	1311:1320	conversion to GDP form	1311:1332	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	64	theme	multiple	1276:1283	arg1	utilization					1371:1381	utilization	1371:1381	utilization by each fucosyltransferase	1371:1408	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	10	65	theme	fucosylated	1229:1239	arg1	glycans					1241:1247	fucosylated glycans	1229:1247	fucosylated glycans	1229:1247	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	8	66	theme	in	878:879	arg1	assays					906:911	Comprehensive in vitro fucosyltransferase assays	864:911	Comprehensive in vitro fucosyltransferase assays	864:911	Comprehensive in vitro fucosyltransferase assays revealed that 7-Alk-Fuc is commonly tolerated by most fucosyltransferases.
32825463	10	67	with	labeling	1203:1210	arg1	analogs					1258:1264	Fuc analogs	1254:1264	Fuc analogs	1254:1264	These findings demonstrate that labeling and detection of fucosylated glycans with Fuc analogs depend on multiple cellular steps, including conversion to GDP form, transport into the ER or Golgi, and utilization by each fucosyltransferase, providing insights into design of novel sugar analogs for specific detection of target glycans or inhibition of their functions.
32825463	9	68	theme	O-fucosyltransferases	1015:1035	arg1	POFUTs					1038:1043	both protein O-fucosyltransferases (POFUTs)	1002:1044	both protein O-fucosyltransferases (POFUTs)	1002:1044	Surprisingly, both protein O-fucosyltransferases (POFUTs) could transfer all Fuc analogs in vitro, likely because POFUT structures have a larger space around their Fuc binding sites.
32825463	8	69	theme	Comprehensive	864:876	arg1	assays					906:911	Comprehensive in vitro fucosyltransferase assays	864:911	Comprehensive in vitro fucosyltransferase assays	864:911	Comprehensive in vitro fucosyltransferase assays revealed that 7-Alk-Fuc is commonly tolerated by most fucosyltransferases.
32171833	7	0	theme	Composition	1083:1093	arg1	analysis					1095:1102	Composition analysis	1083:1102	Composition analysis	1083:1102	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	3	1	from	effects	388:394	arg1	levels					489:494	serum insulin levels	475:494	serum insulin levels (HOMA-IR)	475:504	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	1	from	effects	388:394	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	1	from	effects	388:394	arg1	protein					460:466	glycosylated serum protein	441:466	glycosylated serum protein (GSP)	441:472	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	1	from	effects	388:394	arg1	lipids					513:518	blood lipids	507:518	blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c))	507:667	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	1	from	effects	388:394	arg1	glucose					426:432	fasting blood glucose	412:432	fasting blood glucose (FBG)	412:438	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	8	2	theme	higher	1399:1404	arg1	content					1406:1412	its higher content	1395:1412	its higher content	1395:1412	Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.
32171833	7	3	theme	phenolic	1227:1234	arg1	content					1236:1242	total phenolic content	1221:1242	total phenolic content	1221:1242	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	0	4	from	study	12:16	arg1	function					34:41	antidiabetic function	21:41	antidiabetic function of six legume crude polysaccharides	21:77	Comparative study on antidiabetic function of six legume crude polysaccharides.
32171833	1	5	theme	white	161:165	arg1	soybean					209:215	small black soybean	197:215	small black soybean	197:215	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	5	theme	white	161:165	arg1	soybean					152:158	soybean	152:158	soybean	152:158	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	5	theme	white	161:165	arg1	bean					191:194	red kidney bean	180:194	red kidney bean	180:194	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	5	theme	white	161:165	arg1	bean					224:227	field bean	218:227	field bean	218:227	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	5	theme	white	161:165	arg1	lentil					230:235	lentil	230:235	lentil	230:235	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	5	theme	white	161:165	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	2	6	from	function	292:299	arg1	diet					313:316	high-fat diet	304:316	high-fat diet	304:316	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared.
32171833	2	6	from	function	292:299	arg1	mice					362:365	streptozotocin-induced type II diabetic mice	322:365	streptozotocin-induced type II diabetic mice	322:365	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared.
32171833	5	7	theme	legume	987:992	arg1	polysaccharides					994:1008	other legume polysaccharides	981:1008	other legume polysaccharides	981:1008	RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides.
32171833	2	8	theme	streptozotocin-induced	322:343	arg1	mice					362:365	streptozotocin-induced type II diabetic mice	322:365	streptozotocin-induced type II diabetic mice	322:365	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared.
32171833	2	9	theme	legume	255:260	arg1	polysaccharides					262:276	Six legume polysaccharides'	251:277	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice	251:365	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared.
32171833	7	10	from	composition	1312:1322	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	10	from	composition	1312:1322	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	6	11	theme	chemical	1015:1022	arg1	composition					1024:1034	The chemical composition	1011:1034	The chemical composition of six legume polysaccharides	1011:1064	The chemical composition of six legume polysaccharides were determined.
32171833	3	12	theme	high-density	623:634	arg1	cholesterol					648:658	high-density lipoprotein cholesterol	623:658	high-density lipoprotein cholesterol	623:658	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	4	13	theme	HOMA-IR	877:883	arg1	concentration					853:865	the concentration	849:865	the concentration of TG and HOMA-IR (p < 0.05)	849:894	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	1	14	dep	legumes	143:149	arg1	soybean					152:158	soybean	152:158	soybean	152:158	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	14	dep	legumes	143:149	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	7	15	from	acid	1215:1218	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	15	from	acid	1215:1218	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	16	theme	amino	1270:1274	arg1	composition					1281:1291	amino acid composition	1270:1291	amino acid composition	1270:1291	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	3	17	theme	lipoprotein	636:646	arg1	cholesterol					648:658	high-density lipoprotein cholesterol	623:658	high-density lipoprotein cholesterol	623:658	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	7	18	theme	flavonoid	1251:1259	arg1	content					1261:1267	total flavonoid content	1245:1267	total flavonoid content	1245:1267	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	8	19	theme	antidiabetic	1352:1363	arg1	activities					1365:1374	the antidiabetic activities	1348:1374	the antidiabetic activities of RK	1348:1380	Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.
32171833	3	20	theme	serum	475:479	arg1	levels					489:494	serum insulin levels	475:494	serum insulin levels (HOMA-IR)	475:504	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	20	theme	serum	475:479	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	20	theme	serum	475:479	arg1	HOMA-IR					497:503	HOMA-IR	497:503	HOMA-IR	497:503	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	1	21	theme	kidney	167:172	arg1	soybean					209:215	small black soybean	197:215	small black soybean	197:215	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	21	theme	kidney	167:172	arg1	soybean					152:158	soybean	152:158	soybean	152:158	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	21	theme	kidney	167:172	arg1	bean					191:194	red kidney bean	180:194	red kidney bean	180:194	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	21	theme	kidney	167:172	arg1	bean					224:227	field bean	218:227	field bean	218:227	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	21	theme	kidney	167:172	arg1	lentil					230:235	lentil	230:235	lentil	230:235	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	21	theme	kidney	167:172	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	3	22	theme	insulin	481:487	arg1	levels					489:494	serum insulin levels	475:494	serum insulin levels (HOMA-IR)	475:504	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	22	theme	insulin	481:487	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	22	theme	insulin	481:487	arg1	HOMA-IR					497:503	HOMA-IR	497:503	HOMA-IR	497:503	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	23	theme	blood	420:424	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	23	theme	blood	420:424	arg1	FBG					435:437	FBG	435:437	FBG	435:437	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	23	theme	blood	420:424	arg1	glucose					426:432	fasting blood glucose	412:432	fasting blood glucose (FBG)	412:438	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	1	24	theme	antidiabetic	84:95	arg1	function					97:104	The antidiabetic function	80:104	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil	80:235	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	5	25	theme	diabetic	952:959	arg1	mice					961:964	type II diabetic mice	944:964	type II diabetic mice	944:964	RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides.
32171833	7	26	theme	neutral	1193:1199	arg1	sugar					1201:1205	neutral sugar	1193:1205	neutral sugar	1193:1205	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	0	27	theme	Comparative	0:10	arg1	study					12:16	Comparative study	0:16	Comparative study on antidiabetic function of six legume crude polysaccharides	0:77	Comparative study on antidiabetic function of six legume crude polysaccharides.
32171833	7	28	theme	monosaccharide	1297:1310	arg1	composition					1312:1322	monosaccharide composition	1297:1322	monosaccharide composition	1297:1322	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	sugar					1201:1205	neutral sugar	1193:1205	neutral sugar	1193:1205	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	content					1236:1242	total phenolic content	1221:1242	total phenolic content	1221:1242	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	moisture					1178:1185	moisture	1178:1185	moisture	1178:1185	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	composition					1281:1291	amino acid composition	1270:1291	amino acid composition	1270:1291	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	ash					1188:1190	ash	1188:1190	ash	1188:1190	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	acid					1215:1218	uronic acid	1208:1218	uronic acid	1208:1218	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	composition					1312:1322	monosaccharide composition	1297:1322	monosaccharide composition	1297:1322	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	29	from	different	1165:1173	arg1	content					1261:1267	total flavonoid content	1245:1267	total flavonoid content	1245:1267	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	2	30	theme	antidiabetic	279:290	arg1	function					292:299	Six legume polysaccharides' antidiabetic function	251:299	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice	251:365	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared.
32171833	5	31	theme	other	981:985	arg1	polysaccharides					994:1008	other legume polysaccharides	981:1008	other legume polysaccharides	981:1008	RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides.
32171833	1	32	theme	red	180:182	arg1	bean					191:194	red kidney bean	180:194	red kidney bean	180:194	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	32	theme	red	180:182	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	0	33	theme	antidiabetic	21:32	arg1	function					34:41	antidiabetic function	21:41	antidiabetic function of six legume crude polysaccharides	21:77	Comparative study on antidiabetic function of six legume crude polysaccharides.
32171833	7	34	theme	acid	1276:1279	arg1	composition					1281:1291	amino acid composition	1270:1291	amino acid composition	1270:1291	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	4	35	theme	FBG	807:809	arg1	levels					797:802	the levels	793:802	the levels of FBG, GSP, TC, LDL-c	793:825	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	3	36	dep	lipids	513:518	arg1	including					521:529	including	521:529	including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)	521:666	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	37	gly	glycosylated	441:452	arg1	GSP					469:471	GSP	469:471	GSP	469:471	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	37	gly	glycosylated	441:452	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	37	gly	glycosylated	441:452	arg1	protein					460:466	glycosylated serum protein	441:466	glycosylated serum protein (GSP)	441:472	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	7	38	theme	total	1245:1249	arg1	content					1261:1267	total flavonoid content	1245:1267	total flavonoid content	1245:1267	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	1	39	theme	kidney	184:189	arg1	bean					191:194	red kidney bean	180:194	red kidney bean	180:194	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	39	theme	kidney	184:189	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	3	40	theme	blood	507:511	arg1	lipids					513:518	blood lipids	507:518	blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c))	507:667	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	40	theme	blood	507:511	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	8	41	theme	polysaccharide	1440:1453	arg1	content					1406:1412	its higher content	1395:1412	its higher content	1395:1412	Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.
32171833	8	41	theme	polysaccharide	1440:1453	arg1	structure					1427:1435	specific structure	1418:1435	specific structure	1418:1435	Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.
32171833	5	42	theme	antidiabetic	918:929	arg1	potential					931:939	greater antidiabetic potential	910:939	greater antidiabetic potential	910:939	RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides.
32171833	1	43	theme	polysaccharides	109:123	arg1	function					97:104	The antidiabetic function	80:104	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil	80:235	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	7	44	theme	legume	1127:1132	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	44	theme	legume	1127:1132	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	4	45	theme	bean	713:716	arg1	RK					735:736	RK	735:736	RK	735:736	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	4	45	theme	bean	713:716	arg1	polysaccharides					718:732	red kidney bean polysaccharides	702:732	red kidney bean polysaccharides (RK)	702:737	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	8	46	theme	specific	1418:1425	arg1	structure					1427:1435	specific structure	1418:1435	specific structure	1418:1435	Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.
32171833	3	47	theme	body	399:402	arg1	levels					489:494	serum insulin levels	475:494	serum insulin levels (HOMA-IR)	475:504	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	47	theme	body	399:402	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	47	theme	body	399:402	arg1	protein					460:466	glycosylated serum protein	441:466	glycosylated serum protein (GSP)	441:472	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	47	theme	body	399:402	arg1	lipids					513:518	blood lipids	507:518	blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c))	507:667	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	47	theme	body	399:402	arg1	glucose					426:432	fasting blood glucose	412:432	fasting blood glucose (FBG)	412:438	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	48	theme	total	531:535	arg1	HDL-c					661:665	HDL-c	661:665	HDL-c	661:665	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	48	theme	total	531:535	arg1	TC					550:551	TC	550:551	TC	550:551	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	48	theme	total	531:535	arg1	cholesterol					537:547	total cholesterol	531:547	total cholesterol (TC)	531:552	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	7	49	from	moisture	1178:1185	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	49	from	moisture	1178:1185	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	1	50	theme	small	197:201	arg1	soybean					209:215	small black soybean	197:215	small black soybean	197:215	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	50	theme	small	197:201	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	0	51	theme	legume	50:55	arg1	polysaccharides					63:77	six legume crude polysaccharides	46:77	six legume crude polysaccharides	46:77	Comparative study on antidiabetic function of six legume crude polysaccharides.
32171833	3	52	theme	fasting	412:418	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	52	theme	fasting	412:418	arg1	FBG					435:437	FBG	435:437	FBG	435:437	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	52	theme	fasting	412:418	arg1	glucose					426:432	fasting blood glucose	412:432	fasting blood glucose (FBG)	412:438	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	8	53	theme	RK	1379:1380	arg1	activities					1365:1374	the antidiabetic activities	1348:1374	the antidiabetic activities of RK	1348:1380	Results indicated that the antidiabetic activities of RK might due to its higher content and specific structure of polysaccharide.
32171833	3	54	theme	serum	454:458	arg1	GSP					469:471	GSP	469:471	GSP	469:471	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	54	theme	serum	454:458	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	54	theme	serum	454:458	arg1	protein					460:466	glycosylated serum protein	441:466	glycosylated serum protein (GSP)	441:472	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	4	55	theme	TG	870:871	arg1	concentration					853:865	the concentration	849:865	the concentration of TG and HOMA-IR (p < 0.05)	849:894	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	3	56	theme	low-density	574:584	arg1	LDL-c					611:615	LDL-c	611:615	LDL-c	611:615	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	56	theme	low-density	574:584	arg1	cholesterol					598:608	low-density lipoprotein cholesterol	574:608	low-density lipoprotein cholesterol (LDL-c)	574:616	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	7	57	from	ash	1188:1190	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	57	from	ash	1188:1190	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	4	58	theme	emaciation	771:780	arg1	symptoms					759:766	the symptoms	755:766	the symptoms of emaciation	755:780	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	7	59	from	content	1261:1267	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	59	from	content	1261:1267	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	3	60	theme	lipoprotein	586:596	arg1	LDL-c					611:615	LDL-c	611:615	LDL-c	611:615	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	60	theme	lipoprotein	586:596	arg1	cholesterol					598:608	low-density lipoprotein cholesterol	574:608	low-density lipoprotein cholesterol (LDL-c)	574:616	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	7	61	theme	total	1221:1225	arg1	content					1236:1242	total phenolic content	1221:1242	total phenolic content	1221:1242	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	4	62	theme	kidney	706:711	arg1	RK					735:736	RK	735:736	RK	735:736	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	4	62	theme	kidney	706:711	arg1	polysaccharides					718:732	red kidney bean polysaccharides	702:732	red kidney bean polysaccharides (RK)	702:737	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	2	63	theme	high-fat	304:311	arg1	diet					313:316	high-fat diet	304:316	high-fat diet	304:316	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared.
32171833	1	64	theme	black	203:207	arg1	soybean					209:215	small black soybean	197:215	small black soybean	197:215	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	64	theme	black	203:207	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	7	65	from	content	1236:1242	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	65	from	content	1236:1242	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	6	66	theme	legume	1043:1048	arg1	polysaccharides					1050:1064	six legume polysaccharides	1039:1064	six legume polysaccharides	1039:1064	The chemical composition of six legume polysaccharides were determined.
32171833	3	67	theme	glycosylated	441:452	arg1	GSP					469:471	GSP	469:471	GSP	469:471	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	67	theme	glycosylated	441:452	arg1	weight					404:409	body weight	399:409	body weight	399:409	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	3	67	theme	glycosylated	441:452	arg1	protein					460:466	glycosylated serum protein	441:466	glycosylated serum protein (GSP)	441:472	Their effects on body weight, fasting blood glucose (FBG), glycosylated serum protein (GSP), serum insulin levels (HOMA-IR), blood lipids (including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) were tested.
32171833	0	68	theme	polysaccharides	63:77	arg1	function					34:41	antidiabetic function	21:41	antidiabetic function of six legume crude polysaccharides	21:77	Comparative study on antidiabetic function of six legume crude polysaccharides.
32171833	5	69	theme	greater	910:916	arg1	potential					931:939	greater antidiabetic potential	910:939	greater antidiabetic potential	910:939	RK exhibited greater antidiabetic potential in type II diabetic mice, compared with other legume polysaccharides.
32171833	4	70	theme	red	702:704	arg1	RK					735:736	RK	735:736	RK	735:736	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	4	70	theme	red	702:704	arg1	polysaccharides					718:732	red kidney bean polysaccharides	702:732	red kidney bean polysaccharides (RK)	702:737	Results showed that red kidney bean polysaccharides (RK) could alleviate the symptoms of emaciation, decreased the levels of FBG, GSP, TC, LDL-c and obviously reduced the concentration of TG and HOMA-IR (p < 0.05).
32171833	7	71	from	sugar	1201:1205	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	71	from	sugar	1201:1205	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	2	72	theme	diabetic	353:360	arg1	mice					362:365	streptozotocin-induced type II diabetic mice	322:365	streptozotocin-induced type II diabetic mice	322:365	Six legume polysaccharides' antidiabetic function in high-fat diet and streptozotocin-induced type II diabetic mice were compared.
32171833	7	73	theme	uronic	1208:1213	arg1	acid					1215:1218	uronic acid	1208:1218	uronic acid	1208:1218	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	0	74	theme	crude	57:61	arg1	polysaccharides					63:77	six legume crude polysaccharides	46:77	six legume crude polysaccharides	46:77	Comparative study on antidiabetic function of six legume crude polysaccharides.
32171833	6	75	theme	polysaccharides	1050:1064	arg1	composition					1024:1034	The chemical composition	1011:1034	The chemical composition of six legume polysaccharides	1011:1064	The chemical composition of six legume polysaccharides were determined.
32171833	7	76	from	composition	1281:1291	arg1	polysaccharides					1134:1148	the six legume polysaccharides	1119:1148	the six legume polysaccharides	1119:1148	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	7	76	from	composition	1281:1291	arg1	different					1165:1173	different	1165:1173	different	1165:1173	Composition analysis indicated that the six legume polysaccharides were obviously different in moisture, ash, neutral sugar, uronic acid, total phenolic content, total flavonoid content, amino acid composition and monosaccharide composition.
32171833	1	77	theme	field	218:222	arg1	bean					174:177	white kidney bean	161:177	white kidney bean	161:177	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32171833	1	77	theme	field	218:222	arg1	bean					224:227	field bean	218:227	field bean	218:227	The antidiabetic function of polysaccharides prepared from six legumes: soybean, white kidney bean, red kidney bean, small black soybean, field bean, lentil were studied.
32374435	2	0	theme	glycosyltransferases	511:530	arg1	multitude					487:495	the multitude	483:495	the multitude of endogenous glycosyltransferases	483:530	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	8	1	theme	further	1672:1678	arg1	innovation					1680:1689	further innovation	1672:1689	further innovation	1672:1689	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	8	2	theme	biology	1634:1640	arg1	challenge					1642:1650	an incompletely solved synthetic biology challenge	1601:1650	an incompletely solved synthetic biology challenge	1601:1650	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	8	2	theme	biology	1634:1640	arg1	robustly					1484:1491	robustly	1484:1491	robustly	1484:1491	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	1	3	theme	expression	169:178	arg1	hosts					180:184	several eukaryotic protein expression hosts	142:184	several eukaryotic protein expression hosts	142:184	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	1	4	theme	application-customized	276:297	arg1	structures					306:315	humanized application-customized glycan structures	266:315	humanized application-customized glycan structures	266:315	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	2	5	theme	endogenous	500:509	arg1	glycosyltransferases					511:530	endogenous glycosyltransferases	500:530	endogenous glycosyltransferases	500:530	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	7	6	with	modification	1373:1384	arg1	structure					1423:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	1	7	gly	glycoproteins	247:259	arg1	glycoproteins					247:259	therapeutic glycoproteins	235:259	therapeutic glycoproteins	235:259	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	1	8	theme	hosts	180:184	arg1	pathways					130:137	The glycosylation pathways	112:137	The glycosylation pathways of several eukaryotic protein expression hosts	112:184	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	6	9	theme	magnetic	1091:1098	arg1	resonance					1100:1108	nuclear magnetic resonance	1083:1108	nuclear magnetic resonance	1083:1108	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	1	10	theme	glycan	299:304	arg1	structures					306:315	humanized application-customized glycan structures	266:315	humanized application-customized glycan structures	266:315	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	5	11	theme	GlycoSwitchM5	774:786	arg1	strain					788:793	Komagataella phaffii) GlycoSwitchM5 strain	752:793	Komagataella phaffii) GlycoSwitchM5 strain	752:793	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	6	12	theme	linkage	1061:1067	arg1	analysis					1069:1076	linkage analysis	1061:1076	linkage analysis	1061:1076	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	0	13	theme	Pichia	95:100	arg1	pastoris					102:109	Pichia pastoris	95:109	Pichia pastoris	95:109	Off-target glycans encountered along the synthetic biology route toward humanized N-glycans in Pichia pastoris.
32374435	8	14	theme	glycoprotein	1706:1717	arg1	production					1734:1743	safe glycoprotein pharmaceutical production	1701:1743	safe glycoprotein pharmaceutical production	1701:1743	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	2	15	theme	expression	329:338	arg1	hosts					340:344	several expression hosts	321:344	several expression hosts	321:344	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	7	16	theme	GlcNAcMan5	1404:1413	arg1	structure					1423:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	7	17	theme	GlcNAc2	1415:1421	arg1	structure					1423:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	2	18	theme	several	321:327	arg1	hosts					340:344	several expression hosts	321:344	several expression hosts	321:344	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	5	19	theme	Man5	901:904	arg1	species					892:898	two major species	882:898	two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure	882:975	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	5	19	theme	Man5	901:904	arg1	GlcNAc2					906:912	Man5 GlcNAc2	901:912	Man5 GlcNAc2	901:912	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	2	20	theme	heterologous	540:551	arg1	background					553:562	such heterologous background	535:562	such heterologous background	535:562	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	7	21	theme	GlcNAc	1261:1266	arg1	transferase-I					1268:1280	a Golgi-targeted GlcNAc transferase-I	1244:1280	a Golgi-targeted GlcNAc transferase-I	1244:1280	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	7	22	theme	novel	1323:1327	arg1	modification					1329:1340	this novel modification	1318:1340	this novel modification	1318:1340	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	5	23	theme	glycan	856:861	arg1	profiling					863:871	glycan profiling	856:871	glycan profiling	856:871	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	8	24	theme	particular	1559:1568	arg1	structures					1581:1590	particular human-type structures	1559:1590	particular human-type structures	1559:1590	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	2	25	theme	N-glycan	410:417	arg1	structures					419:428	the new N-glycan structures	402:428	the new N-glycan structures	402:428	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	2	25	theme	N-glycan	410:417	arg1	substrates					453:462	substrates	453:462	substrates for one or more of the multitude of endogenous glycosyltransferases	453:530	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	3	26	dep	novel	603:607	arg1	undesired					610:618	undesired	610:618	undesired	610:618	This then results in the formation of novel, undesired glycan structures, which often remain insufficiently characterized.
32374435	8	27	theme	pharmaceutical	1719:1732	arg1	production					1734:1743	safe glycoprotein pharmaceutical production	1701:1743	safe glycoprotein pharmaceutical production	1701:1743	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	2	28	theme	such	535:538	arg1	background					553:562	such heterologous background	535:562	such heterologous background	535:562	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	3	29	theme	novel	603:607	arg1	structures					627:636	novel, undesired glycan structures	603:636	novel, undesired glycan structures	603:636	This then results in the formation of novel, undesired glycan structures, which often remain insufficiently characterized.
32374435	8	30	theme	safe	1701:1704	arg1	production					1734:1743	safe glycoprotein pharmaceutical production	1701:1743	safe glycoprotein pharmaceutical production	1701:1743	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	2	31	theme	new	406:408	arg1	structures					419:428	the new N-glycan structures	402:428	the new N-glycan structures	402:428	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	2	31	theme	new	406:408	arg1	substrates					453:462	substrates	453:462	substrates for one or more of the multitude of endogenous glycosyltransferases	453:530	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	0	32	theme	Off-target	0:9	arg1	glycans					11:17	Off-target glycans	0:17	Off-target glycans	0:17	Off-target glycans encountered along the synthetic biology route toward humanized N-glycans in Pichia pastoris.
32374435	7	33	theme	transferase-I	1268:1280	arg1	Expression					1230:1239	Expression	1230:1239	Expression of a Golgi-targeted GlcNAc transferase-I	1230:1280	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	6	34	mod	modified	1159:1166	arg3	tetrasaccharide					1213:1227	a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide	1173:1227	a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide	1173:1227	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	6	34	mod	modified	1159:1166	arg1	glycan					1135:1140	this novel glycan	1124:1140	this novel glycan	1124:1140	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	8	35	theme	solved	1617:1622	arg1	challenge					1642:1650	an incompletely solved synthetic biology challenge	1601:1650	an incompletely solved synthetic biology challenge	1601:1650	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	8	35	theme	solved	1617:1622	arg1	robustly					1484:1491	robustly	1484:1491	robustly	1484:1491	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	6	36	theme	Man5	1146:1149	arg1	GlcNAc2					1151:1157	Man5 GlcNAc2	1146:1157	Man5 GlcNAc2	1146:1157	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	1	37	with	production	221:230	arg1	structures					306:315	humanized application-customized glycan structures	266:315	humanized application-customized glycan structures	266:315	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	8	38	theme	human-type	1570:1579	arg1	structures					1581:1590	particular human-type structures	1559:1590	particular human-type structures	1559:1590	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	5	39	dep	unexpected	921:930	arg1	α-mannosidase-resistant					943:965	α-mannosidase-resistant	943:965	α-mannosidase-resistant	943:965	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	2	40	from	successful	367:376	arg1	hosts					340:344	several expression hosts	321:344	several expression hosts	321:344	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	6	41	theme	novel	1129:1133	arg1	glycan					1135:1140	this novel glycan	1124:1140	this novel glycan	1124:1140	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	8	42	gly	glycoprotein	1706:1717	arg1	glycoprotein					1706:1717	safe glycoprotein pharmaceutical production	1701:1743	safe glycoprotein pharmaceutical production	1701:1743	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	8	43	dep	robustly	1484:1491	arg1	customizing					1493:1503	customizing	1493:1503	customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures	1493:1590	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	5	44	theme	Komagataella	752:763	arg1	strain					788:793	Komagataella phaffii) GlycoSwitchM5 strain	752:793	Komagataella phaffii) GlycoSwitchM5 strain	752:793	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	8	45	theme	synthetic	1624:1632	arg1	challenge					1642:1650	an incompletely solved synthetic biology challenge	1601:1650	an incompletely solved synthetic biology challenge	1601:1650	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	8	45	theme	synthetic	1624:1632	arg1	robustly					1484:1491	robustly	1484:1491	robustly	1484:1491	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	5	46	theme	major	886:890	arg1	species					892:898	two major species	882:898	two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure	882:975	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	5	46	theme	major	886:890	arg1	GlcNAc2					906:912	Man5 GlcNAc2	901:912	Man5 GlcNAc2	901:912	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	5	46	theme	major	886:890	arg1	structure					967:975	an unexpected, partially α-mannosidase-resistant structure	918:975	an unexpected, partially α-mannosidase-resistant structure	918:975	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	0	47	theme	synthetic	41:49	arg1	route					59:63	the synthetic biology route	37:63	the synthetic biology route toward humanized N-glycans in Pichia pastoris	37:109	Off-target glycans encountered along the synthetic biology route toward humanized N-glycans in Pichia pastoris.
32374435	5	48	theme	phaffii	765:771	arg1	strain					788:793	Komagataella phaffii) GlycoSwitchM5 strain	752:793	Komagataella phaffii) GlycoSwitchM5 strain	752:793	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	0	49	from	N-glycans	82:90	arg1	pastoris					102:109	Pichia pastoris	95:109	Pichia pastoris	95:109	Off-target glycans encountered along the synthetic biology route toward humanized N-glycans in Pichia pastoris.
32374435	3	50	theme	structures	627:636	arg1	formation					590:598	the formation	586:598	the formation of novel, undesired glycan structures, which often remain insufficiently characterized	586:685	This then results in the formation of novel, undesired glycan structures, which often remain insufficiently characterized.
32374435	2	51	theme	multitude	487:495	arg1	multitude					487:495	the multitude	483:495	the multitude of endogenous glycosyltransferases	483:530	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	2	51	theme	multitude	487:495	arg1	one					468:470	one	468:470	one	468:470	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	6	52	theme	exoglycosidase	1015:1028	arg1	sequencing					1030:1039	exoglycosidase sequencing	1015:1039	exoglycosidase sequencing	1015:1039	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	5	53	theme	Man5	832:835	arg1	N-glycans					845:853	Man5 GlcNAc2 N-glycans	832:853	Man5 GlcNAc2 N-glycans	832:853	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	4	54	dep	expressing	693:702	arg1	syn					747:749	syn	747:749	syn	747:749	When expressing mouse interleukin-22 in a Pichia pastoris (syn.
32374435	6	55	dep	modified	1159:1166	arg1	GlcNAc2					1151:1157	Man5 GlcNAc2	1146:1157	Man5 GlcNAc2	1146:1157	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	8	56	theme	accumulating	1457:1468	arg1	evidence					1470:1477	accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production	1457:1743	accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production	1457:1743	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	5	57	theme	GlcNAc2	837:843	arg1	N-glycans					845:853	Man5 GlcNAc2 N-glycans	832:853	Man5 GlcNAc2 N-glycans	832:853	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	5	58	theme	unexpected	921:930	arg1	species					892:898	two major species	882:898	two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure	882:975	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	5	58	theme	unexpected	921:930	arg1	structure					967:975	an unexpected, partially α-mannosidase-resistant structure	918:975	an unexpected, partially α-mannosidase-resistant structure	918:975	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	6	59	theme	mass	1042:1045	arg1	spectrometry					1047:1058	mass spectrometry	1042:1058	mass spectrometry	1042:1058	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	6	60	theme	Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R	1175:1211	arg1	tetrasaccharide					1213:1227	a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide	1173:1227	a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide	1173:1227	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	1	61	theme	glycosylation	116:128	arg1	pathways					130:137	The glycosylation pathways	112:137	The glycosylation pathways of several eukaryotic protein expression hosts	112:184	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	0	62	theme	biology	51:57	arg1	route					59:63	the synthetic biology route	37:63	the synthetic biology route toward humanized N-glycans in Pichia pastoris	37:109	Off-target glycans encountered along the synthetic biology route toward humanized N-glycans in Pichia pastoris.
32374435	3	63	theme	glycan	620:625	arg1	structures					627:636	novel, undesired glycan structures	603:636	novel, undesired glycan structures	603:636	This then results in the formation of novel, undesired glycan structures, which often remain insufficiently characterized.
32374435	7	64	theme	modification	1329:1340	arg1	formation					1305:1313	the formation	1301:1313	the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure	1301:1431	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	8	65	from	pathway	1525:1531	arg1	pastoris					1539:1546	P. pastoris	1536:1546	P. pastoris	1536:1546	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	6	66	theme	structural	989:998	arg1	analysis					1000:1007	A detailed structural analysis	978:1007	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance	978:1108	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	7	67	theme	Golgi-targeted	1246:1259	arg1	transferase-I					1268:1280	a Golgi-targeted GlcNAc transferase-I	1244:1280	a Golgi-targeted GlcNAc transferase-I	1244:1280	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	5	68	dep	species	892:898	arg1	species					892:898	two major species	882:898	two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure	882:975	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	5	68	dep	species	892:898	arg1	GlcNAc2					906:912	Man5 GlcNAc2	901:912	Man5 GlcNAc2	901:912	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	5	68	dep	species	892:898	arg1	structure					967:975	an unexpected, partially α-mannosidase-resistant structure	918:975	an unexpected, partially α-mannosidase-resistant structure	918:975	Komagataella phaffii) GlycoSwitchM5 strain, which had been optimized to produce Man5 GlcNAc2 N-glycans, glycan profiling revealed two major species: Man5 GlcNAc2 and an unexpected, partially α-mannosidase-resistant structure.
32374435	4	69	theme	Pichia	730:735	arg1	pastoris					737:744	a Pichia pastoris	728:744	a Pichia pastoris	728:744	When expressing mouse interleukin-22 in a Pichia pastoris (syn.
32374435	7	70	theme	targeted	1395:1402	arg1	structure					1423:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	the targeted GlcNAcMan5 GlcNAc2 structure	1391:1431	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	1	71	theme	therapeutic	235:245	arg1	glycoproteins					247:259	therapeutic glycoproteins	235:259	therapeutic glycoproteins	235:259	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	8	72	theme	N-glycosylation	1509:1523	arg1	pathway					1525:1531	the N-glycosylation pathway	1505:1531	the N-glycosylation pathway in P. pastoris to produce particular human-type structures	1505:1590	Our findings reinforce accumulating evidence that robustly customizing the N-glycosylation pathway in P. pastoris to produce particular human-type structures is still an incompletely solved synthetic biology challenge, which will require further innovation to enable safe glycoprotein pharmaceutical production.
32374435	1	73	theme	several	142:148	arg1	hosts					180:184	several eukaryotic protein expression hosts	142:184	several eukaryotic protein expression hosts	142:184	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	2	74	from	hosts	340:344	arg1	successful					367:376	successful	367:376	successful	367:376	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	1	75	theme	glycoproteins	247:259	arg1	production					221:230	the production	217:230	the production of therapeutic glycoproteins with humanized application-customized glycan structures	217:315	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	0	76	theme	humanized	72:80	arg1	N-glycans					82:90	humanized N-glycans	72:90	humanized N-glycans in Pichia pastoris	72:109	Off-target glycans encountered along the synthetic biology route toward humanized N-glycans in Pichia pastoris.
32374435	1	77	theme	eukaryotic	150:159	arg1	hosts					180:184	several eukaryotic protein expression hosts	142:184	several eukaryotic protein expression hosts	142:184	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	4	78	theme	mouse	704:708	arg1	interleukin-22					710:723	mouse interleukin-22	704:723	mouse interleukin-22	704:723	When expressing mouse interleukin-22 in a Pichia pastoris (syn.
32374435	6	79	theme	nuclear	1083:1089	arg1	resonance					1100:1108	nuclear magnetic resonance	1083:1108	nuclear magnetic resonance	1083:1108	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	6	80	theme	detailed	980:987	arg1	analysis					1000:1007	A detailed structural analysis	978:1007	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance	978:1108	A detailed structural analysis using exoglycosidase sequencing, mass spectrometry, linkage analysis, and nuclear magnetic resonance revealed that this novel glycan was Man5 GlcNAc2 modified with a Glcα-1,2-Manβ-1,2-Manβ-1,3-Glcα-1,3-R tetrasaccharide.
32374435	2	81	from	substrates	453:462	arg1	background					553:562	such heterologous background	535:562	such heterologous background	535:562	In several expression hosts, this has been quite successful, but one caveat is that the new N-glycan structures inadvertently might be substrates for one or more of the multitude of endogenous glycosyltransferases in such heterologous background.
32374435	1	82	theme	protein	161:167	arg1	hosts					180:184	several eukaryotic protein expression hosts	142:184	several eukaryotic protein expression hosts	142:184	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32374435	7	83	theme	homogeneous	1361:1371	arg1	modification					1373:1384	more homogeneous modification	1356:1384	more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure	1356:1431	Expression of a Golgi-targeted GlcNAc transferase-I strongly inhibited the formation of this novel modification, resulting in more homogeneous modification with the targeted GlcNAcMan5 GlcNAc2 structure.
32374435	1	84	theme	humanized	266:274	arg1	structures					306:315	humanized application-customized glycan structures	266:315	humanized application-customized glycan structures	266:315	The glycosylation pathways of several eukaryotic protein expression hosts are being engineered to enable the production of therapeutic glycoproteins with humanized application-customized glycan structures.
32858085	2	0	theme	client	433:438	arg1	glycoproteins					440:452	client glycoproteins	433:452	client glycoproteins	433:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	11	1	dep	play	1615:1618	arg1	sensing					1639:1645	sensing	1639:1645	sensing the misfolded glycoprotein	1639:1672	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	11	1	dep	play	1615:1618	arg1	promoting					1686:1694	promoting	1686:1694	promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control	1686:1777	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	4	2	theme	denatured	818:826	arg1	M9GN2-RNase					828:838	the denatured M9GN2-RNase	814:838	the denatured M9GN2-RNase	814:838	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	1	3	theme	glycoproteins	127:139	arg1	folding					116:122	folding	116:122	folding of glycoproteins	116:139	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	11	4	gly	glycoproteins	1707:1719	arg1	glycoproteins					1707:1719	glycoproteins	1707:1719	glycoproteins	1707:1719	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	6	5	theme	RESULTS	950:956	arg1	HUGT1					958:962	RESULTS HUGT1	950:962	RESULTS HUGT1	950:962	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	11	6	theme	glycoprotein	1750:1761	arg1	control					1771:1777	the endoplasmic reticulum glycoprotein quality control	1724:1777	the endoplasmic reticulum glycoprotein quality control	1724:1777	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	6	7	theme	same	1048:1051	arg1	extent					1053:1058	the same extent	1044:1058	the same extent	1044:1058	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	6	7	theme	same	1048:1051	arg1	folding					989:995	the folding	985:995	the folding of M9GN2-RNase and non-glycosylated RNase A	985:1039	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	4	8	theme	RNase	742:746	arg1	B					748:748	truncated RNase B	732:748	truncated RNase B	732:748	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	1	9	theme	functional	232:241	arg1	structures					243:252	biologically functional structures	219:252	biologically functional structures	219:252	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	2	10	theme	glycoprotein	283:294	arg1	glucosyltransferase					296:314	glycoprotein glucosyltransferase 1	283:316	UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1)	271:324	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	2	10	theme	glycoprotein	283:294	arg1	UGGT1					319:323	UGGT1	319:323	UGGT1	319:323	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	9	11	theme	HUGT1	1248:1252	arg1	mutant					1254:1259	an HUGT1 mutant	1245:1259	an HUGT1 mutant which lacks the glucosyltransferase activity	1245:1304	Additionally, an HUGT1 mutant which lacks the glucosyltransferase activity did not accelerate the protein folding of M9GN2-RNase.
32858085	4	12	theme	M9GN2-RNase	828:838	arg1	refolding					801:809	refolding	801:809	refolding of the denatured M9GN2-RNase	801:838	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	4	13	theme	truncated	732:740	arg1	B					748:748	truncated RNase B	732:748	truncated RNase B	732:748	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	11	14	theme	endoplasmic	1728:1738	arg1	reticulum					1740:1748	the endoplasmic reticulum	1724:1748	the endoplasmic reticulum glycoprotein quality control	1724:1777	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	6	15	theme	M9GN2-RNase	1000:1010	arg1	A					1039:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	3	16	theme	transferase	476:486	arg1	activity					488:495	its transferase activity	472:495	its transferase activity	472:495	However, besides its transferase activity, whether UGGT1 possesses any chaperone activity that facilitates protein folding is yet to be addressed.
32858085	6	17	theme	RNase	1033:1037	arg1	A					1039:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	7	18	theme	UDP-Glc	1145:1151	arg1	presence					1133:1140	the presence	1129:1140	the presence of UDP-Glc	1129:1151	However, HUGT1 remarkably accelerated the folding of M9GN2-RNase in the presence of UDP-Glc.
32858085	10	19	theme	protein	1432:1438	arg1	refolding					1409:1417	the refolding	1405:1417	the refolding of denatured protein	1405:1438	CONCLUSIONS HUGT1has the ability to promote the refolding of denatured protein and the effect would be enhanced when HUGT1 tightly interacts with the client protein via glycan recognition.
32858085	6	20	theme	A	1039:1039	arg1	extent					1053:1058	the same extent	1044:1058	the same extent	1044:1058	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	6	20	theme	A	1039:1039	arg1	folding					989:995	the folding	985:995	the folding of M9GN2-RNase and non-glycosylated RNase A	985:1039	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	2	21	theme	ability	391:397	arg1	virtue					377:382	virtue	377:382	virtue of its ability to discriminate folding states of client glycoproteins	377:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	8	22	from	contrast	1157:1164	arg1	effective					1195:1203	effective	1195:1203	effective	1195:1203	In contrast, neither UDP nor UDP-Gal was effective in enhancing the folding.
32858085	10	23	theme	denatured	1422:1430	arg1	protein					1432:1438	denatured protein	1422:1438	denatured protein	1422:1438	CONCLUSIONS HUGT1has the ability to promote the refolding of denatured protein and the effect would be enhanced when HUGT1 tightly interacts with the client protein via glycan recognition.
32858085	2	24	gly	glycoproteins	440:452	arg1	glycoproteins					440:452	client glycoproteins	433:452	client glycoproteins	433:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	11	25	gly	glycoprotein	1661:1672	arg1	glycoprotein					1661:1672	the misfolded glycoprotein	1647:1672	the misfolded glycoprotein	1647:1672	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	4	26	theme	glycan	640:645	arg1	M9GN2-RNase					663:673	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	11	27	theme	reticulum	1740:1748	arg1	control					1771:1777	the endoplasmic reticulum glycoprotein quality control	1724:1777	the endoplasmic reticulum glycoprotein quality control	1724:1777	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	3	28	contain	possesses	512:520	arg2	activity					536:543	any chaperone activity	522:543	any chaperone activity that facilitates protein folding	522:576	However, besides its transferase activity, whether UGGT1 possesses any chaperone activity that facilitates protein folding is yet to be addressed.
32858085	3	28	contain	possesses	512:520	arg1	UGGT1					506:510	UGGT1	506:510	UGGT1	506:510	However, besides its transferase activity, whether UGGT1 possesses any chaperone activity that facilitates protein folding is yet to be addressed.
32858085	3	29	theme	chaperone	526:534	arg1	activity					536:543	any chaperone activity	522:543	any chaperone activity that facilitates protein folding	522:576	However, besides its transferase activity, whether UGGT1 possesses any chaperone activity that facilitates protein folding is yet to be addressed.
32858085	1	30	theme	combined	158:165	arg1	action					167:172	a combined action	156:172	a combined action of enzymes and chaperones that leads them to biologically functional structures	156:252	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	7	31	theme	M9GN2-RNase	1114:1124	arg1	folding					1103:1109	the folding	1099:1109	the folding of M9GN2-RNase	1099:1124	However, HUGT1 remarkably accelerated the folding of M9GN2-RNase in the presence of UDP-Glc.
32858085	9	32	theme	glucosyltransferase	1277:1295	arg1	activity					1297:1304	the glucosyltransferase activity	1273:1304	the glucosyltransferase activity	1273:1304	Additionally, an HUGT1 mutant which lacks the glucosyltransferase activity did not accelerate the protein folding of M9GN2-RNase.
32858085	1	33	theme	endoplasmic	88:98	arg1	ER					111:112	ER	111:112	ER	111:112	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	1	33	theme	endoplasmic	88:98	arg1	reticulum					100:108	the endoplasmic reticulum	84:108	the endoplasmic reticulum (ER)	84:113	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	4	34	dep	METHODS	602:608	arg1	We					610:611	We	610:611	We	610:611	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	0	35	theme	refolding	17:25	arg1	activity					27:34	refolding activity	17:34	refolding activity of ER glucosyltransferase (UGGT)	17:67	Glycan dependent refolding activity of ER glucosyltransferase (UGGT).
32858085	11	36	theme	quality	1763:1769	arg1	control					1771:1777	the endoplasmic reticulum glycoprotein quality control	1724:1777	the endoplasmic reticulum glycoprotein quality control	1724:1777	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	11	37	theme	misfolded	1651:1659	arg1	glycoprotein					1661:1672	the misfolded glycoprotein	1647:1672	the misfolded glycoprotein	1647:1672	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	4	38	theme	RNase	656:660	arg1	M9GN2-RNase					663:673	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	0	39	theme	ER	39:40	arg1	UGGT					63:66	UGGT	63:66	UGGT	63:66	Glycan dependent refolding activity of ER glucosyltransferase (UGGT).
32858085	0	39	theme	ER	39:40	arg1	glucosyltransferase					42:60	ER glucosyltransferase	39:60	ER glucosyltransferase (UGGT)	39:67	Glycan dependent refolding activity of ER glucosyltransferase (UGGT).
32858085	1	40	theme	enzymes	177:183	arg1	action					167:172	a combined action	156:172	a combined action of enzymes and chaperones that leads them to biologically functional structures	156:252	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	4	41	theme	UGGT1	783:787	arg1	effect					767:772	the effect	763:772	the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase	763:838	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	4	42	theme	oligomannose-type	622:638	arg1	M9GN2-RNase					663:673	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	2	43	theme	sensor	366:371	arg1	role					345:348	an essential role	332:348	an essential role	332:348	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	2	43	theme	sensor	366:371	arg1	"					372:372	the "folding sensor"	353:372	the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins	353:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	2	44	theme	folding	415:421	arg1	states					423:428	folding states	415:428	folding states of client glycoproteins	415:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	3	45	theme	protein	562:568	arg1	folding					570:576	protein folding	562:576	protein folding	562:576	However, besides its transferase activity, whether UGGT1 possesses any chaperone activity that facilitates protein folding is yet to be addressed.
32858085	8	46	from	effective	1195:1203	arg1	contrast					1157:1164	contrast	1157:1164	contrast	1157:1164	In contrast, neither UDP nor UDP-Gal was effective in enhancing the folding.
32858085	2	47	theme	folding	358:364	arg1	role					345:348	an essential role	332:348	an essential role	332:348	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	2	47	theme	folding	358:364	arg1	"					372:372	the "folding sensor"	353:372	the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins	353:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	2	48	gly	glycoprotein	283:294	arg1	glycoprotein					283:294	glycoprotein glucosyltransferase 1	283:316	UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1)	271:324	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	11	49	theme	GENERAL	1550:1556	arg1	SIGNIFICANCE					1558:1569	GENERAL SIGNIFICANCE	1550:1569	GENERAL SIGNIFICANCE Our study	1550:1579	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	2	50	dep	UDP-glucose	271:281	arg1	glucosyltransferase					296:314	glycoprotein glucosyltransferase 1	283:316	UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1)	271:324	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	2	50	dep	UDP-glucose	271:281	arg1	UGGT1					319:323	UGGT1	319:323	UGGT1	319:323	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	0	51	theme	glucosyltransferase	42:60	arg1	activity					27:34	refolding activity	17:34	refolding activity of ER glucosyltransferase (UGGT)	17:67	Glycan dependent refolding activity of ER glucosyltransferase (UGGT).
32858085	6	52	theme	non-glycosylated	1016:1031	arg1	A					1039:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	11	53	theme	SIGNIFICANCE	1558:1569	arg1	study					1575:1579	GENERAL SIGNIFICANCE Our study	1550:1579	GENERAL SIGNIFICANCE Our study	1550:1579	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	1	54	dep	BACKGROUND	70:79	arg1	assisted					144:151	assisted	144:151	assisted	144:151	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	9	55	theme	protein	1329:1335	arg1	folding					1337:1343	the protein folding	1325:1343	the protein folding of M9GN2-RNase	1325:1358	Additionally, an HUGT1 mutant which lacks the glucosyltransferase activity did not accelerate the protein folding of M9GN2-RNase.
32858085	6	56	gly	non-glycosylated	1016:1031	arg1	A					1039:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	M9GN2-RNase and non-glycosylated RNase A	1000:1039	RESULTS HUGT1 slightly accelerated the folding of M9GN2-RNase and non-glycosylated RNase A as the same extent.
32858085	5	57	theme	RNA	935:937	arg1	substrate					939:947	the RNA substrate	931:947	the RNA substrate	931:947	Refolding was evaluated based on the RNase activity which was measured by the cleavage of the RNA substrate.
32858085	4	58	theme	human	777:781	arg1	UGGT1					783:787	human UGGT1	777:787	human UGGT1 (HUGT1)	777:795	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	4	58	theme	human	777:781	arg1	HUGT1					790:794	HUGT1	790:794	HUGT1	790:794	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	4	59	dep	M9GN-oxazoline	706:719	arg1	B					748:748	truncated RNase B	732:748	truncated RNase B	732:748	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	1	60	from	reticulum	100:108	arg1	assisted					144:151	assisted	144:151	assisted	144:151	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	1	61	theme	chaperones	189:198	arg1	action					167:172	a combined action	156:172	a combined action of enzymes and chaperones that leads them to biologically functional structures	156:252	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	1	62	gly	glycoproteins	127:139	arg1	glycoproteins					127:139	glycoproteins	127:139	glycoproteins	127:139	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	5	63	theme	substrate	939:947	arg1	cleavage					919:926	the cleavage	915:926	the cleavage of the RNA substrate	915:947	Refolding was evaluated based on the RNase activity which was measured by the cleavage of the RNA substrate.
32858085	4	64	theme	chemoenzymatic	679:692	arg1	means					694:698	chemoenzymatic means	679:698	chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B	679:748	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	5	65	theme	RNase	878:882	arg1	activity					884:891	the RNase activity	874:891	the RNase activity which was measured by the cleavage of the RNA substrate	874:947	Refolding was evaluated based on the RNase activity which was measured by the cleavage of the RNA substrate.
32858085	10	66	theme	client	1511:1516	arg1	protein					1518:1524	the client protein	1507:1524	the client protein	1507:1524	CONCLUSIONS HUGT1has the ability to promote the refolding of denatured protein and the effect would be enhanced when HUGT1 tightly interacts with the client protein via glycan recognition.
32858085	11	67	theme	glycoproteins	1707:1719	arg1	folding					1696:1702	folding	1696:1702	folding of glycoproteins	1696:1719	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	11	68	gly	glycoprotein	1750:1761	arg1	glycoprotein					1750:1761	the endoplasmic reticulum glycoprotein quality control	1724:1777	the endoplasmic reticulum glycoprotein quality control	1724:1777	GENERAL SIGNIFICANCE Our study provides a possibility that HUGT1 play a role not only in sensing the misfolded glycoprotein but also in promoting folding of glycoproteins in the endoplasmic reticulum glycoprotein quality control.
32858085	2	69	theme	essential	335:343	arg1	role					345:348	an essential role	332:348	an essential role	332:348	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	2	69	theme	essential	335:343	arg1	"					372:372	the "folding sensor"	353:372	the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins	353:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	9	70	theme	M9GN2-RNase	1348:1358	arg1	folding					1337:1343	the protein folding	1325:1343	the protein folding of M9GN2-RNase	1325:1358	Additionally, an HUGT1 mutant which lacks the glucosyltransferase activity did not accelerate the protein folding of M9GN2-RNase.
32858085	2	71	theme	glycoproteins	440:452	arg1	states					423:428	folding states	415:428	folding states of client glycoproteins	415:452	In this system, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) plays an essential role as the "folding sensor" by virtue of its ability to discriminate folding states of client glycoproteins.
32858085	1	72	from	assisted	144:151	arg1	ER					111:112	ER	111:112	ER	111:112	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	1	72	from	assisted	144:151	arg1	reticulum					100:108	the endoplasmic reticulum	84:108	the endoplasmic reticulum (ER)	84:113	BACKGROUND In the endoplasmic reticulum (ER), folding of glycoproteins is assisted by a combined action of enzymes and chaperones that leads them to biologically functional structures.
32858085	4	73	theme	modified	647:654	arg1	M9GN2-RNase					663:673	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	oligomannose-type glycan modified RNase (M9GN2-RNase)	622:674	METHODS We prepared oligomannose-type glycan modified RNase (M9GN2-RNase) by chemoenzymatic means using M9GN-oxazoline and glycan truncated RNase B and analyzed the effect of human UGGT1 (HUGT1) for refolding of the denatured M9GN2-RNase.
32858085	10	74	theme	glycan	1530:1535	arg1	recognition					1537:1547	glycan recognition	1530:1547	glycan recognition	1530:1547	CONCLUSIONS HUGT1has the ability to promote the refolding of denatured protein and the effect would be enhanced when HUGT1 tightly interacts with the client protein via glycan recognition.
33039440	6	0	theme	culture	969:975	arg1	process					977:983	cell culture process	964:983	cell culture process	964:983	This requires generation of highly enriched galactosylated variants that has been very challenging via cell culture process.
33039440	0	1	with	Generation	24:33	arg1	Glycovariants					81:93	Galactosylated Glycovariants	66:93	Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology	66:156	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	3	2	theme	wide	509:512	arg1	variety					514:520	a wide variety	507:520	a wide variety of sugars including galactose, mannose, and sialic acid	507:576	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	2	theme	wide	509:512	arg1	mannose					553:559	mannose	553:559	mannose	553:559	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	2	theme	wide	509:512	arg1	galactose					542:550	galactose	542:550	galactose	542:550	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	2	theme	wide	509:512	arg1	acid					573:576	sialic acid	566:576	sialic acid	566:576	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	2	theme	wide	509:512	arg1	sugars					525:530	sugars	525:530	sugars including galactose, mannose, and sialic acid	525:576	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	5	3	theme	galactose	763:771	arg1	role					755:758	the role	751:758	the role of galactose in antibody effector functions	751:802	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	6	4	theme	variants	920:927	arg1	generation					875:884	generation	875:884	generation of highly enriched galactosylated variants that has been very challenging via cell culture process	875:983	This requires generation of highly enriched galactosylated variants that has been very challenging via cell culture process.
33039440	1	5	theme	important	188:196	arg1	modification					217:228	an important post translational modification	185:228	an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs)	185:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	1	5	theme	important	188:196	arg1	glycosylation					168:180	N-linked glycosylation	159:180	N-linked glycosylation	159:180	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	8	6	theme	IgG	1287:1289	arg1	antibodies					1303:1312	IgG therapeutic antibodies	1287:1312	IgG therapeutic antibodies using the in-vitro glycoengineering technology	1287:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	9	7	theme	molecular	1536:1544	arg1	integrity					1546:1554	molecular integrity as demonstrated by data from an example IgG	1536:1598	molecular integrity as demonstrated by data from an example IgG	1536:1598	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	5	8	theme	research	718:725	arg1	community					727:735	the antibody research community	705:735	the antibody research community	705:735	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	6	9	theme	galactosylated	905:918	arg1	variants					920:927	highly enriched galactosylated variants	889:927	highly enriched galactosylated variants	889:927	This requires generation of highly enriched galactosylated variants that has been very challenging via cell culture process.
33039440	5	10	from	interest	693:700	arg1	community					727:735	the antibody research community	705:735	the antibody research community	705:735	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	0	11	theme	Laboratory	98:107	arg1	Scale					109:113	Laboratory Scale	98:113	Laboratory Scale Using In-Vitro Glycoengineering Technology	98:156	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	6	12	theme	enriched	896:903	arg1	variants					920:927	highly enriched galactosylated variants	889:927	highly enriched galactosylated variants	889:927	This requires generation of highly enriched galactosylated variants that has been very challenging via cell culture process.
33039440	8	13	gly	deglycosylated	1214:1227	arg1	variants					1275:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants	1214:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology	1214:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	9	14	theme	deglycosylated/hypo-galactosylated/hyper-galactosylated	1442:1496	arg1	glycovariants					1502:1514	highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants	1426:1514	highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants	1426:1514	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	1	15	theme	Fc	300:301	arg1	portion					303:309	the Fc portion	296:309	the Fc portion of monoclonal antibodies (mAbs)	296:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	0	16	theme	In-Vitro	121:128	arg1	Technology					147:156	In-Vitro Glycoengineering Technology	121:156	In-Vitro Glycoengineering Technology	121:156	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	9	17	theme	high	1522:1525	arg1	purity					1527:1532	high purity	1522:1532	high purity	1522:1532	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	9	18	theme	example	1588:1594	arg1	IgG					1596:1598	an example IgG	1585:1598	an example IgG	1585:1598	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	9	19	with	workflows	1376:1384	arg1	purity					1527:1532	high purity	1522:1532	high purity	1522:1532	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	1	20	theme	post	198:201	arg1	modification					217:228	an important post translational modification	185:228	an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs)	185:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	1	20	theme	post	198:201	arg1	glycosylation					168:180	N-linked glycosylation	159:180	N-linked glycosylation	159:180	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	8	21	theme	hyper-galactosylated	1254:1273	arg1	variants					1275:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants	1214:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology	1214:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	9	22	theme	optimized	1366:1374	arg1	workflows					1376:1384	The optimized workflows	1362:1384	The optimized workflows	1362:1384	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	7	23	theme	enriched	1082:1089	arg1	variants					1106:1113	highly enriched galactosylated variants	1075:1113	highly enriched galactosylated variants	1075:1113	To tackle this challenge, we developed a laboratory scale biochemical process to produce highly enriched galactosylated variants.
33039440	2	24	theme	mAb	344:346	arg1	glycans					351:357	mAb Fc glycans	344:357	mAb Fc glycans	344:357	mAb Fc glycans play important roles in antibody structure, stability, and function including effector function and pharmacokinetics.
33039440	1	25	theme	translational	203:215	arg1	modification					217:228	an important post translational modification	185:228	an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs)	185:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	1	25	theme	translational	203:215	arg1	glycosylation					168:180	N-linked glycosylation	159:180	N-linked glycosylation	159:180	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	0	26	theme	Detailed	2:9	arg1	Protocol					11:18	A Detailed Protocol	0:18	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.	0:157	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	6	27	theme	cell	964:967	arg1	process					977:983	cell culture process	964:983	cell culture process	964:983	This requires generation of highly enriched galactosylated variants that has been very challenging via cell culture process.
33039440	7	28	theme	galactosylated	1091:1104	arg1	variants					1106:1113	highly enriched galactosylated variants	1075:1113	highly enriched galactosylated variants	1075:1113	To tackle this challenge, we developed a laboratory scale biochemical process to produce highly enriched galactosylated variants.
33039440	8	29	theme	optimized	1143:1151	arg1	workflows					1163:1171	optimized lab-scale workflows	1143:1171	optimized lab-scale workflows	1143:1171	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	3	30	theme	sialic	566:571	arg1	acid					573:576	sialic acid	566:576	sialic acid	566:576	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	8	31	theme	antibodies	1303:1312	arg1	variants					1275:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants	1214:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology	1214:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	9	32	theme	turnaround	1398:1407	arg1	time					1409:1412	short turnaround time	1392:1412	short turnaround time	1392:1412	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	5	33	from	role	755:758	arg1	functions					794:802	antibody effector functions	776:802	antibody effector functions	776:802	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	5	34	theme	glycans	852:858	arg1	galactose					807:815	galactose	807:815	galactose	807:815	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	5	34	theme	glycans	852:858	arg1	constituent					828:838	a major constituent	820:838	a major constituent of antibody glycans	820:858	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	8	35	theme	therapeutic	1291:1301	arg1	antibodies					1303:1312	IgG therapeutic antibodies	1287:1312	IgG therapeutic antibodies using the in-vitro glycoengineering technology	1287:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	2	36	theme	effector	437:444	arg1	function					446:453	effector function	437:453	effector function	437:453	mAb Fc glycans play important roles in antibody structure, stability, and function including effector function and pharmacokinetics.
33039440	8	37	theme	deglycosylated	1214:1227	arg1	variants					1275:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants	1214:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology	1214:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	1	38	theme	monoclonal	314:323	arg1	mAbs					337:340	mAbs	337:340	mAbs	337:340	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	1	38	theme	monoclonal	314:323	arg1	antibodies					325:334	monoclonal antibodies	314:334	monoclonal antibodies (mAbs)	314:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	0	39	theme	Glycoengineering	130:145	arg1	Technology					147:156	In-Vitro Glycoengineering Technology	121:156	In-Vitro Glycoengineering Technology	121:156	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	2	40	theme	important	364:372	arg1	roles					374:378	important roles	364:378	important roles	364:378	mAb Fc glycans play important roles in antibody structure, stability, and function including effector function and pharmacokinetics.
33039440	4	41	theme	effector	623:630	arg1	functions					632:640	antibody effector functions	614:640	antibody effector functions	614:640	The role of galactose in mediating antibody effector functions is not well understood.
33039440	1	42	theme	antibodies	325:334	arg1	portion					303:309	the Fc portion	296:309	the Fc portion of monoclonal antibodies (mAbs)	296:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	1	43	from	position	284:291	arg1	portion					303:309	the Fc portion	296:309	the Fc portion of monoclonal antibodies (mAbs)	296:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	8	44	theme	glycoengineering	1333:1348	arg1	technology					1350:1359	the in-vitro glycoengineering technology	1320:1359	the in-vitro glycoengineering technology	1320:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	1	45	theme	Asparagine	245:254	arg1	residue					260:266	Asparagine 297 residue	245:266	Asparagine 297 residue	245:266	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	5	46	theme	antibody	776:783	arg1	functions					794:802	antibody effector functions	776:802	antibody effector functions	776:802	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	9	47	theme	enriched	1433:1440	arg1	glycovariants					1502:1514	highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants	1426:1514	highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants	1426:1514	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	5	48	theme	antibody	709:716	arg1	community					727:735	the antibody research community	705:735	the antibody research community	705:735	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	8	49	theme	lab-scale	1153:1161	arg1	workflows					1163:1171	optimized lab-scale workflows	1143:1171	optimized lab-scale workflows	1143:1171	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	7	50	theme	scale	1038:1042	arg1	process					1056:1062	a laboratory scale biochemical process	1025:1062	a laboratory scale biochemical process to produce highly enriched galactosylated variants	1025:1113	To tackle this challenge, we developed a laboratory scale biochemical process to produce highly enriched galactosylated variants.
33039440	9	51	from	IgG	1596:1598	arg1	data					1575:1578	data	1575:1578	data from an example IgG	1575:1598	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	3	52	theme	Fc	481:482	arg1	glycans					484:490	The Fc glycans	477:490	The Fc glycans	477:490	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	0	53	theme	Antibodies	50:59	arg1	Generation					24:33	Generation	24:33	Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology	24:156	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	8	54	theme	detailed	1177:1184	arg1	protocols					1186:1194	detailed protocols	1177:1194	detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology	1177:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	7	55	theme	biochemical	1044:1054	arg1	process					1056:1062	a laboratory scale biochemical process	1025:1062	a laboratory scale biochemical process to produce highly enriched galactosylated variants	1025:1113	To tackle this challenge, we developed a laboratory scale biochemical process to produce highly enriched galactosylated variants.
33039440	7	56	theme	laboratory	1027:1036	arg1	process					1056:1062	a laboratory scale biochemical process	1025:1062	a laboratory scale biochemical process to produce highly enriched galactosylated variants	1025:1113	To tackle this challenge, we developed a laboratory scale biochemical process to produce highly enriched galactosylated variants.
33039440	0	57	theme	Therapeutic	38:48	arg1	Antibodies					50:59	Therapeutic Antibodies	38:59	Therapeutic Antibodies	38:59	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	9	58	theme	IgG	1498:1500	arg1	glycovariants					1502:1514	highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants	1426:1514	highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants	1426:1514	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	1	59	link	N-linked	159:166	arg1	modification					217:228	an important post translational modification	185:228	an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs)	185:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	1	59	link	N-linked	159:166	arg1	glycosylation					168:180	N-linked glycosylation	159:180	N-linked glycosylation	159:180	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	8	60	theme	hypo-galactosylated	1230:1248	arg1	variants					1275:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants	1214:1282	deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology	1214:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	9	61	theme	short	1392:1396	arg1	time					1409:1412	short turnaround time	1392:1412	short turnaround time	1392:1412	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	1	62	from	residue	260:266	arg1	portion					303:309	the Fc portion	296:309	the Fc portion of monoclonal antibodies (mAbs)	296:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	9	63	dep	workflows	1376:1384	arg1	produce					1418:1424	produce	1418:1424	produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants	1418:1514	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	9	63	dep	workflows	1376:1384	arg1	offer					1386:1390	offer	1386:1390	offer short turnaround time	1386:1412	The optimized workflows offer short turnaround time and produce highly enriched deglycosylated/hypo-galactosylated/hyper-galactosylated IgG glycovariants, with high purity & molecular integrity as demonstrated by data from an example IgG.
33039440	2	64	theme	Fc	348:349	arg1	glycans					351:357	mAb Fc glycans	344:357	mAb Fc glycans	344:357	mAb Fc glycans play important roles in antibody structure, stability, and function including effector function and pharmacokinetics.
33039440	8	65	theme	in-vitro	1324:1331	arg1	technology					1350:1359	the in-vitro glycoengineering technology	1320:1359	the in-vitro glycoengineering technology	1320:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	5	66	theme	widespread	682:691	arg1	interest					693:700	widespread interest	682:700	widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans	682:858	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	0	67	from	Scale	109:113	arg1	Glycovariants					81:93	Galactosylated Glycovariants	66:93	Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology	66:156	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	1	68	theme	N-linked	159:166	arg1	modification					217:228	an important post translational modification	185:228	an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs)	185:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	1	68	theme	N-linked	159:166	arg1	glycosylation					168:180	N-linked glycosylation	159:180	N-linked glycosylation	159:180	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
33039440	8	69	theme	variants	1275:1282	arg1	generation					1200:1209	generation	1200:1209	generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology	1200:1359	In this article, we report optimized lab-scale workflows and detailed protocols for generation of deglycosylated, hypo-galactosylated and hyper-galactosylated variants of IgG therapeutic antibodies using the in-vitro glycoengineering technology.
33039440	4	70	theme	galactose	591:599	arg1	role					583:586	The role	579:586	The role of galactose in mediating antibody effector functions	579:640	The role of galactose in mediating antibody effector functions is not well understood.
33039440	0	71	theme	Galactosylated	66:79	arg1	Glycovariants					81:93	Galactosylated Glycovariants	66:93	Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology	66:156	A Detailed Protocol for Generation of Therapeutic Antibodies with Galactosylated Glycovariants at Laboratory Scale Using In-Vitro Glycoengineering Technology.
33039440	5	72	theme	antibody	843:850	arg1	glycans					852:858	antibody glycans	843:858	antibody glycans	843:858	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	5	73	theme	major	822:826	arg1	galactose					807:815	galactose	807:815	galactose	807:815	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	5	73	theme	major	822:826	arg1	constituent					828:838	a major constituent	820:838	a major constituent of antibody glycans	820:858	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	2	74	theme	antibody	383:390	arg1	structure					392:400	antibody structure	383:400	antibody structure	383:400	mAb Fc glycans play important roles in antibody structure, stability, and function including effector function and pharmacokinetics.
33039440	4	75	theme	antibody	614:621	arg1	functions					632:640	antibody effector functions	614:640	antibody effector functions	614:640	The role of galactose in mediating antibody effector functions is not well understood.
33039440	5	76	theme	effector	785:792	arg1	functions					794:802	antibody effector functions	776:802	antibody effector functions	776:802	Hence, there is widespread interest in the antibody research community to understand the role of galactose in antibody effector functions as galactose is a major constituent of antibody glycans.
33039440	3	77	theme	sugars	525:530	arg1	variety					514:520	a wide variety	507:520	a wide variety of sugars including galactose, mannose, and sialic acid	507:576	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	77	theme	sugars	525:530	arg1	mannose					553:559	mannose	553:559	mannose	553:559	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	77	theme	sugars	525:530	arg1	galactose					542:550	galactose	542:550	galactose	542:550	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	77	theme	sugars	525:530	arg1	acid					573:576	sialic acid	566:576	sialic acid	566:576	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	3	77	theme	sugars	525:530	arg1	sugars					525:530	sugars	525:530	sugars including galactose, mannose, and sialic acid	525:576	The Fc glycans are made up of a wide variety of sugars including galactose, mannose, and sialic acid.
33039440	1	78	theme	homologous	273:282	arg1	position					284:291	a homologous position	271:291	a homologous position on the Fc portion of monoclonal antibodies (mAbs)	271:341	N-linked glycosylation is an important post translational modification that occurs on Asparagine 297 residue or a homologous position on the Fc portion of monoclonal antibodies (mAbs).
34813786	5	0	theme	2,3	797:799	arg1	-linkage					801:808	α(2,3)-linkage	795:808	α(2,3)-linkage	795:808	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	0	1	link	O-linked	89:96	arg1	glycans					98:104	core 1 O-linked glycans	82:104	core 1 O-linked glycans	82:104	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	6	2	dep	cST3Gal-I	945:953	arg1	bindings					1029:1036	acceptor/donor substrate bindings	1004:1036	acceptor/donor substrate bindings	1004:1036	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	0	3	theme	core	82:85	arg1	glycans					98:104	core 1 O-linked glycans	82:104	core 1 O-linked glycans	82:104	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	6	4	theme	cST3Gal-I	945:953	arg1	identical					1048:1056	identical	1048:1056	identical	1048:1056	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	4	theme	cST3Gal-I	945:953	arg1	cST3Gal-I					945:953	cST3Gal-I	945:953	cST3Gal-I for putative acid/base catalysts	945:986	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	4	theme	cST3Gal-I	945:953	arg1	sites					936:940	The putative active sites	916:940	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings	916:1036	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	4	theme	cST3Gal-I	945:953	arg1	acid					999:1002	sialic acid	992:1002	sialic acid	992:1002	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	2	5	theme	Saccharomyces	357:369	arg1	cerevisiae					371:380	Saccharomyces cerevisiae	357:380	Saccharomyces cerevisiae	357:380	cST3Gal-I was localized to the Golgi membrane when expressed in Saccharomyces cerevisiae.
34813786	4	6	theme	core	646:649	arg1	O-glycan					653:660	core 1 O-glycan	646:660	core 1 O-glycan	646:660	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	4	6	theme	core	646:649	arg1	GalNAc					673:678	Gal β(1,3)GalNAc	663:678	Gal β(1,3)GalNAc	663:678	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	7	7	theme	vertebrate	1330:1339	arg1	enzymes					1341:1347	vertebrate enzymes	1330:1347	vertebrate enzymes	1330:1347	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	3	8	theme	Enzymatic	383:391	arg1	characterization					393:408	Enzymatic characterization	383:408	Enzymatic characterization for substrate specificity and kinetic property	383:455	Enzymatic characterization for substrate specificity and kinetic property indicate that cST3Gal-I prefers O-glycans, rather than N-glycan, of asialoglycoproteins as substrates.
34813786	7	9	theme	sialic	1304:1309	arg1	acceptor					1316:1323	its sialic acid acceptor	1300:1323	its sialic acid acceptor than vertebrate enzymes	1300:1347	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	1	10	theme	yeast	278:282	arg1	strains					284:290	yeast strains	278:290	yeast strains	278:290	An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains.
34813786	7	11	theme	C.	1244:1245	arg1	savignyi					1247:1254	C. savignyi	1244:1254	C. savignyi	1244:1254	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	3	12	theme	asialoglycoproteins	525:543	arg1	O-glycans					489:497	O-glycans	489:497	O-glycans	489:497	Enzymatic characterization for substrate specificity and kinetic property indicate that cST3Gal-I prefers O-glycans, rather than N-glycan, of asialoglycoproteins as substrates.
34813786	7	13	theme	tunicate	1223:1230	arg1	ST3Gal-I					1232:1239	an ancestral tunicate ST3Gal-I	1210:1239	an ancestral tunicate ST3Gal-I in C. savignyi	1210:1254	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	5	14	theme	blot	826:829	arg1	analysis					831:838	lectin blot analysis	819:838	lectin blot analysis with Maackia amurensis lectin	819:868	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	1	15	theme	sea	173:175	arg1	squirt					177:182	sea squirt	173:182	the sea squirt Ciona savignyi	169:197	An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains.
34813786	3	16	theme	kinetic	440:446	arg1	property					448:455	kinetic property	440:455	kinetic property	440:455	Enzymatic characterization for substrate specificity and kinetic property indicate that cST3Gal-I prefers O-glycans, rather than N-glycan, of asialoglycoproteins as substrates.
34813786	6	17	theme	putative	920:927	arg1	identical					1048:1056	identical	1048:1056	identical	1048:1056	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	17	theme	putative	920:927	arg1	cST3Gal-I					945:953	cST3Gal-I	945:953	cST3Gal-I for putative acid/base catalysts	945:986	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	17	theme	putative	920:927	arg1	sites					936:940	The putative active sites	916:940	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings	916:1036	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	17	theme	putative	920:927	arg1	acid					999:1002	sialic acid	992:1002	sialic acid	992:1002	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	5	18	theme	-linkage	801:808	arg1	formation					782:790	the formation	778:790	the formation of α(2,3)-linkage	778:808	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	1	19	theme	squirt	177:182	arg1	savignyi					190:197	the sea squirt Ciona savignyi	169:197	the sea squirt Ciona savignyi	169:197	An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains.
34813786	0	20	theme	invertebrate	7:18	arg1	sialyltransferase					20:36	Marine invertebrate sialyltransferase	0:36	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi	0:69	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	2	21	theme	Golgi	324:328	arg1	membrane					330:337	the Golgi membrane	320:337	the Golgi membrane	320:337	cST3Gal-I was localized to the Golgi membrane when expressed in Saccharomyces cerevisiae.
34813786	6	22	theme	active	929:934	arg1	identical					1048:1056	identical	1048:1056	identical	1048:1056	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	22	theme	active	929:934	arg1	cST3Gal-I					945:953	cST3Gal-I	945:953	cST3Gal-I for putative acid/base catalysts	945:986	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	22	theme	active	929:934	arg1	sites					936:940	The putative active sites	916:940	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings	916:1036	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	22	theme	active	929:934	arg1	acid					999:1002	sialic acid	992:1002	sialic acid	992:1002	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	1	23	theme	Ciona	184:188	arg1	savignyi					190:197	the sea squirt Ciona savignyi	169:197	the sea squirt Ciona savignyi	169:197	An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains.
34813786	0	24	theme	Marine	0:5	arg1	sialyltransferase					20:36	Marine invertebrate sialyltransferase	0:36	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi	0:69	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	4	25	theme	Neu5Ac	627:632	arg1	transfer					634:641	Neu5Ac transfer	627:641	Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase	627:729	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	5	26	theme	linkage-specific	877:892	arg1	treatments					904:913	linkage-specific sialidase treatments	877:913	linkage-specific sialidase treatments	877:913	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	3	27	gly	asialoglycoproteins	525:543	arg1	asialoglycoproteins					525:543	asialoglycoproteins	525:543	asialoglycoproteins as substrates	525:557	Enzymatic characterization for substrate specificity and kinetic property indicate that cST3Gal-I prefers O-glycans, rather than N-glycan, of asialoglycoproteins as substrates.
34813786	4	28	theme	human	705:709	arg1	glycosyltransferase					711:729	orthologous human glycosyltransferase	693:729	orthologous human glycosyltransferase	693:729	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	7	29	theme	ancestral	1213:1221	arg1	ST3Gal-I					1232:1239	an ancestral tunicate ST3Gal-I	1210:1239	an ancestral tunicate ST3Gal-I in C. savignyi	1210:1254	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	6	30	theme	substrate	1019:1027	arg1	bindings					1029:1036	acceptor/donor substrate bindings	1004:1036	acceptor/donor substrate bindings	1004:1036	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	5	31	theme	amurensis	853:861	arg1	lectin					863:868	Maackia amurensis lectin	845:868	Maackia amurensis lectin	845:868	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	5	32	theme	Maackia	845:851	arg1	lectin					863:868	Maackia amurensis lectin	845:868	Maackia amurensis lectin	845:868	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	6	33	theme	acceptor/donor	1004:1017	arg1	bindings					1029:1036	acceptor/donor substrate bindings	1004:1036	acceptor/donor substrate bindings	1004:1036	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	5	34	with	analysis	831:838	arg1	lectin					863:868	Maackia amurensis lectin	845:868	Maackia amurensis lectin	845:868	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	6	35	theme	enzyme	1101:1106	arg1	enzyme					1101:1106	a mammalian enzyme	1089:1106	a mammalian enzyme	1089:1106	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	35	theme	enzyme	1101:1106	arg1	residues					1077:1084	the counterpart residues	1061:1084	the counterpart residues of a mammalian enzyme, porcine ST3Gal-I	1061:1124	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	0	36	theme	sea	45:47	arg1	squirt					49:54	sea squirt	45:54	the sea squirt Ciona savignyi	41:69	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	6	37	theme	acid	999:1002	arg1	identical					1048:1056	identical	1048:1056	identical	1048:1056	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	37	theme	acid	999:1002	arg1	cST3Gal-I					945:953	cST3Gal-I	945:953	cST3Gal-I for putative acid/base catalysts	945:986	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	37	theme	acid	999:1002	arg1	sites					936:940	The putative active sites	916:940	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings	916:1036	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	37	theme	acid	999:1002	arg1	acid					999:1002	sialic acid	992:1002	sialic acid	992:1002	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	7	38	theme	acid	1311:1314	arg1	acceptor					1316:1323	its sialic acid acceptor	1300:1323	its sialic acid acceptor than vertebrate enzymes	1300:1347	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	6	39	theme	porcine	1109:1115	arg1	enzyme					1101:1106	a mammalian enzyme	1089:1106	a mammalian enzyme	1089:1106	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	39	theme	porcine	1109:1115	arg1	ST3Gal-I					1117:1124	porcine ST3Gal-I	1109:1124	porcine ST3Gal-I	1109:1124	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	40	theme	mammalian	1091:1099	arg1	enzyme					1101:1106	a mammalian enzyme	1089:1106	a mammalian enzyme	1089:1106	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	40	theme	mammalian	1091:1099	arg1	ST3Gal-I					1117:1124	porcine ST3Gal-I	1109:1124	porcine ST3Gal-I	1109:1124	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	4	41	theme	orthologous	693:703	arg1	glycosyltransferase					711:729	orthologous human glycosyltransferase	693:729	orthologous human glycosyltransferase	693:729	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	6	42	theme	sialic	992:997	arg1	acid					999:1002	sialic acid	992:1002	sialic acid	992:1002	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	43	theme	counterpart	1065:1075	arg1	enzyme					1101:1106	a mammalian enzyme	1089:1106	a mammalian enzyme	1089:1106	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	6	43	theme	counterpart	1065:1075	arg1	residues					1077:1084	the counterpart residues	1061:1084	the counterpart residues of a mammalian enzyme, porcine ST3Gal-I	1061:1124	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	0	44	theme	Ciona	56:60	arg1	savignyi					62:69	the sea squirt Ciona savignyi	41:69	the sea squirt Ciona savignyi	41:69	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	4	45	theme	C.	575:576	arg1	sialyltransferase					587:603	C. savignyi sialyltransferase	575:603	C. savignyi sialyltransferase	575:603	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	5	46	theme	lectin	819:824	arg1	analysis					831:838	lectin blot analysis	819:838	lectin blot analysis with Maackia amurensis lectin	819:868	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	7	47	from	ST3Gal-I	1232:1239	arg1	savignyi					1247:1254	C. savignyi	1244:1254	C. savignyi	1244:1254	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	1	48	theme	invertebrate	110:121	arg1	cST3Gal-I					142:150	An invertebrate sialyltransferase, cST3Gal-I	107:150	cST3Gal-I	142:150	An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains.
34813786	0	49	theme	squirt	49:54	arg1	savignyi					62:69	the sea squirt Ciona savignyi	41:69	the sea squirt Ciona savignyi	41:69	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	7	50	gly	glycoproteins	1283:1295	arg1	glycoproteins					1283:1295	glycoproteins	1283:1295	glycoproteins	1283:1295	These results could imply that an ancestral tunicate ST3Gal-I in C. savignyi would prefer O-glycan onto glycoproteins as its sialic acid acceptor than vertebrate enzymes.
34813786	1	51	theme	sialyltransferase	123:139	arg1	cST3Gal-I					142:150	An invertebrate sialyltransferase, cST3Gal-I	107:150	cST3Gal-I	142:150	An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains.
34813786	6	52	theme	acid/base	968:976	arg1	catalysts					978:986	putative acid/base catalysts	959:986	putative acid/base catalysts	959:986	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	4	53	theme	β	667:667	arg1	O-glycan					653:660	core 1 O-glycan	646:660	core 1 O-glycan	646:660	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	4	53	theme	β	667:667	arg1	GalNAc					673:678	Gal β(1,3)GalNAc	663:678	Gal β(1,3)GalNAc	663:678	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	6	54	theme	homologous	1148:1157	arg1	modeling					1169:1176	homologous structure modeling	1148:1176	homologous structure modeling	1148:1176	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	4	55	theme	Gal	663:665	arg1	O-glycan					653:660	core 1 O-glycan	646:660	core 1 O-glycan	646:660	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	4	55	theme	Gal	663:665	arg1	GalNAc					673:678	Gal β(1,3)GalNAc	663:678	Gal β(1,3)GalNAc	663:678	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	5	56	theme	α	795:795	arg1	-linkage					801:808	α(2,3)-linkage	795:808	α(2,3)-linkage	795:808	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	6	57	theme	structure	1159:1167	arg1	modeling					1169:1176	homologous structure modeling	1148:1176	homologous structure modeling	1148:1176	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	5	58	theme	sialidase	894:902	arg1	treatments					904:913	linkage-specific sialidase treatments	877:913	linkage-specific sialidase treatments	877:913	Further, it is shown that cST3Gal-I catalyzes the formation of α(2,3)-linkage, through lectin blot analysis with Maackia amurensis lectin and by linkage-specific sialidase treatments.
34813786	4	59	theme	1,3	669:671	arg1	O-glycan					653:660	core 1 O-glycan	646:660	core 1 O-glycan	646:660	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	4	59	theme	1,3	669:671	arg1	GalNAc					673:678	Gal β(1,3)GalNAc	663:678	Gal β(1,3)GalNAc	663:678	Interestingly, C. savignyi sialyltransferase exhibited effectively Neu5Ac transfer to core 1 O-glycan, Gal β(1,3)GalNAc, compared to orthologous human glycosyltransferase.
34813786	0	60	theme	savignyi	62:69	arg1	sialyltransferase					20:36	Marine invertebrate sialyltransferase	0:36	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi	0:69	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
34813786	6	61	theme	putative	959:966	arg1	catalysts					978:986	putative acid/base catalysts	959:986	putative acid/base catalysts	959:986	The putative active sites of cST3Gal-I for putative acid/base catalysts and sialic acid acceptor/donor substrate bindings were also identical to the counterpart residues of a mammalian enzyme, porcine ST3Gal-I, as predicted through homologous structure modeling.
34813786	1	62	theme	recombinant	246:256	arg1	enzyme					258:263	recombinant enzyme	246:263	recombinant enzyme expressed in yeast strains	246:290	An invertebrate sialyltransferase, cST3Gal-I, identified from the sea squirt Ciona savignyi, was functionally characterized in vitro using recombinant enzyme expressed in yeast strains.
34813786	3	63	theme	substrate	414:422	arg1	specificity					424:434	substrate specificity	414:434	substrate specificity	414:434	Enzymatic characterization for substrate specificity and kinetic property indicate that cST3Gal-I prefers O-glycans, rather than N-glycan, of asialoglycoproteins as substrates.
34813786	0	64	theme	O-linked	89:96	arg1	glycans					98:104	core 1 O-linked glycans	82:104	core 1 O-linked glycans	82:104	Marine invertebrate sialyltransferase of the sea squirt Ciona savignyi sialylated core 1 O-linked glycans.
32650974	5	0	from	α-mannosyltransferases	1065:1086	arg1	order					1095:1099	the order	1091:1099	the order of SpOch1p, SpMnn9p and SpAnp1p	1091:1131	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	4	1	theme	Spanp1+	699:705	arg1	genes					707:711	Spanp1+ genes	699:711	Spanp1+ genes	699:711	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	1	2	theme	yeast	138:142	arg1	cells					144:148	yeast cells	138:148	yeast cells	138:148	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	5	3	theme	chromatography	907:920	arg1	analysis					922:929	high-performance liquid chromatography analysis	883:929	high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	883:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	1	4	theme	cells	144:148	arg1	walls					129:133	The cell walls	120:133	The cell walls of yeast cells	120:148	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	0	5	theme	fission	79:85	arg1	yeast					87:91	the fission yeast	75:91	the fission yeast Schizosaccharomyces pombe	75:117	SpMnn9p and SpAnp1p form a protein complex involved in mannan synthesis in the fission yeast Schizosaccharomyces pombe.
32650974	1	6	link	N-linked	249:256	arg1	glycans					258:264	the N-linked glycans	245:264	the N-linked glycans	245:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	3	7	theme	fission	523:529	arg1	yeast					531:535	the fission yeast	519:535	the fission yeast Schizosaccharomyces pombe	519:561	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	4	8	theme	increased	749:757	arg1	sensitivity					759:769	an increased sensitivity	746:769	an increased sensitivity to hygromycin B, characteristic of a glycosylation defect	746:827	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	0	9	dep	yeast	87:91	arg1	pombe					113:117	Schizosaccharomyces pombe	93:117	the fission yeast Schizosaccharomyces pombe	75:117	SpMnn9p and SpAnp1p form a protein complex involved in mannan synthesis in the fission yeast Schizosaccharomyces pombe.
32650974	4	10	from	disruptions	672:682	arg1	Spmnn9+					687:693	Spmnn9+	687:693	Spmnn9+	687:693	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	4	10	from	disruptions	672:682	arg1	genes					707:711	Spanp1+ genes	699:711	Spanp1+ genes	699:711	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	1	11	theme	N-linked	249:256	arg1	glycans					258:264	the N-linked glycans	245:264	the N-linked glycans	245:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	5	12	theme	SpAnp1p	1125:1131	arg1	order					1095:1099	the order	1091:1099	the order of SpOch1p, SpMnn9p and SpAnp1p	1091:1131	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	4	13	theme	hygromycin	774:783	arg1	B					785:785	hygromycin B	774:785	hygromycin B	774:785	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	1	14	theme	large	160:164	arg1	structure					173:181	a large mannan structure	158:181	a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans	158:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	5	15	theme	acid	856:859	arg1	phosphatase					861:871	the acid phosphatase	852:871	the acid phosphatase assay	852:877	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	6	16	theme	split	1158:1162	arg1	analyses					1168:1175	split YFP analyses	1158:1175	split YFP analyses	1158:1175	Immunoprecipitation and split YFP analyses demonstrated that SpMnn9p and SpAnp1p form the M-Pol-II like complex.
32650974	1	17	link	α1,6-linked	213:223	arg1	oligomer					233:240	a linear α1,6-linked mannose oligomer	204:240	a linear α1,6-linked mannose oligomer on the N-linked glycans	204:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	5	18	theme	mannan	1001:1006	arg1	structure					1008:1016	the mannan structure	997:1016	the mannan structure in S. pombe	997:1028	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	19	from	structure	1008:1016	arg1	S. pombe					1021:1028	S. pombe	1021:1028	S. pombe	1021:1028	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	2	20	theme	polymerase	375:384	arg1	complexes					386:394	the mannan polymerase complexes M-Pol I and II	364:409	the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae	364:450	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	2	20	theme	polymerase	375:384	arg1	M-Pol					396:400	M-Pol	396:400	M-Pol	396:400	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	2	20	theme	polymerase	375:384	arg1	II					408:409	II	408:409	II	408:409	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	7	21	theme	synthesis	1333:1341	arg1	mechanism					1313:1321	the mechanism	1309:1321	the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe	1309:1376	Together, these results provided an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe.
32650974	7	22	from	mechanism	1313:1321	arg1	S. pombe					1369:1376	S. pombe	1369:1376	S. pombe	1369:1376	Together, these results provided an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe.
32650974	7	23	theme	mechanism	1313:1321	arg1	understanding					1292:1304	an improved understanding	1280:1304	an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe	1280:1376	Together, these results provided an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe.
32650974	2	24	theme	mannan	368:373	arg1	complexes					386:394	the mannan polymerase complexes M-Pol I and II	364:409	the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae	364:450	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	2	24	theme	mannan	368:373	arg1	M-Pol					396:400	M-Pol	396:400	M-Pol	396:400	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	2	24	theme	mannan	368:373	arg1	II					408:409	II	408:409	II	408:409	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	4	25	theme	slower	720:725	arg1	growth					727:732	slower growth	720:732	slower growth	720:732	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	2	26	theme	mannan	291:296	arg1	biosynthesis					271:282	The biosynthesis	267:282	The biosynthesis of the mannan	267:296	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	1	27	theme	mannan	166:171	arg1	structure					173:181	a large mannan structure	158:181	a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans	158:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	3	28	theme	S. cerevisiae	595:607	arg1	proteins					626:633	S. cerevisiae M-Pol II complex proteins	595:633	S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p	595:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	28	theme	S. cerevisiae	595:607	arg1	ScAnp1p					647:653	ScAnp1p	647:653	ScAnp1p	647:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	28	theme	S. cerevisiae	595:607	arg1	ScMnn9p					635:641	ScMnn9p	635:641	ScMnn9p	635:641	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	5	29	theme	SpMnn9p	1113:1119	arg1	order					1095:1099	the order	1091:1099	the order of SpOch1p, SpMnn9p and SpAnp1p	1091:1131	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	7	30	theme	improved	1283:1290	arg1	understanding					1292:1304	an improved understanding	1280:1304	an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe	1280:1376	Together, these results provided an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe.
32650974	5	31	theme	high-performance	883:898	arg1	chromatography					907:920	high-performance liquid chromatography	883:920	high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	883:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	0	32	theme	protein	27:33	arg1	complex					35:41	a protein complex	25:41	a protein complex involved in mannan synthesis in the fission yeast Schizosaccharomyces pombe	25:117	SpMnn9p and SpAnp1p form a protein complex involved in mannan synthesis in the fission yeast Schizosaccharomyces pombe.
32650974	5	33	theme	N-linked	934:941	arg1	glycans					943:949	N-linked glycans	934:949	N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	934:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	1	34	from	oligomer	233:240	arg1	glycans					258:264	the N-linked glycans	245:264	the N-linked glycans	245:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	0	35	from	synthesis	62:70	arg1	yeast					87:91	the fission yeast	75:91	the fission yeast Schizosaccharomyces pombe	75:117	SpMnn9p and SpAnp1p form a protein complex involved in mannan synthesis in the fission yeast Schizosaccharomyces pombe.
32650974	4	36	theme	glycosylation	808:820	arg1	defect					822:827	a glycosylation defect	806:827	a glycosylation defect	806:827	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	5	37	dep	Spmnn9Δ	954:960	arg1	mutants					974:980	mutants	974:980	mutants	974:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	3	38	theme	proteins	626:633	arg1	homologs					583:590	homologs	583:590	homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p	583:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	38	theme	proteins	626:633	arg1	proteins					570:577	these proteins	564:577	these proteins	564:577	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	7	39	from	synthesis	1333:1341	arg1	S. pombe					1369:1376	S. pombe	1369:1376	S. pombe	1369:1376	Together, these results provided an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe.
32650974	2	40	theme	cerevisiae	441:450	arg1	Golgi					418:422	the Golgi	414:422	the Golgi of Saccharomyces cerevisiae	414:450	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	1	41	contain	possess	150:156	arg2	structure					173:181	a large mannan structure	158:181	a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans	158:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	1	41	contain	possess	150:156	arg1	walls					129:133	The cell walls	120:133	The cell walls of yeast cells	120:148	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	6	42	theme	YFP	1164:1166	arg1	analyses					1168:1175	split YFP analyses	1158:1175	split YFP analyses	1158:1175	Immunoprecipitation and split YFP analyses demonstrated that SpMnn9p and SpAnp1p form the M-Pol-II like complex.
32650974	3	43	dep	yeast	531:535	arg1	pombe					557:561	Schizosaccharomyces pombe	537:561	the fission yeast Schizosaccharomyces pombe	519:561	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	4	44	theme	defect	822:827	arg1	characteristic					788:801	characteristic	788:801	characteristic	788:801	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	2	45	from	complexes	386:394	arg1	Golgi					418:422	the Golgi	414:422	the Golgi of Saccharomyces cerevisiae	414:450	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	2	46	theme	ScOch1p	314:320	arg1	α1,6-mannosyltransfease					322:344	ScOch1p α1,6-mannosyltransfease	314:344	ScOch1p α1,6-mannosyltransfease	314:344	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	5	47	from	Spanp1Δ	966:972	arg1	analysis					922:929	high-performance liquid chromatography analysis	883:929	high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	883:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	47	from	Spanp1Δ	966:972	arg1	assay					873:877	the acid phosphatase assay	852:877	the acid phosphatase assay	852:877	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	4	48	theme	characteristic	788:801	arg1	B					785:785	hygromycin B	774:785	hygromycin B	774:785	Cells harboring disruptions in Spmnn9+ and Spanp1+ genes showed slower growth at 37°C and an increased sensitivity to hygromycin B, characteristic of a glycosylation defect.
32650974	5	49	from	glycans	943:949	arg1	Spanp1Δ					966:972	Spanp1Δ	966:972	Spanp1Δ	966:972	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	49	from	glycans	943:949	arg1	Spmnn9Δ					954:960	Spmnn9Δ	954:960	Spmnn9Δ	954:960	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	50	from	analysis	922:929	arg1	Spanp1Δ					966:972	Spanp1Δ	966:972	Spanp1Δ	966:972	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	50	from	analysis	922:929	arg1	Spmnn9Δ					954:960	Spmnn9Δ	954:960	Spmnn9Δ	954:960	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	51	theme	glycans	943:949	arg1	analysis					922:929	high-performance liquid chromatography analysis	883:929	high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	883:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	51	theme	glycans	943:949	arg1	assay					873:877	the acid phosphatase assay	852:877	the acid phosphatase assay	852:877	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	3	52	dep	proteins	626:633	arg1	proteins					626:633	S. cerevisiae M-Pol II complex proteins	595:633	S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p	595:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	52	dep	proteins	626:633	arg1	ScAnp1p					647:653	ScAnp1p	647:653	ScAnp1p	647:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	52	dep	proteins	626:633	arg1	ScMnn9p					635:641	ScMnn9p	635:641	ScMnn9p	635:641	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	5	53	link	N-linked	934:941	arg1	glycans					943:949	N-linked glycans	934:949	N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	934:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	7	54	theme	mannan	1326:1331	arg1	synthesis					1333:1341	mannan synthesis	1326:1341	mannan synthesis by SpMnn9p and SpAnp1p in S. pombe	1326:1376	Together, these results provided an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe.
32650974	3	55	theme	complex	618:624	arg1	proteins					626:633	S. cerevisiae M-Pol II complex proteins	595:633	S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p	595:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	55	theme	complex	618:624	arg1	ScAnp1p					647:653	ScAnp1p	647:653	ScAnp1p	647:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	55	theme	complex	618:624	arg1	ScMnn9p					635:641	ScMnn9p	635:641	ScMnn9p	635:641	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	5	56	from	assay	873:877	arg1	Spanp1Δ					966:972	Spanp1Δ	966:972	Spanp1Δ	966:972	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	56	from	assay	873:877	arg1	Spmnn9Δ					954:960	Spmnn9Δ	954:960	Spmnn9Δ	954:960	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	1	57	theme	cell	124:127	arg1	walls					129:133	The cell walls	120:133	The cell walls of yeast cells	120:148	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	5	58	from	Spmnn9Δ	954:960	arg1	analysis					922:929	high-performance liquid chromatography analysis	883:929	high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	883:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	5	58	from	Spmnn9Δ	954:960	arg1	assay					873:877	the acid phosphatase assay	852:877	the acid phosphatase assay	852:877	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	1	59	theme	linear	206:211	arg1	oligomer					233:240	a linear α1,6-linked mannose oligomer	204:240	a linear α1,6-linked mannose oligomer on the N-linked glycans	204:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	0	60	theme	mannan	55:60	arg1	synthesis					62:70	mannan synthesis	55:70	mannan synthesis in the fission yeast Schizosaccharomyces pombe	55:117	SpMnn9p and SpAnp1p form a protein complex involved in mannan synthesis in the fission yeast Schizosaccharomyces pombe.
32650974	2	61	dep	complexes	386:394	arg1	complexes					386:394	the mannan polymerase complexes M-Pol I and II	364:409	the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae	364:450	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	2	61	dep	complexes	386:394	arg1	M-Pol					396:400	M-Pol	396:400	M-Pol	396:400	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	2	61	dep	complexes	386:394	arg1	II					408:409	II	408:409	II	408:409	The biosynthesis of the mannan is initiated by ScOch1p α1,6-mannosyltransfease, and elongated by the mannan polymerase complexes M-Pol I and II in the Golgi of Saccharomyces cerevisiae.
32650974	3	62	theme	SpAnp1	500:505	arg1	proteins					507:514	SpAnp1 proteins	500:514	SpAnp1 proteins	500:514	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	5	63	theme	phosphatase	861:871	arg1	assay					873:877	the acid phosphatase assay	852:877	the acid phosphatase assay	852:877	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	1	64	theme	α1,6-linked	213:223	arg1	oligomer					233:240	a linear α1,6-linked mannose oligomer	204:240	a linear α1,6-linked mannose oligomer on the N-linked glycans	204:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
32650974	3	65	theme	M-Pol	609:613	arg1	proteins					626:633	S. cerevisiae M-Pol II complex proteins	595:633	S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p	595:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	65	theme	M-Pol	609:613	arg1	ScAnp1p					647:653	ScAnp1p	647:653	ScAnp1p	647:653	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	3	65	theme	M-Pol	609:613	arg1	ScMnn9p					635:641	ScMnn9p	635:641	ScMnn9p	635:641	Here, we functionally characterized SpMnn9 and SpAnp1 proteins in the fission yeast Schizosaccharomyces pombe; these proteins are homologs of S. cerevisiae M-Pol II complex proteins ScMnn9p and ScAnp1p.
32650974	7	66	from	S. pombe	1369:1376	arg1	mechanism					1313:1321	the mechanism	1309:1321	the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe	1309:1376	Together, these results provided an improved understanding of the mechanism of mannan synthesis by SpMnn9p and SpAnp1p in S. pombe.
32650974	5	67	theme	liquid	900:905	arg1	chromatography					907:920	high-performance liquid chromatography	883:920	high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants	883:980	Results obtained from the acid phosphatase assay and high-performance liquid chromatography analysis of N-linked glycans in Spmnn9Δ and Spanp1Δ mutants suggested that the mannan structure in S. pombe is synthesized sequentially by the α-mannosyltransferases in the order of SpOch1p, SpMnn9p and SpAnp1p.
32650974	1	68	theme	mannose	225:231	arg1	oligomer					233:240	a linear α1,6-linked mannose oligomer	204:240	a linear α1,6-linked mannose oligomer on the N-linked glycans	204:264	The cell walls of yeast cells possess a large mannan structure mainly comprising of a linear α1,6-linked mannose oligomer on the N-linked glycans.
33435207	6	0	theme	second	1210:1215	arg1	it					1194:1195	it	1194:1195	it	1194:1195	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	0	theme	second	1210:1215	arg1	protein					1230:1236	the second three-domain protein	1206:1236	the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis	1206:1289	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	1	theme	three-domain	1217:1228	arg1	it					1194:1195	it	1194:1195	it	1194:1195	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	1	theme	three-domain	1217:1228	arg1	protein					1230:1236	the second three-domain protein	1206:1236	the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis	1206:1289	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	1	2	theme	N-linked	165:172	arg1	glycans					174:180	the four N-linked glycans	156:180	the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein	156:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	7	3	theme	canonical	1385:1393	arg1	pathway					1442:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	1	4	theme	other	261:265	arg1	glycans					267:273	any other glycans	257:273	any other glycans	257:273	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	7	5	theme	endoplasmic	1400:1410	arg1	pathway					1442:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	6	6	theme	glycan	1274:1279	arg1	synthesis					1281:1289	glycan synthesis	1274:1289	glycan synthesis	1274:1289	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	1	7	theme	glycans	174:180	arg1	structures					142:151	The structures	138:151	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein	138:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	3	8	with	glycosyltransferase	657:675	arg1	acids					732:736	approximately 300 amino acids	708:736	approximately 300 amino acids	708:736	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	3	8	with	glycosyltransferase	657:675	arg1	domains					697:703	three putative domains	682:703	three putative domains of approximately 300 amino acids each	682:741	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	6	9	theme	responsible	1044:1054	arg1	A111/114R					1012:1020	A111/114R	1012:1020	A111/114R	1012:1020	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	9	theme	responsible	1044:1054	arg1	protein					1029:1035	the protein	1025:1035	the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan	1025:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	10	theme	complex	1142:1148	arg1	glycan					1150:1155	this complex glycan	1137:1155	this complex glycan	1137:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	11	theme	region	1127:1132	arg1	residues					1106:1113	the five conserved residues	1087:1113	the five conserved residues of the core region of this complex glycan	1087:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	11	theme	region	1127:1132	arg1	region					1127:1132	the core region	1118:1132	the core region of this complex glycan	1118:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	7	12	theme	additional	1328:1337	arg1	support					1339:1345	additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins	1328:1483	additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins	1328:1483	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	7	13	theme	independent	1522:1532	arg1	glycosylation					1508:1520	glycosylation	1508:1520	glycosylation independent of cellular organelles using virus-encoded enzymes	1508:1583	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	6	14	theme	conserved	1096:1104	arg1	residues					1106:1113	the five conserved residues	1087:1113	the five conserved residues of the core region of this complex glycan	1087:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	14	theme	conserved	1096:1104	arg1	region					1127:1132	the core region	1118:1132	the core region of this complex glycan	1118:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	4	15	theme	hydrolytic	831:840	arg1	activity					842:849	the hydrolytic activity	827:849	the hydrolytic activity of protein A111/114R	827:870	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	6	16	theme	core	1122:1125	arg1	region					1127:1132	the core region	1118:1132	the core region of this complex glycan	1118:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	0	17	theme	N-Glycans	127:135	arg1	Synthesis					105:113	the Synthesis	101:113	the Synthesis of Atypical N-Glycans	101:135	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	7	18	theme	host	1395:1398	arg1	pathway					1442:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	0	19	contain	Has	49:51	arg2	Functions					79:87	Three Glycosyltransferase Functions	53:87	Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans	53:135	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	0	19	contain	Has	49:51	arg1	A111/114R					39:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	2	20	theme	unique	373:378	arg1	core					405:408	a unique conserved central glycan core	371:408	a unique conserved central glycan core consisting of five sugars	371:434	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	2	21	theme	central	390:396	arg1	core					405:408	a unique conserved central glycan core	371:408	a unique conserved central glycan core consisting of five sugars	371:434	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	0	22	theme	Atypical	118:125	arg1	N-Glycans					127:135	Atypical N-Glycans	118:135	Atypical N-Glycans	118:135	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	4	23	theme	protein	797:803	arg1	modeling					805:812	protein modeling	797:812	protein modeling	797:812	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	1	24	from	structures	142:151	arg1	protein					233:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	2	25	theme	conserved	380:388	arg1	core					405:408	a unique conserved central glycan core	371:408	a unique conserved central glycan core consisting of five sugars	371:434	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	0	26	theme	PBCV-1	12:17	arg1	A111/114R					39:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	3	27	theme	putative	688:695	arg1	acids					732:736	approximately 300 amino acids	708:736	approximately 300 amino acids	708:736	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	3	27	theme	putative	688:695	arg1	domains					697:703	three putative domains	682:703	three putative domains of approximately 300 amino acids each	682:741	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	6	28	theme	residues	1106:1113	arg1	residues					1106:1113	the five conserved residues	1087:1113	the five conserved residues of the core region of this complex glycan	1087:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	28	theme	residues	1106:1113	arg1	three					1078:1082	three	1078:1082	three	1078:1082	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	6	28	theme	residues	1106:1113	arg1	region					1127:1132	the core region	1118:1132	the core region of this complex glycan	1118:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	1	29	theme	prototype	191:199	arg1	protein					233:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	0	30	theme	Chlorovirus	0:10	arg1	A111/114R					39:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	3	31	theme	amino	726:730	arg1	acids					732:736	approximately 300 amino acids	708:736	approximately 300 amino acids	708:736	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	2	32	theme	known	309:313	arg1	chloroviruses					315:327	All known chloroviruses	305:327	All known chloroviruses	305:327	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	1	33	theme	chlorovirus	201:211	arg1	protein					233:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	0	34	theme	Protein	31:37	arg1	A111/114R					39:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	3	35	theme	acids	732:736	arg1	acids					732:736	approximately 300 amino acids	708:736	approximately 300 amino acids	708:736	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	3	35	theme	acids	732:736	arg1	domains					697:703	three putative domains	682:703	three putative domains of approximately 300 amino acids each	682:741	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	1	36	link	N-linked	165:172	arg1	glycans					174:180	the four N-linked glycans	156:180	the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein	156:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	1	37	theme	PBCV-1	213:218	arg1	protein					233:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	0	38	theme	Multidomain	19:29	arg1	A111/114R					39:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R	0:47	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	3	39	theme	genetic	529:535	arg1	analyses					552:559	genetic and structural analyses	529:559	genetic and structural analyses	529:559	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	1	40	theme	major	220:224	arg1	protein					233:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	2	41	theme	virus	465:469	arg1	P1L6					471:474	antigenic mutant virus P1L6	448:474	antigenic mutant virus P1L6	448:474	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	1	42	theme	life	299:302	arg1	life					299:302	life	299:302	life	299:302	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	1	42	theme	life	299:302	arg1	domains					288:294	the three domains	278:294	the three domains of life	278:302	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	4	43	theme	sequence	775:782	arg1	analysis					784:791	in silico sequence analysis	765:791	in silico sequence analysis	765:791	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	1	44	theme	capsid	226:231	arg1	protein					233:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	the prototype chlorovirus PBCV-1 major capsid protein	187:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	2	45	theme	mutant	458:463	arg1	P1L6					471:474	antigenic mutant virus P1L6	448:474	antigenic mutant virus P1L6	448:474	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	2	46	theme	sugars	504:509	arg1	sugars					504:509	the five sugars	495:509	the five sugars	495:509	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	2	46	theme	sugars	504:509	arg1	four					487:490	four	487:490	four	487:490	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	3	47	theme	gene	604:607	arg1	a111/114r					609:617	PBCV-1 gene a111/114r	597:617	PBCV-1 gene a111/114r	597:617	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	2	48	theme	glycan	398:403	arg1	core					405:408	a unique conserved central glycan core	371:408	a unique conserved central glycan core consisting of five sugars	371:434	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	0	49	theme	Glycosyltransferase	59:77	arg1	Functions					79:87	Three Glycosyltransferase Functions	53:87	Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans	53:135	Chlorovirus PBCV-1 Multidomain Protein A111/114R Has Three Glycosyltransferase Functions Involved in the Synthesis of Atypical N-Glycans.
33435207	4	50	theme	protein	854:860	arg1	A111/114R					862:870	protein A111/114R	854:870	protein A111/114R	854:870	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	3	51	theme	analyses	552:559	arg1	combination					514:524	A combination	512:524	A combination of genetic and structural analyses	512:559	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	1	52	from	protein	233:239	arg1	structures					142:151	The structures	138:151	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein	138:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	1	52	from	protein	233:239	arg1	glycans					174:180	the four N-linked glycans	156:180	the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein	156:239	The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life.
33435207	4	53	dep	in	765:766	arg1	silico					768:773	silico	768:773	silico	768:773	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	3	54	dep	domains	697:703	arg1	each					738:741	each	738:741	each	738:741	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	4	55	dep	analysis	784:791	arg1	addition					753:760	addition	753:760	addition	753:760	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	6	56	theme	three	1078:1082	arg1	attachment					1064:1073	the attachment	1060:1073	the attachment of three of the five conserved residues of the core region of this complex glycan	1060:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	7	57	gly	glycoproteins	1471:1483	arg1	glycoproteins					1471:1483	their glycoproteins	1465:1483	their glycoproteins	1465:1483	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	6	58	theme	glycan	1150:1155	arg1	region					1127:1132	the core region	1118:1132	the core region of this complex glycan	1118:1155	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	2	59	contain	has	483:485	arg2	sugars					504:509	the five sugars	495:509	the five sugars	495:509	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	2	59	contain	has	483:485	arg1	P1L6					471:474	antigenic mutant virus P1L6	448:474	antigenic mutant virus P1L6	448:474	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	2	59	contain	has	483:485	arg2	four					487:490	four	487:490	four	487:490	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	2	60	theme	antigenic	333:341	arg1	variants					343:350	antigenic variants	333:350	antigenic variants (or mutants)	333:363	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	2	60	theme	antigenic	333:341	arg1	mutants					356:362	mutants	356:362	mutants	356:362	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	4	61	theme	A111/114R	862:870	arg1	activity					842:849	the hydrolytic activity	827:849	the hydrolytic activity of protein A111/114R	827:870	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	3	62	theme	PBCV-1	597:602	arg1	a111/114r					609:617	PBCV-1 gene a111/114r	597:617	PBCV-1 gene a111/114r	597:617	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	7	63	gly	glycosylate	1453:1463	arg1	glycoproteins					1471:1483	their glycoproteins	1465:1483	their glycoproteins	1465:1483	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	7	64	theme	virus-encoded	1563:1575	arg1	enzymes					1577:1583	virus-encoded enzymes	1563:1583	virus-encoded enzymes	1563:1583	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	6	65	dep	corroborated	1180:1191	arg1	if					1163:1164	if	1163:1164	if	1163:1164	Thus, A111/114R is the protein likely responsible for the attachment of three of the five conserved residues of the core region of this complex glycan, and, if biochemically corroborated, it would be the second three-domain protein coded by PBCV-1 that is involved in glycan synthesis.
33435207	4	66	theme	in	765:766	arg1	analysis					784:791	in silico sequence analysis	765:791	in silico sequence analysis	765:791	Here, in addition to in silico sequence analysis and protein modeling, we measured the hydrolytic activity of protein A111/114R.
33435207	7	67	theme	reticulum-Golgi	1412:1426	arg1	pathway					1442:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	7	68	theme	cellular	1537:1544	arg1	organelles					1546:1555	cellular organelles	1537:1555	cellular organelles using virus-encoded enzymes	1537:1583	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	2	69	theme	antigenic	448:456	arg1	P1L6					471:474	antigenic mutant virus P1L6	448:474	antigenic mutant virus P1L6	448:474	All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars.
33435207	7	70	theme	glycosylation	1428:1440	arg1	pathway					1442:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	the canonical host endoplasmic reticulum-Golgi glycosylation pathway	1381:1448	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
33435207	3	71	theme	structural	541:550	arg1	analyses					552:559	genetic and structural analyses	529:559	genetic and structural analyses	529:559	A combination of genetic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each.
33435207	7	72	theme	organelles	1546:1555	arg1	independent					1522:1532	independent	1522:1532	independent	1522:1532	Importantly, these findings provide additional support that the chloroviruses do not use the canonical host endoplasmic reticulum-Golgi glycosylation pathway to glycosylate their glycoproteins; instead, they perform glycosylation independent of cellular organelles using virus-encoded enzymes.
32784866	2	0	theme	clot	344:347	arg1	strength					349:356	increased clot strength	334:356	increased clot strength	334:356	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	7	1	theme	peritoneum	1533:1542	arg1	utilization					1518:1528	utilization	1518:1528	utilization of peritoneum for dialysis	1518:1555	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	2	theme	membrane	1483:1490	arg1	damage					1492:1497	peritoneal membrane damage	1472:1497	peritoneal membrane damage	1472:1497	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	3	3	theme	lectin	645:650	arg1	blotting					652:659	lectin blotting	645:659	lectin blotting	645:659	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	2	4	theme	increased	334:342	arg1	strength					349:356	increased clot strength	334:356	increased clot strength	334:356	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	0	5	theme	Peritoneal	89:98	arg1	Dialysis					100:107	Peritoneal Dialysis	89:107	Peritoneal Dialysis	89:107	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	4	6	theme	FA2	771:773	arg1	glycan					775:780	FA2 glycan	771:780	FA2 glycan	771:780	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	3	7	from	patients	496:503	arg1	plasma					484:489	the plasma	480:489	the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD)	480:546	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	4	8	theme	decreased	751:759	arg1	levels					761:766	decreased levels	751:766	decreased levels of FA2 glycan	751:780	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	6	9	theme	dialysis	1114:1121	arg1	solutions					1123:1131	dialysis solutions	1114:1131	dialysis solutions	1114:1131	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	5	10	from	glycans	803:809	arg1	chains					825:830	individual chains	814:830	individual chains	814:830	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	7	11	located	observed	1350:1357	arg2	complications					1336:1348	fibrinogen-related complications	1317:1348	fibrinogen-related complications observed in ESRD-PD patients	1317:1377	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	11	located	observed	1350:1357	arg1	patients					1370:1377	ESRD-PD patients	1362:1377	ESRD-PD patients	1362:1377	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	5	12	dep	fibrinogen	912:921	arg1	such					924:927	such	924:927	such	924:927	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	6	13	from	increase	1145:1152	arg1	levels					1174:1179	the fucosylation levels	1157:1179	the fucosylation levels	1157:1179	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	7	14	theme	peritoneal	1472:1481	arg1	damage					1492:1497	peritoneal membrane damage	1472:1497	peritoneal membrane damage	1472:1497	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	4	15	contain	had	717:719	arg2	levels					761:766	decreased levels	751:766	decreased levels of FA2 glycan	751:780	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	4	15	contain	had	717:719	arg2	levels					731:736	increased levels	721:736	increased levels of A2BG2	721:745	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	4	15	contain	had	717:719	arg1	fibrinogen					692:701	fibrinogen	692:701	fibrinogen from patients	692:715	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	3	16	from	ESRD	510:513	arg1	dialysis					529:536	peritoneal dialysis	518:536	peritoneal dialysis (ESRD-PD)	518:546	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	3	16	from	ESRD	510:513	arg1	ESRD-PD					539:545	ESRD-PD	539:545	ESRD-PD	539:545	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	5	17	theme	platelet	948:955	arg1	aggregation					957:967	platelet aggregation	948:967	platelet aggregation	948:967	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	6	18	theme	N-glycans	1046:1054	arg1	levels					1020:1025	Increased levels	1010:1025	Increased levels of multi-antennary N-glycans in ESRD-PD patients	1010:1074	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	6	19	theme	ESRD-PD	1059:1065	arg1	patients					1067:1074	ESRD-PD patients	1059:1074	ESRD-PD patients	1059:1074	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	0	20	from	Marker	40:45	arg1	Patients					77:84	Patients	77:84	Patients on Peritoneal Dialysis	77:107	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	0	20	from	Marker	40:45	arg1	Dialysis					100:107	Peritoneal Dialysis	89:107	Peritoneal Dialysis	89:107	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	6	21	theme	solutions	1123:1131	arg1	type					1106:1109	the type	1102:1109	the type of dialysis solutions	1102:1131	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	3	22	theme	peritoneal	518:527	arg1	dialysis					529:536	peritoneal dialysis	518:536	peritoneal dialysis (ESRD-PD)	518:546	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	3	22	theme	peritoneal	518:527	arg1	ESRD-PD					539:545	ESRD-PD	539:545	ESRD-PD	539:545	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	2	23	theme	cloth	371:375	arg1	lysis					377:381	delayed cloth lysis	363:381	delayed cloth lysis	363:381	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	7	24	theme	glycans	1279:1285	arg1	investigation					1251:1263	investigation	1251:1263	investigation of fibrinogen glycans	1251:1285	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	5	25	theme	fibrinogen	912:921	arg1	functions					899:907	physiological functions	885:907	physiological functions of fibrinogen (such as coagulation and platelet aggregation)	885:968	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	7	26	theme	better	1297:1302	arg1	insight					1304:1310	better insight	1297:1310	better insight into fibrinogen-related complications observed in ESRD-PD patients	1297:1377	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	2	27	theme	delayed	363:369	arg1	lysis					377:381	delayed cloth lysis	363:381	delayed cloth lysis	363:381	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	2	28	with	patients	229:236	arg1	disease					259:265	end-stage renal disease	243:265	end-stage renal disease (ESRD)	243:272	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	2	28	with	patients	229:236	arg1	ESRD					268:271	ESRD	268:271	ESRD	268:271	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	6	29	theme	membrane	1220:1227	arg1	damage					1229:1234	the peritoneal membrane damage	1205:1234	the peritoneal membrane damage	1205:1234	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	4	30	theme	increased	721:729	arg1	levels					731:736	increased levels	721:736	increased levels of A2BG2	721:745	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	3	31	with	patients	496:503	arg1	ESRD					510:513	ESRD	510:513	ESRD on peritoneal dialysis (ESRD-PD)	510:546	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	5	32	theme	glycans	803:809	arg1	distribution					787:798	The distribution	783:798	The distribution of glycans on individual chains	783:830	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	7	33	dep	offer	1291:1295	arg1	contribute					1398:1407	contribute	1398:1407	contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis	1398:1555	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	6	34	from	levels	1020:1025	arg1	patients					1067:1074	ESRD-PD patients	1059:1074	ESRD-PD patients	1059:1074	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	4	35	theme	A2BG2	741:745	arg1	levels					761:766	decreased levels	751:766	decreased levels of FA2 glycan	751:780	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	4	35	theme	A2BG2	741:745	arg1	levels					731:736	increased levels	721:736	increased levels of A2BG2	721:745	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	6	36	theme	peritoneal	1209:1218	arg1	damage					1229:1234	the peritoneal membrane damage	1205:1234	the peritoneal membrane damage	1205:1234	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	5	37	theme	individual	814:823	arg1	chains					825:830	individual chains	814:830	individual chains	814:830	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	0	38	from	Patients	77:84	arg1	Dialysis					100:107	Peritoneal Dialysis	89:107	Peritoneal Dialysis	89:107	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	5	39	theme	responsible	869:879	arg1	chain					862:866	the γ chain	856:866	the γ chain	856:866	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	4	40	theme	healthy	674:680	arg1	controls					682:689	healthy controls	674:689	healthy controls	674:689	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	7	41	theme	fibrinogen	1268:1277	arg1	glycans					1279:1285	fibrinogen glycans	1268:1285	fibrinogen glycans	1268:1285	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	2	42	theme	high	179:182	arg1	risk					184:187	A high risk	177:187	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD)	177:272	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	2	43	theme	end-stage	243:251	arg1	disease					259:265	end-stage renal disease	243:265	end-stage renal disease (ESRD)	243:272	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	2	43	theme	end-stage	243:251	arg1	ESRD					268:271	ESRD	268:271	ESRD	268:271	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	6	44	theme	multi-antennary	1030:1044	arg1	N-glycans					1046:1054	multi-antennary N-glycans	1030:1054	multi-antennary N-glycans	1030:1054	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	3	45	gly	glycosylation	562:574	arg1	fibrinogen					586:595	native fibrinogen	579:595	native fibrinogen	579:595	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	3	45	gly	glycosylation	562:574	arg1	subunits					605:612	its subunits	601:612	its subunits	601:612	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	0	46	theme	Prognostic	29:38	arg1	Marker					40:45	a Prognostic Marker	27:45	a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis	27:107	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	7	47	theme	fibrinogen-related	1317:1334	arg1	complications					1336:1348	fibrinogen-related complications	1317:1348	fibrinogen-related complications observed in ESRD-PD patients	1317:1377	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	3	48	theme	native	579:584	arg1	fibrinogen					586:595	native fibrinogen	579:595	native fibrinogen	579:595	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	0	49	theme	End-Stage	50:58	arg1	Disease					66:72	End-Stage Renal Disease	50:72	End-Stage Renal Disease	50:72	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	5	50	theme	γ	860:860	arg1	chain					862:866	the γ chain	856:866	the γ chain	856:866	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	3	51	theme	lectin-based	617:628	arg1	microarray					630:639	lectin-based microarray	617:639	lectin-based microarray	617:639	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	5	52	from	distribution	787:798	arg1	chains					825:830	individual chains	814:830	individual chains	814:830	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	7	53	theme	damage	1492:1497	arg1	prognosis					1412:1420	prognosis	1412:1420	prognosis	1412:1420	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	53	theme	damage	1492:1497	arg1	determination					1455:1467	determination	1455:1467	determination of peritoneal membrane damage	1455:1497	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	53	theme	damage	1492:1497	arg1	choice					1423:1428	choice	1423:1428	choice of personalised therapy	1423:1452	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	53	theme	damage	1492:1497	arg1	length					1508:1513	the length	1504:1513	the length of utilization of peritoneum for dialysis	1504:1555	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	2	54	theme	complications	207:219	arg1	risk					184:187	A high risk	177:187	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD)	177:272	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	7	55	theme	personalised	1433:1444	arg1	therapy					1446:1452	personalised therapy	1433:1452	personalised therapy	1433:1452	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	5	56	theme	physiological	885:897	arg1	functions					899:907	physiological functions	885:907	physiological functions of fibrinogen (such as coagulation and platelet aggregation)	885:968	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	6	57	theme	fucosylation	1161:1172	arg1	levels					1174:1179	the fucosylation levels	1157:1179	the fucosylation levels	1157:1179	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.
32784866	0	58	from	Dialysis	100:107	arg1	Marker					40:45	a Prognostic Marker	27:45	a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis	27:107	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	4	59	theme	glycan	775:780	arg1	levels					761:766	decreased levels	751:766	decreased levels of FA2 glycan	751:780	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	4	59	theme	glycan	775:780	arg1	levels					731:736	increased levels	721:736	increased levels of A2BG2	721:745	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	5	60	from	chains	825:830	arg1	distribution					787:798	The distribution	783:798	The distribution of glycans on individual chains	783:830	The distribution of glycans on individual chains was also affected, with the γ chain, responsible for physiological functions of fibrinogen (such as coagulation and platelet aggregation), being most prone to these alterations.
32784866	2	61	theme	clot	318:321	arg1	formation					323:331	delayed clot formation	310:331	delayed clot formation	310:331	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	4	62	from	patients	708:715	arg1	fibrinogen					692:701	fibrinogen	692:701	fibrinogen from patients	692:715	Compared to healthy controls, fibrinogen from patients had increased levels of A2BG2 and decreased levels of FA2 glycan.
32784866	2	63	theme	cardiovascular	192:205	arg1	complications					207:219	cardiovascular complications	192:219	cardiovascular complications	192:219	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	3	64	theme	subunits	605:612	arg1	glycosylation					562:574	glycosylation	562:574	glycosylation of native fibrinogen and its subunits	562:612	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	2	65	theme	delayed	310:316	arg1	formation					323:331	delayed clot formation	310:331	delayed clot formation	310:331	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	0	66	theme	Disease	66:72	arg1	Marker					40:45	a Prognostic Marker	27:45	a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis	27:107	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	7	67	theme	therapy	1446:1452	arg1	prognosis					1412:1420	prognosis	1412:1420	prognosis	1412:1420	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	67	theme	therapy	1446:1452	arg1	determination					1455:1467	determination	1455:1467	determination of peritoneal membrane damage	1455:1497	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	67	theme	therapy	1446:1452	arg1	choice					1423:1428	choice	1423:1428	choice of personalised therapy	1423:1452	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	67	theme	therapy	1446:1452	arg1	length					1508:1513	the length	1504:1513	the length of utilization of peritoneum for dialysis	1504:1555	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	3	68	theme	fibrinogen	586:595	arg1	glycosylation					562:574	glycosylation	562:574	glycosylation of native fibrinogen and its subunits	562:612	Taking into consideration that fibrinogen mediates these processes, we isolated fibrinogen from the plasma from patients with ESRD on peritoneal dialysis (ESRD-PD), and examined glycosylation of native fibrinogen and its subunits by lectin-based microarray and lectin blotting.
32784866	1	69	theme	protein	144:150	arg1	structure					152:160	protein structure	144:160	protein structure	144:160	Glycosylation may strongly affect protein structure and functions.
32784866	0	70	theme	Renal	60:64	arg1	Disease					66:72	End-Stage Renal Disease	50:72	End-Stage Renal Disease	50:72	Fibrinogen Fucosylation as a Prognostic Marker of End-Stage Renal Disease in Patients on Peritoneal Dialysis.
32784866	7	71	theme	ESRD-PD	1362:1368	arg1	patients					1370:1377	ESRD-PD patients	1362:1377	ESRD-PD patients	1362:1377	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	2	72	theme	renal	253:257	arg1	disease					259:265	end-stage renal disease	243:265	end-stage renal disease (ESRD)	243:272	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	2	72	theme	renal	253:257	arg1	ESRD					268:271	ESRD	268:271	ESRD	268:271	A high risk of cardiovascular complications seen in patients with end-stage renal disease (ESRD) is, at least partly associated with delayed clot formation, increased clot strength, and delayed cloth lysis.
32784866	7	73	theme	utilization	1518:1528	arg1	prognosis					1412:1420	prognosis	1412:1420	prognosis	1412:1420	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	73	theme	utilization	1518:1528	arg1	determination					1455:1467	determination	1455:1467	determination of peritoneal membrane damage	1455:1497	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	73	theme	utilization	1518:1528	arg1	choice					1423:1428	choice	1423:1428	choice of personalised therapy	1423:1452	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	7	73	theme	utilization	1518:1528	arg1	length					1508:1513	the length	1504:1513	the length of utilization of peritoneum for dialysis	1504:1555	Consequently, investigation of fibrinogen glycans can offer better insight into fibrinogen-related complications observed in ESRD-PD patients and, additionally, contribute to prognosis, choice of personalised therapy, determination of peritoneal membrane damage, and the length of utilization of peritoneum for dialysis.
32784866	6	74	theme	Increased	1010:1018	arg1	levels					1020:1025	Increased levels	1010:1025	Increased levels of multi-antennary N-glycans in ESRD-PD patients	1010:1074	Increased levels of multi-antennary N-glycans in ESRD-PD patients were also associated with the type of dialysis solutions, whereas an increase in the fucosylation levels was strongly related to the peritoneal membrane damage.